UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 10-K

(Mark One)

☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the Fiscal Year Ended December 31, ~~2024~~2025

☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

Commission File Number 001-36019

TONIX PHARMACEUTICALS HOLDING CORP.

(Exact name of registrant as specified in its charter)

Nevada		26-1434750
(State or other jurisdiction of incorporation or organization)		(IRS Employer Identification No.)
26 Main Street, Suite 101 Chatham, New Jersey		07928
200 Connell Drive, Suite 3100 Berkeley Heights, New Jersey		07928
(Address of principal executive office)		(Zip Code)
(862) 799-8599 (Registrant’s telephone number, including area code)

Securities registered pursuant to Section 12(b) of the Act:

Title of each class		Trading Symbol		Name of each exchange on which registered
Common Stock, $0.001 par value		TNXP		The NASDAQ Stock Market LLC

Securities registered pursuant to Section 12(g) of the Act: None

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined by Rule 405 of the Securities Act. Yes ☐ No ☒

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. Yes ☐ No ☒

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate by check mark whether the registrant has submitted electronically, if any, every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 229.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☒ No ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and an “emerging growth company” in Rule 12b-2 of the Exchange Act

Large accelerated filer ☐	Accelerated filer ☐
Non-accelerated filer ☒	Smaller reporting company ☒
	Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒

The aggregate market value of the voting common equity held by non-affiliates as of June 30, ~~2024~~2025, based on the closing sales price of the common stock as quoted on The NASDAQ ~~Global~~Stock Market was $6271,~~857~~370,~~126~~839. For purposes of this computation, all officers and ~~directors~~ directors are deemed to be affiliates. ~~Such determination should not be deemed an admission that such directors, officers, or 5 percent beneficial owners are, in fact, affiliates of the registrant.~~

As of March 1711, ~~2025~~2026, there were 613,~~434~~405,~~881~~401 shares of registrant’s common stock outstanding.

DOCUMENTS INCORPORATED BY REFERENCE

None.

TABLE OF CONTENTS

		PAGE
PART I
Item 1.	Business	3
Item 1A.	Risk Factors	6559
Item 1B.	Unresolved Staff Comments	9884
Item 1C.	Cybersecurity Disclosures	9885
Item 2.	Properties	9985
Item 3.	Legal Proceedings	9986
Item 4.	Mine Safety Disclosures	9986
PART II
Item 5.	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	~~100~~86
Item 6.	Reserved	~~100~~87
Item 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	~~101~~88
Item 7A.	Quantitative and Qualitative Disclosures about Market Risk	~~114~~93
Item 8.	Financial Statements and Supplementary Data	F-1 – F-3529
Item 9.	Changes in and Disagreements with Accountants on Accounting and Financial Disclosures	~~115~~99
Item 9A.	Controls and Procedures	~~115~~99
Item 9B.	Other Information	~~116~~100
Item 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	~~116~~100
PART III
Item 10.	Directors, Executive Officers and Corporate Governance	~~117~~101
Item 11.	Executive Compensation	~~125~~108
Item 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	~~135~~117
Item 13.	Certain Relationships and Related Transactions, and Director Independence	~~136~~118
Item 14.	Principal Accounting Fees and Services	~~137~~119
PART IV
Item 15.	Exhibits, Financial Statement Schedules	~~138~~120
	Signatures	~~144~~126

PART I

ITEM 1 – BUSINESS

This Annual Report on Form 10-K (including the section regarding Management’s Discussion and Analysis of Financial Condition ~~and~~ and Results of Operations) contains forward-looking statements regarding our business, financial condition, results of operations ~~and~~ and prospects. All statements contained in this Annual Report other than statements of historical fact, including, but not limited to, statements regarding the launch and commercialization of TONMYA and our migraine products, our future results of operations and financial position, business strategy, market size, potential growth opportunities, clinical and nonclinical development activities, efficacy and safety profile of our marketed products and product candidates, potential therapeutic benefits and economic value of TONMYA™, our migraine products and our product candidates, our ability to market and sell our products while maintaining full compliance with applicable federal and state laws, rules and regulations, the timing and results of nonclinical studies and clinical trials, the potential impact of global business or macroeconomic conditions, including as a result of inflation, changing interest rates, cybersecurity incidents, significant political, trade or regulatory developments and global regional conflicts on our operations, and the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates. Words such as “expects,” “anticipates,” “intends,” “plans,” “believes,” “seeks,” “estimates” and similar expressions or variations of such words are intended to identify forward-looking statements, but are not deemed to represent an all-inclusive means of identifying forward-looking statements as denoted in this Annual Report on Form 10-K. Additionally, statements concerning future matters are forward-looking statements.

Although forward-looking statements in this Annual Report on Form 10-K reflect the good faith judgment of our ~~Management~~management, such statements can only be based on facts and factors currently known by us. Consequently, forward-looking statements are inherently subject to risks and uncertainties and actual results and outcomes may differ materially from the results and outcomes discussed in or anticipated by the forward-looking statements. Factors that could cause or contribute to such differences in results and outcomes include, without limitation, those specifically addressed under the heading “Risks Factors” below, as well as those discussed elsewhere in this Annual Report on Form 10-K. Readers are urged not to place undue reliance on these forward-looking statements, which speak only as of the date of this Annual Report on Form 10-K. We file reports with the Securities and Exchange Commission (“SEC”). You can read and copy any materials we file or will file with the SEC, which, among other places, can be found on the SEC’s website at http://www.sec.gov, as well as on our corporate website at www.tonixpharma.com).

We undertake no obligation to revise or update any forward-looking statements in order to reflect any event or circumstance that may arise after the date of this Annual Report on Form 10-K. Readers are urged to carefully review and consider the various disclosures made throughout the entirety of this Annual Report, which attempt to advise interested parties of the risks and factors that may affect our business, financial condition, results of operations and prospects.

Forward-looking statements include, but are not necessarily limited to, those relating to:

● Our prospects are dependent on the success of TNX 102-SL for the management of Fibromyalgia (“FM”) and progressing our pipeline through development stages. To the extent regulatory approval of TNX-102 SL is delayed or not granted or, if approved, TNX-102 SL is not commercially successful, our business, financial condition and results of operations may be materially adversely affected and the price of our common stock may decline.

● The commercial success and market acceptance of our products, including the coverage of our products by payors and pharmacy benefit managers; our ability to successfully develop and execute our sales, marketing and non-personal and digital promotion strategies, including developing and maintaining relationships with customers, physicians, payors and other constituencies, the entry of other products competitive with our commercial products;

● Our ability to successfully execute business development, strategic partnerships, and investment opportunities to build and grow for the future;

● Our ability to achieve the expected financial performance from our marketed products Tosymra® and Zembrace® Symtouch®, as well as delays, challenges and expenses, and unexpected costs associated with integrating and operating this commercial business;

● The ability of our third-party manufacturers to manufacture adequate quantities of commercially saleable inventory and active pharmaceutical ingredients for each of our products, and our ability to maintain our supply chain;

● Our ability to raise additional capital, if necessary;

● The timing and results of any future research and development efforts including potential clinical studies relating to any future product candidates;

● Our common stock maintaining compliance with Nasdaq’s minimum closing bid requirement of at least $1.00 per share.

Business Overview

~~Tonix~~We ~~Pharmaceuticals~~ (“Tonix” or the “Company”) is are a fully-integrated biopharmaceutical company ~~developing~~commercializing and ~~commercializing~~developing ~~therapeutics~~innovative totherapies ~~treat,~~for ~~and~~central ~~vaccines~~nervous tosystem ~~prevent,~~(“CNS”) ~~disease~~disorders, ~~and~~immunology, ~~alleviate~~infectious ~~suffering.~~diseases, ~~Tonix’s~~and ~~primary~~rare ~~focus~~diseases. isOur toportfolio ~~obtain~~consists ~~U.S.~~of ~~marketing~~commercial, ~~authorization~~development ~~for~~and ~~TNX~~discovery-~~102~~stage SLprograms. ~~(cyclobenzaprine HCl sublingual~~In ~~tablet)~~August ~~5.6~~2025, mgwe (2received xapproval ~~2.8 mg tablets) for the management of fibromyalgia (“FM”)~~ from the U.S. Food and Drug Administration (“FDA”)~~. The~~ ~~FDA~~for ~~assigned~~TONMYA afor ~~prescription~~the ~~drug~~treatment ~~user~~of ~~fee~~fibromyalgia in ~~act~~adults. ~~(“PDUFA”)~~TONMYA ~~goal~~is ~~date~~our offirst ~~August~~internally ~~15,~~developed ~~2025,~~product ~~for~~to areceive ~~decision~~FDA onapproval. ~~marketing~~We ~~authorization for~~hold ~~TNX-102~~worldwide ~~SL.~~commercialization Inrights ~~addition~~to TONMYA, wea ~~market~~centrally ~~two~~acting, ~~FDA~~non-~~approved,~~opioid ~~prescription~~analgesic ~~products~~designed for ~~the~~bedtime ~~treatment~~administration ~~of acute migraine,~~ and welong-term ~~are developing a robust pipeline of potential new products~~use.

~~Our~~We ~~pipeline~~launched ~~has~~TONMYA™ ~~been~~(cyclobenzaprine ~~generated~~HCl ~~from~~sublingual ~~internal~~tablets) ~~discovery, as well as licenses,~~for ~~acquisitions~~the ~~and~~treatment ~~collaborations~~of ~~with~~fibromyalgia ~~academic~~in ~~institutions~~adults ~~and non-profit organizations. Our development portfolio is focused~~ on ~~central nervous~~November ~~system (“CNS”)~~17, ~~disorders,~~2025. ~~but~~TONMYA ~~also~~is ~~consists~~the offirst ~~immunology,~~new ~~infectious~~medicine ~~disease~~for ~~and~~fibromyalgia ~~rare~~in ~~disease,~~more ~~product~~than ~~candidates~~15 years. ~~The~~In ~~CNS~~addition ~~portfolio includes small molecules and biologics~~ to ~~treat pain~~TONMYA, ~~neurologic,~~we ~~psychiatric~~market ~~and~~two ~~addiction conditions and includes TNX~~FDA-~~1300~~approved ~~which~~prescription isproducts infor ~~Phase~~the 2treatment ~~clinical~~of ~~development~~acute tomigraine: ~~treat~~Zembrace® ~~cocaine~~SymTouch® (sumatriptan ~~intoxication~~injection) ~~partially~~and ~~funded~~Tosymra® by(sumatriptan ~~the~~nasal ~~U.S. National Institute on Drug Abuse (NIDA~~spray). Our ~~immunology~~commercial ~~portfolio~~platform includes ~~TNX-1500 (anti-CD40L monoclonal antibody~~sales, ~~or mAb)~~marketing, amarket ~~biologic which has shown encouraging~~access, ~~results in Phase 1~~distribution, ~~which~~and wepatient ~~plan~~support tocapabilities. ~~study~~We tohave ~~prevent~~generated ~~organ~~a ~~transplant~~diversified ~~rejection~~pipeline ~~and~~of ~~treat~~development ~~autoimmune~~candidates ~~diseases.~~through ~~Our~~internal ~~infectious disease~~discovery, ~~portfolio includes TNX~~in-~~801~~licensing, ~~(horsepox~~acquisitions, ~~live~~and ~~virus~~collaborations ~~vaccine)~~with, acommercial, ~~vaccine~~academic ~~in development to prevent smallpox~~ and ~~mpox~~non-profit ~~(formerly~~institutions. ~~known~~With ascommercial ~~monkeypox)~~operations established and ~~TNX-4200, which is~~ a ~~discovery program for~~ broad ~~spectrum~~development ~~antiviral~~portfolio, ~~drugs~~our ~~funded~~strategy byis ~~a U.S Department of Defense contract for up~~ to ~~$34~~ ~~million~~grow ~~over~~TONMYA ~~five~~into ~~years.~~a ~~TNX-4200~~leading istherapy ~~being~~for ~~developed~~fibromyalgia, atadvance ~~our~~pipeline ~~R&D facility located in Frederick~~programs, ~~Maryland, (“RDC”),~~ ~~which~~and ~~has~~pursue ~~biosafety~~strategic ~~level~~business ~~2 (BSL-2) with BSL-3 components. Tonix’s product~~ development ~~candidates are investigational new drugs or biologics and have not been approved for any indication~~opportunities.

~~Central Nervous~~Our ~~System~~development ~~(CNS)~~pipeline ~~Pipeline~~includes multiple programs in clinical and preclinical development.

InThe ~~October~~proprietary ~~2024,~~cyclobenzaprine ~~Tonix~~HCl ~~submitted~~sublingual atablet ~~New~~formulation contained ~~Drug~~in ~~Application~~TONMYA ~~(“NDA”)~~is referred to ~~the~~as ~~FDA for~~ “TNX-102 SL” ~~5.6~~outside mgof ~~for~~ the ~~management~~fibromyalgia ofindication. ~~FM,~~We aare ~~proprietary~~exploring ~~sublingual~~the ~~tablet~~utility ~~formulation~~ of ~~cyclobenzaprine~~TNX-102 SL (~~“CBP”)~~cyclobenzaprine ~~designed~~HCl ~~for~~sublingual ~~bedtime~~tablets) ~~administration,~~in ~~and~~Phase in2 ~~December~~clinical ~~2024,~~trials ~~the~~for ~~FDA~~major ~~assigned~~depressive adisorder ~~PDUFA~~(“MDD”) ~~goal~~and ~~date~~acute ofstress ~~August~~disorder ~~15,~~(“ASD”) ~~2025,~~and ~~for~~acute astress ~~decision~~reaction on(“ASR”). ~~marketing authorization for~~ TNX-102 SL. FM is abeing ~~chronic~~developed ~~pain~~to ~~disorder~~treat ~~characterized~~ASR byand ~~widespread~~ASD ~~pain,~~under an ~~non~~Investigator-~~restorative~~Initiated ~~sleep,~~investigational ~~fatigue~~new ~~and~~drug ~~impaired~~application ~~cognition.~~(“IND”) ~~TNX-102~~at SLthe isUniversity aof ~~centrally-acting,~~North ~~non-opioid~~Carolina ~~analgesic designed for long-term bedtime~~(“UNC”) ~~use~~in ~~and~~the ~~has~~ongoing ~~been~~OASIS ~~studied~~study infor ~~three~~which ~~Phase~~UNC 3received ~~trials~~funding ~~using~~from ~~TNX-102~~the ~~SL 5~~U.6S. ~~mg,~~Department ~~two~~of ~~studies~~Defense ~~reported~~(“DoD”). ~~statistically~~A ~~significant~~Phase ~~results.~~2 ~~The FDA~~study ~~granted~~ of TNX-102 SL ~~Fast~~for ~~Track~~MDD ~~designation~~is inexpected ~~July~~to ~~2024.~~commence Wemid-2026 ~~are~~under ~~preparing for~~ a ~~commercial~~Tonix ~~launch~~IND ofthat ~~TNX-102~~has SLbeen incleared by the ~~fourth quarter of 2025, conditional on~~ FDA ~~approval~~.

~~In March~~Our ~~2024,~~clinical ~~Tonix~~stage ~~announced it selected two contract manufacturing organizations (CMOs), one of which is Almac Pharma Services,~~programs aalso ~~member of the privately owned Almac Group, as dual supply sources for the potential launch and commercialization of TNX-102 SL in the U.S.~~include:

●

Prevention of Lyme Disease: TNX-4800 (anti-OspA from Borrelia burgdorferi), a monoclonal antibody for seasonal prevention of Lyme disease, for which initiation of a Phase 2 field study is planned for the first half of 2027 and of a Phase 2 human challenge study for 2028, pending FDA clearances.

●

Prevention of Kidney Transplant Rejection/Treatment of Autoimmune Diseases: TNX-1500, a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154), which is Phase 2-ready and being developed for the prevention of kidney transplant rejection and for which an investigator-initiated Phase 2 study in kidney transplant is expected to initiate in mid-2026. TNX-1500 is also in development for the treatment of autoimmune diseases.

●

Treatment of Cocaine Intoxication: TNX-1300, a double-mutant cocaine esterase, which is in Phase 2 for the treatment of cocaine intoxication. TNX-1300 has been granted Breakthrough Therapy designation by the FDA.

●

Treatment of Prader-Willi Syndrome: TNX-2900, intranasal oxytocin potentiated with magnesium, in development for Prader-Willi syndrome and initiation of a Phase 2 study is planned for the first quarter of 2027. TNX-2900 has been granted Orphan Drug designation and Rare Pediatric Disease designation.

●

Treatment of Acute Stress Disorder and Acute Stress Reaction: TNX 102-SL – Collaboration with University of North Carolina, Investigator-initiated IND, currently enrolling Phase 2 study.

●

Treatment of Major Depressive Disorder: TNX 102-SL – Planning to initiate a potentially pivotal Phase 2 study mid-2026.

Our pre-clinical programs include:

●

Vaccine for Protection against mpox and smallpox: TNX-801 (horsepox, live virus vaccine) for mpox and smallpox. TNX-801 is expected to enter a Phase 1 study in 2027 pending FDA clearance. TNX-801 is in the pre-IND stages of development.

●

Broad Spectrum Anti-viral to protect against viral diseases: TNX-4200, a small molecule broad-spectrum antiviral agent targeting CD45 for the prevention or treatment of high lethality infections to improve the medical readiness of military personnel in biological threat environments. The TNX-4200 program is supported by an up to $34 million contract over five years from the DoD’s Defense Threat Reduction Agency (“DTRA”). TNX-4200 is in the pre-IND stages of development.

●

Treatment of gastric and colorectal cancer: TNX-1700, a fusion protein of TFF2 and albumin, is in preclinical development for the treatment of gastric and colorectal cancer in combination with PD-1 blockade, in-licensed from Columbia University. TNX-1700 is in the pre-IND stages of development.

●

Non-opioid analgesic for neuropathic pain: TNX-4900, a highly selective small-molecule Sigma-1 receptor (“S1R”) antagonist, for neuropathic pain, in the pre-IND stages of development.

With commercial operations established and a broad development portfolio advancing, our strategy is to grow TONMYA into a leading therapy for fibromyalgia, advance pipeline programs, and pursue strategic business development opportunities.

Our commercial portfolio of FDA-approved medicines includes:

TONMYA (cyclobenzaprine HCl sublingual tablets) – Fibromyalgia

TONMYA, a proprietary sublingual formulation of cyclobenzaprine designed for bedtime dosing and long-term use, is approved in the United States for the treatment of fibromyalgia in adults and was launched in November 2025. TONMYA was approved under the 505(b)(2) pathway based on three Phase 3 studies, including two studies that demonstrated statistically significant improvement in pain compared with placebo. Clinical studies showed rapid onset of benefit, sustained efficacy, and a safety profile consistent with known cyclobenzaprine effects, with the most common adverse events being transient local oral reactions.

~~TNX-102~~TONMYA SLis ~~also~~designed to target the non-restorative sleep that we believe is ~~being~~central ~~developed~~to ~~also~~fibromyalgia aspathophysiology. aTONMYA’s ~~treatment~~sublingual formulation is designed for ~~acute~~transmucosal ~~stress~~delivery ~~reaction~~to ~~(“ASR”)~~bypass ~~and~~first-pass tohepatic ~~prevent~~metabolism, ~~acute~~which ~~stress~~reduces ~~disorder~~formation of norcyclobenzaprine, ~~(“ASD”)~~the ~~and~~persistent ~~posttraumatic~~active ~~stress~~metabolite ~~disorder~~that ~~(“PTSD”)~~we ~~under~~believe ainterferes ~~physician-initiated~~with ~~Investigational~~the ~~New~~duration ~~Drug~~of any treatment effects from oral, swallowed cyclobenzaprine. ~~Application~~The ~~(“IND”)~~sublingual, transmucosal formulation results in ~~partnership~~a distinct pharmacokinetic profile compared to oral cyclobenzaprine, with greater ~~the~~relative ~~University~~bioavailability of ~~North~~the ~~Carolina~~parent ~~(“UNC”)~~drug ~~Institute~~and ~~for~~reduced ~~Trauma Recovery.~~active metabolite exposure during sleep.

InWe ~~addition,~~commercialize ~~TNX-102~~TONMYA SLthrough our ~~has~~sales ~~active~~organization, ~~INDs~~which ~~for~~includes ~~the~~an ~~treatment~~internal ofsales ~~PTSD~~force, ~~agitation~~and ~~in Alzheimer’s~~a ~~disease~~contracted ~~(“AAD”)~~salesforce, ~~alcohol~~non-personal ~~use~~promotion, ~~disorder~~digital ~~(“AUD”)~~engagement, market ~~and~~access ~~the~~programs, ~~management~~patient ofsupport ~~multi-site~~services, ~~pain~~and ~~associated with~~distribution ~~Long~~through ~~COVID~~national ~~(also~~wholesalers ~~known~~and asspecialty ~~Post-Acute SARS-CoV-2 or PASC)~~distributors. ~~TNX-102~~We SLare ~~for~~focused on ~~AAD~~obtaining ~~has~~payer ~~been~~coverage, ~~granted~~building ~~Fast~~physician ~~Track~~awareness, ~~designation~~and bydriving ~~the~~adoption ~~FDA. We~~primarily ~~are~~in ~~currently~~practices ~~not~~that ~~actively~~have ~~studying~~a ~~TNX-102~~history SLof indiagnosing and ~~PTSD~~treating fibromyalgia, ~~AAD~~which orincludes ~~AUD.~~rheumatology, ~~Tonix~~primary iscare, ~~continuously~~pain ~~evaluating~~management ~~further~~and ~~indications~~neurology ~~for which TNX-102 SL could potentially provide benefit~~practices.

~~Another CNS~~We ~~candidate~~have incontracted ~~development is TNX-1300 (double-mutant cocaine esterase) which is in Phase 2~~ for ~~the~~two ~~treatment~~commercial ofsupply ~~cocaine~~sources intoxication. TNX-1300 has been granted Breakthrough Therapy designation by the FDA. TNX-1300 was licensed from Columbia University in 2019 after a Phase 2 study showed that it rapidly and efficiently disintegrates cocaine in the blood of ~~volunteers~~TONMYA, ~~who~~one ~~received intravenous (i.v.)~~of ~~cocaine.~~which Inis ~~August~~Almac ofPharma ~~2022~~Services, ~~we received~~ a ~~Federal~~member ~~Grant from the U.S. National Institute on Drug Abuse (“NIDA”) a part~~ of the ~~U.S.~~privately ~~National~~owned ~~Institutes~~Almac ~~of Health (“NIH”) to advance the development of TNX-1300 as a treatment for cocaine intoxication~~Group.

~~Finally,~~We we are ~~developing~~pursuing ~~TNX-1900~~lifecycle ~~(intranasal~~management ~~potentiated~~strategies ~~oxytocin)~~ for ~~several~~TONMYA, ~~CNS~~including ~~disorders~~potential label ~~through~~expansion, ~~investigator~~real-~~initiated~~world ~~studies.~~evidence ~~TNX-1900 is in development through investigator-initiated studies at Massachusetts General Hospital (“MGH”) for the treatment of binge eating disorder (“BED”)~~generation, ~~adolescent obesity,~~ and ~~bone~~geographic ~~health in pediatric autism~~expansion. ~~TNX-1900 is in development through an investigator-initiated study at the University of Washington for the treatment of social anxiety disorder.~~

~~Immunology~~Zembrace® ~~Pipeline~~SymTouch® (sumatriptan injection) and Tosymra® (sumatriptan nasal spray) - Migraine Franchise

~~Our~~Zembrace SymTouch ~~lead~~(sumatriptan ~~candidate~~injection) in3 ~~the~~mg ~~immunology pipeline~~ is ~~TNX-1500,~~a ~~an Fc~~low-~~modified~~dose ~~humanized monoclonal~~autoinjector ~~antibody~~designed ~~(“mAb”),~~for ~~directed~~ease ~~against~~of ~~CD40-ligand~~use ~~(CD40L,~~and ~~also~~rapid ~~known~~onset asof ~~CD154)~~action. ~~TNX-1500~~Zembrace is ~~was~~the ~~engineered~~only tobranded ~~modulate binding~~sumatriptan toautoinjector Fcactively ~~receptors~~promoted ~~with~~in the ~~goal~~United ofStates ~~maintaining~~and ~~the~~has ~~activity~~patent ofprotection ~~first-generation~~into ~~mAbs,~~2036. ~~yet~~Tosymra (sumatriptan ~~with~~nasal ~~reduced~~spray) ~~risk~~10 ofmg ~~thrombotic complications. TNX-1500~~ is ~~being~~a ~~developed~~rapid-acting tointranasal ~~prevent~~formulation ~~organ~~using ~~transplant~~Intravail® ~~rejection~~permeation asenhancer ~~well~~technology with aspatent toprotection ~~treat~~into ~~autoimmune conditions~~2031. ~~Topline~~Effective ~~results~~January ~~from a Phase~~ 1, ~~single ascending dose escalation study at 3 mg/kg~~2026, 10Tosymra ~~mg/kg~~has ~~and~~preferred 30exclusive ~~mg/kg~~placement ofon ~~TNX-1500~~a inpayer ~~healthy~~formulary ~~volunteers~~representing approximately ~~was~~16 ~~reported~~million incovered ~~the first quarter of 2025~~lives.

Zembrace SymTouch and Tosymra are both indicated for the treatment of acute migraine with or without aura in adults. Zembrace SymTouch is the only branded sumatriptan autoinjector professionally promoted in the United States and is designed for ease of use and favorable tolerability with a low 3 mg dose. Tosymra is a novel intranasal sumatriptan product formulated with a permeation enhancer that provides rapid and efficient absorption of sumatriptan. Tosymra was approved on the basis of bioequivalence to subcutaneous (s.c.) sumatriptan. Tonix Medicines is the only manufacturer with both a branded injectable and nasal spray indicated for the acute treatment of migraine with or without aura in adults.

Development Pipeline

Central Nervous System

In September 2025, we announced the successful completion of a Type B Pre-IND meeting with the FDA regarding the development of TNX-102 SL for the treatment of MDD. We received positive feedback from the FDA and plan to pursue a supplemental new drug application (“sNDA”) to expand the therapeutic indication of TNX-102 SL to include MDD, based on exploratory findings suggesting that improving sleep quality may positively impact depressive symptoms.

In November 2025, we announced the FDA cleared the IND application to support clinical development of TNX-102 SL 5.6 mg for the treatment of MDD in adults. The unique pharmacological profile of TNX-102 SL is designed to target the disturbed sleep which is often associated with depression. Prior studies of TNX-102 SL in fibromyalgia and post-traumatic stress disorder (“PTSD”) showed promising signals for improvement of depressive symptoms on the Beck Depression Inventory-II and the Montgomery-Åsberg Depression Rating Scale (“MADRS”), respectively.

The IND clearance enables Tonix to proceed with a potentially pivotal Phase 2 HORIZON study, a 6-week, randomized, double-blind, placebo-controlled study of TNX-102 SL as a first-line monotherapy in adults with MDD. About 360 patients will be enrolled at approximately 30 U.S. sites. Eligible participants are 18 years or older and currently experiencing a moderate to severe major depressive episode. The study will compare TNX-102 SL 5.6 mg, taken sublingually at bedtime, to placebo, with the primary endpoint being the MADRS total score change from baseline at Week 6. Secondary endpoints include global impression scores, anxiety ratings, and measures of sleep disturbance. We plan to initiate enrollment of the study in mid-year 2026.

TNX-~~1500~~102 ~~has~~SL also ~~been studied in combination with other immunosuppressive agents in allogeneic transplants in non-human primates at MGH. In experiments at MGH, TNX-1500~~ is being developed ~~studied~~ as ~~monotherapy~~a ortreatment infor ~~combination with~~ASR ~~other immunosuppressive agents in heart~~ and ~~kidney~~ASD ~~allogeneic~~under ~~organ~~an ~~transplants in non~~investigator-~~human~~initiated ~~primates.~~IND ~~Results~~with ~~from experiments in kidney and heart transplants indicate that TNX-1500 appears to have comparable efficacy to historical experiments using~~ the ~~chimeric~~University ~~mouse/human IgG1 version (5c8H1)~~ of ~~the~~North ~~anti-CD40L~~Carolina ~~mAb~~Institute ~~5c8~~for Trauma Recovery.

In addition, TNX-~~1500~~102 ~~also~~SL ishas ~~being~~active ~~studied~~INDs infor ~~combination~~the ~~with~~treatment ~~other~~of ~~immunosuppressive agents~~PTSD, inagitation ~~xenogeneic organ transplants~~ in ~~non-human~~Alzheimer’s ~~primates~~disease ~~at MGH. In some of these studies~~(“AAD”), ~~genetically~~alcohol use ~~engineered~~disorder (“GEAUD”) ~~pigs~~ inand ~~baboon~~the ~~transplants~~management ~~were~~of ~~treated~~multi-site ~~with~~pain ~~cold~~associated ~~perfused~~with ~~ischemia~~Long ~~minimization~~COVID ~~and~~(also aknown ~~novel~~as coPost-~~stimulation-based~~Acute ~~immunosuppressive regimen~~SARS-CoV-2 ~~including~~or PASC). TNX-~~1500.~~102 ~~The~~SL ~~results~~for ofAAD ~~these~~has ~~preclinical~~been ~~studies~~granted ~~were~~Fast ~~encouraging~~Track ~~and~~designation ~~demonstrated~~by the ~~potential of GE pig hearts in the context of a clinically applicable regimen~~FDA. ~~The~~We ~~multi-GE~~are ~~pigs~~currently ~~were~~not ~~provided~~actively bystudying ~~eGenesis and Revivicor. Revivicor is a subsidiary of United Therapeutics.~~TNX-102 ~~Some~~SL ~~results from the collaboration with MGH and eGenesis were published~~ in ~~the peer-reviewed journal~~PTSD, ~~Nature in 2023. In March of 2024~~AAD, ~~MGH~~Long ~~announced~~COVID ~~the~~or ~~first GE pig kidney transplant into a living recipient supported in part by the pre-clinical work with TNX-1500. Subsequently~~AUD, ~~several~~and ~~other~~are GEcontinuously ~~pig~~evaluating ~~kidney~~further ~~transplants~~indications ~~have~~for ~~been~~which ~~performed.~~ TNX-~~1500~~102 ~~treatment~~SL ~~has~~could ~~not been used in any human transplant~~potentially ~~recipient~~provide benefit.

~~Our immunology~~We ~~pipeline~~are also ~~includes~~developing TNX-~~1700,~~1300 ~~a recombinant Trefoil Factor Family 2~~ (~~“hTFF2~~double-~~HSA”)~~mutant ~~fusion~~cocaine ~~protein~~esterase), ~~that~~which ~~was~~is ~~licensed~~in ~~from~~Phase ~~Columbia~~2 ~~University~~for inthe ~~2019~~treatment of cocaine intoxication. TNX-~~1700~~1300 ~~consists~~has ofbeen ~~TFF2~~granted ~~fused~~Breakthrough toTherapy ~~human~~designation ~~serum~~by ~~albumin~~the ~~and~~FDA. isTNX-1300 was alicensed ~~biologic being~~from ~~developed~~Columbia toUniversity ~~treat~~in ~~gastric~~2019 ~~and~~after ~~colorectal~~a ~~cancers~~Phase by2 anstudy ~~immune-oncology~~showed ~~mechanism,~~that init ~~combination~~rapidly ~~with~~and ~~PD1~~efficiently ~~blockers,~~disintegrates ~~and is~~cocaine in the blood ~~preclinical~~of ~~stage~~volunteers ofwho ~~development.~~received Weintravenous ~~presented~~(i.v.) ~~data~~cocaine. ~~that~~We ~~show~~received a ~~murine~~Federal ~~version~~Grant offrom ~~TNX-1700~~the ~~consisting~~U.S. ofNational aInstitute ~~fusion~~on ~~protein~~Drug ~~with~~Abuse ~~murine~~(“NIDA”), ~~serum~~a ~~albumin~~part ~~was~~of ~~able~~the toU.S. ~~evoke~~National ~~anti-tumor~~Institutes ~~immunity~~of inHealth ~~the~~(“NIH”), ~~MC38~~to ~~mouse~~advance ~~model~~the development of ~~colorectal~~TNX-1300 as ~~cancer~~a astreatment ~~monotherapy~~for ~~and that~~cocaine ~~TNX-1700~~intoxication, ~~augmented~~and the ~~efficacy~~funding ofperiod ~~anti-PD1~~is ~~therapy~~now incompleted. ~~both~~Because of the ~~MC38~~challenges ~~model~~of ~~and~~recruiting ~~the~~eligible ~~CT26.wt~~patients into ~~mouse~~a ~~models~~Phase of2 ~~colorectal~~study, ~~cancer. We plan~~we toterminated ~~request~~that anstudy ~~INTERACT~~and ~~meeting~~intend to meet with the FDA in ~~2025~~2026 to ~~seek~~inform ~~early~~the ~~guidance~~clinical ondesign ~~program~~of ~~development~~our next Phase 2 study.

~~Infectious~~We ~~Disease~~are ~~Pipeline~~developing TNX-1900 (intranasal potentiated oxytocin) for several CNS disorders through investigator-initiated studies. TNX-1900 is in development through investigator-initiated studies at Massachusetts General Hospital (“MGH”) for the treatment of binge eating disorder (“BED”), adolescent obesity, bone health in pediatric autism, and arginine-vasopressin deficiency.

~~Our~~Finally, ~~infectious~~in ~~disease~~December ~~portfolio~~2025, ~~includes~~we in-licensed ~~vaccines~~TNX-4900, ~~based~~formerly onknown ~~our~~as ~~live~~PW507, ~~virus~~from ~~vaccine~~Rutgers orUniversity. ~~recombinant~~TNX-4900 ~~pox~~is ~~vaccine~~a ~~(“RPV”)~~highly selective ~~platform.~~S1R ~~Live~~antagonist ~~virus~~with ~~vaccines~~demonstrated ~~are~~analgesic ~~believed~~activity toin ~~protect~~multiple ~~against~~models ~~poor clinical outcomes~~ of ~~infectious~~neuropathic ~~diseases~~pain. byTNX-4900 ~~eliciting~~is ~~T cell responses~~ in ~~addition~~the topre-IND ~~antibody~~stages of ~~responses~~development.

~~TNX-801, a live minimally replicative vaccine based on synthesized~~Immunology ~~horsepox, is in the pre-IND stage of development to protect against smallpox~~ and ~~mpox.~~Infectious In 2022 the WHO determined that the upsurge of mpox Clade IIb constituted a public health emergency of international concern (PHEIC). Mpox Clade IIB subsequently has become endemic in the U.S. mostly in populations of men who have sex with men. In August 2024, the WHO determined that the upsurge of mpox clade Ib in a growing number of countries in Africa constituted a PHEIC. The WHO reaffirmed the PHEIC status of mpox clade Ib in February of 2025. Mpox cases of the new clade Ib mpox have been detected in the United States and many other countries outside of Africa. Non-human primates vaccinated with TNX-801 were protected from mpox clade Ia in studies reported in the first quarter of 2020 and published in the peer-reviewed journal Vaccines in 2023.Disease

InOur ~~September~~lead ~~2024,~~candidate ~~at the DoD’s MHSRS conference and~~ in ~~October 2024 at~~ the ~~World~~ ~~Vaccine~~infectious ~~Congress~~disease inpipeline ~~Barcelona,~~is ~~Spain, Tonix presented new data on a potential mpox vaccine,~~ TNX-~~801,~~4800. ~~demonstrating tolerability~~Tonix ~~and~~in-licensed noworldwide ~~evidence~~rights ~~of spreading~~ to ~~blood~~TNX-4800 or(formerly ~~tissues,~~known ~~even~~as atmAb ~~high doses~~2217LS), in ~~immunocompromised~~September ~~animals~~2025. ~~After a single-dose vaccination,~~ TNX-~~801 prevented~~4800 ~~clinical~~is ~~disease and lesions, and also decreased shedding in the mouth and lungs of animals after~~ a ~~lethal~~long-acting ~~challenge~~fully ~~with~~human ~~clade~~monoclonal Iaantibody ~~monkeypox.~~that ~~These~~targets ~~findings~~the ~~are~~outer ~~consistent~~surface ~~with~~protein ~~TNX-801~~A ~~inducing~~(OspA) ~~mucosal~~of ~~immunity~~Borrelia ~~and suggest TNX-801 may block forward transmission. In September 2024~~burgdorferi, the ~~Company~~causative ~~also~~agent ~~announced~~of ~~that~~Lyme ~~the~~disease ~~WHO’s~~in ~~preferred target product profile (“TPP”) aligns with the~~humans. ~~characteristics of~~ TNX-~~801.~~4800 ~~Key~~is ~~elements~~being ofdeveloped ~~the~~for ~~WHO~~annual ~~draft~~seasonal ~~TPP~~use ~~include~~and ~~single-dose,~~was ~~durable~~invented ~~protection,~~and ~~administration~~developed ~~without~~by ~~special equipment,~~researchers ~~and stability~~ at ~~ambient~~UMass ~~temperature.~~Chan ~~Other~~Medical ~~potential~~School, ~~beneficial~~which has ~~characteristics~~licensed ~~include~~ the ~~ability~~technology to ~~limit~~Tonix. ~~forward~~There ~~transmission, use~~are incurrently ~~case~~no FDA-~~contact~~approved ~~vaccination~~vaccines ~~strategies~~or ~~and~~prophylactics ~~suitability~~to ~~for~~protect ~~use~~against inLyme ~~immunocompromised individuals~~disease.

TNX-4800 has an engineered extended half-life and targets the outer-surface protein A (OspA) on Lyme-causing Borrelia bacteria. By binding OspA when TNX-4800 containing blood is ingested by the tick, TNX-4800 kills and blocks the maturation of Borrelia burgdorferi in the mid-gut of infected deer ticks. Published work in non-human primates showed that TNX-4800 was 95% effective in preventing infection after 6 days of exposure to ticks infected with Borrelia burgdorferi. TNX-4800 was derived from mAb 2217 by amino acid substitutions in its crystallizable fragment (Fc) domain which served to prolong the serum half-life. A single administration in the Spring is designed to provide onset of immunity within two days and maintain protective antibody titers for the entire tick season, providing pre-exposure prophylaxis against Lyme disease without relying on the recipient’s immune system to generate antibodies. By delivering a well-characterized antibody directly, TNX-4800 has been shown to block transmission of the major Borrelia genospecies from ticks to animals. TNX-4800 also sidesteps the elaborate immunization schedules required for OspA vaccines in development and an FDA-approved vaccine that was withdrawn from the market. Tonix intends to advance TNX-4800 through additional clinical trials with the goal of submitting a Biologics Licensing Application (BLA) to the FDA.

We intend to meet with the FDA in 2026 to explore Phase 2/3 development options for TNX-4800, including a Phase 2 field study and a Phase 2 human challenge study. The proposed field study would test TNX-4800 for prevention of Lyme in volunteers at risk for Lyme in regions of the U.S. where Lyme is endemic. The proposed challenge study – also called a controlled human infection model (“CHIM”) study – would test the ability of TNX-4800 to protect against Borrelia infection by exposing treated or control volunteers to Borrelia-infected ticks that mimic natural infection. Pending clearances from FDA, we plan to initiate the Phase 2 field study in 2027 and the Phase 2 human challenge study in 2028. Production of investigational product under GMP is underway to enable initiation of the field early in 2027, pending FDA clearance. In animals, TNX-4800 provides protection in approximately two days against the bacteria that causes Lyme disease after a single administration. The passive immunity conferred by TNX-4800 is very different from the active immunity conferred by vaccines in development to protect against Lyme disease in that TNX-4800 kills and blocks the metamorphic-like transformation of Borrelia in the tick’s midgut, preventing transmission of the bacteria, whereas vaccines illicit an immune response in the body of a vaccinated person. Prophylaxis with TNX-4800 may also mitigate some of the limitations of vaccine products designed to actively immunize against Lyme, including suboptimal immune responses due to age, immunocompetence, and other reasons.

InWithin ~~October~~immunology, ~~2023~~we are developing TNX-1500, atan ~~the~~Fc-modified ~~World~~humanized mAb, ~~Vaccine~~directed ~~Congress~~against CD40-ligand ~~Europe~~(CD40L, wealso ~~reported~~known ~~that~~as CD154). TNX-1500 was engineered to modulate binding to Fc receptors with the goal of maintaining the activity of first-generation mAbs, yet with reduced risk of thrombotic complications. TNX-~~801~~1500 ~~vaccine~~is ~~was~~being ~~shown~~developed to prevent beorgan ~~greater~~transplant ~~than~~rejection 10as well as to treat autoimmune conditions. Topline results from a Phase 1 single ascending dose escalation study at 3 mg/kg,~~000-fold~~ ~~more~~10 ~~minimally~~mg/kg ~~replicative~~and ~~than~~30 ~~older~~mg/kg ~~vaccinia~~of TNX-~~based~~1500 ~~smallpox vaccines~~ in ~~both~~healthy ~~human~~volunteers ~~primary~~were ~~cell~~reported ~~lines~~in ~~and~~the ~~immunocompromised~~first ~~mice~~quarter of 2025. InPharmacokinetic results ~~October~~showed ~~2024,~~mean athalf-life (t1/2) for the ~~World~~10 ~~Vaccine~~mg/kg ~~Congress~~and 30 mg/kg dose groups of 34-38 ~~Europe~~days, weconsistent ~~highlighted~~with ~~positive~~monthly dosing. ~~preclinical~~In ~~efficacy~~healthy ~~data~~volunteers, of TNX-~~801,~~1500 ~~demonstrating~~was ~~tolerability~~generally well-tolerated with a favorable safety profile. Anti-CD40L has multiple potential indications in ~~immunocompromised~~addition ~~animals~~to solid organ and ~~showed~~bone ~~that~~marrow ~~TNX~~transplantation including autoimmune diseases. In November 2025, we announced an investigator-~~801~~initiated study iswith ~~unable~~MGH, a founding member of Mass General Brigham (“MGB”), to ~~spread~~conduct a Phase 2 clinical trial evaluating TNX-1500 in ~~blood~~kidney ortransplant ~~tissues~~recipients. inThe ~~these~~investigator-initiated ~~animals~~study will be led by Ayman Al Jurdi, ~~even~~M.D., at anMGH ~~approximately~~and ~~100~~is designed to assess the safety, tolerability and activity of Fc-~~fold~~modified ~~higher~~anti-CD40L mAb TNX-1500 in preventing kidney transplant rejection while significantly minimizing the dose ~~than~~of ~~20th~~conventional ~~century~~immunosuppressive ~~vaccinia~~drugs, ~~vaccines~~which inare ~~immune-comprised~~associated with infection, cancer, cardiovascular side effects ~~mice~~and various metabolic derangements. ~~These~~The ~~data~~study ~~were~~is ~~published~~expected into ~~the~~be ~~peer~~initiated mid-~~reviewed~~year ~~journal~~2026 ~~mSphere~~pending inFDA ~~2024~~clearance of the IND.

Our immunology pipeline also includes TNX-~~801~~1700, ~~also~~a ~~serves~~recombinant asTrefoil ~~the~~Factor ~~live~~Family ~~virus~~2 ~~vaccine~~fused ~~platform~~to ~~for~~human ~~other~~serum ~~infectious~~albumin (“hTFF2-HSA”) ~~diseases~~that ~~for~~was ~~which~~licensed ~~subsequent~~from ~~products~~Columbia ~~will~~University bein ~~designed~~2019. byTNX-1700 ~~expressing~~is ~~other~~an ~~viral~~immunotherapy ~~antigens~~being developed to treat gastric and colorectal cancers, in combination with PD-1 blockers, and is at the ~~horsepox~~preclinical ~~vector~~stage of development. ~~The~~Results ~~company’s~~of preclinical testing demonstrated that a ~~Good~~mouse ~~Manufacturing~~version ~~Practice~~of ~~(“GMP”)~~TNX-~~capable~~1700 ~~advanced~~was ~~manufacturing~~able ~~facility~~to evoke an increase in ~~Dartmouth,~~anti-tumor MAimmunity ~~was~~in ~~purpose~~combination with anti-~~built~~PD-1 toin ~~manufacture~~several mouse models ~~TNX~~of gastric cancer by reducing immunosuppressive neutrophils and activating anti-~~801~~tumoral CD8+ T cell responses. ~~The~~TNX-1700 ~~GMP~~as ~~suites~~both ~~are~~monotherapy and ~~currently~~in ~~decommissioned~~combination ~~but~~with ~~are~~anti-PD-1 ~~ready~~was also able to bedramatically ~~reactivated~~reduce metastasis and increase survival in ~~case~~these models. TNX-1700 also exhibits efficacy in various mouse models of acolorectal ~~national~~cancer orin ~~international~~combination ~~emergency~~with anti-PD-1. An INTERACT (INitial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs) meeting was held with the FDA in 2025 and received constructive early guidance on program development.

~~TNX-1800~~Our isinfectious adisease ~~live~~portfolio ~~virus~~includes ~~vaccine~~vaccines based on ~~the~~our ~~RPV~~live ~~platform that expresses the~~virus ~~SARS-CoV-2~~vaccine ~~spike~~or ~~protein~~recombinant ~~from~~pox ~~the~~vaccine ~~ancestral~~(“RPV”) ~~Wuhan~~platform. ~~strain,~~Live ~~which~~virus ~~has~~vaccines ~~shown~~are ~~encouraging~~believed ~~results~~to inprotect ~~non-human~~against ~~primates.~~poor Inclinical ~~June 2024, the~~outcomes ~~Company~~of ~~announced~~infectious ~~preclinical~~diseases ~~data,~~by ~~demonstrating~~eliciting ~~immunity~~T-cell ~~and~~responses ~~tolerability,~~in ~~during~~addition anto ~~oral~~antibody ~~keynote talk at the Vaccine Congress 2024~~responses. ~~Like~~ TNX-801, ~~TNX-1800 is~~ a live minimally replicative vaccine based on synthesized horsepox, ~~that~~ is ~~believed~~in tothe ~~provide immune protection with better tolerability than modern vaccinia viruses. TNX~~pre-~~1800~~IND ~~was~~stage ~~selected by the NIH’s Project NextGen for inclusion in clinical trials as part~~ of adevelopment ~~select group of next generation COVID-19 vaccine candidates with the intent~~ to ~~identify~~protect ~~promising~~against ~~vaccine~~smallpox ~~platforms. If Tonix is able to provide TNX-1800 to NIH, they would conduct a Phase 1 trial~~ and ~~cover the full cost~~mpox. ~~However,~~Preclinical ~~Tonix~~data/studies ~~has not prioritized the~~demonstrate ~~production~~that of TNX-~~1800~~801, soregardless itof isroute ~~uncertain~~of ~~whether~~administration ~~or how quickly this project will progress~~(i. ~~The COVID-19 vaccines approved for use in the U~~e.S. ~~have~~intradermal, ~~provided~~subcutaneous ~~significant~~or ~~health benefits to the vaccinated population; however~~intramuscular), ~~they~~provided ~~have~~100% ~~shown limitations in the durability of~~ protection ~~conferred, and in their ability to block forward transmission. Live virus vaccines that protect~~ against ~~other viral diseases~~ byvaccinia ~~eliciting~~virus ~~T cell responses have shown durability of protection that lasts years to decades,~~ and ~~some~~monkeypox ~~live~~ virus ~~vaccines have significantly inhibited forward transmission. With respect to TNX-1800 vaccination, we reported positive efficacy data from animal~~ challenge ~~studies using live SARS-CoV-2~~ in ~~the~~terms ~~first quarter~~ of ~~2021.~~both ~~These~~mortality ~~data~~and ~~were~~clinical ~~published~~disease in(lesions) ~~the peer-reviewed journal Vaccines~~ in ~~2023.~~a ~~In this~~highly ~~study,~~sensitive ~~TNX-1800 vaccinated, SARS-CoV-2 challenged animals had undetectable SARS-CoV-2 in the upper airways, which we believe relates~~rabbitpox ~~to potential inhibition of forward transmission of this respiratory pathogen~~model.

~~Tonix is~~TNX-801 ~~developing~~also ~~potential~~serves ~~broad-spectrum~~as ~~antiviral~~the ~~drugs~~live invirus ~~three~~vaccine ~~programs:~~platform ~~CD45-targeted~~for ~~therapeutics~~other ~~(TNX-4200)~~infectious diseases, ~~cathepsin~~for ~~inhibitors (TNX-3900)~~which ~~and~~subsequent ~~viral~~products ~~glycan-targeted~~will ~~engineered~~be ~~biologics~~designed ~~(TNX-4000).~~by ~~The~~expressing ~~DoD~~other ~~announced~~viral antigens in ~~December~~the ~~2022~~horsepox avector. ~~plan~~Our toGMP-capable ~~move beyond~~advanced amanufacturing ~~‘one~~facility ~~bug~~in Dartmouth, ~~one~~Massachusetts ~~drug’~~was ~~approach~~purpose-built ~~and~~to ~~are~~manufacture ~~seeking broad~~TNX-~~spectrum~~801. ~~drugs~~The ~~since~~GMP itsuites are currently decommissioned and may be ~~hard~~reactivated toon ~~predict~~the ~~which~~earlier of 2027 or ~~how~~in ~~many viruses~~the ~~may~~case beof ~~deployed~~a onnational ~~the~~or ~~battlefield~~international emergency.

InWe ~~July~~are ~~2024~~developing ~~Tonix was awarded~~ a ~~contract with a~~ potential ~~for up to $34 million over five years by the Defense Threat Reduction Agency (DTRA), an agency within the DoD. The objective of the contract is to develop small molecule~~ broad-spectrum antiviral ~~agents~~CD45-targeted ~~for the prevention or treatment of infections to improve the medical readiness of military~~therapeutic ~~personnel in biological threat environments. Tonix’s program will focus on optimization and development of its~~ (TNX-4200). ~~program, to~~The ~~develop~~DoD anannounced ~~orally~~in ~~available~~December ~~CD45~~2022 ~~antagonist with broad-spectrum efficacy against~~ a ~~range~~plan ~~of viral families through preclinical evaluation. The program is expected~~ to ~~establish~~move ~~physicochemical~~beyond ~~properties, pharmacokinetics, and safety attributes to support an IND submission and to fund~~ a ~~first-in-human~~“one ~~Phase 1 clinical study. Tonix plans to leverage previous research on phosphatase inhibitors~~bug, ~~specifically compounds~~one ~~that~~drug” ~~target~~approach ~~CD45, to optimize lead compounds for therapeutic intervention of biothreat agents~~ and ~~provide~~is ~~the government with~~seeking ~~a complete and cost-effective solution for a~~ broad-spectrum ~~medical~~drugs ~~countermeasure.~~as ~~Tonix’s~~it ~~premise~~may isbe ~~that~~hard ~~partial~~to ~~inhibition~~predict ~~of CD45~~which ~~will~~or ~~provide~~how ~~optimal~~many ~~antiviral~~viruses ~~protection~~may ~~while~~be ~~requiring~~deployed ~~lower~~on ~~plasma~~the ~~drug concentrations, a lower dose, and a better safety profile~~battlefield.

~~Tonix~~In July ~~will~~2024, ~~utilize~~we ~~its~~were ~~state-~~awarded a contract with a potential for up to $34 million over five years by DTRA. The objective of the contract is to develop small molecule broad-spectrum antiviral agents for the prevention or treatment of infections to improve the medical readiness of military personnel in biological threat environments. The program focuses on optimization and development of TNX-~~art~~4200 ~~research~~to ~~laboratory~~develop ~~capabilities,~~an orally available CD45 antagonist ~~including~~with broad-spectrum efficacy against a ~~Biosafety~~range ~~Level~~of 3viral ~~(BSL-3)~~families ~~lab~~through preclinical evaluation. The program is expected to establish physicochemical properties, pharmacokinetics, and safety attributes to support an ~~Animal~~IND ~~Biosafety~~submission ~~Level~~and 3to ~~(ABSL~~fund a first-3)in-human Phase ~~facility~~1 atclinical ~~the~~study. ~~RDC~~Tonix plans to leverage previous research on phosphatase inhibitors, asspecifically ~~well~~compounds asthat ~~experienced~~target CD45, ~~personnel~~to optimize lead compounds for therapeutic intervention of biothreat agents and provide the government with a complete and incost-~~house~~effective solution for a broad-spectrum medical countermeasure. We believe that partial inhibition of CD45 will provide optimal antiviral protection while requiring lower plasma drug concentrations, a lower dose, and a better safety profile.

We will utilize our state-of-the-art research laboratory capabilities, including a Biosafety Level 3 (BSL-3) lab and Animal Biosafety Level 3 (ABSL-3) facility, in Frederick, Maryland (“RDC”), as well as experienced in-house personnel, to develop vaccines and antiviral therapies for mpox, smallpox and other infectious diseases. We intend to collaborate with academic partners to test the efficacy of CD45 inhibitor compounds against multiple viral select agents using BSL-4 facilities.

Rare Disease Pipeline

Our rare disease portfolio consists of TNX-2900 (intranasal potentiated oxytocin) for Prader-Willi syndrome (“PWS”), a rare genetic disorder ~~characterized~~and bythe ~~complex~~leading ~~symptoms~~cause of life-threatening childhood obesity, affecting about 1 in 10,000 to 1 in 30,000 births. Infants often present with poor muscle tone and feeding difficulties, while children and adolescents develop hyperphagia, behavioral challenges, and severe obesity and metabolic disease. Current interventions are difficult to sustain and often inadequate. The formulation technology for TNX-2900 was acquired from Trigemina, Inc. and licensed from Stanford University in 2020. The potentiated formulation includes magnesium, which has been shown in animal studies to potentiate binding of oxytocin to the oxytocin receptor. The therapeutic technology was licensed from Inserm, the French National Institute of Health and Medical Research. TNX-2900 was granted Orphan-Drug Designation by the FDA in the second half of 2023, and the IND was cleared by the FDA in the fourth quarter of 2023, and received Rare Pediatric Disease Designation on in March ~~21,~~ 2024~~. PWS~~, anwhich ~~orphan~~would ~~condition,~~make isus aeligible ~~rare~~for ~~genetic disorder of failure to thrive in infancy, associated with uncontrolled appetite beginning in childhood with complications of obesity and diabetes. We have sponsored~~ a ~~research~~transferable ~~program at Inserm to study oxytocin~~Priority onReview ~~suckling~~Voucher ~~behavior~~upon ~~in mice that have been engineered to express one of the PWS gene mutations~~approval.

~~Marketed~~We ~~Medicines~~plan to progress our TNX-2900 program for the treatment of PWS into a Phase 2, randomized, double-blind, placebo-controlled, parallel-design study to evaluate the safety, tolerability, and efficacy of TNX-2900 in male and female participants with PWS, ages 8 to 17.5 years. Eligible participants will be randomized to receive 12-weeks of treatment with TNX-2900 at one of three dose levels, or placebo, in a 1:1:1:1 ratio. The primary efficacy endpoint will be the change from baseline in the validated Hyperphagia Questionnaire for Clinical Trials (HQ-CT), a widely used measure of hyperphagia severity in PWS. Secondary objectives will include assessments of behavior, caregiver burden, and quality of life measures, as well as safety and tolerability outcomes. We intend to initiate enrollment in this study in the first quarter of 2027.

Our commercial portfolio consists of two FDA-approved prescription products for the treatment of migraine: Zembrace SymTouch (sumatriptan injection) 3 mg and Tosymra (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are both indicated for the treatment of acute migraine with or without aura in adults. Zembrace SymTouch is the only branded sumatriptan autoinjector professionally promoted in the United States and is designed for ease of use and favorable tolerability with a low 3 mg dose. Tosymra is a novel intranasal sumatriptan product formulated with a permeation enhancer that provides rapid and efficient absorption of sumatriptan. Tosymra was approved on the basis of bioequivalence to subcutaneous (s.c.) sumatriptan. Tonix Medicines is the only manufacturer with both a branded injectable and nasal spray indicated for the acute treatment of migraine with or without aura in adults.

In September 2024, Tonix announced that the United States Patent and Trademark Office (USPTO) issued U.S. Patent No. 12,097,183 to the Company, claiming use of a pre-filled autoinjector comprising a composition of Zembrace® SymTouch® for treating migraines via subcutaneous administration. This patent, excluding possible patent term extensions, is expected to fortify protection and market exclusivity into 2036. Additionally, Tonix announced that the USPTO issued U.S. Patent No. 12,090,139 to the Company, claiming a pharmaceutical composition, a method of treating migraine via intranasal administration, and an intranasal delivery system for Tosymra®. This patent is expected to fortify protection and market exclusivity into 2030.

In June 2024, the Company presented data at the 66th Annual Scientific Meeting of the American Headache Society (AHS) comparing real-world data with real-world usage of non-oral migraine products with the most recent AHS consensus statement. This data stressed the need for customizing treatment of migraine headaches to the needs of patients. Thus far, real world data show that conformity with the guidelines and the consensus statement have yet to be achieved but has the potential to be increased. The data show the use of non-oral drugs for treating an acute migraine attack was only 7% in 2012 and has decreased to below 4% in 2023, when the potential need for such drugs is anticipated to be a more substantial percentage of migraineurs based on epidemiological data. In 2024, Tonix Medicines launched a national educational campaign focusing on the link between migraine, gastroparesis, and the need for non-oral acute migraine therapies.

Facilities

Relating to our development programs, we own and operate the RDC in Frederick, Maryland consisting of one building totaling approximately 48,000 square feet. The RDC conducts research on CNS, immunology, and infectious disease candidates. The RDC facility is mostly biosafety level 2 (BSL-2), with some components designated BSL-3. We also own an Advanced Development Center (“ADC”) located in the New Bedford business park in Dartmouth, Massachusetts. This approximately 45,000 square foot BSL-2 facility is intended to accelerate development, clinical and commercial scale manufacturing of live-virus vaccines and biologics to support clinical trials. This facility was decommissioned in 2024, ~~but~~and ~~Tonix~~may ~~has~~be reactivated on the ~~ability~~earlier toof ~~reactivate~~2027 itor ~~should~~in wethe case ~~choose~~of toa donational soor international emergency.

We are led by a management team with significant industry experience in commercialization and drug development. We complement our management team with a network of scientific, clinical, and regulatory advisors that includes recognized experts in their respective fields.

Our Strategy

Our strategy is to use our integrated development and marketing capabilities to advance innovative programs across multiple therapeutic areas through the drug development process, with the ultimate objectives of FDA approval and commercialization. The principal components of our strategy are to:

● Pursue CNS, rare disease, immunology, and infectious disease indications with high unmet medical need and significant commercial potential. We are pursuing multiple indications that are underserved with limited, effective treatment options. Our latest stage product candidate is TNX-102 SL for the management of FM, a condition which affects between 6-12 million adults in the U.S. Fewer than half of those treated for FM receive relief from the three FDA-approved drugs. Our broader development strategy is to leverage the patented formulation and proven mechanism of action to explore the clinical potential of TNX-102 SL in multiple other, psychiatric, and addiction conditions, including ASR, ASD, AAD and AUD, all of which are underserved by currently approved medications or have no approved treatment. Within CNS, Tonix is also developing TNX-1300 to treat cocaine intoxication and TNX-1900 to treat binge eating disorder, adolescent obesity, social anxiety disorder and improvement in bone health in autism. Cocaine intoxication is one of the leading causes of overdose deaths and for which there is no currently approved drug. With TNX-1500, we are pursuing a treatment to prevent organ transplant rejection as well as autoimmune conditions. TNX-1500 is a third generation humanized mAb targeting CD40L that has the potential to deliver efficacy without compromising safety, based on modulated binding to Fc receptors. At this time, no mAb against CD40L has been licensed anywhere in the world. Within infectious diseases, we are currently focusing on the development of TNX-801 to prevent smallpox and mpox. While there are FDA-approved vaccines to prevent smallpox and mpox, we believe TNX-801 has potential to provide durable protection. While there are FDA-approved COVID-19 vaccines which use mRNA technology, or other technologies, we believe that there are limitations to these vaccines relating to durability of protection and their relative inability to block forward transmission.

●

Drive the successful commercialization of TONMYA for the treatment of fibromyalgia in the United States. TONMYA was approved by the FDA in August 2025 for the treatment of fibromyalgia in adults. We launched TONMYA in the United States in November 2025 and an important objective is to establish TONMYA as the standard of care for fibromyalgia. We have approximately 90 U.S. sales representatives who are focused on promoting TONMYA to physicians and other healthcare prescribers who treat fibromyalgia, including rheumatologists, primary care physicians, pain specialists, neurologists and psychiatrists.

●

Maximize the commercial potential of our product candidates. We plan to commercialize our product candidates, either on our own or through collaboration with partners. Alternatively, we could enter into partnership agreements with drug companies that already have significant marketing capabilities in the same, or similar, therapeutic areas.

● ~~Maximize~~Pursue ~~the~~additional indications and commercial ~~potential~~opportunities offor our ~~lead~~ product candidates. We plan to ~~commercialize~~maximize ~~each~~the value of ~~our~~certain ~~lead product candidates, including our latest stage candidate, TNX-102 SL, either on our own or through collaboration with partners. We believe the acquisition~~ of our ~~two FDA-approved, marketed~~ products ~~for~~and ~~the~~product ~~treatment~~candidates ofby ~~acute~~pursuing ~~migraine~~other ~~(Zembrace~~indications ~~SymTouch~~ and ~~Tosymra)~~commercial ~~positions~~opportunities ~~Tonix~~for tosuch ~~build~~candidates. ~~out~~For ~~commercial~~example, ~~capability~~we toare ~~market~~exploring the ~~migraine~~development ~~products~~ and tocommercialization ~~launch~~of TNX-102 SL for ~~fibromyalgia.~~MDD, AnASD/ASR ~~alternative~~and ~~strategy~~other ~~would~~important beindications. toFor ~~enter~~TNX-1900, ~~into~~we ~~partnership~~are ~~agreements~~exploring ~~with~~the ~~drug~~development ~~companies~~for ~~that~~the ~~already~~treatment ~~have~~of ~~significant~~binge ~~marketing~~eating ~~capabilities in the same~~disorder, oradolescent ~~similar~~obesity, ~~therapeutic~~bone ~~areas.~~health Ifin wepediatric ~~determine~~autism, ~~that~~and ~~such~~arginine-vasopressin adeficiency. ~~strategy~~Finally, ~~would~~our belive ~~more~~virus ~~favorable~~platform ~~than~~using ~~developing~~ our ~~own~~RPV ~~sales~~technology ~~capabilities,~~may webe ~~will~~developed ~~seek~~as tovaccines ~~enter into collaborations with pharmaceutical or biotechnology companies~~ for ~~commercialization.~~future Inpandemics, ~~preparation~~infectious ~~for~~diseases ~~the launch of TNX-102 SL~~generally, wein ~~have~~addition ~~added~~ to ~~our~~smallpox ~~team of professionals to market~~ and ~~distribute~~mpox, ~~our products. Our commercial team is engaged in marketing~~ and ~~distributing~~for ~~our~~oncology ~~products and is also engaged in planning the launch of TNX-102 SL contingent on FDA approval~~applications.

● Pursue a broad intellectual property strategy to protect our product candidates. We are pursuing a broad patent strategy for our product candidates, and we endeavor to generate new patent applications as supported by our innovations and conceptions as well as to advance their prosecution. In the case of TNX-102 SL, we own patents and patent applications protecting its composition-of-matter, certain methods of its use, its formulation, and its pharmacokinetic properties. In the case of TNX-801 and TNX-1800, we own patent applications protecting their composition-of-matter and certain methods of use. We also own patents through in-licensing transactions for TNX-1300, TNX-1900, TNX-2900, and TNX-1700. We have filed patent applications for TNX-1500. We plan to opportunistically apply for new patents to protect our product candidates. 8

9● Pursue CNS, rare disease, immunology, and infectious disease indications with high unmet medical need and significant commercial potential. We are pursuing multiple indications that are underserved with limited, effective treatment options. Our broader development strategy is to leverage the patented formulation and proven mechanism of action to explore the clinical potential of TNX-102 SL in multiple other, psychiatric, and addiction conditions, including MDD, ASR and ASD, all of which are underserved by currently approved medications or have no approved treatment. One of our latest stage product candidates is TNX-102 SL for the treatment of MDD, a condition which affects more than 21 million adults in the U.S. While several antidepressant medications are available, many individuals do not achieve adequate relief or discontinue treatment due to side effects like weight gain, sleep disruption, and sexual dysfunction. Cocaine intoxication is one of the leading causes of overdose deaths and for which there is no currently approved therapy, however, those studies are currently on hold. Within CNS, Tonix is also developing TNX-1300 to treat cocaine intoxication and TNX-1900 to treat binge eating disorder, adolescent obesity, bone health in pediatric autism, and arginine-vasopressin deficiency. With TNX-4800, we are pursuing a prevention for Lyme disease, which has the potential to affect millions of people and for which there is no current prophylaxis. With TNX-1500, we are pursuing a treatment to prevent organ transplant rejection as well as autoimmune conditions. TNX-1500 is a third generation humanized mAb targeting CD40L that has the potential to deliver efficacy without compromising safety, based on modulated binding to Fc receptors. At this time, no mAb against CD40L has been licensed anywhere in the world. Within infectious diseases, we are also focusing on the development of TNX-801 to prevent smallpox and mpox. While there are FDA-approved vaccines to prevent smallpox and mpox, we believe TNX-801 has potential to provide durable protection.

● Pursue ~~additional~~a ~~indications~~broad ~~and~~intellectual ~~commercial~~property ~~opportunities~~strategy ~~for~~to protect our product candidates. We ~~plan~~are topursuing ~~maximize~~a ~~the~~broad ~~value~~patent ofstrategy for our ~~other~~ product candidates, ~~by pursuing other indications~~ and ~~commercial~~we ~~opportunities~~endeavor ~~for~~to ~~such~~generate ~~candidates.~~new ~~For~~patent ~~example,~~applications weas ~~own~~supported ~~rights~~by ~~related~~our toinnovations ~~the development~~ and ~~commercialization~~conceptions ofas ~~TNX-102~~well SLas ~~for~~to ~~generalized~~advance ~~anxiety~~their ~~disorder,~~prosecution. ~~depression,~~In ~~and~~the ~~fatigue~~case ~~related~~of ~~to disordered sleep. For TNX-1900~~TONMYA, we own ~~the~~patents ~~rights~~and topatent ~~develop~~applications ~~this~~protecting ~~for~~its ~~craniofacial pain~~composition-of-matter, ~~and~~certain ~~insulin~~methods ~~resistance.~~of ~~Finally~~its use, ~~our~~its ~~live~~formulation, ~~virus~~and ~~platform~~its ~~using~~pharmacokinetic ~~our~~properties. ~~RPV~~We ~~technology~~plan ~~may~~to beopportunistically ~~developed~~apply ~~as vaccines~~ for ~~future~~new ~~pandemics,~~patents ~~infectious diseases generally, in addition~~ to ~~smallpox~~protect ~~and~~our ~~mpox,~~product ~~and for oncology applications~~candidates.

Disease and Market Overview

Our product candidates address disorders that are not well served by currently available therapies or have no approved treatment which represent large potential commercial market opportunities. Background information on the disorders and related commercial markets that may be addressed by our product candidates in or nearing the clinical stage of development is set forth below.

Central Nervous System

Fibromyalgia (FM)

Fibromyalgia is a common chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system, called central sensitization. Brain imaging studies have localized the functional disorder to the brain’s insular and anterior cingulate cortex. Fibromyalgia afflicts more than 10 million adults in the U.S., the majority of whom are women. Symptoms of fibromyalgia include chronic widespread pain, non-restorative sleep, fatigue, and brain fog (or cognitive dysfunction). Other associated symptoms include mood disturbances, including depression, anxiety, headaches, and abdominal pain or cramps. Individuals suffering from fibromyalgia often struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products. Fibromyalgia is now recognized as the prototypic nociplastic syndrome. Nociplastic pain is the third primary type of pain in addition to nociceptive pain and neuropathic pain. Many patients present with pain syndromes that are combinations of the three primary types of pain. Nociplastic syndromes can involve components of both central and peripheral sensitization. Fibromyalgia can occur without any identifiable precipitating event. However, many fibromyalgia cases follow one or more precipitating event(s) including: chronic nociceptive or neuropathic pain states; recovery from an infectious illness; a cancer diagnosis or cancer treatment; a metabolic or endocrine stress; or a traumatic event. In the ~~cases~~case of recovery from an infectious illness, fibromyalgia is considered an Infection-Associated Chronic Condition. In addition to fibromyalgia cases associated with other conditions or stressors, the U.S. National Academies of Sciences, Engineering, and Medicine, has concluded that fibromyalgia is a diagnosable condition that occurs after recovery from COVID~~-19~~ in the context of Long COVID. Fibromyalgia is also recognized as a Chronic Overlapping Pain Condition, due to shared symptoms with chronic fatigue syndrome/myalgic encephalomyelitis, irritable bowel syndrome, endometriosis, low back pain, post-concussive syndrome (also known as mild traumatic brain injury), chronic Lyme disease, chronic diabetic neuropathy and chronic post-herpetic neuralgia.

We believe that diagnosing fibromyalgia in Long COVID patients will increase the potential market for TNX-102 SL as compared to market estimates from before the COVID-19 pandemic. Tonix has previously presented its analysis of real-world evidence from the TriNetX claims database suggesting that over 40% of Long COVID patients present with a constellation of symptoms that overlap with fibromyalgia.

~~According to reports by Frost~~Based ~~and~~on ~~Sullivan~~market ~~and~~research ~~Eversana~~which ~~that~~ we commissioned, despite the availability of approved medications, the majority of patients fail therapy due to either insufficient efficacy, poor tolerability, or both. Prescription pain and sleep medications, including opioids, are frequently prescribed off-label for symptomatic relief, despite the lack of evidence that such medications provide a meaningful or durable therapeutic benefit, and many of these medications carry significant safety risks and risk of dependence. For example, based on U.S. claims data, approximately 50% of patients diagnosed with FM are prescribed opioids within 18 months of diagnosis, despite the lack of evidence for their effectiveness and the risk of addiction and toxicity, including overdose.

10Major Depressive Disorder

MDD is a prevalent and serious psychiatric illness that affects adults of all ages, races, and backgrounds. It is characterized by persistent feelings of sadness or loss of interest, along with symptoms such as sleep and appetite disturbances, fatigue, difficulty concentrating, and thoughts of worthlessness or suicide. These symptoms must last at least two weeks and significantly impair daily functioning. In the United States, more than 21 million adults experience a major depressive episode each year. While several antidepressant medications are available, many individuals do not achieve adequate relief or discontinue treatment due to side effects like weight gain, sleep disruption, and sexual dysfunction. MDD is associated with increased risk of suicide and substantial impairment in quality of life, underscoring the urgent need for new, first-line therapies that are both effective and well-tolerated.

Acute Stress Disorder and Acute Stress Reaction

ASD is a mental health condition that can occur within the first month of experiencing a traumatic event. The symptoms are similar to those of PTSD and can affect both civilian and military populations. ASR is a transient, often severe, emotional and physical response occurring minutes to days after a traumatic event, such as assault, disaster, or accident. Symptoms include anxiety, flashbacks, numbness, and insomnia, typically resolving within a few days or up to one month. According to the National Center for PTSD, in the U.S. about 60% of men and 50% of women experience at least one trauma in their lives. In the U.S. alone, one-third of emergency department visits (40-50 million patients per year) involve evaluation after trauma exposures, and in a 2014 study involving U.S. veterans, 87% reported exposure to at least one potentially traumatic event during their service. No medications are currently available at or near the point of care to treat patients suffering from acute traumatic events and to support long-term health.

Cocaine Intoxication

Cocaine is an illegal recreational drug taken for its pleasurable effects and associated euphoria. Pharmacologically, cocaine blocks the reuptake of the neurotransmitter dopamine from central nervous system synapses, resulting in the accumulation of dopamine within the synapse and an amplification of dopamine signaling that is related to its role in creating positive feeling. With the continued use of cocaine, however, intense cocaine cravings occur resulting in a high potential for abuse and addiction, or dependence, as well as the risk of cocaine intoxication. Cocaine intoxication refers to the deleterious effects on other parts of the body, especially those involving the cardiovascular system. Common symptoms of cocaine intoxication include tachyarrhythmias and elevated blood pressure, either of which can be life-threatening. As a result, individuals with known or suspected cocaine intoxication are sent immediately to the emergency department, preferably by ambulance in case cardiac arrest occurs during transit. There are approximately 505,000 emergency room visits for cocaine abuse each year in the U.S., of which 61,000 require detoxification services. According to the National Institute on Drug Abuse, cocaine-involved deaths rose nearly 54% from 2019 to 2021, resulting in over 24,486 deaths total.

Acute Stress Disorder (ASD)

ASD is a mental health condition that can occur within the first month of experiencing a traumatic event. The symptoms are similar to those of PTSD and can affect both civilian and military populations. According to the National Center for PTSD, in the U.S. about 60% of men and 50% of women experience at least one trauma in their lives. In the U.S. alone, one-third of emergency department visits (40-50 million patients per year) involve evaluation after trauma exposures, and in a 2014 study involving U.S. veterans, 87% reported exposure to at least one potentially traumatic event during their service. No medications are currently available at or near the point of care to treat patients suffering from acute traumatic events and to support long-term health.

Immunology

Organ Transplant Rejection

Organ transplant rejection occurs when the immune system of the organ recipient attacks the new organ as if it was an infection or tumor. Often transplantation is the last resort for most end-stage organ failure patients, affecting either kidneys, liver, heart, lungs, and/or pancreas. Genetic disparity between organ donor and recipient is often at the root of the rejection. Mismatched or not closely matched organs ~~triggers~~trigger an immune reaction that leads to rejection. Overcoming this difficulty is paramount to a patient’s survival as organ donations are in limited supply.

~~Gastric and Colorectal cancers~~ 10

Gastric and Colorectal Cancers

Gastric or stomach cancer is a disease in which malignant cancer cells line the inner lumen of the stomach. Development of this form of cancer is often influenced by age, diet and other stomach diseases. This type of cancer begins to form in the mucosa, the surface of the lumen that is in direct contact with the contents of the stomach, and spreads through the outer layers of the stomach as the tumor grows.

Currently, per the National Cancer Institute, the 5-year relative survival for stomach cancer is 36.4%. According to 2018-2021 data, approximately 0.8 percent of men and women will be diagnosed with stomach cancer during their lifetime. In 2021, there were an estimated 130,263 people living with stomach cancer in the U.S. As of 2024, there were approximately 26,890 new cases with 10,880 deaths.

Colorectal cancer includes cancers in the colon and the rectum, organs that are crucial to absorption of water by the body and the elimination of food-waste. Most colorectal cancers start as a growth or polyp on the inner lining of the colon or rectum. Some types of polyps can change into cancer over time (usually many years), but not all polyps become cancer. Adenomatous polyps are the ones that turn malignant with time. Similar to gastric cancer, malignancy begins in the mucosal layer and spreads outwards.

The 5-year relative survival rate with colorectal cancer is 65.0%, per the National Cancer Institute. Based on 2018-2021 data, approximately 4.0 percent of men and women will be diagnosed with colorectal cancer during their lifetime. In 2021, there were an estimated 1,392,445 people living with colorectal cancer in the United States. As of 2024, there were approximately 152,810 new cases with 53,010 deaths. It is the 3^rd leading cause of cancer death in women, and 2^nd in men.

Infectious Diseases

Lyme Disease

Lyme disease is caused by the bacterium Borrelia burgdorferi. Lyme disease remains the most common vector-borne infection in the United States and its incidence is climbing each year. It occurs most commonly in the Northeast, mid-Atlantic, and upper-Midwest regions. Lyme disease bacteria are transmitted through the bite of infected Ixodes ticks. Typical symptoms include fever, headache, fatigue, and a characteristic skin rash called erythema migrans. If left untreated, infection can spread to joints, the heart, and the nervous system. Laboratory testing is helpful if used correctly and performed with FDA-cleared tests.

Smallpox and Mpox

Smallpox is an acute contagious disease caused by the variola virus, or VARV, which is a member of the orthopoxvirus family. Smallpox was declared eradicated in 1980 following a global immunization campaign. Smallpox is transmitted from person to person by infective droplets during close contact with infected symptomatic people. Mpox is an acute contagious disease caused by the monkeypox virus or MPXV, which is also a member of the orthopoxvirus family. Mpox symptoms are similar to those of smallpox, although less severe. Mpox is emerging as an important zoonotic infection in humans in Central and West Africa. Until 2022, only a few cases of mpox had been reported outside of Africa in patients who had been infected while in Africa. Starting in May of 2022, mpox clade II cases spread rapidly in the U.S. and other countries. The Clade II mpox affects mostly men who have sex with men in the U.S., where it has become endemic. In August 2024, the World Health Organization (“WHO”) declared mpox Clade Ib to be a public health emergency of international concern (“PHEIC”) due to an outbreak in the Democratic Republic of the ~~Congo~~ Congo that spread globally, including to the United States. Clade Ib affects children as well as adults. ~~The~~Although ~~WHO~~PHEIC ~~reaffirmed~~designation has ~~the~~been ~~PHEIC~~lifted ~~status~~by ofWHO, mpox ~~clade~~continues Ibto spread in ~~February~~Africa and mutations of ~~2025~~the virus are considered by public health experts to be an ongoing threat to be monitored for new epidemic spread.

Smallpox was eradicated by a World Health Organization program that vaccinated individuals with live replicating vaccinia vaccines wherever smallpox appeared. In the 1970s, vaccination of civilians to protect against smallpox was discontinued in the U.S.; however, smallpox remains a material threat to national security and a proportion of military personnel, including members of the Global Response Force continue to be vaccinated. Vaccines for smallpox and mpox are stockpiled by the U.S. government in the strategic national stockpile and for potential widespread immunization in the event of malicious reintroduction of VARV. The U.S. National Academy of Sciences has recently issued a consensus report raising concerns about the state of new mpox vaccines in development.

12 11

COVID-19

SARS-CoV-2 is a contagious virus causing the disease COVID-19 that became a global pandemic in 2019 and has resulted in more than three million deaths. While the infection and mortality rates have slowed in regions of the world with high vaccination rates, the struggle with the pathogen is ongoing and evolving since SARS-CoV-2 is mutating into new variants. COVID-19 is characterized by fever, sore throat, acute shortness of breath, cough, and oxygen desaturation in the blood. New variants continue to sweep across the world in successive waves. With new variants of the virus emerging, therapeutic research is addressing the challenge of keeping up with this rapidly mutating virus. The early vaccines have been effective in limiting the severity of disease in vaccinated individuals. Vaccines that elicit strong T cell responses are believed to have the potential to provide long-term or durable protection.

Rare Disease

Prader-Willi Syndrome

PWS is recognized as the most common genetic cause of life-threatening childhood obesity and affects males and females with equal frequency and all races and ethnicities. PWS results from the absence of expression of a group of genes, specifically related to the MAGE (melanoma antigen) gene family on the Prader–Willi critical region (15q11–q13) on the paternally acquired chromosome. The hallmarks of PWS are lack of suckling in ~~infants~~newborns and, in children and ~~adults~~adolescents, severe hyperphagia, an– an overriding physiological drive to eat, leading to severe obesity and other complications associated with significant mortality. A systematic review of the morbidity and mortality. ~~PWS~~as isa anconsequence ~~orphan~~of ~~disease~~hyperphagia in PWS found that ~~occurs~~the inaverage ~~approximately~~age ~~one~~of death in ~~15,000~~PWS was ~~births~~22.1 ~~There~~years. Given the serious or life-threatening manifestations of these conditions, there is ~~currently~~a nocritical ~~approved treatment~~need for ~~obesity~~effective treatments to decrease morbidity and ~~hyperphagia~~mortality, improve quality of life, and increase life expectancy in ~~adults~~people with PWS. Oxytocin has potent effects in correcting behavioral characteristics of the MAGEL2 knock-out mouse model for PWS and ~~older~~autism. ~~children~~Six ~~associated~~clinical trials have investigated intranasal oxytocin as a treatment in pediatric patients with PWS. Four clinical studies showed evidence for improvement in PWS-related behaviors/symptoms. Three of these clinical studies reported evidence for improvement in hyperphagia and one showed an improvement in sucking in infants.

Tonix’s Marketed ~~Migraine~~ Products

TONMYA – Treatment of Fibromyalgia

In August 2025, we received approval from the FDA for TONMYA (cyclobenzaprine HCl sublingual tablets) for the treatment of fibromyalgia. TONMYA in adults, Tonix’s first internally developed product, was commercially launched by the Company in the United States on November 17, 2025. TONMYA is the first new treatment for fibromyalgia in more than 15 years and is a centrally acting, differentiated non-opioid analgesic designed for bedtime administration and long-term use, addressing core symptoms of fibromyalgia including pain, disturbed sleep and fatigue. The approval and launch of TONMYA marked a major milestone in our evolution as an organization with growing revenues and an expanding customer footprint. We hold worldwide commercialization rights to TONMYA.

Zembrace SymTouch and Tosymra – Acute Migraine in Adults

In June 2023, we acquired two FDA-approved, marketed products from Upsher-Smith: Zembrace SymTouch (sumatriptan injection) 3 mg and Tosymra (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are both indicated for the treatment of acute migraine with or without aura in adults.

Zembrace SymTouch is the only actively promoted brand of sumatriptan autoinjector in the United States. It has a unique low dose and has demonstrated onset of migraine pain relief in as few as 10 minutes (17% of patients vs. 5% for placebo). Zembrace SymTouch also demonstrated migraine pain freedom for 46% of patients (vs 27% for placebo) at 2 hours in a single-attack, double-blind study (N=230). Zembrace SymTouch currently has patent protection to 2036. Tosymra employs Intravail® permeation enhancer technology and is pharmacokinetically equivalent to 4 mg subcutaneous sumatriptan. Tosymra delivers migraine pain relief in as little as 10 minutes with just one spray for some patients (13% vs. 5% for placebo). Tosymra® currently has patent protection to 2031.

13Together, these products form the foundation of our commercial platform, including sales, marketing, market access, distribution, and patient support capabilities.

~~Lead~~ Product Candidates in Development

We believe that our product candidates offer innovative therapeutic approaches and may provide significant advantages relative to available therapies. We have worldwide commercialization rights to all of our product candidates listed below. The following table summarizes our later stage product candidates that are in or nearing the clinic:

Product Candidate	Indication	~~Stage of Development~~	Stage of Development
TNX-102 SL	~~Fibromyalgia~~Major Depressive Disorder	~~NDA submitted and accepted by FDA for review; PDUFA goal date of August 15, 2025~~	Phase 2 expected to commence mid-2026
TNX-102 SL	Acute Stress Reaction/Acute Stress Disorder	~~Phase 2 ready* – investigator-initiated IND~~	Phase 2 enrolling*
TNX-1300	Cocaine Intoxication	Mid-Phase 2
TNX-4800	Seasonal Prevention of Lyme Disease		Phase 2 field study planned first half 2027 and Phase 2 human challenge study planned 2028 (pending FDA clearances)
TNX-1900	Adolescent Obesity, Binge Eating Disorder, and Bone Health in Pediatric Autism; Social Anxiety Disorder	Phase 2 currently enrolling* Phase 2 clinical phase completed*
TNX-1500	Kidney Transplant Rejection		Phase 2 study planned for mid 2026*
TNX-1500	Kidney Transplant Rejection	Phase 1 topline reported 1Q’25
TNX-1300	Cocaine Intoxication		Mid-Phase 2
TNX-801	Smallpox and Mpox vaccine	Preclinical, pre-IND
TNX-1900	Adolescent Obesity, Binge Eating Disorder, Bone Health in Pediatric Autism, and arginine-vasopressin deficiency		Phase 2 currently enrolling*
TNX-1800	COVID-19 vaccine	Preclinical, pre-IND
TNX-2900	Prader-Willi Syndrome		Phase 2 expected to commence first quarter 2027
TNX-2900	Prader-Willi Syndrome	Phase 2 ready
TNX-801	Smallpox and Mpox vaccine		Preclinical, pre-IND
TNX-4200	Treatment or Prevention of Viral Disease	~~Preclinical, pre-IND~~	Preclinical, pre-IND
TNX-1700	Gastric and colorectal Cancer	Preclinical, pre-IND
TNX-4900	Neuropathic pain		Preclinical, pre-IND
TNX-1700	Gastric and colorectal Cancer		Preclinical, pre-IND

*Investigator Initiated Studies

TNX-102 SL

Overview

TNX-102 SL is a proprietary sublingual tablet formulation of cyclobenzaprine (“CBP”) that efficiently delivers CBP across the oral mucosal membrane into the systemic circulation. TNX-102 SL is approved under the brand name TONMYA, for the treatment of fibromyalgia in the U.S. We have active IND’s for TNX-102 SL as a ~~bedtime~~ treatment for ~~fibromyalgia~~MDD, ASD/ASR, PTSD, ofor multi-site pain associated with Long COVID, AAD and AUD. ~~The~~however, ~~University~~we ofare ~~North~~not ~~Carolina has~~currently anstudying ~~investigator~~TNX-~~initiated~~102 ~~IND~~SL ~~for~~in ~~ASD~~PTSD, ~~that~~AAD, ~~references~~Long ~~our~~Covid ~~INDs~~or AUD. We own all rights to TNX-102 SL in all geographies, and we bear no obligations to third parties for any future development or commercialization. Excipients used in TNX-102 SL are approved for pharmaceutical use. Some of the excipients were specially selected to promote a local oral environment that facilitates transmucosal absorption of CBP.

The current TNX-102 SL sublingual tablets each contain 2.8 mg of CBP. We selected this dose with the goal of providing a balance of efficacy, safety, and tolerability that would be acceptable as a first-line therapy and for long-term use, and in-patient populations characterized by burdensome symptoms and sensitivity to medications.

The active ingredient in TNX-102 SL is CBP, a multi-functional drug that blocks the serotonin-2A, alpha-1 adrenergic, muscarinic M1 and histaminergic H1 receptors.

CBP is a tertiary amine tricyclic, that is the listed active ingredient of two products that are approved in the U.S. for the treatment of muscle spasm: Flexeril® (5 mg and 10 mg oral immediate-release, or IR, tablet) and Amrix^® (15 mg and 30 mg oral extended-release capsule or ER capsule). The Flexeril brand of CBP IR tablet has been discontinued since May 2013. There are numerous generic versions of CBP IR tablets on the market. CBP-containing products are approved for short term use (two to three weeks) only as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions. CBP IR tablets are recommended for three times per day dosing, which results in relatively stable blood levels of CBP after several days of treatment. Extended-release (ER) CBP capsules taken once a day mimic, and flatten, the pharmacokinetic profile of three times per day CBP IR tablets.

Both the IR and ER tablet formulations of CBP result in accumulation of the persistent metabolite norcyclobenzaprine (“norCBP”) to blood levels that exceed the levels of CBP. NorCBP is a secondary amine tricyclic with a relatively stronger inhibitory activity of the norepinephrine transporter (NET) than the parent CBP. We believe that the accumulation of norCBP is undesirable in a medicine to be taken chronically at bedtime because norCBP accumulates over weeks, potentially interfering with the dynamic receptor effects of CBP and also may interrupt sleep quality by inhibiting the NET.

We designed TNX-102 SL to be administered once-daily at bedtime and with the intention for long-term use. We believe the selected ~~dose~~ dose of TNX-102 SL and its unique pharmacokinetic profile will enable it to achieve a desirable balance of efficacy, safety, and tolerability. Our Phase 1 pharmacokinetic comparative trials showed that, on a dose-adjusted basis, TNX-102 SL results in faster systemic absorption and significantly higher plasma levels of CBP in the first hour following sublingual administration relative to to oral IR CBP tablets. It also showed that the sublingual route of administration, which bypasses the “first pass” ~~hepatic~~ hepatic metabolism that swallowed medications undergo, results in a higher plasma level of CBP relative to norcyclobenzaprine ~~during~~ during sleeping hours when taken at bedtime. We believe the dynamic changes in CBP after TNX-102 SL administration at steady state ~~during~~ during chronic use contribute to its activity in treating fibromyalgia. We believe this is the first drug designed to increase the activity of the tertiary amine tricyclic parent and decrease the activity of the secondary amine tricyclic active metabolite. In clinical studies, TNX-102 SL 2.8 mg and TNX-102 SL 5.6 mg were generally well-tolerated, with no drug-related serious and unexpected ~~adverse~~ adverse reactions reported in these studies. The most common adverse event was transient numbness in the mouth after TNX-102 SL administration.

In September 2024, at the 11th Global Conference on Pharmaceutics and Novel Drug Delivery Systems (PDDS 2024), the Company announced data highlighting the proprietary formulation technology and pharmacokinetic properties of TNX-102 SL, including composition and methods patents based on the proprietary eutectic formulation of TNX-102 SL that are expected to provide market exclusivity until at least 2034 in the U.S., EU, Japan, China and other jurisdictions. The eutectic protects cyclobenzaprine HCl from interacting with the basifying agent that is also part of the formulation and required for efficient transmucosal absorption. The formulation of TNX-102 SL was designed specifically for sublingual administration and transmucosal absorption for bedtime dosing to target disturbed sleep, improve pain and other fibromyalgia symptoms, while reducing the risk of daytime somnolence.13

We have successfully completed the pivotal exposure bridging study with TNX-102 SL compared to Amrix. Results from this study support the approval of TNX-102 SL under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (“FDCA”) with Amrix as the listed drug. We believe that TNX-102 SL has the potential to provide clinical benefit in fibromyalgia and PTSD and possibly other CNS indications that are underserved by currently marketed products or have no approved treatment.

We have also successfully completed a bridging pharmacokinetic study in ethnic Japanese and Chinese volunteers that shows similar characteristics to our historical data in Caucasian volunteers. We believe this will satisfy one of the criteria for approval in Japan and China and will allow us to reference the U.S. efficacy data to support marketing applications in those countries.

TNX-102 SL (cyclobenzaprine HCl sublingual tablets) – FM program

We are developing TNX-102 SL as a bedtime treatment for FM.

Clinical Development Plan

NDA Acceptance and PDUFA Goal Date

In October 2024, Tonix submitted its NDA to the FDA for TNX-102 SL 5.6 mg for the management of fibromyalgia and in December 2024, the FDA assigned a PDUFA goal date of August 15, 2025, for a decision on marketing authorization for TNX-102 SL. We are preparing for a commercial launch of TNX-102 SL in the fourth quarter of 2025, conditional on FDA approval.

Pre-NDA Meetings and Fast Track Designation

In July 2024, Tonix was granted Fast Track designation by the FDA for TNX-102 SL for FM. The designation validates that FM is a serious condition and that TNX-102 SL has the potential to address this unmet medical need. Tonix previously announced alignment with the FDA regarding the content of its proposed NDA submission, following completion of the Company’s pre-NDA meetings.

During the second quarter of 2024, Tonix successfully completed two positive pre-NDA meetings with the FDA for TNX-102 SL for the management of fibromyalgia. The first, with minutes announced in June 2024, was a Type B Chemistry, Manufacturing, and Controls (CMC) meeting to seek alignment and agreement with the FDA on key CMC topics to support the planned NDA submission for TNX-102 SL. Based on formal meeting minutes, the Company believes it is aligned with the FDA on proposed drug substance and drug product commercial specifications, shelf life assignment, manufacturing and commercial drug packaging. At the second pre-NDA meeting announced in July 2024, the Company and the FDA aligned on nonclinical, clinical pharmacology and clinical matters and agreed that the proposed data package is sufficient to support the NDA submission.

Completed Phase 3 RESILIENT Study (F307) with Statistically Significant Improvement in Primary Endpoint of Pain Reduction

The first patient was enrolled in the pivotal Phase 3 RESILIENT study in April 2022. The RESILIENT study was a double-blind, randomized, placebo-controlled adaptive design trial designed to evaluate the efficacy and safety of TNX-102 SL in FM. The two-arm trial enrolled 457 participants in the U.S. The first two weeks of treatment consist of a run-in period in which participants start on TNX-102 SL 2.8 mg (1 tablet) or placebo. Thereafter, all participants increase their dose to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks. The RESILIENT study achieved statistical significance on the pre-specified primary efficacy endpoint: change from baseline in the weekly average of daily diary pain severity numerical rating scale (NRS) scores for TNX-102 SL 5.6 mg (LS mean [SE]: -1.8 [0.12] units) versus placebo (-1.2 [0.12] units), analyzed by mixed model repeated measures with multiple imputation (LS mean [SE] difference: -0.7 [0.16] units, p=0.00005). In addition, all pre-specified sensitivity analyses of the primary endpoint were statistically significant (p≤0.001). We observed reduction in pain across all weeks of the 14-week study, with nominal p<0.01 for every week. The rapid onset of action with separation from placebo at Week 1 was sustained throughout all weeks of dosing. TNX-102 SL was well tolerated and consistent with prior trials, with no new safety signals observed. Among participants randomized to the TNX-102 SL and placebo arms, 81.0% and 79.2%, respectively, completed the 14-week dosing period. As expected, based on prior TNX-102 SL studies, administration site reactions were the most commonly reported adverse events and were higher in the TNX-102 SL treatment group. Hypoaesthesia oral and paraesthesia oral, or tongue and mouth numbness or tingling, product taste abnormal (typically a bitter aftertaste upon dosing), and tongue discomfort were local effects nearly always temporally related to dose administration and transiently expressed (<60 minutes) in most occurrences. The only treatment-emergent adverse events that occurred at a rate of 3.0% or greater in either arm were these four oral adverse events, along with COVID-19, somnolence, and headache. Adverse events resulted in premature study discontinuation in 6.1% of those who received TNX-102 SL compared with 3.5% of placebo recipients. There were a total of seven serious adverse events in five patients, five of which were experienced by three patients in the placebo arm, and two of which were in the TNX-102 SL arm. Of the two in the TNX-102 SL arm, one was renal cancer, deemed unrelated to study drug, and the other was acute pancreatitis with onset 14 days after dosing was completed, reported as possibly related to study drug, and was resolved before the final study visit.

Completed Phase 3 RALLY Study (F306)

The RALLY study was a double-blind, randomized, placebo-controlled adaptive design trial intended to evaluate the efficacy and safety of TNX-102 SL in FM. The trial was designed to enroll approximately 670 patients across approximately 40 U.S. sites. For the first two weeks of treatment, there was a run-in period in which patients started on TNX-102 SL 2.8 mg (1 tablet) or placebo. After the first two weeks, all patients had the dose increased to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for 12 weeks. The primary endpoint was daily diary pain severity score change from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation. We reported pre-planned interim analysis results from a Phase 3 study, RALLY (F306), in July 2021. Based on the recommendation from the independent data monitoring committee that the RALLY trial was unlikely to demonstrate a statistically significant improvement in the primary endpoint, we stopped enrollment of new participants but allowed those participants who were already enrolled to complete the study. We reported topline data from the completed study in March of 2022. As expected, based on interim analysis results, TNX-102 SL did not achieve statistical significance over placebo on the primary endpoint of reduction in daily pain. Relative to the previous positive Phase 3 Study (RELIEF), RALLY had an unexpected increase in study participant adverse event-related discontinuations in both drug and placebo groups (~80% higher in each), which we believe may have been impacted by conducting the study in the period of highest mortality across the U.S. from the COVID-19 pandemic (September 2020 through March 2021 for the interim analysis sample).

Completed Phase 3 RELIEF Study (F304) with Statistically Significant Improvement in Primary Endpoint of Pain Reduction

In the fourth quarter of 2020, we announced the results of a randomized, double-blind, placebo-controlled, 12-week Phase 3 study of TNX-102 SL in 503 participants with FM, which we refer to as the RELIEF study. The primary objective of this study was to evaluate the potential clinical benefit of using TNX-102 SL to treat FM at a dose of 5.6 mg, administered sublingually once daily at bedtime for 12 weeks. The primary endpoint of the RELIEF trial was the daily diary pain severity score change from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation. The RELIEF study achieved statistical significance on the primary efficacy endpoint: change from baseline in the weekly average of daily diary pain severity numerical rating scale (NRS) scores for TNX-102 SL 5.6 mg (LS mean [SE]: -1.9 [0.12] units) versus placebo (-1.5 [0.12] units), analyzed by mixed model repeated measures with multiple imputation (LS mean [SE] difference: -0.4 [0.16] units, p=0.010).

The statistically significant improvement in pain is further substantiated when diary pain was analyzed by another standard statistical approach, a 30 percent responder analysis, with 46.8% on active and 34.9% on placebo having a 30 percent or greater reduction in pain (logistic regression; odds ratio [95% CI]: 1.67 [1.16, 2.40]; p=0.006, uncorrected). Consistent with the proposed mechanism that TNX-102 SL acts in fibromyalgia through improving sleep quality, TNX-102 SL showed nominal improvement of sleep by several measures. For daily diary sleep quality ratings, TNX-102 SL (-2.0 [0.12] units) compared to placebo (-1.5 [0.12] units) was nominally significant (LS mean difference: -0.6 [0.17] units; p<0.001). For the PROMIS Sleep Disturbance instrument, TNX-102 SL was also nominally significant over placebo on T-scores (LS mean difference: -2.9 [0.82] units; p<0.001). The effect sizes on the diary sleep quality ratings and PROMIS Sleep Disturbance instrument were 0.31 and 0.32, respectively.

In the RELIEF study, TNX-102 SL was similarly well tolerated as in the prior Phase 2 BESTFIT and Phase 3 AFFIRM studies, which both studied TNX-102 SL at a lower dose of 2.8 mg daily. There were no new safety signals observed in the RELIEF study at the 5.6 mg daily dose. Among participants randomized to the TNX-102 SL and placebo arms, 82.3% and 83.5%, respectively, completed the 14-week dosing period. As expected, based on prior studies, administration site reactions are the most commonly reported adverse events and were higher in the TNX-102 SL treatment group, including rates of hypoaesthesia oral (17.3% vs. 0.8%), oral pain/discomfort (11.7% v. 2.0%), product taste abnormal (6.5% vs. 0.4%), and paraesthesia oral (5.6% v. 0.4%). Hypoaesthesia or paraesthesia oral and product taste abnormal were local administration site effects nearly always temporally related to dose administration and transiently expressed (<60 minutes) in most occurrences. The only systemic treatment-emergent adverse events that occurred at a rate of 5.0% or greater in either arm was somnolence/sedation at 5.6% in the TNX-102 SL arm vs. 1.2% in placebo, which was consistent with known side effects of marketed oral cyclobenzaprine. Adverse events resulted in premature study discontinuation in 8.9% of those who received TNX-102 SL compared with 3.9% of placebo recipients. There was a total of seven serious adverse events reported during the study, none of which were deemed related to investigational product; five in placebo arm, and two in TNX-102 SL arm. Of the two in the TNX-102 SL arm, one was a motor vehicle accident with multiple bone fractures, and the other was a case of pneumonia secondary to an infection.

Global NDA Requirements

We are planning to develop TNX-102 SL for the treatment of FM in the UK, Europe and Japan. ~~Cyclobenzaprine,~~ ~~the~~We ~~active~~plan ~~ingredient~~to discuss the development of TNX-102 SL, ~~has~~for ~~not~~the ~~been~~treatment ~~approved~~of inFM ~~Japan,~~with ~~and~~the isUK’s ~~considered~~Medicines aand ~~new~~Healthcare ~~chemical~~products ~~entity~~Regulatory Agency (~~NCE~~MHRA)~~. In~~, ~~February~~the ~~2022,~~European weMedicines ~~held~~Agency an(EMA) ~~End~~and ~~of Phase 2 Consultation with~~ the Japanese Pharmaceuticals and Medical Devices Agency, or (PMDA). Cyclobenzaprine, anthe ~~independent~~active ~~administrative institution~~ingredient ~~responsible~~of ~~for~~TNX-102 ~~ensuring the safety~~SL, ~~efficacy~~has ~~and~~not ~~quality~~been ofapproved ~~pharmaceuticals~~in ~~and~~the UK, ~~medical~~most ~~devices~~countries in ~~Japan~~Europe, toor ~~discuss~~in ~~the~~ Japan ~~development plan~~. ~~Agreement~~In ~~was~~February ~~reached~~2022, onwe ~~the~~held ~~design~~an End of a Phase 12 ~~bridging~~Consultation ~~study~~with ~~(TNX-CY-F108/F108)~~the ~~in ethnic~~ Japanese ~~healthy volunteers~~PMDA, to discuss ~~enable~~the ~~clinical~~potential ~~studies~~Japan ofdevelopment ~~TNX-102 SL in Japan~~plan. PMDA ~~also~~has provided guidance on the overall nonclinical package to support a Japan NDA filing for TNX-102 SL for the treatment of FM. We plan to have another Consultation with PMDA to provide program updates and discuss the Japan development plan.

18We have also successfully completed a Phase 1 bridging pharmacokinetic study in ethnic Japanese and Chinese volunteers that shows similar characteristics to our historical data in Caucasian volunteers. We believe this will satisfy one of the criteria for approval in Japan and China and will allow us to reference the U.S. efficacy data to support marketing applications in those countries.

~~The~~A ~~F108~~ Phase 1 PK study was initiated in March 2022 and the clinical phase was completed in May 2022. Since the similarity in PK profile between people of Japanese and Chinese descent was confirmed, the PK data from the two ethnic groups were pooled as for Asian data (n=20) and compared retrospectively with the Caucasian study data from Study TNX-CY-F110 (n=16). The Asian/Caucasian geometric mean ratios of cyclobenzaprine Cmax, AUC0-T and AUC0-∞ were between 0.9 and 1.11 after both the 5.6 mg dose and the 2.8 mg dose. The 90% CI of Asian/Caucasian geometric mean ratios for Cmax, AUC0-T and AUC0-∞, were all within the formal narrow equivalence limit of 0.8 to 1.25 after both the 5.6 mg dose and 2.8 mg dose, respectively. These results support similarity in cyclobenzaprine PK between Asian (pooled Japanese and Chinese) and Caucasian samples.

~~Long~~TNX-~~Term~~102 ~~Safety~~SL ~~Exposure~~(cyclobenzaprine ~~Study~~HCl ~~for~~sublingual ~~TNX-102~~tablets) SL– Major Depressive Disorder (MDD) Program

~~In October 2019, we completed long-term safety exposure studies in participants~~We ~~with~~are ~~PTSD~~developing ~~to evaluate the tolerability of~~ TNX-102 SL ~~5.6~~as mga totreatment ~~support an NDA~~ for ~~the~~MDD. ~~treatment~~In ofSeptember ~~PTSD. The~~2025, ~~data~~Tonix ~~provide~~announced usthe ~~with exposure~~successful ~~data~~completion of ~~daily~~a ~~dosing~~Type ofB ~~TNX~~Pre-~~102~~IND meeting SLwith ~~5.6~~the mgFDA ~~for~~regarding atthe ~~least~~development ~~12 months in more than 50 individuals, and daily dosing~~ of TNX-102 SL ~~5.6~~ mg for atthe ~~least~~treatment 6of ~~months~~MDD. inThe ~~more~~Company ~~than~~received ~~100~~positive ~~individuals.~~feedback from ~~The~~the ~~data~~FDA ~~was~~and ~~collected~~plans into ~~open-label~~pursue ~~extension~~a ~~studies~~supplemental ofnew ~~the~~drug ~~PTSD~~application ~~program. Based~~(sNDA) onto expand the ~~FDA’s~~ ~~guidance,~~therapeutic ~~the~~indication ~~long~~of TNX-~~term~~102 ~~safety~~SL to ~~exposure~~include ~~studies~~MDD, inbased ~~PTSD~~on ~~was~~exploratory ~~used~~findings tosuggesting ~~support~~that ~~the~~improving ~~NDA~~sleep ~~for~~quality ~~the~~may ~~management~~positively ofimpact ~~fibromyalgia~~depressive symptoms.

~~Manufacturing~~ In November 2025, the FDA cleared the IND application to support clinical development of TNX-102 SL 5.6 mg for the treatment of MDD in adults. The unique pharmacological profile of TNX-102 SL is designed to target the disruptive sleep which is often associated with depression. Prior studies of TNX-102 SL in fibromyalgia and post-traumatic stress disorder (PTSD) showed promising signals for improvement of depressive symptoms on the Beck Depression Inventory-II and the MADRS, respectively.

~~TNX-102 SL~~The ~~drug~~IND ~~product~~clearance ~~for~~enables ~~Phase~~Tonix 3to ~~and~~proceed ~~the~~with ~~associated~~a ~~registration~~potentially ~~batches~~pivotal ~~for~~Phase 2 ~~the~~HORIZON ~~NDA~~study, ~~were~~a ~~manufactured~~6-week, atrandomized, ~~commercial~~double-blind, ~~cGMP facilities. We currently have 36~~placebo-~~month~~controlled ~~stability~~study ~~data~~of ~~in the proposed packaging configurations ready for commercialization. The FDA has reviewed the proposed CMC data package to support~~ TNX-102 SL’s ~~NDA~~as ~~approval~~a ~~and~~first-line ~~commercial~~monotherapy ~~manufacturing~~in ~~plans~~adults ~~as part of the IND~~with ~~process~~MDD. ~~Tonix~~About is360 ~~ready~~patients towill ~~manufacture~~be ~~TNX-102~~enrolled SLat ~~commercial~~approximately ~~product~~30 ~~for~~U.S. ~~the forecasted fibromyalgia market~~sites. ~~During~~ ~~the second~~Eligible ~~quarter~~participants ofare ~~2024,~~18 ~~Tonix~~years ~~successfully~~or ~~completed~~older aand ~~pre-NDA~~currently ~~meeting with the FDA for TNX-102 SL for~~ experiencing a ~~Type~~moderate ~~B Chemistry, Manufacturing, and Controls (CMC) meeting~~ to ~~seek~~severe ~~alignment~~major ~~and~~depressive ~~agreement~~episode. ~~with~~The ~~the~~study ~~FDA~~will oncompare ~~key CMC topics to support the planned NDA submission for~~ TNX-102 SL 5.6 ~~Based on formal meeting minutes~~mg, ~~the~~taken ~~Company~~sublingually ~~believes~~at itbedtime isto ~~aligned~~placebo, with the ~~FDA~~primary onendpoint ~~proposed~~being ~~drug~~the ~~substance~~MADRS ~~and drug~~total ~~product~~score ~~commercial~~change ~~specifications,~~from ~~shelf~~baseline ~~life~~at ~~assignment,~~Week ~~manufacturing~~6. ~~and~~Secondary ~~commercial~~endpoints ~~drug~~include ~~packaging.~~global Inimpression ~~March 2024~~scores, ~~Tonix~~ ~~announced~~anxiety ~~it selected two contract manufacturing organizations (CMOs)~~ratings, ~~one~~and measures of ~~which~~sleep isdisturbance. ~~Almac~~Tonix ~~Pharma~~plans ~~Services,~~to ainitiate ~~member~~enrollment of the ~~privately~~ ~~owned~~study ~~Almac~~in ~~Group, as dual supply sources for the potential launch and commercialization of TNX~~mid-~~102~~year ~~SL in the U~~2026.S.

TNX-102 SL – Acute Stress Disorder Program

TNX-102 SL is being developed as a bedtime treatment for ASR/ASD in collaboration with the University of North Carolina under an investigator-initiated IND.

Phase 2 OASIS Study

This investigator-initiated study ~~will~~is bebeing conducted by the University of North Carolina Institute for Trauma Recovery. The University of North Carolina has been awarded a $3 million grant from the DoD to investigate the potential of Tonix’s TNX-102 SL to reduce the frequency and severity of adverse effects of acute trauma. The proposed Optimizing Acute Stress reaction Interventions with TNX-102 SL (OASIS) trial will examine the safety and efficacy of TNX-102 SL to reduce adverse posttraumatic neuropsychiatric sequelae among patients presenting to the emergency department (“ED”) after a motor vehicle collision. The investigator-initiated trial ~~will~~was commenced in May 2025 and is targeting to enroll approximately 180 individuals who acutely experienced trauma at ED study sites across the U.S. and participants will be randomized in the ED to receive a two-week course of either TNX-102 SL or placebo. ~~We expect enrollment in the OASIS study to begin in the first half of 2025.~~ The OASIS trial will examine the safety and efficacy of TNX-102 SL to reduce adverse posttraumatic neuropsychiatric sequelae among patients in the ED after a motor vehicle collision. A fourteen -day course of bedtime TNX-102 SL will be tested in the immediate aftermath of motor vehicle collision trauma. The study will test the potential for TNX-102 SL to target trauma-related sleep disturbance and its ability to facilitate recovery from ASR and to prevent PTSD. The results, if positive, may ultimately provide military personnel with a new treatment option that, when administered in the early aftermath of a traumatic event to individuals with ASR symptoms, improves warfighter function.

The OASIS trial will build upon a foundation of knowledge and infrastructure developed through the University of North Carolina-led, $40 million AURORA initiative. The AURORA study is a major national research initiative to improve the understanding, prevention, and recovery of individuals who have experienced a traumatic event. AURORA is supported by funding from the NIH, leading brain health nonprofit One Mind, private foundations, and partnerships with leading tech companies such as Mindstrong Health and Verily Life Sciences, the health care arm of Google’s parent company Alphabet. 14

19The OASIS trial will build upon a foundation of knowledge and infrastructure developed through the University of North Carolina-led, $40 million AURORA study. The AURORA study is a major national research initiative to improve the understanding, prevention, and recovery of individuals who have experienced a traumatic event. AURORA is supported by funding from the NIH, leading brain health nonprofit One Mind, private foundations, and partnerships with leading tech companies such as Mindstrong Health and Verily Life Sciences, the health care arm of Google’s parent company Alphabet.

~~Initiation~~We presented clinical data and rationale supporting the potential for TNX-102 SL to be studied for the treatment of ~~patient~~ASR ~~enrollment~~and prevention of PTSD. Prior studies showed that treatment with TNX-102 SL showed effects on sleep and PTSD symptoms in PTSD patients at two and four weeks. This supportive data on the ~~proposed~~effects ~~investigator~~of ~~sponsored~~TNX-102 ~~OASIS~~SL ~~trial~~on isreducing ~~anticipated~~PTSD insymptoms suggest early intervention immediately after trauma using TNX-102 SL has the ~~first~~potential to ~~half~~reduce ASR and to be prophylactic for development of ~~2025~~ASD and PTSD. ~~The~~Data ~~FDA~~from these trials support testing of TNX-102 SL within 24 hours ~~granted~~of ~~IND~~index ~~clearance~~trauma infor effects on ASR symptoms and the ~~first~~subsequent ~~quarter~~incidence of ~~2024~~newly developed ASD within one month and PTSD after one month from the index trauma.

~~In August 2024 at the DoD’s MHSRS conference, the Company presented clinical data and rationale supporting the potential for~~ TNX-~~102 SL to be studied for the treatment of ASR and prevention of PTSD. Prior~~4800 ~~studies~~– ~~showed~~Lyme ~~that~~Disease treatment with TNX-102 SL showed effects on sleep and PTSD symptoms in PTSD patients at two and four weeks. This supportive data on the effects of TNX-102 SL on reducing PTSD symptoms suggest early intervention immediately after trauma using TNX-102 SL has the potential to reduce ASR/ASD symptoms which are similar to those of PTSD. Data from these trials support testing of TNX-102 SL within 24 hours of index trauma for effects on ASR symptoms and the subsequent incidence of newly developed PTSD.Prophylaxis

TNX-4800 (formerly known as mAb 2217LS) is a humanized monoclonal antibody with an engineered extended half-life that targets the outer-surface protein A (OspA) on Lyme-causing Borrelia bacteria. By binding OspA when TNX-4800 containing blood is ingested by the tick, TNX-4800 kills and blocks the maturation of Borrelia burgdorferi in the mid-gut of infected deer ticks. Published work in animals showed that TNX-4800 was 95% effective in preventing infection after 6 days of exposure to ticks infected with Borrelia burgdorferi. TNX-4800 was derived from mAb 2217 by amino acid substitutions in its crystallizable fragment (Fc) domain which served to prolong the serum half-life. A single administration in the Spring is designed to provide onset of immunity within two days and maintain protective antibody titers for the entire tick season, providing pre-exposure prophylaxis against Lyme disease without relying on the recipient’s immune system to generate antibodies. By delivering a well-characterized antibody directly, TNX-4800 has been shown to block transmission of the major Borrelia genospecies from ticks to pre-treated animals. TNX-4800 also sidesteps the multidose schedules required for OspA vaccines in development and the FDA-approved vaccine that was withdrawn from the market. Tonix intends to advance TNX-4800 through additional clinical trials with the goal of submitting a Biologics Licensing Application (BLA) to the FDA.

TNX-4800 was studied in a randomized, double-blind, sequential dose-escalation phase 1 study (NCT04863287) that evaluated safety, tolerability, pharmacokinetics (PK), and immunogenicity of TNX-4800 in healthy adults. Forty-four subjects were randomized and 41 completed the study. Subjects received a single subcutaneous (SC) administration of placebo or TNX-4800 at 0.5, 1.5, 5, or 10 mg/kg. Safety was assessed via clinical and lab evaluations. Drug exposure increased by approximately 25-times for a 20-times increase in dose. Serum TNX-4800 was measurable at the earliest sampling time of 24 hours, indicating rapid systemic absorption. TNX-4800 concentrations remained quantifiable for >200 days in 80% of volunteers at the lowest dose and for up to 350 days in the majority of volunteers at higher doses (i.e., ≥ 1.5 mg/kg). Mean half-life ranged from 62–69 days across groups. Serum concentrations remained quantifiable for up to 12 months in most subjects. Mean exposure for the 10 mg/kg cohort was less than 20% of the highest exposures in a rat toxicology study. Anti-drug antibodies (ADA) were detected in <10% of treated subjects, with no impact on PK. Most adverse events were mild or moderate. TNX-4800 was determined to be generally safe and well tolerated.

In infected deer ticks, Borrelia’s OspA lipoprotein binds to tick-gut receptor TROSPA and helps it adhere to the midgut lining. During a tick bite blood meal, Borrelia downregulates OspA, upregulates OspC, and activates motility genes. Borrelia undergoes a metamorphic-like transformation, becoming highly flagellated and mobile, which facilitates migration to the tick salivary glands and invasion of human host tissues. During a tick bite of an animal pre-treated with TNX-4800, the tick ingests host blood containing TNX-4800, which kills and blocks the metamorphic-like transformation of Borrelia in the tick’s midgut preventing transmission of the bacteria. Lyme-causing Borrelia-exposed or -infected individuals, rarely make antibodies against OspA which allows for people to be reinfected despite having immunity to OspC. Consequently, we expect that protection against Borrelia would require annual prophylaxis with TNX-4800.

TNX-1500 – Organ Transplant Rejection/Autoimmune Conditions

TNX-1500 is a humanized mAb directed against CD40-ligand, or CD40L (also known as CD154), engineered to modulate binding to Fc receptors. TNX-1500 is being developed for the prevention of allograft and xenograft rejection, for the prevention of graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation (HCT) and for the treatment of autoimmune diseases. The IND was cleared for the prevention of kidney transplant. TNX-1500 incorporates the antigen binding fragment (Fab) region of hu5c8, which has been extensively characterized including at the atomic level in complex with CD40-ligand.

CD40-ligand is a protein expressed on the surface of activated T lymphocytes that mediates T cell helper function. CD40-ligand is also known as CD154, the T cell-B cell activating molecule (T-BAM), TRAP and gp39. CD154 is a member of the Tumor Necrosis Factor (TNF) Super Family. No mAb against CD154 has been approved for commercial use anywhere in the world. Other TNF Super Family members have been successfully targeted by antagonist mAbs. Approved mAbs against TNFα include: infliximab (Remicade®), adalimumab (Humira®), certolizumab pegol (Cimzia®), and golimumab (Simponi®) for the treatment of certain autoimmune conditions. Also, etanercept (Enbrel®) is a TNFα antagonist receptor fusion protein. An approved mAb against RANKL (CD254) is denosumab (Prolia® or Xgeva®) for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.

The Fc-modified TNX-1500 has shown activity and has been well tolerated in animals and in a single dose Phase 1 pharmacodynamic (PD) and pharmacokinetic (PK) study that supports monthly dosing. TNX-1500 was engineered to modulate binding to Fc receptors with the goal of maintaining the activity of first-generation monoclonal antibodies (mAbs), yet with reduced risk of thrombotic complications. TNX-1500 is being developed as a prophylaxis against organ transplant rejection as well as to treat autoimmune conditions. A Phase 1 single ascending dose escalation study of TNX-1500 at 3 mg/kg, 10 mg/kg and 30 mg/kg of TNX-1500 in healthy volunteers was initiated in the second quarter of 2023. The objectives of the Phase 1 trial were to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenous TNX-1500, as well as to support dosing in a planned Phase 2 trial in kidney transplant recipients. We reported positive topline data related to the Phase 1 in February of 2025. TNX-1500 showed suppression of the primary and secondary antibody responses to KLH antigen challenges for the 10 and 30 mg/kg doses. Additionally, preliminary pharmacokinetic results showed mean half-life (t_1/2) for the 10 mg/kg and 30 mg/kg dose groups of 34-38 days, consistent with monthly dosing. In healthy volunteers, TNX-1500 was generally well-tolerated. Anti-CD40L has multiple potential indications in addition to solid organ and bone marrow transplantation including autoimmune diseases.

In pre-clinical experiments at MGH, TNX-1500 has been studied as monotherapy or in combination with immunosuppressive drugs in heart and kidney organ transplants in animals. The data demonstrates that TNX-1500 showed activity in preventing organ rejection and was well tolerated in animals. Blockade of CD40L with TNX-1500 monotherapy consistently prevented pathologic alloreactive in animal models of cardiac and kidney allograft model without evidence of clinical thrombosis.

In November 2025, we entered into a collaboration with MGH, a founding member of Mass General Brigham (MGB) to conduct an investigator-initiated Phase 2 clinical trial evaluating TNX-1500 in kidney transplant recipients. The study will be led by Ayman Al Jurdi, M.D., at MGH and is designed to assess the safety, tolerability and activity of Fc-modified anti-CD40L mAb TNX-1500 in preventing kidney transplant rejection while significantly minimizing the dose of conventional immunosuppressive drugs, which are associated with infection, cancer, cardiovascular side effects and various metabolic derangements. The CD40 ligand (CD40L) is also known as CD154. Study initiation is contingent on institutional review board (“IRB”) approval and FDA clearance of an investigator-initiated IND. Pending IRB approval and IND clearance, the open-label, single-center study will enroll five adult kidney transplant recipients at MGH. Patients will receive induction therapy with anti-thymocyte globulin, TNX-1500, tacrolimus, and corticosteroids. The corticosteroids will be tapered and discontinued by Day 33 post-transplant. TNX-1500 will be continued for 12 months (to the primary endpoint) with an option to continue treatment beyond 12 months. Tacrolimus at standard dose will be continued for six months, at which point tacrolimus will be decreased to low dose with the expectation of discontinuing tacrolimus after 12 months. The primary endpoint is the incidence of adverse and serious adverse events at 12 months. Secondary endpoints include graft survival, renal function, biopsy-proven acute rejection, and incidence of donor-specific antibodies. The study is expected to be initiated mid-2026.

Data published in two peer reviewed articles in the American Journal of Transplantation demonstrate TNX-1500 prevents rejection, prolongs survival and preserves graft function as a single agent or in combination with other drugs in animal renal and heart allografts

TNX-1300 – Cocaine Intoxication

TNX-1300 (T172R/G173Q double-mutant cocaine esterase 200 mg, i.v. solution) is being developed for the treatment of cocaine intoxication. TNX-1300 is a recombinant protein enzyme produced through rDNA technology in a non-disease-producing strain of E. coli bacteria. Cocaine Esterase (“CocE”) was identified in bacteria (Rhodococcus) that use cocaine as the sole source of carbon and nitrogen and ~~that~~ that grow in soil surrounding coca plants. The gene encoding CocE was identified and the protein was extensively characterized. CocE catalyzes the breakdown of cocaine into metabolite ecgonine methyl ester and benzoic acid. Wild-type CocE is unstable at body temperature, so targeted mutations were introduced in the CocE gene and resulted in the T172R/G173Q double-mutant CocE, which is active for approximately 6 hours at body temperature.

Currently there is no specific pharmacotherapy indicated for cocaine intoxication, a state characterized by acute agitation, hyperthermia, tachycardia, arrhythmias, and hypertension, with the potential life-threatening sequalae of myocardial infarction, cerebrovascular accident, rhabdomyolysis, respiratory failure, and seizures. Patients are currently managed only by supportive care for the adverse effects of cocaine overdose on the cardiovascular and central nervous systems. By targeting the cause of cocaine intoxication, rather than the symptoms like other medicines in emergency usage, we believe TNX-1300 may offer significant advantages to the current standard of care for cocaine overdose. TNX-1300 was developed by Columbia University, University of Kentucky and University of Michigan, and in-licensed by Tonix from Columbia University in 2019.

In a Phase 2 randomized, double-blind, placebo-controlled clinical study, TNX-1300 at 100 mg or 200 mg i.v. doses was well tolerated and interrupted cocaine effects after cocaine 50 mg i.v. challenge.

In August 2022, we announced that we received a Cooperative Agreement grant from NIDA, part of NIH, to support development of TNX-1300. A positive Phase 2a study of volunteer cocaine users in a controlled laboratory setting has been previously completed. TNX-1300 has been granted Breakthrough Therapy designation by the FDA.

As a biologic and new molecular entity, TNX-1300 is eligible for 12 years of U.S. market exclusivity upon approval by the FDA, in addition to expected patent protection through 2029. Since in-licensing, Tonix has requalified existing inventory, developed a lyophilized drug product to facilitate enhanced stability and handling conditions applicable for an ER treatment, updated the process and analytical methods to current standards and manufactured Phase 2 drug product clinical supply.

We initiated a Phase 2 clinical trial, CATALYST, of TNX-1300 in the third quarter of 2024. The Phase 2 trial iswas a single-blind, placebo-controlled, proof-of-concept study comparing the safety of a single 200 mg dose of TNX-1300 to standard of care alone in approximately 60 emergency department (ED) patients presenting with cocaine intoxication. Because of the challenges of recruiting eligible patients into ~~this~~a Phase 2 study, we ~~are~~terminated ~~not~~that ~~guiding~~study and intend to ameet ~~timeline~~with the FDA ~~for~~in ~~completion~~2026 to inform the clinical design of ~~enrollment~~our ornext ~~topline~~Phase ~~data~~2 study.

TNX-1900 –Adolescent Obesity, Binge Eating Disorder., ~~Social Anxiety and~~ Bone Health in Pediatric Autism, and Arginine-Vasopressin Deficiency

TNX-1900 (intranasal potentiated oxytocin) is a proprietary formulation of oxytocin primarily in development under investigator-initiated INDs for the treatment of adolescent obesity, binge eating disorder, bone health in pediatric autism, , and ~~social~~arginine-vasopressin ~~anxiety disorder~~deficiency. In 2020, TNX-1900 was acquired from Trigemina, Inc. and licensed from Stanford University. TNX-1900 is a drug-device combination product, based on an intranasal actuator device that delivers oxytocin into the nose.

Oxytocin is a naturally occurring human hormone that acts as a neurotransmitter in the brain. Oxytocin has no recognized addiction potential. It has been observed that low oxytocin levels in the body can lead to an increase in migraine headache frequency, and that increased oxytocin levels can relieve migraine headaches. Certain other chronic pain conditions are also associated with decreased oxytocin levels.

With TNX-1900, the addition of magnesium to the oxytocin formula enhances oxytocin receptor binding as well as its effects on trigeminal neurons and craniofacial analgesic effects in animal models. Intranasal oxytocin has been well tolerated in several clinical trials in both adults and children.

There are ~~three~~four ongoing Phase 2 investigator-initiated studies enrolling at MGH: the POWER study for the treatment of adolescent obesity, the STROBE study for the treatment of ~~BED,~~binge ~~and~~eating disorder, the BOX study for the treatment of bone health in pediatric autism., Inand ~~addition to~~ the ~~studies~~FOCUS atstudy ~~MGH,~~for ~~University~~the oftreatment ~~Washington is conducting an investigator-initiated study~~ of ~~TNX~~arginine-~~1900~~vasopressin ~~in SAD using functional MRI, in which the clinical phase has been completed, and data analyses are in progress~~deficiency.

TNX-~~1500~~ 2900 – ~~Organ~~Prader-Willi Syndrome ~~Transplant~~(PWS) ~~Rejection/Autoimmune Conditions~~

TNX-~~1500~~ 2900 is abased ~~humanized~~on ~~mAb~~our ~~directed~~patented ~~against~~intranasal ~~CD40~~potentiated oxytocin formulation, or TNX-~~ligand~~1900, orbut ~~CD40L~~being ~~(also~~developed ~~known~~for asPWS. ~~CD154),~~We ~~engineered~~licensed totechnology ~~modulate~~using ~~binding~~oxytocin-based therapeutics for the treatment of PWS and non-organic failure to Fcthrive ~~receptors~~disease from Inserm. The licensing agreement has been negotiated and signed by Inserm Transfert, the private subsidiary ~~that~~of isInserm, ~~being~~on ~~developed~~behalf toof ~~prevent~~Inserm, Aix-Marseille Université and ~~treat~~Centre ~~organ~~Hospitalier ~~transplant~~Universitaire ~~rejection~~of asToulouse. ~~well~~PWS is recognized as tothe most ~~treat~~common ~~autoimmune~~genetic ~~conditions.~~cause ~~TNX~~of life-~~1500~~threatening ~~incorporates~~childhood obesity and affects males and females with equal frequency and all races and ethnicities. There is currently no approved treatment for either the ~~antigen~~suckling ~~binding~~deficit ~~fragment~~in ~~(Fab)~~infants ~~region~~or ofthe ~~hu5c8~~obesity and hyperphagia in older children associated with PWS. Since PWS is an orphan disease that occurs in approximately one in 10,000 ~~which~~to 1 in 30,000 births, TNX-2900 for PWS has been ~~extensively~~granted ~~characterized~~Orphan ~~including~~Drug Designation atand Rare Pediatric Disease Designation by the ~~atomic~~FDA. ~~level~~Tonix completed a pre-IND meeting with the FDA in November 2022 to discuss ~~complex~~the ~~with~~most ~~CD40~~efficient and appropriate investigational plan to establish the safety and effectiveness evidence to support the approval of TNX-~~ligand~~2900, and Tonix has received IND clearance.

~~TNX-1500 was~~The ~~engineered~~mechanisms toinvolved ~~modulate~~in ~~binding to Fc receptors with the goal of maintaining the~~ suckling activity ofrequired first-generation monoclonal antibodies (mAbs), yet with reduced risk of thrombotic complications. TNX-1500 is being developed as a prophylaxis against organ transplant rejection as well as to treat autoimmune conditions. The IND was cleared for ~~the~~normal ~~prevention~~feeding ~~of kidney transplant,~~ and athe ~~Phase 1~~role ~~single ascending dose escalation study at 3 mg/kg, 10 mg/kg and 30 mg/kg~~ of ~~TNX-1500~~oxytocin insystem ~~healthy volunteers was initiated~~ in ~~the~~ ~~second~~this ~~quarter~~process ofwill ~~2023~~be investigated. The ~~objectives~~results of ~~the~~this ~~Phase~~work ~~1 trial were to assess the safety, tolerability, pharmacokinetics, and~~are ~~pharmacodynamics~~expected ~~of intravenous TNX-1500, as well as~~ to ~~support~~be ~~dosing~~useful in ~~a planned Phase 2 trial in kidney transplant recipients. We reported positive topline data related to~~ the ~~Phase~~clinical 1care ~~in February~~ of ~~2025.~~infants ~~TNX-1500~~requiring ~~showed~~support ~~suppression of the primary and secondary antibody responses~~ to ~~KLH~~achieve ~~antigen~~efficient ~~challenges~~suckling ~~for the 10 and 30 mg/kg doses~~behavior. ~~Additionally,~~Intranasal ~~preliminary~~oxytocin pharmacokinetic results showed mean half-life (t1/2) for the 10 mg/kg and 30 mg/kg dose groups of 34-38 days, consistent with monthly dosing. In healthy volunteers, TNX-1500 was generally well-tolerated with a favorable safety profile. Anti-CD40L has ~~multiple~~ ~~potential~~previously ~~indications~~been inshown ~~addition~~ to ~~solid~~improve ~~organ~~suckling ~~and bone marrow transplantation including autoimmune diseases: potential pipeline~~ in anewborn ~~product.~~animals ~~Tonix~~and ~~plans~~suppress tofeeding ~~discuss~~behaviors ~~these results with the FDA~~ in anadult ~~End-of-Phase~~animal ~~1 meeting~~models. ~~Pending alignment with the FDA, a Phase 2 study of TNX-1500 in kidney transplant recipients will be pursued.~~

~~TNX-1500~~Research suggests ~~has~~PWS ~~also~~is ~~been~~associated ~~studied in combination~~ with ~~other~~a ~~immunosuppressive agents~~functional indeficiency ~~allogeneic~~of ~~transplants in non-human primates at MGH. In experiments at MGH~~oxytocin, ~~TNX-1500~~a isneuropeptide ~~being~~that ~~studied~~regulates assatiety ~~monotherapy~~and orfeeding inbehaviors ~~combination~~through ~~with~~the ~~other~~oxytocin ~~immunosuppressive~~receptor. ~~agents~~Oxytocin intreatment ~~heart~~addresses ~~and~~several ~~kidney~~key ~~allogeneic~~features ~~organ~~of ~~transplants~~PWS expressed in ~~non~~the MAGEL2 (MAGE-~~human~~like ~~primates~~2) knock-out mouse. Intranasal ~~Results~~oxytocin ~~from~~therapy ~~experiments~~has ~~in kidney~~shown ~~and~~benefits ~~heart~~in ~~transplants~~infants ~~indicate~~with ~~that~~PWS. Carbetocin ~~TNX-1500~~has ~~appears~~a todifferent ~~have~~spectrum ~~comparable~~of ~~efficacy to historical experiments using the chimeric mouse/human~~activity ~~IgG1~~on ~~version~~oxytocin ~~(5c8H1)~~and ofvasopressin ~~the~~receptors ~~anti-CD40L~~than ~~mAb 5c8~~oxytocin. Oxytocin ~~Some~~has ~~results from this collaboration were published in the peer~~dose-~~reviewed~~related ~~journal,~~inconsistencies ~~American Journal of Transplantation~~ in ~~2023. In~~receptor ~~June~~activity ~~2024,~~that athave ~~the~~been described ~~American~~as ~~Transplant~~“high-dose ~~Congress~~suppression” ~~2024,~~or ~~Tonix~~an ~~announced~~“inverted ~~data~~“U” ~~demonstrating the~~dose ~~combined use of~~ response. TNX-~~1500~~2900 ~~and anti-CD28 monoclonal antibody, VEL-101~~ is ~~associated~~formulated with magnesium ~~durable~~to ~~protection~~further ~~and~~enhance ~~graft~~oxytocin ~~survival~~receptor binding and ~~function in~~signaling, awith ~~nonhuman~~the ~~primate~~goal ~~model.~~of ~~Further~~providing ~~data~~more ~~demonstrated~~consistent ~~that~~and ~~TNX-1500~~selective ~~has~~receptor activation ~~promise~~while tominimizing ~~prevent rejection of 9~~off-,target orvasopressin ~~10-gene-edited (GE) pig hearts~~effects. In ~~All~~vitro and in ~~research~~vivo in ~~has~~animals ~~been~~Mg++- containing ~~directed~~formulations byreduce ~~the~~these ~~faculty of the Center for Transplantation Sciences at Massachusetts General Hospital~~inconsistencies.

21In September 2025, we announced plans to progress its TNX-2900 program for the treatment of PWS into a Phase 2 clinical trial. We plan to conduct a Phase 2 randomized, double-blind, placebo-controlled, parallel-design study to evaluate the safety, tolerability, and efficacy of TNX-2900 in male and female participants with PWS, ages 8 to 17.5 years. Eligible participants will be randomized to receive 12-weeks of treatment with TNX-2900 at one of three dose levels, or placebo, in a 1:1:1:1 ratio. The primary efficacy endpoint will be the change from baseline in the validated Hyperphagia Questionnaire for Clinical Trials (HQ-CT), a widely used measure of hyperphagia severity in PWS. Secondary objectives will include assessments of behavior, caregiver burden, and quality of life measures, as well as safety and tolerability outcomes.

TNX-1500 also is being studied in combination with other immunosuppressive agents in xenogeneic organ transplants in non-human primates at MGH. In some of these studies, genetically engineered (“GE”) pigs in baboon transplants were treated with cold perfused ischemia minimization and a novel costimulation-based immunosuppressive regimen including TNX-1500. The results of these preclinical studies were encouraging and demonstrated the potential of genetically engineered pig hearts in the context of a clinically applicable regimen. The multi-GE pigs were provided by eGenesis and Revivicor. Revivicor is a subsidiary of United Therapeutics. Some results from the collaboration with MGH and eGenesis were published in the peer-reviewed journal, Nature in 2023. In March of 2024, MGH announced the first GE pig kidney transplant into a living recipient supported in part by the pre-clinical work with TNX-1500. TNX-1500 therapy was not used in the human transplant recipient.

In pre-clinical experiments at MGH, TNX-1500 is being studied as monotherapy or in combination with immunosuppressive drugs in heart and kidney organ transplants in animals. The data demonstrates that TNX-1500 showed activity in preventing organ rejection and was well tolerated in animals. Blockade of CD40L with TNX-1500 monotherapy consistently prevented pathologic alloimmunity in animal models of cardiac and kidney allograft model without evidence of clinical thrombosis.

In January 2021, the World Intellectual Property Organization published a patent application filed under the Patent Cooperation Treaty covering TNX-1500, a humanized mAb directed against CD40-ligand, which is also known as CD154. The patent application is titled “Anti-CD154 Antibodies and Uses Thereof” and published under International Publication No. WO 2021/001458 A1. The application entered national phase in December 2021. The patent applications include claims related to proprietary anti-human CD40-ligand mAbs that were engineered to have modified effector function, including TNX-1500, which have reduced potential for Fc binding to FcγRII. The patent applications also claim uses of TNX-1500 for preventing and treating conditions, such as organ transplant rejection and autoimmune disorders. If claims are granted, a patent issuing from a national stage of this application could potentially provide U.S. patent coverage for the TNX-1500 composition of matter through 2040 excluding possible patent term extensions or patent term adjustments. We also have filed a PCT patent application, PCT/US2022/011404, in January 2022, entitled “Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies.” It claims methods of inducing immune tolerance in transplant recipients using anti-CD154 antibodies having modified effector functions.

Remicade® and Simponi® are trademarks of Janssen; Humira® is a trademark of AbbVie Inc.; Cimzia® is a trademark of UCB S. A.; Enbrel®, Prolia® and Xgeva® are trademarks of Amgen Inc.

TNX-1700 — Gastric and Colorectal Cancers

TNX-1700 is a recombinant Trefoil ~~Family~~ Factor Family 2 ~~(hTFF2-HSA)~~fused ~~fusion protein in development~~ to ~~treat~~human ~~gastric~~serum ~~and~~albumin ~~colorectal~~(“hTFF2-HSA") ~~cancers. We have~~ licensed ~~rights~~ from The Trustees of Columbia University in the City of New York toin ~~develop~~development ~~a potential product, TNX-1700,~~ for the treatment of gastric and colorectal cancers. The licensed patents are ~~directed~~ directed to TFF2 compositions and methods of treatment., ~~The licensed patents~~ U.S. Patent No. 10,124,037 and U.S. Patent No. 11,167,010. The licensed patents provide TNX-1700 with US market exclusivity until April 2033, subject to any patent term extensions. On August 27, 2020, we ~~filed~~ filed International Patent Application No. PCT/IB2020/000699 entitled “Modified TFF2 Polypeptides.” The PCT application is now nationalized in 12 countries.

22In preclinical studies, we have shown efficacy of TNX-1700 in combination with anti-PD-1 in tumor reduction, metastasis and increase in survival in various models of gastric and colorectal cancer. The mechanism of action is to suppress immunosuppressive neutrophils and activate anti-cancer CD8+ T cells, which is distinct from checkpoint inhibitors. There is potential synergy with anti-PD-1 or anti-PD-L1 mAbs.

Preclinical data has shown that mTFF2-CTP augmented the efficacy of mAb anti-PD-1 therapy. Anti-PD-1 in combination with mTFF2-CTP showed greater anti-tumor activity in PD-L1-overexpressing mice. The mechanism of action is to suppress myeloid-derived suppressor cells and activate anti-cancer CD8+ T cells, which is different from checkpoint inhibitors. There is potential synergy with anti-PD-1 or anti-PD-L1 mAbs.

TNX-801 –Smallpox and Mpox Vaccine

TNX-801 is a novel potential smallpox- and mpox-preventing vaccine based on a synthetic version of live horsepox virus, grown in cell culture. Though it shares structural characteristics with vaccinia-based vaccines, TNX-801 has unique properties that we believe indicate potential safety advantages over existing live replicating vaccinia virus vaccines, which have been associated with adverse side effects such as myopericarditis in some individuals. Emergent BioSolutions’ ACAM2000® is the only replicating vaccinia virus vaccine currently approved by the FDA to protect against smallpox and mpox. We believe replicating virus vaccines have potential efficacy advantages over non-replicating vaccines, relating to the stimulation of cell mediated immunity. Bavarian Nordic’s Jynneos®, the only non-replicating virus vaccine, is currently approved by the FDA to protect against smallpox and mpox. Jynneos® requires two-doses, with an efficacy of approximately 35% after one dose. During the most recent mpox outbreak in the United States, dropout between doses was 24%. We believe TNX-801 has the potential to have improved tolerability relative to replicating vaccinia vaccines and the potential to have improved efficacy relative to non-replicating vaccinia vaccines. ~~We also believe that TNX-801 would require only one dose.~~

Smallpox was eradicated by a World Health Organization program that vaccinated individuals with live replicating vaccinia vaccines wherever smallpox appeared. In the 1970s, vaccination of civilians to protect against smallpox was discontinued in the U.S.; however, smallpox remains a material threat to national security and a proportion of military personnel, including members of the Global Response Force, continue to be vaccinated. The Bipartisan Commission on Biodefense (2024) noted that “Smallpox and other orthopoxviruses pose significant threats to the United States and the world due to their potential for weaponization, accidental release, and vulnerability of populations who stopped routinely vaccinating against smallpox in the 1970s~~” (Bipartisan Commission on Biodefense).~~

We are developing TNX-801 as a potential smallpox- and mpox-preventing vaccine for the U.S. strategic national stockpile and for potential widespread immunization in the event of malicious reintroduction of variola, the virus that causes smallpox.

Mpox has become endemic in the U.S. since it spread in the U.S. and other countries outside of Africa, mostly in populations of gay men. In August 2024, the WHO determined that the upsurge of mpox in a growing number of countries in Africa constitutes a public health emergency of international concern (“PHEIC”), the second such declaration in the past two years in response to transmission of the virus. Mpox cases of the new clade Ib mpox have since also been detected in multiple countries outside of Africa, including the U.S.. Animals vaccinated with TNX-801 were protected from mpox in studies reported in the first ~~quarter~~ quarter of 2020. These data were published in the peer-reviewed journal Vaccines in 2023. Although PHEIC designation has been lifted by WHO, mpox continues spread in Africa and mutations of the virus are considered by public health experts to be an ongoing threat to be monitored for new epidemic spread.

In October ~~November 2024~~2025, ~~Tonix~~at ~~announced that it has entered into a sponsored research agreement with~~ the ~~Kenya~~World ~~Medical~~Vaccine ~~Research~~Congress ~~Institute~~in ~~(KEMRI) to design~~Amsterdam, ~~plan~~we ~~and~~presented ~~seek~~data ~~regulatory~~showing ~~approval~~TNX-801, ~~for~~regardless aof ~~Phase~~route 1of ~~clinical~~administration ~~study in Kenya to test the safety~~(i.e., ~~tolerability~~intradermal, ~~and~~subcutaneous ~~immunogenicity~~or ofintramuscular) ~~TNX-801~~provided as100% aprotection ~~vaccine~~against tovaccinia ~~prevent~~virus ~~mpox~~ and ~~smallpox.~~monkeypox ~~Tonix~~virus ~~will~~challenge bein terms ~~the~~of ~~sponsor~~both mortality and ~~KEMRI~~clinical ~~will~~disease ~~lead~~(lesions) ~~the~~in ~~execution~~a ofhighly ~~the~~sensitive ~~proposed~~rabbitpox ~~clinical trial~~model.

In September 2024, at the DoD’s MHSRS conference and in October 2024 at the World Vaccine Congress in Barcelona, Spain, Tonix presented new data on potential mpox vaccine, TNX-801, demonstrating tolerability and no evidence of spreading to blood or tissues, even at high doses, in immunocompromised animals. After a single-dose vaccination, TNX-801 prevented clinical disease and lesions, and also decreased shedding in the mouth and lungs of animals after a lethal challenge with clade Ia monkeypox. These findings are consistent with TNX-801 inducing mucosal immunity and suggest TNX-801 has the ability to block forward transmission. In September 2024, the Company also announced that the WHO’s preferred TPP aligns with the characteristics of TNX-801. Key elements of the WHO draft TPP include single-dose, durable protection, administration without special equipment, and stability at ambient temperature. Other potential beneficial characteristics include the ability to limit forward transmission, use in case-contact vaccination strategies and suitability for use in immunocompromised individuals. 18

23In September 2024, at the DoD’s MHSRS conference and in October 2024 at the World Vaccine Congress in Barcelona, Spain, we presented new data on potential mpox vaccine, TNX-801, demonstrating tolerability and no evidence of spreading to blood or tissues, even at high doses, in immunocompromised animals. After a single-dose vaccination, TNX-801 prevented clinical disease and lesions, and also decreased shedding in the mouth and lungs of animals after a lethal challenge with clade Ia monkeypox. These findings are consistent with TNX-801 inducing mucosal immunity and suggest TNX-801 has the ability to block forward transmission. In September 2024, we also announced that the WHO’s preferred TPP aligns with the characteristics of TNX-801. Key elements of the WHO draft TPP include single-dose, durable protection, administration without special equipment, and stability at ambient temperature. Other potential beneficial characteristics include the ability to limit forward transmission, use in case-contact vaccination strategies and suitability for use in immunocompromised individuals.

In August 2024, Tonix and Bilthoven Biologicals, part of the world’s largest vaccine manufacturer the Cyrus Poonawalla Group, which includes the Serum Institute of India, announced a collaboration to advance TNX-801.

In October 2023, at the World Vaccine Congress - Europe, we reported that the TNX-801 vaccine was shown to be greater than 10 to 1,000-fold more minimally replicative than older vaccinia-based smallpox vaccines in both human primary cell lines and immunocompromised mice. Similar data was also published in the peer-reviewed journal mSphere which presented data demonstrating that TNX-801 is less virulent than 20th Century vaccinia vaccines in immune-compromised mice.

In August 2023 we received pre-IND meeting written responses from the FDA. Tonix believes the FDA feedback provides a path to agreement on the design of a Phase 1/2 study and the overall clinical development plan. The Phase 1/2 clinical trial will assess the safety, tolerability, and immunogenicity of TNX-801, following the submission and clearance of an IND. We are actively working to develop a vaccine meeting cGMP quality to support a clinical study.

In January 2020 at the American Society of Microbiology Biothreats conference, we reported the results of experiments on TNX-801 that were performed in collaboration with Southern Research, that showed TNX-801 vaccinated macaques were protected against monkeypox challenge. The TNX-801 vaccinated macaques showed no overt clinical signs after monkeypox challenge. Furthermore, eight of eight animals vaccinated with two different doses of TNX-801 showed no lesions after monkeypox challenge. These results were published in the peer-reviewed journal Viruses in 2023.

We hold a U.S. Patent for TNX-801 smallpox and mpox vaccine and Recombinant Pox Virus (RPV) platform technology. This patent is expected to provide Tonix with U.S. market exclusivity until 2037, excluding any possible patent term extensions or patent term adjustments. In addition, we expect that TNX-801 will be eligible for 12 years of non-patent-based exclusivity under the Patient Protection and Affordable Care Act, or PPACA.

TNX-801 also serves as the live virus vaccine platform for other infectious diseases for which subsequent products will be designed by expressing other viral antigens in the horsepox vector. ~~The~~Our ~~company’s~~ Good Manufacturing Practice (GMP)-capable advanced manufacturing facility in Dartmouth, MA was purpose-built to manufacture live virus vaccines, including TNX-801. ~~and~~The ~~the~~ GMP suites ~~are~~have ~~ready~~been todecommissioned and may be reactivated the earlier of 2027 or in case of a national or international emergency.

TNX-1800 – COVID-19 Vaccine

TNX-1800 is a minimally replicative, live virus vaccine based on our RPV platform that expresses the SARS-CoV-2 spike protein from the ancestral Wuhan strain. TNX-1800 is being further developed to rapidly address new variants as they emerge. The vaccine platform itself can carry a payload of genes. The vaccine protects against COVID-19 by eliciting a durable T cell, humoral and mucosal immune response. It is delivered in only one dose. In November 2023, Tonix announced that the NIAID, a part of the NIH, will conduct a Phase 1 clinical trial with TNX-1800 as part of the Project NextGen Covid-19 Vaccine initiative. This NIAID/NIH program is funded to take selected NextGen vaccine candidates into Phase 1 and Phase 2 trials. Because of extensive reviews of NIH programs, the future of this program is uncertain.

The COVID-19 vaccines that are approved for use in the U.S. have provided significant health benefits to the vaccinated population; however, they have shown limitations in the durability of protection conferred and in their limited ability to block the spread of infection (forward transmission). Live virus vaccines that protect against other viral diseases by eliciting T cell responses have shown durability of protection that lasts years to decades and some live virus vaccines have significantly inhibited forward transmission (e.g. smallpox). The TNX-1800 vaccine development plan is wholly consistent with priority vaccine attributes advanced by the White House Office of Science and Technology Policy’s Pandemic Preparedness Plan from September 2021, the National Biodefense Science Board report from August 2023, and the BARDA Strategic Plan 2022-2026. Tonix believes its RPV platform can address a wide variety of disease targets of public health interest.

The results of an animal study data showing the protective effect of TNX-1800 vaccine was published in the peer-reviewed journal Vaccines in 2023 and show that TNX-1800 induces complete protection against SARS-CoV-2 infection as well as evidence that indicates an impact on spread of infection. These data also confirm that “take” is a biomarker of protection of upper and lower airways from SARS-CoV-2 challenge, and a biomarker of immunological response to TNX-1800’s cargo COVID-19 antigen, which is the CoV-2 spike protein. Tonix has also began undertaking studies to show attenuation of the RPV platform itself in order to evaluate the potential use of the live vaccine platform in the immunocompromised host by the use of mouse model system. These data (detailed below) demonstrate that the RPV vaccine platform that is used for TNX-1800 is >10- to 1,000-fold more minimally replicative than older VACV-based smallpox vaccines in human primary cell lines and immunocompromised mice.

We received pre-IND meeting written responses from the FDA in 2021 regarding our investigational plan to establish the safety and effectiveness evidence in support of the licensure of TNX-1800. We believe that the FDA feedback provides a clear pathway forward towards utilizing its underlying RPV platform for a COVID-19 vaccine.

We announced the issuance of U.S. Patent for TNX-801 smallpox and mpox vaccine and RPV platform technology. This patent is expected to provide Tonix with U.S. market exclusivity until 2037, excluding any possible patent term extensions or patent term adjustments, and also expect 12 years of non-patent-based exclusivity under PPACA.

At the World Vaccine Congress in October 2023, Tonix presented its positive, published non-human primate data for the TNX-1800 (spike from Wuhan strain) from animal challenge studies using live SARS-CoV- 2. In this study TNX-1800 vaccinated, SARS-CoV-2 challenged animals had undetectable SARS-CoV-2 in the upper airways, which we believe relates to potential inhibition of forward transmission of this respiratory pathogen. Further, as an expected additional outcome, all 16 animals vaccinated with either dose of TNX-1800 or the control TNX-801 manifested a “take”, or cutaneous response, signaling that the horsepox vector elicits a strong T cell immune response. These results support the expectation that TNX-1800 at the low dose of 1 x 106 PFU is an appropriate dose for a one-dose vaccine in humans. These data were published in the peer-reviewed journal Vaccines in 2023.

Additional studies have been undertaken to show attenuation of the RPV platform alone (TNX-801) in order to evaluate the potential use of this live vaccine in the immunocompromised host. These data demonstrate that the RPV platform used with TNX-1800 is >10- to 1,000-fold more minimally replicative than older VACV-based smallpox vaccines in human primary cell lines and immunocompromised mice.

TNX-4200 – Broad-Spectrum Antiviral

~~Tonix~~We isare developing CD45-targeted therapeutics (TNX-4200). In July 2024 Tonix was awarded a contract with a potential for up to $34 million over five years by the U.S. Department of Defense, Defense Threat Agency (DTRA). The objective of the contract is to develop small molecule broad-spectrum antiviral agents for the prevention or treatment of infections to improve the medical readiness of military personnel in biological threat environments.

~~Tonix’s~~ Our program will focus on optimization and development of its TNX-4200 program, to develop an orally available CD45 antagonist, with broad-spectrum efficacy against a range of viral families through preclinical evaluation. The program is expected to establish physicochemical properties, pharmacokinetics, and safety attributes to support an IND submission and to fund a first-in-human Phase 1 clinical study. ~~Tonix~~We ~~plans~~plan to leverage previous research on phosphatase inhibitors, specifically compounds that target CD45, to optimize lead compounds for therapeutic intervention of biothreat agents and provide the government with a complete and cost-effective solution for a broad-spectrum medical countermeasure. Tonix’s hypothesis is that partial inhibition of CD45 will provide optimal antiviral protection while requiring lower plasma drug concentrations, a lower dose, and a better safety profile.

25TNX-4900

TNX-~~2900~~4900 –is ~~Prader~~a highly selective S1R antagonist with demonstrated analgesic activity in multiple animal models of neuropathic pain. TNX-~~Willi~~4900 was ~~Syndrome~~created from a structure-based drug design program led by Dr. Youyi Peng and Dr. William Welsh at Rutgers University that produced a series of potent and selective triazole-based S1R antagonists. The compound binds the human Sigma-1 receptor with nanomolar affinity (~~PWS~~Ki = 7.5 nM), demonstrates > 100-fold selectivity over the Sigma-2 receptor, and exhibits high blood-brain barrier penetration and favorable absorption, distribution, metabolism and elimination (ADME) properties, including oral bioavailability of approximately 28%. TNX-4900 is in the pre-IND stages of development. In preclinical models of diabetic and chemotherapy-induced neuropathic pain, TNX-4900 produced significant and durable reductions in pain behaviors after both acute and chronic dosing without evidence of tolerance or motor impairment. Tonix plans to advance TNX-4900 through expanded pharmacokinetic, formulation, and safety studies to support IND-enabling development.

TNX-2900 is based on our patented intranasal potentiated oxytocin formulation, or TNX-1900, but being developed for PWS. Tonix licensed technology using oxytocin-based therapeutics for the treatment of PWS and non-organic failure to thrive disease from Inserm. The licensing agreement has been negotiated and signed by Inserm Transfert, the private subsidiary of Inserm, on behalf of Inserm, Aix-Marseille Université and Centre Hospitalier Universitaire of Toulouse. PWS is recognized as the most common genetic cause of life-threatening childhood obesity and affects males and females with equal frequency and all races and ethnicities. There is currently no approved treatment for either the suckling deficit in infants or the obesity and hyperphagia in older children associated with PWS. Since PWS is an orphan disease that occurs in approximately one in 15,000 births, TNX-2900 for PWS has been granted Orphan Drug Designation and Rare Pediatric Disease Designation by the FDA. Tonix completed a pre-IND meeting with the FDA in November 2022 to discuss the most efficient and appropriate investigational plan to establish the safety and effectiveness evidence to support the approval of TNX-2900, and Tonix has received IND clearance. 19

In 2022, Tonix entered into a research collaboration with Inserm involving in vitro and in vivo animal studies designed to validate and characterize the role of oxytocin in suckling and in the maturation of feeding behavior during infancy in order to support an intranasal therapeutic approach to restore a normal nutritive suckling. The studies will include mice that have been engineered to precisely recapitulate the genetic issue underlying PWS in humans.

The mechanisms involved in suckling activity required for normal feeding and the role of oxytocin system in this process will be investigated. The results of this work are expected to be useful in the clinical care of infants requiring support to achieve efficient suckling behavior. Intranasal oxytocin has previously been shown to improve suckling in newborn animals and suppress feeding behaviors in adult animal models.

Tonix’s Facilities Overview

The Research & Development Center (RDC)

We own the approximately 48,000 square foot RDC facility in Frederick, Maryland. The RDC facility is operational and focuses on our development of vaccines and antiviral drugs against ~~COVID-19, its variants, and other~~ infectious diseases. The RDC is the principal site for the research on TNX-4200, a broad-spectrum antiviral targeting CD45 funded by the ~~U.S.~~DTRA ~~Department of Defense, Defense Threat Agency~~ contract. The RDC also conducts research on CNS and immunology drugs. The RDC facility is biosafety level 2 (BSL-2) with BSL-3 components.

The Advanced Development Center (ADC)

The ADC located in the New Bedford business park in Dartmouth, Massachusetts is intended to accelerate development, clinical and commercial scale manufacturing of live-virus vaccines and biologics. ADC includes single-use bioreactors and purification suites with equipment for Good Manufacturing Practice (GMP) production of vaccines and biologics for clinical trials, including the capability of producing sterile vaccines in glass vials.

The ADC is an approximately 45,000 square foot BSL-2 facility which can employ up to 70 researchers, scientists, manufacturing, and technical support staff. This facility was decommissioned in May 2024, ~~but~~and is ~~Tonix~~ready ~~has~~to be reactivated on the ~~ability~~earlier toof ~~reactivate~~2027 itor ~~should~~in wethe ~~choose to~~case doof soa national or international emergency.

26 Commercialization

Following FDA approval, we initiated the commercial launch of TONMYA in 2025, our first internally developed and commercialized product. We have established a focused commercial infrastructure and team designed to support launch execution, drive prescriber awareness, and enable patient access, while maintaining compliance with applicable regulatory and industry standards.

We commercialize TONMYA through our sales organization, which includes an internal sales force, and a contracted salesforce, non-personal promotion, digital engagement, market access programs, patient support services, and distribution through national wholesalers and specialty distributors. We are focused on obtaining payer coverage, building physician awareness, and driving adoption primarily in practices that have a history of diagnosing and treating fibromyalgia, which includes rheumatology, primary care, pain management and neurology practices.

We have contracted for two commercial supply sources of TONMYA in the U.S., one of which is Almac Pharma Services, a member of the privately owned Almac Group.

We have managed the continued commercial operations for Zembrace Symtouch and Tosymra, following the acquisition of these products in 2023.

Marketing, Sales and Distribution

Marketing activity for TONMYA, Zembrace Symtouch and Tosymra in the United States is conducted by our wholly-owned subsidiary, Tonix Medicines, Inc. We focus our sales and marketing efforts on physicians in private practice and in public treatment systems. We employ standard pharmaceutical marketing practices to promote our products, encompassing advertisements, professional symposia, sales initiatives, and educational outreach aimed at physicians, nurses, social workers, counselors, and other stakeholders involved in treating fibromyalgia and acute migraine in adults. We have established contracts with third-party vendors to handle logistics, offer customer services, and manage other related aspects for our products. These services include managing product-specific websites, conducting ~~insurance~~ insurance research, processing orders, and handling delivery and fulfillment services. TONMYA, Zembrace Symtouch and Tosymra are primarily sold to pharmaceutical wholesalers, pharmacies, and specialty distributors. We ~~intend~~have toimplemented ~~implement~~ patient access programs and expand distribution channels in our marketing efforts for our fibromyalgia and migraine drugs.

In 2024, Tonix engaged EVERSANA to support the launch strategy and commercial planning of TNX-102 SL for the management of fibromyalgia. Specifically, EVERSANA worked with Tonix to assess the fibromyalgia landscape and help plan an efficient go-to-market strategy. 20

In 2024, Tonix ~~hired~~engaged aEVERSANA ~~new head of Commercial Operations as well as Vice Presidents~~ to ~~run~~support ~~Medical~~the ~~Affairs~~launch strategy and ~~Marketing,~~commercial ~~each~~planning ~~with decades~~ of ~~experience~~TONMYA ~~successfully~~for ~~launching~~the ~~and~~treatment of ~~commercializing new CNS products~~fibromyalgia. ~~In January 2025~~Specifically, ~~Tonix~~EVERSANA ~~announced~~also ~~the~~worked ~~appointment~~with ofTonix ~~a vice president~~ to ~~oversee~~assess ~~Market~~the ~~Access.~~fibromyalgia Inlandscape ~~2025, we will continue to build out our commercial team~~ and ~~capabilities~~help asplan wean ~~look~~efficient ~~forward~~ go-to ~~a targeted launch of TNX~~-~~102~~market ~~SL in the fourth quarter of 2025, contingent on FDA approval~~strategy.

Our commercialization strategy for TONMYA is centered on a cost-efficient, targeted sales and marketing approach focused on the top prescribing healthcare providers who treat patients with fibromyalgia, including primary care physicians and relevant specialists. Our field-based promotion is conducted through a combination of internal commercial personnel and contracted sales representatives. As of December 31, 2025, our commercial organization included approximately 90 field sales representatives, inclusive of internal and contracted resources, supported by sales leadership, training, and operations functions.

In addition to field-based promotion, we utilize non-personal promotion and digital marketing initiatives to support disease awareness, product education, and appropriate utilization. These efforts are intended to complement in-person engagement and expand reach within our target prescriber universe. We have 11 employees supporting sales administration and marketing initiatives; customer service requests and top-tier headache specialists. We utilize third party vendors to support trade, managed markets, marketing initiatives, and promotional compliance programs.

TONMYA is distributed in the United States through national pharmaceutical wholesalers and specialty distributors pursuant to customary commercial arrangements. Tonix has contracted with its existing wholesalers and specialty pharmacies for the distribution of TONMYA. We utilize third-party logistics providers to support product warehousing, order fulfillment, and distribution activities. Our distribution and supply chain operations are structured to comply with applicable requirements, including those under the Drug Supply Chain Security Act (DSCSA). Product returns are managed in accordance with industry-standard practices.

Market Access and Patient Support

We have implemented a market access strategy intended to support broad and appropriate patient access to TONMYA across key payer segments, including commercial plans and government programs. Our market access efforts include engagement with payers and pharmacy benefit managers, formulary review processes, and contracting activities customary for prescription pharmaceutical products.

We also offer patient support services designed to assist with benefits verification, prior authorization support, and access to available patient assistance programs. These services are administered through third-party vendors and are intended to facilitate appropriate initiation and continuation of therapy, consistent with applicable laws and regulations.

Commercial Compliance and Oversight

We maintain policies, procedures, and controls designed to support compliant commercial operations, including a promotional review committee (PRC) process for review and approval of promotional and non-promotional materials, field force compliance training, and pharmacovigilance and adverse event reporting procedures. These activities are intended to support compliant engagement with healthcare professionals, patients, and other stakeholders as we execute our commercial strategy.

Competition

Our sector faces intense competition and experiences rapid, substantial technological advancements both domestically and internationally. Our potential competitors encompass major pharmaceutical and biotechnology firms, specialty pharmaceutical and generic drug manufacturers, academic institutions, government agencies, and research organizations. We consider efficacy, safety, tolerability, reliability, pricing, and reimbursement levels as crucial competitive factors influencing the development and commercial success of our product candidates. Numerous potential competitors, including some of the organizations listed below, possess considerably larger financial, technical, and human resources, as well as extensive experience in discovering and developing product candidates, securing FDA and other regulatory approvals, and commercializing those products, far surpassing our own capabilities. Hence, our competitors might achieve greater success in securing FDA approval for drugs and gaining widespread market acceptance compared to us. The drugs offered by our competitors may prove to be more effective or better marketed and sold than any product we bring to market, potentially rendering our product candidates obsolete or non-competitive before we can recoup the expenses incurred in their development and commercialization. We expect to encounter heightened competition as the market sees the introduction of new drugs and the emergence of advanced technologies. Additionally, the evolution of novel treatment approaches for the conditions we are focusing on may potentially diminish the competitiveness or relevance of our drugs. Below, we provide an overview of the competitive landscape for the indications where Tonix has product candidates either in or nearing the clinical stages of development.

~~Migraine~~ 21

Zembrace Symtouch and Tosymra are indicated for the treatment of acute migraine and compete with generic versions of sumatriptan. Zembrace is an autoinjector formulation of sumatriptan and competes with generic subcutaneous products. Tosymra is an intranasal formulation of sumatriptan and competes with generic intranasal products. Zembrace and Tosymra also compete with the new molecular entities including oral migraine therapies such as Nurtec® (Rimegepant) from Pfizer Inc. and Ubrelvy® (Ubrogepant) and QULIPTA® (atogepant) from AbbVie Inc. and intranasal migraine therapies such as Zavzpret™ (vazegepant) by Pfizer, Inc. Most recently, Axsome Therapeutics announced FDA approval of SYMBRAVO® (meloxicam and rizatriptan) for the acute treatment of migraine with or without aura in adults. We also note that the PDUFA goal date for Shin Nippon Biomedical Laboratories, Ltd and Satsuma Pharmaceuticals is April 30, 2025 for their intranasal asset STS101 (dihydroergotamine) for the treatment of migraine headaches.

Fibromyalgia

WeAs ~~are~~of ~~currently~~2026, ~~awaiting~~the anU.S. fibromyalgia therapeutic landscape consists of four FDA-approved ~~decision~~treatments.. onThe ~~marketing~~first ~~authorization~~three ~~for~~products - pregabalin (Lyrica ®), duloxetine (Cymbalta a®), and milnacipran (Savella ~~TNX~~a®) -~~102~~ SLreceived ~~for~~FDA approval between 2007 and 2009 and have represented the ~~management~~standard of ~~fibromyalgia.~~care ~~There~~for ~~are~~more 3than ~~products~~a decade. In August 2025, FDA approved ~~for~~TONMYA, the ~~treatment~~first ofnew fibromyalgia ~~which~~treatment ~~include~~in ~~Lyrica® (pregabalin),~~more ~~developed~~than by15 ~~Pfizer,~~years ~~Inc.,~~and ~~Cymbalta®~~the ~~(duloxetine),~~first ~~developed~~approved bytherapy ~~Eli~~aimed ~~Lilly~~at ~~and~~improving ~~Company~~non-restorative sleep, ~~and~~a ~~Savella®~~core ~~(milnacipran) marketed~~contributor byto ~~AbbVie.~~fibromyalgia ~~Pregabalin~~pain and ~~duloxetine~~fatigue. ~~are~~The ~~available~~U.S. asfibromyalgia ~~generics~~market has historically been characterized by limited innovation and treatment dissatisfaction, ~~while~~with ~~Savella~~many ispatients ~~still~~cycling onthrough ~~patent.~~therapies ~~There~~or ~~has~~relying ~~not~~on ~~been~~off-label aanalgesics ~~new~~due ~~product~~to incomplete ~~approved~~symptom ~~for~~control. ~~this~~The ~~indication~~approval inof 15TONMYA ~~years~~introduces a differentiated mechanism targeting nonrestorative sleep.

~~Tonix~~We actively ismonitor ~~aware of~~ multiple companies ~~actively~~advancing ~~developing~~investigational ~~treatments~~ therapies for fibromyalgia. In the U.S., Axsome Therapeutics, Inc. initiated ~~expects~~their toPhase ~~submit~~3 antrial ~~NDA~~of ~~for~~ AXS-14 (esreboxetine) for the management of fibromyalgia ~~to the FDA for AXS-14~~ in Q1January ~~2025~~2026. ~~Virios~~ Dogwood Therapeutics, Inc. ~~announced~~(formerly ~~the~~Virios ~~initiation~~Therapeutics, ~~of a Phase 3 trial in the U~~Inc.S.) ~~for~~continues ~~IMC-1 for~~ the ~~treatment~~ development of ~~fibromyalgia.~~ IMC-1, is a fixed -dose combination of famciclovir + celecoxib. Outside the U.S., isOno aPharmaceutical ~~505(b)(2)~~is ~~and~~advancing ~~has~~ONO-1110 ~~been~~as ~~granted~~an ~~Fast~~oral ~~Track~~medication ~~Designation by~~designed ~~the~~for ~~FDA~~endocannabinoid regulation. ~~Tonix~~The drug is ~~also~~being ~~focused~~developed onin ~~developments~~Japan for ~~fibromyalgia~~several ~~outside~~indications, ofincluding ~~the~~fibromyalgia, ~~U.S.~~postherpetic neuralgia, and major ~~keeps~~depressive ~~abreast~~disorder. ~~of the progress made by Australian company~~ Tryptamine Therapeutics Ltd. ~~who~~reported ~~announced~~ positive ~~data from a~~ Phase IIa ~~clinical~~data ~~trial~~for of TRP-8802 ~~for~~in fibromyalgia ~~which was presented in an abstract~~ at the ~~International~~ ~~Association for the Study of Pain (~~2024 IASP) ~~2024 World Congress on August 9, 2024~~meeting.

~~Long~~Migraine ~~COVID (Post-Acute Sequelae of SARS-CoV-2 Infection or PASC)~~

AsZembrace SymTouch ofand ~~now,~~Tosymra ~~there~~continue ~~are~~to noserve ~~specific drugs approved by~~ the ~~FDA~~acute ~~solely~~migraine ~~for the~~market ~~treatment of Long COVID (formerly known~~ as ~~Post-Acute~~branded ~~Sequelae~~formulations of ~~SARS-CoV-2 Infection (PASC)). Tonix is aware of several companies developing therapeutics for the treatment of Long COVID including~~sumatriptan, ~~but~~competing ~~not~~directly ~~limited to, Direct Biologics, LLC (Phase III for DB-001 was~~with ~~completed~~generic insubcutaneous ~~the fourth quarter of 2024~~ and ~~American~~intranasal ~~CryoStem Corporation~~products. ~~Other~~Beyond ~~developments~~generic ~~include Organicell Regenerative Medicine~~pressure, ~~Inc.~~ isboth ~~conducting~~brands anow ~~Phase~~operate 2within ~~for~~an ~~Zofin as~~increasingly ~~a potential therapeutic for Long COVID. PaxMedica, Inc. is developing PAX-101 for the treatment~~competitive oflandscape ~~Long~~shaped ~~COVID~~by ~~and currently conducting a Phase1b in South Africa. In October 2024, Resolve Therapeutics, LLC, announced~~ the ~~results~~growth ~~from its Phase II Long COVID study~~ of ~~RSLV~~next-~~132.~~generation ~~Furthermore,~~acute ~~GeNeuro announced the data from Phase II GNC-501 clinical trial in patients suffering from Long COVID~~therapies, ~~testing~~including ~~temelimab~~oral ~~against~~CGRP ~~placebo.~~antagonists ~~Finally,~~such inas ~~June 2024, Berlin Cures Holding AG announced that it is preparing~~Pfizer’s ~~for~~Nurtec® ~~a Phase~~ODT ~~III~~(rimegepant) ~~study~~and inAbbVie’s ~~Long~~Ubrelvy® ~~COVID~~(ubrogepant) and ~~Statera~~Qulipta® ~~BioPharma~~(atogepant), ~~Inc.~~as iswell ~~comparing STAT-205~~as ~~with~~intranasal CGRP ~~placebo~~options ~~for~~like ~~reducing~~Pfizer’s ~~fatigue~~Zavzpret™ ~~in Long COVID~~(zavegepant).

The competitive environment expanded further in 2025 with the FDA approval of Axsome Therapeutic Inc.’s Symbravo® (meloxicam and rizatriptan). Satsuma Pharmaceuticals, Inc. received FDA approval for Atzumi, a nasal powder formulation of DHE (dihydroergotamine) for acute treatment of migraine.

Meanwhile, broader migraine development pipelines including but not limited to assets such as PUR-3100, an orally inhaled dry-powder formulation of dihydroergotamine (DHE) developed by Pulmatrix, Inc., signal ongoing innovation and expected market expansion through 2026 as companies advance differentiated mechanisms and delivery formats.

Major Depressive Disorder

Many antidepressant medications are beyond their patent life and are generally produced by generic drug companies, including several compounds in the tricyclic class (e.g., amitriptyline), the serotonin-selective reuptake inhibitor class (e.g., fluoxetine, paroxetine and sertraline), the serotonin-norepinephrine reuptake inhibitor class (e.g., venlafaxine, duloxetine), as well as the norepinephrine-dopamine reuptake inhibitor, bupropion. Tonix is aware of several companies developing novel prescription medicines for depression, including companies with late-stage (Phase 3) clinical-stage programs, including but not limited to: Johnson & Johnson, Inc., Luye Pharma Group, Ltd., Definium Therapeutics, Inc., and Vanda Pharmaceuticals, Inc.

Acute Stress Reaction/Acute Stress Disorder (ASR/ASD)

There are currently no approved drugs specifically for treating acute stress reaction (ASR) or for the prevention of ~~ASD~~acute orstress ~~PTSD~~disorder (ASD). InAs ~~October~~of ~~2024~~late 2025, ~~BioXcel~~BXCL501 ~~Therapeutics~~(dexmedetomidine ~~announced~~sublingual afilm) ~~Phase~~which ~~IIa~~is ~~efficacy~~the ~~and~~FDA-approved ~~safety~~drug ~~trial~~marketed ofas ~~BXCL501~~IGALMI® ~~in patients experiencing~~remains ~~ASD~~under ~~resulting~~investigation ~~from~~for ~~motor~~stress-related ~~vehicle~~indications ~~collisions~~but ~~to begin~~is innot ~~the~~approved ~~first~~for ~~half~~ASR, ofASD, ~~2025~~or PTSD. ~~BXCL501~~BioXcel isTherapeutics, anwith ~~orally dissolvable film formulation~~U.S. Department of ~~the~~Defense ~~α2A~~support, ~~adrenergic~~expects ~~receptor~~to ~~agonist~~begin ~~dexmedetomidine~~a ~~that~~Phase is2a ~~FDA~~trial ~~approved as IGALMI® for the acute treatment~~ of ~~agitation associated~~BXCL501 ~~with~~in ~~schizophrenia~~patients orexperiencing ~~bipolar~~ASD Ifollowing ormotor ~~II disorder in adults~~vehicle collisions.

~~Cocaine Intoxication~~ 22

~~There are no approved antidotes for the treatment of cocaine intoxication.~~Lyme Patients generally receive supportive care. We are not aware of any drugs in development for the treatment of cocaine intoxication. We are aware of companies that are targeting cocaine use disorder and we monitor their progress. Embera NeuroTherapeutics currently lists EMB-001 in Phase II development for the treatment of cocaine use disorder in its pipeline.Disease

28There are no approved drugs for Lyme disease prevention. We are aware of several companies currently developing Lyme Disease vaccines. Pfizer, in collaboration with Valneva, is developing VLA15, a multivalent recombinant protein subunit vaccine designed to prevent Lyme in the U.S. and Europe. The program has completed its Phase 3 VALOR trial vaccinations, with a data readout expected in the first half of 2026.

Moderna is advancing two mRNA-based vaccine candidates as part of its bacterial vaccine program (mRNA-1982 and mRNA-1975), which are in Phase I/II clinical trials.

Transplantation Rejection and Autoimmune Treatments with Anti-CD40-ligand Monoclonal Antibodies

We are aware of multiple companies advancing the development of biologics targeting the CD40L molecule. ~~including~~ Sanofi,’s ~~UCB, Eledon Pharmaceuticals, and Amgen~~Frexalimab ~~Inc.~~(SAR441344) ~~Eledon~~is ~~Pharmaceuticals~~in ~~revealed promising results from the~~ Phase ~~I/II~~III ~~trial~~development offor ~~tegoprubart,~~Multiple ~~aimed at preventing islet transplant rejection in individuals with type 1 diabetes~~Sclerosis. ~~The~~Frexalimab ~~trial~~is ~~showed~~also ~~that~~being ~~the~~advanced ~~first~~in ~~human~~clinical ~~cases~~trials offor ~~insulin independence were achieved using~~other anautoimmune ~~anti-CD40L monoclonal antibody therapy~~diseases, ~~without~~including ~~relying~~Systemic onLupus ~~tacrolimus,~~Erythematosus. ~~the~~Eledon ~~current~~Pharmaceuticals ~~standard~~is ~~treatment~~advancing tegoprubart for ~~preventing~~ organ transplant rejection. ~~Sanofi’s~~ ~~SAR441344~~The ~~(Frexalimab),~~company acompleted ~~second-generation~~its ~~anti-CD40L~~Phase ~~monoclonal~~II ~~antibody,~~(BESTOW) istrial ~~being tested~~ in ~~multiple~~2025 ~~sclerosis.~~and ~~In a~~plans ~~Phase~~to IImeet ~~trial involving participants~~ with ~~relapsing~~the ~~multiple~~FDA ~~sclerosis~~to ~~(NCT04879628),~~discuss ~~frexalimab~~Phase ~~demonstrated effectiveness in quickly~~III ~~reducing~~trial ~~the~~design ~~number~~and ofdata ~~new~~requirements ~~gadolinium-enhancing~~in ~~T1-lesions at week 12~~2026. Amgen Inc. is currently conducting a Phase III trial to test ~~Dazodalibep~~ dazodalibep for Sjogren’s Syndrome, ~~(NCT06104124)~~ with an estimated completion date for the ~~first half of 2026. H. Lundbeck is testing Lu AG22515 for Thyroid Eye Disease (TED) and plans to report results from the Phase Ib TED study in the~~ second half of 2026. In ~~2024, UCB and Biogen announced positive results from a Phase III trial testing Dapirolizumab Pegol for Systemic Lupus Erythematosus. In~~ November 2024, UCB and Biogen announced the initiation of their potentially confirmatory Phase III trial to test ~~Dapirolizumab~~ dapirolizumab Pegol for Systemic Lupus Erythematosus ~~(NCT06617325)~~. ~~These~~Biogen ~~are~~expects atopline ~~few~~data ~~key~~readouts ~~highlights that underscore the focus of major pharmaceutical companies~~ in ~~this~~late ~~area~~2027 ~~and~~or weearly monitor the activity of other companies in the process of developing antagonistic anti-CD40 mAbs, including Novartis, Boehringer Ingelheim GmbH, Kiniska Pharmaceuticals, Boston Immune Therapies, and NapaJen Pharma Inc2028.

These are a few key highlights that underscore the focus of major pharmaceutical companies in this area and we monitor the activity of other companies in the process of developing antagonistic anti-CD40 mAbs, including Novartis, Boehringer Ingelheim GmbH, Kiniska Pharmaceuticals, Boston Immune Therapies, and NapaJen Pharma Inc.

Prader Willi Syndrome

~~Somatropin,~~Vykat® ~~which~~(Diazoxide ~~targets~~Choline), ~~the~~developed ~~Growth~~by ~~Hormone~~Soleno ~~Receptor~~Therapeutics, is approved ~~in the U.S. and marketed by Pfizer Inc. and Novo Nordisk. Novartis AG markets Omnitrope® in Europe. There are no approved products~~ for the treatment of ~~hyperphagia~~Prader orWilli ~~over-eating~~Syndrome in (PWS). ~~Patients~~Tonix ~~generally~~is ~~receive~~aware ~~care~~of toseveral ~~best manage~~companies ~~individual symptom presentation. ACADIA Pharmaceuticals Inc.~~ currently ~~have ACP-101 (intranasal carbetocin) (acquired Levo Therapeutics~~ indeveloping ~~June~~treatments ~~2022)~~for ~~in a Phase 3~~PWS, ~~randomized,~~including ~~double-blind,~~Harmony ~~placebo-controlled,~~Biosciences ~~8-week clinical study to assess the efficacy, safety,~~ and ~~tolerability, of~~Aardvark ~~ACP-101 in PWS with long term follow-up~~Therapeutics. ~~Acadia~~Harmony ~~anticipates~~Biosciences ~~the~~is ~~enrollment~~advancing ofpitolisant ~~the final patient~~ in ~~by the fourth quarter of 2025, with~~ ~~top-line~~a ~~results~~Phase ~~expected~~III toclinical betrial ~~announced in the first half of 2026. Soleno is developing diazoxide chloride controlled release~~ (~~DCCR~~TEMPO) ~~which had positive results in a randomized withdrawal study of PWS~~. ~~The PDUFA goal date for a decision on marketing authorization is in March 2025.~~

Carmot Therapeutics Inc. announced that they plan to release Phase I single ascending dose (SAD)/MAD data for CT-PYY in 2025 for the treatment of PWS. Harmony Biosciences Holdings, Inc. received Orphan Drug Designation for their asset Wakix (pitolisant hydrochloride) for the treatment of PWS. Harmony Biosciences announced initial topline results from its Phase II proof-of-concept study in patients with PWS, which showed a signal on improvement in the primary outcome related to excessive daytime sleepiness in November 2022. At the end of 2024, Neuren Pharmaceuticals Limited announced the suspension of its Phase II open-label study of the safety, tolerability, and pharmacokinetics of oral NNZ-2591 in Prader-Willi syndrome (PWS-001) due to a revised development strategy.

Tonix is knowledgeable about several companies dedicated to developing a therapy for the treatment of PWS including, but not limited to, Aardvark Therapeutics, ConSynance Therapeutics, Lipidio Pharma, Helsinn, Inversago Pharma, Saniona, 9 Meters Biopharma, Neuracle Science, Harmony Biosciences Holding Inc., and Notitia Biotechnologies.

Gastric and Colorectal Cancer

~~TNX-1700 asset is a recombinant TFF2 (albumin fusion peptide) and has~~We ~~demonstrated~~are that by targeting myeloid derived suppressor cells (MDSCs) using TFF2-MSA fusion protein synergizes well with PD-1 blockade therapy in advanced and metastatic syngeneic mouse models of colorectal cancer. Tonix is aware of several companies that are focused on ~~MDSCs~~ todeveloping ~~treat~~treatments for Gastric and Colorectal Cancer., ~~Anbogen announced~~including abut ~~drug~~not limited ~~supply collaboration~~ to: ~~evaluate~~Johnson ~~the~~& ~~combination of Anbogen’s ABT-301~~Johnson, ~~with~~AbbVie ~~BeiGene’s tislelizumab, in patients with mismatch repair–proficient or microsatellite stable metastatic colorectal cancer (“mCRC”) in a global Phase II trial~~Inc. ~~Gilead Sciences and Arcus Biosciences announced new data from Cohort B of ARC-9~~, aAstraZeneca ~~Phase Ib/II study evaluating the safety and efficacy of etrumadenant~~PLC, aRoche ~~dual~~Holding ~~A2a/b adenosine receptor antagonist~~AG, ~~plus~~Novartis ~~anti-PD-1 monoclonal antibody zimberelimab~~AG, ~~FOLFOX~~Merck ~~chemotherapy~~& ~~and bevacizumab (EZFB) in third-line mCRC~~Co. ~~In 2023, TriSalus Life Sciences announced it plans to initiate a Phase II trial of SD-101 (Nelitolimod) for colorectal cancer~~Inc. ~~NextCure~~, Pfizer Inc. ~~have NC410 in the clinic~~, ~~for~~GSL ~~Colorectal~~plc, ~~Cancer.~~Bristol ~~Faron~~Myers ~~Pharmaceuticals~~Squibb ~~Oy have Bexmarilimab in the clinic for Colorectal Cancer. Merck & Co.~~Company, ~~Inc.~~BioNtech SE and ~~Agenus~~ ~~are~~Jazz ~~collaborating on MK-4830 for Colorectal Cancer~~Pharmaceuticals.

Smallpox / Mpox

~~BioNTech~~There SEare ismultiple ~~conducting~~approved avaccines ~~Phase~~globally ~~I/II~~for ~~study in~~ the ~~U.S.~~prevention ~~evaluating~~of ~~the~~smallpox ~~safety, tolerability, reactogenicity~~ and ~~immunogenicity of the investigational RNA-based multivalent vaccine candidate BNT166a for active immunization against~~ mpox. ~~The~~including ~~study~~Jynneos®, isdeveloped ~~expected~~by toBavarian ~~complete~~Nordic, inACAM2000®, ~~the~~developed ~~first~~by ~~quarter~~Emergent ofBioSolutions, ~~2026.~~and ~~In 2023~~LC16m8®, ~~Moderna~~developed ~~announced~~by itKM ~~has mRNA-1769 in preclinical development for the treatment of Mpox~~Biologics. ~~Moderna~~We isare ~~conducting~~aware ~~a P1/2 study~~ of ~~mpox vaccine in the U.K. Emergent BioSolutions, Inc. has enabled the enrolment~~several ofcompanies ~~the~~currently ~~first~~developing ~~patients for the MOSA, a pan~~next-~~African~~generation ~~randomized~~vaccines ~~platform~~for ~~adaptive~~smallpox ~~trial~~and ~~to test Tembexa to treat~~ mpox ~~at Mbandaka Hospital in Equateur Province~~, ~~Democratic~~including ~~Republic~~but ofnot ~~Congo. A~~limited ~~first~~to: ~~interim analysis is expected by the end of the first quarter of 2025. Other companies we monitor include GeoVax Labs~~Moderna, ~~Inc.,~~BioNTech ~~NanoViricides~~SE, ~~Inc.,~~GeoVax and ~~EpiVax, Inc~~NonoViricides.~~, Gylden Pharma Limited.~~

~~Covid-19~~ Cocaine Intoxication

There are ~~many~~no ~~vaccine~~approved ~~products~~antidotes ~~in development~~ for the treatment ~~or prevention~~ of ~~Covid-19~~cocaine ~~globally~~intoxication. ~~Approved~~Patients ~~products~~generally ~~include Pfizer-BioNTech’s~~receive ~~(BNT162b2),~~supportive ~~Moderna’s~~care. ~~(mRNA-1273)~~We ~~and Novavax’s (NVX-CoV2373) which~~ are ~~routinely~~not ~~updated~~aware toof ~~address~~any ~~new~~drugs ~~variants. CSL and Arcturus announced that the European Commission has granted marketing authorization for KOSTAIVE (ARCT-154), an mRNA COVID-19 vaccine, KOSTAIVE is currently marketed~~ in ~~Japan~~development ~~against COVID-19. Codagenix is developing CoviLiv™ as an intranasal vaccine candidate and in Phase 3~~ for ~~COVID-19. Other companies working in~~ the ~~area include:~~treatment ~~Vaxart Inc. which is developing a potentially orally administered vaccine based on the adenovirus serotype 5 (Ad-5) vector to express the spike protein~~ of ~~SARS-CoV-2;~~cocaine ~~CastleVax USA which is developing a potential nasally administered vaccine based on a Newcastle disease virus (NDV) vector to express the Spike protein of SARS-CoV-2~~intoxication.

Intellectual Property

We believe that we have an extensive patent portfolio and substantial know-how relating to TNX-102 SL, Zembrace®, Tosymra®, TNX-1300, TNX-1500, TNX-2900, TNX-1900, TNX-801, TNX-1800 and TNX-1700, and our other product candidates. Our patent portfolio, described more fully below, includes claims directed to various compositions and methods of use related to our product candidates. As of March 105, ~~2025~~ 2026, the patents we are either the owner of record of or own the contractual right to include 4245 issued U.S. patents and ~~432~~46 issued non-U.S. patents. We are actively pursuing an additional 2322 U.S. non-provisional patent applications, 34 international patent applications (PCT), and ~~244~~238 non-U.S./non-~~international~~PCT patent applications.

We strive to protect the proprietary technology that we believe is important to our business, including our proprietary technology platform, our product candidates, and our processes. We seek patent protection in the U.S. and internationally for our products, their methods of use and processes of manufacture, and any other technology to which we have rights, where available and when appropriate. We also rely on trade secrets that may be important to the development of our business.

Our success will depend on 1) the ability to obtain and maintain patent and other proprietary rights in commercially important technology, inventions and know-how related to our business, 2) the validity and enforceability of our patents, 3) the continued confidentiality of our trade secrets, and 4) our ability to operate without infringing the valid and enforceable patents and proprietary rights of third parties. We also rely on continuing technological innovation and in-licensing opportunities to develop and maintain our proprietary position.

We cannot be certain that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications we may own or license in the future, nor can we be certain that any of our existing patents or any patents we may own or license in the future will be useful in protecting our technology. For this and more comprehensive risks related to our intellectual property, please see “Risk Factors — Risks Relating to Our Intellectual Property.”

The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained. In most countries in which we file, the patent term is 20 years from the date of filing the first non-provisional priority application. In the United States, a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the PTO in granting a patent or may be shortened if a patent is terminally disclaimed over another patent.

The term of a U.S. patent that covers a drug approved by the FDA or methods of making or using that drug may also be eligible for patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process. The Drug Price Competition and Patent Term Restoration Act, also known as the Hatch-Waxman Act, is a federal law that encourages new drug research by restoring patent term lost to regulatory delays by permitting a patent term extension of up to five years beyond the statutory 20-year term of the patent for the approved product or its methods of manufacture or use if the active ingredient has not been previously approved in the U.S. The length of the patent term extension is related to the length of time the drug is under regulatory review. A patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only one patent applicable to an approved drug may be extended. Similar provisions are available in Europe and some other foreign jurisdictions to extend the term of a patent that covers an approved drug.

When possible, depending upon the length of clinical trials and other factors involved in the filing of an NDA, we expect to apply for patent term extensions for patents covering our product candidates and their methods of manufacture or use.

The patent portfolios for our proprietary technology platform and our most advanced product candidates as of ~~February~~March 105, ~~2025~~2026 are summarized below.

TNX-102 SL — Central Nervous System Conditions

Our patent portfolio for TNX-102 SL includes patents and patent applications directed to compositions of matter of CBP, formulations containing CBP, and methods for treating CNS conditions, such as TNX-102 SL for PTSD, for pain, fatigue and sleep disturbances in fibromyalgia, for treating or managing fibromyalgia (early onset response, favorable tolerability, or side effect profile), for alcohol abuse, for disordered sleep, for sexual dysfunction, for depression in fibromyalgia, for fatigue and disordered sleep (e.g., CAP rates), for post-acute sequelae of SARS-CoV-2 infection, for acute stress reaction/acute stress disorder, and for agitation in neurodegenerative conditions, e.g., AD.

Certain eutectic compositions were discovered by development partners and are termed the “Eutectic Technology.” The patent portfolio for CBP compositions (e.g., TNX-102 SL) relating to the Eutectic Technology includes patents and patent applications directed to eutectic compositions containing CBP, eutectic CBP formulations, methods for treating PTSD and other CNS conditions utilizing eutectic CBP compositions and formulations, and methods of manufacturing eutectic CBP compositions. The Eutectic Technology patent portfolio includes U.S. patents, such as U.S. Patent No. 9,636,408, U.S. Patent No. 9,956,188, U.S. Patent No. 10,117,936, U.S. Patent No. 10,357,465, U.S. Patent No. 10,864,175, U.S. Patent No. 11,026,898, and U.S. Patent No. 11,839,594. These U.S. patents and counterpart non-U.S. patents, and any U.S. and non-U.S. patents that issue in the future from this portfolio would expire in 2034 or 2035, excluding any patent term adjustments or extensions.

The unique pharmacokinetic profile of TNX-102 SL, or the PK Technology, was discovered by Tonix and its development partners. The patent portfolio for TNX-102 SL relating to the PK Technology includes patent applications directed to compositions of matter of CBP, formulations containing CBP, methods for treating PTSD, agitation in neurodegenerative conditions, and other CNS conditions utilizing these compositions and formulations. The PK Technology patent portfolio includes U.S. Patent Application No. 1319/~~918~~409,~~692~~704. If U.S. and non-U.S. patents claiming priority from those applications issue, those patents would expire in 2033, excluding any patent term adjustments or extensions.

31 24

On May 2, 2017, U.S. Patent No. 9,636,408 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The patent claims recite pharmaceutical compositions comprising the eutectic. The patent claims also recite methods of manufacturing the eutectic.

On September 13, 2017, European patent 2,501,234, entitled “Methods and Compositions for Treating Symptoms Associated with PTSD Using Cyclobenzaprine”, issued. This patent recites the use of CBP for the treatment of PTSD. On January 11, 2024, the European Patent Office Technical Board of Appeal reversed the October 2019 decision of the Opposition Division of the European Patent Office maintaining the patent in unamended form and held the patent to be invalid. No appeal may be taken from that decision.

On December 15, 2017, Japanese Patent No. 6259452, entitled “Compositions and Methods for Transmucosal Absorption,” issued. These claims relate to the pharmacokinetic profile of TNX-102 SL.

On August 3, 2022, European Patent No. 2861223, entitled “Compositions and Methods for Transmucosal Absorption,” issued. These claims relate to the pharmacokinetic profile of TNX-102 SL.

On March 20, 2018, U.S. Patent No. 9,918,948 entitled “Methods and Compositions for Treating Symptoms Associated with PTSD Using Cyclobenzaprine,” issued. The claims recite a method of using TNX-102 SL’s active ingredient cyclobenzaprine to treat PTSD and provides US market exclusivity until 2030, excluding any patent term extensions.

On March 23, 2018, Japanese Patent No. 6310542 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The claims recite pharmaceutical compositions comprising the eutectics and methods of manufacturing these eutectic formulations.

On May 1, 2018, U.S. Patent No. 9,956,188, entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The claims recite a eutectic of cyclobenzaprine hydrochloride and mannitol and methods of making those eutectics.

On November 6, 2018, U.S. Patent No. 10,117,936, entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The claims recite pharmaceutical compositions of eutectics of cyclobenzaprine hydrochloride and mannitol and methods of making those compositions.

On April 16, 2019, Chinese Patent No. ZL 201480024011.1 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The claims recite pharmaceutical compositions comprising eutectics of cyclobenzaprine hydrochloride and mannitol and methods of making those compositions.

On August 4, 2023, Chinese Patent No. ZL201910263541.6, entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride,” issued. The claims recite a eutectics of cyclobenzaprine hydrochloride and beta-mannitol and methods of making those eutectics.

On July 23, 2019, U.S. Patent No. 10,357,465 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride”, issued. The claims recite a eutectic of cyclobenzaprine hydrochloride and mannitol and methods of making those eutectics.

On December 11, 2019, European patent 2968992, entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride”, issued. This patent recites pharmaceutical compositions comprising a eutectic of mannitol and Cyclobenzaprine HCl and methods of making the same. In response to an opposition filed in September 2020 by Hexal AG, the European Patent Office’s Opposition Division upheld the patent in unamended form after the January 2022 oral proceedings. Hexal AG did not appeal that decision.

On December 25, 2019, European patent 2,683,245, entitled “Methods and Compositions for Treating Depression Using Cyclobenzaprine”, issued. The claims recite the use of CBP for the treatment of depression in a FM patient. This patent provides TNX-102 SL with European market exclusivity until March 2032 and may be extended based on the timing of the European marketing authorization of TNX-102 SL for depression in a FM patient. In September 2020, Hexal AG filed an opposition against this patent. The European Patent Office’s Opposition Division upheld the patent claims in unamended form after the February 2022 oral proceedings. Hexal AG did not appeal that decision.

On June 4, 2024, U.S. Patent No. 11,998,516, entitled “Methods and Compositions for Treating Depression Using Cyclobenzaprine,” issued. The claims recite methods for treating major depressive disorder in a fibromyalgia patient using a composition comprising cyclobenzaprine or its salts.

On December 15, 2020, U.S. Patent No. 10,864,175 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The claims recite a eutectic comprising cyclobenzaprine hydrochloride and beta-mannitol.

On December 12, 2023, U.S. Patent No. 11,839,594 entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The claims recite a method of manufacturing a eutectic comprising cyclobenzaprine hydrochloride and beta-mannitol comprising mixing or milling.

On February 14, 2024, European Patent No. 3,650,081, entitled “Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride”, issued. The claims recite a eutectic of mannitol and cyclobenzaprine hydrochloride and methods of manufacturing a eutectic.

On April 8, 2021, U.S. non-provisional Patent Application No. 17/226,058 and International Patent Application No. PCT/US2021/026492, entitled “Cyclobenzaprine Treatment for Sexual Dysfunction” were filed. The PCT application is now nationalized in Australia, Canada, China, European Patent Office, Japan, and Hong Kong. On October 5, 2022, International Patent Application No. PCT/US2022/045791, entitled “Cyclobenzaprine Treatment for Sexual Dysfunction,” was filed and is now nationalized in European Patent Office and U.S. (U.S. Patent Application No. 18/698,483). The claims of these applications are directed to methods using pharmaceutical compositions and combinations for treating sexual dysfunction with cyclobenzaprine or pharmaceutically acceptable salts of cyclobenzaprine.

On October 25, 2016 and July 28, 2020, U.S. Patent No. 9,474,728 and U.S. Patent No. 10,722,478, entitled “Methods and Compositions for Treating Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine”, issued, respectively. The claims are directed to a method for monitoring the effectiveness of cyclobenzaprine treatment for disordered sleep and method for reducing CAP rates A2 or A3 by treating a subject with a pharmaceutical composition comprising cyclobenzaprine.

On December 11, 2018, International Patent Application No. PCT/IB2018/001509, entitled “Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions,” was filed. The PCT application is now nationalized in 16 countries. The claims are directed to methods for treating or preventing agitation, cognitive decline, psychosis, and associated symptoms thereof using pharmaceutical compositions and combinations with cyclobenzaprine or pharmaceutically acceptable salts of cyclobenzaprine.

On November 28, 2023, U.S. Patent No. 11,826,321, entitled “Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions,” issued. The claims are directed to a method for treating or preventing one or more agitation associated symptoms comprising administering a eutectic of cyclobenzaprine HCl and mannitol.

On August 20, 2019, International Patent Application No. PCT/IB2019/000940, entitled “Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder,” was filed. The PCT application is now nationalized in 18 countries. The claims are directed to methods of treating acute stress disorder or post-traumatic stress disorder in a subject who has experienced a traumatic event using pharmaceutical compositions with cyclobenzaprine, amitriptyline or pharmaceutically acceptable salts of cyclobenzaprine or amitriptyline.

On November 19, 2021, International Patent Application No. PCT/US2021/060011, entitled “Cyclobenzaprine Treatment for Alcohol Use Disorder,” was filed. The PCT application is now nationalized in 13 countries. The claims are directed to methods for treating alcohol use disorder and associated symptoms using pharmaceutical compositions with cyclobenzaprine or pharmaceutically acceptable salts of cyclobenzaprine.

On December 7, 2021, International Patent Application No. PCT/US2021/062244, entitled, “Cyclobenzaprine Treatment for Fibromyalgia,” was filed. The PCT is now nationalized in 15 countries. The claims are directed to methods for treating fibromyalgia and its associated symptoms of pain, sleep disturbance and/or fatigue by transmucosally administering a eutectic of cyclobenzaprine hydrochloride and mannitol in dosage units with a basifying agent.

On June 21, 2023, U.S. non-provisional Patent Application No. 18/212,500 and International Patent Application No. PCT/US2023/025895, entitled “Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC),” were filed. The PCT is now nationalized in 9 countries. The claims are directed to methods of treating PASC or one or more associated symptoms comprising administering cyclobenzaprine or a pharmaceutically acceptable salts of cyclobenzaprine.

On December 19, 2024, U.S. non-provisional Patent Application No. 18/988,194 and International Patent Application No. PCT/US2024/061125, entitled “Early Onset Response, Favorable Tolerability, and Side Effect Profile in the Treatment of Fibromyalgia,” were filed. The claims are directed to methods for treating or managing fibromyalgia and its associated symptoms in subjects characterized by an early onset of one or more of: (1) a reduction in widespread pain; (2) a reduction in sleep disturbance; (3) a reduction in fatigue; or (4) an improved sleep quality. The claims are also directed to methods for preventing or avoiding clinically meaningful changes in mean weight, in mean systolic blood pressure or mean diastolic blood pressure, or a decline in sexual functioning.

On January 23, 2025, International Patent Application No. PCT/US2025/012803, entitled Cyclobenzaprine Treatment for Acute Stress Reaction or Acute Stress Disorder,” was filed. The claims are directed to methods for treating or preventing acute stress reaction (ASR) or acute stress disorder (ASD) and associated symptoms thereof using a composition with cyclobenzaprine or its salts in.

TNX-1900 — Oxytocin-Based Treatments for ~~Obesity,~~the Treatment of Binge Eating ~~Disorders~~Disorder, ~~Pain~~Adolescent Obesity, ~~Insulin~~Bone ~~Resistance~~Health in Pediatric Autism, and Arginine-Vasopressin ~~Diabetes~~Deficiency

We have acquired the migraine and pain treatment technologies of Trigemina, Inc., and have assumed its license rights to related technologies from The Board of Trustees of the Leland Stanford Junior University. TNX-1900, an enhanced formulation of nasal oxytocin, has demonstrated activity in several non-clinical studies in pain, including migraine.

As part of our acquisition, we acquired International Patent Application No. PCT/US2016/012512, filed on January 7, 2016, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use” (nationalized in 13 countries). We also acquired U.S. Patent Nos. 9,629,894 and 11,389,473, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use”, which will expire in January 2036, excluding any patent term extensions. On July 1, 2022, Chinese Patent No. ZL201680013809.5, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use,” issued. On October 4, 2023, European Patent No. 3242676, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use,” issued.

We also acquired International Patent Application No. PCT/US2017/027265, filed April 12, 2017, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use” (nationalized in 9 countries). On December 3, 2024, U.S. Patent No. 12,156,897, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use,” issued. The patent, which claims methods for treating autism spectrum disorder, social anxiety disorder, or a social communication disorder, will expire in April 2037, excluding any patent term extensions. On January 1, 2023, Chinese Patent No. ZL201780036185.3, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use,” issued. On November 13, 2025 Japan Patent No. 7093559, entitled “Magnesium-Containing Oxytocin Formulations and Methods of Use,” issued.

We also have rights to International Patent Application No. PCT/US2019/020419, filed on April 12, 2017, entitled “Labeled Oxytocin and Method of Manufacture and Use” (nationalized in the U.S., European Patent Office and Japan). On April 30, 2024, U.S. Patent No. 11,970,554, entitled “Labeled Oxytocin and Method of Manufacture and Use,” issued. On November 11, 2025, U.S. Patent No. 12,466,855, entitled “Labeled Oxytocin and Method of Manufacture and Use,” issued.

We have entered into an exclusive license to the University of Geneva’s technology for using oxytocin to treat insulin resistance and related syndromes, including obesity. This license expands our intranasal potentiated oxytocin development program, TNX-1900, into cardiometabolic syndromes. Under the license, we have rights to European Patent No. EP2571511B1, entitled “New Uses of Oxytocin-like Molecules and Related Methods.” We also have rights to U.S. Patent No. 9,101,569, entitled “Methods for the Treatment of Insulin Resistance.” The U.S. and non-U.S. patents expire in May 2031, excluding any patent term adjustments or extensions.

We are developing oxytocin peptide analogs for headache disorders. On March 18, 2025, we filed International Patent Application No. PCT/US2025/020483, entitled “Oxytocin Peptide Analogs.”

TNX-2900 — Oxytocin-Based Therapeutics Treatments for Prader-Willi Syndrome (PWS)

We have licensed technology using oxytocin-based therapeutics for the treatment of PWS and non-organic failure to thrive disease from the French National Institute of Health and Medical Research (INSERM). The co-exclusive license relates to TNX-2900, an intranasal potentiated oxytocin, for the treatment of Prader-Willi syndrome and other feeding disorders. Under the license, we have rights to European Patent No. EP2575853B1, entitled “Methods and Pharmaceutical Composition for the Treatment of a Feeding Disorder with Early-Onset in a Patient”; U.S. Patent No. 8,853,158, entitled “Methods for the Treatment of a Feeding Disorder with Onset During Neonate Development Using an Agonist of the Oxytocin Receptor”; and U.S. Patent No. 9,125,862, entitled “Methods for the Treatment of Prader-Willi-like Syndrome or Non-Organic Failure to Thrive (NOFITT) Feeding Disorder Using an Agonist of the Oxytocin Receptor.” The U.S. and non-U.S. patents expire in May 2031, excluding any patent term extensions.

TNX-1300 — Cocaine Intoxication Treatment

We have licensed rights from The Trustees of Columbia University in the City of New York, The Regents of the University of Michigan, and University of Kentucky Research Foundation to develop a potential product, TNX-1300, for the treatment of cocaine intoxication. The licensed patents are directed to mutant cocaine esterase polypeptides and methods of using these polypeptides as anti-cocaine therapeutics. They include U.S. Patent Nos. 8,318,156 and 9,200,265, entitled “Anti-Cocaine Compositions and Treatment” and various counterpart patents outside of the U.S (e.g., European Patent 2046368). These patents provide TNX-1300 with US market exclusivity until February 2029, and market exclusivity outside of the U.S. until July 10, 2027, subject to any patent term extensions.

TNX-1500 — anti-CD40L Therapeutics

We are developing TNX-1500, a humanized mAb that targets CD40L for the prevention and treatment of organ transplant rejection. In this regard, we filed International Application No. PCT/EP2020/068589, entitled “Anti-CD154 antibodies and uses thereof” on July 1, 2020 (nationalized in 15 countries). We also filed International Patent Application No. PCT/US2020/028002 on April 13, 2020, entitled “Inhibitors of CD40-CD154 Binding” (nationalized in U.S., Canada, China, European Patent Office and Japan). We also filed International Patent Application No. PCT/US2022/011404, entitled “Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies” on January 6, 2022 (nationalized in 14 countries). We also filed International Patent Application No. PCT/EP2025/065085, entitled “Treatment Methods Comprising Administration of Modified CD154 Antibodies” on May 30, 2025.

On August 28, 2024, European Patent No. 3993876, entitled “Anti-CD154 Antibodies and Uses Thereof,” issued (validated in 37 countries). The claims recite an isolated antibody that binds CD154, compositions comprising the antibody, and use of the compositions for treating or preventing a transplant rejection.

On April 22, 2025, Chinese Patent No. ZL202080059891.1, entitled “Anti-CD154 antibodies and uses thereof,” issued. The claims recite an isolated antibody that binds CD154, compositions comprising the antibody, and uses of the antibody for inhibiting an immune response, treating or preventing a transplant rejection, or inhibiting xenotransplant rejection.

On November 14, 2025, Japanese Patent No. 7775080, entitled “Anti-CD154 antibodies and uses thereof,” issued. The claims recite an antibody or isolated antibody that binds CD154 and compositions comprising the antibody for use in treating or preventing a transplant rejection, inducing hematopoietic chimerism in a transplant recipient, inducing central tolerance in a transplant recipient, or inhibiting xenotransplant rejection.

TNX-801 — Live Horsepox Vaccine for Prevention of Smallpox and Mpox

We own the rights to develop a potential biodefense technology, TNX-801, a live horsepox that is being developed as a new smallpox and mpox preventing vaccine, we have filed patent applications directed to synthetic chimeric poxviruses and methods of using these poxviruses to protect individuals against smallpox. These applications include U.S. non-provisional Patent Application No. 15/802,189 and International Patent Application No. PCT/US2017/059782 (nationalized in 15 countries and filed in 4 non-PCT countries). We also own the rights to develop other vaccine candidates against smallpox. With respect to these vaccine candidates, we own International Patent Application No. PCT/US2019/030486 and the non-convention and national phase applications related thereto (nationalized in 17 countries and filed in 2 non-PCT countries). The smallpox vaccine technologies relate to proprietary forms of live horsepox and vaccinia vaccines which may be safer than ACAM2000, the only currently available replication competent, live vaccinia vaccine to protect against smallpox disease. We believe that this technology, after further development, may be of interest to biodefense agencies in the U.S. and other countries.

On May 31, 2022, U.S. Patent No. 11,345,896 was issued. The claims recite a synthetic chimeric orthopoxvirus (scOPV), a synthetic chimeric horsepox virus (scHPXV), methods of generating the scOPV and scHPXV, and compositions comprising the scOPV or scHPXV.

~~TNX-1800~~On July 22, 2025, U.S. Patent No. 12,365,879, entitled “Synthetic Chimeric Poxviruses,” issued. The claims recite methods of producing a synthetic chimeric orthopoxvirus (scOPV) and ~~TNX-1850~~a —synthetic ~~Live~~chimeric ~~Modified~~horsepox ~~Horsepox~~virus ~~Vaccine~~(scHPXV) ~~for~~and ~~Prevention~~methods of ~~COVID-19~~treating infections using the scOPV or scHPXV.

~~We are developing TNX-1800 and TNX-1850, live minimally replicative modified~~On ~~HPXVs,~~April ~~as a COVID-19 preventing vaccine against different strains of SARS-CoV-~~2~~. On February 26~~, ~~2021~~2024, weChinese ~~filed International~~ Patent ~~Application~~ No. ~~PCT/US2021/020119~~ZL201780078546.0, entitled “~~Recombinant~~Synthetic ~~Poxvirus~~Chimeric ~~Based Vaccine Against SARS-CoV-2.~~Poxviruses,” ~~On the same date, we also filed applications in Argentina and Taiwan and we filed U~~issued.S. ~~Application No. 17/187,678.~~ The ~~PCT~~claims ~~application is now nationalized in 19 countries. These applications~~recite ~~are~~a ~~directed to~~ synthetic ~~poxviruses~~chimeric ~~comprising~~orthopoxvirus ~~a SARS-CoV-2 virus protein~~(scOPV), ~~poxvirus delivery vectors for SARS-CoV-2 virus proteins and~~ methods of ~~using~~producing ~~these~~an ~~modified~~scOPV, ~~poxviruses~~compositions tocomprising ~~protect~~the ~~individuals~~scOPV, ~~against~~and ~~COVID-19~~uses of the scOPV.

TNX-1800 and TNX-1850 — Live Modified Horsepox Vaccine for Prevention of COVID

We are developing TNX-1800 and TNX-1850, live minimally replicative modified HPXVs, as a COVID preventing vaccine against different strains of SARS-CoV-2. On February 26, 2021, we filed International Patent Application No. PCT/US2021/020119, entitled “Recombinant Poxvirus Based Vaccine Against SARS-CoV-2.” On the same date, we also filed applications in Argentina and Taiwan and we filed U.S. Application No. 17/187,678. The PCT application is now nationalized in 19 countries. These applications are directed to synthetic poxviruses comprising a SARS-CoV-2 virus protein, poxvirus delivery vectors for SARS-CoV-2 virus proteins and methods of using these modified poxviruses to protect individuals against COVID.

TNX-1700 — Recombinant Trefoil Family Factor 2 (rTFF2) to Treat Gastric and Colorectal Cancers

We have licensed rights from The Trustees of Columbia University in the City of New York to develop a potential product, TNX-1700, for the treatment of gastric and colorectal cancers. The licensed patents are directed to rTFF2 compositions and methods of treatment. The licensed patents, U.S. Patent No. 10,124,037 and U.S. Patent No. 11,167,010~~. The~~, ~~licensed patents~~ provide TNX-1700 with US market exclusivity until April 2033, subject to any patent term extensions. On August 27, 2020, we filed International Patent Application No. PCT/IB2020/000699 entitled “Modified TFF2 Polypeptides.” The PCT application is now nationalized in 12 countries.

TNX-3900 — Antiviral Drugs

We have acquired the intellectual property rights of Healion Bio, Inc. to develop antiviral drugs. These rights include International Patent Application No. PCT/US2021/032461 (nationalized in 6 countries) and U.S. Patent Application No. 18/055,596, both entitled “Compositions and Methods for Increasing Efficacy of a Drug.”

TNX-4300 — Estianeptine for Psychiatric and Neurodegenerative Diseases

We are developing TNX-4300, the (S)-isomer of tianeptine, for psychiatric and neurodegenerative diseases. On March 27, 2024, we filed International Patent Application No. PCT/US2024/021799, entitled “(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor.”

Zembrace and Tosymra — Sumatriptan

We have acquired the intellectual property rights of Zembrace SymTouch and Tosymra and their uses in treating migraine from Upsher-Smith Laboratories, LLC. These rights include U.S. Patent No. 9,211, 282, U.S. Patent No. 9,610,280, U.S. Patent No. 9,974,770, U.S. Patent No. 10,603,305, U.S. Patent No. 11,337,962, U.S. Patent No. 10,537,554, and U.S. Patent No. 11,364, 224. These rights also include International Patent Application No. PCT/US2016/015961, entitled “Pharmaceutical Composition Comprising Sumatriptan for Treating Migraine,” (nationalized in 7 countries, excluding rights in Brazil and China) and International Patent Application No. PCT/IB2010/001708, entitled “Formulations Comprising Triptan Compounds,” (nationalized in 11 countries, excluding rights in Brazil, Russia, India, and China).

Trade Secrets

In addition to patents, we rely on trade secrets and know-how to develop and maintain our competitive position. For example, significant aspects of our proprietary technology platform are based on unpatented trade secrets and know-how. Trade secrets and know-how can be difficult to protect. We seek to protect our proprietary technology and processes, in part, by confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors, and commercial partners. These agreements are designed to protect our proprietary information and, in the case of the invention assignment agreements, to grant us ownership of technologies that are developed through a relationship with a third party. We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems. While we have confidence in these individuals, organizations and systems, agreements or security measures may be breached, and we may not have adequate remedies for any breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors. To the extent that our contractors use intellectual property owned by others in their work for us, disputes may arise as to rights in related or resulting inventions and know-how.

Issued Patents

Our current patents owned or licensed include:

Anti-Cocaine Therapeutics

Patent No.	Title	Country / Region	Expiration Date
8,318,156	Anti-Cocaine Compositions and Treatment	U.S.A.	February 14, 2029
9,200,265	Anti-Cocaine Compositions and Treatment	U.S.A.	December 30, 2027
2007272955	Anti-Cocaine Compositions and Treatment	Australia	July 10, 2027
2014201653	Anti-Cocaine Compositions and Treatment	Australia	July 10, 2027
2657246	Anti-Cocaine Compositions and Treatment	Canada	July 10, 2027
612929	Anti-Cocaine Compositions and Treatment	New Zealand	July 10, 2027
2046368 (602007045044.6 in Germany; 502016000056543 in Italy)	Anti-Cocaine Compositions and Treatment	European Patent Office – Germany, Spain, France, United Kingdom, and Italy	July 10, 2027
2009/00197	Anti-Cocaine Compositions and Treatment	South Africa	July 10, 2027
305483	Anti-Cocaine Compositions and Treatment	Mexico	July 10, 2027
196411	Mutants of Cocaine Esterase (CocE) Polypeptide, Nucleic Acids Encoding Them, Pharmaceutical Compositions Comprising Them and Uses Thereof	Israel	July 10, 2027

Sublingual CBP/Amitriptyline

Patent No.	Title	Country / Region	Expiration Date
6259452	Compositions and Methods for Transmucosal Absorption	Japan	June 14, 2033
631144	Compositions and Methods for Transmucosal Absorption	New Zealand	June 14, 2033
I590820	Compositions and Methods for Transmucosal Absorption	Taiwan R.O.C.	June 14, 2033
2013274003	Compositions and Methods for Transmucosal Absorption	Australia	June 14, 2033
I642429	Compositions and Methods for Transmucosal Absorption	Taiwan R.O.C.	June 14, 2033
726488	Compositions and Methods for Transmucosal Absorption	New Zealand	June 14, 2033
I683660	Compositions and Methods for Transmucosal Absorption	Taiwan R.O.C.	June 14, 2033
2018241128	Compositions and Methods for Transmucosal Absorption	Australia	June 14, 2033
2876902	Compositions and Methods for Transmucosal Absorption	Canada	June 14, 2033
IDP000076019	Compositions and Methods for Transmucosal Absorption	Indonesia	June 14, 2033
382516	Compositions and Methods for Transmucosal Absorption	Mexico	June 14, 2033
2861223 (AL/P/2022/458 in Albania; P20221325T in Croatia; 602013082236.0 in Germany; 3111421 in Greece; 502022000069474 in Italy; P912561 in North Macedonia; SM-T-202200436 in San Marino; RS63822B1 in Serbia; and 2022-GE-787024 in Turkey)	Compositions and Methods for Transmucosal Absorption	European Patent Office – Italy, Albania, Austria, Belgium, Bulgaria, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, United Kingdom, San Marino, Serbia, Croatia, North Macedonia and Turkey	June 14, 2033
236268	Compositions for Transmucosal Delivery and Uses Thereof	Israel	June 14, 2033
2015/00288	Compositions and Methods for Transmucosal Absorption	South Africa	June 14, 2033
BR112014031394-6	Compositions and Methods for Transmucosal Absorption	Brazil	June 14, 2033
1209361	Compositions and Methods for Transmucosal Absorption	Hong Kong	June 14, 2033
398632	Compositions and Methods for Transmucosal Absorption	Mexico	June 14, 2033
A059897	Compositions and Methods for Transmucosal Absorption	Venezuela	June 14, 2033
MY-194495-A	Compositions and Methods for Transmucosal Absorption	Malaysia	June 14, 2033
3,118,913	Compositions and Methods for Transmucosal Absorption	Canada	June 14, 2033
10201605407T	Compositions and Methods for Transmucosal Absorption	Singapore	June 14, 2033

38 30

CBP – Depression

Patent No.	Title	Country / Region	Expiration Date
11,998,516	Methods and Compositions for Treating Depression Using Cyclobenzaprine	U.S.A.	March 5, 2032
2012225548	Methods and Compositions for Treating Depression Using Cyclobenzaprine	Australia	March 6, 2032
2016222412	Methods and Compositions for Treating Depression Using Cyclobenzaprine	Australia	March 6, 2032
2018204633	Methods and Compositions for Treating Depression Using Cyclobenzaprine	Australia	March 6, 2032
2020203874	Methods and Compositions for Treating Depression Using Cyclobenzaprine	Australia	March 6, 2032
614725	Methods and Compositions for Treating Depression Using Cyclobenzaprine	New Zealand	March 6, 2032
714294	Methods and Compositions for Treating Depression Using Cyclobenzaprine	New Zealand	March 6, 2032
2,829,200	Methods and Compositions for Treating Depression Using Cyclobenzaprine	Canada	March 6, 2032
2683245 (AL/P/2020/15 in Albania; P20200142 in Croatia; MK/P/2020/68 in North Macedonia; 602012066717.6 in Germany; 3103147 in Greece; HU/E048596 in Hungary; 502020000014740 in Italy; 10476 in North Macedonia; SM-T-202000083 in San Marino; 60240 in Serbia; 2773834 in Spain; and 2020-GE-5216 in Turkey)	Methods and Compositions for Treating Depression Using Cyclobenzaprine	European Patent Office – Albania, Austria, Belgium, Bulgaria, Switzerland, Cyprus, Czechia, Germany, Denmark, Estonia, Spain, Finland, France, United Kingdom, Greece, Croatia, Hungary, Ireland, Iceland, Italy, Lithuania, Luxembourg, Latvia, Monaco, Republic of North Macedonia, Malta, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Sweden, Slovenia, Slovakia, San Marino, and Turkey	March 6, 2032

CBP – PTSD

Patent No.		Title		Country / Region		Expiration Date
9,918,948		Methods and Compositions for Treating Symptoms Associated with Post-Traumatic Stress Disorder Using Cyclobenzaprine		U.S.A.		November 18, 2030

CBP Fatigue

Patent No.	Title	Country / Region	Expiration Date
9,474,728	Methods and Compositions for Treating Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine	U.S.A.	June 9, 2031
10,722,478	Methods and Compositions for Treating Fatigue Associated with Disordered Sleep Using Very Low Dose Cyclobenzaprine	U.S.A.	June 9, 2031

CBP – Agitation in Neurodegenerative Condition

Patent No.	Title	Country / Region	Expiration Date
11,826,321	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	U.S.A.	December 11, 2038
275289	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Israel	December 11, 2038
411601	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Mexico	December 11, 2038
3,083,341	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Canada	December 11, 2038
2020/03243	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	South Africa	December 11, 2038
MY-207073-A	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Malaysia	December 11, 2038
2018383098	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Australia	December 11, 2038

CBP/Amitriptyline Eutectic Formulations

Patent No.	Title	Country / Region	Expiration Date
631152	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	New Zealand	March 14, 2034
747040	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	New Zealand	March 14, 2034
9,636,408	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	U.S.A.	March 14, 2034
9,956,188	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	U.S.A.	March 14, 2034
10,117,936	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	U.S.A.	March 14, 2034
10,322,094	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	U.S.A.	March 14, 2034
10,357,465	Eutectic Formulations of Cyclobenzaprine Hydrochloride	U.S.A.	September 18, 2035
10,736,859	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	U.S.A.	March 14, 2034
10,864,175	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	U.S.A.	March 14, 2034
10,864,176	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	U.S.A.	March 14, 2034
11,026,898	Eutectic Formulations of Cyclobenzaprine Hydrochloride	U.S.A.	September 18, 2035
11,737,991	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	U.S.A.	March 14, 2034
11,839,594	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	U.S.A.	March 14, 2034
6310542	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Japan	March 14, 2034
6614724	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Japan	September 18, 2035
6717902	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Japan	September 18, 2035
6088	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Saudi Arabia	March 14, 2034
ZL201480024011.1	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	China	March 14, 2034
ZL.201580050140.2	Eutectic Formulations of Cyclobenzaprine Hydrochloride	China	September 18, 2035
2014233277	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Australia	March 14, 2034
2015317336	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Australia	September 18, 2035
I661825	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Taiwan R.O.C.	March 14, 2034
I740136	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Taiwan R.O.C.	March 14, 2034
IDP000055516	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Indonesia	March 14, 2034
IDP000063221	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Indonesia	September 18, 2035
IDP000076872	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Indonesia	March 14, 2034
2968992 (1211591 in Austria, CZ2014-762323 in Czechia, 602014058260.5 in Germany, E018723 in Estonia, P20200055 in Croatia, 201361792757 P in Ireland, 2020.67 in Monaco, P-2020/0094 in Serbia, 201431487 in Slovenia, 33269 in Slovakia, 2020000045 in San Marino, AL/P/2019/906 in Albania, MK/P/2020/67 in Republic of North Macedonia, 3102655 in Greece, 502020000007756 in Italy)	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	European Patent Office - Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Republic of North Macedonia, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom	March 14, 2034

41 32

6088	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Saudi Arabia	March 14, 2034
ZL201480024011.1	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	China	March 14, 2034
ZL.201580050140.2	Eutectic Formulations of Cyclobenzaprine Hydrochloride	China	September 18, 2035
2014233277	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Australia	March 14, 2034
2015317336	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Australia	September 18, 2035
I661825	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Taiwan R.O.C.	March 14, 2034
I740136	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Taiwan R.O.C.	March 14, 2034
IDP000055516	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Indonesia	March 14, 2034
IDP000063221	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Indonesia	September 18, 2035
IDP000076872	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Indonesia	March 14, 2034
2968992 (1211591 in Austria, CZ2014-762323 in Czechia, 602014058260.5 in Germany, E018723 in Estonia, P20200055 in Croatia, 201361792757 P in Ireland, 2020.67 in Monaco, P-2020/0094 in Serbia, 201431487 in Slovenia, 33269 in Slovakia, 2020000045 in San Marino, AL/P/2019/906 in Albania, MK/P/2020/67 in Republic of North Macedonia, 3102655 in Greece, 502020000007756 in Italy)	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	European Patent Office - Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Republic of North Macedonia, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom	March 14, 2034
3650081	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	European Patent Office - Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Republic of North Macedonia, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom	March 14, 2034
241353	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Israel	March 14, 2034
251218	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Methods of Producing Same	Israel	September 18, 2035
277814	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Methods of Producing Same	Israel	September 18, 2034
370021	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Mexico	March 14, 2034
387402	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Mexico	September 18, 2035
388137	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Mexico	March 14, 2034
2015/07443	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	South Africa	March 14, 2034

42 33

241353	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Israel	March 14, 2034
251218	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Methods of Producing Same	Israel	September 18, 2035
277814	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Methods of Producing Same	Israel	September 18, 2034
370021	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Mexico	March 14, 2034
387402	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Mexico	September 18, 2035
388137	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Mexico	March 14, 2034
2015/07443	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	South Africa	March 14, 2034
2017/01637	Eutectic Formulations of Cyclobenzaprine Hydrochloride	South Africa	September 18, 2035
BR112015022095-9	Pharmaceutical Composition, Method of Fabrication, Eutectic Composition and Use of Compositions Containing Cyclobenzaprine HCl and Mannitol	Brazil	March 14, 2034
2904812	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Canada	March 14, 2034
3119755	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Canada	March 14, 2034
2,961,822	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Canada	September 18, 2035
HK1218727	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Hong Kong	March 14, 2034
MY-186047-A	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Malaysia	September 18, 2035
398845	Eutectic Formulations of Cyclobenzaprine Hydrochloride	India	September 18, 2035
441374	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	India	March 14, 2034
MY-196014-A	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Malaysia	March 14, 2034
ZL201910263541.6	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	China	March 14, 2034
2020289838	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Australia	September 18, 2035
HK40047283	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Hong Kong	September 18, 2035
ZL202011576351.9	Eutectic Formulations of Cyclobenzaprine Hydrochloride	China	September 18, 2035
730379	Eutectic Formulations of Cyclobenzaprine Hydrochloride	New Zealand	September 18, 2035
768064	Eutectic Formulations of Cyclobenzaprine Hydrochloride	New Zealand	September 18, 2035
40013124	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Hong Kong	March 14, 2034
40030559	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Hong Kong	March 14, 2034

Analogs of CBP

Patent No.	Title	Country / Region	Expiration Date
11,517,557	Analogs of Cyclobenzaprine and Amitryptilene	U.S.A.	July 13, 2038
12,156,864	Analogs of Cyclobenzaprine and Amitryptilene	U.S.A.	July 13, 2038
7330964	Analogs of Cyclobenzaprine and Amitryptilene	Japan	July 13, 2038

Oxytocin therapeutics

Patent No.	Title	Country / Region	Expiration Date
9,629,894	Magnesium-Containing Oxytocin Formulations and Methods of Use	U.S.A.	January 7, 2036
11,389,473	Magnesium-Containing Oxytocin Formulations and Methods of Use	U.S.A.	January 7, 2036
11201705591P	Magnesium-Containing Oxytocin Formulations and Methods of Use	Singapore	January 7, 2036
388286	Magnesium-Containing Oxytocin Formulations and Methods of Use	Mexico	January 7, 2036
253347	Magnesium-Containing Oxytocin Formulations and Methods of Use	Israel	January 7, 2036
7030517	Magnesium-Containing Oxytocin Formulations and Methods of Use	Japan	January 7, 2036
ZL201680013809.5	Magnesium-Containing Oxytocin Formulations and Methods of Use	China	January 7, 2036
3242676 (P20231438 in Croatia; 602016083177.5 in Germany; 3114323 in Greece; HU/E065385 in Hungary; 65034 in Serbia; SM-T-202400020 in San Marino; and 2023-GE-778438 in Turkey)	Magnesium-Containing Oxytocin Formulations and Methods of Use	Europe – (Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom)	January 7, 2036
2017/05176	Magnesium-Containing Oxytocin Formulations and Methods of Use	South Africa	January 7, 2036
1252942	Magnesium-Containing Oxytocin Formulations and Methods of Use	Hong Kong	January 7, 2036
2020286221	Magnesium-Containing Oxytocin Formulations and Methods of Use	Australia	January 7, 2036
734097	Magnesium-Containing Oxytocin Formulations and Methods of Use	New Zealand	January 7, 2036
771693	Magnesium-Containing Oxytocin Formulations and Methods of Use	New Zealand	January 7, 2036
10-2677904	Magnesium-Containing Oxytocin Formulations and Methods of Use	Republic of Korea	January 7, 2036
7455402	Magnesium-Containing Oxytocin Formulations and Methods of Use	Japan	January 7, 2036
BR112017014545-6	Magnesium-Containing Oxytocin Formulations and Methods of Use	Brazil	January 7, 2036
BR122024008322-1	Magnesium-Containing Oxytocin Formulations and Methods of Use	Brazil	January 7, 2036
7756953	Magnesium-Containing Oxytocin Formulations and Methods of Use	Japan	January 7, 2036

43 35

7030517	Magnesium-Containing Oxytocin Formulations and Methods of Use	Japan	January 7, 2036
ZL201680013809.5	Magnesium-Containing Oxytocin Formulations and Methods of Use	China	January 7, 2036
3242676 (P20231438 in Croatia; 602016083177.5 in Germany; 3114323 in Greece; HU/E065385 in Hungary; 65034 in Serbia; SM-T-202400020 in San Marino; and 2023-GE-778438 in Turkey)	Magnesium-Containing Oxytocin Formulations and Methods of Use	Europe – (Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom)	January 7, 2036
2017/05176	Magnesium-Containing Oxytocin Formulations and Methods of Use	South Africa	January 7, 2036
1252942	Magnesium-Containing Oxytocin Formulations and Methods of Use	Hong Kong	January 7, 2036
2020286221	Magnesium-Containing Oxytocin Formulations and Methods of Use	Australia	January 7, 2036
734097	Magnesium-Containing Oxytocin Formulations and Methods of Use	New Zealand	January 7, 2036
771693	Magnesium-Containing Oxytocin Formulations and Methods of Use	New Zealand	January 7, 2036
10-2677904	Magnesium-Containing Oxytocin Formulations and Methods of Use	Republic of Korea	January 7, 2036
7455402	Magnesium-Containing Oxytocin Formulations and Methods of Use	Japan	January 7, 2036
BR112017014545-6	Magnesium-Containing Oxytocin Formulations and Methods of Use	Brazil	January 7, 2036
11,970,554	Labeled Oxytocin and Method of Manufacture and Use	U.S.A.	March 1, 2039
12,466,855	Labeled Oxytocin and Method of Manufacture and Use	U.S.A.	March 1, 2039
7093559	Magnesium-Containing Oxytocin Formulations and Methods of Use	Japan	April 12, 2037
2017250505	Magnesium-Containing Oxytocin Formulations and Methods of Use	Australia	April 12, 2037
2023203831	Magnesium-Containing Oxytocin Formulations and Methods of Use	Australia	April 12, 2037
ZL201780036185.3	Magnesium-Containing Oxytocin Formulations and Methods of Use	China	April 12, 2037
40005263	Magnesium-Containing Oxytocin Formulations and Methods of Use	Hong Kong	April 12, 2037
747221	Magnesium-Containing Oxytocin Formulations and Methods of Use	New Zealand	April 12, 2037
787097	Magnesium-Containing Oxytocin Formulations and Methods of Use	New Zealand	April 12, 2037
3,020,179	Magnesium-Containing Oxytocin Formulations and Methods of Use	Canada	April 12, 2037
12,156,897	Magnesium-Containing Oxytocin Formulations and Methods of Use	U.S.A.	April 12, 2037
417307	Magnesium-Containing Oxytocin Formulations and Methods of Use	Mexico	April 12, 2037
3442560 (602017086259.2 in Germany; and SM/T/2025/000041 in San Marino)	Magnesium-Containing Oxytocin Formulations and Methods of Use	Europe – (Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, and United Kingdom)	April 12, 2037
2575853 (2595251 in Spain)	Methods and Pharmaceutical Composition for the Treatment of a Feeding Disorder with Early-Onset in a Patient	Europe – (Spain, France, Germany, Italy, and United Kingdom)	May 25, 2031
8,853,158	Methods for the Treatment of a Feeding Disorder with Onset During Neonate Development Using an Agonist of the Oxytocin Receptor	U.S.A.	May 25, 2031
9,125,862	Methods for the Treatment of Prader-Willi-like Syndrome or Non-Organic Failure to Thrive (NOFITT) Feeding Disorder Using an Agonist of the Oxytocin Receptor	U.S.A.	May 25, 2031
2571511 (2526672 in Spain)	New Uses of Oxytocin-like Molecules and Related Methods	Europe – (Switzerland, Spain, France, Germany, Italy, United Kingdom, and Ireland)	May 17, 2031
9,101,569	Methods for the Treatment of Insulin Resistance	U.S.A.	June 22, 2031

44 36

417307	Magnesium-Containing Oxytocin Formulations and Methods of Use	Mexico	April 12, 2037
3442560 (602017086259.2 in Germany; and SM/T/2025/000041 in San Marino)	Magnesium-Containing Oxytocin Formulations and Methods of Use	Europe – (Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, and United Kingdom)	April 12, 2037
2575853 (2595251 in Spain)	Methods and Pharmaceutical Composition for the Treatment of a Feeding Disorder with Early-Onset in a Patient	Europe – (Spain, France, and United Kingdom)	May 25, 2031
8,853,158	Methods for the Treatment of a Feeding Disorder with Onset During Neonate Development Using an Agonist of the Oxytocin Receptor	U.S.A.	May 25, 2031
9,125,862	Methods for the Treatment of Prader-Willi-like Syndrome or Non-Organic Failure to Thrive (NOFITT) Feeding Disorder Using an Agonist of the Oxytocin Receptor	U.S.A.	May 25, 2031
2571511 (2526672 in Spain)	New Uses of Oxytocin-like Molecules and Related Methods	Europe – (Switzerland, Spain, France, United Kingdom, and Ireland)	May 17, 2031
9,101,569	Methods for the Treatment of Insulin Resistance	U.S.A.	June 22, 2031

Nociceptin/Orphanin FQ therapeutics

Patent No.	Title	Country / Region	Expiration Date
8,551,949	Methods for treatment of pain	U.S.A.	August 11, 2031
9,238,053	Methods for treatment of pain	U.S.A.	October 12, 2030
2010281436	Methods for treatment of pain	Australia	July 27, 2030
ZL 201080042858.4	Methods for treatment of pain	China	July 27, 2030
2459183 (602010028120.5 in Germany)	Methods for treatment of pain	Europe – (Switzerland, Germany, Denmark, France, and United Kingdom)	July 27, 2030
1169804	Methods for treatment of pain	Hong Kong	July 27, 2030
329837	Methods for treatment of pain	Mexico	July 27, 2030
597763	Methods for treatment of pain	New Zealand	July 27, 2030
10201406930U	Methods for treatment of pain	Singapore	July 27, 2030
201200584	Methods for treatment of pain	South Africa	July 27, 2030
2,769,347	Methods for treatment of pain	Canada	July 27, 2030
413642	Methods for treatment of pain	India	July 27, 2030

Tianeptine – Neurocognitive Dysfunction

Patent No.	Title	Country / Region	Expiration Date
9,314,469	Method for Treating Neurocognitive Dysfunction	U.S.A.	September 24, 2030
2723688	Method for Treating Neurodegenerative Dysfunction	Canada	April 30, 2029
2299822 (602009047361.1 in Germany; 2644511 in Spain; and E911827 in Austria)	Method for Treating Neurodegenerative Dysfunction	European Patent Office – Austria, Belgium, Switzerland, Germany, Spain, France, United Kingdom, Ireland, Luxembourg, Monaco, and Portugal	April 30, 2029
3246031 (602009057284.9 in Germany; 2727851 in Spain; and E1100344 in Austria)	Method for Treating Neurocognitive Dysfunction	European Patent Office – Austria, Belgium, Switzerland, Germany, Spain, France, United Kingdom, Ireland, Luxembourg, Monaco, and Portugal	April 30, 2029

TFF2 therapeutics

Patent No.	Title	Country / Region	Expiration Date
10,124,037	Trefoil family factor proteins and uses thereof	U.S.A	April 2, 2033
11,167,010	Trefoil family factor proteins and uses thereof	U.S.A	April 2, 2033

Synthetic Chimeric Poxviruses

Patent No.	Title	Country / Region	Expiration Date
11,345,896	Synthetic Chimeric Poxviruses	U.S.A	November 2, 2037
12,365,879	Synthetic Chimeric Poxviruses	U.S.A	November 2, 2037
397516	Synthetic Chimeric Poxviruses	Mexico	November 2, 2037
2019/02868	Synthetic Chimeric Poxviruses	South Africa	November 2, 2037
MY-200354-A	Synthetic Chimeric Poxviruses	Malaysia	November 2, 2037
2017353868	Synthetic Chimeric Poxviruses	Australia	November 2, 2037
ZL201780078546.0	Synthetic Chimeric Poxviruses	China	November 2, 2037
40014109	Synthetic Chimeric Poxviruses	Hong Kong	November 2, 2037
2022/04981	Synthetic Chimeric Poxviruses	South Africa	November 2, 2037
2024/03393	Synthetic Chimeric Poxviruses	South Africa	November 2, 2037
IDP000098405	Synthetic Chimeric Poxviruses	Indonesia	November 2, 2037
266399	Synthetic Chimeric Poxviruses	Israel	November 2, 2037
I887191	Synthetic Chimeric Poxviruses	Taiwan	November 2, 2037
752893	Synthetic Chimeric Poxviruses	New Zealand	November 2, 2037

Synthetic Vaccinia Virus

Patent No.	Title	Country / Region	Expiration Date
12,529,036	Synthetic Chimeric Vaccinia Virus	U.S.A	May 2, 2039
ZL201980029677.9	Synthetic Chimeric Vaccinia Virus	China	May 2, 2039
431454	Synthetic Chimeric Vaccinia Virus	Mexico	May 2, 2039
2019262149	Synthetic Chimeric Vaccinia Virus	Australia	May 2, 2039
HK40047064	Synthetic Chimeric Vaccinia Virus	Hong Kong	May 2, 2039
MY-212174-A	Synthetic Chimeric Vaccinia Virus	Malaysia	May 2, 2039

Poxvirus vaccine against COVID-19

Patent No.		Title		Country / Region		Expiration Date
I902763		Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus		Taiwan		February 16, 2041

Triptan Compound – Formulations

Patent No.	Title	Country / Region	Expiration Date
9,211,282	Formulations Comprising Triptan Compounds	U.S.A	July 19, 2031
9,610,280	Formulations Comprising Triptan Compounds	U.S.A	June 16, 2030
9,974,770	Formulations Comprising Triptan Compounds	U.S.A	June 16, 2030
10,603,305	Formulations Comprising Triptan Compounds	U.S.A	June 16, 2030
11,337,962	Formulations Comprising Triptan Compounds	U.S.A.	June 16, 2030
12,090,139	Formulations Comprising Triptan Compounds	U.S.A.	June 16, 2030
2010299607	Formulations Comprising Triptan Compounds	Australia	June 17, 2030
2775404	Formulations Comprising Triptan Compounds	Canada	June 17, 2030
2480197 (E760080 in Austria; 502016000000073 in Italy; 602010028995.8 in Germany; and 2553862 in Spain)	Formulations Comprising Triptan Compounds	European Patent Office - Austria, Belgium, Czechia, Denmark, France, Germany, Italy, Spain, Switzerland, and United Kingdom	June 17, 2030
5845183	Formulations Comprising Triptan Compounds	Japan	June 17, 2030
101646079	Formulations Comprising Triptan Compounds	Republic of Korea	June 17, 2030
338110	Formulations Comprising Triptan Compounds	Mexico	June 17, 2030
599344	Formulations Comprising Triptan Compounds	New Zealand	June 17, 2030
2012/02168	Formulations Comprising Triptan Compounds	South Africa	June 17, 2030

Triptan Compound – Migraine

Patent No.	Title	Country / Region	Expiration Date
10,537,554	Pharmaceutical Composition for Treating Migraine	U.S.A	January 29, 2036
11,364,224	Pharmaceutical Composition for Treating Migraine	U.S.A	January 29, 2036
12,097,183	Pharmaceutical Composition for Treating Migraine	U.S.A	January 29, 2036
385725	Pharmaceutical Composition Comprising Sumatriptan for Treating Migraine	Mexico	February 1, 2036
2994748	Pharmaceutical Composition Comprising ~~Sumatripan~~Sumatriptan for Treating Migraine	Canada	February 1, 2036

CD40 and anti-CD154 Therapeutics

Patent No.	Title	Country / Region	Expiration Date
3993876 (E1717312 in Austria; P20241602 in Croatia; 602020036714.4 in Germany; 3116977 in Greece; HU/E069680 in Hungary; 502024000056334 in Italy; 66218 in Serbia; 2994684 in Spain; and SM-T-202400527 in San Marino)	Anti-CD154 antibodies and uses thereof	Europe – (Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, San Marino, Serbia, Slovenia, Slovakia, Spain, Sweden, Switzerland, Turkey, United Kingdom)	July 1, 2040
ZL202080059891.1	Anti-CD154 antibodies and uses thereof	China	July 1, 2040
40074747	Anti-CD154 antibodies and uses thereof	Hong Kong	July 1, 2040
7775080	Anti-CD154 antibodies and uses thereof	Japan	July 1, 2040
MY-209630-A	Anti-CD154 antibodies and uses thereof	Malaysia	July 1, 2040
2022/01378	Anti-CD154 antibodies and uses thereof	South Africa	July 1, 2040

CBP - ASD and PTSD

Patent No.	Title	Country / Region	Expiration Date
420368	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Mexico	August 20, 2039
2019323764	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Australia	August 20, 2039
7691739	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Japan	August 20, 2039

CBP – Sexual dysfunction

Patent No.	Title	Country / Region	Expiration Date
ZL202180040673.8	Cyclobenzaprine Treatment for Sexual Dysfunction	China
40090080	Cyclobenzaprine Treatment for Sexual Dysfunction	Hong Kong
7780447	Cyclobenzaprine Treatment for Sexual Dysfunction	Japan

Pending Patent Applications

Our current pending patent applications are as follows:

CD40 and anti-CD154 Therapeutics

Application No.	Title	Country / Region
17/623,710	Anti-CD154 antibodies and uses thereof	U.S.A.
2020300002	Anti-CD154 antibodies and uses thereof	Australia
BR112021026410-8	Anti-CD154 antibodies and uses thereof	Brazil
BR122024022801-7	Anti-CD154 antibodies and uses thereof	Brazil
3145453	Anti-CD154 antibodies and uses thereof	Canada
202080059891.1	Anti-CD154 antibodies and uses thereof (Allowed)	China
202510443183.2	Anti-CD154 antibodies and uses thereof	China
24195755.4	Anti-CD154 antibodies and uses thereof	European Patent Office
202217004870	Anti-CD154 antibodies and uses thereof	India
P00202200763	Anti-CD154 antibodies and uses thereof	Indonesia
289354	Anti-CD154 antibodies and uses thereof	Israel
2021-578262	Anti-CD154 antibodies and uses thereof	Japan
2025-97959	Anti-CD154 antibodies and uses thereof	Japan
PI 2021007835	Anti-CD154 antibodies and uses thereof	Malaysia
PI 2024006778	Anti-CD154 antibodies and uses thereof	Malaysia
MX/a/2022/000133	Anti-CD154 antibodies and uses thereof	Mexico
784548	Anti-CD154 antibodies and uses thereof	New Zealand
822935	Anti-CD154 antibodies and uses thereof	New Zealand
11202114433Y	Anti-CD154 antibodies and uses thereof	Singapore
2022/01378	Anti-CD154 antibodies and uses thereof	South Africa
2024/09160	Anti-CD154 antibodies and uses thereof	South Africa
62022063693.5	Anti-CD154 antibodies and uses thereof (Allowed)	Hong Kong
42025108505.6	Anti-CD154 antibodies and uses thereof	Hong Kong
62022062573.0	Anti-CD154 antibodies and uses thereof	Hong Kong
18/271,098	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	U.S.A.
2022205313	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	Australia
BR112023013285-1	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	Brazil
3207098	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	Canada
202280019221.6	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	China
22701768.8	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	European Patent Office
P00202307159	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	Indonesia
304253	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	Israel
2023-541043	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	Japan
PI 2023003993	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	Malaysia
MX/a/2023/008055	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	Mexico
801414	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	New Zealand
11202305000R	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	Singapore
2023/06791	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	South Africa
62024090562.5	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	Hong Kong
62024091450.2	Methods of Inducing Immune Tolerance with Modified Anti-CD154 Antibodies	Hong Kong
3136725	Inhibitors of CD40-CD154 Binding	Canada
PCT/EP2025/065085	Treatment Methods Comprising Administration of Modified CD154 Antibodies	PCT
2021-560713	Inhibitors of CD40-CD154 Binding	Japan
17/603,260	Inhibitors of CD40-CD154 Binding	U.S.A.
202080033531.4	Inhibitors of CD40-CD154 Binding	China

48 40

CBP/Amitriptyline Eutectic Formulations

Application No.	Title	Country / Region
18/385,468	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	U.S.A.
19/230,858	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	U.S.A.
BR112017005231-8	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Brazil
BR122020020968-2	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Brazil
2,961,822	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Canada
15841528.1	Eutectic Formulations of Cyclobenzaprine Hydrochloride	European Patent Office
18101200.4	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Hong Kong
2023-188486	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Japan
2023-116057	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Japan
2025-76812	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Japan

Application No.	Title	Country / Region
PI 2023000078	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Malaysia
517381123	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Saudi Arabia
10201707528W	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride (Allowed)	Singapore
10201902203V	Eutectic Formulations of Cyclobenzaprine Hydrochloride	Singapore
2014-000391	Eutectic Formulations of Cyclobenzaprine Hydrochloride and Amitriptyline Hydrochloride	Venezuela

Sublingual CBP/Amitriptyline

Application No.	Title	Country / Region
13/918,692	Compositions and Methods for Transmucosal Absorption	U.S.A.
19/409,704	Compositions and Methods for Transmucosal Absorption	U.S.A.
P20130102101	Compositions and Methods for Transmucosal Absorption	Argentina
20230100254	Compositions and Methods for Transmucosal Absorption	Argentina
202010024102.2	Compositions and Methods for Transmucosal Absorption	China
2013/24661	Compositions and Methods for Transmucosal Absorption	Gulf Cooperation Council
2013/37088	Compositions and Methods for Transmucosal Absorption	Gulf Cooperation Council
2013/40660	Compositions and Methods for Transmucosal Absorption	Gulf Cooperation Council
42020020336.2	Compositions and Methods for Transmucosal Absorption	Hong Kong
P-00 2021 01421	Compositions and Methods for Transmucosal Absorption	Indonesia
2024-14696	Compositions and Methods for Transmucosal Absorption	Japan
10202401383X	Compositions and Methods for Transmucosal Absorption	Singapore

CBP – Agitation in Neurodegenerative Condition

Application No.	Title	Country / Region
2018383098	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions (Allowed)	Australia
BR112020011345-0	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Brazil
201880079917.1	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	China
18847270.8	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	European Patent Office
P00202004178	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Indonesia
202017023747	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	India
2020-531611	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Japan
62020022462.9	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Hong Kong
62021029558.5	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Hong Kong
42024101171.7	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Hong Kong
10202303446R	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Singapore
2023-186441	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Japan
2026-6717	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	Japan
202410396685.X	Cyclobenzaprine Treatment for Agitation, Psychosis and Cognitive Decline in Dementia and Neurodegenerative Conditions	China

50 41

Analogs of CBP

Application No.	Title	Country / Region
18/950,382 3069699 201880050758.2 18831505.5	Analogs of Cyclobenzaprine and Amitriptyline Analogs of Cyclobenzaprine and Amitriptyline Analogs of Cyclobenzaprine and Amitriptyline Analogs of Cyclobenzaprine and Amitriptyline	U.S.A. Canada China European Patent Office
18/950,382	Analogs of Cyclobenzaprine and Amitriptyline	U.S.A.
3069699	Analogs of Cyclobenzaprine and Amitriptyline	Canada
201880050758.2	Analogs of Cyclobenzaprine and Amitriptyline	China
18831505.5	Analogs of Cyclobenzaprine and Amitriptyline	European Patent Office
2024-027046	Analogs of Cyclobenzaprine and Amitriptyline	Japan

CBP – ASD and PTSD

Application No.	Title	Country / Region
2019/38140	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Gulf Cooperation Council
108129709	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Taiwan R.O.C.
17/269,106	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	U.S.A.
2019323764	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Australia
PI2021000802	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Malaysia
772889	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	New Zealand
813830	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	New Zealand
BR112021003107-3	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Brazil
3109258	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Canada
201980062283.3	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	China
202510112547.9	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	China
19802247.7	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	European Patent Office
62021045278.0	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Hong Kong
62022046260.5	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Hong Kong
42025114696.5	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Hong Kong
202117011223	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	India
P00202101716	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Indonesia
280921	Cyclobenzaprine or Amitriptyline Containing Compositions for Use in Treating Stress Disorders	Israel
2021-509201	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Japan
2025-32822	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Japan
10-2024-02502Q	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	Singapore
2021/01121	Methods of Treating Acute Stress Disorder and Posttraumatic Stress Disorder	South Africa

CBP – Fibromyalgia

Application No.	Title	Country / Region
18/265,525	Cyclobenzaprine Treatment for Fibromyalgia	U.S.A.
19/421,039	Cyclobenzaprine Treatment for Fibromyalgia	U.S.A.
2021396509	Cyclobenzaprine Treatment for Fibromyalgia	Australia
3204202	Cyclobenzaprine Treatment for Fibromyalgia	Canada
202180089897.8	Cyclobenzaprine Treatment for Fibromyalgia	China
21844438.8	Cyclobenzaprine Treatment for Fibromyalgia	European Patent Office
62024089847.3	Cyclobenzaprine Treatment for Fibromyalgia	Hong Kong
62024090216.8	Cyclobenzaprine Treatment for Fibromyalgia	Hong Kong
202317044026	Cyclobenzaprine Treatment for Fibromyalgia	India
P00202306147	Cyclobenzaprine Treatment for Fibromyalgia	Indonesia
303497	Cyclobenzaprine Treatment for Fibromyalgia	Israel
2023-542924	Cyclobenzaprine Treatment for Fibromyalgia	Japan
PI 2023003286	Cyclobenzaprine Treatment for Fibromyalgia	Malaysia
MX/a/2023/006720	Cyclobenzaprine Treatment for Fibromyalgia	Mexico
800700	Cyclobenzaprine Treatment for Fibromyalgia	New Zealand
523441103	Cyclobenzaprine Treatment for Fibromyalgia	Saudi Arabia
524462219	Cyclobenzaprine Treatment for Fibromyalgia	Saudi Arabia
10202403823V	Cyclobenzaprine Treatment for Fibromyalgia	Singapore
2023/06139	Cyclobenzaprine Treatment for Fibromyalgia	South Africa

CBP – Fibromyalgia (Early Onset Response, Favorable Tolerability, and Side Effect Profile)

Application No.	Title	Country / Region
PCT/US2024/061125	Early Onset Response, Favorable Tolerability, and Side Effect Profile in the Treatment of Fibromyalgia	PCT
18/988,194	Early Onset Response, Favorable Tolerability, and Side Effect Profile in the Treatment of Fibromyalgia	U.S.A.

CBP – Acute Stress Reaction or Acute Stress Disorder

Application No.		Title		Country / Region
PCT/US2025/012803		Cyclobenzaprine Treatment for Acute Stress Reaction or Acute Stress Disorder		PCT

CBP – Alcohol Use Disorder

Application No.	Title	Country / Region
18/037,815	Cyclobenzaprine Treatment for Alcohol Use Disorder	U.S.A.
2021382668	Cyclobenzaprine Treatment for Alcohol Use Disorder	Australia
112023009731-2	Cyclobenzaprine Treatment for Alcohol Use Disorder	Brazil
3202722	Cyclobenzaprine Treatment for Alcohol Use Disorder	Canada
202180088339.X	Cyclobenzaprine Treatment for Alcohol Use Disorder	China
21827298.7	Cyclobenzaprine Treatment for Alcohol Use Disorder	European Patent Office
62024087606.5	Cyclobenzaprine Treatment for Alcohol Use Disorder	Hong Kong
62024089500.8	Cyclobenzaprine Treatment for Alcohol Use Disorder	Hong Kong
202317038485	Cyclobenzaprine Treatment for Alcohol Use Disorder	India
303050	Cyclobenzaprine Treatment for Alcohol Use Disorder	Israel
2023-530204	Cyclobenzaprine Treatment for Alcohol Use Disorder	Japan
MX/a/2023/005899	Cyclobenzaprine Treatment for Alcohol Use Disorder	Mexico
800112	Cyclobenzaprine Treatment for Alcohol Use Disorder	New Zealand
11202303835Y	Cyclobenzaprine Treatment for Alcohol Use Disorder	Singapore
10202501271X	Cyclobenzaprine Treatment for Alcohol Use Disorder	Singapore
2023/05747	Cyclobenzaprine Treatment for Alcohol Use Disorder	South Africa

CBP – Sexual dysfunction

Application No.	Title	Country / Region
17/226,058	Cyclobenzaprine Treatment for Sexual Dysfunction	U.S.A
2021253592	Cyclobenzaprine Treatment for Sexual Dysfunction	Australia
3179754	Cyclobenzaprine Treatment for Sexual Dysfunction	Canada
202180040673.8	Cyclobenzaprine Treatment for Sexual Dysfunction (Allowed)	China
21721779.3	Cyclobenzaprine Treatment for Sexual Dysfunction (Allowed)	European Patent Office
21721779.3	Cyclobenzaprine Treatment for Sexual Dysfunction	European Patent Office
2025-172812	Cyclobenzaprine Treatment for Sexual Dysfunction	Japan
2022-562023	Cyclobenzaprine Treatment for Sexual Dysfunction	Japan
62023077251.4	Cyclobenzaprine Treatment for Sexual Dysfunction	Hong Kong
62023078964.1	Cyclobenzaprine Treatment for Sexual Dysfunction	Hong Kong
62025103395.2	Cyclobenzaprine Treatment for Sexual Dysfunction	Hong Kong
18/698,483	Cyclobenzaprine for Treatment or Prevention of Sexual Dysfunction Associated with Mental Health Conditions in Female Patients	U.S.A.
22800445.3	Cyclobenzaprine for Treatment or Prevention of Sexual Dysfunction Associated with Mental Health Conditions in Female Patients	European Patent Office

CBP – Post-Acute Sequelae of SARS-CoV-2 (PASC)

Application No.	Title	Country / Region
18/212,500	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	U.S.A.
2023286504	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	Australia
36260042	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	Canada
Not Yet Assigned	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	China
202380055899.4	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	China
23744274.4	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	European Patent Office
62025114250.6	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	Hong Kong
62025114926.1	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	Hong Kong
317836	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	Israel
2024-575083	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	Japan
MX/a/2025/000142	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	Mexico
817589	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	New Zealand
2025/00293	Cyclobenzaprine Treatment for Post-Acute Sequelae of (SARS)-CoV-2 Infection (PASC)	South Africa

Oxytocin therapeutics

Application No.	Title	Country / Region
2024203428	Magnesium-Containing Oxytocin Formulations and Methods of Use	Australia
BR122024008322-1	Magnesium-Containing Oxytocin Formulations and Methods of Use	Brazil
2972975	Magnesium-Containing Oxytocin Formulations and Methods of Use (Allowed)	Canada
2972975	Magnesium-Containing Oxytocin Formulations and Methods of Use	Canada
42024096348.8	Magnesium-Containing Oxytocin Formulations and Methods of Use	Hong Kong
23201255.9	Magnesium-Containing Oxytocin Formulations and Methods of Use	European Patent Office
2024-33983	Magnesium-Containing Oxytocin Formulations and Methods of Use	Japan
2025-165798	Magnesium-Containing Oxytocin Formulations and Methods of Use	Japan
18/621,985	Labeled Oxytocin and Method of Manufacture and Use	U.S.A.
19710979.6	Labeled Oxytocin and Method of Manufacture and Use	European Patent Office
2020-545532	Labeled Oxytocin and Method of Manufacture and Use	Japan
2025-230634	Labeled Oxytocin and Method of Manufacture and Use	Japan
2024-9405	Labeled Oxytocin and Method of Manufacture and Use	Japan
2025-230635	Labeled Oxytocin and Method of Manufacture and Use	Japan
18/921,777	Magnesium-Containing Oxytocin Formulations and Methods of Use	U.S.A.
3,020,179	Magnesium-Containing Oxytocin Formulations and Methods of Use (Allowed)	Canada
2023100344997	Magnesium-Containing Oxytocin Formulations and Methods of Use	China
24214056.4	Magnesium-Containing Oxytocin Formulations and Methods of Use	European Patent Office
2024-196703	Magnesium-Containing Oxytocin Formulations and Methods of Use	Japan
747221	Magnesium-Containing Oxytocin Formulations and Methods of Use	New Zealand
2025256187	Magnesium-Containing Oxytocin Formulations and Methods of Use	Australia
787097	Magnesium-Containing Oxytocin Formulations and Methods of Use	New Zealand
2023203831	Magnesium-Containing Oxytocin Formulations and Methods of Use	Australia
42023079422.4	Magnesium-Containing Oxytocin Formulations and Methods of Use	Hong Kong
42025113914.3	Magnesium-Containing Oxytocin Formulations and Methods of Use	Hong Kong
MX/a/2023/008840	Magnesium-Containing Oxytocin Formulations and Methods of Use	Mexico
PCT/US2025/020483	Oxytocin Peptide Analogs	PCT

53 44

Nociceptin/Orphanin FQ therapeutics

Application No.	Title	Country / Region
BR122021007932-3	Methods for Treatment of Pain	Brazil

Synthetic Chimeric Poxviruses

Application No.	Title	Country / Region
17/827,320	Synthetic Chimeric Poxviruses	U.S.A.
19/249,853	Synthetic Chimeric Poxviruses	U.S.A.
19/249,868	Synthetic Chimeric Poxviruses	U.S.A.
P 20170103043	Synthetic Chimeric Poxviruses	Argentina
2017/34209	Synthetic Chimeric Poxviruses	Gulf Cooperation Council
2017/41626	Synthetic Chimeric Poxviruses	Gulf Cooperation Council
106137976	Synthetic Chimeric Poxviruses (Allowed)	Taiwan R.O.C.
BR112019008781-8	Synthetic Chimeric Poxviruses	Brazil
BR112019008781-9	Synthetic Chimeric Poxviruses	Brazil
3,042,694	Synthetic Chimeric Poxviruses	Canada
17868045.0	Synthetic Chimeric Poxviruses	European Patent Office
201917021814 PID201904682	Synthetic Chimeric Poxviruses Synthetic Chimeric Poxviruses	India Indonesia
201917021814	Synthetic Chimeric Poxviruses	India
266399 2019-545700	Synthetic Chimeric Poxviruses (Allowed) Synthetic Chimeric Poxviruses	Israel Japan
319942	Synthetic Chimeric Poxviruses	Israel
2019-545700	Synthetic Chimeric Poxviruses	Japan
2024-93677	Synthetic Chimeric Poxviruses	Japan
752893 11201903893P	Synthetic Chimeric Poxviruses Synthetic Chimeric Poxviruses	New Zealand Singapore
11201903893P	Synthetic Chimeric Poxviruses (Allowed)	Singapore
2024/03393	Synthetic Chimeric Poxviruses	South Africa
2025/03540	Synthetic Chimeric Poxviruses	South Africa
2017-000418	Synthetic Chimeric Poxviruses	Venezuela
62020003684.1	Synthetic Chimeric Poxviruses	Hong Kong
792675	Synthetic Chimeric Poxviruses	New Zealand
P00202402600	Synthetic Chimeric Poxviruses	Indonesia
113144133	Synthetic Chimeric Poxviruses	Taiwan

Synthetic Vaccinia Virus

Application No.	Title	Country / Region
2019/37492	Synthetic Chimeric Vaccinia Virus	Gulf Cooperation Council
2019/41458	Synthetic Chimeric Vaccinia Virus	Gulf Cooperation Council
20190101165	Synthetic Chimeric Vaccinia Virus	Argentina
108115290	Synthetic Chimeric Vaccinia Virus	Taiwan R.O.C.
17/050,946	Synthetic Chimeric Vaccinia Virus	U.S.A.
2019262149	Synthetic Chimeric Vaccinia Virus	Australia
BR112020022181-3	Synthetic Chimeric Vaccinia Virus	Brazil
3099330	Synthetic Chimeric Vaccinia Virus	Canada
201980029677.9	Synthetic Chimeric Vaccinia Virus	China
202510639606.8	Synthetic Chimeric Vaccinia Virus	China
19796145.1	Synthetic Chimeric Vaccinia Virus	European Patent Office
202017052398	Synthetic Chimeric Vaccinia Virus	India
P00202008694	Synthetic Chimeric Vaccinia Virus	Indonesia
278419	Synthetic Chimeric Vaccinia Virus	Israel
2024-28557	Synthetic Chimeric Vaccinia Virus	Japan
PI 2020005696	Synthetic Chimeric Vaccinia Virus	Malaysia
2025-151400	Synthetic Chimeric Vaccinia Virus	Japan
MX/a/2020/011586	Synthetic Chimeric Vaccinia Virus	Mexico
768999	Synthetic Chimeric Vaccinia Virus	New Zealand
10202401171Y	Synthetic Chimeric Vaccinia Virus	Singapore
2020/06350	Synthetic Chimeric Vaccinia Virus	South Africa
62021036744.2	Synthetic Chimeric Vaccinia Virus	Hong Kong
62021038254.0	Synthetic Chimeric Vaccinia Virus	Hong Kong
PI 2024003859	Synthetic Chimeric Vaccinia Virus	Malaysia
810669	Synthetic Chimeric Vaccinia Virus	New Zealand

Poxvirus vaccine against COVID-19

Application No.	Title	Country / Region
17/187,678	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	U.S.A.
110107179	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Taiwan
114138879	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Taiwan
20210100512	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Argentina
1202200348	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	African Intellectual Property Organization
AP/P/2022/014318	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	African Regional Intellectual Property Organization
2021226592	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Australia
BR112022016992-2	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Brazil
3173996	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Canada
202180027983.6	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	China
202292431	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Eurasian Patent Office
21715007.7	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	European Patent Office
202217053476	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	India
P00202210244	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Indonesia
295925	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Israel
2022-551297	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Japan
2026-0034131	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Japan
PI 2022004613	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Malaysia
MX/a/2022/010588	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Mexico
791924	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	New Zealand
830553	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	New Zealand
10-2022-7033014	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Republic of Korea
522440323	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Saudi Arabia
2022/09895	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	South Africa
523451920	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Saudi Arabia
62023075022.1	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Hong Kong
62023083678.0	Recombinant Poxvirus Based Vaccine against SARS-CoV-2 virus	Hong Kong

TFF2 therapeutics

Application No.	Title	Country / Region
17/638,761	Modified TFF2 polypeptides	U.S.A.
2020338947	Modified TFF2 polypeptides	Australia
3152665	Modified TFF2 polypeptides	Canada
202080071768.1	Modified TFF2 polypeptides	China
20781063.1	Modified TFF2 polypeptides	European Patent Office
202217016249	Modified TFF2 polypeptides	India
290910	Modified TFF2 polypeptides Containing Compositions and Methods of Use Thereof	Israel
2022-513154	Modified TFF2 polypeptides	Japan
2025-86620	Modified TFF2 polypeptides	Japan
MX/a/2022/002337	Modified TFF2 polypeptides	Mexico
786004	Modified TFF2 polypeptides	New Zealand
824645	Modified TFF2 polypeptides	New Zealand
2022/03355	Modified TFF2 polypeptides	South Africa
62023066535.3	Modified TFF2 polypeptides	Hong Kong
62023066928.0	Modified TFF2 polypeptides	Hong Kong

Antiviral Drugs – Cathepsin Inhibitors

Application No.	Title	Country / Region
18/055,596	Compositions and Methods for Increasing Efficacy of a Drug	U.S.A.
2022-569505	Compositions and Methods for Increasing Efficacy of a Drug	Japan
202217072271	Compositions and Methods for Increasing Efficacy of a Drug	India
62023079383.3	Compositions and Methods for Increasing Efficacy of a Drug	Hong Kong

Triptan Compound – Formulations

Application No.		Title		Country / Region
18/782,922		Formulations Comprising Triptan Compounds		U.S.A.

Triptan Compound – Migraine

Application No.	Title	Country / Region
18/797,812	Methods of Treating Migraine	U.S.A.
18/783,734	Pharmaceutical Composition for Treating Migraine	U.S.A.

Tianeptine – Conditions Associated with Peroxisome Proliferator-Activated Receptor

Application No.	Title	Country / Region
PCT/US2024/021799	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	PCT
19/469,537	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	U.S.A.
2024245246	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	Australia
BR112025020808-0	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	Brazil
3287412	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	Canada
202480032955.7	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	China
24719842.7	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	European Patent Office
323504	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	Israel
202517102234	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	India
2025-556587	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	Japan
PI 2025005867	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	Malaysia
MX/a/2025/011371	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	Mexico
826013	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	New Zealand
1120257039	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	Saudi Arabia
11202506430U	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	Singapore
2025/08940	(S)-Tianeptine and Use in Treating Disorders and Conditions Associated with Peroxisome Proliferator-Activated Receptor	South Africa

Trademarks and Service Marks

Tonix Pharmaceuticals, Inc.

We seek trademark and service mark protection in the United States and outside of the United States where available and when appropriate. We are the owner of the following U.S. federally registered mark: TONIX PHARMACEUTICALS (Reg. No. 4656463, issued December 16, 2014).

56 We are the owner of the following marks for which applications for U.S. federal registration are currently pending: FYMRALIN (Serial No. 98/327953, filed December 22, 2023), MODALTIN (Serial No. 99/562722, filed December 23, 2025), RAPONTIS (Serial No. 90/562733, filed December 23, 2025), PROTECTIC (Serial No. 99/562746, filed December 23, 2025), TONIX PHARMACEUTICALS (Serial No. 98/577945, filed May 31, 2024), ANGSTRO-TECHNOLOGY (Serial No. 98/006538, filed May 22, 2023) ).

We are the owner of the following marks for which applications for U.S. federal registration are currently pending: FYMRALIN (Serial No. 98/327953, filed December 22, 2023), MODALTIN (Serial No. 97/424052, filed May 23, 2022), RAPONTIS (Serial No. 97/424058, filed May 23, 2022), PROTECTIC (Serial No. 97/424071, filed May 23, 2022), TONIX PHARMACEUTICALS (Serial No. 98/577945, filed May 31, 2024), ANGSTRO-TECHNOLOGY (Serial No. 98/006538, filed May 22, 2023) and TNX-102 SL (Serial No. 97/185424, filed December 22, 2021).

Tonix Medicines, Inc.

We ~~seek trademark and service mark protection in the United States~~ ~~and outside of the United States where available and when appropriate. We~~ are the owner of the following U.S. federally registered marks: NOTIME4MIGRAINES (Reg. No. 5392512, issued January 30, 2018); SYMTOUCH (Reg. No. 5186988, issued April 18, 2017); TOSYMRA (Reg. No. 5981221, issued February 11, 2020); TOSYMRA & DROPLET Design (Reg. No. ~~6142333~~6124333, issued August 11, 2020); ZEMBRACE (Reg. No. 5186989, issued April 18, 2017); ZEMBRACE SYMTOUCH (Reg. No.5478282, issued May 29, 2018); DROPLET Design (Reg. No. 6117797, issued August 4, 2020); TONIX ONE LOGO Design (Serial No. 99/057051, filed February 26, 2025). We are the owner of the following International Registrations under the Madrid Protocol: TOSYMRA (Reg. No. 1501060, issued October 16, 2019 – Extensions of Protection to: Canada, European Union, Japan, ~~Republic~~ Republic of Korea~~, United Kingdom~~); ZEMBRACE (Reg. No. 1683288, issued August 17, 2022 – Extensions of Protection to: Canada ~~(still pending)~~, China, European Union, Israel, Mexico, United Kingdom); DROPLET Design (Reg. No. 1545038, issued June 29, 2020 – Extensions of Protection to: Canada, European Union, Israel, Japan, Norway, Republic of Korea, Switzerland, Turkey, United Kingdom); European Union: TONIX ONE LOGO Design (~~Application~~Registration No. ~~19151272~~019151272, ~~filed~~issued ~~March~~July 49, 2025); United Kingdom: TOSYMRA, Reg. No. UK00801501060.

Tonix Pharma Limited

We are the owner of the mark TONMYA for which U.S. Application Serial Number: 97/185424, filed December 22, 2021, is currently pending.

Research and Development

We have approximately 45 70 employees dedicated to research and development. Our research and development operations are located in Berkeley ~~Chatham~~Heights, NJ, Frederick, Maryland, Dublin, Ireland and Montreal, Canada. We have used, and expect to continue to use, third parties to conduct our nonclinical and clinical studies.

Marketing

We have nine employees supporting sales administration and marketing initiatives. We also have three sales employees who are focused on customer service requests and top-tier headache specialists. We utilize third party vendors to support trade, managed markets, marketing initiatives, and promotional compliance programs.

Manufacturing

We have contracted with third-party cGMP-compliant contract manufacturer organizations(“CMOs”), for the manufacture of TNX-102 SL drug substance and drug products for clinical and commercial supply. Our manufacturing operations are managed and controlled out of our Dublin, Ireland offices.

All of our small molecules drug candidates are synthesized using industry standard processes, and our drug products are formulated using commercially available pharmaceutical grade excipients.

We own a 45,000 square foot facility in Massachusetts, to house our new Advanced Development Center for accelerated development and manufacturing of vaccines and biologics. This facility is currently decommissioned. It was designed for the manufacture of nonclinical and clinical investigational products for our Infectious Disease portfolio. The current focus of which is TNX-801 a Smallpox and Mpox Preventing Vaccine ~~and TNX-1800 a COVID vaccine selected by NIH/NIAID Project NextGen for Inclusion in Clinical Trials~~. This facility was decommissioned in 2024 but ~~Tonix~~may ~~has~~be reactivated the earlier ~~ability~~of to2027 ~~reactivate~~or itin ~~should~~the wecase ~~choose~~of ~~to do~~a sonational or international emergency.

57 Our other marketed products, Zembrace and Tosymra, are manufactured at cGMP compliant, FDA audited, U.S. based CMOs with expertise in pre-filled syringe and inhalation expertise.

Our two marketed products, Zembrace and Tosymra, are manufactured at cGMP compliant, FDA audited, U.S. based CMOs with expertise in pre-filled syringe and inhalation expertise.

Government Regulations

~~The~~Government authorities ~~FDA~~in ~~and~~the ~~other~~United ~~federal~~States, ~~state,~~ ~~local~~at ~~and foreign regulatory agencies impose substantial requirements upon~~ the ~~clinical development~~federal, ~~approval,~~state ~~labeling, manufacture, marketing~~ and ~~distribution~~local oflevel, ~~drug~~and ~~products.~~other ~~These~~countries ~~agencies~~extensively regulate, among other things, the research, ~~and~~ development ~~activities~~, ~~and the~~ testing, ~~approval,~~ manufacture, quality control, ~~safety~~approval, ~~effectiveness~~labeling, ~~labeling~~packaging, storage, record -keeping, ~~advertising and~~ promotion ~~of our product candidates. The regulatory approval process is generally lengthy and expensive~~, ~~with no guarantee~~ ~~of a positive result. Moreover~~advertising, ~~failure to comply with applicable requirements by the FDA or other requirements may result in civil or criminal penalties~~distribution, ~~recall~~post-approval ormonitoring ~~seizure~~and ~~of products~~reporting, ~~injunctive~~marketing ~~relief~~and ~~including~~export ~~partial~~and orimport ~~total suspension~~ of ~~production,~~products ~~or withdrawal~~such ofas athose ~~product~~we ~~from~~are ~~the market~~developing.

~~The FDA regulates, among other things, the research, manufacture, promotion and distribution of drugs in the~~ U.S. ~~under the FDCA and other statutes~~ ~~and~~Government ~~implementing regulations. The process required by the FDA before prescription drug product candidates may be marketed in the U.S. generally involves the following:~~Regulation

●In the ~~completion~~United ofStates, ~~extensive~~the ~~nonclinical~~FDA ~~laboratory~~regulates ~~tests~~drugs under the Federal Food, ~~animal~~Drug, ~~studies~~and Cosmetic Act, or FDCA, and ~~formulation~~its ~~studies~~implementing regulations, and ~~all~~biologics ~~performed~~under the FDCA and the Public Health Service Act, or PHSA, and its implementing regulations. FDA approval is required before any new unapproved drug or dosage form, including a new use of a previously approved drug, can be marketed in ~~accordance~~the United States. Drugs and biologics are also subject to other federal, state and local statutes and regulations. If we fail to comply with applicable FDA or other requirements at any time during the drug development process, clinical testing, the approval process or after approval, we may become subject to administrative or judicial sanctions. These sanctions could include the FDA’s ~~Good~~refusal ~~Laboratory~~to ~~Practice~~approve ~~regulations;~~pending applications, license suspension or revocation, withdrawal of an approval, warning letters, product recalls, product seizures, placement on Import Alerts, debarment of personnel, employees or officers, total or partial suspension of production or distribution, injunctions, fines, civil penalties or criminal prosecution.

●The process ~~submission~~required toby the FDA ofbefore anproduct ~~IND,~~candidates ~~which~~may ~~must~~be ~~become~~marketed ~~effective~~in ~~before~~the ~~human~~United ~~clinical~~States ~~trials~~generally ~~may~~involves ~~begin;~~the following:

● ~~performance~~completion of ~~adequate~~extensive ~~and~~preclinical ~~well-controlled~~laboratory ~~human~~tests, ~~clinical~~preclinical ~~trials~~animal ~~in accordance with the FDA’s regulations~~studies, ~~including~~and ~~Good~~toxicity ~~Clinical Practices~~data, toall ~~establish~~performed ~~the~~in ~~safety~~accordance ~~and~~with ~~efficacy of~~ the ~~product~~good ~~candidate~~laboratory ~~for~~practices, ~~each~~or ~~proposed~~GLP, ~~indication~~regulations;

● submission to the FDA of an ~~NDA for drug products~~IND, orwhich amust ~~Biologics~~become ~~License~~effective ~~Application,~~before orhuman ~~BLA,~~clinical ~~for~~studies ~~biologic~~may ~~products~~begin;

● ~~satisfactory~~approval ~~completion of a preapproval inspection~~ by ~~the~~an ~~FDA~~independent ofIRB ~~the~~or ~~manufacturing~~ethics ~~facilities~~committee atrepresenting ~~which~~each ~~the~~clinical ~~product~~site isbefore ~~produced~~each toclinical ~~assess~~study ~~compliance~~may ~~with~~be ~~cGMP regulations~~initiated; ~~and~~

● ~~the~~performance ~~FDA’s~~of ~~review~~adequate and ~~approval~~well-controlled ofhuman clinical studies to establish the ~~NDA~~safety and efficacy, or ~~BLA~~in ~~prior~~the tocase ~~any~~of ~~commercial~~a ~~marketing~~biologic, ~~sale~~the orsafety, ~~shipment~~purity and potency, of the drug. candidate for each proposed indication;

~~The~~● ~~testing~~preparation of and ~~approval process~~submission ~~requires~~to ~~substantial~~the ~~time~~FDA of a new drug application, ~~effort~~or ~~and~~NDA, ~~financial~~or ~~resources~~biologics license application, or BLA, which must include data from required pre-clinical studies and weall ~~cannot~~pivotal beclinical ~~certain~~studies ~~that~~and ~~any~~information ~~approvals~~showing ~~for~~that ~~our~~the product ~~candidates~~ ~~will~~can be ~~granted~~manufactured onin a ~~timely~~controlled ~~basis, if at all.~~manner;

~~Nonclinical~~● ~~tests~~a ~~include laboratory~~determination evaluations of product chemistry, formulation and stability, as well as studies to evaluate toxicity in animals and other animal studies. The results of nonclinical tests, together with manufacturing information and analytical data, are submitted as part of an IND to the FDA. Some nonclinical testing may continue even after an IND is submitted. The IND also includes one or more protocols for the initial clinical trial or trials and an investigator’s brochure. An IND automatically becomes effective 30 days after receipt by the FDA, ~~unless the FDA,~~ within ~~the~~60 ~~30-day~~days ~~time~~of ~~period,~~its ~~raises~~receipt ~~concerns~~of oran ~~questions~~NDA ~~relating to the proposed clinical trials as outlined in the IND and places the clinical trial on a clinical hold. In such cases, the IND sponsor and the FDA must resolve any outstanding concerns~~ or ~~questions~~BLA ~~before any clinical trials can begin. Clinical trial holds also may be imposed at any time before or during studies due~~ to ~~safety~~file ~~concerns or non-compliance with regulatory requirements. An independent Institutional Review Board, or IRB, at each of~~ the ~~clinical~~application ~~centers proposing to conduct the clinical trial must review and approve the plan~~ for any clinical trial before it commences at that center. An IRB considers, among other things, whether the risks to individuals participating in the trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves the consent form signed by the trial participants and must monitor the study until completed.review;

58 ● review of the product application by an FDA advisory committee, where appropriate and if applicable;

~~Clinical Trials~~ 48

~~Clinical~~● ~~trials~~satisfactory ~~involve the~~completion ~~administration~~ of ~~the~~an ~~product~~FDA ~~candidate~~pre-approval toinspection ~~human subjects under the supervision~~ of ~~qualified medical investigators according to approved protocols that detail~~ the ~~objectives~~manufacturing offacilities ~~the~~where ~~study, dosing procedures, subject selection and exclusion criteria, and~~ the ~~parameters~~drug tocandidate ~~be used to monitor participant safety. Each protocol for a U.S. study~~ is ~~submitted~~produced to ~~the~~assess ~~FDA~~compliance aswith ~~part~~cGMP; ~~of the IND.~~and

~~Human~~● ~~clinical~~FDA ~~trials are~~review ~~typically~~and ~~conducted~~approval inof ~~three~~an ~~sequential~~NDA ~~phases,~~or ~~but~~BLA ~~the~~prior ~~phases~~to ~~may~~any ~~overlap,~~commercial marketing or besale ~~combined~~of the drug or biologic.

●An IND ~~Phase~~is 1a ~~clinical~~request ~~trials~~for ~~typically~~authorization ~~involve~~from the ~~initial~~FDA ~~introduction~~to administer an investigational new drug product to humans. The central focus of an IND submission is on the ~~product~~general ~~candidate~~investigational ~~into~~plan ~~healthy~~and the protocol(s) for human ~~volunteers~~studies. InThe ~~Phase~~IND 1also ~~clinical~~includes ~~trials~~results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology and pharmacodynamic characteristics of the product; ~~candidate~~chemistry, manufacturing isand ~~typically~~controls ~~tested~~information; ~~for~~and ~~safety,~~any ~~dosage~~available ~~tolerance,~~human ~~absorption,~~data ~~metabolism~~or literature to support the use of the investigational new drug. An IND must become effective before human clinical studies may begin. An IND will automatically become effective 30 days after receipt by the FDA, ~~distribution~~unless before that time the FDA raises concerns or questions related to the proposed clinical studies. In such a case, ~~excretion~~the IND may be placed on clinical hold and ~~pharmacodynamics~~the IND sponsor and the FDA must resolve any outstanding concerns or questions before clinical studies can begin. Accordingly, submission of an IND may or may not result in the FDA allowing clinical studies to commence.

● Phase 2 clinical trials are generally conducted in a limited patient population to gather evidence about the efficacy of the product candidate for specific, targeted indications; to determine dosage tolerance and optimal dosage; and to identify possible adverse effects and safety risks. Phase 2 clinical trials, in particular Phase 2b trials, can be undertaken to evaluate clinical efficacy and to test for safety in an expanded patient population at geographically dispersed clinical trial sites.Clinical Studies

●Clinical studies ~~Phase~~involve 3the ~~clinical~~administration ~~trials~~of ~~are~~the ~~undertaken~~investigational new drug to ~~evaluate~~human ~~clinical~~subjects ~~efficacy~~under ~~and~~the tosupervision ~~test~~of qualified investigators in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for ~~safety~~their participation in anany ~~expanded~~clinical ~~patient~~study. ~~population~~Clinical atstudies ~~geographically~~are ~~dispersed~~conducted ~~clinical~~under ~~trial~~protocols ~~sites.~~detailing, ~~The~~among ~~size~~other things, the objectives of ~~Phase~~the 3study, ~~clinical~~and the ~~trials~~parameters ~~depends~~to ~~upon~~be ~~clinical~~used in monitoring safety and ~~statistical~~the ~~considerations~~efficacy criteria to be evaluated. A protocol for ~~the~~each ~~product~~clinical ~~candidate~~study and ~~disease~~any subsequent protocol amendments must be submitted to the FDA as part of the IND. ~~Phase~~Additionally, 3approval must also be obtained from each clinical ~~trials~~study ~~are~~site’s ~~intended~~IRB tobefore ~~establish~~the studies may be initiated, and the ~~overall~~IRB ~~risk-benefit~~must ~~ratio~~monitor ofthe study until completed. There are also requirements governing the ~~product~~reporting ~~candidate~~of ongoing clinical studies and ~~provide~~clinical anstudy ~~adequate~~results ~~basis~~to ~~for~~public ~~product~~registries, ~~labeling~~such as ClinicalTrials.gov.

~~Post-approval clinical~~The ~~trials,~~clinical ~~sometimes~~investigation ~~referred~~of toa asdrug ~~Phase~~or 4biologic ~~clinical~~is ~~trials,~~generally ~~may~~divided beinto ~~conducted~~three ~~after~~or ~~initial~~four ~~approval~~phases. ~~These~~Although ~~clinical~~the ~~trials~~phases are ~~used~~usually conducted tosequentially, ~~gain~~they ~~additional~~may ~~experience~~overlap ~~from~~or ~~the~~be ~~treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up~~combined.

~~Clinical~~● ~~testing~~Phase ~~must satisfy the extensive regulations of the FDA~~1. ~~Reports~~The ~~detailing~~drug ~~the~~or ~~results~~biologic ofis ~~the~~initially ~~clinical~~introduced ~~trials~~into ~~must~~healthy behuman ~~submitted~~subjects ator ~~least~~patients ~~annually to~~with the ~~FDA~~target ~~and~~disease ~~safety~~or ~~reports must be submitted for serious and unexpected adverse events~~condition. ~~Success~~These instudies ~~early-stage~~are ~~clinical~~designed ~~trials does~~to ~~not~~evaluate ~~assure~~the ~~success~~safety, indosage ~~later-stage clinical trials. The FDA~~tolerance, anmetabolism ~~IRB~~and orpharmacologic weactions ~~may~~of ~~suspend~~the ainvestigational ~~clinical~~new ~~trial~~drug atin ~~any time on various grounds~~humans, ~~including~~the aside ~~finding~~effects ~~that~~associated ~~the~~with ~~research~~increasing ~~subjects~~doses, orand ~~patients~~if ~~are~~possible, ~~being exposed~~ to angain ~~unacceptable~~early ~~health~~evidence ~~risk~~on effectiveness.

~~New~~● ~~Drug~~Phase ~~Applications~~2. The drug or biologic is administered to a limited patient population to evaluate dosage tolerance and optimal dosage, identify possible adverse side effects and safety risks and preliminarily evaluate efficacy.

~~Assuming~~● ~~successful completion~~Phase of3. ~~the~~The ~~required~~drug ~~clinical~~or ~~trials,~~biologic ~~the~~is ~~results~~administered ~~of product development, nonclinical studies and clinical trials are submitted~~ to ~~the FDA as part of~~ an ~~NDA~~expanded ~~(or~~patient ~~BLA~~population, ingenerally ~~the~~at ~~case~~geographically ofdispersed aclinical ~~biologic~~study ~~product).~~sites Anto ~~NDA~~generate orenough ~~BLA~~data ~~also~~to ~~must~~statistically ~~contain~~evaluate ~~extensive manufacturing information~~dosage, asclinical ~~well~~effectiveness ~~as proposed labeling for the finished product. An NDA or BLA applicant must develop information about the chemistry~~ and ~~physical~~safety, ~~characteristics~~to ofestablish the ~~drug~~overall ~~and~~benefit-risk ~~finalize~~relationship ~~a process for manufacturing the product in accordance with cGMP. The manufacturing process must be capable~~ of ~~consistently producing quality product within specifications approved by~~ the ~~FDA. The~~investigational ~~manufacturer must develop methods for testing the quality, purity and potency of the final~~ product. ~~In addition, appropriate packaging must be selected~~ and ~~tested, and stability studies must be conducted~~ to ~~demonstrate~~provide ~~that the product does not undergo unacceptable deterioration over its shelf life. Prior to approval, the FDA will conduct~~ an ~~inspection~~adequate ofbasis ~~the~~for ~~manufacturing~~product ~~facilities to assess compliance with cGMP~~approval.

~~The~~● ~~FDA~~Phase ~~reviews~~4. ~~all NDAs~~In ~~and~~some ~~BLAs~~cases, ~~submitted~~the ~~before it accepts them for filing. The~~ FDA may ~~request~~condition ~~additional~~approval ~~information~~of ~~rather than accept~~ an NDA ~~for~~ ~~filing. In this event, the NDA~~ or BLA ~~must~~for bea ~~resubmitted~~drug ~~with~~candidate on the ~~additional~~sponsor’s ~~information~~agreement ~~and is subject~~ to ~~review~~conduct ~~before~~additional ~~the FDA~~clinical ~~accepts~~studies itafter ~~for filing~~approval. ~~After~~In another ~~application is filed~~cases, ~~the~~a ~~FDA~~sponsor may ~~refer~~commit ~~the~~to ~~NDA~~conducting or ~~BLA~~voluntarily toconduct anadditional ~~advisory~~clinical ~~committee~~studies ~~for~~after ~~review, evaluation~~approval ~~and recommendation as~~ to ~~whether~~gain ~~the~~more ~~application~~information ~~should~~about ~~be approved and under what conditions. The FDA is not bound by~~ the ~~recommendations of an advisory committee, but it considers them carefully when making decisions~~drug. ~~The~~Such ~~FDA may deny~~ post-approval of anstudies ~~NDA or BLA if the applicable regulatory criteria~~ are ~~not~~typically ~~satisfied.~~referred ~~Data~~to ~~obtained~~as ~~from~~Phase 4 clinical ~~trials are not always conclusive and the FDA may interpret data differently than we interpret the same data~~studies.

59 A confirmatory or pivotal study is a clinical study that adequately meets regulatory agency requirements for the evaluation of a drug candidate’s efficacy and safety such that it can be used to justify the approval of the product. Generally, pivotal studies are Phase 3 studies, but the FDA may accept results from Phase 2 studies if the study design provides a well-controlled and reliable assessment of clinical benefit, particularly in situations where there is an unmet medical need and the results are sufficiently robust. In such cases, FDA may require post-market studies for safety and efficacy to be conducted for the drug candidate. The FDA may withdraw the approval if the results indicate that the approved drug is not safe or effective.

The ~~FDA may issue a~~ ~~complete response letter~~FDA, ~~which~~the ~~may~~IRB ~~require~~or ~~additional~~the clinical orstudy ~~other~~sponsor ~~data~~may suspend or ~~impose~~terminate ~~other~~a ~~conditions~~clinical ~~that~~study ~~must~~at beany ~~met~~time inon ~~order to~~various ~~secure~~grounds, ~~final~~including ~~approval of the NDA or BLA. If~~ a ~~product~~finding that ~~receives regulatory approval,~~ the ~~approval~~research ~~may~~subjects beare ~~significantly~~being ~~limited~~ exposed to ~~specific~~an ~~diseases~~unacceptable ~~and~~health ~~dosages~~risk. orAdditionally, ~~the~~some ~~indications~~clinical ~~for~~studies ~~use~~are ~~may~~overseen ~~otherwise~~by bean ~~limited,~~independent group ~~which~~of ~~could~~qualified ~~restrict~~experts ~~the~~organized ~~commercial~~by ~~value of~~ the ~~product.~~clinical Instudy ~~addition~~sponsor, ~~the~~known ~~FDA~~as ~~may~~a ~~require~~data ussafety tomonitoring ~~conduct~~board ~~Phase~~or 4committee. ~~testing~~This ~~which~~group provides ~~involves~~authorization ~~clinical~~for ~~trials~~whether ~~designed~~or tonot ~~further assess~~ a ~~drug’s~~study ~~safety~~may ~~and~~move ~~effectiveness~~forward ~~after~~at ~~NDA~~designated orcheck ~~BLA~~points ~~approval,~~based ~~and~~on ~~may~~access ~~require~~to ~~surveillance~~certain ~~programs~~data tofrom ~~monitor~~ the ~~safety of approved products which have been commercialized~~study. ~~Once~~We ~~issued, the FDA~~ may ~~withdraw~~also ~~product~~suspend ~~approval~~or ifterminate ~~ongoing~~a ~~regulatory requirements~~clinical ~~are~~study ~~not~~based ~~met~~on orevolving ifbusiness ~~safety~~objectives and/or ~~efficacy~~competitive ~~questions are raised after the product reaches the market~~climate.

~~Section 505(b) NDAs~~49

~~There are two types of NDAs: the Section 505(b)(1) NDA~~Chemistry, ~~or full NDA, and~~ ~~the~~Manufacturing ~~Section 505(b)(2) NDA. A full NDA is submitted under Section 505(b)(1) of the FDCA,~~ and ~~must~~Control contain full reports of investigations conducted by the applicant to demonstrate the safety and effectiveness of the drug. A Section 505(b)(2) NDA may be submitted for a drug for which one or more of the investigations relied upon by the applicant was not conducted by or for the applicant and for which the applicant has no right of reference from the person by or for whom the investigations were conducted. A Section 505(b)(2) NDA may be submitted based in whole or in part on published literature or on the FDA’s finding of safety and efficacy of one or more previously approved drugs, which are known as reference drugs. Thus, the filing of a Section 505(b)(2) NDA may result in approval of a drug based on fewer clinical or nonclinical studies than would be required under a full NDA. The number and size of studies that need to be conducted by the sponsor depends on the amount and quality of data pertaining to the reference drug that are publicly available, and on the similarity of and differences between the applicant’s drug and the reference drug. In some cases, extensive, time-consuming, and costly clinical and nonclinical studies may still be required for approval of a Section 505(b)(2) NDA.Information

~~Our~~Companies seeking ~~drug~~FDA approval ~~strategy~~of ~~for~~drugs ~~our~~must ~~new~~also ~~formulations~~develop ofdata ~~approved~~and ~~chemical entities~~information isabout tothe ~~submit~~physical ~~Section~~characteristics ~~505(b)(2)~~of ~~NDAs to~~ the ~~FDA.~~components Weof ~~submitted~~a ~~NDA~~product as ~~under~~well ~~Section~~as ~~505(b)(2)~~finalize ~~for~~processes ~~TNX-102 SL~~ for ~~FM,~~manufacturing ~~and~~the ~~plan~~components toin ~~submit an~~commercial ~~505(b)(2)for~~quantities ~~TNX-2900~~in ~~for~~accordance ~~Prader~~with ~~Willi~~GMP ~~Syndrome~~requirements. The manufacturing ~~FDA~~process ~~may~~must ~~not~~be ~~agree~~capable ~~that~~of ~~these~~consistently ~~product~~producing ~~candidates~~quality ~~are~~batches ~~approvable~~of ~~as a Section 505(b)(2) NDA. If~~ the ~~FDA~~product ~~determines~~candidate ~~that a Section 505(b)(2) NDA is not appropriate~~ and, ~~that~~among aother ~~full NDA is required~~things, the sponsor ~~time~~must ~~and~~develop ~~financial~~methods ~~resources required~~for totesting ~~obtain~~the ~~FDA~~identity, ~~approval~~strength, ~~could~~quality, ~~substantially~~potency and ~~materially~~purity ~~increase~~of ~~and~~the befinal ~~less likely to be approved~~product. IfAdditionally, ~~the FDA requires a full~~appropriate ~~NDA~~packaging ormust ~~requires~~be ~~more~~selected ~~extensive~~and ~~testing~~tested, and ~~development~~stability ~~for~~studies ~~some~~must ~~other~~be ~~reason,~~conducted ~~our ability~~ to ~~compete~~demonstrate ~~with alternative products~~ that ~~arrive on~~ the ~~market~~components ~~more~~of ~~quickly~~a ~~than our~~ product ~~candidates would be adversely impacted. If reference listed products are withdrawn from the~~candidate ~~market~~do ~~by the FDA for a safety reason, we may~~ not beundergo ~~able~~unacceptable todeterioration ~~reference~~over ~~such~~their ~~products~~shelf ~~to support our anticipated 505(b)(2) NDAs, and we may be required to follow the requirements of Section 505(b)(1)~~life.

~~Patent~~Submission of ~~Protections~~an NDA or BLA to the FDA

~~An applicant submitting~~Assuming asuccessful ~~Section~~completion ~~505(b)(2)~~of ~~NDA~~all ~~must~~required ~~certify~~testing toin ~~the~~accordance ~~FDA~~ with ~~respect~~all toapplicable ~~the~~regulatory ~~patent~~requirements, ~~status~~detailed ofinvestigational ~~the reference~~ new drug ~~upon~~product ~~which~~information ~~the~~is ~~applicant relies~~submitted ~~in support of approval of its drug. With respect~~ to ~~every patent listed in~~ the FDA’s ~~Orange~~in ~~Book, which is~~ the ~~FDA’s list~~form of ~~approved~~an ~~drug~~NDA ~~products, as claiming the reference drug~~ or anBLA ~~approved~~requesting ~~method~~approval ofto ~~use~~market of the ~~reference~~product ~~drug, the Section 505(b)(2) applicant must certify that: (1) there is no patent information listed in the orange book~~ for ~~the~~one ~~reference~~or ~~drug; (2)~~more ~~the~~indications. ~~listed~~Under ~~patent~~federal ~~has expired; (3) the listed patent has not expired~~law, ~~but will expire on a particular date; (4)~~ the ~~listed~~submission ~~patent is invalid or will not be infringed by the manufacture, use, or sale~~ of ~~the~~most ~~product~~NDAs inand ~~the~~BLAs ~~Section 505(b)(2) NDA; or (5) if the patent~~ is asubject ~~use~~to ~~patent, that the applicant does not seek approval for~~ a ~~use~~substantial ~~claimed~~application byuser ~~the patent~~fee. IfApplications ~~the applicant files a certification~~for toorphan ~~the~~drug ~~effect~~products of clause (1), (2) or (5), FDA approval of the Section 505(b)(2) NDA may be made effective immediately upon successful FDA review of the application, in the absence of marketing exclusivity delays, which are ~~discussed~~exempted ~~below.~~from If the ~~applicant files a certification to the effect of clause (3), the Section 505(b)(2)~~ NDA ~~approval may not be made effective until the expiration of the relevant patent~~ and ~~the~~BLA ~~expiration~~application ofuser ~~any marketing exclusivity delays~~fees.

60 An NDA or BLA must include all relevant data available from pertinent preclinical and clinical studies, including negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls and proposed labeling, among other things. Data can come from company-sponsored clinical studies intended to test the safety and effectiveness of a use of a product, or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and effectiveness of the investigational product to the satisfaction of the FDA.

~~If the Section 505(b)(2)~~Once an NDA ~~applicant~~or ~~provides~~BLA ahas ~~certification~~been ~~to the effect of clause (4)~~submitted, ~~referred to as a paragraph IV certification,~~ the ~~applicant also~~FDA’s ~~must~~goal ~~send~~is ~~notice of the certification~~ to ~~the~~review ~~patent owner and~~ the ~~holder~~application ~~of the NDA for the reference drug. The filing of a patent infringement lawsuit~~ within 45ten ~~days~~months ofafter ~~the~~it ~~receipt~~accepts of the ~~notification may prevent the FDA from approving the Section~~application ~~505(b)(2) NDA~~ for 30filing, ~~months~~or, ~~from~~if the ~~date~~application ofrelates ~~the~~to ~~receipt~~an ofunmet ~~the~~medical ~~notification~~need ~~unless~~in ~~the court determines that~~ a ~~longer~~serious or ~~shorter period~~life-threatening isindication, ~~appropriate~~six ~~because~~months ~~either~~after ~~party to~~ the ~~action failed to reasonably cooperate in expediting the action. However, the~~ FDA ~~may~~accepts ~~approve~~ the ~~Section~~application ~~505(b)(2)~~for ~~NDA~~filing. ~~before~~The ~~the~~review 30process ~~months~~is ~~have~~often ~~expired~~significantly ifextended aby ~~court~~FDA ~~decides~~requests ~~that~~for ~~the~~additional ~~patent is invalid or not~~information ~~infringed,~~ or ~~if a court enters a settlement order or consent decree stating the patent is invalid or not infringed~~clarification.

~~Notwithstanding~~Before ~~the~~approving ~~approval~~an ofNDA ~~many~~or ~~products~~BLA, by the FDA ~~pursuant~~typically towill ~~Section~~inspect ~~505(b)(2), over~~ the ~~last~~facility ~~few~~or ~~years~~facilities ~~certain~~where ~~brand-name pharmaceutical companies and others have objected to~~ the ~~FDA’s~~product ~~interpretation~~is ~~of Section 505(b)(2)~~manufactured. IfThe ~~the~~ FDA’s ~~interpretation~~will ofnot ~~Section~~approve ~~505(b)(2)~~an isapplication ~~successfully~~unless ~~challenged~~it indetermines ~~court,~~that the ~~FDA~~manufacturing ~~may~~processes beand ~~required~~facilities toare ~~change~~in ~~its~~compliance ~~interpretation~~with ofcGMP ~~Section 505(b)(2)~~requirements ~~which could delay or even prevent the FDA from approving any Section 505(b)(2) NDA that we submit. The pharmaceutical industry is highly competitive,~~ and itadequate isto ~~not~~assure ~~uncommon~~consistent ~~for~~production ~~a manufacturer~~ of anthe ~~approved~~ product towithin ~~file~~required ~~a citizen petition with the FDA seeking to delay approval of, or impose additional approval requirements for, pending competing products~~specifications. ~~If successful~~Additionally, ~~such~~before ~~petitions can~~approving ~~significantly~~an ~~delay,~~NDA or ~~even prevent~~ BLA, the ~~approval of the new product. Moreover, even if the~~ FDA ~~ultimately~~will ~~denies~~typically ~~such~~inspect aone ~~petition, the~~or ~~FDA~~more ~~may~~clinical ~~substantially~~sites ~~delay~~to ~~approval~~assure ~~while~~compliance itwith ~~considers and responds to the petition~~GCP.

~~Marketing~~The FDA ~~Exclusivity~~is required to refer an application for an investigational drug or biologic to an advisory committee or explain why such referral was not made. An advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to whether the investigational product application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions and typically follows such recommendations.

~~Market exclusivity provisions under the FDCA can delay the submission or the approval of Section 505(b)(2) NDAs, thereby delaying a Section 505(b)(2) product from entering the market.~~ The ~~FDCA provides five-year marketing exclusivity to the first applicant to gain approval of~~ anFDA’s ~~NDA~~Decision ~~for~~on an ~~NCE, meaning that the FDA has not previously approved any other drug containing the same active moiety. This exclusivity prohibits the submission of a Section 505(b)(2)~~ NDA for any drug product containing the active ingredient during the five-year exclusivity period. However, submission of a Section 505(b)(2) NDA that certifies that a listed patent is invalid, unenforceable, or will not be infringed, as discussed above, is permitted after four years, but if a patent infringement lawsuit is brought within 45 days after such certification, FDA approval of the Section 505(b)(2) NDA may automatically be stayed until 7½ years after the NCE approval date. The FDCA also provides three years of marketing exclusivity for the approval of new and supplemental NDAs for product changes, including, among other things, new indications, dosage forms, routes of administration or strengths of an existing drug, or for a new use, if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by FDA to be essential to the approval of the application.BLA

~~Five-year~~After the FDA evaluates the NDA or BLA and ~~three-year exclusivity~~conducts ~~will~~inspections ~~not~~of ~~delay~~manufacturing ~~the~~facilities, ~~submission~~it may issue an approval letter or a Complete Response Letter. An approval letter authorizes commercial marketing of ~~another~~the ~~full~~drug ~~NDA;~~or ~~however,~~biologic aswith ~~discussed~~specific ~~above~~prescribing information for specific indications. A Complete Response Letter indicates that the review cycle of the application is complete, anand ~~applicant~~the ~~submitting~~application ais ~~full~~not ~~NDA~~ready ~~under~~for ~~Section~~approval. ~~505~~A Complete Response Letter may require additional clinical data and/or an additional pivotal Phase 3 clinical study(bies)~~(1)~~, ~~would~~and/or beother ~~required~~significant, expensive and time-consuming requirements related to ~~conduct~~clinical studies, preclinical studies or ~~obtain~~manufacturing. Even if such additional information is submitted, the FDA may ultimately decide that the NDA or BLA does not satisfy the criteria for approval. The FDA could also approve the NDA or BLA with a ~~right~~REMS ofto ~~reference~~mitigate risks, which could include medication guides, physician communication plans or elements to ~~all~~assure ofsafe ~~the~~use, ~~nonclinical~~such as restricted distribution methods, patient registries and ~~adequate~~other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling, development of adequate controls and ~~well~~specifications or a commitment to conduct one or more post-~~controlled~~market studies or clinical ~~trials~~studies. ~~necessary~~Such post-market testing may include Phase 4 clinical studies and surveillance to ~~demonstrate~~further assess and monitor the product’s safety and effectiveness after commercialization. The FDA may have the authority to withdraw its approval if post-market testing fails to verify the approved drug’s clinical benefit, if the applicant does not perform the required testing with due diligence, or if the any other evidence demonstrates the approved drug is not safe or effective, among other reasons. Also, new government requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval of our products under development.

Other types of exclusivities in the United States include orphan drug exclusivity and pediatric exclusivity. The FDA may grant orphan drug designation to a drug intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for this type of disease or condition will be recovered from sales in the United States for that drug. Seven-year orphan drug exclusivity is available to a product that has orphan drug designation and that receives the first FDA approval for the indication for which the drug has such designation. Orphan drug exclusivity prevents approval of another application for the same drug for the same orphan indication, for a period of seven years, regardless of whether the application is a full NDA or a Section 505(b)(2) NDA, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity. Pediatric exclusivity, if granted, provides an additional six months to an existing exclusivity or statutory delay in approval resulting from a patent certification. This six-month exclusivity, which runs from the end of other exclusivity protection or patent delay, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study. 50

61 Expedited Review and Accelerated Approval Programs

~~Section~~The FDA ~~505(b)(2)~~has ~~NDAs~~various programs, including fast track designation, breakthrough therapy designation, accelerated approval, regenerative medicine advanced therapy and priority review, that are ~~similar~~intended to ~~full~~expedite ~~NDAs~~the ~~filed~~development ~~under~~and ~~Section~~approval ~~505(b)(1)~~of innew drugs and biologics that ~~they~~address unmet ~~are~~medical ~~entitled~~needs toin ~~any~~the treatment of ~~these~~serious ~~forms~~or life-threatening diseases and conditions. To be eligible for a fast-track designation, the FDA must determine, based on the request of ~~exclusivity~~a ifsponsor, ~~they~~that ~~meet~~a product is intended to treat a serious or life-threatening disease or condition and demonstrates the ~~qualifying~~potential ~~criteria~~to address an unmet medical need. ~~They~~The ~~also~~FDA ~~are~~may ~~entitled~~review tosections of the ~~patent~~NDA ~~protections~~for ~~described~~a ~~above~~fast-track product on a rolling basis before the complete application is submitted, ~~based~~if onthe ~~patents~~sponsor ~~that~~provides ~~are~~a ~~listed~~schedule infor the submission of the sections of the NDA, the FDA’s ~~Orange~~agrees ~~Book~~to inaccept sections of the ~~same~~NDA ~~manner~~and asdetermines ~~patents~~that ~~claiming~~the ~~drugs~~schedule is acceptable, and ~~uses~~the ~~approved~~sponsor ~~for~~pays any ~~NDAs~~required ~~submitted~~user asfees ~~full~~upon ~~NDAs~~submission of the first section of the NDA.

~~Breakthrough~~The FDA ~~Therapy~~may ~~Designation~~give a priority review designation to drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists. A priority review means that the goal for the FDA to review an application is six months, rather than the standard review of ten months under current. These six and ten-month review periods are measured from the “filing” date rather than the receipt date for NDAs for new molecular entities, which typically adds approximately two months to the timeline for review and decision from the date of submission. Most products that are eligible for fast-track designation are also likely to be considered appropriate to receive a priority review.

~~The~~In addition, ~~Food~~products studied for their safety and ~~Drug~~effectiveness ~~Administration~~in treating serious or life-threatening illnesses and that provide meaningful ~~Safety~~therapeutic benefit over existing treatments may be eligible for accelerated approval and ~~Innovation~~may ~~Act~~be approved on the basis of adequate and well-controlled clinical studies establishing that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or ~~FDASIA~~on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, ~~Section~~that ~~902~~is ~~provides~~reasonably likely ~~for~~to ~~Breakthrough~~predict ~~Therapy~~an ~~designation~~effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments. AAs ~~Breakthrough~~a ~~Therapy~~condition isof approval, the FDA may require a sponsor of a drug: receiving accelerated approval to perform post-marketing studies to verify and describe the predicted effect on irreversible morbidity or mortality or other clinical endpoint, and the drug may be subject to accelerated withdrawal procedures.

●Moreover, under the provisions of the FDA Safety and Innovation Act passed in July 2012, a sponsor can request designation of a drug candidate as a “breakthrough therapy.” A breakthrough therapy is defined as a drug or biologic that is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition;, and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Drugs designated as breakthrough therapies are also eligible for the other expedited review and approval programs, including accelerated approval, priority review, regenerative medicine advanced therapy, and fast-track designation. The FDA must take certain actions, such as holding timely meetings and providing advice, intended to expedite the development and review of an application for approval of a breakthrough therapy.

●In addition, the 21st Century Cures Act in 2016 made the Regenerative Medicine Advanced Therapy, or RMAT, designation available for investigational drugs that are intended to treat, modify, reverse, or cure a serious condition, with preliminary clinical evidence ~~indicates~~indicating that the drug ~~may~~has ~~demonstrate~~the ~~substantial~~potential ~~improvement~~for ~~over~~addressing ~~existing~~unmet ~~therapies~~medical onneeds ~~one~~for such condition. The RMAT designation is available for cell therapy, therapeutic tissue engineering products, human cell and tissue products, and combination products that use such therapies or ~~more~~products. ~~clinically~~The ~~significant~~advantages of ~~endpoints~~RMAT designation include those of breakthrough and fast track designations, such as ~~substantial~~early ~~treatment~~interactions ~~effects~~with ~~observed~~FDA ~~early~~and inrolling review of applications, and the drug candidate with the RMAT designation may be eligible for accelerated approval. Requests for RMAT designations should be made with the IND application (if preliminary clinical ~~development~~evidence is available), but no later than the end-of-phase-2 meeting.

~~Fast~~Even if ~~Track~~a ~~Designation~~product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

~~A Fast Track is a designation~~Post-Approval ~~by the FDA of an investigational drug which:~~Requirements

●Drugs and ~~intended~~biologics ~~alone~~marketed orpursuant into ~~combination~~FDA ~~with~~approvals ~~one~~are orsubject ~~more~~to pervasive and continuing regulation by the FDA, including, among other things, ~~drugs~~requirements relating to ~~treat~~recordkeeping, aperiodic ~~serious~~reporting, orproduct ~~life-threatening~~sampling ~~disease~~and distribution, advertising and promotion and reporting of adverse experiences with the product. After approval, most changes to the approved product, such as adding new indications or ~~condition;~~other labeling claims are subject to prior FDA review and approval. There also are continuing, annual user fee requirements.

~~● non-clinical or clinical data demonstrate the potential to address an unmet medical need~~ 51

~~Fast~~Manufacturers ~~track~~are issubject ato ~~process~~periodic ~~designed~~unannounced toinspections ~~facilitate~~by the ~~development~~FDA and ~~expedite~~state ~~the~~agencies ~~review~~for ofcompliance ~~drugs~~with tocGMP ~~treat~~requirements. ~~serious~~Changes ~~conditions~~to ~~and~~the ~~fill~~manufacturing anprocess ~~unmet~~are ~~medical~~strictly ~~need.~~regulated ~~The~~and, ~~benefits~~depending ofon athe ~~Fast~~significance ~~Track~~of ~~designation~~the ~~include~~change, ~~rolling~~may ~~submission~~require ofprior ~~portions~~FDA ofapproval ~~the~~before ~~NDA~~being ~~for the drug~~implemented. ~~candidate~~FDA ~~and~~regulations ~~eligibility~~also ~~for~~require ~~priority~~investigation ~~review~~and correction of ~~the~~any ~~NDA.~~deviations ~~Additionally,~~from ~~more~~cGMP ~~frequent~~and ~~meetings~~impose reporting and ~~written~~documentation ~~communication~~requirements upon ~~with~~us ~~the FDA~~and ~~regarding~~any ~~the~~third-party ~~development~~manufacturers ~~plan~~that ~~and~~we ~~trial~~may ~~design~~decide ~~for~~to ~~the~~use. ~~drug~~Accordingly, ~~candidate~~manufacturers ~~are~~must ~~encouraged~~continue ~~throughout~~to ~~the~~expend ~~entire~~time, ~~drug~~money ~~development~~ and effort ~~review~~in ~~process, with~~ the ~~goal~~area of ~~having~~production ~~earlier~~and ~~drug~~quality ~~approval~~control to maintain compliance with cGMP and ~~access~~other ~~for~~aspects ~~patients~~of regulatory compliance.

Discovery of previously unknown problems with a product or the failure to comply with applicable requirements may result in restrictions on a product, manufacturer or holder of an approved NDA or BLA, including withdrawal or recall of the product from the market or other voluntary, FDA-initiated or judicial action that could delay or prohibit further marketing. Also, new government requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval of our products under development.

The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things.

●

restrictions on the marketing or manufacturing of the product;

●

complete withdrawal of the product from the market or product recalls;

●

fines, warning letters or holds on post-approval clinical studies;

●

refusal of the FDA to approve pending NDAs or BLAs or supplements to approved NDAs or BLAs, or suspension or revocation of product licenses or approvals;

●

product seizure or detention, or refusal to permit the import or export of products; or

●

injunctions or the imposition of civil or criminal penalties.

The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.

Pediatric Exclusivity

Pediatric exclusivity is another type of non-patent marketing exclusivity in the United States and, if granted, provides for the attachment of an additional six months to the term of any existing patent or regulatory exclusivity for drug products. This six-month exclusivity may be granted if an NDA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data. The data do not need to show the product to be effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted. If reports of requested pediatric studies are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity or patent protection cover the product are extended by six months. This is not a patent term extension, but effectively extends the regulatory period during which the FDA cannot approve another application. With regard to patents, the six-month pediatric exclusivity period will not attach to any patents for which a generic (ANDA or 505(b)(2) NDA) sponsor submitted a Paragraph IV certification, unless the NDA sponsor or patent owner first obtains a court determination that the patent is valid and infringed by a proposed generic product.

Orphan Designation and Exclusivity

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 individuals in the United States, or a patient population greater than 200,000 individuals in the United States and when there is no reasonable expectation that the cost of developing and making available the drug or biologic in the United States will be recovered from sales in the United States for that drug or biologic. Orphan drug designation must be requested before submitting a BLA or NDA. After the FDA grants orphan drug designation, the generic identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.

If a product that has orphan drug designation subsequently receives the first FDA approval for a particular active ingredient for the disease for which it has such designation, the product is entitled to orphan product marketing exclusivity, which means that the FDA may not approve any other applications, including a full BLA, to market the same biologic for the same use or indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or if FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was designated. Orphan drug exclusivity does not prevent the FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition. Among the other benefits of orphan drug designation are tax credits for certain research and a waiver of the BLA or NDA application user fee.

A designated orphan drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received orphan designation. In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or, as noted above, if the second applicant demonstrates that its product is clinically superior to the approved product with orphan exclusivity or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Biosimilars and Exclusivity

The Affordable Care Act, signed into law in 2010, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product. To date, only a handful of biosimilars have been licensed under the BPCIA, although numerous biosimilars have been approved in Europe. The FDA has issued several guidance documents outlining an approach to review and approval of biosimilars.

Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity and potency, can be shown through analytical studies, human PK and PD studies, clinical immunogenicity assessments, animal studies and a clinical study or studies. Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic. However, complexities associated with the larger, and often more complex, structures of biological products, as well as the processes by which such products are manufactured, pose significant hurdles to implementation of the abbreviated approval pathway that are still being worked out by the FDA.

Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first licensed by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference product was first licensed. During this 12-year period of exclusivity, another company may still market a competing version of the reference product if the FDA approves a full BLA for the competing product containing that applicant’s own preclinical data and data from adequate and well-controlled clinical studies to demonstrate the safety, purity and potency of its product. The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products. At this juncture, it is unclear whether products deemed “interchangeable” by the FDA will, in fact, be readily substituted by pharmacies, which are governed by state pharmacy law.

A biological product can also obtain pediatric market exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study.

The BPCIA is complex and continues to be interpreted and implemented by the FDA. In addition, recent government proposals have sought to reduce the 12-year reference product exclusivity period. Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation. As a result, the ultimate impact, implementation, and impact of the BPCIA is subject to significant uncertainty.

Hatch-Waxman Amendments, 505(b)(2) NDAs and Exclusivity

Section 505 of the FDCA describes three types of marketing applications that may be submitted to the FDA to request marketing authorization for a new drug. A Section 505(b)(1) NDA is an application that contains full reports of investigations of safety and efficacy. A 505(b)(2) NDA is an application that contains full reports of investigations of safety and efficacy but where at least some of the information required for approval comes from investigations that were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted. This regulatory pathway enables the applicant to rely, in part, on the FDA’s prior findings of safety and efficacy for an existing product, or published literature, in support of its application. Section 505(j) establishes an abbreviated approval process for a generic version of approved drug products through the submission of an ANDA. An ANDA provides for marketing of a generic drug product that has the same active ingredients, dosage form, strength, route of administration, labeling, performance characteristics and intended use, among other things, to a previously approved product. ANDAs are termed “abbreviated” because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and efficacy. Instead, generic applicants must scientifically demonstrate that their product is bioequivalent to, or performs in the same manner as, the innovator drug through in vitro, in vivo or other testing. The generic version must deliver the same amount of active ingredients into a subject’s bloodstream in the same amount of time as the innovator drug and can often be substituted by pharmacists under prescriptions written for the reference listed drug. In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent with claims that cover the applicant’s drug or a method of using the drug. Upon approval of a drug, each of the patents listed in the application for the drug is then published in the Orange Book. Drugs listed in the Orange Book can, in turn, be cited by potential competitors in support of approval of an ANDA or 505(b)(2) NDA.

Upon submission of an ANDA or a 505(b)(2) NDA, an applicant must certify to the FDA that (1) no patent information on the drug product that is the subject of the application has been submitted to the FDA; (2) such patent has expired; (3) the date on which such patent expires; or (4) such patent is invalid or will not be infringed upon by the manufacture, use or sale of the drug product for which the application is submitted. Generally, the ANDA or 505(b)(2) NDA cannot be approved until all listed patents have expired, except where the ANDA or 505(b)(2) NDA applicant challenges a listed patent through the last type of certification, also known as a paragraph IV certification. If the applicant does not challenge the listed patents or indicates that it is not seeking approval of a patented method of use, the ANDA or 505(b)(2) NDA application will not be approved until all of the listed patents claiming the referenced product have expired.

If the ANDA or 505(b)(2) NDA applicant has provided a Paragraph IV certification to the FDA, the applicant must send notice of the Paragraph IV certification to the NDA and patent holders once the application has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the paragraph IV certification. If the paragraph IV certification is challenged by an NDA holder or the patent owner(s) asserts a patent challenge to the paragraph IV certification, the FDA may not approve that application until the earlier of 30 months from the receipt of the notice of the paragraph IV certification, the expiration of the patent, when the infringement case concerning each such patent was favorably decided in the applicant’s favor or settled, or such shorter or longer period as may be ordered by a court. This prohibition is generally referred to as the 30-month stay. In instances where an ANDA or 505(b)(2) NDA applicant files a paragraph IV certification, the NDA holder or patent owner(s) regularly take action to trigger the 30-month stay, recognizing that the related patent litigation may take many months or years to resolve.

The FDA also cannot approve an ANDA or 505(b)(2) application until all applicable non-patent exclusivities listed in the Orange Book for the branded reference drug have expired. For example, a pharmaceutical manufacturer may obtain five years of non-patent exclusivity upon NDA approval of a new chemical entity, or NCE, which is a drug containing an active moiety that has not been approved by FDA in any other NDA. An “active moiety” is defined as the molecule responsible for the drug substance’s physiological or pharmacologic action. During that five-year exclusivity period, the FDA cannot accept for filing (and therefore cannot approve) any ANDA seeking approval of a generic version of that drug or any 505(b)(2) NDA that relies on the FDA’s approval of the drug, provided that that the FDA may accept an ANDA four years into the NCE exclusivity period if the ANDA applicant also files a Paragraph IV certification.

A drug, including one approved under Section 505(b)(2), may obtain a three-year period of exclusivity for a particular condition of approval, or change to a marketed product, such as a new formulation for a previously approved product, if one or more new clinical studies (other than bioavailability or bioequivalence studies) was essential to the approval of the application and was conducted/sponsored by the applicant. Should this occur, the FDA would be precluded from approving any ANDA or 505(b)(2) application for the protected modification until after that three-year exclusivity period has run. However, unlike NCE exclusivity, the FDA can accept an application and begin the review process during the exclusivity period.

A Section 505(b)(2) NDA may be submitted for a drug for which one or more of the investigations relied upon by the applicant was not conducted by or for the applicant and for which the applicant has no right of reference from the person by or for whom the investigations were conducted. A Section 505(b)(2) NDA may be submitted based in whole or in part on published literature or on the FDA’s finding of safety and efficacy of one or more previously approved drugs, which are known as reference drugs. Thus, the filing of a Section 505(b)(2) NDA may result in approval of a drug based on fewer clinical or nonclinical studies than would be required under a full NDA. The number and size of studies that need to be conducted by the sponsor depends on the amount and quality of data pertaining to the reference drug that are publicly available, and on the similarity of and differences between the applicant’s drug and the reference drug. In some cases, extensive, time-consuming, and costly clinical and nonclinical studies may still be required for approval of a Section 505(b)(2) NDA.

Our drug approval strategy for our new formulations of approved chemical entities is to submit Section 505(b)(2) NDAs to the FDA. TONMYA was approved as a Section 505(b)(2) NDA and we plan to submit an 505(b)(2)for TNX-2900 for Prader Willi Syndrome. The FDA may not agree that our product candidates are approvable as Section 505(b)(2) NDAs. If the FDA determines that a Section 505(b)(2) NDA is not appropriate and that a full NDA is required, the time and financial resources required to obtain FDA approval could substantially and materially increase and be less likely to be approved. If the FDA requires a full NDA or requires more extensive testing and development for some other reason, our ability to compete with alternative products that arrive on the market more quickly than our product candidates would be adversely impacted. If reference listed products are withdrawn from the market by the FDA for a safety reason, we may not be able to reference such products to support our anticipated 505(b)(2) NDAs, and we may be required to follow the requirements of Section 505(b)(1).

Patent Term Restoration and Extension

A patent claiming a new drug product, its method of use or its method of manufacture may be eligible for a limited patent term extension under the Hatch-Waxman Act, which permits a patent restoration of up to five years for patent term lost during product development and the FDA regulatory review. The restoration period granted on a patent covering a product is typically one-half the time between the effective date of when a clinical trial involving human beings has begun and the submission date of an application for approval, plus the time between the submission date of an application and the ultimate approval date. Patent term restoration cannot be used to extend the remaining patent term past a total of 14 years from the product’s approval date. Only one patent applicable to an approved product is eligible for the extension, and the application for the extension must be submitted prior to the expiration of the patent in question. A patent that covers multiple products for which approval is sought can only be extended in connection with one of the approvals. The USPTO reviews and approves the application for any patent term extension or restoration in consultation with the FDA.

Material Threat Medical Countermeasures

In 2016, the 21^stCentury Cures Act, or Act, was signed into law to support ongoing biomedical innovation. One part of the Act, Section 3086, is aimed at “Encouraging Treatments for Agents that Present a National Security Threat.” The Act created a new priority review voucher program for approved “material threat medical countermeasure applications.” The Act defines such countermeasures as drug or biological products, including vaccines intended to treat biological, chemical, radiological, or nuclear agents that present a national security threat or to treat harm from a condition that may be caused by administering a drug or biological product against such an agent. The Department of Homeland Security has identified 13 such threats, including anthrax, smallpox, Ebola/Marburg, tularemia, botulinum toxin, and pandemic influenza, which includes SARS-CoV-2.

62 Other Healthcare Laws and Compliance Requirements

~~Other~~Pharmaceutical companies ~~Regulatory~~are ~~Requirements~~subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business. Such laws include, without limitation, state and federal anti-kickback, fraud and abuse, false claims, privacy and security and physician sunshine laws and regulations. If their operations are found to be in violation of any of such laws or any other governmental regulations that apply, they may be subject to penalties, including, without limitation, civil and criminal penalties, damages, fines, the curtailment or restructuring of operations, exclusion from participation in federal and state healthcare programs and individual imprisonment.

Maintaining substantial compliance with appropriate federal, state and local statutes and regulations requires the expenditure of substantial time and financial resources. Drug manufacturers are required to register their establishments with the FDA and certain state agencies, and after approval, the FDA and these state agencies conduct periodic unannounced inspections to ensure continued compliance with ongoing regulatory requirements, including cGMPs. In addition, after approval, some types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further FDA review and approval. The FDA may require post-approval testing and surveillance programs to monitor safety and the effectiveness of approved products that have been commercialized. Any drug products manufactured or distributed by us pursuant to FDA approvals are subject to continuing regulation by the FDA, including:

● record-keeping requirements;

● reporting of adverse experiences with the drug;

● providing the FDA with updated safety and efficacy information;

● reporting on advertisements and promotional labeling;

● drug sampling and distribution requirements; and

● complying with electronic record and signature requirements.

In addition, the FDA strictly regulates labeling, advertising, promotion and other types of information on products that are placed on the market. There are numerous regulations and policies that govern various means for disseminating information to health-care professionals as well as consumers, including to industry sponsored scientific and educational activities, information provided to the media and information provided over the Internet. Drugs may be promoted only for the approved indications and in accordance with the provisions of the approved label.

The FDA has very broad enforcement authority and the failure to comply with applicable regulatory requirements can result in administrative or judicial sanctions being imposed on us or on the manufacturers and distributors of our approved products, including warning letters, refusals of government contracts, clinical holds, civil penalties, injunctions, restitution and disgorgement of profits, recall or seizure of products, total or partial suspension of production or distribution, withdrawal of approvals, refusal to approve pending applications, and criminal prosecution resulting in fines and incarceration. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability. In addition, even after regulatory approval is obtained, later discovery of previously unknown problems with a product may result in restrictions on the product or even complete withdrawal of the product from the market.

Coverage and Reimbursement

Sales of ~~our~~any product ~~candidates, if approved, will~~ depend, in part, on the extent to which such ~~products~~product will be covered by third-party payors, such as ~~government~~federal, ~~health~~state ~~care~~and foreign government healthcare programs, commercial insurance and managed healthcare organizations. ~~These~~and the level of reimbursement for such product by third-party payors ~~are~~. ~~increasingly~~Decisions ~~limiting~~regarding the extent of coverage orand amount of reimbursement to be provided are made on a plan-by-plan basis. These third-party payors are increasingly reducing reimbursements for medical products, drugs and services. In addition, the U.S. government, state legislatures and foreign governments have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products. ~~Third-party~~Adoption ~~payors~~of ~~decide~~price ~~which therapies they will pay~~controls ~~for~~ and ~~establish reimbursement levels. Third~~cost-~~party~~containment ~~payors~~measures, ~~often~~and ~~rely~~adoption ~~upon~~of ~~Medicare~~more ~~coverage~~restrictive ~~policy~~policies ~~and payment limitations~~ in ~~setting~~ ~~their~~jurisdictions ~~own~~with ~~coverage~~existing controls and ~~reimbursement policies. However~~measures, ~~decisions~~could further ~~regarding~~limit ~~the~~sales ~~extent~~ of ~~coverage~~any ~~and~~product. ~~amount~~Decreases ofin third-party reimbursement to ~~be provided~~ for any ~~drug~~product ~~candidates~~or ~~that~~a wedecision ~~develop~~by ~~will be made on~~ a ~~payor~~ third-~~by-payor basis.~~party ~~Each~~ payor ~~determines~~not to ~~whether~~cover ora ~~not~~product itcould ~~will~~reduce ~~provide~~physician ~~coverage~~usage ~~for~~and apatient ~~therapy,~~demand ~~what~~for ~~amount~~the itproduct ~~will~~and ~~pay~~also ~~the~~have ~~manufacturer~~a ~~for~~material ~~the~~adverse ~~therapy,~~effect ~~and~~ on ~~what~~sales. ~~tier~~Even ofafter ~~its~~FDA ~~formulary~~approves ita ~~will~~product, befailure ~~placed.~~to ~~The~~have ~~position~~the onproduct acovered ~~payor’s~~by ~~list~~third-party ofpayors ~~covered~~may ~~drugs,~~have ormaterial ~~formulary,~~adverse ~~generally~~effect ~~determines~~on ~~the co-payment that~~sales. Federal aand ~~patient~~state ~~will~~governments ~~need~~continue to ~~make~~promulgate tonew ~~obtain~~policies ~~the therapy~~ and ~~can~~regulations; ~~strongly~~such ~~influence~~policies ~~the~~and ~~adoption~~regulations ofmay ~~such~~have ~~therapy~~material byadverse ~~patients~~effect on ~~and physicians~~sales. ~~Adoption~~ ofThese ~~price~~laws ~~controls~~ and ~~cost-containment~~regulations ~~measures~~may restrict, ~~and~~prohibit, ~~adoption~~or ofpreventing ~~more~~us ~~restrictive~~from ~~policies~~implementing ina ~~jurisdictions~~wide ~~with~~range ~~existing controls~~of ~~and~~pricing, ~~measures~~discounting, marketing, ~~could~~promotion, ~~further~~sales ~~limit~~commission, ~~our~~incentive ~~net~~programs, ~~revenue~~ and ~~results~~other business activities. ~~Decreases~~No inuniform ~~third-party~~policy ~~reimbursement~~of ~~for~~coverage ~~our~~and ~~product~~reimbursement ~~candidates~~among ~~or a decision by a~~ third-party ~~payor~~payors toexists ~~not~~in ~~cover~~the ~~our~~United ~~product~~States. ~~candidates~~Such ~~could~~payors ~~reduce~~often ~~physician~~rely ~~usage~~upon ofMedicare ~~our~~coverage ~~product~~policy establishing their coverage ~~candidates,~~and ~~once~~reimbursement ~~approved~~policies. However, ~~and~~each ~~have~~payor amakes ~~material~~independent ~~adverse~~and ~~effect~~separate ondecisions ~~our~~regarding ~~sales,~~the ~~results~~extent of ~~operations~~coverage and ~~financial~~amount of ~~condition~~reimbursement to be provided.

~~Other Healthcare Laws~~ 55

~~Because~~Legislative ~~of our current~~ and ~~future~~Regulatory ~~arrangements with healthcare professionals~~Changes, ~~principal~~Including ~~investigators,~~Health ~~consultants,~~Care customers and third-party payors, we will also be subject to healthcare regulation and enforcement by the federal government and the states and foreign governments in which we will conduct our business, including our clinical research, proposed sales, marketing and educational programs. Failure to comply with these laws, where applicable, can result in the imposition of significant civil penalties, criminal penalties, or both. Reform

63The laws and regulation that affect our business are subject to change from time to time, and entirely new laws and regulations are sometimes adopted. In particular, healthcare reforms that have been adopted, and that may be adopted in the future, could result in further reductions in coverage and levels of reimbursement for pharmaceutical products, increases in rebates payable under U.S. government rebate programs and additional downward pressure on pharmaceutical product prices. Individual states in the United States have also become increasingly active in implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, proposing to encourage importation from other countries and bulk purchasing. It is unclear to what extent these and other statutory, regulatory, and administrative initiatives will be enacted and implemented.

~~The~~Foreign ~~U.S.~~Corrupt ~~laws~~Practices ~~that may affect our ability to operate, among others, include: the federal Health Insurance Portability and Accountability~~ Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information; certain state laws governing the privacy and security of health information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; the federal healthcare programs’ Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in exchange for or to induce either the referral of an individual for, or the purchase, order or recommendation of, any good or service for which payment may be made under federal healthcare programs such as the Medicare and Medicaid programs; federal false claims laws which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent; federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; the Physician Payments Sunshine Act, which requires manufacturers of drugs, devices, biologics, and medical supplies to report annually to the U.S. Department of Health and Human Services information related to payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, and ownership and investment interests held by physicians and their immediate family members; and state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers.

InOur business ~~addition~~activities may be subject to the Foreign Corrupt Practices Act, ~~many~~or ~~states have~~FCPA, and similar ~~laws~~anti-bribery ~~and~~or anti-corruption laws, regulations or rules of other countries in which we operate. The FCPA generally prohibits offering, ~~such~~promising, asgiving, ~~anti~~or authorizing others to give anything of value, either directly or indirectly, to a non-~~kickback~~U.S. government official in order to influence official action, or otherwise obtain or retain business. The FCPA also requires public companies to make and ~~false~~keep ~~claims~~books ~~laws~~and records that ~~may~~accurately beand ~~broader~~fairly inreflect the ~~scope~~transactions of the corporation and ~~may~~to ~~apply~~devise ~~regardless~~ and maintain an adequate system of ~~payor~~internal accounting controls. Our business is heavily regulated and therefore involves significant interaction with public officials, including officials of non-U.S. governments. Additionally, in ~~addition~~many toother ~~items~~countries, the health care providers who prescribe pharmaceuticals are employed by their government, and ~~services~~the ~~reimbursed~~purchasers of pharmaceuticals are government entities; therefore, our dealings with these prescribers and purchasers are subject to regulation under the ~~Medicaid~~FCPA. There is no certainty that all of our employees, agents, suppliers, manufacturers, contractors, or collaborators, or those of our affiliates, will comply with all applicable laws and ~~other~~regulations, ~~state~~particularly ~~programs~~given the high level of complexity of these laws. Violations ~~Additionally~~of these laws and regulations could result in fines, criminal sanctions against us, our officers, or our employees, the closing down of facilities, including those of our suppliers and manufacturers, requirements to obtain export licenses, cessation of business activities in sanctioned countries, implementation of compliance programs, and prohibitions on the ~~extent~~conduct ~~that~~of our business. Any such violations could include prohibitions on our ~~product~~ability isto ~~sold~~offer our products in aone ~~foreign~~or ~~country~~more countries as well as difficulties in manufacturing or continuing to develop our products, weand ~~may~~could bematerially ~~subject~~damage our reputation, our brand, our international expansion efforts, our ability to ~~similar~~attract ~~foreign~~and ~~laws~~retain employees, and our business, prospects, operating results, and financial condition.

~~The~~European Union ~~Impact~~Drug ~~of New Legislation and Amendments to Existing Laws~~Development

~~The FDCA is subject to routine legislative amendments with a broad range of downstream effects.~~ In ~~addition to new legislation, such as the FDA Reauthorization~~ ~~Act of 2017 or~~ the ~~FDASIA~~European ~~in 2012~~Union, Congress introduces amendments to reauthorize drug user fees and address emerging concerns every five years. We cannot predict the impact of these new legislative acts and their implementation of regulations on our ~~business. The~~product ~~programs~~candidates ~~established~~may oralso to be ~~established~~subject ~~under the legislation may have adverse effects upon us, including increased regulation of our industry. Compliance with such regulation may increase our costs and limit our ability~~ to ~~pursue~~extensive ~~business~~regulatory ~~opportunities~~requirements. In ~~addition,~~As in the ~~FDA’s~~United ~~regulations~~States, ~~policies~~medicinal products can ~~and~~only ~~guidance~~be ~~are~~marketed ~~often~~if ~~revised~~a ormarketing ~~reinterpreted~~authorization byfrom the ~~agency~~competent orregulatory ~~the~~agencies ~~courts in~~has ~~ways~~been ~~that may significantly affect our business and our products~~obtained.

WeSimilar ~~expect~~to ~~that~~the ~~additional~~United ~~federal~~States, the various phases of preclinical and ~~state,~~clinical asresearch ~~well~~in asthe ~~foreign,~~European ~~healthcare~~Union ~~reform~~are ~~measures~~subject ~~will~~to besignificant ~~adopted~~regulatory controls. Clinical trials of medicinal products in the ~~future,~~European ~~any~~Union ~~of which~~must ~~could~~be ~~result~~conducted in ~~reduced~~accordance ~~demand~~with ~~for~~European ~~our~~Union, ~~products~~national orregulations and ~~additional~~international ~~pricing~~standards ~~pressure~~for good clinical practice, or GCP.

Clinical trials are currently governed by EU Clinical Trials Directive 2001/20/EC that set out common rules for the control and authorization of clinical trials in the European Union.

To improve the current system, Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use was adopted in 2014. The Regulation aims at harmonizing and streamlining the clinical trials authorization process, simplifying adverse event reporting procedures, improving the supervision of clinical trials, and increasing their transparency, notably via a clinical trial information system set up by the EMA. The new Regulation expressly provides that it will not be applied before six months after the publication of a notice delivered by the European Commission on the European Union clinical trial portal and database. As such notice requires a successful (partial) audit of the database and as that database is still under development, there is no scheduled application date yet. Pursuant to the transitory provisions of the new regulation, the Clinical Trials Directive 2001/20/EC will still apply for three years after the implementation of the European Union clinical trial portal and database. Thus, the sponsor has the possibility to choose between the requirements of the directive and the regulation for a period of three years from the entry into force of the regulation.

European Union Drug Review and Approval

In the EEA (which is comprised of the 28 Member States of the European Union plus Norway, Iceland and Liechtenstein), medicinal products can only be commercialized after obtaining a Marketing Authorization, or MA. MAs may be granted either centrally (Community MA) or nationally (National MA).

The Community MA is issued centrally by the European Commission through the Centralized Procedure, based on the opinion of the CHMP of the EMA and is valid throughout the entire territory of the EEA. The Centralized Procedure is mandatory for certain types of products such as orphan medicinal products and medicinal products containing a new active substance indicated for the treatment of neurodegenerative disorders. The Centralized Procedure is optional for products containing a new active substance not yet authorized in the EEA, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the European Union.

National MAs are issued nationally by the competent authorities of the Member States of the EEA and only cover their respective territory. National MAs are available for products not falling within the mandatory scope of the Centralized Procedure. We do not foresee that any of our current product candidates will be suitable for a National MA as they fall within the mandatory criteria for the Centralized Procedure. Therefore, our product candidates will be approved through Community MAs.

Under the above-described procedures, before granting the MA, the EMA or the competent authorities of the Member States of the EEA make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.

The pediatric use marketing authorization, or PUMA, is a dedicated marketing authorization for medicinal products indicated exclusively for use in the pediatric population, with, if necessary, an age-appropriate formulation. Pursuant to Regulation (EC) No. 1901/2006 (The “Pediatric Regulation”), all PUMA applications for marketing authorization for new medicines must include to be valid, in addition to the particulars and documents referred to in Directive 2001/83/EC, the results of all studies performed and details of all information collected in compliance with a pediatric investigation plan agreed between regulatory authorities and the applicant, unless the medicine is exempt because of a deferral or waiver of the EMA.

Before the EMA is able to begin its assessment of a Community MA application, it will validate that the applicant has complied with the agreed pediatric investigation plan. The applicant and the EMA may, where such a step is adequately justified, agree to modify a pediatric investigation plan to assist validation. Modifications are not always possible; may take longer to agree than the period of validation permits; and may still require the applicant to withdraw its marketing authorization application and to conduct additional non-clinical and clinical studies. Products that are granted a MA on the basis of the pediatric clinical trials conducted in accordance with the Pediatric Investigation Plan, or PIP, are eligible for a six-month extension of the protection under a supplementary protection certificate (if any is in effect at the time of approval) or, in the case of orphan medicinal products, a two-year extension of the orphan market exclusivity. This pediatric reward is subject to specific conditions and is not automatically available when data in compliance with the PIP are developed and submitted.

Orphan Drugs

In the European Union, Regulation (EC) No 141/2000 of the European Parliament and of the Council of December 16, 1999 on orphan medicinal products, as amended, states that a drug shall be designated as an orphan drug if its sponsor can establish that the three following cumulative conditions are met:

●

the product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition;

●

the prevalence of the conditions is not more than five in ten thousand persons in the European Union when the application is made, or that it is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the European Union and that without incentives it is unlikely that the marketing of the drug in the European Union would generate sufficient return to justify the necessary investment; and

●

that there is no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized in the European Union or, if such method exists, that the drug will be of significant benefit to those affected by that condition.

Pursuant to Regulation (EC) No. 847/2000 of April 27, 2000 laying down the provisions for implementation of the criteria for designation of a medicinal product as an orphan medicinal product and definitions of the concepts “similar medicinal product” and “clinical superiority”, an application for the designation of a drug as an orphan drug must be submitted at any stage of development of the drug before filing of a MA application.

The European Union offers incentives to encourage the development of designated orphan medicines (protocol assistance, fee reductions, etc.) and provides opportunities for market exclusivity. Pursuant to abovementioned Regulation (EC) No. 141/2000, products receiving orphan designation in the European Union can obtain market exclusivity for a certain number of years in the European Union following the marketing approval.

If a Community MA in respect of an orphan drug is granted, regulatory authorities will not, for a period of usually ten years, accept another application for a MA, or grant a MA or accept an application to extend an existing MA, for the same therapeutic indication, in respect of a similar drug. This period may however be reduced to six years if, at the end of the fifth year, it is established, in respect of the drug concerned, that the above-mentioned criteria for orphan drug designation are no longer met, in other words, when it is shown on the basis of available evidence that the product is sufficiently profitable not to justify maintenance of market exclusivity.

Pursuant to Regulation No. 1901/2006, for orphan medicinal products, instead of an extension of the supplementary protection certificate, the ten-year period of orphan market exclusivity should be extended to 12 years if the requirement for data on use in the pediatric population is fully met (i.e. when the request contains the results of all studies carried out under the approved PIP and when the declaration attesting the conformity of the request to this PIP is included in the MA).

Notwithstanding the foregoing, a MA may be granted, for the same therapeutic indication, to a similar drug if:

●

the holder of the MA for the original orphan drug has given its consent to the second applicant;

●

the holder of the MA for the original orphan drug is unable to supply sufficient quantities of the drug; or

●

the second applicant can establish in the application that the second drug, although similar to the orphan drug already authorized, is safer, more effective or otherwise clinically superior.

The abovementioned Regulation (EC) No. 141/2000 provides for other incentives regarding orphan medicinal products.

Post-Approval Controls

The holder of a MA must comply with EU requirements applicable to manufacturing, marketing, promotion and sale of medicinal products. In particular, the holder of the MA must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance, or QPPV, who is responsible for oversight of that system and who will reside and operate in the EU. Key obligations include safety expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports, or PSURs.

All new MAs must include a risk management plan, or RMP, to submit to the EMA, describing the risk management system that the company will put in place and documenting measures to prevent or minimize the risks associated with the product. The regulatory authorities may also impose specific obligations as a condition of the MA. Such risk-minimization measures or post-authorization obligations may include additional safety monitoring, more frequent submission of PSURs, or the conduct of additional clinical trials or post-authorization safety studies. RMPs and PSURs are routinely available to third parties requesting access, subject to limited redactions. All advertising and promotional activities for the product must be consistent with the approved summary of product characteristics, and therefore all off-label promotion is prohibited. Direct-to-consumer advertising of prescription medicines is also prohibited in the European Union. Although general requirements for advertising and promotion of medicinal products are established under EU directives, the details are governed by regulations in each EU Member State and can differ from one country to another.

Reimbursement

The European Union provides options for its Member States to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. A Member State may approve a specific price for the medicinal product, or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market. For example, in France, effective market access will be supported by agreements with hospitals and products may be reimbursed by the Social Security Fund. The price of medicines covered by national health insurance is negotiated with the Economic Committee for Health Products, or CEPS. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our product candidates. Historically, products launched in the European Union do not follow price structures of the United States and generally prices tend to be significantly lower.

Human Capital Resources

As of March 1712, ~~2025~~2026, we had 81142 full-time employees, of whom 1229 hold M.D. or Ph.D. degrees. We have 4570 employees dedicated to research and development. We have ~~two~~10 employees supporting sales administration and marketing initiatives; ~~and three sales employees who are focused on~~ customer service requests and top-tier headache specialists. None of our employees are represented by a collective bargaining agreement. We believe that the skills, experience and industry knowledge of our key employees significantly benefit our operations and performance. Our research and development operations are located in ~~Chatham~~Berkeley Heights, New Jersey, Dartmouth, Massachusetts, Frederick, Maryland, Dublin, Ireland and Montreal, Canada. We have used, and expect to continue to use, third parties to conduct our nonclinical and clinical studies as well as part-time employees.

Employee health and safety in the workplace is one of our core values.

Employee levels are managed to align with the pace of business and management believes it has sufficient human capital to operate its business successfully.

Corporate Information

We lease the space for our principal executive offices, which are located at 26200 ~~Main~~Connell ~~Street~~Drive, Suite ~~101~~3100, ~~Chatham~~Berkeley Heights, New Jersey ~~07928~~07922, and our telephone number is (862) 799 8599. Our website address is www.tonixpharma.com. We do not incorporate the information on our websites into this ~~annual~~Annual ~~report~~Report, and you should not consider such information part of this ~~annual~~Annual ~~report~~Report.

We were incorporated on November 16, 2007, under the laws of the State of Nevada as Tamandare Explorations Inc. On October 11, 2011, we changed our name to Tonix Pharmaceuticals Holding Corp.

ITEM 1A – Risk Factors

Summary of Risk Factors

● ~~Our prospects are dependent on the continued successful commercialization of Tosymra and Zembrace, and on the success of TNX 102-SL. ●~~ We ~~are exposed to cybersecurity and data privacy risks that, if realized, could harm our business. ● We~~ have a history of operating losses and ~~may~~expect ~~never reach profitability. We may struggle~~ to ~~continue~~incur ~~operations~~losses ~~without~~for ~~facing~~ the ~~risk~~foreseeable offuture. ~~liquidation,~~We asmay wenever ~~don’t~~achieve ~~expect product sales to cover expenses~~profitability.

● IfWe ~~novel~~expect ~~product~~a ~~candidates~~number ~~are~~of ~~successfully~~factors ~~developed,~~to itcause isour ~~uncertain~~operating ~~they~~results ~~will~~to ~~receive~~fluctuate ~~regulatory~~on ~~approval~~a orquarterly ~~successful~~and ~~commercialization~~annual basis, which may make it difficult to predict our future performance.

● WeOur ~~are~~independent ~~subject~~registered topublic ~~extensive~~accounting ~~and~~firm ~~costly~~has ~~government~~included ~~regulation,~~an ~~and~~explanatory weparagraph dorelating ~~not~~to ~~have,~~our ~~and~~ability ~~may~~to ~~never~~continue ~~obtain,~~as ~~the~~a ~~regulatory~~going ~~approvals~~concern wein ~~need~~its toreport ~~market~~on our ~~product~~audited ~~candidates~~financial statements.

● ~~Our~~We ~~product~~will ~~candidates~~need ~~may~~additional ~~cause~~capital ~~serious adverse events or undesirable side effects, which would delay or prevent approval, or lead~~ to ~~market~~fund ~~removal,~~our ~~safety warnings, or sales limitations~~operations.

● WeOur ~~may~~prospects beare ~~unable~~highly todependent ~~meet~~on ~~our~~the ~~anticipated~~success ~~development~~of ~~and~~TONMYA. ~~commercialization~~If ~~timelines~~we ~~for~~are ~~approval~~unable ofto ~~any~~successfully ofcommercialize or maintain approval for TONMYA, our ~~product~~business ~~candidates~~will be materially adversely affected.

● ~~Changes~~We inhave ~~the~~a ~~U.S.~~limited ~~political~~operating history and ~~regulatory~~only ~~environment~~recently ~~could~~launched ~~affect~~TONMYA ~~availability~~in ofthe ~~government~~United ~~funding~~States, ~~that~~which we may ~~rely~~make ~~on,~~it ordifficult ~~cause~~to ~~delays~~evaluate in the ~~development~~prospects ~~and~~for ~~approval of~~ our ~~product~~future ~~candidates~~viability.

● ~~Any~~TONMYA ~~grant~~and ofour ~~priority~~migraine ~~review~~products ~~status~~remain bysubject ~~the~~to ~~FDA~~ongoing ~~may~~regulatory ~~not~~review, ~~actually~~and ~~lead~~if we fail to acomply ~~faster~~with ~~development~~continuing orregulations, ~~regulatory~~we ~~review~~could orlose our approval ~~process,~~and ~~nor~~the ~~assure~~sale ~~FDA~~of ~~approval~~TONMYA ofor our ~~product~~migraine ~~candidates~~products could be suspended.

● ~~Even~~If ifestimates ~~approved~~of the size of the potential market for TONMYA are overstated or data we have used to identify prescribing healthcare providers is inaccurate, our ~~products~~ability ~~may~~to beearn ~~subject~~revenue to ~~post-approval~~support ~~regulation~~our orbusiness ~~may~~could ~~not~~ be ~~accepted~~materially byadversely ~~the market~~affected.

● WeCoverage ~~may use our financial~~ and ~~human~~adequate ~~resources~~reimbursement tomay ~~pursue~~not ~~research~~be ~~programs~~available orfor ~~product~~our ~~candidates that are less profitable and have a lower likelihood of success than other programs~~products.

● WeHealthcare ~~may~~legislative ~~need~~or ~~additional~~regulatory ~~capital,~~reform ~~and~~measures, ifincluding ~~unavailable,~~government werestrictions on pricing and reimbursement, may have toa ~~delay~~negative orimpact ~~scale-back~~on our business and results of operations.

● ~~Outbreaks~~Even ofif ~~communicable~~we ~~diseases~~obtain ~~may~~regulatory ~~materially~~approval ~~and~~to ~~adversely~~market ~~affect~~our product candidates, our ~~business~~product candidates may not be accepted by the market.

● ~~Competition~~Uncertainty ~~and~~in ~~technological~~Government ~~change~~funding ~~may make our product candidates~~ and ~~technologies~~in-kind ~~less~~support ~~attractive~~policies ~~or obsolete,~~ and ~~our~~programs ~~product candidates~~ may ~~face~~adversely ~~competition~~affect ~~sooner~~our ~~than expected~~business.

● ~~Failure~~Our toproduct ~~protect~~candidates ~~our~~are ~~intellectual~~novel ~~property~~and ~~rights~~still ~~could~~in ~~negatively affect our~~ development ~~of products~~.

65 ● If preclinical and nonclinical testing or clinical studies for our product candidates are unsuccessful or delayed, we will be unable to meet our anticipated development and commercialization timelines.

● We ~~may~~are besubject ~~involved in lawsuits~~ to ~~protect~~extensive orand ~~enforce~~costly ~~our~~government ~~patents, which could be costly~~regulation.

● IfOur weproduct ~~infringe~~candidates ~~the~~may ~~rights~~cause ofserious ~~third~~adverse ~~parties~~events, weor ~~could suffer adverse effects~~SAEs, ~~including~~or ~~defending~~undesirable ~~against~~side ~~litigation~~effects.

● WeAny ~~may~~breakthrough, ~~experience~~fast ~~difficulties~~track ~~managing~~or ~~growth~~orphan ~~when~~drug wedesignation ~~ultimately~~or ~~expand~~grant ~~our~~of ~~operations.~~priority ~~Our~~review ~~future~~status ~~success~~by ~~depends~~the onFDA ~~our~~may ~~ability~~not toactually ~~retain~~lead ~~our~~to ~~current~~the ~~executive~~benefits ~~officers~~we ~~and other key personnel~~anticipate.

● ~~The~~Even ~~failure~~if ofapproved, ~~third parties to manufacture compounds used~~ our ~~studies,~~product ~~and~~candidates ~~any~~will ~~approved~~be ~~products~~subject ~~for~~to ~~sale~~extensive atpost-approval ~~sufficient quantities and at acceptable costs could harm our business~~regulation.

● ~~Failure~~Our byrelationships ~~our third-party manufacturers to comply~~ with ~~regulatory guidelines set forth by the FDA could harm the development~~customers, ~~approval~~physicians and ~~commercialization~~third-party ofpayors ~~our~~is ~~product~~subject ~~candidates.~~to ●federal ~~Adverse~~and ~~global~~state ~~conditions,~~healthcare ~~including~~laws ~~economic~~and uncertainty, may negatively impact our finances. ● Our internal computer systems may fail or suffer security breaches, which could result in a material disruption of our product development programs.regulations

● ~~Corporate~~If ~~and~~we ~~academic~~obtain ~~collaborators~~approval ~~may~~to ~~take~~commercialize ~~actions~~any toapproved ~~undermine~~products outside of the ~~success~~United States, a variety of risks associated with international operations could materially adversely affect our ~~products~~business.

●

Governments outside the United States tend to impose strict price controls, which may adversely affect our revenues, if any.

●

If the FDA approves generic products that compete with TONMYA, sales of TONMYA would be adversely affected.

●

The biopharmaceutical industry is subject to extensive regulatory obligations and policies that may be subject to change, including due to judicial challenges.

●

Reductions in staffing and funding at FDA and other federal agencies could cause delays in the development and approval of our products.

●

We may never receive regulatory approval to market our current or future product candidates outside of the U.S.

●

Our future growth may depend, in part, on our ability to penetrate foreign markets, where we would be subject to additional regulatory burdens and other risks and uncertainties that could materially adversely affect our business.

●

There may not be market interest in TNX-801.

●

If technology developed for the purposes of developing new medicines or vaccines can be applied to the creation or development of biological weapons, then our technology may be considered “dual use” technology and be subject to limitations on public disclosure or export.

●

Competition and technological change may make our product candidates and technologies less attractive or obsolete.

●

Failure to protect our intellectual property could materially adversely affect our business.

●

We are dependent on license relationships with third parties for certain of our drug development programs.

●

We may be involved in lawsuits to protect or enforce our patents, which could be expensive and time consuming.

●

If we infringe the rights of third parties we could be prevented from selling products, forced to pay damages, and defend against litigation.

●

There are risks to our intellectual property based on our international business initiatives.

●

We may be unable to protect the confidentiality of our trade secrets, thus harming our business and competitive position.

●

Third parties may assert that our employees or consultants have wrongfully used or disclosed confidential information or misappropriated trade secrets.

●

We may need to license intellectual property from third parties, and such licenses may not be available or may not be available on commercially reasonable terms.

●

We rely on third parties to conduct, supervise and monitor our clinical studies, and if those third parties perform in an unsatisfactory manner, it may harm our business.

●

We may use our financial and human resources to pursue a particular research program or product candidate and fail to capitalize on programs or product candidates that may be more profitable or for which there is a greater likelihood of success.

●

We will need to expand our operations and increase the size of our company, and we may experience difficulties in managing growth.

●

Our executive officers and other key personnel are critical to our business, and our future success depends on our ability to retain them.

●

If we are unable to hire additional qualified personnel, our ability to grow our business may be harmed.

●

We rely on, and expect to continue to rely on, third parties to manufacture our marketed products and the compounds used in our studies.

●

Failure by our third-party manufacturers to comply with the regulatory guidelines could delay or prevent the completion of clinical studies, the approval of any product candidates or the commercialization of our products.

●

We are exposed to cybersecurity and data privacy risks.

●

Adverse global conditions, including economic uncertainty, may negatively impact our financial results.

●

Our internal computer systems, or those of our CROs or other contractors or consultants, may fail or suffer security breaches.

●

Corporate and academic collaborators may take actions to delay, prevent, or undermine the success of our products.

●

Data provided by collaborators and others upon which we rely that has not been independently verified could turn out to be false, misleading, or incomplete.

● IfOur weproduct ~~fail~~candidates tomay ~~establish~~face ~~marketing,~~competition ~~sales~~sooner ~~and~~than ~~distribution capabilities, we will not be able to create a market for our product candidates~~expected.

● ~~Our~~We ~~relationships~~may ~~with customers, physicians, and third-party payors will~~ be ~~subject~~unable to ~~federal~~establish, ~~and~~or ~~state~~engage ~~healthcare~~third-parties ~~laws and regulations. If we are unable~~ to ~~comply with such laws~~provide, ~~including~~effective ~~any newly adopted healthcare legislative reform measures~~marketing, wesales ~~could~~and ~~face~~distribution ~~substantial penalties~~capabilities.

● Coverage and adequate reimbursement may not be available for our current or any future drug candidates, which could make it difficult for us to sell profitably, if approved.

● Obtaining approval to commercialize products outside the U.S. would expose us to international risk.

●

We face the risk of product liability claims and may not be able to obtain insurance.

● WePotential ~~use~~claims relating to improper handling, storage or disposal of hazardous chemicals used in our business ~~which~~ could ~~expose~~affect us ~~to costly~~ and ~~time~~be time-consuming ~~legal~~and ~~claims~~costly.

●

Our insurance policies are expensive and protect us only from some business risks, which will leave us exposed to significant uninsured liabilities.

●

If we retain collaborative partners and our partners do not satisfy their obligations, we will be unable to develop our partnered product candidates.

● We may be unsuccessful in obtaining a priority review voucher for material threat medical countermeasures.

● Government entities may take actions that directly or indirectly have the effect of limiting opportunities for our vaccines for COVID-19.

● If our technology is ever considered “dual use” technology, it will be subject to limitations on public disclosure or export.

●

We face risks in connection with existing and future collaborations with respect to the development, manufacture, and commercialization of our product candidates.

●

We face risks in connection with the testing, production and storage of our vaccine product candidates.

● ~~Sales~~Changes ofin ~~additional~~tax ~~shares~~laws ~~of our common stock~~ could ~~cause~~adversely ~~the~~affect ~~price of~~ our ~~common~~business ~~stock to decline,~~ and ~~the~~financial ~~issuance of preferred stock may impair the rights of the holders of common stock~~condition.

● ~~The~~Sales ~~market~~of ~~price~~additional shares of our common stock ~~has~~could ~~been~~cause ~~extremely~~the ~~volatile~~price ~~and may continue to be. We expect that our quarterly results~~ of ~~operations will fluctuate, which could cause~~ our common stock ~~price~~ to decline.

66 ● We may not be able to maintain compliance with the Listing Rules of the NASDAQ Stock Exchange.

● WeAn ~~could~~active betrading ~~delisted~~market ~~from~~for ~~Nasdaq, which could harm the liquidity of~~ our ~~stock~~common ~~and our capital raising. ● If we fail to comply with the rules under the Sarbanes-Oxley Act of 2002 related to accounting controls and procedures, our~~ stock ~~price~~may ~~could~~not ~~decline significantly and raising capital could~~ be ~~more difficult~~sustained. ● Other companies may have difficulty acquiring us, even if doing so would benefit our stockholders, due to provisions under our corporate charter and bylaws, as well as Nevada law. ● The Eighth Judicial District Court of Clark County, Nevada as the sole and exclusive forum for certain types of stockholder actions or proceedings, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us.

●

The market price of our common stock has been extremely volatile in the past and may be volatile in the future due to numerous circumstances beyond our control.

●

A “short squeeze” due to a sudden increase in demand for shares of our common stock that largely could lead to extreme price volatility in shares of our common stock.

●

We do not anticipate paying dividends on our common stock.

●

The rights of the holders of common stock may be impaired by the potential issuance of preferred stock.

●

If we fail to comply with the rules under the Sarbanes-Oxley Act of 2002 related to accounting controls and procedures, or if we discover material weaknesses and deficiencies in our internal control and accounting procedures, our stock price could decline significantly and raising capital could be more difficult.

●

If securities or industry analysts do not publish research or reports about our business, or if they change their recommendations regarding our stock adversely, our stock price and trading volume could decline.

●

Other companies may have difficulty acquiring us, even if doing so would benefit our stockholders, due to provisions under our corporate charter and bylaws, as well as Nevada law.

●

Our bylaws designate the Eighth Judicial District Court of Clark County, Nevada as the sole and exclusive forum for certain types of actions and proceedings that may be initiated by our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers, employees or agents.

RISKS RELATED TO OUR FINANCIAL CONDITION AND CAPITAL REQUIREMENTS

We have a history of operating losses and expect to incur losses for the foreseeable future. We may never achieve profitability.

We started generating revenues from product sales in the third quarter of 2023, and from sales of TONMYA in the fourth quarter of 2025. We have incurred losses in each year of our operations, and we expect to continue to incur operating losses for the foreseeable future as our sales and marketing, research, development, preclinical and nonclinical testing, and clinical study activities increase, and if and when we acquire rights to additional products and product candidates. The amount of future losses and when, if ever, we will achieve profitability are uncertain. Failure to achieve profitability could diminish our ability to sustain operations, pay dividends on our common stock, obtain additional required funds and make required payments on any future indebtedness. We have three products that have generated commercial revenue in the past two years, but we do not expect revenues from the commercial sale of products to exceed expenses in the near future. Our ability to generate revenue and achieve profitability will depend on, among other things, successfully commercializing our products; establishing a favorable competitive position; successful completion of the development of our product candidates; obtaining necessary regulatory approvals from the FDA; establishing manufacturing, sales, and marketing arrangements with third parties; and raising sufficient funds to finance our activities. Many of these factors will depend on circumstances beyond our control. We might not succeed at any of these undertakings. If we are unsuccessful at some or all of these undertakings, our business, prospects, and results of operations may be materially adversely affected.

We expect a number of factors to cause our operating results to fluctuate on a quarterly and annual basis, which may make it difficult to predict our future performance.

Our financial condition has varied significantly in the past and will continue to fluctuate from quarter-to-quarter and year-to-year due to a variety of factors, many of which are beyond our control. Factors relating to our business that may contribute to these fluctuations include other factors described elsewhere in this Annual Report and include, among other things:

●

our ability to obtain additional funding to commercialize our products and develop our product candidates;

●

market acceptance of our products;

●

the ability of patients or healthcare providers to obtain coverage of or sufficient reimbursement for our products;

●

our ability to maintain regulatory approval for TONMYA and our migraine products, and to obtain regulatory approval for our product candidates in the United States and foreign jurisdictions;

●

delays in the commencement, enrollment and timing of clinical studies;

●

the success of our clinical studies through all phases of clinical development;

●

any delays in regulatory review and approval of product candidates in clinical development;

●

potential nonclinical toxicity and/or side effects of our products or product candidates that could delay or prevent commercialization, limit the indications for any approved drug, require the establishment of a REMS, or cause an approved drug to be taken off the market;

●

our ability to establish or maintain collaborations, licensing or other arrangements;

●

competition from existing or new products;

●

our ability to leverage our proprietary technology platform to discover and develop additional product candidates;

●

our ability and our licensors’ abilities to successfully obtain, maintain, defend and enforce intellectual property rights important to our business; and

●

potential product liability claims.

Accordingly, the results of any quarterly or annual periods should not be relied upon as indications of future operating performance.

Our independent registered public accounting firm has included an explanatory paragraph relating to our ability to continue as a going concern in its report on our audited financial statements.

If we are unable to obtain sufficient funding, our business, prospects, financial condition and results of operations will be materially and adversely affected, and we may be unable to continue as a going concern. For example, we anticipate that our existing cash and cash equivalents will enable us to maintain our current operations into the first quarter of 2027. If we are unable to continue as a going concern, we may have to liquidate our assets and may receive less than the value at which those assets are carried on our consolidated financial statements, and investors will likely lose all or a part of their investment. Future reports from our independent registered public accounting firm may continue to include statements expressing substantial doubt about our ability to continue as a going concern. If we seek additional financing to fund our business activities in the future and there remains substantial doubt about our ability to continue as a going concern, investors or other financing sources may be unwilling to provide additional funding on commercially reasonable terms or at all. In connection with our management’s assessment, our report from our independent registered public accounting firm for the fiscal year ended December 31, 2025, includes an explanatory paragraph stating that our recurring losses from operations and net capital deficiency raise substantial doubt about our ability to continue as a going concern.

We will need additional capital to fund our operations. If additional capital is not available or is available at unattractive terms, we may be forced to delay, reduce the scope of or eliminate our research and development programs, reduce our commercialization efforts or curtail our operations.

In order to successfully commercialize our marketed products and develop and bring our product candidates to market, we must commit substantial resources to costly and time-consuming commercialization activities, research, preclinical and nonclinical testing, clinical studies and the buildout of our sales, research and development and manufacturing facilities. We anticipate that our existing cash and cash equivalents will enable us to maintain our current operations until the first quarter of 2027. We anticipate using our cash and cash equivalents to commercialize TONMYA and to fund further research and development with respect to our product candidates. We will, however, need to raise additional funding sooner if our business or operations change in a manner that consumes available resources more rapidly than we anticipate. Our requirements for additional capital will depend on many factors, including:

●

successful commercialization of our marketed products;

●

development of marketing and sales capabilities;

●

market acceptance of our products;

●

the time and costs involved in obtaining regulatory approval for our product candidates;

●

costs associated with protecting our intellectual property rights; and

●

payments received under future collaborative agreements, if any.

To the extent we raise additional capital through the sale of equity securities, the issuance of those securities could result in dilution to our shareholders. In addition, if we obtain debt financing, a substantial portion of our operating cash flow may be dedicated to the payment of principal and interest on such indebtedness, thus limiting funds available for our business activities. If adequate funds are not available, we may be required to delay, reduce the scope of or eliminate our research and development programs, reduce our commercialization efforts or curtail our operations. In addition, we may be required to obtain funds through arrangements with collaborative partners or others that may require us to relinquish rights to technologies, product candidates or products that we would otherwise seek to develop or commercialize ourselves or license rights to technologies, product candidates or products on terms that are less favorable to us than might otherwise be available.

We will require substantial funds to support our commercialization, research and development activities, and the anticipated costs of preclinical and nonclinical testing and clinical studies, regulatory approvals and eventual commercialization of our product candidates. Such additional sources of financing may not be available on favorable terms, if at all. If we do not succeed in raising additional funds on acceptable terms, we may be unable to commence or complete clinical studies or obtain approval of any product candidates from the FDA and other regulatory authorities. In addition, we could be forced to discontinue product development, forego sales and marketing efforts and forego attractive business opportunities. Any additional sources of financing will likely involve the issuance of our equity securities, which will have a dilutive effect on our shareholders.

There is no assurance that we will be successful in raising the additional funds needed to fund our business plan. If we are not able to raise sufficient capital in the near future, our continued operations will be in jeopardy, and we may be forced to cease operations and sell or otherwise transfer all or substantially all of our remaining assets.

RISKS RELATED TO OUR BUSINESS

Our prospects are highly dependent on the success of ~~TNX-102 SL~~TONMYA. ToIf ~~the~~we ~~extent~~are ~~regulatory~~unable ~~approval~~to ofsuccessfully ~~TNX-102~~commercialize ~~SL is delayed~~ or ~~not~~maintain ~~granted~~approval ~~or, if approved, TNX-102 SL is~~for ~~not commercially successful~~TONMYA, our business, financial condition, ~~and~~ results of operations ~~may~~and beprospects ~~materially adversely affected~~ and the ~~price~~value of our common stock ~~may~~will ~~decline~~be materially adversely affected.

~~The research, testing,~~In ~~manufacturing,~~August ~~labeling~~2025, ~~approval,~~the ~~sale,~~FDA ~~import,~~granted ~~export,~~approval ~~marketing, and distribution~~ of ~~pharmaceutical~~TONMYA ~~product~~for ~~candidates~~the ~~are~~treatment ~~subject to~~of ~~extensive regulation by the FDA~~fibromyalgia. We have ~~focused a significant portion of our activities and resources on the development of TNX-102 SL~~invested, and wecontinue ~~believe our prospects are also dependent on our ability~~ to ~~obtain~~invest, ~~regulatory~~significant efforts ~~approval for~~ and ~~successfully~~financial ~~commercialize TNX-102~~resources SL in the ~~U.S.~~launch ~~The regulatory approval and successful commercialization~~ of ~~TNX-102~~TONMYA. SLWe ishave ~~subject~~never, toas ~~many~~an ~~risks~~organization, ~~including those~~launched ~~discussed~~any in other ~~risk factors~~product, and ~~TNX-102~~there is SLno ~~may~~guarantee ~~not~~that ~~receive~~we ~~approval~~will ~~from~~be ~~the~~able ~~FDA.~~to Ifsuccessfully ~~the~~commercialize ~~results~~TONMYA. orThere ~~timing~~are ofnumerous ~~regulatory filings,~~examples ~~the~~of ~~regulatory~~failures ~~process,~~to ~~regulatory~~meet ~~developments,~~high expectations ~~commercialization,~~of ormarket ~~other activities~~potential, ~~actions~~including orby ~~decisions~~pharmaceutical ~~related to~~companies ~~TNX-102~~with SLmore doexperience ~~not~~and ~~meet~~resources ~~our~~than orus. ~~others’~~We ~~expectations,~~believe that the ~~market~~commercial ~~price~~success of ~~our~~TONMYA ~~common~~depends ~~stock~~on ~~could~~many ~~decline~~factors, ~~significantly.~~including the following:

67 ● the acceptance of TONMYA by physicians, patients and third-party payors;

~~The~~● ~~FDA assigned~~our aability ~~PDUFA~~to ~~goal~~effectively ~~date~~educate ofhealthcare ~~August~~providers ~~15,~~and ~~2025,~~patients ~~for a decision~~ on ~~marketing authorization for TNX-102 SL. and retains complete discretion in deciding whether to approve~~ the ~~NDA~~risks ~~for TNX-102 SL,~~ and ~~there~~clinical ~~are~~benefits ~~many components to an NDA filing beyond the efficacy and safety data provided to the FDA. No assurances can be given that the FDA will approve TNX-102 SL for the treatment~~ of ~~FM, or that if approved, we will successfully commercialize TNX-102 SL.~~TONMYA;

●

the efficacy, cost, approved use, and side-effect profile of TONMYA relative to competitive treatment regimens for fibromyalgia;

●

TONMYA may compete with the off-label use of currently marketed products and other therapies in development that may in the future obtain approval for fibromyalgia;

●

the effectiveness of our commercial strategy for the marketing of TONMYA, including our pricing strategy and the effectiveness of our efforts to obtain adequate third-party reimbursement;

●

developing, maintaining and successfully monitoring commercial manufacturing arrangements for TONMYA with third-party manufacturers to ensure they meet our standards and those of regulatory authorities, including the FDA, which extensively regulate and monitor pharmaceutical manufacturing facilities;

●

our ability to negotiate and enter into any additional commercial, supply and distribution contracts to support commercialization efforts, and to hire and manage additional qualified personnel;

●

our ability to meet the demand for commercial supplies of TONMYA at acceptable costs;

●

our ability to remain compliant with laws and regulations that apply to us and our commercial activities;

●

the actual market-size, ability to identify targeted patients and the demographics of patients eligible for TONMYA, which may be different than what we currently expect;

●

the occurrence of any side effects, adverse reactions or misuse, or any unfavorable publicity in these areas;

●

our ability to obtain, maintain or enforce our patents and other intellectual property rights; and

●

the effect of current and future health care legislation in the United States.

While we believe that TONMYA has a commercially competitive profile, we cannot accurately predict the amount of time needed to attain a commercially successful profile or the amount of revenue that would be generated from sales of TONMYA, and there is no guarantee that we will be able to maintain or increase product sales for TONMYA or any of our marketed products. While we have established our commercial team and hired our U.S. sales force, we will need to further expand and develop the team in order to continue to grow the business. Even if we are successful in developing our commercial team, there are many factors that could negatively impact sales of our marketed products or cause commercialization efforts to be unsuccessful, including several factors that are outside our control. If the continued commercialization of our marketed products or future sales are less successful than expected or perceived as disappointing, our stock price could decline significantly, and our long-term success company could be harmed.

We have a limited operating history and only recently launched TONMYA in the United States, which may make it difficult to evaluate the prospects for our future viability.

We are still in the relatively early stages of our transition from a clinical-stage to a commercial-stage company. Our operations to date have been primarily limited to conducting research and development activities, including preclinical studies and clinical trials and, more recently, commercializing our migraine products and launching TONMYA. We have not yet demonstrated an ability to generate significant revenues, or to conduct sales and marketing activities on a long-term sustained basis necessary for successful product commercialization. Initial sales of TONMYA may not be predictive of long-term commercial results.

We may encounter unforeseen expenses, difficulties, complications, delays and other known or unknown factors in achieving our business objectives. Accordingly, you should consider our prospects in light of the costs, uncertainties, delays and difficulties frequently encountered by companies in the early commercial stage, especially pharmaceutical companies such as ours. Any predictions about our future success or viability may not be as accurate as they could be if we had a longer operating history with these activities.

TONMYA and our migraine products remain subject to ongoing regulatory review, and if we fail to comply with continuing regulations, we could lose our approval and the sale of TONMYA or our migraine products could be suspended.

Even though we received FDA approval for TONMYA, the manufacturing, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion, sampling, and record keeping related to TONMYA and our migraine products will remain subject to extensive regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMP regulations, and GCPs for any clinical trials that we conduct post-approval, all of which may result in significant expense and limit our ability to commercialize TONMYA and our migraine products. As such, we and our contract manufacturers will be subject to periodic review and inspections to assess compliance with cGMP and adherence to commitments made in any NDA or other marketing application and previous responses to inspection observations. For certain commercial prescription drug products, manufacturers and other parties involved in the supply chain must also meet chain of distribution requirements and build electronic, interoperable systems for product tracking and tracing and for notifying the FDA of counterfeit, diverted, stolen and intentionally adulterated products or other products that are otherwise unfit for distribution in the United States. Accordingly, we and others with whom we work must continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing, production and quality control. The FDA may also require a REMS program for TONMYA or any future product candidates, which could include requirements for a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.

If we fail to comply with the regulatory requirements of the FDA and other applicable domestic and foreign regulatory authorities, or previously unknown problems with any of our marketed products, manufacturer, or manufacturing process are discovered, we could be subject to administrative or judicially imposed sanctions, including:

	●	restrictions on marketing or manufacturing;
	●	withdrawal of the product from the market;
	●	holds on clinical trials;
	●	warning letters or untitled letters;
	●	civil or criminal penalties;
	●	fines;
	●	injunctions;
	●	product seizures or detentions;
	●	pressure to initiate voluntary product recalls;
	●	suspension or withdrawal of regulatory approvals; and
	●	refusal to approve supplements to approved applications.

If any of these events occur, our ability to sell the affected product may be impaired, and we may incur substantial additional expense to comply with regulatory requirements, which could adversely affect our business, financial condition and results of operations.

If estimates of the size of the potential market for TONMYA are overstated or data we have used to identify prescribing healthcare providers is inaccurate, our ability to earn revenue to support our business could be materially adversely affected.

We have relied on external sources, including market research funded by us and third parties, and internal analyses and calculations to estimate the potential market opportunities for TONMYA. The externally sourced information used to develop these estimates has been obtained from sources we believe to be reliable, but we have not verified the data from such sources, and their accuracy and completeness cannot be assured. With respect to TONMYA, our internal analyses and calculations are based upon management’s understanding and assessment of numerous inputs and market conditions. These understandings and assessments necessarily require assumptions subject to significant judgment and may prove to be inaccurate. As a result, our estimates of the size of these potential market for TONMYA could prove to be overstated, perhaps materially.

In addition, we are relying on third-party data to identify the prescribers who treat the majority of fibromyalgia patients in the United States; however, we may not be marketing to the appropriate prescribers and may therefore be limiting our market opportunity.

Coverage and adequate reimbursement may not be available for our products, which could make it difficult for us to sell our products profitably.

Market acceptance and sales of our products depends in part on the extent to which reimbursement for these drugs and related treatments will be available from third-party payors, including government health administration authorities, pharmacy benefit managers (“PBMs”), managed care organizations and other private health insurers. Third-party payors decide which therapies they will pay for and establish reimbursement levels. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own coverage and reimbursement policies. However, decisions regarding the extent of coverage and amount of reimbursement to be provided for any drug is made on a payor-by-payor basis. If PBMs other payers or payer affiliates deny formulary inclusion, impose unfavorable tiering, or require burdensome utilization management restrictions, patient access to our products could be significantly limited. Moreover, one payor’s determination to provide coverage for a drug does not assure that other payors will also provide coverage, and adequate reimbursement, for the drug. Additionally, a third-party payor’s decision to provide coverage for a therapy does not imply that an adequate reimbursement rate will be approved. Each payor determines whether or not it will provide coverage for a therapy, what amount it will pay the manufacturer for the therapy, and on what tier of its formulary it will be placed. The position on a payor’s list of covered drugs, or formulary, generally determines the co-payment that a patient will need to make to obtain the therapy and can strongly influence the adoption of such therapy by patients and physicians. Patients who are prescribed treatments for their conditions and providers prescribing such services generally rely on third-party payors to reimburse all or part of the associated healthcare costs. Patients are unlikely to use our drugs unless coverage is provided and reimbursement is adequate to cover a significant portion of the cost of our drugs.

A primary trend in the U.S. healthcare industry and elsewhere is cost containment. Third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. We cannot be sure that coverage and reimbursement will be available or continue to be available for any drug that we commercialize and, if reimbursement is available, what the level of reimbursement will be. Inadequate coverage and reimbursement may impact the demand for, or the price of, any drug we commercialize. If coverage and adequate reimbursement are not available, or are available only to limited levels, we may not be able to successfully commercialize our current and any future drug products.

Access to prescription drugs in the U.S. commercial market is largely controlled by three dominant entities: Emisar/Optum/United HealthCare, Ascent/Express Scripts/Cigna, and Zinc/CVS Caremark/Aetna, which collectively manage a significant portion of formulary decisions and reimbursement policies. These entities have the ability to deny or restrict formulary access to our products through various techniques, including National Drug Code (“NDC”) blocks, exclusion lists, and unfavorable tier placement. Such actions could severely limit patient access to our therapies, reduce sales, and negatively impact our financial performance. Additionally, the consolidation of PBMs and insurers further strengthens their negotiating leverage, increasing the risk of unfavorable pricing and reimbursement terms for our products.

Moreover, PBMs have significant influence over prescription drug access through formulary decisions, reimbursement policies, and utilization management practices. In some cases, PBMs may prioritize lower-cost alternatives, including off-label or unapproved therapies, over our FDA-approved products. This could include steering patients toward opioid-based treatments for fibromyalgia or barbiturates for migraine or other medications that do not meet the same regulatory and safety standards as our products. Such actions may limit patient access to clinically appropriate therapies and negatively impact our sales.

Healthcare legislative or regulatory reform measures, including government restrictions on pricing and reimbursement, may have a negative impact on our business and results of operations.

In the United States and some foreign jurisdictions, there have been, and continue to be, several legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing authorization of product candidates, restrict or regulate post-approval activities, and affect our ability to profitably sell any of our commercialized products.

Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives. For example, in the United States, the ~~PPACA~~Patient Protection and Affordable Care Act (“ACA”), as supplemented by the Inflation Reduction Act of 2022 (“IRA”) and presidential executive orders, substantially changed the way healthcare is financed by both the government and private insurers, and significantly affects the pharmaceutical industry. Many provisions of the ACA impact the biopharmaceutical industry, including that in order for a biopharmaceutical product to receive federal reimbursement under the Medicare Part B and Medicaid programs or to be sold directly to U.S. government agencies, the manufacturer must extend discounts to entities eligible to participate in the drug pricing program under the Public Health Services Act, or PHS.

68Additionally, the IRA, which is subject to active modification efforts, includes policies that have a direct impact on drug prices and reduced drug spending by the federal government. This legislation contains substantial drug pricing reforms, including the establishment of a drug price negotiation program within the U.S. Department of Health and Human Services that requires manufacturers to charge a negotiated “maximum fair price” for certain selected drugs covered by Medicare or pay an excise tax for noncompliance, rebate payment requirements on manufacturers of certain drugs payable under Medicare Parts B and D to penalize price increases that outpace inflation, and required discounts on Part D drugs. Moreover, presidential executive orders and agency guidance may rapidly change reimbursement and pricing conditions.

Additionally, the Inflation Reduction Act of 2022 includes policies that are designed to have a direct impact on drug prices and reduce drug spending by the federal government. This legislation contains substantial drug pricing reforms, including the establishment of a drug price negotiation program within the U.S. Department of Health and Human Services that would require manufacturers to charge a negotiated “maximum fair price” for certain selected drugs covered by Medicare or pay an excise tax for noncompliance, the establishment of rebate payment requirements on manufacturers of certain drugs payable under Medicare Parts B and D to penalize price increases that outpace inflation, and requires manufacturers to provide discounts on Part D drugs.

Legislative, administrative, and private payor efforts to control drug costs span a range of proposals, including drug price negotiation, Medicare Part D redesign, drug price inflation rebates, international mechanisms, generic drug promotion and anticompetitive behavior, manufacturer reporting, and reforms that could impact therapies utilizing the accelerated approval pathway. We cannot predict the ultimate content, timing or effect of any changes to the ACA, the Inflation Reduction Act, or other federal and state healthcare policy reform efforts including those aimed at drug pricing. There is no assurance that federal or state health care reform will not adversely affect our future business and financial results, and we cannot predict how future federal or state legislative, judicial or administrative changes relating to healthcare policy will affect our business.

At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price orand patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Other examples of proposed and recent changes include, but are not limited to, expanding post-approval requirements, changing the Orphan Drug Act, ~~and~~ restricting sales and promotional activities for pharmaceutical products, enacting drug price transparency laws, and the creation of prescription drug affordability boards with authority to review and, in some cases, constrain, payment levels.

We cannot be sure whether additional legislative or administrative changes will be enacted, or whether government regulations, guidance or interpretations will be changed, or what the impact of such changes would be on the marketing approvals, sales, pricing, or reimbursement of our drug candidates or products, if any, may be. We expect that these and other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we receive for any approved drug. Any reduction in reimbursement from Medicare or other government programs may result in a similar ~~reduction~~ reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our drugs.

In addition, FDA regulations and guidance may be revised or reinterpreted by the FDA in ways that may significantly affect our business and our products. Any new regulations or guidance, or revisions or reinterpretations of existing regulations or guidance, may impose additional costs or lengthen FDA review times for our product candidates. We cannot determine how changes in regulations, statutes, policies, or interpretations when and if issued, enacted or adopted, may affect our business in the future. Such changes could, among other things, require: 65

In addition, FDA regulations and guidance may be revised or reinterpreted by the FDA in ways that may significantly affect our business and our products. Any new regulations or guidance, or revisions or reinterpretations of existing regulations or guidance, may impose additional costs or lengthen FDA review times for our product candidates. Moreover, ongoing policy focus on accelerated approval oversight and facilitating the introduction of generics and biosimilars could tighten post-marketing obligations and increase competitive pressure on reference products. We cannot determine how changes in regulations, statutes, policies, or interpretations when and if issued, enacted or adopted, may affect our business in the future. Such changes could, among other things, require:

●

additional clinical trials to be conducted prior to obtaining approval;

● changes to manufacturing methods; ~~● recalls, replacements, or discontinuance of one or more of our products; and~~

●

increased competition;

●

recalls, replacements, or discontinuance of one or more of our products; and

●

additional recordkeeping.

Such changes would likely require substantial time and impose significant costs, or could reduce the potential commercial value of our product candidates. In addition, delays in receipt of or failure to receive regulatory clearances or approvals for any other products would harm our business, financial condition, and results of operations.

Even if we obtain regulatory approval to market our product candidates, our product candidates may not be accepted by the market.

Even if the FDA approves one or more of our product candidates, physicians and patients may not accept it or use it. Even if physicians and patients would like to use our products, our products may not gain market acceptance among healthcare payors such as managed care formularies, insurance companies or government programs such as Medicare or Medicaid. Acceptance and use of our products will depend upon a number of factors including: perceptions by members of the health care community, including physicians, about the safety and effectiveness of our drug or device product; cost-effectiveness of our product relative to competing products; availability of reimbursement for our product from government or other healthcare payors; and effectiveness of marketing and distribution efforts by us and our licensees and distributors, if any.

The degree of market acceptance of any pharmaceutical product that we develop will depend on a number of factors, including:

● cost-effectiveness; ● the safety and effectiveness of our products, including any significant potential side effects (including drowsiness and dry mouth), as compared to alternative products or treatment methods; ● the timing of market entry as compared to competitive products; ● the rate of adoption of our products by doctors and nurses; ● product labeling or product insert required by the FDA for each of our products; ● reimbursement policies of government and third-party payors; ● effectiveness of our sales, marketing and distribution capabilities and the effectiveness of such capabilities of our collaborative partners, if any; and ● unfavorable publicity concerning our products or any similar products.

~~Because we~~● ~~expect~~the ~~sales~~safety and effectiveness of our ~~current~~ product candidates, ifincluding ~~approved,~~any tosignificant ~~generate~~potential ~~substantially~~side ~~all~~effects ofas ~~our~~compared ~~product~~to ~~revenues~~alternative ~~for the foreseeable future, the failure of these~~ products toor ~~find~~treatment ~~market acceptance would harm our business and could require us to seek additional financing.~~methods;

70● the timing of market entry as compared to competitive products;

~~Our~~● ~~prospects are dependent on~~ the ~~continued successful~~rate ~~commercialization~~ of ~~Zembrace~~adoption ~~and Tosymra. To the extent we cannot maintain or increase sales~~ of ~~Zembrace and Tosymra,~~ our ~~business,~~ ~~financial~~products ~~condition~~by ~~and~~doctors ~~results of operations may be materially adversely affected~~ and ~~the price of our common stock may decline.~~nurses;

~~Zembrace~~● ~~and~~product ~~Tosymra~~labeling ~~are our only drugs that have been approved for sale. Continued commercialization of Zembrace and Tosymra is subject to many risks, and there is no guarantee that we will be able to maintain~~ or ~~increase~~product ~~sales~~insert ofrequired ~~Zembrace~~by ~~and Tosymra. While we have established our commercial team and have hired our U.S. sales force, we will need to further expand and develop~~ the ~~team~~FDA infor ~~order~~each ~~to continue to successfully grow the business. Even if we are successful in developing our commercial team, there are many factors that could negatively impact sales~~ of ~~Zembrace and Tosymra or cause the continued commercialization of Zembrace and Tosymra to be unsuccessful, including several factors that are outside~~ our control. If the continued commercialization of Zembrace and Tosymra or future sales are less successful than expected or perceived as disappointing, our stock price could decline significantly, and the long-term success of the product and our company could be harmed.products;

~~Additionally,~~● ~~our~~reimbursement ~~strategy~~policies ~~in the U.S. includes distributing Zembrace and Tosymra solely through a limited network~~ of ~~third-party~~government ~~specialty distributors~~ and specialty pharmacies. While we have entered into agreements with each of these distributors and pharmacies to distribute Zembrace and Tosymra in the U.S., they may not perform as agreed or they may terminate their agreements with us. Also, we may need to enter into agreements with additional distributors or pharmacies, and there is no guarantee that we will be able to do so on commercially reasonable terms or at all. In the event we are unable to maintain, or expand, if needed, our commercial team, including our U.S. sales force, or maintain and, if needed, expand, our network of third-party ~~specialty distributors and specialty pharmacies, our ability to continue commercializing Zembrace and Tosymra would be limited, and Zembrace and Tosymra may not be profitable.~~ payors;

We● ~~have~~effectiveness aof ~~history~~our ofsales, ~~operating~~marketing ~~losses~~ and ~~expect~~distribution tocapabilities ~~incur~~and ~~losses~~the ~~for~~effectiveness ~~the~~of ~~foreseeable~~such ~~future.~~capabilities Weof ~~may~~our ~~never~~collaborative ~~achieve~~partners, ~~profitability.~~if any; and

We● ~~are~~unfavorable ~~focused~~publicity onconcerning ~~product development, and we started generating revenues from product sales in the third quarter of 2023. We have incurred losses in each year of~~ our ~~operations,~~products ~~and~~or weany ~~expect~~similar ~~to continue to incur operating losses for the foreseeable future~~products. ~~These operating losses have adversely affected and are likely to continue to adversely affect our working capital, total assets and shareholders’ equity.~~

~~We and our prospects~~Because should be examined in light of the risks and difficulties frequently encountered by new and early-stage companies in new and rapidly evolving markets. These risks include, among other things, the speed at which we ~~can~~expect ~~scale~~sales ~~up operations, our complete dependence upon development~~ of our current product candidates, ~~that~~if ~~currently have no market acceptance~~approved, ~~our ability~~ to ~~establish~~generate ~~and~~product ~~expand our brand name~~revenues, ~~our~~the ~~ability~~failure toof ~~expand~~these ~~our~~products ~~operations~~ to find ~~meet~~market ~~the~~acceptance ~~commercial~~would ~~demand~~harm of our ~~clients,~~business ~~our development of~~ and ~~reliance~~could onrequire ~~strategic and~~us ~~customer relationships and our ability~~ to ~~minimize~~seek ~~fraud~~additional ~~and other security risks~~financing.

~~The process of developing~~Uncertainty ~~our~~in ~~products~~Government ~~requires~~funding ~~significant clinical, nonclinical~~ and ~~CMC~~in-kind ~~development,~~support ~~laboratory~~policies ~~testing~~ and ~~clinical~~programs ~~studies.~~may Inadversely ~~addition, commercialization~~affect of our product candidates will require that we obtain necessary regulatory approvals and establish sales, marketing and manufacturing capabilities, either through internal hiring or through contractual relationships with othersbusiness. We expect to incur substantial losses for the foreseeable future as a result of anticipated increases in our research and development costs, including costs associated with conducting preclinical and nonclinical testing and clinical studies, and regulatory compliance activities.

~~We expect to incur~~Changes ~~substantial~~in ~~additional~~federal ~~operating~~funding ~~expenses~~policies, ~~over~~including the ~~next~~ongoing ~~several~~review ~~years~~of asDoD ~~our~~contracts ~~research,~~and ~~development,~~NIH ~~preclinical~~grants and ~~nonclinical testing,~~in-kind ~~and~~support ~~clinical~~by ~~study~~the ~~activities~~current ~~increase~~administration, could ~~and~~impact ifour financial resources and ~~when~~the weprogress ~~acquire~~of ~~rights~~research toconducted ~~additional~~with ~~product~~U.S.-based ~~candidates~~university collaborators. ~~The~~While we ~~amount~~have ofsecured ~~future~~certain ~~losses~~DoD and ~~when,~~NIH iffunding ~~ever,~~and weNIH ~~will~~in-kind ~~achieve~~support ~~profitability~~through ~~are~~Project ~~uncertain.~~NextGen, Wethere ~~have~~is ~~two~~no ~~products~~guarantee that ~~have~~such ~~generated~~funding ~~commercial~~or ~~revenue starting~~ in-kind ~~the~~support ~~third~~will ~~quarter~~not ofbe ~~2023,~~rescinded ~~but~~or weotherwise dorestricted, ~~not~~particularly ~~expect~~as ~~revenues from~~ the ~~commercial~~Biomedical ~~sale~~Advanced ofResearch ~~products~~and toDevelopment ~~exceed~~Authority ~~expenses~~(“BARDA”) inhas ~~the~~begun ~~near~~withdrawing ~~future.~~or ~~Our~~terminating ~~ability~~some toProject ~~generate~~NextGen-related ~~revenue~~awards. ~~and achieve profitability will depend on~~Additionally, ~~among other things~~DoD, ~~successful~~NIH ~~completion~~and ofBARDA ~~the~~funding ~~development~~for any of our ~~product~~future ~~candidates;~~projects ~~obtaining~~may ~~necessary~~be ~~regulatory approvals from the FDA; establishing manufacturing~~delayed, ~~sales~~reduced, ~~and~~or ~~marketing~~denied ~~arrangements~~altogether. ~~with~~Any ~~third~~such ~~parties;~~changes ~~successfully~~could ~~commercializing~~adversely affect our ~~products;~~research ~~establishing~~programs, ~~a favorable~~financial ~~competitive~~condition, ~~position;~~ and ~~raising~~operational ~~sufficient funds to finance our activities~~plans. ~~Many~~Further, ofcertain ~~these~~research ~~factors~~projects ~~will~~conducted ~~depend~~in ~~on circumstances~~collaboration ~~beyond~~with ~~our control~~U. ~~We might not succeed at any of these undertakings~~S.-based Ifuniversity wecollaborators ~~are~~could ~~unsuccessful~~be atslowed ~~some~~ or ~~all of these undertakings, our business, prospects, and results of operations may be materially adversely affected~~discontinued.

71 66

~~We expect a number of factors to~~RISKS ~~cause~~RELATED ~~our~~TO ~~operating~~PRODUCT ~~results~~DEVELOPMENT, toREGULATORY ~~fluctuate on a quarterly and annual basis~~APPROVAL, ~~which~~MANUFACTURING ~~may~~AND ~~make it difficult to predict our future performance.~~COMMERCIALIZATION

We have not yet obtained regulatory approvals for TNX-102 SL or any of our other product candidates. Consequently, any predictions made about our future success or viability may not be as accurate as they could be if we had a longer operating history or commercialized products. Our financial condition has varied significantly in the past and will continue to fluctuate from quarter-to-quarter or year-to-year due to a variety of factors, many of which are beyond our control. Factors relating to our business that may contribute to these fluctuations include other factors described elsewhere in this annual report and also include, among other things:

● our ability to obtain additional funding to develop our product candidates;

● market acceptance of our product candidates; ● the ability of patients or healthcare providers to obtain coverage of or sufficient reimbursement for our products; ● our ability to obtain and maintain regulatory approval for our product candidate TNX-102 SL for FM, or any of our other product candidates in the United States and foreign jurisdictions;

● delays in the commencement, enrollment and timing of clinical studies;

● the success of our clinical studies through all phases of clinical development, including studies of our most advanced product candidate, TNX-102 SL for FM and potentially other CNS indications;

● any delays in regulatory review and approval of product candidates in clinical development;

● potential nonclinical toxicity and/or side effects of our product candidates that could delay or prevent commercialization, limit the indications for any approved drug, require the establishment of REMS, or cause an approved drug to be taken off the market;

● our ability to establish or maintain collaborations, licensing or other arrangements;

● competition from existing products or new products that may emerge;

● our ability to leverage our proprietary technology platform to discover and develop additional product candidates;

● our ability and our licensors’ abilities to successfully obtain, maintain, defend and enforce intellectual property rights important to our business; and

● potential product liability claims;

Accordingly, the results of any quarterly or annual periods should not be relied upon as indications of future operating performance.

Uncertainty in Government Funding and In-Kind Support Policies and Programs may adversely affect our business.

Changes in federal funding policies, including the ongoing review of DoD contracts and NIH grants and in-kind support by the new administration of President Donald Trump, could materially impact our financial resources and the progress of research conducted with U.S.-based university collaborators. While we have secured certain DoD and NIH funding and NIH in-kind support through Project NextGen, there is no guarantee that such funding or in-kind support will not be rescinded or otherwise restricted. Additionally, DoD, NIH and Biomedical Advanced Research and Development Authority (“BARDA”) funding for future projects may be delayed, reduced, or denied altogether. Any such changes could adversely affect our research programs, financial condition, and operational plans. Further, certain research projects conducted in collaboration with U.S.-based university collaborators could be slowed or discontinued.

We are exposed to cybersecurity and data privacy risks that, if realized, could expose us to legal liability, damage our reputation and harm our business.

We face risks of cyber-attacks, computer hacks, theft, viruses, malicious software, phishing, employee error, denial-of-service attacks and other security breaches that could jeopardize the performance of our software and expose us to financial and reputational harm. Any of these occurrences could create liability for us, put our reputation in jeopardy and harm our business. Such harm could be in the form of theft of our or our customers’ confidential information, the inability to access our systems. In some cases, we rely on the safeguards put in place by third parties to protect against security threats. These third parties, including vendors that provide products and services for our operations, could also be a source of security risk to us in the event of a failure or a security incident affecting their own security systems and infrastructure. Our network of partners could also be a source of vulnerability to the extent their applications interface with ours, whether unintentionally or through a malicious backdoor. We do not review the software code included in third-party integrations in all instances. Because the techniques used to obtain unauthorized access or to sabotage systems change frequently and generally are not recognized until launched against a target, we or these third parties may be unable to anticipate these techniques or to implement adequate preventative measures. We have internal controls designed to prevent cyber-related frauds related to authorizing the transfer of funds, but such internal controls may not be adequate. With the increasing frequency of cyber-related frauds to obtain inappropriate payments and other threats related to cyber-attacks, we may find it necessary to expend resources to remediate cyber-related incidents or to enhance and strengthen our cybersecurity. Our remediation efforts may not be successful and could result in interruptions, delays or cessation of service. Although we have insurance coverage for losses associated with cyber-attacks, as with all insurance policies, there are coverage exclusions and limitations, and our coverage may not be sufficient to cover all possible claims, and we may still suffer losses that could have a material adverse effect on our reputation and business.

The increase in remote working arrangements by our employees, vendors, and other third parties also increase the risk of a data security compromise and the possible attack surfaces. Although we conduct training as part of our information security, cybersecurity, and data privacy efforts, that training cannot be completely effective in preventing those attacks from being successful. There can be no assurance that our cybersecurity risk management program and processes, including our policies, controls, or procedures, will be fully implemented, complied with or effective in protecting our systems and information.

RISKS RELATED TO PRODUCT DEVELOPMENT, REGULATORY APPROVAL, MANUFACTURING AND COMMERCILAIZATION

Our product candidates are novel and still in development.

Our drug development ~~methods~~activities may not lead to commercially viable drugs for any of several reasons. For example, we may fail to identify appropriate targets or compounds, our drug candidates may fail to be safe and effective in clinical studies, or we may have inadequate financial or other resources to pursue development efforts for our drug candidates. Our drug candidates will require significant additional development, clinical studies, regulatory clearances and additional investment by us or our collaborators before they can be commercialized.

Further, we and our product candidates are subject to extensive regulation by the FDA and comparable regulatory authorities in other countries governing, among other things, research, testing, clinical studies, manufacturing, labeling, promotion, selling, adverse event reporting and recordkeeping. We are not permitted to market any of our product candidates in the United States until we receive approval of an NDA for a product candidate from the FDA or the equivalent approval from a foreign regulatory authority. Obtaining FDA approval is a lengthy, expensive and uncertain process. The success of our business depends on the successful development, approval and commercialization of our product candidates. Any projected sales or future revenue predictions are predicated upon FDA approval and market acceptance. If projected sales do not materialize for any reason, it would have a material adverse effect on our business and our ability to continue operations.

To obtain revenues from sales of our product candidates, we must succeed, either alone or with third parties, in developing, obtaining regulatory approval for, manufacturing and marketing drugs with commercial potential. We may never succeed in these activities, and we may not generate sufficient revenues to continue our business operations or achieve profitability.

Successful development of our products is uncertain.

Our development of current and future product candidates is subject to the risks of failure and delay inherent in the development of new pharmaceutical products, including: delays in product development, clinical testing, or manufacturing; unplanned expenditures in product development, clinical testing, or manufacturing; failure to receive regulatory approvals; emergence of superior or equivalent products; inability to manufacture on our own, or through any others, product candidates on a commercial scale; and failure to achieve market acceptance.

Because of these risks, our research and development efforts may not result in any commercially viable products. If a significant portion of these development efforts are not successfully completed, required regulatory approvals are not obtained or any approved products are not commercially successfully, our business, financial condition, and results of operations may be materially harmed.

If preclinical and nonclinical testing or clinical studies for our product candidates are unsuccessful or delayed, we will be unable to meet our anticipated development and commercialization timelines.

We rely and expect to continue to rely on third parties, including contract research organizations, or CROs, and outside consultants, to conduct, supervise or monitor some or all aspects of preclinical and nonclinical testing and clinical studies involving our product candidates. We have less control over the timing and other aspects of these preclinical and nonclinical testing activities and clinical studies than if we performed the monitoring and supervision entirely on our own. Third parties may not perform their responsibilities for our preclinical and nonclinical testing and clinical studies on our anticipated schedule or, for clinical studies, consistent with a clinical study protocol. Delays in preclinical and nonclinical testing, and clinical studies could significantly increase our product development costs and delay product commercialization. In addition, many of the factors that may cause, or lead to, a delay in the clinical studies may also ultimately lead to denial of regulatory approval of a product candidate.

The commencement of clinical studies can be delayed for a variety of reasons, including delays in:

●

demonstrating sufficient safety and efficacy to obtain regulatory approval to commence a clinical study;

●

reaching agreement on acceptable terms with prospective CROs and study sites;

●

developing a stable formulation of a product candidate;

●

manufacturing sufficient quantities of a product candidate; and

●

obtaining institutional review board, or IRB, approval to conduct a clinical study at a prospective site.

Once a clinical study has begun, it may be delayed, suspended or terminated by us or the FDA or other regulatory authorities due to a number of factors, including:

●

ongoing discussions with the FDA or other regulatory authorities regarding the scope or design of our clinical studies;

●

failure to conduct clinical studies in accordance with regulatory requirements;

●

lower than anticipated recruitment or retention rate of patients in clinical studies;

●

inspection of the clinical study operations or study sites by the FDA or other regulatory authorities resulting in the imposition of a clinical hold;

●

lack of adequate funding to continue clinical studies;

●

negative results of clinical studies;

●

investigational drug product out-of-specification; or

●

nonclinical or clinical safety observations, including adverse events and SAEs.

If clinical studies are unsuccessful, and we are not able to obtain regulatory approvals for our product candidates under development, we will not be able to commercialize these products, and therefore may not be able to generate sufficient revenues to support our business.

We are subject to extensive and costly government regulation.

Product candidates employing our technology are subject to extensive and rigorous domestic government regulation including regulation by the FDA, the Centers for Medicare and Medicaid Services, other divisions of the United States Department of Health and Human Services, the United States Department of Justice, state and local governments, and their respective foreign equivalents. The FDA regulates the research, development, preclinical and nonclinical testing and clinical studies, manufacture, safety, effectiveness, record-keeping, reporting, labeling, storage, approval, advertising, promotion, sale, distribution, import, and export of biopharmaceutical products. The FDA regulates small molecule chemical entities as drugs, subject to an NDA under the FDCA. The FDA applies the same standards for biologics, requiring an IND application, followed by a Biologic License Application, or BLA, prior to licensure. Other products, such as vaccines, are also regulated under the Public Health Service Act. FDA has conflated the standards for approval of NDAs and BLAs so that they require the same types of information on safety, effectiveness, and CMCs. If products employing our technologies are marketed abroad, they will also be subject to extensive regulation by foreign governments, whether or not they have obtained FDA approval for a given product and its uses. Such foreign regulation may be equally or more demanding than corresponding United States regulation.

Government regulation substantially increases the cost and risk of researching, developing, manufacturing, and selling our products. The regulatory review and approval process, which includes preclinical and nonclinical testing and clinical studies of each product candidate, is lengthy, expensive, and uncertain. We or our collaborators must obtain and maintain regulatory authorization to conduct clinical studies. We or our collaborators must obtain regulatory approval for each product we intend to market, and the manufacturing facilities used for the products must be inspected and meet legal requirements. Securing regulatory approval requires the submission of extensive preclinical, nonclinical and clinical data and other supporting information for each proposed therapeutic indication in order to establish the product’s safety and efficacy, and in the case of biologics also potency and purity, for each intended use. The development and approval process takes many years, requires substantial resources, and may never lead to the approval of a product.

Even if we are able to obtain regulatory approval for a particular product, the approval may limit the indicated medical uses for the product, may otherwise limit our ability to promote, sell, and distribute the product, may require that we conduct costly post-marketing surveillance, and/or may require that we conduct ongoing post-marketing studies. Material changes to an approved product, such as, for example, manufacturing changes or revised labeling, may require further regulatory review and approval. Once obtained, any approvals may be withdrawn, including, for example, if there is a later discovery of previously unknown problems with the product, such as a previously unknown safety issue.

If we, our collaborators, or our CMOs fail to comply with applicable regulatory requirements at any stage during the regulatory process, such noncompliance could result in, among other things, delays in the approval of applications or supplements to approved applications; refusal of a regulatory authority, including the FDA, to review pending market approval applications or supplements to approved applications; warning letters; fines; import and/or export restrictions; product recalls or seizures; injunctions; total or partial ~~suspension~~ suspension of production; civil penalties; withdrawals of previously approved marketing applications or licenses; recommendations by the FDA or other regulatory authorities against governmental contracts; and/or criminal prosecutions.

We do not have, and may never obtain, the regulatory approvals we need to market our product candidates.

Following completion of clinical studies, the results are evaluated and, depending on the outcome, submitted to the FDA in the form of an NDA or BLA in order to obtain FDA approval of the product and authorization to commence commercial marketing. In responding to an NDA, the FDA may require additional testing or information, may require that the product labeling be modified, may impose post-approval study and other commitments or reporting requirements or other restrictions on product distribution, or may deny the application. The FDA has established performance goals for review of NDAs or BLAs: six months for priority applications and ten months for standard applications. However, the FDA is not required to complete its review within these time periods. The timing of final FDA review and action varies greatly but can take years in some cases and may involve the input of an FDA advisory committee of outside experts. Product sales in the United States may commence only when an NDA or BLA is approved.

To date, we have not received the regulatory approvals required for the commercial sale of any of our products in the United States or in any foreign jurisdiction. None of our product candidates have been determined to be safe and effective, and we have not submitted an NDA or BLA equivalent application to any foreign regulatory authorities for any of our product candidates.

It is possible that none of our product candidates will be approved for marketing. Failure to obtain regulatory approvals, or delays in obtaining regulatory approvals, may adversely affect the successful commercialization of any drugs or biologics that we or our partners develop, may impose additional costs on us or our collaborators, may diminish any competitive advantages that we or our partners may attain, and/or may adversely affect our receipt of revenues or royalties.

Our product candidates may cause serious adverse events, or SAEs, or undesirable side effects which may delay or prevent marketing authorization, or, if approval is received, require them to be taken off the market, require them to include safety warnings or otherwise limit their sales.

SAEs or undesirable side effects from any of our other product candidates could arise either during clinical development or, if approved, after the approved product has been marketed. The results of future clinical studies may show that our product candidates cause SAEs or undesirable side effects, which could interrupt, delay or halt clinical studies, resulting in delay of, or failure to obtain, marketing authorization from the FDA and other regulatory authorities.

If any of our ~~other~~ product candidates cause SAEs or undesirable side effects or suffer from quality control issues:

●

regulatory authorities may impose a clinical hold or risk evaluation and mitigation strategies, or REMS, which could result in substantial delays, significantly increase the cost of development, and/or adversely impact our ability to continue development of the product;

●

regulatory authorities may require the addition of statements, specific warnings, or contraindications to the product label, or restrict the product’s indication to a smaller potential treatment population;

●

we may be required to change the way the product is administered or conduct additional clinical studies;

● we may be required to implement a risk minimization action plan, which could result in substantial cost increases and have a negative impact on our ability to commercialize the product; ~~● we may be required to limit the participants who can receive the product;~~

●

we may be required to limit the participants who can receive the product;

●

we may be subject to limitations on how we promote the product;

●

we may, voluntarily or involuntarily, initiate field alerts for product recall, which may result in shortages;

●

sales of the product may decrease significantly;

●

regulatory authorities may require us to take our approved product off the market;

●

we may be subject to litigation or product liability claims; and

●

our reputation may suffer.

Any of these events could prevent us from achieving or maintaining market acceptance of the affected product or could substantially increase commercialization costs and expenses, which in turn could delay or prevent us from generating significant revenues from the sale of our products.

If we are required to generate additional data related to safety and efficacy in order to obtain approval for TNX-SL for FM under Section 505(b)(2), we may be unable to meet our anticipated development and commercialization timelines.

We submitted the NDA for TNX-102 SL for FM under Section 505(b)(2) of the FDCA, which would enable us to rely in part on data in the public domain or elsewhere. Some of the data required by the FDA for approval may be related to products already approved by the FDA. If the data relied upon is related to products already approved by the FDA and covered by third-party patents, we would be required to certify that we do not infringe the listed patents or that such patents are invalid or unenforceable. As a result of the certification, the third-party would have 45 days from notification of our certification to initiate an action against us. In the event that an action is brought in response to such a certification, the approval of our NDA could be subject to a stay of up to 30 months or more while we defend against such a suit. Approval of our product candidates under Section 505(b)(2) may therefore be delayed until patent exclusivity expires or until we successfully challenge the applicability of those patents to our product candidates. Alternatively, we may elect to generate sufficient additional clinical data so that we no longer rely on data which triggers a potential stay of the approval of our product candidates. Even if no exclusivity periods apply to our applications under Section 505(b)(2), the FDA has broad discretion to require us to generate additional data on the safety and efficacy of our product candidates to supplement third-party data on which we may be permitted to rely. In either event, we could be required, before obtaining marketing authorization for any of our product candidates, to conduct substantial new research and development activities beyond those we currently plan to engage in order to obtain approval of our product candidates. Such additional new research and development activities would be costly and time-consuming.

The FDA may not approve our NDA based on their review of the submitted data. If cyclobenzaprine-containing products are withdrawn from the market by the FDA for any safety reason, we may not be able to reference such products to support a 505(b)(2) NDA for TNX-102 SL, and we may need to fulfill the more extensive requirements of Section 505(b)(1). If we are required to generate additional data to support approval, we may be unable to meet our anticipated development and commercialization timelines, may be unable to generate the additional data at a reasonable cost, or at all, and may be unable to obtain marketing authorization of our lead product candidate.

Any breakthrough, fast track or orphan drug designation or grant of priority review status by the FDA may not actually lead to a faster development or regulatory review or approval process, nor will it assure FDA approval of our product candidates. Additionally, our product candidates may treat indications that do not qualify for priority review vouchers.

If a product candidate offers major advances in treatment, the FDA may designate it eligible for priority review. The FDA has broad discretion whether or not to grant these designations, so even if we believe a particular product candidate is eligible for these designations, we cannot assure you that the FDA would decide to grant them. Even if we do receive fast track designation or priority review, we may not experience a faster development process, review or approval compared to conventional FDA procedures. The FDA may withdraw fast track designation if it believes that the designation is no longer supported by data from our clinical development program.

Even if approved, our product candidates will be subject to extensive post-approval regulation.

Once a product is approved, numerous post-approval requirements apply. Among other things, the holder of an approved NDA is subject to periodic and other FDA monitoring and reporting obligations, including obligations to monitor and report adverse events and instances of the failure of a product to meet the specifications in the NDA. Application holders must submit new or supplemental applications and obtain FDA approval for certain changes to the approved product, product labeling, or manufacturing process. Application holders must also submit advertising and other promotional material to the FDA and report on ongoing clinical studies.

Depending on the circumstances, failure to meet these post-approval requirements can result in criminal prosecution, fines, injunctions, recall or seizure of products, total or partial suspension of production, denial or withdrawal of pre-marketing product approvals, or refusal to allow us to enter into supply contracts, including government contracts. In addition, even if we comply with FDA and other requirements, new information regarding the safety or effectiveness of a product could lead the FDA to modify or withdraw product approval.

Our relationships with customers, physicians, and third-party payors is subject, to federal and state healthcare fraud and abuse laws, false claims laws, health information privacy and security laws, and other healthcare laws and regulations. If we are unable to comply, or have not fully complied, with such laws, we could face substantial penalties.

Healthcare providers, physicians and third-party payors in the United States and elsewhere will play a primary role in the recommendation and prescription of our products. Our current and future arrangements with healthcare professionals, principal investigators, consultants, customers and third-party payors subject us to various federal and state fraud and abuse laws and other health care laws, including, without limitation, the federal Anti-Kickback Statute, the federal civil and criminal false claims laws and the law commonly referred to as the Physician Payments Sunshine Act and regulations. These laws will impact, among other things, our clinical research, sales, marketing and educational programs. In addition, we may be subject to patient privacy laws by both the federal government and the states in which we conduct or may conduct our business. The laws that will affect our operations include, but are not limited to:

●

the federal Anti-Kickback Statute, which prohibits, among other things, persons or entities from knowingly and willfully soliciting, receiving, offering or paying any remuneration (including any kickback, bribe or rebate), directly or indirectly, overtly or covertly, in cash or in kind, in return for the purchase, recommendation, leasing or furnishing of an item or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs;

●

federal civil and criminal false claims laws, including, without limitation, the False Claims Act, and civil monetary penalty laws which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment or approval from Medicare, Medicaid or other government payors that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;

●

the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created new federal criminal statutes that prohibit a person from knowingly and willfully executing a scheme or making false or fraudulent statements to defraud any healthcare benefit program, regardless of the payor (e.g., public or private);

78● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, and as amended again by the final HIPAA omnibus rule, Modifications to the HIPAA Privacy, Security, Enforcement, and Breach Notification Rules Under HITECH and the Genetic Information Nondiscrimination Act; Other Modifications to HIPAA, published in January 2013, which imposes certain requirements relating to the privacy, security and transmission of individually identifiable health information without appropriate authorization by entities subject to the rule, such as health plans, health care clearinghouses and health care providers, and their respective business associates; additionally, several states have enacted comprehensive privacy and data protection laws that may apply to health related and consumer data, some of which may not be protected health information under HIPAA, and other jurisdictions, including, among others the EU and UK, include strict rules on processing personal data, cross border data transfers, and data subject rights, and may impose significant fines and corrective orders;

● ~~HIPAA,~~federal astransparency ~~amended~~laws, byincluding the ~~Health~~federal ~~Information~~Physician ~~Technology~~Payments ~~for~~Sunshine ~~Economic~~Act, ~~and~~which ~~Clinical~~is ~~Health~~part ~~Act~~of PPACA, orthat ~~HITECH,~~require ~~and~~certain ~~its~~manufacturers ~~implementing~~of ~~regulations~~drugs, devices, biologics and asmedical ~~amended~~supplies ~~again~~for bywhich ~~the~~payment ~~final~~is ~~HIPAA~~available ~~omnibus~~under ~~rule~~Medicare, ~~Modifications~~Medicaid toor the ~~HIPAA~~Children’s ~~Privacy,~~Health ~~Security,~~Insurance ~~Enforcement~~Program, ~~and~~with ~~Breach~~specific ~~Notification~~exceptions, ~~Rules~~to ~~Under~~report ~~HITECH~~annually ~~and~~to the ~~Genetic~~Centers ~~Information~~for ~~Nondiscrimination~~Medicare ~~Act;~~& ~~Other~~Medicaid ~~Modifications to HIPAA~~Services, ~~published~~or ~~in January 2013~~CMS, ~~which~~information ~~imposes~~related ~~certain requirements relating~~ to: ~~the~~(i) ~~privacy,~~payments ~~security~~or ~~and~~other ~~transmission~~“transfers of ~~individually~~value’’ ~~identifiable~~made ~~health~~to ~~information~~covered ~~without~~recipients, ~~appropriate~~including ~~authorization~~physicians, bycertain ~~entities~~non ~~subject~~physician topractitioners, ~~the~~and ~~rule,~~teaching ~~such~~hospitals; asand ~~health~~(ii) ~~plans,~~ownership ~~health~~and ~~care~~investment ~~clearinghouses~~interests ~~and~~held ~~health~~by ~~care~~covered ~~providers,~~recipients and their ~~respective~~immediate ~~business~~family ~~associates~~members;

● federal transparency laws, including the federal Physician Payments Sunshine Act, which is part of PPACA, that require certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services, or CMS, information related to: (i) payments or other “transfers of value’’ made to physicians and teaching hospitals; and (ii) ownership and investment interests held by physicians and their immediate family members;

●

state and foreign law equivalents of each of the above federal laws, state laws that require manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures, and state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or to adopt compliance programs as prescribed by state laws and regulations, or that otherwise restrict payments that may be made to healthcare providers; and

●

state and foreign laws that govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available, it is possible that some of our business activities could be subject to challenge under one or more of such laws.

It is possible that ~~governmental~~government authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, exclusion of drugs from government funded healthcare programs, such as Medicare and Medicaid, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws and the ~~curtailment~~ curtailment or restructuring of our operations.

The risk of our being found in violation of these laws is increased by the fact that many of them have not been fully interpreted by the regulatory authorities or the courts, ~~and~~ their provisions are open to a variety of interpretations, and they are subject to frequent policy changes. In addition, time-sensitive reporting and complex data aggregation requirements, and the need for ongoing training and monitoring create a shifting compliance environment. Efforts to ensure that our business ~~arrangements~~complies with ~~third parties will comply with~~ applicable healthcare laws and regulations ~~will~~involves ~~involve~~ substantial costs. Any action against us for violation of these laws, even if we successfully defend against it, could cause us to incur significant legal expenses and divert our management’s attention from the operation of our business. The shifting compliance environment and the need to build and maintain robust and expandable systems to comply with multiple jurisdictions with different compliance and/or reporting requirements increases the possibility that awe ~~healthcare company~~ may run afoul of one or more of the requirements.

If we obtain approval to commercialize any approved products outside of the United States, a variety of risks associated with international operations could materially adversely affect our business.

If ~~TNX-102~~TONMYA SL or any of our ~~other~~ product candidates ~~are~~is approved for commercialization outside of the United States, we intend to enter into agreements with third parties to market them on a worldwide basis or in more limited geographical regions. We expect that we will be subject to additional risks related to entering into international business relationships, including:

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different regulatory requirements for drug approvals;

Filing Compare · Tonix Pharmaceuticals Holding Corp.