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

For the transition period from to

Commission file number 001-34375

PLUS THERAPEUTICS, INC.

(Exact name of Registrant as Specified in Its Charter)

Delaware	33-0827593
(State or Other Jurisdiction ofIncorporation or Organization)	(I.R.S. EmployerIdentification No.)
2710 REED ROAD, SUITE 160, HOUSTON, TX	77051
6420 LEVIT GREEN BOULEVARD, SUITE 310, HOUSTON, TX	77021
(Address of principal executive offices)	(Zip Code)

Registrant’s telephone number, including area code: (737) 255-7194

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


Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, par value $0.001 per share	PSTV	Nasdaq Capital Market

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 in 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 Section 15(d) of the Exchange 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 every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 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 “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 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 common stock of the registrant held by non-affiliates of the registrant on June 2830, ~~2024~~2025, the last business day of the registrant’s most recently completed second fiscal quarter, was $831.29 million based on the closing sales price of the registrant’s common stock on June 2830, ~~2024~~2025 as reported on the Nasdaq Capital Market, of $10.4735 per share.

As of March 2110, ~~2025~~2026, there were 16171,~~999~~550,~~626~~698 shares of the registrant’s common stock issued and outstanding.

DOCUMENTS INCORPORATED BY REFERENCE:

Portions of the registrant’s definitive proxy statement for its ~~2025~~2026 Annual Meeting of Stockholders, which will be filed with the United States Securities and Exchange Commission within 120 days of December 31, ~~2024~~2025, are incorporated by reference into Part III of this Annual Report on Form 10-K.

Table of Contents

PLUS THERAPEUTICS, INC.

ANNUAL REPORT ON FORM 10-K FOR THE YEAR ENDED DECEMBER 31, ~~2024~~2025

TABLE OF CONTENTS

		Page
	PART I
Item 1.	Business	75
Item 1A.	Risk Factors	3026
Item 1B.	Unresolved Staff Comments	5753
Item IC.	Cybersecurity	5753
Item 2.	Properties	5854
Item 3.	Legal Proceedings	5854
Item 4.	Mine Safety Disclosures	5854
	PART II
Item 5.	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	5955
Item 6.	[Reserved]	5955
Item 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	6056
Item 7A.	Quantitative and Qualitative Disclosures About Market Risk	7469
Item 8.	Financial Statements and Supplementary Data	7570
Item 9.	Changes in and Disagreements with Accountants on Accounting and Financial Disclosure	~~102~~104
Item 9A.	Controls and Procedures	~~102~~104
Item 9B.	Other Information	~~102~~104
Item 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspection	~~103~~105
	PART III
Item 10.	Directors, Executive Officers and Corporate Governance	~~103~~105
Item 11.	Executive Compensation	~~103~~105
Item 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	~~103~~105

Item 13.	Certain Relationships and Related Transactions, and Director Independence	103
Item 14.	Principal Accounting Fees and Services	103
	PART IV
Item 15.	Exhibits, Financial Statement Schedules	104
Item 16.	Form 10-K Summary	104

Table of Contents


Item 13.	Certain Relationships and Related Transactions, and Director Independence	105
Item 14.	Principal Accounting Fees and Services	105

	PART IV

Item 15.	Exhibits, Financial Statement Schedules	106
Item 16.	Form 10-K Summary	106

Table of Contents

CAUTIONARY STATEMENT REGARDING FORWARD-LOOKING STATEMENTS

This report contains certain statements that may be deemed “forward-looking statements” within the meaning of U.S. securities laws, including statements regarding clinical trials, expected operations and upcoming developments. All statements, other than statements of historical fact, that address activities, events or developments that we intend, expect, project, believe or anticipate and similar expressions or future conditional verbs such as will, should, would, could or may occur in the future are forward-looking statements. Such statements are based upon certain assumptions and assessments made by our management in light of their experience and their perception of historical trends, current conditions, expected future developments and other factors they believe to be appropriate.

These statements include, without limitation, statements about our anticipated expenditures, including research and development, and general and administrative expenses; our intent or ability to regain and maintain compliance with Nasdaq listing standards; our strategic collaborations and license agreements, intellectual property, U.S. Food and Drug Administration and European Medicines Agency approvals and interactions and government regulation; the potential size of the market for our product candidates; our research and development efforts; results from our ~~pre-clinical~~preclinical and clinical studies and the implications of such results regarding the efficacy or safety of our product candidates; the safety profile, pathways, and efficacy of our product candidates and formulations; anticipated advantages of our product candidates over other products available in the market and being developed; the populations that will most benefit from our product candidates and indications that will be pursued with each product candidate; anticipated progress in our current and future clinical trials; plans and strategies to create novel technologies; our IP strategy; competition; future development and/or expansion of our product candidates and therapies in our markets; sources of competition for any of our product candidates; our pipeline; our ability to generate product or development revenue and the sources of such revenue; our ability to effectively manage our gross profit margins; our ability to obtain and maintain regulatory approvals; expectations as to our future performance; our ability to satisfy our obligations under the terms of our capital raising transactions including registering shares issuable in such transactions; portions of the “Liquidity and Capital Resources” section of this Annual Report on Form 10-K (“Form 10-K,”) including our potential need for additional financing and the availability thereof; our ability to integrate into our business and operations, develop, fully utilize and monetize acquired assets; our ability to continue as a going concern; our ability to ~~remain listed on The Nasdaq Capital Market; our ability to~~ repay or refinance some or all of our outstanding indebtedness and our ability to raise capital in the future; our ability to transfer the drug and medical device product manufacturing to a contract drug and medical device manufacturing organization; the potential enhancement of our cash position through development, marketing, and licensing arrangements; our ability to timely and efficiently launch our CNSide® Cerebrospinal Fluid Tumor Cell Enumeration test (the “CNSide Test”), and expand the CNSide platform for Immunocytochemistry (“ICC”), Fluorescence In Situ Hybridization (“FISH”) and Next Generation Sequencing (“NGS”); receipt of grant revenue; and a material security breach or cyber security attack affecting our operations and property. The forward-looking statements included in this report could differ materially from those expressed or implied by these forward-looking statements because of risks, uncertainties and other factors that include, but are not limited to, the risks described under ~~the “~~Risk ~~Factor Summary” and the “Risk~~ Factors” included below.

We encourage you to read the risks described under “Risk Factors” and elsewhere in this report carefully. We caution you not to place undue reliance on the forward-looking statements contained in this report. These statements, like all statements in this report, speak only as of the date of this report (unless an earlier date is indicated) and we undertake no obligation to update or revise any forward-looking statements to reflect events, trends or circumstances after the date they are made unless we have an obligation under U.S. federal securities laws to do so. Such forward-looking statements are not guarantees of future performance.

~~Risk~~Table ~~Factor~~of ~~Summary~~Contents

Below is a summary of the principal factors that may affect our business, financial condition, and results of operations. This summary does not address all of the risks that we face. Additional risks not currently known to us or that we currently deem to be immaterial also may materially adversely affect our business, financial condition or results of operations in future periods. Further discussion of the risks summarized in this risk factor summary, and other risks that we face, can be found below under the heading “Risk Factors” and should be carefully considered, together with other information in this Form 10-K and our other filings with the Securities and Exchange Commission (“SEC”).

Risks Related to Our Financial Position and Capital Requirements

We have incurred losses since inception, we expect to incur significant net losses in the foreseeable future and we may never become profitable and our operating results have been and will likely continue to be volatile.

Uncertainties relating to our ability to fund our operations for at least the next 12 months raises substantial doubt about our ability to continue as a going concern.

We could be delisted from Nasdaq for failure to comply with the minimum stockholders’ equity continued listing requirement or other applicable continued listing requirements and standards of Nasdaq, which would seriously harm the liquidity of our stock and our ability to raise capital.

We will need substantial additional funding to develop our product candidates and conduct our future operations and to repay our outstanding debt obligations. If we are unable to obtain the funds necessary to do so, we may be required to delay, scale back or eliminate our product development activities or may be unable to continue our business operations.

We maintain our cash at financial institutions, often in balances that exceed federally insured limits.

Risks Related to Our Business and Industry

If we fail to maintain proper and effective internal controls, our ability to produce accurate financial statements on a timely basis could be impaired.

Our future success is in large part dependent upon our ability to successfully develop our nanomedicine platform and commercialize REYOBIQ™ and 188RNL-BAM and any failure to do so could significantly harm our business and prospects.

188RNL-BAM will be regulated as a medical device, which may result in additional regulatory and other risks.

If we are unable to successfully partner with other companies to commercialize our product candidates, our business could materially suffer.

Our success depends in substantial part on our ability to obtain regulatory approvals for our RNL product candidates. However, we cannot be certain that we will receive regulatory approval for these product candidates or our other product candidates.

If we or any party to a key collaboration, licensing, development, acquisition or similar arrangement fail to perform material obligations, or commit a breach, under such arrangement, or any arrangement is terminated for any reason, there could be an adverse effect on our business.

Our current business strategy is high-risk and may not be successful.

Reliance on government funding for our programs may impose requirements that limit our ability to take certain actions, and subject it to potential financial penalties, which could materially and adversely affect our business, financial condition and results of operations.

If our competitors market or develop products that are marketed more effectively, approved more quickly than our product candidates, or demonstrated to be safer or more effective than our product candidates, our commercial opportunities could be reduced or eliminated.

Product development involves a lengthy and expensive process, with an uncertain outcome. We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates.

Pre-clinical studies and preliminary and interim data from clinical trials of our product candidates are not necessarily predictive of the results or success of ongoing or future clinical trials of our product candidates.

Because we have limited resources, we may decide to pursue a particular product candidate and fail to advance product candidates that later demonstrate a greater chance of clinical and commercial success.

Clinical trial results may fail to support approval of our product candidates.

We may have difficulty enrolling, or fail to enroll patients in our clinical trials, which could delay or prevent clinical trials of our drug candidates.

If a particular product candidate causes significant adverse events, then we may be unable to receive regulatory approval or market acceptance for such product candidate.

If our product candidates and technologies receive regulatory approval but do not achieve broad market acceptance, especially by physicians, the revenue that we generate will be limited.

All potential applications of our product candidates are investigational, which subjects us to development and marketing risks.

We and our product candidates are subject to extensive regulation, and the requirements to obtain regulatory approvals in the United States and other jurisdictions can be costly, time-consuming, and unpredictable. If we or our partners are unable to obtain timely regulatory approval for our product candidates, our business may be substantially harmed.

We will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant expense, and if we or our collaborators fail to comply with such requirements, regulatory agencies may take action against us or them, which could significantly harm our business.

Changing, new and/or emerging government regulations, including healthcare legislative reform measures, may adversely affect us.

Adequate coverage and reimbursement from third party payors may not be available for our product candidates, which could diminish our sales or adversely affect our ability to sell our products profitably.

Some intellectual property that we have in-licensed has been discovered through government funded programs and thus may be subject to federal regulations such as “march-in” rights, certain reporting requirements and a preference for U.S.-based companies. Compliance with such regulations may limit our exclusive rights, and limit our ability to contract with non-U.S. manufacturers.

Orphan drug designation may not ensure that we will enjoy market exclusivity in a particular market, and if we fail to obtain or maintain orphan drug designation or other regulatory exclusivity for some of our product candidates, our competitive position would be harmed.

If we experience an interruption in supply from a material sole source supplier, our business may be harmed.

We may engage in strategic transactions that could impact our liquidity, increase our expenses, and present significant distractions to our management.

We must maintain quality controls and compliance with manufacturing standards.

If we are unable to identify, hire and/or retain key personnel, we may not be able to sustain or grow our business.

We face potential product liability exposure, and if successful claims are brought against us, we may incur substantial liability if our insurance coverage for those claims is inadequate.

A failure to adequately protect health information could result in severe harm to our reputation and subject us to significant liabilities, each of which could have a material adverse effect on our business.

We and our collaborators must comply with environmental laws and regulations, including those pertaining to use of hazardous and biological materials in our business, and failure to comply with these laws and regulations could expose us to significant liabilities.

Risks Relating to Our Intellectual Property

Our success depends in part on our ability to protect our intellectual property.

We may not be able to protect our trade secrets.

We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.

We may incur substantial costs as a result of litigation or other proceedings relating to patent and other intellectual property rights, and we may be unable to protect our rights to our product candidates and technology.

If we are sued for infringing intellectual property rights of third parties, it will be costly and time consuming, and an unfavorable outcome in that litigation would have a material adverse effect on our business.

Risks Relating to the Issuance of Capital Stock, the Securities Markets and an Investment in Our Common Stock

Our stockholders may experience substantial dilution in the value of their investment if we issue additional shares of our capital stock.

Stockholders will suffer substantial dilution if certain provisions in the outstanding March 2025 Warrants are utilized.

There are a large number of shares of common stock underlying our outstanding Warrants and Prefunded Warrants and the sale of these shares may depress the market price of our common stock and cause immediate and substantial dilution to our existing stockholders.

The market price of our common stock may be volatile and fluctuate significantly, which could result in substantial losses for stockholders.

We may be or become the target of securities litigation, which is costly and time-consuming to defend.

We may issue debt and equity securities or securities convertible into equity securities, any of which may be senior to our common stock as to distributions and in liquidation, which could negatively affect the value of our common stock.

Our charter documents contain anti-takeover provisions.

We presently do not intend to pay cash dividends on our common stock.

If securities and/or industry analysts fail to continue publishing research about our business, if they change their recommendations adversely, or if our results of operations do not meet their expectations, our stock price and trading volume could decline.

PART I

Item 1. Business

References to “Plus Therapeutics,” the “Company,” “we,” “us” and “our” refer to Plus Therapeutics, Inc. References to “Notes” refer to the Notes to Financial Statements included herein (refer to Item 8).

General

Plus Therapeutics is a U.S. ~~pharmaceutical~~healthcare company developing ~~targeted~~and ~~radiotherapeutics~~commercializing ~~with~~precision ~~advanced~~diagnostics ~~platform~~and ~~technologies~~targeted radiopharmaceuticals for central nervous system (“CNS”) cancers. ~~Our~~CNSide ~~novel~~Diagnostics, ~~radioactive~~LLC ~~drug~~(“CNSide ~~formulations~~Diagnostics”) ~~and~~is ~~medical~~our ~~devices~~wholly owned subsidiary that develops and ~~therapeutic~~commercializes ~~candidates~~proprietary ~~are~~laboratory-developed tests, such as CNSide®, designed to ~~deliver~~identify ~~safe~~tumor ~~and~~cells ~~effective~~that ~~doses~~have ofmetastasized ~~radiation~~ to ~~tumors.~~the Tocentral ~~achieve~~nervous ~~this,~~system wein ~~have~~patients ~~developed~~with ~~innovative~~carcinomas ~~approaches~~and tomelanomas. ~~drug~~In ~~formulation~~radiopharmaceuticals, ~~including~~our ~~encapsulating~~lead ~~radionuclides~~candidate, ~~such as~~ rhenium ~~isotopes~~(186Re) ~~with~~obisbemeda, ~~nanoliposomes~~is ~~and~~designed ~~microspheres.~~specifically ~~Our~~for ~~formulations~~CNS ~~are~~cancers ~~intended~~including torecurrent ~~achieve~~glioblastoma ~~elevated~~(“GBM”), ~~patient-absorbed~~leptomeningeal ~~radiation~~metastases ~~doses~~(“LM”), and ~~extend~~pediatric ~~retention~~brain ~~times~~cancers ~~such~~(“PBC”) ~~that~~by ~~the~~direct ~~clearance~~localized delivery utilizing approved standard-of-care ~~the~~tissue ~~isotope~~access ~~occurs~~such ~~after~~as ~~significant~~with convection-enhanced delivery (“CED”) and ~~essentially~~intraventricular ~~complete~~brain ~~radiation~~(Ommaya ~~decay~~reservoir) catheters. Our acquired radiotherapeutic candidate, ~~which~~Rhenium-188 ~~will~~NanoLiposome ~~contribute~~Biodegradable ~~and~~Alginate ~~provide~~Microsphere ~~less~~(“188RNL-BAM”) ~~normal~~is ~~tissue/~~designed to treat many solid organ ~~exposure~~cancers including primary and ~~improved~~secondary ~~safety~~liver ~~margins~~cancers by intra-arterial injection.

Traditional approaches to radiation therapy for cancer, such as external beam radiation, have many disadvantages including continuous treatment for four to six weeks (which is onerous for patients), that the radiation damages healthy cells and tissue, and that the amount of radiation delivered is very limited and, therefore, is frequently inadequate to fully destroy the cancer.

Our ~~targeted~~novel ~~radiotherapeutic~~radioactive ~~platform~~drug ~~and~~formulations, ~~unique~~medical ~~investigational~~devices ~~drugs~~and therapeutic candidates have the potential to overcome these disadvantages byas ~~directing~~they ~~higher,~~are ~~more~~designed ~~powerful~~to ~~radiation~~deliver ~~doses~~safe atand ~~the~~effective ~~tumor—and~~doses ~~only~~of radiation at the ~~tumor~~tumors—potentially in a single treatment. ByTo ~~minimizing~~achieve ~~radiation~~this, ~~exposure~~we tohave ~~healthy~~developed ~~tissues~~innovative ~~while~~approaches ~~simultaneously~~to ~~maximizing~~drug ~~locoregional~~formulation, ~~delivery~~including ~~and,~~encapsulating ~~thereby,~~radionuclides ~~efficacy,~~such weas ~~hope~~rhenium toisotopes ~~reduce~~with ~~the~~nanoliposomes ~~radiation~~and ~~toxicity~~microspheres. ~~for~~Our ~~patients,~~formulations ~~improving~~are ~~their~~intended ~~quality~~to ofachieve ~~life~~elevated ~~and~~patient-absorbed ~~life~~radiation ~~expectancy.~~doses ~~Our~~and ~~radiotherapeutic~~extend ~~platform,~~retention ~~combined~~times ~~with~~such ~~advances~~that inthe ~~surgery,~~clearance ~~nuclear~~of ~~medicine,~~the ~~interventional~~isotope ~~radiology,~~occurs after significant and essentially complete radiation ~~oncology~~decay, ~~affords~~which uswill ~~the~~contribute ~~opportunity~~and toprovide ~~target~~less anormal ~~broad~~tissue/organ ~~variety~~exposure ofand ~~cancer~~improved ~~types~~safety margins.

~~Our~~By ~~lead~~minimizing ~~radiotherapeutic~~radiation ~~candidate,~~exposure ~~REYOBIQ™~~to ~~(rhenium~~healthy ~~(186Re)~~tissues ~~obisbemeda),~~while issimultaneously ~~designed~~maximizing ~~specifically~~locoregional ~~for~~delivery ~~CNS~~and, ~~cancers including recurrent glioblastoma (“GBM”)~~thereby, ~~leptomeningeal metastases (“LM”)~~efficacy, ~~and~~we ~~pediatric~~hope ~~brain~~to ~~cancers~~reduce ~~(“PBC”)~~the byradiation ~~direct~~toxicity ~~localized~~for ~~delivery~~patients, ~~utilizing~~improving ~~approved~~their ~~standard-~~quality of~~-care~~ ~~tissue~~life ~~access such as with convection-enhanced delivery (“CED”)~~ and ~~intraventricular~~life ~~brain (Ommaya reservoir) catheters~~expectancy. Our ~~acquired~~ radiotherapeutic ~~candidate~~platform, ~~Rhenium-188~~combined ~~NanoLiposome~~with ~~Biodegradable~~advances ~~Alginate~~in ~~Microsphere~~neurosurgery, ~~(“188RNL-BAM”)~~nuclear ismedicine, ~~designed~~interventional toradiology, ~~treat~~neuro-oncology, ~~many~~and ~~solid~~radiation ~~organ~~oncology, ~~cancers~~affords ~~including~~us ~~primary~~the ~~and~~opportunity ~~secondary~~to ~~liver~~target ~~cancers~~a bybroad ~~intra-arterial~~variety ~~injection~~of cancer types.

OnThe ~~April 26, 2024, we acquired all of the right, title and interest in a cerebrospinal fluid cancer diagnostic portfolio known as the “~~CNSide® ~~Platform”~~Cerebrospinal ~~from~~Fluid ~~Biocept,~~Assay ~~Inc. (“Biocept”), which~~ is currently being utilized in the ReSPECT-LM clinical trial funded by the Cancer Prevention and Research Institute of Texas (“CPRIT”). In connection with our business plan for developing the CNSide™ Platform, we formed CNSide Diagnostics, ~~LLC (“CNSide Diagnostics”), a wholly owned subsidiary of the Company,~~ and our board of directors appointed a board of managers for CNSide Diagnostics. We ~~are~~re-introduced ~~planning for~~ the CNSide Cerebrospinal Fluid Tumor Cell Enumeration test (the “CNSide™ Test”), which is a laboratory developed test (“LDT”) in August 2025. The laboratory for the CNSide Test in Houston, toTexas behas ~~re-introduced~~received toa certificate of accreditation from the ~~U.S.~~Centers ~~market~~for ~~starting~~Medicare in& Medicaid Services (“CMS”) which deems the ~~second~~lab ~~quarter~~compliant ofwith ~~2025~~Clinical ~~after~~Laboratory weImprovement ~~complete~~Amendments a(“CLIA”) ~~number~~regulations. ofFurthermore, ~~steps~~CNSide ~~related~~Diagnostics has signed national agreements to ~~certifications,~~provide ~~state~~the ~~licensure,~~CNSide ~~payor~~Test ~~coverages~~with UnitedHealthcare Insurance Company and Humana, ~~reimbursement~~Inc. ~~codes~~effective September 15 and ~~financing~~October 29, 2025, respectively. These agreements expand access to more than 67 million covered lives across the United States.

InOur ~~March~~headquarters ~~2025,~~is welocated ~~moved~~in ~~our headquarters to~~ Houston, Texas, in proximity to world-class cancer institutions and researchers.

Pipeline

Our most advanced investigational drug, ~~REYOBIQ™~~rhenium (186Re) obisbemeda, is a patented radiotherapy potentially useful for patients with CNS and other cancers. WePreclinical ~~announced~~study indata ~~March~~describing ~~2025 that U.S. Food and Drug Administration (“FDA”) conditionally accepted~~ the ~~proprietary~~use ~~name,~~of ~~REYOBIQ™, to be used by us for~~ rhenium (186Re) obisbemeda. ~~Preclinical study data describing the use of REYOBIQ™~~ for several cancer targets have been published in peer-reviewed journals and reported at a variety of medical society peer-reviewed meetings. Besides GBM, LM and PBC, ~~REYOBIQ™~~rhenium (186Re) obisbemeda has been reported to have potential applications for head and neck cancer, ovarian cancer, breast cancer and peritoneal metastases.

The ~~REYOBIQ™~~rhenium (186Re) obisbemeda technology was part of a licensed radiotherapeutic portfolio that we acquired from NanoTx, Corp. (“NanoTx”) on May 7, 2020. The licensed radiotherapeutic has been evaluated in preclinical studies for several cancer targets and we have an active $3.0 million award from U.S. National Institutes of Health/National Cancer Institute which is expected to provide financial support for the continued clinical development of ~~REYOBIQ™~~rhenium (186Re) obisbemeda for recurrent GBM through the completion of a Phase 2 clinical trial, including enrollment of up to 55 patients.

OnPotential ~~August~~Advantages ~~29,~~of ~~2022,~~Rhenium we(186Re) ~~announced~~obisbemeda ~~feedback~~as ~~from~~ a ~~Type~~treatment ~~C meeting with the FDA regarding Chemistry, Manufacturing and Controls practices. The FDA indicated agreement with our proposed application of cGMP guidance~~ for ~~radiotherapeutics,~~Recurrent ~~small~~GBM

~~molecule~~Table ~~drug products and liposome drug products for REYOBIQ™ in support~~ of ongoing and future GBM clinical trials, manufacturing scale up, and commercialization. Alignment with the FDA includes support of our proposed controls and release strategy for new drug substance and new drug product. Because this product is identical for recurrent GBM, LM, and PBC, we believe alignment will be consistent for REYOBIQ™ used in other clinical development programs, including LM and PBC. Contents

~~REYOBIQ™~~Rhenium ~~versus~~(186Re) ~~External~~obisbemeda ~~Beam~~is ~~Radiation~~a ~~Therapy~~novel ~~for~~injectable ~~Recurrent~~radiotherapy designed to deliver targeted, high dose radiation directly into GBM tumors in a safe, effective, and convenient manner that may ultimately prolong patient survival. rhenium (186Re) obisbemeda is composed of the radionuclide Rhenium-186 and a nanoliposomal carrier, and is infused in a highly targeted, controlled fashion, directly into the tumor via precision brain mapping and CED catheters. Potential benefits of rhenium (186Re) obisbemeda compared to standard external beam radiotherapy or external beam radiation therapy (“EBRT”) include:

•

~~REYOBIQ™~~The isrhenium a(186Re) ~~novel~~obisbemeda ~~injectable~~radiation ~~radiotherapy~~dose ~~designed~~delivered to ~~deliver~~patients ~~targeted,~~may ~~high~~be ~~dose~~up ~~radiation~~to ~~directly~~20 ~~into~~times ~~GBM~~greater ~~tumors~~than inwhat ~~a safe, effective, and convenient manner that may ultimately prolong patient survival. REYOBIQ™~~ is ~~composed~~possible ofwith ~~the~~commonly ~~radionuclide~~used ~~Rhenium-186~~EBRT, ~~and~~which, aunlike ~~nanoliposomal~~EBRT ~~carrier,~~ and isproton ~~infused~~beam ~~in a highly targeted~~devices, ~~controlled~~spares ~~fashion,~~normal ~~directly~~tissue ~~into~~and the ~~tumor via precision~~ brain ~~mapping~~from ~~and CED catheters. Potential benefits of REYOBIQ™ compared to standard external beam radiotherapy or external beam~~ radiation ~~therapy (“EBRT”) include:~~exposure.

•

~~The~~Rhenium ~~REYOBIQ™~~(186Re) ~~radiation~~obisbemeda ~~dose~~can ~~delivered to patients may~~ be upvisualized toin 20real-time ~~times~~during ~~greater~~administration, ~~than~~possibly ~~what~~giving isclinicians ~~possible~~better ~~with~~control ~~commonly~~of ~~used~~radiation ~~EBRT~~dosing, ~~which,~~distribution ~~unlike EBRT~~ and ~~proton beam devices, spares normal tissue and the brain from radiation exposure~~retention.

•

~~REYOBIQ™~~Rhenium ~~can~~(186Re) beobisbemeda ~~visualized~~is indesigned ~~real-time~~to ~~during~~effectively ~~administration,~~treat ~~possibly~~a ~~giving~~bulk ~~clinicians~~tumor ~~better~~and ~~control~~microscopic ofdisease ~~radiation~~that ~~dosing,~~has ~~distribution~~already ~~and~~invaded ~~retention~~healthy tissue.

•

~~REYOBIQ™~~Rhenium ~~potentially~~(186Re) ~~more~~obisbemeda ~~effectively~~is ~~treats~~infused adirectly ~~bulk~~into the targeted tumor by CED catheter insertion using MRI guided software to avoid critical patient neurological structures and ~~microscopic~~neural ~~disease~~pathways ~~that~~and ~~has~~also ~~already~~bypasses ~~invaded~~the blood brain barrier, which delivers the therapeutic product where it is needed. Importantly, it reduces radiation exposure to healthy cells, in contrast to EBRT, which passes through normal tissue to reach the tumor, continuing its path through the tumor, hence being less targeted and selective.

•

~~REYOBIQ™~~Rhenium is(186Re) ~~infused~~obisbemeda ~~directly~~is ~~into~~given ~~the~~during ~~targeted~~a ~~tumor~~single, byshort, ~~CED catheter insertion using MRI guided software to avoid critical~~ in-patient ~~neurological~~hospital ~~structures~~visit, and ~~neural pathways and also bypasses the blood brain barrier, which delivers the therapeutic product where it~~ is ~~needed.~~available ~~Importantly,~~in itall ~~reduces~~hospitals ~~radiation~~with ~~exposure~~nuclear tomedicine ~~healthy~~and ~~cells~~neurosurgery, inwhile ~~contrast to~~ EBRT, ~~which~~requires ~~passes~~out-patient ~~through~~visits ~~normal~~five ~~tissue~~days toa ~~reach~~week ~~the~~for ~~tumor,~~approximately ~~continuing~~four ~~its~~to ~~path~~six ~~through the tumor, hence being less targeted and selective~~weeks.

REYOBIQ™ is given during a single, short, in-patient hospital visit, and is available in all hospitals with nuclear medicine and neurosurgery, while EBRT requires out-patient visits five days a week for approximately four to six weeks.

ReSPECT-GBM Trial for Recurrent GBM

GBM affects approximately 15,000 patients annually in the U.S. and is the most common and lethal form of brain cancer. The average life expectancy with GBM is less than 24 months, with a one-year survival rate of 40% and a five-year survival rate of around 5%. There is no clear standard of care for recurrent GBM and the few currently approved treatments provide only marginal survival benefit and are associated with significant side effects, which limit dosing and prolonged use. Approximately 90% of patients experience GBM tumor recurrence at or near the original tumor location, yet there are no FDA-approved treatments in the recurrent or progressive setting that can significantly extend a patient’s life. GBM routinely presents with headaches, seizures, vision changes and other significant neurological complications, with a significant compromise in quality of life. Despite the best available medical treatments, the disease remains incurable. Even after efforts to manage the presenting signs and symptoms and completely resect the initial brain tumor, some microscopic disease almost always remains, and tumor regrowth occurs within months. Complete surgical removal of GBM is usually not possible and GBM is often resistant or quickly develops resistance to most available current and investigational therapies. Today, the treatment of GBM remains a significant challenge and it has been nearly a decade since the FDA approved a new therapy for this disease, and these more recent approvals have not improved the overall survival (“OS”) for GBM patients over past decades, and a significant unmet medical need persists.

While EBRT has been shown to be safe and has temporary efficacy in many malignancies including GBM, typically at absorbed, fractionated radiation dose of ~30 Gray in GBM, this maximum possible administered dose is always limited by toxicity to the normal tissues surrounding the malignancy and because EBRT requires fractionation to manage toxicity, ~~and~~ maximum EBRT limits are typically reached before long-term efficacy is reached. Because of this limitation, EBRT cannot provide a cure or long-term control of GBM and GBM always recurs within months after EBRT. In contrast, locally delivered and targeted radiopharmaceuticals that precisely deliver radiation in the form of beta particles, such as Iodine-131 for thyroid cancer, are known to be safe and effective and minimize exposure to normal cells and tissues especially with optimal administered dose and minimizing exposure to normal tissue. The locally delivered ~~REYOBIQ™~~rhenium (186Re) obisbemeda is designed for and provides patient tolerability and safety. Though no ~~REYOBIQ™~~rhenium (186Re) obisbemeda head-to-head trial with chemo, immune, EBRT or systemic radiopharmaceutical products have been conducted, patient tolerability and safety considerations have been reported as expected.

In ~~September~~ 2020, the FDA granted ~~both~~rhenium (186Re) obisbemeda orphan drug designation for the treatment of GBM and Fast Track ~~designations~~designation ~~to REYOBIQ™~~ for the treatment of ~~patients~~recurrent ~~with~~ GBM.

~~REYOBIQ™~~Rhenium (186Re) obisbemeda is under clinical investigation in a Phase 1/2 multicenter, sequential cohort, open-label, volume and dose escalation study (“ReSPECT-GBM”) of the safety, tolerability, and distribution of ~~REYOBIQ™~~rhenium (186Re) obisbemeda given by CED catheters to patients with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment. The trial is funded through Phase 2 in large part by a National Institute of Health/National Cancer Institute grant.

8We completed Phase 1 of our ReSPECT-GBM Trial and are targeting full enrollment into Phase 2 by the end of 2026.

with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment. The trial is funded through Phase 2 in large part by a National Institute of Health/National Cancer Institute grant.

On January 18, 2023, we announced that the first patient was dosed in Phase 2 of the ReSPECT-GBM Phase 1/2 trial evaluating REYOBIQ™ for the treatment of recurrent GBM. Phase 2 of the trial is expected to enroll up to 34 total patients with small- to medium-sized tumors and is targeted for full enrollment by the end of 2025. We currently have four clinical sites, and expect a data read-out by the end of 2025.

On September 30, 2024, we showcased new interim ReSPECT-GBM Phase 2 Trial Data at the 2024 Congress of Neurological Surgeons Annual Meeting that included the following findings as of that date:

42 total patients enrolled in ReSPECT-GBM trial at 3 sites, with 19 out of 42 patients having been treated at the recommended Phase 2 dose (22.3 mCi in 8.8 mL) in tumors of approximately 20 cm3 or less.

All Phase 2 patients have recurrent, histologically confirmed glioblastoma; 1 recurrence, bevacizumab naïve, single tumor of approximately 20 cm3 or less (small-to-medium sized tumors).

Average tumor size in Phase 2 was 7.5 mL (range 0.9-22.8 mL).

Increases in absorbed dose correlated with specific drug delivery parameters such as infused dose and volume, maximal convection flow rate, and number of catheters.

REYOBIQ™ continues to show a favorable safety profile in the 42 enrolled patients; one dose-limiting toxicity (hemiplegia) has been reported, which was observed in Cohort 8 (41.5 mCi and 16.3 mL).

In Phase 2, most adverse events were mild (73.5%) or moderate (18.8%), and largely unrelated (37.7%), or unlikely related (27.1%) to the drug. Of the 9 severe adverse events, only 2 were related to the study drug.

Average absorbed radiation dose to the tumor in Phase 2 was 300 Gy (n=18, 1 patient still under analysis).

88.9% of Phase 2 patients met key CED drug delivery parameters shown to correlate with overall survival, achieving a tumor absorbed dose >100 Gy and radiation coverage of >70%.

29 out of 42 patients treated thus far participated in the Phase 1 dose escalation phase of the trial (as per protocol, 6 out of 42 patients were included in both the Phase 1 and Phase 2 trial arms and related analyses).

Phase 1 dose-escalation increased administered doses from 1.0 mCi to 41.5 mCi and volumes from 0.66 mL to 16.3 mL.

In terms of objective tumor response based on quantitative image analysis, a statistically significant reduction in tumor volume rate change was seen in tumors receiving > 100 Gy absorbed dose (n=11 patients analyzed to date, p<0.005). Sufficient tumor coverage correlated with tumor control, while regrowth occurred outside treated areas.

We completed Phase 1 of our ReSPECT-GBM Trial and are targeting full enrollment into Phase 2 by the end of 2025.

ReSPECT-LM Clinical Trials for LM

Table of Contents

LM is a rare complication of cancer in which the disease spreads to the membranes (meninges) surrounding the brain and spinal cord. The incidence of LM is growing and occurs in approximately 5%, or more, of people with late-stage cancer, or 110,000 people in the U.S. each year. It is highly lethal with an average one-year survival of just 7%. All solid cancers, particularly breast, lung, GI, and melanoma, have the potential to spread to the leptomeninges.

The ReSPECT-LM Phase 1 clinical trial (ClinicalTrials.gov NCT05034497) was preceded ~~with~~by preclinical studies in which tolerance to doses of ~~REYOBIQ™~~rhenium (186Re) obisbemeda as high as 1,075 Gy were shown in animal models with LM without significant observed toxicity. Furthermore, treatment led to a marked reduction in tumor burden in both C6 and MDA-231 LM models.

Upon receiving acceptance of our Investigational New Drug application and Fast Track designation by the FDA for ~~REYOBIQ™~~rhenium (186Re) obisbemeda for the treatment of LM in November 2021, we initiated the trial and began screening patients for the ReSPECT-LM Phase 1 clinical trial in the fourth quarter of 2021.

ReSPECT-LM is a multi-center, sequential cohort, open-label, dose escalation study evaluating the safety, tolerability, and efficacy of a single-dose application of ~~REYOBIQ™~~rhenium (186Re) obisbemeda administered through intrathecal infusion to the ventricle of patients with LM after standard surgical, radiation, and/or chemotherapy treatment. The primary endpoint of the study is the incidence and severity of adverse events and dose limiting toxicities, together with determining the maximum tolerated and recommended Phase 2 dose. Full enrollment in the Phase 1 trial was achieved at the end of 2024, and we announced the trial completion on February 26, 2025. Trial closeout procedures are now taking place including final data review and monitoring, and a clinical study report and manuscript will be prepared.

On September 19, 2022, we entered into a Cancer Research Grant Contract (the “CPRIT Contract”), effective as of August 31, 2022, with CPRIT, pursuant to which CPRIT provides us a grant of up to $17.6 million (the “CPRIT Grant”) over a three-year period to fund the continued development of rhenium (186Re) obisbemeda for the treatment of patients with LM through Phase 2 of the ReSPECT LM clinical trial. The CPRIT Grant is subject to customary CPRIT funding conditions, including, but not limited to, a matching fund requirement (one dollar from us for every two dollars awarded by CPRIT), revenue sharing obligations upon commercialization of rhenium (186Re) obisbemeda based on specific dollar thresholds until CPRIT receives the aggregate amount of 400% of the proceeds awarded under the CPRIT Grant, and certain reporting requirements. As of December 31, 2025, we had received approximately $15.9 million in milestone payments under the CPRIT Contract.

OnInterim ~~September~~results ~~19,~~showed ~~2022,~~that ~~we entered into~~ a ~~Cancer~~single ~~Research~~treatment ~~Grant~~with ~~Contract~~rhenium (~~the “CPRIT Contract”~~186Re), ~~effective~~obisbemeda asresulted ofin ~~August 31, 2022, with CPRIT, pursuant to which CPRIT provides us~~ a ~~grant~~consistent ofdecreased upcerebrospinal tofluid ~~$17.6 million~~ (~~the~~ “~~CPRIT Grant~~CSF”) ~~over~~circulating atumor ~~three-year~~cell ~~period~~(“CTC”) tocount/ml ~~fund~~and ~~the~~was ~~continued~~tolerated ~~development~~by ofall ~~REYOBIQ™ for the treatment of patients with~~ LM ~~through Phase 2 of the ReSPECT LM clinical trial~~patients. ~~The~~Rhenium ~~CPRIT~~(186Re) ~~Grant~~obisbemeda is ~~subject~~an tooutpatient ~~customary~~administration ~~CPRIT~~and ~~funding~~treatment ~~conditions,~~and ~~including,~~is ~~but~~easily ~~not~~and ~~limited~~safely ~~to,~~administered through a ~~matching~~standard ~~fund~~intraventricular ~~requirement~~catheter (~~one~~Ommaya ~~dollar from us for every two dollars awarded by CPRIT~~Reservoir), ~~revenue~~distributed ~~sharing~~promptly ~~obligations~~throughout ~~upon commercialization of REYOBIQ™ based on specific dollar thresholds until CPRIT receives~~ the ~~aggregate~~CSF, ~~amount~~and ofwith ~~400%~~durable ofretention ~~the~~in ~~proceeds awarded under~~ the ~~CPRIT~~leptomeninges ~~Grant,~~at ~~and~~least ~~certain~~through ~~reporting~~day ~~requirements~~seven. AsAll ofpatients ~~December~~have ~~31,~~shown ~~2024,~~well wetolerated ~~had~~prompt ~~received~~and ~~approximately~~durable ~~$10.4~~rhenium ~~million~~(186Re) inobisbemeda ~~milestone~~distribution ~~payments~~throughout ~~under~~ the ~~CPRIT~~subarachnoid ~~Contract~~space.

~~Interim~~In ~~results~~November ~~showed~~2023, ~~that~~the aFDA ~~single~~granted ~~treatment~~orphan ~~with~~drug ~~REYOBIQ™~~designation ~~resulted~~to inrhenium ~~a consistent decreased cerebrospinal fluid~~ (~~“CSF”~~186Re) ~~tumor~~obisbemeda ~~cell~~for ~~count/ml~~the ~~and~~treatment ~~was~~of ~~tolerated by all LM~~ patients. ~~REYOBIQ™~~with isbreast ancancer ~~outpatient administration and treatment and is easily and safely administered through a standard intraventricular catheter (Ommaya Reservoir), distributed promptly throughout the CSF, and~~ with ~~durable retention in the leptomeninges at least through day seven~~LM. ~~All patients have shown well tolerated prompt and durable REYOBIQ™ distribution throughout the subarachnoid space.~~

InOn ~~November~~December 12, 2023, ~~the~~we ~~FDA~~announced ~~granted~~our ~~orphan~~partnership ~~drug~~with ~~designation~~K2bio to ~~REYOBIQ™~~implement ~~for~~ the ~~treatment~~CNSide ~~of patients with breast cancer with LM~~Test.

On December 12, 2023, we announced our partnership with K2bio to implement novel analysis for CSF tumor and molecular biomarkers for CNS cancers.

On February 26, 2025, we announced the completion of the ReSPECT-LM Phase 1 single-dose escalation trial, having determined a recommended Phase 2 dose. Enrollment in Cohort 6 was completed (75.0 mCi). The Cohort 4 dose (44.1 mCi) was determined to be the recommended Phase 2 dose with no dose-limiting toxicities observed at that dose level. One patient at the Cohort 4 dose was observed to have achieved a complete response, as evidenced by the eradication of tumor cells in the cerebrospinal fluid—a key therapeutic endpoint.

~~We anticipate beginning enrollment for a ReSPECT-LM Multi-Dose trial in the first half of 2025.~~ In March 2025, the FDA granted orphan drug designation to ~~REYOBIQ™~~rhenium (186Re) obisbemeda for the treatment of LM in patients with lung cancer.

In November 2025, we had our end of phase 1 meeting with the FDA. During this meeting, FDA conveyed that while accelerated approval may be appropriate for this indication, there are insufficient data to support the use of CTCs as an intermediate clinical endpoint, and there was discussion that additional steps would be necessary to validate CTCs as a surrogate endpoint to potentially support other future applications. The FDA recommended that the study evaluate an endpoint with established clinical benefit, such as overall survival, while encouraging further study of reported outcomes and neurologic function as endpoints that could potentially support a marketing application. We agreed with FDA that CTCs could be considered for use as a secondary endpoint. We discussed with the FDA a randomized controlled trial design approach and that the study may include an itrathecal chemotherapeutic as a comparator, as well as approaches to standardize the comparator and any additional interventions available under the trial protocol. The FDA conveyed it may be reasonable to incorporate multiple histologies (i.e., multiple underlying disease etiologies) in a single trial. We plan to consider the Agency’s feedback and propose an updated protocol for our next study for FDA’s feedback.

In December 2025, we reported completion of the ReSPECT-LM single dose trial showed rhenium (186Re) obisbemeda was well-tolerated up to a maximum tolerated dose of 66mCi, with a recommended phase 2 dose of 44.1 mCi, and absorbed doses delivered of >300 Gy observed. We also reported the ReSPECT-LM open label, multidose Phase 1/2 trial initiation to identify maximum tolerated dose across varying dosing intervals and to characterize efficacy of multiple doses at optimal dose selected by assessing response using the CNSide Test. Enrollment in Cohort 1 has begun with delivery of 13.2 mCi at 3 intervals with one patient receiving all doses without dose limiting toxicity.

Table of Contents

Our ReSPECT LM Multi-dose Phase 1/2 Study is currently enrolling patients for the Phase 2 portion of the Study.

ReSPECT-PBC Clinical Trial for Pediatric Brain Cancer

The average annual age adjusted mortality rate for children aged 0-14 for malignant brain (and other CNS) tumors is 0.71/100,000, making it the most common cause of death and cancer death in this age group. The 2021 World Health Organization Classification of CNS Tumors classifies gliomas, glioneuronal tumors, and neuronal tumors into six different families: (1) adult-type diffuse gliomas; (2) pediatric-type diffuse low-grade gliomas; (3) pediatric-type diffuse high-grade gliomas (“HGG”); (4) circumscribed astrocytic gliomas; (5) glioneuronal and neuronal tumors; and (6) ependymomas.

In August 2021, we announced plans for treating pediatric brain cancer at the 2021 American Association of Neurological Surgeons Annual Scientific Meeting. In July 2021, we reported that we had received FDA feedback pertaining to a pre-~~Investigational New Drug Application (“~~IND”) meeting briefing package in which the FDA stated that we are not required to perform any additional preclinical or toxicology studies. A new IND submission was made in 2023.

Given the initial FDA feedback, receipt of adult GBM data and experience with REYOBIQ™ and follow-up communications with the FDA, we submitted a pediatric brain tumor IND for our ReSPECT-PBC clinical trial to investigate the use of REYOBIQ™ in two pediatric brain cancers, high-grade glioma and ependymoma, in the fourth quarter of 2024.

Pediatric high-grade gliomas can be found almost anywhere within the CNS; however, they are most commonly found within the supratentorium. The highest incidence of supratentorial, high-grade gliomas in pediatrics appears to occur in children aged 15 to 19 years, with a median age of approximately nine years. Overall, pediatric high-grade glioma confers a three-year progression free survival (“PFS”) of 11 ± 3% and three-year OS of 22 ±5%. One-year PFS is as low as 40% in recent trials. Ependymomas are slow-growing central nervous system tumors that involve the ventricular system. Diagnosis is based on MRI and biopsy and survival rate depends on tumor grade and how much of the tumor can be removed. Grade II pathology was associated with significantly improved OS compared to Grade III (anaplastic) pathology (five-year OS = 71 ± 5% vs. 57 ± 10%; p = 0.026). Gross total resection compared to subtotal resection was associated with significantly improved OS (five-year OS = 75 ± 5% vs. 54 ± 8%; p = 0.002).

Overall, pediatric HGG and ependymoma are extremely difficult-to-treat pediatric brain tumors, frequently aggressive, and in recurrent settings, carry an extremely poor prognosis.

Effective September 1, 2024, we entered into an agreement with the Department of Defense office of the Congressionally Directed Medical Research Programs to receive a $3.0 million fund for research and development purposes (“DoD Award”) over a three-year period. The DoD Award will be used to support the planned expansion of our clinical trial for pediatric brain cancer. We anticipate ~~beginning~~enrolling ~~enrollment~~our first patient for our Phase 1 ReSPECT-PBC clinical trial in ~~the first half of 2025~~2026.

10On June 25, 2025, we announced that the FDA cleared our IND application (No. 168178) for rhenium (186Re) obisbemeda for the treatment of pediatric patients with supratentorial recurrent, refractory, or progressive high-grade glioma (“HGG”) and ependymoma. The Phase 1/2a trial is a two-part, single-arm, prospective study aimed at determining the maximum tolerated dose (“MTD”), safety, and tolerability of rhenium (186Re) obisbemeda in pediatric patients aged 6 to 21 years (with consideration for patients up to 25 years on a case-by-case basis).

Key elements of the trial design include:

•

Phase 1a/b (dose escalation): This phase will enroll an estimated 24 patients using a modified 3+3 dose escalation scheme to establish the MTD and recommended Phase 2 dose (“RP2D”). Safety assessment and alignment with the FDA will occur at defined intervals.

•

Phase 2a: This phase will enroll approximately 32 patients (12 with ependymoma and 20 with HGG) at the RP2D to assess efficacy.

•

We anticipate beginning enrollment in our ReSPECT-PBC clinical trial, with our first patient enrolled, in 2026.

Rhenium-188 NanoLiposome Biodegradable Alginate Microsphere Technology

In January 2022, we announced that we licensed Biodegradable Alginate Microsphere (“BAM”) patents and technology from The University of Texas Health Science Center at San Antonio (“UTHSCSA”) to expand our tumor targeting capabilities and precision radiotherapeutics pipeline. We intend to combine our Rhenium NanoLiposome technology with the BAM technology to create a novel radioembolization technology. Initially, we intend to utilize the Rhenium-188 isotope, 188RNL-BAM for the intra-arterial embolization and local delivery of a high dose of targeted radiation for a variety of solid organ cancers such as hepatocellular cancer, hepatic metastases, pancreatic cancer and many others.

Preclinical data from an ex vivo embolization experiment in which Technetium99m-BAM was intra-arterially delivered to a bovine kidney perfusion model was presented at the Society of Interventional Radiology Annual Scientific Meeting. The study concluded that the technology required for radiolabeling BAM could successfully deliver, embolize and retain radiation in the target organ. 188RNL-BAM is a preclinical investigational device we intend to further develop and move into clinical trials. Specifically, in 2022 we transferred the 188RNL-BAM technology from UTHSCSA, and began planning to develop the product and complete early preclinical studies to support a future FDA IND submission. Our intended initial clinical target is liver cancer which is the sixth most common and third deadliest cancer worldwide. It is a rare disease with increasing U.S. annual incidence (42,000) and deaths (30,000).

~~The~~8 ~~FDA has informed us that 188RNL-BAM will be regulated as a medical device under the Federal Food, Drug, and Cosmetic Act (the “FDCA”).~~

~~The~~Table ~~CNSideTM~~of ~~FORESEE Trial~~ Contents

~~The~~FDA ~~CNSide™~~IND ~~Platform consists of four LDTs used for treatment selection and treatment monitoring of patients with LM~~submission. ~~The~~Our ~~CNSide™~~intended ~~Platform~~initial ~~facilitates~~clinical ~~tumor~~target ~~cell~~is ~~detection/enumeration~~liver ~~and~~cancer ~~biomarker~~which ~~identification~~is ~~using~~the ~~cellular~~sixth ~~assays~~most ~~(immunocytochemistry~~common ~~(ICC)~~ and ~~fluorescence~~third indeadliest ~~situ~~cancer ~~hybridization (FISH)) and molecular assays (next-generation sequencing (NGS))~~worldwide. ~~The~~It ~~CNSide™ Test~~ is ~~currently~~a ~~being~~rare ~~used~~disease inwith ~~the~~increasing ~~ReSPECT-LM trial as an exploratory endpoint and we are planning to re-introduce it to the~~ U.S. ~~market~~annual ~~starting~~incidence in(42,000) ~~the~~and ~~second~~deaths ~~quarter of 2025~~(30,000).

~~In August 2024~~Subsequently, ~~data from~~ the ~~CNSideTM FORESEE~~FDA ~~clinical~~has ~~trial~~informed inus ~~patients~~that ~~with~~188RNL-BAM LMwill ~~was~~be ~~presented~~regulated atas ~~the~~a ~~Society~~medical ~~for~~device ~~Neuro-Oncology~~under ~~(“SNO”)~~the /Federal ~~American~~Food, ~~Society~~Drug, ~~for~~and ~~Clinical~~Cometic ~~Oncology~~Act (“~~ASCO~~FDCA”) ~~CNS Metastases Conference~~. The trial met its key primary and secondary endpoints and the data showed that the CNSideTM Test more than doubled the diagnostic sensitivity versus gold standard cerebrospinal fluid cytology and influenced clinical management decisions in over 90% of LM cases.

OnThe ~~November 24, 2024,~~ CNSide ~~Diagnostics~~CSF ~~presented~~Assay ~~data at the 2024 SNO Annual Meeting from the FORESEE trial showcasing the CNSideTM~~ Platform~~’s utility in diagnosing and guiding clinical decision making for breast cancer and non-small cell lung cancer patients with LM.~~

~~Key~~The ~~highlights~~CNSide ~~included:~~CSF Assay Platform consists of four LDTs used for detection, quantification, and characterization of tumor cells in patients with LM. The CNSide Platform facilitates tumor cell detection/enumeration and biomarker identification using cellular assays (tumor cell enumeration (“TCE”), immunocytochemistry (“ICC”), and fluorescence in situ hybridization (“FISH”)) and molecular assays (next-generation sequencing (“NGS”)). The CNSide Test is currently being used in the ReSPECT-LM trial as an exploratory endpoint.

~~The~~Since ~~FORESEE~~acquiring ~~trial~~the ~~achieved~~CNSide ~~its~~Platform ~~primary~~in ~~endpoint~~2024, ~~demonstrating~~we have established infrastructure to support a scalable and centralized testing laboratory in Houston, TX that will service the ~~CNSideTM~~U.S. ~~Test~~market. ~~influenced~~We ~~treatment~~have ~~decisions~~been executing on our commercial market access strategy, which includes prioritized state licensure, proprietary reimbursement codes, commercial and government payor coverage, and value-based pricing to optimize revenue. We re-introduced the CNSide Platform first in ~~over~~Texas ~~90%~~in August of ~~cases~~2025, ~~evaluated~~signed a national agreement to provide the CNSide Test with UnitedHealthcare Insurance Company and Humana, ~~surpassing~~Inc., and obtained state licensure for 49 of 50 US states by January 2026, with the ~~predetermined~~remaining ~~20%~~license ~~primary~~for ~~endpoint~~the ~~target~~state of New York on track for 2027. In parallel, we expect to launch a portfolio of additional CSF tumor characterization tests that expand our CNSide testing platform later in 2026.

~~The~~When ~~CNSideTM~~the ~~Test~~CNSide ~~demonstrated~~CSF ~~enhanced~~Assay ~~sensitivity~~Platform was previously commercially available, market acceptance and adoption were widespread, with several national and regional commercial payor agreements in ~~detecting~~place ~~tumor~~and ~~cells~~the ~~(80%)~~test vsin regular use at major cancer centers across the U.S. ~~CSF~~We ~~cytology~~are ~~(29%)~~now in ~~patients~~contact with LMthe legacy payors and healthcare providers to support our commercial scale up in 2026. Finally, we have hired experienced leadership with expertise in the development and commercialization of clinical diagnostic technologies on a large scale.

The CNSideTM Test identified actionable mutations in the CSF, such as HER2 amplification, influencing 24% of therapeutic selection decisions.

The CNSideTM Test exhibited high specificity, with no tumor cells detected in patients without LM.

The CNSideTM Test demonstrated improved Negative Predictive Value in ruling out LM (25%) vs. CSF cytology (10%).

The CNSideTM Test revealed HER2 positivity in LM tumors in 60% of breast cancer patients with HER2-negative primary tumors, informing physician treatment strategies.

Licensing

On December 31, 2021, we entered into a Patent and Technology License Agreement (the “UTHSCSA License Agreement”) with UTHSCSA, pursuant to which UTHSCSA granted us an irrevocable, perpetual, exclusive, fully paid-up license, with the right to sublicense and to make, develop, commercialize and otherwise exploit certain patents, know-how and technology related to the development of BAM containing nanoliposomes loaded with imaging and/or therapeutic payloads. Therapeutic payloads may include radiotherapeutics, chemotherapeutics, or thermotherapeutics.

The BAM technology is delivered directly into the intra-arterial vascular system via commonly utilized and standard interventional vascular catheters and techniques that allow precise placement into the arterial blood vessels feeding tumors. Once injected, the BAM technology provides a potential dual therapeutic delivery—blocking blood flow to the tumors by alginate microsphere tumor capillary embolization with simultaneous delivery of very high doses of cytotoxic compounds including radiation, such as nanoliposome encapsulated bi-functionally chelated Re-188, for an extended time. Weeks later, the delivered BAM are physiologically metabolized allowing excretion from the body. Rhenium-188 is an attractive and ideal therapeutic isotope for this application because of its 16.9 hour half-life, 2.12MEV β-decay and ~3.8mm tissue path-length, and simultaneous 155Kev γ-decay that allow simultaneous SPECT/CT imaging with commonly available imaging equipment to easily and non-invasively monitor product administration, delivery and dosimetry absorbed dose evaluation.

injected, the BAM technology provides a potential dual therapeutic delivery—blocking blood flow to the tumors by alginate microsphere tumor capillary embolization with simultaneous delivery of very high doses of cytotoxic compounds including radiation, such as nanoliposome encapsulated bi-functionally chelated Re-188, for an extended time. Weeks later, the delivered BAM are physiologically metabolized allowing excretion from the body. Rhenium-188 is an attractive and ideal therapeutic isotope for this application because of its 16.9 hour half-life, 2.12MEV β-decay and ~3.8mm tissue path-length, and simultaneous 155Kev γ-decay that allow simultaneous SPECT/CT imaging with commonly available imaging equipment to easily and non-invasively monitor product administration, delivery and dosimetry absorbed dose evaluation.

We currently anticipate that we will initially focus on developing 188RNL-BAM as a next-generation radioembolization therapy for liver cancer, in which BAM blocks the hepatic artery segments that supply blood to the malignant tumor while also providing 188RNL radiotherapy directly to the tumor and surrounding tissue. According to the American Cancer Society, liver cancer is a rare disease with an increasing annual incidence and five-year overall survival of only 20%.

The financial terms of the UTHSCSA License Agreement are primarily success-based with milestone and royalty payments contingent on achieving key clinical, regulatory and sales milestones.

The initial inventions and work behind the licensed patents and technologies were developed and led by William Phillips MD, Professor of Nuclear Medicine, and his team at UTHSCSA. The 188RNL-BAM technology incorporates Rhenium-188, or 188Re, a unique isotope for radiotherapeutic embolization owing to its emission of a high energy (2.12Mev) electron (beta particle, 16.9-hour half-life with a 3.8mm decay path length). 188Re also emits 155kev gamma energy that permits high quality, real-time imaging of the BAM construct delivery localization and confirmation. BAMs are not permanent and are anticipated to degrade over time, allowing restoration of blood flow, decreasing radiation resistance, and allowing for safer physiological clearance of 188Re through the kidneys, which may minimize bone marrow toxicity.

The transaction terms include an upfront payment in cash. We are also required to pay development and sales milestone payments, if achieved, and a tiered single-digit royalty on U.S. and European sales. In addition, we may be obligated to pay an annual maintenance fee beginning in 2024.

On March 29, 2020, we entered into a Patent and Know-How License Agreement (the “NanoTx License Agreement”) with NanoTx, pursuant to which NanoTx granted us an irrevocable, perpetual, exclusive, fully paid-up license, with the right to sublicense and to make, ~~develop, commercialize and otherwise exploit certain patents, know-how and technology related to the development of radiolabeled nanoliposomes.~~

Table of Contents

develop, commercialize and otherwise exploit certain patents, know-how and technology related to the development of radiolabeled nanoliposomes.

The transaction terms included an upfront payment of $0.4 million in cash and $0.3 million in our voting stock. The transaction terms also included success-based milestone and royalty payments contingent on key clinical, regulatory and sales milestones, as well as the requirement to pay 15% of any non-dilutive monetary awards or grants received from external agencies to support product development of the nanoliposome encapsulated BMEDA-chelated radioisotope, which includes grants from CPRIT.

The licensed NanoTx portfolio benefits from proprietary nanoliposome-encapsulated technology to encapsulate radionuclides allowing direct local delivery for several cancer targets.

The licensed radiolabeled nanoliposome platform was developed by a multi-institutional consortium based in Texas at the Mays Cancer Center / UTHSCSA MD Anderson Cancer Center led by Dr. Andrew Brenner, MD, PhD, who is the Kolitz Chair in Neuro-Oncology Research and Co-Leader of the Experimental and Developmental Therapeutics Program. The technology was previously owned by NanoTx and funded by both the NIH/NCI and CPRIT. There is an active $3 million award from NIH/NCI that is expected to financially support the continued clinical development of ~~REYOBIQ™~~rhenium (186Re) obisbemeda for recurrent GBM.

Manufacturing

WeFor rhenium (186Re) obisbemeda, we have entered into master services agreements with third parties, including Piramal Pharma Solutions, Inc., ABX Advanced Biochemical Compounds GmbH, Telix IsoTherapeutics Group, LLC, Radiomedix, Inc., Alamo Nuclear Pharmacy Services, Inc., and Nuke Med, Inc. (aka SpectronRx) in connection with the development, manufacture, and supply of our ~~REYOBIQ™~~rhenium (186Re) obisbemeda drug product. Upon completion of the research and development phase of a drug candidate, certain parts of the manufacturing processes for such candidate may be transferred to contract manufacturers to support clinical trials and commercial release. Upon approval of our drug candidates, we expect our manufacturing capabilities to include validated manufacturing processes for the drug product as well as a quality assurance product release process with the ability to ultimately scale-up the process to meet increasing market demands. We believe our strategic investments in our analytical, development and manufacturing capabilities, including personnel with expertise from drug discovery through drug development, will allow us to advance our product candidates more quickly. Expertise gained in manufacturing our drug products may be applied to other formulations in the future, further leveraging our capabilities.

12With respect to CNSide, dedicated manufacturing operations for the CNSide platform have been established, including production of proprietary microfluidic chips and associated reagents. Automation of key production steps, together with defined process and quality controls, has improved efficiency and strengthened manufacturing reliability. These advancements have transitioned CNSide manufacturing from development-stage workflows into a scalable production platform.

The design and planned build-out of the Levit Green facility are advancing, with the objective of increasing production capacity and further standardizing operations. In parallel, ERP infrastructure is being implemented to enhance inventory visibility and production planning in support of anticipated manufacturing growth.

Competition

Our business is conducted in intensely competitive and highly regulated markets. The life science industry is characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary therapeutics. We face competition from a number of sources, some of which may target the same indications as our products, product candidates and laboratory tests, including small and large, domestic and multinational, medical device, biotechnology and pharmaceutical companies, academic institutions, government agencies, private and public research institutions and clinical laboratories. Competitors may have greater experience in, and resources to devote to, developing drugs and clinical laboratory tests, conducting clinical trials, obtaining regulatory clearances or approvals, manufacturing and commercialization.

We expect that product candidates in our pipeline, if approved, would compete on the basis of, among other things, product efficacy and safety; time to market; price, coverage, and reimbursement by third-party payers; extent of adverse side effects; and convenience of treatment procedures.

Competition for our product candidate, particularly ~~REYOBIQ™~~rhenium (186Re) obisbemeda and 188RNL-BAM may come from a single or combination therapy in the future.

Currently, there are many other entities pursuing drug development programs for the indications we are currently pursuing with our product candidates.

Significant competitors that have reported drug development programs or clinical laboratory tests at various clinical stages for the various indications listed include, but are not limited to:

Recurrent Glioblastoma

~~EnGeneIC,~~10 Berg, Istari, AstraZeneca, Novartis, PharmAbcine, Kairos, Midatech, Oncovir, Infuseon, Astellas, NanoPharmaceuticals, Erasca, OX2, Crimson BioPharm, TMUNITY, Pfizer, Arcus, Photolitec, Samus, DNAtrix, ImmVira, BerGenBio, Boston Scientific, BeiGene, GSK, Bristol Myers Squibb, Eli Lilly, Sumitomo, QED, Chimerix, Accenda, Oblato, VBI, INIGHTEC, Sonalasense, VBL, Medicenna, Mimiva, Carthera, Gilead, CNS Pharmaceuticals, VAXIMM, Incyte, Celularity, Medicinova, Karyopharm, Nerviano Medical Sciences, Merck, Telix, Neonc, Nuvation Bio, Aadi, ERC, Kazia, Xoft, Basilea, Vigo, Biohaven, Bayer, Kintara, and others have reported drug development programs at various clinical stages for recurrent GBM.

Table of Contents

EnGeneIC, Berg, Istari, AstraZeneca, Novartis, PharmAbcine, Kairos, Midatech, Oncovir, Infuseon, Astellas, NanoPharmaceuticals, Erasca, OX2, Crimson BioPharm, TMUNITY, Pfizer, Arcus, Photolitec, Samus, DNAtrix, ImmVira, BerGenBio, Boston Scientific, BeiGene, GSK, Bristol Myers Squibb, Eli Lilly, Sumitomo, QED, Chimerix, Accenda, Oblato, VBI, INIGHTEC, Sonalasense, VBL, Medicenna, Mimiva, Gilead, CNS Pharmaceuticals, VAXIMM, Incyte, Celularity, Medicinova, Karyopharm, Nerviano Medical Sciences, Merck, Telix, Neonc, Nuvation Bio, Aadi, ERC, Kazia, Xoft, Basilea, Vigo, Biohaven, Bayer, Kintara, CarThera, Everfront Biotech, and others have reported drug development programs at various clinical stages for recurrent GBM.

Leptomeningeal Metastases

~~Angiochem, Y-mAbs, Roche, Bristol Myers Squibb, Merck,~~ Kazia, AstraZeneca, Pfizer, ~~Memorial~~Daiichi-Sankyo, ~~Sloan Kettering~~Genentech, ~~University of Virginia~~Janssen, ~~Wake~~NRG ~~Forest University~~Oncology, ~~University of Alabama Birmingham~~Angiochem, and others have reported drug development programs at various clinical stages for LM.

Pediatric Brain Cancer

AstraZeneca, Bristol Myers Squibb, Chimerix, Celgene, Eli Lilly, Nektar Therapeutics, Istari Oncology, Novartis, NovoCure, Takeda, Y-mAbs, Cellectar, and others have reported drug development programs at various clinical stages for PBC.

Liver Cancer

Boston Scientific, SIR-TEX, ~~Terumo,~~ ABK Biomedical, and others have reported radioembolization therapy product development programs for liver cancer.

~~CNSideTM~~CNSide Test

Menarini, Belay Diagnostics, BillionToOne, FYR Diagnostics, Cerevention, Genomic Testing Cooperative, Predicine, Neogenomics, Quest, and LabCorp are current or potential future competitors of our ~~CNSideTM~~CNSide Test.

Intellectual Property

Our success depends in large part on our ability to protect our proprietary technology, and to operate without infringing on the proprietary rights of third parties. We rely on a combination of patent, trade secret, copyright and trademark laws, as well as confidentiality agreements, licensing agreements and other agreements, to establish and protect our proprietary rights. Our success also depends, in part, on our ability to avoid infringing patents issued to others.

We license the proprietary formulation and proprietary methods of manufacture of the nanoliposome-encapsulated radionucleotides. ~~REYOBIQ™~~rhenium (186Re) obisbemeda, 188RNL-BAM, and their method of manufacture are covered by a U.S. patent that will expire in December 2026. Patent term extension, codified in 35 U.S.C. §156, provides a means of recapturing time lost during the regulatory approval process. Based upon this regulation, we will apply for patent term extension for this patent for the time lost to development and regulatory review for rhenium (186Re) obisbemeda. This has the potential to extend patent coverage for this product for up to another five years.

December 2026. Patent term extension, codified in 35 U.S.C. §156, provides a means of recapturing time lost during the regulatory approval process. Based upon this regulation, we will apply for patent term extension for this patent for the time equal to the regulatory review period for REYOBIQ™. This has the potential to extend patent coverage for this product for up to another five years.

188RNL-BAM is also covered by a licensed patent family directed to a method of producing liposome-containing alginate microspheres. Any patent granted from applications claiming priority to it is expected to expire in May 2040, not including any patent term adjustment or patent term extension and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The patent family includes issued patents in Japan, Singapore, Canada, and Mexico, in addition to pending applications in the United States, Canada, Israel, India, Mexico, Saudi Arabia, Thailand, South Africa, Vietnam, Philippines, China, Europe, Brazil, Singapore, Indonesia, Malaysia, Hong Kong, Australia, and New Zealand.

188RNL-BAM is also covered by a licensed patent family directed to a method for post-manufacture loading of a liposome-containing hydrogel microsphere. Patent granted from applications in this family are expected to expire in March 2042, not including any patent term adjustment or patent term extension and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The patent family includes applications pending in the United States, Australia, Canada, Brazil, South Korea, China, Europe, Mexico, and Israel.

We co-own a patent family directed to methods of treating a disease, including, but not limited to cancer, comprising administering 186Re and 188Re nanoliposomes via CED. Any patents issued from applications in this family are expected to expire in November 2041, not including any patent term adjustment or patent term extension and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The patent family includes applications pending in the U.S., Australia, Brazil, Canada, China, Europe, Indonesia, Israel, Japan, South Korea, Malaysia, Hong Kong, and Mexico.

We co-own a patent family directed to methods of treating leptomeningeal metastases comprising administering 186Re and/or 188Re nanoliposomes via an intraventricular reservoir. Any patent granted from applications in this family are expected to expire in January 2043, not including any patent term adjustment or patent term extension and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The patent family includes applications pending in the U.S., Australia, Brazil, Canada, China, Europe, Indonesia, Israel, Japan, South Korea, Malaysia, and Mexico.

Table of Contents

We own a patent family directed to a method of manufacturing a polymeric matrix encapsulating microsomes. Any patent granted from applications in this family is expected to expire in December 2043, not including any patent term adjustment or patent term extension and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. Applications are pending in the PCT and U.S. The 30-month deadline to file national stage applications claiming priority to the PCT application is June 2025.

We have broad patent protection related to the ~~CNSideTM~~CNSide Platform, including our ownership of the following patents, patent families and applications:

•

A U.S. patent directed to beads for capturing target cells from a bodily fluid. This patent will expire in December 2025 assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

A patent family directed to a microflow device for separating or isolating cells from a bodily fluid or other liquid sample. There are patents in the U.S., China, Europe (validated in France, Germany, Italy, Spain, and the United Kingdom), Hong Kong, China, and Japan. There is an application pending in the U.S. The patents will expire in 2026 assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

•

A patent family directed to a microflow device for separating or isolating cells from a bodily fluid or other liquid sample. There are patents in the U.S., Canada, China, and Hong Kong. The patents will expire in 2026 and 2027 assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

•

A patent family directed to a device and methods for isolating target biomolecules or cells from samples. There are patents in the U.S., Australia, Europe (validated in the United Kingdom, France, Spain, Germany, Switzerland, and Italy), China, Japan, Canada, and Hong Kong. There is an application pending in the U.S. The patents will expire in 2030 and 2031 assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

•

A patent family directed to reagents containing binding moieties conjugated to dextran moieties, methods of making such reagents, and use of such reagents in a variety of molecular and cellular assays. There are patents in the U.S., Japan, China, Canada, Europe (validated in France, Germany, Italy, Switzerland, and the United Kingdom), and Hong Kong. The patents will expire in 2031 assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

•

A U.S. patent directed to a microarray for assaying for target material in a biological sample. This patent expires in November 2025 assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

A U.S. patent directed to a microflow apparatus. This patent will expire in May 2030 assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

•

A U.S. patent directed to a method of inhibiting cellular aggregation in a biologically active sample. This patent will expire in September 2031 assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

•

U.S. and European patent applications directed to a formulation to inactivate pathogens. Any patent issuing from these applications is expected to expire in 2041, not including any patent term adjustment or patent term extension and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

Government Regulation and Product Approval

Government authorities in the United States, at the federal, state and local level, and in other countries and jurisdictions, including the European Union (“EU”), extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, and import and export of pharmaceutical and medical device products. The processes for obtaining regulatory clearances, authorizations, or approvals in the United States and in foreign countries and jurisdictions, along with compliance with applicable statutes and regulations and other regulatory authorities, require the expenditure of substantial time and financial resources. ~~Our~~Nanoparticle ~~nanoparticle~~ oncology drug candidates ~~and our 188RNL-BAM device candidate~~ must receive regulatory approvals from the European Commission and the FDA and from other government authorities prior to sale of the product candidates in their respective jurisdictions.

Government authorities in the United States and in other countries also regulate clinical laboratories and clinical lab tests, including LDTs such as the CNSideTM Test. In order to perform clinical lab tests, report out results and bill payers for these tests, clinical labs must obtain and maintain certification under the federal Clinical Laboratories Improvement Amendments (“CLIA”) regulations and they also may be subject to licensure and regulation under certain state laws. Historically, the FDA exercised enforcement discretion with respect to LDTs and did not require these tests to be cleared or approved by FDA as long as they complied with CLIA standards. However, on May 6, 2024, the FDA issued a final rule in which it announced it was phasing out its general enforcement discretion approach so that LDTs manufactured by a laboratory will generally fall under the same enforcement approach as other medical devices; this phase out of enforcement discretion will take place over several years. As a result, CNSide Diagnostics may also be required to comply with these FDA regulations if FDA implements and enforces the final LDT rule, including, among other things, registration and listing, quality system regulations, and premarket authorization. Failure to comply with applicable FDA regulatory requirements may trigger a range of enforcement actions by the FDA, and may disqualify or delay a company from launching an LDT product, or prevent a company with an LDT on the marketing from continuing to sell their test.

FDA Approval Process

In the United States, pharmaceutical and medical device products are subject to extensive regulation by the FDA. Manufacturers of pharmaceutical and medical device products may also be subject to state and local regulation. The FDCA and other federal and state statutes and regulations govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling, and import and export of pharmaceutical and medical device products. Failure to comply with applicable U.S. requirements may subject a company to a variety of administrative or judicial sanctions, such as the imposition by the FDA or an institutional review board (“IRB”) of a clinical hold, FDA refusal to approve pending new drug applications (“NDAs”) or supplements, withdrawal of approval, untitled or warning letters, product recalls, import alerts, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties, and criminal investigation, penalties, or prosecution.

Pharmaceutical Product Approval

Table of Contents

Product development for a new pharmaceutical product or certain changes to an approved pharmaceutical product in the United States typically involves:

•

Completion of preclinical laboratory studies, formulation studies, and animal studies, some in compliance with the FDA’s Good Laboratory Practices (“GLP”) regulations, and the Animal Welfare Act administered and enforced by the United States Department of Agriculture;

•

Submission to the FDA of an IND to support human clinical testing, which must become effective before clinical testing may commence;

•

Approval by an IRB before each trial may be initiated at each clinical site;

•

Performance of adequate and well-controlled clinical trials under protocols submitted to the FDA and reviewed and approved by each IRB, conducted in accordance with federal regulations and current Good Clinical Practices (“GCP”) to establish the safety and effectiveness of the drug for each indication for which FDA approval is sought;

•

Submission of an NDA to the FDA that includes ~~substantial~~ evidence ofthat ~~safety~~the drug is safe for use under the conditions in the proposed labeling and substantial evidence of effectiveness from results of clinical trials, as well as the results of preclinical testing, detailed information about the chemistry, manufacturing and controls, and proposed labeling and packaging for the product;

•

~~Satisfactory~~Potential ~~completion~~FDA audit of anthe ~~FDA~~preclinical ~~Advisory~~and ~~Committee~~clinical ~~review,~~trial ifsites ~~applicable~~that generated the data in support of the NDA;

•

~~Potential~~Satisfactory completion of FDA ~~audit~~inspections of the ~~preclinical~~manufacturing ~~and~~facilities ~~clinical~~at ~~trial~~which ~~sites~~the ~~that~~product ~~generated~~candidate ~~the~~is ~~data~~produced into ~~support~~assess ofcompliance with cGMP and to assure that the ~~NDA~~facilities, methods and controls are adequate; and

•

Satisfactory completion of an FDA inspection of the manufacturing facilities at which the product candidate is produced to assess compliance with cGMP and to assure that the facilities, methods and controls are adequate; and

FDA review and approval of the NDA, including agreement on post-marketing requirements or commitments, if applicable.

Satisfaction of FDA pre-market approval requirements typically takes many years and the actual time required may vary substantially based upon the type, complexity, and novelty of the product or disease.

Preclinical tests include laboratory evaluation of product chemistry, formulation, and toxicity, as well as animal ~~trials~~studies to assess the characteristics and potential safety and efficacy of the product candidate. The conduct of some preclinical tests must comply with federal regulations and requirements, including as applicable, GLP and the Animal Welfare Act. The results of preclinical testing are submitted to the FDA as part of an IND along with other information, including information about product chemistry, manufacturing and controls, and a proposed clinical trial protocol. Additional preclinical tests, such as animal tests of reproductive toxicity and carcinogenicity, may continue after the IND is submitted. A 30-day waiting period after the submission of each IND is required prior to the commencement of clinical testing in humans. If the FDA has neither commented on nor questioned the IND within this 30-day period, the clinical trial proposed in the IND may begin.

Clinical trials involve the administration of the investigational drug product to healthy volunteers or patients under the supervision of a qualified investigator. Clinical trials must be conducted: (i) in compliance with federal regulations; (ii) in compliance with GCP, an international standard meant to protect the rights and health of patients and to define the roles of clinical trial sponsors, administrators, and monitors; as well as (iii) under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated. Each protocol involving testing on U.S. ~~patients~~study participants and subsequent protocol amendments must be submitted to the FDA as part of the IND. Foreign studies conducted under an IND generally must meet the same requirements that apply to studies being conducted in the United States. The informed written consent of each study patient must be obtained before the patient may begin participation in the clinical trial. The study protocol, study plan, and informed consent forms for each clinical trial must be reviewed and approved by an IRB for each clinical site, and the study must be conducted under the auspices of an IRB for each trial site. Investigators and IRBs must also comply with FDA regulations and guidelines, including those regarding oversight of study ~~patient~~participant informed consent, complying with the study protocol and investigational plan, adequately monitoring the clinical trial, and timely reporting of adverse events.

Clinical trials to support drug products for marketing approval are typically conducted in three sequential phases, but the phases may overlap. Phase 1 involves the initial introduction of the drug product into healthy human subjects or patients. In Phase 1 trials, the product is tested to assess safety, metabolism, pharmacokinetics, pharmacological actions, side effects associated with increasing doses, and, if possible, early evidence on effectiveness. Phase 2 usually involves trials in a limited patient population to determine the effectiveness of the drug for a particular indication, dosage tolerance, and optimal dosage, and to identify common adverse effects and safety risks. If a compound demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2 evaluations, Phase 3 trials are undertaken to obtain the additional information about clinical efficacy and safety in a larger number of patients, typically at geographically dispersed clinical trial sites, to permit the FDA to evaluate the overall benefit-risk relationship of the drug and to provide adequate information for the labeling of the product. In most cases, the FDA requires two adequate and well-controlled Phase 3 clinical trials to demonstrate the efficacy of the drug product. AUnder certain circumstances, a single Phase 3 trial ~~with~~may ~~other~~be ~~confirmatory~~sufficient ~~evidence~~when ~~may~~either be(1) ~~sufficient~~the intrial ~~certain~~is ~~instances.~~a ~~Additionally~~large, ~~post-approval~~multicenter ortrial ~~Phase~~demonstrating 4internal ~~studies~~consistency and ~~trials,~~a ~~may~~statistically bevery ~~conducted~~persuasive ~~after~~finding ~~initial~~of ~~marketing~~a ~~approval.~~clinically ~~These~~meaningful ~~studies~~effect ~~are~~on ~~often~~mortality, ~~used~~irreversible tomorbidity ~~gain~~or ~~additional~~prevention ~~information~~of ~~about~~a ~~use~~disease with a potentially serious outcome and confirmation of the ~~product~~result ~~for~~in ~~its~~a ~~approved~~second ~~indication,~~trial ~~and~~would ~~may~~be atpractically ~~times~~or beethically ~~required~~impossible byor (2) the ~~FDA~~single trial is supported by confirmatory evidence. Additionally, post-approval or Phase 4

~~The~~13 decision to suspend or terminate development of a product candidate may be made by either a health authority body, such as the FDA, by an IRB, or by a company for various reasons and during any phase of clinical trials. The FDA may order the temporary or permanent discontinuation of a clinical trial at any time or impose other sanctions if it believes that the clinical trial either is not being

16Table of Contents

~~conducted~~studies inand ~~accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients. In most cases, in addition to sponsor oversight, clinical~~ trials ~~are also overseen by an independent data safety monitoring board (“DSMB”)~~, ~~which is a separate, independent group of qualified experts organized by the trial sponsor to evaluate at designated points in time whether or not a trial~~ may ~~move~~be ~~forward~~conducted ~~and/or~~after ~~should~~initial bemarketing ~~modified~~approval. These ~~decisions~~studies are ~~based~~often onused ~~unblinded access~~ to ~~data~~gain ~~from~~additional ~~the~~information ~~ongoing~~about ~~trial~~use ~~and~~of ~~generally involve determinations regarding~~ the ~~benefit-risk~~product ~~ratio~~ for ~~study~~its ~~patients~~approved indication, and ~~the~~may ~~scientific~~at ~~integrity~~times ~~and~~be ~~validity~~required ofby the ~~clinical trial~~FDA.

InThe ~~addition~~decision to suspend or terminate development of a product candidate may be made by either a health authority body, such as the ~~manufacturer~~FDA, ofby an ~~investigational~~IRB, ~~drug~~or inby a ~~Phase~~company 2for orvarious ~~Phase~~reasons 3and during any phase of clinical ~~trial~~trials. ~~for~~The FDA may order the temporary or permanent discontinuation of a ~~serious~~clinical ~~disease~~trial at any time or ~~condition~~impose other sanctions if it believes that the clinical trial either is ~~required~~not being conducted in accordance with FDA requirements or presents an unacceptable risk to ~~make~~the ~~available~~clinical trial participants. In most cases, ~~such~~in asaddition to sponsor oversight, clinical trials are also overseen by ~~posting~~an onindependent ~~its~~data ~~website~~safety monitoring board (“DSMB”), ~~its~~which ~~policy~~is ona ~~evaluating~~separate, ~~and~~independent ~~responding~~group of qualified experts organized by the trial sponsor to ~~requests~~evaluate ~~for~~at ~~expanded~~designated points in time whether or not a trial may move forward and/or should be modified. These decisions are based on unblinded access to ~~such~~data ~~investigational~~from ~~drug~~the ongoing trial and generally involve determinations regarding the benefit-risk ratio for study patients and the scientific integrity and validity of the clinical trial.

~~After~~In ~~completion of the required clinical testing~~addition, ~~a drug product application is prepared and submitted to~~ the ~~FDA~~manufacturer ~~to request marketing approval for the product candidate in specific indications. FDA approval~~ of ~~the~~an investigational drug ~~product is required before marketing of the product may begin~~ in ~~the~~a ~~United~~Phase ~~States.~~2 ~~The~~or ~~drug~~Phase ~~product~~3 ~~must include all relevant results of preclinical,~~ clinical, ~~and~~trial ~~other~~for ~~testing and~~ a ~~compilation~~serious ofdisease ~~data~~or ~~relating to the product candidate’s pharmacology~~condition, ~~chemistry, manufacture, and controls, including negative~~ or ~~ambiguous results as well as positive findings. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and effectiveness~~ of ~~the~~an ~~product~~investigational ~~candidate to the satisfaction of the FDA. The cost of preparing and submitting a~~ drug ~~product~~that ~~application~~has isreceived ~~substantial.~~Fast ~~Under~~Track ~~the~~designation ~~Prescription~~or ~~Drug~~Breakthrough ~~User~~Therapy ~~Fee Act (“PDUFA”)~~designation, ~~the submission of most drug product applications~~ is ~~subject~~required to amake ~~substantial application user fee~~available, ~~and~~such ~~the~~as ~~applicant~~by ~~under~~posting anon ~~approved~~its ~~drug product is also subject to an annual program fee for each prescription product~~website, ~~subject to certain limited deferrals, waivers and reductions that may be available. These fees are typically increased annually. The FDA has 60 days from~~ its ~~receipt~~policy ~~of an NDA to determine whether the application will be accepted for filing based~~ on ~~the~~evaluating agency’s threshold determination that it is sufficiently complete to permit substantive review. The FDA may refuse to accept for filing any NDA that it deems incomplete or not properly reviewable at the time of submission, in which case the NDA will have to be updated and ~~resubmitted.~~responding ~~Once the submission is accepted for filing, the FDA begins an in-depth review. The FDA has agreed~~ to ~~certain~~requests performance goals in the review of NDAs. The FDA’s PDUFA review goal is to review 90% of priority applications within six months of filing and 90% of standard applications within 10 months of filing. Priority review may be granted to an application for aexpanded ~~product~~access ~~candidate that the FDA determines has the potential~~ to ~~treat~~such ainvestigational ~~serious or life-threatening condition and, if approved, would be a significant improvement in safety or effectiveness compared to available therapies~~drug. The review process for both standard and priority review may be extended by the FDA for three additional months to consider certain late-submitted information, or information intended to clarify information already provided in the submission.

After completion of the required clinical testing, an application is prepared and submitted to the FDA to request marketing approval for the product candidate in specific indications. FDA approval of the drug product is required before marketing of the product may begin in the United States. The drug product must include all relevant results of preclinical, clinical, and other testing and a compilation of data relating to the product candidate’s pharmacology, chemistry, manufacture, and controls, including negative or ambiguous results as well as positive findings. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and effectiveness of the product candidate to the satisfaction of the FDA. The cost of preparing and submitting a drug product application is substantial. Under the Prescription Drug User Fee Act (“PDUFA”), the submission of most drug product applications is subject to a substantial application user fee, and the applicant under an approved drug product is also subject to an annual program fee for each prescription product, subject to certain limited deferrals, waivers and reductions that may be available. These fees are typically increased annually. The FDA has 60 days from its receipt of an NDA to determine whether the application will be filed based on the agency’s threshold determination that it is sufficiently complete to permit substantive review. The FDA may refuse to file any NDA that it deems incomplete or not properly reviewable at the time of submission, in which case the NDA will have to be updated and resubmitted. Once the submission is filed, the FDA begins an in-depth review. The FDA has agreed to certain performance goals in the review of NDAs. The FDA’s PDUFA review goal is to review 90% of priority applications within six months of filing and 90% of standard applications within 10 months of filing. Priority review may be granted to an application for a product candidate that the FDA determines has the potential to treat a serious or life-threatening condition and, if approved, would be a significant improvement in safety or effectiveness compared to available therapies. The review process for both standard and priority review may be extended by the FDA for three additional months if the FDA determines that a major amendment has been submitted.

The FDA may also refer applications for drug candidates that present difficult questions of safety or efficacy, to an advisory committee—typically a panel that includes clinicians and other experts—for review, evaluation, and a recommendation as to whether the application should be approved. The FDA is not bound by the recommendation of an advisory committee, but it considers such recommendations carefully when making decisions. Before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. Additionally, the FDA will inspect the facility or the facilities at which the drug product is manufactured. The FDA will not approve the product unless compliance with cGMP is satisfactory and the NDA contains data that provides substantial evidence that the drug candidate is safe and effective in the intended indication.

After the FDA evaluates the NDA and the manufacturing facilities, it issues either an approval letter or a complete response letter. A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing, or information, in order for the FDA to reconsider the application. If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA may issue an approval letter. The FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included. Notwithstanding the submission of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval and deny approval of a resubmitted NDA.

An approval letter authorizes commercial marketing of the drug candidate with specific prescribing information for specific indications. As a condition of approval, the FDA may require a risk evaluation and mitigation strategy (“REMS,”) to help ensure that the benefits of the drug candidate outweigh the potential risks. REMS can include medication guides, communication plans for healthcare professionals, and elements to assure safe use (“ETASU”). ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring, and the use of patient registries. The requirement for a REMS can materially affect the potential market and profitability of the product. Moreover, FDA may require post-approval studies or trials and heightened surveillance to characterize or monitor the product’s safety or efficacy.

Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or problems are identified following initial marketing. For example, quality control and manufacturing procedures must conform, on an ongoing basis, to cGMP requirements, and the FDA periodically inspects manufacturing facilities to assess compliance with cGMP. Accordingly, manufacturers must continue to spend time, money and effort to maintain cGMP compliance. Changes to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval of a new NDA or NDA supplement before the change can be implemented. An NDA supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing NDA supplements as it does in reviewing an NDA.

1714

Table of Contents

new NDA or NDA supplement before the change can be implemented. An NDA supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing NDA supplements as it does in reviewing an NDA.

Expedited Programs

In the United States, a product may be granted Fast Track designation if it is intended for the treatment of a serious or life-threatening condition and ~~demonstrates~~nonclinical or clinical data demonstrate the potential to address unmet medical needs for such condition. With Fast Track designation, the sponsor may be eligible for more frequent opportunities to obtain the FDA’s feedback, and the FDA may initiate review of sections of an NDA before the application is complete. This rolling review is available if the applicant provides, and the FDA approves, a schedule for the remaining information. Even if a product receives Fast Track designation, the designation can be rescinded and provides no assurance that a product will be reviewed or approved more expeditiously than would otherwise have been the case, or that the product will be approved at all.

The FDA may designate a product candidate as a breakthrough therapy if it finds that the product candidate is intended, alone or in combination with one or more other product candidates or approved products, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the product candidate may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. For product candidates designated as breakthrough therapies, more frequent interaction and communication between the FDA and the sponsor can help to identify the most efficient path for clinical development. Product candidates designated as breakthrough therapies by the FDA may also be eligible for six month priority review. The receipt of a breakthrough therapy designation for a product candidate may not result in a faster development process, review or approval compared to product candidates considered for approval under conventional FDA procedures and, in any event, does not assure ultimate approval by the FDA. In addition, ~~even~~the ifFDA ~~one~~may orlater ~~more~~decide ofthat ~~our~~a product ~~candidates~~candidate ~~qualify~~that ashas ~~breakthrough~~been ~~therapies,~~designated ~~the~~as ~~FDA~~a ~~may~~breakthrough ~~later~~therapy ~~decide that the product candidates~~ no longer ~~meet~~meets the conditions for designation.

Accelerated approval under FDA regulations allows a product designed to treat a serious or life-threatening disease or condition that provides a meaningful therapeutic advantage over available therapies to be approved on the basis of either an intermediate clinical endpoint or a surrogate endpoint that is reasonably likely to predict clinical benefit. Approvals of this kind typically include requirements for confirmatory clinical trials to beverify ~~conducted~~and ~~with~~describe ~~due~~the ~~diligence~~clinical tobenefit. ~~validate~~These ~~the~~confirmatory ~~surrogate~~trials ~~endpoint~~must orbe ~~otherwise~~completed ~~confirm~~with ~~clinical~~due ~~benefit~~diligence and ~~for~~the ~~all~~FDA ~~promotional~~is ~~materials~~authorized to berequire ~~submitted~~that tosuch ~~the~~post-approval ~~FDA~~studies ~~for~~be ~~review~~underway prior to ~~dissemination.~~approval ~~The~~or ~~Consolidated~~within ~~Appropriations~~a ~~Act~~specific ~~(“CCA”)~~time ofperiod ~~2023~~after ~~amended~~ the ~~FDCA~~date toaccelerated ~~provide~~approval ~~FDA~~is ~~additional~~granted, ~~authorities~~and tothe ~~help~~agency ~~ensure~~has ~~timely~~issued ~~completion~~guidance ofas to what constitutes such ~~trials.~~a ~~Specifically,~~study ~~the~~being “underway.” The FDA is ~~now~~also ~~permitted~~required to ~~require~~specify ~~that~~conditions ~~such~~of any required post-approval ~~studies~~confirmatory betrial. ~~underway~~Sponsors ~~prior~~are required to submit progress reports for required post-approval orstudies ~~within~~and aany ~~specific~~conditions ~~time~~required ~~period~~by ~~after~~the FDA. The FDA may initiate enforcement action for the ~~date~~failure ~~accelerated~~to conduct with due diligence a required post-approval istrial, ~~granted~~including a failure to meet any required conditions, ~~and~~which may include enrollment targets, the ~~agency~~study ~~has~~protocol ~~issued~~and ~~guidance~~study asmilestones, tospecified ~~what~~by ~~constitutes~~the ~~such~~FDA, aor ~~study~~to ~~being~~submit ~~“underway~~timely reports.~~” The~~ ~~CCA~~All ofpromotional ~~2023~~materials ~~also~~for ~~established~~product ~~new~~candidates ~~procedures~~approved ~~for~~under ~~withdrawing~~accelerated ~~products~~approval ifregulations ~~they~~are ~~fail~~subject to ~~demonstrate~~prior areview ~~clinical~~by ~~benefit~~the FDA.

The FDA may grant priority review to a product candidate, which sets the target date for FDA action on the application at six months from FDA filing, or eight months from ~~the~~NDA ~~sponsor’s~~ submission. Priority Review may be granted where a product is intended to treat a serious or life-threatening disease or condition and, if approved, ~~has~~would ~~the potential to~~ provide a ~~safe~~significant ~~and~~improvement ~~effective~~in ~~therapy~~safety ~~where no satisfactory alternative therapy exists~~ or aeffectiveness ~~significant~~of ~~improvement~~the intreatment, ~~safety~~prevention, or ~~efficacy~~diagnosis ~~compared~~of tothat ~~available therapy~~condition. If criteria are not met for Priority Review, the standard FDA review period is ten months from FDA filing or 12 months from ~~sponsor~~NDA submission. Priority Review designation does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval.

Orphan Drug Designation

Under the Orphan Drug Act, the FDA may grant orphan drug designation to drug candidate products intended to treat a rare disease or condition, meaning one that affects fewer than 200,000 individuals in the United States, or if it affects more than 200,000 individuals in the United States, there is no reasonable expectation that the cost of developing and making a product available in the United States for such disease or condition will be recovered from sales of the product in the United States.

After the FDA grants orphan drug designation, the generic identity of the drug product and its potential orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process. However, orphan drug designation does entitle a party to financial incentives, such as opportunities for grant funding towards clinical trial costs, tax credits for certain research and user fee waivers under certain circumstances. In addition, if a product receives the first FDA approval for the ~~indication~~disease or condition for which it has orphan drug designation, the product is entitled to seven years of market exclusivity, which means the FDA may not approve any other application for the "same drug" for the same indication for a period of seven years, except in limited circumstances, such as a showing of clinical superiority over the product with orphan exclusivity. The FDA can revoke a product’s orphan drug exclusivity under certain circumstances, including when the product sponsor is unable to assure the availability of sufficient quantities of the product to meet patient needs. Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition, or the same drug for a different ~~disease or condition~~indication.

Table of Contents

Rare Pediatric Disease Priority Review Voucher Program

Under the Rare Pediatric Disease Priority Review Voucher program, the FDA may grant Rare Pediatric Disease designation for serious and life-threatening diseases that primarily affect children aged 18 years or younger and fewer than 200,000 individuals in the United States. The FDA may award a priority review voucher to the sponsor of an approved marketing application for a product that treats or prevents a Rare Pediatric Disease. The voucher entitles the sponsor to priority review of one subsequent marketing application.

the United States. The FDA may award a priority review voucher to the sponsor of an approved marketing application for a product that treats or prevents a Rare Pediatric Disease. The voucher entitles the sponsor to priority review of one subsequent marketing application.

A voucher may be awarded only for an application that:

•

is a human drug application for the prevention or treatment of a Rare Pediatric Disease and does not contain an active ingredient (including any ester or salt of the active ingredient) that has been previously approved in any other application;

•

FDA deems eligible for priority review;

•

is an original NDA or Biologics License Application (“BLA”);

•

relies on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population;

•

does not seek approval for an adult indication in the original rare pediatric disease product application; and

•

is approved after September 30, 2016.

Before NDA or ~~IND~~BLA approval or licensure, the FDA may designate a product in development as a product for a rare pediatric disease, but such designation is not required to receive a voucher.

To receive a rare pediatric disease priority review voucher, a sponsor must notify the FDA, upon submission of the NDA or ~~IND~~BLA, of its intent to request a voucher. If the FDA determines that the NDA or ~~IND~~BLA is a rare pediatric disease product application, and if the NDA or ~~IND~~BLA is approved or licensed, the FDA will award the sponsor of the NDA or ~~IND~~BLA a voucher upon approval of the NDA or ~~IND~~BLA. The FDA may revoke a rare pediatric disease priority review voucher if the product for which it was awarded is not marketed in the U.S. within 1 year of the product’s approval.

The voucher, which is transferable to another sponsor, may be submitted with a subsequent application and entitles the holder to priority review of ~~the~~that subsequent application. The sponsor submitting the priority review voucher must notify the FDA of its intent to submit the voucher with the application at least 90 days prior to submission of the application and must pay a priority review user fee in addition to any other required user fee. The FDA must take action on an application under priority review within six months of receipt of the application.

~~The Rare Pediatric Disease Priority Review Voucher began to sunset on December 20~~Currently, ~~2024, upon Congress’ failure to pass a continuing resolution package that included its reauthorization. Under~~ the ~~amended statutory sunset provisions, after December 20, 2024, the FDA may award a PRV for an approved~~ rare pediatric disease ~~product~~priority ~~application~~review ~~only~~voucher ifprogram ~~the~~will ~~sponsor~~sunset ~~has~~after ~~rare pediatric disease designation for the drug and if that designation was granted by December 20, 2024. After~~ September 30, ~~2026,~~2029. ~~the~~ FDA may not award any ~~rare pediatric disease~~ priority review vouchers. ~~Although~~under ~~there~~this ~~has~~program ~~been~~after ~~discussion~~September ~~of further extending the RPDPRV program~~30, ~~it is unclear if any such legislation will be adopted~~2029.

Disclosure of Clinical Trial Information

Sponsors of clinical trials of the FDA-regulated products are required to register and disclose certain clinical trial information. Information related to the product, patient population, phase of investigation, trial sites and investigators, and other aspects of the clinical trial is then made public as part of the registration. Sponsors are also obligated to discuss the results of their clinical trials after completion. Disclosure of the results of these trials can be delayed in certain circumstances for up to two years after the date of completion of the trial. Competitors may use this publicly available information to gain knowledge regarding the progress of development programs.

Pediatric Information

Under the Pediatric Research Equity Act (“PREA”), certain NDAs must include an assessment, ~~generally~~ based on clinical ~~trial~~ data, of the safety and effectiveness of the product candidate in relevant pediatric populations. The FDA may waive or defer the requirement for a pediatric assessment, either at a company’s request or by its own initiative, including waivers for certain products not likely to be used in a substantial number of pediatric patients. Products with orphan drug designation are exempt from these requirements for orphan-designated indications with no formal waiver process required. ~~Any~~However, any original NDA submitted on or after August 18, 2020 for a new active ingredient must contain reports on molecularly targeted pediatric cancer investigations, unless the requirement is waived or deferred, if the drug that is the subject of the application is intended for the treatment of an adult cancer and is directed at a molecular target that the FDA has determined is substantially relevant to the growth or progression of a pediatric cancer. This requirement applies even if the adult cancer indication does not occur in the pediatric population, and even if the drug is for an adult indication for which orphan designation has been granted.

even if the adult cancer indication does not occur in the pediatric population, and even if the drug is for an adult indication for which orphan designation has been granted.

Patent Term Restoration

After approval, owners of relevant drug patents may apply for up to a five-year patent extension as compensation for patent term lost during product development and the FDA regulatory review process. The allowable patent term extension is calculated as one half of the drug’s testing phase—the time between the effective date of an IND and NDA submission—and all of the review phase—the time between NDA submission and approval, up to a maximum of five years. The time can be shortened if the FDA determines that the applicant did not pursue approval with due diligence. The total patent term after the extension may not exceed 14 years. 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. The United States Patent and Trademark Office (“USPTO”), in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.

Table of Contents

drug’s testing phase—the time between the effective date of an IND and NDA submission—and all of the review phase—the time between NDA submission and approval, up to a maximum of five years. The time can be shortened if the FDA determines that the applicant did not pursue approval with due diligence. The total patent term after the extension may not exceed 14 years. 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. The United States Patent and Trademark Office (“USPTO”), in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.

For patents that might expire during the application phase, the patent owner may request an interim patent extension. An interim patent extension increases the patent term by one year and may be renewed up to four times. For each interim patent extension granted, the post-approval patent extension is reduced by one year. The director of the USPTO must determine that approval of the drug covered by the patent for which a patent extension is being sought is likely. Interim patent extensions are not available for a drug for which an NDA has not been submitted.

Market Exclusivity

In the United States and elsewhere, certain regulatory exclusivities and patent rights can provide an approved drug product with protection from certain competitors’ products for a period of time and within a certain scope. In the United States, the Drug Price Competition and Patent Term Restoration Act of 1984 (“the Hatch-Waxman Act”) amended the FDCA to establish two abbreviated approval pathways for pharmaceutical products that are in some way follow-on versions of already approved products. In exchange, the Hatch-Waxman Act also provides certain periods of exclusivity for a branded drug product that would serve as a reference listing drug (“RLD”) for a generic drug applicant filing an abbreviated new drug application (“ANDA”) under section 505(j) of the FDCA or as a listed drug for an applicant filing an NDA under section 505(b)(2) of the FDCA. If such a product is a “new chemical entity” (“NCE”), ~~generally~~ meaning that the active moiety has never before been approved in any drug product, there is a period of five years from the product’s approval during which the FDA may not ~~accept~~receive ~~for~~or ~~filing~~file any ANDA or 505(b)(2) application for a drug with the same active moiety. However, there are circumstances under which the follow-on application can be submitted at four years, and there are provisions that operate to preclude approval of the application for an additional period of time. NCE exclusivity does not block approval of a “full” NDA (generally, an NDA in which the data are the sponsor’s or for which the sponsor has obtained a right of reference). A drug product that is not an NCE may qualify for a three-year period of exclusivity if its NDA contains new clinical data (other than bioavailability studies), derived from studies conducted by or for the sponsor, that were necessary for approval. In this instance, the three-year exclusivity period does not preclude receipt, filing or review of an ANDA or 505(b)(2) application; rather, the FDA is precluded from granting final approval to the ANDA or 505(b)(2) application during the three-year exclusivity period. This three-year exclusivity applies only to the conditions of approval that required submission of the clinical data.

Post-Approval Regulation

Once approved, drug products are subject to continuing extensive regulation by the FDA. If ongoing regulatory requirements are not met, or if safety problems occur after a product reaches market, the FDA may take actions to change the conditions under which the product is marketed, such as requiring labeling modifications, restricting distribution, or even withdrawing approval. In addition to FDA regulation, our business is also subject to extensive federal, state, local and foreign regulation.

Good Manufacturing Practices. ~~We rely and expect to continue to rely on third parties for the production of clinical and commercial quantities of our product candidates.~~ Companies engaged in manufacturing drug products or their components, including contract manufacturers, must comply with applicable cGMP requirements, which include requirements regarding organization and training of personnel, building and facilities, equipment, control of components and drug product containers, closures, production and process controls, packaging and labeling controls, holding and distribution, laboratory controls and records and reports. The FDA inspects equipment, facilities and manufacturing processes before approval and conducts periodic re-inspections after approval. If, after receiving approval, a company makes a material change in manufacturing equipment, location, or process (all of which are, to some degree, incorporated in the NDA), additional regulatory review and approval may be required. Failure to comply with applicable cGMP requirements or the conditions of the product’s approval may lead the FDA to take enforcement actions, such as issuing a warning letter, or to seek sanctions, including fines, civil penalties, injunctions, suspension of manufacturing operations, imposition of operating restrictions, withdrawal of FDA approval, seizure or recall of products, and criminal prosecution. Although we periodically monitor FDA compliance of the third parties on which we rely for manufacturing our product candidates, we cannot be certain that our present or future third-party manufacturers will consistently comply with cGMP or other applicable FDA regulatory requirements.

Sales and Marketing. Once a product is approved, the advertising, promotion and marketing of the product will be subject to regulation, including with regard to promotion to healthcare practitioners, direct-to-consumer advertising, communications regarding unapproved uses, industry-sponsored scientific and educational activities and promotional activities involving the internet. In addition to FDA restrictions on marketing of pharmaceutical products, state and federal fraud and abuse laws have been applied to restrict certain marketing practices in the pharmaceutical industry. Failure to comply with applicable requirements in this area may subject a company to adverse publicity, investigations and enforcement action by the FDA, the Department of Justice, the Office of the Inspector General of the Department of Health and Human Services, and/or state authorities. This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes drug products.

unapproved uses, industry-sponsored scientific and educational activities and promotional activities involving the internet. In addition to FDA restrictions on marketing of pharmaceutical products, state and federal fraud and abuse laws have been applied to restrict certain marketing practices in the pharmaceutical industry. Failure to comply with applicable requirements in this area may subject a company to adverse publicity, investigations and enforcement action by the FDA, the Department of Justice, the Office of the Inspector General of the Department of Health and Human Services, and/or state authorities. This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes drug products.

Other Requirements. Companies that manufacture or distribute drug products pursuant to approved NDAs must meet numerous other regulatory requirements, including adverse event reporting, submission of periodic reports, and record-keeping obligations.

Table of Contents

Medical Device Premarketing Authorization

Under the FDCA, unless a device is exempt or marketed under an FDA enforcement discretion, premarketing, clearance, authorization, or approval is required to commercially distribute a new medical device in the U.S. market. A new medical device could either be a device that has not previously received marketing authorization, clearance or approval in the US, or a previously authorized, cleared, or approved device that has been changed in such a way that would require a new marketing ~~application~~submission. Changes that could require a new marketing application submission for an existing device may relate to, but are not limited to, the intended use of the device, the indications for use, manufacturing, and technological characteristics or functionalities. The type of marketing authorization, clearance, or approval is generally linked to the classification of the device.

The FDA classifies medical devices into three classes based on risk. Regulatory control increases from Class I (lowest risk) to Class III (highest risk). As the risk of the device increases, so dodoes FDA’s requirements tofor ~~obtain~~premarket ~~market authorization~~review. Generally, all Class III and some Class II medical devices will require clinical testing to adequately demonstrate the safety and effectiveness of the device prior to FDA approval or clearance of the device for commercialization. The extent to which FDA is involved in the development of clinical trial protocols depends, in part, on whether the study is a significant risk (“SR”) study or a nonsignificant risk (“NSR”) study. Before testing begins, all clinical studies must obtain ~~Institutional Review Board (~~IRB) approval and for SR medical devices an Investigational Device Exemption (“IDE”) must be obtained from the FDA. This exemption allows for clinical testing while ensuring participant safety and adherence to ethical standards. Though the regulatory requirements for an NSR study are less burdensome than those for a SR study, all clinical trials can be time consuming and costly and may not result in our desired outcomes.

Class I devices are those for which safety and effectiveness can be reasonably assured by adherence to a set of regulations referred to as general controls, which require compliance with the applicable portions of FDA’s Quality Management System Regulation (~~QSR~~“QMSR”), facility registration and device listing, reporting of deaths, serious adverse events and certain malfunctions, which is referred to as medical device reporting, reporting of recalls (corrections and removals), and truthful and non-misleading labeling and promotional materials. Most Class I devices are exempt from the premarket notification requirements (i.e., 510(k)-exempt).

Laboratory Developed Devices

Government authorities in the United States and in other countries also regulate clinical laboratories and clinical lab tests, including LDTs. In order to perform clinical lab tests, report results and bill payers for these tests, clinical labs must obtain and maintain certification under the federal Clinical Laboratories Improvement Amendments (“CLIA”) regulations and they also may be subject to licensure and regulation under certain state laws. On May 6, 2024, the FDA issued a final rule amending the definition of an in vitro diagnostic (“IVD”) device to include tests manufactured by a clinical laboratory. This rule would have required LDTs to comply with the same general regulatory requirements as other medical devices. Two lawsuits challenging FDA’s authority to regulate LDTs—one by the American Clinical Laboratory Association and the other by the Association for Molecular Pathology—were filed in federal district courts in Texas in 2024 and were subsequently consolidated.. On March 31, 2025, the court issued an order vacating the final rule, thereby overturning the rulemaking’s associated requirements. The district court ruled that FDA lacks jurisdiction to regulate LDTs because they do not meet the definition of a medical device under the FDC Act. The government did not appeal.

Legislative proposals addressing the FDA’s oversight of LDTs have been previously introduced. For example, the VALID Act, introduced in 2021, in 2023 and again in 2025, would have established a new risk-based regulatory framework for in vitro clinical tests (“IVCTs”), a category which would have included IVDs, LDTs, collection devices and instruments used with such tests. It is unclear whether the court decision will renew interest in a legislative path for LDT regulation.

510(k) Clearance Process

Class II devices are those that are subject to general controls, as well as special controls, which can include performance standards, specialized labeling and post-market surveillance. Most Class II devices are subject to the premarket notification requirements or the 510(k) process. To obtain 510(k) clearance, a premarket notification, or 510(k), must be submitted to the FDA that demonstrates that the proposed medical device is substantially equivalent to a previously cleared medical device or a device commercially distributed prior to May 28, 1976, for which the FDA has not yet called for the submission of a PMA.

The previously cleared device is known as a predicate device. A proposed device is substantially equivalent to a predicate device if, with respect to the predicate device, it has the same intended use and has either (i) the same technological characteristics or (ii) different technological characteristics that do not raise different questions of safety and effectiveness.

If the FDA determines that a device is “not substantially equivalent” to a previously cleared device, for example, due to a finding of a lack of a predicate device, or that the proposed device has a new intended use or different technological characteristics that raise different questions of safety or effectiveness from the proposed predicate device, the device is automatically designated as a Class III device. The device sponsor must then fulfill more rigorous PMA requirements, or can request a risk-based classification determination for the device in accordance with the de novo process. As a result, FDA clearance requirements may extend the development process for a considerable length of time. If the FDA agrees that the proposed device is substantially equivalent to the predicate device proposed by the manufacturer, it will grant 510(k) clearance to commercially market the device.

De Novo Classification Process

~~For~~18 novel medical devices that are low to moderate risk and are not substantially equivalent to a predicate device, a manufacturer may request a risk-based classification determination for the device in accordance with de novo classification process. This procedure allows a de novo requester whose novel device is automatically classified into Class III to request down-classification of its medical device into Class I or Class II on the basis that the device presents low or moderate risk, rather than requiring the submission and approval of a PMA. A requestor may submit a de novo request for classification after receiving a “not substantially

21Table of Contents

For novel medical devices that are low to moderate risk and are not substantially equivalent to a predicate device, a manufacturer may request a risk-based classification determination for the device in accordance with de novo classification process. This procedure allows a de novo requester whose novel device is automatically classified into Class III to request down-classification of its medical device into Class I or Class II on the basis that the device presents low or moderate risk, rather than requiring the submission and approval of a PMA. A requestor may submit a de novo request for classification after receiving a “not substantially equivalent” determination in response to a 510(k) submission or, absent the prior submission of a 510(k), when the sponsor determines that there is no legally marketed device upon which to base a determination of substantial equivalence.

The FDA may reject the de novo request if it identifies a legally marketed predicate device that would be appropriate for a 510(k) or determines that the device is not low to moderate risk or that general controls would be inadequate, and special controls cannot be developed, to control the risks. In the event the FDA determines that the data and information submitted demonstrate that general controls or general and special controls are adequate to provide reasonable assurance of safety and effectiveness, the FDA will grant the de novo request and a classification regulation will be established for the device type. When the FDA grants a de novo request for classification, the device is granted marketing authorization and can further serve as a predicate device for a future 510(k) submissions of that device type.

PMA Process

Class III devices include devices deemed by FDA to pose the greatest risk, such as life-supporting or life-sustaining devices, or implantable devices. With a few exceptions for certain types of devices classified into Class III that were in commercial distribution in the U.S. before May 28, 1976 and those placed into Class III by operation of law (i.e., novel devices not previously classified), Class III devices are subject to the pre-market approval (“PMA”) process which requires the manufacturer to independently demonstrate that a medical device is safe and effective for its intended use. This process is generally much more time-consuming and expensive than the 510(k) or de novo processes. The PMA process involves a complex and lengthy testing process that is subject to review by the FDA and may require several years to complete. The sponsor may need to first obtain an investigational device exemption (for significant risk devices), known as an IDE, in order to conduct extensive clinical testing of the device to obtain the necessary clinical data for submission to the FDA. Prior to obtaining approval, the manufacturer typically undergoes a bioresearch monitoring (“BIMO”) audit of the supporting clinical trial and a manufacturing audit, which may raise concerns that could lengthen the process and potentially raise unforeseen issues that undermine the approvability of the product. The FDA may also require review by an advisory panel, which can further lengthen the process.

The FDA will approve a PMA only if after evaluating the supporting technical data it finds that the PMA contains sufficient, valid scientific evidence to ~~assure~~establish a reasonable assurance that the device is safe and effective for its intended use(s). This approval may be granted with post-approval requirements including inspection of manufacturing facilities, additional patient follow-up for an indefinite period of time, and/or a post-approval clinical study or studies.

Exempt Devices

If a manufacturer’s device falls into a generic category of Class I or Class II devices that FDA has exempted by regulation, a premarket notification is not required before marketing the device in the U.S. (most Class I devices, and some Class II devices, are 510(k)-exempt.) Manufacturers of such devices are required to comply with FDA’s general controls, including FDA’s establishment registration and device listing requirements. Some 510(k)-exempt devices are also exempt from ~~QSR~~QMSR requirements, except for the ~~QSR~~QMSR’s ~~complaint~~requirements ~~handling~~relating to records and ~~recordkeeping~~complaint ~~requirements~~files.

Device Modifications post-clearance or approval

Medical devices can be marketed only for the indications for which they are cleared, authorized or approved. After a device has received 510(k) clearance for a specific intended use, any change or modification that significantly affects its safety or effectiveness, such as a significant change in the design, materials, method of manufacture or intended use, may require a new 510(k) clearance or, depending on the modification, a de novo classification request or PMA approval. The determination as to whether or not a modification could significantly affect the device’s safety or effectiveness is initially left to the manufacturer using available FDA guidance; however, the FDA may review this determination to evaluate the regulatory status of the modified product at any time and may, if it disagrees with the manufacturer’s determination, require the manufacturer to cease marketing and possibly recall the modified device until a new 510(k) clearance, de novo authorization or PMA approval is obtained. The manufacturer may also be subject to enforcement action, including significant regulatory fines or penalties for marketing a modified device without the requisite pre-marketing authorization.

Postmarket Requirements

After a device is cleared or approved for commercial distribution, numerous federal and state regulatory requirements apply. These include ~~product~~device listing and establishment registration requirements, which help facilitate FDA inspections and other regulatory actions. ~~Manufacturing~~Medical ~~sites~~device establishments are subject to periodic inspection by the FDA for compliance with applicable FDA regulatory requirements, including the FDA's ~~Quality~~QMSR, ~~System~~which ~~Regulations~~covers, ~~which~~among ~~cover~~other things, the procedures and documentation of the risk management, design, testing, production, control, quality assurance, labeling, packaging, sterilization, storage and shipping of medical devices; the Medical Device Reporting regulation, which requires that manufacturers and initial importers report to the FDA if a device they manufactured or imported may have caused or contributed to a death or serious injury or malfunctioned in a way that would likely cause or contribute to a death or serious injury if the malfunction were to recur; and the Reports of Corrections and Removals regulation, which requires manufacturers ~~to report recalls~~ and ~~field corrective actions to the FDA if initiated to reduce a risk to health posed by the device or to remedy a violation of the FDCA.~~

In19 addition, labeling and promotional activities are subject to scrutiny by the FDA and, in certain circumstances, by the Federal Trade Commission. Medical devices that are approved or cleared by the FDA may not be promoted for unapproved or uncleared uses, otherwise known as “off-label” promotion. The FDA and other agencies actively enforce the laws and regulations prohibiting the

22Table of Contents

~~promotion~~importers ofto ~~off-label~~report ~~uses,~~recalls and afield ~~company~~corrective ~~that~~actions ~~is found~~ to ~~have~~the ~~improperly~~FDA ~~promoted~~if ~~off-label~~initiated ~~uses~~to ~~may~~reduce bea ~~subject~~risk to ~~significant~~health ~~liability,~~posed ~~including~~by ~~substantial~~the ~~monetary~~device ~~penalties~~or ~~and~~to ~~criminal~~remedy ~~prosecution~~a violation of the FDCA.

IfIn ~~the~~addition, ~~FDA~~labeling ~~believes~~and ~~that~~promotional aactivities ~~company~~are issubject ~~not~~to inscrutiny ~~compliance~~by ~~with~~the ~~applicable~~FDA ~~regulations~~and, itin ~~may~~certain ~~issue a non-public untitled letter or a public warning letter~~circumstances, ~~institute~~by ~~proceedings~~the toFederal ~~detain~~Trade orCommission. ~~seize~~Medical ~~products,~~devices ~~issue~~that aare ~~recall or market withdrawal order~~approved, ~~impose~~authorized ~~operating restrictions including total~~ or ~~partial~~cleared ~~suspension~~by ~~of production or distribution, enjoin future violations, assess civil penalties against~~ the ~~company,~~FDA ~~its officers or its employees and~~ may ~~recommend~~not ~~criminal~~be ~~prosecution~~promoted tofor ~~the U.S. Department of Justice. Moreover~~unapproved, ~~after~~unauthorized ~~clearance~~ or ~~approval~~uncleared ~~is given~~uses, ifotherwise ~~the~~known ~~product~~as is“off-label” ~~shown~~promotion. toThe ~~be hazardous or defective, the~~ FDA ~~has~~and ~~the~~other ~~power~~agencies toactively ~~withdraw~~enforce the ~~clearance~~laws orand ~~approval,~~regulations asprohibiting the ~~case~~promotion ~~may~~of ~~be,~~off-label ~~or require us to change the device~~uses, ~~its~~and ~~manufacturing~~a ~~process~~company orthat ~~its~~is ~~labeling,~~found to ~~supply~~have ~~additional~~improperly ~~proof~~promoted ofoff-label ~~the~~uses ~~device’s~~may ~~safety~~be ~~and~~subject ~~effectiveness or~~ to ~~recall,~~significant ~~repair~~liability, ~~replace~~including ~~the~~substantial ~~device~~monetary orpenalties ~~refund~~and ~~the~~criminal ~~cost of the medical device~~prosecution.

If the FDA believes that a company is not in compliance with applicable regulations, it may issue a non-public untitled letter or a public warning letter, institute proceedings to detain or seize products, issue a recall or market withdrawal order, impose operating restrictions including total or partial suspension of production or distribution, enjoin future violations, assess civil penalties against the company, its officers or its employees and may recommend criminal prosecution to the U.S. Department of Justice. Moreover, after clearance, authorization, or approval is given, if the product is shown to be hazardous or defective, the FDA has the power to withdraw the clearance, authorization, or approval, as the case may be, or require us to change the device, its manufacturing process or its labeling, to supply additional proof of the device’s safety and effectiveness or to recall, repair, replace the device or refund the cost of the medical device.

Other U.S. Healthcare Laws and Compliance Requirements

In the United States, ~~our~~ activities of drug and device manufacturers are potentially subject to regulation by various federal, state and local authorities in addition to the FDA, including but not limited to, the Centers for Medicare and Medicaid Services (“CMS”), other divisions of the U.S. Department of Health and Human Services (e.g., the Office of Inspector General), the U.S. Department of Justice (“DOJ,”) and individual U.S. Attorney offices within the DOJ, and state and local governments. For example, sales, marketing and scientific/educational grant programs must comply with the anti-fraud and abuse provisions of the Social Security Act, the false claims laws, the privacy provisions of the Health Insurance Portability and Accountability Act and its implementing regulations (“HIPAA”), and similar state laws, each as amended. Clinical laboratory testing also must comply with the federal CLIA regulations and certain state licensure and other regulations, including restrictions related to billing for such tests.

The federal Anti-Kickback Statute prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting or receiving any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any item or service reimbursable under Medicare, Medicaid or other federal healthcare programs. The term remuneration has been interpreted broadly to include anything of value. The Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers, and formulary managers on the other. Liability under the Anti-Kickback Statute may be established without proving actual knowledge of the statute or specific intent to violate it. In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal civil False Claims Act. Although there are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution, the exceptions and safe harbors are drawn narrowly. Practices that involve remuneration that may be alleged to be intended to induce prescribing, purchasing or recommending a product or services may be subject to scrutiny if they do not qualify for an exception or safe harbor. Failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se illegal under the Anti-Kickback Statute. Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances. Our practices may not in all cases meet all of the criteria for protection under a statutory exception or regulatory safe harbor.

The civil monetary penalties statute imposes penalties against any person or entity who, among other things, is determined to have presented or caused to be presented a claim to a federal health program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent.

The federal civil False Claims Act prohibits, among other things, any person or entity from knowingly presenting, or causing to be presented, claims for payment of government funds, including Medicare or Medicaid, that are false or fraudulent, or knowingly making, using, or causing to be made or used a false record or statement material to an obligation to pay or transmit money to the federal government, or knowingly concealing or improperly avoiding or decreasing an obligation to pay money to the federal government.. Recently, several pharmaceutical and other healthcare companies have been prosecuted under these laws for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. Other companies have been prosecuted for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, and thus generally non-reimbursable, uses. Clinical laboratories may face enforcement under the federal civil False Claims Act related to the claims submitted for payment of government funds, including Medicare or Medicaid. Actions under the False Claims Act may be brought by the federal government or as a qui tam action by a private individual in the name of the government.

HIPAA created federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any money or property owned by, or under the control or custody of, any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up by trick, scheme or device, a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

2320

Table of Contents

covering up by trick, scheme or device, a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

Also, many states have similar fraud and abuse statutes or regulations that apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor. We may be subject to data privacy and security regulations by both the federal government and the states in which we conduct our business. HIPAA imposes requirements relating to the privacy, security and transmission of protected health information. In addition, state laws govern the privacy and security of personal information and health information in specified circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

Additionally, the federal Physician Payments Sunshine Act within the Affordable Care Act (“ACA”), and its implementing regulations, require that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report information related to certain payments or other transfers of value made or distributed to physicians, certain advanced practice professionals and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians, advanced practice professionals, and teaching hospitals and to report annually certain ownership and investment interests held by physicians and their immediate family members. The reported data are posted in searchable form on a public website on an annual basis. Failure to submit required information may result in civil monetary penalties.

In order to distribute products commercially, we must comply with state laws that require the registration of manufacturers and wholesale distributors of drug, device, and biological products in a state, including, in certain states, manufacturers and distributors who ship or sell products into the state even if such manufacturers or distributors have no place of business within the state. Some states also impose requirements on manufacturers and distributors to establish the pedigree of product in the chain of distribution, including some states that require manufacturers and others to adopt new technology capable of tracking and tracing product as it moves through the distribution chain. Several states have enacted legislation requiring pharmaceutical and biotechnology companies to establish marketing compliance programs, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities, and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician prescribing data to pharmaceutical and biotechnology companies for use in sales and marketing, and to prohibit certain other sales and marketing practices. All of our activities are potentially subject to federal and state consumer protection and unfair competition laws.

If our operations are found to be in violation of any of the federal and state healthcare laws described above or any other governmental regulations that apply to us, we may be subject to penalties, including without limitation, civil, criminal and/or administrative penalties, damages, fines, disgorgement, exclusion from participation in government programs, such as Medicare and Medicaid, injunctions, private “qui tam” actions brought by individual whistleblowers in the name of the government, or refusal to allow us to enter into government contracts, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.

Coverage, Pricing and Reimbursement

~~Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which we obtain regulatory approval, or any clinical laboratory tests we may offer.~~ In the United States ~~and in other countries~~, ~~sales of any products for which we receive regulatory approval for commercial sale, or laboratory tests we offer for clinical use, will depend, in part, on the extent to which~~ third-party payors ~~provide coverage, and establish adequate reimbursement levels for such products and services. In the United States, third-party payors~~ include federal and state healthcare programs, private managed care providers, health insurers and other organizations. The process for determining whether a third-party payor will provide coverage for a product or service may be separate from the process for setting the price of a product or service, or for establishing the reimbursement rate that such a payor will pay for the product or service. Third-party payors may limit coverage to specific products on an approved list, also known as a formulary, which might not include all of the FDA-approved products for a particular indication. Third-party payors are increasingly challenging the price, examining the medical necessity and reviewing the cost-effectiveness of medical products, therapies and services, in addition to questioning their safety and efficacy. We may need to conduct expensive pharmaco-economic studies in order to demonstrate the medical necessity and cost-effectiveness of our product candidates, in addition to the costs required to obtain the FDA approvals. Our product candidates may not be considered medically necessary or cost-effective. A payor’s decision to provide coverage for a product or service does not imply that an adequate reimbursement rate will be approved. Further, one payor’s determination to provide coverage for a product or service does not assure that other payors will also provide coverage for the product or service. Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in development of the product or service.

Different pricing and reimbursement schemes exist in other countries. In the EU, governments influence the price of pharmaceutical products through their pricing and reimbursement rules and control of national health care systems that fund a large part of the cost of those products to consumers. Some jurisdictions operate positive and negative list systems under which products may only

be marketed once a reimbursement price has been agreed. To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical trials that compare the cost-effectiveness of a particular product candidate to currently available therapies. Other EU Member States allow companies to fix their own prices for medicines, but monitor and control company profits. Others adopt a system of reference pricing, basing the price or reimbursement level in their territories either on the pricing and reimbursement levels in other countries or on the pricing and reimbursement levels of medicinal products intended for the same therapeutic indication. Further, some EU Member States approve a specific price for the medicinal product or may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal on the market. The downward pressure on health care costs has become very intense. As a result, increasingly high barriers are being erected to the entry of new products. In addition, in some countries, cross-border imports from low-priced markets exert a commercial pressure on pricing within a country.

Health Technology Assessment (“HTA”) of medicinal products and certain medical devices is becoming an increasingly common part of the pricing and reimbursement procedures in some EU Member States, including those representing the larger markets. The HTA process, which is currently governed by national laws in each EU Member State, assesses the therapeutic, economic, and societal impact of a given medicinal product or medical device in the national healthcare system of the individual country. The outcome of an HTA will often influence the pricing and reimbursement status granted to these medicinal products or medical devices by the competent authorities of individual EU Member States. The extent to which pricing and reimbursement decisions are influenced by the HTA of a specific medicinal product or medical device varies between EU Member States. The EU HTA Regulation (EU) 2021/2282, which was adopted in December 2021 and entered into force in January 2022, aims to harmonize the clinical benefit assessment of HTA across the EU and applies as of January 12, 2025. It provides for common HTA tools, methodologies, and procedures and complements Directive 2011/24/EU on the application of patients’ rights in cross-border healthcare, under which a voluntary network of national authorities or bodies responsible for HTA in the individual EU Member States was established.

The marketability of any product candidates for which we receive regulatory approval for commercial sale may suffer if the government and third-party payors fail to provide adequate coverage and reimbursement. In addition, emphasis on managed care in the United States has increased and we expect will continue to increase the pressure on healthcare pricing. Coverage policies and third-party reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more or our products or services, less favorable coverage policies and reimbursement rates may be implemented in the future.

Healthcare Reform

The ACA has substantially changed some aspects of healthcare financing and delivery by both governmental and private insurers. The ACA has affected existing government healthcare programs and resulted in the development of new programs.

Among the ACA provisions of importance to the pharmaceutical and biotechnology industries, in addition to those otherwise described above, are the following:

•

an annual, nondeductible fee on any entity that manufactures or imports certain specified branded prescription drugs and biologic agents apportioned among these entities according to their market share in some government healthcare programs, that began in 2011;

•

an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program, to 23.1% and 13% of the average manufacturer price for most branded and generic drugs, respectively, which rebate amount is no longer subject to a cap effective January 1, 2024;

•

extension of manufacturers’ Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations;

•

expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to additional individuals beginning in 2014 and by adding new mandatory eligibility categories for individuals with income at or below 133% of the federal poverty level, thereby potentially increasing manufacturers’ Medicaid rebate liability;

•

expansion of the entities eligible for discounts under the 340B drug discount program; and

Table of Contents

•

a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.

The Tax Cuts and Jobs Act of 2017 eliminated certain requirements of the ACA, including the individual mandate. We cannot predict whether these challenges will continue or whether other proposals will be made or adopted, or what impact these efforts may have on us. It is possible that the ACA, as currently enacted or may be amended in the future, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, and new payment methodologies and in additional downward pressure on coverage and payment and the price that we receive for any approved product. Any reduction in reimbursement from Medicare or other government programs may result in a similar 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 products. We cannot be sure whether additional legislative changes will be enacted in the United States or outside of the United States, or whether regulatory changes, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of our product candidates, if any, may be.

25Other legislative changes relating to reimbursement have been adopted in the U.S. since the ACA was enacted. For example, the Budget Control Act of 2011, among other things, created the Joint Select Committee on Deficit Reduction to recommend to Congress proposals for spending reductions. The Joint Select Committee did not achieve a targeted deficit reduction, which triggered the legislation’s automatic reductions. In concert with subsequent legislation, this has resulted in aggregate reductions to Medicare payments to providers until 2032, unless additional Congressional action is taken.

~~reduction~~The inProtecting ~~payments~~Access ~~from~~to ~~private~~Medicare ~~payors.~~Act ~~The implementation~~ of ~~cost~~2014 ~~containment~~(“PAMA”) ~~measures~~changed orthe ~~other~~methodology ~~healthcare~~for ~~reforms~~setting ~~may~~Medicare ~~prevent~~reimbursement usrates ~~from~~for ~~being~~clinical ~~able~~laboratory totests. Rates ~~generate~~for ~~revenue,~~new ~~attain~~clinical ~~profitability~~laboratory ortests ~~commercialize~~are ~~our~~initially ~~products.~~set Weby ~~cannot~~CMS, bebut ~~sure~~ultimately ~~whether~~the ~~additional~~reimbursement ~~legislative~~rates ~~changes~~are ~~will~~based beon ~~enacted in~~ the ~~United~~weighted ~~States~~median ~~or outside~~ of ~~the~~rates ~~United~~paid ~~States,~~for orthe ~~whether~~test ~~regulatory~~by ~~changes~~private payers, ~~guidance~~which orlabs ~~interpretations~~are ~~will~~required bereport ~~changed,~~to orCMS ~~what~~at ~~the~~specific ~~impact~~intervals. ofFurther ~~such~~federal changes onthat affect the ~~marketing~~coverage ~~approvals~~and reimbursement of ~~our~~clinical ~~product~~lab ~~candidates,~~tests ~~if any,~~ may be implemented in the future.

~~Other~~Further, ~~legislative~~the ~~changes~~Inflation ~~relating~~Reduction toAct ~~reimbursement~~of ~~have~~2022 ~~been~~(“IRA”), ~~adopted~~among inother things, established a Medicare Part B and Part D inflation rebate scheme, under which, generally, manufacturers will owe rebates if the average sales price of certain Part B drugs or annual average manufacturer price of certain covered Part D drugs increases faster than the pace of inflation. The IRA also requires the U.S. ~~since~~Department ~~the~~of ~~ACA~~Health ~~was~~and ~~enacted.~~Human ~~For~~Services ~~example,~~(“HHS”) ~~the~~to ~~Budget~~directly ~~Control~~negotiate ~~Act~~the selling price of ~~2011,~~a ~~among~~statutorily ~~other~~specified ~~things,~~number ~~created~~of ~~the~~drugs ~~Joint~~and ~~Select~~biologics ~~Committee~~each onyear ~~Deficit~~that ~~Reduction~~CMS toreimburses ~~recommend~~under toMedicare ~~Congress~~Part ~~proposals~~B ~~for~~and ~~spending~~Part ~~reductions~~D. The ~~Joint~~negotiated ~~Select~~price ~~Committee~~may ~~did~~ not ~~achieve~~exceed a ~~targeted~~statutory ~~deficit~~ceiling ~~reduction,~~price. ~~which~~Only ~~triggered~~high-expenditure ~~the~~single-source ~~legislation’s~~drugs ~~automatic~~that ~~reductions.~~have Inbeen ~~concert~~approved for at least seven years (11 years for single-source biologics) can qualify for negotiation, with ~~subsequent~~the ~~legislation~~negotiated price taking effect two years after the selection year. For 2026, ~~this~~the ~~has~~first ~~resulted~~year in ~~aggregate~~which ~~reductions~~negotiated toprices become effective, CMS selected 10 high-cost Medicare ~~payments~~Part toD ~~providers.~~products ~~Sequestration~~in is2023, ~~currently~~negotiations ~~set~~began atin 2%2024, and ~~will~~the ~~increase~~negotiated tomaximum ~~2.25%~~fair price for ~~the~~each ~~first~~product ~~half~~has ofbeen ~~fiscal~~announced. ~~year~~In ~~2030~~addition, toCMS 3%has ~~for~~selected and announced the ~~second~~negotiated ~~half~~maximum offair ~~fiscal~~price ~~year~~for ~~2030~~15 additional Medicare Part D drugs, ~~and~~which towill 4%become effective for ~~the~~negotiated ~~remainder~~maximum fair pricing in 2027. For 2028, CMS selected an additional 15 drugs, comprised of ~~the~~drugs ~~sequestration~~covered ~~period~~under ~~that~~Medicare ~~lasts~~Part ~~through~~D and, for the first ~~six~~time, ~~months~~drugs ofpayable ~~fiscal~~under ~~year~~Medicare ~~2031~~Part B. AsFor ~~long~~2029 asand ~~these~~subsequent ~~cuts~~years, ~~remain~~20 inPart ~~effect~~B or Part D drugs will be selected. Currently, ~~they~~a ~~could~~drug ~~adversely~~or ~~impact~~biological ~~payment~~product that has an orphan drug designation for ~~any~~only ~~products~~one werare ~~may~~disease ~~commercialize~~or incondition will be excluded from the ~~future.~~IRA’s Weprice ~~expect~~negotiation requirements, but loses that exclusion if it has designations for more than one rare disease or condition, or if is approved for an indication that is not within that single designated rare disease or condition, unless such additional ~~federal~~designation ~~healthcare~~or ~~reform~~such ~~measures~~disqualifying ~~will~~approvals beare ~~adopted~~withdrawn inby the ~~future~~time CMS evaluates the drug for selection for negotiation. However, ~~any~~as a result of ~~which~~a ~~could~~statutory ~~limit~~amendment enacted in July 2025, beginning with the ~~amounts~~2028 ~~that~~negotiated ~~federal~~price ~~and~~applicability ~~state~~year, ~~governments~~a ~~will~~drug ~~pay~~may be designated for ~~healthcare~~more ~~products~~than one rare disease or condition and ~~services~~still be excluded from price negotiation, as long as the only approved indications are for such rare diseases or conditions. The IRA further made several changes to the Medicare Part D benefit, including a limit on annual out-of-pocket costs, and replacement of the coverage gap discount program with a new manufacturer discount program beginning in ~~turn~~2025. ~~could~~The ~~significantly~~IRA ~~reduce~~permits the ~~projected~~Secretary ~~value~~of HHS to implement many of ~~certain~~these ~~development~~provisions ~~projects~~through ~~and~~guidance, ~~reduce~~as ~~our~~opposed ~~profitability~~to regulation, for the initial years. Manufacturers that fail to comply with the IRA may be subject to various penalties, some significant, including civil monetary penalties.

~~The~~Further, ~~Protecting~~at ~~Access to Medicare Act of 2014 (“PAMA”) changed~~ the ~~methodology for setting Medicare reimbursement rates for clinical laboratory tests~~U. ~~Rates~~S. ~~for~~state ~~new clinical laboratory tests are initially set by CMS~~level, ~~but~~legislatures ~~ultimately the reimbursement rates~~ are ~~based~~increasingly onenacting ~~the~~laws ~~weighted~~and ~~median~~implementing ofregulations ~~rates~~designed ~~paid~~to ~~for~~control ~~the~~pharmaceutical ~~test~~and bybiological ~~private~~product ~~payers~~pricing, ~~which~~including ~~labs~~price ~~are~~or ~~required~~reimbursement ~~report~~constraints, todiscount ~~CMS~~requirements, atmarketing ~~specific~~cost ~~intervals.~~disclosure ~~Further~~and ~~federal~~price ~~changes~~increase ~~that~~transparency ~~affect~~reporting, ~~the coverage~~ and ~~reimbursement~~programs ofdesigned ~~clinical~~to ~~lab~~encourage ~~tests~~importation ~~may~~from beother ~~implemented~~countries ~~in the future~~ and ~~may~~bulk ~~adversely affect our business~~purchasing.

Further, the Inflation Reduction Act of 2022 (“IRA”), among other things, established a Medicare Part B and Part D inflation rebate scheme, under which, generally, manufacturers will owe rebates if the average sales price of certain Part B drugs or annual average manufacturer price of certain covered Part D drugs increases faster than the pace of inflation. The IRA also created a drug price negotiation program under which the prices for certain Medicare units of certain high Medicare spend drugs and biologics without generic or biosimilar competition will be capped by reference to, among other things, a specified non-federal average manufacturer price, starting in 2026. The IRA further made several changes to the Medicare Part D benefit, including a limit on annual out-of-pocket costs, and replacement of the coverage gap discount program with a new manufacturer discount program beginning in 2025.

Additional legislative changes, regulatory changes, or guidance could be adopted, which may impact the marketing approvals and reimbursement for our product candidates and service offerings. For example, there has been increasing legislative, regulatory, and enforcement interest in the United States with respect to drug pricing practices. There have been several Congressional inquiries and proposed and enacted federal and state legislation and regulatory initiatives designed to, among other things, bring more transparency to product pricing, evaluate the relationship between pricing and manufacturer patient programs, and reform government healthcare program reimbursement methodologies for drug products. If healthcare policies or reforms intended to curb healthcare costs are adopted or if we experience negative publicity with respect to pricing of our products or the pricing of pharmaceutical drugs generally, the prices that we charge for any approved products may be limited, our commercial opportunity may be limited and/or our revenues from sales of our products may be negatively impacted.

Government Price Reporting

Federal law requires manufacturers report the average sales price for certain drugs payable under Medicare Part B. Manufacturers calculate average sales price based on a statutorily defined formula as well as regulations and interpretations of the statute by CMS. CMS may use these submissions to determine payment rates for drugs under Medicare Part B. Moreover, manufacturers must pay refunds to Medicare for single source drugs or biologicals, or biosimilar biological products, reimbursed under Medicare Part B and packaged in single-dose containers or single-use packages, for units of discarded drug reimbursed by Medicare Part B in excess of 10 percent of total allowed charges under Medicare Part B for that drug. Manufacturers that fail to pay refunds could be subject to civil monetary penalties of 125 percent of the refund amount.

Table of Contents

Statutory or regulatory changes or CMS guidance could affect the pricing calculations for our product candidates, once approved and commercialized, and could negatively impact our results of operations. We further expect continued scrutiny on government price reporting and pricing more generally from Congress, agencies, and other bodies.

The Foreign Corrupt Practices Act

The Foreign Corrupt Practices Act (“FCPA,”) prohibits any U.S. individual or business from paying, offering, or authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of

influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities are listed in the United States to comply with accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.

Additional Regulation

In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect our business. These and other laws govern our use, handling and disposal of various biological, chemical and radioactive substances used in, and wastes generated by, our operations. If our operations result in contamination of the environment or expose individuals to hazardous substances, we could be liable for damages and governmental fines. We believe that we are in material compliance with applicable environmental laws and that continued compliance therewith will not have a material adverse effect on our business. We cannot predict, however, how changes in these laws may affect our future operations.

EU / Rest of World Government Regulation

In addition to regulations in the United States, we will be subject to a variety of regulations in other jurisdictions governing, among other things, marketing authorizations, regulatory approvals, clinical trials and any commercial sales and distribution of our product candidates. Whether or not we obtain FDA approval of a product, we must obtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical trials or marketing of the product in those countries. Certain countries outside of the United States have a similar process that requires the submission of a clinical trial application much like the IND prior to the commencement of human clinical trials. Once the clinical trial application is approved in accordance with a country’s requirements, clinical trial development may proceed.

The requirements and process governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country. In all cases, the clinical trials are conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

If we or our potential collaborators fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Clinical trials in the EU: In the EU a clinical trial application must be submitted for authorization to the competent national authority of each EU Member State in which the clinical trial is to be conducted. Furthermore, the applicant may only start a clinical trial at a specific study site after the competent ethics committee has issued a favorable opinion. The regulation of clinical trials in the EU recently changed. The EU Clinical Trials Regulation entered into force on January 31, 2022, repealing the previous EU Clinical Trials Directive (Directive (EC) 2001/20/EC) and the related national implementing provisions of the individual EU Member States. Under the EU Clinical Trials Directive sponsors had to submit clinical trial applications separately to each national competent authority and ethics committee in the countries where they intended to run a clinical trial. The EU Clinical Trials Regulation significantly simplified this application process, allowing sponsors to submit one single application via the platform ‘Clinical Trials Information System’ (CTIS) for approval to run a clinical trial in several EU Member States (as well as in Iceland, Liechtenstein and Norway). Applications through the CTIS are mandatory from January 31, 2023. Clinical trials authorized under the EU Clinical Trials Directive before January 31, 2023, could continue to be conducted under the EU Clinical Trials Directive until January 31, 2025 (from January 31, 2025, any trials approved under the EU Clinical Trials Directive that continue running need to comply with the EU Clinical Trials Regulation and their sponsors must have recorded information on them in the CTIS).

Marketing authorization in the EU: To obtain regulatory approval to commercialize a new medicinal product in the EU, we must submit a marketing authorization application (MAA) to the competent regulatory authority. In the EU, marketing authorization for a medicinal product can be obtained through a centralized, mutual recognition, decentralized procedure, or the national procedure of an individual EU Member State. A marketing authorization, irrespective of its route to authorization, may be granted only to an applicant established in the EU.

The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid for all 27 EU Member States, Iceland, Liechtenstein and Norway. Under the centralized procedure, the Committee for Medicinal Products for Human Use (the “CHMP”) established at the European Medicines Agency (EMA) is responsible for conducting the initial assessment of a product. The maximum timeframe for the evaluation of an MAA is 210 days. This period excludes clock stops during which additional information or written or oral explanation is to be provided by the applicant in response to questions posed by the CHMP. Accelerated evaluation might be granted by the CHMP in exceptional cases, such as when a medicinal product is expected to

be of a major public health interest. A major public health interest defined by three cumulative criteria: (i) the seriousness of the disease (for example, heavy disabling or life-threatening diseases) to be treated; (ii) the absence or insufficiency of an appropriate alternative therapeutic approach; and (iii) the anticipation of high therapeutic benefit. If the CHMP accepts to review a medicinal product as a major public health interest, the time limit of 210 days will be reduced to 150 days. It is, however, possible that the CHMP can revert to the standard time limit for the centralized procedure if it considers that it is no longer appropriate to conduct an accelerated assessment.

Irrespective of the related procedure, at the completion of the review period the CHMP will provide a scientific opinion concerning whether or not a marketing authorization should be granted in relation to a medicinal product. This opinion is based on a review of the quality, safety, and efficacy of the product. Within 15 days of the adoption, the EMA will forward its opinion to the European Commission for its decision. Following the opinion of the EMA, the European Commission makes a final decision to grant a centralized marketing authorization. The centralized procedure is mandatory for certain types of medicinal products, including orphan medicinal products, medicinal products derived from certain biotechnological processes, advanced therapy medicinal products and medicinal products containing a new active substance for the treatment of certain diseases. This route is optional for certain other products, including medicinal products that are of significant therapeutic, scientific or technical innovation, or whose authorization would be in the interest of public or animal health at EU level.

Unlike the centralized authorization procedure, the decentralized marketing authorization procedure requires a separate application to, and leads to separate approval by, the authorities of each EU Member State in which the product is to be marketed. This application process is identical to the application that would be submitted to the EMA for authorization through the centralized procedure and must be completed within 210 days, excluding potential clock-stops, during which the applicant can respond to questions. The relevant EU Member State prepares a draft assessment and drafts of the related materials. The relevant EU Member States must decide whether to approve the assessment report and related materials. If an EU Member State cannot approve the assessment report and related materials due to concerns relating to a potential serious risk to public health, disputed elements may be referred to the European Commission, whose decision is binding on all EU Member States.

The mutual recognition procedure is similarly based on the acceptance by the relevant authorities of the EU Member States of the marketing authorization of a medicinal product by the relevant authorities of other EU Member States. The holder of a national marketing authorization may submit an application to the authority of an EU Member State requesting that this authority recognize the marketing authorization delivered by the authority of another EU Member State.

Innovative products that target an unmet medical need may be eligible for a number of expedited development and review programs in the EU, such as The Priority Medicines scheme, which provides incentives similar to the breakthrough therapy designation in the U.S. Such products are generally eligible for accelerated assessment and may also benefit from different types of fast-track approvals, such as a conditional marketing authorization or a marketing authorization under exceptional circumstances granted on the basis of less comprehensive clinical data than normally required (respectively in the likelihood that the sponsor will provide such data within an agreed timeframe or when comprehensive data cannot be obtained even after authorization).

The EU also provides opportunities for market exclusivity. For example, in the EU, upon receiving marketing authorization, new active substances generally receive eight years of data exclusivity and an additional two years of market exclusivity. If granted, data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic or biosimilar application. During the additional two-year period of market exclusivity, a generic or biosimilar marketing authorization can be submitted, and the innovator’s data may be referenced, but no generic or biosimilar product can be marketed until the expiration of the market exclusivity. The overall ten-year period will be extended to a maximum of 11 years if, during the first eight years of those 10 years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies. However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new active substance, and products may not qualify for data exclusivity.

In the EU, medicinal products: (a) that are used to diagnose, treat or prevent life-threatening or chronically debilitating conditions that affect no more than five in 10,000 people in the EU; or (b) that are used to treat or prevent life-threatening or chronically debilitating conditions and that, for economic reasons, would be unlikely to be developed without incentives; and (c) where no satisfactory method of diagnosis, prevention or treatment of the condition concerned exists, or, if such a method exists, the medicinal product would be of significant benefit to those affected by the condition, may be granted an orphan designation in the EU. The application for orphan designation must be submitted to the EMA’s Committee for Orphan Medicinal Products and approved by the European Commission before an application is made for marketing authorization for the product. Once authorized, orphan medicinal product designation entitles an applicant to financial incentives such as reduction of fees or fee waivers. In addition, orphan medicinal products are entitled to ten years of market exclusivity following authorization. During this ten-year period, with a limited number of exceptions, neither the competent authorities of the EU Member States, the EMA, or the European Commission are permitted to accept applications or grant marketing authorization for other similar medicinal products with the same therapeutic indication. However,

marketing authorization may be granted to a similar medicinal product with the same orphan indication during the ten-year period with the consent of the marketing authorization holder for the original orphan medicinal product or if the manufacturer of the original orphan medicinal product is unable to supply sufficient quantities. Marketing authorization may also be granted to a similar medicinal product with the same orphan indication if this latter product is safer, more effective or otherwise clinically superior to the original orphan medicinal product. The period of market exclusivity may, in addition, be reduced to six years if it can be demonstrated on the basis of available evidence that the original orphan medicinal product is sufficiently profitable not to justify maintenance of market exclusivity.

Combination products in the EU: For products and product candidates that combine medicinal products and device components (‘combination products’), the rules applicable vary depending on the specific combination. If the principal intended action of the product is achieved by the medicinal product, the product is considered a medicinal product that includes a medical device. The entire product is regulated under EU pharmaceutical legislation and must obtain a marketing authorization in the terms explained above. For the device part of the combination, the MAA should include a CE Certificate of Conformity for the device or, if the device is not CE-marked but would need to be certified if marketed separately, an opinion from an EU notified body on the conformity of the device with applicable requirements. If, however, the device is co-packaged or obtained separately from the medicinal product, it must be CE-marked under the EU medical devices legislation (Regulation (EU) 2017/745 on medical devices or the previous Directives 90/385/EEC and 93/42/EEC). Conversely, if the principal intended action in the product is achieved by the medical device (and the action of the medicinal product is only ancillary to that of the device), the entire product is regulated as a medical device and should be CE-marked under the EU medical devices legislation.

Revisions of the EU regulatory framework: The EU pharmaceutical legislation is currently under review. On April 26, 2023, the European Commission published its proposal to revise the EU pharmaceutical legislation, consisting of a new Directive and a new Regulation, which would revise and replace the existing general pharmaceutical legislation (Regulation 726/2004 and Directive 2001/83/EC) and the legislation on medicinal products for pediatric use and on orphan medicinal products (Regulation 1901/2006 and Regulation 141/2000/EC, respectively). Therefore, the provisions governing medicinal products in the EU may change in the future. The legislative process is ongoing and the final texts of the new acts are still unknown. Adoption is currently expected to occur in 2026, with implementation following thereafter.

EU in vitro diagnostic medical device legislation: In the EU, in vitro diagnostic medical devices (“IVD”) must currently comply with the General Safety and Performance Requirements laid down in Annex I to the In Vitro Diagnostic Devices Regulation (“IVDR”). Compliance with these requirements is a prerequisite to be able to affix the CE mark on products, without which they cannot be marketed or sold in the EU. To demonstrate compliance with the General Safety and Performance Requirements of the EU IVDR and obtain the right to affix the CE mark, IVD manufacturers must undergo a conformity assessment procedure, which varies according to the IVD’s classification. Apart from low risk medical devices (Class A non-sterile), in relation to which the manufacturer may issue an EC Declaration of Conformity based on a self-assessment of the conformity of its products with the General Safety and Performance Requirements, a conformity assessment procedure requires the intervention of a notified body, which is an organization designated by a Competent Authority of an EU Member State to conduct conformity assessments. Depending on the relevant conformity assessment procedure, the notified body would audit and examine the technical documentation and the quality system for the manufacture, design and final inspection of the IVDs. The notified body issues a CE Certificate of Conformity following successful completion of a conformity assessment procedure conducted in relation to the IVD and its manufacturer and their conformity with the General Safety and Performance Requirements. This Certificate and the related conformity assessment process entitles the manufacturer to affix the CE mark to its IVD after having prepared and signed a related EC Declaration of Conformity. Notified bodies must be designated by the authority responsible for notified bodies in the relevant EU Member State to conduct assessment procedures for IVDs in accordance with the EU IVDR. The time required to obtain a CE Certificate of Conformity from a notified body in the EU is lengthy and may be unpredictable. On average, the time-to-certification under the IVDR for all IVD categories ranges between 13 and 18 months.

Besides its involvement in the initial conformity assessment procedure, the Notified Body is required to carry out an annual audit (surveillance audit) and is also required to randomly perform unannounced audits at least once every five years. The quality management system and technical documentation of manufacturers will be required to be recertified periodically, as CE Certificates of Conformity issued by a Notified Body remain valid only for the period indicated in them, in no case exceeding five years. The EU IVDR also provides various requirements relating to post-market surveillance and vigilance, including the obligation for manufacturers to implement a post-market surveillance system. Once an IVD is on the EU market, manufacturers must comply with certain vigilance requirements, such as reporting serious incidents and field safety corrective actions (even those occurring outside the EU) to the relevant competent authorities.

Employees and Human Capital

As of December 31, ~~2024~~2025, we had 2128 full-time employees. Of these full-time employees, 1110 were engaged in research and development and 1018 were engaged in management, finance and administration. From time to time, we also employ independent contractors to support our operations. Our employees are not represented by any collective bargaining agreements and we have never experienced an organized work stoppage.

contractors to support our operations. Our employees are not represented by any collective bargaining agreements and we have never experienced an organized work stoppage.

We believe that we must offer and maintain market competitive compensation and benefit programs for our employees in order to attract and retain qualified personnel. In addition to cash compensation, we provide equity compensation, a company-matched 401(k) Plan, healthcare and insurance benefits, health savings and flexible spending accounts, paid time off, family leave, and employee assistance programs.

Corporate Information

We were initially formed as a California general partnership in July 1996 and incorporated in the State of Delaware in May 1997. We were formerly known as Cytori Therapeutics, Inc., before that as MacroPore Biosurgery, Inc. and before that as MacroPore, Inc. On July 20, 2019, we changed our name from Cytori Therapeutics, Inc. to Plus Therapeutics, Inc.

Our corporate offices are located at ~~2710~~6420 ~~Reed~~Levit ~~Road~~Green Boulevard, Suite ~~160~~210, Houston, TX ~~77051~~77021. Our telephone number is (737) 255-7194. We maintain a website at the following address: www.plustherapeutics.com. The information on the Company’s website is not incorporated by reference in this report. We make available on or through our website certain reports and amendments to those reports that we file with or furnish to the SEC in accordance with the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These include our Annual Reports on Form 10-K, our Quarterly Reports on Form 10-Q (“Form 10-Q”), and our Current Reports on Form 8-K. We make this information available on our website free of charge as soon as reasonably practicable after we electronically file the information with, or furnish it to, the SEC. In addition, we routinely post on the “Press Releases” page of our website news releases, announcements and other statements about our business and results of operations, some of which may contain information that may be deemed material to investors. Therefore, we encourage investors to monitor the “Press Releases” page of our website and review the information we post on that page.

The SEC maintains a website that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC at the following address: http://www.sec.gov.

Table of Contents

Risk Factor Summary

•

Uncertainties relating to our ability to fund our operations raises substantial doubt about our ability to continue as a going concern.

•

We could be delisted from Nasdaq for failure to comply with the Minimum Stockholders’ Equity Requirement, the Minimum Bid Requirement or other applicable continued listing requirements and standards of Nasdaq, which would seriously harm the liquidity of our stock and our ability to raise capital.

•

If we fail to maintain proper and effective internal controls, our ability to produce accurate financial statements on a timely basis could be impaired.

•

Our future success is in large part dependent upon our ability to successfully develop our nanomedicine platform and commercialize rhenium (186Re) obisbemeda and 188RNL-BAM and any failure to do so could significantly harm our business and prospects.

•

If we are unable to successfully partner with other companies to commercialize our product candidates, our business could materially suffer.

•

Clinical trial results may fail to support approval of our product candidates.

•

If third parties we engage are not able to successfully perform, we may not be able to successfully complete clinical development, obtain regulatory approval or commercialize our product candidates and our business could be substantially harmed.

•

We may have difficulty enrolling, or fail to enroll patients in our clinical trials, which could delay or prevent clinical trials of our drug candidates.

•

If a particular product candidate causes significant adverse events, then we may be unable to receive regulatory approval or market acceptance for such product candidate.

•

If our product candidates and technologies receive regulatory approval but do not achieve broad market acceptance, especially by physicians, the revenue that we generate will be limited.

•

All potential applications of our product candidates are investigational, which subjects us to development and marketing risks.

•

Table of Contents

•

The future regulatory processes that will be applicable to Laboratory Developed Tests (LDTs) are uncertain and may prevent us from obtaining required authorizations for the commercialization of our products and/or introduce additional costs associated with those products.

•

If we experience an interruption in supply from a material sole source supplier, our business may be harmed.

•

We may engage in strategic transactions that could impact our liquidity, increase our expenses, and present significant distractions to our management.

•

We must maintain quality controls and compliance with manufacturing standards.

•

If we are unable to identify, hire and/or retain key personnel, we may not be able to sustain or grow our business.

•

We face potential product liability exposure, and if successful claims are brought against us, we may incur substantial liability if our insurance coverage for those claims is inadequate.

•

We may not be successful in our efforts to develop, fully utilize and monetize the CNSide diagnostic portfolio.

•

Clinical laboratories are highly regulated and if we are unable to maintain compliance with these regulations, or if the regulations change in ways that make it more difficult or costly to comply, our financial condition and our business may be harmed.

•

Our relationships with customers, healthcare providers, including physicians, and third-party payors are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false claims 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.

•

The diagnostic testing industry is subject to rapid change, which could make our current or future products obsolete.

•

Our success depends in part on our ability to protect our intellectual property.

•

If we do not obtain patent term extension for any product candidates we may develop, our business may be materially harmed.

•

We may not be able to protect our trade secrets.

•

We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.

•

Our stockholders may experience substantial dilution in the value of their investment if we issue additional shares of our capital stock.

•

The market price of our common stock may be volatile and fluctuate significantly, which could result in substantial losses for stockholders.

•

We may be or become the target of securities litigation, which is costly and time-consuming to defend.

•

Our charter documents contain anti-takeover provisions.

•

We presently do not intend to pay cash dividends on our common stock.

•

Increased information technology security threats and more sophisticated and targeted computer crime could pose a risk to our systems, networks, and products.

Table of Contents

Item 1A. Risk Factors

The risk factors described below, as well as statements described elsewhere in this Form 10-K, including our audited Financial Statements and the related notes and “Management’s Discussion and Analysis of Financial Conditions and Results of Operations,” or in other SEC filings, describe risks that could materially and adversely affect our business, financial condition, and results of operations, which could also cause the trading price of our equity securities to decline. These risks are not the only risks that we face. Our business, financial condition and results of operations could also be affected by additional factors that are not presently known to us or that we currently consider to be immaterial to our operations.

Risks Related to our Financial Position and Capital Requirements

We have generated negative cash flows from operations and have incurred net operating losses each year since we started business. For the year ended December 31, ~~2024~~2025, we incurred net losses of $1322.04 million and our net cash used in operating activities was $1020.68 million. As of December 31, ~~2024~~2025, our accumulated deficit was $~~493~~515.59 million. We expect to continue to incur net losses and negative cash flow from operating activities for at least the next twelve months. As our focus on development of nanomedicine and the development of therapeutic applications has increased, losses have resulted primarily from expenses associated with research and development and clinical trial-related activities, as well as general and administrative expenses. We expect to continue operating in a loss position and expect that recurring operating expenses will be at higher levels for the year ending December 31, ~~2025~~2026 as we perform clinical trials and other development activities for our nanomedicine product candidates.

Our ability to generate sufficient revenue from any of our products, product candidates or technologies to achieve profitability will depend on a number of factors including, but not limited to:

•

our ability to manufacture, test and validate our product candidates or clinical tests in compliance with applicable laws and as required for submission to applicable regulatory bodies;

•

our or our partners’ ability to successfully complete clinical trials of our product candidates;

•

our ability to obtain necessary regulatory approvals for our product candidates;

•

our or our partners’ ability to negotiate and receive favorable reimbursement for our product candidates, including for our product candidates that have been granted or may be granted orphan drug status or otherwise command currently anticipated pricing levels;

•

our ability to negotiate favorable arrangements with third parties to help finance the development of, and market and distribute, our products and product candidates;

•

the degree to which our approved products are accepted in the marketplace; and

•

our success at commercializing our CNSideTM Portfolio.

Because of the numerous risks and uncertainties associated with our commercialization and product development efforts, we are unable to predict the extent of our future losses or when or if we will become profitable and it is possible we will never become profitable. If we do not generate significant sales from any of our product candidates that receive regulatory approval, there would be a material adverse effect on our business, results of operations, financial condition and prospects, which in turn could result in our inability to continue operations.

Our prospects must be evaluated in light of the risks and difficulties frequently encountered by emerging companies and particularly by such companies in rapidly evolving and technologically advanced biotech, pharmaceutical and medical device fields. In addition, our budgeted expense levels are based in part on our expectations concerning future research and development activities. We may be unable to reduce our expenditures in a timely manner to compensate for any unexpected events. Accordingly, unexpected events could have an immediate and material impact on our business and financial condition. From time to time, we have tried to update our investors’ expectations as to our operating results. If we revise any timelines we may give with respect to our clinical trials, it could materially harm our reputation and the market’s perception of us and could cause our stock price to decline.

Uncertainties relating to our ability to fund our operations ~~for at least the next 12 months~~ raises substantial doubt about our ability to continue as a going concern.

We received net proceeds of approximately $13.3 million, in the public offering that closed on January 15, 2026, allowing the Company to maintain a cash runaway until approximately 2027. As of December 31, ~~2024~~2025, we had an accumulated ~~stockholders’~~ deficit of approximately $~~493~~515.59 million, a working capital ~~deficit~~ of approximately $102.39 million, and approximately $313.61 million of cash and cash equivalents, restricted cash, and short-term investments to fund our operations and capital requirements. WeAbsent ~~do not currently have sufficient available liquidity to fund our operations for at least the next 12 months. Consequently, absent~~ further actions, these matters raise substantial doubt about our ability to continue as a going concern ~~within one year after the date that the financial statements in this Form 10-K are issued~~.

We have a history of generating losses and negative cash flows from operations. Our financial statements have been prepared under the assumption that we will continue as a going concern for the next twelve months. Our ability to continue as a going concern is dependent upon our ability to obtain additional debt, equity or other financing. Furthermore, we also could be required to seek funds through ~~arrangements with collaborative partners or otherwise that may require us to relinquish rights to some of our intellectual property or product candidates or otherwise agree to terms unfavorable to us.~~

Table of Contents

arrangements with collaborative partners or otherwise that may require us to relinquish rights to some of our intellectual property or product candidates or otherwise agree to terms unfavorable to us.

If we are unsuccessful in our efforts to raise any such additional capital, we would be required to take actions that could materially and adversely affect our business, including significant reductions in our research, development and administrative operations (including reduction of our employee base), possible surrender or other disposition of our rights to some technologies or product opportunities, delaying of our clinical trials or curtailing or ceasing operations.

We could be delisted from Nasdaq for failure to comply with the ~~minimum~~Minimum ~~stockholders~~Stockholders’ ~~equity~~Equity ~~continued~~Requirement, ~~listing~~the ~~requirement~~Minimum Bid Requirement or other applicable continued listing requirements and standards of Nasdaq, which would seriously harm the liquidity of our stock and our ability to raise capital.

Our common stock is currently listed on The Nasdaq Capital Market. In order to maintain that listing, we must maintain compliance with Nasdaq'’s continued listing requirements and standards. There can be no assurances that we will be able to comply with the applicable listing requirements and standards of Nasdaq.

Nasdaq requires listed issuers to comply with certain standards in order to remain listed on its exchange. These requirements include, among other things, maintaining a closing bid price for our common stock of $1.00 per share and meeting one of the following three requirements: maintaining at least $2.5 million in stockholders’ equity (the “Minimum Stockholders’ Equity Requirement”); maintaining $35 million of market value of listed securities; or having $500,000 in net income over the prior two years or two of the prior three years. In March 2024, we received notice from the Listing Qualifications staff of Nasdaq (the “Staff”), notifying us that we no longer complied with the Minimum Stockholders' Equity Requirement under Nasdaq Listing Rule 5550(b)(1).

OnIn ~~September~~March 5, 2024, we received notice from the Listing Qualifications staff of Nasdaq ~~notified~~(the “Staff”), notifying us that we ~~had~~no ~~not~~longer ~~regained~~maintained ~~compliance~~at ~~with~~least $2.5 million in stockholders’ equity, as required under Nasdaq Listing Rule 5550(b)(1) (the “Minimum Stockholders’ Equity Requirement”), and ~~that~~also did not meet any other alternative standard. On October 22, 2024, we held our first hearing before a Nasdaq panel, as a result, ~~unless~~of which we ~~timely~~received ~~requested~~additional antime, ~~appeal~~or ofuntil ~~this~~March ~~determination~~4, 2025, to regain compliance.A second hearing was held on July 15, 2025. On July 22, 2025, the panel for our second hearing issued a decision granting our request for continued listing on Nasdaq, ~~Hearings~~subject ~~Panel~~to us demonstrating compliance with (1) the Minimum Stockholders’ Equity Requirement by August 14, 2025; and (2) the Minimum Bid Requirement (as defined below) by September 8, 2025. On August 22, 2025, we received a letter (the “~~Panel~~August 2025 Letter”) from Nasdaq confirming our compliance with Nasdaq Listing Rule 5550(b). Specifically, the August 2025 Letter confirmed that we were in compliance with both (1) Nasdaq ~~would~~Listing ~~move~~Rule to5550(b)(2), ~~suspend~~which ~~trading~~requires a market value of ~~our~~listed ~~common~~securities ~~stock~~of ~~and~~at toleast ~~have~~$35 ~~our~~million ~~shares~~and of(2) ~~common~~the ~~stock~~alternative ~~delisted~~stockholders’ ~~from~~equity ~~The~~threshold under Nasdaq ~~Capital~~Listing ~~Market~~Rule 5550(b)(1), which is the Minimum Stockholders’ Equity Requirement. The ~~Company~~August ~~timely~~2025 ~~requested~~Letter aalso ~~hearing~~provided ~~before~~that, solely with respect to the ~~Panel~~Minimum Stockholders’ Equity Requirement, ~~and~~we ~~the~~remain ~~hearing~~subject ~~was~~to ~~held~~a onone-year ~~October~~panel monitoring period, through August 22, ~~2024~~2026. OnIf, ~~October~~within ~~30,~~that ~~2024~~one-year monitoring period, ~~Nasdaq~~the ~~provided~~Staff usdetermines ~~until~~that ~~March~~we 4,no ~~2025,~~longer tosatisfy ~~notify~~the ~~Nasdaq~~Minimum ~~that~~Stockholders’ Equity Requirement (and we ~~were~~are not then in compliance with one of the alternative standards under Nasdaq Listing Rule 5550(b)), we will not be permitted to provide the Staff with a plan of compliance and the Staff is not permitted to grant additional time to regain compliance with the Minimum Stockholders’ Equity Requirement nor will we be afforded an applicable cure or compliance period. Instead, the Staff will issue a delist determination letter, and we will have an opportunity to request a new hearing before the Nasdaq Hearings Panel, which request would stay any further action by the Staff pending the ultimate outcome of the hearing.

31Minimum Bid Requirement

On May 16, 2025, we received notice from Nasdaq that, because the closing bid price for our common stock had fallen below $1.00 per share for 30 consecutive business days, we no longer complied with the minimum bid price requirement pursuant to Nasdaq Listing Rule 5550(a)(2) (the “Minimum Bid Requirement”). We ~~regained~~were provided an initial compliance period of 180 calendar days, or until November 12, 2025, to regain compliance with the Minimum ~~Stockholders’~~Bid ~~Equity~~ Requirement. inTo ~~connection~~regain ~~with~~compliance, the ~~private~~closing ~~placement~~bid weprice ~~closed~~of onour ~~March~~common 4,stock ~~2025~~must meet or exceed $1.00 ~~For~~per ~~more~~share ~~information~~for ~~regarding~~a ~~the~~minimum ~~private~~of ~~placement,~~10 ~~see~~consecutive ~~“Liquidity~~business ~~and~~days ~~Capital~~prior ~~Resources”~~to ~~below~~November 12, 2025.

~~Pursuant~~On toNovember ~~Nasdaq~~13, ~~Listing Rule 5815(d)(4)(B)~~2025, we ~~will~~received ~~be subject to~~ a ~~Mandatory~~second ~~Panel~~letter ~~Monitor~~from ~~until March 7, 2026. If~~ the Nasdaq Staff ~~finds~~advising ~~we are again out of compliance with the Minimum Stockholders’ Equity Requirement before~~ that ~~date,~~ we ~~will~~had ~~not~~been begranted ~~permitted~~an toadditional ~~provide~~180 ~~the~~calendar ~~Staff~~days, ~~with~~or auntil ~~plan~~May of11, ~~compliance~~2026, ~~with respect~~ to ~~that deficiency and the Staff would not be permitted to grant additional time for us to~~ regain compliance with ~~respect~~the toMinimum ~~that~~Bid ~~deficiency~~Requirement, ~~nor~~in ~~would~~accordance wewith ~~be afforded an applicable cure or compliance period. Instead, the Staff would issue a “Delist Determination Letter” and we would have an opportunity to request a~~ Nasdaq ~~hearing~~Listing ~~panel~~Rule ~~regarding our continued listing~~5810(c)(3)(A).

InWe ~~the~~intend ~~event~~to ~~that~~continue ~~our~~to ~~common~~actively ~~stock~~monitor isthe ~~delisted~~closing ~~from~~bid ~~Nasdaq,~~price asof aour ~~result~~common ofstock ~~our~~and ~~failure~~will evaluate available options to ~~comply~~regain compliance with the Minimum ~~Stockholders’~~Bid ~~Equity~~ Requirement. Specifically, orwe ashave aconfirmed ~~result of our failure~~ to ~~continue~~Nasdaq tothat, ~~comply~~if ~~with any other requirement for continued listing on Nasdaq~~necessary, we ~~may~~will ~~have~~implement toa ~~pursue~~reverse ~~trading~~stock onsplit aof ~~less~~our ~~recognized~~outstanding orcommon ~~accepted~~stock ~~market,~~to ~~such~~attempt asto ~~the~~regain ~~over~~compliance. ~~the~~If ~~counter~~we ~~markets,~~do ~~our~~not ~~stock~~regain ~~may~~compliance bewithin ~~traded~~the asadditional acompliance ~~“penny stock~~period,” ~~which~~Nasdaq ~~would~~will ~~make~~provide ~~transactions~~notice inthat our common stock ~~more~~will ~~difficult~~be ~~and~~subject ~~cumbersome,~~to ~~and~~delisting. weWe ~~may~~would then be ~~unable~~entitled to ~~access~~appeal ~~capital~~that ondetermination ~~favorable~~to ~~terms~~a orNasdaq athearings ~~all,~~panel. asThere ~~companies~~can ~~trading~~be onno ~~alternative~~assurance ~~markets~~that ~~may~~we bewill ~~viewed~~regain ascompliance ~~less attractive investments~~ with ~~higher~~the ~~associated~~Minimum ~~risks,~~Bid ~~such~~Requirement ~~that~~during ~~existing~~the or180-day ~~prospective~~additional ~~institutional~~compliance ~~investors~~period ~~may be less interested in,~~ or ~~prohibited~~maintain ~~from,~~compliance ~~investing~~with ~~in our common stock. This may also cause~~ the ~~market~~other ~~price~~Nasdaq oflisting ~~our common stock to decline~~requirements.

Potential Consequences of Delisting

There is no assurance that we will be able to meet Nasdaq’s listing requirements or comply with the requisite Nasdaq requirements to maintain our listing of common stock on Nasdaq. In the event that our common stock is delisted from Nasdaq, as a result of our failure to comply with the Minimum Stockholders’ Equity Requirement or the Minimum Bid Requirement or as a result of our failure to continue to comply with any other requirement for continued listing on Nasdaq, and we are not able to list our securities on Nasdaq or any other national securities exchange, we could face significant material adverse consequences, including:

•

a decline of the market price of our common stock;

Table of Contents

•

a limited availability of market quotations for our common stock;

•

reduced liquidity for our common stock;

•

a determination that our common stock is a “penny stock,” which will require brokers trading in our common stock to adhere to more stringent rules and possibly result in a reduced level of trading activity in the secondary trading market for our securities;

•

a limited amount of news and analyst coverage for us;

•

a decreased ability to issue additional securities or obtain additional financing in the future; and

•

the incurring of additional costs under state blue sky laws in connection with any sales of our securities.

As of the date of this Annual Report, we require additional funding to develop our product candidates, conduct future operations, and repay our outstanding obligations. If we are unable to obtain the funds necessary to do so because our common stock is not listed on any national securities exchange, we may be required to delay, scale back or eliminate our product development activities, and we may be unable to continue our business operations.

If our common stock is delisted by Nasdaq, our common stock may be eligible to trade on an over-the-counter quotation system where an investor may find it more difficult to sell our stock or obtain accurate quotations as to the market value of our common stock. In the event our common stock is delisted from Nasdaq, we may not be able to list our common stock on another national securities exchange or obtain quotation on an over-the-counter quotation system.

We have had, and we will continue to have, an ongoing need to raise additional cash from outside sources to continue funding our operations, including our continuing substantial research and development expenses and potential commercialization activities. We do not currently believe that our cash balance will be sufficient to fund the development and marketing efforts required to reach profitability without raising additional capital from accessible sources of financing in the near future. Our future capital requirements will depend on many factors, including:

•

our ability to raise capital to fund our operations on terms acceptable to us, or at all;

•

our perceived capital needs with respect to our development programs, and any delays in, adverse events and excessive costs of such programs beyond what we currently anticipate;

•

our ability to establish and maintain collaborative and other arrangements with third parties to assist in bringing our product candidates to market and the cost of such arrangements at the time;

•

costs associated with operating at our Houston, Texas facility;

•

the cost of manufacturing our product candidates, including compliance with good manufacturing practices applicable to our product candidates;

•

expenses related to the establishment of sales and marketing capabilities for product candidates awaiting approval or products that have been approved;

•

competing technological and market developments; and

•

our ability to introduce and sell new products.

The amount and timing of our future funding requirements will depend on many factors, including the pace and results of our clinical development efforts.

We have secured capital historically from grant revenue, collaboration proceeds, and debt and equity offerings. To obtain additional capital, we may pursue debt and/or equity offering programs, strategic corporate partnerships, state and federal development programs, licensing arrangements, and sales of assets or debt or equity securities. We cannot be certain that additional capital will be available on terms acceptable to us, or at all. If we are unsuccessful in our efforts to raise any such additional capital, we may be required to take actions that could materially and adversely harm our business, including a possible significant reduction in our research, development and administrative operations (including reduction of our employee base), the surrender of our rights to some technologies or product opportunities, delay of our clinical trials or regulatory and reimbursement efforts, or curtailment or cessation of operations.

Depending on the type and the terms of any financing we pursue, stockholders’ rights and the value of their investment in our common stock could be reduced. A financing could involve one or more types of securities including common stock, preferred stock, convertible debt or warrants to acquire common stock. These securities could be issued at or below the then prevailing market price for our common stock or with terms or conditions that provide new investors with rights that are superior to those held by our existing stockholders or that have a negative impact on the value of securities held by our existing stockholders. For example, the terms of our recent offerings resulted in substantial dilution to our existing stockholders ~~and significant protections to new investors that are not available to stockholders who invested prior to the offerings~~. In addition, if we issue secured debt securities, the holders of the debt would have a claim to our assets that would be prior to the rights of stockholders until the debt is paid. Interest on these debt securities would increase costs and negatively impact operating results. If the issuance of new securities results in diminished rights to holders of our common stock, the market price of our common stock could be negatively impacted.

3228

Table of Contents

claim to our assets that would be prior to the rights of stockholders until the debt is paid. Interest on these debt securities would increase costs and negatively impact operating results. If the issuance of new securities results in diminished rights to holders of our common stock, the market price of our common stock could be negatively impacted.

We will need to complete additional financing transactions in order to continue operations. These arrangements may also not be sufficient in the near-term. Given, among other things, the current status of the capital markets, our recent stock price performance and the terms of our recent capital financings, there can be no assurances that we will be able to secure additional financing, or if available, that it will be sufficient to meet our needs or be on favorable terms. Additionally, our cost of capital will depend upon numerous factors including, but not limited to, the strength of the financial markets, global market conditions, including inflationary pressures, interest rate fluctuations, our recovery and financial performance, the recovery and performance of our industry in general and the size, scope and timing of our financial needs. If we are unable to access current financings or secure future financings, including for any of the foregoing reasons, it will have a negative impact on our cash flows and our ability to meet our financial obligations. Failure to raise capital as and when needed, on favorable terms or at all, would have a significant negative impact on our financial condition and our ability to develop our product candidates.

Borrowings under our line of credit have the effect of limiting our use of cash and marketable securities.

We have an existing margin loan facility under a line of credit (the “Pershing Credit Facility”) with Pershing LLC (“Pershing”), an affiliate of The Bank of New York Mellon Corporation. The available credit line limit under this facility fluctuates based on our request for extensions from time to time, subject to the value of the collateralized marketable securities we hold with Pershing, provided that the amount available to draw under the facility cannot exceed 91.5% of the value of the collateralized marketable securities deposited with Pershing. Depending on the value of the marketable securities we hold with Pershing, Pershing may require us from time-to-time to deposit additional funds or marketable securities in order to restore the level of collateral to an acceptable level, and the amounts borrowed under the facility are due on demand. Volatility in the global markets could cause the interest rate to fluctuate from time to time increasing our costs, or could cause Pershing to terminate our ability to borrow funds. In addition, borrowings under the Pershing Credit Facility have the effect of limiting our use of cash and marketable securities.

We maintain our cash at financial institutions, often in balances that exceed federally insured limits.

~~Actual~~Our ~~events~~cash ~~involving~~held ~~limited~~in ~~liquidity, defaults,~~ non-~~performance~~interest-bearing or other adverse developments that affect financial institutions, or other companies in the financial services industry or the financial services industry generally, or concerns or rumors about any events of these kinds or other similar risks, have in the past and ~~may in the future lead to market~~interest-~~wide~~bearing ~~liquidity problems. The majority of our cash is held in~~ accounts atexceeds ~~U.S. banking institutions that we believe are of high quality. Cash held in depository accounts may exceed~~ the ~~$250,000~~ Federal Deposit Insurance Corporation (“FDIC”) insurance limits. If such banking institutions were to fail, we could lose all or a portion of those amounts held in excess of such insurance limitations. By way of example, the FDIC took control of Silicon Valley Bank (“SVB”) on March 10, 2023. Similarly, on March 12, 2023, Signature Bank and Silvergate Capital Corp. were each swept into receivership. Although depositors at SVB received access to their funds, uncertainty and liquidity concerns in the broader financial services industry remain. Inflation and rapid increases in interest rates have led to a decline in the trading value of previously issued government securities with interest rates below current market interest rates. The U.S. Department of Treasury, FDIC and Federal Reserve Board have announced a program to provide up to $25 billion of loans to financial institutions secured by such government securities held by financial institutions to mitigate the risk of potential losses on the sale of such instruments. However, widespread demands for customer withdrawals or other needs of financial institutions for immediate liquidity may exceed the capacity of such program. There is no guarantee that the U.S. Department of Treasury, FDIC and Federal Reserve Board will provide access to uninsured funds in the future in the event of the closure of other banks or financial institutions in a timely fashion or at all. Additionally, in the future, our access to our cash in amounts adequate to finance our operations could be significantly impaired by the financial institutions with which we have arrangements directly facing liquidity constraints or failures. Any material loss that we may experience in the future could have a material adverse effect on our financial condition and could materially impact our ability to pay our operational expenses or make other payments.

Our ability to utilize our net operating loss carryforwards and certain other tax attributes may be limited.

We do not expect to make profits in the near future. Under Section 382 of the Internal Revenue Code of 1986, as amended, if a corporation undergoes an “ownership change” (generally defined as a greater than 50% change, by value, in its equity ownership over a three year period), the corporation’s ability to use its pre-change net operating loss carryforwards and other pre-change tax attributes to offset its post-change taxable income and taxes may be limited. We have undergone “ownership changes” as a result of shifts in stock ownership in the past, which significantly limited our ability to use net operating loss carryforwards and other pre-change tax attributes. Any additional ownership change within the definition of Section 382 would further limit our ability to use net operating loss carryforwards and other tax attributes. This change may require us to pay federal income taxes in future years despite generating a loss for federal income tax purposes in prior years.

Risks Related to Our Business and Industry

If we fail to maintain proper and effective internal controls, our ability to produce accurate financial statements on a timely basis could be impaired.

We are subject to the reporting requirements of the Exchange Act, the Sarbanes-Oxley Act and the rules and regulations of Nasdaq. The Sarbanes-Oxley Act requires, among other things, that we maintain effective disclosure controls and procedures and internal control over financial reporting. We must perform system and process evaluation and testing of our internal control over financial reporting to allow management to report on the effectiveness of our internal controls over financial reporting in each Form 10-K, as required by Section 404 of the Sarbanes-Oxley Act.

~~During~~We ~~the~~may ~~quarter ended June 30, 2023, we recognized immaterial grant revenue related to reimbursable development costs incurred~~ in the ~~fourth~~future ~~quarter~~discover ofweaknesses ~~2022 and the first quarter of 2023 that were eligible for revenue recognition~~ in ~~those respective prior periods. These costs were eligible for reimbursement under~~ our ~~CPRIT~~system Grant, but were not correctly recognized in prior period grant revenue due to management’s view that insufficient progress had been made in the ReSPECT-LM clinical trial, despite no performance specific milestones in the grant outside of ainternal ~~reasonableness~~financial ~~test~~and ~~for~~accounting ~~reimbursement~~controls ofand ~~expenses.~~procedures ~~Management has concluded~~ that ~~the~~could ~~correction~~result ~~to grant revenue~~ in ~~the prior periods did not cause~~ a material misstatement of our financial statements. We ~~did~~Our ~~not~~internal ~~have~~control ~~adequate~~over ~~controls~~financial toreporting ~~apply~~will ~~appropriate~~not ~~accounting~~prevent ~~principles~~or todetect ~~significant~~all errors and ~~unusual~~all ~~grant~~fraud. ~~revenue~~A ~~transactions.~~control ~~Specifically~~system, ~~controls~~no ~~over~~matter ~~identification~~how ofwell ~~significant~~designed and~~/or~~ ~~unusual~~operated, ~~transactions~~can ~~requiring~~provide ~~technical~~only ~~analysis~~reasonable, ~~were~~ not ~~operating~~absolute, ~~effectively.~~assurance ~~Management evaluated the impact of this deficiency on our disclosure controls and procedures and concluded~~ that the control ~~deficiency~~system’s ~~represents~~objectives awill ~~material~~be ~~weakness~~met. ABecause ~~material~~of ~~weakness~~the isinherent alimitations ~~deficiency, or a combination of deficiencies,~~ in ~~internal~~all control ~~over financial reporting~~systems, ~~such~~no ~~that~~evaluation ~~there~~of iscontrols acan ~~reasonable~~provide ~~possibility~~absolute assurance that amisstatements ~~material~~due ~~misstatement~~to oferror ~~the~~or ~~Company’s~~fraud ~~annual~~will ornot ~~interim~~occur ~~financial~~or ~~statements~~that ~~will~~all ~~not~~control beissues ~~prevented~~and orinstances ~~detected~~of onfraud awill ~~timely~~be ~~basis~~detected.

In the first quarter of fiscal year 2024, the Company completed the testing of the design and operating effectiveness of the controls over application of appropriate accounting principles to significant and unusual grant revenue transaction. Management has determined that the controls are adequately designed and are operating effectively, and concluded that the material weakness identified in the Quarterly Report on Form 10-Q for the quarter ended June 30, 2023 had been remediated.

We may in the future discover additional weaknesses in our system of internal financial and accounting controls and procedures that could result in a material misstatement of our financial statements. Our internal control over financial reporting will not prevent or detect all errors and all fraud. A control system, no matter how well designed and operated, can provide only reasonable, not absolute, assurance that the control system’s objectives will be met. Because of the inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that misstatements due to error or fraud will not occur or that all control issues and instances of fraud will be detected.

If we are not able to comply with the requirements of Section 404 of the Sarbanes-Oxley Act, or if we are unable to maintain proper and effective internal controls, we may not be able to produce timely and accurate financial statements. If that were to happen, the market price of our common stock could decline and we could be subject to sanctions or investigations by Nasdaq, the SEC or other regulatory authorities.

Furthermore, if ~~our remediation of the material weakness is not effective, or if~~ we experience ~~additional~~ material weaknesses in the future or otherwise fail to maintain an effective system of internal controls in the future, we may not be able to accurately or timely report our financial condition or results of operations, which may adversely affect investor confidence in us and, as a result, the value of our common stock.

Our future success is in large part dependent upon our ability to successfully develop our nanomedicine platform and commercialize ~~REYOBIQ™~~rhenium (186Re) obisbemeda and 188RNL-BAM and any failure to do so could significantly harm our business and prospects.

Our ability to successfully develop and commercialize ~~REYOBIQ™~~rhenium (186Re) obisbemeda and 188RNL-BAM is subject to a number of risks, including the following:

•

we do not have substantive drug development, manufacturing, and commercialization experience, and thus we may be required to hire and rely on significant numbers of scientific, quality, regulatory and other technical personnel with the experience and expertise necessary to develop, manufacture, and commercialize our nanomedicine product candidates. We may be unable to identify, hire and retain personnel with the requisite experience to conduct the operations necessary to obtain regulatory approval and commercialize our RNL product candidates, in which case our business would be materially harmed;

we29 intend to find a commercialization partner to share or assume responsibility for marketing, sales, and distribution activities and related costs and expenses for our RNL product candidates. There can be no assurance that we would obtain sufficient capital to fund the development, manufacturing, and commercialization of our nanomedicine program ourselves,

34Table of Contents

orexpertise ifnecessary weto dodevelop, manufacture, and commercialize our nanomedicine product candidates. We may be unable to identify, hire and retain personnel with the requisite experience to conduct the operations necessary to obtain ~~such~~regulatory ~~capital~~clearance, ~~that~~authorization or approval and commercialize our ~~development,~~RNL ~~manufacturing~~product candidates, ~~and~~in ~~commercialization~~which ~~efforts~~case our business would be ~~successful~~materially harmed; ~~and~~

•

we intend to find a commercialization partner to share or assume responsibility for marketing, sales, and distribution activities and related costs and expenses for our RNL product candidates. There can be no assurance that we would obtain sufficient capital to fund the development, manufacturing, and commercialization of our nanomedicine program ourselves, or if we do obtain such capital, that our development, manufacturing, and commercialization efforts would be successful; and

•

to the extent that we incur unanticipated expenses in our business, are unable to timely obtain sufficient additional capital on terms acceptable to us (or at all) to fund this business, our ability to develop our RNL product candidates could be materially and adversely impacted.

188RNL-BAM will be regulated as a medical device, which may result in additional regulatory and other risks.

188RNL-BAM was developed and tested preclinically as a drug product. The FDA has informed us that 188RNL-BAM will, moving forward, be regulated instead as a medical device.

In the United States, before we can market a new medical device, we must first receive either clearance under Section 510(k) of the FDCA, de novo authorization, or premarket approval (“PMA”), from the FDA, unless an exemption applies. In the process of obtaining either premarket clearance, authorization, or approval, following these routes respectively, the FDA must determine that a proposed device is either substantially equivalent to a legally marketed predicate device with similar intended uses and the same technological characteristics or technological characteristics that do not raise different questions of safety or effectiveness , that a device is either low or moderate risk and its benefits outweigh its risks, or that it is ~~safe~~has a reasonable assurance of safety and ~~effective~~effectiveness for its intended use, based, in part, on extensive data, ~~including~~which may include, but is not limited to, technical, preclinical, clinical, manufacturing and labeling data. The PMA process is typically required for devices that are deemed to pose the greatest risk, such as life sustaining, life supporting or implantable devices.

Modifications to products that are approved through a PMA generally require FDA approval of the modifications through a PMA supplemental application. ~~Both~~The ~~the~~ PMA approval, de novo authorization, and the 510(k) clearance ~~process~~processes can be expensive, lengthy and uncertain. The ~~process~~processes of obtaining a PMA isand a de novo are particularly costly and uncertain and ~~generally~~can ~~takes~~take ~~from~~a ~~one~~year ~~to three years,~~ or even longer, from the time the application is submitted to the FDA. In addition, a PMA and a de novo generally ~~requires~~require the performance of one or more clinical studies. Despite the time, effort and cost, a medical device may not be approved by the FDA. Any delay or failure to obtain necessary regulatory clearance, authorization or approvals could harm our business. Furthermore, even if we are granted regulatory clearance, authorization or approvals, they may include significant limitations on the cleared, authorized, approved and labeled indications for use for the device, which may limit the market for the device.

In addition, comparable foreign regulatory authorities to the FDA have approval policies and regulations related to the safety and performance requirements that apply to 188RNL-BAM, either as medical devices or as drugs, depending on each jurisdiction’s regulatory requirements. Accordingly, to the extent that we intend to sell medical devices or drugs in Member States of the EU or other foreign jurisdictions, the regulatory approval pathway for our product candidates, including 188RNL-BAM, may be uncertain, complex, expensive and lengthy, and approval may not be obtained.

Failure to successfully develop or supply the 188RNL-BAM medical device component, delays in or failure of the studies conducted by us, our collaborators, or third-party providers, or failure of our management, our collaborators, or third-party providers to obtain or maintain regulatory clearance or approval of 188RNL-BAM as a medical device or drug, as applicable in each jurisdiction, could result in increased development costs, delays in or failure to obtain regulatory approval, and associated delays in 188RNL-BAM reaching the market. Further, failure to successfully develop or supply the device, or to gain or maintain its approval, could adversely affect our operations.

We recently acquired the ~~CNSideTM~~CNSide Portfolio, and we may not be successful in our efforts to develop, fully utilize and monetize it.

InSince ~~April~~acquiring ~~2024, we completed~~ the ~~acquisition~~CNSide ofPlatform ~~substantially~~in ~~all of the right~~2024, ~~title~~we ~~and~~have ~~interest~~established ininfrastructure ~~the~~to ~~CNSideTM~~support ~~Platform,~~a ~~including~~scalable ~~the~~and ~~CNSideTM~~centralized ~~Test,~~testing ~~which~~laboratory isin ~~designed to detect~~Houston, ~~quantify,~~TX ~~and~~that ~~monitor~~will ~~tumor~~service ~~status~~the inU.S. LMmarket. We ~~are~~have ~~currently~~been ~~evaluating~~executing ~~and~~on ~~developing~~ our ~~business~~commercial ~~plan~~market ~~for~~access ~~developing~~strategy, ~~the~~which ~~CNSideTM~~includes ~~Portfolio~~prioritized ~~alongside~~state ~~our~~licensure, ~~lead~~proprietary ~~radio~~reimbursement ~~therapeutic candidate~~codes, ~~REYOBIQ™,~~commercial and ~~seeking~~government ~~partnering~~payor coverage, and ~~financing~~value-based ~~opportunities~~pricing ~~for~~to ~~CNSideTM~~optimize revenue. We ~~are planning for the CNSideTM Test to be~~ re-introduced to the ~~U.S.~~CNSide ~~market~~Platform ~~starting~~first in ~~the~~Texas ~~second~~in ~~quarter~~August of 2025~~. However~~, ~~there~~signed ~~can~~national beagreements ~~no assurances that we will be able~~ to ~~develop~~provide the ~~technology~~CNSide toTest ~~allow~~with ~~for~~UnitedHealthcare ~~commercial~~Insurance ~~applications,~~Company orand ~~successfully~~Humana, ~~utilize~~Inc., and ~~fully~~obtained ~~integrate~~state ~~the~~licensure ~~CNSideTM~~for ~~Portfolio~~49 ~~into~~of ~~our~~50 ~~operations.~~US Westates ~~may~~by ~~not~~January ~~generate~~2026, ~~revenues~~with ~~from or realize~~ the ~~anticipated~~remaining ~~benefits~~license offor the ~~CNSideTM~~state ~~Platform~~of ~~within~~New ~~our~~York ~~expected timeline or at all. Contingent~~ on ~~our~~track ~~launch~~for ~~are a number of steps related to certifications, state licensures, payor coverages and reimbursement codes are completed~~2027.

35 On May 6, 2024, the FDA issued a final rule amending the definition of an in vitro diagnostic (“IVD”) device to include tests manufactured by a clinical laboratory. This rule would have required LDTs manufactured by a laboratory to comply with the same general regulatory requirements as other medical devices. Two lawsuits challenging FDA’s authority to regulate LDTs—one by the American

In30 addition, the FDA historically exercised enforcement discretion with respect to LDTs and did not require these tests to be cleared or approved by FDA as long as they complied with CLIA standards. However, on May 6, 2024, the FDA issued a final rule in which it announced it was phasing out its general enforcement discretion approach so that LDTs manufactured by a laboratory will generally fall under the same enforcement approach as other medical devices. According to the final rule this phase out will take place over a period of several years. As a result, CNSide Diagnostics may also be required to comply with these FDA regulations if FDA implements and enforces the final LDT rule, including, among other things, registration and listing, quality system regulations, and premarket authorization. Failure to comply with applicable FDA regulatory requirements may trigger a range of enforcement actions by the FDA, and may disqualify or delay a company from launching an LDT product, or prevent a company with an LDT on the marketing from continuing to sell their test.

Table of Contents

Clinical Laboratory Association and the other by the Association for Molecular Pathology— were filed in federal district courts in Texas in 2024 and were subsequently consolidated.

On March 31, 2025, the court issued an order vacating the final rule, thereby overturning the rulemaking’s associated requirements. The district court ruled that FDA lacks jurisdiction to regulate LDTs because they do not meet the definition of a medical device under the FDC Act. The government did not appeal.

Legislative proposals addressing the FDA’s oversight of LDTs have been previously introduced. For example, the VALID Act, introduced in 2021, 2023 and again in 2025, would have established a new risk-based regulatory framework for in vitro clinical tests (IVCTs), a category which would have included IVDs, LDTs, collection devices and instruments used with such tests. It is unclear whether the court decision will renew interest in a legislative path for LDT regulation.

If the regulatory framework for LDTs changes in the future, CNSide Diagnostics may also be required to comply with these FDA or other, different regulations. Failure to comply with applicable regulatory requirements may trigger a range of enforcement actions, and may disqualify or delay a company from launching an LDT product, or prevent a company with an LDT on the marketing from continuing to sell their test.

There can be no assurance that we will be able to generate or grow sales of the CNSide Test or that we will develop or commercialize any other diagnostic products or services that will generate significant revenue. The commercial success of our tests, our successful commercialization of any new diagnostic products and our ability to generate revenues will depend on a variety of factors, including the following:

•

acceptance in the medical community;

•

inclusion in healthcare guidelines and recommendations;

•

inclusion in quality measures;

•

recommendations and studies that may be published by government agencies, professional organizations, academic or medical journals or other key opinion leaders;

•

patient acceptance and demand;

•

patient compliance with orders for our tests by healthcare providers, and patient adherence to recommendations regarding periodic re-testing;

•

effective marketing and educational programs, including successful direct-to-patient marketing such as television advertising and social media;

•

sufficient coverage and reimbursement by payers;

•

the existence of federal or state laws that mandate coverage for CNS cancers and other types of screening, the extent to which those laws mandate coverage of our tests and the enforcement of those laws;

•

the amount and nature of competition from other products and procedures;

•

maintaining regulatory licensure, clearance, authorization, or approvals to legally market our products and services; and

•

the ease of use of our ordering process for healthcare providers.

If we are unable to generate or grow sales of the CNSide Test, we are delayed or limited in doing so, or we are unable to successfully commercialize the CNSide Test, our business prospects, financial condition, and results of operations would be adversely affected.

If we are unable to successfully partner with other companies to commercialize our product candidates, our business could materially suffer.

A key part of our business strategy is to leverage strategic partnerships and collaborations to commercialize our product candidates. We do not have the financial, human or other resources necessary to develop, commercialize, launch or sell our therapeutic offerings in all of the geographies that we are targeting, and thus it is important that we identify and partner with third parties who possess the necessary resources to bring our product candidates to market. We expect that any such partners will provide regulatory and reimbursement/pricing expertise, sales and marketing resources, and other expertise and resources vital to the success of our product offerings in their territories. We further expect, but cannot guarantee, that any such partnering arrangements will include upfront cash payments to us in return for the rights to develop, manufacture, and/or sell our product candidates in specified territories, as well as downstream revenue in the form of milestone payments and royalties. If we are unable to successfully partner with other companies to commercialize our product candidates, our business could materially suffer.

~~Our~~31 success depends in substantial part on our ability to obtain regulatory approvals for our RNL product candidates. However, we cannot be certain that we will receive regulatory approval for these product candidates or our other product candidates.

WeTable ~~have a limited number~~ of product candidates in development, and our business depends substantially on their successful development and commercialization. Our product candidates will require development, regulatory review and approval in multiple jurisdictions, substantial investment, access to sufficient commercial manufacturing capacity and significant marketing efforts before we can generate any revenue from sales of our product candidates. The research, testing, manufacturing, labeling, approval, sale, marketing and distribution of products are subject to extensive regulation by the FDA and other regulatory authorities in the United States and other countries, whose regulations differ from country to country.Contents

WeOur ~~are~~success ~~not~~depends ~~permitted to market our product candidates~~ in ~~the~~substantial ~~United~~part ~~States~~on ~~until~~our weability ~~receive~~to ~~approval~~obtain ~~from the FDA~~regulatory clearance, authorization or ~~in any foreign countries until we receive the requisite~~ approval ~~from~~for ~~the~~our ~~regulatory~~RNL ~~authorities~~product ofcandidates. However, ~~such~~we ~~countries~~cannot ~~(including~~be ~~centralized~~certain ~~marketing~~that ~~authorization from the European Commission), and~~ we ~~may~~will ~~never~~ receive ~~such~~ regulatory ~~approvals.~~clearance, ~~Obtaining~~authorization ~~regulatory~~or approval for athese product ~~candidate is a lengthy, expensive and uncertain process, and may not be obtained. Any failure to obtain regulatory approval of any of our product~~ candidates ~~would~~or ~~limit~~ our ~~ability~~other to generate future revenue (and any failure to obtain such approval for all of the indications and labeling claims we deem desirable could reduce our potential revenue), would potentially harm the development prospects of our product candidates ~~and would have a material and adverse impact on our business~~.

~~Even~~We ifhave wea ~~successfully~~limited ~~obtain~~number ~~regulatory~~of ~~approvals~~product tocandidates ~~market~~in development, and our business depends substantially on their successful development and commercialization. Our product candidates, ~~our~~will ~~revenue~~require ~~will~~development, beregulatory ~~dependent~~review and clearance, authorization or approval in ~~part~~multiple jurisdictions, onsubstantial ~~our~~investment, ~~ability~~access to ~~commercialize~~sufficient ~~such~~commercial ~~products~~manufacturing ascapacity ~~well~~and assignificant ~~the~~marketing ~~size~~efforts ofbefore ~~the~~we ~~markets~~can ingenerate ~~the~~any ~~territories~~revenue ~~for~~from ~~which~~sales weof ~~gain~~our ~~regulatory~~product ~~approval~~candidates. IfThe ~~the~~research, ~~markets~~testing, ~~for~~manufacturing, ~~our~~labeling, ~~product~~approval, ~~candidates~~sale, marketing and distribution of products are ~~not~~subject asto ~~significant~~extensive asregulation weby ~~estimate,~~the ~~our~~FDA ~~business~~and other regulatory authorities in the United States and ~~prospects~~other ~~will~~countries, bewhose ~~harmed~~regulations differ from country to country.

IfWe aare ~~product~~not ~~candidate~~permitted isto ~~not~~market ~~approved~~our product candidates in athe ~~timely~~United ~~fashion~~States onuntil ~~commercially~~we ~~viable~~receive ~~terms~~clearance, authorization or ifapproval ~~development~~from ofthe FDA, or in any ~~product~~foreign ~~candidate~~countries isuntil ~~terminated~~we ~~due~~receive tothe ~~difficulties~~requisite orclearance, ~~delays~~authorization ~~encountered~~or inapproval from the regulatory ~~approval~~authorities ~~process,~~of itsuch ~~could~~countries ~~have~~(including acentralized ~~material~~marketing ~~adverse~~authorization ~~effect~~from onthe ~~our~~European ~~business~~Commission), and we may ~~become~~never ~~more~~receive ~~dependent~~such onregulatory ~~the~~clearance, ~~development~~authorization ofor ~~other~~approvals. ~~proprietary~~Obtaining ~~products~~regulatory ~~and/~~clearance, authorization or ~~our~~approval ~~ability~~for toa ~~successfully~~product ~~acquire~~candidate ~~other~~is ~~products~~a lengthy, expensive and ~~technologies.~~uncertain ~~There~~process, ~~can~~and may not be noobtained. ~~assurance~~Any ~~that~~failure to obtain regulatory clearance, authorization or approval of any of our product ~~candidate~~candidates ~~will~~would ~~receive~~limit ~~regulatory~~our ~~approval~~ability into agenerate ~~timely~~future ~~manner~~revenue (and any failure to obtain such clearance, authorization or atapproval for all. of the indications and labeling claims we deem desirable could reduce our potential revenue), would potentially harm the development prospects of our product candidates and would have a material and adverse impact on our business.

Even if we successfully obtain regulatory clearance, authorization or approvals to market our product candidates, our revenue will be dependent, in part, on our ability to commercialize such products as well as the size of the markets in the territories for which we gain regulatory clearance, authorization or approval. If the markets for our product candidates are not as significant as we estimate, our business and prospects will be harmed.

If a product candidate is not cleared, authorized or approved in a timely fashion on commercially viable terms, or if development of any product candidate is terminated due to difficulties or delays encountered in the regulatory clearance, authorization or approval process, it could have a material adverse effect on our business, and we may become more dependent on the development of other proprietary products and/or our ability to successfully acquire other products and technologies. There can be no assurance that any product candidate will receive regulatory approval in a timely manner, or at all.

We are currently party to certain licensing, collaboration and acquisition agreements under which we may make or receive future payments in the form of milestone payments, maintenance fees, royalties and/or minimum product purchases. Our collaborators may not devote the attention and resources to such efforts to be successful. The termination of a key collaboration agreement by one of our collaborators could materially impact our ability to enter into additional collaboration agreements with new collaborators on favorable terms.

36On March 29, 2020, we entered into an exclusive license agreement with NanoTx for the global rights to develop and commercialize NanoTx’s glioblastoma treatment, rhenium (186Re) obisbemeda. Under the license agreement with NanoTx, we are required to use commercial reasonable efforts to develop the rhenium (186Re) obisbemeda product candidate acquired under the license agreement. Further, we are subject to future milestone, earn-out and other payments to NanoTx all of which are tied to our commercialization and sale activities for product candidates. If we are unsuccessful in our efforts to develop these assets, or if NanoTx and we were to enter into a dispute over the terms of our agreement, then our business could be seriously harmed.

On March 29, 2020, we entered into an exclusive license agreement with NanoTx for the global rights to develop and commercialize NanoTx’s glioblastoma treatment, REYOBIQ™. Under the license agreement with NanoTx, we are required to use commercial reasonable efforts to develop the REYOBIQ™ product candidate acquired under the license agreement. Further, we are subject to future milestone, earn-out and other payments to NanoTx all of which are tied to our commercialization and sale activities for product candidates. If we are unsuccessful in our efforts to develop these assets, or if NanoTx and we were to enter into a dispute over the terms of our agreement, then our business could be seriously harmed.

On December 31, 2021, we entered into an exclusive license agreement with UTHSCSA for the global rights to develop and commercialize Rhenium-188 NanoLiposome biodegradable alginate microspheres (188RNL-BAM). Under the license agreement with UTHSCSA, we are required to use commercial reasonable efforts to develop the 188RNL-BAM product candidate acquired under the license agreement. Further, we are subject to future milestone, earn-out and other payments to UTHSCSA all of which are tied to our commercialization and sale activities for product candidates. If we are unsuccessful in our efforts to develop these assets, or if UTHSCSA and we were to enter into a dispute over the terms of our agreement, then our business could be seriously harmed.

If we breach any of the agreements under which we license the use, development and commercialization rights to our product candidates or technology from third parties, we could lose license rights that are important to our business. Licensing of intellectual property is of critical importance to our business and involves complex legal, business and scientific issues. Disputes may arise between us and our licensors regarding intellectual property subject to a license agreement, including:

•

the scope of rights granted under the license agreement and other interpretation-related issues;

•

whether and the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement;

Table of Contents

•

our right to sublicense patents and other intellectual property rights to third parties under collaborative development relationships;

•

our diligence obligations with respect to the use of the licensed technology in relation to our development and commercialization of our product candidates, and what activities satisfy those diligence obligations;

•

the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners; and

•

whether and the extent to which inventors are able to contest the assignment of their rights to our licensors.

If disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on acceptable terms or at all, we may be unable to successfully develop and commercialize the affected product candidates. In addition, if disputes arise as to ownership of licensed intellectual property, our ability to pursue or enforce the licensed patent rights may be jeopardized. If we or our licensors fail to adequately protect this intellectual property, our ability to commercialize our products could suffer.

Our current business strategy is high-risk and may not be successful.

Our current business strategy is to aggressively develop our nanomedicine platforms and CNSide™ Platform, while simultaneously controlling expenses, which is a high-risk strategy for a number of reasons including the following:

•

we do not have prior experience with obtaining regulatory, reimbursement, or other approvals for product candidates such as ~~REYOBIQ™~~rhenium (186Re) obisbemeda and 188RNL-BAM or the CNSide™ Test;

•

our nanomedicine product candidates, if commercialized, will compete against established competitive drugs that are marketed and sold by large companies with significant human, technical and financial resources;

•

we are not experienced in acquiring and integrating new assets;

•

there is an intense and rapidly evolving competitive landscape for our nanomedicine product candidates, including chemotherapies, targeted therapies and immuno-oncology therapies, and as such key assumptions regarding market entry, pricing, and revenue/unit share may not be realized;

•

our product candidates and clinical laboratory tests may never become commercially viable; and

•

we may not be able to prevent other companies from depriving us of market share and profit margins by selling products based on our intellectual property and developments.

A significant portion of our funding will come from grants received from CPRIT. The CPRIT Grant includes provisions that reflect the government’s substantial rights and remedies, many of which are not typically found in commercial contracts, including powers of the government to potentially require repayment of all or a portion of the grant award proceeds, in certain cases with interest, in the event we violate certain covenants pertaining to various matters that include any potential relocation outside of the State of Texas. After the CPRIT Grant ends, we are not permitted to retain any unused grant award proceeds without CPRIT’s approval, but our obligation to pay CPRIT sales-based royalty, if and when commercialization is achieved, and other obligations, including our obligation to repay the disbursed grant proceeds under certain circumstances, to maintain certain records and documentation, to notify CPRIT of certain unexpected adverse events and our obligation to use reasonable efforts to ensure that any new or expanded preclinical testing, clinical trials, commercialization or manufacturing related to any aspect to our CPRIT project take place in Texas, survive the termination of the agreement.

in the event we violate certain covenants pertaining to various matters that include any potential relocation outside of the State of Texas. After the CPRIT Grant ends, we are not permitted to retain any unused grant award proceeds without CPRIT’s approval, but our obligation to pay CPRIT sales-based royalty, if and when commercialization is achieved, and other obligations, including our obligation to repay the disbursed grant proceeds under certain circumstances, to maintain certain records and documentation, to notify CPRIT of certain unexpected adverse events and our obligation to use reasonable efforts to ensure that any new or expanded preclinical testing, clinical trials, commercialization or manufacturing related to any aspect to our CPRIT project take place in Texas, survive the termination of the agreement.

Our award from CPRIT requires us to pay CPRIT a portion of our revenues from sales of certain products by us, or received from our licensees or sublicensees, at tiered percentages of revenue in the low- to mid-single digits until the aggregate amount of such payments equals 400% of the grant award proceeds, and thereafter at a rate of 0.5% for as long as we maintain government exclusivity, subject to our right, under certain circumstances, to make a one-time payment in a specified amount to CPRIT to terminate such payment obligations. In addition, the grant contract also contains a provision that provides for repayment to CPRIT of some amount not to exceed the full amount of the grant proceeds under certain specified circumstances involving relocation of our principal place of business outside Texas.

The CPRIT Grant requires us, as a Texas-based company, to meet certain criteria, including among other things, that we maintain our headquarters in Texas and use certain vendors, consultants and employees that are located in Texas. If we fail to maintain compliance with any such requirements that may apply to us now or in the future, we may be subject to potential liability and to termination of our contracts, and potentially full repayment of the CPRIT Grant.

The DoD Award is dependent on continued U.S. government funding and government appropriations, which may not be forthcoming on a timely basis or at all.

The DoD Award, which entitles us to receive a $3.0 million fund for research and development purposes over a three-year period, and any future U.S. federal government grants we may receive, are dependent on government funding, which is generally subject to Congressional appropriations or continued government operations. Such grants are dependent upon sufficient funding for, and timely payment by, the entities providing any such grants. If the granting governmental agency does not receive sufficient appropriations for any reason, including due to a government shutdown or changes in the prevailing policies and budgetary priorities of the incumbent administration, it may terminate our grant (in whole or in part) or reduce the scope of our grant, or delay or reduce payment to us. Any inability to award us any part of the DoD Award, any delay in payment, or the termination of the DoD Award, in whole or in part, due to a lapse in funding or otherwise, could adversely affect our business, financial condition or results of operations, or cash flows. The nature and timing of any related developments remain uncertain.

Table of Contents

administration, it may terminate our grant (in whole or in part) or reduce the scope of our grant, or delay or reduce payment to us. Any inability to award us any part of the DoD Award, any delay in payment, or the termination of the DoD Award, in whole or in part, due to a lapse in funding or otherwise, could adversely affect our business, financial condition or results of operations, or cash flows. The nature and timing of any related developments remain uncertain.

The life science industry is characterized by rapidly advancing technologies, intense competition, and a strong emphasis on proprietary therapeutics. We face competition from a number of sources, some of which may target the same indications as our products or product candidates, including small and large, domestic and multinational, medical device, biotechnology and pharmaceutical companies, academic institutions, government agencies, and private and public research institutions.

Competitors may have greater experience in developing drugs and clinical laboratory tests, conducting clinical trials, obtaining regulatory clearances or approvals, manufacturing and commercialization. It is possible that competitors may obtain patent protection, approval, authorization, or clearance from the FDA or achieve commercialization earlier than we can, any of which could have a substantial negative effect on our business. Many of our potential competitors have substantially greater:

•

capital resources;

•

research and development resources and experience, including personnel and experience;

•

product development, clinical trial and regulatory resources and experience;

•

sales and marketing resources and experience;

•

manufacturing and distribution resources and experience;

•

name, brand and product recognition; and

•

resources, experience and expertise in prosecution and enforcement of intellectual property rights.

We expect the product candidates in our pipeline, if approved, to compete on the basis of, among other things, product efficacy and safety, time to market, price, coverage, and reimbursement by third-party payers, extent of adverse side effects, and convenience of treatment procedures. One or more of our competitors may develop other products that compete with ours, obtain necessary clearance, authorization, or approvals for such products from the FDA, the European Commission, Ministry of Health, Labour and Welfare or other agencies, if required, more rapidly than we do or develop alternative products or therapies that are safer, more effective and/or more cost effective than any products developed by us. The competition that we encounter with respect to any of our product candidates that receive the requisite regulatory clearance, authorization, or approval and classification and are marketed may have an effect on our product prices, market share, and results of operations. We may not be able to differentiate any products that we are able to market from those of our competitors, successfully develop or introduce new products that are less costly or offer better results than those of our competitors, or offer purchasers of our products payment and other commercial terms as favorable as those offered by our competitors.

38As a result of these factors, our competitors may obtain regulatory clearance, authorization, or approval of their products more quickly than we are able to or may obtain patent protection or other intellectual property rights, including regulatory exclusivities, that limit or block us from developing or commercializing our product candidates. Our competitors may also develop products that are more effective, more useful, better tolerated, subject to fewer or less severe side effects, more widely prescribed or accepted, or less costly than ours and may also be more successful than we are in manufacturing and marketing their products. If we are unable to compete effectively with the marketed therapeutics of our competitors or if such competitors are successful in developing products that compete with any of our product candidates that are cleared, authorized, or approved, our business, results of operations, financial condition, and prospects may be materially adversely affected.

rapidly than we do or develop alternative products or therapies that are safer, more effective and/or more cost effective than any products developed by us. The competition that we encounter with respect to any of our product candidates that receive the requisite regulatory approval and classification and are marketed may have an effect on our product prices, market share, and results of operations. We may not be able to differentiate any products that we are able to market from those of our competitors, successfully develop or introduce new products that are less costly or offer better results than those of our competitors, or offer purchasers of our products payment and other commercial terms as favorable as those offered by our competitors.

As a result of these factors, our competitors may obtain regulatory approval of their products more quickly than we are able to or may obtain patent protection or other intellectual property rights that limit or block us from developing or commercializing our product candidates. Our competitors may also develop products that are more effective, more useful, better tolerated, subject to fewer or less severe side effects, more widely prescribed or accepted, or less costly than ours and may also be more successful than we are in manufacturing and marketing their products. If we are unable to compete effectively with the marketed therapeutics of our competitors or if such competitors are successful in developing products that compete with any of our product candidates that are approved, our business, results of operations, financial condition, and prospects may be materially adversely affected.

Clinical testing of our product candidates is a long, expensive and uncertain process, and the failure or delay of a clinical trial can occur at any stage. Many factors, currently known and unknown, can adversely affect clinical trials and the ability to evaluate a product candidate’s efficacy. During the course of treatment, patients can die or suffer other adverse events for reasons that may or may not be related to the proposed product being tested. Even if initial results of preclinical and nonclinical studies or clinical trial results are promising, we may obtain different results in subsequent trials or studies that fail to show the desired levels of safety and efficacy, or we may not obtain applicable regulatory approval for a variety of other reasons.

Further, with respect to the conduct and results of clinical trials generally, in the United States, Europe, Japan, and other jurisdictions, the conduct and results of clinical trials can be delayed, limited, suspended, or otherwise adversely affected for many reasons, including, among others:

•

delay or failure in reaching agreement with the FDA or other regulatory authorities outside of the United States on acceptable clinical trial design, or in obtaining authorization to commence a trial;

Table of Contents

•

delay or failure in reaching agreement on acceptable terms with prospective clinical research organizations (“CROs”), and clinical trial sites;

•

delay or failure in obtaining approval of an IRB or ethics committees before a clinical trial can be initiated at a prospective trial site;

•

withdrawal of clinical trial sites from our clinical trials, including as a result of changing standards of care or the ineligibility of a site to participate;

•

clinical results may not meet prescribed endpoints for the studies, produce negative or inconclusive results, or otherwise not provide sufficient data to support the efficacy of our product candidates;

•

clinical and nonclinical test results may reveal side effects, adverse events or unexpected safety issues associated with the use of our product candidates;

•

~~emerging~~emergence of dosing issues;

•

lack of adequate funding to continue the clinical trials, including the incurrence of unforeseen costs due to enrollment delays, requirements to conduct additional trials and studies, and increased expenses associated with the services of our CROs and other third parties;

•

inability to design appropriate clinical trial protocols;

•

slower than expected rates of subject recruitment and enrollment rates in clinical trials;

•

clinical sites or investigators may deviate from trial protocol or fail to conduct the trial in accordance with applicable regulatory requirements, or drop out of a trial;

•

regulatory review may not find a product safe or effective enough to merit either continued testing or final approval;

•

regulatory authorities may require that we change our studies or conduct additional studies which may significantly delay or make continued pursuit of approval commercially unattractive;

•

a regulatory agency may reject our trial data or disagree with our interpretations of either clinical trial data or applicable regulations;

•

the cost of clinical trials required for product approval may be greater than what we originally anticipate, and we may decide to not pursue regulatory approval for such a product;

•

changes in the standard of care of the indication being studied;

•

a regulatory agency may identify problems or other deficiencies in our existing manufacturing processes or facilities or the existing processes or facilities of our collaborators, our contract manufacturers, or our raw material suppliers;

•

a regulatory agency may change its formal or informal approval requirements and policies, act contrary to previous guidance, adopt new regulations, or raise new issues or concerns late in the approval process; and

•

a regulatory agency may put a clinical study on hold pending additional safety data (and there can be no assurance that we will be able to satisfy the regulator agencies’ requests in a timely manner, which can lead to significant uncertainty in the completion of a clinical study).

We also face clinical trial-related risks with regard to our reliance on other third parties in the performance of many of the clinical trial functions, including CROs that help execute our clinical trials, the hospitals and clinics at which our trials are conducted, the clinical investigators at the trial sites, and other third-party service providers. Failure of any third-party service provider to adhere to applicable trial protocols, laws and regulations in the conduct of one of our clinical trials could adversely affect the conduct and results of such trial (including possible data integrity issues), which could seriously harm our business.

We, the FDA, other regulatory authorities outside the United States, or an IRB may suspend a clinical trial at any time for various reasons, including if it appears that the clinical trial is exposing participants to unacceptable health risks or if the FDA or one or more other regulatory authorities outside the United States find deficiencies in our IND or similar application outside the United States or the conduct of the trial. If we experience delays in the completion of, or the termination of, any clinical trial of any of our product candidates, the commercial prospects of such product candidate will be harmed, and our ability to generate product revenues from such product candidate will be delayed or inhibited. In addition, any delays in completing our clinical trials will increase our costs, slow down our product candidate development and approval process, and jeopardize our ability to commence product sales and generate revenues. Any of these occurrences may harm our business, financial condition, results of operations, cash flows and prospects significantly. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates. Further, regulatory authorities may disagree with our clinical trial design and our interpretation of data from clinical trials, or may change the requirements for approval even after they have reviewed and commented on the design for our clinical trials.

The development of our product candidates also may be delayed by other events beyond our control. For example, actions to limit federal agency budgets or personnel, may result in reductions to the FDA’s budget, employees, and operations, as well as changes to FDA regulatory programs, all of which may lead to slower response times and longer review periods, potentially affecting our ability to progress development of our product candidates, undergo regulatory inspections or obtain regulatory approval for our product candidates.

~~Pre-clinical~~Preclinical studies and preliminary and interim data from clinical trials of our product candidates are not necessarily predictive of the results or success of ongoing or future clinical trials of our product candidates.

~~Pre-clinical~~35 studies and any positive preliminary and interim data from our clinical trials of our product candidates may not necessarily be predictive of the results of ongoing or later clinical trials. A number of companies in the pharmaceutical and biotechnology industries, including us and many other companies with greater resources and experience than us, have suffered significant setbacks in clinical trials, even after seeing promising results in prior pre-clinical studies and clinical trials. Preclinical studies and Phase 1 clinical trials are primarily designed and operate to test safety, to study pharmacokinetics and pharmacodynamics and to understand the side effects of product candidates at various doses and schedules. Even if we are able to complete our planned clinical trials of our product candidates according to our current development timeline, initial positive results from pre-clinical studies and early clinical trials of our product candidates may not be replicated in subsequent clinical trials. The design of our later stage clinical trials could differ in significant ways (e.g., inclusion and exclusion criteria, endpoints, statistical analysis plan) from our earlier stage clinical trials, which could cause the outcomes of the later stage trials to differ from those of our earlier stage clinical trials. If we fail to produce positive results in our planned clinical trials of any of our product candidates, the development timeline and regulatory approval and commercialization prospects for our product candidates, and, correspondingly, our business and financial prospects, could be materially adversely affected. If we fail to produce positive results in our planned clinical trials of any of our product candidates, the development timeline and regulatory approval and commercialization prospects for such product candidates, and, correspondingly, our business and financial prospects, could be materially adversely affected.

Table of Contents

Preclinical studies and any positive preliminary and interim data from our clinical trials of our product candidates may not necessarily be predictive of the results of ongoing or later clinical trials. A number of companies in the pharmaceutical and biotechnology industries, including us and many other companies with greater resources and experience than us, have suffered significant setbacks in clinical trials, even after seeing promising results in prior preclinical studies and clinical trials. Preclinical studies and Phase 1 clinical trials are primarily designed and operate to test safety, to study pharmacokinetics and pharmacodynamics and to understand the side effects of product candidates at various doses and schedules. Even if we are able to complete our planned clinical trials of our product candidates according to our current development timeline, initial positive results from preclinical studies and early clinical trials of our product candidates may not be replicated in subsequent clinical trials. The design of our later stage clinical trials could differ in significant ways (e.g., inclusion and exclusion criteria, endpoints, statistical analysis plan) from our earlier stage clinical trials, which could cause the outcomes of the later stage trials to differ from those of our earlier stage clinical trials. If we fail to produce positive results in our planned clinical trials of any of our product candidates, the development timeline and regulatory approval and commercialization prospects for our product candidates, and, correspondingly, our business and financial prospects, could be materially adversely affected. If we fail to produce positive results in our planned clinical trials of any of our product candidates, the development timeline and regulatory approval and commercialization prospects for such product candidates, and, correspondingly, our business and financial prospects, could be materially adversely affected.

We are an early-stage company with limited resources and revenues. The product candidates we currently have under development will require significant development, ~~pre-clinical~~preclinical and clinical testing and investment of significant funds before their commercialization. Because of this, we must make strategic decisions regarding resource allocations and which product candidates to pursue. There can be no assurance that we will be able to develop all potentially promising product candidates that we may identify. Based on preliminary results, we may choose to advance a particular product candidate that later fails to be successful, and simultaneously forgo or defer further investment in other product candidates that later are discovered to demonstrate greater promise in terms of clinical and commercial success. If we make resource allocation decisions that later are shown to be inaccurate, our business and prospects could be harmed.

terms of clinical and commercial success. If we make resource allocation decisions that later are shown to be inaccurate, our business and prospects could be harmed.

Clinical trial results may fail to support approval of our product candidates.

Even if our clinical trials are successfully completed as planned, the results may not support approval of our product candidates under the laws and regulations of the FDA or other regulatory authorities outside the United States. The clinical trial process may fail to demonstrate that our product candidates are both safe and/or effective for their intended uses. ~~Pre-clinical~~Preclinical and clinical data and analyses are often able to be interpreted in different ways. Even if we view our results favorably, if a regulatory authority has a different view, we may still fail to obtain regulatory approval of our product candidates. The FDA may also require us to conduct additional preclinical studies or clinical trials for our product candidates either prior to or post-approval, or it may object to elements of our clinical development program, requiring their alteration. This, in turn, would significantly adversely affect our business prospects.

We rely on third parties in the performance of many of the clinical trial functions, including CROs, which help execute our clinical trials, the hospitals and clinics at which our trials are conducted, the clinical investigators at the trial sites, and other third-party service providers. Failure of any third-party service provider to adhere to applicable trial protocols, GCP, laws and regulations in the conduct of one of our clinical trials could adversely affect the conduct and results of such trial (including possible data integrity issues), which could seriously harm our business. As a result, results from our clinical trials may be delayed, which in turn would have a material adverse impact on our clinical trial plans and timelines and impair our ability to successfully complete clinical development, obtain regulatory approval, or commercialize our product candidates. This in turn would substantially harm our business and operations.

We also rely on third-party contract manufacturing organizations (“CMOs”) for all our requirements for raw materials, drug substance, and drug product. We have entered into contracts with third-party manufacturers to manufacture, supply, store and distribute supplies of our product candidates for our clinical trials. If any of our product candidates receives FDA approval, we expect to rely on third-party contractors to manufacture our drugs. We have no current plans to build internal manufacturing capacity for any product candidate, and we have no long-term supply arrangements with our current CMOs.

Our reliance on third-party manufacturers exposes us to potential risks, such as the following:

•

we may be unable to contract with third-party manufacturers on acceptable terms, or at all, because the number of potential manufacturers is limited. Potential manufacturers of any product candidate that is approved will be subject to FDA compliance inspections and any new manufacturer would have to be qualified to produce our products;

•

our third-party manufacturers might be unable to formulate and manufacture our drugs in the volume and of the quality required to meet our clinical and commercial needs, if any;

•

our third-party manufacturers may not perform as agreed or may not remain in the contract manufacturing business for the time required to supply our clinical trials through completion or to successfully produce, store and distribute our commercial products, if approved;

Table of Contents

•

changes to our CMOs during clinical trials or after approval may require us to conduct additional studies to demonstrate comparability between the products;

•

drug manufacturers are subject to ongoing periodic unannounced inspection by the FDA and other government agencies to ensure compliance with cGMP and other government regulations and corresponding foreign standards. We do not have control over third-party manufacturers’ compliance with these regulations and standards, but we ~~may~~are ~~ultimately be~~ responsible for ensuring compliance with these requirements, and any offailure ~~their~~to ~~failures~~maintain compliance with applicable regulatory standards by our third-party manufacturers could delay or harm our ability to obtain approval for our products;

•

if any third-party manufacturer makes improvements in the manufacturing process for our products, we may not own, or may have to share, the intellectual property rights to such improvements; and

•

a third-party manufacturer may gain knowledge from working with us that could be used to supply one of our competitors with a product that competes with ours.

Each of these risks could delay or have other adverse impacts on our clinical trials and the approval and commercialization of our product candidates, potentially resulting in higher costs, reduced revenues or both.

We may have difficulty enrolling, or fail to enroll patients, in our clinical trials, which could delay or prevent clinical trials of our drug candidates.

Identifying and enrolling patients to participate in clinical trials of our product candidates is essential to our success. The timing of our clinical trials depends in part on the rate at which we can recruit patients to participate in clinical trials of our product candidates, and we may experience delays in our clinical trials if we encounter difficulties in enrollment. The eligibility criteria of our planned clinical trials may further limit the available eligible trial participants as we require that patients have specific characteristics that we can measure or meet the criteria to assure their conditions are appropriate for inclusion in our clinical trials. We may not be able to identify, recruit and enroll a sufficient number of patients to complete our clinical trials in a timely manner because of the perceived risks and benefits of the drug candidate under study, the availability and efficacy of competing therapies and clinical trials, and the willingness of physicians to participate in our planned clinical trials. If patients are unwilling to participate in our clinical trials for any reason, the timeline for conducting trials and obtaining regulatory approval of our drug candidates may be delayed.

risks and benefits of the drug candidate under study, the availability and efficacy of competing therapies and clinical trials, and the willingness of physicians to participate in our planned clinical trials. If patients are unwilling to participate in our clinical trials for any reason, the timeline for conducting trials and obtaining regulatory approval of our drug candidates may be delayed.

If we experience delays in the completion of, or termination of, any clinical trials of our drug candidates, the commercial prospects of our product candidates could be harmed, and our ability to generate product revenue from any of these product candidates could be delayed or prevented. In addition, any delays in completing our clinical trials would likely increase our overall costs, impair product candidate development and jeopardize our ability to obtain regulatory approval relative to our current plans. Any of these occurrences may materially and adversely harm our business, financial condition, and prospects.

If a particular product candidate causes significant adverse events, then we may be unable to receive regulatory approval or market acceptance for such product candidate.

We may experience numerous unforeseen events during, or as a result of, the testing process that could delay or prevent commercialization of any of our product candidates, including the occurrence of significant adverse events in clinical trials. Such significant adverse events could lead to clinical trial challenges, such as difficulties in patient recruitment, retention, and adherence, potential product liability claims, and possible trial termination by us, regulatory authorities, and/or an IRB or ethics committees. These types of clinical trial challenges could delay or prevent regulatory approval of our product candidate. Significant adverse events may also lead regulatory authorities to require additional warnings on the label for such product, require us to conduct additional costly post-marketing studies, require us to develop a REMS, among other possible requirements. If the product candidate has already been approved, such approval may be withdrawn. Any delay in, denial, or withdrawal of marketing approval for one of our product candidates will adversely affect our financial position. Even if our product candidates receive marketing approval, undesirable side effects may limit the product’s commercial viability. Patients may not wish to use our product, physicians may not prescribe our product, and our reputation may suffer. Any of these events may significantly harm our business and financial prospects.

If our product candidates and technologies receive regulatory approval but do not achieve broad market acceptance, especially by physicians, the revenue that we generate will be limited.

The commercial success of any of our approved products or technologies will depend upon the acceptance of these products and technologies by physicians, patients and the medical community. The degree of market acceptance of these products and technologies will depend on a number of factors, including, among others:

•

acceptance by physicians and patients of the product as a safe and effective treatment;

•

any negative publicity or political action related to our or our competitors’ products or technologies;

•

the relative convenience and ease of administration;

•

the prevalence and severity of adverse side effects;

•

demonstration to authorities of the pharmacoeconomic benefits;

•

demonstration to authorities of the improvement in burden of illness;

•

limitations or warnings contained in a product’s approved labeling;

Table of Contents

•

payers’ level of restrictions and/or barriers to coverage;

•

the clinical indications for which a product is approved;

•

availability and perceived advantages of alternative treatments;

•

the effectiveness of our or future collaborators’ sales, marketing and distribution strategies; and

•

pricing and cost effectiveness.

We expect physicians’ inertia and skepticism to also be a significant barrier as we attempt to gain market penetration with our future products. We believe we will continue to need to finance lengthy and time-consuming clinical studies to provide evidence of the medical benefit of our products and resulting therapies in order to overcome this inertia and skepticism.

Overall, our efforts to educate the medical community on the benefits of any of our products or technologies for which we obtain marketing approval from the FDA or other regulatory authorities, including foreign regulatory authorities, and gain broad market acceptance may require significant resources and may never be successful. If our products and technologies do not achieve an adequate level of acceptance by physicians, pharmacists and patients, we may not generate sufficient revenue from these products to become or remain profitable.

All potential applications of our product candidates are investigational, which subjects us to development and marketing risks.

Our product candidates are at various stages of development. Successful development and market acceptance of our products is subject to developmental risks, including risk of negative clinical data from current and anticipated trials, failure of inventive imagination, ineffectiveness, lack of safety, unreliability, manufacturing hurdles, failure to receive necessary regulatory clearances or approvals, high commercial cost, preclusion or obsolescence resulting from third parties’ proprietary rights or superior or equivalent products, competition from copycat products and general economic conditions affecting purchasing patterns. There can be no assurance that we or our partners will successfully develop and commercialize our product candidates, or that our competitors will not develop competing technologies that are superior or less expensive. Failure to successfully develop and market our product candidates would have a substantial negative effect on our results of operations and financial condition. If we are unable to establish or sustain coverage and adequate reimbursement for any future product candidates from third-party payors, the adoption of those products and sales revenue will be adversely affected, which, in turn, could adversely affect the ability to market or sell those product candidates, if approved.

competing technologies that are superior or less expensive. Failure to successfully develop and market our product candidates would have a substantial negative effect on our results of operations and financial condition. If we are unable to establish or sustain coverage and adequate reimbursement for any future product candidates from third-party payors, the adoption of those products and sales revenue will be adversely affected, which, in turn, could adversely affect the ability to market or sell those product candidates, if approved.

We and our product candidates are subject to extensive regulation, and the requirements to obtain regulatory approvals in the United States and other jurisdictions can be costly, time-consuming and unpredictable. If we or our partners are unable to obtain timely regulatory approval for our product candidates, our business may be substantially harmed.

The worldwide regulatory process for our nanomedicine drug candidates can be lengthy and expensive, with no guarantee of approval.

Before any new drugs may be introduced to the U.S. market, the manufacturer generally must obtain FDA approval ~~through either an ANDA process for generic drugs off patent that allow for bioequivalence to an existing RLD or the lengthier NDA process~~, which typically requires multiple successful and successive clinical trials to generate clinical data supportive of safety and efficacy along with extensive pharmacodynamic and pharmacokinetic preclinical testing to demonstrate safety. ~~Our RNL product candidates are subject to the FDA’s 505(b)(1) NDA process. NDA drugs can take significant time due to the preclinical and clinical trial requirements.~~

There are numerous risks arising out of the regulation of our nanomedicine product candidates include the following:

•

we can provide no assurances that our current and future oncology drugs will meet all of the stringent government regulation in the United States under the FDCA, and/or in international markets such as the EU, by the EMA under its Medicinal Products Directive;

•

our nanomedicine product candidates, if approved, will still be subject to post-market reporting requirements for instances where the drug may have caused or contributed to the death or serious injury, or serious adverse events; and

•

there are no assurances that our product candidates will not have safety or effectiveness problems occurring after the drugs reach the market;

there are no assurances that regulatory authorities will not take steps to prevent or limit further marketing of the drug due to safety concerns; and

it is possible that the new legislation in our priority markets will yield additional regulatory requirements for therapeutic drugs for our nanomedicine product candidates.

Approved drug products are subject to ongoing regulatory requirements and oversight, including requirements related to manufacturing, quality control, conduct of post-marketing studies, labeling, packaging, storage, distribution, safety surveillance, import, export, advertising, promotion, recordkeeping and reporting. Regulatory authorities subject a marketed product, its manufacturer, and the manufacturing facilities to continual review and periodic inspections. We, our collaborators, and our and their respective contractors, suppliers and vendors, will be subject to ongoing regulatory requirements, including complying with regulations and laws regarding advertising, promotion and sales of products (including applicable anti-kickback, fraud and abuse and other health care laws and regulations), required submissions of safety and other post-market information and reports, registration requirements, cGMP regulations (including requirements relating to quality control and quality assurance, as well as the corresponding maintenance of records and documentation), and the requirements regarding the distribution of samples to physicians and recordkeeping requirements. Regulatory agencies may change existing requirements or adopt new requirements or policies that may be costly to comply with. We, our collaborators, and our and their respective contractors, suppliers, and vendors, may be slow to adapt or may not be able to adapt to these changes or new requirements.

Table of Contents

Failure to comply with regulatory requirements may result in any of the following:

•

restrictions on the marketing of our product candidates or manufacturing processes;

•

warning letters or untitled letters;

•

withdrawal of the products from the market;

•

voluntary or mandatory recall;

•

fines;

•

suspension or withdrawal of regulatory approvals;

•

suspension or termination of any of our ongoing clinical trials;

•

refusal to permit the import or export of our product candidates;

•

refusal to approve pending applications or supplements to approved applications that we submit;

•

product seizure;

•

injunctions; or

•

imposition of civil or criminal penalties.

43The future regulatory processes that will be applicable to LDTs are uncertain and may prevent us from obtaining required authorizations for the commercialization of our products and/or introduce additional costs associated with those products.

~~The~~Within ~~future~~the ~~regulatory~~laboratory, ~~processes~~most ~~that~~tests ~~will~~can be ~~applicable~~divided tointo ~~Laboratory~~two ~~Developed~~categories: ~~Tests~~in vitro diagnostics (IVDs) and laboratory developed tests (LDTs). IVDs are ~~uncertain~~commercially manufactured assays and ~~may~~make ~~prevent~~up usthe ~~from~~majority ~~obtaining~~of ~~required~~clinical ~~authorizations~~laboratory ~~for~~tests, such as those in a comprehensive metabolic panel (CMP) and a complete blood count (CBC). LDTs, on the ~~commercialization~~other ofhand, ~~our~~are ~~products~~developed by individual laboratories and/ overseen by highly trained and qualified laboratory directors. We re-introduced an LDT, the CNSide Test, in the U.S. in August 2025. If FDA were to determine that the CNSide Test is not an LDT or ~~introduce~~that ~~additional~~it ~~costs~~includes ~~associated~~components ~~with~~or ~~those~~accessories ~~products~~that are medical devices, then FDA could try to regulate the test or its components/accessories as medical devices.

Within the laboratory, most tests can be divided into two categories: in vitro diagnostics (IVDs) and laboratory developed tests (LDTs). IVDs are commercially manufactured assays and make up the majority of clinical laboratory tests, such as those in a comprehensive metabolic panel (CMP) and a complete blood count (CBC). LDTs, on the other hand, are developed by individual laboratories and overseen by highly trained and qualified laboratory directors. We plan to offer an LDT in the U.S. beginning in 2025.

In 1976, Congress passed the Medical Device Amendments to the FDCA. These amendments gave the FDA explicit authority to regulate medical devices. These included tests developed by manufacturers sold for commercial purposes to laboratories around the country. However, the amendments did not specifically include tests developed by laboratories for their own use. Then, in 1988, Congress passed the Clinical Laboratory Improvement Amendments (CLIA). These gave clinical laboratories the ability to develop and perform their own tests to fill gaps in available testing and provided the framework for LDT regulation. Today, all laboratories must have appropriate CLIA accreditation, overseen by the Centers for Medicare and Medicaid Services (CMS), to perform LDTs.

~~Historically,~~The ~~the~~ FDA has ~~exercised~~historically ~~enforcement~~taken ~~discretion~~the ~~for~~position ~~LDTs,~~that ~~allowing~~it ~~labs~~has the authority to ~~offer~~regulate ~~tests~~LDTs ~~with~~as ~~little~~IVD ~~input~~devices ~~from~~under the ~~agency. However~~FDCA, onalthough ~~May~~it 6,has ~~2024,~~generally ~~the~~exercised ~~FDA~~enforcement ~~issued~~discretion awith ~~final~~regard ~~rule~~to inLDTs. ~~which~~This itmeans ~~announced~~that iteven ~~was~~though ~~phasing~~the ~~out~~FDA ~~its~~believes ~~general~~it ~~enforcement~~can ~~discretion~~impose ~~approach~~regulatory sorequirements ~~that~~on LDTs, ~~manufactured~~such byas arequirements ~~laboratory~~to ~~will~~obtain ~~generally~~premarket ~~fall~~approval, ~~under~~de ~~the~~novo ~~same~~classification ~~enforcement~~or ~~approach~~clearance asof ~~medical devices. If implemented~~LDTs, ~~this~~it ~~phase~~has ~~out~~generally ofchosen ~~enforcement~~not ~~discretion~~to ~~will~~enforce ~~take~~those ~~place over several years~~requirements.

~~Congress~~On isMay ~~also~~6, ~~working~~2024, ~~on legislative language that would clarify~~ the FDA’s ~~authority~~issued ~~with~~a ~~respect to LDTs – and if enacted, would potentially supersede the~~ final rule. Inamending ~~this regard,~~ the ~~“Verifying~~definition ~~Accurate~~of ~~Leading-edge~~an ~~IVCT~~IVD ~~Development~~to ~~Act,”~~include ortests ~~VALID~~manufactured ~~Act,~~by ~~was~~a ~~most~~clinical ~~recently introduced in March 2023~~laboratory. This ~~The~~rule ~~bill proposes a risk-based approach that~~ would ~~subject~~have ~~many~~required LDTs to ~~FDA~~comply ~~regulation~~with bythe ~~creating~~same ageneral ~~new~~regulatory inrequirements ~~vitro~~as ~~clinical~~other ~~test,~~medical ~~or IVCT, category of regulated products~~devices. AsTwo ~~proposed,~~lawsuits ~~the~~challenging ~~bill~~FDA’s ~~would~~authority ~~grandfather~~to ~~many~~regulate ~~existing~~ LDTs—one ~~from~~by the ~~proposed~~American ~~premarket~~Clinical ~~approval,~~Laboratory ~~quality~~Association ~~systems,~~ and ~~labeling~~the ~~requirements, respectively, but would require such tests to comply with~~ other ~~regulatory~~by ~~requirements~~the ~~(e.g.,~~Association ~~registration/listing,~~for ~~adverse~~Molecular ~~event~~Pathology— ~~reporting).~~were Tofiled ~~market~~in afederal ~~high-risk~~district ~~IVCT,~~courts ~~reasonable~~in ~~assurance~~Texas ofin ~~analytical~~2024 and ~~clinical~~were ~~validity~~subsequently ~~for the intended use would be needed to be established~~consolidated. ~~Under~~On ~~VALID,~~March ~~a precertification process would be established that would allow a laboratory to establish that the facilities~~31, ~~methods~~2025, ~~and controls used in~~ the ~~development~~court ofissued ~~its~~an ~~IVCTs~~order ~~meet~~vacating ~~quality~~the ~~system~~final ~~requirements. If pre-certified~~rule, ~~low-risk~~thereby ~~IVCTs~~overturning ~~developed by~~ the ~~laboratory and falling within the scope of the FDA~~rulemaking’s ~~precertification~~associated ~~order would not be subject to test-specific pre-market review~~requirements. The ~~new~~district ~~regulatory~~court ~~framework~~ruled ~~would~~the ~~include quality control and post-market reporting requirements. The~~ FDA ~~would~~lacks ~~have~~jurisdiction ~~the authority~~ to ~~withdraw~~regulate ~~approvals~~LDTs ~~for~~because ~~IVCTs~~they ~~for~~do ~~various~~not ~~reasons,~~meet ~~including~~the ~~(for~~definition ~~example)~~of ~~if there were~~ a ~~reasonable~~medical ~~likelihood~~device ~~that~~under the ~~test~~FDC ~~would cause death or serious adverse health consequences~~Act. ~~However,~~The wegovernment ~~cannot~~did ~~predict~~not ~~if this (or any other bill) will be enacted in its current (or any other) form and cannot quantify the effect of such proposals on our business~~appeal.

ToLegislative ~~the~~proposals ~~extent~~addressing ~~that~~ the FDA’s ~~ultimately~~oversight ~~regulates~~of ~~certain~~ LDTs, ~~whether~~have ~~via~~been ~~final~~previously ~~rule,~~introduced. ~~final~~For ~~guidance~~example, orthe asVALID ~~instructed by Congress~~Act, ~~our~~introduced ~~LDTs~~in ~~may be subject to certain additional regulatory requirements. Complying with the FDA’s requirements may be expensive~~2021, ~~time-consuming,~~2023 and ~~subject~~again usin to2025, ~~significant~~would orhave ~~unanticipated~~established ~~delays.~~a ~~Insofar~~new asrisk-based weregulatory ~~may~~framework befor ~~required~~in tovitro ~~obtain~~clinical ~~premarket~~tests ~~clearance or approval to perform an LDT~~(IVCTs), wea ~~cannot~~category ~~assure~~which ~~you~~would ~~that~~have weincluded ~~will~~IVDs, beLDTs, ~~able~~collection todevices ~~obtain~~and ~~such~~instruments ~~authorization.~~used ~~Even~~with ~~if we obtain regulatory clearance or approval where required,~~ such ~~authorization may not be for the intended uses that we believe are commercially attractive or are critical to the commercial success of our~~ tests. AsIt ais ~~result,~~unclear ~~the~~whether ~~application of~~ the ~~FDA’s~~court ~~requirements~~decision towill ~~our~~renew ~~tests~~interest ~~could~~in ~~materially~~a ~~and~~legislative ~~adversely~~path ~~affect~~for ~~our~~LDT ~~business, financial condition, and results of operations~~regulation.

~~Compliance~~If ~~with~~ the ~~FDCA~~regulatory framework for aLDTs ~~medical~~changes ~~device~~in ~~includes~~the future, ~~among~~CNSide ~~other~~Diagnostics ~~things,~~may ~~registration~~also ~~and~~be ~~listing,~~required ~~quality~~to ~~system~~comply ~~regulations,~~with ~~and~~these ~~premarket~~FDA ~~authorization~~or other, different regulations. Failure to comply with applicable ~~FDA~~ regulatory requirements may trigger a range of enforcement actions, byand ~~the~~may ~~FDA,~~disqualify ~~including~~or ~~warning~~delay ~~letters,~~a ~~civil~~company ~~monetary~~from ~~penalties,~~launching ~~injunctions,~~an ~~criminal~~LDT ~~prosecution~~product, ~~recall~~ or ~~seizure,~~prevent ~~operating~~a ~~restrictions,~~company ~~partial~~with ~~suspension~~an orLDT ~~total~~on ~~shutdown~~the ofmarketing ~~operations,~~from ~~and~~continuing ~~denial of or challenges~~ to ~~applications~~sell ~~for~~their ~~clearance or approval, as well as significant adverse publicity~~test.

~~Risks~~Compliance ~~associated~~with the FDCA for a medical device includes, among other things, registration and listing, quality management system regulations, and premarket authorization. Failure to comply with applicable FDA regulatory requirements may trigger a range of enforcement actions by the ~~new~~FDA, ~~landscape~~including warning letters, civil monetary penalties, injunctions, criminal prosecution, recall or seizure, operating restrictions, partial suspension or total shutdown of ~~LDTs~~operations, ~~include~~and ~~but~~denial ~~are~~of ~~not~~or ~~limited~~challenges to: applications for clearance or approval, as well as significant adverse publicity.

Our inability to implement quality standards included in the new guidelines

Our inability to implement all FDA requirements for medical device LDTs

Backlog at the FDA for review of submission

Additional regulations being adopted by the FDA

Increased timeline to product launch, delaying revenue for the company

Increased regulatory oversight resulting in delays for product launch

Increased costs of product development and regulatory compliance, including:

More expansive validation study design

Hiring additional regulatory compliance talent

Hiring additional statistical experts

Other unanticipated costs

Changing, new and/or emerging government regulations, including healthcare legislative reform measures, may adversely affect us.

Our nanoparticle and microparticle technologies and pipeline oncology products and laboratory test are being developed under existing government criteria, which are subject to change in the future. Clinical and/or ~~pre-clinical~~preclinical criteria and cGMP manufacturing requirements may change and additional regulatory burdens may be imposed. Any regulatory review committees and advisory groups and any contemplated new guidelines may lengthen the regulatory review process, require us to perform additional studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval limitations or restrictions. As we advance our product candidates, we may be required to consult with these regulatory and advisory groups and comply with applicable guidelines. If we fail to do so, we may be required to delay or discontinue development of our product candidates. Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a product candidate to market could decrease our ability to generate sufficient revenue to maintain our business. Divergence in regulatory criteria for different regulatory agencies in international jurisdictions could result in the repeat of clinical studies and/or preclinical studies to satisfy local territory requirements, resulting in the repeating of studies and/or delays in the regulatory process. Some territories may require clinical data in their indigenous population, resulting in the repeat of clinical studies in whole or in part. Some territories may object to the formulation ingredients in the final finished product and may require reformulation to modify or remove objectionable components; resulting in delays in regulatory approvals. Such objectionable reformulations include, but are not limited to, human or animal components, Bovine Spongiform Encephalopathy and/or Transmissible Spongiform Encephalopathy risks, banned packaging components, prohibited chemicals, and banned substances. There can be no assurances that the FDA or foreign regulatory authorities will accept our pre-clinical and/or clinical data.

Table of Contents

may change and additional regulatory burdens may be imposed. Any regulatory review committees and advisory groups and any contemplated new guidelines may lengthen the regulatory review process, require us to perform additional studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval limitations or restrictions. As we advance our product candidates, we may be required to consult with these regulatory and advisory groups and comply with applicable guidelines. If we fail to do so, we may be required to delay or discontinue development of our product candidates. Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a product candidate to market could decrease our ability to generate sufficient revenue to maintain our business. Divergence in regulatory criteria for different regulatory agencies in international jurisdictions could result in the repeat of clinical studies and/or preclinical studies to satisfy local territory requirements, resulting in the repeating of studies and/or delays in the regulatory process. Some territories may require clinical data in their indigenous population, resulting in the repeat of clinical studies in whole or in part. Some territories may object to the formulation ingredients in the final finished product and may require reformulation to modify or remove objectionable components; resulting in delays in regulatory approvals. Such objectionable reformulations include, but are not limited to, human or animal components, Bovine Spongiform Encephalopathy and/or Transmissible Spongiform Encephalopathy risks, banned packaging components, prohibited chemicals, and banned substances. There can be no assurances that the FDA or foreign regulatory authorities will accept our preclinical and/or clinical data.

Anticipated or unanticipated changes in the way or manner in which the FDA or other regulators regulate products or classes and groups of products, including LDTs, can delay, further burden, or alleviate regulatory pathways that were once available to other products. There are no guarantees that such changes in the FDA’s or other regulators’ approach to the regulatory process will not deleteriously affect some or all of our product candidates or product applications.

In the United States and in some other jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the health care system that could prevent or delay marketing approval of our drug candidates, restrict or regulate post-approval activities, or affect our ability to profitably sell any drug candidates for which we obtain marketing approval, if any. Further, any increased scrutiny of the FDA’s approval process for drugs and biological products may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing testing and other requirements. There also are a number of state and local legislative and regulatory efforts related to drug pricing, including drug price transparency laws that apply to pharmaceutical manufacturers, which may have an impact on our business.

OnIf ~~May 6, 2024,~~ the ~~FDA~~regulatory ~~issued~~framework afor ~~final~~LDTs ~~rule~~changes in ~~which~~the itfuture, ~~announced~~CNSide itDiagnostics ~~was~~may ~~phasing~~also ~~out~~be ~~its~~required ~~general~~to ~~enforcement~~comply ~~discretion~~with ~~approach~~these soFDA ~~that~~or ~~LDTs~~other, ~~manufactured~~different byregulations. aFailure ~~laboratory~~to ~~will~~comply ~~generally~~with ~~fall~~applicable ~~under~~regulatory ~~the~~requirements ~~same~~may ~~enforcement~~trigger ~~approach~~a asrange ~~medical~~of ~~devices.~~enforcement ~~At this time it is unclear whether the current Administration will rescind~~actions, ~~revise,~~and ormay ~~continue~~disqualify ~~with this regulatory scheme~~ or ifdelay ita ~~will~~company befrom ~~superseded~~launching byan ~~Congressional~~LDT ~~action. Complying with these FDA requirements~~product, or ~~adapting~~prevent toa ~~revised~~company ~~requirements~~with ~~applicable~~an toLDT ~~LDTs,~~on ~~may~~the bemarketing ~~costly~~from ~~and~~continuing ~~may cause delays in our plans~~ to ~~commercialize~~sell ~~the~~their ~~CNSideTM Test~~test.

Table of Contents

In addition, the Drug Supply Chain Security Act enacted in 2013 imposes obligations on manufacturers of pharmaceutical products related to product tracking and tracing. In December 2019, the Further Consolidated Appropriations Act for 2020 was signed into law (P.L. 116-94) that includes a piece of bipartisan legislation called the Creating and Restoring Equal Access to Equivalent Samples Act of 2019 (the “CREATES Act”). The CREATES Act aims to address the concern articulated by both the FDA and others in the industry that some brand manufacturers have improperly restricted the distribution of their products, including by invoking the existence of a REMS for certain products, to deny generic and biosimilar product developers access to samples of brand products. The CREATES Act establishes a private cause of action that permits a generic or biosimilar product developer to sue the brand manufacturer to compel it to furnish the necessary samples on “commercially reasonable, market-based terms.” Whether and how generic and biosimilar product developments will use this new pathway, as well as the likely outcome of any legal challenges to provisions of the CREATES Act, remain highly uncertain and its potential effects on our future commercial products are unknown. Other legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products. We cannot be sure whether additional legislative changes will be enacted, or whether FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals, if any, of our drug candidates, may be or whether such changes will have any other impacts on our business. In addition, increased scrutiny by the U.S. Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing conditions and other requirements.

In the EU, similar political, economic and regulatory developments may affect our ability to profitably commercialize our product candidates. In addition to continuing pressure on prices and cost containment measures, legislative developments at the EU or EU Member State level may result in significant additional requirements or obstacles that may increase our operating costs.

We expect that other legislative or healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria, lower reimbursement, and additional downward pressure on the price that we will receive for any approved product. Any reduction in payments from Medicare or other government-funded programs may result in a similar 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 product candidates.

Healthcare reform measures could hinder or prevent the commercial success of our LDTs or any product candidate for which we obtain regulatory approval.

In the United States, there have been, and we expect there will continue to be, a number of legislative and regulatory changes to the healthcare system in ways that may harm our future revenues and profitability and the demand for our diagnostic tests or any product candidate for which we obtain regulatory approval. Federal and state lawmakers regularly propose and, at times, enact legislation that would result in significant changes to the healthcare system, some of which are intended to contain or reduce the costs of medical products and services. Current and future legislative proposals to further reform healthcare or reduce healthcare costs may limit coverage of or lower reimbursement for the procedures associated with the use of our diagnostic tests or product candidates for which we obtain regulatory approval. The effect of any healthcare reform initiative implemented in the future could impact our revenue from the sale of our diagnostic tests or product candidates for which we obtain regulatory approval. For example, the ACA, contains a number of provisions, including those governing enrollment in federal healthcare programs, reimbursement changes and fraud and abuse measures, all of which will impact existing government healthcare programs and will result in the development of new programs. Since the ACA was enacted, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could, among other things, affect pricing and third-party payment for our product candidates prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and negatively affect our ability to profitably sell any products for which we obtain marketing approval.

Several healthcare reform initiatives culminated in the enactment of the IRA, which, among other things, requires HHS to directly negotiate the selling price of a statutorily specified number of drugs and biologics each year that CMS reimburses under Medicare Part B and Part D. The negotiated price may not exceed a statutory ceiling price. Only high-expenditure single-source drugs that have been approved for at least seven years (11 years for single-source biologics) can qualify for negotiation, with the negotiated price taking effect two years after the selection year. For 2026, the first year in which negotiated prices become effective, CMS selected 10 high-cost Medicare Part D products in 2023, negotiations began in 2024, and the negotiated maximum fair price for each product has been announced. In addition, CMS has selected and announced the negotiated maximum fair price for 15 additional Medicare Part D drugs, which will become effective for negotiated maximum fair pricing in 2027. For 2028, CMS selected an additional 15 drugs, comprised of drugs covered under Medicare Part D and, for the first time, drugs payable under Medicare Part B. For 2029 and subsequent years, 20 Part B or Part D drugs will be selected. Currently, a drug or biological product that has an orphan drug designation for only one rare disease or condition will be excluded from the IRA’s price negotiation requirements, but loses that exclusion if it has designations for more than one rare disease or condition, or if is approved for an indication that is not within that single designated rare disease or condition, unless such additional designation or such disqualifying approvals are withdrawn by the time CMS evaluates the drug for selection for negotiation. However, as a result of a statutory amendment enacted in July 2025, beginning with the 2028 negotiated price applicability year, a drug may be designated for more than one rare disease or condition and still be excluded from price negotiation, as long as the only approved indications are for such rare diseases or conditions. The IRA also imposes rebates on Medicare Part B and Part D drugs whose prices have increased at a rate greater than the rate of inflation. The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as

Table of Contents

opposed to regulation, for the initial years. Manufacturers that fail to comply with the IRA may be subject to various penalties, some significant, including civil monetary penalties.

Further, at the U.S. state level, legislatures are increasingly enacting laws and implementing regulations designed to control pharmaceutical and biological product pricing, including price or reimbursement constraints, discount requirements, marketing cost disclosure and price increase transparency reporting, and programs designed to encourage importation from other countries and bulk purchasing.

Additional healthcare reform measures may be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products or otherwise negatively impact our business model. We expect pricing pressures will continue globally.

In both U.S. and non-U.S. markets, our ability to successfully commercialize and achieve market acceptance of our product candidates, if approved, depends in significant part on adequate financial coverage and reimbursement from third party payors, including governmental payors (such as the Medicare and Medicaid programs in the U.S.), managed care organizations and private health insurers. Without third party payor reimbursement, patients may not be able to obtain or afford prescribed medications. In addition, coverage and reimbursement guidelines and restrictions set by third party payors may have a significant impact on the prescribing physicians’ willingness and ability to prescribe our products. The demand for, and the profitability of, our products could be materially harmed if the state Medicaid programs, Medicare program, other healthcare programs in the U.S. or elsewhere, or third party commercial payors in the U.S. or elsewhere deny reimbursement for our products, limit the indications for which our products will be reimbursed, or provide reimbursement only on unfavorable terms.

As part of the overall trend toward cost containment, third party payors often require prior authorization for, and require reauthorization for continuation of, prescription products or impose step edits, which require prior use of another medication, usually a generic or preferred brand, prior to approving coverage for a new or more expensive product. Such restrictive conditions for reimbursement and an increase in reimbursement-related activities can extend the time required to fill prescriptions and may discourage patients from seeking treatment. We cannot predict actions that third party payors may take, or whether they will limit the access and level of reimbursement for our product candidates, if commercialized or refuse to provide any approvals or coverage.

Third party payors increasingly examine the cost-effectiveness of pharmaceutical products, in addition to their safety and efficacy, when making coverage and reimbursement decisions. We may need to conduct expensive pharmacoeconomic and/or clinical studies in order to demonstrate the cost-effectiveness of our products. If our competitors offer their products at prices that provide purportedly lower treatment costs than our products, or otherwise suggest that their products are safer, more effective or more cost-effective than our products, this may result in a greater level of access for their products relative to our products, which would reduce our sales and harm our results of operations. In some cases, for example, third party payors try to encourage the use of less expensive generic products through their prescription benefit coverage and reimbursement and co-pay policies. Because some of our product candidates, once commercialized, may compete in a market with both branded and generic products, obtaining and maintaining access and reimbursement coverage for our products may be more challenging than for products that are new chemical entities for which no therapeutic alternatives exist. If our competitors offer a clinical lab test that competes with our ~~CNSideTM~~CNSide Test but is viewed by clinicians or payers as being more cost effective or having greater clinical utility, we may not be able to realize the expected benefits of our test.

Some intellectual property that we have in-licensed has been discovered through government funded programs and thus may be subject to federal regulations such as “march-in” rights, certain reporting requirements and a preference for U.S.-based companies. Compliance with such regulations may limit our exclusive rights and limit our ability to contract with non-U.S. manufacturers.

Some of the intellectual property rights we have licensed are generated through the use of U.S. government funding and are therefore subject to certain federal regulations. As a result, the U.S. government may have certain rights to intellectual property embodied in our current or future product candidates pursuant to the Bayh-Dole Act of 1980 (the “Bayh-Dole Act”), and implementing regulations. These U.S. government rights in certain inventions developed under a government-funded program include a non-exclusive, non-transferable, irrevocable worldwide license to use inventions for any governmental purpose. In addition, the U.S. government has the right to require us or our licensors to grant exclusive, partially exclusive, or non-exclusive licenses to any of these inventions to a third party if it determines that: (i) adequate steps have not been taken to commercialize the invention; (ii) government action is necessary to meet public health or safety needs; or (iii) government action is necessary to meet requirements for public use under federal regulations (also referred to as “march-in” rights). The U.S. government also has the right to take title to these inventions if we, or the applicable licensor, fail to disclose the invention to the government and fail to file an application to register the intellectual property within specified time limits. These time limits have recently been changed by regulation and may change in the future. Intellectual property generated under a government funded program is also subject to certain reporting requirements, compliance with which may require us or the applicable licensor to expend substantial resources. In addition, the U.S. government requires that any products embodying the subject invention or produced through the use of the subject invention be manufactured substantially in the United States. The manufacturing preference requirement can be waived if the owner of the intellectual property can show that reasonable but unsuccessful efforts have been made to grant licenses on similar terms to potential licensees that would be likely to manufacture substantially in the United States or that under the circumstances domestic manufacture is not commercially feasible. This preference for U.S. manufacturers may limit our ability to contract with non-U.S. product manufacturers for products covered by such intellectual property. To the extent any of our

4642

~~current~~Table ~~or future intellectual property is generated through the use~~ of ~~U.S. government funding, the provisions of the Bayh-Dole Act may similarly apply.~~Contents

if the owner of the intellectual property can show that reasonable but unsuccessful efforts have been made to grant licenses on similar terms to potential licensees that would be likely to manufacture substantially in the United States or that under the circumstances domestic manufacture is not commercially feasible. This preference for U.S. manufacturers may limit our ability to contract with non-U.S. product manufacturers for products covered by such intellectual property. To the extent any of our current or future intellectual property is generated through the use of U.S. government funding, the provisions of the Bayh-Dole Act may similarly apply.

In September 2020, the FDA granted ~~both~~ orphan drug designation ~~and~~to ~~Fast~~rhenium ~~Track~~(186Re) ~~designation~~obisbemeda ~~to REYOBIQ™~~ for the treatment of patients with GBM. In ~~November 2021, the FDA granted Fast Track designation to REYOBIQ™ for the treatment of patients with LM. In~~ March 2025, the FDA granted orphan drug designation to ~~REYOBIQ™~~rhenium (186Re) obisbemeda for the treatment of LM in patients with lung cancer. A product candidate that receives orphan drug designation can benefit from potential commercial benefits following approval. Under the U.S. Orphan Drug Act, the FDA may designate a product candidate as an orphan drug if it is intended to treat a rare disease or condition, defined as affecting a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States. In the EU, the EMA’s Committee for Orphan Medicinal Products grants orphan drug designation to promote the development of products that are intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than 10,000 persons in the EU. Currently, this designation makes the product eligible for market exclusivity in the U.S. and the EU for seven years and ten years, respectively, if a product is the first such product approved for such orphan indication. This market exclusivity does not, however, ~~pertain~~block to indications other than those for which the drug is designated and indicated for, which can be narrower than the orphan drug designation, nor does it prevent drug products containing a different active moiety from receiving orphan designations or approvals in these same indications. Further, even after an orphan drug is approved, the FDA can subsequently approve a drug with similar chemical structure for the same indication if the FDA concludes that the new drug is clinically superior to the orphan product or a market shortage occurs. In the EU, orphan exclusivity may be reduced to six years if the drug no longer satisfies the original designation criteria or can be lost altogether if the marketing authorization holder consents to a second orphan drug application or cannot supply enough drug, or when a second applicant demonstrates its drug is “clinically superior” to the original orphan drug. Notwithstanding orphan drug designation for some of our product candidates, we may not enjoy market exclusivity in a particular market, and if we fail to obtain or maintain orphan drug designation or other regulatory exclusivity for some of our product candidates, our competitive position would be harmed.

Fast Track Designation by the FDA may not lead to a faster development or regulatory review or approval process.

We have obtained Fast Track Designation for rhenium (186Re) obisbemeda for multiple indications. We may seek Fast Track Designation for other potential indications for rhenium (186Re) obisbemeda, or for one or more of our future product candidates. If a drug is intended for the treatment of a serious or life-threatening condition and the drug demonstrates the potential to address unmet medical needs for this condition, the product sponsor may apply for FDA Fast Track Designation. The FDA has broad discretion whether or not to grant this designation, so even if we believe a particular product candidate is eligible for this designation, we cannot assure you that the FDA would decide to grant it. Even if we do receive Fast Track Designation, 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.

A Rare Pediatric Disease designation by the FDA does not guarantee that the NDA for the product will qualify for a priority review voucher upon approval, and it does not lead to a faster development or regulatory review process, or increase the likelihood that rhenium (186Re) obisbemeda or our future product candidates will receive marketing approval.

Under the Rare Pediatric Disease Priority Review Voucher program, upon the approval of a qualifying NDA for the treatment of a rare pediatric disease, the sponsor of such an application would be eligible for a rare pediatric disease priority review voucher that can be used to obtain priority review for a subsequent Biologics License Application or NDA. As part of our business strategy, we may seek Rare Pediatric Disease designations for rhenium (186Re) obisbemeda or any other future product candidates. Under the current sunset provisions, a product candidate is eligible to receive a voucher if it is approved before September 30, 2029. However, there is no guarantee that rhenium (186Re) obisbemeda or our future product candidates will be designated or that any of our product candidates will be approved, and, therefore, we may not be in a position to obtain any priority review vouchers. Additionally, designation of a drug for a rare pediatric disease does not guarantee that an NDA will meet the eligibility criteria for a rare pediatric disease priority review voucher at the time the application is approved. Finally, a Rare Pediatric Disease Designation does not lead to faster development or regulatory review of the product or increase the likelihood that it will receive marketing approval.

If we decide to pursue accelerated approval for any of our product candidates, it may not lead to a faster development or regulatory review or approval process and does not increase the likelihood that our product candidates will receive marketing approval.

In the future, we may decide to pursue accelerated approval for one or more of our product candidates. Under the accelerated approval program, the FDA may grant accelerated approval to a product candidate designed to treat a serious or life-threatening condition that provides meaningful advantage over available therapies upon a determination that the product candidate has an effect on a surrogate endpoint or intermediate clinical endpoint that is reasonably likely to predict clinical benefit. The FDA considers a clinical benefit to be a positive therapeutic effect that is clinically meaningful in the context of a given disease, such as irreversible morbidity or mortality. For the purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign, or other

Table of Contents

measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit. An intermediate clinical endpoint is a clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit. The accelerated approval pathway may be used in cases in which the advantage of a new drug over available therapy may not be a direct therapeutic advantage but is a clinically important improvement from a patient and public health perspective. For products granted accelerated approval, sponsors are required to verify and describe the product’s anticipated clinical benefit generally in the form of confirmatory trials. These confirmatory trials must be completed with due diligence, and the FDA is authorized to require a post-approval trial to be underway prior to approval or within a specified time period following approval. The FDA is also required to specify conditions of any required post-approval trial. Sponsors are required to submit progress reports for required post-approval studies and any conditions required by the FDA. The FDA may initiate enforcement action for the failure to conduct with due diligence a required post-approval trial, including a failure to meet any required conditions, which may include enrollment targets, the study protocol and study milestones, specified by the FDA, or to submit timely reports.

In addition, all promotional materials for products approved under the accelerated approval pathway are subject to prior review by the FDA. If the FDA were to object to promotional pieces regarding products approved via accelerated approval, a company may be required to revise those materials, or be subject to untitled or warning letters.

If we experience an interruption in supply from a material sole source supplier, our business may be harmed.

We acquire some of our components and other raw materials from sole source suppliers. If there is an interruption in supply of our raw materials from a sole source supplier, for any reason, there can be no assurance that we will be able to obtain adequate quantities of the raw materials within a reasonable time or at commercially reasonable prices. Interruptions in supplies due to pricing, timing, availability, or other issues with our sole source suppliers could have a negative impact on our ability to manufacture products and product candidates, which in turn could adversely affect the development and commercialization of our nanomedicine product candidates and cause us to potentially breach our supply or other obligations under our agreements with certain other counterparties.

We are dependent on sole source suppliers to manufacture the active pharmaceutical ingredients (“API”) and certain other components of our nanomedicine product candidates. There is no assurance that these sole source suppliers will enter into supply agreements with us to provide contractual assurance to us around supply and pricing. Regardless of whether a sole source supplier enters into a written supply arrangement with us, such supplier could still delay, suspend, or terminate supply of raw materials to us for a number of reasons, including manufacturing or quality issues, payment disputes with us, bankruptcy or insolvency, or other occurrences.

Manufacturing or quality assurance difficulties at our contractors and suppliers, the failure or refusal of a supplier or contract manufacturer to supply contracted quantities, or increases in demand on a supplier with constrained capacity could result in delays and disruptions in the manufacturing, distribution, and sale of our products and /or product candidates, leading to lost revenue or reduced market opportunities. Supply constraints may also lead to pauses, discontinuations, or other product availability issues in one or more markets, which could have a material adverse effect on our consolidated results of operations and cash flows. Further, cost inflation and global transportation and logistics challenges, as well as tight labor markets, have caused, and in the future may cause, delays in, and increase costs related to, distribution of our products, the construction or other acquisition of additional manufacturing capacity, procurement activity, and supplier or contract manufacturer arrangements. These disruptions and challenges could result from actual or perceived quality, oversight, or regulatory compliance problems; natural disasters (including increased instances or severity of natural disasters or other events that may be due to climate change), public health outbreaks, epidemics, or pandemics; periods of uneven economic growth or downturns; emergence or escalation of, and responses to international tension and conflicts; equipment, mechanical, data, or information technology system (“IT system”) vulnerabilities, such as system inadequacies, inadequate controls or procedures, operating failures, unauthorized access, service interruptions or failures, security breaches, malicious intrusions, theft, exfiltration, ransomware or other cyber-attacks from a variety of sources; labor shortages; challenges and complexities in manufacturing new drug modalities; contractual disputes with our suppliers and contract manufacturers; vertical integration by competitors within our supply chain; or inability to obtain single-source or other raw or intermediate materials.

If a sole source supplier ceases supply of raw materials necessary, there is no guarantee that we will find an alternative supplier for the necessary raw materials on terms acceptable to us, or at all. Finding alternative suppliers if and as necessary due to geopolitical developments or otherwise may not be feasible or could take a significant amount of time and involve significant expense due to the nature of our products and product candidates. Further the qualification process for a new vendor could take months or years, and any such day in qualification could significantly harm our business.

nature of our products and product candidates. Further the qualification process for a new vendor could take months or years, and any such day in qualification could significantly harm our business.

We may engage in strategic transactions that could impact our liquidity, increase our expenses, and present significant distractions to our management.

From time to time, we may consider strategic transactions, such as acquisitions of companies, asset purchases and out-licensing or in-licensing of products, product candidates or technologies. Growth of the nanomedicine business will require significant management time and attention. Further, the future growth of our business will depend in part on our ability to in-license or otherwise acquire the rights to additional product candidates or technologies. We cannot assure you that we will be able to in-license or acquire the rights to any product candidates or technologies from third parties on acceptable terms or at all.

Table of Contents

Additional potential transactions that we may consider include a variety of different business arrangements, including spin-offs, strategic partnerships, joint ventures, restructurings, divestitures, business combinations and investments. Any such transaction may require us to incur non-recurring or other charges, may increase our near and long-term expenditures and may pose significant integration challenges or disrupt our management or business, which could adversely affect our operations and financial results. For example, these transactions may entail numerous operational and financial risks, including:

•

exposure to unknown liabilities;

•

disruption of our business and diversion of our management’s time and attention in order to develop acquired products, product candidates or technologies;

•

incurrence of substantial debt or dilutive issuances of equity securities to pay for acquisitions;

•

higher than expected acquisition and integration costs;

•

write-downs of assets or goodwill or impairment charges;

•

increased amortization expenses;

•

difficulty and cost in combining the operations and personnel of any acquired businesses with our operations and personnel;

•

impairment of relationships with key suppliers or customers of any acquired businesses due to changes in management and ownership; and

•

inability to retain key employees of any acquired businesses.

The in-licensing and acquisition of these technologies is a competitive area, and a number of more established companies are also pursuing strategies to license or acquire product candidates or technologies that we may consider attractive. In addition, companies that perceive us to be a competitor may be unwilling to license rights to us. Furthermore, we may be unable to identify suitable product candidates or technologies within our area of focus. If we are unable to successfully obtain rights to suitable product candidates or technologies or to successfully complete any additional transactions of the nature described above, our business, financial condition and prospects could suffer. In addition, even if we are able to successfully complete any additional transactions of the nature described above, any additional transactions that we do complete could have a material adverse effect on our business, results of operations, financial condition, and prospects.

We must maintain quality controls and compliance with manufacturing standards.

The manufacture of our product candidates is, and the manufacture of any future drug, device, and/or cell-related therapeutic products would be, subject to periodic inspection by regulatory authorities and distribution partners. The manufacture of drug and device products for human use is subject to extensive regulation and inspection from time to time by the FDA for compliance with the FDA’s cGMP, the ~~Quality System Regulation (“QSR”)~~QMSR, as well as equivalent requirements and inspections by state and foreign. regulatory authorities. There can be no assurance that the FDA or other authorities will not, during the course of an inspection of existing or new facilities, identify what they consider to be deficiencies in our compliance with ~~QSRs~~the QMSRs or other requirements and request, or seek remedial action.

Failure to comply with such regulations or a potential delay in attaining compliance may adversely affect our manufacturing activities and could result in, among other things, injunctions, civil penalties, FDA refusal to grant pre- market approvals, authorizations, or clearances of future or pending product submissions, fines, recalls, import or seizures of products, total or partial suspensions of production and criminal prosecution. There can be no assurance that after such occurrences that we will be able to obtain additional necessary regulatory approvals, authorizations, or clearances on a timely basis, if at all. Delays in receipt of or failure to receive such approvals, authorizations, or clearances, or the loss of previously received approvals, authorizations, or clearances could have a substantial negative effect on our results of operations and financial condition.

If we are unable to identify, hire and/or retain key personnel, we may not be able to sustain or grow our business.

We maintain a small executive team. Our ability to operate successfully and manage our potential future growth depends significantly upon our ability to attract, retain, and motivate highly skilled and qualified research, technical, clinical, regulatory, sales, marketing, managerial and financial personnel. We compete for talent with numerous companies, as well as universities and non-profit research organizations. In the future, we may hire a significant number of scientists, quality and regulatory personnel, and other technical staff with the requisite expertise to support and expand our nanomedicine business. The manufacturing of our oncology drug assets is a highly complex process that requires significant experience and know-how. If we are unable to attract personnel with the necessary skills and experience to reestablish and expand our nanomedicine business, which is currently conducted out of our Houston, Texas facility, our business could suffer.

4845

~~highly~~Table complex process that requires significant experience and know-how. If we are unable to attract personnel with the necessary skills and experience to reestablish and expand our nanomedicine business, which is currently conducted out of ~~our Houston, Texas facility, our business could suffer.~~Contents

Our future success also depends on the personal efforts and abilities of the principal members of our senior management and scientific staff to provide strategic direction, manage our operations, and maintain a cohesive and stable environment. In particular, we are highly dependent on our executive officers, especially Marc Hedrick, M.D., our Chief Executive Officer. Given his leadership, extensive technical, scientific, and financial expertise and management and operational experience, if we were unable to retain the services of Dr. Hedrick for any reason, it would materially and adversely impact our business and operations. Further, the loss of services of Dr. Hedrick or any other executive officer could result in product development delays or the failure of our collaborations with current and future collaborators, which, in turn, may hurt our ability to develop and commercialize products and generate revenue. We do not maintain key man life insurance on the lives of any of the members of our senior management. The loss of key personnel for any reason or our inability to hire, retain, and motivate additional qualified personnel in the future could prevent us from sustaining or growing our business. The loss of services of any of our personnel, including Dr. Hedrick, particularly for an extended period, would likely result in product development delays or the failure of our collaborations with current and future collaborators, which, in turn, may impede or delay our ability to develop and commercialize products and generate revenue. In addition, it could also result in difficulty to obtain additional funding for our development of products and our future operations.

We face potential product liability exposure, and if successful claims are brought against us, we may incur substantial liability if our insurance coverage for those claims is inadequate.

The clinical use of our product candidates exposes us to the risk of product liability claims. This risk exists even if a product or product candidate is approved for commercial sale by applicable regulatory authorities and manufactured in facilities regulated by such authorities. Our product candidates are designed to affect important bodily functions and processes. Any side effects, manufacturing defects, misuse, or abuse associated with our product candidates could result in injury to a patient or even death. For example, ~~REYOBIQ™~~rhenium (186Re) obisbemeda and 188RNL-BAM are cytotoxic, or toxic to living cells, and, if incorrectly or defectively manufactured or labeled, or incorrectly dosed or otherwise used in a manner not contemplated by its label, could result in patient harm and even death. In addition, a liability claim may be brought against us even if our product candidates merely appear to have caused an injury.

Product liability claims may be brought against us by consumers, health care providers, pharmaceutical companies or others selling or otherwise coming into contact with our products or product candidates, if approved, among others. If we cannot successfully defend ourselves against product liability claims, we will incur substantial liabilities. In addition, regardless of merit or eventual outcome, product liability claims may result in:

•

the inability to commercialize our product candidates;

•

decreased demand for our product candidates, if approved;

•

impairment of our business reputation;

•

product recall or withdrawal from the market;

•

withdrawal of clinical trial participants;

•

costs of related litigation;

•

distraction of management’s attention from our primary business;

•

substantial monetary awards to patients or other claimants; or

•

loss of revenue.

We have obtained product liability insurance coverage for clinical trials with a $10 million per occurrence and annual aggregate coverage limit. Our insurance coverage may not be sufficient to cover all of our product liability related expenses or losses and may not cover us for any expenses or losses we may suffer. Moreover, insurance coverage is becoming increasingly expensive, and, in the future, we may not be able to maintain insurance coverage at a reasonable cost, in sufficient amounts or upon adequate terms to protect us against losses due to product liability. If we determine that it is prudent to increase our product liability coverage, we may be unable to obtain this increased product liability insurance on commercially reasonable terms or at all. Large judgments have been awarded in class action or individual lawsuits based on drugs that had unanticipated side effects. A successful product liability claim or series of claims brought against us could cause our stock price to decline and, if judgments exceed our insurance coverage, could decrease our cash and have a material adverse effect on our business, results of operations, financial condition and prospects.

Throughout the clinical trial process, we may obtain the health information of our trial subjects. There are a number of state, federal and international laws protecting the privacy and security of health information and personal data. For example, HIPAA imposes privacy, security, breach reporting obligations, and mandatory contractual terms on covered entity health care providers, health plans, and health care clearinghouses, as well as their “business associates” – certain persons or covered entities that create, receive, maintain, or transmit protected health information in connection with providing a specified service or performing a function on behalf of a covered entity. We could potentially be subject to criminal penalties if we, our affiliates, or our agents knowingly receive individually identifiable health information maintained by a HIPAA-covered entity in a manner that is not authorized or permitted by HIPAA. The Federal Trade Commission ("FTC") also sets expectations for taking appropriate steps to safeguard consumers' personal information, and providing a level

4946

orTable ~~transmit protected health information in connection with providing a specified service or performing a function on behalf~~ of a covered entity. We could potentially be subject to criminal penalties if we, our affiliates, or our agents knowingly receive individually identifiable health information maintained by a HIPAA-covered entity in a manner that is not authorized or permitted by HIPAA. The Federal Trade Commission ("FTC") also sets expectations for taking appropriate steps to safeguard consumers' personal information, and providing a level of privacy or security commensurate to promises made to individuals. The FTC expects a company's data privacy and security measures to be reasonable and appropriate in light of the sensitivity and volume of consumer information it holds, the size and complexity of its business, and the cost of available tools to improve security and reduce vulnerabilities. Failure to meet these standards may constitute unfair or deceptive acts or practices in violation of Section 5 of the FTC Act. The FTC also has the power to enforce the Health Breach Notification Rule, which imposes notification obligations on companies for breaches of certain health information contained in personal health records. Enforcement by the FTC under the FTC Act and Health Breach Notification Rule can result in civil penalties or enforcement actions.Contents

of privacy or security commensurate to promises made to individuals. The FTC expects a company's data privacy and security measures to be reasonable and appropriate in light of the sensitivity and volume of consumer information it holds, the size and complexity of its business, and the cost of available tools to improve security and reduce vulnerabilities. Failure to meet these standards may constitute unfair or deceptive acts or practices in violation of Section 5 of the FTC Act. The FTC also has the power to enforce the Health Breach Notification Rule, which imposes notification obligations on companies for breaches of certain health information contained in personal health records. Enforcement by the FTC under the FTC Act and Health Breach Notification Rule can result in civil penalties or enforcement actions.

Most states have laws requiring notification of affected individuals and state regulators (breach notification laws) in the event of a breach of personal information, which is a broader class of information than the health information protected by HIPAA. Many state laws impose significant data security requirements, such as encryption or mandatory contractual terms to ensure ongoing protection of personal information. For example, in California, the California Consumer Privacy Act, as amended by the California Privacy Rights Act (“CCPA”) establishes certain requirements for data use and sharing transparency and creates new data privacy rights for California consumers, as that term is defined by law. Failure to comply with the CCPA may result in, among other things, significant civil penalties and injunctive relief, or statutory or actual damages. In addition, California consumers have the right to bring a private right of action in connection with certain types of incidents. These claims may result in significant liability and damages. Other jurisdictions have enacted or proposed similar legislation and/or regulations, such as consumer privacy laws that went into effect in 2023 in Virginia, Colorado, Utah, and Connecticut. Health-specific Consumer privacy laws were also passed in multiple other states, including consumer health privacy laws in Washington and Nevada, which govern consumer health data.

Activities outside of the U.S. implicate local and national data protection standards, impose additional compliance requirements and generate additional risks of enforcement for non-compliance. For example, the EU’s General Data Protection Regulation, including as implemented in the UK (collectively “GDPR”) imposes fines of up to EUR 20 million or 4% of the annual global revenue of a noncompliant company, whichever is greater. The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with data protection authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR. Canada’s Personal Information Protection and Electronic Documents Act and other data protection, privacy and similar national, state/provincial and local laws may also restrict the access, use and disclosure of patient health information abroad. Moreover, as a result of the broad scale release and availability of Artificial Intelligence (AI) technologies such as generative AI, there is a global trend towards more regulation (e.g., the EU AI Act and AI laws passed in U.S. states) to ensure the ethical use, privacy, and security of AI and the data that it processes. Compliance with such laws will likely be an increasing and substantial cost in the future. We may be required to expend significant capital and other resources to ensure ongoing compliance with applicable privacy and data security laws, to protect against security breaches and hackers, or to alleviate problems caused by such breaches. Compliance with these laws is difficult, constantly evolving, time consuming, and requires a flexible privacy framework and substantial resources. Compliance efforts will likely be an increasing and substantial cost in the future.

We and our collaborators are subject to various federal, state, and local environmental laws, rules and regulations, including those relating to discharge of materials into the air, water and ground, those relating to manufacturing, storage, use, transportation and disposal of hazardous and biological materials, and those relating to the health and safety of employees with respect to laboratory activities required for the development of our products and activities. In particular, our nanomedicine products and processes involve the controlled storage, use and disposal of certain cytotoxic, or toxic to living cells, materials. Even if we and these suppliers and collaborators comply with the standards prescribed by law and regulation, the risk of accidental contamination or injury from hazardous materials, or other violations of applicable environmental laws, rules or regulations cannot be completely eliminated. In the event of any violation of such laws, rules or regulations, we could be held liable for any damages that result, and any liability could exceed the limits or fall outside the coverage of any insurance we may obtain and could exceed our financial resources. We may not be able to maintain insurance on acceptable terms, or at all. We may incur significant costs in complying with environmental laws, rules and regulations.

We ~~recently acquired the CNSideTM diagnostic portfolio, and we~~ may not be successful in our efforts to develop, fully utilize and monetize itthe CNSide diagnostic portfolio.

In April 2024, we completed the acquisition of substantially all of the right, title and interest in ~~CNSideTM~~CNSide, including the CNSide Test, which is designed to detect, quantify, and monitor tumor status in LM. We are currently evaluating and developing our business plan for developing the ~~CNSideTM~~CNSide diagnostic portfolio alongside our lead radio therapeutic candidate, rhenium (186Re) obisbemeda, and seeking partnering opportunities for ~~CNSideTM~~CNSide but there can be no assurances that we will be able to develop the technology to allow for commercial applications, or successfully utilize and fully integrate CNSide into our operations. We may not generate revenues from or realize the anticipated benefits of CNSide within our expected timeline or at all.

for commercial applications, or successfully utilize and fully integrate CNSideTM into our operations. We may not generate revenues from or realize the anticipated benefits of CNSideTM within our expected timeline or at all.

Clinical laboratories in the U.S. must maintain compliance with the federal CLIA standards and with applicable state law licensure requirements, and if we are unable to do so we may be unable to offer the ~~CNSideTM~~CNSide Test to patients. In order to be commercially viable, clinical lab tests must be covered and reimbursed by third party payers. If payers fail to cover the test, impose restrictions on the scope of coverage, or do not provide sufficient reimbursement for the CNSideTM Test we may be unable to realize the expected benefits of the test and may not be able to offer it within the expected timeline, or at all.

Table of Contents

coverage, or do not provide sufficient reimbursement for the CNSide Test we may be unable to realize the expected benefits of the test and may not be able to offer it within the expected timeline, or at all.

Healthcare providers, including physicians, and third-party payors in the U.S. and elsewhere will play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval and the ordering of the ~~CNSideTM~~CNSide Test. 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 healthcare laws, including, without limitation, the federal Anti-Kickback Statute, the federal civil and criminal false claims laws, the Physician Payments Sunshine Act and regulations promulgated under such laws. These laws will impact, among other things, our clinical research, proposed sales, marketing and educational programs, and other interactions with healthcare professionals and patients. 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 are described in greater detail in Item 1: Business: Other U.S. Healthcare Laws and Compliance Requirements.

Because of the breadth of these laws and the narrowness of the statutory exceptions and regulatory 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 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 penalties, including, without limitation, civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from participating in federal and state 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, contractual damages, diminished profits and future earnings, reputational harm and the curtailment or restructuring of our operations, any of which could harm our business.

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. Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will 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 a healthcare company may run afoul of one or more of the requirements.

The diagnostic testing industry is subject to rapid change, which could make our current or future products obsolete.

The diagnostic testing industry is characterized by rapid changes, including technological and scientific breakthroughs, developments related to application of generative artificial intelligence (“AI”), frequent new product introductions and enhancements and evolving industry standards, all of which could make our current products and the other products we are developing obsolete. The future success of our products will depend on our ability to keep pace with the evolving needs of clinicians and patients on a timely and cost-effective basis and to pursue new market opportunities that develop as a result of scientific and technological advances. In recent years, there have been numerous advances in technologies relating to the diagnosis and treatment of cancer. There have also been advances in methods used to analyze very large amounts of molecular information. We must continuously enhance our existing products and develop new products to keep pace with evolving standards of care. If we do not update our products to reflect new scientific knowledge about cancer biology, information about new cancer therapies or relevant clinical studies, our products could become obsolete and sales of our current products and any new products we develop could decline or fail to grow as expected.

Risks Relating to Our Intellectual Property

Our success depends in part on our ability to protect our intellectual property.

Our success depends in part on our ability to obtain and maintain patent, trademark, and trade secret protection of our platform technology and current product candidates, including but not limited to our nanomedicine product candidates, including ~~REYOBIQ™~~rhenium (186Re) obisbemeda and 188RNL-BAM, and our ~~CNSideTM~~CNSide Platform, as well as successfully defending our intellectual property against third-party challenges. Our ability to stop unauthorized third parties from making, using, selling, offering to sell, or importing our platform technology and/or our product candidates is dependent upon the extent to which we have rights under valid and enforceable patents or trade secrets that cover these activities.

The degree of future protection for our proprietary rights is uncertain because legal means afford only limited protection and may not adequately protect our rights or permit us to gain or keep our competitive advantage. For example:

5148

~~we,~~Table ~~NanoTx,~~of ~~or UTHSCSA, as the case may be, might not have been the first to file patent applications for REYOBIQ™ or 188RNL-BAM;~~ Contents

•

we, NanoTx, or ~~Biocept~~UTHSCSA, as the case may be, might not have been the first to file patent applications for ~~the~~rhenium ~~CNSideTM~~(186Re) ~~Platform~~obisbemeda or 188RNL-BAM;

•

we, or Biocept, as the case may be, might not have been the first to file patent applications for the CNSide Platform;

•

it is possible that our pending patent applications will not result in issued patents;

•

it is possible that there are dominating patents to our product candidates of which we are not aware;

•

it is possible that there are prior public disclosures that could invalidate our patents, of which we are not aware;

•

it is possible that others may circumvent our patents;

•

it is possible that there are unpublished applications or patent applications maintained in secrecy that may later issue with claims covering our product candidates or technology similar to ours;

•

the claims of our patents or patent applications, if and when issued, may not cover our system or products, or our system or product candidates;

•

our owned or in-licensed issued patents may not provide us with any competitive advantages, or may be narrowed in scope, be held invalid or unenforceable as a result of legal administrative challenges by third parties;

•

others may be able to make or use compounds that are the same or similar to the ~~REYOBIQ™~~rhenium (186Re) obisbemeda or 188RNL-BAM product candidates but that are not covered by the claims of our patents;

•

we may not be able to detect infringement against our patents, which may be especially difficult for manufacturing processes or formulation patents, such as the patents/applications related to ~~REYOBIQ™~~rhenium (186Re) obisbemeda or 188RNL-BAM;

•

the API used in ~~REYOBIQ™~~rhenium (186Re) obisbemeda, 186-Re, is routinely produced in nuclear reactors or at a particle accelerator and is commercially available as 186-Re Sulfide for isotropic radiation synovectomy of medium sized joints and in developing countries as 186-Re-HEDP for bone pain palliation;

•

we may not develop additional proprietary technologies for which we can obtain patent protection; or

•

the patents of others may have an adverse effect on our business.

The patent positions of pharmaceutical, biopharmaceutical and medical device companies can be highly uncertain and involve complex legal and factual questions for which important legal principles remain unresolved. No consistent policy regarding the breadth of claims allowed in patents in these fields has emerged to date in the United States. There have been recent changes regarding how patent laws are interpreted, and both the USPTO and Congress have recently made significant changes to the patent system. There have been three U.S. Supreme Court decisions that now show a trend of the Supreme Court which is distinctly negative on patents. The trend of these decisions along with resulting changes in patentability requirements being implemented by the USPTO could make it increasingly difficult for us to obtain and maintain patents on our product candidates. We cannot accurately predict future changes in the interpretation of patent laws or changes to patent laws which might be enacted into law. Those changes may materially affect our patents, our ability to obtain patents and/or the patents and applications of our collaborators and licensors. The patent situation in these fields outside the United States is even more uncertain. Changes in either the patent laws or in interpretations of patent laws in the United States and other countries may diminish the value of our intellectual property or narrow the scope of our patent protection. Accordingly, we cannot predict the breadth of claims that may be allowed or enforced in the patents we own or to which we have a license or third-party patents.

Intellectual property law outside the United States is uncertain and in many countries is currently undergoing review and revisions. The laws of some countries do not protect our patent and other intellectual property rights to the same extent as United States laws. Third parties may attempt to oppose the issuance of patents to us in foreign countries by initiating opposition proceedings. Opposition proceedings against any of our patent filings in a foreign country could have an adverse effect on our corresponding patents that are issued or pending in the United States. It may be necessary or useful for us to participate in proceedings to determine the validity of our patents or our competitors’ patents that have been issued in countries other than the United States. This could result in substantial costs, divert our efforts and attention from other aspects of our business, and could have a material adverse effect on our results of operations and financial condition.

Failure to obtain or maintain patent protection or protect trade secrets, for any reason (or third-party claims against our patents, trade secrets, or proprietary rights, or our involvement in disputes over our patents, trade secrets, or proprietary rights, including involvement in litigation), could have a substantial negative effect on our results of operations and financial condition.

52If we do not obtain patent term extension for any product candidates we may develop, our business may be materially harmed.

Depending upon the timing, duration and specifics of any FDA marketing approval of any product candidates we may develop, one or more of our U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Amendments. The Hatch-Waxman Amendments permit a patent extension term of up to five years as compensation for patent term lost during the FDA regulatory review process. A patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent per product may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended. The application for the extension must be submitted prior to the expiration of the patent for which extension is sought and within 60 days of FDA approval. However, we may not be granted a patent term extension because of, for example, the failure to exercise due diligence during the testing phase or regulatory review process, the failure to apply within applicable deadlines, the failure to apply prior to expiration of relevant patents, or any other failure to satisfy applicable requirements. Moreover, the applicable time period or the scope of patent protection afforded could be less than we request. In addition, to the extent we wish to pursue patent term extension based on a patent that we in-license from a third party, we would need the cooperation of that third party. If we are unable to obtain patent term extension or term of any such extension is

Table of Contents

less than we request, our competitors may obtain approval of competing products following our patent expiration, and our business, financial condition, results of operations, and prospects could be materially harmed.

We may not be able to protect our trade secrets.

We may rely on trade secrets to protect our technology, especially with respect to the nanomedicine products, as well as in areas where we do not believe patent protection is appropriate or obtainable. Trade secrets are difficult to protect, and we have limited control over the protection of trade secrets used by our collaborators and suppliers. Although we use reasonable efforts to protect our trade secrets, our employees, consultants, contractors, outside scientific collaborators, and other advisors may unintentionally or willfully disclose our information to competitors. Enforcing a claim that a third party illegally obtained and is using any of our trade secrets is expensive and time consuming, and the outcome is unpredictable. In addition, state laws in the Unites States vary, and their courts as well as courts outside the United States are sometimes less willing to protect trade secrets. Moreover, our competitors may independently develop equivalent knowledge, methods, and know-how. If our confidential or proprietary information is divulged to or acquired by third parties, including our competitors, our competitive position in the marketplace will be harmed and our ability to successfully penetrate our target markets could be severely compromised.

We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.

As is common in the device, biotechnology and pharmaceutical industries, we employ individuals who were previously employed at other device, biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although no claims against us are currently pending, we may be subject to claims that these employees or we have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers. Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management, which would adversely affect our financial condition.

Litigation may be necessary to enforce or confirm the ownership of any patents issued or licensed to us, or to determine the scope and validity of third-party proprietary rights, which would result in substantial costs to us and diversion of effort on our part. If our competitors claim technology also claimed by us and prepare and file patent applications in the United States, we may have to participate in interference proceedings declared by the USPTO or a foreign patent office to determine priority of invention, which could result in substantial costs to and diversion of effort, even if the eventual outcome is favorable to us. Any such litigation or interference proceeding, regardless of outcome, could be expensive and time-consuming.

Successful challenges to our patents through oppositions, reexamination proceedings or interference proceedings could result in a loss of patent rights in the relevant jurisdiction. If we are unsuccessful in actions we bring against the patents of other parties, and it is determined that we infringe the patents of third-parties, we may be subject to litigation, prevented from commercializing potential products in the relevant jurisdiction and/or may be required to obtain licenses to those patents or develop or obtain alternative technologies, any of which could harm our business. Furthermore, if such challenges to our patent rights are not resolved in our favor, we could be delayed or prevented from entering into new collaborations or from commercializing certain products, which could adversely affect our business and results of operations.

Competitors or third parties may infringe on or upon our patents. We may be required to file patent infringement claims, which can be expensive and time-consuming. In addition, in an infringement proceeding, a court may decide that a patent of ours is not valid or is unenforceable or that the third party’s technology does not in fact infringe upon our patents. An adverse determination of any litigation or defense proceedings could put one or more of our patents at risk of being invalidated or interpreted narrowly and could put our related pending patent applications at risk of not issuing.

Litigation may fail and, even if successful, may result in substantial costs and be a distraction to our management. We may not be able to prevent misappropriation of our proprietary rights, particularly in countries outside the United States where patent rights may be more difficult to enforce. Further, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential or sensitive information could be compromised by disclosure in the event of litigation. In addition, during the course of litigation there could be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.

Some of our competitors may be able to sustain the costs of complex patent litigation more effectively than we can because they have substantially greater resources. In addition, any uncertainties resulting from the initiation and continuation of any litigation could have a material adverse effect on our ability to raise the funds necessary to continue our operations or otherwise have a material adverse effect on our business, results of operations, financial condition, and prospects.

5350

Table of Contents

Our commercial success will also depend, in part, on our ability to avoid infringing on patents issued by others. There may be issued patents of third parties of which we are currently unaware, that are infringed or are alleged to be infringed by our product candidate or proprietary technologies. Because some patent applications in the United States may be maintained in secrecy until the patents are issued, patent applications in the United States and many foreign jurisdictions are typically not published until eighteen months after filing, and publications in the scientific literature often lag behind actual discoveries, we cannot be certain that others have not filed patent applications for technology covered by our owned and in-licensed issued patents or our pending applications, or that we or, if applicable, a licensor were the first to invent the technology. Our competitors may have filed, and may in the future file, patent applications covering our product candidates or technology similar to ours. Any such patent application may have priority over our patent applications or patents, which could further require us to obtain rights to issued patents covering such technologies.

We may be exposed to, or threatened with, future litigation by third parties having patent or other intellectual property rights alleging that our product candidates and/or proprietary technologies infringe their intellectual property rights. These lawsuits are costly and could adversely affect our results of operations and divert the attention of managerial and technical personnel. There is a risk that a court would decide that we or our commercialization partners are infringing the third party’s patents and would order us or our partners to stop the activities covered by the patents. In addition, there is a risk that a court will order us or our partners to pay the other party damages for having violated the other party’s patents.

If a third-party’s patent were found to cover our product candidates, proprietary technologies or their uses, we could be enjoined by a court and required to pay damages and could be unable to commercialize our product candidates or use our proprietary technologies unless we or they obtained a license to the patent. A license may not be available to us on acceptable terms, if at all. In addition, during litigation, the patent holder could obtain a preliminary injunction or other equitable relief which could prohibit us from making, using or selling our product candidates, technologies or methods pending a trial on the merits, which could be years away.

Risks Relating to the ~~Issuances~~Issuance of Capital Stock, the Securities Markets and an Investment in ~~our~~Our Common Stock

Our stockholders may experience substantial dilution in the value of their investment if we issue additional shares of our capital stock.

Our certificate of incorporation allows us to issue up to ~~100~~2,000,000,000 shares of our common stock and to issue and designate the rights of, without stockholder approval, up to 5,000,000 shares of preferred stock.

Significant additional capital will be needed in the future to continue our planned operations, including further development of our product candidates, preparing IND or equivalent filings, conducting preclinical studies and clinical trials, commercialization efforts, expanded research and development activities and costs associated with operating a public company. To raise capital, we may sell common stock, convertible securities or other equity securities in one or more transactions at prices and in a manner we determine from time to time. If we sell common stock, convertible securities or other equity securities, investors may be materially diluted by subsequent sales. Such sales may also result in material dilution to our existing stockholders, and new investors could gain rights, preferences and privileges senior to the holders of our shares of common stock.

We may also issue additional shares of common stock or other equity securities of equal or senior rank in the future in connection with, among other things, future acquisitions or repayment of outstanding indebtedness, including without stockholder approval, in a number of circumstances. The issuance of additional shares or other equity securities of equal or senior rank would result in a decrease in existing stockholders’ proportionate ownership interest in us and the relative voting strength of each previously outstanding share of common stock, and may adversely affect the market price of our common stock.

Stockholders will suffer substantial additional dilution if certain provisions in the outstanding March 2025 Warrants are utilized.

On March 4, 2025, we entered into a securities purchase agreement (the “March 2025 Purchase Agreement”) with accredited investors, including certain of our existing stockholders, identified on the signature page thereto (collectively, the “March 2025 Private Placement Purchasers”) for a private placement of securities (the “March 2025 Private Placement”) for gross proceeds of approximately $15.0 million. Pursuant to the March 2025 Purchase Agreement, we issued an aggregate of 4,069,738 shares (the “March 2025 Private Placement Shares”) of our common stock and 23,972,400 Prefunded Warrants, with each March 2025 Private Placement Share or Prefunded Warrant accompanied by (i) a Series A common warrant (the “March 2025 Series A Warrants”) to purchase one share of common stock and (ii) one Series B common warrant (the “March 2025 Series B Warrants” and together with the March 2025 Series A Warrants, the “March 2025 Warrants”) to purchase one share of common stock.

Certain provisions in our outstanding March 2025 Warrants may result in significant dilution. The exercise price of the March 2025 Warrants will reset to a price equal to the greater of (i) the floor price of $0.132 (the “Floor Price”), and (ii) the lowest volume

weighted average price (“VWAP”) during a period commencing on the first trading day immediately following the later of (x) the earlier of (A) the first trading day after the initial registration statement that we are required to file to register the resale of the securities in the March 2025 Private Placement, or (B) the first trading day after the date on which the holder of those securities can sell them pursuant to Rule 144 under the Securities Act of 1933, as amended, without restriction or limitation, or (y) the first trading day after stockholder approval of certain provisions of the March 2025 Warrants is obtained, and the number of shares issuable upon exercise will be proportionately adjusted such that the aggregate exercise price will remain unchanged.

Subject to certain exceptions, if we sell any common stock (or securities convertible into or exercisable into common stock) at a price per share (or conversion or exercise price, as applicable) less than the exercise price of the March 2025 Series A Warrants then in effect, then the exercise price of the March 2025 Series A Warrants will be reduced to such lower price, but no lower than the Floor Price, and the number of shares issuable upon exercise will be proportionately adjusted such that the aggregate exercise price will remain unchanged.

Under the alternative cashless exercise option of the March 2025 Series B Warrant, a holder has the right to receive an aggregate number of shares equal to three times the aggregate number of shares of common stock that would be issuable upon a cash exercise of the March 2025 Series B Warrant, without any further payment to us.

Finally, if at any time there occurs any share split, share dividend, share combination recapitalization or other similar transaction involving our common stock and the lowest daily VWAP during the period commencing on the trading day immediately following the applicable date of share combination event and ending on the fifth trading day immediately following such date is less than the exercise price of the March 2025 Warrants then in effect, then the exercise price of the March 2025 Warrants will be reduced to the lowest daily VWAP during such period (subject to a minimum exercise price of the Floor Price), and the number of shares issuable upon exercise will be proportionately adjusted such that the aggregate exercise price will remain unchanged.

If any of the provisions described above are utilized, our stockholders would suffer substantial additional dilution.

As of March 21, 2025, we had 16,999,626 shares of common stock issued and outstanding. In addition, we had the March 2025 Warrants outstanding, as well as the Prefunded Warrants, Series A Warrants and Series B Warrants under the May 2024 Purchase Agreement, and 84,767 shares available for grant under our stock incentive plans. The issuance of shares upon exercise of our March 2025 Warrants, Prefunded Warrants, Series A Warrants and Series B Warrants under the May 2024 Purchase Agreement and options will cause immediate and substantial dilution to our stockholders and any sale thereof may depress the market price of our common stock.

The market price of our common stock may be volatile and fluctuate significantly, which could result in substantial losses for stockholders.

The market price of our common stock has been, and may continue to be, subject to significant fluctuations. Among the factors that may cause the market price of our common stock to fluctuate are the risks described in this “Risk Factors” section and other factors, including:

•

fluctuations in our operating results or the operating results of our competitors;

•

the outcome of clinical trials involving the use of our product candidates, including our sponsored trials;

•

changes in estimates of our financial results or recommendations by securities analysts;

•

variance in our financial performance from the expectations of securities analysts;

•

changes in the estimates of the future size and growth rate of our markets;

•

changes in accounting principles or changes in interpretations of existing principles, which could affect our financial results;

•

conditions and trends in the markets we currently serve or which we intend to target with our product candidates;

Table of Contents

•

changes in general economic, industry and market conditions;

•

success of competitive products and services;

•

changes in market valuations or earnings of our competitors;

•

announcements of significant new products, contracts, acquisitions or strategic alliances by us or our competitors;

•

our continuing ability to list our securities on an established market or exchange;

•

the timing and outcome of regulatory reviews and approvals of our product candidates;

•

the commencement or outcome of litigation involving our company, our general industry or both;

•

changes in our capital structure, such as future issuances of securities or the incurrence of additional debt;

•

actual or expected sales of our common stock by the holders of our common stock; and

•

the trading volume of our common stock.

In addition, the financial markets may experience a loss of investor confidence or otherwise experience continued volatility and deterioration. A loss of investor confidence may result in extreme price and volume fluctuations in our common stock that are unrelated or disproportionate to the operating performance of our business, our financial condition or results of operations, which may materially harm the market price of our common stock and result in substantial losses for stockholders. Further, although our common stock is traded on the Nasdaq, there is currently a limited market for our common stock and an active market may never develop. An active trading market in our common stock may not develop.

We may be or become the target of securities litigation, which is costly and time-consuming to defend.

In the past, following periods of market volatility in the price of a company’s securities, the reporting of unfavorable news or continued decline in a company’s stock price, security holders have often instituted class action litigation. The market value of our securities has steadily declined over the past several years for a variety of reasons discussed elsewhere in this “Risk Factors” section, which heightens our litigation risk. If we face such litigation, we could incur substantial legal costs and our management’s attention could be diverted from the operation of our business, causing our business to suffer. Any adverse determination in any such litigation or any amounts paid to settle any such actual or threatened litigation could require that we make significant payments.

In the future, we may attempt to increase our capital resources by entering into debt or debt-like financing that is unsecured or secured by up to all of our assets, or by issuing additional debt or equity securities, which could include issuances of secured or unsecured commercial paper, medium-term notes, senior notes, subordinated notes, guarantees, preferred stock, hybrid securities, or securities convertible into or exchangeable for equity securities. In the event of our liquidation, our lenders and holders of our debt and preferred securities would receive distributions of our available assets before distributions to the holders of our common stock. Because our decision to incur debt and issue securities in future offerings may be influenced by market conditions and other factors beyond our control, we cannot predict or estimate the amount, timing or nature of our future offerings or debt financings. Further, market conditions could require us to accept less favorable terms for the issuance of our securities in the future.

Our charter documents contain anti-takeover provisions.

Certain provisions of our amended and restated certificate of incorporation and amended and restated bylaws could discourage, delay or prevent a merger, acquisition or other change of control that stockholders may consider favorable. These provisions could also prevent or frustrate attempts by our stockholders to replace or remove members of our Board of Directors (the “Board”). Stockholders who wish to participate in these transactions may not have the opportunity to do so. These provisions:

•

authorize our Board to issue without stockholder approval up to 5,000,000 shares of preferred stock, the rights of which will be determined at the discretion of the Board;

•

require that stockholder actions must be effected at a duly called stockholder meeting and cannot be taken by written consent;

•

establish advance notice requirements for stockholder nominations to our Board or for stockholder proposals that can be acted on at stockholder meetings; and

•

limit who may call stockholder meetings.

We are governed by the provisions of Section 203 of the Delaware General Corporation Law, which may, unless certain criteria are met, prohibit large stockholders, in particular those owning 15% or more of the voting rights on our common stock, from merging or combining with us for a prescribed period of time.

5652

Table of Contents

We presently do not intend to pay cash dividends on our common stock.

We have never paid cash dividends in the past, and we currently anticipate that no cash dividends will be paid on the common stock in the foreseeable future. This could make an investment in our common stock inappropriate for some investors, and may serve to narrow our potential sources of additional capital. While our dividend policy will be based on the operating results and capital needs of the business, it is anticipated that all earnings, if any, will be retained to finance the future expansion of our business.

The trading market for our common stock may be influenced by the research and reports that industry or securities analysts publish about us or our business. If one or more of these analysts cease coverage of our company or fail to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline. In addition, it is likely that in some future period our operating results will be below the expectations of securities analysts or investors. If one or more of the analysts who cover us downgrade our stock, or if our results of operations do not meet their expectations, our stock price could decline.

General Risk Factors

Increased information technology security threats and more sophisticated and targeted computer crime could pose a risk to our systems, networks, and products.

Increased global information technology security threats and more sophisticated and targeted computer crime pose a risk to the security of our systems and networks and the confidentiality, availability and integrity of our data and communications. While we attempt to mitigate these risks by employing a number of measures, including employee refreshers, monitoring of our networks and systems, and maintenance of backup and protective systems, our systems, networks and products remain potentially vulnerable to advanced persistent threats. Depending on their nature and scope, such threats could potentially lead to the compromising of confidential information and communications, improper use of our systems and networks, manipulation and destruction of data, defective products, production downtimes and operational disruptions, which in turn could adversely affect our reputation, competitiveness and results of operations.

Item 1B. Unresolved Staff Comments

None.

Item 1C. Cybersecurity

Cybersecurity Program

We have implemented a cybersecurity program to support both the effectiveness of our systems and our preparedness for information security risks. This program includes a number of safeguards, such as: password protection; multi-factor authentication; monitoring and alerting systems for internal and external threats; and regular evaluations of our cybersecurity program.

We use a risk-based approach with respect to our use and oversight of third-party service providers, tailoring processes according to the nature and sensitivity of the data accessed, processed, or stored by such third-party service provider. We use a number of means to assess cyber risks related to our third-party service providers, including conducting due diligence in connection with onboarding new vendors. We also seek to include appropriate security terms in our contracts, where applicable as part of our oversight of third-party providers.

Process for Assessing, Identifying and Managing Material Risks from Cybersecurity Threats

We maintain an incident response program. In the event of a cybersecurity incident, designated personnel are responsible for assessing the severity of an incident and associated threat, containing the threat, remediating the threat, including recovery of data and access to systems, analyzing any reporting obligations associated with the incident, and performing post-incident analysis and program enhancements. We maintain a Data Breach Response Policy, which includes an Incident Response Plan (“IRP”) in the event of a significant cybersecurity incident. In the event of a significant cybersecurity incident, our Chief Financial Officer (“CFO”) will chair an incident response team to handle the incident. Such incident response team will include members of IT, finance (if applicable), legal, communications, human resources and any affected unit or department. IT, along with a designated forensic team, will use the IRP to guide the response.

Governance

Management Oversight

The controls and processes employed to assess, identify and manage material risks from cybersecurity threats are implemented and overseen by our Information Technology and Facilities Director (the “ITFD”). Our ITFD is a third-party consultant, from whom we have a dedicated resource who specializes in the industry and has over 25 years of experience addressing cybersecurity risks. Our ITFD is responsible for the day-to-day management of the cybersecurity program, including the prevention, detection, investigation, response to, and recovery from cybersecurity threats and incidents, and is regularly engaged to help ensure the cybersecurity program functions effectively in the face of evolving cybersecurity threats. Our CFO oversees the ITFD and briefs our Board on cybersecurity matters, including the nature and design of our cybersecurity program, and threats, events, and program enhancements.

Table of Contents

responsible for the day-to-day management of the cybersecurity program, including the prevention, detection, investigation, response to, and recovery from cybersecurity threats and incidents, and is regularly engaged to help ensure the cybersecurity program functions effectively in the face of evolving cybersecurity threats. Our CFO oversees the ITFD and briefs our Board on cybersecurity matters, including the nature and design of our cybersecurity program, and threats, events, and program enhancements.

Board Oversight

While the Board has overall responsibility for risk oversight, the Board delegated to the audit committee of the Board the responsibility for assisting the Board with cybersecurity disclosure matters. In its oversight role, the Board is expected to specifically consider risks that relate to the reputation of the Company and the general industry in which we operate, including with respect to privacy, information technology and cybersecurity and threats to technology infrastructure.

On a regular basis, the CFO reports to the Board on cybersecurity matters, including key risks, the potential impact of those exposures on the Company’s business, financial results, operations and reputation and the programs and steps implemented by management to monitor and mitigate risks.

Cybersecurity Risks

Our cybersecurity risk management processes are integrated into our overall approach to risk management. Given the nature and size of our Company, we do not have a dedicated enterprise risk function, but our executives regularly consider and evaluate risks to our Company. As part of that risk management process, members of our executive team identify, assess and evaluate risks impacting our operations across the Company, including those risks related to cybersecurity, and raise them for discussion with other executives, and where it is determined to be appropriate, issues are also raised to the Board for consideration.

As of the date of this report, we are not aware of any risks from cybersecurity threats, including as a result of any previous cybersecurity incidents, that have materially affected our business strategy, results of operations or financial condition or are reasonably likely to have such a material effect. While we have implemented a cybersecurity program, the techniques used to infiltrate information technology systems continue to evolve. Accordingly, we may not be able to timely detect threats or anticipate and implement adequate security measures. For additional information regarding risks relating to privacy and cybersecurity, see “Item 1A—Risk Factors.”

Item 2. Properties

Our corporate offices are in Houston, Texas. As of December 31, ~~2024~~2025, we had lease agreements for office space in Charlottesville, Virginia and ~~San Antonio~~Houston, Texas~~, which we vacated in February 2025, and paid an aggregate of approximately $16,000 in rent per month for these properties~~.

On October 16, 2025, we entered into a lease (the “Houston Lease”) with LG 1 Property Owner LP, pursuant to which we agreed to lease approximately 11,370 rentable square feet of space located at 6420 Levit Green Boulevard, Houston, Texas 77021. The Houston Lease is expected to commence on or about November 1, 2026. The Houston Lease provides for a monthly base rent of $58,745, which increases annually by approximately 3%, plus our share of the building’s direct expenses. The Houston Lease has an initial term of 120 calendar months.

Item 3. Legal Proceedings

None.

Item 4. Mine Safety Disclosures

Not applicable.

5854

Table of Contents

PART II

Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities

Market Prices

Market Information

The Company’s common stock is listed on the Nasdaq Capital Market under the symbol “PSTV.”

As of March 2110, ~~2025~~2026, the Company had approximately ~~seventeen~~25 record holders of common stock. Because many of the Company’s outstanding shares are held by brokers and other institutions on behalf of stockholders, the Company is unable to estimate the total number of individual stockholders represented by these record holders.

The Company has never paid cash dividends to its stockholders. The Company intends to retain future earnings for use in its business and does not anticipate paying cash dividends on its common stock in the foreseeable future. Any future dividend policy will be determined by the Board and will be based upon various factors, including the Company’s results of operations, financial condition, current and anticipated cash needs, future prospects, contractual restrictions and other factors as the Board may deem relevant.

~~Equity~~Purchases ~~Compensation~~of ~~Plan~~Equity ~~Information~~ Securities

The following table ~~gives~~provides certain information aswith ofrespect ~~December~~to ~~31,~~the ~~2024~~Company's ~~about~~purchases ~~shares~~ of ~~our~~its common stock ~~that~~for ~~may be issued upon~~ the ~~exercise~~three ofmonths ~~outstanding~~ended ~~options~~December 31, ~~and~~2025. ~~shares remaining available for issuance under all of our equity compensation plans:~~

Plan Category	Number of securities to be issued upon exercise of outstanding options, warrants and rights		Weighted-average exercise price of outstanding options, warrants and rights	Number of securities remaining available for future issuance under equity compensation plans (excluding securities reflected in column (a))
	Company Purchases of Common Stock
	(a)		(b)	(c)
Period	Total Number of Shares Purchased			Average Price Paid per Share		Total Number of Shares Purchased As Part of Publicly Announced Plans or Programs		Approximate Dollar Value of Shares That May Yet Be Purchased Under Plans or Programs(1)
Equity compensation plans approved by security holders (1)	23,897		$43.42	62,908
October 1 - 31, 2025		561,392		$	0.66		561,392	$	-
Equity compensation plans not approved by security holders (2)	574,643		$5.57	692,596
November 1 - 30, 2025		-		$	-		-	$	-
Total	598,540		$7.08	755,504
December 1 - 31, 2025		877,703		$	0.66		877,703	$	-
Total		1,439,095		$	0.66		1,439,095	$	-

(1)

~~Represents~~On March 4, 2025, the Company entered into a securities purchase agreement with various purchasers (ithe “Purchasers”), ~~options~~pursuant ~~outstanding~~to ~~that~~which ~~were~~the Company issued ~~under~~to ~~the~~such ~~2004~~Purchasers ~~Stock~~in ~~Option~~a ~~and~~private ~~Stock~~placement ~~Purchase~~(“March ~~Plan~~2025 ~~which~~Private ~~expired~~Placement”) incommon ~~August~~stock ~~2004~~of the Company. On June 17, 2025, the Company and the Purchasers entered into a letter agreement (iithe “Letter Agreement”) with each of the ~~2015~~Purchasers ~~New~~in ~~Employee~~an ~~Incentive~~effort ~~Plan~~to, among other items, minimize the dilutive impact of the March 2025 Private Placement. The Letter Agreement provided for the return and cancellation of Private Placement Shares and Pre-Funded Warrants. Refer to Note 15. Stockholders’ Equity in Part II of this Annual Report on Form 10-K for more information on the Letter Agreement.

See Notes to the Financial Statements included elsewhere herein for a description of our 2020 Stock Incentive Plan.

Item 6. [Reserved]

5955

Table of Contents

Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations

Our Management’s Discussion and Analysis of Financial Condition and Results of Operations includes the following sections:

•

Overview that discusses our business.

•

Results of Operations that includes a discussion of our revenue and expenses.

•

Liquidity and Capital Resources that discusses key aspects of our statements of cash flows, changes in our financial position and our financial commitments.

Overview

~~Our~~By ~~lead~~minimizing ~~radiotherapeutic~~radiation ~~candidate,~~exposure ~~REYOBIQ™ (rhenium~~to ~~(186Re)~~healthy ~~obisbemeda),~~tissues iswhile ~~designed~~simultaneously ~~specifically~~maximizing ~~for~~locoregional ~~CNS~~delivery ~~cancers~~and, ~~including recurrent glioblastoma (“GBM”)~~thereby, ~~leptomeningeal metastases (“LM”)~~efficacy, ~~and~~we ~~pediatric~~hope ~~brain~~to ~~cancers~~reduce ~~(“PBC”)~~the byradiation ~~direct~~toxicity ~~localized~~for ~~delivery~~patients, ~~utilizing~~improving ~~approved~~their ~~standard-~~quality of~~-care~~ ~~tissue~~life ~~access such as with convection-enhanced delivery (“CED”)~~ and ~~intraventricular~~life ~~brain (Ommaya reservoir) catheters~~expectancy. Our ~~acquired~~ radiotherapeutic ~~candidate~~platform, ~~Rhenium-188~~combined ~~NanoLiposome~~with ~~Biodegradable~~advances ~~Alginate~~in ~~Microsphere~~neurosurgery, ~~(“188RNL-BAM”)~~nuclear medicine, isinterventional ~~designed~~radiology, toneuro-oncology, ~~treat~~and ~~many~~radiation ~~solid~~oncology, ~~organ~~affords ~~cancers~~us ~~including~~the ~~primary~~opportunity ~~and~~to ~~secondary~~target ~~liver~~a ~~cancers~~broad byvariety ~~intra-arterial~~of ~~injection~~cancer types.

OnThe ~~April 26, 2024, we acquired all of the right, title and interest in a cerebrospinal fluid cancer diagnostic portfolio known as the~~ CNSide® ~~Platform~~Cerebrospinal ~~from~~Fluid ~~Biocept,~~Assay ~~Inc. (“Biocept”), which~~ is currently being utilized in the ReSPECT-LM clinical trial funded by the Cancer Prevention and Research Institute of Texas (“CPRIT”). In connection with our business plan for developing the CNSide™ Platform, we formed CNSide Diagnostics, ~~LLC (“CNSide Diagnostics”), a wholly owned subsidiary of the Company,~~ and our board of directors appointed a board of managers for CNSide Diagnostics. We ~~are~~re-introduced ~~planning for~~ the CNSide Cerebrospinal Fluid Tumor Cell Enumeration test (the “CNSide™ Test”), which is a laboratory developed test (“LDT”) in August 2025. The laboratory for the CNSide Test in Houston, toTexas behas ~~re-introduced~~received toa certificate of accreditation from the ~~U.S.~~Centers ~~market~~for ~~starting~~Medicare in& Medicaid Services (CMS) which deems the ~~second~~lab ~~quarter~~compliant ofwith ~~2025~~Clinical ~~after~~Laboratory weImprovement ~~complete~~Amendments a(“CLIA”) ~~number~~regulations. ofFurthermore, ~~steps~~CNSide ~~related~~Diagnostics has signed national agreements to ~~certifications,~~provide ~~state~~the ~~licensure,~~CNSide ~~payor~~Test ~~coverages~~with UnitedHealthcare Insurance Company and Humana, ~~reimbursement~~Inc. ~~codes~~effective September 15 and ~~financing~~October 29, 2025, respectively. These agreements expand access to more than 67 million covered lives across the United States.

InOur ~~March~~headquarters ~~2025,~~is welocated ~~moved~~in ~~our headquarters to~~ Houston, Texas, in proximity to world-class cancer institutions and researchers.

Pipeline

Our most advanced investigational drug, ~~REYOBIQ™~~rhenium (186Re) obisbemeda, is a patented radiotherapy potentially useful for patients with CNS and other cancers. WePreclinical ~~announced~~study indata ~~March~~describing ~~2025 that~~ the ~~U.S.~~use ~~Food~~of ~~and Drug Administration (“FDA”) conditionally accepted the proprietary name REYOBIQ™ to be used by us for~~ rhenium (186Re) obisbemeda. ~~Preclinical study data describing the use of REYOBIQ™~~ for several cancer targets have been published in peer-reviewed journals and reported at a variety of medical society peer-reviewed meetings. Besides GBM, LM and PBC, ~~REYOBIQ™~~rhenium (186Re) obisbemeda has been reported to have potential applications for head and neck cancer, ovarian cancer, breast cancer and peritoneal metastases.

The ~~REYOBIQ™~~rhenium (186Re) obisbemeda technology was part of a licensed radiotherapeutic portfolio that we acquired from NanoTx, Corp. (“NanoTx”) on May 7, 2020. The licensed radiotherapeutic has been evaluated in preclinical studies for several cancer targets and we have an active $3.0 million award from U.S. National Institutes of Health/National Cancer Institute which is expected to provide financial support for the continued clinical development of rhenium (186Re) obisbemeda for recurrent GBM through the completion of a Phase 2 clinical trial, including enrollment of up to 55 patients.

6056

~~the~~Table ~~continued clinical development~~ of ~~REYOBIQ™ for recurrent GBM through the completion of a Phase 2 clinical trial, including enrollment of up to 55 patients.~~ Contents

OnRhenium ~~August~~(186Re) ~~29,~~obisbemeda ~~2022,~~versus weExternal ~~announced~~Beam ~~feedback~~Radiation ~~from~~Therapy afor ~~Type~~Recurrent ~~C meeting with the FDA regarding Chemistry, Manufacturing and Controls practices.~~ GBM

~~The~~Rhenium ~~FDA~~(186Re) ~~indicated~~obisbemeda ~~agreement~~is ~~with~~a ~~our~~novel ~~proposed~~injectable ~~application~~radiotherapy ofdesigned ~~cGMP~~to ~~guidance~~deliver ~~for radiotherapeutics~~targeted, ~~small~~high ~~molecule~~dose ~~drug~~radiation ~~products~~directly ~~and~~into ~~liposome~~GBM ~~drug~~tumors ~~products for REYOBIQ™~~ in ~~support~~a ofsafe, ~~ongoing~~effective, and ~~future~~convenient ~~GBM~~manner ~~clinical~~that ~~trials,~~may ~~manufacturing~~ultimately ~~scale~~prolong ~~up,~~patient ~~and commercialization~~survival. ~~Alignment~~Rhenium ~~with~~(186Re) ~~the~~obisbemeda ~~FDA~~is ~~includes~~composed ~~support~~ of ~~our~~the ~~proposed~~radionuclide ~~controls~~Rhenium-186 and ~~release~~a ~~strategy~~nanoliposomal ~~for~~carrier, ~~new~~and ~~drug~~is ~~substance~~infused ~~and~~in ~~new~~a ~~drug~~highly ~~product.~~targeted, ~~Because~~controlled ~~this~~fashion, ~~product~~directly isinto ~~identical~~the ~~for~~tumor ~~recurrent~~via ~~GBM,~~precision ~~LM,~~brain mapping and ~~PBC,~~CED wecatheters. ~~believe~~Potential ~~alignment~~benefits ~~will~~of berhenium ~~consistent~~(186Re) ~~for~~obisbemeda ~~REYOBIQ™~~compared ~~used~~to instandard ~~other~~external ~~clinical~~beam ~~development~~radiotherapy ~~programs,~~or ~~including~~external LMbeam ~~and~~radiation ~~PBC.~~therapy (“EBRT”) include:

•

~~REYOBIQ™~~The ~~versus~~rhenium ~~External~~(186Re) ~~Beam~~obisbemeda ~~Radiation~~radiation ~~Therapy~~dose ~~for~~delivered ~~Recurrent~~to ~~GBM~~patients may be up to 20 times greater than what is possible with commonly used EBRT, which, unlike EBRT and proton beam devices, spares normal tissue and the brain from radiation exposure.

•

~~REYOBIQ™~~Rhenium is(186Re) aobisbemeda ~~novel~~can ~~injectable~~be ~~radiotherapy~~visualized ~~designed to deliver targeted, high dose radiation directly into GBM tumors~~ in areal-time ~~safe,~~during ~~effective~~administration, ~~and~~possibly ~~convenient~~giving ~~manner~~clinicians ~~that~~better ~~may~~control ~~ultimately prolong patient survival. REYOBIQ™ is composed~~ of ~~the~~radiation ~~radionuclide Rhenium-186 and a nanoliposomal carrier~~dosing, ~~and~~distribution ~~is infused in a highly targeted, controlled fashion, directly into the tumor via precision brain mapping~~ and ~~CED catheters~~retention. ~~Potential benefits of REYOBIQ™ compared to standard external beam radiotherapy or external beam radiation therapy (“EBRT”) include:~~

•

~~The~~Rhenium ~~REYOBIQ™~~(186Re) ~~radiation~~obisbemeda ~~dose~~potentially ~~delivered~~more toeffectively ~~patients~~treats ~~may~~a bebulk uptumor ~~to 20 times greater than what is possible with commonly used EBRT, which, unlike EBRT~~ and ~~proton~~microscopic ~~beam~~disease ~~devices,~~that ~~spares~~has ~~normal~~already ~~tissue~~invaded ~~and~~healthy ~~the brain from radiation exposure~~tissue.

•

~~REYOBIQ™~~Rhenium ~~can~~(186Re) beobisbemeda ~~visualized~~is ininfused ~~real-time~~directly ~~during~~into ~~administration~~the targeted tumor by CED catheter insertion using MRI guided software to avoid critical patient neurological structures and neural pathways and also bypasses the blood brain barrier, ~~possibly~~which ~~giving~~delivers ~~clinicians~~the ~~better~~therapeutic ~~control~~product ofwhere it is needed. Importantly, it reduces radiation ~~dosing~~exposure to healthy cells, ~~distribution~~in contrast to EBRT, which passes through normal tissue to reach the tumor, continuing its path through the tumor, hence being less targeted and ~~retention~~selective.

•

~~REYOBIQ™~~Rhenium ~~potentially~~(186Re) ~~more~~obisbemeda ~~effectively~~is ~~treats~~given during a ~~bulk~~single, ~~tumor~~short, in-patient hospital visit, and ~~microscopic~~is ~~disease~~available ~~that~~in ~~has~~all ~~already~~hospitals ~~invaded~~with ~~healthy~~nuclear ~~tissue~~medicine and neurosurgery, while EBRT requires out-patient visits five days a week for approximately four to six weeks.

REYOBIQ™ is infused directly into the targeted tumor by CED catheter insertion using MRI guided software to avoid critical patient neurological structures and neural pathways and also bypasses the blood brain barrier, which delivers the therapeutic product where it is needed. Importantly, it reduces radiation exposure to healthy cells, in contrast to EBRT, which passes through normal tissue to reach the tumor, continuing its path through the tumor, hence being less targeted and selective.

ReSPECT-GBM Trial for Recurrent GBM

While EBRT has been shown to be safe and has temporary efficacy in many malignancies including GBM, typically at absorbed, fractionated radiation dose of ~30 Gray in GBM, this maximum possible administered dose is always limited by toxicity to the normal tissues surrounding the malignancy and because EBRT requires fractionation to manage toxicity and maximum EBRT limits are typically reached before long-term efficacy reached. Because of this limitation, EBRT cannot provide a cure or long-term control of GBM and GBM always recurs within months after EBRT. In contrast, locally delivered and targeted radiopharmaceuticals that precisely deliver radiation in the form of beta particles such as Iodine-131 for thyroid cancer, are known to be safe and effective and minimize exposure to normal cells and tissues especially with optimal administered dose and minimizing exposure to normal tissue. The locally delivered ~~REYOBIQ™~~rhenium (186Re) obisbemeda is designed for and provides patient tolerability and safety. Though no ~~REYOBIQ™~~rhenium (186Re) obisbemeda head-to-head trial with chemo, immune, EBRT or systemic radiopharmaceutical products have been conducted, patient tolerability and safety considerations have been reported as expected.

61In September 2020, the FDA granted both orphan drug designation and Fast Track designations to rhenium (186Re) obisbemeda for the treatment of patients with GBM.

~~chemo~~Rhenium (186Re) obisbemeda is under clinical investigation in a Phase 1/2 multicenter, ~~immune~~sequential cohort, ~~EBRT~~open-label, orvolume ~~systemic~~and ~~radiopharmaceutical~~dose ~~products~~escalation ~~have~~study ~~been~~(“ReSPECT-GBM”) ~~conducted,~~of ~~patient~~the safety, tolerability, and ~~safety~~distribution ~~considerations~~of ~~have~~rhenium ~~been~~(186Re) ~~reported~~obisbemeda asgiven ~~expected~~by CED catheters to patients with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment. The trial is funded through Phase 2 in large part by a National Institute of Health/National Cancer Institute grant.

InWe ~~September~~completed ~~2020,~~Phase ~~the~~1 ~~FDA~~of ~~granted~~our ~~both~~ReSPECT-GBM ~~orphan~~Trial ~~drug~~and ~~designation~~are ~~and~~targeting ~~Fast~~full ~~Track~~enrollment ~~designations~~into toPhase ~~REYOBIQ™~~2 ~~for~~by the ~~treatment~~end of ~~patients with GBM~~2026.

REYOBIQ™ is under clinical investigation in a Phase 1/2 multicenter, sequential cohort, open-label, volume and dose escalation study (“ReSPECT-GBM”) of the safety, tolerability, and distribution of REYOBIQ™ given by CED catheters to patients with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment. The trial is funded through Phase 2 in large part by a National Institute of Health/National Cancer Institute grant.

Filing Compare · PLUS THERAPEUTICS, INC.