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What changed in PLUS THERAPEUTICS, INC.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of PLUS THERAPEUTICS, INC.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+567 added−575 removedSource: 10-K (2026-03-12) vs 10-K (2025-03-31)

Top changes in PLUS THERAPEUTICS, INC.'s 2025 10-K

567 paragraphs added · 575 removed · 340 edited across 6 sections

Item 1. Business

Business — how the company describes what it does

132 edited+55 added−124 removed160 unchanged
Biggest changeWe 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.
Biggest changeIntellectual 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.
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.
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, maximum EBRT limits are typically reached before long-term efficacy is reached.
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; • 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.
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.
Once 11 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.
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.
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.
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.
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 • a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.
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 21 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.
Moreover, after clearance or approval is given, if the product is shown to be hazardous or defective, the FDA has the power to withdraw the clearance 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.
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.
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 application.
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 that subsequent application.
A requestor may submit a de novo request for classification after receiving a “not substantially 21 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.
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.
In this instance, the three-year exclusivity period does not preclude 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.
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.
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.
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.
Any reduction in reimbursement from Medicare or other government programs may result in a similar 25 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.
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.
The FDA and other agencies actively enforce the laws and regulations prohibiting the 22 promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability, including substantial monetary penalties and criminal prosecution.
The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability, including substantial monetary penalties and criminal prosecution.
This requirement applies 19 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.
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.
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.
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.
Investigators and IRBs must also comply with FDA regulations and guidelines, including those regarding oversight of study patient 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.
Investigators and IRBs must also comply with FDA regulations and guidelines, including those regarding oversight of study 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.
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 to assess the characteristics and potential safety and efficacy of the product candidate.
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 studies to assess the characteristics and potential safety and efficacy of the product candidate.
Device Modifications post-clearance or approval Medical devices can be marketed only for the indications for which they are cleared or approved.
Device Modifications post-clearance or approval Medical devices can be marketed only for the indications for which they are cleared, authorized or approved.
In 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.
In 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, authorized or cleared by the FDA may not be promoted for unapproved, unauthorized or uncleared uses, otherwise known as “off-label” promotion.
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 20 unapproved uses, industry-sponsored scientific and educational activities and promotional activities involving the internet.
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.
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, 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.
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 10 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.
By minimizing radiation exposure to healthy tissues while simultaneously maximizing locoregional delivery and, thereby, efficacy, we hope to reduce the radiation toxicity for patients, improving their quality of life and life expectancy. Our radiotherapeutic platform, combined with advances in surgery, nuclear medicine, interventional radiology, and radiation oncology, affords us the opportunity to target a broad variety of cancer types.
By minimizing radiation exposure to healthy tissues while simultaneously maximizing locoregional delivery and, thereby, efficacy, we hope to reduce the radiation toxicity for patients, improving their quality of life and life expectancy. Our radiotherapeutic platform, combined with advances in neurosurgery, nuclear medicine, interventional radiology, neuro-oncology, and radiation oncology, affords us the opportunity to target a broad variety of cancer types.
If criteria are not met for Priority Review, the standard FDA review period is ten months from FDA filing or 12 months from sponsor submission. Priority Review designation does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval.
If criteria are not met for Priority Review, the standard FDA review period is ten months from FDA filing or 12 months from NDA submission. Priority Review designation does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval.
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.
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, 9 Table of Contents develop, commercialize and otherwise exploit certain patents, know-how and technology related to the development of radiolabeled nanoliposomes.
In addition, if a product receives the first FDA approval for the indication 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.
In addition, if a product receives the first FDA approval for the 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.
After completion of the required clinical testing, a drug product 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.
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 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 recall the modified device until a new 510(k) clearance or PMA approval is obtained.
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.
ReSPECT-LM Clinical Trials for LM 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.
ReSPECT-LM Clinical Trials for LM 6 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.
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.
Pediatric Information Under the Pediatric Research Equity Act (“PREA”), certain NDAs must include an assessment, based on clinical data, of the safety and effectiveness of the product candidate in relevant pediatric populations.
Companies engaged in manufacturing drug products or their components 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.
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.
Manufacturers that fail to pay refunds could be subject to civil monetary penalties of 125 percent of the refund amount. 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.
Manufacturers that fail to pay refunds could be subject to civil monetary penalties of 125 percent of the refund amount. 22 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.
It is a rare disease with increasing U.S. annual incidence (42,000) and deaths (30,000). The FDA has informed us that 188 RNL-BAM will be regulated as a medical device under the Federal Food, Drug, and Cosmetic Act (the “FDCA”).
It is a rare disease with increasing U.S. annual incidence (42,000) and deaths (30,000). Subsequently, the FDA has informed us that 188 RNL-BAM will be regulated as a medical device under the Federal Food, Drug, and Cometic Act (“FDCA”).
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 16 conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients.
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 conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial participants.
Changes that could require a new marketing application 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 is generally linked to the classification of the device.
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.
Each protocol involving testing on U.S. patients 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.
Each protocol involving testing on U.S. 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.
Pharmaceutical Product Approval 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; 15 • 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 of safety and 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 completion of an FDA Advisory Committee review, if applicable; • Potential FDA audit of the preclinical and clinical trial sites that generated the data in support of the NDA; 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.
Pharmaceutical Product Approval 12 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 evidence that 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; • Potential FDA audit of the preclinical and clinical trial sites that generated the data in support of the NDA; • Satisfactory completion of FDA inspections 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.
Our lead radiotherapeutic candidate, REYOBIQ™ (rhenium ( 186 Re) obisbemeda), is designed specifically for CNS cancers including recurrent glioblastoma (“GBM”), leptomeningeal metastases (“LM”), and pediatric brain cancers (“PBC”) by direct localized delivery utilizing approved standard-of-care tissue access such as with convection-enhanced delivery (“CED”) and intraventricular brain (Ommaya reservoir) catheters.
In radiopharmaceuticals, our lead candidate, rhenium ( 186 Re) obisbemeda, is designed specifically for CNS cancers including recurrent glioblastoma (“GBM”), leptomeningeal metastases (“LM”), and pediatric brain cancers (“PBC”) by direct localized delivery utilizing approved standard-of-care tissue access such as with convection-enhanced delivery (“CED”) and intraventricular brain (Ommaya reservoir) catheters.
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™ 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.
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. • Rhenium ( 186 Re) obisbemeda 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.
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.
The study concluded that the technology required for radiolabeling BAM could successfully deliver, embolize and retain radiation in the target organ. 188 RNL-BAM is a preclinical investigational device we intend to further develop and move into clinical trials.
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.
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 14 Table of Contents new NDA or NDA supplement before the change can be implemented.
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 allowable patent term extension is calculated as one half of the 16 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.
Potential benefits of REYOBIQ™ compared to standard external beam radiotherapy or external beam radiation therapy (“EBRT”) include: • The REYOBIQ™ radiation dose delivered to 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™ can be visualized in real-time during administration, possibly giving clinicians better control of radiation dosing, distribution and retention. • REYOBIQ™ potentially more effectively treats a bulk tumor and microscopic disease that has already invaded healthy tissue. • 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.
Potential benefits of rhenium ( 186 Re) obisbemeda compared to standard external beam radiotherapy or external beam radiation therapy (“EBRT”) include: • The rhenium ( 186 Re) obisbemeda radiation dose delivered to 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. • Rhenium ( 186 Re) obisbemeda can be visualized in real-time during administration, possibly giving clinicians better control of radiation dosing, distribution and retention. • Rhenium ( 186 Re) obisbemeda is designed to effectively treat a bulk tumor and microscopic disease that has already invaded healthy tissue. • Rhenium ( 186 Re) obisbemeda 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.
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 REYOBIQ™ 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.
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 ( 186 Re) 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.
Other U.S. Healthcare Laws and Compliance Requirements In the United States, our activities 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.
Other U.S. Healthcare Laws and Compliance Requirements In the United States, 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.
The processes for obtaining regulatory 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.
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.
These fees are typically increased annually. The FDA has 60 days from its receipt of an NDA to determine whether the application will be accepted for filing based on the agency’s threshold determination that it is sufficiently complete to permit substantive review.
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.
Besides GBM, LM and PBC, REYOBIQ™ has been reported to have potential applications for head and neck cancer, ovarian cancer, breast cancer and peritoneal metastases. The REYOBIQ™ technology was part of a licensed radiotherapeutic portfolio that we acquired from NanoTx, Corp. (“NanoTx”) on May 7, 2020.
Besides GBM, LM and PBC, rhenium ( 186 Re) obisbemeda has been reported to have potential applications for head and neck cancer, ovarian cancer, breast cancer and peritoneal metastases. The rhenium ( 186 Re) obisbemeda technology was part of a licensed radiotherapeutic portfolio that we acquired from NanoTx, Corp. (“NanoTx”) on May 7, 2020.
REYOBIQ™ is an 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. All patients have shown well tolerated prompt and durable REYOBIQ™ distribution throughout the subarachnoid space.
Rhenium ( 186 Re) obisbemeda is an 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. All patients have shown well tolerated prompt and durable rhenium ( 186 Re) obisbemeda distribution throughout the subarachnoid space.
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 that the device is safe and effective for its intended use(s).
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 establish a reasonable assurance that the device is safe and effective for its intended use(s).
If the FDA determines that the NDA or IND is a rare pediatric disease product application, and if the NDA or IND is approved, the FDA will award the sponsor of the NDA or IND a voucher upon approval of the NDA or IND.
If the FDA determines that the NDA or BLA is a rare pediatric disease product application, and if the NDA or BLA is approved or licensed, the FDA will award the sponsor of the NDA or BLA a voucher upon approval of the NDA or BLA.
De Novo Classification Process 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.
De Novo Classification Process 18 Table 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.
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™ administered through intrathecal infusion to the ventricle of patients with LM after standard surgical, radiation, and/or chemotherapy treatment.
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 rhenium ( 186 Re) obisbemeda administered through intrathecal infusion to the ventricle of patients with LM after standard surgical, radiation, and/or chemotherapy treatment.
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 8 with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment.
Rhenium ( 186 Re) 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 rhenium ( 186 Re) obisbemeda given by CED catheters to patients with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment.
Competition for our product candidate, particularly REYOBIQ™ and 188 RNL-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.
Competition for our product candidate, particularly rhenium ( 186 Re) obisbemeda and 188 RNL-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.
Upon receiving acceptance of our Investigational New Drug application and Fast Track designation by the FDA for REYOBIQ™ 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.
Upon receiving acceptance of our Investigational New Drug application and Fast Track designation by the FDA for rhenium ( 186 Re) 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.
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.
A new IND submission was made in 2023. 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.
The locally delivered REYOBIQ™ is designed for and provides patient tolerability and safety. Though no REYOBIQ™ 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.
The locally delivered rhenium ( 186 Re) obisbemeda is designed for and provides patient tolerability and safety. Though no rhenium ( 186 Re) 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.
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.
Specifically, in 2022 we transferred the 188 RNL-BAM technology from UTHSCSA, and began planning to develop the product and complete early preclinical studies to support a future 8 Table of Contents FDA IND submission. Our intended initial clinical target is liver cancer which is the sixth most common and third deadliest cancer worldwide.
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 System Regulation (QSR), facility registration and device listing, reporting of adverse events and malfunctions, which is referred to as medical device reporting, and truthful and non-misleading labeling and promotional materials.
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 (“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.
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.
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.
The ReSPECT-LM Phase 1 clinical trial was preceded with preclinical studies in which tolerance to doses of REYOBIQ™ 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.
The ReSPECT-LM Phase 1 clinical trial (ClinicalTrials.gov NCT05034497) was preceded by preclinical studies in which tolerance to doses of rhenium ( 186 Re) 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.
In addition, the manufacturer of an investigational drug in a Phase 2 or Phase 3 clinical trial for a serious disease or condition is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for expanded access to such investigational drug.
In addition, the manufacturer of an investigational drug in a Phase 2 or Phase 3 clinical trial for a serious disease or condition, or of an investigational drug that has received Fast Track designation or Breakthrough Therapy designation, is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for expanded access to such investigational drug.
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, 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.
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.
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 for filing any ANDA or 505(b)(2) application for a drug with the same active moiety.
If such a product is a new chemical entity (“NCE”), 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 receive or file any ANDA or 505(b)(2) application for a drug with the same active moiety.
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.
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. 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, 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.
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.
A new medical device could either be a device that has not previously received marketing authorization in the US, or a previously authorized device that has been changed in such a way that would require a new marketing application.
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 submission.
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.
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.
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. 14 • A U.S. patent directed to a microarray for assaying for target material in a biological sample.
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 microflow apparatus.
(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 requirements, except for the QSR’s complaint handling and recordkeeping requirements.
(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 QMSR requirements, except for the QMSR’s requirements relating to records and complaint files.
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.
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.
Item 1. B usiness 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 company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (“CNS”) cancers.
Item 1. B usiness 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. healthcare company developing and commercializing precision diagnostics and targeted radiopharmaceuticals for central nervous system (“CNS”) cancers.
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 do FDA’s requirements to obtain market authorization.
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 does FDA’s requirements for premarket review.
Manufacturing sites are subject to periodic inspection by the FDA for compliance with the FDA's Quality System Regulations, which cover the procedures and documentation of the design, testing, production, control, quality assurance, labeling, packaging, sterilization, storage and shipping of medical devices; the Medical Device Reporting regulation, which requires that manufacturers report to the FDA if a device they manufactured 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.
Medical device establishments are subject to periodic inspection by the FDA for compliance with applicable FDA regulatory requirements, including the FDA's QMSR, which covers, among 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 and 19 Table of Contents importers 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.
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 Reed Road, Suite 160, Houston, TX 77051. Our telephone number is (737) 255-7194.
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 6420 Levit Green Boulevard, Suite 210, Houston, TX 77021. Our telephone number is (737) 255-7194.
Our novel radioactive drug formulations and medical devices and therapeutic candidates are designed to deliver safe and effective doses of radiation to tumors. To achieve this, we have developed innovative approaches to drug formulation, including encapsulating radionuclides such as rhenium isotopes with nanoliposomes and microspheres.
Our novel radioactive drug formulations, medical devices and therapeutic candidates have the potential to overcome these disadvantages as they are designed to deliver safe and effective doses of radiation at the tumors—potentially in a single treatment. To achieve this, we have developed innovative approaches to drug formulation, including encapsulating radionuclides such as rhenium isotopes with nanoliposomes and microspheres.
As of December 31, 2024, we had received approximately $10.4 million in milestone payments under the CPRIT Contract. Interim results showed that a single treatment with REYOBIQ™ resulted in a consistent decreased cerebrospinal fluid (“CSF”) tumor cell count/ml and was tolerated by all LM patients.
As of December 31, 2025, we had received approximately $15.9 million in milestone payments under the CPRIT Contract. Interim results showed that a single treatment with rhenium ( 186 Re) obisbemeda resulted in a consistent decreased cerebrospinal fluid (“CSF”) circulating tumor cell (“CTC”) count/ml and was tolerated by all LM patients.
(“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.
The CNSide Cerebrospinal Fluid Assay 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 and our board of directors appointed a board of managers for CNSide Diagnostics.
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. 23 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.
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 20 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.
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. Once the submission is accepted for filing, the FDA begins an in-depth 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.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeFailure 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. 43 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.
Biggest changeWe, 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. 38 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.
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; 30 • 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 CNSide TM Portfolio.
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 CNSide TM Portfolio.
There can be no assurance that we would obtain sufficient capital to fund the development, manufacturing, and commercialization of our nanomedicine program ourselves, 34 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. 188 RNL-BAM will be regulated as a medical device, which may result in additional regulatory and other risks. 188 RNL-BAM was developed and tested preclinically as a drug product.
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. 188 RNL-BAM will be regulated as a medical device, which may result in additional regulatory and other risks. 188 RNL-BAM was developed and tested preclinically as a drug product.
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, 37 in the event we violate certain covenants pertaining to various matters that include any potential relocation outside of the State of Texas.
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.
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 or clearances of future or pending product submissions, fines, recalls, import or seizures of products, total or partial suspensions of production and criminal prosecution.
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.
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, or clearance from the FDA or achieve commercialization earlier than we can, any of which could have a substantial negative effect on our business.
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.
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, 49 or transmit protected health information in connection with providing a specified service or performing a function on behalf of a covered entity.
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.
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. 33 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.
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.
Delays in receipt of or failure to receive such approvals or clearances, or the loss of previously received approvals 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.
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.
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 CNSide TM Test to patients. In order to be commercially viable, clinical lab tests must be covered and reimbursed by third party payers.
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 CNSide Test to patients. In order to be commercially viable, clinical lab tests must be covered and reimbursed by third party payers.
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. Our common stock is currently listed on The Nasdaq Capital Market.
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. Our common stock is currently listed on The Nasdaq Capital Market.
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 42 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.
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.
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 46 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.
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 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 48 highly complex process that requires significant experience and know-how.
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.
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 41 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.
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.
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 40 terms of clinical and commercial success.
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 our competitors offer a clinical lab test that competes with our CNSide TM 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.
If our competitors offer a clinical lab test that competes with our 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.
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; • 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 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; 39 • 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).
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; 34 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; • 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 are not permitted to market our product candidates in the United States until we receive approval from the FDA, or in any foreign countries until we receive the requisite approval from the regulatory authorities of such countries (including centralized marketing authorization from the European Commission), and we may never receive such regulatory approvals.
We are not permitted to market our product candidates in the United States until we receive clearance, authorization or approval from the FDA, or in any foreign countries until we receive the requisite clearance, authorization or approval from the regulatory authorities of such countries (including centralized marketing authorization from the European Commission), and we may never receive such regulatory clearance, authorization or approvals.
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.
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.
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.
We may in the future discover 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.
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 CNSide TM Portfolio, and we may not be successful in our efforts to develop, fully utilize and monetize it.
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 CNSide Portfolio, and we may not be successful in our efforts to develop, fully utilize and monetize it.
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 CNSide TM Test.
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 CNSide Test.
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 47 nature of our products and product candidates.
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.
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; • 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.
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; 36 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.
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; • 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; 55 • 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.
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; 51 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.
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; • 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.
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; 37 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.
There can be no assurance that after such occurrences that we will be able to obtain additional necessary regulatory approvals or clearances on a timely basis, if at all.
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.
In April 2024, we completed the acquisition of substantially all of the right, title and interest in CNSide TM , including the CNSide Test, which is designed to detect, quantify, and monitor tumor status in LM.
In April 2024, we completed the acquisition of substantially all of the right, title and interest in CNSide, including the CNSide Test, which is designed to detect, quantify, and monitor tumor status in LM.
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; • 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.
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; 32 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.
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; • 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.
We may be unable to identify, hire and retain personnel with the requisite experience to conduct the operations necessary to obtain regulatory clearance, authorization or approval and commercialize our RNL product candidates, in which case our business would be materially harmed; • 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.
We are currently evaluating and developing our business plan for developing the CNSide TM diagnostic portfolio alongside our lead radio therapeutic candidate, rhenium ( 186 Re) obisbemeda, and seeking partnering opportunities for CNSide TM but there can be no assurances that we will be able to develop the technology to allow 50 for commercial applications, or successfully utilize and fully integrate CNSide TM into our operations.
We are currently evaluating and developing our business plan for developing the CNSide diagnostic portfolio alongside our lead radio therapeutic candidate, rhenium ( 186 Re) obisbemeda, and seeking partnering opportunities for 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.
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™ and 188 RNL-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.
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 rhenium ( 186 Re) obisbemeda and 188 RNL-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.
Compliance with the FDCA for a medical device includes, among other things, registration and listing, quality system regulations, and premarket authorization.
Compliance with the FDCA for a medical device includes, among other things, registration and listing, quality management system regulations, and premarket authorization.
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.
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.
We may not generate revenues from or realize the anticipated benefits of CNSide TM within our expected timeline or at all.
We may not generate revenues from or realize the anticipated benefits of CNSide within our expected timeline or at all.
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 or other requirements and request, or seek remedial action.
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 the QMSRs or other requirements and request, or seek remedial action.
For example: 51 • we, NanoTx, or UTHSCSA, as the case may be, might not have been the first to file patent applications for REYOBIQ™ or 188 RNL-BAM; • we, or Biocept, as the case may be, might not have been the first to file patent applications for the CNSide TM 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™ or 188 RNL-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™ or 188 RNL-BAM; • the API used in REYOBIQ™, 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.
For example: 48 Table of Contents • we, NanoTx, or UTHSCSA, as the case may be, might not have been the first to file patent applications for rhenium ( 186 Re) obisbemeda or 188 RNL-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 rhenium ( 186 Re) obisbemeda or 188 RNL-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 rhenium ( 186 Re) obisbemeda or 188 RNL-BAM; • the API used in rhenium ( 186 Re) 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.
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 as we perform clinical trials and other development activities for our nanomedicine product candidates.
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, 2026 as we perform clinical trials and other development activities for our nanomedicine product candidates.
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.
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.
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.
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.
The product candidates we currently have under development will require significant development, pre-clinical 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.
The product candidates we currently have under development will require significant development, 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.
Pre-clinical 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.
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 has informed us that 188 RNL-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 or premarket approval (“PMA”), from the FDA, unless an exemption applies.
The FDA has informed us that 188 RNL-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.
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.
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.
One or more of our competitors may develop other products that compete with ours, obtain necessary approvals for such products from the FDA, the European Commission, Ministry of Health, Labour and Welfare or other agencies, if required, more 38 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.
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 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.
The manufacturing preference requirement can be waived 42 Table of 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.
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.
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 33 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.
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. 53 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.
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. 50 Table of Contents 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.
Any failure to obtain regulatory approval of any of our product candidates would limit our ability 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.
Any failure to obtain regulatory clearance, authorization or approval of any of our product candidates would limit our ability to generate future revenue (and any failure to obtain such clearance, authorization or 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.
Risks Relating to the Issuances 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.
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.
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. 56 We presently do not intend to pay cash dividends on our common stock.
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. 52 Table of Contents We presently do not intend to pay cash dividends on our common stock.
If a product candidate is not 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 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.
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.
Even if we successfully obtain regulatory 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 approval.
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.
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.
Furthermore, if we experience 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 certificate of incorporation allows us to issue up to 100,000,000 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.
Our certificate of incorporation allows us to issue up to 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.
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.
Furthermore, we also could be required to seek funds through 26 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.
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.
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.
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 Federal Trade Commission ("FTC") also sets expectations for taking appropriate steps to safeguard consumers' personal information, and providing a level 46 Table of Contents of privacy or security commensurate to promises made to individuals.
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.
As 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.
If payers fail to cover the test, impose restrictions on the scope of coverage, or do not provide sufficient reimbursement for the CNSide TM 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.
If payers fail to cover the test, impose restrictions on the scope of 47 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.
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”), as well as equivalent requirements and inspections by state and foreign. regulatory authorities.
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 QMSR, as well as equivalent requirements and inspections by state and foreign. regulatory authorities.
This market exclusivity does not, however, pertain to indications other than those for which the drug is 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.
This market exclusivity does not, however, block 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.
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.
Under the license agreement with NanoTx, we are required to use commercial reasonable efforts to develop the rhenium ( 186 Re) 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.
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. 36 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™.
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. 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, rhenium ( 186 Re) obisbemeda.
For example, REYOBIQ™ and 188 RNL-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.
For example, rhenium ( 186 Re) obisbemeda and 188 RNL-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.
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™ and 188 RNL-BAM, and our CNSide TM Platform, as well as successfully defending our intellectual property against third-party challenges.
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 rhenium ( 186 Re) obisbemeda and 188 RNL-BAM, and our CNSide Platform, as well as successfully defending our intellectual property against third-party challenges.
We may incur significant costs in complying with environmental laws, rules and regulations. We recently acquired the CNSide TM diagnostic portfolio, and we may not be successful in our efforts to develop, fully utilize and monetize it.
We may incur significant costs in complying with environmental laws, rules and regulations. We may not be successful in our efforts to develop, fully utilize and monetize the CNSide diagnostic portfolio.
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. 52 We may not be able to protect our trade secrets.
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.
Our ability to successfully develop and commercialize REYOBIQ™ and 188 RNL-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.
Our ability to successfully develop and commercialize rhenium ( 186 Re) obisbemeda and 188 RNL-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 29 Table of Contents expertise necessary to develop, manufacture, and commercialize our nanomedicine product candidates.
In addition, a PMA generally requires 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 approvals could harm our business.
In addition, a PMA and a de novo generally 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.
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.
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.
Our future success is in large part dependent upon our ability to successfully develop our nanomedicine platform and commercialize REYOBIQ™ and 188 RNL-BAM and any failure to do so could significantly harm our business and prospects.
Our future success is in large part dependent upon our ability to successfully develop our nanomedicine platform and commercialize rhenium ( 186 Re) obisbemeda and 188 RNL-BAM and any failure to do so could significantly harm our business and prospects.
Obtaining regulatory approval for a product candidate is a lengthy, expensive and uncertain process, and may not be obtained.
Obtaining regulatory clearance, authorization or approval for a product candidate is a lengthy, expensive and uncertain process, and may not be obtained.
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.
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.
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; • 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.
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 • it is possible that the new legislation in our priority markets will yield additional regulatory requirements for therapeutic drugs for our nanomedicine product candidates.
Furthermore, even if we are granted regulatory approvals, they may include significant limitations on the approved and labeled indications for use for the device, which may limit the market for the device.
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 the process of obtaining either premarket clearance 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 , or that it is safe and effective for its intended use, based, in part, on extensive data, including, but not limited to, technical, preclinical, clinical, manufacturing and labeling data.
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 has a reasonable assurance of safety and effectiveness for its intended use, based, in part, on extensive data, which may include, but is not limited to, technical, preclinical, clinical, manufacturing and labeling data.
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.
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.
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. Product development involves a lengthy and expensive process, with an uncertain outcome.
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.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeOur 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.
Biggest changeGovernance 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 incident s, and is regularly engaged to help ensure the cybersecurity program functions effectively in the face of evolving cybersecurity threats.
Our ITFD is 53 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 incident s, and is regularly engaged to help ensure the cybersecurity program functions effectively in the face of evolving cybersecurity threats.
Such incident response team will include members of IT, finance (if applicable), legal, communications, human resources and any affected unit or department.
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.
Removed
IT, along with a designated forensic team, will use the IRP to guide the response. 57 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”).

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeItem 2. Pr operties Our corporate offices are in Houston, Texas. As of December 31, 2024, we had lease agreements for office space in Charlottesville, Virginia and San Antonio, Texas, which we vacated in February 2025, and paid an aggregate of approximately $16,000 in rent per month for these properties. Item 3. Legal Proceedings None. Item 4.
Biggest changeItem 2. Pr operties Our corporate offices are in Houston, Texas. As of December 31, 2025, we had lease agreements for office space in Charlottesville, Virginia and Houston, Texas.
Removed
Mine Saf ety Disclosures Not applicable. 58 PART II
Added
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.
Added
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 Saf ety Disclosures Not applicable. 54 Table of Contents PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

1 edited+4 added−2 removed3 unchanged
Biggest changeItem 5. Market for Registrant’s Common Equity, Related Sto ckholder 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 21, 2025, the Company had approximately seventeen record holders of common stock.
Biggest changeItem 5. Market for Registrant’s Common Equity, Related Sto ckholder 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 10, 2026, the Company had approximately 25 record holders of common stock.
Removed
Equity Compensation Plan Information The following table gives information as of December 31, 2024 about shares of our common stock that may be issued upon the exercise of outstanding options, and 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)) (a) (b) (c) Equity compensation plans approved by security holders (1) 23,897 $43.42 62,908 Equity compensation plans not approved by security holders (2) 574,643 $5.57 692,596 Total 598,540 $7.08 755,504 1.
Added
Purchases of Equity Securities The following table provides certain information with respect to the Company's purchases of its common stock for the three months ended December 31, 2025.
Removed
Represents (i) options outstanding that were issued under the 2004 Stock Option and Stock Purchase Plan which expired in August 2004 and (ii) the 2015 New Employee Incentive Plan. 2. See Notes to the Financial Statements included elsewhere herein for a description of our 2020 Stock Incentive Plan. Item 6. [Reserved] 59
Added
Company Purchases of Common Stock 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) October 1 - 31, 2025 561,392 $ 0.66 561,392 $ - November 1 - 30, 2025 - $ - - $ - December 1 - 31, 2025 877,703 $ 0.66 877,703 $ - Total 1,439,095 $ 0.66 1,439,095 $ - (1) On March 4, 2025, the Company entered into a securities purchase agreement with various purchasers (the “Purchasers”), pursuant to which the Company issued to such Purchasers in a private placement (“March 2025 Private Placement”) common stock of the Company.
Added
On June 17, 2025, the Company and the Purchasers entered into a letter agreement (the “Letter Agreement”) with each of the Purchasers in an effort 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.
Added
Stockholders’ Equity in Part II of this Annual Report on Form 10-K for more information on the Letter Agreement. Item 6. [Reserved] 55 Table of Contents

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

85 edited+77 added−48 removed64 unchanged
Biggest changeThe accompanying consolidated financial statements have been prepared assuming that the Company will continue to operate as a going concern, which contemplates the realization of assets and settlement of liabilities in the normal course of business, and do not include any adjustments to reflect the possible future effects on the recoverability and classification of assets or the amounts and classifications of liabilities that may result from uncertainty related to our ability to continue as a going concern. 71 Cash (used in) provided by operating, investing, and financing activities for the year ended December 31, 2024 and 2023 is summarized as follows (in thousands): Years Ended December 31, 2024 2023 Net cash used in operating activities $ (10,554 ) $ (12,851 ) Net cash used in investing activities (4,111 ) (160 ) Net cash provided by financing activities 6,187 3,445 Net decrease in cash and cash equivalents $ (8,478 ) $ (9,566 ) Material Cash Obligations Under the CPRIT Contract, we receive matching funds for approximately two-thirds of the development costs for the development of REYOBIQ™ for the treatment of patients with LM, subject to various funding conditions.
Biggest changeThe accompanying consolidated financial statements have been prepared assuming that the Company will continue to operate as a going concern, which contemplates the realization of assets and settlement of liabilities in the normal course of business, and do not include any 66 Table of Contents adjustments to reflect the possible future effects on the recoverability and classification of assets or the amounts and classifications of liabilities that may result from uncertainty related to our ability to continue as a going concern.
Operating activities Net cash used in operating activities for the year ended December 31, 2024 was $10.6 million compared to $12.9 million in the same period of 2023.
Net cash used in operating activities for the year ended December 31, 2024 was $10.6 million compared to $12.9 million in the same period of 2023.
Our present and future funding and cash requirements will depend on many factors, including, among other things: • the progress, timing and completion of our ongoing and planned clinical trials and nonclinical studies; • our ability to receive, and the timing of receipt of, future regulatory approvals for our product candidates and the costs related thereto; • the development and utility of the CNSide TM Test; • the scope, progress, results and costs of our ongoing and planned operations; • the costs associated with expanding our operations and building our sales and marketing capabilities; • our ability to establish strategic collaborations; • the cost and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; • the revenue, if any, received from commercial sales of our product candidates, if approved; and • potential new product candidates that the Company identifies and attempts to develop.
Our present and future funding and cash requirements will depend on many factors, including, among other things: • the progress, timing and completion of our ongoing and planned clinical trials and nonclinical studies; • our ability to receive, and the timing of receipt of, future regulatory approvals for our product candidates and the costs related thereto; • the development and utility of the CNSide Test; • the scope, progress, results and costs of our ongoing and planned operations; • the costs associated with expanding our operations and building our sales and marketing capabilities; • our ability to establish strategic collaborations; • the cost and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; • the revenue, if any, received from commercial sales of our product candidates, if approved; and • potential new product candidates that the Company identifies and attempts to develop.
In many cases, the accounting treatment of a particular transaction is dictated by U.S. GAAP, with no need for our judgment in its application. There are also areas in which our 72 judgment in selecting an available alternative would not produce a materially different result. We have identified the following as our critical accounting policies.
In many cases, the accounting treatment of a particular transaction is dictated by U.S. GAAP, with no need for our judgment in its application. There are also areas in which our judgment in selecting an available alternative would not produce a materially different result. We have identified the following as our critical accounting policies.
Actual sales of shares of common stock to Lincoln Park under the 2022 Purchase Agreement depend on a variety of factors to be determined by us from time to time, including, among others, market conditions, the trading price of the common stock and our determinations as to the appropriate sources of funding for the Company and its operations.
Actual sales of shares of common stock to Lincoln Park under the Lincoln Park Purchase Agreement depend on a variety of factors to be determined by us from time to time, including, among others, market conditions, the trading price of the common stock and our determinations as to the appropriate sources of funding for the Company and its operations.
Pursuant to the First Amendment, subject to consummation of the March 2025 Private Placement, we agreed to repurchase from the Investors the Funding Notes and 3,002,009 warrants (the “SPEA Warrants”) issued pursuant to the SPEA for an 69 aggregate purchase price of $4.25 million.
Pursuant to the First Amendment, subject to consummation of the March 2025 Private Placement, we agreed to repurchase from the Investors the Funding Notes and 3,002,009 warrants (the “SPEA Warrants”) issued pursuant to the SPEA for an aggregate purchase price of $4.25 million.
Investing activities Net cash used in investing activities for the year ended December 31, 2024 was related to purchase of Biocept assets of $0.5 million, purchase of short-term investments of $15.6 million, redemption of short-term investments of $12.2 million, and purchases of fixed assets of $0.1 million.
Net cash used in investing activities for the year ended December 31, 2024 was primarily related to purchase of Biocept assets of $0.5 million, purchase of short-term investments of $15.6 million, redemption of short-term investments of $12.2 million, and purchases of fixed assets of $0.1 million.
Potential benefits of REYOBIQ™ compared to standard external beam radiotherapy or external beam radiation therapy (“EBRT”) include: • The REYOBIQ™ radiation dose delivered to 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™ can be visualized in real-time during administration, possibly giving clinicians better control of radiation dosing, distribution and retention. • REYOBIQ™ potentially more effectively treats a bulk tumor and microscopic disease that has already invaded healthy tissue. • 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.
Potential benefits of rhenium ( 186 Re) obisbemeda compared to standard external beam radiotherapy or external beam radiation therapy (“EBRT”) include: • The rhenium ( 186 Re) obisbemeda radiation dose delivered to 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. • Rhenium ( 186 Re) obisbemeda can be visualized in real-time during administration, possibly giving clinicians better control of radiation dosing, distribution and retention. • Rhenium ( 186 Re) obisbemeda potentially more effectively treats a bulk tumor and microscopic disease that has already invaded healthy tissue. • Rhenium ( 186 Re) obisbemeda 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.
May 2024 Private Placement In May 2024, we entered into a securities purchase agreement (the “May 2024 Purchase Agreement”), which was subsequently amended, with certain investors, including certain of the Company’s directors and executive officers (the “May 2024 Private Placement Purchasers”), whereby we issued and sold in a private placement (the “May 2024 Private Placement”): (i) 3,591,532 shares of common stock or, at the election of each investor, pre-funded warrants (“Prefunded Warrants”) to purchase shares of common stock exercisable immediately at an exercise price of $0.001 per share.
May 2024 Private Placement In May 2024, we entered into a securities purchase agreement (the “May 2024 Purchase Agreement”), which was subsequently amended, with certain investors, including certain of the our directors and executive officers (the “May 2024 Private Placement Purchasers”), whereby we issued and sold in a private placement (the “May 2024 Private Placement”): (i) 3,591,532 shares of common stock or, at the election of each investor, Pre-Funded warrants (“May 2024 Pre-Funded Warrants”) to purchase shares of common stock exercisable immediately at an exercise price of $0.001 per share.
Grant Receivable represents grant funds not yet received for which the allowable expenses have been incurred as of the balance sheet date. Impairment of Goodwill We perform our goodwill impairment analysis at the reporting unit level. For the years ended December 31, 2024 and 2023, our company has one reporting unit.
Grant receivable represents grant funds not yet received for which the allowable expenses have been incurred as of the balance sheet date. Impairment of Goodwill We perform our goodwill impairment analysis at the reporting unit level. For the years ended December 31, 2025 and 2024, our company has one reporting unit.
By minimizing radiation exposure to healthy tissues while simultaneously maximizing locoregional delivery and, thereby, efficacy, we hope to reduce the radiation toxicity for patients, improving their quality of life and life expectancy. Our radiotherapeutic platform, combined with advances in surgery, nuclear medicine, interventional radiology, and radiation oncology, affords us the opportunity to target a broad variety of cancer types.
By minimizing radiation exposure to healthy tissues while simultaneously maximizing locoregional delivery and, thereby, efficacy, we hope to reduce the radiation toxicity for patients, improving their quality of life and life expectancy. Our radiotherapeutic platform, combined with advances in neurosurgery, nuclear medicine, interventional radiology, neuro-oncology, and radiation oncology, affords us the opportunity to target a broad variety of cancer types.
Pursuant to the SPEA, on the SPEA Closing Date we issued secured convertible promissory notes (the “Funding Notes”) in the aggregate principal amount of $3,362,251 together with common stock purchase warrants (the “Warrants”) to purchase 3,002,009 shares of our common stock at an exercise price of $1.12 per share.
Pursuant to the SPEA, on the SPEA Closing Date we issued secured convertible promissory notes (the 62 Table of Contents “Funding Notes”) in the aggregate principal amount of $3,362,251 together with common stock purchase warrants (the “Warrants”) to purchase 3,002,009 shares of our common stock at an exercise price of $1.12 per share.
ReSPECT-LM Clinical Trials for LM 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.
ReSPECT-LM Clinical Trials for LM 57 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.
In accordance with our accounting policy, we completed the annual evaluation for impairment of goodwill as of December 31, 2024 using the qualitative method and determined that no impairment existed.
In accordance with our accounting policy, we completed the annual evaluation for impairment of goodwill as of December 31, 2025 using the qualitative method and determined that no impairment existed.
Our lead radiotherapeutic candidate, REYOBIQ™ (rhenium ( 186 Re) obisbemeda), is designed specifically for CNS cancers including recurrent glioblastoma (“GBM”), leptomeningeal metastases (“LM”), and pediatric brain cancers (“PBC”) by direct localized delivery utilizing approved standard-of-care tissue access such as with convection-enhanced delivery (“CED”) and intraventricular brain (Ommaya reservoir) catheters.
In radiopharmaceuticals, our lead candidate, rhenium ( 186 Re) obisbemeda, is designed specifically for CNS cancers including recurrent glioblastoma (“GBM”), leptomeningeal metastases (“LM”), and pediatric brain cancers (“PBC”) by direct localized delivery utilizing approved standard-of-care tissue access such as with convection-enhanced delivery (“CED”) and intraventricular brain (Ommaya reservoir) catheters.
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™ 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.
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. • Rhenium ( 186 Re) obisbemeda 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.
Other than as described above, we have no purchase commitments or long-term contractual obligations, except for lease obligations as of December 31, 2024.
Other than as described above, we have no purchase commitments or long-term contractual obligations, except for lease obligations as of December 31, 2025.
Results of Operations Grant Revenue On September 19, 2022, we entered into the CPRIT Contract, effective as of August 31, 2022, with CPRIT, pursuant to which CPRIT will provide us a grant of up to $17.6 million (the “CPRIT Grant”) over a three-year period to fund the continued development of REYOBIQ™ for the treatment of patients with LM through Phase 2 of the ReSPECT-LM clinical trial.
Results of Operations CPRIT Grant Revenue On September 19, 2022, we entered into the CPRIT Contract, effective as of August 31, 2022, with CPRIT, pursuant to which CPRIT will provide us a grant of up to $17.6 million (the “CPRIT Grant”) over a three-year period to fund the continued development of rhenium ( 186 Re) obisbemeda for the treatment of patients with LM through Phase 2 of the ReSPECT-LM clinical trial.
Each share or Prefunded Warrant was accompanied by (i) a Series A common warrant (“May 2024 Series A Warrants”) to purchase one share of common stock, for an aggregate of 3,591,532 Series A Warrants, and (ii) one Series B common warrant (“May 2024 Series B Warrants”) to purchase one share of common stock, for an aggregate of 3,591,532 May 2024 Series B Warrants.
Each share or May 2024 Pre-Funded Warrant was accompanied by (i) a Series A common warrant (“May 2024 Series A Warrants”) to purchase one share of common stock, for an aggregate of 3,591,532 Series A Warrants, and (ii) one Series B common warrant (“May 2024 Series B Warrants”) to purchase one share of common stock, for an aggregate of 3,591,532 May 2024 Series B Warrants.
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 REYOBIQ™ for the treatment of patients with LM through Phase 2 of the ReSPECT-LM clinical trial.
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 ( 186 Re) 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 REYOBIQ™ 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.
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 ( 186 Re) 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.
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 REYOBIQ™ 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.
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 ( 186 Re) 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.
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.
Rhenium ( 186 Re) 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 rhenium ( 186 Re) obisbemeda given by CED catheters to patients with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment.
REYOBIQ™ 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.
Rhenium ( 186 Re) 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.
On an on-going basis, we evaluate our estimates and judgments, including those related to impairment assessment of our grants and awards, indefinite lived intangible assets, and share-based compensation.
On an on-going basis, we evaluate our estimates and judgments, including those related to impairment assessment of our grants and awards, indefinite lived intangible assets, share-based compensation and fair value of warrants.
Besides GBM, LM and PBC, REYOBIQ™ has been reported to have potential applications for head and neck cancer, ovarian cancer, breast cancer and peritoneal metastases. The REYOBIQ™ technology was part of a licensed radiotherapeutic portfolio that we acquired from NanoTx, Corp. (“NanoTx”) on May 7, 2020.
Besides GBM, LM and PBC, rhenium ( 186 Re) obisbemeda has been reported to have potential applications for head and neck cancer, ovarian cancer, breast cancer and peritoneal metastases. The rhenium ( 186 Re) obisbemeda technology was part of a licensed radiotherapeutic portfolio that we acquired from NanoTx, Corp. (“NanoTx”) on May 7, 2020.
REYOBIQ™ is an 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. All patients have shown well tolerated prompt and durable REYOBIQ™ distribution throughout the subarachnoid space.
Rhenium ( 186 Re) obisbemeda is an 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. All patients have shown well tolerated prompt and durable rhenium ( 186 Re) obisbemeda distribution throughout the subarachnoid space.
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™ administered through intrathecal infusion to the ventricle of patients with LM after standard surgical, radiation, and/or chemotherapy treatment.
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 rhenium ( 186 Re) obisbemeda administered through intrathecal infusion to the ventricle of patients with LM after standard surgical, radiation, and/or chemotherapy treatment.
Our operational cash use decreased by $2.3 million during the year ended December 31, 2024 as compared to the same period in 2023, due primarily to increased reimbursement under the CPRIT Contract for research and development costs related to the ReSPECT-LM program.
Cash used in operating activities decreased by $2.3 million during the year ended December 31, 2024 as compared to the same period in 2023, due primarily to increased reimbursement under the CPRIT Contract for research and development costs related to the ReSPECT-LM program.
The locally delivered REYOBIQ™ is designed for and provides patient tolerability and safety. Though no REYOBIQ™ head-to-head trial with 61 chemo, immune, EBRT or systemic radiopharmaceutical products have been conducted, patient tolerability and safety considerations have been reported as expected.
The locally delivered rhenium ( 186 Re) obisbemeda is designed for and provides patient tolerability and safety. Though no rhenium ( 186 Re) 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.
Sales of common stock by us are subject to certain limitations, and can occur from time to time, at our sole discretion, over the 36-month period commencing on August 17, 2022, subject to the satisfaction of certain conditions.
Sales of common stock by us are subject to certain limitations, and can occur from time to time, at our sole discretion, over the 36-month period commencing on June 23, 2025, subject to the satisfaction of certain conditions.
In September 2020, the FDA granted both orphan drug designation and Fast Track designations to REYOBIQ™ for the treatment of patients with GBM.
In September 2020, the FDA granted both orphan drug designation and Fast Track designations to rhenium ( 186 Re) obisbemeda for the treatment of patients with GBM.
As of December 31, 2024, we had received approximately $10.4 million in milestone payments under the CPRIT Contract. Interim results showed that a single treatment with REYOBIQ™ resulted in a consistent decreased cerebrospinal fluid (“CSF”) tumor cell count/ml and was tolerated by all LM patients.
As of December 31, 2025, we had received approximately $15.9 million in milestone payments under the CPRIT Contract. Interim results showed that a single treatment with rhenium ( 186 Re) obisbemeda resulted in a consistent decreased cerebrospinal fluid (“CSF”) tumor cell count/ml and was tolerated by all LM patients.
Share-based compensation expenses Share-based compensation expenses include charges related to options and restricted stock awards issued to employees, directors and non-employees. We measure share-based compensation expenses based on the grant-date fair value of any awards granted to our employees.
Share-based compensation expenses Share-based compensation expenses include charges related to options and restricted stock awards issued to employees, directors and non-employees. We measure share-based compensation expenses based on the grant-date fair value of any awards granted to our employees. Such expense is recognized over the requisite service period.
We anticipate beginning enrollment for our Phase 1 ReSPECT-PBC clinical trial in 2025. 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.
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 have an accumulated deficit of $493.5 million as of December 31, 2024. Additionally, we used net cash of $10.6 million to fund our operating activities for the year ended December 31, 2024. These factors raise substantial doubt about our ability to continue as a going concern.
We have an accumulated deficit of $515.9 million as of December 31, 2025. Additionally, we used net cash of $20.8 million to fund our operating activities for the year ended December 31, 2025. These factors raise substantial doubt about our ability to continue as a going concern.
Under the terms and subject to the conditions of the 2022 Purchase Agreement, we have the right, but not the obligation, to sell to Lincoln Park, and Lincoln Park is obligated to purchase up to $50.0 million of shares of our common stock, provided that we cannot sell more than 57.5 million shares pursuant to the 2022 Purchase Agreement.
Under the terms and subject to the conditions of the Lincoln Park Purchase Agreement, we have the right, but not the obligation, to sell to Lincoln Park, and Lincoln Park is obligated to purchase up to $50.0 million of shares of our common stock.
Since the inception of the CPRIT Contract, we recognized $5.8 million, $4.9 million and $0.2 million of grant revenue during the years ended December 31, 2024, 2023 and 2022, respectively, of which $10.4 million has been received and $0.6 million was recorded as 65 grant revenue receivable as of December 31, 2024.
Since the inception of the CPRIT Contract, we recognized $5.2 million, $5.8 million, $4.9 million and $0.2 million of grant revenue during the years ended December 31, 2025, 2024, 2023, and 2022, respectively, all of which had been received as of December 31, 2025.
Private Equity Lines On August 2, 2022, we entered into a purchase agreement (the “2022 Purchase Agreement”) and registration rights agreement pursuant to which Lincoln Park Capital Fund (“Lincoln Park”) committed to purchase up to $50.0 million of shares of our common stock.
Lincoln Park Purchase Agreement On June 17, 2025, we entered into a purchase agreement (the “Lincoln Park Purchase Agreement”) and a registration rights agreement pursuant to which Lincoln Park Capital Fund (“Lincoln Park”) committed to purchase up to $50.0 million of shares of our common stock.
(“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.
The CNSide Cerebrospinal Fluid Assay 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 and our board of directors appointed a board of managers for CNSide Diagnostics.
The following table summarizes the general and administrative expenses for the years ended December 31, 2024 and 2023 (in thousands): Years ended December 31, 2024 2023 General and administrative $ 9,440 $ 8,041 Share-based compensation 499 503 Total general and administrative expenses $ 9,939 $ 8,544 General and administrative expenses increased by approximately $1.4 million during the year ended December 31, 2024, as compared to the same period in 2023.
The following table summarizes the general and administrative expenses for the years ended December 31, 2025 and 2024 (in thousands): Years ended December 31, 2025 2024 General and administrative $ 10,638 $ 9,440 Share-based compensation 1,494 499 Total general and administrative expenses $ 12,132 $ 9,939 General and administrative expenses increased by approximately $2.2 million during the year ended December 31, 2025, as compared to the same period in 2024.
In May 2024, the Company issued the May 2024 Series A Warrants and May 2024 Series B Warrants and classified them as liabilities because in certain circumstances they could have been exercised into either shares of common stock or Pre-Funded Warrants at the holder’s option and thus failed the indexation guidance under Accounting Standards Codification (“ASC”) Topic 815, Derivatives and Hedging (“ASC 815”).
Changes in the fair value of the liability classified warrants will continue to be recognized until the warrants are exercised, expire or qualify for equity classification. 68 Table of Contents In May 2024, the Company issued the May 2024 Series A Warrants and May 2024 Series B Warrants and classified them as liabilities because in certain circumstances they could have been exercised into either shares of common stock or Pre-Funded Warrants at the holder’s option and thus failed the indexation guidance under Accounting Standards Codification (“ASC”) Topic 815, Derivatives and Hedging (“ASC 815”).
Short-term and long-term liquidity The following is a summary of our key liquidity measures at December 31, 2024 and 2023 (in thousands): As of December 31, 2024 2023 Cash and cash equivalents $ 76 $ 8,554 Current assets $ 5,259 $ 9,834 Current liabilities 15,551 10,727 Working capital deficit $ (10,292 ) $ (893 ) We incurred net losses of $13.0 million for the year ended December 31, 2024.
Short-term and long-term liquidity The following is a summary of our key liquidity measures at December 31, 2025 and 2024 (in thousands): As of December 31, 2025 2024 Cash, cash equivalents and restricted cash $ 8,758 $ 76 Current assets $ 15,170 $ 5,259 Current liabilities 12,314 15,551 Working capital (deficit) $ 2,856 $ (10,292 ) We incurred net losses of $22.4 million for the year ended December 31, 2025.
Financing Activities Net cash provided by financing activities for the year ended December 31, 2024 was related to net proceeds of $7.3 million raised by the May 2024 Private Placement, and drawdown of $3.3 million from the Pershing Credit Facility, offset by repurchase of common stock for approximately $0.4 million and repayment of principle balance under the Oxford term loan of $4.0 million.
Net cash provided by financing activities for the year ended December 31, 2024 was related to net proceeds of $7.3 million raised by the May 2024 Private Placement, and drawdown of $3.3 million from the Pershing Credit Facility, offset by repurchase of common stock for approximately $0.4 million and repayment of principle balance under the Oxford term loan of $4.0 million. 67 Table of Contents Critical Accounting Estimates The preparation of financial statements in conformity with accounting principles generally accepted in the United States (“U.S.
It is a rare disease with increasing U.S. annual incidence (42,000) and deaths (30,000). The FDA has informed us that 188 RNL-BAM will be regulated as a medical device under the FDCA. The CNSide™ FORESEE Trial The CNSide™ Platform consists of four LDTs used for treatment selection and treatment monitoring of patients with LM.
It is a rare disease with increasing U.S. annual incidence (42,000) and deaths (30,000). The FDA has informed us that 188 RNL-BAM will be regulated as a medical device under the FDCA.
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.
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. Pediatric high-grade gliomas can be found almost anywhere within the CNS; however, they are most commonly found within the supratentorium.
The following table summarizes the components of our research and development expenses for the years ended December 31, 2024 and 2023 (in thousands): Years ended December 31, 2024 2023 Research and development $ 10,529 $ 9,624 Share-based compensation 51 66 Total research and development expenses $ 10,580 $ 9,690 Research and development expenses for the year ended December 31, 2024 increased by $0.9 million as compared to the same period in 2023, primarily due to increases of approximately $0.7 million in development expenses, $0.1 million in compensation expenses, $1.1 million in professional research and development service fees, and $0.1 million in depreciation and other expenses, offset by a reduction of $1.1 million in research and development licensing expense and $0.1 million in clinical expenses.
The following table summarizes the components of our research and development expenses for the years ended December 31, 2025 and 2024 (in thousands): Years ended December 31, 2025 2024 Research and development $ 8,333 $ 10,529 Share-based compensation 46 51 Total research and development expenses $ 8,379 $ 10,580 Research and development expenses for the year ended December 31, 2025 decreased by $2.2 million as compared to the same period in 2024, primarily due to decreases of approximately $1.4 million in clinical development expenses, $0.9 million in compensation expenses, $0.5 million in professional research and development service fees, and $0.3 million in depreciation expense, partially offset by an increase of $0.3 million in research and development licensing expense and $0.6 million in diagnostic expenses.
In addition to the stockholder approval of the March 2025 Series A Warrants and March 2025 Series B Warrants, we also covenanted to seek if necessary stockholder approval to, among other things, amend our Certificate of Incorporation, as amended, to increase the authorized share capital to an amount sufficient to cover the shares of common stock issuable upon the exercise of the March 2025 Series A Warrants and March 2025 Series B Warrants.
On May 2, 2025, our stockholders approved, among other things, the March 2025 Series A Warrants and March 2025 Series B Warrants and an amendment of our Certificate of Incorporation, as amended, to increase the authorized share capital to an amount sufficient to cover the shares of common stock issuable upon the exercise of the March 2025 Series A Warrants and March 2025 Series B Warrants.
At the closing of the May 2024 Private Placement, we received net proceeds of approximately $7.3 million. February 2025 SPEA On February 13, 2025 (the “SPEA Closing Date”), we entered into a securities purchase and exchange agreement (the “SPEA”) with certain existing accredited investors.
February 2025 SPEA On February 13, 2025 (the “SPEA Closing Date”), we entered into a securities purchase and exchange agreement (the “SPEA”) with certain existing accredited investors.
The ReSPECT-LM Phase 1 clinical trial (ClinicalTrials.gov NCT05034497) was preceded with preclinical studies in which tolerance to doses of REYOBIQ™ as high as 1,075 Gy were shown in animal models with LM without significant observed toxicity.
The ReSPECT-LM Phase 1 clinical trial (ClinicalTrials.gov NCT05034497) was preceded with preclinical studies in which tolerance to doses of rhenium ( 186 Re) 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.
Furthermore, treatment led to a marked reduction in tumor burden in both C6 and MDA-231 LM models. 62 Upon receiving acceptance of our Investigational New Drug application and Fast Track designation by the FDA for REYOBIQ™ 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.
Upon receiving acceptance of our Investigational New Drug application and Fast Track designation by the FDA for rhenium ( 186 Re) 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.
In November 2023, the FDA granted orphan drug designation to REYOBIQ™ for the treatment of patients with breast cancer with LM. On December 12, 2023, we announced our partnership with K2bio to implement novel analysis for CSF tumor and molecular biomarkers for CNS cancers.
In November 2023, the FDA granted orphan drug designation to rhenium ( 186 Re) obisbemeda for the treatment of patients with breast cancer with LM. On December 12, 2023, we announced our partnership with K2bio to implement the CNSide Test.
The CNSide™ Platform facilitates tumor cell detection/enumeration and biomarker identification using cellular assays (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 and we are planning to re-introduce it to the US market starting in the second quarter of 2025.
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 aggregate purchase price for the Funding Note and Warrants was approximately $3.7 million and included payment of $0.125 per Warrant in accordance with the listing rules of The Nasdaq Stock Market LLC (“Nasdaq”). 68 Exchange Notes The May 2024 Purchase Agreement included certain limitations and restrictions on our ability to issue securities and provided the May 2024 Private Placement Purchasers other than our directors and executive officers (the “Outside Investors”) participation rights in future equity and equity-linked offerings of securities, subject to certain limited exceptions (the “Financing Restrictions”).
Exchange Notes The May 2024 Purchase Agreement included certain limitations and restrictions on our ability to issue securities and provided the May 2024 Private Placement Purchasers other than our directors and executive officers (the “Outside Investors”) participation rights in future equity and equity-linked offerings of securities, subject to certain limited exceptions (the “Financing Restrictions”).
Such expense is recognized over the requisite service period. 66 The following table summarizes the components of our share-based compensation expenses for the years ended December 31, 2024 and 2023 (in thousands): Years ended December 31, 2024 2023 Research and development $ 51 $ 66 General and administrative 499 503 Total share-based compensation $ 550 $ 569 Our stock-based compensation expenses, which are impacted by grants of stock-based options, vesting schedule of such grants, as well as grant-date fair value of stock-based awards, remained consistent for the year ended December 31, 2024 and 2023.
The following table summarizes the components of our share-based compensation expenses for the years ended December 31, 2025 and 2024 (in thousands): Years ended December 31, 2025 2024 Research and development $ 46 $ 51 General and administrative 1,494 499 Total share-based compensation $ 1,540 $ 550 Our share-based compensation expenses, which are impacted by grants of stock-based awards, the vesting of such grants, as well as grant-date fair value of stock-based awards, increased for the year ended December 31, 2025 as compared to the same period in 2024 due to an increased number of grants made during the year ended December 31, 2025.
We issued and sold 527,166 shares of common stock to Lincoln Park in connection with the First Registration Statement. An additional commitment fee equal to 2.5% of the remainder of the $50 million will be paid if and when we sell over $25.0 million of our common stock under the 2022 Purchase Agreement.
An additional commitment fee of $0.5 million will be paid in cash or shares of common stock, or a combination of cash and shares of common stock, if and when we sell over $25.0 million of our common stock under the Lincoln Park Purchase Agreement.
Critical Accounting Estimates The preparation of financial statements in conformity with accounting principles generally accepted in the United States (“U.S. GAAP”) requires us to make estimates and assumptions that affect the reported amounts of our assets, liabilities, revenue, and expenses, and that affect our recognition and disclosure of contingent assets and liabilities.
GAAP”) requires us to make estimates and assumptions that affect the reported amounts of our assets, liabilities, revenue, and expenses, and that affect our recognition and disclosure of contingent assets and liabilities.
The expected term assumption is estimated using the simplified method set forth in the SEC's Staff Accounting Bulletin 110, which is the mid-point between the option vesting date and the expiration date.
The expected term assumption is estimated using the simplified method set forth in the SEC's Staff Accounting Bulletin 110, which is the mid-point between the option vesting date and the expiration date. We have never declared or paid dividends on our common stock and have no plans to do so in the foreseeable future.
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.
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. In March 2025, the FDA granted orphan drug designation to rhenium ( 186 Re) obisbemeda for the treatment of LM in patients with lung cancer.
The increase was due primarily to an increase in legal and professional expenses of $1.0 million, and an increase of $0.4 million in compensation expenses. We expect general and administrative expenditures to remain generally consistent during 2025 as compared with the corresponding comparable period ended December 31, 2024.
The increase was due primarily to an increase of $2.2 million in compensation expenses. We expect general and administrative expenditures to increase in 2026 as compared with the corresponding comparable period ended December 31, 2025 as we expand the CNSide commercial operations team (including sales, customer service and laboratory operations).
Our acquired radiotherapeutic candidate, Rhenium-188 NanoLiposome Biodegradable Alginate Microsphere (“ 188 RNL-BAM”), is designed to treat many solid organ cancers including primary and secondary liver cancers by intra-arterial injection. On April 26, 2024, we acquired all of the right, title and interest in a cerebrospinal fluid cancer diagnostic portfolio known as the CNSide® Platform from Biocept, Inc.
Our acquired radiotherapeutic candidate, Rhenium-188 NanoLiposome Biodegradable Alginate Microsphere (“ 188 RNL-BAM”) is designed to treat many solid organ cancers including primary and secondary liver cancers by intra-arterial injection.
Food and Drug Administration (“FDA”) conditionally accepted the proprietary name REYOBIQ™ to be used by us for rhenium ( 186 Re) 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.
Pipeline Our most advanced investigational drug, rhenium ( 186 Re) obisbemeda, is a patented radiotherapy potentially useful for patients with CNS and other cancers. Preclinical study data describing the use of rhenium ( 186 Re) obisbemeda for several cancer targets have been published in peer-reviewed journals and reported at a variety of medical society peer-reviewed meetings.
Warrant Liability Accounting for liability classified warrants requires management to exercise judgment and make estimates and assumptions regarding their fair value.
Changes in these assumptions may lead to variability with respect to the amount of stock compensation expense we recognize related to stock options. Warrant Liability Accounting for liability classified warrants requires management to exercise judgment and make estimates and assumptions regarding their fair value.
In addition, grant revenue amounts will vary quarter to quarter based on enrollment, mandated safety periods between cohorts and required interactions with FDA . Research and development expenses Research and development expenses include costs associated with the design, development, testing, and enhancement of our product candidates, payment of regulatory fees, laboratory supplies, pre-clinical studies, and clinical studies.
Research and development expenses Research and development expenses include costs associated with the design, development, testing, and enhancement of our product candidates, payment of regulatory fees, laboratory supplies, preclinical studies, and clinical studies.
The amounts recognized represents CPRIT’s share of the costs incurred for our REYOBIQ™ development for the treatment of patients with LM. As of December 31, 2024, we had $0.6 million of grant revenue receivable related to the CPRIT Grant. In February 2025, we received $2.0 million under the CPRIT Contract.
The amounts recognized represent CPRIT’s share of the costs incurred for our rhenium ( 186 Re) obisbemeda development for the treatment of patients with LM. In 2025, we received $5.5 million under the CPRIT Contract.
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.
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.
REYOBIQ™ versus External Beam Radiation Therapy for Recurrent GBM REYOBIQ™ is a novel injectable 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.
National Institutes of Health/National Cancer Institute which is expected to provide financial support for the continued clinical development of rhenium ( 186 Re) obisbemeda for recurrent GBM through the completion of a Phase 2 clinical trial, including enrollment of up to 55 patients. 56 Table of Contents Rhenium ( 186 Re) obisbemeda versus External Beam Radiation Therapy for Recurrent GBM Rhenium ( 186 Re) obisbemeda is a novel injectable 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.
Other Income (Expense) The following table summarizes interest income, interest expense, and other income and expense for the years ended December 31, 2024 and 2023 (in thousands): Years ended December 31, 2024 2023 Interest income $ 273 $ 400 Interest expense (179 ) (395 ) Financing expense (3,545 ) — Change in fair value of warrants 5,654 — Warrant issuance costs (486 ) — Total $ 1,717 $ 5 The decrease in interest expense for the year ended December 31, 2024 as compared to the same period in 2023 was primarily due to the repayment of debt principal of $1.6 million during the year ended December 31, 2023 and $4.0 million during the year ended December 31, 2024, offset by interest expenses on our line of credit facility.
Other Income (Expense) The following table summarizes interest income, interest expense, and other income and expense for the years ended December 31, 2025 and 2024 (in thousands): Years ended December 31, 2025 2024 Interest income $ 116 $ 273 Interest expense (548 ) (179 ) Financing expense (3,061 ) (3,545 ) Change in fair value of derivative instruments (2,631 ) 5,654 Warrant issuance costs (964 ) (486 ) Total $ (7,088 ) $ 1,717 Interest income decreased for the year ended December 31, 2025 compared with the same period in 2024 primarily due to reduced accreted income on our available-for-sale securities and a lower interest rate environment in 2025.
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.
Overall, pediatric HGG and ependymoma are extremely difficult-to-treat pediatric brain tumors, frequently aggressive, and in recurrent settings, carry an extremely poor prognosis.
If the Staff finds us again out of compliance with the Minimum Stockholders’ Equity Requirement before that date, we would not be permitted to provide the Staff with a plan of compliance with respect to that deficiency and the Staff would not be permitted to grant additional time for us to regain compliance with respect to that deficiency, nor would we be afforded an applicable cure or compliance period.
If, within that one-year monitoring period, the Staff determines that we no longer satisfy the Minimum Stockholders’ Equity Requirement (and we 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.
We expect aggregate research and development expenditures to increase significantly during 2025 as compared to the corresponding comparable period ended December 31, 2024, due to increased costs for the ReSPECT-LM clinical trial (for which CPRIT grant funding is expected to be available), increases in licensing payments, offset by reduced research and development spend on the cGMP development.
We expect aggregate research and development expenditures to increase in 2026 as compared to the corresponding comparable period ended December 31, 2025, due to increased costs for the ReSPECT-LM clinical trial (for which CPRIT grant funding is expected to be 60 Table of Contents available), manufacturing scale up for rhenium ( 186 Re) obisbemeda commercial and approval trial drug availability and initial patient enrollments in the ReSPECT-PBC clinical trial together with expansion of CNSide research and development teams.
In February 2025, we received $2.0 million under the CPRIT Contract. The ability to continue to access the grant remains subject to additional FDA approval of the LM clinical trial, ability to deliver expanded drug supply and continued enrollment of patients.
The ability to continue to access the grant remains subject to additional FDA approval of the LM clinical trial, ability to deliver expanded drug supply and continued enrollment of patients. In addition, grant revenue amounts will vary quarter to quarter based on enrollment, mandated safety periods between cohorts and required interactions with FDA.
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).
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).
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.
The trial is funded through Phase 2 in large part by a National Institute of Health/National Cancer Institute grant. We completed Phase 1 of our ReSPECT-GBM Trial and are targeting full enrollment into Phase 2 by the end of 2026.
On August 18, 2023, a second registration statement (the “Second Registration Statement”) was declared effective covering the resale of up to an additional 1,500,000 shares of our common stock that we reserved for issuance and sale to Lincoln Park under the 2022 Purchase Agreement from time to time.
On August 14, 2025, a registration statement (the “Second Registration Statement”) was declared effective covering the resale of up to 33,000,000 shares of our common stock.
Net cash used in investing activities for the year ended December 31, 2023 was related to purchases of fixed assets of $0.1 million.
Operating activities Net cash used in operating activities for the year ended December 31, 2025 was $20.8 million compared to $10.6 million in the same period of 2024.
Instead, the Staff would issue a “Delist Determination Letter” and we would have an opportunity to request a hearing before the Panel regarding our continued listing.
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.
First Amendment to the February 2025 SPEA In connection with the March 2025 Purchase Agreement, we entered into that certain First Amendment to the SPEA (the “First Amendment”).
As of December 31, 2025, we had a remaining liability of approximately $4.5 million included in accounts payable and accrued expenses on our consolidated balance sheet. 64 Table of Contents First Amendment to the February 2025 SPEA In connection with the March 2025 Purchase Agreement, we entered into that certain First Amendment to the SPEA (the “First Amendment”).
As consideration for Lincoln Park’s irrevocable commitment to purchase shares of our common stock upon the terms of and subject to satisfaction of the conditions set forth in the 2022 Purchase Agreement, we paid $0.1 million in cash as an Initial Commitment Fee and issued 32,846 as the initial commitment shares to Lincoln Park in consideration for its commitment to purchase shares of our common stock at our direction under the 2022 Purchase Agreement.
As consideration for Lincoln Park’s irrevocable commitment to purchase shares of our common stock upon the terms of and subject to satisfaction of the conditions set forth in the Lincoln Park Purchase Agreement, On June 23, 2025, a registration statement (the “Initial Registration Statement”) was declared effective covering the resale of up to 17,000,000 shares of our common stock.
Nasdaq Listing Compliance 70 On March 8, 2024, we received notice from the Listing Qualifications staff of Nasdaq (the “Staff”), notifying us that we no longer complied with the requirement under Nasdaq Listing Rule 5550(b)(1) to maintain a minimum of $2.5 million in stockholders’ equity (the “Minimum Stockholders’ Equity Requirement”) for continued listing on The Nasdaq Capital Market or the alternative requirements of having a market value of listed securities of $35 million or net income from continuing operations of $500,000 in the most recently completed fiscal year or two of the last three most recently completed fiscal years.
Nasdaq Listing Compliance Minimum Stockholders’ Equity Requirement In March 2024, we received notice from the Listing Qualifications staff of Nasdaq (the “Staff”), notifying us that we no longer maintained at least $2.5 million in stockholders’ equity, as required under Nasdaq Listing Rule 5550(b)(1) (the “Minimum Stockholders’ Equity Requirement”), and also did not meet any other alternative standard.

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