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What changed in PLUS THERAPEUTICS, INC.'s 10-K2023 vs 2024

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Paragraph-level year-over-year comparison of PLUS THERAPEUTICS, INC.'s 2023 and 2024 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 2024 report.

+825 added529 removedSource: 10-K (2025-03-31) vs 10-K (2024-03-05)

Top changes in PLUS THERAPEUTICS, INC.'s 2024 10-K

825 paragraphs added · 529 removed · 220 edited across 6 sections

Item 1. Business

Business — how the company describes what it does

5 edited+411 added221 removed0 unchanged
Biggest changeGrant Revenue On September 19, 2022, the Company entered into the CPRIT Contract, effective as of August 31, 2022 , with CPRIT, pursuant to which CPRIT will provide the Company with the CPRIT Grant of up to $ 17.6 million over a three-year period to fund the continued development of rhenium ( 186 Re) obisbemeda (previously known as 186 RNL) for the treatment of patients with leptomeningeal metastases (“LM”).
Biggest changeTrial closeout procedures are now taking place including final data review and monitoring, and a clinical study report and manuscript will be prepared. 9 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.
The transaction terms also included success-based milestone and royalty payments contingent on key clinical, regulatory and sales milestones, as well as the requirement to pay 15 % of any non-dilutive monetary awards or grants received from external agencies to support product development of the nanoliposome encapsulated BMEDA-chelated radioisotope, which includes grants from the Cancer Prevention & Research Institute of Texas ("CPRIT").
The transaction terms also included success-based milestone and royalty payments contingent on key clinical, regulatory and sales milestones, as well as the requirement to pay 15% of any non-dilutive monetary awards or grants received from external agencies to support product development of the nanoliposome encapsulated BMEDA-chelated radioisotope, which includes grants from CPRIT.
The CPRIT Grant is subject to customary CPRIT funding conditions, including, but not limited to, a matching fund requirement (one dollar for every two dollars awarded by CPRIT), revenue sharing obligations upon commercialization of rhenium ( 186 Re) obisbemeda based on specific dollar thresholds and tiered low single digit royalty rates 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.
UT Health Science Center at San Antonio (“UTHSA”) License Agreement On December 31, 2021, the Company entered into a Patent and Know-How License Agreement (the “UTHSA License Agreement”) with UTHSA, pursuant to which UTHSA granted the Company 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 biodegradable alginate microspheres (BAM) containing nanoliposomes loaded with imaging and/or therapeutic payloads.
Licensing On December 31, 2021, we entered into a Patent and Technology License Agreement (the “UTHSCSA License Agreement”) with UTHSCSA, pursuant to which UTHSCSA granted us an irrevocable, perpetual, exclusive, fully paid-up license, with the right to sublicense and to make, develop, commercialize and otherwise exploit certain patents, know-how and technology related to the development of BAM containing nanoliposomes loaded with imaging and/or therapeutic payloads.
(“NanoTx”) entered into a Patent and Know-How License Agreement (the “NanoTx License Agreement”), pursuant to which NanoTx granted the Company 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. 78 The transaction terms included an upfront payment of $ 0.4 million in cash and $ 0.3 million in the Company's voting stock.
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.
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Item 1. Financ ial Statements Report of Indepen dent Registered Public Accounting Firm Shareholders and Board of Directors Plus Therapeutics, Inc. Austin, Texas Opinion on the Financial Statements We have audited the accompanying balance sheets of Plus Therapeutics, Inc.
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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.
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(the “Company”) as of December 31, 2023 and 2022, the related statements of operations, stockholders’ equity (deficit), and cash flows for each of the years then ended and the related notes (collectively referred to as the “financial statements”).
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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.
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In our opinion, the financial statements present fairly, in all material respects, the financial position of the Company at December 31, 2023 and 2022, and the results of its operations and its cash flows for each of the years then ended, in conformity with accounting principles generally accepted in the United States of America.
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Our formulations are intended to achieve elevated patient-absorbed radiation doses and extend retention times such that the clearance of the isotope occurs after significant and essentially complete radiation decay, which will contribute and provide less normal tissue/organ exposure and improved safety margins.
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Going Concern Uncertainty The accompanying financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in Note 1 to the financial statements, the Company has suffered recurring losses and negative cash flows from operations that raise substantial doubt about its ability to continue as a going concern.
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Traditional approaches to radiation therapy for cancer, such as external beam radiation, have many disadvantages including continuous treatment for four to six weeks (which is onerous for patients), that the radiation damages healthy cells and tissue, and that the amount of radiation delivered is very limited and, therefore, is frequently inadequate to fully destroy the cancer.
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Management’s plans in regard to these matters are also described in Note 1. The financial statements do not include any adjustments that might result from the outcome of this uncertainty. Basis for Opinion These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s financial statements based on our audits.
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Our targeted radiotherapeutic platform and unique investigational drugs have the potential to overcome these disadvantages by directing higher, more powerful radiation doses at the tumor—and only the tumor—potentially in a single treatment.
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We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (“PCAOB”) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.
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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.
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We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud.
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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.
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The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control over financial reporting.
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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.
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Accordingly, we express no such opinion. Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements.
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(“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.
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Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.
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We are planning for the CNSide Cerebrospinal Fluid Tumor Cell Enumeration test (the “CNSide™ Test”), which is a laboratory developed test (“LDT”), to be re-introduced to the U.S. market starting in the second quarter of 2025 after we complete a number of steps related to certifications, state licensure, payor coverages, reimbursement codes and financing.
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Critical Audit Matter The critical audit matter communicated below is a matter arising from the current period audit of the financial statements that was communicated or required to be communicated to the audit committee and that: (1) relates to accounts or disclosures that are material to the financial statements and (2) involved our especially challenging, subjective, or complex judgments.
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In March 2025, we moved our headquarters to Houston, Texas, in proximity to world-class cancer institutions and researchers. Pipeline Our most advanced investigational drug, REYOBIQ™, is a patented radiotherapy potentially useful for patients with CNS and other cancers. We announced in March 2025 that U.S.
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The communication of the critical audit matter does not alter in any way our opinion on the financial statements, taken as a whole, and we are not, by communicating the critical audit matter below, providing separate opinions on the critical audit matter or on the accounts or disclosures to which it relates.
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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.
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Determination of Research and Development Cost Associated With Recording of Grant Revenue 65 As described in Note 9 to the financial statements, in September 2022, the Company entered into a contract with the Cancer Prevention and Research Institute of Texas (“CPRIT”) pursuant to which CPRIT will provide the Company a grant of up to $17.6 million (the “CPRIT Grant”) over a three-year period.
Added
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.
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The CPRIT Grant is subject to customary CPRIT funding conditions, including, but not limited to, fund the continued development of rhenium ( 186 Re) obisbemeda for the treatment of patients with leptomeningeal metastases (“LM”).” The Company recognized $4.9 million in grant revenue from the CPRIT Grant during the year ended December 31, 2023.
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The licensed radiotherapeutic has been evaluated in preclinical studies for several cancer targets and we have an active $3.0 million award from U.S.
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We identified the determination of research and development costs incurred associated with the CPRIT Grant as a critical audit matter because of the subjectivity required to appropriately determine whether such costs satisfied the funding conditions. Auditing this element involved especially challenging and subjective auditor judgment due to the nature and extent of auditor effort required to address the matter.
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National Institutes of Health/National Cancer Institute which is expected to provide financial support for the continued clinical development of REYOBIQ™ for recurrent GBM through the completion of a Phase 2 clinical trial, including enrollment of up to 55 patients. On August 29, 2022, we announced feedback from a Type C meeting with the FDA regarding Chemistry, Manufacturing and Controls practices.
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The primary procedures we performed to address this critical audit matter included: • Reviewing the CPRIT Grant agreement to understand the conditions for which research and development costs satisfy the funding conditions. • Reviewing evidence of CPRIT’s approval of costs submitted by the Company that were applied to the CPRIT Grant funding conditions. • Inspecting a sample of vendor agreements and invoice detail to determine whether certain charges satisfy the CPRIT Grant funding conditions. /s/ BDO USA, P.C.
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The FDA indicated agreement with our proposed application of cGMP guidance for radiotherapeutics, small 7 molecule drug products and liposome drug products for REYOBIQ™ in support of ongoing and future GBM clinical trials, manufacturing scale up, and commercialization. Alignment with the FDA includes support of our proposed controls and release strategy for new drug substance and new drug product.
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We have served as the Company’s auditor since 2016. Austin, Texas March 5, 2024 66 PLUS THERAPEUTICS, INC.
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Because this product is identical for recurrent GBM, LM, and PBC, we believe alignment will be consistent for REYOBIQ™ used in other clinical development programs, including LM and PBC.
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B ALANCE SHEETS (in thousands, except share and par value data) As of December 31, 2023 2022 Assets Current assets: Cash and cash equivalents $ 8,554 $ 18,120 Other current assets 1,280 3,697 Total current assets 9,834 21,817 Property and equipment, net 906 1,324 Operating lease right-use-of assets 202 248 Goodwill 372 372 Intangible assets, net 42 94 Other assets 32 12 Total assets $ 11,388 $ 23,867 Liabilities and Stockholders’ Equity (Deficit) Current liabilities: Accounts payable and accrued expenses $ 6,631 $ 10,134 Operating lease liability 120 110 Term loan obligation, current 3,976 1,608 Total current liabilities 10,727 11,852 Noncurrent operating lease liability 85 141 Term loan obligation — 3,786 Deferred grant liability 1,924 1,643 Total liabilities 12,736 17,422 Commitments and contingencies (Note 6) Stockholders’ equity (deficit): Preferred stock, $ 0.001 par value; 5,000,000 shares authorized; 1,952 shares issued and outstanding as of December 31, 2023 and 2022 — — Common stock, $ 0.001 par value; 100,000,000 shares authorized; 4,522,656 issued and 4,444,097 outstanding as of December 31, 2023, 2,240,092 shares issued and outstanding as of December 31, 2022, respectively 5 2 Treasury stock (at cost, 78,559 shares as of December 31, 2023) ( 126 ) — Additional paid-in capital 479,274 473,628 Accumulated deficit ( 480,501 ) ( 467,185 ) Total stockholders’ equity (deficit) ( 1,348 ) 6,445 Total liabilities and stockholders’ equity (deficit) $ 11,388 $ 23,867 See Accompanying Notes to these Financial Statements 67 PLUS THERAPEUTICS, INC.
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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.
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STATEMENTS OF OPE RATIONS (in thousands, except share and per share data) For the Years Ended December 31, 2023 2022 Grant revenue $ 4,913 $ 224 Operating expenses: Research and development 9,690 9,698 General and administrative 8,544 10,238 Total operating expenses 18,234 19,936 Operating loss ( 13,321 ) ( 19,712 ) Other income (expense): Interest income 400 147 Interest expense ( 395 ) ( 711 ) Change in fair value of liability instruments — 1 Total other income (expense) 5 ( 563 ) Net loss $ ( 13,316 ) $ ( 20,275 ) Net loss per share, basic and diluted $ ( 4.24 ) $ ( 11.58 ) Basic and diluted weighted average shares used in calculating net loss per share attributable to common stockholders 3,140,925 1,750,350 See Accompanying Notes to these Financial Statements 68 PLUS THERAPEUTICS, INC.
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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.
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STATEMENTS OF ST OCKHOLDERS’ EQUITY (DEFICIT) (in thousands, except share data) Convertible Additional Total Preferred Stock preferred stock Common stock paid-in Accumulated stockholders’ Shares Amount Shares Amount Shares Amount Treasury Stock capital deficit equity (deficit) Balance at December 31, 2021 — — 1,952 — 1,034,002 1 — — 457,745 ( 446,910 ) 10,836 Share-based compensation — — — — — — — — 606 — 606 Sale of common stock, net — — — — 1,206,090 1 — — 15,277 — 15,278 Net loss — — — — — — — — — ( 20,275 ) ( 20,275 ) Balance at December 31, 2022 — $ — 1,952 $ — 2,240,092 $ 2 — $ — $ 473,628 $ ( 467,185 ) $ 6,445 Issuance of Series F preferred stock 1 — — — — — — — — — — Redemption of Series F preferred stock ( 1 ) — — — — — — — — — — Share-based compensation — — — — — — — — 569 — 569 Sale of common stock, net — — — — 2,230,493 3 — — 5,002 — 5,005 Issuance of common stock for in process research and development — — — — 53,381 — — — 75 — 75 Fractional adjustment — — — — ( 1,310 ) — — — — — — Purchase of treasury stock — — — — — — ( 78,559 ) ( 126 ) — — ( 126 ) Net loss — — — — — — — — — ( 13,316 ) ( 13,316 ) Balance at December 31, 2023 — $ — 1,952 $ — 4,522,656 $ 5 ( 78,559 ) $ ( 126 ) $ 479,274 $ ( 480,501 ) $ ( 1,348 ) See Accompanying Notes to these Financial Statements 69 PLUS THERAPEUTICS, INC.
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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.
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STATEM ENTS OF CASH FLOWS (in thousands) For the Years Ended December 31, 2023 2022 Cash flows used in operating activities: Net loss $ ( 13,316 ) $ ( 20,275 ) Adjustments to reconcile net loss to net cash used in operating activities: Depreciation and amortization 628 619 Amortization of deferred financing costs and debt discount 190 389 Common stock issued for research and development 75 — Change in fair value of liability instruments — ( 1 ) Loss on disposal of property and equipment 2 — Share-based compensation expense 569 606 Reduction in the carrying amount of operating lease right-of-use assets 117 93 Increases (decreases) in cash caused by changes in operating assets and liabilities: Other assets 2,397 ( 2,369 ) Accounts payable and accrued expenses ( 3,677 ) 6,452 Change in operating lease liabilities ( 117 ) ( 129 ) Deferred grant liability 281 1,643 Net cash used in operating activities ( 12,851 ) ( 12,972 ) Cash flows used in investing activities: Purchases of property and equipment and intangible assets ( 160 ) ( 509 ) In process research and development acquired — ( 250 ) Net cash used in investing activities ( 160 ) ( 759 ) Cash flows from financing activities: Principal payments of long-term obligations ( 1,608 ) ( 1,608 ) Gross proceeds from sale of common stock 5,527 15,832 Payment of offering costs related to sale of common stock ( 348 ) ( 773 ) Purchase of treasury stock ( 126 ) — Net cash provided by financing activities 3,445 13,451 Net decrease in cash and cash equivalents ( 9,566 ) ( 280 ) Cash and cash equivalents at beginning of period 18,120 18,400 Cash and cash equivalents at end of period $ 8,554 $ 18,120 Supplemental disclosure of cash flows information: Cash paid during period for: Interest $ 222 $ 327 Supplemental schedule of non-cash investing and financing activities: Unpaid offering cost $ 174 $ — Common stock issued in payment for in process research and development $ 75 $ — Right-of-use assets acquired by assuming operating lease liabilities $ 71 $ — See Accompanying Notes to these Financial Statements 70 PLUS THERAPEUTICS, INC.
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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.
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NOTES TO FINANCIAL STATEMENTS December 31, 2023 1. Organization and Operations The Company Plus Therapeutics, Inc. is a clinical-stage pharmaceutical company focused on the development, manufacture and commercialization of complex and innovative treatments for patients battling cancer and other life-threatening diseases.
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ReSPECT-GBM Trial for Recurrent GBM GBM affects approximately 15,000 patients annually in the U.S. and is the most common and lethal form of brain cancer. The average life expectancy with GBM is less than 24 months, with a one-year survival rate of 40% and a five-year survival rate of around 5%.
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Certain Risks and Uncertainties The Company’s prospects are subject to the risks and uncertainties frequently encountered by companies in the early stages of development and commercialization, especially those companies in rapidly evolving and technologically advanced industries such as the biotech/medical device field.
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There is no clear standard of care for recurrent GBM and the few currently approved treatments provide only marginal survival benefit and are associated with significant side effects, which limit dosing and prolonged use.
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The Company’s future viability largely depends on its ability to complete development of new products and receive regulatory approvals for those products. No assurance can be given that the Company’s new products will be successfully developed, regulatory approvals will be granted, or acceptance of these products will be achieved.
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Approximately 90% of patients experience GBM tumor recurrence at or near the original tumor location, yet there are no FDA-approved treatments in the recurrent or progressive setting that can significantly extend a patient’s life. GBM routinely presents with headaches, seizures, vision changes and other significant neurological complications, with a significant compromise in quality of life.
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Going Concern The Company incurred net losses of $ 13.3 million for the year ended December 31, 2023, and as of December 31, 2023, the Company had an accumulated deficit of $ 480.5 million and cash and cash equivalents of $ 8.6 million.
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Despite the best available medical treatments, the disease remains incurable. Even after efforts to manage the presenting signs and symptoms and completely resect the initial brain tumor, some microscopic disease almost always remains and tumor regrowth occurs within months.
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Additionally, the Company used net cash of $ 12.9 million to fund its operating activities for the year ended December 31, 2023. The Company's term loan has an outstanding principal of $ 0.8 million principal and a $ 3.2 million final payment fee due June 1, 2024 (Note 8).
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Complete surgical removal of GBM is usually not possible and GBM is often resistant or quickly develops resistance to most available current and investigational therapies.
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The Company expects that its research and development expenditures will increase in absolute dollars in 2024 and beyond. These factors raise substantial doubt about the Company’s ability to continue as a going concern. As disclosed in more detail in Note 12, the Company has entered into various financing agreements and raised capital by issuing its common stock.
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Today, the treatment of GBM remains a significant challenge and it has been nearly a decade since the FDA approved a new therapy for this disease, and these more recent approvals have not improved the overall survival (“OS”) for GBM patients over past decades, and a significant unmet medical need persists.
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Based on the Company’s stockholders’ deficit of $ 1.3 million as of December 31, 2023, the Company does not meet the minimum stockholders’ equity requirement for continued listing on the Nasdaq Capital Market under Nasdaq Listing Rule 5550(b)(1).
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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.
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The Company expects to receive written notice from Nasdaq staff to that effect following the filing of the Annual Report on Form 10-K in which these financial statements are included. The Company continues to seek additional capital through strategic transactions and from other financing alternatives.
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Because of this limitation, EBRT cannot provide a cure or long-term control of GBM and GBM always recurs within months after EBRT.
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Without additional capital, current working capital and cash generated from sales will not provide adequate funding to make debt repayments, for research, sales and marketing efforts and product development activities at their current levels.
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In contrast, locally delivered and targeted radiopharmaceuticals that precisely deliver radiation in the form of beta particles such as Iodine-131 for thyroid cancer, are known to be safe and effective and minimize exposure to normal cells and tissues especially with optimal administered dose and minimizing exposure to normal tissue.
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If sufficient capital is not raised, the Company will at a minimum need to significantly reduce or curtail its research and development and other operations, and this would negatively affect its ability to achieve corporate growth goals. Should the Company fail to raise additional cash from outside sources, this would have a material adverse impact on its operations.
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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.
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The accompanying financial statements have been prepared assuming 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 its ability to continue as a going concern.
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In September 2020, the FDA granted both orphan drug designation and Fast Track designations to REYOBIQ™ for the treatment of patients with GBM.
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Amendments to Certificate of Incorporation and Reverse Stock Split At the Annual Meeting of Stockholders of the Company held on April 20, 2023 (the “Annual Meeting”), the stockholders of the Company approved an amendment to the Company’s Amended and Restated Certificate of Incorporation (the “Charter”) to implement a reverse stock split of the Company’s common stock, par value $ 0.001 per share, with the ratio to be determined by the Board of Directors (the “Board”) of the Company, within a range of not less than 1-for-3 and not greater than 1-for-15 .
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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.
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Subsequently, on April 21, 2023, the Board determined to fix the ratio for the reverse stock split at 1-for-15 , without any change to its par value (the "Reverse Stock Split").
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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.
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On April 27, 2023, following stockholder and Board approval, the Company filed a Certificate of Amendment to its Charter (the “Amendment”), with the Secretary of State of the State of Delaware to effectuate the Reverse Stock Split. The Amendment became effective on May 1, 2023 .
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Phase 2 of the trial is expected to enroll up to 34 total patients with small- to medium-sized tumors and is targeted for full enrollment by the end of 2025. We currently have four clinical sites, and expect a data read-out by the end of 2025.
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Upon effectiveness of the Reverse Stock Split, the number of shares of the Company’s common stock 71 (x) issued and outstanding decreased from approximately 37.4 million shares to approximately 2.5 million shares; (y) reserved for issuance upon exercise of outstanding warrants and options decreased from approximately 2.0 million shares to app roximately 0.1 million shares, and (z) reserved but unallocated under the Company’s current equity incentive plans decreased from approximately 3.0 million common shares to approximately 0.2 million common shares.
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On September 30, 2024, we showcased new interim ReSPECT-GBM Phase 2 Trial Data at the 2024 Congress of Neurological Surgeons Annual Meeting that included the following findings as of that date: • 42 total patients enrolled in ReSPECT-GBM trial at 3 sites, with 19 out of 42 patients having been treated at the recommended Phase 2 dose (22.3 mCi in 8.8 mL) in tumors of approximately 20 cm 3 or less. • All Phase 2 patients have recurrent, histologically confirmed glioblastoma; 1 recurrence, bevacizumab naïve, single tumor of approximately 20 cm 3 or less (small-to-medium sized tumors). • Average tumor size in Phase 2 was 7.5 mL (range 0.9-22.8 mL). • Increases in absorbed dose correlated with specific drug delivery parameters such as infused dose and volume, maximal convection flow rate, and number of catheters. • REYOBIQ™ continues to show a favorable safety profile in the 42 enrolled patients; one dose-limiting toxicity (hemiplegia) has been reported, which was observed in Cohort 8 (41.5 mCi and 16.3 mL). • In Phase 2, most adverse events were mild (73.5%) or moderate (18.8%), and largely unrelated (37.7%), or unlikely related (27.1%) to the drug.
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The Company's common stock began trading on the NASDAQ Capital Market on a post-split basis on May 1, 2023. The Company’s 5,000,000 shares of authorized Preferred Stock were not affected by the Reverse Stock Split.
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Of the 9 severe adverse events, only 2 were related to the study drug. • Average absorbed radiation dose to the tumor in Phase 2 was 300 Gy (n=18, 1 patient still under analysis). • 88.9% of Phase 2 patients met key CED drug delivery parameters shown to correlate with overall survival, achieving a tumor absorbed dose >100 Gy and radiation coverage of >70%. • 29 out of 42 patients treated thus far participated in the Phase 1 dose escalation phase of the trial (as per protocol, 6 out of 42 patients were included in both the Phase 1 and Phase 2 trial arms and related analyses). • Phase 1 dose-escalation increased administered doses from 1.0 mCi to 41.5 mCi and volumes from 0.66 mL to 16.3 mL. • In terms of objective tumor response based on quantitative image analysis, a statistically significant reduction in tumor volume rate change was seen in tumors receiving > 100 Gy absorbed dose (n=11 patients analyzed to date, p We completed Phase 1 of our ReSPECT-GBM Trial and are targeting full enrollment into Phase 2 by the end of 2025.
Removed
No fractional shares were issued in connection with the Reverse Stock Split, and accordingly, the outstanding number of shares post Reverse Stock Split was adjusted down by approximately 1,310 (post-effect of Reverse Stock Split) shares.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeIf, for any reason, Nasdaq were to delist our securities from trading on its exchange and we are unable to obtain listing on another reputable national securities exchange, a reduction in some or all of the following may occur, each of which could materially adversely affect our stockholders: the liquidity and marketability of our common stock; the market price of our common stock; our ability to obtain financing for the continuation of our operations; the number of institutional and general investors that will consider investing in our common stock; the number of market makers in our common stock; the availability of information concerning the trading prices and volume of our common stock; and the number of broker-dealers willing to execute trades in shares of our common stock. 27 In addition, if we cease to be eligible to trade on Nasdaq, we may have to pursue trading on a less recognized or accepted market, such as the over the counter markets, our stock may be traded as a “penny stock,” which would make transactions in our stock more difficult and cumbersome, and we may be unable to access capital on favorable terms or at all, as companies trading on alternative markets may be viewed as less attractive investments with higher associated risks, such that existing or prospective institutional investors may be less interested in, or prohibited from, investing in our common stock.
Biggest changeIn the event that our common stock is delisted from Nasdaq, as a result of our failure to comply with the Minimum Stockholders’ Equity Requirement, or as a result of our failure to continue to comply with any other requirement for continued listing on Nasdaq, we may have to pursue trading on a less recognized or accepted market, such as the over the counter markets, our stock may be traded as a “penny stock,” which would make transactions in our common stock more difficult and cumbersome, and we may be unable to access capital on favorable terms or at all, as companies trading on alternative markets may be viewed as less attractive investments with higher associated risks, such that existing or prospective institutional investors may be less interested in, or prohibited from, investing in our common stock.
These requirements include, among other things, maintaining a closing bid price for our common stock of $1.00 per share (the “minimum bid price requirement”) and meeting one of the following three requirements: maintaining at least $2.5 million in stockholders’ equity; maintaining $35 million of market value of listed securities; or having $500,000 in net income over the prior two years or two of the prior three years.
These requirements include, among other things, maintaining a closing bid price for our common stock of $1.00 per share and meeting one of the following three requirements: maintaining at least $2.5 million in stockholders’ equity (the “Minimum Stockholders’ Equity Requirement”); maintaining $35 million of market value of listed securities; or having $500,000 in net income over the prior two years or two of the prior three years.
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, 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.
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; 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; 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.
These disruptions and challenges could result from actual or perceived quality, oversight, or regulatory compliance problems; natural disasters (including increased instances or severity of natural disasters or other events that may be due to climate change), public health outbreaks, epidemics, or pandemics; periods of uneven economic growth or downturns; emergence or escalation of, and responses to international tension and conflicts; equipment, mechanical, data, or information technology system (“IT system”) vulnerabilities, such as system inadequacies, inadequate controls or procedures, operating failures, unauthorized access, service interruptions or failures, security breaches, malicious intrusions, theft, exfiltration, ransomware or other cyber-attacks from a variety of sources; labor shortages; challenges and complexities in manufacturing new drug 41 modalities; contractual disputes with our suppliers and contract manufacturers; vertical integration by competitors within our supply chain; or inability to obtain single-source or other raw or intermediate materials.
These disruptions and challenges could result from actual or perceived quality, oversight, or regulatory compliance problems; natural disasters (including increased instances or severity of natural disasters or other events that may be due to climate change), public health outbreaks, epidemics, or pandemics; periods of uneven economic growth or downturns; emergence or escalation of, and responses to international tension and conflicts; equipment, mechanical, data, or information technology system (“IT system”) vulnerabilities, such as system inadequacies, inadequate controls or procedures, operating failures, unauthorized access, service interruptions or failures, security breaches, malicious intrusions, theft, exfiltration, ransomware or other cyber-attacks from a variety of sources; labor shortages; challenges and complexities in manufacturing new drug modalities; contractual disputes with our suppliers and contract manufacturers; vertical integration by competitors within our supply chain; or inability to obtain single-source or other raw or intermediate materials.
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 32 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; 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.
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.
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.
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 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 or clearances of future or pending product submissions, fines, recalls, import or seizures of products, total or partial suspensions of production and criminal prosecution.
In addition, regardless of merit or eventual outcome, product liability claims may result in: the inability to commercialize our product candidates; decreased demand for our product candidates, if approved; impairment of our business reputation; product recall or withdrawal from the market; withdrawal of clinical trial participants; costs of related litigation; 43 distraction of management’s attention from our primary business; substantial monetary awards to patients or other claimants; or loss of revenue.
In addition, regardless of merit or eventual outcome, product liability claims may result in: the inability to commercialize our product candidates; decreased demand for our product candidates, if approved; impairment of our business reputation; product recall or withdrawal from the market; withdrawal of clinical trial participants; costs of related litigation; distraction of management’s attention from our primary business; substantial monetary awards to patients or other claimants; or loss of revenue.
Depending on their nature and scope, such threats could potentially lead to the compromising of confidential information and communications, improper use of our systems and networks, manipulation and destruction of data, defective products, production downtimes and operational disruptions, which in turn could adversely affect our reputation, competitiveness and results of operations. 49 Item 1B. Unresolv ed Staff Comments None.
Depending on their nature and scope, such threats could potentially lead to the compromising of confidential information and communications, improper use of our systems and networks, manipulation and destruction of data, defective products, production downtimes and operational disruptions, which in turn could adversely affect our reputation, competitiveness and results of operations. Item 1B. Unresolv ed Staff Comments None.
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.
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.
If our competitors market or develop products that are marketed more effectively, approved more quickly than our product candidates, or demonstrated to be safer or more effective than our product candidates, our commercial opportunities could be reduced or eliminated. 33 The life science industry is characterized by rapidly advancing technologies, intense competition, and a strong emphasis on proprietary therapeutics.
If our competitors market or develop products that are marketed more effectively, approved more quickly than our product candidates, or demonstrated to be safer or more effective than our product candidates, our commercial opportunities could be reduced or eliminated. The life science industry is characterized by rapidly advancing technologies, intense competition, and a strong emphasis on proprietary therapeutics.
We cannot be sure whether additional legislative changes will be enacted, or whether FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals, if any, of our drug 39 candidates, may be or whether such changes will have any other impacts on our business. In addition, increased scrutiny by the U.S.
We cannot be sure whether additional legislative changes will be enacted, or whether FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals, if any, of our drug candidates, may be or whether such changes will have any other impacts on our business. In addition, increased scrutiny by the U.S.
The U.S. government also has the right to take title to these inventions if we, or the applicable licensor, fail to disclose the invention to the government and fail to file an application to register the intellectual property within specified 40 time limits. These time limits have recently been changed by regulation and may change in the future.
The U.S. government also has the right to take title to these inventions if we, or the applicable licensor, fail to disclose the invention to the government and fail to file an application to register the intellectual property within specified time limits. These time limits have recently been changed by regulation and may change in the future.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
We expect that product candidates in our pipeline, if approved, to compete on the basis of, among other things, product efficacy and safety, time to market, price, coverage, and reimbursement by third-party payers, extent of adverse side effects, and convenience of treatment procedures.
We expect the product candidates in our pipeline, if approved, to compete on the basis of, among other things, product efficacy and safety, time to market, price, coverage, and reimbursement by third-party payers, extent of adverse side effects, and convenience of treatment procedures.
Furthermore, we may be unable to identify suitable product candidates or technologies within our area of focus. If we are unable to successfully obtain rights to suitable product candidates or technologies undertake or to successfully complete any additional transactions of the nature described above, our business, financial condition and prospects could suffer.
Furthermore, we may be unable to identify suitable product candidates or technologies within our area of focus. If we are unable to successfully obtain rights to suitable product candidates or technologies or to successfully complete any additional transactions of the nature described above, our business, financial condition and prospects could suffer.
A failure to adequately protect private health information could result in severe harm to our reputation and subject us to significant liabilities, each of which could have a material adverse effect on our business. Throughout the clinical trial process, we may obtain the private health information of our trial subjects.
A failure to adequately protect health information could result in severe harm to our reputation and subject us to significant liabilities, each of which could have a material adverse effect on our business. Throughout the clinical trial process, we may obtain the health information of our trial subjects.
Depending on the type and the terms of any financing we pursue, stockholders’ rights and the value of their investment in our common stock could be reduced. A financing could involve one or more types of securities including common stock, convertible debt or warrants to acquire common stock.
Depending on the type and the terms of any financing we pursue, stockholders’ rights and the value of their investment in our common stock could be reduced. A financing could involve one or more types of securities including common stock, preferred stock, convertible debt or warrants to acquire common stock.
The amount and timing of our future funding requirements will depend on many factors, including the pace and results of its clinical development efforts. We have secured capital historically from grant revenue, collaboration proceeds, and debt and equity offerings.
The amount and timing of our future funding requirements will depend on many factors, including the pace and results of our clinical development efforts. We have secured capital historically from grant revenue, collaboration proceeds, and debt and equity offerings.
A number of companies in the pharmaceutical and biotechnology industries, including us and many other companies with greater resources and experience than we, 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 pre-clinical studies and clinical trials.
If we 35 fail to produce positive results in our planned clinical trials of any of our product candidates, the development timeline and regulatory approval and commercialization prospects for our product candidates, and, correspondingly, our business and financial prospects, could be materially adversely affected.
If we fail to produce positive results in our planned clinical trials of any of our product candidates, the development timeline and regulatory approval and commercialization prospects for our product candidates, and, correspondingly, our business and financial prospects, could be materially adversely affected.
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 (“CRO”), 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; 34 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 contract research organization (“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 ask us to 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; 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).
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.
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.
The research, testing, manufacturing, labeling, approval, sale, 31 marketing and distribution of products are subject to extensive regulation by the FDA and other regulatory authorities in the United States and other countries, whose regulations differ from country to country.
The research, testing, manufacturing, labeling, approval, sale, marketing and distribution of products are subject to extensive regulation by the FDA and other regulatory authorities in the United States and other countries, whose regulations differ from country to country.
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 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 pre-clinical studies and early clinical trials of our product candidates may not be replicated in subsequent clinical trials.
Our future capital requirements will depend on many factors, including: our ability to raise capital to fund our operations on terms acceptable to us, or at all; our perceived capital needs with respect to our development programs, and any delays in, adverse events and excessive costs of such programs beyond what we currently anticipate; our ability to establish and maintain collaborative and other arrangements with third parties to assist in bringing our product candidates to market and the cost of such arrangements at the time; costs associated with operating at our San Antonio, Texas facility; the cost of manufacturing our product candidates, including compliance with good manufacturing practices applicable to our product candidates; expenses related to the establishment of sales and marketing capabilities for product candidates awaiting approval or products that have been approved; competing technological and market developments; and our ability to introduce and sell new products.
Our future capital requirements will depend on many factors, including: our ability to raise capital to fund our operations on terms acceptable to us, or at all; our perceived capital needs with respect to our development programs, and any delays in, adverse events and excessive costs of such programs beyond what we currently anticipate; our ability to establish and maintain collaborative and other arrangements with third parties to assist in bringing our product candidates to market and the cost of such arrangements at the time; costs associated with operating at our Houston, Texas facility; the cost of manufacturing our product candidates, including compliance with good manufacturing practices applicable to our product candidates; expenses related to the establishment of sales and marketing capabilities for product candidates awaiting approval or products that have been approved; competing technological and market developments; and our ability to introduce and sell new products.
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. 46 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. 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.
The manufacture of our product candidates is, and the manufacture of any future drug and/or cell-related therapeutic products would be, subject to periodic inspection by regulatory authorities and distribution partners.
The manufacture of our product candidates is, and the manufacture of any future drug, device, and/or cell-related therapeutic products would be, subject to periodic inspection by regulatory authorities and distribution partners.
Competitors may have greater experience in developing drugs, 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, or clearance from the FDA or achieve commercialization earlier than we can, any of which could have a substantial negative effect on our business.
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. 45 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. 52 We may not be able to protect our trade secrets.
Some of the intellectual property rights we have licensed are generated through the use of U.S. government funding and are therefore subject to certain federal regulations. As a result, the U.S. government may have certain rights to intellectual property embodied in our current or future product candidates pursuant to the Bayh-Dole Act of 1980, or Bayh-Dole Act, and implementing regulations.
Some of the intellectual property rights we have licensed are generated through the use of U.S. government funding and are therefore subject to certain federal regulations. As a result, the U.S. government may have certain rights to intellectual property embodied in our current or future product candidates pursuant to the Bayh-Dole Act of 1980 (the “Bayh-Dole Act”), and implementing regulations.
In addition, the U.S. government has the right to require us or our licensors to grant exclusive, partially exclusive, or non-exclusive licenses to any of these inventions to a third party if it determines that: (i) adequate steps have not been taken to commercialize the invention; (ii) government action is necessary to meet public health or safety needs; or (iii) government action is necessary to meet requirements for public use under federal regulations (also referred to as "march-in rights").
In addition, the U.S. government has the right to require us or our licensors to grant exclusive, partially exclusive, or non-exclusive licenses to any of these inventions to a third party if it determines that: (i) adequate steps have not been taken to commercialize the invention; (ii) government action is necessary to meet public health or safety needs; or (iii) government action is necessary to meet requirements for public use under federal regulations (also referred to as “march-in” rights).
We are dependent on sole source suppliers to manufacture the active pharmaceutical ingredients ("API") and certain other components of our nanomedicine product candidates. There is no assurance that these sole source suppliers will enter into supply agreements with us to provide contractual assurance to us around supply and pricing.
We are dependent on sole source suppliers to manufacture the active pharmaceutical ingredients (“API”) and certain other components of our nanomedicine product candidates. There is no assurance that these sole source suppliers will enter into supply agreements with us to provide contractual assurance to us around supply and pricing.
Failure to comply with the CCPA may result in, among other things, significant civil penalties and injunctive relief, or statutory or actual damages. In addition, California residents have the right to bring a private right of action in connection with certain types of incidents. These claims may result in significant liability and damages.
Failure to comply with the CCPA may result in, among other things, significant civil penalties and injunctive relief, or statutory or actual damages. In addition, California consumers have the right to bring a private right of action in connection with certain types of incidents. These claims may result in significant liability and damages.
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, 2024 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, 2025 as we perform clinical trials and other development activities for our nanomedicine product candidates.
We must perform system and process evaluation and testing of our internal control over financial reporting to allow management to report on the effectiveness of our internal controls over financial reporting in our Form 10-K and Form 10-Q, as required by Section 404 of the Sarbanes-Oxley Act.
We must perform system and process evaluation and testing of our internal control over financial reporting to allow management to report on the effectiveness of our internal controls over financial reporting in each Form 10-K, as required by Section 404 of the Sarbanes-Oxley Act.
Further, even after an orphan drug is approved, the FDA can subsequently approve a drug with similar chemical structure for the same condition if the FDA concludes that the new drug is clinically superior to the orphan product or a market shortage occurs.
Further, even after an orphan drug is approved, the FDA can subsequently approve a drug with similar chemical structure for the same indication if the FDA concludes that the new drug is clinically superior to the orphan product or a market shortage occurs.
Anticipated or unanticipated changes in the way or manner in which the FDA or other regulators regulate products or classes and groups of products can delay, further burden, or alleviate regulatory pathways that were once available to other products.
Anticipated or unanticipated changes in the way or manner in which the FDA or other regulators regulate products or classes and groups of products, including LDTs, can delay, further burden, or alleviate regulatory pathways that were once available to other products.
Some intellectual property that we have in-licensed has been discovered through government funded programs and thus may be subject to federal regulations such as "march-in" rights, certain reporting requirements and a preference for U.S.-based companies. Compliance with such regulations may limit our exclusive rights and limit our ability to contract with non-U.S. manufacturers.
Some intellectual property that we have in-licensed has been discovered through government funded programs and thus may be subject to federal regulations such as “march-in” rights, certain reporting requirements and a preference for U.S.-based companies. Compliance with such regulations may limit our exclusive rights and limit our ability to contract with non-U.S. manufacturers.
If we are unsuccessful in our efforts to develop these assets, or if UTHSA and we were to enter into a dispute over the terms of our agreement, then our business could be seriously harmed.
If we are unsuccessful in our efforts to develop these assets, or if UTHSCSA and we were to enter into a dispute over the terms of our agreement, then our business could be seriously harmed.
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 Federal Food, Drug and Cosmetic Act, and/or in international markets such as Europe, 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; 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.
In the European Union, orphan exclusivity may be reduced to six years if the drug no longer satisfies the original designation criteria or can be lost altogether if the marketing authorization holder consents to a second orphan drug application or cannot supply enough drug, or when a second applicant demonstrates its drug is “clinically superior” to the original orphan drug.
In the EU, orphan exclusivity may be reduced to six years if the drug no longer satisfies the original designation criteria or can be lost altogether if the marketing authorization holder consents to a second orphan drug application or cannot supply enough drug, or when a second applicant demonstrates its drug is “clinically superior” to the original orphan drug.
Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing conditions and other requirements. In the European Union, similar political, economic and regulatory developments may affect our ability to profitably commercialize our product candidates.
Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing conditions and other requirements. In the EU, similar political, economic and regulatory developments may affect our ability to profitably commercialize our product candidates.
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 EMA), and we may never receive such regulatory approvals.
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.
In the European Union, the EMA’s Committee for Orphan Medicinal Products, grants orphan drug designation to promote the development of products that are intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than 10,000 persons in the European Union.
In the EU, the EMA’s Committee for Orphan Medicinal Products grants orphan drug designation to promote the development of products that are intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than 10,000 persons in the EU.
We, our collaborators, and our and their respective contractors, suppliers and vendors, will be subject to ongoing regulatory requirements, including complying with regulations and laws regarding advertising, promotion and sales of products (including applicable anti-kickback, fraud and abuse and other health care laws and regulations), required submissions of safety and other post-market information and reports, registration requirements, Clinical Good Manufacturing Practices regulations (including requirements relating to quality control and quality assurance, as well as the corresponding maintenance of records and documentation), and the requirements regarding the distribution of samples to physicians and recordkeeping requirements.
We, our collaborators, and our and their respective contractors, suppliers and vendors, will be subject to ongoing regulatory requirements, including complying with regulations and laws regarding advertising, promotion and sales of products (including applicable anti-kickback, fraud and abuse and other health care laws and regulations), required submissions of safety and other post-market information and reports, registration requirements, cGMP regulations (including requirements relating to quality control and quality assurance, as well as the corresponding maintenance of records and documentation), and the requirements regarding the distribution of samples to physicians and recordkeeping requirements.
For example: we, NanoTx, or UTHSA, as the case may be, might not have been the first to file patent applications for the covered inventions; 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 188RNL-BAM product candidates but that are not covered by the claims of our patents; we may not be able to detect infringement against our patents, which may be especially difficult for manufacturing processes or formulation patents, such as the patents/applications related to 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.
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.
One or more of our competitors may develop other products that compete with ours, obtain necessary approvals for such products from the FDA, EMA, 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.
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.
We could potentially be subject to criminal penalties if we, our affiliates, or our agents knowingly use or disclose individually identifiable health information maintained by a HIPAA-covered entity in a manner that is not authorized or permitted by HIPAA.
We could potentially be subject to criminal penalties if we, our affiliates, or our agents knowingly receive individually identifiable health information maintained by a HIPAA-covered entity in a manner that is not authorized or permitted by HIPAA.
Our current business strategy is to aggressively develop our nanomedicine platforms, 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; 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 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 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 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 expertise necessary to develop, manufacture, and commercialize our nanomedicine product candidates.
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.
If we are unable to attract personnel with the necessary skills and experience to reestablish and expand our nanomedicine business, which is currently conducted out of our San Antonio, Texas facility, our business could suffer.
If we are unable to attract personnel with the necessary skills and experience to reestablish and expand our nanomedicine business, which is currently conducted out of our Houston, Texas facility, our business could suffer.
Because some of our products compete in a market with both branded and generic products, obtaining and maintaining access and reimbursement coverage for our products may be more challenging than for products that are new chemical entities for which no therapeutic alternatives exist.
Because some of our product candidates, once commercialized, may compete in a market with both branded and generic products, obtaining and maintaining access and reimbursement coverage for our products may be more challenging than for products that are new chemical entities for which no therapeutic alternatives exist.
In both U.S. and non-U.S. markets, our ability to successfully commercialize and achieve market acceptance of our products depends in significant part on adequate financial coverage and reimbursement from third party payors, including governmental payors (such as the Medicare and Medicaid programs in the U.S.), managed care organizations and private health insurers.
In both U.S. and non-U.S. markets, our ability to successfully commercialize and achieve market acceptance of our product candidates, if approved, depends in significant part on adequate financial coverage and reimbursement from third party payors, including governmental payors (such as the Medicare and Medicaid programs in the U.S.), managed care organizations and private health insurers.
Our ability to operate successfully and manage our potential future growth depends significantly upon our ability to attract, retain, and motivate highly skilled and qualified research, technical, clinical, regulatory, sales, marketing, managerial and financial personnel. We compete for talent with numerous companies, as well as universities and non-profit research organizations.
We maintain a small executive team. Our ability to operate successfully and manage our potential future growth depends significantly upon our ability to attract, retain, and motivate highly skilled and qualified research, technical, clinical, regulatory, sales, marketing, managerial and financial personnel. We compete for talent with numerous companies, as well as universities and non-profit research organizations.
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.
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.
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.
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™.
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.
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.
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 in compliance with applicable laws and as required for submission to applicable regulatory bodies, including manufacturing, testing and validation of our RNL candidates; 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; and the degree to which our approved products are accepted in the marketplace.
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.
Before any new drugs may be introduced to the U.S. market, the manufacturer generally must obtain FDA approval through either an abbreviated new drug application (“ANDA”) process for generic drugs off patent that allow for bioequivalence to an existing reference listing drug (“RLD”) or the lengthier NDA process, which typically requires multiple successful and successive clinical trials to generate clinical data supportive of safety and efficacy along with extensive pharmacodynamic and pharmacokinetic preclinical testing to demonstrate safety.
Before any new drugs may be introduced to the U.S. market, the manufacturer generally must obtain FDA approval through either an ANDA process for generic drugs off patent that allow for bioequivalence to an existing RLD or the lengthier NDA process, which typically requires multiple successful and successive clinical trials to generate clinical data supportive of safety and efficacy along with extensive pharmacodynamic and pharmacokinetic preclinical testing to demonstrate safety.
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; 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; 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.
Without third party payor reimbursement, patients may not be able to obtain or afford prescribed medications. In addition, reimbursement guidelines and incentives provided to prescribing physicians by third party payors may have a significant impact on the prescribing physicians’ willingness and ability to prescribe our products.
Without third party payor reimbursement, patients may not be able to obtain or afford prescribed medications. In addition, coverage and reimbursement guidelines and restrictions set by third party payors may have a significant impact on the prescribing physicians’ willingness and ability to prescribe our products.
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.
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.
The timing of our clinical trials depends in part on the rate at which we can recruit patients to participate in clinical trials of our product candidates, and we may experience delays in our clinical trials if we encounter difficulties in enrollment.
Identifying and enrolling patients to participate in clinical trials of our product candidates is essential to our success. The timing of our clinical trials depends in part on the rate at which we can recruit patients to participate in clinical trials of our product candidates, and we may experience delays in our clinical trials if we encounter difficulties in enrollment.
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, 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 REYOBIQ™ and 188 RNL-BAM, and our CNSide TM Platform, as well as successfully defending our intellectual property against third-party challenges.
Significant adverse events may also lead regulatory authorities to require additional warnings on the label for such product, require us to conduct additional costly post-marketing studies, require us to develop a risk evaluation and mitigation strategy (“REMS”), among other possible requirements. If the product candidate has already been approved, such approval may be withdrawn.
Significant adverse events may also lead regulatory authorities to require additional warnings on the label for such product, require us to conduct additional costly post-marketing studies, require us to develop a REMS, among other possible requirements. If the product candidate has already been approved, such approval may be withdrawn.
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.
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.
In September 2020, the FDA granted both Orphan Drug designation and Fast Track designation to rhenium ( 186 Re) obisbemeda for the treatment of patients with GBM. In November 2021, the FDA granted Fast Track designation to rhenium ( 186 Re) obisbemeda for the treatment of patients with LM.
In September 2020, the FDA granted both orphan drug designation and Fast Track designation to REYOBIQ™ for the treatment of patients with GBM. In November 2021, the FDA granted Fast Track designation to REYOBIQ™ for the treatment of patients with LM.
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. This, in turn, would significantly adversely affect our business prospects.
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.
The manufacture of drug and device products for human use is subject to regulation and inspection from time to time by the FDA for compliance with the FDA’s cGMP, Quality System Regulations (“QSRs”), as well as equivalent requirements and inspections by state and non-U.S. 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 Quality System Regulation (“QSR”), as well as equivalent requirements and inspections by state and foreign. regulatory authorities.
Currently, this designation provides market exclusivity in the U.S. and the European Union for seven years and ten years, respectively, if a product is the first such product approved for such orphan indication.
Currently, this designation makes the product eligible for market exclusivity in the U.S. and the EU for seven years and ten years, respectively, if a product is the first such product approved for such orphan indication.
We may issue debt and equity securities or securities convertible into equity securities, any of which may be senior to our common stock as to distributions and in liquidation, which could negatively affect the value of our common stock. 48 In the future, we may attempt to increase our capital resources by entering into debt or debt-like financing that is unsecured or secured by up to all of our assets, or by issuing additional debt or equity securities, which could include issuances of secured or unsecured commercial paper, medium-term notes, senior notes, subordinated notes, guarantees, preferred stock, hybrid securities, or securities convertible into or exchangeable for equity securities.
In the future, we may attempt to increase our capital resources by entering into debt or debt-like financing that is unsecured or secured by up to all of our assets, or by issuing additional debt or equity securities, which could include issuances of secured or unsecured commercial paper, medium-term notes, senior notes, subordinated notes, guarantees, preferred stock, hybrid securities, or securities convertible into or exchangeable for equity securities.
Given, among other things, the current status of the capital markets and our recent stock price performance and financing strategies we may pursue may not be sufficient to fund our operations in the near term, there can be no assurances that we will be able to secure additional financing, or if available, that it will be sufficient to meet our needs or be on favorable terms.
Given, among other things, the current status of the capital markets, our recent stock price performance and the terms of our recent capital financings, there can be no assurances that we will be able to secure additional financing, or if available, that it will be sufficient to meet our needs or be on favorable terms.
We have generated negative cash flows from operations and have incurred net operating losses each year since we started business. For the year ended December 31, 2023, we incurred net losses of $13.3 million and our net cash used in operating activities was $12.9 million. As of December 31, 2023, our accumulated deficit was $480.5 million.
We have generated negative cash flows from operations and have incurred net operating losses each year since we started business. For the year ended December 31, 2024, we incurred net losses of $13.0 million and our net cash used in operating activities was $10.6 million. As of December 31, 2024, our accumulated deficit was $493.5 million.
Orphan drug designation may not ensure that we will enjoy market exclusivity in a particular market, and if we fail to obtain or maintain orphan drug designation or other regulatory exclusivity for some of our product candidates, our competitive position would be harmed. A product candidate that receives orphan drug designation can benefit from potential commercial benefits following approval.
Orphan drug designation may not ensure that we will enjoy market exclusivity in a particular market, and if we fail to obtain or maintain orphan drug designation or other regulatory exclusivity for some of our product candidates, our competitive position would be harmed.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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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, has over 25 years of experience addressing cybersecurity risks.
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.
As of the date of this report, we are not aware of any risks from cybersecurity threats, including as a result of any previous cybersecurity incidents, that have materially affected our business strategy, results of operations or financial condition or are reasonably 50 likely to have such a material effect.
As of the date of this report, we are not aware of any risks from cybersecurity threats, including as a result of any previous cybersecurity incidents, that have materially affected our business strategy , results of operations or financial condition or are reasonably likely to have such a material effect.
Our CFO oversees the ITFD and briefs our Board on cybersecurity matters, including the nature and design of our cybersecurity program, and threats, events, and program enhancements. Board Oversight While the Board has overall responsibility for risk oversight, the Board recently delegated to the audit committee of the Board the responsibility for assisting the Board with cybersecurity disclosure matters.
Our CFO oversees the ITFD and briefs our Board on cybersecurity matters, including the nature and design of our cybersecurity program, and threats, events, and program enhancements. Board Oversight While the Board has overall responsibility for risk oversight , the Board delegated to the audit committee of the Board the responsibility for assisting the Board with cybersecurity disclosure matters .
Our ITFD is responsible for the day-to-day management of the cybersecurity program, including the prevention, detection, investigation, response to, and recovery from cybersecurity threats and incidents, and is regularly engaged to help ensure the cybersecurity program functions effectively in the face of evolving cybersecurity threats.
Our 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.
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.
Such incident response team will include members of IT, finance (if applicable), legal, communications, human resources and any affected unit or department.
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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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Item 2. Pr operties We have one lease agreement for our San Antonio, Texas locations. The lease for this property will expire in February 2025. We also lease certain office space in Austin, Texas under a month-to-month operating lease agreement. We also have a lease agreement for office space in Charlottesville, Virginia.
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Item 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.
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We pay an aggregate of approximately $16,000 in rent per month for these properties. Item 3. Legal Proceedings None. Item 4. Mine Saf ety Disclosures Not applicable. 51 PART II
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Mine Saf ety Disclosures Not applicable. 58 PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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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 February 26, 2024, the Company had approximately four 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 21, 2025, the Company had approximately seventeen record holders of common stock.
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The information under the subheading “Equity Compensation Plan Information” under Item 12, Part III of this Form 10-K is incorporated herein by reference.
Added
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.
Removed
Purchases of Equity Securities by the Issuer and Affiliated Purchasers On October 31, 2023, the Company announced that its Board has approved a share repurchase program (the “Share Repurchase Program”), with authorization to repurchase up to $500,000 of the outstanding shares of the Company’s common stock.
Added
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
Removed
The Company intends to fund any repurchases under the Share Repurchase Program with available cash. The timing and amount of any shares repurchased will be determined based on the Company’s evaluation of market conditions and other factors, including consent of the Company’s lender. Repurchases may be made from time to time on the open market over through October 31, 2024.
Removed
During the year ended December 31, 2023, the Company purchased 78,559 of its common shares for approximately $126,000 as treasury stock. During the period January 1, 2024 through February 26, 2024, the Company purchased 168,015 of its common shares for approximately $340,000 as treasury stock.
Removed
The following table presents information with respect to purchases of common stock of the Company during the three months ended December 31, 2023: Period Total Number of Shares Purchased Average Price Paid per Share Total Number of Shares Purchased as Part of Publicly Announced Plans or Programs Maximum Number of Shares that May Yet Be Purchased Under the Plans or Programs (1) Approximate Dollar Value of Shares that May Yet Be Purchased Under the Plans or Programs October 1, 2023 - October 31, 2023 — $ — — — $500,000 November 1, 2023 - November 30, 2023 63,154 $1.59 63,154 251,311 $399,585 December 1, 2023 - December 31, 2023 15,405 $1.85 15,405 200,587 $371,086 Total 78,559 $1.72 78,559 200,587 $371,086 Item 6. [Reserved] 52

Item 7. Management's Discussion & Analysis

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

88 edited+79 added39 removed30 unchanged
Biggest changeThe following table summarizes the components of our research and development expenses for the years ended December 31, 2023 and 2022 (in thousands): Years ended December 31, 2023 2022 Research and development $ 9,624 $ 9,611 Share-based compensation 66 87 Total research and development expenses $ 9,690 $ 9,698 Research and development expenses for the year ended December 31, 2023 remained consistent with the same period in 2022, due to a decrease of $3.4 million in development of cGMP rhenium ( 186 Re) obisbemeda, a decrease of $1.9 million of professional and legal expenses, offset by a license agreement payment of $1.7 million to NanoTx Corp., from which we licensed our rhenium ( 186 Re) obisbemeda technology, resulting from the first patient treated in the GBM phase 2 trial and obligation to pay NanoTx 15% of CPRIT grant proceeds received (See Note 6 of the accompanying financial statements for more information), $3.0 million from treatment of patients for LM clinical trial in 2023, and $0.6 million increase of payroll expenses.
Biggest changeThe 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.
Financing Activities Net cash provided by financing activities for the year ended December 31, 2023 was primarily related to the net proceeds from sales of common stock of $5.2 million pursuant to the September 2022 Distribution Agreement with Canaccord and the 2022 Purchase Agreement with Lincoln Park, offset by $1.6 million of principal repayment under our Term Loan, and $0.1 million payment to purchase our common stock.
Net cash provided by financing activities for the year ended December 31, 2023 was primarily related to the net proceeds from sales of common stock of $5.2 million pursuant to the September 2022 Distribution Agreement with Canaccord and the 2022 Purchase Agreement with Lincoln Park, offset by $1.6 million of principal repayment under our Term Loan, and $0.1 million payment to purchase our common stock.
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.
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.
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 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 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 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.
In contrast, locally delivered and targeted radiopharmaceuticals that precisely deliver radiation in the form of beta particles such as Iodine-131 for thyroid cancer, are known to be safe and effective and minimize 54 exposure to normal cells and tissues especially with optimal administered dose and minimizing exposure to normal tissue.
In contrast, locally delivered and targeted radiopharmaceuticals that precisely deliver radiation in the form of beta particles such as Iodine-131 for thyroid cancer, are known to be safe and effective and minimize exposure to normal cells and tissues especially with optimal administered dose and minimizing exposure to normal tissue.
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.
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 63 years, with a median age of approximately nine years.
Alternatively, if we are not required to repay the funds, then payments received are recorded as revenue or contra-expense as the expenses are incurred. Deferred grant 62 liability represents grant funds received or receivable for which the allowable expenses have not yet been incurred as of the balance sheet date.
Alternatively, if we are not required to repay the funds, then payments received are recorded as revenue or contra-expense as the expenses are incurred. Deferred grant liability represents grant funds received or receivable for which the allowable expenses have not yet been incurred as of the balance sheet date.
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. We sold 150,000 shares under the Second Registration Statement.
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.
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 the Company from time to time, including, among others, market conditions, the trading price of the common stock and determinations by the Company 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 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.
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 drug 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.
Potential benefits of rhenium ( 186 Re) obisbemeda compared to standard external beam radiotherapy or EBRT include: The rhenium (186Re) obisbemeda radiation dose delivered to patients may be up to 20 times greater than what is possible with commonly used external beam radiation therapy (“EBRT”), which, unlike EBRT and proton beam devices, spares normal tissue and the brain from radiation exposure. Rhenium (186Re) obisbemeda can be visualized in real-time during administration, possibly giving clinicians better control of radiation dosing, distribution and retention. Rhenium (186Re) obisbemeda potentially more effectively treats a bulk tumor and microscopic disease that has already invaded healthy tissue. Rhenium (186Re) 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.
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.
Preclinical data from an ex vivo embolization experiment in which Technetium99m-BAM was intra-arterially delivered to a bovine kidney perfusion model was presented at the recent 2021 Society of Interventional Radiology Annual Scientific Meeting.
Preclinical data from an ex vivo embolization experiment in which Technetium99m-BAM was intra-arterially delivered to a bovine kidney perfusion model was presented at the Society of Interventional Radiology Annual Scientific Meeting.
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 (186Re) 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.
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.
Specifically, in 2022 we transferred the 188 RNL-BAM technology from UTHSA, and began planning to develop the drug 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 FDA IND submission. Our intended initial clinical target is liver cancer which is the sixth most common and third deadliest cancer worldwide.
In accordance with our accounting policy, we completed the annual evaluation for impairment of goodwill as of December 31, 2023 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, 2024 using the qualitative method and determined that no impairment existed.
General and administrative expenses 58 General and administrative expenses include costs for administrative personnel, legal and other professional expenses, and general corporate expenses.
General and administrative expenses General and administrative expenses include costs for administrative personnel, legal and other professional expenses, and general corporate expenses.
For grants outside the scope of ASC 808, we apply International Accounting Standards No. 20 ("IAS 20"), Accounting for Government Grants and Disclosure of Government Assistance, by analogy, and revenue is recognized when we incur expenses related to the grant for the amount we are entitled to under the provisions of the contract.
For grants outside the scope of ASC 808, we apply International Accounting Standards No. 20 (“IAS 20”), Accounting for Government Grants and Disclosure of Government Assistance, by analogy, and revenue is recognized when we incur expenses related to the grant for the amount we are entitled to under the provisions of the contract.
Our lead radiotherapeutic candidate, rhenium ( 186 Re) obisbemeda (formerly, 186 RNL”), 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.
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.
Critical Accounting Estimates The preparation of financial statements in conformity with accounting principles generally accepted in the United States 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.
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.
We expect aggregate research and development expenditures to increase significantly during 2024 as compared to the corresponding comparable period ended December 31, 2023, due to increased costs for the ReSPECT-LM clinical trial (for which CPRIT grant funding is 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 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.
Investing activities Net cash used in investing activities for the year ended December 31, 2023 was related to purchases of fixed assets of $0.2 million.
Net cash used in investing activities for the year ended December 31, 2023 was related to purchases of fixed assets of $0.1 million.
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 rhenium ( 186 Re) obisbemeda for the treatment of patients with LM through Phase 2 of the ReSPECT LM clinical trial.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Alignment with the FDA includes support of our proposed controls and release strategy for new drug substance and new drug product. Because this product is identical for recurrent GBM, LM, and PBC, we believe alignment will be consistent for rhenium ( 186 Re) obisbemeda used in other clinical development programs, including LM and PBC.
Alignment with the FDA includes support of our proposed controls and release strategy for new drug substance and new drug product. Because this product is identical for recurrent GBM, LM, and PBC, we believe alignment will be consistent for REYOBIQ™ used in other clinical development programs, including LM and PBC.
Even today, the treatment of GBM remains a significant challenge and it has been nearly a decade since the FDA approved a new therapy for this disease, and these more recent approvals have not improved GBM patients OS over past decades, and a significant unmet medical need persists.
Today, the treatment of GBM remains a significant challenge and it has been nearly a decade since the FDA approved a new therapy for this disease, and these more recent approvals have not improved the overall survival (“OS”) for GBM patients over past decades, and a significant unmet medical need persists.
The 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.
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.
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.
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.
On September 19, 2022, we entered into the CPRIT Contract, pursuant to which CPRIT will provide us with the CPRIT Grant of $17.6 million subject to the terms of the CPRIT Contract, to fund approximately two-thirds of the continued development of rhenium ( 186 Re) obisbemeda for the treatment of patients with LM.
CPRIT Grant On September 19, 2022, we entered into the CPRIT Contract, pursuant to which CPRIT will provide us with the CPRIT Grant of $17.6 million subject to the terms of the CPRIT Contract, to fund approximately two-thirds of the continued development of REYOBIQ™ for the treatment of patients with LM.
Grants and Awards In applying the provisions of Accounting Standards Codification (“ASC”) Topic 606, Revenue from Contracts with Customers (“ASC 606”), we have determined that government grants are out of the scope of ASC 606 because the funding entities do not meet the definition of a “customer”, as defined by ASC 606, as we do not consider there to be a transfer of control of goods or services.
Grants and Awards In applying the provisions of ASC Topic 606, Revenue from Contracts with Customers (“ASC 606”), we have determined that government grants are out of the scope of ASC 606 because the funding entities do not meet the definition of a “customer,” as defined by ASC 606, as we do not consider there to be a transfer of control of goods or services.
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.
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.
We have an accumulated deficit of $480.5 million as of December 31, 2023. Additionally, we used net cash of $12.9 million to fund our operating activities for the year ended December 31, 2023. These factors raise substantial doubt about our ability to continue as a going concern.
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.
On September 19, 2022, we entered into a Cancer Research Grant Contract (the “CPRIT Contract”), effective as of August 31, 2022, with Cancer Prevention and Research Institute of Texas (“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.
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.
Operating activities Net cash used in operating activities for the year ended December 31, 2023 was $12.9 million compared to $13.0 million in the same period of 2022.
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.
Rhenium ( 186 Re) obisbemeda is under clinical investigation in a multicenter, sequential cohort, open-label, volume and dose escalation study 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 (NCT01906385).
REYOBIQ™ is under clinical investigation in a Phase 1/2 multicenter, sequential cohort, open-label, volume and dose escalation study (“ReSPECT-GBM”) of the safety, tolerability, and distribution of REYOBIQ™ given by CED catheters to patients with recurrent or progressive malignant glioma after standard surgical, radiation, and/or chemotherapy treatment.
The following table summarizes the components of our share-based compensation expenses for the years ended December 31, 2023 and 2022 (in thousands): Years ended December 31, 2023 2022 Research and development $ 66 $ 87 General and administrative 503 519 Total share-based compensation $ 569 $ 606 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, 2023 and 2022.
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.
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 60 Agreement. The additional commitment fee may be paid in cash, common stock, or a combination thereof. We sold approximately 527,166 shares under the First Registration Statement.
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.
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 (“UTHSA”) to expand our tumor targeting capabilities and precision radiotherapeutics pipeline.
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.
Despite the best available medical treatments, the disease remains incurable. Even after efforts to manage the presenting signs and symptoms and completely resect the initial brain tumor, some microscopic disease almost always remains and tumor regrowth occurs within months. Approximately 90% or more of patients with primary GBM experience tumor recurrence.
Despite the best available medical treatments, the disease remains incurable. Even after efforts to manage the presenting signs and symptoms and completely resect the initial brain tumor, some microscopic disease almost always remains and tumor regrowth occurs within months.
The following table summarizes the general and administrative expenses for the years ended December 31, 2023 and 2022 (in thousands): Years ended December 31, 2023 2022 General and administrative $ 8,041 $ 9,719 Share-based compensation 503 519 Total general and administrative expenses $ 8,544 $ 10,238 General and administrative expenses decreased by approximately $1.7 million during the year ended December 31, 2023, as compared to the same period in 2022.
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.
We issued 410,500 shares under the 2022 Purchase Agreement for net proceeds of approximately $1.0 million from January 1, 2023 to December 31, 2023.
We issued 410,500 shares under the 2022 Purchase Agreement for net proceeds of approximately $1.0 million from January 1, 2023 to December 31, 2023. No shares of common stock were purchased under the 2022 Purchase Agreement during 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, 2023 and 2022 (in thousands): As of December 31, 2023 2022 Cash and cash equivalents $ 8,554 $ 18,120 Current assets $ 9,834 $ 21,817 Current liabilities 10,727 11,852 Working capital (deficit) $ (893 ) $ 9,965 We incurred net losses of $13.3 million for year ended December 31, 2023.
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.
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. In November 2021, the FDA granted Fast Track designation for rhenium ( 186 Re) obisbemeda for the treatment of LM.
In September 2020, the FDA granted both orphan drug designation and Fast Track designations to REYOBIQ™ for the treatment of patients with GBM.
To date, our operating losses have been funded primarily from outside sources of invested capital from issuance of our common and preferred stocks, proceeds from our Term Loan with Oxford and grant funding.
To date, our operating losses have been funded primarily from outside sources of invested capital from issuance of our common and preferred stocks, proceeds from our now-repaid in full term loan with Oxford Finance, LLC (“Oxford”), our line of credit facility with Pershing and grant funding.
For recurrent GBM, there are few currently approved treatments, which in the aggregate, provide only marginal survival benefit. Furthermore, these therapies are associated with significant side effects, which limit dosing and prolonged use.
There is no clear standard of care for recurrent GBM and the few currently approved treatments provide only marginal survival benefit and are associated with significant side effects, which limit dosing and prolonged use.
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.
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.
We have reached the capacity for sales of our shares under the September 2022 Distribution Agreement. On August 2, 2022, we entered into a purchase agreement (the “2022 Purchase Agreement”) and registration rights agreement pursuant to which Lincoln Park committed to purchase up to $50.0 million of shares of our common stock.
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.
We expect grant revenue will increase during 2024 and the remaining term of the CPRIT Grant through August 2025, as we continue to expand the LM clinical trial to add clinical sites and enroll patients.
The amounts recognized represent CPRIT’s share of the costs incurred for our REYOBIQ™ development for the treatment of patients with LM. We expect grant revenue will increase during the remaining term of the CPRIT Grant through August 2025, as we continue to expand the LM clinical trial to add clinical sites and enroll patients.
Our inability to raise additional cash would have a material and adverse impact on our operations and would cause us to default on our Term Loan.
Our inability to raise additional cash would have a material and adverse impact on our operations and ability to satisfy our obligations.
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.
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.
Initial clinical specimen processing and testing will begin in the first quarter 2024 in our ongoing Phase 1 ReSPECT-LM trial of rhenium ( 186 Re) obisbemeda in patients with LM. 56 ReSPECT-PBC Clinical Trial for Pediatric Brain Cancer The average annual age adjusted mortality rate for children aged 0-14 for malignant brain (and other CNS) tumors is 0.71/100,000, making it the most common cause of death and cancer death in this age group.
ReSPECT-PBC Clinical Trial for Pediatric Brain Cancer The average annual age adjusted mortality rate for children aged 0-14 for malignant brain (and other CNS) tumors is 0.71/100,000, making it the most common cause of death and cancer death in this age group.
Changes in these assumptions may lead to variability with respect to the amount of stock compensation expense we recognize related to stock options. Item 7A. Quantitative and Qualitat ive Disclosures About Market Risk Not applicable. 63
We have never declared or paid dividends on our common stock and have no plans to do so in the foreseeable future. 73 Changes in these assumptions may lead to variability with respect to the amount of stock compensation expense we recognize related to stock options. Item 7A. Quantitative and Qualitat ive Disclosures About Market Risk Not applicable. 74
As of December 31, 2023, the Company had approximately $8.6 million in cash and cash equivalents.
As of December 31, 2024, the Company had approximately $3.6 million in combined cash and cash equivalents and short-term investments.
The Phase 2b trial is expected to enroll up to 31 total patients with small- to medium-sized tumors and is targeted for full enrollment by the end of 2024, with the plan to add additional clinical sites to support the trial and an initial data read-out by the end of 2024.
Phase 2 of the trial is expected to enroll up to 34 total patients with small- to medium-sized tumors and is targeted for full enrollment by the end of 2025. We currently have four clinical sites, and expect a data read-out by the end of 2025.
The incidence of LM is growing and occurs in approximately 5%, or more, of people with late-stage cancer, or 110,000 people in the U.S. each year. It is highly lethal with an average one-year survival of just 7%. All solid cancers, particularly breast, lung, GI, and melanoma, have the potential to spread to the leptomeninges.
It is highly lethal with an average one-year survival of just 7%. All solid cancers, particularly breast, lung, GI, and melanoma, have the potential to spread to the leptomeninges.
The primary endpoint of the study is the incidence and severity of adverse events and dose limiting toxicities, together with determining the maximum tolerated and recommended Phase 2 dose. Full enrollment in the Phase 1 trial is expected by the end of 2024, with the plan to add additional clinical sites to support the trial.
The primary endpoint of the study is the incidence and severity of adverse events and dose limiting toxicities, together with determining the maximum tolerated and recommended Phase 2 dose. Full enrollment in the Phase 1 trial was achieved at the end of 2024, and we announced the trial completion on February 26, 2025.
Overview Plus Therapeutics is a U.S. pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for CNS cancers. Our novel radioactive drug formulations 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.
Overview Plus Therapeutics is a U.S. pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (“CNS”) cancers. Our novel radioactive drug formulations and medical devices and therapeutic candidates are designed to deliver safe and effective doses of radiation to tumors.
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 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.
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.
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 amounts recognized represents CPRIT’s share of the costs incurred for our rhenium (186Re) obisbemeda development for the treatment of patients with LM. As of December 31, 2023, we had $1.9 million of deferred revenue related to the CPRIT Grant.
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.
Since the initial FDA feedback and receiving important adult GBM data and experience with rhenium ( 186 Re) obisbemeda and follow-up communications with the FDA, we plan to submit a pediatric brain tumor IND to investigate the use of rhenium ( 186 Re) obisbemeda in two pediatric brain cancers, high-grade glioma and ependymoma, in the first or second quarter of 2024.
Given the initial FDA feedback, receipt of adult GBM data and experience with REYOBIQ™ and follow-up communications with the FDA, we submitted a pediatric brain tumor IND for our ReSPECT-PBC clinical trial to investigate the use of REYOBIQ™ in two pediatric brain cancers, high-grade glioma and ependymoma, in the fourth quarter of 2024.
The FDA indicated agreement with our proposed application of cGMP guidance for radiotherapeutics, small molecule drug products and liposome drug products for our novel rhenium ( 186 Re) obisbemeda in support of ongoing and future GBM clinical trials, manufacturing scale up, and commercialization.
On August 29, 2022, we announced feedback from a Type C meeting with the FDA regarding Chemistry, Manufacturing and Controls practices. The FDA indicated agreement with our proposed application of cGMP guidance for radiotherapeutics, small molecule drug products and liposome drug products for REYOBIQ™ in support of ongoing and future GBM clinical trials, manufacturing scale up, and commercialization.
In August 2021, we announced plans for treating pediatric brain cancer at the 2021 American Association of Neurological Surgeons Annual Scientific Meeting. In July 2021, we reported that we had received FDA feedback pertaining to a pre-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.
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, we initiated the trial and began screening patients for the ReSPECT-LM Phase 1 clinical trial in Q4 2021.
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.
We received $7.1 million of the available funding under the CPRIT Grant during 2022 and 2023, of which we recognized $4.9 million and $0.2 million of grant revenue during the years ended December 31, 2023 and 2022, respectively.
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 grant revenue receivable as of December 31, 2024.
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.
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.
Impairment of Goodwill We perform our goodwill impairment analysis at the reporting unit level. For the years ended December 31, 2023 and 2022, 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, 2024 and 2023, our company has one reporting unit.
We received $7.1 million of the available funding under the CPRIT Grant during 2022 and 2023, of which we recognized $4.9 million and $0.2 million of grant revenue during the years ended December 31, 2023 and 2022, respectively.
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.
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. 53 On August 29, 2022, we announced feedback from a Type C meeting with the FDA regarding Chemistry, Manufacturing and Controls (“CMC”) practices.
National Institutes of Health/National Cancer Institute which is expected to provide financial support for 60 the continued clinical development of REYOBIQ™ for recurrent GBM through the completion of a Phase 2 clinical trial, including enrollment of up to 55 patients.
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.
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.
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. Our headquarters and manufacturing facilities are in Texas and are in proximity to world-class cancer institutions and researchers.
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.
We cannot sell more shares than registered under the Second Registration Statement under the 2022 Purchase Agreement without registering additional shares. During the period from August 17, 2022 to December 31, 2022, we issued 266,666 shares under the 2022 Purchase Agreement for net proceeds of approximately $3.2 million.
As a result of the March 2025 Private Placement, until March 4, 2026, we are unable to utilize the 2022 Purchase Agreement without the consent of investors in that offering. During the period from August 17, 2022 to December 31, 2022, we issued 266,666 shares under the 2022 Purchase Agreement for net proceeds of approximately $3.2 million.
Net cash used in investing activities for year ended December 31, 2022 was primarily related to cash payments of $0.5 million made for purchases of fixed assets and intangible assets, and $0.3 million paid for in-process research and development.
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.
In addition, we are obligated to make operating lease payments for our office and laboratory space, and we may be required to make payments under certain of our other contractual agreements. 61 Other than as described above, we have no purchase commitments or long-term contractual obligations , except for lease obligations as of December 31, 2023.
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 Income (Expense) The following table summarizes interest income, interest expense, and other income and expense for the years ended December 31, 2023 and 2022 (in thousands): Years ended December 31, 2023 2022 Interest income $ 400 $ 147 Interest expense (395 ) (711 ) Change in fair value of liability instruments 1 Total $ 5 $ (563 ) The decrease in interest expense for the year ended December 31, 2023 as compared to the same period in 2022 was primarily due to reduced debt principal as the Company continued to pay down its term loan.
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.
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 .
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.
Interim results showed that a single treatment with rhenium ( 186 Re) obisbemeda showed a consistent decreased cerebrospinal fluid (“CSF”) tumor cell count/ml and was very well tolerated by all LM patients.
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.

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