OS Therapies Inc 10-K

Item 1. Business. Overview and Mission OS Therapies Incorporated (“OS Therapies,” the “Company,” “we,” “our” or “us”) is a clinical stage biopharmaceutical company focused on the identification, development and commercialization of treatments for Osteosarcoma (OS) and other solid tumors. Our mission is to address the significant need for new treatments in cancers of the bone in children and young adults. Osteosarcoma is an extremely challenging and often aggressive cancer that has particular treatment challenges due to its location, changing genotypes and high recurrence rates. We are currently seeking to answer the call for new treatments with our lead core product candidate OST-HER2 (also known as OST31-164). We intend to expand our pipeline beyond Osteosarcoma with this product candidate into other solid tumors with the same recurrence mechanism of action, including breast, esophageal and lung cancers. With the addition of our OST-Tunable Drug Conjugate (OST-tADC) platform, which we consider to be a next generation antibody-drug conjugate (ADC) technology, we will be targeting ovarian, lung and pancreatic cancers. “Tunable” is a term used in drug development that refers to the properties that can be influenced by chemical modifications, and “antibody-drug conjugate” or ADC is a term used to describe a drug made up of a monoclonal antibody attached to a cytotoxic payload, or a highly active and toxic pharmaceutical molecule, through chemical linkers. The ADC links an antibody that can home in on a targeted tumor like and deploy the cytotoxic payload or toxic agent against the tumor. Furthering our founding mission, we also intend to investigate clinical indications for OST-tADC in Osteosarcoma. We believe that there have not been any new treatments approved by the U.S. Food and Drug Administration (FDA) for Osteosarcoma for more than 40 years. In humans, Osteosarcoma is an extremely rare cancer that primarily affects children, teenagers and young adults generally under 40 years of age. We are not aware of any competing adjuvant therapy for Osteosarcoma to be tested in children that is further along in the development process than OST-HER2. This disease is difficult to diagnose. The standard of care following first line therapies is simply to screen and wait for possible recurrence/metastasis, or the development of secondary malignant growths at a distance from a primary site of cancer. Studies published in the Journal of Clinical Oncology, “Osteosarcoma Relapse After Combined Modality Therapy: An Analysis of Unselected Patients in the Cooperative Osteosarcoma Study Group (COSS),” by Kempf-Bielack B., et al. (January 2005), and “Second and Subsequent Recurrences of Osteosarcoma: Presentation, Treatment, and Outcomes of 249 Consecutive Cooperative Osteosarcoma Study Group Patients,” by Bielack S., et al. (February 2009), reported that recurrence/metastasis happens in approximately half of all patients within 12 to 18 months following initial remittance. For those patients that experience recurrence, metastasis is typically to the lungs and brain, with survival rates of approximately 13% over the next year, according to these studies. Pipeline of Our Product Candidates We have built a pipeline of product candidates targeting multiple indications for solid cancers. Our pipeline includes two drug technologies: (i) OST-HER2, an off-the-shelf immunotherapy, which is a type of cancer treatment that helps one’s immune system fight cancer, comprised of a genetically weakened and modified strain of Listeria monocytogenes , a species of bacteria that causes the infection listeriosis, that expresses HER2 peptides, and (ii) OST-tADC, a next generation tunable ADC with a plug-and-play platform that features tunable pH sensitive silicone linkers (SiLinkers). The payloads may include antibodies, chemotherapeutics, cytotoxins and potentially mRNA treatments directly into and in the vicinity of solid tumors. OST-HER2 (OST31-164). Our most advanced product candidate, OST-HER2, is a genetically engineered strain of Listeria monocytogenes , attenuated for reduced virulence, increased antibiotic susceptibility and the expression of three HER2 protein epitopes fused to immune-enhancing peptides on the membrane of the bacteria. OST-HER2 has received an orphan drug designation in the United States. The FDA may designate a biologic product as an orphan product if it is intended to treat a rare disease or condition, which generally is defined as having a patient population of fewer than 200,000 individuals in the United States. Osteosarcoma has an incidence rate of new cases of approximately 1,000 individuals affected per year in the United States. Orphan product designation, subject to limited exceptions, can provide a period of market exclusivity for a product that is the first to receive marketing approval for the designated indication. Other potential indications may include breast, esophageal, lung and other solid tumors. In August 2021, OST-HER2 was awarded rare pediatric disease designation and previously received fast track designation by the FDA. In May 2024, we submitted a request to the FDA for breakthrough therapy designation for OST-HER2. Such designations by the FDA do not convey any advantages or shorten the duration of the regulatory review or approval process. 2 OST-tADC. Our tunable drug conjugate (tADC) platform is currently in preclinical development. Each tADC contains four main components: ligand, payload cassette adaptor, linker and payload. In addition, tADCs contain units to optimize physicochemical properties. The ligands are selected to bind to receptors overexpressed on cancer cells. Upon binding, the tADC construct gets internalized into the cancer cell, where the payload is released, to cause cell death. The payload cassette adaptors enable the stoichiometrical attachments of linkers and payloads. The SiLinkers represent a novel and pH-sensitive linker system. The SiLinker release profile can be tuned with proximal functional groups, resulting in payload release in the endosome, lysosome or the slightly acidic tumor microenvironment. The SiLinker system is compatible with a variety of payloads and not limited to the employment of cytotoxic drug delivery. The first set of internal programs focus on the use of SiLinker and conditionally active payloads (CAPs™) drug products. CAPs are cytotoxic drugs which on their own, due to their functional groups, cannot readily permeate cells at physiological pH; however, at the slightly acidic pH of the tumor-microenvironment, after some linker cleavage, these payloads readily permeate into cancer cells, resulting in an enhanced bystander effect. Our lead program targets folate receptor alpha, a protein expressed on the surface of cells that participates in cell signaling, as well as cellular replication and division, and is overexpressed in multiple cancers such as ovarian and endometrial cancers. The lead compound employs folic acid, a small molecule, as the targeting ligands and contains six exatecan-silanols, which is a type of silanol-based cytotoxic payload, as payloads. This discovery work is being carried out at Syngene International Limited, an integrated contract research organization (CRO) based in Bangalore, India. From time to time, we may evaluate collaboration opportunities for our product candidates. We expect to work opportunistically with pharmaceutical and biotechnology companies, as we have done with BlinkBio, Inc. by in-licensing the OST-tADC technology, seeking to utilize our technology and know-how for developing additional oncologic drug products. The following table summarizes information regarding our product candidates and development programs. In addition to our development of OST-HER2 for multiple indications of solid cancers in humans, OST-HER2 is a product candidate for veterinary use in canines. As part of our growth strategies, we intend to consider potentially out-licensing OST-HER2 to animal health companies for such use. See “ OS-Focused Clinical Trials and Studies — Preclinical Animal Study ” for more information. Our Pending Acquisition of HER2 and Lm -Related Assets On January 28, 2025, we entered into an Asset Purchase Agreement (the “HER2 Purchase Agreement”) with Ayala Pharmaceuticals, Inc., a Delaware corporation formerly known as Advaxis, Inc. (“Ayala”), pursuant to which we agreed, subject to the terms and conditions set forth therein, to acquire from Ayala Lm -based immuno-oncology programs and related intellectual property assets (collectively, the “HER2 Assets”). The HER2 Assets include two investigational new drug (IND) filings with the FDA: (i) ADXS-503 for non-small cell lung cancer; and (ii) ADXS-504 for prostate cancer. The closing of the transaction, which we expect to in the second quarter of 2025, is subject to assignment of a license between Ayala and the Trustees of the University of Pennsylvania (the “Penn License”), execution and delivery of a patent assignment agreement, a termination of license agreement, a lock-up agreement and a registration rights agreement, the approval of the transaction by Ayala stockholders and other customary closing conditions. 3 Our OS-Focused Clinical Trials and Studies We and our licensors have conducted a number of clinical trials and studies in the field of Osteosarcoma and Tunable Drug Conjugates to date. Phase IIb Clinical Trial. In July 2021, a Phase IIb clinical trial to treat Osteosarcoma in humans was commenced and sponsored by us and conducted by George Clinical, Inc., our clinical research services provider, utilizing our OST-HER2 product candidate. The course of the trial involved a regimen of 16 infusions of OST-HER2 administered over 48 weeks to 41 eligible patients from ages 12 to 39 years. As of September 30, 2024, the treatment phase of the trial has been completed, and patients are now being followed for long-term survival. This Phase IIb trial was conducted at major hospitals across 21 sites in 18 states. On January 15, 2025, we announced that our Phase IIb clinical trial achieved its primary endpoint with statistical significance. The primary outcome measures were the relative proportion of patients experiencing event-free (recurrence-free) survival at 12 months (“Responders”) compared to the best available historical control group from U.S. published literature (the “Published Control”) by evaluating the patients for recurrence every 3 months, consistent with the standard of care. Trial results showed that 33% of OST-HER2 treated patients were Responders compared to 20% in the Published Control. The secondary outcome measures were overall survival of patients for three years compared to the three-year overall survival of the Published Control, which will be evaluated by assessing patients every three months over the course of three years, and the incidence of treatment-emergent adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) Grade 5, the safety of which will be assessed throughout the treatment period of 48 weeks with assessments of potential persistence of the vector every three months and continuing for three years after treatment. CTCAE is a method to categorize adverse events across all clinical trials of five grades, with Grade 5 being death. Trial results showed a higher proportion of OST-HER2 treated patients were alive at the 12-month (91% vs. 80%) and 24-month (61% vs. 40%) post-resection timepoints relative to the Published Control. Notably, 100% of patients who were disease-free at 12 months remained alive at 12, 18, 24, and 30 months at their last follow-up. OST-HER2 was well tolerated with a safety profile supportive of regulatory approval; no treatment-emergent adverse events classified as CTCAE Grade 5 (death) were observed. We believe the efficacy results, combined with the favorable safety profile and the unmet clinical need, support the potential for regulatory approval. We plan to request a Type B or Type C FDA meeting in the first quarter of 2025 to discuss the data and the path to a BLA. Subject to positive FDA feedback, we plan to submit a BLA with the FDA CBER for approval to market the drug candidate in the second quarter of 2025. The FDA generally takes six to ten months to complete its review of a BLA, subject to any FDA request for additional information. We believe that it remains uncertain whether a Phase III clinical trial will be necessary for the advancement of OST-HER2 through the regulatory approval process. We will not know whether a Phase III trial will be required until we receive a determination from the FDA following the filing of a BLA for marketing approval as to whether the results of our ongoing Phase IIb trial provided sufficiently positive endpoint data. Phase Ib Clinical Trial. From September 2015 to May 2017, a Phase Ib trial to treat Osteosarcoma in humans was sponsored and conducted by Advaxis utilizing ADXS-HER2 (also known as ADXS31-164), the patents of which we agreed to purchase from Ayala to develop and commercialize our lead core product candidate, OST-HER2. The Phase Ib was a multicenter, open-label, dose-escalation study designed to estimate the maximum tolerated dose (MTD) and determine the recommended Phase II dose of ADXS-HER2. The trial was conducted at hospitals in Colorado, Michigan, North Carolina, Pennsylvania and Texas. The course of the trial involved injecting 12 adult patients with HER2 expressing solid tumors with escalating doses of ADXS-HER2 every three weeks during a 12-week treatment cycle. Following the last dose of study treatment, all 12 patients participated in a three-year Listeria monocytogenes surveillance period. 4 The primary outcome measures were the number of patients with dose-limiting toxicities for each dose level as assessed by the CTCAE Grade 4 (time frame: four months), with Grade 4 being life threatening, and the frequency and severity of adverse effects as assessed by CTCAE Grade 4 (time frame: three years). The secondary outcome measures were (i) proportion of patients who have objective tumor response (complete or partial) evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and RECIST-based immune criteria (ir-RECIST) and (ii) changes in clinical immunology based upon serum, which were measured and evaluated by collection of peripheral blood for preparation of peripheral blood mononuclear cells and serum at baseline, prior to each treatment and post-treatment in the first treatment cycle only. The results of this study were primarily intended to describe the safety and tolerability of ADXS-HER2. This study was not intended to contribute to the evaluation of the effectiveness of ADXS-HER2 for the treatment of patients with a history of HER2 expressing tumors. Overall, the data presented from this Phase Ib trial demonstrated that ADXS-HER2 IV infusion at the dose of 1×10 9 CFU appeared to be well tolerated in 12 subjects treated and evaluable with no evidence of dose-limiting toxicities. No objective tumor responses (complete or partial) were observed in this late stage, heavily pre-treated patient cohort. Based on the data presented, the recommended Phase II dose of ADXS-HER2 was determined to be 1x10 9 CFU as it was well tolerated. Preclinical Animal Study. From July 2012 to September 2015, a preclinical study to treat Osteosarcoma in 18 companion canines (sometimes referred to as a Phase I animal trial) was sponsored and conducted by a previous licensee of Advaxis utilizing ADXS-HER2, the product candidate of Advaxis, from whom we agreed to purchase patents for ADXS-HER2 constructs that enable us to develop OST-HER2. The results showed, in the setting of minimal residual disease where there is a very small number of cancer cells remaining in the body during or after initial treatment, significant improvements in overall survival and metastatic disease progression when compared to an historical control group with Human Epidermal Growth Factor Receptor 2-positive (HER2) appendicular Osteosarcoma, a well-recognized spontaneous model for pediatric Osteosarcoma, treated with amputation and chemotherapy alone. In September 2016, the study results, published in the journal, Clinical Cancer Research, “Immunotherapy with a HER2-Targeting Listeria Induces HER2-Specific Immunity and Demonstrates Potential Therapeutic Effects in a Phase I Trial in Canine Osteosarcoma,” by Mason, N. et al. ( https://pubmed.ncbi.nlm.nih.gov/26994144/ ), indicated that ADXS-HER2 significantly increased the duration of survival time and one-, two- and three-year survival rates and significantly reduced the incidence of metastatic disease (the spread of cancer cells from an initial or primary site to a different or secondary site within the host’s body) when compared with the historical control group. The overall survival rates at one, two and three years for dogs treated with ADXS-HER2 were 77.8%, 67% and 56%, respectively, compared to 55%, 28% and 22%, respectively, for the historical control group. The median survival time (MST) for the historical control group was 423 days, which was significantly shorter than the 956 days for ADXS-HER2 — treated dogs (p=0.014, HR 0.33; 95% confidence intervals; CI, 0.136 – 0.802). The study also noted the important translational relevance of the findings for children with Osteosarcoma. This study for canine Osteosarcoma indications constituted preclinical work as it relates to our development of OST-HER2 to treat Osteosarcoma in humans. In analyzing preclinical study results, a p-value is used to determine the probability as to whether the difference between two data sets is due to chance. The smaller the p-value, the more likely the differences are not due to chance alone. In general, if the p-value is less than or equal to 0.05, the outcome is considered statistically significant. The FDA’s evidentiary standard of efficacy generally relies on a p-value of less than or equal to 0.05. A p-value greater than 0.05 is considered statistically non-significant. As shown above, the results of this preclinical study were statistically significant compared to the historical control group. Following the study, an application for the use of ADXS-HER2, our OST-HER2, in the treatment of canine Osteosarcoma was submitted to the USDA. In December 2017, ADXS-HER2 was granted a conditional license by the USDA. Because we are the current licensee of ADXS-HER2 constructs, we held the conditional license previously granted to ADXS-HER2 for OST-HER2. The conditional license allowed for commercialization but limited the use of OST-HER2 to treat dogs, one year of age and older, diagnosed with Osteosarcoma. We allowed such conditional license to lapse as a result of improvements made in our manufacturing process that would improve the performance in canines, and we plan to request from USDA a new conditional license for the product once we have contracted for manufacture with a suitable USDA licensed contract manufacturer. To receive full licensure, the USDA requires the submission of additional data that further describes the effects of OST-HER2 on metabolism and shedding in canines and provides substantial evidence of the safety, purity, potency and effectiveness of OST-HER2. We are currently evaluating the best path to development. Preclinical Development. Our OST-HER2 product candidate for breast, esophageal, lung and other solid tumor indications is currently in preclinical development. Whether additional preclinical trials will be required will depend on several factors, including the outcome of our ongoing Phase IIb clinical trial, the inclusion or exclusion of breast, esophageal, lung or other solid tumor indications in any follow-on study, or master protocol, to the Phase IIb clinical trial and the FDA’s determination of whether the preclinical data is sufficient to support the safety and efficacy of the drug. Although we cannot be certain, we believe that OST-HER2 may not require additional preclinical development before progressing to human clinical trials for breast, esophageal, lung and other solid tumor indications if the results of our ongoing Phase IIb clinical trial have sufficiently positive endpoint data as determined by the FDA. 5 Our OST-tADC product candidate for all indications is also currently in preclinical development. We will need to conduct further preclinical trials for OST-tADC prior to the submission of an IND in order to pursue clinical trials with these candidates. Such preclinical trials are expected to include pharmacokinetics and pharmacodynamics, two-week dose finding toxicology studies in vivo (on living cell lines or in living animals), as well as good laboratory practice (GLP) trials ensuring stability, potency and purity of the IND product candidate. Our Technology Platform We are in the process of building a fully integrated platform technology to accelerate the development of a range of product candidates across multiple therapeutic areas. Our platform technology is intended to leverage our management’s in-depth experience in immunotherapy research, development and manufacturing to enable us to pursue multiple therapeutic targets. Our scientists and scientific advisors have accumulated decades of collective experience in the field of immunotherapy, oncology and small-molecule drug production, contributing key insights and significant achievement in our clinical development process. Our Growth Strategies Our goal is to enrich and lengthen the lives of patients by being a leading, fully integrated biotechnology company. We are seeking to develop, manufacture and commercialize multiple product candidates targeting orphan and non-orphan oncologic diseases across multiple tissue types and therapeutic areas. To achieve our goal, we are pursuing the following growth strategies: ● Consider potentially out-licensing OST-HER2 to animal health companies for veterinary use to treat dogs diagnosed with Osteosarcoma, one year of age or older. ● Obtain marketing approval for OST-HER2 in Osteosarcoma, then quickly pivot to a master protocol within breast, esophageal, lung and other solid tumors where metastases express HER2 that could be targeted by immune cells. ● Conclude pre-clinical and toxicology trials with the lead drug candidate for OST-tADC (OST-tADC-A, Exatecan-silanol-FRa), and file for an IND to initiate a Phase I trial in ovarian cancer and other folate receptor alpha overexpressing cancers like endometrial cancer and some osteosarcomas. We believe that positive results from preclinical two-week and good laboratory practice (GLP) toxicology studies may also stimulate potential out-licensing activity of SiLinker and CAPs drug products, while not limiting therapeutic development. ● Establish global commercial and medical affairs capabilities for OST-HER2 based therapies. Expansion Opportunities We believe opportunities may exist from time to time to expand our current business through acquisitions or in-licenses of complementary products or technologies or acquisitions of companies with complementary products or technologies. While we have current collaborative agreements in place, we believe in an opportunistic approach to collaboration and licensing; thus, we expect to operate in a manner that is customary in the pharmaceutical industry, including potential acquisitions and partnerships. We are also aware of increased acquisition and licensing interest from large pharmaceutical firms in biotechnology companies developing ADC technology as a relatively new kind of cancer therapy. In the article, “Seagen Cancer Therapy Draws Suitors” (March 7, 2023), The Wall Street Journal reported that driving this interest, according to analysts, is the potential for ADCs to capture a chunk of the worldwide cancer market. Technical advances by combining the ADCs with widely used cancer agents like immunotherapies have also opened up exploring various potential cancer applications, according to the article. 6 Our Scientific Collaborations Scientific Collaborators. We collaborate with experts and physicians to help advance our programs and, together, we are focused on translational strategies to support the clinical study of our new therapy candidates. These collaborations support our goals to translate deep expertise in structure-based drug design into a novel portfolio of precisely targeted therapies. We strive to address medical needs for patients with cancer harboring resistance mutations in driver kinases using technology originally developed at the University of Pennsylvania under the guidance of Dr. Robert G. Petit, our Chief Medical and Scientific Officer. Our partnering approach with physician-scientists allows us to understand the limitations of existing therapies, which we believe will lead to product candidates that address the dual needs of treatment resistance and kinase selectivity. OST-HER2’s compositions and methods of use are covered by three granted U.S. utility patents and one granted Japanese patent that we in-license through our development license and supply agreement with Advaxis and were developed at the University of Pennsylvania and are owned by the University of Pennsylvania, either jointly with Advaxis or solely by the University. See “ Our Licensing Agreements — Advaxis ” and “ Our Intellectual Property ” below. We have also established collaborations through service agreements with global CROs to provide scale and expertise in research chemistry, chemical manufacturing, biology, pharmacology and toxicology, and clinical studies. Scientific Advisory Board. We have established a scientific advisory board comprised of seven members with extensive experience in the field of oncology. Our scientific advisors include researchers who publish widely cited research on topics relevant to the study and treatment of cancer, lead clinical units at experienced precision medicine cancer centers in the United States and are actively involved in our drug development process and programs. Our scientific advisory board meets periodically with our board of directors and management to discuss matters relating to our business activities and to establish commercial business alliances. Members of our scientific advisory board are reimbursed by us for out-of-pocket expenses incurred in connection with serving on our advisory board. Our scientific advisory board currently includes the following physicians and their professional affiliations: ● Nabil M. Ahmed, MD — Texas Children’s Hospital ● Peter M. Anderson, MD — Cleveland Clinic ● Doug S. Hawkins, MD — Seattle Children’s Hospital ● Meenakshi Hedge, MD — Texas Children’s Hospital ● Alejandro Sweet-Cordero, MD — University of California San Francisco ● Brenda Weigel, MD — Masonic Cancer Center — University of Minnesota ● Felasfa M. Wodajo, MD — Inova Fairfax Hospital, Virginia Patient Advocacy Advisory Board. We have established a patient advocacy advisory board comprised of four members with experience dealing with the effects of Osteosarcoma. This board is responsible for reviewing and establishing our patient advocacy philosophy and policy. This board also develops procedures for patient care evaluation while adhering to regulatory standards. This board identifies gaps in patient care and represents patient interests at FDA meetings, ensuring that patient voices are heard in regulatory discussions. Members of our patient advocacy advisory board are reimbursed by us for out-of-pocket expenses incurred in connection with serving on such board and sign customary non-disclosure agreements. Our patient advocacy advisory board currently includes the following individuals and their affiliations: ● Miriam Cohen — Founding Member, Chairperson and President of Osteosarcoma Collaborative ● Olivia Egge — Founding Member, Counsel and Patient Advocate of Osteosarcoma Collaborative; Graduate student at Columbia University School of Professional Studies; Osteosarcoma Survivor ● Mac Tichenor — President of Osteosarcoma Institute ● Tony Trent — President of The Tyler Trent Foundation 7 ADC Advisory Board. We have established an ADC advisory board comprised of two members with extensive experience with ADC technologies. This board is responsible for reviewing and establishing our strategy and policies related to ADCs and helps to design and implement procedures for evaluating the efficacy and safety of our ADC technologies, ensuring compliance with regulatory standards. This board identifies opportunities to enhance ADC technology and address challenges in development, contributing to the advancement of innovative therapies in the field. Members of our ADC advisory board are reimbursed by us for out-of-pocket expenses incurred in connection with serving on such board and sign customary non-disclosure agreements. Our ADC advisory board currently includes the following professionals and their affiliations: ● Borys Shor, Ph.D. — President and Chief Executive Officer of Manhattan BioSolutions, Inc. ● Jutta Wanner, Ph.D. — Senior Vice President of Drug Discovery at Alpha-9 Oncology, Inc. Some of the members of our advisory boards may serve as consultants under consulting agreements for which they will receive compensation. To date, however, none of our advisory board members has served as consultants to us, and we have not entered into any consulting agreements with any of them. To our knowledge, none of our advisory board members has any conflict of interest between their obligations to us and their obligations to others. Hospitals, medical centers and companies with which advisory board members are involved may in the future have commercial relationships with us. Our Licensing Agreements Advaxis. In November 2020, we entered into an amended and restated development, license and supply agreement with Advaxis, pursuant to which Advaxis granted a license to us that allows us to utilize Advaxis’ ADXS-HER2 construct patents to develop and commercialize ADXS-HER2, our lead product candidate (OST-HER2). On January 28, 2025, we entered into the HER2 Purchase Agreement with Ayala, pursuant to which we agreed, subject to the terms and conditions set forth therein, to acquire from Ayala the HER2 Assets. The closing of the transaction, which we expect to occur in the second quarter of 2025, is subject to assignment of the Penn License, execution and delivery of a patent assignment agreement, a termination of license agreement, a lock-up agreement and a registration rights agreement, the approval of the transaction by Ayala stockholders and other customary conditions. BlinkBio. In August 2020, we entered into a licensing agreement with BlinkBio, Inc., pursuant to which BlinkBio granted a license to us that allows us to utilize BlinkBio’s proprietary technology to develop, manufacture and commercialize certain of our products. BlinkBio granted us an exclusive license for tADC’s that are directed towards, binds to or modifies the folate receptor alpha and a co-exclusive license for tADC’s that are directed towards, binds to or modifies any target other than the folate receptor alpha, such as HER2. In connection with the license agreement, we also agreed to issue a convertible note to BlinkBio. See “ Management’s Discussion and Analysis of Financial Condition and Results of Operations ” for more information on our licensing agreements and the BlinkBio convertible note. Our Research Services Agreement George Clinical. In June 2020, we entered into a services agreement, as amended, with George Clinical, Inc., a clinical contract research organization. Pursuant to this agreement, we engaged George Clinical to use its clinical research services for our study entitled “An Open Label, Phase 2 Study of Maintenance Therapy with OST-HER2 after Resection of Recurrent Osteosarcoma.” See “ Management’s Discussion and Analysis of Financial Condition and Results of Operations ” for more information on our research services agreement with George Clinical. Our Intellectual Property Our commercial success depends in part on our ability and the ability of those third parties from whom we in-license patents to obtain and maintain intellectual property protection in the United States and other countries for our current or future product candidates, including our lead core product candidate OST-HER2, our other core product candidate OST-tADC, our non-core product candidates, our proprietary compound library and other know-how. We seek to protect our proprietary and intellectual property position by, among other methods, in-licensing patents and patent applications in the United States and abroad related to our proprietary technology, inventions and improvements that are important to the development and implementation of our business. We also rely on trade secrets, know-how and continuing technological innovation to develop and maintain our proprietary and intellectual property position. 8 Although we have agreed to acquire the HER2 Assets pursuant to the HER2 Purchase Agreement, we do not currently own any issued patents. We in-license patents and patent applications related to our lead core product candidate OST-HER2 from Advaxis, Inc. and our other core product candidate OST-tADC from BlinkBio, Inc. The intellectual property licensed from Advaxis, Inc. includes nine granted U.S. utility patents and a number of foreign patents and pending patent applications. The patents and patent applications if granted are expected to expire between 2030 and 2035, not including any patent term extension. The intellectual property licensed from BlinkBio, Inc. includes six granted U.S. utility patents and a number of foreign patents and pending patent applications. The patents cover methods of use of silicon based drug conjugates and silanol based therapeutic payloads. The patents and pending patent applications if granted are expected to expire between 2036 and 2037, not including any patent term extension. We also rely on trade secrets and know-how relating to our proprietary technology and product candidates and continuing innovation to develop, strengthen and maintain our proprietary position in the field of oncology. Our future plans also include reliance on data exclusivity, market exclusivity and patent term extensions when available. The degree of patent protection we require to successfully commercialize our current or future product candidates may be unavailable or severely limited in some cases and may not adequately protect our rights or permit us to gain or keep any competitive advantage. We cannot provide any assurances that any of the patents that we in-license have, or that any of such pending patent applications that mature into issued patents will include, claims with a scope sufficient to protect OST-HER2 and OST-tADC or our other current or future product candidates. In addition, if the breadth or strength of protection provided by such patent applications or any patents we may in-license is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates. Our ability to stop third parties from making, using, selling, offering to sell or importing products identical or similar to ours will depend on the extent to which we have rights under valid and enforceable patents, trade secrets or other intellectual property rights that cover these activities. The patent rights of biotechnology and pharmaceutical companies like ours are generally uncertain and can involve complex legal, scientific and factual issues. Our and any future licensor’s current and future patent applications may not result in the issuance of any patent in any particular jurisdiction, and the claims of any current or future issued patents, even if those claims are valid and enforceable, may not provide sufficient protection from competitors. Any owned or in-licensed patent rights we may obtain may not enable us to prevent others from replicating, manufacturing, using or administering our product candidates for any indication. Moreover, the coverage initially claimed in a patent application may be significantly reduced before a patent is issued, and a patent’s scope can be reinterpreted after issuance. In addition, any patent we may own or in-license may be challenged, circumvented or invalidated by third parties. As a result, we cannot ensure that any of our product candidates will be protected by valid and enforceable patents. See “ Risk Factors — Risks Related to Our Intellectual Property ” for a more comprehensive description of risks related to our intellectual property. Our Commercialization Strategy We intend to retain significant development and commercial rights to our product candidates and, if marketing approval is obtained, to commercialize our product candidates on our own, or potentially with a partner, in the United States and other regions. We currently have no sales, marketing or commercial product distribution capabilities. We intend to build the necessary infrastructure and capabilities over time for the United States, and potentially other regions, following further advancement of our product candidates. We believe that such a focused sales and marketing organization will be able to address the community of oncologists who are the key specialists in treating the patient populations for which our product candidates are being developed. Clinical data, the size of the addressable patient population and the size of the commercial infrastructure and manufacturing needs may all influence or alter our commercialization plans. The responsibilities of the marketing organization would include developing educational initiatives with respect to approved products and establishing relationships with researchers and practitioners in relevant fields of medicine. 9 Our Future Manufacturing We do not own or operate, and currently have no plans to establish, any manufacturing facilities. We rely, and expect to continue to rely, on third parties for the manufacture of our product candidates for preclinical and clinical testing, as well as for commercial manufacturing if any of our product candidates obtain marketing approval. We also rely, and expect to continue to rely, on third parties to package, label, store and distribute our investigational product candidates, as well as our commercial products if marketing approval is obtained. We believe that this strategy allows us to maintain a more efficient infrastructure by eliminating the need for us to invest in our own manufacturing facilities, equipment, and personnel while also enabling us to focus our expertise and resources on the development of our product candidates. All of our product candidates are biopharmaceuticals and are manufactured in synthetic processes from available starting materials. The chemistry appears amenable to scale-up and does not currently require unusual equipment in the manufacturing process. We expect to continue to develop product candidates that can be produced cost-effectively at contract manufacturing facilities. Currently, the OST-HER2 active pharmaceutical ingredients (API) (e.g., clinical drug substance) are manufactured in accordance with GMPs. The drug product formulation is being developed with the goal of producing lyophilized therapeutics with consistent and immediate release dissolution profiles that can be reproducibly manufactured using automated equipment. All manufacturing activities for the OST-HER2 drug product are performed in accordance with GMPs. We currently rely on these vendors as single-source contract manufacturing organizations. We are in the process of developing our supply chain for each of our product candidates and intend to put in place framework agreements under which third party ReciBioPharma, a chemical manufacturer, will generally provide us with necessary quantities of API and drug product on a project-by-project basis based on our development needs. As we advance our product candidates through development, we will explore adding backup suppliers for the OST-tADC and drug product for each of our product candidates to protect against any potential supply disruptions. We generally expect to rely on third parties for the manufacture of any companion diagnostics that we may develop. Government Regulation Our current or future product candidates and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, distribution, import and export are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States and by comparable authorities in other countries. Preclinical Studies and IND The preclinical developmental stage generally involves laboratory evaluations of drug chemistry, formulation and stability, as well as studies to evaluate toxicity in animals, which support subsequent clinical testing. The sponsor must submit the results of the preclinical studies, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND. An IND is a request for authorization from the FDA to administer an investigational product to humans, and must become effective before human clinical trials may begin. Preclinical studies include laboratory evaluation of product chemistry and formulation, as well as in vitro and animal studies to assess the potential for adverse events and in some cases to establish a rationale for therapeutic use. The conduct of preclinical studies is subject to federal regulations and requirements, including GLP regulations for safety/toxicology studies. An IND sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature, and plans for clinical trials, among other things, to the FDA as part of an IND. Some long-term preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, may continue after the IND is submitted. An IND automatically becomes effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to one or more proposed clinical trials and places the trial on clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to commence. 10 Clinical Trials Clinical trials must be conducted: (i) in compliance with federal regulations; (ii) in compliance with good clinical practice (“GCP”) an international standard intended to protect the rights and health of patients and to define the roles of clinical trial sponsors, investigators, and monitors; and (iii) under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated. Clinical trials are typically conducted at geographically diverse clinical trial sites and are designed to permit the FDA to evaluate the overall benefit-risk relationship of the drug and to provide adequate information for the labeling of the drug when considering whether a drug satisfies the statutory standard for commercialized. Clinical trials must be approved in the United States by an Institutional Review Board (“IRB”), an appropriately constituted group that has been formally designated to review and monitor biomedical research involving human subjects and which has the authority to approve, require modifications in, or disapprove research to protect the rights, safety and welfare of the human research subject. In other countries, clinical trials may be subject to review and approval by ethics boards similar to IRBs. The FDA may order the temporary, or permanent, discontinuation of a clinical trial at any time, or impose other sanctions, if it believes that the clinical trial either is not being conducted in accordance with the FDA requirements or presents an unacceptable risk to the clinical trial patients. An IRB may also require the clinical trial it has approved to be halted, either temporarily or permanently, for failure to comply with the IRB’s requirements, or may impose other conditions or sanctions. The FDA’s current good manufacturing practices (cGMPs) apply to drug product candidates in Phase II and Phase III clinical trials; thus, the product candidates in those trials must be manufactured in compliance with cGMPs. Marketing Approval Before we can commercialize any of our current or future product candidates, we must obtain marketing approval. We have not received approval to market any of our current product candidates. We expect to rely on third-party CROs and/or regulatory consultants to assist us in this process. Securing regulatory approval requires the submission of extensive preclinical and clinical data and supporting information to the various regulatory authorities for each therapeutic indication and line of treatment to establish the product candidate’s safety and efficacy. Securing regulatory approval also requires the submission of information about the drug manufacturing process to, and further requires inspection of manufacturing facilities by, the relevant regulatory authority. The process required by the FDA before biopharmaceuticals may be marketed in the United States generally involves the following: ● nonclinical laboratory and, at times, animal tests; ● adequate and well-controlled human clinical trials to establish the safety and efficacy of the proposed drug for its intended use or uses; ● pre-approval inspection of manufacturing facilities and some clinical trial sites; and ● FDA approval of an NDA or a BLA, which must occur before a drug or biologic product can be marketed or sold. We are not permitted to market our current or future product candidates until we receive approval of a BLA from the FDA CBER in the United States or a marketing authorization application from the European Medicines Agency in the European Economic Area or until we receive approval of comparable agencies in other foreign countries. 11 Post-Market Requirements If the FDA or a comparable foreign regulatory authority approves any of our current or future product candidates, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for the drug will be subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMPs and Good Clinical Practices (“GCPs”) for any clinical trials that we conduct post-approval. Any regulatory approvals that we receive for our current or future product candidates may also be subject to limitations on the approved indicated uses for which the drug may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase IV clinical trials, and surveillance to monitor the safety and efficacy of the drug. Later discovery of previously unknown problems with a drug, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things: ● restrictions on the marketing or manufacturing of the drug, withdrawal of the drug from the market, or drug recalls; ● fines, warning or other letters or holds on clinical trials; ● refusal by the FDA to approve pending applications or supplements to approved applications filed by us, or suspension or revocation of drug license approvals; ● drug seizure or detention, or refusal to permit the import or export of drugs; and ● injunctions or the imposition of civil or criminal penalties. In order to produce our product candidates for clinical trials and our products, if any, for commercial purposes, either at our own facility or at a third-party’s facility, we and our third party vendors will need to comply with the FDA’s cGMP regulations and guidelines. As part of our ongoing quality and process improvement efforts, we conducted a gap analysis of our cGMP quality system and it identified certain key areas for necessary remediation, including with regard to documentation requirements. We are subject to inspections by the FDA and comparable foreign regulatory authorities to confirm compliance with applicable regulatory requirements. Animal Health Products Certain U.S. federal regulatory agencies are charged with oversight and regulatory authority of animal health products in the United States. These agencies, depending on the product and its intended use, may include the FDA, the U.S. Department of Agriculture (“USDA”) and the U.S. Environmental Protection Agency (“EPA”). The FDA Center for Veterinary Medicine (“CVM”) regulates animal pharmaceuticals under the Food, Drug and Cosmetics Act. The EPA is responsible for regulating pesticides, which include some products used for controlling pests and diseases in animals. U.S. Department of Agriculture . The regulation of veterinary biologics is overseen by the USDA, specifically the USDA Animal and Plant Health Inspection Service (“APHIS”) and the USDA Center for Veterinary Biologics (“CVB”). The APHIS and CVB are responsible for regulating veterinary vaccines and some biologics pursuant to the Virus-Serum-Toxin Act. The APHIS is responsible for protecting animal health by regulating the importation, interstate movement and environmental release of veterinary biologics. This includes overseeing the importation and exportation of veterinary biologics, issuing permits for the movement of these products across state lines, and regulating the release of genetically engineered veterinary biologics into the environment. The CVB is responsible for ensuring the safety, purity, potency and efficacy of veterinary biologics, including vaccines, diagnostics, and other biologics used in animals. The CVB evaluates the safety and efficacy of these products before granting them approval for use in animals. The CVB also oversees the manufacturing, testing, labeling and distribution of veterinary biologics and monitors their ongoing safety and effectiveness. 12 USDA Center for Veterinary Biologics. The CVB reviews and approves applications for veterinary biologics, including vaccines, immunomodulators, diagnostic kits and other biologic products. The CVB evaluates the safety, efficacy and quality of each product and grants licenses for products that meet the necessary regulatory requirements. The licensure process for veterinary biologics involves several key steps, including: ● Pre-License Evaluation. Before a veterinary biologic can be licensed, the manufacturer must submit an application to the CVB. The CVB reviews the application and evaluates the data on the product’s safety, efficacy and quality. This evaluation may include laboratory studies, field studies and other relevant information. ● Licensing Decision. Based on its evaluation, the CVB may grant a license for the product or require additional data or studies before making a final decision. If the CVB determines that the product meets all necessary regulatory requirements, it grants a license for the product. ● Labeling. Once a product is licensed, the manufacturer must submit labeling for the product to the CVB for approval. The labeling must include specific information on the product’s indications, dosage, administration, contraindications and warnings. ● Manufacturing Standards. The CVB establishes and enforces manufacturing standards for veterinary biologics, including requirements for facilities, equipment and procedures. The CVB conducts inspections of manufacturing facilities to ensure compliance with these standards and may revoke licenses for manufacturers that fail to comply. ● Post-Licensure Surveillance. The CVB monitors veterinary biologics after they are licensed to detect and respond to any safety or efficacy issues that may arise. The CVB may require manufacturers to conduct post-licensure surveillance studies or to report adverse events associated with their products. Conditional licenses are used to meet an emergency condition, limited market, local situation or other special circumstance. A product may be granted a conditional license if it has demonstrated a reasonable expectation of efficacy and safety, but additional data is needed to fully evaluate its efficacy and safety. To be eligible for conditional licensure, a veterinary biologic must meet certain regulatory criteria, including: ● the product must be intended for use in a target species for which there is a significant need; ● the product must have demonstrated a reasonable expectation of efficacy and safety based on preclinical and/or field studies; ● the product must have an acceptable safety profile; and ● the manufacturer must submit a plan for follow-up studies to address the data gaps or uncertainties identified during the evaluation process. A product with conditional licensure can be marketed and sold, but it must be labeled with specific conditions, such as limitations on use, required follow-up studies and other specific instructions for use. The product label must also clearly state that the product has been conditionally licensed and that additional data is required to fully evaluate its efficacy and safety. The manufacturer must continue to collect data on the safety and efficacy of the product and submit it to the CVB for review. The CVB may require additional studies or data to be submitted before granting full licensure. To obtain full licensure for a veterinary biologic product that has been granted conditional licensure by the CVB, the manufacturer must meet the follow-up study requirements specified in the conditional license and submit additional data to the CVB demonstrating the safety and efficacy of the product, which may include results from additional studies, post-marketing surveillance data and other relevant information. In addition to granting licenses, the CVB is responsible for establishing and enforcing manufacturing standards for veterinary biologics, including requirements for facilities, equipment, and procedures. The CVB conducts inspections of manufacturing facilities to ensure compliance with these standards and may revoke licenses for manufacturers that fail to comply. The CVB also monitors veterinary biologics after they are marketed to detect and respond to any safety or efficacy issues that may arise. The CVB may require manufacturers to conduct post-marketing surveillance studies or to report adverse events associated with their products. 13 Other Healthcare Laws Although we do not currently have any drugs on the market, if we begin commercializing our current or future product candidates, we will be subject to additional healthcare statutory and regulatory requirements and enforcement by the federal government and the states and foreign governments in which we conduct our business. Healthcare providers, including physicians, play a primary role in the recommendation and prescription of any current or future product candidates for which we obtain marketing approval. Our future arrangements with healthcare providers, as well as third-party payors and other customers, may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute our current or future product candidates for which we obtain marketing approval. Restrictions under applicable federal and state healthcare laws and regulations, include the following: Anti-Kickback Statute. The Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under federal and state healthcare programs such as Medicare, Medicaid and TRICARE. False Claims Act. The False Claims Act imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government. In addition, manufacturers can be held liable under the False Claims Act even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. The government may assert that a claim including items and services resulting from a violation of the federal Anti-Kickback Statute constitutes a false of fraudulent claim for purposes of the False Claims Act. Analogous State Laws. Analogous state laws and regulations, such as state anti-kickback and false claims laws that may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers; and some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other health care providers or marketing expenditures. Healthcare Reform The United States and many foreign jurisdictions have enacted or proposed legislative and regulatory changes affecting the healthcare system. Changes in regulations, statutes or the interpretation of existing regulations could impact our business in the future by requiring, for example, (i) changes to our manufacturing arrangements, (ii) additions or modifications to product labeling, (iii) the recall or discontinuation of our products or (iv) additional record-keeping requirements. If any such changes were to be imposed, they could adversely affect the operation of our business. In the United States, there have been and continue to be a number of legislative initiatives to contain healthcare costs. For example, in March 2010, the Affordable Care Act, or the ACA, was passed, which substantially changed the way healthcare is financed by both governmental and private insurers, and significantly impacted the U.S. pharmaceutical industry. The ACA, among other things, subjects biological products to potential competition by lower-cost biosimilars, addresses a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increases the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extends the rebate program to individuals enrolled in Medicaid managed care organizations, establishes annual fees and taxes on manufacturers of certain branded prescription drugs, and creates a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 70% (increased pursuant to the Bipartisan Budget Act of 2018, effective as of 2019) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D. There has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices. Specifically, there have been several recent U.S. Congressional inquiries and proposed federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs. In May 2019, CMS issued a final rule to allow Medicare Advantage Plans the option of using step therapy, a type of prior authorization, for Part B drugs beginning January 1, 2020. This final rule codified CMS’s policy change that was effective January 1, 2019. 14 On September 24, 2020, the FDA released a final rule effective November 30, 2020, providing guidance for states to build and submit importation plans for drugs from Canada. The Inflation Reduction Act (“IRA”) was passed into law on August 16, 2022. The drug pricing reform section of the IRA represents a sweeping change with respect to how the Medicare program will pay for prescription drugs in the future. The IRA drug pricing provisions will be phased in by 2029. Medicare will negotiate a “maximum fair price” directly with manufacturers for the most expensive drugs covered under Medicare Part B and Medicare Part D. In addition, additional rebates will be imposed on manufacturers related to certain Medicare Part B and D covered drugs to the extent their costs are rising faster than inflation. In addition, the Part D benefit will be restructured and in 2025 the existing coverage gap discount program, in which manufacturers must agree to offer 70% (increased pursuant to the Bipartisan Budget Act of 2018, effective as of 2019) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D will sunset. The program will be replaced by a new Part D rebate program pursuant to which manufacturers of certain drugs will pay a rebate of 10 percent off the negotiated price for applicable drugs (branded drugs and biologics manufactured by companies that have Part D discount agreements) after the deductible is satisfied through the catastrophic phase of the benefit. In the catastrophic phase, manufacturers will provide a 20 percent discount off negotiated price. At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to designed to create prescription drug price transparency and in some instances control pharmaceutical and biological product pricing or set maximum reimbursement for certain drug products, and, in some cases, designed to encourage importation from other countries and bulk purchasing. In addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other health care programs. These measures could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing. There have been, and likely will continue to be, legislative and regulatory proposals at the foreign, federal and state levels directed at broadening the availability of healthcare and containing or lowering the cost of healthcare. Privacy and Data Protection Laws HIPAA. The federal Health Insurance Portability and Accountability Act of 1996 (“HIPPA”) imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services; similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. HITECH. HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”) and its implementing regulations, which also imposes obligations on certain covered entity healthcare providers, health plans, and healthcare clearinghouses as well as their business associates that perform certain services involving the use or disclosure of individually identifiable health information, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions. GDPR. The EU General Data Protection Regulation (“GDPR”) also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR. In addition, the GDPR includes restrictions on cross-border data transfers. The GDPR may increase our responsibility and liability in relation to personal data that we process where such processing is subject to the GDPR, and we may be required to put in place additional mechanisms to ensure compliance with the GDPR, including as implemented by individual countries. Compliance with the GDPR is a rigorous and time-intensive process that may increase our cost of doing business or require us to change our business practices, and despite those efforts, there is a risk that we may be subject to fines and penalties, litigation, and reputational harm in connection with our European activities. Further, the United Kingdom’s decision to leave the European Union, referred to as Brexit, has created uncertainty with regard to data protection regulation in the United Kingdom. In particular, it is unclear how data transfers to and from the United Kingdom will be regulated now that the United Kingdom has left the European Union. 15 CCPA. California recently enacted and has proposed companion regulations to the California Consumer Privacy Act (“CCPA”) which went into effect January 1, 2020. The CCPA creates new individual privacy rights for California consumers (as defined in the law) and places increased privacy and security obligations on entities handling personal data of consumers or households. The CCPA requires covered companies to provide certain disclosures to consumers about its data collection, use and sharing practices, and to provide affected California residents with ways to opt-out of certain sales or transfers of personal information. As of March 28, 2020, the California State Attorney General has proposed varying versions of companion draft regulations which are not yet finalized. Despite the delay in adopting regulations, the California State Attorney General will commence enforcement actions against violators beginning July 1, 2020. While there is currently an exception for protected health information that is subject to HIPAA and clinical trial regulations, other records and information we maintain on our customers may be subject to the CCPA. Where state laws are more protective than HIPAA, we must comply with the state laws we are subject to, in addition to HIPAA. In certain cases, it may be necessary to modify our planned operations and procedures to comply with these more stringent state laws. Not only may some of these state laws impose fines and penalties upon violators, but also some, unlike HIPAA, may afford private rights of action to individuals who believe their personal information has been misused. In addition, state laws are changing rapidly, and there is discussion of a new federal privacy law or federal breach notification law, to which we may be subject. Environmental Regulations Our operations, properties and products are subject to a variety of U.S. and foreign environmental laws and regulations governing, among other things, use of manufacturing components containing substances below established threshold, air emissions, wastewater discharges, management and disposal of hazardous and non-hazardous materials and waste and remediation of releases of hazardous materials. Our operations involve the use of hazardous and flammable materials, including chemicals and biological and radioactive materials. Our operations also produce hazardous waste products. We generally contract with third parties for the disposal of these materials and wastes. The use of hazardous substances is regulated and monitored by various environmental regulatory authorities such as the EPA. As such, we are subject to national, state and local laws, regulations and directives pertaining to hazardous substances, pollution and protection of the environment, health and safety, which govern, among other things, emissions to the air, discharges onto land or waters, the maintenance of safe conditions in the workplace, and the generation, handling, storage, transportation, treatment and disposal of waste materials. These laws include, without limitation, the Comprehensive Environmental Response, Compensation, and Liability Act, the Federal Facilities Compliance Act, the Hazardous Materials Transportation Act, and the Resource Conservation and Recovery Act. Pricing Regulations and Third-Party Coverage and Reimbursement The regulations that govern regulatory approvals, pricing and reimbursement for new drugs vary widely from country to country. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. As a result, we might obtain marketing approval for a product candidate in a particular country, but then be subject to price regulations that delay our commercial launch of the product candidate, possibly for lengthy time periods. Our ability to commercialize any current or future product candidates successfully also will depend in part on the extent to which coverage and reimbursement for these current or future product candidates and related treatments will be available from government authorities, private health insurers and other organizations. Government authorities and other third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. Factors payors consider in determining reimbursement are based on whether the product is: ● a covered benefit under its health plan; ● safe, effective and medically necessary; ● appropriate for the specific patient; ● cost-effective; and ● neither experimental nor investigational. 16 A primary trend in the U.S. healthcare industry and elsewhere is cost containment. Government authorities and other third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular drugs. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for drugs. Reimbursement may impact the demand for, or the price of, any product candidate for which we obtain marketing approval. There may be significant delays in obtaining reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the FDA or similar regulatory authorities outside the United States. Moreover, eligibility for reimbursement does not imply that any drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States. In the United States, the principal decisions about coverage and reimbursement of new medicines under the Medicare program are typically made by the Centers for Medicare & Medicaid Services (“CMS”) an agency within the U.S. Department of Health and Human Services, or HHS. CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. Trade Laws Among other matters, U.S. and foreign anti-corruption, anti-money laundering, export control, sanctions, and other trade laws and regulations, which are collectively referred to as Trade Laws, prohibit companies and their employees, agents, clinical research organizations, legal counsel, accountants, consultants, contractors, and other partners from authorizing, promising, offering, providing, soliciting, or receiving directly or indirectly, corrupt or improper payments or anything else of value to or from recipients in the public or private sector. Violations of Trade Laws can result in substantial criminal fines and civil penalties, imprisonment, the loss of trade privileges, debarment, tax reassessments, breach of contract and fraud litigation, reputational harm, and other consequences. We have, or may have in the future, direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities, and other organizations. We plan to engage third parties for clinical trials and/or to obtain necessary permits, licenses, patent registrations, and other regulatory approvals and we can be held liable for the corrupt or other illegal activities of our personnel, agents, or partners, even if we do not explicitly authorize or have prior knowledge of such activities. Our Competition While we are not aware of any competing adjuvant therapy for Osteosarcoma to be tested in children that is further along in the development process than OST-HER2, there are a large number of companies developing or marketing treatments for rare diseases and cancers, including many major pharmaceutical and biotechnology companies. We may face competition from other product candidates in development for these indications, including product candidates in development from AstraZeneca, Y-mAbs Therapeutics and MD Anderson Cancer Center, among others. Human Capital and Employees As of March 28, 2025, we had four full-time employees and one part-time employee. We also utilize the services of a limited number of consultants as needed to perform specialized regulatory and medical-related services. Our employees are not represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good. All of our employees have entered into agreements with our company requiring them not to disclose our proprietary information and assigning to us all rights to inventions made during their employment. 17 Facilities Our corporate address is 115 Pullman Crossing Road, Suite 103, Grasonville, Maryland 21638. This space is the accounting office of our Chief Financial Officer and provided to us rent free. We believe that suitable additional or alternative space would be available in the future on commercially reasonable terms, if necessary. As of the date of this annual report, all our operations are conducted remotely. Recent Developments On December 24, 2024, we entered into a Securities Purchase Agreement (the “Purchase Agreement”) with certain institutional and accredited investors (collectively, the “PIPE investors”), substantially all of whom were our existing stockholders, pursuant to which we agreed to issue and sell to the PIPE investors immediately separable units (the “Units”), with each Unit being comprised of (i) one share of Series A Senior Convertible Preferred Stock, par value $0.001 per share (the “Series A Preferred Stock”), and (ii) a warrant to purchase one share of common stock (each, a “Series A Warrant” and such shares, the “Warrant Shares”), at a price per Unit of $4.00, for aggregate gross proceeds of not less than $6 million and not more than $10 million (the “Private Placement”). At two closings occurring on December 31, 2024 and January 14, 2025, we issued to the PIPE investors an aggregate of (i) 1,775,750 shares of Series A Preferred Stock and (ii) Series A Warrants initially exercisable into 1,775,750 shares of common stock. The gross proceeds from the Private Placement, before deducting transaction fees and other estimated Private Placement expenses, were approximately $7,103,000. The Purchase Agreement requires us to seek stockholder approval for any transactions contemplated by the Purchase Agreement and the related documents for which the rules of the NYSE American require stockholder approval (“Stockholder Approval”) and to hold a special meeting of stockholders for the purpose of obtaining Stockholder Approval not later than April 10, 2025. In the event Stockholder Approval is not obtained at the first meeting, we are required to call a meeting every four months seeking Stockholder Approval until Stockholder Approval is obtained. Brookline Capital Markets, a division of Arcadia Securities, LLC (“Brookline”), acted as exclusive placement agent for the issuance and sale of the securities in the Private Placement. Pursuant to the terms of a letter agreement, dated December 27, 2024, between us and Brookline (the “Placement Agency Agreement”), we agreed to pay Brookline an aggregate cash fee (the “Cash Fee”) equal to (i) 7% of the gross proceeds received by us from the sale of the securities in the Private Placement to PIPE investors other than certain PIPE investors identified on a schedule thereto (“Reduced Fee Purchasers”), plus (ii) 3% of the gross proceeds received by us from the sale of the securities in the Private Placement to Reduced Fee Purchasers, plus expenses; provided that Ceros Financial Services, Inc., Brookline’s selected dealer for the Private Placement (“Ceros”), is entitled to 33.3% of the Cash Fee. In addition, we agreed to pay Brookline or its designees a fee in the form of warrants to purchase shares of common stock (the “Agent Warrants”). The Agent Warrants are initially exercisable into a number of shares of common stock equal to (i) 7% of the number of shares of common stock initially issuable pursuant to the shares of Series A Preferred Stock issued to PIPE investors, other than Reduced Fee Purchasers in the Private Placement, plus (ii) 3% of the number of shares of common stock initially issuable pursuant to the shares of Series A Preferred Stock issued to Reduced Fee Purchasers in the Private Placement; provided that Ceros or its designee is entitled to 33.3% of the Agent Warrants. At two closings occurring on December 31, 2024 and January 14, 2025, (i) Brookline received an aggregate cash fee of $159,685 and the right to receive Agent Warrants initially exercisable for an aggregate of 39,918 shares of common stock, and (ii) Ceros received an aggregate cash fee of $79,723 and the right to receive Agent Warrants initially exercisable for an aggregate of 19,930 shares of common stock. On January 28, 2025, we entered into the HER2 Purchase Agreement with Ayala, pursuant to which we agreed, subject to the terms and conditions set forth therein, to acquire from Ayala the HER2 Assets. The HER2 Assets include two IND filings with the FDA: (i) ADXS-503 for non-small cell lung cancer; and (ii) ADXS-504 for prostate cancer. The closing of the transaction, which we expect to occur in the second quarter of 2025, is subject to assignment of the Penn License, execution and delivery of a patent assignment agreement, a termination of license agreement, a lock-up agreement and a registration rights agreement, the approval of the transaction by Ayala stockholders and other customary closing conditions. Other Information We were formed as a Delaware limited liability company on April 12, 2018 under the name OS Therapies, LLC. On June 24, 2019, we converted from a limited liability company to a Delaware corporation and changed our name to OS Therapies Incorporated. We completed our initial public offering in August 2024 and our common stock is currently listed on NYSE American under the symbol “OSTX.” We presently conduct all of our operations remotely. Our registered corporate address is 115 Pullman Crossing Road, Suite #103, Grasonville, Maryland 21638, and our telephone number is (410) 297-7793. Our website address is www.ostherapies.com. We make available on this website, free of charge, our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and amendments to those reports pursuant to Section 13(a) or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish such information to, the SEC. Reports and other information we file with the SEC may also be viewed at the SEC’s website at www.sec.gov. The information contained on, or that can be accessed through, our website is not incorporated by reference into this report. 18