EMA rolling review advances OS Therapies (NYSE: OSTX) rare cancer therapy
Rhea-AI Filing Summary
OS Therapies filed an 8-K describing major regulatory progress for its lead immunotherapy OST-HER2 in recurrent, fully resected pulmonary metastatic osteosarcoma. The European Medicines Agency has begun a rolling review of a Conditional Marketing Authorisation application, using 3-year overall survival as the key endpoint.
The company expects updated 2.5-year overall survival data by mid–second quarter 2026 and 3-year data early in the fourth quarter of 2026, with a potential EMA decision in the fourth quarter of 2026. OS Therapies is also engaging regulators in the U.K., Australia and the U.S. and plans a global confirmatory Phase 3 trial to start in the third quarter of 2026.
Management highlights that peak European sales for OST-HER2 could exceed $300 million annually, with more than $50 million in sales beginning in 2027 if approvals are obtained. OST-HER2 holds multiple special designations, and a future U.S. Biologics License Application could make the company eligible for a Priority Review Voucher that it intends to sell.
Positive
- EMA rolling review and aligned global Phase 3 design for OST-HER2 mark a significant regulatory milestone, with the company targeting Conditional Marketing Authorisations across Europe, the U.K. and Australia and an accelerated U.S. BLA pathway, directly supporting its lead asset’s de‑risking and value potential.
Negative
- None.
Insights
EMA rolling review and multi-region paths materially advance OST-HER2’s de-risking and revenue potential.
The filing shows OST-HER2 has entered EMA rolling review for a Conditional Marketing Authorisation, anchored on 3-year overall survival data. OS Therapies has aligned with European and Australian regulators on a global confirmatory Phase 3 design, a key step toward potential early market access in several regions.
Management explicitly frames commercial upside, citing potential peak European sales above $300 million annually and more than $50 million in sales starting in 2027, contingent on approvals. OST-HER2’s orphan, fast track, rare pediatric disease and advanced therapy designations, plus potential Priority Review Voucher proceeds, collectively strengthen the program’s strategic value, though outcomes still depend on forthcoming survival data and regulator decisions.
8-K Event Classification
Key Figures
Key Terms
Conditional Marketing Authorisation regulatory
Rolling Review regulatory
Biologics License Application regulatory
Priority Review Voucher regulatory
Orphan Drug Designation regulatory
Advanced Therapy Medicinal Product designation regulatory
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SECURITIES AND EXCHANGE COMMISSION
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FORM
CURRENT REPORT
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CURRENT REPORT ON FORM 8-K
OS Therapies Incorporated
April 30, 2026
Item 7.01. Regulation FD Disclosure.
On April 30, 2026, OS Therapies Incorporated (the “Company”) issued a press release announcing, among other things, that the European Medicines Agency has initiated a rolling review (continuous evaluation) of the Company’s regulatory dossier for OST-HER2 and providing an update on certain other regulatory interactions and related Company developments. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
On April 30, 2026, the Company also held a conference call to review OST-HER2 immune pharmacodynamic biomarker response (seroconversion) data and to review regulatory updates relating to the OST-HER2 program. A copy of the slide presentation that was used during the conference call is furnished as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.
The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibits 99.1 and 99.2, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, and shall not be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
Cautionary Note Regarding Forward-Looking Statements
This report, including Exhibits 99.1 and 99.2, contains forward-looking statements within the meaning of the federal securities laws. Forward-looking statements include statements regarding the Company’s expectations, plans, prospects, anticipated timing of regulatory interactions, anticipated timing and outcomes of regulatory review processes, anticipated clinical and regulatory milestones, anticipated commercialization and market access opportunities, anticipated sales and other financial or operating expectations, and other statements that are not historical facts. Words such as “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “might,” “plan,” “potential,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
Forward-looking statements are based on management’s current expectations and assumptions as of the date of this report and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others, risks and uncertainties related to regulatory processes and outcomes, the timing and results of clinical trials and data analyses, the Company’s ability to obtain and maintain regulatory approvals, authorizations, designations, and reimbursement, the Company’s ability to execute its development and commercialization strategy and other risks and uncertainties described in the Company’s filings with the Securities and Exchange Commission (the “SEC”), including under the heading “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and other filings the Company may make with the SEC from time to time. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove to be incorrect, actual results may vary materially from those indicated or anticipated by these forward-looking statements. Therefore, you should not rely on any of these forward-looking statements.
The forward-looking statements included in this report are made only as of the date of this report, and except as otherwise required by applicable securities law, the Company assumes no obligation, nor does the Company intend to publicly update or revise any forward-looking statements to reflect subsequent events or circumstances.
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Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
| Exhibit Number |
Description | |
| 99.1 | Press Release issued by OS Therapies Incorporated on April 30, 2026. | |
| 99.2 | Slide Presentation dated April 30, 2026. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). |
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SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| OS THERAPIES INCORPORATED | |||
| Dated: April 30, 2026 | By: | /s/ Paul A. Romness, MPH | |
| Name: | Paul A. Romness, MPH | ||
| Title: | President and Chief Executive Officer | ||
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Exhibit 99.1
OS Therapies Announces EMA Initiates Rolling Review of Conditional Marketing Authorization Application for OST-HER2 in the Prevention or Delay of Recurrence in Fully Resected Pulmonary Metastatic Osteosarcoma
Conference call scheduled for Thursday, April 30, 2026, at 8:30 am ET to review new OST-HER2 immune pharmacodynamic biomarker response (seroconversion) data and review regulatory successes validating the OST-HER2 approach. Participants will include strategic advisors Dr. Craig Eagle and Dr. Bob Langer, and Osteosarcoma key opinion leader Dr. Peter Anderson from Cleveland Clinic.
| ● | EMA and Australia TGA (ATGA) align on 3-year overall survival as the approvable clinical efficacy endpoint for Conditional Marketing Authorizations (CMAs), with alignment also achieved on confirmatory Phase 3 initiation, initially only in Australia, planned for Q3 2026 to meet regulatory requirement to support early approvals in the U.S., U.K., Europe and Australia |
| ● | Alignment achieved with EMA and ATGA on Seroconversion data serving as surrogate clinical efficacy data to support CMAs for early market access and eligibility for a Priority Review Voucher (PRV) under Rare Pediatric Disease Designation (RPDD) |
| ● | Alignment achieved with EMA and ATGA on non-clinical, CMC and safety data |
| ● | Alignment achieved with ATGA on existing drug product being used to initiate Phase 3 |
| ● | EMA selects Company into Raw Data Pilot Program |
| ● | OST-HER2 granted ATMP designation by U.K. MHRA |
| ● | Company forecasts European peak OST-HER2 osteosarcoma sales exceeding $300 million following ATMP designation grant, with over $50 million in sales expected in 2027 |
| ● | Upcoming U.S. FDA and U.K MHRA meetings scheduled in 2nd quarter of 2026 |
| ● | OST-504 Phase 1b castrate resistant prostate cancer trial biomarker analysis to mirror OST-HER2 Phase 2b osteosarcoma biomarker analysis |
| ● | OST-503 Phase 2 non-small cell lung cancer candidate indications expanded to include pancreatic cancer following review of target vector antigens include all KRAS G12 position mutations, which represents 76% of all KRAS mutations in cancer |
New York, NY, April 30, 2026 – OS Therapies, Inc. (NYSE American: OSTX) (“OS Therapies” or “the Company”), the world leader in gene-edited, listeria-based cancer immunotherapies, today announced that the European Medicines Agency (EMA)’s Committee for Advanced Therapy (CAT), in conjunction with the Committee for Medicinal Products for Human Use (CHMP) and Pharmacovigilance Risk Assessment Committee (PRAC), has initiated Continuous Evaluation (“Rolling Review”) of the OST-HER2 Conditional Marketing Authorisation (CMA) request regulatory dossier for the prevention of recurrence in fully resected, pulmonary metastatic osteosarcoma.1 The Company also announced that it was selected into EMA’s Raw Data Pilot programme that will done in concert with the EMA Scientific Advice Working Party (SAWP).
Australia Therapeutic Goods Association (ATGA) has also invited the OS Therapies to make an application for Provisional Determination, the Australian equivalent of a Conditional Marketing Authorisation of the OST-HER2 regulatory dossier, and is expected to make a decision on rolling review following the receipt of the Clinical Trial Notification (CTN) for the confirmatory Phase 3 trial later this quarter that will position the OS Therapies to initiate the confirmatory Phase 3 in the third quarter of 2026.
“I am delighted with the regulatory interactions OS Therapies has had to date, and I look forward to supporting OS Therapies in upcoming meetings with U.S. and U.K regulators,” said Dr. Craig Eagle, strategic advisor for OS Therapies.
OST-HER2 Immune Pharmacodynamic Biomarkers Conference Call Details
Title: OS Therapies (NYSE: OSTX) | Conference Call: OST-HER2 immune pharmacodynamic response biomarkers
Date: April 30th, 2026
Time: 8:30 AM Eastern Time
Registration Link: https://zoom.us/webinar/register/WN_Xlmj7kdNTH6C0MA_xdwiiQ
EMA OST-HER2 Rolling Review Status
OS Therapies and EMA have agreed that 3-year overall survival data will serve as the basis to complete evaluation of the CMA request. The Company’s recently submitted clinical efficacy data includes 2-year overall survival data, with EMA requesting updated 2.5-year overall survival data that will be available by the middle of the second quarter of 2026, and 3-year overall survival data that will become available early in the fourth quarter of 2026, which will complete the CMA submission. The Company anticipates a potential CMA decision by EMA in the fourth quarter of 2026. Market access interactions related to reimbursement with the UK’s NICE and EMA Health Technology Assessment (HTA) processes have commenced simultaneously to minimize the time between regulatory approval(s) and patient access to treatment. International regulatory coordination has also commenced under the EMA FDA Information Sharing programme2.
Additionally, the Company has been granted Advanced Therapy Medicinal Product designation from the U.K. Medicines and Healthcare products Regulatory Agency (MHRA)3 by virtue of its reciprocal designation agreement with EMA.
| 1 | https://www.ema.europa.eu/en/about-us/how-we-work/data-regulation-big-data-other-sources/use-clinical-study-data-medicine-evaluation |
| 2 | https://www.fda.gov/drugs/cder-international-program/international-agreements-information-sharing |
| 3 | https://www.gov.uk/guidance/advanced-therapy-medicinal-products-regulation-and-licensing |
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“We are grateful for EMA and ATGA’s strong support of our OST-HER2 program as we urgently work to improve outcomes for patients facing this rare and deadly pediatric cancer,” said Paul Romness, Chair and Chief Executive Officer of OS Therapies. “With all currently available data submitted and key regulatory alignment achieved, we are advancing toward early market access via Conditional Marketing Authorizations in Europe, the U.K., and Australia, as well as a U.S. Biologics License Application (BLA) under Accelerated Approval. Following our recent ATMP designation in Europe, we believe peak European sales could exceed $300 million annually, with the potential to generate more than $50 million in sales beginning in 2027.” Mr. Romness continued: “We have aligned with EMA and ATGA on the provisional design of our global confirmatory Phase 3 trial that is required to be initiated prior to being granted early market access, including 3-year overall survival as the primary efficacy endpoint. 3-year overall survival will also be the efficacy endpoint that will serve as the basis for potential early market access in the U.S., U.K., Europe, and Australia. This gives us strong confidence as we head into upcoming FDA and MHRA meetings, while reinforcing the growing recognition of our pharmacodynamic biomarker response seroconversion data as a meaningful surrogate for the key overall survival efficacy endpoint, further supporting our global regulatory pathway. We are delighted that immunotherapies are becoming more central in the approach to treating cancers globally, which bolsters OST-HER2 and the rest of our attenuated listeria monocytogenes platform candidates.”
“With the significant momentum we now have surrounding OST-HER2 in osteosarcoma, we are actively working to be prepared for the time when resources become available to advance our exciting listeria monocytogenes platform pipeline,” said Robert Petit, PhD, Chief Medical and Scientific Officer at OS Therapies. “Based upon the extensive biomarker work we have done to date on the OST-HER2 osteosarcoma program, we are now positioned to generate congruent data for the OST-504 castration-resistant prostate cancer program. Additionally, following significant advancement in the exciting KRAS-targeted antibody pancreatic cancer field with important clinical data showing significant survival benefit, we have identified that our promising Phase 2 non-small cell lung cancer (NSCLC) candidate OST-503 was constructed to target all KRAS G12 position-related antigen mutations, which represents 76% of all KRAS mutations in cancer. As a result, we believe OST-503 could represent a highly complementary approach to KRAS-target antibodies currently in development.”
OST-HER2 has received Orphan Drug Designation (ODD), Fast Track Designation (FTD) and Rare Pediatric Disease Designation (RPDD) from the FDA, and ODD, FTD and ATMP from the EMA. Under the RPDD program, if the Company receives a BLA in the United States, it will become eligible to receive a Priority Review Voucher (PRV) that it intends to sell. The Company is seeking to obtain a BLA under the Accelerated Approval Program for OST-HER2 in osteosarcoma in the second half of 2026, in addition to CMAs in Europe, the U.K. and Australia.
Upcoming 2nd Quarter Milestones
| ● | 2.5-year overall survival data |
| ● | FDA Pre-BLA Type B meeting to gain alignment on surrogate clinical efficacy endpoints based on most up-to-date Phase 2b clinical, biomarker and CMC, following the December 2025 alignment achieved non-clinical and safety data |
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| ● | Regenerative Medicine Advanced Therapy designation (“RMAT” – FDA equivalent to EMA ATMP designation) decision to be based upon preliminary evidence of efficacy supported by clinical and biomarker data metrics aligned upon |
| ● | FDA rolling review decision based upon pre-BLA meeting outcome |
| ● | FDA Type C meeting to gain alignment on the design of the confirmatory Phase 3 study |
| ● | Submission of the Accelerated Approval BLA request to FDA |
| ● | MHRA meeting to gain alignment on the design of the confirmatory Phase 3 study |
| ● | Submission of CMA request to MHRA |
| ● | MHRA rolling review decision based on Phase 3 confirmatory study design alignment |
| ● | Submission of CMA request to Australia in conjunction with Clinical Trial Notification (CTN) request for confirmatory Phase 3 study |
| ● | Receipt of approximately 1.45 million GBP in non-dilutive cash VAT tax refund |
About OS Therapies
OS Therapies is a clinical stage oncology company focused on the identification, development, and commercialization of treatments for Osteosarcoma (OS) and other solid tumors. The Company is the world leader in listeria-based cancer immunotherapies. OST-HER2, the Company’s lead asset, is an immunotherapy leveraging the immune-stimulatory effects of Listeria bacteria to initiate a strong immune response targeting the HER2 protein. OST-HER2 is designed to target two mutated extracellular epitopes and one mutated intracellular epitope of the HER2 oncogene, requiring only one of these three epitopes to be present in a tumor (or micro-metastasis) to trigger the desired immune response. OST-HER2 has received Orphan Drug Designation (ODD), Fast Track Designation (FTD) and Rare Pediatric Disease Designation (RPDD) from the U.S. Food & Drug Administration and has received ODD, FTD and ATMP from the European Medicines Agency.
The Company reported positive data in its Phase 2b clinical trial of OST-HER2 in recurrent, fully resected, lung metastatic osteosarcoma, demonstrating clinically significant benefit in the 12-month event free survival (EFS) primary endpoint of the study and the overall survival (OS) secondary endpoint. The Company anticipates receiving a Biologics License Application (BLA) from the U.S. FDA for OST-HER2 in osteosarcoma in 2026 and, if approved, would become eligible to receive a Priority Review Voucher that it could then sell. The Company also anticipates receiving Conditional Marketing Authorisations from the U.K.’s Medicines and Healthcare products Regulatory Agency and the EMA for OST-HER2 in 2026. OST-HER2 has completed a Phase 1 clinical study primarily in breast cancer patients, in addition to showing preclinical efficacy data in various models of breast cancer. OST-HER2 has been conditionally approved by the U.S. Department of Agriculture for the treatment of canines with osteosarcoma. The Company also anticipates reading out data from a Phase 1b study of OST-504 in castration resistant prostate cancer in the first half of 2026.
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In addition, OS Therapies is advancing its next-generation Antibody Drug Conjugate (ADC) and Drug Conjugates (DC), known as tunable ADC (tADC), which features tunable, tailored antibody-linker-payload candidates. This platform leverages the Company’s proprietary silicone Si-Linker and Conditionally Active Payload (CAP) technology, enabling the delivery of multiple payloads per linker. For more information, please visit www.ostherapies.com.
Forward-Looking Statements
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of the federal securities laws. These forward-looking statements and terms such as “anticipate,” “expect,” “intend,” “may,” “will,” “should” or other comparable terms involve risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. Those statements include statements regarding the intent, belief or current expectations of OS Therapies and members of its management, as well as the assumptions on which such statements are based. OS Therapies cautions readers that forward-looking statements are based on management’s expectations and assumptions as of the date of this press release and are subject to certain risks and uncertainties that could cause actual results to differ materially, including, but not limited to our expected to provide cash runway into 2027, the intended use of net proceeds from the offering, the potential approval of OST-HER2 by the U.S. FDA and other risks and uncertainties described in “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and other subsequent documents the Company files with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by the federal securities laws, OS Therapies specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.
OS Therapies Contact Information:
Investor Relations
Harrison Seidner, PhD
WaterSeid Partners
OSTX@waterseid.com
Public Relations
Stephanie Chen
Elev8 New Media
media@ostherapies.com
https://x.com/OSTherapies
https://www.instagram.com/ostherapies/
https://www.facebook.com/OSTherapies/
https://www.linkedin.com/company/os-therapies/
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Exhibit 99.2
NYSE American: OSTX Biomarker - focused Conference Call April 30, 2026
Safe Harbor Statement This document contains forward - looking statements . In addition, from time to time, we or our representatives may make forward - looking statements orally or in writing . We base these forward - looking statements on our expectations and projections about future events, which we derive from the information currently available to us . Such forward - looking statements relate to future events or our future performance, including : our financial performance and projections ; our growth in revenue and earnings ; and our business prospects and opportunities . You can identify forward - looking statements by those that are not historical in nature, particularly those that use terminology such as “may,” “should,” “expects,” “anticipates,” “contemplates,” “estimates,” “believes,” “plans,” “projected,” “predicts,” “potential,” or “hopes” or the negative of these or similar terms . In evaluating these forward - looking statements, you should consider various factors, including : our ability to change the direction of the Company ; our ability to keep pace with new technology and changing market needs ; and the competitive environment of our business . These and other factors may cause our actual results to differ materially from any forward - looking statement . Forward - looking statements are only predictions . The forward - looking events discussed in this document and other statements made from time to time by us or our representatives, may not occur, and actual events and results may differ materially and are subject to risks, uncertainties and assumptions about us . We are not obligated to publicly update or revise any forward - looking statement, whether as a result of uncertainties and assumptions, the forward - looking events discussed in this document and other statements made from time to time by us or our representatives might not occur .
Agenda 1. Introduction – Harrison Seidner, PhD 2. Corporate Update – Paul Romness, MPH 3. Biotech Innovation Curve – Dr. Robert Langer 4. Clinical, Biomarker and Safety Data – Andrew Exley, MD, FRCP, FRCPath 5. Regulatory status by Jurisdiction (Europe, Australia, U.K. and U.S.) – David Brindley, PhD 6. Insights on developing treatments for rare pediatric cancers – Dr. Craig Eagle 7. Questions
Agenda 1. Introduction – Harrison Seidner, PhD 2. Corporate Update – Paul Romness, MPH 3. Biotech Innovation Curve – Dr. Robert Langer 4. Clinical, Biomarker and Safety Data – Andrew Exley, MD, FRCP, FRCPath 5. Regulatory status by Jurisdiction (Europe, Australia, U.K. and U.S.) – David Brindley, PhD 6. Insights on developing treatments for rare pediatric cancers – Dr. Craig Eagle 7. Questions
Agenda 1. Introduction – Harrison Seidner, PhD 2. Corporate Update – Paul Romness, MPH 3. Biotech Innovation Curve – Dr. Robert Langer 4. Clinical, Biomarker and Safety Data – Andrew Exley, MD, FRCP, FRCPath 5. Regulatory status by Jurisdiction (Europe, Australia, U.K. and U.S.) – David Brindley, PhD 6. Insights on developing treatments for rare pediatric cancers – Dr. Craig Eagle 7. Questions
Agenda 1. Introduction – Harrison Seidner, PhD 2. Corporate Update – Paul Romness, MPH 3. Biotech Innovation Curve – Dr. Robert Langer 4. Clinical, Biomarker and Safety Data – Andrew Exley, MD, FRCP, FRCPath 5. Regulatory status by Jurisdiction (Europe, Australia, U.K. and U.S.) – David Brindley, PhD 6. Insights on developing treatments for rare pediatric cancers – Dr. Craig Eagle 7. Questions
• Major form of pediatric bone cancer • ~1,000 cases diagnosed annually in US • Primarily affects adolescents C young adults: 12 – 39 yrs • Localized disease • Chemotherapy C Surgery can sometimes achieve remission • Recurrent / Metastatic disease e.g. in Lungs • No FDA - approved treatment options for recurrent, resected lung metastases • Systematic reviews highlight dearth of new therapies (Gazouli 2021, Biermann 2025) • Some progress on disease mechanisms BUT • Prognosis is dire with little improvement over the last 30 years (Cole 2022) • Justifies use of historical control data Osteosarcoma: Clinical Outline
Age - Related Incidence of Primary s Subsequent Osteosarcoma Cole 2022
Overall Survival in Primary Osteosarcoma: No Improvement in 30 years Cole 2022
Overall Survival in Metastatic Osteosarcoma: No Improvement in 30 years Cole 2022
OST31 - 164: Innovation – Novel Immunotherapy 1. 1 st in class microbial vector gene therapy (MVGT) • Attenuated Listeria (Lm) bearing plasmids encoding chimeric fusion protein • Truncated Listerolysin: promotes Ag presentation C acts as adjuvant * • Tumour - associated antigen (TAA): Her2 2. Triggers a multi - modal anti - tumour immune response • Induces Her2 specific T cells • Boosts specific T cells to structurally unrelated TAAs * • Intratumoral Lm induces anti - tumour immunity as a cytosolic bacterium * • Boosts innate immune response to tumor – DCs, M1 monocytes, NK cells • Modulates tumour microenvironment – reduces MDSCs C Tregs
12 A Her2 Expression in BREAST & OVARIAN CANCER cytoplasm NUCLEUS Cell membrane HER2 receptor: Upregulated Nucleus What this means: HER2 is an “oncogenic driver” It actively causes the cancer to grow and spread. Upregulated: increased levels of Her2 expressed at cell surface Targetable by Antibodies (Ab): Ab - Drug conjugates (ADCs) or CAR - T cells Clinical Efficacy of ADCs: Trastuzumab - emtansine, Trastuzumab - duocarmycin VS Her2 Expression in OSTEOSARCOMA (BONE CANCER) cytoplasm Few Her2 molecules at cell surface NUCLEUS HER2 expressed in cell cytoplasm Processed into peptides, captured by MHC molecules, transported to cell surface as peptide - MHC complexes Nucleus What this means: Not an oncogenic driver: expression not mechanistically linked to cancer ~80% express HER2 but mostly cytoplasmic, low intensity, variable density Antibody - based detection (ADCs / CAR - T cells) limited by sensitivity Highly - sensitive T cells detect even low levels of HER2 - peptide - MHC complexes OST31 - 164: multi - modal action including T cells against Her2 and other TAAs How OST - HER2 works
How OST - HER2 works 13 3 4 1 L. monocytogenes ( Lm) A ttenuated HER2 - tLLO payload The Construct Attenuated Lm carrying plasmids encoding chimeric fusion protein - truncated listerolysin tLLO (a potent innate immune adjuvant) - HER2 sequences Administered by iv Infusion 2 DC Macro - phage Trojan Horse Entry Lm naturally targets professional antigen presenting cells = dendritic cells (DCs). Lm intracellular cytosolic pathogen generates anti - tumour immunity to multiple TAAs Antigen - presenting cells MHC I MHC II MHC I HER2 peptide Peptide - MHC Array DCs process & present TAA derived peptides as complexes with MHC I & MHC II receptors. Dual - pathway presentation primes CD8+ & CD4+ T cells Activates CD8+ and CD4+ CD8+ Killer T CD4+ Helper T NK NK cell Mono Monocyte DC Dendritic cell Treg MDSC Suppressors neutralised ظ Immune Activation CD8+ & CD4+ T cells primed against HER2 & other TAAs NK cells & M1 Monocytes activated Tumour immune - evasion mediators, Tregs & MDSCs, suppressed Multi - modal immune response: T cells + NK cells + Monocytes tLLO Adjuvant Effect Immune activation of HER2 specific & TAAs specific T cells i.e. broadens anti - tumour effect 5 CD8+ NK HER2 TUMOUR CELL Tumour Destruction NK cells target cancer stem cells Cytotoxic CD8+ T cells kill cancer cells CD4+ T cells promote memory Osteosarcoma cells in Micro Metastases eliminated
14 Gene transcript modulation as the preferred biomarker of response to OST - HER2 (OST31 - 164) ظ Why Not ELiSpot Alone? Canine trials: clinical benefit but no correlation with HER2 - specific T cells by ELiSpot Logistically challenging: requires viable blood samples from multiple centres and assays for multiple TAAs Misses the multi - modal (innate + adaptive) nature of the immune response to OST - HER2 ELISpot = T cell antigen - specific IFN - γ assay — sensitive but narrow in scope Reveals modulation across monocyte, NK, T cell, and Ag presentation pathways simultaneously . Multi - modal by design 1 Captures full response Routine sampling techniques sufficient Scalable across centres Transcript upregulation after 3 doses of OST31 - 164 correlates with outcomes in canine & human trials. Canine + human correlation 3 Evidenced 2 Operationally practical Why Gene Transcript Modulation? ض Biomarker strategy and trial findings
Her2 Expression by ImmunoHistoChemistry (CB11 murine mAb to intracellular domain AA 1244 – 1246) in Relapsed Osteosarcoma 15 Osteosarcoma Tumour Cells Her2 positive (Percent) EMA UPDATES – APRIL 2026 85% Her2 +ve Her2 - ve Reed 2025
OST31 - 164: Proof of Principle: Comparative Oncology 3. NIH supported collaboration with comparative oncology experts demonstrates efficacy of OST31 - 164 in spontaneous osteosarcoma in canines
Canine Osteosarcoma: Parallels with Human Osteosarcoma I. Spontaneous onset in immunocompetent dogs: rate >10x human rate II. Many clinical, biological, and molecular features in common i. Primary lesion: typically, high - grade tumours in long bones ii. Standard treatment: chemotherapy C radical surgery iii. Disease course: metastatic disease often in the lungs iv. Highly rearranged genomes often affecting TP53, CDKN2A, RB1 genes Similar molecular pathway alterations of prognostic significance • TH 1 C TH 2 immune cell signalling, Interferon signalling, Inflammatory responses III. IV. Share 3 distinct TME subtypes – independent predictors of PFS • Immune Enriched [IE]; IE dense extracellular matrix - like; Immune Desert Makielski 2019, Mannheimer 2023, Mason 2025, Patkar 2024
Immunological responses and clinical outcomes in dogs with osteosarcoma receiving SOC + ADXS31 - 164 Mason NJ 2025
Mason NJ 2025 # Up - regulation of Cytotoxic T cell, NK cell, & Ag presenting cell gene transcripts Canine Osteosarcoma Elite vs Short - term Survivors: PBMCs D ifferentially E xpressed G enes – Baseline vs last ADXS31 - 164 #
Primary Diagnosis Resection of Primary Tumor ~ Week 11 Cycle of OST31 - 164 - four treatments over 12 weeks Disease surveillance imaging every 12 weeks 6x Cycles of MAP Therapy over 29 weeks. ~10% Mortality ~50% recurrence after MAP Variable Time to Recurrence Lm Surveillance s Survival follow up for 3 yrs from last OST31 - 164 Relapse Diagnosis Resection of Metastasis & Screening Further cycles until Week 48 or Relapse or Withdrawal From Trial Variable interval to 1 st dose OST31 - 164 - 01: Clinical Trial in Recurrent (Pulmonary) Osteosarcoma
OST31 - 164: Innovation – Historic Controls 4. Justification for use of Historic Controls i. Lack of improvement in OS (Cole 2022) i. Reduces risk of bias thru improvements in Standard Of Care (SOC) ii. Systematic identification of published trials iii. Systematic screening for comparable populations iv. Conservative approach : treatment effect of chemotherapy +/ - IND in controls v. Systematic extraction of data from comparable populations
Rationale for EFS vs Objective Response Rate (ORR) I. Radiographic response may not reflect critical cellular effect II. Surgical resection is standard approach to pulmonary recurrence i.e. no lesion to determine ORR III. Likely difference in drug activity in microscopic vs macroscopic disease IV. Propose EFS vs historical benchmark A. Measurable, unresectable osteosarcoma • EFS < 4 months vs >4 months = disease control failure v success B. Completely resected osteosarcoma • EFS < 12 months vs >12 months Lagmay 2016
Rationale for Preferring Overall Survival to Event Free Survival in the Assessment of Immunotherapies for Osteosarcoma 1. Patients value Overall survival over Event Free Survival (Tregear 2024) 2. Regulators prefer Overall Survival as a Hard Endpoint 3. Delayed effect of immunotherapies reduces discriminating power of 12month Event Free Survival
Measures Reducing Potential Bias in Single Arm Trial of OST31 - 164 Measures Adopted to Reduce Potential bias Parameter Hard endpoints: Overall survival (OS) 1. Assessment bias Overall survival preferred to Event - Free Survival; Sensitivity analyses 2. Attrition bias Statistical analysis plan (SAP) pre - specified before data completion 3. Pre - planning Standard criteria for patient selection 4. Regression to mean Systematic selection of comparable control populations 5. Variability in Disease History Estimands defined in Statistical analysis plan 6. Intercurrent events Systematic selection of comparable control populations 7. Selection bias with controls Standard criteria for patient selection 8. Selection bias in study No improvement in Overall Survival in last 3 decades Controls include treatment effect of chemotherapy +/ - IND in controls 9. Trial bias due to improved SOC EMA/CHMP/458061/2024: Reflection paper on establishing efficacy based on single - arm trials
EFS vs OS after Immunotherapy: Single Arm Trial of Denosumab (RANKL mAb) in Patients with Recurrent / Refractory Osteosarcoma EFS OS Janeway 2026
OS: OST - HER2 Phase 2b Trial vs. Historical Control
OS: OST - HER2 Phase 2b Trial vs. Pooled Historical Control P=0.0344
Isolation of Treatment Effect • Clinically significant improvement in Overall Survival C EFS I. Highly significant link between Overall Survival C Immune Response Gene Signature (IRGS) after 3 rd dose of OST31 - 164 II. IRGS includes cytotoxic effectors (NK/T cells) C T cell memory, and modulators of Tumour MicroEnvironment (M1/M2, MDSCs) III. IRGS maps directly to the Mechanism of Action of OST31 - 164 IV. Clinical trial extends findings in parallel population of spontaneous osteosarcoma in canines: multi - modal immune response links Overall Survival to Mechanism of Action
Immune Response Gene Signatures after 3 rd Dose of OST31 - 164 Link Mechanism of Action to OS in Canine s Human Osteosarcoma • Cox Proportional Hazards Model • Canine IRGS (optimized): p=10e - 8 for Overall Survival • Beneficial: Ag presentation, NK cell activation, T cell activation • Detrimental: Type 1 IFN; M2 polarization; Myeloid Derived Suppressor Cells • Human IRGS (optimized): p=10e - 4 for Overall Survival • Beneficial: Ag presentation; NK cell activation; T cell activation/differentiation; M1 polarization • Detrimental: M2 polarization; failure to generate central memory CD8+ T cells
Kaplan Meier Analysis of Overall Survival by Immune Response Gene Composite (Baseline vs Post 3 rd Dose) Overall Survival Probability Days from 1st dose (Arrow ~ 2yrs)
Safety Profile III. I. Infusion related cytokine release syndrome • Frequency C severity reduced by pre - infusion regimen; no Rx discontinued • IV fluids, antihistamine, NSAID, antiemetic, H2 - receptor antagonist Cytokine release syndrome: maximum grade 2 intensity, 1 st cycle II. Infection risk • Single episode of asymptomatic bacteraemia in subject with indwelling infusion port; responsive to antibiotics C removal of port On - Target Off Tumor Effects • Her2 widely expressed at low level including skeletal C cardiac muscle • 1 episode of ?rhabdomyolysis: grade 3 ( haematuria + raised CK) in body builder • No signal in canine spontaneous osteosarcoma despite intensive monitoring
Agenda 1. Introduction – Harrison Seidner, PhD 2. Corporate Update – Paul Romness, MPH 3. Biotech Innovation Curve – Dr. Robert Langer 4. Clinical, Biomarker and Safety Data – Andrew Exley, MD, FRCP, FRCPath 5. Regulatory status by Jurisdiction (Europe, Australia, U.K. and U.S.) – David Brindley, PhD 6. Insights on developing treatments for rare pediatric cancers – Dr. Craig Eagle 7. Questions
Agenda 1. Introduction – Harrison Seidner, PhD 2. Corporate Update – Paul Romness, MPH 3. Biotech Innovation Curve – Dr. Robert Langer 4. Clinical, Biomarker and Safety Data – Andrew Exley, MD, FRCP, FRCPath 5. Regulatory status by Jurisdiction (Europe, Australia, U.K. and U.S.) – David Brindley, PhD 6. Insights on developing treatments for rare pediatric cancers – Dr. Craig Eagle 7. Questions
Agenda 1. Introduction – Harrison Seidner, PhD 2. Corporate Update – Paul Romness, MPH 3. Biotech Innovation Curve – Dr. Robert Langer 4. Clinical, Biomarker and Safety Data – Andrew Exley, MD, FRCP, FRCPath 5. Regulatory status by Jurisdiction (Europe, Australia, U.K. and U.S.) – David Brindley, PhD 6. Insights on developing treatments for rare pediatric cancers – Dr. Craig Eagle 7. Questions
Thank you for attending! OS Therapies, Inc. (NYSE American: OSTX)