MHRA to Lead Global Review of OS Therapies' OST-HER2 in Metastatic Osteosarcoma Under Project Orbis
核心洞察
OS Therapies said the UK MHRA will take the lead regulatory role for OST-HER2 in fully resected, pulmonary metastatic osteosarcoma (搜索) under the FDA's Project Orbis framework.
The company reported FDA alignment on an amended adaptive Phase 3 design at a Type C Statistical Methods Meeting, with the UK portion set to start in mid-Q4 2026.
MHRA granted access to the UK Clinical Practice Research Datalink national patient registry to strengthen comparator data for the OST-400 natural history study.
OS Therapies said the UK Medicines and Healthcare products Regulatory Agency (MHRA) has agreed to become the lead regulatory agency driving early market access for OST-HER2 in the prevention or delay of recurrence in fully resected, pulmonary metastatic osteosarcoma (搜索), under the FDA's Project Orbis initiative. The company accepted MHRA's request to take that role, a step it says is intended to de-risk a harmonized global early market access pathway.
Project Orbis is the FDA Oncology Center of Excellence initiative launched in May 2019 to provide a framework for concurrent submission and review of oncology products among international partners. Since 2021, 29 MHRA-led oncology products have been approved by the FDA under the program.
FDA alignment on adaptive Phase 3 design
The company reported that a Type C Statistical Methods Meeting with the FDA produced alignment on an amended adaptive design for the pending Phase 3 study. That alignment allows the UK portion of the global study to begin using requalified material originally used in the Phase 2b study. OS Therapies expects the confirmatory Phase 3 trial to initiate in the UK in mid-Q4 2026, following requalification of the Phase 2b drug product.
FDA and the European Medicines Agency (搜索) have indicated they will allow the Phase 3 study to move forward in their jurisdictions once Phase 3-ready drug product is available. That same material is expected to support early market access commercial launch in the UK, US, Europe and Australia, in addition to other Project Orbis countries. OS Therapies said it expects to have Phase 3 and commercial-ready drug product in 2027 to support expansion of the trial into the US and Europe and to support commercial launch.
"With FDA aligning on the updated adaptive design of pending Phase 3 study in our recent Type C Statistical Methods Meeting, MHRA is now taking the lead in the international OST-HER2 regulatory review process under Project Orbis to de-risk our harmonized global regulatory early market access pathway," said Paul Romness, MPH, Chairman and CEO of OS Therapies.
UK registry data to sharpen comparator analysis
MHRA has granted the company access to the UK Clinical Practice Research Datalink, the UK national patient registry, to strengthen comparator data while the Phase 3 trial is ongoing. Some UK data are already included in the company's actively accruing OST-400 natural history study of osteosarcoma (搜索) patients, which was run concurrently with the OST-HER2 Phase 2b study timeline. MHRA has had access to the UK database as part of its review of the OST-HER2 regulatory dossier.
"With the confirmatory Phase 3 study set to initiate in the U.K. following requalification of material used as part of the Phase 2b study, access to the UK Database will further increase resolution of the magnitude of OST-HER2 treatment effect during the global early market access phase," Romness said.
Regulatory submissions and designations
OS Therapies is seeking a Conditional Marketing Authorisation Application from MHRA in the UK under Project Orbis for OST-HER2 in metastatic osteosarcoma (搜索) in the fourth quarter of 2026. The company said it has confirmation that MHRA will accept the pending CMAA submission, expected in the coming weeks. Immediately after the UK filing, the company plans to seek a Biologics License Application under the Accelerated Approval Program in the US, followed by CMAAs in Europe and Australia. The company continues to engage with the FDA on the non-Orbis Accelerated Approval route, and its BLA filing was initiated in Q1 2026 with completion pending in Q4 2026.
OST-HER2 holds Orphan Drug Designation, Fast Track Designation and Rare Pediatric Disease Designation from the FDA, and ODD, FTD and Advanced Therapy Medicinal Products status from the EMA. It holds ODD and ATMP status from MHRA, which also recruited the company into Project Orbis. OS Therapies has completed resubmission of a Regenerative Medicine Advanced Therapy request, and its Commissioner's National Priority Review Voucher letter of intent has been accepted by the FDA. The company is awaiting FDA decisions on RMAT, Rolling Review and CNPV.
Under the Rare Pediatric Disease Designation program, a US BLA grant would make the company eligible to receive a Priority Review Voucher that it intends to sell. A recent PRV sale occurred in August 2026 for $220 million, though the company stated there can be no assurance it would realize a comparable value in any future sale. BLAs granted via Project Orbis are eligible to receive PRVs and may also be granted through the Accelerated Approval Program.
Phase 2b results and pipeline
OS Therapies reported positive data from its Phase 2b clinical trial of OST-HER2 in the prevention or delay of recurrence in fully resected, pulmonary metastatic osteosarcoma (搜索), with clinically significant benefit on the 12-month event free survival primary endpoint and on the overall survival secondary endpoint. The company also disclosed that a patient previously reported as lost to follow-up has been confirmed to be alive.
OST-HER2 is an immunotherapy that leverages the immune-stimulatory effects of Listeria bacteria to initiate an immune response targeting the HER2 (搜索) protein. It is designed to target two mutated extracellular epitopes and one mutated intracellular epitope of the HER2 oncogene, requiring only one of the three epitopes to be present in a tumor or micro-metastasis to trigger the desired immune response. The agent completed a Phase 1 study primarily in breast cancer (搜索) patients and has shown preclinical efficacy in various breast cancer models. It was previously conditionally approved by the US Department of Agriculture for the treatment of canines with osteosarcoma (搜索).
Beyond OST-HER2, the company has completed dosing in a Phase 1 study of OST-504 (搜索) for castration-resistant prostate cancer (搜索). It is also advancing a next-generation antibody drug conjugate and drug conjugate platform known as tunable ADC, which features tunable antibody-linker-payload candidates and leverages the company's proprietary silicon Si-Linker and Conditionally Active Payload technology, enabling delivery of multiple payloads per linker.