Theriva Biologics Receives EMA Scientific Advice for VCN-01 Phase 3 Trial in Metastatic Pancreatic Cancer
Key Insights
The European Medicines Agency (search) provided scientific advice supporting Theriva Biologics' proposed Phase 3 trial design for VCN-01 combined with standard chemotherapy in metastatic pancreatic ductal adenocarcinoma (search).
EMA agreed with key trial parameters including sample size, adaptive design, and repeated dosing regimen based on improved survival outcomes observed in patients receiving multiple VCN-01 doses.
Theriva plans to meet with FDA in the first half of 2026 to finalize the pivotal multinational Phase 3 trial protocol, with cash runway extending to Q1 2027.
Theriva Biologics announced receipt of positive Scientific Advice from the European Medicines Agency (search)'s Committee for Medicinal Products for Human Use (CHMP) regarding the design of a Phase 3 clinical trial for VCN-01 in combination with gemcitabine/nab-paclitaxel for first-line treatment of metastatic pancreatic ductal adenocarcinoma (search) (PDAC (search)). The regulatory guidance represents a significant milestone for the oncolytic adenovirus therapy, which has demonstrated promising survival benefits in earlier-stage trials.
EMA Endorses Comprehensive Trial Design
The CHMP provided overall agreement with Theriva's proposed Phase 3 clinical trial design, including critical parameters such as sample size, repeated dosing of VCN-01, and an adaptive design to potentially optimize trial timelines and outcomes. The agency advised that a potential future marketing authorization application for VCN-01 in metastatic PDAC (search) could be supported by a single, high-quality, double-blinded, randomized, placebo-controlled Phase 3 trial demonstrating a compelling benefit-risk ratio.
The scientific advice encompassed agreement on proposed inclusion/exclusion criteria, primary endpoint of overall survival, and secondary endpoints including progression-free survival, duration of response, and patient-reported outcomes. Importantly, CHMP recognized the increased improvement in overall survival observed in patients receiving two doses of VCN-01 in the VIRAGE study and agreed with the proposed dosing regimen using repeated "macrocycles" that would enable administration of more than two doses in the Phase 3 trial.
Building on Promising Phase 2b Results
The regulatory guidance builds upon results from the VIRAGE randomized, controlled Phase 2b clinical trial, which demonstrated that PDAC (search) patients treated with VCN-01 plus gemcitabine/nab-paclitaxel standard-of-care showed increased overall survival, progression-free survival, and duration of response compared to patients receiving standard chemotherapy alone. Even greater improvements in these parameters were observed in patients who received two doses of VCN-01 administered three months apart.
"We are very encouraged by the scientific advice we received from the EMA regarding our proposed pivotal Phase 3 trial of VCN-01 plus gemcitabine/nab-paclitaxel SoC in metastatic PDAC (search) patients," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "We are particularly pleased with EMA agreement on the VCN-01 macrocycle dosing regimen. As we demonstrated in the VIRAGE Phase 2b study, patients who received 2 doses of VCN-01 had improved survival outcomes, therefore we anticipate 3 or more doses of VCN-01 should provide an even greater survival benefit."
Regulatory Path Forward
Theriva plans to schedule an End-of-Phase 2 meeting with the FDA in the first half of 2026 to finalize the design of the pivotal multinational Phase 3 clinical trial. The company aims to deliver an innovative therapeutic option for patients diagnosed with this rapidly fatal disease. VCN-01 has been granted Orphan Drug designation for the treatment of metastatic PDAC (search) in both Europe and the USA, as well as Fast Track designation in the USA.
Beyond the PDAC (search) program, interactions with EMA and FDA are planned for 2026 to seek advice on a potential Phase 2/3 trial for VCN-01 in retinoblastoma (search), a challenging childhood cancer for which VCN-01 has been granted Rare Pediatric Disease designation.
Unique Mechanism of Action
VCN-01 is a systemically administered oncolytic adenovirus designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma (search) that serves as a significant physical and immunosuppressive barrier to cancer treatment. This unique mode of action enables VCN-01 to exert multiple antitumor effects by selectively infecting and lysing tumor cells, enhancing access and perfusion of co-administered chemotherapy products, and increasing tumor immunogenicity while exposing the tumor to the patient's immune system.
The therapy has been administered to 142 patients to date in company- and investigator-sponsored clinical trials across different cancers, including PDAC (search) in combination with chemotherapy, head and neck squamous cell carcinoma (search) with immune checkpoint inhibitors, ovarian cancer (search) with CAR-T cell therapy, colorectal cancer (search), and retinoblastoma (search) by intravitreal injection.
Financial Position and Strategic Outlook
As of November 10, 2025, Theriva reported $15.5 million in cash and equivalents, providing runway into Q1 2027 as the company completes interactions with regulatory agencies regarding the PDAC (search) and retinoblastoma (search) programs and pursues partnerships to support VCN-01 manufacturing scale-up and conduct of the proposed pivotal clinical trials.
Shallcross emphasized that regulatory clarity on development pathways is essential for ongoing partnering efforts for VCN-01 clinical programs, positioning the company to advance this potentially transformative therapy for patients with limited treatment options in pancreatic cancer (search) and other solid tumors.