Theriva's Virus Therapy for Pancreatic Cancer Gets EMA Go-Ahead

ROCKVILLE, MD – December 29, 2025 – Theriva™ Biologics has received a significant boost in its quest to combat one of the deadliest forms of cancer. The company announced today that it has received positive Scientific Advice from the European Medicines Agency (EMA) on the design of a crucial Phase 3 clinical trial for its lead drug candidate, VCN-01, aimed at treating metastatic pancreatic ductal adenocarcinoma (PDAC).

This feedback from the EMA’s Committee for Medicinal Products for Human Use (CHMP) marks a critical step forward, providing a clearer regulatory pathway in Europe for a potential new first-line treatment. The proposed trial will test VCN-01 in combination with the standard-of-care chemotherapy regimen, gemcitabine and nab-paclitaxel. For patients and clinicians grappling with the grim prognosis of metastatic pancreatic cancer, this development represents a tangible sign of progress in a field with a desperate need for new therapeutic options.

A European Regulatory Nod

The scientific advice from the EMA provides overall agreement with Theriva's proposed framework for the pivotal Phase 3 study. This is not a formal approval of the drug, but rather a strong endorsement of the clinical trial's design, which significantly de-risks the lengthy and costly process of late-stage drug development.

The CHMP advised that a single, well-conducted, randomized, and placebo-controlled Phase 3 trial could be sufficient to support a future marketing authorization application, provided the results demonstrate a compelling benefit-risk balance for patients. Key elements of the trial design that received the agency's backing include:

• Primary Endpoint: The trial will measure overall survival (OS) as its primary goal, the gold standard for oncology drug approval, which directly assesses whether a treatment helps patients live longer.
• Key Secondary Endpoints: The study will also track progression-free survival (PFS), duration of response, and patient-reported outcomes, providing a comprehensive picture of the drug's clinical benefit.
• Adaptive Design: The EMA agreed with the use of an adaptive trial design, a modern approach that allows for modifications to the trial based on interim data. This flexibility can help optimize the study's timeline and resources, potentially bringing a successful therapy to patients sooner.

“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 patients,” stated Steven A. Shallcross, Chief Executive Officer of Theriva Biologics, in a press release.

A Novel Dosing Strategy and a Unique Weapon

At the heart of the positive feedback is VCN-01 itself, an oncolytic adenovirus. This engineered virus is designed to be a dual-threat weapon against cancer. First, it selectively infects and replicates within tumor cells, causing them to burst and die—a process known as oncolysis. Second, and perhaps more critically for a notoriously difficult-to-treat cancer like PDAC, VCN-01 degrades the dense tumor stroma. This fibrous, protective barrier around tumors often prevents chemotherapy and the body's own immune cells from reaching their target. By breaking down this wall, VCN-01 can potentially enhance the effectiveness of co-administered treatments.

This mechanism was supported by results from the earlier VIRAGE Phase 2b trial, which showed that patients receiving VCN-01 with chemotherapy had improved survival outcomes compared to those on chemotherapy alone. Notably, the benefit was even greater in a subset of patients who received two doses of VCN-01.

Building on this finding, the EMA agreed with Theriva’s plan to administer repeated doses of VCN-01 in “macrocycles” throughout the treatment course. This allows for the possibility of giving patients three or more doses, a strategy the company hopes will yield even more significant survival benefits.

“We are particularly pleased with EMA agreement on the VCN-01 macrocycle dosing regimen,” Shallcross added. “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.”

Tackling a Formidable Foe

Pancreatic ductal adenocarcinoma accounts for over 90% of all pancreatic tumors and carries a devastatingly poor prognosis. The disease is often asymptomatic in its early stages, meaning the vast majority of patients are diagnosed only after the cancer has become locally advanced or has metastasized to other organs, such as the liver and lungs. At this point, surgical removal is typically not an option, and treatment focuses on extending life and managing symptoms.

It is estimated that 50-60% of patients already have distant metastases at the time of their diagnosis. This reality underscores the urgent need for more effective systemic therapies that can reach and destroy cancer cells throughout the body. VCN-01, which is administered intravenously, is designed to do just that, targeting both the primary tumor and its metastatic offshoots. The therapy has already received Orphan Drug and Fast Track designations in the United States, as well as Orphan Drug designation in Europe, highlighting its potential to address this high unmet medical need.

The Path Ahead

With a clear path forward in Europe, Theriva is now focused on aligning with U.S. regulators. The company plans to schedule an End-of-Phase 2 meeting with the Food and Drug Administration (FDA) in the first half of 2026. The goal is to finalize a single, multinational Phase 3 protocol that satisfies the requirements of both major regulatory bodies, streamlining the global development effort.

Regulatory clarity is also crucial for securing the partnerships necessary to fund large-scale pivotal trials and manufacturing scale-up. The company reported having $15.5 million in cash as of November 2025, providing a financial runway into the first quarter of 2027 to complete these regulatory activities and partnership discussions.

Beyond pancreatic cancer, Theriva is also planning to seek advice from both the EMA and FDA in 2026 for a potential trial of VCN-01 in retinoblastoma, a rare and challenging childhood eye cancer. This further demonstrates the potential breadth of the oncolytic virus platform, which has been studied in a range of cancers including head and neck, ovarian, and colorectal cancer. This regulatory momentum for its lead program could provide a significant tailwind for the company's broader ambitions.