On September 30, 2026 Theriva Biologics (NYSE American: TOVX), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, reported that detailed analysis of results from the VIRAGE Phase 2b clinical trial of VCN-01 (zabilugene almadenorepvec) in metastatic pancreatic cancer patients were published in Nature Medicine. The article, entitled "Intravenous hyaluronidase-expressing oncolytic adenovirus with chemotherapy in metastatic pancreatic cancer: a randomised phase 2b trial", can be read here.
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"We are proud to see the peer-reviewed results from the VIRAGE trial published in Nature Medicine and made available to the entire scientific community," said Manel Cascalló, PhD, General Director of Theriva Biologics S.L. and co-author of the article. "As elaborated in the publication, improved overall survival, progression free survival, and duration of response were observed in metastatic pancreatic cancer patients treated with VCN-01 combined with standard-of-care (SoC) gemcitabine/nab-paclitaxel chemotherapy compared to patients receiving SoC chemotherapy alone. Moreover, the Kaplan-Meier survival analysis and the timing of responses in VCN-01 treated patients suggest an immune mediated mechanism of action for VCN-01 in addition to its stroma degrading effects. We are excited about the potential for VCN-01 in different cancer therapy combinations, and we are extremely grateful to the patients who participated in VIRAGE, their families, our clinical investigators and their teams, and our co-authors for their commitment, dedication and diligence."
As previously reported, greater improvements in patient survival during the VIRAGE study were observed in metastatic pancreatic cancer patients receiving 2 doses of VCN-01 administered 3 months apart, Following End-of-Phase 2 feedback from both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), Theriva has recently initiated VIRAGE2; a small Phase 2a study designed to evaluate the feasibility of more frequent, repeated dosing of VCN-01 in combination with SoC chemotherapy. The first patient in VIRAGE2 was treated in August 2026, and the study is expected to complete enrollment during the second half of 2026. Initial pharmacodynamic and safety/tolerability data are anticipated by Q3 2027. Results from VIRAGE2 will inform the VCN-01 dosing regimen for potential evaluation in a future pivotal Phase 3 clinical trial. For more details see About VIRAGE2 below.
In parallel with VIRAGE2, Theriva is engaging with the FDA to finalize the design of a potential Phase 2/3 study evaluating VCN-01 in children with retinoblastoma with vitreous seeds that are refractory/resistant to the use of current intravitreal chemotherapy. VCN-01 has received Rare Pediatric Disease designation for the treatment of retinoblastoma and may be eligible to receive a Priority Review Voucher if VCN-01 is approved in this indication by September 30, 2029.
About Pancreatic Ductal Adenocarcinoma
Cancer of the pancreas consists of two main histological types: cancer that arises from the ductal (exocrine) cells of the pancreas or, much less often, cancers may arise from the endocrine compartment of the pancreas. Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of all pancreatic tumors. It can be located either in the head of the pancreas or in the body/tail. Pancreatic cancer usually metastasizes to the liver and peritoneum. Other less common metastatic sites are the lungs, brain, kidney, and bone. In its early stages, pancreatic cancer does not typically result in any characteristic symptoms. In many instances, progressive abdominal pain is the first symptom. Therefore, in most cases, pancreatic cancer is diagnosed in its late stages (locally advanced non-metastatic or metastatic stage of the disease) when surgical resection and possibly curative treatment is not possible. It is generally assumed that only 10% of cases are resectable at presentation, whereas 30-40% of patients are diagnosed at local advanced/unresectable stage and 50-60% present with distant metastases.
About VCN-01
VCN-01 (zabilugene almadenorepvec) is a systemically administered oncolytic adenovirus designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma that serves as a significant physical and immunosuppressive barrier to cancer treatment. This unique mode-of-action is intended to enable VCN-01 to exert multiple antitumor effects by (i) selectively infecting and lysing tumor cells; (ii) enhancing the access and perfusion of co-administered chemotherapy products; and (iii) increasing tumor immunogenicity and exposing the tumor to the patient’s immune system and co-administered immunotherapy products. Systemic administration enables VCN-01 to exert its actions on both the primary tumor and metastases. VCN-01 has been administered to 142 patients to date in Company- and investigator-sponsored clinical trials in different cancers, including PDAC (in combination with chemotherapy), head and neck squamous cell carcinoma (with an immune checkpoint inhibitor), ovarian cancer (with CAR-T cell therapy), colorectal cancer, and retinoblastoma (by intravitreal injection). VCN-01 has also been made available for compassionate use in retinoblastoma patients, and 2 patients have been treated in this program. VCN-01 has been granted Orphan Drug designation for the treatment of metastatic PDAC and retinoblastoma in Europe and the USA, as well as FDA Fast Track designation for the treatment of metastatic PDAC and Rare Pediatric Disease designation for the treatment of retinoblastoma. More information on VCN-01 clinical trials is available at Clinicaltrials.gov.
About VIRAGE
VIRAGE (EUCT 2024-511290-30-00; NCT05673811) was a two-arm, Phase 2b open-label, randomized, controlled, multicenter clinical trial in patients with histologically confirmed, newly-diagnosed metastatic PDAC. A total of 112 patients were enrolled at 5 sites in the U.S. and 9 sites in Spain. In both the control and VCN-01 (zabilugene almadenorepvec) treatment arms, patients received gemcitabine/nab-paclitaxel standard-of-care (SoC) chemotherapy in repeated 28-day cycles until disease progression. In the VCN-01 treatment arm only, patients were also administered intravenous VCN-01 seven-days prior to starting the first and fourth cycles of gemcitabine/nab-paclitaxel treatment (study days 1 and ~92 respectively). As previously reported and presented, PDAC patients in the VCN-01 plus gemcitabine/nab-paclitaxel SoC treatment arm demonstrated increased overall survival, progression free survival, and duration of response compared to patients in the control arm treated with gemcitabine/nab-paclitaxel SoC alone. Greater improvements in these parameters were observed in patients who received 2 doses of VCN-01 administered 3 months apart, and the pharmacokinetics of VCN-01 were not different between the 2 doses despite the presence of neutralizing antibodies.
About VIRAGE2
VIRAGE2 (EUCT: 2026-525566-21-00; NCT07701486) is a Phase 2a, single-arm, open-label, clinical trial in 6 evaluable patients with histologically confirmed, newly diagnosed metastatic PDAC enrolled at a single site in Spain. Patients are intended to receive at least three "macrocycles" of VCN-01 (zabilugene almadenorepvec) and gemcitabine/nab-paclitaxel SoC chemotherapy, followed by SoC gemcitabine/nab-paclitaxel cycles until disease progression. In each VCN-01 macrocycle, intravenous VCN-01 is administered on day 1 followed by gemcitabine/nab-paclitaxel SoC chemotherapy on days 8, 15, 22, 36, 43, and 50. Macrocycles are repeated on days 57 and 113. The primary objective of the VIRAGE2 trial is to evaluate whether administration of at least 3 doses of VCN-01, with 2 months between doses, is well tolerated by patients without adversely impacting VCN-01 pharmacodynamics. Primary endpoints for the trial are the adverse event profile and levels of VCN-01 viral genomes in blood. Secondary endpoints include objective response rate, duration of response, progression free survival, overall survival, and circulating levels of anti-VCN-01 neutralizing antibodies. Exploratory endpoints include estimates of potential VCN-01 shedding by measuring VCN-01 viral genomes in sputum and stool. The study is not formally powered for evaluation of clinical efficacy endpoints and is intended to support evaluation of the potential efficacy of the more frequent repeated dosing regimen in subsequent clinical trials.
(Press release, Theriva Biologics, SEP 30, 2026, View Source [SID1234671187])