On August 6, 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 the dosing of the first patient in the VIRAGE2 Phase 2a clinical trial, a small proof-of-concept study evaluating more frequent repeated dosing of VCN-01 (zabilugene almadenorepvec) in first-line metastatic PDAC patients treated with standard-of-care gemcitabine/nab-paclitaxel chemotherapy (SoC; see About VIRAGE2 below). Enrollment into the VIRAGE2 trial is expected to be completed in H2 2026 and initial pharmacodynamic and safety/tolerability data are anticipated by Q3 2027. Results from this trial will inform the VCN-01 dosing regimen for potential evaluation in a future pivotal Phase 3 clinical trial.

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The VIRAGE2 clinical trial is based on observations from the VIRAGE Phase 2b clinical trial in metastatic PDAC patients where patients administered 2 doses of VCN-01 in combination with gemcitabine/nab-paclitaxel SoC chemotherapy exhibited improved overall survival, progression-free survival, and duration of response compared to patients treated with SoC chemotherapy alone. As previously reported, both EMA scientific advice and FDA meeting feedback recognized the improved survival in the group treated with 2 doses of VCN-01, and raised the possibility of more frequent, repeated dosing of VCN-01 in combination with SoC chemotherapy to potentially improve clinical outcomes.

"The first patient dosed in VIRAGE2 marks an important clinical development milestone as the evaluation of more frequent, repeated dosing is a critical step in the advancement of VCN-01 towards a potential pivotal Phase 3 clinical trial in metastatic PDAC patients," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "Our current clinical data indicate that repeated administration of VCN-01 to metastatic PDAC patients may significantly increase its tumor stroma-degrading effects and further enhance the antitumor immune response. A positive outcome from the VIRAGE2 trial will enable us to refine the design and dosing regimen of our proposed pivotal Phase 3 clinical trial in metastatic PDAC patients treated with SoC chemotherapy. Since the tumor stroma is a challenge for multiple classes of cancer therapies, a repeated VCN-01 dosing regimen may also improve outcomes when combined with other interventions such as immunotherapies, antibody-drug conjugates, KRAS inhibitors, and emerging targeted cancer treatments."

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 VIRAGE2

VIRAGE2 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 standard-of-care (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 approximately 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 designed with 80% power to detect a difference in VCN-01 viral genome levels between the second and first VCN-01 doses with a 2-sided alpha of 0.05. 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 (EUCT: 2026-525566-21-00; NCT07701486).

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 enables 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. With the first patient dosed in VIRAGE2, VCN-01 has been administered to 143 patients 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. More information on VCN-01 clinical trials is available at Clinicaltrials.gov.

(Press release, Theriva Biologics, AUG 6, 2026, View Source [SID1234669849])