- Patients treated with VCN-01 (zabilugene almadenorepvec) plus standard gemcitabine/nab-paclitaxel chemotherapy had increased overall survival, progression-free survival, and duration of response compared with patients treated with standard gemcitabine/nab-paclitaxel -

- VCN-01 was well tolerated, with transient and reversible adverse events (AEs), and met the primary safety endpoint -

- Greater differences between treatment arms were observed in patients who received two doses of VCN-01 -

Theriva™ Biologics, Inc. , a diversified clinical-stage company developing designed therapies to treat cancer and related diseases in areas of high unmet need, today announced positive preliminary results from VIRAGE, a Phase 2b clinical trial evaluating the Company’s lead product candidate VCN-01 (zabilugene almadenorepvec) in combination with standard chemotherapy (gemcitabine/nab-paclitaxel) as first-line therapy for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) for whom gemcitabine/nab-paclitaxel is the recommended first-line treatment option. VCN-01 is a systemically administered oncolytic adenovirus designed to target specific tumors and disrupt the stroma. The U.S. Food and Drug Administration (FDA) has granted it Orphan Drug Designation and Fast Track status for the treatment of pancreatic cancer.

The VIRAGE trial analysis (see “About VIRAGE” below) includes first-line treatment data from 96 patients with newly diagnosed metastatic PDAC:

• In the primary endpoint analysis, the 48 patients treated with at least one dose of standard gemcitabine/nab-paclitaxel had a median overall survival (OS) of 8.6 months, while the 48 patients treated with VCN-01 followed by at least one dose of standard gemcitabine/nab-paclitaxel had a median OS of 10.8 months (hazard ratio [HR] = 0.57; 95% confidence interval [CI]: 0.34-0.96; p = 0.0546).
• Improvements in OS in the VCN-01 plus standard therapy arm compared with the standard therapy control arm were reflected in an increase in progression-free survival (PFS) [median PFS 7.0 vs. 4.6 months; HR = 0.55; 95% CI 0.34-0.88; p = 0.0105].
• The median duration of response (DR) was 5.4 months (n = 15) in the standard-of-care control arm, whereas the median DR in the VCN-01 plus standard-of-care arm doubled to 11.2 months (n = 19; RR = 0.22; 95% CI: 0.08-0.62; p = 0.0035).

The increase in overall survival was greater in patients who received two doses of VCN-01 and four or more cycles of standard gemcitabine/nab-paclitaxel (n = 34) compared with patients who received four or more cycles of standard gemcitabine/nab-paclitaxel (n = 29) [median OS, 14.8 and 11.6 months, respectively; HR = 0.44, 95% CI: 0.21-0.92; p = 0.046], suggesting that the second dose of VCN-01 (given three months after the first dose) provides a significant additional benefit in this treatment subgroup.

“The encouraging preliminary data from the Phase 2b VIRAGE trial demonstrate the potential for VCN-01 to benefit patients with metastatic PDAC treated with standard gemcitabine/nab-paclitaxel chemotherapy,” said Steven A. Shallcross, CEO of Theriva Biologics. “The significant reduction in hazard ratios for survival parameters in the VCN-01 treatment group provides compelling evidence that VCN-01 in combination with gemcitabine/nab-paclitaxel can prolong the lives of patients with metastatic PDAC. These data, along with recent recommendations from the U.S. FDA and the European Medicines Agency (EMA), are expected to facilitate collaboration with industry partners and design a confirmatory Phase 3 trial that, if successful, could provide an important new therapeutic option for patients suffering from this rapidly fatal disease.”

As previously reported , the adverse event (AE) profile of VCN-01 was consistent with that observed in previous clinical trials. The most common AEs associated with VCN-01 (pyrexia, flu-like illness, vomiting, nausea, and elevated transaminases) were transient and reversible. These AEs were observed to be less frequent and of lower CTCAE grade after the second dose of VCN-01 (administered on approximately day 92) compared with the first dose of VCN-01 (administered on day 1). A review by an independent data monitoring committee noted that the overall type and number of AEs in the VCN-01 treatment group were as expected for the pancreatic cancer population, the duration of treatment, and the use of an oncolytic virus.