Theriva Biologics Announces Promising Results from VCN-01 Phase 1 Clinical Trial in Head and Neck Cancer

Key Highlights

• Prolonged Overall Survival (OS): Significant extension of overall survival was observed in heavily pre-treated, refractory Head & Neck Squamous Cell Carcinoma (HNSCC) patients when administered VCN-01 intravenously prior to the immune checkpoint inhibitor durvalumab.
• Mechanism of Action Confirmed: Pharmacokinetic, tissue biopsy, radiomic, and transcriptomic data support VCN-01’s ability to degrade tumor stroma, enhance immune responses, and resensitize refractory tumors to immunotherapy.
• Publication in a Leading Journal: Results from the Phase 1 trial were published online in the prestigious journal Clinical Cancer Research, further validating the clinical and scientific significance of the findings.
• Biomarker Evidence: Increased levels of PD-L1 positive T-cells and other biomarkers were observed post-treatment, indicating reactivation of the immune system.

Detailed Results from Phase 1 Clinical Trial

• Study Design: The trial enrolled 20 adult patients with metastatic or refractory HNSCC whose disease had progressed despite prior therapies, including anti-PD-(L)1 inhibitors.
• Study Arms:
  • Arm I LD (Concomitant): 6 patients received low dose (3.3E12 virus particles) IV VCN-01 4 hours before a fixed dose of durvalumab (1500 mg every 4 weeks).
  • Arm II LD (Sequential, Low Dose): 8 patients received low dose IV VCN-01 14 days prior to IV durvalumab.
  • Arm II HD (Sequential, High Dose): 6 patients received high dose (1.0E13 virus particles) IV VCN-01 14 days before IV durvalumab.
• Clinical Outcomes:
  • Median Progression-Free Survival (PFS):
    Arm I LD: 1.6 months
    Arm II LD: 3.7 months
    Arm II HD: 2.1 months
  • Median Overall Survival (OS):
    Arm I LD: 10.3 months
    Arm II LD: 15.5 months
    Arm II HD: 17.3 months
• Mechanistic and Biomarker Insights:
  • Significant increases in circulating PH20, a stroma-degrading enzyme expressed during VCN-01 replication, were observed in all tested patients, peaking between days 3-8 and remaining detectable up to day 28 in most cases.
  • VCN-01 viral genome levels in blood also showed two peaks, indicating ongoing viral replication and return to circulation.
  • Biopsy analysis showed upregulation of CD8 and IDO, suggesting increased infiltration by activated cytotoxic T cells—a marker historically associated with improved survival in HNSCC.
  • Reductions in FoxP3, CD25, and CTLA4 were recorded, implying a decrease in tumor regulatory T cells and tumor immunosuppression.
  • Upregulation of PD-1 and PD-L1 in most patients after VCN-01 administration correlated with survival, suggesting enhanced immune activity and increased effectiveness of subsequent durvalumab treatment.

Corporate and Platform Updates

• Theriva Biologics, Inc. is a diversified, clinical-stage company developing novel therapeutics for cancer and related diseases with high unmet need. Its lead candidate, VCN-01 (zabilugene almadenorepvec), is an oncolytic adenovirus platform designed for IV, intravitreal, and antitumoral delivery, aiming to trigger tumor cell death, enhance the efficacy of co-administered therapies, and stimulate a robust anti-tumor immune response.
• An exploratory trial with SYN-004 (ribaxamase), targeting prevention of microbiome damage in allogeneic hematopoietic cell transplant (HCT) recipients, has completed two of three cohorts. Initiation of the third cohort is pending additional funding.

Potential Price-Sensitive Information for Shareholders

• Clinical Validation: Positive Phase 1 results, including significant OS improvement in a difficult-to-treat patient population, and publication in a leading peer-reviewed journal, could increase investor confidence and potentially drive share price appreciation.
• Pipeline Progress: The success of VCN-01 in resensitizing tumors to immunotherapy and enabling further clinical development, particularly in combination with immune checkpoint inhibitors, positions the company as a potential leader in the oncolytic virus and immuno-oncology space.
• Funding and Partnerships: The company highlights the need for additional funding and/or partnerships to progress clinical trials, especially for SYN-004. The success or failure to secure such funding could significantly impact future development and shareholder value.
• Regulatory and Market Risks: Progression of VCN-01 toward regulatory approval and commercial viability remains subject to further clinical validation, regulatory review, ongoing financing, and market acceptance, which represent both opportunities and risks for investors.

Forward-Looking Considerations

Theriva Biologics cautions that statements regarding further clinical development, potential market adoption, regulatory approval, and financial projections are forward-looking and subject to various risks, including clinical trial outcomes, capital availability, regulatory hurdles, and competitive developments.

Contact Information

Investor Relations:
Kevin Gardner
LifeSci Advisors, LLC
[email protected]

Disclaimer: This article is for informational purposes only and does not constitute investment advice. Investors should conduct their own due diligence and consult with their financial advisors before making investment decisions. All forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those anticipated.

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