Theriva Biologics, Inc. (TOVX) is a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need. The company's strategic focus has transitioned to oncology through the development of its oncolytic adenovirus platform, led by the promising candidate VCN-01.
Business Overview
In 2023, Theriva Biologics continued to make steady progress in advancing its oncology-focused portfolio. The company's primary efforts and resources have been dedicated to pursuing multiple therapeutic opportunities for its lead clinical candidate, VCN-01. VCN-01 is a systemically administered oncolytic adenovirus designed to selectively replicate within the tumor, degrade the tumor matrix, and increase tumor immunogenicity, positioning it for potential combination with chemotherapy and immuno-oncology products.
VCN-01 Clinical Progress
VCN-01 has been administered to more than 100 patients across diverse indications, including pancreatic ductal adenocarcinoma (PDAC), retinoblastoma, head and neck squamous cell carcinoma, colorectal cancer, and ovarian cancer. The company's most advanced program for VCN-01 is in PDAC, an indication with one of the lowest survival rates among all cancers. Theriva Biologics is currently conducting the VIRAGE Phase 2b trial, evaluating VCN-01 in combination with standard-of-care chemotherapy (gemcitabine and nab-paclitaxel) as a first-line therapy for patients with metastatic PDAC.
The VIRAGE trial remains on track to complete enrollment in the first half of 2024. In the first quarter of 2024, the company reported that the Independent Data Monitoring Committee (IDMC) recommended the continuation of enrollment as planned, with no safety concerns raised. Importantly, intravenous VCN-01 has been well-tolerated and demonstrated a safety profile consistent with prior clinical trials, with no additional toxicities observed in patients receiving a second dose of VCN-01, providing the first clinical evidence of the feasibility of repeated systemic dosing.
In addition to the VIRAGE trial, Theriva Biologics continues to work closely with key opinion leaders and regulatory agencies to refine its clinical strategy for VCN-01 in retinoblastoma. The company believes intravitreal VCN-01 has the potential to treat vitreous seeds in children with this devastating cancer. An investigator-sponsored Phase 1 trial evaluating the safety and activity of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma is on track to complete patient follow-up in the first half of 2024.
Pipeline and Technology
Beyond VCN-01, Theriva Biologics is pursuing new oncolytic virus candidates to leverage its novel Albumin Shield Technology, which is designed to protect systemically administered oncolytic viruses from the host immune system and may facilitate more frequent repeated administration of oncolytic virus therapies. This technology could enable the company's pipeline of products to be used in standardized treatment cycles that are well-established in cancer chemotherapy and immunotherapy.
Theriva Biologics' oncology-focused pipeline is further complemented by its ongoing Phase 1b/2a clinical trial of SYN-004 (ribaxamase) at Washington University. This trial is designed to evaluate the therapeutic potential of SYN-004 to reduce fatal adverse events related to IV beta-lactam antibiotic use in allogeneic hematopoietic cell transplant (HCT) recipients, including acute graft-versus-host-disease (aGVHD) and overgrowth and infection by pathological organisms such as C-difficile and vancomycin resistant Enterococci.
Financials
For the full year ended December 31, 2023, Theriva Biologics reported a net loss of 18.3 million and no revenue. The company's operating cash flow was negative 19.0 million, and its free cash flow was negative 19.2 million. As of December 31, 2023, the company had 23.2 million in cash and cash equivalents.
Outlook
Looking ahead, Theriva Biologics remains focused on driving its clinical programs forward and exploring opportunities to leverage its novel Albumin Shield Technology and other technologies from its oncolytic virus discovery platform. The company expects research and development expenses to increase as it continues enrollment in the VIRAGE trial, advances its VCN-01 program in retinoblastoma, expands GMP manufacturing activities for VCN-01, and supports its VCN-11 and other preclinical and discovery initiatives.
Liquidity
With a cash runway into the first quarter of 2025, Theriva Biologics believes it is well-positioned to execute on its corporate objectives and achieve multiple value-enhancing milestones, including completing enrollment for the VIRAGE study in the first half of 2024, completing follow-up in the Phase 1 investigator-sponsored trial evaluating intravitreal VCN-01 in pediatric patients with refractory retinoblastoma in the first half of 2024, and completing enrollment in the second cohort of the Phase 1b/2a clinical study of SYN-004 for the prevention of aGVHD in bone marrow transplant patients in the second quarter of 2024.
Conclusion
Theriva Biologics' transition to an oncology-focused company, coupled with the promising data and progress across its pipeline, positions the company well to address significant unmet needs in difficult-to-treat cancers. As the company continues to execute on its strategic priorities, investors will closely monitor the advancement of VCN-01 and the potential value-creating opportunities that may arise from the company's broader oncology portfolio and novel technology platforms.