THERIVA BIOLOGICS Stock Price, News & Analysis

Theriva Biologics, Inc. (NYSE American: TOVX) is a diversified clinical-stage pharmaceutical company focused on developing therapeutics designed to treat cancer and related diseases in areas of high unmet need. The company is advancing programs in oncology and infectious disease, with a particular emphasis on an oncolytic adenovirus platform intended for intravenous (IV), intravitreal and antitumoral delivery. This platform is designed to trigger tumor cell death, improve access of co-administered cancer therapies to tumors, and promote a sustained anti-tumor immune response.

Core therapeutic focus

According to multiple company disclosures, Theriva’s lead clinical-stage candidate is VCN-01 (zabilugene almadenorepvec), a systemically administered oncolytic adenovirus. VCN-01 is designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma, which is described as a significant physical and immunosuppressive barrier to cancer treatment. By degrading this barrier and infecting tumor cells, VCN-01 is intended to exert several antitumor effects: selectively lysing tumor cells, enhancing the access and perfusion of co-administered chemotherapy products, and increasing tumor immunogenicity so that tumors are more visible to the patient’s immune system and to co-administered immunotherapy products.

Systemic administration of VCN-01 is described as enabling activity at both primary tumors and metastases. Company materials state that VCN-01 has been administered to more than 140 patients across clinical trials in multiple cancer types, including pancreatic ductal adenocarcinoma (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 via intravitreal injection.

Lead oncology indications

Theriva reports that VCN-01 has been evaluated in the VIRAGE Phase 2b clinical trial in metastatic pancreatic ductal adenocarcinoma. In this randomized, controlled, multicenter study, patients received standard-of-care gemcitabine/nab-paclitaxel with or without VCN-01. The company has reported that patients in the VCN-01 plus standard-of-care arm demonstrated increased overall survival, progression free survival, and duration of response compared to standard-of-care alone, with greater improvements observed in patients who received two doses of VCN-01 administered three months apart.

Based on these data, Theriva has engaged with the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) regarding the design of a proposed Phase 3 clinical trial of VCN-01 plus gemcitabine/nab-paclitaxel as first-line treatment for metastatic PDAC. Company disclosures state that CHMP scientific advice included agreement on key trial elements such as inclusion and exclusion criteria, primary and secondary endpoints, sample size, and an adaptive design. The advice also acknowledged the observed improvement in overall survival in patients receiving two doses of VCN-01 and supported a dosing strategy using repeated “macrocycles” that could enable more than two doses in Phase 3.

In pediatric oncology, Theriva highlights VCN-01 development in retinoblastoma, a childhood eye cancer. An investigator-sponsored Phase 1 study at Sant Joan de Déu Barcelona Children’s Hospital evaluated intravitreal VCN-01 in patients with intraocular retinoblastoma refractory to systemic, intra-arterial, or intravitreal chemotherapy, where enucleation was the only recommended treatment. The company has reported that a study monitoring committee determined the trial results to be positive, and presentations have described VCN-01 as having a tolerable toxicity profile and encouraging responses in refractory vitreous seeds.

Pipeline beyond VCN-01

In addition to VCN-01, Theriva’s disclosures describe two other lead clinical-stage candidates:

• SYN-004 (ribaxamase), an oral prophylactic therapy designed to degrade certain commonly used IV beta-lactam antibiotics within the gastrointestinal (GI) tract. The stated goal is to prevent microbiome damage, limit overgrowth of pathogenic organisms such as vancomycin-resistant Enterococci (VRE), and reduce the incidence and severity of acute graft-versus-host disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients. Company materials reference a previously completed placebo-controlled Phase 2b trial in 412 patients in which SYN-004 was reported to protect the gut microbiome from antibiotic-mediated dysbiosis and to be associated with better maintenance and recovery of the microbiome and lower incidences of new colonization by opportunistic organisms such as VRE.
• SYN-020, described as a recombinant oral formulation of the enzyme intestinal alkaline phosphatase (IAP) produced under cGMP conditions and intended to treat both local GI and systemic diseases.

Theriva also refers to a VCN-X discovery program, including VCN-12, a next-generation oncolytic adenovirus that uses the same virus capsid as VCN-01 but incorporates modifications intended to increase stroma degradation and tumor cell lysis. Preclinical data presented at a gene and cell therapy congress showed increased cell killing compared to VCN-01 in various cancer cell models, higher hyaluronidase activity, and antitumor effects in animal models, with additional preclinical studies ongoing.

Regulatory designations and development strategy

Company communications state that VCN-01 has received Orphan Drug designation for metastatic PDAC in Europe and the United States, Fast Track designation in the United States for pancreatic cancer, and Orphan Drug and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for retinoblastoma. Theriva indicates that it is using clinical data from VIRAGE and the retinoblastoma Phase 1 study to inform proposed pivotal trials and to support potential future marketing authorization applications, subject to regulatory review and demonstration of an acceptable benefit-risk profile.

Corporate and capital markets profile

Theriva Biologics, Inc. is incorporated in Nevada and its common stock trades on the NYSE American under the symbol TOVX, as reflected in multiple Form 8-K and proxy filings. The company has used a combination of public offerings, at-the-market sales, and warrant-related transactions to fund operations, including a public offering of common stock and warrants and a warrant inducement transaction with institutional investors. Proxy statements and related filings describe efforts to obtain stockholder approval for the potential issuance of additional shares upon exercise of new warrants.

Through its subsidiary Theriva Biologics, S.L., the company reports that it conducts research and clinical development activities related to its oncolytic adenovirus platform. SEC filings and press releases emphasize that Theriva is in the clinical stage, that its product candidates are under investigation, and that development is subject to regulatory review, clinical outcomes, financing, and other risk factors described in its periodic reports.

Business model and industry positioning

Within the pharmaceutical preparation manufacturing industry, Theriva’s disclosed activities center on discovering, developing, and clinically testing novel biologic therapeutics. Revenue-generating commercialization is not described in the provided materials; instead, the company focuses on advancing clinical programs, obtaining regulatory feedback, presenting data at scientific and medical meetings, and pursuing potential partnerships to support late-stage development and manufacturing scale-up of its candidates.

According to its communications, Theriva’s work spans oncology indications such as metastatic pancreatic ductal adenocarcinoma, head and neck squamous cell carcinoma, ovarian cancer, colorectal cancer, and retinoblastoma, as well as infectious disease and transplant-related complications through SYN-004. The company’s disclosures consistently highlight areas of high unmet medical need and the intent to improve patient outcomes by combining its investigational agents with existing standards of care.