zabilugene almadenorepvec (VCN-01) / Theriva Bio - LARVOL DELTA

Theriva Biologics Reports Third Quarter 2025 Operational Highlights… (GlobeNewswire) - "'Having successully completed the VIRAGE Phase 2b clinical trial, we are now pursuing interactions with the European Medicines Agency and the US FDA to seek alignment on a protocol for a proposed Phase 3 study of VCN-01 plus gemcitabine/nab-paclitaxel standard-of-care chemotherapy as first-line treatment for metastatic PDAC. In addition, we have made significant progress on the design of a potential Phase 2/3 clinical trial in the rare pediatric disease retinoblastoma for potential discussion with regulators in the first half of 2026'."

Clinical protocol • Regulatory • Pancreatic Ductal Adenocarcinoma • Retinoblastoma

Preclinical data for VCN-12 was presented at the ESGCT 32nd Annual Congress (GlobeNewswire) - "Data presented at ESGCT showed that VCN-12 provided increased cell killing compared to VCN-01 in a variety of cancer cell models in vitro and displayed higher levels of hyaluronidase activity. In animal studies, intravenous VCN-12 had a similar toxicity profile to VCN-01 in immunodeficient mice bearing human tumor xenografts....Additional preclinical studies to confirm these findings are ongoing."

Preclinical • Oncology

VIRAGE trial: Randomized phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC) (ESMO 2025) - P2 | "Conclusions This study met its primary endpoints. Patients receiving VCN-01 + GA had improved OS, PFS and DoR compared to GA SoC."

Clinical • Metastases • P2b data • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9

VCN-01 with Standard Care Boosts Survival, Shows Safety in PDAC (Cure Today) - "Median OS in the modified intent-to-treat (mITT) population was 10.6 months versus 8.6 months in the VCN-01 and SOC arms, respectively. The full analysis set (FAS) population yielded a median OS of 10.8 months versus 8.6 months, respectively. Patients receiving VCN-01 had a median DOR of 11.2 months versus 5.4 months in the SOC arm."

P2b data • Pancreatic Ductal Adenocarcinoma

Theriva Biologics Announces Presentation Describing Next Generation Oncolytic Adenovirus VCN-12 at the 32nd Annual Congress of the European Society of Gene & Cell Therapy (ESGCT) (GlobeNewswire) - "Co-founder of VCN Biosciences...will present new mechanistic and preclinical data for VCN-12, a next generation oncolytic adenovirus selected from Theriva’s VCN-X discovery program....In addition to the scheduled presentation on VCN-12, a recently-published pre-ESGCT meeting monograph details the results of a preclinical study conducted by investigators at the University of Navarra evaluating the intracranial administration of VCN-01 for the potential treatment of brain tumors."

Preclinical • Brain Cancer

Theriva Biologics Reports Second Quarter 2025 Operational Highlights and Financial Results (GlobeNewswire) - "Expanded data from the VIRAGE trial are to be presented at a mini oral session at the European Society for Medical Oncology (ESMO) 2025 Congress. The presentation...(abstract 2216MO) is planned to be presented on Monday, October 20, 2025..."

P2b data • Pancreatic Ductal Adenocarcinoma

Toxicity and Biodistribution of the Oncolytic Virus VCN-01 Following Intracranial Injection in Syrian Hamsters. (PubMed, Hum Gene Ther) - "The neutralizing antibody response against the virus was stronger in females than in males, correlating with a lower detection of vp in females compared with males. In conclusion, these findings support the safety of intracranial administration of VCN-01 and provide a strong rationale for its further development as a therapeutic option for patients with brain tumors."

Journal • Brain Cancer • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor

Second Quarter Ended June 30, 2025 Financial Results (GlobeNewswire) - "General and administrative expenses increased to $11.2 million for the three months ended June 30, 2025....This increase of 662% is primarily comprised of the increase in fair value of the contingent consideration adjustment of $9.2 million due to the VIRAGE Phase 2b clinical trial of VCN-01 in PDAC achieving its primary endpoint and increased registration fees."

Commercial • Pancreatic Ductal Adenocarcinoma

A phase I dose-escalation study to assess the oncolytic virus VCN-01 safety and efficacy in refractory retinoblastoma patients. (ASCO 2025) - P=N/A | "VCN01 was safe, being uveitis the most common adverse effect. VCN-01 did not cause retinal toxicity. The response in these heavily pre-treated eyes was encouraging."

Clinical • Oncolytic virus • P1 data • Eye Cancer • Glaucoma • Ocular Inflammation • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • Uveitis

Theriva Biologics Announces Presentation of Data from VCN-01 Retinoblastoma Phase 1 Clinical Trial at ASCO 2025 and Investigator Meeting to Review Topline Data from the VIRAGE Phase 2b Trial of VCN-01 in Metastatic Pancreatic Cancer (The Manila Times) - "Theriva Biologics...today announced the upcoming presentation of final clinical outcomes and safety data from the investigator sponsored Phase 1 clinical study conducted at Sant Joan de Déu Barcelona Children’s Hospital evaluating the safety and tolerability of two intravitreal injections of VCN-01 (zabilugene almadenorepvec) in patients with intraocular retinoblastoma that was refractory to systemic, intra-arterial, or intravitreal chemotherapy, and for whom enucleation was the only recommended treatment....Theriva senior management will also attend the ASCO conference and participate in an off-site meeting on Monday June2nd, 2025 to review the recently reported topline results of the VIRAGE Phase 2b clinical trial in first-line metastatic pancreatic ductal adenocarcinoma (PDAC) with investigators and garner additional insights relevant to the design and execution of a Phase 3 clinical trial in this indication."

New P3 trial • P1 data • P2b data • Pancreatic Ductal Adenocarcinoma • Retinoblastoma

Theriva Biologics Reports First Quarter 2025 Operational Highlights and Financial Results (GlobeNewswire) - "Research and development expenses decreased to $3.0 million for the three months ended March 31, 2025, from approximately $3.5 million for the three months ended March 31, 2024. This decrease of 14% is primarily the result of lower indirect cost related to decreased VCN-01 manufacturing costs and lower clinical trial expenses related to our Phase 1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic HCT recipients, offset by slightly higher clinical trial expenses related to our VIRAGE Phase 2b clinical trial of VCN-01 in PDAC and higher patent expenses related to SYN-020. We anticipate research and development expense to increase as we complete our VIRAGE Phase 2b clinical trial of VCN-01 and plan for our Phase 3 clinical trial of VCN-01 in PDAC, advance our VCN-01 program in retinoblastoma, expand GMP scale-up manufacturing activities for VCN-01, and continue supporting our other preclinical and discovery initiatives."

Commercial • Gastrointestinal Disorder • Immunology • Pancreatic Ductal Adenocarcinoma • Retinoblastoma

Theriva Biologics Announces Primary Endpoints for Efficacy and Safety Achieved in VIRAGE Phase 2b Clinical Trial of VCN-01 with Gemcitabine/nab-Paclitaxel in Newly-Diagnosed Metastatic Pancreatic Cancer Patients (GlobeNewswire) - P2b | N=112 | VIRAGE (NCT05673811) | Sponsor: Theriva Biologics SL | "Patients treated with VCN-01 (zabilugene almadenorepvec) plus gemcitabine/nab-paclitaxel standard-of-care (SoC) chemotherapy had increased overall survival, progression free survival, and duration of response compared to patients treated with gemcitabine/nab-paclitaxel SoC; VCN-01 was well-tolerated, with transient and reversible adverse events (AEs), meeting primary safety endpoint; Greater differences between the treatment arms were observed in patients receiving 2 doses of VCN-01; Data to be reviewed during a Key Opinion Leader webinar Featuring Dr. Manuel Hidalgo Medina and Dr. Mike Pishvaian on Wednesday May 7th, 2025 at 0800 US EDT."

P2b data • Pancreatic Cancer

VIRAGE: Study of Nab-Paclitaxel and Gemcitabine and Plus/Minus VCN-01 in Patients With Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=112 | Completed | Sponsor: Theriva Biologics SL | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Theriva Biologics Announces Positive Outcomes from the Second Meeting of the Independent Data Monitoring Committee for VIRAGE, the Company’s Phase 2b Clinical Trial of VCN-01 in Combination with Chemotherapy for Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) (GlobeNewswire) - "Theriva Biologics...today announced that a second Independent Data Monitoring Committee (IDMC) review of data from the VIRAGE Phase 2b clinical trial in newly-diagnosed metastatic pancreatic ductal adenocarcinoma (PDAC) found that that VCN-01 was well tolerated in combination with standard-of-care chemotherapy (gemcitabine/nab-paclitaxel) and the adverse event (AE) profile was as expected for the patient population and the medications being studied....The VCN-01 AE profile was consistent with that observed in prior clinical trials....VIRAGE patient enrollment was completed in September 2024 and topline clinical outcomes data are anticipated in Q2 2025....If positive, these data, in combination with the previously reported feedback from the FDA and EMA, will guide the design of a potential Phase 3 registrational trial for discussion with regulatory agencies later this year."

DSMB • New P3 trial • P2b data • Trial status • Pancreatic Ductal Adenocarcinoma

Theriva Biologics Reports Full-Year 2024 Operational Highlights and Financial Results (GlobeNewswire) - "Recent Program Highlights and Anticipated Milestones: VCN-01 - Pancreatic Ductal Adenocarcinoma (PDAC):...Topline data from the VIRAGE study, and the outcomes of a second Data Monitoring Committee review of safety data, are expected in Q2 2025. In December 2024 we received minutes from a Type D meeting with the FDA and in February 2025 we received scientific advice from the Committee for Human Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), both providing guidance on the design of a potential pivotal Phase 3 clinical study of lead clinical candidate VCN-01 in combination with standard-of-care chemotherapy gemcitabine/nab-paclitaxel for the treatment of metastatic PDAC. Feedback from the FDA and EMA is being incorporated into the design of a Phase 3 study protocol and an End-of-Phase 2 meeting with the FDA to discuss the proposed Phase 3 study will be requested before the end of 2025."

DSMB • New P3 trial • P2b data • Pancreatic Ductal Adenocarcinoma

Theriva Biologics Announces U.S. FDA Guidance on Design of Phase 3 Study of VCN-01 for the Treatment of Metastatic Pancreatic Cancer (GlobeNewswire) - "Theriva Biologics...today announced the outcomes of a recent Type D meeting with the U.S. Food and Drug Administration (FDA) to obtain guidance on the design of a Phase 3 clinical study of lead clinical candidate VCN-01 in combination with standard-of-care chemotherapy for the treatment of metastatic pancreatic adenocarcinoma (PDAC)....The FDA advised that the on-going VIRAGE Phase 2b study should not be expanded into a Phase 3 study; rather, the optimal path forward for the VCN-01 PDAC program is to conduct a stand-alone Phase 3 study of VCN-01 with gemcitabine/nab-paclitaxel....An additional meeting with the FDA will be requested after the completion of the VIRAGE study to discuss the details of the proposed confirmatory Phase 3 study protocol."

FDA event • New P3 trial • Pancreatic Ductal Adenocarcinoma

huCART-meso + VCN-01 in Pancreatic and Ovarian Cancer (clinicaltrials.gov) - P1 | N=13 | Active, not recruiting | Sponsor: University of Pennsylvania | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Hepatology • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Third Quarter Ended September 30, 2024 Financial Results (GlobeNewswire) - "Research and development expenses decreased to $2.7 million for the three months ended September 30, 2024, from approximately $4.0 million for the three months ended September 30, 2023. This decrease of 32% is primarily the result of lower clinical trial expenses related to our VIRAGE Phase 2 clinical trial of VCN-01 in PDA....We anticipate research and development expense to increase as we continue our VIRAGE Phase 2 clinical trial of VCN-01 and plan for our Phase 3 clinical trial of VCN-01 in PDAC, advance our VCN-01 program in retinoblastoma, expand GMP manufacturing activities for VCN-01, and continue supporting our other preclinical and discovery initiatives."

Commercial • Eye Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Retinoblastoma • Solid Tumor

Recent Program Highlights and Anticipated Milestones (GlobeNewswire) - "Target of 92 evaluable patients (46 in each of the control and VCN-01 treatment arms) enrolled across 15 sites in Spain and the USA within 21 months in VIRAGE, the randomized, controlled, multicenter, open-label Phase 2b trial of VCN-01 in combination with standard-of-care chemotherapy (gemcitabine/nab-paclitaxel) as a first line therapy in newly diagnosed metastatic PDAC patients...Initiated discussions with regulatory agencies to explore the potential expansion of the VIRAGE Phase 2b study into a Phase 3 registrational trial....The investigator sponsored Phase 1 trial evaluating the safety and activity of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma has completed treatment and follow-up and the clinical study report is in preparation. The results of the study were determined to be positive by the study Monitoring Committee and discussions with key opinion leaders worldwide, as well as with regulatory agencies, are ongoing to refine our..."

Trial status • Eye Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Retinoblastoma • Solid Tumor

Theriva Biologics Selected as Finalist in International Competition for Merck KGaA's EMEA Advance Biotech Grant (GlobeNewswire) - "Manel Cascalló, PhD., General Director - EU Subsidiary, Theriva Biologics, will present an overview of VCN-01, currently being studied in a Phase 2b clinical trial in first-line metastatic pancreatic cancer in combination with standard-of-care chemotherapy. Dr Cascalló will highlight VCN-01’s novel mechanisms of action and Theriva’s internal capabilities to develop its manufacturing process in his presentation on Monday, November 4, 2024 from 15:20-16:40 CET/CEST (GMT+2)."

Clinical • Commercial • Oncology • Pancreatic Cancer

Theriva Biologics Announces Orphan Medicinal Product Designation Granted by the European Commission to VCN-01 for the Treatment of Retinoblastoma (GlobeNewswire) - "Theriva Biologics...announced that the European Commission has adopted the European Medicines Agency (EMA) recommendation to grant orphan medicinal product designation to lead clinical candidate VCN-01, Theriva’s systemic, selective, stroma-degrading oncolytic adenovirus, for the treatment of retinoblastoma....'We have previously reported encouraging results from an investigator sponsored Phase 1 trial evaluating the safety and activity of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma, and we are working closely with leading physicians and regulatory agencies worldwide to refine our clinical strategy for VCN-01 as an adjunct to chemotherapy in children with this challenging disease'."

Orphan drug • Retinoblastoma

VIRAGE: Study of Nab-Paclitaxel and Gemcitabine and Plus/minus VCN-01 in Patients with Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=96 | Active, not recruiting | Sponsor: Theriva Biologics SL | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Theriva Biologics Achieves Target Patient Enrollment in the VIRAGE Phase 2b Trial of VCN-01 with Gemcitabine/nab-Paclitaxel for the Treatment of Metastatic Pancreatic Cancer (GlobeNewswire) - "Theriva Biologics, Inc...announced that it has achieved their target patient enrollment in the VIRAGE Phase 2b clinical trial evaluating the Company’s lead product candidate VCN-01 plus standard-of-care (SoC) chemotherapy (gemcitabine/nab-paclitaxel) as a first line therapy for patients with metastatic pancreatic ductal adenocarcinoma (PDAC)."

Enrollment closed • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

RTB: Evaluate Safety and the Oncolitic Adenovirus VCN-01 Activity in Patients With Refractory Retinoblastoma (clinicaltrials.gov) - P=N/A | N=13 | Completed | Sponsor: Fundació Sant Joan de Déu | Active, not recruiting ➔ Completed

Oncolytic virus • Trial completion • Eye Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • RB1

Theriva Biologics Reports Second Quarter 2024 Operational Highlights and Financial Results (GlobeNewswire) - "VCN-01: Dosing is underway and enrollment is nearing completion for VIRAGE, the randomized, controlled, multicenter, open-label Phase 2b trial of VCN-01 in combination with standard-of-care chemotherapy (gemcitabine/nab-paclitaxel) as a first line therapy in newly diagnosed metastatic PDAC patients. The trial intends to enroll 92 evaluable patients across sites in the U.S. and Spain, and is expected to complete enrollment in the third quarter of 2024; Results from the investigator sponsored Phase 1 trial evaluating the safety and activity of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma were determined to be positive by the study Monitoring Committee."

DSMB • Enrollment status • Gastrointestinal Cancer • Pancreatic Adenocarcinoma • Pancreatic Ductal Adenocarcinoma • Retinoblastoma