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

VIRAGE: A phase IIb, open-label, randomized study of nab-paclitaxel and gemcitabine plus/minus VCN-01 in patients with metastatic pancreatic cancer. (ASCO 2024) - P1, P2 | "The secondary objectives include time-to-progression (TTP), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), duration of the response (DoR), 1-year OS and PFS rates, and serial changes in tumor markers (Ca19.9). At 31 Jan 2024, the enrollment is ongoing in US and Spanish sites."

Clinical • Metastases • P2b data • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CA 19-9 • RB1

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

Theriva Biologics…announced the dosing of the first patient in the VIRAGE2 Phase 2a clinical trial, a small proof-of-concept study evaluating more frequent repeated dosing of VCN-01 (zabilugene almadenorepvec) in first-line metastatic PDAC patients treated with standard-of-care gemcitabine/nab-paclitaxel chemotherapy (GlobeNewswire) - "Enrollment into the VIRAGE2 trial is expected to be completed in H2 2026 and initial pharmacodynamic and safety/tolerability data are anticipated by Q3 2027. Results from this trial will inform the VCN-01 dosing regimen for potential evaluation in a future pivotal Phase 3 clinical trial."

P2a data • Trial status • Pancreatic Ductal Adenocarcinoma

VIRAGE2: A Study of More Frequent Dosing of VCN-01 Combined With Standard Chemotherapy in Patients With Newly Diagnosed Metastatic Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=6 | Recruiting | Sponsor: Theriva Biologics SL | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

VIRAGE2: A Study of More Frequent Dosing of VCN-01 Combined With Standard Chemotherapy in Patients With Newly Diagnosed Metastatic Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=6 | Not yet recruiting | Sponsor: Theriva Biologics SL

New P1/2 trial • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Theriva Biologics…announced that the Spanish Agency of Medicines and Medical Devices (AEMPS) has authorized the Company to initiate the VIRAGE2 clinical trial… (GlobeNewswire) - "The VIRAGE2 trial is designed to evaluate the feasibility of administering at least 3 doses of VCN-01 given 2 months apart in combination with SoC chemotherapy....Results from this trial will inform the VCN-01 dosing regimen for potential evaluation in a future pivotal Phase 3 clinical trial....VIRAGE2 is a Phase 2a, single-arm, open-label, clinical trial in 6 evaluable patients with histologically confirmed, newly diagnosed metastatic PDAC enrolled at a single site in Spain."

New P2a trial • Pancreatic Ductal Adenocarcinoma

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

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 Announces Results from VCN-01 Phase 1 Clinical Trial in Head and Neck Cancer Published in Clinical Cancer Research (The Manila Times) - "Median progression-free survival (PFS) was 1.6 months in Arm I LD, 3.7 months in Arm II LD, and 2.1 months in Arm II HD; Median overall survival (OS) was 10.3 months in Arm I LD, 15.5 months in Arm II LD, and 17.3 months in Arm II HD; Circulating levels of the stroma-degrading hyaluronidase enzyme PH20 (expressed during selective VCN-01 intratumoral replication) increased significantly after VCN-01 administration in all tested patients, peaking on day 3-8 for most patients and detectable until day 28 in 11 of 12 patients....Tumor biopsies revealed upregulation of PD-1 and PD-L1 in most patients following VCN-01 administration that correlated with patient survival, suggesting that immune system activity and heightened PD-L1 expression in tumors contributed to the improved outcomes from VCN-01 and durvalumab combination."

P1 data • Squamous Cell Carcinoma of Head and Neck

Phase I trial of intravenous VCN-01 oncolytic adenovirus and durvalumab in patients with head and neck metastatic squamous cell carcinoma refractory to immunotherapy. (PubMed, Clin Cancer Res) - "Sequential VCN-01 plus durvalumab was better tolerated than concomitant treatment. The recommended VCN-01 phase 2 dose (RP2D) was 1.0E13 vp, on the sequential schedule. Encouraging survival was observed in patients after progressing on anti-PD-(L)1 agents. Data supports VCN-01 replication associated with increased PD-1, PD-L1, and CD8 tumor expression. Sequential systemic delivery of VCN-01 and anti-PD-L1 therapy may represent an improved treatment for HNSCC."

IO biomarker • Journal • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • PD-1

A SYSTEMATIC REVIEW OF ONCOLYTIC VIRUSES AND GENE THERAPIES FOR RETINOBLASTOMA IN CHILDREN (ISPOR 2026) - "In one study, targeted vitreous seeds were resolved in all 8 children treated intravitreally with adenoviral vectors containing a herpes thymidine kinase gene followed by intravenous ganciclovir...A second study reported partial responses in 5/9 children with retinoblastoma treated with the oncolytic adenovirus VCN-01... Although oncolytic viruses and gene therapies are regarded as experimental in children with retinoblastoma, early clinical trials have demonstrated their potential efficacy and safety for intraocular use. Larger, long-term controlled studies are needed to further validate Phase I results."

Clinical • Gene therapy • IO biomarker • Oncolytic virus • Review • Eye Cancer • Gene Therapies • Ocular Inflammation • Retinal Disorders • Retinoblastoma • Solid Tumor • RB1

Theriva Biologics Reports First Quarter 2026 Operational Highlights and Financial Results (GlobeNewswire) - "VCN-01 administered to retinoblastoma patients under a compassionate use program, which is expected to provide dosing feasibility and tolerability data for a potential Phase 2/3 clinical trial....'We expect that outcomes from these compassionate use patients will provide valuable information on the feasibility and tolerability of this combination for use in a potential Phase 2/3 clinical trial. If a protocol is ultimately submitted to, and agreed by, the FDA, we expect the first patient to be enrolled in December 2026, with rolling Biologic Licensing Application (BLA) submissions expected to be made in 2029 (if successful), targeting potential approval of the BLA prior to September 30, 2029.'"

FDA approval • FDA filing • New P2/3 trial • Retinoblastoma

Analysis of tumor and biomarker responses in the VIRAGE Trial, a randomized Phase IIb, open-label, study of nab-paclitaxel and gemcitabine with/without intravenous VCN-01 in patients with metastatic pancreatic cancer (mPDAC) (AACR 2026) - "Compared to patients in Arm I (GA), mPDAC patients in Arm II (VCN-01+GA) showed improved OS and PFS and later and more durable responses. Patients that received a second VCN-01 dose+GA showed a further delayed disease progression and extended patient survival compared to patients that received equivalent cycles of GA."

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

Theriva Biologics Announces Upcoming Presentation of Additional Data from the VIRAGE Phase 2b Clinical Trial of VCN-01 in Metastatic Pancreatic Cancer at AACR 2026 Annual Meeting (GlobeNewswire) - "'Taken together, the tumor response and biomarker data support an immune-mediated mode of action for VCN-01, which is consistent with the previously reported clinical observations, showing that patients treated with VCN-01 plus gemcitabine/nab-paclitaxel experienced a significantly protracted duration of response concomitant with a later-stage prolongation of survival compared to patients treated with gemcitabine/nab-paclitaxel alone. We have achieved alignment with both the FDA and the EMA on a proposed pivotal Phase 3 clinical trial to evaluate multiple doses of VCN-01 plus gemcitabine/nab-paclitaxel in first-line metastatic PDAC patients, and we are planning a small study to assess whether more frequent and extended VCN-01 dosing could further improve outcomes'."

European regulatory • FDA event • New trial • P2b data • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Theriva Biologics Announces Positive End-of-Phase 2 Meeting with U.S. FDA Regarding the Design of a Phase 3 Trial of VCN-01 in Metastatic Pancreatic Ductal Adenocarcinoma (The Manila Times) - "The FDA provided general agreement with Theriva’s proposed design for a Phase 3 clinical trial...Theriva to plan the Phase 3 trial to include repeat dosing and an adaptive design aimed to optimize the trial’s timelines and outcomes...The FDA further agreed on the proposed dosing of VCN-01 and gemcitabine/nab-paclitaxel in repeated 'macrocycles' (enabling more than 2 doses of VCN-01 to be administered in the Phase 3 trial), the proposed inclusion/exclusion criteria, the primary endpoint (overall survival), key secondary endpoints (including progression free survival), and the use of an adaptive design."

FDA event • New P3 trial • Pancreatic Ductal Adenocarcinoma

Recent Highlights and Anticipated Milestones (The Manila Times) - "An End-of-Phase 2 meeting with the FDA is planned for 1H 2026, aiming to finalize the design of a pivotal multinational Phase 3 clinical trial in PDAC; Additional analysis from the VIRAGE Phase 2b study has been accepted for a poster presentation at the American Association of Cancer Research (AACR) meeting in San Diego, CA, April 17-22, 2026...Further discussions are planned with both the FDA and EMA in 2026 to align on the protocol design, including target population and endpoints, for a Phase 2/3 trial in retinoblastoma..."

FDA event • New P2/3 trial • New P3 trial • P2b data • Pancreatic Ductal Adenocarcinoma • Retinoblastoma

Theriva Biologics Announces Upcoming Presentation of Data from VCN-01 Retinoblastoma Phase 1 Clinical Trial at APAO 2026 (GlobeNewswire) - "Safety and clinical outcomes of Phase 1 study of VCN-01 (zabilugene almadenorepvec) in refractory retinoblastoma patients to be presented in an invited session at the 41st Asia-Pacific Academy of Ophthalmology (APAO) Congress in Hong Kong on Saturday, 07 February 2026....Preclinical data will highlight synergistic antitumor activity for the combination of topotecan and VCN-01 that may improve outcomes in refractory retinoblastoma patients with difficult-to-treat vitreous seeds."

P1 data • Preclinical • Retinoblastoma

Theriva Biologics Announces Positive Scientific Advice from the European Medicines Agency (EMA) on the Design of a Phase 3 Trial of VCN-01 in Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) (GlobeNewswire) - "Theriva to schedule an End-of-Phase 2 meeting with the FDA in H1 2026 to finalize the design of a pivotal multinational Phase 3 clinical trial...CHMP advised that a potential future marketing authorization application (MAA) for VCN-01 in metastatic PDAC could be supported by Theriva’s proposed clinical development strategy comprising a single, high-quality, double-blinded, randomized, placebo-controlled Phase 3 trial if it demonstrates a compelling benefit-risk ratio with VCN-01 plus gemcitabine/nab-paclitaxel SoC compared to gemcitabine/nab-paclitaxel SoC alone....'In addition to regulatory advice on the proposed PDAC Phase 3 clinical trial, interactions with EMA and FDA are planned in 2026 to seek advice on a potential Phase 2/3 trial for VCN-01 in retinoblastoma...'"

CHMP • FDA event • New P2/3 trial • New P3 trial • Pancreatic Ductal Adenocarcinoma • Retinoblastoma

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

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