GEN2 / GenVivo - LARVOL DELTA

Phase 1 Study of GEN2, A Personalizing Gene Therapy Vector, in Adult Patients with Locally Advanced or Metastatic Solid Tumor Malignancies (ASGCT 2025) - P1 | "When transduced into a tumor cell and in the presence of the oral prodrug ganciclovir (VGCV), HSV-eTK triggers cancer cell death by DNA chain termination and subsequent release of the full complement of unique tumor antigens including neoantigens (NA). Once the IV RP2D is identified, the protocol will open three expansion arms: hepatocellular carcinoma, HR+ breast and cutaneous malignancies (NCT06391918). Disease Focus of Abstract:Cancer Solid Tumors"

Clinical • Gene therapy • Metastases • P1 data • Dermatology • Gene Therapies • Hepatocellular Cancer • Hormone Receptor Breast Cancer • Liver Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Skin Cancer • Solid Tumor • CSF2

Safety and efficacy evaluation of retroviral vectors GEN-1018 and GEN-1013 toward clinical translation for in vivo immuno-gene therapy and combined suicide gene therapy (ASGCT 2025) - "Our previous preclinical studies supported initiation of clinical trials for in vivo cancer gene therapy with GEN2, a retroviral vector for combined delivery of granulocyte-macrophage colony stimulating factor (GM-CSF) and an enhanced gain-of-function variant of the herpes simplex virus thymidine kinase suicide gene (HSV-eTK)...Preliminary evaluation of therapeutic efficacy was performed by intratumoral (IT) or systemic (IV) administration of mGEN-1018 and mGEN-1013 to subcutaneous CT26 murine colorectal cancer models in syngeneic BALB/c mice, with mGEN-1013 experimental arms also treated with ganciclovir (GCV) prodrug...Based on these results, GEN-1013 is currently being further evaluated in definitive preclinical studies to support clinical translation and Investigational New Drug (IND) application. Disease Focus of Abstract:Cancer Solid Tumors"

Gene therapy • Preclinical • Viral vector • Colorectal Cancer • Gene Therapies • Herpes Simplex • Melanoma • Oncology • Solid Tumor • CSF2 • GZMB • IFNG • IL12A

GenVivo Highlights GEN2 Phase 1 Data...at the 2025 American Society of Gene + Cell Therapy (ASGCT) Annual Meeting (GlobeNewswire) - P1 | N=124| NCT06391918 | Sponsor: GenVivo, Inc. | "GEN2 has minimal toxicity and no Dose Limiting Toxicities (DLTs) over the IV dose ranges (3.4E6 TU/kg to 2E8 TU/kg) to date; Signs of pharmacodynamic activity including GM-CSF levels and vector persistence in peripheral blood mononuclear cells (PBMCs), are observed during the dosing cycle. Once the Recommended Phase 2 Dose (RP2D) is established, the protocol will open three expansion arms: hepatocellular carcinoma (HCC), hormone positive breast cancer, and cutaneous malignancies. Assessment of paired biopsies is underway; Additional cohorts will be initiated with GEN2 in combination with a checkpoint inhibitor (CPI-refractory melanoma, HCC)."

P1 data • Trial status • Breast Cancer • Hepatocellular Cancer • Hormone Receptor Positive Breast Cancer • Melanoma • Skin Cancer

Phase 1 Study of GEN2 in Patients with Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: GenVivo, Inc. | N=91 ➔ 124

Enrollment change • Metastases • Oncology • Solid Tumor

A phase 1 clinical trial of GEN2, a personalizing gene vector immunotherapy, in combination with valganciclovir in adult patients with hepatocellular carcinoma or tumors metastatic to liver (SITC 2024) - P1 | "Luke's Medical Center Institutional Ethics Review Committee • Manila Doctors Hospital Institutional Review Board The IRB/IECs were appropriately constituted and operated in accordance with the Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6(R2). Patients provided written informed consent before any study-specific tests or procedures were performed."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CSF2

GenVivo to Present Phase 1 Trial Results for GEN2, A Personalizing Gene Vector Therapy, at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - P1 | N=61 | NCT04313868 | Sponsor: GenVivo, Inc. | "GEN2 demonstrated tolerability and minimal toxicity, with no dose-dependent Treatment Emergent Adverse Events (TEAEs). Linear exposure was observed across the 1000-fold dose range. Twenty-one percent of patients remained on therapy for longer than 6 months with the longest up to 21 months. A toxicity-defined maximum tolerated dose (MTD) has not been identified."

P1 data • Hepatocellular Cancer

GEN2 Directed Cancer Immunotherapy Trial (clinicaltrials.gov) - P1 | N=61 | Completed | Sponsor: GenVivo, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Dec 2023 | Trial primary completion date: Jun 2024 ➔ Dec 2023

Metastases • Trial completion • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor

GenVivo Announces Initiation of Patient Dosing in a US Phase I/Ib Clinical Trial Evaluating GEN2, a Personalizing, Gene Vector Immunotherapy, in Patients with Advanced Solid Tumors (GlobeNewswire) - "GenVivo...announced that it has dosed the first US patient in a Phase I/Ib, open-label, dose-escalation and expansion clinical trial of GEN2....This GEN2 Phase I/Ib, dose-escalation clinical trial (NCT06391918) is currently enrolling US patients with advanced solid tumors who have progressed or were non-responsive to prior therapies. The clinical trial is primarily designed to assess the safety and tolerability of GEN2 and to establish the recommended Phase II dose (RP2D). Following the initial dose-escalation phase, the expansion phase will explore the RP2D in 3 arms with defined solid tumor types, to further demonstrate safety, tolerability, and signs of clinical activity."

Trial status • Solid Tumor

Phase 1 Study of GEN2 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=91 | Recruiting | Sponsor: GenVivo, Inc.

Metastases • New P1 trial • Oncology • Solid Tumor

Serial assessment of GEN2, a retroviral vector for gene transfer of an optimized thymidine kinase and GM-CSF, for genomic integration into peripheral blood mononuclear cells (PBMCs) in a Phase 1 clinical trial in adult patients with solid tumors (AACR 2024) - P1 | "GEN2 in combination with valganciclovir (an oral formulation of GCV) was evaluated in a dose-escalating Phase 1 clinical trial in 61 adult patients (pts) with an advanced solid tumor (NCT04313868), with serial assessment of PBMCs to detect any GEN2 integration and replication competent retrovirus (RCR). All 82 samples obtained from the intravenous cohorts 1-12 were below LOD (Limit of Detection) for RCR. All results for integration were BLOQ (Below Limit of Quantitation), whereas 4 samples collected at two hours following the end of infusion were above LOD, likely resulting from non-integrated cDNA. GEN2 continues to be studied in clinical trials in adult patients with solid tumors."

Clinical • P1 data • Viral vector • Oncology • Solid Tumor • CSF2

GEN2 Directed Cancer Immunotherapy Trial (clinicaltrials.gov) - P1 | N=61 | Active, not recruiting | Sponsor: GenVivo, Inc. | Recruiting ➔ Active, not recruiting | N=122 ➔ 61 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Enrollment change • Enrollment closed • Metastases • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

GEN2 Directed Cancer Immunotherapy Trial (clinicaltrials.gov) - P1 | N=122 | Recruiting | Sponsor: GenVivo, Inc. | Trial completion date: Mar 2023 ➔ Jun 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Optimization of a Suicide Gene Vector for the GEN2 Cancer Immunotherapy Clinical Trial (ASGCT 2023) - "The optimization of a suicide gene which serves to unmask neoantigens within tumor cells and generate immune activation was undertaken using a series of criteria focused on more effective distribution of the suicide gene within the tumor cells and better selectivity for the prodrug, ganciclovir (GCV)...HSV-TK is an enzyme that locally converts an orally administered prodrug activator (valganciclovir) into a toxic cellular metabolite that ultimately induces cell death in transduced and nearby cancer cells, release of neoantigens into the tumor microenvironment and activation of local and system immune responses...Overall, the combination of all modifications renders GEN2 more potent in cancer cell killing compared to all other vectors tested. GEN2 (HSV-TK-GMCSF) is currently being evaluated in a Phase I clinical trial."

Clinical • IO biomarker • Hematological Malignancies • Herpes Simplex • Leukemia • Oncology • CSF2

GEN2 Directed Cancer Immunotherapy Trial (clinicaltrials.gov) - P1 | N=122 | Recruiting | Sponsor: GenVivo, Inc. | Trial completion date: Jul 2022 ➔ Mar 2023 | Trial primary completion date: Mar 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

GEN2 Directed Cancer Immunotherapy Trial (clinicaltrials.gov) - P1; N=122; Recruiting; Sponsor: GenVivo, Inc.; Trial completion date: Feb 2021 ➔ Jul 2022; Trial primary completion date: Oct 2020 ➔ Mar 2022

Clinical • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Neutropenia • Oncology • Solid Tumor