sturlimogene erparepvec (RP2) / Replimune - LARVOL DELTA

Safety, efficacy, and biomarker results from an open-label, multicenter, phase 1 study of RP2 alone or combined with nivolumab in a cohort of patients with uveal melanoma. (ASCO 2024) - P1 | "RP2 alone or combined with nivo demonstrated a favorable safety profile and meaningful antitumor activity in pts with previously treated MUM. Biomarker data indicated immune cell infiltration and increased PD-L1 expression in tumors and changes in the peripheral T-cell repertoire following RP2 ± nivo therapy. Based on these results, a randomized, controlled clinical development plan is being planned."

Biomarker • Clinical • IO biomarker • P1 data • Dermatology • Eye Cancer • Fatigue • Genito-urinary Cancer • Hypotension • Melanoma • Oncology • Pruritus • Solid Tumor • Uveal Melanoma • CD8 • PD-L1

Program Highlights & Milestones (The Manila Times) - "IGNYTE-3 Confirmatory Study: The global Phase 3 trial assessing RP1 in combination with nivolumab versus physician's choice in patients with advanced melanoma who have progressed on anti-PD-1 and anti-CTLA-4 therapies or are ineligible for anti-CTLA-4 treatment is actively enrolling. The primary endpoint, expected to readout in 2030, is overall survival, and key secondary endpoints are progression free survival and overall response rate....REVEAL Study: The registration-directed Phase 2/3 trial of RP2 in metastatic uveal melanoma is actively enrolling....Phase 2/3 transition is expected in Q1 2027."

P3 data • Trial status • Melanoma • Uveal Melanoma

WITHDRAWN: A multicenter, open-label study of RP2 oncolytic immunotherapy expressing anti–CTLA-4 combined with second-line atezolizumab plus bevacizumab in advanced hepatocellular carcinoma (HCC) or with first-line durvalumab in advanced biliary tract cancer (BTC). (ASCO 2026) - P2 | "Funded by Replimune, Inc. Clinical Trial Registration Number: NCT05733598 Abstract withdrawn."

Clinical • Metastases • Oncolytic virus • Biliary Cancer • Biliary Tract Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

RPx: A Study to Assess the Long-term Safety Outcomes in Patients Previously Treated With RP1, RP2, or RP3 (clinicaltrials.gov) - P4 | N=50 | Recruiting | Sponsor: Replimune Inc. | Phase classification: P ➔ P4

Phase classification • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor

Replimune Presents Final First-in-Human Data for RP2 in Advanced Solid Tumors During Oral Presentation at the 2026 American Society of Clinical Oncology Annual Meeting (GlobeNewswire) - "The Phase 1 first-in-human trial enrolled 85 heavily pretreated patients with advanced solid tumors, including uveal melanoma, colorectal cancer, head and neck cancers, pancreatic cancer, cutaneous melanoma, and sarcoma....RP2 monotherapy achieved an objective response rate (ORR) of 19.0% (4/21 evaluable patients), with responses observed in uveal melanoma, esophagogastric adenocarcinoma, chordoma, and mucoepidermoid carcinoma. RP2 in combination with nivolumab achieved an ORR of 19.1% (9/47 evaluable patients), with a disease control rate of 48.9%. In uveal melanoma, where a randomized Phase 2/3 trial is enrolling, the pooled ORR (RP2 in combination with nivolumab and RP2 monotherapy) was 33.3%."

First-in-human • P1 data • Colorectal Cancer • Cutaneous Melanoma • Head and Neck Cancer • Pancreatic Cancer • Sarcoma • Uveal Melanoma

Neoadjuvant Intra-tumoral RP2 and FLOT in Gastroesophageal Adenocarcinoma (clinicaltrials.gov) - P2 | N=34 | Not yet recruiting | Sponsor: Abramson Cancer Center at Penn Medicine | Initiation date: Apr 2026 ➔ Sep 2026

Trial initiation date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

RP2 oncolytic immunotherapy alone and in combination with nivolumab (nivo) in patients with advanced solid tumors: Final safety, efficacy, and biomarker results from the phase 1 first-in-human (FIH) study. (ASCO 2026) - P1, P2/3 | "RP2 ± nivo treatment was well tolerated in pts with both superficial and deep visceral metastases. Durable responses were observed with RP2 monotherapy and RP2 + nivo in heavily pretreated pts with diverse tumors with evidence of systemic anti-tumor immune activity, including tumor reduction in distant non-injected lesions. This study supports the ongoing evaluation of RP2 in pts with UM (NCT06581406) and the planned evaluation in other solid tumors."

Biomarker • Clinical • Combination therapy • First-in-human • IO biomarker • Metastases • Oncolytic virus • P1 data • Chordoma • Cutaneous Melanoma • Gastric Adenocarcinoma • Gastroesophageal Junction Adenocarcinoma • Hypotension • Infectious Disease • Influenza • Melanoma • Oncology • Pruritus • Respiratory Diseases • Sarcoma • Solid Tumor • CD8 • CSF2

Safety and feasibility of intratumoral injection of RP1 or RP2 oncolytic immunotherapies in visceral metastases. (ASCO 2026) - P1, P2 | "Pts received RP1/RP2 for up to 8 doses as monotherapy or in combination with nivolumab IV starting at cycle 2 or 4 for up to 2 years. RP1/2 injections into visceral mets were well tolerated, with a comparable safety profile to liver and lung biopsies performed in other clinical settings. The observed RPx safety profile supports the incorporation of IT injections into deep visceral tumors as part of cancer therapy. All-grade treatment-related adverse events (>15%)."

Clinical • Oncolytic virus • Oncology • Respiratory Diseases • Solid Tumor • CSF2

A randomized, phase 2/3 clinical trial investigating RP2 plus nivolumab vs ipilimumab plus nivolumab in immune checkpoint inhibitor–naïve patients with metastatic uveal melanoma. (ASCO 2026) - P2/3 | "Tebentafusp is FDA-approved for mUM based on survival benefit but is restricted to patients who are HLA-A*02:01 positive, and only ~10% of patients achieve an objective response. The co-primary endpoints are OS and progression-free survival by independent central review using RECIST 1.1. Secondary endpoints are ORR, duration of response, disease control rate, clinical benefit rate, duration of clinical benefit, and safety, including incidence of treatment-emergent adverse events (AEs), serious AEs, and immune-mediated AEs."

Checkpoint inhibition • Clinical • Metastases • P2/3 data • Eye Cancer • Herpes Simplex • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CSF2 • HLA-A

A randomized, phase 2/3 clinical trial investigating RP2 plus nivolumab vs ipilimumab plus nivolumab in immune checkpoint inhibitor–naïve patients with metastatic uveal melanoma (EADO 2026) - P2/3 | "Tebentafusp is FDA-approved for mUM based on survival benefit but is restricted to pts who are HLA-A*02:01 positive, and only ~10% of pts achieve an objective response. Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Annual Meeting (Abstract number: TPS9597)."

Checkpoint inhibition • Clinical • Metastases • P2/3 data • Eye Cancer • Herpes Simplex • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma • HLA-A

Replimune to Present at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "The Company has two abstracts selected for oral presentation, including a 3-year landmark overall survival analysis from the IGNYTE clinical trial of RP1 (vusolimogene oderparepvec) plus nivolumab in anti-PD-1 failed melanoma, and an oral presentation on the final safety, efficacy, and biomarker results from the Phase 1 first-in-human study of RP2 alone and combined with nivolumab in advanced solid tumors. Four additional posters for RP1 and RP2 will be presented."

Clinical data • First-in-human • Biliary Tract Cancer • Hepatocellular Cancer • Melanoma • Solid Tumor • Uveal Melanoma

Enhanced CD8+T-cell infiltration, PD-L1 expression, and T-cell repertoire expansion in patients with metastatic uveal melanoma responding to treatment with RP2 alone or in combination with nivolumab (AACR 2024) - P1 | "Correlations between baseline tumor PD-L1 and CD8 expression, HLA type, prior treatment with ipilimumab (ipi)/nivo, and HLA status—vs clinical response status—were assessed. As of August 2022, 17 pts with MUM were enrolled (RP2 monotherapy, n = 3; RP2 + nivo, n = 14). Preliminary RP2 + nivo data demonstrated meaningful antitumor activity in pts with MUM. Biomarker data indicated a conversion of the TME from an immune-excluded to an immune-infiltrated phenotype in responding patients following treatment with RP2 + nivo. Furthermore, systemic peripheral T-cell clonal expansion was noted."

Clinical • Combination therapy • IO biomarker • Metastases • Eye Cancer • Hematological Malignancies • Leukemia • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CD8 • CSF2 • PD-L1

RP2-202: A Randomized, Phase 2/3 Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult Patients With Metastatic Uveal Melanoma (clinicaltrials.gov) - P2/3 | N=280 | Not yet recruiting | Sponsor: Replimune Inc.

Checkpoint inhibition • New P2/3 trial • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

RP2-001-18: Study of RP2 Monotherapy and RP2 in Combination With Nivolumab in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Replimune Inc. | Trial completion date: Apr 2028 ➔ Oct 2026 | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Monotherapy • Trial completion date • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor

RP2-202: A Randomized, Phase 2/3 Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult Patients With Metastatic Uveal Melanoma (clinicaltrials.gov) - P2/3 | N=280 | Recruiting | Sponsor: Replimune Inc. | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

RPL-123-01: A Study to Assess the Long-term Safety Outcomes in Patients Previously Treated With RP1, RP2, or RP3 (clinicaltrialsregister.eu) - P4 | N=41 | Not yet recruiting | Sponsor: Replimune Group Inc.

New P4 trial • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor

RP2/RP3 in Combination With Atezolizumab and Bevacizumab for the Treatment of Patients With CRC (clinicaltrials.gov) - P2 | N=5 | Terminated | Sponsor: Replimune Inc. | Trial completion date: Mar 2027 ➔ Aug 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2027 ➔ Aug 2025; Business reasons.

Mismatch repair • pMMR • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Oncology • Solid Tumor • EGFR

The registration-directed Phase 2/3 trial of RP2 in metastatic uveal melanoma is actively enrolling. (The Manila Times) - "The primary endpoints of the trial are overall survival and progression free survival, and key secondary endpoints are overall response rate and disease control rate. Phase 2/3 transition is expected in Q1 2027, with PFS analysis potentially supporting accelerated approval."

Trial status • Uveal Melanoma

The Phase 2 clinical trial of RP2 combined with atezolizumab and bevacizumab in anti-PD-1/PD-L1 progressed hepatocellular carcinoma is currently enrolling. (The Manila Times) - "The protocol was amended to include RP2 as monotherapy with data planned by the end of 2026. The trial is being conducted under a collaboration and supply agreement with Roche. The Company also has enrolled its first patients in a cohort evaluating RP2 in patients with biliary tract cancer. This cohort will evaluate RP2 combined with durvalumab."

P2 data • Trial status • Biliary Tract Cancer • Hepatocellular Cancer

RPx: A Study to Assess the Long-term Safety Outcomes in Patients Previously Treated With RP1, RP2, or RP3 (clinicaltrials.gov) - P=N/A | N=50 | Recruiting | Sponsor: Replimune Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Melanoma • Oncology • Solid Tumor

Neoadjuvant Intra-tumoral RP2 and FLOT in Gastroesophageal Adenocarcinoma (clinicaltrials.gov) - P2 | N=34 | Not yet recruiting | Sponsor: Abramson Cancer Center at Penn Medicine | Initiation date: Nov 2025 ➔ Apr 2026

Trial initiation date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

A multicenter, open-label study of RP2 oncolytic immunotherapy expressing anti–CTLA-4 in combination with second-line atezolizumab plus bevacizumab in advanced hepatocellular carcinoma (HCC) or in combination with first-line durvalumab in advanced biliary tract cancer (BTC). (ASCO-GI 2026) - P2 | "Pts must be on a combination of gemcitabine, platinum-containing chemotherapy, and a checkpoint inhibitor for ≥12 weeks and have documented stable disease or partial response on ≥2 scans. For both cohorts, the primary endpoint is overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Secondary endpoints include safety, ORR per RECIST 1.1 modified for use in HCC (HCC cohort only), duration of response, complete response rate, progression-free survival, and overall survival."

Clinical • Combination therapy • Metastases • Oncolytic virus • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • MSI

RP2 (GlobeNewswire) - "The Phase 2 clinical trial of RP2 combined with atezolizumab and bevacizumab in anti-PD-1/PD-L1 progressed hepatocellular carcinoma is currently enrolling. The protocol is being amended to include RP2 as monotherapy with data planned by the end of 2026. The trial is being conducted under a collaboration and supply agreement with Roche. The Company also expects to enroll its first patient in the fourth quarter of 2025 in a cohort evaluating RP2 in patients with biliary tract cancer. This cohort will evaluate RP2 combined with durvalumab."

P2 data • Trial status • Biliary Tract Cancer • Hepatocellular Cancer

RP2 and Tivozanib for the Treatment of Metastatic Renal Cell Cancer After Progression on Immunotherapy (clinicaltrials.gov) - P2 | N=35 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Study of RP2 in Combination With Second-line Therapy in Patients With Locally Advanced or Metastatic HCC (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Replimune Inc. | N=30 ➔ 60

Enrollment change • Biliary Cancer • Cholangiocarcinoma • Hepatocellular Cancer • Oncology • Solid Tumor