Reolysin (pelareorep) / Oncolytics, Adlai Nortye - LARVOL DELTA

Phase 2 randomized, controlled study of pelareorep combined with 5-fluorouracil/leucovorin/ irinotecan (FOLFIRI) + bevacizumab (bev) for the second-line treatment of RAS-mutated, microsatellite-stable (MSS) metastatic colorectal cancer (ESMO 2026) - No abstract available

Clinical • Metastases • P2 data • Colorectal Cancer • Oncology • Solid Tumor • RAS

Oncolytics Biotech Announces Positive Preclinical Results Combining Pelareorep with a Pan-RAS Inhibitor in Colorectal Cancer (GlobeNewswire) - "During the initial treatment period, when pelareorep was administered every other day, pelareorep, the pan-RAS inhibitor and the combination each reduced tumor growth compared to the control. The greatest tumor reductions were observed in the RAS inhibitor and combination groups, demonstrating that pelareorep activity was maintained in the presence of RAS inhibition without evidence of antagonism between the two therapies...Following the transition to less frequent weekly pelareorep dosing, the incremental activity associated with pelareorep became less evident....Oncolytics plans to expand its preclinical evaluation of pelareorep with RAS inhibitors across additional dosing schedules and RAS-driven tumor models. These studies will be designed to further characterize pelareorep’s contribution to the combination, including its potential impact on the depth and durability of tumor response and the development of resistance to RAS-targeted therapy."

Preclinical • Colorectal Cancer

Proteasome inhibition enhances oncolytic reovirus therapy in multiple myeloma independently of its direct cytotoxic effects. (PubMed, J Hematol Oncol) - P1 | "Although characterized as immunosuppressive drugs, PIs improved RV delivery to MM cells but also enhanced anti-MM efficacy through immune-mediated killing of myeloma cells, independently of their PI sensitivity. These results highlight a more generalizable use of PIs as therapeutic companions to support oncolytic-based therapies in cancers."

Journal • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

IRENE study: Phase 2 study of oncolytic virus pelareorep and PD-1 inhibitor retifanlimab in metastatic triple negative breast cancer (SABCS 2024) - P2 | "Five patients received prior treatment with checkpoint inhibitors - pembrolizumab or atezolizumab. One patient had a partial response. Tumor tissue, stool and blood samples collected during treatment will be assessed to understand the role of PD-L1 expression and gut microbiome, especially in the patient with response."

IO biomarker • Metastases • Oncolytic virus • P2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8

BRACELET-1 (PrE0113): Inducing an inflammatory phenotype in metastatic HR+/HER2- breast cancer with the oncolytic reovirus pelareorep in combination with paclitaxel and avelumab. (ASCO 2023) - P2 | "Six pts (12%) previously received everolimus, and 3 alpelisib. The addition of pelareorep to PTX is an active regimen with a high 6-month PFS rate worthy of further study. One third of patients discontinued either pelareorep or avelumab due to toxicity, highlighting the need for attentive supportive care. Survival data is maturing."

Combination therapy • IO biomarker • Metastases • Oncolytic virus • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immune Modulation • Oncology • Solid Tumor • HER-2 • PD-1 • PD-L1

Pelareorep primes the tumor for checkpoint inhibition therapy by activating the interferon-gamma signaling pathway and tumor inflammation signature in early breast cancer patients - results of the AWARE-1 trial (SABCS 2022) - "Methods Newly diagnosed HR+/HER2- early BC patients were enrolled into two cohorts: Cohort 1 (C1): pela + letrozole (n=10); and Cohort 2 (C2): pela + letrozole + atezolizumab (n=10). Conclusions These results demonstrate that treatment with pela alters the TME to induce and enhance anti-tumor immunity. This enhancement of anti-tumor immunity may potentiate the TME for CPI therapy."

Checkpoint inhibition • Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2 • HLA-E • IDO1 • IFNG • PD-L1 • STAT1

Oncolytics Biotech Aligns with FDA on Registrational Path for Second-Line RAS-Mutant MSS Colorectal Cancer (Yahoo Finance) - "The Company submitted a Type D meeting request to the FDA regarding the potential expansion of REO 033 into a pivotal study. Specifically, Oncolytics sought FDA feedback on the validity of the currently designed REO 033 (Part A) to support expansion of a pivotal Part B, and whether a Part B could support a potential accelerated approval pathway based on objective response rate and duration of response, with progression-free survival serving as the basis for full approval...The FDA also suggested that the Company hold an End-of-Phase meeting to reach final agreement on key elements of the registration program....Based on the FDA's written feedback, Oncolytics plans to minimize the time between the generation of supportive Part A data and initiation of Part B by launching Part B start-up aactivities as soon as positive interim Part A data are available."

Clinical protocol • FDA event • Trial status • Colorectal Cancer

Oncolytics Biotech Receives Fast Track Designation for Pelareorep in Second-Line and Later Anal Cancer (GlobeNewswire) - "The designation is supported by encouraging efficacy demonstrated in the Company’s GOBLET study evaluating pelareorep in combination with a checkpoint inhibitor in patients with advanced SCAC whose disease had progressed following prior therapy."

Fast track • Anal Squamous Cell Carcinoma

Oncolytic Viruses in Cancer Therapy: Mechanisms, Challenges, and Emerging Clinical Applications. (PubMed, Ann Pharm Fr) - "Several OVs, such as herpes simplex virus 1 (HSV-1), human adenovirus type 5 (HAdV-C5), mammalian orthoreovirus type 3 Dearing strain (T3D; pelareorep), and Vaccinia virus-derived platforms (e.g., JX-594/Pexa-Vec), have shown significant therapeutic efficacy. Among them, Talimogene laherparepvec (T-VEC) (a genetically engineered HSV-1) has been approved by the Food and Drug Administration for melanoma treatment...OVT offers a dual-action therapeutic approach and holds significant promise in the field of precision oncology. Continued innovation and clinical validation are essential for its widespread adoption in cancer care."

Journal • Review • Herpes Simplex • Melanoma • Oncology • Solid Tumor

Oncolytics Biotech Reports FDA Regulatory Milestone and Strong Clinical Progress in Randomized RAS-Mutant MSS Colorectal Cancer Trial (GlobeNewswire) - "The Company continues to make rapid operational progress in Part A of REO 033 (n=60 patients), with approximately half of the planned clinical sites activated by the end of July, and more than 20 patients have been pre-identified across participating centers. The remaining sites are expected to be activated by the end of August, positioning the study for accelerated enrollment during the second half of 2026....The Company also announced that it will hold a Type D meeting with the FDA in the first half of August 2026 to discuss the registrational design for REO 033 through the addition of Part B of the study."

FDA event • Trial status • Colorectal Cancer

Oncolytics Biotech…announced that the United States Patent and Trademark Office ('USPTO') has issued a new patent broadly protecting the Company's proprietary manufacturing process for pelareorep (GlobeNewswire) - "The newly issued patent covers key aspects of the methods used to manufacture pelareorep and is expected to provide intellectual property protection into 2044....The Company also announced that a previously filed method-of-use patent application directed at pelareorep’s use as an immunotherapy remains under review and, if issued, is expected to provide protection into the year 2046. In addition, Oncolytics plans to file further patent applications this year that are designed to expand and strengthen the pelareorep intellectual property estate across additional therapeutic applications, treatment settings, and combination approaches."

Patent • Solid Tumor

Oncolytics Biotech...announced initial data from a preclinical study evaluating pelareorep in combination with RAS inhibitor modalities in a solid tumor model, which demonstrate evidence of greater anti-tumor activity in combination than with the individual approaches alone. (Yahoo Finance) - "Based on these findings, the Company is planning additional studies in models of pancreatic ductal adenocarcinoma ('PDAC') and colorectal cancer ('CRC') designed to further evaluate the combinations’ effects on immune activation, tumor response durability, and time-to-resistance...Full results from the initial preclinical studies are expected to be presented in the fall or winter of 2026."

Preclinical • Colorectal Cancer • Pancreatic Ductal Adenocarcinoma

Operation oncolysis: Reoviruses in the theater of cancer war. (PubMed, Adv Cancer Res) - "The most clinically advanced candidate, Mammalian orthoreovirus Pelareorep (Reolysin), has demonstrated efficacy across multiple malignancies, including breast cancer, glioma, and pancreatic adenocarcinoma, with generally manageable safety profiles...Exploration of emerging orthoreoviruses with distinct biological properties also presents new opportunities for therapeutic innovation. Collectively, reoviruses represent a compelling platform at the forefront of precision oncolytic virotherapy, with translational potential hinging on the resolution of critical mechanistic and clinical challenges."

IO biomarker • Journal • Brain Cancer • Breast Cancer • Glioma • Immune Modulation • Immunology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Influence of pelareorep on mutant KRAS-specific blood TIL clonal expansion. (ASCO 2026) - P1, P1/2 | "These findings suggest that pelareorep immunotherapy, through the combined activation of TLR3 and infection of the tumor, induces innate and adaptive antiviral and anti-tumor-specific immune responses capable of controlling tumor growth."

IO biomarker • Breast Cancer • Infectious Disease • Pancreatic Cancer • Solid Tumor • CXCL13 • KRAS • TLR3 • TRB

Oncolytics Biotech to Present Data at ASCO 2026 Reinforcing Pelareorep’s Potential Across Gastrointestinal Tumors (GlobeNewswire) - "Translational analyses from the Phase 1/2 GOBLET study in advanced pancreatic cancer and the AWARE-1 window-of-opportunity study in early-stage breast cancer illustrate a multi‑step immune activation process following treatment with pelareorep. Results demonstrate that pelareorep induces an antiviral immune response within the tumor via double-stranded RNA signaling, leading to expansion of virus‑specific T cells and subsequent activation of tumor‑specific T cells associated with tumor regression...In pancreatic cancer, serial blood analyses demonstrated expansion of anti‑viral T cells by ELISPOT and clonal expansion of tumor‑specific T cells after one cycle of therapy..In serial breast tumor biopsies, gene expression profiling demonstrated significant increases in antiviral and immune gene expression, consistent with activation of toll‑like receptor 3 (TLR3), alongside induction of CXCL13, a chemokine linked to the formation of tertiary lymphoid structures (TLS)."

Retrospective data • Breast Cancer • Pancreatic Ductal Adenocarcinoma

Oncolytics Biotech Sponsored by MilliporeSigma: Harnessing Oncolytic Reovirus to Remodel Tumor Microenvironments Through TLR3 Activation (ASGCT 2026) - "Sponsored by Oncolytics Biotech Sponsored by MilliporeSigma This presentation describes how Pelareorep, a novel first-in-class oncolytic reovirus immunotherapy, remodels tumor microenvironments by activating TLR3.Explore MilliporeSigma's Viral Vector CDMO ServicesLearn More About Oncolytics BiotechDiscover Oncolytics Biotech's Pipeline"

Biomarker • Oncolytic virus • Tumor microenvironment • Oncology • TLR3

GOBLET: A Study in Advanced or Metastatic Gastrointestinal Cancers Exploring Treatment Combinations With Pelareorep and Atezolizumab (clinicaltrials.gov) - P1/2 | N=122 | Active, not recruiting | Sponsor: Oncolytics Biotech | Recruiting ➔ Active, not recruiting

Biomarker • Enrollment closed • Anal Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • PD-L1

Bortezomib and Pembrolizumab With or Without Pelareorep for the Treatment of Relapsed or Refractory Multiple Myeloma, AMBUSH Trial (clinicaltrials.gov) - P1/2 | N=10 | Active, not recruiting | Sponsor: University of Southern California | Trial primary completion date: Aug 2026 ➔ Dec 2026

Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Identification of reovirus reassortants with enhanced oncolytic activity in human fibrosarcoma cells. (PubMed, Virus Genes) - "However, most preclinical and clinical studies have relied on a single prototype strain (T3D; clinically formulated as pelareorep), leaving open the possibility that other variants may exhibit superior activity in rare cancers...Pharmacologic pathway interrogation indicated that virus-induced cytopathicity in this model was predominantly caspase-dependent, supporting apoptosis as the primary mode of cell death rather than necroptosis. Collectively, these findings demonstrate that reassortant reoviruses can markedly enhance oncolytic activity in fibrosarcoma cells relative to commonly used strains, motivating broader evaluation of genetically diverse reoviruses across additional sarcoma models and in combination regimens to optimize therapeutic potential."

Journal • Fibrosarcoma • Infectious Disease • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Oncolytics Biotech… announced new durability data in metastatic colorectal cancer (’mCRC’), demonstrating meaningful and sustained clinical benefit in patients with RAS-mutant, microsatellite-stable (’MSS’) disease (Oncolytics Press Release) - "Pelareorep-based combination therapy demonstrated a 19.5-month median duration of response in second-line ('2L') KRAS-mutant MSS mCRC patients in the REO 022 study, compared to historical benchmarks of approximately 4–6 months in this setting. Additional data from this study include an objective response rate of 33% for patients receiving pelareorep, bevacizumab, and FOLFIRI, tripling the 6-11% for the standard of care....Oncolytics is currently enrolling patients in its randomized Phase 2 study evaluating pelareorep in combination with FOLFIRI and bevacizumab in second-line RAS-mutant MSS mCRC....The Company is actively engaging with the...FDA to discuss a potential accelerated approval pathway based on response durability and time-to-event endpoints from this study."

FDA event • P1 data • Trial status • Colorectal Cancer

Oncolytics Aligns with FDA on Planned Pivotal Anal Cancer Study (GlobeNewswire) - "Company to leverage strong durability and survival data in second-line and later metastatic squamous cell anal carcinoma...The Company plans to incorporate FDA feedback into the final protocol, which is expected to be a single, randomized controlled trial for which accelerated approval and full approval could be applied at different points in time."

FDA event • New trial • Anal Squamous Cell Carcinoma

FOLFIRI and Bevacizumab With or Without Pelareorep for Second-Line Treatment of Metastatic RAS-Mutated, Microsatellite-Stable Colorectal Cancer (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Oncolytics Biotech | Not yet recruiting ➔ Recruiting

Enrollment open • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • MSI

Pelareorep combined with atezolizumab and chemotherapy shows immune conversion activity in advanced pancreatic cancer: Biomarker results of cohort 1 of the GOBLET trial (AACR 2026) - "Pelareorep combined with atezolizumab and gemcitabine/nab-paclitaxel demonstrated promising activity in 1L pancreatic cancer. A hot/cold immune signature detectable after 4 weeks may serve as an early stratification biomarker, supporting identification of patients likely to achieve durable benefit"

Biomarker • IO biomarker • Metastases • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9 • CD8 • CXCL11 • GZMB • IFNG

Imaging mass cytometry of pelareorep treated early breast cancer samples reveals developing tertiary lymphoid structures (AACR 2026) - "This analysis focuses on Cohort 2 (n = 8), consisting of HR+ HER2- patients who received pelareorep on days 1, 2, 8, 9; letrozole on days 1-21; and atezolizumab on day 3. Other interactions of note were between tumor - ATH, tumor - CTC, tumor - DC, CTC - ATH, and CTC - CTC interactions were significantly increased at surgery. This study is the first of its kind to identify and spatially validate the unique cell-cell interactions in the TiME of early breast cancer patients treated with the OV pelareorep as developing TLS's, highlighting coordinated TiME reorganization and novel cell-cell interaction dynamics associated with TLS formation."

IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

In Vivo Tracking Modalities for Oncolytic Reovirus: Principles, Clinical Applications, and Translational Integration. (PubMed, Mol Imaging Biol) - "Emerging strategies, including synthetic biology reporters, AI-driven image analysis, biosensors, and liquid biopsies, provide scalable, patient-specific tracking solutions. This integrative framework bridges preclinical insights with clinical translation, supporting optimized design, monitoring, and personalization of oncolytic reovirus therapy."

Journal • Preclinical • Review • Infectious Disease • Oncology