Oncorus, Inc. announced the presentation of preclinical data for ONCR-719 in a poster at the 2022 Society for Neuro-Oncology (SNO) Annual Meeting, taking place November 17-20, 2022 in Tampa, Florida. ONCR-719 is a novel, armed oncolytic HSV-1 vector engineered with targeted entry via EGFR/EGFRvIII and expresses four immunomodulatory payloads designed to reverse GBM's immunosuppressive tumor microenvironment. In addition, ONCR-719 is derived from a potent HSV-1 isolate to drive oncolysis, is engineered with fusogenic mutations to enhance viral spread, and uses Oncorus' clinically validated microRNA attenuation strategy to inhibit viral replication in healthy cells.

Highlights from the preclinical poster describing ONCR-719, previously known as ONCR-GBM, include: Minimal expression of HSV-1 virus entry receptor, NECTIN-1, on human GBM samples suggests targeted oncolytic viruses are required to effectively treat human GBM tumors. ONCR-719 has been engineered to enter tumor cells using either EGFR/EGFRvIII or NECTIN-1 as an entry receptor, thereby increasing virus tropism for GBM tumors. EGFR-targeting and engineered fusogenic mutations in ONCR-719 enhance virus spread and tumor immunogenicity by driving syncytia formation in human GBM tumor cell lines.

ONCR-719 is engineered to include IL-12, an anti-PD-1 nanobody, 15-hydroxyprostaglandin dehydrogenase (HPGD), and a novel macrophage modulating-Fc enhanced antibody. These payloads confer enhanced T cell recruitment and activation and target the immune suppressive macrophages and myeloid cells in the tumor microenvironment. Multiple payloads or transgenes were screened using in vivo orthotopic GBM models to identify immune-modulatory payloads to target the GBM microenvironment.

Together, EGFR/EGFRvIII targeting, oncolytic potency, and incorporation of rationally designed payloads within ONCR-719 leads to enhanced anti-tumor efficacy and complete responses in preclinical orthotopic GBM models. ONCR-719 is engineered for safety in the central nervous system using multiple CNS-specific microRNA targets, Oncorus' clinically proven strategy to limit viral replication in healthy cells. When injected intracranially in an HSV-1 sensitive mouse, ONCR-719 demonstrates a greater than 50,000-fold tolerability window compared to the unattenuated strain.

ONCR-719 is the company's second candidate from its HSV Platform and is developed from a clinical isolate of HSV-1 selected for oncolytic potency across cancer cell lines. Further development of ONCR-719 is dependent on a strategic partnership or additional financing.