Oncorus Presents Preclinical Data Supporting ONCR-719, an armed HSV-1 Vector engineered to use the Epidermal Growth Factor Receptor (EGFR/EGFRvIII) for viral entry in Glioblastoma, at the 2022 Society for Neuro-Oncology Annual Meeting
- Category: DNA RNA and Cells
- Published on Friday, 18 November 2022 09:56
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- ONCR-719 is uniquely engineered to use the Epidermal Growth Factor Receptor (EGFR/EGFRvIII) for viral entry, which is highly expressed in glioblastoma multiforme (GBM); data show that the canonical entry receptor for HSV-1, NECTIN-1, is only minimally expressed in human GBM tumors.
- ONCR-719 expresses four immunomodulatory payloads, including IL-12, an anti-PD-1 nanobody, 15-hydroxyprostaglandin dehydrogenase (HPGD), and a novel macrophage-modulating Fc-enhanced antibody to reverse GBM’s immunosuppressed tumor microenvironment.
- ONCR-719 is derived from a potent HSV-1 strain that is engineered with fusogenic mutations to enhance viral spread and oncolysis and with Oncorus’ clinically validated microRNA attenuation strategy for safety.
ANDOVER, MA, USA I November 18, 2022 I Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapy company focused on driving innovation to transform outcomes for cancer patients, today 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.
“Oncolytic viruses are well-positioned to treat this aggressive form of brain cancer. We are excited to share ONCR-719 as a cutting-edge preclinical candidate that is engineered to improve outcomes and can stimulate a productive and durable anti-tumor immune response across multiple mouse models following a single intratumoral injection,” said Theodore (Ted) Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. “Most notably, we’ve enabled the virus to use EGFR for entry, which is expressed at high levels in GBM. Underscoring the importance of this advance is our data showing that the canonical entry receptor for HSV, NECTIN-1, is only minimally expressed in GBM cells, which arguably makes using EGFR for entry an essential capability for such an agent. By utilizing our clinically proven microRNA attenuation strategy, ONCR-719 is engineered to protect healthy brain tissue while replicating at its full potential in tumor cells.”
“GBM is the most common type of primary brain tumor in adults; it’s a devastating disease that has a great unmet need with a 5-year overall survival of approximately 7 percent,” said Tooba Cheema, Ph.D., Senior Director, Translational Medicine and ONCR-719 Program Leader at Oncorus. “We engineered ONCR-719 to overcome the common impediment that this treatment class faces, limited spread of virus in the highly immunosuppressive GBM tumor microenvironment. We are pleased with the results demonstrated in preclinical models and look forward to seeing how our innovations translate into improved outcomes for GBM patients.”
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.
At Oncorus, we are focused on driving innovation to deliver next-generation viral immunotherapies to stimulate the immune system and transform outcomes for cancer patients. We are advancing a portfolio of intratumorally (iTu) and intravenously (IV) administered viral immunotherapies for multiple indications with significant unmet need based on our Herpes Simplex Virus (HSV) and self-amplifying viral RNA/LNP Platforms.
Designed as a next-generation viral immunotherapy, our HSV Platform improves upon key characteristics of this therapeutic class to enhance systemic activity with immune stimulating payloads. Our lead HSV program, ONCR-177, currently in the clinic, is designed to be directly administered into a tumor, resulting in high local concentrations of therapeutic agent and its five encoded transgenes, as well as low systemic exposure to the therapy, which could limit systemic toxicities. Our pioneering self-amplifying vRNA/LNP Platform, highlighted by our product candidates ONCR-021 and ONCR-788, involves a highly innovative, novel combination of RNA and LNP-based modalities designed to realize the potential of RNA medicines for cancer. Please visit www.oncorus.com to learn more.