Oncorus, Inc. announced the publication of preclinical data in Nature Communications highlighting the potential of its synthetic viral RNA (vRNA)/lipid nanoparticle (LNP) platform as a novel approach to treating cancer by enabling repeat intravenous (IV) administration of viral immunotherapy. Data published demonstrate vRNA/LNP delivery and selective replication, virus assembly, spread and lysis of tumor cells, leading to potent anti-tumor efficacy even in the presence of virus neutralizing antibodies in the bloodstream. The article describes the design and development of Oncorus' synthetic RNA viruses for the systemic treatment of cancer.

The IV delivery of viral RNA genomes for two picornaviruses, Seneca Valley Virus (SVV) and Coxsackievirus A21 (CVA21), was formulated in LNPs. By encapsulating vRNA in LNPs, Oncorus was able to recapitulate oncolytic viral therapy in various tumor cells and avoid neutralizing antibodies. The vRNA/LNP constructs were well tolerated and elicited tumor-specific in situ production of oncolytic virions, immune cell recruitment and tumor destruction.

Efficacy was observed across multiple cancer models, including xenografts, PDX, GEMM and syngeneic models, with survival benefit observed in an orthotopic small cell lung cancer (SCLC) tumor model. Overall, synthetic RNA viruses were well tolerated after a single or multiple IV dose in mice and non-human primates. These results support the potential of this modality to expose all tumor lesions within a patient to a potently living drug that can both kill tumor cells and stimulate the immune system to fight cancer more effectively.

Oncorus has built a pioneering platform addressing significant unmet needs in cancer immunotherapy treatment. This novel IV-administered approach involves encapsulating the RNA genomes of viruses known to kill cancer cells in an LNP, resulting in a vRNA/LNP immunotherapy. Oncorus' LNP delivery strategy is intended to be less immunogenic than a natural viral capsid and is designed to overcome the challenges caused by neutralizing antibodies.

Using its platform, Oncorus has developed two vRNA/LNP immunotherapy programs, ONCR-021 and ONCR-788, which are based on CVA21 and SVV, respectively. The Company plans to submit an investigational new drug (IND) application with the U.S Food and Drug Administration (FDA) for ONCR-021 in mid-2023.