On October 7, 2022 Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapies company focused on stimulating the immune system to transform outcomes for cancer patients, reported the publication of preclinical data in Nature Communications highlighting the potential of its viral RNA (vRNA)/lipid nanoparticle (LNP) platform as a novel approach to treating cancer by enabling repeat intravenous (IV) administration of viral immunotherapies (Press release, Oncorus, OCT 7, 2022, View Source [SID1234621828]). Data published today 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.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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, Coxsackievirus A21 (CVA21) and Seneca Valley Virus (SVV), were formulated in LNPs. By encapsulating vRNA in LNPs, Oncorus was able to cause reductions in tumor growth 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 made great strides in the development of viral RNA encapsulated within LNPs, and this publication is an important first step in realizing the potential of our platform as we progress this highly innovated approach into the clinic. We are focused on overcoming the neutralizing antibodies seen in previous studies involving the IV-administration of RNA-based oncolytic therapeutics which has likely limited their effectiveness today and believe that our data supports the ability our self-amplifying vRNA/LNP constructs to overcome these challenges," said Theodore (Ted) Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. "As demonstrated in animal models outlined here, we’ve established a way to simultaneously cause direct tumor cell killing in addition to broad immune stimulation in multiple tumors through an IV-administered self-amplifying RNA encapsulated within an LNP. We look forward to progressing our first candidate from this platform, ONCR-021, in patients with non-small cell lung cancer, renal cell carcinoma, melanoma and hepatocellular carcinoma. We plan to submit an IND with the U.S. FDA for this program in mid-2023," said Matthew Kennedy, Ph.D., Vice President of Research at Oncorus and the lead author on this paper.
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.