SAN DIEGO--(BUSINESS WIRE)--IconOVir Bio, Inc. (IconOVir), a preclinical-stage biotechnology company pioneering the next generation of oncolytic virus (OV) therapy to improve the treatment of patients with cancer, today announced new preclinical data demonstrating proof-of-concept for a proprietary combination of two selectivity mutations, made to Adenovirus (Ad) proteins E1A and E4-ORF6/7, both of which are incorporated into its rationally designed OV product candidates. The data, which were generated by IconOVir’s partners at the Salk Institute for Biological Studies, were shared in an abstract (e14543) titled “Highly selective and potent p16-CDK-RB-E2F targeted oncolytic virus therapies,” which was included in the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting Proceedings, an online supplement to the Journal of Clinical Oncology.
“IconOVir was founded on the belief that OVs can be rationally engineered to deliver deeper, more durable benefit to patients,” said Mark McCamish, M.D., Ph.D., President and Chief Executive Officer of IconOVir. “Our proprietary platform enables rapid, iterative and combinatorial engineering, screening and optimization of next-generation OVs, enabling us to impart desirable attributes to novel viruses while still maintaining the qualities that make Ad an attractive OV backbone. In the case of ICVB-1042, we incorporate a series of mutations to optimize potency, selectivity and tumor tropism, and potentially enable both intratumoral and intravenous administration. The abstract shared at ASCO describes the first pair of mutations that we introduced into ICVB-1042, which improve tumor selectivity without impacting replicative efficiency or sacrificing lytic potency. We look forward to advancing ICVB-1042 into clinical studies in 2022, as we pursue our mission of curing cancer and restoring life to every patient, everywhere.”
In normal cells, the p16/RB tumor suppressor pathway regulates E2F transcription factors, which activate critical genes for DNA replication. However, in nearly all solid tumors, one or more mutations in the p16-CDK-RB-E2F pathway genes aberrantly activate E2F and are critical in driving uncontrolled tumor proliferation. While difficult to target with traditional therapeutic modalities, these tumor suppressor loss of function mutations represent ideal targets for driving durable anti-tumor responses.
Ad has evolved viral proteins, such as E1A, that bind to RB to activate E2F transcription of viral and cellular genes required for viral replication. On this basis, multiple first-generation Ad OV candidates have been engineered to contain RB binding domain mutations in the E1A gene in an effort to prevent E2F activation and replication in healthy cells. However, IconOVir’s partners at the Salk Institute have shown that another viral protein, E4-ORF6/7, activates E2F independently of E1A and drives virus replication in normal cells, even when the E1A gene has been mutated.
In the abstract published in the ASCO Annual Meetings Proceedings, the Salk Institute team describes data showing that combining E1A and E4-ORF6/7 mutations in an Ad OV yields an improved selectivity/efficacy profile over first-generation OVs engineered with E1A-RB mutations alone by conferring E2F-dependent tumor-selective replication without negatively impacting lytic potency in cancer cells. Furthermore, this high degree of tumor-selectivity is maintained when combined with additional mutations to enhance the lytic potency, tropism and systemic bioavailability of Ad OVs, as in IconOVir’s lead candidate, ICVB-1042.
“While OV-based therapies have delivered meaningful benefit to select patient populations, first-generation therapies are limited in their lytic potency, tumor selectivity, and systemic bioavailability, which has prevented the full realization of the modality’s potential,” said Clodagh O’Shea, Ph.D., Wicklow Chair and Professor of Molecular and Cell Biology at the Salk Institute and Scientific Founder and Chair of the Scientific Advisory Board of IconOVir. “The data announced today demonstrate proof-of-concept for our belief that rationally designed OVs can overcome these historical challenges, by introducing mutations that enable viruses to specifically replicate in tumor cells, while leaving healthy cells unharmed. I look forward to collaborating with the IconOVir team as they advance ICVB-1042, the first rationally engineered OV to incorporate the dual E1A and E4-ORF6/7 mutation, into clinical development next year.”
IconOVir’s lead product candidate, ICVB-1042, is derived from Ad, a common cold virus. In preclinical studies, ICVB-1042 has been shown to infect and kill a broad range of tumor cells, including head and neck, bladder, lung and breast, suggesting that it could have potential utility in a wide range of solid tumor indications. IconOVir is advancing ICVB-1042 through preclinical development, with plans to file an Investigational New Drug application with the U.S. Food and Drug Administration in the first half of 2022.
About IconOVir
IconOVir is a preclinical-stage biotechnology company pioneering the next generation of oncolytic virus therapy to improve the treatment of patients with cancer. IconOVir’s proprietary oncolytic virus platform is based on technology developed by scientific founder Clodagh O’Shea, Ph.D., of the Salk Institute. It is designed to address key limitations of first- and second-generation oncolytic viruses and provide a personalized therapy for cancer patients. For more information, please visit www.iconovir.com and follow IconOVir on LinkedIn.
