お知らせ • Jan 22
Oncorus, Inc. Announces Publication of Preclinical Data Demonstrating Potent Systemic Antitumor Activity of its Clinical Stage Oncolytic Herpes Simplex Viral Immunotherapy Product Candidate ONCR-177
Oncorus, Inc. announced the recent publication of preclinical data supporting the clinical development of its lead oncolytic Herpes Simplex Virus (oHSV) clinical candidate, ONCR-177. In the paper, entitled, “ONCR-177, an Oncolytic HSV-1 Designed to Potently Activate Systemic Antitumor Immunity” (Haines, et al., 2020), published online in the journal Cancer Immunology Research, ONCR-177 demonstrated potent and durable antitumor activity in multiple immune-competent tumor models. The preclinical findings demonstrate that the activity of ONCR-177, an intratumorally administered viral immunotherapy engineered for systemic activity currently in a Phase 1 study, is driven by Oncorus’ unique combination of five complementary immunomodulatory transgene payloads in addition to its retention of ?34.5. A herpes simplex virus 1 (HSV-1) gene, ?34.5 allows the virus to replicate in the presence of host antiviral immune responses. ONCR-177’s safety strategies and their ability to enhance oHSV tolerability without impeding potency were previously characterized in a paper published by Oncorus in September 2020 in Molecular Therapy on ONCR-159, the unarmed version of ONCR-177, (Kennedy et al., 2020) titled, “Design of an Interferon-Resistant Oncolytic HSV-1 Incorporating Redundant Safety Modalities for Improved Tolerability.” Oncorus is conducting a Phase 1 study to evaluate the safety and tolerability of ONCR-177 as well as to evaluate preliminary antitumor activity in patients with solid tumors (NCT04348916) as a monotherapy and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) via a clinical trial collaboration and supply agreement signed with Merck in July 2020. Oncorus expects to report initial interim data from the monotherapy dose escalation part of this trial in the second half of 2021 with addition data readouts through the second half of 2022. In addition to ONCR-177, Oncorus plans to nominate a second intratumorally administered oHSV clinical candidate to specifically target cancers of the central nervous system, including glioblastoma multiforme, in the second half of 2021 (ONCR-GBM). In the first half of 2021, Oncorus plans to nominate intravenously administered Synthetic Coxsackievirus A21 and Synthetic Seneca Valley Virus clinical candidates from its Synthetic Virus Platform for difficult-to-inject tumors such as those of the lung. Highlights from Oncorus’ preclinical data described in these papers include: The murine version of ONCR-177 (mONCR-171) demonstrated durable complete tumor regressions and abscopal activity in four syngeneic tumor models: A20, MC38, CT26 and B16F10N1. Durable survival was achieved in both A20 and CT26 models versus the unarmed version of ONCR-177 (i.e., ONCR-159), specifically demonstrating the impact that ONCR-177’s arming strategy has in driving systemic activity in these in vivo models of cancer. Re-challenge experiments in long term responders to mONCR-171 demonstrated that tumor antigen-specific protective memory responses were achieved. The retention of a gene coding for ?34.5
demonstrated more robust replication in the presence of interferon-? versus viruses that do not contain this gene. Of note, ONCR-159, which also retains ?34.5
expression, demonstrated statistically significant improvement in an in vivo bi-lateral CT26 model of survival. The addition of systemic anti-PD-1 augmented the activity of mONCR-171, particularly for un-injected tumors, suggesting that utilizing systemic anti-PD-1 immunotherapy may augment the systemic antitumor effect of ONCR-177. Directional viral promoters, CAG and MND, were shown to elicit strong transgene expression in injected tumors. Furthermore, the addition of the five complementary immunomodulatory transgenes and other modifications in ONCR-177 remain potently oncolytic in vitro in cancer cell lines. The oncolytic activity of ONCR-177 is on par with what has been reported for talimogene laherparepvec (IMLYGIC®), which is commonly referred to as “T-VEC”.1 In vivo biodistribution analyses suggest that viral DNA and transgene expression were relegated primarily to the injected tumor. As previously disclosed, no dose limiting toxicities were observed in the first four patients dosed with ONCR-177 suggesting that the safety strategies incorporated into ONCR-177 are working as intended.