On April 1, 2019 Oncorus, Inc., an oncolytic virus therapeutics company focused on driving innovation to transform outcomes for cancer patients, reported preclinical data yesterday supporting the clinical advancement of its lead oncolytic virus candidate, ONCR-177, during an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 (Press release, Oncorus, APR 1, 2019, View Source [SID1234534841]). The data demonstrated that intra-tumoral administration of ONCR-177 resulted in high partial and complete response rates on both injected and non-injected tumors in preclinical models of several tumor types, including immune-inert, or cold, tumors. Responses were durable, resulting in an extension of survival and the establishment of protective immunity against tumor re-challenge.

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ONCR-177, a locally administered oncolytic virus therapy for the treatment of multiple solid tumor indications, is built on Oncorus’ proprietary, next-generation oncolytic herpes simplex virus (HSV) platform. ONCR-177 is armed with five transgenes, IL-12, CCL4, FLT3L, and CTLA-4 and PD-1 antagonists – representing the largest payload in the oncolytic virus therapy class – for potent stimulation of anti-tumor immunity. The therapy also employs an innovative microRNA (or miR)-attenuation strategy to enable selective viral replication in tumor cells, while preventing replication in healthy tissues.

"We are excited to share these important data driving the clinical advancement of ONCR-177," said Theodore (Ted) Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. "We are highly encouraged by the responses we’ve seen to treatment with ONCR-177 in multiple preclinical models as a result of the proprietary potency and safety innovations we have engineered. Our team continues to make remarkable progress on several fronts as we advance our best-in-class portfolio of oncolytic virus therapies for both local and systemic administration toward the clinic, with the goal of transforming outcomes for cancer patients."

Oncorus plans to file an investigational new drug application (IND) for ONCR-177 in 2019. In addition to its oncolytic HSV platform, Oncorus is also developing a novel synthetic oncolytic virus platform to enable the development of oncolytic virus therapies for repeated, systemic administration for uninjectable tumors, such as those of the lung.

About the Preclinical Findings

Intra-tumoral administration of the mouse surrogate of ONCR-177 in the oncolytic HSV-sensitive A20 BALB/c lymphoma bilateral tumor model resulted in response rates (partial and complete tumor regressions) of 100% and 80%, respectively, on the injected and uninjected tumor. mONCR-177 was also highly efficacious in the B16F10-nectin 1 melanoma model, an oncolytic HSV-resistant C57BL/6 based tumor model engineered to be permissive to oncolytic HSV by introduction of nectin-1, and in two colon carcinoma models CT26 and MC38.

mONCR-177 treatment resulted in increased numbers of activated NK cells, CD8+ and CD4+ effector T cells, and classical dendritic cells. The proportion of regulatory T cells, or Tregs, decreased, resulting in large increases CD8/Treg ratios. These changes in immune contexture occurred in both injected and uninjected tumors. They were more pronounced with mONCR-177 treatment compared to the base vector without payloads, indicating that the observed abscopal effects were due to mONCR-177’s elicitation of systemic anti-tumor immunity mediated in part by its payload of multiple transgenes.

"Due to their ability to kill cancer cells while eliciting a potent systemic antitumor immune response, ONCR-177 represents a potentially transformational treatment modality for cancer, as a monotherapy and in combination with checkpoint inhibitors," said Christophe Quéva, Ph.D., Oncorus’ Chief Scientific Officer. "At Oncorus, we have made important strides to overcome the ‘potency versus safety’ tradeoff that has historically held back this class of therapeutics, and we look forward to moving ONCR-177 into the clinic."

Oncorus has three additional poster presentations at the AACR (Free AACR Whitepaper) meeting showcasing the company’s proprietary potency and safety innovations for both its oncolytic HSV and synthetic oncolytic virus platforms, including:

Abstract #: 1455
Title: Design of ONCR-177 base vector, a next generation oncolytic herpes simplex virus type-1, optimized for robust oncolysis, transgene expression and tumor-selective replication
Session: PO.IM02.08 — Cancer Vaccines and Intra-tumoral Immunomodulation
Date and Time: Monday, April 1, 2019 / 8:00 am – 12:00 pm EDT
Location: Poster Section 22
Abstract Link: View Source!/6812/presentation/2749

Abstract #: 1452
Title: Development of ONCR-148, a miR-attenuated oncolytic HSV-1 designed to potently activate antitumor T cell response
Session: PO.IM02.08 — Cancer Vaccines and Intra-tumoral Immunomodulation
Date and Time: Monday, April 1, 2019 / 8:00 am – 12:00 pm EDT
Location: Poster Section 22
Abstract Link: View Source!/6812/presentation/2746

Abstract #: 4773
Title: Development of ONCR-NEP, a lipid nanoparticle delivered oncolytic virus capable of robust in situ amplification resulting in tumor lysis and regression
Session: PO.ET08.01 — Gene- and Vector-based Therapy
Date and Time: Wednesday, April 3, 2019 / 8:00 am – 12:00 pm EDT
Location: Poster Section 12
Abstract Link: View Source!/6812/presentation/1354