Oncolytics Biotech

Oncolytics Biotech Inc. is a Canadian company headquartered in Calgary, Alberta, that is developing an intravenously delivered immuno-oncolytic virus called pelareorep for the treatment of solid tumors and hematological malignancies. Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus that induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses.[1]

History

Oncolytics Biotech Inc. was founded in Calgary in 1998 in response to discoveries made on the oncolytic potential of reovirus made at the University of Calgary during the 1990s.[2][3] In June 2000, it began trading on the Toronto Stock Exchange (TSX). On October 5, 2001, it was listed on the Nasdaq.[4]

Since its inception, Oncolytics Biotech Inc. has worked to take REOLYSIN, its proprietary formulation of human reovirus, through the development and regulatory requirements necessary to develop it as a potential cancer therapeutic.

REOLYSIN

REOLYSIN (trademarked) is the trade name for a first-in-class, systemically administered, immuno-oncolytic virus. REOLYSIN was developed from preclinical research done at the University of Calgary[2][3] by Jim Strong and Matt Coffey, Oncolytics' president, chief executive officer and chief operating officer. REOLYSIN'S generic name is pelareorep.

Pelareorep is a proprietary formulation of human reovirus, which is naturally found in mammalian respiratory and bowel systems.[7] Most people have been exposed to reovirus by adulthood, but the infection does not typically produce symptoms.[8] Reovirus was noted to be a potential cancer therapeutic when early studies suggested it reproduces well in certain cancer cell lines.[9][10] It has since been shown to replicate specifically in cells that have an activated Ras pathway with very little effect in cells that do not have active Ras pathways.[11] Activating mutations of the Ras protein and upstream elements of the Ras protein may play a role in more than two thirds of all human cancers, including most metastatic disease, which suggests that Reolysin may be an effective therapeutic for many Ras-activated tumor types and potentially for some cell proliferative disorders.[12][13][14]

In both single-arm and randomized phase 2 clinical studies, Pelareorep, in combination with various chemotherapeutic agents, has shown a trend to improve overall survival (OS) in certain indications and patient populations, while having a limited impact on objective response rate (ORR) or progression-free survival (PFS), a therapeutic profile consistent with those observed with approved immunotherapies. Based on these observations, Oncolytics believes Pelareorep has multiple components to its mechanism of action (MOA):[15]

Direct tumor lysis – selective viral replication in permissive cancer cells leading to tumor cell lysis;

Innate immune response – viral replication resulting in a cascade of chemokines/cytokines causing natural killer (NK) cells to recognize and attack cancer cells; and

Adaptive immune response – antigen presenting cells (APCs) display tumor-associated antigens (TAA) and viral-associated antigens (VAA) to educate T-cells to recognize and destroy cancer cells.

Clinical Development

REOLYSIN has completed clinical trials in a variety of cancer types. The company's clinical development plan is based on drug combinations that can potentially boost each response of REOLYSIN's mechanism of action, with three development pathways: 1) chemo combinations (direct cell lysis) 2) immunotherapy combinations (adaptive immune response) and; 3) combination with (immunomodulators) IMiDs / targeted therapy (innate immune response).[25]

As part of REOLYSIN's registration pathway, Oncolytics, in partnership with CCTG, is conducting a phase 2 clinical trial in metastatic breast cancer patients receiving standard weekly paclitaxel therapy.[21] In March 2017, the company announced positive overall survival data from the open-label, randomized study where, in the intention-to-treat patient population, there was a statistically significant improvement in median overall survival from 10.4 months on the control arm to 17.4 months on the test arm.[26] In May 2017, Oncolytics announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for REOLYSIN for the treatment of metastatic breast cancer,[27] and in September 2017, the company announced a successful End-of-Phase 2 meeting with the FDA.[28]

Oncolytics is conducting its first study of REOLYSIN in combination with checkpoint inhibitors in an open-label phase 1b trial. The trial will assess the safety and dose-limiting toxicity of REOLYSIN in combination with pembrolizumab (KEYTRUDA) and chemotherapy in patients with advanced or metastatic pancreatic adenocarcinoma who have failed, or did not tolerate, first line treatment.[29]

On March 16, 2017, Oncolytics announced that cancer charity Myeloma UK launched MUK eleven, a phase 1b trial studying REOLYSIN in combination with Celgene Corporation's immunomodulatory drugs (IMiDs), Imnovid (pomalidomide) or Revlimid (lenalidomide), as a rescue treatment in relapsing myeloma patients.[20] The first patient was treated in September 2017.[30]

Oncolytics is conducting two phase 2 clinical trials studying REOLYSIN in pancreatic cancer: in collaboration with the University of Texas, Oncolytics is studying REOLYSIN in combination with gemcitabine (Gemzar) in patients with advanced pancreatic cancer,[23] and in collaboration with the NCI, Oncolytics is studying REOLYSIN in combination with carboplatin and paclitaxel as a first line treatment of patients with recurrent or metastatic pancreatic cancer.[22]

type	Public
traded as	tsx: ONC, nasdaq: ONCY
industry	Biopharmaceutical
foundation	1998 Calgary, Alberta, Canada
location city	Calgary, Alberta
key people	Matt Coffey - President, and Chief Executive Officer, Chief Operating Officer; Kirk Look - Chief Financial Officer; Andres A. Gutierrez - Chief Medical Officer; Andrew de Guttadauro, President, Oncolytics Biotech (U.S.) Inc.
products	REOLYSIN, a first-in-class intravenously delivered immuno-oncolytic virus (IOV) for the treatment of solid tumors and hematological malignancies.
location country	Canada
homepage	www.oncolyticsbiotech.com

History

REOLYSIN

Research and Development Collaborations

Clinical Development

External links

References