THANK YOU FOR SUBSCRIBING
Pharma Tech Outlook Weekly Brief
Be first to read the latest tech news, Industry Leader's Insights, and CIO interviews of medium and large enterprises exclusively from Pharma Tech Outlook
Allison Hagerman, VP, Product Development; Kirk Look, CFOOn the cusp of revolutionizing immuno-oncology, and advancing OV therapy, is Oncolytics Biotech. The company is developing an intravenously delivered immuno-oncolytic virus called “pelareorep” to treat solid tumors and haematological malignancies. Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus that uniquely induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses.
A Non-Toxic, Safe and Efficient Treatment of Breast Cancer
Tumors can grow due to the lack of an immune response to the cancer cell. Tumor cells evade an immune response through key receptors called “checkpoints” that tell the immune system ‘do not attack me.’ Approved immunotherapies, including checkpoint inhibitors, are designed to block this pathway, thereby enabling the immune system to recognize and kill the cancer. Depending on the tumor type, as few as 1 in 5 patients will respond to checkpoint blockade. Responses are limited when tumors do not have the critical elements required for checkpoint blockade to work, such as T-cells, an inflamed tumor, and expression of checkpoints. “We want to increase the number of responders to more than one in five, as well as expand the range of tumors eligible for checkpoint blockade treatment. As opposed to harmful cytotoxic agents or radiotherapy, we’re stimulating the patient’s own immune system to be the most effective way of eliminating the cancer,” explains Andrew de Guttadauro, Global Head of Business Development.
Pelareorep has demonstrated the ability to localize to both primary and metastatic tumors. Much like monoclonal antibodies, and other similar biologic therapies, pelareorep acts systemically and, therefore, can be delivered via simple, intravenous delivery (IV). Upon IV delivery, the virus escapes neutralization in part by binding to peripheral blood mononuclear cells (PBMCs). After binding to PBMCs, the virus is handed off to tumor targets. Once at the tumor, the virus promotes an inflammatory immune response which upregulates the expression of immune checkpoints and causes T and NK cells to infiltrate the tumor and attack the cancer cells. By priming the tumor in this manner, pelareorep can increase the percentage of patients who respond to checkpoint inhibitors and open up new indications where checkpoint blockade has been ineffective.
We want to increase the number of responders to more than one in five, as well as expand the range of tumors eligible for checkpoint blockade treatment. As opposed to harmful cytotoxic agents or radiotherapy, we’re stimulating the patient’s own immune system to be the most effective way of eliminating the cancer
“The virus is very good at labelling these cells as foreign so that our immune systems can eliminate these tumors and train the patient’s immune system to eliminate the disease from the body,” commented Dr. Matt Coffey, President and CEO of Oncolytics. Two essential safety features of pelareorep are its inability to replicate in non-cancer cells and to be actively cleared by the immune system. The virus can selectively replicate only in permissive cancer cells located in the primary tumor and metastatic sites in response to defective cell signalling pathways, a high level of genomic mutations, and cellular stress from chemo or radiation therapy.
Upon virus replication, cancer cells lyse/die and release new virus particles to infect nearby cancer cells. Also, the binding of pelareorep to PBMCs promotes immune cell activation, further facilitating an anti-cancer immune response by activating innate and adaptive immune systems, converting immune-unresponsive ‘cold tumors’ into immune-responsive ‘hot tumors.’ Following cancer cell death by the virus, tumor and viral antigens are taken up by antigen-presenting cells (APCs). The APCs in our bodies process and present antigens to T-cells, thus training the adaptive immune system to recognize and kill cancer cells.
Matt Coffey, President & CEO; Andrew de Guttadauro, Global Head of Business Development"The virus is very good at labelling these cells as foreign so that our immune systems can eliminate these tumors and train the patient’s immune system to eliminate the disease from the body"
Accelerating the Future of Cancer Treatment
According to the American Cancer Institute, in 2019, an estimated 268,600 new cases of invasive breast cancer were diagnosed among women with Luminal A - HR+/HER2- being the most common type of breast cancer. Approximately 1 in 8 women (13 percent) will be diagnosed with invasive breast cancer in their lifetime, and 1 in 39 women (3 percent) will die from breast cancer. Breast cancer survival rates vary greatly worldwide—the lower survival rates prevalent in less developed countries can be explained mainly by the lack of early detection programs, resulting in a high proportion of women presenting with late-stage disease, as well as by the lack of adequate diagnosis and treatment facilities. To positively impact the statistics and increase survival rates, Oncolytics is currently researching pelareorep’s efficacy with other immunotherapy combinations, including Bavencio®, Keytruda®, Opdivo®, and Tecentriq®. The firm is continually seeking collaboration and partnership opportunities, particularly with checkpoint inhibitors and other immuno-oncology drugs that will enable them to advance pelareorep in either the adjuvant or metastatic settings. Based on its Clinical Development Plan, Oncolytics has already forged partnerships and collaborations with several market leaders such as Pfizer, Roche, Bristol-Myers Squibb, and Merck KGaA. The firm has approximately 400 patents issued globally, including approximately 50 in the U.S. and 20 in Canada. With the planning of a phase 3 registrational trial expected in 2021, pelareorep is currently being manufactured at commercial scale under a commercial supply agreement with Merck Millipore Sigma. “We are expecting insights from multiple phase 2 studies over the next 12-18 months then completing the phase 3 trial with the opportunity to be a commercial company after that,” Kirk Look, CFO at Oncolytics, concludes.
Company
Oncolytics Biotech
Management
Allison Hagerman, VP, Product Development; Kirk Look, CFO and Matt Coffey, President & CEO; Andrew de Guttadauro, Global Head of Business Development
Description
Oncolytics Biotech Inc. is developing pelareorep, a safe and well-tolerated intravenously delivered immuno-oncolytic virus (IOV) that targets cancer through a unique mechanism of action with two components, selective tumor lysis and activation of the innate and adaptive immune systems, creating an inflamed phenotype to treat a variety of solid tumors and haematological malignancies. The virus is classified as Biosafety Level-2 and is relatively safe to handle in laboratory environments with accidental exposure causing only mild side effects with symptoms such as a common cold or the flu
SAN DIEGO and CALGARY - Oncolytics Biotech® Inc. announced the presentation of additional translational data from the AWARE-1 breast cancer window-of-opportunity study conducted in combination with SOLTI-Innovative Cancer Research at The San Antonio Breast Cancer Symposium (SABCS).
"Translational data presented from the AWARE-1 study at SABCS showed that pelareorep induced the expansion of tumor-infiltrating lymphocytes, or TILs, in matched tumor biopsy and peripheral blood samples of newly diagnosed breast cancer patients. In addition, sequencing of the T cell receptors (TCRs) showed a more prominent expansion of existing TIL clones in the blood. We consider these results to be positive and important because they build on additional translational results reported this fall at two other medical meetings, The Society for Immunotherapy of Cancer (SITC) and The European Society for Medical Oncology (ESMO), from the AWARE-1 and GOBLET studies respectively, and provide further support for pelareorep's unique immunologic mechanism of action," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics. "Taken together, these translational data affirm pelareorep's ability to enhance T cell infiltration into tumors and expand TILs in the peripheral blood, which have been correlated with tumor response. We intend to incorporate these learnings into the designs of our registrational studies in metastatic breast cancer and pancreatic cancer."
Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics, commented, "A review of the AWARE-1 study translational data presented at this year's SABCS and previous scientific conferences demonstrates that pelareorep treatment, especially in combination with atezolizumab, results in:
• an increase in CelTIL score, which correlates with improved clinical outcomes in breast cancer
• increased CD8+ T cell infiltration into tumors
• the generation and expansion of T cell clones, especially TILs
• the upregulation of tumor PD-L1 expression
These findings confirm that pelareorep remodels the tumor microenvironment and stimulates tumor-directed immune responses, effects we believe are driven by the introduction of pelareorep's double-stranded RNA into cancer cells."
Dr. Heineman concluded, "Results from multiple prior studies lead us to believe that pelareorep has the potential to fill very important treatment gaps for both breast and pancreatic cancer patients. The translational data reported this fall emphasize the importance of TIL clone expansion in pelareorep-treated patients and represents an important area for further exploration. We believe that analysis of TIL clone expansion could become a helpful precision tool to provide an early indication of treatment response and serve as a potential guide to patient care with pelareorep. We remain dedicated to expeditiously advancing the clinical development of pelareorep in support of our goal to provide cancer patients with improved treatment options."