Clinical Investigators Focusing on benefits of Reolysin, Kyprolis Combination in Multiple Myeloma

Feb 1, 2020 | City of Hope, Multiple Myeloma, Oncolytics Biotech Inc., Winship Cancer Institute

Clinical Investigators Focusing on benefits of Reolysin, Kyprolis Combination in Multiple Myeloma

Oncolytics Biotech’s virus-based anti-cancer therapy Reolysin (pelareorep) has the attention of top researchers from Winship Cancer Center and City of Hope who are studying how combinations including pelareorep and Kyprolis (carfilzomib) offer benefits to multiple myeloma patients.

The Roth Capital Partners Sponsored Call

Investment bank Roth Capital Partners sponsored a call for the discussion featuring two key principal investigators including Craig Hofmeister, MD associate professor at the Winship Cancer Institute at Emory University School of Medicine, and Flavia Pichiorri, MD, associate professor, City of Hope and reported by Myeloma Research News.

The Background Evidence

These investigators are referring to preclinical studies (e.g., lab and animals) and a Phase I clinical trial studying the side effects and best dose of wild-type reovirus when combined with carfilzomib and dexamethasone in treating patients with multiple myeloma that has come back following treatment (relapsed) or does not respond to treatment (refractory). The study sponsor, National Cancer Institute (part of NIH), noted that drugs used in chemotherapy, such as dexamethasone and carfilzomib, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing or spreading. A virus called wild type reovirus may be able to kill cancer cells without damaging normal cells and seems to work best when given chemotherapy. Giving wild type reovirus with chemotherapy, the sponsors hypothesized may be a more effective treatment than chemotherapy alone. Hence this study involves carfilzomib (Kyprolis)Dexamethasone, a corticosteroid, and Pelareorep, a proprietary isolate of the unmodified human reovirus being developed as a systematically administered immune-oncological viral agent for the treatment of solid tumors and hematological malignancies. Pelareorep is an oncolytic virus, which means that it preferentially lyses cancer cells.

What is Reolysin?

Reolysin (pelareorep), a type of oncolytic virus under investigation for the treatment of myeloma and other cancers. The virus is used to cause the immune system to launch an immune response against the cancer cells, so their action against the cancer cells is increased. It is a proprietary isolate of the unmodified human reovirus developed as a systemically administered immune-oncological viral agent for the treatment of solid tumors and hematological malignancies.

By 2015, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to pelareorep for malignant glioma. By May 2017, the FDA granted Fast Track Designation for pelareorep in metastatic breast cancer. The developer, Oncolytics Biotech, has more than 415 patents for pelareorep issued globally, including more than 60 in America and 20 in Canada with numerous pending worldwide.

The hypothesis of recent study?

Clinical investigators Craig Hofmeister, Flavia Pichiorri, and others suspect that the combination of Reolysin (pelareorep) and Kyprolis (carfilzomib) offer benefits to multiple myeloma patients. As reported in the talk by Myeloma Research News, Amgen’s Kyprolis chemotherapy blocks proteasome activity—a protein complex that removes unneeded or damaged proteins, which leads to the toxic buildup of faulty proteins inside cells causing the death of cancer cells. Kyprolis augments Reolysin’s entry into, and infection of myeloma cells. This combination of activity boosts anti-tumor immune responses, including T-cell responses against Reolysin-infected cancer cells.

Supporting the hypothesis, Dr. Hofmeister noted recently “I think carfilzomib promotes (Reolysin) infection by suppressing the innate antiviral response and our data suggest that it does not get in the way of T-cell activation.” 

Additional Improvements with PD-1 Suppressor

Clinical investigator Hofmeister also discussed the potential benefits of adding a PD-1 suppressor such as Opdivo (nivolumab) from Bristol-Myers Squibb to the Reolysin, Kyprolis and dexamethasone combination to overall improve patient response to fight off cancers such as multiple myeloma. Recent preclinical studies revealed that when Reolysin is replicated in cancer cells that this increases PD-L1 levels—the interaction with PD-1 on the cell surface of T-cells stops their activation. Hence in preventing the interaction, nivolumab may increase immune response in the battle against cancer cells.

A clinical trial has been organized based on this emerging knowledge. The open-label Phase I study sponsored by Emory University, in collaboration with Bristol-Myers Squibb, Oncolytics Biotech, University of Utah and City of Hope Medical Center analyzes the combination of Reolysin, Kyprolis, dexamethasone, and Opdivo in up to 62 adult patients diagnosed with relapsed or refractory multiple myeloma. The study commenced in 2018, and the primary conclusion is targeted for October 2021. Multiple Myeloma News reported that the first patient was treated in January 2019, and the study is recruiting patients. Study contacts can be found here

The sponsor and collaborators seek to establish a maximum tolerated dose of Reolysin in the combination and to determine if the combination of Opdivo and Kyprolis leads to a different safety profile than two therapies used alone. The investigators also seek to better understand the relative roles of Reolysin’s immune-related and direct effects in myeloma cells.

Oncolytics Biotech Inc.

Based in Calgary, Canada, the company is working on developing an intravenously delivered immune-oncolytic virus called pelareorep for the treatment of solid tumors and hematological malignancies. Pelareorep is anon-pathogenic, proprietary isolate of the unmodified reovirus that induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses.

Founded in 1998 in response to discoveries made on the oncolytic potential of reovirus made at the University of Calgary during the 1990s, it went public in 2000 and trades on the Toronto Stock Exchange as well as listed on the NASDAQ

Business & Finance

Oncolytics Biotech is priced at $2.62 per share, with a market capitalization of just over $68 million. The company represents significant financial risk as it has accumulated losses of $18.6 million in 2014, $13.7 million in 2015, $15.1 million in 2016, $15.6 million in 2017, and $17 million in 2018. By the end of 2018, they only had $13.7 million in the bank.

Pipeline

Their lead product, pelareorep, is involved in a number of clinical trials involving combination drug scenarios. See the link. Pelareorep is currently in two Phase II clinical trials. They have at least a few years left to prove the value of this pipeline and thin on the cash. 

Biomarkers Development

The company is developing a biomarker blood test to identify patients most likely to benefit from pelareorep.

Risks

As analysts from Seeking Alpha recently summarized, the company represents a promising disruption to the immune-oncology space; its platform is taken seriously as evidenced by major biopharma partners, however investors cannot ignore certain risks including the precious line they walk with finances.

Lead Research/Investigator for Research Discussed

Craig Hofmesiter, MD associate professor at the Winship Cancer Institute at Emory University School of Medicine

Flavia Pichiorri, MD, associate professor, City of Hope

Call to Action: If you or a loved one has been diagnosed with multiple myeloma, consider checking into patient associations such as International Myeloma Foundation, and the Multiple Myeloma Research Foundation.

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