Wikipedia

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]

Oncolytics Biotech Inc.
Company typePublic
TSX: ONC, Nasdaq: ONCY
IndustryBiopharmaceutical
Founded1998 Calgary, Alberta, Canada
Headquarters
Calgary, Alberta
,
Canada
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.
ProductsREOLYSIN, a first-in-class intravenously delivered immuno-oncolytic virus (IOV) for the treatment of solid tumors and hematological malignancies.
Websitewww.oncolyticsbiotech.com

History

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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. In 2000, Oncolytics Biotech Inc. received permission to conduct its first phase I clinical trial, which was designed to test the safety of REOLYSIN in human patients. The positive results[5] of this first study led to the rapid and continuous expansion of Oncolytics’ clinical trial program, with phase 2 studies beginning in Canada in 2001, U.S. and subsequent cross-border studies beginning in 2002, and enrollment in a multi-site phase 3 trial beginning in 2010.[6] The company has conducted numerous clinical trials studying REOLYSIN in variety of cancers, including pancreatic, breast, head and neck, prostate, lung, colorectal, bladder and ovarian cancers.[citation needed]

The company was issued its first Canadian patent in August 2000, and currently holds more than 415 patents worldwide, including more than 60 U.S. and 20 Canadian patents, and more than 60 applications pending worldwide.[citation needed]

REOLYSIN

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REOLYSIN is 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 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, REOLYSIN, 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 REOLYSIN 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.

Research and Development Collaborations

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Oncolytics Biotech Inc. has collaborated with the National Cancer Institute (NCI),[16] the University of Leeds,[17] the Canadian Cancer Trials Group (CCTG) (formerly the National Cancer Institute of Canada Clinical Trials Group)[18] and the Cancer Therapy & Research Centre at the University of Texas Health Science Center in San Antonio,[19] among others, to conduct multiple clinical trials in the United States and United Kingdom. Oncolytics is currently collaborating with Myeloma UK and Celgene Corporation,[20] the CCTG,[21] the NCI[22] and the University of Texas.[23] In May 2018, Oncolytics Biotech collaborated with Merck & Northwestern University for the research on second-line pancreatic cancer.[24]

Clinical Development

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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 a 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]

References

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  1. ^ "What is Reolysin? | Oncolytics Biotech Inc". Oncolytics Biotech Inc. Archived from the original on 2017-10-26. Retrieved 2017-10-25.
  2. ^ a b Strong, JE; Tang, D; Lee, PW (1993). "Evidence that the epidermal growth factor receptor on host cells confers reovirus infection efficiency". Virology. 197 (1): 405–11. doi:10.1006/viro.1993.1602. PMID 8212574.
  3. ^ a b Coffey, MC; Strong, JE; Forsyth, PA; Lee, PW (1998). "Reovirus therapy of tumors with activated Ras pathway". Science. 282 (5392): 1332–4. Bibcode:1998Sci...282.1332C. doi:10.1126/science.282.5392.1332. PMID 9812900.
  4. ^ "Annual Report 12 April 2002". SEDAR. Canadian Securities Administrators. Retrieved 21 September 2019.
  5. ^ Thirukkumaran, CM; Nodwell, MJ; Hirasawa, K; Shi, ZQ; Diaz, R; Luider, J; Johnston, RN; Forsyth, PA; et al. (2010). "Oncolytic viral therapy for prostate cancer: efficacy of reovirus as a biological therapeutic". Cancer Research. 70 (6): 2435–44. doi:10.1158/0008-5472.CAN-09-2408. PMID 20215509.
  6. ^ "ONCOLYTICS BIOTECH INC. | Oncolytics Biotech(R) Inc. Announces Opening of Enrollment in Phase 3 Trial for REOLYSIN(R) in Head and Neck Cancers". Newswire.ca. 2011-06-20. Retrieved 2011-08-08.
  7. ^ Nirbert, M. L.; Schiff, L. A.; Fields, B. N. (1996). "Reoviruses and their Replication". In Fields, Bernard N.; Knipe, David Mahan; Howley, Peter M. (eds.). Fundamental Virology (3rd ed.). Philadelphia: Lippincott-Raven. ISBN 978-0-7817-0284-3.[page needed]
  8. ^ White, CL; Twigger, KR; Vidal, L; De Bono, JS; Coffey, M; Heinemann, L; Morgan, R; Merrick, A; et al. (2008). "Characterization of the adaptive and innate immune response to intravenous oncolytic reovirus (Dearing type 3) during a phase I clinical trial". Gene Therapy. 15 (12): 911–20. doi:10.1038/gt.2008.21. PMID 18323793.
  9. ^ Hashiro, G; Loh, PC; Yau, JT (1977). "The preferential cytotoxicity of reovirus for certain transformed cell lines". Archives of Virology. 54 (4): 307–15. doi:10.1007/BF01314776. PMID 562142. S2CID 36721884.
  10. ^ Duncan, MR; Stanish, SM; Cox, DC (1978). "Differential sensitivity of normal and transformed human cells to reovirus infection". Journal of Virology. 28 (2): 444–9. doi:10.1128/JVI.28.2.444-449.1978. PMC 354293. PMID 214572.
  11. ^ Strong, JE; Coffey, MC; Tang, D; Sabinin, P; Lee, PW (1998). "The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus". The EMBO Journal. 17 (12): 3351–62. doi:10.1093/emboj/17.12.3351. PMC 1170673. PMID 9628872.
  12. ^ Duursma, AM; Agami, R (2003). "Ras interference as cancer therapy". Seminars in Cancer Biology. 13 (4): 267–73. doi:10.1016/S1044-579X(03)00040-3. PMID 14563121.
  13. ^ Bos, JL (1989). "Ras oncogenes in human cancer: a review". Cancer Research. 49 (17): 4682–9. PMID 2547513.
  14. ^ Norman, KL; Lee, PW (2005). "Not all viruses are bad guys: the case for reovirus in cancer therapy". Drug Discovery Today. 10 (12): 847–55. doi:10.1016/S1359-6446(05)03483-5. PMID 15970267.
  15. ^ "Oncolytics Biotech Inc. Announces Registration Pathway and Clinical Development Plan – Oncolytics Biotech Inc". Oncolytics Biotech Inc. Retrieved 2017-10-25.
  16. ^ "ONCOLYTICS BIOTECH INC. | Oncolytics Biotech(R) Inc. Announces Randomized Phase II Ovarian Cancer Study to be Conducted by the Gynecologic Oncology Group and Sponsored by the National Cancer Institute". Newswire.ca. 2011-06-20. Retrieved 2011-08-08.
  17. ^ "Bulletin Board". Therapy. 6 (2): 191–197. 2009. doi:10.2217/14750708.6.2.191.
  18. ^ "Oncolytics Biotech Inc. Announces Completion of Enrollment in Randomized Phase II Colorectal Cancer Study – Oncolytics Biotech Inc". Oncolytics Biotech Inc. Retrieved 2017-10-25.
  19. ^ "ONCOLYTICS BIOTECH INC. | Cancer Therapy & Research Center at The University of Texas Health Science Center and Oncolytics Biotech(R) Inc. Announce Multi-Trial Clinical Research Collaboration". Newswire.ca. 2011-06-20. Retrieved 2011-08-08.
  20. ^ a b "Oncolytics Biotech Inc. Enters into First-in-Class Collaboration with Myeloma UK and Celgene Using REOLYSIN in Combination with Imnovid or Revlimid in Patients with Myeloma – Oncolytics Biotech Inc". Oncolytics Biotech Inc. Retrieved 2017-10-25.
  21. ^ a b "A Study of Reolysin For Patients With Advanced/Metastatic Breast Cancer - Full Text View - ClinicalTrials.gov". Retrieved 2017-10-25.
  22. ^ a b "Carboplatin and Paclitaxel With or Without Viral Therapy in Treating Patients With Recurrent or Metastatic Pancreatic Cancer - Full Text View - ClinicalTrials.gov". Retrieved 2017-10-25.
  23. ^ a b "A Study of REOLYSIN in Combination With Gemcitabine in Patients With Advanced Pancreatic Adenocarcinoma - Full Text View - ClinicalTrials.gov". Retrieved 2017-10-25.
  24. ^ "Oncolytics collaborates with Merck & Northwestern University to begin phase 2 study of Reolysin in combo with Keytruda to treat second line pancreatic cancer". www.pharmabiz.com. Retrieved 2018-05-31.
  25. ^ "Clinical Trials | Reolysin | Oncolytics Biotech Inc". Oncolytics Biotech Inc. Archived from the original on 2017-10-26. Retrieved 2017-10-25.
  26. ^ "Oncolytics Biotech Inc.'s REOLYSIN Provides Statistically Significant Improvement in Overall Survival in Canadian Cancer Trials Group Sponsored Randomized Phase 2 Study in Metastatic Breast Cancer – Oncolytics Biotech Inc". Oncolytics Biotech Inc. Retrieved 2017-10-25.
  27. ^ "Oncolytics Biotech Inc. Announces FDA Fast Track Designation for REOLYSIN in Metastatic Breast Cancer – Oncolytics Biotech Inc". Oncolytics Biotech Inc. Retrieved 2017-10-25.
  28. ^ "Oncolytics Biotech Announces Successful End-of-Phase 2 Meeting with FDA for REOLYSIN in Metastatic Breast Cancer – Oncolytics Biotech Inc". Oncolytics Biotech Inc. Retrieved 2017-10-25.
  29. ^ "Study of Pembrolizumab With REOLYSIN and Chemotherapy in Patients With Advanced Pancreatic Adenocarcinoma - Full Text View - ClinicalTrials.gov". Retrieved 2017-10-25.
  30. ^ "Oncolytics Biotech Announces First Patient Treated in MUK eleven Study – Oncolytics Biotech Inc". Oncolytics Biotech Inc. Retrieved 2017-10-25.
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