Oncolytics Biotech

Last updated
Oncolytics Biotech Inc.
Type Public
TSX:  ONC, Nasdaq:  ONCY
IndustryBiopharmaceutical
Founded1998 Calgary, Alberta, Canada
Headquarters
Calgary, Alberta
,
Canada
Key people
Matt Coffey Ph.D. - President, and Chief Executive Officer, Chief Operating Officer; Kirk Look, CA - Chief Financial Officer; Andres A. Gutierrez, M.D., Ph.D. - 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.
Website www.oncolyticsbiotech.com

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]

Contents

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. 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

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]

Research and Development Collaborations

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

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]

Related Research Articles

An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune system responses. Oncolytic viruses also have the ability to affect the tumor micro-environment in multiple ways.

Cixutumumab (IMC-A12) is a human monoclonal antibody for the treatment of solid tumors.

Tigatuzumab (CS-1008) is a monoclonal antibody for the treatment of cancer. As of October 2009, a clinical trial for the treatment of pancreatic cancer, Phase II trials for colorectal cancer, non-small cell lung cancer, and ovarian cancer have been completed.

<span class="mw-page-title-main">Panobinostat</span> Chemical compound

Panobinostat, sold under the brand name Farydak, is a medication used for the treatment of multiple myeloma. It is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor.

<span class="mw-page-title-main">Dactolisib</span> Chemical compound

Dactolisib is an imidazoquinoline derivative acting as a PI3K inhibitor. It also inhibits mTOR. It is being investigated as a possible cancer treatment.

Pelareorep is a proprietary isolate of the unmodified human reovirus being developed as a systemically administered immuno-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. Pelareorep also promotes an inflamed tumor phenotype through innate and adaptive immune responses. Preliminary clinical trials indicate that it may have anti-cancer effects across a variety of cancer types when administered alone and in combination with other cancer therapies.

JX-594 is an oncolytic virus is designed to target and destroy cancer cells. It is also known as Pexa-Vec, INN pexastimogene devacirepvec) and was constructed in Dr. Edmund Lattime's lab at Thomas Jefferson University, tested in clinical trials on melanoma patients, and licensed and further developed by SillaJen.

Demcizumab is a humanized monoclonal antibody which is used to treat patients with pancreatic cancer or non-small cell lung cancer. Demcizumab has completed phase 1 trials and is currently undergoing phase 2 trials. Demcizumab was developed by OncoMed Pharmaceuticals in collaboration with Celgene.

<span class="mw-page-title-main">Talimogene laherparepvec</span> Gene therapy medication

Talimogene laherparepvec, sold under the brand name Imlygic, is a biopharmaceutical medication used to treat melanoma that cannot be operated on; it is injected directly into a subset of lesions which generates a systemic immune response against the recipient's cancer. The final four year analysis from the pivotal phase 3 study upon which TVEC was approved by the FDA showed a 31.5% response rate with a 16.9% complete response (CR) rate. There was also a substantial and statistically significant survival benefit in patients with earlier metastatic disease and in patients who hadn't received prior systemic treatment for melanoma. The earlier stage group had a reduction in the risk of death of approximately 50% with one in four patients appearing to have met, or be close to be reaching, the medical definition of cure. Real world use of talimogene laherparepvec have shown response rates of up to 88.5% with CR rates of up to 61.5%.

Vantictumab is a human IgG2 monoclonal antibody designed for the treatment of cancer.

<span class="mw-page-title-main">Oncolytic herpes virus</span>

Many variants of herpes simplex virus have been considered for viral therapy of cancer; the early development of these was thoroughly reviewed in the journal Cancer Gene Therapy in 2002. This page describes the most notable variants—those tested in clinical trials: G207, HSV1716, NV1020 and Talimogene laherparepvec. These attenuated versions are constructed by deleting viral genes required for infecting or replicating inside normal cells but not cancer cells, such as ICP34.5, ICP6/UL39, and ICP47.

<span class="mw-page-title-main">Palbociclib</span> Medication for HR+ HER2− breast cancer

Palbociclib, sold under the brand name Ibrance among others, is a medication developed by Pfizer for the treatment of HR-positive and HER2-negative breast cancer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Palbociclib was the first CDK4/6 inhibitor to be approved as a cancer therapy.

<span class="mw-page-title-main">Sonidegib</span> Chemical compound

Sonidegib (INN), sold under the brand name Odomzo, is a medication used to treat cancer.

<span class="mw-page-title-main">Aldoxorubicin</span> Medication

Aldoxorubicin (INNO-206) is a tumor-targeted doxorubicin conjugate in development by CytRx. Specifically, it is the (6-maleimidocaproyl) hydrazone of doxorubicin. Essentially, this chemical name describes doxorubicin attached to an acid-sensitive linker.

<span class="mw-page-title-main">Binimetinib</span> Chemical compound

Binimetinib, also known as Mektovi and ARRY-162, is an anti-cancer small molecule that was developed by Array Biopharma to treat various cancers. Binimetinib is a selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway. Inappropriate activation of the pathway has been shown to occur in many cancers. In June 2018 it was approved by the FDA in combination with encorafenib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma.

GL-ONC1 is an investigational therapeutic product consisting of the clinical grade formulation of the laboratory strain GLV-1h68, an oncolytic virus developed by Genelux Corporation. GL-ONC1 is currently under evaluation in Phase I/II human clinical trials in the United States and Europe.

Viralytics Ltd is an Australian biotechnology company working in the field of oncolytic viruses, that is, viruses that preferentially infect and kill cancer cells. The company's oncolytic virus product, called Cavatak, is currently in clinical trials in metastatic melanoma and other cancers. The drug was granted Orphan Drug status in advanced melanoma in December 2005.

<span class="mw-page-title-main">Gedatolisib</span> Chemical compound

Gedatolisib (PF-05212384) is an experimental drug for treatment of cancer in development by Celcuity, Inc. The mechanism of action is accomplished by binding the different p110 catalytic subunit isoforms of PI3K and the kinase site of mTOR.

SillaJen, Inc. is a South Korea-based biotechnology company, with offices in Busan, Yangsan and Seoul, South Korea, and San Francisco, California.

Transgene S.A. is a French biotechnology company founded in 1979. It is based in Illkirch-Graffenstaden, near Strasbourg, and develops and manufactures immunotherapies for the treatment of cancer.

References

  1. ↑ "What is Reolysin? | Oncolytics Biotech Inc". Oncolytics Biotech Inc. Archived from the original on 2017-10-26. Retrieved 2017-10-25.
  2. 1 2 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. 1 2 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. 1 2 "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. 1 2 "A Study of Reolysin For Patients With Advanced/Metastatic Breast Cancer - Full Text View - ClinicalTrials.gov" . Retrieved 2017-10-25.
  22. 1 2 "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. 1 2 "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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.