Cancer Discovery

New Paper Highlights Role of Immune Stimulating Cells that Shrink Advanced Breast Cancer Tumors

The research team at BriaCell Therapeutics Corp., an immuno-oncology focused biotechnology company with a proprietary targeted immunotherapy technology, published a paper that sheds light on the potentially unique mechanism of action of BriaCell’s lead product candidate, Bria-IMT™, in the journal of Frontiers in Immunology, the 5th most cited journal in Immunology.

The paper titled, SV-BR-1-GM, a Clinically Effective GM-CSF-Secreting Breast Cancer Cell Line, Expresses an Immune Signature and Directly Activates CD4+ T Lymphocytes, focuses on the mechanism of action of Bria-IMT™, also referred to as SV-BR-1-GM, and may explain the impressive early clinical data on tumor shrinkage observed in some patients with metastatic breast cancer.

As summarized in the peer-reviewed publication, a body of evidence suggests immune-stimulating actions of SV-BR-1-GM which the paper’s authors believe are unique to Bria-IMT™ compared with other similar approaches. Bria-IMT™ (SV-BR-1-GM), the Company’s lead product candidate, is derived from a specific breast cancer cell line. It is genetically engineered to release granulocyte-macrophage colony-stimulating factor (GM-CSF), a substance that activates the immune system. Bria-IMT™ is thought to help the body recognize and kill tumor cells by activating both T cells that directly attack tumor cells, and, potentially, B cells that produce anti-tumor antibodies.

Specifically, Bria-IMT™ contains several factors, including HLA Class II molecules, molecules which typically are involved in starting an immune response. These molecules directly activate CD4+ “Helper” T cells, a key component of the immune system, which can produce a strong immune response against tumor cells resulting in tumor size reduction also known as clinical regression. Complete or even partial regressions are difficult to achieve in advanced breast cancer patients who have failed the standard of care. BriaCell has previously reported such responses in patients with metastatic breast cancer, not only in soft tissue and visceral areas, but even in the brain, a difficult site to treat.

“The publication of BriaCell’s findings in such a prestigious peer-reviewed journal further validates our hypothesis that Bria-IMT™’s unique mechanism of action may be associated with a substantial tumor reduction in patients who match HLA Class II molecules with Bria-IMT™,” stated Dr. Williams, BriaCell’s President & CEO and one of the paper’s multiple authors.

“The findings outlined in this publication are the cornerstones of our pipeline of cell-based cancer therapeutics, referred to as Bria-OTS™, our off-the-shelf personalized immunotherapy for advanced breast cancer. This strategy will allow us to match/cover over 90% of the patients with advanced breast cancer as we work tirelessly to improve patient outcomes in the fight with this deadly disease,” Dr. Williams noted.

Immunotherapy has come to the forefront in the fight against cancer because it uses the body’s own immune system in recognizing and selectively destroying cancer cells while leaving normal cells intact. In addition, immunotherapy is also considered to be a more potent approach than chemotherapy and has the potential to prevent cancer recurrence.

The results of two previous proof-of-concept clinical trials (one with the precursor cell line not genetically engineered to produce GM-CSF and one with Bria-IMT™) produced encouraging results in patients with advanced breast cancer. Most notably, one patient with breast cancer that had spread to other sites (metastatic cancer) responded to Bria-IMT™ with a substantial reduction in tumor size and volume at multiple sites, including in the breast, the lung, soft tissues, and even the brain. This patient matched Bria-IMT™ at an HLA Class II allele (HLA type) known as HLA-DRβ3.  The observation that Bria-IMT™ expresses HLA-DRβ3, and the matching observed, imply a unique mechanism of action for Bria-IMT™ as well as a potential method to select patients most likely to respond.

BriaCell is currently conducting a Phase I/IIa clinical trial of Bria-IMT™ in patients with advanced breast cancer.  In this trial, to date, Bria-IMT™ treatment has been safe with instances of tumor reduction observed. This trial is listed in ClinicalTrials.gov as NCT03066947. The trial is being conducted along with the co-development of BriaDX™, the Company’s companion diagnostic test, to be able to predict the patients who will likely benefit the most from Bria-IMT™ treatments. Additionally, the FDA approved a rollover combination study of Bria-IMT™ with pembrolizumab [Keytruda®; manufactured by Merck & Co., Inc.] or ipilimumab [Yervoy®; manufactured by Bristol-Myers Squibb Company]. This study permits patients who stop responding to the treatment with Bria-IMT™ in the ongoing Phase I/IIa trial to be continue Bria-IMT™ in combination with Keytruda® or [Yervoy®. The rollover trial is listed in ClinicalTrials.gov as NCT03328026.

BriaCell also had an abstract accepted for publication in the proceedings for the American Society of Clinical Oncology (ASCO) national meeting.  The abstract discusses the clinical data on 6 patients dosed with Bria-IMT™ in 2017. The abstract notes that 2 of 6 heavily pre-treated patients showed tumor regression.  An excellent safety profile was noted as well as additional support for our companion diagnostic, BriaDX™.  This abstract can be accessed at this link: http://abstracts.asco.org/214/AbstView_214_229215.html. For additional information on BriaCell, please visit our website: http://briacell.com.

Based on their observation of superior tumor shrinking responses in the patients who shared certain HLA types with Bria-IMT™, BriaCell is developing Bria-OTS™, an off-the-shelf personalized Immunotherapy, for advanced breast cancer.  Bria-OTS™ includes a set of cell lines, each being similar to Bria-IMT™, which are being engineered to express various pre-manufactured HLA types.

With only 15 different HLA alleles, Bria-OTS™ cell line combinations are expected to cover at least about 90% of the United States’ population with double HLA matches while over 99% will have at least a single match. BriaCell expects to use BriaDX™ to determine HLA types of patients (to identify HLA alleles), and subsequently select one or two Bria-OTS™ cell lines with matching alleles for administration to the patient. This should produce a potent and selective immune response against the cancer of each patient while eliminating the time, expense, and complex manufacturing logistics currently used for other personalized immunotherapies. In essence, Bria-OTS™ should provide a personalized treatment without the need for personalized manufacturing.

The Company is currently conducting a Phase IIa trial (NCT03066947) with Bria-IMT™, and a rollover trial (NCT03328026) with Bria-IMT™ in combination with other immunotherapies. For further information on the Phase IIa trials, please visit https://clinicaltrials.gov/ct2/show/NCT03066947.

For additional information on BriaCell, please visit our website: http://briacell.com.

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