cancer Cancer Discovery

Early Evidence of Efficacy and Safety Seen in Novel Targeted Immunotherapy

An immune-oncology focused biotechnology company, BriaCell, has provided a clinical update on its lead immunotherapy drug for advanced breast cancer.

BriaCell provided further update on its ongoing clinical trial of Bria-IMT™ according to Protocol WRI-GEV-007 (listed in ClinicalTrials.gov as NCT03066947).  Six patients have received inoculations since the trial began in early 2017, with the observation that the regimen was well tolerated, had few side effects, and appears safe.   Imaging studies on the first fully evaluable patient in the trial showed a mixed response, including “a clear response in multiple bilateral pulmonary nodules,” although there was evidence of progressive disease at other sites.

BriaCell has now retained an independent radiologist to evaluate these images, Dr. Andrew Thierry of Beverly Hills Cancer Center.  He noted complete to near complete resolution of the multiple lung lesions following 3 months of treatment which was maintained at 6 months stating “no new nodules consistent with near complete to complete treatment response.Dr. Myron H. Jacobs, Director of Pulmonary Medicine, Christian Hospitals, St. Louis, MO, also reviewed the scans and concurs with Dr. Thierry’s interpretation.  In his opinion, it is extremely unlikely these images, with many nodules all regressing, could be explained clinically by anything other than breast cancer metastases, responding remarkably well to the experimental regimen.

The lung regressions are especially notable as this patient had previously received many different courses of chemotherapy with a total of 8 different agents. The response in this patient is also highly significant as she shares two HLA matches with Bria-IMT™, lending further support to our hypothesis that a heightened anti-tumor response can be elicited by Bria-IMT™ in patients with HLA matches. This supporting data clears the path to the development of Bria-OTS™, our novel approach to a highly personalized immunotherapy, but without the usually associated high costs.

BriaCell’s Scientific Founder, and several of BriaCell’s Scientific Advisory Board (SAB) members, have shared their excitement.  Dr. Charles Wiseman, Clinical Professor of Medicine, Keck-USC School of Medicine and BriaCell’s Scientific Founder, noted, “While caution is always wise, I am impressed that our first fully evaluable patient revealed prompt, total and persistent disappearance of the lesions, without significant side-effects.  Disappearance of advanced cancer, with an agent such as Bria-IMT™, in heavily pre-treated patients, occurring as soon as 3 months, is extremely unusual.”

Additionally, SAB member Dr. Douglas Faller, Professor of Medicine, Pediatrics, Biochemistry, Microbiology, Pathology and Laboratory Medicine and former Director of the Boston University School of Medicine Cancer Center, stated, “Patients who have undergone such extensive prior treatment are usually very difficult to treat.  We are very highly interested in the developmental prospects of personalized immunotherapy, Bria-OTS™, which is expected to cover over 90% of the advanced breast cancer patients.”

Moreover, Dr. Thomas Kieber-Emmons, Deputy Director of the Winthrop P. Rockefeller Cancer Institute of the University of Arkansas for Medical Sciences, said, “BriaCell expects to use these findings to identify patients who would be the most likely to respond to Bria-IMT™ using widely available tests such as HLA typing, and to further develop Bria-OTS™ as a potentially safe and efficacious way to treat advanced breast cancer, currently an unmet medical need.”

The WRI-GEV-007 study remains ongoing with 3 clinical sites currently open: Santa Rosa, CA; Everett, WA; and Plantation, FL.  This trial is listed in ClinicalTrials.gov as NCT03066947.

Manufacturing Update: Frozen formulation development work for Bria-IMT™, expected to translate also to Bria-OTS™, is nearing completion. This new formulation would allow advanced shipment and stockpiling of ready-to-inject product. A new master cell bank is being manufactured at KBI Biopharma, Inc. and is expected to be available for release testing within the next few weeks.

“We are very excited with our new findings supporting our data from the earlier clinical trials and look forward to the opportunity to potentially enhance the lives of cancer patients,” said Bill Williams, BriaCell’s President and CEO. “As the President & CEO and an avid shareholder, I understand the challenges involved in the development of novel therapies and appreciate the long-term support of our stockholders. We are excited with respect to the opportunity and look forward to further develop our innovative platform of therapies to enhance the lives of the cancer patients with few to no treatment options.”

BriaCell is an immuno-oncology focused biotechnology company developing a targeted and safe approach to the management of cancer. Immunotherapy has come to the forefront of the fight against cancer, harnessing the body’s own immune system in recognizing and selectively destroying cancer cells while sparing normal ones. Immunotherapy, in addition to generally being more targeted and less toxic than commonly used types of chemotherapy, is also thought to be a potent approach with the potential to prevent cancer recurrence.

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. We believe that Bria-IMT™ helps the body to recognize and kill tumor cells by activating T cells that attack the tumor and B cells that produce anti-tumor antibodies.

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 metastatic breast cancer responded to Bria-IMT™ with substantial reduction in tumor burden including breast, lung, soft tissue and brain metastases. The company is currently conducting a Phase I/IIa clinical trial for Bria-IMT™ in patients with advanced breast cancer.  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. The interim data for the first 10 patients is expected by the first quarter of 2018. Additionally, the FDA recently approved the roll-over combination study of Bria-IMT™ with pembrolizumab [Keytruda®; manufactured by Merck & Co., Inc.] or ipilimumab [Yervoy®; manufactured by Bristol-Myers Squibb Company] for patients previously treated with Bria-IMT™ in the Company’s ongoing Phase I/IIa clinical trial in advanced breast cancer. The roll-over trial is listed in ClinicalTrials.gov as NCT03328026.

BriaCell is also developing Bria-OTS™, an off-the-shelf personalized Immunotherapy.  Bria-OTS™ consists of 14 individually pre-manufactured genetic alleles. BriaCell’s BriaDX™ companion diagnostic reveals a patient’s specific HLA-types and the 2 best matching alleles are administered to the patient. BriaCell’s 14 alleles (8 Class I and 6 Class II) cover approximately 90% of the Breast Cancer population while eliminating the complex manufacturing logistics required for other personalized immunotherapies. Bria-OTS™ is a personalized therapy without the need for personalized manufacturing.

Yet another item in the BriaCell pipeline is a novel, selective protein kinase C delta (PKCδ) inhibitor. PKCδ inhibitors have shown activity in a number of pre-clinical models of RAS genes’ transformed cancers including breast, pancreatic, non-small cell lung cancer and neuroendocrine tumors (such as carcinoid tumors).