BriaCell

Overview

BriaCell Therapeutics (NASDAQ:BCTX, BCTXW;TSX:BCT) is a clinical-phase biotechnology company developing innovative immunotherapies for treating cancer.

With a recently awarded ‘fast track’ status from the FDA, BriaCell's lead candidate, Bria-IMT™, is immunotherapy currently being developed to treat advanced breast cancer. This type of cancer is expected to cause more than 43,000 deaths in the US in 2022. Bria-IMT™achieved positive proof of concept, showing outstanding safety and efficacy data. Importantly, preliminary efficacy data was similar, or superior to, those of other approved breast cancer drugs when they were at a similar stage of clinical development. After significant success, BriaCell received FDA fast track designation for this targeted immunotherapy approach.

BriaCell currently has a non-exclusive clinical trial collaboration with Incyte (NASDAQ:INCY) to evaluate the effects of combinations of novel clinical candidates. Under the agreement, Incyte and BriaCell will be evaluating novel combinations of compounds from Incyte's development portfolio with BriaCell's drug candidates in advanced breast cancer patients.

BriaCell has been dosing patients in Phase I/IIa combination study of BriaCell’s lead candidate, Bria-IMT™, with Incyte’s checkpoint inhibitor retifanlimab, provided under corporate collaboration with Incyte. The combination study is listed on ClinicalTrials.gov as NCT03328026.

BriaCell is also developing Bria-OTS™, an off-the-shelf personalized immunotherapy, for advanced breast cancer. Bria-OTS™ immunotherapy treatments are personalized to match the patient, without the need for personalized manufacturing. Bria-OTS™, which is expected to match over 99 percent of the patient population, is designed to produce a potent and selective immune response against the cancer while eliminating the time, expense and complex manufacturing logistics associated with other personalized immunotherapies.

In November 2020, BriaCell announced a cooperative research and development agreement with the National Cancer Institute (NCI, Center for Cancer Research), part of the National Institutes of Health, to investigate key aspects of novel off-the-shelf personalized therapeutics for cancer.

BriaCell's management team consists of experienced industry leaders who have been involved in the approval of more than a dozen drugs.

The Cancer Immunotherapy Space

There are a number of challenges that cancer immunotherapy treatments face. Approved immunotherapies work in 20 to 30 percent of patients. They depend on the patient's weakened immune system and, in some cases, can cause autoimmune disease.

Other challenges include the lack of effectiveness of cancer immunotherapies to treat some solid tumors or blood cancers, since they only work in certain types of cancer and not in others. Additionally, other effective personalized immunotherapies, such as PROVENGE® and CAR-T, need to be individually manufactured for each patient. This means a complex and time-consuming manufacturing process, which is extremely expensive, potentially making the therapies commercially unsuccessful.

In response to these challenges, BriaCell is developing Bria-OTS™, an off-the-shelf personalized immunotherapy, for advanced breast cancer, which is estimated to cause over 43,000 deaths in the US in 2022.

The off-the-shelf approach means that the treatments are pre-manufactured and the patient will be able to receive personalized, targeted treatment using an easy and common human leukocyte antigen (HLA) test on their saliva sample. This approach is quick, relatively inexpensive, and avoids the complex manufacturing process associated with other personalized immunotherapy treatments. This approach is the first of its kind for advanced breast cancer.

Bria-IMT™

Bria-IMT™, BriaCell'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. BriaCell believes that Bria-IMT™ helps the body to stimulate cancer-fighting T-cells, cells that directly attack tumor cells, and B-cells that produce anti-tumor antibodies.

Proof-of-concept clinical trials

The first clinical trial used the original unmodified breast cancer cell line, with low-dose cyclophosphamide and GM-CSF to boost the immune response. Fourteen patients were treated and produced impressive results, including no severe drug-related side-effects and a median survival rate in patients after treatment of about twice what was expected.

The second clinical trial used Bria-IMT™ (the original cell line – modified to produce GM-CSF, a stimulator of the immune system), along with low dose cyclophosphamide and interferon-alpha, in four advanced-stage cancer patients. The treatment was tolerated very well with few side effects. The median overall survival was much longer than expected. The study also had one patient that responded extremely well to the treatment, with an approximately 90 percent tumor reduction in breast cancer as well as the disappearance of cancer from the lungs and soft tissues.

After the treatment stopped, as required by the study, the patient's breast cancer returned and spread to the patient's brain, lungs and other sites. Importantly, the patient was treated again with Bria-IMT™ and the tumors were reduced at multiple sites, even in the brain. This patient-matched Bria-IMT™ for HLA genes which are used to match patients to tissues in tissue transplantation, such as for kidney transplants.

Phase I/IIa proof-of-concept study with Bria-IMT™: 2017 to 2018

BriaCell completed a Phase IIa study of Bria-IMT™ in advanced breast cancer in 23 patients that were heavily pre-treated (listed in ClinicalTrials.gov as NCT03066947) and released their initial data in September 2018. Bria-IMT™ treatment was safe and well-tolerated, with several instances of tumor reduction observed in certain patients sharing a key biomarker (HLA match) with Bria-IMT™. Most importantly, initial efficacy data was similar or superior to those of other advanced or approved drugs for breast cancer when they were at a similar stage of clinical development. Based on the recent findings related to the mechanism of action of Bria-IMT™, and the potential to produce intensified anti-tumor activity when used in combination with certain drugs.

Immune checkpoint inhibitors include anti-PD-1 antibodies, such as pembrolizumab (KEYTRUDA®, manufactured by Merck & Co.). More recently, Incyte's retifanlimab, also an anti-PD-1 antibody, is designed to neutralize immune suppression in cancer patients. The significance of immune checkpoints has been recognized by the Nobel committee by awarding Dr. Tasuku Honjo and Dr. James Allison with the 2018 Nobel Prize in Physiology or Medicine.

BriaCell believes that Bria-IMT™ can exert additive or synergistic, tumor-directed effects with checkpoint inhibitors like KEYTRUDA®. Initial safety data for the combined approach shows that it is very safe and well-tolerated by patients. Early efficacy data for the first eleven advanced breast cancer patients dosed with Bria-IMT™, in combination with KEYTRUDA®, suggested strong additive or synergistic effects on tumor regression (shrinkage). This included complete resolution of an “eye-bulging” tumor in an advanced breast cancer patient who had failed many prior treatments.

BriaCell hypothesizes that checkpoint inhibitors act by “awakening" a component of the immune system, while Bria-IMT™ “puts the foot on the gas" of the immune system, which may lead to more powerful anti-tumor activity.

BriaCell also received a fast track status for Bria-IMT™ from the US Food and Drug Administration (FDA) and will be applied to patients with metastatic breast cancer. BriaCell is developing Bria-IMT™ in combination with immune checkpoint inhibitors in a clinical trial listed on ClinicalTrials.gov as NCT03328026 . BriaCell is currently enrolling and dosing advanced breast cancer patients in its Phase I/IIa combination study of Bria-IMT™ with Incyte's checkpoint inhibitor, retifanlimab, and its immunomodulator, epacadostat under corporate collaboration with Incyte.

BriaCell Therapeutics' Collaboration with Incyte Corporation

In April 2019, BriaCell and Incyte Corporation formed a non-exclusive clinical trial collaboration to evaluate the effects of combinations of novel clinical candidates. Under the agreement, Incyte and BriaCell will evaluate novel combinations of compounds from Incyte's development portfolio with Bria-IMT™ in advanced breast cancer patients. BriaCell is currently enrolling and dosing advanced breast cancer patients in its Phase I/IIa combination study of Bria-IMT™ with Incyte’s checkpoint inhibitor, retifanlimab, under a corporate collaboration with Incyte. The goal of the program is to remove cancer-induced suppression of the immune system — taking the “foot off the brakes" that cancer puts on the immune system and stimulating an immune response with the Bria-IMT™ — putting the “foot on the gas". This is expected to allow the immune system to attack cancer in a targeted way with the help of Bria-IMT™. Recently awarded fast track status by the US Food and Drug Administration (FDA), the combination study is listed in ClinicalTrials.gov as NCT03328026.

Bria-OTS™

BriaCell is using a simple saliva test that would allow for personalized pre-made treatment for each patient based on the presence of certain biomarkers (HLA type), contrasting non-responder and responder patients. BriaCell is characterizing the molecular fingerprint of the responder patients, identifying them through the saliva test.

The Bria-OTS™ treatment is based on genetically engineered, pre-manufactured immunotherapies – each containing a specific HLA type – which can be selectively administered to patients based on the patient's HLA type. BriaCell is developing 15 unique HLA types that will allow for the treatment of over 99 percent of advanced-staged breast cancer patients. This approach provides customized cancer immunotherapy for each individual patient, without requiring personalized manufacturing.

Company Highlights

• BriaCell is an immuno-oncology-focused biotechnology company developing targeted and effective approaches for the management of cancer.
• BriaCell has partnered with Waisman Biomanufacturing to manufacture and supply prostate cancer immunotherapy
• The company has entered a research agreement with Harvard Medical School in support of a project led by Joan S. Brugge to identify Novel targets for cancer treatment
• BriaCell secured an exclusive license from the University of Maryland, Baltimore County (UMBC) to develop and commercialize Soluble CD80 (sCD80) as a biologic agent for the treatment of cancer.
• BriaCell signed an agreement with Caris Life Sciences to develop immunotherapies that are personalized for each patient by expanding patient outreach and molecular profiling.
• BriaCell’s lead drug candidate Bria-IMT™ is targeting third-line advanced breast cancer with Phase I/IIa safety and efficacy showing similar or superior results to other advanced or approved drugs at a comparable stage
• The company plans to initiate a registration study on Bria-IMT™ combined with an immune checkpoint inhibitor during the first quarter of 2023.
• BriaCell’s clinical strategy team is involved in 19 drug approvals
• Bria-OTS™, is currently being manufactured at a cGMP facility and undergoing quality control testing for the potential upcoming clinical trial for patients with advanced breast cancer.
• BriaCell has received fast track status for Bria-IMT™ from the US Food and Drug Administration (FDA).