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Investor PresentationSpring 2021
The Future of Cancer Immunotherapy
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BriaCell Therapeutics Corp.Nasdaq: BCTX, BCTXW
TSXV: BCT
Forward-Looking Statements
BriaCell Therapeutics Corp. (“BriaCell”)
Except for historical information, this presentation contains forward-looking statements, whichreflect BriaCell’s current expectations regarding future events. These forward-looking statementsinvolve known and unknown risks and uncertainties that could cause BriaCell’s actual results todiffer materially from those statements. Those risks and uncertainties include, but are not limitedto, our ability to access capital, the successful and timely completion of clinical trials, the receipt ofall regulatory approvals and other risks detailed in our our registration statement on Form F‐1 whichwe filed with the Securities and Exchange Commission on February 21, 2020, as amended from timeto time and available at www.sec.gov. The forward-looking statements in this presentation are alsobased on a number of assumptions which may prove to be incorrect.
Forward-looking statements contained in this presentation represent views only as of the date ofthis presentation and are presented for the purpose of assisting potential investors in understandingBriaCell’s business, and may not be appropriate for other purposes. BriaCell does not undertake toupdate forward-looking statements, whether written or oral, that may be made from time to timeby or on its behalf, except as required under applicable securities legislation.
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Capitalization Structure
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Nasdaq: BCTX, BCTXWTSXV: BCT
Share Price (as of 3/18/21): US$3.88
Shares Outstanding: 5,624,313
Market Cap: US$22M
Common Shares issuable upon exercise of pre-funded warrants:
1,030,000
Options (US$36.58 WAEP): 18,052
Warrants (US$6.14 WAEP): 6,442,867
Cash (pro-forma for 2/26/21 $25M financing,
excluding underwriting discounts, commissions, and other offering expenses):
$25M
Website: www.BriaCell.com
Stock Symbols:
BriaCell Corporate Highlights
BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW; TSXV: BCT) is a clinical stage immunotherapy company developing treatments that boost the ability of the body’s own cancer-fighting cells to destroy cancerous tumors
Lead drug candidate Bria-IMT™ is targeting third-line advanced breast cancer (the cause of over 40,000 deaths per year in the U.S.) and its associated U.S. patient population of ~70,000 patients
35 patients dosed to-date show robust response Our Phase I/IIa safety & efficacy show similar or superior results to those of other advanced or approved drugs for breast cancer at similar clinical stages of development
Incyte Corporation (Nasdaq: INCY) Corporate collaboration and supply agreement
Non-exclusive clinical trial collaboration to evaluate the effects of combination therapies
Bria-IMT™ + immune checkpoint inhibitors (Phase I/IIa)
1. Bria-IMT™ + pembrolizumab (KEYTRUDA®); dosed 11 patients transitioned to Incyte combination2. Bria-IMT™ + Incyte’s selected compounds under corporate collaboration
Registration Study initiation expected early-2022 Bria-IMT™ combined with immune checkpoint inhibitor
Bria-OTS™ “Off-The-Shelf Personalized” immunotherapy based on patient’s HLA-type that would address ~140,000 third-line breast cancer patients (99% of all third-line patients)
R&D Agreement with the National Cancer Institute (part of NIH)
CEO Dr. William Williams has been involved in 11 drug approvals
4Advancing towards pivotal early 2022 registration study commencement
William V. Williams, MD, FACP, President & CEO, Director Former VP, Exploratory Development, Incyte Corporation Former VP, Experimental Medicine, GlaxoSmithKline Former Head, Rheumatology Research, University of Pennsylvania Extensive drug development experience
Charles Wiseman, MD, Co-Founder & Director Former Assistant Professor at The University of Texas MD Anderson
Cancer Center Former Director, Immunotherapy Lab, St. Vincent Medical Center Clinical Professor of Medicine (retired), Keck-USC School of Medicine Former Acting Chief of the Division of Oncology/Hematology at the
White Memorial Medical Center
Rebecca A. Taub, MD, Director Current: CMO & EVP, Director, Founder, Madrigal Pharmaceuticals Senior VP, VIA Pharmaceuticals VP of Research, Metabolic Diseases, Hoffmann-La Roche Company Executive Director, Bristol-Myers Squibb Executive Director, Dupont Pharmaceuticals Professor of Genetics and Medicine, University of Pennsylvania
BriaCell’s Expert Drug Development & Financial Team
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Jamieson Bondarenko, CFA, CMT, Chairman of the Board Previously Principal and Managing Director of the Equity Capital Markets group
of Eight Capital Previously several positions at Dundee Securities Ltd., including Managing
Director, Director, Vice President and Associate
Vaughn Embro-Pantalony, MBA, FCPA, FCMA, CDir, ACC, Director Current: Chair, Board of Directors, Soricimed Biopharma Inc. Board and Audit Committee Member, Microbix Biosystems Inc. VP, Finance & CFO, Teva Novopharm Limited VP, Finance & Administration, Bayer Healthcare Director, Finance and Administration & CFO, Zeneca Pharma Inc.
Martin Schmieg, CPA, Director Current: CEO, ClearIT, LLC CFO: Sirna Therapeutics, Inc., & Isolagen, Inc. CEO, Freedom-2, Inc. (now PharmaCyte, Inc.) Advisor, Caladrius Biosciences, Inc., Beckman Coulter Genomics, Calimmune,
Inc., Cryoport, Inc., Vetbiologics, a division of U.S. Stem Cell, Inc., Sapientia Pharmaceuticals, Inc., & Rokk3r Labs, LLC
CEO Dr. William Williams was involved in 11 drug approvals in his career
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*NICL = Novel Immunotherapy Cell Lines **PKCδi = Protein kinase C delta inhibitor §Each of these IND filings would require an additional ~$1M above the baseline budget
BriaCell Pipeline
Therapeutic Indication Preclinical Phase I Phase II Phase III Anticipated Milestones
Bria-IMT™ + Incyte Compounds
Advanced Breast Cancer (3rd+ line)
Further safety and efficacy data through 2021
Bria-OTS™ Breast Cancer IND filing 2021
NICL1* Prostate Cancer IND Filing 2022
NICL2*Non-Small Cell Lung Cancer
IND Filing 2022
NICL3* Melanoma IND Filing 2022
Bria-TILsRx™ Prostate Cancer IND Filing 2022§
Bria-TILsRx™ Epithelial and Glandular IND Filing 2022§
PKCδi** RAS Transformed Cancers Candidate Selection 2021
Phase I/II
BriaCell’s Patented Immunotherapy: Bria-IMT™
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Mechanism of Action: Specific Immune Activation directly stimulates cancer-fighting cells in advanced breast cancer
Bria-IMT™ (developed from a breast cancer cell line) is a patented (USPTO) immunotherapy approach that directly stimulates the body’s own cancer-fighting cells to attack and destroy breast cancer tumors.
We believe that Bria-IMT™:
1. Produces antigens (proteins made by breast cancer cells).
2. Further boosts the immune response through secretion of a protein called GM-CSF.
3. The antigens are ‘presented’ to CD4+ and CD8+ T-cells, cells known for tumor destruction.
4. Also directly stimulates cancer-fighting T-cells, further boosting the response.
Bria-IMT™
Antigens
GM-CSF
CD4+
CD8+Tumor Destruction
PatientsHLA
MatchDisease Control*
Disease Control in Immune
Responders**
N=6 ≥ 2 50% 75%
N=20 ≥ 1 25% 33%
N=7 0 29% 29%
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*Includes 1 PR and 7 SD**Immune response measured by delayed-type hypersensitivity.
Bria-IMT™ – Phase I/IIa Efficacy in Breast Cancer
HLA-Type Matching and Biological Activity (original patients + Phase I/IIa data)
Patient 01-002 – Two HLA Matches
Patient 01-002 was treated with the Bria-IMT™ regimen and had what we conclude was a robust response, specifically substantial tumor regression in 20 lung metastases that all either disappeared or shrunk to tiny scars.
Pre-Treatment Post-Treatment
HLA Matching Hypothesis: Tumor regression appears to be most pronounced in patients who match Bria-IMT™ at specific HLA-types & develop an immune response
4 patients treated by Dr. Wiseman in 2004-2005 (original patients), including one remarkable responder.
23 patients were dosed in 2017-2018 (Phase I/IIa), all very heavily pre-treated (with chemotherapy).
Safety & Efficacy Data: We believe the data was similar or superior to those of other advanced or approved drugs for breast cancer at similar clinical stages of development.
Mechanism of Action & Proof-of-Concept
Bria-IMT™ in Combination with Immune Checkpoint Inhibitors
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Why did we combine Bria-IMT™ with immune checkpoint inhibitors?
• BriaCell has observed PD-L1 expression on circulating cancer cells & cancer-associated cells in >90% of our patients
• Bria-IMT™ increases the immune response, while checkpoint inhibitors decrease immune suppression
• Bria-IMT™ appears to have exerted additive or synergistic tumor-directed effects with checkpoint inhibitors
• BriaCell’s hypothesis: 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
How Do Checkpoint Inhibitors Work?
• PD-L1 molecules block immune cells from attacking cancer cells
• Immune checkpoint inhibitors are designed to neutralize this immune suppression in cancer patients
BriaCell is currently dosing Bria-IMT™ with Incyte’s selected compounds under a corporate collaboration
Bria-IMT™ + Immune Checkpoint Inhibitor Combination Study Data
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Phase I/IIa Combination Study in Advanced Breast Cancer
Patients were treated with the combination of Bria-IMT™ and anti-PD-1 antibody KEYTRUDA®.
An excellent safety and tolerability profile on the first 11 patients was observed.
All 11 patients were very heavily pre-treated with a median of 5 prior systemic therapy regimens (such as chemotherapy).
Most had very weak immune systems, further emphasizing the importance of the positive results observed.
As BriaCell had been purchasing the KEYTRUDA® for the study from Merck without a supply agreement, the study was switched to evaluating combination therapy with Incyte drugs and the combination with KEYTRUDA® was discontinued.
Patient HLA Match Observations Notes
1 0
25% reduction in sum of diameters of target liver metastases (breast cancer tumors in the liver).
8 prior chemotherapy or biological therapy regimens with extensive tumor growth in her liver.
Not an HLA match with Bria-IMT™ suggesting that—in combination with KEYTRUDA®—tumor reduction may occur without a match.
5 2
70% reduction in sum of diameters of target adrenal metastasis and complete resolution of orbital (behind the eye) metastasis.
Failed 12 prior regimens with 16 agents (13 chemotherapy and 3 hormonal).
Match at HLA-C and HLA-DRB3 loci.
Rolled-over from Bria-IMT™ study
Remarkable Responder announced Sept. 2019
Did not roll over
Bria-IMT™ + Immune Checkpoint Inhibitor: Remarkable Responder
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Complete resolution of orbital tumor in a heavily pre-treated patient with 2 HLA matches and a grade II tumor supports remarkable activity of the Bria-IMT™ combination regimen, and it is
worth noting that checkpoint inhibitors have not proven effective as monotherapy in advanced breast cancer
Tumor behind the left eye causing proptosis completely resolves
Baseline Scans
Six months On Treatment Scans
Summary: Bria-IMT™ in Advanced Breast Cancer Trials
12Sources: 1- Wiseman CL, Kharazi A. The Open Breast Cancer Journal, 2010, 2, 4-11; 2- Lacher et al. Front. Immunol. 9:776; 3- Williams et al. San Antonio Breast Cancer Symposium (SABCS), December 2019
Proof-of-concept trial Phase I/IIa monotherapy Phase I/IIa combination w/Keytruda®1 2
Median survival was in line or above
expected survival for salvage therapies (6-
12 months)
One patient with 2 HLA matches to Bria-
IMT™ developed prompt objective
complete remission of a lung lesion on CT
scans and near-complete regression of
multiple breast lesions on MRI
All 3 patients with grade I/II tumors had
disease control (100%)
Patients with grade I or II tumors and those
able to generate a robust immune
response appear more likely to respond
regardless of HLA match, suggesting PD1
inhibitor can compensate for lack of HLA
match
Bria-IMT™’s data in monotherapy showed
significant disease control in patients with
increasing number of HLA matches
PD-L1 expression was seen on Cancer-
Associated Macrophage-Like Cells (CAMLs)
in 21/23 patients
PatientsHLA
match
*Disease
Control
**Disease Control in immune
responders
N=6 ≥2 50% 75%
N=20 ≥1 25% 33%
N=7 0 29% 29%
*Includes 1 PR and 7 SD
**Immune response measured by delayed-type hypersensitivity.
Note that this includes the 4 patients from the second trial
PatientsHLA
match
*Disease
Control
**Disease Control in immune
responders
N=5 ≥2 40% 100%
N=7 ≥1 43% 75%
N=4 0 25% 25%
*Includes 1 PR and 3 SD
**Immune response measured by delayed-type hypersensitivity.
Note that this includes the 4 patients from the monotherapy trial
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Bria-IMT™ shows significant disease control in immune responders with increasing numbers of HLA matches both in monotherapy and in combination with Keytruda®
POC trial (2004-2006)
Patients N=4 (stage IV)
Safety ProfileWell tolerated; no
severe AEs
Median Survival 35 months
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Summary: Bria-IMT™ in Advanced Breast Cancer Trials
Phase I/IIa monotherapy1&2
Patient characteristics
No HLA
matches
(n=7)
≥1 HLA
matches
(n=20)
≥2 HLA
matches (n=6)
Age 54 ± 15 60 ± 10 60 ± 15
Median Prior Systemic Regimens
7 (range 2-9) 4 (range 0-12) 5 (range 1-10)
% ER/PR + 67% 47% 80%
% Her2/neu + 14% 16% 0%
% Triple Negative 33% 37% 20%
Disease Control 2/7 (29%) 6/20 (30%) 4/6 (67%)
DTH Response 7/7 (100%) 14/20 (70%) 4/6 (67%)
Disease Control in DTH Responders
2/7 (29%) 6/14 (43%) 4/4 (100%)
% Grade I or II 2/7 (29%) 6/20 (30%) 3/6 (50%)
Disease Control in Grade I or II
2/2 (100%) 3/6 (50%) 3/3 (100%)
No HLA
matches
(n=4)
≥1 HLA
matches (n=7)
≥2 HLA
matches (n=5)
Age 61 ± 11 61 ± 9 60 ± 11
Median Prior Systemic Regimens
6 (range 2-10) 4 (range 1-14) 4 (range 1-14)
% ER/PR + 75% 67% 50%
% Her2/neu + 50% 50% 50%
% Triple Negative 0% 0% 0%
Disease Control 1/4 (25%) 3/8 (38%) 2/6 (33%)
DTH Response 4/4 (100%) 4/6 (67%) 2/4 (50%)
Disease Control in DTH Responders
1/4 (25%) 1/4 (25%) 1/2 (50%)
% Grade I or II 1/3 (33%) 2/6 (33%) 1/4 (25%)
Disease Control in Grade I or II
1/1 (100%) 2/2 (100%) 1/1 (100%)
Phase I/IIa combination with Keytruda®3
Patient characteristics
Sources: 1 - Lacher et al. Front. Immunol. 9:776; 2 - Williams et al. San Antonio Breast Cancer Symposium (SABCS), December 2019
Importantly, the latest trials have included patients with a diversity of HR/Her2 status who have failed multiple prior systemic regimens
Bria-IMT™ in Grade I/II Tumors
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We believe these findings identify a patient population with higher clinical benefit rates
Breast Cancer Grade Correlates with Response Bria-IMT™ is derived from a grade II (moderately differentiated) breast cancer.
Genes expressed by Bria-IMT™ match best with grade I/II-derived Breast Cancer Cell Lines
~40% of recurrent breast cancers are grade I/II
Cell Lines
B00
1
06-0
04
05-0
02
04-0
03
03-0
01
06-0
01
01-0
02
06-0
05
A00
2
-100
-75
-50
-25
0
25
50
75
100
All Lesions %Changes
Patient
%C
ha
ng
e in
Gre
ate
st
Dia
mete
rs
Monotherapy
Combination Therapy
Monotherapy StudyGrade I/II patients with immune responses had clinical benefit (5/7 = 71%)
Patients very heavily pre-treated, median of 7 prior regimens
Combination StudyGrade I/II patients with immune responses had clinical benefit (3/3 = 100%)
Patients very heavily pre-treated with 14-15 prior regimens
5 / 7
3 / 3
Grade I/II Patients% Change Lesions
Median Overall Survival of 12.5 months
Recent publication in 3rd line patients (Kazmi S et al Breast Cancer Res Treat. 2020 Aug 17) showed a median overall survival of 7.2 - 9.8 months
Introducing… Bria-OTS™
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Bria-OTS™: Off-The-Shelf Personalized ImmunotherapyConfirmation of “Matching Hypothesis” resulted in BriaCell’s “OTS” strategy
• Cooperative Research and Development Agreement with the National Cancer Institute, part of the National Institutes of Health
• We believe our treatment is most effective when the patient’s HLA-type matches the Bria-IMT™ HLA-type
• We are engineering 15 unique HLA types (molecules), collectively referred to as Bria-OTS™, allowing for what we believe will be matching and treatment of over 99% of patients with advanced breast cancer
• Bria-OTS™ involves a simple saliva test to determine the HLA-type of each patient• Each patient will then be treated with the appropriate pre-manufactured Bria-OTS™ formulation
• Similar cell lines in development for prostate cancer, lung cancer, and melanoma, as well as a pre-clinical Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (USA)
We anticipate each patient will be treated with a pre-manufactured formulation based on HLA-type
Saliva TestCell-Types Identified
Bria-OTS™ Formulation Determined
Patient Treatment
Timeline for Key Clinical Programs in Breast Cancer
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Clinical data to be submitted to key scientific meetings including AACR, ASCO, and the San Antonio Breast Cancer Meeting
Anticipated Milestones
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
Bria-IMT™ + Incyte Compounds – Pre‐Registration Study Data
Bria-OTS™ – Authorization by FDA; 1st Patient Dosed
Bria-OTS™ – Pre‐Registration Study Data
Registration Study – Bria-IMT™ + Checkpoint Inhibitor
Registration Study – Bria-OTS™ + Checkpoint Inhibitor
2021 2022 2023