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Forward-Looking Statements
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Except for historical information, this presentation contains forward-looking statements, whichreflect BriaCell’s current expectations regarding future events. These forward-lookingstatements involve known and unknown risks and uncertainties that could cause BriaCell’sactual results to differ materially from those statements. Those risks and uncertainties include,but are not limited to, our ability to access capital, the successful and timely completion ofclinical trials, the receipt of all regulatory approvals and other risks detailed from time to timein our ongoing quarterly and annual filings. The forward-looking statements in this presentationare also based on a number of assumptions which may prove to be incorrect.
Forward-looking statements contained in this presentation represent views only as of the dateof this presentation and are presented for the purpose of assisting potential investors inunderstanding BriaCell’s business, and may not be appropriate for other purposes. BriaCelldoes not undertake to update forward-looking statements, whether written or oral, that maybe made from time to time by or on its behalf, except as required under applicable securitieslegislation.
Investors are cautioned not to rely on these forward-looking statements and are encouraged toread BriaCell’s continuous disclosure documents, including its financial statements which areavailable on SEDAR at www.sedar.com.
Leading Technology: Novel cancer immunotherapy
Right Timing: Initiating a Ph I/IIa clinical trial to validate the impressive safety and efficacy data of the two preliminary Ph I clinical trials
Unique Approach: Companion diagnostic co-development
Significant Market Potential: Multiple cancer indications. A multi-billion dollar target market.
Solid Management: Experts in immunotherapy, diagnostics, & corporate governance
Poised to Unlock Value: Significantly undervalued. Several short- and long-term milestones. Potential partnerships.
Investment Highlights
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BriaVax™(SV-BR-1-GM)
Breast cancer cell line Allogeneic whole-cell vaccine secreting GM-CSF (“GVAX”). Scalable production - grows as cancer cell line in RPMI + 10% FBS. Irradiation prior to injection to prevent replication. Used in combination with cyclophosphamide, and post-treatment with
interferon-α. Expected Result: Boosting the patient’s overall immune response to the
tumor cells.
Target Population
2nd line use for late stage breast cancer. Potential use for early stage cancers sharing antigen(s) of vaccine cells. Potential use for non-breast cancers sharing antigen(s) of vaccine cells. Maintenance therapy for duration of disease
Cancer Immunotherapy
Dr. C. L. Wiseman (left) helped pioneer chemotherapies before they
were considered a possibility. BriaVaxTM is a proprietary breast cancer cell vaccine
expressing GM-CSF
,
Impressive safety and efficacy data in a
preliminary Phase I clinical trial
Planning Phase I/IIa testing of BriaVaxTM as 2nd line treatment
for metastatic breast cancer.
BriaVaxTM Development Story
First Phase I:
Used unmodified cell line + GM-CSF + cyclophosphamide
N = 14 late stage, treatment-refractory breast cancer patients
No significant adverse events, well tolerated
Median Overall Survival = 12.1 months
Second Phase I:
Used GM-CSF-engineered cell line + cyclophosphamide + interferon-α
N = 4 late stage, treatment-refractory (3 breast cancer, and 1 ovarian cancer) patients
No significant adverse events, well tolerated
Median Overall Survival = 35 months
One robust responder with >90% regression during treatment, subsequent relapse (upon
halting treatment) responded to re-treatment
Clinical Data to-date
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Second Phase I (using BriaVaxTM)
1 out of 4 Subjects responded with substantial tumor regression
Clinical Data to-date
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baseline 3 re-inoculations
Lesion 1
baseline 3 re-inoculations
Lesion 2
baseline 3 re-inoculations
Lesion 3
Clinical Data to-date
Hypothetical Mechanism of Action
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Tumor regression in a patient was directly related to rising levels of CD40 Ligand (CD40L), a protein that is expressed on components of the immune system including activated T cells, B cells, platelets, monocytic cells,
natural killer (NK) cells, mast cells, and basophils.
CD40L is known as one of the strongest stimulants of the immune system
resulting in dendritic cell maturation, and rising serum levels of CD4+, CD8+, and NK cells, i.e., immune cells known for their anti-tumor activities.
Tumor Regression – Series-I
BaselineBefore Treatment
3 Vaccines6 Weeks Treatment
6 Vaccines20 Weeks Treatment
Tumor Re-Regression – Series-II
Relapsed3 Additional Vaccines
8 Weeks
4 months to restart of treatment
CD40L Levels During TreatmentSeries-I
CD40L Levels During Re-TreatmentSeries-II
Hypothetical Mechanism of Action
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Hypothetical Mechanism of Action: CTA Analysis
Cancer Testis Antigens (CTAs): A class of cancer tissue specific antigens
PRAME: The CTA expressed in some breast cancers. The PRAME is also expressed in BriaVax™.
BriaVax™ injection may activate the patient T cells by PRAME recognition to cause tumor destruction.
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BriaVax™
LUMINAL* STROMAL*BASAL*
ERBB3+ ALDH-
ERBB3+ ALDH+
ERBB3-ALDH-
Nonclonogenic
Normal Breast Cells
*Shehata et al. (2012). GEO DataSet GSE35399.**Lowe et al. (2015). GEO DataSet GSE56718.
HMEC**
CEP55PBK
PLAC1PRAME
Hypothetical Mechanism of Action: HLA Analysis
BriaVax™ caused a significant tumor shrinkage in one patient (Subject A002) - even at metastatic sites (Wiseman and Kharazi, Breast J 2006).
HLA analysis of BriaVax™ and peripheral blood lymphocytes from the 4 patients showed that the special responder (subject A002) had the same Major Histocompatibility Complexes (MHCs) class I (HLA-A) and class II (HLA-DRB3) alleles as BriaVax™. This double-match may explain BriaVax™ ‘s strong tumor destruction activities in that subject.
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Subject IDSurvival
(months)
Tumor
regressionHLA-A HLA-B HLA-DRB3
A001 40.7 No 02:01 24:02 13:02 41:01 03:01 -
A002 33.7 Yes 02:01 11:01 18:03 44:02 02:02 -
A003 35.6 No 02:01 03:01 07:02 13:02 Negative -
B001 7.0 No 11:01 - 35:01 40:01 Negative -
BriaVax N/A N/A 11:01 24:02 35:08 55:01 01:01 02:02
Hypothetical Mechanism of Action of BriaVaxTM
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BriaVax™ expresses several genes known for their roles in immune cells,
including HLA-A and HLA-DRB3.
BriaVax™ may do one or few of the following:
A. Directly act as antigen-presenting cells (APCs)
B. Cross-Presentation: Dendritic cells may take up degraded BriaVax™ and present BriaVax™ antigens on their own MHCs to the patients T cells
C. Cross-Dressing: Transfer BriaVax™ antigens displayed on MHCs/HLAs to dendritic cells
Discovery of Gene Signature of BriaVaxTM – Implications
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BriaCell discovered a pair of biomarkers (HLA alleles) present in the top-responder and BriaVaxTM but not in the 3 other clinical trial subjects
Implications:
i. It improves our understanding of how the vaccine works, thus improving the likelihood of clinical success, and may accelerate the clinical development of BriaVaxTM.
ii. We plan to develop diagnostic tests to identify the top-responder (the patients for which the vaccine would work best) subgroup of patients.
We plan to further validate our discovery using the patients data in the upcoming Phase I/IIa study
IND Cleared by FDA in Nov 2015:
Up to 24 stage-IV breast cancer patients
Primary objective: Safety & tumor response
Designed to amend the trial to evaluate:
• Extending the dosing schedule (not limited to 6 vaccine injections)
• Use in combination with other treatments
• Application to earlier stage, more favorable to breast cancer patients
• Application to other tumors
Phase I/II Open Label Clinical Trial
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BriaVax™
Accelerating the Clinical Development of BriaVaxTM
BriaDx™
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Companion diagnostics co-development
Molecular analysis of blood and potentially
tumor samples
Predict BriaVax™ responsiveness
Low development costs
Combination therapy to boost efficacy:
Allogeneic tumor cell line +
GM-CSF secretion +
Cyclophosphamide +
Interferon-α
FDA has allowed the testing of BriaVaxTM for other cancer indications
Targeting a multi-billion dollar market
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Cancer Type
Annual
Mortality (US)
Potential Market (in
Million $US)
at $100K/yr
Breast 40,890 $4,089
at $100K/yr
Cancer Type
Annual
Mortality (US)
Potential Market (in
Million $US)
at $100K/yr
Lung 158,080 $15,808
Ovary 14,240 $1,424
Prostate 26,120 $2,612
Bladder 16,390 $1,639
Pancreas 41,780 $4,178
Gastric 10,730 $1,073 Brain 16,050 $1,605
Total others (non breast) 324,280 $28,339
Total (breast & others) $32,428
Source: American Cancer Society Facts and Figures 2016
Upcoming Milestones
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Milestone Expected Timing
Completion of manufacturing of BriaVaxTM for Ph I/IIa trial 2H2016
Initiation of Ph I/IIa clinical trials of BriaVaxTM 2H2016
Filing for additional patents 1H2017
Interim Data for Ph I/IIa trial 2H2017
Presentation of clinical data at a major conference 2H2017
Draft protocols for additional Ph II/III trials as counseled by FDA 2H2017
Management Board
Rahoul Sharan, CA, CEO & Director
Chairman, Potash Ridge 30 yrs of finance & accounting experience Board of directors of Ansell Capital Corp, Parallel Resources, & Galaxy
Capital Corporation Partner, S&P Group - Led financings in excess of $100M Public Accountant, Coopers & Lybrand
Markus Lacher, PhD, Senior Director, R&D
Sr. Clinical Scientist, Cesca Therapeutics, Inc. Founder, T cell Therapeutics, Inc., an mmune-oncology company Author of 1st Sequencing of Nuclear DNA of 5 clinical-grade human
embryonic stem cell lines, published in Stem Cell Research
Saeid Babaei, PhD, MBA, Chairman
Entrepreneur. 20 yrs of biotech leadership roles CEO, AbCelex - Obtained funds from a top agri-tech/biotech VC VP, Bus. Development, Lorus Therapeutics - Out-licensing a Ph III
immuno-oncology program Dir. of Corp. Development, Northern Therapeutics- Led partnership
to United Therapeutics
Martin Schmieg, CPA, Director
35 yrs of biotech, med-tech, and pharma experience CFO: Sirna Therapeutics, Inc., & Isolagen, Inc. CEO, Freedom-2, Inc. (now PharmaCyte, Inc.) Advisor, Caladrius Biosciences, Inc., Beckman Coulter Genomics,
Calimmune, Inc., Cryoport, Inc., Vetbiologics, a division of U.S. Stem Cell, Inc., Sapientia Pharmaceuticals, Inc., & Rokk3r Labs, LLC
Management and Board
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Charles Wiseman, MD, Co-Founder & Director
Oncologist - 45 years experience, pioneered chemotherapies Director, Immunotherapy Lab, St. Vincent Medical Center Chief, Breast Cancer Basic Research Lab, Univ. of Texas MD
Anderson Hospital & Tumour Institute; Assist. Prof., Dept of Molecular Carcinogenesis & Virology, MD Anderson; Acting Chief, Div. of Oncology, White Memorial Medical Center, Los Angeles
Gadi Levin, CA, MBA, CFO
CFO of Labstyle Innovations Ltd VP of Finance for two Israeli investment houses in the fields of private
equity, hedge funds and real estate Financial Consultant, various firms Accountant, Arthur Andersen
Financials
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Data as of 7/11/2016
Ticker TSX: BCT.V
Other Listing OTCQB: BCTXF
Shares outstanding (in Millions) 91.30
Market Cap (in Million CAD$ ) 15.98
Recent Deal Values
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Date Partnership
Development stage
at the time of the
deal Deal size Terms10/20/2014 Ph I Up to $1.15 Bil
6/29/2015 Juno Therapeutics/Celgene Ph I/II Up to $1Bil
8/10/2015 Ph I/II Up to $725M
8/24/2015 BioMarin - Medivation Ph III Up to $570M
9/16/2015 Discovery/Preclinical Up to $1.745 Bil
10/15/2015 Ph I Up to $1.74 Bil $350M upfront payments
$1.39 Bil-development & regulatory milestones
Royalties in double digits
12/21/2015 Halozyme, Eli Lilly Preclinical Up to $800M $25M upfront. Milestone payments of up to $160M for each of
up to five collaboration targets valued at up to $800M-Mid-
single digit royalties.
6/28/2016 Xencor-Novartis Preclinical Up to $2.4 Bil $150M upfront payment, with clinical, regulatory and sales
milestones for two drug candidates.
Inovio Pharmaceuticals, Inc.
- MedImmune
NewLink Genetics -
Genentech
Xencor, Inc. - Amgen
Five Prime Therapeutics,
Inc. - Bristol-Myers Squibb
Company
Upfront payment of $150 M; Up to $1 Bil payments for certain
milestones ; Escalating double-digit royalties
Upfront payment of $27.5 M; Up to $700M-development &
commercial milestones; MedImmune pays all developmental
costs; Double digit tiered royalties
Upfront payment of $150 M; Celgene buys 9.14M shares of
Juno's stock at $93/share, & will have the right to buy more
equity in Juno in specified windows/market premiums; Both
share global costs & profits with 70%-Celgene & 30% -Juno
$410M to license the drug worldwide from BioMarin; $160M for
certain regulatory & sales-based milestones; Royalties in the
mid-single digits
$45M Upfront Payment; Up to $1.7 Bil in Clinical, Regulatory &
Sales Milestone Payments; Mid to high single-digit royalties for
certain candidates
Near-term Plans
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Working closely with Cancer Insight, a CRO specializing in cancer immunotherapy,to enroll the first 9 patients.
Analysis of blood samples from the first few patients in the upcoming Phase I/IIaclinical trial to further address the hypothesis that previously identifiedbiomarkers indeed correlates with clinical efficacy.
Follow up treatments with the patients (the treatment cycle may be extended insome patients).
Discussing combination studies with potential partners including big pharma
Summary
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Proprietary vaccine for 2nd line use for advanced breast cancer with potentialfor 1st line use.
Initiating Phase I/II a to further validate the impressive preliminary Phase I data:• survival was increased by up to 5X• rapid response rate with little side effects
Planning to co-develop companion diagnostics.
Potential use for other cancer indications. Targeting a multi-billion dollarmarket.
The management consists of leading experts in immuno-oncology, diagnostics,and corporate governance.
Currently undervalued compared to immuno-oncology peers. PartnershipPotentials for combination studies.