Briacell Therapeutics Corp · TSX:BCT
Briacell Therapeutics — 3rd Annual Biologics World Nordic 2020 Conference
31 slides from Briacell Therapeutics's conference presentation, Sep 30, 2020
Slide 1: The Future of Cancer Immunotherapy
The Future of Cancer Immunotherapy info@BriaCell.com BriaCell.com 1-888-485-6340 3rd Annual Biologics World Nordic 2020 Conference Presentation 1
Slide 2: Cancer Immunotherapy Space
Cancer Immunotherapy Space The Problems ▪ Checkpoint Inhibitors: KEYTRUDA® (anti-PD-1), YERVOY® (anti-CTLA-4) and others reduce the tumor’s ability to suppress immune system. They only work in 20%-30% of patients and can cause autoimmune disease. ▪ Therapeutic Cancer Vaccines: Have not been successf
Slide 3: Development of SV-BR-1 and SV-BR-1-GM (Bria-IMT)
Development of SV-BR-1 and SV-BR-1-GM (Bria-IMT™) Histological grade of breast cancer as assessed by the Nottingham Grading System. (a) A well-differentiated tumor (grade 1) that demonstrates high homology to the normal breast terminal duct lobular unit, tubule formation (>75%), a mild degree of nuc
Slide 4: Expresses Multiple Breast/Cancer related Antigens
Bria-IMT™ Expresses Multiple Breast/Cancer related Antigens ▪ SV-BR-1-GM expresses 10000 Overexpressed in Breast Cancer dozens of breast tissue and w/o IFN-g w/ IFN-g cancer-related antigens (by 1000 RNA-seq). Breast Cancer-Testis Antigens Tissue RNA Levels (TPM) ▪ This enhances the chance for 100 a
Slide 5: Immune Signature of Bria-IMT
Immune Signature of Bria-IMT™ ▪ Bria-IMT™ expresses at least 22 immunostimulatory genes Gene symbol Official full name/description Aliases ADA Adenosine deaminase ADGRE5 Adhesion G protein-coupled receptor E5 CD97, TM7LN1 B2M Beta-2-microglobulin IMD43 CAV1 Caveolin 1 BSCL3, CGL3, LCCNS, MSTP085, PP
Slide 6: Bria-IMT and Bria-OTS Mechanism of Action
Bria-IMT™ and Bria-OTS™ Mechanism of Action The Problems ▪ Therapeutic Cancer Vaccines: Have not been successful in solid tumors or blood cancers with the exception of personalized approaches. ▪ Personalized Immunotherapies: ➢ Provenge® is effective for prostate cancer and uses a prostate- specific
Slide 7: Bria-IMT & Bria-OTS Potential Mechanisms of Specific Immune Activation
Bria-IMT™ & Bria-OTS™ Potential Mechanisms of Specific Immune Activation in Advanced Breast Cancer 4. Bria-IMT/OTSTM directly stimulates cancer fighting CD4+ and CD8+ T cells (further boosts the response) 3. Breast cancer antigens are taken up by dendritic cells and 5. Bria-IMT/OTSTM “presented” to
Slide 8: Bria-IMT Phase IIa Monotherapy Trial Design
Bria-IMT™ Phase IIa Monotherapy Trial Design BriaCell performed a Baseline: Imaging, labs, clinical evaluation Study Completed: phase I/IIa study in Bria-IMT™ cycles 1,2,3 ▪ 30 Metastatic Breast Cancer patients with advanced (week 1,3,5) patients screened and 23 breast cancer using the dosed Bria-IM
Slide 9: Study WRI-GEV-007 – Monotherapy Patient Characteristics
Bria-IMT™ Study WRI-GEV-007 – Monotherapy Patient Characteristics Patient Characteristics No HLA Allele 1+ HLA Allele 2+ HLA Allele (23 total) Matches (n=6) Matches (n=17) Matches (n=5) Age 55 ± 14 60 ± 8 68 ± 7 Median Prior Systemic 5.5 (range 2-13) 4 (range 0-10) 3.5 (range 3-7) Regimens % ER/PR +
Slide 10: Study WRI-GEV-007 – Monotherapy Safety Data
Bria-IMT™ Study WRI-GEV-007 – Monotherapy Safety Data Adverse Events seen in 2 or More Patients ADVERSE EVENT TERM Occurrences Patients Serious Adverse Events Erythema 42 11 Serious Adverse Event Severity Relationship to Bria-IMT™ Induration 32 7 Pruritis 13 7 Fever Grade 1 Unrelated Abdominal pain
Slide 11: Delayed Type Hypersensitivity to Bria-IMT
Bria-IMT™ Delayed Type Hypersensitivity to Bria-IMT™ DTH Responses 01-002 Rationale: Delayed-type hypersensitivity (DTH) is a good 06-001 06-003 marker of cellular (T cell) immune responses. Briefly, for 06-002 each cycle, Bria-IMT™ was injected intra-dermally with 5 04-007 DTH x 106 irradiated cell
Slide 12: Treatment Enhances Immune Responsiveness
Bria-IMT™ Treatment Enhances Immune Responsiveness T cell responses to PRAME Average Responders Average Non-Responders (Negative Control Subtracted) (Negative Control Subtracted) (a cancer testis antigen) 2000 Positive Control 2000 and HER2/neu peptides Positive Control (ECD = extracellular Observed
Slide 13: Anti-SV-BR-1 Antibodies in Patients
Anti-SV-BR-1 Antibodies in Patients 1:3 200 1:3 200 250 1:3 250 1:3 200 200 1:3 400 1:3 1:3 1:25 SV-BR-1 IgG Levels SV-BR-1 IgG Levels SV-BR-1 IgG Levels SV-BR-1 IgG Levels SV-BR-1 IgG Levels 1:25 1:25 SV-BR-1 IgG Levels 1:25 1:25 1:25 SV-BR-1 IgG Levels 200 200 1:25 150 150 % Change in % Change in
Slide 14: Study WRI-GEV-007 – Monotherapy Time on Study
Bria-IMT™ Study WRI-GEV-007 – Monotherapy Time on Study Time on Study Brown bars indicate patients unable to mount a 01-002 03-001 DTH response 04-005 05-002 02-003 Blue bars indicate patients able to mount a DTH 06-001 05-004 response 04-002 Patient Number 04-001 04-007 Arrows → indicate the patien
Slide 15: Bria-IMT Activity Dependent on Ability to Develop DTH
Bria-IMT™- Activity Dependent on Ability to Develop DTH Bria-IMT™ appears to be most effective in patients who match with Bria-IMT™ at HLA loci and who are able to mount a DTH response further supporting our “HLA Matching Hypothesis” HLA Matching and Biological Activity Disease Control** Disease Con
Slide 16: CTC & CAML PD-L1 expression
CTC & CAML PD-L1 expression • To date, >90% of patients analyzed have had PD-L1 expression on their CAMLs and CTCs • In Patient 01-002 (monotherapy study) CTCs and CAMLs were analyzed for PD-L1 Expression. • Mean levels increased from 97 ±7 to 437 ±72 (SEM). Representative Photos are Shown Below Con
Slide 17: Anti-PD-1 & Anti-PD-L1 Ineffective as Monotherapy in Breast Cancer
Anti-PD-1 & Anti-PD-L1 Ineffective as Monotherapy in Breast Cancer ▪ Brahmer 2012: treated 4 patients with breast cancer (sub-type not specified) – 0 response rate ▪ Nanda 2016: treated 32 patients with triple negative breast cancer (TNBC) with KEYTRUDA®, data on 27, all PD-L1+ ➢ 18.50% response rat
Slide 18: Bria-IMT Phase I/IIa PD1i Combination Therapy Trial
Bria-IMT™ Phase I/IIa PD1i Combination Therapy Trial Baseline: Imaging, labs, clinical evaluation Currently Recruiting: Bria-IMT™ 1,2,3, 4 (week 1,4, 7, 10) ▪ Treatment in combination with KEYTRUDA® (Merck & Restage: Imaging, labs, clinical evaluation Co., Inc.) or INCMGA00012 Non-progressive respon
Slide 19: Bria-IMT + Pembrolizumab Combination Patient Characteristics
Bria-IMT™ Bria-IMT™ + Pembrolizumab Combination Patient Characteristics Patient Characteristics No HLA Allele 1+ HLA Allele 2+ HLA Allele All Patients (11 total) Matches (n=4) Matches (n=7) Matches (n=5) (n=11) Age 61 ± 11 62 ± 9 62 ± 12 62 ± 9 Median Prior Systemic 6 (range 2-10) 4 (range 1-14) 4 (
Slide 20: Delayed Type Hypersensitivity to Bria-IMT + PD1i
Delayed Type Hypersensitivity to Bria-IMT™ + PD1i 06-005 Rationale: Delayed-type hypersensitivity (DTH) is a good marker of cellular (T cell) immune responses. Candida 06-006 (positive control) or 1x106 irradiated Bria-IMT™ cells 06-001 were injected intra-dermally in the forearm (DTH) and 5x106 in
Slide 21: Pembrolizumab Combination Time on Study
Bria-IMT™ Pembrolizumab Combination Time on Study Time on Study Blue indicates roll-over subjects time on Study 1 06-005 Green indicates time on combination therapy 06-001 Arrows → indicate ongoing in the study 04-005 06-004 Results: To date treatment has been generally safe Patient Number 04-007 an
Slide 22: Bria-IMT Activity Dependent on Ability to Develop DTH
Bria-IMT™- Activity Dependent on Ability to Develop DTH Bria-IMT™ appears to be most effective in patients who match with Bria-IMT™ at HLA loci and who are able to mount a DTH response further supporting our “HLA Matching Hypothesis” HLA Matching and Biological Activity Disease Control* Disease Cont
Slide 23: PD-1i Combination Tumor Responses
Bria-IMT™ + PD-1i Combination Tumor Responses Target Lesion Best %Changes Spider Plot Target Lesions PD-1i Combination 100 100 %Change in Greatest Diameters 80 80 60 60 40 2+ HLA Matches 40 20 % Change 1 HLA Match 20 0 No HLA Matches 0 -20 -20 -40 -40 -60 -60 -80 -80 -100 -100 06-004 06-007 06-001 0
Slide 24: Immune Checkpoint Inhibitor: Remarkable Responder
Bria-IMT™ + Immune Checkpoint Inhibitor: Remarkable Responder Tumor behind the left eye causing proptosis completely resolves Six months Baseline On Treatment Scans Scans Complete resolution of orbital tumor in a heavily pre-treated patient with 2 HLA matches and a grade II tumor supports remarkable
Slide 25: Bria-IMT in Grade I/II Tumors
Bria-IMT™ in Grade I/II Tumors Breast Cancer by Stage of Differentiation ▪ Breast cancer is classified based on histology into Grade I, II, or III. Also the designations “Luminal A”, “Luminal B”, “HER2+”, “triple negative (including “claudin-low”)” are used, denoting increased aggressiveness in this
Slide 26: Breast Cancer Grade Correlates with Response
Bria-IMT™ in Grade I/II Tumors Breast Cancer Grade Correlates with Response ▪ The clinical benefit rate in our monotherapy studies for Grade I/II patients with immune responses was 5/7 (71%) ➢ Patients very heavily pre-treated, median of 5 prior systemic regimens ▪ In our combination therapy study w
Slide 27: Bria-IMT in Grade I/II Tumors: Tumor Responses
Bria-IMT™ in Grade I/II Tumors All Lesions %Changes Time on Study Tumor 100 shrinkage seen Extensive time %Change in Greatest Diameters Patient 06-005 in most 75 on study patients with Combination Therapy Patient 06-001 especially with Grade I/II 50 Monotherapy combination Patient 01-002 Tumors. the
Slide 28: Bria-OTS & BriaDX
Bria-OTS™ & BriaDX™ Personalized Off-the-Shelf Immunotherapy ▪ Bria-OTS™ cell lines are being developed to express both GM-CSF and interferon-α PLUS patient- specific matching HLA types ▪ Cell lines will be pre-manufactured which express HLA alleles covering/matching with >99% of the overall advance
Slide 29: Bria-OTS – Off-The-Shelf Personalized Approach
Bria-OTS™ – Off-The-Shelf Personalized Approach 15 Unique HLA Types for Tailored Immunotherapies A simple test determines the correct “off-the-shelf” immunotherapy to select HLA Class I Types HLA Class II Types 1. Saliva test reveals the patient’s Class I and Class II HLA Types. 2. The correct pre-m
Slide 30: Bria-IMT & Bria-OTS Summary
Bria-IMT™ & Bria-OTS™ Summary ▪ Bria-IMT™ is a breast cancer cell line with features of an antigen presenting cell genetically engineered to express GM-CSF ▪ The Bria-IMT™ regimen has been used by itself to treat 27 patients with advanced breast cancer ▪ In spite of being heavily pre-treated, diseas
Slide 31: Thank You
The Future of Cancer Immunotherapy info@BriaCell.com BriaCell.com 1-888-485-6340 Thank You 31
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