Defence Therapeutics Inc Class A · CSE:DTC
Defence Therapeutics Inc Class A — Investor Presentation (August 2022)
40 slides from Defence Therapeutics Inc Class A's investor presentation, August 2022
Slide 1: Making a Global Impact
Making a Global Impact | Defence Therapeutics Making A Global Impact Developing Unique Immuno- Oncology Solutions Slide Deck (August 2022) CSE: DTC FSE: DTC USOTC: DTCFF Confidentiel 1 Confidential
Slide 2: Defence Therapeutics corporate overview
Making a Global Impact | Defence Therapeutics Defence Therapeutics corporate overview Uniquely Positioned and Versatile Technology ● Defence Therapeutics is a Canadian Biotech developing next generation biopharmaceutical innovations for various immuno-oncology (IO) and infectious diseases (ID) indic
Slide 3: Board Members, Advisors and Management
Making a Global Impact | Defence Therapeutics Board Members, Advisors and Management Sebastien Plouffe, Director, President and CEO Michael Pfleiderer, Strategic Advisor MP Expert pharmaceutical advisor with focus on Financial expert and entrepreneur with 25+ years experience with public companies,
Slide 4: Current challenges: IO and ID
Making a Global Impact | Defence Therapeutics Current challenges: IO and ID Standard of care currently ineffective against disseminated cancers Targeted biopharmaceuticals struggle with molecular obstacles, limiting their potential to become a therapeutic standard for human diseases (i.e. cancer) No
Slide 5: Accum-Antigen X Technology
Making a Global Impact | Defence Therapeutics Technology eGFP-hGal3-Expressing DCs Accum molecule Bile acid NLS Antigen X • Proprietary platform technology with proven enhanced intracellular delivery • Promotes endosome-to-cytosol escape by 10 μm breaking down endosomal membrane • Various applicatio
Slide 6: Pipeline in Development
Making a Global Impact | Defence Therapeutics Pipeline in Development DISCOVERY PRE-CLINICAL PHASE I - 2023 Product INDICATION RESEARCH & DEVELOPMENT NON-GLP GLP Q2 Cell Vaccine ARM Melanoma Protein Vaccine AccuVAC-PT007 Cervical Cancer AccuTOX AccuTOX-001 Melanoma, Breast ADCs AccuADC-001 Breast CO
Slide 7: Introducing the A1-Reprogrammed Mesenchymal Stromal Cell (ARM) Vaccine Program
Making a Global Impact | Defence Therapeutics INTRODUCING THE A1-REPROGRAMMED MESENCHYMAL STROMNAL CELL (ARM) VACCINE PROGRAM: (Solid tumors: Melanoma) 7
Slide 8: Sipuleucel-T: The only FDA-approved DC cancer vaccine
Making a Global Impact | Defence Therapeutics Sipuleucel-T: The only FDA-approved DC cancer vaccine 8
Slide 9: Mesenchymal Stromal Cells (MSCs): A solution looking for a problem
Making a Global Impact | Defence Therapeutics Mesenchymal Stromal Cells (MSCs): A solution looking for a problem • Easily harvested • High yield, simple and cost- effective • Safety profile • Plasticity • Can be adapted to your problem! 9
Slide 10: Antigen Cross-Presentation Assay – OVA-linked Accum Variants
Making a Global Impact | Defence Therapeutics Antigen Cross-Presentation Assay 1 – OVA-linked Accum Variants 2 – OVA Admixed with Accum variants 10
Slide 11: Presentation Capabilities in Murine MSCs
11 Making a Global Impact | Defence Therapeutics OD Reading (570 nm) 0.0 0.5 1.0 1.5 MSCs SIINFEKL OVA Accum C-SV40-K-CA CA-NLS3 RPS17 CA-cMyc CA-NLS2 RSP17 CA-Tus CA-hnRNPD CA-NLS2-RQ CA-Nucleoplasmin CA-hnRNPM CA-NLS1 CA-PQBP1 CA-hnRNPA1 CDCA-NLS3 CDCAC-NLS1 RSP17 CDCA-SV40 DCA-SC40 GCDCA-PQBP1 GC
Slide 12: ARMs Exhibit Enhanced Antigen Uptake and Processing
Making a Global Impact | Defence Therapeutics ARMs ExHibit Enhanced Antigen Uptake and Processing OVA-AF647 OVA-DQ Uptake Processing A1 A1 + + + + - + - + + - + - - - - - OVA-AF647 OVA-DQ 12
Slide 13: The A1 Variant Triggers Endosomal Escape
Making a Global Impact | Defence Therapeutics The A1 Variant Triggers Endosomal Escape Accum rCytC A1 Adding Endosomal rCytC Entrapment - + + + - + - - + Live cells (no effect) - + - + - - Admixing Endosomal Apoptosis Dead - - - rCytC/A1 Escape Activation Cells Annexin-V 13
Slide 14: The A1 Variant Triggers ROS Via NADPH Oxidase (NOX)
Making a Global Impact | Defence Therapeutics The A1 Variant Triggers ROS Via NADPH Oxidase (NOX) ROS Detection A B Antigen Cross-Presentation C Antigen Cross-Presentation Fluorescent 200 200 2.5 2.5 1.2 1.2 ** Absorbance (570 nm) *** Mean Fluorescence * *** ** (570 nm) *** (MFI) 2.0 2.0 *** 150 ***
Slide 15: A1 Modules a Large Number of Genes and Triggers the Unfolded Protein Response
Making a Global Impact | Defence Therapeutics A1 Modules a Large Number of Genes and Triggers The Unfolded Protein Response Signatures Enriched in MSC + A1 + OVA (Up) 792 DEGs 814 DEGs 300 200 -Log10 P 100 0 -2 0 2 4 Log2 Fold Change NS 25 50 75 Log2 FC Gene Ratio p-value p-value and Log2 FC 15
Slide 16: Therapeutic Vaccination using Syngeneic ARMs Controls Lymphoma Growth
Making a Global Impact | Defence Therapeutics Therapeutic Vaccination using Syngeneic ARMs Controls Lymphoma Growth A B 5 x 105 Anti-PD-1 EG.7 EG.7 Tumor Days 0 7 14 21 28 35 42 5.0 x105 ARMs (SC) C D 100 Tumor volume (mm3) 1500 EG.7 EG.7 Percent survival 80 EG.7 + PD1 EG.7 + PD1 EG.7 + MSC 1000 EG.
Slide 17: Therapeutic Vaccination using Allogeneic ARMs Cures Established Lymphoma
Making a Global Impact | Defence Therapeutics Therapeutic Vaccination using Allogeneic ARMs Cures Established Lymphoma A B 5 x 105 Anti-PD-1 EG.7 EG.7 Tumor Days 0 7 14 21 28 35 42 5.0 x105 ARMs (SC) C Survival D of Survival_Allogeneic:Survival proportions 100 Tumor volume (mm3) 1200 MSC + OVA + EG.
Slide 18: Suggested A1 Mode of Action
Making a Global Impact | Defence Therapeutics Suggested A1 Mode of Action Protein Aggregation/UPR? 18
Slide 19: ARM Phase I/IIa trial (Canada): 3+3 Design
Making a Global Impact | Defence Therapeutics ARM Phase I/IIa trial (Canada): 3+3 Design (planned in Q2 2023) JGH-CPC (ARM Manufacturing) Part A Part B ARM Monotherapy Dosing ARM Escalation 3+3 Design + αPD-1 ARM Dose I ARM 10 x 106 Dose II ARM ARM Dose III JGH (Patients Treatment) 19
Slide 20: Introducing the Protein Vaccine Program: AccuVAC-PT007
Making a Global Impact | Defence Therapeutics INTRODUCING THE PROTEIN VACCINE PROGRAM: AccuVAC-PT007 (Solid Tumors: Cervical Cancer) 20
Slide 21: Current HPV vaccines are great, but not perfect!
Making a Global Impact | Defence Therapeutics Current HPV vaccines are great, but not perfect! - According to the CDC, the HPV vaccination decreased rates of infection with HPV in half in American teenagers (from 11.5% to 4.3%) and by one third in American women in their early twenties (from 18.5% t
Slide 22: Competitors in the Field
Making a Global Impact | Defence Therapeutics Competitors in the Field Prophylactic Vaccination Therapeutic Vaccination ➢ Gardasil VGX-3100 Cervarix (DNA Vaccine in Phase III) ➢ Gardasil 9 VS. AccuVAC-PT007 (E7 oncoprotein) 22
Slide 23: What Mechanism is Used by The HPV Virus to Trigger Cervical Cancer Development?
What Mechanism is Used by The HPV Virus to Making a Global Impact | Defence Therapeutics Trigger Cervical Cancer Development? Replication Capsid proteins Transcription Replication Oncogenes L1 E5 E2 E1 E7 L2 E4 E8 E6 Growth stimulation 23
Slide 24: AccuVAC-PT007 as a Prophylactic Vaccine Against Cervical Cancer
AccuVAC-PT007 as a Prophylactic Vaccine Against Making a Global Impact | Defence Therapeutics Cervical Cancer Rechallenges AccuVAC-PT007 0 1600 Ctl Ctl Tumor volume (mm3) 7 E7 1200 E7 Accum-E7 aE7 (AccuVAC-PT007) 14 800 400 21 C3.43 0 Challenge 28 0 16 32 48 64 80 96 Timeline (Days) 32 100 Percent s
Slide 25: AccuVAC-PT007 Can Be Also Used as a Therapeutic Vaccine Against Cervical Cancer
Making a Global Impact | Defence Therapeutics AccuVAC-PT007 Can Be Also Used as a Therapeutic Vaccine Against Cervical Cancer 100 Ctl Tumor volume (mm3) 1500 Percent survival 80 PD-1 CTLA4 1200 60 aE7 40 900 20 600 0 0 8 16 24 32 40 300 Timeline (Days) AccuVAC-P007 + ISA720 0 0 8 16 24 32 40 Days Ti
Slide 26: AccuVAC-P007 Phase I trial (Canada/USA): 3+3 Design
Making a Global Impact | Defence Therapeutics AccuVAC-P007 Phase I trial (Canada/USA): 3+3 Design (planned in Q1 2023) AccuVAC-PT007 Dose Escalation 3+3 Design Dose 1 AccuVAC-PT007 Still in discussion for the site Dose 2 AccuVAC-PT007 Dose 3 AccuVAC-PT007 26
Slide 27: Introducing the AccuTOX Program
Making a Global Impact | Defence Therapeutics INTRODUCING THE AccuTOX PROGRAM AccuTOX-001 (Solid Tumors: Multiple indications) 27
Slide 28: Enhances antigen uptake when chemically linked, but…
Making a Global Impact | Defence Therapeutics Enhances antigen uptake when chemically linked, but… Resting DCs Activated DCs Accum-Antigen + Resting DCs Cell death Accum + Antigen + 28
Slide 29: AccuTOX-001: An Accum Variant with Enhanced Potency
Making a Global Impact | Defence Therapeutics AccuTOX-001: An Accum Variant with Enhanced Potency (~30 fold increase) Original Accum AccuTOX-001 IC50: 95.94 μM IC50: 3.2 μM 100 100 80 80 Death Percentage of Percentage of Death Cells Survival 60 60 Percent 40 40 20 20 0 0 -1 0 1 2 3 -4 -2 0 2 4 Conce
Slide 30: AccuTOX-001 is Active Against Various Tumor Types
Making a Global Impact | Defence Therapeutics AccuTOX-001 is Active Against Various Tumor Types Original Accum AccuTOX-001 93% 100% EL4 EL4 81% 100% CT-26 CT-26 38% 100% B16 B16 84% 100% 4T1 4T1 Annexin-V Annexin-V 30
Slide 31: AccuTOX-001 Halts Tumor Development When Combined with Immune-Checkpoint Inhibitors
Making a Global Impact | Defence Therapeutics AccuTOX-001 Halts Tumor Development When Combined with Immune-Checkpoint Inhibitors 1200 100 Tumor volume (mm3) EL4 Percent survival PD-180 900 CTLA-4 60 Accum 600 Accum + PD-1 40 Accum + CTLA-4 300 Accum 20 + CD47 CD47 0 0 0 4 8 12 16 20 24 28 32 36 40
Slide 32: AccuTOX-001 Phase I trial (Canada): 3+3 Design
Making a Global Impact | Defence Therapeutics AccuTOX-001 Phase I trial (Canada): 3+3 Design (Phase I trial planned for Q1 2023) CHU Sherbrooke Phase I/IIA Phase II (Patient site 1) AccuTOX-001 + αPD-1 AccuTOX-001 + αPD-1 Dose Escalation 3+3 Design 1 mg/kg AccuTOX-001 McGill MUHC (Patient site 2) 5
Slide 33: Introducing the ADC Program: AccuADC-001
Making a Global Impact | Defence Therapeutics INTRODUCING THE ADC PROGRAM: AccuADC-001 (Solid Tumors: Breast Cancer) 33
Slide 34: What is an Antibody-Drug Conjugate (ADC)?
Making a Global Impact | Defence Therapeutics What is an Antibody-Drug Conjugate (ADC)? Antibody: • Targets specifically an overexpressed cancer receptor • High capacity to penetrate Linker: target cancer cells • Uncleavable/cleavable • DAR (Drug-antibody ratio) Drug: • Conjugation site on antibody
Slide 35: ADCs mode of action and limitations
Making a Global Impact | Defence Therapeutics ADCs mode of action and limitations T-DM1 Early endosome ADC degradation and drug release Late endosome and Multi-Vesicular Bodies Limited Drug diffusion Microtubule disruption Cell cycle arrest and apoptosis 35 ADCs are not completly degraded. ADC and d
Slide 36: Accum Enhances Therapeutic Potency of Trastuzumab-DM1 and Trastuzumab-αamanitin
Accum™ Enhances Therapeutic Potency of Making a Global Impact | Defence Therapeutics Trastuzumab-DM1 (AccuADC-001) and Trastuzumab-αamanitin SKBR3 JIMT-1 Accum™ increase potency of % Survival % Survival uncleavable Kadcyla® ADC by 10-100 folds Accum™ improve potency of cleavable -Trastuzumab- αamani
Slide 37: Accum for ADC Enhancement
Making a Global Impact | Defence Therapeutics Accum™ for ADC Enhancement Ongoing Steps: 8 best Accum™ variants • Defence Therapeutics Inc. has established a collaboration with the HUS Comprehensive Cancer Center in Helsinki, Finland, for the Screening of ACCUM™ variants with optimization of Defence'
Slide 38: Competitors in the Field
38 Making a Global Impact | Defence Therapeutics Competitors in the Field
Slide 39: Overall Summary
Making a Global Impact | Defence Therapeutics Overall Summary Accum™ molecule Bile acid NLS Highly Versatile Technology Enhance significantly the Easily applicable to protein- Molecules with Augment the anti-tumoral therapeutic potency of based vaccines anti-cancer properties potency of FDA-approved
Slide 40: Thank You
Making a Global Impact | Defence Therapeutics Thank You (514) 947-2272 info@defencetherapeutics.com www.defencetherapeutics.com 1680 - 200 Burrard Street, Vancouver, BC, V6C 3L6 Confidential 40
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