Defence Therapeutics Inc Class A · CSE:DTC
Defence Therapeutics Inc Class A — Investor Presentation (January 2023)
48 slides from Defence Therapeutics Inc Class A's investor presentation, January 2023
Slide 1: Making a Global Impact
Making a Global Impact | Defence Therapeutics Making A Global Impact Developing Unique Immuno- Oncology Solutions Slide Deck (January 2023) 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: 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 AccuTOX-IN001 Lung Cancer
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-Q3 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
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 Q2-Q3 2023) AccuVAC-PT007 Dose Escalation 3+3 Design Dose 1 AccuVAC-PT007 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 Q2 2023) Phase I/IIA Phase II AccuTOX-001 + αPD-1 AccuTOX-001 + αPD-1 Dose Escalation 3+3 Design 1 mg/kg AccuTOX-001 City of Hope (Patients site) 5 mg/kg 5 mg/kg AccuTOX-001 AccuTO
Slide 33: AccuTOX-IN for lung cancer
Making a Global Impact | Defence Therapeutics AccuTOX-IN for lung cancer When cancer starts in the lungs, it can spread to lymph nodes or other organs in the body. This cancer is usually grouped into two main types called small cell and non-small cell carcinoma. Types of Treatments - Surgery - Chemo
Slide 34: Current limitations of lung cancer therapy
Making a Global Impact | Defence Therapeutics Current limitations of lung cancer therapy - Response rates can be low - Response duration short - Poor survival - Rapid tumor spreading - Quality of life deterioration - Treatment toxicity 34
Slide 35: The global lung cancer therapeutics market
Making a Global Impact | Defence Therapeutics The global lung cancer therapeutics market The market size was estimated at USD 27.57 billion in 2021 and it is expected to surpass around USD 55.6 billion by 2030 with a registered CAGR of 8.11% from 2022 to 2030. 35
Slide 36: Identifying The Maximum Tolerated Dose and Best Regimen for Intranasal Administration
Making a Global Impact | Defence Therapeutics Identifying The Maximum Tolerated Dose and The Best Regimen for AccuTOX Intranasal Administration Stage 1 - Single Injection Stage 2 - Repetitive Injection 15 μl 50 μl 15 μl 50 μl √ 5mg/kg √ √ 1mg/kg √ X 10mg/kg X √ 3mg/kg √ X 15mg/kg X X 5mg/kg X X 20mg
Slide 37: AccuTOX/Anti-PD-1 Intranasal Administration Greatly Reduces Lung Nodule Numbers
Making a Global Impact | Defence Therapeutics AccuTOX/Anti-PD-1 Intranasal Administration Greatly Reduces Lung Nodule Numbers B16F10 Number of Nodule/Lung 80 Transplantation 0 (IV) AccuTOX/PD1 7 60 14 Lung Analysis 40 21 20 Days 0 Ctl PD-1 AccuTOX AccuTOX + PD-1 37
Slide 38: Introducing the ADC Program: AccuADC-001
Making a Global Impact | Defence Therapeutics INTRODUCING THE ADC PROGRAM: AccuADC-001 (Solid Tumors: Breast Cancer) 38
Slide 39: 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 40: 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 40 ADCs are not completly degraded. ADC and d
Slide 41: 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 42: Accum for ADC Enhancement Ongoing Steps
Making a Global Impact | Defence Therapeutics Accum™ for ADC Enhancement Ongoing Steps: 8 best Accum™ variants • Defence Therapeutics Inc. has established a service agreement with the HUS Comprehensive Cancer Center in Helsinki, Finland, Screening of ACCUM™ variants with for the optimization of Defe
Slide 43: Competitors in the Field
43 Making a Global Impact | Defence Therapeutics Competitors in the Field
Slide 44: Introducing the AccuVAC-mRNA Program
Making a Global Impact | Defence Therapeutics INTRODUCING THE AccuVAC- mRNA PROGRAM: AccuVAC-mRNA001 (Solid Tumors: undisclosed) 44
Slide 45: The concept of mRNA vaccination
Making a Global Impact | Defence Therapeutics The concept of mRNA vaccination mRNA - Limited entry inside target cells - Endosomal entrapment Applying the AccumTM - Degradation To bypass these limitations mRNA Translation Protein To be picked and processed by antigen-presenting cells 45
Slide 46: Initial vaccination studies using naked mRNA
Making a Global Impact | Defence Therapeutics Initial vaccination studies using "naked" mRNA 100000 Antibody Titer (OVA) Adjuvant OVA mRNA 10000 * * OVA mRNA + Adjuvant * 1000 100 Studies are ongoing to compare "naked" to Accum- linked mRNA vaccines. 10 Wk 0 Wk 2 Wk 4 46
Slide 47: 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 /mRNA-based vaccines anti-cancer properties potency of FDA-ap
Slide 48: 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 48
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