Slide 1: Virtual R&D Event November 10, 2022
Virtual R&D Event November 10, 2022
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains "forward-looking statements" of Adicet Bio, Inc. (Adicet) within the meaning of the Private Securities Litigation Reform Act of 1995 relating to business and operations of Adicet. These forward-looking statements include, but are not limited to,
Slide 3: Agenda
Agenda Introduction Chen Schor Preclinical Program Overview Blake Aftab, Ph.D. Perspectives Marco Davila, M.D., Ph.D. Closing Remarks Chen Schor Q&A Chen Schor Blake Aftab, Ph.D. Marco Davila, M.D., Ph.D. Francesco Galimi, M.D., Ph.D. Nick Harvey Chen Schor President and CEO Blake Aftab, Ph.D. Chief
Slide 4: Leaders in Developing Allogeneic CAR and CAd Therapies to Fight Cancer
Leaders in Developing Allogeneic CAR and CAd γδ T Cell Therapies to Fight Cancer Chen Schor, President and CEO
Slide 5: Adicet Highlights: Leading The Way With Therapies To Fight Cancer
Adicet Highlights: Leading The Way With γδ T Cell Therapies To Fight Cancer CR: Complete response; CRS: Cytokine release syndrome; γδ: Gamma delta; Gr3: Grade three; ICANS: Immune effector cell-associated neurotoxicity syndrome; IP: Intellectual property; NHL: Non-Hodgkin's lymphoma 2015 Adicet Bio
Slide 6: Adicet CAR Platform Potential Advantages
Adicet CAR γδ T Cell Platform Potential Advantages: Engineered to Address Activity, Tumor Homing, Safety, and COGs Limitations CAR γδ T Cells Key Supporting Data Activity* Innate anti-tumor response PRE-CLINICAL: Nishimoto et. al. Clinical & Translational Immunology 2022; Makkouk et. al. JITC 2021;
Slide 7: Opportunity for highly differentiated clinical benefits
Opportunity for highly differentiated clinical benefits Unmet medical need Current standard of care Competitive landscape Armor to preserve activity in immuno- suppressive tumor microenvironment Follow γδ1 T cell tissue residence and infiltration in solid tumors Engineer and enhance targeting with C
Slide 8: Building a Broad Pipeline of First-in-Class CAR and CAd Product Candidates
Program Target Potential Indication Discovery Preclinical IND-Enabling Phase 1 Ph 2/3 ADI-001 CD20 NHL ADI-925 Tumor stress ligands Multiple Solid / Heme ADI-xxx CD70 RCC & Other ST / Heme ADI-xxx PSMA mCRPC ADI-xxx B7-H6 Multiple Solid / Heme ADI-xxx Undisclosed Multiple Myeloma ADI-xxx Undisclosed
Slide 9: ADI-925: First-in-Class Enhanced γδ T Cell Product Candidate
ADI-925: First-in-Class Enhanced γδ 1 T Cell Product Candidate for Multiple Heme and Solid Tumors ADI-925 may provide these benefits to cancer patients We engineered our γδ 1 T cells to significantly enhance their intrinsic innate and adaptive anti-tumor activity by rewiring signaling pathways in th
Slide 10: Preclinical Pipeline Overview
Preclinical Pipeline Overview Blake Aftab, Ph.D. Chief Scientific Officer
Slide 11: Building a Broad Pipeline of First-in-Class CAR and CAd Product Candidates
Building a Broad Pipeline of First-in-Class CAR and CAd γδ T Cell Product Candidates Program Target Potential Indication Discovery Preclinical IND-Enabling Phase 1 Ph 2/3 ADI-001 CD20 NHL ADI-925 Tumor stress ligands Multiple Solid / Heme ADI-xxx CD70 RCC & Other ST / Heme ADI-xxx PSMA mCRPC ADI-xxx
Slide 12: ADI-925: Engineered γδ1 Chimeric Adaptor T Cell Product Candidate
ADI-925: Engineered γδ1 Chimeric Adaptor T Cell Product Candidate ADI-925 is designed to enhance the innate and adaptive anti-tumor activity of Vδ1 T cell ADI-925 is an engineered Chimeric Adapter (CAd) Vδ1 T cell therapy candidate targeting stress ligands, including MICA/MICB & ULBP1-6 expressed on
Slide 13: First-in-class CAd Enhancement of Intrinsic γδ T Cell Activity
First-in-class CAd Enhancement of Intrinsic gd T Cell Activity ADI: Adicet Bio, ULBP: UL16-binding protein
Slide 14: Tumor Stress Ligands Targeted by ADI-925 Are Ubiquitously Expressed
Tumor Stress Ligands Targeted by ADI-925 Are Ubiquitously Expressed Across a Broad Range of Indications Expression of stress ligands across indications is coupled to drivers of tumor formation1 Stress Ligands Expression of stress ligands present in broad range of primary tumor specimens AML, MM, mel
Slide 15: ADI-925 Targets a Broad Panel of Malignancies
ADI-925 Targets a Broad Panel of Malignancies ADI-925 effectively enhanced cytotoxic potency of γδ T cells in broad panel of cancer cell lines Cad+Vδ1 T cells Vδ1 T cells Vδ1+ DAP10wt T cells Enhancement was primarily driven via endogenous NKG2D PRESENTED AT SITC 2022 Herrman et. al. SITC (2022)
Slide 16: ADI-925 Demonstrated Enhanced Potency of γδ T Cells
ADI-925 Demonstrated Enhanced Potency of γδ T Cells Potent Killing with CAd Engineered γδ T Cells HCC Xenograft PLC/PRF/5 Cell Line PRESENTED AT SITC 2022 HCC Cell Line HepG2 Herrman et. al. SITC (2022) Potent Activity in Solid Tumor Models Tumor Alone CAd+ Vδ1 T cells Tumor Alone Positive Control-C
Slide 17: ADI-925 Illustrated Preferential Homing and Expansion Within Tumors
ADI-925 Illustrated Preferential Homing and Expansion Within Tumors Homing ADI-925 actively homed and biodistributed to relevant tissues Expansion Tissue residence of ADI-925 and selective expansion within tumor tissues Proliferation ADI-925 expansion coupled to selective γδ T cell proliferation wit
Slide 18: ADI-925: Opportunity For Differentiation
ADI-925: Opportunity For Differentiation OS: Overall survival Opportunity for ADI-925 to address broad landscape Enhanced natural cytotoxic effector function Targeting multiple stress antigens addressing tumor heterogeneity Broad, clinically relevant homing in solid tumors Prominent cell expansion c
Slide 19: Building a Broad Pipeline of First-in-Class CAR and CAd Product Candidates
Building a Broad Pipeline of First-in-Class CAR and CAd γδ T Cell Product Candidates Program Target Potential Indication Discovery Preclinical IND-Enabling Phase 1 Ph 2/3 ADI-001 CD20 NHL ADI-925* Tumor stress ligands Multiple Solid / Heme ADI-xxx CD70 RCC & Other ST / Heme ADI-xxx PSMA mCRPC ADI-xx
Slide 20: Armored CD70 CAR Opportunity For Differentiation
Armored CD70 CAR γδ T Cell Opportunity For Differentiation ADC: Antibody-drug conjugate; AML: Acute myeloid leukemia; mAb: Sonoclonal antibody; RCC: Renal cell carcinoma; SD: Stable disease; TME: Tumor microenvironment Opportunity for Adicet and γδ T cells Response to low antigen density by design w
Slide 21: Adicet's Armored CD70 CAR γδ T Cell
Adicet’s Armored CD70 CAR gd T Cell Targeting CD70 via CD27-ligand has shown superiority to scFv CARs1 Innate and adaptive targeting mechanisms associated with activity in AML and RCC indications Armoring via dominant negative receptor; addresses TGFb in TME2 Lead CAR demonstrated potency and improv
Slide 22: Armored CD70 CAR γδ T Cells Generated with High Efficiency
Armored CD70 CAR γδ T Cells Generated with High Efficiency CD70 CAR γδ T cells produced with high transduction efficiency Phenotype similar to that of Adicet’s established ADI-001 process1 Production of CD70 CAR γδ T cells does not indicate fratricide No Evidence of Fratricide Impeding Manufacture H
Slide 23: CD70 CAR γδ T Cells Retained Cytotoxicity Across Range of Target Expression
CD70 CAR γδ T Cells Retained Cytotoxicity Across Range of Target Expression CD27-derived targeting of CD70 resulted in activation and anti-tumor activity across range of target antigen densities Target recognition applicable across range of indications and cell lines Lung Adenocarcinoma, Renal Cell
Slide 24: TGFb Plays a Key Immunosuppressive Factor in TME
TGFb Plays a Key Immunosuppressive Factor in TME What is the purpose for armoring cells? High levels of TGFb in tumor microenvironment resulted in differentially downregulated (red) or upregulated (blue) genes Alterations propagate immunosuppressive effects1 and may blunt efficacy of immunotherapies
Slide 25: Armoring CD70 CAR Improved Resilience
Armoring CD70 CAR γδ T Cell Improved Resilience PRESENTED AT SITC 2022 Add TGFb-DNR Armor TGFβ alters effector activation profile Lamture et. al. SITC (2022) CD70 CAR
Slide 26: Armoring CD70 CAR Improved Resilience
Armoring CD70 CAR γδ T Cell Improved Resilience Add TGFb-DNR Armor Resilient activation profile in presence of TGFβ CD70 CAR + TGFb-DNR TGFβ alters effector activation profile PRESENTED AT SITC 2022 Lamture et. al. SITC (2022) CD70 CAR
Slide 27: Armor Associated with Resilient Serial Killing and Functional Persistence
Armor Associated with Resilient Serial Killing and Functional Persistence in Rechallenge Model Armoring CD70 CAR γδ T Cell Improved Resilience PRESENTED AT SITC 2022 Add TGFb-DNR Armor Resilient activation profile in presence of TGFβ CD70 CAR + TGFb-DNR TGFβ alters effector activation profile Challe
Slide 28: CD70 CAR γδ T Cells Demonstrated Activity In Vivo
CD70 CAR γδ T Cells Demonstrated Activity In Vivo and Proliferated Within Tumors CD70 CAR γδ T cells demonstrated robust tumor growth inhibition Anti-tumor activity associated with CAR γδ T cell tumor infiltration and proliferation within the tumor bulk Tumor Infiltration and Proliferation of γδ CAR
Slide 29: Armored CD70 CAR γδ T Cells: Summary and Next Steps
Armored CD70 CAR γδ T Cells: Summary and Next Steps Armored CD70 CAR gd T cell program produced a compelling lead that warrants further development Program on-track for achieving differentiated target profile and proceeding to IND-candidate nomination Additional data expected to be presented in 2023
Slide 30: Building a Broad Pipeline of First-in-Class CAR and CAd Product Candidates
Building a Broad Pipeline of First-in-Class CAR and CAd γδ T Cell Product Candidates Program Target Potential Indication Discovery Preclinical IND-Enabling Phase 1 Ph 2/3 ADI-001 CD20 NHL ADI-925* Tumor stress ligands Multiple Solid / Heme ADI-xxx CD70 RCC & Other ST / Heme ADI-xxx PSMA mCRPC ADI-xx
Slide 31: Armored PSMA CAR Opportunity For Differentiation
Armored PSMA CAR γδ T Cell Opportunity For Differentiation Opportunity for Adicet and γδ T cells Potent CAR construct active against heterogeneous PSMA Three mechanisms of action designed to address tumor heterogeneity Homing of γδ T cells documented in mCRPC Inclusion of armoring to address suppres
Slide 32: Armored PSMA CAR Program
Armored PSMA CAR γδ T Cell Program Lead candidate targeting PSMA demonstrated improved characteristics versus benchmark1 Heterogeneous PSMA Armoring technology via TGFb-DNR improved activity, serial killing, and functional resilience Complimentary Natural Cytotoxicity Receptors HLA Independent TCR N
Slide 33: Adicet's Lead PSMA CAR Construct Demonstrated Improved Cytotoxicity Over Benchmark
Adicet’s Lead PSMA CAR Construct Demonstrated Improved Cytotoxicity and Targeting Over Benchmark Cytotoxicity at Low E:T Ratio Target-Associated Proliferation Lead CAR Construct demonstrated: Efficient activation of NFAT signaling Recognition of intermediate/ heterogeneous PSMA expression Broad targ
Slide 34: Armored PSMA CAR Program Improved Resilience with TGFb-DNR
Armored PSMA CAR γδ T Cell Program Improved Resilience with TGFb-DNR PRESENTED AT SITC 2022 Armor Associated with Resilient Serial Killing and Functional Persistence Ramadoss et. al. SITC (2022)
Slide 35: Armored PSMA CAR Program In Vivo Activity and Next Steps
Armored PSMA CAR γδ T Cell Program In Vivo Activity and Next Steps Armored PSMA CAR γδ T cell program demonstrated significant antitumor activity across mCRPC models Program lead is progressing through efficacy and manufacturing assessment for IND-candidate confirmation Program Lead Benchmark 22Rv1
Slide 36: Building a Broad Pipeline of First-in-Class CAR and CAd Product Candidates
Building a Broad Pipeline of First-in-Class CAR and CAd γδ T Cell Product Candidates Program Target Potential Indication Discovery Preclinical IND-Enabling Phase 1 Ph 2/3 ADI-001 CD20 NHL ADI-925* Tumor stress ligands Multiple Solid / Heme ADI-xxx CD70 RCC & Other ST / Heme ADI-xxx PSMA mCRPC ADI-xx
Slide 37: Armored B7-H6 CAR Opportunity For Differentiation
Armored B7-H6 CAR γδ T Cell Opportunity For Differentiation Opportunity for Adicet and γδ T cells Potential to be first-in-class B7-H6 targeted cell therapy product into clinic Designed to retain activity in presence of shed antigen and armored against TME High level of homing for Vd1 T cells in GI
Slide 38: Armored B7-H6 CAR Program
Armored B7-H6 CAR γδ T Cell Program Library of de novo CAR constructs screened for binding characteristics and improved performance versus benchmark1 CAR optimization underway to define lead construct in 2023 Iterative and novel armoring enhancements being explored Complimentary Natural Cytotoxicity
Slide 39: B7-H6 CARs Applicable Across Range of Indications
B7-H6 CAR γδ T Cells Applicable Across Range of Indications B7-H6 CAR γδ T cells demonstrated anti-tumor activity across range of target antigen densities and indications Adicet’s tailored scFv screening strategy has yielded CAR leads resilient to inhibition by shed antigen compared to benchmark1 An
Slide 40: B7-H6 CARs Demonstrated Anti-Tumor Activity and Improved Polyfunctional Strength
B7-H6 CAR γδ T Cells Demonstrated Anti-Tumor Activity and Improved Polyfunctional Strength B7-H6 CAR γδ T cells demonstrated improved polyfunctional strength compared to benchmark CAR1 Efficacy studies support potent anti tumor activity Lead discovery proceeding with additional armoring technologies
Slide 41: Summary of Pipeline and 2022 SITC Data
Summary of Pipeline and 2022 SITC Data Blake Aftab, Ph.D. Chief Scientific Officer
Slide 42: Building a Broad Pipeline of First-in-Class CAR and CAd Product Candidates
Program Target Potential Indication Discovery Preclinical IND-Enabling Phase 1 Ph 2/3 ADI-001 CD20 NHL ADI-925* Tumor stress ligands Multiple Solid / Heme ADI-xxx CD70 RCC & Other ST / Heme ADI-xxx PSMA mCRPC ADI-xxx B7-H6 Multiple Solid / Heme ADI-xxx Undisclosed Multiple Myeloma ADI-xxx Undisclose
Slide 43: Perspectives: Adicet Pipeline
Marco Davila, M.D., Ph.D. Roswell Park Comprehensive Cancer Center Perspectives: Adicet γδ T Cell Pipeline
Slide 44: Perspectives: Question 1
Perspectives Marco Davila M.D., Ph.D. Associate Director and SVP Translational Research Roswell Park Comprehensive Cancer Center Adicet Bio Scientific Advisory Board Member Question 1: Can you share your preliminary thoughts on the pipeline we presented today? What do these engineered γδ1 T cell pro
Slide 45: Perspectives: Question 2
Perspectives Marco Davila M.D., Ph.D. Associate Director and SVP Translational Research Roswell Park Comprehensive Cancer Center Adicet Bio Scientific Advisory Board Member Question 2: Can you share your thoughts on ADI-925 and the chimeric adaptor technology? Question 1: Can you share your prelimin
Slide 46: Perspectives: Question 3
Perspectives Marco Davila M.D., Ph.D. Associate Director and SVP Translational Research Roswell Park Comprehensive Cancer Center Adicet Bio Scientific Advisory Board Member Question 3: With CD70 and PSMA, can you provide your perspectives in the context of previous approaches to these targets? Quest
Slide 47: Closing Remarks
Closing Remarks Chen Schor, President and CEO
Slide 48: ASH clinical update on Phase 1 study in R/R aggressive B-cell NHL
Sattva Neelapu, M.D. Department of Lymphoma-Myeloma Division of Cancer Medicine The University of Texas, MD Anderson Cancer Center Adicet Bio to discuss recent data from ongoing Phase 1 clinical study in R/R aggressive B-cell NHL When: Sunday, December 11 at 8:00 a.m. CT/ 9:00 a.m. ET
Slide 49: Advanced Therapies CR Rate Over Time in 3L and 4L Aggressive NHL
Advanced Therapies CR Rate Over Time in 3L and 4L Aggressive NHL ~50% 43% ~30% ~30% Autologous alpha-beta CAR T in 3L DLBCL patients Autologous alpha-beta CAR T in 3L DLBCL patients N Engl J Med. (2017) December 28; 377(26): 2531–2544. J Clin Oncol 38:3095-3106. Yescarta EPAR Public Assessment Repor
Slide 50: Advanced Therapies CR Rate Over Time in 3L and 4L Aggressive NHL
est. best case Advanced Therapies CR Rate Over Time in 3L and 4L Aggressive NHL ~50% 43% ~34% ~20%* ~30%* ~30% ~30% Autologous alpha-beta CAR T in 3L DLBCL patients CD20 bispecifics in 4L DLBCL patients post autologous CAR T Autologous alpha-beta CAR T in 3L DLBCL patients N Engl J Med. (2017) Decem
Slide 51: Anticipated Near-Term Milestones
Anticipated Near-Term Milestones ADI-001 Phase 1 Study in R/R NHL Complete dose escalation through DL4; backfill enrollment to DL3 ASH clinical update Dec. 11 at 8:00 a.m. CT Establish recommended Phase 2 dose by end of 2022 BLA: Biologics License Application; DL: Dose level; EMA: European Medicines
Slide 52: Q&A
> Adicet Bio Q&A
Slide 53: Leaders in Developing Allogeneic CAR and CAd Therapies to Fight Cancer
Leaders in Developing Allogeneic CAR and CAd γδ T Cell Therapies to Fight Cancer