Adicet Bio, Inc. · NASDAQ:ACET
Adicet Bio — Merger or Acquisition (September 2020)
34 slides from Adicet Bio's merger presentation, Sep 16, 2020
Slide 1: Allogeneic Gamma Delta T Cells Engineered to Fight Cancer
Allogeneic Gamma Delta T Cells Engineered to Fight Cancer September 16, 2020 Exhibit 99.1
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding: future product development plans and projected timelines for the initiation and completi
Slide 3: Adicet Bio: Leaders in Engineered Gamma-Delta CAR-T Cell Therapy
Developing off-the-shelf, engineered Gamma-Delta (γδ) CAR-T cells for oncology and other indications Presence of γδ T cells in tumors was observed to strongly correlate with improved overall prognosis, survival and progression free survival Express T-cell and NK cell receptors, facilitating adaptive
Slide 4: Adicet Bio Post Merger Leadership Team
Adicet Bio Post Merger Leadership Team Chen Schor President and CEO Stewart Abbot, PhD Chief Scientific and Operating Officer Carrie Krehlik Chief Human Resource Officer Lloyd Klickstein, MD, PhD Chief Innovation Officer Francesco Galimi, MD, PhD Chief Medical Officer Nick Harvey Chief Financial Off
Slide 5: Improving Cancer Immunotherapy: γδ T Cells Correlate with Positive Clinical Outcomes
Improving Cancer Immunotherapy Presence of γδ T Cells Observed to Strongly Correlate with Positive Clinical Outcomes Meraviglia et al. 2017 Improved Disease Free Progression Colorectal Cancer γδ T cell hi γδ T cell lo γδ T cell lo / IFNγ lo Pan-Cancer: Improved Overall Prognosis Gentles et al. 2015
Slide 6: Building a Broad Pipeline of First in Class γδ CAR T Cell Therapy
NH: Non-Hodgkin’s ; HCC: hepatocellular carcinoma Building a Broad Pipeline of First in Class γδ CAR T Cell Therapy Program Target Indication Discovery Preclinical IND Phase 1 Phase 2 ADI-001 CD20 NH Lymphoma ADI-002 GPC3 HCC ADI-00x Undisclosed Solid Tumors ADI-00x Multiple Solid and Heme
Slide 7: Multiple Expected Near-Term Milestones
Multiple Expected Near-Term Milestones File IND for ADI-001 CD20 gamma-delta CAR-T Phase 1 clinical study in non-Hodgkin’s lymphoma ADI-001 expansion in DLBCL and/or MCL Phase 1 in HCC and other solid tumors Expand pipeline in oncology and other diseases File IND for ADI-002 GPC3 gamma-delta CAR-T D
Slide 8: ADI-001: Allogeneic CD20-CAR-γδ T Cell
ADI-001: Allogeneic CD20-CAR-γδ T Cell
Slide 9: Key Anticipated Advantages of Adicet's Allogeneic γδ1 T Cell Platform
Key Anticipated Advantages of Adicet’s Allogeneic γδ1 T Cell Platform Innate and adaptive immunity imparted by TCR and NK receptors May mitigate tumor relapse MHC-independent tumor targeting Off-the-shelf product, potential to re-dose No / low potential to cause GvHD Potent IFNγ production Potential
Slide 10: Adicet CAR γδ T Cell Platform Anticipated Advantages
Adicet CAR γδ T Cell Platform Anticipated Advantages: Engineered to address activity, tumor homing, safety, and COGs limitations Allogeneic CAR αβ T Cells Allogeneic CAR NK Cells Allogeneic CAR γδ T Cells Activity Innate anti-tumor response Adaptive anti-tumor response Active tumor homing Predominan
Slide 11: Large-Scale Manufacture of γδ T Cells
Large-Scale Manufacture of γδ T Cells Proprietary AM3579 activating antibody to expand γδ1 T cells, Proprietary Vectors, Proprietary Scalable Process
Slide 12: Anticipated Consistent Proprietary Large-Scale Expansion
Anticipated Consistent Proprietary Large-Scale Expansion Fully cGMP-compliant manufacturing process Available on demand for single or repeated dosing Consistent clinical-scale manufacture >6,000 fold expansion of Vδ1 T cells at clinical scale Highly cost efficient: Up to 1,000 doses / batch Data abo
Slide 13: CD20 CAR γδ T Cells Effectively Control Aggressive Lymphoma Tumors in Mice
CD20 CAR γδ T Cells Effectively Control Aggressive Lymphoma Tumors in Mice† Untreated animals succumb to highly aggressive tumors within 3 weeks 2nd generation (employing two co-stimulation domains) CD20 CAR γδ T cells effectively control multiple disseminated (iv) and localized (sc) tumors γδ T cel
Slide 14: CD20 γδ CAR-T Cells Control Repeat Lymphoma Challenges and Show Persistence
CD20 γδ CAR-T Cells Effectively Control Repeat Lymphoma Challenges and Demonstrate Functional Persistence for 100 Days Repeat tumor challenge is one of the most stringent tests of anti-tumor activity CD20 CAR γδ T cell treatment initiated* when tumor volume ≥ 200mm3 Excellent tumor control in all an
Slide 15: CD20 CAR γδ T Cells Proliferate in Response to Activation in Tumors
CD20 CAR γδ T Cells Proliferate in Response to Activation in Tumors Substantial and specific target-mediated proliferation of CD20 CAR γδ T cells in localized lymphoma tumors at 6 days post treatment † Blood Spleen Liver Bone marrow Tumor Cell Number T cell Proliferation Day 2 Post-treatment CAR-T γ
Slide 16: Absence of GvHD with CD20 CAR γδ T Cells
Intravenous Raji Tumor in SRG-15 Mice† Absence of GvHD with CD20 CAR γδ T Cells No GvHD observed in mice treated with γδ T cells γδ T cells not expected to induce GvHD in clinical study No gene editing required to overcome GvHD with γδ T cells αβ CAR-T cell group succumbed to GvHD αβ CART cells CAR
Slide 17: ADI-001 (Off-the-shelf CD20 CAR γδ T cells) Opportunity
ADI-001 (Off-the-shelf CD20 CAR γδ T cells) Opportunity Significant unmet medical need following CAR-T approvals Gr3+ CRS: 13-49%; Gr3+ neurotoxicity: 18-31% Limited number of specialized centers can treat patients; Suboptimal patient access Significant percentage of patients in pivotal trials didn’
Slide 18: First in Human Study for ADI-001
First in Human Study for ADI-001 (CD20 CAR γδ T cells) Follow-up Day -5 Day 0 Day 28 Month 12 Lymphodepletion Regimen: Flu/Cy Fludarabine: 30 mg/m2/d x 3 days, Cyclophosphamide 500 mg/m2/d x 3 days Phase 1 study design NHL patients relapsing from 2 or more prior lines of treatment 3 cohorts expected
Slide 19: ADI-002: Allogeneic GPC3-CAR-γδ T Cell for Solid Tumors
ADI-002: Allogeneic GPC3-CAR-γδ T Cell for Solid Tumors
Slide 20: Anticipated Advantages of Adicet's γδ CAR-T Cell Therapy in Solid Tumors
Anticipated Advantages of Adicet’s γδ CAR-T Cell Therapy in Solid Tumors Solid Tumor Challenges Adicet γδ CAR-T Cell Anticipated Advantage Avoiding autologous cell exhaustion / dysfunction Healthy CMV-negative donor derived product preserves Vδ1 proliferative capacity Potential for >30 population do
Slide 21: ADI-002: GPC3 Highly Expressed on Solid Tumors, Limited on Normal Tissues
ADI-002: GPC3 is highly expressed on a broad range of solid tumors, with limited expression levels on normal tissues Baumhoer et al., Am J Clin Pathol 2008;129:899-906 Ho et al., PLoS ONE 2012; 7: e37159 IHC Detection of GPC3 in human HCC vs normal liver Adicet Bio Confidential Tumor Non-tumor
Slide 22: Secretion of IL-15 Enhances Potency of ADI-002 Cells in Solid Tumors
Secretion of IL-15 Enhances Potency of ADI-002 Cells in Solid Tumors GPC3-CAR / sIL-15 γδ T cells control subcutaneous hepatocellular carcinoma growth in NSG mice
Slide 23: Dose Dependent Anti-Tumor Effect of Vδ1 CAR-T Cells in Liver Cancer Model
Dose Dependent Anti-Tumor Effect of Vδ1 CAR-T Cells with GPC3-Targeting sIL15 CAR γδ1 T Cells in Liver Cancer Model † GPC3-targeting chimeric antigen receptor construct also encodes secretion of IL15 Single dose CAR γδ T cell treatment was initiated* when tumor volumes reached ~200mm3 Excellent CAR
Slide 24: Anticipated Advantage of ADI-002 in HCC
Anticipated Advantage of ADI-002 in HCC Potential to address low target tumor densities CAR-dependent and CAR-independent tumor targeting Optimizing γδ T cells to overcome tumor microenvironment-mediated immunosuppression Enhancing persistence of CAR-γδ T cells Favorable preclinical results Opportun
Slide 25: TCR-L Platform: Intracellular Solid Tumor Targets
TCR-L Platform: Intracellular Solid Tumor Targets
Slide 26: TCR-L Platform: CAR-T Using Intracellular Solid Tumor Targets
TCR-L Platform: CAR-T Using Intracellular Solid Tumor Targets Challenge Lack of disease-specific cell surface targets in solid tumors TCR-L Proposed Solution Ability to target disease-specific intracellular proteins via peptide MHC complexes highly expands the target pool Unlikely to express on norm
Slide 27: Adicet Bio: Leaders in Engineered Gamma-Delta CAR-T Cell Therapy
Developing off-the-shelf, engineered Gamma-Delta (γδ) CAR-T cells for oncology and other indications Presence of γδ T cells in tumors was observed to strongly correlate with improved overall prognosis, survival and progression free survival Express T-cell and NK cell receptors, facilitating adaptive
Slide 28: Backup Slides
Backup Slides
Slide 29: CD20 CAR γδ T Cells Potently Kill Multiple Lymphoma Cell Lines in vitro
CD20 CAR γδ T Cells Potently Kill Multiple Lymphoma Cell Lines in vitro † Potent activity against tumors expressing high and low levels of CD20 Potent activity against tumors expressing HLA-Class 1 or HLA-Class 1 null CD20 CAR potentiates initial innate tumor recognition and killing Will-2 cells wer
Slide 30: Adicet: Leader in CAR & TCR Engineered γδ1 T cells
Adicet: Leader in CAR & TCR Engineered γδ1 T cells Adicet is a leader in the development of CAR-modified healthy donor-derived γδ1 T cell therapies Source: Adapted from Immuno-Oncology Technology 1 (2019) 3–10 Company T-cell type Source Gadeta αβ Blood GammaDelta Therapeutics γδ1 Skin/Blood TC Bioph
Slide 31: Intellectual Property
Intellectual Property Platform γδ T cell Expansion Multiple pending patent applications Compositions and methods of expansion/treatment Expiry 2035 to 2037 γδ T cell Optimized Constructs Multiple pending patent applications Compositions and methods of treatment Expiry 2038 to 2039 Novel Targeting Li
Slide 32: Regeneron Collaboration
Regeneron Collaboration In conjunction with Regeneron, Adicet discovers and develops γδ T cells engineered with CARs and TCRs Adicet has the right to use certain of Regeneron’s proprietary mice Five-year research collaboration signed July 2016 Adicet has the right to develop and commercialize the fi
Slide 33: Adicet's Key Anticipated Differentiation From γδ T cell Competitors
Adicet’s Key Anticipated Differentiation From γδ T cell Competitors Robust and practical proprietary antibody-based manufacturing method for γδ T cells Unique ability to selectively expand multiple γδ T cell subpopulations Large-scale expansion of blood-derived γδ T cells Production of highly potent
Slide 34: CAR-T Cell Therapy Journey
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 CAR-T Cell Therapy Journey 2015 Adicet Bio Founded ~2017 Yescarta approved by US FDA for r/r DLBCL 2012 U. Penn CART19 assets acquired by Novartis 2017 Kite Pharma acquired for $11.9B 2013 Juno Therapeutics founded 2009 Kite Pharm