Full Press Release Details
Allogeneic Gamma Delta T Cells
Engineered to Fight Cancer September 16, 2020 Exhibit 99.1
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 completion of preclinical and clinical trials and other activities of Adicet Bio, Inc. (the "Company" or "Adicet"); the potential for the results of ongoing preclinical or clinical trials and the
efficacy of Adicet's drug candidates; our expectations of the potential impact of COVID-19 on strategy, future operations, and the timing of our clinical trials, including potential impacts on enrollment and initiation; and future product
development and regulatory strategies, including with respect to specific indications. The use of words such as, but not limited to, "believe," "expect," "estimate," "project," "intend,"
"future," "potential," "continue," "may," "might," "plan," "will," "should," "seek," "anticipate," or "could" and
other similar words or expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Adicet's current beliefs,
expectations and assumptions regarding the future of Adicet's business, future plans and strategies, clinical results and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all
risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties
including but not limited to: (i) the outcome of any legal proceedings that may be instituted against the parties and others related to the merger agreement; (ii) unanticipated difficulties or expenditures relating to the merger, the response of
business partners and competitors to the announcement or completion of the merger, and/or potential difficulties in employee retention as a result of the announcement or completion of the merger; (iii) the combined company's listing on the
Nasdaq Global Market; (iv) the adequacy of the combined company's capital to support its future operations and its ability to successfully initiate and complete clinical trials; (v) the nature, strategy and focus of the combined company; (vi)
the difficulty in predicting the time and cost of development of Adicet's product candidates; (vii) Adicet's plans to develop and commercialize its product candidates, including, but not limited to, ADI-001 and ADI-002; (viii) the timing
of initiation of Adicet's planned clinical trials; (ix) the timing of the availability of data from Adicet's clinical trials; (x) the timing of any planned investigational new drug application or new drug application; (xi) Adicet's
plans to research, develop and commercialize its current and future product candidates; (xii) Adicet's ability to enter into new collaborations, and to fulfill its obligations under any such collaboration agreements; (xiii) the clinical
utility, potential benefits and market acceptance of Adicet's product candidates; (xiv) Adicet's commercialization, marketing and manufacturing capabilities and strategy; (xv) Adicet's ability to identify additional products or
product candidates with significant commercial potential and to expand its pipeline in oncology and other diseases; (xvi) developments and projections relating to Adicet's competitors and its industry; (xvii) the impact of government laws and
regulations; (xviii) the impact of public health epidemics affecting countries or regions in which we have operations or do business, such as COVID-19, which has been labeled a pandemic by the World Health Organization, the timing and anticipated
results of our clinical trials; (xix) the risk that the results of our clinical trials may not be predictive of future results in connection with future clinical trials; (xx) the timing and outcome of our planned interactions with regulatory
authorities; (xxi) Adicet's ability to protect its intellectual property position; (xxii) Adicet's estimates regarding future revenue, expenses, capital requirements and need for additional financing; and (xxiii) those risks detailed in
resTORbio's, Inc.'s definitive proxy statement/prospectus/information statement filed with the SEC on August 21, 2020, as well as discussions of potential risks, uncertainties, and other important factors in Adicet's subsequent
filings with the Securities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made. None of Adicet, nor its affiliates, advisors or representatives, undertake any obligation to publicly update or
revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. Industry and Market Information Information regarding market share, market position and industry data pertaining to
Adicet's business contained in this presentation consists of estimates based on data and reports compiled by industry professional organizations and analysts and Adicet's knowledge of their industry. Although Adicet believes the industry
and market data to be reliable, this information could prove to be inaccurate. You should carefully consider the inherent risks and uncertainties associated with the market and other industry data contained in this presentation. Forward-looking
information obtained from third-party sources is subject to the same qualifications and the additional uncertainties as the other forward-looking statements in this presentation.
Developing off-the-shelf, engineered
Gamma-Delta ( ) CAR-T cells for oncology and other indications Presence of 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 and innate anti-tumor immune responses with more limited ability for tumor escape Intrinsically home to and function in tissues and solid malignancies Allogeneic and off-the-shelf with potential to re-dose
patients and no expected GvHD Potential for outpatient administration Proprietary T Cell Receptor-Like (TCR-L) monoclonal platform targeting intracellular targets presented on MHC complexes $123 million pro forma cash, cash equivalent and marketable
securities June 30, 2020 Multiple near-term milestones Key Investors: OrbiMed, Novartis, JNJ, Regeneron, aMoon Adicet Bio: Leaders in Engineered Gamma-Delta CAR-T Cell Therapy CAR: Chimeric Antigen Receptors; NK: Natural Killer; GvHD: Graft Versus
Host Disease; MHC: Major Histocompatibility Complex; NKG2D: NK Group 2D; NCR=Natural Cytotoxicity Receptors; DNAM-1: DNAX accessory molecule-1
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
Improving Cancer Immunotherapy
Presence of T Cells Observed to Strongly Correlate with Positive Clinical Outcomes Meraviglia et al. 2017 Improved Disease Free Progression Colorectal Cancer T cell hi T cell lo T cell lo /
IFN lo Pan-Cancer: Improved Overall Prognosis Gentles et al. 2015 Godder et al. 2007 Post-HSCT Improved Survival T cell hi T cell lo Overall Survival HSCT: Hematopoietic Stem Cell Transplantation
NH: Non-Hodgkin's ; HCC:
hepatocellular carcinoma Building a Broad Pipeline of First in Class 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
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 DLBCL: Diffuse Large B Cell Lymphoma; MCL: Mantle Cell Lymphoma
Key Anticipated Advantages of
Adicet's Allogeneic 1 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 IFN production Potential for integrin-mediated trafficking to solid tumors Scalable manufacturing from healthy donors Not compromised by patient's immune system dysfunction MICA / B B7-H6, etc. MHC- unrestricted antigens CD20
Nectin-2, etc. Galectin-3, NKp44L, etc.
Platform Anticipated Advantages: Engineered to address activity, tumor homing, safety, and COGs limitations Allogeneic CAR T Cells Allogeneic CAR NK Cells Allogeneic CAR T Cells Activity Innate anti-tumor response Adaptive
anti-tumor response Active tumor homing Predominantly activating receptor expression (Limited number) (Balance with inactivating) Preclinical persistence by repeat tumor challenge Prognostic value of tumor infiltration Safety Low GvHD risk (Requires
TCR deletion) Low risk of cytokine release syndrome grade 3 risk COGS No gene editing required (May affect efficacy) Scalable manufacturing Limited without exhaustion
Large-Scale Manufacture of
T Cells Proprietary AM3579 activating antibody to expand 1 T cells, Proprietary Vectors, Proprietary Scalable Process
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 V 1 T cells at clinical scale Highly cost efficient: Up to
1,000 doses / batch Data above are from full-scale clinical productions conducted by Adicet and cGMP-compliant contract manufacturing organization
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 T cells effectively control multiple
disseminated (iv) and localized (sc) tumors T cell treatment initiated* when tumor volume 200mm3 Intravenous Raji Tumor Growth * Subcutaneous Raji Tumor Growth * -5 0 5 10 15 20 25 30 35 0 1 10 10 2 10 10 3 10 10
4 10 10 5 10 10 6 10 10 7 10 10 M e a n T o t a l F l u x ( p / s ) + / - S E M Intravenous Granta Tumor Growth * Subcutaneous Mino Tumor Growth * internal Adicet study
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 T cell treatment initiated* when tumor volume
200mm3 Excellent tumor control in all animals at day 55 Secondary tumor challenge at day 60 CD20 CAR T demonstrate functional persistence and control tumor growth to 100 days * internal Adicet study In Vivo
Subcutaneous Raji Tumor Killing 1 Tumor Challenge 2 Tumor Challenge Mean Tumor Volume (mm3)+/- SEM
Proliferate in Response to Activation in Tumors Substantial and specific target-mediated proliferation of CD20 CAR 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 Day 6 Post-treatment CAR-T Blood Spleen Liver Tumor Bone marrow T cell Proliferation T cell Proliferation Day 6 Post-treatment CAR-T internal Adicet study
103 104 105 106 103 104 105 106 103 104 105 106
Intravenous Raji Tumor in SRG-15
Mice Absence of GvHD with CD20 CAR T Cells No GvHD observed in mice treated with T cells T cells not expected to induce GvHD in clinical study No gene editing required to overcome GvHD with
T cells CAR-T cell group succumbed to GvHD CART cells CAR T cells Tumor alone Days Post Treatment Percentage Surviving internal Adicet study; SRG-15 mice express human IL-15 transgene
ADI-001 (Off-the-shelf CD20 CAR
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't receive cells (primarily due to mfg. challenges or wait time) 40% of patients treated with approved autologous CD19 CAR T therapy show durable responses ADI-001 Target product profile Effective (ORR, PFS/OS)
in CD20 expressing NHL Facilitating adaptive and innate anti-tumor immune responses with more limited ability for tumor escape Potential alternative to autologous therapies and/or line of therapy before/after CD19 cell therapy relapse Significantly
lower cytokine release syndrome; No GvHD Potential for outpatient administration Sources: Kymriah and Yescara package inserts; Neelapu et al. N Eng J Med 2017
First in Human Study for ADI-001
(CD20 CAR 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 for dose escalation/safety Up to 50 patients at the selected dose Optional ADI-001 retreatment Potential DLBCL dose expansion / Pivotal study Potential MCL dose expansion / Pivotal study Long-term follow-up study Lympho-
depletion Treatment Enrollment ADI-001 Infusion Response & Safety Assessment End of Study Response & Safety Assessment Months 3, 6, 9, 12 () () Dose escalation study
GPC3-CAR- T Cell for Solid Tumors
Anticipated Advantages of
Adicet's CAR-T Cell Therapy in Solid Tumors Solid Tumor Challenges Adicet CAR-T Cell Anticipated Advantage Avoiding autologous cell exhaustion / dysfunction Healthy CMV-negative donor derived product preserves
V 1 proliferative capacity Potential for >30 population doublings ex vivo / in vivo Specific tumor-induced activation & proliferation Activation-induced PD-1 expression is reversible without exhaustion CAR-designs minimize tonic
signaling Cells Infiltration into Tumor Chemokine receptor and adhesion molecule mediated infiltration Immunosuppressive Tumor Microenvironment Further engineering can improve responses to tumor microenvironment factors T cells can
survive and function in hypoxic / low nutrient conditions Loss of HLA or Target Antigen(s) Expression HLA-independent T cell innate receptor-mediated tumor recognition Paucity of tractable targets Ability to target intracellular
antigens CMV: Cytomegalovirus; HLA: Human Leukocyte Antigen
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
Secretion of IL-15 Enhances Potency
of ADI-002 Cells in Solid Tumors GPC3-CAR / sIL-15 T cells control subcutaneous hepatocellular carcinoma growth in NSG mice
Dose Dependent Anti-Tumor Effect of
V 1 CAR-T Cells with GPC3-Targeting sIL15 CAR 1 T Cells in Liver Cancer Model GPC3-targeting chimeric antigen receptor construct also encodes secretion of IL15 Single dose CAR T cell treatment was initiated*
when tumor volumes reached ~200mm3 Excellent CAR T dose-dependent control of tumor growth Tumor alone GPC3 CAR T - low dose GPC3 CAR T- medium dose GPC3 CAR T- high dose Adicet Bio
Confidential internal Adicet study
Anticipated Advantage of ADI-002 in
HCC Potential to address low target tumor densities CAR-dependent and CAR-independent tumor targeting Optimizing T cells to overcome tumor microenvironment-mediated immunosuppression Enhancing persistence of CAR- T cells
Favorable preclinical results Opportunities in multiple tumor types Adicet Bio Confidential
TCR-L Platform: Intracellular Solid
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 normal cells Adicet has generated multiple TCR-Like (TCR-L) antibodies to various intracellular targets in key solid tumor indications Mimic TCR specificity with higher affinity of mAbs scFv for chimeric antigen receptors for