UNITED STATES
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FORM
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
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Item 7.01 Regulation FD Disclosure.
On November 10, 2022, Adicet Bio, Inc. (“Adicet”) held its Virtual Research and Development (“R&D”) Day. In connection with the R&D Day, Adicet has made its presentation from the R&D Day available on its website at investor.adicetbio.com/events-and-presentations/events. A copy of the presentation is also furnished herewith as Exhibit 99.1 to this Current Report on Form 8-K.
The information in this Item 7.01, including Exhibit 99.1 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 8.01 Other Events.
Adicet’s ongoing research efforts are focused on “off-the-shelf” gamma delta T cells, engineered with chimeric antigen receptors (CARs) and adaptors (CAds), to enhance selective tumor targeting and facilitate innate and adaptive anti-tumor immune response for durable activity in patients.
On November 10, 2022, Adicet provided the below updates regarding its product candidates and R&D programs:
Item 9.01 Exhibits.
(d) Exhibits
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99.1 |
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R&D Day Presentation by Adicet Bio, Inc. on November 10, 2022, furnished herewith. |
104 |
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Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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ADICET BIO, INC. |
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Date: November 10, 2022 |
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/s/ Nick Harvey |
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Nick Harvey |
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Chief Financial Officer |
Virtual R&D Event November 10, 2022
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, express or implied statements regarding the potential safety, durability, tolerability and therapeutic effects of ADI-001 and preclinical programs, including the implementation, timing and success of ADI-001, ADI-925 and the additional preclinical programs in Adicet’s pipeline; plans and timing for the release of additional clinical data from Adicet's Phase 1 trial of ADI-001 in relapsed/refractory NHL patients; future progress of the Phase 1 trial of ADI-001, including ongoing patient enrollment; expectations regarding future regulatory filings for product candidates in the Company's pipeline, including the planned IND submission for ADI-925 in the second half of 2023; timing of a dose selection for the Phase 2 trial by the end of 2022 and initiation of a potentially pivotal program in the first half of 2023, expectations for the in-house manufacturing capabilities in Adicet’s Redwood City facility; and Adicet’s growth as a company and expectations regarding the advancement of its product candidates and expected cash runway. Any forward-looking statements in this presentation are based on management’s current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including without limitation, the effect of COVID-19 on Adicet’s business and financial results, including with respect to disruptions to its clinical trials, business operations, and ability to raise additional capital; Adicet’s ability to execute on its strategy, including obtaining the requisite regulatory approvals on the expected timeline if at all; that positive results, including interim results, from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; clinical studies may fail to demonstrate adequate safety and efficacy of Adicet's product candidates, which would prevent, delay, or limit the scope of regulatory approval and commercialization and regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time-consuming, and inherently unpredictable. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Adicet’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Adicet’s most recent annual report on Form 10-K and subsequent filings with the SEC. All information in this presentation is as of the date its release, and Adicet undertakes no duty to update this information unless 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.
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 Scientific Officer Marco Davila, M.D., Ph.D. Roswell Park Comprehensive Cancer Center Francesco Galimi, M.D., Ph.D. Chief Medical Officer Nick Harvey Chief Financial Officer
Leaders in Developing Allogeneic CAR and CAd γδ T Cell Therapies to Fight Cancer Chen Schor, President and CEO
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 Founded 2015 – 2021 Developed fundamental understanding of γδ T cell biology Optimized robust manufacturing process for allogeneic off-the-shelf γδ1 T cell therapy Built foundational IP portfolio Dec 2021 50% CR rate with ADI-001 in aggressive NHL June 2022 75% CR rate, encouraging preliminary durability, no significant CRS, ICANS or Gr3+ infection rate in aggressive NHL Potential for outpatient dosing November 2022 Four new highly differentiated γδ T cell therapy pipeline programs Building on years of expertise, IP and know-how in γδ T cell biology Now & Future ASH clinical update Initiate at least one potentially pivotal program in H1/2023 IND submission for ADI-925 expected in H2/2023
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; Azameera et. al. ISCT 2022 Single dose protects from repeat tumor challenge (Romero et al. ASGCT 2019) Gamma delta 1 CAR T cells expansion capacity is better than CAR NK cells and comparable or better then alpha-beta CAR T cells (Nishimoto et al) Predominantly activating receptors (Nishimoto, Makkouk, and Azameera et. al. publications) CLINICAL: CRs demonstrated with ADI001 starting at 30M CAR+ cells (flat dose) in bulky tumors > 6,000 mm (ASCO 2022 presentation) Active dose of ADI-001 ~ 1% of NK total dose per lympho-depletion cycle (ASCO 2022 presentation) Gentles et. Al. Nat Med. 2015 Adaptive anti-tumor response Active tumor homing Predominantly activating receptor expression Preclinical persistence by repeat tumor challenge Prognostic value of tumor infiltration Safety* Low GvHD risk CLINICAL: No GvHD and no ≥ grade 3 GvHD cases with ADI-001 (ASCO 2022) Low risk of cytokine release syndrome ≥ grade 3 risk COGS No gene editing required (may affect efficacy) PRE-CLINICAL: No gene editing with ADI-001 Manufacturing for pivotal and commercial with CRO Scalable manufacturing
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 CAR or CAd Adicet’s Pipeline Strategy Hematologic malignancies where Adicet established clinical POC, or Indications where infiltrating γδ T cells correlated with OS, or Indications where donor lymphocyte infusions, enriched with γδ T cells, have shown clinical benefit γδ T cells innate and adaptive anti-tumor activity
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 Solid Tumors ADI-002+ GPC3 HCC Building a Broad Pipeline of First-in-Class CAR and CAd γδ T Cell Product Candidates Partnered programs Adicet wholly owned programs ADI-925 is an engineered Chimeric Adapter (CAd) γδ1 T cell product candidate targeting stress ligands, including MICA/MICB & ULBP1-6, expressed on malignant cells + Regeneron exercised its option to license the exclusive worldwide rights to ADI-002 HCC: Hepatocellular carcinoma; mCRPC: Metastatic castration-resistant prostate cancer; MICA/MICB: Major histocompatibility complex (MHC) Class I chain-related protein A/B; NHL: Non-Hodgkin's lymphoma; PSMA: Prostate-specific membrane antigen; RCC: Renal cell carcinoma; ST: Solid tumor; ULBP: UL16 binding protein
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 the cell This means that one cell therapy product may demonstrate anti-tumor activity in multiple hematologic malignancies and solid tumors without a CAR.
Preclinical Pipeline Overview Blake Aftab, Ph.D. Chief Scientific Officer
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 B7-H6 Multiple Solid / Heme ADI-xxx Undisclosed Multiple Myeloma ADI-xxx Undisclosed Solid Tumors ADI-002+ GPC3 HCC Partnered programs Adicet wholly owned programs ADI-925 is an engineered Chimeric Adapter (CAd) γδ1 T cell product candidate targeting stress ligands, including MICA/MICB & ULBP1-6, expressed on malignant cells
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 malignant cells ADI-925 has demonstrated increased anti-tumor activity at lower concentrations of Vδ1 T cells Developed in-house with broad IP on file CAd γδ T NCRs HLA Independent TCR Natural Targeting of Stress Ligands on Cancer cells NKG2D DAP10mod γδ TCR 4-1BB CD3ζmod DNAM-1 NCRs tEGFR Natural Cytotoxicity Receptors recognize tumor stress antigens tEGFR as a marker to detect CAd+ cells CAd designed to amplify innate and adaptive activation pathways DAP10: Hematopoietic cell signal transducer; DNAM: DNAX accessory molecule; MIC: Major histocompatibility complex class I chain-related protein; mod: Modified domain(s); NCR: natural cytotoxicity receptor; NKG2D: Killer cell lectin like Receptor K1; TCR: T cell receptor; tEGFR: Truncated epidermal growth factor receptor
First-in-class CAd Enhancement of Intrinsic gd T Cell Activity ADI: Adicet Bio, ULBP: UL16-binding protein
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, melanoma, MCC, TNBC, HCC, Cervical, NSCLC, RCC, prostate, colorectal, CLL, bladder cancers and others2,3 Jones et al. Cancers (2022) Zhao et al. Oncotarget (2017) Groh et al. PNAS (1999) CLL: Chronic lymphocytic leukemia; MM: Multiple myeloma; MCC: Merkel cell carcinoma, TNBC: Triple negative breast cancer, NSCLC: Non-small cell lung cancer, RCC: Renal cell carcinoma MICA/MICB staining by immunohistochemistry Expression of ULBP 1, 2, 3, 4, 5, 6 not shown Oncogenic Transformation DNA Damage Cell Cycle Alterations Breast Cancer Lung Cancer RCC Ovarian Cancer Groh et al. PNAS (1999) Normal Breast Normal Kidney
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)
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-CAR Vδ1 T cells CAd+ Vδ1 T cells
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 within tumor tissues Hepatocellular Carcinoma Tumor Model PRESENTED AT SITC 2022 Herrman et. al. SITC (2022) 0
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 capacity within tumor Key challenges Potency of non-engineered cell monotherapy may be limited Lack of approaches to enhance intrinsic gd T cell activity beyond that of correlation Solid tumors may require engineered effector targeting coupled to tumor and tissue specific homing Target validation Presence of gd T cells in tumors correlates with OS3,4,5,6 Many stress antigens selected by evolution to mark malignant cells Unmodified allogeneic gd T cell therapy shows encouraging clinical signal in AML1,2 Orthogonal NKG2D CARs have demonstrated clinical POC7 IND filing expected H2/2023 NCT03533816; Ph1 update 4. Arruda et al. Blood Adv (2019) 7. NCT04623944; Ph1 update NCT03790072; Ph1 update 5. Godder et al. Bone Marrow Trans (2007) Gentles et al. Nat Med (2015) 6. Meraviglia et al. Oncoimmunology (2017)
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 B7-H6 Multiple Solid / Heme ADI-xxx Undisclosed Multiple Myeloma ADI-xxx Undisclosed Solid Tumors ADI-002+ GPC3 HCC Partnered programs Adicet wholly owned programs *ADI-925 is an engineered Chimeric Adapter (CAd) γδ1 T cell product candidate targeting stress ligands, including MICA/MICB & ULBP1-6, expressed on malignant cells
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 with CD27-based CAR (compared to scFv-based CAR)3 Three mechanisms of action designed to address tumor heterogeneity Homing of γδ T cells reported in RCC Inclusion of armoring to address suppressive TME Key challenges Modest responses rates with CD70-targeted agents to-date Agents with limited mechanisms of action do not address tumor heterogeneity No tissue-specific mechanisms for tropism with any agents (ADCs, mAbs, αβ T-cell therapy) Payload-driven toxicities with ADCs Immunosuppressive environment of RCC and other solid tumors Target validation CD70 expression is present in majority of patients with RCC (80%)1 & AML (>96%)2 Including, expression on both leukemic blasts and leukemic stem cells3 Preliminary clinical validation of target in both AML and RCC: Clinical activity observed in AML with CD70-targeted mAb4,5 Single-digit OR and double-digit SD rates with ADCs in RCC (& AML), limited by payload-driven toxicities6,7,8 Disease control seen with unarmored allogeneic αβ T-cell therapy (incl. one CR in advanced RCC patient)8 Adam et al. BJC (2006) 4. Aftimos et al. Clin Cancer Res (2017) 7. Massard et al. Cancer Chemother Pharmacol (2019) Riether et al. JEM (2016) 5. Roboz et al. ASH (2021) 8. CRISPR Therapeutics Presentation (2022) Sauer et a. Blood (2021) 6. Tanner et al. Invest New Drugs (2014)
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 improved serial killing, and resilience against suppressive factors Supports functional enhancement illustrated in preclinical models Complimentary Natural Cytotoxicity Receptors HLA Independent TCR Natural Targeting of Stress Ligands on Cancer cells CAR-Directed Killing using CD27 ligand NCRs NKG2D DNAM-1 NCRs TGFb-DNR TGFb Dominant Negative Receptor armors against immunosuppressive TME CD27-derived CAR CD27 Sauer et al. Blood (2021) Junker et al. Cytokine (2000)
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 High Efficiency Production of CD70 CAR with Resulting Phenotype Consistent to ADI-001 Nishimoto et. al. Clin Trans Immunol (2022) PRESENTED AT SITC 2022 Lamture et. al. SITC (2022)
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 Carcinoma (x3), and Cervical Carcinoma shown Anti-Tumor Cytotoxicity at Low E:T Ratio CD70 Antigen Density PRESENTED AT SITC 2022 Lamture et. al. SITC (2022)
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 immunotherapies2 and CAR T3 Armoring aims to preserve T cell function in the presence of immunosuppressive factors like TGFb Batlle & Massagué. Immunity (2019) Silk et al. Immunology (2022) Zhang et al. Front Cell Dev Biol (2021) PRESENTED AT SITC 2022 TGFβ alters effector activation profile Genes up-regulated in TGF-β1 treated conditions Genes down-regulated in TGF-β1 treated conditions Lamture et. al. SITC (2022) CXCR4 T-bet
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
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
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 Challenge 2 Challenge 1 Challenge 1 Challenge 2 Lamture et. al. SITC (2022) CD70 CAR
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 T cells PRESENTED AT SITC 2022 NSG Mouse Lamture et. al. SITC (2022)
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 1. Sauer et al. Blood (2021) Opportunity for Adicet and γδ T cells Response to low antigen density by design with CD27-based CAR (compared to scFv-based CAR)3 Three mechanisms of action designed to address tumor heterogeneity Homing of γδ T cells documented in RCC and improved AML OS Inclusion of armoring to address suppressive TME
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 B7-H6 Multiple Solid / Heme ADI-xxx Undisclosed Multiple Myeloma ADI-xxx Undisclosed Solid Tumors ADI-002+ GPC3 HCC Partnered programs Adicet wholly owned programs *ADI-925 is an engineered Chimeric Adapter (CAd) γδ1 T cell product candidate targeting stress ligands, including MICA/MICB & ULBP1-6, expressed on malignant cells
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 suppressive TME No significant CRS and ICANS demonstrated with Adicet CAR γδ T cells in clinical trials reported to-date; potential to address therapeutic index Key challenges Limited therapeutic index due to CRS, ICANS, and macrophage activation syndrome with PSMA targeted T cell engagers and alpha-beta CAR T cell approaches4,6 Single mechanism of targeting limits activity in heterogeneous tumors Immunosuppressive environment of mCRPC associated with TGFb7 Target validation PSMA expression is present in >85% of patients with mCRPC1 with limited expression in normal tissues (100-1,000 times overexpressed) Clinically validated via multiple modalities: PSMA targeted radiotherapy approved for mCRPC2 Immunotherapies (T-cell engaging antibodies and cell therapies) demonstrated PSA, PSMA-radiographic, and RECIST responses in early clinical studies3,4,5 Adam et al. BJC (2006) 4. Tran et al. Ann Onc. (2020) 7. Mirazaei et al. Int J Biol Macromol (2022) Sartor et al. N Eng J Med (2021) 5. Slovin et al. JCO supp (2022) De Bono et al. JCO supp (2021) 6. Narayan et al. Nat Med (2022) mCRPC: metastatic castrate-resistant prostate cancer; PSMA: Prostate-specific membrane antigen; RECIST: Response Evaluation Criteria in Solid Tumors
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 Natural Targeting of Stress Ligands on Cancer cells CAR-Directed Killing NCRs NKG2D DNAM-1 NCRs TGFb-DNR TGFb Dominant Negative Receptor armors against immunosuppressive TME Liu et al. Cancer Res. (1997)
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 target-associated proliferation Improved cytotoxicity over benchmark1 Improved in vivo activity over benchmark1 22Rv1 (hetero) PC3-PSMA 22Rv1 (hetero) PC3-PSMA No target Untransduced Ctrl PSMA Vδ1 CAR Lead J591 Control CAR Proliferation NFAT: Nuclear factor of activated T-cells PRESENTED AT SITC 2022 Liu et al. Cancer Res. (1997) Ramadoss et. al. SITC 2022
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)
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 (hetero) PRESENTED AT SITC 2022 Ramadoss et. al. SITC (2022) Control 22Rv1 Tumors Express Intermediate and Heterogeneous PSMA
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 B7-H6 Multiple Solid / Heme ADI-xxx Undisclosed Multiple Myeloma ADI-xxx Undisclosed Solid Tumors ADI-002+ GPC3 HCC Partnered programs Adicet wholly owned programs *ADI-925 is an engineered Chimeric Adapter (CAd) γδ1 T cell product candidate targeting stress ligands, including MICA/MICB & ULBP1-6, expressed on malignant cells
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 and colorectal tissues Three mechanisms for anti-tumor activity (CAR, innate, and adaptive immunity) designed to address tumor heterogeneity Key challenges Susceptibility to inhibition by shed antigen Selective and specific antigen targeting Single MOA overcome by heterogeneous antigen expression in solid tumors Limited intratumoral homing and proliferation Immunosuppressive TME Target validation B7-H6 is expressed in >95% of CRC cases, and other gastrointestinal cancers, with limited expression in normal tissues1 Well established biological role in natural tumor surveillance and active clinical development1 Preclinical activity with bispecific T-cell engaging antibodies2 and NKp30 related CAR T3 In vivo activity with B7-H6 targeted therapies against both hematological and solid tumor indications2,3,4 NCT04752215 Zhang et al. Clin Can Res (2022) Zhang et al J Immunol (2012) Brandt et al J exp Med (2009) CRC: Colorectal cancer; GI: Gastrointestinal; MOA: Mechanism of action
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 Receptors HLA Independent TCR Natural Targeting of Stress Ligands on Cancer cells CAR-Directed Killing NCRs NKG2D DNAM-1 NCRs TGFb-DNR (± other armor) Armor against immunosuppressive TME Hua et al. Protein Eng Des Sel. (2017)
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 Anti-Tumor Cytotoxicity B7-H6 Antigen Density Resilience to Inhibition by Shed B7-H6 Antigen PRESENTED AT SITC 2022 Hua et al. Protein Eng Des Sel. (2017) Lamture et. al. SITC (2022) BM: Benchmark
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 Hua et al. Protein Eng Des Sel. (2017) PRESENTED AT SITC 2022 Lamture et. al. SITC (2022) Tumor Volume on Day 29 Polyfunctional Strength Index (PSI) Key: Effector Regulatory Stimulatory Inflammatory Chemoattractive NSG Mouse
Summary of Pipeline and 2022 SITC Data Blake Aftab, Ph.D. Chief Scientific Officer
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 Solid Tumors ADI-002+ GPC3 HCC Building a Broad Pipeline of First-in-Class CAR and CAd γδ T Cell Product Candidates Partnered programs Adicet wholly owned programs *ADI-925 is an engineered Chimeric Adapter (CAd) γδ1 T cell product candidate targeting stress ligands, including MICA/MICB & ULBP1-6, expressed on malignant cells
Marco Davila, M.D., Ph.D. Roswell Park Comprehensive Cancer Center Perspectives: Adicet γδ T Cell Pipeline
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 programs offer?
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 preliminary thoughts on the pipeline we have compiled here? What do these engineered γδ1 T cell programs offer?
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? Question 2: Can you share your thoughts on ADI-925 and the chimeric adaptor technology? Question 1: Can you share your preliminary thoughts on the pipeline we have compiled here? What do these engineered γδ1 T cell programs offer?
Closing Remarks Chen Schor, President and CEO
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
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 Report CD20 bispecifics in 4L DLBCL patients post autologous CAR T Glofitamab ASCO (2022), Epcoritamab EHA (2022), GMAB PR June 11 (2022) * CR rate durability for post-CAR T bispecifics modeled as durability of 3L+ autologous CAR-T (for modeling purpose only) MONTH CRS ICANS Frequency Grade3+ CRS Grade 3 ICANS High CRS ICANS Medium CRS ICANS None/Low CRS ICANS 3L= Third line; 4L= Fourth line
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) December 28; 377(26): 2531–2544. J Clin Oncol 38:3095-3106. Yescarta EPAR Public Assessment Report CD20 bispecifics in 4L DLBCL patients post autologous CAR T Glofitamab ASCO (2022), Epcoritamab EHA (2022), GMAB PR June 11 (2022) * CR rate durability for post-CAR T bispecifics modeled as durability of 3L+ autologous CAR-T (for modeling purpose only) MONTH CRS ICANS CRS ICANS ~20%* Frequency Grade3+ CRS Grade 3 ICANS High CRS ICANS Medium CRS ICANS None/Low CRS ICANS
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 Agency; FDA: U.S. Food and Drug Administration; MAA: Marketing Authorization Application; R/R= Relapsed/refractory ADI-001 – Expansion Discuss with the FDA and EMA the design of two potentially pivotal studies and a path to support BLA and MAA submissions Initiate a potentially pivotal program in H1/2023 Initiate additional expansion cohorts in 2023 Pipeline and Manufacturing ADI-925: IND submission expected H2/2023 One new IND planned every 12-18 months Leverage in-house GMP manufacturing to support expanding clinical pipeline Corporate Well financed into H1/2025 with $282M cash and cash equivalents (as of 9/30/22)
Q&A
Leaders in Developing Allogeneic CAR and CAd γδ T Cell Therapies to Fight Cancer