Adicet Bio, Inc. · NASDAQ:ACET
Adicet Bio — 27th ASGCT Annual Meeting 2024
16 slides from Adicet Bio's conference presentation, May 10, 2024
Slide 1: ADI-270: An Armored Allogeneic Anti-CD70 CAR γδ T cell Therapy Candidate
ADI-270: An Armored Allogeneic Anti-CD70 CAR γδ T cell Therapy Candidate Designed for Multiple Solid and Hematological Cancer Indications 27th ASGCT Annual Meeting 2024 Baltimore, MD Shon Green, PhD VP, Nonclinical Development
Slide 2: ADI-270: Designed to address multiple refractory cancers
ADI-270: Designed to address multiple refractory cancers CAR utilizes CD27 as the binding domain and contains CD27 and 4-1BB costimulatory domains plus CD3ζ (3rd gen) Inactive form of TGFβ receptor II to mitigate the immunosuppressive effects of TGFβ within the tumor microenvironment Host vs graft a
Slide 3: CD70 is expressed on multiple solid and hematological cancers with limited normal tissue expression
High expression in multiple solid and heme malignancies Beyond ccRCC and NPC, multiple solid tumors are of interest when paired with CD70 screening Minimal expression on normal tissues (activated lymphocytes) Target has clinical safety experience CD70 is expressed on multiple solid and hematological
Slide 4: ADI-270 is highly pure for Vd1 T cells
ADI-270 highly enriched for Vd1 and memory phenotype % cells positive D o n o r L e u k a p h e r e s i s T r a n s d u c t i o n E x p a n s i o n a ß T C e l l D e p l e t i o n F i n a l F o r m u l a t i o n S e l e c t i v e A c t i v a t i o n o f V δ 1 T C e l l s Adicet Bio internal data ADI
Slide 5: ADI-270 is resilient to the inhibitory effects of TGFβ
ADI-270 is resilient to the inhibitory effects of TGFβ Adicet Bio internal data ADI-270 showed resilience to transcriptional changes driven by TGFb signaling ADI-270 maintained proliferation in the presence of TGFb ADI-270 maintained cytotoxicity in the presence of TGFb
Slide 6: CD70-targeting armors ADI-270 against alloreactive host T cells
CD70-targeting armors ADI-270 against alloreactive host T cells Proposed MoA for enhanced persistence of ADI-270 Host Adicet Bio internal data test materials from same donor PBMCs ADI-270 persisted in culture with primed alloreactive T cells derived from 3 donors
Slide 7: ADI-270 exhibited potent in vitro cytotoxicity against a range of CD70 levels
ADI-270 exhibited potent in vitro cytotoxicity against a range of CD70 levels in a diverse set of solid and heme malignancies Adicet Bio internal data CD70 Ag density E:T ratio = 1:1
Slide 8: ADI-270 retained potent activity in CD70-low tumors compared to benchmarks
ADI-270 retained potent activity in the context of CD70-low tumors compared to clinically relevant CD70-targeting αβ CAR T cell benchmarks Adicet Bio internal data
Slide 9: ADI-270 contributed CAR-dependent and CAR-independent mechanisms of tumor targeting
ADI-270 contributed CAR-dependent and CAR-independent mechanisms of tumor targeting CD70+/- tumor mixture model Increased killing of CD70neg tumors within tumor mixture CAR T cell Ag activation A498 tumors and CD70 KO A498 E:T ratio = 1:1, N=2 donors, ****p<0.0001 Adicet Bio internal data test mater
Slide 10: ADI-270 demonstrated higher innate cytolytic activity against CD70 negative tumor cells
ADI-270 demonstrated higher innate cytolytic activity against CD70 negative tumor cells compared to CAR-T cell references ***p<0.001, ****p<0.0001 CD70 KO A498 tumors ADI-270 αβ CAR T references Higher killing Lower killing Adicet Bio internal data test materials derived from same donor PBMCs
Slide 11: ADI-270 associated with lower potential for macrophage activation syndrome and CRS
ADI-270 associated with a lower potential for macrophage activation syndrome and CRS compared to αβ CAR T cell benchmarks Lower inflammatory profile Higher inflammatory profile CAR T cell activation A498 tumors + macrophages ADI-270 αβ CAR T Benchmarks Adicet Bio internal data
Slide 12: ADI-270 did not demonstrate activation-induced off-target toxicity
ADI-270 did not demonstrate activation-induced off-target toxicity compared to clinically relevant αβ CAR T cell benchmarks Maintained endothelial growth Reduced endothelial growth CAR T cell activation A498 tumors + HUVEC cells ADI-270 αβ CAR T Benchmarks Adicet Bio internal data
Slide 13: A single dose of ADI-270 showed potent regression in ccRCC xenograft models
A single dose of ADI-270 showed potent regression and sustained systemic anti-tumor activity in ccRCC xenograft models ADI-270 (5, 10, or 15 x 106 I.V.) ADI-270 (5 or 10 x 106 I.V.) Small tumor ~100mm3 Medium tumor ~500mm3 Monitor tumor volume Monitor tumor volume Monitor tumor volume ****p<0.0001 T
Slide 14: ADI-270 demonstrated rapid homing, activation and killing kinetics in ccRCC xenografts
ADI-270 demonstrated rapid homing, activation and killing kinetics in ccRCC xenografts resulting in tumor and target eradication Adicet Bio internal data A single dose of ADI-270 showed potent efficacy in A498 tumors, rapidly eradicating CD70+ cells ADI-270 infiltrated and proliferated with effector
Slide 15: ADI-270 anti-tumor activity extended to multiple hematologic tumor xenografts
ADI-270 anti-tumor activity extended to multiple hematologic tumor xenografts associated with lower CD70 expression Adicet Bio internal data A single dose of ADI-270 was administered IV into NSG mice harboring SC tumor xenografts
Slide 16: Next steps: ADI-270
Next steps: ADI-270 ADI-270 represents potential evolution of γδ CAR T-cell based therapeutics CD27-based 3rd gen CAR demonstrated significant potency advantages1,2,3,4 Armoring against TGFβ and alloreactive T cells confirmed and characterized preclinically Robust efficacy maintained across multiple