Adicet Bio, Inc. · NASDAQ:ACET
Adicet Bio — 27th ASGCT Annual Meeting 2024
16 slides from Adicet Bio's conference presentation, 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 Shon Green, PhD VP, Nonclinical Development 27th ASGCT Annual Meeting 2024 Baltimore, MD
Slide 2: ADI-270: Designed to address multiple refractory cancers
ADI-270: Designed to address multiple refractory cancers o CAR utilizes CD27 as the binding domain and contains CD27 and 4-1BB costimulatory domains plus CD3ζ (3rd gen) o Inactive form of TGFβ receptor II to mitigate the immunosuppressive effects of TGFβ within the tumor microenvironment o Host vs g
Slide 3: CD70 is expressed on multiple solid and hematological cancers with limited expression in normal tissues
CD70 is expressed on multiple solid and hematological cancers with limited expression in normal tissues o High expression in multiple solid and heme malignancies Representative images from a normal tissue array stained for CD70 ▪ Beyond ccRCC and NPC, multiple solid tumors are of interest when Ovary
Slide 4: ADI-270 is highly pure for Vδ1 T cells and expresses memory markers
ADI-270 highly enriched for V1 and memory phenotype Donor Selective aß T Cell Final Leukapheresis Activation of Transduction Expansion Depletion Formulation Vδ1 T Cells Activation with proprietary Ab for Vδ1 expansion ADI-270 expresses T cell memory markers, innate and chemokine ADI-270 ADI-270fina
Slide 5: ADI-270 is resilient to the inhibitory effects of TGFβ
ADI-270 is resilient to the inhibitory effects of TGFβ ADI-270 is ADI-270 resilient showed to transcriptional resilience to transcriptional ADI-270 ADI-270 maintains maintained cytotoxicity cytotoxicity in in the changes driven by TGFβ signaling the presence presence of TGFꞵ1 of TGF changes driven
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 ADI-270persisted ADI-270 persists in in culture culture with with primed primed alloreactiveTTcells alloreactive cellsderived derivedfrom from33donors donors (compared to target alone) 15
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 CD70 expression Tumor cell lines CD70 CD70 Ag Agdensity 100 density CD70 molecules per cell % cytotoxicity +/- SD 120000 A498 80 Caki-2 100000 769-P 60 THP-1 80000 20000 HUT-
Slide 8: ADI-270 retained potent activity in the context of CD70-low tumors
ADI-270 retained potent activity in the context of CD70-low tumors compared to clinically relevant CD70-targeting αβ CAR T cell benchmarks A498 (CD70 high) ACHN (CD70 low) Normal Normalcells cells 100 100 ACHN (CD70 low) 100 100 % cytotoxicity +/- SD % cytotoxicity +/- SD ADI-270 % cytotoxicity +/-
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 100 % cytotoxicity +/- SD A498 tumors and 80 ✱✱✱✱ CD70 KO A498 60 40 ADI-270 CD70- 20 tumor only +/- ADI-270 CD70 0 tumor mixture CAR T cell Ag 0 12 24 36 48 activation post-stimulation (h
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 CD70 KO A498 tumors % cytotoxicity +/- SD 100 ADI-270 CAR-T Ref 1 80 CAR-T Ref 2 αβ CAR T ADI-270 references 60 40 **** 20 *** 0 0 :1 1 :2 1 :1 2 :1 Higher killing Lower killing
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 Macrophages + CD70+ Tumor cells + CAR T cells A498 tumors + 10000 10000 10000 10000 50000 macrophages pg/mL/1e6 cells ± SD 8000 8000 8000 8000 40000 6000 6000 6000 6000 30000 400
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 Normal cells + CD70+ Tumor cells + CAR T cells 600 500 HUVEC cell count per image (+/-SD) A498 tumors + HUVEC cells 400 ✱✱✱✱ ✱✱✱✱ 300 200 ADI-270 CAR T cell 100 αβ CAR-T Ref 1
Slide 13: A single dose of ADI-270 showed potent regression and sustained anti-tumor activity in ccRCC
A single dose of ADI-270 showed potent regression and sustained systemic anti-tumor activity in ccRCC 3000 xenograft models Mean Tumor Volume (mm3) +/- SEM 2500 Opposite Flank Tumor Rechallenge D18 post initial treatment Small tumor Medium 2000tumor ~100mm3 ~500mm3 ✱✱✱✱ 1500 Tumor regression Rechall
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 A single A single dose dose of ADI-270 of ADI-270 showspotent showed potent efficacy efficacy in in A498 A498 tumors, tumors,rapidly rapidlyeradicating eradicatingCD70+ CD
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 A single dose of ADI-270 was administered IV into NSG mice harboring SC tumor xenografts Adicet Bio internal data 15
Slide 16: Next steps: ADI-270
Next steps: ADI-270 o ADI-270 represents potential evolution of γδ CAR T-cell based therapeutics o CD27-based 3rd gen CAR demonstrated significant potency advantages1,2,3,4 o Armoring against TGFβ and alloreactive T cells confirmed and characterized preclinically o Robust efficacy maintained across