Slide 1: Vispa-cel, an allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout, in r/r B-NHL
Vispa-cel, an allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout, in patients with relapsed/refractory B cell non-Hodgkin lymphoma Long-term follow-up results from the ANTLER phase 1 trial Stephen J. Schuster, Houston Holmes, James Essell, Ayad Hamdan, Boyu Hu, Elizabeth Brem, Rushang Pate
Slide 2: Disclosures
Disclosures Advisory board for AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Caribou, Genentech/Roche, Genmab, Janssen, Novartis, and Vittoria Bio Consultant for AstraZeneca, BioNTech, Caribou, Genmab, Incyte, and Novartis Research support from AstraZeneca, BMS, Genentech/Roche, Genmab, and N
Slide 3: Most 2L LBCL patients do not receive treatment with curative intent
Most 2L LBCL patients do not receive treatment with curative intent No time to wait due to rapid disease 75% progression or CAR-T manufacturing failure Geographic, financial, socioeconomic, or of 2L LBCL patients insurance issues impact CAR-T accessibility do not receive autologous CAR-T cell therap
Slide 4: Vispa-cel: a differentiated allogeneic CAR-T cell therapy for 2L LBCL
Vispa-cel: a differentiated allogeneic CAR-T cell therapy for 2L LBCL PD-1 knockout Optimized vispa-cel includes: Enhances T cell fitness and • Young donor age (<30 years old) antitumor activity 1,2 • HLA matched to ≥2 alleles Single infusion of optimized vispa-cel Vispa-cel demonstrates efficacy, s
Slide 5: 85 patients dosed with vispa-cel in ANTLER trial
85 patients dosed with vispa-cel in ANTLER trial Eligibility • Dose escalation: third- or later-line or primary refractory aggressive r/r B-NHL1 Vispa-cel dose levels evaluated • Dose expansion: second-line LBCL 2 (primary refractory disease or • 40, 80, and 120x10 6 CAR-T cells relapse ≤12 months a
Slide 6: ANTLER subgroups
ANTLER subgroups R/R B-NHL Total treated 40M, 80M, 120M CAR-T cells N=85 Optimized vispa-cel 2L and 3L+ LBCL N=35 40M, 80M, 120M CAR-T cells Young donor (<30 yo) 2+ HLA matching 2L LBCL 80M CAR-T cells Pivotal optimized vispa-cel Young donor (<30 yo) N=27 2+ HLA matching This subgroup best represent
Slide 7: Patient and disease characteristics in ANTLER (N=85)
Patient and disease characteristics in ANTLER (N=85) All treated patients Optimized vispa-cel1 Pivotal optimized vispa-cel2 Baseline characteristics (All patients) (2L LBCL, RP2D) N=85 N=35 N=27 Age, years, median (range) 66 (20-86) 63 (20-86) 66 (20-86) Age ≥ 65 years, n (%) 45 (53) 17 (49) 14 (52)
Slide 8: Optimized vispa-cel delivered durable, long-term efficacy in ANTLER
Optimized vispa-cel delivered durable, long-term efficacy in ANTLER 100 100 80 100 Progression-free survival Optimized vispa-cel1 Pivotal optimized vispa-cel2 (All patients) (2L LBCL, RP2D) (%) Rate (%) 80 60 80 N=35 N=27 50 ORR 83% 82% Survival Median PFS = 17.1 mo Survival rate (%) 60 40 60 CR rat
Slide 9: Single 80M dose of pivotal optimized vispa-cel drives long-term, potentially curative responses
Single 80M dose of pivotal optimized vispa-cel in 2L LBCL patients drives long-term, potentially curative responses Pt ID HLA 008-104 2 1 013-002 3 2 016-002 3 3 034-001 5 4 204-001 2 5 202-003 9 6 202-007 5 7 Pivotal optimized vispa-cel 035-007 5 8 035-005 2 9 (N=27) 1 025-005 7 10 026-003 5 11 ORR
Slide 10: Vispa-cel has a generally well-tolerated safety profile
Vispa-cel has a generally well-tolerated safety profile Enables outpatient administration and further expansion to community sites Vispa-cel All treated patients Optimized vispa-cel Pivotal optimized vispa-cel N=85 (All patients) (2L LBCL, RP2D) N=351 N=272 All grade ≥Gr 3 All grade ≥Gr 3 All grade
Slide 11: Rapid hematologic and immunologic recovery after vispa-cel
Rapid hematologic and immunologic recovery after vispa-cel contributes to generally well-tolerated safety profile B cell, T cell, and NK cell depletion Absolute neutrophil and platelet count and recovery to baseline levels in optimized cohort recovery to Grade ≤2 1.0 T cells 0.8 Probability of recov
Slide 12: CAR-T cell expansion and functional persistence correlate with duration of response and HLA match level
CAR-T cell expansion and functional persistence correlate with duration of response and HLA match level All patients who received optimized vispa-cel HLA match level (<2 vs ≥2) impact on PK for N=351 vispa-cel manufactured from young donor T cells N=54 Response ≥3 months HLA match ≥ 2 (N=35) Progres
Slide 13: Next steps for vispa-cel in 2L LBCL
Next steps for vispa-cel in 2L LBCL • Vispa-cel is a potential paradigm shift towards an off-the-shelf, scalable, CAR-T approach in 2L LBCL patients that achieves durable remissions • Vispa-cel can overcome the logistical barriers of auto CAR-T and the need for continuous infusions of bispecific ant
Slide 14: ANTLER-3: phase 3 randomized pivotal trial design
ANTLER-3: phase 3 randomized pivotal trial design Inclusion criteria: Investigator’s choice of SOC regimens3 with 1:1 randomization • 2L LBCL1 crossover to vispa-cel Primary endpoint: Screening • CD19-naïve PFS, interim analysis 5 planned permitted after PD N~250 • Relapse (early or late) or refract
Slide 15: ANTLER phase 1 trial conclusions
ANTLER phase 1 trial conclusions • Vispa-cel is a differentiated allogeneic CAR-T cell therapy ✓ PD-1 knockout potentially contributes to enhanced antitumor activity ✓ Donor age and partial HLA matching improve clinical outcomes • Long-term durable remissions demonstrated after a single infusion of
Slide 16: Gratitude for our patients, caregivers, investigators, and site staff
Gratitude for our patients, caregivers, investigators, and site staff ANTLER trial sites in US OHSU Tufts Israel - ANTLER NYU Langone Hadassah University Hospital MCW Montefiore Rabin Medical Center Hackensack Tel Aviv Sourasky Medical Center Univ of Atlantic Health The Sheba Fund for Health Service