Autolus Therapeutics Plc · NASDAQ:AUTL
Autolus Therapeutics — ASH 2023
17 slides from Autolus Therapeutics's conference presentation, December 2023
Slide 1: Obecabtagene autoleucel for R/R adult B-ALL: pooled analysis of FELIX Phase Ib/II
Publication Number: 222 OBECABTAGENE AUTOLEUCEL (OBE-CEL, AUTO1) FOR RELAPSED/REFRACTORY ADULT B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (R/R B-ALL): POOLED ANALYSIS OF THE ONGOING FELIX PHASE IB/II STUDY Claire Roddie,1 Karamjeet S. Sandhu,2 Eleni Tholouli,3 Paul Shaughnessy,4 Pere Barba,5 Manuel Guerrei
Slide 2: Background
Background 2 • Obecabtagene autoleucel (obe-cel) is an autologous CAR-T cell product, which utilizes a fast off-rate CD19 binder to reduce toxicity and improve persistence1,2 • The clinical activity of obe-cel has been evaluated in Phase I studies in R/R pediatric1 and adult B-ALL,2 and other B-cell
Slide 3: FELIX: obe-cel tested in adults with R/R B-ALL
FELIX: obe-cel tested in adults with R/R B-ALL 3 Study design with leukemic burden-adjusted split dosing Obe-cel manufacturing Leukapheresis Split dose infusion Day –6 Day 1 Day 10 Bridging therapy Efficacy and safety follow-up BMA BMA Day -6 Screening Enrollment Lymphodepletion Flu 30 mg/m2 Cy 500
Slide 4: FELIX: patient eligibility and endpoints
FELIX: patient eligibility and endpoints 4 Key eligibility criteria Cohort A Cohort B Cohort C ≥5% BM blasts MRD-positive Isolated EMD • R/R adult B-ALL* at screening at screening at screening • Age ≥18 years Selected endpoints‡ • CR/CRi rate per IRRC • MRD-negativity rate(<10–4) • DoR • Safety • EF
Slide 5: FELIX: patient disposition
FELIX: patient disposition 5 127/153 (83%) enrolled patients received obe-cel* n (%) Discontinued Enrolled‡ 26 (17) N = 153 Death 15 (10) Data cut-off date: Manufacturing-related 7 (5) September 13, 2023 Adverse event 2 (1) Infused N = 127 (83%) Physician decision 1 (0.7) Progressive disease 1 (0.7)
Slide 6: FELIX: baseline characteristics
FELIX: baseline characteristics 6 Heavily pre-treated patients (many post-allogeneic SCT) All treated patients (N = 127) n (%)* Median age, years (range) 47 (20–81) Male/female 66/61 (52/48) Asian 16 (13) Black or African American 2 (2) White 94 (74) Unknown 15 (12) Hispanic or Latino 38 (30) Philad
Slide 7: Obe-cel manufacturing
FELIX: obe-cel manufacturing 7 Robust and rapid manufacturing, despite variable starting material Starting material quality Release parameters Vein-to-release time 100 100 100 50 90 90 90 45 80 80 80 40 Viability on thaw (%) Transduction (%) 70 70 70 35 CD3+ cells (%) 60 60 60 30 Days 50 50 50 25 40
Slide 8: FELIX: remission rate and MRD by status at lymphodepletion
FELIX: remission rate and MRD by status at lymphodepletion 8 High MRD-negative remission rates were observed after obe-cel Morphologic disease* (n = 98) • 74% of patients had CR/CRi (n = 73) • 95% of evaluated responders were MRD-negative‡ All treated patients (N = 127) No morphologic disease (n = 2
Slide 9: FELIX: CR/CRi subgroup analysis per IRRC
FELIX: CR/CRi subgroup analysis per IRRC 9 Obe-cel demonstrated high CR/CRi rates across all subgroups Total, ORR, ‡ Subgroup n (%) % (95% CI) * Overall 127 (100) 78 (70, 85) Age, years 18–39 48 (38) 63 (47, 76) 40–64 54 (43) 83 (71, 92) ≥65 25 (20) 96 (80, 100) Hispanic or Latino Yes 38 (30) 66 (49
Slide 10: EFS in all treated patients
FELIX: EFS in all treated patients* 10 The event-free survival estimate at 12 months was 50% 100 90 Overall (N = 127) All treated patients 80 (N = 127) 70 Median EFS 11.7 (95% CI), Probability (%) 60 (7.2, NE) months 50 6-month EFS 65 40 (95% CI), % (56, 73) 30 20 Events, n: 12-month EFS 50 Overall
Slide 11: Obe-cel persistence in responders
FELIX: obe-cel persistence in responders 11 Obe-cel has high expansion and long-term persistence All treated 100,000 patients (N = 127) Copies/ug DNA (PB) 10,000 Cmax, copies/ug 110,896 Geo-Mean, CV% (254) 1000 Tmax, days 14 Median, range (2–55) 100 AUC0–28d, copies/ug×d 1,105,176 Geo-Mean, CV% (212
Slide 12: FELIX: leukemic burden in all treated patients
FELIX: leukemic burden in all treated patients 12 Leukemic burden at screening is not predictive of leukemic burden prior to lymphodepletion 118/127 (93%) patients received BM blasts % bridging therapy* BM blasts % prior at screening to lymphodepletion 16% 16% <5% 28% 28% <5% ≥5−≤75% 53% 53% ≥5−≤75%
Slide 13: EFS by leukemic burden prior to lymphodepletion
FELIX: EFS by leukemic burden prior to lymphodepletion* 13 Lower leukemic burden is associated with better outcomes <5% (n = 36) 100 ≥5−≤75% (n = 51) 90 >75% (n = 40) 80 70 Probability (%) 60 50 40 Events, n: <5% 10 30 ≥5−≤75% 22 >75% 27 20 Median (95% CI): 10 <5% NE ≥5−≤75% 15 (6.6, NE) 0 >75% 4.5
Slide 14: CRS and ICANS
FELIX: CRS and ICANS Low rates of Grade ≥3 CRS and/or ICANS were observed CRS and ICANS CRS by ICANS by in all patients % BM blasts % BM blasts 100 100 100 88% 80 80 80 69% 69% Incidence, % Incidence, % Incidence, % 60 60 60 47% 43% 40 40 40 23% 20 20 20 18% 3% 8% 0% 6% 15% 2% 7% 0% 4% 0 0 0 CRS ICA
Slide 15: FELIX: TEAEs
FELIX: TEAEs Favorable safety profile All treated patients (N = 127) TEAEs that occurred in ≥20% of patients regardless of causality Any grade, % Grade ≥3, % Patients with any TEAE 100 81 CRS 69 2 Pyrexia 29 2 Nausea 26 2 Diarrhea 25 2 Febrile neutropenia 24 24 Anemia 24 21 Headache 24 0 Neutropenia
Slide 16: FELIX: Phase Ib/II conclusions
FELIX: Phase Ib/II conclusions 16 • Obe-cel successfully manufactured in 95% of leukapheresed patients • High remission rates independent of leukemic burden at lymphodepletion • 50% EFS estimate at 12 months, with only 17% of responders proceeding to SCT while in remission • Favorable safety profile
Slide 17: Acknowledgments
Acknowledgments 17 • The authors would like to acknowledge: − Patients, families, friends, and caregivers − Study investigators and coordinators − Healthcare staff at the study sites − Autolus Therapeutics Teams Contact: Dr Claire Roddie c.roddie@ucl.ac.uk