Autolus Therapeutics Plc · NASDAQ:AUTL
Autolus Therapeutics — ASH Analyst Meeting and Webcast 2023
42 slides from Autolus Therapeutics's conference presentation, Dec 11, 2023
Slide 1: Developing Next Generation Programmed T Cell Therapies
Developing Next Generation Programmed T Cell Therapies ASH Analyst Meeting and Webcast December 2023
Slide 2: Disclaimer
Disclaimer 2Developing Next Generation Programmed T Cell Therapies These slides contain forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and
Slide 3: Agenda
Agenda • Welcome and Introduction: Rob Dolski, CFO • Opening Remarks: Dr. Christian Itin, CEO • FELIX pooled analysis in B-ALL: Dr. Claire Roddie, Associate Professor Haematology and Honorary Consultant Haematologist, Cancer Institute, University College London • Building the obe-cel Opportunity and
Slide 4: Building a leading CAR T company developing transformational therapies for cancer and autoimmune diseases
Building a leading CAR T company developing transformational therapies for cancer and autoimmune diseases • Clinical data updates at 2023 American Society of Hematology (ASH) – Obe-cel: oral presentation – pooled analysis of the ongoing FELIX Phase Ib/II study – Obe-cel: poster presentation – pooled
Slide 5: Reminder of obe-cel's unique mechanism of action
Reminder of obe-cel’s unique mechanism of action • Avoids over-activation of CAR T cells • Increases CAR T peak expansion • Avoids exhaustion of CAR T-cells 5 Enhanced cytotoxicity and proliferation Off Rate: Kd [S-1] ]1-S1 - [M a K: e Ra t - On Other CD19 Binders Obe-cel Binder Off Rate: Kd [S-1] O
Slide 6: FELIX pooled analysis ASH 2023
FELIX pooled analysis ASH 2023 Dr. Claire Roddie, Associate Professor Haematology and Honorary Consultant Haematologist, Cancer Institute, University College London
Slide 7: Obecabtagene autoleucel for R/R adult B-ALL: pooled analysis of FELIX Phase Ib/II
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 Guerreiro,6 Michael R. Bishop,7
Slide 8: Background
Background • 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 m
Slide 9: FELIX: obe-cel tested in adults with R/R B-ALL
FELIX: obe-cel tested in adults with R/R B-ALL Study design with leukemic burden-adjusted split dosing 9 Screening Leukapheresis Split dose infusion Day 1 Day 10 Enrollment Bridging therapy Efficacy and safety follow-up Cy 500 mg/m2 Lymphodepletion Flu 30 mg/m2 Leukemia burden-adjusted split dosing
Slide 10: FELIX: patient eligibility and endpoints
FELIX: patient eligibility and endpoints 10 *R/R B-ALL: primary refractory; first relapse if first remission ≤12 months; R/R disease after ≥2 lines of systemic therapy; R/R disease after allogeneic transplant; R/R Philadelphia chromosome-positive ALL if intolerant to/failed two lines of any TKI or o
Slide 11: FELIX: patient disposition
FELIX: patient disposition 127/153 (83%) enrolled patients received obe-cel* 11 *Seven patients received Dose 1 only ‡All eligibility criteria met and the leukapheresate accepted for manufacturing obe-cel, obecabtagene autoleucel Data cut-off date: September 13, 2023 Infused N = 127 (83%) Enrolled‡
Slide 12: FELIX: baseline characteristics
FELIX: baseline characteristics Heavily pre-treated patients (many post-allogeneic SCT) 12 All treated patients (N = 127) n (%)* Median age, years (range) 47 (20–81) Male/female 66/61 (52/48) Asian Black or African American White Unknown Hispanic or Latino 16 (13) 2 (2) 94 (74) 15 (12) 38 (30) Phila
Slide 13: FELIX: obe-cel manufacturing
FELIX: obe-cel manufacturing Robust and rapid manufacturing, despite variable starting material • Obe-cel was released for 95% of patients, with a median time from vein-to-release of 22 days • Consistent manufacturing was observed, despite leukapheresis from patients with multiple lines of prior the
Slide 14: FELIX: remission rate and MRD by status at lymphodepletion
FELIX: remission rate and MRD by status at lymphodepletion High MRD-negative remission rates were observed after obe-cel 14 Morphologic disease* (n = 98) • 74% of patients had CR/CRi (n = 73) • 95% of evaluated responders were MRD-negative‡ No morphologic disease (n = 29) • 100% of evaluable patient
Slide 15: FELIX: CR/CRi subgroup analysis per IRRC
FELIX: CR/CRi subgroup analysis per IRRC Obe-cel demonstrated high CR/CRi rates across all subgroups 15 Subgroup Total, n (%) ORR, % (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, 8
Slide 16: FELIX: EFS in all treated patients
FELIX: EFS in all treated patients* The event-free survival estimate at 12 months was 50% 16 • The median follow-up time was 16.6 months (range: 3.7−36.6 months) • 17/99 (17%) responders proceeded to SCT while in remission • A pooled analysis from the ALLCAR19 and FELIX Phase Ib studies will be pres
Slide 17: FELIX: obe-cel persistence in responders
FELIX: obe-cel persistence in responders Obe-cel has high expansion and long-term persistence 17 • CAR-T persistence was detected in 72% of ongoing responders at the latest follow-up AUC, area under the curve; CAR-T, chimeric antigen receptor T-cell; Cmax, maximum concentration; CV, coefficient of v
Slide 18: FELIX: leukemic burden in all treated patients
FELIX: leukemic burden in all treated patients Leukemic burden at screening is not predictive of leukemic burden prior to lymphodepletion 18 *Bridging therapy per physician’s choice, including inotuzumab ozogamicin BM, bone marrow 16% 28% 53% 40% 31% 31% BM blasts % at screening BM blasts % prior to
Slide 19: FELIX: EFS by leukemic burden prior to lymphodepletion
FELIX: EFS by leukemic burden prior to lymphodepletion* Lower leukemic burden is associated with better outcomes 19 BM blasts % prior to lymphodepletion <5% (n = 36) ≥5−≤75% (n = 51) >75% (n = 40) Median EFS (95% CI), months NE 15.0 (6.6, NE) 4.5 (1.5, 9.0) 6-month EFS (95% CI), % 83 (65, 92) 72 (57
Slide 20: FELIX: CRS and ICANS
FELIX: CRS and ICANS Low rates of Grade ≥3 CRS and/or ICANS were observed BM blasts % at lymphodepletion 2% 7% 20 0 40 60 80 100 In ci de nc e, % CRS ICANS 0% 4% 3% 20 0 40 60 80 100 In ci de nc e, % <5% ≥5−≤75% >75% 0% 6% 15% 20 0 40 60 80 100 In ci de nc e, % <5% ≥5−≤75% >75% CRS and ICANS in all
Slide 21: FELIX: Phase Ib/II conclusions
FELIX: Phase Ib/II conclusions 21 • 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 22: FELIX: TEAEs
FELIX: TEAEs Favorable safety profile CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; TEAE, treatment emergent adverse event TEAEs that occurred in ≥20% of patients regardless of causality All treated patients (N = 127) Any grade, % Grade ≥3, % Patients
Slide 23: Acknowledgments
Acknowledgments 23 • 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
Slide 24: Longer-term follow up in B-ALL
Longer-term follow up in B-ALL ASH 2023 Pooled analysis from ALLCAR 19 Phase 1b and FELIX Phase 1b trials in B-ALL Dr. Christian Itin, CEO, Autolus
Slide 25: ALLCAR19 and FELIX are investigating obe-cel in adults with B-cell malignancies
ALLCAR19 and FELIX are investigating obe-cel in adults with B-cell malignancies Developing Next Generation Programmed T Cell Therapies 25 *Data cut-off: November 01, 2023; †Data cut-off: September 13, 2023. B-ALL, B-cell acute lymphoblastic leukemia; B-CLL, B-cell chronic lymphocytic leukemia; B-NHL
Slide 26: Long-term follow up in R/R B-ALL demonstrates favorable EFS and OS
Long-term follow up in R/R B-ALL demonstrates favorable EFS and OS Developing Next Generation Programmed T Cell Therapies 26 Median follow up 36.5 months; pooled analysis of Ph. 1b ALLCAR19 and Ph. 1b FELIX study in r/r B-ALL *Censored for allo-HSCT and other anti-cancer treatment. Investigator-asse
Slide 27: Durable remissions in patients with R/R B-ALL and no new safety signals
Durable remissions in patients with R/R B-ALL and no new safety signals Developing Next Generation Programmed T Cell Therapies 27 All patients in ongoing remission were MRD negative at the last assessment Investigator-assessed disease evaluations were performed locally by CT and BM biopsy for B-ALL.
Slide 28: Prolonged persistence seen in most long-term R/R B-ALL responders
Prolonged persistence seen in most long-term R/R B-ALL responders Developing Next Generation Programmed T Cell Therapies 28 Obe-cel persistence since infusion Ongoing CAR T persistence 12 months: 60.6% (95% CI: 38.9–76.8) 24 months: 55.1% (95% CI: 33.1–72.6) Loss of CAR T persistency was defined as
Slide 29: Obe-cel Next Steps
Obe-cel Next Steps Commercial Launch Readiness in r/r aALL Starting Phase 1 SLE study Dr. Christian Itin, CEO, Autolus
Slide 30: Obe-cel steps to commercialization in r/r adult ALL
Obe-cel steps to commercialization in r/r adult ALL 30 Roadmap to a 2024 commercial launch H2 2023 H1 2024 BLA submitted to FDA Filing of Biologics License Application (BLA) to U.S. Food and Drug Administration (FDA) Regulatory Manufacturing Commercialization EU authorization application Filings of
Slide 31: Potential best-in-class risk/benefit profile in pivotal FELIX trial in adult ALL
31 Potential best-in-class risk/benefit profile in pivotal FELIX trial in adult ALL Low rates of high-grade CRS and ICANS across all patients Obe-cel’s potential advantages Deep cut into the CD19+ B and plasma cell compartment to remove all autoreactive clones High treatment effect enables small
Slide 32: Expanding the obe-cel opportunity
Expanding the obe-cel opportunity Deep value program with potentially broad applicability
Slide 33: The obe-cel product family and franchise opportunity
The obe-cel product family and franchise opportunity • Optimal CD19 CAR design • Potential best-in-class efficacy and safety profile • Supported by state-of-the-art manufacturing • Supported by mature FELIX clinical/CMC package B-ALL and B-NHL B-cell mediated autoimmune disease Developing Next Gener
Slide 34: Obe-cel in B-NHL/B-CLL: High response rates with durable remissions
Obe-cel in B-NHL/B-CLL: High response rates with durable remissions Data from ALLCAR19 extension: Long term persistence driving durable outcomes • No ≥ grade 3 CRS and ICANS reported 34Developing Next Generation Programmed T Cell Therapies Median follow-up 20.9 months (range 0.9 – 36.2) B-NHL/CLL A
Slide 35: AUTO8: combining a sensitive BCMA CAR with the CD19 CAR from obe-cel
AUTO8: combining a sensitive BCMA CAR with the CD19 CAR from obe-cel Designed to induce deep and durable responses Co nf id en tia l BCMA CAR Novel format CAR designed to be highly sensitive to low BCMA density found on malignant plasma cells CD19 CAR Coupled to obe-cel to drive persistence and lon
Slide 36: Initial data from MCARTY Phase 1 showed clinical responses in all patients
Initial data from MCARTY Phase 1 showed clinical responses in all patients Developing Next Generation Programmed T Cell Therapies 36 Both D8 BCMA CAR and AUTO8 associated with high response rate AUTO8, D8 BCMA + obe-cel CARs; Median follow up 6 months (range 1–15); Lee et al., ASH 2023, Publication
Slide 37: Initial safety data MCARTY Phase 1 study
Initial safety data Phase 1 MCARTY study Developing Next Generation Programmed T Cell Therapies 37 D8 BCMA CAR and AUTO8 did not result in severe ICANS/CRS and were well tolerated with no DLTs • CRS in 10 patients (91%) and all low grade; no patients reported ICANS • Tocilizumab given to 7 patients
Slide 38: Upcoming news flow
Upcoming news flow
Slide 39: Autolus planned news flow
Autolus planned news flow 39Developing Next Generation Programmed T Cell Therapies Anticipated Milestone or Data Catalysts Timing Obe-cel Biologics License Application (BLA) to FDA Complete Obe-cel FELIX data update at ASH Complete AUTO8 update (MCARTY) at ASH Complete AUTO6NG Phase 1 study start (M
Slide 40: Summary
Summary
Slide 41: Building a leading CAR T company developing transformational therapies for cancer and autoimmune diseases
Building a leading CAR T company developing transformational therapies for cancer and autoimmune diseases 41 • FELIX pivotal trial showed high ORR, encouraging EFS and favourable tolerability with low levels of high-grade CRS and ICANS • BLA submitted to FDA • EMA submission planned for 1H 2024 • Es
Slide 42: Thank you
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