Autolus Therapeutics Plc · NASDAQ:AUTL
Autolus Therapeutics — ASH 2020 (American Society of Hematology Annual Meeting)
53 slides from Autolus Therapeutics's conference presentation, Dec 7, 2020
Slide 1: AUTO1 and AUTO3 Data Update - ASH 2020
Nasdaq: AUTL AUTO1 and AUTO3 Data Update - ASH 2020 December 2020 December 2019 Nasdaq: AUTL Exhibit 99.3
Slide 2: Disclaimer
Disclaimer These slides and the accompanying oral presentation contain forward-looking statements within the meaning of the “safe harbor” provisions of The Private Securities Litigation Reform Act of 1995, including statements about the safety, therapeutic potential and commercial opportunity of AUT
Slide 3: Agenda
Agenda Welcome and Introduction: Dr. Christian Itin, Chairman and CEO AUTO3 Data Review: Dr. Robert Chen, Executive Director, AUTO3 Program Lead Commercial Opportunity in DLBCL : Brent Rice, Vice President, Chief Commercial Officer AUTO1 Data Review: Dr. Nushmia Khokhar, Head of Clinical Development
Slide 4: Welcome and introduction
Welcome and introduction Dr. Christian Itin Chairman and CEO
Slide 5: Broad expertise in CAR T therapy development and market access
Broad expertise in CAR T therapy development and market access Dr. Nushmia Khokhar SVP, Head of Clinical Development Board certified oncologist, lead several successful registration trials within industry including global daratumumab program at Janssen Oncology Dr. Robert Chen Executive Director, Cl
Slide 6: AUTO3 safety and efficacy highlights
Safety data supports feasibility of outpatient administration AUTO3 was observed to be well tolerated, with low rates of cytokine release syndrome (CRS) and neurotoxicity (NT) reported No prophylactic measures of any kind have been used to manage patients in this study Manageability in the outpatien
Slide 7: AUTO1 sustained CRs without subsequent stem cell transplant
High level of sustained CRs, achieved without subsequent stem cell transplant Durability of remissions highly encouraging Across all treated patients, event free survival (EFS) at six and 12 months is 69% and 52%, respectively AUTO1 remains well tolerated, despite patients having high disease burden
Slide 8: AUTO3 Data Review
* American Society of Hematology – December 2020 Data Review Dr. Robert Chen Executive Director, AUTO3 Program Lead Phase 1/2 study of AUTO3, the first bicistronic chimeric antigen receptor (CAR) targeting CD19 and CD22, followed by an anti-PD1 in patients with relapsed/refractory (r/r) Diffuse Larg
Slide 9: CD19 CARs are active in r/r DLBCL; unmet need remains
CD19 CARs are active in r/r DLBCL However unmet need remains with CD19 CAR T cell therapy 29-37% durable CRR in DLBCL1,2 The potential causes for relapse include: PD-L1 upregulation3 which contributes to CAR T exhaustion CD19 antigen loss4 Rate of severe (grade ≥3) cytokine release syndrome (CRS 13-
Slide 10: AUTO3: First CD19 and CD22 Targeting Bicistronic CAR
Dual antigen targeting Two independent CARs delivered in single retroviral vector Humanized binders CD22 CAR with novel pentameric spacer OX40/41BB costimulatory domains designed to improve persistence Independently target CD19 and CD22 AUTO3: First CD19 and CD22 Targeting Bicistronic CAR Gamma Retr
Slide 11: Alexander Study Design
Alexander Study Design AUTO3-DB1, single-arm, open-label, multi-center, Phase 1/2 study Cohort 1 Cohort 2 Phase II Phase I Dose in x106 CD19/CD22 CAR T Cells 50 50 150 450 900 450 900 Dose Escalation Cohort Outpatient Cohort 150-450 RP2D @RP2D (Efficacy Cohort) DLBCL NOS, high grade B cell lymphoma,
Slide 12: Outpatient Expansion Cohort
Phase 1 Outpatient Expansion Cohort Subjects who do not have caregiver support (in line with institutional outpatient transplant guidelines) for outpatient/ambulatory care setting Subjects who are staying greater than 60 minutes (or whatever is permissible per institutional outpatient transplant gui
Slide 13: Baseline Patient Characteristics: All Patients
Baseline Patient Characteristics: All Patients Baseline Patient Characteristics N=49 Age, median (min-max) 59 (27-83) Gender, n Male, Female 29, 20 Current Histology, n DLBCL NOS tDLBCL High Grade B Cell Lymphoma Primary Mediastinal Large B Cell Lymphoma 34 (69%) 11 (22%) 3 (6%) 1 (2%) Molecular Ris
Slide 14: Treatment Emergent Adverse Events
Treatment Emergent Adverse Events ≥ 25% and SAE ≥ 5% Majority of ≥ Grade 3 AEs are haematological Two patients had death possibly related to AUTO3. One in the setting of disease progression and multiorgan failure and other due to infection in a patient with secondary HLH AEs (Total N = 49) All Grade
Slide 15: Safety by Cohort
Safety by Cohort 50 x106 AUTO3 no pem (N=4) 50 x106 AUTO3 D14 pem (N=3) 150-450 x106 AUTO3 D14 pem (N=8) 150-450 x106 AUTO3 D-1 pem Inpt (N=17) 150-450 x106 AUTO3 D-1 pem Outpt (N=17) Total (N=49) Safety CRS All Grades 1 0 4 5 7 17 (35%) CRS ≥ Grade 3 0 0* 0 0 1 1 (2%) NTX All Grades 1 0 0 1 1 3 (6%
Slide 16: Cytokine Release Syndrome (CRS)
Cytokine Release Syndrome (CRS) No prophylactic measures of any kind Median time to CRS 2 days (1-36), Median duration 3 days (1-19) Eight patients received tocilizumab (16%) No patients received steroids CRS grading as ASCT/ASBMT (Lee et al 2019) Data Cut-off Date: 30-Oct-2020 Low rates of CRS Tota
Slide 17: Neurotoxicity (NT/ICANS)
Neurotoxicity (NT/ICANS) No prophylactic measures of any kind No NT of any grade in patients that achieved CR All NT atypical in context of tumor progression with zero to minimal CAR T expansion in peripheral blood 1st case of NT (G3): Day 53. Duration 5 days (G2). The same symptoms of facial/muscle
Slide 18: Efficacy Data by Cohort
Efficacy Data by Cohort 50 x106 AUTO3 no pem (N=4) 50 x106 AUTO3 D14 pem (N=3) 150-450 x106 AUTO3 D14 pem (N=8) 150-450 x106 AUTO3 D-1 pem Inpt (N=17) 150-450 x106 AUTO3 D-1 pem Outpt (N=17) Total (N=49) N Evaluable* 4 2 8 15 14 43 ORR (CR+PR) 2 (50%) 2 (100%) 5 (63%) 10 (67%) 9 (64%) 28 (65%) CR 1
Slide 19: Efficacy Data - Best Overall Responses
Efficacy Data - Best Overall Responses Across all doses CRR of 51% (n=43) Doses ≥ 300 x 106, CRR of 62% (n=26) Doses ≥ 450 x 106, CRR of 73% (n=15) *Evaluable = PET positive disease prior to start of pre-conditioning and infused at least 28 days prior to data Cut-off date Data Cut-off Date: 30-Oct-2
Slide 20: Disease Assessment of CR Patients
Disease Assessment of CR Patients Data Cut-off Date: 30-Oct-2020 16/22 (73%) without progression, median follow up of 4 months Time from AUTO3 infusion (months) 50-450 x106 D14, D35, D56 Pembro 3x Doses Pembro 150-450x106 D-1 Pembro 1x Dose Pembro 50 x106 No Pembro AUTO3 Dose, x106 450 150 300 450 3
Slide 21: Cellular Kinetics by Best Overall Response
Cellular Kinetics by Best Overall Response Evaluable = PET positive disease prior to start of pre-conditioning, infused at least 28 days prior to data Cut-off date and with at least one sample providing evaluable cellular kinetic data Data Cut-off Date: 30-Oct-2020 CR/PR are associated with higher e
Slide 22: AUTO3 Healthcare Utilizations in Outpatient Cohort
AUTO3 Healthcare Utilizations in Outpatient Cohort 5 patients received AUTO3 outpatient but admitted (due to FN and CRS) Median duration of hospitalisation was 5 days (range 1-9 days) Data Cut-off Date: 30-Oct-2020 Outpatient infusion of AUTO3 is feasible 150-450 x106 AUTO3 D-1 pem Outpt (N=17) AUTO
Slide 23: Conclusions
Conclusions AUTO3 has a tolerable and best-in-class safety profile: 35% CRS (2% ≥ Grade 3 CRS) with primary infusion 6% NT/ICANs* (4% ≥ Grade 3 NT/ICANs) Patients that achieved CRs, where robust expansion was observed, no severe NT of any grade was seen All three cases of NT in setting of disease pr
Slide 24: Commercial Opportunity – DLBCL
Commercial Opportunity – DLBCL Brent Rice Vice President, Chief Commercial Officer, US
Slide 25: Outpatient Cohort reinforces AUTO3 feasibility in Outpatient Setting
Outpatient Cohort reinforces AUTO3 feasibility in Outpatient Setting AUTO3 has the potential to be a true outpatient therapy Source: US Retrospective Claims Analysis by Site of Distribution *Autolus approximate estimates Patients receive approved products as inpatients in CoEs because of the high ra
Slide 26: DLBCL: approved CAR T's are unable to penetrate outpatient setting
DLBCL: approved CAR T’s are unable to penetrate outpatient setting Creates significant opportunity for AUTO3 with potential to go where patients reside 97% of patients receive approved CAR Ts as inpatients in CoEs because of the high rate and severity of toxicities and the need for intensive patient
Slide 27: AUTO3 continues to deliver on promise for patients in outpatient setting
AUTO3 continues to deliver on promise for patients in outpatient setting Across all lines of DLBCL the vast majority of patients are treated outside of COEs Going where patients are treated could eliminate the challenges involved in establishing referral networks Clinical profile and potential for f
Slide 28: AUTO1 Data Review: ALLCAR19 Updated Data
* American Society of Hematology – December 2020 Data Review Dr. Nushmia Khokhar Head of Clinical Development ALLCAR19: Updated Data Using AUTO1, a Novel Fast-Off Rate CD19 CAR in Adult Relapsed/Refractory B-Acute Lymphoblastic Leukaemia*
Slide 29: Adult B-Acute Lymphoblastic Leukemia
Adult B-Acute Lymphoblastic Leukemia: Adult B-ALL prognosis is poor; long-term remission rates limited to 30-40% 50% of all adult patients will relapse, with 5-year OS 7% (Fielding et al., 2007) Currently the only curative option for r/r ALL is allo-SCT in CR2, but <50% achieve CR2 Blinatumomab and
Slide 30: ALLCAR19 Study Design
ALLCAR19 Study Design B-ALL arm ALLCAR19 (NCT02935257) Cy 60 mg/kg Registration Leucapheresis/Enrolment Pre-Conditioning AUTO1 Infusion 1st Disease Assessment Day-6 Day 0 * Day 28 Flu 30mg/m2 Day 9 ** Bridging Therapy as Necessary AUTO1 Manufacturing Safety & Efficacy Follow Up M24 EoS No G3-5 CRS/I
Slide 31: ALLCAR19 Study: Endpoints and eligibility
Grade 3-5 toxicity causally related to the ATIMP Feasibility of adequate leucapheresis & generation of AUTO1 CAR T-cells Age 16 to 65 years High risk or relapsed histologically confirmed CD19+ B-ALL following standard therapy requiring salvage in whom alternative therapies are deemed inappropriate b
Slide 32: ALLCAR19 Manufacturing: Product characteristics & feasibility
100% of successful harvests result in a QP released product Semi-automated closed manufacturing process was used in 18/24 products Advantages of closed process includes: rapid, standardised manufacture trend towards lower exhaustion markers enrichment for Tcm and Tnaive CAR+ cells (47%) Mean transdu
Slide 33: Patient Characteristics: Treated (n=20)
20 patients have been infused (data cut off 12-Nov-2020) Patient Characteristics: Treated (n=20) Baseline Characteristics N=20 (%) Median age, years (range) 43 (18-62) Gender 13M/7F Chromosomal/Molecular status Ph+ (bcr-abl) MLL Other Normal Failed 6 (30%) 1 (5%) 8 (40%) 4 (20%) 1 (5%) Prior lines o
Slide 34: AUTO1 Pharmacokinetics: Expansion and persistence by qPCR
* Mueller, KT et. al. Blood 130(21) 2017 AUTO1 Pharmacokinetics: Expansion and persistence by qPCR M12 ALLCAR19 qPCR PK all patients (n = 19) *Mueller 2017 (responders) AUC DO-28 (Geometric Mean) (Copies/ꙡg x days) 750 320 342 732 Half life (Median Days) 17 (Range 11-29) 14.2 Max CART T Level (Geome
Slide 35: Safety Profile
CRS All patients who developed Grade 2 CRS had high burden B-ALL Tocilizumab was used in 7/20 patients (35%) Neurotoxicity (ICANS) ≥ Grade 2 ICANS was reported in 4/20 patients: all had ≥ 50% blasts; all cases were preceded by CRS 3/4 cases resolved to G1 in <24h with steroids, 1/4 cases resolved to
Slide 36: Efficacy & Duration
Efficacy & Duration MRD < 10-4 by PCR or < 5 x 10-4 based on limits of detection of assay Data Cut-off 12-Nov-2020, Evaluable = All patients with at least M1 follow-up or death prior to Month 1 21 Closed Process Open Process CD19 -ve Relapse Not Evaluable Allogenic BMT Death Complete Remission MRD n
Slide 37: AUTO1: Efficacy Overview
AUTO1: Efficacy Overview N = All patients with at least M1 follow-up or RIP prior to Month 1. Event = death or morphological relapse. DOR, EFS and OS data are preliminary considering the small n All patients Est [95% CI] Closed process Est [95% CI] N * 19 13 ORR 84% 92% MRD Neg CR 84% 92% DOR Median
Slide 38: ALLCAR19 Study: Extending eligibility to Indolent NHL, HG-NHL and CLL
ALLCAR19 Study: Extending eligibility to Indolent NHL, HG-NHL and CLL relapsed/refractory (r/r) Follicular Lymphoma r/r Mantle Cell Lymphoma r/r Marginal Zone Lymphoma ≥2 prior lines of therapy including Rituximab and anthracycline Cohort 1: Indolent B-NHL (Dose = 200 million CD19 CAR T-cells) r/r D
Slide 39: ALLCAR19 Study: Cohort 1 Indolent NHL products and demographics
ALLCAR19 Study: N=6 products QP released Semi-automated, closed manufacturing Tcm/Tnaive CAR+ (36%) Transduction efficiency (mean 76%) Cohort 1:Indolent NHL- products and demographics Baseline Characteristics N=8 (%) Median age, years (range) 57 (39 - 68) Gender 6M/2F Histological diagnoses MCL FL 2
Slide 40: ALLCAR19 Study: Cohort 1 toxicity, responses, engraftment
ALLCAR19 Study: Cohort 1:Indolent NHL- toxicity, responses, engraftment Engraftment Toxicity Responses based on Lugano Criteria and IHC (CD20) N = 4 CRS Any grade ≥ Grade 2 3/4 0/4 Neurotoxicity (ICANS) Any grade 0/4 ≥ Grade 3 Neutropenia Day -6 Day 28 0/4 0/4 MONTH 1 PRE-LD N = 4 CMR 4/4 PR 0/4 SD
Slide 41: AUTO1: Conclusions
Tolerable Safety Profile was observed: Despite high disease burden and despite heavily pre-treated patient population on study No Grade 3 CRS was observed Only 3/20 patients developed Grade 3 ICANS (rapid resolution with steroids) Robust expansion and prolonged CAR persistence was observed Efficacy
Slide 42: Commercial Opportunity – Adult ALL
Commercial Opportunity – Adult ALL Brent Rice Vice President, Chief Commercial Officer, US
Slide 43: No approved CAR T therapy for adult ALL patients
No approved CAR T therapy for adult ALL patients Transformative therapy needed to address high unmet need despite current SOC *SEER and EUCAN estimates (respectively) for US and EU epi Combination chemotherapy enables 90% of adult ALL patients to experience CR, but only 30% to 40% will achieve long-
Slide 44: Key Features of a Successful Therapy for Adult ALL
Key Features of a Successful Therapy for Adult ALL Adult ALL Challenge Product Property CAR T Feature Fast proliferating disease Very high level of anti-leukemic activity Rapid CAR T mediated kill and high level of CAR T expansion Almost stem cell like nature of leukemic cells Sustain long term pres
Slide 45: AUTO1 vs Standard of Care cross study comparison
1AUTO1 Standard of Care All patients 2Blinatumumab 3Inotuzumab Patient Numbers 19 271 218 CR Rate 84% 44% 80.7% EFS 6m (EFS 12m) 69% (52%) 31% mPFS 5m CRS ≥ Grade 3† 0% 3% 0% Neurotox ≥ Grade 3† 15%* 13% 0% Other notable toxicities 14% Hepatic VoD * Observed in patients with > 50% tumor burden 1. Ro
Slide 46: Adult ALL is a promising commercial opportunity with limited competition
Adult ALL is a promising commercial opportunity with limited competition R/R adult ALL is three times the size of r/r pediatric ALL Source: DRG AUTO 1 r/r Adult ALL r/r Pediatric ALL Projected R/R patients in US & EU ~3,000 addressable patient population in last line setting Projected R/R patients i
Slide 47: Capitalizing on the unique profile of AUTO1 in Adult ALL
Capitalizing on the unique profile of AUTO1 in Adult ALL Exploration of AUTO1 activity in additional B-Cell malignancies PRODUCT INDICATION TARGET Phase 1 Pivotal AUTO1 AUTO1 AUTO1 AUTO1/22 Adult ALL iNHL & CLL Primary CNS Lymphoma* Pediatric ALL CD19 CD19 CD19 CD19 & CD22 CAROUSEL CARPALL ext. ALLC
Slide 48: AUTO1 is designed for potential Best-In-Class Efficacy and Safety
AUTO1 is designed for potential Best-In-Class Efficacy and Safety Novel CD19 CAR designed for use as a stand-alone curative therapy Potential transformative clinical profile with high rates of durable complete responses Highly differentiated clinical profile with potential for hospital outpatient tr
Slide 49: Summary and Next Steps
Summary and Next Steps Dr. Christian Itin Chairman and CEO
Slide 50: Summary of AUTO1 and AUTO3 Clinical Programs
Summary of AUTO1 and AUTO3 Clinical Programs AUTO1 High level of sustained CRs, durability of remissions highly encouraging Well tolerated, despite high disease burden and heavy pre-treatment of the patients in this study Currently enrolling Autolus’ first Ph1b / 2 pivotal program with data planned
Slide 51: Multiple clinical milestones planned through Q4 2020 / 2021
Multiple clinical milestones planned through Q4 2020 / 2021 PRODUCT INDICATION TARGET EVENT B Cell Malignancies T Cell Lymphoma Solid Tumors AUTO1 AUTO1/22 Adult ALL Pediatric ALL CD19 CD19 & CD22 Allogeneic Approach Multiple Myeloma Ph1 long-term follow up, AL-1 data in 2022 Started Ph1 Q4 2020 AUT
Slide 52: Q&A
Q&A Dr. Christian Itin (Chairman and CEO) Dr. Martin Pule (Founder and CSO) Andrew Oakley (CFO) Dr. Nushmia Khokhar (SVP, Head of Clinical Development) Dr. Robert Chen (Executive Director, AUTO3 Program) Brent Rice (VP, Chief Commercial Officer, US)
Slide 53: Thank you
~ Thank you
Autolus Therapeutics — ASH 2020 (American Society of Hematology Annual Meeting) on 6ix