Autolus Therapeutics plc · NASDAQ:AUTL
Autolus Therapeutics — Investor Presentation (January 2021)
42 slides from Autolus Therapeutics's investor presentation, January 2021
Slide 1: Developing Next Generation Programmed T Cell Therapies
Nasdaq: AUTL Developing Next Generation Programmed T Celltitle Click to edit Master Therapies style January 2021
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: Lead Clinical Programs
Lead Clinical Programs Striving for best-in-class therapies 3
Slide 4: Driving value with potential best-in-class adult ALL program
Driving value with potential best-in-class adult ALL program o Plan to partner AUTO3 ahead of Full data for AUTO1 progressing into next phase of Focusing on delivering – AL-1 study in development AUTO1, a potentially adult expected in o Additional value steps in T cell transformational 2022 lymphoma
Slide 5: Broad pipeline of clinical programs
Broad pipeline of clinical programs Designed to address limitations of current T cell therapies PRODUCT INDICATION TARGET PHASE 1/2 PIVOTAL* AUTO1 Adult ALL CD19 ALLCAR19 AUTO1-AL1 AUTO1 NHL † CD19 ALLCAR19 AUTO1 PCNSL † † CD19 CAROUSEL AUTO1/22 Pediatric ALL CD19 & CD22 CARPALL AUTO3 DLBCL CD19 & C
Slide 6: Adult Acute Lymphoblastic Leukemia
Adult Acute Lymphoblastic Leukemia AUTO1— Potential as a standalone therapy 6
Slide 7: No approved CAR T therapy for adult ALL patients
No approved CAR T therapy for adult ALL patients Successful therapy requires high level of activity and sustained persistence paired with good tolerability HIGH UNMET MEDICAL NEED ALL is a o Combination chemotherapy enables 90% of adult ALL patients to experience CR, but only 30% to 40% will achieve
Slide 8: AUTO1 is designed for durable responses and low incidences of severe CRS
AUTO1 is designed for durable responses and low incidences of severe CRS Key features differ to conventional CARs inc CONVENTIONAL CD19 CARS AUTO1 o Approved and late clinical stage CD19 CAR Ts o AUTO1 has an optimized CD19 CAR with a use identical high affinity CD19 binder lower (40x) affinity for
Slide 9: AUTO1 has potential for transformational outcomes in adult ALL
AUTO1 has potential for transformational outcomes in adult ALL Data presented at ASH 2020, with a data cut-off date November 12, 2020 o High level of sustained CRs, achieved without subsequent stem cell transplant o Durability of remissions highly encouraging – Across all treated patients, event fre
Slide 10: AUTO1 is well tolerated, even in patients with high disease burden
AUTO1 is well tolerated, even in patients with high disease burden CRS (Lee Criteria) Neurotoxicity (ICANS*) ≥ Grade 3 Neutropenia o CRS (any) in 10/20 o ICANS (any) in 4/20 o 7/20 preceded o Grade 2 in 7/20 o Grade 2 in 1/20 treatment o ≥ Grade 3 CRS in o Grade 3 in 3/20 o 8/17 at D28, most 0/20 re
Slide 11: Responses are durable without need for transplant
Responses are durable without need for transplant MRD negative CRs ongoing past 24 months observed ALL-29 ALL-24 MEDIAN FOLLOW-UP 16.9 PATIENT ID ALL-22 MONTHS (RANGE 0.6 – 30.5 ALL-20 M) Complete Remission CLOSED PROCESS ALL-19 Not Evaluable ALL-18 MRD negative CR ALL-17 (PCR/Flow) ALL-16 Ongoing D
Slide 12: Event-free survival supports AUTO1's unique profile
Proportion alive and progres Event-free survival of 52% at 12 months supports AUTO1’s unique profile All patients Closed processɫ Est [95% CI] Est [95% CI] N* 19 13 ORR 84% 92% 1.00 MRD Neg CR 84% 92% DOR 0.75 Median Not reached Not reached AUTO1: Efficacy Overview 6 months 81% [52%, 94%] 83% [48%,
Slide 13: AUTO1 has potential as a standalone therapy
AUTO1 has potential as a standalone therapy A cross study comparison of AUTO1 vs current standard of care AUTO11 Standard of Care All patients * Observed in Blinatumomab2 Inotuzumab3 patients with Patient Numbers 19 > 50% tumor 271 218 burden CR Rate 84% 1. Roddie et al., 44% 80.7% ASH 2020 EFS 6m 6
Slide 14: 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 estimated* to be three times the size of r/r pediatric ALL AUTO1 r/r Adult ALL r/r Pediatric ALL Estimated R/R patients Estimated R/R patients ~3,000 ~1,000 addressable patient addressable patient population po
Slide 15: Blincyto and Besponsa sales suggestive of a meaningful opportunity
Blincyto and Besponsa sales suggestive of a meaningful opportunity in adult ALL 356 + 21% o Blincyto sales price estimated to be $175k (based on 295 1.7 cycles) resulting in approx. 1,400 -1,800 commercial patients (includes pediatric patients) o Opportunity to address entire relapse / refractory ad
Slide 16: Preliminary Ph1 data supports development as a standalone therapy
Preliminary Ph1 data supports development as a standalone therapy AUTO1 is the first Autolus program to move into a pivotal program o Ph1b run-in component, prior to Pivotal program, CTA approved single arm Ph2 pivotal study AUTO1-AL1, in by the MHRA o 100 relapsed/refractory adult in January 2020 a
Slide 17: 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 Adult ALL CD19 ALLCAR19 AUTO1-AL1 AUTO1 iNHL & CLL CD19 ALLCAR19 ext. Primary CNS AUTO1 CD19 CAROUSE Lymphoma* L AUTO1/22 Pediatric
Slide 18: Initial data suggest encouraging signals in other B cell malignancies
Initial data suggest encouraging signals in other B cell malignancies Flow cytometric CAR %CD3 (PB) (log-scale) ALLCAR19 Study extension Cohort 1: Extending to Indolent NHL TOXICITY RESPONSES BASED ON LUGANO CRITERIA AND IHC (CD20) N=4 N=4 PRE-LD MONT H1 CRS Any grade 3/4 CMR 4/4 ≥ Grade 2 0/4 PR 0/
Slide 19: Diffuse Large B Cell Lymphoma
Diffuse Large B Cell Lymphoma AUTO3 — tailored for DLBCL 19
Slide 20: AUTO3: First CD19 and CD22 targeting bicistronic CAR
AUTO3: First CD19 and CD22 targeting bicistronic CAR Gamma Retroviral-Based Vector with RD114 Pseudotype aCD19 aCD22 oAUTO3 is designed to achieve a high level of scFV scFV clinical activity, favourable safety profile and low rate of relapses due to CD19 antigen loss -S-S- oDesign features: CD8aSTK
Slide 21: DLBCL: approved CAR Ts are unable to penetrate outpatient setting
DLBCL: approved CAR Ts are unable to penetrate outpatient setting Creates significant opportunity for AUTO3 with potential to go where patients are treated PERCENTAGE OF PATIENTS WHO o 97% of patients receive approved CAR Ts as inpatients in CURRENTLY RECEIVE A CAR T IN CoEs * because of OUTPATIENT
Slide 22: Low rates of CRS and low rates of NT observed across all dose levels
Low rates of CRS and low rates of NT observed across all dose levels Cytokine Release Syndrome and Neurotoxicity — by cohort 50 x106 50 x106 150-450 x106 150-450 x106 150-450 x106 Total AUTO3 no pem AUTO3 D14 pem AUTO3 D14 pem AUTO3 D-1 pem AUTO3 D-1 pem (N=49) (N=4) (N=3) (N=8) Inpt (N=17) Outpt (N
Slide 23: Efficacy seen across all dose ranges
Efficacy seen across all dose ranges Response data by cohort 50 x106 50 x106 150-450 x106 150-450 x106 150-450 x106 Total AUTO3 no pem AUTO3 D14 pem AUTO3 D14 pem AUTO3 D-1 pem AUTO3 D-1 pem (N=49) (N=4) (N=3) (N=8) Inpt (N=17) Outpt (N=17) N Evaluable* 4 2 8 15 14 43 ORR (CR+PR) 2 (50%) 2 (100%) 5
Slide 24: Outpatient infusion of AUTO3 appears feasible
Outpatient infusion of AUTO3 appears feasible Healthcare utilization in outpatient cohort 150-450 x106 AUTO3 D-1 pem Outpt (N=17) AUTO3 infusion 4 o5 patients received AUTO3 outpatient but inpatient admitted (due to FN* and CRS) 13 AUTO3 infusion oMedian duration of hospitalisation was 5 days outpat
Slide 25: AUTO3 continues to show differentiated product profile
AUTO3 continues to show differentiated product profile Data presented at ASH 2020, with data cut-off date October 30, 2020 o Key Ph1 observations: oPath forward for development of AUTO3 • High level of complete remissions (CR) of 51% • Ph2 designs under evaluation: overall 3L r/r DLBCL setting • A
Slide 26: T Cell Lymphoma
T Cell Lymphoma AUTO4 and AUTO 5 — tailored for T Cell Lymphoma 26
Slide 27: T Cell Lymphoma
T Cell Lymphoma No standard of care after first relapse and no T cell therapy approved AUTOLUS USES THREE KEY ELEMENTS o T cell lymphoma is an aggressive TO disease with a very poor ADDRESS T CELL LYMPHOMA’S—AUTO4, prognosis AUTO5 AND A COMPANION DIAGNOSTIC for patients TEST > ~40% of T cell lymphom
Slide 28: Unique targeting of TRBC1 & TRBC2 opens new therapeutic approach
Unique targeting of TRBC1 & TRBC2 opens new therapeutic approach AUTO4/5 in Peripheral T Cell Lymphoma DIFFERENCES BETWEEN TRBC1 AND TRBC2 ARE SMALL T CELL RECEPTOR TRBC1 ANTIBODY ANTIBODY BINDING DATA 1.5 1.5 Jovi-1 mutants Jovi-1 mutants o AUTO4 clinical study, LibrA T1, in progress 450nm (OD 1.0
Slide 29: Encouraging signal from AUTO4 treated patient
Encouraging signal from AUTO4 treated patient Clinical outcome of patient 1 o57 yr old with Angioimmunoblastic T cell BASELINE PET/CT SCAN MONTH 1 PET/CT SCAN PRE-AUTO4 TREATMENT lymphoma oPast treatments include CHOP (CR) & IVE (refractory) oAUTO4 Treatment Treated with 25x106 anti-TRBC1 CAR T cell
Slide 30: Pipeline
Pipeline A broad portfolio of next generation modular T cell therapies 30
Slide 31: A broad toolkit which is core to our strategy of modular innovation
A broad toolkit which is core to our strategy of modular innovation Advanced T cell programming Activity Allogeneic Pharmacologi Enhancement Programming Advanced Targeting cal Viral Vector Modules Modules Viral Vector Modules Control CAR CAR CTRL Modules ENH AUTO Fast off Rate CARs Safety dSHP2 GvHD
Slide 32: Broad pipeline of next generation programs
Broad pipeline of next generation programs Designed to address limitations of current T cell therapies PRODUCT INDICATION TARGET PRECLINICAL PHASE 1 AUTO1/22 Pediatric ALL CD19 & CD22 Started Q4 2020 AUTO5 TRBC2+ Peripheral TCL TRBC2 H2 2021 AUTO6NG Neuroblastoma; Melanoma; GD2 H2 2021 Osteosarcoma;
Slide 33: AUTO6 designed to deliver anti-tumor activity without neurotoxicity
AUTO6 designed to deliver anti-tumor activity without neurotoxicity AUTO6: GD2-targeted programmed T cell therapy in neuroblastoma oProgrammed T cell product candidate: DAY 0 DAY 28 New binder design Minimize on-target, off-tumor toxicity Humanized to reduce immunogenicity RQR8 safety switch oPh
Slide 34: Modular approach designed to enhance AUTO6NG for solid tumor environment
Modular approach designed to enhance AUTO6NG for solid tumor environment Next generation programs powered by our proprietary technology toolbox GD2 CAR dnTGFβRII Receptor dSHP2 To provide anti-tumor activity To overcome inhibitory and potential to help address To overcome multiple effect of TGFβ in
Slide 35: AUTO6NG exhibits potent anti-tumor activity in preclinical model
AUTO6NG exhibits potent anti-tumor activity in preclinical model Extends survival in challenging in vivo model 1×10 10 PBS CONTROL AUTO6 1×10 9 CAR T-cells Total Flux AUTO6 1×10 8 PBS CONTROL 1×10 7 AUTO6 1×10 6 1×10 5 -1 2 7 10 14 Days after CART administration PBS CONTROL AUTO6NG 1×10 10 CAR T-cel
Slide 36: AUTO7 is designed to tackle the complex solid tumor environment
AUTO7 is designed to tackle the complex solid tumor environment Anti-PSMA humanized CAR T cell for improved persistence and resistance in Prostate Cancer SS-IL12 dnTGFβRII IL7R CCR α-PSMA CAR dSHP2 RapaCasp1 Immune PSMA CAR dnTGFβRII dSHP2 Cytokine signal Safety Switch Adjuvant Targeting of PSMA Tru
Slide 37: Manufacturing
Manufacturing 37
Slide 38: Economical & scalable product delivery platform
Economical & scalable product delivery platform Semi-automated and parallel processing Clinical supply & commercial launch o Multiple cell products can be processed within the same environment o CGT Catapult (UK) o Global clinical supply since Q3 2019 Planned US commercial supply o Collaboration wit
Slide 39: Next Steps
Next Steps 39
Slide 40: Multiple clinical milestones anticipated through 2021/2022
Multiple clinical milestones anticipated through 2021/2022 PRODUCT INDICATION TARGET PHASE NEXT MILESTONE AUTO1 Adult ALL CD19 Pivotal Ph1 long-term f/u, AL-1 data in 2022 Started Ph1 Q4 2020, first data Q4 AUTO1 /22 Pediatric ALL CD19/CD22 Phase 1 2021 Started Ph1 Q3 2020, data updates AUTO1 B-NHL
Slide 41: Autolus poised for potential value inflection
Autolus poised for potential value inflection oAUTO1 and AUTO1/22 Currently enrolling Autolus’ first Ph1b/2 pivotal program in adult ALL data expected in 2022 Granted orphan drug designation by the FDA for treatment of ALL Pediatric ALL—AUTO1/22 P1 started in Dec 2020, first data expected for Q4 202
Slide 42: Thank you
Thank you 42
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