Q1 2024 Financial Results and Business Updates 17 May 2024 Autolus.com
Disclaimer 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 in some cases can be identified by terms such as “may,” “will,” “could,” “expects,” “plans,” “anticipates,” and “believes.” These statements include, but are not limited to, statements regarding Autolus’ development of its product candidates, including the obe-cel program; the profile and potential application of obe- cel in additional disease settings; the future clinical development, efficacy, safety and therapeutic potential of the Company’s product candidates, including progress, expectations as to the reporting of data, conduct and timing and potential future clinical and preclinical activity and milestones; expectations regarding the initiation, design and reporting of data from clinical trials and preclinical studies; the extension of the pipeline beyond obe-cel; expectations regarding the regulatory approval process for any product candidates; the benefits of the collaboration between Autolus and BioNTech, including the potential and timing of milestone payments and royalties under the terms of the strategic collaboration; the Company’s current and future manufacturing capabilities; and the Company’s anticipated cash runway. Any forward-looking statements are based on management’s current views and assumptions and involve risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in such statements. These risks and uncertainties include, but are not limited to, the risks that Autolus’ preclinical or clinical programs do not advance or result in approved products on a timely or cost effective basis or at all; the results of early clinical trials are not always being predictive of future results; the cost, timing and results of clinical trials; that many product candidates do not become approved drugs on a timely or cost effective basis or at all; the ability to enroll patients in clinical trials; and possible safety and efficacy concerns. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Autolus’ actual results to differ from those contained in the forward-looking statements, see the section titled “Risk Factors” in Autolus' Annual Report on Form 10-K filed with the Securities and Exchange Commission, or the SEC, on March 21, 2024, as well as discussions of potential risks, uncertainties, and other important factors in Autolus’ subsequent filings with the Securities and Exchange Commission. All information in this presentation is as of the date of the presentation, and Autolus undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law. You should, therefore, not rely on these forward-looking statements as representing the Company’s views as of any date subsequent to the date of this presentation. Developing Next Generation Programmed T Cell Therapies 2
Agenda 3 Developing Next Generation Programmed T Cell Therapies • Welcome and Introduction: Olivia Manser, Director, Investor Relations • Operational Highlights: Dr. Christian Itin, CEO • Financial Results: Rob Dolski, CFO • Upcoming Milestones and Conclusion: Dr. Christian Itin, CEO • Q&A: Dr. Christian Itin and Rob Dolski
Autolus executed to plan in Q1 2024 Developing Next Generation Programmed T Cell Therapies 4 Clinical Operational • Obe-cel progressed according to plan – BLA accepted with a PDUFA target date of November 16 – MAA accepted by EMA end of Q1 – Commercial and clinical license received by MHRA for Nucleus manufacturing facility – Two patients enrolled in SLE Phase 1 CARLYSLE study; first trial site activated in Q1 • Oral presentations confirmed for ASCO and EHA – Longer f/u for FELIX study – Impact of stem cell transplant – Impact of obe-cel persistence on outcome • Additional poster presentations at EHA – Impact of inotuzumab-based bridging therapy – Sensitive methods for CAR T persistency measurements • Strategic BioNTech collaboration: $200m equity, $50m cash upfront • Underwritten registered direct offering: $350m gross proceeds • New board members: Mike Bonney (Chair), Ravi Rao, Bob Azelby, Lis Leiderman
Obe-cel pooled analysis ASH 2023 FELIX Phase 1b/2 trial
Reliable obe-cel supply for FELIX despite the COVID–19 pandemic Developing Next Generation Programmed T Cell Therapies 6 1United States Department of Transportation, Bureau of Transportation Statistics 2021 [online]. Available at: https://www.bts.gov/data-spotlight/commercial-aviation-2020-downturn-airline-passengers-employment-profits-and-flights Accessed October 2023; 2World Health Organization COVID–19 dashboard [online]. Available at: https://covid19.who.int/ Accessed October 2023 • US international airline flights decreased by 41% compared to flights from pre-COVID–19 pandemic1 • BUT international flights are reliable and on time • Sample collection and drug product delivery were successfully maintained, with no batches impacted Ph1b Start PhII Start
FELIX Phase 1b/2 pooled analysis: patient disposition Developing Next Generation Programmed T Cell Therapies 7 127/153 (83%) enrolled patients received obe-cel* *Seven patients received Dose 1 only; **All eligibility criteria met and the leukapheresate accepted for manufacturing; obe-cel, obecabtagene autoleucel; Roddie et al., ASH 2023, Data cut-off date: September 13, 2023; ***Morphologic disease defined as ≥5% BM blasts or presence of EMD regardless of BM blast status; ‡MRD status available for 64/73 patients, as assessed by NGS or flow cytometry; §MRD status available for 27/29 patients, as assessed by NGS or flow cytometry; BM, bone marrow; CR, complete remission; CRi, CR with incomplete hematologic recovery; EMD, extramedullary disease; MRD, measurable residual disease; NGS, next-generation sequencing; obe-cel, obecabtagene autoleucel Discontinued n (%) 26 (17) Death 15 (10) Manufacturing-related 7 (5) Adverse event 2 (1) Physician decision 1 (0.7) Progressive disease 1 (0.7) Infused N = 127 (83%) Enrolled** N = 153 Cohort A n = 107 (84%) ≥5% BM blasts at screening Cohort B n = 13 (10%) MRD-positive at screening Cohort C n = 7 (6%) Isolated EMD at screening 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 patients were MRD-negative§
FELIX Phase 1b/2 pooled analysis: EFS in all treated patients* • Median follow-up time was 16.6 months (range: 3.7−36.6 months) • 17/99 (17%) responders proceeded to SCT while in remission Developing Next Generation Programmed T Cell Therapies 8 The event-free survival estimate at 12 months was 50% *Censoring new non-protocol anti-cancer therapies including SCT with disease assessment by IRRC (data cut-off date: September 13, 2023); Median EFS: ITT population − 9.8 months (95% CI: 5.9, 12.9); CI, confidence interval; EFS, event-free survival; IRRC, Independent Response Review Committee; ITT, intent-to-treat; NE, not evaluable; obe-cel, obecabtagene autoleucel; SCT, stem cell transplant; Roddie et al., ASH 2023 Events, n: Overall Median (95% CI): Overall 59 11.7 (7.2, NE) P ro b ab ili ty ( % ) 0 10 20 30 40 50 60 70 80 90 100 Time (months) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 Overall (N = 127) Patients at risk 127 104 94 85 78 68 60 55 52 45 34 33 29 27 27 22 18 18 16 12 12 6 5 4 4 4 3 3 3 3 2 2 2 2 2 2 1 0 All treated patients (N = 127) Median EFS (95% CI), months 11.7 (7.2, NE) 6-month EFS (95% CI), % 65 (56, 73) 12-month EFS (95% CI), % 50 (39, 59)
FELIX Ph1b/2 pooled: EFS by leukemic burden prior to lymphodepletion* Developing Next Generation Programmed T Cell Therapies 9 Lower leukemic burden is associated with better outcomes *Censoring new non-protocol anti-cancer therapies including SCT with disease assessment by IRRC (data cut-off date: September 13, 2023); BM, bone marrow; CI, confidence interval; EFS, event-free survival; IRRC, Independent Response Review Committee; NE, not evaluable; SCT, stem cell transplant; Roddie et al., ASH 2023 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, 82) 40 (23, 56) 12-month EFS (95% CI), % 65 (44, 80) 55 (38, 69) 27 (12, 44) Events, n: <5% 10 ≥5−≤75% 22 >75% 27 Median (95% CI): <5% NE ≥5−≤75% 15 (6.6, NE) >75% 4.5 (1.5, 9.0) Patients at risk <5% (n = 36) ≥5−≤75% (n = 51) >75% (n = 40) <5% (n = 36) ≥5−≤75% (n = 51) >75% (n = 40) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 36 34 31 28 25 24 22 20 19 18 14 13 11 11 11 11 8 8 7 6 6 2 2 2 2 2 1 1 1 1 1 1 1 1 1 1 0 0 51 43 41 39 36 31 28 25 23 18 15 15 13 12 12 9 8 8 7 4 4 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 40 27 22 18 17 13 10 10 10 9 5 5 5 4 4 2 2 2 2 2 2 2 2 1 1 1 1 1 1 1 0 0 0 0 0 0 0 0 Time (months) 0 10 20 30 40 50 60 70 80 90 100 P ro b ab ili ty ( % )
FELIX Phase 1b/2 pooled analysis: CRS and ICANS • No grade ≥3 CRS and/or ICANS were observed in patients with <5% BM blasts at lymphodepletion • Vasopressors were used to treat CRS in 2.4% of patients • The treatment was generally well tolerated • Two deaths were considered treatment-related per investigator assessment: neutropenic sepsis (n = 1); acute respiratory distress syndrome and ICANS (n = 1) Developing Next Generation Programmed T Cell Therapies 10 Low rates of Grade ≥3 CRS and/or ICANS were observed BM, bone marrow; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; ICU, intensive care unit; Roddie et al., ASH 2023 BM blasts % at lymphodepletion 2% 7% 20 0 40 60 80 100 In ci d e n ce , % CRS ICANS 0% 4% 3% 20 0 40 60 80 100 In ci d e n ce , % <5% ≥5−≤75% >75% 0% 6% 15% 20 0 40 60 80 100 In ci d e n ce , % <5% ≥5−≤75% >75% CRS and ICANS in all patients CRS by % BM blasts ICANS by % BM blasts Light colors = grade ≤2 Dark colors = grade ≥3 69% 23% 47% 69% 88% 8% 18% 43%
Commercial Launch Readiness
Commercial Readiness Obe-cel steps to commercialization 12 Roadmap to a commercial launch in r/r adult ALL Obe-cel BLA accepted by FDA Nucleus MHRA inspection & approval Obe-cel EMA MAA Developing Next Generation Programmed T Cell Therapies FDA PDUFA Target FDA Action Date November 16 Obtained MHRA MIA together with accompanying GMP certificate Q1 Q2 Q3 Q4 Medical affairs engagement Value and HEOR evidence generation US Center onboarding US supply chain, logistics and systems testing Obe-cel MHRA authorization application Filing of MHRA marketing authorization application (MAA) planned for H2 2024
The Nucleus – Our Commercial Manufacturing Facility • ~70,000 sq ft facility • Modular build using PAMs • 70% built off-site • 60% reduced build time • BREEAM Excellent rating for sustainability • Designed for 2,000+ batches per year • Target vein to delivery time 16 days at launch Developing Next Generation Programmed T Cell Therapies 13 State of the art design and operations established – groundbreaking to complete validation in 2 years Design Build Operations Nov 8, 2021 Groundbreaking Nov 25, 2022 First clean room operational May 2023 Capacity challenge 2021 2022 2023 2024 Dec 14, 2022 First Prodigy operational 2H 2023 Facility validation complete Q1 2024 MHRA GMP certificate
Expanding the obe-cel opportunity Deep value program with potentially broad applicability
The obe-cel product family and franchise opportunity Developing Next Generation Programmed T Cell Therapies 15 Obe-cel CD19 AUTO1/22 CD19/CD22 AUTO8 CD19/BCMA B-ALL and B-NHL B-cell mediated autoimmune disease B-ALL and B-NHL Multiple Myeloma B-cell and plasma cell mediated autoimmune • Optimized 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 • Dual CD19 & CD22 Targeting • Designed to prevent antigen negative escape • Supported by Phase 1 data in pediatric B-ALL • Dual CD19 & BCMA Targeting • Designed to induce deep and durable responses • Initial Phase 1 data presented at ASH 2023
Dynamic environment in cell therapy for autoimmune patients Developing Next Generation Programmed T Cell Therapies 16 Thoughts on clinical data from compassionate use and limited clinical trial experience *Cantor Fitzgerald research note April 29, 2024 • Available clinical data is largely based on compassionate use experience, not clinical trials • A Kymriah-like autologous CAR T program showed transformational clinical outcomes in refractory autoimmune patients – To date a single myositis patient relapsed after 18 months (compassionate use cohort) • With T cell engagers (TCE), initial experience with blinatumomab with experimental c.i.v. administration resulted in clinical improvement, without eliminating the B cell compartment fully – "T cell engagers did not appear to drive deep/durable remissions beyond treatment and as such would require chronic therapy", Georg Schett* • Redosing in autoimmune patients may be challenging due to the risk of immunogenicity of CAR T and s.c. administered T cell engager products
• Erlangen CD19 CART was developed for treating paediatric ALL – CD19 CAR is identical to Kymriah – Manufacturing modified from Kymriah – Initial data shown in paediatric ALL patients at ASH 2021 in line with data from Kymriah • Obe-cel has a modified design to reduce immunological toxicity compared to Kymriah • Obe-cel experience in pediatric and adult ALL confirm differentiated profile – High level of molecular complete remissions – Lasting responses – Similar persistence of CART cells – Reduced immunological toxicity (CRS, ICANS) 17 Systemic Lupus Erythematosus (SLE) and autoimmunity: a new space for CAR T Obe-cel is similar to Erlangen CD19 CART Differentiated CD19 engagement (fast off-rate) Off Rate: Kd [S-1] ]1 - S 1 - [M a K : e Ra t - On Other CD19 Binders Obe-cel Binder Off Rate: Kd [S-1] O n -R at e: K a [M -1 S- 1 ] Shorter half-life of interaction compared to binders used in approved products • obe-cel = 9.8 seconds (CAT) • Kymriah® = 21 minutes (FMC63) CARPALL1 FELIX2 FELIX2 low disease burden ELIANA3 Indication Pediatric Adult Adult Pediatric n 14 127 29 75 ORR 86% 78% 100% 83% 12mth EFS 54% 50% 65% 50% CRS any Grade 93% 69% 47% 77% CRS > Grade 3 0% 2% 0% 48% ICANS any Grade 50% 23% 8% 71% ICANS > Grade 3 7% 7% 0% 22% 1. Ghorashian et al., Nature Medicine 2019 2. Roddie et al, ASH 2023 3. USPI 2023, Maude et al., NEJM 2018 Low disease burden defined as <5% bone marrow blast at lymphodepletion obe-cel Kymriah
Phase 1 study in r/r SLE – open for enrollment CARLYSLE Study • A Single-Arm, Open-Label, Phase I Study to Determine the Safety, Tolerability and Preliminary Efficacy of Obecabtagene Autoleucel in Patients with Severe, Refractory Systemic Lupus Erythematosus (SLE)* Study details • Number of patients: 6 (option to add further cohort of 6 patients) • Primary endpoint: to establish the tolerability and safety of obe-cel in patients with severe, refractory SLE • Secondary endpoints: to evaluate the preliminary efficacy of obe-cel using measures of SLE disease activity • Dosing: 50 x 106 CD19 CAR-positive T cells • Follow up: up to 12 months • First two patients enrolled; initial clinical data expected in late 2024 Developing Next Generation Programmed T Cell Therapies 18 Primary goal of the Phase 1 study will be confirming the fixed dose in adult SLE patients * A Study of CD19 Targeted CAR T Cell Therapy in Patients With Severe, Refractory Systemic Lupus Erythematosus (SLE) – Full Text View – ClinicalTrials.gov Autoimmune
Other pipeline programs and technologies A broad portfolio of potential next generation modular T cell therapies
Autolus pipeline Developing Next Generation Programmed T Cell Therapies 20 Product Indication Target Study Name Partner Phase Status/Expected Milestones Obe-cel Adult B-ALL CD19 FELIX Pivotal Submitted to EMA and FDA (PDUFA November 16, 2024) Obe-cel Systemic Lupus Erythematosus CD19 CARLYSLE Phase 1 Initial data late 2024 Obe-cel B-NHL and CLL CD19 ALLCAR19 UCL Phase 1 Data in peer reviewed journal Obe-cel PCNSL CD19 CAROUSEL UCL | Phase 1 Data in peer reviewed journal AUTO1/22 Pediatric ALL CD19 & CD22 CARPALL UCL * Phase 1 Data in BLOOD August 2023 AUTO8 Multiple Myeloma CD19 & BCMA MCARTY Phase 1 Updated clinical data in H2 2024 * BioNTech holds an option to co-fund and co-commercialize Obe-cel product family Product Indication Target Study Name Partner Phase Status/Expected Milestones AUTO4 TRBC1+ Peripheral TCL TRBC1 LibrA T1 Phase 1 Data in peer reviewed journal AUTO5 TRBC2+ Peripheral TCL TRBC2 – Preclinical Data in peer reviewed journal AUTO6NG Neuroblastoma GD2 MAGNETO UCL | BioNTech * Phase 1 Study open for enrollment AUTO9 Acute Myeloid Leukemia CD33, CD123 & CLL1 TBD UCL Preclinical Estimated Phase 1 start 2025 Additional pipeline programs Oncology Autoimmune
Financial Results
Financial summary (unaudited) USD Q1 2024 ($ '000) Q1 2023 ($ '000) Variance ($ '000) License revenues 10,091 1,292 8,799 R&D (30,671) (27,388) (3,283) G&A (18,177) (9,284) (8,893) Loss on disposal of property and equipment - (3,768) 3,768 Total operating expense, net (38,757) (39,148) 391 Other (expense) income, net (1,605) 782 (2,387) Interest Income 6,933 3,446 3,487 Interest expense (19,269) (4,905) (14,364) Income tax benefit 8 14 (6) Net loss after tax (52,690) (39,811) (12,879) Q1 2023 ($ '000) Q4 2023 ($ '000) Variance ($ '000) Cash and cash equivalents 758,529 239,566 518,963 Building a fully integrated, next-generation CAR T company 22
Upcoming news flow
Autolus planned news flow Developing Next Generation Programmed T Cell Therapies 24 Anticipated Milestone or Data Catalysts Anticipated Timing Obe-cel FELIX data update at ASCO, EHA & ASH 2024 June & December 2024 Obe-cel Marketing Authorization Application to MHRA Second half 2024 Obe-cel U.S. FDA PDUFA target action date November 16, 2024 Obe-cel in autoimmune disease – initial data from SLE Phase 1 study Late 2024
Autolus.com Thank you