Corporate Deck JP Morgan January 2019

Transcription

1 Corporate Deck JP Morgan 2019 January 2019

2 Disclaimer This presentation contains forward-looking statements, as that term is defined under the Private Securities Litigation Reform Act of 1995 (PSLRA), which statements may be identified by words such as believe, may, will, estimate, continue, anticipate, intend, expect and other words of similar meaning. These forward-looking statements involve certain risks and uncertainties. Such risks and uncertainties could cause our actual results to differ materially from those indicated by such forward-looking statements, and include, without limitation: the success, cost and timing of our product development activities and clinical trials; our ability to submit an IND and successfully advance our technology platform to improve the safety and effectiveness of our existing TCR therapeutic candidates; the rate and degree of market acceptance of T-cell therapy generally and of our TCR therapeutic candidates; government regulation and approval, including, but not limited to, the expected regulatory approval timelines for TCR therapeutic candidates; and our ability to protect our proprietary technology and enforce our intellectual property rights; amongst others. For a further description of the risks and uncertainties that could cause our actual results to differ materially from those expressed in these forward-looking statements, as well as risks relating to our business in general, we refer you to our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 6, 2018 and our other SEC filings. We urge you to consider these factors carefully in evaluating the forward-looking statements herein and you are cautioned not to place undue reliance on such forward-looking statements, which are qualified in their entirety by this cautionary statement. The forward-looking statements contained in this presentation speak only as of the date the statements were made and we do not undertake any obligation to update such forward-looking statements to reflect subsequent events or circumstances. We intend that all forward-looking statements be subject to the safe-harbor provisions of the PSLRA. 2

3 Pipeline progress in 2018 Proprietary pipeline Advancing through safety testing no evidence of off-target toxicity ADP-A2M4 (MAGE-A4) basket study: Cohorts 1, 2, and 3 ADP-A2M10 (MAGE-A10) triple tumor study: Cohorts 1, 2, and 3 ADP-A2M10 lung study: Cohorts 1, 2, and 3 ADP-A2AFP (AFP) Cohort 1: no hepatotoxicity observed; now in Cohort 2 In expansion phases (5B+) for all ADP-A2M4 and ADP-A2M10 studies NY-ESO Proof-of-concept program Response data in MRCLS (ASCO 2018) Synovial sarcoma update (SITC 2018) Cell dose and preconditioning matter Transitioned to GSK 3

4 Progress in 2018 building an integrated cell therapy company Clinical, cell manufacturing, and vector production Partnered for success >20 active sites at leading cancer centers in US, Canada, and EU Expanded collaboration with MD Anderson Cancer Center European infrastructure in place First patients enrolled in UK and Spain In-house cell manufacturing Navy Yard from first ever product to 10 patients per month capacity Scalable to ~100s of patients per year Routinely making >5 billion cell doses >90% success rate across a broad range of solid tumors CMC infrastructure Clinical infrastructure Securing vector supply Agreement for commercial vector supply from 3 rd party vendor Dedicated vector facility in place First production planned for

5 Patients treated by cohort Progress through 2018 ADP-A2M10 (MAGE-A10) ADP-A2M4 (MAGE-A4) ADP-A2AFP (AFP) Lung Triple tumor Multiple tumors HCC (liver) Cohort 1 5 * 3 * 3 2 Cohort In progress Cohort Expansion In progress 2 In progress 3 In progress - Total treated** * The only cohorts complete as of Jan 2018 ** As of 31 Dec 2018

6 Looking to the future 1H 2019 ADP-A2M10 and ADP-A2M4 - Accumulating more patient data in additional indications at target dose of 5B+ cells ADP-A2AFP - Continued dosing in Cohort 2 Full clinical update by Q1 call in May 2019 Pivotal study planning Continue progress with off-the-shelf program Beyond 2019 New targets into clinic Further next generation opportunities Off-the-shelf program into clinic 2H 2019 Durability data from ADP-A2M4 and ADP-A2M10 at target doses of 5B+ cells Dose escalation to Cohort 3 of ADP-A2AFP study Pivotal study initiated Commercial planning continues Next generation IND Combination study planned Manufacturing scalable to support pivotal trials 6

7 Our proprietary pipeline in solid tumors 7

8 Our proprietary pipeline SPEAR T-cell Target Indications Target dose (Cohort) 100 M (1) 1 BN (2) 5 BN (3) 5 BN+ (expansion) Registration studies ADP-A2M10 MAGE-A10 Non-small cell lung cancer (NSCLC) Bladder Melanoma Head &Neck ADP-A2M4 MAGE-A4 Bladder Melanoma Head & Neck Ovarian NSCLC Esophageal Gastric Synovial sarcoma MRCLS ADP-A2AFP AFP Hepatocellular carcinoma 8

9 Overview of study designs Target Indication Cohort Pre-conditioning # pts per protocol (# dosed) Target dose Per protocol range ADP-A2M4 (MAGE-A4) Urothelial Melanoma Head & Neck Ovarian NSCLC Esophageal Gastric Synovial sarcoma MRCLS Exp. [Cy (600 mg/m 2 /d) + Flu (30 mg/m 2 /d)] X 3d [Cy (600 mg/m 2 /d) + Flu (30 mg/m 2 /d)] X 3d [Cy (600 mg/m 2 /d)] x 3d + [Flu (30 mg/m 2 /d) X 4d] [Cy (600 mg/m 2 /d)] x 3d + [Flu (30 mg/m 2 /d) X 4d] 3-6 (3) 3-6 (3) 3-6 (3) up to 30 ([3] in progress) 100M 1B 5B 5B 60 to 120M 0.6 to 1.2B 1.2 to 6.2B 1.2 to 10B ADP-A2M10 (MAGE-A10) Urothelial Melanoma Head & Neck Exp. Lung Exp. [Cy (600 mg/m 2 /d) + Flu (30 mg/m 2 /d)] X 3d [Cy (600 mg/m 2 /d) + Flu (30 mg/m 2 /d)] X 3d [Cy (600 mg/m 2 /d)] x 3d + [Flu (30 mg/m 2 /d) X 4d] [Cy (600 mg/m 2 /d)] x 3d + [Flu (30 mg/m 2 /d) X 4d] [Cy (1800 mg/m 2 /d)] x 2d [Cy (600 mg/m 2 /d) + Flu (30 mg/m 2 /d)] X 3d [Cy (600 mg/m 2 /d)] x 3d + [Flu (30 mg/m 2 /d) X 4d] [Cy (600 mg/m 2 /d)] x 3d + [Flu (30 mg/m 2 /d) X 4d] 3-6 (3) 3-6 (0) 3-6 (4) Up to 10 ([2] in progress) 3-6 (5) 3-6 (3) 3-6 (2) Up to 10 (in progress) 100M 1B 5B 5B 100M 1B 5B 5B 60 to 120M 0.6 to 1.2B 1.2 to 6.2B 1.2 to 10B 60 to 120M 0.6 to 1.2B 1.2 to 6.2B 1.2 to 10B ADP-A2AFP (AFP) Hepatocellular carcinoma Exp. [Cy (500 mg/m 2 /d) + Flu (20 mg/m 2 /d)] X 3d [Cy (500 mg/m 2 /d) + Flu (20 mg/m 2 /d)] X 3d [Cy (500 mg/m 2 /d) + Flu (20 mg/m 2 /d)] X 3d [Cy (600 mg/m 2 /d)] x 3d + [Flu (30 mg/m 2 /d) X 4d] 3-6 (2) 3-6 (in progress) up to 6 Up to M 1B 5B 5B 60 to 120M 0.6 to 1.2B 1.2 to 5B 1.2 to 10B 9

10 Safety with SPEAR T-cells Patients treated with ADP-A2M10, ADP-A2M4, and ADP-A2AFP Most adverse events are consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies; similar to NY-ESO There has been one report of CRS Grade 3, thus far, or an incidence of ~3%; for all CRS (any grade) incidence is ~20%* Tolerability in patients treated has been acceptable, to date, and will allow for continued dose escalation and treatment in expansion phases SPEAR T-cells continue to show a promising benefit:risk profile for the patient populations in our trials 10 * As of Jan 2019

11 Becoming a fully integrated cell therapy company 11

12 Building a leader in T-cell therapy A bit of history 2006 Avidex acquired by Medigene Collaboration with NCI Collaboration with U-Penn Adaptimmune LLC is formed 2013 Complete response in synovial sarcoma with NY-ESO 2015 First IND opened on wholly owned program ADP-A2M10 IPO and NASDAQ listing Universal Cells collaboration 2017 GSK exercises option over NY-ESO and nominates PRAME as 2 nd target $62m raised via secondary public offering $42m raised via RDO to Matrix Capital Avidex formed on the basis of T-cell receptor technology from Oxford University 2008 Adaptimmune Ltd is created 2012 Exclusive license ThermoFisher for Dynabeads TM CD3/CD28 cell therapy system 2014 Collaboration with GSK on NY-ESO $104m raised via crossover round with US investors 2016 MD Anderson alliance Merck collaboration on NY-ESO + Keytruda combo Safety data with ADP-A2M10 & ADP-A2M4 / Dosing at >1 billion cells NY-ESO program transitioned to GSK ~$100m via RDO 12

13 Strong momentum towards our ambition Building a fully integrated cell therapy company Vector manufacturing Clinical testing Commercial TCR engineering Navy Yard HCATs (PCT) Regulatory Target identification In progress Target validation Catapult (UK) CMO network SPEAR T-cell manufacturing Pre-clinical testing 13

14 Adaptimmune today Our facilities and employees Stevenage (9 FTEs) Philadelphia, Navy Yard (161 FTEs) In-house GMP Vector Development & Production GMP Cell Manufacture Clinical, Regulatory Quality, Biometrics, Translational/CDx Corporate Functions Milton Park (250 FTEs) Corporate Functions (HQ) Research (Pipeline, Next Gen, Universal SPEAR-T cells Translational Science) Process Development 14 As of November 2018

15 Vector manufacturing Cell manufacturing Fully operational cell and vector manufacturing Integrated CMC capabilities for clinical development and commercial Pre-2016 Transitioned UPENN cell process to HCATs* Implemented process 1.5 (freeze at both ends) 2016 Dedicated cell manufacturing rooms at HCATs 2017 HCATs capacity to 10 patients per month Opened Navy Yard facility in US Routinely manufacture cells at target dose for a broad range of solid tumors Capacity for 20 patients per month between Navy Yard and HCATs Navy Yard scale out to 100s of patients per year Investment in ex-us cell manufacturing Pre-2016 Agreements with academic vector manufacturers Adaptimmune proprietary adherent vector process developed (v1.5) 2017 Initiated fit out of Catapult vector facility in UK 2018 Agreement for commercial vector supply from 3 rd party vendor 2019 Catapult facility operational with proprietary suspension vector process (v2.0) 15 * Formerly PCT

16 Global technology network: partnering with industry leaders Building the future of T-cell therapy through world-class expertise Clinical Platform development Manufacturing (HCATs) 16

17 Adaptimmune SPEAR T-cell studies at leading clinical centers Building the future of T-cell therapy through world-class expertise Palo Alto UCLA 17

18 SPEAR T-cell platform 18

19 Cell therapy has become mainstream Harnessing the immune system to fight cancer August 2017 Gilead acquires Kite ($11.9bn) October 2017 FDA approval of Yescarta January 2018 Celgene acquires Juno (~$9bn) January 2019 BMS acquires Celgene (~$76bn) Takeda establishes cell therapy unit August 2017 September 2017 GSK options NY-ESO December 2017 BlueBird presents BCMA data February 2018 Gilead deal with Sangamo ($3bn) FDA approval of first CAR-T treatment (Kymriah) 19

20 Engineering T-cells T-cell receptors (TCR) vs. synthetic receptors (CAR)

21 Many natural affinity TCRs do not recognize tumors Affinity enhancement is required for optimal recognition of non mutational tumor antigens Affinity No TCR Natural affinity Enhanced affinity TCR candidates No reactivity Cross reactivity TCR binds the target in correct HLA? Representative ELISPOT data from cells displaying antigen target (AFP + ) in correct HLA context (A2 + ) Is TCR cross-reactive? Representative ELISPOT data from cells displaying antigen target (AFP + ) in incorrect HLA (A2 neg ); or without target (AFP neg ) in correct HLA (A2 + ) 21

22 Identifying targets and developing optimized SPEAR T-cell therapies A systematic process Dedicated target validation program Generate TCRs for any target Proprietary technology to affinity optimize SPEAR T-cells Target identification Molecular database screens and literature Confirmation of protein expression Mass spec validation of processed peptides in HLA Multiple methods for TCR identification / generation Optimal specificity Overcomes naturally occurring low TCR affinities Can target solid tumors Mass spec. >1.2 million peptides in our database Screened for alloreactivity 22

23 Lessons and data from NY-ESO program (partnered with GSK) 23

24 NY-ESO clinical trials GSK now holds the IND for NY-ESO 99 patients in six cancer indications PROGRAM INDICATIONS PRE-CLINICAL PHASE I / II REGISTRATION Synovial sarcoma NY-ESO Fully enrolled MRCLS NSCLC (lung) NY-ESO + Keytruda Enrolling Multiple myeloma 24

25 Lessons from NY-ESO in soft-tissue sarcomas Informing study designs across all programs SPEAR T-cells migrate to and infiltrate cold tumors Recruiting other inflammatory cells Responses in two distinct solid tumors with NY-ESO Synovial sarcoma and myxoid/ round cell liposarcoma (MRCLS) Including patients with low NY-ESO expressing tumors Reducing large tumor burdens SPEAR T-cell expansion correlates with response Cell dose matters - 1 billion + cells required for response Preconditioning matters - more intense fludarabine regimen leads to higher response rate and duration NY-ESO SPEAR T-cells show promising benefit:risk profile Improved understanding of regulatory agency expectations for development / pivotal programs 25

26 SPEAR T-cells migrate to and infiltrate cold tumors Recruiting other inflammatory cells 26

27 Change from baseline (%) Change from baseline (%) Change from baseline (%) Responses in two distinct solid tumors with NY-ESO Synovial sarcoma: responses in all cohorts including low expressors (CTOS 2017) Cohort 1 Cohort 2 Hi NY-ESO, Hi Flu/Cy ORR= 50%; N=12 Low NY-ESO-1,Flu/Cy ORR=22%; N=9 Cohort 3 Hi NY-ESO-1,Cy ORR=20%; N=5 Months Cohort 4 Hi NY-ESO, Mod Flu/Cy ORR=27%; N=11 Months 27

28 Cell dose and preconditioning regimen matter More intense fludarabine regimen leads to higher response rate and duration Cohort 1 Hi NY-ESO-1 Hi Flu/Cy N=12 Cohort 2 Lo NY-ESO-1 Hi Flu/Cy N=10 Cohort 3 Hi NY-ESO-1 Cy N=5 Cohort 4 Hi NY-ESO-1 Mod Flu/Cy N=14 ORR: Confirmed, CR + PR: N (%) 6 (50) 4 (40) 1 (20) 4 (29) Best overall response: N (%) CR PR SD PD Not assessed 1 (8) 5 (42) 6 (50) 0 (0) 0 (0) 0 (0) 4 (40) 4 (40) 1 (10) 1 (10) 0 (0) 1 (20) 4 (80) 0 (0) 0 (0) 0 (0) 4 (29) 9 (64) 2 (5) 1 (2) Median Duration of Response (DoR): weeks (range) 30.9 (13.6, 72.1) 8.5 (9.9, 12.9) 32.0 (32.0, 32.0) (9.0, 27.0) 28

29 Responses in two distinct solid tumors with NY-ESO Reducing large tumor burdens (synovial sarcoma) Baseline Month 6 29

30 Solid financial position

31 Strong balance sheet: Runway to late 2020 Enables delivery of data from ADP-A2M10, ADP-A2M4, and ADP-A2AFP $238 million LIQUIDITY * Through late 2020 FUNDS current business operations 31

32 Corporate Deck JP Morgan 2019 January 2019