Cowen Healthcare Conference

Transcription

1 Ola EBV+ PTLD survivor Cowen Healthcare Conference March 12, 2019 Isaac Ciechanover, M.D. Chief Executive Officer & President Nasdaq: ATRA 1

2 Forward-Looking Statements This presentation and the accompanying oral presentation contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, product candidates, regulatory approvals, the initiation, timing, progress and results of preclinical studies and clinical trials and our research and development programs, ability to sell, manufacture or otherwise commercialize our product candidates, research and development costs, timing and likelihood of success, plans and objectives of management for future operations, any royalty payments, and our ability to obtain and maintain intellectual property protection for our product candidates, are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These forward-looking statements are subject to risks and uncertainties, including those discussed in Atara Biotherapeutics' filings with the Securities and Exchange Commission (SEC), including in the Risk Factors and Management s Discussion and Analysis of Financial Condition and Results of Operations sections of the Company s most recently filed periodic reports on Form 10-K and Form 10-Q and subsequent filings and in the documents incorporated by reference therein. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Certain information contained in this presentation and statements made orally during this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and Atara's own internal estimates and research. While Atara believes these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of Atara s internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research. The content of this presentation is subject to copyright, which will be asserted by Atara and no part of this presentation may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without prior permission in writing from Atara. 2

3 Strong Recent Execution on Our Objectives Tab-cel Pipeline Advanced Phase 3 studies for patients with EBV-associated post-transplant lymphoproliferative disorder (PTLD) Initiated a Phase 1b/2 study in combination with KEYTRUDA for patients with EBV-associated nasopharyngeal carcinoma (NPC) Added next-generation and off-the-shelf, allogeneic CAR T immunotherapies including collaborations with academic leaders Expanded off-the-shelf, allogeneic ATA188 Phase 1 study for patients with progressive MS Corporate Expanded R&D, operational and commercial leadership Opened state-of-the-art T-cell operations and manufacturing facility Strengthened cash position to fund operations to mid

4 Innovative Off-the-Shelf, Allogeneic T-Cell Platform EBV-specific T cells from healthy donors Next-generation CAR T technologies World-class T-cell manufacturing Atara MatchMe TM HLA matching and logistics 4

5 World-Class T-Cell Manufacturing Here Today Dedicated, expandable ATOM (Atara T-cell Operations & Manufacturing) facility in Thousand Oaks, CA Flexibility to produce multiple T-cell and CAR T immunotherapies Integrated research and process science to enable rapid development and leverage research collaborations Designed to global regulatory standards (completing licensure for clinical production) 5

6 Pioneering Off-the-Shelf, Allogeneic T-Cell Immunotherapies Three major near-term value creation opportunities Tab-cel (tabelecleucel) Multiple sclerosis Next-gen CAR T 6

7 Robust T-Cell Immunotherapy Pipeline Indication/Program Target Preclinical Phase 1 Phase 2 Phase 3 Registration RR EBV+ PTLD following HCT EBV MATCH Tab-cel (tabelecleucel) RR EBV+ PTLD following SOT Nasopharyngeal carcinoma (1) EBV EBV ALLELE EBV+ cancers (2) EBV Multiple sclerosis Autologous ATA190: Progressive MS Off-the-shelf, allogeneic ATA188: Progressive MS EBV (3) EBV (3) Solid tumors (4-6) Mesothelin Next-gen CAR T Acute myeloid leukemia (4) B-cell malignancies (4) Off-the-shelf, allogeneic B-cell malignancies Dual undisclosed CD19-CD20- CD22 CD19 RR: rituximab relapsed/refractory; Other programs: ATA230 (CMV), ATA368 (HPV), ATA520 (WT1) and ATA621 (BK/JCV) (1) Phase 1b/2 study in combination with anti-pd-1 therapy, KEYTRUDA (pembrolizumab), in patients with platinum-resistant or recurrent EBV-associated NPC. (2) Phase 2 basket study planned including EBV+ LMS, EBV+ PTLD with CNS involvement and other EBV+ cancers (3) Targeted antigen recognition technology (4) Development expected to start in autologous setting (5) Mesothelin is expressed at high levels on the surface of cells in aggressive solid tumors including mesothelioma, triple-negative breast cancer, esophageal cancer, pancreatic cancer and non-small cell lung cancer (6) MSK investigator-sponsored Phase 1 study (NCT ) of a mesothelin-targeted CAR T immunotherapy is ongoing; Atara s CAR T collaboration with MSK will focus on development of a next-generation, mesothelin-targeted CAR T using novel 1XX CAR signaling and PD-1 dominant negative receptor (DNR) checkpoint inhibition technologies. 7

8 Pioneering Off-the-Shelf, Allogeneic T-Cell Immunotherapies Three major near-term value creation opportunities Tab-cel (tabelecleucel) Multiple sclerosis Next-generation CAR T EBV-associated cancers FDA breakthrough designation & EMA PRIME for EBV+ PTLD Developing first T-cell immunotherapy outside of oncology Novel signaling, multi-targeted & intrinsic checkpoint inhibition Off-the-shelf, allogeneic EBV+ PTLD: Epstein-Barr virus-associated post-transplant lymphoproliferative disease 8

9 Epstein-Barr Virus (EBV) The Original Oncovirus Background Present in >95% of individuals by age 40 Persistent lifelong, asymptomatic infection Infects B cells and epithelial cells Implicated in a wide range of cancers and autoimmune diseases EBV-associated diseases Infectious mononucleosis (mono) Post transplant lymphoproliferative disorder (PTLD) Other hematologic malignancies: PID/AID-related lymphomas Nasopharyngeal carcinoma (NPC) Other solid tumors: leiomyosarcoma, gastric cancer Growing evidence for role in the pathogenesis of multiple sclerosis (MS) Young LS, Rickinson AB. Nat Rev Cancer Oct;4(10): PID/AID-related lymphomas: EBV+ primary immunodeficiency lymphoproliferative disease (EBV+ PID LPD), EBV+ acquired immunodeficiency-associated LPD (EBV+ AID LPD) 9

10 EBV-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) Rare B-cell lymphoma that occurs in immunosuppressed patients after transplant Aggressive cancer that often rapidly progresses to death after diagnosis Bone marrow transplant (HCT) post-transplant risk up to recovery of immune system (~1 year) Solid organ transplant (SOT) chronic post-transplant risk due to immunosuppression Current therapeutic strategy rituximab ± chemotherapy High mortality rituximab relapsed/refractory patients HCT: allogeneic hematopoietic cell transplant Fox CP, et al. Bone Marrow Transpl. 2014;49(2): ; Uhlin M, et al. Haematologica. 2013;99(2): ; Choquet S, et al. Ann Hematol. 2007;86: ; Gonzolaz-Barca E, et al. Haematologica. 2007;92(11): ; Styczynski J, et al. Clin Infect Dis. 2013;57(6): ; Ocheni S, et al. Bone Marrow Transplant. 2008;42(3):

11 Potential to Transform Treatment of Rituximab Relapsed/Refractory EBV+ PTLD NEW Week -10 Week -4 Week 10 Week 15 Week 0 Week year-old with Fanconia anemia diagnosed with EBV+ PTLD Increase in tumor burden Disease progression after 3 cycles of rituximab Tab-cel response: rapid decrease of tumor burden Expected survival after rituximab failure: days in EBV+ PTLD following HCT (1) Continued decrease of tumor burden Complete response (CR) after 4 cycles of tab-cel Prockop S, et al. Proc AACR 2015; 36 year-old woman with Fanconi anemia; Radiographic results from Phase 2 clinical study patient provided for illustrative purposes only to show how the clinical parameters above may correlate to the clinical presentation of a patient. (1) Expected median survival for patients with EBV+ PTLD following HCT who have failed rituximab first line therapy is 16 to 56 days; Atara estimated 1-year survival based on analysis of Ocheni S, et al. EBV reactivation and post transplant lymphoproliferative disorders following allogeneic SCT. Bone Marrow Transplantation Aug;42(3):181-6; Fox CP, et al. EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: Clinical features, viral load correlates and prognostic factors in the rituximab era. Bone Marrow Transplant. 2014;49(2):

12 Tab-cel Off-the-Shelf, Allogeneic T-Cell Immunotherapy with Compelling Therapeutic Advantages Available in ~3 days with T cells delivered from inventory No pretreatment required Precision EBV targeting to limit offtumor toxicity Two-hour monitoring following short IV infusion 12

13 Tab-cel Multicenter EAP Results for Patients with EBV+ PTLD Observed overall response rates for patients who failed rituximab (1) 80% 83% Phase 3 design (2) Global, multicenter, open-label 35 patients per indication 37% ORR primary Phase 3 endpoint threshold (3) N = 5 N = 6 HCT SOT EAP: Expanded Access Protocol; HCT: allogeneic hematopoietic cell transplant; SOT: solid organ transplant; Overall response rate (ORR) = complete response (CR) + partial response (PR) (1) Prockop, S., et al. ASH 2017; Multicenter EAP findings from the Phase 3 populations (2) MATCH: EBV+ PTLD following HCT after failure of rituximab (N=35); ALLELE: EBV+ PTLD following SOT after failure of rituximab (N = 35) and after failure of rituximab + chemo (N = 35); Cohorts enroll concurrently and are not comparative; Treatment regimen: 2x106 cells/kg weekly for 3 wks followed by 2 wks rest. (3) The protocols are designed to rule out 20% ORR as the null hypothesis. For example, assuming anticipated enrollment of 35 patients in MATCH, an ORR above approximately 37% would be expected to meet the primary endpoint. In ALLELE, each of two cohorts with an anticipated enrollment of 35 patients will be analyzed independently using the same statistical methodology. 13

14 Tab-cel Phase 2 Study Positive Long-Term Outcomes for Patients with EBV+ PTLD HCT Probability of Survival SOT Probability of Survival Censored Overall Survival Time (Months) Number at Risk (Event): All, n=35, 1-yr OS=68.3% Non Response, n=11, 1-yr OS=24.2% Response, n=24, (20CRs, 4PRs) 1-yr OS=87.5% Median All 35 (0) 26 (9) 23 (11) 18 (14) 17 (14) 14 (14) 13 (15) 12 (15) 6 (15) 3 (15) 3 (15) Non Response 11 (0) 4 (7) 2 (8) 0 (10) Response 24 (0) 22 (2) 21 (3) 18 (4) 17 (4) 14 (4) 13 (5) 12 (5) 6 (5) 3 (5) 3 (5) Censored All, n=14, 1-yr OS=64.3% Non Response, n=7, 1-yr OS=28.6% Response, n=7, (2CRs, 5PRs) 1-yr OS=100% Median Overall Survival Time (Months) Number at Risk (Event): All Non Response Response 14 (0) 9 (5) 9 (5) 7 (7) 7 (7) 6 (8) 6 (8) 6 (8) 4 (8) 4 (8) 2 (9) 7 (0) 2 (5) 2 (5) 1 (6) 1 (6) 1 (6) 1 (6) 1 (6) 1 (6) 1 (6) 0 (7) 7 (0) 7 (0) 7 (0) 6 (1) 6 (1) 5 (2) 5 (2) 5 (2) 3 (2) 3 (2) 2 (2) Overall survival at 1 year 68% Overall response rate 69% Median survival not yet reached (1) Overall survival at 1 year 64% Overall response rate 50% Median survival of 21.3 months Few treatment-related serious adverse events (SAEs): 12 possibly related Serious Adverse Events (SAEs) among 173 patients: no infusion related toxicities, no CRS (cytokine release syndrome) and three possibly related graft vs. host disease (GvHD); Safety data on file as of December Prockop, S., et al. EHA (1) after 23.3 months of follow-up 14

15 Tab-cel Compelling Value Proposition in EBV+ PTLD High and durable response data (1) Off-the-shelf Costeffective therapy (2) Few treatmentrelated serious events 10%-15% pediatric population Low cost of administration (1) Prockop S, et al., Proc ASCO 2015 (2) Atara data on file. Initial Atara valuebased assessment. (3) Franke AJ, et al. Proc. ASCO 2017 Potential to minimize risk of graft loss (3) Repeat dosing & cell line switching 15

16 Tab-cel for EBV-Associated Metastatic Nasopharyngeal Carcinoma (EBV+ NPC) Head & neck cancer that is primarily EBV-associated No approved targeted agents Standard treatment: platinum-based chemo ± targeted therapy 5-11 months median overall survival with standard treatment (1) Encouraging tab-cel Phase 1 monotherapy results in metastatic/2l+ NPC (2) 21% ORR Few treatment-related SAEs 84% 2-year overall survival Initiated Phase 1b/2 study in combination with KEYTRUDA (1) Ma, et al. Cancer Sci Jul;99(7):1311-8; Hsu OncLive conference coverage, 2015 European Cancer Congress (2) Prockop, S, et al., Proc ASCO 2016; 21% ORR includes one complete response and two partial responses 16

17 Tab-cel Pipeline in a Product EBV+ PTLD Phase 3 initial top-line results in H EBV+ NPC Initiated Phase 1b/2 with KEYTRUDA EBV+ cancers Phase 2 basket study planned 17

18 Pioneering Off-the-Shelf, Allogeneic T-Cell Immunotherapies Three major near-term value creation opportunities Multiple sclerosis Next-generation CAR T Developing first T-cell immunotherapy outside of oncology Novel signaling, multi-targeted & intrinsic checkpoint inhibition Off-the-shelf, allogeneic 18

19 Growing Evidence that EBV Has a Major Role in the Pathogenesis of Multiple Sclerosis Loss of EBV-specific CD8+ T-cell function correlates with MS disease progression Increased limitation in walking ability Walking aid (1 side) required Normal neurological exam 2.0 Minimal disability 3.0 Significant disability Restricted to wheelchair Bedridden Death Adapted from: (1) MS risk Increases sharply following EBV infection; Levin LI, et al. Ann Neurol Jun;67(6): (2) Moreno MA, et al. Neurol Neuroimmunol Neuroinflamm (4):e466. (3) Pender MP. Neuroscientist 2011; 17: (4) Kuhle J, et al. Multiple Sclerosis Journal (8):

20 B-Cell Targeted Treatment for Progressive MS: Major Achievement, Slows Disability Progression Ocrelizumab Phase 3 PPMS study (1) Cumulative probability of 24-week disability progression (%) 10%-15% of PPMS patients expected to have worsening of EDSS at 24 weeks PPMS: Primary Progressive Multiple Sclerosis (1) Montalban et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med Jan 19;376(3): doi: /NEJMoa Epub 2016 Dec 21; Median EDSS

21 Autologous ATA190 Demonstrated Encouraging Results in 10 Patients with Progressive MS Well tolerated Patients with no treatmentrelated serious adverse events observed 26 weeks: 6 weeks of treatment and 20 weeks of F/U (1) Patients experienced improvement Patients experienced both symptomatic and objective neurological improvement (2) Strong ATA190 EBV reactivity Patients received ATA190 with strong EBV reactivity and experienced clinical improvement Encouraging EDSS results Reduction in fatigue was a consistent observation in responding patients 3 Patients improved EDSS score (3) (1) Pender MP, et al. Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis. JCI Insight Nov 15;3(22). pii: doi: /jci.insight (2) Improvements commence 2-14 weeks after initial treatment (3) EDSS improvement in 3 patients: 5 to 4.5, 5 to 3.5 and 6.5 to 6; 10%-15% of PPMS patients expected to have worsening of EDSS at 24 weeks (Montalban et al NEJM) 21

22 Off-the-shelf, Allogeneic ATA188 Phase 1 Study Design for Patients with Progressive MS Multicenter, open-label study ongoing in the U.S. and Australia Objectives Enrollment Treatment Endpoints Safety and tolerability Clinical activity Recommended phase 2 dose SPMS and PPMS patients EDSS (1) Off MS therapy Progressive dose cohorts 1 year follow-up Dose selection and expansion phase after final dose cohort completed Safety EDSS (2) MRI (3) Other clinical activity measures Biomarkers (1) Subjects with EDSS scores of 6.5 to 7.0 must retain measurable upper limb function as assessed by the 9-Hole Peg Test (2) Change from baseline in expanded disability status scale (EDSS) score (3) Change from baseline in the number of Gd-enhancing and new or enlarging T2 lesions on magnetic resonance imaging (MRI) scans 22

23 Realizing the Potential of EBV-Targeted T-Cell Immunotherapy for Multiple Sclerosis ATA190 autologous Randomized Phase 2 study to start in H ATA188 off-the-shelf, allogeneic Initial safety results expected in H1 2019; Additional results anticipated in H

24 Pioneering Off-the-Shelf, Allogeneic T-Cell Immunotherapies Three major near-term value creation opportunities Next-generation CAR T Novel signaling, multi-targeted & intrinsic checkpoint inhibition Off-the-shelf, allogeneic 24

25 Atara s Next-Generation CAR T Immunotherapy Strategy Rapidly advance CAR T programs using established targets with clinical proof-of-concept Collaborate with academic leaders applying next-gen technologies Invest in world-class T-cell manufacturing Leverage T-cell research, development and regulatory experience 25

26 Atara Next-Generation and Off-the-Shelf, Allogeneic CAR T Approach EBV-specific off-the-shelf, allogeneic T cell platform Next-generation CAR technologies Off-the-shelf CAR T with broad applications 26

27 Developing Multi-Targeted CAR T Immunotherapies for AML and B-Cell Malignancies T cell Antigen Activated T cell Dual-targeted CAR T with AND gate Acute Myeloid Leukemia (AML): Initial application Avoid targeting of healthy tissues expressing only one target (on-target, off-tumor toxicity) Normal cell Cancer cell Multi-targeted CAR T with OR gate B-cell malignancies: CD19-CD20-CD22 Overcome antigen loss resistance Hanada K, Restifo NP. Double or nothing on cancer immunotherapy. Nat Biotechnol Jan;31(1):

28 Exclusive License to Mesothelin-Targeted CAR T Immunotherapy for Solid Tumors from MSK Mesothelin is an attractive target associated with aggressive solid tumors Aberrant mesothelin expression promotes cancer cell proliferation and confers resistance to apoptosis Associated with mesothelioma, triple-negative breast cancer and non-small cell lung cancer (1,2) Mesothelin-associated cancers (1) Incidence: ~340,000 patients Prevalence: ~2 million patients (1) Morello A, Sadelain M, Adusumilli PS. Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors. Cancer Discov Feb;6(2):133-46; U.S. incidence/prevalence. (2) Frequency and distribution pattern of the mesothelin protein in solid malignancies. 28

29 Mesothelin-Targeted CAR T + PD-1 Checkpoint Inhibitor April 2017 Nov year-old with unresectable biphasic mesothelioma Complete metabolic response (CMR) after CAR T + PD-1 Initial results from ongoing MSK Phase 1 study for mesothelin-targeted CAR T (NCT ) Of the 6 patients treated with CAR T cells following preconditioning cyclophosphamide plus PD-1 One durable complete metabolic response (CMR) Two partial responses (PR) One stable disease (SD) Well tolerated with no adverse events greater than Grade 2 and no on-target, off-tumor toxicity Unique scfv binds to Mesothelin antigen only above cancer threshold, avoiding off-tumor toxicity Basis for next-generation, mesothelin-targeted CAR T using novel 1XX signaling domain and PD-1 DNR technologies Adusumilli PS, et al. A phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CART cells: safety and efficacy - a preliminary report. Abstract 342; 2018 ASGCT Annual Meeting; Chicago, IL; May 16-19, PET CT results from ongoing MSK Phase 1 study (NCT ) patient provided for illustrative purposes only to show how the clinical parameters above may correlate to the clinical presentation of a patient 29

30 Next-Generation CAR T Oncology Pipeline Expanding with Novel Technology Collaborations Program Indication Target CAR T Technologies Collaborator ATA2271 Solid tumors (1) Mesothelin PD-1 DNR Novel 1XX co-stimulation (2) ATA2321 AML Dual-targeted undisclosed Novel co-stimulation (2) ATA2431 B-cell malignancies CD19-CD20- CD22 Novel co-stimulation (2) ATA3219 B-cell malignancies CD19 Off-the-shelf, allogeneic Novel co-stimulation Rapidly advancing four next-generation CAR T oncology programs with at least one IND expected Q to Q AML: acute myeloid leukemia; DNR: Dominant Negative Receptor (1) Mesothelin is expressed at high levels on the surface of cells in aggressive solid tumors including mesothelioma, triple-negative breast cancer, esophageal cancer, pancreatic cancer and non-small cell lung cancer (2) Development expected to start in autologous setting 30

31 Multiple Key Milestones Expected in 2019 Tab-cel (tabelecleucel) Multiple sclerosis Next-gen CAR T FDA and EMA regulatory discussions to align on a global regulatory strategy for patients with EBV+ PTLD EU conditional marketing authorization submission planned for patients with EBV+ PTLD who failed first-line therapy Initial top-line EBV+ PTLD results following submission of the EMA CMA application Initial results expected from off-the-shelf, allogeneic ATA188 study for patients with progressive MS Initiate randomized autologous ATA190 study for patients with progressive MS Announced exclusive license to next-generation mesothelintargeted CAR T immunotherapy for solid tumors from MSK Submit first IND for next-generation CAR T H H H H1 & H H January 2019 Q to Q

32 Transforming the Lives of Patients with Serious Medical Conditions Tab-cel (tabelecleucel) Multiple sclerosis Next-generation CAR T Pioneering off-the-shelf, allogeneic T-cell immunotherapies Leading academic collaborations & cutting-edge technologies World-class T-cell manufacturing 32

33 Nasdaq: ATRA Thank you Ayden EBV+ PTLD survivor 33