Isaac Ciechanover, MD Founder, President, & CEO

Transcription

1 Isaac Ciechanover, MD Founder, President, & CEO Jefferies Global Healthcare Conference June 3, 2015 Proprietary Materials

2 Special Note Regarding Forward-Looking Statements This presentation and the accompanying oral presentation contain forward-looking statements. 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, collaborations, regulatory approvals, the possible impact of accelerated approval and whether the receipt of breakthrough therapy designation will meaningfully impact review by the U.S. Food and Drug Administration or the likelihood that a product will be found to be safe and effective, our ability to sell, manufacture or otherwise commercialize our product candidates, research and development costs, the 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 and other important risk factors are described more fully in documents filed by Atara with the Securities and Exchange Commission (SEC), including Atara s annual report on Form 10-K for the year ended December 31, 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 Foundation Built on World-Class Science Sep 2012 License Sep 2014 Option TGF-β family protein modulators Seven product candidates Clinical Stage Programs T-cell immunotherapies Platform to develop additional product candidates PINTA 745 Ph 2 STM 434 Ph 1 T-cell EBV¹ Ph 2 T-cell CMV² Ph 2 T-cell WT1³ Ph 1 ¹ EBV = Epstein-Barr virus ² CMV = cytomegalovirus ³ WT1 = Wilms tumor 1 3

4 PINTA 745 PINTA 745 Protein-Energy Wasting in End-Stage Renal Disease (ESRD) 4

5 PINTA 745: Potential First in Class Molecule for PEW Phase 2 Program with Established Proof of Concept (POC) PINTA 745 Blocks myostatin, preventing it from inhibiting muscle production Improved lean body mass, physical function, inflammation in CKD¹ model Statistically significantly increased lean body mass and lower extremity muscle size in randomized, blinded Phase 1 study in prostate cancer; acceptable safety Attractive Market PEW state of muscle wasting, inflammation, malnutrition in ESRD; no approved therapies Decreased physical function, increased morbidity and mortality ~250K patients in US² and 800K worldwide Upcoming Milestone Randomized, blinded, placebo controlled Phase 2 trial (48 PEW patients) Phase 2 data expected in 4Q:15 ¹ CKD = chronic kidney disease ² Calculated utilizing 2011 data from USRDS extrapolated to December 31, 2013 as well as data from the recent study completed with DaVita Clinical Research 5

6 Clinical POC in Patients with Prostate Cancer Receiving ADT¹ PINTA 745 Lean Body Mass Increase Lower Extremity Muscle Size Increase 8% N = % N = % 10% % of Baseline 4% 2% 0% (2)% (4)% % of Baseline 8% 6% 4% 2% 0% (2)% (4)% P=0.065 P=0.007 (6)% (6)% EOS FUP 3.0 mg/kg PINTA 745 Placebo 3.0 mg/kg PINTA 745 Placebo ~2% greater in lean body mass at EOS Difference in lean body mass compared to placebo continued to increase in 4 weeks after treatment (FUP) At EOS, muscle size increased by ~1.2% from baseline At FUP, the change from baseline increased to 2.7% Source: Padhi et al., Pharmacological inhibition of myostatin and changes in lean body mass and lower extremity muscle size in patients receiving androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab 99(10):E1967 Note: The bottom and top of the boxes represent the first and third quartiles, and the horizontal band inside the box indicates the median value. The ends of the whiskers represent the minimum and maximum data in the range of observations Note: EOS: end-of-study (at day 29); FUP: Follow-up Period (one month after day 29) ¹ ADT = androgen deprivation therapy 6

7 Increased Mortality in Patients with PEW PINTA 745 Survival Rates Based Upon Serum Albumin Levels 100% 80% Percentage Surviving 60% 40% 20% Results at one year: ~11% of PEW¹ patients died within one year compared to < 3% of non- PEW patients At three years: ~40% of PEW patients died in comparison with ~21% of non-pew patients 0% Days from Entry into Database Serum Albumin 3.8 g/dl Serum Albumin > 3.8 g/dl 54% of dialysis patients suffer from PEW 1 Large unmet need; ~250,000 2 US; ~800,000 Worldwide 1 Based on a recent study we completed with DaVita Clinical Research, a division of DaVita Healthcare Partners Inc. 2 Calculated utilizing 2011 data from USRDS extrapolated to December 31, 2013 as well as data from the recent study completed with DaVita Clinical Research 7

8 Preclinical Proof of Concept in CKD Mice PINTA 745 Ctrl CKD Received from William E. Mitch, Baylor College of Medicine, M.D. Myostatin is Over-Expressed in CKD Mice and PINTA 745/s Has a Demonstrated Ability to Increase Body Weight ¹ Synthesis (nmol Phe/g/hr) * * P<0.05 Placebo PINTA 745/s Degradation (nmol Tyr/g/hr) Placebo * P<0.05 * PINTA 745/s pg / ml TNF - α IL - 6 P=0.033* P=0.036* Placebo PINTA 745/s Placebo PINTA 745/s pg / ml Increase Protein Synthesis ¹ Limit Protein Degradation ¹ ¹ Based on a preclinical study conducted with Amgen (Zhang L & Mitch WE, FASEB J. 2011) and Reduce Inflammation¹ 8

9 Ongoing Phase 2 Trial in ESRD Patients with PEW Phase 2 Data Expected 4Q:15 PINTA 745 Randomized, double-blind, placebo-controlled trial in 48 patients Primary endpoint change in muscle mass Secondary endpoints physical function, monitoring of inflammatory markers, effects on use of supportive care drugs, QOL¹ assessments Clinical Update Phase 2 Trial in ESRD Patients with PEW No treatment-related serious adverse events, grade 3 adverse events Initial regimen safe and well tolerated Study enrollment ongoing ¹ QOL = Quality of Life 9

10 MSK Collaboration 10

11 Atara MSK Collaboration Overview Pathway to Commercialization Sponsored Research Ongoing and Planned POC Studies Allogeneic, cellular therapy platform technology developed by MSK Exclusive Option to license 3 clinical T-cell programs targeting some viral or cancer antigens Collaborate on further research to discover additional cellular therapies Leverage existing technology to target other antigens Develop additional cellular therapies and / or CAR-T cell programs 11

12 Platform Attributes Off-the shelf cellular therapeutic option for patients EBV - CTLs Manufacturing process designed to reduce risk of product-related GvHD¹ MSK has developed libraries of EBV, CMV, and WT1 activated cell lines MANUFACTURE 1 T-cells from Donor Blood 2 Antigen exposure, expansion and characterization 3 Targeted T- cell Banks THERAPEUTIC USE Cancer or Viral Infection Blood Test: HLA² Typing Off-the-shelf T-cell Doses 1 GvHD = graft versus host disease ² HLA = human Leukocyte Antigen 12

13 Targeted T-Cell Therapy for EBV-LPD after HCT Current Treatment Approach EBV - CTLs If Rituximab Failure EBV Reactivation: Lymphoma EBV-LPD Standard Rx: e.g., Rituximab Rituximab (anti-cd20 Ab) is often used off-label as 1 st line therapy; Off-the-shelf EBV-Targeted T-cell Doses Historical survival in rituximab refractory patients median days 1 Time Course of a Complete Response Following Administration of EBV Targeted T-cell 2 ¹ Prockop, S et al., Proc AACR (2015), Fox 2014, Ocheni 2008, Uhlin MSK Data on file 13

14 Clinical Experience with EBV-CTL in EBV-LPD EBV - CTLs Two separate clinical trials of EBV-CTL conducted by MSK Study Primary HCT and 3 rd party donor derived EBV-CTL Study rd party donor derived EBV-CTL Includes EBV-LPD after HCT and solid organ transplant (SOT) Results in EBV-LPD after HCT presented in a Clinical Trials Plenary session at AACR 2015 (April 19, 2015) Results in EBV-LPD after SOT presented at ASCO 2015 (June 1, 2015) 14

15 Clinical POC in EBV-LPD after HCT: Phase 2 Study Results¹ Response Rate (RR): Primary vs. 3 rd party Donor EBV-CTL Source N Prior Rituximab RR 2 DCR 2 EBV - CTLs 2015 ASCO Presentation Overall Survival: Rituximab Refractory Patients Treated with 3 rd party EBV-CTL Study Primary Donor % 69% 3 rd Party Donor % 70% 1 year OS = 71.8% 2 year OS = 63.8% N = 22 RR with primary HCT and 3rd party donor comparable RR in rituximab treated patients similar to overall RR Complete and partial responses were durable & led to the overall survival results observed Well tolerated, few serious related AEs; no cytokine release, 1 grade 1 GvHD resolved without systematic therapy Historical survival in rituximab refractory patients median days ¹ Prockop, S et al., Proc AACR (2015), Prockop, S et al., Proc ASCO (2015), Based on results from two clinical trials of EBV-CTL conducted by MSK 2 RR = complete response + partial response; DCR = Disease control rate = complete response + partial response + stable disease 3 Prockop, S et al., Proc AACR (2015) 4 Prockop, S et al., Proc ASCO (2015), Includes 22 patients from Study plus 11 patients from Study plus one patient treated under a treatment IND Study year OS = 56.3% 2 year OS = 46.9% N = 12 15

16 EBV-CTL: EBV-LPD after SOT 2nd Indication¹ EBV-CTL Source Response Rate (RR): EBV-LPD after SOT N Prior Rituximab Prior Chemo RR 2 3 rd Party Donor % Note: All patients had failed to respond or relapsed following rituximab treatment; 11 SOT recipients also progressed after 1-5 courses of rituximab and chemotherapy OS in Rituximab Refractory EBV-LPD after SOT following treatment with 3rd party EBV-CTL Results Response Rate (RR) for SOT of 62% is similar to RR for HCT 1 durable CR (>22mo) and 7 durable PRs (range: mo) in heavily pre-treated patients 12 of the 13 patients had high risk disease 3 (Age 60 years; poor performance status; elevated LDH) Overall Survival (OS) of 58% at 2 years compares favorably with historical data Historical Data 3 Historical data show 33% OS at 2 years in patients with incomplete response to rituximab Historical data show 0% OS at 2 years in patients with high risk disease ¹ Prockop, S et al., Proc ASCO (2015), Based on results from two clinical trials of EBV-CTL conducted by MSK 2 RR = complete response + partial response 3 Choquet et al.,

17 Phase 2 Clinical POC in antiviral resistant CMV after HCT¹ CMV - CTLs Current Treatment Approach If Treatment Failure or Intolerance CMV Reactivation: Viremia or Disease CMV Standard Rx: e.g., Ganciclovir or Foscarnet Off-the-shelf CMV-Targeted T-cell Doses Responses Following Administration of CMV Targeted T-cells Viremia Only 2 CMV Disease 3 25 Evaluable Patients 9 Complete Responses 7 Partial Responses 9 Evaluable Patients 5 Complete Responses 1 Partial Responses Response Rate = 64% Response Rate = 67% Interim data presented at ASH 2014; No de novo GvHD or flare of pre-existing GvHD was noted ¹ Prockop, S et al., Proc ASH (2014), MSK (data on file) 2 Responses in patients treated for viremia alone were considered complete if the viremia resolved completely and partial if it fell by more than 100-fold 3 Responses in disease were considered complete if all detectable CMV viremia and disease resolved and partial if patients became asymptomatic 17

18 STM 434 STM 434 Ovarian Cancer and Other Solid Tumors 18

19 STM 434: Potential First in Class Molecule for Ovarian Cancer and Other Solid Tumors STM 434 Phase 1 Program with Pre-clinical POC Inhibits Activin A, which is involved in proliferation of OC and other solid tumor Reduced tumor size as single agent and with chemotherapy preclinically Demonstrated efficacy in granulosa / clear cell preclinical models of OC Gene mutations in FOXL2 and ARID1A link Activin to granulosa and clear cell OC, respectively Attractive Market Opportunity for rapid development in difficult-to-treat clear and granulosa cell OC Expansion opportunities in serous OC and other solid tumors ~22K new OC cases in 2013 in the US 1 Upcoming Milestone 3 part Phase 1 ongoing including dose escalation, dose expansion, chemo combo Initial Phase 1 data expected 1H:16 ¹ National Cancer Institute estimate 19

20 Pre-clinical POC in Granulosa Cell Ovarian Tumors STM 434 Suppressed Tumor Growth Improvement in Survival 1 Normal Control Treated with Placebo Ovarian Tumor Size Inhibin Knockout Treated with Placebo Inhibin Knockout Treated with STM 434/s Right Left FOXL2 granulosa cell tumor gene linkage 2 In normal cells, FOXL2 protein turns on follistatin when activin signal received; shuts off activin signal In granulosa cell OC, mutant FOXL2 is not able to turn on follistatin; activin signals unchecked Mutation was present in 97% of granulosa cell tumors ¹ Zhou X, et al. Cell. 2010; 142(4): Shah S. P., et al. NEJM. 2009; 360:

21 Pre-clinical POC in Clear Cell Ovarian Tumors STM 434 Significant Reduction in Tumor Volume¹ Enhanced Body Weight¹ ARID1A clear cell tumor gene linkage 2 ARID1A mutations drive upregulation in signaling cascade triggered by ActR2B receptor Mutations present in 46%-55% of ovarian clear cell tumors Increased activin levels, like ARID1A mutations, may contribute to clear cell tumor proliferation ¹ Lu J, Haqq C, & Han HQ. ASCO Annual Meeting (2013) 2 Wiegard., et al. NEJM. 2010; 363:

22 Ongoing First-in-Human (Phase 1) Study First Patient Dosed 10/14; Initial Data Readout Expected 1H:16 STM 434 Dose Escalation in Solid Tumors Monotherapy Dose Expansion in OC Combo Chemotherapy in OC Three part open-label Phase 1 study in up to 66 patients Objectives include: Evaluate whether STM 434 is safe and well tolerated Obtain preliminary efficacy data in ovarian cancer and other solid tumors Explore biomarkers predictive of response to treatment Define recommended Phase 2 dose 22

23 Multiple Opportunities for Value Creation Validated Clinical Programs Attractive Markets PINTA 745: Myostatin inhibitor for protein-energy wasting (PEW) MSK T-Cell Programs: Option to license T-cell platform technology with 3 clinical stage, off-the-shelf, immune therapies; Breakthrough Therapy Designation granted in February 2015 for EBV-CTL in patients with EBV-LPD STM 434: Activin inhibitor for ovarian cancer and solid tumors PEW: Increased morbidity / mortality; ~250K patients in the US¹ and 800K worldwide; no approved therapeutics EBV-LPD (~1200 patients in US + EU³) and anti-viral drug resistant CMV viremia or disease (~1100 patients in US + EU 4 ); potentially rapid path to approval Ovarian Cancer (OC): One of the deadliest cancers in women in the US; ~22K new cases in 2013 in the US 2 ; expansion opportunities in other solid tumors Upcoming Milestones PINTA 745: Phase 2 data in 4Q:15 EBV-CTL: Data presented at AACR Clinical Trials Plenary April 19, 2015 Oral presentation at ASCO June 1, 2015 MSK T-cell Programs: Data submitted to multiple conferences in 2015 STM 434: Phase 1 data in 1H:16 ¹ Calculated utilizing 2011 data from USRDS extrapolated to December 31, 2013 as well as data from the recent study completed with DaVita Clinical Research ² National Cancer Institute estimate ³ Atara estimate based on the CIBMTR reports of number of HCT in the US in 2011 and a report in the journal Haematologica (2013) 4 Atara estimate based on investigator experience 23

24 June 2015