Atara Biotherapeutics, Inc. · NASDAQ:ATRA
Atara Biotherapeutics — Q2 2020 Earnings Presentation
57 slides from Atara Biotherapeutics's earnings presentation, Aug 5, 2020
Slide 1: Investor Presentation
Ola EBV+ PTLD survivor Investor Presentation August 5, 2020 Nasdaq: ATRA CONFIDENTIAL 1
Slide 2: Forward-Looking Statements
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 1995. All statements other than statements of historical facts contained in this prese
Slide 3: Pioneering Off-the-Shelf, Allogeneic T-cell Immunotherapies
Pioneering Off-the-Shelf, Allogeneic T-cell Immunotherapies Mission to transform the lives of patients with severe diseases through pioneering science, teamwork and Doug PTLD champion a commitment to excellence Ola PTLD champion Ayden PTLD champion Jessica PTLD champion 1982-2019 Atara mourns the lo
Slide 4: Dedicated to Transforming the Lives of Patients
Dedicated to Transforming the Lives of Patients, Teamwork and a Commitment to Excellence: Atara Executive Team Pascal Touchon Jakob Dupont Joe Newell President and Head of Research and Chief Operations Officer Chief Executive Officer Development Kristin Yarema, Ph.D. AJ Joshi, M.D. Utpal Koppikar Ch
Slide 5: Most Advanced Allogeneic T-cell Company
Most Advanced Allogeneic T-cell Company Demonstrating the Feasibility of Delivering Off-the-Shelf T-Cell Immunotherapies to Patients • Clinically validated platform with over 300 patients treated • Favorable safety and efficacy profile in EBV-associated diseases Improving based on Atara and academic
Slide 6: Overview of Epstein-Barr Virus (EBV)
Overview of Epstein-Barr Virus (EBV) (1) Background EBV-associated diseases Present in >95% of individuals Infectious mononucleosis (mono) by age 40 Post transplant lymphoproliferative Persistent lifelong, disease (PTLD) asymptomatic infection Other hematologic malignancies: Infects B ce
Slide 7: EBV T Cells Offer Numerous Advantages
EBV T cells are Alpha Beta T cells that Offer Numerous Advantages as the Basis of an Allogeneic Platform SAFETY SAFETY Reduced ability to harm normal cells (GvHD) EXPANSION EXPANSION Proliferation with memory phenotype TRAFFICKING Homing and penetrating target lesions including solid tumors CYTOTOXI
Slide 8: Atara Allogeneic Platform Maintains Natural Biology
Atara Allogeneic Platform Maintains the Natural Biology of EBV T cells By Selecting the Most Appropriate HLA Alleles for a Patient We select product from inventory that shares a EBV TCR minimum of two HLA alleles with the patient — For EBV-associated diseases, one of the alleles must be the restri
Slide 9: Capability to Treat a Wide Range of Diseases
Atara Allogeneic Platform Has the Capability to Treat a Wide Range of EBV-Associated Diseases or Hematological / Solid Tumors Through an Engineered CAR or TCR EBV-associated Diseases Other Hematological or Solid Tumors EBV TCR EBV TCR CAR HLA HLA ATA3219 (Allo CD19) Tab-cel® ATA3271 (Allo MSLN
Slide 10: Atara Off-the-Shelf, Allogeneic EBV T-Cell Platform
Atara Off-the-Shelf, Allogeneic EBV T-Cell Platform SAFETY • Ability to modify with engineered CAR or TCR EXPANSION • Retreatment capability • Scalable bioreactor manufacturing • Proprietary cell selection and logistics • Delivery to patient from inventory in ~3 days • Global development and regulat
Slide 11: Atara Strategic Priorities to Create Value
Atara Strategic Priorities to Create Value Tab-cel® (tabelecleucel) PTLD Other EBV-associated malignancies ATA188 CAR T ATA2271/ATA3271 (Solid Tumors) Progressive Multiple Sclerosis ATA3219 (B-cell malignancies) Other CAR T 11
Slide 12: Robust T-Cell Immunotherapy Pipeline
Robust T-Cell Immunotherapy Pipeline Program Indication Target Preclinical Phase 1 Phase 2 Phase 3 Registration RR EBV+ PTLD following HCT EBV ALLELE Study RR EBV+ PTLD following SOT EBV ALLELE Study Tab-cel® (tabelecleucel) Multi-Cohort: EBV+ cancers(1) EBV Nasopharyngeal carcinoma(2) EBV ATA188 Pr
Slide 13: Dedicated State-of-the-Art T-Cell Manufacturing Capacity
Dedicated State-of-the-Art T-Cell Manufacturing Capacity Dedicated, expandable T-cell manufacturing facility in Thousand Oaks, CA Flexibility to produce multiple T-cell and CAR T immunotherapies Highly integrated cross-functional CMC support to enable rapid development Designed to meet globa
Slide 14: Manufacturing Platform Serve Us Well
The Design Principles Built Into Our Allogeneic Manufacturing ® Platform Serve Us Well As We Approach Tab-cel Commercial Launch Efficient Manufacturing We can serve >95% of patient population with ~40 strategically selected cell lines Our manufacturing process is robust Flexible Supply Chain A
Slide 15: Atara Strategic Priorities to Create Value: Tab-cel
Atara Strategic Priorities to Create Value Tab-cel® (tabelecleucel) Investigational T-cell immunotherapy for EBV-associated ultra-rare diseases FDA breakthrough designation and EMA PRIME for EBV+ PTLD ATA188 CAR T 15
Slide 16: EBV-Associated Post-Transplant Lymphoproliferative Disease
EBV-Associated Post-Transplant Lymphoproliferative Disease Aggressive, Often Deadly Cancer with No Approved Therapy Rare B-cell lymphoma that occurs in immunosuppressed patients after transplant Average age under 40 years vs. around 65 years for NHL — Bone marrow transplant (HCT) Ayden EBV+ PTLD r
Slide 17: Tab-cel Potential to Transform Treatment
Tab-cel® – Off-the-Shelf, Allogeneic T-Cell Immunotherapy with Potential to Transform Treatment of EBV+ PTLD NEW Week -10 Week -4 Week 0 Week 10 Week 15 Week 29 36-year-old with Increase in Disease Tab-cel® response: Continued Complete Fanconia anemia tumor burden progression after 3 rapid decrease
Slide 18: Ongoing Studies for Patients with EBV+ PTLD
Tab-cel® – Ongoing Studies for Patients with EBV+ PTLD Phase 2 and EAP ORR(1) Updated protocol for ongoing Phase 3 study(2) for EBV+ PTLD patients who failed rituximab — Global, multicenter, open-label 82% — Single Phase 3 study with two EBV+ PTLD patient cohorts (HCT and SOT) 69% — Approximately
Slide 19: Long-Term Outcomes for Patients with EBV+ PTLD
Tab-cel® – Long-Term Outcomes for Patients with EBV+ PTLD in Phase 2 and EAP Studies(1,2) Probability of Survival All, n=35, 1-yr OS=68.3% All, n=14, 1-yr OS=64.3% Probability of Survival Non Response, n=11, 1-yr OS=24.2% Non Response, n=7, 1-yr OS=28.6% 1.0 Response, n=24, (20CRs, 4PRs) 1-yr OS=87.
Slide 20: EBV+ PTLD – Attractive Ultra-Rare Disease Market
EBV+ PTLD – Attractive Ultra-Rare Disease Market Estimated Incidence in the U.S. in 2019(1) PTLD incidence Low single digits(2) Relapsed/refractory 40%-60% ~48,000 Allogeneic Several hundred transplants EBV+ PTLD patients SOT HCT who have failed ~80% ~20% rituximab ± chemo EBV+ HCT: ~100% SOT: ~60%
Slide 21: Compelling Value Proposition for EBV+ PTLD Patients
Tab-cel® – Compelling Value Proposition for EBV+ PTLD Patients and Healthcare System 50%-82% ORR in Phase 2 and EAP High and durable No CRS or >80% survival at treatment Excellent safety neurotoxicity observed 2 years in responders effect(1) profile(1) No treatment- No approved treatments related mo
Slide 22: Attractive Future Tab-cel Commercial Opportunity
Attractive Future Tab-cel® Commercial Opportunity Despite Current Clinical Study Constraints CLINICAL COMMERCIAL Potential transformative profile supports PTLD is an ultra-rare disease compelling value proposition Clinical study available at Expect ability to deliver to patients in ~10% of US transp
Slide 23: Proprietary Algorithm Used to Select Tab-cel from Inventory
Proprietary Algorithm Used to Select Tab-cel® from Inventory for Each Patient Based on Appropriate HLA Restriction and Allele RECOGNITION NO RECOGNITION NO RECOGNITION HLA and Antigen Match HLA Restriction Mismatch Antigen Restriction Mismatch T cell T cell T cell TCR TCR TCR EBV EBV Non- HLA HLA HL
Slide 24: Scalable EBV T-Cell Manufacturing
Scalable EBV T-Cell Manufacturing Single EBV+ donor leukopak yields ~400 tab-cel® doses(1) HETEROGENEOUS DONOR T CELLS EBV T CELL SELECTION AND EXPANSION EBV+ donor leukapheresis includes small T cells exposed to cells that present EBV antigens, population of T cells with EBV-specific TCR stimulatin
Slide 25: Potential to Benefit Other Patients with EBV-Driven Cancers
Tab-cel® Has the Potential to Benefit Other Patients with EBV-Driven Cancers Beyond Previously Treated EBV+ PTLD EBV-205 Phase 2 Study Design All Cohorts Include 1L Patients ENDPOINTS EBV+ PID LPD Additional Treatment Primary: Overall EBV+ AID LPD Response Rate (ORR) Quarterly EBV+ PTLD CNS End-of
Slide 26: EBV+ AID-LPD and EBV+ PID-LPD Cohorts
EBV+ AID-LPD and EBV+ PID-LPD Cohorts Represent the Largest Potential Patient Population of the Phase 2 Multi-Cohort Study Additional EBV+ LPDs (1L + 2L) Key Features 1 EBV+ AID-LPD 2 EBV+ PID-LPD • Largest potential patient In patients that are In patients that are population at a few thousand immu
Slide 27: EBV+ IA-LPDs Present a Meaningful Opportunity
EBV+ IA-LPDs(1) Present a Meaningful Opportunity to Expand Potential Tab-cel® Label U.S. Multi-Cohort Potential Label Expansion Populations – 2019(2) Disease incidence AID-LPD: low single digits IA-LPDs U.S. PID-LPD: high single digits Population at Risk ~205,000 Patients Potentially addressable pop
Slide 28: Atara Strategic Priorities: ATA188 for Progressive MS
Atara Strategic Priorities to Create Value ATA188 CAR T EBV T-cell immunotherapy for progressive multiple sclerosis (MS) 28
Slide 29: High Unmet Need Remains for Progressive MS
High Unmet Need Remains for Patient with Progressive MS ~2.3 million patients diagnosed and living with MS worldwide ~1 million MS patients worldwide have a progressive form of the disease (PMS) Continual clinical decline is expected Current treatments have seen only modest results in progre
Slide 30: MS Patients Underserved, Especially as Disease Progresses
MS Patients Underserved, Especially as Disease Progresses WW Diagnosed MS Patients Proportion of ~50% of Patients Remain Untreated Millions RRMS and PMS Patients 2.3 68% 61% 49% ROW 1.2 ~43% ~57% ~43% 41% PMS RRMS PMS EU5 0.6 US 0.5 Diagnosed MS Patients All MS RRMS SPMS PPMS Sources: Atara Analysis
Slide 31: Modest Efficacy Benefit from Current Treatment Options
Modest Efficacy Benefit from Current Treatment Options Active Secondary Progressive MS Primary Progressive MS 6-mth CDP Siponimod vs. Placebo in SPMS (EXPAND) 24-Wk CDP Ocrelizumab vs. Placebo in PPMS (ORATORIO) 26% 36% 20% 30% • Current therapies delay progression but do not fundamentally alter its
Slide 32: Growing Evidence that EBV Has a Major Role in MS
Growing Evidence that EBV Has a Major Role in the Pathogenesis of Multiple Sclerosis • Prior EBV infection is necessary for a patient to develop MS 1,4 • MS may be mediated by B cells that are infected with EBV 2 • Defective elimination of EBV-infected autoreactive B cells by CD8+ T cells results in
Slide 33: Auto-reactive EBV-Infected B Cells and Plasma Cells
Auto-reactive EBV-Infected B cells and Plasma Cells Normally Controlled by EBV T Cells Adapted from Pender MP. Neuroscientist 2011; 17:351-367. 33
Slide 34: What Could a Transformative Therapy in MS Look Like?
What Could a Transformative Therapy in MS Look Like? ILLUSTRATIVE Time EDSS = 0 (No Disability) Sustained reversal of disability Transformative advance Halted progression Disability Current treatments: ~6 month delay in progression EDSS = 10 (Death) Natural course of progression CONFIDENTIAL 34
Slide 35: Optimal Characteristics of a Progressive MS Treatment
Optimal Characteristics of a Progressive MS Treatment Safe and Halt or Penetrates Targets Addresses Well-tolerated Reverses CNS specific underlying disability B cells and biology progression plasma cells 35
Slide 36: What is ATA188?
What is ATA188? ATA188 is an off-the-shelf, allogeneic, EBV T-cell immunotherapy being studied in progressive forms of MS Off-the-shelf No Precision Two-hour Administered T cells pretreatment targeting to monitoring as an delivered required in the select EBV following outpatient antigens 5-10 minute
Slide 37: ATA188 Phase 1a Study with Ongoing Open-Label Extension
ATA188 Phase 1a Study with Ongoing Open-Label Extension Period will Allow Patients to be Retreated Annually Phase 1a Study Schema DOSE-ESCALATION (Year 1) OPEN-LABEL EXTENSION Cohorts 1–4, N = 6 per cohort (Years 2‒5) DLT PRIMARY ENDPOINTS Assessment Safety and identification of the DLT (35 Days) Pa
Slide 38: Definition of Outcome Criteria
Definition of Outcome Criteria (Clinical Response) Clinical Improvement1 Clinical Efficacy Criteria assessment with clinically significant improvement Partial Clinical Improvement2 Outcome Fatigue MS Impact Scale-29 T25FW5 9-hole peg test Criteria Severity Score (physical) -20% -20% -0.7 -8 Stable3
Slide 39: Sustained Disability Improvement Composite Scale
Sustained Disability Improvement Composite Scale Uses Both EDSS and Timed 25-Foot Walk Measures Outcome Definition • Disability improvement (DI) • Improvement in EDSS (≥1-point decrease compared with baseline ≤ 5, or ≥ 0.5-point decrease compared with baseline > 5); or Sustained Disability • Improve
Slide 40: Number of Patients Achieving SDI
ATA188 Phase 1a Data: Dose-Related Increase in Number of Patients/Cohort Exhibiting Sustained Disability Improvement in EDSS or T25FW Based on clinically significant 3 3 improvement in EDSS or T25FW Number of Patients Achieving SDI 6 months 12 months 2 2 2 40 1 1 1 1 These analyses include subjects
Slide 41: Number of Patients Achieving SDI
ATA188 Phase 1a Data: Dose-Related Increase in Number of Patients/Cohort Exhibiting Sustained Disability Improvement in EDSS Based on clinically significant 3 improvement in EDSS ONLY Number of Patients Achieving SDI 6 months 12 months 2 2 2 41 1 1 1 1 These analyses include subjects receiving all 6
Slide 42: Detail of Patients Experiencing Sustained Disability Improvement
Detail of Patients Experiencing Sustained Disability Improvement SDI was observed with and without prior history of anti CD20 in both PPMS and SPMS patients in cohorts 1-4 Subject Age / Gender MS Type Anti-CD20 Final Response BL EDSS Sustained Δ EDSS Sustained Δ T25FW Sustained Δ 9HPT (SDI) (3M, 6M,
Slide 43: Initiated the ATA188 Randomized, Placebo-Controlled Study
Atara has Initiated the ATA188 Randomized, Placebo-Controlled Study in at Least 36 Progressive MS Patients with an Adaptive Design Part 2 Study Schema DOUBLE-BLIND PERIOD OPEN-LABEL ENDPOINTS (Years 1 and 2) EXTENSION (Years 3‒5) CSF, blood – IgG, oligoclonal bands, ATA188 2 years of RNAseq, NFL R
Slide 44: Demonstrated Each Element of Our Platform
Atara Has Demonstrated Each Element of Our Platform to Support a Biologics-Like Supply Chain for ATA188 at Commercial Scale Data confirms we can scale up Current inventory model projects coverage manufacturing process into bioreactors of ~95% of MS patients with ~10 cell lines PRODUCTIVITY OF ONE LE
Slide 45: ATA188 A Bold Vision to Transform MS Therapy
ATA188 Precision targeting to select EBV antigens limits off-target A bold vision to activity transform MS therapy Off-the-shelf T cells delivered from inventory Phase 1 trial successfully demonstrated safety and No pretreatment required in the clinical trial protocol Two-hour monitoring following 5
Slide 46: Atara Strategic Priorities: CAR T
Atara Strategic Priorities to Create Value CAR T ATA2271/ATA3271 (Solid Tumors) ATA3219 (B-cell malignancies) Other CAR T 46
Slide 47: Novel Tool Kit of Technologies
We Have Assembled a Novel Tool Kit of Technologies Designed to Address Current CAR Limitations in the Field 1 Multi- Targeted 2 Next Gen 3 PD1 Dominant CARs Co-stimulatory domains Negative Receptor Methods of designing multi- Novel co-stimulatory domains Provide intrinsic checkpoint targeted CAR T c
Slide 48: Off-the-Shelf, Allogeneic CAR T Immunotherapy Strategy
Atara Off-the-Shelf, Allogeneic CAR T Immunotherapy Strategy Rapidly advance Invest autologous CAR T for in world-class T-cell proof-of-concept manufacturing Collaborate followed by off-the-shelf, with academic allogeneic EBV CAR Ts Leverage leaders applying T-cell research, development next-gen and
Slide 49: Exclusive License to Mesothelin-Targeted CAR T
Exclusive License to Mesothelin-Targeted CAR T Immunotherapy for Solid Tumors from MSK Mesothelin is an attractive target associated with aggressive solid tumors (1,2) Aberrant mesothelin expression promotes cancer cell proliferation and confers resistance to apoptosis — Associated with mesothelio
Slide 50: ATA2271 – Developing Autologous Mesothelin-Targeted CAR T
ATA2271 – Developing Autologous Mesothelin-Targeted CAR T Program in Solid Tumors with Partners at MSK Mesothelin is an attractive target associated with aggressive solid tumors that is supported by academic data MSLN ScFv Maintains ScFv that binds to mesothelin above cancer threshold Incorpor
Slide 51: Academic Off-the-Shelf, Allogeneic EBV CD19 CAR T Data
Academic Off-the-Shelf, Allogeneic EBV CD19 CAR T Data Gives High and Durable Response with R/R B-Cell Malignancies EBV T-cell platform has potential to generate off-the-shelf, allogeneic CAR T with high and durable responses EBV with low risk of toxicity(1) TCR CD19 Durable CR with median follo
Slide 52: ATA3219 – Potentially Best-In-Class CD19 CAR T Therapy
ATA3219 – Potentially Best-In-Class, Off-the-Shelf, Allogeneic CD19 CAR T Therapy 1 Off-the-shelf, allogeneic EBV T cell platform 2 Next-generation 3 Off-the-shelf CAR T CAR technologies with broad applications EBV EBV TCR TCR CD19 ScFv HLA HLA Novel 1XX costimulatory domain 52
Slide 53: Development of Off-the-Shelf, Allogeneic EBV CAR T
Atara Development of Off-the-Shelf, Allogeneic EBV CAR T Autologous – Mesothelin CAR T Clinical Proof-of-Concept MSLN ScFv MSLN ScFv Off-the-shelf, allogeneic EBV Mesothelin CAR T MSLN EBV ScFv TCR CD28 costimulatory 1XX costimulatory domain domain + PD-1 DNR MSK MSLN CAR T ATA2271 (NCT02414269, NCT
Slide 54: Atara CAR T Pipeline
Atara CAR T Pipeline – Applying Next-Generation Technologies in Collaboration with Academic Leaders Indication Target CAR T Technologies Autologous PD-1 DNR ATA2271 Solid tumors(1) Mesothelin 1XX co-stimulation Off-the-shelf, allogeneic PD-1 DNR ATA3271 Solid tumors(1) Mesothelin 1XX co-stimulation
Slide 55: Potential to Transform the Lives of Patients
Potential to Transform the Lives of Patients with Serious Diseases Tab-cel® ATA188 ATA2271 ATA3219 (tabelecleucel) ATA3271 SAFETY TRAFFICKING PERSISTENCE EXPANSION CYTOTOXICITY EBV T-CELL PLATFORM 55
Slide 56: Multiple Key Milestones Expected in 2020
Multiple Key Milestones Expected in 2020 Submitted clinical trial applications (CTA) to several European countries to enable opening EU clinical sites in 2020 Nov 2019 Tab-cel® Begin enrollment in a Phase 2 multi-cohort study including patients with other EBV+ cancers H2 2020 (tabelecleucel) Initiat
Slide 57: Thank You
ATARA BIO Thank You Nasdaq: ATRA
Atara Biotherapeutics — Q2 2020 Earnings Presentation on 6ix