Corporate Presentation. January 2019

Transcription

1 Corporate Presentation January

2 Safe Harbor and Forward Looking Statements Special Note Regarding Forward-Looking Statements This presentation contains forward-looking statements including, but not limited to, statements related to our preclinical and clinical product candidates, GRANITE, SLATE, and its bispecific antibody program. All statements other than statements of historical facts contained in this presentation, including statements regarding timing of regulatory submissions and clinical trial initiation for SLATE-001, timing of early data for GRANITE-001, identification of development candidate for our bispecific antibody program, our future results of operations and financial position, business strategy, prospective products, availability of funding, clinical trial results, product approvals and regulatory pathways, timing and likelihood of success, plans and objectives of management for future operations, and future results of current and anticipated products, are forward-looking statements. Because forward-looking statements are inherently subject to 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. 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. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the company in general, see Gritstone s period filings with the Securities and Exchange Commission, including its most recent Quarterly Report on Form 10-Q for the period ended September 30, 2018 filed on November 14, 2018 and any current and periodic reports filed thereafter. 2

3 Corporate Highlights Clinical-stage Company Developing Next- Generation Immunotherapies for the Treatment of Cancer Therapies Combine Two Powerful Proprietary Technologies: Initiated Phase 1 GRANITE-001 Study; Collaboration with BMS for checkpoint inhibitors EDGE TM artificial intelligence model for neoantigen and other tumor antigen prediction Immunotherapy platform utilizing two viral vectors to prime and boost immune system Proof of concept in non-human primates where profound T cell responses were observed Clinical program focused on indications with incomplete responses to available IO therapies IND Submission for SLATE-001 Planned for Mid-2019 Platform Versatility Enables Multiple Potential Product Candidates Foundational Excellence Personalized GRANITE program & off-the-shelf SLATE program Advancing bispecific antibody program into lead optimization phase Broad TCR discovery platform enables partnerships for cellular therapies, such as with bluebird bio Cash position of ~$173M* Strong foundational IP In-house manufacturing capabilities *Based on 3Q reported cash of $77.4M and net proceeds from IPO of $95.6M 3

4 Gritstone Oncology (Nasdaq: GRTS) at a Glance Tumor-Specific Antigen Discovery Platform EDGE TM artificial intelligence model for predicting neoantigens and other tumor-specific targets Delivering Neoantigens Personalized GRANITE program & off-the-shelf SLATE program Bispecific Antibodies Cell Therapy (Partnering Only) GRANITE-001 Phase 1 study open and enrolling patients Plan to dose first patient 1Q19 BMS providing CPIs CD8+ T cell responses in NHPs SLATE-001 IND mid-2019 Cash Position of ~$173M* Bispecific antibodies now in lead optimization In-House Manufacturing Capabilities Tumor-specific targets are an opportunity for partnerships bluebird bio collaboration validates EDGE and TCR discovery Strong Foundational IP 4 *Based on 3Q reported cash of $77.4M and net proceeds from IPO of $95.6M

5 Recent Progress at Gritstone since IPO GRANITE - Personalized neoantigen immunotherapy program Phase 1 product candidate successfully manufactured at Gritstone GMP facility - Lot release testing underway for patient #1; expect dosing in 1Q19 as planned Enrollment on track FDA fast-track designation granted in colorectal cancer SLATE - Off-the-shelf, shared neoantigen immunotherapy program Finalizing cassette design first manufacturing runs expected to start in 1Q19 - Multiple novel shared neoantigens validated from human tumors (mutation plus HLA allele) - Most common shared neoantigen expected in >6% of MSS colorectal cancer patients IND filing expected mid-2019 as planned Bispecific antibody (BiSAb) program has entered lead optimization phase Using shared, tumor-specific antigens (including, but not limited to, shared neoantigens) as targets; we are developing novel BiSAb that we believe may open the therapeutic window for solid tumors Superior performance of the EDGE platform (artificial intelligence tumor antigen model) compared to public tools, as published in Nature Biotechnology* *Bulik-Sullivan et al., Nature Biotech.,

6 Gritstone s World-Class Leadership Team, Selected For Expertise in Each Key Domain Andrew Allen, M.D., Ph.D. President & CEO Karin Jooss, Ph.D. CSO Roman Yelensky, Ph.D. CTO Matthew Hawryluk, Ph.D. CBO Raphael Rousseau, M.D., Ph.D. CMO Erin Jones EVP, Regulatory Affairs & Quality Jean-Marc Bellemin CFO Dana B. Johnson VP, Legal Affairs & Compliance 6

7 Tumor Antigens are Central to Cancer Immunotherapy Tumor Cell Peptide HLA Antigens are Targets for Cancer Immunotherapy Targets of the anti-tumor immune response Variable degrees of tumor specificity May enable precise targeting of solid tumors Neoantigens (shared or patient-specific) Drive most pre-existing anti-tumor immune responses Absolutely tumor-specific Limited/no central tolerance Rare: ~1% of all tumor mutations generate a neoantigen Tumor-Specific Antigens (i.e., cancer testis) Commonly shared between patients Can be functionally highly tumor-specific Likely better as cell therapy or BiSAb targets vs. vaccine antigens 7

8 Patients Without Disease Progression or Death (%) Non-Specific Immunotherapy Combinations Drive Modest Efficacy Improvements Phase 3 trial in 945 advanced, untreated, melanoma patients (CheckMate 067) Phase 3 trial in 616 advanced, untreated, non-small cell lung cancer patients (KEYNOTE-189) Hazard ratio for disease progression or death, 0.52 (95% CI, ) P<0.001 Nivolumab + Ipilimumab Nivolumab Ipilimumab Chemotherapy Pembrolizumab + Chemotherapy Adapted from Wolchok et al., NEJM, 2017 Adapted from Gandhi et al., NEJM,

9 T Cell Density (Cells/mm 2 ) Clinical Responses to Checkpoint Inhibitors Mostly Occur in Patients with Pre-Existing Neoantigen-Specific T Cells in Tumors Response in Melanoma Patients Treated with Anti-PD-1 Antibody (Pembrolizumab) is Associated with Anti-Tumor T Cell Infiltration of the Tumor at Baseline Anti-Tumor CD8+ T Cells Most tumor-infiltrating T cells recognize neoantigens Patients without pre-existing CD8+ T cells typically do not respond to checkpoint inhibitor therapy Response Progression Adapted from Tumeh, Ribas et al., Nature, 2014 In patients with progressive disease, Gritstone s immunotherapy seeks to drive a profound T cell response against neoantigen targets 9

10 10 Technologies

11 Potent Platform for T Cell Generation Gritstone s Approach: Next Generation Cancer Immunotherapy Demands Excellence in Two Key Dimensions Target Product Profile T cells Neoantigen Identification 11

12 Model positive predictive value for HLA presented peptides (40% recall) Proprietary EDGE TM Platform: Using Artificial Intelligence to Accurately Identify Mutations That Form True Neoantigens Cancer Cell Public Tools (e.g., NetMHC) EDGE Higher Predictive Value ~9X Improvement over public tool.40 Gritstone EDGE HLA presented mutated peptide (Real neoantigen presented on cell surface) 0 Public Tool Gritstone s EDGE TM Platform Mutation that is not a neoantigen Adapted from Bulik-Sullivan et al., Nature Biotech.,

13 Gritstone EDGE Model Identifies Majority of Real Tumor-Specific Neoantigens Real-World Neoantigen Test Set Results 1 T cell data from patients with responses against tumor specific neoantigens (TSNA) In top 10 predictions: 11 of 12 patients would receive 1 TSNA with EDGE vs. 4 of 12 patients with public methods 2 TIL or PD-1+ PBMC against 26 of >2,000 mutations in 12 patients i.e. 26 TSNA 3 Rank top mutations in each patient as identified via EDGE vs public models 4 Assess how many validated TSNA were selected for vaccine using each approach In top 20: Majority (19/26, 73%) of neoantigens included with EDGE vs. only 9/26 (35%) with public tools Gros, et al., Nature Medicine, 2016; Zacharakis, et al., Nature Medicine, 2018 Tran, et al., Science, 2015; Stronen, et al., Science, 2016 Adapted from Bulik-Sullivan et al., Nature Biotech.,

14 Gritstone has Made Significant Strides in Developing the EDGE Platform TM PATENTED PUBLISHED PARTNERED* Yelensky et al., Neoantigen identification, manufacture and use, US 10,055,540 Bulik-Sullivan et al., Nature Biotech., 2018 *Limited in target number and to use in cell therapy field Gritstone Press Release: bluebird bio and Gritstone Oncology Announce Strategic Collaboration,

15 Developments and Improvements of EDGE Continue TM HLA Class I Increasing HLA coverage across diverse populations Higher positive predictive value (PPV) for HLA peptide presentation Clinical validation of T cell response HLA Class II Up to ~50% of Neoantigen reactive TIL are CD4+* Prediction significantly more challenging than Class I Gritstone generating proprietary dataset for model training Novel Antigen Identification Shared neoantigen discovery for SLATE product candidates Tumor-specific antigen discovery for cell therapy and BiSAb Novel antigen class discovery *Rosenberg, SITC Annual Meeting,

16 Boost Prime Gritstone s Heterologous Prime/Boost Platform Drives Large and Durable T Cell Responses in Non-Human Primates Heterologous Prime/Boost vector switch drives durable, high yield T cell response Alternative Vector Platform Gritstone s Prime/Boost Immunotherapy Platform ChAdV Vector Generates rapid and substantial initial T cell response Vector A Memory Cells Heterologous Prime/Boost Drives profound antigen-specific T cell response samrna** Vector ** Self amplifying RNA 16

17 IFN-g+ T cells/10 6 PBMCs Massive T Cell Responses Across Six Different Antigens in NHP Study; Response Enhanced with Anti-CTLA Gritstone s Immunotherapy Platform ChAdV + samrna + anti-ctla Delivery of boost + anti-ctla Weeks No immune monitoring conducted on week 9 *ELISPOT assay reached saturation in some animals (weeks 13, 21, 33) PBMC: peripheral blood mononuclear cell Gritstone s immunotherapy induces a T cell response that is strong and durable in NHPs 17

18 Immune Response in NHP Comparable to Humans in Adenovirus- Based Prime/Boost HIV Study NHP T cell responses strongly correlated with human T cell responses, including in three key dimensions: 1. Magnitude 2. Kinetics 3. Durability of response APPROACH Trial Ad26 Prime/Ad26 plus high-dose gp140 boost Ad26/Ad26 plus gp140 regimen protected 67% of rhesus monkeys after challenge with heterologous virus Prime: Weeks 0 and 12 Boosts: Weeks 24 and 48 (humans) or 52 (NHPs) Measured T cell response to envelope peptide pools Barouch et al., Lancet,

19 Antigen-Specific T Cells / ml Gritstone s Immunotherapy Regimen Elicits T Cell Responses in NHPs Comparable to Clinically Efficacious T Cell Therapy * * Data derived from: 1. Stevanovic et al., J Clin Onc, Lee et al., Lancet, Robbins et al.,clin Cancer Res,2015 *Estimated from ELISPOT data. Bars represent min and max values 0 ChAdV/samRNA/CPI NHP Study HPV TIL Responders 1 CD19 CAR-T Responders 2 NY-ESO-1 TCR Responders 3 Week 13 ELISPOT In NHPs, Gritstone s immunotherapy induces a T cell response comparable to clinically efficacious treatments 19

20 20 Development Programs

21 Gritstone s Prime/Boost Platform Enables Multiple Product Candidate Options Gritstone s versatile immunotherapy platform enables multiple product candidates for different indications and patient populations using different antigen payloads Prime Boost GRANITE-001 Personalized Neoantigen Immunotherapy Patient specific Driver and passenger mutations Multiple neoantigens delivered Relevant for majority of patients in major tumor types Patient-Specific Neoantigen Payload ChAdV Vector SAM Vector SLATE-001 Off-the-Shelf Neoantigen Immunotherapy Off-the-shelf Driver mutations Efficient patient selection via gene panels Shared Neoantigen Payload 21

22 GRANITE-001: Most Solid Tumor Patients Will Have Their Own Unique Neoantigens Enabling Personalized Immunotherapy Personalized GRANITE Routine Biopsy Sequencing Neoantigen Prediction Personalized Immunotherapy Simple Injection Routine clinical biopsy Routine as input FFPE material clinical biopsy as input material Tumor DNA Tumor exome RNA Normal exome DNA Tumor transcriptome Gritstone EDGE AI model for tumor antigen prediction trained on human tumor data Patient-specific predicted neoantigens inserted into viral and RNA vectors Immunotherapy Immunotherapy administered in conjunction administered with in checkpoint conjunction inhibitors with checkpoint inhibitors Oncologist Gritstone Oncologist 22

23 GRANITE-001 Phase 1 Will Assess Dosing, Safety and Immunogenicity Rapid assessment of immune responses across tumor types in combination with checkpoint blockade Phase 1 Selection Based on Safety Data in Patients with Metastatic Cancer: Lung Gastric Colorectal Bladder All Phase 1 patients receive nivolumab (anti- PD-1) Part A Combine ChAdV (prime) with increasing doses of samrna (boosts) Part B Add subcutaneous (SC) ipilimumab (anti-ctla-4) to prime/boosts ChAdV prime Single Dose + samrna boosts Dose Level 1 samrna boosts Dose Level 2 samrna boosts Dose Level 3 Dose Escalating for Recommended Phase 2 Dose ChAdV prime Single Dose samrna boosts At Recommended Phase 2Dose All part A patients receive full dose ChAdV prime All part B patients receive SC ipilimumab (anti- CTLA-4) 23

24 Clinical Program Focused On Patients with Tumor Neoantigens but with Limited or No Responses to Current Immunotherapy Tumor Mutation Low Burden anti-pd-(l)1 mab NOT a candidate for neoantigen vaccination No neoantigens: Pediatric tumors Tumor Cells de novo T cells Gritstone s Focus GOAL TUMOR TYPE Neoantigen anti-pd-(l)1 mab Neoantigen-specific immunotherapy Generate de novo tumor-specific T Cell responses MSS colorectal cancer existing T cells anti-pd-(l)1 mab Neoantigen-specific immunotherapy de novo T cells existing T cells Generate de novo and amplify existing tumor-specific T Cell responses Non-small cell lung cancer Gastro-esophageal cancer Urothelial cancer High Burden existing T cells anti-pd-(l)1 mab Good response to current Immunotherapies Rx: Melanoma, MSI high tumors 24

25 Proof-of-Concept Is a Therapy-Induced, Objective Tumor Response Driven by New, Tumor-Infiltrating, Neoantigen-Reactive T Cells Gritstone will perform immune monitoring from patient blood and tumor biopsy to determine: Presence of functional neoantigen specific T cells in blood and TCR signature Accumulation and expansion of T cells within tumor tissue and use TCR signature to track neoantigen specific T cells Destruction of tumor cells and shrinkage of tumor (measured by CT scan) 25

26 ctdna May Enable Efficient Clinical Development in Earlier Treatment Settings, e.g. Adjuvant Context Presence of circulating tumor DNA (ctdna) in the adjuvant setting identifies patients who are at high risk of relapse Adjuvant Therapy Context: Favorable Patient Profile: Likely to have better immune responses (vs. advanced disease) Typically have less bulky disease Less genetic heterogeneity Potential Utility of ctdna: Identifies patients at high risk of nearterm recurrence (patient stratification) May have value as a surrogate for efficacy Stage II CRC Gritstone Approach: Drive clinical program into adjuvant setting, leveraging ctdna to enable efficient clinical trials 26 Tie et al., Science Translational Medicine, 2016

27 Treatment Selection Depends Upon Whether the Tumor Displays Personalized or Shared Neoantigens GRANITE -001 SLATE -001 Personalized Immunotherapy Treatment One therapy for one patient Routine Biopsy Shared Immunotherapy Treatment One therapy for many patients EDGE TM 70% - 80% of patient population * 10% - 15% of patient population * * 27 *in certain solid tumors (e.g., NSCLC)

28 SLATE-001 Will Assess Dosing, Safety and Immunogenicity Potential to accelerate execution by leveraging GRANITE-001 dosing and safety data Phase 1 Selected Metastatic Cancer Tumor Types with High Frequency of KRAS Mutation: Lung Pancreatic Colorectal All Phase 1 patients receive anti- PD-1 Part A Combine ChAdV (prime) with increasing doses of samrna (boosts) Part B Add subcutaneous (SC) anti-ctla-4 to prime/boosts ChAdV prime Single Dose + samrna boosts Dose Level 1 samrna boosts Dose Level 2 samrna boosts Dose Level 3 Dose Escalating for Recommended Phase 2 Dose ChAdV prime Single Dose samrna boosts At Recommended Phase 2Dose All part A patients receive full dose ChAdV prime All part B patients receive SC anti- CTLA-4 28

29 Gritstone s Initial Clinical Trial Data Expected in Second Half 2019 GRANITE-001 MSS CRC, NSCLC, muc, GEA GRANITE IND Cleared GRANITE-001 First Patient Enrolled 1Q 2019 GRANITE-001 First Patient Treated 2H 2019 GRANITE-001 Early Data SLATE-001 CRC, NSCLC, PDAC SLATE-001 IND Filing 2H 2019 SLATE-001 First Patient Enrolled 29

30 30 Bispecific Antibody Program

31 Recent ASH Bispecific Antibody Data Offer Early Evidence of Efficacy in Hematologic Malignancies Tumor Response in Relapsed Refractory Lymphoma Patients Treated with CD20xCD3 BiSAb (RG6026) Tumor Response in Relapsed Refractory FL Patients Treated with CD20xCD3 BiSAb (REGN1979) PR SD CR PD Bannerji, ASH Annual Meeting, 2018 Hutchings, ASH Annual Meeting, 2018 Multiple Bispecific Antibodies Drive Complete Remissions in Relapsed Refractory B Cell Lymphomas 31

32 Gritstone Has Identified Antibodies Targeting Shared Antigens that Bind Peptide-HLA Complexes Similarly to TCRs Structural comparison of a TCR-mimetic Ab and a TCR demonstrates that they adopt near-identical binding positions and angles Gritstone s crystal structure of a TCRmimetic Ab binding its HLA-A2/peptide target TCR-mimetic Ab TCR Published crystal structure (Garboczi, et al., Nature, 1996) of a TCR binding its HLA- A2/peptide target peptide TCR-mimetic Ab footprint TCR footprint HLA-A2 footprint schematic (top view) 32

33 Gritstone Developed a Proprietary Bispecific Antibody Platform that Drives Tumor Cell Killing Against EDGE-Identified Target Gritstone BiSAb Platform BiTE Platform Platform A Platform B Platform C Platform D In luciferase assays performed with six different bispecific antibody formats, Gritstone s proprietary BiSAb is potent and drives tumor cell death 33

34 The Gritstone Pipeline Offers Value-Creation and Partnering Opportunities Product Discovery Preclinical Preclinical IND Enabling Phase 1 Partners GRANITE * SLATE Bispecific mab TCRs *Clinical Collaboration 34

35 35 Business Operations

36 Gritstone Has its Own 43,000 sq. ft. Fully Operational Biomanufacturing Facility in California In-house manufacturing capabilities offer control of timelines, cost, quality, and IP Facility Features AT Lab: HPLC purification Multiple clean rooms Process development lab QC release testing lab Analytic technologies lab Controlled materials zone Purification Suite: Concentration and filter of ChAdV Cleanroom Corridor: Buffer bag transport for production 36

37 Key Financial Highlights 3 Months Ended September 30, 2018 Cash, Cash Equivalents and Marketable Securities Research and Development Expenses General and Administrative Expenses $77.4M* $15.6M $3.1M 12 Months Ended December 31, 2017 Cash, Cash Equivalents and Marketable Securities Operating Expenses $86.0M $41.8M 37 *3Q cash position does not include the $95.6M in net proceeds from IPO

38 Multiple Value-Generating Milestones Over Next 6-18 Months Partnership for Shared Tumor Antigens Anticipated Milestones 2H18 1H19 2H19 GRANITE IND Cleared GRANITE-001 Phase 1 Initiation SLATE-001 IND Filing SLATE-001 Clinical Study Initiation GRANITE-001 Early Data Bispecific mab Development Candidate Nomination 38

39 Personalized Cancer Immunotherapy May Offer the Next Wave of Immunotherapy Breakthroughs, Driving Tumor Specific Immune Attack Characterize tumor antigen landscape for each patient Select optimal T cell therapeutic approach Combine with immune enhancers Lineage Marker (e.g. CD19) Shared Tumor-Specific Antigen (e.g. MAGE-A1) Neoantigen Immunotherapy Anti-PD-(L)1 mab Anti-CTLA-4 mab Bispecific mab A2R Inhibitor CAR-T/Engineered TCR Other Tumor- Associated Antigen (e.g. HER-2) Tumor-Specific Neoantigen 39

40 40 Thank You!