Jounce Therapeutics A Next Gen Immunotherapy Company
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Investment Highlights and Differentiation Advancing our Diverse Pipeline Robust Translational Science Platform • Three immunotherapies in the clinic in 2019 • Commitment to translational approach – JTX-2011 (ICOS) Phase 1/2 – New programs linked to immune cell composition – JTX-4014 (PD-1) Phase 1 in tumors – JTX-8064 (LILRB2) progress to IND / Phase 1 – Analysis of responding versus non-responding patients to inform mechanism and biomarkers • Advancing additional novel discovery programs Financial & Strategic Strength Experienced Founders & Management Team • Strong balance sheet • Founders with fundamental roles in IO biology: • Strategic collaboration with co-development Coley, Lasker and Nobel awards and co-commercialization features • Management with broad R&D and commercial experience including leadership roles in 3 | Jounce Therapeutics © January 2019
DELIVERING VALUE PIPELINE EXECUTION APPROACH & IO OPPORTUNITY 4 | Jounce Therapeutics © January 2019
The Jounce Solution: Next Generation IO Will Require a Translational Approach Next Generation IO: Translational Science Innovative Pipeline What Will it Take? Platform • Identify the right patients • Biomarker driven approach Tumor Immune Infiltrate • Move beyond PD-1 centric • Rational, science-based approach Gene Signatures combinations • Address unmet need in Blood Cell Population • Diverse pipeline targeting tumors without T cells multiple immune cells Mutational Analysis Bioinformatics 5 | Jounce Therapeutics © January 2019
Jounce Immunotherapy Pipeline Development Programs Clinical Program Target Biology Preclinical Phase 1 Phase 2 Phase 3 CD4 T cell JTX-2011 ICOS focused CD8 T cell JTX-4014 PD-1 focused Suppressive JTX-8064 LILRB2 macrophage, colder tumor Research Programs Named Celgene Option Celgene Target Pool Target Rights Stromal Jounce Wholly-owned Macrophage, B-cell, T-reg Celgene Target Pool Reverse translational work leading to new targets, methods and paradigms 6 | Jounce Therapeutics © January 2019
Development Programs JTX-2011 JTX-8064 JTX-4014
JTX-2011 Mechanism: ICOS Agonist Clinical Evidence of Peripheral Agonism Activation of T effector cells APC APC IFN-Y IFN-Y st 1st signalICOS JTX-2011 TCR IFN-Y TCR IFN-Y TCR ICOS ↑ ICOS ICOS ↑IFN-γ “Non-Primed” “Primed” T effector cell T effector cell NK cell Selective reduction of T regulatory cell intratumoral T regulatory cells 8 | Jounce Therapeutics © January 2019
JTX-2011: Key Learnings from Phase 1/2 ICONIC Trial Safety • JTX-2011 safe and well tolerated alone and in combination with nivolumab Preliminary Efficacy* • All durable responses and tumor reductions associated with ICOS PD biomarker – RECIST PRs in PD-1i naïve patients – Tumor reductions in PD-1i failures – All responses durable (PR ≥ 6 months) – All responders reported at ASCO 2018 on study for >1 year Patient Characteristics • Heavily pre-treated patients; high early discontinuation rate • Late lines of therapy more challenging to treat with IO therapy • Multiple solid tumors including NSCLC, HNSCC, Gastric, TNBC *Based on investigator assessments; PD-1i = PD-1 inhibitor or PD-L1 inhibitor 9 | Jounce Therapeutics © January 2019
JTX-2011: Anti-Tumor Activity Correlates with Mechanistic Biomarker ICOS hi CD4 Cells Emerge in Patients with Target Lesion Reductions* • Observed in 7/7 subjects with target lesion PR • Not observed in 12/12 subjects with target lesion progression Limited longitudinal samples for some subjects N= 45 subjects from mono and combo cohorts with evaluable samples Data cut-off as of December 18, 2018 >30% target lesion reduction *Best response observed for target lesion, based on investigator assessments 10 | Jounce Therapeutics © January 2019
The Importance of ICOS hi CD4 Cells PD-1i Does Not Induce ICOS hi CD4 Cells JTX-2011 Amplifies an Immune Response Emergence of ICOS hi CD4 cells is due to JTX-2011 Only ICOS hi CD4 cells can be activated by JTX-2011 • 77 patients treated with PD-1i monotherapy 5 0 0 0 5 0 0 0 I N F y I N F y T N F a T N F a 4 0 0 0 I L - 2 • 6 confirmed responders 4 0 0 0 I L - 2 I I F F M M 3 0 0 0 • 0 patients with ICOS hi CD4 cells 3 0 0 0 n a n e a e M o M 2 0 0 0 e o 2 0 0 0 e G G 1 0 0 0 1 0 0 0 0 0 C o n t r o l S o l u b l e J T X - 2 0 1 1 Harvey, Jounce Therapeutics as of SITC 2018 C o n t r o l S o l u b l e J T X - 2 0 1 1 1 5 0 0 0 I N F y 1 5 0 0 0 11 | Jounce Therapeutics © January 2019 T N F a I L - 2 I F 1 0 0 0 0 I N F y M I n F 1 0 0 0 0 T N F a a M e I L - 2 n M a o e e M G 5 0 0 0 o e G 5 0 0 0 0 C o n t r o l S o l u b l e J T X - 2 0 1 1 0 C o n t r o l S o l u b l e J T X - 2 0 1 1 8 0 0 0 8 0 0 0 I N F y T N F a 6 0 0 0 I L - 2 I F M 6 0 0 0 n I N F y a I e F T N F a 4 0 0 0 M M I L - 2 o n e a G e 4 0 0 0 M 2 0 0 0 o e G 2 0 0 0 0 C o n t r o l S o l u b l e J T X - 2 0 1 1 0 C o n t r o l S o l u b l e J T X - 2 0 1 1
JTX-2011: Reverse Translational Work Leads to Two Development Paths Predictive Biomarker CTLA-4i Combination Two Prioritize combination Development Identify baseline agents that induce Paths characteristics to predict which patients are able to ICOS hi CD4 cells induce ICOS hi CD4 cells Induction of ICOS by Ipilimumab Limited longitudinal samples for some subjects >30% target Carthon et al, Clin Can Res (2010) Data cut-off as of December 18, 2018 lesion reduction Move beyond PD-1 centric approach Identify the right patients 12 | Jounce Therapeutics © January 2019
JTX-2011 Development Paths: New Phase 2 Studies New Phase 2 JTX-2011 Upcoming Preliminary Efficacy Milestones New Schedules & Combination Sequences CTLA-4i • Initiate new Phase 2 studies PD-1i Experienced NSCLC • ICONIC data update – PFS and OS PD-1i Experienced Bladder – Further mechanistic and predictive biomarker PD-1i Naïve Bladder reverse translational data • Preliminary efficacy data PD-1i and/or monotherapy expected in 2020 • Predictive Biomarker • Multiple Tumor Types 13 | Jounce Therapeutics © January 2019
JTX-2011: Opportunity in PD-1i Experienced NSCLC Patients with Driver Mutation Negative Stage IV NSCLC Rationale • Re-treatment of PD-1i failures with PD-1i 1L Platinum chemo PD-1i +/- chemo combinations has not addressed the unmet need • Tumor reductions observed in ICONIC PD-1i failure NSCLC patients*, 2L PD-1i Docetaxel ORR ~6% accompanied by ICOS hi cells PD-1i failure patients; • CTLA-4i combination activity in NSCLC High unmet need Docetaxel • Large market opportunity with the potential 3L ORR ~6% Sequenced combination for a fast path to approval CTLA-4i & JTX-2011 *As presented at ASCO 2018 Source: Docetaxel prescribing info (Sanofi-Aventis and generic labels), ASCO guidelines, Decision Resources Group: NSCLC Disease Landscape & Forecast 2018, NCCN Guidelines®, primary market research 14 | Jounce Therapeutics © January 2019
JTX-2011: Opportunities in PD-1i Experienced and Naïve Bladder Patients Patients with Stage IV Bladder Cancer Rationale • PD-1i experienced: similar market 1L Cisplatin + gemcitabine Single-agent PD-1i or chemo (cisplatin-eligible) (cis/platinum ineligible) drivers as in NSCLC Unmet need in IO naïve patients CTLA-4i and JTX- • PD-1i naïve: relatively low PD-1i Single-agent PD-1i 2011 response rates in chemo-ineligible 2L and chemo failure patients Single-agent chemo PD-1i naïve PD-1i experienced Unmet need in • CTLA-4i shown to induce ICOS hi PD-1i failures CTLA-4i and JTX- CD4 cells in bladder cancer* 2011 3L Single-agent chemo * Carthon et al, Clin Can Res (2010) Source: ASCO guidelines, Decision Resources Group: Bladder Cancer Disease Landscape & Forecast 2018, NCCN Guidelines®, primary market research 15 | Jounce Therapeutics © January 2019
Development Programs JTX-2011 JTX-8064 JTX-4014
Discovery Platform Relies on Human Immune Tumor Composition HOT T cells in the tumor COLD Macrophages in the tumor Potential single agent PD-1i Highest responders Unmet need 17 | Jounce Therapeutics © January 2019
JTX-8064: LILRB2* Inhibitor Highly Selective Monoclonal Antibody Reprograms Human Macrophages to Anti-Tumor Phenotype Pro-Inflammatory Anti-Inflammatory • TNFa • CCL2 • IL-6 • IL-10 JTX-8064 promotes M1-like activation JTX-8064 attenuates M2-like activation 1 0 0 0 0 1 0 0 0 0 8 0 0 0 d 8 0 0 0 d e e c Control mAb c JTX-8064 ) ) u u L L 6 0 0 0 6 0 0 0 d d o m m o r / / r p g g p p p 4 0 0 0 4 0 0 0 0 ( ( 6 1 - JTX-8064 - L I L 2 0 0 0 I 2 0 0 0 Control mAb 0 0 0 . 0 0 0 0 0 1 0 . 0 0 0 1 0 . 0 1 1 1 0 0 0 . 0 0 0 0 0 1 0 . 0 0 0 1 0 . 0 1 1 1 0 0 A n t i b o d y C o n c e n t r a t i o n ( g / m L ) A n t i b o d y C o n c e n t r a t i o n ( g / m L ) * Also known as ILT4 18 | Jounce Therapeutics © January 2019
Deletion of PirB (LILRB2 Analog) Results in Anti-Tumor Activity Mouse expressing normal PirB target Mouse lacking PirB target MC38 tumor (macrophage staining) W T M C 3 8 P ir B M C 3 8 3 5 0 0 3 5 0 0 ) ) 3 3 3 0 0 0 3 0 0 0 m m m m 2 5 0 0 ( 2 5 0 0 ( e e m 2 0 0 0 2 0 0 0 m u u l l o 1 5 0 0 o 1 5 0 0 V V r r o 1 0 0 0 1 0 0 0 o m m u 5 0 0 u 5 0 0 T T 0 0 0 1 0 2 0 3 0 0 1 0 2 0 3 0 D a y D a y IND filing and initiation of Phase 1 expected in 2019 19 | Jounce Therapeutics © January 2019
Development Programs JTX-2011 JTX-8064 JTX-4014
JTX-4014: PD-1i Program On Track • IND filed Sept 2018 • Enrollment in first cohort completed • Establish safety and RP2D in 2019 Well-characterized PD-1 antibody Objective: Monotherapy safety & POC • Fully human IgG4 • For use in combinations with potential • Blocks binding to PD-L1 and PD-L2 future product candidates 21 | Jounce Therapeutics © January 2019
DELIVERING VALUE PIPELINE EXECUTION APPROACH & IO OPPORTUNITY 22 | Jounce Therapeutics © January 2019
2018 Accomplishments and 2019 Upcoming Milestones 2018 2019 ✓ Reported JTX-2011 preliminary clinical ▪ Three immunotherapies in the clinic efficacy results in Q2 ▪ JTX-2011: Data update including PFS ✓ Initiated new JTX-2011 combination and OS from ICONIC in 1H (CTLA-4i) ▪ JTX-2011: Initiate new Phase 2 studies ✓ Advanced next development ▪ JTX-4014: Establish safety and RP2D candidate into IND enabling activities ▪ JTX-8064: File IND and initiate Phase 1 ✓ Submitted IND for JTX-4014 ▪ (PD-1i) Advance next development candidate into IND enabling studies 23 | Jounce Therapeutics © January 2019
Financial Strength and Flexibility Company History • Strong balance sheet: – ~$215M cash and investments, Event Date Gross $ Comment as of September 30, 2018 Series A 2013 $47M Third Rock • Financial guidance: Ventures – End 2018 with $185M - $195M in cash Series B 2015 $56M Fidelity, – 2019 cash burn $80M - $95M Wellington, others – 2019 revenue of $50M - $60M (non-cash) CELG 2016 $225M US profit sharing Collaboration upfront on optioned • Common stock outstanding: $36M programs – 32.7M shares as of November 9, 2018 equity Initial Public 2017 $117M Upsized deal Offering (gross) 24 | Jounce Therapeutics © January 2019
Jounce Therapeutics A Next Gen Immunotherapy Company
