Determined to realize a future in which people with cancer live longer and better than ever before CORPORATE PRESENTATION JULY 2018 1
Forward-looking statements disclosure This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate" and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding future operations, financial results and the financial condition of Syndax Pharmaceuticals, Inc. ( Syndax or the Company ), including financial position, strategy and plans, the progress, timing, clinical development and scope of clinical trials and the reporting of clinical data for Syndax s product candidates, and Syndax s expectations for liquidity and future operations, are forward-looking statements. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, clinical site activation rates or clinical trial enrollment rates that are lower than expected, changes in expected or existing competition, failure of our collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes. Moreover, Syndax operates in a very competitive and rapidly changing environment. Other factors that may cause our actual results to differ from current expectations are discussed in Syndax s filings with the U.S. Securities and Exchange Commission, including the Risk Factors sections contained therein. New risks emerge from time to time. It is not possible for Syndax s management to predict all risks, nor can Syndax assess the impact of all factors on its business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statement. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied. Except as required by law, neither Syndax nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements. Syndax undertakes no obligation to update publicly any forward-looking statements for any reason after the date of this presentation to conform these statements to actual results or to changes in Syndax s expectations. 2
Company strategy Entinostat SNDX-6352 anti-csf1r Ab Menin-MLLr inhibitors New molecules Breast Cancer Immunooncology Immuno-oncology Financing & Staffing 3
Syndax investment highlights Entinostat Combo with exemestane: Phase 3 PFS data 3Q18 $$B US opportunity Combo with anti-pd-(l)1: Positive data in Mel, NSCLC Ongoing NSCLC, Mel, CRC, TNBC, Ovar trials Multiple data readouts $$$$B US opportunity SNDX-6352 CSF1R antibody: Phase 1 multiple dose study ongoing Broad clinical dev potential Collaboration with AZ s IMFINZI Menin-MLLr inh Onc driver specific: MLLr leukemias IND in 2019 CRC colorectal cancer; NSCLC non-small cell lung cancer; Mel melanoma; TNBC triple negative breast cancer; Ovar ovarian cancer 4
Upcoming milestones ENTINOSTAT (Class 1 specific HDAC inhibitor) 2Q18 3Q18 4Q18 1H19 E2112 - Complete Phase 3 enrollment; release PFS ENCORE 601 Final data for PD-(L)1 pretx NSCLC, MEL cohorts ENCORE 601 Registration trial decision for melanoma ENCORE 601 Go / No go decision, Stage 1 of MSS CRC cohort ENCORE 602 Report topline TNBC results ENCORE 603 Report topline Ovarian results SNDX-6352 (anti-csf-1r mab) 2Q18 3Q18 4Q18 1H19 MAD trial data presentation (cancer patients) Menin MLLr inhibitor 2Q18 3Q18 4Q18 1H19 File IND and initiate clinical studies 5
Entinostat re-sensitizes cancer cells ERα+ Breast Cancer Acquires Hormone Resistance estrogen acquired resistance to hormone therapy estrogen estrogen drives tumor growth sensitive to hormone therapy + entinostat drive tumor growth to hormone therapy ERα+ breast cancer cell ERα+ breast cancer cell 6
Phase 2 trial resulted in breakthrough therapy designation Progression-free Survival Overall Survival Progression probability 1.00 0.75 0.50 0.25 EE: median PFS 4.3 months EP: median PFS 2.3 months Hazard ratio 0.73 (95% CI: 0.50, 1.07) P=0.055 (1-sided) EE = exemestane plus entinostat EP = exemestane plus placebo Survival probability 1.00 0.75 0.50 0.25 EE: median OS 28.1 months EP: median OS 19.8 months Hazard Ratio 0.59 (95% CI: 0.36, 0.97) P=0.036 (2-sided) ; P=0.018 (1-sided) 0.00 0 2 4 6 8 10 12 14 16 18 20 22 24 26 Months Placebo 31/66 13/33 4/20 5/16 2/11 4/9 0/5 1/4 1/3 1/1 0/0 0/0 0/0 Entinostat 15/64 14/45 11/29 3/174/14 2/10 0/8 0/8 3/8 2/5 0/1 0/1 0/1 (#events / #at risk) 0.00 0 6 12 18 24 30 36 42 Months Placebo 4/66 13/60 12/47 8/35 5/18 1/3 0/0 Entinostat 4/64 5/55 4/49 9/43 3/21 2/9 0/1 (#events / #at risk) Yardley, Denise A., et al. Journal of Clinical Oncology 31.17 (2013): 2128-2135 7
Phase 3 E2112 PFS data anticipated 3Q18 E2112: Exemestane +/- entinostat Advanced HR+ HER2- BC following SOC progression (Accrual goal: n=600) Exemestane + entinostat (n=300) Randomized, blinded Exemestane + placebo (n=300) Two primary endpoints: PFS and OS E2112 Trial Milestones 4Q17: Final PFS analysis, 1 st interim OS analysis complete 2Q18: 2 nd interim OS analysis complete 3Q18: Expect to Achieve full accrual, share result of PFS analysis 2H18: If PFS positive, File NDA 2018-20: Early trial completion possible w/may & Nov interim OS analyses 2018 2019 2020 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 8
Blockbuster potential as 2 nd /3 rd line First novel MOA in HR+ BC with Phase 3 data since CDK4/6 Leading treatment options HR+, HER2- advanced breast cancer 1 st line hormone Tx 2 nd /3 rd /4 th line hormone Tx Chemo-Tx Anastrozole or letrazole +/- CDK4,6 inhibitor Anastrazole, Faslodex +/- CDK4,6 inhibitor or Afinitorexemestane 34,000 pts Entinostat-exemestane target population Capecitabine, gemcitabine, eribulin Source: DataMonitor 2016 Breast cancer: HR+/HER2- Disease Coverage Report 9
ENCORE Clinical Trial Program: Evaluating entinostat s potential to enhance anti-pd-(l)1 efficacy TNBC HR+ BC MEL NSCLC CRC OVAR PD-(L)1 Immune cells Tumor mutational burden (TMB) Nanostring Focused on early signs of efficacy and biomarkers that predict clinical benefit 10
ENCORE 601 / KEYNOTE 142 study design Entinostat + KEYTRUDA Phase 1b: Open-label Completed Dose & safety confirmation / biomarker assessment Phase 2: Open-label Ongoing NSCLC PD-1/PD-(L)1 naïve NSCLC Progressed on PD-1/PD-(L)1 Melanoma Progressed on PD-1 Primary endpoint irrecist ORR MSS CRC PD-1/PD-(L)1 naïve MSS CRC - Microsatellite stable colorectal cancer, irrecist immune related response evaluation criteria solid tumors 11
PD-1 relapsed/refractory NSCLC cohort ENCORE 601: PD-1 pre-tx NSCLC 76 pts enrolled, first 57 presented at ASCO 6 confirmed responses in total pop (11% ORR; 95% CI:4-21%) 28.6% ORR in significant subset. Median duration of response 4.6 months Acceptable safety profile Further update expected 3Q18 12
ENCORE 601 PD-1 relapsed/refractory NSCLC Primary Endpoint: Overall Response Rate = 11% [95% CI (4% - 21%)] 50% 35% Change from baseline (%) 5% -25% -55% -85% Partial response (confirmed) Partial response (unconfirmed) Stable disease Progressive disease Source: Gandhi, L et al ASCO Annual Meeting 2018 13
Differentiated mechanism targets tumor microenvironment (TME) T REG Immune suppressor cells MDSC Entinostat inhibits Myeloid derived suppressor cells (MDSCs) and T-Regulatory cells (Tregs) in the TME Tumor microenvironment CTLA-4 Cytotoxic T-cell PD-1 Entinostat s activity synergizes with PD-(L)1 to activate immune system against cancer checkpoint inhibitors Tumor Cell Tumor surface Hypothesis: Entinostat can reverse resistance to PD-1 antagonists
Monocytes identify patients likely to benefit However, before commencing therapy, a strong predictor of progression-free and overall survival in response to anti-pd-1 immunotherapy was the frequency of CD14+CD16 HLA-DRhi monocytes we propose that the frequency of monocytes in PBMCs may serve in clinical decision support. Source: Kreig, C. et al Nature Med; 24(2) 2018 144-154 15
Higher baseline associated with clinical benefit Objective Response Objective Response and/or Total time on therapy >24 wks 30 N=6 N=45 30 N=10 N=41 % of live PBMCs 20 10 N=15 % of live PBMCs 20 10 N=15 0 0 Source: Gandhi, L et al ASCO Annual Meeting 2018 16
Higher baseline associated with PFS, ORR benefit Monocyte high subset may be ~30% of PD-1 relapsed / refractory NSCLC Source: Gandhi, L et al ASCO Annual Meeting 2018 17
High monocytes correspond to inflamed TME Gene expression in baseline tumor biopsies from a subset of patients (n = 18) associated with peripheral blood monocyte levels Tumor inflammation signature Monocyte-high subset of patients display increased inflamed gene expression signature relative to monocyte-low. Data suggests entinostat is restoring anti-tumor activity of Keytruda in inflamed cancers n = 14 n = 4 TIS - Tumor inflammation signature score assessed with Nanostring PanCancer IO 360TM panel. 18 genes: CCL5, CD8A, STAT1, PDL2, HLA-DQA1, HLA-DRB1,CXCL9, CXCR6, TIGIT, PDL1, HLA-E, CMKLR1, CD27, IDO1, LAG3, CD276, PSMB10, NKG7 Source: Gandhi, L et al ASCO Annual Meeting 2018 18
Patient segmentation common in NSCLC therapy NSCLC Patient Journey by Line of Therapy (US) Biomarkers used to identify responders (EGFR, ALK, PD-(L)1, TMB) Selection may enable entinostat-keytruda to provide meaningful benefit for a subset of 2L / 3L NSCLC Pembro + platinum + pemetrexed 1 st line 2 nd / 3 rd line PDL-1 High PD-(L)1 monotx Platinum doublet PDL-1 Low ~135,000 pts Chemo ~84,000 pts PD-(L)1 monotx ~33% qualify for combo Pembro-entinostat ~30,000 pts Source: Kantar 2016 Treatment Architecture report; Trial Trove, SEER data = in development 19
Potential registration path in NSCLC Entinostat s MOA targets immunosuppressive effects in the tumor microenvironment ENCORE 601 provides evidence that entinostat KEYTRUDA combination may benefit patients relapsed or refractory to anti-pd-1 High circulating levels of classical monocytes correspond to an inflamed tumor microenvironment and are associated with an enhanced response to the entinostat KEYTRUDA combination Syndax will continue to monitor results from the ENCORE 601 cohort and initiate a trial(s) to confirm and extend these observations. 20
Alternative treatment options needed for melanoma Metastatic melanoma patient journey 1 st L CTLA-4/PD-1 combo PD-1 MonoTx PD-1 MonoTx 2 nd L CTLA-4 MonoTx ORR 11-14% carboplatin, dacarbazine, temozolomide or paclitaxel ORR 4-11% 21
PD-1 relapsed/refractory melanoma cohort ENCORE 601: PD-1 pre-tx Melanoma 55 pts enrolled, first 34 presented at ASCO 6 confirmed responses in total population (18% ORR; 95% CI:7-35%) 65% refractory to CTLA-4 and PD-1 18% ORR in this population Median duration of response 9 months Acceptable safety profile Monocyte analysis ongoing Target population: 10,000 15,000 Registration trial decision 4Q18 22
Combination may improve anti-tumor effect Pre-clinical evidence that entinostat-nktr-214 combo enhances immune activation and anti-tumor activity presented at AACR 1 Syndax and Nektar collaborate to explore efficacy in patients with melanoma who have previously progressed on anti- PD-1 therapy Source: 1. Wang L et al AACR Annual Meeting 2018 23
May increase anti-tumor effect by modulating immunosuppressive cells Phase 2 Entinostat HD IL-2 RCC 1 data support hypothesis Enrolled 43 metastatic ccrcc pts oral entinostat, q2wk HD IL-2 dosed q8hr (days 1-5,15-19 of 85 day cycle) ORR = 37% (15/41) 95% CI (22-53%) 3 CR (7%); 12 PR (29%) Median PFS = 13.8 mo Median OS = 65.3 mo Progression free survival Progression-Free Survival Proleukin entinostat mpfs 13.8 mo Time at risk (mo) Proleukin Historic mpfs ~ 4 months Source: 1.Pili R et al Clin Cancer Res; 23(23) 2017 7199-7208 24
Unmet need for CTLA-4 and PD-1 treated patients Metastatic melanoma patient journey 1 st L CTLA4/PD-1 combo PD-1 MonoTx PD-1 MonoTx 2 nd L CTLA4 MonoTx ORR 11-14% Entinostat - KEYTRUDA Entinostat NKTR-214 carboplatin, dacarbazine, temozolomide or paclitaxel ORR 4-11% 25
Microsatellite stable colorectal cancer cohort ENCORE 601: PD-1 Naïve MSS-CRC Available data from first 16 patients 1 confirmed response (6% ORR; 95% CI: 0-32) Median PFS of 12.3 weeks Duration of response > 7 months Acceptable safety profile Target population: ~17,000 Enrolling 21 additional patients, data 1H19 26
ENCORE 602, 603: Data available 1H19 ENCORE 602: TNBC ENCORE 603: Ovarian TECENTRIQ - entinostat dose determination Phase 1b: Open-label BAVENCIO - entinostat dose determination TECENTRIQ + entinostat (n=35) TECENTRIQ + placebo (n=35) Phase 2: Randomized, double-blind BAVENCIO + entinostat (n=80) BAVENCIO + placebo (n=40) Complete enrollment 2Q18 Enrollment completed 2Q18 Phase 2 ENDPOINTS: Primary endpoint - PFS Secondary endpoint - Overall response rate (ORR) Secondary endpoint - Overall survival (OS) 27
ENCORE Clinical Trial Program: Evaluating entinostat s potential to enhance anti-pd-(l)1 efficacy PD-(L)1 Immune cells Tumor mutational burden (TMB) Nanostring TNBC HR+ BC NSCLC MEL CRC OVAR Awaiting final Progress Await data Await data Await data phase 2 results
SNDX-6352: Anticipate focused Phase 2 POC program High affinity, IgG4 (K D = 4-8 pm) Multiple ascending dose (MAD, solid tumors) ongoing CSF-1 Receptor Ligand binding Dimerisation SNDX-6352 Collaboration in place to broadly study combination with IMFINZI (AZ) Commence work to establish safety of combination in 2Q18 Communicate Phase 2 strategy 2H18 ATP binding Kinase insert Kinase domain P P P P P TAM tumor associated macrophage; CSF-1R colony stimulating factor -1 receptor Source : Ordentlich, P. et al SITC 2016 29
Menin-MLLr program on track for IND Filing 1H19 MLL-r known cause of leukemias (AML, ALL, MLL) Major market incidence: 4,000/yr NPM1 mut also targeted by MLLr inhibitor Estimated at 25-30% of adult AML Other potential indications: MDS, ALL, AML (incl. MLL-PTD AML) CMML and CML Pancreatic Cancer Gain-of-function p53 mutation tumors VTP-50469 data presented at AACR MLLr Inhibitor MLL-r = rearrangements of the Mixed Lineage Leukemia (MLL) gene 30
Proven ability to build the pipeline Established relationships enhance identification and access to quality assets Clinical development leadership enables competitive advantage 3Q16: UCB SNDX-6352 4Q17: Allergan/Vitae Business development continues to be a core strength of our business Menin-MLLr inhibitors 31
1Q18 financial highlights and 2018 guidance Ticker Cash and short-term investments Common shares O/S SNDX (NASDAQ) As of March 31, 2018 $113.2 million 24.7 million 2018 Operating Expense Guidance Q2 2018 R&D Total Operating Expenses $15-17 M $60-64 M $20-22 M $78-84 M 32
Upcoming milestones ENTINOSTAT (Class 1 specific HDAC inhibitor) 2Q18 3Q18 4Q18 1H19 E2112 - Complete Phase 3 enrollment; release PFS ENCORE 601 Final data for PD-(L)1 pretx NSCLC, MEL cohorts ENCORE 601 Registration trial decision for melanoma ENCORE 601 Go / No go decision, Stage 1 of MSS CRC cohort ENCORE 602 Report topline TNBC results ENCORE 603 Report topline Ovarian results SNDX-6352 (anti-csf-1r mab) 2Q18 3Q18 4Q18 1H19 MAD trial data presentation (cancer patients) Menin MLLr inhibitor 2Q18 3Q18 4Q18 1H19 File IND and initiate clinical studies 33
Syndax investment highlights Entinostat Combo with exemestane: Phase 3 PFS data 3Q18 $$B US opportunity Combo with anti-pd-(l)1: Positive data in Mel, NSCLC Ongoing NSCLC, Mel, CRC, TNBC, Ovar trials Multiple data readouts $$$$B US opportunity SNDX-6352 CSF1R antibody: Phase 1 multiple dose study ongoing Broad clinical dev potential Collaboration with AZ s IMFINZI Menin-MLLr inh Onc driver specific: MLLr leukemias IND in 2019 CRC colorectal cancer; NSCLC non-small cell lung cancer; Mel melanoma; TNBC triple negative breast cancer; Ovar ovarian cancer 34
Thank you. Questions? 35