Syndax Pharmaceuticals, Inc. · NASDAQ:SNDX
Syndax Pharmaceuticals — Technical Presentation (March 2019)
16 slides from Syndax Pharmaceuticals's technical presentation, March 2019
Slide 1: Identification of Gene Signatures Associated With Response in a Phase 2 Trial of Entinostat
Identification of Gene Signatures Associated With Response in a Phase 2 Trial of Entinostat (ENT) Plus Pembrolizumab (PEMBRO) in Non-Small Cell Lung Cancer (NSCLC) Patients Whose Disease Has Progressed on or After Anti-PD-(L)1 Therapy Suresh Ramalingam1, Peter Ordentlich2, Lei Wang2, David Tamang2,
Slide 2: Disclosures
Disclosures Dr. Ramalingam has served on scientific advisory board meetings for AbbVie, Amgen, Astra Zeneca, Bristol-Myers Squibb, Genentech/Roche, Loxo, Merck, Nektar, and Takeda Dr. Ramalingam has received research support (to institution) from Advaxis, Amgen, Astra Zeneca, Bristol-Myers Squibb, M
Slide 3: Immune Checkpoint Inhibition in NSCLC
Immune Checkpoint Inhibition in NSCLC PD-1/PD-L1 inhibitors are approved for patients with metastatic NSCLC • First-line therapy (monotherapy) • First-line therapy (combination with chemotherapy) • Second-line therapy (monotherapy) There is an unmet need for novel options for patients who have disea
Slide 4: Proposed Mechanism(s) of Action of Entinostat to Enhance IO Approaches
Proposed Mechanism(s) of Action of Entinostat to Enhance IO Approaches • Entinostat (ENT) is an oral class I- selective histone deacetylase inhibitor • ENT reduces MDSC and Treg number & function • ENT induces pro-inflammatory cascade in TME • ENT enhances antigen presentation • Additional beneficia
Slide 5: ENCORE-601 / KEYNOTE 142 Study Overview
ENCORE-601 / KEYNOTE 142 Study Overview Phase 2 open label study assessing ENT 5 mg PO QW + PEMBRO 200 mg IV Q3W in patients with NSCLC who had progressed on/after anti-PD-1/PD-L1 therapy Inclusion Criteria • Recurrent or metastatic NSCLC, measurable by RECIST 1.1 • Prior progression on/after anti-P
Slide 6: Patient Baseline Demographics and PD-(L)1 History
Patient Baseline Demographics and PD-(L)1 History Demographics N=72 PD-(L)1 history N=72 Male, n (%) 38 (53%) Best response on prior anti-PD-(L)1, n (%) Median age (range) 66 yrs (30-85) Complete Response 1 (1%) ECOG PS, n (%) Partial Response 5 (7%) 0 / 1 / Missing 19 (26%) / 52 (72%) / 1 (1%) Stab
Slide 7: Durable Responses Were Observed in Patients Who Experienced Progression on Prior Anti-PD(L)1 Therapy
Durable Responses Were Observed in Patients Who Experienced Progression on Prior Anti-PD(L)1 Therapy • Overall Response Rate* = 10% (95% CI: 4% - 19%) ‒ 50% SD 100 • Median duration of response = 8 months (range 3-18) 75 • Median PFS 2.8 months (95% CI: 2.1 – 4.1) % Change Relative to Baseline 50 20
Slide 8: Tissue/Blood Sampling Overview
Tissue/Blood Sampling Overview Cycle 1, Day 1 Cycle 2, Day 1 Cycle 2, Day 15 Tumor Biopsy X Blood Sample X X X • Cycle 1, Day 1 (pretreatment) monocyte data available for 65/72 (90%) of patients • Cycle 1, Day 1 (pretreatment) gene expression available for 43/72 (60%) of patients Cycle = 3 weeks 8
Slide 9: Biomarkers: Identifying Factors That May Predict Response to ENT + PEMBRO
Biomarkers: Identifying Factors That May Predict Response to ENT + PEMBRO • No significant association of response with High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy ‒ Smoking status Nonresponder Responder ‒ PD-L1 expression 40 ‒ Prior PD-(L)1 treatment history C
Slide 10: Baseline Peripheral Classical Monocytes May Predict Clinical Benefit in NSCLC Cohort
Baseline Peripheral Classical Monocytes May Predict Clinical Benefit in NSCLC Cohort 100 mPFS (95% CI) MonocyteHigh 4.7 months (2.7-11.1) 80 4.7 MonocyteLow 2.7 months (1.4-3.0) mos 60 Patients with high PFS (%) 50 levels of monocyte at baseline 40 experienced a significantly longer 20 2.7 PFS benef
Slide 11: Majority of Responders Had High Monocytes at Baseline
Majority of Responders Had High Monocytes at Baseline Pretreatment classical monocytes (NSCLC) 40 HLA-DRhi Classical Monocyte (%) Responders with 30 high baseline monocytes also 20 experienced enhanced durability 10 Monocyte High 0 Monocyte Low Responders Nonresponders Healthy donors Confirmed PR (n
Slide 12: Evaluation of Baseline Tumor Tissue
Evaluation of Baseline Tumor Tissue • Gene expression analyses of pre-treatment tumor biopsies to identify signatures associated with response • RNAseq / Nanostring available for ~60% of patients • Geneset enrichment analysis identifying pathways of interest including signaling pathways tied to enti
Slide 13: MYC Signaling Enriched in Responders
MYC Signaling Enriched in Responders Enrichment of MYC Hallmark genesets in pre-treatment tumors from anti-PD-1 pretreated NSCLC patients responding to pembrolizumab plus entinostat 13
Slide 14: Gene Expression Analysis on Tumor Biopsies Identified High Baseline MYC Activity in ENCORE-601 Responders
Gene Expression Analysis on Tumor Biopsies Identified High Baseline MYC Activity in ENCORE-601 Responders High MYC activity leads to PD-(L)1 resistance and immune suppressed TME through:1,2 Active MYC1 Anti-PD1 Resistant immune • Increased PD-L1 expression suppressed2 • Decreased Type I IFN • Exclus
Slide 15: Conclusions
Conclusions • ENT + PEMBRO demonstrated durable antitumor activity (ORR 10%) in patients with NSCLC who have progressed on prior PD-(L)1 blockade • Exploratory biomarker analyses identified baseline levels of peripheral classical monocytes as potential predictors of clinical benefit ‒ Patients with
Slide 16: Acknowledgments
Acknowledgments The authors thank the patients and their families, investigators and study staff This study was sponsored by Syndax Pharmaceuticals, Inc., in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Editorial assistance was provided by Blu
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