Syndax Pharmaceuticals, Inc. · NASDAQ:SNDX

Syndax Pharmaceuticals — Technical Presentation (April 2018)

15 slides from Syndax Pharmaceuticals's technical presentation, Apr 15, 2018

  1. Slide 1: Safety, Efficacy, and Immune Correlates of Alternative Doses and Schedules of Entinostat With Pembrolizumab

    Safety, Efficacy, and Immune Correlates of Alternative Doses and Schedules of Entinostat Combined With Pembrolizumab in Patients With Advanced Solid Tumors – Results From SNDX-275-0141 Phase I Trial Anthony Tolcher1,7, Michael L. Meyers2, Dmitry Gabrilovich3, Fang Wang3, Jane Trepel4, Min-Jung Lee4,

  2. Slide 2: Disclosure Information: AACR Annual Meeting 2018

    Disclosure Information: AACR Annual Meeting 2018 Anthony W. Tolcher MD, FRCPC, FACP I have the following financial relationships to disclose:  Grant/Research support from Syndax for the conduct of this study  Employee of: Past Employment at START, now NEXT Oncology  I will discuss the following o

  3. Slide 3: Immune Checkpoint Inhibitors & Entinostat Target Complementary Immunosuppression Mechanisms

    Immune Checkpoint Inhibitors & Entinostat Target Complementary Immunosuppression Mechanisms in the Tumor Microenvironment  Entinostat – oral, class I selective histone deacetylase inhibitor  Has demonstrated potent immunomodulatory activity by inhibition of myeloid-derived suppressor cell (MDSC) f

  4. Slide 4: Overview of Study 0141 Design and Schedule of Blood Samples

    Overview of Study 0141 Design and Schedule of Blood Samples Alternative doses were hypothesis generating Part 1 Double Blind Part 2 ARM A Entinostat 1mg daily (Days 1-5 every 7 days) R Entinostat 15mg R + pembrolizumab 200 mg Q3W A Single dose A (N=10) N (N=15) N Patients D D ARM B with advanced O 2

  5. Slide 5: Baseline Demographics of Treatment Arms Are Similar

    Baseline Demographics of Treatment Arms Are Similar Arm A 1 mg Days 1-5 Arm B Arm C every 7 5 mg weekly 10 mg QoW Total (N=8) (N=9) (N=9) (N=26) Age (years), median (range) 59.5 (22 - 68) 56.0 (44 -75) 65.0 (41-70) 60.5 (22-75) Sex, n (%) Male 2 ( 25.0) 2 ( 22.2) 3 ( 33.3) 7 ( 26.9) Female 6 ( 75.0)

  6. Slide 6: Hypothesis: Myeloid Derived Suppressor Cells Mediate Resistance to PD1 axis targeting

    Principal Biomarker Correlates Hypothesis: Myeloid Derived Suppressor Cells Mediate Resistance to PD1 axis targeting  Determine the effect on MDSC population in blood after exposure to entinostat or placebo in the lead-in portion of the study  Determine the effect of MDSC population in blood after

  7. Slide 7: Immune (MDSC) Biomarkers Were Analyzed at Four Timepoints

    Immune (MDSC) Biomarkers Were Analyzed at Four Timepoints Sample Sample (before dosing) Sample (before dosing) Sample Day 1 Day 14 Day 1 Day 15 Randomize: Randomize:  15 mg entinostat  Arm A – 1 mg entinostat, Days 1-5 every 7 days  Placebo  Arm B – 5 mg entinostat weekly  Arm C – 10 mg entinos

  8. Slide 8: Lead-in Shows MDSCs Are Significantly Lowered by Entinostat Compared to Placebo

    Lead-in Shows MDSCs Are Significantly Lowered by Entinostat Treatment Compared to Placebo MDSC Lin-/CD14+/HLA-DRlow/neg 60 p = 0.0039*  After a single entinostat dose, MDSC cell frequency was significantly decreased in patients who received entinostat compared to placebo 30 MDSC Change, % (Post-dos

  9. Slide 9: Lead-in Shows MDSCs Are Significantly Lowered by Entinostat Compared to Placebo

    Lead-in Shows MDSCs Are Significantly Lowered by Entinostat Treatment Compared to Placebo Entinostat Placebo 30 30 20 20 (% Cells) (% Cells) MDSC MDSC 10 10 p = 0.0069** p = 0.636** 0 0 Pre-dose Post-dose Pre-dose Post-dose 9 ** Paired t-test.

  10. Slide 10: In Part 2, Continuous Dosing Maintains Observed Decrease in MDSCs

    In Part 2, Continuous Dosing Maintains Observed Decrease in MDSCs – (141) C1D15 Placebo Primed Entinostat Primed 60 60 MDSC Change, % MDSC Change, % (Post-dose – Pre-dose) (Post-dose – Pre-dose) 30 30 0 0 -30 -30 -60 -60 1 mg 5 mg 10 mg 1 mg 5 mg 10 mg Dose Group Dose Group Entinostat Dosing Arms: 

  11. Slide 11: Entinostat Pharmacokinetics Contribute to Durable Exposure

    Entinostat Pharmacokinetics Contribute to Durable Exposure 1 mg 5 mg 10 mg 15 mg C max AUC(Cycle 1) Cmax ng/mL 9 52 118 253 800 20000 AUC(cycle1) ng*hr/mL 1040 1366 2432 6359 Entinostat PK 600 15000 1000 15 mg (-0140) Entinostat Cp (ng/mL) ng*hr/mL 10 mg (-0141) ng/mL 10000 100 5 mg (-0141) 400 1 mg

  12. Slide 12: A Similar Safety Profile Is Observed As Previously Reported

    A Similar Safety Profile Is Observed As Previously Reported1,2 – Grade 3/4 Related Adverse Events Total  No notable differences in the safety (N=26) profile were observed among the 3 arms Subjects With At Least One Grade >= 3 10 (38.5) Related Treatment-Emergent Adverse Event Neutrophil count decre

  13. Slide 13: Entinostat + Pembrolizumab Shows Promising Activity In Heavily Pretreated Cancers

    Entinostat + Pembrolizumab Shows Promising Activity In Patients with Heavily Pretreated Cancers Endometrial 10 mg QoW Breast Ovarian Breast Breast Encouraging activity: NSCLC Prostate  3 PRs (ORR = 11.5%) Uterine in endometrial, HR+ Prostate BC, uterine Breast Uterine leiomyosarcoma 5 mg QW Cervica

  14. Slide 14: Conclusions

    Conclusions  Consistent with previous reports, entinostat treatment results in reductions in circulating MDSCs  No notable differences in the safety profile were observed among the 3 arms, and the overall safety profile was consistent with previously reported experience of entinostat combined with

  15. Slide 15: Acknowledgements

    Acknowledgements  We thank the patients and their families/caregivers  START study staff This study was sponsored by Syndax Pharmaceuticals, Inc., in collaboration with Merck & Co., Inc., Kenilworth, NJ 15

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