Sagimet Biosciences Inc. - Series A · NASDAQ:SGMT

Sagimet Biosciences Inc. - Series A — Sagimet Biosciences — Technical Presentation (February 2016)

13 slides from Sagimet Biosciences Inc. - Series A's technical presentation, Feb 24, 2016

  1. Slide 1: Sebum Analysis from Dose Escalation and Expansion Phases of the FASN Inhibitor TVB-2640 Phase 1 Trial

    Sebum Analysis from Dose Escalation and Expansion Phases of the FASN Inhibitor TVB-2640 Phase 1 Trial, A Non-Invasive Biomarker of Target Engagement D. Buckley, M. O’Farrell, R. Crowley, M. Fridlib, J. Waszczuk, T. Heuer, W. McCulloch, G. Kemble 3-V Biosciences Inc., Menlo Park, CA 1 February 24, 20

  2. Slide 2: FASN: A Well-Credentialed Target in Oncology

    FASN: A Well-Credentialed Target in Oncology Ø Fa#y acid synthase (FASN) levels increased in tumors, especially in later stage disease Ø High FASN levels predict mortality in several FASN Expression Correlates with Poorer Survival in NSCLC Patients cancers including NSCLC 1.0 Ø High blood FASN le

  3. Slide 3: TVB-2640: A Novel FASN Inhibitor with Excellent Human Exposure

    TVB-2640: A Novel FASN Inhibitor with Excellent Human Exposure Ø TVB-­‐2640 FASN inhibitor 100000" § First in class § Potent 10000" TVB$2640)(ng/ml)) § Highly selecCve 1000" § Reversible 100" 240"mg/m2" 10" 120"mg/m2" 60"mg/m2" 1" 0" 4" 8" 12" 16" 20" 24" Ø PharmacokineCcs in human Time)(hr))

  4. Slide 4: CLIN-002: A Phase 1 Study of TVB-2640 in Human Subjects with Advanced-Stage Solid Tumors

    CLIN-002: A Phase 1 Study of TVB-2640 in Human Subjects with Advanced-Stage Solid Tumors Ø Design § Oral, once daily; DLT period 21 days (monotherapy) or 28 days (with paclitaxel); con@nuous cycles § Adult pa@ents (ECOG 0-­‐1), with pathologically confirmed metasta@c or advanced-­‐stage solid tumo

  5. Slide 5: TVB-2640 PD Activity in Patient Tumor and Serum Previously Demonstrated

    TVB-2640 PD Activity in Patient Tumor and Serum Previously Demonstrated Serum Metabolomic analysis shows increased malonyl carnitine from substrate buildup and decreased palmitate containing lipids TVB-2640 Acetyl-CoA FASN Palmitate in complex lipids Malonyl-CoA Malonyl Carnitine ≥5-Fold Gene5-fold

  6. Slide 6: Sampling Forehead Sebum with Sebutape

    Sampling Forehead Sebum with Sebutape® Why study sebum? Ø Lipid composition suggests high FASN activity Ø Easily accessed, high patient compliance Ø Completely non-invasive sampling Ø Potential for a rapid quantitative assay of TVB-2640 activity in human subjects 6

  7. Slide 7: Sebaceous Gland Secretion

    Sebaceous Gland Secretion Ø Sebum secreCon by holocrine producCon – release of enCre cellular contents by lysis of the sebocyte Ø Transit Cme for holocrine secreCon in man ~1 week Ø Both dietary fa#y acids and newly synthesized lipids are incorporated into sebum Sebum Composition M Picardo , M Ot

  8. Slide 8: Sebutape Analysis Method

    Sebutape® Analysis Method TRUEMASS® SEBUM LIPID PANEL COMPLETE ANALYSIS OF LIPID CLASS CONCENTRATION AND COMPOSITION EXTRACTION SEPARATION OF FATTY ACID ANALYSIS QUANTITATIVE IS ADDITION LIPID CLASSES OF EACH LIPID DATA REPORT CLASS Reprinted with permission Metabolon® 8

  9. Slide 9: Sebum-specific Lipid Sapenic Acid (16:1, n-10) in TG

    Sebum-specific Lipid Sapenic Acid (16:1, n-10) in TG Sapenic Acid is an immediate downstream derivative of palmitate (FASN) TVB-2640 Effects on Sebum-specific Sapenic acid TG 200 Sapenic Acid TG Saturated+monounsaturated TG nmoles per sebutape nmoles per sebutape 600 150 400 100 200 50 0 0 0 8 22 43

  10. Slide 10: TVB-2640 Monotherapy – Sebum Triglycerides

    TVB-2640 Monotherapy – Sebum Triglycerides C1D1 Lipidomic profiling of TVB-2640 C1D2 Once daily C1D8 sebum, >30 readouts CXD1 TVB-2640 Effects on Sebum Saturated and Monounsaturated Triglycerides Lipid Reduction at C1D8 vs. C1D0 Treated vs. Control p<0.0001 SD Patients PD Patients Normals (untreated

  11. Slide 11: TVB-2640 - Persistent Inhibition of Lipogenesis

    TVB-2640 - Persistent Inhibition of Lipogenesis >30 Weeks in a NSCLC Patient - KRASmut Saturated and monounsaturated TG in Sebum 800 nmoles per sebutape 600 400 200 0 0 50 100 150 200 Days on Study 11

  12. Slide 12: Summary and Conclusions

    Summary and Conclusions Ø Sebum analysis provides a non-­‐invasive measure of TVB-­‐2640 PD acCvity in paCents Ø TVB-­‐2640 causes significant inhibiCon of de novo lipogenesis by sebocytes Ø Sebum lipid producCon was significantly reduced aFer 7 days exposure to TVB-­‐2640 Ø No obvious sebum differ

  13. Slide 13: Acknowledgments

    Acknowledgments The authors gratefully acknowledge the contribuCons of: Ø The paCents, families and invesCgators who have parCcipated in the CLIN-­‐002 Trial Ø The Lipidomics Group at Metabolon for performing the sebum lipid analysis Ø The team at 3V Biosciences 13

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