Curis, Inc. · NASDAQ:CRIS

Curis — ASCO Annual Meeting 2013

12 slides from Curis's conference presentation, Jun 4, 2013

  1. Slide 1: Phase I Study of Safety and Pharmacokinetics of GDC-0917

    1 Phase I Study of Safety and Pharmacokinetics of GDC-0917, an Antagonist of Inhibitor of Apoptosis Proteins in Patients with Refractory Solid Tumors or Lymphoma A Tolcher,1 K Papadopoulos,1 A Patnaik,1 WJ Fairbrother,2 H Wong,2 N Budha,2 WC Darbonne,2 F Peale,2 M Mamounas,2 S Royer-Joo,2 R Yu,2 CC

  2. Slide 2: IAP antagonists promote cell death through both intrinsic and extrinsic pathways

    IAP antagonists promote cell death through 2 both intrinsic and extrinsic pathways TNFα TNFR1 Extrinsic TRADD Intrinsic FADD2 TRAF2 TRAF3 BH3-only proteins RIP2 cIAPs TRAF2 NIK Bid cIAPs Bax/Bak Bcl-2/Bcl-xL/Mcl-1 Ubq Ubq Smac mimetic Caspase-8, -10 Mitochondria GDC-0917 Smac Cytochrome C mimetic GD

  3. Slide 3: IAP selective antagonist: GDC-0917

    3 IAP selective antagonist: GDC-0917 Breast cell line: MDA-MB-231.X1  GDC-0917, a Smac mimetic, binds to (10 mg/kg) (100 mg/kg) the same sites on the IAP proteins as the IAP protein-interaction motifs of Smac and caspase-9  GDC-0917 binding in vitro induces apoptosis via caspase-3 and -7 activatio

  4. Slide 4: GDC-0917 Phase I study design

    4 GDC-0917 Phase I study design  Phase I, dose-escalation study using a modified continual reassessment method (mCRM) design in patients with refractory solid tumors or lymphoma  Endpoints: − Primary: Dose-limiting toxicities (DLT, assessed D1-24), adverse events (AEs), and pharmacokinetics (PK) −

  5. Slide 5: Patient demographics and baseline characteristics

    Patient demographics and baseline 5 characteristics (N=42 patients) All patients, N (%) Age in years , median (range) 61 (36−86) Sex Female 20 (48) Male 22 (52) ECOG status 0 21 (50) 1 21 (50) Primary tumor type Breast 10 (24) Colorectal 10 (24) Prostate 6 (14) Small cell lung 4 (10) Ovarian 2 (5) O

  6. Slide 6: Treatment exposure and disposition

    6 Treatment exposure and disposition (N=42 patients) All patients, N (%) Total treated 42 (100) Extent of exposure to GDC-0917, 2 (1−15) median cycles (range) Reason for study discontinuation Disease progression 28 (67) Adverse event 7 (17) Physician decision 3 (7) Death* 2 (5) Patient decision 2 (5

  7. Slide 7: Safety summary

    7 Safety summary Safety Events Description DLTs Grade 3 fatigue (1 pt, 450 mg dose level) • Fatigue: n=9 (1 Grade 3 [DLT], 4 Grade 2, 4 Grade 1) Most frequent GDC-0917- • Nausea: n=9 (2 Grade 2, 7 Grade 1) related AEs • Rash: n=6 (1 Grade 3, 1 Grade 2, 4 Grade 1) (in > 10% of pts) • Vomiting: n=6 (6

  8. Slide 8: GDC-0917 pharmacokinetics

    8 GDC-0917 pharmacokinetics  GDC-0917 peak concentrations Tmax: 2−3h post dosing  Mean plasma elimination t1/2: 4−8h  Dose-proportional exposure with no apparent accumulation at steady state Cycle 1 mean plasma concentration-time profiles of Cycle 1 mean plasma concentration-time profiles of GDC-

  9. Slide 9: GDC-0917 pharmacodynamics

    9 GDC-0917 pharmacodynamics  Rapid down modulation of cIAP1 in PMBCs at all dose levels  Decreased cIAP1 (2 pts, at 40 and 200 mg) and increased activated caspase-3 and cPARP (1 pt at 200 mg) in tumor biopsies*  GDC-0917 dosed at 60 mg or higher resulted in a 40-70% increase in plasma MCP1 nine h

  10. Slide 10: Preliminary signs of efficacy

    10 Preliminary signs of efficacy  Two patients (4.8%) had unconfirmed complete response (uCR) 1. MALT lymphoma (300 mg): PET CR end of Cycle 5 (off study after 5 Cycles per patient’s choice) 2. Ovarian cancer (450 mg): CR end of Cycle 2 (off study after 2 Cycles due to AE), continued follow-up show

  11. Slide 11: Summary and overall conclusions

    11 Summary and overall conclusions  GDC-0917 had a favorable safety and PK profile in patients with advanced malignancies  MTD was not determined, although ED90 based on preclinical xenograft studies was reached  Pharmacodynamic modulation was observed  Antitumor activity was observed in some pa

  12. Slide 12: Acknowledgements

    12 Acknowledgements Thank you to the many patients for their participation in this trial Genentech exclusively licensed GDC-0917 to Curis, Inc. Curis designated the molecule CUDC-427 and has the sole right and responsibility for all research, development, manufacturing and commercialization activiti

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