Curis, Inc. · NASDAQ:CRIS
Curis — Investor Presentation (January 2010)
34 slides from Curis's investor presentation, Jan 8, 2010
Slide 1: Corporate Overview
Corporate Overview January 7, 2010 NASDAQ: CRIS Exhibit 99.1
Slide 2: Curis Pipeline
Multiple cancers Phase I Phase II First-line metastatic colorectal cancer Phase II Advanced ovarian cancer Phase II Phase I expansion cohort Phase II Advanced basal cell carcinoma Pivotal Phase II (1) Multiple cancers Preclinical Multiple cancers CTA Filed Curis Pipeline Discovery Products Early pre
Slide 3: Curis Pipeline
Multiple cancers Phase I First-line metastatic colorectal cancer Phase II Advanced ovarian cancer Phase II Advanced basal cell carcinoma Pivotal Phase II (1) Multiple cancers CTA Filed Multiple cancers Preclinical Curis Pipeline Discovery Products Early preclinical Mid preclinical Late preclinical I
Slide 4: Hedgehog-Associated Cancers
Hedgehog-Associated Cancers Ligand Driven Colorectal Cancer Ovarian Cancer Small Cell Lung Cancer Pancreatic Carcinoma Stomach Cancer Esophageal Cancer Prostate Cancer Breast Cancer Liver Cancer Mutation Driven Basal Cell Carcinoma Medulloblastoma Rhabdomyosarcoma
Slide 5: GDC-0449 Demonstrated Clinical Benefit in BCC Patients in Phase I Clinical Trial
Responses confirmed by Independent Review Facility; measured using RECIST criteria Genentech and Roche are responsible for the clinical development and commercialization of GDC-0449 * 1 of 8 partial responses confirmed by imaging was also confirmed by clinical examination. GDC-0449 Demonstrated Clin
Slide 6: Phase I Study of GDC-0449 in Locally Advanced, Multifocal or Metastatic BCC
Phase I Study of GDC-0449 in Locally Advanced, Multifocal or Metastatic BCC Baseline After 5 Months 60 year old with basal cell nevus syndrome with lesions of the posterior scalp Von Hoff, et al., New England Journal of Medicine, September 200 9
Slide 7: Phase I Study of GDC-0449 in Locally Advanced, Multifocal or Metastatic BCC
Phase I Study of GDC-0449 in Locally Advanced, Multifocal or Metastatic BCC 67 year old with BCC Metastatic to Lung, Liver and Bone Von Hoff, et al., Presented at American Association for Cancer Research Annual Meeting 200 8 Baseline At 8 months (confirmed PR)
Slide 8: Phase I Study of GDC-0449 in Locally Advanced, Multifocal or Metastatic BCC
Phase I Study of GDC-0449 in Locally Advanced, Multifocal or Metastatic BCC Baseline After 2 Months 83 year old with BCC Lesion Invasive in Ear and Parotid Gland Von Hoff, et al., Presented at American Association for Cancer Research Annual Meeting 200 8
Slide 9: Hedgehog-Associated Cancers
Hedgehog-Associated Cancers Ligand Driven Colorectal Cancer Ovarian Cancer Small Cell Lung Cancer Pancreatic Carcinoma Stomach Cancer Esophageal Cancer Prostate Cancer Breast Cancer Liver Cancer Mutation Driven Basal Cell Carcinoma Medulloblastoma Rhabdomyosarcoma
Slide 10: Abnormal Hedgehog Expression Supports Growth of Certain Cancers
Certain Cancers Abnormal Hedgehog Expression Supports Growth of Certain Cancers Hedgehog Protein Adjacent Stromal Cells Angiogenesis Factors VEGF, Ang-1, Ang-2 Growth Factors IGF-I, BDNF, NGF
Slide 11: Shh Induces Angiogenesis
Shh Day 0 Shh Day 6 Shh Induces Angiogenesis day 0 day 6 pellet containing Shh
Slide 12: Abnormal Hedgehog Expression Supports Growth of Certain Cancers: Network Disruption
Abnormal Hedgehog Expression Supports Growth of Certain Cancers: Network Disruption Adjacent Stromal Cells Angiogenesis Factors VEGF, Ang-1, Ang-2 Growth Factors IGF-I, BDNF, NGF GDC-0449
Slide 13: Phase II Clinical Trial Status
Phase II Clinical Trial Status Patient Population Advanced Basal Cell Carcinoma (Mutation-Driven) First-Line Metastatic Colorectal Cancer (Li g and-Driven) Advanced Ovarian Cancer Maintenance Therapy (Li g and-Driven) Phase Pivotal Phase II Phase II Phase II # Patients N = 100 N = 190 N = 100 Design
Slide 14: Curis Pipeline
Multiple cancers Phase I First-line metastatic colorectal cancer Phase II Advanced ovarian cancer Phase II Advanced basal cell carcinoma Pivotal Phase II (1) Phase II* Multiple cancers CTA Filed Multiple cancers Preclinical Curis Pipeline Discovery Products Early preclinical Mid preclinical Late pre
Slide 15: Curis Multi-Targeted Inhibitor Cancer Platform: Designed for Network Disruption
EGFR inhibitor HDAC Her2 inhibitor inhibitor CUDC-101 EGFR Inhibition HDAC Inhibition Her2 Inhibition Rational Desi g n Sin g le Small Molecule M.W. < 500 Curis Multi-Targeted Inhibitor Cancer Platform: Designed for Network Disruption
Slide 16: Limitation of Single-Target Drugs, such as Erlotinib and other RTK inhibitors
Resistance via mutation Response Resistance via adaptation Poor Response Rate and Drug Resistance HER3 MET MAPK Signaling Akt Signaling Transcription Regulation Transcription Regulation Transcription Regulation Limitation of Single-Target Drugs, such as Erlotinib and other RTK inhibitors
Slide 17: Rationale for Multi-Targeted Inhibitors of HDAC and Receptor Tyrosine Kinases
Rationale for Multi-Targeted Inhibitors of HDAC and Receptor Tyrosine Kinases • Dysregulation of histone deacetylase (HDAC) activity plays a role in tumor onset and tumor pro g ression • HDAC inhibitors suppress tumor cell g rowth/survival via: - Histone acetylation to reverse aberrant epigenetic ch
Slide 18: CUDC-101
CUDC-101 MW 434.5 erlotinib MW 393.5 lapatinib MW 581.1 CUDC-101 Structure Design: integrating a hydroxamic acid HDAC - inhibiting moiety into quinazoline RTK inhibition pharmacophore N O N O O SAHA MW 264.3 Belinostat MW 318.35 JNJ-16241199 MW 413.45 gefitinib MW 446.9 HDAC Inhibitors EGF/Her2 Inhi
Slide 19: CUDC-101 is a Very Potent and Selective HDAC, EGFR and Her2 Inhibitor
Compound IC 50 (nM) in Enzyme Assays HDAC EGFR HER2 CUDC-101 is a Very Potent and Selective HDAC, EGFR and Her2 Inhibitor SAHA 40.0 NA NA erlotinib NA 48.0 134.5 lapatinib NA 11.2 10.2 CUDC-101 4.4 2.4 15.7 Potency • HDAC inhibition: 5-10 fold more potent than SAHA • EGFR inhibition: 10-20 fold more
Slide 20: CUDC-101 Forms Additional Hydrogen Bonds with EGFR vs. Erlotinib
CUDC-101 Forms Additional Hydrogen Bonds with EGFR vs. Erlotinib • Compared to erlotinib, CUDC-101 has 20x higher binding affinity for EGFR (2.4 nM versus nM IC ); This may be explained by the additional hydrogen bond interaction of CUDC-101 with D831 in the activation loop (A-loop) CUDC-101 in EGFR
Slide 21: CUDC-101 Is A Pan Class I & II HDAC Inhibitor
CUDC-101 Is A Pan Class I & II HDAC Inhibitor - No inhibitory activity against class III HDACs (SIRT 1-3) (IC50 in nM) HDAC1 HDAC2 HDAC3 HDAC8 HDAC4 HDAC5 HDAC6 HDAC7 HDAC9 HDAC10 4.5 12.6 9.1 79.8 13.2 11.4 5.1 67.2 26.1 Class I Class II Nucleus • Histones • Transcription factors Cytoplasm • Protei
Slide 22: CUDC-101, Advantages Over Single-Target Drugs: Disruption of Signaling Network
Poor Response Rate Drug Resistance Improved Response Rate Escape Drug Resistance EGFR/Her2 HER3 MET Class II HDAC Class I HDAC EGFR/HER2 CUDC-101 EGFR/HER2 Erlotinib Lapatinib EGFR/Her2 HER3 MET Transcription Regulation Transcription Regulation MAPK Signaling Akt Signaling MAPK Signaling Akt Signali
Slide 23: CUDC-101 Synergistically Suppresses HER2 Signaling Through Multiple Points of Intervention
HSP90 Class II HDAC Class I HDAC EGFR/HER2 Her2 GAPDH M 0 1 5 10 1 5 10 1 10 -RT ctrl CUDC-101 SAHA lapatinib HER2 p-Akt GAPDH Control CUDC-101 p-HER2 HER2 CUDC-101 Synergistically Suppresses HER2 Signaling Through Multiple Points of Intervention
Slide 24: Reduction in Serum Alkaline Phosphatase in a Patient with Advanced Gastric Cancer
Reduction in Serum Alkaline Phosphatase in a Patient with Advanced Gastric Cancer (275 mg/m ) Time On Study (Days)
Slide 25: Preliminary Antitumor Activity: Metastatic Salivary Cancer (Head & Neck)
Mixed Response with reduction in mediastinal mass 150 mg/m 2 Baseline Post 4 th Cycle Preliminary Antitumor Activity: Metastatic Salivary Cancer (Head & Neck)
Slide 26: Curis Pipeline
Multiple cancers Phase I First-line metastatic colorectal cancer Phase II Advanced ovarian cancer Phase II Phase II Pivotal Phase II (1) Phase II Multiple cancers CTA Filed Phase II Phase II* Multiple cancers Preclinical Advanced basal cell carcinoma Curis Pipeline Discovery Products Early preclinic
Slide 27: Debio 0932 Summary
Debio 0932 Summary Exclusive worldwide license with Debiopharm Group in August 2009 - Monetized asset for runway extension and to further balance model - Upfront, early and subsequent clinical development milestones Total potential payments of $90 million assuming the successful achievement of clini
Slide 28: Corporate
Corporate
Slide 29: Corporate Development Pipeline: Primary Value Drivers and Capital Access
CUDC-101 Multiple Cancers Phase I 2012E 2010E 2011E CUDC-305 IND GDC-0449 Colorectal Phase II GDC-0449 BCC Pivotal Phase II GDC-0449 Ovarian Phase II 4Q 2009 GDC-0449 Seven Indications Phase I – Phase II Corporate Development Pipeline: Primary Value Drivers and Capital Access Phase Ia Completed Init
Slide 30: Financial Data
Financial Data Cash, cash equivalents, investments $ 27,200 Debt $ - Shareholders’ equity $ 34,400 Basic shares outstanding 66,500 Fully diluted shares outstanding 80,700 2009 net loss $ 7,100 Remaining warrants under August 2007 financing have been or are expected to be exercised under the terms of
Slide 31: CUDC-101 Is More Potent Than Erlotinib, Lapatinib, or Vorinostat Against a Wide Range of Human Cancer Cell Lines
CUDC-101 Is More Potent Than Erlotinib, Lapatinib, or Vorinostat Against a Wide Range of Human Cancer Cell Lines Prostate (3) Sarcoma (3) Liver (3) NSCLC (10) Ovarian (2) Pancreatic (6) Breast (5) Colon (3) Glioblastoma (3) H&N (7) IC50 (anti-proliferation assay) 10 nM 100 nM 1 uM 10 uM Vorinostat C
Slide 32: CUDC-101 Disrupts Signaling Network to Improve the Treatment of Drug-Resistant Tumors
CUDC-101 Disrupts Signaling Network to Improve the Treatment of Drug - Resistant Tumors Days Vehicle CUDC-101 120 mg/kg P<0.0001 Days P<0.0001 P<0.0001 P<0.0001 Vehicle (Captisol®) Vehicle (Captisol®) CUDC-101 (120 mg/kg) CUDC-101 (120 mg/kg) CUDC-101 & Paclitaxel CUDC-101 & Paclitaxel Paclitaxel (1
Slide 33: CUDC-101 Disrupts Signaling Network to Improve the Treatment of Heterogeneous and Drug-Resistance Tumors
EGFR HER2 HER3 MET p-Akt p53 ER HIF-1 CUDC-101 SAHA erlotinib ER- HIF-1 Tubulin Hr 0 2 7 24 2 7 24 24 Ctrl CUDC-101 erlotinib SAHA p-Akt Akt Tubulin Ac-p53 p53 P-EGFR p-HER2 HER2 P-HER3 Tubulin Ctrl CUDC-101 erlotinib SAHA Hr 0 7 18 24 Hr 0 2 7 24 2 7 24 Ctrl CUDC-101 erlotinib p-MET MET Tubulin Hr
Slide 34: Corporate Overview
Corporate Overview January 7, 2010 NASDAQ: CRIS