Curis, Inc. · NASDAQ:CRIS
Curis — Investor Presentation (October 2008)
42 slides from Curis's investor presentation, Oct 31, 2008
Slide 1: Corporate Presentation
NASDAQ: CRIS Corporate Presentation October 31, 2008 1
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains statements about Curis’ future expectations, plans and prospects that constitute forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially f
Slide 3: The Curis Model: Seeking to Develop Next Generation Targeted Cancer Drugs
The Curis Model: Seeking to Develop Next Generation Targeted Cancer Drugs GDC-0449, first-in-class Hedgehog pathway inhibitor drug candidate Developed in collaboration with Genentech Phase II testing initiated by Genentech in 2008 Proprietary platform of next generation multi-targeted small molecule
Slide 4: Curis Pipeline
Curis Pipeline Early Mid Late Discovery preclinical preclinical preclinical IND- I II III NDA Products GDC-0449 (Hedgehog pathway inhibitor) with Avastin and Phase Chemotherapy II Cancer metastatic colorectal cancer First-line Preclinical Phase II Phase II* GDC-0449 (Hedgehog pathway inhibitor) Phas
Slide 5: Curis Pipeline
Curis Pipeline Early Mid Late Discovery preclinical preclinical preclinical IND- I II III NDA Products GDC-0449 (Hedgehog pathway inhibitor) with Avastin and Phase Chemotherapy II Cancer metastatic colorectal cancer First-line Preclinical Phase II Phase II* GDC-0449 (Hedgehog pathway inhibitor) Phas
Slide 6: GDC-0449 Overview
GDC-0449 Overview First-in-class Hedgehog pathway inhibitor Small molecule Molecular weight 421.30 g/mol Orally available Phase II testing at daily dosing of 150 mgs Potent IC50 in Gli-Luciferase assay = ~ 3 nM Attractive PK Terminal half-life of greater than 7 days observed in Phase I trials 6 ©200
Slide 7: Hedgehog-Associated Cancers
Hedgehog-Associated Cancers Mutation Driven Ligand Driven Basal Cell Carcinoma10 Colorectal Cancer 5, 13 Medulloblastoma1 Ovarian Cancer 13 Rhabdomyosarcoma11 Small Cell Lung Cancer 2 Pancreatic Carcinoma 3,4 Stomach Cancer 4 Esophageal Cancer 4 Prostate Cancer 6,7,8 Breast Cancer 9 Liver Cancer12 1
Slide 8: Phase I Study of GDC-0449 in Advanced Basal Cell Carcinoma (BCC)
Phase I Study of GDC-0449 in Advanced Basal Cell Carcinoma (BCC) Aberrant Hh pathway activation present in the vast majority of BCCs 13 patients with BCC enrolled in either the dose escalation or expansion cohort of a Phase I clinical trial: GDC-0449 dose levels in dose escalation trial (oral dosing
Slide 9: 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 Clinical Activity Summary Best Response Patients, N=11 Partial Responses 6 Radiologic Exam 2* *Duration of response, months 9.3+, 5.6+ Clinical Exam 4 Stable Disease 4 Disease Progression 1 Total Clinical Benefit 10 (91%) *
Slide 10: 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 Baseline At 8 months (confirmed PR) Presented at American Association for Cancer Research Annual Meeting 2008 10 ©2008 Curis Inc.
Slide 11: 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 48 year old with BCC Lesions in Lung Baseline After 2 months Presented at American Association for Cancer Research Annual Meeting 2008 11 ©2008 Curis Inc.
Slide 12: 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 83 year old with BCC Lesion Invasive in Ear and Parotid Gland Baseline After 2 months Presented at American Association for Cancer Research Annual Meeting 2008 12 ©2008 Curis Inc.
Slide 13: 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 49 year old with Multiple Large, Invasive Lesions of Skin Baseline After 1 month After 2 months Presented at American Association for Cancer Research Annual Meeting 2008 13 ©2008 Curis Inc.
Slide 14: Phase I Safety Summary
Phase I Safety Summary No dose-limiting toxicities have been observed in the Phase I study Most frequently observed adverse events were generally mild to moderate and include fatigue, dysguesia (altered taste sensation), nausea, anorexia, cough, abdominal and back pain, diarrhea, hyponatremia, decre
Slide 15: Hedgehog-Associated Cancers
Hedgehog-Associated Cancers Mutation Driven Ligand Driven Basal Cell Carcinoma10 Colorectal Cancer 5, 13 Medulloblastoma1 Ovarian Cancer 13 Rhabdomyosarcoma11 Small Cell Lung Cancer 2 Pancreatic Carcinoma 3,4 Stomach Cancer 4 Esophageal Cancer 4 Prostate Cancer 6,7,8 Breast Cancer 9 Liver Cancer12 1
Slide 16: Abnormal Hedgehog Expression Supports Growth of Certain Cancers
Abnormal Hedgehog Expression Supports Growth of Certain Cancers Certain Cancers Hedgehog Protein Adjacent Stromal Cells Angiogenesis Factors Growth Factors VEGF, Ang-1, Ang-2 IGF-I,BDNF, NGF 16 ©2008 Curis Inc.
Slide 17: Abnormal Hedgehog Expression Supports Growth of Certain Cancers
Abnormal Hedgehog Expression Supports Growth of Certain Cancers Certain Cancers GDC-0449 Hedgehog Protein Adjacent Stromal Cells Angiogenesis Factors Growth Factors VEGF, Ang-1, Ang-2 IGF-I,BDNF, NGF 17 ©2008 Curis Inc.
Slide 18: Phase II Clinical Trial Status
Phase II Clinical Trial Status Patient First-line Metastatic Advanced Basal Advanced Ovarian Population Colorectal Cancer Cell Cancer Carcinoma Phase Phase II Phase II Phase II # Patients N = 150 TBA N = 100 Design FOLFOX or FOLFIRI chemotherapy TBA Single agent in ovarian with Avastin +/_ GDC-0449
Slide 19: Curis Pipeline
Curis Pipeline Early Mid Late Discovery preclinical preclinical preclinical IND- I II III NDA Products GDC-0449 (Hedgehog pathway inhibitor) with Avastin and Phase Chemotherapy II Cancer metastatic colorectal cancer First-line Preclinical Phase II Phase II* GDC-0449 (Hedgehog pathway inhibitor) Phas
Slide 20: The Challenge of Targeted Therapies
The Challenge of Targeted Therapies Receptor Tyrosine Kinase (RTK) inhibitors have become important therapeutic agents against various solid tumor cancers, but tumor resistance mechanisms often limit efficacy A major cause of RTKi-drug resistance appears to be survival pathways that protect against
Slide 21: Curis Multi-Targeted Inhibitor Cancer Platform
Curis Multi-Targeted Inhibitor Cancer Platform Compound Medchem Confirmatory Tumor DM/PK Efficacy Non-GLP IND IND Filing Phase I Design (SAR) in vitro Cell Safety Enabling assays Assays Studies CUDC-101 HDAC/EGFR/Her2 HDAC/BCR- Abl/Src HDAC/Hsp90 HDAC/Aurora HDAC/CDK2 HDAC/VEGFR2 HDAC/VDA HDAC/EGFR/
Slide 22: CUDC-101 Is Designed To Inhibit Simultaneously Three Clinically Validated Cancer Targets
CUDC-101 Is Designed To Inhibit Simultaneously Three Clinically Validated Cancer Targets: HDAC, EGFR & Her2 Multiple, Synergistic Target Inhibition SAHA/Vorinostat Erlotinib Lapatinib CUDC-101 (Zolinza) (Tarceva) (Tykerb) HDAC HDAC EGFR EGFR EGFR MW =264.3 MW = 393.4 HER2 HER2 MW = 581.1 MW = 434.5
Slide 23: CUDC-101 is a Very Potent and Selective HDAC, EGFR and Her2 Inhibitor
CUDC-101 is a Very Potent and Selective HDAC, EGFR and Her2 Inhibitor IC50 (nM) in Enzyme Assays Compound HDAC EGFR HER2 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 (low nM) HDAC inhibition: 5-10 fold more potent than SAHA EGFR inhibition: 10-20 fold
Slide 24: CUDC-101 Is More Potent Than Erlotinib, Lapatinib, or SAHA
CUDC-101 Is More Potent Than Erlotinib, Lapatinib, or SAHA Against a Wide Range of Human Cancer Cell Lines 10 nM 10 nM IC50 (anti-proliferation assay) CUDC-101 averages: 15x more potency than SAHA 20x more potency than Lapatinib 69x more potency than Erlotinib 100nM 100 nM Potency CUDC-101 CUDC-101
Slide 25: CUDC-101 Is More Potent Than a Combination of SAHA/Erlotinib or SAHA/Lapatinib
CUDC-101 Is More Potent Than a Combination of SAHA/Erlotinib or SAHA/Lapatinib Against a Wide Range of Human Cancer Cell Lines 10 nM 10 nM IC50 (anti-proliferation assay) CUDC-101 averages ~8-9x more potency than: SAHA/Erlotinib in 39 of 41 cell lines SAHA/Lapatinib in 26 of 28 cell lines CUDC-101 1
Slide 26: CUDC-101 Mechanism Summary
CUDC-101 Mechanism Summary CUDC-101 inhibits both primary RTK targets and multiple secondary targets considered important for improving multi- targeted therapeutic approaches in cancer Direct Targets Downstream/Epigenetic Targets pHer3 CUDC-101 HDAC (Class I & II) pAKT Her2 transcription Her2 protei
Slide 27: CUDC-101 Is A Pan Class I & II HDAC Inhibitor
CUDC-101 Is A Pan Class I & II HDAC Inhibitor (IC50 in nM) Class I Class II HDAC1 HDAC2 HDAC3 HDAC8 HDAC4 HDAC5 HDAC6 HDAC7 HDAC9 HDAC10 4.5 12.6 9.1 79.8 13.2 11.4 5.1 373 67.2 26.1 HSP90 Deacetylation No inhibitory activity against class III HDACs (SIRT 1-3) 27 ©2008 Curis Inc.
Slide 28: CUDC-101 Causes Tumor Regression in Mesenchymal Triple Negative Breast Cancer Model
CUDC-101 Causes Tumor Regression in Mesenchymal Triple Negative Breast Cancer Model Tumor Line Molecular Phenotype3* Lapatinib SAHA Lapatanib + SAHA CUDC-101 Improvement in Potency MDA-MB-231 “Triple Negative”** 5.4 2.11 1.8 0.10 18X MDA-MB-468 “Triple Negative”** 3.6 5.0 1.1 0.21 5X Tumor Size Body
Slide 29: CUDC-101 and Taxol in Combination Induces Tumor Regression in Triple Negative Breast Cancer
CUDC-101 and Taxol in Combination Induces Tumor Regression in Triple Negative Breast Cancer Xenograft Model 200 Tumor Size 120 Body Weight Vehicle: Captisol Vehicle: Captisol 180 CUDC-101 120 mg/kg CUDC-101 120mg/kg Taxol 12.5mg/kg Taxol 12.5 mg/kg Body Weight Change (%) CUDC-101 & Taxol 160 CUDC-10
Slide 30: CUDC-101 Activity Against NSCLC Cancer Models
CUDC-101 Activity Against NSCLC Cancer Models (vs. Erlotinib and/or SAHA) IC50 in M 30 ©2008 Curis Inc.
Slide 31: CUDC-101 Induces Tumor Regression in HepG2 Liver Cancer Model
CUDC-101 Induces Tumor Regression in HepG2 Liver Cancer Model CUDC-101 CUDC-101 Improved Improved Cancer. SAHA & SAHA & Potency vs. Potency vs. Type HNC Cell Line SCC-15 Phenotype SAHA 2.49 Erlotinib 1.94 Erlotinib 0.30 Lapatinib 0.64 Lapatinib 0.24 CUDC-101 0.07 S & E4X S & L3X Liver Sk-Hep-1 P53(w
Slide 32: CUDC-101 and Camptothecin-11 Induces Tumor Regression in HCT116 Colon Cancer Model
CUDC-101 and Camptothecin-11 in Combination Induces Tumor Regression in HCT116 Colon Cancer Xenograft Model Tumor Size Body Weight 400 120 Vehicle: Captisol CUDC-101 120mg/kg Vehicle: Captisol 350 CUDC-101 120mg/kg CPT11 25mg/kg CPT11 25mg/kg Body Weight Change (%) CUDC101 & CPT11 110 300 CPT11 & 68
Slide 33: CUDC-101 Potential Phase II and Commercial Market Opportunities
CUDC-101 Potential Phase II and Commercial Market Opportunities U.S.(1) Worldwide(2) Liver cancer 19,000 600,000 Non-small cell lung cancer 181,000 950,000 EGFRi resistant WT patient populations Pancreatic cancer 37,000 250,000 Colon cancer 110,000 800,000 Synergizes with Irinotecan (CPT-11), a stan
Slide 34: Advantages of Single Small Molecule Against HDAC & RTKs Vs. Two or Three Agents
Advantages of Single Small Molecule Against HDAC & RTKs Vs. Two or Three Agents Combined Combining HDAC & RTKi: Mis-matched PK (e.g., human t½ SAHA = 1.5 - 4 hrs, Erlotinib = 36 hrs) Non-optimized PD Toxicity issues More off-target toxicity and potential drug-drug interaction by two-drug combination
Slide 35: CUDC-101 Phase I Clinical Trial
CUDC-101 Phase I Clinical Trial Phase I initiated in the third quarter of 2008 3+3 dose escalating trial Initial dose is 75 mg/m2 (approximately 140 mgs in average patient) First 3-patient cohort enrolled Advanced/refractory solid tumors 18-40 subjects in 2 study centers Objectives: Primary: to esta
Slide 36: Curis Pipeline
Curis Pipeline Early Mid Late Discovery preclinical preclinical preclinical IND- I II III NDA Products GDC-0449 (Hedgehog pathway inhibitor) with Avastin and Phase Chemotherapy II Cancer metastatic colorectal cancer First-line Preclinical Phase II Phase II* GDC-0449 (Hedgehog pathway inhibitor) Phas
Slide 37: CUDC-305 Summary
CUDC-305 Summary Hsp90 inhibitor with potency comparable to leading compounds Improved tumor selectivity (vs. normal cells) High oral bioavailability (>60%) Terminal half-life of 20.5 hours in tumors vs. 6 hours in plasma Tumor regression/inhibition observed against a wide range of cancer types Upre
Slide 38: CUDC-305 Induces Complete Tumor Regression in MV4-11 AML Model
CUDC-305 Induces Complete Tumor Regression in MV4-11 Acute Myelogenous Leukemia Model Tumor Size Body Weight 1800 120 Vehicle 1600 115 CUDC-305 90 mg/kg 2-1-2 1400 CUDC-305 160 mg/kg q2d 110 1200 105 1000 100 800 95 600 p<0.0001 90 400 Vehicle CUDC-305 90 mg/kg 2-1-2 85 200 CUDC-305 160 mg/kg q2d p<
Slide 39: Anti-Tumor Activity of CUDC-305 in MDA-MB-468 Breast Cancer Xenograft Model
Anti-Tumor Activity of CUDC-305 in MDA-MB-468 “Triple Negative” Breast Cancer Xenograft Mouse Model Tumor Volume Body Weight 170 120 160 Vehicle Vehicle 115 CUDC-305 80 mg/kg qd CUDC-305 80 mg/kg qd 150 110 140 Tumor Growth (%) 105 Body Weight (%) 130 120 100 p<0.01 110 95 100 90 90 85 80 70 80 0 3
Slide 40: Financial Data
Financial Data September 30, 2008 (000’s) Cash, cash equivalents, investments (1) $ 29,900 Total liabilities $ 2,750 Debt $ - Shareholders’ equity $ 38,800 Basic shares outstanding (2) 63,400 2007 YTD loss $ (10,000) (1) Existing cash and expected $3 million milestone payment from Genentech during t
Slide 41: Upcoming Milestones
Upcoming Milestones Programs under collaboration/license GDC-0449 (Genentech) Phase II clinical trial initiation in advanced ovarian cancer in 2008 and advanced basal cell carcinoma in the first half of 2009 Curis internal programs Targeted Cancer Drug Development Platform CUDC-101 or other targeted
Slide 42: NASDAQ: CRIS Corporate Presentation
NASDAQ: CRIS Corporate Presentation October 31, 2008 42