Curis, Inc. · NASDAQ:CRIS
Curis — Investor Presentation (August 2010)
35 slides from Curis's investor presentation, Aug 11, 2010
Slide 1: Corporate Presentation
Corporate Presentation August 11, 2010 NASDAQ: CRIS
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: Curis Pipeline: A Balanced Model
Curis Pipeline: A Balanced Model Early Mid Late Discovery preclinical preclinical preclinical IND I II III NDA Products GDC-0449/RG3616 (Hedgehog pathway inhibitor) Phase I expansion Phase cohort II Cancer Advanced basal cell carcinoma Preclinical Pivotal Phase II (1) Phase II* GDC-0449/RG3616 (Hedg
Slide 4: Key Near-Term Milestones Across all Programs
Key Near-Term Milestones Across all Programs Summary of Next Data and Development Objectives 2010E 2011E GDC-0449 Hedgehog Pathway Inhibitor Advanced Ovarian Evaluation of Phase Phase II II Results Ongoing Advanced BCC Pivotal Pivotal Phase II Data NDA Submission Phase II Operable FPI BCC Phase II P
Slide 5: Hedgehog-Associated Cancers
Hedgehog-Associated Cancers Mutation Driven Ligand Driven Basal Cell Carcinoma Ovarian Cancer Medulloblastoma Pancreatic Carcinoma Rhabdomyosarcoma Small Cell Lung Cancer Stomach Cancer Esophageal Cancer Prostate Cancer Breast Cancer Liver Cancer 5
Slide 6: 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 6
Slide 7: Abnormal Hedgehog Expression: Network Disruption
Abnormal Hedgehog Expression Supports Growth of Certain Cancers: Network Disruption Certain Cancers Hedgehog GDC-0449 Protein Adjacent Stromal Cells Angiogenesis Factors Growth Factors VEGF, Ang-1, Ang-2 IGF-I,BDNF, NGF 7
Slide 8: Phase II Clinical Trial Status
Phase II Clinical Trial Status Patient Advanced Basal Cell Operable Basal Cell Ovarian Cancer First-Line Metastatic Population Carcinoma Carcinoma Maintenance Therapy Colorectal Cancer Phase Pivotal Phase II Phase II Prep Phase II Phase II # Patients N = 100 N = ~50 N = 104 N = 199 Design Single ARM
Slide 9: Hedgehog-Associated Cancers
Hedgehog-Associated Cancers Mutation Driven Ligand Driven Basal Cell Carcinoma Ovarian Cancer Medulloblastoma Pancreatic Carcinoma Rhabdomyosarcoma Small Cell Lung Cancer Stomach Cancer Esophageal Cancer Prostate Cancer Breast Cancer Liver Cancer 9
Slide 10: GDC-0449 Demonstrated Clinical Benefit in BCC Patients in Phase I
GDC-0449 Demonstrated Clinical Benefit in BCC Patients in Phase I Clinical Trial Best Response Patients, N=33 Complete Response 2 (6.1%) Partial Response 16 (48.5%) Stable Disease 11 Disease Progression 4 Imaging 8* Clinical Examination 10 Duration on Study (median) 9.8+ months Duration of Response
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 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 2009 11
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 Baseline At 8 months (confirmed PR) 67 year old with BCC Metastatic to Lung, Liver and Bone Von Hoff, et al., Presented at American Association for Cancer Research Annual Meeting 2008 12
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 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 2008 13
Slide 14: BCC Patients Phase I Safety Summary
BCC Patients Phase I Safety Summary • No grade 5 toxicities or dose-limiting toxicities observed • Single grade 4 adverse event not determined to be related to the study drug • Grade 3 adverse events included ─ fatigue (n=4), hyponatremia (n=2), weight loss (n=2), dyspnea (n=2) ─ 1 patient each musc
Slide 15: Curis Pipeline: A Balanced Model
Curis Pipeline: A Balanced Model Early Mid Late Discovery preclinical preclinical preclinical IND I II III NDA Products GDC-0449/RG3616 (Hedgehog pathway inhibitor) Phase I expansion Phase cohort II Cancer Advanced basal cell carcinoma Preclinical Pivotal Phase II (1) Phase II* GDC-0449/RG3616 (Hedg
Slide 16: CUDC-101 Drug Design and Mechanism of Action
CUDC-101 Drug Design and Mechanism of Action: Enhance Efficacy and Overcome Resistance to EGFR/Her2 Inhibitors 16
Slide 17: Limitation of Single-Target Drug, such as Erlotinib and Other RTK Inhibitors
Limitation of Single-Target Drug, such as Erlotinib and Other RTK Inhibitors - Limited Response Rate and Drug Resistance Adaptation & RTK Further Mutation Sensitive Further Mutations EGFR-T790M EGFR-L858R (or activating mutation) HER2/HER3 MET Erlotinib Erlotinib Erlotinib Akt MAPK Akt MAPK Akt MAPK
Slide 18: CUDC-101 Structure Design
CUDC-101 Structure Design: Integrating a hydroxamic acid HDAC-inhibiting moiety into quinazoline RTK inhibition pharmacophore HDAC Inhibitors EGF/Her2 Inhibitors H N CH O O H3C O N N O SAHA N erlotinib MW 264.3 O H3C O O N MW 393.5 O F O N Cl Belinostat S N lapatinib O N MW 318.35 H3 C O MW 581.1 N
Slide 19: 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 • HDAC inhibition: 5-10 fold more potent than SAHA • EGFR inhibition: 10-20 fold more
Slide 20: 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 Nucleus Cytoplasm • Histones • Proteins (e.g., HSP90, tubulin) • Transcription factors ─ No inhibitory activity again
Slide 21: CUDC-101, Advantages over Single-Target Drugs
CUDC-101, Advantages over Single-Target Drugs: Disruption of Signaling Network Erlotinib Limited Response Rate Improved Response Rate CUDC-101 Drug Resistance Escape Drug Resistance EGFR-L858R EGFR HER2/HER3 MET EGFR/HER2 EGFR/HER2 Akt MAPK Akt MAPK Signaling Signaling Signaling Signaling Class II H
Slide 22: CUDC-101 Exhibits Immediate and Stable Inhibition of RTK and Akt Signaling
CUDC-101 Exhibits Immediate and Stable Inhibition of RTK and Downstream Akt Signaling Adaptation & Ctrl CUDC-101 erlotinib SAHA Further Mutations p-EGFR HER2/HER3 MET p-HER2 HER2 p-HER3 p-Akt Akt Akt MAPK Tubulin Signaling Signaling 0 2 7 24 2 7 24 24 Hrs p-Akt SAHA Tubulin Transcription p-Akt CUDC-
Slide 23: CUDC-101 Reduces Levels of Phosphorylated and Total MET
CUDC-101 Reduces Levels of Phosphorylated and Total MET Adaptation & Further Mutations H1993 NSCLC HER3 MET Ctrl CUDC-101 erlotinib SAHA Ac-Tub p-Akt Erlotinib Akt p-MET Akt MAPK Signaling Signaling MET p21 Tubulin Hrs 0 2 7 24 2 7 24 2 7 24 Transcription 23
Slide 24: The Potential of CUDC-101 to Overcome Drug Resistance through T790M Mutation
The Potential of CUDC-101 to Overcome Drug Resistance through EGFR Secondary T790M Mutation RTK Further Mutation EGFR-T790M H1975 Control CUDC-101 erlotinib 24 Hrs 0.3 1 0.3 1 M Akt MAPK EGFR Signaling Signaling WT/T790M p-Akt Akt p-MAPK Transcription MAPK Tubulin 24
Slide 25: CUDC-101 Clinical Ph I(a) Trial Summary
CUDC-101 Clinical Ph I(a) Trial Summary Status ─ Phase I Dose escalation study completed Q2 2010 Completed Progress ▪ Enrollment completed and last patient treatment completed - 25 patients enrolled to date Well Tolerated - PK75dose mg/proportional m2 150 mg/ m2 - MTD @ 275 mg/m2 - Therapeutic windo
Slide 26: Reduction in Serum Alkaline Phosphatase in Advanced Gastric Cancer Patient
Reduction in Serum Alkaline Phosphatase in a Patient with Advanced Gastric Cancer (275 mg/m2) 300 Alkaline Phosphatase (U/L) 250 200 150 100 0 20 40 60 80 100 Time On Study (Days) 26
Slide 27: Preliminary Antitumor Activity: Metastatic Salivary Cancer
Preliminary Antitumor Activity: Metastatic Salivary Cancer (Head & Neck) Mixed Response with reduction in mediastinal mass 150 mg/m2 Baseline Post 4th Cycle 27
Slide 28: Current CUDC-101 Clinical Trial Summary
Current CUDC-101 Clinical Trial Summary Completed Safety Progress ─ Dose-limiting toxicity of transient grade 2 elevated Creatinine levels observed at 300 mg/m2 Well Tolerated 75 mg/ m 2 150 mg/ m 2 ─ 75 mg/m2,150 mg/m2, 225 mg/m2, and 275mg/m2 appear well- tolerated High Exposure ▪ Most frequent ad
Slide 29: Phase Ib Expansion Trial Initiated August 2010 and Planning for Phase I/II
Phase Ib Expansion Trial Initiated August 2010 and Planning for Phase I/II Trial in Head & Neck Cancer • 40-patient Phase I(b) trial initiated in August 2010 ─ Gastric, Head & Neck, Breast and liver cancer patients ▪ ~10 patients per tumor type ─ Primary objective is to compare the safety and tolera
Slide 30: Curis Pipeline: A Balanced Model
Curis Pipeline: A Balanced Model Early Mid Late Discovery preclinical preclinical preclinical IND I II III NDA Products GDC-0449/RG3616 (Hedgehog pathway inhibitor) Phase I expansion Phase cohort II Cancer Advanced basal cell carcinoma Preclinical Pivotal Phase II (1) Phase II* GDC-0449/RG3616 (Hedg
Slide 31: Debio 0932 (formerly CUDC-305): Potential Best-in-Class HSP90 inhibitor
Debio 0932 (formerly CUDC-305): Potential Best-in-Class HSP90 inhibitor 31
Slide 32: 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 c
Slide 33: Corporate
Corporate rm CURIS. 33
Slide 34: Financial Data
Financial Data June 30, 2010 (000’s) Cash, cash equivalents, investments $ 44,900 Warrant Liability $ 1,300 Shareholders’ equity $ 51,800 Basic shares outstanding 75,600 Fully diluted shares outstanding 89,300 (1) 2010 year-to-date net income $ 2,700 (1) Fully diluted shares outstanding of 89.3 mill
Slide 35: Corporate Presentation
Corporate Presentation August 11, 2010 NASDAQ: CRIS