Curis, Inc. · NASDAQ:CRIS
Curis — Investor Presentation (March 2007)
24 slides from Curis's investor presentation, Mar 9, 2007
Slide 1: Multi-Target Inhibiting Small Molecules
1 Non-Confidential Presentation March 8, 2007 Multi-Target Inhibiting Small Molecules Exhibit 99.1
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: Outline
2 Curis, Inc. Outline Novel small molecules comprise two covalently-bound pharmacophores, one targeting EGFR and the other inhibiting a second, validated cancer target (Target A) Rationale for multi-target inhibitor drugs - seeking to create “Best-in-Class” drugs Curis’ approach to cancer drug disco
Slide 4: Curis Aims to Develop Next Generation of Targeted Anticancer Drugs
3 Curis, Inc. Curis Aims to Develop Next Generation of Targeted Anticancer Drugs Targeted anticancer therapy: to target pathways and proteins involved in malignant transformation Selective kinase inhibitors are clinically efficacious and much less toxic than chemotherapy Newly approved multiple kina
Slide 5: Rationale for Designing Multi-Target Inhibitor Drugs Against Cancer
4 Curis, Inc. Rationale for Designing Multi-Target Inhibitor Drugs Against Cancer Broxterman HJ et al. Drug Resist Updat. 8:183, 2005; Budillon A et al. Curr Drug Targets 6:241, 2005 Daub H et al. Nat Rev Drug Disc 3-1001 2004; Daub H et al. Nat Rev Drug Dis 3:1001, 2004 Low risk expected Validated
Slide 6: Commercial Opportunity
5 Curis, Inc. Commercial Opportunity Datamonitor Report “Pipeline/Commercial Insight: Molecular Targeted Cancer Therapies - More drugs on the market, more targets in the pipeline”. 10/10/06 Sales of already marketed targeted cancer drugs expected to grow to $25.2 billion by 2015 (up from $7.5 billio
Slide 7: Curis' Approach to Drug Discovery
6 Curis, Inc. Curis’ Approach to Drug Discovery US operations Scientific leadership, inventorship & core competencies Compound design, in vitro assays, PK/PD, animal cancer models performed in US - tightly integrated for rapid progress Close coordination between Curis R&D and legal groups as each pr
Slide 8: Curis Drug Development Process
7 Curis, Inc. Curis Drug Development Process Curis US Cambridge, MA 1. Design compound structures 2. Submits structure for synthesis 3. Chemist synthesizes compound 4. Performs analytical analysis 5. Enters yield, purity, analytical results into database 6. Compound registered in Curis database & sh
Slide 9: EGFR and Target A Multi-Target Inhibitor Program
8 Curis, Inc. EGFR and Target A Multi-Target Inhibitor Program EGFR signaling can lead to tumor growth and development via multiple processes, including enhanced cellular proliferation, survival, and metastasis Many inhibitors of the EGFR have been developed, targeting either the extracellular recep
Slide 10: Curis Multi-Target Inhibitors Are More Potent Than Prototype Drugs in In Vitro Assays
9 Curis, Inc. Curis Multi-Target Inhibitors Are More Potent Than Prototype Drugs in In Vitro Assays Target A Enzyme Assay • 5-10 fold more potent EGFR Enzyme Assay • 15-20 fold more potent EGFR Enzyme Assay Target A Enzyme Assay A
Slide 11: Curis MTIs Display Dose-Dependent Inhibition of Both Targets in A431 cells
10 Curis, Inc. Curis MTIs Display Dose-Dependent Inhibition of Both Targets in A431 cells EGF Control EGFR p-EGFR EGFR p-EGFR 1h 24h EGFRi (uM) CUR-MTI-1 - + - + - + - + - + 0.1 5h Target A readout Loading control Control Target A readout Loading control CUR-MTI-1 1h Control Target Ai CUR-MTI-1 (uM)
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Slide 13: Cur-MTI-1 Improves Anti-Proliferative Activity Against Pancreatic Cancer Cell Lines
12 Curis, Inc. Cur-MTI-1 Improves Anti-Proliferative Activity Against Pancreatic Cancer Cell Lines (IC 50 in uM) Pancreatic tumor cells are not sensitive to EGFR inhibition; Cur-MTI-1 IC values range from 0.27-0.95 uM against 6 major pancreatic carcinoma cell lines Cur-MTI-1 is more potent than a co
Slide 14: Cur-MTI-1 Improves Anti-Proliferative Activity Against Other Major Cancer Cell Lines
13 Curis, Inc. Cur-MTI-1 Improves Anti-Proliferative Activity Against Other Major Cancer Cell Lines (IC 50 in uM) Cell lines from five major types of cancer (lung, breast, prostate, colon, and pancreas) responded better than a combination of EGFRi and Target Ai Cur-MTI-1 highly active against breast
Slide 15: Cur-MTI-1 Displays Potent Induction of Apoptosis In Cancer Cell Lines
14 Curis, Inc. Cur-MTI-1 Displays Potent Induction of Apoptosis In Cancer Cell Lines Cur-MTI-11 induces ~4 to 11x more cell apoptosis as measured by increased caspase 3 & 7 activity EGFRi prototype drug is inactive at a concentration <20 M HCT-116 (Colon): 24 hrs 4X Cur-MTI-1 (0.17 uM) Target Ai (2.
Slide 16: CUR-MTI-1 Is Efficacious in A431 Epidermoid Tumor Xenograft Model
15 Curis, Inc. CUR-MTI-1 Is Efficacious in A431 Epidermoid Tumor Xenograft Model Pre-treatment tumor size is 156+57 mm ³ Days of Treatment 48 mg/kg 24 mg/kg 12 mg/kg 6 mg/kg Vehicle Days of Treatment 48 mg/kg 24 mg/kg 12 mg/kg 6 mg/kg Vehicle
Slide 17: CUR-MTI-1 Is Efficacious in H292 NSCLC Xenograft Model
16 Curis, Inc. CUR-MTI-1 Is Efficacious in H292 NSCLC Xenograft Model Pre-treatment tumor size is 116.3+23.2 mm 3. Animals were treated with compound (15, 30 or 60 mg/kg) or vehicle once daily on days indicated by Days Vehicle 15 mg/kg 30 mg/kg 60 mg/kg Days Vehicle 15 mg/kg 30 mg/kg 60 mg/kg
Slide 18: Comparison of Anti-Tumor Activity of CUR-MTI-1 and Prototype EGFRi in H358 NSCLC Xenograft Model
17 Curis, Inc. Comparison of Anti-Tumor Activity of CUR-MTI-1 and Prototype EGFRi in H358 NSCLC Xenograft Model Animals were treated for once daily for 14 days with erlotinib (100 mg/kg qd) or vehicle control (Cancer Res 65: 9457, 2005) Day Vehicle 15 mg/kg 30 mg/kg 60 mg/kg Pre-treatment tumor size
Slide 19: CUR-MTI-1 Inhibits EGFR Target Activity in a Model of NSCLC by 3 Day Treatment
18 Curis, Inc. CUR-MTI-1 Inhibits EGFR Target Activity in a Model of NSCLC by 3 Day Treatment Vehicle Control CUR-MTI-1
Slide 20: CUR-MTI-1 Induces Apoptosis in a Model of NSCLC by 3 Day Treatment
19 Curis, Inc. CUR-MTI-1 Induces Apoptosis in a Model of NSCLC by 3 Day Treatment Vehicle Control CUR-MTI-1 area of cell death
Slide 21: CUR-MTI-1 Reduces Tumor Cell Proliferation in a Model of NSCLC by Day 3
20 Curis, Inc. CUR-MTI-1 Reduces Tumor Cell Proliferation in a Model of NSCLC by Day 3 CUR-MTI-1 Vehicle Control
Slide 22: Summary of Additional Data Available Under Confidentiality
21 Curis, Inc. Summary of Additional Data Available Under Confidentiality In vitro Metabolism in hepatocytes of different species Receptor, enzyme, kinase panel profiling In vivo PK in three species Dose dependent PD, PK-PD relationship, downstream effector biomarkers, etc. Preliminary PD/efficacy i
Slide 23: Curis EGFR/Target Program Intellectual Property Strategy
22 Curis, Inc. Curis EGFR/Target Program Intellectual Property Strategy Omnibus application (generically claims A+B compounds; in this case, B is EGFR) Claims single compounds having at least two pharmacophores covalently bound via a linker moiety where each pharmacophore binds to a separate therape
Slide 24: Program Summary
23 Curis, Inc. Program Summary Drug Design: Both targets clinically validated In Vitro Assays: Potent small molecules against both targets 2 to 20x more potent in antiproliferation & apoptosis assays compared to a combination of EGFRi/Target Ai prototype compounds Broad activity against wide range o