Docstoc
EXCLUSIVE OFFER FOR DOCSTOC USERS
Try the all-new QuickBooks Online for FREE.  No credit card required.

Corporate Overview

Document Sample
Corporate Overview Powered By Docstoc
					Corporate Overview
May 3, 2011



NASDAQ: CRIS
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 from those indicated
by these forward-looking statements as a result of various important factors, including risks relating
to: both our and our collaborators’ ability to successfully research, obtain regulatory approvals for,
develop and commercialize products based upon our technologies; our ability to obtain and
maintain proprietary protection for our technologies and product candidates, including our multi-
target inhibitors; competitive pressures; our ability to maintain strategic collaborations, including
with Genentech and Debiopharm; our ability to successfully execute on, and receive favorable
results from, our proprietary drug development efforts; our ability to raise additional funds to finance
our operations; and those factors described in our Quarterly Report on Form 10-Q for the quarter
ended March 31, 2011, and other reports that we file with SEC.


The forward-looking statements included in this presentation represent our views as of the date of
this presentation. We anticipate that subsequent events and developments will cause our views to
change. While we may elect to update these forward-looking statements in the future, we
specifically disclaim any obligation to do so. These forward-looking statements should not be relied
upon as representing our views as of any date subsequent to the date of this presentation.

                                                                                                           2
Curis Pipeline: Balanced Business Model

                                                                       Preclinical
             Discovery                                 Research        Development IND              I      II    III    NDA Products

                                         Phase I expansion Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)cohort
   Cancer
  Advanced basal cell carcinoma           Preclinical
                                        Pivotal Phase completed II (1)
  Phase II*
                                                        Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)
   Cancer
  Operable basal cell carcinoma           Preclinical Phase II

                                                          Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)
   Cancer
  NCI and investigator-sponsored trials    Preclinical I / II (2)
                                               Phase

  CUDC-101 (EGFR/Her2/HDAC Inhibitor)
   Cancer
  H&N, NSCL, breast, gastric, liver cancers                           Preclinical
                                                                                Phase Ib
                                                                                   Phase II*
  Debio 0932 (Hsp90 Inhibitor)
  Cancer                                                             Preclinical
                                                                     Preclinical Phase I
   Cancer
  Multiple cancers
                                                                                   Phase II*
  CUDC-907 (Pi3K / HDAC Inhibitor)
   Cancer
  Phase II* cancers
  Multiple                                            PreclinicalPreclinical

  Network Targeted Inhibitor Pipeline
   Cancer
  Multiple cancers                    PreclinicalPreclinical
                                                                                       Phase II*
(1) Positive outcome reported in pivotal trial; Genentech and Roche have indicated that they anticipate filing U.S. NDA submission in 2011.
(2) NCI and investigator sponsored trials include studies being conducted by the NCI and other third-parties under collaborative relationships with
Genentech for indications including medulloblastoma, glioblastoma and pancreatic, small cell lung, stomach, gastroesophageal junction and breast cancers.

                                                                                                                                                            3
Key 2011 Milestones

• Vismodegib (Hedgehog Pathway Inhibitor in Collaboration with Genentech/Roche)
     ─   Positive outcome in pivotal Phase II advanced basal cell carcinoma study reported first quarter of
         2011
          ▪   Full data to be presented at the European Association of Dermato-Oncology June 20-23, 2011
          ▪   U.S. NDA submission expected in 2011
          ▪   European NDA submission timing pending Roche planned discussions with EMA
     ─   Ongoing Phase II operable BCC study
     ─   Potential data from ongoing Phase I and II studies under NCI-Genentech collaboration

• CUDC-101 (EGFR, Her2, HDAC inhibitor)
     ─   Complete enrollment in Phase Ib expansion trial
     ─   Initiate Phase I study in HPV(-) advanced head and neck cancer patients in combination with
         cisplatin and radiation in 1H 2011
     ─   Phase I initiation for oral formulation of CUDC-101 in late 2011
     ─   Exploring potential Phase II clinical study in advanced liver cancer


• Debio 0932 (Hsp90 inhibitor licensed to Debiopharm)
     ─   Debiopharm continue ongoing Phase I study with encouraging safety and activity profile
         observed to-date

• CUDC-907 (Pi3K, HDAC inhibitor)
     ─   Complete IND-enabling studies and submit IND application by end of 2011


                                                                                                              4
Curis Pipeline: Balanced Business Model

                                                                       Preclinical
             Discovery                                 Research        Development IND              I      II    III    NDA Products

                                         Phase I expansion Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)cohort
   Cancer
  Advanced basal cell carcinoma           Preclinical
                                        Pivotal Phase completed II (1)
  Phase II*
                                                        Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)
   Cancer
  Operable basal cell carcinoma           Preclinical Phase II

                                                          Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)
   Cancer
  NCI and investigator-sponsored trials    Preclinical I / II (2)
                                               Phase

  CUDC-101 (EGFR/Her2/HDAC Inhibitor)
   Cancer
  H&N, NSCL, breast, gastric, liver cancers                           Preclinical
                                                                                Phase Ib
                                                                                   Phase II*
  Debio 0932 (Hsp90 Inhibitor)
  Cancer                                                             Preclinical
                                                                     Preclinical Phase I
   Cancer
  Multiple cancers
                                                                                   Phase II*
  CUDC-907 (Pi3K / HDAC Inhibitor)
   Cancer
  Phase II* cancers
  Multiple                                            PreclinicalPreclinical

  Network Targeted Inhibitor Pipeline
   Cancer
  Multiple cancers                    PreclinicalPreclinical
                                                                                       Phase II*
(1) Positive outcome reported in pivotal trial; Genentech and Roche have indicated that they anticipate filing U.S. NDA submission in 2011.
(2) NCI and investigator sponsored trials include studies being conducted by the NCI and other third-parties under collaborative relationships with
Genentech for indications including medulloblastoma, glioblastoma and pancreatic, small cell lung, stomach, gastroesophageal junction and breast cancers.

                                                                                                                                                            5
Hedgehog-Associated Cancers


 Mutation Driven          Ligand Driven
 Basal Cell Carcinoma
                          Small Cell Lung Cancer
 Medulloblastoma
                          Breast Cancer
 Rhabdomyosarcoma
                          Colorectal Cancer
                          Esophageal Cancer
                          Liver Cancer
                          Ovarian Cancer
                          Pancreatic Carcinoma
                          Prostate Cancer
                          Stomach Cancer

                                                   6
Vismodegib Demonstrated Clinical Benefit in BCC
Patients in Phase I Clinical Trial

          Best Response                                            Patients, N=33
          Complete Response                                                2 (6.1%)
          Partial Response                                                17 (51.5%)
          Stable Disease                                                     11
          Disease Progression                                                 4


          Imaging                                                             8*
          Clinical Examination                                               10
          Duration of Response (median)                                  12.8+ months

  • Duration of response as of January 26, 2010. The range of response was 3.7 – 26.4 months and
      ongoing
  •   Responses confirmed by Independent Review Facility; measured using RECIST criteria
  •   Genentech and Roche are responsible for the clinical development and commercialization of GDC-0449

LoRusso, Rudin, Reddy, et al., Clinical Cancer Research, February 2011
                                                                                                           7
Phase I Study of Vismodegib 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   8
Phase I Study of Vismodegib 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
                                                                                              9
Phase I Study of Vismodegib in Locally Advanced,
Multifocal or Metastatic BCC




                                              After 1 month




          Baseline                                                          After 2 months
                       49 year old with multiple large, invasive lesions of skin
Presented at American Association for Cancer Research Annual Meeting 2008
                                                                                             10
Phase I Study of Vismodegib 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
Vismodegib Phase I Clinical Trial
BCC Patient Safety Summary

• No dose-limiting toxicities observed
• No grade 5 toxicities; 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 muscles spasms, atrial fibrillation, aspiration, back pain,
       corneal abrasian, dehydration, keratitis, lymphopenia, pneumonia, urinary
       tract infection, a prolonged QT interval, increased serum alkaline
       phosphatase and increased serum potassium
• Grade 1 and 2 observed adverse events included muscle spasms,
   dysguesia (altered taste sensation), anorexia, weight decrease,
   hypocalcemia and dyspepsia
• Safety data is similar to that observed in broader Phase I clinical trial

Von Hoff, et al., New England Journal of Medicine, September 2009
                                                                                    12
Vismodegib Phase II Clinical Trial Status



    Patient           Advanced Basal Cell         Operable Nodular Basal         NCI and Investigator
    Population            Carcinoma                  Cell Carcinoma              Sponsored Trials (1)

    Phase                Pivotal Phase II                 Phase II                       Phase I/II
    # Patients                N = 100                      N = 50                       multiple trials


    Design         Single ARM: GDC-0449         Single ARM: GDC-0449          Various



    Mechanism      Targeting mutation in a      Targeting mutation in a       Targeting paracrine, residual
                   component of the Hedgehog    component of the Hedgehog     cancer cells and mutation
                   pathway                      pathway                       mechanisms
    Primary        Overall response rate        Complete clearance of BCC
    Endpoint                                    lesion
    Status         • Completed 1Q 2011          • FPI treated October 2010    • Awaiting results from
                   • Primary endpoint met                                       ongoing studies
                   • U.S. NDA submission
                     planned 2011


(1) – NCI and investigator sponsored trials include studies being conducted by the NCI and other third-
parties under collaborative relationships with Genentech for indications including medulloblastoma,
glioblastoma and pancreatic, small cell lung, stomach, gastroesophageal junction and breast cancers,
among others.
                                                                                                              13
Curis Pipeline: Balanced Business Model

                                                                       Preclinical
             Discovery                                 Research        Development IND              I      II    III    NDA Products

                                         Phase I expansion Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)cohort
   Cancer
  Advanced basal cell carcinoma           Preclinical
                                        Pivotal Phase completed II (1)
  Phase II*
                                                        Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)
   Cancer
  Operable basal cell carcinoma           Preclinical Phase II

                                                          Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)
   Cancer
  NCI and investigator-sponsored trials    Preclinical I / II (2)
                                               Phase

  CUDC-101 (EGFR/Her2/HDAC Inhibitor)
   Cancer
  H&N, NSCL, breast, gastric, liver cancers                           Preclinical
                                                                                Phase Ib
                                                                                   Phase II*
  Debio 0932 (Hsp90 Inhibitor)
  Cancer                                                             Preclinical
                                                                     Preclinical Phase I
   Cancer
  Multiple cancers
                                                                                   Phase II*
  CUDC-907 (Pi3K / HDAC Inhibitor)
   Cancer
  Phase II* cancers
  Multiple                                            PreclinicalPreclinical

  Network Targeted Inhibitor Pipeline
   Cancer
  Multiple cancers                    PreclinicalPreclinical
                                                                                       Phase II*
(1) Positive outcome reported in pivotal trial; Genentech and Roche have indicated that they anticipate filing U.S. NDA submission in 2011.
(2) NCI and investigator sponsored trials include studies being conducted by the NCI and other third-parties under collaborative relationships with
Genentech for indications including medulloblastoma, glioblastoma and pancreatic, small cell lung, stomach, gastroesophageal junction and breast cancers.

                                                                                                                                                        14
Current Trend in Oncology Targeted Therapy

• Limitations of targeted single point (pathway node)
 re: tolerance and resistance mechanisms
• Systems/network disruption is increasingly
 accepted as future approach for treatment regimens
• Underlying molecular profile(s) are emerging
 providing greater insight into particular aberrations
• Translational medicine coupling biomarkers with
 targeted therapies is becoming established
 protocol



                                                         15
CUDC-101 and Other Curis Network-Targeted
Inhibitors

• Curis may be ideally positioned with rational drug
 design approach: Network-targeted Inhibitor
  ─ Network disruption via highly selective, multi-target
    approach (kinase and HDAC inhibition)
  ─ HDAC component modulates cellular signaling at
    multiple levels:
     ▪ modulate chromatin structure and transcription factors to
       influence gene expression
     ▪ HDACs modulate non-histone proteins, and effect protein
       function e.g., tubulin, HSP90, PP-1 etc.
   ─ CUDC-101 and other pipeline molecules may
     address multiple resistance mechanisms

                                                                   16
Single-Target Drugs: 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
 Signaling         Signaling    Signaling                Signaling     Signaling               Signaling




   Transcription                   Transcription                         Transcription




                                                                                                      17
CUDC-101 Mechanism: Cancer Network Disruption
    Limited Pathway Inhibition by                   Improved Blockade of
      Traditional Targeted Agent
Erlotinib                                      Signaling Pathways by CUDC-101
                                                                       CUDC-101
               EGFR-L858R                      EGFR   HER2/HER3   MET
               EGFR-L858R




                                                                                    CUDC-101
EGFR/HER2
EGFR/HER2                                                                     EGFR/HER2
 Inhibitor                                                                     Inhibition
                Akt              MAPK        Akt                   MAPK
                Akt
             Signaling          Signaling Signaling               Signaling
             Signaling


                                                                                    CUDC-101
                                                                              Class II HDAC
                                                                                Inhibition




              Transcription                 Transcription
              Transcription
                                                                                    CUDC-101

                                                                              Class I HDAC
                                                                                Inhibition
                                              Tumor Suppressor Genes
                                                                                               18
CUDC-101 Structure Design

Integrates a hydroxamic acid HDAC-inhibiting moiety into a quinazoline receptor
tyrosine kinase inhibition pharmacophore
               HDAC Inhibitors                                  EGF/Her2 Inhibitors

                           O                                                        H N                 CH
                                   O                     H3C
                  N                                                     O                 N
SAHA                           N                                O
                                                                                                                   erlotinib
                                                         H3C O
                      O
MW 264.3                                                                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




JNJ-16241199                                                                                                       gefitinib
MW 413.45                                                                                                          MW 446.9




                           HDAC/ EGF/Her2 Inhibitors
                                                                        HN
                                        H                                                     CH
                                        N                       O
                                   HO                                           N
                                            O            H 3C
                                                                                                        CUDC-101
                                                                O           N
                                                                                                        MW 434.5
                                                                                                                               19
CUDC-101: 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 potent than erlotinib
 • Her2 inhibition: 5-10 fold more potent than erlotinib and similar to lapatinib
 Selectivity
 • 72 kinases assayed
 • CUDC-101 appears to be a weak inhibitor of VEGFR2, Lck, Lyn, Abl-1, FGFR2,
   Flt3 and Ret kinases (IC50 values are within the range of 1-5 mM)
 • At 10 mM concentration, <50% inhibition of other kinases
                                                                                    20
CUDC-101, A Single Small Molecule with Multi-Targeted
Activities to Disrupt Signaling Network
                        EGFR   HER2/HER3   MET         EGFR     Ctrl   101 Tarceva
  Receptors

                                                                                 pEGFR
                                                       HER-2
                                                                                 EGFR
                                                       HER-3
                                                                                 pHER2
                                                        MET                      HER2
                                                                                 pHER3
Molecules
Signaling




                     Akt                    MAPK                                 HER3
                  Signaling                Signaling    Akt
                                                                                 pMET

                                                       MAPK                      MET
                                                                                 pAkt
                                                                                 Akt
  Transcription




                                                        ER
                                                                                 pMAPK
                    Transcription                      Ac-p53                    MAPK
                                                       Ac-H3                     p21

                                                        p21                      Tubulin
                      Tumor Suppressor Genes                                               21
CUDC-101 Directly Inhibits HDAC, EGFR and HER2 in Xenografts
Resulting in Increased Apoptosis and Cell Cycle Arrest

                  p-EGFR              p-HER2              Ki-67       Caspase 3
      Control
      CUDC-101




                                                                    Vehicle     60 mg/kg
                 Vehicle   15         30       60 mg/kg
                                                            Ac-H3
  Ac-H3                                                    p-EGFR
 GAPDH                                                     GAPDH

                           HCC-827 cell line                           H292 cell line      22
CUDC-101 Clinical Phase I(a) Trial Summary

 Status        ─ Phase II Dose escalation study completed Q2 2010
               ─ Phase Dose escalation study completed Q2 2010  Completed
Progress           ▪ 25 patients enrolled
                   ▪ 25 patients enrolled
                   ▪ PK dose proportional
                   ▪ PK dose proportional                           Well Tolerated
                        75 mg/ m 2           150 mg/ m2
                   ▪ MTD @ 275 mg/m2
                   ▪ MTD @ 275 mg/m2
                   ▪ Therapeutic window = 150mg/m2 – 275mg/m2
                   ▪ Therapeutic window = 150mg/m2 – 275mg/m2
                    High Exposure
                   ▪ Final study data presented at EORTC-NCI-AACR Symposium on
                   ▪ Final study data presented at EORTC-NCI-AACR Symposium on
                      Molecular Targets and Cancer Therapeutics in November 2010
                      Molecular Targets and Cancer Therapeutics in November 2010

Favorable PK         Longer T1/2
 Biological    ─ Confirmed partial response in a gastric cancer patient
               ─ Confirmed partial response in a gastric cancer patient
                    than SAHA
 Activity
                  ▪ Gastric cancer patient, dosed at 275 mg/m2; 14 weeks, 7 cycles;
                  ▪ Gastric cancer patient, dosed at 275 mg/m2; 14 weeks, 7 cycles;
                    ~55% reduction in target lesion
                    ~55% reduction in target lesion
               ─ >20%Dose
               ─ >20% regression
                        regression
                  Proportionality
                  ▪ Head and neck cancer patient, dosed at 275 mg/m2; 2 cycles of
                  ▪ Head and neck cancer patient, dosed at 275 mg/m2; 2 cycles of
                    treatment
                    treatment
               ─ Mixed response; reduction in the size of 1 target lesion
               ─ Mixed response; reduction in the size of 1 target lesion
Biomarkers                             HER2 Protein
                   ▪ Head and neck cancer patient, dosed at 150 mg/m2
                   ▪ Head and neck cancer patient, dosed at 150 mg/m2
               ─ Stable disease (> 3 months)
               ─ Stable disease (> 3 months)
                   ▪ Breast cancer patient, dosed at 150 mg/m2
                   ▪ Breast cancer patient, dosed at 150 mg/m2
                                     Partial Response
                                                                                      23
CUDC-101 Clinical Phase I(a) Trial Summary

 Status        ─ Dose-limiting toxicity of transient grade 2 elevated Creatinine
               ─ Dose-limiting toxicity of transient grade 2 elevated Creatinine
                                                                    Completed
Progress         levels observed at 300 mg/m2
                  levels observed at 300 mg/m2
                                                                   Well Tolerated
               ─ 75 mg/m2,150 mg/m2, 225 mg/m2, and 275mg/m2 appear
               ─ 75 mg/m2,150 mg/m2, 225 mg/m2, and 275mg/m2 appear
                        75 mg/ m 2           150 mg/ m2

                 well-tolerated
                  well-tolerated
                   ▪High Exposure adverse events were mild to moderate and included
                    ▪ Most frequent adverse events were mild to moderate and included
                      Most frequent
                      fatigue, vomiting, dyspnea (shortness of breath), pyrexia (fever),
                      fatigue, vomiting, dyspnea (shortness of breath), pyrexia (fever),
                      and dry skin
                      and dry skin

Favorable PK         Longer T1/2
                      than SAHA


                       Dose
                   Proportionality



Biomarkers                                HER2 Protein



                                      Partial Response
                                                                                           24
CUDC-101 Phase I(a) Observed Biological Activity
Head and Neck Cancer




          Baseline                                       Post 4th Cycle

         Mixed Response in a patient with metastatic salivary gland cancer
         - reduction in mediastinal mass at 150 mg/m2 dose level.

                                                                             25
CUDC-101 Phase I(a) Observed Biological Activity
Head and Neck Cancer



                                         primary lesion
                                             of jaw




                  Baseline                                     End of Cycle 2
A 49-year-old female diagnosed with squamous cell carcinoma of the tongue previously treated
with partial glossectomy, XRT and carboplatin/paclitaxel/5-FU/cetuximab enrolled at 275mg/m2
dose level and achieved an overall decrease in primary lesion of jaw >20% by RECIST after 2
cycles of CUDC-101.
                                                                                               26
CUDC-101 Phase I(a) Observed Biological Activity
Gastric Cancer     abdominal wall
                  metastatic lesion




                                                     Baseline                                 End of Cycle 4
                                   300
                                                                                    A 65 years old male with recurrent gastric
                                                                                    cancer previously treated with
      Alkaline Phosphatase (U/L)




                                   250
                                                                                    chemotherapy irradiation with
                                   200
                                                                                    oxaliplatin/5-FU with measurable
                                                                                    abdominal wall metastasis at baseline
                                   150
                                                                                    had confirmed partial response
                                                                                    by RECIST with 56% reduction in target
                                   100
                                                                                    lesion following 4 cycles of CUDC-101 at
                                         0   20      40         60       80   100   275 mg/m2 level .
                                                  Time On Study (Days)                                                           27
CUDC-101 Phase Ib Study

• Phase Ib expansion study initiated August 2010
    ─ 50-patients with breast, gastric, head & neck, liver and NSCL cancers to be
      enrolled (10 patients each tumor type)
        ▪ 7 study centers
        ▪ 43 patients enrolled to-date; enrollment complete in all cohorts except
          NSCLC (initiated cohort Q4 2010)
    ─ Primary objective is to compare the safety and tolerability of CUDC-101 at
      one of two dosing regimens
        ▪ Dosing at either 5x/week with one week off or 3x/week for three weeks
          with one week off
    ─ Secondary objectives include
        ▪ Evaluating the efficacy of CUDC-101 in subjects with advanced and
          refractory solid tumors
        ▪ Assessing the pharmacokinetics of CUDC-101 in this patient population
        ▪ Evaluating for pharmacodynamic biomarkers of CUDC-101 activity


                                                                                    28
Initial Observations from CUDC-101 Phase Ib Study

• Patients appear to generally tolerate CUDC-101 at either dose
 regimen
   ─ Toxicities deemed likely attributable to CUDC-101 similar to those
     seen during the Phase I dose escalation clinical trial

• Stable disease observed in a number of patients
   ─ Stable disease has been observed to date in 5 liver cancer patients:
      ▪ 2 liver patients received CUDC-101 on a 3 times per week
        dosing scheduling for over 26 weeks, or greater than 6 months
        with one patient demonstrating a >20% reduction in primary liver
        tumor.
   ─ Stable disease also observed in head and neck cancer as well as
     breast cancer patients




                                                                            29
Potential in Head & Neck Cancer

• About Head & Neck Cancer
   ─ 43,000 cases of head and neck squamous cell carcinoma annually in the
     United States
   ─ Approximately two thirds of these patients present with advanced disease
       ▪ Approximately 60-70% head and neck cancers are HPV-
   ─ Current standard of care is radiation plus chemotherapy (cisplatin)
   ─ It has been reported that overexpression of EGFR results in a significantly
     lower overall survival and disease control
   ─ It has been shown that 80-100% of HNSCC overexpress EGFR
   ─ HER2 is often overexpressed with EGFR in 20-40% of HNSCC tumors and
     has been shown preclinically to confer resistance against standard
     regimens

• Potential competitive advantage with CUDC-101
   ─ EGFR and HER2 core targets
   ─ HDAC inhibitors have been shown to synergize with radiation
   ─ Commercial path for current CUDC-101 formulation as patients receive
     radiation therapy daily for 6-7 weeks

                                                                                   30
CUDC-101 Phase I H&N Study Dosing Scheme

• 8-week treatment course
    ─ 1 week CUDC-101 run-in period
    ─ 7 week combination treatment
• Radiation – Administered daily (5 days/week)
• Cisplatin – Administered on Days 2, 23 and 44
• CUDC-101 – Administered 3x/week (MWF) for 8 consecutive weeks - Initial starting dose
  will be 225 mg/m2.
            Cisplatin                    Cisplatin                            Cisplatin




  Week -1       Week 1   Week 2    Week 3        Week 4     Week 5   Week 6        Week 7

 CUDC-101                          CUDC-101 Administration (MWF)

                                            Radiation therapy




• Subjects will be followed for an additional 12 months to assess toxicities and
  functional changes.
                                                                                            31
Potential in Head & Neck Cancer

• Study Assessments
   ─ Biomarker Assessments:
      ▪ Tumor biopsy pre-treatment and at the end of the CUDC-101
        one week run-in period
          - EGFR, HER2, HDAC status and inhibition
          - HPV Status
      ▪ Circulating Tumor Cells collected pre-treatment and at the end of
        run-in period
   ─ Conventional Imaging (CT/MRI):
      ▪ Pretreatment and 4-8 weeks post treatment and the quarterly
        during follow-up
   ─ Functional Imagining (PET Scan):
      ▪ Pretreatment and 12 weeks post end of treatment


                                                                            32
CUDC-101 Oral Formulation Development

• Preclinical data suggests that CUDC-101 may be orally administered
    ─ Non-GLP toxicity study resulted in adequate safety profile
    ─ Planning formulation work and GLP toxicity

• Clinical Development
    ─   Standard Phase 1 Dose Escalation Study
    ─   Approximately 15-25 pts
    ─   Objective to determine safety and MTD
    ─   Patient population may be targeted to specific cancers if biological activity
        is observed in the ongoing Phase Ib or planned Phase I HNC studies

• Potential Oral formulation Advantages
    ─ Convenience for patients offers flexibility in dose schedule
    ─ Increase the potential indications for CUDC-101 in the oncology setting
    ─ Increased commercial potential is attractive to future partner




                                                                                        33
Potential of CUDC-101 in HCC


• Preclinical data suggested potent activity of CUDC-101 in
 hepatocellular cell lines and xenograft models
• Phase Ib trial study to date has shown that four subjects have
 remained on treatment for at least 4 months (two patients greater
 than 6 months with one on study at 8 months).
    ─ > 20% reduction observed in one target lesion
• PIs encouraged by data and 1 had prioritized their liver patients for
  this trial based on activity seen to date
   ─ Activity demonstrated in sorafinib failures
• Potential studies (either or, planning ongoing);
    ─ Phase II in sorafinib failures (single agent)
    ─ Phase I/II combination with sorafinib
• We believe that this level of activity is very encouraging given the
  extremely poor prognosis of the subjects

                                                                          34
Curis Pipeline: Balanced Business Model

                                                                       Preclinical
             Discovery                                 Research        Development IND              I      II    III    NDA Products

                                         Phase I expansion Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)cohort
   Cancer
  Advanced basal cell carcinoma           Preclinical
                                        Pivotal Phase completed II (1)
  Phase II*
                                                        Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)
   Cancer
  Operable basal cell carcinoma           Preclinical Phase II

                                                          Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)
   Cancer
  NCI and investigator-sponsored trials    Preclinical I / II (2)
                                               Phase

  CUDC-101 (EGFR/Her2/HDAC Inhibitor)
   Cancer
  H&N, NSCL, breast, gastric, liver cancers                           Preclinical
                                                                                Phase Ib
                                                                                   Phase II*
  Debio 0932 (Hsp90 Inhibitor)
  Cancer                                                             Preclinical
                                                                     Preclinical Phase I
   Cancer
  Multiple cancers
                                                                                   Phase II*
  CUDC-907 (Pi3K / HDAC Inhibitor)
   Cancer
  Phase II* cancers
  Multiple                                            PreclinicalPreclinical

  Network Targeted Inhibitor Pipeline
   Cancer
  Multiple cancers                    PreclinicalPreclinical
                                                                                       Phase II*
(1) Positive outcome reported in pivotal trial; Genentech and Roche have indicated that they anticipate filing U.S. NDA submission in 2011.
(2) NCI and investigator sponsored trials include studies being conducted by the NCI and other third-parties under collaborative relationships with
Genentech for indications including medulloblastoma, glioblastoma and pancreatic, small cell lung, stomach, gastroesophageal junction and breast cancers.

                                                                                                                                                        35
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 clinical development and regulatory objectives
       ▪ Early payments provide Curis with adequate capital to fund operations
          well into 2012
    ─ Eligible for royalties on net sales by Debiopharm or its sublicensees
    ─ Debiopharm assumes all development costs and oversight

• First patient enrolled in Phase I clinical trial in April 2010
    ─ $2 million received in Q3 2009 on contract execution
    ─ $8 million cash payment received by Curis in Q1 2010 upon acceptance of
      CTA filing by French authorities
    ─ Additional $3 million payment received in Q3 2010 upon Debiopharm’s
      treatment of the 5th patient in a Phase I clinical trial
    ─ Next payment due upon Debiopharm’s treatment of the 5th patient in a
      Phase II clinical trial
                                                                                 36
Curis Pipeline: Balanced Business Model

                                                                       Preclinical
             Discovery                                 Research        Development IND              I      II    III    NDA Products

                                         Phase I expansion Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)cohort
   Cancer
  Advanced basal cell carcinoma           Preclinical
                                        Pivotal Phase completed II (1)
  Phase II*
                                                        Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)
   Cancer
  Operable basal cell carcinoma           Preclinical Phase II

                                                          Phase II
  Vismodegib (GDC-0449/RG3616) (Hedgehog Pathway Inhibitor)
   Cancer
  NCI and investigator-sponsored trials    Preclinical I / II (2)
                                               Phase

  CUDC-101 (EGFR/Her2/HDAC Inhibitor)
   Cancer
  H&N, NSCL, breast, gastric, liver cancers                           Preclinical
                                                                                Phase Ib
                                                                                   Phase II*
  Debio 0932 (Hsp90 Inhibitor)
  Cancer                                                             Preclinical
                                                                     Preclinical Phase I
   Cancer
  Multiple cancers
                                                                                   Phase II*
  CUDC-907 (Pi3K / HDAC Inhibitor)
   Cancer
  Phase II* cancers
  Multiple                                            PreclinicalPreclinical

  Network Targeted Inhibitor Pipeline
   Cancer
  Multiple cancers                    PreclinicalPreclinical
                                                                                       Phase II*
(1) Positive outcome reported in pivotal trial; Genentech and Roche have indicated that they anticipate filing U.S. NDA submission in 2011.
(2) NCI and investigator sponsored trials include studies being conducted by the NCI and other third-parties under collaborative relationships with
Genentech for indications including medulloblastoma, glioblastoma and pancreatic, small cell lung, stomach, gastroesophageal junction and breast cancers.

                                                                                                                                                        37
HDAC/PI3K Inhibitor May Potentially Overcome
Limitations of RTK, Raf, MEK or PI3K Inhibitors
                                                                             PI3K/HDAC
  RTK inhibitors        Raf/MEK inhibitors         PI3K inhibitors            inhibitors
         RTK     MET             RTK     MET              RTK     MET              RTK     MET




 Ras      PI3K           Ras      PI3K             Ras     PI3K            Ras      PI3K

  Raf            Akt     Raf             Akt       Raf            Akt      Raf             Akt


 MEK             mTor    MEK             mTor      MEK            mTor    MEK              mTor

 ERK                     ERK                       ERK                    ERK




                                                                                 Tumor suppressor

RTK Further Mutation                                                       PI3K-Akt Inhibition
                         PI3K-Akt Activation    Raf-MEK-ERK Activation
    Adaptation          Downstream Mutation                              Raf-MEk-ERK Blockage
                                                 Downstream Mutation
Downstream Mutation                                                      Adaptation Disruption
                                                                                                  38
Corporate




            39
Financial Data


                                                                                March 31, 2011
                                                                                                 (000’s)

Cash, cash equivalents, investments                                                      $      36,500
Liabilities, other than warrant liability                                                $        3,400
Warrant liability                                                                        $        3,100
Shareholders’ equity                                                                     $      40,500
Basic shares outstanding                                                                        76,350
Fully diluted shares outstanding                                                                 89,965 (1)
2010 net loss                                                                            $        4,400
(1) Fully diluted shares outstanding of 89.965 million are comprised of: (i) 76.35 million basic shares
     outstanding, (ii) warrants to purchase 1.60 million shares with an exercise price of $3.55 per
     share, and (iii) options to purchase 12.0 million shares.

                                                                                                           40
Corporate Overview
May 3, 2011



NASDAQ: CRIS

				
DOCUMENT INFO