Slide 1: Corporate Overview December 2016
Corporate Overview December 2016 Exhibit 99.1
Slide 2: Forward-looking statements
This presentation contains certain forward-looking statements about Curis, Inc. (“we,” “us,” or the “Company”) that are intended to be covered by the safe harbor for “forward-looking statements” provided by the Private Securities Litigation Reform Act of 1995, as amended. Words such as “expect(s),”
Slide 3: Mission: Innovative Medicines to Treat Cancer Effectively
Mission: Innovative Medicines to Treat Cancer Effectively Precision Oncology Oncology-Focused Biotech Publicly traded (NASDAQ: CRIS) based in Lexington, MA 62 full-time employees, expertise in clinical development and translational research Pipeline of differentiated small molecule cancer drug candi
Slide 4: Pipeline program overview
Program Indication Stage of Development Preclinical Phase 1 Phase 2 Phase 3 Marketed CUDC-907 HDAC / PI3K MYC-Altered DLBCL MYC-Driven Solid Tumors CA-170 * PD-L1 / VISTA Solid Tumors & Lymphomas CA-327 * PD-L1 / TIM3 Cancers CA-4948 * IRAK4 Hematologic malignancies Erivedge® ** Smoothened Advanced
Slide 5: Curis Immuno-oncology
Curis Immuno-oncology Small molecule design to target interactions between B7 Ig family Majority of inhibitory immune checkpoint proteins belong to this subfamily Shared common folding structure in the extracellular domain Sufficient sites for design and docking of small molecules Multi-year, exclus
Slide 6: Advantages of Small Molecule Drugs
Advantages of Small Molecule Drugs Drug Concentration Required Activity Level Required Activity Level Days Drug Concentration Days Small molecule PK profile Usually less than 24 hour half-life (T1/2) permits flexibility with optimizing dose AND dosing schedule – daily or intermittent dosing Adjust t
Slide 7: Generation of Small Molecule Checkpoint Antagonists
Generation of Small Molecule Checkpoint Antagonists Small molecule design based on structure of interaction hotspots in extracellular domains Small molecule library Functional screening to identify compounds capable of selectively rescuing T cell proliferation and activation in the presence of inhib
Slide 8: CA-170 is a first-in-class oral small molecule immune checkpoint inhibitor
CA-170 is a first-in-class oral small molecule immune checkpoint inhibitor In Phase 1 clinical development CA-170 Oral, small molecule checkpoint inhibitor – PDL1 and VISTA Program Indication Stage of Development Preclinical Phase 1 Phase 2 Phase 3 Marketed CA-170 * PD-L1 / VISTA Solid Tumors & Lymp
Slide 9: CA-170 is a Checkpoint inhibitor Ex-Vivo
CA-170 is a Checkpoint inhibitor Ex-Vivo Activation of human T cells in culture Dose dependent activation of PD-L1 or VISTA-inhibited T cells ex-vivo PD-L1 Rescue (%) IFN-g production used as a marker for T cell activation CA-170 Concentration (log nM) VISTA No activation of CTLA4-inhibited T cells
Slide 10: CA-170 is an Oral Checkpoint Inhibitor In Vivo
CA-170 is an Oral Checkpoint Inhibitor In Vivo B16/F1 syngeneic mouse melanoma model Increased T cell number and activation in tumor-bearing animals with oral CA-170 administration Increased number of activated CD8+ and CD4+ T cells in peripheral circulation Increased percentage of activated (CD69+
Slide 11: CA-170 Anti-Tumor Activity In Vivo
CA-170 Anti-Tumor Activity In Vivo Syngeneic mouse tumor models sensitive to anti-PD1 antibodies CT26 Colon Carcinoma Model B16/F10 Melanoma Model MC38 Colon Carcinoma Model * ** *** * * * * In vivo activity in tumor models grown in immuno-competent C57BL/6 mouse strain CT26 and MC-38 CRC tumors gro
Slide 12: CA-170 Phase 1 Trial
CA-170 Phase 1 Trial Dose escalation stage enrolling in multiple centers in U.S. Open-label, dose escalation and dose expansion trial Up to 300 patients with advanced solid tumors or lymphoma 6 centers in US enrolling patients for dose escalation stage Currently in 3+3 stage of dose escalation Objec
Slide 13: CA-170 Oral Exposure in Patients
CA-170 Oral Exposure in Patients Initial four dose cohorts – continuous once daily dosing PK profile in patients is similar to PK observed in non-clinical models Cmax and AUC at 50mg starting dose in patients is similar to 10mg/kg dose in mouse (active dose in mouse) Dose proportional increase in ex
Slide 14: CA-170 is a Checkpoint Inhibitor in Patients
CA-170 is a Checkpoint Inhibitor in Patients Increased proportion of activated T cells in circulation Increase in percentage of circulating T cells with activation markers Within 24 hours after CA-170 dosing CD69 is one of the earliest induced marker upon T cell activation CD134 (OX40) is a co-stimu
Slide 15: CA-170 Development Plan
CA-170 Development Plan Objective: registration in subpopulations of cancer patients Ongoing Phase 1 Trial Objectives Confirm safety, tolerability and PK/PD relationship with increasing doses of CA-170 Proof-of-concept: Demonstrate objective response with small molecule checkpoint inhibitor Identify
Slide 16: CA-170 Summary
CA-170 Summary Potent and selective, oral small molecule immune checkpoint inhibitor ex-vivo Targets PDL1 and VISTA immune checkpoints Activates isolated T cells that are inhibited by PDL1 or VISTA in culture Potent immune checkpoint inhibitor in vivo in mouse tumor models with oral dosing Biologica
Slide 17: CA-327 is an oral, small molecule immune checkpoint inhibitor
CA-327 is an oral, small molecule immune checkpoint inhibitor Expected to enter clinical development in 2017 CA-327 Oral, small molecule checkpoint inhibitor – PDL1 and TIM3 Program Indication Stage of Development Preclinical Phase 1 Phase 2 Phase 3 Marketed CA-327 * PD-L1 / TIM3 Cancers
Slide 18: CA-327 is a Checkpoint Inhibitor Ex-Vivo
CA-327 is a Checkpoint Inhibitor Ex-Vivo Activation of human T cells in culture Activation of PD-L1 or VISTA-inhibited T cells ex-vivo No activation of CTLA4-inhibited T cells No activation of VISTA-inhibited T cells Potent and selective rescue of human T cell activation ex-vivo (proliferation or IF
Slide 19: CA-327 is a Checkpoint Inhibitor In Vivo
CA-327 is a Checkpoint Inhibitor In Vivo CT-26 syngeneic colorectal cancer mouse model Increased T cell activation in tumor-bearing animals with oral CA-170 administration Increased percentage of activated (CD69+ marker) CD8+ and CD4+ T cells in circulation and in tumors ↑ Percent Active – Tumor Inf
Slide 20: CA-327 Anti-tumor Activity In Vivo
CA-327 Anti-tumor Activity In Vivo Syngeneic mouse tumor models In vivo Tumor Growth Inhibition (TGI) in immuno-competent mouse strains CT26 and MC-38 colorectal cancer, B16/F1 and B16/F10 melanoma models grown subcutaneously and change in tumor size measured 5% TGI Anti-PD1 18% TGI Anti-TIM3 52% TG
Slide 21: CA-327 Summary
CA-327 Summary Potent and selective, oral small molecule immune checkpoint inhibitor ex-vivo Targets PDL1 and TIM3 immune checkpoints Activates isolated T cells that are inhibited by PDL1 or TIM3 in culture Potent immune checkpoint inhibitor in vivo in mouse tumor models with oral dosing Biologicall
Slide 22: CUDC-907 has the potential to become a treatment for MYC-altered cancers
CUDC-907 has the potential to become a treatment for MYC-altered cancers CUDC-907 Phase 2 drug candidate to treat MYC-driven cancers Program Indication Stage of Development Preclinical Phase 1 Phase 2 Phase 3 Marketed CUDC-907 HDAC / PI3K MYC-Altered DLBCL MYC-Driven Solid Tumors
Slide 23: CUDC-907 HDAC and PI3K inhibitor
HDACi PI3Ki CUDC-907 Oral, small molecule inhibitor of HDAC & PI3K enzymes Down-regulates MYC mRNA and protein levels Phase 1 heme study completed (88 patients) – relapsed/ refractory (R/R) lymphoma or multiple myeloma Objective responses (multiple CR and PR) in certain patients with R/R DLBCL, incl
Slide 24: CUDC-907 Phase 1 Trial Completed
CUDC-907 Phase 1 Trial Completed Study Population Patients with relapsed/refractory lymphoma or multiple myeloma after ≥ 2 prior regimens 76 patients treated with monotherapy: 41 in dose escalation, 35 in dose expansion stage 12 patients treated with combination of CUDC-907 + rituximab Treatment Dos
Slide 25: Phase 1 Safety Profile
Phase 1 Safety Profile Most Common AEs CUDC-907 Phase 1 Monotherapy Data at RP2D Incidence ( % ) Grade 1, 2 Grade 3 Grade 4 Diarrhea 55 4 0 Fatigue 28 6 0 Nausea 31 0 0 Vomiting 16 0 0 Thrombocytopenia 0 21 4 Neutropenia 0 4 0 Hyperglycemia 0 0 0 Colitis 0 0 0 No DLTs at RP2D Safety Diarrhea, fatigu
Slide 26: CUDC-907 Phase 1 Efficacy
CUDC-907 Phase 1 Efficacy Monotherapy responses correlated with MYC alterations in DLBCL Data as of March 15, 2016 -- presented at 2016 EHA 18 of 25 R/R DLBCL patients treated with monotherapy were evaluable for assessment (2 CR, 6 PR, 4 SD) MYC status assessed by FISH or IHC MAXIMUM CHANGE IN TUMOR
Slide 27: CUDC-907 Phase 2 Trial
CUDC-907 Phase 2 Trial Monotherapy in MYC-altered relapsed/refractory DLBCL Open label study to evaluate the efficacy and safety of CUDC-907 monotherapy in patients with relapsed/refractory (R/R) DLBCL – after 2 prior treatments Analysis of primary (ORR) and secondary (PFS, OS, DoR & safety) endpoin
Slide 28: CUDC-907 DLBCL Development Plan
CUDC-907 DLBCL Development Plan Objective: registration for treatment of MYC-altered DLBCL Ongoing Phase 2 monotherapy trial Treatment of patients with MYC-altered R/R DLBCL with 2 prior treatments Based on results, expect to discuss with FDA in 2017 potential for accelerated registration path Plann
Slide 29: DLBCL and MYC
DLBCL and MYC 72,580 estimated new cases of Non-Hodgkin Lymphoma in the US in 2016 (NCI’s SEER database) 30-35% of NHL cases are DLBCL Approximately 35% of newly diagnosed DLBCL have MYC alterations Double-hit lymphoma (DHL) – rearrangements of MYC and BCL2 and/or BCL6 genes – by FISH Single-hit lym
Slide 30: MYC-Altered DLBCL
MYC-Altered DLBCL DLBCL with MYC alterations Poor prognosis using current treatment regimens No clear consensus on optimal treatment1 Worse prognosis with concurrent alterations in BCL2 or BCL6 Significant unmet need population: ~ 1/3 of all DLBCL MYC gene rearrangements (by FISH) – up to 14% of cas
Slide 31: Immuno-oncology and Precision Oncology
Immuno-oncology and Precision Oncology Orally available small molecules * Licensed from Aurigene **Developed and marketed by Genentech (Curis receives royalty income) Program Indication Stage of Development Preclinical Phase 1 Phase 2 Phase 3 Marketed CUDC-907 HDAC / PI3K MYC-Altered DLBCL MYC-Drive
Slide 32: Summary of Financial Data
$53.4MCash & Marketable Securities $20.9MErivedge® secured debt (non-recourse to Curis) 140.0MShares Outstanding - Basic 155.5MShares Outstanding - Fully Diluted* *Diluted Shares= 140.0M basic shares + 15.5M options Summary of Financial Data As of September 30, 2016
Slide 33: Projected Milestones
CA-170 Phase 1 Dose Escalationn Ongoing Phase 1 Expansionn Begin Enrollment in 1H 2017 CA-327 INDn Mid-2017 filing CUDC-907 Phase 2 in DLBCLn Initial Results in 1H 2017 Phase 1 in Solid Tumorsn Initial Results in 2H 2017 CA-4948 INDn Mid-2017 filing Projected Milestones
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