Jefferies Healthcare Conference. June 2016

Transcription

1 Jefferies Healthcare Conference June 2016

2 Forward Looking Statements This presentation contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of These forward-looking statements include, among others, statements about our business, plans, prospects and strategies. The words anticipates, believes, estimates, expects, intends,, may, plans, projects, would and similar expressions are intended to identify forward-looking statements, although not all forwardlooking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. Important factors that may cause or contribute to such differences include the factors set forth under the caption Risk Factors in our in our most recent Form 10-K and Form 10-Q and the factors that are discussed in other filings that we periodically make with the Securities and Exchange Commission ( 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 except as required by law. 2

3 Development Pipeline Program Indication Stage of Development Preclinical Phase 1 Phase 2 Phase 3 Marketed HDAC / PI3K * PD-L1 / VISTA CA-4948 IRAK4 * MYC-Altered DLBCL MYC-Driven Solid Tumors Solid Tumors Lymphomas Heme Malignancies Focus of this presentation * TBD PD-L1 / TIM3 Cancers Erivedge SMO ** Advanced Basal Cell Carcinoma * Licensed from Aurigene (PD-L1/TIM3 program is subject to Curis licensing from Aurigene) ** Developed and marketed by Genentech (Curis receives royalty income) 3

4 Drug Candidate to Treat MYC-driven Cancers

5 Drug Candidate to Treat MYC-driven Cancers Program Indication Stage of Development Preclinical Phase 1 Phase 2 Phase 3 Marketed HDAC / PI3K MYC-Altered DLBCL MYC-Driven Solid Tumors Should positive clinical results continue, can be the first drug to successfully address MYC 5

6 PI3Ki Phase 1 study completed enrollment; initial data showed encouraging efficacy in DLBCL, especially in MYC-altered tumors HDACi Targets MYC Transcription Targets MYC Protein Phase 1 study in solid tumors ongoing; focus on MYC-altered tumors Phase 2 ongoing in MYC-altered DLBCL 6

7 Phase 1 Data Establish Drug Properties and RP2D Drug exposure and distribution Rapid and predominant distribution to tissue (10-fold higher than plasma levels) Acceptable safety profile Mild GI effects, fatigue, and thrombocytopenia Tolerability 17% of patients on drug beyond 6 months 8% of treated over 1yr 2 patients treated over 3yrs No DLTs at RP2D Most Common AEs Phase 1 Data Incidence ( % ) Grade 1, 2 Grade 3 Grade 4 Diarrhea Fatigue Nausea Vomiting Thrombocytopenia Neutropenia Hyperglycemia Colitis

8 Phase 1 Responses (DLBCL) Correlated with MYC Alterations * * MYC Alterations BCL2 Alterations *R-907: These two patients were treated with combination of Rituximab and 72 Patients in Phase 1 (25 DLBCL patients 18 patients evaluable for response assessment) 8

9 Rationale for targeting MYC-altered DLBCL in Phase 2 After seeing a MYC correlation in a retrospective analysis of our Phase 1 data, and confirming that finding in subsequent preclinical experiments, we designed our Phase 2 study to target MYC-altered DLBCL Reason #1 Retrospective Analysis of Phase 1 data Reason #2 Subsequent Preclinical Experiments DLBCL Phase 1 Data MYC Positive MYC Negative Unknown Single Dose of in WSU DLCL2 Xenograft Tumors Vehicle 1hr 6hr 12hr 24hr eliminates MYC protein MYC Tubulin CR PR SD Control 1000 Dose Response in WSU DLCL2 in vitro 6hr 24hr Control MYC Tubulin MYC elimination is dose dependent PD Not Evaluable Total Enrolled WSU DLCL2 Xenograft ** exhibits antitumor activity in vivo Multiple MYC Positive patients had Objective Response (CR or PR) ** denotes p-value <

10 Phase 2 Study Design in MYC-altered RR DLBCL Monotherapy N=60 Combination Therapy + Rituximab N=60 1 o Endpoint: ORR 2 o Endpoint: PFS, OS, DoR, Safety Potential for expansion (accelerated registration path) To inform phase 3 trial (full approval path) 10

11 Oral Checkpoint Inhibitor

12 Oral Checkpoint Inhibitor Program PD-L1 / VISTA Indication Solid Tumors Lymphomas Stage of Development Preclinical Phase 1 Phase 2 Phase 3 Marketed is the first and only oral (small molecule) drug candidate to target PD1/PD-L1 12

13 Curis-Aurigene Collaboration Exclusive Partnership for Small Molecules in Immuno-Oncology Small Molecule Antagonists of Immune Checkpoints Aurigene: - Discovery Research and Preclinical Development up to IND - Supply of Phase 1 Clinical Drug Product Curis: - Regulatory and Clinical Development - Global Commercialization, except India & Russia 1 st Collaboration Program Licensed: Small Molecule Checkpoint Inhibitor targeting PD-L1 & VISTA 13

14 Potential PK Advantages of a Small Molecule in Dosing Flexibility Potential PK Advantages of a Small Molecule: 1) More controlled drug exposure 2) Shorter duration of target engagement Small molecules may also minimize immune related side effects (irae) and better enable combination therapy approaches Drug Concentration Dosing Drug Concentration Days Minimum activation required for efficacy Minimum activation required for efficacy Dosing Days 14

15 Preclinical Data Establish Drug Properties In Vitro Dose dependent activation of checkpoint-inhibited T cells In Vivo PK profile consistent in multiple species PD-L1 VISTA (oral dosing) Plasma PK Profile 10 4 PDL-1 Rescue (%) VISTA Rescue (%) Plasma [ng/ml] Mouse Rat Dog Monkey Rescue of IFN-γ production used as a marker for T cell activation Time 24 NOAEL at over 1,000 mg/kg/day In 28-Day Toxicity Studies in Mice & Monkeys 15

16 Preclinical Data Show Potent Efficacy In Vivo Efficacy vs. PD1 Antibody In Models Sensitive to anti-pd1 Efficacy vs. Vehicle In Models Not Sensitive to anti-pd1 MC38 Subcutaneous CRC Model B16/F10 Metastatic Melanoma Model B16/F1 Subcutaneous Melanoma Model B16/F1 Subcutaneous Melanoma Model 40 Vehicle Tumor Volume (mm 3 ) Metastatic Nodules Anti-PD1 * * Tumor Volume (mm 3 ) Vehicle Tumor Volume (mm 3 ) p<0.05 p<

17 Phase 1 Study Design Transition at earlier of Related AE or 4 Cohorts Transition at earlier of DLT, PD, or Clinical Activity Single Patient Cohorts dose doubling per cohort 3x3 Patient Cohorts dose increases 50% per cohort Expansion Phase 150 Patients with solid tumors or lymphoma Open for enrollment in US Preparing ex-us sites for expansion phase In indications without approved PD1/PD-L1 therapies, study will include patients naïve to PD1/PD-L1 17

18 Summary

19 Financials As of March 31, 2016 (in thousands) Cash & Mkt Securities $ 73,100 Erivedge secured debt (non-recourse to Curis) $ 23,300 Shares Outstanding Basic 129,000 Shares Outstanding Diluted* 145,600 *Diluted Shares = 129.0M shares M options 19

20 Milestones Upcoming Data in Two Programs Potential Treatment for MYC-driven Cancer Phase 1 study ongoing in patients with solid tumors initial data in late 2016 / early 2017 Phase 2 study ongoing in DLBCL initial data in st Potential Oral PD1/PD-L1 Antagonist Phase 1 study initiation in process initial data in

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