Jefferies Healthcare Conference

Transcription

1 0 Jefferies Healthcare Conference 3 June 2015 NASDAQ: CRIS

2 Forward Looking & Other Important Cautionary 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 forward-looking 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 Quarterly Report on Form 10-Q for the period ended March 31, 2015 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. 1

3 Curis Leading biotech company that effectively develops and expects to commercialize oncology drugs for significant patient benefit and access Small molecule antagonists of immune checkpoints Aurigene Multiple small molecule programs targeting checkpoint receptor-ligand interactions ongoing PDL1, orally available small molecule disrupts PDL1/PD1 interaction: IND filing expected in 2015 Drug candidates to address hematologic cancers CUDC-907, clinical activity in diffuse large B cell lymphoma: Phase 2 expected in Q IRAK4, orally available small molecule inhibitor: IND filing expected Q Erivedge for advanced basal cell carcinoma Roche/Genentech Approved in the US, EU and multiple other countries worldwide, royalty revenues to Curis Development in idiopathic pulmonary fibrosis planned 2

4 Pipeline: Novel, Targeted Cancer Therapeutics Advancing key proprietary programs Program Target Indication Preclinical Phase 1 Phase 2 Phase 3 Market Key Proprietary Programs CUDC-907 HDAC/PI3K DLBCL Phase 1 Expansion Breast Cancer & NUT Midline Carcin. Phase 1 PD-L1i* PD-L1 Multiple cancers Pre-IND IRAK4i* IRAK4 DLBCL Waldenstrom s macroglobulinemia Pre-IND Partnered Program Erivedge Hedgehog Advanced Basal Cell Carcinoma Idiopathic Pulmonary Fibrosis (IPF) Phase 2** Approved in > 50 Countries Phase Phase 1/22 Other Proprietary Programs CUDC-427 IAP Lymphoma Phase 1 CUDC-305 Hsp90 Cancers Phase 1 Phase 1b/2 * Subject to Curis expectations to exercise options to exclusively license the Development Candidates from each program ** IND filed in June, No patients enrolled; recruitment suspended pending modification of trial design. 3

5 CUDC-907 Potent HDAC and PI3K enzyme inhibition in one oral small molecule High tissue distribution significant levels of enzyme inhibition activity Active in patients with DLBCL, including transformed follicular DLBCL HDACi PI3Ki IC50 (nm) HDAC PI3K Enzyme Alpha Delta Beta Gamma IC50 (nm)

6 CUDC-907 in Hematologic Cancer Phase 1 trial completed 57 patients with relapsed/refractory lymphoma and multiple myeloma 40 patients in dose escalation, 17 patients in expansion cohorts (DLBCL, HL, MM) Recommended Phase 2 dose and schedule determined 60mg daily dose administered 5 days on / 2 days off; 21-day treatment cycles PK and PD demonstrate drug exposure and target engagement High levels of drug exposure in tumor tissue vs. plasma HDAC and PI3K enzyme modulation observed in patient PBMC samples Safe and tolerable at recommended dose Most frequent AEs ( 2 patients): diarrhea, fatigue, thrombocytopenia DLTs of diarrhea and hyperglycemia Clinical benefit merits continued development Objective responses in patients with DLBCL and Hodgkin s lymphoma Stable disease in patients with Hodgkin s lymphoma and multiple myeloma 5

7 CUDC-907 PK Profile CUDC-907 rapidly distributes to tissues including tumor Preclinical PK Profile Balb/c Mice Clinical PK Profile 5/2 Schedule, 60mg dose: Plasma & Tumor PK TUMOR TISSUE PLASMA PLASMA 6

8 Overall Activity in Patients with Lymphoma * 7

9 Clinical Benefit in Patients with DLBCL 16 patients with DLBCL enrolled, 10 evaluable for response Effective disease control, including partial and complete responses Noteworthy benefit in patients with transformed DLBCL Time to Response and Durability (days) Max Tumor Regression (%) Ongoing Ongoing Ongoing Ongoing, proceeded to ASCT Days

10 Case Report Patient with RR t-fl/dlbcl Subject ID Tumor Type Age/Gender Response to CUDC-907 t-fl/dlbcl 71 / Male PR (Cycle 10) CR (Cycle 12) Duration on CUDC Days + Treatment Status Ongoing Prior Treatment Best Response 1. R-CHOP 2011 CR 2. R-ICE 2012 PR 3. ASCT 2012 CR Baseline PET/CT Cycle 10 PET/CT (-52%) 9

11 CUDC-907 in Diffuse Large B-cell Lymphoma Phase 1 dose escalation completed, expansion in DLBCL ongoing Monotherapy and combination with rituximab arms open Recommended Phase 2 dose and schedule determined 60mg dose on 5/2 schedule Safe and tolerable: manageable diarrhea, fatigue and thrombocytopenia Novel tissue distribution profile: high drug exposure Orphan drug designation for DLBCL granted by FDA Planned end-of-study meeting request with the FDA Registration-directed trial opportunity in relapsed/refractory disease Phase 2 monotherapy trial in patients with transformed DLBCL Phase 2 randomized trial in combination with rituximab Earliest trial start date in Q

12 Curis Immuno-oncology Strategy Small molecule antagonists of checkpoint receptor-ligand interactions Up to five years exclusive partnership with Aurigene Sequences from interaction interface High affinity peptides PD1/PDL1 receptor-ligand interaction Truncation & modification Structure-based design: small molecule antagonists generated based on interface of receptor-ligand interaction Small molecule library Identify small molecule candidate 11

13 Ability to Optimize Potency and Desired Selectivity Biology Disease Discovery PDL1 TIM3 LAG3 VISTA 12

14 PD-L1 Antagonist Properties Disrupts interaction of both mouse and human PD1/PD-L1 Potent antagonism of PD-L1 mediated inhibition of T lymphocytes EC50 ~15 nm for rescue of lymphocyte proliferation EC50 ~20 nm for INF-γ production Excellent drug-like properties with oral bioavailability of ~50% Excellent expected safety profile No interaction with CYP enzymes No alteration of herg activity Clean in receptor and enzyme panels No adverse events observed 14-day high dose administration in mice 13

15 PD-L1 Antagonist In vivo PD Profile Circulating INF-γ production in mice after oral administration Lead candidate (mg/kg) J43 anti-mouse PD1 antibody 14

16 PD-L1 Antagonist Properties In vivo activity profile Average metastatic counts B16 melanoma model Average metastatic counts 73% reduction in metastasis p<0.05 Metastasis counts in Individual animals p< Vehicle LC, 10mpk PO Vehicle LC, 10mpk PO In vivo Efficacy (MC38 Model) p<0.05 p<0.01 LC: Lead Candidate J43 anti-mouse PD1 antibody 15

17 PD-L1 Antagonist Properties 14 day repeat dose safety profile mouse Mortality : No mortality Clinical Signs of Toxicity : No abnormalities detected Body weight : No test item related changes Food Consumption : No test item related changes Hematology : No test item related changes Clinical Chemistry : No test item related changes Gross Pathology : No treatment related changes Organ weights : No treatment related changes Histopathology : No treatment related changes 16

18 PD-L1 Small Molecule Antagonist Selectively binds to target immune checkpoint ligand (PD-L1) and potently disrupts interaction with receptor (PD1) Induces proliferation of T-cells and IFN-gamma production Clean off-target profile (enzyme, receptors, ion channels, kinases) Orally bioavailable with good PK properties in mice Clean preliminary in vivo safety profile Induces IFN-gamma production in vivo after oral administration Anti-tumor activity in multiple syngeneic tumor models In preparation for GLP toxicology studies IND filing expected in Q4,

19 IRAK4 - A Target for Cancer Therapy Toll and IL-1 receptor signaling pathway implicated in certain cancers MYD88 adaptor protein transduces receptor signaling to IRAK4 IRAK4 kinase activity, through IRAK1 is critical for NF-κB activation Activating MyD88 Mutations in human cancer ~30% in ABC-DLBCL, ~90% in Waldenstrom's macroglobulinemia, ~5-10% in CLL IL-1R TLRs Cytokines Plasma membrane MYD88 IRAK4 IRAK1 PO 4 p50 NF-κB p65 Nucleus Survival 18

20 Lead Molecules are Active In Vivo Cancer and inflammatory disease models Active in in vivo oncology and inflammatory disease models LC = Lead Candidate IRAK4 inhibitor Lef = Leflunomide Thyop = Theyophilline, IP administration 19

21 Lead IRAK4 Small Molecule Inhibitors Potent and selective inhibitors of IRAK4: biochemical IC 50 in low nm Potent cell-based activity and readouts Inhibit IRAK1 phosphorylation in cell-based assays Inhibit TNF-α production in human PBMC Inhibit proliferation of DLBCL cell lines with MYD88 mutation in culture Orally bioavailable with excellent PK properties drug-like molecules Effective in vivo anti-tumor activity mutant DLBCL model Active in in vivo inflammatory disease models arthritis Safety studies ongoing IND filing expected in Q1,

22 Erivedge - Expanding Revenue Opportunity Developed under Genentech and Roche collaboration Erivedge (vismodegib) Oral inhibitor of Hedgehog signaling pathway Approved for treatment of advanced basal cell carcinoma (2012) Milestone and royalty-based revenue stream for Curis Global net sales: continued year-over-year growth ~ $30 million in launch year (2012) net sales recorded by Genentech and Roche ~ $80 million in 2013 ~$136 million in 2014 Royalty revenue to Curis $6.8 million in 2014 royalties to Curis through December 31, 2014 $59 million in milestones earned Other development by Genentech and Roche IND filed for Idiopathic Pulmonary Fibrosis: June 2014 Roche indicated potential trial initiation with amended protocol 21

23 Expected 2015 Milestones CUDC-907 Ongoing study in patients with transformed DLBCL as monotherapy Ongoing study in combination with rituximab Ongoing Phase 1 study in patients with solid tumors interim data in Q Initiation of Phase 2, registration-directed trial in Q Preclinical assessment of activity in combination with immune checkpoint inhibitors PD-L1 antagonist oral small molecule immuno-oncology candidate IND filing Q IRAK4 inhibitor oral small molecule Development candidate(s) Q IND filing Q

24 Summary Financial Data March 31, 2015 (000 s) Cash, cash equivalents, investments $ 107,200 Erivedge secured debt (non-recourse to Curis) $ 27,400 Basic shares outstanding 128,300 Fully-diluted shares outstanding* 141,000 Net loss $ (18,729) * - Difference between fully-diluted and basic shares outstanding is comprised solely of options to purchase common stock. 23

25 NASDAQ: CRIS 24