Leerink Global Healthcare Conference February 2015 2013 - PowerPoint PPT Presentation

Personalized Therapeutics Ÿ Ÿ The Power of Epigenetics Leerink Global Healthcare Conference February 2015

2013 Accomplishments Forward Looking Statements � This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding our strategy, future operations, prospects, plans and objectives of management, are forward- looking statements. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘potential,’’ ‘‘will,’’ ‘‘would,’’ ‘‘could,’’ ‘‘should,’’ ‘‘continue,’’ 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 may differ materially from those indicated by such forward- looking statements as a result of various important factors, including: uncertainties inherent in the initiation of future clinical studies, expectations of expanding ongoing clinical studies, availability and timing of data from ongoing clinical studies, whether interim results from a clinical trial will be predictive of the final results of the trial or results of early clinical studies will be indicative of the results of future studies, expectations for regulatory approvals, development progress of the Company’s companion diagnostics, availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements, other matters that could affect the financial performance of the Company, other matters that could affect the availability or commercial potential of the Company’s therapeutic candidates or companion diagnostics and other factors discussed in the "Risk Factors" section of the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 6, 2014. � 12 F EBRUARY 2015 � 2 �

Pioneers and Leaders in the Field of Histone 2013 Accomplishments Methyltransferase (HMT) Inhibitors � � • Clinically validated targets � – Clinically demonstrated objective responses in non-Hodgkin lymphoma (NHL), malignant rhabdoid tumor (MRT), and MLL-r leukemia with the first two HMT inhibitors ever to enter clinical trials (EPZ-6438 and EPZ-5676) � – Complete responses in Phase 1 studies with EZH2i and DOT1Li � • Robust Intellectual Property � – Chemical matter against 13 of 20 prioritized targets within the Clinically advancing proprietary HMT methylome � inhibitor candidates from an efficient – Eight issued patents with first expiries research operation with deep scientific, in 2032 � clinical and managerial expertise � • Strong financial position � – Funded until at least mid-2016, prior to including any potential future milestone payments � � 12 F EBRUARY 2015 � 3 �

Seasoned Management Team with Deep Industry 2013 Accomplishments Expertise � • 20 years at Merck in • Former Vice President, positions of increasing Cancer Biology at GSK � • Held scientific positions of leadership, including VP of Licensing and External increasing leadership at Research � Merck and BMS � • Former Director of Novel • Held faculty position at Therapeutics at the Broad University of Chicago Institute of MIT and Harvard � Pritzker School of Medicine � • B.A. from Spring Arbor • B.S. from Seton Hall College, Ph.D. from University, Ph.D. from Robert Gould, Ph.D. � Robert Copeland, Ph.D. � President and CEO � University of Iowa � President of Research � Princeton University � and CSO � • Nearly 20 years of financial • Former Vice President of experience in life sciences Oncology Development at field � J&J � • Former Managing Director, • Former Senior Vice Healthcare Investment President of Oncology at Banking in Life Sciences GSK � • Former fellow at Dana- Group at RBC Capital Markets � Farber, NCI and FDA � • B.A. from Yale University, • B.A. from Johns Hopkins, Peter Ho, M.D., Ph.D. � M.B.A. from Harvard M.D. and Ph.D. from Yale Chief Development Officer � Business School � University School of Andrew Singer � Medicine � Chief Financial Officer � � 12 F EBRUARY 2015 � 4

Pipeline of First-In-Class Personalized 2013 Accomplishments Therapeutics � Pre-clinical Development Clinical Development EPZ-6438 EZH2 ü Phase 1 dose expansion ongoing NHL and INI1- q Initiation of three studies planned Deficient Tumors 2015 (2 Phase 2; 1 Phase 1) EPZ-5676 DOT1L ü Phase 1 dose escalation ongoing Acute Leukemias with MLL-r expansion stage ü Phase 1 peds study ongoing PRMT5 ü Development candidate (GSK Target 1) milestone in 2013 ü Lead candidate milestone in GSK Target 2 2014 ü Lead candidate milestone in GSK Target 3 2014 Novel HMT Targets q Pipeline update 1H15 <200 nM Solid Tumors <50 nM Novel HMT Targets Hematologic Malignancies 12 F EBRUARY 2015 � 5 �

2014: Clinical Validation of HMT Targets, Pipeline 2013 Accomplishments Progress � Clinical Progress ü Demonstrated durable objective responses in Phase 1 study of EPZ-6438 (EZH2i) in NHL and solid tumor patients • PR or better in 3 of 5 DLBCL patients, including 1 ongoing CR at more than 41 weeks ü Demonstrated clinical and biological activity in Phase 1 study of EPZ-5676 (DOT1Li) in adult MLL-r patients • Two complete responses (CR) and one partial response (PR) achieved in Phase 1 dose escalation study ü Initiated expansion cohorts in multiple programs • Six additional patients enrolled at 800 mg in EPZ-6438 Phase 1 study dose escalation expansion cohort, currently enrolling up to six patients at 1600 mg in expansion cohort ü Initiated EPZ-5676 Phase 1 study in pediatric MLL-r patients Pipeline Milestones ü Demonstrated in vivo and in vitro activity of first-in-class PRMT5 inhibitor in models of mantle cell lymphoma in pre-clinical study data presented at ASH – 1 st target in GSK collaboration ü $2 million lead candidate milestone for 2 nd target in GSK collaboration; $4 million lead candidate milestone and license payment for 3 rd target in GSK collaboration ü Patent notice of allowance granted for PRMT5 inhibitor; patent applications published on novel chemical matter against multiple HMT targets, including CARM1, PRMT3, PRMT6, PRMT8 � 12 F EBRUARY 2015 � 6

2013 Accomplishments 2015: Focus On Execution � • EPZ-6438 – Complete accrual of up to 12 patients in Phase 1 dose escalation expansion cohorts (1Q15) � – Initiate Phase 2 studies in partnership with Eisai - NHL study with prospective stratification of mutant and wild type EZH2 patients � • EPZ-5676 – Complete accrual of up to 20 patients at 54 mg/m 2 /day (2H15) � – Complete enrollment in Phase 1 pediatric study (2H15) � • Progress Pipeline – Present discovery research on HMT targets at AACR annual meeting (abstracts submitted) � – Additional patent issuances expected in 2015 � � 12 F EBRUARY 2015 � 7

EPZ-6438 (E7438) � 2013 Accomplishments First-in-Class, Oral, Selective Inhibitor of EZH2 � • Potent and selective for mutant and wild type EZH2 � 2 • Durable objective responses demonstrated in Phase 1 study: � – PR or better in 4 of 10 evaluable NHL patients to date � • PR or better in 3 of 5 DLBCL patients, including 1 ongoing CR at more than 41 weeks � EPZ-6438 ( µ M) – Ongoing PR in 1 of 2 INI1-deficient patients � 0 1 H3K27Me1 • Unmet need in NHL: � EZH2 H3K27Me2 Products – H3K27Me3 Poor prognosis for patients who fail R-CHOP � H3K4Me3 – Need for active drugs that avoid long-term H3K9Me3 H3K36Me2 myelosuppression and immunosuppression � H3K79Me2 • Continuing to explore a broad spectrum of H3K27Ac H3 cancer indications � 8 12 F EBRUARY 2015 � �

2013 Accomplishments EPZ-6438 First-in-Human Phase 1 Study � Study design: Open-label, multicenter Primary Endpoint • Single agent, oral BID dosing, • MTD/RP2D 28-day cycles Secondary Endpoints • Histologic/cytologically confirmed • Safety advanced solid tumors or B-cell • PK lymphomas • Anti-tumor activity • “3+3” dose-escalation design Safety assessments: • Baseline, D1 and D15 of every cycle 1600 mg (n = 6) Tumor assessments : 800 mg • Baseline and every 8 weeks (n = 6) 400 mg PK samples : (n = 3) 200 mg • Cycle 1, D1 and D15; Cycle 2 D1 (n = 3) 100 mg Skin biopsies : (n = 6) • Baseline and Cycle 2 D1 Study initiation: June 2013 Data cut-off: October 20, 2014 BID, twice daily; D, day; MTD, maximum tolerated dose; PK, pharmacokinetics; RP2D, recommended Phase 2 dose 9 ¡ 12 F EBRUARY 2015 � 9 �