Company Overview. April Rewriting cancer treatment NASDAQ: EPZM

Transcription

1 Company Overview NASDAQ: EPZM Rewriting cancer treatment

2 Forward Looking Statements This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including statements regarding the Company s future expectations, plans and prospects, and other statements containing the words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in drug discovery and the initiation of future clinical studies or expansion of 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 the results of future trials; expectations for regulatory approvals to conduct trials or to market products; 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 and to achieve the goals set forth in this release; whether orphan drug designation will lead to orphan drug exclusivity or the other potential benefits of orphan drug designation for which we are eligible; other matters that could affect the availability or commercial potential of the Company's therapeutic candidates or companion diagnostics or our ability to transition to a commercial-stage enterprise; and other factors discussed in the "Risk Factors" sections of the Company's Form 10-K filed with the SEC on March 9, 2016 and in the Company's other filings from time to time with the SEC. The forward-looking statements contained in this presentation reflect the Company s current views with respect to future events, and the Company assumes no obligation to update any forward-looking statements. 2

3 5-Year Vision: Rewriting Cancer Therapy through Targeted Medicines for Patients with Unsolved Diseases Four transformative activities through 1 2 Tazemetostat launched globally in both non-hodgkin lymphoma (NHL) and genetically defined solid tumors Transitioned into commercial-stage organization Broad clinical program for tazemetostat Expanded use in earlier lines of therapy, combination regimens and multiple additional tumor types 3 Robust clinical pipeline with at least three new oncology product candidates in development Growing set of preclinical assets behind those 4 Expand our established leadership position in field of epigenetics and chromatin modifying proteins 3

4 Established Proof-of-Concept for Tazemetostat in Hematological Malignancies and Genetically Defined Solid Tumors Durable responses and acceptable safety profile observed in Phase 1 trial 56% Overall Response Rate in relapsed/refractory non-hodgkin lymphoma patients Activity across multiple NHL subtypes in heavily pre-treated relapsed/refractory population 55% Disease Control Rate in patients with genetically defined solid tumors treated at or above recommended phase 2 dose Activity in INI1-and SMARCA4-negative tumors Oral, twice-daily therapy for adults; oral suspension formulation for children Preclinical data support combination potential with multiple therapies Preclinical data support advancement into additional indications 4 *Disease Control Rate: CR, PR or SD and on drug 6 months

5 Robust Portfolio of Oncology Assets Clinical Pipeline Research and Development Pipeline NHL: non-hodgkin lymphoma DLBCL: Diffuse large B-cell lymphoma MLL-r: Mixed lineage leukemia rearranged ALL: Acute lymphoblastic leukemia AML: Acute myeloid leukemia *Eisai holds Japanese development and commercialization rights to tazemetostat **Celgene holds ex-us rights ***GSK holds global development and commercialization rights ****Celgene holds option to license ex-us rights for one target and global rights for the other two targets 5

6 Tazemetostat Acceptable Safety Profile in Phase 1 Patients (n=55) All Events All Treatment-Related All Grades * Grade >3 All Grades Grade >3 ** Asthenia Decreased appetite Thrombocytopenia Nausea Constipation Diarrhea Vomiting Anemia Dry skin Dysgeusia Dyspnea Muscle spasms Abdominal pain Hypophosphatemia Anxiety Depression Hypertension Insomnia Neutropenia Night sweats Peripheral edema Hepatocellular injury NHL patients; 35 solid tumor patients * All AEs with frequency >5% regardless of attribution shown ** All grade >3 treatmentrelated events shown 6 Source: ASH, Dec 2015, data cutoff as of Nov. 7, 2015

7 NHL Therapy Market Expected to Grow to >$9B Worldwide by ,000 estimated new patients diagnosed annually with B-cell NHL in major markets 2 EZH2mut FL 6,000 EZH2wt DLBCL 24,000 EZH2mut DLBCL 6,000 EZH2 wt FL 30,000 Non-GC DLBCL 89,000 7 GC = Germinal Center 1 GBI Research, Non-Hodgkin Lymphoma Therapeutics in Major Developed Markets to 2020, Oct Epizyme commissioned market research

8 Best Response with Tazemetostat in NHL Patients Per Protocol: Response Evaluable* Patients (n=16) DLBCL FL MZL 5/10 (50%) 3/5 (60%) 1/1 CR+PR 9/16 (56%) DLBCL FL MZL Response evaluable: Measurable disease 1 dose 1 post-baseline scan 8 *Per Cheson/IWG Criteria (2007) Source: ASH, Dec 2015, data cutoff as of Nov. 7, 2015

9 Objective Responses Among NHL Patients Dose BID DLBCL FL MZL 9 Per Cheson/IWG Criteria (2007) Food Effects (FE): 200 mg on day -8 and day -1, 400 mg BID from day 1 Source: ASH, Dec 2015, data cutoff as of Nov. 7, 2015

10 Tazemetostat Registration-Supporting Five-Arm Phase 2 Study Underway in NHL Phase 2 Arms in Relapsed/Refractory NHL Germinal Center DLBCL wild-type EZH2 n = 30 Germinal Center DLBCL mutant EZH2 n = 30 Non-Germinal Center DLBCL -- n = 30 Follicular Lymphoma wild-type EZH2 n = 30 Follicular Lymphoma mutant EZH2 n = 30 Study design 5 arms enrolling up to 30 patients each subject to interim futility analysis for each arm Arms enroll independently Primary endpoint Overall response rate by Cheson/IWG criteria (2007) Secondary endpoints Duration of response, PFS, overall survival Global trial with accepted U.S. IND for DLBCL Presentation of interim data planned for mid-2016 Preliminary Epizyme review indicates futility has likely been surpassed in three of five arms; formal confirmation will be made by IDMC 10

11 Significant Need for Targeted Therapies in Genetically Defined Solid Tumors INI1-negative tumors: range of rhabdoid tumors, including malignant rhabdoid tumor 1 One of most aggressive and lethal malignancies in pediatric cancer Occurs most commonly in children, but also occurs in adults Treatment is non-standardized and highly toxic includes chemotherapy, radiation therapy and transplant Median survival of ~1 year 2 SMARCA4-negative tumors, including malignant rhabdoid tumor of ovary 3 Average age of onset is 24 years old Typically unresponsive to platinum-based therapies 2-year survival rate of <35% Synovial sarcoma 4 Occurs most commonly in teenagers and young adults High grade tumor that metastasizes to distant sites in 50-70% of cases 11 1 Horazdovsky R Sarcoma Reinhard, Oncology Reports, Bailey, Pediatric Blood Cancer, Krieg AH, Annals Oncology, 2010.

12 Best Response with Tazemetostat in INI1- and SMARCA4-negative Tumors * Patients censored at time of progression INI1-negative SMARCA4-negative Other solid tumor** ** Four additional other solid tumor patients with pending disease evaluation 12 Source: ESMO, Sep 2015; data cutoff as of August 31, 2015

13 Clinical Activity Seen with Tazemetostat in INI1- and SMARCA4-negative Tumors Tumor * Confirmed response by RECIST 1.1 criteria * Patients who remained on study as of Aug 31, 2015 Dose (mg BID) Best Response Time on study (weeks) INI1-negative Malignant rhadbdoid tumor 800 CR week 8* 65+ SMARCA4- negative 1600 PR week SD week SD week PD week 8 35 Epithelioid sarcoma 800 PR week Malignant rhabdoid tumor of ovary (SCCOHT) 800 SD week PD week PR week 8* SD week Thoracic sarcoma 1600 PD week Source: ESMO, Sep 2015; data cutoff as of August 31, 2015

14 Tazemetostat Registration-Supporting Program Underway in Genetically Defined Solid Tumors Adult Phase 2 N = up to 90 (30 in each arm) Rhabdoid tumors Other INI1-negative tumors Synovial sarcoma Pediatric Phase 1 N = ~ 40 INI1-negative tumors (including rhabdoid tumors) Synovial sarcoma Primary endpoint ORR for rhabdoid and other INI1-negative tumors PFS for synovial sarcoma Secondary endpoint Duration of response, PFS, OS, Safety and PK Dosing: 800 mg BID orally Global study; accepted U.S. IND Primary endpoint Safety, determine recommended Phase 2 dose Secondary endpoint ORR, Duration of response, PFS, OS, PK Dosing: Oral suspension, dose escalation Global study; accepted U.S. IND 14 Rhabdoid tumors: malignant rhabdoid tumor, rhabdoid tumor of the kidney, atypical teratoid/rhabdoid tumor Other INI1-negative tumors: epithelial sarcoma, epithelioid malignant peripheral nerve sheath tumor, extraskeletal myxoid chondrosarcoma, myoepithelial carcinoma, renal medullary carcinoma

15 Phase 2 Study in BAP1-Loss of Function Mesothelioma to Begin in 3Q16 ~12,000 incident mesothelioma patients in major pharmaceutical markets 1,2 BAP1 mutations occur in ~46% of cases 3 Approved first-line therapy, pemetrexed plus cisplatin, provides median OS of ~13 months 4 No approved therapies for second-line, response rates generally <10% 5 BAP1-loss of function mesothelioma shows sensitivity to EZH2 inhibition in xenograft models 6 BAP1-mutant BAP1 wild type Tumor fold change (Normalized to day 1) Tumor fold change (Normalized to day 1) Tumor fold change (Normalized to day 1) Tumor fold change (Normalized to day 1) 15 **P < 0.005; ns, not significant; error bars show means ± s.d. unless otherwise indicated *EPZ011989: EZH2 inhibitor 1 American Cancer Society 2 Park EK Envi Health Perspectives (2011) 3 Farzin Anatomic Pathology (2015) 4 Goudar RK Thera and Clin Risk Mgmt (2008) 5 Tsao AS JCO (2009) 6 LaFave et al., (2015) Nature Medicine

16 Advancing Robust Portfolio of Next-Generation Compounds Pioneering development of small molecule inhibitors for histone methyltransferase (HMT) and other chromatin modifying protein (CMP) targets More than 32,000 CMP inhibitors as part of large proprietary chemical library In-house discovery platform enables rapid identification of important therapeutic targets that can be effectively drugged Sophisticated use of CRISPR technology to prioritize novel targets 5 novel epigenetic targets identified small molecule inhibitors in development At least three oncology product candidates to enter clinic by

17 Collaborations with Leading Pharmaceutical and Diagnostic Companies Worldwide option on compounds against two HMT targets Ex-U.S. option on one HMT target Global collaboration on pinometostat Global development and commercialization rights to compounds against three targets, including first-in-class PRMT5 inhibitor Research collaboration completed; preclinical evaluation ongoing Collaboration to develop companion diagnostic for detection of common EZH2 gain-of-function mutations in NHL In use in ongoing phase 2 NHL study to identify patient EZH2 mutation status Development and commercialization rights to tazemetostat in Japan; right of first negotiation for rest of Asia 17

18 Multiple Clinical Milestones Anticipated throughout 2016 Upcoming Milestone Timing Initiate phase 1b/2 combination study of tazemetostat in NHL with R-CHOP 2Q 2016 Initiate combination study of tazemetostat with anti- PD1-1 or PDL-1 agent Present interim data from 5-arm phase 2 study of tazemetostat in NHL Mid-2016 Mid-2016 Initiate phase 2 study of tazemetostat in BAP1-loss of function mesothelioma 3Q 2016 Present interim data from 3-arm phase 2 study of tazemetostat in adults with genetically defined solid tumors 2H 2016 Present phase 1 pediatric pinometostat data 2H 2016 Present updated phase 2 from 5-arm phase 2 study of tazemetostat in NHL Late

19 Rewriting Cancer Therapy through Targeted Medicines for Patients with Unsolved Diseases Expansive tazemetostat clinical development program actively enrolling Multiple readouts from registration-supporting phase 2 trials of tazemetostat in 2016 Wholly owned small molecule inhibitors in development against five novel targets Top-tier pharmaceutical collaborations advancing seven programs Financial strength to fund operations through multiple value-accretive milestones 19