Epizyme Announces Third Quarter 2015 Financial Results and Provides Corporate Update

On November 9, 2015 Epizyme, Inc. (NASDAQ:EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapies for cancer patients, reported business highlights and operating and financial results for the third quarter of 2015 (Press release, Epizyme, NOV 9, 2015, View Source [SID:1234508107]).

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"Epizyme is well-positioned, with tazemetostat achieving proof of concept in both hematological malignancies and genetically defined solid tumors, while demonstrating an acceptable safety profile," said Robert Bazemore, President and Chief Executive Officer, Epizyme. "Epizyme is executing on our strategic goal of bringing tazemetostat to patients as quickly as possible, and we are operating from a sound financial position. Our vision is to build Epizyme into a multi-product oncology company bringing targeted epigenetic therapies to patients."

Program Summaries

Tazemetostat:

In 2015, proof of concept was achieved in patients with relapsed or refractory B-cell Non-Hodgkin Lymphoma (NHL) and in patients with advanced solid tumors. Interim data from NHL patients enrolled in an ongoing phase 1 study were presented at the International Conference on Malignant Lymphoma meeting in June 2015 showing a 60 percent response rate in the 15 evaluable NHL patients. Data from the solid tumor patients from the same study were presented at the European Cancer Congress meeting in September 2015 reporting a 55 percent disease control rate in the nine patients with INI1-negative or SMARCA4-negative tumors who were treated at or above the recommended phase 2 dose of 800 mg orally administered twice daily. In these presentations of interim data from the ongoing phase 1 study, Epizyme reported that tazemetostat had an acceptable safety profile.

Epizyme is currently conducting a registration-supporting 5-arm phase 2 clinical study of tazemetostat as a monotherapy in patients with relapsed or refractory B-cell NHL, prospectively stratified by cell of origin and EZH2 mutational status. Epizyme expects to enroll approximately 150 patients in this study and to present interim data from the study at a medical conference by mid-2016.

Epizyme also plans to initiate two registration-supporting clinical trials in patients with INI1-negative tumors or synovial sarcoma, including a registration-supporting phase 2 study of tazemetostat in adult patients, and a proof-of-concept phase 1 trial in pediatric patients, both of which are on track to begin in the fourth quarter of 2015.

In the first half of 2016, Epizyme plans to initiate additional clinical evaluations of tazemetostat as a combination therapy, including a phase 1/2 study with R-CHOP in front-line high-risk patients with diffuse large B-cell lymphoma and a combination study with a B-cell signaling agent or immuno-oncology agent in B-cell lymphoma.

Pinometostat:

A dose-escalation study of pinometostat in pediatric patients with MLL-r acute leukemia is ongoing and enrollment in the dose escalation cohorts is expected to complete in the fourth quarter of 2015. Epizyme anticipates presenting final study results after all patients conclude treatment and related data analyses are complete.

Epizyme and Celgene are exploring the potential clinical development of pinometostat in combination with other agents based on encouraging preclinical data.

Third Quarter 2015 Financial Results

Collaboration Revenue: Collaboration revenue was $0.4 million in the third quarter of 2015 and $2.0 million for the nine months ended September 30, 2015 compared with $8.2 million and $31.1 million in the comparable periods of 2014. The decrease in collaboration revenue primarily reflects the completion of a significant portion of our performance obligations under our collaborations during 2014 and achievement of a $3.0 million milestone under our agreement with GlaxoSmithKline during 2014. We expect to recognize an additional $2.4 million of deferred revenue related to the Celgene agreement through December 31, 2016 as we complete our pinometostat phase 1 clinical trials.

R&D Expenses: Research and development expenses were $16.8 million for the third quarter 2015 and $94.4 million for the nine months ended September 30, 2015 compared to $22.2 million and $55.1 million for the comparable periods of 2014. Costs related to the expansion of tazemetostat clinical trials and related EZH2 activities and the $40.0 million upfront payment to Eisai in the first quarter of 2015 were partially offset by reductions in external spending on pinometostat and discovery and preclinical programs during the nine months ended September 30, 2015 compared to the same period of the prior year. Epizyme expects development expenses will continue to increase in 2015 as compared to 2014 since the Company is now solely responsible for funding tazemetostat clinical trials and related development costs outside of Japan. These increased expenses are likely to be partially offset by decreases in spending for pinometostat.

G&A Expenses: General and administrative expenses were $6.7 million for the third quarter of 2015 and $17.9 million for the nine months ended September 30, 2015 compared with $5.7 million and $15.9 million in the comparable periods in 2014. The increase in G&A expense was primarily related to higher personnel-related expenses and an increase in patent filings and related professional fees.

Net Loss: Net loss was $23.1 million in the third quarter 2015 and $110.2 million for the nine months ended September 30, 2015 compared with $19.7 million and $40.0 million in the comparable periods in 2014.

Cash and Cash Equivalents: Cash and cash equivalents as of September 30, 2015 were $229.9 million, compared with $190.1 million as of December 31, 2014. Epizyme’s follow-on public offering in March 2015 raised $117.0 million in proceeds before expenses and the exercise of the underwriters’ over-allotment option provided an additional $13.7 million in proceeds before expenses. The company received an upfront payment of $10.0 million under the amended and restated collaboration and license agreement with Celgene in July 2015. The company expects that, based on its current operating plan, cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements through at least the end of the second quarter of 2017.

Shares Outstanding: Shares outstanding as of September 30, 2015 were 41.7 million. Weighted average shares outstanding were 41.5 million and 39.2 million for the three and nine months ended September 30, 2015 respectively and 33.7 million and 32.6 million for the comparable periods in 2014.

Conference Call Information

Epizyme will host a conference call and live audio webcast today at 8:00 a.m. ET to discuss third quarter 2015 financial results and provide a corporate update. To participate in the conference call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 67279629. The live webcast can be accessed under "Events and Presentations" in the Investor Relations section of the Company’s website at www.epizyme.com

The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About Epizyme, Inc.

Epizyme, Inc. is a clinical-stage biopharmaceutical company creating novel epigenetic therapeutics for cancer patients. Epizyme has built a proprietary product platform that the Company uses to create small molecule inhibitors of chromatin modifying proteins (CMPs), such as histone methyltransferases or HMTs. CMPs are part of the system of gene regulation, referred to as epigenetics, that controls gene expression. Genetic alterations can result in changes to the activity of CMPs, making them oncogenic (cancer-causing). By focusing on the genetic drivers of cancers, Epizyme’s targeted science seeks to match the right medicines with the right patients.

For more information, visit www.epizyme.com and connect with us on Twitter at @EpizymeRx.

About EZH2 in Cancer

EZH2 is a histone methyltransferase that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include Non-Hodgkin Lymphoma, rhabdoid tumors and other INI1-deficient cancers such as epithelioid sarcomas and synovial sarcoma as well as a range of other solid tumors.

About Tazemetostat

Epizyme is developing tazemetostat for the treatment of patients with Non-Hodgkin Lymphoma and patients with INI1-deficient solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In many human cancers, aberrant EZH2 enzyme activity results in misregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non-Proprietary Name (INN) for EPZ-6438.

Additional information about this program, including clinical trial information, may be found here: View Source

About Pinometostat

Epizyme is developing pinometostat, a small molecule inhibitor of DOT1L created with Epizyme’s proprietary product platform, for the treatment of patients with acute leukemia in which the MLL gene is rearranged due to a chromosomal translocation (MLL-r). Due to these rearrangements, DOT1L is misregulated, resulting in the increased expression of genes causing leukemia. Pinometostat is the WHO International Non-Proprietary Name (INN) for compound EPZ-5676.

Epizyme believes that pinometostat was the first HMT inhibitor to enter human clinical development. Epizyme is currently conducting a phase 1 study of pinometostat in pediatric patients with rearrangements of the MLL gene. Additional information about this ongoing phase 1 study can be found here:

View Source

Pinometostat has been granted orphan drug designation for the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) by the Food and Drug Administration in the U.S. and by the European Commission in Europe.

Epizyme retains all U.S. rights to pinometostat and has granted Celgene an exclusive license to pinometostat outside of the U.S.

UPDATE — ArQule Presents Data on Tivantinib and Proprietary Pipeline at AACR-NCI-EORTC Conference

On November 09, 2015 ArQule, Inc. (Nasdaq:ARQL) reported the results of preclinical and clinical studies focusing on tivantinib, ARQ 087, ARQ 092, and ARQ 751 (Press release, ArQule, NOV 9, 2015, View Source [SID:1234508132]). The data were presented at the AACR (Free AACR Whitepaper)-NCI-EORTC meeting on November 7th, 2015. The poster presentations can be accessed in the "Investor and Media" section of our website, www.arqule.com, under "Recent Data Presentations."

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For the first time, data from an exploratory sub-analysis of the MARQUEE trial with tivantinib in non-small cell lung cancer in patients with advanced disease and epidermal growth factor receptor (EGFR) mutations were presented. The data showed tivantinib, when added to erlotinib, increased progression-free survival to 13 months compared to 7.5 months in the erlotinib plus placebo arm. The sub-analysis included 109 patients of which 56 were in the combination tivantinib plus erlotinib arm of the trial. The data were highlighted in an AACR (Free AACR Whitepaper) press release and press conference.

"The data from the sub-analysis of the MARQUEE trial supports our focus on precision medicine," said Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "Although the study did not meet its primary endpoint, this analysis is encouraging and offers evidence that tivantinib when dosed in a specific patient population can provide substantial benefit."

Additionally, the company presented pre-clinical and clinical data on its early stage proprietary pipeline that support ArQule’s efforts to address the needs of patients in therapeutic areas of high unmet need through precision medicine. Data presented on FGFR inhibitor, ARQ 087, demonstrate that FGFR2 dysregulation correlates with efficacy and supports the on-going phase 2 trial in intrahepatic cholangiocarcinoma. Similarly, data presented on AKT inhibitors, ARQ 092 and ARQ 751, demonstrate that both drugs inhibit AKT and provide strong rationale for further studies in patients harboring AKT1 and PI3K mutations.

"Data presented at this year’s AACR (Free AACR Whitepaper)-NCI-EORTC conference are part of ArQule’s translational effort to connect preclinical and clinical research and guide a true precision medicine endeavor," said Giovanni Abbadessa, Vice President of Clinical Development, Translational Medicine and Medical Affairs at ArQule. "Both ARQ 092 and ARQ 087 have shown single-agent activity in vitro, in vivo and in patients in cancers driven by genetic alterations of their respective targets, AKT and FGFR. In addition, these pre-clinical data find confirmation in the clinical results achieved by ARQ 087 and ARQ 092 in their respective phase 1 clinical trials in genetically-altered endometrial and breast cancer and in FGFR2-driven cholangiocarcinoma, respectively. Combinability data reported for both experimental drugs with standard therapies may allow even more development options for the future."

Precision Medicine

Tivantinib is enrolling in two biomarker-driven phase 3 trials, METIV-HCC and JET-HCC. ARQ 087 is enrolling in a biomarker-driven phase 2 trial in intrahepatic cholangiocarcinoma (iCCA) with FGFR translocations. ARQ 092 is enrolling in a phase 1b biomarker-driven trial in patients with AKT and PI3K activating mutations including patients with breast, endometrial and ovarian cancers.

About MET and tivantinib (ARQ 197)

Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in Phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth factor receptor) antibodies such as cetuximab and panitumumab.

Pre-clinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been generally well tolerated and has shown clinical activity in a number of tumors. Tivantinib has not yet been approved for any indication in any country.

In December 2008, ArQule and Daiichi Sankyo signed a license, co-development and co-commercialization agreement for tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan.

About the AKT Pathway, ARQ 092 and ARQ 751

ARQ 092 and ARQ 751 are orally available, selective small molecule inhibitors of the AKT kinase. The AKT pathway when abnormally activated is implicated in multiple oncogenic processes such as cell proliferation and apoptosis. This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity, which has been linked to a variety of cancers as well as to select non-oncology indications.

ARQ 092, the lead compound in ArQule’s AKT program, has completed Phase 1a clinical testing and has advanced into Phase 1b expansion testing in cohorts of patients with endometrial cancer, lymphoma and tumors harboring either AKT or PI3K mutations. A number of next-generation compounds in the Company’s AKT program are in early to late stages of pre-clinical development. The company plans to file an Investigational New Drug (IND) application by the end of 2015 for ARQ 751, a next generation AKT inhibitor.

About FGFR and ARQ 087

ARQ 087 is a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor ("FGFR") family with demonstrated efficacy in FGFR2 amplified tumors. The FGFR pathway is disrupted in several ways in human cancer, thus providing numerous therapeutic targets for an inhibitor of this pathway. ARQ 087 has demonstrated inhibition of tumor growth and downstream signaling in vivo in tumors whose growth is driven by these targets.

Signals of single agent activity with this compound were observed in Phase 1a testing. Phase 1b expansion cohorts with ARQ 087 include patients with cholangiocarcinoma and adrenocortical tumors, as well as those with FGFR translocations, amplification and mutations. Clinical development of ARQ 087 has advanced into Phase 2 for intrahepatic cholangiocarcinoma ("iCCA") following the observation of two confirmed partial responses in this patient population in the Phase 1 portion of the program.

10-Q – Quarterly report [Sections 13 or 15(d)]

(Filing, 10-Q, Galectin Therapeutics, NOV 9, 2015, View Source [SID:1234508110])

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10-Q – Quarterly report [Sections 13 or 15(d)]

(Filing, 10-Q, ImmunoCellular Therapeutics, NOV 9, 2015, View Source [SID:1234508160])

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Foundation Medicine and Collaborators to Present New Clinical Data Supporting Comprehensive Genomic Profiling in Advanced Sarcomas and Hematologic Malignancies with FoundationOne® Heme

On November 9, 2015 Foundation Medicine, Inc. (NASDAQ:FMI) reported that the company and its collaborators will present three oral and four poster presentations at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place December 5 – 8, 2015 in Orlando, Florida (Press release, Foundation Medicine, NOV 9, 2015, View Source [SID:1234508109]). Collectively, the presentations will focus on the application of FoundationOne Heme to identify druggable genomic alterations, inform personalized treatment strategies and improve clinical outcomes across a broad range of sarcomas and hematologic malignancies.

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FoundationOne Heme is a comprehensive genomic profile that analyzes DNA in 405 genes and RNA in 265 genes that are most commonly altered in hematologic malignancies and sarcomas. The assay provides oncologists and pathologists with clinically relevant genomic alterations to guide treatment options for patients based on the genomic profile of their cancer.

The schedule for oral presentations by Foundation Medicine and/or its collaborators is as follows:

Session Date & Time: Saturday, December 5, 2015, from 12:00-1:30 p.m. ET
Presentation Time: 12:45 p.m. ET
Title: Genomic and Proteomic Analysis of Primary Chemoresistance and Induction Failure in Acute Myeloid Leukemia
Publication Number: 88
Location: Tangerine 3 (WF3-4), Level 2
Session: 617 – Acute Myeloid Leukemia: Biology, Cytogenetics and Molecular Markers in Diagnosis and Prognosis: Omics-based Approaches for the Identification of Novel Genetic Modalities in AML
Presenter: Fiona Brown, Ph.D., research fellow, Memorial Sloan-Kettering Cancer Center
Collaborators: Memorial Sloan-Kettering Cancer Center, Dana-Farber Cancer Institute, Children’s Hospital Boston, Children’s Oncology Group, Fred Hutchinson Cancer Research Center, The University of Texas MD Anderson Cancer Center, The Ohio State University Comprehensive Cancer Center, Harvard Medical School

Session Date & Time: Sunday, December 6, 2015, from 4:30-6:00 p.m. ET
Presentation Time: 5:45 p.m. ET
Title: Comprehensive Genomic Profiling of Multiple Myeloma in the Course of Clinical Care Identifies Targetable and Prognostically Significant Genomic Alterations
Publication Number: 369
Location: W224ABEF
Session: 651 – Myeloma: Biology and Pathophysiology, Excluding Therapy: Novel Technologies to Evaluate Biology and Prognosis
Presenter: Christopher Heuck, M.D., assistant professor of medicine, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences
Collaborators: Myeloma Institute for Research and Therapy

Session Date & Time: Monday, December 7, 2015 from 7:00-8:30 a.m. ET
Presentation Time: 7:00 a.m. ET
Title: Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms
Publication Number: 481
Location: W331
Session: 635 – Myeloproliferative Syndromes: Basic Science I
Presenter: Benjamin Durham, M.D., research fellow, Memorial Sloan-Kettering Cancer Center
Collaborators: Memorial Sloan-Kettering Cancer Center

The schedule for poster presentations by Foundation Medicine and/or its collaborators is as follows:

Poster Display: Saturday, December 5, 2015 from 9:00 a.m.-7:30 p.m. ET
Poster Presentation: Saturday, December 5, 2015 from 5:30-7:30 p.m. ET
Title: Integrated DNA/RNA Profiling for Somatic Alterations in Adult B-cell ALL
Publication Number: 1422
Poster Display Location: Hall A2-A3
Poster Presentation Location: Hall A2-A3
Session: 618 – Acute Lymphoblastic Leukemia: Biology, Cytogenetics and Molecular Markers in Diagnosis and Prognosis: Poster I
Presenter: Franck Rapaport, Ph.D., computational research leader, Leukemia Center, Memorial Sloan-Kettering Cancer Center
Collaborators: Memorial Sloan-Kettering Cancer Center, Montefiore Medical Center, Mayo Clinic, University of Pennsylvania, Shaare Zedek Medical Center, Northwestern University Feinberg School of Medicine, Weill Cornell Medical College

Poster Display: Sunday, December 6, 2015 from 9:00 a.m.-8:00 p.m. ET
Poster Presentation: Sunday, December 6, 2015 from 6:00-8:00 p.m. ET
Title: Predictive and Prognostic Significance of Comprehensive Genomic Profiling in Patients with Diffuse Large B-cell Lymphoma
Publication Number: 2651
Poster Display Location: Hall A2-A3
Poster Presentation Location: Hall A2-A3
Session: 622 – Non-Hodgkin Lymphoma: Biology, Excluding Therapy: Poster II
Presenter: Jie He, senior manager, computational biology analysis, Foundation Medicine

Poster Display: Sunday, December 6, 2015 from 9:00 a.m.-8:00 p.m. ET
Poster Presentation: Sunday, December 6, 2015 from 6:00-8:00 p.m. ET
Title: Defining the Incidence and Clinical Impact of Genomic Alterations Across Different Histologic Types of Lymphoma Using a Clinically Validated Comprehensive Targeted Sequencing Assay
Publication Number: 2668
Poster Display Location: Hall A2-A3
Poster Presentation Location: Hall A2-A3
Session: 622 – Non-Hodgkin Lymphoma: Biology, Excluding Therapy: Poster III
Presenter: Connie Lee Batlevi, M.D., Ph.D., hematology/oncology fellow, Memorial Sloan-Kettering Cancer Center
Collaborators: Memorial Sloan-Kettering Cancer Center

Poster Display: Monday, December 7, 2015 from 10:00 a.m.-8:00 p.m. ET
Poster Presentation: Monday, December 7, 2015 from 6:00-8:00 p.m. ET
Title: Comprehensive Genomic Profiling (CGP) of Angioimmunoblastic T-cell Lymphoma (AITL) to Prospectively Inform Diagnosis and Clinical Management
Publication Number: 3898
Poster Display Location: Hall A2-A3
Poster Presentation Location: Hall A2-A3
Session: 622 – Non-Hodgkin Lymphoma: Biology, Excluding Therapy: Poster III
Presenter: Tariq Mughal, M.D., vice president, medical affairs, Foundation Medicine
Collaborators: Memorial Sloan-Kettering Cancer Center, Tufts University Medical Center