Epizyme Reports Positive Interim Data from Phase 2 Trial for Tazemetostat in Relapsed or Refractory Follicular Lymphoma and DLBCL Patients

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| Source: Epizyme, Inc.

Data Presented During Plenary Session at International Conference on Malignant Lymphoma

Conference Call to be Held Today at 10:30 a.m. ET

CAMBRIDGE, Mass., June 14, 2017 (GLOBE NEWSWIRE) -- Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, today announced positive interim efficacy data from the company’s ongoing Phase 2 clinical trial of tazemetostat, a first-in-class, oral EZH2 inhibitor, as a single-agent treatment for relapsed or refractory patients with follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) grouped by EZH2 mutational status. The data were presented today during a plenary session at the International Conference on Malignant Lymphoma (ICML), which is being held June 14-17, 2017 in Lugano, Switzerland. In addition, data from a 62-gene panel biomarker study of tazemetostat in patients with various subtypes of non-Hodgkin lymphoma will be presented during a poster session at the conference.

Interim data as of June 1, 2017 show that tazemetostat treatment resulted in a clinically meaningful benefit in patients with FL. The subset of FL patients with EZH2 activating mutations have a 92 percent objective response rate (ORR). Patients with FL with EZH2 wild-type have an ORR of 26 percent and 22 percent of patients with stable disease are still on study. Promising activity was also observed in DLBCL patients with EZH2 mutations, which includes recently enrolled patients, with an ORR of 29 percent. As the size of the mutation study groups increase and patients remain on study, Epizyme expects the data will continue to evolve. In addition, tazemetostat continues to demonstrate a favorable safety profile across all patient populations in this study.

“I believe that tazemetostat may play a significant role in disease management for my patients, and am particularly excited by the impact observed in patients with follicular lymphoma,” said Franck Morschhauser, M.D., Ph.D., Centre Hospitalier Régional Universitaire de Lille, France, and lead investigator of the Phase 2 study. “I am also encouraged by the level of activity in DLBCL patients with EZH2 mutations, especially in light of the bleak prognosis associated with advanced disease. Tazemetostat has demonstrated a uniquely tolerable safety profile, and I look forward to further exploring its full benefit in patients with relapsed or refractory FL and DLBCL as the data mature.”

“These interim data findings represent an important step forward for our tazemetostat program, with anti-tumor activity observed across all groups of the study,” said Rob Bazemore, chief executive officer of Epizyme. “The activity we have observed in patients with an EZH2 mutation exceeds what we have seen so far with wild-type EZH2, consistent with our scientific hypothesis, and we are encouraged by both the objective responses and durability of responses in FL and DLBCL. Our focus is on continuing to increase enrollment of patients with an EZH2 mutation, and engaging with FDA in the second half of the year to determine potential registration paths to bring tazemetostat to patients as quickly as we can.”

Follicular Lymphoma Efficacy Data
FL, an indolent form of non-Hodgkin lymphoma (NHL), is considered to be incurable with existing treatments and is characterized by cycles of relapse that become increasingly difficult to treat with each disease progression. Approximately 25,000 patients in the U.S. and major European countries are diagnosed with FL every year1, of which an estimated 15 to 20 percent have an EZH2 mutation. There are no approved treatments indicated for patients with FL with an EZH2 mutation. In April 2017, Epizyme was granted Fast Track designation for FL regardless of EZH2 mutational status.

As of June 1, 2017, Epizyme enrolled 19 FL patients with EZH2 activating mutations in the Phase 2 trial, of which 13 are evaluable for efficacy. Enrollment of FL patients with EZH2 wild-type was completed in late 2016 with a total of 54 patients, all of which are evaluable for efficacy. More than 75 percent of evaluable FL patients had three or more prior treatments, and approximately 50 percent of patients in each group were refractory to their last prior therapy.

Key interim efficacy findings are as follows:

 FL with EZH2 MTFL with EZH2 WT
Evaluable for efficacy on June 1, 2017n =13n =54
Objective Response Rate (CR + PR)12 (92%)14 (26%)
  Complete Response (CR)1 (8%)3 (6%)
  Partial Response (PR)11 (85%)11 (20%)
  Stable Disease (SD)1 (8%)23 (43%)
   SD study drug ongoing1 (8%)12 (22%)
  Progressive Disease013 (24%)
  No Data, Unknown (UNK)04 (7%)
Time to first Response (weeks)
  median (range)
11.9
(6.9 – 35.9)
15.2
(8.1 - 32.1)

The activity of tazemetostat across FL patients is encouraging, and when combined with the well-tolerated safety profile, supports its potential utility as both as monotherapy and a combination agent. Combination treatment has become the evolving standard-of-care for FL, and Epizyme plans to begin investigating tazemetostat as a combination agent in FL this year.  

Diffuse Large B-Cell Lymphoma Efficacy Data
DLBCL is an aggressive form of NHL that once diagnosed, typically requires immediate treatment. Approximately 45,000 patients are diagnosed with DLBCL in the U.S. and major European countries every year2. Among patients with germinal center DLBCL, an estimated 15 to 20 percent have an EZH2 mutation. Forty to 50 percent of patients will relapse on their first-line treatment, which is most commonly the chemotherapy regimen R-CHOP, and there are few treatment options for patients who relapse or become refractory to chemotherapy. In November 2016, Epizyme was granted Fast Track designation for DLBCL with EZH2 mutations.

As of June 1, 2017, Epizyme had enrolled 22 DLBCL patients with EZH2 mutations, and efficacy was assessed on 17 patients. Enrollment of DLBCL patients with EZH2 wild-type (germinal center and non-germinal center) was completed in early 2017 with 120 patients, of which 119 were evaluable for efficacy. Patients with DLBCL with EZH2 activating mutations represent the most advanced and severely ill patients in the study, with 82 percent having been previously treated with at least three therapeutic regimens and refractory to their last treatment.

Key interim efficacy findings are as follows:

 DLBCL EZH2 MTDLBCL EZH2 WT
Evaluable for efficacy on June 1, 2017n = 17n = 119
Objective Response Rate (CR + PR)5 (29%)18 (15%)
  Complete Response (CR)010 (8%)
  Partial Response (PR)5 (29%)8 (7%)
  Stable Disease (SD)6 (35%)22 (18%)
   SD study drug ongoing1 (6%)4 (3%)
  Progressive Disease6 (35%)60 (50%)
  No Data, Unknown (UNK)019 (16%)
Time to first Response (weeks)
  median (range)
8.3
(4.6 – 48.1)
8.5
(5.3 – 24.7)

Epizyme believes that activity is likely to be enhanced for wild-type disease through combination treatment. The company has a robust combination program underway in DLBCL evaluating tazemetostat in an immuno-oncology combination with atezolizumab and a steroid combination with prednisolone. In addition, tazemetostat is being evaluated in the front-line setting in combination with R-CHOP in newly diagnosed, high-risk DLBCL patients.

Tazemetostat Safety Profile
Safety data from patients in this Phase 2 trial (n=210), as of the data cutoff, demonstrate a favorable tolerability profile, consistent with the experience observed in a nearly 400-patient safety database from tazemetostat clinical trials to date. Across all cohorts of this trial, dose reductions and discontinuations due to treatment-related adverse events are low, at only three and two percent, respectively.

The majority of treatment-emergent adverse events are grade 1 or 2, with only 18 percent of grade 3 or higher being considered treatment-related. Treatment-emergent adverse events, regardless of attribution and affecting more than five percent of patients, are nausea (20%); thrombocytopenia (19%); anemia (16%); cough (14%); fatigue (12%); diarrhea (11%); asthenia, neutropenia, pyrexia and vomiting (10% each); bronchitis (7%); and constipation, decreased appetite, upper respiratory infection, abdominal pain, headache and urinary tract infection (6% each).

Poster Presentation Information
Data from a 62-gene panel biomarker study of tazemetostat in patients with various subtypes of NHL will also be presented in a poster by Stephen Blakemore Ph.D., titled “Preliminary evidence of a molecular predictor of tazemetostat response, beyond EZH2 mutation, in NHL patients via characterization of archive tumor and circulating tumor DNA” on June 14, 2017 (Poster Board No.: 154).

The data in the poster detail both potential positive and negative predictors of response to tazemetostat. In the case of positive predictors, both EZH2 and MYD88 are mutations that appear to enhance patients’ sensitivity to tazemetostat. The company has also detected EZH2 mutations by circulating tumor DNA in patient serum, indicating the potential future use of a tube of blood for patient identification of EZH2 mutations rather than testing patient’s archival tumor samples.

Conference Call Information
Epizyme will host a conference call and audio webcast today at 10:30 a.m. ET. To participate in the conference call, please dial (877) 844-6886 (domestic) or (970) 315-0315 (international) and refer to conference ID 15855261. The webcast, and accompanying slides for the call, will be accessible under "Events and Presentations" in the Investor Relations section of the Company's website at http://www.epizyme.com/.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied in ongoing Phase 2 programs in both follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) forms of non-Hodgkin lymphoma; certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors; and mesothelioma, as well as in combination studies in DLBCL. Tazemetostat has been granted Fast Track designation by the U.S. Food and Drug Administration for both relapsed/refractory follicular lymphoma and DLBCL with EZH2 activating mutations, as well as Orphan Drug designation for malignant rhabdoid tumors.

About Epizyme, Inc.
Epizyme, Inc. is a clinical-stage biopharmaceutical company committed to rewriting cancer treatment through novel epigenetic medicines. Epizyme is broadly developing its lead product candidate, tazemetostat, a first-in-class EZH2 inhibitor, with studies underway in both solid tumors and hematological malignancies, as a monotherapy and combination therapy and in relapsed and front-line disease. Using the Company’s proprietary platform, Epizyme has pioneered the identification and development of small molecule inhibitors of chromatin modifying proteins (CMPs), such as tazemetostat. 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, which can allow cancer cells to grow and proliferate. By focusing on the genetic drivers of cancers, Epizyme's science seeks to match targeted medicines with the specific patients that need it. For more information, visit www.epizyme.com and connect with us on Twitter at @EpizymeRx.

Cautionary Note on Forward-Looking Statements
Any statements in this press release about future expectations, plans and prospects for Epizyme, Inc. 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 1995. 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 and in the availability and timing of data from ongoing clinical studies; whether results from preclinical studies or earlier clinical studies will be predictive of the results of future studies; whether interim data from clinical studies such as the data reported in this presentation will be indicative of the final results of the study; whether results from clinical studies will warrant meetings with regulatory authorities or submissions for regulatory approval; whether submissions for regulatory approval will be made when anticipated or at all and whether these submissions will be reviewed under the accelerated approval framework; whether the Company will receive will receive regulatory approvals to conduct trials or to market products; whether the Company's cash resources will be sufficient to fund the Company's foreseeable and unforeseeable operating expenses and capital expenditure requirements; other matters that could affect the availability or commercial potential of the Company's therapeutic candidates; and other factors discussed in the "Risk Factors" section of the Company's most recent Form 10-Q filed with the SEC and in the Company's other filings from time to time with the SEC. In addition, the forward-looking statements included in this press release represent the Company's views as of the date hereof and should not be relied upon as representing the Company's views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.

1 Decision Resources, 2017

2 Decision Resources, 2017

Contacts:
Cheya Pope, Epizyme, Inc.
media@epizyme.com
617-229-7561

Monique Allaire, THRUST IR
monique@thrustir.com 
(617) 895-9511