Epizyme Reports Publication of Preliminary Findings from Phase 1 Study of DOT1L Inhibitor EPZ-5676 in ASH Annual Meeting Abstract

  • Thirty-six patients were evaluable for safety and 28 patients were evaluable for efficacy across six dosing cohorts (12, 24, 36, 54, 80 and 90 mg/m2/day) as of July 15th data cut-off
  • Adverse events were predominantly Grade 1 or Grade 2 in severity
  • Complete responses seen in two patients with MLL-r; same two patients from the 54 mg/m2 cohort whose objective responses were reported by Epizyme in January 2014 as proof of concept
  • Additional findings of biological activity were observed in several patients
  • Preliminary results will be published in abstract form today on ASH website; updated data to be presented at ASH meeting on December 8th
  • Epizyme will discuss abstract data during its third quarter earnings call today at 8:00 a.m. ET
ASH 2014

CAMBRIDGE, Mass.--()--Epizyme, Inc., a clinical stage biopharmaceutical company creating innovative personalized therapeutics for patients with genetically defined cancers, today announced the publication on the website of the American Society of Hematology (ASH) of an abstract entitled “The DOT1L Inhibitor EPZ-5676: Safety and Activity in Relapsed/Refractory Patients with MLL-Rearranged Leukemia”. The abstract contains preliminary data from the Phase 1 trial of EPZ-5676, a potent and selective inhibitor of the DOT1L histone methyltransferase (HMT). EPZ-5676 is being developed for the treatment of acute leukemia with alterations in the MLL gene (MLL-r) or partial tandem duplications within MLL (MLL-PTD). The Company plans to present updated data from the trial at the 56th annual meeting of ASH in San Francisco, Calif. on December 8th. The Company will discuss results from the abstract, along with third quarter financial results, during its quarterly call, scheduled for 8:00 a.m. ET today.

“We are pleased with the safety of EPZ-5676 in this study. Within this extensively pre-treated patient population, we are also pleased to see two complete responses in the 54 mg/m2 cohort and additional indications of biological activity in other patients”

The data in the abstract show that EPZ-5676 was safe and well tolerated in the 36 patients who were evaluable for safety across all dosing cohorts as of the abstract data cut-off on July 15th. Adverse events were predominantly Grade 1 or Grade 2 in severity, and there were only two patients who discontinued treatment due to possibly drug-related adverse events. Of the 28 patients who were evaluable for efficacy, two MLL-r patients in the 54 mg/m2 dosing cohort achieved complete responses, and biological activity was seen in several patients who experienced resolution of cutaneous leukemia or leukemia cell differentiation effects. The patients who achieved complete responses were the same two patients whose objective responses were reported by Epizyme in January 2014.

“We are pleased with the safety of EPZ-5676 in this study. Within this extensively pre-treated patient population, we are also pleased to see two complete responses in the 54 mg/m2 cohort and additional indications of biological activity in other patients,” said Peter Ho, M.D., Ph.D., Chief Development Officer, Epizyme. “We plan to expand the number of patients in the 54 mg/m2 cohort to explore further the activity of treatment with EPZ-5676 at this dose.”

“Epizyme continues to be a leader in the field of HMT inhibitors. EPZ-5676, along with EPZ-6438, our inhibitor of the HMT EZH2, are the first two HMT inhibitors to advance into clinical testing,” said Robert Gould, Ph.D., President and Chief Executive Officer, Epizyme. “We look forward to presenting a detailed update on EPZ-6438 at the EORTC-NCI-AACR Symposium on November 20th, including more complete dose escalation data from the Phase 1 study. This will be followed on December 8th by our ASH presentations, which will include the updated clinical data presentation on EPZ-5676, as well as an oral presentation of pre-clinical data on one of our pipeline molecules, a first-in-class PRMT5 inhibitor, and a poster on PK modeling for the EPZ-5676 pediatric study.”

The DOT1L Inhibitor EPZ-5676: Safety and Activity in Relapsed/Refractory Patients with MLL-Rearranged Leukemia (ASH Abstract #387)

The Phase 1 clinical trial of EPZ-5676 is an open label, multi-center trial that has two stages. The first is a dose escalation stage in adult patients with advanced hematologic malignancies, including MLL-r patients. The second is an expansion stage that is only enrolling MLL-r and MLL-PTD patients. Study objectives included safety and tolerability, dose identification, pharmacokinetics, pharmacodynamics and early evidence of anti-leukemic activity.

At the data cut-off for the ASH abstract submission, 36 patients had received at least one dose of EPZ-5676 via continuous intravenous infusion and were evaluable for safety. Thirty-one of these patients had acute myeloid leukemia (AML; 21 MLL-r, 5 MLL-PTD), four had acute lymphocytic leukemia (ALL; 3 MLL-r) and one had a myeloproliferative disorder (MPD; MLL-r). The median age at time of enrollment was 53 years (range: 20 to 81 years) and the median number of prior systemic therapies was two (range: 1 to 6 therapies). Fourteen patients had a prior allogeneic stem cell transplant.

Adverse events reported in more than 15% of patients, independent of relationship to study drug, were largely Grade 1 or Grade 2 in severity and included anemia, fever/neutropenia, thrombocytopenia, constipation, diarrhea, nausea, chills, fatigue, mucosal inflammation, peripheral edema, hypomagnesemia, dyspnea and sepsis. Adverse events assessed by investigators to be drug related were leukocytosis, nausea and hypomagnesemia, and PR prolongation. The maximum tolerated dose has not been reached. Two patients discontinued treatment due to adverse reactions that were potentially study drug related. There were no deaths attributed to study drug treatment.

Among 23 patients with MLL-r or MLL-PTD who had at least one post-baseline evaluation, one MLL-r patient achieved a morphologic complete response and one MLL-r patient achieved a cytogenetic complete response. Several patients experienced resolution of leukemia cutis or a treatment-related increase in neutrophils (PMN) and/or monocytes, consistent with a differentiation effect. The identification of the MLL-r by split signal FISH in mature PMN suggests a differentiation effect on the leukemic clone.

Pharmacokinetic exposures were dose proportional, and steady state plasma concentrations were reached on the first day of dosing. The preliminary pharmacodynamic data show reduced histone H3K79 methylation from baseline in marrow and peripheral blood mononuclear cells after 15 days of treatment at doses above 36 mg/m2/day. H3K79 rebounded towards baseline levels by day 28 in patients who received treatment for 21 of 28 days, whereas among patients who received treatment for 28 of 28 days, methyl-mark inhibition was maintained throughout the cycle.

About EPZ-5676

Epizyme is developing EPZ-5676, 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) or a partial tandem duplication (MLL-PTD). Due to these rearrangements, DOT1L is misregulated, resulting in the increased expression of genes causing leukemia.

Epizyme believes that EPZ-5676 was the first HMT inhibitor to enter human clinical development. Epizyme is currently conducting a two-stage Phase 1 study in adult MLL-r and MLL-PTD patients and, in May 2014, initiated a Phase 1 study of EPZ-5676 in pediatric patients with rearrangements of the MLL gene. The adult dose escalation stage has completed enrollment, and the adult MLL-r and MLL-PTD expansion stage is enrolling patients. Additional information about these ongoing Phase 1 studies can be found here: http://clinicaltrials.gov/show/NCT01684150

EPZ-5676 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 EPZ-5676 and has granted Celgene an exclusive license to EPZ- 5676 outside of the U.S. Additional information about Epizyme's partnerships is available here: www.epizyme.com/about-us/partnerships/.

About Epizyme, Inc.

Epizyme, Inc. is a clinical stage biopharmaceutical company creating personalized therapeutics for patients with genetically defined cancers. Epizyme has built a proprietary product platform that the Company uses to create small molecule inhibitors of a 96-member class of enzymes known as histone methyltransferases, or HMTs. HMTs 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 HMTs, 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 a personalized approach to cancer treatment.

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 or expansion of ongoing clinical studies, whether interim or preliminary results from a clinical trial such as the results reported in this release will be predictive of the final results of the trial or results of early clinical studies will be indicative of the results of future trials; expectations for regulatory approvals, availability of funding sufficient for 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 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 in August 2014. In addition, the forward-looking statements included in this press release represent the Company's views as of 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. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date hereof.

Contacts

Media/Investors:
Epizyme, Inc.
Manisha Pai, 617-229-7560
mpai@epizyme.com

Epizyme, Inc.