CAMBRIDGE, Massachusetts, December 11, 2021– (COMMERCIAL THREAD) – Epizyme, Inc. (Nasdaq: EPZM), a fully integrated, commercial-stage biopharmaceutical company that develops and delivers transformative therapies against novel epigenetic targets, today shares preclinical data and trial design for phase 1 / 1b for EZM0414, the new, first oral inhibitor of SETD2, an investigational agent under development for the treatment of adult patients with relapsed or refractory multiple myeloma (MM) or diffuse large B-cell lymphoma (DLBCL ). The data and design were presented today at the 2021 American Society of Hematology (ASH) annual meeting.
The data presented at the same time in vitro and in vivo preclinical studies (Abstract #1142), demonstrated that targeting SETD2 with EZM0414 resulted in significantly reduced growth of t (4; 14) MM cell lines, as well as non-t (4; 14) MM and DLBCL cell lines. In addition, in in vitro studies, EZM0414 has shown synergy with standard of care for MM and DLBCL and emerging therapies, which supports the potential of studying EZM0414 in combination with current treatments for MM and DLBCL.
“We are delighted to share our preclinical data on EZM0414 with the ASH research community, which demonstrates its anti-tumor activity in multiple myeloma and DLBCL xenograft models, as well as its in vitro combination activity, ”said Dr. Jeffery Kutok, MD, PhD, Scientific Director of Epizyme. “This work increased our understanding of the potential of EZM0414 in malignant B cell tumors and formed the basis of our first studies in humans, starting with our SET-101 Phase 1 / 1b trial.”
Epigenetic mutations and dependencies have been identified in malignant B cell tumors, including MM and DLBCL, providing a therapeutic rationale for epigenetic inhibitors in these types of tumors. Previous data demonstrated that there is a broad sensitivity of MM cell lines to inhibition of SETD2, and in particular, t (4; 14) MM cell lines, which depend on SETD2 due to overexpression of MMSET by the t translocation (4; 14) at high risk.
These preclinical data form the basis of SET-101, the Company’s Phase 1 / 1b clinical study (Abstract #1679), which is designed to assess safety and determine the optimal dose of EZM0414. As part of the trial protocol, after the dose-dosing phase 1 of the trial, the study will be extended to assess EZM0414 in three patient cohorts: t (4; 14) MM, non-t (4 ; 14) MM and DLBCL.
In the phase 1 portion of the study, adult patients with relapsed or refractory MM and DLBCL will be recruited and treated in a Bayesian optimal interval design to assess the safety, tolerability and pharmacokinetics of EZM0414 at six dose levels. Up to 36 patients will be recruited, and at least nine patients will be evaluated for the maximum tolerated dose. At least eight patients, each with t (4; 14) MM, non-t (4; 14) MM or DLBCL will be included. The primary endpoints include the safety and tolerability of EZM0414 and the maximum tolerated dose.
The Phase 1b dose extension portion of the study will consist of three cohorts, t (4; 14) MM, non-t (4; 14) MM and DLBCL, of up to 20 patients each. There will be two interim evaluations when clinical data from the first 10 and 15 patients recruited into each extension cohort become available. Futility assessments will also be done at this time. The final analysis will be performed when all data from the 20 patients in each extension cohort are available. Primary endpoints include recommended phase 2 dose, and secondary endpoints include efficacy and response rates. The trial is currently recruiting patients in the United States and has selected patients for enrollment.
“There is a significant unmet need for new treatment options for patients with multiple myeloma and LDGCB, which are both very aggressive and difficult to treat malignancies,” said Dr. Shefali Agarwal, Executive Vice President and medical and development director at Epizyme. “We are delighted to introduce the first SETD2 inhibitor in the clinic to learn more about its potential in the treatment of these diseases, which is an important milestone for our oncology portfolio. The SET-101 study is open, we are actively screening patients, and we look forward to assaying our first patient and sharing more about EZM0414 as data from the trial becomes available. “
EZM0414 is a potent, selective, oral, small molecule investigational drug that inhibits histone methyltransferase, SETD2, which is involved in oncogenesis. SETD2 methylates histones as well as non-histone proteins, and this activity is involved in several key biological processes, including transcriptional regulation, RNA splicing, and repair of DNA damage. Based on preclinical data on inhibition of SETD2 by EZM0414 in several settings, including high-risk t (4; 14) multiple myeloma (MM) and in other B-cell malignancies such as diffuse lymphoma large B cell (DLBCL), the Company is conducting SET-101, a phase 1 / 1b study of EZM0414, for the treatment of adult patients with relapsed or refractory MM and LDGCB.
About Epizyme, Inc.
Epizyme, Inc. is a fully integrated, commercial-stage biopharmaceutical company committed to its mission to rewrite cancer treatment with novel epigenetic drugs. The Company is focused on creating drugs targeting specific causes of disease that are orally administered, tolerable, easy to take, and based on a deep understanding of the patients who can benefit from them. The Company aspires to change the standards of care for patients and physicians by developing drugs with fundamentally new mechanisms of action. For more information visit www.epizyme.com.
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Any statement in this press release regarding Epizyme, Inc.’s future expectations, plans and prospects and other statements containing the words “anticipate”, “believe”, “estimate”, “expect”, “Intend”, “may”,, “” plan “,” 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 these forward-looking statements due to various important factors, including: whether the commercial sales of TAZVERIK for epithelioid sarcoma and follicular lymphoma in approved indications to be successful; whether tazemetostat will receive marketing authorization for epithelioid sarcoma or follicular lymphoma in other jurisdictions, full authorization in the United States or authorization tion in any other indication; whether the results of preclinical studies, such as the data reported in this press release, or previous clinical studies of the Company’s product candidates will be predictive of future trial results; whether the results of clinical studies will warrant meetings with regulatory authorities, submissions for regulatory approval, or review by government authorities as part of the expedited approval process; whether the company will receive regulatory approvals, including expedited approval, to conduct testing or market products; the impact of the COVID-19 pandemic on the business, results of operations and financial condition of the company; whether the company’s cash resources will be sufficient to finance the company’s foreseeable and unforeseeable operating expenses and its capital expenditure needs; other matters that could affect the availability or commercial success of the tazemetostat; and other factors discussed in the “Risk Factors” section of the Company’s most recent Form 10-K or 10-Q filed with the SEC and in other documents filed from time to time by the Company with the DRY. In addition, the forward-looking statements included in this press release represent the views of the company as of the date hereof and should not be construed as representing the views of the company as of a date subsequent to the date hereof. The company expects subsequent events and developments to cause a change in the outlook of the company. However, although the company may choose to update these forward-looking statements at some time in the future, the company specifically disclaims any obligation to do so.
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Bill Slattery, Jr.