Fast Track Designation Granted to DLBCL SETD2 Inhibitor

An FDA fast track designation has been granted to EZM0414, a first-in-class, oral SETD2 inhibitor for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to a press release by Epizyme, Inc.¹

“The receipt of fast track designation underscores the urgent need for innovative therapies that may significantly improve the lives of patients living with devastating diseases such as DLBCL,” said Shefali Agarwal, MD, executive vice president and chief medical and development officer at Epizyme, in a press release. “Additionally, through the initiation of our Phase 1/1b study, we look forward to evaluating the safety and efficacy of EZM0414 in both DLBCL and multiple myeloma, including high-risk t[4;1] multiple myeloma. Multiple myeloma patients with this high-risk mutation often have a poorer prognosis and are an area of high unmet medical need. We believe the inhibition of SETD2 may play an important role in treating these patients.”

With the designation, the company initiated a phase 1/1b dose-finding study of EZM0414. After the completion of the dose-finding study, efficacy will be evaluated in patients with multiple myeloma, non-multiple myeloma, and DLBCL.

Preclinical studies have found that the agent successfully targets the underlying mechanisms that drive MMSET overexpression. Additionally, it demonstrates that SETD2 is an oncogenic drive in multiple myeloma. Inhibition of SETD2 could help inhibit tumor growth in both t(4;14) and non-t(4;14) multiple myeloma, as seen in xenograft models. In vitro data suggests that the single-agent activity seen with SETD2 inhibitor could be enhanced with the addition of multiple myeloma standard of care agents and other emerging therapies.²

“Today we are excited to announce an important milestone for Epizyme, as we prepare to bring another investigational candidate into the clinic with the initiation of this first-in-human clinical trial of our SETD2 inhibitor, EZM0414,” said Grant Bogle, president and chief executive officer at Epizyme in a press release. “As leaders in pioneering therapies against novel epigenetic targets, bringing EZM0414 to the clinic is an important advancement as we strive to fulfill our vision of making transformative therapies a reality for patients living with cancer.”

_REFERENCES:

_{1.Epizyme receives fast track designation from U.S. FDA and announces initiation of phase 1/1b study of its novel SETD2 inhibitor, EZM0414. News release. Epizyme. November 4, 2021. Accessed November 8, 2021. https://bit.ly/3GVIarL}

_{2.Totman J, et al. Discovery of a selective inhibitor of the SETD2 histone methyltransferase with potent in vitro and in vivo activity in preclinical models of multiple myeloma. Presented at the EHA 2021 Virtual Meeting. June 11, 2021. https://bit.ly/3CWuqdT}