Epizyme Maintains Independence, Advances HMT-Inhibitor Platform

Oncology & Biotech News, April 2014, Volume 8, Issue 4

Epizyme, a Cambridge, Massachusetts-based biotech, opted for independence, with a successful IPO in 2013.

It is a decision that faces every successful startup biotech: sell to Big Pharma or head for IPO waters, and ultimately, independence. Epizyme, a Cambridge, Massachusetts-based biotech, opted for the latter, with a successful IPO in 2013.

From its inception in 2007, Epizyme has entered into several major development deals that have allowed the company to remain independent while advancing its proprietary platform. Epizyme has strategic collaborations with Celgene, Eisai, and GSK, and others.

On the clinical side, Epizyme says on its website that its development strategy is based on “the systematic identification of genetic alterations that create oncogenes, selecting patients where a genetic alteration is found using a companion diagnostic, and then designing small molecule therapeutics to inhibit the oncogene.”

Specifically, Epizyme focuses on developing small molecule inhibitors of histone methyltransferases (HMTs), a class of 96 enzymes. HMTs can become oncogenic through genetic alterations. Based on their individual oncogenic potential, Epizyme is specifically targeting 20 of the 96 HMTs through its proprietary platform.

The company’s two lead candidates are the small molecule inhibitors EPZ-5676 and EPZ-6438. EPZ-5676, which inhibits the HMT DOT1L, is being developed for the treatment of acute leukemias that have a rearrangement of the MLL gene. EPZ-6438 inhibits the HMT EZH2 and is being evaluated for the treatment of non-Hodgkin lymphoma, as well as for INI1-deficient tumors.

In an interview with Oncology & Biotech News, Robert Gould, PhD, chief executive officer of Epizyme, commented on the company’s plan for its lead products this year. “In 2014, we plan to have clinical studies ongoing to assess the proof of concept of our EPZ-5676 and EPZ-6438 therapeutic candidates in five genetically defined cancers. We plan to disclose data from both of these programs in the second half of 2014, including phase I study dose escalation and expansion stage data for EPZ-5676 and phase I dose escalation study data for EPZ-6438.”

Epizyme believes that its phase I EPZ-5676 study (NCT01684150) that includes acute leukemias with MLL rearrangements is the first clinical trial to evaluate an HMT inhibitor. The other proof-of-concept programs Epizyme has planned for EPZ-5676 this year involve pediatric patients with MLL rearrangements resulting from a chromosomal translocation and adult patients with MLL rearrangements due to partial tandem duplication.

In August 2013, the FDA granted orphan drug designation to EPZ-5676. Epizyme is developing the drug through a partnership with Celgene that allows the company to maintain the US rights to market EPZ-5676.

With its EZH2-inhibitor platform, Epizyme has launched a phase I/II clinical trial (NCT01897571) of EPZ-6438 involving patients with advanced solid tumors or relapsed/refractory B-cell lymphomas. A proof-of-concept study for young adult patients with synovial sarcomas is also planned for this year.

Epizyme 2014 Clinical Milestones



2014 Milestones



1. MLL-r adult

  • Phase I dose escalation and MLL-r expansion stage POC data*

  • Epizyme 100% US rights
  • Celgene

2. MLL-r peds

  • Phase Ib POC initiation


  • POC initiation


4. non-Hodgkin lymphoma

  • Phase I dose escalation data*
  • POC initiation**

  • Epizyme 50% US rights
  • Eisai

5. Synovial sarcoma

  • POC initiation**

*Data disclosure in second half of 2014.

**Gated to phase I dose escalation data.

MLL-r indicates mixed lineage leukemia-rearranged; POC, proof of concept;

PTD partial tandem duplication

Epizyme is developing EPZ-6438 through a collaboration with Eisai, which refers to the agent as E7438. The agreement stipulates that Eisai has exclusive worldwide rights to market the product, while retaining for Epizyme the option to co-develop and market EPZ-6438 in the United States. Epizyme is also collaborating with Eisai and Roche on creating a companion diagnostic for identifying patients with EZH2 mutations.