Three years and a trio of targets

CAMBRIDGE, Mass.—Focusing on new epigenetic therapies to fight cancer, biopharmaceutical company Epizyme Inc. and Summit, N.J.-based Celgene Corp. have extended their joint research collaboration for at least three additional years, giving Celgene the option to license histone methyltransferase (HMT) inhibitors being developed by Epizyme against three undisclosed targets. In return, Epizyme gets a $10-million extension fee from Celgene for an option to individually license global rights for two of the targets and for ex-U.S. rights for the third target.

The revised agreement also allows Epizyme to earn total potential milestones of up to $610 million on the three targets, including up to $75 million in development milestones and license fees, $365 million in regulatory milestones and $170 million in sales milestones.

“We believe that the extension of our agreement with Celgene will accelerate our goal of developing new therapies that have the potential to help many patients with epigenetically driven cancers,” Robert Gould, president and CEO of Epizyme, stated in a news release. “Celgene is a leading company in oncology development and commercialization, and we are pleased to continue our partnership on pinometostat and these three exciting novel targets.”

In 2014, Celgene paid $25 million to Epizyme after pinometostat met a proof-of-concept milestone, says Andrew E. Singer, executive vice president and chief financial officer of Epizyme. That deal, which provides Celgene with a license to the drug outside the United States, remains intact after the new agreement with Celgene.

Epizyme is developing pinometostat, 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). Due to these rearrangements, DOT1L is misregulated, resulting in the increased expression of genes causing leukemia.

Epizyme believes that pinometostat was the first HMT inhibitor to enter human clinical development. Epizyme is currently conducting a two-stage Phase 1 study in adult MLL-r patients and, in May 2014, initiated a Phase 1b study of pinometostat in pediatric patients with rearrangements of the MLL gene.

Pinometostat has been granted orphan drug designation for the treatment of acute lymphoblastic leukemia and acute myeloid leukemia by the U.S. Food and Drug Administration and by the European Commission.

Epizyme retains all U.S. rights to pinometostat and has granted Celgene an exclusive license to pinometostat outside of the United States.

“We are not disclosing the specific targets at this time,” Singer tells DDNews of the current deal extension. “What I can say is they are all histone methyltransferases which are of high interest to us and to Celgene, a global leader in oncology.

“We believe this agreement is a validation of Celene’s interest in epigenetics and in Epizyme’s discovery platform. Of note, we are retaining U.S. rights to one of the three targets, which we feel is an important component of our long-term strategy to build an integrated oncology-focused drug discovery, development and commercialization company.”

“Also of note, we regain rights to the rest of our HMT platform, which we believe has the potential to be a driver of Epizyme’s future growth,” Singer adds. “Our long-term goal for this agreement is to advance novel molecules from our platform against these three targets into the clinic.”

Founded in 2007, Cambridge, Mass.-based Epizyme has built a platform used to create small-molecule inhibitors of the 96-member class of HMT enzymes, which are part of the system of gene regulation referred to as epigenetics.

Under the new terms, Celgene may exercise its option with respect to each of the targets at the time of the Investigational New Drug filing for an additional prespecified license payment, while Epizyme is responsible for leading and funding development for each target candidate through Phase 1 clinical trials. After the completion of Phase 1, Celgene may choose to continue its license for a specific target by making an additional prespecified payment.

In the original 2012 agreement, Celgene delivered $90 million up front and as much as $160 million in milestones for a three-year license on some of Epizyme’s programs. The specific focus was on mixed lineage leukemia, a blood cancer that occurs in both children and adults. Epizyme’s treatment, EPZ-5676, or pinometostat, attempts to inhibit the gene DOT1L, which can cause the growth of leukemia cells. Epizyme is conducting clinical trials of EPZ-5676 as a potential personalized therapeutic for pediatric and adult patients with MLL-r acute leukemias.

Epizyme’s other candidate progressing through clinical trials, tazemetostat (or EPZ-6438), attempts to inhibit the EZH2 enzyme, which can cause tumor growth, to treat patients with non-Hodgkin lymphoma or INI1-deficient solid tumors. It is licensed to Japanese pharmaceutical company Eisai and is in Phase 2 clinical trials.

“We have increased investment in tazemetostat development, both as a single agent and in future studies in combination with other agents,” Singer says. “This required reprioritizing our pipeline development plans and reducing operating costs.”

Greg Geissman, director of public relations for Celgene, tells DDNews, “The Epizyme extension is one example of how some of our longer-running, broad partnerships are narrowing focus toward programs where we have seen progress or where we have the most interest. In addition to our in-house research, we look at many potential outside partners, but our goal is to work with organizations that have disruptive science. This, we believe, leads to therapies that make a real impact on diseases, and this is our goal for the agreement with Epizyme.”