On March 12, 2015 Epizyme reported that it has reacquired global rights to its EZH2 program, including EPZ-6438, from its partner Eisai Co. Ltd, or Eisai (Press release, Epizyme, MAR 12, 2015, View Source [SID:1234502256]). Under the terms of the agreement, Epizyme will be solely responsible for global clinical development, manufacturing and commercialization in all countries outside of Japan, where Eisai will retain rights. EPZ-6438, a first-in-class inhibitor of EZH2, is currently being evaluated in a Phase 1/2 clinical study for the treatment of B-cell non-Hodgkin lymphoma (NHL) and INI1-deficient solid tumors, such as synovial sarcoma and malignant rhabdoid tumor.

“Over the past seven years, we have been deliberately building Epizyme as an independent, fully integrated oncology company. Obtaining global control of EPZ-6438, a very promising clinical asset, represents an important milestone in the evolution of the Company,” said Robert Gould, Ph.D., President and Chief Executive Officer, Epizyme. “As we began to see the quality and duration of the responses, including two complete responses, in relapsed and refractory NHL and INI1-deficient patients treated with EPZ-6438 as a monotherapy, it became clear to us that having worldwide development and commercialization responsibility for a targeted therapeutic like 6438 would be transformative for Epizyme.”

“With the continued emergence of clinical data on EPZ-6438, it is apparent that this is a therapy with tremendous potential to benefit a variety of patient populations,” said Takashi Owa, Ph.D., Chief Innovation Officer, Eisai Product Creation Systems. “As we re-focus our resources on our later stage programs across therapeutic areas, we believe that Epizyme is well positioned to move EPZ-6438 development forward aggressively. We are pleased that the structure of this agreement allows us to participate in the future success of EPZ-6438.”

Following completion of the transition of EPZ-6438 from Eisai to Epizyme, Epizyme plans to conduct a five-arm Phase 2 study in approximately 150 patients with NHL. This study will evaluate EPZ-6438 in the following patient cohorts:

Diffuse large B-cell lymphoma, germinal center B-cell-like (GCB) type with wild-type EZH2
Diffuse large B-cell lymphoma, GCB type with mutant EZH2
Follicular lymphoma with wild-type EZH2
Follicular lymphoma with mutant EZH2
Diffuse large B-cell lymphoma, non-GCB type

The cohort of patients with diffuse large B-cell non-GCB type is expected to include predominantly patients with wild-type EZH2, since the frequency of EZH2 mutations is approximately 5 percent in this sub-population of diffuse large B-cell lymphoma.

In addition, Epizyme plans to initiate a Phase 2 study in adults with INI1-deficient tumors, including synovial sarcoma, and a Phase 1 study in children with INI-1 deficient tumors, including malignant rhabdoid tumors. Epizyme will also continue the clinical pharmacology studies that are part of the Eisai / Epizyme clinical plan.

“We are pleased to lead the development of EPZ-6438, and look forward to further exploring and defining its clinical activity and safety in a range of hematological and solid tumor indications,” said Peter Ho, M.D., Ph.D., Chief Development Officer, Epizyme.

Terms of the Agreement

Under the terms of the agreement, Epizyme will be responsible for global development, manufacturing and commercialization. Epizyme will fund 100 percent of global development costs, and Eisai will fund 100 percent of Japan-specific development costs.

Epizyme will make a $40 million upfront payment to Eisai, with a total of up to $20 million in potential clinical milestone payments and up to $50 million in potential regulatory milestone payments. Epizyme will pay Eisai a royalty at a percentage in the mid-teens on sales of EPZ-6438 outside of Japan, and Eisai will pay Epizyme a royalty at a percentage in the mid-teens on sales in Japan. Eisai will have a limited right of first negotiation for Asia rights if Epizyme decides to license Asia rights to a third party.