CAMBRIDGE, Mass.—Biopharmaceutical company Epizyme Inc. has reacquired global rights to its EZH2 program, including EPZ-6438, from Eisai Co. Ltd. Per the terms of the agreement, Epizyme will assume full responsibility for global clinical development, manufacturing and commercialization in all countries excluding Japan, where Eisai will retain rights. Epizyme will fund 100 percent of global development costs, with Eisai funding the full portion of Japan-specific development costs. Epizyme will pay Eisai $40 million up front, with the potential for up to $20 million in clinical milestone payments and up to $50 million in potential regulatory milestone payments. In addition, Eisai stands to receive a royalty at a percentage in the mid-teens on sales of EPZ-6438 outside of Japan, and will in turn pay Epizyme a royalty at a mid-teen percentage on sales in Japan. Eisai will also have a limited right of first negotiation for rights in Asia should Epizyme decide to license those rights to a third party.
“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. As we refocus our resources on our later-stage programs across therapeutic areas, we believe that Epizyme is well positioned to move EPZ-6438 development forward aggressively,” Dr. Takashi Owa, chief innovation officer for Eisai Product Creation Systems, said in a press release. “We are pleased that the structure of this agreement allows us to participate in the future success of EPZ-6438.”
EPZ-6438 is a first-in-class inhibitor of EZH2. The compound is currently under evaluation 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.
Moving forward, Epizyme intends to conduct a five-arm Phase 2 study of EPZ-6438 in approximately 150 patients with NHL, which will include 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; and diffuse large B-cell lymphoma, non-GCB type. Epizyme is also planning a Phase 2 study in adults with INI1-deficient tumors, including synovial sarcoma, and a Phase 1 study in children with INI1-deficient tumors, including malignant rhabdoid tumors. Epizyme will be continuing the clinical pharmacology studies that are part of the Eisai/Epizyme clinical plan.
“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,” noted Dr. Robert Gould, president and CEO of Epizyme. “As we begin 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.”
Epizyme announced a worldwide strategic partnership with Eisai on March 10, 2011, for the discovery, development and commercialization of therapeutics targeting the epigenetic enzyme EZH2 for the treatment of lymphoma and other cancers in genetically defined patients. That agreement stipulated that Epizyme would receive $6 million in upfront and initial milestone payments, with the potential for more than $200 million in research, development and sales milestones and up to double-digit royalties. Eisai was responsible for funding 100 percent of R&D through human proof of concept, at which point Epizyme had the option of opting into a profit share and co-commercialization arrangement for the United States.
Eisai, Epizyme and Roche Molecular Systems Inc. signed an agreement on Jan. 8, 2013, to collaborate to develop a companion diagnostic to aid Eisai and Epizyme in identifying lymphoma patients, specifically those with genetic mutations of EZH2.
