Two down, 94 to go

CAMBRIDGE, Mass.—Epizyme and Celgene International Sàrl, asubsidiary of Celgene Corp., have entered into a strategic partnership todiscover, develop and commercialize personalized therapeutics for patients withgenetically-defined cancers by inhibiting histone methyltransferases (HMTs), animportant epigenetic target class with 96 known members. Epizyme has developedtargets for 20 HMTs to date, states Jason Rhodes, the company's executive vicepresident and chief business officer.

Celgene is its third partnership agreement, Rhodes notes,with GlaxoSmithKline PLC and Eisai preceding Celgene.

Under the terms of the agreement, Celgene receives theexclusive option to license ex-U.S. rights to Epizyme's available HMT inhibitorprograms during an initial three-year period and has the right to extend thisoption period for one year with additional funding. Epizyme retains all U.S. rights to thecollaboration programs and receives a $90 million upfront payment, whichincludes an equity investment. For each HMT inhibitor that Celgene licenses,Epizyme is eligible to earn more than $160 million in milestone payments and upto double-digit royalties on ex-U.S. sales.

Epizyme and Celgene will work jointly to discover anddevelop HMT inhibitors and will co-fund global development of the collaborationprograms. The collaboration includes Epizyme's DOT1L HMT inhibitor program, towhich Celgene licenses the ex-U.S. rights at signing. DOT1L is an oncogenicdriver gene in a subtype of acute leukemias called mixed lineage leukemia(MLL). The DOT1L program is currently in preclinical development and acompanion diagnostic test already exists. Epizyme expects to have human data onthe DOT1L program, as well as its EZH2 target for non-Hodgkin's lymphoma (incollaboration with Eisai), in 12 to 18 months. Celgene was eager to have humanproof of concept early on and the DOT1L program, which is Epizyme's mostadvanced, fit the bill.

Four-year-old Epizyme's strategy is to build a new biopharmacompany based on personalized therapeutics for patients with geneticallydefined cancers. According to Bob Copeland, Epizyme's chief scientific officer,the Celgene partnership is transformational, enabling Epizyme to significantlyexpand the scope of its R&D efforts while retaining U.S. rights where thecompany plans to commercialize its drug candidates independently.

"There were several things about Celgene that wereattractive to us," he says. "Notably, their strong commitment to oncology,personalized medicine and epigenetics. When our CEO Bob Gould visited them, aone-hour presentation became three and a half. We took that as a very goodsign."

Also, Rhodes notes, "Our two companies have complementaryskill sets; ours in discovery and development, and Celgene's in later stages.With this agreement, we gained all the benefits of partnership while retainingU.S. rights and our independence, as well as tremendous access to capital.Through this collaboration, Epizyme gains access to Celgene's leading drugdevelopment resources, enabling us to substantially increase the breadth anddepth of our efforts, while retaining U.S. rights to our pipeline ofpersonalized therapeutics."

"Celgene is a leader in epigenetic therapies for cancerthrough our existing drugs, and continues to focus on delivering new drugs withhigh therapeutic impact in this area," says Dr. Thomas Daniel, president ofresearch at Celgene. "Epizyme's platform, scientific leadership in histonemethyltransferases and leading position on promising HMT targets offer anexciting complementary approach. Our collaboration with Epizyme is a keyelement of our strategy to develop new and innovative therapeutic paradigms."Copeland notes that Epizyme's HMT inhibitor platform isextremely robust and that after DOT1L and EZH2, the other 94 members of theclass will follow in its efforts to discover and develop small-molecule HMTinhibitors. Genetic alterations in HMTs are strongly associated with theunderlying causes of multiple human diseases, including cancer.

Epizyme's patient-driven approach represents the future ofpersonalized therapeutics by creating better medicines for the right patientsmore quickly and at lower cost than traditional approaches, he states.

Celgene International Sàrl, located in Boudry in the Cantonarea of Neuchâtel, Switzerland, is a wholly owned subsidiary of Celgene.Headquartered in Summit, N.J., Celgene is an integrated global pharmaceuticalcompany engaged primarily in the discovery, development and commercializationof innovative therapies for the treatment of cancer and inflammatory diseasesthrough gene and protein regulation.