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Agios announces new data from ongoing Phase 1 trial of AG-221 showing robust clinical activity in patients with advanced hematologic malignancies

, , a leader in the fields of cancer metabolism and rare genetic disorders of metabolism, has announced new data from the ongoing Phase 1 dose escalation study of AG-221 as a single agent in patients with IDH2-mutant positive advanced . With additional patient enrollment and longer follow-up, the data continue to show a favorable safety profile as well as durable clinical activity for AG-221, with an overall response rate of 56 percent (25 of 45 ) in advanced . Eytan Stein, M.D., lead investigator and attending physician in the leukemia service at , will present the data in an oral presentation today at the 56th Annual American Society of Hematology (ASH) Annual Meeting and Exposition being held in San Francisco. AG-221 is a first-in-class, oral, selective, potent inhibitor of the mutant IDH2 (isocitrate dehydrogenase-2) enzyme being developed in collaboration with Celgene.

“The durable responses observed for AG-221 with minimal toxicity being reported are impressive in this advanced disease setting,” said Dr. Stein. “These findings build upon those presented throughout the year. In addition, they continue to provide evidence that AG-221 can inhibit the IDH2 mutant protein, stop production of the oncometabolite, 2-HG, and allow for to become mature, functioning blood cells. This approach is different from traditional chemotherapy that attempts to non-selectively kill . I believe AG-221′s unique mechanism targeting a specific mutation is the way of the future and represents a highly specific oral therapy that may transform the treatment of a devastating group of blood cancers.”

As of the data cut-off on October 1, 2014, the ongoing Phase 1 study of AG-221 had enrolled 73 patients, with a documented IDH2 mutation, in a broad range of advanced hematologic malignancies. Patients enrolled included those with relapsed or refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and untreated AML who decline intensive chemotherapy. At the time of the data cut- off, 45 patients were evaluable for an analysis of clinical activity. Twelve patients had initiated therapy too recently and were therefore not evaluable and 16 patients had discontinued without an evaluable day 28 assessment. The data showed that 25 out of 45 evaluable patients achieved

investigator-assessed objective responses, including six complete remissions, nine complete remissions with various degrees of hematologic recovery and ten partial remissions. An estimated 90 percent of patients who responded had responses lasting for at least three months, with durations on AG-221 for as long as eight months and ongoing. For patients who achieved a complete remission, their cancer did not progress while on therapy. AG-221 was well tolerated and the overall safety profile observed was consistent with previously reported data. A maximum tolerated dose (MTD) had not been reached. These data form the basis for the planned initiation of a global registration program in 2015.