Forma Therapeutics has initiated a phase I study of FT-1101, with the first dose administration in patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome. FT-1101 is an oral, structurally distinct and potent pan-inhibitor of the BET (bromodomain and extra-terminal) epigenetic protein family.

“The BET protein family represents an attractive group of therapeutic targets for a variety of liquid and solid tumors, as inhibition of these epigenetic binding proteins allows for selective effects on gene expression. FT-1101 is a novel, oral small molecule targeted against all four BET family members (BRD2, BRD3, BRD4, BRDT),” said John Hohneker, M.D., EVP and head of R&D, Forma Therapeutics. “The launch of this study is an important step for our team, and we are eager to begin the selection of preferred dosing schedules and potential patient populations in order to optimize activity and tolerability of this novel medicine.”

Small molecule inhibition of BET results in down-regulation of the critical oncogene MYC, a master regulator of diverse cell functions critical for cell growth and survival in many cancers. At tolerated doses in human tumor xenograft mouse models, FT-1101 has demonstrated significant anti-tumor activity including tumor regressions.

FT-1101 is part of Forma’s second global strategic collaboration with Celgene, announced in April 2014. Celgene has obtained an exclusive EU license for FT-1101 in exchange for an undisclosed payment to FORMA. Forma will advance the FT-1101 program through phase I, and Celgene will be responsible to fund and execute further global clinical development.

“I am impressed with the inhibition profile and differentiated preclinical activity of FT-1101, and we aim to move quickly to define the safety, tolerability and initial activity of this novel BET inhibitor in acute leukemias and myelodysplastic syndrome,” said Guillermo Garcia-Manero, M.D., lead clinical investigator for FT-1101 at The University of Texas MD Anderson Cancer Center, Houston, and professor, department of leukemia, division of cancer medicine.

The phase I, multicenter, open-label, dose escalation clinical trial is designed to assess the safety and tolerability of FT-1101 capsules as a single agent. FT-1101 will be administered orally on a once weekly dosing schedule in a 28-day cycle. The study will enroll patients with relapsed refractory AML and high risk myelodysplastic syndrome. Key objectives in the study include determination of a maximum tolerated dose, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of FT-1101.

FORMA is headquartered in Watertown, Massachusetts, near the epicenter of the Cambridge Life Sciences cluster, with additional chemistry operations in Branford, Connecticut.