WATERTOWN, Mass.–(BUSINESS WIRE)–FORMA Therapeutics, Inc., a clinical stage biopharmaceutical company focused on rare hematologic diseases and cancers, today announced the online publication of the structure-based design and discovery of its most advanced clinical asset, olutasidenib, in the Journal of Medicinal Chemistry. The paper details structure-based approaches to design a potent mutant IDH1 inhibitor with pharmacokinetic properties that include blood-brain barrier permeability. The paper is also expected to be published in the Feb. 27 print edition of the journal.
“This work highlights FORMA’s efforts to discover and develop highly selective, potent molecules to create breakthrough medicines for patients with rare hematologic diseases and cancers,” said Patrick Kelly, M.D., chief medical officer of FORMA Therapeutics. “Olutasidenib is a viable oral clinical compound that potently and selectively inhibits 2-hydroxyglutarate production, and these results lead us to believe it will be able to restore normal cellular differentiation in IDH1-mutated cancers.”
FORMA discovered olutasidenib through the company’s innovative drug discovery platform, which combines high throughput screening with DNA-encoded library screens for lead identification and then utilizes a highly technology-leveraged parallel optimization process to develop lead candidates. The program has since been moved into the clinic to allow further investigation of its demonstrated potential. Additional information about proof of mechanism and differentiating clinical data for FORMA’s program in glioma was presented at the 2019 Society for Neuro-Oncology Conference.
“We are extremely proud of the technical and scientific prowess our team has demonstrated by yielding a diverse pipeline of novel or next-generation oral medicines for FORMA’s own continued development and development by licensees of our molecules,” Dr. Kelly added.
FORMA Therapeutics’ most advanced clinical asset, olutasidenib, is designed to be a potent and selective next generation inhibitor of mutated isocitrate dehydrogenase 1 (IDH1m) to treat patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), as well as patients with glioma and other solid tumors with an IDH1 mutation. IDH1 is a natural enzyme that is part of the normal metabolism in all cells; when mutated, its activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 7-14% of patients with AML, 3-4% of patients with MDS, and more than 70% of patients with gliomas. In AML, hypermethylation driven by IDH mutations inhibits normal differentiation of progenitor cells leading to accumulation of immature blasts. Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed disease remain an unmet need. In MDS, often a precursor to AML, epigenetic changes from aberrant DNA methylation contribute to the formation of blast cells and the progression of MDS to AML.
FORMA is evaluating olutasidenib as a single agent and in combination with azacitidine in a pivotal study in patients with relapsed/refractory acute myeloid leukemia (R/R AML) with an IDH1 mutation. Additional patient populations with IDH1m hematological oncology disease or advanced solid tumors and gliomas are also being evaluated.
About FORMA Therapeutics
FORMA Therapeutics is focused on the discovery, development and commercialization of transformative medicines for patients with rare hematologic diseases and cancers. A fully integrated biopharmaceutical company, FORMA’s validated, proprietary R&D engine combines deep biology insight, chemistry expertise and clinical development capabilities to create differentiated drug candidates with best-in-class or first-in-class potential. FORMA has delivered high-value clinical candidates to its partners and generated a broad proprietary portfolio of programs, ranging from preclinical to pivotal-stage, with the potential to provide profound patient benefit. For more information, please visit the company website at www.formatherapeutics.com or follow us on Twitter @FORMAInc and LinkedIn.