Agios Pharmaceuticals Announces Initiation of a Phase 1/2 Clinical Trial of AG-221 in Patients with Advanced Solid Tumors with an IDH2 Mutation
Preclinical evidence shows that mutant IDH2 enzyme, the target of AG-221, produces 2-hydroxyglutarate (2HG), which blocks the normal maturation of progenitor cells. In solid tumor cells expressing the IDH2 mutation, AG-221 inhibited the production of 2HG, which has the potential to affect differentiation and cell proliferation in patients with solid tumors. In addition, AG-221 has demonstrated an acceptable safety profile and evidence of antitumor activity in the ongoing Phase I trial of AG-221 in patients with advanced hematologic malignancies that carry an IDH2 mutation.
About the Phase 1/2 Trial
The Phase 1/2 multicenter, open-label, dose-escalation clinical trial of AG-221, which is being conducted by Agios, is designed to assess the clinical activity, safety and tolerability of AG-221 among patients who have an IDH2-mutant advanced solid tumor. AG-221 will be given as a single agent and will be administered orally at an initial dose of 100 mg once daily, in 28-day cycles. Key objectives of the trial include describing the dose-limiting toxicities and determining the maximum tolerated dose, evaluating the pharmacokinetic and pharmacodynamics, and characterizing the clinical activity of AG-221. The Phase 1/2 trial is expected to include a dose expansion phase where three cohorts of patients with gliomas, AITL and other solid tumors that are IDH2 mutant-positive will receive AG-221 to further evaluate safety, tolerability and clinical activity.
AG-221 and IDH2
IDH1 and IDH2 are metabolic enzymes that are mutated in a wide range of hematologic and solid tumor malignancies, including AML. Normally, IDH enzymes help to break down nutrients and generate energy for cells. When mutated, IDH creates a molecule that alters the cells' genetic programming, and instead of maturing, the cells remain primitive and proliferate quickly. Agios believes that inhibition of these mutated proteins may lead to clinical benefit for the subset of cancer patients whose tumors carry them. AG-221 was developed by Agios as a selective, potent inhibitor of the mutated IDH2 protein. While most cancer treatments attempt to destroy the cancerous cells, AG-221 uniquely attacks its target – mutated IDH2 – and aids the maturation of the cells into functioning blood cells. AG-221 has received orphan drug designation for AML and fast track designation for patients with IDH2-mutant AML.
About Agios/Celgene Collaboration
AG-221 is a part of Agios' global strategic collaboration with
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the potential of IDH2 mutations as therapeutic targets; the potential benefits of Agios' drug candidate AG-221 targeting IDH2 mutations; its plans and timelines for the clinical development of AG-221; and the benefit of its strategic plans and focus. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "could," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios' current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios' product candidates will successfully continue. There can be no guarantee that any positive developments in Agios' business will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other important factors, including: Agios' results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S.
Agios Pharmaceuticals, Inc. Lora Pike, 617-649-8608 Senior Director, Investor Relations and Public Relations firstname.lastname@example.org