The U.S. Food and Drug Administration (FDA) granted Fast Track designation to the innovative clinical-stage drug candidate ETX-636, a significant milestone announced today by Ensem Therapeutics, Inc. (ENSEM).

This designation is for the treatment of adult patients battling PIK3CA-mutant, hormone receptor positive (HR+)/human epidermal growth factor negative (HER2-) advanced breast cancer, a highly prevalent subtype where mutations in the PI3Kα pathway are common and associated with a poor prognosis.

ETX-636 stands out as a unique pan mutant-specific allosteric PI3Kα inhibitor and degrader, a design achieved through ENSEM’s proprietary Kinetic Ensemble® platform. Its mechanism of action is highly selective: it optimally fits into a specific allosteric binding site in p110α (the catalytic subunit of PI3Kα) to selectively inhibit multiple activating mutant forms of the protein while completely sparing the wildtype PI3Kα.

This key selectivity is crucial because it is expected to significantly reduce the risk of adverse events like hyperglycemia, which are commonly associated with less-selective, current FDA-approved treatments. Furthermore, ETX-636 possesses a distinct advantage by also inducing proteasome-dependent degradation of the mutant PI3Kα, a feature not observed in other pan-mutant allosteric inhibitors. The company’s CEO, Dr. Shengfang Jin, underscored the urgent, unmet need for safer and more efficacious therapies in this patient population, expressing gratitude that the FDA recognized ETX-636 as a potentially important treatment. The drug is currently being evaluated in a first-in-human Phase 1/2 study to assess its safety, tolerability, pharmacokinetics, and preliminary antitumor activity in patients with PIK3CA-mutant advanced solid tumors, where it will be administered alone or in combination with fulvestrant, an approved selective estrogen receptor degrader. The Fast Track designation is a critical program that will expedite ETX-636’s development and review by allowing for earlier and more frequent communication with the FDA, potentially leading to accelerated approval and faster access to this promising treatment for patients.