WALTHAM, Mass.– Ensem Therapeutics, Inc. (ENSEM) announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ETX-636, the company’s clinical-stage pan mutant-specific allosteric PI3Kα inhibitor and degrader, for the treatment of adult patients with PIK3CA-mutant, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer.
ETX-636 was developed using ENSEM’s proprietary Kinetic Ensemble® platform and is designed to fit into a specific allosteric binding site in p110α, the catalytic subunit of PI3Kα. The drug selectively inhibits multiple activating mutant forms of PI3Kα while sparing wildtype PI3Kα, reducing the risk of hyperglycemia and other wildtype-related side effects. In addition, ETX-636 leads to proteasome-dependent degradation of mutant PI3Kα while leaving the wildtype protein intact, a capability not seen with other pan-mutant allosteric inhibitors.
PIK3CA mutations are a major driver of tumor growth in several cancers, including breast cancer. In HR+/HER2- breast cancer—accounting for roughly 70 percent of all breast cancer cases—PIK3CA mutations occur in up to 40 percent of patients.
“Patients with advanced HR+/HER2- breast cancer harboring PIK3CA mutations have poor prognosis, and there is an unmet need for therapies targeting this population that are safer and more efficacious than the current FDA-approved non-mutant selective treatments,” said Dr. Shengfang Jin, CEO and Co-Founder of Ensem Therapeutics. “We are appreciative that the FDA has recognized ETX-636 as a potentially important treatment for this indication and we remain laser-focused on demonstrating its benefit to patients in our current clinical trials.”
ETX-636 is currently being evaluated in a first-in-human Phase 1/2 study to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity in participants with advanced solid tumors carrying a PIK3CA mutation. The study (NCT06993844) will test ETX-636 as a monotherapy and in combination with fulvestrant, an estrogen receptor degrader approved for HR+/HER2- advanced breast cancer.
Fast Track designation is intended to expedite the development and review of therapies that treat serious conditions with significant unmet medical need. It allows for increased communication with the FDA, rolling review of applications, and eligibility for priority review and accelerated approval.
