WALTHAM, Mass.– Ensem Therapeutics has started dosing patients in a Phase 1/2 clinical trial of ETX-636, an experimental treatment aimed at cancers with PI3Kα mutations, including a subset of advanced breast cancers.
ETX-636 is designed to selectively target and degrade mutant forms of PI3Kα — a protein often altered in cancer — while avoiding the normal, or wildtype, version. This selectivity could make the drug more tolerable for patients than existing treatments, which often affect both mutant and normal PI3Kα and lead to side effects such as high blood sugar.
“Starting this trial is an important step forward,” said Dr. Ron Peck, Ensem’s Chief Medical Officer. “We believe ETX-636’s selectivity could offer a better safety profile while still being effective against tumors.”
The study will test ETX-636 in people with advanced solid tumors that carry PI3Kα mutations. The first dose was administered at START San Antonio under the direction of Dr. Amita Patnaik. The drug will be evaluated on its own and in combination with fulvestrant, a hormone therapy commonly used in breast cancer treatment.
ETX-636 is Ensem’s second oral drug candidate to enter clinical trials. CEO Dr. Shengfang Jin said the company plans to advance more programs into clinical development in 2026.
Preclinical studies suggest ETX-636 may block the activity of mutant PI3Kα and also trigger its degradation — a two-pronged approach that showed tumor shrinkage in lab models without disrupting blood sugar levels.
The trial is registered under NCT06993844.
