ETX-636 / Ensem Therap - LARVOL DELTA

Ensem Therapeutics Doses First Patient in China in ETX-636 Global Phase 1/2 Study (Businesswire) - "The rapid study initiation of ETX-636 in China follows the November 19th approval of the Investigational New Drug (IND) application by China’s National Medical Products Administration (NMPA)....The ongoing first-in-human, global Phase 1/2 study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of ETX-636 in patients with advanced solid tumors harboring PI3Kα mutations (NCT06993844)....Dose escalation in the United States is progressing as planned, and ETX-636 has been well tolerated to date, with no observed hyperglycemia or dose-limiting toxicities. ENSEM expects to disclose preliminary clinical data supporting proof of concept in the second half of 2026."

P1/2 data • Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Ensem Therapeutics Announces ETX-636 Granted Fast Track Designation by the FDA for Advanced Breast Cancer (Businesswire) - "ETX-636 will be administered alone or in combination with fulvestrant, a selective estrogen receptor degrader approved for the treatment of advanced hormone receptor HR+/HER2- breast cancer NCT06993844."

Fast track • Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Ensem Therapeutics Announces First Patient Dosed in Phase 1/2 Clinical Trial of ETX-636, a Potential Best-In-Class Allosteric Pan-Mutant-Selective PI3Kα Inhibitor and Degrader (Businesswire) - "Ensem Therapeutics...announced the first patient has been dosed in its phase 1/2 study of ETX-636, a potential best-in-class novel allosteric pan-mutant-selective PI3Kα inhibitor and degrader....This first-in-human, Phase 1/2 study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of ETX-636 in participants with advanced solid tumors harboring a PI3Kα mutation (NCT06993844). The first patient was dosed at START San Antonio (Amita Patnaik, M.D.), under an IND cleared by the FDA in April 2025. ETX-636 will be administered alone and in combination with fulvestrant, a selective estrogen receptor degrader approved for the treatment of advanced hormone receptor HR+/HER2- breast cancer."

Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

ETX-636, a novel allosteric pan-mutant-selective PI3Kα dual inhibitor and degrader with best-in-class potential (AACR 2025) - "Orthosteric ATP-competitive inhibitors, alpelisib and inavolisib, which inhibit both Wild-type (WT) and mutant PI3Kα, are approved in combination regimens for treating PIK3CA-mutant, HR+/HER2-, advanced or metastatic BrCA...In addition to greater biochemical selectivity for mutant PI3Kα over WT PI3Kα, ETX-636 has stronger target binding affinity, better on-target potency in biochemical and cellular pharmacodynamic assays, and demonstrates superior anti-tumor activity in vivo when compared to other allosteric, pan-mutant-selective PI3Kα inhibitors (i.e. RLY-2608 and STX-478)...In an ER-positive, HER2-negative, PI3Kα-mutant BrCA xenograft, ETX-636 is efficacious as a single agent and shows synergistic activity with fulvestrant, inducing tumor regression while being well-tolerated...In addition, based on pharmacokinetic, pharmacodynamic, efficacy, and toxicology studies, predicted human efficacious doses of ETX-636 are not projected to cause hyperglycemia. The preclinical..."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA • ER • HER-2 • PIK3CA

Phase 1/2 Study of ETX-636 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=233 | Recruiting | Sponsor: Ensem Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Phase 1/2 Study of ETX-636 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=233 | Not yet recruiting | Sponsor: Ensem Therapeutics

Monotherapy • New P1/2 trial • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Ensem Therapeutics Announces U.S. FDA IND Clearance to Initiate Clinical Development of ETX-636 (Businesswire) - "Ensem Therapeutics, Inc...today announced the clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) for ETX-636, a potential best-in-class novel allosteric pan-mutant-selective PI3Kα inhibitor and degrader, with its first-in-human study anticipated in the second quarter of 2025....In addition, ENSEM will present preclinical data on April 28th at the American Association for Cancer Research ('AACR') Annual Meeting in Chicago, Illinois, supporting a differentiated profile of ETX-636 and its potential to deliver clinical benefit to patients with tumors harboring activating PI3Kα mutations....The initial first-in-human, Phase 1/2 study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of ETX-636 in participants with advanced solid tumors harboring a PI3Kα mutation."

IND • New P1/2 trial • Preclinical • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Ensem Therapeutics To Present Preclinical Data for Potential Best-in-Class Allosteric Pan-Mutant-Selective PI3Kα Inhibitor and Degrader at San Antonio Breast Cancer Symposium (Businesswire) - "'Investigational new drug ('IND') submission on track for Q1 2025; Phase 1 trial will enroll patients with PI3Kα-mutated tumors, including breast cancer.'...ETX-636 is a novel orally bioavailable allosteric pan-mutant-selective PI3Kα inhibitor and degrader....Additionally, in an ER-positive, HER2-negative, PI3Kα-mutant breast cancer xenograft, ETX-636 is efficacious as a single agent and shows synergistic activity with the standard-of-care agent fulvestrant. ENSEM believes this molecule will significantly improve outcomes for patients with PI3Kα mutations, whether in cancer or rare diseases."

IND • New P1 trial • Preclinical • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer