Ensem Therapeutics Highlights Novel, Potent, and Selective Oral pan-KRAS and WRN Inhibitors with Best-in-Class Potential

Preclinical Data to be Presented at the AACR Annual Meeting Showcasing Ensem’s Advancements in Next-Generation Precision Oncology

WALTHAM, Mass.--(BUSINESS WIRE)--Ensem Therapeutics, Inc. (ENSEM), a clinical-stage, oncology-focused biopharmaceutical company, today announced presentations of preclinical data at the American Association for Cancer Research (AACR) Annual Meeting, being held April 17–22 in San Diego, CA. The data support the differentiated preclinical profiles of ETX-929, a pan-KRAS inhibitor for the treatment of KRAS-altered solid tumors, and ETX-880, a covalent WRN inhibitor for the treatment of microsatellite instability-high (MSI-H) solid tumors.

“These AACR presentations underscore the breadth and depth of ENSEM’s oncology pipeline, fueled by our proprietary Kinetic Ensemble^® platform,” said Shengfang Jin, PhD, Co-Founder, President, and Chief Executive Officer of ENSEM. “With ETX-929 and ETX-880, we are advancing potential best-in-class small molecule inhibitors against two of the most compelling targets in oncology today—KRAS and WRN. These programs, alongside our clinical-stage PI3Kα program ETX-636, demonstrate the power of our platform to systematically tackle high-value, difficult-to-drug targets with differentiated molecules.”

AACR Presentation Details

Details of the presentations are as follows:

ETX-929 (Pan-KRAS Inhibitor)

• Title: ETX-929, a potential best-In-class, oral, highly potent and selective dual ON / OFF state Pan-KRAS small molecule inhibitor for the treatment of KRAS mutant and wild-type amplified cancers
• Poster ID: 418
• Session: Novel Antitumor Agents 1
• Date/Time: 4/19/2026 2PM – 5PM PT
• Location: Poster Section 17, Poster Board Number: 21

ETX-880 (Covalent WRN Inhibitor)

• Title: ETX-880, a potential best-in-class, oral, highly potent and selective covalent inhibitor of Werner helicase for the treatment of microsatellite instability-high (MSI-H) cancers
• Poster ID: 423
• Session: Novel Antitumor Agents 1
• Date/Time: 4/19/2026 2PM – 5PM PT
• Location: Poster Section 17, Poster Board Number: 26

About ETX-929

ETX-929 is a potent and selective oral pan-KRAS inhibitor designed leveraging ENSEM’s proprietary Kinetic Ensemble^® platform. ETX-929 inhibits multiple KRAS-mutant variants, including KRASG12D, KRASG12V, KRASG12C, and other clinically relevant mutations, in both the active (GTP-bound/ON) and inactive (GDP-bound/OFF) states. KRAS is the most frequently mutated oncogene in human cancers, driving approximately 25% of all solid tumors, including pancreatic, colorectal, and non-small cell lung cancers. Despite recent advances in allele-specific KRAS inhibitors, there remains a significant unmet need for pan-KRAS therapeutics that can address the full spectrum of KRAS-driven cancers. ETX-929 has demonstrated potent anti-tumor activity in preclinical models and has completed IND-enabling studies with anticipated IND clearance in Q2 2026.

About ETX-880

ETX-880 is a covalent, potent, oral inhibitor of Werner syndrome ATP-dependent helicase (WRN) designed leveraging ENSEM’s Kinetic Ensemble^® platform. WRN helicase has emerged as a compelling synthetic lethal target in microsatellite instability-high (MSI-H) cancers. MSI-H tumors arise from defects in the DNA mismatch repair pathway and are found across multiple tumor types, including colorectal, endometrial, gastric, and ovarian cancers. While immune checkpoint inhibitors have demonstrated clinical benefit in MSI-H cancers, 40–70% of patients either do not respond or eventually develop resistance, underscoring the need for novel therapeutic approaches. ETX-880’s covalent binding mechanism is designed to deliver deep and sustained WRN inhibition, and the compound has demonstrated selective anti-proliferative activity against MSI-H cancers in preclinical studies. ETX-880 is currently at the IND-enabling stage.

About Ensem Therapeutics

ENSEM is a pioneering drug discovery and development company advancing innovative small-molecule precision medicines for oncology. Leveraging its proprietary Kinetic Ensemble^® platform, ENSEM integrates AI-driven deep learning, advanced computational modeling, and cutting-edge experimental approaches to identify non-obvious binding pockets and accelerate structure-based drug design, with a focus on high-value and historically difficult-to-drug targets.

ENSEM’s lead clinical program, ETX-636, is a potential first-in-class and best-in-class allosteric pan-mutant-selective PI3Kα dual inhibitor and degrader currently in a global Phase 1/2 clinical trial (NCT06993844) for patients with PIK3CA-mutant, HR+/HER2- advanced breast cancer. ETX-636 has received Fast Track designation from the U.S. FDA. In addition to ETX-636, ENSEM is advancing a deep pipeline of preclinical programs, including ETX-929 (pan-KRAS) and ETX-880 (WRN), targeting high-value oncology indications.

For more information, visit www.ensemtx.com or follow ENSEM on LinkedIn.