PLX-66140 / Plexium - LARVOL DELTA

Preclinical characterization of PLX-66140, a potent and selective CDK2 degrader, for the treatment of CCNE1 amplified solid tumors and CDK4/6i resistant HR+/HER2- breast cancers (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CCNE1 • CDK2 • CDK4 • HER-2

Discovery of PLX-66140, a first-in-class, potent and selective CDK2 molecular glue degrader for CCNE1-amplified tumors (AACR 2026) - "Our development candidate, PLX-66140 provides compelling preclinical evidence and scientific rationale for clinical development in CDK4/6 inhibitor-naïve and -resistant HR+/HER2- breast cancer along with CCNE1 amplified solid tumors."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Uterine Cancer • CCNE1 • CDK2 • CRBN • ER • HER-2

Discovery of potent and selective bivalent CDK2 degraders that demonstrate activity in CCNE1amp driven tumors (AACR 2024) - "These data provide validation for CDK2 degradation as a therapeutic approach. Potent and selective CDK2 bivalent degraders were exploited as tools for studying the sensitivity of CCNE1 amplified tumor models to CDK2 degradation and dependence on E3 ligase. This proof-of concept study supports Plexium's current approach of discovering novel CDK2 molecular glue degraders for the treatment of CDK4/6 inhibitor-naïve and -resistant HR+/HER2- breast cancer, and CCNE1 amplified ovarian and endometrial cancers."

Breast Cancer • Endometrial Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • CCNA2 • CCNE1 • CDK2 • CRBN • HER-2

Discovery and characterization of novel, potent and selective CDK2 molecular glue degrader against CCNE1-amplified tumors (AACR 2025) - "Our potent and selective CDK2 molecular glue degraders provide preclinical evidence and scientific rationale for the treatment of CDK4/6 inhibitor-naïve and -resistant HR+/HER2- breast cancer, and CCNE1 amplified ovarian, gastroesophageal, and uterine cancers."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Uterine Cancer • CCNE1 • CDK2 • CRBN • HER-2

Discovery of potent and selective CDK2 molecule glue degraders for the treatment of HR+/HER2- breast cancer, and CCNE1 amplified tumors (AACR-NCI-EORTC 2025) - "We have discovered novel molecular glues that selectively degrade CDK2 resulting in preferential anti-proliferative activity in CCNE1 amplified cells with superior activity relative to ATP-competitive small molecule CDK2 inhibitors. CDK2 degraders result in potent degradation and anti-tumor activity in vivo. This supports the potential for CDK2 molecular glue degraders to treat CDK4/6 inhibitor-naïve and -resistant HR+/HER2- breast cancer, and CCNE1 amplified patient populations."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • CCNE1 • CDK2 • CRBN • HER-2

Plexium Announces Multiple Presentations at AACR 2025 with Selective Monovalent Degrader Programs Targeting SMARCA2…and CDK2 (PRNewswire) - "Plexium...announced today multiple presentations with the Company's selective monovalent degrader programs for SMARCA2...and CDK2 at the 2025 American Association for Cancer Research (AACR) Annual Meeting....PLX-61639, a selective, oral SMARCA2 degrader, demonstrated sustained PD response and single-agent efficacy in SMARCA4 mutant tumors; program is advancing through IND-enabling studies....Preclinical data was presented on its CDK2 selective molecular glue degrader, which exhibited superior selectivity over inhibitor-based approaches; program is targeting CCNE1 amplified cancers."

Preclinical • Oncology

Plexium Announces Two Oral Presentations and Multiple Posters at the American Association for Cancer Research (AACR) Annual Meeting 2025 (PRNewswire) - "Plexium...announced that initial Phase 1 clinical results with PLX-4545, a selective IKZF2 molecular glue degrader, and preclinical results from the Company's SMARCA2 monovalent direct degrader and CDK2 molecular glue degrader programs will be presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting..."

P1 data • Preclinical • Oncology