Kymera to Present New Phase 1 Data on MDM2 Degrader KT-253 at ASCO

Kymera Therapeutics, Inc., a biopharmaceutical company based in Watertown, Massachusetts, has announced promising new clinical data for KT-253, an innovative MDM2 degrader. This information comes from an ongoing Phase 1 dose escalation trial and will be showcased at the American Society of Clinical Oncology (ASCO) Annual Meeting from May 31 to June 4, 2024, in Chicago, Illinois.

The clinical data stems from 18 patients enrolled in the Phase 1 trial, divided into two arms: Arm A, consisting of patients with solid tumors and lymphomas, and Arm B, which includes patients with high-grade myeloid malignancies. As of January 26, 2024, Arm A included 13 patients across four dose levels, while Arm B comprised five patients at two dose levels. The most commonly treated solid tumors were Merkel cell carcinoma (MCC), adenoid cystic carcinoma (ACC), and uveal melanoma.

Key findings from Arm A indicate one partial response in an MCC patient and stable disease in patients with fibromyxoid sarcoma, ACC, and renal cell cancer. Arm B reported a complete response and a partial response in patients with post-myeloproliferative neoplasm acute myeloid leukemia (AML). Pharmacodynamic data showed that KT-253 induces rapid upregulation of plasma GDF-15 protein and activation of CDKN1A and PHLDA3 mRNA levels in the blood. Furthermore, the drug demonstrated a dose-dependent increase in plasma concentration, aligning with projected efficacious doses.

Adverse events (AEs) associated with KT-253 were generally manageable, including nausea, fatigue, headache, and vomiting. There was one dose-limiting toxicity in Arm A, manifesting as Grade 2 nausea and fatigue, which led to discontinuation. Importantly, no instances of neutropenia or thrombocytopenia were observed. A serious adverse event of Grade 3 hypotension occurred in a patient with decreased oral intake in Arm A.

These preliminary findings will be expanded upon in a poster presentation at the ASCO meeting, which will include data from three additional patients in each arm, as well as updated pharmacokinetic, pharmacodynamic, and safety information. The poster will be accessible on Kymera’s website on June 1, 2024.

KT-253 is a groundbreaking MDM2 degrader that targets the MDM2 protein, a key regulator of the p53 tumor suppressor. P53 is preserved in about half of all cancers and plays a vital role in controlling cancer cell growth. While small molecule inhibitors have been developed to stabilize p53, they have not shown significant clinical benefits due to their inability to overcome a feedback loop that elevates MDM2 levels when p53 is upregulated. KT-253 is designed to bypass this loop, effectively inducing cancer cell death with short exposure times.

Kymera Therapeutics is advancing KT-253 through its Phase 1 trial to assess the drug's safety, tolerability, pharmacokinetics, and clinical activity in patients with relapsed or refractory high-grade myeloid malignancies, including AML, acute lymphocytic leukemia (ALL), lymphomas, and solid tumors. The company plans to complete this study and present additional clinical data later in 2024.

Kymera Therapeutics, a pioneer in targeted protein degradation (TPD), is committed to developing medicines that address significant health issues and improve patients' lives. The company focuses on creating oral small molecule degraders to offer new, effective treatments for diseases previously untreatable by conventional methods. Founded in 2016, Kymera has earned recognition as one of Boston’s top workplaces and continues to make strides in both immunological and oncological treatments.