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Kymera Therapeutics Doses First Patient in Phase 1 Oncology Trial of MDM2 Degrader KT-253
KT-253 is a novel, highly potent and selective heterobifunctional degrader of the MDM2 oncoprotein with a differentiated profile from small molecule
About this update from Kymera Therapeutics, Inc.
[{"type":"text","content":"KT-253 is a novel, highly potent and selective heterobifunctional degrader of the MDM2 oncoprotein with a differentiated profile from small molecule inhibitors in development for the treatment of liquid and solid tumors Company plans to share initial safety and proof-of-mechanism clinical data in second half of 2023 WATERTOWN, Mass., May 19, 2023 (GLOBE NEWSWIRE) -- Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing targeted protein degradation (TPD) to deliver novel small molecule protein degrader medicines, has recently dosed the first patient in the Phase 1 multicenter, open-label, dose-escalation clinical trial evaluating its investigational MDM2 degrader KT-253. The Phase 1 study will evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and clinical activity of ascending doses of KT-253 in adult patients with relapsed or refractory high grade myeloid malignancies, acute lymphocytic leukemia (ALL), lymphomas, and solid tumors. KT-253 targets MDM2, the crucial regulator of the most common tumor suppressor, p53. p53 remains intact (wild type) in close to 50% of cancers, meaning that it retains its ability to modulate cancer cell growth. While small molecule inhibitors have been developed to stabilize and upregulate p53 expression, they have been found to induce a feedback loop that increases MDM2 protein levels, which can repress p53 and limit their efficacy. In preclinical studies, KT-253 has shown the ability to overcome the MDM2 feedback loop and rapidly induce cancer cell death, even with brief exposures. This may also improve KT-253’s therapeutic index, potentially providing the opportunity for an improved efficacy and safety profile. “At Kymera, we are focused on applying targeted protein degradation to well-validated targets that cannot be addressed, or are inadequately addressed, with conventional medicines. We believe that KT-253 has the potential to overcome the inherent limitations of small molecule MDM2 inhibitors and provide a more effective option for patients with a variety of cancers,” said Jared Gollob, M.D., Chief Medical Officer of Kymera Therapeutics. “The initiation of dosing in this study represents important progress toward understanding the pharmacology and safety of this first-in-class investigational medicine, and we look forward to sharing ...