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, MA, USA I May 19, 2023 I 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 initial dose escalation clinical data, focused on PK/PD and safety, later this year.”

Patients in the KT-253 Phase 1 open-label, dose escalation study will receive doses of KT-253 administered once every 3 weeks. The study is intended to identify the recommended Phase 2 dose for KT-253, and will be comprised of two arms, with ascending doses of KT-253 in each arm. The first arm will consist of patients with relapsed or refractory lymphomas and advanced solid tumors and the second arm will consist of patients with relapsed or refractory high grade myeloid malignancies and ALL.

More information on the Phase 1 study can be found at www.clinicaltrials.gov, identifier NCT05775406.

About Kymera Therapeutics
Kymera is a biopharmaceutical company pioneering the field of targeted protein degradation, a transformative approach to address disease targets and pathways inaccessible with conventional therapeutics. Kymera’s Pegasus platform is a powerful drug discovery engine, advancing novel small molecule programs designed to harness the body’s innate protein recycling machinery to degrade dysregulated, disease-causing proteins. With a focus on undrugged nodes in validated pathways, Kymera is advancing a pipeline of novel therapeutic candidates designed to address the most promising targets and provide patients with more effective treatments. Kymera’s initial programs target IRAK4, IRAKIMiD, and STAT3 within the IL-1R/TLR or JAK/STAT pathways, and the MDM2 oncoprotein, providing the opportunity to treat patients with a broad range of immune-inflammatory diseases, hematologic malignancies, and solid tumors.

Founded in 2016, Kymera is headquartered in Watertown, Mass. Kymera has been named a “Fierce 15” company by Fierce Biotech and has been recognized by both the Boston Globe and the Boston Business Journal as one of Boston’s top workplaces. For more information about our people, science, and pipeline, please visit www.kymeratx.com or follow us on Twitter or LinkedIn.

SOURCE: Kymera Therapeutics