Kymera Therapeutics Begins Phase 1 Trial of Oral STAT6 Degrader KT-621 for TH2 Immuno-Inflammatory Diseases

Kymera Therapeutics, a clinical-stage biopharmaceutical company based in Watertown, Massachusetts, has commenced a Phase 1 clinical trial in the United States for KT-621. This trial marks a significant milestone as KT-621 is the first oral degrader targeting STAT6 to enter clinical development. KT-621 aims to address various immuno-inflammatory diseases by harnessing the company’s targeted protein degradation (TPD) technology.

KT-621 has shown promising preclinical results, demonstrating activity similar to dupilumab, an injectable antibody used to treat several allergic and atopic diseases. Importantly, KT-621 was well-tolerated in a range of preclinical models of TH2 diseases, suggesting it could be a viable alternative to existing therapies. The initial data from this Phase 1 trial involving healthy volunteers is expected to be released in the first half of 2025.

Nello Mainolfi, PhD, Founder, President, and CEO of Kymera Therapeutics, highlighted the significance of KT-621 as the first oral STAT6-targeted medicine to advance into clinical trials. He emphasized that KT-621 illustrates Kymera’s capability to develop novel drugs that target previously undrugged proteins involved in disease processes. Mainolfi expressed optimism that KT-621, as a once-daily oral pill, could offer similar efficacy to biologics for patients with widespread allergic and atopic conditions. The Phase 1 clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of KT-621, employing a double-blind, placebo-controlled methodology with both single ascending dose and multiple ascending dose cohorts.

STAT6 is a crucial transcription factor in the IL-4/IL-13 signaling pathways and plays a central role in T helper type 2 (TH2) inflammation associated with allergic diseases. Historically, STAT6 has been challenging to target with small molecule inhibitors due to its protein-protein and protein-DNA interactions. However, KT-621 leverages targeted protein degradation, where a binding event triggers the degradation process, making it a promising candidate for treating conditions like atopic dermatitis, asthma, and chronic obstructive pulmonary disease.

Kymera Therapeutics is pioneering the field of targeted protein degradation to develop groundbreaking medicines that tackle critical health issues. By focusing on disease targets and pathways inaccessible with traditional therapies, Kymera aims to offer a new generation of effective and convenient treatments. The company has already brought the first degrader for immunological diseases into clinical trials and is advancing its oncology programs targeting proteins that are either undrugged or poorly drugged.

Founded in 2016, Kymera Therapeutics has gained recognition as one of Boston’s top workplaces. The company continues to push the boundaries of medical science by exploring new therapeutic avenues and developing innovative treatments that have the potential to significantly improve patients’ lives. The initiation of the KT-621 Phase 1 trial represents a crucial step forward in Kymera’s mission to leverage targeted protein degradation for therapeutic benefit, with the potential to transform the treatment landscape for several debilitating diseases.