In the Phase 1 trial, KT-474 showed evidence of robust IRAK4 degradation in blood and skin lesions as well as a systemic anti-inflammatory effect in hidradenitis suppurativa (HS) and atopic dermatitis (AD) patients and was generally well-tolerated

Clinical endpoints addressing disease burden and symptoms demonstrated a highly competitive profile with substantial responses in the majority of both HS and AD patients with moderate-to-severe disease

Kymera’s partner Sanofi to initiate Phase 2 clinical trials of KT-474 in HS and AD, with first study in HS planned for initiation in 2023

WATERTOWN, MA, USA I May 18, 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, today presented positive Phase 1 clinical data from its lead program, KT-474 (SAR444656), a potent, highly selective, orally bioavailable IRAK4 degrader. The Company delivered an oral presentation at the European Academy of Dermatology and Venereology (EADV) Symposium, taking place from May 18-20, 2023, in Seville, Spain.

IRAK4 is a key protein involved in inflammation mediated by the activation of toll-like receptors (TLRs) and IL-1 receptors (IL-1Rs). Aberrant activation of these pathways is the underlying cause of multiple immune-inflammatory conditions. KT-474, a potential first-in-class IRAK4 degrader, is in development for the treatment of TLR/IL-1R-driven immune-inflammatory diseases with high unmet medical need, such as hidradenitis suppurativa (HS), atopic dermatitis (AD), and potentially others. KT-474 is designed to block TLR/IL-1R-mediated inflammation more broadly compared to monoclonal antibodies targeting single cytokines, and to enable pathway inhibition that is superior to IRAK4 kinase inhibitors by abolishing both the kinase and scaffolding functions of IRAK4, thereby providing a novel therapeutic approach.

The data demonstrated that KT-474 administered to HS and AD patients had safety, PK and PD similar to healthy volunteers, achieved robust IRAK4 degradation in blood and skin associated with a systemic anti-inflammatory effect, and showed promising clinical activity in HS and AD. The Company previously reported on the full data set in December, and today’s presentation marks the first time these results have been shared at a major scientific meeting.

“The KT-474 Phase 1 trial was a substantial accomplishment for Kymera, showcasing the high fidelity of PK/PD and safety translation from preclinical species to humans for our heterobifunctional degrader platform. KT-474 exhibited clinical activity in HS and AD patients that we believe is superior to IRAK4 small molecule kinase inhibitors and appears competitive with standard of care biologics and other agents in development in both HS and AD,” said Jared Gollob, M.D., Chief Medical Officer at Kymera Therapeutics. “These results validate IRAK4 degradation as a potential best-in-class mechanism in TLR/IL-1R-driven inflammatory diseases that has the potential to improve the lives of patients with conditions like HS and AD and potentially other indications. We look forward to sharing additional updates as our partner Sanofi initiates Phase 2 clinical trials of KT-474 in HS and AD, with the first study in HS planned for initiation in 2023.”

Presentation at EADV
Title: Safety and Efficacy of IRAK4 Degrader KT-474 (SAR444656) for Hidradenitis Suppurativa and Atopic Dermatitis
Presentation ID: FC02.05
Session Time: 11:45 – 12:00 PM CEST, May 18, 2023
Location: Auditorium 3
Presenter: Jared Gollob, M.D., Chief Medical Officer, Kymera Therapeutics

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 or follow us on Twitter or LinkedIn.

SOURCE: Kymera Therapeutics