Kymera Therapeutics Advances Potential First-in-Class IRAK4 Degrader KT-474 into Pivotal Clinical Development with Sanofi Support

Jul 10, 2024 07:17 CST Updated 07:18

Sanofi

Pharmaceutical R&D Developer

▎WuXiEdited by Kant Content Team

Kymera Therapeutics recently announced that following a review by an independent data monitoring committee of the preliminary safety and efficacy data for the investigational protein degrader KT-474,Sanofi has notified Kymera of its plan to expand the ongoing Phase 2 clinical trials for Hidradenitis Suppurativa (HS) and Atopic Dermatitis (AD) to accelerate the advancement of this innovative therapy into the pivotal clinical study phase.

KT-474 (SAR444656) is a potential "first-in-class" IRAK4 degrader., is being developed for the treatment of immune-inflammatory diseases with significant patient needs such as HS and AD, as well as other potential conditions. IRAK4 is a key component of the myddosome protein complex and participates in the regulation of immune response signaling processes through interleukin-1 (IL-1) and toll-like receptors (TLR). IL-1 and toll-like receptors play critical roles in initiating immune responses against invading pathogens. IRAK4 is a scaffold kinase that resides at the intersection of innate and adaptive immune responses, exerting multiple functions through its kinase activity and scaffold capabilities.

KT-474 binds to IRAK4, recruiting E3 ubiquitin ligase to tag IRAK4 with ubiquitin. These "tags" direct the IRAK4 protein to be degraded by the cell's proteasome.Complete elimination of IRAK4 through targeted protein degradation can impact both its kinase and scaffolding functions, potentially enabling broad and well-tolerated anti-inflammatory effects, offering new therapeutic avenues for a range of immune-inflammatory diseases.

Previously published Phase 1 clinical trial results showed that KT-474 demonstrated promising activity in the treatment of atopic dermatitis.After 28 days of treatment, the itching severity in moderate to severe patients decreased by 63%, and the EASI score, which evaluates the extent and severity of the patient's condition, dropped by 36%.

Sanofi reached an agreement with Kymera in 2020 that could amount to up to 2 billion US dollarsR&D Collaboration, to jointly develop a potential "first-in-class" protein degradation therapy targeting IRAK4 for the treatment of immune-inflammatory diseases.

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References:

[1] Kymera Announces Expansion of KT-474 (SAR444656) HS and AD Phase 2 Studies Following Interim Review of Safety and Efficacy. Retrieved July 9, 2024, from https://investors.kymeratx.com/news-releases/news-release-details/kymera-announces-expansion-kt-474-sar444656-hs-and-ad-phase-2

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