Sanofi's 'Star Small Molecule' IRAK4 Degrader SAR444656 Granted IND Approval in China for Atopic Dermatitis and Hidradenitis Suppurativa

Jan 21, 2025 09:18 CST Updated 09:18

Sanofi

Pharmaceutical R&D Developer

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On January 20, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced that Sanofi's Class 1 new drug SAR444656 had received tacit approval for clinical trials.The indications under development include atopic dermatitis (AD) and hidradenitis suppurativa (HS).。

Public information shows that KT-474 (SAR444656) isAn IRAK4 protein degrader，By Kymera Therapeutics and SanofiCo-development. The productOnce wasDrugHunter Website (drughunter.com)Included in the 2023 AnnualTop Ten "Star" Small Molecules. In addition,Sanofi once2023R&D Day IntroductionA list of new drugs with blockbuster potential in its pipeline, including SAR444656.

Screenshot source:CDE Official Website

IRAK4 is a scaffold kinase at the intersection of innate and adaptive immune responses, performing multiple roles through its kinase activity and scaffold function.ItInvolved in the signal transduction process of regulating immune responses through interleukin-1 (IL-1) and toll-like receptors (TLR).The abnormalities in these signaling pathways are the underlying mechanisms of various inflammatory diseases, including rheumatoid arthritis, atopic dermatitis, hidradenitis suppurativa, and more.

▲Introduction to SAR444656 (Image Source:Sanofi Official Website)

According to publicly available information from Sanofi, SAR444656 canBy binding with IRAK4, it recruits E3 ubiquitin ligase to tag IRAK4 with ubiquitin. These "tags" direct the IRAK4 protein to be degraded by the cell's proteasome., thereby blocking IRAK4-mediated signaling. In addition,Complete elimination of IRAK4 through targeted protein degradation can impact both its kinase and scaffolding functions, potentially leading to broad and well-tolerated anti-inflammatory effects, offering new therapeutic avenues for a range of immune-inflammatory diseases.

At the end of 2022, Kymera announced positive Phase 1 clinical results for KT-474 in patients with atopic dermatitis (AD) and hidradenitis suppurativa (HS).Test ResultsPharmacokinetic/Pharmacodynamic (PK/PD) results showed,KT-474 demonstrates potent degradation effects in both blood and active skin lesions, achieving up to over 90% degradation.IRAK4。The activity test results of anti-inflammatory biomarkers showed that KT-474 can broadly inhibit pro-inflammatory cytokines and chemokines with good safety.In ex vivo cytokine stimulation assays, KT-474 demonstrated broad and deep inhibition of multiple disease-related cytokines, with an 84% inhibition rate in HS patients and up to a 98% inhibition rate in AD patients.。

According toClinicalTrialsAccording to the official website, Sanofi is currently conducting two international multicenter Phase 2 clinical trials to evaluate SAR444656 for the treatment ofAdult patients with moderate to severe hidradenitis suppurativa, adult patients with moderate to severe atopic dermatitisEfficacy and safety.This timeSAR444656 Approved for Clinical Trials in China, Signaling the Product’s Entry into the Clinical Research Phase in the Country.

References:

[1] Official website of the Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Jan 20, 2025, from https://www.cde.org.cn/main/xxgk/listpage/da6efd086c099b7fc949121166f0130c

[2]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

[3] Sanofi official website. From https://www.sanofi.com/en/our-science/our-pipeline

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