Sanofi has informed Kymera Therapeutics that it will advance KT-485/SAR447971, a first-in-class oral IRAK4 degrader, into clinical studies while discontinuing development of KT-474. The decision reflects KT-485's compelling preclinical profile and marks a significant milestone in the companies' collaboration to develop targeted protein degradation therapies for immunological diseases.
Superior Preclinical Performance Drives Selection
KT-485 demonstrated an improved target product profile compared to KT-474 in preclinical testing, showing greater potency and selectivity along with a generally improved overall profile. The next-generation IRAK4 degrader is expected to advance into Phase 1 testing next year following extensive preclinical work supporting its robust development potential.
"In preclinical testing, KT-485 demonstrated an improved target product profile as compared to KT-474. With greater potency and selectivity and a generally improved overall profile, KT-485 is best-positioned to capitalize on the significant potential of IRAK4 degradation," commented Nello Mainolfi, PhD, Founder, President and CEO of Kymera Therapeutics.
Novel Mechanism Targets Multiple Immune Functions
KT-485 represents a first-in-class approach to treating immuno-inflammatory diseases through targeted degradation of IRAK4, a master regulator of innate immunity and key protein of the myddosome complex. IRAK4 mediates signaling through IL-1 and toll-like receptors, functioning as a scaffolding kinase at the interface of innate and adaptive immune responses.
Unlike conventional small molecule inhibitors, IRAK4 degradation eliminates the protein completely, impacting both kinase and scaffolding functions. This comprehensive approach has the potential to achieve broad, well-tolerated anti-inflammatory effects, providing a novel therapeutic strategy for various immune-inflammatory diseases.
Substantial Financial Milestones and Partnership Terms
Under the collaboration agreement, Kymera achieved a $20 million milestone in the second quarter of 2025 related to preclinical activities associated with KT-485. The company is eligible to receive up to $975 million in potential clinical, regulatory and commercial milestones, including an additional milestone upon the start of Phase 1 clinical testing.
Sanofi has exercised its participation election right for the IRAK4 target, and Kymera may opt-in to a 50/50 development and profit share of KT-485 in the United States. The collaboration also includes double-digit royalties for Kymera.
Strategic Focus on Transforming Immunology Treatment
The partnership between Sanofi and Kymera reflects both companies' commitment to targeting the IRAK4 pathway with degraders that are functionally differentiated from small molecule inhibitors. Sanofi is collaborating with Kymera on IRAK4 degrader development outside of oncology and immuno-oncology fields.
"Sanofi's intention to advance KT-485 into clinical testing and to direct all collaboration resources to the next-generation IRAK4 degrader is a reflection of the molecule's compelling preclinical profile and of Sanofi's and Kymera's commitment to transform immunology treatment paradigms," Mainolfi stated.
Clinical data generated to date demonstrates the potential of IRAK4 degradation to deliver the combined activity of upstream biologics in an oral drug format for multiple diseases, representing a significant advancement in convenience and accessibility for patients with immunological conditions.
