Immunology Investor Event

sanofi SAR444656 (KT-474): Potent orally bioavailable IRAK4 degrader TLRs Y MyD88 IRAK4 IRAK4 kinase inhibitor Inactive IRAK4 kinase PIRF5/7 NFKB IL1/IL18/IL33/IL36 scaffold function IRAK4 protein degrader (SAR444656) Inactive kinase Disabled scaffold function PIRF5/7 TNFα/ẞ, inflammatory cytokines (IL6, TNFα) & other inflammatory mediators 50 Immunology Investor Event Change from Baseline Mean (± SE) Percent IRAK4 -40 -60 Ph1 MAD PBMC IRAK4 (Kymera) -80 -100 1 2 3 4 7 14 17 21 Day Ph1 study ongoing → Placebo 25 mg QD ✰ 50 mg QD 100 mg QD 200 mg QD LLOQ 28 Degradation of IRAK4 protein abolishes its kinase activity and scaffold function Potential for oral immunology pathway drug across multiple indications SAR444656 treatment resulted in potent IRAK4 protein degradation in blood (PBMC) and skin of healthy volunteers

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