SIM0711 / Simcere - LARVOL DELTA

Discovery and Characterization of SIM0711: a Potent and Selective IRAK4 PROTAC with Improved Efficacy and Safety (ACR Convergence 2025) - "SIM0711 was benchmarked against KT-474 (an IRAK4 PROTAC) and PF-06650833 (a selective kinase inhibitor). These findings support SIM0711 as a potential best-in-class IRAK4 PROTAC for the treatment of a range of autoimmune diseases. Its robust IRAK4 degradation, superior anti-inflammatory efficacy, and favorable pharmacological profile highlight its strong therapeutic potential. IND submission is expected by Q3 2025."

Clinical • Immunology • Inflammation • Targeted Protein Degradation • CXCL8 • IL1R1 • IL6 • IRAK4 • TLR4 • TLR7 • TLR8 • TLR9

Discovery and characterization of SIM0711, a potent and selective IRAK4 PROTAC with Enhanced Efficacy and Safety (EADV 2025) - "Its activity was compared with either the benchmark IRAK4 PROTAC (KT-474) or the benchmark IRAK4 inhibitor (PF-06650833). These findings establish SIM0711 as a best-in-class IRAK4 PROTAC with the potential to treat a wide range of autoimmune and inflammatory diseases. Its robust IRAK4 degradation, superior anti-inflammatory efficacy, and favorable drug properties support its further development, with an IND submission anticipated in H2 2025."

Clinical • Dermatitis • Immunology • Inflammation • Targeted Protein Degradation • CXCL8 • IL1R1 • IL33 • IL5 • IL6 • IRAK4

DISCOVERY AND CHARACTERIZATION OF SIM0711, A POTENT AND SELECTIVE IRAK4 PROTAC WITH ENHANCED EFFICACY AND SAFETY (EULAR 2025) - "Its activity was compared with either the benchmark IRAK4 PROTAC (KT-474) or the benchmark IRAK4 inhibitor (PF-06650833). These findings establish SIM0711 as a best-in-class IRAK4 PROTAC with the potential to treat a wide range of autoimmune and inflammatory diseases. Its robust IRAK4 degradation, superior anti-inflammatory efficacy, and favorable drug properties support its further development, with an IND submission anticipated in H2 2025."

Clinical • Dermatitis • Immunology • Inflammation • Targeted Protein Degradation • CXCL8 • IL1R1 • IL33 • IL5 • IL6 • IRAK4

Discovery and characterization of SIM0711 a potent and selective IRAK4 PROTAC with enhanced efficacy and safety (IMMUNOLOGY 2025) - "In comparison to benchmark PROTAC KT-474, SIM0711 induced near-complete IRAK4 degradation in diverse primary human immune cells and stromal cell lines, demonstrating faster degradation kinetics in THP-1 cells and primary human monocytes in vitro. Furthermore, SIM0711 demonstrated improved bioavailability, favorable PK/PD characteristics, and good safety profiles across multiple species. Taken together, these data support the further development of SIM0711 as a potential BIC IRAK4 PROTAC for treating a range of inflammatory and autoimmune diseases with expected IND submission in H2 2025.Keywords: Animals Rodent; Cells Monocytes/Macrophages; Diseases Autoimmunity; Molecules Protein Kinases/Phosphatases; Processes Inflammation"

Clinical • Dermatitis • Immunology • Inflammation • Targeted Protein Degradation • CXCL8 • IL1R1 • IL33 • IL5 • IL6 • IRAK4

Preclinical data of four innovative autoimmune drugs from Innovent will be published in 2025AAI [Google translation] (Simcere Press Release) - "SIM0711 is an oral protein degradation targeted chimeric (PROTAC) molecule independently developed by the scientific team of Innovent, which can potently and selectively degrade IRAK4. It has shown stronger inflammation inhibition than IRAK4 kinase inhibitors or other PROTACs with the same target in various cell studies. In an IL-33-induced skin inflammation mouse model, SIM0711 dose-dependently reduced skin inflammation and almost eliminated the secretion of IL-5 downstream of the inflammatory site. In addition, SIM0711 exhibited excellent pharmacokinetic/pharmacodynamic properties in experiments on multiple species, including high bioavailability and good safety. The project is expected to submit an IND application in the second half of 2025."

IND • Preclinical • Immunology • Inflammation