Merck's First-in-Class Oral TLR7/8 Inhibitor Enpatoran Approved for Clinical Trial in China for Systemic Lupus Erythematosus

By Yang Guang

On March 7, the CDE website showed that Merck's enpatoran (M5049) clinical trial application was approved by the NMPA for the treatment of systemic lupus erythematosus (SLE). It is reported that enpatoran is a potential "first-in-class" oral Toll-like receptor (TLR) 7/8 inhibitor.

Toll-like receptors (TLRs) are a group of pattern recognition receptors in the innate immune system that can recognize conserved microbial structures such as lipopolysaccharides, flagellin, and viral RNA. TLR7 and TLR8 can recognize microbial single-stranded RNA, purine analogs, and imidazoquinolines, inducing the production of inflammatory cytokines and triggering immune responses to protect the host. However, abnormal activation of TLR7/8 has potential pathogenicity and is associated with the progression of certain autoimmune diseases such as lupus.

Enpatoran, an oral TLR7/8 inhibitor developed by Merck KGaA, is currently under development for the treatment of lupus erythematosus (systemic lupus erythematosus and cutaneous lupus erythematosus) and COVID-19.