RPT193, an oral, second-generation CCR4 inhibitor from RAPT Therapeutics, is in Ph. II clinical trials (400 mg QD) to treat atopic dermatitis (AD) (NCT05399368) and asthma (NCT05935332). CCR4 has been a long outstanding therapeutic target for treating inflammatory diseases, but despite many efforts, no molecule inhibiting this receptor has progressed beyond Ph. I for these indications.

BMS-986251 is an inverse agonist of RORgt, a hot target in inflammation for a significant period. Unfortunately it looks like development hit a wall in this space, and several publications of various company’s RORgt modulators have appeared in the last several months. Chemically, 251 is interesting with 5 stereocenters, none of which look [...]

JTE-052 (delgocitinib) is a pan-JAK kinase inhibitor approved as a topical ointment for treatment of atopic dermatitis in Japan. The compound has an interesting azetidine-containing diazaspirocycle core and a relatively high sp3-fraction for a kinase inhibitor.

The Biocryst oral plasma kallikrein inhibitor, berotralstat (BCX7353) , was recently approved as the first non-steroidal treatment for prevention of hereditary angioedema attacks. The molecule is given orally (150 mg QD) despite having two basic amines. Interestingly for a chronically administered drug, the molecule is noted to have QT [...]

LEO 39652 (LEO Pharma “dual-soft” topical PDE4 inhibitor soft drug clinical candidate)