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.

The Eternity Bioscience/Shanghai Hengrui RORγ antagonist, SHR168442, is a skin-restricted, topical compound intended to treat psoriasis. As a master regulator of Th17 immune cells which are significantly involved in allergic diseases, both positive and negative oral modulators of RORγt had been hotly pursued, though many have ceased clinical [...]

The AstraZeneca oral RORgt inverse agonist, AZD0284 , is an inverse agonist of the nuclear receptor RORC2 (RORγt). Reviewer Chris Gampe says, “targeting the activation and function of Th17 cells has been successful for the treatment of autoimmune disease (cf. IL-17, IL-17R, IL-23 Abs). RORC2 is the transcription factor that controls Th17 [...]

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 [...]