The ImmunoMet OXPHOS modulator (PC1 inhibitor), IM156 , is a derivative of the long-used biguanide diabetes drug, metformin, that appears to have activity in lung fibrosis models. The therapeutic hypothesis for IPF is that myofibroblasts play an essential role in extracellular matrix remodeling and fibrogenesis that lead to loss of pulmonary [...]

Context. CHF-6366 (Chiesi Farmaceutici S.p.A) is a muscarinic antagonist and β2 agonist (MABA) being developed as an inhaled treatment for respiratory diseases. Muscarinic antagonists and β2 agonists both act to inhibit bronchoconstriction, but through different mechanisms, making the combination of both agents a desirable strategy for [...]

BAY 2925976 is a novel oral ARα2C antagonist developed by Bayer for the treatment of OSA (obstructive sleep apnea), a widespread condition affecting nearly one billion people globally. Despite the availability of mechanical treatments like CPAP, poor adherence rates highlight the need for more effective interventions. BAY 2925976 demonstrated a preclinical proof of concept for ARα₂C modulation as a potential therapeutic approach for OSA. In this article, we detail the discovery of BAY 2925976, as highlighted by Michael Hahn at the ACS Fall 2024 First-Time Disclosures session in Denver, CO.

The Shionogi P2X3 ligand-gated ion channel antagonist, sivopixant ( S-600918 ), is an oral Ph. II candidate for refractory chronic cough, which recently completed a its Ph. IIb study, overcoming the projected high dose requirement of a prior preclinical candidate. The molecule has a very polar core structure with both a dioxotriazine and [...]

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.