Resmetirom is an oral, liver-targeting, once-daily THRβ-selective agonist, which in December 2022 became the first drug to meet its primary endpoints in Ph. III for NASH, demonstrating both NASH resolution and no worsening of fibrosis by biopsy over placebo in 316 test patients. Madrigal will file an NDA for resmetirom in 2023, allowing it to [...]

Bexotegrast is a dual-selective αvβ6-αvβ1 integrin inhibitor with surprising efficacy and safety data from a Ph. II trial in idiopathic pulmonary fibrosis (IPF). The αv integrins have been studied for decades in indications such as cancer and IPF. Both small molecule and antibody-based integrin inhibitors have demonstrated preclinical toxicities in non-human primates. This article highlights the unmet need for effective therapies for IPF and related conditions, a comparison of bexotegrast with other integrin binders, and possible reasons why bexotegrast is different in terms of safety.

bradanicline (ATA-101 or TC-5619) is a molecule first disclosed a decade ago by Targacept. It is a selective agonist of the alpha-7 neuronal nicotinic acetylcholine receptor, and was intended as a drug candidate for treatment of cognitive impairment in neurological disorders. It is highly selective for the CNS over peripheral receptor [...]

Ziretaxestat, an oral autotaxin (ATX) inhibitor originated by Galapagos, once garnered excitement as the first molecule to complete a Ph. III clinical program in idiopathic pulmonary fibrosis since the approvals of nintedanib and pirfenidone. Following the disappointing clinical data and discontinuation of the molecule, this annotation revisits ziritaxestat in the context of other inhibitors, recaps the therapeutic hypothesis and how it was discovered, summarizes notable molecular properties for drug discovery scientists, and discusses what happened and what’s next.

The Mirum Pharmaceuticals IBAT bile acid transporter inhibitor, maralixibat , has a long history, having been first patented by scientists at Searle in 1994 and published by the time Searle became part of Pharmacia in 2005 . It was finally approved in Sep. 2021 for treatment of cholestatic pruritis in patients with Alagille Syndrome, and is [...]