Inaxaplin (VX-147), developed by Vertex, is an inhibitor of APOL1 channel activity currently in a Ph. II/III pivotal study for the treatment of chronic kidney disease caused by specific variants of the APOL1 gene. It was recently granted Breakthrough Therapy designation by the FDA and PRIME designation by the EMA. The discovery story, which is an excellent case study for the use of MetID. Inaxaplin has been called “the most important genomic-driven drug discovery for chronic kidney disease this century”, acting on a target with a fascinating human genetic validation story.

The Takeda cholesterol 24-hydroxylase inhibitor, soticlestat (TAK-935, previously OV935) is a potent, highly selective, first-in-class inhibitor of the brain-specific enzyme cholesterol 24-hydroxylase (CH24H). Cholesterol 24-hydroxylase converts cholesterol to 24S-hydroxycholesterol, which acts as a positive allosteric modulator of [...]

Toward an oral, once-daily non-peptide STT2 agonist. Paltusotine a novel oral somatostatin receptor 2 (SST2) agonist and Crinetics’ lead investigational drug, is intended to treat acromegaly and neuroendocrine tumors (NETs) in carcinoid syndrome. Both diseases have been treated with surgery and injectable somatostatin [...]

Zilucoplan is a macrocyclic peptide-containing drug with 15 amino acids in total, targeting the challenging-to-drug C5 complement protein and formulated for self-administered once-daily SC injection. In Sept. 2023, zilucoplan received its first global approval in Japan, followed in Oct. 2023 by FDA approval for gMG patients who are AChR antibody-positive, making zilucoplan the first drug derived from mRNA display for cyclic peptides to be approved. This case study discusses how zilucoplan was discovered and why it’s an important scientific milestone for the industry.

The Pfizer CFTR potentiator, CP-628006 , enhances CFTR function in cystic fibrosis patient-derived airwell cells with a distinct mechanism of action from existing potentiators such as ivacaftor. It has a unique chemical structure, and in contrast to other potentiators does not seem to inhibit the channel at high concentrations of drug and [...]