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 [...]

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.

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.

Voxelotor is a first-in-class, reversible covalent aldehyde drug that prevents the hemoglobin polymerization, a primary driver of sickle cell disease. Approved in 2019 , this molecule represented a scientific milestone as a modern example of a reversible covalent drug being approved in a chronic indication. It is the first oral drug that [...]

Context. Etavopivat (Forma Therapeutics) is an oral erythrocyte pyruvate kinase activator being developed for sickle cell disease and other hemoglobinopathies , previously reported in 2019 . Hydroxyurea had been the only approved drug for sickle cell disease until the “sickle cell drug boon” began in 2017 starting with approval of l-glutamine [...]