Netherton syndrome is a rare disease caused by loss of activity of the lympho-epithelial Kazal-type-related inhibitor (LEKTI) protein, which in turn is caused by mutations in its encoding gene, SPINK5. This deficiency leads to the triggering of the kallikrein (KLK) signaling cascade resulting in skin barrier dysfunction, inflammation and atopy. At the recent Society for Investigative Dermatology meeting, Biocryst Pharmaceuticals Inc. presented early data on BCX-17725, a KLK5/KLK14 inhibitor fusion protein developed to restore LEKTI functioning in patients with Netherton syndrome.

Transforming acidic coiled-coil-containing protein 3 (TACC3) is a core member of multiprotein complexes that regulate microtubule- and centrosome-related processes. Its aberrant expression is found in several cancer types with poor prognosis, thus highlighting it as a candidate therapeutic target. Researchers from Beijing Konruns Pharmaceutical Co. Ltd. have presented data for KC-1101, a TACC3 inhibitor for treating aggressive cancers with centrosome amplification.

Type 2 diabetes is marked by insulin resistance coupled with insufficient insulin secretion due to early β-cell dysfunction and progressive loss of β-cell mass. Pdx1 and MafA, critical for maintaining β-cell function, are progressively reduced under metabolic stress and in patients, driving disease progression. Researchers at the University of Pittsburgh have reported efficacy data demonstrating successful pancreatic delivery of GPX-002, an AAV-Pdx1/MafA construct, in HFD mice.

Werner syndrome helicase (WRN), belonging to the RecQ helicase family, represents a synthetic lethal vulnerability in MSI-H cancers, providing a strong rationale for therapeutic inhibition. Researchers from Simcere Zaiming Pharmaceutical Co. Ltd. reported the discovery and preclinical characterization of ZMS-4084, a novel WRN inhibitor.

Increasing evidence supports metabotropic glutamate mGlu7 receptor as a promising target in psychiatric disorders. Neurosterix Pharma Sarl has presented data on NTX-819, a potential first-in-class, potent and selective negative allosteric modulator (NAM) of mGlu7. NTX-819 was tested in vivo in rats using behavioral tests that are relevant to disorders such as obsessive-compulsive disorder (OCD), agitation and mania/psychosis.

Directed evolution has become a central pillar in gene therapy. This engineering strategy enables the generation of more efficient variants of genetic editors and delivery vectors. Molecular diversification methods are increasingly sophisticated and are now accelerated by machine learning and AI tools, as showcased at the 29th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) held in Boston this week.

Work at Blueprint Medicines Corp. to identify a selective and potent CDK4 degrader led to the identification of BLU-448, with minimal activity against CDK6 for treating HR+/HER2- breast cancer.

Epirium Bio Inc. has developed a series of small-molecule 15-PGDH inhibitors, the phase II-ready MF-300 and preclinical candidate MF-1305, as potential therapeutics for inflammatory bowel disease (IBD).