HT-6184 (Ofirnoflast): A Novel NEK7/NLRP3 Inflammasome Inhibitor in Clinical Development

1. Executive Summary

HT-6184, also known by its International Nonproprietary Name (INN) Ofirnoflast, is an orally bioavailable, first-in-class small molecule inhibitor that targets the NIMA Related Kinase 7 (NEK7)/NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome axis through a novel allosteric mechanism.[1] Developed by Halia Therapeutics, a clinical-stage biopharmaceutical company, HT-6184 is being investigated for a range of diseases driven by chronic inflammation and neurodegeneration.[1] Halia Therapeutics' approach is reportedly inspired by the concept of "genetic resilience," aiming to develop therapies that mimic naturally occurring protective biological states.[7]

Currently, HT-6184 is in Phase II clinical development across multiple indications. These include Lower-Risk Myelodysplastic Syndromes (LR-MDS), where it aims to improve hematopoiesis by targeting clonal inflammation in the bone marrow [1]; post-procedural inflammation and pain, using a dental surgery model to assess acute anti-inflammatory effects [9]; and anemia, which appears to be primarily investigated within the context of MDS.[8] Furthermore, a Phase IIa trial is planned to evaluate HT-6184 in combination with semaglutide for obesity and Type 2 Diabetes (T2D), targeting metaflammation.[1] Other potential therapeutic areas mentioned include Alzheimer's disease, Acute Myeloid Leukemia (AML), and certain ophthalmological disorders.[7]