Lehi, Utah-based Halia Therapeutics, Inc. announced receipt of US FDA Fast Track Designation for ofirnoflast (HT-6184), a first-in-class oral allosteric modulator of NEK7, for the treatment of adult patients with lower-risk myelodysplastic syndromes (LR-MDS). The designation, which enables more frequent interactions with the US FDA and confers eligibility for Rolling Review, Priority Review, and Accelerated Approval if relevant criteria are met, follows final Phase II data presented at the European Hematology Association (EHA) 2026 Congress in Stockholm on June 12, 2026. Ofirnoflast had previously received Orphan Drug Designation from the US FDA for MDS in October 2025.
Ofirnoflast is an oral NEK7 modulator designed to inhibit NLRP3 inflammasome activation, an inflammatory pathway implicated in ineffective hematopoiesis in LR-MDS. In a Phase II study of 37 ESA-refractory or ESA-ineligible LR-MDS patients, ofirnoflast achieved a 67% hematologic improvement rate among evaluable patients.
Detailed data from the study were disclosed in detail ahead of an EHA2026 oral presentation. Among the 18 transfusion-dependent patients, 10 (56%) achieved RBC transfusion independence for ≥8 weeks, with a median duration of 28 weeks; 39% sustained independence for ≥16 weeks. Among 12 non-transfusion-dependent patients, 9 (75%) achieved HI-E. Treatment-related adverse events were predominantly low grade, with no treatment-related serious adverse events reported. Activity was mutation-agnostic, observed across WHO MDS subtypes and irrespective of SF3B1 mutation or del(5q) status.
LR-MDS is characterized by chronic cytopenias, particularly anemia, that impose a substantial transfusion burden on a predominantly elderly patient population. After ESA failure or ineligibility, options narrow considerably. Luspatercept (Reblozyl), an erythroid maturation agent approved by the US FDA in 2020 for transfusion-dependent LR-MDS with ring sideroblasts, demonstrated transfusion independence rates of approximately 38% in the MEDALIST trial. Lenalidomide remains the standard for del(5q) MDS. Outside these defined subgroups, patients with ESA-refractory disease and non-del(5q) or non-SF3B1 mutated disease have limited approved options.