Dr Sallman on Next Steps for Ofirnoflast in Lower-Risk MDS

If we can hold up with even a 40% transfusion independence rate, this is a game changer, because [ofirnoflast] is an oral option before hypomethylating agents, where patients really have quite limited options.

David Sallman, MD, an associate member in the Department of Malignant Hematology at Moffitt Cancer Center, discussed final results from a phase 2a trial (NCT07052006) evaluating the first-in-class allosteric NEK7 inhibitor ofirnoflast (HT-6184) in patients with erythropoiesis-stimulating agent (ESA)–refractory lower-risk myelodysplastic syndrome (MDS), which were presented at the 2026 Society of Hematologic Oncology (SOHO) Annual Meeting, and outlined next steps toward a phase 3 trial.

Sallman said before a phase 3 study is conducted, another phase 2 trial (NCT07738510) will serve as dose optimization evaluating 2-mg and 3-mg daily doses to identify the better efficacy and tolerability balance. Notably, this subsequent trial features broadened eligibility beyond isolated ESA failure to patients with 1 to 3 prior lines of therapy, including those who received luspatercept-aamt (Reblozyl), could still yield a transfusion independence rate near 40%.

This study could inform a pivotal phase 3 trial, Sallman said, in which he would replicate the phase 2 design and target a 16-week transfusion independence rate above 30%, adding that positive phase 2 findings would make a phase 3 trial in the same population a logical next step.

Sallman discussed combination strategies, noting ofirnoflast, luspatercept, ESAs, and hypomethylating agents act through distinct, non-overlapping mechanisms that could support a basket trial testing different combinations. Patients with baseline erythropoietin levels above 500 mU/mL or high transfusion burden—subgroups that may respond less robustly to ESAs—could be candidates for such approaches, he said.

Sallman said the inflammasome-targeting may potentially improve quality of life, though he suggested ofirnoflast may have a greater role earlier in disease course, before excess blasts or transformation to acute myeloid leukemia occur.