On December 19, 2024 Halia Therapeutics reported the second stage of a phase 2 trial exploring the first-in-class allosteric NEK7/NLRP3 inflammasome inhibitor HT-6184 for the treatment of patients with lower-risk myelodysplastic syndromes (LR-MDS) is launching following positive topline data from the initial cohort of 18 patients (Press release, Halia Therapeutics, DEC 19, 2024, View Source [SID1234649214]).
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Among the 18 patients with LR-MDS, a hematological improvement-erythroid response to HT-6184 was seen after 16 weeks of monotherapy. This exceeded the preset requirement of at least 3 responders.
The study will now advance to its second stage expansion, which will enroll an additional 8 to 10 patients.
"The high frequency of erythroid response following treatment with HT-6184 validates the key importance of the NLRP3 inflammasome and myddosome pathways as pathogenetic drivers of ineffective hematopoiesis in MDS, offering the prospect of a safe and effective oral therapeutic for LR-MDS patients," said Alan List, MD, Halia Therapeutics SAB Member, in a press release.
HT-6184 is a new drug candidate that works by targeting the protein NEK7 through an allosteric mechanism. Preclinically, it has been shown that inhibiting NEK7’s binding ability to NLRP3 disrupts inflammasome signaling and reduces the inflammatory response. In unpublished data from Halia Therapeutics, HT-6184 has also been shown to prevent the formation of the NLRP3 inflammasome and promotes its disassembly once activated.
In this phase 2 trial, investigators are using a Simon’s minimax two-stage design to evaluate HT-6184’s safety and efficacy in up to 40 patients. The study is ongoing across multiple clinical sites in India.
Hematologic improvements, including transfusion dependency and changes in hemoglobin levels, are the study’s primary end points. Secondary end points of the trial include evaluating HT-6184’s impact on biomarkers of inflammasome activation in MDS and the size of somatic gene mutation clones.
The study’s estimated completion date is by the end of Q2 of 2025. If positive, the results can support the agent’s continued clinical development and potential regulatory submission.
A phase 1 study of HT-6184 (NCT05447546) previously evaluated the agent’s safety and tolerability when given to patients as single or multiple oral doses at escalating levels. Now, a phase 2 trial is ongoing to study the efficacy of HT-6184 in the treatment of patients with LR-MDS, and another phase 2 study is assessing its impact on post-procedure diagnostic biomarkers of inflammation and pain (NCT06241742).
"This trial represents a significant step forward in addressing the unmet needs of patients with LR-MDS," said David J. Bearss, PhD, president and chief executive officer of Halia Therapeutics, in a press release. "By targeting the underlying inflammatory signaling driving this condition, HT-6184 aims to transform treatment outcomes and improve quality of life for patients who currently face limited options."