Halia Therapeutics Dosed its First Patient in Phase 2a Clinical Trial of HT-6184, a First-in-Class NLRP3-Inhibitor, for the Treatment of Lower-Risk Myelodysplastic Syndromes
December 13, 2023

LEHI, Utah, Dec. 13, 2023 /PRNewswire/ — Halia Therapeutics, a clinical-stage biopharmaceutical company pioneering a novel class of small molecule medications designed to combat inflammation, today announced the dosing of the first patient in Phase 2a clinical trial of HT-6184 its lead candidate, for evaluating the treatment of lower-risk myelodysplastic syndromes (LR-MDS). HT-6184 is a selective and orally bioavailable first-in-class inhibitor of NLRP3/NEK7 inflammasome, a main driver of inflammatory diseases, as well as hematologic and other malignancies. 

Myelodysplastic syndromes are a group of cancers in which the bone marrow produces underdeveloped (immature) cells that are abnormal in size, shape, or appearance, which are called “dysplastic. This leads to a reduced number of healthy blood cells, which can result in multiple complications, including but not limited to anemia, recurrent infections, and progression to cancer. The trial will evaluate the safety and activity of HT-6184 in up to 40 patients with LR-MDS and will be conducted at multiple sites across India. The study will measure the rate of hematological improvement, including transfusion dependency and changes in hemoglobin levels as primary endpoints for the study. Secondary endpoints will further assess the effect of HT-6184 on biomarkers of inflammasome activation in MDS and the changes in clone size of somatic gene mutations. The trial is expected to be completed by Q4 2025.

“The dosing of the first patient in our Phase 2 trial of HT-6184 marks a significant milestone for Halia in further evaluating the potential of targeting the NLRP3 inflammasome to treat a wide spectrum of immunological and inflammatory diseases,” said Margit M. Janát-Amsbury, MD, Ph.D., Chief Medical Officer of Halia Therapeutics.  “The recent positive results of our Phase I trial investigating HT-6184 are extremely encouraging and highlight the functional activity of HT-6184 in being able to reduce inflammatory cytokines. As we move into this next stage of clinical testing, we look forward to assessing the potential benefit of our inflammasome inhibitor for MDS patients, as well as for other patients who suffer from inflammation-related diseases.”

Halia recently announced Phase I trial results evaluating HT-6184, which was shown to be safe, well tolerated and to significantly reduce NLRP3-inflammatory cytokines in healthy volunteers. 

About NLRP3
NLRP3, an innate immune sensor, is activated in response to various pathogenic and sterile stimuli. Activation of NLRP3 triggers the release of the pro-inflammatory cytokines IL-1β and IL-18 and induces a lytic cell death process called pyroptosis. These processes lead to systemic chronic inflammation. Halia’s therapeutic inhibition of NLRP3 prevents the formation of the NLRP3 inflammasome and promotes its disassembly once formed, thereby inhibiting the production and release of IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome is thought to drive the onset and progression of many conditions, including fibrotic, dermatological, and auto-inflammatory diseases. Significant neurodegenerative and neuroinflammatory disorders such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis are also driven by NLRP3 activation. Notably, in recent years, NLRP3 has been discovered and is gaining significance as one of the key biological drivers of ineffective hematopoiesis and inflammation in MDS.

About HT-6184
HT-6184 represents an innovative approach as it is the first drug candidate to target the protein NEK7 through an allosteric mechanism. NEK7 is an essential component of the NLRP3 inflammasome and is critical for its assembly and the maintenance of NLRP3 activity. In preclinical models, Halia has shown that inhibiting the ability of NEK7 to bind to NLRP3 leads to a disruption in the formation of the NLRP3 inflammasome complex, thereby inhibiting the signaling from the inflammasome and reducing the inflammatory response. Preclinical models also showed that in addition to disrupting the formation of the NLRP3 inflammasome, HT-6184 promotes the disassembly of the inflammasome once activated.

About Halia Therapeutics, Inc.
Halia Therapeutics is discovering and developing a pipeline of novel therapeutics to improve patients’ lives with chronic inflammatory disorders and neurodegenerative diseases, with its initial programs targeting NEK7 and LRRK2. Halia’s lead candidate, HT-6184, a novel NEK7/NLRP3 inhibitor, has completed a Phase 1 study (NCT05447546) evaluating the safety and tolerability of HT-6184 when administered as single or multiple oral doses at escalating dose levels in healthy volunteer subjects. The company is headquartered in Lehi, Utah. For more info, visit www.haliatx.com or follow us on LinkedIn and Twitter (X).

Company Contact: James Dye