LEHI, Utah, Nov. 29, 2023 /PRNewswire/ — Halia Therapeutics, a clinical-stage biopharmaceutical company pioneering a novel class of small molecule medications designed to combat inflammation, today announced positive results following the successful completion of a Phase 1 clinical trial for its leading candidate, HT-6184, a highly selective and orally bioavailable inhibitor of NLRP3/NEK7, a main driver of immune-inflammatory diseases, hematologic malignancies, and even cancer.
“We are encouraged by the results of this study that indicate our inflammasome inhibitor, HT-6184, is overall well tolerated and reduces inflammatory cytokines associated with the NLRP3 inflammasome,” said Dr. Dave J. Bearss, CEO and President of Halia Therapeutics. “Chronic inflammation caused by aberrant inflammasome activation has been linked to various illnesses, and the results of this study show promise in inhibiting chronic inflammation by disrupting the inflammasome’s assembly process. The outcome of this study validates our approach to combat inflammation and paves the way for further clinical studies.”
The Phase 1 trial, registered under NCT05447546, was a randomized, placebo-controlled, single-center study conducted with healthy volunteers. It consisted of both single ascending dose (SAD) and multiple ascending dose (MAD) escalation phases, with a focus on assessing the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of HT-6184.
Key Details of the Study:
- The SAD and MAD segments of the study each involved 32 healthy volunteers, with 8 subjects in each cohort receiving either HT-6184 or a placebo (6 received HT-6184, 2 received a placebo in each cohort).
- In the SAD phase, HT-6184 was administered at doses ranging from 1 mg to 4 mg in single mg increments.
- In the MAD phase, the same doses of HT-6184 were given once daily (QD) for 5 days a week over 2 weeks, with dosing occurring on Days 1-5 and Days 8-12.
- Pharmacodynamic effects of HT-6184 dosing was explored and a relationship between exposure level of the compound and modulation of inflammatory and immune signaling was observed.
Safety and Tolerability Results:
- In the SAD phase, 12.5% of the subjects treated with HT-6184 experienced treatment-related treatment-emergent adverse events (TR-TEAE) across all dose levels, compared to 0% in the placebo group. No severe adverse events (SAE) occurred, and no subjects withdrew from the study due to TEAE.
- In the MAD phase, 20.8% of subjects treated with HT-6184 experienced TR-TEAE across all dose levels, compared to 25% in the placebo group. No severe AEs were observed, but two subjects at the highest dose level in the MAD phase withdrew due to TEAE.
- Despite the very low doses tested, HT-6184 demonstrated potent pharmacodynamic effects in ex-vivo whole blood assays, showing over 90% suppression of multiple NLRP3-mediated cytokines and chemokines in healthy volunteer samples.
Overall, the study results indicate that HT-6184 was well-tolerated up to 4 mg as a single dose and up to 4 mg as multiple doses taken over 2 weeks. Importantly, there was no increased risk of treatment-related infections observed. In addition, HT-6184 was shown to significantly reduce NLP3-inflammatory cytokines. These positive findings pave the way for HT-6184 to advance to initial proof-of-concept Phase 2 studies involving different patient populations. Halia is actively pursuing Phase 2 studies with HT-6184 in post-procedural inflammatory pain response, myelodysplastic syndrome, Alzheimer’s Disease, and autoimmune disorders.
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 neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis are also driven by NLRP3 activation.
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).