Halia Therapeutics has announced the dosing of the first healthy volunteer in a Phase 1 clinical trial of HT-4253, a novel oral LRRK2 inhibitor being developed as a potential treatment for Alzheimer's Disease. The study, a first-in-human trial, aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of HT-4253.
The Phase 1 trial (NCT06537817) employs a randomized, placebo-controlled, double-blind design, utilizing single ascending dose (SAD) and multiple ascending dose (MAD) formats. The primary objective is to assess the drug's ability to inhibit LRRK2, a critical enzyme implicated in neuroinflammation.
Rationale Behind LRRK2 Inhibition
Recent genetic studies have identified variants in the Rab10 gene that appear to protect individuals carrying the APOE4 genotype, a significant risk factor for Alzheimer's disease. These protective variants inhibit Rab10, a protein activated by LRRK2, leading to reduced neuroinflammation and neuroprotection. HT-4253 is designed to mimic these Rab10 variants by blocking LRRK2, thereby preventing Rab10 activation and potentially preventing or delaying the onset of Alzheimer's in APOE4 carriers.
HT-4253: A Potential Disease-Modifying Agent
HT-4253 is an orally administered small molecule with demonstrated brain penetration. By targeting LRRK2, a key mediator of neuroinflammation, HT-4253 aims to address the chronic brain inflammation that drives neurodegenerative diseases like Parkinson's and Alzheimer's. Preclinical studies by Halia scientists suggest that LRRK2 plays a crucial role in regulating neuroinflammation, making its inhibition a promising therapeutic strategy.
Halia Therapeutics' Broader Pipeline
Halia Therapeutics is also developing HT-6184, a NEK7/NLRP3 inhibitor, which has completed a Phase I study (NCT05447546) and a Phase II trial assessing its impact on post-procedure diagnostic biomarkers of inflammation and pain (NCT06241742). The company is currently conducting a Phase II trial to evaluate HT-6184's efficacy in treating lower-risk myelodysplastic syndromes (LR-MDS).
"Dosing the first subject in the Phase 1 trial of HT-4253 marks a significant step in the fight against neurodegenerative diseases such as Alzheimer's disease," said Dr. David Bearss, CEO of Halia Therapeutics. "We believe that HT-4253 will provide a groundbreaking treatment option for patients who currently have few choices to prevent or delay Alzheimer's onset, as the drug targets the underlying neuroinflammation linked to causing neurocognitive disease."
