Skyhawk Therapeutics, Inc. announced encouraging results from its first interim analysis of the Phase 1 clinical trial for SKY-0515, an experimental treatment for Huntington’s disease (HD). The findings reveal that patients receiving SKY-0515 exhibited a dose-dependent reduction in mutant huntingtin (mHTT) protein levels, achieving a significant 62% decrease at the 9 mg daily dose by Day 84 of the trial.
In addition to the notable reduction in mHTT protein, other important outcomes were observed, including dose-dependent decreases in PMS1 mRNA and excellent central nervous system penetration. The overall safety profile of SKY-0515 has been favorable across both dose levels tested, indicating a promising path for further clinical development.
Clinical Insights and Expert Opinions
Professor Ed Wild, a neurologist at University College London, commented on the results, stating, “SKY-0515 is reducing mHTT protein to the most impressive extent we’ve seen so far in patients, and crucially the clinical and biomarker data show no safety concerns so far at any dose tested.” He emphasized the importance of the substantial reduction in PMS1, which he believes could enhance the treatment’s efficacy against Huntington’s disease by addressing two of its core pathogenic mechanisms.
Sergey Paushkin, Head of Research and Development at Skyhawk Therapeutics, also highlighted the significance of the interim data, stating, “The strength of SKY-0515’s biomarker response after just 84 days of treatment underscores its potential as a transformative therapy for HD.” He described the results as an important milestone for SKY-0515, showcasing the capabilities of Skyhawk’s platform to deliver innovative small molecules for diseases that currently lack approved therapies.
Ongoing Trials and Future Developments
The Phase 1 clinical trial consists of three parts, with Parts A and B focusing on healthy volunteers and Part C assessing the drug’s effects on individuals with early-stage Huntington’s disease. This latter part is a double-blind, placebo-controlled study that evaluates two dose levels of SKY-0515 over 84 days, followed by a 12-month extension during which all participants will receive either the low or high dose of the drug.
The enrollment for Part C is now complete, and topline data from the blinded active treatment extension is anticipated in mid-2026. In parallel, Skyhawk is conducting a Phase 2/3 clinical trial known as FALCON-HD, which includes 120 participants with Stage 2 and early Stage 3 HD across ten sites in Australia and New Zealand. This trial aims to explore the safety, pharmacodynamics, and potential efficacy of SKY-0515 over a treatment period of at least 12 months.
Huntington’s disease, a hereditary neurodegenerative disorder, currently affects over 40,000 symptomatic patients in the United States alone, with hundreds of thousands more estimated to be impacted globally. Presently, there are no approved treatments that slow or halt the progression of this devastating condition.
SKY-0515 is designed to be an orally administered small molecule RNA splicing modifier, developed using Skyhawk’s proprietary SKYSTAR® platform. The drug aims to reduce both HTT protein and PMS1 protein, which are implicated in the pathology of Huntington’s disease. Skyhawk Therapeutics anticipates advancing several additional novel therapies targeting rare neurological diseases into clinical trials by the end of 2027, with the next drug expected to enter trials in mid-2026.
For further details about ongoing studies, including eligibility criteria and participating sites, interested parties can visit ClinicalTrials.gov and www.FALCON-HD.com.
