#USA #Boston #Huntington's Disease #Skyhawk Therapeutics #SKY-0515

Skyhawk Therapeutics Reports Promising 12-Month Results

Skyhawk Therapeutics, a clinical-stage biotechnology company, recently announced promising findings related to its investigational drug, SKY-0515, aimed at treating Huntington's disease. This announcement was made during the European Academy of Neurology Congress held on July 1, 2026. The results focus on the twelve-month data of the clinical trial, specifically the subcomponents of the Clinical Unified Huntington's Disease Rating Scale (cUHDRS).

The results indicated positive and consistent trends in patients treated with SKY-0515 across all four subcomponents of the cUHDRS, which includes: total functional capacity (TFC), total motor score (TMS), symbol digit modalities test (SDMT), and Stroop word reading test (SWRT).

One of the notable findings from the twelve-month period was an average favorable change in TFC, showing a slight improvement (+0.07) compared to the baseline, while propensity score-weighted analyses suggested a decline of -0.87 points in natural disease progression. Notably, participants on SKY-0515 also experienced improvements in motor score (-2.00) compared to the expected decline of 2.21 points based on previous longitudinal studies.

Additionally, the cognitive assessments through SDMT revealed a stabilization with a minor negative change (-0.19) when matched against the expected decline of -1.78 points. Conversely, the Stroop test showed a robust positive change of +3.44, in stark contrast to the anticipated decline of -3.13 points among untreated participants.

Skyhawk also revealed data from clinician and patient global impressions (CGI and PGI), demonstrating that at the twelve-month mark, neither clinicians nor patients reported progression of the disease. In fact, 65% of participants and 50% of clinicians noted a perceived improvement in the health status of participants, contrary to expectations for significant disease worsening over the same timeframe.

SKY-0515 treatment led to significant reductions in the mutant huntingtin protein (mHTT) levels in blood by up to 69% and reductions of PMS1 mRNA by as much as 26%. The mutant huntingtin protein plays a pivotal role in the pathology of Huntington's disease, while PMS1 has been implicated in CAG repeat expansion associated with disease progression.

Sergey Paushkin, Skyhawk's Chief Development Officer, expressed enthusiasm over the promising outcomes, emphasizing the importance of the improvements in functional and motor assessments, as well as cognitive tests. He articulated that these results reinforce the potential of SKY-0515 to be an easily administered oral treatment that genuinely benefits patients suffering from Huntington’s disease.

SKY-0515 has shown excellent CNS exposure and appears safe and well-tolerated across all dosage levels explored in the study, which included more than 175 participants across five countries. This provides hope for individuals afflicted with Huntington’s disease, a rare neurodegenerative disorder impacting over 40,000 symptomatic patients in the United States alone, with no existing treatment approved to halt or reverse its progression.

The drug SKY-0515 is an oral small molecule that was developed using Skyhawk’s proprietary SKYSTAR® platform, which modifies RNA splicing for therapeutic purposes. Alongside SKY-0515, the SKYSTAR platform has yielded several other innovative treatments targeting rare neurological disorders that previously lacked disease-modifying therapies. Looking forward, Skyhawk anticipates launching additional clinical development programs by the end of 2027.

Clinical Trial Overview

The Phase 1/2 clinical trial of SKY-0515 aimed to assess safety, tolerability, pharmacokinetics, and pharmacodynamics in both healthy volunteers and early-stage Huntington’s patients, evaluating several biomarkers including mHTT and PMS1 levels, alongside efficacy measures such as cUHDRS and its subcomponents.

Overall, this positive data from Skyhawk Therapeutics signifies a hopeful advancement in Huntington’s disease treatment and presents a potential therapeutic option for patients urgently awaiting breakthroughs in care for this devastating condition.