Twelve-Month Results Show Consistent Favorable Trends
Skyhawk Therapeutics, Inc., a clinical-stage biotechnology company developing novel small molecule therapies targeting RNA, has announced twelve-month interim data from its Phase 1/2 clinical trial of SKY-0515, an oral investigational treatment for Huntington's disease (HD). The data, presented at the European Academy of Neurology, showed favorable and consistent trends for participants receiving SKY-0515 across all four components of the composite Unified Huntington's Disease Rating Scale (cUHDRS).
Detailed Subcomponent Results
The cUHDRS subcomponents include Total Functional Capacity (TFC), Total Motor Score (TMS), Symbol Digit Modalities Test (SDMT), and Stroop Word Reading Test (SWRT). At twelve months, participants on SKY-0515 demonstrated a mean change from baseline TFC score of +0.07, compared with an expected worsening of -0.87 points from propensity score-weighted analyses using Enroll-HD natural history datasets. For TMS, the mean change was -2.00 (improvement), versus an expected worsening of 2.21 points. SDMT scores stabilized with a mean change of -0.19, compared to an expected decline of -1.78 points. SWRT scores improved by +3.44, versus an expected worsening of -3.13 points.
Clinician and Patient Global Impression Data
Skyhawk also released Clinician and Patient Global Impression (CGI and PGI) improvement of disease survey data from the interim analysis. Over twelve months, no clinicians or participants assessed any worsening of disease; all participants were rated as either stable or improved. Specifically, 65% of participants and 50% of clinicians reported improvement.
Biomarker and Safety Observations
Treatment with SKY-0515 resulted in dose-dependent reductions in mutant huntingtin (mHTT) protein in blood of up to 69%, as well as reductions in PMS1 mRNA of up to 26%. Mutant huntingtin is the primary protein responsible for HD pathology, while PMS1 is a key driver of somatic CAG repeat expansion associated with disease progression. The company noted that these biomarker changes support the clinical findings.
According to Skyhawk, the twelve-month data represent a significant milestone for the development of SKY-0515 as a potential disease-modifying therapy for Huntington's disease. The company plans to continue the trial and pursue further regulatory discussions.
