BOSTON, Massachusetts, June 30, 2026
Skyhawk Therapeutics has announced encouraging 12-month interim results from its ongoing Phase 1/2 clinical trial evaluating SKY-0515, an investigational oral RNA splicing modifier for the treatment of Huntington’s disease (HD). Presented at the European Academy of Neurology, the latest findings demonstrated favorable and consistent trends across all four components of the composite Unified Huntington’s Disease Rating Scale (cUHDRS), including Total Functional Capacity (TFC), Total Motor Score (TMS), Symbol Digit Modalities Test (SDMT), and Stroop Word Reading Test (SWRT). In addition, clinician and patient assessments revealed that no participants were considered to have experienced disease progression after twelve months, with many reporting measurable improvement. The data further showed substantial reductions in mutant huntingtin (mHTT) protein and PMS1 mRNA, reinforcing the therapeutic potential of SKY-0515 as a disease-modifying treatment for Huntington’s disease. These findings strengthen Skyhawk’s RNA-targeted development strategy and support continued advancement of the company’s pivotal FALCON-HD Phase 2/3 clinical program.
Twelve-Month Data Demonstrates Functional, Motor and Cognitive Benefits
The 12-month interim analysis showed encouraging outcomes across every measured component of the cUHDRS, suggesting that participants receiving SKY-0515 experienced stabilization or improvement in disease progression compared with expected declines observed in natural history datasets. Patients demonstrated a mean improvement in Total Functional Capacity (TFC), while Total Motor Score (TMS) indicated improved motor function relative to expected disease worsening. Cognitive assessments also remained favorable, with Symbol Digit Modalities Test (SDMT) results showing stabilization and Stroop Word Reading Test (SWRT) scores demonstrating measurable improvement.
Importantly, 65% of patients and 50% of clinicians reported improvement, while none reported disease worsening during the twelve-month treatment period. These encouraging clinical observations suggest that SKY-0515 may offer meaningful functional benefits for individuals living with Huntington’s disease, a progressive neurodegenerative disorder that currently has no approved disease-modifying therapy.
RNA-Targeted Therapy Reduces Disease Biomarkers
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Beyond clinical assessments, SKY-0515 demonstrated significant activity against key molecular drivers of Huntington’s disease. Treatment produced dose-dependent reductions of up to 69% in mutant huntingtin (mHTT) protein, the toxic protein responsible for disease pathology, together with reductions of up to 26% in PMS1 mRNA, a genetic factor associated with somatic CAG repeat expansion and disease progression. SKY-0515 is an orally administered small-molecule RNA splicing modifier developed using Skyhawk’s proprietary SKYSTAR® RNA-targeting platform, enabling simultaneous modulation of multiple disease pathways.
The investigational therapy also demonstrated excellent central nervous system exposure while maintaining a favorable safety and tolerability profile across all evaluated dose levels. These combined biomarker and clinical findings strengthen confidence that RNA-targeted therapeutic approaches may provide durable disease-modifying benefits by directly addressing the underlying molecular mechanisms responsible for Huntington’s disease progression.
Positive Results Support Global Phase 2/3 Development
The encouraging interim data further support the advancement of Skyhawk’s global FALCON-HD Phase 2/3 clinical program, designed to evaluate the pharmacodynamics, efficacy, and safety of SKY-0515 in patients with Stage 2 and early Stage 3 Huntington’s disease. The company’s development program has already enrolled more than 175 participants across five countries, with pivotal international studies actively progressing. Huntington’s disease affects more than 40,000 symptomatic individuals in the United States and hundreds of thousands worldwide, creating an urgent need for innovative therapies capable of slowing or halting disease progression.
By combining strong biomarker reductions, encouraging clinical outcome measures, and favorable patient-reported improvements, Skyhawk Therapeutics continues to position SKY-0515 as one of the leading investigational RNA-based therapies for Huntington’s disease. The latest Phase 1/2 findings represent another significant milestone in the company’s mission to develop transformative RNA-modulating medicines for serious neurological disorders while advancing precision therapies capable of addressing diseases with substantial unmet medical needs.
Source: Skyhawk Therapeutics press release
