Skyhawk Therapeutics has reported positive nine-month interim results from its Phase 1 study of SKY-0515, an investigational oral small-molecule RNA modulator for Huntington’s disease (HD).
The company also announced a global expansion of its Phase 2/3 FALCON-HD trial, with more than 90 patients already dosed.
Strong biomarker reductions observed
Treatment with SKY-0515 demonstrated dose-dependent target engagement and meaningful biomarker reductions:
- 62% reduction in blood mutant huntingtin (mHTT) protein at 9 mg
- 26% reduction in PMS1 mRNA at 9 mg
- Excellent central nervous system exposure
- Generally safe and well tolerated across doses
PMS1 is a key driver of somatic CAG repeat expansion and HD disease progression. Reducing both mHTT and PMS1 addresses two major pathogenic mechanisms.
Signals of potential clinical benefit
Patients in Part C of the Phase 1 trial showed improvement from baseline in the Composite Unified Huntington’s Disease Rating Scale (cUHDRS) at:
- 3 months
- 6 months
- 9 months
At nine months:
- SKY-0515 pooled analysis: +0.64 point improvement
- Expected natural history: –0.73 point worsening
This suggests a deviation from typical disease progression.
Expert perspective
Professor Ed Wild (University College London) noted that SKY-0515 has achieved the greatest mHTT reduction tested to date in patients and combines huntingtin lowering with PMS1 suppression, offering a potentially powerful disease-modifying approach.
Skyhawk’s R&D leadership emphasized that strong biomarker activity alongside favorable safety supports SKY-0515’s potential as a best-in-class therapy.
About SKY-0515
- Oral small-molecule RNA modulator
- Developed using Skyhawk’s SKYSTAR® RNA modulation platform
- Designed to reduce both HTT and PMS1 protein levels
- Skyhawk’s first clinical-stage program
Global expansion of FALCON-HD Phase 2/3 trial
The ongoing FALCON-HD study is now expanding worldwide:
- 120 participants in Australia and New Zealand
- ~400 participants across more than 40 global sites
- Once-daily oral dosing
- Treatment duration of at least 12 months
- Evaluates pharmacodynamics, safety, and efficacy
The trial targets patients with stage 2 and early stage 3 HD.
Unmet need in Huntington’s disease
- Over 40,000 symptomatic patients in the United States
- Hundreds of thousands affected worldwide
- No approved disease-modifying therapies currently available
If confirmed in placebo-controlled trials, SKY-0515 could represent a major step toward altering the course of HD.
