Skyhawk Reports Positive 9-Month Interim Data for SKY-0515 in Huntington’s Disease, Expands Global Phase 2/3 Trial

Skyhawk Reports Positive 9-Month Interim Data for SKY-0515 in Huntington’s Disease, Expands Global Phase 2/3 Trial

By, Admin 29 January 2026

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.

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