Skyhawk Therapeutics has achieved a significant milestone in Huntington's disease research by dosing the first patient in its Phase 2/3 FALCON-HD trial of SKY-0515, an investigational oral RNA splicing modulator. The clinical-stage biotechnology company announced that initial dosing took place at Flinders Medical Centre in Adelaide, Australia, marking the advancement of a potentially disease-modifying therapy for this devastating neurodegenerative condition.
Novel Dual-Target Approach Shows Promise
SKY-0515 represents a unique therapeutic approach, designed to reduce the production of both huntingtin (HTT) and PMS1 proteins—two key drivers of Huntington's disease pathology. This dual-targeting mechanism distinguishes the compound from other investigational therapies that focus solely on huntingtin reduction.
"SKY-0515's unique ability to reduce both HTT and PMS1 could meaningfully enhance therapeutic impact beyond that of lowering HTT alone," said Ed Wild, professor of neurology at the University College London.
The compound demonstrated robust efficacy in Phase 1 studies, achieving dose-dependent HTT mRNA reduction with an average of 72% lowering at the highest dose tested in healthy volunteers. The treatment was generally well tolerated across all doses, providing a favorable safety profile that supported advancement to the current Phase 2/3 trial.
Accelerated Development Timeline
The development program has progressed rapidly, with the Phase 1 trial in Huntington's disease patients completing enrollment ahead of schedule. The patient study, which began in January 2025, reached full enrollment by March 2025, demonstrating strong interest from the patient community and clinical investigators.
"Dosing the first patient in our FALCON-HD trial marks a significant milestone in our mission to develop a disease-modifying therapy for Huntington's patients," said Bill Haney, Founder and Chief Executive Officer of Skyhawk Therapeutics. "Building on our compelling Phase 1 data, we are eager to assess SKY-0515's potential to make a meaningful difference in the lives of patients affected by this devastating condition."
Comprehensive Phase 2/3 Trial Design
FALCON-HD (NCT06873334) is a randomized, double-blind, placebo-controlled, dose-ranging study designed to evaluate the pharmacodynamics, safety, and efficacy of SKY-0515 in participants with Stage 2 and early Stage 3 Huntington's disease. The trial plans to enroll 120 subjects across 10 sites in Australia and New Zealand.
Eligible patients will receive once-daily oral doses of SKY-0515 at one of three dose levels, or placebo, for a treatment period of at least 12 months. The study aims to assess the compound's potential to modulate RNA splicing and reduce the production of huntingtin and PMS1 proteins, which are implicated in Huntington's disease pathology.
Addressing Critical Unmet Medical Need
The advancement of SKY-0515 addresses a significant gap in Huntington's disease treatment options. Dr. Karyn Boundy, FRACP, Neurologist and Principal Investigator at Flinders Medical Centre, emphasized the importance of this development: "Given the lack of approved disease-modifying treatments for Huntington's disease, we are hopeful that SKY-0515 could offer a new therapeutic option for patients."
Proprietary RNA Splicing Platform
SKY-0515 was developed through Skyhawk's proprietary drug discovery platform, which assesses, identifies, and tests RNA splicing targets and small molecules across various therapeutic areas. The company has established collaborations with multiple pharmaceutical partners leveraging this platform across neurodegenerative disease, autoimmune disease, and oncology applications.
The oral small molecule RNA splicing modulator represents a novel approach to targeting the underlying molecular mechanisms of Huntington's disease, potentially offering advantages in terms of patient compliance and therapeutic accessibility compared to other investigational approaches requiring more complex administration methods.
