Skyhawk Therapeutics Announces First Patient Dosed in Phase 2/3 FALCON-HD Trial of SKY-0515 for Huntington's Disease

SKY-0515 is an oral small molecule designed to reduce the production of both huntingtin (HTT) and PMS1 proteins—two key drivers of HD pathology. Initiation of the FALCON-HD trial follows promising Phase 1 results demonstrating up to 72% reduction in HTT mRNA in healthy volunteers. The SKY-0515 Phase 1 trial in patients with Huntington's disease reached full enrollment ahead of schedule

BOSTON, June 17, 2025 /PRNewswire/ -- Skyhawk Therapeutics, Inc., a clinical-stage biotechnology company developing novel small molecule therapies designed to modulate critical RNA targets, today announced that the first patient has been dosed in its Phase 2/3 FALCON-HD trial evaluating SKY-0515, an investigational oral RNA splicing modulator for the treatment of Huntington's disease (HD).

SKY-0515 is designed to reduce the production of both HTT and PMS1 proteins—two key drivers of HD pathology. In a Phase 1 study in healthy volunteers, SKY-0515 demonstrated dose-dependent HTT mRNA reduction, achieving an average of 72% lowering at the highest dose tested. The compound was generally well tolerated across all doses. Additionally, the Company's Phase 1 trial in HD patients, which began in January 2025, completed enrollment ahead of schedule in March 2025.

"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."

FALCON-HD is a Phase 2/3 randomized, double-blind, placebo-controlled, dose ranging study to evaluate the pharmacodynamics, safety, and efficacy of SKY-0515 in participants with Stage 2 and early Stage 3 HD. The trial includes multiple sites across Australia and New Zealand. The initial dosing took place at Flinders Medical Centre in Adelaide, Australia.

"We are pleased to participate in this important clinical trial and to have dosed the first patient here at Flinders," said Dr. Karyn Boundy, FRACP, Neurologist, Principal Investigator at Flinders Medical Centre. "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."

"As Skyhawk kicks off their Phase 2/3 FALCON-HD trial in Australia and New Zealand, the international Huntington's community looks forward to expansion worldwide," said Ed Wild, professor of neurology at the University College London. "SKY-0515's unique ability to reduce both HTT and PMS1 could meaningfully enhance therapeutic impact beyond that of lowering HTT alone."

FALCON-HD (NCT06873334) is a Phase 2/3 randomized, double-blind, placebo-controlled, dose ranging study to evaluate the pharmacodynamics, safety, and efficacy of SKY-0515 in participants with Stage 2 and early Stage 3 HD. The trial plans to enroll 120 subjects across 10 sites in Australia and New Zealand. Eligible patients will receive a once-daily oral dose of SKY-0515 at one of three dose levels, or placebo, for a treatment period of at least 12 months. The trial aims to assess the potential of SKY-0515 to modulate RNA splicing and reduce the production of huntingtin (HTT) and PMS1 proteins, which are implicated in the pathology of Huntington's disease.

Additional information about FALCON-HD, including participating sites and eligibility criteria, can be found at ClinicalTrials.gov and www.FALCON-HD.com.

About SKY-0515

SKY-0515 is an orally administered small molecule RNA splicing modulator developed through Skyhawk's proprietary platform. It is designed to reduce production of both huntingtin (HTT) and PMS1 proteins, two key contributors to Huntington's disease. SKY-0515 has shown robust, dose-dependent HTT mRNA reduction—up to 72%—in healthy volunteer studies, with favorable safety and tolerability. SKY-0515 is currently being evaluated in a Phase 2/3 clinical trial.

About Skyhawk Therapeutics

Skyhawk Therapeutics is a clinical-stage biotechnology company focused on the discovery and development of novel small molecule therapies designed to modulate critical RNA targets and revolutionize patient treatment for some of the world's most intractable diseases. Skyhawk's discovery expertise is rooted in its proprietary drug discovery platform, which assesses, identifies, and tests RNA splicing targets and small molecules across a broad range of therapeutic areas and disease states. Skyhawk has built collaborations with multiple pharma partners that leverage Skyhawk's novel platform across disease areas including neurodegenerative disease, autoimmune disease, and oncology. For more information visit www.skyhawktx.com. 

About Skyhawk Therapeutics

Skyhawk Therapeutics is a clinical-stage biotechnology company focused on the discovery and development of novel small molecule therapies designed to modulate critical RNA targets and revolutionize patient treatment for some of the world's most intractable diseases. Skyhawk's discovery expertise is rooted in its proprietary drug discovery platform, which assesses, identifies, and tests RNA splicing targets and small molecules across a broad range of therapeutic areas and disease states. Skyhawk has built collaborations with multiple pharma partners that leverage Skyhawk's novel platform across disease areas including neurodegenerative disease, autoimmune disease, and oncology. For more information visit www.skyhawktx.com.  

Skyhawk Company Contact

Kyle Dow, VP Corporate Development

kyle.dow@skyhawktx.com  

SOURCE Skyhawk Therapeutics, Inc.

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