Boston, Massachusetts, USA, November 5, 2026
Skyhawk Therapeutics, Inc. has announced that the first patients in the United States have received doses of SKY-0515, an investigational oral therapy being evaluated in the global pivotal FALCON-HD clinical development program for Huntington’s disease (HD). The milestone marks an important expansion of the company’s international clinical research activities and brings the investigational treatment to additional patients and clinical research centers across the United States. Initial U.S. dosing began at the CenExel Movement Disorder Center in Colorado, while additional participating institutions, including Beth Israel Deaconess Medical Center, are expected to begin enrolling and dosing patients. According to the company, more than 50,000 doses of SKY-0515 have been administered across more than 30 clinical study sites in 10 countries. The development program is designed to evaluate the safety, pharmacodynamics and potential clinical benefits of SKY-0515 in individuals living with Huntington’s disease. This milestone is particularly significant because there are currently no approved disease-modifying treatments demonstrated to slow or stop the underlying progression of Huntington’s disease. Skyhawk aims to develop a once-daily oral treatment that targets important biological mechanisms associated with disease progression, potentially offering a new therapeutic approach for affected patients.
SKY-0515 Targets Mutant Huntingtin and PMS1 Proteins
SKY-0515 is an investigational small-molecule RNA splicing modifier designed to influence the expression of two important biological targets associated with Huntington’s disease: mutant huntingtin (mHTT) and PMS1. Huntington’s disease is an inherited neurodegenerative disorder caused by an expanded CAG repeat sequence in the huntingtin gene. This genetic alteration results in the production of abnormal mutant huntingtin protein, which contributes to progressive damage in nerve cells. The disease can affect movement, cognitive abilities, behavior and everyday functioning, with symptoms generally worsening over time. SKY-0515 is designed to reduce the production of mutant huntingtin protein by modifying RNA splicing. In addition, the treatment targets PMS1, a protein associated with somatic CAG repeat expansion, a biological process implicated in Huntington’s disease progression. By addressing these two mechanisms, the investigational treatment aims to influence both mutant protein production and an important genetic instability pathway. SKY-0515 is administered orally once daily, which may offer a convenient treatment approach compared with therapies requiring more complex administration procedures. The candidate was developed using Skyhawk’s proprietary SKYSTAR® RNA-modulating platform, which supports the discovery of small-molecule therapies designed to regulate RNA expression in serious neurological and other diseases.
Global FALCON-HD Program Evaluates Safety and Efficacy
The FALCON-HD pivotal development program comprises two randomized, double-blind, placebo-controlled, dose-ranging clinical studies designed to evaluate the pharmacodynamics, safety and efficacy of SKY-0515. Eligible participants receive one of three once-daily oral dose levels or placebo. The program includes FALCON-HD 004-ANZ and FALCON-HD 004-WW, covering Australia and New Zealand as well as a broader international clinical research network. The 004-ANZ study completed enrollment with 144 participants diagnosed with Stage 2 and Stage 3 Huntington’s disease across clinical sites in Australia and New Zealand. Meanwhile, the worldwide 004-WW study is actively recruiting participants across more than 40 planned clinical research sites. The expansion into the United States is expected to strengthen the international study network and provide additional opportunities for eligible patients to participate. The clinical program will assess treatment-related changes in disease biomarkers and clinical measures, helping researchers evaluate whether SKY-0515 can produce meaningful biological and functional benefits. Its randomized and placebo-controlled design is intended to provide more robust evidence regarding the investigational treatment’s performance and safety.
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Skyhawk Advances Development of Potential Disease-Modifying Therapy
The first U.S. patient dosing milestone builds on earlier clinical findings from Skyhawk’s Phase 1/2 program. In September 2026, the company reported 15-month results showing favorable changes in the Composite Unified Huntington’s Disease Rating Scale (cUHDRS) compared with an external natural-history control group. The company also reported reductions in mutant huntingtin protein and PMS1 mRNA at the evaluated doses. These earlier findings provided additional support for advancing SKY-0515 into larger pivotal studies. However, results from early-stage investigations and comparisons with external control groups do not establish definitive clinical efficacy. The ongoing FALCON-HD studies will be important in determining whether the treatment can consistently demonstrate meaningful benefits in a controlled clinical setting. Skyhawk Therapeutics, headquartered in Boston, Massachusetts, focuses on developing RNA-modulating small molecules for serious neurological and other diseases. The expansion of FALCON-HD into the United States represents an important step in the clinical development of SKY-0515 and the search for disease-modifying treatment options for Huntington’s disease. Further clinical evidence will be essential to establish its long-term safety, effectiveness and potential regulatory pathway.
Source: Skyhawk Therapeutics press release
