SKY-0515 for Huntington’s disease

Last updated July 15, 2025, by Andrea Lobo, PhD
Fact-checked by Marta Figueiredo, PhD

What is SKY-0515 for Huntington’s disease?

SKY-0515 is an experimental oral therapy that is being developed by Skyhawk Therapeutics to slow or halt disease progression in people with Huntington’s disease.

Huntington’s is caused by a defect in the HTT gene that consists of excessive CAG repeats, a series of three DNA building blocks. This results in the production of an abnormally long huntingtin protein that forms toxic clumps in nerve cells, ultimately causing a range of symptoms, including motor, cognitive, and behavioral issues, that progress over time.

Notably, CAG repeats can progressively lengthen over time, a process called somatic CAG repeat expansion, with longer repeats associated with earlier onset and more severe disease.

SKY-0515 is designed to reduce the production of mutant and healthy forms of the huntingtin protein, as well as PMS1, a DNA-repair protein involved in somatic CAG repeat expansion. This is expected to reduce the formation of toxic huntingtin clumps, and slow or halt Huntington’s progression.

Therapy snapshot

How will SKY-0515 be administered?

Several doses of SKY-0515, taken once daily, have been tested in Huntington’s clinical trials. A Phase 1 trial’s sub-study is testing 3 mg and 9 mg oral capsules of the therapy, while a Phase 2/3 trial is testing three doses (not disclosed to date).

SKY-0515 in clinical trials

The safety, tolerability, and pharmacological properties of single or repeated ascending doses of SKY-0515 were assessed against a placebo in healthy adults within a Phase 1 trial (ACTRN12623001161617). Results demonstrated that SKY-0515, tested at doses ranging from 1 mg to 16 mg, had a favorable safety and tolerability profile and reduced huntingtin levels by up to 72% in a dose-dependent manner.

A Phase 1 trial’s sub-study (ACTRN12624000602527) is testing SKY-0515 at two dose levels (3 and 9 mg) against a placebo in up to 50 adults with Huntington’s. The treatment is being administered once daily for about three months.

Subsequently, Skyhawk launched the Phase 2/3 FALCON-HD trial (NCT06873334) to assess SKY-0515’s safety, efficacy, and pharmacological properties in up to 120 adults, ages 25 and older, with stage 2 and early stage 3 Huntington’s, marked by impairments to daily activities and further symptom worsening. Participants are randomly assigned to receive either one of three SKY-0515 doses or a placebo for a year.

Two of FALCON-HD’s main goals are to assess changes in the blood levels of mutant huntingtin and PMS1, as well as in brain volume assessed by MRI. The other main goal includes changes in the Unified Huntington’s Disease Rating Scale, a validated tool to evaluate movement, cognitive skills, behavior, and functional independence in people with Huntington’s.

The first patient was dosed in June 2025 and the study is set to end in 2027.

SKY-0515 side effects

To date, Skyhawk has released no information regarding the treatment’s potential side effects in healthy volunteers or people with Huntington’s.

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