Skyhawk's Lead Programs
Positive Topline Results from its Phase 1 Clinical Trial of SKY-0515 as a Treatment for Huntington’s Disease
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Skyhawk’s SKY-0515 was well tolerated at all doses tested, with no treatment-related severe-adverse events (SAEs).
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SKY-0515 demonstrated dose-dependent huntingtin (HTT) mRNA reduction of 72% at the highest dose tested.
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Given these favorable results, this study will now move into the patient arm which is expected to report topline data in 2Q 2025.
Skyhawk Therapeutics, Inc., a clinical-stage biotechnology company developing novel small molecules designed to modulate critical RNA targets, today announced positive results from its Phase 1 clinical trial of SKY-0515, which is being evaluated as a potential treatment for Huntington’s disease (HD). SKY-0515 demonstrated an average mHTT reduction of 72% at a dose of 9mg with no significant safety or tolerability issues.
SKY-0515 is Skyhawk’s small molecule RNA splicing modifier developed through the company's novel RNA-splicing platform. SKY-0515 reduces both mutant Huntington protein and PMS1, an additional key driver of somatic CAG expansion and HD pathology. HD is a rare hereditary neurodegenerative disease that effects over 40,000 patients in the United States. HD is fatal and there are no approved treatments that can reverse or slow its course of progression.
“These positive, first in human data mark an important milestone for Skyhawk as they demonstrate SKY-0515’s ability to safely and significantly reduce mutant HTT protein,” said
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Douglas V. Faller, M.D., Ph.D., Chief Medical Officer of Skyhawk Therapeutics. “The Safety Review Committee showed SKY-0515 was generally well tolerated at all tested doses with a dose proportional increase in systemic exposure. Additionally, the results showed linear pharmacokinetics and the pharmacodynamic response provides dosing flexibility to reach significant HTT reduction. We believe that, with these HTT lowering results and its PMS1 activity, SKY-0515 has potential to make a meaningful difference in Huntington’s patient’s lives. Given these favorable results, this study will now move into the patient arm which is expected to report topline data in 2Q 2025.”
HTT mRNA levels in the blood from pre-dose are described in the charts below.
SAD: Maximum Reduction in HTT mRNA level in blood from pre-dose within 24 hours after single dose
MAD: Average HTT mRNA level in blood from pre-dose over 24 hours post dose on day 14
About SKY-0515 Phase 1 Clinical Study
SKY-0515 is currently being evaluated in a Phase 1 clinical trial. The Phase 1 clinical trial is a first-in-human trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics, specifically blood biomarker modulation activity, of SKY-0515 in healthy volunteers and early-stage HD patients. The trial is separated into three parts. Parts A and B evaluated SKY-0515 in healthy volunteers.
Part A was a double-blind placebo-controlled Phase 1 SAD clinical trial in healthy adult volunteers. In Part A, five cohorts were dosed with escalating single doses of SKY-0515 ranging from 1mg to 16mg or placebo. Additionally, the influence of food on the pharmacokinetics of SKY-0515 was examined in a dedicated cohort.
Part B was a double-blind placebo-controlled MAD in healthy adult volunteers, with three cohorts and a maximum of eight patients per cohort. Participants were randomized to receive multiple ascending doses of SKY-0515 ranging from 1 mg to 9 mg or placebo administered daily from Days 1 to 14 (inclusive). Dose levels of SKY-0515, identified in Parts A and B, will be evaluated in Part C.
Part C is a double-blind placebo-controlled parallel design study with two cohorts in early-stage HD patients (HD-ISS Stage 1, 2, or mild Stage 3) preceded by an observational period lasting a minimum of 28 days, which aims to establish a stable baseline of pharmacodynamic parameters such as HTT protein and mRNA. Recruiting for Part C has begun, and topline data are expected by Q2 2025.