Skyhawk's SKY-0515 Shows Promise in Huntington's Disease with 72% HTT mRNA Reduction
Key Insights
Skyhawk Therapeutics (search)' SKY-0515 demonstrated a 72% average reduction in huntingtin (HTT (search)) mRNA at a 9mg daily oral dose in healthy volunteers.
The Phase 1 clinical trial of SKY-0515 showed the drug was generally well tolerated across all tested doses in Parts A and B.
Part C of the Phase 1 trial, now enrolling patients with early-stage Huntington's disease (search), anticipates topline data in Q2 2025.
Skyhawk Therapeutics (search) announced additional positive topline data from Parts A and B of its Phase 1 clinical trial of SKY-0515, a novel small molecule being developed for Huntington's disease (search) (HD). The data, presented at the European Huntington's Disease Network and Enroll-HD 2024 meeting, highlighted SKY-0515's ability to reduce huntingtin (HTT (search)) mRNA levels significantly.
SKY-0515 achieved an average HTT (search) mRNA reduction of 72% at a daily oral dose of 9mg in healthy volunteers. The drug was generally well tolerated at all doses tested in Parts A and B of the Phase 1 trial. These results have paved the way for Part C of the trial, which is now enrolling patients with early-stage Huntington's disease (search), with topline data expected in Q2 2025.
SKY-0515 Phase 1 Trial Details
The Phase 1 trial is designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SKY-0515. Parts A and B of the trial were conducted in healthy volunteers. Part A was a double-blind, placebo-controlled, single ascending dose study, with participants receiving single doses of SKY-0515 ranging from 1mg to 16mg or placebo. Part B was a double-blind, placebo-controlled, multiple ascending dose study, where participants received daily doses of SKY-0515 ranging from 1mg to 9mg or placebo for 14 days.
Part C is a double-blind, placebo-controlled, parallel design study involving individuals with early-stage HD (HD-ISS Stage 1, 2, or mild Stage 3). This part of the trial aims to evaluate pharmacodynamic parameters, such as mutant HTT (search) protein and mRNA levels. Recruitment for Part C is underway.
Huntington's Disease and SKY-0515's Potential
Huntington's disease (search) is a rare, hereditary neurodegenerative disorder with no approved disease-modifying therapies. SKY-0515 is designed to reduce both HTT (search) and PMS1 (search) proteins, two key drivers of the disease. "Lowering HTT and stabilizing somatic expansion via PMS1 are two important therapeutic approaches being pursued in HD research," said Clint Musil, CEO at Skyhawk. "We believe [the data] underscore the potential of SKY-0515 to achieve both these important clinical objectives."