SKY-0515 / Skyhawk Therap - LARVOL DELTA

Huntington's disease clinical trials update: October 2025. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the launch of the phase II/III clinical trial of SKY-0515 from Skyhawk Therapeutics and the phase I/II clinical trial of SPK-10001 from Spark Therapeutics. Further updates include recent developments in Roche's tominersen programme within GENERATION HD2, progress with votoplam (PTC518) in PIVOT-HD by PTC Therapeutics and developments in the collaborative PTC Therapeutics/Novartis programme. We also report positive topline data from uniQure's phase I/II clinical trial of AMT-130 after 36 months of follow-up. We additionally discuss regulatory developments regarding pridopidine following the negative PROOF-HD study. Finally, we provide an updated listing of all registered and ongoing clinical trials in Huntington's disease."

Journal • Huntington's Disease • Movement Disorders

Skyhawk Therapeutics, Inc…announced positive results from the first interim analysis of the Part C patient cohort in its Phase 1 clinical trial of SKY-0515, an investigational treatment for Huntington's disease (HD). (PRNewswire) - "SKY-0515 achieves dose-dependent reductions of mutant huntingtin (mHTT) protein, with 62% lowering at Day 84 on the 9mg daily oral dose; Additional findings include dose-dependent reductions in PMS1 mRNA, excellent brain penetration, and a favorable safety profile....Part C enrollment is complete, and topline data from the blinded active treatment extension are expected in mid-2026."

P1 data • Huntington's Disease

A Phase I Randomised, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effect of Food on the Bioavailability of SKY-0515 in Healthy Volunteers and Patients with Huntington’s Disease (ANZCTR) - P1 | N=50 | Completed | Sponsor: Skyhawk Therapeutics, Inc | Recruiting ➔ Completed

Trial completion • Huntington's Disease • Movement Disorders

Study of SKY-0515 for Safety, Efficacy, and Pharmacodynamics in Participants With Huntington's Disease (clinicaltrials.gov) - P2/3 | N=120 | Recruiting | Sponsor: Skyhawk Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Huntington's Disease • Movement Disorders

An Open-Label, Crossover, Relative Bioavailability Study Comparing Tablet and Capsule Formulations of SKY-0515 in Healthy Volunteers (ANZCTR) - P1 | N=16 | Completed | Sponsor: Skyhawk Therapeutics, Inc. | Not yet recruiting ➔ Completed

Trial completion • Huntington's Disease • Movement Disorders

Skyhawk Therapeutics Announces First Patient Dosed in Phase 2/3 FALCON-HD Trial of SKY-0515 for Huntington's Disease (PRNewswire) - "Skyhawk Therapeutics, Inc...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)....The trial includes multiple sites across Australia and New Zealand. The initial dosing took place at Flinders Medical Centre in Adelaide, Australia."

Trial status • Huntington's Disease

Skyhawk Therapeutics Presents at Huntington's Disease Youth Organization HDYO International Congress 2025 (Canada Newswire) - P=NA | N=NA | "Skyhawk Therapeutics...presents on its novel SKY-0515 small molecule RNA splicing modulator targeting Huntington's Disease to members of the Huntington's Disease Youth Organization (HDYO), at the biannual HYDO International Congress in Prague, Czech Republic...'We are excited to present on our Huntingtin-lowering clinical trials at the HDYO International Congress this month'....'with positive results including SKY-0515's average HTT mRNA reduction of 72% at a daily oral dose of 9mg in trials thus far, and the drug's predicted suppression of the PMS1 protein, SKY-0515, if approved, could make a meaningful difference in Huntington's patients' lives.'"

Clinical data • Huntington's Disease

Study of SKY-0515 for Safety, Efficacy, and Pharmacodynamics in Participants with Huntington's Disease (clinicaltrials.gov) - P2/3 | N=120 | Not yet recruiting | Sponsor: Skyhawk Therapeutics, Inc.

New P2/3 trial • Genetic Disorders • Huntington's Disease • Movement Disorders

An Open-Label, Crossover, Relative Bioavailability Study Comparing Tablet and Capsule Formulations of SKY-0515 in Healthy Volunteers (ANZCTR) - P1 | N=16 | Not yet recruiting | Sponsor: Skyhawk Therapeutics, Inc.

New P1 trial • Huntington's Disease • Movement Disorders

Skyhawk Therapeutics Receives Australian Regulatory Approval to Extend SKY-0515 Treatment Duration in Phase 1 Huntington's Disease Patient Trial (PRNewswire) - P1 | N=50 | ACTRN12624000602527 | "Skyhawk Therapeutics, Inc...today announced that the Australian Human Research Ethics Committees (HREC) have approved SKY-0515 treatment for up to 12 weeks in the Company's ongoing Phase 1 trial in patients with Huntington's Disease (HD). HREC also agreed to the inclusion of Volumetric MRI (vMRI) measurements as an early exploratory endpoint in the trial. vMRI measurement of the brain's regions affected in HD can provide additional data on SKY-0515's effect in HD patients....Topline pharmacodynamic results for Parts A (single-ascending dose) and B (multiple-ascending dose), which evaluated SKY-0515 in healthy volunteers, demonstrated a dose-dependent reduction of HTT mRNA and reached an average reduction of 72% at a daily oral dose of 9mg. SKY-0515 was generally well tolerated at all doses tested."

P1 data • Regulatory • CNS Disorders • Genetic Disorders • Huntington's Disease

A Phase I Randomised, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effect of Food on the Bioavailability of SKY-0515 in Healthy Volunteers and Patients with Huntington’s Disease (ANZCTR) - P1 | N=50 | Recruiting | Sponsor: Skyhawk Therapeutics, Inc | N=74 ➔ 50

Enrollment change • Huntington's Disease • Movement Disorders

Skyhawk Therapeutics to Present Additional Positive Topline Data from Parts A and B of Phase 1 Clinical Trial of SKY-0515 at European Huntington's Disease Network and Enroll-HD 2024 (PRNewswire) - "The presentation highlights additional positive topline results from SAD/MAD study and preclinical data of SKY-0515, a novel small molecule designed to reduce both HTT and PMS1 proteins, two key drivers of Huntington's disease....Part C of the Company's Phase 1 trial is now enrolling patients with Huntington's, and topline data are expected in Q2 2025."

P1 data • Preclinical • Trial status • CNS Disorders • Huntington's Disease

A Phase I Randomised, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effect of Food on the Bioavailability of SKY-0515 in Healthy Volunteers and Patients with Huntington’s Disease (ANZCTR) - P1 | N=74 | Recruiting | Sponsor: Skyhawk Therapeutics, Inc | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2024

Enrollment open • Trial initiation date • Huntington's Disease • Movement Disorders

Skyhawk Therapeutics Announces Positive Topline Results from Parts A and B of its Phase 1 Clinical Trial of SKY-0515 as a Treatment for Huntington’s Disease, Reaching 72% Huntingtin mRNA Reduction (GlobeNewswire) - P1 | N=168 | ACTRN12623001161617 | Sponsor: Skyhawk Therapeutics, Inc. | "Given these positive topline results, we anticipate dosing in the patient arm of the study in Q3 2024 and initiation of a Phase 2 study early next year....Skyhawk Therapeutics, Inc., a clinical-stage biotechnology company developing novel small molecule therapies designed to modulate critical RNA targets, today announced positive results from Parts A and B of its Phase 1 clinical trial of SKY-0515, which is being developed as a potential treatment for Huntington’s disease (HD). SKY-0515 demonstrated an average HTT mRNA reduction of 72% at a daily oral dose of 9mg and was generally well tolerated at all doses tested."

P1 data • CNS Disorders • Huntington's Disease

A Phase I Randomised, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effect of Food on the Bioavailability of SKY-0515 in Healthy Volunteers and Patients with Huntington’s Disease (ANZCTR) - P1 | N=74 | Not yet recruiting | Sponsor: Skyhawk Therapeutics, Inc

New P1 trial • Huntington's Disease • Movement Disorders

A Phase I Randomised, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamicsnand Effect of Food on the Bioavailability of SKY-0515 in Healthy Volunteers (ANZCTR) - P1 | N=168 | Recruiting | Sponsor: Skyhawk Therapeutics, Inc. | N=80 ➔ 168 | Initiation date: Nov 2023

Enrollment change • Trial initiation date • Huntington's Disease • Movement Disorders

Skyhawk Therapeutics Has Advanced to the Multiple Ascending Dose Portion of its Phase 1 Study evaluating SKY-0515, a RNA-Targeting Small Molecule for Huntington's Disease (Canada Newswire) - "Skyhawk Therapeutics, Inc...announced that the Phase 1 multiple ascending dose (MAD) portion of its Phase 1 clinical study has now begun in Australia for the company's SKY-0515 small molecule candidate targeting Huntington's disease (HD)."

Trial status • CNS Disorders • Huntington's Disease

A Phase I Randomised, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamicsnand Effect of Food on the Bioavailability of SKY-0515 in Healthy Volunteers (ANZCTR) - P1 | N=80 | Recruiting | Sponsor: Skyhawk Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Huntington's Disease • Movement Disorders

A Phase I Randomised, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamicsnand Effect of Food on the Bioavailability of SKY-0515 in Healthy Volunteers (ANZCTR) - P1 | N=80 | Not yet recruiting | Sponsor: Skyhawk Therapeutics, Inc.

New P1 trial • Huntington's Disease • Movement Disorders

Skyhawk Therapeutics Receives HREC Approval for a Phase 1 Study of its SKY-0515 RNA-Targeting Small Molecule for Huntington’s Disease (BioSpace) - "Skyhawk Therapeutics, Inc...today announced the Australian Human Research Ethic Committee (HREC) approval by Australian regulators for a clinical trial for Skyhawk's SKY-0515 small molecule candidate targeting Huntington's disease (HD)....Skyhawk Therapeutics' SKY-0515 Phase 1 clinical trial is a first-in-human, multi-part, randomized, double-blind, single and multiple ascending dose study designed to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of SKY-0515 monotherapy in healthy volunteers and, subsequently, Huntington's patients."

New P1 trial • CNS Disorders • Huntington's Disease