Skyhawk Shares A Closer Look at SKY-0515 Data, Plus A Peek At Expanding US Trial Access

On June 30th, Skyhawk Therapeutics shared a press release with new twelve-month data from the ongoing Phase 1/2 trial of SKY-0515, their HTT-lowering pill designed to treat Huntington’s disease (HD). This builds on the topline cUHDRS results the company shared just a few weeks ago, on June 1st, which showed sustained HTT lowering (up to 69%) and PMS1 reduction (up to 26%) in blood, alongside encouraging trends on the composite UHDRS (cUHDRS) scale. However, it’s still unclear whether PMS1 changes are sufficient to cause clinical benefit. Today’s release breaks the cUHDRS score down into its four individual components, all of which look promising, although there are some important caveats to consider. Skyhawk also shared new participant and clinician survey data, and a forward-looking update from the recent HDSA Convention highlights plans for trial expansion in the United States.

What the individual components show

The cUHDRS is a composite score built from four separate measures: 

• Total Functional Capacity (TFC) – tracks a person’s ability to manage daily life independently
• Total Motor Score (TMS) – a clinician-rated assessment of motor symptoms
• Symbol Digit Modalities Test (SDMT) – a measure of mental speed and attention 
• Stroop Word Reading Test (SWRT) – a measure of cognitive function

At twelve months, all four components were at or above baseline for participants on SKY-0515, and all four outperformed the expected trajectory from a propensity-score-weighted natural history comparison group (drawn from the Enroll-HD dataset). In other words, participants remained stable across all four measures, rather than seeing the gradual decline typically expected in HD.

The specifics of the data Skyhawk shared are that TFC showed a modest +0.07 change from baseline versus an expected decline of -0.87, TMS improved by -2.00 versus an expected worsening of +2.21, SDMT held essentially flat at -0.19 versus an expected -1.78, and SWRT improved by +3.44 versus an expected -3.13.

What stands out from this data

No single component appears to be driving the trend here. All four subscales are showing a favorable (if modest) improvement in scores relative to natural history. That’s worth noting because it’s a different shape of result than we’ve seen elsewhere in the field. In PTC/Novartis’s data, for example, people taking votoplam seemed specifically to do better on thinking tests; in this study, people taking SKY-0515 seemed to do better on all of the tests.

That’s a novel observation worth highlighting, but the studies are too different in length, size, and the way the data is presented to make a true comparison.  

It’s also worth flagging that Skyhawk presents “pooled” data from two angles: they combine all the data from people in HD-ISS Stage 1-3, and they combine data from the participants taking low (4 mg) and high (9 mg) doses of SKY-0515. This means we can’t yet see whether the drug could have different effects at different stages of HD, or if a higher dose has a stronger effect. Larger, longer studies like FALCON-HD are better positioned to answer these questions.

What participants and clinicians are reporting

Skyhawk also shared results from Clinician and Patient Global Impression of Change surveys collected over the twelve-month period. These surveys ask clinicians and participants to rate whether their overall condition has improved, stayed the same, or worsened over time. Among participants whose HD symptoms would typically be expected to worsen over a year, no clinicians or participants reported any disease worsening at the twelve-month mark. Instead, 65% of participants and 50% of clinicians reported that they’d seen improvement.

Let’s talk about what this kind of data can and can’t tell us. 

Global impression surveys are valuable because they capture how people are actually experiencing the treatment day-to-day, which is something a test score alone doesn’t always reflect. But they’re inherently subjective, shaped by expectation and perception, and they are not as influential towards showing that a drug is helpful as objective clinical measures like the cUHDRS itself. 

So while it’s encouraging that nobody in this group reported feeling like they were experiencing symptomatic decline, this survey data is best read as a complementary, supportive signal alongside numerical scales designed to track HD.

Context and caveats

This data comes from Part C of SKY-0515’s Phase 1/2 trial in people with early stage HD. The study began by randomly assigning participants to receive either SKY-0515 or a placebo before everyone received SKY-0515 for the rest of the twelve-month study. As Skyhawk notes, this is early data from an ongoing trial that has been shared by press release, and the findings could change as more participants continue in the trial and longer follow-up data become available.

What’s next

Skyhawk’s pivotal Phase 2/3 program, FALCON-HD, is already underway, having completed enrollment of 144 participants in Australia and New Zealand. A second arm, FALCON-HD 004-WW, is actively expanding worldwide, with plans to enroll up to 400 additional participants with Stage 2 and early Stage 3 HD across more than 40 sites globally.

For US families following this trial closely, there’s reason to pay attention in the coming weeks: at the recent HDSA Convention, Skyhawk shared that study sites are expanding to the US, with a Colorado site expected to begin recruiting as early as July 2026, additional sites planned to open in September and October, and a goal of five active US recruiting sites by the end of the year. We expect more concrete details, including specific locations and enrollment contacts, to be announced soon, so stay tuned!

In the meantime, full eligibility criteria for FALCON-HD are available at ClinicalTrials.gov, and additional trial information can be found at FALCON-HD.com.

Summary

• On June 30th, Skyhawk Therapeutics released new 12-month data from the Phase 1/2 trial of SKY-0515, breaking out the four individual components of the cUHDRS scale and sharing new participant/clinician survey results
• All four cUHDRS components (TFC, TMS, SDMT, and SWRT) were at or above baseline at 12 months and outperformed a natural history comparison group
• Unlike some other HTT-lowering candidates in development, no single subscale appears to be driving the SKY-0515 trend; all four are moving favorably together
• Clinician and Patient Global Impression surveys showed no reported disease worsening at 12 months, with 65% of participants and 50% of clinicians reporting improvement, though this kind of subjective data should be read as a complementary signal, not standalone proof of efficacy
• This is interim, unaudited data from an ongoing trial and is subject to change
• Skyhawk’s pivotal FALCON-HD program is actively expanding, with US site access on the horizon as July 2026, with more sites planned through the rest of the year
• Eligibility criteria for FALCON-HD are available at ClinicalTrials.gov, with additional info at FALCON-HD.com