By medical correspondent
September 17, 2025
In the biotech hub of Cambridge, Massachusetts, the seasons are usually marked by the academic calendar of MIT and Harvard, or the quarterly earnings calls of the giants on Kendall Square. But for the families living in the shadow of Huntington’s Disease, time is measured differently. It is measured in a countdown they pray will stop. It is a perpetual winter, a season of waiting for a thaw that, for decades, has refused to come.
But this Wednesday, even though the leaves on the Charles River had only just begun to turn, it felt like Christmas Morning.
Skyhawk Therapeutics, a company that has been quietly working in its “workshop” on a new class of drugs, unwrapped a present that the medical community has been desperate to open. They released the first clinical trial data for their oral drug, SKY-0515. For a community accustomed to coal in their stockings—failed trials, toxic side effects, and broken promises—the data wasn’t just good. It was a miracle.
The Longest Winter
To understand the magnitude of Skyhawk’s announcement, one must understand the cold reality of Huntington’s Disease (HD). It is often described by neurologists as the cruelest disease known to man—a genetic blizzard that combines the physical deterioration of ALS, the memory loss of Alzheimer’s, and the mood instability of schizophrenia.
And unlike those diseases, which strike randomly, Huntington’s is a family curse. If a parent has it, the child has a 50-50 coin flip of inheriting the “stutter.”
The “stutter” is a genetic glitch. In the huntingtin (HTT) gene, three DNA letters—C-A-G—repeat themselves. In a healthy person, they repeat 10 to 35 times. In a person with Huntington’s, the record skips. It repeats 40, 50, or more times. This repetition creates a toxic, mutant protein (mHTT) that slowly clumps together in the brain, strangling neurons and dimming the lights of the mind.
For decades, scientists have tried to turn off this snow machine. They have tried gene therapies that require drilling into the skull. They have tried spinal injections that feel like medieval torture.
And time and again, the results have been heartbreaking. The “Ghost of Christmas Past” in the Huntington’s field is the 2021 failure of the Roche and Ionis Phase 3 trial. That drug, tominersen, was the great white hope. When the trial was halted due to lack of efficacy, a deep freeze settled over the patient community. It felt like the Grinch had not just stolen the presents, but burned down the tree.
Until this week.
Unwrapping the Data
Skyhawk Therapeutics took a different approach. Led by CEO Bill Haney—a man who, in interviews, exudes the pragmatic optimism of a master toymaker convinced he can fix a broken mechanism—the company decided not to use a sledgehammer, but a scalpel. And they decided to put it in a pill.
On Wednesday, the company released the data from their Phase 1 study. In the clinical trial world, Phase 1 is usually just about safety—checking to see if the reindeer can fly without crashing. But Skyhawk checked to see if they could deliver presents, too.
They tested two “stocking stuffers”—two different dose levels of SKY-0515—on patients over the course of 84 days.
The results were dazzling.
The 9 mg Dose: In the group of ten patients who received the higher dose, the levels of the toxic mutant protein in their blood plummeted by 62%. To put that in perspective, imagine a blizzard that has been raging for years suddenly stopping, the clouds parting, and the sun melting away two-thirds of the snow in just three months.
The 3 mg Dose: Even in the lower dose group, the toxic protein levels dropped by 29%.
The Placebo: In the six patients who received the sugar pill—the control group—the winter raged on. CEO Bill Haney noted there was “essentially no reduction” in their toxic protein levels.
“The mechanism by which we reduce the Huntington’s protein is to drive its decay,” Haney explained, sounding less like a corporate executive and more like a mechanic explaining how he fixed an engine. “It basically eliminates the ability to continue to build the mutant huntingtin protein up.”
The Magic of the Mechanism
What makes SKY-0515 the “shiny new toy” that everyone wants to play with? It comes down to how it works.
Most drugs try to mop up the water after the pipe has burst. Skyhawk is trying to turn off the faucet.
SKY-0515 is an RNA modulator. If DNA is the instruction manual for building a human, and proteins are the furniture, RNA is the worker reading the manual and building the chair. In Huntington’s patients, the manual has a typo (the triplet repeat), so the RNA builds a broken, dangerous chair.
Skyhawk’s drug acts like a spell-checker. It binds to the RNA and essentially tells the cell, “This instruction is bad. Throw it away.”
But here is the extra dash of holiday magic: SKY-0515 targets two specific things. It targets the huntingtin gene itself, but it also targets a gene called PMS1.
PMS1 is a “mismatch repair” gene. In Huntington’s, PMS1 can actually make things worse—it acts like a mischievous elf, amplifying the errors and making the DNA stutter even longer as the patient ages. By targeting both HTT and PMS1, Skyhawk hopes to not only lower the toxic protein but also stop the genetic mutation from getting worse over time.
It is a dual-threat approach, wrapped in a simple, swallowable pill.
A Gift of Convenience
We often forget, amidst the high science, the human toll of treatment.
Currently, the other main contenders in the race—like uniQure—are working on gene therapies. These are the Ferraris of medicine: powerful, but incredibly expensive and difficult to maintain. UniQure’s treatment involves brain surgery. It is invasive. It is terrifying for a family already dealing with neurological decline.
Other treatments, like the one being developed by PTC Therapeutics (PTC518), are also oral, but they have had a rocky sleigh ride. Their data in May disappointed investors, leaving a question mark hanging over the program like a burnt-out bulb on a string of lights.
Skyhawk’s SKY-0515 offers something precious: normalcy.
Imagine a mother with Huntington’s. She doesn’t have to go to a neurosurgery center. She doesn’t have to undergo a spinal tap. She wakes up on Christmas morning, has her coffee, watches her kids open their presents, and takes a pill. That’s it.
That freedom is a gift that cannot be quantified in a spreadsheet.
Haney believes this differentiation—cost and convenience—is key. But in the spirit of the season, he refused to throw snowballs at his competitors.
“Anything that helps patients, I think, is good,” Haney said, displaying a camaraderie rare in the cutthroat biotech industry. “So I hope our friends at uniQure get their therapy approved. I expect that regulators and patient advocacy groups will make the decision about what’s good for the well-being of the patient, which is certainly what I’m focused on.”
The Ghosts of Christmas Future
It is important to remain cautious. This is Phase 1 data. We are in the early days of Advent; we haven’t reached the Epiphany yet.
There are still hurdles. The drug needs to prove it actually slows the symptoms—the chorea (jerky movements), the cognitive fog, the mood swings—not just lowers the protein levels in the blood. Lowering the protein is a “biomarker,” a signpost that says we are going the right direction, but the destination is still miles away.
There is also the question of safety. So far, SKY-0515 looks well-tolerated, but larger trials are the true test.
However, for the families of the Huntington’s community, hope is a currency they have been bankrupt of for too long. Today, Skyhawk replenished their accounts.
In online forums and support groups—the digital town squares where these families gather—the mood has shifted. For years, the posts have been litanies of decline, tips on how to manage feeding tubes, and shared grief over loved ones lost.
This week, the posts are different. They are sharing links to the Skyhawk data. They are using exclamation points. They are using the word “when” instead of “if.”
One user, a young man from Ohio who tested positive for the gene last year, wrote: “I’ve been scared that by the time I’m 40, I won’t know my own name. Reading this today… it feels like I just got granted a stay of execution. It feels like maybe, just maybe, I’ll get to be a grandpa one day.”
The Morning Star
As September bleeds into October, and the New England chill begins to settle over Cambridge, the lights in the Skyhawk labs are burning late. They are planning the next steps, the larger trials, the path to the FDA.
But for a moment, let us pause and appreciate the view.
For decades, Huntington’s Disease has been a story of darkness. It has been a long, cold night with no moon. But science, at its best, is the lighting of a candle.
With a 62% reduction in toxic protein, Skyhawk hasn’t just lit a candle. They have launched a flare. They have signaled that the mechanism works. They have proven that this “undruggable” target can be hit, and it can be hit hard.
It may be September on the calendar, but for thousands of families across America and the world, the release of this data feels like the first bells of Christmas ringing out over a silent, snowy field. The wait is not over, but for the first time in a long time, the silence has been broken by a sound other than grief.
It is the sound of progress. It is the sound of a future being rewritten. It is the sound of a simple, oral pill that might just save Christmas for generations to come.
