Dive Brief:
- Skyhawk Therapeutics, a Boston-based biotechnology company, has unveiled final results from a small study testing a once-daily, “RNA splicing” pill as a treatment for Huntington’s disease.
- The findings, announced Tuesday, show that 15 months into treatment, Huntington’s patients taking Skyhawk’s pill improved by an average of 0.94 points on a complex scale used to assess their function, cognition and movement. That’s 1.59-points better than the study’s comparison group of untreated patients from a “natural history” database, who declined an average of 0.65 points over the same timeframe. Some neurology researchers have estimated that a 1.2-point change on this scale is “clinically meaningful.”
- Skyhawk said its drug has been generally well-tolerated, with no serious adverse events reported. And at a higher dose, it has consistently lowered mutant huntingtin protein — the main driver of disease — by more than 60%. The company is now evaluating the drug, codenamed SKY-0515, across two larger clinical trials, one of which has completed enrollment.
Dive Insight:
Skyhawk emerged from stealth mode in early 2018 with $8 million in seed funding from investors like Alexandria Venture Investments and Tim Disney of the Disney family. But it wasn’t long before more money came pouring in. By June of that year, the company had raised $40 million more and inked a $60 million strategic collaboration. Then, in 2021, it completed a $133 million oversubscribed round led by Fidelity Management & Research.
Skyhawk’s aim has been to find and develop small molecule drugs that “correct” RNA expression, namely by getting the cellular machinery that reads the instructions for making proteins to skip over defective sections. When it launched, Skyhawk noted how this “exon skipping” approach could be used to treat more than 50 diseases, including broad neurological conditions and thought-to-be "undruggable" oncogenes in cancer.
In Huntington’s, mutations lead to faulty huntingtin protein that then damages nerve cells. SKY-0515 is designed to inhibit not only the production of huntingtin, but also another protein, “PMS1,” that repairs DNA and can exacerbate the root problem of the disease. A higher dose of the drug dependably cut levels of PMS1 messenger RNA by 25% throughout the study, according to Skyhawk.
The company said, too, that at every key checkpoint in its study — three months, six months, nine months, 12 months and 15 months — patients on SKY-0515 were doing better than the comparison group. Those differences became statistically significant from the nine-month mark onward.
A late-stage program named “FALCON” is underway. There, one trial has recruited 144 participants with Stage 2 and Stage 3 Huntington’s disease in sites across Australia and New Zealand. A separate, worldwide study is still adding participants, hoping to reach a total enrollment of around 600.
