Skyhawk Therapeutics announces twelve-month results from Phase 1/2 clinical trial of SKY-0515 in Huntington’s disease.
Twelve-month findings showed improvement in Composite Unified Huntington’s Disease Rating Scale (cUHDRS) which is a method of scoring used to evaluate disease progression in early-to-moderate manifest Huntington’s disease. The scores were from baseline of +0.38, compared to an expected decline of -0.92 points over 12 months based on a natural history analysis of symptomatic patients.
SKY-0515 patients achieved reductions of 69% mutant huntingtin protein (mHTT) at the 9 mg dose at twelve months.
What does this mean?
Treatment with SKY-0515 resulted in dose-dependent reductions in mutant huntingtin (mHTT) protein in blood of up to 69% as well as reductions in PMS1 mRNA of up to 26%. Mutant huntingtin is the primary protein responsible for Huntington's pathology, while PMS1 is a key driver of somatic CAG repeat expansion associated with disease progression. SKY-0515 has demonstrated excellent central nervous system exposure and has been generally safe and well-tolerated across dose levels studied.
At three, six, nine and twelve months, patients receiving SKY-0515 demonstrated positive mean changes from baseline Composite Unified Huntington's Disease Rating Scale (cUHDRS) scores ranging from +0.31 to +0.38. These findings compared favorably with an expected worsening of -0.92 points over twelve months from propensity score-weighted analyses which use Enroll-HD and TRACK-HD natural history datasets. Favorable trends for patients on SKY-0515 were also observed across all cUHDRS subcomponents, including Total Motor Score (TMS), Total Functional Capacity (TFC), Symbol Digit Modalities Test (SDMT), and Stroop Word Reading Test (SWRT).
Phillip Sharp, PhD, Founding Member of Skyhawk’s Scientific Advisory Board and Nobel Prize Laureate for his groundbreaking work on RNA splicing said:
Skyhawk’s results show the extraordinary power of the ability to modulate RNA splicing with a small molecule, offering a therapy to patients worldwide. The RNA revolution continues and I couldn’t be more delighted to see what Skyhawk is doing to advance it.
Bill Haney, Co-founder and Chief Executive Officer of Skyhawk Therapeutics said:
The increasing separation of the clinical trajectories of treated participants from natural history expectations at the twelve-month timepoint suggests exciting and sustained benefits for Huntington’s patients. The magnitude and durability of lowering of critical biomarkers mHTT and PMS1, as well as encouraging twelve-month clinical findings across all four of the critical cUHDRS subcomponents, reinforce our confidence in SKY-0515’s differentiated mechanism and potential for dramatic therapeutic impact for patients.
Ed Wild, Professor of Neurology at University College London said:
I am very encouraged by these continued safety and efficacy data from SKY-0515’s Phase 1/2 trial in patients, including sustained improvement in patients’ cUHDRS when compared with expected propensity-weighted natural history deterioration at each of three, six, nine and twelve-month prespecified analyses. SKY-0515 continues to reduce mHTT protein to the greatest extent demonstrated in patients, with clinical and biomarker data showing the drug is well tolerated at all doses tested. SKY-0515’s ability to reduce both mHTT and PMS1 appears to be a potent combination for treating Huntington’s disease via two of its core pathogenic mechanisms. These Phase 1/2 trial results, due to be validated in the ongoing Phase 2/3 FALCON-HD pivotal program, give an expectation of meaningful therapeutic impact for people living with Huntington's across the world – for whom an orally administered huntingtin-lowering treatment such as SKY-0515 will be truly transformative.
There are currently no approved therapies shown to slow or halt Huntington's disease progression. The results announced today from the ongoing Phase 1/2 trial of SKY-0515, now including data from patients who were previously on placebo. It highlights the power of Skyhawk’s SKYSTAR® platform to generate potentially transformative medicines which patients can take as a daily pill at home, for people affected by neurological and other disabling diseases.
FALCON-HD
The Company also announces that the Australia and New Zealand (004-ANZ) portion of its Phase 2/3 FALCON-HD pivotal study completed enrollment six months ahead of schedule with 144 patients enrolled, and that the worldwide (004-WW) Phase 2/3 FALCON-Huntington's pivotal study has expanded to eight countries.
More than 175 patients are now enrolled across the SKY-0515 Phase 1/2 and FALCON-HD pivotal studies. Skyhawk expects to advance additional new therapies targeting rare neurological diseases with no approved disease-modifying treatment into clinical development by the end of 2027.
Bill Haney, Co-founder and Chief Executive Officer of Skyhawk Therapeutics said:
With enrollment in the FALCON-HD ANZ pivotal study completed ahead of schedule, we are rapidly advancing toward the next stage of development for SKY-0515 and remain committed to doing all we can to deliver a potentially transformative oral therapy to the Huntington’s disease community at the earliest possible time.
About Skyhawks Therapeutics
Skyhawk Therapeutics is a clinical-stage biotechnology company developing novel small-molecule therapies designed to modulate RNA targets.
About SKY-0515
SKY-0515 is an orally administered investigational small molecule RNA splicing modifier developed using the company's proprietary SKYSTAR® platform. SKY-0515 is designed to reduce both mHTT and PMS1 proteins.