PMS1

Skyhawk presents today on its novel SKY-0515 small molecule RNA splicing modulator targeting Huntington's Disease to members of the Huntington's Disease Youth Organization, at the annual HYDO International Congress in Prague, Czech Republic. BOSTON, March 15, 2025 /PRNewswire/ -- Skyhawk Therapeutics, Inc., a clinical-stage biotechnology company developing novel small molecule therapies designed to modulate critical RNA targets, today 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. Continue Reading SKY-0515 is Skyhawk's investigational small molecule RNA splicing modifier developed through the company's novel RNA-splicing platform. SKY-0515 is designed to reduce both HTT protein and PMS1 protein, an additional key driver of somatic CAG repeat expansion and HD pathology. Skyhawk Presents at Huntington's Disease Youth Organization International Congress 2025 Post this "We are excited to present on our Huntingtin-lowering clinical trials at the HDYO International Congress this month," said Sergey Paushkin, Chief Scientific Officer and Head of R&D at Skyhawk, "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." Huntington's disease is a rare hereditary neurodegenerative disease affecting over 40,000 patients in the United States and many more worldwide. There are no approved treatments that can reverse or slow its course of progression. "We are pleased with the speed at which we've conducted our studies thus far and are focused on this patient community in great need", said Bill Haney, Chief Executive Officer at Skyhawk. "SKY-0515's compelling results thus far demonstrate the immense potential of our platform to target indications for which there are no approved disease modifying therapies." About Skyhawk Therapeutics Skyhawk Therapeutics is a clinical-stage biotechnology company focused on the discovery and development of novel small molecule therapies designed to modulate critical RNA targets and revolutionize patient treatment for some of the world's most intractable diseases. Skyhawk's discovery expertise is rooted in its proprietary drug discovery platform, which assesses, identifies, and tests RNA splicing targets and small molecules across a broad range of therapeutic areas and disease states. Skyhawk has built collaborations with multiple pharma partners that leverage Skyhawk's novel platform across disease areas including neurodegenerative disease, autoimmune disease, and oncology. For more information visit . Skyhawk Contact Maura McCarthy [email protected] SOURCE Skyhawk Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Skyhawk’s SKY-0515 demonstrated dose-dependent huntingtin (HTT) mRNA reduction in healthy volunteers, with 72% reduction at the highest dose tested in the multiple ascending dose study SKY-0515 was generally well tolerated at all doses tested 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 July 10, 2024 -- 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. SKY-0515 is Skyhawk’s investigational small molecule RNA splicing modifier developed through the company's novel RNA-splicing platform. SKY-0515 is designed to reduce both HTT protein and PMS1 protein, an additional key driver of somatic CAG repeat expansion and HD pathology. “Huntingtin-lowering and somatic expansion have been two of the hottest targets in HD research in the past decade. Reducing both HTT and PMS1 could have greater therapeutic benefit than lowering HTT alone,” said Ed Wild, Professor of Neurology at University College London. “Huntington’s disease is a rare hereditary neurodegenerative disease affecting over 40,000 patients in the United States. There are no approved treatments that can reverse or slow its course of progression. SKY-0515’s HTT reduction has the highest dynamic range I’ve seen from any therapeutic modality and gives me great hope for SKY-0515’s potential to one day help those patients in need.” “We believe that, with these impressive HTT mRNA lowering results and the drug’s predicted suppression of the PMS1 protein, SKY-0515, if approved, could make a meaningful difference in Huntington’s patients’ lives,” said Douglas V. Faller, M.D., Ph.D., Chief Medical Officer, Skyhawk Therapeutics. “The Safety Review Committee has determined that SKY-0515 has been generally well tolerated at all tested doses with a dose proportional increase in systemic exposure and, given these favorable safety results, approved this study to move into the patient arm. Recruitment has begun, and topline data from this part of the trial are expected to report in Q2 2025.” “After initiating this Phase 1 clinical trial in late 2023, we’re delighted with the speed at which we’ve conducted this study and thrilled to report such compelling results for SKY-0515,” said Clint Musil, Chief Executive Officer, Skyhawk Therapeutics. “These topline data represent a crucial step forward for SKY-0515 and demonstrate the immense potential of the Skyhawk platform to target indications for which there are no approved disease modifying therapies.” HTT mRNA levels in the blood from pre-dose are described in the charts below. SAD: Maximum reduction in HTT mRNA level in blood from pre-dose within 24 hours after single dose MAD: Average reduction in HTT mRNA level in blood from pre-dose over 24 hours post dose on day 14 SKY-0515 is currently being evaluated in a Phase 1 clinical trial. The Phase 1 clinical trial is a first-in-human trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics, specifically blood biomarker modulation activity, of SKY-0515 in healthy volunteers and individuals with early-stage Huntington’s disease (HD). The trial is separated into three parts. Parts A and B evaluated SKY-0515 in healthy volunteers. Part A was a double-blind placebo-controlled single ascending dose study in healthy adult volunteers. In Part A, five cohorts of participants were dosed with escalating single doses of SKY-0515 ranging from 1mg to 16mg or placebo. Additionally, the influence of food on the pharmacokinetics of SKY-0515 was examined in a dedicated cohort. Part B was a double-blind placebo-controlled multiple ascending dose study in healthy adult volunteers. In Part B, three cohorts of participants were randomized to receive multiple ascending doses of SKY-0515 ranging from 1mg to 9mg or placebo administered daily from days 1 to 14 (inclusive). Dose levels of SKY-0515, identified in Parts A and B, will be evaluated in Part C. Part C is a double-blind placebo-controlled parallel design study of two dose levels of SKY-0515 and placebo of individuals with early-stage HD (HD-ISS Stage 1, 2, or mild Stage 3) preceded by an observational period lasting a minimum of 28 days, which aims to evaluate pharmacodynamic parameters such as mutant HTT protein and mRNA. Recruitment for Part C has begun, and topline data are expected in Q2 2025. Skyhawk Therapeutics is a clinical-stage biotechnology company focused on the discovery and development of novel small molecule therapies designed to modulate critical RNA targets and revolutionize patient treatment for some of the world’s most intractable diseases. Skyhawk’s discovery expertise is rooted in its proprietary drug discovery platform, which assesses, identifies, and tests RNA splicing targets and small molecules across a broad range of therapeutic areas and disease states. Skyhawk has built collaborations with multiple pharma partners that leverage Skyhawk’s novel platform across disease areas including neurodegenerative disease, autoimmune disease, and oncology. For more information visit www.skyhawktx.com. The content above comes from the network. if any infringement, please contact us to modify.

SKY-0515 is a small molecule RNA splicing modifier developed through the company's novel SKYSTAR® platform. Having successfully advanced through single asending dose, SKY-0515 is advancing into the Multiple Ascending Dose portion of its phase 1 study. Huntington's disease is a fatal neurological disease with no curative therapies. WALTHAM, Mass., Feb. 28, 2024 /PRNewswire/ -- Skyhawk Therapeutics, Inc., a clinical-stage biotechnology company developing novel small molecule RNA splicing modifiers, today 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). Huntington's is caused by a toxic 'CAG' repeat in the huntingtin (HTT) gene, causing mutated huntingtin protein. SKY-0515 is designed to modify the RNA expression of HTT, reducing the production of mutated protein that leads to disease progression in Huntington's patients. "We are excited to announce that after successfully advancing in our SKY-0515 Phase 1 single ascending dose study, the safety review committee has recommended initiation of the multiple asending dose portion of our Phase 1," said Douglas Faller, Chief Medical Officer of Skyhawk Therapeutics. "Following this, we expect to begin enrolling Huntington's patients, who presently have few therapeutic options and none that reverse or slow disease progression. SKY-0515 has demonstrated strong activity in our preclinical models which we believe will translate to patient benefit." There are approximately 30,000 symptomatic Huntington's disease patients in the US alone and many more who are pre-symptomatic. There are currently no approved drugs that reverse or slow disease progression for Huntington's patients. SKY-0515 is a small molecule which directly targets HTT RNA, is dosed orally and offers brain penetration and distribution in peripheral tissues which may provide important benefits to patients. It is the first Skyhawk-developed drug to enter clinical trials. 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, in Huntington's patients. Additional information about the trial can be found at: Australian New Zealand Clinical Trials Registry ( ). About SKY-0515 Skyhawk Therapeutics is developing a small molecule RNA splicing modifier for potential treatment of Huntington's disease through the company's novel SKYSTAR® platform. SKY-0515 is designed to reduce the production of the mutated huntingtin protein which results in disease progression. SKY-0515's predicted PK allows for daily, oral dosing, and the molecule is designed for brain penetration and distribution in peripheral tissue. About Huntington's disease Huntington's disease is an inherited disease that causes the progressive degeneration of nerve cells in the brain. Huntington's disease has a wide impact on a person's functional abilities and usually results in movement, cognitive and psychiatric disorders, and is ultimately lethal. Huntington's disease symptoms can develop at any time, but they often first appear when people are in their 30s or 40s. Medications are available to help manage the symptoms of Huntington's disease, but there is no cure for Huntington's disease, and currently no approved drugs that delay the disease onset or slow disease progression. About Skyhawk Skyhawk develops therapies using its novel SKYSTAR® platform, building small molecules that modify RNA expression to provide breakthrough treatments for patients. Skyhawk has productive collaborations across a broad range of disease areas, from neurodegenerative disease to oncology. For more information visit: SKYHAWK MEDIA CONTACT: Maura McCarthy maura@skyhawktx.com