Rugonersen's Phase 3 BEACON Trial Doses First Participant

Oak Hill Bio announced that the first participant has been dosed in BEACON (NCT07605429), a pivotal phase 3 trial evaluating rugonersen, an investigational antisense oligonucleotide (ASO), for Angelman syndrome. Angelman syndrome affects an estimated 15,000 individuals in each of the US and EU5 and currently has no approved disease-modifying treatment.¹

“The dosing of the first participant in the BEACON trial marks an important milestone for the rugonersen development program and for the Angelman syndrome community,” Brenda Vincenzi, MD, chief medical officer of Oak Hill Bio, said in a statement.¹ “Building on encouraging preclinical findings and the Phase 1 TANGELO trial, which demonstrated promising safety, target engagement, and signals of clinical activity, BEACON is designed to further evaluate the efficacy and safety of rugonersen.”

Trial design

BEACON is a global, randomized, double-blind, sham-controlled, multicenter trial designed to enroll up to 165 participants with Angelman syndrome aged 1 to 50 years. Participants are randomized 1:1 to receive either a sham procedure or 120 mg of rugonersen administered intrathecally once every 12 weeks.

The primary endpoint is improvement from baseline in cognition and/or expressive communication raw scores on the Bayley Scales of Infant and Toddler Development, Fourth Edition (BSID-4), measured after 56 weeks. Participants who complete the 56-week period are eligible for an open-label extension providing an additional 2 years of rugonersen treatment and long-term safety and efficacy follow-up. Oak Hill Bio expects to report topline BEACON results in early 2029.¹

Supporting phase 1 data

BEACON follows TANGELO, a Roche-led, open-label, multicenter, multiple ascending intra-patient dose-escalation phase 1 trial that enrolled 61 children with Angelman syndrome aged 1 to 12 years, with results published in Nature Medicine in 2025.² Rugonersen produced a dose-dependent reduction in EEG delta power, a pharmacodynamic biomarker of abnormal brain activity in Angelman syndrome, and exploratory assessments showed developmental gains exceeding natural-history expectations across 4 of 5 Bayley-III behavioral domains and all 5 Vineland Adaptive Behavior Scale domains tested.

Across more than 450 intrathecal administrations in the 61 participants, some treated for up to 4 years, the most common adverse events were transient pyrexia and vomiting. Serious adverse events occurred in 34% of participants, with 13% of participants (2% of administrations) experiencing events considered treatment-related, including seizure, epilepsy, vomiting, pyrexia, and post-lumbar puncture syndrome; no participants discontinued due to adverse events.

"These are promising results that mark a major milestone in the development of disease-modifying therapies for Angelman syndrome," Mark Shen, PhD, assistant professor of neuroscience and psychiatry at the University of North Carolina School of Medicine and a TANGELO investigator, said in a statement.² Wen-Hann Tan, MD, an Angelman syndrome specialist at Boston Children's Hospital and Harvard Medical School who was not involved in the study, added that the results "provide support for further investigation of rugonersen and UBE3A-targeting strategies in randomized controlled trials and highlight the potential value of EEG as a biomarker."²

Mechanism and background

Angelman syndrome results from loss of function of the maternally inherited UBE3A gene; in neurons, the paternal copy is normally silenced by a long non-coding antisense transcript, UBE3A-ATS.¹ Rugonersen is designed to bind and trigger degradation of UBE3A-ATS, unsilencing the paternal allele and restoring neuronal UBE3A expression.¹

Rugonersen (RO7248824) was originally developed by Roche, which led TANGELO before licensing global rights to Oak Hill Bio in April 2025.³ "Many of our trial participants have had meaningful improvements while in the rugonersen trial, and the TANGELO results suggest developmental and functional gains in multiple domains relative to natural history," Elizabeth Berry-Kravis, MD, PhD, a pediatric neurologist at Rush University Medical Center and TANGELO's principal investigator, said at the time of the licensing announcement.³

REFERENCES
1. Oak Hill Bio Announces Dosing of First Participant in BEACON Phase 3 Clinical Trial of Rugonersen in Angelman Syndrome. News release. Oak Hill Bio. July 28, 2026. Accessed August 12, 2026. https://www.oakhillbio.com/news/oak-hill-bio-announces-dosing-of-first-participant-in-beacon-phase-3-clinical-trial-of-rugonersen-in-angelman-syndrome
2. Hipp JF, Bacino CA, Bird LM, et al. The UBE3A-ATS antisense oligonucleotide rugonersen in children with Angelman syndrome: a Phase 1 trial. Nat Med. 2025. doi:10.1038/s41591-025-03784-7
3. Oak Hill Bio Enters into Exclusive License Agreement with Roche to Obtain Global Rights for a Phase 3-Ready, Potential Best-in-Class Treatment for Individuals with Angelman Syndrome. News release. Oak Hill Bio. April 15, 2025. Accessed August 12, 2026. https://www.oakhillbio.com/news/oak-hill-bio-enters-into-exclusive-license-agreement-with-roche-to-obtain-global-rights-for-a-phase-3-ready-potential-best-in-class-treatment-for-individuals-with-angelman-syndrome