CAMBRIDGE, Mass. — Oak Hill Bio, a clinical-stage rare disease therapeutics company, today announced that the first participant has been dosed in BEACON, a pivotal Phase 3 clinical trial evaluating rugonersen, an investigational ASO for the treatment of Angelman syndrome.
“The dosing of the first participant in the BEACON (NCT07605429) trial marks an important milestone for the rugonersen development program and for the Angelman syndrome community,” said Dr. Brenda Vincenzi, Chief Medical Officer of Oak Hill Bio. “It is a privilege to once again work closely with individuals living with Angelman syndrome, their families, clinicians, and patient advocacy organizations as we advance this pivotal Phase 3 trial. 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. We are hopeful that this trial will bring us one step closer to delivering a meaningful treatment option for people living with Angelman syndrome, who continue to face significant unmet medical needs.”
Angelman syndrome is a neurodevelopmental disorder affecting approximately 15,000 individuals in each of the US and the EU5, caused by disruptions in the UBE3A gene leading to cellular damage within neurons. Rugonersen was originally developed by Roche to address the underlying disease biology of Angelman syndrome by restoring UBE3A expression.
Rugonersen’s previous Phase 1 TANGELO trial was conducted by Roche in pediatric Angelman syndrome participants aged 1-12 years and showed that treatment with rugonersen led to a dose-dependent partial normalization of pathological brain activity on a pharmacodynamic biomarker of brain function, electroencephalogram (EEG) delta power. Participants also exhibited improvements as compared to expectations based on natural history on multiple exploratory endpoints measuring the core symptoms of Angelman syndrome. Rugonersen showed a generally appropriate safety and tolerability profile in TANGELO. The data from TANGELO are extensively covered in Hipp et al, The UBE3A-ATS antisense oligonucleotide rugonersen in children with Angelman syndrome: a Phase 1 trial. Nature Medicine (2025).
The Phase 3 BEACON trial (NCT07605429) has been designed as a global, randomized, double-blind, sham-controlled, multi-center trial that will enroll up to 165 participants with Angelman syndrome aged 1-50 years. Participants will be randomized on a 1:1 basis to receive either sham procedure or 120 mg rugonersen by intrathecal injection once every 12 weeks. The primary endpoint, defined as improvement from baseline in Bayley Scale of Infant and Toddler Development, Fourth Edition (BSID-4) raw score in cognition and/or expressive communication, will be measured after 56 weeks. All participants completing 56 weeks will be eligible to participate in an open-label extension, which will administer rugonersen for an additional 2 years and allow for a long-term evaluation of rugonersen’s safety and efficacy. Oak Hill Bio expects to report topline results in early 2029.
About the BEACON Trial (NCT07605429)
BEACON is a pivotal Phase 3 randomized, double-blind, sham-controlled, multi-center trial designed to evaluate the efficacy and safety of intrathecally (IT) administered rugonersen compared with a sham procedure in up to 165 participants with Angelman syndrome aged 1-50 years.
About Rugonersen
Rugonersen is an antisense oligonucleotide (ASO) designed to address the underlying disease biology of Angelman syndrome (AS) by specifically and potently binding the UBE3A-ATS transcript. Rugonersen binding is intended to trigger degradation of the UBE3A-ATS transcript in the CNS and therefore the unsilencing of the UBE3A paternal allele. Rugonersen allows neuronal expression of the paternal wild-type copy of the UBE3A gene, potentially improving neuronal function and development in AS patients.
Rugonersen’s clinical and preclinical data are detailed in the following publications: Hipp, J.F., Bacino, C.A., Bird, L.M. et al. The UBE3A-ATS antisense oligonucleotide rugonersen in children with Angelman syndrome: a Phase 1 trial. Nat Med (2025). https://doi.org/10.1038/s41591-025-03784-7;
Jagasia et al., Angelman syndrome patient-derived neuron screen leads to clinical ASO rugonersen targeting UBE3A-ATS with long-lasting effect in monkeys, Nucleic Acids Research (2025). https://doi.org/10.1093/nar/gkaf851
About Angelman Syndrome
Angelman syndrome (AS) is a serious rare genetic neurodevelopmental disorder which causes severe mental and physical impairment and affects approximately 15,000 individuals in each of the US and the EU5, with an estimated incidence of 1 in 12,000 to 20,000 live births. AS is characterized by global developmental delay, intellectual disability, epilepsy (90% of cases before age 3 years) with an atypical underlying electroencephalogram (EEG), ataxia, tremor, hyperactivity, limited speech, and sleep dysregulation. Symptoms often emerge during infancy and persist throughout life. Deletions and mutations in the maternal ubiquitin protein ligase E3A (UBE3A) allele cause Angelman syndrome, due to epigenetic silencing of the paternal UBE3A allele by a long non-coding antisense RNA (UBE3A-ATS) in neurons. UBE3A is required for normal brain development and function. Failure to express UBE3A in central nervous system (CNS) neurons leads to a build-up of damaged or unwanted proteins, that if left unchecked, can paralyze normal neuronal maturation, function, and synaptic pruning.
About Oak Hill Bio
Oak Hill Bio is a clinical-stage biotechnology company focused on acquiring and developing promising therapeutics for rare diseases with significant unmet needs that have been deprioritized by pharmaceutical companies. The company’s lead program is rugonersen (OHB-724), an investigational antisense oligonucleotide (ASO) in Phase 3 clinical development as a potential best-in-class treatment for Angelman syndrome, a devastating neurodevelopmental disorder with no approved disease-modifying therapies.
Oak Hill Bio is the trading name for OHB Pediatrics Ltd. It was formed in 2024 as a subsidiary of Oak Hill Bio Holdings (formerly known as Oak Hill Bio Ltd). Learn more at oakhillbio.com.
Contacts
Investors:
John Fraunces
LifeSci Advisors
[email protected]
Clinicians:
Brenda Vincenzi
Oak Hill Bio
[email protected]
Media:
[email protected]