UBE3A

Rugonersen, a novel RNA antisense oligonucleotide (ASO), has potential to be the first approved disease-modifying treatment for a disease affecting 500K individuals globally Encouraging clinical efficacy results on exploratory endpoints related to brain function and measures of cognition and communication support further investigation Pivotal Phase 3 study anticipated to be initiated in early 2026 CAMBRIDGE, MA, USA I April 15, 2025 I Oak Hill Bio, a biotechnology company focused on acquiring and developing life-changing rare disease therapeutics, has entered into an exclusive license agreement with Roche (SIX: RO, ROG; OTCQX: RHHBY) to obtain global rights for rugonersen (RO7248824). Rugonersen is an ASO designed as a potential best-in-class treatment for individuals with Angelman syndrome, a rare, genetic neurodevelopmental condition for which there is no approved disease-modifying treatment. Oak Hill plans to initiate a Phase 3 study in early 2026. “We are excited to take on this program. We are incredibly impressed by the rigorous research Roche has conducted, and the promising clinical data generated to date,” said Josh Distler, Chief Executive Officer of Oak Hill. “We have also been moved by the dedication of the patients, families, and investigators in the Angelman community and look forward to working closely with them to fully evaluate rugonersen’s potential to improve the lives of individuals with Angelman syndrome and their families.” “I am very glad that the development of rugonersen will continue,” said Elizabeth Berry-Kravis, M.D., Ph.D., Pediatric Neurologist and Principal Investigator of the TANGELO trial at Rush University Medical Center. “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. We are very excited that the potential benefits of rugonersen will continue to be evaluated for these and other patients with Angelman syndrome.” Angelman syndrome affects an estimated 500,000 individuals worldwide. It typically presents during early childhood and is characterized by cognitive and developmental issues, including speech and communication difficulties, motor impairment, balance issues, and debilitating seizures. The condition is caused by a loss of function of the maternally inherited UBE3A gene. “We are incredibly excited and deeply grateful to see Oak Hill stepping in to continue the rugonersen program for Angelman syndrome. We, along with caregivers and providers, have seen the promise of rugonersen to help those with Angelman syndrome. This is a powerful signal to our community who have fought tirelessly for progress. Knowing that this work will continue means everything. We’re thankful for Oak Hill’s commitment to the community and for recognizing the urgent, unmet needs of individuals living with Angelman syndrome. The community stands ready to support this important effort in every way we can,” said Amanda Moore (CEO, Angelman Syndrome Foundation, ASF) and Ryan Fischer (COO, Foundation for Angelman Syndrome Therapeutics, FAST). About rugonersen Rugonersen is a novel RNA antisense oligonucleotide (ASO) developed as a potential treatment option for individuals with Angelman syndrome, a rare genetic neurodevelopmental condition that affects the central nervous system and causes severe physical and learning disabilities. Rugonersen has been designed to modify disease progression by boosting expression of the paternal version of the UBE3A gene. In the TANGELO study, an open-label, non-randomized, adaptive study led by Roche, rugonersen demonstrated encouraging exploratory effects compared to natural history on multiple clinical measures and on a pharmacodynamic biomarker of brain function, EEG delta power. These data were presented at FAST’s Annual Global Science Summit in November 2024 . Oak Hill believes these results support rugonersen’s potential to address multiple disease domains. Pending review of the final Phase 3 protocol by regulatory authorities, Oak Hill anticipates initiating a pivotal Phase 3 trial in early 2026 for rugonersen as a potential treatment for individuals with Angelman syndrome. About Oak Hill Bio Oak Hill Bio Ltd is a clinical-stage biotechnology company focused on acquiring and developing life-changing rare disease therapeutics. The company’s pipeline includes three programs in late-stage clinical development – potential treatments for Angelman syndrome and complications of extremely premature birth – as well as a preclinical program for diabetic macular edema. Oak Hill has operations in the United States and the United Kingdom. For more information, visit the company’s website at www.oakhillbio.com . SOURCE: Oak Hill Bio

Roche devastated the Angelman syndrome community in 2023, when it ended clinical development of rugonersen, a treatment candidate for the rare neurodevelopmental condition. But after losing a potential acquirer for the drug last year, the Swiss pharma giant has found new life for the drug. Oak Hill Bio is picking up rugonersen and aims to dose the first patient in a Phase 3 trial in the first quarter of 2026, the small biotech exclusively told Endpoints News . Oak Hill and Roche declined to disclose terms of the deal. “This is a positive step forward for patients living with Angelman syndrome and their families,” a Roche spokesperson said in an emailed statement. Angelman leads to severe developmental delays, leaving many unable to speak. The rare condition is thought to impact about 500,000 people worldwide, and is the result of a mutation in a gene inherited from a person’s mother. With rugonersen, an antisense oligonucleotide, Roche hoped to boost the paternal version of the gene, called UBE3A, in the central nervous system. But the pharma company stopped development of the treatment in early 2023 because it “did not meet Roche’s internal criteria.” At least 10 other Angelman treatment candidates have been stopped in recent years. Roche continues to develop a different type of drug, a small molecule called alogabat, for the condition. “When we looked at the data,” Oak Hill CEO Josh Distler said in an interview, “we concluded very rapidly that there was really promising data and it was desperately needed.” The Cambridge, MA-based biotech will be at least a few quarters behind Ionis and Ultragenyx in the development of an antisense oligonucleotide for Angelman. Ultragenyx dosed the first patient with its candidate, called GTX-102, in December, and Ionis plans to start its own Phase 3 for its candidate ION582 in May, according to the study entry in the federal trials database. “We benefit from a couple companies that have gone before us. We’ve been able to look at what they’ve done, and there’s some advantages of not being the first mover,” Distler said. The company is working with clinical investigators and patient groups and will share its Phase 3 design later this year, Distler said. Late-stage development may be a tall task for Oak Hill, which has said little about its funding to date. The company emerged in 2022 with rare disease drug candidates from Takeda . The company is backed by a family office, but Distler declined to disclose the investor’s name. Oak Hill is also working off of money it’s receiving as part of a license and development agreement with Chiesi for an experimental drug for complications of extremely premature birth. The partners didn’t disclose terms of that January 2024 deal.

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Quiver Bioscience (“Quiver”), a discovery technology and therapeutics company advancing programs for the treatment of serious central nervous system (CNS) disorders, announces today a collaboration with the Dup15q Alliance to advance an antisense oligonucleotide (ASO) therapeutic program for chromosome 15q duplication (Dup15q) syndrome using Quiver’s innovative “Genomic Positioning System” (GPS). There are currently no disease-modifying treatments for Dup15q, which remains a substantial unmet medical need. Dup15q is a neurodevelopmental disorder characterized by moderate-to-severe hypotonia, motor and language delays, intellectual disability, epilepsy, and autism spectrum disorder (ASD). Most Dup15q individuals experience seizures and are at an increased risk for sudden unexpected death in epilepsy (SUDEP). Dup15q is associated with genomic copy number variations that result in increased levels of the UBE3A gene product. Dup15q syndrome is clinically related to Angelman syndrome (AS), a distinct neurodevelopmental disorder caused by UBE3A loss of function. ASO therapeutics for AS are currently in clinical trials and have shown early potential benefits in disease modification. The current prevalence estimates for Dup15q syndrome are as high as 1 in 4,000 live births. Genetic medicine approaches, such as ASOs, to reduce UBE3A levels are a viable precision therapeutic path for the treatment of Dup15q and have disease-modifying potential. Quiver has leveraged its unique GPS platform, which integrates unique-in-world, scalable, human single-cell neuronal electrophysiology data with artificial intelligence and machine learning (AI/ML) analytics, and extensive experience in ASO design to robustly model Dup15q syndrome and identify, optimize, and advance effective ASO candidates capable of reducing UBE3A and rescuing associated human Dup15q patient-specific cellular phenotypes. This initial grant formalizes a growing partnership between Quiver and the Dup15q Alliance that has been built over several years. The grant will support requisite preclinical studies to characterize Quiver’s lead therapeutic candidate ASOs and advance towards a transformative treatment for the Dup15q community. “We’re thrilled to continue working shoulder to shoulder with the excellent team at the Dup15q Alliance in advancing this important therapeutic for the community of patients and their families,” says Graham Dempsey, Ph.D., Founder and Chief Scientific Officer at Quiver Bioscience. “This is a devastating disease,” says Mike Porath, Executive Director of the Dup15q Alliance. “We are committed to developing a therapeutic treatment so people with Dup15q syndrome can thrive. We're excited to partner with Quiver to reach our ambitious goals as quickly as possible.” About Quiver Bioscience Quiver Bioscience is a technology-driven company established to create transformational medicines for the brain while simultaneously uncovering new biology and novel, effective drug targets. Using advanced single-cell imaging and multi-omics, we are building the world's most information-rich neuronal insight map via our "Genomic Positioning System". Our approach integrates cutting-edge scalable human models, state-of-the-art technology and proprietary engineering, and learning and surrogate AI/ML models to identify novel therapeutic targets and the best candidate molecules to deliver new and meaningful therapeutics to patients. For information, including additional publications describing the application of Quiver’s GPS to drug discovery, visit www.quiverbioscience.com. About Dup15q Alliance The Dup15q Alliance is a nonprofit organization devoted to bringing awareness to Dup15q syndrome and empowering individuals living with the condition by supporting scientific and clinical research towards effective therapeutics. Media: Noélle Germain +1-617-396-3611 noelle.germain@quiverbioscience.com ‍