Oak Hill Bio Spotlights Publication Detailing Discovery and Initial Development of Rugonersen in Nucleic Acids Research

September 09, 2025 at 08:00 AM EDT

Oak Hill Bio, a biotechnology company committed to developing life-changing therapies for rare diseases, today announced the publication of a peer-reviewed article describing the discovery and early preclinical development of rugonersen (OHB-724), an investigational antisense oligonucleotide being developed for Angelman syndrome.

The article, titled “Angelman syndrome patient-derived neuron screen leads to clinical ASO rugonersen targeting UBE3A-ATS with long-lasting effect in monkeys” has been published in Nucleic Acids Research (https://doi.org/10.1093/nar/gkaf851).

The publication describes how rugonersen was discovered and details the strong pre-clinical data that supports clinical development.

Key highlights from the publication include:

Discovery approach: Appoximately 2,500 LNA-modified antisense oligonucleotides (ASOs) were screened in Angelman syndrome patient iPSC-derived neurons. Rugonersen was selected as a clinical lead due to highly favorable potency, efficacy, and safety profiles.
Potent pharmacology: Nonhuman primate experiments demonstrate potent down-regulation of UBE3A-ATS, upregulation of UBE3A mRNA, and UBE3A protein in key brain regions.
Durable effects and dosing rationale: Nonhuman primate studies showed sustained pharmacology after up to three intrathecal doses with no adverse effects, supporting infrequent dosing in clinical development.
Rugonersen exhibited superior in vitro potency in inhibiting UBE3A-ATS and upregulating UBE3A mRNA compared to two ASOs similar to those in clinical development.

Strong preclinical foundation for the development of rugonersen in AS

“This tour-de-force research publication highlights the strong scientific foundation for rugonersen’s clinical program,” said Ben Philpot, Ph.D., an Angelman syndrome researcher at the University of North Carolina. “By demonstrating selective UBE3A-ATS knockdown and restoration of UBE3A protein across human patient-derived neurons—and durable effects in nonhuman primates—the work provides a clear translational rationale for rugonersen. We would expect that greater restoration of UBE3A protein would translate into improved therapeutic outcomes.”

About Angelman syndrome

Angelman syndrome is a rare neurodevelopmental condition caused by loss of UBE3A function in neurons, leading to profound developmental delay, seizures, lack of speech, and motor impairment. There are currently no approved disease-modifying treatments.

About Oak Hill Bio

Oak Hill Bio is a clinical-stage biotechnology company dedicated to developing life-changing therapies for people with rare diseases. Its pipeline includes late-stage programs in Angelman syndrome and complications of extreme prematurity, as well as a preclinical asset for diabetic macular edema. For more information, visit www.oakhillbio.com.