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.

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