Wayne Chadwick Submitted:

Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by loss of function of the maternally imprinted gene UBE3A on chromosome 15. Despite significant research efforts, there remains a considerable unmet need for disease-modifying therapies.

Healx is a clinical-stage, AI-driven biotech company dedicated to accelerating the discovery and development of treatments for rare diseases. At the core of our approach is Healnet, a proprietary AI platform that integrates large-scale multimodal biomedical data to identify novel connections between existing drugs, novel targets, and diseases. This enables target-agnostic, ranked hypotheses for monotherapies and combination therapies at a scale and speed not achievable through conventional discovery approaches.

Candidate hypotheses are validated through a structured translational pipeline, progressing from disease-relevant in vitro models to in vivo efficacy and pharmacokinetic studies to support clinical advancement. We present our Angelman syndrome programme as a case study of this approach.

Following computational identification of candidate compounds, we established an in vitro screening platform using primary mouse neurons. Shortlisted candidates then progressed to in vivo efficacy studies in an Angelman syndrome mouse model, demonstrating significant improvement across key AS-related phenotypes, including reversal of cognitive deficits, improved motor learning and coordination, and increased exploratory activity.

Importantly, all candidate therapies are either approved drugs or previously shelved assets with extensive human safety data. We further demonstrate how a novel reformulation strategy was employed to optimize preclinical tolerability for chronic dosing while enhancing efficacy, supporting progression toward clinical evaluation in individuals with Angelman syndrome.

This work illustrates how an AI-powered discovery approach can rapidly identify and validate promising therapeutic candidates for rare neurodevelopmental diseases, offering the potential to deliver safe and effective treatments to patient communities with significant unmet need.