CNS toxicity remains one of the leading causes of failure in drug development, yet it is rarely detected in preclinical studies. Among these risks, seizure liability is one of the most challenging and regulatory-critical CNS adverse effects to predict.

In this webinar, 28bio presented findings from the Endurance Study, a retrospective, non-interventional study evaluating the predictive performance of CNS-3D Brain Organoids in small molecules with documented human clinical outcomes from 120,551 patients and known positive controls. The study focused on seizure liability, one of the most challenging and regulatory-critical CNS adverse effects to predict in neurological drug development.

Top-line results showed 83% sensitivity and 89% specificity in predicting clinical seizure liability across seizure-inducing drugs and clinically safe drugs, outperforming animal models with a 13x higher predictive performance¹.

The Endurance Study results also outperformed previously published data on 2D and 3D cell-based assays and were in line with guideline recommendations from regulatory agencies.

In addition, the webinar presented new data extending these findings across other modalities. This included results showing 92% sensitivity and 92% specificity in classifying neurotoxic and well-tolerated antisense oligonucleotides (ASOs), as well as data demonstrating how CNS-3D Brain Organoids detected disruption of neural network activity in AAV systems at doses below overt cytotoxicity, revealing functional risk earlier than traditional viability-based assays.

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Key Takeaways
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• Predicted clinical seizure liability with high accuracy: 83% sensitivity and 89% specificity in small molecules using CNS-3D Brain Organoids  

• Extended predictive insights across modalities: Data in ASOs and AAVs demonstrated consistent performance beyond small molecules  

• Detected functional neurotoxicity earlier: Identified network-level disruption before cell death, enabling better CNS safety decisions  

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Speaker
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Chris Butt, PhD
VP of Technology at 28bio

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Chris Butt is Vice President of Technology at 28bio, where he leads the company’s scientific strategy. He has a background in translational neuroscience and in vitro model systems, with a focus on studying neurological outcomes relevant to drug development.