Functional Neural Activity as a Predictor of CNS Toxicity Across Modalities

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 will present findings from the Endurance Study, is 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 focuses on seizure liability, one of the most challenging and regulatory-critical CNS adverse effects to predict in neurological drug development.

Top-line results show 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 outperform previously published data on 2D and 3D cell-based assays and are in line with guideline-recommendations from regulatory agencies.

In addition, we will present new data extending these findings across other modalities. This includes 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 can detect disruption of neural network activity in AAV systems at doses below overt cytotoxicity, revealing functional risk earlier than traditional viability-based assays.

Learning Objectives:

• Predict clinical seizure liability with high accuracy: 83% sensitivity and 89% specificity in small molecules using CNS-3D Brain Organoids
• Extend predictive insights across modalities: New data in ASOs and AAVs demonstrate consistent performance beyond small molecules
• Detect functional neurotoxicity earlier: Identify network-level disruption before cell death, enabling better CNS safety decisions