Fully human Generative AI HCAb Model

Built on the Harbour Mice^® platform, Harbour BioMed launched the world’s first fully human Generative AI HCAb (Heavy Chain-Only Antibody) Model, accelerating the development of innovative therapies. This model establishes a closed-loop process integrating AI design, intelligent screening, and wet-lab validation.

Training Data

The AI HCAb Model is trained on 9 million NGS-derived HCAb sequences and extensive public data. It uses a fine-tuned protein large language model for de novo generation of high-potential HCAb sequences with secondary optimization for target specificity.

Screening Process

• AI Classification Model to filter non-HCAb sequences
• Multimodal AI Developability Prediction Model (achieving SOTA performance) to assess stability, solubility, and aggregation tendency

Validation Results

Among the 107 de novo generated binder sequences produced:

• 78.5% successfully hit the target
• 20 molecules validated in wet-lab assays showing high activity, purity, yield, and specificity
• Average yield exceeded 700 mg/L
• Multiple candidate sequences showed nanomolar-level binding affinity while maintaining binding activity against relevant targets in both humans and cynomolgus monkeys

Applications

The AI HCAb Model is designed to accelerate development in:

• Multi-specific antibodies
• XDCs
• In vivo CAR-T
• Inhaled or oral large-molecule drugs