QSP-Copilot: An AI-Augmented Platform for Accelerating Quantitative Systems Pharmacology Model Development.

Quantitative Systems Pharmacology (QSP) is a powerful approach to provide decision-making support throughout the drug development process. QSP comes with many challenges in model development, validation, and applications. Traditional QSP workflows are limited by slow knowledge integration, labor-intensive model construction, inconsistent validation practices, and restricted scalability. In this work, we introduce QSP-Copilot, the first end-to-end AI-augmented solution designed to improve QSP modeling workflows by integrating a multi-agent system utilizing large language models (LLMs). QSP-Copilot provides modular support from project scoping and model structuring to model evaluation and reporting. Through the automation of routine tasks, QSP-Copilot reduces model development time by approximately 40% and improves methodological transparency through systematic documentation of literature sources and modeling assumptions. We demonstrate QSP-Copilot's application for two rare diseases of blood coagulation and Gaucher disease. In the blood coagulation case, automated extraction from ten peer-reviewed articles yielded 179 biological entity interaction pairs; out of these, only 105 unique mechanisms were retained after standardization. For Gaucher disease, screening nine articles produced 151 pairs, which were consolidated into 68 distinct biological interactions following the same post-processing workflow. The extraction precision for blood coagulation and Gaucher disease is 99.1% and 100.0%, respectively. QSP-Copilot extractions can be incorporated into effect diagrams with minimal expert filtering, significantly reducing the manual curation burden. The integration of AI-augmented workflows like QSP-Copilot represents a pivotal shift toward enhanced scalability and impact for QSP across the drug development pipelines, especially in disease areas where biological knowledge is sparse, such as rare diseases.