 Dr. Yongliang Fang
Chief Operating Officer
Zhejiang Doer Biologics
China |
Title:
An Integrated Three-Layered Pipeline for Immunogenicity Risk Assessment and Mitigation in Protein Therapeutic Development
Abstract:
The development of anti-drug antibodies (ADAs) remains a significant hurdle in the clinical translation of therapeutic proteins, potentially impacting safety, pharmacokinetics, and efficacy. To address this, a proactive preclinical strategy is essential to de-risk candidates prior to First-in-Human (FIH) trials. We implemented a systematic, three-tiered immunogenicity assessment pipeline:
Tier 1 (In Silico): Computational screening of T-cell epitopes to identify high-risk sequences.
Tier 2 (In Vitro/Ex Vivo): PBMC-based assays to evaluate the functional immune response in human-derived cells.
Tier 3 (In Vivo): Pharmacokinetic (PK) and ADA profiling in cynomolgus monkeys to observe the immune response in a non-human primate model.
We have evaluated the correlation between these three layers across several lead candidates. Each component provides distinct insights into immunogenic potential, with specific strengths and limitations. The value of the pipeline lies not in a single definitive “yes/no” answer, but in the convergence of data to guide protein engineering and lead selection. Although no current preclinical model offers 100% predictive accuracy for human immunogenicity, this integrated pipeline provides a robust framework for ranking candidates. By identifying and mitigating risks early, we can significantly improve the success rate of clinical translation for next-generation biologics.
Biography:
Dr. Yongliang Fang obtained his Ph.D. from Dartmouth College. His main research interests include protein engineering, immunogenicity analysis, protein deimmunization, drug discovery, and clinical translation. As a co-founder and Chief Operating Officer of Occulo Holdings, LLC, he led Occulo’s Series A financing, pipeline development, in-licensing of key assets, and out-licensing of preclinical programs. Currently, he serves as the Chief Operating Officer of Zhejiang Doer Biologics Co., Ltd., where he is primarily responsible for regulatory affairs, clinical translation and operations, and business development for Doer Bio’s innovative biotherapeutics.
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