In Vivo PK/PD Platform

Innovative in vivo PK/PD platform using NHP and hFcRn mouse models to precisely characterize biologics candidates

Integrated In Vivo PK/PD Characterization Platform with NHP and hFcRn Mouse Models

Zhili Yao, Yuanyuan Zheng, Haiqing Chen, Jinchao Tan, Yixia Qian, Jiansheng Wu WuXi Biolo gic s , N O .24 0 H edan Ro ad , Pudon g Ne w Distri c t , Sh an gh ai , Chi na (Co nta ct: P S _BD@wu x i b iolo gic s .com)

Abstract Traditional in vivo studies often involve separate teams handling testing, assay development, and bioanalysis, which can lead to communication delays and missed opportunities for lead optimization. To address this, WuXi Biologics has developed an integrated, end-to-end in vivo PK/PD platform designed to streamline preclinical candidate (PCC) development for clinical applications. This PK/PD platform serves as a comprehensive, one-stop solution for screening lead molecules through dose-concentration-response studies across multiple species, including non-human primates (NHPs) and hFcRn mouse models. With extensive project expertise, rapid response times, and flexibility tailored to client needs, our PK/PD team efficiently delivers high-quality data and insightful interpretations to accelerate early-stage drug development.

Case Study: Comprehensive PK/PD and Safety Evaluation of T-Cell Engagers (TCEs) in NHP Models In this case study, PK/PD and dose-related toxicity were analyzed for TCEs in NHP models. The results revealed a unique PD effect pattern, where the PD response was not proportional to the PK response. 7666 =?8 " # #

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Fig 1. Integrated In Vivo PK/PD Characterization Platform

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• Total Timeline: 6-11 weeks • Rapid Response: Monkeys scheduled within 7 days • Highly Customized Assay Development • Flexibility: Accommodation of specific client requirements • Data interpretation: Insightful analysis for integrated projects

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The integrated platform confirmed a rapid in vivo PD response. Results demonstrated a unique PD effect of TCE, with a lack of proportionality to the PK response. Case Study: In Vivo PK and Eicacy Evaluation of Antibody-Drug Conjugates (ADCs) In this case study, the PK of intact ADCs and the average drug-to-antibody ratio (DAR) were evaluated in vivo . The dose-concentration-response relationship for efficacy was also determined using CDX models, designed based on tumor target validation through immunohistochemistry (IHC).

Fig 2. Key Features of PK/PD Platform using NHP/hFcRn Mouse Models 2 Weeks for Animal Ordering and Quarantine 3-4 Weeks for In Vivo Sampling 2-3 Weeks for Bioanalysis

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PK Analysis confirmed molecular integrity and evaluated average DAR of ADCs.

Rational design of CDX model offers predictable efficacy data for ADCs

Enzymatic Hydrolysis + LC-MS analysis

Conclusions WuXi Biologics has developed an innovative in vivo PK/PD platform using NHP and hFcRn mouse models to precisely characterize biologics drug candidates. Our innovative technology enables comprehensive, one-stop evaluation of PK, PD, toxicity, and efficacy profiles. With flexible, integrated, and efficient solutions, we are committed to addressing diverse customer needs and setting new industry standards for excellence in early-stage drug development. • • Acknowledgments We thank all scientists from WuXi Biologics CRO Services Department for their great support during the devel- opment of the PK/PD platform. We also thank the legal department, public relations department and market- ing department for their help in patent filing and poster preparation and revision. All experiments were conducted within the CRO Services Department of GBR at WuXi Biologics. For PK analysis, we developed a variety of assays based on ELISA methods, utilizing different matrices from animal models. Capture antibodies or antigens were precoated onto plates, followed by incubation with plasma or serum samples. After washing, the plates were incubated with detection antibodies for quantification. For ADCs, the average drug-to-an- tibody ratio was analyzed using LC-MS after immunoprecipitation and enzymatic hydrolysis. For PD studies, the analysis of receptor occupancy (RO%) and in vivo biomarkers was performed using flow cytometry (FACS). Method

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Results Case Study: Established Model to Simulate Human/NHP PK for Fc Engineering In this case study, the PK of Fc-engineered therapeutic antibodies with enhanced binding were evaluated in humanized FcRn (hFcRn) mice. The observed extended half-life (t1/2) and improved clearance data demonstrate that this model effectively simulates human and NHP PK, providing a robust foundation for Fc engineering studies.

F&G )2,HI J2+, Fig 4. PK Curve of hFcRn Mice (IV infusion) for Evaluating Wild-Type and Fc-Engineering Variants

Fig 5. Clean Gene Background of hFcRn Mice

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WuX i Biolo gic s is a g l ob al leadin g C ontra ct R esear ch, De v elo pm ent and Manu f a c turin g Or g ani z ation (CR DMO ) o ffe rin g end - to - end solutions to ena b le p artners to dis c o v e r, de v elo p and m anu f a c ture b iolo gic s f ro m c on cep t to c o mm er ci ali z ation . About WuXi Biologics Fo r m ore in f or m ation see us at wuxibiologics.com

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To discuss this poster: PS_BD@wuxibiologics.com

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