26th North American ISSX Meeting

Lijuan Hou

From Study Director team, Director of WuXi AppTec DMPK

An ADC primarily consists of an antibody, a linker and cytotoxic payload. Due to its complex structure,  both biotransformation and bioanalysis may present significant challenges. In this presentation, an expert from WuXi AppTec DMPK will share  considerations and detailed information on the biotransformation and bioanalysis strategies for overcoming these challenges.

Oligonucleotides (Oligos) target a variety of disease areas, with delivery strategies posing particular challenges in the CNS field. Early stage proof-of-concept studies and intrathecal dosing can be applied to facilitate oligo delivery to CNS. We will present strategies for addressing CNS-target Oligos, leveraging state-of-the-art technical platforms. 

Learning Objectives: 

1) Gain insights into the strategies used to address the challenges of ADC biotransformation and bioanalysis.

2) Explore oligonucleotide delivery challenges and solutions, particularly in the CNS field.

Lifang Jiang

PhD, From In Vitro ADME team, Associate Director of WuXi AppTec DMPK

With the implementation of the M12 guidance, there has been a standardization of the guiding principles on DDI across various regions. In enzyme-mediated interactions, further emphasis has been placed on research related to CYP and UGT enzymes. The accuracy and predictive power of in vitro data are extremely important for better clinical drug interaction predictions. Among them, time-dependent inhibition (TDI) of CYP enzymes is a significant area of focus, and there has been extensive industry discussion in the feedback on the M12 guidance, particularly about whether TDI should use the dilution or non-dilution method. Data generated from our lab from the non-dilution method for CYP TDI evaluation has been shared with the agency during the feedback phase, resulting in the inclusion of the non-dilution method in the M12 guiding principles. In this presentation, we will review this data. We will also share a cost-effective method for evaluating UGT inhibition using human liver microsomes.

Learning objective:  

1.Why is the non-dilution method for evaluating CYP TDI in the Discovery phase at least as effective as dilution method?

2.Advantage of using human liver microsome to evaluate UGT inhibition.