Development of Predictive QSPK Models for Novel Biotherapeutics
Happy New Year! Thank you for attending the New Year edition of Boston QSP bi-monthly event on January 10th.
The event featured a talk titled Development of Predictive QSPK Models for Novel Biotherapeutics by our guest speaker Dr. Dhaval K. Shah. The event was moderated by Boston QSP's scientific advisor Dr. Dean Hickman.
Various novel bio-therapeutics such as antibody-drug conjugates (ADCs), bispecific molecules, immuno-oncology agents, and CAR T-cells have emerged as an important and highly promising class of drug candidates. However, they pose tough challenges during various stages of drug development. One of the challenges is the difficulty to predict the absorption, distribution, metabolism, and excretion (ADME) properties. How can we overcome this? Dr. Shah has been trying to find the answer through physiologically based pharmacokinetic (PBPK) and quantitative system pharmacokinetic (QSPK) models. We were able to ask Dr. Dhaval a couple of questions.
BQSP: Why do we need QSPK models for ADCs while there are conventional PK or QSP models?
Dr. Shah: QSPK models allow one to investigate and predict the concentrations of different ADC analytes at the site-of-action. This in-turn leads to the development of more reliable exposure-response relationships for ADCs, as one does not have to assume that plasma concentrations represents the concentrations at the site-of-action. Conventional PK models are not capable of developing such robust relationships as they are limited to characterization and prediction of plasma exposure for the drugs. In addition, QSPK models allow one to characterize the concentration of different ADC analytes at the sub-cellular regions of interest, which facilitates a robust integration with QSP models, as the target biology and drug pharmacology can differ based on a given location within the cell. The current QSP approaches do not take this fact into account.
BQSP: What are the potential pitfalls of QSPK approach for ADCs compared to conventional approaches?
Dr. Shah: One of the main pitfall of the QSPK models is the amount of resources and time it takes to develop a robust QSPK model. One needs to not only understand the whole body disposition of the drug, but also needs to understand the regional distribution in a given tissue and sub-cellular disposition within target cell, to develop a true QSPK model. This requires the availability of reliable analytical methods to quantify drug levels in different biological matrices, availability of imaging techniques to locate drug disposition on a tissue and cellular level, and mathematical expertise to integrate all the measurements using the principles of mass balance.
Redacted version of the presentation is available here.
The next Boston QSP event will be on March 21st. We are finalizing an exciting speaker lineup per usual. RSVP here today to secure your seat. RSVP is free but required.
The event was organized by Boston QSP and sponsored by Amgen.
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About Boston QSP
Boston QSP is a 501(c)(3) non-profit organization whose mission is to foster the sharing of QSP knowledge, challenges, solutions, and opportunities to advance the field as an interdisciplinary community in Boston.