MS08 - OTHE-08

Quantitative Systems Pharmacology: Linking mathematical biology to model informed drug development (MIDD) - Pharmacometrics Subgroup (Part 2)

Friday, July 18 at 10:20am

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Note: this minisymposia has multiple sessions. The other session is: and Part-1.

Marissa Renardy (Quantitative Systems Pharmacology, GSK), Kathryn G. Link, Quantitative Systems Pharmacology, Pfizer Inc.

Description:

Quantitative systems pharmacology (QSP) combines mathematical and computational modeling tools with mechanistic understanding of biology and pharmacology to guide drug discovery and development. QSP is used in the pharmaceutical industry to accelerate and de-risk drug discovery and development across multiple stages, from target discovery/validation to clinical trial design to lifecycle management. In recent years, QSP has been increasingly used in regulatory submissions for clinical trials across many therapeutic areas (PMID:34734497). In this session, speakers will present recent advances and perspectives in the field of QSP. This minisymposia will have two sessions. The first session will consist of four technical talks. The second session will be comprised of three technical talks and an industry panel discussion with prepared and audience-driven questions.

Farrah Sadre-Marandi

qPharmetra

"Navigating pediatric dose selection: Insights from nifurtimox for Chagas disease"

Pediatric dose selection presents unique mathematical and pharmacological challenges due to developmental changes in drug absorption, distribution, metabolism, and excretion (ADME). In the context of Chagas disease—a neglected tropical disease affecting children across Latin America—this talk presents a quantitative framework used to support the regulatory approval of nifurtimox in pediatric populations. This talk will focus on the mathematical modeling strategies that informed dose selection, highlighting the integration of population pharmacokinetics, allometric scaling, and exposure-response analysis. We explore the nonlinear mixed effects modeling approach applied to sparse clinical data across a wide pediatric age and weight range, and we demonstrate how simulation-based techniques were used to evaluate dose-exposure relationships and optimize weight-band dosing strategies.

Sarah Minucci

Certara

"A Quantitative Systems Pharmacology Platform Model of Alzheimer's Disease for Reducing Amyloid Plaque and Tau"

Alzheimer's Disease (AD) is a neurogenerative disease that progressively impacts cognitive function, characterized by the buildup of amyloid-beta (Aβ) and tau into plaques and neurofibrillary tangles (NFTs), respectively. AD is currently ranked as the seventh leading cause of death in the United States. It has been shown that the removal of Aβ plaques as well as the reduction in tau biomarkers can reduce cognitive decline in AD patients. Furthermore, anti-Aβ treatments have shown effects on tau pathology, indicating a complex interplay between these two proteins and their role in the development of AD. Quantitative systems pharmacology (QSP) models have been developed in the field of AD to understand the impact of plaques and NFTs in disease progression and their responses to therapeutic modulation. We developed a platform QSP model of Aβ and tau pathology in AD and the effects of anti-Aβ and anti-tau therapies on various biomarkers in order to better understand the interplay of Aβ and tau and test potential strategies for mono- and combination anti-Aβ and anti-tau therapies. Current hypotheses regarding tau pathology spreading, NFT formation, and amyloid re-accumulation after depletion were tested throughout model development. The model was calibrated/benchmarked to >70 clinical biomarker datasets to capture disease progression as well as PK and Aβ/tau biomarker changes in response to anti-Aβ mAbs lecanemab, gantenerumab, donanemab, and aducanumab as well as tau-targeting ASO BIIB080. Model simulations were in good agreement to Aβ, tau, and PK data, including plaque reaccumulation after treatment and the effects of anti-Aβ therapy on tau pathology.

Sarah Minucci, Olivia Walch, Farrah Sadre-Marandi, Marissa Renardy

Certara, Arcascope, qPharmetra, GSK

"Industry Panel Discussion"

Quantitative systems pharmacology (QSP) combines mathematical and computational modeling tools with mechanistic understanding of biology and pharmacology to guide drug discovery and development. QSP is used in the pharmaceutical industry to accelerate and de-risk drug discovery and development across multiple stages, from target discovery/validation to clinical trial design to lifecycle management. In recent years, QSP has been increasingly used in regulatory submissions for clinical trials across many therapeutic areas (PMID: 34734497). In this session, speakers will present recent advances and perspectives in the field of QSP. The second session will be composed of two technical talks and an industry panel discussion with prepared and audience-driven questions.

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Annual Meeting for the Society for Mathematical Biology, 2025.