C1A - Differentiated MIDD strategies to accelerate clinical development in metabolic diseases are worth their weight

Sunday, October 19, 2025

11:00 AM - 12:30 PM MDT

Location: Colorado B-D

Co-Chair(s)

Theodore Rieger, PhD

Director
Pfizer Inc, Massachusetts, United States
Brian Schmidt, PhD

Executive Director, Clinical Pharmacology
Madrigal Pharmaceuticals
West Conshohocken, Pennsylvania, United States

Speaker(s)

Karen Schneck, PharmD

PK/PD/Pharmacometrics
Eli Lilly and Company, United States
Rune Overgaard, PhD (he/him/his)

Senior Scientific Director
Novo Nordisk
Virum, Hovedstaden, Denmark
Scott Siler, PhD (he/him/his)

Chief Science Officer, Quantitative Systems Pharmacology
Simulations Plus, United States
Sibylle Neuhoff, PhD (she/her/hers)

Senior Scientific Advisor, Transporter Group Head, Simcyp
Certara Predictive Technologies, United Kingdom

Disclosure(s):

Theodore Rieger, PhD: No relevant disclosure to display

Brian J. Schmidt, PhD: No relevant disclosure to display

Karen Schneck, PharmD: No relevant disclosure to display

Rune Overgaard, PhD: No relevant disclosure to display

Scott Q. Siler, PhD: No relevant disclosure to display

Sibylle Neuhoff, PhD: No financial relationships to disclose

Description of session (include background & scientific importance): The development of incretin therapies based on Glucagon-like Peptide 1 (GLP-1) has been revolutionary for the treatment of type 2 diabetes, obesity, and potentially many other metabolic dysfunction-associated disorders. The pace and importance of this class of therapies may even expand with novel dual- and triple-agonist therapies showing promise clinically. However, every stage of development for these therapies comes with its own challenges. For example, pre-clinical translation of pharmacokinetics and adverse events is imperfect due to limitations on animal models and complex interactions between GLP-1 and gastrointestinal motility. Early in development, there are challenges with extrapolating short-term observations on body weight to real-world efficacy. Optimizing later stage studies may be difficult due to the need to adjust individual patient dosing for tolerability, as well as translating between different indications and populations. We present here perspectives applying empirical and mechanistic approaches to enable efficient clinical development of incretin-based therapies to address these challenges.

Learning Objectives:

Participants will be able to: • Recognize and account for special considerations for modeling obese populations that have been gained empirically and through more mechanistic approaches • Understand some of the significant opportunities for treating obesity and challenges for developing incretin mimetics • Understand emerging therapeutic mechanisms in metabolic diseases • Develop insights into applying modeling to reposition therapeutics between indications where obesity is a substantial co-morbidity • Demonstrate how different modeling approaches facilitate clinical development in this rich field, including PBPK, population pharmacokinetics, exposure-response, PK/PD, and QSP

Presentations:

11:00 AM - 11:22 AM MDT

Pharmacokinetics of incretin mimetics: a forward-looking perspective
Speaker: Karen Schneck, PharmD – Eli Lilly and Company
11:22 AM - 11:45 AM MDT

MIDD for semaglutide – contributions from different modelling approaches throughout the value chain
Speaker: Rune Overgaard, PhD (he/him/his) – Novo Nordisk
11:45 AM - 12:07 PM MDT

Translation of weight loss and prediction of liver pharmacodynamics in NASH across a range of mechanisms by quantitative systems pharmacology modeling
Speaker: Scott Q. Siler, PhD (he/him/his) – Simulations Plus
12:07 PM - 12:30 PM MDT

Considerations for physiologically based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling to facilitate drug development in obese and related specific populations
Speaker: Sibylle Neuhoff, PhD (she/her/hers) – Certara Predictive Technologies