Chasing optimum First-in-Human dose – welcome to reality!

The Groupe de Métabolisme et Pharmacocinétique (GMP) is hosting a workshop on May 23, 2025, in Paris titled "Chasing Optimum First-in-Human Dose". This workshop will feature renowned speakers and insightful presentations, fostering discussions on key aspects of First-in-Human (FIH) dose selection and optimization.

Workshop overview

Agenda highlights

  • Getting the FIH dose right: Transforming Preclinical Knowledge into Clinical Applications
    Antoine Deslandes, Sanofi
  • Physiologically Based Pharmacokinetics (PBPK) modeling to support First-in-Human studies of small molecules
    François Bouzom, Simulations Plus
  • Knowledge Sharing on specific challenges for FIH dose predictions
    Glenn Gauderat, Servier
  • Working with Probability of Pharmacological Success (PoPS) to Inform FIH Studies
    Martin Bergstrand, Pharmetheus

Pharmetheus session

Dr. Martin Bergstrand, 14.00-15.00, May 23, 2025

Working with Probability of Pharmacological Success (PoPS) to inform First-in-Human studies


The Probability of Pharmacological Success, or PoPS, is a metric to inform early-stage drug development decisions based on benefit and risk data available at the time. In a FIH setting PoPS can for example be used to: (1) prioritize between different candidate assets to decide which one to bring into clinic and (2) select the planned dose range to study in FIH studies.

The PoPS approach was initially introduced by Dr. Chao Chen and colleagues. The approach leverages information about pharmacokinetics (PK), exposure–response (ER) relationships for desired as well as undesired pharmacology (efficacy and safety). In addition, it defines targets for the relevant endpoints (e.g. target engagement and risk of exposure above the no observed adverse effect level). At the stage of FIH the available PKPD information is usually primarily based on in vitro and/or animal studies. These are by nature associated with considerable uncertainty. PoPS allows to account for this uncertainty in a quantitative manner, and to propagate it into an overall probability to meet a multi criteria definition of pharmacological success.

Pharmetheus has extended the original PoPS concept and implemented a template workflow to facilitate efficient and reproducible applications. The template workflow was developed for RStudio and Quarto to allow for a combination of ease of use for simple routine applications and more advanced custom applications.

The presentation will introduce the basic idea of PoPS as well as the template workflow in application to a FIH case-study. For confidentiality reasons this will be a simulated hypothetical example inspired by real case studies. It will also discuss the importance of systematically accounting for uncertainties in planning for FIH studies and the value of a workflow that can be easily updated with emerging information during early drug development.

Event details

Date and time

  • Date: Friday May 23, 2025
  • Time: 09.00-17.15

Location

  • Venue: Wojo Paris 14e – Montparnasse Gaîté – 82 Avenue du Maine Paris 75014

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Organizers

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