As we close another significant year, we celebrate remarkable achievements and expansions at ESQlabs.

Core Services

Physiologically Based Biopharmaceutics Modeling (PBBM)
At ESQlabs, we continue to develop qualified and flexible modeling approaches that seamlessly integrate with the Open Systems Pharmacology (OSP) platform. Through scientifically rigorous and user-friendly solutions, we address challenges in pharmaceutical development, including the validation of biopharmaceutics IVIVE and virtual bioequivalence (VBE). In 2024, we contributed to exciting projects focusing on oral and ocular drug delivery, supporting optimal formulation development and bridging in vitro data to in vivo scenarios.

Quantitative Systems Pharmacology (QSP) / Quantitative Systems Toxicology (QST)
We remain dedicated to improving drug development and safety evaluations using QSP/QST frameworks. These systems-level models help us better understand complex pharmacological and toxicological processes, guiding translational research and decision-making. As part of our effort, we have been awarded the CRACK IT Virtual Second Species challenge to develop a multi-scale modeling framework for toxicological endpoint predictions in the dog. We leverage next-generation modeling paradigms, recently facilitated by modularization features introduced in MoBi v12, to streamline integration and complexity handling.

Veterinary Medicine
Our commitment to extending PBPK modeling principles to veterinary medicine stands firm. We are refining animal models, with plans to apply rigorous model qualification approaches similar to those established for human PBPK, ultimately improving data-driven decision-making in veterinary drug development.

Next-Generation Risk Assessment (NGRA)
ESQlabs continues to champion NGRA initiatives, contributing to the replacement, refinement, and reduction (3Rs) of animal testing by integrating New Approach Methodologies (NAMs). In 2024, we intensified our involvement in several EFSA- and EU-funded projects:

• EFSA PFAS Project: We explored the immunotoxicity of perfluorinated substances, demonstrating how human-based in vitro systems and computational modeling can deepen our understanding of PFAS effects on immune functions.
• EFSA DNT (Developmental Neurotoxicity) RAP4 Project: As partners in the EFSA DNT RAP4 initiative, we focus on understanding how chemical exposures may affect brain health and development. Under LOT4, we develop Adverse Outcome Pathway (AOP)-based Integrated Approaches to Testing and Assessment (IATA) and conduct four pesticide-focused case studies, harnessing computational modeling to predict DNT outcomes.
• EU Horizon ONTOX Project: We contribute to ONTOX by creating innovative methodologies to predict kidney, liver, and neurodevelopmental toxicity. After establishing a high-throughput PBK mode platform for Tier 1 evaluation of chemical internal exposure, we are now developing more tailored PBK and in vitro kinetic models for priority chemicals. Recently, our colleague Susana Proença shared insights on PBK Modeling and QIVIVE at the ESTIV Training Course hosted by the Luxembourg Institute of Science and Technology (LIST), advancing the dialogue on next-generation toxicokinetics frameworks.
• EFSA ExpoAdvance Project: We are proud to announce the publication of the EU Roadmap for Advancing Aggregate Exposure to Chemicals. This milestone, achieved after a year of rigorous review and stakeholder collaboration, shapes the future of chemical safety by outlining strategies for improved exposure assessments.

Across these projects, our contributions support the regulatory and industrial shift toward more predictive, human-relevant risk assessments, ultimately reducing reliance on animal testing and improving public health and environmental safety.

Platforms

Women’s Health
We developed pregnancy and postpartum PBK models across multiple species and launched a project funded by the Bill & Melinda Gates Foundation, focusing on precise exposure predictions in the female reproductive tract. These breakthroughs pave the way for additional PBK and QSP model extensions in women’s healthcare.

Large Molecule PBPK
We expanded our modeling of bispecific T-Cell engagers and ADCs, improved our understanding of local TMDD, as outlined in our new publication, and initiated large molecule models for pregnancy and lactation. We also broadened our scope toward novel modalities including siRNA, cell therapies, and nanoparticles, ensuring future adaptability in large molecule drug development.

IVIVE Toolset
We initiated the development of an integrated IVIVE toolset that will support key ADME in-vitro assays, enhancing our capacity to translate in vitro data into clinically meaningful predictions.

MPSlabs
MPSlabs became an official business unit, earned a nomination for the Innovation Prize Niedersachsen, launched the DigiLoCs app at EUROoCS, secured key grants (e.g., Berlin Animal Protection Grant, Dypha EIC), and engaged the community via webinars. We look forward to expanding our team, offerings, and impact in the coming year.

Radiopharmaceuticals
A new Radiopharmacology platform led by Dr. Luis David Jimenez Franco now enables PBPK modeling for radiopharmaceuticals, internal radiation dosimetry, pediatric extrapolations, and protocol optimization. With Prof. Gerhard Glatting as Scientific Advisor and initial projects secured, we anticipate continued growth in precision nuclear medicine.

Small Molecule & High-Throughput PBPK
We enhanced community PBPK model repositories, re-evaluated transporter-mediated DDIs, and advanced from rodent IV to oral and human HT-PBPK scenarios. Collaborative efforts with industry and academic partners maintain the relevance and regulatory value of these models, including contributions recognized with a paper award by our colleague René Geci.

Software

This year was pivotal for the Open Systems Pharmacology Software (OSPS):

• OSPS Version 12 & OSMOSES: Together with Bayer and design2code, we introduced OSMOSES modularization into MoBi. This concept streamlines the development of complex models and improves quality control, reusability, and efficiency—unveiled at the first OSP Community Conference in Basel.
• Other Releases:
  • OSPS Version 11.3: Performance improvements and bug fixes.
  • Parameter Identification R Package: A new tool for streamlined parameter identification workflows.
  • rSharp R Package: Facilitates communication between R and .NET, supporting OSP R packages across Windows, Linux, and MacOS.
  • esqlabsR & ESQapp: Our esqlabsR R package standardizes OSP-based modeling workflows and now features a ShinyApp interface (ESQapp), gaining wide acceptance in the pharmaceutical industry.

With OSPS Version 12 providing crucial modularity, we implemented the first lactation and pregnancy modules in a “plug and predict” fashion. As we embark on Versions 12.1 and 13, we remain committed to expanding our software service portfolio—offering tailored R frameworks, delivering qualified cloud environments for OSP-based modeling and simulation, and continually pushing the boundaries of what is possible in computational pharmacology and toxicology.