The goal of pre-clinical development is to bridge the transition from lead compounds to clinical candidates by comprehensively characterizing safety, efficacy, and pharmacological properties. Once a lead compound demonstrates promising activity in disease models, it enters pre-clinical development where rigorous assessments establish whether the candidate is safe and suitable for first-in-human studies.

In vitro pharmacological experiments

In early development we perform a broad range of in vitro pharmacological experiments to characterize the potency, efficacy and safety profile of lead compounds. These studies include concentration–response analyses, target binding kinetics, and resistance assays in infectious diseases to refine the mechanism of action. Disease model assays include higher-throughput measurements of infection and hollow-fiber assays to mimic dynamic exposure profiles, as well as early toxicity experiments in disease-relevant cellular models. LED3 facilities to these purposes include high-throughput plate readers at different bio-safety levels, as well as high-throughput imaging microscopes in the Cell Observatory.

In vivo PK and PD experiments

To understand how potential drugs behave in vivo, we conduct pharmacokinetic (PK) and pharmacodynamic (PD) studies in appropriate animal models of disease. PK studies quantify absorption, distribution, metabolism and excretion, providing key parameters such as exposure, clearance and half‑life. Advanced techniques including microdialysis sampling and multi-level longitudinal designs are employed to capture the dynamic interplay between drug exposure and pharmacological response across tissue compartments. Ultra-sensitive LC-MS/MS facilities at LACDR including MAC are available for PK and metabolite studies. PD studies link these exposures to biomarker changes and functional efficacy read-outs from biochemical, molecular, culture-based, or imaging assay. Combining these datasets allows us to define exposure–response relationships, explore dose ranges, and identify potential efficacy and safety targets to support dosing and design of first‑in‑human studies. An example of innovative animal models of disease is the zebrafish embryo/larva in which IBL and LACDR have extensive experience. Mechanisms of disease are studied using transgenic disease models, fluorescence reporter lines, and pharmacology is quantified at high-throughput rates through for example fluorescence imaging, to establish translational PKPD relationships.

PKPD modelling

Experimental PK and PD data are integrated using quantitative PKPD modelling to describe and predict the time course of drug concentrations and effects. These models help to quantify target engagement, characterize hysteresis between exposure and effect, and distinguish between direct and indirect response mechanisms. By simulating alternative dosing regimens and scenarios, PKPD models iteratively support rational dose selection for further preclinical studies (learn-confirm) and inform starting doses and escalation schemes for early clinical trials. Several high performance computational clusters are leveraged for these modelling activities.

To enhance clinical translation, we extend our modelling and simulation approaches to special populations and clinical settings. Through quantitative modelling, we can evaluate expected dosing requirements and variability in special populations such as paediatric, elderly, renally or hepatically impaired, and other vulnerable patient populations. These clinical modelling activities support the design of adaptive and efficient early‑phase trials, optimization of sampling strategies, and the refinement of dosing recommendations as compounds progress towards late‑stage development and registration.

PBPK and QSP modelling

Physiologically based pharmacokinetic (PBPK) and quantitative systems pharmacology (QSP) modelling are excellent tools to gain mechanistic insight into drug behaviour and disease biology. PBPK models combine compound‑specific properties with detailed physiological parameters to predict tissue distribution, organ exposure and the impact of intrinsic factors such as age, organ impairment or drug–drug interactions. QSP models integrate pathways, biomarkers and clinical endpoints into a coherent systems-level framework, enabling in silico experiments that link molecular interventions to patient‑level outcomes, including simulating virtual twins, and guide biomarker strategy and clinical trial design.

Formulation sciences

Formulation science in early development focuses on designing drug products that are stable, manufacturable and suitable for the intended route of administration, while preserving the integrity and activity of small molecules and complex modalities such as biotherapeutics. This includes selecting excipients and delivery systems that protect sensitive molecules, and engineering advanced carriers (for example nanoparticle and polymer-based systems) to enable targeted and patient-friendly delivery. By linking detailed physicochemical and biophysical characterization to in vitro and in vivo performance, formulation research supports robust manufacturing, extended shelf life and reliable clinical performance across diverse patient groups.