FIGON DMD

Michael Cloesmeijer

PhD Candidate, Amsterdam UMC

Michael Cloesmeijer is a PhD candidate at Amsterdam UMC under the supervision of Dr. Marjon Cnossen and Prof. Dr. Ron Mathôt. He earned his Bachelor of Science (BSc) and Master of Science (MSc) degrees in Bio-Pharmaceutical Sciences from Leiden University. During his academic journey, Michael developed a keen interest in pharmacometrics, with a specific focus on the development of population pharmacokinetic models for analgesics and sedatives during his master’s program.

Currently, Michael’s PhD research is part of the SYMPHONY consortium, which is dedicated to personalizing treatment for patients with inborn bleeding disorders. In this consortium, his work revolves around the validation and optimization of pharmacokinetic-guided dosing strategies for individuals with bleeding disorders. Additionally, he is involved in the development of Physiologically Based Pharmacokinetic (PBPK) models. His PBPK modeling research specifically investigates how target binding influences the pharmacokinetics of clotting factor concentrates. This area of study is vital for understanding how clotting factors interact with the body and ultimately, how dosing can be tailored to optimize treatment outcomes for patients with bleeding disorders.

Presentation: Physiologically–based pharmacokinetic modelling of recombinant factor IX Fc fusion protein (rFIXFc) to characterize the binding to type 4 collagen

Patients with severe Haemophilia B receive FIX prophylaxis to prevent bleeding by maintaining a predefined FIX plasma trough level. Recently, chemically modified FIX concentrates with extended terminal half-lives (EHL-products) have been developed. One such EHL-concentrate is recombinant FIX coupled to the human IgG1 Fc domain (rFIXFc). This require less frequent dosing to maintain target FIX plasma trough levels. This has the potential to improve patient compliance and quality of life.

However, rFIXFc has a rapid distribution phase, which is possibly due to binding to the neonatal Fc-receptor (FcRn) and to type IV collagen in the extravascular space. The activity levels of rFIXFc in the extravascular space seem to be crucial, since its hemostatic effect is present even with no measurable FIX activity levels in plasma. In this research we aim to quantify rFIXFc in the extravascular space of various tissues by using physiologically-based pharmacokinetic modelling.