Biologics are challenging molecules that require extensive characterisation for them to be developed. Formulation plays a key role in enhancing the stability profile of biologics, but to risk mitigate late-stage development, studies such as developability are critical to ensure manufacturable candidates are advanced. The presentation will focus on the importance of developability during drug development and touch on a novel class of molecules that require unique approaches to deliver.

The ACE2-Fc fusion proteins are biotherapeutic candidates that can potently neutralize viruses using the ACE2 receptor to infect cells. In this presentation, I will discuss considerations for the development, analytical characterization, and formulation development of engineered ACE2-Fc drug candidates.

Stabilising proteins remains challenging to formulators. Mutation, reformulation, or switching between liquid, solid, or immobilised presentations can improve stability but are guided only by approximate rules of thumb. By combining these approaches, a wide range of products were generated and characterised using higher-order structure analyses (LC-MS, NMR) and simulations. Case studies from established and novel products, including antibody coformulations, reveal some of the specific mechanisms governing conformational stability, dynamics, and aggregation propensity. The goal is that this understanding will lead to better prediction of potential mutations and formulations for new proteins.

The nanoformulation of therapeutics has gained new momentum with the COVID-19 pandemic. By allowing the rational design of complex architectures and the incorporation of bio-responsive and targeting moieties, nanoformulations have the potential to improve the clinical outcomes of free drugs and navigate biological barriers that are disease-specific and sometimes heterogeneous across patient populations. This talk will give an overview of my recent work using nanocarrier-mediated combination therapy for bacterial infections.

Still today, excipients and excipient mixtures within liquid and lyophilized biopharmaceutical formulations are mainly identified based on excipient screening, or heuristic approaches. Physically-sound modeling approaches, especially predictive modeling approaches are thus desirable to identify excipients and excipient mixtures based on intermolecular interactions in solution with a minimal set of experimental data. This allows to access mutual interactions of multi-excipient systems and to determine the optimal excipient mixture for a given liquid / lyophilized formulation in an early development stage.

Formulating successful therapeutic proteins requires laborious optimization of multiple biophysical properties in a vast design space. In combination with time- and cost-efficient experimentation, artificial intelligence is emerging as a powerful tool to accelerate the optimization of formulations. This talk highlights our efforts to develop high-throughput technologies to assess interfacial stability and provides an example of their synergistic application with machine learning to find optimal buffer conditions for a target protein.

We have derived a predictive model for nanomedicines (polymersomes)-cell association. Our model considers the nanomedicine interaction with the cell glycocalyx, shedding light on the effect of this barrier on polymersomes’ binding and viral attachment to the cell. Experimental validation of the model shows that the nanomedicine/viral-cell binding energy is a highly non-linear function. Our model enables the rational design of phenotypic nanomedicines, allowing us to tune their cell avidity.

Protein aggregates may accelerate an immune response towards the therapeutic product, which has impact on efficacy and patient safety. We developed a platform for the analysis of insulin aggregates with selected characteristics. We connected size, structure, and chemical modifications of the aggregates to their immunogenicity potential in vitro and in vivo. The results show that micron-sized aggregates with highly altered structure were the most immunogenic species.

What do we know so far about the in-use handling of protein drugs? Which are the steps and the stressors involved in the handling between release from the manufacturer to their administration and use? And who are the people involved? These are questions that are addressed in this literature survey.

Molecular protein-protein interaction (PPI) mechanisms in high-concentrated protein systems are of fundamental importance for the rational development of monoclonal antibody (mAb) formulations. A direct extrapolation of physicochemical properties obtained from measurements at a low protein concentration of the corresponding properties at a high protein concentration is highly questionable. Here, protein hydration, protein dipole moment, and protein-protein interactions were studied in protein concentrations up to 1.3 mM using dielectric relaxation spectroscopy.

Retinal diseases, both inherited and acquired, lie at the root of severe vision impairment which affects millions of patients worldwide. While industry and academia are exploring a plethora of cell and gene therapy products, several ocular drug delivery barriers hinder their effective delivery to the retina. Smart design of nanoparticles and/or controlled modulation of the barriers involved could therefore offer a significant therapeutic benefit. Applying advanced ex vivo models, our research group, therefore, investigates retinal delivery in function of nanoparticle characteristics. At the same time, we look into innovative ways to manipulate ocular barriers making use of photoporation.

Traditional particle monitoring processes consume the majority of all sample volume during stability studies. An optimization of processes and workflow may allow preserve more than 90% of the sample volume or in turn allows 10 times more insights during early pharmaceutical development. I will present a case study that shows – if we are up to slightly change our processes – we can truly bring formulation development to another level.