Lundbeck is a unique company with a strong focus on neuroscience. It is primarily owned by a foundation, which offers Lundbeck stability in the strategy they are developing, as well as the possibility of refunds and reinvestments back into basic research. Morten Grunnet, Vice President & Head of Neuroscience at Lundbeck, outlined his research efforts into biological clusters and neuroimmunology.
Like many companies, there is a major focus on target selection, which involves choosing a feasible modality, understanding the biological rationale and mode of action, checking biomarker availability, and conducting pre-clinical pathophysiological modelling. Grunnet added that there has been a shift in interest from small molecules to antibodies, but characterised Lundbeck as a modality-agnostic company.
It is well documented that CNS discovery is fraught with translational challenges. There is a significant translational gap between animal models and human CNS disorders, especially in psychiatric conditions.
Mice brains have around 100 – 200 million neurons, whereas human brains have about 100 billion, so there is a large discrepancy in behaviours and limitations regarding how well mouse models can recapitulate human physiology. Luckily, Lundbeck is addressing this by focusing on underlying biological and biochemical mechanisms rather than direct behavioural translation.
Grunnet expressed that it is vital to recognise the importance of choosing animal models with strong translational validity. For instance, some models, like epilepsy and Dravet syndrome, are more predictive than models for psychiatric conditions like depression. Even gender differences in animal models are also taken into account, particularly in migraine research.
Switching gears, early integration of pharmacokinetics (PK) and pharmacodynamics (PD) is used to optimise and prioritise compounds. Lundbeck adopts a holistic outlook by using multiple assays and models to assess therapeutic index and predict human dosing. Yet Grunnet also acknowledged the shortcomings in accurately predicting human PK.
In a nutshell, Lundbeck always seeks to de-risk early in development and focus on biological understanding and biomarker translation to ensure that high-quality candidates progress to clinical phases. Adopting the fail-fast, fail-early method is needed to avoid costly late-stage failures.
