Since joining Danish neuroscience specialist Lundbeck as its global CEO in 2018, South African Deborah Dunsire has focused on “revitalising and refreshing” the firm’s pipeline, which had seen several failures in the preceding years. In an exclusive recent conversation with PharmaBoardroom, Dunsire explains the strategy she has put in place to ensure fruitful research programs in the notoriously difficult neuroscience field, including why a move into areas for which biomarkers can be established is key for the company’s future.
Lundbeck, which has a history stretching back to 1915, has traditionally focused its research on Alzheimer’s, Parkinson’s, mood disorders, and schizophrenia, but, as Dunsire notes, “our capabilities go way beyond that.” She adds, “We decided that we had to capitalize on Lundbeck’s experience in neuroscience by looking at many different areas in the field, not only a narrow segment… That allowed us to bring in pipeline products through acquisitions that, while not necessarily in those four traditional areas of focus, were still in our neuroscience sweet spot.”
Lundbeck has begun to redirect its research focus into areas where we have a good understanding of the biology and, importantly, biomarkers that can help us understand and de-risk the programs during development
The first such acquisition was Alder BioPharmaceuticals, which brought a new focus on neuropeptides, signalling molecules involved in areas like migraine, cluster headaches, and other specialty pain syndromes. The second was Abide Therapeutics, which brought in a pipeline of drugs that harness the therapeutic potential of the endocannabinoid system; a system that occurs naturally in the brain and is sometimes mimicked with cannabinoids or cannabis, which can be used to address diseases such as epilepsy and spasticity in multiple sclerosis.
The Abide portfolio is notable in that it involves areas for which biomarkers can be established. As Dunsire outlines, “Lundbeck has begun to redirect its research focus into areas where we have a good understanding of the biology and, importantly, biomarkers that can help us understand and de-risk the programs during development. Lundbeck had never really had activities in areas with a lot of biomarkers, so this is another new capability being introduced within our internal drug discovery and development.”
The benefits of such programs are myriad. “Having biomarkers will accelerate the decision making around whether a drug can go all the way or not; both in terms of moving it forward more quickly or deciding to stop it earlier, thereby freeing up resources to work on more promising areas,” notes Dunsire.
“Additionally, biomarkers can be used to make clinical trials smaller as they allow researchers to see a bigger effect size. More precisely designed clinical trials using biomarkers become smaller, quicker, and less expensive and decisions to either stop or accelerate a program can be made more swiftly. Working in this way comes with several different benefits in terms of de-risking and speeding up the pipeline.”
The use of biomarkers as a pathway to approval also attracts more investment because you can move ahead of waiting for very long-term outcomes
She adds, “I spent a lot of my career in oncology, where the benefit of biomarkers is very apparent; if a patient has a specific mutation in their lung cancer, it predicts that they will respond to an agent that addresses the protein produced by that mutation… The use of biomarkers as a pathway to approval also attracts more investment because you can move ahead of waiting for very long-term outcomes.”
Having historically been a small-molecule-focused company, this expanded portfolio also represents Lundbeck’s first foray into the biologics space. Dunsire is however sanguine that the high investment costs that this field necessitates are balanced by biologics’ potential effectiveness in the long-term, stating that, “Because the biologics are protein molecules/antibodies with a specific target, they tend to have more predictable biomarkers whereby their effects can be seen more clearly and have fewer off-target toxicities. Small molecules can affect receptors other than the target which must be considered in their development. However, biologics tend to affect only one receptor because that is what they are designed to do, creating a potentially clearer path from a safety perspective.”
She adds, “Biologics are more expensive at the early stages of development because their scale up requires cellular systems and is not as easy as the chemical process with which our small molecules are made. Even at scale they carry a higher cost of goods, but there are returns to be made based on having quicker drug development and more certainty on the target.”
Because the biologics are protein molecules/antibodies with a specific target, they tend to have more predictable biomarkers whereby their effects can be seen more clearly and have fewer off-target toxicities
With increased global awareness of mental health issues post-pandemic, a strengthened portfolio, and increased expenditure on focused R&D programs, Dunsire is confident that Lundbeck is well set up for the future, despite the loss of exclusivity for its hypotension in Parkinson’s disease product. Internally, she outlines that “our attention will be focused on our newly launched product in migraine as well as our other big strategic brands in depression and schizophrenia and keep that growth going. We are also moving our pipeline forward with new compounds coming into Phase I and plans to forward some into Phase II.”
In terms of external growth, Dunsire highlights that “Lundbeck has been built over many years through a mix of internally discovered compounds and external partnerships, licensed products, and acquired products. We are going to keep that focus going forward, continuing to advance our own pipeline but always with an eye for promising external opportunities.”