Johan Luthman, EVP and Head of Research & Development at Lundbeck A/S, spoke ahead of Biomarkers, CDx & Precision Medicine EU 2026 about the transformation of Lundbeck's research strategy, the evolving role of biomarkers in neuroscience, and what it will take to turn biological insights into medicines that genuinely benefit patients.
Describe your role and the transformational activities you have conducted at Lundbeck.
Luthman has led Lundbeck's R&D organisation for more than seven and a half years, overseeing a fundamental shift in strategic direction. While Lundbeck remains deeply committed to psychiatry, the company has broadened its focus to include neurology, rare diseases, and neuroendocrinology—areas where the science is grounded in measurable biology and where precision medicine approaches are increasingly viable.
Rebuilding the portfolio around new asset types and expanding the company's drug modality platforms has been central to this transformation.
Where are biomarkers creating the most practical impact today: target selection, patient stratification, endpoint sensitivity, or earlier go/no-go decisions?
Luthman described an ideal scenario in which biomarkers travel with a programme from the earliest cell-based assays all the way through to primary and secondary clinical endpoints.
He noted that in fields such as neuroendocrinology, this continuity is genuinely achievable, whereas in other indications the path is far less predictable.
He identified early development as the area of greatest practical impact, specifically the ability to de-risk decisions through outcome biomarkers and to ensure that mechanistic readouts are being tested in the appropriate patient populations through diagnostic and precision medicine biomarkers.
In CNS disorders, what does a "useful" biomarker need to prove before you trust it in clinical development?
Luthman outlined a layered framework for evaluating biomarker utility.
He distinguished between:
• Target engagement or occupancy biomarkers, which confirm the drug is reaching the correct biological compartment.
• Pharmacodynamic or proof-of-mechanism biomarkers, which demonstrate that the biology is being shifted in the intended direction and help establish dose-response relationships.
• Proof-of-principle biomarkers, which connect drug activity to the core disease pathophysiology through measures such as PET imaging, fluid biomarkers, or other biological indicators.
True proof of concept, he argued, emerges only when all these layers are integrated with meaningful clinical readouts. This complete package is what ultimately justifies major Phase III investment.
How should the field avoid over-promising on biomarkers, especially when biology is complex and patient populations are heterogeneous?
Luthman identified validation as one of the most underestimated challenges in biomarker development.
Some biomarkers currently used in clinical practice have required fifteen to twenty years of exploratory work before their relevance was fully established.
He warned against two common pitfalls:
• Over-interpreting promising signals from small, early-stage studies.
• Mining large datasets until favourable findings emerge and then retrospectively treating them as predictive.
Luthman emphasised the importance of rigour and objectivity throughout the development process, noting that enthusiasm for new biology can sometimes lead organisations to oversell biomarker potential before sufficient evidence exists.
How do biomarkers help bridge the gap between exciting neurobiology and a developable therapeutic?
Luthman described the current period in neuroscience as genuinely historic.
Researchers now have access to an increasingly sophisticated toolkit that includes:
• Cerebrospinal fluid biomarkers
• Blood-based biomarkers
• Structural MRI
• Functional MRI
• PET imaging
• Electrophysiological measures
These technologies are becoming increasingly capable of capturing disease biology at the molecular level and translating those insights across the drug development continuum.
He observed that neuroscience is approximately ten to fifteen years behind oncology in its adoption of precision medicine approaches. However, progress in several neurological indications is accelerating rapidly. Biomarker-defined diagnosis of Alzheimer's disease, for example, represents a development that would have seemed unlikely only a decade ago.
How are biomarkers changing Phase 2 trial design in neuroscience?
Luthman acknowledged that neuroscience has experienced a series of high-profile late-stage development failures, requiring a reassessment of trial design strategies.
He advocated for a reinvention of Phase 2 studies that moves beyond simple proof of efficacy and instead focuses on:
• Establishing the optimal dose
• Understanding mechanism of action
• Confirming biological activity in the intended patient population
He highlighted adaptive trial designs, Bayesian statistical approaches, and early Phase 1b patient studies as valuable tools for generating stronger evidence before progressing to large-scale pivotal programmes.
What have recent failures in neuropsychiatry and neurology taught the industry about biomarker strategy?
According to Luthman, the most important lesson is patience.
Many unsuccessful programmes have progressed too quickly from Phase 1 to Phase 3 without sufficiently characterising drug behaviour in patients during earlier development stages.
While small studies can produce misleading signals, he argued that the solution is not to bypass them. Instead, developers should interpret early data carefully and use it to build a robust evidence package before committing to major investments.
What would you like regulators, clinicians, and industry to align on to accelerate biomarker-enabled drug development?
Luthman expressed a generally positive view of his interactions with regulatory agencies, describing them as partners in development rather than obstacles.
He recommended early and ongoing engagement with regulators, encouraging companies to involve agencies throughout the development process rather than presenting conclusions only at the end.
On the academic side, he highlighted the importance of:
• Pre-competitive research consortia
• Large natural history studies
• Shared evidence-generation initiatives
He cited the Alzheimer's Disease Neuroimaging Initiative (ADNI) as an exemplary model. The programme has tracked imaging, fluid biomarkers, genetics, and clinical outcomes across large patient populations over decades, creating a valuable evidence base for biomarker development.
Looking five years ahead, what would success look like for biomarkers in brain health?
Luthman envisions a future in which precision medicine is broadly integrated throughout neurology, with biomarker-defined disease subgroups becoming the standard framework for therapeutic development.
He predicts that today's broad diagnostic categories will increasingly be subdivided into:
• Specific pathophysiological subtypes
• Distinct disease stages
• Clearly defined patient populations
This increased biological resolution should enable more targeted and effective treatments.
He also highlighted the transformative potential of digital and AI-driven technologies in psychiatry. Today, psychiatric diagnosis remains largely dependent on subjective patient-reported symptoms. Objective digital measures of behaviour and function could fundamentally change this paradigm, helping transform psychiatry from one of medicine's most subjective disciplines into one grounded more firmly in biological science.
KEY TAKEAWAYS
• Biomarkers create the greatest immediate value during early development by improving decision-making and reducing programme risk.
• Successful biomarkers require extensive validation and should be evaluated through a layered framework encompassing target engagement, mechanism, and proof of principle.
• Neuroscience is entering a period of accelerated biomarker innovation, supported by advances in imaging, fluid biomarkers, and precision medicine technologies.
• Future Phase 2 studies will increasingly focus on understanding mechanism and dose optimisation rather than efficacy alone.
• Precision medicine approaches are expected to redefine neurological diseases into biologically meaningful subgroups, enabling more effective therapies.
• Digital and AI-based biomarkers may fundamentally reshape psychiatric diagnosis and treatment over the coming decade.
