The global burden of dengue is rising rapidly, creating an urgent and growing unmet medical need. Hundreds of millions of dengue infections are estimated to occur worldwide each year according to the WHO, although reported cases capture only part of the burden. Climate-driven expansion of mosquito vectors is accelerating the spread of dengue into previously unaffected regions, increasing both healthcare and economic costs. However, there are currently no approved specific antiviral therapies for the treatment or prevention of dengue infection, highlighting a significant opportunity for therapeutic innovation.

Laying the Scientific & Translational Foundations

In 2010, scientists at the KU Leuven Rega Institute and CD3 were awarded a Wellcome Trust Seeding Drug Discovery Initiative grant, combining Rega’s world-leading expertise in virology with CD3’s drug discovery capabilities. The collaboration focused on identifying and optimising novel compounds targeting the dengue virus replication machinery. Together, the teams discovered first-in-class NS4B inhibitors with potent activity against all four dengue virus serotypes and favorable ADMET properties. This scientific and translational progress proved instrumental in securing a collaboration with Janssen Pharmaceuticals (Johnson & Johnson) in 2013, paving the way for further development of these promising antiviral candidates.

From discovery to clinical evidence

Building on the foundation established by Rega and CD3, Johnson & Johnson advanced the program through lead optimisation, clinical candidate selection and clinical studies.

In a Phase 2a controlled human infection study (Durbin et al., The New England Journal of Medicine, 2025), treatment with mosnodenvir significantly reduced the number of infected individuals and lowered dengue virus levels in those who were infected, compared with placebo-treated participants. New clinical findings reported by Professor Anna Durbin (Johns Hopkins Bloomberg School of Public Health) and colleagues confirm the dose-dependent antiviral activity of daily mosnodenvir and extend these findings to once-weekly dosing (Van Wesenbeeck et al., The New England Journal of Medicine, 2026). More than 900 people have received mosnodenvir in clinical studies to date, with no safety concerns identified.
The rights to mosnodenvir have recently reverted to KU Leuven. CD3 and KU Leuven are now seeking a partner with the expertise and capacity to take its development forward.

Global Impact Potential

As dengue continues to spread globally, causing millions of infections each year, the need for effective therapeutic options has never been greater. A safe, orally available, first-in-class antiviral could become an important addition to existing prevention strategies, complementing vaccination and vector-control measures.

This programme illustrates the power of long-term collaboration between academia, translational research organizations, and industry. From an initial discovery grant to a clinical-stage antiviral candidate, it demonstrates how scientific excellence and drug discovery expertise can be combined to address urgent global health challenges and bring innovative therapies closer to patients.