The global burden of dengue is rising rapidly, creating an urgent and growing unmet medical need. More than 7.6 million cases were reported to the WHO by the end of April 2024, although the true number of infections is believed to be considerably higher. 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 optimizing 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.

Accelerating with Johnson & Johnson

Building on the foundation established by Rega and CD3, Johnson & Johnson advanced the program through lead optimization and clinical candidate selection, ultimately progressing the candidate into multiple Phase 1 clinical trials.

The collaboration also resulted into two additional Open & Operating (O&O) grants for the consortium, further supporting continued innovation in the field of dengue antivirals.

In 2023, Johnson & Johnson reported promising results for JNJ-1802 (Mosnodenvir) in a randomized Phase 2a dengue human challenge study, demonstrating antiviral activity alongside a favorable safety and tolerability profile. The compound has since advanced into larger multi-country field studies designed to establish efficacy under real-world conditions, while the broader program pursues Phase 2 clinical development.

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 program 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.