New Jersey-based biotech Navigator Medicines is advancing two bispecific antibodies targeting OX40L and TNFα into clinical development, marking a significant progression in the company’s strategy to address complex inflammatory disorders. The company’s lead candidates, NAV-240 and NAV-242, are designed to simultaneously inhibit two inflammatory pathways in hidradenitis suppurativa (HS), a chronic and painful skin condition.

The U.S. Food and Drug Administration has cleared an Investigational New Drug (IND) application for NAV-240’s Phase 2a trial in HS, while the company has also received Australian ethics committee approval to initiate a first-in-human Phase 1 study for NAV-242, a next-generation half-life-extended bispecific antibody.

About NAV-240 and NAV-242

The dual targeting of OX40L and TNFα represents a novel approach to managing inflammatory diseases. Current literature, including a recent AllSci-indexed publication “Combined TNFα and OX40L targeting as a new treatment option for Hidradenitis suppurativa”, suggests that simultaneous blockade of these pathways could provide superior inflammatory suppression compared to existing monotherapies.

NAV-240’s Phase 2a trial will evaluate the therapy in moderate-to-severe HS patients, building on previous Phase 1 safety data. The companion molecule, NAV-242, is engineered for extended half-life and will undergo a Phase 1 single ascending dose study in healthy volunteers and HS patients, with initial results expected in late 2026.

Navigator acquired rights to NAV-240 (previously IMB101) in global markets outside of Asia via a licensing deal with South Korea’s IMBiologics in 2024, and recently expanded the rights to include Greater China.

Competitive Landscape

Hidradenitis suppurativa affects approximately 1% of the global population, with over one million people in the U.S. experiencing moderate-to-severe disease. While Navigator Medicines is pioneering this dual-target approach, the HS therapeutic space is evolving. After nearly a decade with only one approved biologic (Humira), the FDA has recently approved several new therapies, and a robust pipeline of oral and targeted drugs is nearing the finish line.

Recent FDA approvals include UCB’s Bimzelx (bimekizumab), an IL-17A & IL-17F inhibitor approved in November 2024, and Novartis’s Cosentyx (secukinumab), an IL-17A inhibitor approved in October 2023. Prominent pipeline candidates for HS include JAK inhibitors (povorcitinib, ruxolitinib, and others), IL-1/IL-36 inhibitors, BTK inhibitors (remibrutinib), and IRAK4 degraders (KT-474), with multiple sponsors pursuing first-in-class or best-in-class strategies, with MoonLake Immunotherapeutics, Novartis, Incyte, InflaRx, and others at the forefront.