Navigator Medicines has announced the dosing of first participants in a Phase 1b trial of NAV-240, a clinical-stage bispecific antibody targeting OX40L and TNFα for the treatment of autoimmune diseases. The multiple-ascending dose study in healthy volunteers represents a significant advancement for this dual-targeting therapeutic approach.
Phase 1b Trial Design and Objectives
The Phase 1b study is designed as a multiple-ascending dose trial that will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NAV-240 after repeated administration. The trial is expected to enroll approximately 24 subjects across three dosing cohorts, with interim data anticipated before year-end 2025.
The primary objective focuses on assessing safety and tolerability parameters following repeated dosing, building upon earlier Phase 1a results that demonstrated NAV-240 was safe and well tolerated in healthy volunteers.
Mechanism and Therapeutic Rationale
NAV-240, formerly known as IMB-101, is a bispecific antibody that simultaneously targets OX40L and TNFα, two clinically-validated targets critical in the pathogenesis of several difficult-to-treat inflammatory diseases. According to research presented at ACR Convergence 2023, dual inhibition of TNFα and OX40L axis is associated with reduction of invasiveness in synovial fibroblast and joint destruction in rheumatoid arthritis.
The dual targeting approach may improve upon the efficacy of either monotherapy alone as a potential treatment option for complex, heterogeneous diseases with unmet medical needs. The exposure profile from Phase 1a studies supports once-monthly dosing in patients, which could offer significant convenience advantages.
Clinical Development Progress
Early clinical data from the Phase 1a study demonstrated that treatment with NAV-240 in healthy volunteers was safe and well tolerated. These results collectively support the continued development of NAV-240 in complex autoimmune conditions like hidradenitis suppurativa. Navigator Medicines plans to present this early clinical data at the American Academy of Dermatology (AAD) Annual Meeting in Orlando, Florida, from March 7-11, 2025.
Target Indication: Hidradenitis Suppurativa
Hidradenitis suppurativa (HS) represents a significant market opportunity for NAV-240. This chronic inflammatory skin disease is characterized by painful, recurrent abscesses and lesions, with patients experiencing flare-ups and severe pain that can have a major impact on quality of life.
Prevalence estimates suggest a range of 0.7 to 1.0% in the US, with some estimates as high as 4.0%, affecting three times more females than males. Well over one million people in the US live with moderate-to-severe HS, with only 350,000 currently seeking treatment. The HS market is projected to grow from $2 billion in 2025 to over $10 billion by 2031.
Development Partnership and Licensing
NAV-240's development represents a successful international collaboration. The drug was originally developed by Y-Biologics, IMBiologics, and HK inno.N as IMB-101. In June 2024, these companies licensed the technology to Navigator Medicines for $944.7 million (1.37 trillion won), with the deal including an upfront payment of $20 million and potentially up to $940 million depending on the development process.
The licensing agreement covers all regions globally, excluding Asia but including Japan. Y-Biologics spearheaded the discovery of the OX40L-targeting antibody and the development of the dual-antibody. The technology was also licensed to China's Huadong Medicine for $315.5 million in August 2024, with Huadong's clinical trial application for HDM3019 approved by China's NMPA for rheumatoid arthritis.
Company Leadership and Future Outlook
Navigator Medicines, founded in 2024 as a subsidiary of Sera Medicines through a $100 million Series A financing co-led by RA Capital Management and Forbion, recently strengthened its leadership team with the appointments of Tausif 'Tosh' Butt as Chief Executive Officer and Khurem Farooq as Chairman of the Board of Directors.
According to company leadership, Navigator is "fortunate to have one of the most mature bispecific antibody programs in immunology and inflammation, with NAV-240 recently completing a Phase 1a study and advancing into multi-dose studies later this year."
