Navigating the path to better treatment options with engineered biologics
Autoimmune diseases are notoriously complex. Despite progress in advancing treatment options for many conditions, the choices are still limited for patients living with debilitating diseases. For some, current therapies don’t provide sufficient relief. For others, there are simply no options at all.
At Navigator, we are advancing next-generation biologics that leverage clinically-validated mechanisms toward potentially addressing unmet needs of patients.
OX40L: A clinically-validated target with unique potential
OX40 and its ligand OX40L are members of the TNFR and TNF superfamilies that play a critical role in autoimmune diseases. OX40L is expressed on antigen-presenting cells and activated B cells. OX40L signaling co-stimulates immune reactions mediated by T cells. Co-stimulation is essential for an efficient T cell response; without co-stimulatory interactions between membrane bound receptor-ligand pairs, a T cell is rendered ineffective.
As a central regulator sitting upstream of other clinically-validated signaling pathways in inflammation, the OX40-OX40L axis is an ideal target as a monotherapy and for combination approaches aimed at potentially improving and broadening benefit for patients.
NAV-240
A tetravalent bispecific antibody targeting OX40L and TNFα
NAV-240 is a clinical-stage bispecific antibody designed to downregulate inflammation by blocking both TNFα and OX40L-induced signaling. Anti-TNFα antibodies, which target type 1 inflammation, are treatment options for many, but not all, patients with a range of autoimmune conditions.
NAV-240 acts through dual modification of inflammatory cytokines and adaptive immune responses to potentially modulate long-term immune homeostasis by acting on both type 2 and non-type 2 driven inflammation. Pairing OX40L with TNFα has biological and clinical rationale to potentially address unmet needs in complex, heterogenous autoimmune diseases, including hidradenitis suppurativa, inflammatory bowel disease, rheumatoid arthritis, and systemic sclerosis.
Downregulation of type 2 and non-type 2 inflammation via rationally designed biologics
OX40L expression across Th1, Treg, Tfh, Th17, and Th2 cells make it an ideal target to combine for the development of multi-specific molecules.
Navigator Medicines at 2025 AAD Annual Conference
A First-in-Human Phase 1a Randomized, Double-Blind, Single-Ascending Dose Study of NAV-240,
an anti-OX40L/TNFα Bispecific Antibody, in Healthy Volunteers
