Currently the Arthrogen lead compound in clinical development is ART-I02, a recombinant adeno-associated virus (rAAV) type 5 vector genetically designed to encode human interferon-β (hIFNβ).

Transcription of the hIFNβ mRNA is controlled by an inflammation-inducible promoter, the nuclear factor (NF)-κB-responsive promoter, resulting in the expression of the therapeutic protein during flares of disease. The type I IFNs, IFNβ and various IFNα’s, are pleiotropic cytokines acting on a range of cell types and eliciting a diverse range of responses.

Based on in vitro work and experiments in animal models of RA, the effects of IFNβ are mainly anti-inflammatory. Furthermore, IFNβ has an important role in maintaining bone homeostasis and has shown to have anti-angiogenic properties, which could boost a therapeutic effect in RA. In proof-of-principle studies Arthrogen has shown that overexpressing of IFNβ locally in the joints using a gene therapy approach ameliorates arthritis in animal models of disease. Interferon-β treatment protected against clinical signs of arthritis, inflammation in the joint, and bone and cartilage erosions.

Together the results provide a strong rational for IFNβ as a therapeutic target for intra-articular gene therapy for arthritis. Currently ART-I02 is in the clinical phase of development and a Phase Ib clinical trial has started in 2017.