The CD28/CTLA-4 pathway controls both T-cell activation and regulatory T-cell down regulation. CD28 receptor is expressed on the surface of the majority of naïve T-cells and is the major co-stimulatory molecule to generate T-cell activation.

In contrast, CTLA-4, a CD28 homologue, is expressed on activated T-cells, especially regulatory T-cells (T-Reg), and has been historically described as the essential component of the regulation of immune self-reactivation. Therefore, the CD28/CTLA-4 pathway is believed to be at the heart of different autoimmune diseases such as rheumatoid arthritis.

FR104, a monoclonal antibody fragment and CD28 antagonist, selectively blunts CD28 co-stimulation while sparing the CTLA-4 co-inhibitory signal. The net effect of CD28 antagonism is down regulating effector T-cells while promoting T-Reg activity.

In a Phase 1 trial performed in 2016, FR104 demonstrated that it was safe, well tolerated and has the potential to show clinical activity in autoimmune diseases, particularly in rheumatoid arthritis (N. Poirier et al.; First-in-Human Study in Healthy Subjects with FR104, a Pegylated Monoclonal Antibody Fragment Antagonist of CD28; Journal of Immunology; 2016).

On November 2, 2018, OSE Immunotherapeutics announced that it will regain the worldwide rights to FR104 previously licensed to Janssen Biotech, Inc., (cf. press release of July 5, 2016) effective December 31, 2018.

Janssen’s decision to return the program FR104 to OSE Immunotherapeutics is based on its own internal strategic review and prioritization of its portfolio.

OSE  is pursuing clinical development of FR104 and is currently evaluating the best options for continuing a sustainable development of the product, including worldwide partnering opportunities.