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.

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’s Phase 1 clinical study has shown initial signals of efficacy, a good safety profile and the recommended dose for a Phase 2, further supporting the continued clinical development of this asset in autoimmune diseases or in transplantation.

Poirier et al. ; First-in-Human Study in Healthy Subjects with FR104, a Pegylated Monoclonal Antibody Fragment Antagonist of CD28 ; Journal of Immunology; 2016

FR104 is under a global license agreement (April 2021) with Veloxis Pharmaceuticals Inc., a leading transplantation company, to develop, manufacture and commercialize FR104 for all transplant indications. Based on preclinical and Phase 1 successful studies, Veloxis plans to advance FR104 development to provide a new therapeutic option for prophylaxis of organ rejection in patients receiving a solid organ transplant.

A Phase 1/2 trial is evaluating first administration of FR104, in patients undergoing renal transplant. This study is being conducted as part of a collaboration agreement between OSE Immunotherapeutics and the University Hospital of Nantes, the trial’s sponsor.

The purpose of this Phase 1/2 clinical trial is to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of FR104 in renal transplant patients. ( : NCT04837092)

OSE Immunotherapeutics is also planning a new Phase 2 clinical trial with FR104 in autoimmune diseases as the product has showcased a strong development potential in a number of indications.

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