OSE Immunotherapeutics and Nantes University Hospital Announce Initiation of a Phase 1/2 Clinical Trial to Evaluate CD28 Antagonist FR104 in Patients Undergoing Renal Transplantation - Seite 2

Pr. Gilles Blancho, Head of the ITUN, added: “Despite continuous progress in immunosuppressive treatments, the need for medical advances for renal transplant recipients remains very strong. Through FR104, we are hoping to develop an innovative and promising immunotherapy. The key issue in organ transplant is having available efficient immunosuppressive treatments with minimal side effects, thus preserving patients’ quality of life. Moreover, the clinical collaboration between ITUN and OSE fits into Nantes hospital’s commitment to foster partnerships with the pharmaceutical industry in order to help our clinicians participate in clinical trials while simultaneously enabling our patients to benefit from the latest therapeutic advancements.”

FR104 is a monoclonal antibody and an antagonist of CD28. This pegylated monovalent antibody selectively inhibits the CD28 receptor and has potential clinical applications in autoimmune diseases and transplantation.

Due to its selective immunosuppressive activity directed at effector T cells, OSE plans to investigate FR104 for use in kidney transplantation.  Selective CD28 blockage by FR104 might represent an effective immunomodulation strategy by reducing the activation of T lymphocytes, while sparing the activity of regulatory T lymphocytes.

Several studies conducted with FR104 in preclinical models of transplant and other immune-mediated diseases have generated significant immune data demonstrating its ability to promote immunological modulation⁽¹⁾ and ability to reinforce immunosuppression⁽²⁾. In particular, when used as a monotherapy or in combination according to the models, FR104 has shown to efficiently control graft-versus-host disease (GVHD) or renal graft rejection and this control was superior to the one observed with non-selective CD28-antagonist CTLA4-Ig^{(3, 4)}. Additionally, the results from the Phase 1 clinical ⁽⁵⁾ study of FR104 have shown a good clinical and biological safety with an immunosuppressive activity potentially applicable to transplantation and immune-mediated diseases.

(1)	Selective blockade of CD28 on human T cells facilitates regulation of alloimmune responses Masaaki Zaitsu, Fadi Issa, Joanna Hester et al.; JCI Insight. 2017
(2)	FR104, an antagonist anti-CD28 monovalent fab' antibody, prevents alloimmunization and allows calcineurin inhibitor minimization in nonhuman primate renal allograft