Therapeutic hopes arising from preclinical models in transplantation and autoimmune diseases (rheumatoid polyarthritis, psoriasis,…)

In transplantation models performed in vivo (heart3-5, liver6 and kidney,7,8 transplants), CD28 antagonists act in synergy with other products (monoclonal antibodies and calcineurin inhibitors [CNI]). The CNI product class is the treatment of reference, with its leader cyclosporine, often combined with corticoids. Allo-reactivity or graft rejection are inhibited by FR104. Regulatory T cells are induced around and inside the graft and enable compelling graft results on the long term. When associated to calcineurin (without corticoids added, or low dose CNI), FR104 is able to prevent graft rejection, to inhibit the development of alloantibodies and to extend graft survival13 on the long term.

Other models of autoimmune diseases performed in vivo have clearly demonstrated the efficacy of FR104 [encephalomyelitis14, rheumatoid polyarthritis (Vierboom et al, 2016), uveitis10, psoriasis11]. They have confirmed the therapeutic high potential of this anti-CD28 monoclonal antibody.

FR104 has been included in an exclusive global license agreement with Janssen Biotech, Inc., member of Johnson & Johnson, a leading pharmaceutical Group, for indications in autoimmune diseases and transplantation.

FR104, an immunomodulator designed to control regulation of the immune system, has been evaluated in a Phase 1 clinical trial in healthy patients. The positive preclinical results obtained with the FR104, confirming its potential in controlling the immune system, and the partnership with Janssen Biotech Inc., resulted in the transfer of the product to the clinic.

This 10-month, double-blind, randomized clinical trial in 70 healthy volunteers (both men andwomen), aimed at preparing the future development of FR104 in rheumatoid arthritis, and kidney and stem cell transplantation. The primary objective of the trial was to establish the safety of FR104 and to assess its pharmacodynamics and pharmacokinetics.

The positive phase 1 clinical results of this first phase 1 trial with FR104 have shown a good tolerance and an immunosuppressive activity and have been published online* in « The Journal of Immunology » (November 2016). The clinical and biological safety of this new product has shown to be very good in 64 healthy subjects who were administered single or repeated ascending doses of the product. Moreover, the first data of clinical activity arising from this study, challenged with a KLH test, clearly demonstrated an inhibition of the antibody response versus KLH and in a dose-dependent manner.

*First-in-Human Study in Healthy Subjects with FR104, a Pegylated Monoclonal Antibody Fragment Antagonist of CD28
Nicolas Poirier, Gilles Blancho, Maryvonne Hiance, Caroline Mary, Tim Van Assche, Jos Lempoels, Steven Ramael, Weirong Wang, Virginie Thepenier, Cecile Braudeau, Nina Salabert, Regis Josien, Ian Anderson, Ian Gourley, Jean-Paul Soulillou, Didier Coquoz and Bernard Vanhove

References FR104

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  13. Poirier, N. et al, Am. J. Transplant. (2015)
  14. Haanstra, K.G. et al, J.Immunol, 194 (2015)
  15. Vierboom M. et al, Clin Exp Immunol, (2016)
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