Date: 2017-10-19
Type of
information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in the Journal of Immunology
Company: Effimune (France) now OSE Immunotherapeutics (France)
Product: FR104
Action
mechanism:
- monoclonal antibody. FR104 is a new drug candidate, pegylated Fab’ monoclonal antibody fragment inhibitor of CD28, an essential element of the T-cell signaling pathway. CD28 signaling is a critical pathway required for effector T cell expansion and for regulatory T cells inactivation, and FR104 exerts its immunomodulatory function by blocking CD28 signaling and thereby preventing effector T cells but not regulatory T cells function, thereby promoting immune tolerance. Since September 2013, FR104 is developed under a global license agreement with Janssen Biotech.
- Following positive Phase 1 clinical results, OSE Immunotherapeutics announced Janssen Biotech,
exercised its option to further develop FR104. In exchange for this exclusive worldwide license, OSE
Immunotherapeutics is eligible to receive up to €155 million, plus royalties.
Disease: rheumatoid arthritis, psoriasis
Therapeutic
area: Autoimmune diseases – Dermatological diseases - Inflammatory diseases - Rheumatic diseases
Country:
Trial
details:
Latest
news:
- • On October 19, 2017,OSE Immunotherapeutics announced the positive results of two preclinical studies evaluating FR104, an antiantagonist antibody of CD28, a receptor which controls the activity of effector T lymphocytes. The first study, conducted in collaboration with the University of Oxford, was published in the JCI Insight (Journal of
Clinical Investigation) (Selective blockade of CD28 on human T cells facilitates regulation of alloimmune responses
Masaaki Zaitsu,Fadi Issa,Joanna Hester, Bernard Vanhove, and Kathryn J. Wood - JCI Insight. 2017;2(19): e89381).
- This research demonstrated the efficacy of FR104 in a humanized human skin transplant model, which is recognized as representative and predictive of clinical situations. In this model, FR104 significantly prolonged allograft survival compared to an immunosuppressant control product, CTLA4-Ig. The differential advantage provided by the selectivity of
FR104 is to significantly reduce the activation of T lymphocytes, while sparing the activity of regulatory T
lymphocytes. This is a further demonstration of the ability of FR104 to promote immunological tolerance.
- The second study was conducted in collaboration with the Children’s Cancer Research Institute (Washington) and the University of Vienna, and was published in Frontiers in
Immunology (CD28 Blockade Ex Vivo Induces Alloantigen-specific Immune Tolerance but Preserves T-Cell Pathogen Reactivity. Barbara Dillinger, Sarah Ahmadi-Erber, Klara Soukup, Angela Halfmann, Silke Schrom, Bernard Vanhove, Peter Steinberger, Rene Geyeregger, Stephan Ladisch and Alexander Michael Dohnal. Frontiers in Immunology | www.frontiersin.org, doi: 10.3389/fimmu.2017.01152, September 2017 | Volume 8 | Article 1152). This study focused on the control of the graft-versus-host (GVHD) reaction that can follow a bone marrow transplant. The results demonstrated that FR104 blocked the alloreactivity of T-cells, allowing a control of the reaction of the GVHD, without compromising their control of anti-infectious immunity.
- • On November 30, 2015, Effimune announced the publication in leading scientific journals of three different studies confirming the efficacy of FR104 in new preclinical models, and suggesting that it could be a potent new treatment for rheumatoid arthritis and psoriasis. The three studies confirm CD28 as an interesting target and FR104 as a potential tool in immune regulation. They demonstrate the effectiveness of the drug candidate in different preclinical models of autoimmune inflammatory diseases, ywo models of skin inflammation similar to human psoriasis and a model of joint inflammation associated with rheumatoid arthritis.
Psoriasis: The article to be published in the Journal of Immunology shows the role of CD28 in controlling the memory T cell response and demonstrates that selectively blocking CD28 with FR104 also inhibits the long-term response of the memory cells. Blocking this cell type presage a real remission of the disease and not a mere reduction in its appearance. (J Immunol. 2016 Jan 1;196(1):274-83. doi: 10.4049/jimmunol.1501810. Epub 2015 Nov 23. Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates). In the article published in October 2015 in Experimental Dermatology, the authors demonstrate the efficacy of FR104 in a new model of skin inflammation close to human psoriasis (Exp Dermatol. 2015 Oct 29. doi: 10.1111/exd.12891.Selective CD28 antagonist prevents induced skin inflammation in non-human primates). In collaboration with UMR INSERM 1064, a new model for preclinical validation was generated with a topical application of Aldara®, a cream containing 5% Imiquimod. In addition to showing the efficacy of FR104, this new model which is more similar to the human disease can be used to test other therapeutic approaches to psoriasis.
- Rheumatoid Arthritis: The third article, published in November in the Clinical & Experimental Immunology, demonstrates the effectiveness of FR104 in a new collagen-induced pre-clinical model of rheumatoid arthritis (Clin Exp Immunol. 2015 Nov 5. doi: 10.1111/cei.12739). Clinical efficacy of a new CD28-targeting antagonist of T cell co-stimulation in a non-human primate model of collagen-induced arthritis). In collaboration with the primatology center of Rijswijk and the University of Groningen in the Netherlands, the authors conducted a comparative study of the efficacy of FR104 and Orencia® (abatacept), a standard treatment in rheumatoid arthritis. The results show at least equal efficiency of FR104 on symptoms and a better efficiency on disease markers with a different mode of action on immune cells suggesting longer-term effects on the disease.
- A Phase 1 clinical study in humans is now underway since April with FR104.
Is
general: Yes
