Date: 2014-12-22
Type of information: Licensing agreement
Compound: foralumab (NI-0401)
Company: Novimmune (Switzerland) Tiziana Life Sciences (UK)
Therapeutic area: Autoimmmune diseases - Digestive diseases - Inflammatory diseases - Transplantation
Type agreement: licensing
Action mechanism: monoclonal antibody. Foralumab (NI-0401) is a monoclonal antibody targeting CD3-epsilon. It s intended to alter auto-aggressive T-cell responses by targeting the T-cell receptor complex. CD3-epsilon (or CD3?) is a molecule that sits on the surface of T-lymphocyte. In humans, CD3-epsilon is encoded by the CD3E gene on Chromosome 11. The CD3? molecule, along with four other membrane-bound polypeptides (CD3-gamma, -delta, -zeta, and -eta) form the CD3 complex. The CD3 complex, in turn, is associated with the T-cell receptor (TCR), which consists of additional molecules also on the surface of the T-cell, whose job is to recognize and combine with antigens. When an antigen binds to the T-cell receptor, the CD3 complex sends signals through the cell membrane to the cytoplasm inside the T-cell. This causes activation of the T-cell that rapidly divide to produce new T-cells sensitized to fight the particular antigen to which the TCR were exposed. While T-cell activation is critical for the human immune system to properly fight bacterial, viral or parasitic infections, abnormal T-cell induction can cause and worsen numerous human diseases, including T-cell lymphoma and leukemia, human malignancies, autoimmune disorders, cardiovascular disease, and transplant rejection. A Phase I and Phase IIa clinical trial in Crohn's disease, and a Phase I?/?II open-label study in renal allograft transplantation have been completed.
Disease:
Details: * On December 22, 2014, Tiziana Life Sciences, a clinical stage biotechnology company focused on targeted, drugs to treat diseases in oncology and immunology, and Novimmune, a company focused on the discovery and development of antibody-based drugs to benefit patients with inflammatory, auto-immune disorders, and cancer, announced that they have entered into an agreement under which Novimmune grants Tiziana an exclusive license for the clinical development and commercialisation of foralumab, a fully human antihuman CD3 receptor monoclonal antibody (CD3 mAb). Foralumab is a phase II asset with potential application in a wide range of autoimmune and inflammatory diseases, such as multiple sclerosis, type-1 diabetes (T1D), inflammatory bowel disease (IBD), psoriasis and rheumatoid arthritis, where modulation of a T-cell response is desirable. Evidence suggests that in rheumatoid arthritis, anti CD3 antibodies, when used in conjunction with anti-TNF antibodies such as Humira®, Remicade® and Enbrel® – which represent a multi-billion dollar market – may exhibit a synergistic effect. In the coming months, Tiziana will be evaluating and prioritising such potential therapeutic applications of foralumab. Tiziana will continue to focus strongly in the field of oncology, advancing its pre-clinical breast cancer research programmes in Bcl-3 and “Top 20”, and now has a clinical stage asset to complement its pre-clinical portfolio.
Financial terms: Tiziana will pay an upfront fee of $1.25 million for the license to Novimmune within 60 days after signing the agreement and will make further payments to Novimmune totalling $750,000 by February 2018. Tiziana will also pay a royalty on sales or a share of sub-licence revenues to Novimmune, subject to the deduction of certain costs.
Latest news: * On May 19, 2016, Tiziana Life Sciences announced that foralumab, was featured in a review article entitled, “Therapeutic anti-CD3 monoclonal antibodies: from bench to bedside” published online ahead of print in Immunotherapy (see http://www.futuremedicine.com/toc/imt/0/0). This follows the announcement made on 11 January 2016 that outlined Tiziana’s plans to initially evaluate foralumab in two clinical indications; namely, graft vs host disease, and ulcerative colitis, an inflammatory bowel disease. The review article, authored by Dr. Howard Weiner, who joined Tiziana’s Scientific Advisory Board earlier this year, and Dr. Chantal Kuhn of Harvard Medical School, highlights unique attributes of foralumab that differentiate it from the other anti-CD3 monoclonal antibodies (mAbs) evaluated in the past. In particular, it was noted that foralumab is currently the only fully human anti-CD3 mAb in development and that this should potentially translate into reduced side effects and improve the overall safety profile of foralumab compared to other anti-CD3 mAbs in development, potentially translating to reduce side effects and an improved overall safety profile as compared with murine and other non – human mAbs. * On January 11, 2016, Tiziana Life Sciences announced its plan for further development of foralumab. The company will first be evaluating foralumab in two clinical indications, graft vs host disease and ulcerative colitis.
