Inebilizumab (previously known as MEDI-551) is a humanized mAb that binds to and depletes CD19+ B cells including plasmablasts and plasma cells.

Inebilizumab is currently being tested in a phase 2 study for treating Neuromyelitis Optica Spectrum Disorder (NMOSD). NMOSD is a rare autoimmune disorder in which immune system cells and autoantibodies attack and damage the optic nerves and spinal cord. Clinically, the disease is manifested with attacks/relapses that result in neurological impairment such as blindness, paraplegia, sensory loss, bladder dysfunction, and peripheral pain. The disability from each attack is cumulative, making NMOSD a chronically debilitating and potentially life-threatening disease.

To date, there are no approved therapies for the treatment of NMOSD.

Autoantibodies against aquaporin-4 (and potentially other autoantibodies) in the spinal cord and optic nerve play a key role in the pathogenesis of the disease in most patients. Therefore, depletion of plasmablasts and plasma cells, the cells that produce these and other autoantibodies, can offer a targeted mechanism for the treatment of NMOSD.

Currently, the safety and efficacy of inebilizumab is being evaluated in the N-MOmentum study, the first randomized placebo-controlled trial in patients with NMOSD.

Inebilizumab has been studied in other indications. It has completed the Ph1 in MS and Ph1 Systemic Scleroderma and Ph2 in B cell malignancies.

VIB4920 (previously known as MEDI4920) is a fusion protein designed to bind to CD40 ligand (CD40L) on activated T cells, blocking the interaction with CD40 expressed on B cells and preventing them from differentiating into plasma cells and memory B cells.  Blocking CD40L also inhibits stimulation of T cells by dendritic cells, as well as fibroblasts, inhibiting production of pro-inflammatory mediators.  All these effects combine to produce powerful immunosuppression capable of targeting both T cell and B cell driven diseases.

The first generation of CD40/CD40L antagonist antibodies that were tested clinically caused thromboembolic side-effects, and thus VIB4920 is engineered as a non-antibody structure to omit the Fc region that was responsible for platelet cross-linking.  No cardiovascular safety issues were observed in the two phase 1 studies that have been completed to date: a single-ascending dose study in healthy volunteers, and a multiple-ascending dose study in patients with rheumatoid arthritis.

VIB7734 (previously known as MEDI7734) is a novel treatment for autoimmune and related inflammatory diseases in which the pathology is driven principally by overproduction of type I interferons (IFN-α and β).  VIB7734 targets the plasmacytoid dendritic cells (pDCs), which generate the majority of IFN in pathological states.  VIB7734 binds to a pDC-specific antigen and triggers cell death.  Importantly, pDCs produce not only type I interferons but also type III interferon and other cytokines, which are associated with inflammatory and autoimmune diseases (for example, IL-6 and TNFα).

VIB7734 is currently in a phase 1 single-ascending dose study in patients with any one of 5 autoimmune diseases (SLE, Sjogren’s syndrome, dermatomyositis, polymyositis or scleroderma).

VIB9600 (previously known as MEDI9600) is a humanized effector-deficient anti-FcγRIIA monoclonal antibody that specifically binds to FcγRIIA (CD32A).  FcγRIIA plays a dominant role in antibody-mediated and immune-complex pathology.  By blocking FcγRIIA, VIB9600 is expected to inhibit the downstream effects of myeloid and dendritic cell activation in multiple autoimmune diseases including those currently treated with IVIg therapy, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), RA and SLE.

VIB9600 is a first-in-class opportunity and is ready for Phase 1.  Pharmacology and safety data generated in a 3-month GLP non-human primate study support clinical development.