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).