SLG-100 - A Clinical Stage Therapeutic Product

Current therapeutic strategies for Dry Eye Disease (DED) focus on breaking the T-cell perpetuated inflammatory cycle and has led to the development of drugs that target them. There are three FDA approved drugs currently available for treating patients with DED - Cyclosporine 0.05% (Restasis), Cyclosporine 0.09% (Cequa) and lifitegrast 5% (Xiidra). All three FDA approved DED drugs have in common that they affect T-cell function and do not have any actions against pathogenic autoantibodies.

SLG-100 eye drops shift the current paradigm that focuses on T-cell mediated inflammation as central to the pathophysiology of DED to also include autoimmune inflammation that is driven by post-translational modifications in self-proteins (citrullination) and autoantibodies (ACPAs). In contrast to the three FDA approved DED drugs that affect T-cell function, SLG-100 is a biologic comprising pooled human immune globulins that have natural antibodies and anti-idiotypic (anti-immunoglobulin) antibodies with specific actions against autoantibodies, and other anti-inflammatory actions on neutrophils, dendritic cells, T-regulatory cells and complement system. Thus SLG-100 has broad-spectrum anti-inflammatory actions via molecular and cellular mechanisms.

 

SLG-100 is a clinical stage product. We have performed a pilot clinical trial to determine the preliminary therapeutic potential and safety of SLG-100 eye drops in patients with DED. As compared to Vehicle treatment, SLG-100 eye drops twice a day for 8 weeks caused significant reduction in signs and symptoms of DED with no difference in tolerability or adverse events.

Schematic showing mechanisms by way of which SLG-100 eye drops may exert beneficial anti-inflammatory therapeutic effects on the ocular surface.(1): inhibiting neutrophil activation; (2): inhibiting formation of NETs; (3): inhibiting autoantibody (e.g. ACPA) pathogenic actions by directly binding to them (via anti-idiotypic antibodies or natural antibodies); (4) resetting autoantibody-antigen immune complexes threshold for cell activation; (5) inhibiting complement system activation; (6) inhibiting binding of autoantibodies to Fcγ receptors (FcγRs) to reduce ACPA-induced effector signaling due to functional blockade of Fcγ receptors on neutrophils and dendritic cells; and (7): expansion of Regulatory T cell (Treg) population.