SLG-100 - A Clinical Stage Therapeutic Product For Treating Dry Eye Disease (DED)
In the USA 17 million patients have been diagnosed with Dry Eye Disease (DED). As many as 5 - 35% of patients visiting an ophthalmology clinic report DED symptoms, making DED one of the most common conditions seen by ophthalmology specialists. The global DED market was estimated at 4.5 billion USD in 2020, covering prescription drugs, OTC drugs and medical devices. DED is the 3rd largest indication of the overall ophthalmology market. The largest segment of the DED market are artificial tears, which comprise more than 50% market share with estimated 2.6 billion USD. Therefore, there exists an unmet need for effective prescription therapeutics for DED.
Current therapeutic strategies for 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 direct actions against DED-specific inflammatory proteins (cytokines) or pathogenic autoantibodies.
SLG-100 eye drops shift the current paradigm of DED treatment that focuses on T-cell mediated inflammation as central to the pathophysiology to also include direct neutralizing actions against DED-specific inflammatory proteins (cytokines) and 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 anti-cytokine antibodies and anti-idiotypic (anti-immunoglobulin) antibodies with specific actions against DED-specific cytokines and 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.