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Multiple Sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the CNS (central nervous system) that damages the fatty myelin sheaths around the axons of the brain and spinal cord. This damage, destruction, and loss or scarring of the myelin sheaths (sclerosis or plaques) results in a broad spectrum of symptoms. MS is a chronic, disabling disease that affects ~ 400,000 people in the United States alone and it is estimated that nearly ~2.5 million people worldwide are diagnosed with MS.  MS substantially and adversely affects the quality of life of each individual. The most common symptoms of MS include loss of muscle control and strength, fatigue, weakness, loss of vision, spasticity, balance, sensation, bladder and bowel problems, numbness, vision loss, tremors, and mental function such as depression. In the United States alone MS care is estimated to cost nearly $13 billion per year. Inflammatory cytokines and its receptors have an important role in the progression of MS lesions, and pro‑ and anti‑inflammatory cytokine levels have been found to correlate with changes in MS disease activity. Currently available treatments usually focuses on strategies to treat MS attacks (Corticosteroids), manage symptoms and reduce the progress of the disease. It includes; Avonex, Betaseron, Rebif, Tysabri, Mitoxantrone, Ampyra, oral Teriflunomide, Copaxone, and oral Fingolimod but none of these medications is a cure or prevent recurring symptoms. In addition to existing oral DMT drugs such as Fingolimod, Cladribine, and recently approved Tecfidera and ~ 46 other experimental agents in various stages of clinical development such as Laquinimode, and Masitinib have been reported to cause serious adverse events including opportunistic infections, antibody stimulation, and liver and kidney toxicities. Target specific inhibitors or antagonists should promote myelination, neuronal repair, halting neurodegeneration, and should eliminate many of these adverse events.
Arrien Pharmaceutical has discovered and advanced the development of small molecule antagonists targeting Retinoic acid-related orphan nuclear receptor gt (RORgt)/RORg. RORgt is the key transcription factor and is the master regulator of human Th17 (T helper 17) cells, a unique subset of CD4+T cells. RORgt controls cellular differentiation, function and InterleukinIL-17 (IL-17 producing T-helper lymphocytes) release by Th17 cells and helps mediate the immunopathology of human autoimmune diseases such as Multiple Sclerosis (MS), Rheumatoid Arthritis (RA), Inflammatory Colitis, Psoriasis, COPD, and Asthma.

Using proprietary, Fragment-Field Drug Design (FFDD) based technology and uniquely designed specific RORgt isoform assays, Arrien Pharmaceutical has discovered ARN-6039, a novel, potent, orally available, brain penetrant small molecule and is a specific RORgt antagonist (inverse agonist) that demonstrated its RORgt activity in an RORgt-activated IL-17A in IL-17 release from CD4+T cells assays, as well as inhibition of IL-17 production in vivo in BALB/c mouse experiments.
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