Mannan-binding lectin-associated serine protease-2, or MASP-2, is a novel pro-inflammatory protein target involved in activation of the complement system, which is an important component of the immune system. The complement system plays a role in the inflammatory response and becomes activated as a result of tissue damage or microbial infection. Inappropriate or uncontrolled activation of the complement system can cause diseases characterized by serious tissue injury. MASP-2 is recognized as the effector enzyme, and is required for the function, of the lectin pathway, one of the principal complement activation pathways. Importantly, inhibition of MASP-2 does not appear to interfere with the antibody-dependent classical complement activation pathway, which is a critical component of the acquired immune response to infection. We are developing MASP-2 antibodies and small molecules and we expect that the intended therapeutic effect can be achieved through multiple routes of administration, including subcutaneous and intravenous administration of our antibodies and oral and intravenous administration of our small molecules.
OMS721, our lead fully human monoclonal antibody targeting MASP-2, is being developed for diseases in which the lectin pathway has been shown to contribute to significant tissue injury and pathology. These diseases are typically characterized by significant end organ injuries, such as kidney or central nervous system injury, when not treated. One group of such diseases is thrombotic microangiopathies (TMAs), including atypical hemolytic uremic syndrome (aHUS), and hematopoietic stem-cell transplant-related, or HST, -related TMA. Another group are complement-associated renal diseases, such as Immunoglobulin A (IgA) nephropathy.
OMS721 has received from the FDA: (1) orphan drug designation for the prevention (inhibition) of complement-mediated TMAs and for IgA nephropathy; (2) fast track designation for the treatment of patients with aHUS; (3) breakthrough therapy designation for the treatment of IgA nephropathy; and (4) orphan drug designation in IgA nephropathy. In addition, OMS721 has received from the EMA orphan drug designation in patients with IgA nephropathy.
Phase 3 clinical programs are in process for OMS721 in IgA nephropathy, in HCT-TMA, and in aHUS. We also have ongoing Phase 2 clinical trials in patients with HCT-TMA and in patients with renal disease (including IgA nephropathy) Patient enrollment is underway for the Phase 3 trial in patients with IgA nephropathy and the Phase 3 trial in patients with aHUS. We have initiated a Phase 3 program for OMS721 in HCT-TMA, and intend to amend the ongoing Phase 2 HCT-TMA trial protocol following discussion with the FDA and/or the EMA regarding accelerated and/or conditional approval.
We hold worldwide exclusive licenses to rights related to MASP-2, antibodies targeting MASP-2 and the therapeutic applications for those antibodies from the University of Leicester, Medical Research Council at Oxford University, and from Helion Biotech ApS. As of February 16, 2018, we exclusively controlled 19 issued patents and 29 pending patent applications in the U.S., and 273 issued patents and 101 pending patent applications in foreign markets, related to our MASP-2 program.
As part of our MASP program, we have identified mannan-binding lectin-associated serine protease-3, or MASP-3, as what we believe is the key activator of the alternative pathway of the complement system, and we believe that we are the first to make this and related discoveries associated with the alternative pathway. The complement system is part of the immune system's innate immune response, and the alternative pathway is considered the amplification loop within the complement system. Based on our alternative pathway-related discoveries, we have expanded our intellectual property position to protect our inventions stemming from these discoveries beyond MASP-2-associated inhibition of the lectin pathway to include inhibition of the alternative pathway. In addition to our MASP-2 inhibitors of the lectin pathway, we are developing inhibitors of the alternative pathway as well as bispecific inhibitors of both the alternative and lectin pathways. For each of these targets, our efforts are directed to both antibody and small-molecule development. We believe that MASP-3 inhibitors may have the potential to treat subjects suffering from a wide range of diseases and conditions, including: paroxysmal nocturnal hemoglobinuria (PNH); C3 glomerulopathy; multiple sclerosis; arthritis; traumatic brain injury; neuromyelitis optica; pauci-immune necrotizing crescentic glomerulonephritis; disseminated intravascular coagulation; age-related macular degeneration; asthma; dense deposit disease; Bechet’s disease; aspiration pneumonia; TMA; ischemia-reperfusion injury; Guillain Barre syndrome; Alzheimer’s disease; amylotrophic lateral sclerosis; systemic lupus erythematosus; diabetic retinopathy; uveitis; chronic obstructive pulmonary disease; transplant rejection; acute respiratory distress syndrome; antineutrophil cytoplasmic antibody-associated vasculitis; anti-phospholipid syndrome; atherosclerosis; myasthenia gravis and others.
In preparation for clinical trials, the manufacturing scale-up process is underway for a MASP-3 inhibitor antibody and we are currently targeting PNH as the first clinical indication for OMS906. We also are developing small-molecule inhibitors of MASP-3.
We own and exclusively control under a license from the University of Leicester all rights to methods of treating various disorders and diseases by inhibiting MASP-3. As of February 16, 2018, we exclusively controlled four pending patent applications in the U.S. and three issued patents and 43 pending patent applications in foreign markets that are directed to these therapeutic methods.