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 is believed to contribute to significant tissue injury and pathology. One group of such diseases is thrombotic microangiopathies (TMAs), including atypical hemolytic uremic syndrome (aHUS), thrombic thrombocytopenic purpura (TTP) and hematopoietic stem-cell transplant (HSCT)-related TMA. These diseases are typically characterized by significant kidney or central nervous system injury when not treated.
OMS721 has received orphan drug designation from the FDA for the prevention (inhibition) of complement-mediated TMAs and fast track designation from the FDA for the treatment of aHUS. We have requested from the FDA fast track designation and orphan drug designation for OMS721 in immunoglobulin A (IgA) nephropathy (also known as Berger's disease). We plan to pursue breakthrough therapy designation for OMS721 in IgA nephropathy and HSCT-related TMA and accelerated approval for OMS721 in both of those indications as well as in aHUS.
A Phase 3 program for OMS721 in aHUS is in progress. Two Phase 2 trials are ongoing. One is evaluating OMS721 in glomerulonephropathies, which has generated positive data in patients with IgA nephropathy and with membranous nephropathy and, in a patient with C3 glomerulopathy, findings from kidney biopsies demonstrate substantial improvement following treatment with OMS721. The other Phase 2 trial is being conducted in patients with TMAs, with positive data reported in patients with HSCT-related TMA. In addition to potential intravenous administration, Omeros plans to commercialize OMS721 for one or more therapeutic indications as a subcutaneous injection and is also developing small-molecule inhibitors of MASP-2. Based on requests from treating physicians, Omeros has established a compassionate-use program for OMS721, which is active in both the U.S. and Europe.
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 March 8, 2016, we exclusively controlled 13 issued patents and 22 pending patent applications in the U.S., and 61 issued patents and 87 pending patent applications in foreign markets, related to our MASP-2 program and associated complement targets.
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), TMAs, arthritis, dense deposit disease, aspiration pneumonia, pauci-immune necrotizing crescentic glomerulonephritis, traumatic brain injury, disseminated intravascular coagulation, neuromyelitis optica, asthma, Behcet's disease and age-related macular degeneration.
We are currently finalizing selection of our lead and back-up molecules and are initiating the process for scale-up in our OMS906 program in preparation for clinical trials.
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 March 8, 2016, we exclusively controlled two pending patent applications in the U.S. and 33 pending patent applications in foreign markets that are directed to these therapeutic methods.