12 December 2018 - - US-based commercial-stage biopharmaceutical company Omeros Corp. (NASDAQ: OMER) has entered into a research collaboration with the University of Cambridge, establishing the Omeros Center at Cambridge for Complement and Inflammation Research (OC3IR), the company said.

The OC3IR currently is focusing on research related to OMS721, Omeros' lead human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the complement system's lectin pathway, and to OMS906, Omeros' lead human monoclonal antibody targeting MASP-3, the key activator of the complement system's alternative pathway.

OMS721 is currently in three Phase 3 clinical programs stem cell transplant-associated thrombotic microangiopathy, IgA nephropathy and atypical hemolytic uremic syndrome and OMS906 is planned to enter the clinic in early 2020.

Omeros holds proprietary positions around both MASP-2 and MASP-3.

The OC3IR will be led by Professor Wilhelm Schwaeble, DSc, director of Research, working in close collaboration with other Cambridge complement researchers, including Sir Peter Lachmann, ScD FRS FMedSci, Emeritus Sheila Joan Smith Professor of Immunology at the University of Cambridge.

One of the Center's priorities will be to characterize further the role and response of the complement system in endothelial injury, which is implicated in a wide range of diseases including thrombotic microangiopathies, kidney diseases and central nervous system disorders.

The Center will also facilitate collaborative links between Omeros and other leading academic research laboratories in the field of complement and inflammation research.

Any intellectual property resulting from Omeros-sponsored research at the OC3IR will be owned by Omeros, and Omeros will have an exclusive option to acquire all rights to intellectual property that is jointly supported by other funding sources.

Omeros controls the worldwide rights to MASP-2 and all therapeutics targeting MASP-2, 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. MASP-2 is the effector enzyme 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, and its abnormal function is associated with a range of autoimmune disorders.

MASP-2 is generated by the liver and is then released into circulation. Gene-targeted MASP-2-deficient mice and humans with MASP-2 gene polymorphisms that affect MASP-2 serum levels and MASP-2 functional activity are generally healthy with no obvious adverse phenotype.

Phase 3 clinical programmes are in progress for OMS721 in atypical hemolytic uremic syndrome, in immunoglobulin A nephropathy and in hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA). Also, two Phase 2 trials are ongoing.

One is continuing to enroll IgA nephropathy patients and has already generated positive data in patients with IgA nephropathy and with lupus nephritis; the other is enrolling and has reported positive data in patients with HSCT-TMA and in patients with aHUS. OMS721 can be administered both intravenously and subcutaneously, and Omeros expects to commercialize each formulation of OMS721 for different therapeutic indications. In parallel, Omeros is 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 US and Europe. The FDA has granted OMS721 breakthrough therapy designation for IgA nephropathy and for high-risk HSCT-TMA, orphan drug status for the prevention (inhibition) of complement-mediated thrombotic microangiopathies and for the treatment of IgA nephropathy, and fast track designation for the treatment of patients with aHUS.

Omeros also has identified MASP-3 as responsible for the conversion of pro-factor D to factor D and as a critical activator of the human complement system's alternative pathway. The alternative pathway is linked to a wide range of immune-related disorders.

In addition to its lectin pathway inhibitors, the company is advancing its development of antibodies and small-molecule inhibitors against MASP-3 to block activation of the alternative pathway. Omeros has initiated the manufacturing scale-up process of its MASP-3 antibodies in preparation for clinical trials.