Omeros Corporation, a clinical-stage biopharmaceutical company, has announced that its Investigational New Drug (IND) application to evaluate OMS721 for the inhibition of complement-mediated thrombotic microangiopathies (TMAs) has been cleared by the US Food and Drug Administration (FDA).

OMS721 is the company's lead human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the key regulator of the lectin pathway of the immune system. Omeros announced last year that the FDA granted OMS721 Orphan Drug designation for the inhibition of complement-mediated TMAs, a family of rare, debilitating and life-threatening disorders characterized by multiple thrombi (clots) in the microcirculation of the body's organs, most commonly the kidney and brain.

FDA's clearance of the IND allows the initiation of the phase 2 programme for OMS721, which will assess the efficacy and safety of OMS721 in patients with disorders associated with lectin pathway activation. The first OMS721 phase 2 clinical trial, planned to begin later this quarter, will evaluate the effects of the drug on patients with TMAs, including atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP), and stem cell transplant-related TMA. The lectin pathway, one of the principal complement activation pathways in the immune system, is thought to play a central role in the development of TMAs, and OMS721, by targeting and inhibiting MASP-2, blocks the lectin pathway.

Last month, the company reported positive data in serum samples from aHUS patients indicating that the lectin pathway, and MASP-2 specifically, are involved in the pathophysiology of aHUS. In those studies, OMS721 significantly inhibited complement deposition both in the acute phase of the disease and during remission, and its inhibitory effect was similar to that of agents that block complement factor C5. Eculizumab (Soliris), a C5 monoclonal antibody for the treatment aHUS, is the only commercially available complement inhibitor. Omeros controls the worldwide rights to MASP-2 inhibition and to all therapeutics targeting MASP-2.

"FDA's decision clears the way for us to begin the phase 2 programme for OMS721," stated Gregory A Demopulos,  chairman and chief executive officer of Omeros. "We are excited by the data in serum samples from aHUS patients, and we look forward to reporting results from our phase 2 clinical trial in patients with aHUS and other TMAs later this year."

Omeros controls the worldwide rights to MASP-2 inhibition and to 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 appears to be unique to, and required for the function of, one of the principal complement activation pathways, known as the lectin pathway. 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 wide range of autoimmune disorders. MASP-2 is generated by the liver and is then released into the circulation. Adult humans who are genetically deficient in one of the proteins that activate MASP-2 do not appear to be detrimentally affected by the deficiency. Therefore, Omeros believes that it may be possible to deliver MASP-2 antibodies systemically and OMS721, its lead MASP-2 antibody, is designed to be self-administered by subcutaneous injection.

Omeros also believes that it has identified the proteins that activate the complement system's alternative pathway in humans, which is linked to a wide range of immune-related disorders. In addition to its lectin pathway inhibitors, the Company is advancing the development of antibodies that would block activation of the alternative pathway alone or in combination with the lectin pathway.

Omeros is a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics targeting inflammation, coagulopathies and disorders of the central nervous system.