Omeros Reports OMS721 Inhibits Thrombus Formation in Sera from aHUS Patients

 Omeros Corporation

today announced positive data using OMS721, the lead human monoclonal antibody for its mannan-binding lectin-associated serine protease-2 (MASP-2) program, to inhibit thrombus formation in an ex vivo pathophysiologic system of human atypical hemolytic uremic syndrome (aHUS), a form of thrombotic microangiopathy (TMA). TMAs are a family of rare, debilitating and life-threatening disorders characterized by excessive thrombi (clots) in the microcirculation of the body's organs, most commonly the kidney and brain. OMS721 is currently in a Phase 2 clinical program evaluating the drug's efficacy in treating TMAs, including aHUS. The data announced today resulted from studies in a well-established experimental model of TMA aimed at assessing the potential therapeutic benefits of OMS721 in TMA using serum samples from aHUS patients with different etiologies obtained during the acute phase of disease as well as during remission. The studies were conducted by Prof. Giuseppe Remuzzi and colleagues Marina Noris and Miriam Galbusera at the Mario Negri Institute for Pharmacological Research in Bergamo, Italy, and the Clinical Research Center for Rare Diseases "Aldo e Cele Dacco" of the same institute, a European center for the study of TMA. The experimental model is based on the finding that sera from aHUS patients promote the formation of thrombi on human microvascular endothelial cells, the defining pathological feature of TMA. The studies reported today showed that OMS721 significantly inhibited thrombus formation when added to serum samples from aHUS patients obtained during the acute phase of disease (p<0.01) as well as during remission (p<0.0001). OMS721 was as effective at inhibiting thrombus formation as the positive control in the studies – soluble complement receptor 1, an agent that completely blocks the complement system. Earlier this year, Omeros reported that OMS721 also significantly inhibited complement deposition compared to control treatment in an experimental ex vivo pathophysiologic system of complement activation in TMA, again using serum samples from aHUS patients obtained during the acute phase of disease (p<0.01) and during remission (p<0.001). Prof. Remuzzi's laboratories have previously shown in the same complement-activation model that eculizumab (Soliris^®), a monoclonal antibody blocking the complement factor C5 that is approved by the FDA and the European Medicines Agency to treat patients with aHUS, also inhibited complement deposition. Data recently published indicate that the ex vivo pathophysiologic system established by Prof. Remuzzi and his colleagues may be useful in assessing the clinical effectiveness of anti-complement therapy in aHUS (Noris et al., Blood (2014) 124:1715). "We believe that the notable anti-complement and anti-thrombotic activities of OMS721 in serum samples from aHUS patients bode well for the therapeutic potential of OMS721 in thrombotic microangiopathies," stated Prof. Remuzzi, MD, FRCP, Research Coordinator at the Mario Negri Institute and international expert in the study of kidney disease who has contributed major advances to the understanding of the pathophysiology of hemolytic uremic syndrome. Having demonstrated that the lectin pathway, and MASP-2 specifically, are involved in the pathophysiology of aHUS, Prof. Remuzzi and his team are currently conducting additional experiments to understand the mechanism by which OMS721 blocks ex vivo thrombus formation in aHUS and its effect on endothelial cells, platelets and the alternative pathway of complement. "Thrombus formation is the central pathological feature of aHUS and other TMAs, so we are particularly pleased with the robust anti-thrombotic activity in serum samples from aHUS patients," stated Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. "We believe that these most recent data from Prof. Remuzzi's laboratories meaningfully de-risk our '721 Phase 2 program in TMAs, including aHUS, and we look forward to reporting preliminary efficacy and safety data from the ongoing clinical trial."