Omeros Announces Positive OMS721 Data in Model of Thrombotic Microangiopathy
-- Support Advancing Initial Clinical Indication of Atypical Hemolytic Uremic Syndrome --
SEATTLE, April 2, 2013 -- Omeros Corporation (OMER) today announced positive data using OMS721, the lead human monoclonal antibody in Omeros' mannan-binding lectin-associated serine protease-2 (MASP-2) program, in a well-established animal model of thrombotic microangiopathy (TMA), a disorder that occurs in the microcirculation (e.g., venules and capillaries) of the body's organs, most commonly the kidney and brain. Omeros expects to submit a European Clinical Trial Application (CTA) this quarter to initiate clinical trials evaluating OMS721. The lead indication planned for OMS721 clinical trials is atypical hemolytic uremic syndrome (aHUS), a rare but life-threatening form of TMA.
Omeros controls the worldwide rights to MASP-2 and all therapeutics targeting MASP-2, a novel pro-inflammatory protein involved in activation of the complement system – an important component of the immune system. The complement system plays a role in the inflammatory response to tissue damage or microbial infection. OMS721 selectively inhibits MASP-2, blocking the lectin pathway of the complement system while leaving intact the classical pathway, or the acquired immune response to infection. The Company has conducted a series of preclinical studies that suggest that MASP-2 inhibition may have a preventive or therapeutic effect in the treatment of aHUS, HUS, wet age-related macular degeneration (AMD), paroxysmal nocturnal hemoglobinuria (PNH), transplant-related complications, ischemia-reperfusion injury, and other immune-related disorders.
The studies reported today were conducted to support the planned initial indication for OMS721 – aHUS. In this well-established model, thrombus (blood clot) formation is induced in microvessels following phototoxic injury of the vessel wall. Using intravital microscopy, a high-resolution imaging technique that allows direct visualization of dynamic biological processes in the microcirculation in live animals, the effects of OMS721 on thrombus formation were assessed. Specifically, the study evaluated OMS721's ability to delay the time to onset of thrombus formation and to complete occlusion of the blood vessel. 100 percent of isotype-antibody control animals versus 71 percent of OMS721-treated animals showed thrombus formation, with the initiation of thrombus formation delayed approximately three-fold in the OMS721-treated group relative to control (a median of 19.0 vs. 6.8 minutes; p=0.0097). Eighty percent of control-treated animals showed complete occlusion within the observation period while only 43 percent of those treated with OMS721 occluded completely. Median time to complete occlusion was 18.0 minutes for control and 38.0 minutes for the OMS721-treated animals (p=0.0036).
"These data are impressive," stated Markus Sperandio, M.D., professor of cardiovascular physiology and microvascular disorders at the Walter-Brendel-Center of Experimental Medicine, Munich, Germany, where he conducted the TMA studies evaluating OMS721. "OMS721 looks like a promising agent to prevent thrombus formation in the microcirculation. We are planning additional studies to refine the dosing and timing of administration of OMS721 in models across a wide range of thrombotic disorders."
"We are pleased with these results and are excited to initiate the clinical program for OMS721," stated Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. "The current treatment options for aHUS are limited and, when compared to those options, we believe that OMS721 carries marked advantages that will translate to significant patient benefits. We are eager to evaluate the drug product in aHUS patients, and we remain on track to begin Phase 1 clinical trials mid-year."
About Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical Hemolytic Uremic Syndrome (aHUS) is a chronic, very rare, life-threatening disease. The condition has the hallmarks of a thrombotic microangiopathy and manifests as hemolytic anemia, thrombocytopenia and renal impairment. aHUS differs from HUS in that an infectious etiology, i.e., E. coli or streptococcal infection, is absent. Dysregulation of the complement system lies at the heart of aHUS pathogenesis, and genetic abnormalities in complement genes have been identified in greater than 60 percent of all aHUS patients. It is thought that certain precipitating factors are needed to trigger aHUS in a genetically predisposed individual. Many of the potential precipitating factors are linked to endothelial cell activation, stress or injury; all of these processes activate the lectin pathway. If untreated, most aHUS patients die or develop end-stage renal disease within one year of diagnosis. Current treatment options include plasma therapy and eculizumab, which have limitations in terms of feasibility, safety and patient convenience.
About Omeros' MASP-2 Program
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 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.
Omeros also believes that it has identified the proteins that activate the complement system's alternative pathway, 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.
About Omeros Corporation
Omeros is a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing products targeting inflammation, coagulopathies and disorders of the central nervous system. The Company's most clinically advanced product candidates, OMS302 for lens replacement surgery and OMS103HP for arthroscopy, are derived from its proprietary PharmacoSurgery™ platform designed to improve clinical outcomes of patients undergoing a wide range of surgical and medical procedures. Omeros has five clinical development programs. Omeros may also have the near-term capability, through its GPCR program, to add a large number of new drug targets and their corresponding compounds to the market. Behind its clinical candidates and GPCR platform, Omeros is building a diverse pipeline of protein and small-molecule preclinical programs targeting inflammation, coagulopathies and central nervous system disorders.
This press release contains forward-looking statements as defined within the Private Securities Litigation Reform Act of 1995, which are subject to the "safe harbor" created by those sections. These statements include, but are not limited to, Omeros' expectations regarding when it will submit a CTA for OMS721 and begin clinical trials; the diseases that may be treated by OMS721; the potential competitive advantages of OMS721; and that Omeros may have capability, through its GPCR program, to add a large number of new drug targets and their corresponding compounds to the market. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. Omeros' actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the risks, uncertainties and other factors described under the heading "Risk Factors" in the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 18, 2013. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and the Company assumes no obligation to update these forward-looking statements publicly, even if new information becomes available in the future.