SEATTLE, Feb. 10, 2011 /PRNewswire/ -- Omeros Corporation (Nasdaq: OMER) today announced that research on the antifibrinolytic agents it is developing has been published in the February 11, 2011 issue of the Journal of Biological Chemistry and selected by the editors as one of the top one percent of papers reviewed by the Journal in terms of significance and overall importance. This work from the laboratory of S. Paul Bajaj, Ph.D., demonstrates that unique antifibrinolytic agents can be derived from tissue factor pathway inhibitor-2 (TFPI-2). Omeros recently announced that it holds an exclusive license to these agents.
The authors of this paper exploited structural differences between the fibrinolytic enzyme plasmin and enzymes of the coagulation cascade to design a plasmin-selective inhibitor to replace Trasylol®, which was withdrawn from the market in 2008. Because plasmin degrades fibrin clots, a drug that inhibits plasmin may have potential utility for reducing blood loss due to trauma or surgery.
Prior to withdrawal from the market for safety concerns, Trasylol® had been shown in a number of studies to be more effective at reducing blood loss than the other two most commonly used antifibrinolytic agents on the market today, tranexamic acid and epsilon aminocaproic acid. While Trasylol® is a potent inhibitor of plasmin, it is non-selective. In addition to plasmin, it significantly inhibits kallikrein and Factor XIa, two enzymes important in promoting clotting, and their inhibition can increase bleeding. Trasylol® was found to be associated with a number of safety issues, including increased mortality. Further, it is a bovine protein associated with anaphylactic reactions. While the specific cause of increased death remains unknown, an often-cited explanation is the lack of specificity of Trasylol®.
A single domain of TFPI-2, referred to as KD1, inhibits plasmin but, like Trasylol®, also inhibits kallikrein and Factor XIa. Dr. Bajaj and her colleagues demonstrate that a minimal change to the sequence of the KD1 protein increases its activity against plasmin approximately 6-fold while dramatically reducing its inhibition of kallikrein and Factor XIa by more than 100-fold. Because the variant KD1 proteins developed by the authors and exclusively licensed to Omeros are more selective than Trasylol®, they could provide more effective bleeding control with fewer side effects. Additionally, as a human protein derivative, these agents are expected to reduce the potential for immunological side effects.
The paper shows the variant KD1 reduced blood loss in a rodent model of surgical bleeding by 85 percent relative to saline treatment, demonstrating an antifibrinolytic effect at least equal to Trasylol®. Similar antifibrinolytic activity of a related variant KD1 also controlled by Omeros was confirmed by other researchers using human plasma evaluated by thromboelastography. Thromboelastograms are used clinically to assess the level of fibrinolysis in patients during surgical procedures at risk for extensive blood loss.
Importantly, the authors also found that the variant KD1 does not slow blood clotting as measured by the partial thromboplastin time (aPTT), a standard indicator of blood's ability to coagulate. Conversely, Trasylol® increased aPTT by 60 percent, which could significantly prolong bleeding in trauma and surgical patients.
Omeros believes the efficacy and improved selectivity of the variant KD1 provides a novel approach to the control of bleeding from surgery and trauma. Omeros has initiated scale-up activities of its lead antifibrinolytic compound in preparation for clinical trials.
About Omeros' Antifibrinolytic Program
Omeros is developing a series of novel antifibrinolytic agents for the control of blood loss during surgery or resulting from trauma. Omeros' agents are designed to selectively inhibit plasmin, the enzyme responsible for fibrinolysis and dissolving blood clots, while avoiding significant inhibition of kallikrein and Factor XIa, important enzymes in the coagulation cascade. These agents could provide a superior replacement for the antifibrinolytic agents Trasylol® (aprotinin), tranexamic acid and epsilon aminocaproic acid.
About Omeros Corporation
Omeros is a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing products focused on inflammation and disorders of the central nervous system. The Company's most clinically advanced product candidates 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 ongoing clinical development programs, including four from its PharmacoSurgery™ platform, the most advanced of which is in a Phase 3 clinical program, and one from its Addiction program. Omeros may also have the near-term capability, through its GPCR program, to add a large number of new drug targets 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, bleeding 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. 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 and include the ability of Omeros' antifibrinolytic agents to provide more effective bleeding control with fewer side effects than other agents. 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 Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 4, 2010. 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.
SOURCE Omeros Corporation