Through our innovative and cutting-edge research, our world-class team has achieved scientific advances that no other group has accomplished, delivering new classes of therapeutics to treat patients with severe and life-threatening diseases and disorders. Omeros is advancing novel research and development programs for small-molecule and protein therapeutics to address both orphan and large-market indications. Our current areas of focus include complement-mediated diseases, central nervous system disorders and immuno-oncology. Tackling challenging diseases and disorders, we are targeting and exclusively control a broad range of previously untapped receptors and enzymes. The end result is first-in-class therapeutics designed to improve and save the lives of patients.
Research Areas
Complement-Mediated Disease
The complement system is an important part of the immune system and protects against invasive pathogens as well as damaged cells inside the body. When triggered, the various components of complement cooperate to generate an immune response that fights infection and clears damaged or dead cells, maintaining healthy function of the body’s systems. There are three distinct pathways of complement, each uniquely activated:
- Classical pathway: activated by antigen-antibody complexes
- Lectin pathway: activated by lectin binding of carbohydrate patterns on the surfaces of damaged cells and microbes
- Alternative pathway: constitutively active and amplifies classical and lectin pathway activation
Over- or under-activation (i.e., dysregulation) of this important system, however, can be harmful and is associated with increased vulnerability to infections and non-infectious diseases, including autoimmune disorders, chronic inflammation, thrombotic microangiopathy, and cancer. The involvement of the complement system in these and other diseases makes it a promising therapeutic target.
Narsoplimab (also known as OMS721) is being actively studied in a number of complement-mediated diseases including stem cell transplant-associated thrombotic microangiopathy (TA-TMA), IgA nephropathy, atypical hemolytic uremic syndrome (aHUS), and others.
Endothelial Injury Syndromes
Endothelial injury syndromes encompass a range of disorders associated with hematopoietic stem cell transplantation. Stem cell transplantation is used to treat a wide range of blood-related cancers, severe types of anemia and a variety of life-threatening immune disorders. Across all of these, the pretransplant chemotherapy regimens cause significant inflammation and endothelial damage. Then, as part of the stem cell transplant procedure, patients must undergo conditioning drug regimens followed by immunosuppressive therapy, each causing even more inflammation and endothelial damage. Components of endothelial injury syndrome associated with stem cell transplantation include thrombotic microangiopathy (TMA), veno-occlusive disease (VOD) and diffuse alveolar hemorrhage (DAH). Graft-versus-host disease (GvHD), a common complication of stem cell transplant, and infection also cause significant endothelial damage.
Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (TA-TMA)
Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a significant and often lethal complication of stem cell transplants occurring in up to 39% of patients undergoing allogeneic HSCT1,2. This condition is a systemic, multifactorial disorder caused by endothelial cell damage induced by infection, GvHD, and marrow ablative agents used as part of stem cell transplantation. Activation of the complement system – primarily the lectin complement pathway – by endothelial damage plays a central role in the development of TA-TMA.
There are currently no approved products for the treatment or prevention of TA-TMA. We are developing narsoplimab, our antibody against MASP-2 (the effector enzyme of the lectin pathway), to treat TA-TMA.
1Postalcioglu M, Kim HT, Obut F, et al. Impact of thrombotic microangiopathy on renal outcomes and survival after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2018;24:2344-2353.
2Jodele S, Davies SM, Lane A, et al. Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: A study in children and young adults. Blood. 2014;124:645-653.
IgA Nephropathy
IgA nephropathy is the most common form of primary glomerulonephritis globally and is responsible for 10% of all dialysis patients worldwide. Up to 50% of IgA nephropathy patients develop end-stage renal disease and require dialysis within 20 years of diagnosis.1,2 Given the deleterious effects of steroids, there remains an unmet need for an alternative treatment option for IgA nephropathy.
Narsoplimab is our lead antibody targeting MASP-2, the effector enzyme of the lectin pathway of complement. We are developing narsoplimab for multiple indications, including IgA nephropathy.
1Hastings MC, Bursac Z, Julian BA, et al. Life Expectancy for Patients From the Southeastern United States With IgA Nephropathy. Kidney Int Rep. 2017;3(1):99-104.
2F P Schena. Am J Med. 1990;89(2):209-15.
Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical hemolytic uremic syndrome is a rare, chronic genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and progressive kidney injury. While aHUS manifests most commonly in the kidney, the central nervous and gastrointestinal systems are also affected. The prognosis is poor, with progression to end-stage renal disease in up to half of aHUS patients.
We are developing narsoplimab, our antibody against MASP-2 (the effector enzyme of the lectin pathway), to treat aHUS. Improvements in markers were observed in a Phase 2 clinical trial, and a Phase 3 clinical program is underway.
Lupus Nephritis
Lupus nephritis is an inflammatory kidney disease caused by systemic lupus erythematosus (SLE), an autoimmune disorder in which the body’s immune system attacks its own cells and organs. Kidney damage is common in SLE patients and may lead to kidney failure over time.
In a Phase 2 clinical trial, narsoplimab, our antibody against MASP-2 (the effector enzyme of the lectin pathway), reduced proteinuria by an unprecedented 70%. We plan to initiate a Phase 3 program for narsoplimab in lupus nephritis.
Leading Translational Research in Complement-Mediated Disease
In 2018, Omeros entered into a research collaboration with the University of Cambridge to establish the Omeros Center at Cambridge for Complement and Inflammation Research (OC3IR). One of the OC3IR’s priorities will be to characterize further the role of the complement system in endothelial injury, which is implicated in a wide range of diseases, including thrombotic microangiopathies and glomerulonephropathies. The Center will also facilitate collaborative links between Omeros and other leading academic research laboratories in the field of complement and inflammation research.
Central Nervous System Disorders
Addiction
Substance addiction, including nicotine, cocaine, opioid and alcohol dependence, has an estimated societal cost of nearly $1 trillion annually in the US alone. Currently marketed drugs for addiction are, at best, only partially effective.
We discovered – and exclusively control – the link between phosphodiesterase 7 (PDE7) and any form of addiction or compulsive disorder. We have shown that our PDE7 inhibitor OMS527 blocks both craving and relapse across animal models of nicotine, cocaine, opioid and alcohol addiction as well as binge eating. PDE7 inhibitors also appear to avoid a major drawback of all currently marketed anti-addiction drugs – the depression of pleasure derived from other activities (e.g., social interaction, sex, sports, etc.) – which is responsible for poor patient compliance. Also, PDE7 inhibitors have been shown to be nonaddictive in animal models.
Immuno-oncology
Omeros has created and is evaluating a number of novel immunotherapeutics that harness the body’s own immune system to fight cancer. Derived from our G Protein-coupled Receptor (GPCR) program, which currently includes 54 distinct targets, our immuno-oncology program holds the potential to modulate unique pathways to fight a broad range of solid tumors and hematologic malignancies. Learn More
While immuno-oncology to date has focused on cell surface checkpoints, we are developing combinations of inhibitors of intracellular targets, optimizing T cell conditioning to yield potent tumor killing and a more sustained antitumor response.
One application of our proprietary technology is adoptive T cell and CAR T therapies, combining inhibitors of GPR174, adenosine A2, and potentially other targets to limit the negative impact of immunosuppressive signaling on the function of T cells. This greatly enhances interleukin-2 production and skews the cells toward a central memory phenotype, preventing relapse associated with a lack of memory T cells, a significant shortcoming of many currently marketed immunotherapies.
Beyond GPR174, we also have initiated innovative programs to target more globally immunosuppressive signaling in T cells, which could provide physicians and their patients yet another wholly new class of Omeros immuno-oncology therapeutics with significant advantages over existing therapies (e.g., PD-1/PD-L1 checkpoint inhibitors).
