18 November 2020 - - US-based Omeros Corp. (NASDAQ: OMER) has completed the rolling submission of its Biologics License Application to the US Food and Drug Administration for narsoplimab for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), the company said.

Narsoplimab targets mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of complement, and has received breakthrough therapy designation and orphan drug designation from FDA for HSCT-TMA.

This final portion of the rolling BLA submission, comprised of the BLA's clinical sections, follows the previously submitted chemistry, manufacturing and controls and nonclinical sections, which are under review by FDA.

The clinical sections are based on previously reported results of the pivotal trial of narsoplimab in HSCT-TMA in which the drug met its primary endpoint and demonstrated similarly strong response across its secondary endpoints.

Omeros has requested priority review for the BLA, and applicable regulations provide FDA up to 60 days to determine the filing and review designation for the application.

Omeros is a commercial-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market and orphan indications targeting inflammation, complement-mediated diseases, disorders of the central nervous system and immune-related diseases, including cancers.

Its commercial product OMIDRIA (phenylephrine and ketorolac intraocular solution) 1%/0.3% continues to gain market share in cataract surgery.

Omeros' lead MASP-2 inhibitor narsoplimab targets the lectin pathway of complement and is the subject of a rolling biologics license application under review by FDA for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy.

Narsoplimab is also in multiple late-stage clinical development programs focused on other complement-mediated disorders, including IgA nephropathy, atypical hemolytic uremic syndrome and COVID-19.

Omeros' MASP-3 inhibitor OMS906, which targets the complement system's alternative pathway, recently entered the clinic, and the company's PDE7 inhibitor OMS527 has successfully completed its Phase 1 trial.

Omeros' pipeline holds a group of preclinical programs including a novel antibody-generating technology and a proprietary GPCR platform through which it controls 54 new GPCR drug targets and their corresponding compounds. One of these novel targets, GPR174, modulates a new cancer immunity axis recently discovered by Omeros, and the company is advancing small-molecule GPR174 inhibitors.

Hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) is a significant and often lethal complication of stem cell transplantation.

This condition is a systemic, multifactorial disorder caused by endothelial cell damage induced by conditioning regimens, immunosuppressant therapies, infection, graft-versus-host disease, and other factors associated with stem cell transplantation.

Endothelial damage, which activates the lectin pathway of complement, plays a central role in the development of HSCT-TMA. The condition occurs in both autologous and allogeneic transplants but is more common in the allogeneic population.

In the United States and Europe, approximately 25,000 to 30,000 allogeneic transplants are performed annually.

Recent reports in both adult and pediatric allogeneic stem cell transplant populations have found an approximately 40-% incidence of HSCT-TMA, and high-risk features may be present in up to 80 % of these patients. In severe cases of HSCT-TMA, mortality can exceed 90% and, even in those who survive, long-term renal sequalae (e.g., dialysis) are common.

There is no approved therapy or standard of care for HSCT-TMA.

Narsoplimab, also known as "OMS721," is an investigational human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a novel pro-inflammatory protein target and the effector enzyme of the lectin pathway of complement.

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.

Omeros controls the worldwide rights to MASP-2 and all therapeutics targeting MASP-2.

A biologics license application has been submitted to the US FDA for use of narsoplimab in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), and the drug is in Phase 3 clinical programs for immunoglobulin A nephropathy and atypical hemolytic uremic syndrome.

The FDA has granted narsoplimab breakthrough therapy designations for HSCT-TMA and for IgA nephropathy; orphan drug status for the prevention (inhibition) of complement-mediated thrombotic microangiopathies, for the treatment of HSCT-TMA and for the treatment of IgA nephropathy; and fast track designation for the treatment of patients with aHUS.

The European Medicines Agency has granted orphan drug designation to narsoplimab for treatment in HSCT and for treatment of primary IgA nephropathy.