Omeros Announces Completion Of IgA Nephropathy Cohort In OMS721 Phase II Clinical Trial

SEATTLE--(BUSINESS WIRE)--Omeros Corporation (NASDAQ: OMER) today announced completion of the IgA nephropathy cohort and reported additional positive results from the first stage of the company’s Phase 2 clinical trial of OMS721 for the treatment of serious kidney disorders. All patients in the cohort have now completed the OMS721 treatment and follow-up periods. The additional Phase 2 results in IgA nephropathy patients expand on the data reported earlier this year and further demonstrate marked and statistically significant improvement in urine protein levels (proteinuria). Proteinuria reduction is associated with slowing progression of kidney functional loss, and greater proteinuria reductions are associated with progressively better prognoses. OMS721 is Omeros’ lead human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the complement system’s lectin pathway.

“I have never seen the clinical responses that I’ve observed in IgA nephropathy patients treated with OMS721,” stated Geoffrey Block, M.D., Director of Clinical Research at Denver Nephrology and Principal Investigator of the trial. “All of these patients had significant renal impairment when they entered the trial and each patient dramatically improved. The improvements in these patients continued to increase after the end of treatment and persisted following completion of the trial. As an active clinical investigator, given the strength of these data, I am working hard to move this promising drug through the clinical trial process.”

The first stage in this Phase 2 trial includes four different types of complement-associated kidney diseases: IgA nephropathy, membranous nephropathy, lupus nephritis, and complement component 3 (C3) glomerulopathy. All patients had pre-existing renal impairment. To meet enrollment criteria, patients must have high levels of proteinuria despite well-controlled blood pressure with stable dosing of renin-angiotensin system inhibitors and ongoing (at least three months) corticosteroid treatment prior to receiving OMS721. Patients in this cohort are treated open-label with OMS721 for a total of 12 weeks and then followed post-treatment for six weeks. The trial endpoints are measured throughout the treatment and follow-up periods and assess the effect of OMS721 on urine protein measures that are predictive of kidney failure, namely urine albumin-to-creatinine ratio (uACR) and total 24-hour urine protein excretion.

All IgA nephropathy patients had Stage 3B chronic kidney disease and three of the four patients had nephrotic range proteinuria. All patients demonstrated marked improvement in uACRs and in 24-hour urine protein excretion while concurrently tapering corticosteroid treatment. The mean baseline uACR in these patients was 1,457 mg/g and reached 332 mg/g at the end of the follow-up period (77 percent decrease; p = 0.026). One patient’s uACR normalized by the National Kidney Foundation criterion. Results of 24-hour urine protein excretion were highly consistent with the uACR results, with a reduction from a mean of 3,935 mg/day at baseline to a mean of 1,067 mg/day at the end of the follow-up period (73 percent decrease; p = 0.013). All patients achieved partial remission based on proteinuria and one patient with nephrotic range proteinuria achieved a 95 percent reduction, reaching reference laboratory-established normal urine protein levels. All patients also were able to eliminate or greatly reduce their corticosteroid dosing.

“The OMS721 results in patients with IgA nephropathy continue to be striking,” said Jonathan Barratt, Ph.D., F.R.C.P., Professor of Renal Medicine in the Department of Infection, Immunity & Inflammation at University of Leicester and Honorary Consultant Nephrologist at Leicester General Hospital. “The degree of improvement observed with OMS721 is the largest I have seen and I expect will result in significant improvement in renal outcomes.”

Consistent with all other OMS721 clinical trials, no significant safety concerns have been observed. The most commonly reported adverse events in this trial are fatigue and anemia.

“We are pleased with the continued consistency of the results seen in these patients treated with OMS721,” stated Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. “Despite being an orphan disease, IgA nephropathy is the most common primary glomerular disease worldwide, and we are keenly focused on this indication for OMS721. We are aggressively advancing to our Phase 3 clinical trial and look forward to beginning patient enrollment as soon as possible.”

No treatments are approved for IgA nephropathy. With an annual incidence of approximately 1 per 100,000, it is estimated that 1 in 1,400 persons in the U.S. will develop IgA nephropathy in his or her lifetime. As many as 40 percent of them will develop end-stage renal disease.

While preparing for its Phase 3 clinical trial in IgA nephropathy, Omeros is continuing to conduct the second stage of its ongoing Phase 2 clinical trial in which OMS721 is evaluated in non-steroid-treated patients with IgA nephropathy. As previously reported, 4 of 5 lupus nephritis patients in the Phase 2 trial also demonstrated marked reduction in 24-hour urine protein levels (mean reduction of 69 percent) with OMS721 treatment. Further analyses are in progress.

About Omeros’ MASP Programs

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 is the effector enzyme of the lectin pathway, one of the principal complement activation pathways. 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 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. OMS721 is Omeros’ lead human MASP-2 antibody. Following discussions with both the FDA and the European Medicines Agency, a Phase 3 program for OMS721 in atypical hemolytic uremic syndrome (aHUS) is in progress. Also, two Phase 2 trials are ongoing. One is evaluating OMS721 in glomerulonephropathies, which has generated positive data in patients with immunoglobulin A (IgA) nephropathy and with lupus nephritis; the other has reported positive data both in patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy (TMA) and in those with aHUS. In addition to potential intravenous administration, Omeros plans to commercialize OMS721 for one or more therapeutic indications as a subcutaneous injection and is also developing small-molecule inhibitors of MASP-2. Based on requests from treating physicians, Omeros has established a compassionate-use program for OMS721, which is active in both the U.S. and Europe. The FDA has granted OMS721 both orphan drug status for the prevention (inhibition) of complement-mediated TMAs and fast track designation for the treatment of patients with aHUS.

Omeros also has identified MASP-3 as the critical activator of the human 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 its development of antibodies and small-molecule inhibitors against MASP-3 to block activation of the alternative pathway.

About Omeros Corporation

Omeros is a biopharmaceutical company committed to discovering, developing and commercializing both small-molecule and protein therapeutics for large-market as well as orphan indications targeting inflammation, coagulopathies and disorders of the central nervous system. Part of its proprietary PharmacoSurgery^® platform, the company’s first drug product, OMIDRIA^® (phenylephrine and ketorolac injection) 1% / 0.3%, was broadly launched in the U.S. in April 2015. OMIDRIA is the first and only FDA-approved drug (1) for use during cataract surgery or intraocular lens (IOL) replacement to maintain pupil size by preventing intraoperative miosis (pupil constriction) and to reduce postoperative ocular pain and (2) that contains an NSAID for intraocular use. In the European Union, the European Commission has approved OMIDRIA for use in cataract surgery and lens replacement procedures to maintain mydriasis (pupil dilation), prevent miosis (pupil constriction), and to reduce postoperative eye pain. Omeros has clinical-stage development programs focused on: complement-associated thrombotic microangiopathies; complement-mediated glomerulonephropathies; Huntington’s disease and cognitive impairment; and addictive and compulsive disorders. In addition, Omeros has a proprietary G protein-coupled receptor (GPCR) platform, which is making available an unprecedented number of new GPCR drug targets and corresponding compounds to the pharmaceutical industry for drug development, and a platform used to generate antibodies.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, which are subject to the “safe harbor” created by those sections for such statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions and variations thereof. 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, risks associated with product commercialization and commercial operations, unproven preclinical and clinical development activities, regulatory oversight, intellectual property claims, competitive developments, litigation, and 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 May 10, 2017. 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, even if new information becomes available in the future.