Shares of Omeros Corp. (NASDAQ:OMER) jumped 50.9% to $21.32 on Aug. 10 after it reported that six critically ill COVID-19 patients treated with its investigational lectin-pathway inhibitor, narsoplimab, recovered from the disease. The company said it will now seek government support to accelerate the drug’s large-scale manufacture. "We look forward to being able to make narsoplimab broadly available to hospitalized COVID-19 patients," said Omeros CEO Greg Demopulos.
The compassionate-use study, led by Alessandro Rambaldi in Bergamo, Italy, was the first time a lectin-pathway inhibitor was used to treat COVID-19, Omeros said. The study found that "narsoplimab down-modulates SARS-CoV-2-induced activation of the lectin pathway and endothelial cell damage, reducing thrombotic risk," according to a pre-proof article slated for publication in Immunobiology.
Omeros is already in the midst of wrapping up a rolling BLA for narsoplimab as a treatment for thrombotic microangiopathy (TMA) associated with hematopoietic stem cell transplant, where it appears to benefit patients by heading off endothelial cell injury. But as mounting research appears to suggest endothelial injury is also a key driver of COVID-19, then it seems that narsoplimab could be "a good a rational answer," Demopulos said, during a company call.
A complicated problem
When first dealing with COVID-19 in February, "we were completely unprepared," said Rambaldi, head of the department of hematology and oncology at the Papa Giovanni XXIII Hospital in Bergamo and a professor at the University of Milan. At first, "we were expecting to be dealing with a flu-like syndrome, but during the early days of the crisis, we realized that the problem was much more complicated and very different."
It soon became evident that the endothelial problem presented by the infection was the most relevant one, he said. Many patients died quite rapidly due to thromboembolism, a complication of the heart, the lungs and the CNS. And a simple assay revealed a clear clue as to why: The endothelial vasculature of COVID-19 patients was dramatically challenged during the early phase of the COVID-19 infections, as indicated by an increased number of circulating endothelial cells, he said. "That was the spark that caused me to call Dr. Demopulos," with whom he had already worked on transplant-associated TMA.
Endothelial injury, which plays a central role in transplant TMA and other problems arising from stem cell transplant, activates the lectin pathway of complement. Narsoplimab, by inhibiting that pathway through blocking its effector enzyme, MASP-2, has demonstrated "striking results" in the treatment of transplant TMA patients, Demopulos said.
Endothelial damage can also play an early and central pathogenic role in acute respiratory distress syndrome (ARDS), a severe and life-threatening symptom of COVID-19, the company said. In doing so, it activates the lectin pathway of complement. MASP-2, the lectin pathway’s effector enzyme and the target for narsoplimab, then binds the nucleocapsid protein of SARS-CoV-2, resulting in complement activation and lung injury.
All recovered, all survived
In Rambaldi's experiment, six COVID-19 patients with ARDS requiring continuous positive airway pressure or intubation received narsoplimab. The median age of the patients was 57. At baseline, circulating endothelial cell counts and serum levels of interleukin-6, interleukin-8, C-reactive protein, lactate dehydrogenase, D-dimer and aspartate aminotransferase – all markers of endothelial/cellular damage and/or inflammation – were significantly elevated. Narsoplimab treatment was begun within 48 hours of initiation of mechanical ventilation and was dosed twice weekly for two to four weeks.
All six narsoplimab-treated patients recovered, survived and were discharged from the hospital, Omeros said. In each, narsoplimab treatment was associated with rapid and sustained reduction across all assessed markers of endothelial/cellular damage and/or inflammation. In a retrospective comparison of two control groups with similar entry criteria and baseline characteristics, mortality rates were 32% and 53%, respectively, the company said.
Though not a formal clinical trial, the results have already led the company to engage in talks between Omeros and offices in the U.S. Department of Health and Human Services. The company said Monday that it’s engaged in discussions with both the Biomedical Advanced Research and Development Authority and the NIH's Accelerating COVID-19 Therapeutic Interventions and Vaccines program regarding potential funding to accelerate large-scale manufacturing to enable broader availability of narsoplimab for COVID-19 patients.
Seattle-based Omeros is also moving to raise as much as $325 million, through a sale of $125 million worth of its common stock in a public offering and $200 million in convertible senior notes, it said Monday. BofA Securities and JP Morgan are acting as the book-running managers for each of the offerings.