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June 29, 2020 – SALT LAKE CITY, UTAH – A new study published today in Blood, the official journal of the American Society of Hematology, sheds light on the mysterious blood clots and inflammation in patients with Novel Coronavirus (COVID-19). The peer-reviewed paper describes a new medicine that may block COVID-19 inflammation being developed by PEEL Therapeutics, a biotech company based in Utah.
The clinical study on COVID-19 was done in collaboration between scientists at PEEL Therapeutics, University of Utah Health, Cold Spring Harbor Laboratory and Weill Cornell Medical. The investigators discovered large amounts of free-floating DNA in blood collected from hospitalized patients with COVID-19. This DNA is a biomarker for Neutrophil Extracellular Traps, or NETs, that are normally released from immune cells to catch invading pathogens. The scientists found that higher levels of NETs correlated with the risk of needing a ventilator and dying from COVID-19. The study also showed that platelets formed clots mixed with NETs in the lungs of patients who died. Using a natural blocker of NETs, the scientists prevented NETs in healthy immune cells exposed to plasma from the blood of COVID-19 patients. This natural NET inhibitor was first discovered in newborn babies and is being developed by PEEL Therapeutics as a possible treatment for inflammation in COVID-19.
SARS-CoV-2, the virus that causes COVID-19, has infected over eight and a half million people worldwide and caused over 450,000 deaths. Up to fifteen percent of patients with COVID-19 will become critically ill and 1 in 20 patients will die with limited treatment options. Scientists are working to understand the excessive immune response in COVID-19 that leads to uncontrolled inflammation called cytokine storm. Equally puzzling has been the frequent description of COVID-19 patients with clotting problems that do not respond well to blood-thinners. This combination of cytokine storm and clots in COVID-19 leads to stroke, heart attack, pulmonary embolism, and acute respiratory distress syndrome (ARDS).
PEEL Therapeutics, a spinoff from the University of Utah and the Technion-Israel Institute of Technology, develops medicines inspired by natural evolution. “PEEL” is the Hebrew word for elephant, and the company began with a cancer drug based on the elephant’s ability to resist cancer. Another drug under development comes from the small protein, or peptide, that occurs in newborn infants to block inflammation from NETs and may help in the fight against COVID-19. PEEL Therapeutics works closely with scientists at University of Utah Health who discovered these natural NET inhibitors in the umbilical cord blood from newborn babies and is preparing a new class of anti-inflammatory drugs called Neutrophil Targeting Peptides (NTPs) to block NETs.
PEEL Therapeutics CEO and Co-Founder, Dr. Joshua Schiffman, is a pediatric hematologist-oncologist, and was excited for PEEL to be involved in the current COVID-19 study. “We had been working for several years on developing NTPs,” says Schiffman, “and together, with our University of Utah colleagues, we have seen a tremendous response in early testing in mice with sepsis.” Schiffman explains that Dr. Con Yost, a neonatologist at University of Utah Health and the physician-scientist to first describe neonatal NET-inhibitory factors (nNIFs), was already leading a team to explore NETs in adults with ARDS when the pandemic began. “It just made sense to look for NETs in COVID-19 patients because they have such severe cytokine storm and so many clots, and we know that NETs can cause these same types of problems in other patients with inflammation.”
For their study, 33 patients with COVID-19 admitted to University of Utah Hospital were enrolled and blood markers looking for NETs were compared to 17 healthy age- and sex-matched controls who were blood donors. Fourteen of the COVID-19 patients were admitted to the Intensive Care Unit (ICU), and half of these required mechanical ventilation. The NET biomarkers in the COVID-19 patients correlated with disease severity and progression, and some of the highest levels of NETs in the study were found in patients who eventually died. The COVID-19 patients with the highest NET markers were the same patients with the lowest blood oxygen levels, indicating poor lung function and the need for ventilators. Study members at Cold Spring Harbor Laboratory and Weill Cornell Medical discovered unusual mini-clots containing platelets and NETs scattered in the lungs from patients that had succumbed to COVID-19. Immune cells taken from COVID-19 patients in the hospital were extremely activated and released 50-fold more NETs compared to healthy controls. The plasma from COVID-19 patients also triggered a very robust NET response in healthy neutrophil cells in laboratory tests. These NETs were almost completely blocked by nNIF, the anti-inflammatory NTP found in newborn babies.
PEEL Therapeutics continues to work with collaborators in Utah and Israel to move NTPs as a first-in-class drug to human patients with COVID-19, with early and promising preclinical studies. They also are working with ARUP, a commercial clinical laboratory, to introduce blood NET levels as a test for COVID-19 patients. Along with the academic scientists who participated in this study, PEEL believes that blocking NETs may represent a new and extremely effective approach to reduce the immune system’s dangerous response to COVID-19. Targeting NETs may be the most effective way to block the widespread clotting and cytokine storm. Says Schiffman, “Although PEEL Therapeutics is a young biotech company, our new drug comes from hundreds of thousands of years of evolution in newborns and may represents nature’s best solution to COVID-19 inflammation.”
PEEL Therapeutics, Inc.
PEEL Therapeutics, Inc. is an emerging biotech that delivers evolution-inspired medicines to improve patient lives. The PEEL pipeline originates from assets inspired by the evolution of elephants, plants and humans for the treatment of cancer and inflammatory diseases, including COVID-19. PEEL is supported by private investors and philanthropic charities including Closer To Cure Foundation, Animal Cancer Foundation, and Soccer for Hope Foundation. The company is located in Salt Lake City, Utah and Haifa, Israel.
University of Utah Health
University of Utah Health provides leading-edge and compassionate medicine for a referral area that encompasses 10% of the U.S., including Idaho, Wyoming, Montana and much of Nevada. A hub for health sciences research and education in the region, U of U Health has a $373 million research enterprise and trains the majority of Utah’s physicians, including more than 1,250 health care providers each year at its Schools of Medicine and Dentistry and Colleges of Nursing, Pharmacy and Health.
Cold Spring Harbor Laboratory
Founded in 1890, Cold Spring Harbor Laboratory has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,100 people including 600 scientists, students and technicians.