Promising Treatment for Covid-19 Enters Clinical Trials in Israeli Medical Centers

Trial at Columbia University Irving Medical Center Recruits First Patient

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Feb 24, 2021, 08:30 ET

BOSTON, Feb. 24, 2021 /PRNewswire/ -- Researchers at two major medical centers in Israel, Rambam Medical Health Care Campus and Ziv Medical Center, have initiated a Phase 2 clinical trial of a promising new treatment for COVID-19.

These trials are testing TXA27, a compound with an established safety profile. TXA127 has been developed by Boston-based Constant Therapeutics "We are examining the use of a drug based on a naturally occurring peptide called Angiotensin (1-7), that prevents cell proliferation and inflammation in the lungs," said Professor Karl Skorecki, Dean of the Azrieli Faculty of Medicine of Bar-Ilan University in the Galilee.

Coronavirus enters the human body by binding to Angiotensin Converting Enzyme 2 (ACE2) receptors, which are also responsible for producing Angiotensin (1-7). This interaction leads to a reduction in Angiotensin-(1-7) and the loss of its intrinsic protective effects.

"When the enzyme is busy acting as a receptor for the virus, it can no longer do what it is supposed to do, which is make Angiotensin (1-7)," Professor Skorecki said. "We hope that by replenishing this peptide, the lungs of patients will get back what the virus nefariously took away from them." Research has shown that respiratory failure is the leading cause of death in COVID-19, and inflammation in the lungs may lead to secondary damage of other tissues through the release of cytokines. SARS-CoV-2 directly affects the endothelial lining of blood vessels leading to hypercoagulation and stroke. In multiple animal models of acute lung injury, Angiotensin-(1-7) reduces these effects and may improve many of the symptoms associated with COVID-19, both in the acute form and in "long-COVID".

Consistently 3% of patients who contract SARS-CoV-2 in both the US and Israel are hospitalized, and many do not respond to what have become standard therapies, including steroids, antivirals and monoclonal antibodies. During this first year of the pandemic approximately 840,000 patients required hospitalization in the US.

As of this date 21 patients have been enrolled in a double-blind placebo-controlled 120-patient Phase 2 trial of TXA127 in hospitalized patients whose condition is defined as moderate and who do not need invasive ventilation. Sixty patients will receive the treatment and 60 a placebo. The FDA has allowed an IND for a second Phase 2 trial being conducted at Columbia University Irving Medical Center and New York-Presbyterian Allen Hospital. This double-blind placebo-controlled trial will enroll 100 patients.

Professor Zaid Abassi Staff Scientist at Rambam Health Care Campus and researcher at Technion Institute of Science said, "I thought if there was a decrease in Angiotensin (1-7) in the body, maybe external administration of the protein would prevent the complications caused by coronavirus, with an emphasis on improving lung damage,"

Dr. Richard Franklin, CEO of Constant Therapeutics said, "In addition to researchers in Israel and at Columbia, we have been contacted by medical centers and scientists in the US, UK, Belgium, Italy, Spain and Australia suggesting the use of TXA127 for the treatment of COVID-19 and requesting drug for trials."

Professor Skorecki estimates that the Israeli trial will be completed within four months. Coronavirus mutations would not affect the effectiveness of treatment, according to Dr. Etty Kruzel-Davila, a senior nephrologist at Rambam Health Care Campus, who is leading the trial.

Two other coronaviruses, SARS and NL63 use the same mechanism of entry as SARS-CoV-2 with the same impact on Angiotensin-(1-7) levels. Important influenza viruses, including H1N1, H5N1, and H7N9 also downregulate the activity of ACE2. "Given the previous occurrence of epidemics of such viruses, it is likely that there will be new viruses emerging that will have this same mechanism of infection." said Dr Franklin. "All of the current variants, including those appearing in the UK, South Africa, and Brazil, although behaving differently in terms of transmissibility and susceptibility to vaccines, still attach to ACE2 and should be treatable by TXA127."

Constant is currently investigating the potential to use TXA127 for the treatment of more severely ill patients in the ICU and for outpatient treatment of newly infected patients to be treated with an oral formulation of TXA127.

About TXA127
TXA127 is a pharmaceutical formulation of the naturally occurring human peptide angiotensin-(1–7). In addition to its specific effects in lung injury, TXA127 has shown therapeutic activity in animal models of chronic stroke, Duchenne Muscular Dystrophy (DMD), Limb–Girdle Muscular Dystrophy (LGMD), Congenital Muscular Dystrophy (MDC1A), Marfan Syndrome and Epidermolysis Bullosa.

About Constant Therapeutics LLC
Constant Therapeutics LLC is a private biopharmaceutical company developing drugs that target the alternative renin angiotensin system, the protective arm of the renin angiotensin system (RAS). This protective pathway involves the enzyme ACE2, its principal product, the peptide angiotensin-(1-7), and the peptide's target, the Mas receptor. Constant's lead drug candidate is TXA127. For more information on Constant Therapeutics, please visit our website at www.constanttherapeutics.com.

CONTACT (US): Rick Franklin
+1-617-245-0289
[email protected]

CONTACT (Israel): Osnat Attali-Briand (for Rambam)
+972-54-9713868
[email protected]

SOURCE Constant Therapeutics