APN01, based on the work of Dr. Josef Penninger, already shown to block viral spread in SARS
The University of British Columbia’s Life Sciences Institute, in close cooperation with APEIRON Biologics AG, a Vienna-based biotechnology company, today announced the launch of a pilot clinical trial of APN01, a potential and novel treatment for patients with severe Coronavirus infections in China.
The randomized, dual-arm trial will treat 24 patients for seven days to determine whether APN01 treatment improves outcomes in patients with severe SARS-CoV-2 infection – the virus that causes COVID-19 disease.
APN01, a drug candidate being developed by APEIRON, is based on previous work in the early 2000s, when Dr. Penninger, director of UBC’s Life Sciences Institute and Canada 150 Chair in Functional Genetics, together with Drs. Arthur Slutsky (University of Toronto) and Chengyu Jiang (Peking Medical Union College) discovered that a protein called ACE2 was the critical receptor for the SARS virus, and also protected the lung.
“As a result of SARS revealing its secrets of how it damages the lungs,” says Penninger, “it has also shown us how to develop new medicines to treat other diseases.
“Now, it turns out that the SARS-CoV-2 virus also uses ACE2 to infect cells,” adds Penninger. “So ACE2 is the rational and targeted therapy for the new epidemic. First, APN01 keeps the virus from infecting cells, and second, it should prevent lung failure and multiple organ complications, the source of most of the mortality we are seeing with COVID-19.
During the trial, which will begin February 26, participants will be treated for seven days to assess is APN01 reduces the viral load of SARS-CoV-2 virus, as well as the number of days patients endure fever. Data from the trial will be evaluated to determine if there is a need for an additional clinical trial in a larger number of patients.
An international team of Canadian, Chinese, and European experts is supporting the trial, including Penninger, cofounder of APEIRON, and the APEIRON team. The trial is being led by Dr. Yimin Li, the ICU director who fought the 2003 SARS outbreak Guangdong Province, and Dr. Nanshan Zhong, the Chair of the National COVID-19 Commission in China, while Dr. Haibo Zhang, a professor of anesthesiology and Dr. Arthur Slutsky an intensive care specialist, both based at St. Michael’s Hospital in Toronto, will analyze the trial data.
Dr. Liqun Zhang, and the team at Angalpharma Co. Ltd. in Suzhou, China have been coordinating the Chinese clinical trial with the support of dMed Pharmaceutical Co, a CRO team based in China.
APEIRON Biologics, a biotech company headquartered in Vienna, Austria, developed APN01, a soluble recombinant human ACE2 protein, that has already been tested in phase I trials in healthy volunteers and in phase II clinical trials in lung failure patients, evaluating safety and activity of the drug.
“Our team has been able to bring together this worldwide group of experts and scientists together to address this unfortunate crisis and dreadful disease,” says Dr. Peter Llwellyn-Davies, CEO of APEIRON Biologics. Our drug product, APN01 has been tested in previous clinical trials, and we are delighted and proud we can start treating infected patients in China.”
“It is great to see that the basic principles previously discovered on ACE2 and SARS infections, now turn out to be also critical for the new pandemic outbreak of the new Coronavirus,” says
Slutsky. “This is also a testament to international networks of committed experts and a testament to Canadian science and what Canada can contribute to hopefully stemming this
APN01 is a recombinant human Angiotensin Converting Enzyme 2 (rhACE2) and was developed by APEIRON for the treatment of acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and pulmonary arterial hypertension (PAH). After licensing from APEIRON in February 2010, GlaxoSmithKline plc conducted ALI, PAH and ARDS trials from 2014 to 2017, the latter being the major source of COVID-19 mortalities, the disease caused by the new corona virus 2019-nCoV. In 2019, APEIRON obtained the APN01 licenses from GlaxoSmithKline (GSK) again for further clinical development, after a strategic refocusing of GSK to oncology. The ACE2 receptor is expressed in human airway epithelia as well as lung parenchyma and was previously identified as the gateway which the SARS virus uses to infect the cells. ACE2 is also the critical receptor for the new virus 2019-nCoV to enter human cells. Thus, treatment with recombinant human ACE2 could be used to not only block viraemia but also protect lungs from injury. APEIRON currently has the full licenses, clinical data and protocol from GSK, GMP production technology and stored GMP grade rhACE2 available for immediate use in trials in China. The drug candidate is administered intravenously as an infusion and has shown safety and tolerability in over 100 patients and volunteers.
About APEIRON BIOLOGICS AG
APEIRON is a privately-held European biotech company based in Vienna, Austria, focused on the discovery and development of novel cancer immunotherapies. APEIRON received EU marketing approval for APN311 (Dinutuximab beta, Qarziba®) in May 2017 for the treatment of pediatric neuroblastoma patients and out-licensed global, exclusive rights for this product to EUSA Pharma Ltd. APEIRON now leverages its proprietary master checkpoint blockade mechanism to enable the human body’s natural defense mechanisms to fight the tumor. APEIRON’s clinical lead program APN401 is a first-in-class autologous cellular therapy to strengthen immune reactivity via an intracellular master checkpoint, Cbl-b. APEIRON’s projects and technologies are bolstered by a strong patent portfolio. APEIRON’s development expertise is validated through partnerships with leading pharmaceutical companies and academic institutions.
Photo Credit: Tybor Kulcar, IMBA