A University of British Columbia investigator led an international team that has discovered an experimental drug that effectively blocks the cellular door to SARS-CoV-2 used to infect its hosts (humans). The group previously offered the first genetic evidence that Angiotensin converting enzyme 2 (ACE2) is the critical receptor for SARS-CoV and that ACE2 protects the lungs from injury—hence pointing to the molecular rational for severe lung failure and associate death because of SARS-CoV infections. This important work results from a collaboration of prominent academic researchers and companies such as Vancouver’s STEMMCELL Technologies and individuals and institutions from Spain, Canada, and Sweden’s Karolinska Institutet. This multinational research effort concludes that an investigational treatment called APN01 may be capable of inhibiting COVID-19 by reducing the SARS-CoV-2 load that penetrates the lungs and other organs. A Vienna Austria-based biotech named Aperion Biologics will now take APN01 into clinical trials in Europe.
The research findings were recently published in Cell, reflecting the ongoing research of a heavy-hitting multi-national team of researchers. This group claims they provided the first genetic evidence of the importance of ACE2 in association with SARS-CoV-2, the virus behind the COVID-19 pandemic. The team points out that ACE2 is identified as a key receptor for SARS-CoV-2 infections, and hence the possibility of inhibiting this interaction could be used to treat patients with COVID-19. The team’s study reveals that clinical grade human recombinant soluble ACE2 (hrsACE2) reduces SARS-CoV-2 recovery from Vero cells by a factor of 1,000-5,000. They highlight an equivalent mouse rsACE2 had no effect. Based on this and other findings, the team declared that hrsACE2 can materially block early stages of SARS-CoV-2 infections.
What is ACE2?
A protein on the surface of the cell membrane, ACE2 is now front and center in the COVID-19 pandemic as a key receptor for the spike of glycoprotein found in SARS-CoV-2. As mentioned, members of this research team first identified ACE2 and discovered that in living organisms, ACE2 is the key receptor for SARS, the viral respiratory illness recognized as a global threat in 2003. The team linked the protein to both cardiovascular disease and lung failure.
The Drug: APN01
The researchers point that the experimental drug called APN01 (human recombinant soluble angiotensin-converting enzyme 2—hrsACE2) will soon go into clinical trials by the European biotech venture called Aperion Biologics. Dr. Art Slutksy, a scientist at the Keenan Research Centre for Biomedical Science of St. Michael’s Hospital and a University of Toronto professor and part of the international research collaboration—believes APN01 may be as useful as effective antiviral therapy.
The Study Published in Cell
The research team found that the experimental hrsACE2 inhibited the coronavirus load by a factor of 1,000-5,000. Using organoids grown from human stem cells, the team developed engineered replicas of human blood vessel and kidneys to demonstrate that the virus can directly infect and duplicate itself in these tissues. This data point, reports the University of British Columbia faculty of medicine website, evidences the development of this disease and showcases how severe cases of COVID-19 is associated with multi-organ failure as well as lead to cardiovascular damage. The team found that clinical grade hrsACE2 reduced the SARS-CoV-2 infection in these engineered human tissues (organoids).
The research was supported in part by the Canadian federal government via emergency funding focused on accelerating the development, testing, and implementation of measures to tackle the COVID-19 pandemic.
Who is Aperion Biologics?
Based in Vienna Austria, Aperion Biologics is a privately-held European venture focusing on the discovery and development of novel cancer immunotherapies. They received EU marketing approval for APN311 in May 2017 for the treatment of pediatric neuroblastoma patients and out-licensed global, exclusive rights to this product to EUSA Pharma Ltd. The Austrian firm has a number of investors. Peter Llewellyn-Davies serves as CEO.
Their key projects and technologies are strengthened by a strong patent portfolio with broad territorial coverage. Aperion’s development expertise is validated through partnerships with leading global pharma companies and academic centers.
Current COVID-19 Development efforts
The company is developing APN01, a recombinant human Angiotensin Converting Enzyme 2 (rhACE2) in development for the treatment of PAH and ALI/ARDS. They have initiated a Phase II clinical trial in Austria, Germany and Denmark for the treatment of COVID-19.
The APN01 Study
According to reports, although the research has thus far been focused on cell cultures and organoids, Aperion Biologics is planning to sponsor a clinical pilot study of severe COVID-19 patients in China. The same drug has been tested against lung diseases in a Phase II clinical trial.
TrialSite News reviewed EudraCT and found a APN01 study targeting COVID-19: categorized as number of 2020-001172-15, the study started April 3, 2020 and is sponsored by Apeiron Respiratory Therapies. It will test APN01 (recombinant human angiotensin-converting enzyme 2 or rhACE2) as a treatment for patients with COVID-19. Patients must be hospitalized with COVID-19 and be between the ages of 35 and 85. For more information about the drug, see the link.
Lead Research/Investigator for underlying Study published in Cell
· Josef Penninger, MD, professor, University of British Columbia faculty of medicine, director of the Life Sciences Institute and the Canada 150 Research Chair in Functional Genetics, UBC
· Nuria Montserrat, PhD
· Haibo Zhang, PhD, MD
· Art Slutsky, PhD, MD
· Ali Mirazimi, PhD Karolinska Institutet