University of British Columbia & International Team Discover rsACE2 may Inhibit COVID-19 & Trial to Commence

Apr 4, 2020 | Angiotensin Converting Enzyme 2 (rhACE2), Aperion Biologics, Coronavirus, COVID-19, Investor Watch, News, Positive Results

University of British Columbia & International Team Discover rsACE2 may Inhibit COVID-19 & Trial to Commence

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).

Funding

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

Call to Action: Interested in the European clinical trial assessing APN01? See the link and contact the Vienna, Austria-based sponsor.

8 Comments

  1. John

    Blocking the ACE receptors looks to me to be the best way to stop the proliferation of the virus.

  2. Jeff K

    In the meanwhile, while we wait for the drug trials to finish, what does this mean for people who take ACE inhibitors to control their blood pressure? Should they stop taking them?

    • TrialSite

      Dear Jeff,
      We can only report on this research and cannot offer any medical advice. We do suggest that if a particular study is of relevance, such as may be the case here, that you mention to your physician. We note this is early stage research and hence we cannot make any conclusions but we should all be aware of such studies as we don’t necessarily find them reported on in as many forums.
      Regards Publisher

    • Sam Akbari

      ACE2 is identified as the key for SARS-Cov2 to infect cells. The ACE2 inhibitors are considered to be the path to treat or block the SARS-Cov2 to attach the cell. Hence being on ACE inhibitors seems to be beneficial.

      • Adam VanWert

        I think this is a great idea. Please confirm whether participants in the study will receive inhaled ACE2, or parenteral, or both? I think inhaled is the best chance for preventing infection, to coat the virus before infection. Systemic ACE2 will have many other effects on physiology, and some of those may be undesirable.

        • TrialSite

          Dear Adam,
          First thanks for visiting TrialSite News. We appreciate the comments as well.
          The study is now published in Clinicaltrials.gov and will be parenteral (only intravenous). We are not sure why but we have reached out to the sponsor (Apeiron Biologics of Austria) as we would like to invite them on to our podcast to discuss the study. If we can secure them for the show we will notify you.
          Again thanks for being part of the TrialSite Network!

          Best Regards,
          Publisher

  3. Majid Dehshiri

    I strongly believe that this method (Human recombinant soluble ACE2) is the best way to cover the COVID-19 to be detach to lung cells and prevent the cells become infected by this virus. What a noble pathway to neutralize this damn Corona virus. That is really a very smart prevention. Awesome job guys.

    • TrialSite

      Dear Majid,
      We believe this group of researchers may be on to something big–we are hoping. But there are studies to commence. Aperion Biologics out of Vienna Austria will be conducting a clinical trial listed in Europe to investigate APN01. We will watch carefully and hopefully this approach can work. The world needs it!
      Regards,
      Publisher

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