APN01 – Our work on a potential drug candidate for COVID-19 treatment

We are developing a potential drug candidate APN01, based on our proprietary ACE2 platform to address the growing global health threat. APN01 is ideally suited to prevent the infection with SARS-CoV-2, reduce injury to multiple organs and mitigate the deleterious consequences of established viral infection.

APN01 (rhsACE2) is a soluble recombinant version of ACE2. It was developed in response to the first SARS outbreak in the early 2000s by Prof. Josef Penninger, who founded APEIRON Biologics in 2003. Like SARS-CoV-1, that caused this outbreak, SARS-CoV-2 also uses ACE2 as the primary cell entry receptor. APN01 binds viral particles and thereby block them from binding to the ACE2 receptor on the cell surface, hence preventing cell entry and infection with the virus.

Virus neutralization as one mode of action of APN01. APN01 is the soluble form of the viral cell entry receptor ACE2. Binding of APN01 to viral spike protein prevents binding of the virus to the cell surface receptor and thereby prevents infection of the cell.

In addition, ACE2 is an enzyme regulator of the Renin-Angiotensin-System (RAS), a disease relevant system involved in COVID-19 and more generally a wide group of acute lung disorders and cardiovascular diseases. Based on its function to negatively regulate RAS, APN01 can reduce injury to multiple organs including the lung, kidneys and the heart, and reduces disease mediated organ pathology.

Furthermore, in a unique triple approach, APN01 triggers reduction of inflammatory cytokines and chemokines, both of which play an important role in lung injury and cytokine storm.

Taken together, APN01´s triple mode of action has a unique advantage compared to virtually all other treatments by providing the best scientific rational among specific therapeutics for COVID-19, surpassing other treatment options by acting at all relevant disease stages from the first viral infection to the development of severe lung injury and the consequences of the infection.

The safety and tolerability of APN01 has been shown in several Phase 1 and Phase 2 trials.

A double-blind, randomized, placebo-controlled Phase 2 clinical trial for APN01 was initiated in April 2020 in several European countries (UK, Germany, Austria, and Denmark) and later also in Russia. In total 24 clinical centres were included. Patient recruitment will be completed in 2020. Efficacy data are expected by early 2021.

A named patient use case report published in the peer-reviewed journal The Lancet Respiratory Medicine (September 25^th , 2020) describes the first treatment with APN01 of a patient suffering from severe COVID-19. The encouraging data published show the expected observations of an adaptive immune response, a rapid loss of virus load and reduction in inflammatory mediators, and the development of high titers of neutralizing antibodies against SARS-CoV-2 leading to a significant clinical improvement of the patient treated.

Once clinical efficacy is proven we are aiming for an accelerated approval in close cooperation with the European Medical Association (EMA).

THE LANCET publishes promising data of APEIRON’s APN01 (rhsACE2) to treat COVID-19 in named patient use.

Our work on a potential drug candidate for COVID-19.

Human soluble ACE2 improves the effect of remdesivir in SARS‐CoV‐2 infection.  EMBO Molecular Medicine, Published November 12^th, 2020.

Case report “Human recombinant soluble ACE2 in severe COVID-19. The Lancet Respiratory Medicine, Published September 25^th, 2020.

Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell; Published April 24^th, 2020.