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

We are developing a potential drug candidate APN01* (alunacedase alfa), based on our proprietary ACE2 platform to address the growing global health threat of COVID-19. 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.

ACE2, and its role in respiratory diseases, was first discovered by Prof. Joseph Penninger, who founded APEIRON Biologics in 2003. Research driven by the first SARS outbreak identified and confirmed ACE2 as the cellular entry receptor for SARS-CoV-1 and in response, APN01 was developed to specifically target this receptor to prevent the binding of the spike protein. It has now been confirmed that ACE2 is also the primary cell entry receptor for SARS-CoV-2.

Directly targeting the SARS-CoV-2 virus

APN01 is a soluble recombinant form of the human angiotensin-converting enzyme 2 (rhACE2) – effectively mimicking ACE2 within the body.

ACE2 is an enzyme that regulates the Renin-Angiotensin-System (RAS), a hormone system involved in COVID-19 (SARS-CoV-2) as well as lung disorders and cardiovascular diseases more broadly.

APN01 is designed to block the SARS-CoV-2 virus from binding to the ACE2 receptor and infecting cells, while at the same time downregulating the RAS system to help prevent inflammation and organ injury – critical components involved in the cytokine storm response.

The specific targeting of SARS-CoV-2 by APN01 was recently confirmed by preclinical results published in the peer-reviewed publication CELL 2.

APN01’s proposed mechanism of action

APN01 Mode of Action

Designed to mimic ACE2, APN01 in effect has two distinct modes of action, with three potential benefits for COVID-19 patients.

APN01 has the potential to prevent cells from infection with the SARS-CoV-2 virus, reduce injury to multiple organs and additionally to treat the inflammatory reactions in the lungs caused by COVID-19.

1. Preventing infection & neutralizing the virus:
Binding of APN01 to viral spike protein prevents binding of the virus to cell surface receptors and thereby prevents infection of cells.

2. Preventing organ injury & reducing disease mediated organ pathology:
APN01 shifts the Renin-Angiotensin-System (RAS) towards repair and reduction of injuries to blood vessels and organs including the lungs, kidneys or the heart.

3. Controlling inflammation: APN01 reduces the release of pro-inflammatory cytokines and chemokines which play an important role in lung injury and cytokine storm, thereby reducing the uncontrolled inflammation triggered by SARS-CoV-2.

Based on upon this understanding, APN01 may be a viable treatment option – particularly among severe patients as it could potentially help prevent disease progression and thereby potentially help preserve critical ICU capacity by reducing the need for patient intubation.

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

A named patient use case report published in the peer-reviewed journal The Lancet Respiratory Medicine (September 25th , 2020) describes the first treatment with APN01 of a patient suffering from severe COVID-19. The 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.

Current development status of APN01

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.

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

In addition to its investigation as a potential therapeutic to combat COVID-19, APN01 has successfully completed several clinical trials in severe respiratory diseases like acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and pulmonary arterial hypertension (PAH).

*APN01 is an investigational agent and has not been approved by the U.S. Food and Drug Administration, the European Medicines Agency, or any other regulatory agencies.

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We are committed to act and imagine a world where we can prevent people dying from COVID-19.