Formycon is developing FYB207, an innovative antiviral drug for the treatment and prophylaxis of COVID-19 based on a long-acting ACE2-IgG-Fc fusion molecule.
Current development status
In vitro laboratory studies
Mode of action
SARS-CoV-2 and other coronaviruses use the protein ACE2 on the surface of human cells as a portal of entry for respiratory infections. The viral spike-1 protein binds to ACE2 on the surface of the target cells. After docking, the virus is taken up into the cell.
Laboratory studies showed that the addition of soluble ACE2 blocked the coronaviruses SARS-Cov-2 and SARS-CoV, preventing infection of cells. ACE2 also has a natural enzyme activity in the cardiovascular system that provides potential protection for the lungs, heart and kidney from threatening organ failure. Formycon has therefore fused the human ACE2 protein with the constant part of human immunoglobulin to create an innovative COVID-19 drug (FYB207) that is protected against viral mutations, completely prevents cell infection in vitro, and can potentially be used against all coronaviruses that use ACE2 as a portal of entry for cell infection.
SARS-CoV-2 infection pathway
Composition of the FYB207 fusion protein
FYB207’s mechanism of action
Possible fields of application (indications)
FYB207 can potentially be used to target all coronaviruses that use ACE2 as a port of entry. The potential indication area of the innovative drug ranges from preventive administration (e.g.: in nursing homes) to the use in newly infected COVID-19 patients without symptoms to hospitalized COVID-19 patients. For people who are immunodeficient due to pre-existing conditions, for example, and cannot be effectively vaccinated, FYB207 could be an effective treatment option.
Due to the potential organ protective function through ACE2 enzyme activity, another indication for FYB207 would be Acute Respiratory Distress Syndrome (ARDS) of various etiologies.
Our development work
Different variants of the virus blocker were investigated in laboratory scale for manufacturability, stability and virus inhibition. A recently published study on the neutralization of SARS-CoV-2 variants-of-concern Alpha (B.1.17) and Beta (B.1.351) by Formycon’s ACE2 fusion protein FYB207, performed by Formycon together with its academic partners Prof. Dr. Ulrike Protzer, Chair of Virology, and Prof. Dr. Johannes Buchner, Chair of Biotechnology, Technical University of Munich (TUM) (Research Square Preprint: https://www.researchsquare.com/article/rs-459941/v1), shows efficient in vitro neutralization of the coronavirus variants in the picomolar range. The study was conducted with two drug candidates (FYB207a, FYB207b) of the ACE2 fusion protein and builds on previously published data of four FYB207 drug candidates published by Formycon in collaboration with the TUM scientists (BioRxiv Preprint: https://doi.org/10.1101/2020.12.06.413443). Recent studies with FYB207a show that Formycon’s ACE2 fusion protein also has strong binding to the viral spike protein of the SARS-CoV-2 Delta variant (B.1.617.2). In summary, these laboratory data demonstrate that FYB207 retains its full antiviral potential even in the rapidly spreading SARS-CoV-2 variants-of-concern.
The poster presentation for the international “Keystone Symposia – Antibodies and Vaccines as Drugs for COVID-19” can be found here.
Based on preclinical studies conducted in 2021, Formycon was able to make defined proprietary modifications to the FYB207 molecular structure that resulted in significant improvements in half-life and efficacy. In addition, in toxicity studies completed in the second quarter of 2023, FYB207 showed good tolerability.
Project status and next steps
With FYB207, a promising platform has been created that neutralizes all tested COVID variants in vitro to 100%. Due to its mechanism of action, FYB207 is very likely to maintain its neutralizing effect against future COVID variants. The long half-life and good tolerability of the compound would suggest both prophylactic and therapeutic use of FYB207.
Changed overall conditions
On May 5, 2023, the World Health Organization (WHO) lifted the international health emergency caused by the SARS-CoV-2 virus, and COVID-19 currently plays very little role in daily life. This results in, among other things, a difficult recruitment environment for conducting clinical trials.
Formycon will continue to develop FYB207 in a resource-efficient manner, attend scientific advice meetings with regulatory authorities and continue international patent applications. At the same time, additional funding opportunities for the further development of the product in preparation for future pandemic events (“Pandemic Preparedness”) are being evaluated. Therefore, as of today, Formycon will not conduct any self-initiated clinical trials.
As part of the 22nd Pharma Trend Image & Innovation Awards, which were presented in September 2021
under the patronage of Bavarian Health Minister Klaus Holetschek, MdL, Formycon’s COVID-19 drug development FYB207 received the award “The Most Innovative Product®” in the category of Leap Innovations. In this category companies that will receive funding from the German Federal Ministry of Education and Research (BMBF) or the Free State of Bavaria for the development of COVID-19 therapies in 2021 were eligible to apply. In July 2021, Formycon received the commitment of the Bavarian Ministry of Economic Affairs, Regional Development and Energy (StMWi) for up to 12.7 million euros to fund the further development of the COVID-19 drug FYB207.