Formycon is developing FYB207, an innovative antiviral drug for the treatment 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)
Formycon is initially developing FYB207 for hospitalized COVID-19 patients for which no sufficiently effective drugs currently exist. Other possible indications include newly infected COVID-19 patients without symptoms and preventive use, e.g., in caring facilities.
FYB207 can potentially be used to target all coronaviruses that use ACE2 as a port of entry and thus also serves as a precaution for future corona pandemics.
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. The development strategy for an accelerated approval process has already been coordinated with the Paul Ehrlich Institute (“PEI”) and the FDA through Scientific Advices in 2021.
In a follow-on Scientific Advice in May 2022, the PEI confirmed full support for the improved drug molecule for the accelerated development program. On this basis, preclinical studies are expected to be completed, the manufacturing process will be adapted to the optimized molecule, and the production of test material for stability studies and clinical trials will be carried out in 2022. Entry into clinical trials is planned for 2023.
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.