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Development of SARS-CoV-2 neutralising antibodies against COVID19
18.11.2020 - CORAT lead product COR-101 ready for clinical trials
CORAT Therapeutics CEO Dr. Andreas Herrmann today reports the conclusion of the production campaign providing the first larger batch of COR-101 ready for the patients: „We are extremely happy and would like to thank everybody who helped to make this happen so quickly. With acute case numbers rising fast, CORAT hopes to make a difference by providing an option soon to directly treat the Coronavirus-Infected. We hope that the clinical studies now can commence very soon.“
Fighting COVID19 with recombinant fully human Antibodies neutralizing SARS-CoV2
CORAT is a consortium of academic and industrial partners with the mutual goal to develop a passive vaccination immunotherapy against COVID-19 employing novel fully human monoclonal antibodies neutralizing SARS-CoV2.
A large set of more than 750 human monoclonal antibodies recognizing SARS-CoV2 Spike (S) protein isolated by antibody phage display from human antibody libraries from healthy donors and convalescent COVID-19 patients underwent a fast track development process to identify lead molecule with optimal drug features for a passive vaccine. The best antibody currently is in production to be clinically tested soon as immunotherapy to treat acute COVID-19. Moreover, this drug candidate may also be applied in a prophylactic scheme to protect medical care personnel or impaired patients. Innovative and state of the art methods are used to manufacture the drug candidate in much shorter time than ever done so far while keeping all necessary safety and quality requirements for medical use substances.
How CORAT antibodies protect against severe COVID19
Recombinant human virus-neutralizing antibodies are the active component of the immunotherapy (also passive vaccine). Antibodies (immunogobulins, IgG) are molecules made by our own body to protect us against infections.
The CORAT antibody neutralize SARS-CoV2 after injection and immediately provides the protection in exactly the same way like antibodies would do from our own body once they are generated by the infection or by vaccination. The CORAT antibody stops the virus and protects the patients until their immunity generates their own antibodies. This drug should be very well tolerated, because it is identical to human antibodies (“fully human”) - actually, its exact sequences were taken out of a healthy donor.
Due to the long serum half time, the CORAT antibody could be given in an early and acute stage of SARS-CoV2 infection with immediate antiviral effect and long protection until the body has the time to produce enough of its own IgG.
How are CORAT antibodies different from a typical vaccine?
A typical vaccine ("active vaccine”) consisting of dead or partial virus material cannot heal COVID19 patients. The reason is that active vaccines induce an immune response - typically the generation of antibodies (IgG) - like the infection does itself. However, the development of protecting antibodies takes up to 2-3 weeks, too long for patients with a severe infection to survive. Therefore, patients that are already infected do not benefit from such an active vaccine. The same is true for medical care personnel in emergency situations, because immunological protection starts only several weeks after the vaccination.
In contrast, CORAT antibody immunotherapy (also named "passive vaccine") supplements the not yet existing antibodies in the patient's body from the very time of injection, thus helping to lower the virus burden immediately. An active vaccine can protect healthy persons after some weeks, but it does not help patients already infected. Further, it cannot provide immediate protection to risk groups and exposed medical care personnel. CORAT antibodies can fill this treatment gap and thus perfectly complement virus-based vaccines.
As it will take many years to completely vaccinate the world's entire population, acute severe cases will be seen in our clinics for a long time to come, and a medication to help these patients is urgently needed.
Serum therapy is established since 120 years and well tolerated
Serum therapy uses (un-defined) mixtures of antibodies from immunized animals or convalescent patients to neutralize pathogens
Introduced by Emil v. Behring in the late 19th century (First Nobel prize for medicine 1901), countless children cured (diphtheria)
although effective, side effects of animal serum therapy were seen (which are completely avoided by fully human CORAT design)
IVIG (pooled human IgG from plasma donors) is still broadly used
Recent results demonstrate the efficacy of neutralising antibodies against SARS-CoV-2, with a 72% reduction in hospitalisation (development of more severe symthomas) in the BLAZE-1 study by Lilly (NCT04427501).
Recombinant neutralising antibodies are a proven class of drugs
There is already an approved antibody neutralizing drug against lung viruses, which eliminates the disadvantages of serum therapy, and shows how well antibodies can be tolerated.
Synagis® (palivizumab): Prevention of respiratory syncytial virus (RSV) infection, approved to be used as a precautionary measure in premature babies, infants and toddlers with previous illnesses (prophylactic administration).
Technology behind CORAT
CORAT antibodies are made by Nobel-prize awarded molecular biology technique "antibody phage display" to isolate human monoclonal antibodies from blood that are indistinguishable from our own bodies antibodies - with one difference: they prevent SARS-CoV-2 infection
To minimize potential side effects, every biomolecule in a CORAT medication is made from a gene directy obtained from human donors, i.e. it has already been produced before in a healthy person - there are no synthetic parts, no chemical modifications etc. involved.
CORAT member TU Braunschweig has already successfully generated neutralising antibodies to other deadly viruses, for example our antibody X10H2 against SudanEbola Virus (protective in in vivo tests , PNAS. 2020 117:3768-3778 ), VEEV, WEEV, Marburg Virus, and many pathogenic Toxins.
Some of these antibodies, e.g. our antibodies against diphtheria toxins, performed better in inhibition than the currently used serum-derived clinical standard treatment, as confirmed by the NIBSC, see (Sci Rep. 2020, 10:571)
CORAT antibody prevents infection with SARSCoV2 isolated from COVID19 patient
Infection of cells (in cell culture) with SARS-CoV2 isolates from a COVID19 patient lead to their lysis, indicated by rounding and loss of confluence (upper left panel). Uninfected cells (upper right) grow normally (no dead round dots). Lower right: Adding the CORAT antibody from Yumab to infected cells completely protected the cells from infection for 5 days, while a negative control antibody (lower left panel) did not protect the cells (Fotos: light microscopy)
Originally initiated by Prof. Stefan Dübel, YUMAB founder and head of the Biotechnology Department of the University of Braunschweig and his colleague Prof. Michael Hust, together with Prof. Gundram Jung of University of Tübingen, CORAT expanded to a consortium of more than 30 scientists and clinicians from academic institutions and industry. CORAT members represent competence from infection research, antibody development and manufacturing to bedside and have joined forces to supply acute COVID19 patients with a well-tolerated treatment to eliminate SARS-CoV2.
Since 16.6.2020, the preclinical and clinical development is coordinated by CORAT Therapeutics GmbH, a company founded for that purpose with support by the State of Lower Saxony.
Antibodies for COVID-19 research und diagnostics
...finally, please feel free to visit Abcalis, another award winning spin off of TU Braunschweig, providing animal free antibodies against the SARS-CoV2 spike and N proteins (already 100% compliant to the new recommendations of EU (EURL ECVAM JRC120199) / EU Directive 2010/63/EU).
Abcalis' anti-SARS-CoV-2 antibodies are currently in development for rapid antigen detection tests with partner companies.
Prof. Dr. Stefan Dübel / Prof. Dr. Michael Hust Technische Universität Braunschweig, Institute of Biochemistry, Biotechnology and Bioinformatics Spielmannstr. 7, 38106 Braunschweig, Germany Phone: +49-531-391-5731, Fax: +49-531-391-5763 firstname.lastname@example.org / email@example.com
Fully human antibodies from healthy donors that neutralise SARS-CoV-2 (Manuscript in revision):
Bertoglio, F., Meier, D., Langreder, N., Steinke, S., Rand, U., Simonelli, L., Heine, P. A., Ballmann, R., Schneider, K.-T., Roth, K. D. R., Ruschig, M., Riese, P., Eschke, K., Kim, Y., Schaeckermann, D., Pedotti, M., Kuhn, P., Zock-Emmenthal, S., Wöhrle, J., Becker, M., Grashoff, M., Wenzel, E. V., Russo, G., Kröger, A., Brunotte, L., Ludwig, S., Fühner, V., Krämer, S. D., Dübel, S., Varani, L., Roth, G., Cicin-Sain, L., Schubert, M. & Hust, M. (2020) SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface. bioRxiv doi: 10.1101/2020.06.05.135921
Review (german language)
Dübel, S., Hust, M., Frenzel, A. & Schirrmann, T. (2020) Rekombinante, vollständig menschliche Antikörper zur Behandlung akuter COVID-19. BIOSpektrum (Springer-Verlag, Heidelberg) 4.20, 444-446. DOI: 10.1007/s12268-020-1404-4