4/23/2021 - First COVID-19 patients treated with COR-101 drug developed in Braunschweig, Germany.
Effective drugs against COVID-19 remain scarce in the current coronavirus pandemic. Even though the focus for months has been primarily on enabling rapid vaccination, there will be many people in the future who cannot be vaccinated, for example, due to concomitant diseases, or in whom the vaccination effect fails. Therefore, it is essential to quickly develop specific drugs for the treatment of COVID-19 disease.
The Corona Antibody Team (CORAT) of TU Braunschweig, led by Prof. Michael Hust and Prof. Stefan Dübel, and the biotechnology company YUMAB GmbH in Braunschweig have developed the virus-neutralizing antibody COR-101, which is highly effective against SARS-CoV-2 in laboratory tests. For the clinical development of COR-101, CORAT Therapeutics GmbH was founded with the support of the state of Lower Saxony, which has now started the first clinical trials in collaboration with t the University Hospital of Tübingen. Further clinical study centers are located in Braunschweig, Stuttgart (Robert Bosch Hospital), Leipzig and Dresden. The Phase Ib/II study is being conducted at these sites. In Phase-I, the tolerability of the antibody is initially being investigated in four dose cohorts. Phase II results on efficacy may form the basis for a marketing authorization application for the drug. Initial interim results are expected in the summer.
The antibody COR-101 differs in one important respect from the antibody preparations previously approved in the USA, which were procured by the German Federal Ministry of Health: COR-101 is specifically designed to treat hospitalized moderately to severely ill patients, for whom the U.S. antibodies must not be used because of their side effects. COR-101 avoids these side effects through a different, specially adapted molecular design.
Dr. Bernd Althusmann, Lower Saxony Minister of Economic Affairs, comments: "The promising antibody drug COR-101 shows that research made in Lower Saxony can provide an important building block on the way out of the pandemic. The clinical test phase that started yesterday gives hope that the Braunschweig project can soon save lives."
more about the Mechanism of action of COR-101 here (animation) and here (crystal structure)
29.04.2021 - Videoin DW television about COR-101 and CORA Therapeutics, featuring Dr. Andre Frenzel, CORAT Chief Scientific Officer
March 16, 2021 - CORAT Therapeutics GmbH obtained regulatory authorization for clinical phase I/Ib trial with the SARS-CoV-2 neutralizing human antibody COR-101.
The study (ClinicalTrials.gov ID: NCT04674566) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, first-in-human, phase I/Ib study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of COR-101 in hospitalized patients with moderate to severe COVID-19.
"We are very happy to have reached this crucial step in COR-101 development. Many thanks to the support of the State of Lower Saxony and our private investors. We feel confident that COR-101 can fill the gap in the medical need for the treatment of hospitalized COVID-19 patients that have moderate and severe symptoms, where no other specific treatment is available at this time worldwide. The development of specific therapeutics to treat COVID-19 diseases is next to vaccination and testing an important pillar to effectively fight the pandemic., comments Dr. Andreas Herrmann, CEO of CORAT.
March 11, 2021 - Neutralizing anti-SARS-CoV-2 antibodies from immune cells of healthy donors
An international research team of the Technische Universität Braunschweig and the Helmholtz Centre for Infection Research (HZI), led by the Department of Biotechnology of the TU Braunschweig, reported the development of virus-neutralizing antibodies against SARS-CoV-2 in the journal Nature Communications. These antibodies prevent the viruses from entering host cells and were isolated from an antibody gene library that had already been produced from immune cells of healthy donors before the pandemic. The study shows how, in the future, active substances to previously unknown, emerging viruses can be produced very quickly without the need for patient-derived material.
18. Februar 2021 - A team of researchers from the Technische Universität Braunschweig, together with partners from the EU consortium ATAC (Antibody Therapy Against Corona), has published the results of studies on the longevity of the immune response of COVID-19 patients in the medical journal "Med" published by Cell Press.
December 18, 2020 - Human SARS-CoV-2 neutralizing antibody COR-101 demonstrates high efficacy in a COVID-19 animal model and is ready to be used in clinical studies to treat COVID-19 patients
COR-101 decreased virus load in the lung by more than 99 %
COR-101 induced recovery after 2 days, compared to 7 days untreated
CORAT Therapeutics GmbH today reports the successful conclusion of hamster disease model tests of their lead candidate COR-101 against COVID-19. "Our antibody induced recovery of SARS-CoV-2 infected hamsters within two days. In contrast, without treatment, the hamsters only started to reach the same health status after a full week." comments Dr. Andreas Herrmann, CEO of CORAT Therapeutics. Treatment with COR-101 substantially reduced the weight loss after infection, which indicates the general health state. But since the main life-threatening effects of the virus are happening in the lung, the virus titer was measured directly in this organ which mainly contributes to lethality of SARS-CoV-2.
Dr. Herrmann says: "We are especially happy to report that COR-101 drastically reduced the amount of SARS-CoV-2 in the lung. Already after three days, an average of less than 1 % of the virus titer of the untreated control group could be detected after treatment with COR-101. This confirms the excellent neutralizing capability that we already measured in the laboratory. It demonstrates that COR-101 efficiently neutralizes the virus in a living organism and prevents disease progression".
In that respect, Dr. Herrmann also emphasized the difference in effector mechanisms compared to other antibodies: "In contrast to plasma therapy and the currently emergency approved antibodies in the US, our recombinant antibody is especially designed not to induce overshooting immune responses which contribute to the lethality in the lung. We achieved this by carefully removing the respective signals from the molecule before starting its production."
4.12.2020 - CORAT today published how COR-101 blocks SARS-CoV-2 and prevents infection with the coronavirus. The fully human antibody COR-101 showed an IC50 of 0.56 nM in a plaque-based live SARS-CoV-2 neutralization assay. The crystal structure of COR-101 in complex with SARS-CoV-2-RBD was solved at 2.0 A resolution showing that the antibody binds at the same region as the human coronavirus receptor ACE2 to SARS-CoV-2-RBD. In contrast to other published anti-SARS-CoV-2 antibodies, the binding of STE90-C11 is not blocked by known virus mutations, endowing COR-101 with higher intrinsic resistance to those possible escape mutants.
CORAT CEO Dr. Andreas Herrmann explains: "We know that a vaccine does not work in every person, and this is especially observed in older people. There are patients with other diseases that cannot be vaccinated as well. Unfortunately, these are precisely the two groups of people who usually have a higher risk of developing COVID-19. This is where COR-101 should help. Since COR-101 permanently occupies the essential contact point between the virus and our body, the virus can no longer use its "spike" proteins to infect us. We therefore expect COR-101 to be able to help all those who already have COVID-19 but whose immune system was unable to initiate its own antibody response."
Unlike the typical vaccines currently under investigation, antibody drugs do not require sophisticated freezing logistics, they are very stable and robust molecules. A century ago, doctors carried vials of antibodies in their pockets for weeks without refrigeration, so that they were always ready for use against tetanus or diphtheria, for example. COR-101 is therefore expected to have much simpler and cheaper logistics for the distribution than RNA vaccines.
1.12.2020 - In an event with Economics Minister Dr. Althusmann, Dr. Sabine Johannsen, State Secretary for Science and Culture and Stefan Muhle, State Secretary in Lower Saxony’s Ministry of Economics, Labour, Transport and Digitisation, CORAT Therapeutics won this year’s startup Award „Durchstarterpreis“ for corona solutions of the State of Lower Saxony.
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 was produced 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 member YUMAB already has developed numerous fully human antibodies for leading pharmaceutical companies.
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
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