CORAT (Corona Antibody Team)

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Worldwide study on efficacy of cross-vaccinations

In a second study, serum samples from COVID-19 convalescents and people immunized with mRNA vaccines (BioNTech, Moderna) or inactivated vaccines (Sinovac, Sinopharm) were examined. It was shown that the amount of antibodies in the blood against the envelope protein of SARS-CoV-2 started to decrease about three months after the second vaccination. However, boost immunization again increased the amount of specific antibodies, even to higher levels than immediately after the second vaccination. This could be shown for all four virus variants of concern (VOC): the original Wuhan variant, as well as Beta, Delta and Omicron. For the Wuhan variant, the number of immune cells (B and T lymphocytes) reacting against the virus was also determined. Here again, boost immunization resulted in an impressively improved immune response. The highest antibody levels were found in triple mRNA vaccinated and – most important – also in those vaccinated first with an “inactivated vaccine” and then boosted with an mRNA vaccine.

Press release (engl.) / Pressemeldung (deutsch) on virus infectivity

Press release (engl.) / Pressemeldung (deutsch) on cross vaccination efficiency

Original Study on virus infectivity

Original Study on cross vaccination efficiency

(the manuscripts are not yet peer-reviewed and  should not be relied upon without context to guide clinical praxis or health related behaviour and should not be reported in news media as established information without consulting multiple experts in the field)

ATAC consortium website

Braunschweig, February 1, 2022 - Dept. of Biotechnology joins COFONI.

The COVID-19 Research Network Lower Saxony (COFONI) is funding thirteen interdisciplinary collaborative projects in Lower Saxony with 5.97 million euros to find new medications against SARS-CoV-2 and to investigate the causes and long-term consequences of a COVID-19 disease. In this renewed project funding round, COFONI has now included the Biotechnology Department of the Technical University of Braunschweig as a new research partner. We are working on better prediction of future variants of SARS-CoV-2 and improved medications against it (project PREMUS, Prediction of Escape Mutants).

more info (TUBS magazine)

COFONI press release

Braunschweig, Sept 6, 2021 - Substantial support for CORAT Therapeutics by the German federal government

Federal Secretary of Research Anja Karliczek and Federal Secretary of Health Jens Spahn announced today the funding of CORAT through the programme "Clinical Development of Care-Related COVID-19 Drugs and Their Manufacturing Capacities" by BMG and BMBF.

Federal Research Minister Anja Karliczek explains: "For several weeks now, the delta variant of the SARS-CoV-2 virus has clearly shown us that we will unfortunately have to expect that people will continue to fall ill with COVID-19 in the future. Even with widespread availability of COVID-19 vaccines, not all people will be able to receive vaccination. Therefore, more effective drugs are needed to treat the ill."

This renewed support for the clinical development of our antibody COR101 aims to ensure that candidates for new drugs that have been successfully tested in clinical phases I and II reach patients in Germany as quickly as possible. This is intended to promptly expand the options for treating COVID-19 in the long term in line with patient needs.

Federal Secretary of Health  Jens Spahn stated:
"At the moment, only vaccination against Corona helps. But we also want to take the horror out of the pandemic in the long term. That's why we are supporting the development of new drugs so that we can continue to treat Corona patients well in the future. And we are investing in the future because in doing so we are also strengthening Germany as a biotechnology research and development location."

Press Release No. 179/2021 from BMG and BMBF (PDF)

Braunschweig, July 7, 2021 - CORAT Therapeutics GmbH announces partnership with Dermapharm Holding SE as strong strategic partner for the further development of the antibody COR-101 discovered at TU Braunschweig

For the fast and efficient delivery of its innovative drug COR 101 against COVID-19, CORAT Therapeutics GmbH announces the partnership with Dermapharm Holding SE, a manufacturer of branded pharmaceuticals. The partnership is intended to accelerate clinical development and facilitate the expansion of COR-101 production to make the drug available to patients more quickly.

"Currently, there is no approved, effective, antiviral-specific treatment for hospitalised patients with moderate to severe COVID-19 symptoms. While vaccines will remain the most important tool in fighting the pandemic, they will not be able to completely prevent the occurrence of severe cases of the disease. Therefore, this therapy is another tool that is needed. By acquiring the equity investment in CORAT we are not only providing the funds needed to accelerate the development process, but also our expertise in manufacturing antibody drugs," said Dr Hans-Georg Feldmeier, CEO of Dermapharm Holding SE.

press release

Braunschweig, Germany, June 22, 2021 - CORAT antibody COR-101 binds and inhibits all B.1.617 SARS-CoV-2 variants, including the fast proliferating “delta” variant

The newest laboratory tests indicate that COR-101 binds and inhibits the particularly aggressive new „delta” variant B.1.617.2, which is rapidly replacing the “alpha” variant B.1.1.7. On May 10th, the WHO classified the B.1.617.2 SARS-CoV-2 variant, first detected in India, as “of concern”. According to current data from the European Centre for Disease Prevention and Control (ECDC) the “delta” variant B.1.617.2 has replaced previous SARS-CoV-2 variants, including the “alpha” variant B.1.1.7, currently prevalent in Germany. According to ECDC analysis, the mutations likely increase transmissibility and decrease neutralization by convalescent plasma and currently approved therapeutic antibodies, explaining the sharp increase in the number of cases in India in recent weeks. The currently used vaccines obviously have different efficacies against the newly emerging variants. Also, while vaccines can protect healthy people, they cannot cure people already suffering from COVID-19; moreover, not everyone responds to vaccination. For these patient groups, CORAT Therapeutics GmbH is developing a drug that has an effect against SARS-CoV-2 directly.

press release

original publication

Braunschweig, June 03, 2021 - CORAT secures 12,7 Mio € from Lower Saxony State, private investors, and the German Ministry of Research and Education (BMBF)

NBank Capital and private investors from Braunschweig, each having participated in previous financing rounds, renewed their investments. The current round of financing includes additional new investors from Braunschweig. Additionally, CORAT Therapeutics GmbH is to receive up to seven million euros from the federal funding program „Research and development of urgently needed therapeutics against SARS-CoV-2“ to support clinical development of COR-101. The goal of the current financing round is to secure funding for a Phase II clinical trial with the antibody drug candidate COR-101.

Lower Saxony State Secretary of Economics, Dr. Bernd Althusmann, comments:

"CORAT has completed all the necessary development steps on schedule so far. Now, it is important to maintain the fast development and to continue with the necessary clinical trials without delay. The government of Lower Saxony is excited to continue this success story."

Download press release

CORAT Therapeutics website

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."

Further details:

press release of CORAT Therapeutics

Website of CORAT Therapeutics

more about the Mechanism of action of COR-101 here (animation) and here (crystal structure)

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.

read more...

original publication (open access)

16.7.2020 - Fraunhofer ITEM and Corat Therapeutics GmbH start accelerated production of a passive vaccine against COVID-19.

• press release

What we do.

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. Thanks to innovative approaches and the most modern methods, we were able to provide the drug candidate (COR-101) in a much shorter time than was previously possible, with all the necessary safety and quality requirements for drugs controlled by the PEI (Paul Ehrlich Institute, responsible for clinical testing). We have thus generated a drug based on an endogenous human substance that is being tested in clinical trials as an immunotherapy (passive vaccine) for the treatment of acute COVID-19. In contrast to other antibodies against SARS-CoV-2, COR-101 may be used in particular for hospitalized patients. However, if successful, this drug could also be used prophylactically to protect medical caregivers, pre-diseased patients or at-risk populations.

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's mode of action and general structure represents the human antibodies (“fully human”) we develop by ourselves after an infection - actually, its encoding sequences were taken out of a convalescent COVID-19 patient.

Due to the long serum half time, the CORAT antibody could also 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.

Other antibody drugs have already demonstrated the principle of virus neutralisation and are emergency approved in the USA. However, our COR-101 has some advantages over these antibodies due to its modified Fc region, which does not further stimulate the exaggerated immune response that is problematic in COVID-19 patients. Consequently, it is approved to be tested for the treatment of hospitalized COVID-19 patients with moderate to severe disease where the other products are not approved to be used.

How are CORAT antibodies different from a typical vaccine?

Federal Research Secretary Anja Karliczek: "In addition to the availability of vaccines, the successful development of effective therapeutics is crucial to managing the corona pandemic in the long term. Even with a high vaccination rate, we must unfortunately expect that people will continue to contract COVID-19. " (Source: PM 14.06.2021 BMBF).

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 really 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.

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.

Why CORAT?

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
• The (emergency) approvals of several antibody preparations against SARS-CoV-2 in the USA prove the general efficacy of neutralizing antibodies against SARS-CoV-2. Antibodies are thus the first specific substances that have been successfully developed worldwide against the new virus.

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.

Who we are: the team

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 rapidly expanded to a consortium of more than 30 scientists and clinicians from academic institutions and biotech and pharma industry. CORAT members represent competence from infection research, antibody development, preclinical testing and manufacturing to bedside and have joined forces to supply acute COVID19 patients with a well-tolerated treatment to eliminate SARS-CoV2.

Prof. Michael Hust (TU Braunschweig) is part of the EU Horizon2020 COVID19 consortium "ATAC". We are also grateful for rapid emergency funding from the Land Niedersachsen, and funding by the Deutsche Herzstiftung e.V., Frankfurt a.M.

Since 16.6.2020, the preclinical and clinical development is pursued by CORAT Therapeutics GmbH, a company founded for that purpose as a spin off of YUMAB with support by the State of Lower Saxony. Please refer to their website for most current informations.

References

For the most recent list of Publications, please also check here. Selected Papers:

Development of human antibody COR-101 (clinical development: CORAT Therapeutics)

• Bertoglio, F., Fühner. V., Ruschig, M., Heine, P.A., Rand, U., Klünemann, T., Meier, D., Langreder, N., Steinke, S., Ballmann, R., Schneider, K.-T., Roth, K.D.R., Kuhn, P., Riese, P., Schäckermann, D., Korn, J., Koch, A., Zock-Emmenthal, S., Becker, M., Scholz, M., Moreira, G.M.S.G., Wenzel, E.V., Russo, G., Garritsen, H.S.P., Casu, S., Gerstner, A., Roth, G., Hermann, A., Schirrmann, T., Dübel, S., Frenzel, A., Van den Heuvel, J., Čičin-Šain, L., Schubert, M. and Hust, M. (2020). A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients by phage display is binding to the ACE2-RBD interface and is tolerant to known RBD mutations. Cell Reports 36: 109433 DOI:10.1016/j.celrep.2021.109433

Fully human SARS-CoV-2 neutralising antibodies from healthy donors:

• 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.   Nature communications 12, 1577 (2021) (open access)

Immune response to SARS-CoV-2 Infections in patients

• Schubert, M., Bertoglio. F.,  Steinke, S. et al: Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant in comparison to the original Wuhan strain and the Beta and Delta variants. (Preprint) (summary/press release)
• Marcotte, H., Piralla, A., Zuo, F., Du, L., Cassaniti, I., Wan, H., Kumagai-Braesh, M., Andréll, J., Percivalle, E., Sammartino, J.C., Wang, Y., Vlachiotis, S., Attevall, J., Bergami, F., Ferrari, A., Colaneri. M., Vecchia, M., Sambo, M., Zuccaro, V., Asperges, E., Bruno, R., Oggionni, T., Meloni, F., Abolhassanni, H., Bertoglio, F., Schubert, M., Calzolai, L., Varani, L., Hust, M., Xue, Y., Hammarström, L., Baldanti. F. & Pan-Hammarström, Q. (2021). Immunity to SARS-CoV-2 up to 15 months after infection. bioRxiv https://doi.org/10.1101/2021.10.08.463699
• Sherina, N., Piralla, A., Du, L., Wan, H., Kumagai-Braesh, M., Andréll, J., Braesch-Andersen, S., Cassaniti, I., Percivalle, E., Sarasini, A., Bergami, F., Di Martino, R., Colaneri, M., Vecchia, M., Sambo, M., Zuccaro, V., Bruno, R., Oggionni, T., Meloni, F., Abolhassani, H., Bertoglio, F., Schubert, M., Byrne-Steele, M., Han, J., Hust, M., Xue, Y., Hammarström, L., Baldanti, F., Marcotte, H. and Pan-Hammarström, Q. (2021) Persistence of SARS-CoV-2 specific B-and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection. Med 2: 281-295, DOI: 10.1016/j.medj.2021.02.001
• Brondino, N., Bertoglio, F., Forneris, F., Faravelli, S., Borghesi, A., Damiani, S., Provenzani, U., Nola, M., Olivola, M., Caviglia, M., Politi, P., Fusar-Poli, L. & Fusar-Poli, P. A (2021). A pilot Study on Covid and Autism: Prevalence, Clinical Presentation and Vaccine Side Effects. Brain Sci. 11(7):860. doi: 10.3390/brainsci11070860

Rapid SARS-CoV-2 antigen production in insect cells

• J. Korn, D. Schäckermann, T. Kirmann, F. Bertoglio, S. Steinke, J. Heisig, M. Ruschig, G. Rojas, N. Langreder, E. Wenzel, K. Roth, M. Becker, D. Meier, J. van den Heuvel, M. Hust, S. Dübel & M. Schubert (2020) Baculovirus- free insect cell expression system for high yield antibody and antigen production. Scientific Reports,  7;10(1):21393. doi: 10.1038/s41598-020-78425-9