COR-101

The fully human antibody COR-101 is the lead product of our current therapeutic antibody product pipeline.

COR-101 decreased SARS-CoV-2 virus load in the lung by more than 99 % in the Hamster COVID-10 model, and induced recovery after 2 days, compared to 7 days untreated (more information).

COR-101 was generated by antibody phage display, and it’s virus binding regions are encoded by unchanged natural human gene sequences.

To select COR-101, 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.

COR-101 development

How CORAT antibodies protect against severe COVID19

Recombinant human virus-neutralizing antibodies are the active component of the immunotherapy (also named passive vaccine). Antibodies (immunogobulins, IgG) are molecules made by our own body to protect us against infections.

The CORAT antibody neutralizes SARS-CoV2 after injection and immediately provides the protection in exactly the same way like antibodies made by our own body would do 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 sequences were taken out of a healthy donor.

Due to the long serum half time, the CORAT antibody is planned to 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 or genes encoding virus materials 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.

Why Passive Vaccination?

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 symthoms) 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 directly 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 scientific and technology partner 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 partner YUMAB already has developed numerous fully human antibodies for leading pharmaceutical companies.

CORAT antibody prevents infection with SARSCoV2 isolated from COVID19 patient

Data

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 a CORAT antibody 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)

(Data: HZI, Prof. Čičin-Šaindownload more information here)

How human antibody COR-101 neutralizes the coronavirus SARS-CoV-2

structure of COR-101
The crystal structure of COR-101 (yellow) Fab in complex with SARS-CoV-2-RBD (green). From the publication “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” doi: https://doi.org/10.1101/2020.12.03.409318

The fully human antibody COR-101 blocks SARS-CoV-2 by inhibition of ACE2 binding and prevents infection with the coronavirus. 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 (see also here). COR-101 covers an extraordinarily large area and with very high binding strength. As a result, the virus can no longer attack and penetrate the cells and multiply.

Further, 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.

Publication: Bertoglio et al. (2020) ASARS-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. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3754550

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