Second-generation mRNA-based COVID-19 vaccine candidate, CV2CoV, shows improved immune response and protective effect in preclinical study

• Preclinical study shows significantly improved immune responses of CureVacs jointly developed second generation mRNA backbone with GSK compared to CureVac's first generation mRNA backbone
• Data show high protective effect of second generation vaccine candidate, CV2CoV, during SARS-CoV-2 challenge study in animal model
• The ability of the induced antibodies to neutralize different variants, such as the beta, delta and lambda variants, was investigated

CureVac NV (Nasdaq: CVAC), a global biopharmaceutical company developing a new class of messenger ribonucleic acid (mRNA) -based transformative drugs in clinical trials, and GSK today released preclinical data investigating the immune responses and protective effects of CureVacs First generation vaccine candidate, CVnCoV, and second generation vaccine candidate, CV2CoV, during a SARS-CoV-2 challenge study in non-human primates. The study was carried out in cooperation with Dan Barouch, MD, PhD, of the Beth Israel Deaconess Medical Center and examined cynomolgus monkeys after being vaccinated with 12µg of the first or second generation vaccine candidate. It was found that compared to the first generation vaccine candidate, CV2CoV CVnCoV, innate and adaptive immune responses are better activated and thus a faster onset of the immune response, higher antibody titers and a stronger activation of B and T memory cells. CV2CoV was also able to achieve a stronger antibody neutralization of all selected variants, including the beta, delta and lambda variants. The challenge study with the original SARS-CoV-2 virus showed that the animals vaccinated with CV2CoV were better protected, as measured by the effective elimination of the viral load in the lungs and nose. The complete manuscript of the preclinical data is on the preprint server higher antibody titers and a stronger activation of B and T memory cells achieved. CV2CoV was also able to achieve a stronger antibody neutralization of all selected variants, including the beta, delta and lambda variants. The challenge study with the original SARS-CoV-2 virus showed that the animals vaccinated with CV2CoV were better protected, as measured by the effective elimination of the viral load in the lungs and nose. The complete manuscript of the preclinical data is on the preprint server higher antibody titers and a stronger activation of B and T memory cells achieved. CV2CoV was also able to achieve a stronger antibody neutralization of all selected variants, including the beta, delta and lambda variants. The challenge study with the original SARS-CoV-2 virus showed that the animals vaccinated with CV2CoV were better protected, as measured by the effective elimination of the viral load in the lungs and nose. The complete manuscript of the preclinical data is on the preprint server measured by the effective elimination of the viral load in the lungs and nose. The complete manuscript of the preclinical data is on the preprint server measured by the effective elimination of the viral load in the lungs and nose. The complete manuscript of the preclinical data is on the preprint serverbioRxiv available.

"In this animal model it has been shown that CV2CoV triggers extensive antibody and cellular immune responses that are very similar in breadth to the immune activation of an infection with SARS-CoV-2," said Dr. Igor Splawski, Chief Scientific Officer at CureVac. “The current study shows that the immune responses and the resulting protective effect of our second-generation vaccine candidate, which is based on our mRNA technology after implementation of targeted optimizations, have been significantly improved in non-human primates. This is evident both in relation to the original SARS-CoV-2 virus strain and in relation to the worrying beta and delta variants ("Variants of Concern") and the lambda variant of interest ("Variant of Interest"). "

Dr. Rino Rappuoli, Chief Scientific Officer and Head of Research and Development at GSK Vaccines said, “mRNA technology is a high strategic priority for us and we are investing significantly in a number of mRNA programs with an emphasis on working with CureVac. The strong immune response and the protective effect in the preclinical testing of the second generation mRNA backbone are very encouraging and represent an important milestone for their further development. "

Within the study, cynomolgus monkeys were immunized with 12 µg each of the respective vaccine candidate on day 0 and day 28. The induction of innate immunity was investigated on the basis of specific cytokine markers. Adaptive immune responses were assessed based on specific antibodies for the receptor binding domain, neutralizing antibodies, and B and T memory cells. The influence of "Variants of Concern" and "Variants of Interest" on neutralizing antibody titers was tested against the alpha, beta, delta, kappa and lambda variants. After challenge infection with the original virus, the elimination of the viral load in the lungs and nose of the animals was also examined.

The COVID-19 collaboration between CureVac and GSK, announced in February 2021, expands the existing strategic mRNA technology partnership that the companies entered into in July 2020. This relates to the development of new products based on CureVac's second generation mRNA technology for various infectious diseases. The optimized mRNA backbone on which this collaboration is based also has the potential for multivalent or combined vaccine formats to combat multiple virus variants in one vaccine. Following the current preclinical development of CV2CoV, a phase 1 clinical trial is expected to begin in the fourth quarter of 2021.