CureVac N.V. announced results from the final analysis of its 40,000 subject international pivotal Phase 2b/3 study (the HERALD study) of the first-generation COVID-19 vaccine candidate, CVnCoV. In the unprecedented context of 15 strains circulating within the study population at the time of final analysis, CVnCoV demonstrated an overall vaccine efficacy of 48% (vaccine 83 vs. 145 placebo) against COVID-19 disease of any severity, including single non-respiratory mild symptoms. Significant protection was demonstrated among participants in the age group of 18 to 60, with an efficacy of 53% (vaccine 71 vs. 136 placebo) against disease of any severity and across all 15 identified strains; protection against moderate to severe disease was calculated to be 77% (9 vaccine vs. 36 placebo). In the same age group, CVnCoV provided 100% protection (vaccine 0 vs. 6 placebo) against hospitalization or death. In participants above 60 years, who represented 9% of the analysed cases, the available data did not enable a statistically significant determination of efficacy. The data confirm the favorable safety profile of CVnCoV in all age groups. The study will continue to complete follow-up analyses for trial participants. Available data have been communicated to the European Medicines Agency (EMA). In total, 228 adjudicated COVID-19 cases (83 vaccine vs. 145 placebo) were assessed in the final analysis. In the age group of 18 to 60, across strains of higher prevalence, strain-dependent vaccine efficacy ranged from approximately 42% to up to 67%. Out of the 228 cases, 204 were sequenced to identify the variant causing the infection. Approximately 86% of these cases were caused by Variants of Concern (~51%) and Variants of Interest (~35%), the latter including the Lambda strain, first identified in Peru (~21%) and B.1.621, first identified in Colombia (~14%). Approximately 3% of cases were attributable to the original SARS-CoV-2 virus. The remaining 11% were caused by less-explored strains. The HERALD study, enrolled approximately 40,000 participants in ten countries in Latin America and Europe. Statistical success criteria for the final analysis were met on the basis of 228 cases, occurring at least two weeks after administration of the second dose, including 68 additional adjudicated cases compared to the pre-defined 160 cases as per trial protocol. To identify COVID-19 strains within the trial, sequencing of virus variants has been performed on 588 COVID-19 cases, of which 204 fulfilled adjudication criteria and were included in the efficacy analysis. Beyond CVnCoV, the company is developing second-generation COVID-19 vaccine candidates in partnership with GSK. These candidates are based on new mRNA backbones and include potential variants in multivalent vaccine formats as well as combination vaccines for potential protection against multiple infectious diseases in single injection. Preclinical data from the first vaccine candidate, CV2CoV, has recently been published in Nature Communications. CureVac and GSK expect to progress the second-generation vaccine candidate into clinical testing in the third quarter of 2021, with the goal of introducing the vaccine in 2022, subject to regulatory approval.