CanSino Biologics Inc. announced that, the Group ' s COVID-19 mRNA vaccine CS-2034 (the "CS-2034") has achieved positive interim data in a clinical trial evaluating the safety and immunogenicity of the heterologous CS-2034 booster. CS-2034 is a COVID-19 mRNA vaccine with protection against existing variants. Results of pre-clinical studies showed that, such vaccine can induce high-titer neutralizing antibodies againstmultiple SARS-CoV-2 variants of concern identified by the World Health Organization.

Compared with the original strain-based COVID-19 vaccines, CS-2034 can elicit neutralizing antibodieswith better cross-variant reactivity, and is expected to provide more effective protection against infections caused by circulating variants. To date, CS-2034 is in phase IIb clinical trial stage, and its current progress is in line with expectations. The next stage of research and development work will be planned according to future epidemic situation, national immunization strategy, review policies and the positive clinical data obtained so far.

CLINICAL STUDIES AND PRINCIPAL RESULTS The research is a randomized, blinded and parallel controlled clinical study to evaluate the safety and immunogenicity of heterologous boosting with CS-2034 in adults aged 18 years and above who have received three doses of COVID-19 inactivated vaccine. The clinical trial started in October 2022 in Jiangsu province, and is in active long-term follow-up period. A total of 433 adults who had received 3 doses of the COVID-19 inactivated vaccine at least 6 months ago were enrolled in the trial and were divided into 2 groups, namely group A and group B. The participants in group A were further divided into 2 age subgroups, one with adults aged 18-59 years and the other with adults over 60 years (160 participants each), and randomized at a 3:1 ratio to receive a dose of CS-2034 (0.3 ml volume per dose) or COVID-19 inactivated vaccine (0.5 ml volume per dose).

Systematic safety observation for all participants was conducted for 28 days post vaccination and blood specimens were collected on Day 0, 7, 14, 28, Month 3 and 6 after the boost for the immunogenicity assessment. A total of 113 participants at least 60 years of age were enrolled in group B and received a dose of CS-2034 for safety analysis. 1. Safety The analysis of the safety data within 28 days after the booster shows that heterologous CS-2034 booster has a favorable safety profile in people who had received three doses of COVID-19 inactivated vaccine previously.

The overall incidence of adverse events was mainly mild in severity. The incidence rate and severity of the adverse events of CS-2034 were significantly lower than those of the commercialized mRNA vaccines, according to literature reports. The safety profile of elderly participants is better than that of participants aged 18-59 years.

2. Immunogenicity The geometric mean titers (GMTs) of the live-virus neutralizing antibodies, on Day 28 post CS-2034 boost, were 877 against original strain, and 293 against Omicron BA.1 variant, which were 27 and 23 times as high as those in the inactivated vaccine group, respectively. The dynamics of cross-reactive neutralizing antibody against the current circulating Omicron BA.5 variant were measured, and found that the neutralizing antibody titer peaked (GMT = 407) at 7 days post CS-2034 boost, which was 29 times as high as that of homologous inactivated vaccine boost. The GMT of neutralizing antibody titer in elderly participants on Day 7 post CS-2034 boost was 296 against BA.5 variant, which was 23 times as high as that of homologous inactivated vaccine boost.