A Novel and Safe SmartCap® SC101 to Develop COVID-19 mRNA Vaccine STP2104 Inducing Potent Immune Responses in Humans

Rachel Kim¹Tae-Gi Uhm¹Jisu Kim¹Dayeon Woo¹Uk-Il Kim¹Xue Meng¹Byounggu Yang¹Jonghyeon Kim¹Sunkyung Yoon²Joo-Young Lee¹Byungkyun Kim¹Dongheon Cho¹Duckho Chang¹Young-Hwan Cho¹Kanghyun Choi¹WonSeok Gwak²Hoon-Woo Lee¹Jieun Bang¹Elizabeth Hellstrӧm³Byoungguk Kim²Kyungjin Kim^1*Joo-Sung Yang^1*

• ¹R&D Center, ST Pharm Co., Ltd., Seoul, Republic of Korea
• ²Division of Clinical Research for vaccine, Center for Vaccine Research, National Institute of Infectious Diseases, Korea National Institute of Health, Cheongju-si, Republic of Korea
• ³Be Part Research (PTY) Ltd., Paarl, South Africa

We have developed a 5'-Capping Library Screening (CLS) method using over 30 different novel cap analogues. The optimal 5'-cap for COVID-19 mRNA vaccine STP2104 was selected and applied. This is the first report to describe the proven safety of the novel cap analogue, SmartCap ® SC101, in humans and emphasize the importance of cap selection. STP2104 results in humans demonstrated safety, tolerability, and strong immune responses. After confirming its safety by GLP toxicity study, STP2104 was administered intramuscularly as a two-dose vaccine, separated by 28 days, in COVID-19 naïve, healthy adult volunteers. In this multicenter, open-label, dose escalation, phase I study with 30 participants (18 to 55 years of age), 15 individuals each were in the low (25 μg) and high 50 μg dose cohorts. The primary endpoints were to evaluate the safety and immunogenicity in all cohorts. During the reporting period of the trial, no serious adverse events were reported. Plaque reduction neutralization test depicted at least 21-fold increase in NAb titers from both cohorts when comparing pre-vaccination to 4-week post second vaccination. These safety and NAb titer interim results support the efficiency and safety of SC101, and STP2104 mRNA vaccine, including how STP2104 effectively induces NAb titers against SARS-CoV-2.