Shionogi : Notice Regarding the Initiation of an Active Control Neutralizing Antibody Comparative Clinical Trial for COVID-19 Recombinant Protein-based Vaccine

Press Release

Notice Regarding the Initiation of an Active Control Neutralizing Antibody

Comparative Clinical Trial

for COVID-19 Recombinant Protein-based Vaccine, S-268019 in Japan

Osaka, Japan, January 17, 2022 - Shionogi & Co., Ltd. (Head Office: Osaka, Japan; President and

CEO: Isao Teshirogi, Ph.D.; hereafter "Shionogi") today announced that it has initiated a Japanese Phase 3 active control neutralizing antibody comparative clinical trial of a prophylactic vaccine candidate for COVID-19 (code No. S-268019), caused by the novel coronavirus (SARS-CoV-2) infection.

Past development of COVID-19vaccines has usually entailed large-scaleclinical trials to evaluate the onset prevention effect. However, as effective vaccines have become broadly distributed and more and more of the population has been vaccinated, it has become difficult to carry out onset prevention studies. At the same time, substantial demand remains for additional, and even initial, vaccine doses globally; therefore, it is necessary to develop safe and effective new vaccines. Under these circumstances, to progress the development of a new vaccine against COVID-19,the neutralizing antibody titer after vaccination can be used as a substitute index for the onset prevention effect. After discussions at the International Coalition of Medicines Regulatory Authorities (ICMRA), neutralizing antibody titer comparison trials to evaluate a new vaccine in comparison to approved vaccines has been recognized as a viable evaluation method.1

The phase 3 clinical trial that started in Japan is a neutralizing antibody titer comparison study using an approved vaccine as a control. For adults and the elderly, the study compares the neutralizing antibody titer against the SARS-CoV-2 28 days after the second inoculation of S-268019 or the control vaccine (jRCT No.:2051210151). We will continue to consult closely with the Ministry of Health, Labor and Welfare, Pharmaceuticals and Medical Devices Agency (PMDA) and other organizations regarding applications for approval based on the progess and results of the ongoing clinical trial. 2, 3, 4, 5

Shionogi's key focus and commitment is to protect people worldwide from the threat of infectious diseases. We are working toward total care for infectious diseases through awareness building, epidemiological surveillance, prevention, diagnosis, and addressing exacerbations, as well as treating the infection itself. As SARS-CoV-2 continues to have a major impact on people's lives and represents a global threat, we will seek to contribute to re-establishing the safety and security of society by developing, delivering, and producing a vaccine for COVID-19 in Japan. We will keep all stakeholders informed regarding the progress of our efforts.

Forward-Looking Statements

This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties, which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions, such as general industry and market conditions and changes in interest and currency exchange rates. These risks and uncertainties particularly apply with respect to product-relatedforward-looking statements. Product risks and uncertainties include but are not limited to completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also, for existing products, there are manufacturing and marketing risks, which include

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but are not limited to inability to build production capacity to meet demand, lack of availability of raw materials, and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events, or otherwise.

【About a Japanese Phase 1/2 clinical trial2】

The Phase 1/2 clinical trial is double-blind and placebo-controlled study to evaluate safety, tolerability and immunogenicity of two doses of the vaccine. 60 adults are enrolled in the trial. For more information about this clinical trial, please refer to jRCT No.:2031210269. Subject registration for this trial has been completed. In the evaluation up to 28 days of two doses of the vaccine, confirmed tolerability and safety, neutralizing antibody titer equal to or higher than that of convalescent serum.

【About a Japanese Phase 2/3 clinical trial3】

The Phase 2/3 clinical trial is a open-label study to evaluate safety, tolerability and immunogenicity of s-268019 in 3,100 adults and elderly people. For more information about this clinical trial, please refer to jRCT No.:2031210383. Subject registration for this trial has been completed.

【About Phase 3 additional dose clinical trial4】

This clinical trial is a randomized, active controlled, double-blind trial. In this trial, the efficacy and safety of an additional dose of Comirnaty or S-268019 in 200 adults, 6 months or more after receiving a primary series of Comirnaty, will be compared.. For more information about this clinical trial, please refer to jRCT No.:2031210470. Subject registration for this trial has been completed.

【About Phase 3 active control neutralizing antibody comparative clinical trial】

This clinical trial is a double-blind randomized active controlled trial to evaluate a neutralizing antibody titer after the primary series of Vaxzevria or S-268019 in 1,000 adults and the elderly people.For more information about this clinical trial, please refer to jRCT No.: 2051210151.

【About Global Phase 3 placebo-controlled onset prevention clinical trial5】

This clinical trial is a randomized, placebo-controlled,double-blind trial to evaluate the onset prevention effect for COVID-19 after primary series of S-268019 compared with placebo. Approximately 50,000 adults and the elderly people will be enrolled and randomly assigned 2:1 to S-268019 and placebo. This clinical trial adopted crossover assignment, then all participant can get an opportunity to access active control. Currently, we are proceeding with subject registration in Vietnam, the first country in which this trial have been approved.

In any clinical trial, subjects can decline to participate in the trial at any time during the trial period if they want.

Phase 1/2 Clinical Trial was supported by Japan Agency for Medical Research and Development (AMED).

Our efforts against COVID-19 are updated on our website, as needed. A considerable amount of valuable information on COVID-19 from other websites is also summarized on this page, so please use it for reference: SHIONOGI website

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For Further Information:

SHIONOGI Website Inquiry Form :https://www.shionogi.com/global/en/contact.html

References

1. ICMRA COVID-19 Vaccine development: Future steps Workshop
2. Press release on December 7, 2021
   Shionogi Presents Japanese Phase 1/2 Clinical Trial Results of COVID-19 Recombinant Protein-based Vaccine at Conference
3. Press release on October 21, 2021
   Notice Regarding the Progress of Phase 2/3 Clinical Trial for New Formulation of COVID-19 Recombinant Protein-based Vaccine
4. Press release on December 3, 2021
   Notice Regarding an Initiation of a Additional Dose Clinical Trial for COVID-19Recombinant-based Vaccine
5. Press release on December 27, 2021
   Notice Regarding the Initiation of a Global Phase 3 Clinical Trial for COVID-19 Recombinant Protein-based Vaccine, S-268019

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