Shionogi will work with Chiba University Hospital and HanaVax inc. to develop a nasal vaccine for COVID-19 using a cationic nanogel delivery system. Nasal vaccines are expected not only to prevent the onset and aggravation of pathogen infection, but also to prevent pathogen infection itself by efficiently inducing mucosal immunity in the nasal cavity and throat. It also has the advantage that it does not have the pain of an injectable vaccine and does not necessarily require administration by a sophisticated medical system or medical staff. Currently, we are conducting research with the aim of entering clinical trial in FY2022.

Shionogi discovered a small molecule oral antiviral drug (S-217622) which is 3CL protease inhibiter that selectively inhibits the enzyme essential for virus through vigorous collaborative research with the Hokkaido University Research Center for Zoonosis Control. S-217622 has demonstrated that the viral load is rapidly and significantly reduced in non-clinical trials using SARS-CoV-2 infected animals. According to non-clinical trials, Shionogi confirmed high antiviral activity against the Omicron variant similar to other existing variants.

In a Japanese Phase1 clinical trial started in July 2021, we confirmed tolerability, safety and pharmacokinetics. Based on the result in Phase 1, a Japanese phase 2/3 clinical trial was started on September 27, 2021. The phase 2/3 clinical trial will evaluate the efficacy and safety of oral administration of this drug once daily for 5 days in mild, moderate, or asymptomatic COVID-19 patients, in comparison with placebo.

The latest results on Phase 2a/2b Part of the Phase 2/3 clinical trial were presented at the 32^nd European Congress of Clinical Microbiology & Infectious Diseases (April 23-26, 2022). The results have been submitted to PMDA, and the Phase 3 Part for mild / moderate patients and the Phase 2b / 3 Part for SARS-CoV-2 infected individuals with only asymptomatic / mild symptoms is ongoing. Registration is proceeding smoothly not only in Japan but also in South Korea and Vietnam.

As expressed in the related notifications^{1, 2}, Shionogi has been consulting with PMDA from the early stages of S-217622 development. We have already submitted data on non-clinical trials, manufacturing / CMC³ and some clinical trials. Based on the results of the main evaluation analysis of Phase 2b Part, on February 25, 2022, we submitted a manufacturing and marketing approval application requesting the application of the conditional approval system in Japan. We will continue to accelerate the evaluation of Phase 2/3 clinical trials with the aim of providing S-217622 as soon as possible, and will promptly submit the results to PMDA as soon as they are available.  

Regarding the supply system, we are making good progress toward the domestic supply, because we were preparing in parallel with the clinical trials. In the development of this therapeutic drug, we are giving top priority to the supply to Japan, and on March 25, 2022, we signed a basic agreement with the Ministry of Health, Labor and Welfare for the domestic supply of S-217622.

For global development, FDA⁴ has approved conducting a global Phase 3 trial as part of the ACTIV-2 program. ACTIV-2, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), is one of the public-private partnership programs "ACTIV⁵". It was set up to create a coordinated research strategy that prioritizes and speeds development of the most promising therapeutic agents and vaccines for COVID-19. With NIAID funding, The AIDS Clinical Trials Group⁶ and we will work together to conduct clinical trials.

Furthermore, regarding global provision, we are continuing to negotiate with multiple companies regarding partnering with a view to supporting the construction of a sales system.

Furthermore, we are continuing our discovery efforts, using various modalities, including small molecules, peptides, and antibodies. Among them, we succeeded in creating COVID-19 candidates using PDPS (Peptide Discovery Platform System). We will strengthen the preparations for next pandemics, not only for the novel coronavirus, but also for other coronaviruses. 

1. Handling of drugs for approval examination for COVID-19

2. Handling of drugs for approval examination for COVID-19 (ver.2)

3. CMC：Chemistry Manufacturing and Control

4. FDA：Food and Drug Administration

5. ACTIV：Accelerating COVID-19 Therapeutic Interventions and Vaccines

6. The largest global HIV research network that expanded its focus to include evaluating outpatient treatments for COVID-19

Shionogi has concluded a joint sales agreement with Towns Co., Ltd. for novel coronavirus (SARS-CoV-2) antigen test kit products, and from November 29^th2021, Shionogi started joint sales of "Immunoace® SARS-CoV-2 II". This kit can easily obtain results in a short time of about 15 minutes with a nasopharyngeal swab or a nasal swab. In addition, based on this agreement, joint sales of "Immunoace® SARS-CoV-2 Saliva", which uses saliva as a sample, have started on April 25, 2022.

Shionogi Healthcare's Online Shop has started offering a PCR test service that enables home-based tests, online medical examinations, and cooperation with health centers in November 29th. It is also compatible with mutant viruses, and it is possible to issue a publicly valid negative certificate. Shionogi will work towards total care for infectious diseases.

On May 24, 2021, Shionogi and Lumira Diagnostics Japan Co., Ltd. have started joint sales of SARS-CoV-2 antigen test agent "Lumira SARS-CoV-2 Ag test strip" and "Lumira measuring device". This test agent and measuring device are also sold in the United States, Europe, etc. The LumiraDx SARS-CoV-2 Ag Test combines high-sensitivity results comparable to those from the PCR with speed and efficiency (results in less than 12 minutes) using samples from a nasopharyngeal swab or nasal swab.

“HISCL® TARC Assay Kit", a Th2 chemokine (TARC) kit, is marketed as an auxiliary for assessment of aggravation risk in patients who have tested positive for SARS-CoV-2. The kit was developed jointly by Shionogi and Sysmex Corporation.

Through the latest clinical research, the National Center for Global Health and Medicine has identified TARC, which is a useful biomarker for predicting the aggravation of COVID-19 patients from an early stage with a single measurement. It has been confirmed that the serum level of TARC remain low value in patients with severe symptoms of COVID-19 from early onset to aggravation. The test kit is expected to identify patients with a high risk of aggravation from the early stage of COVID-19 onset and it will be possible to follow up them intensively. It means helping to solve medical problems. It would contribute to effective utilization of medical resources, relief of medical system overwhelmed by increasing number of people receiving medical treatment, and reduce the risk of future medical collapse. After the launch, we are also engaged in clinical research to build evidence.

Based on our license agreement for a new rapid diagnostic method for viral infections, including the novel coronavirus, with Nihon University, Gunma University, and Tokyo Medical University, Shionogi is pursuing the development of a new rapid diagnostic method for COVID-19, using an innovative nucleic acid amplification technique, the SATIC (signal amplification by ternary initiation complexes) method. On the other hand, in consideration of the balance of other test methods such as PCR and antigen test, we have stopped the efforts to commercialize the SATIC method for COVID-19. Basic research will continue in academia, and we will continue to hold the license right for the SATIC method.

Shionogi has concluded a license agreement with BioAge Labs, Inc. (hereafter "BioAge") to develop asapiprant (S-555739) to control the aggravation of COVID-19. Asapiprant is a DP1 receptor antagonist discovered by Shionogi. In a clinical trial conducted by BioAge, administration of asapiprant in aged mice infected with SARS-CoV-2 significantly decreased the mortality rate and viral load in the lungs. Several non-clinical studies and clinical trials in over 2,400 subjects have shown that asapiprant has high affinity and selectivity for the DP1 receptor and is well tolerated and safe.

Based on the favorable results of non-clinical studies, BioAge has initiated a Phase 2 clinical trial in older patients with COVID-19. Shionogi is supporting BioAge's rapid initiation of the clinical trial by supplying investigational drugs and cooperating with the IND application to the US FDA. 

In January 2022, Shionogi established AdvanSentinel Co., a joint venture with Shimadzu Corporation for the purpose of public health risk assessment such as wastewater surveillance. AdvanSentinel aims to build an All-Japan system to detect the next pandemic and other public health risks, not only COVID-19. This will be accomplished by combining the wastewater monitoring networks² built by each company, and by developing new analytical methods and technologies, leveraging the analytical science strengths of Shionogi and the environmental molecular measurement technology expertise of Shimadzu.

The wastewater epidemiological surveillance service is a service based on wastewater epidemiology that regularly monitors the concentration of viruses contained in wastewater and investigates the infection status in the target area.

This service uses a highly sensitive detection system (patent pending) that we have developed jointly with Hokkaido University. By measuring the traces of the virus in wastewater, it is possible to assess, in an unbiased manner, the prevalence of SARS-CoV-2 infections in a community.

Shionogi launched mutational analysis services to detect the development and spread of variants in the target area, in addition to quantitative measurement service of inflow to municipal sewage treatment plants. This technology can detect not only existing variants, such as the Alpha and Delta, but also the Omicron variant, which was designated as the most alarming ‘variant of concern²’ by the World Health Organization (WHO) on November 26, 2021.

Shionogi has agreed with Osaka and Tokyo prefecture to dispatch employees to the health centers in areas where the burden on the medical system and health centers had increased in order to deal with the rapidly increasing number of infected people, to support COVID-19 epidemic prevention activities. They assisted public health nurses in mainly peripheral work including data entry of patient outbreak information, preparation and sending of documents such as work restriction notifications and inspection requests, and logistics support for epidemiological investigations such as telephone interviews.

【Support results】 

Dispatch period : February 22nd to March 31st, 2021
Dispatched employees :
         18 people were dispatched to 9 health centers in Osaka Prefecture
          4 people were dispatched to 4 health centers in Tokyo

Dispatch period : April 15th to April 28th, 2021
Dispatched employees :
         30 people were dispatched to 12 health centers in Osaka Prefecture

Dispatch period : August 18th to August 31st, 2021
Dispatched employees :
         24people were dispatched to 9health centers in Osaka Prefecture