Slide 1: Top-Line Results of the Phase 2/3 booster Trial for COVID-19 Recombinant-based Vaccine, S-268019
Top-Line Results of the Phase 2/3 booster Trial for COVID-19 Recombinant-based Vaccine, S-268019 March 4, 2022
Slide 2: Forward-Looking Statements
Forward-Looking Statements • Forecast or target figures in this material are neither official forecasts of earnings and dividends nor guarantee of target, achievement and forecasts, but present the midterm strategies, goals and visions. Official earnings guidance should be referred to in the disclos
Slide 3: Agenda
Agenda 1. Vaccine classification 2. Overview of S-268019 3. Clinical trials of S-268019 Top-line results of the Phase 2/3 booster trial for S-268019 – Subject background – Immunogenicity – Neutralizing antibody titer against omicron variant – Safety – Summary 3
Slide 4: 1. Vaccine classification
for youl_/) 1. Vaccine classification @®SHIONOGI
Slide 5: Types of Vaccine Antigen Production Technology
Types of Vaccine Antigen Production Technology mRNA vaccine Recombinant （*COMIRNATY） protein vaccine （*Spikevax） （S-268019） Stabilization by conversion from RNA to DNA SARS-CoV-2 virus particle Inactivation of virus by heat/chemical treatment （RNA virus） DNA vaccine Inactivated vaccine （AG0302-COVID
Slide 6: Manufacturing Process of mRNA Vaccine
Manufacturing Process of mRNA Vaccine SARS-CoV-2 Genetic information virus of spike (S) protein mRNA Lipid component ＋ Extraction Transcription Formulation mRNA vaccine LNP* mRNA is encapsulated in LNP so that it is not degraded in the body * lipid nanoparticle 6
Slide 7: Manufacturing process of recombinant protein vaccine by BEVS
Manufacturing process of recombinant protein vaccine by BEVS* SARS-CoV-2 Genetic information virus of spike (S) protein Baculovirus** Insect cells Recombinant spike (S) protein*** ＋ Extraction Recombination Large-scale culture Purification Addition of Formulation adjuvant Vaccine ingredient manufact
Slide 8: Importance of Suitable Adjuvant Selection
Importance of Suitable Adjuvant Selection Safety Efficacy Supply Selection of suitable adjuvant Avoiding exacerbation of Enhance Conserving the amount symptoms by regulating immune response of antigen immune response 8
Slide 9: 2. Overview of S-268019
for you /) 2. Overview of S-268019 @®SHIONOGI
Slide 10: Overview of S-268019
Overview of S-268019 Antigen manufacturing technology BEVS* Product characteristics Full-length spike (S) protein + adjuvant Adjuvant A-910823 • Priming vaccine; 0.5 mL twice, usually every 4 weeks, intramuscular injection Expected dosage • Booster vaccine; 0.5 mL once, intramuscular injection Previ
Slide 11: Positioning of S-268019
Positioning of S-268019 Significance of domestic vaccine Environment surrounding booster vaccine • Domestic vaccines are extremely • Since the prevention of onset/the exacerbation prevention effect by the important from a national security priming vaccination decreases with the perspective passage o
Slide 12: 3. Clinical trials of S-268019
3. Clinical trials of S-268019
Slide 13: S-268019: List of Ongoing Clinical Trials
S-268019：List of Ongoing Clinical Trials Mar. 4, 2022 2021FY 2022FY 2023FY 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 Phase 1/2 trial*1 (New formulation: initiated Aug. 2021) Phase 2/3 trial*2 (safety, immunogenicity: initiated Oct. 2021) Phase 2/3 trial*3 (booster trial: initiat
Slide 14: S-268019: Overview of Ongoing Clinical Trials 1/2
S-268019：Overview of Ongoing Clinical Trials 1/2 Phase 1/2 trial Phase 2/3 trial Active control, neutralizing Placebo control, onset antibody titer trial prevention trial Priming/Booster Priming Priming Priming Priming Adults over 20 years old, elderly Subjects Healthy adults between the ages of ove
Slide 15: S-268019: Overview of Ongoing Clinical Trials 2/2
S-268019：Overview of Ongoing Clinical Trials 2/2 Phase 2/3 booster trial Phase 3 booster trial Priming/Booster Booster Booster Participant who have received 2 doses of SARS-CoV-2 Adults over 20 years old who at least 6 months have vaccine (Adults between the ages of 20 and 64: only passed after comp
Slide 16: Overview of the Phase 2/3 Booster Trial
Overview of the Phase 2/3 Booster Trial To evaluate if the immunogenicity of S-268019 demonstrates noninferiority compared to COMIRNATY and safety as a booster dose after Objectives completion of vaccination with two doses of COMIRNATY Subjects Adults over 20 years old who at least 6 months have pas
Slide 17: Top-Line Results (Interim Report) of the Phase 2/3 booster Trial
Top-Line Results (Interim Report) of the Phase 2/3 booster Trial for COVID-19 Recombinant protein Vaccine, S-268019 Tokyo Shinagawa Hospital Vice President and Director, Clinical trial Development & Research Center Masaharu Shinkai, MD, PhD COI Disclosure Information • Tokyo Shinagawa Hospital is en
Slide 18: Overview of the Phase 2/3 Booster Trial
Overview of the Phase 2/3 Booster Trial To evaluate if the immunogenicity of S-268019 demonstrates noninferiority compared to COMIRNATY and safety as a booster dose after Objectives completion of vaccination with two doses of COMIRNATY Subjects Adults over 20 years old who at least 6 months have pas
Slide 19: Key Demographics of Participants
Key Demographics of Participants Immunogenicity Subset S-268019 COMIRNATY N=103 N=102* Male 72 73 Sex Female 31 29 Min 21 21 Age (years) Max 59 60 Min 16.1kg/m2 16.4kg/m2 BMI Max 54.4kg/m2 41.8kg/m2 • Randomized：206 (S-268019: 103, COMIRNATY: 103) • Safety analysis population：206 (S-268019: 103, COM
Slide 20: Immunogenicity
Immunogenicity ＜ Statistical Hypothesis Testing ＞ If both the lower limit of the 95% confidence interval (CI) for the GMTR (S-268019 to COMIRNATY) of SARS-CoV-2 neutralizing antibody is greater than 0.67 and the lower limit of the 95% CI for the difference in seroresponse rate (S-268019 minus COMIRN
Slide 21: GMT of SARS-CoV-2 neutralizing antibody titer
GMT of SARS-CoV-2 neutralizing antibody titer GMT of SARS-CoV-2 neutralizing antibody on Day 29 (primary endpoints) 160 138.53 S-268019 COMIRNATY 128.14 126.42 140 S-268019 N=103 N=101 COMIRNATY 108.20 120 GMT 126.42 108.20 neutralizing antibody titer 100 80 95% confidence interval 109.76, 145.62 94
Slide 22: Seroresponse Rate of SARS-CoV-2 neutralizing antibody titer on Day 29
Seroresponse Rate of SARS-CoV-2 neutralizing antibody titer on Day 29 Seroresponse Rate on Day 29*1 (primary endpoints) *1 Seroresponse rate is defined as the proportion of participants with a ≥4-fold increase in post-vaccination antibody titer from baseline. S-268019 COMIRNATY N=103 N=101 Number of
Slide 23: Result of Primary Endpoints
Result of Primary Endpoints Interim results showed noninferiority of S-268019 to COMIRNATY in co-primary endpoints: GMT and seroresponse rate for neutralizing antibodies on day 29 In the interim report, this trial met its primary endpoint. 23
Slide 24: Immunologic Assays by Flow Cytometry (ICS-FCM)
Immunologic Assays by Flow Cytometry (ICS-FCM)* CD4+T Cell Baseline Day15 T-helper type 1 COMIRNATY S-268019 COMIRNATY S-268019 T-helper type 2 COMIRNATY S-268019 COMIRNATY S-268019 A strong bias toward the T-helper type 1 phenotype was noted * T-cell responses were assessed for a subgroup (n=30/gro
Slide 25: Neutralizing Antibody Titer against Pseudotyped Virus with SARS-CoV-2 Mutation Spike Protein
Neutralizing Antibody Titer against Pseudotyped Virus with SARS-CoV-2 Mutation Spike Protein* ** COMIRNATY S-268019 COMIRNATY S-268019 COMIRNATY S-268019 Day29 Serum samples from both vaccine groups neutralized pseudovirus variants including Omicron variants with similar potency as indicated by NT50
Slide 26: Safety
Safety
Slide 27: Treatment-related AEs
Treatment-related AEs (Treatment-related AEs will be defined as AEs considered to be “related” to the study intervention) ＜* Any systemic solicited TRAEs＞ ＜** Any local solicited TRAEs＞ • The following AEs were collected as solicited • The following AEs were collected as solicited local systemic AEs
Slide 28: Treatment-related AEs (TRAEs) (Incidents, 5% or more)
Treatment-related AEs (TRAEs) (Incidents, 5% or more) S-268019 N=103 COMIRNATY N=103 Participants with any Treatment-related AEs 99 (96.1%) 101 (98.1%) Headache 26 (25.2%) 43 (41.7%) Diarrhea 4 (3.9%) 6 (5.8%) Myalgia 42 (40.8%) 49 (47.6%) Arthralgia 8 (7.8%) 11 (10.7%) participants Vaccination site
Slide 29: Solicited Systemic AEs and Solicited Local TRAEs (Incidents)
Solicited Systemic AEs and Solicited Local TRAEs (Incidents) S-268019 N=103 COMIRNATY N=103 Participants with any 72 (69.9%) 81 (78.6%) systemic solicited TRAEs Fever 40 (38.8%) 61 (59.2%) Nausea/Vomiting 5 (4.9%) 5 (4.9%) Any systemic participants Diarrhea 4 (3.9%) 6 (5.8%) solicited ((%) of Headac
Slide 30: Solicited Systemic AEs and Solicited Local TRAEs (Severity)
Solicited Systemic AEs and Solicited Local TRAEs (Severity) • Grade 5：Death related to AE. • Grade 4：Life-threatening consequences; urgent intervention indicated. • Grade 3：Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indica
Slide 31: Solicited Systemic AEs and Solicited Local TRAEs (Timing of Onset)
Solicited Systemic AEs and Solicited Local TRAEs (Timing of Onset) ２６ S-268019 N=103 COMIRNATY N=103 1 36 (35.0%) 44 (42.7%) Timing of Onset (Day) 2 50 (48.5%) 61 (59.2%) 3 2 (1.9%) 2 (1.9%) participants Any systemic ((%) of 4 0 (0.0%) 0 (0.0%) solicited TRAEs participants) 5 0 (0.0%) 0 (0.0%) 6 0 (
Slide 32: Solicited Systemic AEs and Solicited Local TRAEs (Incidents, Severity) 1/3
Solicited Systemic AEs and Solicited Local TRAEs (Incidents, Severity) 1/3 S-268019 COMIRNATY S-268019 COMIRNATY N=103 N=103 N=103 N=103 Total 40 (38.8%) 61 (59.2%) 合計 4 (3.9%) 6 (5.8%) Grade 5 0 (0.0%) 0 (0.0%) Grade 5 0 (0.0%) 0 (0.0%) Fever Diarrhea Grade 4 0 (0.0%) 0 (0.0%) Grade 4 0 (0.0%) 0 (0
Slide 33: Solicited Systemic AEs and Solicited Local TRAEs (Incidents, Severity) 2/3
Solicited Systemic AEs and Solicited Local TRAEs (Incidents, Severity) 2/3 S-268019 COMIRNATY S-268019 COMIRNATY N=103 N=103 N=103 N=103 Total 45 (43.7%) 55 (53.4%) Total 8 (7.8%) 12 (11.7%) Grade 5 0 (0.0%) 0 (0.0%) Grade 5 0 (0.0%) 0 (0.0%) Fatigue Arthralgia Grade 4 0 (0.0%) 0 (0.0%) Grade 4 0 (0
Slide 34: Solicited Systemic AEs and Solicited Local TRAEs (Incidents, Severity) 3/3
Solicited Systemic AEs and Solicited Local TRAEs (Incidents, Severity) 3/3 Incidence (%) 59.2 60 53.4 S-268019 Grade 1 50 47.6 S-268019 Grade 2 41.7 43.7 40.8 S-268019 Grade 3 38.8 40 COMIRNATY Grade 1 COMIRNATY Grade 2 30 COMIRNATY Grade 3 25.2 20 11.7 10 5.8 7.8 6.8 4.9 4.9 3.9 3.9 S-268019 Fever
Slide 35: Solicited Local TRAEs (Incidents, Severity) 1/2
Solicited Local TRAEs (Incidents, Severity) 1/2 S-268019 COMIRNATY S-268019 COMIRNATY N=103 N=103 N=103 N=103 Total 68 (66.0%) 75 (72.8%) Total 0 (0.0%) 0 (0.0%) Grade 5 0 (0.0%) 0 (0.0%) Grade 5 0 (0.0%) 0 (0.0%) Pain Induration Grade 4 0 (0.0%) 0 (0.0%) Grade 4 0 (0.0%) 0 (0.0%) Severity Severity
Slide 36: Solicited Local TRAEs (Incidents, Severity) 2/2
Solicited Local TRAEs (Incidents, Severity) 2/2 Incidence (%) 80 72.8 70 66.0 S-268019 Grade 1 S-268019 Grade 2 60 COMIRNATY Grade 1 COMIRNATY Grade 2 50 40 30 20 10 6.8 8.7 1.0 1.0 0 S-268019 COMIRNATY Pain Erythema Swelling /Redness 36
Slide 37: Solicited Systemic AEs: Fever
Solicited Systemic AEs ：Fever ((%) of participants, Severity, Timing of Onset) (%) of participants, Severity S-268019 COMIRNATY Incidence (%) N=103 N=103 59.2 60 Total 40 (38.8%) 61 (59.2%) Grade 5 0 (0.0%) 0 (0.0%) S-268019 Grade 1 50 S-268019 Grade 2 Grade 4 0 (0.0%) 0 (0.0%) Severity S-268019 Gra
Slide 38: Solicited Systemic AEs: Headache
Solicited Systemic AEs ：Headache ((%) of participants, Severity, Timing of Onset) (%) of participants, Severity S-268019 COMIRNATY N=103 N=103 Incidence (%) Total 26 (25.2%) 43 (41.7%) 50 Grade 5 0 (0.0%) 0 (0.0%) 41.7 Severity Grade 4 0 (0.0%) 0 (0.0%) S-268019 Grade 1 40 S-268019 Grade 2 Grade 3 0
Slide 39: Solicited Systemic AEs: Fatigue
Solicited Systemic AEs ：Fatigue ((%) of participants, Severity, Timing of Onset) (%) of participants, S-268019 COMIRNATY Severity N=103 N=103 Incidence (%) 53.4 Total 45 (43.7%) 55 (53.4%) 50 Grade 5 0 (0.0%) 0 (0.0%) 43.7 S-268019 Grade 1 S-268019 Grade 2 Grade 4 0 (0.0%) 0 (0.0%) Severity 40 COMIR
Slide 40: Summary
Summary Immunogenicity − In the interim report, this trial met its primary endpoint. > The results showed the noninferiority of S-268019 to COMIRNATY. Safety − There were no treatment-related serious AEs, deaths, grade 4-5 solicited TRAEs, or AEs of special interest in both group. − The most fre
Slide 41: End of slides
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