Slide 1: Phase 2b part of S-217622, a novel 3C-like protease inhibitor
Phase 2b part of S-217622, a novel 3C-like protease inhibitor as once daily oral treatment for SARS-CoV-2 infection in Japan and South Korea Norio Ohmagari1, Hiroshi Yotsuyanagi2, Yohei Doi3, 4, Takuhiro Sonoyama5, Takumi Imamura5, Takao Sanaki5, Keiko Baba5, Genki Ichihashi5, Takahiro Fukuhara5, Yo
Slide 2: Transparency declaration
Transparency declaration • I am a member of S-217622 Advisory Board.
Slide 3: 3CLpro is a key enzyme in the viral replication
3CLpro is a key enzyme in the viral replication Viral attachment ACE2 TMPRSS2 Viral entry Exocytosis ERGIC 3CLpro inhibitor Uncoating S-217622 Translation Genome +ss genomic RNA Virion assembly pp1a replication N N pp1ab Transcription Translation S E M Structural proteins N N N sub genomic mRNA O Po
Slide 4: Phase 2b part outline
Phase 2b part outline Mild/moderate symptoms Subjects SARS-CoV-2-infected subjects Clinical trial Multicenter, randomized, Inclusion criteria design placebo-controlled, double-blinded study • 12 to 70 years of age, at the time of signing the Endpoints Virologic response, clinical symptom, safety inf
Slide 5: Patient disposition
Patient disposition Screening failure (n=9) 437 patients with informed consent screened • Withdrawal by subject (n=4) • Protocol deviation (n=3) • Lost to follow-up (n=1) • Other (n=1) Safety Analysis 142 randomized to 143 randomized to 143 randomized to S-217622 125 mg S-217622 250 mg placebo Infor
Slide 6: Patient demographics and baseline characteristics
Patient demographics and baseline characteristics S-217622 125 mg S-217622 250 mg Placebo ITT1 Population (n=114), n (%) (n=116), n (%) (n=111), n (%) Sex Male 61 (53.5) 66 (56.9) 72 (64.9) Mean (SD) 35.6 (13.5) 35.3 (13.1) 37.3 (12.6) ≥12 to <18 4 (3.5) 2 (1.7) 2 (1.8) Age ≥18 to <65 109 (95.6) 112
Slide 7: Patient demographics and baseline characteristics (cont'd)
Patient demographics and baseline characteristics (cont’d) S-217622 125 mg S-217622 250 mg Placebo (n=114), n (%) (n=116), n (%) (n=111), n (%) COVID-19 Respiratory Stuffy or runny nose 29 (25.4) 34 (29.3) 26 (23.4) symptoms symptoms Sore throat 65 (57.0) 63 (54.3) 54 (48.6) Shortness of breath 8 (7
Slide 8: Primary endpoint: Viral titer change from baseline by Day 4 (ITT1)
Primary endpoint: Viral titer change from baseline by Day 4 (ITT1) S-217622 S-217622 Placebo Statistics 125 mg 250 mg (n=111) (n=114) (n=116) n 106 112 107 Mean (SD) –1.69 (0.84) –1.43 (0.83) –1.06 (0.99) LS mean (SE) by –1.49 (0.04) –1.49 (0.04) –1.08 (0.04) ANCOVAa Difference in LS means –0.41 (0.
Slide 9: Secondary endpoint: change from baseline in viral titer by time (ITT1)
Secondary endpoint: change from baseline in viral titer by time (ITT1) Observed value in SARS-CoV-2 viral titer Change from baseline in SARS-CoV-2 viral titer 4 1 Placebo S-217622 125 mg Placebo S-217622 125 mg S-217622 250 mg S-217622 250 mg 3 0 (log10(TCID50/mL)) (log10(TCID50 )/mL) * * Viral tite
Slide 10: Secondary endpoint: change from baseline in viral RNA by time (ITT1)
Secondary endpoint: change from baseline in viral RNA by time (ITT1) Observed value in SARS-CoV-2 viral RNA Change from baseline in SARS-CoV-2 viral RNA 8 1 Placebo S-217622 125 mg Placebo S-217622 125 mg 7 * 0 * S-217622 250 mg S-217622 250 mg 6 -1 * (log10(copies /mL)) (log10(copies /mL)) * Viral
Slide 11: Secondary endpoint: time to the first negative viral titer (ITT1)
Secondary endpoint: time to the first negative viral titer (ITT1) 100 S-217622 S-217622 Placebo 125 mg 250 mg (n=108) (n=111) (n=113) Proportion of first negative 80 SARS-CoV-2 viral titer (%) Median 51.3 62.1 91.9 60 50 [95% CI] [44.1, 61.8] [43.7, 66.5] [84.0, 109.9] 40 Difference –40.6 –29.8 Cens
Slide 12: Primary endpoint: Change from baseline in COVID-19 symptoms Total Score (ITT)
Primary endpoint: Change from baseline in 12 COVID-19 symptoms Total Score (ITT) S-217622, S-217622, Placebo Statistics 125 mg 250 mg (n=111) (n=114) (n=116) n 109 113 110 Mean (SD) –5.95 (4.02) –5.42 (3.70) –4.92 (3.25) LS mean (SE) by ANCOVAa –5.37 (0.24) –5.17 (0.23) –5.12 (0.24) Difference in LS
Slide 13: Change in COVID-19 symptoms Total Score by time (ITT)
Change in 12 COVID-19 symptoms Total Score by time (ITT) Observed value in total score of Change from baseline in total score of COVID-19 symptoms (mean) COVID-19 symptoms (mean) 12 2 Placebo S-217622 125 mg Placebo S-217622 125 mg S-217622 250 mg S-217622 250 mg 10 0 8 -2 6 -4 4 -6 2 -8 0 -10 0 12
Slide 14: Change in Subtotal Score of COVID-19 symptoms (ITT)
Change in Subtotal Score of COVID-19 symptoms (ITT) Respiratory Symptoms Systemic Symptoms Digestive Symptoms (mean) (mean) (mean) Placebo S-217622 125 mg S-217622 250 mg 1 1 1 0 0 -1 -1 -2 -2 0 -3 -3 -4 -4 -5 -5 -6 -1 0 12 24 36 48 60 72 84 96 108 120 0 12 24 36 48 60 72 84 96 108 120 0 12 24 36 48
Slide 15: Change in Subtotal Score of COVID-19 symptoms (ITT)
Change in Subtotal Score of COVID-19 symptoms (ITT) Post hoc analysis Main clinical symptoms Acute symptoms Respiratory symptoms + feverish (mean) (mean) (mean) Placebo S-217622 125 mg S-217622 250 mg 1 1 1 0 0 0 -1 -1 -1 -2 -2 -2 -3 -3 -3 -4 -4 -4 -5 -5 -5 -6 0 12 24 36 48 60 72 84 96 108 120 0 12
Slide 16: Safety
Safety S-217622 S-217622 Placebo 125 mg 250 mg (n=141) (n=140) (n=140) n (%) n (%) n (%) Number of participants with any TEAEs 48 (34.3) 60 (42.9) 44 (31.2) TEAE reported in ≥2% of patients in any group Dyslipidemia 0 3 (2.1) 0 Headache 3 (2.1) 3 (2.1) 0 Diarrhea 2 (1.4) 3 (2.1) 1 (0.7) Abdominal pa
Slide 17: Summary and Conclusions
Summary and Conclusions • Phase 2b was conducted to assess S-217622 efficacy and safety in patients with mild/moderate COVID-19 symptoms during the Omicron epidemic • S-217622 demonstrated significant reduction and rapid clearance of infectious SARS-CoV-2 • No clear difference was observed in total
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Slide 19: Changes in HDL cholesterol, Triglycerides, Total bilirubin and Iron in Blood
Changes in HDL cholesterol, Triglycerides, Total bilirubin and Iron in Blood HDL cholesterol (mmol/L) Triglycerides (mmol/L) 3 5 4 2 3 2 1 1 0 0 -1 Baseline Day 6 Day 14 Day 28 Baseline Day 6 Day 14 Day 28 Analysis Visit Analysis Visit Placebo Total bilirubin (µmol/L) Iron (µmol/L) S-217622 125 mg 3
Slide 20: Secondary endpoint: proportion of patients with a positive viral titer (ITT1)
Secondary endpoint: proportion of patients with a positive viral titer (ITT1) 100 Placebo S-217622 125 mg S-217622 250 mg 80 Proportion (%) 60 40 20 * * * * 0 (111/111)(113/113)(115/115) (91/111) (81/112) (75/113) (54/108) (2/107) (6/112) (17/108) (2/111) (1/112) (1/105) (4/109) (0/106) (1/102) (0/1