Slide 1: Treatment for >12 Weeks with the CAM ALG-000184 and Entecavir Dose Dependently Reduces HBsAg
Treatment for >12 Weeks with the Capsid Assembly Modulator (CAM) ALG-000184 and Entecavir (ETV) Dose Dependently Reduces HBsAg in HBeAg+ Subjects with Chronic Hepatitis B (CHB) McClure Matthew [1], Hou Jinlin [2], Ding Yanhua [3], Niu Junqi [3], Liang Xie’er [2], Le Kha [1], Lin Tse-I [4], Wu Min [5
Slide 2: Disclosures for Ed Gane
Disclosures for Ed Gane • I have been an advisor and/or speaker for: AbbVie, Abbott Diagnostics, Aligos, Arbutus, Arrowhead, Assembly, Dicerna, Gilead Sciences, Glaxo Smith Kline, Intellia, Janssen, Merck, Novartis, Precision Biosciences, Genentech-Roche, Tune, Vaccitech, Vir Bio and Virion Therapeu
Slide 3: ALG-000184 Background
ALG-000184 Background • Capsid assembly modulators which produce empty viral particles (CAM-E) have been extensively studied for treating chronic hepatitis B (CHB) • CAM-E drugs have 2 antiviral mechanisms of action: – Inhibition of hepatitis B virus pregenomic RNA (HBV pgRNA) encapsidation leading
Slide 4: ALG-000184-201 Part 4 Cohorts
ALG-000184-201 Part 4 Cohorts Cohort 1 Randomize N=8 Follow-up (+ ETV) HBeAg (+) 3 active:1 placebo ALG-000184 100 mg + ETV x 24 weeks x 8 weeks N=11 (fully enrolled, Placebo + ETV N=2 ALG-000184 + ETV Follow-up (+ ETV) study complete) x 12 weeks x 12 weeks x 8 weeks Cohort 2 Randomize N=8 Follow-up
Slide 5: ALG-000184-201 Part 4 Key Study Entry Criteria
ALG-000184-201 Part 4 Key Study Entry Criteria Entry Criterion Cohort 1 Cohort 2 Not on treatment Treatment status Treatment naive (treatment naïve or treated in past) ALT/AST ≤1.2 x ULN ≤5 x ULN HBV DNA >107 IU/mL >2000 IU/mL HBsAg >100 IU/mL ALT/AST = alanine or aspartate aminotransferase; ULN = u
Slide 6: Baseline Characteristics – Typical for HBeAg+ Population
ALG-000184-201 Part 4 Baseline Characteristics – Typical for HBeAg+ Population Cohort 1 Cohort 2 (100 mg ALG-000184 + ETV and (300 mg ALG-000184 + ETV and Placebo + ETV) Placebo + ETV) N N=11 N=15 Age, years, mean (SEM) 35.1 (2.1) 31.4 (3.3) Female, N (%) 7 (64) 7 (46.7) Asian, N (%) 11 (100) 15(100
Slide 7: ALG-000184-201 Part 4 Safety
ALG-000184-201 Part 4 Safety Cohort 1 Cohort 2 100 mg ALG-000184 + ETV or 300 mg ALG-000184 + ETV or Placebo + ETV Placebo + ETV N 11 15 Serious Adverse Event (SAE) 0 0 Treatment Emergent Adverse Event (TEAE) 0 0 leading to study drug discontinuation Transaminase elevations, oropharyngeal pain, Most
Slide 8: HBV DNA Declines In Subjects Receiving ALG-000184 x ≥12 Weeks
Part 4 Cohort 1 (100 mg ALG-00184 + ETV x 24 weeks) HBV DNA Declines In Subjects Receiving ALG-000184 x ≥12 Weeks N=4 dosed with 100 mg ALG-000184 + ETV x 24 weeks At Week 24, all subjects had HBV DNA of >6 log10 IU/mL Add on ALG-000184 : additional ~2 log10 IU/mL HBV DNA decline vs. ETV Mean + SEM
Slide 9: HBsAg Declines In Subjects Receiving ALG-000184 x ≥12 Weeks
Part 4 Cohort 1 (100 mg ALG-00184 + ETV x 24 weeks) HBsAg Declines In Subjects Receiving ALG-000184 x ≥12 Weeks At week 24, 3 of 4 subjects had HBsAg decline of >0.4 log10 IU/mL Maximum HBsAg decline of ~0.7 log10 IU/mL Add on ALG-000184: downward HBsAg trend seen after switch 8
Slide 10: HBV DNA Declines In Subjects Receiving ALG-000184 x ≥12 Weeks
Part 4 Cohort 2 (300 mg ALG-00184 + ETV x 48 weeks) HBV DNA Declines In Subjects Receiving ALG-000184 x ≥12 Weeks N=7 and N=5 dosed with 300 mg ALG-000184 + ETV x ≥12 weeks and ≥24 weeks, respectively At Week 24, all subjects had HBV DNA decline of ≥6 log10 IU/mL, 1 subject was undetectable Mean + S
Slide 11: HBsAg Declines In Subjects Receiving ALG-000184 x ≥12 Weeks
Part 4 Cohort 2 (300 mg ALG-00184 + ETV x 48 weeks) HBsAg Declines In Subjects Receiving ALG-000184 x ≥12 Weeks Non-responder (N=1) Responder (N=6) After 12 weeks, 6 of 7 subjects had HBsAg decline of ≥0.4 log10 IU/mL After 24 weeks, 4 of 5 subjects had HBsAg decline of ≥1 log10 IU/mL Maximum observ
Slide 12: Change in HBsAg vs. PK (Week 24)
ALG-000184-201 Part 4 Change in HBsAg vs. PK (Week 24) AUC Ctrough Non-responder 3x HBsAg EC90 3x HBsAg EC90 (Liver) (Liver) HBsAg declines appear to be correlated to plasma ALG-001075 PK (both AUC and Ctrough) BID dosing (which raises Ctrough) might further enhance HBsAg lowering – cohort planned 1
Slide 13: ALG-000184 Conclusions
ALG-000184 Conclusions • When combined with ETV for up to 28 weeks in HBeAg+ subjects not on treatment, ALG-000184 demonstrated: – Favorable safety profile – Superior reductions in HBV DNA compared to ETV alone – Substantial reductions in HBsAg (up to 1.65 log10 IU/mL) › >1 log10 IU/mL reduction in
Slide 14: Acknowledgments
Acknowledgments • The authors wish to thank the following for their contributions: – The subjects and their families for their participation – The two clinical investigational study teams › Nanfang Hospital Infection Disease Department › Jilin University the 1st Hospital Phase 1 Unit – Aligos intern