Slide 1: Imdusiran (AB-729) every 8 weeks for 24 weeks followed by VTP-300
Imdusiran (AB-729) administered every 8 weeks for 24 weeks followed by the immunotherapeutic VTP-300 maintains lower HBV surface antigen levels in NA-suppressed CHB subjects than 24 weeks of imdusiran alone Kosh Agarwal1, Man-Fung Yuen2, Stuart Roberts3, Gin-Ho Lo4, Chao-Wei Hsu5, Wan-Long Chuang6,
Slide 2: Disclosures – Dr. Kosh Agarwal
Disclosures – Dr. Kosh Agarwal Consultancy: Aligos, ASC Therapeutics, Bluejay Therapeutics, DrugFarm, Gilead, GSK, Grifols, Janssen, PrecisionBio, Roche, Surrozen, Tune, Vir Grants: Gilead, GSK, Abbott 2
Slide 3: Background
Background Current approved therapies for chronic hepatitis B (CHB) slow or prevent the development of HBV-related liver complications, but do not typically lead to functional cure (HBV DNA suppression and HBV surface antigen [HBsAg] loss, with or without HBsAb seroconversion at least 6 months off a
Slide 4: Study Rationale
Study Rationale Preclinical data in the AAV-HBV mouse model supports lowering HBsAg with an siRNA then following with a therapeutic vaccine to potentiate HBsAg loss and T cell responses1 Imdusiran for 24 weeks (to reduce HBsAg to low levels), followed by VTP-300 (to enhance HBV-specific T cell respo
Slide 5: Study overview: IM-PROVE II (AB-729-202)
Study overview: IM-PROVE II (AB-729-202) IM-PROVE II is a randomized, placebo-controlled, multicenter Phase 2a proof-of-concept study (ACTRN12622000317796) Primary Objective: To evaluate the safety and reactogenicity of the combination of imdusiran followed by VTP-300 or placebo injection Week 48/EO
Slide 6: Demographics: Baseline characteristics were comparable between groups
Demographics: Baseline characteristics were comparable between groups Group A Group B Total Parameter VTP-300 (N=20) Placebo (N=20) (N=40) Age, mean (SD) 52.2 (6.45) 44.3 (8.33) 48.2 (8.37) Median baseline HBsAg was Males, n (%) 14 (70) 14 (70) 28 (70.0) over 800 IU/mL in each Group Race Mostly male
Slide 7: Safety: The combination of imdusiran and VTP-300 was well-tolerated
Safety: The combination of imdusiran and VTP-300 was well-tolerated Imdusiran Group A Group B Study Total Subjects, N (%) [Events] Lead-in (N=40) VTP-300 (N=20) Placebo (N=20) (N=40) Any TEAE 22 (55%) [44] 12 (60%) [22] 12 (60%) [24] 30 (75%) [90] Grade 1 19 (47.5%) [40] 7 (36.8%) [16] 5 (27.8%) [12
Slide 8: Results: Lower HBsAg levels maintained over time in VTP-300 group
Results: Lower HBsAg levels maintained over time in VTP-300 group HBsAg Thresholds Achieved by Visit Mean [SE] Log10 HBsAg Level by Visit VTP-300 Cohort A: VTP-300 (N=20) Cohort B: placebo (N=20) imdusiran doses doses N=19* N=19 N=19* NA d/c assessment Log10 HBsAg (IU/mL) Subject number * p < 0.05 N
Slide 9: Results: Individual Subject HBsAg Declines by Treatment Group
Results: Individual Subject HBsAg Declines by Treatment Group Group A (VTP-300) Individual Subject HBsAg Declines Group B (placebo) Individual Subject HBsAg Declines VTP-300 imdusiran doses doses NA d/c assessment: N=16 discontinued imdusiran doses NA d/c assessment: N=10 discontinued NA restart sub
Slide 10: Results: More subjects in Group A/VTP-300 stopped NA treatment
Results: More subjects in Group A/VTP-300 stopped NA treatment Time off of HBV DNA <LLOQ HBsAg level (IU/mL) NA therapy most recent visit at most recent visit NA Discontinuation Summary Group A Group B 14% N, (%) VTP-300 placebo 7% Group A‡ 36% 36% Stopped NA treatment after 50% 50% 50% Week 48# (N=
Slide 11: Conclusions
Conclusions Imdusiran 60 mg every 8 weeks for 24 weeks followed by VTP-300 or placebo was well-tolerated The combination of imdusiran and VTP-300 led to maintenance of lower HBsAg levels during the post-treatment follow-up period Nucleos(t)ide analogue discontinuation was achieved in the majority of
Slide 12: Additional imdusiran and VTP-300 data
Additional imdusiran and VTP-300 data: Please see Abstract #2823 (Poster WED-375): Yuen, MF et al., VTP-300 immunotherapeutic, plus low dose PD-1 inhibitor, nivolumab, continues to show meaningful, sustained reductions in HBsAg levels The IM-PROVE II (AB-729-202) low dose nivolumab arm (Group C) is
Slide 13: Acknowledgements
Acknowledgements Arbutus Biopharma and Barinthus Biotherapeutics thank all participating subjects and their families, the Investigators and site staff, Novotech CRO, Eurofins, Maksym Chernyakhovskyy (Arbutus) and Crystal Grant (Arbutus) for data management assistance, Deepa Patel (Arbutus) and Derec