Slide 1: Evidence of T Cell Restoration after siRNA Therapy
Evidence of T Cell Restoration after siRNA Therapy Emily Thi HBV Cure Workshop 2022 Toronto, Canada November 2, 2022 NASDAQ: ABUS www.arbutusbio.com
Slide 2: Disclosure Statement
Disclosure Statement The authors affiliated with Arbutus Biopharma are current and former employees and may hold company stock.
Slide 3: Rationale: HBsAg and Treatment Response
Rationale: HBsAg and Treatment Response Low baseline and rapid change in HBsAg levels has been associated with better responses in patients treated with: • pegIFN-α • Nucleo(s)tide analogues (NA) • Checkpoint inhibitors • Therapeutic vaccines Sonneveld et al., Hepatol., 2013 Low HBsAg and/or undetec
Slide 4: AB-729, an RNAi Therapeutic for CHB
AB-729, an RNAi Therapeutic for CHB AB-729 is a subcutaneously administered single trigger GalNAc-conjugated siRNA therapeutic candidate Targets all HBV RNA leading to reduction of HBV antigens including HBsAg AB-729 is currently in Phase 2 development for the treatment of CHB in combination with ot
Slide 5: AB-729-001 Study Design and Baseline Characteristics
AB-729-001 HBV DNA- Baseline Measure# Cohort E‡ Cohort F (N=7) (N=7) 3-part study examining safety and Age in years, mean 45.1 44.0 pharmacodynamics of single and repeat doses (range) (33 – 63) (31 – 59) of AB-729 in healthy subjects and CHB subjects Male gender, n (%) 4 (57) 4 (57) BMI, mean (SD) 2
Slide 6: HBV-Specific T Cell Activation Markers are Upregulated in CHB Subjects Undergoing AB-729 Dosing
HBV-Specific T Cell Activation Markers are Upregulated in CHB Subjects Undergoing AB-729 Dosing Upregulation of HBV-specific T cell activation markers observed in all 7 subjects assessed to date for whom PBMC samples were available 6
Slide 7: HBV-Specific T Cell Activation Markers are Upregulated in CHB Subjects Undergoing AB-729 Dosing
HBV-Specific T Cell Activation Markers are Upregulated in CHB Subjects Undergoing AB-729 Dosing Upregulation of HBV-specific T cell activation markers observed in all 7 subjects assessed to date for whom PBMC samples were available Mild to moderate ALT elevations observed in some NA-suppressed CHB s
Slide 8: HBV-Specific T Cell Activation Markers are Upregulated in CHB Subjects Undergoing AB-729 Dosing
HBV-Specific T Cell Activation Markers are Upregulated in CHB Subjects Undergoing AB-729 Dosing 60 mg Q4W Subject 40 60 mg Q4W Subject 41 60 mg Q4W Subject 43 HBV-IFNγ spots/1E6 cells 5 5 5 SI (T cell proliferation) Elevation 150 60 HBsAg (Log10 IU/mL) 60 4 30 4 50 4 during AB-729 15 ALT (U/L) 3 20
Slide 9: HBV-Specific T Cell Activation Markers: IFN-γ Fold Increase over Baseline
HBV-Specific T Cell Activation Markers are Upregulated in CHB Subjects Undergoing AB-729 Dosing On Treatment HBsAg Nadir Follow-Up 80 60 Subject 40 IFN-γ Fold Increase 40 Subject 41 over Baseline 20 Subject 42 Q4W 15 Subject 43 Subject 44 10 Subject 48 5 Q8W Subject 53 0 0 4 8 12 16 20 24 28 32 36 4
Slide 10: Decline of CD8+ Exhausted T Cells in CHB Subjects Undergoing AB-729 Dosing
Decline of CD8+ Exhausted T Cells in CHB Subjects Undergoing AB-729 Dosing Subject 40 Subject 41 Subject 42 30 30 30 Frequency (%) In 4 out of 6 subjects, Frequency (%) Frequency (%) 20 20 20 frequency of exhausted CD8+ T cells declined at EOT and 10 10 10 persisted up to 12-16 wks after last dose o
Slide 11: Association with Clinical Outcomes
Association with Clinical Outcomes 60 mg Q4W Subject 40 HBV-IFNγ spots/1E6 cells 5 SI (T cell proliferation) HBsAg (Log10 IU/mL) 60 4 30 Subject 41 seroconverted and ALT (U/L) 3 20 HBsAg became <LLOQ at Wk 2 15 84, 40 wks after last dose of 1 10 5 AB-729 (beyond current T cell 0 0 data set) 0 4 8 12
Slide 12: Association with Clinical Outcomes
Association with Clinical Outcomes Subject 53 met pre-defined NA discontinuation criteria 60 mg Q8W Subject 48 HBV-IFNγ spots/1E6 cells 4 60 SI (T cell proliferation) and elected to stop NA HBsAg (Log10 IU/mL) 50 3 treatment 40 ALT (U/L) 2 30 Other subject did not meet 1 20 10 NA discontinuation cri
Slide 13: Summary
Summary AB-729-mediated HBsAg reduction is associated with increased HBV-specific T cell activation and proliferation from baseline in CHB subjects A decline in exhausted CD8+ T cells at end of treatment and at 12-16 weeks of follow-up suggests that HBV-specific T cell immune reawakening may be dura
Slide 14: Acknowledgments
Acknowledgments Immunology & Clinical Development Executive Management Biology Karen Sims Gastón Picchio Sharie Ganchua Timothy Eley Michael Sofia Christina Iott Elina Medvedeva Bhavna Paratala Deana Antoniello Angela Lam Kevin Gray Varun Sharma We thank the AB-729-001 patients and study investigato
Slide 15: Thank You
Thank You 15