Slide 1: Efficacy and safety of xalnesiran with and without an immunomodulator in chronic hepatitis B
Efficacy and safety of xalnesiran with and without an immunomodulator in chronic hepatitis B Jinlin Hou1, Qing Xie2, Wenhong Zhang3, Junqi Niu4, Hong Tang5, Xieer Liang1, Apinya Leerapun6 Cong Cheng7, Katerina Glavini8, Sudip Das9, Remi Kazma8, Ethan Chen10, Bernadette Surujbally9, Ruchi Upmanyu9 an
Slide 2: Disclosure of Conflict of Interest
Disclosure of Conflict of Interest ◆ Advisory committee for GSK, Gilead Sciences. Consultant for Aligos. Grant/research support from Roche 2
Slide 3: Novel Therapeutic Approach to Achieve Functional Cure
Novel Therapeutic Approach to Achieve Functional Cure* Combination of Direct Acting Antiviral plus Immunomodulator Direct Acting Antiviral ▪ Liver-targeted oligonucleotide Xalnesiran (HBV siRNA) ▪ Targeting the HBV genome S open reading frame Immunomodulators ▪ Double pro-drug selectively activated
Slide 4: Piranga Study: Treatment Arms
Piranga Study: Treatment Arms Primary endpoint is percentage of participants with HBsAg loss** at 24 weeks post-EOT Participants Treatment* Follow up* ▪ CHB infection ≥6 End of Primary End of Treatment (EOT) Endpoint** Study months Baseline Wk 12 Wk 24 Wk 36 Wk 48 FU Wk 24 FU Wk 48 ▪ On NUC (ETV or
Slide 5: Piranga Study: Baseline Characteristics
Piranga Study: Baseline Characteristics Well balanced between the treatment arms Xalnesiran 100mg Xalnesiran 200mg Xalnesiran 200mg Xalnesiran 200mg + NUC + NUC + ruzotolimod + Peg-IFN-α NUC control + NUC + NUC (N=30) (N=30) (N=34) (N=30) (N=36) Age yrs, mean (sd) 43 (10.7) 40 (11.0) 43 (8.5) 38 (9.
Slide 6: Piranga Results: HBsAg loss at EOT and Primary Endpoint
Piranga Results: HBsAg loss at EOT and Primary Endpoint Highest HBsAg loss rates with xalnesiran and immunomodulator (Peg-IFN-α or ruzotolimod) ▪ HBsAg loss observed only in participants with baseline HBsAg<1000 IU/mL ▪ HBsAg seroconversion at 24 weeks post-EOT: ▪ n=6 xalnesiran+Peg-IFN-α ▪ n=1 xaln
Slide 7: Piranga Results: HBsAg loss for participants with baseline HBsAg <1000 IU/mL
Piranga Results: HBsAg loss at EOT and Primary Endpoint for participants with baseline HBsAg <1000 IU/mL Highest HBsAg loss rates with xalnesiran and immunomodulator (Peg-IFN-α or ruzotolimod) ▪ HBsAg seroconversion at 24 weeks post-EOT: ▪ n=6 xalnesiran+Peg-IFN-α ▪ n=1 xalnesiran+ruzotolimod ▪ n=1
Slide 8: Piranga Study Results: HBsAg Reductions
Piranga Study Results: HBsAg Reductions Mean (sd) declines from baseline in HBsAg of 1.2–1.7 log10 IU/mL at 24 weeks post-EOT Treatment Follow up -0.20 -0.19 -1.19 -1.58 -1.47 -1.71 -1.71 -1.93 -2.18 -2.22 8
Slide 9: Piranga Study Results: Summary of Adverse Events
Piranga Study Results: Summary of Adverse Events All treatments were generally safe and well tolerated Xalnesiran 200mg Xalnesiran 200mg Xalnesiran 100mg Xalnesiran 200mg NUC control + ruzotolimod + Peg-IFN-α + NUC + NUC + NUC + NUC (N=30) (N=30) (N=34) (N=30) (N=36) Total number of participants wit
Slide 10: Piranga Study: Key Takeaways
Piranga Study: Key Takeaways ● Combination of xalnesiran with ruzotolimod or Peg-IFN-α led to higher HBsAg loss rates at 24 weeks post-EOT ● HBsAg loss observed only in participants with baseline HBsAg <1000 IU/mL ● All treatments were generally safe and well tolerated ● Ongoing arms of this platfor
Slide 11: Acknowledgments
Acknowledgments Study participants and their families Clinical study partners ▪ Auckland Clinical Studies Limited, New Zealand – Edward Gane ▪ Middlemore Clinical Trials, New Zealand – Tien Huey Lim ▪ Nanfang Hospital, Southern Medical University, China – Jinlin Hou ▪ Chuncheon Sacred Heart Hospital