New preliminary data is announced at AASL from the Phase IIa IM-PROVE II clinical trial (AB 729202) of people with chronic hepatitis B virus

The new data are from an additional cohort of participants (Group C) who received repeat doses of imdusiran, Arbutus’ RNAi therapeutic, followed by Barinthus Bio's T-cell stimulating immunotherapeutic, VTP 300, with or without low-dose nivolumab, an anti-PD-1 monoclonal antibody. The data indicated that Group C participants receiving nivolumab experienced increased rates of HBsAg loss (defined as HBsAg <LLOQ [0.05 IU/mL]) compared to Group A and B participants who received imdusiran and VTP 300 or placebo. The data from Groups A and B were previously presented at the European Association for the Study of the Liver (EASL) Congress in June 2024.

Group C enrolled a total of 22 non-cirrhotic, virally suppressed cHBV participants with HBsAg ≥100 to <5,000 IU/mL at screening who were on stable nucleos(t)ide analogue (NUC) therapy for ≥12 months. Thirteen of these participants were eligible to receive low-dose nivolumab and nine participants were not eligible, based on the trial criteria.

The preliminary data from Group C included data to Week 48 (20/22 participants) and showed the following: i) Imdusiran lead-in treatment led to a mean decline from baseline in HBsAg consistent with data from Groups A and B. ii) Significantly greater mean declines in HBsAg levels (p <0.017) were seen in Group C participants who received imdusiran and VTP 300 with nivolumab, at Week 48 compared with Groups A and B and Group C without nivolumab. iii) 23% of participants (3/13) in the group receiving imdusiran, VTP 300 and low-dose nivolumab achieved HBsAg loss by Week 48. iv) Increases in soluble immune biomarkers associated with immune checkpoint proteins, inflammation, and T-cell activation were observed in participants who had HBsAg loss at any point through Week 48. v) The Group C treatment regimen with nivolumab was generally well tolerated and did not result in any immune-related adverse events. 

"These data demonstrated the impact of the combination of an immune stimulant such as VTP 300 and a low dose of the checkpoint inhibitor nivolumab in helping participants reach HBsAg loss,” said Dr. Leon Hooftman, Chief Medical Officer of Barinthus Bio. “While these are early data, the imdusiran, VTP 300 and low-dose nivolumab regimen is promising and is consistent with the data we are seeing from our HBV003 trial of VTP 300 plus low-dose nivolumab.”

The poster from the presentation at AASLD 2024 can be accessed through the Arbutus website under Publications.

The IM-PROVE II Phase IIa clinical trial initially enrolled 40 non-cirrhotic, virally suppressed cHBV participants that were on stable NUC therapy in Groups A and B. These participants received imdusiran (60mg every 8 weeks) for 24 weeks with on-going NUC therapy and were then randomized to receive either VTP 300 (Group A) or placebo (Group B) at Weeks 26 and 30 (and conditionally at Week 38 if they experienced a >0.5 log10 decline in HBsAg between Weeks 26 and 34). 

This trial was amended to include an additional cohort (Group C) which enrolled 22 participants, 13 of which were eligible to receive imdusiran (60mg every 8 weeks) for 24 weeks with ongoing NUC therapy followed by VTP 300 at Weeks 26 and 30 plus up to two low doses of nivolumab (0.3 mg/kg), an approved PD-1 monoclonal antibody at Week 30. The remaining 9 participants received the imdusiran/NUC/VTP 300 regimen without nivolumab. Participants could receive a second dose of VTP 300 ± low-dose nivolumab at Week 38 if their HBsAg was ≥10 IU/mL at Week 34.

Upon completion of the treatment period at Week 48, all participants who met certain criteria could discontinue NUC therapy and be followed for an additional 48 weeks. Those who did not meet the criteria continued on NUC therapy for an additional 24 weeks of follow-up.