Barinthus Biotherapeutics, which was formerly Vaccitech, is working on a functional cure for hepatitis B (HBV), and announced new data at this year’s The Liver Meeting in 2 trials looking at its immunotherapeutic candidate, VTP-300.
VTP-300 consists of an initial dose using the ChAdOx vector and a secondary dose(s) using the MVA-vectored platform, both encoding multiple hepatitis B antigens, including full-length surface, modified polymerase, and core antigens. VTP-300 is the first antigen-specific immunotherapy that has been shown to induce sustained reductions in HBsAg.
Barinthus Bio is studying VTP-300 in combination with other agents, including siRNA and low-dose anti-PD-1 antibodies, to control the infection and counterbalance the immune suppression and T cell exhaustion in the liver caused by chronic HBV infection.
HBV003 Study
This study examined a treatment dosing regimen with patients receiving VTP-300 and low-dose nivolumab. All groups received ChAdOx vector at day 1, groups 1 & 2 receive MVA with nivolumab at day 29 with group 2 being dosed again at Day 85, group 3 receives only MVA at Day 29, followed by nivolumab at Day 36 and a second MVA dose at Day 85 to evaluate PD-1 inhibition timing.
What You Should Know
Barinthus Biotherapeutics, formerly known as Vaccitech, presented encouraging interim data from its hepatitis B (HBV) clinical trials at The Liver Meeting, with their immunotherapeutic candidate, VTP-300.
The company is employing a combination therapy approach to enhance the efficacy of VTP-300. The study, known as the HBV003 trial, investigated a dosing regimen involving VTP-300 and low-dose nivolumab, along with other agents like siRNA and low-dose anti-PD-1 antibodies.
The HBV003 trial protocol is being amended to include only participants with screening HBsAg ≤200 IU/mL, as these individuals have shown the most benefit in the preliminary data.
Seventy-four out of a planned 120 virally suppressed patients with chronic hepatitis B on stable NUC therapy have been enrolled in the trial and 57 have reached day 113. VTP-300 in combination with nivolumab led to HBsAg declines in all treatment groups, particularly in participants with screening HBsAg levels ≤200 IU/mL.
The company reported the following results:
- >0.5 and >1 log drops have been observed in all groups at Day 113 in 23% and 9% of participants, respectively.
- Participants with an HBsAg level of ≤200 IU/mL at screening were more likely to have >1 log HBsAg reductions (31%) compared to those with HBsAg levels >200 IU/mL at Day 1 (2%).
- Greater mean HBsAg log reductions were observed in Group 2 (ChAdOx-HBV Day 1; MVA-HBV and nivolumab Day 29 and Day 85) but insufficient data for definitive conclusion.
- Seven participants have met the criteria for NUC discontinuation; three have discontinued and two have restarted NUC therapy.
- Preliminary safety data suggest VTP-300 in combination with nivolumab has been generally well tolerated, with no treatment-related SAEs observed or reported. Thyroid dysfunction reported in seven participants attributed to nivolumab administration which has returned to normal in four patients.
“We believe these early data are very encouraging. In HBV003, VTP-300 in combination with nivolumab continues to show meaningful and sustained HBsAg declines across all treatment groups, with the most prominent declines occurring in patients with lower baseline HBsAg levels at screening,” Barinthus Bio CEO Bill Enright, said in a statement.
The HBV003 trial protocol is currently being amended to include only participants with screening HBsAg ≤200 IU/mL. Participants with screening HBsAg ≤200 IU/mL have been observed to benefit the most in the preliminary data, with the trial protocol amendment being focused on improving the overall risk/benefit ratio.
People with thyroid autoantibodies, family history of autoimmune thyroiditis, or abnormal thyroid levels will be excluded from trial eligibility to minimize the risk of thyroiditis.
Contagion spoke to Barinthus Bio Chief Scientific Officer Nadege Pelletier, PhD, about VTP-300 earlier this year.
Reference
Barinthus Bio Presents Interim Data from Phase 2b HBV003 Trial and Phase 2a AB-729-202 Trial in Collaboration with Arbutus Biopharma in Chronic HBV Patients at AASLD. Barinthus Bio. November 9, 2023.
https://investors.barinthusbio.com/news-releases/news-release-details/barinthus-bio-presents-interim-data-phase-2b-hbv003-trial-and
