Barinthus Biotherapeutics (formerly Vaccitech) is working toward a functional cure for hepatitis B (HBV) and announced new data from two trials of its immunotherapy candidate VTP-300 at this year’s Liver Meeting.
VTP-300 consists of an initial dose using the ChAdOx vector and a secondary dose using the MVA vector 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 infection and balance immunosuppression and hepatic T-cell exhaustion caused by chronic HBV infection.
HBV003 research
This study examined treatment dosing regimens for patients receiving VTP-300 and low-dose nivolumab. All groups received ChAdOx vehicle on day 1, groups 1 and 2 received MVA plus nivolumab on day 29, group 2 was re-dose on day 85, and group 3 received only MVA, followed by nivolumab on day 36 and a second MVA dose on day 85 to assess duration of PD-1 inhibition.
what you should know
Barinthus Biotherapeutics (formerly known as Vaccitech) presented encouraging interim data from its hepatitis B (HBV) clinical trial and its immunotherapy candidate VTP-300 at the Liver Conference.
The company is using combination treatments 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 drugs such as siRNA and a low-dose anti-PD-1 antibody.
The HBV003 trial protocol is being revised to include only screening participants with HBsAg ≤200 IU/mL, as these individuals showed the greatest benefit in preliminary data.
Of the 120 patients with chronic hepatitis B who are virally suppressed and receiving stable NUC therapy, 74 have been enrolled in the trial and 57 have reached day 113. The combination of VTP-300 and nivolumab resulted in a decrease in HBsAg in all treatment groups, particularly in participants with screening HBsAg levels ≤200 IU/mL.
The company reported the following results:
- On Day 113, >0.5 and >1 log decline were observed in 23% and 9% of participants in all groups, respectively.
- Participants with HBsAg levels ≤200 IU/mL at screening were more likely to have >1 log HBsAg reduction (31%) compared with participants with day 1 HBsAg levels >200 IU/mL (2%).
- A greater mean log reduction in HBsAg was observed in group 2 (ChAdOx-HBV day 1; MVA-HBV and nivolumab days 29 and 85), but the data were insufficient to draw definite conclusions.
- Seven participants met criteria for NUC discontinuation; 3 patients had discontinued NUC therapy and 2 patients had restarted NUC therapy.
- Preliminary safety data indicate that VTP-300 in combination with nivolumab was generally well tolerated, with no treatment-related SAEs observed or reported. Seven participants reported thyroid dysfunction due to nivolumab administration, four of which normalized.
“We believe these early data are very encouraging. In HBV003, VTP-300 in combination with nivolumab continued to show meaningful and sustained HBsAg reductions across all treatment arms, with the most significant reductions occurring in among patients with low baseline HBsAg levels at screening,” Barinthus Bio CEO Bill Enright said in a statement.
The HBV003 trial protocol is currently being revised to include only screening participants with HBsAg ≤200 IU/mL. Preliminary data show that screening participants with HBsAg ≤200 IU/mL benefit the most, and trial protocol revisions are focused on improving the overall risk/benefit ratio.
People with thyroid autoantibodies, a family history of autoimmune thyroiditis, or abnormal thyroid levels will be excluded from trial eligibility to minimize the risk of thyroiditis.
infect Earlier this year, Dr. Nadege Pelletier, Chief Scientific Officer of Barinthus Bio, spoke with VTP-300.
refer to
Barinthus Bio presented interim data at the AASLD from its Phase 2b HBV003 trial and Phase 2a AB-729-202 trial in collaboration with Arbutus Biopharma to treat patients with chronic hepatitis B. Balintus Bio. November 9, 2023.
https://investors.barinthusbio.com/news-releases/news-release-details/barinthus-bio-presents-interim-data-phase-2b-hbv003-Trial-and