Infection Intel: Barinthus Bio Announces Promising Results From Phase 2b Hepatitis B Trial

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Barinthus Biotherapeutics shared encouraging results from its ongoing Phase 2b HBV003 trial, which evaluates VTP-300, an immunotherapy combined with low-dose nivolumab for chronic hepatitis B (CHB). Out of 121 participants, 8 achieved HBsAg loss, with 2 meeting the functional cure criteria. Notably, two participants who discontinued nucleos(t)ide analogue (NUC) therapy seroconverted to HBsAb positivity, indicating potential long-term infection control.

The trial focuses on participants with HBsAg levels ≤200 IU/mL, showing the strongest responses. Among those assessed for NUC discontinuation, 66% maintained therapy-free status, and durable HBsAg declines were observed across treatment groups. Preliminary safety data confirmed that the combination therapy was well tolerated without significant adverse events.

These findings highlight VTP-300's potential to achieve functional cures for CHB, addressing a critical challenge in managing hepatitis B. Barinthus Bio aims to further optimize dosing regimens and explore its platform's broader applications, positioning the company as a leader in innovative infectious disease therapies.

To learn more, Infection Control Today^® (ICT^®) interviewed LeonHooftman, MD, the chief medical officer for Barinthus Biotherapeutics.

ICT: Can you explain VTP-300's mechanism of action and how it differs from existing hepatitis B treatments?

Leon Hooftman, MD: Experts believe 3 key components exist for the successful treatment of hepatitis B. The first component requires inhibiting virus replication, which is effectively managed by nucleoside analogs, or NUCs, which are the current standard of care. The second component requires reducing the burden of hepatitis B surface antigen, where antisense oligonucleotides or siRNAs can be effective. However, once you stop using these treatments, the levels of surface antigens tend to rebound. This is where VTP-300 comes in as the third component as an immunotherapy. VTP-300 is used to stimulate the immune system and encourage the production of de novo, disease-specific T cells, enabling the immune system to control the virus in the long term and potentially reach a functional cure.

ICT: What were the key findings from the clinical data presented at AASLD: The Liver Meeting?

LH: We presented data from 2 ongoing Phase 2 trials at AASLD. The first was an interim update from HBV003, which is looking at dosing regimens of VTP-300 in combination with low-dose nivolumab, an anti-PD-1 monoclonal antibody, in patients with low starting levels of hepatitis B surface antigen (below 200 IU/mL). The second was updated data from the IM-PROVE II study, focusing on Group C, who received repeat doses of imdusiran, Arbutus’ RNAi therapeutic, followed by VTP-300, with or without low-dose nivolumab.

We had some very encouraging data from HBV003, seeing that eight participants had experienced hepatitis B surface antigen loss, one of the key criteria for a functional cure. 33% (2/6) participants who had discontinued and remained off their NUC therapy had actually met functional cure criteria. We also saw participants seroconverting to be positive for hepatitis B surface antibodies, which is an indication that the immune system has taken long-term control over the virus. Follow up is continuing as the trial is ongoing, but a key point across all the groups is that we are seeing durability of response, meaning that in those who are experiencing surface antigen loss, we are not seeing large rebounds for up to nine and half months in one case so far.

As I mentioned, we also presented data from the IM-PROVE II study, which looked at a broader population of participants with starting surface antigen levels between 100 and 5,000 IU/mL. The key takeaways from this data set were that Group C participants, who received imdusiran, VTP-300 and nivolumab, had a significantly greater mean surface antigen decline at Week 48 than the other groups. 23% of participants in Group C also had hepatitis B surface antigen loss at Week 48, which is unique compared to the other groups.

As you can see, this was a very exciting conference for us as a company, and we are looking to see the results when they are available.

ICT: Hepatitis B is often referred to as a 'silent epidemic.' How does VTP-300 address the challenges posed by asymptomatic infections?

LH: According to the WHO, only 13% of people with hepatitis B are aware of their infection. Currently, the biggest challenge in terms of treatment is that there is no cure for hepatitis B. This means that as a patient, even if you are diagnosed, there is no solution for you other than to start lifelong treatment on NUCs.

However, we saw in the case of hepatitis C that diagnosis rates rose following the production of a cure. People with hepatitis C had a viable option for a cure, and so were more likely to get tested for it.

As we progress with the clinical trials of VTP-300, this is something that we are bearing in mind, and we may see a very similar picture when a functional cure is reached for hepatitis B.

ICT: What are the next steps in the development and clinical trials of VTP-300 following the latest data presentation?

LH: The trials are still ongoing, and we have yet to finalize any plans. However, the data are maturing, and it’s a matter of waiting to see how the results continue to develop. By EASL next year, we expect to have a much clearer understanding of the efficacy and safety of VTP-300. At that point, we expect to finalize our development plan.

What combination will be involved will be dependent on the data.