Infectious Diseases

VTP-300: An immunotherapeutic targeting chronic HBV infection

Unmet need

Hepatitis B is considered a “silent epidemic” because most people are asymptomatic while chronically infected.[1] Thus, they can unknowingly spread the virus to others and continue the spread of hepatitis B. Although asymptomatic, their liver can still be silently damaged.
Globally it is estimated that there are approximately 254 million people, including up to 2.4 million in the U.S. and 10.6 million in Europe, living with chronic HBV infection.[1,2] Prevalence is highest in East Asia and Africa.[3] Fewer than 10% of patients with chronic HBV infection will achieve a functional cure by using existing therapies.[4] Approximately 1.1 million people die each year from hepatitis B and related complications, such as liver cirrhosis and hepatocellular carcinoma (HCC).[2] Hepatitis B diagnosis rates remain low, and as of 2019, only an estimated 13% of all those infected were aware of their infection.[2] As a result of low diagnosis rates and strict treatment eligibility guidelines, in 2022 less than 3% of the people with chronic HBV had received antiviral treatment.[2] In recent years, screening has become more prevalent, particularly in East Asia where in some countries screening is a requirement for certain employment roles, which we believe will increase the addressable patient population.[5]

Our approach

Barinthus Biotherapeutics is developing VTP-300, an immunotherapeutic candidate consisting of an initial dose using the ChAdOx vector and a secondary dose(s) using the MVA vector, both encoding multiple HBsAg, including full-length surface, modified polymerase, and core antigens. VTP-300 is the first antigen-specific immunotherapy that has shown to induce sustained reductions in Hepatitis B surface antigen. It is likely that getting more patients to functional cure requires combination of agents with complementary mode of actions. Barinthus Biotherapeutics 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.

Development status

Barinthus Biotherapeutics has completed HBV001, its Phase 1 clinical trial of VTP-300 in healthy volunteers and chronic HBV patients and HBV002, a Phase 1/2a clinical trial in chronic HBV patients. In the HBV002 trial, VTP-300 was administered as a sequential combination in patients on stable antiviral therapy, both alone and in combination with an anti-PD-1 antibody. A Phase 2b clinical trial, HBV003, is fully enrolled and is investigating the timing of administration of anti-PD-1 and additional doses of MVA-HBV in participants with chronic hepatitis B. In addition, Barinthus Biotherapeutics and Arbutus Biopharma are investigating siRNA (AB-729) + VTP-300, with or without an anti-PD-1 in participants with chronic hepatitis B in the Phase 2a IM-PROVE II clinical clinical trial.

Key references

• Barnes, E., 2015. Therapeutic vaccines in HBV: lessons from HCV. Medical microbiology and immunology, 204(1), pp.79-86.
• Kelly, C., et al. 2016. Chronic hepatitis C viral infection subverts vaccine‐induced T‐cell immunity in humans. Hepatology, 63(5), pp.1455-1470.
• Bolte, F.J. and Rehermann, B., 2017. Tissue-resident T cells in hepatitis B: A new target for cure?
• Chinnakannan, S., et al. 2020. The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV. Vaccines, 8(2), p.184.

Clinical trial references

HBV001 – NCT04297917 (ClinicalTrials.gov)

HBV002 – NCT04778904 (ClinicalTrials.gov)

HBV003 – NCT05343481 (ClinicalTrials.gov)

AB-729-202 – ACTRN12622000317796