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 more than 300 million people, including up to 2.4 million in the U.S. and 14 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 820,000 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 10.5% of all those infected were aware of their infection.[2] As a result of low diagnosis rates and strict treatment eligibility guidelines, in 2019 only an estimated 6.6 million of the people with chronic HBV were on 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, a sequential combination immunotherapy consisting of an initial dose using the ChAdOx platform, followed by a further dose(s) using MVA encoding multiple hepatitis B antigens including a 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, has been initiated to investigate the timing of administration of anti-PD-1 and additional doses of MVA-HBV. In addition, Barinthus Biotherapeutics and Arbutus are investigating siRNA (AB-729) + VTP-300 in CHB patients.

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

VTP-200: A potential non-invasive treatment for persistent high-risk HPV

Unmet need

It is estimated that approximately 291 million women worldwide are carriers of human papillomavirus (HPV) DNA.[6] Persistent genital HPV infection is responsible for almost all cases of cervical pre-cancerous lesions, which can lead to cervical carcinoma.[7] Cervical cancer was the fourth most common cancer in women in 2020, with approximately 604,000 cases and 342,000 deaths from the disease worldwide.[7] The American Cancer Society predicts that, in 2022, about 14,100 new cases of invasive cervical cancer were diagnosed in the US with over 4,280 women dying from the disease.[8] Over 95% of cervical cancers are caused by HPV infection.[7] Treatment of high-grade cervical lesions requires invasive interventions, such as Loop Electrosurgical Excision Procedure (LEEP), or cryoablation,[7] which are associated with potentially dangerous complications.[9] Thus, there is an unmet need for non-invasive therapeutic options to treat existing HPV infections and pre-cancerous lesions in order to prevent cervical cancer.

Our approach

VTP-200, a sequential combination immunotherapy consisting of an initial dose using the ChAdOx platform and further dose using MVA encoding multiple HPV antigens. VTP-200 is being developed as a potential non-invasive treatment for persistent high-risk HPV, or hrHPV, infections, and associated pre-cancerous lesions.

Development status

Extensive preclinical studies were conducted with VTP-200, with resulting data showing that VTP-200 was well tolerated in preclinical toxicology studies and highly immunogenic in inbred and outbred mice. The ongoing HPV001 Phase 1b/2 clinical trial of VTP-200 is designed to assess the safety and efficacy of VTP-200 and determine the optimal immunotherapeutic dose regimen. Barinthus Biotherapeutics plans to enroll 105 healthy women with low grade lesions who have had persistent hrHPV for at least six months.

Key references

• Hancock, G., et al. 2019. A multi-genotype therapeutic human papillomavirus vaccine elicits potent T cell responses to conserved regions of early proteins. Nature Scientific Reports, 9(1), pp.1-12.
• Hellner, K. and Dorrell, L., 2017. Recent advances in understanding and preventing human papillomavirus-related disease. F1000Research, 6.
• Adams, A., et al. 2014. Human papillomavirus induced transformation in cervical and head and neck cancers. Cancers, 6(3), pp.1793-1820.
• Hancock, G., Hellner, K. and Dorrell, L., 2018. Therapeutic HPV vaccines. Best Practice & Research Clinical Obstetrics & Gynaecology, 47, pp.59-72.
• Ewer, K.J., Lambe, T., Rollier, C.S., Spencer, A.J., Hill, A.V. and Dorrell, L., 2016. Viral vectors as vaccine platforms: from immunogenicity to impact. Current opinion in immunology, 41, pp.47-54.

Clinical trial references

HPV001 – NCT04607850 (clinicaltrials.gov)