Barinthus Bio Reports Phase 2b Hepatitis B Trial Results, Including Functional Cure and HBsAb Seroconversion

Barinthus Biotherapeutics plc (NASDAQ: BRNS) has reported significant findings from its ongoing Phase 2b HBV003 clinical trial. These findings will be presented by Dr. Chun-Jen Liu on November 18, 2024, during the American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting® 2024. Barinthus Bio focuses on developing novel immunotherapeutic candidates aimed at guiding T cells to control diseases.

The HBV003 study, registered under NCT05343481, has successfully recruited 121 participants, including 69 individuals with HBsAg levels below 200 IU/mL. The trial is exploring various dosing regimens of VTP-300 combined with low-dose nivolumab, an anti-PD-1 monoclonal antibody. The latest data reveal that as of the data cut-off, eight participants achieved complete HBsAg loss, marked by HBsAg levels falling below the quantitation limit. Notably, two of these participants developed anti-hepatitis B antibodies (HBsAb), a sign of progress towards functional cure.

Dr. Chun-Jen Liu, an investigator in the HBV003 study and Director of the Hepatitis Research Center and Clinical Trial Center at National Taiwan University Hospital, highlighted the importance of these findings. He noted that achieving sustained HBsAg loss is crucial for moving chronic hepatitis B patients towards functional cures. The data indicate that VTP-300, particularly when combined with low-dose nivolumab, can lead to durable HBsAg loss. This suggests the potential for some chronic hepatitis B patients to discontinue antiviral treatment without the disease progressing.

Among the 40 participants with HBsAg below 200 IU/mL at screening who reached Day 169, 24 were eligible to discontinue nucleos(t)ide analogue (NUC) therapy. Out of these, nine participants opted to stop NUCs, and 66% (six out of nine) remained off NUC therapy, with five staying off treatment for over six months. Importantly, two of these six participants met the criteria for functional cure, and two seroconverted to HBsAb positivity.

The follow-up with the remaining participants continues to determine if they will achieve functional cure criteria. All treatment groups witnessed durable declines in HBsAg, consistent with earlier results presented at the European Association for the Study of the Liver (EASL) Congress in June 2024.

Preliminary safety data indicate that the combination of VTP-300 and low-dose nivolumab is generally well-tolerated. No treatment-related serious adverse events (SAEs) have been observed or reported as of the data cut-off.

Dr. Nadege Pelletier, Chief Scientific Officer of Barinthus Bio, expressed optimism about these Phase 2 findings. According to Dr. Pelletier, the data highlights VTP-300's capability to stimulate the immune response and induce sustained reductions in HBsAg, meeting functional cure criteria. The positive result that one participant meeting the functional cure criteria had developed antibodies against hepatitis B is promising, as HBsAb positivity is linked to long-term control of the infection by the immune system.

The HBV003 trial aims to gather crucial information on treatment dosing regimens involving VTP-300 and low-dose nivolumab. Participants in the study received various combinations of ChAdOx and MVA doses, with or without nivolumab, to evaluate the effect of anti-PD-1 inhibition timing.

VTP-300 comprises an initial dose using the ChAdOx vector followed by one or more doses using the MVA vector, encoding multiple HBsAg, including full-length surface, modified polymerase, and core antigens. It is the first antigen-specific immunotherapy shown to induce sustained reductions in HBsAg. Barinthus Bio is also investigating VTP-300 in combination with other agents like siRNA and low-dose anti-PD-1 antibodies in the ongoing IM-PROVE II trial to counteract immune suppression and T cell exhaustion in the liver caused by chronic HBV infection.

Barinthus Bio remains committed to developing innovative immunotherapeutic candidates to help individuals with serious diseases. The company leverages its proprietary platform technologies to advance treatments for infectious diseases and autoimmunity, aiming to improve patients' lives.