Virion Therapeutics Announces First Clinical Responses with VRON-0200 for HBV Cure at AASLD

Virion Therapeutics, LLC, a biotechnology company focused on developing novel T cell-based immunotherapies, has announced promising results from a human study of its new checkpoint modifier immunotherapy, VRON-0200. Designed for a functional cure of chronic hepatitis B virus (HBV) infection, the findings were recently presented by Professor Grace Wong, M.D., from the Chinese University of Hong Kong at The Liver Meeting® 2024 organized by the American Association for the Study of the Liver in San Diego, California.

The Phase 1b study involved 25 chronically infected HBV patients who were already on nucleos(t)ide antiviral therapy. Each participant received a single, intramuscular injection of VRON-0200. The results indicated that VRON-0200 was both safe and well-tolerated. There were no significant adverse events or clinically relevant abnormalities in laboratory tests, including liver function assessments.

Out of 22 patients who had at least 28 days of immunologic follow-up, a significant increase in T cell responses was noted in 7 patients (approximately 32%) post-vaccination. Most of these patients maintained their responses above baseline values out to day 91. Additionally, four patients showed declines in HBV surface antigen (HBsAg) ranging from -0.4 to -2.3 log10 IU/mL after just one dose of VRON-0200.

Professor Wong remarked on the necessity of restoring immune function in chronically HBV-infected patients for discontinuing antiviral therapy and eliminating the infection. She highlighted the significance of these findings, noting that VRON-0200 not only stimulated T cell responses and lowered HBsAg levels but also proved to be safe and well-tolerated. The declines in HBsAg are particularly noteworthy because VRON-0200 does not directly target this antigen, suggesting immune control of the virus.

Dr. Sue Currie, COO of Virion and one of the study authors, emphasized the potential of VRON-0200 as a straightforward, easy-to-administer immunotherapy for HBV functional cure. She pointed out that VRON-0200 is unique in reducing HBsAg levels without directly targeting it, unlike monoclonal antibody checkpoint inhibitors and pegylated-interferon. Based on these encouraging results, Virion is now exploring a combination therapy involving VRON-0200 along with elebsiran (siRNA) and tobevibart (mAb) to potentially enhance responses and advance a cure for the nearly 300 million people living with chronic HBV. Further results are anticipated in early 2025.

Professor Ed Gane, M.D., from the University of Auckland and another study author, noted that traditional methods of HBsAg removal, such as siRNA and small molecules, have not achieved durable off-treatment responses nor restored the necessary immunity to control HBV infection. What sets this study apart is that a single dose of VRON-0200 produced HBsAg declines, indicating anti-HBV immune control in chronically infected patients. The data from the ongoing combination cohort will shape future strategies for functional cure therapies.

The VRON-0200 Phase 1b clinical trial design is a multi-center, open-label, dose escalation study. It aims to evaluate the safety, tolerability, immunology, and other clinical measures of VRON-0200. The trial includes non-cirrhotic, HBeAg positive or negative chronic hepatitis B patients currently taking nucleos(t)ide antiviral therapy with HBV DNA levels below 40 IU/mL and HBsAg levels below 500 IU/mL. Different cohorts receive varying doses, and patients are randomized to receive either a prime dose only or a prime and boost regimen.

Chronic hepatitis B remains a significant global health issue, with an estimated 296 million people infected worldwide and 820,000 deaths annually due to HBV-related liver complications. Despite the availability of a preventative vaccine, the number of chronic HBV cases continues to rise, necessitating lifelong antiviral therapy to control the virus.

VRON-0200 is a therapeutic immunotherapy administered via intramuscular injection, designed to provide a functional cure for chronic HBV infection. It aims to stimulate HBV-specific CD8+ T cells and enhance immune responses that are typically compromised in chronic HBV patients. The ongoing Phase 1b trial has demonstrated VRON-0200 to be safe, well-tolerated, and effective in inducing immune responses in chronically infected patients on nucleos(t)ide therapy.