Virion Therapeutics Reports First-Ever Clinical Responses with VRON-0200, a Novel Checkpoint Modifier for HBV Functional Cure, at AASLD's The Liver Meeting®

Highlights from the Data Presentation

• Ongoing safety (N=25) and immunogenicity (n=22), and first report of anti-HBV activity, presented in chronically HBV-infected patients following a single, prime-only intramuscular injection of VRON-0200
• Over 4,952 patient safety days, VRON-0200 was well tolerated, with no serious adverse events (SAEs), study patient discontinuations, or laboratory abnormalities observed
• VRON-0200 induced CD8+ T cell responses in one third (7 of 22) of patients
  • Responses were observed even in patients with limited pre-existing immunity
  • A 5.5-fold increase in T cell responses at Day 28 was observed in the 7 responders
• Hepatitis B surface antigen declines ranging from -0.4 to -2.3 log₁₀ IU/mL were observed, even though VRON-0200 does not directly target S-antigen, indicating anti-HBV immune activity

PHILADELPHIA, Nov. 19, 2024 /PRNewswire/ -- Virion Therapeutics, LLC, a clinical-stage biotechnology company, developing novel T cell-based immunotherapies, today announced positive immunologic and continued safety and tolerability data, and anti-HBV immune responses, from the first-ever human study of its novel, first-in-class, checkpoint modifier immunotherapy, VRON-0200, for HBV functional cure, presented by Professor Grace Wong, M.D., from the Chinese University of Hong Kong, as a late breaker poster presentation at The Liver Meeting^® 2024 (The American Association for the Study of the Liver), in San Diego, California, US.

These Phase 1b data, on the first 25 chronically infected hepatitis B patients, on nucleos(t)ide antiviral therapy, all of whom received a single, intramuscular (i.m.) injection of VRON-0200, demonstrated that it was safe and well-tolerated, with no significant adverse events reported and no clinically relevant abnormalities in laboratory assessments, including liver function tests. In 22 patients who had at least 28 days of immunologic follow up, a 5.5-fold increase in T cell responses was observed in 7 patients (32%), post-vaccination, with most maintaining responses above their baseline values out to day 91.  Additionally, four patients were observed to have HBV surface antigen (HBsAg) declines ranging from -0.4 to -2.3 log₁₀ IU/mL, after a single i.m. dose.

Professor Wong commented: "Restoring immune function in chronically HBV-infected patients is needed in order to be able to discontinue HBV treatment and eliminate the infection. These results are highly promising for this chronically infected patient population, most of whom were infected at birth, in that a single VRON-0200 injection was able to both stimulate T cell responses, and lower HBsAg, in the blood, but also, that it is safe and well tolerated. The observed declines in HBsAg are of great interest given that VRON-0200 does not directly target HBsAg, and this suggests immune control of the virus in these patients. I look forward to seeing additional data, and longer follow up, from this study."

"These data highlight the potential of VRON-0200 as a simple, easy-to-administer, IFN-sparing immunotherapy, alone or in combination, for HBV functional cure," said Dr. Sue Currie, COO of Virion, and one of the study authors. "VRON-0200 is the first new immunotherapy, other than monoclonal antibody checkpoint inhibitors and pegylated-interferon, to lower HBsAg without directly targeting it. As a result of these positive data, we are now investigating our first combination therapy with VRON-0200 with a cohort that includes elebsiran (siRNA) plus tobevibart (mAb), with the goal to potentially improve responses and bring a cure to the almost 300 million persons living with chronic HBV.  We look forward to sharing more results in early 2025."  

Professor Ed Gane, M.D., from the University of Auckland, and one of the study authors, commented: "The non-immunologic/artificial removal of HBsAg (e.g., siRNA, small molecules), has not been shown to achieve durable off-treatment responses, and may not restore the needed immunity to control HBV infection. What makes these results so exciting is that a single VRON-0200 dose was able to produce HBsAg declines, showing evidence of anti-HBV immune control in these chronically infected patients.  These data, and the upcoming data from the now enrolling combination cohort, will inform future strategies for Functional Cure therapies."

Summary of VRON-0200 Phase 1b clinical trial design

• VRON-0200 is a Phase 1b, multi-center, open-label, dose escalation, prime only, and prime plus boost, therapeutic immunotherapy study to evaluate the safety, tolerability, immunology, and other clinical measures:
  • Inclusion criteria: Non-cirrhotic, HBeAg positive or negative, chronic hepatitis B patients currently taking nucleos(t)ide antiviral therapy with HBV DNA < 40 IU/mL and HBsAg < 500 IU/mL (< 1,000 IU/mL for Cohort 3)
  • Dose escalation: Cohort 1 (low dose) (ENROLLED); Cohort 2 (high dose) (ENROLLED)
  • Prime or Prime-Boost: In each cohort, patients are randomized to receive either a prime dose only or a prime and boost regimen
  • Cohort 3: patients are randomized to receive VRON-0200 prime plus 6 monthly subcutaneous doses of elebsiran and tobevibart starting starting on Day 28, alone, or with a boost at Day 196 (ENROLLING)

More details of the study can be found at ClinicalTrials.gov (Identifier: NCT06070051).

About Chronic Hepatitis B
Despite a preventative vaccine, cases of chronic hepatitis B (HBV) continue to rise, with an estimated 296 million persons infected worldwide and 820,000 deaths per year from HBV-related liver complications. Chronic HBV remains a global health issue with a high unmet medical need since there is no cure available. The current standard of care requires lifelong antiviral therapy to maintain control of the virus.

About VRON-0200
VRON-0200 is a therapeutic immunotherapy, administered by intramuscular injection, designed with the goal of providing a functional cure for chronic HBV infection. While the virus itself stimulates HBV-specific CD8+ T cells, for those patients that can't clear the initial infection, their T cells soon become exhausted, placing limits on their ability to proliferate and control the virus. Preclinical data support the hypothesis that VRON-0200, through checkpoint modification, can amplify, broaden, and enhance T cell responses that may include T cells that are not normally activated during a chronic HBV infection, which results in improved viral control. An ongoing Phase 1b trial has shown VRON-0200 to be safe, well tolerated, and immunogenic, in chronically HBV-infected patients on nucleos(t)ide therapy. 

About Virion Therapeutics (Virion)
Virion Therapeutics, LLC is a clinical-stage company developing novel T cell-based immunotherapies to cure cancer and chronic infectious diseases that utilize proprietary genetically encoded checkpoint modifiers to enhance and broaden CD8+ T cell responses to a tumor or chronic infection. Founded in early 2018 to advance technology licensed from The Wistar Institute, an international leader in biomedical research, Virion has since developed a robust pipeline, including its lead VRON-0200 clinical program, and several additional IND-enabling programs, including its VRON-0300 oncology program for advanced solid tumors, leveraging its proprietary platform technologies.

To learn more, visit www.VirionTx.com

Contact:
Virion Therapeutics, LLC, Dr. Sue Currie, Chief Operating Officer
[email protected]

SOURCE Virion Therapeutics, LLC