Checkpoint Modifier Vaccine Shows Potential to Increase T-cell Response in Patients With HBV

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First-in-human data with low dose VRON-0200 were presented at the EASL 2024 congress.

Ed Gane, MBChB, MD, FRACP, MNZM, professor medicine, University of Auckland

Ed Gane, MBChB, MD, FRACP, MNZM

Credit: Linkedin

VRON-0200, a checkpoint-modifier containing vaccine, was well-tolerated and caused some increases in T-cell response in patients with chronic hepatitis B virus (HBV).

The therapy expresses a herpes simplex virus type 1 glycoprotein D fused with HBV core and polymerase antigens and is designed to enhance CD8+ T cell responses. Data from a phase 1b study (NCT06070051) of VRON-0200 were presented at the European Association for the Study of the Liver 2024 Congress, held June 508, in Milan, Italy, by Ed Gane, MBChB, MD, FRACP, MNZM, professor of medicine, University of Auckland.1

"Patients with chronic HBV infection suffer from immune exhaustion. To date, immunomodulatory therapies, including therapeutic vaccination, have failed to stimulate HBV-specific T- and B-cell responses. These immunologic data are exciting because a single intramuscular injection of VRON-0200 was able to induce T cell responses in the majority of patients, most of whom had little, to no, documented immunity prior to vaccination. Being able to stimulate T cells in this patient population, with a good safety profile and ease of administration, are all critical components for potential therapies for HBV functional cure.I look forward to seeing additional data from this ongoing study,” Gane said in a statement.2

The data are from 13 patients in the safety set and 9 evaluable for immunogenicity as of May 1, 2024, and include up to 91 days of follow-up. Participants received a single intramuscular low dose (1x1010 vp) of VRON-0200. VRON-0200 was well tolerated, with no serious adverse events (SAEs), 5 grade 1 AEs in 3 patients and no significant changes in liver function. There were no study participant discontinuations.

READ MORE: Etranacogene Dezaparvovec Demonstrates Safety and Efficacy in Patients With a History of Chronic HCV/HBV

Most of the 9 patients evaluable for immunogenicity had limited T-cell responses below the lower limit of detection. At 28 days after infusion, 5 of 9 patients responded (ELISpot above lower limit of detection at 2 consecutive timepoints) with increases in core and polymerase T-cell responses. Overall, responses increased 2.4-fold from baseline; this was more pronounced in responders with a 4-fold increase. At last follow-up, 3 patients had T-cell responses maintained above baseline. This first cohort is continuing to be evaluated, with boost vaccinations underway. A high dose cohort is enrolling and a combination cohort is planned for later in 2024.1

"Immune-based treatments are now considered necessary for functional cure of Chronic HBV. These VRON-0200 data - the first-ever for a checkpoint modifier containing T cell vaccine of any kind – showed that VRON-0200 can induce immune responses in chronically HBV-infected patients, even after a single low dose vaccination.Building upon these positive safety and immunogenicity data, we are now exploring ways to further evaluate VRON-0200, alone and in combination with other investigational agents, which we will be announcing very soon," study author Sue Currie, PhD, chief operating officer, Virion, added.2 "These data represent a critical first step in Virion's mission to bring a safe, well tolerated, easy to administer, and immunogenic interferon-sparing functional cure immunotherapy to the almost 300 million patients living with chronic HBV.We look forward to sharing more data later this year."

REFERENCES
1. Gane EJ, Currie SL, Luber A, et al. Promising first-in-human, first-in-class, Phase 1b immunogenicity data of VRON-0200, a novel checkpoint modifier containing immunotherapy, for HBV functional cure. Presented at: EASL Congress 2024; June 5-8; Milan, Italy. LBP-018
2. Virion Therapeutics Reports Positive First-in-human, First-in-class, Phase 1b Immunogenicity Data of VRON-0200, a Novel Checkpoint Modifier for HBV Functional Cure at EASL Congress. News release. Virion Therapeutics. June 5, 2024. https://www.prnewswire.com/news-releases/virion-therapeutics-reports-positive-first-in-human-first-in-class-phase-1b-immunogenicity-data-of-vron-0200-a-novel-checkpoint-modifier-for-hbv-functional-cure-at-easl-congress-302161948.html
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