# A New HBV Drug For Establishing Durable Antiviral Efficacy of HBV Treatment

> **NIH NIH R43** · HBVTECH · 2021 · $300,000

## Abstract

It is estimated that 292 million people in the world are chronically infected with hepatitis B virus
(HBV). Nearly 1 million patients died from HBV related liver diseases each year. HBV
treatment with interferons and nucleos/tide analogues or new drugs face two challenges: 1.
Can’t achieve sustained antiviral efficacy and drug withdrawal frequently leads to HBV relapse
and flares up of liver injury, outcomes of which can be severe or fatal; and 2. Rarely cure HBV
infection after many years of treatment. A key step should be taken to reach the goal of HBV
functional cure set by NIH and FDA, i.e. developing new HBV drugs that aim at achieving
durable antiviral efficacy of HBV treatment and allow drug cessation without HBV relapse. HBV
drug withdrawal lifts inhibition of HBV replication, leading to producing and releasing more
virions that will infect more cells, i.e. HBV relapse, because of insufficient anti-HBs antibody that
can’t match HBV particle level, leaving virions unneutralized, facilitating new spreads of infection
or HBV relapse. Thus, the fundamental problem causing HBV relapse after drug stops is a lack
of sufficient anti-HBs antibody, which is associated with defects in HBsAg-specific B cells. To
effectively address this significant challenge of non-durable antiviral efficacy of HBV therapy,
endogenous anti-HBs production must be expanded independently of B cells. HBVtech aims to
develop AAV vector-based gene therapy to expand endogenous anti-HBs production capacity.
To develop this new therapy, HBVtech must establish two in vivo feasibilities: 1. ability to
express sustained high level of anti-HBs; and 2. the expressed anti-HBs antibodies being
capable of blocking HBV infection in HBV infected chimeric mice. HBVtech has constructed four
AAV anti-HBs vectors that carry anti-HBs genes for expressing anti-HBs antibody.
Subsequently, HBVtech evaluated the in vivo expression ability of each AAV-anti-HBs vector in
mice and has proven the first ability that three of four AAV-anti-HBs vectors can express high
level (>100?g/ml) of anti-HBs antibodies for at least 25-week in transduced mice. This proven
ability to express sustained high level of anti-HBs antibody by AAV vectors has laid the critical
foundation for the success of this drug. The objective of this Phase I study is to ascertain the 2nd
ability that the expressed anti-HBs by three AAV-anti-HBs vectors effectively blocks in vivo HBV
infection by establishing durable efficacy after entecavir stops. By completing this phase I study,
two key in vivo feasibilities will have been established. HBVtech will file new patent application
to protect AAV-anti-HBs vectors. Three AAV-anti-HBs vectors will enter phase II development. If
successful, this new HBV therapy will shorten infinite HBV treatment to a finite course and
benefit millions of patients, representing a critical progress in HBV cure.

## Key facts

- **NIH application ID:** 10150642
- **Project number:** 1R43AI155066-01A1
- **Recipient organization:** HBVTECH
- **Principal Investigator:** Yong-Yuan Zhang
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150642

## Citation

> US National Institutes of Health, RePORTER application 10150642, A New HBV Drug For Establishing Durable Antiviral Efficacy of HBV Treatment (1R43AI155066-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10150642. Licensed CC0.

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