Seven biotechs to watch in the hepatitis B space

Hepatitis B is a serious liver infection that is caused by the hepatitis B virus (HBV). Around 254 million people live with hepatitis B, and 6000 people are newly infected with viral hepatitis each day, according to the World Health Organization (WHO). However, many people remain undiagnosed in several countries, and the number of people who receive treatments remains low.

Transmitted via bodily fluids, symptoms of hepatitis B include stomach aches, dark urine, fever, joint pain, vomiting, jaundice – yellowing of the whites of the eyes and the skin – and fatigue, and range from mild to severe. Acute infections often resolve on their own, however, chronic hepatitis B, which develops when the body can’t clear the virus, is yet to be cured, and current treatments only help manage symptoms.

But biotechs are striving to change that. From epigenetics and gene editing technologies to immunotherapies and combination regimens, different kinds of therapies are being trialed at the moment. In this article, we take a look at seven biotech companies with clinical drug candidates on a quest to win regulatory approval to treat hepatitis B.

Assembly Biosciences

• Therapeutic candidate: ABI-4334
• Technology: capsid assembly modulator
• Recent funding: $30.1 million grant

Chronic HBV infection is the leading cause of chronic liver disease and the need for liver transplantation, with up to 1.1 million deaths due to HBV-related causes per year. California-based Assembly Biosciences wants to change these worrying statistics with its drug candidate ABI-4334.

Its oral drug is a capsid assembly modulator, which is meant to interfere with the layer protecting the HBV virus’s genetic material, known as the capsid. Preclinically, the candidate was found to disrupt these capsids. This can prevent the virus from forming covalently closed circular DNA (cccDNA) required for replication. 

The results of a phase 2b trial were released where patients who were given 150 mg of the drug showed strong antiviral activity with a mean reduction of 2.9 log IU/mL in plasma HBV DNA – indicating a moderate viral load – over 28 days of treatment. It was also well-tolerated.

A second cohort of patients will also be tested, where they will be given a 400 mg dosage, and enrollment is ongoing. The biotech is collaborating with pharma giant Gilead Sciences, which will have the right to opt in to further development and commercialization of the drug following the phase 1b study.

Late last year, the company was awarded $30.1 million from Gilead to continue the clinical development of its drug candidates to treat hepatitis B as well as herpesviruses and hepatitis D virus (HDV).

Barinthus Biotherapeutics

• Therapeutic candidate: VTP-300
• Technology: antigen-specific immunotherapy
• Recent funding: $110.5 million public offering

Once known as Vaccitech, the U.K.- and U.S.-based biotech has now reinvented itself as Barinthus Biotherapeutics. The company’s pipeline consists of immunotherapy candidates to address a range of diseases from cancer to celiac disease and chronic hepatitis B.

Its HBV candidate VTP-300 is designed to stimulate the immune system to produce specific T cells that can control the virus. Its administration is based on a two-dose approach where each approach uses a different viral vector: a chimpanzee adenovirus (ChAdOx) prime followed by a modified vaccinia Ankara virus (MVA) boost – both of which deliver hepatitis B surface antigen (HBsAg) genes.

In a clinical study of VTP-300, 67% of participants achieved hepatitis B surface antigen (HBsAg) levels below 10 IU/mL, and 19% of participants had undetectable HBsAg. Around 76% of participants were allowed to quit the nucleotide analogue (NUC) therapy, the standard of care for HBV.

In another trial conducted in partnership with American biotech Arbutus Biopharma, 84% of participants who were on VTP-300 discontinued standard of care NUC therapy compared to 53% of patients who received a placebo.

The company last raised funds for its pipeline when it went public for $110.5 million in May 2021. 

Bluejay Therapeutics

• Therapeutic candidate: BJT-778
• Technology: monoclonal antibody
• Recent funding: $182 million series C

Another California-based biotech, Bluejay Therapeutics, specializes in liver disease therapeutics. It has a lineup of HBV drug candidates to treat the infection, which raises the risk of liver failure, liver cancer, and serious scarring of the liver called cirrhosis.

Its lead program is BJT-778 (brelovitug), a monoclonal antibody that targets HBsAg. By reducing serum HBsAg, it aims to alleviate immune cell exhaustion and allow the immune system to control the infection. The first person was dosed in a clinical trial in March. As part of its program to discover combination therapy approaches to achieve a cure for chronic hepatitis B, BJT-778 significantly increased the uptake of HBsAg compared to a control antibody in preclinical studies. BJT-778 is also being tested in a chronic hepatitis D study.

Its other HBV candidate is cavrotolimod, a spherical toll-like receptor 9 (TLR9) agonist designed to trigger innate and adaptive immune responses by binding to and activating the protein TLR9. The candidate is currently in phase 1a/1b trials. Bluejay also has BJT-628, a liver-targeted HBV transcript inhibitor, and an immunomodulator candidate in the investigational new drug and preclinical stages, respectively.

The American startup secured $182 million in a series C funding round to boost its infectious and liver diseases pipeline in May last year. 

Brii Biosciences

• Therapeutic candidate: BRII-179
• Technology: recombinant protein-based immunotherapy
• Recent funding: $155 million series C

Founded seven years ago to take aim at infectious diseases, Brii Biosciences currently has three HBV drug candidates in its arsenal. The Chinese startup’s lead HBV candidate is BRII-179, a recombinant protein-based HBV immunotherapy that expresses three HBV surface antigens – pre-S1, pre-S2, and S – and is designed to induce enhanced and broad B-cell and T-cell immunity. 

It was granted Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) at the Chinese drug regulator National Medical Products Administration (NMPA) in November 2023. Phase 2 trials of the drug are ongoing. 

Also in the phase 2 stage, elebsiran is an investigational siRNA – double-stranded RNA molecules that play a crucial role in gene silencing – that is designed to elicit antiviral activity against HBV. It was in cahoots with American company Vir Biotechnology, which handed over the exclusive rights to develop and commercialize the candidate in Greater China. The CDE granted the drug Breakthrough Therapy Designation in May last year. Results of an ongoing phase 2 study were presented at the Annual Meeting of the Asian Pacific Association for the Study of the Liver (APASL 2025) in Beijing last month. 
 

The design of one of these studies was based on insight from previous studies that a significant proportion of the chronic HBV patients are unable to develop immune responses after receiving BRII-179. The study found that 55.6% of those patients who responded to BRII-179 had lower amounts of HBsAg in the blood compared to 10% of those who did not respond to BRII-179.

Meanwhile, the company’s other hepatitis b drug candidate is tobevibart, which is a monoclonal antibody designed to block the entry of HBV into liver cells. It is also in phase 2 trials at present. 

The company has accumulated funds worth $450 million over the years, after it bagged $155 million in a series C round four years ago. It bought the licensing rights for elebsiran and tobevibart from American company Vir Biotechnology to develop and commercialize them in China.

Precision Biosciences

• Therapeutic candidate: PBGENE-HBV
• Technology: gene editing
• Recent funding: $40 million public offering

North Carolina-based company Precision Biosciences is developing its ARCUS genome editing to treat HBV, the first and only clinical-stage gene editing therapy for chronic hepatitis B.

Its candidate PBGENE-HBV, which has come out of ARCUS, is carried by lipid nanoparticles (LNPs) to liver cells called hepatocytes, inside which mRNA is translated into proteins. These proteins are then imported into the nucleus of cells, where they bind to the cccDNA and the integrated HBV DNA. It cut both strands of DNA to inactivate them, thereby decreasing HBV particles, including HBsAg.

Last week, PBGENE-HBV was bestowed the Fast Track Designation by the U.S. Food and Drug Administration (FDA). In preclinical studies, the candidate exhibited safety. A phase 1 study is currently enrolling patients and will be conducted across three dosage cohorts.

The biotech nabbed $40 million in a public offering in March last year.

Tune Therapeutics

• Therapeutic candidate: TUNE-401
• Technology: epigenetics
• Recent funding: $175 million series C

While Precision Biosciences is involved in genetic engineering to alter DNA, Tune Therapeutics, based in North Carolina and Washington, is on a mission to modify gene expression, but without changing the DNA. 

The company candidate TUNE-401 is poised to be the first epigenetic therapy to hit the clinic to treat HBV infections. The investigational drug silences viral HBV intDNA and cccDNA after employing LNPs to deliver RNA that targets HBV in the liver, which is being supplied by Canadian company Acuitas Therapeutics. Turning off the viral genetic material is intended to shut down viral transcription and suppress the production of new viral particles.

The biotech unveiled preclinical data where TUNE-401 showed strong and durable effects in targeted hepatocytes. 

It recently won clinical trial application (CTA) approval from the New Zealand Medicines and Medical Devices Safety Authority (Medsafe) to conduct phase 1b trials soon. Moreover, in Hong Kong, it received the Certificate for Clinical Trial from the Department of Health to enter phase 1b trials.

The American biotech was awarded $175 million in a series C round to propel its growing epigenetics pipeline in January.

Vir Biotechnology

• Therapeutic candidates: tobevibart and elebsiran
• Technology: antibody and siRNA
• Recent funding: $50 million grant

The likelihood of curing HBV infections with currently approved treatment is 3%-7%. California-based Vir Biotechnology wants to improve these chances at a much higher rate. That’s why it is evaluating a combination of regimens – antivirals and immunomodulators – including its antibody tobevibart and siRNA elebsiran. An ongoing phase 2b trial is testing tobevibart and elebsiran together to identify whether the duo can cure the disease. Some of the studies include the recombinant interferon immunotherapy peginterferon alpha, as part of the regimen.

Vir is looking to decrease the risk of developing end-stage liver disease complications like the progression to cirrhosis, liver transplant, and even death. 

The U.S.-based biotech last received funds in 2023 when it was allocated $50 million for Project NextGen, an initiative by the U.S. Department of Health and Human Services (HHS) to support the development of its COVID-19 candidate.

HBV therapeutic market to hit 4.9 billion in 2034

At present, there are no cures to treat HBV infections, which is what the above-mentioned biotechs are committed to addressing, but current standards of care focus on preventing new infections with the help of vaccinations as well as managing symptoms.

Chronic HBV is managed with antiviral medications, such as tenofovir and entecavir, to suppress the virus and reduce the risk of liver damage and complications. Interferon drugs like peginterferon trigger the immune system to fight hepatitis infections.

Big pharma companies like GSK are also interested in combating chronic hepatitis B. The British pharma giant has snapped up the rights to Ionis Pharmaceuticals’ drug bepirovirsen, an antisense oligonucleotide that is designed to minimize HBV replication. Now in phase 3 trials, the drug is en route to FDA approval, and GSK has all hands on deck to potentially bring bepirovirsen to the HBV market, which is expected to be worth 4.9 billion in nine years.