ClearB Therapeutics, Inc., a clinical-stage biotechnology company dedicated to developing therapies aimed at achieving functional cure in patients with chronic hepatitis B (CHB) infection, announced that the sentinel subject safety review in their ongoing Phase 1b study of CLB-4000 supports enrollment of the remaining cohort. This milestone allows the trial to proceed with confidence in evaluating the safety and potential efficacy of the company’s therapeutic vaccine.
CLB-4000: A Next-Generation Therapeutic Vaccine
CLB-4000 is a bivalent subunit therapeutic vaccine composed of CLB-405 and CLB-505 proteins, combined with the novel adjuvant TQL-1055. Both CLB-405 and CLB-505 are variants of hepatitis B surface antigen (HBsAg) engineered to over-represent epitopes associated with viral clearance observed in patients achieving functional cure. TQL-1055, licensed from Adjuvance Technologies, Inc., is a rationally designed, semi-synthetic saponin adjuvant intended to enhance immune responses, supporting the vaccine’s therapeutic potential.
The Phase 1b study, designated CLB-4000-1-001, is an open-label, multicenter, multiple-dose trial designed to evaluate the safety and tolerability of repeated intramuscular administration of CLB-4000. Each dose contains 250 μg of CLB-405 and 250 μg of CLB-505, adjuvanted with varying dose levels of TQL-1055. Participants are non-cirrhotic adults with CHB who are on a stable nucleos(t)ide analogue (NUC) therapy for viral suppression.
In addition to the primary focus on safety, additional cohorts will explore the combination of CLB-4000 with Pegylated Interferon alpha-2a (Peg-IFNα-2a) to assess whether this combination further boosts antiviral and immune responses. The study’s primary objectives include safety and tolerability of CLB-4000 with or without Peg-IFNα-2a, while secondary objectives encompass evaluation of antiviral activity and immunological responses. Preliminary results are expected to be reported on a rolling basis beginning in the second half of 2026.
Sentinel Safety Review Supports Expansion
The initial sentinel subject review is a critical step in first-in-human studies. ClearB’s review confirmed that CLB-4000 was well-tolerated in the sentinel participant, supporting the safe enrollment of the remaining participants in the cohort. This milestone reflects the careful design and monitoring protocols implemented by the company to ensure patient safety in early-stage clinical testing.
“This is an exciting moment for ClearB as we evaluate CLB-4000 in first-in-human trials for CHB patients,” said Aileen Rubio, PhD, CEO of ClearB Therapeutics. “We look forward to sharing emerging clinical data with the Hepatitis B community as it becomes available. Chronic hepatitis B remains a substantial global health challenge, and there is a continued need for safe, effective therapies. We believe CLB-4000 could become an important component of evolving CHB treatment regimens.”
Advancing Functional Cure Strategies
Chronic hepatitis B affects hundreds of millions of people worldwide and remains a leading cause of liver cirrhosis, hepatocellular carcinoma, and liver-related mortality. Current therapies, including nucleos(t)ide analogues, suppress viral replication but rarely achieve functional cure, defined as sustained loss of HBsAg with or without seroconversion.
CLB-4000 represents a next-generation therapeutic approach by stimulating the immune system to target HBV more effectively, aiming to induce functional cure in patients who are already virally suppressed with standard-of-care therapies. The inclusion of a novel adjuvant system and specifically designed antigen variants positions CLB-4000 as a potentially transformative therapy in the CHB landscape.
The study’s design also explores synergistic effects with Peg-IFNα-2a, a therapy known to enhance immune-mediated viral clearance. This combination approach reflects a growing consensus that multi-modal immunotherapy may be required to achieve higher rates of functional cure in CHB patients.
Looking Ahead
ClearB Therapeutics remains committed to developing CLB-4000 and advancing its therapeutic pipeline with a focus on safety, efficacy, and global patient impact. The successful sentinel review marks a key milestone in the company’s first-in-human trial, enabling continued enrollment and evaluation of CLB-4000 across multiple cohorts.
As the trial progresses, ClearB aims to generate early clinical evidence of antiviral activity and immune response, guiding subsequent development and combination strategies. With CHB remaining a global public health priority, CLB-4000 has the potential to become a critical new option for patients seeking functional cure, complementing existing antiviral therapies and contributing to broader efforts to eliminate hepatitis B worldwide.
By advancing innovative therapeutic vaccines like CLB-4000, ClearB Therapeutics is at the forefront of immunotherapy research, working to transform the standard of care for CHB patients and address one of the most persistent challenges in global liver health.
About Hepatitis B
The World Health Organization defines hepatitis B as a “potentially life-threatening liver infection caused by Hepatitis B virus (HBV). It is a major global health problem. It can cause chronic infection and puts people at high risk of death from cirrhosis and liver cancer.” Approximately 2 billion people are infected with HBV and ~250 million living with CHB. Viral hepatitis is the 7th ranked cause of human death and liver cancer is the 3rd most common cause of cancer related death globally.
