ClearB Therapeutics Advances CLB-4000 Therapeutic Vaccine for Chronic Hepatitis B After Positive Sentinel Safety Review
Key Insights
ClearB Therapeutics (search) announced positive sentinel safety data for CLB-4000 (search), a bivalent therapeutic vaccine targeting chronic hepatitis B (search), enabling full enrollment in their Phase 1b first-in-human study.
The therapeutic vaccine combines CLB-405 (search) and CLB-505 (search) proteins designed to over-represent clearance profile epitopes from functional cure patients, adjuvanted with the novel TQL-1055 saponin adjuvant.
The Phase 1b study evaluates repeated intramuscular administration of CLB-4000 (search) in noncirrhotic adults with chronic hepatitis B (search), with additional cohorts testing combination therapy with Peg-IFNα-2a (search).
ClearB Therapeutics (search) announced that positive safety data from the sentinel subject in their Phase 1b clinical study has enabled full enrollment to proceed for CLB-4000 (search), a therapeutic vaccine designed to drive functional cure in patients with chronic hepatitis B (search) (CHB) infection. The announcement marks a significant milestone for the clinical-stage biotechnology company's first-in-human evaluation of their novel therapeutic approach.
Novel Therapeutic Vaccine Design
CLB-4000 (search) represents a bivalent subunit therapeutic vaccine comprised of CLB-405 (search) and CLB-505 (search) proteins, adjuvanted with TQL-1055. The vaccine's design is based on proprietary insights derived from rare-event infection resolution in patients who achieved functional cure from CHB. CLB-405 and CLB-505 are variants of HBsAg specifically engineered to over-represent clearance profile epitopes identified from functional cure patients.
The vaccine utilizes TQL-1055, a novel, rationally designed, semi-synthetic saponin adjuvant licensed from Adjuvance Technologies (search), Inc. TQL-1055 is a semi-synthetic analogue of the QS-21 saponin adjuvant used in currently available vaccines, including the shingles vaccine. The adjuvant is designed to provide improved tolerability while maintaining the strong immune response characteristics of QS-21, having demonstrated favorable tolerability in a Phase 1 clinical trial.
Phase 1b Study Design and Objectives
The CLB-4000 (search)-1-001 Phase 1b study is an open-label, multicenter, multiple-dose trial designed to assess the safety and tolerability of repeated intramuscular administration of CLB-4000. The study enrolls noncirrhotic adults with CHB who are taking a stable dose of standard-of-care nucleoside analogues (NUCs) for viral suppression.
The vaccine is administered with fixed antigen amounts of 250 μg CLB-405 (search) and 250 μg CLB-505 (search), adjuvanted with multiple dose levels of TQL-1055. To further enhance immune and antiviral responses, additional cohorts will evaluate CLB-4000 (search) in combination with Peg-IFNα-2a (search).
Primary objectives focus on safety and tolerability of CLB-4000 (search) with or without Peg-IFNα-2a (search), while secondary objectives include evaluation of antiviral activities and immunological responses. Results are expected on a rolling basis starting in the second half of 2026.
Addressing Global Health Burden
The development of CLB-4000 (search) addresses a substantial global healthcare challenge. According to the World Health Organization, hepatitis B (search) is defined as a "potentially life-threatening liver infection caused by Hepatitis B virus (HBV)" and represents "a major global health problem" that "can cause chronic infection and puts people at high risk of death from cirrhosis (search) and liver cancer (search)."
The global burden is significant, with approximately 2 billion people infected with HBV and approximately 250 million living with CHB. Viral hepatitis ranks as the 7th leading cause of human death globally, while liver cancer (search) represents the 3rd most common cause of cancer-related death worldwide.
Company Leadership Perspective
"It is very exciting to evaluate our promising therapeutic vaccine, CLB-4000 (search) in first in human trials in CHB patients. We look forward to sharing emerging clinical data with the Hepatitis B (search) community as it becomes available," said Aileen Rubio, PhD, CEO of ClearB Therapeutics (search). "CHB infection remains a substantial global health care problem with a continued need for safe and effective therapies. We believe that CLB-4000 could become an important component of evolving CHB treatment regimens."
Company Background
ClearB Therapeutics (search) was co-founded in 2017 with Professor Stephen Locarnini and the Victoria Infectious Diseases Reference Laboratory in Melbourne, Australia. The company focuses on developing immune-based therapies designed to drive functional cure of hepatitis B (search) infection, with their work grounded in proprietary insights derived from rare-event infection resolution in patients with CHB.