C3*
mRNA-Based Therapeutic Vaccine for Functional Cure of Chronic Hepatitis B
Dr Maria Jose Limeres, University Medical Center Mainz; Dr German Islan, University Medical Center Mainz; Prof. Stephan Gehring, University Medical Center Mainz; Dr Maximiliano Cacicedo, University Medical Center Mainz
Innovectis
Challenge
Chronic hepatitis B (CHB) affects 254 million people worldwide, causing over 1 million deaths annually from cirrhosis and hepatocellular carcinoma. Current nucleoside analogue therapies suppress viral replication but achieve functional cure rates of less than 1% annually, comparable to spontaneous clearance. Pegylated interferon offers marginally better outcomes (5-11%) but with significant side effects and limited applicability. No approved therapy addresses the fundamental challenge: restoring immune control to achieve sustained HBsAg loss and durable functional cure without lifelong treatment.
Technology
We developed a bivalent mRNA-based therapeutic vaccine encoding both hepatitis B surface antigen (HBsAg) and core antigen (HBcAg). This dual-antigen approach activates complementary immune mechanisms: HBsAg induces neutralizing antibodies for viral clearance, while HBcAg stimulates potent CD8+ T-cell responses essential for eliminating infected hepatocytes. Our signal peptide optimization approach enhances MHC class I presentation, achieving 3-fold higher CD8+ T-cell activation versus unmodified constructs. In chronic HBV mouse models, our vaccine achieves more than 90% functional cure rates with sustained HBsAg clearance maintained beyond 73 days, substantially exceeding competitor approaches (16-25%).
Commercial Opportunity
The CHB therapeutic market is projected to reach €6.5 billion by 2031, driven by unmet need for functional cure therapies. Our target population includes 33.5 million diagnosed patients globally, with 6.6 million in premium markets (EU/US/Japan). Pricing strategy: €10,000/treatment in developed markets. Business model: Development through Phase II proof-of-concept, followed by licensing to major pharmaceutical partner. Comparable CHB therapeutic deals range €500M-1B total value. Exit timeline: 5-6 years to licensing milestone.
Development Status
Preclinical validation completed: efficacy demonstrated in AAV-HBV and HBV-transgenic mouse models showing sustained HBsAg clearance, HBV DNA suppression below LLOQ, and robust T-cell responses. Currently preparing IND-enabling GLP toxicology studies (single-dose and repeat-dose in rats) and biodistribution studies. Regulatory engagement with Paul-Ehrlich-Institut (PEI) Scientific Advice Meeting planned for 2027. Applied to non-dilutive funding: EXIST Research Transfer (pending). Team includes experienced hepatology researchers, and regulatory advisors.
Patent Situation
The key element of the technology is the optimized mRNA design and a specific signal peptide that significantly enhances antigen cross-presentation via MHC class I molecules, resulting in a threefold increase in the HBV-specific CD8+ T-cell response. The invention is protected by a patent family (US and PCT patent application, pending) jointly owned by UM and the University of Pennsylvania. The two institutions have entered into an agreement stipulating that UM holds the lead in conducting the patent proceedings and licensing.
Further Reading
mRNA-LNP vaccines against hepatitis B virus induce protective immune responses in preventive and chronic mouse challenge models (2025). María José Limeres, Rocio Gambaro, Malin Svensson, Silvia Fraude-El Ghazi, Leah Pretsch, Daniel Frank, German A. Islan, Ignacio Rivero Berti, Matthias Bros, Ying K. Tam, Hiromi Muramatsu, Norbert Pardi, Stephan Gehring, Maximiliano L. Cacicedo. Molecular Therapy 33 (9) 4156-4174 doi.org/10.1016/j.ymthe.2025.06.027
