Chronic hepatitis B virus (HBV) infection remains one of the world’s most pressing yet unresolved health challenges. Over 290 million people are chronically infected, and nearly 850,000 die annually from complications such as liver cirrhosis and liver cancer, according to the World Health Organization. Despite the availability of effective vaccines and antiviral drugs, current treatments for chronic hepatitis B (CHB) rarely lead to a cure and typically require lifelong administration, placing a heavy burden on patients and healthcare systems—especially in regions like sub-Saharan Africa and Asia.
HBV persistence stems from its ability to escape immune detection and establish stable reservoirs in the liver. Existing antiviral therapies suppress viral replication but do not eliminate the viral genetic material (cccDNA), leaving the infection unresolved. Many promising therapeutic candidates have failed in development, and no curative options are currently available.
This project addresses the urgent need for curative therapies through the development of a new class of small molecules known as capsid assembly modulators (CAMs), which target the HBV core protein—a critical component of the viral life cycle. Unlike standard treatments that only suppress viral replication, CAMs interfere with viral capsid formation, attacking the virus at a key structural and functional level.
Building on the ERC-funded FATE project, we have discovered a new family of ultrapotent CAMs with a unique chemical scaffold. These compounds show exceptional antiviral activity, good oral bioavailability, and promising safety characteristics. Their improved molecular properties also make them more scalable for future clinical development.
The goal of this Proof of Concept project was to validate the therapeutic and commercial potential of these next-generation CAMs, referred to as S-CAMs. Specifically, we set out to:
• Demonstrate preclinical efficacy and safety in laboratory models;
• Optimize synthetic pathways to support scalable and cost-effective production;
• Assess the commercial feasibility of further development through venture funding and spin-off formation.
If successful, this strategy could revolutionize HBV therapy by offering a curative, short-duration treatment. The public health impact could be especially meaningful in high-prevalence regions, reducing both transmission and disease burden. In addition to medical benefits, the project aims to stimulate biotech innovation in Europe, foster public–private partnerships, and pave the way for future commercialization.
Moreover, the project incorporates socioeconomic and regulatory dimensions. Health economic modeling, public health perspectives, and ethical considerations are central to understanding how such therapies can be made accessible, accepted, and equitably distributed across global populations.
