Periodic Reporting for period 1 - S-CAM (Spirocyclic CAMs as novel and ultrapotent anti-HBV drugs (S-CAM))
Reporting period: 2023-10-01 to 2025-03-31
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.
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.
Over the course of the project, we conducted an extensive preclinical evaluation of three top-performing CAM candidates. Based on pharmacokinetics, metabolic stability, and antiviral potency, one lead compound—SR-1804—was selected for further development.
We performed detailed pharmacological assessments, including bioavailability, liver distribution, and safety studies, in both oral and intravenous formulations. In mouse models of HBV infection, SR-1804 demonstrated strong antiviral effects without observable toxicity. Mechanistic studies confirmed capsid destabilization as the mode of action and revealed an additional benefit in promoting antiviral immune responses.
These results support the therapeutic potential of our lead molecule and justify its advancement toward translational development. A dedicated commercialization strategy is underway, including engagement with potential industrial partners and preparations for follow-up funding and regulatory steps.
We performed detailed pharmacological assessments, including bioavailability, liver distribution, and safety studies, in both oral and intravenous formulations. In mouse models of HBV infection, SR-1804 demonstrated strong antiviral effects without observable toxicity. Mechanistic studies confirmed capsid destabilization as the mode of action and revealed an additional benefit in promoting antiviral immune responses.
These results support the therapeutic potential of our lead molecule and justify its advancement toward translational development. A dedicated commercialization strategy is underway, including engagement with potential industrial partners and preparations for follow-up funding and regulatory steps.
Our findings establish SR-1804 as a best-in-class candidate in the CAM category, with superior potency, safety, and synthetic accessibility compared to existing compounds. Its demonstrated ability to disrupt HBV replication and boost immune responses highlights a novel and multifaceted mechanism of action.
To facilitate further development, we are compiling all preclinical data—including analogs and derivative compounds—into a comprehensive intellectual property package. This will support a two-pronged exploitation strategy: either licensing to an external pharmaceutical partner or development via an academic spin-off.
Together with our institutional technology transfer and business development offices, we are finalizing a commercialization plan that includes a refined business model, stakeholder engagement roadmap, and plans for further confirmatory studies. These efforts aim to bridge the gap between discovery and patient access by enabling clinical development of the first curative therapy for chronic hepatitis B.
To facilitate further development, we are compiling all preclinical data—including analogs and derivative compounds—into a comprehensive intellectual property package. This will support a two-pronged exploitation strategy: either licensing to an external pharmaceutical partner or development via an academic spin-off.
Together with our institutional technology transfer and business development offices, we are finalizing a commercialization plan that includes a refined business model, stakeholder engagement roadmap, and plans for further confirmatory studies. These efforts aim to bridge the gap between discovery and patient access by enabling clinical development of the first curative therapy for chronic hepatitis B.