Spirocyclic CAMs as novel and ultrapotent anti-HBV drugs (S-CAM)

Introduction

This PoC project aims to advance the development of next-generation direct-acting antivirals (DAAs) against hepatitis B virus (HBV), namely capsid assembly modulators (CAMs) with a novel spirocyclic scaffold chemotype described in our proprietary patent (WO2021/160617). The identification of next-generation spirocyclic CAMs (S-CAMs) during the funding period of ERC CoG 725038 (FATE) represents a potentially important step towards the cure of chronic HBV infection, one of the major uncontrolled medical challenges of our time with a huge economic and social burden worldwide.

Advantages of the Novel Scaffold

The novel spirocyclic scaffold represents a major advantage for the progression towards the clinic, thanks to its greatly improved synthetic process and excellent stability in mouse and human hepatocytes.

Cost-Effective Production

• Fewer synthetic steps
• Reduced need for costly and hard-to-find intermediates

These factors provide a price-competitive production process compared to any other CAM, such as our previous generation non-spirocyclic series (patent WO2020/234483) sold to a US-based biotech company.

Potency of S-CAMs

In addition, our novel S-CAMs have an effective dose in the lower pM range, making these new molecules ultrapotent.

Project Objectives

In this project, we will confirm the technical and commercial viability of the ultrapotent novel S-CAMs that are called to out-compete previous generation non-spirocyclic series still in preclinical and first clinical phases as follows:

1. Evaluate the pharmacological properties of the best candidates in normal inbred mice and assess their safety, efficacy, and immunostimulatory potential in HBV-replicating transgenic mice.
2. Perform a comparative analysis of the main competing CAM solutions.
3. Establish the IP strategy and stakeholder mapping.
4. Prepare a business plan and commercialization roadmap for in-licensing to a spin-off and mid-term out-licensing to potential strategic partners to bring the best ultrapotent S-CAMs candidates to the market.