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

ended

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. 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. Fewer synthetic steps and a reduced need for costly and hard-to-find intermediates 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. In addition, our novel S-CAMs have an effective dose in the lower pM range, making these new molecules ultrapotent. 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.