NOUS-209

Our study shows that MSI and neoantigen accumulation emerge during the evolution of precancerous lesions in LS. These findings support the clinical evaluation of Nous-209, a shared neoantigen vaccine, as an immunoprevention strategy for MSI-driven colorectal carcinogenesis, with important implications for cancer prevention research.

Immunogenic FSPs were found in independent datasets of LS MSI colorectal precancers and cancers. These results highlight Nous-209 ability to efficiently stimulate immunity against neoantigens in LS, supporting its development for cancer interception (ClinicalTrials.gov identifier: NCT05078866 ).

These findings demonstrated that NOUS-209 FSMs are present in both CRCs and UCs in LS, expanding the therapeutic potential of NOUS-209 beyond CRC. Moreover, the emergence of novel targetable FSMs in metachronous tumors suggests that NOUS-209 immunotherapy may be effective in the prevention of both primary and metachronous LS-associated cancers.

P1/2, N=45, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Sep 2026

P1/2, N=45, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2026 --> Sep 2025

P1/2, N=44, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2025 --> Jul 2026

P1/2, N=115, Active, not recruiting, Nouscom SRL | Trial primary completion date: Apr 2025 --> Oct 2026

P1/2, N=44, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P1/2, N=60, Recruiting, National Cancer Institute (NCI) | Active, not recruiting --> Recruiting | Trial primary completion date: Jul 2025 --> Mar 2025

A high coverage emerged from the comparative analysis of the EC FSPs with the content of the previously validated NOUS-209 vaccine. We obtained pieces of evidence of FSPs translation as expressed proteins from Ribo-seq, supporting the potential as the target of vaccination. The development of a nAgs-based vaccine strategy in MMRd EC may be further explored.

P1/2, N=115, Active, not recruiting, Nouscom SRL | Recruiting --> Active, not recruiting | Trial completion date: Jul 2026 --> Nov 2026

P1/2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting