ImmuNovation has produced endotoxin-free TNM prototypes with different bioactive molecules, which show formulation versatility and technical reproducibility. These formulations were able to incorporate both MHC I and MHC II peptides discovered using our CEACAM5-positive 3D models of colorectal cancer and PDAC, in combination with CpG adjuvant and PD-L1 siRNA for immune checkpoint modulation.
In vivo toxicology studies confirmed the biocompatibility and safety of all TNM formulations. No systemic toxicity or adverse immune effects were observed, which is important for the progression of studies toward validated IND-enabling studies.
Biodistribution studies confirmed the recognition and extensive uptake of TNM by antigen-presenting cells (APC), particularly dendritic cells, both in peripheral tissues and lymph nodes, demonstrating TNM's capability to accumulate in immunologically relevant sites.
Comparative studies demonstrated that TNM resensitized CEACAM5-positive tumors to immune checkpoint therapy (ICT) and conventional chemotherapy, outperforming the effect of these clinically relevant solutions as monotherapies. This in vivo preclinical data was validated using patient-derived peripheral blood mononuclear cells and 3D-bioprinted CEACAM5+ GI tumor models.
An extensive FTO analysis did not identify major blocking patents, confirming an FTO in the fields of nanovaccines and immunotherapies, and thereby providing a solid basis for further development and licensing.
A targeted IPR strategy was defined and implemented. A patent application (WO2020136657A9) covering the TNM composition and its specific use for CEACAM5+ GI cancers has been filed, which is now published. IP position and licensing terms, in addition to regulatory awareness, and a roadmap are now strengthened, supporting future start-up incorporation and potential public and/or investors’ engagement.
Stakeholder mapping was performed, and several exploratory meetings were held with pharmaceutical and biotech companies. A collaboration protocol has been signed with a leading CDMO, and a manufacturing contract was finalized to pursue the TNM production process development feasibility studies and scale-up under GLP and GMP-like conditions, which constitutes a major step toward clinical translation with funds awarded by the EIC Transition grant.
Of note, the results obtained through this project, including the market analysis and business development plan, supported the development of the new application entitled TIMNano to the European Innovation Council (EIC) Transition program, which has been recently awarded to further support TNM development and scale-up costs under GLP and GMP-like settings and first-in-human clinical trial design to confirm TNM safety and tolerability in patients affected with CEACAM5-positive tumors, namely CRC and PDAC.
