Our Science
NETRIS Pharma Innovative Concept
A scientifically-driven approach against cancer: cancer as the resurgence of embryonic development processes.
The development of cancer and tumor cells is increasingly perceived by leading scientific researchers as the reactivation of several embryonic development programmes. Along this hypothesis, netrin-1, a laminin related protein, known to have a critical role in neuronal guidance during embryogenesis, is not expressed in healthy adult tissues but is re-expressed in the large majority of human cancers. The up-regulation of netrin-1 in the tumor microenvironment is associated with tumor cell survival, Epithelial-to-Mesenchymal transition (EMT), enhanced tumor heterogeneity and metastatic development.
Focus on Oncology
In a large fraction of cancers, certain embryonic molecules such as netrin-1 provide selective tumoral advantage, both for cancer cell survival and cancer cell plasticity potentiation. As a result, tumor cells escape most of the current approved therapies. NETRIS Pharma lead asset NP137 targeting NETRIN-1 not only induces tumor cells death but also prevents the plasticity of these cells towards a more mesenchymal phenotype, known to induce resistance these therapies.
Therapeutic strategy: NETRIS Pharma’s lead asset induces cancer cell death and reduces tumor plasticity, thereby alleviating resistance to chemotherapies, targeted therapies and immunotherapies.
Most anti-cancer therapies currently available are targeting highly proliferative cancer cells. However, the past decade has shown that resistance to these therapies is intrinsically linked to the ability of a subset of cancer cells to escape these treatments through phenotypic changes. The therapeutic strategy of NETRIS Pharma is to develop novel drugs inhibiting cancer plasticity in order to inhibit tumoral progression and also potentiate long term efficacy of chemotherapies, targeted therapies and immunotherapies. NETRIS Pharma lead asset is designed to block the interaction between netrin-1 and its receptors to both restore cell death and inhibit phenotypic plasticity (Lengrand et al., Nature 2023). This strategy has been validated through an extensive set of preclinical experiments and confirmed by the positive outcome of the Phase 1 clinical trial assessing NETRIS Pharma lead asset NP137 in patients with advanced solid tumors. More than 250 patients have been exposed to NP137 and the first clinical outcomes are published (Cassier et al., Nature 2023).
Physiological
context
pro-apoptotic mechanism
Pathological
context
anti-apoptotic mechanism
Therapeutic
context
restoration of the pro-apoptotic mechanism
