Science behind our technology

Frezent addresses the problem of residual disease by targeting non-dividing dormant cancer cells.

Dormant cancer cells metabolism

Dormant cancer cells are resistant to treatments and pose risk of recurrence. The dormant state is sustained through metabolic adaptation and epithelial-mesenchymal transition (EMT, a stem-cell-like state). Frezent’s strategy is focused on lipid metabolism. Fatty acid oxidaiton and sphingolipod metabolism are central pathways that support energy production (NADPH) and supply metabolites and signaling molecules that fuel tumorigenisis (Acetyl-CoA, S1P).

Dormant cancer cells rely on lipids for energy and survival

We develop first-in-class therapeutics that eliminate cancer cells by targeting their distinct metabolic vulnerabilities.

Frezent interrupts lipid metabolism, leading to buildup of ceramide lipid and free fatty acid, and consecutively lipotoxic stress and apoptosis.

Dividing cancer cells also engage lipid metabolism for rapid membrane synthesis during cell division, and for activating JAK-STAT and PI3K/AKT oncogenic pathways. Since lipid metabolism and kinase pathways are intertwined, Frezent’s lipid metabolic blockade could be effectively combined with selective kinase inhibitors, to enhance effect of the treatment against dividing cancer cells.

Therapeutic Programs

Metablolic enzymes are secreted into tumor microenvironment (TME) by the supporting cells and are transported to cancer cells to sustain their metabolic needs. We develop first-in-class monoclonal antibodies binding to the secreted metabolic enzymes in the TME. Antibody-enzyme complext makes the enzyme inactive and causes metabolic blockade inside cancer cells.

The strategy of capturing soluble enzymes outside of cancer cells using antibodies to induce intracellular cytotoxic effect is unique and offers safety for normal cells, that do not rely on extracellular transport of the metabolic enzymes.

Neutralizing Monoclonal Antibodies Program

Antibody-drug conjugate (ADC) Program

Antibody-Drug Conjugates (ADC) combines cancer specific antibody linked to a chemical inhibitor (payload). Binding of the antibody to the cancer specific receptor triggers transport of the ADC into cancer cells and release of the payload, followed by cytotoxic cell death.

Frezent discovered a specific receptor that is present on the surface of both dividing and non-dividing cancer cells. We developed a proprietary antibody targeting this receptor, and now in the process of screening metabolic inhibitors that will become ADC payloads, tailored for specific cancers. This approach will overcome the limitations of existing payloads that are designed to act only against actively dividing cancer cells, and leave behind non-dividing (dormant) cancer cells.

Our pipeline

Scientific Publications

  1. Cheng, H., Wang, M., Su, J., Li, Y., Long, J., Chu, J., Wan, X., Cao, Y., & Li, Q. (2022). Lipid metabolism and cancer. Life, 12(6), 784. https://doi.org/10.3390/life12060784

  2. Endo, H., & Inoue, M. (2018). Dormancy in cancer. Cancer Science, 110(2), 474–480. https://doi.org/10.1111/cas.1391

  3. Giancotti, F. G. (2013). Mechanisms governing metastatic dormancy and reactivation. Cell, 155(4), 750–764. https://doi.org/10.1016/j.cell.2013.10.029

  4. Linde, N., Fluegen, G., & Aguirre-Ghiso, J. (2016). The relationship between dormant cancer cells and their microenvironment. Advances in Cancer Research, 132, 45–71. https://doi.org/10.1016/bs.acr.2016.07.002

  5. Recasens, A., & Munoz, L. (2019b). Targeting cancer cell dormancy. Trends in Pharmacological Sciences, 40(2), 128–141. https://doi.org/10.1016/j.tips.2018.12.004

  6. Song, K., Wang, J., & Huang, D. (2023). Therapy-induced senescent tumor cells in cancer relapse. Journal of the National Cancer Center, 3(4), 273–278. https://doi.org/10.1016/j.jncc.2023.09.001