Science behind our technology

From metabolic plasticity to metabolic vulnerability

Metabolic and phenotypic plasticity allows cancer cells to survive under stressful conditions by transforming from actively dividing to non-dividing (dormant) and back to dividing cell state. Lipid metabolism plays a central role in this transformation.

Cancer cells rely heavily on lipid metabolism for membrane synthesis during rapid proliferation and for energy production.

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Lipids allow cancer cells to withstand the stress from anti-proliferative treatments.

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Lipids are also the main source of energy for the residual, non-dividing (dormant) cancer cells, that can survive after the drug therapy.

This metabolic adaptation and dependence on lipid metabolism also make cancer cells vulnerable to metabolic disruption, presenting an attractive therapeutic targeting opportunity.

Fatty Acid Oxidation (FAO) Drives Treatment Resistance

Resistant cells shift their energy source to break down fatty acids inside mitochondria, providing source of ATP energy during and following treatments.

Sphingolipid Metabolism Supports Survival and Promotes Drug resistance

Sphingolipid metabolism acts as survival rheostat, that governs a cancer cell ability to transition between an actively dividing state and a non-dividing drug-resistant dormant state.

Frezent’s therapeutics eliminate cancer cells by targeting their metabolic vulnerabilities.

By disrupting lipid metabolism we aim at blocking cancer cell division and preventing the survival of non-dividing, dormant cancer cells, residual after therapy.

Our Therapeutic Programs

Neutralizing Monoclonal Antibodies

Metablolic enzymes are secreted into tumor microenvironment 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.

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.

Antibody-Drug Conjugates (ADC)

ADCs 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