“There’s a ceiling to cancer treatment. If the tumor microenvironment barrier can be normalized and ‘false resistance’ overcome, that ceiling can be broken.”
Cho Won-dong, chairman of Pentrym Biosciences, made the remarks at a global symposium held Sept. 14, saying, “If existing cancer drugs can reach cancer cells at therapeutically effective concentrations, we can break through the ceiling of cancer treatment.”
Pentrym attributes the failure of existing cancer drugs not only to genetic mutations in cancer cells but also to the tumor microenvironment (TME) surrounding them. The company defines as “false resistance” the phenomenon in which cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM) form a barrier that prevents cancer drugs and immune cells from adequately reaching cancer cells.
The company recently received U.S. Food and Drug Administration (FDA) approval to conduct a Phase 2 clinical trial in the United States, allowing it to move to the stage of testing this hypothesis in actual patients.
Choi Jin-ho, an emeritus professor at Dankook University and developer of the underlying technology, said, “The FDA’s approval of a Phase 2 trial combining Pentrym with existing cancer drugs goes beyond a simple administrative procedure,” adding, “It is significant because it elevates the new hypothesis of false resistance to the stage of being tested in patients.”
The company also unveiled preclinical research results involving various cancer drugs and cancer types. In a pancreatic cancer model, Pentrym combined with gemcitabine produced a 92% tumor-suppression effect, while in triple-negative breast cancer, the combination with paclitaxel produced a 40% tumor-suppression effect. In a non-small cell lung cancer model, no metastasis was observed when Pentrym was combined with bevacizumab.
In a recent study using patient-derived lung cancer organoids, the cancer-cell viability rate was 57.8% after treatment with the pan-RAS targeted cancer drug daraxonrasib, but rose to 89.6% when cancer-associated fibroblasts (CAFs) were co-cultured to create a false-resistance environment. When Pentrym was subsequently added while continuing daraxonrasib treatment, the rate fell to 7.5%.
Jin Geun-woo, co-CEO of Pentrym, said, “Existing cancer drugs have focused on targeting and killing cancer cells, while the tumor microenvironment has received relatively less attention.” He added, “We evaluated different classes of cancer drugs across multiple cancer models, but reached the same conclusion: targeting the surrounding environment while combining it with existing cancer drugs can produce a synergistic effect.”
Based on these findings, Pentrym plans to conduct clinical trials by maintaining existing cancer drugs rather than replacing them and adding Pentrym. The strategy uses two treatment axes: existing cancer drugs attack cancer cells, while Pentrym targets the tumor microenvironment that causes false resistance.
Lee Ji-eun, Pentrym’s head of global clinical development, said, “Typically, when cancer treatment is not working well, doctors switch cancer drugs, but our strategy is to maintain the existing cancer drug.” She added, “The principle of our global clinical trials is to add Pentrym so that two treatment axes operate simultaneously, attacking both cancer cells and false resistance.”
A prostate cancer clinical trial is currently underway in South Korea, while the company is preparing follow-up procedures for an FDA-approved Phase 2 trial in the United States. The company has designated 12 weeks after dosing as a key point for assessing early clinical signals and plans to evaluate safety and tolerability, biomarkers and radiographic tumor responses.
Lee said, “Twelve weeks is not the end of the trial but the point at which we can determine the first objective signal that we are actually breaking through the ceiling of cancer treatment.” She added, “Ultimately, reliable patient data is the most important factor in proving the hypothesis.”
