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Cancer Metabolism and Drug Resistance

Cancer Metabolism Program aimed to address cancer relapse with our lead compound IM156

In many types of cancers, drug-resistant cells arising after treatment with a targeted therapy or chemotherapy drug show a metabolic profile that is distinct from the susceptible cells. Rapidly growing cancer cells that are sensitive to current therapies typically show enhanced activity of glucose uptake and glycolytic degradation of glucose to lactate to support their energy and biosynthetic needs. In contrast, the resistant subpopulations arising from many therapeutic treatments are slow growers that are highly dependent on mitochondrial metabolic activities - Krebs cycle and oxidative phosphorylation (OXPHOS) – for their biosynthetic and bioenergetic needs. These resistant cells harbor a greater ability to metastasize and initiate tumors, and therefore, eradicating the resistant subpopulations is a crucial aspect of modern anti-cancer drug development. The resistant population’s dependence on mitochondrial metabolic activities makes it highly susceptible to the metabolic regulators targeting OXPHOS, and the combination of OXPHOS regulators has been proven to be an effective treatment option in suppressing the recurrence of cancers in a wide variety of preclinical studies. The goal of ImmunoMet’s Cancer Metabolism Program is to develop novel small compounds that selectively kill the resistant subpopulations by targeting their unique metabolic activities and to combine our drugs with current therapies to suppress cancer relapse.

IM156

IM156 is an orally administered small molecule from the biguanide class, and it is a potent OXPHOS inhibitor. IM156 is particularly promising in that it has the potential to treat not only drug resistant cancer, but also cancers with molecular signature of sensitivity to OXPHOS inhibition. IM156 has shown strong in vitro and in vivo efficacy in certain cancers, including Gliobastoma (GBM). IM156 is an orally administered small molecule from the biguanide class. IM156 entered phase 1 trial, a dose escalation study designed to evaluate the safety and tolerability of IM156 in patients with solid tumors. The primary endpoints of the study are to determine the maximum therapeutic dose and the randomized Phase 2 study dose.

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