IM156 Tumor Metabolism
and Drug Resistance
Tumor Metabolism Program Aimed to Address Cancer Relapse with our Lead Compound IM156
IM156 is an orally administered small molecule from the biguanide class. IM156 is a particularly promising compound that has the potential to treat drug resistant tumors. IM156 has shown strong in vitro and in vivo efficacy in certain cancers, including gastric, lymphoma, lung, breast and gliobastoma. A Phase 1 clinical study has been completed with IM156. The trial was a dose escalation study designed to evaluate the safety and tolerability of IM156 in patients with solid tumors. IM156 is the first Protein Complex 1 Inhibitor to successfully a complete Phase 1 study and generate a recommended Phase 2 dose.
Targeting Tumor Metabolism
In many types of tumors, 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 tumor 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 tumors in a wide variety of preclinical studies. The goal of ImmunoMet’s tumor metabolism program is to develop novel small molecules that selectively kill the resistant subpopulations by targeting their unique metabolic activities and to combine our drugs with current therapies to suppress tumor relapse.
IM156: The Promise of a Safe and More Potent Therapy
IM156 is a potent OXPHOS inhibitor designed to enhance the beneficial effects of biguanides. One of the most well-known biguanides is metformin, which is used in diabetes treatment and has been on the market for over 40 years. Empirical evidence has shown that biguanides target tumor metabolism, although metformin shows a weak effect due to its lower potency. Phenformin showed strong preclinical efficacy in multiple models but the product was removed from the market due to toxicity. At ImmunoMet, we are developing new biguanides optimized for oncology and OXPHOS-dependent metabolism, including IM156, with high potency and good safety and thus a broader therapeutic window.
