Background: IM156 is a novel oral potent biguanide, which has anticancer activity through AMPK activation and reduction of oxidative phosphorylation. Inhibition of oxidative phosphorylation (OXPHOS) is detrimental to OXPHOS dependent cancer cells, which are prone to energy stress. Preclinical experiments demonstrated that IM156 can be effective in glioblastoma, gastric cancer and other solid tumors. 

Methods: This is an open label, first-in-human, single center, dose-escalation study (NCT03272256) using the 3+3 design to determine the maximum tolerated dose and/or recommended phase 2 dose, dose limiting toxicities (DLT), safety, pharmacokinetics, pharmacodynamics and preliminary signals of anticancer efficacy of IM156 in patients with advanced solid tumors. Eligible patients are adults with advanced solid tumors refractory to standard therapies with adequate performance status (ECOG <2) and organ function with measurable disease per RECIST 1.1 (or RANO for gliomas). IM156 is administered orally every other day starting on day 1 of each 28 days cycle.

Results: To date, 12 patients (gastric cancer, 5; endometrial cancer, 2; ovarian cancer, 2; other, 3) were enrolled to 4 dose levels (100mg to 800 mg orally every other day). There have been no DLTs or > other grade 3 treatment-related adverse events (AEs). Most frequent AEs included nausea (67% of patients), vomiting (17%), diarrhea (23%), insomnia (17%), epigastric and abdominal pain (17%), weakness (8%), neuropathy (8%) and fatigue (8%); however, there were all grade 1 except for four grade 2 episodes (nausea, 2; insomnia, 1; diarrhea, 1; epigastric pain, 1). Mild elevations (<5 mmol/L) in lactate levels were noted anecdotally. The best response was stable disease in 5 patients (gastric cancer, 2; ovarian cancer, 1; endometrial cancer, 1; colorectal, 1).  Pharmacokinetic studies demonstrated dose proportional increase in Cmax and AUC, which were approaching expected efficacious range. Observed terminal half-life supported possible change of the schedule to daily oral administration. Pharmacodynamic marker studies are on-going. 

Conclusion: IM156 has been well tolerated with manageable AE profile. The dose escalation continues with a planned change from every other day administration to daily dosing.

About the company’s lead product, IM156

IM156 is an orally administered small molecule from the biguanide class, and it is a potent oxidative phosphorylation (OXPHOS) inhibitor. IM156 is particularly promising in that it has the potential to treat not only drug resistant cancers, but also cancers with molecular signatures of sensitivity to OXPHOS inhibition. Resistant tumor cells are very sensitive to OXPHOS inhibition due to transformation to mitochondrial OXPHOS from glycolysis. IM156 has shown strong in-vitro and in-vivo efficacy in a number of solid cancers, including gastric and glioblastoma (GBM). The company initiated its Phase 1 clinical study for IM156 in September 2017.

About ImmunoMet Therapeutics

ImmunoMet Therapeutics, a private biotechnology company, is dedicated to developing innovative oncology products to improve the quality of life and make a meaningful difference in the lives of cancer patients. The company was founded in 2015 and is headquartered at JLABS in Houston. In addition to its lead program, IM156, ImmunoMet has an extensive biguanide library which is being developed to harness cellular metabolism to address diseases across multiple therapeutic areas. For more information about the company, please visit www.immunomet.com.