Pharmaceutical Testing and Development


C188-9 STAT3 Inhibitor – Technology Overview

C188-9 STAT3 Inhibitor – Technology Overview StemMed’s unique capabilities center on its drug asset, C188-9, an oral STAT3 inhibitor identified using a unique computer-based, candidate-screening strategy that evaluated 920,000 compounds. Identification of highly promising hits was followed by a robust hit-to-lead process that included 2-D similarity screening, 3-D pharmacophore analysis, and 2 rounds of medicinal chemistry informed by structure-activity relationship (SAR) analysis. C188-9 binds to STAT3 with high affinity (4.7 nM), is selective for STAT3 among signaling molecules within cells activated by interleukin-6, has no toxicity in rats or dogs, has no unexpected effects on T cell immunity in mice, is highly effective in preventing or reversing tumor growth or manifestations of disease in all pre-clinical models tested in which genetic targeting of STAT3 was shown to be of benefit, and demonstrates high oral bioavailability (78% of an intravenously administered dose). C188-9 safety and oral bioavailability predict that the first dose level tested in patients will achieve plasma concentrations that effectively hit target.

In addition to its use in cancer patients, C188-9 has promise for treatment of a wide range of chronic inflammatory and fibrosing diseases. Also, in addition to oral and intravenous formulations, identification of a C188-9 prodrug provides additional opportunities for multi-tiered pricing across several cancer and non-cancer clinical applications, including patients with cachexia secondary to cancer or chronic kidney disease, as well as in patients with chemotherapy-induced neuropathy, idiopathic pulmonary fibrosis, scleroderma, inflammatory bowel disease, asthma, or immediate-type hypersensitivity reactions.