DO-1

DO-1 is a highly selective small molecule inhibitor of the MET kinase that was found to inhibit the organic cation transporter-2 (OCT-2).

DO-1 (formerly JNJ-38877618 or OMO-1) was initially tested in a healthy volunteer study where initial data on pharmacokinetics, food effect and safety were obtained by JNJ where it originated.

The formation of a MET inactive metabolite that remained in circulation was noted in this study, but associated adverse events were not observed.

A phase 1/1b patient study carried out by OCTIMET, who licensed OMO-1 from JNJ, led to the identification of a recommended Phase 2 Dose (250mg BID). Promising signs of clinical activity were observed in MET exon 14 skipping patients as well tumour shrinkage in combination with an EGFR inhibitor (gefitinib) in a gefitinib resistant patient.

Preclinical data generated at DeuterOncology have shown that, in addition to MET target inhibition, DO-1 is able to induce vascular normalisation, reduce tumour acidification and increase DNA adduct formation in combination with chemotherapeutics such as gemcitabine and cisplatin.