ARQ 092 is an investigational orally available, selective, pan-AKT inhibitor that potently inhibits AKT1, 2 and 3 isoforms. The drug is currently in phase 1b for oncology and phase 1 for Proteus syndrome, a rare over-growth disease, in a trial being conducted by the National Institutes of Health (NIH). Both trials are biomarker-driven and are focused on enrolling patients with the AKT1 mutation. We plan to initiate a company sponsored Phase 1/2 trial in overgrowth syndromes, including PROS (PIK3CA Rare Overgrowth Syndromes) and Proteus syndrome, in Q2 of 2017.
ARQ 092 has demonstrated inhibition of tumor growth and downstream AKT signaling, in vivo, in tumors whose growth is driven by these targets. Single agent activity with ARQ 092 was observed in phase 1a and phase 1b studies as well as reductions in expression levels of relevant biomarkers. Publications support AKT1 as a viable target in oncology and Proteus syndrome.
ARQ 092 suppresses the AKT pathway via two modes of action. First, by binding to the inactive form of AKT, ARQ 092 prevents membrane localization and full AKT activation. Second, ARQ 092 also directly inhibits the membrane associated active form of AKT.
The AKT1 mutation is believed to play a role in a number of cancers and over-growth diseases, such as Proteus syndrome and Overgrowth syndromes similar to PROS.
The AKT pathway when abnormally activated is implicated in multiple oncogenic processes such as cell proliferation and apoptosis. This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity, which has been linked to a variety of cancers as well as to select non-oncology indications. Pre-clinical research has demonstrated that ARQ 092 potently and selectively inhibits both the active and inactive forms of AKT.
A landmark discovery by researchers from the National Human Genome Research Institute demonstrated that a somatic mutation in the AKT1 oncogene, which carries the set of instructions to produce the AKT1 kinase, causes Proteus syndrome. A point mutation – a single-letter “misspelling” in the DNA of the genetic code — in the AKT1 gene activates the tissue growth characteristic of Proteus syndrome.