ERG Inhibitors

Targeting ETS gene fusions represents the “signature program” of OncoFusion. In 2005, it was discovered and published in Science by Dr. Chinnaiyan, a co-founder of the company, that approximately 50% of prostate cancers harbor a recurrent gene fusion of the androgen-regulated gene TMPRSS2 to the oncogenic ETS transcription factor, ERG. In addition to prostate cancer, ETS gene fusions also account for over 95% of Ewing’s sarcoma and a subset of Acute Myeloid Leukemias (AML).

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OncoFusion is in the forefront of developing small-molecule inhibitors against ERG. An early lead compound that has been identified is a 7-residue peptidomimetic that interacts specifically with a binding pocket in ERG. The inhibitory peptidomimetic (called RI-EIP) disrupts ERG’s binding to protein co-factors as well as its interaction with DNA.

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Preclinical studies in vitro and in vivo have demonstrated favorable strong on-target therapeutic efficacy of RI-EIP. Based on these findings, the founders were recently awarded a $1M grant from the Prostate Cancer Foundation to develop these compounds into drugs. A manuscript describing these findings is under revision at the journal Science. Lead optimization is underway to convert these peptidomimetics into drug-like non-peptide small-molecule inhibitors.

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