Preclinical Discovery Programs

When a target has been selected and chemical matter obtained, our multidisciplinary team works to optimize the compound’s drug-like properties, refine its anticancer effects, and drive the compound toward clinical development. Our experience and platform have led to a rich pipeline of discovery programs targeting several classes of epigenetic modulators. This includes multiple histone methyltransferase (HMT), histone acetyltransferase (HAT), and helicase inhibitor programs.

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SETD2 Inhibitor Program

SETD2 is a histone methyltransferase that catalyzes the deposition of the third or final methyl group onto a histone tail, resulting in H3K36 tri-methyl marks in chromatin. Histones are multi-subunit proteins wrapped by DNA and the methyl marks that SETD2 catalyzes act to regulate gene expression and other DNA functions. Dysregulation of this activity has been shown to lead to the development of certain hematologic malignancies, including multiple myeloma.

We have discovered a potent, selective, oral, small molecule SETD2 inhibitor and generated preclinical data demonstrating that SETD2 is an oncogenic driver in t(4;14) multiple myeloma. SETD2 inhibition has led to potent in vitro and in vivo growth inhibition in both the high risk t(4;14), as well as, non-t(4;14) multiple myeloma cell lines, suggesting the potential for broad therapeutic benefit in patients with multiple myeloma. In August 2021, we announced the Investigational New Drug application for our SETD2 inhibitor, EZM0414 received clearance from the U.S. FDA, and we expect to initiate a first-in-human clinical trial later this year.

Click here to access our preclinical publications and presentations.