Cylene Looks to Horizon to Identify Genetic Basis of Response to Oral Anticancer Drug

Horizon Discovery is teaming up with Cylene Pharmaceuticals on a project that aims to identify genetic indicators of response to the latter’s early clinical-stage oral CK2 inhibitor, CX-4945. Cylene started a Phase I trial with the drug in September, in patients with multiple myeloma.

The collaboration will exploit Horizon’s X-MAN™ human isogenic cancer cell lines to identify genetic factors in cancer that determine the greatest sensitivity to CX-4945. The firms hope this approach will lead to reduced development times and greater success in clinical trials. “CX-4945 is the first drug in the clinic that targets the kinase CK2, a protein that is overexpressed in many diverse cancers,” explains Kenna Anderes, Ph.D., executive vp of cancer biology at Cylene. “Successful exploitation of this novel molecular target to treat cancers absolutely requires an understanding of the genetic mutations and molecular pathways to which the tumor has become reliant, i.e., the context of vulnerability.”

Horizon claims CX-4945 is an ideal candidate to which its X-MAN panel of over 250 genetically defined human cell lines can be applied. “There is now an abundance of information on how cancer arises and progresses and we also know that onset, progression, and response to drugs is substantially different from one patient to another,” remarks Chris Torrance, Ph.D., Horizon CEO. “The old one-size-fits-all approach to cancer drug development and prescription will need to move towards a more targeted, or personalized paradigm.”

Cylene is exploiting two separate discovery platforms to identify new anticancer drugs. One creates first-in-class inhibitors of serine/threonine protein kinases, while the other generates RNA polymerase I (Pol I) targeting agents. The RNA polymerase I platform has led to the development of Cyclene’s lead compound, Quarfloxin (CX-3543), which is currently undergoing Phase II evaluation for the treatment of carcinoid/neuroendocrine tumors (C/NET). Derived from the fluoroquinolone drug class, Quarfloxin disrupts a protein-DNA complex in the abnormal nucleolus of cancer cells, which selectively causes cell death by knocking out a critical source of support for tumor cells, the firm claims.

CX-4945 originates from Cylene’s serine/threonine kinase inhibitor platform, and is the first agent in its class to enter clinical development, Cylene points out. The drug has been designed as a multifunctional inhibitor that targets a single protein and could have potential applications against many cancers. The firm’s preclinical pipeline includes additional PIM kinase inhibitors and RNA Pol 1 inhibitors for the potential treatment of cancer, and a CK2 inhibitor for the potential treatment of pain.