CK2 program
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Inhibitors of CK2 for Unprecedented Combinability
Protein Kinase CK2 Cancer Drug Target
CK2 is a protein kinase that regulates multiple oncogenic pathways including EGFR-regulated pathways, Akt and WNT signaling cascades, NF-κB transcription, angiogenesis, Hsp90 chaperone pathway and the DNA damage response. CK2 activity and levels are elevated in many cancers of diverse genetic background and this overexpression leads to a dependence on its continued expression and activity. Because CK2 is essential for cancer cell survival, is up-regulated in many different cancers and is not mutated, it is a cancer target ideally suited for the development of a dynamic combination agent. Cylene’s leadership in exploiting CK2 pathways for rational combination therapies identifies and enables numerous drug combinations for improved treatment outcomes.
Protein Kinase CK2 is essential for cancer cell survival by driving multiple pathways. When a CK2 inhibitor is combined with an agent that acts through one of these pathways, synergy is observed. Phase II trials are planned with agents that rely on the EGFR pathway (erlotinib) and DNA damage repair pathway (gemcitabine/carboplatin).
CX-4945
CX-4945 is a potent and selective inhibitor of CK2 to which Cylene owns all IP. As a small molecule with drug-like physicochemical properties and ease of synthesis, it has flexible routes and schedules of administration. Although designed for use as a combination agent, CX-4945 represents the first CK2 inhibitor to enter the clinic, therefore the Phase I setting was used to de-risk this new class of agent. A successful Phase I clinical trial demonstrated that it has favorable safety, pharmacokinetic and pharmacodynamic characteristics. CX-4945 hits the CK2 target and it modulated the expected pathways without displaying toxicity. The monitoring of circulating tumor cells demonstrated the ability of CX-4945 to kill tumor cells in patients which supports the observation that CX-4945 achieved clinical benefit as a single agent CK2 inhibitor, demonstrating stable disease and extended duration on treatment in a several patients. These findings positions CX-4945 for success in upcoming Phase II trials. The Phase II randomized drug combination trials are supported by compelling mechanistic rationales which guide selection of indications and shape trial designs. As such Cylene is initiating a trial with gemcitabine/carboplatin in ovarian cancer (DNA damage repair) and also initiating a trial with erlotinib in NSCLC (EGFR pathway).
Second Generation CK2 Inhibitors
Cylene has built upon the success of its CK2 inhibitor program and continued to deliver compounds with the characteristics required for clinically useful combination agents. This has generated compounds from several distinct chemical classes that potently and selectively inhibit CK2 in vitro and in vivo. The most promising of these are in preclinical evaluation.
