Last updated on April 17, 2014 at 17:30 EDT

Cylene Advances Breakthrough p53 Activator Toward the Clinic

October 13, 2011

SAN DIEGO, Oct. 13, 2011 /PRNewswire/ — Cylene Pharmaceuticals, Inc. has advanced its targeted, non-genotoxic, activator of p53 for the treatment of leukemias, lymphomas and multiple myeloma through formal preclinical development, the Company announced today. The small molecule, CX-5461, avoids the direct DNA damaging side-effects typically seen with current p53 activating drugs by selectively inhibiting the newly-validated RNA Polymerase I (Pol I) cancer target. Upon activation the p53 protein functions as a tumor suppressor by causing cancerous cells to self-destruct. By targeting Pol I to activate p53 in blood cancers, Cylene’s first-in-class agent safely triggers the body’s natural cancer fighting capability to selectively kill tumor cells.

The US Patent Office recently awarded patent coverage for CX-5461 to Cylene, thereby expanding the Company’s extensive Pol I intellectual property portfolio. Cylene’s unique mechanistic knowledge and chemistry expertise enabled creation of molecules that act through direct inhibition of Pol I, leading to disruption of the Mdm2-p53 interaction and activating p53 to kill cancer cells. The appealing mechanism of action, highly favorable preclinical profile, robust in vivo efficacy in multiple models and bioavailability in multiple species, underpin Cylene’s decision to develop CX-5461 as a clinical candidate.

“CX-5461 looks like a promising agent for patients with leukemia, lymphoma and some types of solid tumors. Selective and potent activation of p53 by agents that do not damage DNA is a unique approach,” stated Daniel D. Von Hoff, M.D., Cylene’s Senior Vice President, Medical Affairs. “The successful targeting of Pol I provides the ideal non-genotoxic path for p53 activation and has the potential to deliver a new class of powerful anticancer therapies to our patients.”

“Advancing CX-5461 toward the clinic is a real testament to our ability to capitalize on new targets and we take great pride in the fact that Cylene is leading the industry in exploiting p53 through this novel mechanism,” commented William G. Rice, PhD, President and CEO of Cylene Pharmaceuticals. “We expect this molecule to satisfy a substantial need in the battle against leukemias, lymphoma and myelomas.”

About Pol I and CX-5461

CX-5461 represents an innovative targeted agent with numerous differentiating features when compared to current options for treatment of hematologic cancers. CX-5461 is a first-in-class small molecule inhibitor of RNA polymerase I (Pol I) that triggers the nucleolar stress surveillance pathways to activate p53, without causing direct DNA damage. The tumor suppressor protein p53, known as “the guardian of the genome,” orchestrates cellular responses to diverse stress factors. Activation of this protein can lead to cell cycle arrest or cell death and it is pivotal in determining whether cancer cells proliferate or die. Activation of p53 has long been an attractive approach to treating cancers, yet it has not been successfully exploited in the clinic. In particular, activation of p53 is relevant for hematologic malignancies, in which the vast majority of cancers have wild-type p53 status. CX-5461 inhibits upregulated Pol I transcription in cancer cells, causing the release of ribosomal proteins (RP) from the nucleolus. These RP then bind to Mdm2, liberating p53 from the Mdm2-p53 complex to induce apoptosis in cancer cells. Inhibition of the newly validated Pol I target by CX-5461 provides an innovative path to activate p53 and treat hematologic malignancies.

About Cylene Pharmaceuticals

Cylene Pharmaceuticals is a clinical stage private company developing small molecule drugs against newly validated cancer targets. Cylene’s leadership in exploiting CK2 pathways enables rational drug combinations for improved treatment outcomes against many cancer indications. The Company’s Pol I program provides a non-genotoxic mechanism for activating p53 to kill cancer cells. Cylene’s pioneering approaches deliver first in kind cancer agents that enable pharmaceutical companies to expand their portfolios and extend the efficacy, lifecycle and reach of current cancer therapeutics. For more information on Cylene and its programs, please visit www.cylenepharma.com.

SOURCE Cylene Pharmaceuticals, Inc.

Source: PR Newswire