Cequent Pharmaceuticals' IND application for CEQ508 approved for clinical trial

Cequent Pharmaceuticals, a pioneer in the development of novel products to deliver RNAi-based treatments to prevent and treat human disease, announced that the U.S. Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER) approved Cequent's first IND (investigational new drug) application yesterday. This action enables Cequent to initiate the first-ever trial of an orally administered RNA interference drug in humans: CEQ508 - the company's lead drug candidate based on its proprietary tkRNAi technology. CEQ508 targets beta-catenin, a key oncogene implicated in the formation of colonic polyps and in the progression of polyps to colorectal cancer.

The IND application acceptance is the second procedural hurdle that the young company has cleared in order to begin human clinical trials of CEQ508 in the FAP (familial adenomatous polyposis) patient population. The company noted that the 14 reviewing members of the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health (NIH) voted unanimously to endorse the proposed clinical protocol after conducting an in-depth review and public discussion of the proposed CEQ508 program on September 9, 2009.

"We submitted our IND application to the FDA on November 9, 2009. Having our first IND application accepted in the 30-day period is an extraordinary accomplishment for any company, particularly so for Cequent, given that we are working on an entirely new class of drugs," said Cequent Chief Executive Officer Peter Parker. "It speaks volumes to the quality of the submission, which comprised more than 4,000 pages. I'm so proud of our scientific team, who, in a short time, were successful in turning an intriguing RNAi research concept into a viable drug candidate ready to be tested in humans."

The FDA approved Cequent's proposed clinical protocol for the Phase I clinical trial, including the choice of the adult FAP patient population, selection of cohort size, the dosing regimen, and duration of treatment. The trial is designed to determine safety and tolerability of CEQ508, starting with a dose-escalation phase in which patients will be given one of four escalating concentrations of the drug, contingent upon safety monitoring. This initial part of the clinical trial is expected to take approximately six months. Next, following a safety review, the trial plan calls for a stable-dose phase in which additional patients will receive the highest safe dose. The FDA will permit daily dosing of 18 or more patients for 28 days. A key readout and secondary objective of the trial includes analysis of biomarker beta-catenin expression changes in the gastrointestinal tract of patients determined from biopsy samples obtained prior to taking the drug and at the end of the dosing period.

Cequent's Vice President of Drug Development, Alison Silva, commented, "I want to commend the reviewers at CBER who have been very responsive, providing critical feedback immediately following our submission and throughout the application process. They worked with us so that we could address their questions quickly and effectively to reach a successful conclusion by our action date."

With the FDA approval of Cequent's clinical-trial protocol now in hand, the company has begun working with the proposed clinical center to obtain the necessary institutional approvals. Cequent expects to begin the Phase I clinical trial during the first quarter of 2010 at the Fred Hutchinson Cancer Research Center in Seattle, Washington, part of the Fred Hutchinson/University of Washington Cancer Consortium. The Cancer Consortium maintains a registry of FAP patients and is also one of 40 National Cancer Institute-designated comprehensive cancer centers nationwide. Gideon Steinbach, M.D., Ph.D., is slated to be the principal investigator (PI) of the Cequent trial. Dr. Steinbach is associate professor of medicine at the University of Washington, and served as the PI of a previous celecoxib FAP Phase II trial that established a high standard for polyposis trials.

The upcoming Phase I FAP trial will serve as a proof of concept for Cequent's tkRNAi technology, according to Mr. Parker. "We believe our technology offers an elegant solution to the RNAi delivery problem that has stymied significant progress in the field to date. We modify live, nonpathogenic bacteria in a proprietary process to produce and deposit mediators of RNAi directly into the target cells. Follow-on drug candidates could potentially address dozens of different gene targets associated with more common and equally serious diseases. For example, we continue to make progress on our preclinical program for inflammatory bowel disease."

In preclinical testing with non-human primates, Cequent's tkRNAi therapeutic candidates have demonstrated potent silencing of beta-catenin, a protein known to accumulate and lead to the proliferation of polyps in affected patients, and CEQ508 exhibited an encouraging safety profile when administered as a daily oral therapeutic.