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FDA grants Cequent investigational new drug for CEQ508 and clears way for first ever clinical trial of orally delivered RNAi therapeutic

Cequent Pharmaceuticals, a biopharmaceutical company that develops products to deliver RNAi-based treatments for the prevention and treatment of human disease, announced recently that the FDA Center for Biologics Evaluation and Research has approved Cequent’s first investigational new drug (IND) application.

This enables Cequent to initiate the first ever trial of an orally administered RNA interference (RNAi) drug in humans: CEQ508, the company’s lead drug candidate. CEQ508 targets beta-catenin, a key oncogene implicated in the formation of colonic polyps and in the progression of polyps to colorectal cancer.

‘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.

The FDA approved Cequent’s proposed clinical protocol for the Phase I clinical trial. 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, after 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 before taking the drug and at the end of the dosing period.

With the FDA’s approval of the clinical trial protocol, Cequent 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.

The Phase I familial adenomatous polyposis (FAP) trial will serve as a proof of concept for Cequent’s TransKingdom RNA interference (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.’

FAP is a rare, inherited gastrointestinal disease that causes hundreds to thousands of precancerous polyps to form in the colon of an affected individual. Approximately 35,000 people in the USA carry the genetic mutation inherent to the disease, and the clinical researchers studying this disease have identified virtually all FAP patients. Today, without prophylactic removal of the colon, people with FAP almost inevitably develop cancer, and there is no generally accepted pharmacological treatment available. FAP has been designated as an orphan disease under the U.S. Orphan Drug Act, which provides various incentives for sponsors to encourage development of products for rare diseases.

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. In addition, CEQ508 exhibited an encouraging safety profile when administered as a daily oral therapeutic.

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