Cequent Files IND For CEQ508 With FDA

Cequent Pharmaceuticals (Cequent) has filed an investigational new drug (IND) application with the FDA. CEQ508, an orally administered tkRNAi drug candidate, targets beta-catenin, a key oncogene implicated in the formation of colonic polyps and in the progression of polyps to colorectal cancer.

Cequent expects to begin the phase I clinical trial in the FAP (familial adenomatous polyposis) patient population 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 company said that the clinical trial, as proposed to the FDA, would be conducted to determine safety and tolerability of CEQ508 at escalating doses in a total of 18 adult FAP patients.

A key readout and secondary objective of the proposed trial includes analysis of biomarker (beta-catenin) expression changes in the gastrointestinal tract of patients determined from biopsy samples taken prior to taking the drug, and following a daily, 28-day dosing regimen.

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

Peter Parker, CEO of Cequent, said: “A first IND filing is obviously a momentous event for a young company like Cequent, and this is also a critical milestone in the development of RNAi therapeutics in general, as our proposed Phase I trial will be the first test of an orally administered RNA interference drug in humans.”

“We believe that our orally administered tkRNAi technology has shown great potential in solving that significant problem. We also continue to make important progress with our tkRNAi inflammatory bowel disease (IBD) program, for which this CEQ508 trial serves as a regulatory and safety pathbreaker. Cequent is moving ahead with preclinical development of tkRNAi products targeting immunological genes implicated in the pathology of IBD.”

“We have now entered a new phase in the company’s lifecycle; we have transitioned away from research to focus on our clinical programs, much of which we will pursue with contract resources. As such, we have promoted Alison Silva to the new position of vice president of drug development, overseeing all clinical development and regulatory affairs for the company. Co-inventor of the tkRNAi technology, Johannes Fruehauf, will support the upcoming clinical trial through a consultancy arrangement as vice president of medical affairs,” he added.”