Cequent Pharmaceuticals, apioneer in the development of novel products to deliver RNAi-based treatmentsto prevent and treat human disease, has announced that it has filed its firstIND (investigational new drug) application with the U.S. Food and DrugAdministration (FDA). CEQ508, an orally administered tkRNAi drug candidate,targets beta-catenin, a key oncogene implicated in the formation of colonicpolyps and in the progression of polyps to colorectal cancer. Cequent expectsto begin the Phase I clinical trial in the FAP (familial adenomatouspolyposis) patient population during the first quarter of 2010 at the FredHutchinson Cancer Research Center, in Seattle, Washington, part of the FredHutchinson/University of Washington Cancer Consortium. "A first IND filing is obviously a momentous event for a young companylike Cequent, and this is also a critical milestone in the development of RNAitherapeutics in general, as our proposed Phase I trial will be the first testof an orally administered RNA interference drug in humans," said Cequent ChiefExecutive Officer Peter Parker. "In 2006, when RNAi was the subject of theNobel Prize in Medicine, it was hailed as 'a revolution in biology' - RNAi'sdiscovery created the opportunity to address targets that were previouslydifficult to treat by effectively deactivating the specific gene or genesimplicated in the progression of a disease by "interfering" with messengerRNA. However, success in developing RNAi therapies has been elusive to datebecause of delivery issues - how do you transport and deposit the moleculestriggering RNAi into the target cells and diseased tissues. We believe thatour orally administered tkRNAi technology has shown great potential in solvingthat significant problem." This Phase I clinical trial, as proposed to the FDA, would be conducted todetermine safety and tolerability of CEQ508 at escalating doses in a total of18 adult FAP patients. A key readout and secondary objective of the proposedtrial includes analysis of biomarker (beta-catenin) expression changes in thegastrointestinal tract of patients determined from biopsy samples taken priorto taking the drug, and following a daily, 28-day dosing regimen. Theprincipal investigator (PI) of this clinical trial will be Gideon Steinbach,M.D., Ph.D., associate professor of medicine at the University of Washingtonand the PI of a number of earlier FAP studies. The Cancer Consortium maintainsa registry of FAP patients and is also one of 40 National CancerInstitute-designated comprehensive cancer centers nationwide.In preclinical testing with non-human primates, tkRNAi therapeuticcandidates have demonstrated potent silencing of the beta-catenin, a proteinknown to accumulate and lead to the proliferation of polyps in affectedpatients. During preclinical testing, CEQ508 demonstrated an encouragingsafety profile when administered as a daily oral therapeutic. FAP is a rare inherited gastrointestinal disease that causes hundreds tothousands of precancerous polyps to form in the colon. Approximately 35,000people in the U.S. carry the genetic mutation inherent to the disease. Today,without prophylactic removal of the colon, people with FAP almost inevitablydevelop cancer, and there is no generally accepted pharmacological treatmentavailable. FAP has been designated as an orphan disease under the U.S. OrphanDrug Act, which provides various incentives for sponsors to encouragedevelopment of products for rare diseases. Phase I studies of noveltherapeutics for such rare, underserved diseases are often allowed to enrollpatients as opposed to healthy volunteers, potentially accelerating thetimeline to develop approved products. Commenting on Cequent's progression as a company, Mr. Parker said, "Wealso continue to make important progress with our tkRNAi inflammatory boweldisease (IBD) program, for which this CEQ508 trial serves as a regulatory andsafety pathbreaker. Cequent is moving ahead with preclinical development oftkRNAi products targeting immunological genes implicated in the pathology ofIBD." Mr. Parker continued, "We have now entered a new phase in the company'slifecycle; we have transitioned away from research to focus on our clinicalprograms, much of which we will pursue with contract resources. As such, wehave promoted Alison Silva to the new position of vice president of drugdevelopment, overseeing all clinical development and regulatory affairs forthe company. Co-inventor of the tkRNAi technology, Johannes Fruehauf, M.D.,will support the upcoming clinical trial through a consultancy arrangement asvice president of medical affairs."