Marina Biotech, Inc. a leading RNAi-based drug discovery and development company, announced the initiation of patient dosing in the Dose Escalation phase of its START-FAP (Safety and Tolerability of An RNAi Therapeutic in Familial Adenomatous Polyposis) clinical trial with CEQ508.

Marina Biotech's phase I b/II a trial is an open-label, escalating-dose study of single daily doses of CEQ508 and will be conducted as a single centre study in Boston, Massachusetts. The first cohort comprised of three patients will be administered the starting dose of 1x10(8) colony forming units (cfu)/day.

The study is primarily designed to evaluate the safety and tolerability of CEQ508 in patients with Familial Adenomatous Polyposis (FAP) after 28 days of daily, oral dosing. The trial is also intended to provide data on beta-catenin biomarker changes pre- and post-treatment and pharmacokinetic data related to the gastrointestinal coverage of CEQ508. The Dose Escalation phase consists of 12 patients in four dose escalating cohorts; two patients in the first dosing group have been enrolled.

“We're very pleased to be able to announce the initiation of patient dosing in our START-FAP trial,” stated J Michael French, president and CEO at Marina Biotech. “The trial will allow us to establish the most appropriate once-daily dose for further clinical development, and will augment our existing safety database for CEQ508. In combination with the recently completed long-term non-human primate safety study and the orphan drug designation granted late last year, we remain on a rapid clinical development timeline for commercialization of CEQ508. We believe CEQ508 has the potential to be a safe and efficacious therapeutic for a patient population with no currently approved pharmaceutical alternative.”

CEQ508 is the first drug candidate in a novel class of therapeutic agents utilizing the transkingdom RNA interference (tkRNAi) platform. CEQ508 comprises attenuated bacteria that are engineered to enter into dysplastic tissue and release a payload of short-hairpin RNA (shRNA), a mediator in the RNAi pathway. The shRNA targets the mRNA of beta-catenin, which is known to be dysregulated in classical FAP.

CEQ508 is being developed as an orally administered treatment to reduce the levels of beta-catenin protein in the epithelial cells of the small and large intestine. Upon enrollment, patients will be placed in one of four dose-escalating cohorts. Following completion of the dose escalation phase, the trial plan calls for a stable-dose phase in which additional patients will receive the highest safe dose. CEQ508 will be administered daily in an oral suspension for 28 consecutive days.

CEQ508 is being developed for the treatment of Familial Adenomatous Polyposis (FAP), a hereditary condition that occurs in approximately 1:10,000 persons worldwide. FAP is caused by mutations in the Adenomatous Polyposis Coli (APC) gene. As a result of these mutations, epithelial cells lining the intestinal tract have increased levels of the protein beta-catenin, which in turn, results in uncontrolled cell growth. Proliferation of the epithelial cells results in the formation of numerous (hundreds to thousands) non-cancerous growths (polyps) throughout the large intestine. By age 35, 95% of individuals with FAP have developed polyps and most will experience adverse effects including increased risk of bleeding and the potential for anaemia.

In more severe cases, obstruction of the intestines, abdominal pain, and severe bouts of diarrhoea or constipation can occur. FAP patients are also at an increased risk of various cancers, the most concerning of which is a nearly 100% occurrence of colon cancer if measures are not taken to prevent the formation of polyps. For many patients, complete colectomy (surgical removal of the entire large intestine), usually performed in the late teenage years or early twenties, is the only viable option for treatment. However, surgical intervention is not curative as the risk of polyps forming in the remaining portions of the intestinal tract and in the small intestine continues after colectomy.

Marina Biotech is a biotechnology company, focused on the development and commercialization of RNA interference- (RNAi) and RNA-based therapeutics. It currently includes a clinical program in Familial Adenomatous Polyposis (a precancerous syndrome) and two preclinical programmes -- in hepatocellular carcinoma and bladder cancer.