RNAi drug to treat colon polyps CEQ508 in safety studies: Sequent

CEQ508, a once-daily oral therapy to treat colon polyps, is currently in clinical studies to evaluate its safety in humans, according to Cequent Pharmaceuticals.

CEQ508 targets beta-catenin, a key oncogene implicated in the formation of colonic polyps and in the progression of polyps to colorectal cancer.

The non-human primate (NHP) study will evaluate safety and gene knock-down with once-daily oral administration of CEQ508.

Cequent has begun dosing with the therapeutic candidate optioned by Novartis to enable an upcoming IND application in inflammatory bowel disease (IBD).

The long-term (26-week) toxicology study is designed to enable a Phase II clinical trial slated for 2011.

“This study is another important milestone in the development of tkRNAi-based therapeutics – an entirely new class of drugs – and it accomplishes two significant objectives at once,” said Cequent chief executive officer Peter Parker.

US FDA accepted Cequent IND application for CEQ508 in December, and the company expects to initiate first-in-man Phase I trial in familial adenomatous polyposis patients for CEQ508 this quarter.

Second, it will provide important data on the Novartis IBD target in support of an FDA IND application, which we expect to file early next year. We believe the IBD target could be useful for patients suffering from ulcerative colitis.

In previous trials 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.

Cequent will present additional details about Cequent’s clinical development program on Tuesday, April 20, 2010, at the American Association for Cancer Research (AACR) annual meeting in Washington, D.C., which will be held at the Walter E. Washington Convention Center.

What is familial adenomatous polyposis (FAP)?

Familial adenomatous polyposis  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 U.S. carry the genetic mutation inherent to the disease, and the clinical researchers studying this disease have identified virtually all FAP patients.

Without prophylactic removal of the colon, people with familial adenomatous polyposis 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.

Phase I studies of novel therapeutics for such rare, underserved diseases are often allowed to enroll patients as opposed to healthy volunteers, potentially accelerating the timeline to develop approved products.

An early-stage biopharmaceutical company, Cequent is pioneering the development of novel therapeutics to treat disorders including inflammatory disease to cancer, based  – based on the company’s proprietary technology, TransKingdom RNA interference (tkRNAi).

Cequent’s first products, now entering clinical development, are orally administered drug candidates targeting colon-cancer prevention and inflammatory bowel disease.

The company designed its powerful tkRNAi technology as a therapeutic to deactivate specific disease-causing genes safely and effectively, using non-pathogenic bacteria as an engine to produce and deliver RNAi directly into cells.

It is based on ground-breaking scientific research originating at the Institut Pasteur (Paris, France) and at the Beth Israel Deaconess Medical Center/Harvard Medical School. A privately held company based in Cambridge, Massachusetts, Cequent was established in 2006.