Cequent Pharmaceuticals, a pioneer in the development of novel products to deliver RNAi-based treatments to prevent and treat human disease, has initiated a long-term (26-week) toxicology study of CEQ508 – the company’s lead drug candidate based on its proprietary tkRNAi technology. This study is designed to enable a phase-II clinical trial slated for 2011. 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. As an addition to this study, Cequent has begun dosing with the therapeutic candidate optioned by Novartis to enable an upcoming IND application in inflammatory bowel disease (IBD).
“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. “First, it serves as a Phase II-enabling toxicity study for our FAP drug, CEQ508. The FDA accepted our IND application for CEQ508 in December, and we expect to initiate our first-in-man Phase I trial in FAP (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. We designed the study to evaluate the safety profile of both drug candidates, as well as to demonstrate efficacy of our tkRNAi technology to silence the
intended gene target.”
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. The 26-week study announced today will evaluate standard toxicology parameters including clinical observations, body weight, ECGs, blood pressure, food consumption, rectal temperature, ophthalmology, urinalysis, hematology, coagulation, and serum chemistry. In addition, there will be monthly endoscopies with biopsies to examine beta-catenin levels in the gut mucosa every 28 to 30 days including at baseline (before dosing) and upon recovery (after seven days of no dosing), and fecal sample collection to analyze shedding and clearance of the bacteria through the gastrointestinal tract.