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Startup Cequent Jumps Onto RNAi Drugs Field With $6M VC Funding and Novel Delivery Tech

The RNAi therapeutics field got a little bigger late last year with the establishment of Cequent Pharmaceuticals, a Cambridge, Mass.-based firm developing RNAi drugs incorporating a novel bacteria-based delivery technology.
Called transkingdom RNAi, Cequent’s technology involves engineering non-pathogenic bacteria to express shRNAs. It was developed by company founder and director Chiang Li at Beth Israel Deaconess Medical Center.
Having closed a $6 million financing round in November, Cequent is now aiming to prepare the technology for clinical testing this year and file its first investigational new drug application in familial adenomatous polyposis by the second quarter of 2008, according to Cequent President and CEO Peter Parker.
FAP is an inherited colorectal cancer syndrome characterized by the growth of polyps on the colon. According to the Stanford Comprehensive Cancer Center, the condition, which affects about one in 8,000 individuals, leads to colorectal cancer in nearly all cases in the absence of colectomy.
Though FAP is a relatively small indication, affecting an estimated 40,000 people in the US, Parker told RNAi News this week that it is a good starting point for Cequent to demonstrate the efficacy of its technology.
FAP “is a gastrointestinal disease that the original [scientific team led by Li] had worked on … so it is the furthest along,” Parker said. But beyond that there exists a “significant unmet medical need” for such a therapy. He added that the market potential for a treatment is not insignificant because FAP is a chronic condition.
Patients “would have to be treated for their whole life,” he said. While Cequent doesn’t anticipate its treatment, an oral drug targeting beta-catenin, would be “terribly expensive,” there is a “very big market when you start thinking about long-term care.”
Parker also noted that production of the bacteria used in the transkingdom RNAi technology is straightforward enough to allow the company to file a series of INDs very rapidly — as many as one a year.
As such, Cequent expects to file an IND on a second indication in the first half of 2009, he said.
On its website, the startup firm lists among its therapeutic focuses inflammatory bowel disease, which comprises Crohn’s disease, uIcerative colitis, as well as pouchitis and colon cancer. However, Parker said this is a reflection of Li’s work in the division of gastroenterology at Beth Israel, and the company is considering a range of possible disease areas to tackle.
“What we’re furthest along in next is IBD,” he said. “Having said that … we honestly don’t know what we’re going to bring to the clinic next.” In addition to GI disorders and viral infections, the company is considering solid tumors “in accessible body cavities, for instance the bladder.”
Parker noted that a decision is likely to be made on a second therapeutic program by March.
Expressive E. coli
In May last year, Li and colleagues published research in Nature Biotechnology demonstrating how non-pathogenic Escherichia coli could be made to express specific shRNAs. According to the paper, the researchers engineered the bacterium to transcribe shRNAs from “a plasmid containing the invasin gene Inv and the listeriolysin O gene HlyA, which encode two bacterial factors needed for successful transfer of the shRNAs into mammalian cells.”

Cequent’s technology was developed by company founder and director Chiang Li at Beth Israel Deaconess Medical Center and involves engineering non-pathogenic bacteria to express shRNAs.

When administered either orally or intravenously, E. coli encoding shRNA against the oncogene CTNNB1 triggered “significant gene silencing in the intestinal epithelium and in human colon cancer xenografts in mice.”
In light of these and other data, Cequent was able to secure three investors — Ampersand Ventures, New England Partners, and Pappas Ventures — each of which put up $2 million in November and committed to invest an additional $1 million apiece when Cequent files its first IND. Parker noted, however, that the company is also looking for other investors and anticipates pulling in as much as $5 million when it files the IND.
With that cash in hand, Cequent is now preparing to move into its new Kendall Square headquarters at the beginning of March. The firm is also on the lookout for a scientific team to round out is staff, which currently is limited to five employees — all on the general and administrative side.
According to its website, Cequent is looking for scientists with backgrounds in bacteriology, molecular biology, and inflammatory diseases. The company is also looking for a cancer biology investigator and a number of research associates.
Parker said that by the second quarter of this year, Cequent expects to have about 19 staffers and be in a position to conduct the preclinical research needed to meet its IND timeline, as well as to conduct all phase I work in FAP once the company has been given the go-ahead by US regulators.

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