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Marina Pipeline on Track with FAP Trial in 2010, But Could Miss Partnership Guidance

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By Doug Macron

Officials from Marina Biotech last week reported that the company remains on track to begin the first part of a phase Ib/IIa trial of its oral familial adenomatous polyposis treatment CEQ508 before the year is out, and that its program in bladder cancer is expected to yield an investigational new drug application in 2011.

And while Marina is "committed" to meeting its previously announced guidance of forging at least two pharmaceutical industry partnerships in 2010, the company's vice president of corporate development, June Ameen, indicated that it may miss this goal if the terms of the deals aren't right.

The comments were made during a conference call held to discuss Marina's third-quarter financial results.

CEQ508 is based on Cequent Pharmaceuticals' so-called transkingdom RNAi technology, which uses orally delivered attenuated Escherichia coli to transcribe therapeutic shRNAs. The drug is designed to inhibit the oncogene beta-catenin as a way to inhibit the formation of the colorectal polyps that characterize FAP, and potentially slow the progression to malignancy of existing ones.

Marina acquired the drug when it bought Cequent earlier this year (GSN 4/1/2010).

According to Marina CSO Barry Polisky, CEQ508 is slated to enter the clinic "in the coming weeks" in the first portion of a planned phase Ib/IIa trial that will be conducted at Massachusetts General Hospital.

"The first phase is a dose-escalating study during which 12 patients with FAP will receive a single dose of CEQ508 daily for 28 consecutive days," he said during last week's call. "Doses will escalate through four dosing levels during the course of this phase of the study."

Once this portion of the study is completed, Marina will begin a "stable-dose phase in which six additional patients will receive the highest safe dose," he said. "Patient enrollment will take place up to 30 days prior to patient dosing to allow for the scheduling of baseline procedures including upper and lower endoscopies."

The primary endpoint of the trial is safety and tolerability, but it will also evaluate changes in beta-catenin levels. To do so, biopsies from patients' large and small intestines, taken before and after treatment, will be analyzed and compared, Polisky explained.

Marina will also examine changes in expression of genes in the Myc and K-ras pathways, Alison Silva, Marina's vice president of drug development, noted during the call.

Polisky said that Marina anticipates starting a phase IIb study of CEQ508 in early 2012, and has been conducting extended non-human primate toxicology work in anticipation of this forthcoming trial.

Late last month, the company released six-month data from these toxicology experiments showing the drug to be safe.

Currently, "we are approximately 210 days into this study" with the animals receiving the highest dose expected to be tested in humans, Polisky said. "We've seen no test article-related toxicity in the animals as measured by clinical observations and pathology."

Marina President and CEO Michael French said in a statement that, based on the progress thus far, Marina is still anticipating that it could move CEQ508 onto the market as early as 2014.

In April, he said that the company could also be in a position to market the drug on its own, given the small number of FAP patients, CEQ508's orphan drug designation in the US, and the fact that a COX-2 inhibitor was previously approved to treat FAP only on phase II data, although that drug was later pulled from the market due to toxicity concerns with all drugs in its class (GSN 4/8/2010).

Meanwhile, Marina continues to advance its preclinical non-muscle-invasive bladder cancer program — its flagship drug-development effort prior to the Cequent acquisition — which involves the local administration of the company's proprietary UsiRNA constructs in liposome nanoparticles. Based on continued safely and efficacy in animal models, the company expects to file an IND on a bladder cancer candidate next year.

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From a business standpoint, Marina is "working diligently to achieve our publicly stated objectives of closing two pharma transactions by the end of this year," Ameen said. "Although we are now in November, we do expect to achieve these … goals" as negotiations with potential partners continue.

But Marina, it seems, is not discounting the possibility that it could miss this goal as it competes with other companies in the RNAi space for industry alliances.

"We will continue to ensure that the deals we are putting together best maximize the long-term value of Marina Biotech," Ameen noted, cautioning that while "we are committed to delivering on our guidance … [we] won't enter into a deal simply to meet our end-of-the-year goals."

She said that Marina was unable to provide additional information on the partnership front.

The Third Quarter

For the three-month period ended Sept. 30, Marina's net loss climbed to $8.3 million, or $0.39 per share, from a year-ago loss of $7 million, or $0.69 per share.

Revenues in the quarter jumped to $1.1 million from $100,000, reflecting $800,000 in revenue related to the sale of an intranasal carbetocin program, a legacy asset from before the company's transition to a pure-play RNAi firm.

Research and development spending in the quarter surged to $7.5 million from $3.3 million, which included $3.8 million in patent license fees related to Marina's acquisition of Novosom's Smarticle delivery technology this summer (GSN 7/29/2010).

Third-quarter selling, general, and administrative costs, meantime, edged up to $7.9 million from $7.8 million.

At the end of the third quarter, Marina had cash and cash equivalents totaling $2.1 million. Earlier this month, the company grossed $3.3 million in a stock offering and secured roughly $733,000 in grants under the Internal Revenue Service-funded Qualifying Therapeutic Discovery Project program (GSN 11/4/2010).

With these added funds, Marina said it has the resources to fund its operations "into the first quarter of 2011."


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