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Santaris Plans IND for First miRNA Drug By Year End, Puts IPO Plans on Hold

Santaris plans to file an investigational new drug application for a microRNA antagonist for metabolic diseases before the end of the year, a move that would put the Danish company on track to become the first to test an miRNA drug in humans, a company official said last week.
Meantime, another official has said that the company has put on hold its plan to become publicly traded.
Speaking to investors at the Acumen Biofin Rodman & Renshaw Healthcare Conference in New York last week, Santaris Vice President and CFO Henrik Stage said that the company is currently conducting rodent and primate toxicology studies of its miRNA-targeting candidate, called SPC3649, as GMP synthesis of clinical materials ramps up.
With this work underway, “we would like to file the IND … in Q4 2007,” he said during his webcast presentation.
Stage also said that Santaris has almost closed a €20 million ($29.1 million) Series C round of financing, which is expected to enable the company to fund its operations through the end of 2009.
Earlier in the year, Santaris President and CEO Keith McCullagh said during a corporate presentation that the firm had been considering an initial public offering to raise the capital needed to advance its pipeline (see RNAi News, 5/24/2007).
However, with the Series C round nearing its close, Santaris has put the possibility of going public on the backburner.
“It is certainly something the board is looking at … but …we’re not planning on doing an IPO in the next three to six months,” McCullagh told RNAi News this week. “Of course, I can’t comment on [what may happen] after that.”
What is known is that over the next couple of quarters Santaris aims to build up its presence in the US by establishing a subsidiary in the country, he added.
“We have a number of collaborators in the US … and we are evaluating at the moment where we might establish our research center in the USA,” McCullagh noted. “We hope to complete [this evaluation] by the end of the year and then in the first quarter of next year … set up a US subsidiary.”
miRNA Frontrunner
In mid-2006, Santaris formed a collaboration with the University of Copenhagen to create miRNA-targeting drugs with the support of a €1.3 million grant from the Danish government's Advanced Technology Foundation (see RNAi News, 5/4/2006).
At the time, Santaris said that the collaboration could result in a clinical candidate by the end of 2007. Based on comments Stage made at the Acumen Biofin conference, the company isn’t too far off that timeline.

“We’re not planning on doing an IPO in the next three to six months. Of course, I can’t comment on [what may happen] after that.”

But while a major focus of the consortium is oncology, the miRNA-targeting cancer drugs in Santaris’ miRNA pipeline are still in the discovery phase. As such, SPC3649 will likely be the first miRNA antagonist to enter the clinic.
Like Santaris’ other miRNA antagonists, the drug is a locked nucleic acid, which is essentially a nucleic acid analog in which the ribose ring is locked by a methylene bridge connecting the 2'-O atom with the 4'-O atom — features designed to increase the molecule’s affinity and stability. Santaris holds the exclusive global rights to LNAs for therapeutic applications.
SPC3649 targets miR-122, the most abundantly expressed miRNA in the liver and one that appears to play a role in cholesterol regulation and lipid metabolism. Various other companies are developing miRNA antagonists against miR-122 including Regulus Therapeutics, a joint venture between Alnylam Pharmaceuticals and Isis Pharmaceuticals (see RNAi News, 9/13/2007).
Although Santaris sees possible utility for a miR-122 antagonist in various metabolic disorders including hyperlipidemia and obesity, its initial interest in SPC3649 is as a treatment for hepatitis C.
“The most interesting application, to our mind, is [hepatitis] C … partly because [miR-122’s] role in controlling lipid metabolism in the liver is still somewhat unclear and we need to do quite a lot of further work before we can position it as a … treatment of hyperlipidemia,” McCullagh explained.
A final decision on which indication Santaris will first pursue with SPC3649 will be made after phase I testing, where the drug’s effect on triglyceride and fatty acid metabolism can be examined, he said. But right now, HCV is the frontrunner.
“Not to say it won’t have applications elsewhere, but [hepatitis C] is our main commercial goal at the moment,” he said.
At the conference, Stage said that non-human primate studies have shown that SPC3649 administered via IV bolus can trigger “a very dramatic reduction in total plasma cholesterol” at doses ranging from 3 mg/kg to 10 mg/kg.
Given to the animals on days 1, 3, and 5, the drug also maintains its dose-dependent, cholesterol-lowering effect out to 90 days, he said.
As for SPC3649’s effect on hepatitis C, Stage said that in vitro experiments have shown that the drug can inhibit viral replication in human hepatocellular cells at low doses, Stage noted.
McCullagh said that the phase I trial of SPC3649 in healthy adult volunteers is expected to officially begin in the first half of 2008, probably at sites within Europe.

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