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As it finalizes details for a new Phase III trial with Huntington's disease drug Miraxion, Amarin Corp. plc is bolstering its neuroscience pipeline, adding a messenger RNA (mRNA) platform technology and a midstage compound for myasthenia gravis through its acquisition of privately held Israel biotech Ester Neurosciences Ltd.

The deal calls for Amarin to pay $15 million up front, which includes $5 million in cash - expected to come from $8.1 million in proceeds from public offerings to close this week - and $10 million in stock, with up to $17 million in milestone payments upon successful clinical development of EN101, an acetylcholinesterase inhibitor currently being tested in a Phase IIa trial in myasthenia gravis.

That compound was the first to emerge from Ester's mRNA platform targeting the cholinergic pathway.

"Oftentimes, you see a platform technology with little or no clinical data," said Rick Stewart, CEO of London-based Amarin, as he explained the company's interest in Ester. "This was one of the few opportunities when we were able to see [the technology] validated by compelling clinical data."

Phase Ib data and interim results from the ongoing Phase IIa trial have shown EN101 "to be far superior to the current standard of care," Stewart told BioWorld Today.

Interim Phase IIa analysis showed that all three doses of EN101, given orally once a day, demonstrated statistically significant improvement over baseline, compared to Mestinon (pyridostigmine bromide, Valeant Pharmaceuticals) in patients with myasthenia gravis, a chronic autoimmune neuromuscular disease characterized by progressive muscle weakness.

EN101 has been granted orphan drug status in that indication.

Amarin plans to continue the Phase IIa study, and "expects to complete that around the third quarter of 2008," he said. The company anticipates wrapping up the Phase II program, along with chemistry and manufacturing activities and some additional preclinical work, in late 2009 or early 2010, after which, pending positive results, it will advance the product into Phase III.

If EN101 or any other product from Ester's technology makes it to market, Amarin has agreed to pay a 7 percent royalty to Yissum, the technology transfer arm of Hebrew University, and if Amarin partners AN101 for indications other than myasthenia gravis, it will pay Ester shareholders 10 percent of any license fees, milestones and royalties from the deal.

In preclinical testing, EN101 also has shown activity in other peripheral nervous system disorders, such as amyotrophic lateral sclerosis.

And the potential of Ester's mRNA platform extends even further, Stewart said, with early data exhibiting anti-inflammatory effects, as well as activity on the Toll-like receptor 9 signaling pathway.

Overall, he added, the acquisition will fit nicely with Amarin's pipeline, which leads with Miraxion for Huntington's disease, which, though it missed its primary and secondary endpoints in two pivotal trials earlier this year, is getting another chance.

"More sophisticated analysis" of the Phase III data showed statistical significance of Miraxion over placebo, Stewart said, and the "FDA indicated to us that, if we conduct another Phase III study that has robust results, they would accept" results from the previous studies as supportive data. (See BioWorld Today, April 25, 2007.)

Amarin is "still in the process of designing that trial," he said, adding that the new Phase III likely will start sometime next year.

Miraxion, a semi-synthetic, highly purified eicosapentaenoic acid (EPA), is designed to work by stabilizing cell membranes and the mitochondrial integrity of neurons.

Elsewhere in its pipeline, Amarin has an EPA product heading to Phase II in age-associated memory impairment, and a sublingual formulation of the Parkinson's disease drug apomorphine getting ready to start its third and final pharmacokinetic study. Both those trials are expected to begin early next year.

According to Stewart, Amarin's "whole commercial strategy focuses on diseases that we can handle with a small sales force," and the firm plans to build that sales force in the U.S., while seeking partners for marketing its neuroscience products in Europe.

In October, the company launched a cardiovascular program using its EPA platform, and last week started its first Phase I trial of ultra-pure ethyl EPA in combination with niacin in niacin-induced flushing.

The entire cardiovascular platform will be partnered worldwide, Stewart said.

Amarin also has another program in the works involving its targeted lipid transport technology to improve existing drugs.

The company also reported this week that it is raising $8.1 million in two public offerings to support the Ester acquisition. In the first offering, Amarin is getting $5.4 million from investors in exchange for 16.3 million American depositary shares priced at 33 cents each. Investors also will get five-year warrants to purchase 8.1 million ADSs at 48 cents apiece.

The second offering is expected to bring the company $2.7 million in aggregate principal amount of three-year convertible notes.

Company directors and officers committed $1.7 million of the total funding.

Rodman & Renshaw LLC served as placement agent.

Amarin, which posted a net loss of $5.9 million, or 6 cents per share, for the third quarter, had $20.7 million in cash, as of Sept. 30.

Stewart said the firm has "sufficient cash through the end of 2008," not including any potential cash from partnerships.

Amarin, which had 97.8 million shares outstanding as of Sept. 30, also said it plans to ask shareholders to approve a 1-for-10 reverse stock split at the general meeting in January, which will help the company regain compliance with Nasdaq listing requirements.

The firm received a Nasdaq deficiency letter in June stating that its stock was below the minimum bid requirement for continued listing.

Amarin's stock (NASDAQ:AMRN) closed at 33 cents Wednesday, down 3 cents.