Amarin Corporation PLC (AMRN) 2010 Q4 法說會逐字稿

Greetings and welcome to the Amarin Corp. fourth-quarter and 2010 year-end results conference call. At this time all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. (Operator Instructions). As a reminder, this conference is being recorded.

It is now my pleasure to introduce your host, Steve Schultz, Senior Director of Investor Relations. Thank you, sir. You may begin.

Welcome and thank you for joining us today. Before we comment on our financial and operating results, I remind everyone that today's call will include statements that are not historical and may be characterized as forward-looking statements as defined by the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding the timing and results of our clinical trials; the timing of our planned announcement and publication of these results; our current expectations regarding regulatory filings and potential indication for our product candidate if approved; the potential market opportunity for our product candidates; our current expectations regarding potential strategic collaborations; and the adequacy of our financial resources.

These statements involve various risks and uncertainties that could cause actual results to differ materially from those expressed in such forward-looking statements. And these include the risks and uncertainties under the heading Risk Factors in our most recent annual report on Form 10-K and other periodic reports filed with the SEC, which reports are available on our website at www.AmarinCorp.com. They are also available on the SEC's website.

These forward-looking statements are only predictions. Actual results or plans may vary materially from those projected. The forward-looking statements we make on today's call are based on our beliefs and expectations as of today, March 17, 2011 only. We do not undertake any obligation to revise or update such forward-looking statements. Please note that an archive of this call will be posted to the Amarin website.

I will now turn the call over to Joseph Zakrzewski, Executive Chairman and Chief Executive Officer of Amarin.

Thank you, Steve, and welcome to everyone who is joining us today. During this call we will provide a brief review of our 2010 accomplishments, clinical and regulatory status, and financial results.

I am joined on today's call by John Thero, President; Paresh Soni, Senior VP and Head of Development; and Fred Ahlholm, Amarin's VP of Finance. We will be available after our prepared remarks for a quick Q&A session.

First, let me say that we are very proud of the tremendous progress Amarin made over the past year. A year ago we were in the earliest stages of introducing investors to the fact that Amarin had a new management team and had begun focusing exclusively on developing products for cardiovascular indications.

We now have the Phase 3 pivotal MARINE trial successfully completed and a second pivotal Phase 3 study, the ANCHOR trial, scheduled to report topline results in Q2 this year. One other point of emphasis is that all employees, officers and directors of Amarin and our CEO are currently blinded to any and all results of the ANCHOR trial. We will remain blinded to such results until shortly before those results are publicly announced.

MARINE achieved its primary endpoints as we have previously discussed and disclosed. In accordance with our SPA for this trial, these results form the basis of an NDA submission based on the MARINE results independent of ANCHOR trial results.

This is to say that we are not optimistic about the results of the ANCHOR trial. We are very optimistic about those results and as Paresh Soni will describe, we believe that we have good cause for such optimism. I do want to reiterate that MARINE trial efficacy results are independent of the ANCHOR trial efficacy results, such that regardless of the ANCHOR trial outcome we still intend to go after greater than a $1 billion opportunity based on the MARINE results, while also considering pursuing the larger cardiac protection indication and/or other indications of AMR101.

2010 was a full year of accomplishments for Amarin. Some recent accomplishments of note include a successful financing in January, netting the Company approximately $99 million in cash, which significantly strengthened our balance sheet, allowing us to move forward more aggressively with commercial preparations and evaluation of potential partnering opportunities.

We also completed recently the last patient visit for the ANCHOR Phase 3 trial, positioning us after data collection and analysis from the 80 or so sites to report topline results in the second quarter, another major achievement. Continued progress based on the MARINE trial results and preparation of our NDA submission, giving us confidence that the NDA will be submitted to the FDA in the third quarter of this year.

In addition, we appointed Paul Huff, a former colleague of mine from Reliant, as our Chief Commercial Officer to lead the commercial preparations for AMR101. His track record is incredible in the cardiovascular market and has launched a number of drugs in the marketplace, and we are delighted to have Paul with us. Finally, continued support of partner interest in AMR101 and Amarin.

Our priorities for 2011 include announcement of topline data for ANCHOR trial in the second quarter, presentation of the complete dataset from the MARINE and ANCHOR trials at appropriate scientific conferences and securing various publications of the data; filing the NDA as discussed above earlier; and building the team and a foundation for commercializing AMR101. Then last but not least, qualifying additional suppliers to establish greater supply diversification and capacity in preparation for the AMR101 launch.

In this conference call, Paresh Soni will discuss clinical and regulatory activities. John Thero will discuss other aspects of our operating progress, and Fred Ahlholm is here to discuss our financial results. In a future conference call, I will ask our recently appointed Chief Commercial Officer, Paul Huff, to describe his perspective on the opportunity and positioning of AMR101. In this call, I will ask John Thero to make a few comments on our activities.

Our MARINE trial results exceeded our expectations. Our ANCHOR trial for which we anticipate reporting topline results in Q2 is running ahead of our internal guidance reporting results in 2012. Based on our understanding of the profile of AMR101, we believe that AMR101 is well-differentiated from potential competitors, risk-mitigated for regulatory approval, and well-positioned to address the $1 billion market opportunity based on the MARINE results alone.

We are also increasingly looking at other potential uses of AMR101 including, but not limited to, combination therapy with statins and cardiac protection. When I think about the market opportunity for AMR101, I think about the market growth which occurred when statins entered the market. Prior statins treatment for cholesterol management had significant weaknesses. Statins provided an effective solution as evidenced by the annual statin revenues of greater than $30 billion today.

What statins did for cholesterol we hope AMR101 does for triglycerides. Existing therapies for triglyceride management all have significant side effects including, but not limited to, demonstrated increases in LDL-C or bad cholesterol.

Our MARINE trial was designed to evaluate the effectiveness of AMR101 in addressing patients in the market for which the prescription Omega-3 drug, Lovaza, is approved and on track to sell nearly $1 billion in the US alone, and approximately $1.5 billion worldwide in 2011. This is a drug that Paul Huff, our Chief Commercial Officer, and I helped launch.

We believe that AMR101 is significantly differentiated from Lovaza to address unmet market needs and also fenofibrates in many clinical scenarios. As importantly, though, than taking market share from Lovaza, will be our opportunity to significantly grow this market which today we believe is significantly underpenetrated.

Moreover with our ANCHOR trial, we seek to address a population in the US which is 10 times larger in number of potential patients then the number of patients we are seeking approval for from the MARINE studies, MARINE trial results.

More specifically, approximately 4 million people in the US alone are diagnosed with very high triglyceride levels over 500 milligrams per deciliter, the indication which the MARINE trial was designed to evaluate the effect of AMR101 treatment. For this population, we believe that AMR101 is well-positioned to be the best-in-class product.

Additionally, approximately 36 million people in the US have high triglyceride levels between 200 and 500 milligrams per deciliter, a population for which we believe that AMR101 is well-positioned to be first-in-class as there is no prescription Omega-3-based drug approved for this indication.

Clinical treatment guidelines recommend that patients with triglyceride levels at or above 200 mg per deciliter should be treated with a prescription triglyceride lowering therapy. We believe that AMR101 is positioned to significantly differentiate itself from other Omega-3-based products and from fibrates in several important ways.

The key differentiator is that in the MARINE study, AMR101 demonstrated reductions of triglycerides by amounts comparable to other therapies, but without an increase in LDL-C. This compared to existing therapies that have been shown to increase LDL-C by up to 50% in this population.

Based on the composition of AMR101 which has a single active moiety, we anticipated that AMR would result in less of an increase in LDL-C than these other therapies. However, it was a very positive surprise for us that the MARINE trial showed an absence of LDL-C increase in patients on AMR101 compared to placebo. The MARINE study is the largest study ever conducted in the greater than 500 mg per deciliter population.

Again, to repeat what we've spoken about before, other problems that have resulted from the MARINE trial include demonstration that AMR101 was efficacious in both 4 and 2-gram doses; total cholesterol at non-HDL-C reductions which were larger than expected and larger than those described in the labels of the drugs that we will likely compete; very encouraging results on anti-inflammatory biomarkers, which are increasingly becoming focused on by cardiovascular experts as important markers of cardiovascular risk; a robust safety profile which is equivalent to placebo; and an array of novel findings supporting patent applications for multiple claims seeking patent protection through 2030.

For a more detailed discussion of our clinic clinical results and progress, I now turn the call over to Paresh. Paresh?

Thank you, Joe. AMR101 is a prescription grade Omega-3 fatty acid comprising not less than 96% ultrapure eicosapentaenoic ethyl or ethyl- EPA, being developed and positioned as a best-in-class prescription medicine for treating patients with elevated triglyceride levels.

Elevated triglyceride levels are increasingly being recognized as a significant modifiable risk factor for cardiovascular disease, alongside LDL cholesterol. As Joe mentioned, we are increasingly evaluating additional potential indications for AMR101.

However, our primary focus is on the success of AMR101 in our current Phase 3 clinical program and upon completion and submission of an NDA, seeking approval based on our Phase 3 results in the MARINE trial. The MARINE study evaluated the safety and effectiveness of AMR101 in 229 patients with very high triglycerides, as defined as being over 500 milligrams per deciliter.

We believe this trial can support a label similar to the drug Lovaza or Omacor, which is also a prescription Omega-3 and is marketed by GSK in the US and Abbott in Europe. The MARINE study is the largest ever conducted in this population and the first study with Omega-3 fatty acids in the post-statin era.

In November 2010, we announced that the MARINE study met the primary endpoints with high significant reductions in triglycerides at both the 4-gram and 2-gram doses. In addition to achieving these endpoints, the results of the trial exceeded our expectations by demonstrating no statistically significant increase in LDL cholesterol at either dose, triglyceride lowering that was better in the predefined subset of patients on statin therapy, and by showing encouraging results regarding other prespecified biomarkers.

Additionally, AMR101 demonstrates a safety profile similar to placebo. The open-label 40-week extension period for the MARINE trial is ongoing. To date, we have noted nothing in the resulting extension period which offsets our reasons for encouragement from the pivotal phase of the MARINE trial.

In contrast to previous studies of Omega-3 fatty acids and fibrate treatments for patients with very high triglyceride levels, AMR101 is the first triglyceride-lowering therapy demonstrated to reduce triglycerides without significantly increasing LDL cholesterol levels.

We have been working with our advisers on selecting an appropriate venue for the broader presentation of our MARINE trial results, and we are also working with investigators on the MARINE trial on various publications of the results. We are considering various presentation venues, including venues in the second, third and fourth quarter of 2010.

While we have a preference of presenting sooner rather than later, we want to ensure that presentations are done appropriately to have the right physician audience and long-term effect. When we have selected a conference or presentation, we will publicly announce this.

The ANCHOR study is evaluating the safety and effectiveness of AMR101 in 702 patients with mixed dyslipidemia or multiple lipid disorders who have triglyceride levels of 200 to 500 milligrams per deciliter, and who are also on statin therapy.

In the US, no prescription Omega-3 product is approved for this patient population. This study will also evaluate whether AMR101 is devoid of LDL cholesterol elevating effects commonly seen in patients with mixed dyslipidemia on statin therapy who take a common prescription Omega-3 therapy.

The last patient visit was recently completed in this study. Now data needs to be collected, quality checked and analyzed. The duration of time required for this activity, all of which is done by our CRO before we see any data, can vary significantly based in many factors, including the number of sites and their ability to close out site-related activities in a timely manner.

As previously disclosed, we anticipate having topline results of the ANCHOR trial ready to report in the second quarter of this year. Once we have access to these results, we will review the results and publicly report these promptly.

The ANCHOR trial's primary endpoint is statistically significant reduction in triglycerides at 4-gram and 2-gram doses. The secondary endpoint is noninferiority regarding LDL cholesterol as compared to placebo. The trial evaluates results at 4 grams first, and if successful, evaluates results at 2 grams. Based on our review of the performance of EPA lowering triglycerides, we are optimistic that AMR101 will achieve the ANCHOR trial endpoint at 4 grams. If, in addition, AMR101 also achieves the trial endpoint at 2 grams, that would be a bonus.

The MARINE trial and the ANCHOR trial have each been conducted under separate special protocol assessment agreements or SPAs with the FDA. I have been asked many times do express why we are optimistic that AMR101 will succeed in the ANCHOR trial. While there can be no assurance of success, my optimism comes from looking at the results of multiple studies conducted by other Omega-3-based drugs. In particular, the clinical study results from the Nomura study, as published in 2009, was a study conducted using Epadel in Japan. Epadel, as you know, is comprised of the same active ingredient as AMR101. In the Nomura study conducted with 191 patients, there was an overall decrease in triglyceride levels of 29%, of which 14% was attributed to statin therapy and 15% was attributed to Epadel. There was no elevation in LDL cholesterol when EPA was added to statin therapy in this study.

If we reach triglyceride reduction at this level in the ANCHOR study, that would be very pleasing. Note that there is no numerical target level of triglyceride reduction in the ANCHOR trial. Rather, the endpoint for the ANCHOR trial is to show a significant reduction in the triglyceride levels of patients on statin plus AMR101 compared to patients on statin plus placebo.

While we need to be cautious in extrapolating MARINE trial results to the ANCHOR study because the trials are just different patient populations, regarding LTL cholesterol our confidence in ANCHOR's potential to demonstrate LDL cholesterol neutrality compared to placebo is supported by the lack of LDL-C increase in MARINE where only 25% of the patients were on statin therapy.

However, in ANCHOR, 100% of the patients are on statin therapy and baseline triglyceride levels are lower, both of which factors should support LDL cholesterol neutrality. Elevated triglycerides have become increasingly important as an independent risk factor for cardiovascular disease.

While statins form the backbone of lipid-lowering therapy, a high residual risk of cardiovascular events remains in these patients. We are excited with anticipation of the ANCHOR results and the potential for Amarin to become the leader in addressing that residual risk with AMR101.

With respect to NDA preparations based on our favorable MARINE trial results, our aim is to submit an NDA or new drug application with the FDA in the third quarter of 2011. We are also evaluating whether the efficacy portion of the submission should be made initially based on MARINE trial results with a separate filing for ANCHOR efficacy results, or whether ANCHOR efficacy results should be included in the initial NDA submission. We will be able to comment further on this after we see the ANCHOR results.

Again, it is important to note that the MARINE data alone is sufficient for filing an NDA for the very high triglyceride indication, that is levels above 500 milligrams per deciliter.

One of the factors influencing whether we submit ANCHOR efficacy results at the same time as MARINE results or separately is the FDA requirement that we conduct an outcome study to support the ANCHOR indication. There is no outcome study requirement with respect to the MARINE results.

We are in the process of seeking FDA feedback on the design of an outcome study, which could potentially reach cardiovascular prevention indication, which is of interest to us regardless of the ANCHOR results, due to the large potential size of such an indication.

We are also seeking to clarify the timing and the cost of the outcome study. It is important to note that the results of the outcome study are not needed in order to secure approval for the ANCHOR indication, but we do need to have this outcome study well underway.

I would like to hand the call over to John Thero now for his perspective on certain business matters.

Thank you, Paresh. I will briefly address three topics. One, commercial preparations; two, supply; and three, observations regarding some recent insider selling. With respect to commercial preparations, we see multiple paths to create value.

Following the success of our MARINE trial, we are accelerating the pace of commercial preparedness with a need to be able to commercialize AMR101 on our own. This is the piece of our destiny that we control and accordingly, we are taking many actions to prepare for the launch of AMR101.

In addition to the strategic hiring of Paul Huff as our Chief Commercial Officer, we have begun building a medical affairs team, commenced various additional market research studies, commenced salesforce mapping, plus a variety of other activities and actions.

In parallel with this, we continue discussions with a broad list of potential partners. As you might imagine, our drug is attracting significant attention from potential partners as a cardiovascular drug with a multibillion-dollar potential positioned to enter the market in a timeframe when many big pharma companies are anticipating product pipeline weaknesses.

While we are optimistic about the opportunities these discussions represent, there can be no assurance that these discussions will lead to acceptable terms. Depending upon the outcomes of these discussions, it is possible that AMR101 could become commercially launched by a third party with or without the assistance of Amarin. Regardless, Amarin is committed to and has begun taking the steps necessary to prepare for launching AMR101 on our own.

On the topic of supply, following our better-than-expected MARINE results, we have by necessity increased our efforts to expand our supply capacity to meet what we believe is a large opportunity -- or essentially, a larger opportunity for AMR101 than anticipated prior to the MARINE results.

Similarly, suppliers with which we are working, they recognize this opportunity. And following the MARINE results, they too have demonstrated increased focus and interest on supply expansion. As you know, our current Japan-based supplier is working to increase supply. We are very pleased to be informed that this supplier was not directly affected by the recent earthquake and tsunami in Japan.

Moreover, on behalf of the Amarin team, our thoughts go out to everyone in Japan who is dealing with the devastation caused by these catastrophic natural events. We send our best wishes to all those who are affected.

In prior discussions, we have stated that we expect to have two additional suppliers online by the end of the year. That remains our target. It should be noted that our existing supplier continues to want to supply Amarin with all of the supply we need. While we have a very good track record with this supplier and we look forward to working with them for many years, we believe it is prudent to have multiple suppliers from a risk management perspective. We are in various stages of negotiations with these companies, with emphasis on production capability, quality and cost.

Finally, in response to investor questions, I want to comment on the recent reported stock sale activity by certain of our insiders. My comments will be limited by the fact that I cannot speak directly for investors' choices that they make relative to investments or choices of their own, regardless of their affiliation with Amarin.

The reported sales have been conducted under 10b5-1 plans, in which a third party manages the trades by the selling person, and sales as well made directly by the selling persons outside of 10b5-1 plans. The largest of the reported sales have been made by Abingworth, Sofinnova, and Orbimed, and represent small portions of their overall holdings. These are three firms in which venture capital investments were made in Amarin in the $70 million private placement announced in October of 2009.

That financing led to the transformation of Amarin into the cardiovascular focused company that we are today, and led to the commencement of the MARINE and ANCHOR trials.

Fred Ahlholm is Amarin's VP of Finance. He will now comment on Amarin's 2010 financial results.

Thank you, John. Yesterday Amarin filed its annual report on Form 10-K for the year ended December 31, 2010. While I'll provide some comments here regarding our financial results, you will find a more extensive discussion of our results in our 10-K.

This 10-K filing is Amarin's first annual report to be filed with financial statements presented under US GAAP. Prior to this year, Amarin was classified as a foreign private issuer for SEC reporting purposes. And we reported our financial results in accordance with international financial reporting standards, or IFRS.

For avoidance of doubt, all historical financial information contained in the annual report is presented in accordance with US GAAP, not just the results for 2010.

There are a number of differences in the accounting treatment for certain transactions under US GAAP and IFRS. As it relates to Amarin, the most notable differences concern the definition of derivative financial instruments and the accounting for such derivatives.

Prior to 2010, Amarin completed a number of financial transactions which resulted in financial derivative accounting. Although these derivatives are non-cash in nature, they nonetheless have an effect upon our statements of operations and balance sheets.

In particular, the warrants issued in connection with our October 2009 private placement are classified as a derivative liability under US GAAP, whereas they had been previously treated as an equity instrument under IFRS. These warrants contain a pricing and variability feature, whereby the exercised price of the warrants could increase, depending upon the exchange rate between the US dollar and the British pound.

Despite our belief that the circumstances required to trigger this price adjustment provision are unlikely to occur, and despite the fact that the number of shares which could be issued under the warrants does not change under any circumstance, the application of US GAAP requires that the warrants be classified as a derivative liability.

I am initially focusing this discussion on derivative accounting because the application of US GAAP to these warrants has had a pronounced effect upon our consolidated financial statements. Using a Black Scholes option pricing model, the Company has calculated the fair value of these warrants and recorded a warrant derivative liability of $230 million at December 31, 2010.

I would like to emphasize that this warrant derivative liability represents a non-cash item. Upon the exercise of the warrants, the fair value of the warrants exercised will be reclassified from liabilities to equity.

However, until all the underlying warrants are either exercised or expire, the fair value of this warrant derivative liability will be periodically remeasured, with the changes in fair value recognized in the statement of operations.

In 2010, this remeasurement resulted in non-cash charge to operations of $205 million. For avoidance of doubt, the maximum number of common shares issuable under the warrants as a result of the October 2009 private placement remains $36.1 million.

During the year ended December 31, 2010, $5.3 million of these October 2009 warrants were exercised, resulting in gross proceeds for the Company of $8 million. Because of the pronounced effective financial derivative accounting upon our statement of operations, the remainder of my comments regarding Amarin's financial results will focus on cash and cash flow.

Amarin's cash balance at December 31, 2010 was $31.4 million. This cash balance was augmented in January 2010 by $98.7 million in net proceeds received from a public offering of $3.8 million American depository shares or ADSs, where each ADS represents one common share.

During the three months ended December 31, 2010, net cash outflows were approximately $9 million, including approximately $6 million paid in connection with the Company's two Phase 3 clinical trials. Cash outflows for operating activities for fiscal year 2010 were approximately $33.9 million, as compared to cash outflows in fiscal year 2009 of approximately $28.4 million.

The increase in cash outflows in 2010 was due primarily to our two Phase 3 clinical trials, the MARINE and ANCHOR studies, for which enrollment began around the start of 2010.

During 2011, we anticipate that our G&A spending, excluding the effect of non-cash derivative accounting and stock-based compensation charges, will increase modestly as we accelerate our commercial preparations.

In January, we hired a chief commercial officer. We expect to add marketing staff during 2011 to support these commercial preparations with more substantial hiring anticipated for 2012, in the event that AMR101 is not partnered by that time.

Our R&D spending related to our MARINE and ANCHOR clinical trials is declining as these trials approach their completion. During 2010, we were billed for approximately $17 million by our CRO in connection with the MARINE and ANCHOR trials. We estimate that approximately $9 million remains to be paid to our CRO in 2011 for the completion of these trials, of which we have accrued approximately $3 million at December 31, 2010.

Although the cost for these clinical trials are expected to decrease during 2011, this decline in research and development spending would be partially offset by spending which could commence if we elect to build commercial inventory levels, of which certain costs may not be initially capitalized, or if we elected to commence an outcome study, the cost and timing of which is under evaluation.

The spending levels for certain activities, including the outcome study and commercial preparations, could be affected by our ANCHOR trial results and, therefore, we are not quantifying our 2011 spending forecast at this time. Regardless of our ANCHOR trial results, we anticipate spending on commercial preparations in 2011, and we may elect to do an outcome study to enable us to seek a cardiac protection indication.

Amarin has 125.5 million common shares outstanding at March 15, 2011, which includes the 13.8 million shares issued in the January equity offering and approximately 4.8 million shares issued in 2011 year-to-date for stock option warrant exercises.

In addition to filing our annual report, we plan to file various registration statement-related documents. The majority of these filings terminate existing obsolete registration statements. After the termination of these obsolete registration statements, we also plan to file a new shelf registration statement as we believe it is good financial management to always have an effective shelf registration statement in place.

We were prohibited from filing a shelf registration in recent months due to our transition from IFRS to US GAAP. Amarin plans to be active at investor conferences with upcoming presentations scheduled at the Needham Healthcare Conference in New York City April 3 through April 5, the BioCentury Future Leaders Conference on April 15, also in New York City, and the Deutsche Bank Healthcare Conference in Boston May 2, 3 and 4.

Thank you for your attention today. That concludes our prepared remarks. We will now open the call to questions. Operator?

(Operator Instructions) Joseph Schwartz, Leerink Swann.

Good morning and congratulations on all the progress. I was wondering if you could remind us how long it took you last time in the MARINE study from the time the last patient received their last dose until you were able to report the results? And are there factors that you think would make that duration quicker or longer in the ANCHOR trial?

Hi, Joe. It is Joe here. I am going to ask Paresh if he wouldn't mind taking that question.

Hi, Joe. The last time it was about five weeks or so from the time we had the last patient visit until we had the data. Now if you recall, the MARINE study was 229 patients and we had about 50 sites. And the main determinant is basically a number of sites because you will close down all these sites, get the data back from the sites to the CRO.

We have more than 80 sites in the ANCHOR trial. And while it is a US only trial, as you know, there is a lot more sites and we have got about 2.5 times the number of patients that we had in MARINE. So there is a lot of data coming in. We have a large number of endpoints, many of them (inaudible), but we have to close all of that out and close the database before we actually even unblind the data.

We also have to ensure that we have decided which patients meet the criteria for (inaudible). So there is a lot of paperwork to be done, (inaudible) to sign off, and there is a fair amount of work to do for a pivotal study. And of course, we have to ensure that the quality standards are met in terms of the regulations so that if the sites are audited, they meet the quality standards.

That is very helpful, thanks. A lot of anecdotal evidence points to the lack of an LDL increase on EPA. And there has been some new signals in MARINE that you might see some synergy with statins. I would love to get your thoughts mechanistically on why this may be the case.

As I said in our previous conference call, we were surprised to see that result, surprised but very pleased. I think it bodes very well for the ANCHOR study that the combination of statins with the EPA for good efficacy, ethyl EPA used a lot. In the ANCHOR study, as you know, all patients are on statins.

We have some preliminary evidence and some scientific literature to show that when you combine statins, certain statins with EPA, you get enhanced gene expression of HMG-CoA reductase, and that has been published in papers a few years ago. It is an individual study but it's (inaudible) become synergy.

In addition, we have done in vitro studies and we hope to be presenting that this year at meetings, looking at an in vitro [top] model of EPA, DHA separately, both in combination with statins and statins alone. And that seems to indicate also that when you combine EPA with -- and this starts with atorvastatin. When you combine EPA with atorvastatin, there appears to be greater inhibition of lipid peroxidation.

So, in fact, that could be really interesting if that translates to an in vivo effect, a clinical effect. We are looking forward to the ANCHOR result to help us understand that better.

There also could be some differences in LDL statin sensitivity to EPA and DHA that has been talked to many times. These are all theories, as you know, and we look forward to do some mechanistic work in the future after we get the results on the (inaudible).

Very good. Thanks again.

Thomas Wei, Jefferies & Co.

Thanks. Just wanted to clarify a couple of things that you had said on the call. The third-quarter filing guidance, does that assume -- is that independent of whether or not you filed just on MARINE, or if the two datasets go in together would there be some shifting of the timeline if you decided to file with ANCHOR as well?

Hi, Thomas. This is Joe. Thanks for the question. What we tried to do today with this is we have the data; we know MARINE; we have gotten more and more comfortable. And we basically said, look, we want to give this message to The Street. Everyone has been asking when in 2011 might you file.

So our first point is we scrubbed the data; we have done everything; we are on our path to a Q3 filing, boom. Now depending on what ANCHOR has or doesn't have, we could say the data looks great. We actually want to file them both together in Q3. We may actually say, no, we want to go Q3 followed with the MARINE, followed by the ANCHOR later. And that's a discussion we are still having.

And again, a lot of that will depend on where we end with our partnering activities, etc., different preferences that people have. But what we are trying to do is keep our degrees of freedom open and at the same time reporting to yourselves, The Street, etc., what our current expectation is to give a little greater clarity.

And the FDA request that an outcome study be substantially underway, could you just clarify for us, is that underway at the time of the filing or at the time of approval? What is your current interpretation of what substantially underway means?

Well, I'm going to let Paresh answer that, if you would.

Sure. Hi, Thomas. First, let me just add one comment on the outcome study. We believe the outcome study has huge value to AMR101. Cardiologists that we have spoken to really want to see outcome data in addition to the (inaudible) biomarker data. And this applies to all lipid biomarkers, not just triglycerides.

And we believe that we have a lot of confidence that -- it will demonstrate a lot of confidence in our product in starting that study and showing that we believe that this will be done.

The JELIS study, as you know, showed benefit in low-risk population plus it showed a benefit in multiple high-risk groups within that population, and still the only study to show benefit on top of the statins.

The FDA wants us to have a study -- if we are seeking the MARINE (inaudible) indication, then at the time of submission for that indication, whether it's an sNDA or part of the initial NDA, we need to have the outcome study well underway. We are working with them to define what that means in terms of how many patients they need to see enrolled in the study.

However, they have said to us that they do not need to see the data readout before they give us the indication if the ANCHOR study is positive and the study is well underway and they are comfortable with our proposal, they would give us the indication.

They also do not need to say any interim analysis or any safety analysis in order to give us any information. So we are still working with them, but we need to have that underway by the time we send in the submission for the ANCHOR indication.

And then just lastly, something on ANCHOR that I wanted to ask you about. So if you just kind of look globally at the two different targets that you are trying to reach in ANCHOR, the triglyceride endpoint and the LDL endpoint, which do you think is the riskier endpoint in ANCHOR? And then separately, how is the dropout rate looking relative to your original powering assumptions? Thanks.

Let me take the second question first because it's easier. We actually had a lower dropout rate than we predicted. So that obviously helped our power calculations and the amount of power we have in each treatment group. We predicted about 10%, and we have much less than that.

In terms of the confidence, I think I am confident in both the endpoints. Obviously, we need to wait for the data. But based on the MARINE trial results, whichever way we cut the data, we see no increase in LDL compared to the control group.

And in addition, we see lowering of triglycerides not just in the primary cohort but when we did multiple -- (inaudible) testing of multiple comparisons. We still saw it in the 2-gram group when we looked at subgroups (inaudible), when we looked at subgroups with statins, all pointing to very encouraging signals for ANCHOR. So I'm confident about the endpoints, Thomas, for that.

Thank you.

Chris Hamblett, Cowen and Company.

Thanks for taking the question, guys. What would be the projected size and length of the outcome study if you do need to do that?

I would like to just make a comment and then turn it over to Paresh if he wants to. We are still working through that with the agency. We think it is less than 10,000 patients, I would say. These are usually five-year studies.

Interestingly, their spending is spread significantly over that time period in a very sort of proportional way. So we actually, as we look at it more and more, get more and more excited that while we think this is something we really want to do with a partner, we actually have the wherewithal given our current position and where we are at, assuming positive ANCHOR data, to do that study ourselves if we needed to.

And I think a lot of that goes to the great work by Paresh and his team at understanding the parameters there and working with the agency. So again, I say less than 10,000 patients. I would say a five-year period of time. I don't know, Paresh, if you wanted to add anything?

Thanks, Joe. I think you have covered most of it. Just to add one quick point, we are not looking at a JELIS type population. A JELIS population is low risk with a low event rate and they had 18,500 patients. We are looking at a high-risk population doing it mainly in Western countries and, therefore, we are expecting a higher event rate.

So it's obviously much smaller than JELIS and probably a shorter duration of follow-up. But the main thing is to get enough events to have enough power (technical difficulty).

That is fair. Then in terms of -- are you interested in other combinations beyond statins potentially?

I think there is a lot of degrees of (inaudible), Joe, that you can go to, a lot of opportunities. I can just rattle off 5, 6, 7 drugs, but I won't do so for practical reasons here, but there are a lot of areas for combinations. There are a lot of areas for other indications.

There are a lot of other very interesting trig-lowering safe drugs out there possibly to look at. So we think there is a lot of expertise here that has been built at the Company, and we think that what we have is the ability to really drive the exploitation of these opportunities in the trig-lowering franchise building, if you will.

Lastly, do you think you'll have data presented at ACC this year, or is that unknown?

The ACC is coming up April 2 to 5; is that correct? Yes, I think we are going to be at ACC. We have got a booth, we have got a number of things going on. I don't think we got in for the -- we were late to the late-breakers submission process. We will be there. We will be heavily in attendance, but I don't believe that we are on any formal sessions.

Okay, thank you.

There are no further questions at this time. I will turn the conference back to management for closing remarks.

Again, thank you, everyone, for your interest in Amarin and for your time today. The team has done a phenomenal job in the past 12 months to get us to where we are from where we were just a short time ago in October of 2009.

And it has been my pleasure to work with the group and it is my pleasure to work with them going forward to really build this team, this Company, out to what its full potential can be, either with or without a partner. So thanks. We look forward to presenting the data on ANCHOR as it comes available in Q2 this year, and keeping you updated of our progress. Thank you very much for your time today.

Thank you. This concludes today's conference. All parties may disconnect now.