Amarin Corporation PLC (AMRN) 2006 Q4 法說會逐字稿

Good morning. My name is Beth and I will be your conference operator today. At this time, I would like to welcome everyone to the Fourth Quarter Earnings Conference Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. [OPERATOR INSTRUCTIONS].

Thank you. Ms. Fields, you may begin your conference.

Thank you. Good morning. This is Anne Marie Fields with Lippert/Heilshorn & Associates. Thank you all for participating in today's call. Joining me from Amarin Corp. are Rick Stewart, President and Chief Executive Officer; and Alan Cooke, Chief Financial Officer.

Earlier this morning, Amarin Corp. announced financial results for the fourth quarter and fiscal year ended December 31, 2006. If you have not received this news release or if you would like to be added to the company's distribution list, please call Lippert/Heilshorn in New York at 212-838-3777, and speak with [Lydia Portia].

Before I begin, I would like to caution that comments made during this conference call by management will contain forward-looking statements that involve risks and uncertainties regarding the operations and future results of Amarin. I encourage you to review the company's past and future filings with the Securities and Exchange Commission, including without limitation the company's Form 20-F and 6-K, which identifies specific factors that may cause actual results or events to differ materially from those described in the forward-looking statements.

Furthermore, the content of this conference call contains time-sensitive information that is accurate only as of the date of the live broadcast, February 8, 2007. Amarin undertakes no obligation to revise or update any statements to reflect events or circumstances after the date of this conference call.

With that said, I would like to turn the call over to Rick Stewart, Rick.

Thank you, Anne Marie. Good morning everyone and thank you for joining Amarin's fourth quarter and fiscal year end 2006 conference call. 2006 was a year of great accomplishment for Amarin. Obviously, the focus has primarily been on the conduct of our Phase III clinical trials in Huntington's disease, but many other key milestones have also been met.

As you may have seen, the completion of the two Huntington's disease trials was announced last Monday. This is a major landmark for the company. And attention now turns to data validation, verification, and ultimately, data release.

The most significant achievement in 2006 is clearly the successful completion of recruitment on schedule, plus the overall conduct of these extensive trials. The 600-patient Huntington's disease clinical trial program represents the largest therapeutic study ever undertaken in Huntington's disease. An immense effort was involved to progress from commencement of recruitment to completion of the trial in less than 18 months. We are eagerly anticipating the headline results in the second quarter.

In addition to the advances with our Huntington's disease clinical program, we achieved several other objectives. We successfully in-licensed a novel oral apomorphine product and significantly progressed its development during the year. We reported promising preclinical data for Miraxion to treat Parkinson's disease and also melancholic depression. We advanced the commencement of an innovative Phase II neuroimaging trial in Parkinson's disease and made progress in melancholic depression.

We commenced Amarin's preclinical Combinatorial Lipid Programme with the selection of the first two product candidates. And importantly, we raised, in aggregate, $25 million to fund the development of these new programs.

The result of the effective execution of our strategy was that Amarin's share price outperformed the majority of its small-cap and mid-cap tiers, growing by 90% during 2006. Over the last 2.5 years, members of our Management and Board have invested $16.2 million in Amarin's financing, underscoring their belief in the future potential of our franchise and confidence in our strategy to build value.

Before I speak more about our accomplishments and future outlook, I am going to turn the call over to our Chief Financial Officer, Alan Cooke to review our financial results. Alan?

Thank you, Rick. The net loss for the fourth quarter was $6.5 million and for the year it was $26.9 million, which represents an increase over 2005. The main driver behind this is the significant increase in our investments in research and development, which effectively doubled to $5.1 million in Q4 and $16.5 million for the year when compared to the comparative periods. This reflects the cost of the two Phase III trials in Huntington's disease and the development cost of our novel oral formulation of apomorphine.

Selling, general and administrative costs were $2.9 million and $11.8 million for the fourth quarter and full year. They include, in addition to general corporate overheads, a substantial investment in intellectual property, and the business and corporate development costs for pursuing our growth strategy, including a significant level of professional fees, and the cost of evaluating acquisitions and in-licensing opportunities.

The increase in SG&A costs over 2005 is primarily due to increased professional fees and staff costs. SG&A costs have been relatively flat quarter-to-quarter through 2006.

The net loss also includes a non-cash charge with respect to share-based compensation. The non-cash charges in the fourth quarter and full year were $0.5 million and $2.2 million.

Let me address Amarin's capitalization and our cash position. Over the course of 2006, Amarin raised gross proceeds of $25 million for the issuance of new equity. At December 31, '06 Amarin had cash of approximately $36.8 million and no debts. Amarin is at a strong financial position and well positioned to advance its pipeline Huntington's disease, melancholic depression, and Parkinson's disease, and to execute its strategy of supplementing its internal pipeline for the acquisition and in-licensing of other exciting new clinical stage programs in the field of neurology.

At December 31, Amarin had 90.7 million shares outstanding and approximately 19 million options and warrants. Amarin has a broad shareholder base, approximately 27% of the company is held by directors and officers, who have invested over $16 million in Amarin in past 2.5 years. Approximately, 50% is held by institutions and investment funds predominantly in the US, with the remainder estimates to be held by retail investors in the US and Europe.

With that, I'll turn the call back over to Rick.

Thank you, Alan. Let me begin my remarks by reviewing in more detail the progress made with Miraxion in Huntington's disease. As I said earlier, the most significant achievement for 2006 was the successful completion of recruitment on-schedule and the overall conduct of our Phase III trial of Miraxion in Huntington's disease. Completing this large 600-patient clinical program and an Orphan indication in less than 18 months was a formidable task.

These were sophisticated trials using advanced screening and recruitment techniques based on Amarin's internal experience, combined with that of the Huntington Study Group, and also the European HD Network, which was formerly known as Euro-HD. It was critically important to ensure that only Huntington's disease patients with the correct genetic profile and disease severity were enrolled into the trials.

As our earlier Phase III clinical trials have demonstrated the patients with lower CAG scores and less severe disease were more likely to respond to treatment with Miraxion. Additional safeguards into the trial conduct were introduced, including increasing the number of patients in the trial from 135 in the first trial to over 600 combined in these trials, increasing the centers from 6 in the previous trial to 70 in the combined trials, and improving the quality and frequency of both assessments and patient monitoring.

We also took the prudent step of obtaining a Special Protocol Assessment, which was agreed with the FDA prior to commencing the trials.

Finally, and potentially most importantly, we sought the advice and guidance of our leading experts in the field of Huntington's disease, namely the Huntington Study Group and European HD Network.

Ensuring we included only patients with a correct genetic profile and disease severity was perhaps the biggest challenge. To refresh your memories, the earlier 135 patient Phase III trial identified the per-protocol patients with CAG scores of less than or equal to 44 demonstrated a 22.7% improvement in the TMS-4 scores versus a placebo-group deterioration of 5.7%, a difference of 28.4% over the 12-month trial.

These patients experienced the quality of life improvement of up to three years and then stabilized. The goal of the new trials was to replicate this CAG less than or equal to 44 per-protocol response in a larger patient population.

After detailed discussions with HSG and FDA, it was decided to use phenotypic or clinical symptoms as the inclusion criteria to the trial rather than the genetic profile. The genetic data or CAG scores were collected at enrollment. A sophisticated algorithm was developed by HSG for patient screening, based on phenotypical clinical symptoms as a proxy for our genetic test.

When tested against the HSG's 4,500-patient registry, the algorithm showed that approximately 7% of the patients enrolled in for trial would have CAG scores of 44 or less, and approximately 30% higher, but predominately up to 48. No patients would have severe disease. We cannot underestimate the role of the Huntington Study Group, European HD Network, and ICON, our CRO, have played in the successful recruitment and treatment of patients in this trial. I thank the dedication of the clinicians who are conducting the trials with such efficiency. This was truly a collaborative effort with significant contributions from all parties.

In many respects, the earlier trial was groundbreaking, because significant new information was identified from the outcomes. As I mentioned, limiting the inclusion criteria to less severely ill patients and those with lower CAG scores gives us greater confidence of obtaining a positive outcome in the current trials.

Importantly, the earlier trial was effectively 24 months long. The first 12 months was a double-blind placebo controlled trial. The second 12 months was an open-label phase, when all patients who have been on placebo were eligible to take Miraxion. All but one of the 121 Huntington's disease patients, who were eligible to proceed on to the open-label phase, actually did so.

When we examined the TMS-4 scores at the end of the open-label period, we identified two key findings. Firstly, those patients, who have been on Miraxion for the entire 24-month period maintained their TMS-4 improvement through the open-label phase.

Secondly, as expected, the placebo patients who switched to Miraxion for the open-label phase demonstrated a comparable improvement in TMS-4 score as those who have been on Miraxion for the first 12 months. We are still treating the vast majority of these patients on a name-patient basis from this earlier trial. These data gives us more confidence and the positive outcome of this kind of trial. As you've seen from our recent announcement, the treatment phase of our current trials has now been completed and all patients may now switch on to the open-label extension trial.

Currently, we are completing the data collection, validation and analysis process for each of these trials. Later, we will conduct a cross validation of the two databases, US and Europe, to ensure the consistency and the integrity of those databases. This is painstaking work which leads to the final analysis of the data. It is critical with the two databases are treated in the same way so that we can ultimately conduct a meta-analysis of the 600 patients in both trials.

We would expect that this process should be concluded by mid-second quarter when headline results will be released. We would expect to present the data in its entirety at one of the major neurology conferences later in the year.

Our priorities in the short-term are to firstly successfully complete the data analysis in our Phase III trials; secondly, on receiving good data to prepare to the commercialization of Miraxion; and finally, to lay the foundation for the expansion of our Miraxion franchise into Parkinson's and other neurodegenerative diseases.

Positive data will allow the acceleration of our plans to conduct further clinical trials in other chronic neurodegenerative diseases, while there are few treatment options. Amarin's current plans are to commercialize Miraxion in the US by our small highly qualified sales team, which will focus on those neurologists who are members of the HSG plus other high prescribing Huntington's disease and movement disorder specialists.

The sales team will be highly qualified and would be geared towards continuing medical education programs. We currently estimate that a few of them, 25 sales personnel, will be required along with a strong marketing operation.

As part of our commercialization planning, we engaged a well-known consultancy company to develop an initial pricing strategy for Miraxion to treat Huntington's disease. We have previously used the $10,000 per year cost of Rilutek for the treatment of Lou Gehrig's disease as a benchmark for Miraxion when building our own internal financial models.

That price expectation now appears to be on the lower end of the pricing range as determined by the pricing specialists. Obviously, final pricing decisions will be made on the basis of if and how well the drug actually works in Huntington's patients. However, we do see substantial potential upside on the conservative market opportunity of 500 million that we had been forecasting.

The annual pharmacoeconomic cost of Huntington's disease is estimated to be around $2.5 billion annually with individual patient costs increasing substantially in the more advanced stages of the disease when patients are admitted to nursing homecare. The current standard of care for Huntington's patients is antidepressants, antipsychotics, pain relief and muscle relaxants, none of which are specifically indicated for this terminal illness.

Just to go through those timelines again. We plan to release headline data in mid-second quarter and expect to complete the NDA filing with the FDA in the third quarter. As Miraxion has Fast Track designation with FDA, we were anticipating priority review which could lead to a response from FDA to the filing in early 2008. Our goal will be to launch Miraxion for the treatment of Huntington's disease as soon after FDA approval as possible.

Turning now to Miraxion for melancholic depression. We now have a better understanding of the mechanism of action in this disease and have identified a trial design which mitigates some of the risks traditionally associated with the depression trials of this nature. As with Huntington's disease, we've engaged with some of the leading experts in the field of melancholic depression for guidance on trial design. Let me briefly recap our data in this indication.

262 depressive disorder patients were involved in three sponsor-led Phase IIa studies. Post-hoc analysis showed that 137 of these patients have melancholic symptoms and demonstrated a positive response to Miraxion treatment, whereas previous treatments had limited effect. Melancholic depression has very specific and unique symptoms, which are identified by DSM-IV, the Psychiatric Bible. These symptoms include anhedonia, which is a failure to response at any traceable stimuli, psychomotor disturbances, anorexia, excessive guilt and speak disturbance. Sadly even today, in extreme cases, current treatment remains electroconvulsive shock therapy, which is effective to six months or so, but which has serious consequences.

The results from melancholic depression patients in these trials are being evaluated by key opinion leaders, who are encouraged by the response seen. Additionally, and in order to validate the findings from these relatively small trials, we retained a statistical analysis company, which conducted a meta-analysis, converting the assessment measures such as the Hamilton Rating Scale, Montgomery-Asberg, and Beck Depression Inventory into a common currency called effect size. This allows a direct comparison of the results, which validated the significant response seen in melancholic depression patients.

Thinking about trial design in melancholic depression has been influenced by the recent disappointing results in other small depression trials. In particular, we have been influenced by the unusually high placebo effect causing unexpected outcomes.

We now expect to conduct a Phase II trial in melancholic depression patients using both biomarkers and efficacy endpoints. This approach will enable us to gain a clear understanding of Miraxion's impact or the chemical imbalances in the brain which are the underlying cause of the disease, and provide data to identify additional characteristics of patient responders. Careful trial design and accurate targeting of the correct patients is the key to success.

Turning to our developments in Parkinson's disease; the results of Amarin's preclinical program in Parkinson's disease demonstrated the same mechanism of action as Huntington's disease; that is the stabilization of mitochondrial cell membranes and the slowing of apoptosis. It also showed increases in Brain-Derived Neurotrophic Factor. We will commence in the near future a highly sophisticated Phase II Parkinson's disease neuron-imaging study utilizing Functional Magnetic Resonance Imaging incorporating quantitative [tractology] techniques, allowing researchers to identify both function and activity of Miraxion in Parkinson's patients in a nigrostriatal pathway. It is one of the four major dopamine pathways in the brain as particularly involved in the production of the movement.

Loss of dopamine neurons in the substantia nigra is one of the main pathological features of Huntington's disease, leading to a mass reduction in dopamine and motor function. This is important because we will be able to identify this specific impact Miraxion is having in stabilizing mitochondrial activity in Parkinson's disease patients. We are looking forward to commencing this study during the second quarter of 2007; I would expect to have an interim analysis available later in the year.

Saying that oral apomorphine as a rescue therapy to Parkinson's patients; in May of 2006, we announced the acquisition of the global rights to a novel oral formulation of apomorphine absorbed sublingual or under the tongue for the treatment of off episodes off semi-paralysis in Parkinson disease patients. We believe this acquisition offers a very exiting opportunity for Amarin as it expands our product development portfolio and underscores our commitment to the development of novel therapeutics to treat neurodegenerative disease.

Current standard of care with these advanced Parkinson's patient experiencing frequent off-periods is a highly painful and frequent subcutaneous apomorphine injection, which limits the utility of the drug.

Key Parkinson's disease thought leaders have reacted favorably for an oral alternative which overcomes many of the drawbacks of the injectible.

In mid 2006, a proof of concept study using an early sublingual formulation of apomorphine was conducted in volunteers, which demonstrated oral bio-availability.

Towards the end of 2006, a pharmacokinetic study using several different formulations was commenced. This trial is intended to identify the differing absorption characteristics from the formulations in order to identify compounds to optimize with a view to commencing a Phase II efficacy trial in Parkinson's patients later this year. The market opportunity called sublingual apomorphine could be substantial, with revenues potentially exceeding $100 million in the U.S. alone. Current apomorphine sales related to the subcutaneous injection are minimal due to painful and inconvenient route of administration.

And finally, I would like to turn the attention to our research programs which don't always get the credit they deserve. There are two key areas of research ongoing; firstly, further investigation of Miraxion in other neurodegenerative diseases such as Parkinson's and the aging brain. Research is being conducted at the University of Prince Edward Island, and the Institute of Neuroscience at Trinity College, Dublin, respectively.

Secondly, continuing work on the Combinatorial Lipid Program which has made real progress during the past year. The Combinatorial Lipid Program combines or more accurately chemically conjugates bioactive lipids with either other lipids or existing drugs to improve bioavailability while brain barrier penetration and potentially increase efficacy while reducing side effects. This is very exciting as each conjugate will be a new chemical entity with the potential for new intellectual property. The application of this platform is not just limited to neurology but also having applicability across a range of indications from cardiovascular to oncology.

The first two candidates have already entered into a preclinical programs and preliminary evidence suggests that the combinatorial lipid version of our Parkinson's disease drug may have certain and specific advantages over the currently available form. We will provide further information when the final results are available.

So with that, I'd like turn the call back over to Beth for questions and answers.

[OPERATOR INSTRUCTIONS] Your first question comes from the line of Ian Hunter.

Good afternoon gentlemen. Just a couple of questions here first, and then I will get off and let other people ask. First of all, I was just wondering that the trials are completed in the U.S., just wondering how many patients, can you give us an idea, actually completed the trial? And how many have switched on to the open-label study post the trials finishing? And then, as a kind of follow-up on that, what portion of the Q4 '06 R&D spend was related to those two trials and can we see that coming off a bit in the next couple of quarters or will that be picked up by other programs coming through the system?

I will answer the first one, Ian, and then I'll hand the second one on to Alan. At the present time, we don't actually have the final roster of completers in the trial. Our real expertise, I mean there's a slight difference between the overall completers in the trial and also the protocol compliance as well. We won't know what the number of protocol compliance was until we unwind the study later on.

In terms of withdrawals, we had already budgeted for round about 10% withdrawals, and what I can tell you is, the level was substantially lower than that. But we are still finalizing those final numbers. But it's in the order, I would think, between 5% and 7% versus the 10% that we forecast. Clearly the more patients that are completing the trial, the better. I hand the second part over to Alan.

Hi Ian. On the R&D cost and the run rates, we were running at about Q3 and Q4 on R&D about $5 million or so for last two quarters. As we move through 2007, R&D expenses will definitely fall and with that the Huntington's disease trials winds up and there are open label continuing to cut that expenditures, somewhat offset by that. And also, of course, by the three Phase II trials that we expect to commence in coming months in melancholic depression and Parkinson's disease, and also with apomorphine. But I think the increase from those trials will not fully offset the flow from HD to our expenditure.

Yeah, okay, that that's great. Maybe just can -- a quick follow-up question here. I was just wondering as you have cash there, maybe the expenses have come off a bit. You did mention there in licensing of other programs or potential acquisitions, and I am just wondering if you could give us an idea of what the indications will be if you are looking to bring drugs in and at what stage in that process of development you will be looking at? And maybe a feel what the general environment is out there for early-stage drugs?

Ian, I will start off on that, Alan will chip in. I will do those in reverse orders as most politicians do. If you look at the overall landscape for in-licensing opportunities, there is no question that it is difficult. I think it's difficult in two key respects. The first one is, actually identifying quality opportunities where there is a well-defined probability of a successful outcome. Clearly, the earlier you are in the process, the more risk adjusted it has to be. But I think the other aspect to it is, what is the cost of these? As you have probably seen, there are some very substantial numbers which are being paid for in-licensing opportunities at relatively early stages.

And quite frankly, we are not in that business of writing checks for tens of millions of dollars for earlier stage compounds. What we are in the business of doing is very selectively identifying very interesting opportunities where we are able to either co-develop with the original developer or provide some other capability within our own organization, which will enhance the probability of success. So I just want to reassure you, you are not going to see us out there writing very substantial checks upfront for in-licensing opportunities. Does that answer your question, Ian? Ian, are you there?

Ian must have dropped off. Beth, is there any other question?

Your next question comes from Steven Handley.

Good afternoon. Two things, first of all, why don't you, in fact, be a little more specific about the range of R&D spending that you would expect this year? You mentioned on balance part, it would be down from last year because of the Huntington's disease trials decline would be more than the offsetting -- partially offsetting increases elsewhere. Could you mention -- just give us a range of what you would expect this year? And secondly, I would appreciate you repeating the -- I couldn't quite get all the comments you made earlier having to do with the pricing considerations related to Miraxion. You indicated that you would probably assuming everything continues to come out fine on the clinical validations, et cetera that your thoughts now are that pricing would be somewhat higher than earlier, and you had some reference points and comments that I have frankly missed a little bit.

Steven, let me hit the R&D spend. I can't be too specific in terms of what I can tell you for what we will spend in 2007 simply because the timing of the trials and the ultimate design of some of the trials which haven't been completely met at this point, will determine the exact spend. But, I think it's suffice really to say at this stage given from the [inaudible] costs, our expenditure should come down in the levels we've seen in Q3 and Q4 as you run through 2007. I think, once we get possibly into second quarter, I can give you better picture for the full year. But, I would expect our total R&D spend for 2007 to be lower than 2006. Rick, do you want to address the pricing?

Yeah. On the pricing, our internal forecasts had always been based on Rilutek for the treatment of Lou Gehrig's disease, as a suitable comparator and that is round about $10,000 a year. However, there are some distinct differences between Rilutek and Miraxion. And so far as Rilutek really only extends survival by round about 12 weeks whereas our intention is that Miraxion will have a much more profound impact on the overall symptoms of the patients. So, as we went out with a leading pricing consultancy to evaluate the real potential pricing models for Miraxion, what we found was that there was a potential opportunity to price the drug. And again, as you said, it depends on the results and the efficacy of the drug, but to price the drug substantially higher than our expectations. I can't give you the exact pricing because that will be predicated on ultimate discussions with reimbursement and FDA. But all I can say is that the numbers that we were looking at were significantly higher than those that we've been quoting in the past.

Now, I think that those earlier numbers were reasonable in so far is using Rilutek as a benchmark was as good a comparator as any, but now that we've got a much more fundamental understanding of the dynamics of the disease, the cost -- the current treatment to these patients that a higher price point may well be an opportunity.

As your total cost to develop the product expanded so far and then anticipated to finally get this through the FDA, have they been in line with your earlier expectations or might a higher price in a modest way be justified by higher cost that you've incurred to develop it?

Well, I think the cost incurred, Steven, has been probably in the [rank] where it is expected, so I think it's the -- on the pricing side, it's the comparable cost as you can see for therapeutic discount, and there has been substantial spends on Miraxion since its conception and since as go through the preclinical and clinical development program, we've encouraged significant amount of expenditure and safety program, as Rick has mentioned, is the biggest aggregate undertaken for therapeutic for Huntington's disease to invest it very significantly in this orphan drug.

I think there is another, and two aspects really are reaching to the initial R&D spend plus return, but also I think probably more important is to focus on the current cost of care for Huntington's disease patients. Now, it is extremely difficult to get a well-validated number, but I think it would be fair to say that anything between say $75,000 and a $125,000 a year, depending on the stage of disease progression is a relatively well-founded number. So, that if you had a treatment which showed a similar kind of response to the CAG less than 44 protocol group in that earlier trial improving the quality of life by three years and stabilizing it there. The pharmacoeconomics of the drug like that would be substantially better than the current cost of care.

Okay, thank you.

Your next question comes from the line of Jack Gorman.

Thank you very much. Guys apologies, if I am crossing over on questions here, I was off the line for a couple of minutes, but I have kind of one broad question and two perhaps housekeeping questions. Maybe firstly on the housekeepings, your interest in other income line saw a little bit of spike in Q4. Just wondering if there was anything in particular driving that? And also your net cash balance as of the end of the year was a little bit better than our own forecast. And I am just wanting to a sense on the cash flow, whether there were any -- kind of one-off items running through in Q4 that might have accounted for that?

That's not really the [actual scene]. The cash flowed and that was exactly much via the cost incurred. And in terms of the interest and other lines, we do have -- we hold our cash in sterling and in US dollars and a small amount in euros. And we don't take any foreign currency with -- to the extent that we [can't afford]. We -- as soon as we raise cash, we traditionally translate it immediately into the currency, with which we expect to incur the expenditure in the coming months not with the -- our [inaudible] funding from the last three years. So, at the end of the year, on December 31, we would host our estimates in sterling, in cash. From an accounting perspective then, you've got to translate that back into dollars. [It should be around $2,000]. And there is a typically -- the way the dollar has moved in recent months and quarters, there has actually been an exchange gain, which hits the markets, the interest, and other lines.

Great.

And it's a non-cash item.

Great. And just as a broader question, and perhaps, Rick, you kind of have partly addressed already in your earlier comments, obviously the focus as regards to primary endpoints for Miraxion in your HD trial is the TMS-4 score. But, obviously, as we know from a HD perspective, there are number of other kind of aspects to the disorder from -- cognitive and functional point of view as well. I just wanted to get a sense of how you are addressing those other elements of the typical HD patient? And also, what your sense of the FDA's expectations will be on what the data will show in that regard?

You are quite right. I mean the primary endpoint is affectively a movement dysfunction endpoint, and we're looking for an improvement in that. But clearly the cognition and behavioral aspects of the disease are ones that need to be taken into consideration and they are dealt with in our secondary endpoints in the trials. So, we're taking assessments of any improvement in cognition behavior as we go along. I think the benefit of that is quite simply. We are collecting a vast amount of data on an individual patient basis from the trial. In terms of the FDA's expectations, clearly the TMS-4 is the chosen primary endpoint. And assuming we get because it's still significant with that, then we're in very good shape. However, I would suggest that, it was an improvement, mass improvement in cognition and behavior, the FDA would also take that aspect into consideration as well. As always when you chose your primary endpoint, you have take great care and that is, that's the way we design the trials. But it may well be that we are going to see improvements in cognitional behavior as well. So, discussions with the FDA has centered mainly on the TMS-4 Score. We haven't really explored the impact of a secondary to this date.

And Rick, sorry just it may be premature, but to the extent to which you are successful in the trials and discussions obviously began as regards to labeling. Even in terms of your own ambitions as regards to label. Do you think you would require very good results on your secondary endpoints to get a broad label as regards the treatment of Huntington's disease in overall terms?

Yeah, that's an overall bonus I have to admit, what we are looking for -- I mean the ideal label we're looking at the moment is Miraxion for the treatment of the symptoms of Huntington's disease in mild to moderate patients.

Yeah.

And that would encompass certain aspects of the behavior on cognition, but frankly we are looking primarily at the movement dysfunction. Having said that, evidence of cognition and behavioral improvements in the earlier trial, there were some there, but it didn't come through as clearly as one would like to make any claims about it. But it may well be that because this trial is being conducted in such a well defined manner, with such targeted Huntington's patients, and that any cognitive and behavioral improvements will become much more apparent just because the trial has been conducted in a more professional way.

Absolutely, and I don't know if you can answer this, but has the FDA given you any specific kind of hurdle rates that you may require on the secondary endpoints and so that the kind of ideal label would be considered?

No, there has been no specific discussions around the secondary.

Okay. That's great, thanks a lot guys.

Thanks John.

[OPERATOR INSTRUCTIONS]. At this time there are no further questions.

Okay, if I can just look forward rather than backwards and turn to 2007 objectives, it's certainly going to be a busy year. As I said top-line results from the Phase III trail should be available in mid Q2. Assuming the data is received, we will aim to file the complete NDA package in the third quarter of this year. We will also support our European licensees with the European regulatory filings. On receipt of good data, we will implement our U.S. commercial strategy in anticipation of the launch, as soon as possible after FDA approval.

Additionally, we expect to conduct three Phase II clinical trials this year; in Miraxion for Parkinson's disease that's the neuro-imaging trial, Miraxion for melancholic depression; the targeted biomarker and efficacy trial; and finally, sublingual apomorphine for Parkinson's disease off-periods. We will continue to develop our research activities focusing on the Combinatorial Lipid Program and also committing to cutting-edge research in Parkinson's and other neurodegenerative diseases.

And finally, we will seek to expand our development pipeline by in-licensing additional products to the portfolio. We look forward to speaking to you again when we report our first quarter results later in the year. Thank you very much.

Thank you for participating in today's conference call. You may now disconnect.