英賽德 (INCY) 2005 Q1 法說會逐字稿

Good morning, ladies and gentlemen and welcome to the Incyte Corporation first-quarter 2005 financial results conference call. At this time all participants have been placed on a listen-only mode and the floor will be opened for your questions following the presentation.

It is now my pleasure to introduce our host, Ms. Pam Murphy, Vice President of Investor Relations and Corporate Communications.

Good morning. Thank you for joining us. With me today are Paul Friedman, Incyte's President and Chief Executive Officer; and Dave Hastings, Incyte's Executive Vice President and Chief Financial Officer. We will begin today's call with an update from Paul regarding recent progress in our lead drug discovery and development program, Reverset, CCR2, and our sheddase inhibitor, which recently entered Phase 1 development.

Dave will follow with a brief overview of Incyte's first-quarter financial results that were described in full in our press release issued earlier this morning. We will then open up the call for Q&A.

Before beginning, we would like to remind you that the prepared statements that management will be making during the conference call and statements made in response to questions will contain predictions, estimates, and other forward-looking statements that are subject to a number of risks and uncertainties that may cause our actual results to differ materially including those that are described in our SEC filings. These statements include anticipated plans, timelines of costs and outcomes related to our drug discovery and clinical development programs, and our expectations as to financial items such as cash revenues, expenses, and the repurchase of existing debt.

We encourage you to review our 10-K which was filed on March 11, 2005 and our press release issued earlier today. Paul?

Good morning, everyone. Thanks for joining us. We have made good progress these past few months in all our clinical development programs, but most visibly in our two lead internal programs, the CCR2 antagonist program and the sheddase inhibitor program.

During the year end call in February we covered much of the recent progress with Reverset, our once daily oral nucleoside analogue RTI for treating HIV. At that time we had completed enrollment our Phase IIB study, study 203. This is a six-month double-blind trial comparing three doses of Reverset to placebo in 180 treatment experienced HIV-infected patients. And in that call we described topline results from an interim analysis in the study involved about 140 patients who had been on Reverset for at least four weeks. Those results encouraged us and supported our belief that Reverset could provide sustained clinically significant antiviral activity in treatment experienced HIV patients.

We expect to complete the 16-week efficacy arm of 203 in June which means we should have the final data on these patients in July and assuming that the 16-week data is qualitatively and quantitatively consistent with the interim analysis. We anticipate selecting a dose and proceeding to an end a Phase II meeting with the FDA. And provided the FDA agrees of our plans for Phase III, we anticipate beginning these pivotal trials later this year.

There are a number of ongoing Reverset activities underway related to process development and the commercial scale up of the final formulation of Reverset for Phase III and beyond. This new once daily formulation is prepared as a beadlet capsule as opposed to a coated tablet, which we had been using, and the beadlet capsule has quite significantly but not completely overcome the food effect we saw with the enteric coated tablets.

We are as we mentioned in February also conducting a drug interaction study with ddI, didanosine, to better understand mechanistically why we saw higher-than-expected incidence of asymptomatic hyperlipasemia in patients who were receiving both Reverset and ddI at the time of the interim analysis.

In terms of upcoming announcements for Reverset, many of you probably know we plan to submit a late breaker abstract describing the results from study 203 to the International AIDS meeting and that will take place at the end of July in Rio de Janeiro.

Turning to our CCR2 antagonist program, we recently initiated the first of two one-month double-blind placebo-controlled Phase IIA trials of Incyte 3284, our lead oral compound. This trial is in patients with active rheumatoid arthritis who are also receiving methotrexate and it is primarily a safety and a tolerability study. The goal of the study is to demonstrate that 3284 is well tolerated in rheumatoid arthritis patients who are continuing on their background medications and to facilitate recruitment for our more definitive three-month Phase IIA trial which we expect to begin toward the end of this year.

Although a number of efficacy parameters will be monitored in the one-month study and we certainly hope to see some efficacy trends, I think it is reasonable to assume and I certainly believe that we are more likely to see meaningful efficacy results in the three-month RA trial given the nature for rheumatoid arthritis and the fact that we don't know how long we need to block macrophage recruitment in order to see meaningful clinical outcomes in patients.

The second one-month study, which is on track to begin next month, involves obese subjects who manifest insulin resistance. We are conducting this trial because we saw normalization of insulin sensitivity in insulin resistant diet-induced obese mice when the mice were given an oral CCR2 antagonist. These preclinical results are in line with what is a growing body of evidence that the presence of increased numbers of macrophages in adipose or fat tissue of obese patients and the resulting accumulation of pro inflammatory mediators secreted by these macrophages correlates with the development of insulin resistance.

We believe that the use of a CCR2 antagonist in insulin resistant subjects has the potential to reduce macrophage influx into the adipose tissue, thus improving insulin sensitivity. The results in this study will be the first step in testing whether a CCR2 antagonist can be used to treat diseases such as Type II diabetes and a common related condition called the metabolic syndrome.

In addition to the progress we have made with Incyte 3284, we have identified a number of follow-on compounds from different chemical scaffolds that have demonstrated excellent pharmacokinetic properties and appear to be as selective and at least as potent as 3284. I remain confident that the depth and strength of our CCR2 program will allow us to secure a partner with the resources and the commitment to advance this program in multiple therapeutic indications. And in the meantime, we are prepared and quite capable of advancing 3284 through Phase IIA proof of concept trials and beyond.

Moving to the oral sheddase inhibitor program, we recently began a Phase I trial in healthy volunteers that should give us a clear picture of the pharmacokinetics and safety of Incyte 7839 at various single and multiple doses and allow us to move into formal Phase II testing later this year. As some of you may know, sheddases are members of the ADAM family. These are permealytic (ph) enzymes that have been shown to play a role in controlling the growth and spread of certain cancers that are regulated by the human epidermal (ph) growth factor receptor family. These are receptor tyrosine kinases. And that family is referred to as the HER family (HER).

Several proved drugs that target the HER family including Herceptin, Erbitux and Tarceva, have demonstrated the therapeutic value of blocking these pathways. Unlike these approved therapies, Incyte sheddase inhibitors block the HER pathways at multiple points and in preclinical models these agents have shown efficacy in reducing tumor growth both as single agents and in combination with other agents including both other HER targeted agents as well as cytatoxics (ph). And Incyte 7839 was extremely well tolerated in our preclinical formal toxicology studies.

Lastly we have a number of early stage programs in cancer, diabetes, and HIV that have also progressed during the first quarter. I look forward to describing these to you in greater detail once we have completed preclinical toxicology studies and have selected a lead clinical candidate.

And I will now turn the call over to Dave Hastings to review our financial status.

Thank you, Paul, and good morning everybody. This morning I will briefly review the financial highlights of the first quarter. To begin, our cash position and use of cash are the key metrics we use to measure our financial performance. Our cash used this quarter was in line with our expectations and reflects our commitment to manage the Company in a fiscally responsible and prudent way.

Our ending cash and marketable security balance at March 31, 2005 was approximately 448.7 million. Included in that balance is a $5.7 million reclassification of an investment from other long-term assets into marketable securities. Excluding this reclassification, our use of cash for the quarter was $26.8 billion.

Our use of cash in any given quarter is likely to vary based on the timing of our clinical development expenditures, and we expect our cash use to increase throughout the year as we advance our pipeline. Therefore we still expect to use between 120 and 130 million in cash during 2005. This use of cash is unchanged from our previous guidance.

Our cash guidance excludes any potential use of cash for in-licensings or for the purchase of products or the repurchase of any of our 5.5% notes. As today's press release stated, in April we repurchased and retired $9 million of our 5.5% convertible subordinated notes. With this repurchase, our principal balance remaining on the notes is 119.1 million. As I've said in the past, we will continue to reduce our 5.5% note balance incrementally over time.

Another area I would like to highlight is our revenue, which was 2.9 million. This exceeded our expectations primarily due to timing as well as some additional incremental revenue we recorded in the first quarter. As a result, we have revised our full-year guidance for revenue from 2 to 4 million to 4 to 6 million.

From an operating expense perspective, our first-quarter results were in line with our expectations and therefore our previous guidance for research and development and selling, general and administrative expense remains unchanged. As I said earlier, similar to our use of cash, costs related to research and development are likely to vary from quarter-to-quarter due to the timing of our clinical programs.

Also our results in other income expense were in line and full-year guidance remains unchanged in that area.

In conclusion, our financial performance and careful management and use of cash have put us in a strong position to support and advance our drug discovery and development programs. So with that, I'll turn the call back over to Paul.

Thanks Dave. If we could now open the call please, operator, for the Q&A session.

(OPERATOR INSTRUCTIONS) Thomas Wei, Piper Jaffray.

I wanted to ask about the Phase III trials and one of the recent concerns about the rate of patient enrollment that you are likely to face given the number of other companies with Phase III trials planned for HIV. Can you just help us understand how we should think about that?

Well, we have not finalized our Phase III plans and we certainly are not going to talk about them publicly until we review them with the FDA and get their buy-in. We believe that in the populations that we are considering studying for registration that -- I am assuming in particular you are talking about these large trials for CCR5 antagonists -- that we would be looking at patient populations that at most partially crossed over into the populations that are going to be eligible for the CCR5 studies.

So we are aware of that concern and feel that studies that we are likely to propose to the FDA as well as recognition that we will have to be aggressive in the number of sites that we would bring into the study to mitigate against that concern are the ways that we think we will deal with that issue.

Can you help us understand right now in the current Phase IIB study, what proportion of your sites are also participating in either CCR5 trials or maybe some of the J&J/Tibotec trials?

I don't think we are in a position to help you with that, Thomas.

Maybe one last question before I jump in the queue. You mentioned during your comments that in your formulation work with this beadlet technology you have almost overcome the food restriction. How should we think of that from a practical standpoint and can you give us a sense if you have done any PK work that shows that this does not have the same inter-patient variability with the beadlet technology as has been seen with Videx? Thanks.

The variability is less with this formulation. There is still -- I would say a minor but not insignificant food effect and I still believe that the best way to give the drug especially if it is q.d. is before you eat your first meal. The advantage in that setting of the decrease in a food interaction is that if a patient does fail to eat it on a completely empty meal, the impact on that particular dose would be fairly minimal and that is where we stand at present.

We do have further studies planned to really more fully determine exactly when you could take it regarding meals. But if I had to bet at this point in time, I still would think that we would not want to give it with a meal.

Thanks, that's very helpful.

Eun Yang, Wells Fargo.

I have a couple of questions on Reverset. Paul, you mentioned that in terms of asymptomatic hypoglycemia was higher than you anticipated, the incidence of that. And I'm just wondering whether the incidence is higher than you anticipated or is it higher than the incidence as seen with other NRTIs?

Well, when you combine it with ddI, we have seen incidences that are higher than what you see with ddI alone.

Could you show us what is the difference between the two?

I can't do that at this point because of the blinded nature of the study.

Okay, and the second question is you mentioned that you are planning some late breaker abstract for the International AIDS conference in July. What sort of a data do we expect there and I'm thinking whether we would be able to see 16-week efficacy data?

Yes, you will. The reason we are waiting for the late breaker is so that we can get as much data into that presentation as possible. I actually believe that you probably are going to see pretty much everything that is relevant in July. (multiple speakers)

I was just going to say the one piece of information that might take a little longer is the virology to determine whether we have brought out any Reverset related resistant organisms. That may take a bit longer than July. But I think that clinically the other clinical parameters that we would be and you would be interested I think will pretty much all be available in July in Rio.

When you plan with the FDA at the end of the summer, do you need two additional months of safety and tolerability data or will the 16-week data be sufficient?

We are going 24 weeks. They agreed to talk to us after 16, but they wanted to see the 24-week data. And the way the study was designed, the last eight weeks get us predominately more safety and tolerability data.

Okay and one question on CCR2 inhibitors you mentioned although it is a one-month study, you are monitoring a number of the efficacy parameters. Could you share with us what those are?

In the one-month RA study?

Yes.

We're doing the usual ACR measurements. We're doing some blood work. I think we're doing CRP. I don't remember all of them. They are the usual suspects that you run through for RA, both serologically and clinically.

Now while you are looking at in this (indiscernible) one-month study for RA, is it similar to what Millennium did with their antibody?

I don't think it is. They did these micro biopsies that we are not doing in this study and I think the patient population although they've never -- I don't think they have yet presented it in detail publicly, but my belief is that they used a population that had failed -- they were TNF biologic failures. They were a subpopulation of the whole RA population. And since one of our hypotheses here is that we are a small molecule quasi-mimic of a biological TNF, we certainly want to look at the whole population and not just that smaller 15% or so -- those TNF biologic resistant patients.

So in your study you are including TNF patients who have not been treated with a TNF inhibitor as well as patients who experienced TNF inhibitors?

My belief is -- we're just enrolling but I would be surprised if they are not all on a biologic.

Okay, thank you very much.

Excuse me, let me correct that. I am wrong about that. They are all naive TNF biologics. So I misspoke there.

Adnan Butt, Morgan Stanley.

Most of my questions have been answered but I just wanted to follow up on the trial you mentioned -- you might be conducting with ddI. If you could give us any color on that?

It is a drug interaction study to determine whether or not there is a pharmacokinetic interaction. As you know, if you give Veriad with ddI, you increase the blood levels of ddI.

And when will it be completed by and would you make the results public when it is done?

Say that again please?

When do you expect that study to be concluded? And would you let the results be made public when it is finished?

Yes, we certainly would make the results public and I think the results will be available at Rio when we make the presentation in July.

Okay and then just one quick question for David. About the variability in revenues, any more color on that? I'm just curious as to -- if you continue that trend (ph), then it could become kind of significant for the year. Any more color that you could give?

No. As I mentioned it is variable and I think Q1's revenue really is a reflection of timing for the most part. So we did revise our guidance slightly higher but it is somewhat front-ended this year.

Okay, thank you.

David Witzke, Banc of America Securities.

Good morning. Questions regarding a sheddase inhibitor. First, is it still the case you have not seen rash in animal studies? And can you comment on whether there is any evidence of rash in the early Phase I healthy volunteer study? And I guess in general, your thoughts on the biology of skin rash as it relates to sheddase inhibitor versus the HER 1 antagonist.

We have not seen any rash at high doses one month to species. (inaudible) We are in the single-dose, rising single-dose Phase I and I think we are on the day 9 of our low first multiple dose and we haven't seen any skin rash.

I know that there is a strong belief that the skin rash is mechanism based and I -- we have theories as to why we are not seeing it but we have no experimental data to back up our theories. So to some degree there has is a bit of handwaving here but the theories go -- a theory goes kind of like this. It is our compounds take out ligands that activate the receptors and it may be that in tumors there is an increased density of ligands and specific ligands. And we take out one set more effectively than we take out another that could be part of the dermis.

It may be that we are not as effective in preventing clipping of that particular ligand. It may be also be that you need very little ligand to signal effectively in dermal tissue. In thinking about experiments where you could actually prove or disprove these kinds of hypotheses, it is a little bit dicey and it is a lot of work. So at the moment we are simply pleased that we have not seen the rash and hope that going forward we either don't see it or we see it to a less extent and less severity.

That's helpful and that will be very interesting. Regarding the next steps for sheddase inhibitor, I guess the typical MO for new cancer compound is to take all comers, all tumors and very late stage patients, but given that the pathway is essentially validated by Herceptin and the EGFR inhibitors, would you take a very different route and take the development program to where you have seen success with Herceptin and the EGFR inhibitors?

What we would do in the next -- in the Phase II study that we will start in the fourth quarter is to take patients breast HER plus (ph) and tumors that we know have -- tumor types that have high-density of HER1 receptors, solid tumors.

Thank you.

Annabel Samimy, UBS.

Thanks for taking my call. I just wanted to get a better sense. Are you still looking at the same timeframe for the initiation of the Phase III for Reverset? And I guess what I'm trying to get at is do you specifically need the 24-week data before you initiate the Phase III or can you start looking at that with the 16-week data and design the trial and be able to initiate that before you fully have all the 24-week data?

Yes. That has been the plan that we would go and talk to the FDA with the 16-week data and then we would send them an update with the other eight weeks. I don't think the last eight weeks are really going to influence the study design.

So then the right timeframe should be similar to what you have been anticipating before? (multiple speakers)

Yes, it is an aggressive timeline and I can't say it to the day that that's when we would -- if all things go well we would start the Phase III but that general timeframe is where we still are with the program.

Okay and then on the CCR2 compound, I just wanted to understand. You had mentioned on the call that you are in a position to be able to continue first Phase IIA and beyond. Does that mean that you are considering holding onto it a little bit longer than what you initially had thought in terms of partnering?

We have said all along that if we -- we have continual ongoing discussions with pharmaceutical houses and large biotech companies who have events strong interest at least theoretically, strong interest without writing us a big check at this point in the program. And depending on where we end up in those discussions we either could have a partnership soon or it could -- it may not be soon.

We view this program and actually especially with the disaba (ph) reissue where it is quite easy to contrast the pure anti-inflammatory activity with CCR2 program with the quite obvious immunosuppressant actions of disabary (ph) -- that the program has actually increased in value to -- and we are determined not to do a deal where we don't get full value for the program. So the reason I at every one of these conference calls and when I speak to people in smaller groups, I make the point that since we have a very good cash position, we can take this program quite far and we will until we get the value that we believe we should get for the program.

The only downside to that approach is that we know Merck has a program. We know they are moving along at a reasonably rapid clip. They are maybe six months ahead of us and when they start to go in parallel and look at major disease indications, we are at that point going to have difficulty keeping up with that. So when we get to the later, larger programs, we do need a partner at that point in time. But that is not for example the year 2005, even though I would like to have a deal in 2005, it is not necessary that we do because we can take the program and keep up through let's say parts of Phase IIB.

Okay, great. Thank you.

Alex Hittle, AG Edwards.

I think we have been through most everything I was interested in. Just a couple of quick ones. The revenue I assume is all from the database business? We have not seen any milestones come in?

That is correct, database and IP-related revenues as well.

And by IP, that is -- can you expand on that a little bit?

In-license revenue.

Okay. A second financial question. What determines the pace at which that data is retired?

I think as you know it is callable at par. So I think our strategy is if there are opportunities to retire those notes where it is economically advantageous to the Company, we will do that. And so the open market sort of dictates those terms.

Okay and then finally just a question on the study 203 here. At 14 weeks, who gets unblinded and who remains blinded as you go into the eight week follow-on portion?

24 weeks is when we unblind.

So at 16 weeks though you'll have data that you can take to the agency, so you are unblinded but the investigators and the physicians and the patients are not?

Yes, that's right. What happens at 16 weeks is I think patients -- and I don't want to misspeak here -- I think patients who had been randomized for placebo get rerandomized to either 100 or 200 milligrams of Reverset for the final eight weeks. So that we they are looking at -- we get a little more safety information in the last eight weeks.

Okay, thank you.

Han Li, SunTrust Robinson Humphrey.

Just a quick follow-up on the Phase III Reverset study design. Is it going to be a fixed or multiple dose? Or I assume (indiscernible) in experienced patients in combination with current second-line regimen?

We are anticipating it is going to be one dose. The selected dose and that will be the dose we will go to Phase III with.

Okay and this is going to be for second line?

For what?

For treatment experienced patients.

It will be for treatment experienced patients, yes. What actual patient populations we use for registration studies, we haven't talked about and we won't until we look at the final data and discuss our plans with the FDA. Where we believe the drug has great potential of utility is in the second regiment after you fail first regiment. Whether that is an ideal place to do a registration study is another question.

I see. Another quick question. This is for David. How much of the current '07 are remaining?

119 million.

119. Thank you.

(indiscernible), Susquehanna Financial.

Thank you for taking my question. Most of it has been extensively covered but just a couple of quick follow ups. Without getting into specifics, baseline specifics on study 203, could you just help us, walk us through some of the entry or exclusion criteria in that study?

It's a study where we took all comers, all people who had -- were failing a current regimen and they could be failing their first regimen, they could be failing their fourteenth regimen. I don't know what the -- I think on average they had been on five or six or seven regimens. So there are significantly more experienced people, for example, than the patients that Gilead used in the Veriad studies five years ago. They have seen a lot more agents and they have been on antiretroviral therapy for longer periods of time.

If you had to have a certain amount of virus detectable I think maybe it was 2000 copies per mil or something like that, and then the usual other criteria that you didn't have some horrible lab abnormality that would exclude you from the study. But what we did, we took all comers but we limited any one subgroup of genotype so that we didn't get a skewing of one genotype and not be able to see at the end the study how the drug did in a number of different clinically and commercially relevant genotypes; such as low TAMS, high TAMS, less than three TAMS, great, four or greater TAMS, K65R, M184V, those kinds of things we maximized as a percentage of a given type that could be admitted to the study.

We also -- I think we maximized the number of people who could come into the study who were not able to optimize their therapy after the first two-week period. So we have as it turns out we have about 30% of patients in the study who were treatment experienced enough that their physicians felt that there was nothing to optimize them to after two weeks. So there were 30% of people who did not change their regimens at two weeks and 70% did optimize their regimens at two weeks.

That's very helpful. Then just one follow up on the higher incidence -- you mentioned the higher incidence of hyperlipasemia with ddI. When you did your interim look, did you look at the different dose levels of Reverset and was there sort of a difference in the level of the side effect along the Reverset dose groups through the three Reverset groups?

So you have to remember that when you start to break -- when we looked at 140 patients who had only been on the drug -- had been on the drug for at least four weeks and the time in study was skewed toward the earlier time points, this kind of a side effect occurs out a ways. You usually see it when you see it in the 14- to 18-week timeframe. So when you realize that there could not have been that many subjects with it any way, which makes the statistics not entirely statistically significant at that interim analysis, and then you try to break it down into the dose groups, it becomes kind of a futile exercise.

So I can't give you useful information there anyway even if I wanted to. But the fact that we're still blinded, it makes it awkward to be giving that information out anyway.

Sure I understand. We will just wait for the full dataset. And finally on this new formulation, have you started long-term stability testing with that? And I assume that is what you're going into Phase III with?

Yes, that is the capsule that -- were we to initiate the Phase III studies, it would be with that formulation and we have pretty good stability data on it.

Is there any variability in the -- do you have data regarding some of the metabolites that form? Or the buildup of some potential metabolites?

Well, what you see with Reverset is the only thing you really the see is acid lability of the drug where it turns -- it actually if it is exposed to stomach acid you end up with 5-fluorocydtidine and that can be converted to 5-FU. Remember that was a straw man (ph) early on in the program. You don't ever see any -- but there is no real metabolism of the drug once it gets into the body. It is eliminated from the body in biliary, urinary as the parent compound.

So if you are protecting with the beadlet or with the beadlet more effectively than with the enteric tablet, you should see less of these metabolites. We have not done a lot of work on that but we have done a little, which suggests that that is what you see.

Great, thank you very much for taking time to answer my questions.

Eun Yang, Wells Fargo.

Just wondering how many patients have the ddI Videx included in their regimens in your study currently?

It's about 20, 22, 23%. In that range.

Another question on CCR2. You mentioned that it still remains to be seen how long you have to block macrophage activity to see some clinical benefits. I am just wondering what you have seen in your animal studies and how does that translate into what you might expect in the clinical studies?

So we have an internal friendly dispute about this and it goes kind of like this. In the animal studies, we see pretty good effects with like a week of treatment and we see those effects in the way we have done the two arthritis models, one psychologen induced arthritis model and one is the adjuvant arthritis model. In the adjuvant arthritis model, we have given drug before we give any adjuvant. That is a totally preventive mode and then what we have done is we have waited for disease to begin to manifest itself and in that later and later times, do we began therapy with the rodent-specific CCR2 antagonist, which is 3344. And we see efficacy there too over like a week of therapy.

Additionally, if you look in the diabetes model that we have where we make the animals fat even for 15 weeks on this high-fat diet to where they are frankly diabetic, they have hyperglycemia and hyperinsulinemia and you treat for one week; you normalize, you bring back to control, you normalize completely the glucose tolerance test. So I personally not being a rheumatologist -- and that's pointed out to me frequently here inside the company -- believe that we should see something in shorter term studies.

But the more experienced rheumatologic people in the Company who have actually treated people with rheumatoid arthritis believe that you just can't make that extrapolation. And therefore, you may have to treat a little longer to clear out the actively secreting macrophages in the synovium. So that is why we are making those statements.

And historically most mechanisms that work in rheumatoid arthritis do not do much in a one-month study. You need a three- to six-month study to see what those agents can do. The TNF biologics are an exception in that some patients after a few weeks do quite well. Others do well but it takes -- it still takes longer than the month. So the cautious approach is to say yes, we're going to look but the three-month study is much more likely to give us a definitive answer.

Okay, thanks very much.

(OPERATOR INSTRUCTIONS) At this time, there appear to be no further questions. I'd like to turn the floor back over to management for any closing remarks.

Okay, thanks. Thanks again for your time and we definitely appreciate your interest in Incyte. I think the questions were very probing and very good. In closing, I think we have had a very productive quarter. Our three lead programs are advancing well; various clinical trials, so the second half of '05 promises to be eventful. I guess that is no pun intended but there should be a fair number of events in the second half of this year. And I look forward to keeping you updated on our progress. So thanks again and good morning.

Thank you. And thank you, callers. That does conclude today's conference. You may disconnect your lines at this time and have a wonderful day.