英賽德 (INCY) 2008 Q2 法說會逐字稿

Greetings, ladies and gentlemen, and welcome to the Incyte Corporation's second-quarter 2008 financial results. At this time, all participants are in a listen-only mode and a brief 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, Ms. Pamela Murphy, VP of Investor Relations and Communications. Thank you. Ms. Murphy, you may now begin.

Thank you and good morning. Thanks for joining us. On the call today are Paul Friedman, Incyte's President and Chief Executive Officer; Dave Hastings, our Executive Vice President and Chief Financial Officer. Rich Levy, our Senior VP of Development, is also with us today.

Paul will begin with a brief review of the progress we have made in our clinical programs and Dave will follow with a discussion of Incyte's second-quarter financial results. We will then open up the call for Q&A.

As you may have seen, we issued a separate press release yesterday announcing our intent to offer to sell, subject to market and other conditions, 9 million shares of our common stock. As you can appreciate, this is not something we will be able to discuss during the call today.

Before beginning, I would like to remind you that some of the statements made during the call today, including statements regarding our plans and expectations for our drug discovery and development programs, including timing of our clinical trials and the potential efficacy of our compounds, as well as our expected financial results and financial guidance, are forward-looking statements.

These forward-looking statements are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in our Form 10-Q for the quarter ended June 30, 2008 from time to time in our SEC documents. Paul?

Good morning. As you saw in our press release, the second quarter was highlighted by presentations at scientific meetings on several of our lead compounds, as well as the initiation of additional Phase II trials. (inaudible) at the big meetings provided a full description of our progress with the lead compounds. I'm going to limit my prepared remarks today to very brief reviews at what was presented at those meetings and also list for you up-to-date, ongoing and planned clinical trial activity for our lead programs.

Beginning with Incyte 18424, our lead JAK inhibitor, it continues to demonstrate efficacy in the ongoing Phase II trial in patients with myelofibrosis. Results from the trial were presented at ASCO and also at the European Hematology Association meetings.

In summary, 424 produced unprecedented reductions in splenomegaly, which affects the majority of patients with myelofibrosis and rapidly improved quality-of-life measures, including clinically meaningful reductions in fatigue, night sweats and pruritus. Importantly, it also improved cachexia that is commonly seen in patients with this disease as demonstrated by improved appetite and weight gain. Enrollment of the study is being continued now that we have IRB approval for several amendments that we have put in to continue. We are continuing to confirm an optimal dosing regimen and select the co-primary endpoint for the registration trials.

Later this year, once we have completed these two objectives, we plan to file a special protocol assessment with the FDA. If they agree with the proposed design of the registration trials, we should be able to begin two Phase III trials late this year or more likely early next year. We intend to present the data from the ongoing Phase II study at the ASH meeting in December, the American Society of Hematology.

Based on the efficacy we have seen in the myelofibrosis patients treated with 18424, we have now initiated a Phase II trial in patients with two other myeloproliferative diseases -- polycythemia vera and essential thrombocythemia. Many of these patients share a number of common clinical signs with those patients who have myelofibrosis, including splenomegaly, and the constitutional symptoms associated with what is referred to as the cytokine storm, very high levels of pro-inflammatory cytokine seen in many of these patients. While we expect to have top-line data to share later this year, we believe, at this point, that ASCO may be a more appropriate forum to formally submit and present the PV/ET results.

At EULAR, we presented data on the first cohort of rheumatoid arthritis patients who were treated for a month with 15 milligrams twice a day of 424. The drug was very safe and very well-tolerated. We achieved improvement in all individual parameters of the ACR score with overall responses reaching 50% and 25% for ACR 50 and 70 scores respectively. We have completed enrollment now of the three additional cohorts and expect to present results of the entire study at the American Rheumatology meeting in October.

We have recently completed the three and six-month toxicology studies for 424 and thus, we are prepared to move into a double-blind, placebo-controlled, Phase IIb, three-month trial later this year. This could change if Incyte 28050, the follow-on compound, looks as good as 424 after it completes Phase I. The single-dose arm of the Phase I program is done and thus far, the compound looks very promising.

The multiple dose portion of the trial should be done by September, at which point we can decide if 28050 will become our JAK inhibitor for the oral inflammatory programs. The three and six-month tox studies have already been initiated for 28050, which means we'd be prepared to be given a three-month Phase IIb trial in RA patients in the first half of next year.

Turning to our JAK topical program for psoriasis, we have completed three doses in the subtotal inunction study. Patients in the third dose level applied the topical formulation of 424 on up to 20% of their total body surface area. 424 continues to be well-tolerated and improves quite obviously and dramatically the treated psoriatic lesions. We expect to present data from our topical studies at the European Association for Dermatology and Venereology in September. Based on the safety and efficacy we have seen thus far, the plan is to begin a three-month topical Phase IIb study in psoriatic patients in the fourth quarter with top-line data expected later next year, most likely early in the third quarter.

Turning to diabetes, results from our completed Phase IIa trial with our HSD1 inhibitor, Incyte 13739, were presented at the ADA meeting in June. This 28-day study showed that 13739 significantly improved hepatic insulin sensitivity, decreased plasma LDL and total cholesterol levels. Improvements in peripheral glucose uptake and lowering of blood pressure were also seen.

A 3-month dose-ranging Phase IIb study in patients with type 2 diabetes has been initiated in which once-daily dosing of 13739 is being added to failing metformin therapy. We are looking at five different once-daily doses compared to a placebo arm and expect to involve 300 patients at clinical sites in the US and abroad. The primary endpoint of the trial is the change from baseline to week 12 in hemoglobin A1c and we expect to complete this study in mid '09.

We have completed a single and multiple dose Phase I trial with a structurally distinct HSD1 inhibitor, Incyte 20817. In this study, 817 was well-tolerated and demonstrated appropriate pharmacokinetic and pharmacodynamic properties to support its role as a strong backup molecule to 739.

In our other diabetes program, which targets adipocyte-localized GPCR HM74a to lower pre-fatty acids, we have initiated a 28-day dose-ranging Phase IIa trial with our lead compound, Incyte 19602. Just to remind you, HM74a is a nicotinic acid receptor. The study is expected to involve 120 patients with type 2 diabetes and we expect to have top-line proof-of-concept data from this study early next year.

For our sheddase inhibitor, Incyte 7839, we continue to enroll HER2 positive breast cancer patients in a Phase II trial being carried out in India. The trial is designed to evaluate 7839 in combination with Herceptin with the results expected late this year.

I will now turn the call over to Dave who will provide a brief description of our Phase II financial results.

Thanks, Paul. Good morning, everybody. I will start my brief overview this morning by discussing our cash position. We ended the second quarter with $188 million in cash and investments. So far, our cash use for the year has been $69.3 million. This performance is on plan and our cash use guidance for the year remains unchanged at $132 million to $142 million.

Another area I would like to briefly discuss this morning is our operating expenses, particularly research and development costs. Thus far, operating expenses are in line with our expectations. R&D expense totaled $71.1 million and although our R&D expenses can vary from quarter to quarter due to the timing of our clinical activities, we are on track to incur between $140 million and $148 million for the year. Our R&D spending reflects our commitment to invest in the clinical pipeline, which you saw today, and continues to make excellent progress. So with that, I will turn the call back to Paul.

So let's just move along and open the call for questions at this point, please.

(OPERATOR INSTRUCTIONS). Cory Kasimov, JPMorgan.

Thanks for taking the questions. Two questions here, both relating to the JAK2 program. Could you please discuss the difference, if any, in the burden of proof between the MF indication and PV and ET in terms of most relevant clinical outcomes? And then the second question relates to the developments yesterday, and acknowledging that it's obviously early, but discuss what you learned from the FDA panel meeting for Actemra for the RA indication? Thanks.

So the PV and ET patients that we are enrolling are those who are farther along in their disease and these are people who have the same issues that myelofibrosis patients have, but they still have a hyper-proliferative marrow and with one of the blood cell types predominating in its elevation. With PV, it being the red cell and with ET, it being the platelet.

So what we are hoping to be able to do, and I actually have a reasonable amount of confidence we are going to be able to do this, I know we will shrink the spleens and I know we will improve the constitutional symptoms in the same manner that we have seen with myelofibrosis. That, in its own right, would be of huge benefit to these patients because they suffer from the same kind of debilitating issues that the myelofibrosis patients have.

But beyond that, in these patients, we should be able to take advantage of the myelo-suppressive properties of the JAK2 inhibitory mechanism to bring back to normal or toward normal the elevated counts that these patients have. And that, in a nutshell, is what we are trying to do in this study that we have just started in PV and ET patients, which will involve about 100 patients.

With respect to the Actemra FDA advisory meeting yesterday, we were very, very encouraged by that because it means that both the FDA -- based on the comments that they made and the vote and the discussion that went on amongst the physicians that people are open to these type mechanisms having an important role in systemic inflammatory diseases with RA being one, but there are obviously quite a few others. The really encouraging thing is that when you look at what Actemra does and you look at the PK of the monoclonal antibody, so with something like the eight milligrams that they give, they are taking the interleukin-6 receptor out all day long completely.

Our PK is one where we have a peak of activity and then it falls off and we have off time from the receptor. Additionally, we take out other pro-inflammatory pathways such as the interleukin-12 and interleukin-23 pathways for example. So I think when you couple all of that with where we are in the efficacy that we have seen so far in the rheumatoid patients and with what Pfizer has reported, and we expect them to report in October, I think it augers very positively for oral JAK inhibitors as a breakthrough type of mechanism for systemic inflammatory diseases, obviously including RA.

Great. Thanks for taking the questions.

Thomas Wei, Piper Jaffray.

Thanks. Also two questions here. One is just on the cash that you are raising. Was the plan here to raise enough money to be able to complete the Phase III trials for the myelofibrosis indication? And maybe you could describe where the potential cash position could get you to as far as data readouts go. And then also on the Actemra discussion, are there animal models that predict these side effects with IL-6 inhibition? Would you expect to see a similar side effect profile with 424?

So Thomas, we can't really directly answer your questions regarding the offering. I mean Dave can give you a top-line view of like what he said before, but we can't respond to specific questions on the offering.

Do you want to say anything about it, Dave.

(inaudible) answer Thomas' question on the --

Well, maybe a different way to ask it is have you given us a sense of the cost of the development program for myelofibrosis, the Phase III trial?

No, we haven't given that exact guidance. Although given the number of patients, Thomas, it's not a significant capital-intensive trial.

And that is true across the range of co-primary endpoints that you might involve in the trial?

Yes. It's really driven by the number of patients in the trial, as well as the type of testing those patients require.

And I guess in terms of our cash position, really are guidance hasn't changed at all, Thomas, in terms of the amount of capital required to a potential launch in MF, so there is really no updates there.

So with respect to your question about animal models and interleukin-6, I would say not really with one possible exception and just let me run through what -- first of all, I don't know what the GI perforations mean. There were three, they were in different parts of the GI tract. That could be statistical flu. You do see that sort of thing in rheumatoid patients who are getting steroids or getting NSAIDs. You can see, for example, perforation of duodenal ulcers. I don't know what that means and I am not sure it has anything to do really with blocking the interleukin-6 receptor pathway.

With respect to the lipid increases that were seen, I think that is mechanism-based and I think if you significantly block interleukin-6 pathway, you will see, in some people, increases in their lipid profile.

With respect to the liver, there are multiple mechanisms that were hypothesized for the changes that were seen with Actemra. One of them would be a direct effect in blocking interleukin-6 where interleukin-6 has been shown in animals to be important in liver regeneration in injury models.

So depending on how completely you take out that pathway, you would see, in rodent models, an effect on liver regeneration after different types of injury. Whether or not we would see it, since we have a significant amount of off time during the day, we don't know at this point and we have not investigated that in animal models, but we will going forward.

I will just add one other thing before we go to the next question. It just crossed my mind. I mean so far, Pfizer is looking in a three to six-month study at multiple different doses of their JAK inhibitor and none of those dosing groups have been stopped and we certainly have heard nothing about a significant liver signal. So we may learn more about that at ACR, but I think no news of that type up until this point I think is probably pretty encouraging. And again, may be reflective of the off time that you have with this mechanism during the day.

Katharine Kim, Banc of America securities.

Hi, can you hear me?

Yes.

I have a couple of questions as well. So my question has to do specifically with the timing of the pivotal trials for 424. So will you be able to have agreement with the FDA before ASH so that basically at ASH, we will be able to look at the different endpoints that you have studied? And then right now, as you currently know it, are you fairly certain that the endpoints you are looking at, that you are testing with enrolling additional patients, that you are comfortable that that is going to be one of the endpoints that you are going to have agreement with the FDA?

So what we have done is we have seen in the first few cohorts of patients changes that have guided us to make amendments to the protocol to prospectively, from zero time, do quantitative evaluations of these parameters. So from what we have seen in the first cohorts where the measurements were not done in a prospective quantitative way, because we were trying to see what we would see in the first cohorts, all indications are that all those parameters should show improvement when done in a prospective way now that we have IRB approval for the amendments that are now enrolling in this new cohort. We had to wait -- it takes a while with these IRBs to get approval to move ahead, so we have just begun to move ahead in July.

We have to have more interaction with the FDA, but all indications from the discussions we had with them in the first meeting are that the things that we are looking at are things that they would be receptive to as co-primary endpoints. But we will have to get the results, we will have to show them the results and we will have to get agreement at that point in time.

So when you say am I confident, I am as confident as I can be before we actually get the prospective data and then we will talk to the FDA. I don't think I can be anymore precise than that.

Okay, so there is a possibility then that we might see the data at ASH and you may not have agreement in terms of getting an SPA at that point, that's a possibility?

I think there is that possibility. I think there is a possibility that we won't present all the data at ASH for competitive reasons. We haven't decided that yet. If we had -- if we had -- if we had data that it made sense to present, we would present it at ASH. We may not. We will have to see.

Okay. And then in terms of the RA data, so far, you have enrolled all the patients. Can you make any comments on any safety signals you have seen at the higher doses?

We haven't seen any safety signals. Profoundly safe in this population over one month of treatment.

Okay, thank you very much.

Sapna Srivastava, Morgan Stanley.

It's Dave calling in for Sapna. Just a quick question on the diabetes program. I know that's something you guys have said you would be open to partnering. Have you had any change in the types of discussions that you may be having around this given the perception that diabetes drugs may be more expensive and more risky to develop with some of the things that have been going on at the FDA?

We actually were somewhat relieved after that panel discussion because we were concerned that it was going to be a more onerous discussion then it turned out to be. I think if you don't have -- if you have no CV signal, you should still do pretty well. The size of the trials may be somewhat larger than they otherwise had to be. I think people who play -- big pharma companies that play in this arena are not going to be dissuaded by that. It will probably cost a bit more for them to get from start to finish.

It has not changed the discussions that we are having with people. I mean we have had people who have said they want to wait and see the Phase IIb data. We have had other people who have told us they were very impressed with what we presented at ADA and we have ongoing discussions with those folks. So the tone of those discussions has not changed in any significant way based on everybody learning what happened at that panel discussion.

And have you guys, during either probably I guess during the Phase I part of the development for this program, did you do any measurements of any cardiac parameters like EKGs or QT? I know you measured cholesterol, but any other things that people might want to make sure has been measured before they would step in?

Yes, we certainly have done that. We have done some like -- not Holter monitoring, but where you record heart rates overnight, blood pressure, which actually went down, both systolic and diastolic. The end is small but the numbers look pretty significant. The lipids go down. They don't go up. We don't gain any weight. I mean the mechanism should be a cardioprotective mechanism and I think that is one of the attractive features of the mechanism for people who are in discussion with us.

Great, thank you.

Annabel Samimy, UBS.

Hi, you just answered my question, but just on that same vein regarding the diabetes compound, in the Phase IIb study, are you going to be measuring all of these various cardiovascular parameters on top of the HbA1c?

Sure. We are going to do glucoses, blood pressure, lipids, the whole ball of wax. But the primary endpoint is hemoglobin A1c.

Okay, great. Thank you.

Liisa Bayko, JMP Securities.

Hi, thanks. One question on the diabetes and then one on psoriasis. Can you just talk a little bit about the follow-on compound, how it differs from the first compound for the HSD1? And then just on psoriasis, could you maybe please elaborate a little bit more on what your plans are for Phase IIb in terms of study design?

Say that one again? I didn't hear the second one.

For the Phase IIb for the psoriasis trial for 424, could you just elaborate a little bit more on the study design?

Okay. So for 20817, it is a structurally distinct compound. There is some relation to the lead. It is a more potent compound, but other than that, it is just a structurally distinct backup that has a potency advantage. But it has turned out that, from what we have seen with 739 in man, that it is more than potent enough and it's just the milligram, the daily milligram dose with 817 would be even lower than what you see with 739, but we are anticipating a relatively low milligram daily dose for 739. So at the moment, 817 is not -- we are not planning to take it beyond Phase I, but it is there as a very viable backup for discussions of partnering where the partner would have the confidence that should something happen to 739, you would have a structurally distinct compound as a backup.

With respect to the study design for Phase IIb psoriasis, if Rich Levy is on the line and can address that, I would ask him to do so.

Yes, I am here. So it is a fairly straightforward dose-ranging study looking at three different concentrations of the cream formulation as well as vehicle. So essentially a four-arm study with a fairly large number of patients. I don't think we have said how many yet, but enough to -- more than enough to look at efficacy, which would be quite simple, but also to help be able to distinguish between the concentration and to look further at safety over a three-month period where patients will be treated with the disease up to 20% of their body surface area.

So we have already seen great efficacy in a month. We expect to see greater improvement as you treat for longer than a month. We have seen great safety for a month. We don't believe that there are likely to be significant safety problems for the topical that would come up after a month, but this will answer those questions and then hopefully from this study, you would be able to go on and start your registration study.

Okay, thank you.

Tom Russo, Robert W. Baird.

Good morning, thanks for taking the question. I just wanted to clarify first with 424 and MS, from some of the language in your Q, is there a scenario at all where you would proceed into Phase III without an SPA?

It is conceivable, but I think it would be unwise if -- I mean if we were -- I think it would be unwise not to try very, very hard to get an SPA. So that is our current plan.

Okay. And then with regard to the PV and ET trials, it sounds like there is going to be top-line data before the end of the year. Can you talk about the plans for Phase III there, whether you'd be looking for an SPA as well and whether that potentially could be rolled into maybe one large trial or two large trials maybe concurrently with the MS work?

Well, I would say there may be some data by the end of the year, but I don't think there is going to be that much. I think there will be data on spleen reduction and improvement in constitutional symptoms. But you can take that as a given today that we are going to see improvement in both of those. It doesn't make sense that we wouldn't.

The real key is whether or not we can, in addition to that, lower -- bring down, for example in PV, the elevated hemoglobin. What you want -- while we will have signals, we will have reticulocyte signals and we will probably see movement toward normalization of the red count, the lifespan of a red cell is 120 days. So you are going to have to keep these people and you will have a reasonable number of them on drug for a reasonable period of time to come to whatever the new steady-state is for their red count.

So I think we will have some data by the end of the year. I think it is going to be well into 2009 before we have -- I think we have 100 people that we are planning to put into this study. We are going to have a long enough term data on enough of them to be in a position to finalize plans for pivotals and also whether it would be one or two and exactly how that program would go forward. I think it is a little premature without that data to know precisely what we would do and how soon we could do it.

Okay, and then last question, the diabetes compound, 739, I am just wondering how conservative you are being in terms of data reading out from the IIb study and if it is a three-month endpoint, is there anything that you can do from an enrollment standpoint to kind of accelerate the data from that program?

Yes, so the one thing that we think might help us, but we will have to see whether it actually does, is the fact that there were -- a number of the sites that we are using had patients lined up to go onto studies for the Pfizer inhaled -- the Exubera product, and when those studies fell through, the indication was that they thought that they would have more people available sooner. But the proof is in the pudding there. We are going to have to see whether that does accelerate enrollment. Whether or not -- I think we may be being somewhat conservative, but I would just like to see whether that bears out or the people at those sites have indicated it would. It is early days for that, but there is some hope that we will enroll more quickly.

Okay, and last question, with 424 and MF, have those patients that have continue on now an additional couple of months since the meeting, is there any patients where the durability of effect has been lost while they remained on drug? Thanks a lot.

It is pretty remarkable actually. We have -- we now have three people who have been on drug for more than a year. We have I think 18 who have been on drug for nine months or more. There are a number of those who are approaching a year. It is a durable response. I mean it is pretty remarkable.

Okay, thanks a lot.

Soham Pandya, ThinkEquity.

Great, thanks for taking my question. Most of my questions have been answered, but just one question. Is there any data to show that some of the endpoints that the International Working Group of Scientists recently have any correlation with survival in the MF population? Is there -- I know it is early days, but are there any studies on that front?

So I'm going to ask Rich to address that question. I think the short answer is probably no, but there are some -- but I think there are some parameters that if the patients have those parameters, their life expectancy is less long and since we are affecting them, you might have some degree of confidence, although it is early days, that there could well be a survival benefit. But Rich, can you elaborate on that a bit?

Yes, so there are two ways of looking at survival. One are the characteristics that the patient has when they present to you. So things like severe anemia, increased spleen size, things like that can be measures of poor survival. And so there are a number of survival indices that predict which patients are going to do well and which are not going to do so well. Some have been around for several years. Some are likely to be published, some new ones are likely to be published within the next year.

It is a slightly different question to then ask well, if you improve those parameters with a drug therapy, will you improve survival? The logic of it says yes, but the proof is in the pudding. Now because there have not been any effective drugs in myelofibrosis yet, those things really haven't been tested. So it is known, for example, that if you actually are successful in doing a bone marrow transplant, which has a relatively low success rate in part because of the danger of the procedure itself and is usually elderly patients, if you improve those things, you can improve survival. So we expect, based on the profile of the drug, that several of the attributes of the drug could improve survival, but there is no data out there specifically saying that a drug that does X will improve survival. It's just too soon because we are kind of the first ones to be there and have that chance to see.

That's very helpful. And then just one question on the HSD1 program. Can you just comment on some of the data that you presented in terms of the increase in plasma ACTH levels and then the corresponding sort of downstream effect in the treatment group and then the downstream effect in terms of cortisol coming back. Is that a potency issue or is that a selectivity issue? Can you help us understand that?

Rich, do you want to answer that?

Okay, so the cortisol that is made in the body, a lot of it is made in the adrenal glands. And as was newly appreciated, about a third of it is made in places like fat in the abdomen. So when you use a drug like 13739, which inhibits HSD1, it has no effect on the production of cortisol in the adrenal gland. But it is basically, depending upon the dose, shutting down the production of cortisol and the way it works is it blocks the conversion of cortisone to cortisol in certain tissues, including the visceral fat. So that in the end, the net effect -- initially, the first initial effect is that your total body cortisol is going to go down.

So what happens is the hypothalamus and pituitary sense that there is decreased cortisol. So its normal physiologic function is to put out more ACTH, at least temporarily, to get the adrenal gland to put out more cortisol. So what you see is at least an initial increase in ACTH in some patients to maintain a completely normal cortisol level and not only is it normal when you look at it in the average point in time, but there is also kind of a diurnal rhythm. Cortisol levels are higher in the morning than they are at night. Those rhythms from the adrenal gland are also maintained normally. So this is exactly what you would want to see and it is what we are seeing.

Okay, that's helpful. Thank you.

(OPERATOR INSTRUCTIONS). Rachel McMinn, Cowen and Company.

Thanks very much. I wanted to clarify your comments on the PV and ET enrollment criteria. Are patients in this study, do they need to have splenomegaly in addition to high counts on the red or their platelet cell count?

I believe that's right. That is correct, right, Rich?

Yes, they have to have some degree of splenomegaly, but not the massive splenomegaly that is seen and required in the myelofibrosis study going forward.

Okay, thanks very much. And then just a totally separate question on the metformin. The metformin comment that you made with the Phase IIb 739 study, you mentioned that patients need to be failing metformin. Does that mean that they are going to have to be on maximal doses of metformin or just have an uncontrolled A1c on whatever entering dose they have?

Rich?

Yes, we had considered both of those designs and eventually settled on allowing them to be on whatever dose of metformin that they are on, so that you don't have to titrate them all the way up to the highest dose, which is not tolerated in most people. As a registration -- if this were a registration study, you would most likely have to demonstrate that you could show benefit over the maximum dose of metformin. But it has become the industry standard for Phase II. That is not necessary at this stage to, one, be able to demonstrate that your drug is an effective therapy for a diabetes and two, to help you select a dose.

So at this point, you are just kind of looking for directionally what kind of what level of efficacy you're going to see on top of metformin and then from there, you would do further exploration to look at maximum metformin doses?

Yes. I mean the likely registration study with metformin patients would have to have shown that they couldn't accomplish the same thing by just increasing the dose of metformin. Now obviously, if they couldn't tolerate a higher dose of metformin, you wouldn't have to force the patients to do that. But this is a fairly standard design at this stage and we are very comfortable with it.

Okay, thanks. And then one last question, in terms of the current MF study, I am not sure if you mentioned this before, but can you mention how long you are going to be evaluating patients once you get those additional 50 patients enrolled? Is it just four weeks and then at that point, you will be able to prospectively evaluate these various endpoints?

We will be evaluating them at one month, but we will certainly keep people on the drug just as we are doing now. I hope we will be able to keep many of these people on the drug right up through registration so that we might be able to get some data, some survival data even though it would not be done in a controlled way. We will continue to make measurements of those parameters at intervals beyond a month, but we are hoping that within a month at least some of the parameters will give us what we are looking for.

Okay, so just to be clear then, the one month is what you are hoping will be sufficient to submit to the FDA for an SPA?

We are certainly hoping that, yes.

Okay, thanks very much.

There are no further questions at this time. I would like to hand the floor back over to management for any closing comments.

Well, I appreciate everybody who called in since we changed the day and the time for doing so and we look forward to updating you again at our next quarterly call and with that, I think we will terminate the call. Thanks again. Goodbye.

Ladies and gentlemen, this does conclude today's teleconference. You may disconnect your lines at this time. Thank you for your participation.