BioCryst Pharmaceuticals Inc (BCRX) 2010 Q1 法說會逐字稿

Good day, and welcome to today's BioCryst first quarter 2010 conference call.

Today's call is being recorded.

At this time, for opening remarks and introductions, I'll turn the call over to Mr.

Robert Bennett.

Please go ahead, sir.

Good morning and welcome to BioCryst's first quarter 2010 financial results conference call and corporate update.

Today's press releases are available on our website at www.biocryst.com.

At this time all participants are in a listen-only mode.

Later we will open up the call for questions.

Instructions for Q and A will be provided at that time.

Joining me today on the call are Jon Stonehouse, Chief Executive Officer; Bill Sheridan, our Chief Medical Officer and Stuart Grant, Chief Financial Officer.

Before we begin, I'll read a formal statement regarding risk factors associated with today's call.

Today's conference call will contain forward-looking statements, including statements regarding future results, unaudited forward-looking financial information and Company performance or achievements.

These statements are subject to known and unknown risks and uncertainties, which may cause our actual results, performance or achievements to be materially different from any future results or performance expressed or implied in this presentation.

You should not place undue reliance on forward-looking statements.

For additional information, including important risk factors, please refer to BioCryst documents filed with the SEC, which can be found on our Company website.

Following an overview of Q1 results and developments by Jon Stonehouse and Stuart Grant, Bill Sheridan will discuss the interim results from the first part of BCX4208 Phase IIa study in patients with gout.

Then we'll open up the call for Q and A.

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

Thanks, Rob.

Good morning and thanks for joining us today.

Since our year-end 2009 call on February 4th, we've continued to execute our plan to build an enduring, successful biopharmaceutical company.

Our primary focus remains on transforming our pipeline by advancing our late-stage development programs and by initiating new clinical programs over the next two years.

The positive results announced today from the first part of our BCX4208 gout study represent an important step forward.

In addition, our two IV peramivir Phase III studies in hospitalized patients intended to support U.S.

filing are proceeding as planned.

Assuming flu infection rates return to average levels during the upcoming Southern and Northern Hemisphere season, the two studies should reach their enrollment targets during the first half of 2011.

We are continuing discussions with the FDA and HHS regarding other studies or data analysis that could provide additional evidence of efficacy for the peramivir development program.

In the first quarter we received a final regulatory milestone of $7.0 million from Shionogi associated, with the marketing authorization of peramivir, as well as the first royalty payment from Shionogi for their initial sales of RAPIACTA in Japan of $700,000.

The January launch in Japan coincided with a period of very low flu incidence and this royalty for the quarter reflects the low flu activity.

What's important is that RAPIACTA is now on the market in Japan and we have a strong partner that's well prepared to compete in this important market when flu picks up again and inevitably, it will.

Lastly, we're on track to report top-line data from our four clinical studies during 2010.

These include two BCX4208 gout studies, the ongoing monotherapy dose-ranging study and a combination study of BCX4208 and allopurinol, as well as two forodesine oncology studies, the pivotal CTLC study and the exploratory Phase II CLL study.

We look forward to sharing our results with you later this year.

Now I'd like to turn it over to Stuart to cover our financials.

Thanks, Jon.

Good morning.

I will keep my comments regarding the recent quarter's results and our cash position brief.

From a financial perspective, we are on track to deliver on our cash guidance for the year and that will support the clinical program we're outlining for you today.

Key contributors to the quarter's $26.1 million of revenue include $10.7 million under the HHS development contract for peramivir, the $7 million Shionogi milestone payment Jon mentioned and $6.4 million in collaboration revenues from the sale of peramivir API to Shionogi and Green Cross.

Total revenues in last year's quarter were $4.4 million.

R&D expenses were up due to a second consecutive quarter of high peramivir Phase III development activity and BCX4208 gout trial costs, as well as $6.3 million for the (inaudible) of the peramivir API for our partners in Asia.

G&A expenses were higher, mainly due to consulting fees related to supply chain and process optimization projects.

G&A expenses supporting planned activities are expected to trend down from the Q1 level.

The net loss of $2.6 million compared to $9.3 million in the same quarter last year.

Our use of cash during the first quarter was $4.8 million and our outlook for cash use of between $25 million and $30 million for 2010 remains unchanged.

Now Bill, our Chief Medical Officer, will talk about the BCX4208 gout results.

Thanks, Stuart.

We are pleased to share with you today positive top line results from a planned interim analysis of our ongoing Phase IIa gout study of BCX4208.

BCX4208 is a next-generation, orally administered purine nucleoside phosphorylase, or PNP inhibitor, which has shown a dose-dependent reduction in uric acid levels in the blood in previous studies that had enrolled healthy individuals and patients with psoriasis.

We originally announced plans for this randomized, double blind, placebo-controlled study to evaluate the efficacy and safety of BCX4208 in patients with gout at the end of September.

Part one of the study randomized 60 gout patients with serum uric acid greater than or equal to 8 mg per deciliter (Mg/dl) to either placebo or to one of three doses of BCX4208 administered orally, once daily for 21 days.

Part two of the study is designed to sequentially evaluate the safety and efficacy of up to three higher doses and is now underway.

The BCX4208 dose studied in part one was 40 mg, 80 mg and 120 mg per day.

As part of the screening process, all study subjects completed a 30-day washout period during which they did not receive a urate-lowering therapy.

Additionally, all subjects received gout flare prophylaxis prior to and during the entire period of blinded study drug administration.

The protocol-specified primary end point in this study is the change in serum uric acid concentration from baseline assessed at the day-22 visit.

All three doses of BCX4208 demonstrated a statistically significant reduction in serum uric acid levels compared to placebo, in each case with p-values less than 0.001.

As shown in the table included in today's press release, the median reduction in uric acid concentration ranged from 2.7 Mg/dl for the 40 mg dose, to 3.4 Mg/dl with the 120 mg dose, compared to 0.4 Mg/dl in the placebo group.

We also evaluated the proportion of all subjects in each treatment group who achieved serum uric acid levels below 6 Mg/dl at the day-22 visit, the protocol's defined secondary efficacy end point.

This proportion ranged from 31% for the 120 mg group to 36% for the 80 mg group.

No patients in the placebo group achieved this goal.

In addition, we performed a post hoc subset analysis that included patients whose baseline uric acid levels were less than 10 Mg/dl.

The median baseline serum uric acid level across the study population ranged from 9.2 to 9.7 Mg/dl.

Randomization was not stratified by baseline uric acid level and the number of patients with uric acid levels less than 10 Mg/dl at baseline therefore varied from 8 to 13 in each group.

The total of 41 of 60 subjects, or 68%, had a baseline uric acid level below 10 Mg/dl.

For these 41 patients, the proportion who reached uric acid levels less than 6 Mg/dl ranged from 30% to 63% in the different BCX4208 dose groups.

Again, none of the patients in the placebo group achieved this goal.

We evaluated safety with regular clinical and laboratory examinations, including blood chemistry and hematology, including lymphocyte counts in all patients.

BCX4208 was generally safe and well-tolerated at the doses and duration evaluated in this study.

All 60 subjects completed the study.

Overall, the frequency of adverse events in each of the BCX4208 treatment groups was comparable to that observed in the placebo group.

The incidence of gout flares observed was low in all study groups.

Reductions in peripheral blood lymphocytes were observed in patients treated with BCX4208.

The study protocol included stopping rules for study drug administration when CD4-positive cell counts fell below certain thresholds.

No subjects were discontinued due to low CD4-positive cell counts.

Additional studies designed to evaluate longer-term exposure are needed to further define the safety and tolerability profile of BCX4208.

In summary, we are pleased with these interim findings which support continued development of BCX4208 in gout subjects.

We have and will work with our investigators to submit the findings for presentation at an upcoming scientific meeting and have initiated part two of the study and intend to announce top line results when that phase is completed.

The encouraging efficacy and safety findings of this study also support proceeding with an additional trial to evaluate BCX4208 as monotherapy, and in combination with allopurinol, to determine if inhibition of xanthine oxidase and PNP has an additive affect in reducing uric acid in gout patients.

We intend to share top line data from this combination study in the fourth quarter this year.

Together, these two studies should define dosing suitable for longer-term exposure studies of BCX4208 in patients with gout.

We look forward to providing you with further updates as new data become available.

Thanks, Bill.

The execution of our 2010 clinical plan is off to a good start.

In addition to delivering these promising interim results from our first gout study, we've completed the enrollment in our two forodesine oncology studies.

For the remainder of 2010, we expect to complete the ongoing gout study in the coming months and to report top line data from the combination study of BCX4208 and allopurinol in the fourth quarter.

In oncology we plan to report data from the pivotal study of forodesine in patients with cutaneous T-cell lymphoma and the exploratory Phase II study of forodesine in patients with CLL in the second half of this year.

With that, we'll open it up to questions.

Thank you.

(Operator Instructions) Charles Duncan, JMP Securities

Hi guys, thanks for taking my questions and congratulations on a good quarter of progress.

Thank you, Charles.

My first questions are on 4208.

First of all, Bill, I'm wondering if you could give us a little bit more color on the changes in white blood cell counts.

Basically, what was the stopping rule?

Hi Charles.

So the stopping rule had two components; one based on total lymphocyte count falling below 500; the other one based on CD4-positive cell counts falling below 350 and the rule was to confirm that that observation was correct with a repeat test.

And if confirmed, then the patient was to be removed from study drug administration.

And you did disclose that you saw some changes but none of the patients reached the stopping rule.

I guess my question is with the next steps moving up in dose, do you think that you've got enough headroom to be able to see some efficacy at the higher doses with these stopping rules?

So, yes, I think that it is a stepwise approach.

So we're very comfortable in moving up to the next dose planned in the study, so that's been initiated and after each sequential cohort we'll take a look at the data and make a decision based on the safety.

We've already proven efficacy in Part A of the study and we'll see, in due course, whether additional dosing with higher doses will result in higher rates of a fall of uric acid and a greater proportion of patients achieving goal.

So we certainly think that's worth doing and, absolutely, we think it's worth doing a combination therapy study to fill out the program.

And just to further comment on the lymphocytes, clearly because of the mechanism of action this is an anticipated pharmacologic effect of this class agents and it's an immunomodulatory effect.

We don't know whether that's going to be potentially beneficial in gout patients either, so we need to keep that in the back of our minds.

I was going to say it looks like you've got pretty competitive efficacy at the lower doses.

What's your thought about the interaction with, say, allopurinol?

Do you think that there is potential for a synergistic affect or an additive affect, given the differences in mechanism?

So allopurinol works on a xanthine oxidase enzyme and BCX4208 works on a different enzyme, purine nucleoside phosphorylase.

They're both in the pathway of purine nucleoside degradation that ultimately results in uric acid.

So it's an experiment that's definitely worth conducting.

And we can't do that particular experiment in animals because animals don't make uric acid, they destroy it with another enzyme.

But the clinical experiment is required and it's definitely worth doing and we believe there's potential to see an additive or synergistic effect.

Excellent.

Now, could you also kind of review with us for in terms of 4208 the discovery platform?

Do you think that there are some additional compounds that could come out of or off the shelf out of your platform?

Yes.

I think one of the things, hopefully, investors are starting to see with BioCryst is we're much more than a flu company and the evidence of another molecule, BCX4208, hitting the efficacy end points we were hoping for is an exciting step forward.

But we're a platform Company of structure-based drug design and there are a number of additional molecules that we're currently reviewing and hope to bring forward and give you an update on that this summer.

Thanks, Jon.

I'll hop back in the queue.

Thanks for the added color.

Bret Holley, Oppenheimer; Analyst

Yes, thanks for taking my questions.

I was wondering, just temporally within the 21 days, whether there was, I guess, a plateau in the lymphocyte reductions or did you get kind of a continual reduction.

Can you give us a little bit of information on that?

Sure.

Thanks for the question.

The action on uric acid is quite prompt and in this study we had evaluations at baseline, 24 hours after the first study drug administration, and also weekly.

And you do appear to have a plateau as early as one week after the initiation of therapy with BCX4208 and even at day two values do show a difference compared to baseline.

So we don't need long-term studies to confirm efficacy here.

We need long-term studies to more fully evaluate the safety and tolerability profile and the action in combination with other drugs and as the program unfolds, demonstrating efficacy is not going to be a problem.

Yes.

I guess my question was more along the lymphocyte reductions and whether you actually saw a plateau in the reductions there and/or in some kind of rebound in those lymphocyte counts over the 21-day period.

So three weeks is too short, probably, to see a full effect on lymphocytes and we need longer-term studies to fully evaluate that.

There are different lymphocyte compartments and there are quite long-lived cells and they circulate back and forth between the tissues and the blood.

So in our previous psoriasis study, it's possible we may have seen a plateau in six weeks, but in future studies we plan longer-term administration of the order of three-to-six-months and we'll make decisions about that as we see the data from the current program unfold.

Okay, and did you actually see any infections on the drug arm in the trial?

No.

Several subjects had viral upper respiratory tract infections or head colds, in other words, and the rate of that was no different comparing placebo and BCX4208-treated subjects.

Great.

Thank you very much.

Steve Byrne, Merrill Lynch

Hi, Bill.

I have another one for you.

If you were to segment the patients based on degree of renal impairment, did you see any differences between the treatment arms and/or tolerance or safety signals?

So the eligibility criteria for the study, Steve, included a creatinine clearance criterion based on the serum creatinine.

So subjects were eligible or patients were eligible if they had a renal function that was at least 50% of normal.

We have not done the analysis you were just suggesting.

That will be something we'll do when we finish the study and have the full data to hand across all the cohorts.

But we don't anticipate any issue with renal function from a safety perspective, with this class of agent, on the basis of our experience with forodesine and BCX4208.

BCX4208 is partly cleared by renal excretion and as the program becomes more mature we'll define the dosing required, if necessary, to adjust in renal impaired patients.

It may or may not be necessary.

We'll define that as the program matures.

Okay and with respect to the lymphocyte reduction, was there a dose response relationship that differed materially from the dose response relationship you saw with the serum urate reduction?

I think, broadly, the lymphocyte count reductions are similar across the different BCX4208 arms.

It's also worth emphasizing that it's a different type of an assay and the natural variability in lymphocytes in the blood is much, much, much greater than the natural variability of uric acid from day to day.

So, as we accumulate more patients and test the higher doses, we'll take a look at the -- if there is, in fact, any relationship between dosing and the lymphocyte effect when we've got all of the data to hand.

But right now, it looks pretty flat.

And I have just one more for Stuart.

The $300,000 of product sales, was that just a remnant of the U.S.

government order in the fourth quarter or were you actually picking up a new customer here?

That was not U.S.

government.

It was just small orders from a variety of different countries.

Okay.

Thank you.

Bill Slattery, Deerfield.

Hey, thanks very much, guys, and continued congratulations on the progress.

Two questions, first on peramivir.

Your language is a little bit on the cautious side.

You used the term "assuming" and "should." In the event that the assumptions play out falsely and the study is unable to read out in the time frame that you described, do you we just simply push it back into the U.S.

hemisphere for the following flu season?

Or how do we think about when the data is most likely to be reportable?

No.

I think that when studying these acute seasonal infectious diseases you're totally reliant on the disease cooperating and we can't predict, with any degree of accuracy, the scope of the flu season.

So you base your planning assumptions on averages and just as long as we get average flu seasons we should be fine with the timeline we suggested.

Obviously, if we have big pandemics or epidemics or a big seasonal flu, we might be able to finish a bit earlier.

But honestly, I think we're going to need the full three seasons; if the flu is not up to expectations, then that will have an impact.

(multiple speakers) The impact, though would not be to undermine the result.

It just would be simply to push it out?

Yes.

This is Jon.

And we just continue to follow flu around the globe.

Okay.

So if it didn't finish in the Northern Hemisphere we'd go to the Southern and our strategy remains that we want to file sometime in the end of 2011 or early part of 2012, so that, come the 2012 flu season, we have a drug approved and on the market, assuming that the trial results are positive and the FDA approves.

So that's our strategy and we're just trying to be realistic.

We've done enough of these studies now to know there are bumper crop seasons for flu and lighter flu seasons and we just want to be realistic about the incidence of flu and how it affects our trial.

No and that absolutely makes sense and I appreciate the clarification.

Now, quickly on 4208, understanding the PNP biology and its effect on CD4-postive versus CD8, CD20, CD56, is there a particular lineage that is more susceptible to an early effect that can give you a signal as to whether or not there's going to be a more profound level of downstream affect on B and T-cells?

Or are they all fairly uniform in terms of their responsiveness to therapy and their responsiveness to the production side rather than the consumption side of B- and T-cells?

Okay.

So, in this program we're measuring CD4, CD8, CD20 and CD56-positive cell (multiple speakers) uptick.

It's a bit premature to come to conclusions about whether one or other subset is more affected and so I'd like to see the full study results before interpreting the data.

And as I mentioned before, there's quite a lot day to day variability in these counts, even in normal people who don't have anything else going on.

With regard to what's important, I think two things are important in thinking about the lymphocyte count.

One is, what are the clinical consequences that might be adverse with regard to a mild or moderate suppression of lymphocyte counts?

And the only way to answer that question is to do large studies and so that's really a Phase III question.

The second thing that's important is whether or not this immunomodulatory effect of the drug might actually be beneficial in people with an inflammatory disease like gout and that's one of the reasons we wanted to study BCX4208 in this population.

And there are cytokines made by inflammatory cells, stimulated by lymphocytes in these types of diseases.

There's no way of looking at that, really, in an informative way in the labs, so that's something we'll pay attention to in terms of the incidence of gout flares and the like in our study.

Okay.

Hey, can you just remind us of when we're likely to have this information presented in a peer-reviewed setting?

So we haven't made a final decision as to where to submit it.

Obviously it's too late for EULAR though, so you can count that out.

The deadline for abstracts there was in March.

And there are other opportunities later in the year, like ACR and others, and we'll work with our top investigators to get the abstract written and submitted to appropriate places.

Thanks very much for taking all my questions.

Steve Harr, Morgan Stanley & Co.

One follow up to some of the questions that have been going along here.

So the drug, as you've said, is renally excreted.

Clearly gout patients have mixed renal functions.

Can you help us understand, from what you've seen to date, how variable CD4 counts are within a dose?

So how much risk do you have as you go into a more real world population that you're going to take patients into a zone where maybe you and physicians and regulators are comfortable?

So just a slight correction first.

The drug is partly renally excreted, so as the program matures we'll define the appropriate dosing in subjects with renal impairment and the creatinine is a common standard biochem panel test and you get that on essentially all these patients.

So it's not an additional burden for the healthcare system or the provider or the patient to understand what is their renal function before they embark on a new therapy.

That's part of normal medical practice and an appropriate dose can be selected based on the pharmacology program that will accompany the development of the drug.

So I'm quite confident we'll be able to work that out.

So the dosing might or might not have to be amended, but it'll be straightforward.

The second part here is to do with the variability of CD4 and will we need to pay attention to that once the drug's on the market.

I think that's an interesting question that we'll be able to answer during the Phase III program.

And for example, if the Phase III program turns out to be a combination therapy or add-on type of a program, the dose of BCX4208 required might be low.

And the probability or the risk of having a CD4 count persistently low, we'll obviously be defining that in these large studies and whether or not that's important remains to be seen.

So I think that these questions are good, but they're not answerable in full at this stage of the development program.

I'm sorry.

I wasn't trying to get in the post-marketing [setting], and I think this is answerable question.

How much variability are you seeing?

I want to understand if you go from 40 mg to 80 mg to 120 mg, do we have a direct --

No.

-- understanding of what the CD4 count will do?

And then how close how are you to -- I mean, 350 isn't exactly the -- I think it obviously be more comfortable on higher.

But are you getting close to that, even within some patients with that dose and is there a clear dose response on CD4 counts to date?

In this dose range there is not a clear dose response in any of the lymphocyte subsets.

I think that the sample size and the natural variability may be obscure.

There might be one.

So we need more data, but in what we can see so far the answer to the question is no.

Are we getting close?

The baseline CD4 varies a lot over a huge range.

So people who start off with a relatively lower CD4 might be at more chance of falling below a certain threshold value than people who start off with a higher one.

So we're bound to see subjects, as we escalate the dose.

Let's be crystal clear.

We're bound to see people fall below 350 and so the question is how often does that happen, what are the baseline factors that have associated with that.

You've alluded to one potential factor.

And we'll look at all of those questions.

I think another important thing and maybe this didn't come up strongly enough in the prior comments is to see the full effect on lymphocytes you need longer-term administration of the drug.

So I think I would caution against extrapolating three-week data to be the final conclusion for anything on lymphocytes and we'll do those longer-term studies.

Ren Benjamin; Rodman.

Hi, good morning, guys and thanks for taking the question and congratulations on the results.

Can you just give us an idea as to what the therapeutic landscape looks like, just in broad brush strokes?

Is it a pretty crowded field?

Would you have to go after, let's say niche type of patients?

How would 4208 sort of differentiate itself from other products that are out there?

In talking with the experts who advise us, our sense of the field right now is that it's still pretty much allopurinol first line therapy.

That drug has been around for many decades.

It's well understood.

Most people are pretty comfortable with using it.

And then there's a group of patients that might be quite large, actually, who don't achieve the therapeutic goal with allopurinol.

Some of those patients visit rheumatology offices if they're difficult to manage and our sense is it's pretty difficult to compete against a cheap generic for first line therapy.

And second line therapy, either as an add-on or a combination or a monotherapy, I think all of that's still open with BCX4208 is where we're thinking about the landscape.

I think it's great to see advances in the field here and there obviously -- there's a new drug that's been introduced to the market that's another xanthine oxidase inhibitor.

There's pegloticase that's been under development.

So the field is moving forward after several decades of stagnation.

Yes and one of the things that I think we're encouraged by is seeing a big company like Takeda really start to advocate early treatment and going after the primary care physicians, because that's something a little company like BioCryst can't generate.

So, hopefully, we'll see more people getting treatment in a timely fashion as a result of that.

And as Bill says, I think there's still a lot of room for new drugs to come forward and certainly the speed at which we get these trials enrolled and the enthusiasm that investigators have shown is an indicator of that.

Can you talk a little bit about the longest the preclinical tox studies have been carried out and would you need to go longer, and potentially, what's the longest dosing that patients would need to be -- time frame patients would need to be evaluated?

So the nonclinical safety program, if a drug development keeps going, when you're in clinical development doesn't stop when you file the IND, obviously.

And so, obviously, the studies we have currently are well supported by a nonclinical safety program and we intend to get into six-month human studies.

Certainly that'll be possible next year.

So the six-month animal toxicity studies are just ongoing or have they been completed or are they about to start?

They're maturing and we'll have all of the answers to support a six-month clinical program in 2011.

Okay, terrific.

Thank you very much.

Joseph Schwartz, Leerink Swann.

Hi, thanks.

I was wondering if you had any reasons to think that the dose response curve is not linear and you're on the low part of an S-shaped curve or something?

Why go higher in dose with a lack of a dose response that's been seen so far, if there is the theoretical concern about of infections at some point?

So this is a fairly -- this is not a Phase III study.

This is a Phase II study and in Phase II development one of the objectives is to delineate over a fairly broad range dose response effects, both on efficacy and safety issues.

We are very comfortable with short-term administration in doing that and that'll help to bracket the doses that we eventually pick for full development and will support the ultimate NDA and overseas applications and justify choices of doses in Phase III and for commercialization.

So it remains to be seen whether those higher doses are suitable for full development or not.

Maybe they will, maybe they won't, but it's important, at this stage of development, to bracket the doses that you might want to use in the future.

Okay and can you remind us of the half life in the event that you do see any adverse events or infections, the ability to stop and reverse whatever it is and then how is it metabolized and what is the kinetics like upon repeat dosing?

So let's start with your last question first.

You reach steady state within a fairly short time and in thinking about what happens when you stop dosing, I'd say two things.

One is that the drug is going to be cleared from the system relatively quickly.

The half life supports once a day dosing without any problem and so the drug will get cleared from the system relatively quickly.

Lymphocytes are a special cell set in the body and they have -- they're made in the bone marrow in the thymus gland and they're also -- you can ramp up the lymphocyte production in response to an infection extremely quickly in lymph nodes and so on.

So the turnover of that compartment is what's going to determine how quickly lymphocytes recover.

So, for example, I'm sure you're familiar with rituximab, Rituxan, for B-cell malignancies, a Genentech drug.

And if you use Rituxan, you really wipe out B-cells and once you stop the drug it takes months for the B-cell compartment to recover.

It's not because the drug's still there.

It's just because it takes months for that compartment to recover.

So the effect of PNP inhibitors on lymphocyte compartments is nowhere near as strong as wiping out B-cells, but it's still true that it takes, in different compartments of lymphocytes, it's all dependent on how quickly that lymphocyte compartment recovers once you remove the agent from the body.

It's got nothing to do with the drug half life anymore.

Okay, that's helpful and I know Roche had this drug for a long time.

What did they learn about drug interactions and the ability to combine with a drug like allopurinol?

I'm not sure which drug you're referring to.

4208.

4208?

Yes, still just 4208?

They didn't study it in gout at all, so they didn't -- there was no program to develop the drug in gout.

There were no interactions studies with allopurinol.

Yes, but the one thing I would say that we got from Roche was a pretty robust preclinical package and a lot of detail work that they did in studying the drug prior to the psoriasis studies that they started.

Okay and the metabolism?

Is it complementary?

Or is it competitive in any way with allopurinol?

No.

We don't anticipate any drug-drug interactions based on the pharmacology or the (inaudible).

Okay, great.

Thanks so much.

Michael Murphy, New World Investors.

Thanks.

I have a couple questions about peramivir, but first I just wondered what the follow up is on the missing earnings estimate.

I know you talked at first call in early March and it's been almost two months since that estimate went missing and I wondered what their explanation is.

Sorry, can we get that question again?

Yes.

The missing earnings estimate?

I know in early March you talked your first call about why the high estimate went missing and it still hasn't appeared again and I wondered what their explanation for that is?

I never really -- I mean, there is no explanation that we have, but there has been active follow up on that.

Okay.

On peramivir you said your discussion with the FDA other data analysis that could support the filing.

Does that include analyzing the results from EUA usage?

Yes.

There's a broad range of possibilities here.

That might be one of them, but I think that EUA is a very specific event under the PREP Act.

We don't have any direct access to those data, so there are other trials under consideration and those discussions are ongoing, so it'd be premature to get into the details.

Okay.

I was glad to see you have the systems in place to book the Shionogi royalties in the same quarter that they book the sales rather than after a one-quarter delay and I wondered if you can give us more detail on the break points on the royalty schedule?

Or when you might be able to do that?

So we think that, yes, it was encouraging for me as well to see we had the processes between Shionogi and our sales to be able to do that and the way the contract is structured, we feel confident that we should book that revenue without any risk of future adjustments.

We've given publicly, under the contract, between 10% and 20%.

We haven't broken that out, Michael, I'm sorry.

No that's okay and the Southern Hemisphere flu season, can you just quickly review which countries appear likely to use peramivir or have committed to it and if you can, comment on any prospective countries that are in the evaluation process?

So the way we can describe it is there's a set of countries that we're working with for the clinical studies and then through our partners we've got relationships around stockpiling and the like.

I would say we've been in conversations on our own for Australia.

We've been -- our partner, moksha8 has been in conversations with Brazil.

And then there's a whole list of countries that we're working with in terms of a clinical study.

Australia, New Zealand, South African and some South American countries.

Great.

My final question, you might not be able to do this.

But I wondered if you could comment on the 4208 results compared to Ardea's gout results that were released at the end of March?

Sure.

We can make a couple of comments.

I think the studies are different and you always need a buyer beware signal before comparing different studies.

There are a few differences in the design.

Their study excluded patients who were over-producers of uric acid.

It was restricted to under-excreted; we had no such exclusion criterion.

Their study was a dose titration experiment; ours is not.

Ours is a parallel group randomization with no dose titration in individual subjects.

So, broadly speaking, I think that the range of uric acid reductions are similar, would be the comment I would make, but you need to be aware of the differences in design between the studies.

Great.

Thank you very much.

Joseph Schwartz, Leerink Swann.

Hi, thanks.

You just answered my question about the royalty rates for peramivir, but I was wondering if you'd just give us a sense of the pricing and where that stands in Japan?

Yes.

So the pricing is about double what Tamiflu is in Japan, so it's around $65 U.S.

for a single course of 300 mg and so we think -- remember that the Japanese government sets pricing in Japan.

So the fact that they got a floppy premium over existing therapies in the market is a pretty good sign.

And as I said in my prepared comments, the real key is when flu is back, which we know it will come back.

We're confident that Shionogi is the right partner and prepared to compete effectively with RAPIACTA.

Okay, great.

Thanks.

(Operator Instructions) And sir, I'm showing no questions in the queue.

So I'll go ahead and wrap up if there aren't any more questions.

So, again, we want thank everybody for your participation today and just remind everybody that our goal at BioCryst is to build an enduring, successful, biopharmaceutical company and I think the progress we've made in the first quarter and the results of our first BCX4208 study in gout are a very nice step forward towards that goal.

So thank you for your interest in BioCryst and we'll keep you updated as the year progresses.

Ladies and gentlemen, thank you for your participation in today's conference.

This concludes the program.

You may all disconnect.

Everyone have a great day.