BioMarin Pharmaceutical's CEO Discusses Q3 2011 Results - Earnings Call Transcript

| About: BioMarin Pharmaceutical (BMRN)

BioMarin Pharmaceutical (NASDAQ:BMRN)

Q3 2011 Earnings Call

October 27, 2011 5:00 pm ET

Executives

Stephen Aselage - Chief Business Officer and Executive Vice President

Henry Fuchs - Chief Medical Officer and Executive Vice President

Jean-Jacques Bienaimé - Chief Executive Officer and Director

Eugenia Shen - Senior Manager of IR

Jeffrey H. Cooper - Chief Financial Officer and Senior Vice President

Analysts

Nicholas Bishop

Eun K. Yang - Jefferies & Company, Inc., Research Division

Liana Moussatos - Wedbush Securities Inc., Research Division

Cory William Kasimov - JP Morgan Chase & Co, Research Division

Christopher J. Raymond - Robert W. Baird & Co. Incorporated, Research Division

Navdeep Singh - Deutsche Bank AG, Research Division

Laura A. Ekas - Collins Stewart LLC, Research Division

Shin Kang - Wells Fargo Securities, LLC, Research Division

Tim Lugo - William Blair & Company L.L.C., Research Division

Alan Leong - Biotech Stock Research

Joseph P. Schwartz - Leerink Swann LLC, Research Division

Operator

Good day, ladies and gentlemen, and welcome to the Third Quarter 2011 BioMarin Pharmaceutical Inc. Earnings Conference Call. My name is Jennifer, and I will be your coordinator for today. [Operator Instructions] As a reminder, this conference is being recorded for replay purposes. I now would like to turn the presentation over to your host for today's conference, Ms. Eugenia Shen, Investor Relations of the BioMarin. Please proceed.

Eugenia Shen

Thank you. On the call today is J.J. Bienaimé, BioMarin's Chief Executive Officer; Jeff Cooper, Chief Financial Officer; Hank Fuchs, Chief Medical Officer; and Steve Aselage, Chief Business Officer.

This nonconfidential presentation contains forward-looking statements about the business prospects of BioMarin Pharmaceutical, including expectations regarding BioMarin's financial performance, commercial products and potential future products in different areas of therapeutic research and development. Results may differ materially depending on the progress of BioMarin's product program, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market and developments by competitors and those factors detailed in BioMarin's filings with Securities and Exchange Commission, such as 10-Q, 10-K and 8-K reports. And now I'd like to turn the call over to J.J., BioMarin's CEO.

Jean-Jacques Bienaimé

Thank you, Eugenia. Good afternoon, and thank you for joining us on today's call. As usual, a few introductory comments before Jeff reviews the financials for the third quarter of this year, and Steve provides more details on the commercial activities, and then Hank will provide an update on a few of our ongoing R&D programs before we open the call for questions.

So we are pleased with the progress we have made so far this year. Starting with our commercial portfolio in the third quarter of 2011, there was a year-over-year increase in BioMarin's net product revenues of 17% to $113 million. Our cash balance was $370 million at the end of the quarter, down from $412 million at the end of the second quarter. The primary reason for the decline was the $48.5 million spent on our new manufacturing facility in Ireland, which was completed during the [ph] third quarter.

Excluding these, our cash balance increased quarter-over-quarter. As for our clinical and preclinical programs, we have made important progress on advancing our pipeline. We have several major clinical milestones expected in the next year or so, including results for the Phase II trial for PEG-PAL, the pivotal Phase III trial for GALNS, the Phase I/II trial for BMN-701 for Pompe, the Phase I/II trial for BMN-673 for genetically defined cancers and the neurocognitive trial for Kuvan. The positive outcome in one of these trials or more of these trials could have significant implications for the future of the company. And with this in mind, the successful execution of our pipeline is a top priority for the company and we plan to host an R&D day in New York on December 8 to discuss our pipeline progress in more details.

Moving on to the investigator-sponsored trial of Kuvan in autism. The data from this small single-center Phase II study was presented in a poster presentation at the American Academy of Child and Adolescent Psychology on October 20. The study did not need its primary or secondary endpoints. However, 3 subscale secondary measurements, we did [ph] it to social awareness, autism mannerisms and language with statistical significance. Since the open-labeled portion of the trial is ongoing, it is premature right now to speculate on additional study outcomes or any next potential steps for BioMarin. We do not believe that the results from the autism trial will be predictive of our ongoing neurocognitive study for Kuvan in PKU, as it is likely that the mechanism of actions defers in this 2 indications. Kuvan's ability to lower Phe levels in some patients and the correlation between high Phe levels and the neurocognitive deficits in PKU patients has been well documented through different meta-analyses, and whereas the cause of autism is still unknown.

And in terms of guidance, we have made a few adjustments. We increased the bottom end of our Kuvan expectations from a range of $112 million to $120 million to a range of $115 million to $120 million. We also raised our expectations for R&D spend from a range of $200 million to $205 million to a range of $205 million to $210 million. The higher spend is attributable to our increased efforts for the successful execution of our pipeline programs, which resulted in better-than-anticipated enrollments in our clinical studies. Our new non-GAAP adjusted EBITDA is in the range of $45 million to $55 million. Now I would like to turn the call over to Jeff Cooper, who will review the financial results for the third quarter of 2011.

Jeffrey H. Cooper

Thanks, J.J. I will start by reviewing product revenues for the third quarter of 2011, and then follow with a more in-depth look at our operating expenses and financial results. Beginning with Naglazyme, net product revenue was $55.9 million for the third quarter of 2011, an increase of 8.1% as compared to $51.7 million in the third quarter of 2010. Changes in foreign currency rates net of hedges had a negative $0.5 million impact in the third quarter of 2011.

Net sales of Aldurazyme by Genzyme were $46.3 million for the third quarter of 2011, an increase of 13.5% as compared to net sales of $40.8 million in the third quarter of 2010. Foreign currency exchange rates caused an increase to total Aldurazyme sales of $2 million in third quarter of 2011. Net product revenue of BioMarin-related Aldurazyme was $23 million for the third quarter of 2011 compared to net product revenue to BioMarin of $16.5 million for the third quarter of 2010. During the third quarter of 2011, there was a positive $4 million impact from inventory transfer revenue compared to immaterial impact from the third quarter of 2010. Net product revenue for Kuvan of $30.5 million for the third quarter of 2011 increased 16.4% as compared to $26.2 million in the third quarter of 2010. Finally, net product revenue for Firdapse was $3.5 million for the third quarter of 2011 as compared to $2.2 million in the third quarter of 2010.

Now I'll review gross margins, operating expenses and other items in more detail. For the 3 months ended September 30, 2011, gross margins for Naglazyme were 83%, Aldurazyme gross margin were 68%, Kuvan gross margin were 83%, and finally, gross margin for Firdapse were also 83%. Research and development expenses increased by $19.2 million to $58.6 million in the third quarter of 2011 from $39.4 million in the third quarter of 2010. The higher costs in the quarter were driven by increased clinical cost for the GALNS Phase III trial, the PEG-PAL Phase II trial, the PKU-016 and the neurocognitive study for Kuvan, the Phase I/II trial for BMN-701 and preclinical development of BMN-111. We do not expect cost for these development programs to recur at the same levels in the fourth quarter 2011 due to the timing of clinical material purchases and certain costs associated with preclinical activities that occurred in the third quarter.

Selling, general and administrative expenses increased by $6.5 million to $44.9 million in the third quarter of 2011 from $38.3 million in the third quarter of 2010. Major drivers for the SG&A increase include -- during the third quarter of 2011 are increased corporate expenditure including IT, legal, administration and foreign exchange as well as increased Naglazyme sales and marketing expenses. This is partially offset by the absence of certain acquisition costs for ZyStor therapeutics, which occurred in the third quarter of 2010. Additionally, in the third quarter of 2011, we incurred $1.9 million in costs related to the conversion of a portion of our 2013 debt into equity. Now I'll review the GAAP and non-GAAP bottom line results.

Our GAAP net loss for the third quarter of 2011 was $17.7 million or $0.16 per diluted share compared to a net income of $217.3 million or $1.68 per diluted share for the third quarter of 2010. During the third quarter of 2010, we reversed our deferred tax asset valuation allowance and recorded a one-time benefit of $223.1 million. Non-GAAP adjusted EBITDA for the third quarter of 2011 was $4.6 million or $0.04 per diluted share compared to non-GAAP adjusted EBITDA of $18.1 million or $0.15 per diluted share for the third quarter of 2010.

From a cash perspective, we ended the third quarter of 2011 with $370 million of cash and short- and long-term investments, down from $412.1 million at the end of the second quarter of 2011. During the third quarter of 2011, we recorded $48.5 million for the acquisition of the new manufacturing plant in Ireland. Excluding this impact, our cash balance increased during the quarter.

Turning to the 2011 guidance, we now expect total revenues in the range of $439 million to $465 million. We still expect Naglazyme net product revenue in the range of $225 million to $240 million and Aldurazyme net product revenue to BioMarin in the range of $79 million to $83 million. We are slightly raising the bottom end of our Kuvan expectations from a range of $112 million to $120 million to a range of $115 million to $120 million. We continue to expect Firdapse net product revenue in the range of $13 million to $15 million.

As for expense guidance, we continue to expect positive sales in the range of 18% to 20% of total revenue and SG&A expense in the range of $164 million to $174 million. We now expect R&D expense in the range of $205 million to $210 million from a previous range of $200 million to $205 million. For the bottom line, we still expect GAAP net loss in the range of $43 million to $33 million. We now expect non-GAAP adjusted EBITDA in the range of $45 million to $55 million from a range of $49 million to $59 million.

As a reminder, non-GAAP adjusted EBITDA excludes depreciation and amortization, contingent consideration expense, interest income and expense, income taxes, stock compensation and material nonrecurring items, such as the debt conversion costs. Consequently, the change in non-GAAP adjusted EBITDA guidance is primarily due to the higher R&D spending.

Now I'd like to turn the call over to Steve Aselage, who will provide an update on our commercial business.

Stephen Aselage

Thanks, Jeff. We are very pleased with the performance of the commercial portfolio so far this year. Naglazyme continues to do well with continued geographic expansion as well as additional patients being added in our relatively mature markets. We're pleasantly surprised with the extent of our progress in Russia and have recently opened an office in Moscow. We see Russia as a significant opportunity for both Naglazyme and several of our pipeline products. We have made significant regulatory progress in Iran and continue to believe that despite a somewhat slower-than-anticipated pathway to approval, that there is near-term opportunity there.

We continue to find new patients in more established markets like the U.S. and Western Europe. Q3 continues to be a challenging quarter relative to compliance, as vacation time in many parts of the world caused mis-confusions and resulting loss of revenue. We continue to see steady growth in the number of patients on therapy and remain positive about prospects for continued growth of Naglazyme in the future. As I say every quarter, it is important to keep in mind that quarter-to-quarter sales are subject to significant fluctuations due to the timing of large orders by government entities. And we expect to continue seeing this going forward.

Kuvan is still growing steadily with a 15% year-over-year increase in commercial tablets dispensed. It marks a bit of a milestone that for the first time, over 1 million tablets were dispensed in Q3. We continue our efforts in managing patient adherence and getting previously discontinued patients back on therapy. The neurocognitive study J.J. mentioned earlier, PKU-016, is gaining momentum in picking up enrollment. As expected, the study has had a slightly negative impact on commercial new patient starts. However, the potential long-term impact greatly outweighs any temporary setbacks, and Kuvan is still showing significant growth. The investigator-sponsored trial in autism was presented on October 20. And while there were improvements in several core components of the disorder, the primary endpoint were not hit. While this is disappointing, it's important to realize that results in autism bear no relationship to clinical efforts currently underway treating PKU patients.

Firdapse efforts continue in the EU and have shown modest quarter-over-quarter growth this year. Pricing negotiations are underway in several additional countries. We hope to see contributions from those markets by the end the year. Now I would like to turn the call over to Hank, who will provide an update on our R&D pipeline.

Henry Fuchs

Thanks, Steve. As J.J. noted earlier, the successful execution of our pipeline remains a top priority for the company, and we have made significant progress in advancing our R&D programs during the quarter. At our upcoming R&D day on December 8, we, along with a group of experts, will provide detailed updates on our ongoing clinical and preclinical programs. For now, I'll just provide a brief overview of this quarter's progress.

Starting with GALNS for MPS IVA. Enrollment for the pivotal Phase III trial is accelerating. We are on track to report top line results in the third and fourth quarter of 2012, and to file by either the end of 2012 or the beginning of 2013. Turning to PEG-PAL. Thus far, we know that PEG-PAL is extremely potent and efficacious in almost all patients tested to date. More importantly, as an acceptable long-term safety profile, it is well-tolerated. We're currently exploring different induction dosing regimens to minimize the initial safety reactions that we see in the majority of the patients. We believe it is worth taking the extra time now to optimizing the dosing before proceeding to the Phase III trial.

The Phase I/II trial of BMN-701 for late onset Pompe's disease is progressing on schedule. We have finished the 5-milligram per kilogram dosing cohort and passed the safety review. We completed the enrollment of patients in the 10-milligram cohort and expect to dose our first 20-milligram per kilogram patients by the end of the year. We remain on track to report top line results in the second half of 2012. We also have 2 ongoing trials for our PARP inhibitor, BMN-673. A Phase I/II open-label trial of BMN-673 in patients with advanced recurrent solid tumors and the 2-arm open-label dose escalation Phase I trial in patients with hematologic malignancies. We expect to report top line results from both studies in the second half of 2012. Finally, we are also making progress with BMN-111, the CNP analog for achondroplasia. We remain on track to file the IND by the end of the year and expect to initiate a Phase I trial in the first quarter of 2012.

So as you can see, we have a very well full, diversified pipeline, ranging from preclinical programs to GALNS and a Phase III pivotal study. We'll keep you updated on the progress of our programs as they advance. And with that, operator, we'd like now to open up the call up for questions.

Question-and-Answer Session

Operator

[Operator Instructions] Your first question comes from the line of Salveen Richter from Collins Stewart.

Laura A. Ekas - Collins Stewart LLC, Research Division

It's Laurie Ekas on behalf of Salveen. I guess, just with the delay of the Phase III PEG-PAL study, how much of that is related to identifying the best induction therapy versus sorting out the formulation questions? And where do you stand with the formulation? And I guess, how confident are you that you'll be able to start the Phase III in the second half of the year?

Henry Fuchs

So the primary driver of where we are with PEG-PAL is our desire to get a safe induction regimen. We're very excited about the long-term safety and efficacy profile that we see and we continue to see. So with that, we believe that it is still important to invest and getting patients on therapy in the quickest and safest and most convenient way possible. So that's the primary driver for what we're focused on with PEG-PAL now.

Jean-Jacques Bienaimé

So to answer your question first, Salveen, on the formulation. So the delays is not related to a formulation issue. We're pretty much set on the formulation we're going to use on a going-forward basis.

Operator

Your next question comes from the line of Chris Raymond with Robert Baird.

Christopher J. Raymond - Robert W. Baird & Co. Incorporated, Research Division

Just a question on BMN-701. I could have swore you guys had a 15 mg per kg dose that was between the 10 and the 20. Could you maybe talk to if that was true? Or if there's something -- some decision that was made to go right over to the 20?

Henry Fuchs

Chris, it's Hank. No, there was never a 15. It was always 5, 10 and 20. Sorry, if there was any confusion.

Christopher J. Raymond - Robert W. Baird & Co. Incorporated, Research Division

Okay. And so are you still 3 patients per dose cohort?

Henry Fuchs

Yes.

Christopher J. Raymond - Robert W. Baird & Co. Incorporated, Research Division

Great. Okay. And then a question on the Phe monitor. I noticed in your press release, you'd talked about 2013 having availability. But I understand there's been some developmental sort of snags with that. Can you maybe talk about where things stand in terms of, I think, there was a sensitivity issue?

Stephen Aselage

The Phe monitor, we've talked about on the previous quarter's earnings, we had good sensitivity at the higher Phe concentrations. But when we got down to the lower concentrations, we lost some sensitivity. We believe that's largely due to background noise. We're working through some possible fixes on that, doing some additional testing. At this point, it looks like we should have a reasonable chance of getting the product out to market as stated in the text. But it is a work in progress. And the best I can tell you right now for sure is that we will keep you posted as we make progress.

Christopher J. Raymond - Robert W. Baird & Co. Incorporated, Research Division

Okay. And can you just confirm? The PEG-PAL Phase III does not need a Phe monitor. Is that correct?

Henry Fuchs

Yes, that's our current understanding as well.

Operator

Our next question comes from the line of Joseph Schwartz with Leerink Swann.

Joseph P. Schwartz - Leerink Swann LLC, Research Division

I was wondering if you could talk about the new markets for Naglazyme and in terms of process for gaining regulatory access and generating sales. What is the revenue opportunity in your mind?

Stephen Aselage

We think -- I've mentioned Russia and Iran in the text. To be really candid, we don't know what the opportunity is in Russia. We have visibility that there are a significant number of patients. But there are large portions of Russia where don't have visibility to any patients. And we believe there is significant numbers, particularly in the southern portions. But we don't have people on the ground there. We don't have the ability to penetrate through the entire country. We're starting in the Moscow and St. Petersburg areas. We know there's significant opportunity there and believe that as we expand out beyond that, it could be a very meaningful market for us. We hate to give a specific patient number guess, but I would say we're taking it as a very serious opportunity, that's why we've an office there. We felt it was important to get our own people onto the ground in Russia and to move that market forward as quickly as we can. In Iran, the process has been very time-consuming. First was getting the OFAC authorization from the State Department, then filling a request for authorization. That has come through now, that's gone through the initial committee for funding. There were 30 drugs presented at that first committee meeting, 3 of them were approved for importation. Naglazyme was one of the 3 successful. We've got another meeting that we have to go through to get final approval. But we hope to have that done either by the end of this year or early next year. And again, we know it's a meaningful market, but we don't have visibility down at a granular level that we see exactly how many patients. But similar to other countries across Middle East and North Africa, there appear to be significant opportunities, significant numbers of MPS VI patients there.

Joseph P. Schwartz - Leerink Swann LLC, Research Division

And in terms of the seasonality for Naglazyme, it's a big driver and has a pretty wide 2011 guidance range. I mean, there's just 1 month left. But if you look at those numbers, it looks like sales could be down in the next quarter if you occupy the majority of that range or maybe get back to the $60 million or so level that you're at the last couple of quarters, at the top end of the range. Based on what you're seeing so far in the fourth quarter, would you hazard a guess as to whether you're more likely to come in at the bottom or the top of that range?

Stephen Aselage

One of the things I mention every quarter is that we get large orders from specific governments on somewhat irregular basis, specifically Brazil. There are small entities that order in Brazil on a routine basis. But the Federal Minister of Health orders every 2, 3 or 4 months. And whenever those orders come in, they are very large. And the extent of that order size can be roughly the extent of the gap between the low end and the high end of our range. So you can read between the lines, or I guess, you don't have to because I'm saying it out loud. If the Brazil order comes in, we'll likely to be at the high end. If it doesn't, we're likely to be at the low end.

Jean-Jacques Bienaimé

But in that case, if we are the low end in Q4, Q1 would be pretty stronger.

Stephen Aselage

That's fair to say.

Operator

The next question comes from the line of Robyn Karnauskas with Deutsche Bank.

Navdeep Singh - Deutsche Bank AG, Research Division

It's Navdeep filling in for Robyn. I just had a question on PEG-PAL. What exactly are you doing to identify the induction regimen? And how long is that going to take?

Henry Fuchs

Well, what we're doing is we're collecting a lot of immunology and clinical safety data. And we're trying different schedules and regimens. And it's a little bit difficult to predict how long it's going to take. What we're striving for is the fastest, safest and most convenient regimen.

Jean-Jacques Bienaimé

Induction and titration regimen.

Henry Fuchs

Because once we get patients on therapy, what we've shown is that they can stay on therapy for quite a long time. So we want to have that induction onto therapy be, like I said, that's fast, that's safe and as convenient as possible. And we don't have a precise timeframe for how long that takes.

Navdeep Singh - Deutsche Bank AG, Research Division

Okay. And then just a follow-up. On BMN-701, is there any way we'll get an interim data before the top line?

Henry Fuchs

It's always possible. I'd say make sure you come to Research and Development Day on December 8 in New York City.

Operator

Your next question comes from the line of Liana Moussatos with Wedbush.

Liana Moussatos - Wedbush Securities Inc., Research Division

Can you give us the geographic breakdown of Naglazyme sales?

Jeffrey H. Cooper

Sure. U.S. is $7.7 million; Europe, $19.3 million; and international, $28.9 million.

Operator

Our next question comes from the line of Cory Kasimov with JPMorgan.

Cory William Kasimov - JP Morgan Chase & Co, Research Division

That was a good teaser for the R&D Day. And on 701

for Pompe, what was the hurdles that need to be clear to proceed to each subsequent dose cohort? Is this simply safety check or there are efficacy things in place as well?

Henry Fuchs

Cory, Hank here. Just safety.

Cory William Kasimov - JP Morgan Chase & Co, Research Division

Just safety, okay. Then going to earnings season, it seems like drug pricing has been a big topic of conversation on just about every earnings call this quarter. Can you guys talk a little bit bigger picture about the pricing environment for orphan drugs and maybe some of the regional differences or trends you're seeing there?

Stephen Aselage

Pricing is under pressure. The global economic problems that you read about in paper every day have everybody tightening their belt. Good pricing, good reimbursement is still possible as long as you have a product that provides significant value for the price that you're charging for it and good clinical data to support that benefit. And we're fortunate with Naglazyme to have a product that both provide significant value and as a clinical data to backup that value. We do see a number of things taking place, including more frequent reauthorizations in some countries, higher copays in places, more frequent reviews to maintain or determine that efficacy is being maintained. But to date, we've been able to work through the pricing pressures relatively unscathed with the only 2 major setbacks, the German price cut that took place about a year ago, that mandatory 10%, and the U.S. Medicaid rebate increase that also took place last year.

Jean-Jacques Bienaimé

And to further elaborate on Steve's answer, we haven't seen so far any policy regarding realness [ph] in pricing that specifically targets orphan disease products. So when there was a cut in Germany, summer of last year, it was across the board for all pharmaceutical product. And we were not exonerated, but it was not something that was targeting orphan products.

Stephen Aselage

Maybe to add to that as well, we have looked at some of the proposed changes in the U.S., including expansion of the 340B criteria hospitals. And it is a relatively meaningless change in our overall revenue stream, if any of those changes are put in place this year.

Operator

Your next question comes from the line Eun Yang from Jefferies.

Eun K. Yang - Jefferies & Company, Inc., Research Division

At the recent medical conference, some of the docs mentioned that when they put their patients on Kuvan, about 20% to 30% of their patients haven't been able to offer restrictive diet. Is that what you're hearing in the medical community?

Stephen Aselage

They impact of Kuvan varies by patients. You need residual pH enzyme activity, which Kuvan upregulates as a cofactor. In some patients, that upregulation provides a dramatic drop in Phe levels. And in those patients, physicians tend to liberalize the patient's diet. In some patients, there's no residual activity in the enzyme and there's no impact at all and the patient immediately comes off Kuvan. And another market of patients if you will are patients who do have a drop in Phe level that's beneficial to the patient, but not a drop that's significant enough to allow diet liberalization. Our best market research would indicate that roughly 70% of patients do have some liberalization of their diet after going on to Kuvan. But certainly, there's certain patients that benefit only from the drop in Phe and do not have a corresponding increase in protein intake.

Eun K. Yang - Jefferies & Company, Inc., Research Division

Okay. And then question on PEG-PAL. Phase III initiation starting timeline has been pushed out at each quarter conference call. And Hank, you'd mentioned that it is difficult to predict how long it would take to actually figure out the induction and optimal scheduling in dosing. So are you comfortable with second half of next year Phase III initiation for PEG-PAL?

Henry Fuchs

Well, I think that's our view as we sit here today, and we have more dosing work to do. But it's complicated. And I think we think it's important to get it right. So what I said in my prepared remarks was that given the important and sustained benefits that we see in PKU patients through the PEG-PAL, we think it's worth spending the extra time now to get the induction dosing regimen right. And as far as more details again, I'll just file another advertisement for R&D Day, where we can talk about this in quite a bit more detail.

Jean-Jacques Bienaimé

But we have specific plan in place as to what we are testing right now and what we're planning to test in the next 6 months or so.

Operator

Your next question comes from the line of Tim Lugo with William Blair.

Tim Lugo - William Blair & Company L.L.C., Research Division

Since it looks like that PEG-PAL pivotal trial will be around the same time as the Kuvan outcome study, will the outcome study inform endpoints for the PEG-PAL pivotal trial?

Henry Fuchs

Well, it's certainly good to have knowledge. We think that from a regulatory perspective, the blood phenylalanine level can service the primary basis for approval. We are learning quite a bit about neurocognitive effects of Phe lowering, and there could be some value in including additional measures of executive function in the pivotal trial. We don't think we'll be obliged to do that. And as to whether we choose to do that, I think we have to wait and get a little bit more data from possibly the 016 trial, but also just from assembling more experience in the PKU community and then putting together the final design of the Phase III trial.

Jean-Jacques Bienaimé

Actually, to remind you, in this past summer, we did have a testing [ph] meeting with the FDA on PEG-PAL for potential Phase III primary endpoint. And at that meeting, the FDA told us that our Phe lowering for PEG-PAL will be an okay primary endpoint.

Tim Lugo - William Blair & Company L.L.C., Research Division

Okay. And can you remind us on the IP surrounding Kuvan and your expectations for Paragraph IV? Do you have a hard line whether there will be a settlement or some sort of legal battle on what the timing would be of that?

Jean-Jacques Bienaimé

Well, again, and I hate to say that again, but we were planning on giving you a thorough presentation on the IP situation with Kuvan at the R&D Day. But the first Paragraph IV filing could occur as early as December 13 of this year. However, whatever the timing of this filing, the worst-case scenario is in this we have orphan drug protection and we have pediatric claims. So that's a very, very -- it's very early. If all our IP protection failed, the very earliest time that generics would come in would be the mid-2015. But as you will see in our R&D Day, we've been gearing up for a big legal battle. I think we anticipate a legal battle. We've been preparing for it for over a year. And we have several issued patents now, including the once-a-day patent which we think is very strong. So again, we'll give you an update on December 8.

Operator

Our next question comes from the line of Brian Abrahams with Wells Fargo securities.

Shin Kang - Wells Fargo Securities, LLC, Research Division

This is Shin calling in for Brian. I have a question on BMN-701 in Pompe's disease. You've talked a lot about a goal of showing superiority over Myozyme and Lumizyme. I know the study is still kind of early in early phase of the study, but it would be helpful if you could talk a little bit about how large the study has to be in order to show superiority, particularly as to the 6-minute walk test and/or FEC [ph]?

Henry Fuchs

Yes. So I think it's important to remember that the present study, the dose escalation study followed by a cohort expansion is a single-arm, noncomparative trial. So the interpretation of the trial will be based on a comparison to what amounts to a historical control group, which will be the published data on Myozyme, Lumizyme that was the basis for its approval in late onset Pompe's. And I think we're focused on 2 things there. One was a group mean improvement in the 6-minute walk test in the Myozyme group, which was around 28 meters. But maybe more importantly, if you look at the individual patient data from that study, out of 60 patients randomized and received Myozyme or received Lumizyme, only 4 of the patients had really very large improvements in their 6-minute walk test. And so I think our principal interpretative frame of reference using that historical control group is rather that we're better than 4 out of 60 or roughly 1 out of 15. And we think that in the cohort expansion group, that if we see a response rate which is substantially in excess of that 1 out of 15 rate, we would be very encouraged to take that into a clinical trial.

Jean-Jacques Bienaimé

To expand on this, though, I mean, I don't know if I [indiscernible] your question. Obviously, we have little time to finalize the design of the Phase III trial. But as where we stand today, we don't believe it will be necessary to do a side-by-side comparative trial to Myozyme, Lumizyme. Probably we will do a placebo-controlled trial Phase III, and then likely [indiscernible], we would do a switch trial, where we would take patients that are currently on Myozyme or Lumizyme and switch them to 701 and see what happens. We don't believe there's a need for a side-by-side controlled trial comparing our product side-by-side to Myozyme.

Operator

Your next question comes from the line of Nicholas Bishop with Cowen and Company.

Nicholas Bishop

I just have a couple of questions about what you've learned so far about the rash that's associated with the induction phase on PEG-PAL. And those questions are what kind of data about what underlies that [ph] type? Can we expect to see it at the R&D Day? And second, will we see any of the results of your titration study at the R&D Day? And finally, based on what you know so far, is there hope that, that rash in most patients could be reduced or eliminated in the future?

Henry Fuchs

Yes, so the kind of data that you're going to see on R&D Day pertains to the clinical safety profile as well as the laboratory measurements that have been made in the trial, particularly around inflammatory and immune parameters. And as to exactly what's going to be presented, I think it's a little early still to talk about exactly what's going to be presented. But I think it will be a fairly comprehensive presentation of where we are with PEG-PAL and where we're going.

Nicholas Bishop

Okay. And are you hopeful that if you optimize the titration schedule, you could avoid the rash [ph] type in most patients?

Henry Fuchs

We've seen varying frequencies of the rash according to different regimens. And we're pretty confident that we can find something that's acceptable in terms of frequency. And we're just trying to optimize, as I said before, the frequency of that side effect, the time it takes to get patients on therapy and the simplicity and the convenience of that regimen.

Nicholas Bishop

Okay. And just one quick other one on Firdapse. I didn't -- maybe I missed it, I didn't see it in the release, when the data from the U.S. trial might be available.

Jean-Jacques Bienaimé

Probably in the second half of the next year.

Operator

Your next question comes from the line of Alan Leong with Biotech Research.

Alan Leong - Biotech Stock Research

I wondered if you can update us on the infrastructure expansions.

Henry Fuchs

The what?

Jeffrey H. Cooper

The infrastructure expansions.

Stephen Aselage

Are you asking about the manufacturing acquisition? Environment?

Alan Leong - Biotech Stock Research

Yes, both the acquisition and the domestic expansion.

Jean-Jacques Bienaimé

Is your question set around manufacturing?

Alan Leong - Biotech Stock Research

Yes.

Jean-Jacques Bienaimé

So as you know, we closed on the acquisition of the facility in Ireland at the end of August. So this facility is not ours. As we had communicated, we have decided to kind of mothball this facility until we get the results of the GALNS Phase III trial. So we only have about 12 people in the facility at this time, down from about 70, 75. And our plan is to as soon as we get what we anticipate will be positive results from the Phase III trial, we will rehire a substantial number of people over there so that we can start activities regarding preparing the facility for qualification for GALNS manufacturing because the rationale behind acquisition was related to the fact that between -- with the 2 plants that we have now in Novato in California, we have enough capacity to get started with GALNS, in addition to the other products we have on the market or in development. But assuming GALNS is as successful as we anticipate, we would need additional facility. But by the time we get to a level where we need that capacity, the Shanbally facility will be probably hopefully validated and approved. Regarding the extension or the second facility in Novato, we are in the final stage of getting that facility qualified. And we anticipate at this time that the facility should be qualified for and approved for manufacturing of Naglazyme probably by the end of next quarter. And then we are starting the qualification activity for GALNS. And we anticipate then this facility to be approved for GALNS, manufacturing right before GALNS approval anticipated in late '13.

Alan Leong - Biotech Stock Research

That's great to hear. In the announcements, you mentioned that there were other candidates that haven't been announced yet. When will the next candidate -- when will you plan for the next candidates to be announced? And if you can, could you characterize -- is there any way you could characterize the candidates you have in the background?

Jean-Jacques Bienaimé

No, we don't want to tell you much information. But what we can tell you is that BioMarin remains focused on orphan disorders, and so this will be -- the next candidate will likely be a product for another orphan disorder and we always try to look at disorders that have no approved products at this time for that indication that would be a significant improvement in terms of efficacy or safety as compared to whatever is available in the market. As to the timing of when we're going to disclose that, I don't really want to say much about that yet.

Operator

You have no more questions at this time. I would now like to turn the call over to Mr. Bienaimé for closing remarks.

Jean-Jacques Bienaimé

Okay, thank you. So in summary, our commercial portfolio continues to generate sufficient cash to fund the development of our R&D pipeline. This year has been an important building year for the company. And as we look forward to many peak readouts, data readouts in 2012, and let's say, before by the end of next year, we'll have results for the Phase III GALNS, the Phase I/II trial for 701 for Pompe, the neurocognitive trial for Kuvan, and the Phase I/II trial for BMN-673 for genetically defined cancers. So all of these could have very important implications for the future of the company. So we look forward to keeping you updated on our progress and thank you for your continued support and for tuning us on today's call. And goodbye.

Operator

Thank you for your participation in today's conference. This concludes the presentation. You may now disconnect. Good day.

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