Eugenia Shen Jean-Jacques Bienaim - Chief Executive Officer and Director Daniel K. Spiegelman - Chief Financial Officer and Executive Vice President Jeffrey Robert Ajer - Chief Commercial Officer and Senior Vice President Henry J. Fuchs - Chief Medical Officer and Executive Vice President

Matthew Harrison - UBS Investment Bank, Research Division M. Ian Somaiya - Piper Jaffray Companies, Research Division Salveen J. Richter - Canaccord Genuity, Research Division Matthew J. Lowe - JP Morgan Chase & Co, Research Division Christopher J. Raymond - Robert W. Baird & Co. Incorporated, Research Division Yaron Werber - Citigroup Inc, Research Division Brian Corey Abrahams - Wells Fargo Securities, LLC, Research Division Michael J. Yee - RBC Capital Markets, LLC, Research Division Ying Huang - Barclays Capital, Research Division Liana Moussatos - Wedbush Securities Inc., Research Division Kimberly Lee - Janney Montgomery Scott LLC, Research Division Nicholas Bishop - Cowen and Company, LLC, Research Division Michael W. Schmidt - Leerink Swann LLC, Research Division

Good day, ladies and gentlemen, and welcome to the BioMarin pharmaceutical Inc. Fourth Quarter and Full Year 2012 Financial Results Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded. I would now like to introduce your host for today's conference, Eugenia Shen of Investor Relations. Ma'am, you may begin.

Thank you. On the call today is a J.J. Bienaimé, BioMarin CEO; Dan Spiegelman, CFO; Hank Fuchs, Chief Medical Officer; and Jeff Ajer, Chief Commercial 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 programs, 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 the 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. Bienaimé, BioMarin's CEO.

Thank you, Eugenia. Good afternoon, and thank you for joining us on today's call. As we wrap up 2012 and set our sights on key 2013 milestones, I would like to share some thoughts of -- over the past and what is ahead for BioMarin. At BioMarin, our strategy is develop first-in-class or best-in-class therapies where we can make a big difference in the lives of the small number of patients suffering from rare or ultra-rare diseases. That strategy bore fruit in 2012. They set us for further growth in 2013 and beyond. 2012 was a milestone year for BioMarin on a number of important fronts. On the commercial side of our business, we reached the $0.5 billion revenue level. And with a direct commercial presence in 26 countries and products available in more than 40 markets worldwide, we expect to see revenues from our first-in-class commercial therapies to continue to grow. On the development side, we announced positive results for our Phase III Lumizyme study, and we expect to file for approval in the U.S. and EU over the next 2 months. We also announced positive results from our PEG-PAL Phase II study, and we plan on initiating a Phase III next quarter. Overall, we made continued progress on our rich development pipeline. And as a result, we expect to have 6 programs in the clinic this year, the most ever at BioMarin, and one of the richest pipelines for a company our size. As we start 2013, we're excited about a potentially transformative event set with a number of key milestones coming up in the next few months. The filing of Vimizim VLA remains on track for later this quarter with a potential approval and product launch before year end in the U.S. Vimizim could be our largest…

Thanks, J.J. I will start by reviewing product revenues for the full year 2012, and then follow with a more in-depth look at our operating expenses and financial results before turning to guidance for 2013. Total revenue reached the $0.5 billion milestone in 2012, coming in at $500.7 million, a 13.4% increase over a total revenue of $441.4 million for the full year 2011. For our lead product, Naglazyme, net product revenue was $257 million for the full year, a 14.3% increase compared to $224.9 million for 2011. Changes in foreign currency rates net of hedges had a negative $0.9 million impact in 2012. We are encouraged by the continued steady growth in the number of patients on therapy, primarily from established markets. Net sales of Aldurazyme by Genzyme were $193.1 million for the full year 2012 compared to net sales of $185.2 million for 2011. Net product revenue to BioMarin related to Aldurazyme was $82.2 million for the full year compared to net product revenue of $82.8 million for the full year 2011. Net product transfer revenue had a positive $1.8 million impact on net Aldurazyme revenue to BioMarin for the full year 2012. Net product revenue for Kuvan of $143.1 million for the full year 2012 represented a 22.5% increase compared to $116.8 million for 2011. Now I'll review gross margin operating expenses and other items in more detail. For the year ended December 31, 2012, gross margins were 85% for Naglazyme, 68% for Aldurazyme, and 83% for Kuvan, consistent with prior years. Research and development expenses were $302.2 million for the full year 2012 compared to $214.4 million for 2011. The increase in R&D compared to last year was primarily driven by increased Vimizim clinical trial and manufacturing expenses. R&D expenses also increased due to clinical trial…

Thanks, Dan. Revenues from total product sales in the fourth quarter reached $131 million, an increase of 23.5% over the prior year quarter. In the fourth quarter of 2012, there were no disruptions to supply or abnormal ordering patterns in territories such as Brazil, where shipments have been pushed out to the first quarter for the past couple of years. Naglazyme sales were driven by net patient gains principally in our major established markets and continued high levels of compliance with treatment. Net product revenue increased 14.3% in the year ended December 31, 2012, over the prior year, which is roughly proportionate to the growth of new patients on therapy and continued growth that we think is sustainable. While government order patterns sometimes result in choppy revenue quarter-to-quarter, growth in the number of patients on therapy continues at a steady rate. As always, we advise you to look at annual revenues and guidance rather than quarter-to-quarter changes to gauge growth of our Naglazyme franchise. Kuvan sales maintained a steady level of growth with a 22.5% increase in the full year 2012 as compared to the full year 2011. Factors driving growth include: continued growth in demand from new patients starting therapy, and high levels of compliance and persistence. We are encouraged by the results of the PKU-016 study and are exploring how we can use this data to better educate physicians and others in the PKU community about the severity of the disease and the potential benefits of Kuvan. As for Vimizim launch preparations, we are continuing with our patient identification and patient mapping work, which will be an ongoing effort throughout this year. To better educate the medical community and to prepare the market for the Vimizim launch, we are increasing Morquio A disease awareness and highlighting the serious multi-systemic nature of the disorder. Finally, in anticipation of the late Q4 2013 approval and launch, we are planning to do some modest hiring later in the year and mainly in the United States. Now I'll turn the call over to Hank Fuchs, who will review the pipeline.

Thanks, Jeff. As J.J. noted earlier, our commitment to advance the pipeline is beginning to result in value-generating milestones as we look forward to several more important events in the coming year. Starting with Vimizim for MPS IVA, we are busy with preparations to submit the first market authorization application by the end of the current quarter. We have met with our rapporteur and co-rapporteur, who will process our market authorization applications for the EMA. And we are encouraged by their feedback and believe we have all the information necessary to file for approval and initiate the approval of the dossier. In addition, we have met with the Food and Drug Administration and confirmed our submission content, therefore, we plan to submit first to the FDA by the end of March and then to the European regulatory authorities in April. The 3 ancillary studies are ongoing, but we do not believe that they will be required for submission or review. As J.J. mentioned, earlier this week, we announced the preliminary results from PKU-016, Kuvan neurocognitive study. The study enrolled 206 phenylketonuria patients, approximately half or 118 of whom were found to respond to Kuvan with a reduction in their blood phenylalanine levels. Inattentiveness is a major problem in PKU and nearly 1/3 of these patients had a medically significant degree of this disorder. The studies predefined analysis population therefore focused on measuring the improvement in Attention Deficit Hyperactivity Disorder rating scale or ADHD-RS, a commonly used tool for the evaluation approval of medications for patients with ADHD. In the 38 patients in the study with inattentiveness symptoms who respond to Kuvan with the reduction in Phe levels, Kuvan demonstrated a meaningful trend toward improvement of symptoms compared to placebo as measured by the primary endpoint of ADHD-RS. Now the result…

[Operator Instructions] Our first question comes from Matthew Harrison of UBS.

First, Hank, if I can start with 701. So -- and I might have missed part of this. So you said 15% or greater improvement on 6-minute walk, 1% of super responders, and 10% on SCD 1. Can you just walk through -- I think, when I've looked at the data before, I think some of us might have been thinking it, you were looking for maybe a higher improvement, so just help us think about what criteria you guys used to set that bar. And I think the other question is, when you look at mean 6-minute walks, you get a lot of super responders, obviously that moves up compared to LOTS. How do you think about that interplay as well?

Yes, so just to clarify. The menu is 3 items: the 1% super responders, mean improvement for the population of 6-minute walk or respiratory parameters. It's either 15% of 1 or 10% of 2 of the parameters. How did we set that? We had a lot of interactions with opinion leaders, asked them what would represent a clinically significant improvement for their patients, and basically, reduced that conversation to a consensus set of numbers that I just recapitulated. And to illustrate, for example, in the case of Myozyme in the LOTS trial, about 7% of patients were super responders. If we observed 15%, the clinicians would view that as clinically significant. Or in the LOTS trial, there was a mean improvement in walking distance of 25 meters, less than 10%. A 15% improvement from baseline would be viewed as clinically significant. So 15% of any 1 of the parameters or 10% or more of 2 of the parameters.

Can I just ask a follow up then? So 15% of, let's say, super responders is 2.5 patients, let's call it 3. It's a small number from a small subset. How do you -- and I think -- and you'll remind me, but LOTS I think had 3 super responders as well. I mean, obviously bigger denominator. Just how do you get comfortable that that's enough patient that you haven't, somehow, selected certain patients with certain baseline criteria?

Yes, that's a very important question, and I think that was one of the focus points of the discussion at the WORLD Lysosomal Storage Disease Symposium. And Dr. Byrne addressed that directly by going through the baseline demographics of our study compared with that, that was published in LOTS, and demonstrated that, quantitatively, our patient population is substantially similar to the LOTS patient population. I have to say that if you ask opinion leaders what would be a clinically relevant improvement, they tend to first answer the question with anything over what we've already seen would be clinically relevant. So we have set the bar quite a bit higher than that for the simple purposes of assuring us that when we conduct our Phase III program, we'll end up with outcomes that do demonstrate superiority quantitatively.

Our next question comes from Ian Somaiya of Piper Jaffray.

I'm just going to follow-up on the BMN-701 questions. Question on the new cell line, maybe if you could just walk us through what enabled you to accelerate the timelines there. And what if the new cell line allows you to maintain reasonable gross margin while exploring potentially higher doses as you move into Phase II/III study, the difference relative to LOTS and the potential could be greater?

Yes, so in terms of the acceleration, before we had a lot of data about the new cell line, we wanted to be very cautious about what the impact on time was going to be. We've now seen enough of the data to where we think we can map the path to using the new cell line in the clinic. We think we have a good grip on the biochemistry, the animal pharmacology and expected toxicology program that would enable entering into that Phase III -- II/III program. And I think today, as opposed to before, all of these analysis were included, we have increased confidence that at the end of this year is a reasonable time to aim for. As far as doses, the primary driver switching to the new cell line, as we've talked about before, is the efficiency of manufacturing. We don't have plans to go to higher total doses of protein administered, at least in the short term. 20 milligrams per kilo is -- on an every other week schedule is a pretty large amount of protein dose. We think that, that with the increased potency of 701 versus Myozyme that we're going to deliver approximately 5x more enzyme for the lysosome and therefore test and ultimately prove that improved delivery to the lysosome results in improved glycogen clearance and in improved strength.

And to you expand on -- J.J. here. To expand on the tax response. I think you had a question on cost of goods. So, yes, the anticipated dose with the new cell line will be 20 milligram per kilogram every other week, so the same as what we are anticipating for the old cell line. The productivity of the cell line is apparently right now we estimate between 2.5x and 3x of the productivity of the current cell line. And subsequently considering if you just look at the cost of Lumizyme today in delta [indiscernible] divisions, we anticipate that with this current cell line, we should be in the usual gross margin profile for enzymes.

And if you don't mind me just asking a quick follow-up. The parameters you have set for making a go decision on the Phase II program, are those the same ones that your advisers have said as enough to entice switching away from Myozyme and Lumizyme?

Hank [indiscernible] and it operates. I think, in the most part, we're above where the key opinion leaders have told us it will induce switching on their part. Hank?

Yes, I think, Ian, I think you've really hit on a key issue. And that is that having -- if we conclude go on the basis of a study on naive patients, the next critical question to ask is, can you improve patients who are already on Myozyme or Lumizyme? That question is immediately germane to the currently prevalent market of patients. There, as I said, opinion leaders would accept any level of improvement, as J.J. just re-reflected. Any level of improvement might be difficult to establish, so we set the bar higher than that to assure that when we do a switching study that it's reasonably likely that we're going to meet a successful outcome. But I think it's, at this point, worth pausing and saying, we haven't analyzed all the data. When we do that, we're going to share that data with you, and we'll take you through what our findings are and get more explicit about the basis of our decision.

Our next question comes from Salveen Richter of Canaccord Genuity.

Just another one on Pompe. So the hypoglycemia that we saw and the glycogen reductions that were in few of the biopsy patients, how do you expect that to translate into efficacy with 6-minute walk distance and the other measures?

Well, the hypoglycemia is kind of an expected pharmacologic effect, and I don't know that -- it's an infusion associated event. I don't know whether we will or won't be able to correlate that with clinical outcomes. But in terms of glycogen clearance, Dr. Byrne did show 3 -- the 3 patients in the study who were at his institution who had pre- and post-701 muscle biopsies and quantitative assessments of glycogen. He showed a small improvement in muscle glycogen in the 2 patients treated at the low dose and a very large improvement in muscle glycogen in patients treated at the high dose. What's been seen in preclinical studies of Myozyme and 701 is that a 20 milligrams per kilo Myozyme barely clears any glycogen. And clinically, at that same dose, Myozyme has some effect, but not a very large effect in patients. And what we've shown in Pompe knockout mice is that in contrast, at 20 megs per kilo, 701 substantial -- clears substantially more glycogen from the muscle of a Pompe knockout mouse. And we've now shown in a very small number of patients substantial clearance in glycogen from humans. The next piece of information that we don't yet have, but would like to have is did that clearance of glycogen translate into improved clinical outcome? And so if it does translate into approved clinical outcome, we would establish a nice chain of prediction of relative potency of clearance of glycogen in preclinical species to glycogen clearance in humans to clinical correlates.

Great. And just to follow-up. I think previously you've guided to maybe starting the Phase II/III at the end of 2014 due to manufacturing verification and inventory building. And now it's been moved earlier to the end of 2013, just wondering if anything changed -- what changed here to cause you to move this more rapidly?

Well, as I said, previously before we had a lot of data on the manufacturing side, we were guiding to be relatively conservative, so that we -- so that we didn't miss that expectations. At this point now we've seen the data on the biochemistry of the produced product, and we have a better understanding of the requirements to produce the product, the biochemistry of the product, the animal pharmacology of the product, a substantial amount of information on the toxicology of the product. And on that basis, we have a pretty good understanding of what it's going to take to get back into the clinic. The additional thing I'd say is that we're also getting a little bit more clear from our conversations with opinion leaders as well as from the study of the regulatory landscape about the requirements for registration support. And as I think I've mentioned before, what's clear is that a switching study would be required to support the registration of 701. And a switching study is something that we can start relatively readily, we believe, with the material from the new cell line. So it's putting together all of those pieces with a lot more information in hand today than we had previously that causes us to revise our guidance to the starting time of 701.

Our next question comes from Cory Kasimov of JPMorgan. Matthew J. Lowe - JP Morgan Chase & Co, Research Division: It's actually Matt Lowe in for Cory today. I was just wondering, as you get feedbacks from KOLs? What are your updated thoughts from the pivotal trial design for 673? And then just a second question is of the multi-year patients you've already identified, I guess how many are there and approximately what percentage of those are living in the U.S.?

So in our interactions with opinion leaders on 673, I think there's a ready substantial acceptance and validation of the activity of PARP inhibitors in advanced refractory metastatic ovarian cancer. And there is a tenable regulatory path for the development of a PARP inhibitor in ovarian cancer, and we're really excited about the data that we have, I think, at our last update. Numerically, we mentioned that even during the dose escalation phase, we have an objective response rate to 673 of 67% and disease control rate of 92%. That's really a pretty fantastic level of activity even compared to competitors adding dose, by the way, that's orders of magnitude lower than competitors. But we are cautious about jumping into ovarian cancer directly. We're going to be obtaining data on BRCA mutant breast cancer patients as well as Ewing's sarcoma and small cell lung cancer. And these tumors have the interesting potential advantages of faster time-to-market and potentially even higher probability of success. So we believe that it's worthwhile to get additional data before declaring what our Phase III program is before committing specifically to the Phase III program. And so our expectation that we will be able to make that call and get into Phase III by the end of the year, look for an update at ASCO. And as far as your MPS question, I'll turn that over to Jeff.

We've identified over 1,200 Morquio A patients to date around the world, 20% of which are located in North America, and that would be a combination of the United States and Canada.

Our next question comes from Chris Raymond of Robert Baird. Christopher J. Raymond - Robert W. Baird & Co. Incorporated, Research Division: Just quickly, I know a lot of folks have asked questions on 701, but I just -- can you clarify, so, Hank, are you saying that a bridging Phase II study is now not necessary? Is that what I'm hearing in terms of having your understanding of the new cell line?

I didn't say that. I didn't say that explicitly, but I think that's not an unreasonable inference from my comments. We think we have a pretty good understanding of the biochemistry of the new cell lines manufactured product, pretty good understanding of biochemistry pharmacology, preclinical toxicology. And we believe that it's reasonable to expect that we can initiate a Phase II/III switching study by the end of the year. As to exactly what happens between now and the end of the year, I say stay tuned. We have certainly further conversations to have with health authorities and opinion leaders as to the design, the exact design of that program. Christopher J. Raymond - Robert W. Baird & Co. Incorporated, Research Division: Great. And then maybe just a quick follow-up on PEG-PAL. So we noticed that Merck has opt-in rights. As I understand, it's in Europe, for a pre-Phase III. That's a pretty significant delta on what they pay in terms of Phase III going forward they opt in before or after Phase III starts. Can you sort of talk a little bit about that process, where things stand and what are the -- what are the drivers there for making the decision? Is it up to the day you start the Phase III, or is there some other mechanism?

Yes, so -- this is Dan. They have -- their decision point is up until we enroll the first patient, I believe. And the issue for them is that, if they opt in before we start the study, the pay 50% of it. If they opt in at the end, because presumably they wouldn't opt in the middle, they have to reimburse us for 100% of it. Their decision [indiscernible] is also impacted by the fact that we can't -- because Kuvan and PEG-PAL have overlapping patient populations, even if they don't opt in, we can't commercialize PEG-PAL outside the United States until they do opt in. Christopher J. Raymond - Robert W. Baird & Co. Incorporated, Research Division: And is there a milestone payment on that decision, can you remind us?

Yes. I don't recall what it is. It's not substantial. The bigger driver is the reimbursement of the cost.

[Operator Instructions] Our next question comes from Yaron Werber of Citi.

Just 2 -- it's 1 question, sort of, in 2 parts. It's -- I heard what the operator said. I figured I'll get around it. And it's sort of really 2 parts. Related to tax rates. So how does the new Irish facility impact your tax rate? And then two, can you just remind us for PEG-PAL and Vimizim and 701 and 673, where is the IP residing for these drugs, is it U.S. or offshore?

Sure. So the Irish facility, when -- from all 4 of those are -- the IP for all of them is offshore. So we have the potential, as long as we're manufacturing them either in the Irish facility or otherwise outside the United States, we have the opportunity to get the lower Irish deferral tax rate of 12.5%.

Our next question comes from Brian Abrahams of Wells Fargo Securities.

I'm going to shift gears to GALNS or Vimizim. I was wondering what you guys are seeing in the ongoing extension study with respect to patient retention. And really how similar or different it is to other enzyme replacements in your experience? I'm curious whether there may be any patterns as to who, if anyone, might be discontinuing? Is it based on age or functional benefits on 6-minute walk?

Retention in the extension studies have been absolutely fantastic. And it's very difficult to compare or to establish patterns in the patients who don't continue to the ones who do continue because the number who don't continue is astronomically small. And in fact, it's been -- in rare cases where there has been some discontinuation, it's been mostly logistics, patients from overseas, who went to a treatment center in another country to participate in the Phase III trial. So the main message is retention fantastic.

That's very helpful. And when might we expect to see that data and how important will it be from a regulatory perspective?

We'll continue to provide health stories, updates on safety through the submission process. And I wouldn't expect there to be a next data cut probably until the end of this year. And as I said, I don't think -- well, we don't have an expectation that those extension data are going to be germane in a major way to the -- to help authority deliberations. And as I said in my prepared comments, we think we understand what they require for submission review and approval, and we have that information.

Our next question comes from Michael Yee of RBC Capital Markets.

Sorry, just to clarify your criteria on 701. Sorry to go back to that. You're looking for a 10% and/or a 15% improvement on 1 or 2 of the different criteria. I assume that's a 10% or 15% improvement above the 15% improvement they've already been seeing. So for example on 6-minute walk, the 25% is -- I don't recall what that is, the 15% approval, so you're looking for a 25% improvement over baseline, is that the right way to think about it? And how do you assume for a placebo response in any of this stuff given that you're single-arm versus their controlled study.

No, it's not an improvement over the Myozyme. It's improvement over the patients own pre-treatment baseline. And our expectation in terms of placebo response -- excellent question, a question that was actually raised in a scientific meeting. Our expectation is the effect of placebo in these tests will be 0. If you look at the control arm of the Myozyme pivotal trial, placebo change in 6-minute walk test after 70-something weeks was minus 3 meters, and the change in respiratory function was around minus 1% or 2% for FDC. And for the maximum ventilatory pressures was around minus 0.5%. So there's not much of a placebo effect in these tests.

Our next question comes from Ying Huang of Barclays.

Number one, Hank, can you please confirm that the way you define response is the same as the last round, that is more than 100 meters increment in 6-minute walk. And then secondly -- I'm actually asking this on behalf of some investors that would send me questions by e-mail. Are these new criteria to define a go and no go decision reflective of what you have seen so far from the 10 patients that have already completed dosing in the BMN-701 trial?

Yes, so there were super responder threshold -- it was a good question. And you have to remember -- first of all, it's not our criteria around what this number is. This just simply comes from an FDA advisory committee presentation of a data. What I encourage you to do is to look at a comparable time point for decision making. And in the LOTS last trial, the LOTS trial went to 70-something weeks. But our trial, our decision point is going to be made at 24 weeks. And if you look at those data, you'll see that there are few patients, like I think 4 out of the 60, who at 24 weeks have a superior response. And there's pretty clear zone between those 4 patients and the rest of the population. I think the threshold there is around 75 meters. One could have an argument about whether it's 75, 73, 71 or 70 or 68, but it's around there. And as to, is -- are these decision criteria based on having looked at the data? We've been very careful in working with the opinion leaders to get their unbiased assessment of the go criteria. And so the answer to your e-mail friends is categorically no. These are unbiased assessment of go/no go criteria.

Our next question comes from Liana Moussatos of Wedbush Securities.

I just have a quick follow-up on the impact of the Irish 12.5% tax rate. Going forward, what would the -- how much of an impact will that have on a blended tax rate?

Well, it depends on the mix of revenues. If the revenues from Vimizim and the other offshore products represent 50% of our total sales, I think you could look for a blended tax rate in the 25% range. If it represented 2/3 of our sales, you could look at one -- you'd look at a blended rate that looks like closer to 20%, 18%.

Our next question comes from Kim Lee of Janney Capital.

So just a couple of questions on PEG-PAL and Kuvan. What exactly, for PEG-PAL, was the feedback from the FDA meeting? How is this trial design different from your Phase II? And when do you expect that interim data? And for Kuvan, with the potential label expansion to include ADHD, how much do you think the market could expand?

Well, the feedback that we've got from the FDA is more or less precisely what we characterized in my prepared comments, that is to say that they -- that while they indicated that they may require some additional neurocognitive data for a full approval in adults, they've also indicated that phe lowering alone could substantiate an accelerated approval. As to the timeline of all of that, we are planning to field these trials in the next -- in the coming quarter, but we have not given any kind of guidelines in terms of expectations on enrollment rates or when an application could be made. And I will turn the second part of the call -- the question over to Jeff.

So we're very optimistic about the results from PKU-016. In fact, our clinician patient and payor communities have been asking us essentially since the launch of Kuvan to validate what has been noted anecdotally, and that is the clinical improvement in these patients with PKU that are responding to Kuvan. I would also note that data will be presented scientifically later this year in the fall in a couple of scientific meetings. So the timing of when the clinicians will see that data will be late this year. The impact will probably be felt starting in 2014. I would also note that Kuvan, in terms of its life cycle, will have been on the market for a full 6 years by then. So that's a lead in to say, this data will have a positive effect on the sales of Kuvan. It will not shift the demand curve. It is likely to keep the demand curve going in its current positive trajectory, possibly a little higher.

Our next question comes from Nicholas Bishop of Cowen and Company.

Just a follow-up on PEG-PAL. The new commentary from the FDA is that phe lowering alone is not the sort of full approvable endpoint seems to be a bit of a change in commentary from what you've mentioned before. And I'm wondering just what's different now and what's your level of confidence that you can gain approval on that endpoint alone? And then secondarily, it seems to me there's some challenge in defining a newer type of instrument that will detect the difference in patients without ADHD symptoms baseline? And just can you explain a little bit what you envisioning the full trial is looking like in terms of endpoints and size?

Yes, that's a good pickup, and we -- I think you've got it exactly right there. The FDA did change their feedback to us. We had met with them 1.5 years ago on the PEG-PAL program and had confirmed that blood phenylalanine levels would be sufficient for registration of PEG-PAL in phenylketonuria. And at this meeting, they pushed back a little bit from that by saying they may require neurocognitive data. Exactly what drove that is a little hard to put a finger on the pulse of. It's maybe a mixture of wanting to see more information in adults than just adult and children about blood Phes, validation as a marker of clinical outcomes in patients. It may just be spacing FDA, raising the bar because now is the time that they can raise the bar. But the nut of that is that they also said that the drug could get approved for blood Phe lowering, albeit it would come with post-marketing commitment in the accelerated approval format. We're actually -- none of that actually changed our program at all. We are planning to do that all along. And I think the other thing that happened over the course of this quarter was we actually demonstrated an improvement in neurocognition using a pretty garden-variety-neurocognitive tool, the ADHD-RS scale. And so as much as that might have been a setback, it's not only made up for by the fact that the FDA has offered accelerated approval opportunities, but even better is the fact that we can show what Kuvan and improvement in a standard measure of attention deficit. Now the thing that you have to keep in mind about all this is that in the Kuvan patient population, we get about a -- we have a fairly mildly affected patient population, blood Phe on accounting levels around 800 micromolar at baseline, reduction of blood Phe levels of about 30% down to about 600. In contrast, PEG-PAL patients started about 1,300 or almost 50% worse than their Kuvan counterparts. And their blood Phe levels don't go down to 600 as they do. With Kuvan, they go down to 400 or lower on an average with PEG-PAL. So we have a sicker population with a more effective drug and an instrument that we've now actually piloted and demonstrated to be sensitive to improved neurocognition. So we're feeling pretty good about the opportunity to hit neurocognitive endpoint in our coming PEG-PAL trials. And the FDA has given us a safety net that says, if you don't get it at the first whack, you can talk to us about accelerated approval. So we're feeling pretty good net about PEG-PAL for PKU.

And I may add to this that indeed the FDA actions in mind, we will have to provide neurocognitive data to get full approval. But the good news is, compared to our previous plans, if we do go for the accelerated review pathway -- accelerated approval pathway, we now could potentially file as early as late 2014 and potentially be on the market in late '15, which is earlier than we anticipated.

Our next question comes from Michael Schmidt of Leerink Swann.

I just have one follow-up on 673, the PARP inhibitor. You said you haven't decided yet what indication you will be studying in Phase III. But I guess, I assume now no matter which account it will be, is it fair to assume that there'll be some sort of genetic screening or genotyping that's necessary, too, to define the patient population better? And if so what would the regulatory requirements would be for a potential diagnostic to go along with 673?

Yes if BRCA, no if Ewing's or small cell. All Ewing's and small cell appear to be molecularly sensitive. And as far as co-diagnostic requirements, our belief is that currently available assay to diagnose BRCA is sufficient for certainly running the trials if not registration. And of course, the complete answer to that question is incomplete until we've had -- the full answer to that question is incomplete until we've had more conversations with health authorities about requirements for registration, and we're not there yet.

And our final question comes from Chris Raymond of Robert Baird. Christopher J. Raymond - Robert W. Baird & Co. Incorporated, Research Division: Sorry, my follow-up was asked and answered.

And at this time I'd like to turn the call back to management for any further remarks.

J.J. here. So in summary, I think we are very pleased with the steady growth of our commercial portfolio and the advancement of our pipeline, which is resulting in value generation for the company. We are looking forward to many clinical milestones in the coming years, and with PEG-PAL, BMN-111 and BMN-190 all moving to the next phase of development. We have Phase I/II readout for BMN-701 and 673, and go/no go decision on whether to proceed to Phase III development for this program in the next few weeks or months. We also look forward to a possible FDA approval for Vimizim by the end of the year. It should be a transformative event for the company with a potential to double our revenues and lead us on a path to achieving substantial and sustained profitability. Thank you for your continued support and for joining us on today's call. Good-bye.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program. You may all disconnect. Everyone, have a great day.