Welcome to the BioMarin Conference call to discuss European approval of Roctavian. Hosting the conference call today from BioMarin is Traci McCarty, Head of Investor Relations. Please go ahead, Traci. Thank you very much, operator, and thank you all for joining us today to talk about Roctavian approval in Europe. On the call from BioMarin's management team are JJ Bienaimé, Chairman and Chief Executive Officer, Jeff Ajer, Chief Commercial Officer, Hank Fuchs, President, Worldwide R&D, and Brian Mueller, our Chief Financial Officer. To remind you, this non-confidential presentation contains forward-looking statements about Roctavian and the business prospects of BioMarin Pharmaceutical, Inc., including expectations regarding BioMarin's financial performance and the clinical development and potential regulatory approval of Roctavian and other commercial products and products in development. Results may differ materially depending on the timing and nature of decisions by regulatory authorities, the progress of BioMarin's development programs, BioMarin's ability to successfully commercialize Roctavian and other products, developments in the pharmaceutical industry, actions by competitors, and those factors detailed in the press release we issued today, as well as BioMarin's filings with the SEC such as 10-Q, 10-K, and 8-K reports. Now, I'd like to turn the call over to our Chairman and CEO, JJ Bienaimé. Thank you, Traci, and good afternoon, or evening, and thank you all for joining us to discuss today's European approval of Roctavian. Roctavian is the first approved gene therapy product for the treatment of adults with severe hemophilia A. I wanna thank all the people who participated in our clinical programs, our investigators and advocates, and our BioMarin colleagues who worked to bring this groundbreaking new treatment to people with hemophilia A. Today's news marks a significant milestone for the scientific community, many of whom have contributed over the last three decades to this momentous approval. For BioMarin, the perseverance demonstrated by our R&D organization over the last seven years is emblematic of how we get things done on behalf of the patients we serve. While BioMarin is known as a power-pioneering innovator, we now have 8 novel commercial products which on the market. Today's achievement is a high watermark for our organization and for scientific innovation across our industry. For our shareholders, we share today's accomplishments, and we thank you for your support throughout our journey to bring the next generation of innovative therapies to the hemophilia A community. This approval from the European Commission unlocks Roctavian access to thousands of people with severe hemophilia A in 24 European countries within BioMarin's commercial footprint and is a first step to facilitating access to main patient sales markets in the Middle East. We were also very pleased to have maintained orphan drug designation in the EU, providing ten years of market exclusivity, underscoring the significant benefit Roctavian has over existing therapies for patients with severe hemophilia A, as assessed by the European community. We extend our appreciation to the EMA for their acknowledgment of the groundbreaking nature of Roctavian gene therapy for the benefit of the hemophilia community. Thank you for your commitment to BioMarin as we have persevered through our global clinical development programs and regulatory procedures, as well as invested in our world-class gene therapy manufacturing facilities in preparation for this day. We are pleased to have ample supply of our Roctavian ready for labeling and distribution to our key treatment centers in Germany. As we anticipated today's news when we received this positive CHMP opinion in late June. We are ready to launch. I will now turn the call over to Jeff, who joins us from Japan, where we are celebrating the launch of Voxzogo, to describe now our Roctavian launch plans and our product readiness and the reimbursement outlook and market opportunity for Voxzogo in Europe and the Middle East. Jeff? Thank you, JJ, and good evening, everyone. Suffice it to say, we have been preparing for this day for a few years, and the commercial team is ready to launch Roctavian in Europe. Before I begin, I would also like to extend our gratitude to the families, colleagues, investigators, and European health authorities who have all contributed to this first approval of any gene therapy for treatment of severe hemophilia A, a significant achievement on behalf of the hemophilia community. Turning briefly to some label highlights. Roctavian is indicated for the treatment of severe hemophilia A in adult patients without a history of Factor VIII inhibitors and without detectable antibodies to adenovirus, Adeno-Associated Virus serotype 5 or AAV5. Roctavian is contraindicated in patients with active infections, either acute or uncontrolled chronic, or patients with known significant hepatic fibrosis or cirrhosis. The recommended dose of Roctavian is 6 × 10^13 vector genomes per kilogram body weight, administered as a single intravenous infusion. Prior to the administration of Roctavian, recipients will provide baseline measurements of liver health. In the first year after Roctavian administration, liver function and Factor VIII monitoring will be conducted to determine the need to initiate a course of corticosteroids on an on-demand basis. Should ALT levels rise above the upper limit of normal or 1.5x baseline and consistent with the protocol outlined in our phase III program. Other safety items included in the label reflect our clinical trial experience and as expected, includes information related to managing liver health, guidelines regarding the use of corticosteroids, infusion-related reactions, the risk of thrombotic events, and the risk of malignancy as a result of vector integration. Additional safety information is described in the product information, which will be posted to the EMA website in the coming days. Additionally, as part of our commitment to substantiate the long-term efficacy and safety of this gene therapy, patients are expected to be enrolled in a registry designed to follow patients for 15 years, as agreed with EMA and in line with EMA guidelines. Now on to European launch plans. Today's approval unlocks access to Roctavian to thousands of people in the 24 countries within BioMarin's European footprint. We anticipate additional access to Roctavian for patients outside of the EU through named patient sales based on the EMA approval in countries in the Middle East, Africa, Latin America, and expect additional market registrations to be facilitated by the EMA license. Turning to pricing and reimbursement anticipated in Europe. As we have said previously, we anticipate the price of Roctavian to reflect the improved clinical outcomes demonstrated across our studies as compared to standard of care. Payers already understand what it costs to provide chronic care to people with severe hemophilia A, so the value proposition demonstrated by Roctavian offers the potential for significant cost savings to healthcare systems. Only six of 134 participants in our phase III study resumed treatment on standard of care prophylaxis, and we are very enthusiastic about the prospect of a one-time treatment option with such high responder rates. Acknowledging that a one-time durable treatment like Roctavian will come with a substantial cost up front, we have been working with payers for years in preparation for this day. We have taken the approach that different payer systems have different needs, so we plan to customize outcomes-based agreements market by market. We expect these outcomes-based agreements, or OBAs, will cover the risk of a non-response over a period of many years and are targeting five-eight-year agreements in Europe. As we have said previously, we've been in discussions with health authorities and health insurance organizations in our initial market, Germany. Our discussions have resulted in a framework for outcomes-based payment models. We are in the process of finalizing those agreements, which we expect will facilitate commercial treatment with first patients of Roctavian in the fourth quarter. In France, we submitted for early access for Roctavian and expect that review to begin imminently. Turning to the launch cascade in Europe, we plan to launch Roctavian immediately in Germany, where we will have first year free pricing, and Germany is the largest European market for severe hemophilia A. We anticipate the one-time price in Europe to be around EUR 1.5 million for a one-time treatment with Roctavian, net of all discounts and reserves. We expect to share the European list price with you in October, and we anticipate that this price will be in line with, but lower than the comparable U.S. net price. Our next market will be France, which is also significant in size and has an early access program which we plan to leverage while we go in parallel through the full price and reimbursement process, which can take about a year in France. We expect to pursue pricing and reimbursement in Italy and Spain, the latter also having a named patient sales channel that may be available to us while we pursue full pricing and reimbursement in Spain. Beyond these initial markets across the EU4, we anticipate other named patient sales opportunities in Europe, the Middle East that key off of today's approval. We do anticipate some pent-up demand will drive initial sales in the fourth quarter of this year and expect an increasing uptake of volume beginning in the first quarter of next year. In summary, the commercial team has been preparing for this day for years. We are so pleased to have the breadth of data on which today's approval was based and the transformational impact of Roctavian demonstrating a reduction in annualized bleeding rates and factor use unmatched by any available therapy to date is an important breakthrough for patients. We've been very pleased with the growing body of market research illuminating both awareness and interest in treatment with Roctavian. Recent market research indicates that with healthcare professionals Roctavian could capture approximately 35% of eligible patients and in line with our expectations. We were pleased to see that approximately 80% of healthcare professionals surveyed expect to treat at least one patient with Roctavian within 12 months of approval. Based on the strength of Roctavian data and the encouraging market feedback on interest in treating, the commercial organization is excited to get started on European launch today. On our next quarterly call, we expect to share metrics that will help you follow the cadence of Roctavian uptake in Europe. Thank you for your attention, and we will now open the call to your questions. Operator? If you would like to ask a question, please press star one on your telephone keypad now. You'll be placed into the queue in the order received. Please be prepared to ask your question when prompted. Once again, to ask a question, please press star one now. Our first question comes from Chris Raymond from Piper Sandler. Please state your question. Hey, thanks, and congrats guys, again, for all the perseverance and the success here. Really great to see. Just a couple questions if I could. You know, Jeff, just on the net price with discounts and reserves, can you maybe verify what that assumed sort of non-responder rate is? I think you mentioned six of 134 patients in your trials, but is that what's baked into that? Is that the ratio that we should be thinking about? Maybe can you tell us what the gross price is? What's the list on that? Then I got a follow-up. Thanks, Chris. You know, I might defer to Brian Mueller on the question of the discounts and reserves piece. Yeah, thanks. Thanks, Jeff. Thanks, Chris, for the question. This is Brian. You're not far off. As you can imagine, we're planning to use the totality of our clinical data, both the two-year, soon-to-be three-year phase III data of 134 patients and now six years of data from the Phase I/II study. While we've reported the key clinical outcomes from that data, that is the same set and the same data we'll be looking at as we form these estimates. When you think about responder rates, that six out of 134 is a good place to anchor to. On the gross price? On the subject of gross price, we don't have a gross price listed yet, Chris. We will be submitting that first in Germany, so it needs to be submitted on a twice-a-month cadence, and then it takes about a half a month for that price to be listed. We'll be finalizing that, and that'll be listing in the next month or so. You know, we normally guide to expectations of net revenue per patient so that you don't get tripped up on a gross to net having to come up with a gross to net assumption. I would guide to home in on that estimated EUR 1.5 million per patient net. Great. Thanks. Maybe just a quick follow-up. You know, some of our checks uncovered recently a number of centers had you know active patient registries. I know you probably don't want to give a number here of patients, but maybe can you just put some brackets around, especially in Germany and France, maybe the you know sort of range of or you know ratio of target centers that actually have active registries that are in place for Roctavian? When you say registries, I think you mean some kind of a waiting list of patients that are interested at a particular center. I got that right? Yeah, that's right. Yep, that's right. Yeah. Well, we have seen signals of that since the CHMP positive opinion at the end of June. I don't have a full accounting, you know, center by center, country by country. What I would say is it's a very encouraging signal of demand that these lists of early adopters are starting to form at probably early adopter centers. Those are important, great signal of demand. We'll be targeting those first. I will note that, you know, a signal of demand like that is really important. It is subject to, first, having a reimbursement approval for those patients to get treated under, and second, the mechanics of doing the workup of the patient like I described, checking for liver health, making sure that they are AAV 5 seronegative, making sure the center has gone through an onboarding process and they're ready to treat patients. So there are some important mechanics early on, especially that will gate those patient registries, as you're calling them. Great. Thank you. Our next question comes from Salveen Richter from Goldman Sachs. Please state your question. Good afternoon and congratulations. Maybe two questions for me. One is on, could you just remind us on the cadence of the launch across Europe and when these various countries on board? Help us understand who the early adopters are in each of these countries. Jeff? All right. The cadence of launch, I've described on a number of occasions and in the script. The first market is going to be Germany. Germany is both the largest market in Europe for severe hemophilia A, and it's the one place in Europe where we have a free pricing period. We'll be targeting Germany first. The second most important market in Europe is France. As I've described, there's an early access program that we've already submitted to in France and for which the review will begin imminently with this approval. France will be second. The balance of the so-called EU 4, those are the four most important markets in Europe, are Italy and Spain. We'll be targeting Italy and Spain to follow Germany and France. Beyond that, we'll be taking advantage of early access and name patient sales opportunities in markets where they present themselves. To that end, you can think about some of the small numbers of patients we've reported being treated with Voxzogo in some of those markets. We'll be pursuing similar opportunities. Also in key markets in the Middle East and Africa, these would be markets such as Saudi Arabia, Kuwait, the UAE, and even Argentina and Latin America, where we've had success with early access sales following a major market approval like we've just received today. That would be the initial cadence. Like we have with other launches, we will likely be reporting new active markets each quarter so that you can follow along with that cadence of launch. Our next question comes from Geoff Meacham from Bank of America. Please state your question. Hi, this is Charlie Young for Jeff Meacham. Congrats on the approval. Maybe I have kind of two questions. The first question is, I think you mentioned about that you're going through the assessment period with France, and that may take about a year or so. I guess following the launch sequence, I guess, how should we think about the actual kind of revenue from the recognition standpoint? And then I guess on the second question is, in terms of the FDA, I think that's kind of where people are kind of focusing right now in terms of the resubmission study. I'm just wondering if there are any more granularity that you could provide beyond the end of the September submission timeframe, in terms of kind of discussion behind the doors? Thank you. Jeff, why don't you answer the first question and, Hank, maybe you can answer the second one. Okay. I think you were the question was how to think about recognition of revenue. I'll ask Brian to keep me honest if I miss anything here, but in general, we expect the revenue to be recognized at the time of treatment. We're selling actual vials of product, and like with our other products, when we transfer those vials to the end user, that's when we will be recognizing the revenue. That'll be essentially a revenue up front. That revenue up front that we're recording will be net of actual and anticipated discounts and reserves under an outcomes-based agreement. Yeah. Thanks, Jeff. This is Brian. Maybe just to elaborate a little bit, because I heard in the question an aspect about the pricing and negotiation period and process in France and then the early access program. The question may have been about clawbacks or rebates once a final price is determined. That's done at the country-by-country level. In certain countries, there's this repricing where while the final price might be different or lower, there would not be a rebate. In countries where there might be a clawback of revenue or reimbursement during the negotiation phase, we actually have experience with this in our other products, and we're usually able to estimate what that amount may be, and we would reserve that as part of our gross to net, and you wouldn't see it in net revenue. Again, we've got experience with other products doing that. What we would not expect to be in a situation which perhaps we've seen elsewhere, where you're required to defer revenue during that period waiting for that final price. We wouldn't be in that scenario. Hank, you want to comment on the U.S. filing? Yeah. You asked if there's any additional granularity. Sort of not really. I mean, the main news since the last time we've spoken to you about U.S. plans is the European Commission's authorization of the marketing application for Europe. While that may not directly read through on the FDA, it's certainly better than the alternative. As regards the other activities for the FDA, you know, we have this interaction with them, fairly detailed, and we're on track for delivering everything they've asked for. We believe that the information that we have will address the questions that they've raised. Thank you. Our next question comes from Gina Wang from Barclays. Please state your question. Hi. Thank you for taking our questions. This is Xin Wang for Gina Wang. Congratulations on the approval. My first question is about your outcome-based payment. What are some of the criteria that determine the payback? How do you define the failure? Any specific quantitative metrics we can follow, like how many events, bleeding events reported, or based on patient or based on physician determined? How much do you need to pay back? Will it be a binary like 100% once the event happens, or a percentage based on the number of events that happened to a patient? I'll field that question. I think we have covered some of that, but Jeff, you want to reiterate. Yeah. We have covered that on multiple occasions. In terms of the criteria for the Outcomes-Based Agreement, essentially we're guaranteeing that patients will respond initially and then be not bleeding and free from prophylaxis therapy for the period of time of the agreement. In very simple terms, and I don't think you need to be more complicated than this, think about it as first initial response and then continued durability as measured by not having to return to prophylaxis during the guarantee period. As we've discussed previously, how that would work in practice in most anticipated agreements would be something like if you had a five-year agreement period and you had a patient that returned to prophylaxis after four of those five years, then we would have... The payer would have captured 80% of the value for four of five years. 80% of the value of the term of the agreement, and we would rebate back 20% in that simple example. Thank you. I think Brian explained, however, based on the clinical data we have so far, we can pretty clearly, you know, establish the percentage of patients that are anticipated to go back to prophylactic therapy, at this time. This will be part of a reserve that will be taken up front from the gross price of Roctavian. As we explained, again, the anticipated initial price in Germany will be around EUR 1.5 million, net of all discounts and net of all outcome-based agreement reserves. If the patient fails, as in Jeff Ajer's example, the patient returns to prophylactic therapy at year four in a five-year agreement, we'll pay 100% of the cost of the therapy in the fifth year, you know, from year four to five for that patient. I think maybe you're referring to another company that has a recent approval, ex vivo gene therapy, where I think they said they would cover 80% of the cost. We are covering 100%. Okay. Thanks for your clarification. Thank you. Of course. Also you mentioned there will be the agreement in different new country, countries would be between like five-eight years. This kind of payback will also based on that period. Is that correct? Yes. I mean, Jeff or Brian, do you want to answer that one too? Yeah. We're targeting. I'll jump in there. Go ahead. No, I was gonna say yes. Targeting five-eight, these agreements will still be, you know, still being negotiated and as we enter the country-by-country launches. You could model or envision a proportionate value arrangement. Whether it's five or eight that the value of the financial protection that our outcomes-based agreement would provide would be proportional to the timeframe of durability in the outcomes-based agreement. If I may add also, all this is going to be based on the fact that we have now six years of efficacy data on bleeding control available with our phase two trial. We're gonna have seven years in mid-June of next year. I think we're using that data to guide the reserve we're gonna be taking upfront from the upfront cost. Okay. Thank you. May I add follow up with one more question about the price? Based on your interaction with German payers, about your $1.5 million net price, have they, like, is this price they have agreed upon or have they commented or have any feedback on your price? Jeff? Because as I've noted, I said we are working to finalize those agreements. They haven't been finalized yet, but that's our target for where we think we're gonna wind up. Okay. Thank you. Congratulations again. Our next question comes from Robyn Karnauskas from Truist Securities. Please state your question. Hi. Thank you all. I do want to say congratulations to not just the senior members, but I mean, a lot of people worked on this. I've followed you all for a while, and I think manufacturing all the way up. Congrats. It's a big deal for hemophilia patients. I have two questions. I guess, JJ, you've talked a lot about the value proposition being more than $1.5 million. I guess, I know that's the net price. Can you help us understand how you think, you know, payers think of. When you chose the $1.5 million, are you talking about the $1.5 million net? You're obviously saving a lot more to the system than that. Talk to me about, you know, how your thought process and the negotiations or your thought process about that price point. The second question is, you know, with conditional, it's the wrong CMA, so you're having an approval which requires you to submit more information. In other indications that are a lot more broad, not orphan drugs, sometimes European nations push back on reimbursing those. Explain to us, with conditional approvals like that, how confident you are that upfront reimbursement will occur in Europe. Thanks. Actually, these two questions. Thanks, Robyn. These two questions are linked because the fact that we have an outcome-based agreement where we guarantee success here kind of you know reduces the risk of reimbursement for conditional approval. Although Jeff has looked at that in detail and is going to provide his comments. The EUR 1.5 million, again, anticipated is net not only of the usual discount but net of our outcome-based agreement anticipated reserve. This is the European price we're talking about here, not the U.S. price. We have talked about in the past, and we are firm on this about, you know, a higher U.S. price, but it's not gonna be double the European price. It's the fact that we have to take into account in Europe the fact that the cost of hemophilia therapy with existing product is lower than in the U.S., and consequently, we need to adjust for the cost offset in Europe that's gonna be a little lower than in the U.S. This is why, you know, we end up with around EUR 1.5 million net of reserves and of discounts and reserves for the outcomes-based agreement. Jeff, you wanna talk about the conditional approval and reimbursement where we think it's not going to be an issue. Thank you, JJ, and thanks, Robyn, for the question. We don't think that the conditional marketing authorization is going to be an issue here. The nature of the approval is less important than the data that we have to support the product and also the terms of the outcomes-based agreement, as JJ noted. Relative to your question of, you know, analogs, I would say when you look at those analogs that haven't done well in Europe following a conditional marketing authorization, it's likely that their performance is related to the data and the outcomes that they have behind their product and not the nature of the approval itself. Back just briefly to the notion of value proposition. The value proposition of Roctavian goes well beyond the cost offsets relative to not having to pay for prophylaxis therapy for a period of likely many years. However, the European system ties reimbursement prices back to and anchors to the cost of standard of care therapy. I will note that the standard of care therapy prophylaxis in Europe is lower than it is in the United States. Awesome. One follow-up question, financial question. When we think about margins, like now that you have this net price, how do we think about then to advocate towards getting more patients in the office in Europe and getting them seen and support for doctors learning a new therapy? How do we think about margins in near term in the beginning of launch? That's my final question. Thank you. Brian, you wanna go over that? Yeah. Thanks. Thanks, Robyn. We're excited to actually be launching Roctavian in Europe. As Jeff noted, we've been planning and anticipating this for a couple of years now, and that means building the launch capabilities. Important to note first, operationally, Roctavian will plug into the same global infrastructure that supports our roughly $2 billion of annual revenues today. This includes supply chain, core commercial capabilities such as market access, medical support as you noted, and then, you know, global corporate commercial support, as well as G&A. But with that being said, we're entering a large and competitive hemophilia A market. We plan to make and need to make incremental investments in Roctavian in order to maximize its launch success. While we will have those additional investments and sales and marketing and SG&A overall will increase on an absolute dollar basis because of the leverage that we're getting from the existing business, we anticipate that our this fits into the margin improvement story that we've been discussing for the last year or two. You'll see investments increase, but we would still expect that overall sales and marketing over time, especially as Roctavian revenues grow, will decrease, therefore, increasing operating margin. Robyn, maybe Brian, maybe I think, maybe I'm wrong, but I think maybe Robyn was interested in gross margin also. Is that correct? Was that what you were after, Robyn, or just operating margin in general? I think both. I mean, that, you know, that's great color. I think we both are asking the question whether or not you'd need more expenses on the bottom line. Also I think gross margin too, given the net price is EUR 1.5, where we, none of us know what the real price of the therapy is. It's harder or the cost of the therapy is as well. Any color you can give. It sounds like you'll fit into your guidance, so none of us have to worry about expenses, but maybe give color on the cost as well. Yeah. Thanks. First of all, on that last piece, yes, because we were anticipating this launch in Europe, we have included the necessary or planned SG&A investments within guidance. On gross margin, you know, Roctavian as being a gene therapy, you know, made in our 35 [inaudible] plant in Novato, is a dedicated state-of-the-art gene therapy plant. Inherently, the cost to manufacture Roctavian, you know, is significant. Each patient cost will be significant. However, as you noted, because of the upfront revenue recognition, because of the planned single price for a single dose of Roctavian, and the high price, we do anticipate that Roctavian gross margins will be higher than our base business, which hover around the high 70%. About a 22% cost of goods sold. Roctavian, we anticipate, will be in the lower teens%. I mean, lower teens in terms of cost of goods, not gross margin. Yeah, cost of goods. Over time, as Roctavian becomes a substantial contributor to our total revenues, likewise for Voxzogo, which has higher gross margins than our base business, this again fits into the overall margin improvement strategy for the company. Great. Thank you, guys. Congrats to everyone below you who have actually worked really hard. Congratulations to you as well. Thank you. Our next question comes from Matthew Harrison from Morgan Stanley. Please state your question. Great. Good evening. Thanks for taking the question. I guess two for me. So one, can you just give us some sense of, especially for Germany and France, what you see as the relative size of those local markets? And then, you know, given it sounds like the survey work that you've done, who do you think are gonna be the initial types of patients, or what is the initial patient going to look like, in terms of launch? Thank you. Hi, Matt. You know, Germany and France are the largest markets in Europe based on a number of measures, but one of them being you know, population size. I would say relative to our overall guidance of the total number of severe hemophilia A adults that are within the set of EMA markets, and the EMA markets are the EU 28+ Liechtenstein, Norway, and Iceland. Think about Germany and France as being proportionate to the total. We reported about 8,000 severe adult hemophilia A patients. Think about Germany and France being proportional on a population basis. Similarly for the estimated, I think 3,200 patients that we said would be eligible based on the initial label, which we also described, think about proportionality there. By the way, a comment on that initial label. As we reported, we have lifecycle management plans and studies that are underway that would help us expand beyond that initial indication over time. In terms of the survey work. I mean, France should be around 75%. France should be around 75% of the German market based on the relative populations, about, you know, 84 million German people and 65 million French people. It's gonna be proportional. In terms of the survey work and initial adopters, I'm sure you can appreciate, for competitive reasons, we're not gonna give you a profile of our initial target patient population. Importantly, we think that all patients, including patients on prophylaxis with Factor VIII or Hemlibra, or even patients that are not on prophylaxis are and can be eligible for treatment with Roctavian. We have given you guidance in the past that, you know, our survey indicates that Factor VIII patients in particular that are not performing well on Factor VIII prophylaxis have been particularly interested in Roctavian. Also Hemlibra patients that may be doing well on Hemlibra but are demanding a higher performance of their treatment could be initial targets as well. Thank you. Our next question comes from Tim Lugo from William Blair. Please state your question. Mr. Lugo, are you on the line? Maybe you have your phone on mute. I am on the line, and yes, I was on mute. I just wanted to pass along my congratulations to the whole company as well as the patients. I know it's a major day for everyone. Can you maybe discuss the ODE and how that- You know, how you feel that enabled exclusivity. I assume other, you know, factor gene therapy programs, you know, are also watching today as a major event. Can you just talk about, you know, how if you expect to be the only gene therapy available in the EU during the duration of that ODE? Maybe I'll start, and Hank can provide his perspective. I think the value in addition to the market exclusivity of this orphan drug, you know, extension here, it just illustrates the fact that the European Commission after reviewing our medical file believes that Roctavian is a major improvement compared to existing therapies, including recent launches. Hank, you wanna talk about exclusivity and. Yeah, I think the specific rules on exclusivity pertaining to similarity of products have been generally but not sufficiently specifically outlined to be able to predict what impact any of this might have on any of the followers. I'd also say that, you know, it'll be a lot of years before this even comes to the fore because those followers are still far behind BioMarin. I think that, as JJ said, the major element of the orphan designation from a development perspective is simply the recognition that it has the potential to offer a potentially superior therapeutic outcome for patients with unmet medical needs. You know, for over and above available therapies. Understand. Thank you. Congratulations. Mm-hmm. Our next question comes from Paul Matteis from Stifel Financial Corp. Please state your question. Hi, this is James on for Paul. Thanks for taking our question. Just wanted to confirm quickly, there's no black box warning or anything for oncogenesis risk, correct? It'd just be helpful to get some color on kind of how that's characterized. Then secondly, just based on kind of steroid directions on the label, I guess, how are you thinking about what percent of patients will ultimately need steroids and I guess for how long on average? Thanks so much. Hank? Yeah. The label talks about. Well, first of all, the label will be available in several days. From what we understand about what will be finalized in the label, the label does mention vector integration as a potential consideration, but acknowledges that as of the writing of the label, no AAV therapy has been associated with cancer causation. Then on the issue of corticosteroids, we expect probably 80% of patients will take corticosteroids, and there's a lighter tapering regimen on the back end. We expect that, I think by and large, most patients will be done within six months of initiation of steroid therapy. They won't be on, you know, very high doses, and they won't be on even moderate doses for very long. We had a very good dialogue with the EMA about what we learned in the clinical trial, and they concluded as we did, that more is not necessarily better. If I may, Hank will explain that actually there's no such thing as a black box in European labels like that. It's a U.S.- Yeah. We didn't get one either. We didn't get one, but generally they don't really have black boxes in Europe. Great. Thank you. Our next question comes from Divya Rao from TD Cowen. Please state your question. Hi. Good evening. This is Divya on for Phil. I would like to add my congratulations on the approval. I have two questions. Divya, you're there. I have two questions. Yeah. Can you guys hear me? Yes. Yes. Okay. My first question is, could you provide any color on like specific metrics we can expect on the launch, in the next few earnings calls? I know that earlier you mentioned that you plan to provide number of active markets, but are there any other metrics that we can expect on the call? Then the second question is, with achondroplasia, you previously noted that the model of care in France and Germany are slightly more concentrated, whereas, compared to the model of care in the U.S. Do you see a similar dynamic with Roctavian's target population as well? I'll start with your first question and let Jeff answer the second one. Yeah, we will be providing the metrics that we anticipate to communicate to you on a regular basis when we have our Q3 conference call in October. Since at that time, the product will just have been started to be shipping in Europe, you know, just two-three weeks earlier. We'll let you know what we anticipate to communicate on a going forward basis in terms of key launch metrics. Jeff, second question. Yeah. On the question of concentration of care model in Europe, that's exactly the case, and there is a direct analogy between achondroplasia and hemophilia, particularly in the initial markets of France and Germany. In France and Germany, there are both hemophilia treatment centers that are readily identified where patients are treated and also comprehensive care centers, which you could think about as being particularly well-equipped, well-resourced and sophisticated hemophilia treatment centers. Importantly, the hemophilia community in Europe has published a couple of journal articles in the journal Hemophilia. We can follow up with specific references in both 2020 and 2021 describing the intention of treating hemophilia patients with gene therapies through a so-called hub and spoke model. The intention is that the hubs would largely be the hemophilia treatment centers around the country, and they would be referring patients into a small or a relatively smaller number of their peers that are likely to be comprehensive care centers for actual treatment with Roctavian and other gene therapies potentially. Those patients would be referred back to their spoke hemophilia treatment centers for monitoring and follow-up. That's the model that we're expecting and working to in conjunction with the hemophilia community. That's their model, not ours. We're just following along with that. Yeah. That's helpful. Thank you so much. Our next question comes from Luca Issi from RBC Capital Markets. Please state your question. Oh, great. Thanks so much for taking my questions again. Congrats on a great approval here in the EU. Maybe a quick one on, if I may, U.S. pricing. What's the latest thinking there? I think in the past you have implied that the EU was going to be priced, I think at a 30% discount versus the US. Is that still the case? Is it fair for us to assume the net price in the U.S. will be $2.1 million-$2.2 million? And then maybe on the steroid study, can you remind us when the steroid study will read out? And maybe related to it, how should we think about a potential risk that the FDA will want to wait for that data before you can file the BLA? Thanks so much. Jeff, will you answer your first question and, Hank, you take on the second one on the BLA? Yeah, happy to. I think what we've guided to on European versus U.S. pricing expectation is that Europe would be lower than, but relatively or somewhat lower than the U.S. price net, but in line with. I think if you look at what we're guiding to today to a target net price per patient in Europe of about EUR 1.5 million, at least starting out with the initial markets, and you think about how that compares to JJ's previous guidance on U.S. pricing, which has been probably not lower than $2 million, probably not higher than $3 million. You account for the standard US gross to net discount up to and including an expectation that most, if not all, patients in the U.S. would be eligible for 340B discounting, which would be part of our gross to net calculation. You can see, without being overly specific, that generally that EUR 1.5 million per patient would tie up to, you know, kind of the guidance of somewhat lower but relatively in line with our expectations also for the U.S. We haven't set a price for the U.S. market, and we won't until we get an approval and we'll advise at that time. Thanks. On the studies and filings. Yeah. You know, we've had dialogue with the agency about the requirements for filing and they're not waiting for the Study 270-303 that's fully enrolled and for which the first data readout will occur at the beginning of the year. I think today's news is that a health authority, a major health authority in the world, has decided that the availability of the therapy, given the unmet need and available alternative therapies, warrants expediting asset availability of Roctavian to address the public health need represented by severe hemophilia. I think that again, the read-through is not direct from EU to U.S., but I think it puts a positive light on the potential for another for the U.S. health authority to take a similar decision. Got it. Thanks so much, guys. We are out of time. Thank you for joining us. I'll turn the call back over to Jean-Jacques Bienaimé for closing remarks. Yes, thank you all for joining us today to obviously mark this significant moment for people with severe hemophilia A for the field of gene therapy in general and the good work of the team here at BioMarin. As pioneers in the field of transformative medicines, we are so pleased by this tremendous achievement. Thank you all for your support, and we look forward to talking or seeing you soon. Goodbye. This now concludes today's conference call. Thank you for attending.