Great. Good morning, everyone. Welcome. My name is Jessica Fye. I'm a large cap biotech analyst at JP Morgan, and we're delighted to be continuing the conference with BioMarin this morning. Good news, we're not gonna switch rooms for Q&A today. There's gonna be mic runners. If you have a question after the presentation, you can raise your hand, someone will bring you a mic. You can also submit your questions electronically, and I can ask them. Without further ado, let me pass it over to the company CEO, Jean-Jacques Bienaimé. Thank you, Jess. Good morning, everybody. It's a pleasure to be back here in person after this COVID hiatus. As usual, this presentation will contain forward-looking statements. Please refer to our 10-K and 10-Q filings. Again, it's good to be back. As you know, you know, BioMarin is really anchored in science, and I would say all the genetic products breakthrough that we've been developing and launching are foundational to our performance. In a nutshell, we believe we are a best-in-class genetic disease company. We believe we're at inflection point of transformative growth. We have a base business, you know, enzyme business that is pretty solid, profitable and still growing. Also protected from IRA regulations because our Medicare business is very small. Also our products are very complex and expensive to manufacture. They are true biologics, consequently, the barriers to entry are very high. You know, generally the average biopharma product peaks nine years after introduction. You know, Aldurazyme, Naglazyme are 17 and 20 years old product, they're still growing. We have a very solid base business that will continue to grow in the single digits every year. The key thing here is that as we know, we launched Voxzogo last year, which is doing very well as a first treatment for achondroplasia. This is our strongest launch to date. Now Roctavian was approved late last year in Europe for severe hemophilia A gene therapy. We are looking forward to approve in the U.S. by the middle of this year. As you will see, our profit margin is expanding thanks to this new revenues. We're gonna, you know, leverage our world-class infrastructure we've been building over the past 10 years. We also believe that we have best-in-class innovation capabilities with, you know, industry-leading R&D teams. The company has now eight internally developed genetic-based commercial therapies on the market. We are definitely fully integrated and scaled up in terms of discovery, clinical, regulatory, reimbursement, worldwide manufacturing. And we are just gonna continue to leverage all the advances in genetics to continue expansion of the company between now and 25 and beyond. Here is where we start. A recap. In Q3, we had a pretty significant growth year. 12% growth in revenues year to date at the end of September of last year. 17% with our KUVAN, which is generic now in the U.S. Very significant operating margin expansion from -1.2% to 11.2%. Our GAAP net income is now positive. This is gonna be 2022, the first time in the history of the company without any special event that we're gonna be GAAP profitable. We intend to continue to be GAAP profitable on a going forward basis. As shown on this slide, I'm kind of pre-announcing a little bit on the left the 2022 revenues, which were around, which will be around $2.09 billion, almost $2.1 billion. We anticipate those revenues to actually double or so by the mid-decade to $4 billion-$5 billion, thanks to the maintenance of our, you know, base products and the slow growth of our base products, then the continued expansion of Voxzogo and the launch of ROCTAVIAN. Our strategic priorities are to from now on drive sustainable growth and value creation and sustainable profit growth and profitability. If you look at, you know, between now and between 2018 and 2021, again, we had. In terms of our core products, our enzymes, many of our enzymes, as you see on the slide here on the right, Vimizim, Naglazyme, Bonvizin, Brineura, and Aldurazyme, these are all proteins. They're all enzymes. They've been growing on a compound annual growth rate of around 14% between 2018 and 2021, they're gonna continue to grow, as I said, in the future. Obviously, the key driver of growth is gonna be in the short term VOXZOGO and ROCTAVIAN, starting with VOXZOGO. As you saw last week, we announced that we filed for expansion of our label to patients under five years of age in the U.S., under two years of age in Europe. You see on this slide, right now we got about 17,000 market, eligible market. We're gonna move to 18,000 with approval, hopefully at the end of this year. Which is a in terms of market size, about a $3 billion market opportunity. We have now passed, at the end of last year, we passed 1,000 children treated with Voxzogo. We are active in 32 markets. Are pre-announcing here also our 2022 revenues, which were about $169 million. We are very comfortable with the consensus sales for Voxzogo in 2023. Based on that, actually, if you annualize our December sales, we are basically on a run rate already of $300 million a year with Voxzogo. Very successful launch, and we are very excited about the label expansion and the future growth. Now moving to ROCTAVIAN. This is a slide that's showing the market size initial, based on the initial label, or anticipated label in the U.S. About 3,000 patients in the EMA, 3,000 in the U.S., rest of the world about 7,000. That's 13,000 patients or so initially for eligible for ROCTAVIAN treatment, about a $14 billion plus market. We should be treating our first patient this quarter in Germany, and then Italy, France, will be coming in the second half of the year. The U.S. hopefully, by the middle of the year, Japan, Brazil, which will be pretty important, markets too by the middle of decade. I just wanna emphasize here that we do believe that ROCTAVIAN is absolutely a transformational product and has a major impact on the quality of life of severe hemophilia A patient. This is a quote from a one of our European patients that has been treated a few years ago in our clinical trials. It says, "The impact of gene therapy on my day-to-day has been a life change. It has been a big change, and it's with a peace of mind of living day to day without being afraid of everything. That is the three years that I've had so far a normal life, not bleeding, not even once." Again, on the commercial outlook, again, we announced in the press release yesterday that we signed our first outcome-based agreement in Germany. leting additional outcome-based agreements with large insurance sick funds in Germany this quarter. Testing with companion diagnostic is already underway for some patients. We expect to treat our first German patients definitely this quarter, if not this month. We are comfortable with the ROCTAVIAN full year 2023 consensus estimates, assuming a late March approval in the U.S. We will provide full 2023 ROCTAVIAN guidance when we report our Q4 2022 in February. The interest in ROCTAVIAN is still the same from healthcare professionals in Europe and the U.S., based on marketing research we did last year 80% of healthcare professional in Europe are likely to adopt ROCTAVIAN within one year availability, and they think that ROCTAVIAN will capture 35% of the entire severe adult hemophilia patients in Europe, 75% in the U.S., and 40% market share anticipated for severe adult hemophilia A patients in the U.S. Also in the U.S., we're making great progress. As you know, ICER did a cost-effective analysis over one year ago, Last December, a few weeks ago, they published their final assessment, whereby they determined that ROCTAVIAN is cost-effective in the U.S. at around $2.5 million per treatment, which is very good for us. We have already been approached by several large US health insurance companies. It was inbound calls. They called us because they want to implement a favorable policy for ROCTAVIAN reimbursement in the U.S. We believe that, you know, we're gonna have some US outcome-based agreements in place in the form of a warranty, guarantee of efficacy with ROCTAVIAN over several years. The FDA completed our pre-license inspection of our gene therapy facility, which is 45 minutes north of here in Novato. They did that in December. We had a few comments from the agencies and observations. We believe they are addressable. Actually, we have already answered their comments, and we are preparing for launch. The FDA has also planned some clinical site inspection that will take place this quarter before the PDUFA date. As, as we had communicated earlier, we are going to submit the three-year phase III data to the FDA in the coming weeks. With this, one of our, you know, strategic priority is aggressive lifecycle management of our existing products. Starting with VOXZOGO, right now, achondroplasia, addressable achondroplasia market opportunity is around 18,000 patients in BioMarin territory. It excludes India, China, and most of Sub-Saharan Africa. As you know, we had a investigative sponsored trial that shows that VOXZOGO is likely to be effective in other genetic form of short statures. We actually have identified a few indications where it looks like VOXZOGO vosoritide is gonna be effective, like hypochondroplasia. They are listed on this slide here. Actually, we've done some marketing research. If you look at those different markets, there are about 600,000 patients between the age of four and 17 that could be eligible for treatment with vosoritide that are more than three standard deviation below average, which mean that they are, you know, severely impacted by the disease and could be interested in treatment with VOXZOGO. We have plans to actually start some studies to explore those new indications. Now, on ROCTAVIAN, initially, I said earlier our initial indication, initial market is about $14 billion. We have several clinical studies already started to expand the market eligibility. First one on the slide is, you know, patients with prior factor VIII inhibitors, so that would add another $4 billion to addressable market. Patients with active inhibitors, another $2 billion-$20 billion. Patients that are AAV5 positive, the vector using ROCTAVIAN, that's another $9 billion. Treating younger patients. Right now, the product is only approved for age 17 and above. That would create a total market, cumulative market opportunity of about $32 billion. Just wanna highlight also that, you know, one of the strengths of BioMarin is our biologics manufacturing capabilities. We own all our manufacturing facilities. We believe that for biologics, it's fundamental to control your manufacturing because your product is approved with the plant that makes it. The plant is the product in some ways. You know, on the right side of the slide, we've had several biologics facilities that have been ongoing for over 20 years, in Novato and one in Shanbally, Ireland, which is 200,000 square meters. More recently, we have built a state-of-the-art gene therapy manufacturing facility, which is already approved, was inspected twice by the EMA, and it's been approved for usage for selling in Europe. This actually facility has received, you know, several awards, it's the only facility that where for BioMarin products that we start absolutely from ground zero from scratch. At the end of the plant, at the exit, you get the vials packaged, you know, ready to go, ready to be shipped to the hospital. We have a substantial track record of global inspections and cGMP compliance, and we are very proud of our, you know, manufacturing asset here. With this, as I said, you know, accelerating the pipeline is one of our key priorities here. With this, I'm gonna let you know, Hank Fuchs, our President of Research and Development, say a few words about our pipeline. Thank you, JJ. It's nice to see everybody in person. Thanks for your support for BioMarin. Over the weekend, we released the most recent tranche of data from our ongoing follow-up of patients who've been treated with ROCTAVIAN. Just to orient you to the slide, we have a group of patients over 100 of whom were dosed more than three years ago. In addition, we have 17 patients who were dosed more than four years ago. We're accumulating quite a bit of data on durability of ROCTAVIAN gene therapy. Three years after a single dose of ROCTAVIAN, median factor VIII levels, and four years after a single dose of ROCTAVIAN are in the range that we expected them to be based on our prior Phase I/II study and provide substantial hemostatic effectiveness as evidenced by the maintenance of relatively low bleeding episodes while patients are off prophylaxis. To remind you, if you are not on prophylaxis, you'll bleed 20 or 30 times a year, and best standard of care is around 4.8 bleeds per year. This represents best opportunity for patients to have both the benefit of low bleeding and unbuckled from the burden of chronic therapy. In fact, when one looks at annualized bleeding, the annualized utilization of factor VIII at the baseline, this was over 130 infusions per year, and we've knocked that down in the population to around eight or 10 infusions per year. We're very excited about the sustained durability of ROCTAVIAN. As JJ mentioned, we'll be sharing these data with the Food and Drug Administration shortly. One of the concepts that we've been exploring about ROCTAVIAN is how to sustain durability in the event durability continues to decline. We've learned a lot about controller of protein expression from human studies. On that basis, we've been able to identify some mechanisms that enable increased expression using small molecule drugs. Some non-clinical data as well as some human liver biopsy data that we've developed from ROCTAVIAN and actually published has indicated, progressive transcriptional failure of the episome. The DNA is still in the liver, but over time the DNA gets silent, the transcription of the DNA into RNA gets silenced. On the basis of that, we were able to screen several small molecule drugs that modulate this silencing mechanism, and have identified some promising candidates, one of which is shown on the far right. Just to orient you to the slide, we created an experimental system in which we've been able to deliver the transgene and then silence its expression, much like we see in ROCTAVIAN-treated patients, add increasing concentrations of this FDA-approved small molecule drug, that can be taken relatively simply by patients, you know, year, potentially years after they've received their dose of ROCTAVIAN. You can see at a tenth of the concentration of the drug, that's used already therapeutically, we can increase transcription by 13-fold, which is more than enough to restore expression back to original levels. In fact, this phenomena is dose-dependent, and can actually restore protein expression or transcription quite a bit. The next steps here will be to investigate this in humans. This is pretty exciting because, the concept would be that, again, years out after a single dose of ROCTAVIAN, if factor expression is declining, we can reawaken expression and, render the patient in a more stable hemostatic zone. I mean, and it could apply to other AAVs. Conceivably could apply to other AAVs to the extent that they are experiencing those things. This is foundational and fundamental to the whole AAV gene therapy field and really comes from the fact that we have the largest and longest duration of follow-up of patients treated with gene therapy. Several years ago, as it was looking like ROCTAVIAN and VOXZOGO were gonna work in humans, we had to pivot the pipeline to start steering towards larger therapeutic areas. I've talked about in the past the concepts of leverage that we're seeking, which is to create therapeutic areas of foci within a particular indication to have potentially several different molecular approaches to the indication and to leverage the breadth of platforms that we're able to work in, whether those are small molecules or peptides or biologics or larger nucleic acid delivered therapies. That's been pretty robust in terms of the expansion of the pipeline. Also fueled by the fact that as the genetic revolution continues, we're discovering more and more conditions which were in the olden days ran in the family, but now we can understand that they are mediated through a series of genetic disorders, in a lot of cases, haploinsufficiency disorders. In this chart, what you can see is that we're now entering in phase I trials, and I'll show you some emerging data from our phase I programs, as well as we have a bead on IND enabling activities to support the continued growth of the pipeline. In fact, our next two INDs are pretty well-identified. The two INDs after that are pretty well-identified. In the research programs, we've actually in several of the cases identified the specific molecule that's gonna be used as a therapeutic, and we're working with our tech ops teammates to develop manufacturing and formulation to enable clinical trials to ensue. In the amalgam, these represent gigantic opportunities for BioMarin based on patient numbers and medical opportunity to serve. I wanna talk about a couple of these with and provide you some emerging data. The first of these is BMN 255 for progressive renal failure and recurrent kidney stones in hyperoxaluria. This is a well-established therapeutic pathway in the sense that there's already an approved drug. The condition is mediated originally in the genetic form through AGXT deficiency, which results in accumulation of oxalate in the urine, and oxalate crystallizes in the urine and can cause painful kidney stones and progressive renal failure. The molecular pathway for this is shown on the left. The AGT mutation, which is present in an inherited form in terrible renal disease in children, for which there is an approved therapy, already validates the pathway as a pharmacologically tractable target. We developed a small molecule inhibitor of glycolate oxidase, which prevents the conversion of glycolate to glyoxylate, glycolate is then excreted in the urine. On the right is the result of a single ascending dose study that we've concluded. We've actually also concluded the multiple ascending doses studies and demonstrated the safety, but I wanna show you the recently available data. You can see the placebo at the bottom and in the right in the black... I'm sorry, on the right side in the black are, is mean increase in plasma glycolate, an indicator of the effectiveness of the knockdown of the inhibition of the relevant enzyme. The dashed line indicates where that FDA-approved product is. We're about five times more potent with this molecule in knocking down oxalate production, and we hope to be able to translate that into patients with chronic liver disease who now interestingly are found to have epigenetic silencing of the same enzyme. This is the rare to common dream come true in the sense that we can find the genetic disease which occurs rarely, but the more common form of that through epigenetic silencing and a much more common condition in a subset of patients with liver disease. We're very excited about these data. Switching now to our next gene therapy, BMN 331 for hereditary angioedema, which is like hemophilia in the sense that it poses a chronic lifelong burden of therapy. As you can imagine, deficiency of this particular protein genetically results in the reduction of an inhibitory protein. The effect of that is that patients experience these terrible episodes of breakthrough hereditary angioedema, and these can be life-threatening. The available therapies on the market establish the therapeutic pathway, much like in the case of replacement factor VIII therapy in hemophilia. But like in replacement therapy for hemophilia, they cannot provide enduring compensation for the loss of the deficient protein. In fact, troughs of activity can leave patients vulnerable to recurrent episodes of hereditary angioedema. We've shown in three clinical studies with BMN 331 gene therapy that in mutant mice and in non-human primates that a dose that's similar to our ROCTAVIAN dose can provide ample expression of C1-esterase inhibitor within an acceptable range in patients to prevent the HAE attacks. Here are some data from the first study of BMN 331 in humans, two different dose levels, 2E13 and 6E13. In contrast actually to ROCTAVIAN, we're actually already seeing a little bit of activity at the 2E13 dose in one of the two patients, but we chose to dose escalate. The first patient who's treated at 6E13 is almost practically in the normal range to prevent HAE breakthrough attacks. As in the case of Roctavian, this represents a pretty substantially valuable effect in the sense that to achieve this kind of a level would require about $500,000 worth of replacement therapy. If we can document the safety of this in larger number of patients, we'll be looking at a Roctavian-like development program for BMN 331 for hereditary angioedema to provide the normal physiologic protein replacement. We anticipate several other INDs that are on the track actually. For example, BMN 351 for Duchenne muscular dystrophy. It's an exon 51 oligonucleotide skipper. Unlike our prior programs and unlike everything that's on the market, BMN 351 targets a novel splice site enhancer and is in fact more than tenfold more potent in facilitating exon skipping. At concentrations that we already know we can achieve in humans based on our experience with risdiplam, if we achieve those muscle concentrations in humans with BMN 351, our anticipation will be that there will be more than 20% dystrophin produced. This is at least twice as high as the amount of dystrophin produced by a much milder form of Duchenne, called Becker muscular dystrophy. Well on our way to initiating treatment of patients with that. Next IND will be BMN 349 for alpha-1 antitrypsin. This is a small molecule, rapidly acting orally bioavailable medicine that binds to mutant A1AT and solubilizes polymers that increase in the liver. We've shown preclinically that the reduction in polymer burden in the liver of affected animals improves overall liver health. We'll be putting this into the clinic with the intention to explore the therapeutic advantages of a pill for alpha-1 antitrypsin liver deficiency. Next on the list is BMN 293 for myosin-binding protein C3. It's a hereditary cardiomyopathy abbreviated HCM. This is gene therapy. We've created a cardiac-specific C3 gene-containing cassette that's delivered by AAV, very similar to our ROCTAVIAN and BMN 331 programs. We've shown in preclinical models that we can achieve durable rescue of the hypertrophic phenotype in animal models and improvement in cardiac function in a rescue context. We're very excited to bring that forward for patients as well. Each of these new indications are themselves addressing much larger patient populations than historically we've been addressing, as I mentioned on the previous slide. These are much larger patient populations than historically BioMarin has been addressing. These are very, you know, they have the potential to be very high-value mechanisms by virtue of affecting the fundamental genetic defect that's responsible for the condition. With that, I'll turn it over to JJ to wrap it up. Thank you, Hank. Again, we go to, you know, our history is to create, you know, markets that address unmet needs. We have created the MPS disorder market. We have created the PKU market. We have created the achondroplasia market. Now we're about to create the hemophilia gene therapy market. That's the plan on a going-forward basis. I talked about sustainable growth and profitability being one of our key strategic priorities. You know, we really now are planning on accelerating revenues and profitability over the next few years, thanks to the expansion of VOXZOGO and the launch of ROCTAVIAN. We anticipate double-digit revenue growth in 2023 from the base of $2.09 billion in 2022. We anticipate being between $4 billion and $5 billion in revenues by the middle of the decade and continue to grow to the end of the decade, continue to fuel the growth thanks to all the exciting products that Hank just talked about. With this maybe I'm gonna have, you know, Brian Mueller, who's our Chief Financial Officer, say a few words about this slide. Brian? Yeah. We'll be happy to talk about this over the coming weeks, but when we report our fourth quarter 2022 and full year, we're gonna announce some planned new financial metrics for 2023 and beyond. Just to keep it simple for the sake of time here, we're evolving our non-GAAP income methodology, which we consistently reported for many years. Given the profitability, given the maturity of the business, we feel that we should evolve that metric, and we're also evolving how we give financial guidance going forward to be more meaningful to investors in the Wall Street community. All right. Thank you, Brian. I think we've talked about all this, since we went over time a little bit, I wanna leave a little time for questions. Thank you for your attention. Jess, the floor is yours. Great. Again, if you have a question, wanna raise your hand and ask it, feel free. Otherwise I will start. Maybe starting with ROCTAVIAN, I think you had your facility inspected recently. Any last deliverables on the manufacturing side as part of that FDA review? Greg, do you wanna say a few things about this? Mm-hmm. We have our chief tech- Have a seat. Our Head of Technical Operations here, Greg Guyer. Actually there's a seat left for you, Greg. Thanks, Jessica Fye. Very rarely get manufacturing questions, so this is awesome. I think the reason is because it's so important in the space of gene therapy because it really is as a differentiator. We're ready to go. We've responded, as Jean-Jacques Bienaimé said, to the comments that FDA left us. It was intense, inspection for a week by five investigators, but it all went well, and we're ready to go, preparing for launch. We've responded to all the questions, and we've heard nothing back from them. Actually won't hear anything back with them until we hear on the PDUFA date. So far so good. We're ready to go. Again, this facility has been inspected twice and approved twice by the EMA. Mm-hmm. Just wanna remind this. Okay. Another question clarifying one of the comments you made during the presentation, JJ, about I think you said you were comfortable with ROCTAVIAN consensus for 2023. Was that the worldwide consensus number or the US consensus figure? Cause I know- World-worldwide you sort of qualified it. We'll provide detailed guidance, you know, when we report Q4. Okay. I did say it assumes, however, that we get approval in late March. You know, so it could be a little different if it's delayed three months because of the phase III data submission. I mean, the year three data submission. Have you gotten any indication from the FDA either way about whether they might extend the PDUFA? Until we file, Hank, you wanna go? We've been in some discussion with them about what they'd like to see, but they haven't tipped as to whether this will result in a PDUFA delay. I think that, I mean, on the one side, the data look fairly simple and pretty easy to understand, and they've already been in review for a while. With the application, on the other hand, there are a lot of things that go on at the FDA that are sort of behind the curtains that make it a little hard for us to speculate as to what their action is gonna be. I would say, you know, we're pleased with the year three data. Could have been going a different way. I would say for sure, I don't think it reduces the probability of approval here, kind of probably increased it. Okay. I know investors were pretty pleased to hear that the FDA's not planning on a advisory committee at this time, or I guess at that time. Is there any chance an advisory committee comes back on the table for this application? There's always that chance. You know, I think that the fact that they pulled back from it, I think augers well as to I don't think they'd have pulled... Having told us that they want one to then do it a third time would be, you know, to change their mind again would be a bit unusual, not completely, you know, without imagination. You know, I think the dialogue has been great. We had a pre-BLA meeting with them last year. They asked for a lot of additional information, which was we were originally planning on filing in June of 2022, and that caused us to push back our filing date to September of 2022. They, they've already had a lot of time to go back and forth with us. In the three months since we've conducted the app... since we submitted the application, we've already been back and forth with them a lot. I think the fact that they announced that they don't need an advisory committee says that the issues that whatever they were thinking about in the first instance have now been addressed through that back-and-forth dialogue. The fact that they approved Hemgenix for, you know, gene therapy for Factor IX, you know, clearly shows that they are more and more comfortable with AAV gene therapy for non-lethal indications that have already available treatments. I also think the data are pretty self-explanatory in terms of therapeutic benefits. I think that helps us quite a bit as well. I know you're pursuing these OBAs or outcomes-based agreements in Europe, and you've got at least one signed in Germany right now, with a couple more to come. How should we think about the U.S.? Is there gonna be anything similar in your-? Yes. kind of US reimbursement piece that look like? Yeah, there will be. We're already in talks with payers. I mean, you wanna go over that, Jeff? Yes. Jeff Ajer is our Chief Commercial Officer. Hi. The U.S. situation could have been very complicated, but in fact, we've boiled that down. As J.J.'s slide showed, our intention is to offer a warranty that essentially becomes the outcomes-based agreement and covers risk of non-performance for US payers. A warranty structure, you know, think about the warranty you get with your car. Comes with the product. You don't negotiate the terms, it's just there. It's been very well-received by the payers that we've pre-run that with. Importantly, we think that the warranty structure avoids some of the worst complications that could have arisen with, you know, some kind of outcomes-based agreement structure that isn't a warranty in the United States with respect to government pricing. You wanna explain very briefly with an example what we mean by this, the four year example? Yeah. Payers don't like risk. They don't like uncertainty, particularly with high-value therapeutics. What we know is payers have been concerned about risk of product non-performance and over time, so essentially durability. At a very low cost, we can take that risk off the table for payers. Allows us to capture maximum value. As you saw from the Hank slides, 92% of patients remained off of prophylaxis therapy at the end of year three. To use a very simple example, if we warrantied the performance of ROCTAVIAN for four years, means that we would provide a linearly pre-prorated reimbursement of the cost of ROCTAVIAN for the portion of time during that four year window of non-performance. To use a simple example, patient that started bleeding and went back to prophylaxis on, at the end of year three, would have consumed 75% of the value of the purchase of ROCTAVIAN, means we would re-refund that payer back 25%. Other questions? Maybe switching to VOXZOGO, the uptake has looked really good. Can you talk about some of the real-world feedback you've been getting on, like, how the product profile is holding up, say, relative to the clinical trial data? I'd be happy to do that, Jess. Voxzogo, I think, is a perfect example of when you have a powerful unmet medical need, no good standard of care treatment, and you come along with a new and innovative drug that provides very relevant outcomes. In the case of VOXZOGO, that's linear growth. The uptake has been really rapid so far. JJ reports that we've got over 1,000 commercial patients treated as of the end of 2022. The uptake quarter by quarter has been going really rapidly. We're anticipating that that will continue going forward. There's a lot of interest in treating young patients in particular. One of our most recent launches was in Japan at the end of August. We have an age agnostic label in Japan. There's been a lot of interest in treating very young patients in particular, and I think that makes JJ's comments about the age expansion into younger ages in Europe and the United States very poignant. That'll be a high-value market expansion segment to get into. Yeah, our youngest patient in Japan was treated when he was three weeks old. Or she, I don't know if it's a girl or boy. Maybe we can stick with VOXZOGO a little bit. Are there any different regional dynamics you're seeing, i.e. are there some regions where uptake is even swifter? The uptake really is guided in a lot of markets by getting price and reimbursement settled and gaining market access. Early access or early uptake was driven by Germany. We've still got a lot of room left to grow in Germany, we recently finished price and reimbursement negotiations in France and Italy. Those are big strategic markets and are gonna contribute a lot of growth in 2023. As I said, the launch in Japan, which came with full market access, age agnostic, started in August. That was kind of a driver of uptake late in 2022 and will be throughout 2023. The launch in the United States, where we capture the most value per patient, in ages five and older, has been going really well and will continue to do so during the course of this year. We've got other markets that require a registration approval beyond the US and the EMA and Japan. Places like Brazil and Australia, where we have relatively recent approvals will continue to contribute uptake. We've got more registrations in process. Expect to see more registration and approval activity, which opens up new markets for us over time. Yeah. Again, we see the addressable markets in achondroplasia alone is around 18,000 patients. With 1,000 patients, we still have a long way to go before fully penetrating this market. Maybe one on the financial outlook. You talked about kind of sustained profitability and margin expansion. Is it possible to quantify the kind of magnitude or degree of margin expansion we can be looking for over the next several years? Yeah, thanks, Jess, great question. You know, just to start, you know, the basis for this journey into margin expansion for the company starts with this profitable base business that we've built. We recognize the company's been around a little more than a couple of decades and has operated at, you know, GAAP net losses during most of that time. It was by design within the strategy to build this world-class infrastructure that started with these ultra-rare disorders, but can now be the basis to launch these much larger market opportunities. With that as the backbone, we expect margin improvement across the board, all the line items. VOXZOGO and ROCTAVIAN are expected to have a lower natural cost of goods sold, therefore higher growth margins at the growth margin level. SG&A is a leverage story. We've built this infrastructure. We sell in 78 markets today. That's part of the story behind this rapid uptake for VOXZOGO, is it's leveraging the same, sales and marketing infrastructure that we built for the base business. R&D expense, interestingly, decreasing as a percentage of revenue over time, so margin expansion, but increasing on an absolute dollar basis. Increasing the investment in that early-stage pipeline. You know, you could do math different ways, and there's different spots on the journey, right? There's that middle of the decade that JJ referred to at that $4 billion-$5 billion. We don't expect to stop growing there either. That's why we're investing in these early-stage products. We finished JJ's presentation by saying, you know, we're committed to large biopharma profit margins. That's in the 30% ± range. Okay, great. We'll leave it there. Thank you. Thank you.