Great. Good afternoon, and welcome back to the 40th annual J.P. Morgan Healthcare Conference. My name is Cory Kasimov. I'm the senior large-cap biotech analyst, and it's my pleasure to introduce BioMarin and Chairman and CEO, Jean-Jacques Bienaimé. Please note that following this presentation, we'll move right into the Q&A session where you can send in questions via the conference portal, and I'll do my best to work those into our conversation. With that, JJ, thanks as always for being here. Thanks as well for putting out some good data ahead of the conference. Let me turn things over to you for an update. Okay. Thank you, Cory. I'm on slide one here because I cannot actually see the slides that are on the screen for you, so thank you for listening today. I'm moving to slide two of the presentation that has the safe harbor statements. I just wish to highlight that I and some of our other BioMarin executives might be making some forward-looking statements during this Zoom call. Please refer to our filings with the SEC for more information. Next slide, please. Slide three. As you can see on this slide, over the last few years, we have successfully pivoted our pipeline, which has touched each core capability that defines BioMarin. We are leveraging the underlying expertise that we have in genetics that has enabled the therapeutic and commercial success that built the foundation of the company. In starting with discovery on the top left, we can apply our scientific principles now to larger indications, larger genetic indications, larger orphans and potentially beyond orphans, but staying within genetics. In development, we have honed our clinical development expertise and regulatory experience to drive greater efficiencies from discovery to approval, and we have now seven product approvals, waiting for eighth one with Roctavian, hopefully this year. On the commercial fronts, we have built a global infrastructure that is unmatched in the industry for a company our size, especially in the genetic disease space, with a direct presence in over 75 countries now. Finally, key to all these developments, working effectively together, we believe we have built the best-in-class, fully owned manufacturing capabilities, and a set that has served well throughout the development process with Roctavian, and our other gene therapy products. We have unparalleled capabilities in complex biologics manufacturing and gene therapy manufacturing. Next slide four. See here on this slide is a framework for the pipeline pivot it enabled our durable foundational business, which is in the first left circle here. This has been a foundation upon which we have built our expertise as a fully integrated global organization. In the middle circle, the circle two, we have our two blockbuster products, VOXZOGO for achondroplasia, which was approved globally last year, and Roctavian, potentially the first gene therapy treatment for severe hemophilia. We expect VOXZOGO alone to drive us to sustainable profitability this year. With Roctavian potentially layered on it, we would expect a significant top and bottom-line improvement and trajectories in the coming years here. Another key component of our horizon value is the earlier stage pipeline of next generation therapies, many of which we highlighted recently at our R&D day call. With these components, we believe that we have created the virtuous circle of invention at BioMarin that is creating value for patients. We create very significant shareholder value and employee fulfillment. This delivers more value for more patients, and so on, as we use the financial resources created by our now, you know, seven products in the market, to fund new discoveries and new product developments. Next slide five. Also I just wanna highlight again, this is a brief history of our revenues here. Obviously this year, the 2021 was challenging not only because of the pandemic, but also because this was the first full year that we were facing generic competition in the U.S. for Kuvan, which used to be our largest product. But despite that, we're gonna have revenues in 2021 are gonna be pretty similar to what we had in 2020. We anticipate now pretty significant growth in the coming years. Also, I just wanna highlight on the right part of the slide that the U.S. is quote-unquote, "only 45% of our revenues." It's obviously pretty important, but at the same time, it is somewhat different from other larger biotech biopharma companies where the U.S. is more than 50% of the revenues of the companies. For us, we are a true global company, and as you see on the green side of the slide, Europe, Middle East and Africa is actually a very important component of our business. So is Latin America, and then the rest of the world. The rest of the world is growing with the launch of VOXZOGO, which I think will have a significant presence in Asia-Pacific. Next slide, please. Slide six. Here also, you know, our U.S. opportunities are addressing, you know, larger patient populations, as you can see on this slide. In purple are the number of patients for achondroplasia. In red boxes, in the different regions of the world, the hemophilia A, severe hemophilia A patients, because these are much larger patient populations than what we have addressed in the past. I also wanna highlight that, this is just a severe hemophilia, which is 60% of hemophilia patients. If you look at it, the entire hemophilia market is north of 100,000 patients in the world, excluding Asia, you know, China, India and Africa. The severe hemophilia A market will be our initial target with Roctavian. Next slide seven. Again, I want to, as you probably know, we got approval last year in 2021 in the U.S., Europe and Brazil for VOXZOGO already. The global launch is on its way. It's cascading across multiple regions, and it's so far a pretty successful launch. Next slide eight. Again, we got approval first in Europe in late August, then the FDA approved the product in late November, Brazil also in November. The significant launches this year are gonna be among many other ones, but Japan is gonna be a very significant approval here, hopefully in the middle of this year. This is the second-largest country in terms of market size potential for VOXZOGO after the U.S. So far Japan has not been a very large country for us, despite being the second-largest pharmaceutical market in the world, but I think that's gonna change with VOXZOGO. For the first time, we have a product that has a substantial market in Japan, is gonna propel the Asia-Pacific regions as a share of our overall business. Next slide nine. VOXZOGO is our largest pediatric opportunity to date, as you can see on this slide. If you look at the patients, achondroplastic patient population around the world, between the age of you know birth and 18 years of age, we're talking about 21,000 patients that will be eligible for therapy for VOXZOGO. Again, there is no approved product besides VOXZOGO on the market. There's 21,000 patients at, you know, $150,000 a year, which equates to a $3 billion market. Obviously, our largest opportunity to date. That excludes, again, India, China and most of Africa, which would more than double the number of patients here. Very exciting launch and opportunity for us. Next slide 10, please. As you can see on this slide, again, VOXZOGO is our seventh product launch, and it's so far the strongest launch in the history of BioMarin, right? We have already many prescriptions that have been written for VOXZOGO. The demand is very strong. We now have, at the end of December, we had seven active markets in the world with revenues. Total number of commercial patients at the end of This was our first quarter on the market in Europe, was about at least slightly over 100. You know, we started shipping the product in the U.S. around Christmas. I will provide 2022 VOXZOGO guidance in a few minutes. Next slide 11, please. Just wanna highlight that, you know, this is just the beginning of a great adventure here with this product. Now we're approved for achondroplasia for patients over two years of age in Europe, over five years of age in the U.S. We have an ongoing study in patients from the randomized placebo-controlled trial that is almost finished. We'll have the top-line data by the end of this quarter. We're gonna have some data for achondroplasia patients from birth to five years of age, which will allow us to expand the indication in the future. We'll be filing in the second half of this year to expand the indications for above five years of age in the U.S. and two years of age in Europe to like basically being indicated from birth. That's very important because the clinical benefit is gonna be more important if you treat the patients early. Achondroplastic patients lose growth opportunity every month, basically every year. They will never get it back. The younger you treat them, the better. That's even more important, considering that the patient's growth velocity is the highest at birth, then it goes down every year pretty quickly in the first five years of life, and then it goes back up right before puberty. There's a lot of loss of growth in the first five years of the patients. Also, I wanna highlight that achondroplasia is just the beginning and the first indication for VOXZOGO. We have some studies going on exploring the use of Voxzogo in other genetic short stature indications, and this could dramatically expand the revenue opportunity for VOXZOGO beyond what I demonstrated, I mean, discussed with you earlier. Early clinical data is going to be presented on some of those indications at a scientific meeting led by Dr. Dauber, who is doing the trial in early next quarter. Next slide 12. So as you know, we announced yesterday, we shared with you the two-year data from the largest phase III gene therapy study in people with severe hemophilia A, with a total of 134 patients, as well as data from a subset that goes beyond three years. We're very excited about the results. The study met all primary and secondary efficacy endpoints and demonstrated superiority over standard care, which is still treatment with recombinant factor VIII injections, you know, two to three times a week. We've shown a durable, consistent bleeding control in both our phase III and our phase II programs. This confirms our long-term, you know, long-held belief that Roctavian gene therapy is a transformational treatment option for patients with hemophilia A. We are delighted that our perseverance and focus on bringing this innovative treatment to patients has resulted in the update that we shared with you yesterday. Next slide please, slide thirteen. You know, these are again some of the key highlights from, excuse me, the phase III two-year updates. Roctavian demonstrated superiority to factor VIII prophylaxis, again, which is the current standard of care in the primary analysis of the primary endpoints, with a mean adjusted ABR of 0.8 from a baseline of 4.5. 0.8 treated bleeding episodes per year, so dramatic reductions. Again, not as compared to placebo, as compared to the standard of care. The time frame for this result is the mean AVR through the entire two-year evaluation period. It is a very durable and highly statistically significant. We have 10 zeros after the decimal, and one that is consistent with our phase II results. The mean factor activity levels at year two were 23 international units per deciliter using the chromogenic assay, 36 IU per deciliter using the one-stage assay for the 132 patients in our study. I would say we couldn't ask for a better result on the factor VIII activity levels, especially given the consistent results and the alignment with factor activity observed in our phase II program with both the low 40 dose and the high 60 dose. The ABR for the 17 subjects observed for three years, we have now data for 17 subjects that were treated over three years ago. At that time point was 0.61, again, from a baseline of 4.6. A dramatic improvement and also an improvement over the two-year results. I would say given the unprecedented nature of these results, we have held a lot of details for disclosure at upcoming medical meetings. The contributions from the hemophilia community has been key to the development of Roctavian, and we want to allow them to share in this groundbreaking and truly transformational scientific discovery in the appropriate forum. Next slide 14. Again, this is a summary of some of the key finding. Roctavian significantly reduced the mean annualized factor VIII infusion rates in the rollover populations, going from 130 infusions per year at baseline, when they were on prophylactic factor VIII infusions, down to, you know, 3.4. I would say 98% reduction in factor VIII infusion with a P value of 0.0001. I can tell you that health insurers, the so-called payers, are gonna like this data, because factor VIII infusion is what costs them a lot of money. Also, you know, if you look at, you know, Hemlibra or Hemlibra, which by the way, at one or two years didn't have any AVR. Their baseline was the same as us, but it was a different study, but the AVR was not lower than ours, which is also lower here. Hemlibra cost is around $750,000 per year for non-infant adults, non-inhibitor patients. You can see the pharmacoeconomic value that Roctavian can provide here. We're looking forward to discussing in detail these results with payers in the coming months. Next slide, please. Nice. Slide 15. This one is a summary in one table of all the data that we've been providing over the past five years, during the development of this program, that shows, you know, all the data at different time points in the phase III trial, the phase II trial at high, at low dose, the phase II trial at high dose. You can see consistent over the years, bleeding control and also consistent between the phase II study and the phase III study, the bleeding control, the factor VIII utilization, and actually the factor VIII level. We are very excited about these results. We believe that these results, you know, answer the questions, the key questions that were raised by the regulators, especially the FDA, in terms of the durability of Roctavian once steroids have been removed from the patient therapy after one year of treatment. In terms of safety, the results are consistent with what we observed with Roctavian in the previous analysis, in the previous studies. The drug continues to be well tolerated. Most patients had discontinued any corticosteroids by year one, and there was no corticosteroid-related SAE, severe adverse events, in the remaining patients between being tapered off steroids and year two. Overall, the most common adverse events were associated with therapy with Roctavian, transient infusion reactions and mild to moderate rise in liver enzyme, with no long-lasting clinical sequelae. No participants developed anti-factor VIII inhibitors to factor VIII. There was no malignancy highlighted or uncovered in the phase III trial, and no thromboembolic event. The fact that patients don't develop inhibitors to factor VIII is very important because in case in a few years if we need to go back to factor VIII, if the efficacy wanes, they can go back to what they're doing today, and the efficacy of the factor VIII injection will be the same as today. During year two, no new safety signals emerged. No treatment-related SAEs were reported. Next slide 18. Fast-forward, as you know, we had refiled in Europe in December of last year. When we refiled, it was clear and discussed with the EMA that we will be submitted this two-year data before they make a decision. This was planned, and there's no surprise here. We still anticipate we're gonna submit this information to the EMA in the coming weeks, and we anticipate receiving a potential CHMP opinion in the first half of this year, and a potential approval and launch in Q3 of this year. Regarding the FDA, we are planning a pre-submission meeting with the FDA in this quarter. We just got the data this weekend, so we haven't been able to talk to them much yet. We're planning on meeting with them for a pre-resubmission meeting. We're targeting the submission in the second half of the second quarter of this year. Since this is a response to the CRL, the review time in that space is six months. Assuming we refile by the end of June, we should be able to get an FDA decision and hopefully approval by the very end of this year. Next slide 18. I just wanna say a few more words about our pipeline, which we highlighted, you know, last November during R&D Day. We believe that the pipeline, our pipeline of innovative product candidates, will drive many meaningful profitability over the next few years. Next slide, 19. This is a measure, I mean, a snapshot of our pipeline again from R&D Day, that's illustrating the progress we've made over the past years in different potential indications in hemophilia and metabolic disorders, cardiovascular. We're moving into cardiovascular disorders now, so with gene therapy, CNS and musculoskeletal. The pipeline does demonstrate a rich abundance of candidates, many of which remain unnamed, but they are real programs and projects. In other words, in addition to our disclosed programs that we have talked about many times, we have six undisclosed cardiovascular programs, 10 undisclosed CNS programs, three undisclosed hematology and metabolic disorders pipeline program, and five musculoskeletal programs. Next slide 20, please. Here, this is the most advanced clinical and pre-clinical portfolio. I just wanna highlight here that we have submitted a file to the FDA on BMN 307 for PKU gene therapy for them to remove the clinical hold. We hope to have them remove the clinical hold sometime this quarter and to go back enrolling patients with our PKU gene therapy product because we are starting to see some pretty exciting efficacy signal. I wanna highlight that BMN 351 we anticipate being back in the clinic, back in Duchenne muscular dystrophy with a very effective, potentially very effective product based on animal studies before the end of this year. Next slide 21. Overall, we anticipate substantial revenue growth this year compared to 2021. This is where I'm providing our preliminary guidance for 2024 VOXZOGO. We anticipate the state of launch is going better than we anticipated. Our guidance at this time, and we will provide final guidance when we report our fourth quarter in next month. Our current guidance is $80 million-$110 million for VOXZOGO global net revenues this year. Thanks to VOXZOGO and panels to the growth of our other products, we anticipate now to be GAAP profitable for the full 2022 year, and to be GAAP profitable in a sustainable way over the next few years. That's irrespective of the dates of the Roctavian approval, we will be GAAP profitable. Next slide 22, please. All these, you know, the current products on the market, VOXZOGO will launch and hopefully the Roctavian launch will provide the financial foundation to accelerate our growth. Again, substantial top line growth anticipated in 2022. We will give you full guidance next month. Anticipate sustainable GAAP profitability in 2022. Margin improvements over the next two years. Sustainable positive operating cash flow. We already had positive operating cash flow last year, but now we're gonna keep growing. R&D and SG&A expenses as a percent of revenues are coming down, and will continue to come down. The revenue and the margins will be improving continuously over the next five years to bring BioMarin's financials to a level similar to big biopharma companies. Last slide, it's slide 23. I wanna thank you for your attention, and I wanna return the call back to you, Cory, for questions. Great. Thank you, JJ. I think, if- Other BioMarin executive is supposed to join the call. I think we're in touch with Tracy. I think it might just be you and me for Q&A. Is that so? Is that so? I have to ask you all the tough questions. Oh, okay. You put on somebody else. I think this will be pretty easy. I mean, I guess let's start talking about Roctavian. Can you just kinda speak to what you think were the key takeaways from the two-year update that you provided yesterday and what this means in your estimation for the approvability of the product? I mean, I think based on this data, again, we have, you know, clear evidence of efficacy in terms of bleeding control here. The data is at least as good as the low dose phase II data which showed significant bleeding control for four years and above. The evidence of efficacy of the drug in terms of bleeding control, which is the clinical endpoint, is incontrovertible here. I think even if you do all sorts of sub-analysis, subgroup analysis to try to figure out if there's something wrong with the data, that's gonna be very difficult when your p-value is 10 zeros after the decimal. We believe that we have shown clear evidence not only of efficacy but superiority or standard of care. We believe that this data is very likely to answer the questions that were remaining for regulators in order to approve the product. We're gonna be actively discussing this with them. We see the probability of approval of Roctavian has been going up dramatically with this data at the end of the day. Okay. If I may, I'd like to highlight the data provides substantial evidence of cost-effectiveness of Roctavian, even beyond what was established before. You might remember that ICER had done an analysis back in 2020, you know, right before we got a CRL. At that time we got even the full one-year phase III data, now we have a two-year. With less historical data on the phase II, they had determined that in the U.S. Roctavian would be cost-effective at $2.5 million a patient. Essentially this data reinforces this analysis and, you know, significantly improve the commercial potential commercial value of the asset. Okay. You know, feedback I got on the data overall has been promising. The only areas of pushback, not surprisingly, have been around factor eight levels. You know, how comfortable are you with that segment of the results, and what do they suggest to you about the ultimate durability of the product? I mean, you see the factor VIII levels again at year two and actually for the 17 patients at year three, I mean at year two for the full patients they were actually a little bit better than the factor VIII levels in the first 17 patients at phase II. Now we show that there is maintenance of factor VIII level at year three, that we show now that at year two the factor VIII levels are between the high dose and the low dose of the phase II trial, which has shown durability for five years and above, and we're gonna have six years in the summer actually. By the time we launch Roctavian even in Europe to get approval in Q2, we will have six years of demonstrated, you know, bleeding control. Actually there are some models that exist to project, you know, durability or efficacy based on the existing data, and I've seen a model that projects at least seven, eight years of durability here. It could be even more. I think we're learning as we go here. We're the first, you know, the first company in history to establish the relationship between continuous transgenic factor VIII expression and bleeding control. I would say that the data is pretty clear that the bleeding control is pretty substantial. Even the bleeding control at four years in the low-dose phase II trial was pretty good. It was around one point one bleed per year, if I remember. I think it's unlikely that Roctavian is gonna be a lifetime cure, we're not making that claim. I would say it's very likely it's gonna be effective for at least six or seven years or maybe more, which is substantial value for the patients. Especially considering that they can still go back to what you're doing today, whether they are on recombinant factor injections, prophylactic therapy or Hemlibra. They can go back to what they are doing today after seven, eight, nine years, whatever it happens for them, if it doesn't work. Okay. On the regulatory front, I know we're expecting a CHMP opinion in the first half of this year. When you think about the U.S. dynamics, recognizing you have to meet with the FDA this quarter, what are the key gating items to resubmit the BLA, especially considering you've already filed it once? It's basically a refiling answer to their complete response letter, so it's a somewhat more focused filing. We do need to put the data together. Obviously, we got the data this weekend, so we haven't had time to communicate with them much to determine what are the next steps. We're planning on meeting with them this quarter to have, like, a pre-resubmission meeting which will determine what they need to see. We believe that this data answers most if not all of the questions that I've been raising so far. Remains to be determined what else they're gonna have. I think one of their reviewer's key concern was the. What she was concerned about the fact that maybe factor levels will collapse after one year once the patient's steroids were withdrawn and the data we have, and we're not disclosing everything today, clearly demonstrate that is not the case. I think that was one of the key issues. The factor levels, yes, they do decline, but they don't collapse, you know, between year one and year two. They are pretty similar to what we saw in phase II again, and I think that's gonna go a long way to answer some of their questions. Okay. What does your market research suggest about the percentage of severe hemophilia patients that are potentially interested in a treatment like this, a gene therapy treatment? You know, the market research, we're doing market research regularly. We did it before, you know, the CRL, and we're doing it, we've been doing some in the fall. Interest in the drug is still very high. What's interesting is that even patients that are currently using Hemlibra, our market research last fall in U.S., Germany and France found that a third of eligible patients currently taking Hemlibra were considering switching to Roctavian in the first year of availability. I mean, that's a large number of patients. Also we found out something that was surprising is that the patients who are still on recombinant factor VIII injections, which is the majority of them in U.S. and Europe today, the ones that have not tried Hemlibra yet, they're interested to go straight to Roctavian without stepping through a switch to Hemlibra. That was a surprising finding, positive finding for us. We believe that the demand for Roctavian is gonna be pretty high in the first few years of launch. Okay. I wanna move over to VOXZOGO and first ask about the launch and specifically the guidance that you're providing for 2022. You know, numbers are kind of all over the place out there in the street. The consensus is, like, $120 million. Our estimate is way below that at $69 million. Your sort of your guidance is right in between it. How much confidence do you have in providing guidance for a product like this this early in the launch? I would say this is based on, you know, what we're observing right now. I mean, we're gonna be reporting our 2021 sales, which we're gonna be, like, a not even a whole quarter, first quarter, basically only U.S., European sales. You will see that they are indicative of the interest in the product. The fact that we have a lot of analytical evidence that, you know, even U.S. kind of pediatricians and patients' families, they are reaching out to us to get their patients started on therapy. I would say all this points towards, you know, pretty strong launch. I think that we are pretty confident in the guidance that I've just given, although we might change a little bit in, you know, next month when we have more information on the U.S. launch than we see at this time. Based on everything we know, we've been, you know, working on this launch for several years, and we're pretty confident in this guidance. Okay. Do you think there's anything that You have to raise your numbers. Sorry. Yeah, I'm more worried about consensus numbers than I am my own. Do you think that there's anything that others could be missing in terms of whether it's a payer dynamic or some nuances in the market that would get people to go? I mean, no, this is, you know, a brand new launch in a brand new market. Again, we are creating the achondroplasia market like we created the PKU market. We created the MPS I, MPS VI market, MPS IVA, and the CLN2 disease market. That's why it's always a little difficult to figure out what's going on. We are pretty close in this market. We have great relationships with a lot of pediatricians that you know developing relationship with pediatric endocrinologists, relationship with the pediatric orthopedic surgeons. We believe we understand this market very well. I mean, there's gonna be the usual dynamics of reimbursement in the U.S., which we're very, very familiar to because we... This is again our seventh product launch, sixth one in the U.S. We know the drill here. Based on you know early discussions with payers and feedback from payers, we don't anticipate any major issue here. We're gonna have to go through the usual paperwork for initial reimbursement, but we don't believe there's gonna be any significant barrier to this or payer or weekly. Okay, another question from the portal is what's the plan for vosoritide expansion beyond achondroplasia and next generation products for CNP? Yeah. In terms of expansion, as I told you, we have some emerging data from a study by Dr. Balber, which I think he will present at a scientific meeting sometime in Q2, early Q2. This is going to highlight quantitatively for the first time in patients the impact of VOXZOGO on these patients that are not achondroplastic patients, but have a genetically defined and derived growth disorder and short stature. Based on the quantitative statements I think he made at R&D Day, he said the results were very exciting. I actually have seen some of the results, but I cannot communicate them to you, but we are pretty enthusiastic here. Let's talk about this one after he reports his results, and then we'll have to determine which specific indication we go after. We're already working on that plan, but I would say this could dramatically expand the patient population that VOXZOGO would be serving here. That's for the indication expansion. Regarding second generation long-acting CNP, you know, we have some early work. We don't believe there is any urgency, by the way, I'm gonna tell you, because so far the data is very good here with our product. I think it would be hard to beat. And two, the compliance and persistence of our patients. Now we have patients that have been on the drug for, you know, almost six years and has been very high. However, yes, we have a long-acting CNP product that could be potentially given every other week. We are early in development for this. We'll keep you apprised of it. We believe we could have it on the market at about the same time or quickly after some of our competitors if they're approved. We believe we have at least five years of market exclusivity here with no other competitors. Okay. Well, listen, JJ, we are out of time, but thanks as always for joining us today, and I really appreciate it. You're welcome. Thank you, sir.