BioMarin Pharmaceutical Inc. (BMRN) Earnings Call Transcript & Summary

Great. Thank you, everyone, for joining us this afternoon or this morning, depending on where you are. Really excited to have with us for our next fireside chats, BioMarin. From BioMarin, we have J.J. Bienaime, the Chairman and CEO; Brian Mueller, Executive Vice President and CFO. I have a couple of backup people in case -- online. Kripa Devarakonda, one person on my team in case I should disappear, don't worry, the call will go on as planned. So first, I have to read a disclaimer. Before we begin, I have to read the following. This call is arranged by Truist Securities Research for institutional investors and issuer clients as defined by FINRA. If you're not an institutional investor or issuer, please disconnect at this time. For required disclosures, please see our website at truistsecurities.com or our equity research library. And with that, I think I'll turn it over to J.J. Thank you both for joining us today. I'll turn it over to you for maybe some opening remarks.

Thank you, Robyn. We appreciate the opportunity to speak with you today. We recently announced a very strong start to our 2021 calendar year on our Q1 call. We reported $486 million in total revenues for the first quarter. We are also pleased to have reaffirmed our full year 2021 guidance, which is between $1.75 billion and $1.85 billion for this year. And this, despite some headwinds from ongoing COVID impact mainly outside of the U.S. and anticipated uneven ordering patterns in certain ex U.S. regions where we do business. So with the commercial business tracking to plan, we are turning our sights towards our next potential commercial product, which is VOXZOGO for the treatment of children with achondroplasia, which is the #1 form of human dwarfism, which has no approved therapy today. So this is our biggest opportunity to date, and it includes approximately 11,000 eligible children in European, Middle East and Africa, and roughly 3,100 children in the U.S. that will be eligible for treatment. Our commercial team is advancing launch readiness in key EU markets and the U.S. Sales, brands and market access teams are in place, and they are working on finalizing the details of the launch. Just want to emphasize again, there is no approved therapy today for achondroplasia. There is no competition, and it's a very large unmet need for these patients. Released label finished goods are expected to be available in key markets, including Germany, France, Italy and the U.S. and ready to ship to customers within 4 to 8 weeks after the approval. So not only can we leverage our experience successfully launching Vimizim, Palynziq and Brineura, but we benefit from some overlap on medical call points given some of the characteristics of achondroplasia, and I'm talking about pediatric orthopedic surgeons in this respect. Catalyst with VOXZOGO overlap -- I mean, lineup nicely beginning with potential European approval in the summer, assuming a positive CHMP decision in June, followed by the November 20 PDUFA action date in the U.S. The combined market potential in these 2 regions alone represents over $2 billion opportunity. So we are looking forward to these upcoming milestones with great anticipation. In addition with an EMA approval, we can file anywhere in the world, excluding China and Japan, of course, the U.S. Briefly on ROCTAVIAN. Last week, we confirmed our alignments on the FDA on providing complete 2-year data from our ongoing large Phase III trial with ROCTAVIAN and the BLA submission in the second quarter of next year. In Europe, based on very successful presubmission meetings, the EMA is open to our filing the 1-year data to form the basis of our approval. And we look forward to the submission of the EMA -- sorry, the MAA in the Europe next month in June. So we have a lot more to talk about with the earlier stage pipeline which we'll get to in the Q&A. So I will turn it back to you, Robyn, for questions.

Great. So I just thought we'd start off with a couple big picture questions for you. So on the first quarter call, you had mentioned that your 5-year non-GAAP income CAGR of about 62% exceeds the 12% average of biotech companies with at least $1 billion of revenue over the last 5 years and that your 5-year CAGR figure of 16% is better than 10 of the 15 biotech companies that are bigger in revenue and bigger in cap. So how should investors think about the role BioMarin's base business plays contributing to that growth versus like from the new products into larger indications? I think people need to understand the value of your base business basically and how much that's growing.

Yes. So the growth we have experienced in these last 5 years are a good indicator of the strength of our core business and again despite the COVID-19 headwinds. So hopefully, investors recognize that the stable base of revenue is expected to grow steadily over the foreseeable future. Very big investment in larger transformational therapies, including VOXZOGO and ROCTAVIAN. And maybe Brian can give you a perspective as to what to expect in the next 5 years in terms of revenue growth ballpark and profitability. Brian?

Yes. Thanks. Thanks, J.J. Thanks, Robyn. It's a great question. So the -- one important aspect of the growth and the health of the base business is first of all, it's still growing. So we've got some of the revenue headwinds, such as the COVID impact on the business, which -- sidenote there, if you look to last year, while we did adjust our guidance over the course of the year due to COVID, it was just about 5%. So even -- that base business, even in a COVID world was very resilient through the pandemic. And also looking past the Kuvan loss of market exclusivity in the U.S., which started in October, without Kuvan, that base business is still growing at 9% this year if you look at the midpoint of our guidance. And in there is Palynziq, which is still growing over last year at 35%. Brineura, likewise, growing significantly. So the base business is still growing. And importantly, it is expected to be cash flow positive this year. And especially during the year, we -- I refer to it as sort of a hold-the-line year because of some of those revenue headwinds because of our waiting for VOXZOGO and ROCTAVIAN launches, we've reverted to expecting a GAAP net loss this year, but importantly, non-GAAP income and positive operating cash flows. And that's -- importantly, that's funding both the late-stage development assets with VOXZOGO and ROCTAVIAN and the early-stage research as well as the infrastructure of the base business. So back to the forward-looking part, it's this same infrastructure that we built that supports this $1.8 billion in revenue that should launch VOXZOGO and ROCTAVIAN, if they're approved and fund the pipeline. So while it's a transitional year, if you look at the indicators of the health of the base business and the prospects of getting leverage from that base business, we're really optimistic, and it's motivating.

And then so you talked about leverage, and you talked also, I think, about $2 billion peak or $2 billion opportunity for VOXZOGO, which, by the way, I said 5 -- at least 10 times before this call started, so I wouldn't screw it up, VOXZOGO, VOXZOGO, VOXZOGO. So what are the levers that will help those products grow? What are the key things that you need to execute on? And then how profitable are them? Like how much of your base business, how much more do you have to add to sort of -- how much leverage do you get out of the base business, I think is the next question? And then lastly, what's the ramp? Do you have a sense of what the ramp could look like? I know you probably can't give specific guidance but maybe just generalize versus other drugs that have ramped in your company. I think a lot of people view the -- in my opinion, a lot of times, people have viewed the launches of your products as sort of in line with their expectations. And so people are trying to get a sense of, could this be a quicker ramp because of the products and the profile or could this be a slower ramp.

So as I said during my introduction, the market opportunities are significant for both VOXZOGO and ROCTAVIAN. Actually each have relatively similar market sizes based on current eligibility criteria from our clinical studies, roughly 11,000 patients in EMEA and 3,000 patients in the United States. And then, of course, we can add Latin America and some Asia Pacific countries. So at the time of the CRL for ROCTAVIAN, we had a good number of people actually waiting for treatment. And longer-term data, we continue to collect with only strength and interest and uptake on ROCTAVIAN in our view. Actually based on ICER research, a $2.5 million price tag for ROCTAVIAN in the U.S. is deemed cost-effective for health care systems. So now your questions are more specific to VOXZOGO. Again, this is the first treatment option ever available that will be ever available for children with achondroplasia. So we expect BioMarin to be very interested in VOXZOGO because there is huge unmet need today when it becomes available, assuming approval. So again, market size, and I'll go back to the dynamics of the launch. So we say we expect well over $1 billion of activity here. And let's say, if you take just U.S., Europe, take 14,000 patients with, let's say, an average price between the 2 countries of close to $150,000 a year, that would translate into a $2 billion market. So it's a very large opportunity, wide open, no competition today. No competition to expect for at least 5 years as far as we can tell. So here -- compared to our previous launches, the challenges in our early business, our historical business, the enzyme replacement therapy, where ultra-orphan disorders, the challenge was to find the patients because they generally were not properly diagnosed. And sometimes it took years to find the patients. Here, the patients are very well identified. First of all, most of them, the vast majority of them are diagnosed before birth based on ultrasound. So they know -- so the patients are easily identifiable. So -- but the issue, though, is that since there is no approved therapy today, many of them, they are managed by different specialties. Some of them are managed by pediatricians because again, here we're going to be focusing on pediatric achondroplasia patients. I mean VOXZOGO will not be approved for patients over 18 years of age. So pediatric achondroplasia some of them are treated by pediatrics -- pediatricians, some of them by pediatric orthopedic surgeons, some of them are by pediatric endocrinologists, and we believe that probably the medical role of VOXZOGO is pediatric endocrinologists. And so we're going to have to make sure we connect all the patients with it -- or most of the patients with pediatric endocrinologists that can then prescribe VOXZOGO, and that could take a little while, although some of them are already connected to these physicians, so that's not going to be a problem. And then in the U.S., we would have obviously the usual early reimbursement discussions and which could take a month or 2 for some patients. And -- but the ramp should be relatively fast after that once the patients are connected to the right physician and that the reimbursement has been established. In Europe, as you know, it depends on the country. So we can go pretty fast in Germany or EMEA, I would say, Germany, Saudi Arabia, some Middle East countries, some Northern Europe countries. Other countries like France, Italy, Spain, the U.K. takes a little longer for reimbursement. But again, here, it's not going to be an issue of is there demand? Yes, there is demand. Are there identified patients? Yes, there are identified patients. It's just it's a question of getting the reimbursements in Europe more than U.S. which we believe we will get, but it just takes a little time, except for Germany. So we'll be able to launch in Germany very quickly, definitely sometime this year.

Is there like a database someone's going to have to flow through, so you have the leading indicator to help investors sort of see the people that are flowing through the bucket? Like a lot of times people have -- you call in, we help you get reimbursed, move on? Or would you...

[indiscernible] we can give you, but we're probably going to have some -- yes, like we did for Palynziq or we can probably do something similar here. Because we're going to have reimbursement support and all that. So we'll be able to know which patients are interested. And we haven't decided exactly on which metrics we're going to give you, but we will give you some metric exactly as we did for Palynziq?

All right. Then turning to Palynziq, I mean so the launch, you had that slower, slow, I want to make sure that you didn't have any anaphylaxis situations. How do you view the ramp going forward? Do you see it speeding up? Are people getting more comfortable with the drug? I mean, there's -- it seems like you barely even penetrated the U.S. market. And then the other question of do you think...

Yes. That's correct. I mean the issue has been -- the demand is there. So there are 2 available drugs preventing going faster. Actually, one, it's mainly one variable which is in the U.S., PKU clinics and actually in Europe reimbursement negotiation. So let's start with U.S. So PKU clinics are just starting to reopen the past few months because of the COVID-19 epidemic. And so now at least 50% of them -- I mean most of them are actually reopened now in the U.S. Some of them are running at a half capacity. Some of them are ramping up towards full capacity, but it is -- that is what's preventing acceleration of patient starts because the patients generally have to start under the guidance of physicians. We started program in Q4 allowing patients to actually get the first injection of Palynziq at home, but that's not very widespread yet, but hopefully, it will be in the future. But there is a real limiting factor is the PKU clinic in the U.S., but the demand is absolutely there. No question about it. Then Europe even more if you go into social media, PKU sites, you will see the amazing experiences the patients are sharing together as to the life-changing impact of Palynziq. There's no -- so that's why the demand is there. And that's why -- I mean, I think with that COVID-19 in the past year, I mean, we would have significantly more patients on Palynziq today that has been when it started up. Then in Europe, even more or ex U.S. because not only patients don't go to the clinic, haven't been, but also the COVID-19 epidemic had slowed down negotiating reimbursement price. So we're basically maybe sitting in Germany and Austria, we're starting -- about to start to sell in France and [indiscernible] in Spain, but it has delayed, we think, by almost a year, and it's all with COVID-19 epidemic, not really the product, not really the fundamental demand. And I would say in Europe, the patients that have been treated in Germany, same thing as the U.S. and you talk to clinicians and you can guide you towards our clinicians, if you're interested. They are very, very excited about the product. And they see the impact Palynziq has on the life of these patients.

So what do you think has to happen for -- it sounds like there's a huge demand, right? So if there's huge demand, I assume some patients are like getting upset, like when can I get my drug in the United States. I mean, is there going to -- do you think you're going to see like a ramp? Or do you think it's going to still be slow and steady?

There is some pent up demand. But at the end of the day, there's still the PKU clinic variable that's not going to go away. Now the good news is that, as I said, many of them don't run at full capacity yet. As most patients -- more people are vaccinated, I think this summer, things should be opening up. And actually, we are already seeing an increase in new patient starts. We are in the U.S., there's no question. But -- so the reason why we are careful on the guidance is because it's mainly regarding the ex U.S. situation. Because the ex U.S. is way behind the U.S. in terms of vaccination. And a lot of countries is still under shelter-in-place, and it is very hard to predict when things are going to open up. But in the U.S., a bit more visibility, and things are looking good.

Got it. More questions on PKU. So you have Kuvan, which is generic now, Palynziq and then BMN 307. So you are looking at all ways to treat PKU. I was just curious, we also cover a company called PTC. They have a small molecule drug that they're trying to work -- that may work in Kuvan failures. How do you see the landscape? Palynziq is still ramping. They you have a gene therapy. Then you have potential oral pill. Can you all coexist? Or one eat the revenue of the other?

Yes, let's take them one by one. So no. As I say, we believe that our PKU franchise is going to grow again next year. I mean it's mainly impacted right now by the Kuvan generics in the U.S. That's really what has slowed us down, nothing else. And it will be, of course, the COVID-19. So we anticipate to grow the market substantially and to remain the dominant player in the PKU market. Why? Because Palynziq lowers Phe levels very effectively. We can get some patients to close to normal levels with a normal diet, not all of them, but many of them. So it's way more effective than Kuvan. So if you take the drug from PTC, which I think we know very well, it's basically a poor drug of Kuvan. It's the same thing as Kuvan. I would say for them to be able to show superiority over Kuvan, it's going to be very, very difficult, that I would say that would have to do -- they would have to do a [predark] study. And I'm not even sure what would be the biological basis of doing such a study but an issue is that since it's Kuvan, it basically is a product of Kuvan. With generic competitions and pricing, I think they'll have a hard time to price this product and market because it is not as effective as Palynziq. There's no question about it. So Palynziq is, in the next 2 or 3 years, definitely going to dominate the market here in adults. And then gene therapy should kick in. A few years, we can talk about 307. We are -- we have already treated a few patients with our PKU gene therapy. So we believe that -- we see Kuvan adult transitioning to Palynziq. We see BMN 307, our PKU gene therapy, providing the path to capturing the loss to follow PKU adults because, as you know, most of the PKU adult patients today do not go regularly to PKU clinics. I would say some of them will come back and coming back for Palynziq, but it's still a complex product to get started. So for those patients, gene therapy will be great proposition because it's basically a onetime treatment or only one infusion for them should be effective for many, many years. And then you had a question on homology in terms of another gene therapy product. Yes, I would say, based on what we've heard from their communication, first of all, the highest dose that gene therapy doses treated was not -- it was barely as effective as Palynziq, probably not as effective. And we understand, maybe you know more than we do that they are winning in their dose expansion, in their pivotal trial, they're going to use a lower dose than the one that they use in the Phase IIa -- or Phase I/II trial. So we don't see it as -- even if it's not even as effective as Palynziq, I think it's going to be a little challenging to capture a lot of market share. For our own gene therapy product, we have treated already 3 patients, 2 patients at the 2e13 dose, and we already saw some significant response from the patients. We moved to 6e13. We tripled the dose. We have already treated 1 patient with that dose. We are about to treat a second patient. And based on the dose rent -- on the response, the dose response curve we saw with ROCTAVIAN moving from 2e to 6e we anticipate it's going to be a dramatic improvement in efficacy with the 6e dose. And we are shooting for fee normalization here with gene therapy. We want patients with 1 infusion to have normal Phe levels with a normal diet. And I don't see that happening with anything that's in development from our competitors today.

And then just -- it just makes me think of a question. As you talk about your -- we talked about your base business, but you talked about your pipeline, ROCTAVIAN and VOXZOGO are what everyone's focused on. But you presented a lot of that unique gene therapy capsid product that you have identified. When you guys think about the long-term value of the company, how much of it is that gene therapy division? And do you think the gene therapy, while we all right now are very nervous about the launch of gene therapy and think people are going to be skeptical in hemophilia and kind of nervous, and we've seen -- we think it's going to be challenging. Do you think that ever it's going to become as normal as getting an antibody therapeutic? I mean how are you guys -- and that's a big focus of the company. So you have to have some point of view on the long-term opportunity of that category of drugs.

Yes. We actually believe it will. I mean, again, I mean it took years for antibodies to develop. And if you remember, the very first monoclonal antibody injecting the patient, killed the patient 45 years ago -- 30 years ago. And then they were [indiscernible] I think the better self. So I think it's the same thing with gene therapy. We are at the cusp of a real therapeutic revolution here. We're already making a lot of progress ourselves. We have hired a lot of experts in vector biology, in gene constructs, understanding of the deep genetic mechanisms of the drugs that we are developing. So we're not going to turn into a pure gene therapy company, and I'm not saying that, but we believe we are -- we have the potential to continue to develop gene therapy construct that would be best-in-class or first-in-class like we believe ROCTAVIAN and our PKU gene therapy products are going to be. So at the same time, we do have in late-stage preclinical, some compounds that are not gene therapy compounds. We talked about in our Q1 call about a second-generation oligonucleotide for Duchenne muscular dystrophy, which we are very excited about. We've shown between 30% and 50% dystrophin expression in the muscles of PKU -- sorry, of a DMD mouse model that's very predictive of efficacy in humans. And we haven't seen any toxicity for the drug. We have a product -- we have a small molecule for a subset of chronic renal disorder, that's in late stage, we are -- it's actually already in the clinic now. We've treated a few healthy volunteers. And we have another molecule we haven't disclosed it. We will disclose probably at R&D Day. We see those, although a small molecule for a very exciting large offer indication, which is not gene therapy. We believe that gene therapy; however, we -- sorry, we believe that gene therapy were important, and beyond PKU, we got HAE. We signed that agreement, we did agreements with DiNAQOR to develop gene therapy for hypertrophic cardiomyopathy, which is with huge indications. It's still orphan, but a very large orphan, and that would be our biggest gene therapy opportunity. So we are definitely invested there. We have the -- today, the largest accredited manufacturing -- gene therapy manufacturing facility in the world. Our gene therapy facility in California has been inspected by Europeans, and it's approved already for setting ROCTAVIAN in Europe [indiscernible]. Brian, do you want to say something?

Yes. I was going to say so when we talk about those different modalities and then the different disease areas, there's another leverage point in there, if you will, and gene therapy is a big part of it. So you can view that gene therapy experience and know-how that we have, which includes the manufacturing and now clinical and regulatory. If you picture that as a platform, and then, yes, gene therapies in multiple diseases. And then there's a franchise perspective on leverage. So one disease space, but with multiple drug solutions. We've got that with PKU. With Kuvan and Palynziq already being approved and hopefully, BMN 307 PKU gene therapy coming behind it. And then there's a single asset, but the opportunity for multiple indications in vosoritide or VOXZOGO is the opportunity there. Where, of course, we're on file now for achondroplasia but there's a belief that vosoritide could play a role in other genetically identified short statures. So there's an investigator-sponsored study that's started up there. So that's just another way to think about these different modalities and disease areas. There is a strategy behind how we're approaching this.

Brian, can you leverage any of your excess manufacturing capacity? And you have a delay in the United States for gene therapy. Can you leverage your manufacturing facility?

Well, first of all, so we don't have -- now I'm not sure delay in Europe. So we're going to need this facility for the European launch although we have some product in inventory that we can use for that launch. And then we -- I say we got PKU gene therapy. After that, we got A3 gene therapy, potentially products coming from our DiNAQOR collaboration. So yes, we do have some short-term extra capacity for sure, but the hassle of coming up with something to feel this and that the rigidity is going to create versus what we're going to need for all the gene therapy product, it's not worth it.

Yes, but longer -- yes, so that's short term, as J.J. mentioned, but longer term, because of the gene therapy capacity that we do have, and again, this know-how, we do believe that, that does make us a partner of choice for potential collaborations, right? If you're early-stage research institution and you have an asset and you're looking for a partner that can help develop it, including manufacturing, that's where our experience can help make us a leading choice for partner. And we believe DiNAQOR is a great example of that, again, using the manufacturing platform, but a different indication and with a third party.

Got it. And I guess, Brian, I guess the question for you. There's a lot of talk at other biotech companies about shifting from a -- especially orphan disease shifting away from a ex U.S.-centric model to a U.S.-centric model because of the reimbursement situation. What is your latest point of view of that, especially since it sounds like corporate taxes could go up? And how do you feel about that? You think -- will that change your business at all?

Yes. Thanks. It's a great question. We're obviously watching that closely, both global pricing and reimbursement environment as well as taxes. I think the most important thing to note there is our business is already very diverse and very global. So 6 approved products sold globally. We sell our products in over 75 countries. We've got boots on the ground in over 50 countries. And again, back to the opening remarks, that's the infrastructure that we expect to leverage for our growth. And our patient and revenue distribution is already very global. So roughly, in 2020 our geographic revenue distribution was roughly 40% U.S. -- 45% U.S., 30% Europe and 25% Latin America, rest of world. So when we look at even the launch opportunities of the future, assuming that those launches will -- just like our prior products, will follow population and prevalence rates, we'd expect it to be roughly similar. And yes, the pricing reimbursement processes and time lines are very different, especially with the U.S. and Europe right now. But that, we believe, just means different shaped curves for revenue growth, but still the same overall opportunity. So that's how we look at sort of the growth, the geographic distribution of the growth going forward. And back to taxes, it's interesting. When you look back to the 2017 U.S. tax reform, and then over the last several years, the global BEPS initiatives of the OECD and what I refer to is global tax reform, even though it happens country-by-country in Europe, it really has worked in terms of minimizing corporate opportunities to influence their tax rate. We're seeing this already, and I think we're going to continue to see corporate effective tax rates mirror more closely statutory rates. So right now, in the U.S., with the corporate tax rate in the low 20s, we'd expect a corporate tax rate or an effective tax rate over time as our P&L matures in the low 20s. And if the Biden administration were to increase that corporate tax rate to the 28% that's discussed, we'd expect the -- our effective tax rate to drift that way. Interestingly, I don't think there's many tax accountants on the Biden speech writer team because in the 100-day remarks last week, he talked about the incentives in place for corporations to export IP out of the U.S. It's actually the opposite. There's a couple of taxes in 2017 tax reform. One is a GILTI tax. It's a penalty for exporting IP, and there's an incentive to keep it in the U.S. and sell globally, which is this FDII, foreign-derived intangible income, so that was a little incorrect. And again, the global distribution of revenue and taxes, it's really starting to level out because all these governments are working together.

So it's not as drastic as what people think. In other words, things should sort of level out a little bit and the businesses won't change as much.

It's less likely to end through end...

Well, I'm talking to finance and learning lots about taxes. One more question for you and then go back to J.J. again. So margins, you guys are turning profitable. And I think long-term guidance has sort of become out of favor amongst biotech companies. Any thoughts on that? And then when you think about margins, as you say, well, okay, you got ROCTAVIAN, you got your VOXZOGO launched. How are you thinking about how much spend you're willing to put toward R&D and business developments? Did it look different than what we've seen in the past with maybe more M&A. How are you thinking -- I guess, it's a question about BD and margins and how comfortable you are and then how you think about giving guidance.

Yes, absolutely. So importantly, we -- our plan is to do both when it comes to growing revenue and profits and continuing to fund innovation and future growth. I think we've observed out in the marketplace, other companies that may have been less aggressive with funding innovation and then your larger products start to mature or have biosimilar competition and then those companies might be -- feel the obligation to go out and make risky bets on M&A to try to buy future revenues. Our plan would be to launch VOXZOGO and ROCTAVIAN, and we discussed how large we believe those market opportunities are if they are approved. And that's where -- so the growth of revenues from those 2 larger products with the existing BioMarin infrastructure, and I mean both SG&A and R&D, we believe will drive margin improvement over time as revenue grows. And while we haven't given long-term guidance, we've talked about a goal with ROCTAVIAN, VOXZOGO and continued growth of the base business to get to roughly $5 billion in revenue by the middle of the decade. Now that might be delayed because of the ROCTAVIAN delay, but that remains the long-term goal. And we view that as the point in time where our margins -- our goal would be that our margins and our expense line items as a percentage of sales would start to look like our larger peers at that point in time. Now importantly is the R&D piece of that because right now, again, with this base business that has positive non-GAAP income and positive operating cash flows in terms of 2021 expectations, that's funding roughly $650 million of R&D. And a big portion of that R&D is what you might consider to be discretionary. It's pipeline development, not just supporting the existing business. So as revenue grows and we can afford more R&D, that's the plan to continue to fund innovation. And that's why we're doing a lot of these early-stage collaborations because these are early stage assets or hopefully the late-stage assets over the next few years. But yet, again, back to the beginning, still growing revenue and profits, but focusing on building innovation as well.

Got it. And I guess, J.J., we started off talking about big picture about your company not being valued -- I mean it's really has a value discrepancy between other companies that generate similar revenue. Maybe one of the things...

The discrepancy is the past couple of months started to dwindle, many other, can't figure it here.

Well, it's notable, right? So it's notable. And -- but as I follow you guys so long...

And as you know if I may -- actually, if I may, I mean, if you look at -- however, biotech companies with revenue over $1 billion, our market cap to sales multiple is pretty high compared to most other companies. So it depends what are you comparing ourselves with. If you compare us to biotech companies with $300 million, $400 million revenues, yes they have a higher multiple, but there is multiple compression currently when you get over $1 billion. But that as it may, please, ask your question.

I was just going to ask you about the growth. Like how do you -- investors are very fixated on ROCTAVIAN right now? Very much so. Shifting -- we'd love to shift towards VOXZOGO. We can't wait to do that. That will be exciting. But how do you...

Hopefully it will happen next month.

Next month. Okay. So all right, we'll let everyone know that next month, we will focus after EMA...

I said next month because we should get the CHMP positive opinion hopefully by the end of next month.

From EMA?

Yes.

So you've always grown products like -- because of orphan disease, they've got these really long growth trajectory, especially the base business. Do you think with the new drugs like gene therapy, for example, in VOXZOGO that that's going to happen? Or is it going to be a little bit different? You talked about VOXZOGO being more of people are more aware of the disease. They're all diagnosed. And then I assume it's like you're only on drug for a short period of time, that it would sort of flatten at some point. And with gene therapy, that's another good question because it's a one-and-done for now [indiscernible]. How do we think about growth?

Yes. So let me start with VOXZOGO -- so VOXZOGO is still I think -- the issue is still going to take several years before it peaks because, although, again, the patients -- we know the patients know they have the disorder, they are identified, they're spread around the world. And some of them, as usual, might not jump on the therapy right away. So it's going to take years for this drug -- several years for this direct to peak. And also you still also will have at the end also an incident market. So you're going to have patients that get over 16, 17 years of age get off VOXZOGO, but there are going to be some new ones coming in. So you still -- this is chronic therapy. So this is the same as our products. So we're going to keep growing for years and years, except if there is a major competition coming, which so far, it's unclear. It's at least 5 or 6 years away or if someone can figure out down the road gene therapy for achondroplasia that might be challenging, but that's going to it's going to be some years from now. So chronic therapy, loss of revenues before -- and growth before it peaks, especially also penetrating the whole world. ROCTAVIAN is different in a sense that indeed, we know we're only going to treat the patients once with ROCTAVIAN. So then you could have in the sense the peaking cells are going to be shorter, although it's going to be several years also. But also what's going to mitigate the sales peak, however, is that the initial patient population that would be eligible for ROCTAVIAN is going to be relatively small compared to the long-term population. It sounds initially we're going to start with patients with normal 85, preexisting 85 antibodies, no -- underage of 18, only severe hemophilia on prophylactic therapy. So we are life cycle management plan to actually go under 18 to treat patients with AAV antibodies down the road to treat patients with inhibitors to Factor VIII, to treat patients that are moderate hemophilia. So all this, so we're going to keep growing the market for years. Consequently also, it will take several years before ROCTAVIAN sales peak, but they will eventually definitely peak, and then there could be competition down the road. But it's going to take several years. It's not going to happen in 2, 3 years. No way.

So maybe a way to end the call because we're at the end of our time. What is the one thing you would want investors to focus on that they're not? I'm sure you're sick of getting certain questions. So refocus investors on the one thing that's most important...

I would refocus investors on the fact that more than -- close to 60% of the revenues are ex U.S. and I think unfortunately, many analysts and investors are extremely focused on the U.S., which is a small portion for us of our opportunity. They're doing so because big pharma company has more than 50% of the revenues in the U.S.

Right, they're shifting.

So I think they should shift their focus outside the U.S., on the rest, on the EUEMEA and the rest of the world. And of course, the U.S. market is extremely important. And we are absolutely planning on getting Palynziq and VOXZOGO and ROCTAVIAN approve in the U.S. But I think investors have a tendency to underestimate the size and the importance of the express market for our products.

Awesome. Well, thank you both for joining.

I mean, just to emphasize that we believe that the patient incidence and prevalence in the EUEMEA -- in our EMEA region is roughly 3x that of the U.S. for achondroplasia and severe hemophilia.

So even if you take 30% discount price to pay to the U.S. is still a huge opportunity compared to U.S. opportunity.

That's good. I've got to go work on my model.

A very exciting pipeline here. No, I mean gene therapy but beyond gene therapy, like DMD, for instance.

Awesome, well, hopefully, we can chat again about that, not over Zoom, in person.

Okay. Thanks for having us.

Thank you so much, Robyn.

All right. Thank you so much. I really appreciate it.

Bye, Robyn.

Bye-bye.

Take care.

Bye, everybody.