Q – Unidentified Analyst: Hi, thanks for taking our questions. This is Ivy for Akash. And JJ, congrats on the retirement. The former question, so I guess for 2024, I know you haven’t given any product specific details for – what will be the cadence of new patients add next year for both US and ex-US, because consumers right now has 350 million contribution from ROCTAVIAN, which looks quite high compared to the below 10 guidance you have for this year. So what do you think needs to happen to hit that target? Or is that like a fair target to say? And secondly, I think it’s for your mid-decade rev go off around $4 billion to $5 billion. Are there any updated thoughts to that target? And if you are to breakdown this $5 billion by product, how much of it is from VOXZOGO? And how much of it is from ROCTAVIAN? Thanks.
Brian Mueller: I’ll start with the big picture, revenue questions. This is Brian then Jeff can maybe touch on the cadence briefly. So I touched on this a little bit in Jeff’s question earlier. The key take away from the approaching $3 billion revenue expectation for 2024 is that ROCTAVIAN is expected to come online globally, mostly Germany and US. And the challenges and delays that we’ve discussed for 2023 in the context of 2024, we expect to be timing. Jeff and JJ touched on the German price dynamics. We’ve got the patient funnel filling up with what we believe to be the final gate, which is concluding the price and getting the publication in the National Register. That should open up that pool of patients for 2024. In the US, Jeff on a couple of the answers has talked about these dynamics that are coming together, positive momentum.
But that’s why we use the terminology network to bring all those pieces together. Patient, physician interest, site readiness, contracting, and reimbursement, they all need to come together to have patients come online. That’s taken longer in 2023, but we expect to be making significant progress over the next few months where we’ll start to see those patients come online in ’24. So the key take away from that $3 billion is that there is a meaningful piece of ROCTAVIAN there, which is a bridge from where we’re at in ’23. And then briefly, no changes to the $4 billion to $5 billion, obviously, we need to continue to monitor and execute on both VOXZOGO and ROCTAVIAN. We’ve commented previously that that $4 billion to $5 billion is roughly made up of half of the base business with continued growth and half of ROCTAVIAN and VOXZOGO.
Jean-Jacques Bienaime: But I think we refer you to some comments – answers to questions that we had previously on the call that should address your questions, because they were asked earlier. Sorry, we’re running out of time.
Operator: Your next question comes from Jessica Fye of JPMorgan. Your line is open.
Jessica Fye: Hey, guys. Thanks for taking my question, and JJ best wishes for your retirement. Recognizing what you’re doing to manage supply with VOXZOGO, can you just talk qualitatively about the geographic mix of VOXZOGO sales, and which regions or countries have the most growth left in front of them in achondroplasia?
Jeffrey Ajer: Yeah, I don’t think that we’re disclosing market level detail, Jess, but overall mentioned that there were 12% patient penetrated of the indicated patient population, which includes the four months and up in Europe and from birth, essentially, in the United States. There is some variability in uptake. I think I mentioned previously that early rapid uptake in places like Germany and Japan leave them at a relatively higher penetration rate, so far without ceilings, but a higher rate in other places, importantly, like the United States, which just had a huge expansion of the patient population open to us. That patient population, very young patients having the strongest value proposition for treatment opens up a lot of penetration room in the United States, for example, probably too much detail to get into for other markets.
Operator: And your last question comes from the line of Ellie Merle of UBS. Your line is open.
Ellie Merle: Hey, guys. Thanks so much for squeezing me in. Just in terms of the VOXZOGO expansion studies, from a disease biology perspective, how should we think about the potential mechanistically for CNP to expand into other indications relative to FGFR inhibitors? I guess, are there indications where you think the biology might make more sense for CNP and not FGFR or vice versa, or where you think CNP is particularly likely to be active? Thanks.
Jeffrey Ajer: Blessings on you, Ellie, for asking the question, so that I could both say unequivocally to Robin’s earlier question, I’m here and very committed to BioMarin. And partly for exactly this reason, I think that when you look at the genetics of statural impairments, and our group has actually published quite nicely on this, that gain-of-function mutations in CNP confer a high benefit, loss-of-function mutations, convey short stature across a polygenic background. That, I think, is very strong evidence that CNP is going to be a dominant regulator of bone growth. Interestingly, you can find loss of function or – sorry, gain of function variants in FGFR3 when they are associated with stature. They’re also associated with profound other abnormalities.
So that’s why we think that the CNP axis is going to be the perfect target for improving stature across a wide range of both genetic and polygenic indications, and why FGFR3 approaches are primarily going to be limited to FGFR3 abnormalities. You can get a lot of height benefit nudging the CNP axis safely. You have to hit the FGF axis quite hard in non-FGF indications and probably too toxic effect. At least that’s based on human genetic data. So thanks for the question. We’re very excited about that future.
Operator: There are no further questions at this time. I’ll now turn the call over to JJ Bienaime, Chairman and CEO.
Jean-Jacques Bienaime: Thank you, operator, and thank you all for joining us today. We are pleased with our results this quarter and our prospects ahead. BioMarin is now a profitable, fully integrated industry leader with annual revenues well over $2 billion and is extremely well positioned for substantial future growth and profitability. Thank you for your continued support and have a good afternoon or evening.
Operator: This concludes today’s conference call. You may now disconnect.
