Biomarin Pharmaceutical Inc Q3 FY2023 Earnings Call

Hello and welcome to the BioMarin Pharmaceutical Third Quarter 2023 Conference Call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session. I will now turn the conference over to Traci McCarty, Head of Investor Relations. Please go ahead.

Thank you, JL, and thank you all for joining us today. To remind you, this non-confidential presentation contains forward-looking statements about the business prospects of BioMarin Pharmaceutical, Inc., including expectations regarding BioMarin's financial performance, commercial products, and potential future products in different areas of therapeutic research and development. Results may differ materially depending on the progress of BioMarin's product programs, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market, and developments by competitors, and factors detailed in BioMarin's filings with the Securities and Exchange Commission, such as 10-Q, 10-K and 8-K reports. On the call today from BioMarin's management team are JJ Bienaime, Chairman and Chief Executive Officer; Jeff Ajer, Executive Vice President, Chief Commercial Officer; Hank Fuchs, President, Worldwide Research and Development; Greg Guyer, Executive Vice President, Chief Technical Officer; and Brian Mueller, Executive Vice President and Chief Financial Officer. We do plan to end this call promptly at 2:30 p.m. Pacific Time, and we thank you for your understanding. I will now turn the call over to BioMarin's Chairman and CEO, JJ Bienaime.

Thank you, Traci. Good afternoon, good morning, everybody. As you will have seen this afternoon, we announced that I have decided after over 18 years with BioMarin to retire as the Chairman and Chief Executive Officer, effective December 1st of this year. As many of you are aware, I recently turned 70, and I cannot believe it myself. So it will not be a surprise to you that succession planning has been underway with the Board over the past several years. These announcements and the appointment of Alexander Hardy to succeed me as CEO follows a thorough multiyear planning process. Together with the Board, we conducted a comprehensive search over the past year, and we are thrilled to have Alexander step into the role. As part of this transition, I will also step away from my position as Chairman of the Board of Directors. However, I will continue to serve on the Board until the 2024 Annual Meeting of Stockholders, and I will stay as a consultant to the company for the remainder of 2024. I look forward to working with Alexander and the Board during this period to ensure a smooth transition. When I joined the company in May 2005, we had just one marketed product and recorded about $26 million in annual revenues. Since then, our team has developed and commercialized seven additional medicines, pioneered groundbreaking firsts, and transformed the lives of patients with complex conditions. BioMarin is now a profitable, fully integrated industry leader and one of the most successful biotech companies with annual revenues anticipated to be more than $2.4 billion this year and expected to grow to close to $3 billion next year. Our market cap has grown from around $300 million when I started as CEO to more than $15 billion today. Our stock price went from $6 when I joined as CEO 18 years ago to over $83 today at the close, generating returns greater than the XBI Index over the past one year, two years, five years, and 18 years. BioMarin is well positioned for substantial future growth and profitability. We have expanded from operating only in the United States when I started with the company with 300 employees to setting our medicines in almost 80 countries around the world and more than 3,000 employees. As the company prepares for its next phase of growth with the recent introduction of VOXZOGO and ROCTAVIAN, this is the ideal time to hand over the reins to the next leader. In the search, the Board focused on finding a successor with experience driving commercial growth and operational excellence, while also bringing a deep understanding of the science and a strong background in product development. We are confident that Alexander perfectly meets those criteria; as CEO of Genentech, Alexander led the commercialization of 10 new products in therapeutic areas, including cancer and hemophilia. Serving as CEO of this industry-leading, innovative, and impactful company over the past 18 years has been the highlight of my career. We have built an incredible organization with great potential to be further unlocked by Alexander and the team. While I will miss working with our talented and inspiring employees day in and day out, I am confident that the company is well positioned for future success. So to those on the call today, thank you for your engagement and support over the years. I want to emphasize that I will still be involved with the company, and I will still be very engaged with biotech in general, as you will find out in the future. Now let's turn back to the quarterly results. We are very pleased with the results in the third quarter, recording 15% total revenue growth compared to the third quarter last year and continued strong growth in earnings per share faster than revenue. These results were driven primarily by VOXZOGO, which remains on track to become our first blockbuster product. We saw strong demand and uptake in the quarter, and we expect this trend to continue. In the third quarter, more than 300 additional children began treatment with VOXZOGO since the end of Q2, and additional strong growth is expected in Q4. As a result, we today increased full year 2023 VOXZOGO guidance to between $435 million and $465 million. With the recent US and European approvals of VOXZOGO’s age expansions, all ages in the US and for children ages four months and older in Europe, over 1,000 additional children now have the opportunity to benefit from a longer VOXZOGO treatment window. We are also pleased to share that based on increased fill-finish manufacturing commitments, VOXZOGO supply is planned to increase from 2023 levels to the first and second quarter in 2024, and is expected to be fully unconstrained by midyear 2024. Moving on to ROCTAVIAN, we have made tremendous progress building and connecting the network that will facilitate patient treatment, laying the groundwork for our patient access to ROCTAVIAN which has taken time but has been an essential step in ensuring access and reimbursement. Well over 100 people have been tested for ROCTAVIAN and AAV5 eligibility globally, which is the first step for a patient to determine if they can be treated with ROCTAVIAN. The zero negativity rate on the samples tested to date is approximately 70%. So, 70% of the patients tested are eligible for ROCTAVIAN, but they still need to undergo a liver scan. We expect the testing momentum to continue as awareness and access increases. While it has taken more time than anticipated to wire the global healthcare system to facilitate ROCTAVIAN treatment, we remain encouraged by the high level of interest and demand from patients, physicians, patient advocacy groups, hemophilia treatment centers, and payers. In Europe, we made strong progress in the quarter and expect to have final German and Italian prices for ROCTAVIAN published by year-end. In the US, significant momentum connecting the network to treatment is occurring. Jeff will provide more detail on launch progress and our updated expectations for ROCTAVIAN. In conclusion, we have built an industry-leading company. The strategy to create a sustainably profitable and growing business that provides patients with innovative and essential medicines is coming to fruition. The future looks very bright for BioMarin, and I want to thank my colleagues for the tremendous collaboration we have built together.

Thank you, JJ. I'm very pleased with our commercial performance in the third quarter, resulting in $581 million in total revenues and representing 15% growth year-over-year, including KUVAN and 20% growth excluding KUVAN. Turning to VOXZOGO, as JJ mentioned, today we updated full year guidance to between $435 million and $455 million, representing approximately 165% year-over-year growth at the midpoint. Appreciating that the run rate for the fourth quarter and full year 2023 may seem conservative based on VOXZOGO revenues of $123 million in the third quarter, we note that the impact from supply constraints discussed last quarter continue to limit growth through the end of this year. While we continue to closely manage new patient growth and limit inventory stocking, we expect to fulfill smaller orders from various regions in Q4, while at the same time adding hundreds of new patients. As a reminder, new patient starts with VOXZOGO in the fourth quarter will represent only a fraction of a full year revenue patient in 2023. Importantly, we expect approximately 2,600 patients to be receiving VOXZOGO treatment by year-end 2023. VOXZOGO supply is planned to increase from 2023 levels through the first and second quarters of 2024 and is expected to be fully unconstrained by mid-year next year. At the end of the third quarter, more than 2,300 children with achondroplasia in 38 markets were being treated with VOXZOGO. Uptake to date represents 12% penetration of indicated patients in BioMarin's commercial footprint, highlighting the significant growth potential remaining. With the opportunity now to treat up to an additional 1,000 children following the recent age expansion approvals in the US and Europe, we look forward to the possibility of the youngest children in these regions benefiting from VOXZOGO therapy. Turning now to ROCTAVIAN. We are pleased to share that the second commercial patient was treated today in Germany. As JJ highlighted, we continue to make progress connecting the network that will facilitate treatment. 2023 has turned out to be the year of building that network to ensure and support meaningful patient uptake in 2024. Starting with Europe, we have a tentative agreement with the German National Association of statutory health insurance funds on the final German price for ROCTAVIAN, which we expect to be formalized and published by the end of the year. We believe that this important step, given the unique treatment and reimbursement profile of ROCTAVIAN, will open up the access funnel with treatment in Germany. We are pleased to share that in Germany, 60 people are known to be eligible based on CDx testing for AAV5 antibodies. The vast majority of those are in follow-up for next steps. As expected, the seronegativity rate of about 70% is in line with our steady results and consistent with expectations. We are also pleased to report that there are now 10 sites in Germany testing for eligibility. For the large pool of eligible patients and the final German price expected to be published soon, we are optimistic about patient uptake rates in 2024. Important to note is that the first patient treated resulted in net revenue of approximately $800,000. Gross-to-net revenue adjustments going forward under the GKV agreement will be different from the first patient reported, but our overall expectations are to maintain similar net revenue per patient in Germany, noting the impact of weight-based dosing and variable weight of patients. In Italy, negotiations with the Italian Medicines Agency are going well, and we expect to have a final price published by year-end. Italy represents our second major European market that has agreement on price and reimbursement, opening the door to ROCTAVIAN access likely in early 2024. We continue to work with the authorities in France and expect pricing negotiations to extend into 2024. It has taken several months in the US following approval to align stakeholders and to facilitate first patients treated. This is a result of the unique profile of one-time reimbursement and treatment with ROCTAVIAN. Navigating hospital administration and finance adds a level of complexity for hemophilia treatment centers, leading to the final step of patient treatment with ROCTAVIAN. We expect that these administrative steps taken at the HTC level, while time-consuming, are one-time events and essential to facilitate patient access going forward. In short, the groundwork completed in 2023 is expected to enable simplified access to ROCTAVIAN, drive more AAV5 eligibility testing, and give us confidence in the prospects for 2024. However, we're less than two months remaining in the year, and with the holiday season beginning soon, we are lowering full year ROCTAVIAN 2023 guidance to less than $10 million. Moving now to the specific steps completed this quarter, starting with the issuance of coverage policies across payers, both private and public, we are pleased to share that nearly two-thirds of all covered lives in the United States have been issued coverage policies to date, representing approximately 205 million people. Importantly, the vast majority are in line with label or clinical trial criteria and are thus favorable in meeting expectations. Additionally, we are encouraged by the rapid uptake of the outcomes-based warranty with signed warranties in place representing more than 95 million US lives. We have also received notice that the J-code for ROCTAVIAN has been assigned effective January 1, 2024. The permanent J-code is expected to accelerate payers' prior authorization review process, ultimately speeding time to patient treatment. Taken together, these developments are a strong indication of the value that the US health system places on a cost-effective one-time gene therapy. As we stated in our approval in the Q2 earnings call, we expect it could take patients two to five months to complete the steps necessary before treatment with ROCTAVIAN. The commercial team has been hard at work implementing a number of tactics to prepare physicians, HTCs, and patients for the opportunity to benefit from ROCTAVIAN. With respect to site readiness, HTCs are being prepared and educated on how to administer ROCTAVIAN. We have targeted the largest and most capable HTCs for site readiness by year-end, many of which have readiness plans before the end of this year. Increasing HCP and patient awareness in the US was also an important focus in the quarter. A number of activities were conducted, including national HCP and patient webinars and the third annual Global Gene Therapy Scientific Summit sponsored by BioMarin. We are especially encouraged by the number of local patient advocacy groups that have been willing to host branded patient awareness programs for ROCTAVIAN. Medical eligibility, including CDx testing is underway. As a result, the US patient funnel is beginning to take shape, giving us confidence in the prospects for treating patients going forward. In conclusion, we are on track to achieve full year total revenue guidance driven by the strength of our inside product revenues and continued high demand for VOXZOGO globally. Looking ahead, we believe the network built to facilitate treatment with ROCTAVIAN, combined with our high expectations for VOXZOGO and strong enzyme business, will enable BioMarin to approach close to $3 billion in total revenues in 2024. Thank you for your attention, and I will now turn the call over to Hank to provide an R&D update.

Thanks, Jeff. Thank you, JJ. The privilege has been ours, and thank you all for joining us today. We provided a thorough update on our earlier stage pipeline at R&D Day in September. If you missed it, please find the full presentation on BioMarin's IR website. Starting with VOXZOGO in the quarter and shortly beyond, we received some important updates from global health authorities resulting in expanded access to younger children in both the US, where it is now approved in all age groups, and in Europe for children four months of age and older. We're gratified that the youngest children now have the possibility of greater potential long-term benefits from treatment with VOXZOGO. I want to thank not just the usual clinical and regulatory teams at these finish line efforts, but also the extended BioMarin team of safety professionals, biometrics professionals, operations, pharmacology—really, the whole entire fully integrated team played a strong role in enabling this advancement and access to patients. On behalf of the families and children with achondroplasia, thank you all. As mentioned last quarter, we have solidified our plans to begin the pivotal program using VOXZOGO for the treatment of hypochondroplasia, with a natural history arm of the study expected to begin this quarter. The pathogenesis and epidemiology are similar between achondroplasia and hypochondroplasia. While hypochondroplasia presents with a milder phenotype in some patients in terms of short stature and clinical manifestations, we plan to target the population with the most severe form of the disease and the highest unmet need with high deficits beyond three standard deviations below the means. With alignment from the FDA on a single registration enabling a 52-week randomized double-blind placebo-controlled study with a primary outcome of annualized growth velocity, we look forward to initiating the treatment arm of the study in 2024 following the natural history running portion. Additionally, we plan to initiate two new clinical programs next year with VOXZOGO, one in idiopathic or polygenic short stature and the other in defined genetic short stature conditions. We know that CNP is a pivotal physiological stimulator of endochondral bone growth at the level of the growth plate. Further, human genetic studies of CNP, not FGFR3, demonstrate that even modest nudges in CNP signaling have a significant impact on final adult height. This supports our confidence that VOXZOGO can deliver transformational improvements in growth across many forms of skeletal impairment while retaining the strong safety profile demonstrated in achondroplasia. For these reasons, we look forward to starting the clinical programs in these additional statural indications in 2024. Please take a look at the full R&D Day presentation for the latest update on our seven portfolio candidates discussed in September, and we look forward to keeping you apprised as they progress through development. Thanks for your support, and I'll turn the call over to Brian to update financial results in the quarter.

Thank you, Hank, and thank you, JJ, as well. Please refer to today's press release, summarizing our financial results for full details on the third quarter of 2023. Since JJ and Jeff spoke to our revenue performance for the quarter and future revenue outlook, I will primarily focus on the remainder of our P&L and other key financial updates this quarter. As usual, all results will be available in our upcoming Form 10-Q, which we expect to file tomorrow. We are pleased with our year-to-date revenue growth of 14% and non-GAAP earnings per share growth of 33%, which well positions us to achieve our top and bottom line financial objectives in 2023, as indicated by our narrowed guidance provided today on total revenue and earnings per share. As underscored in today's guidance updates, we continue to expect double-digit revenue growth coupled with meaningful P&L leverage with GAAP and non-GAAP earnings per share growth faster than revenue. Moving on to Q3 results, BioMarin’s $581 million of total revenue in the third quarter of 2023 grew 15% compared to the third quarter of 2022 and 19% on a constant currency basis. VOXZOGO's strong performance and healthy growth in the enzyme products marketed by BioMarin drove this result, with some partial offsets of lower KUVAN revenue due to continued generic competition and Aldurazyme timing of order fulfillment to Sanofi. The strength of our portfolio consisting of eight commercial products allows us continued patience on the pioneering nature of the ROCTAVIAN launch. Specifically, we are able to maintain our original full year 2023 total revenue growth expectations, which represent 16% year-over-year growth at the midpoint, and our implied Q4 2023 growth rate at the guidance midpoint of over 20%. We remain confident in the long-term prospects of ROCTAVIAN and its potential to drive growth in 2024. Regarding gross margin, Q3 2023 gross margin of 78.5% is an improvement of 1.6 percentage points as compared to the third quarter of 2022. R&D expense in Q3 2023 was $191 million, and SG&A expense was $224 million, which combined totaled $415 million and grew 11% versus last year. Compared to 15% revenue growth in the quarter, this aligns with our goal of growing operating expenses slower than revenue to deliver operating margin expansion for the full year. The increase in R&D and SG&A was primarily driven by the development of our early-stage pipeline and global commercial launch activities for VOXZOGO and ROCTAVIAN. As we look ahead to the fourth quarter, we anticipate that total SG&A and R&D expense will be higher than Q3 on a dollar basis due to the same drivers. Moving down the P&L, we continue to see an increase in interest income due to higher yields on our cash and investments. On tax expense for the quarter, I will note that we recognized tax expense at a lower effective rate during Q3 due to some discrete tax benefits during the quarter. This lower tax expense in Q3 will likely modestly benefit the full year tax as well, but we continue to project our global annual effective tax rate will be in the 20% to 23% range over the next few years. On the bottom line, we delivered on our commitment to profitability with $40 million of GAAP net income in Q3 and $89.5 million of non-GAAP income. This level of profitability for Q3 and year-to-date gives us confidence to achieve our stated objectives of sustained and growing profitability on a full year basis going forward. Year-to-date, 2023 non-GAAP diluted earnings per share has increased 33% compared to Q3 year-to-date last year, and today we have reaffirmed our midpoint guidance for non-GAAP diluted earnings per share for the full year. In closing, we are on track to meet our top line and bottom line objectives for 2023 and beyond with strong double-digit growth in both revenue and profitability. The continued success of VOXZOGO, the momentum building for ROCTAVIAN and ongoing margin expansion efforts give BioMarin a strong foundation to achieve our financial goal of being one of the industry leaders in revenue growth and margin expansion as we close 2023 and head into 2024. Thank you for your attention, and we will now open up the call for questions.

Thank you. Your first question comes from the line of Salveen Richter of Goldman Sachs. Your line is open.

Good afternoon. Thanks for taking my question. And JJ, it's been a pleasure working with you. Good luck on the next venture here. With regard to my question, you talked about the ROCTAVIAN, the HTC preparedness that's required? And then you also provided some context of two to five months to prepare patients for treatment. Can you just break that down for us, like the time period needed for HTC, then kind of the payer dynamics that will play out the diagnostic aspect as well? And how demand is stacking up as you get a sense from physicians and lease centers right now? Thank you.

Hey Salveen, I'll take a shot at that one. There's a lot of moving parts in this launch. There is the specific HTC dynamic which is not unique to ROCTAVIAN. So, you may be getting some insights into how that's playing out in a parallel launch in the United States. The HTCs need to be prepared both for the administration of a one-time treatment with ROCTAVIAN, which includes handling a frozen product, a very high-value item. It includes other dynamics like 340B discounting and pricing, relative in some cases to larger healthcare systems that may have some capabilities that the HTC does or does not have. So, there are various dynamics inside of the HTC. There's also the payer dynamics occurring, which would be expected in the United States. But in this case, the payer dynamics are complicated by the fact that gene therapies as high-value, one-time treatments are new and different. We’ve expected the payers to take some time to understand that issue for years and have been preparing for that eventuality. There’s also patient awareness and interest in a highly competitive and dynamic changing standard-of-care environment. There are physicians that have a number of options available to them. There are all those dynamics going on in parallel, and we're navigating all of those issues. Some are taking more time. I think the two-thirds of the US population with issued coverage policies four months after approval is encouraging and very fast. The uptake of the warranties at the levels described is very fast and very encouraging. We're seeing the patient funnel now starting to shape in the US. I've been describing that patient funnel in Germany, and the US patient population is substantially larger than that of Germany. However, early signals in the US look like the patient funnel is going to take shape similarly to what we've experienced in the US, giving me a great deal of confidence that as we finish up this year, hopefully treat some patients in Q4. I am quite confident that connections with payers and the dynamics in the United States are falling into place, all indicating greater uptake in 2024. Thanks for the question.

Your next question comes from the line of Geoff Meacham of Bank of America. Your line is open.

Great. Hey, guys. Thanks for the question. JJ also wanted to offer up congrats on the retirement. So, not surprisingly, I have a few on ROCTAVIAN as well. So, the first one is, I know you're not giving more detailed '24 guidance than the $3 billion in revenue, but at a high level, how would you characterize the ROCTAVIAN contribution? And the second question is, I guess when you use Germany as a proxy, you have 60 patients that are pretty late in the onboarding process. It's been on the market officially for over a year. Is there – is there what you would characterize as a second wave or is the 60 mostly hit? I wasn't sure kind of if there's a bit of a ripple effect once you get formal reimbursement? Thank you.

Hey, Geoff, Brian here. I'll start with first question. On the $3 billion, as you noted, we haven't given specifics behind that. We'll plan on doing that early next year, like we typically would. But importantly, there's continuous growth in VOXZOGO over '23 and a meaningful contribution from ROCTAVIAN. So I'll ask you to stay tuned for the details. You understand what has been the typical growth trajectory for the mature enzyme products, and still growing healthily here, plus substantial growth in VOXZOGO, plus meaningful ROCTAVIAN contribution gets us to that approximately or approaching $3 billion.

As usual, we will provide more detailed guidance when we report Q4 in February of next year.

Great question about the 60 AAV5 eligible patients that have yet to be treated in Germany. The pace of CDx testing in Germany has slowed down over the summer, reflecting both the general slowdown in August and the fact that some of our earlier plans to treat patients in the free pricing period while negotiating with GKV weren't paying out as hoped. So, we know the HTCs were slowing down in Germany waiting for the GKV process to be finished. My perception is a pickup following the end of summer in CDx activity and lining up patients to be treated in Germany reflects both getting past summer and an expectation that these HTCs know that we've concluded the price negotiations. They're just waiting for the price to be published to move ahead with patient treatment. In Germany, the physicians and data on other launches suggest that Germany moves slowly for adoption of new hemophilia options. Having 60 patients in Germany that are AAV5 eligible would equate to about 240 to 250 patients in the United States on a population-adjusted basis. So, just benchmarking what may be the possibilities in the US. Thank you.

Your next question comes from the line of Phil Nadeau of TD Cowen. Your line is open.

Good evening. Thanks for taking our questions. JJ, let me add our congratulations on a very successful tenure and your retirement from BioMarin. Again, a couple of follow-ups on ROCTAVIAN, specifically on patient demand. On the last earnings call, you mentioned that patient consent forms had been trending well and that BioMarin was happy with the rate they're coming in. Any update on how patient consent forms are trending, and is there any visibility on when the first US patients could be treated? That's question one. And then question two, in terms of the institutional challenges, we've had some physicians mention things like training staff, beds need to be set up, and equipment needs to be ordered. Are those challenges at the HTCs, and if so, is there anything BioMarin can do to remove those bottlenecks? Thanks.

Thank you for the question, Phil. So, let me address the second point first, regarding the institutional challenges. In the prepared remarks, I addressed HTC site readiness and some elements that are one-time events that won’t be recurring. The types of challenges you mentioned are generally captured in that HTC site readiness and institutional preparations for ROCTAVIAN treatment, taking a little bit of time, which should be resolved and facilitate patients moving expeditiously through those types of challenges going forward. In terms of patient demand in the United States, we’re not disclosing patient level details, but we’re encouraged by what we're seeing so far. In the United States, we have this hub operation, and historically, all patients move through our hub first before moving through the next steps toward treatment. Given the nature of the HTCs and their capabilities, we’ve been seeing patients come into our hub later in the process rather than at the very beginning. We’re working to understand this dynamic better, but yes, we are upbeat about the patient demand and the funnel building up in the United States.

In addition to the funnel building up, it is possible we could treat some US patients by year-end. I would say we have three US patients who have now cleared all ROCTAVIAN screens for treatment, including AAV5, liver scan, liver health, and all that. While the timing of their treatment isn't guaranteed in '23, they have completed all eligibility testing for treatment, so it is very likely to occur in the near future.

Your next question comes from the line of Robyn Karnauskas of Truist. Your line is open.

Great. I have three quick questions. Number one, JJ, you have mentored so many people on the street, and we appreciate that. Is Hank retiring too? We would have a panic attack if that’s happening, so maybe an announcement on that would be great. Is Tracy getting a promotion? That's our first question. The second question would be about ROCTAVIAN. There was such a focus, and you misguided this year on the outcome of what you could achieve. Do you think in 2024 you can do better? Lastly, I think on VOXZOGO, that came away from our analyst meeting as the big takeaway. How do you think about communicating the opportunity there and the timelines for that? I’ll leave it with that.

Thank you, Robyn. I mean, I think there was a previous question regarding ROCTAVIAN and a detailed answer from Geoff. Indeed, it took longer than we anticipated to connect the patient with the treatment centers. So, again, big picture, when you have such a high-cost item like ROCTAVIAN at $3 million, it attracts a lot of interest. Since it is a significant investment, people want to ensure that everything is aligned to proceed with the treatment. Just to note, many hemophilia patients in the US are statutory and 340B patients. Considering the value of such a therapy, the interest will remain high. That said, we believe ROCTAVIAN has great potential and will be a significant contributor in 2024 and beyond, especially as we expect constraints to ease significantly in the near term.

Your next question comes from the line of Joseph Schwartz of Leerink Partners. Your line is open.

Great. Thanks very much, and best wishes to JJ. That's really the end of an era. So, I guess I was wondering if you can help us understand what kinds of initiatives you've undertaken to address the administrative delays and site readiness issues, and what kinds of success have you had where you have implemented these things. Also, what initiatives do you have left to implement to support ROCTAVIAN's growth? Any more color there would be very helpful.

Thanks, Joe, for your question. The administrative delays have largely dealt with the mechanics of providing scientific support to HTCs, physicians, and patient advocacy groups, including local chapter events. We focus on working on the ground with our teams to keep those processes moving despite the little challenges that are popping up. The challenges are mostly one-time events. It's about maintaining and ensuring the appropriate support and communication to support ROCTAVIAN’s growth.

Regarding Germany, in Europe, patients do not pay for drugs or doctor's visits. The key thing in Europe is to have official government reimbursement. That is about to happen in Germany and Italy. As we've mentioned, we already have an agreement on the price in Germany. We now need to publish that price, which should occur over the next few weeks. Once that happens, there should be no barriers left in Germany because the majority of eligible patients are very likely to be treated.

Your next question comes from the line of Chris Raymond of Piper Sandler. Your line is open.

Thanks, and congrats from us too, to JJ, and sorry to see you leave. I've got two questions, maybe one a commercial one for Jeff and then one for Hank, if that's okay. So, maybe just on VOXZOGO, Jeff, could you talk a little about the triage process that you've instituted with new patient starts? What retention programs do you have in place for those new patients who want to be on therapy but can't? Can you give us a sense of that number now, and where you expect it to grow to when you get back up to supply mid-next year? And then on the R&D side, Hank, I noticed back at your R&D day, your cardiomyopathy programs, 293 was supposed to have its initial data proof of concept in 2025, and 365 was the year after. It looks like those have been pushed a year. What’s happening there?

Thanks, Chris. So, regarding VOXZOGO, we anticipated that by early 2023, we would reach a point where we could not satisfy all patient demand. Our objective during the year has been two-fold: to ensure continuity of supply for patients already on VOXZOGO while minimizing risk for new patients who may start therapy where we cannot assure ongoing supply. We’re working to project patient demand across our 38 markets. By managing this process closely, we have strategically delayed our entry into certain markets until we can assure treatment continuity. We’ve reached a point where there are patients in some markets that we are attempting not to begin treatment if we cannot guarantee ongoing supply. This process is designed to minimize disruptive changes for patients once they’re started on therapy.

To clarify, as we move towards the second half of next year, we expect significant patient numbers to be supported through the increased supply and inventory, which translates into a substantial uplift in patient numbers in the first half of next year.

Regarding your question about earlier stage programs shifting, they haven’t shifted in their advancement timelines. As part of our ongoing efforts to streamline communications, we’ll provide updates to the street when we reach clinical proof of concept. So the timing of those communications is what’s changed, not the actual advancement.

Your next question comes from the line of Paul Matteis of Stifel. Your line is open.

Thanks so much, and I'll add my congrats to JJ as well. I was curious, during the CEO search and succession planning over the past couple of years, what were the two to three key priorities? How important was it for a new CEO to stay the course on BioMarin's core strategy over the past few years, and what are the chances that Alexander Hardy will enact material changes over the next 6 to 12 months that could make BioMarin look different?

Yes. In our comprehensive search, we prioritized several key factors, including leadership ability, a successful track record of growth, and an understanding of the science behind therapeutics. Alexander has demonstrated an ability to deliver and grow business as CEO of Genentech. We believe he has what it takes to steer BioMarin toward continued growth. Alexander will assess the situation and determine what needs to change, if anything. We're looking forward to collaborating with him and have confidence in his capabilities.

Your next question comes from the line of Akash Tewari of Jefferies. Your line is open.

Hi, thanks for taking our questions. This is Ivy for Akash. And JJ, congrats on the retirement. I have a question about the cadence of new patients added next year for both the US and ex-US. With the expected $3 billion contribution from ROCTAVIAN, which looks quite high compared to the guidance you have for this year. What needs to happen to hit that target? Is this a fair target to discuss? If you break down the $4 billion to $5 billion mid-decade revenue target, how much of it is expected to come from VOXZOGO and how much from ROCTAVIAN?

I'll start with the overview of revenues. As we touched on earlier, the key takeaway from the approaching $3 billion revenue expectation for 2024 is that ROCTAVIAN is expected to come online globally, primarily in Germany and the US. The challenges and delays discussed this year should mostly be timing-related. Jeff has mentioned positive momentum recently coming together; patient interest, physician interest, the site readiness, contracting, and reimbursement are crucial elements required for patients to come online. We anticipate significant progress throughout the coming months, which will contribute to the revenue growth. There are no changes to the $4 billion to $5 billion target, which we believe will consist of about half from the base business and half from VOXTOGO and ROCTAVIAN.

I think we refer you to some answers regarding this before. Thank you for your patience.

Your last question comes from the line of Jessica Fye of JPMorgan. Your line is open.

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 talk qualitatively about the geographic mix of VOXZOGO sales? Which regions or countries have the most growth left in front of them in achondroplasia?

I don't think we're disclosing market-level detail, but overall I mentioned that there’s 12% patient penetration of the indicated patient population, including those recently opened ages in the US and four months and up in Europe. There is sizable variability in uptake, with early rapid uptake in places like Germany and Japan having raised penetration rates. However, in other areas, such as the United States, which recently opened up a very young patient population with strong treatment value potential, we see considerable room for increase in penetration.

There are no further questions at this time. I'll now turn the call over to JJ Bienaime, Chairman and CEO.

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.

This concludes today's conference call. You may now disconnect.