Earnings Call Transcript - BMRN Q2 2022

Operator, Operator

Welcome to the BioMarin Second Quarter 2022 Financial Results Conference Call. Hosting the conference call today from BioMarin is Traci McCarty, Group Vice President of Investor Relations. Please go ahead, Traci.

Traci McCarty, Group Vice President of Investor Relations

Thank you, Rob. Thank you, everyone, for joining us today. To remind you, this nonconfidential 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, along with the 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 from BioMarin's management team today are J.J. Bienaime, Chairman and Chief Executive Officer; Jeff Ajer, Executive Vice President and Chief Commercial Officer; Hank Fuchs, President Worldwide Research and Development; Greg Guyer, Executive Vice President and Chief Technical Officer; and Brian Mueller, Executive Vice President and Chief Financial Officer. I will now turn the call over to BioMarin's Chairman and CEO, J.J. Bienaime.

J.J. Bienaime, Chairman and CEO

Thank you, Traci, and good afternoon, everyone. Thank you for joining us today on the call. So the first half of '22 is our strongest six-month results to date with over $1 billion in combined total revenues from our record-breaking first and second quarters. VOXZOGO revenues of $54 million in the first half of the year contributed to these results, and they were driven by the continued rapid expansion of global commercial access for our treatment of achondroplasia. VOXZOGO growth led to today's increase in top and bottom line guidance for the full year, despite ongoing economic challenges, including considerable foreign currency exchange rate fluctuations and the strength of the dollar. Turning now to some of the key highlights in the second quarter, all of which were first in our industry. In late June, we were thrilled to have received a positive CHMP opinion for Europe for ROCTAVIAN. We continue to expect European Commission approvals in the third quarter, which will be opening access to thousands of people with severe hemophilia who are interested in a one-time infusion of ROCTAVIAN gene therapy. This will be the first gene therapy to treat any hemophilia recommended for approval in Europe. Jeff and his team are ready to launch ROCTAVIAN upon potential EC approval later this quarter. In the U.S., we remain on track to resubmit the BLA by the end of September, the end of next month. Another first is the approval of VOXZOGO in Japan for children of all ages with achondroplasia and no age restriction. This approval represents our largest commercial opportunity today in Japan, and we look forward to working closely with the achondroplasia community there. We also received approval in Australia for children ages 2 years and older. These important additions to the global access footprint are expected to generate meaningful revenues throughout Japan beginning later this year. With BioMarin's financial outlook and robust global launch of VOXZOGO tracking to plan and ROCTAVIAN approval on the horizon in Europe, we are on our way to achieving the goals set forth at the start of the year. Turning the quarter to sustainable GAAP profitability, ramping up our largest opportunity today with VOXZOGO, and then progressing ROCTAVIAN to approval in Europe and pursuing approval in the U.S. and also advancing the broadest early-stage pipeline in our history. I would add that as compared to where we were a year ago, we have made major progress to substantially reduce regulatory risk for BioMarin with the global approval of VOXZOGO and upcoming approval of ROCTAVIAN in Europe. We will continue to build on this financial, commercial, and regulatory momentum in the second half of 2022 and beyond as we make the transition to an earnings call story. Thank you for your continued support. We’ll now turn the call over to Jeff to discuss the commercial business update.

Jeff Ajer, Executive Vice President and Chief Commercial Officer

Thank you, J.J. I'm very pleased with our record performance in the second quarter of 2022, resulting in $534 million in total revenues, which represents a 6% growth year-over-year, including Kuvan, and 13% growth, excluding Kuvan, which continues to experience decreasing market share. Year-to-date, all brands marketed by BioMarin, with the exception of Kuvan, experienced revenue growth year-over-year. Starting with VOXZOGO, we are pleased to share that as of June 30, 2022, an estimated 446 children were being treated with commercial VOXZOGO. This includes 282 children in countries outside of the United States and 164 children within the United States. At the end of the second quarter, VOXZOGO sales were spread across 20 active markets, including sales in new markets like Brazil, China, Hong Kong, Qatar, and Russia. Outside of the EU, we are thrilled to have received approvals in Japan and Australia during the second quarter, giving us a strong foothold in the Asia-Pacific region with revenue contributions expected to begin later this year. Regarding launch dynamics in the United States, we continue to see prescription demand ramp up. We have been able to rapidly convert patient referrals to patient starts, with prescriptions primarily coming from genetics and pediatric endocrinologists. As expected, we are making continued progress in creating the referral pathway to pediatric endocrinologists. We also see more payer coverage policies published that are largely consistent with our label and our clinical trials criteria and aligned with our expectations. We also continue to experience patient growth in European markets consistent with what we have seen in the previous quarter, including new patients from new markets. As a result of the strong VOXZOGO ramp, we are increasing full year guidance once again to between $130 million and $160 million for the full year 2022. In summary, for VOXZOGO, we are very pleased with the pace of uptake during the first half of this year and note that we are well into the global launch cascade of VOXZOGO. These results underscore the ability of our experienced commercial teams to tap into large market opportunities regardless of location. Launching in the EMEA region, ahead of the United States, provides the team an important framework for a potential ROCTAVIAN launch in the coming months, should the European decision be supportive. Turning now to our enzyme replacement therapy brands, we collectively achieved record results in the first half of the year, with Q2 sales lower than Q1 due to the volume of large irregular orders placed in Q1. This is consistent with our experience of uneven quarterly revenue patterns, particularly for Naglazyme and Vimizim. In 2022, we expect a higher concentration of revenues in the first half of the year compared to the second half. Our expectations for the full year are reflected in today's updated guidance, where we have narrowed the range for both Vimizim and Naglazyme and increased the top of the range of Naglazyme by $10 million for the full year. For Brineura, 24% growth year-over-year and revenue of $38 million in the second quarter was driven by 18% growth in commercial patients compared to a year ago. Renewal guidance remains unchanged. Moving now to Palynziq. Net product revenues grew 4% to $62 million in the second quarter compared to the second quarter of 2021. While we expect meaningful year-over-year growth and saw continued net patient growth in the quarter, Palynziq's performance trailed our expectations, resulting in an adjustment to full year guidance downward to between $250 million and $275 million. We expect Palynziq patient trends to continue to grow, albeit at a slower pace than initially expected. It is clear that the capacity of PKU clinics, particularly in the U.S., to treat adult PKU patients with Palynziq has not recovered the capacity lost due to the pandemic. As a result, we have initiated an active project to identify alternate prescribers in the United States where clinic capacity is at a deficit compared to adult patients who could benefit from Palynziq. We are targeting endocrinologists for this initiative, and our research indicates both an interest in treating PKU and the capacity to manage treatment with Palynziq. We are still in the early stages of this effort and have certified a number of new prescribers, and we will keep you informed as the impact of this initiative is felt on our business going forward. Continuing with the PKU franchise, Kuvan contributed $58 million in revenue in the second quarter of 2022, down slightly from the first quarter of this year. As we have stated previously, as Kuvan nears the end of its lifecycle since losing market exclusivity in the U.S. in October 2020, we are gratified to have retained meaningful market share and resulting revenues. However, based on current trends, we are lowering full year 2022 Kuvan revenues guidance to between $210 million and $235 million. Lastly, with the potential positive EMA decision for ROCTAVIAN expected in the near future, we are ready for launch. Our team is prepared and encouraged that our longer-term data results offer a compelling value proposition and treatment option for adults with severe hemophilia A, and we look forward to providing you with more detailed updates upon approval. In conclusion, in 2022, we anticipate increased demand for all of our commercial brands with the exception of Kuvan as described. Our NPS products are expected to contribute significantly to revenue growth this year. We also expect VOXZOGO to be a meaningful factor in this ramp as noted in today's increase in full year revenue guidance. We believe that robust prescription demand represents the foundation for continued growth, including in new markets throughout 2022. Thank you for your attention, and I will now turn the call over to Hank for an R&D update.

Hank Fuchs, President Worldwide Research and Development

Thanks, Jeff, and thank you all for joining us today. With the European decision for ROCTAVIAN now on the horizon following the positive CHMP recommendation, we are working diligently on the BLA for resubmission by the end of September. Our belief in the potential for ROCTAVIAN to be transformational for people with severe hemophilia A only strengthens with each passing year. As we announced in May and also included in an oral presentation at ISTH in July, durable hemostatic efficacy was maintained over six years in our ongoing Phase I/II study of ROCTAVIAN in the 6e13 cohort with a mean cumulative annualized bleeding rate of less than 1, substantially below baseline levels on standard of care. The safety profile from the study remains consistent with previously reported data with no delayed onset treatment-related adverse events. Needless to say, we've been very pleased with the ROCTAVIAN results across the Phase III and Phase I/II programs and look forward to a potential marketing authorization in Europe in the third quarter. Turning to VOXZOGO, in June, we were pleased to share favorable 52-week results from our global Phase II study in infants and young children with achondroplasia at the Endocrine Society's Annual Meeting. The improvement observed in score and annualized growth velocity observed was consistent with what was observed in children over five years of age. We plan to meet with U.S. health authorities in the second half of the year to discuss expanding access to younger children. Finally, turning to the early-stage pipeline, all of the candidates under development continue to advance with BioMarin 255, which targets a subset of chronic renal disease. We've received the go-ahead from the Food and Drug Administration to move forward with the multiple ascending dose portion of our Phase I/II study. Regarding BMN 331 for hereditary angioedema, we have dosed patients in the Phase III HARMONY study to evaluate this investigational AAV5-mediated gene therapy for patients with hereditary angioedema. Concerning BMN 351 for Duchenne muscular dystrophy, we expect to file an IND this winter. Our preclinical studies of BioMarin 349 continue to build our enthusiasm for its potential to dramatically improve liver health in people living with A1AT deficiency. For BMN 293, formerly referred to as Dana 001, we are on track to be the next gene therapy clinical candidate for treating hypertrophic cardiomyopathy caused by mutations in the protein C3 gene. Lastly, we continue to advance BMN 349 and 293 towards INDs in the second half of 2023. In the coming weeks, we look forward to the EC's decision for ROCTAVIAN to be followed by resubmission of the BLA in the United States. Thank you for your support, and I will now turn the call over to Brian to update financial results for the quarter.

Brian Mueller, Executive Vice President and Chief Financial Officer

Thank you, Hank. Please refer to today's press release summarizing our financial results for full details on the second quarter of 2022. Since Jeff touched on many of the topline results from the commercial business, I will primarily focus on operating expenses, bottom line results, and other key financial updates for this quarter. As usual, all results will be available in our upcoming Form 10-Q, which we are on track to file over the next couple of days. As we have been highlighting over the course of this year, we believe that 2022 is an exciting and transformational year for BioMarin. Resuming a cycle of substantial revenue growth and expectations to transition to sustainable GAAP profitability are aspirational milestones that we have been working toward for years. We are pleased to be tracking the plan based on the company's second quarter and first half results provided today. Total revenue growth of 13% in the second quarter of 2022 compared to the second quarter of 2021, excluding Kuvan, has put us on a path to achieve our 2022 GAAP and non-GAAP income goals. One comment on how our planned 2022 revenues are split between the first half and second half of the year is that while Naglazyme and Vimizim order timing were weighted to the first half of the year, as Jeff noted, second half revenues are expected to benefit from growing VOXZOGO and Palynziq revenues compared to the first half of the year, plus the potential for a modest amount of ROCTAVIAN revenue. As a result, total revenues in the second half of the year are expected to be roughly even with the first half of the year. The strong VOXZOGO launch and consideration of the trends observed across our other brands drove the increase to our full year 2022 total revenue guidance to between $2.06 billion and $2.16 billion. Additionally, regarding the impact of foreign currency exchange rate volatility on revenues, the strong U.S. dollar has affected many companies' foreign currency-denominated revenue in 2022. While BioMarin is not immune from the resulting decreases in mostly euro-based revenue, we are pleased to observe that our foreign currency hedging program is providing the intended protection. Based on current exchange rates, we project that the net impact on our full year 2022 revenues after hedging will be a relatively modest negative effect of approximately $15 million versus our original 2022 guidance expectations which does incorporate some of the exchange rate volatility observed earlier in the year. Moving to operating expenses for the second quarter of 2022, both R&D and SG&A expense fell in line with our expectations. R&D expenses for the second quarter were $158 million, a slight decrease compared to the second quarter of 2021, reflecting decreased VOXZOGO development efforts after the marketing approvals in the second half of last year, which was mostly offset by increased R&D on our early-stage programs. SG&A expenses for the second quarter of 2022 were approximately $197 million compared to $184 million in the same period last year, with the largest component of the increase being the VOXZOGO global commercial launch efforts and ROCTAVIAN commercial launch preparation costs. Moving to bottom line results for the second quarter and first half of 2022, just a reminder that during the first quarter of 2022, the company sold the priority review voucher received with the approval of VOXZOGO in the United States. While the gain on the sale of the PRV remains the largest single contributor to first half GAAP net income, we are pleased to report GAAP net income during the second quarter of 2022, totaling $28 million and $149 million for the first half of the year. Based on this strong first half 2022 performance, we have slightly improved our full year 2022 GAAP net income guidance range by $10 million to $105 million to $145 million. While we have improved the full year guidance, we recognize that the full year math in light of $149 million of first-half GAAP net income might reflect a net loss for part of the second half of the year. This is due to some of the aforementioned revenue timing and some possible larger expense items in the second half of the year, but we remain confident in our core business and generating GAAP net income for this year and beyond. Regarding non-GAAP income, Q2 2022 non-GAAP income of $109 million was slightly higher than the 2021 second quarter non-GAAP income of $98 million, and full year 2022 non-GAAP income guidance remains unchanged at between $350 million and $390 million. Turning to total cash and investment, we ended the second quarter of 2022 with $1.5 billion flat compared to year-end 2021. The company continues to incur quarterly timing differences in several cash flow categories, mainly working capital timing. However, the business did earn approximately $56 million of operating cash flow during the second quarter of 2022. In closing, the BioMarin team is pleased to use this midway point of 2022 to both acknowledge the strong business performance through the first half of the year and the promising expectations for the rest of 2022. We continue to believe that our strategy of substantially growing revenues that drive increasing profitability and positive operating cash flow, while also investing in developing an innovative pipeline, are the best financial levers to fuel growth further into this decade. Thank you for your attention, and we will now open up the call to your questions.

Operator, Operator

And our first question comes from Salveen Richter from Goldman Sachs.

Salveen Richter, Analyst

Two questions here. One is with regards to your outlook for ROCTAVIAN. Are you ready to launch here? And once you have revenue from this product, how are margins and profitability expected to be impacted longer term? And then the second question is just about drug pricing reforms. As you're looking at the proposed bill here, how will BioMarin be impacted in just orphan drugs in general? Just wondering if they get carved out to a good degree here.

Jeff Ajer, Executive Vice President and Chief Commercial Officer

Yes. Thank you, Salveen, for the question, particularly for the outlook for ROCTAVIAN launch in EMEA. We are super excited about that. We have a team in place that's most recently been busy successfully with the VOXZOGO launch. It is largely that team that will be tasked with the ROCTAVIAN launch. So we have a good track record there. I would say, there's reason to believe prospectively in ROCTAVIAN's success in Europe, if we receive positive approval from the EC. I would go back quickly to what we believe are the five criteria that should be met to set up a successful commercial gene therapy program, of which ROCTAVIAN satisfies all five criteria. These include: one, the disease presents a significant remaining unmet need, as we've described in hemophilia; two, a material treatment effect size which includes clinical effect, quality of life effect, and a convenience benefit; three would be a pharmacoeconomic benefit which ROCTAVIAN has clearly set us to deliver and as we've described previously; four would be a material population to treat. We believe that many gene therapies being developed target esoterically small patient populations with limited commercial potential; and five would be a prepared team on the ground that is experienced and ready to launch. So, as mentioned, ROCTAVIAN meets all of those criteria. That's the reason for our optimism.

Brian Mueller, Executive Vice President and Chief Financial Officer

Yes. Thanks, Salveen. This is Brian. I'll comment on margins. The ROCTAVIAN EU launch is expected to be a significant contributor to what was already planned margin improvement. Today, we're observing that the VOXZOGO launch is already contributing. When we look at our SG&A as a percentage of revenue today, it's about 40%. This reflects the global infrastructure we've built to support our seven approved products sold in over 70 countries. The VOXZOGO contribution alone is leveraging our commercial organization. While the ROCTAVIAN launch will require some incremental investment, it's mainly a leverage story from that commercial infrastructure mentioned by Jeff. Over time, as ROCTAVIAN revenues ramp, we expect the investments in operating expenses to be significantly less, which will contribute to the bottom line and margin improvement going forward.

Jeff Ajer, Executive Vice President and Chief Commercial Officer

Regarding drug pricing reform, if it progresses through legislation, we expect it will impact companies with large Medicare drugs, particularly companies that have a history of raising prices more than inflation rates in the U.S., particularly the Consumer Price Index (CPI). BioMarin, however, has very limited exposure to Medicare, and it is not our practice to raise prices ahead of CPI. Although we find it unfortunate to move forward in a general sense, we do not foresee a material impact on our business.

Operator, Operator

And our next question comes from Joseph Schwartz from SVB Securities.

Joseph Schwartz, Analyst

Congrats on the great quarter. I have a question on VOXZOGO and then ROCTAVIAN. So I was curious if you could discuss any lifecycle management strategies to fortify your achondroplasia franchise ahead of potential competition. Are you still working on long-acting formulations? Can you provide an update on that status? And are you taking steps to improve the administration device or procedure or generate more data to show the real-world value of VOXZOGO to ensure your brand has staying power if competition arises?

J.J. Bienaime, Chairman and CEO

Just a few words about lifecycle management; I'll let Hank answer the rest of your question. Yes, we have announced earlier that we have a pen device in late-stage development, which we hope could hit the market around 2024. This will make the administration of the drug easier. Actually, Greg Guyer is in charge of this device; perhaps he could say a few words about it, followed by Hank addressing your question on long-acting formulations and other lifecycle activities. So Greg, do you want to share your insights?

Greg Guyer, Executive Vice President and Chief Technical Officer

Yes, thanks, J.J. The pen device is well underway. We believe it will be a significant advancement in convenience for patients, and it will simplify administration. So that's well underway. We have some studies we need to conduct with the pen and obviously the approval process to complete. We hope that this will hit the market in the U.S. and Europe by 2024.

Hank Fuchs, President Worldwide Research and Development

I was going to add a few words regarding your questions about lifecycle planning. We have very robust plans immediately next, including interactions with the FDA around broadening the label in the U.S., which is more appropriately represented on a global basis. Japan recently approved the product unrestricted in regard to the younger living age. So that's a crucial step for fortifying the franchise. The pen is a key part of this, alongside the conversion to full approval based on final adult height. We also see emerging information about potential additional activity and indications beyond achondroplasia. Finally, our long-acting program is in place, and as we gain more experience in this population, we're considering even improved options for treatment. There is a lot of activity ongoing to bolster VOXZOGO's market presence and future potential.

Operator, Operator

And our next question comes from Geoff Meacham from Bank of America.

Geoff Meacham, Analyst

Congrats on the quarter. I had a couple of questions on ROCTAVIAN. The first one is, as you approach the European approval, what have you done or can you do to inform the cost-benefit analysis? Has there been any extra work done to engage with payers regarding pricing? I know, J.J., you mentioned shifting from an annualized model to a single payment. And the second question also on ROCTAVIAN is just, Hank, could you share any updates on the potential for retreatment using a different expression vector or viral effect?

J.J. Bienaime, Chairman and CEO

Thanks. I'll start and then I'll have Jeff and then Brian provide insights on the revenue recognition plan for ROCTAVIAN revenues, followed by Hank on your final question. Indeed, as compared to two to three years ago, we initially thought that payers, whether in Europe or the U.S., would be interested in staggered payments over time. However, they are not. Most of them work on an annual budget and find it difficult to commit to payment over a multi-year period. They're also very interested in outcome-based agreements, and Jeff and Brian can explain the mechanics of that. Additionally, based on the strong Phase II data showing durability of treatment effects for up to six years, we feel we're in a strong position to negotiate favorable agreements with low risk to payers, effectively mitigating their concerns regarding durability.

Jeff Ajer, Executive Vice President and Chief Commercial Officer

Yes. Thanks, J.J. With the outcome-based agreements, we are actively working with European payers, particularly in Germany, which will be our first launch market. As J.J. outlined, we are taking on the risks of nonresponse and durability over time in these agreements, addressing payer uncertainty. Based on clinical trial data, we assess the risk of nonresponse is very low. Most notably, our analyses throughout this process have indicated that ROCTAVIAN offers a superior treatment option compared to existing therapies, and we are tailoring economic assessments based on the needs of various health care systems before filing in major EU markets just after potential approval.

Brian Mueller, Executive Vice President and Chief Financial Officer

And to elaborate on the financial specifics regarding these outcome-based agreements, we anticipate upfront payments and revenue recognition as we deliver to customers. For these agreements, we will recognize financial exposure from these commitments to customers, although we believe the reserves required will be modest due to the strong response rates and durability we've observed. We expect these adjustments to fit within our historical approach to gross-to-net revenue considerations, so more insights will follow as we approach the launch.

Hank Fuchs, President Worldwide Research and Development

Regarding the potential for retreatment, we have numerous research programs aimed at understanding mechanisms of attrition of expression. We have the largest repository of liver biopsy data that continues to grow, which is helping us learn about factors leading to diminished RNA expression or complete vector loss. We will explore non-viral vector delivery methods, alternative serotypes, and other strategies to enhance and sustain gene therapy expression. Our goal is to provide meaningful options for patients who experience diminished efficiency, but we are still in exploratory phases.

Operator, Operator

Our next question comes from Phil Nadeau from Cowen and Company.

Phil Nadeau, Analyst

Two from my side, also one on ROCTAVIAN and one on VOXZOGO. On ROCTAVIAN, the press release mentioned a likely nine-month review for the refiling. Is the standard PDUFA six months? Could you clarify why you believe nine months is likely? Has this been communicated by the FDA, or is this your own assessment? How would this work? Would you get an initial six-month PDUFA, and then it might be extended when you submit the data, as mentioned in the press release?

Hank Fuchs, President Worldwide Research and Development

Yes, I understand the confusion. The likelihood of a nine-month review is mentioned as we are reiterating something said previously, regarding delays due to FDA requests for additional information during submission. We do not want to imply either a likely or unlikely situation regarding the review timeline. The agency may request more review time if they require more data and will inform us about any extensions to the PDUFA timeline. Currently, we do anticipate submitting at the end of September with a new six-month PDUFA, and we’re prepared for either scenario following approval.

Phil Nadeau, Analyst

That's very helpful. On VOXZOGO, the press release notes that there are 164 patients on commercial therapy in the U.S., which implies about 164 patients were added over the first six months of the year. Should we expect that pace to continue in the second half of the year? Were there any reasons for a bolus in that number? Or might it accelerate in the second half as expert centers get the referral networks up and running?

Jeff Ajer, Executive Vice President and Chief Commercial Officer

It's a great question, Phil. I would guide toward relative continuity of patient growth. It's likely that early patients came from expert clinic centers participating in clinical trials, and we might have seen a fast run from those sources. More recently, we've been seeing increased referrals from community-based pediatric endocrinologists, which we anticipated and are currently developing. Overall, I expect patient growth to continue steadily in the United States.

Operator, Operator

Our next question comes from Paul Matteis from Stifel.

Paul Matteis, Analyst

I wanted to ask a couple of things about ROCTAVIAN uptake in Europe. Could you frame for us how attitudes towards prophylaxis therapy and hemophilia A vary across European countries? How might that impact the target population for ROCTAVIAN? Also, when talking to clinicians, we observe variable feedback on the target population in their minds in terms of early adopters. How are you thinking about the first wave of patients most likely to receive this drug, and what proportion of the overall population does that demographic represent?

Jeff Ajer, Executive Vice President and Chief Commercial Officer

There is variability in Europe. We are focusing on major markets in Europe initially, namely the EU4: Germany, France, Italy, and Spain. I believe the primary impact on adoption in the first couple of years will be our ability to secure reimbursement across Europe. So, that geographic aspect is significant. I can say we anticipate targeting a sizable population of patients. Regarding early adopters, while we can't disclose precise numbers for competitive reasons, prescribers generally believe ROCTAVIAN will appeal to around 35% of eligible patients, and about 80% of clinicians indicated interest in prescribing it within the first year of approval.

J.J. Bienaime, Chairman and CEO

Let me just comment that while there are various perspectives from physicians on the percentage of their patients who will use gene therapy, it's crucial to consider the context of the questions being asked. For instance, if a doctor states they intend to treat 10% of their patients with gene therapy, they may be discussing all hemophilia A patients or just severe cases. Thus, there can be discrepancies depending on how questions are framed and the nature of the discussions.

Operator, Operator

Our next question comes from Gena Wang from Barclays.

Gena Wang, Analyst

Also, I have two questions. The first is on VOXZOGO. What is the practice environment like in Japan and Australia? Are patients concentrated in major centers? Additionally, are the prices for Japan and Australia around $250,000? The second question is regarding ROCTAVIAN. After your BLA resubmission, when might you know if you will have an Advisory Committee (AdCom)? Do you think the FDA’s decision on whether uniQure will have an AdCom for their hemophilia B program will have a direct read-through for you?

Jeff Ajer, Executive Vice President and Chief Commercial Officer

In Japan, it's significant because it is the only market that has approved growth hormone for treating achondroplasia. I've personally visited Japan and met with key pediatric endocrinologists specializing in the treatment of achondroplasia. They believe that while growth hormone is not effective, parents are still eager to pursue treatment options for their children, making this an environment favorable for VOXZOGO’s entry. The established treatment network is already in place, which makes our task easier. Regarding pricing, we believe that pricing will align well with the U.S. and Germany based on references available in the market. In Australia, it's a similar situation as the treatment community is equally engaged. Australia may experience longer reimbursement processes but has a strong market potential.

Hank Fuchs, President Worldwide Research and Development

Regarding the resubmission process, it’s a bit less clear. There isn’t a defined structure as in the case of original submissions. With a resubmission, we won’t receive specific milestone updates like the day 14 filing letter or the mid-cycle meeting, which makes it challenging to predict an Advisory Committee meeting. We'll learn of these requests only when the FDA informs us. The timing of uniQure's PDUFA date is also important. Their date is set for November so if an AdCom is needed, it will occur before our submission. Due to various factors, it’s tough to predict if there will be direct implications for us.

Operator, Operator

Our next question comes from Robyn Karnauskas from Truist Securities.

Unidentified Analyst, Analyst

This is Robyn. Hank, can you share your confidence regarding the U.S. filing for ROCTAVIAN and confirm if your September timeline is on track? Have you submitted any additional data since your last update? Also, have there been any further communications with the FDA that bolster your confidence in the timeline? Regarding VOXZOGO, the growth in the number of patients quarter-over-quarter was quite impressive. Did this align with your expectations? Lastly, although it may be early to discuss, do you have any initial compliance data points?

Hank Fuchs, President Worldwide Research and Development

We are confident that we will be submitting in the September timeframe. Our confidence arises from informal communications we've had with the FDA regarding specific points they want clarified and progress in completing the necessary work. Therefore, we feel reassured that our application will proceed smoothly.

J.J. Bienaime, Chairman and CEO

The VOXZOGO launch is performing better than we had anticipated. Regarding compliance, we have heard of only two to three patients discontinuing therapy to date worldwide. This is quite different from claims made by our competitors regarding their experiences. In essence, our compliance has been very strong, and we will continue to monitor these trends.

Jeff Ajer, Executive Vice President and Chief Commercial Officer

Yes, that’s correct. The launch has exceeded our expectations, and regarding compliance, we are primarily aware of figures in the U.S. As of now, we only have information indicating minimal discontinuations, particularly compared to experiences reported by some competitors. Our early indications point to strong durability of adherence among patients, which gives us confidence moving forward.

Operator, Operator

Our next question comes from Matthew Harrison from Morgan Stanley.

Matthew Harrison, Analyst

I have two quick questions. Firstly, on Palynziq, outside of the treatment center issues, is there anything else you can do to try and reaccelerate growth? Secondly, regarding Dynacor and that asset, what's happened? About two years ago, I believe you were close to filing an IND. Can you tell us what changes you've had to make in that program, and why you feel confident you'll be able to file an IND next year?

J.J. Bienaime, Chairman and CEO

I'll begin with Palynziq and then have Jeff continue with his insights, followed by an update on Dynacor. Generally, growth for Palynziq has been steady but it can take time with enzymes. We've learned from similar products that growth can surge after initial adoption, much like our expectations for Palynziq. We anticipate double-digit growth this year. There have been challenges with PKU centers prioritizing patients with severe disorders, but now we are redirecting focus to enable starting treatment beyond the hospital environment and increasing prescriber outreach.

Jeff Ajer, Executive Vice President and Chief Commercial Officer

Exactly. The adult PKU patient situation is unique because PKU clinics have historically operated within large academic institutions, which limits access. We are targeting adult endocrinologists, who are qualified to manage complex therapies, and our analysis suggests they have both the capacity and interest in treating PKU. We've launched initiatives to engage further and establish a stronger prescriber base. We also began offering a home program for new patients, allowing them to complete their first injection without visiting a PKU clinic, which will remove barriers to initiation.

J.J. Bienaime, Chairman and CEO

As for Dynacor, we remain optimistic regarding our IND filing timeline. Our team has made substantial advancements focusing on manufacturing processes and testing involving human cardiomyocytes. This progress positions us well for an IND submission next year, along with continued advancements with BMN 349 as part of our pipeline.

Operator, Operator

Our next question comes from Tim Lugo from William Blair.

Tim Lugo, Analyst

Congratulations on the strong launch. Could you provide an update on VOXZOGO for infants? I know you have the investigator study with 52-week data next year. You also have the Phase II patients at risk of surgery study ongoing. What is your regulatory strategy for these patients?

Hank Fuchs, President Worldwide Research and Development

We have several important initiatives regarding infants. Our 206 Phase II study's outcomes are trending positively and we believe that could lead to a label amendment. However, the FDA may have specific criteria that could delay approval processes. The current studies concerning risks for surgery have almost enrolled, and we anticipate reading the data shortly. We're also working on studies exploring VOXZOGO’s effect in children with non-standard achondroplasia mutations, which show early promising trends.

Unidentified Analyst, Analyst

This is Akash. I have a quick question on VOXZOGO. I know you already covered this, but regarding the Phase II data in the three indications presented at PEF earlier this year, can you comment on the development timeline? How will you further advance these indications? Is there potential for pursuing accelerated approval for these indications? When can we expect updates on that?

J.J. Bienaime, Chairman and CEO

I wanted to point out that Dr. Dauber's study is still ongoing, and we are in discussions with regulatory bodies regarding the design of trials for indications beyond achondroplasia. I cannot set a firm timeline at this moment, but as soon as we have further specifics, I'll ensure they are communicated. We are highly motivated to explore every possible option for VOXZOGO's innovative applications for patients with growth deficiencies.

Debjit Chattopadhyay, Analyst

On VOXZOGO, what's the net price in ex-U.S. territories right now? And for ROCTAVIAN, how should we think about the number of hub centers in Germany initially and the three major markets over the remainder of '23?

Hank Fuchs, President Worldwide Research and Development

Regarding pricing outside the U.S., we anticipate achieving a finalized price under benchmarking models once reimbursement discussions are concluded. Regarding ROCTAVIAN's hub model, we are looking at establishing low double-digit hub centers in both Germany and France. By tackling a smaller number initially, we can train effectively and gain experience treating patients before expanding further across Europe.

Operator, Operator

Our next question comes from an undisclosed source.

J.J. Bienaime, Chairman and CEO

Thank you, operator, and thank you all for joining us today. Our results in the first half of the year underscore the strength of our brands and our execution across the organization. As reported, the addition of VOXZOGO to our commercial portfolio is an important component of our growth story and paves the way for GAAP profitability this year and beyond. We look forward to the potential launch of our next significant opportunity with ROCTAVIAN in Europe later this year. Together with VOXZOGO, we believe both drugs will drive substantial value for our patients, employees, and shareholders over the next few years. Thank you for the opportunity and support; we look forward to seeing you soon.

Operator, Operator

This concludes today's conference call. Thank you for attending.