BioMarin Pharmaceutical Q2 2025 Earnings Call Transcript

Quartr
Provided by Quartr
August 4, 2025

Key Takeaways

  • Positive Sentiment: BioMarin delivered 16% revenue growth in Q2 with double‐digit year‐over‐year gains across all business units and raised its full‐year 2025 revenue guidance to $3.125 billion.
  • Positive Sentiment: The company expanded non-GAAP operating margin guidance to 33–34% and increased EPS guidance to $4.40–4.55, reflecting significant profitability expansion and strong operating cash flow growth (+55% to $185 million).
  • Positive Sentiment: BMN 333, a long-acting CNP candidate for achondroplasia, achieved >3× AUC vs. a competitor in healthy volunteers, enabling a registrational Phase 2/3 study to start in H1 2026 with a targeted approval in 2030.
  • Positive Sentiment: BioMarin completed the acquisition of Inozyme, adding BMN 401 for ENPP1 deficiency to its portfolio and expecting pivotal Energy 3 trial data in 2026.
  • Positive Sentiment: Commercial momentum continued with VOXZOGO up 20% to $221 million, enzyme therapies up 15%, and both PALYNZIQ and VIMIZIM posting >20% growth, underpinning confidence in global patient demand.
AI Generated. May Contain Errors.
Earnings Conference Call
BioMarin Pharmaceutical Q2 2025
00:00 / 00:00

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Operator

Good afternoon. My name is Audra, and I will be your conference operator today. At this time, I would like to welcome everyone to the BioMarin Pharmaceuticals Second Quarter twenty twenty five Conference Call. Today's conference is being recorded. All lines have been placed on mute to prevent any background noise.

Operator

After the speakers' remarks, there will be a question and answer session. At this time, I would like to turn the conference over to Tracy McCarty, Investor Relations at BioMarin. Please go ahead.

Traci McCarty
Traci McCarty
Group VP, IR at BioMarin Pharmaceutical

Thank you, operator. 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 those factors detailed in BioMarin's filings with the Securities and Exchange Commission, such as 10 Q, 10 ks, and eight k reports. In addition, we will use non GAAP financial measures as defined in Regulation G during the call today. These non GAAP measures should not be considered in isolation from, as substitutes for, or superior to financial measures prepared in accordance with U.

Traci McCarty
Traci McCarty
Group VP, IR at BioMarin Pharmaceutical

S. GAAP, and you can find the related reconciliations to U. S. GAAP in earnings release and earnings presentation, both of which are available in the Investor Relations section of our website. Please note that our commentary on today's call will focus on non GAAP financial measures unless otherwise indicated.

Traci McCarty
Traci McCarty
Group VP, IR at BioMarin Pharmaceutical

Introducing BioMarin management team today on the call, we have Alexander Hardy, President and Chief Executive Officer Brian Mueller, Executive Vice President, Chief Financial Officer Kristen Hubbard, Executive Vice President, Chief Commercial Officer and Greg Fryberg, Executive Vice President, Chief R and D Officer. I will now turn the call over to BioMarin's President and CEO, Alexander Hardy.

Alexander Hardy
Alexander Hardy
President & CEO at BioMarin Pharmaceutical

Thank you, Tracy, and thank you all for joining us today for BioMarin's second quarter update. Now moving to Slide six. We were very pleased with our Q2 performance across all aspects of the business, including strong growth, exciting progress across the pipeline and delivery of our business development strategy. Starting with our strong growth in the second quarter, leveraging our business unit structure to drive focus and accountability, BioMarin achieved double digit year over year revenue growth and significant profitability expansion. Turning to pipeline progress.

Alexander Hardy
Alexander Hardy
President & CEO at BioMarin Pharmaceutical

I'm excited to share that BMN three thirty three, BioMarin's long acting therapy for children with achondroplasia achieved our target profile. Our goal is for BMN-three thirty three to demonstrate superiority to Voxago and set a new standard for the treatment of achondroplasia. We plan to advance the program to the next stage of development and expect to begin a registrational Phase twothree study in the first half of next year. Greg will provide additional details in a few moments. Moving to our business development strategy, we successfully completed the acquisition of Inozyme on July 1, broadening our enzyme therapies portfolio.

Alexander Hardy
Alexander Hardy
President & CEO at BioMarin Pharmaceutical

We executed the transaction with precision and focus, moving from agreement to close in less than two months. A lead program, BMN four zero one, formerly known as INZ701 is a treatment for ENPP1 deficiency, a condition with high unmet need and no approved treatment options. And we look forward to the pivotal data readout from this program in the 2026. Greg will provide an update on some anticipated milestones with BMN four zero one. Moving to Slide seven, our outlook for the remainder of 2025.

Alexander Hardy
Alexander Hardy
President & CEO at BioMarin Pharmaceutical

Building on the strong momentum so far, we will continue to execute on our 2025 priorities with urgency to deliver value to our stakeholders. Looking ahead and building on the momentum, we expect continued strong growth throughout the remainder of 2025, leading us to increase our full year guidance for total revenues, non GAAP operating margin and earnings per share. We are progressing our pipeline as announced today with BMN three thirty three advancing, BMN four zero one pivotal data expected to read out next year and a number of other updates anticipated over the coming quarters. And building on the InnoZyme acquisition, we plan to continue to augment our portfolio with strategic business development transactions to diversify our growth strategy. In conclusion, with the first half of the year now complete, I'm pleased with our progress and remain enthusiastic about our potential to deliver for patients, employees and our shareholders through the remainder of 2025 and beyond.

Alexander Hardy
Alexander Hardy
President & CEO at BioMarin Pharmaceutical

Thank you for your attention. I will now turn the call over to Brian to provide our financial highlights for the quarter. Brian?

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

Thank you, Alexander. Please refer to today's press release for detailed second quarter twenty twenty five results, including reconciliations of GAAP to non GAAP financial measures. All 2025 results will be available in our upcoming Form 10 Q, which we expect to file in the coming days. Now moving to Slide nine and starting with revenue.

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

We were very pleased with our strong performance in the 2025. Total revenues grew 16% in the quarter and 15% in the 2025 compared to the same periods in 2024. These results were driven by the underlying strength in global demand and new patient starts across the portfolio. Looking ahead, BioMarin is positioned for continued growth in the second half of this year. Revenue highlights in the second quarter include VOXZOGO revenue increasing 20% year over year to $221,000,000 fueled primarily by the ongoing success of the product's global expansion.

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

Midway through the year, as I previously noted, we expect second half Boxoggo revenue to be higher than the first half. And further, we expect second half revenue to be weighted to Q4 due to both the impact of our strategic skeletal conditions business unit initiatives and order timing outside of The U. S. Therefore, with better line of sight into the dynamics in The U. S.

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

And outside of The U. S, for the remainder of the year, we are targeting full year Voxilgo revenue of between $900,000,000 and $935,000,000 Enzyme Therapies revenue rose 15% year over year to $555,000,000 reflective of both strong demand and order timing from regions across the globe. With Palynziq, we continue to see strong year over year growth with Q2 marking two consecutive quarters of 20% growth. Vimizim was also a strong contributor to second quarter growth, increasing 21% year over year. Rocadian revenue was $9,000,000 in the second quarter led by contributions from The United States and Italy.

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

All of these factors contributing to our strong Q2 revenues give us confidence to bring up the lower end of full year 2025 total revenue guidance to $3,125,000,000 with the midpoint of our guidance range representing double digit year over year growth. Now moving to Slide 10 and operating expenses in the 2025. Non GAAP R and D expense in the second quarter was lower compared to Q2 twenty twenty four, benefiting from focused R and D investment in prioritized assets following last year's strategic portfolio review. Non GAAP SG and A increased in Q2 year over year, mostly due to our investments in the company's enterprise resource planning system implementation and business unit strategic initiatives. As mentioned in our first quarter update, we expect both non GAAP R and D and SG and A expense to increase over the 2025 due to our historical spend patterns, incremental operating expenses related to the Inozyme acquisition and continued advancement of our clinical programs and commercial initiatives.

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

These investments include R and D expense for Voxago and new indications and BMN three thirty three as well as expansion of commercial initiatives in our skeletal conditions and enzyme therapies business units. Non GAAP operating margin expanded significantly in the second quarter as compared to Q2 twenty twenty four, driven by strong performance across the P and L, including underlying revenue growth and current operating expense trends. We anticipate that higher operating expenses in the 2025 to support our business unit initiatives will decrease second half operating margin as compared to the first half of the year. Further, as just outlined, with revenue being back weighted to Q4, together with the expense timing, we expect profitability to be lower in Q3 as compared to Q4. All in all, continued strong revenue performance and underlying cost discipline enables us to raise full year 2025 non GAAP operating margin guidance to between 3334%.

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

Now moving to Slide 11 to highlight BioMarin's increasing profitability and operating cash flow. The bottom line continues to outpace top line growth at an impressive rate. In the second quarter, non GAAP diluted earnings per share of $1.44 increased at more than three times the rate of revenue growth, reflecting the flow through of strong operating margin performance to the bottom line. Looking to the remainder of 2025 and as with operating margin, we do expect increasing business unit investments to result in lower earnings per share in the second half of the year as compared to the first half with a decrease concentrated to the third quarter due to timing. Reported by the strong first half performance, we are raising full year 2025 non GAAP earnings per share guidance to between $4.4 and $4.55 In addition, BioMarin's increasing profitability continues to generate significant operating cash flow, reaching $185,000,000 in Q2, a 55% increase versus the same period in 2024.

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

Increasing operating cash flow is expected to continue going forward in support of our innovation expansion opportunities and future growth. Now moving to Slide 12 and to summarize, we are pleased with our financial performance across the business in the second quarter. And today's full year 2025 guidance update reflect our expectation of continued strong growth and value creation for shareholders. Separately, with the Enazyme acquisition completed on July 1, we expect to account for the transaction as an asset purchase and record the impact of the acquired in process research and development or IPR and D expense in our financial results in the 2025. Today's guidance updates do not yet reflect the IPR and D, and we will update full year guidance when we report Q3 as the transaction is reported.

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

Thank you for your attention, and I will now turn the call over to Kristen for an update on commercial activities in the quarter. Kristen?

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

Thank you, Brian. Now moving to Slide 14. I'd like to acknowledge the contributions from across the global teams that led to the strong second quarter performance from BioMarin's portfolio of eight innovative therapies. Starting with VOXOGO, 20% year over year revenue growth in the second quarter across a combined 51 countries was supported by new patient starts as well as strong treatment adherence. We were pleased to see strong uptake in the zero to four year old cohort in The U.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

S. New initiatives in The U. S, including increasing the field force as well as investments in digital promotion to drive Voxelvo expansion are working. As a result, we doubled the number of leads generated year to date year over year, which translated to an increase in net new U. S.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

Patients. With these initiatives firmly in place, we expect U. S. Patient uptake over the remainder of the year to be strong, while noting that the revenue results from these initiatives will be realized over the coming quarters. Now outside The U.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

S, FOXOGO expansion came from deeper penetration into existing countries as well as good adherence from children on therapy with incremental contributions from newly added countries. In summary, we are pleased to expect Voxsogo full year 2025 revenue growth of 25% year over year at the midpoint. Now moving to slide 15 and turning to hypochondriplasia, the next indication we are studying for Voxsogo treatment. Hypochondriplasia is a rare skeletal condition characterized by impaired bone growth leading to disproportionate short stature along with a wide range of medical complications and functional challenges. The comorbidities are highly varied and can look like any combination of disproportionality, macrocephaly, ear, nose, throat, and musculoskeletal related issues. Because hypochondriplasia is a clinically and genetically heterogeneous condition, it may be diagnosed late or not at all. Unfortunately, there is significant unmet need as the condition has no approved treatments except for growth hormone in Japan. People with hypochondriplasia can face significant health burdens and reduced quality of life. To date, data from Doctor. Andrew Dauber's investigator sponsored study has provided encouraging proof of concept results with Doxogo in hypochondriplasia.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

Enrollment pace in BioMarin's pivotal study exceeded internal expectations, giving us a good indication of demand for the treatment of this condition. We are leveraging our established capabilities to raise awareness of the upcoming Phase III hypochondroplasia dataset, which we plan to share in the 2026 to support a potential launch in 2027. And at this stage, we are actively engaging with the medical community to advance education on disease awareness and management. Through strategic partnerships with health care professionals, including achondroplasia thought leaders, advocacy groups, academic institutions, we aim to improve early diagnosis in hypochondroplasia to shape future treatment decision making with Voxova. Now moving to Slide 16 and our Enzyme Therapies business unit.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

In the second quarter, combined products delivered 15% growth year over year. Palynziq's strength in the quarter was driven by greater numbers of patients titrating to their daily maintenance dose and strong adherence. Incremental new patient starts were encouraging in the quarter, and we look forward to them achieving their maintenance dosing over the coming quarters to realize the full benefits of Palynziq. And if approved, we look forward to the opportunity to make Palynziq available to adolescents in The U. S.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

And Europe based on its demonstrated ability to lower Phe into the normal range and allow for an unrestricted diet even in people with the most severe form of PKU. We believe these two attributes will be particularly transformational for those preparing to transition into adulthood. Imazim was also a strong performer during the quarter, growing 21% in year over year revenues and benefiting from ongoing patient demand globally as well as the timing of large orders in certain regions. Across enzyme therapies, we expect strong trends to continue through the 2025 despite potential quarter to quarter fluctuations due to order timing as we've observed historically. In summary, the team delivered another quarter of strong performance across the globe.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

Despite the significant macro challenges many companies in our sector are facing, the essential nature of our medicines, our strong patient support programs and BioMarin's global reach keep these important therapies available for the people who need them. I want to thank the team for their continued commitment and perseverance. I'll now turn the call over to Greg for an update on R and D progress in the quarter. Greg?

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Thank you, Kristen.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Now moving to Slide 18. We're very pleased to share the first clinical update on BMN three thirty three, BioMarin's long acting CNP candidate for the treatment of achondroplasia. Today, we announced that we have observed encouraging PK results from our healthy volunteer study where BMN three three three demonstrated free CNP levels more than three times greater than the AUC levels reported for another long acting CNP as described in the British Journal of Clinical Pharmacology from June 2022. This profile represents a potential best in class molecule with the opportunity to drive even greater improvements in growth parameters versus available therapies and, by extension, to further improve measures of health and wellness in children with achondroplasia. Our own preclinical data, along with publicly available dose response data for long acting CNP agents, suggest that additional growth should be achievable with greater CNP exposures.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

We believe that safely achieving these PK results with BMN three thirty three means we have the right agent in hand to immediately test this hypothesis. Based on these results, we're planning to initiate the dose finding arm of our Phase twothree registration enabling program in the 2026 with a targeted approval in 2030 should the data be supportive. The Phase one study continues as planned with ongoing monitoring of safety and pharmacokinetics at our sixth and final planned cohort. We anticipate sharing this full dataset publicly at a conference in the first half of next year. We are very encouraged by these results thus far, and we'll continue to look for opportunities to accelerate the program.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

On slide 19, moving to our next regulatory filing, we're on track to submit applications to support an age extension for Palynziq to include adolescents with The U. S. And EU applications planned for the second half of this year. Recall that our Palynziq adolescent study, similar to our previous adult study, required participants to have sustained Phe levels greater than 600 micromole per liter despite available dietary and pharmacologic treatment. This is a more severe population than those in which the BH four analogs have been routinely used.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Beyond simple phe lowering, the promise of Palynziq is that it may offer adolescents the potential to consume more native protein during their formative years and to decrease or eliminate the need for medical food. We plan to share the complete data from our adolescent study at a scientific congress in the second half of this year, and we look forward to the possibility of expanding the Palynziq label into adolescents with potential approvals in 2026. On Slide 20, now turning to another Phase III asset, we're very pleased that the Enazyme acquisition was closed so rapidly, allowing us to carry forward BMN four zero one for the treatment of ENPP1 deficiency. ENPP1 deficiency is a rare, serious, and progressive genetic condition that can affect blood vessels, soft tissues, and bones in infants, in children, and in adults. BMN four zero one has the potential to be the first genetically targeted medicine for ENPP1 deficiency.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

We look forward to sharing a first look at the pivotal data from the ENERGY three study in one to 12 year olds in the 2026 and to progressing clinical development in other age groups once we finalize the integration and determine the most efficient paths forward. In addition to this initial focus on ENPP1 deficiency, we are already evaluating other potential indications with BMN four zero one, and we will share more details as they become available. Finally, on Slide 21, here is a snapshot of a few highlights expected across our pipeline through the next six quarters. Following today's healthy volunteer PK update for BMN three thirty three, we look forward to the start of our Phase twothree study in the first half of next year. Also in the 2026, we'll be sharing pivotal Voxsogo data and hypochondroplasia with submissions planned in the 2026 to support a potential approval and launch in 2027.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

We plan to submit our Palynziq adolescent data before the year's end in support of potential launches in The U. S. And Europe in 2026. BMN four zero one, as already mentioned, is expected to read out the ENERGY three study in the 2026 in one to twelve year olds, followed by a potential regulatory submission in that age group in the second half of next year with the goal of launching in 2027. With BMN three fifty one for the treatment of Duchenne's muscular dystrophy, our study is progressing as planned.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

In addition to previously discussed six and nine milligram per kilogram cohorts, which have fully enrolled, the study data monitoring committee recently approved escalation to a third preplanned cohort of twelve milligrams per kilogram, which should complete enrollment by the end of the year. We remain on track to share a more detailed clinical update by the end of this year. BMN three forty nine for alpha-one antitrypsin deficiency is also progressing in the clinic, and we're planning a Phase II study start in the 2026. In summary, we have a number of exciting readouts and regulatory filings on the horizon, and we look forward to sharing updates as they progress over the coming months. I want to thank you for your attention today.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

We will now open the call to your questions. Operator?

Operator

We'll take our first question from Paul Matteis at Stifel.

Paul Matteis
Paul Matteis
Managing Director, Head of Therapeutics Research at Stifel Financial Corp

Great. Thanks so much and congratulations on the quarter. I had a couple of questions on BMN three thirty three. I just wanted to clarify that the computing program you're referring to is Trans Con CNP as it relates to comparison to AUC data. And then as it relates to the data itself, can you just confirm the safety profile that you're targeting and whether or not increased exposure is running into any increased risk of hypotension or other side effects? Thanks so much.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

So, Paul, I, this is Greg Freiberg. I can confirm that the agent you're referring to is in that reference that we commented there. With regard to the profile we're seeing with three thirty three from a safety standpoint, absolutely nothing unexpected, though we have to remember this is a healthy volunteer study. It's in adults, not in children. That being said, nothing unexpected.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

And, again, we we also look at the genetic data in this disease where, you know, from the standpoint of, of patients who either have inborn, you know, mutations that cause them to have high CNP levels or activated receptors, nature has shown us that those patients, the only problems that they tend to have in their lifetime is that, number one, they're quite tall and there are skeletal complications of being over seven feet tall. But reassuringly, those patients don't have challenges in other organ systems. So again, we're hopeful that that read through will again be recapitulated when we pharmacologically go to higher levels of CNP.

Paul Matteis
Paul Matteis
Managing Director, Head of Therapeutics Research at Stifel Financial Corp

Great. Thank you.

Operator

We'll go next to Corey Kasimov at Evercore.

Cory Kasimov
Senior Managing Director at Evercore

Execution in the preliminary March data. On the achondroplasia front, I'd be interested in your thoughts on the evolving competitive landscape here with the recent data showing long acting CMP in combination with growth hormone and how you think that could impact the market down the road? Thank you.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Thanks, Corey. This is Greg Freiberg again.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

I'll take a stab at that. When the early data the growth hormone combinations card turned over, it was not surprising to see that there was added growth at a very early time point when growth hormone was added to CNP. Being able to achieve small, or or at least short term increases has never been the problem with growth hormone. On the contrary, it's been whether or not those, you know, those accelerations of growth can persist over time. Of course, achondroplasia is a condition which is not growth hormone deficient.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

And long term follow-up of these patients, particularly, you know, even the Japanese patients where it's approved in Japan, have only shown a couple of centimeters in increase in final adult height. Similarly, the kind of evidence beyond growth that we're seeing with CNP affecting facial morphology, looking at tibial bowing, all of these evidence of improving the patient's well-being and health, those haven't been as profoundly documented with growth hormone. So I you know, the the question with the growth hormone combination, there are a few of them. One would be, is this, something that's achievable over time? Secondarily, do we see mechanisms that accelerate bone age?

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Do we see those? You you won't see those in the first six months. So we'll we'll wanna you know, as a I think as a field, we'll want to see additional data before, the story is written as to whether that combination will add, anything significant for patients with achondroplasia.

Cory Kasimov
Senior Managing Director at Evercore

That's helpful. Thank you, Greg.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Welcome.

Operator

And next we'll move to Salveen Richter at Goldman Sachs.

Tommie Reerink
Tommie Reerink
Biotech Equity Research Associate at Goldman Sachs

Thanks for taking our question. This is Tommy on for Salveen. Just on the VOXOVA guidance, which was slightly adjusted. Could you lay out the contributions of the various factors as you think about ex U.

Tommie Reerink
Tommie Reerink
Biotech Equity Research Associate at Goldman Sachs

S. Order timing, demand and your U. S. Expansion initiatives? Thank you.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

Yes. Thank you so much for the question, Tommy. So as we had mentioned, we are expecting higher revenues in the second half relative to the first half of the quarter. And really, when we think about it throughout the quarter, this is primarily due to some of the shifting of large OUS orders that we see that we expected later in the quarter that will shift out a little bit, some into the 2026 as well, which will therefore kind of bring down the number a little bit. Not to mention, we are coming closer with only five to go in the year, and we just have a much better sense of kind of what we're trending toward and what we can forecast throughout the year.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

So what we did, as you see, is we brought down the top end of the range from nine fifty to nine thirty five, but I want to emphasize that that still represents 25% year over year growth.

Tommie Reerink
Tommie Reerink
Biotech Equity Research Associate at Goldman Sachs

Thank you.

Operator

We'll go next to Jessica Fye at JPMorgan.

Adam Ferrari
Adam Ferrari
Biotech Equity Research Associate at J.P. Morgan

This is Adam on for Jess. Thank you for taking our question. I just wanted to ask, can you walk us through when we should expect the next updates from the ITC proceedings? Thank you.

Alexander Hardy
Alexander Hardy
President & CEO at BioMarin Pharmaceutical

Yes. Thanks very much for the question. With regard to the ITC update, we're expecting that, has been publicly communicated, that we're we're gonna see the initial determination on, the June, actually, 06/08/2026, then a completion date, a target date for the completion of the investigation of ITC of 10/08/2026. So, those are the, those are the time frames that are being publicly communicated. There is a possibility of a summary determination for that time, but these are very much what has been communicated by the ITC at this point.

Operator

We'll go next to Akash Tewari at Jefferies.

Akash Tewari
Akash Tewari
Global Head - Biopharmaceutical Research at Jefferies

Hey, thanks so much. Can you just give us a little more detail about the design of that three thirty three superiority trial? Because when I look at the VOXZOVA Phase three, you had about 55 patients per arm. You're 90% powered to get a 1.75 average growth velocity delta. I feel like if you have the same powering per arm and you're going for superiority, you're probably looking at like a point eight to one centimeter improvement between March and VOXZOGO for that trial to hit on superiority.

Akash Tewari
Akash Tewari
Global Head - Biopharmaceutical Research at Jefferies

Is that the right way to think about efficacy? And like what gives you the confidence you can do that? And then maybe number two, can you talk about the potential to pursue maybe beyond weekly dosing with the profile that you showed in healthy volunteers? Thank you.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Thanks, Akash. Just dissecting your questions, one by one. From the standpoint of the Phase III study, we're not going to go into details on powering today, but we do have confidence that this is biologically a very reasonable hypothesis to test. Of course, we have the preclinical data in the mice where, again, in terms of attributable growth, we were able to almost double the amount of, skeletal growth that we saw in those models using the kind of doses with three thirty three that we've now been able to show, at least in a single dose study, are safe, in humans. Similarly, we've mentioned the human genetic data on the safety side.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

We also know that those individuals born with activating mutations in the pathway, they grow quite substantially, almost to seven feet tall or farther. But finally, if we look at the, the available data that's published for another long acting CNP agent, you know, marching upwards to the highest dose, there is proportionally an increasing amount of growth at each step along the way. By being able to then, in our minds, continue that curve upwards with increased exposure, we feel we confidently have the right molecule to test that hypothesis with three three three. I'll just add that, you know, we have we mentioned we're in our sixth cohort, right now. We've completed five, and two of them have met our criteria.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

So, again, we feel like we have, on the PK side, quite a bit of headroom and and feeling, very, very good about the results that we've seen. With, regard to the amount of attributable growth that we're going to look for in the comparative effectiveness study. What I would add is that we certainly have talked to patients. We've talked to physicians. We've talked to their caregivers.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

And, again, we've come up with an amount that we think, again, would be, meaningfully differentiated in the marketplace. And I would be remiss if I didn't add that this while this is a story where we talk about growth and talk about the number of centimeters, we also want to pull through to, of course, the markers of health and wellness. Spinal stenosis, of course, is something that we're we're following very closely. The the additional skeletal, facial, morphometry studies, all of those, we would be measuring, and we would hope to see meaningful improvements in the quality of life of these patients, these individuals who have this condition. So, you know, with that regard, we'll be sharing more information, over time on the study design.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

I'll just simply add that, you know, from, as you can extrapolate from some of the AUC comments I made, we would have the opportunity, if, if desired, to consider less frequent intervals than weekly. The question becomes which parameter do you want to prioritize? And for us, efficacy, increasing the ability, to drive health and wellness in the patients is what we're prioritizing at this point.

Operator

We'll take our next question from Joseph Schwartz with Leerink Partners.

Analyst

Andrea Park dialing in for Joe. Thank you for taking our questions. I know you're working on VMN three thirty three with the goal to launch in 02/1930. But in the meantime, how predictive is your load discontinuation rates for Voxago in an environment where there is no competition? How do you think about the discontinuation rates when there are other options, including once weekly or once daily Oracle prior to the availability of CMN three thirty three?

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

Yeah. Thank you so much for the question. This is Kristen Hubbard from Commercial. And just to speak to the adherence rates that we know today, we continue to see that the vast majority of children that are on therapy really do adhere to their daily dosing, and this is true across the globe. And we are really expecting that many of the new initiatives that we've started will continue to ensure this high compliance going forward.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

Now I will say that this is something that we've invested in, in terms of patient support programming. We think it is incredibly important that patients do adhere to their therapy, and so we've definitely put some support programming in place that will aim at driving adherence and really ensuring that we have an improved experience, in particular in some of those more high risk populations where we're truly seeing strong results in terms of adherence. And I do think that this is something that is one of BioMarin's core strengths at large across our portfolio. It's truly about finding patients through diagnostic efforts. It's about starting patients on treatment.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

And then importantly, it is really important that we keep patients on therapy because we know this is the most important thing for long term outcomes. That's what we're investing in and continue to do so.

Operator

We'll go next to Sean Lemaugh at Morgan Stanley.

Sean Laaman
Sean Laaman
Executive Director at Morgan Stanley

Afternoon, everyone, and thank you for taking my question. I hope everyone's well. Just thinking a little forward to your $4,000,000,000 revenue aspirations in 2027, I think it is. Just wondering how important other indications for Voxago to that and what sort of contribution do you think they might make? And even going beyond hypochondriplasia, indications such as Newnan and Turner, when might we expect those?

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

Sean, this is Brian Mueller. Thanks for the question. I'll take that one. So first, some remarks on the $4,000,000,000 revenue target in 2027. Given the many developments since we unveiled our new corporate strategy and 2027 guidance of $4,000,000,000 last year.

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

We are taking a full account of the latest information and plan to provide an update on our 2027 revenue guidance and our long term targets by the end of this year. So stay tuned on that. We will revert, shortly. I would answer the other part of your question that in the previous guidance, hypochondroplasia was the only indication expansion for Voxelgo that was launching in that 2027 window. So there's a modest contribution from hypochondroplasia in that original number. Thank you.

Operator

We'll take our next question from Gena Wang at Barclays.

Gena Wang
Gena Wang
MD - Biotech Equity Research at Barclays

Thank you for taking my questions. I also will ask about the three thirty three program. So Greg, you said that now you already dosed the six cohorts. What are the thoughts when you go into the patient population? Is the aim is to maintain area under curve over three times, any upper limit you will be looking for regarding the safety?

Gena Wang
Gena Wang
MD - Biotech Equity Research at Barclays

And then the if you can remind us the VOX00VO low dose, high dose, what was the area under curve comparison? We do understand the Cmax could be very different, but when you look at the area under curve, what was the difference between the low dose and the high dose for Voxelgo?

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Thanks, Gina. And let me take those, in order. With regard to the, data we have in hand for March, we feel that it's going to give us, you know, a totality of evidence that will allow us to pick, relatively speaking, a low, medium, and a high dose. At least, several of those will be, you know, again, at this three x or above is what we're anticipating, though picking those final doses will require us to finish the study and do the formal pharmacokinetic analysis. As we mentioned, this sixth cohort, recruited, hasn't completed, you know, in terms of its data collection.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

So that is ongoing. With regard to the original VOXOGO studies, the AUCs, because the half life was thirty thirty minutes to sixty minutes, as you note, the the calculations of AUC in terms of precision, we don't have a whole lot of confidence that comparing the 15 to the 30, for example, is going to give us all that meaningful data. But those numbers were much lower than the AUCs that we're seeing with the long acting, which has a half life on the order of days instead of a half life on the hour of minutes, you know, in in the thirty to sixty minutes. Beyond that, I can't give you any more details in terms of the numerics. But if you have any specific questions afterwards, we'll be happy to follow-up with you offline.

Operator

We'll move next to Ellie Merle at UBS.

Jasmine Fels
Jasmine Fels
Associate Analyst at UBS Group

Hey. This is Jasmine on for Ellie. Thanks so much for taking our question. Just another one on three thirty three, trying to understand what the three times greater AUC perceiving means. From your preclinical work, can you give any more color on what this level of CNP exposure translates to in terms of growth?

Jasmine Fels
Jasmine Fels
Associate Analyst at UBS Group

And then secondly, given this data that you've now seen, how does this impact your thinking on prioritizing three twenty three versus VoxoGo for other growth disorders going forward? Thanks.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Thanks for the question. With regard to the 3x growth, at least from a numeric standpoint, the preclinical model is probably the best, because, again, there's a case where, actually, we were able to recapitulate this sort of, you know, increase in exposure. So the control animals had, you know, were treated with a very healthy dose of Voxogo, and, again, all of the growth that that could, could deliver followed by, increasing titrating doses of three thirty three. And what we saw was at, roughly what we you know, what we're projecting are a three x margin compared to, again, what's been published for other long acting programs that we were able to unlock additional growth. And so the three x, again, is what we believe is a meaningful difference, in exposure compared to what was seen before.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

And in the animal models, again, we know that there's additional growth there. The question is going to be just how much is there. What we know for sure is that we have what we believe to be the right agent in hand to test that hypothesis. We believe that we're gonna be able to test multiple doses at that threshold or higher in the dose ranging phase two and that, before certainly the initiation of the comparative effectiveness study, we're gonna have a good handle on how much growth is there to be had. That being said, it is an unanswered question.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

The preclinical, the genetic, and the data from other long acting CNPs can only get us so far. And so having the right agent to test is the next step, and we're thrilled to be moving forward. We're, you know, excited about three three three beyond just achondroplasia. We're putting together our hypochondroplasia plan as we speak. All of the additional indications do require us to do a dose ranging study.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

So doing that as quickly as possible is the key to unlock that. And, again, having that arrow in our quiver is also going to allow us to think about additional indications where we might want a best in class c n long acting CNP agent. And, again, that's what we're hopeful that we have in BMN333.

Operator

We'll take our next question from Olivia Breyer at Cantor.

Olivia Brayer
Director & Senior Biotech Analyst at Cantor Fitzgerald

Hey. Good afternoon, guys. Thank you for the question. Can you give us an update on where you are with the citizen position? Have you had any back and forth dialogue with the agency?

Olivia Brayer
Director & Senior Biotech Analyst at Cantor Fitzgerald

And maybe just any comments on how confident you are that there will be action taken by the FDA here? And then just wanted to follow-up on some of the comments made around the long term guidance metrics. Is there something in particular that you're waiting to hear about before having better visibility into what those numbers could look like? Thank you.

Alexander Hardy
Alexander Hardy
President & CEO at BioMarin Pharmaceutical

Thanks very much for the questions. I'll take the first one. This is Alexander. So with regard to the systems petition, we've submitted that to the FDA. The FDA considers that during the review process for the competing molecule, with regard to determining the validity of our orphan drug prevention.

Alexander Hardy
Alexander Hardy
President & CEO at BioMarin Pharmaceutical

So, we do not expect to hear anything from the FDA until DUFA. As you know, that is November 30. So that's all the information we have to share right now on the situation with regard to the citizen competition. Now I'll hand it over to Brian to handle the second part of your question.

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

Yes. Thanks, Olivia. Following up on the the $4,000,000,000 in 2027, there's not a specific event that we're waiting to pass before we we give that updated view. It it really is just working through our collective refreshed view across everything that's changed over the last year. You know, there's, puts and takes.

Brian Mueller
Brian Mueller
EVP & CFO at BioMarin Pharmaceutical

We're we're considering recent trends in market research across our portfolio. We completed the Enazyme acquisition this quarter. And, of course, the BoxOGO IP litigation is still ongoing. So we're working through that. And once we do, we'll share the perspective.

Operator

Next, we'll move to Costas Bilores at BMO Capital Markets.

Kostas Biliouris
Kostas Biliouris
Director - Biotech Equity Analyst at BMO Capital Markets

Thanks for taking our question and congrats on the progress. Maybe some more color on some comments you made earlier. On the 3x difference between AUC, can you please clarify how exactly you performed the comparison? Was it 3x at least 3x across all doses you compared or only in the highest dose or only in some doses? And the follow-up is on Cmax.

Kostas Biliouris
Kostas Biliouris
Director - Biotech Equity Analyst at BMO Capital Markets

Does Cmax matter at all here maybe for safety or efficacy? And how does your Cmax compare with TransCon CNP? Thank you.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Thanks for the question. With regard to the ongoing study, just to repeat something I said, but I might have gone through too quickly. We've completed and analyzed five escalation cohorts. It's a healthy volunteer single dose study, and two of those cohorts already have met our AUC criteria of being greater than three x. That is greater than three x the AUC of which is published in and we put the reference in our slides for the other long acting CNP agent that's been discussed.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

From that standpoint, again, we have a sixth cohort that's running right now. All of these have been avoiding the kind of Cmax ranges where with Voxogo, we knew that we started to see a very predictable, effect on the vasculature, which was a drop in blood pressure and, some tachycardia in patients. That is a Cmax that is well understood from the preclinical models and from our own experience, and we're still, you know, almost tenfold away from that with regard to what we're seeing. Nothing is for free. And, of course, as your AUC goes up, so does your Cmax.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

And so from that standpoint, the Cmax, we predict, will be, greater than the other long acting CNP out there. The question is, is that problematic? And so far, it has not been problematic. We're moving forward. And, again, this is why we will, in patients, do a dose ranging of a high, medium, and low.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

That's a relative term, but a high, medium, and low dose of BMN three thirty three moving forward in order to test not only what kind of growth and effects on health and wellness that we can see, but also to make sure that that is safe in those patients.

Operator

We'll take our next question from Jason Gerberry at Bank of America.

Jason Gerberry
Jason Gerberry
MD & Equity Research Analyst - Biotech & Pharma at Bank of America Merrill Lynch

Hey, guys. Thanks for taking my question. One, just follow-up on the HCH opportunity and the commentary about getting to the patient earlier. I guess we observed with ACH or achondroplasia that getting the below five indication was really key commercially in number of geographies. And with HCH, at least in the prior phase two work, I think the average age was about six years of age.

Jason Gerberry
Jason Gerberry
MD & Equity Research Analyst - Biotech & Pharma at Bank of America Merrill Lynch

Your enrollment criteria is three years. So I just I I wonder, given it's it's a milder disease, the motivation to treat and and sort of the risk, I guess, a patient perspective that they're going to come on later in life and may not get the sort of lifetime benefit that they see in HTH. So just wondering if you can maybe expound upon, some of those efforts and how you see that evolving. Thanks.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

So I'll start thank you very much for the question, Jason. And so I'll start a little bit about the opportunity because you're absolutely right that these patients do tend to get diagnosed, later. It doesn't mean that there isn't a large unmet need in these patients. And I've mentioned a little bit on the prepared remarks and that is that you have comorbidities that we see, disproportionality being a big one, macrocephaly, ENT issues and musculoskeletal issues, excuse me. And what we know is that as we see in achondroplasia, the earlier that you can treat patients, the better.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

And so we are very focused on leveraging much of our relationships, our infrastructure to ensure that we are educating on the unmet need that is here in hypochondroplasia and importantly that we can encourage diagnosis as soon as possible. Given that this is both clinically and genetically a heterogeneous condition, it's important that we educate on the importance of diagnosis. That's precisely what we are focused on now as we await the phase three data.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Yeah. And I would just add that, you know, the study is for ages three to 18. So again, given the current state of diagnosis, we believe again that will serve a good number of patients. There is an infant study, that's ongoing as well that will, need to, you know, continue to enroll, and that will be delivering its data at a a later time point. But the bigger question that you bring up is, again, making sure that we do our part to not only measure but also report to the world the the health care burdens that these patients and their families are experiencing.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

And we began that process. We published some abstracts, continuing to do work, again, health care utilization, resources required by countries in order to care for these folks, but that will be an important part of the process here to continue to, again, create, not only, a dataset and the label, but also an urgency to treat based on what these patients are experiencing in the real world.

Operator

We'll go next to Alex Hammond at Wolfe Research.

Alexandria Hammond
Director - Head of Therapeutics at Wolfe Research LLC

Thanks for taking my question. Just a few on Voxsogo. So BioMarin has mentioned investing more in clinical coordinators to reduce the time needed to see a specialist. What's the average time from prescription that we're seeing currently, and where do you aspire to be? Then on increasing prescriber referrals from pediatricians to endocrinologists, how is that strategy progressing?

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

Yeah, thank you very much for the question. And I can say that what we are focused on is certainly reducing the time it takes from diagnosis to get patients on treatment, which can take on the order of months to do. I do want to give a little bit of color in terms of where we're seeing the growth right now, which I think is really important. And where we saw strong uptake that continued into the second quarter. And what we saw is that was this was especially in our youngest patients.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

So our biggest cohort that grew in the in quarter over quarter was zero to two year olds. And this is really important because this is expected to be the only approved treatment in this age group, but we also saw strong growth in the two to four year olds. And I think that this is really important because we're out there really trying to emphasize the importance, and this is true when we saw the consensus guidelines as well, in terms of early treatment so that we can ensure the maximum benefit of the therapy. Now in terms of how we are driving, you know, as as you've mentioned referrals from pediatricians into treaters, whether those be pediatric endocrinologists primarily, but also geneticists, that has been a successful strategy so far. We are seeing many of those new initiatives that are really taking place and taking off, and that was in part where we saw the growth being driven in the second quarter.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

So we expect that to continue over the quarters to come. And what we saw is when we look at the treater base in terms of where we're seeing growth in treaters, it's actually happening across all treater types. So we're seeing growth in geneticists, in endocrinologists and in pediatricians. So we're very happy with the results so far and anticipate continued investment in these areas.

Operator

Our next question comes from Ellen Horst at TD Cowen.

Ellen Horste
Ellen Horste
Equity Research Associate at Cowen

Thanks for taking my question, and congrats on the exciting quarter. Regarding BMN four zero one, I'm wondering what success looks like for the ENERGY three trial, including potential functional endpoints that might be required for approval outside The US. And then if you can remind us how many patients have been identified so far and what's involved with identifying the two thousand to twenty five hundred prevalence you estimate in your territory? Thanks.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

If I, this is Greg Forever. Just taking, that first question first. With the 401 card that's turning over, for those who aren't as familiar, this is the energy three study. So this is in the children, and and, you know, as opposed to infants or adolescents and adults. We'll be turning the card over in the first half of next year.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

And the success has two categories here. Those have been immortalized as co primary endpoints in Europe, as you noted. And those are not only normalizing the pyrophosphate levels, which is a sign again of biochemical normalization, but also functional endpoints. And in this case, it's the radiologic index that's noted, that, again, is looking at at the quality of bone in these children that still have their growth plates open. We have clear agreements with the Europeans as to what those functionality endpoints mean, and we're continuing to work, with the the FDA and other regulators, to to work through, again, the details of those.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

But it is a combination of both pyrophosphate as well as functional endpoints, as you point out. And we'll be measuring pain and some others in the protocol as well. But that's what's been agreed upon with the European regulators. To answer the second question, I think I'll, with regard to number of patients, I'm going to hand it off to Kristen.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

Thanks so much, Greg. So as you referred to, you're absolutely right in that in terms of the overall target patient population, addressable patient population, we do estimate that the range will be on the order of two thousand to 2,500 patients. I want to be very clear that the literature on this is very disparate, there's very high ranges. This is our current estimate in terms of what we believe the prevalence to be as well as our ability to ensure that we get diagnosis of these patients. Now, Unizyme had already identified over six hundred patients and we are carrying on much of the work that they were doing as we've taken this on.

Cristin Hubbard
Cristin Hubbard
EVP & Chief Commercial Officer at BioMarin Pharmaceutical

They have had great work and great success in building KOL networks that have been highly successful in finding these patients, but we believe that we can expand on that. Again, going back to it being a core strength of ours, and that is investing in diagnostic efforts to ensure that we're diagnosing and finding these patients. It's also really useful that this will slot right into our enzyme therapy business unit where it's highly complementary to the to the relationships and the established networks that we have today. So the specialties that we know treat in p p one deficiency, are are certainly include, but are not limited to the treaters that we already call on and that would be geneticists and endocrinologists. We're very much leveraging our infrastructure and networks therein to ensure that we can properly find these patients and then hopefully should the data turn out to be positive get these patients on therapy as soon as possible.

Allison Bratzel
Allison Bratzel
Senior Research Analyst at Piper Sandler Companies

We'll go next to Allison Bratzel at Piper Sandler. Hey, good afternoon and thanks for taking the question. Another one on BMN 333, just a clarification and sorry if I missed it, but can you help us better understand what exactly is gating to initiation of the dose ranging portion of the registration trial? And I think you've received FDA alignment for the Phase twothree plans, but could you just talk to your confidence in achieving regulatory alignment ex US and timing there? Thank you.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

Thanks for the question. And I'm very excited to share that we have regulatory alignment, you know, with multiple players around the globe at this point. And so the gating factor is, of course, completion of the current phase one study. It's very typical for healthy volunteer studies actually to study doses sometimes that are higher than what you'd study, again, giving you some PK buffer in phase two. And in that regard, having that complete dataset is a requirement before we move forward.

Gregory Friberg
Gregory Friberg
EVP, Chief Research & Development Officer at BioMarin Pharmaceutical

I'll also add, though, that we are moving very quickly. We're in the midst of protocol, you know, not only writing, but we're very far along in that process. And really, the next steps will be to initiate the study in the first half of next year. So if there is a gating factor, it's completion of the sixth cohort of the PK profile, but that is more of a formality in order to be able to, again, convince regulators and patients that, again, we have the data set in hand to justify moving forward in all of the doses that we've proposed. So more to come, but in that regard, we're thrilled to be able to be moving to this next step for the dose ranging of three thirty three.

Operator

And that concludes the Q and A portion of today's call. I will now turn it back to BioMarin's President and CEO, Alexander Hardy.

Alexander Hardy
Alexander Hardy
President & CEO at BioMarin Pharmaceutical

Thank you, operator, and thank you all again for joining us today. We're proud of the strong execution in the first half of this year, energized by the opportunities ahead, Continued momentum across our commercial pipeline, business development efforts, we believe BioMarin is well positioned to deliver significant value creation, patients, employees and our shareholders through the remainder of 2025 and beyond. We look forward to updating you on our progress in the quarters to come. Thank you very much.

Operator

And this concludes today's conference call. Thank you for your participation. You may now disconnect.

Executives
    • Traci McCarty
      Traci McCarty
      Group VP, IR
    • Alexander Hardy
      Alexander Hardy
      President & CEO
    • Brian Mueller
      Brian Mueller
      EVP & CFO
    • Cristin Hubbard
      Cristin Hubbard
      EVP & Chief Commercial Officer
    • Gregory Friberg
      Gregory Friberg
      EVP, Chief Research & Development Officer
Analysts
    • Paul Matteis
      Managing Director, Head of Therapeutics Research at Stifel Financial Corp
    • Cory Kasimov
      Senior Managing Director at Evercore
    • Tommie Reerink
      Biotech Equity Research Associate at Goldman Sachs
    • Adam Ferrari
      Biotech Equity Research Associate at J.P. Morgan
    • Akash Tewari
      Global Head - Biopharmaceutical Research at Jefferies
    • Analyst
    • Sean Laaman
      Executive Director at Morgan Stanley
    • Gena Wang
      MD - Biotech Equity Research at Barclays
    • Jasmine Fels
      Associate Analyst at UBS Group
    • Olivia Brayer
      Director & Senior Biotech Analyst at Cantor Fitzgerald
    • Kostas Biliouris
      Director - Biotech Equity Analyst at BMO Capital Markets
    • Jason Gerberry
      MD & Equity Research Analyst - Biotech & Pharma at Bank of America Merrill Lynch
    • Alexandria Hammond
      Director - Head of Therapeutics at Wolfe Research LLC
    • Ellen Horste
      Equity Research Associate at Cowen
    • Allison Bratzel
      Senior Research Analyst at Piper Sandler Companies
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