Q4 2023 Biomarin Pharmaceutical Inc Earnings Call

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Operator: Thank you for standing by, and welcome to the Biomarin Pharmaceutical fourth quarter and full year 2023 conference. I would now like to welcome Traci McCarty, Head of Investor Relations, to begin the call. Traci, over to you. Thank you, Mandeep.

Speaker Change: Thank you for standing by and welcome to the Biomarin pharmaceutical fourth quarter and full year 2023 conference call.

Speaker Change: I would now like to welcome Traci Mccarty head of Investor Relations to begin the call Tracy over to you.

Traci Mccarty: Thank you Bonnie Thank you everyone for joining us today to remind you. This non confidential presentation contains forward looking statements about the business prospects of Biomarin pharmaceutical, Inc, including expectations regarding Biomarin <unk> financial performance commercial products and potential future products in different areas of therapeutic research and.

Traci Mccarty: Thank you, everyone, for joining us today. To remind you, this non-confidential presentation contains forward-looking statements about the business prospects of Biomarin Pharmaceutical Inc., including expectations regarding Biomarin's financial performance, commercial products, and potential future products in different areas of therapeutic research and development. Results may differ materially depending on the progress of Biomarin's product programs, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market, and developments by competitors, and those factors detailed in Biomarin's filings with the SEC, such as 10Q, 10K, and 8K 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.S. GAAP, and you can find the related reconciliations to U.S. GAAP in the Earnings Release and Earnings Presentation, both of which are available on the Investor Relations section of our website.

Traci Mccarty: Development results may differ materially depending on the progress of vibrant product program actions of regulatory authorities availability of capital future actions in the pharmaceutical market developments by competitors and those factors detailed of Biomarin filings with the SEC such as 10-Q, 10-K and 8-K reports.

Traci Mccarty: 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 S. GAAP and you can find the related reconciliations to U S. GAAP in the earnings release and <unk>.

Traci Mccarty: Earnings presentation, both of which are available on the Investor Relations section of our website.

Traci Mccarty: On the call from Biomarin Management today are Alexander Hardy, President and Chief Executive Officer, Hank Fuchs, President of Worldwide R&D, and Brian Mueller, Executive Vice President, Chief Financial Officer. Jeff Ajer, Executive Vice President, Chief Commercial Officer, and Greg Geyer, Executive Vice President, Chief Technical Officer, are here with us to answer questions during the Q&A portion of the call. I will now turn the call over to Biomarin's President and CEO, Alexander Hardy. Thank you, Traci, and good afternoon, everyone. Thank you all for joining us today.

Traci Mccarty: On the call from Biomarin management today are Alexander Hardy, President and Chief Executive Officer, Hank Fuchs President of worldwide, R&D, and Brian Mueller Executive Vice President Chief Financial Officer of Asia, Executive Vice President Chief Commercial Officer, and Greg Guyer Executive Vice President Chief Technical Officer are here with us.

Traci Mccarty: To answer your questions during the Q&A portion of the call.

Alexander Hardy: I will now turn the call over to <unk>, President and CEO Alexandra Hardy.

Alexander Hardy: Thank you Tracy and good afternoon, everyone. Thank you all for joining us today.

Alexander Hardy: As I said in January and reiterate today, the opportunity at Biomarin to positively impact patients' lives through transformative therapies while delivering value-creating revenue growth and profitability to shareholders has never been or ever can be, depending on today's financial results. Total revenue grew 20% in the fourth quarter of 2023 compared to the fourth quarter of 2022. Additionally, total revenue grew 15% for the full year of 2023 compared to the prior year. This was a very strong performance. On a constant currency basis, total revenue growth was 25% in the fourth quarter and 20% for the full year. Equally as important, Biomarin's growth story of bottom-line results. Milton Gap earnings per share increased 48% in the fourth quarter versus the fourth quarter of 2022 and increased by 36% year over year.

Alexander Hardy: In January and reiterate today the opportunity at Biomarin to positively impact patients lives through transformative therapies, while delivering value, creating revenue growth profitability to shareholders.

Alexander Hardy: Never.

Alexander Hardy: Evidence.

Alexandra Hardy: Touching on today's financial results total revenue grew 20% in the fourth quarter of 2023 compared to the fourth quarter of 2022.

Alexandra Hardy: Total revenue grew 15%.

Alexandra Hardy: For year 2023 compared to the prior year. This.

Speaker Change: This is a very strong performance.

Speaker Change: On a constant currency basis total revenue growth was 25% in the fourth quarter and 20% for the full year.

Speaker Change: Equally as important to Biomarin is growth story.

Speaker Change: <unk> results.

Speaker Change: GAAP earnings per share increased 48% in the fourth quarter versus the fourth quarter of 2022 increased by 36% year over year.

Alexander Hardy: These 2023 results, along with our growth expectations as implied by our full 2024 financial guidance provided today, solidify our position as a financially self-sustaining business that can grow revenue, expand operating margins, and accelerate earnings per share. Ryan will provide more details on the financials in a moment, so I will now turn to update you on our progress on the priority I outlined in January. The first to accelerate and maximize the Boxogo opportunity remains front and center. As demonstrated by the VoxOgo financial results today, 178% growth year over year, with close to 300 new patients added in Q4, the launch in achondroplasia is on a path to blockbuster status. We were pleased that 70% of new U.S. prescriptions in Q4 were for children under the age of 5, following FDA's age expansion approval last October.

Speaker Change: These 2023 results.

Speaker Change: Loan growth expectations as implied by our full 2024 financial guidance provided today.

Speaker Change: <unk> is our position as a financially self sustaining business.

Speaker Change: Grow revenue.

Speaker Change: Spanned operating margins accelerate earnings per share.

Speaker Change: Brian will provide more details on the financials environment. So I will now turn to update you on our progress on the priorities I outlined in January.

Speaker Change: The bust to accelerate and maximize the bulks cargo opportunity remains front and center.

Speaker Change: As demonstrated by the books AGA financial results today, 178% growth year over year with close to 300, new patients added in Q4.

Speaker Change: Launched achondroplasia is on a path to blockbuster status.

Speaker Change: We were pleased that 70% new U S prescriptions in Q4 with the children under the age of five following.

Speaker Change: P H H expansion approval last October.

Speaker Change: The U S and EU approvals last quarter, allowing treatment from infancy set folks I'll go up to be a major multiyear growth driver.

Alexander Hardy: The U.S. and EU approvals last quarter allowing treatment from infancy set Foxhogo up to be a major multi-year growth driver. Beyond having an expanded age label, Boxer & Go's profile benefits from more than 1,000 patient years of long-term safety and efficacy data beyond just height. We believe this substantial clinical track record will encourage families to pursue VoxOgo treatment as early and for as long as possible to enable maximum potential therapeutic benefits. As a result of the growing global demand for VoxOvo treatment, and the scope of our extensive long-term clinical data, we're seeing an increase in the breadth of our prescriber base. Our work to build prescribing confidence and relationships with pediatric endocrinologists in the United States has been extremely well-received.

Speaker Change: Beyond having an expanded age label OXXO gas profile benefits for more than 1000 patient years of long term safety and efficacy data beyond just height.

We believe the substantial clinical track record will encourage families to pursue oxoco treatment as early.

Speaker Change: For as long as possible to enable maximum potential therapeutic benefit.

Speaker Change: As a result of the growing global demand Oxoco treatment.

Speaker Change: The scope of our extensive long term clinical data, we're seeing an increase in the breadth bulk prescriber base.

Speaker Change: A world of work to build prescribing confidence relationships with pediatric endocrinologists in the United States has been extremely well received.

Alexander Hardy: With recent Voxergo uptake for children with achondroplasia under 5 being twice as fast as launch uptake for children over 5, our plan to drive earlier and longer intervention with a goal of greater therapeutic outcomes is on track. We plan to build on our established leadership in achondroplasia treatment to expand into multiple other skeletal conditions. In the fourth quarter, Biomarin began enrollment in the six-month observational run-in portion of the pivotal program with FOXOGO for the treatment of children with hypochondroplasia. And we are actively engaging global health authorities regarding development programs for idiopathic short stature and multiple genetic short stature pathway conditions, with plans to begin pivotal studies later this year. As Hank will discuss later, we believe that there is strong proof of concept and indications beyond achondroplasia. As we expand into these indications, we hope VoxOgo treatment will empower patients and families across a spectrum of structural conditions to live their lives to the fullest. For this reason, FOXOGO acceleration, achondroplasia, and expansion into other indications remain the top priority at Biomarin. The second priority is establishing the Roktavien opportunity.

Speaker Change: With recent books logo uptake for children with achondroplasia under five being twice as fast as launch uptake.

Speaker Change: And over five are planned to drive earlier longer intervention the goal of greater therapeutic outcomes is on track.

Speaker Change: We plan to build on our established leadership in achondroplasia treatment to expand into mother into multiple other stature or conditions.

In the fourth quarter Biomarin began the enrollment.

Speaker Change: Six months observational running portion of the pivotal program with Volkswagen for the treatment of children with Hypochondria place yet and we are actively engaging global health authorities regarding development programs and idiopathic short stature at multiple genetic short stature or freight conditions with plans to begin pivotal studies later this year.

Speaker Change: Hank will discuss later, we believe that there is strong proof of concept in indications beyond achondroplasia, yet as we expand into these indications we hope Fox OCA treatment.

Speaker Change: Patients and families.

Speaker Change: Spectrum structural conditions to live their lives to the fullest.

Henry J. Fuchs: This reason folks I've got acceleration in achondroplasia and expansion into other indications remains the top priority of Biomarin.

Henry J. Fuchs: The second priority priority is establishing the rotating opportunity as I said in January we believe 2024, and 2025 will inform rotations uptake curve and long term potential.

Alexander Hardy: As I said in January, we believe 2024 and 2025 will inform Roktavien's uptake curve and long-term potential. We have been very pleased with the strong and positive payer response to the value proposition associated with Roktavien and how this has translated into published payer policies and lives covered. Furthermore, we continue to be confident with the clinical profile of the product, as evidenced by the warranty agreement, which has been equally well-received in the market. We have also continued to make good progress, activating the global market, including the recent publication of the Italian Octavian Price. We want to reiterate, however, that the complexity of aligning the required pre-infusion checklist will take time.

Henry J. Fuchs: I've been very pleased with the strong and positive payer response.

Henry J. Fuchs: Value proposition associated with <unk>.

Henry J. Fuchs: Patriot and how this has translated into published payer policies lives covered.

Furthermore, we continue to be confident with the clinical profile of the product, which is evidenced by the warranty agreement, which has been equally well received in the marketplace.

Henry J. Fuchs: We have also continued to make good progress.

Henry J. Fuchs: The global marketplace.

Henry J. Fuchs: <unk> the recent publishing of the Italian Octavian price.

Henry J. Fuchs: We wanted to reiterate however that the complexity of aligning the required pre infusion checklist will take time.

Alexander Hardy: As I outlined last month, for successful Octavian treatment, we need a motivated patient, a supportive payer, and a treatment site with a physician who's willing and able to use the product. For a pioneering new therapy, this isn't a surprise and is the reason why we intend to let the results do the talking for Octavian Update. We do expect patients to be treated with Roctavine in 2024, as implied by its inclusion in our 2024 Total Revenue Guideline. In the meantime, we will continue our work to activate the global marketplace and look forward to reporting Roktavian revenues on a quarterly basis. The third priority is our focus on the most productive R&D assets, those with transformational benefits for patients and high commercial potential. I've been spending a lot of time with the R&D team to understand the unique profile of each pipeline asset currently under development. I've been impressed by the level of innovation and expertise in developing transformational therapies.

As I outlined last month for successful Ortega and treatment, we need a motivated patient supportive payout and a treatment site with a physician who is willing and able to use the product.

Henry J. Fuchs: For a pioneering new therapy. This isn't a surprise and is the reason why we intend to let the results do the toolkit, where Octavian uptake.

Henry J. Fuchs: We do expect patients to be treated with Brookhaven and tried to stretch it for as implied bias exclusion inclusion in our 2024 total revenue guidance.

Henry J. Fuchs: In the meantime, we will continue our work to activate the global marketplace and look forward to reporting Octavian revenues on a quarterly basis.

Henry J. Fuchs: The third priority is a focus on the most productive R&D assets those with transformational benefits the patients and high commercial potential.

Henry J. Fuchs: I've been spending a lot of time with the R&D team to understand the unique profile of each pipeline asset currently under development.

Pressed by the level of innovation and expertise in developing transformational therapies.

Keeping with our ambitious financial goals, we intend to hold a very high bar in terms of disciplined spend and prioritization and most impactful medicines.

Alexander Hardy: But, in keeping with our ambitious financial goals, we intend to hold a very high bar in terms of discipline, spend, and prioritization of the most impactful medicines. To that end, we're undertaking a strategic portfolio review to determine which pipeline assets will advance and which will not. A complete update on prioritized R&D assets. Those with the highest potential patient impact and highest potential value creation for shareholders will be communicated at our Investor Day later in 2024. In the meantime, we have a number of promising candidates advancing, and Hank will provide an update on those in a moment.

Henry J. Fuchs: To that end, we are undertaking a strategic portfolio review to determine.

Henry J. Fuchs: Which pipeline assets will advance of which will not.

Henry J. Fuchs: Complete update on prioritized R&D assets, those with the highest potential patient impact and highest potential value creation shareholders will be communicated at our Investor day later in 2024.

Henry J. Fuchs: Meantime, we have a number of promising candidates advancing and Hank will provide an update on boes and environment.

Henry J. Fuchs: And lastly, our fourth priority is increasing profitability.

Henry J. Fuchs: Mr than originally planned.

Henry J. Fuchs: Our 2022 results and our full year guidance for 2024 does demonstrate our transition to growing profitability.

Alexander Hardy: And lastly, our fourth priority is increasing profitability faster than originally planned. Our 2022 results and our four-year guidance for 2024 both demonstrate our transition to growing profitability and significant operating level. Our four-year 2024 guidance reflects double-digit revenue growth regardless of Roth paid-in contributions and non-GAAP earnings per share growing faster than revenue. Bob Zogo is expected to be a major driver of year-over-year growth and is reflected in our streamlined guidance, Total Revenues Guidance Item, which includes all Biomarin commercial products, Non-Gap Operating Margin is a new line item added to Biomarin's 2024 four-year guidance, primarily because it reflects our focus on leverage across the P&L and an anticipated margin expansion this year, as well as providing you with a clear line of sight into our business, We believe these streamlined, full-year guidance items will allow you to track our financial progress as we strive to achieve the four strategic priorities I just described.

Henry J. Fuchs: Significant operating leverage.

Full year 2020 full guidance reflects double digit revenue growth, regardless of rotating contributions our non-GAAP earnings per share growing faster than revenues.

Henry J. Fuchs: So ago is expected to be a major driver of Europe, the year gross and as reflected in our streamlined guidance total revenues guidance items, which includes all biomarin commercial products.

Henry J. Fuchs: non-GAAP operating margin is a new line item to Biomarin to 'twenty to 'twenty four full year guidance, primarily because it reflects our focus of leverage across the P&L and an anticipated margin expansion. This year as well as providing you with a clear line of sight into our business performance.

Henry J. Fuchs: We believe the streamlined full year guidance items will allow you to track our financial progress as we strive to achieve the four strategic priorities I just described.

Henry J. Fuchs: So in summary, it's truly an exciting time at Biomarin and I see tremendous opportunity to create value for patients and for shareholders.

Henry J. Fuchs: Entire leadership team is hard at work on shaping the future corporate strategy, which would include views on R&D and capital allocation as well as setting and taking steps to achieve ambitious long term financial targets.

Alexander Hardy: So, in summary, it's truly an exciting time at Biomarin, and I see tremendous opportunity to create value for patients and for shareholders. The entire leadership team is hard at work shaping the future corporate strategy, which will include views on R&D and capital allocation, as well as setting and taking steps to achieve ambitious long-term financial targets. The entire organization is mobilized and approaching this work with a sense of urgency.

Henry J. Fuchs: The entire organization has mobilized and approaching this work with a sense of urgency.

Henry J. Fuchs: We will be making significant progress that we will want to share externally on a timely basis.

Henry J. Fuchs: That could be incrementally and at the Investor day for which we are evaluating specific timing.

Henry J. Fuchs: Stay tuned for additional updates.

Speaker Change: Thank you for your attention and I will now turn over the call tank.

Speaker Change: An update on key R&D highlights.

Speaker Change: Thank you Alexander and good afternoon, everyone.

Speaker Change: R&D organization is gratified by the productivity achieved on behalf of those who benefit from our innovative therapies as we take biomarin into the future and align our drug development capabilities with our ambitious financial goals. We will continue to prioritize the most high impact medicines for patients what will change is the level of spend and the rigor of the.

Henry J. Fuchs: We will be making significant progress that we will want to share externally on a timely basis. That could be incrementally and at the investor day for which we are evaluating the specific timing; please stay tuned for additional updates. Thank you for your attention, and I will now turn over the call to Hank to provide an update on key R&D highlights.

Speaker Change: Criteria used to determine which assets advance as Alexander mentioned, we are undertaking a strategic assessment of our portfolio with the goal of ranking for advertising and then advancing only those assets that represent the highest value to patients.

Henry J. Fuchs: Thank you, Alexander. And good afternoon, everyone. The R&D organization is gratified by the productivity achieved on behalf of those who benefit from our innovative therapy. As we take Biomarin into the future and align our drug development capabilities with our ambitious financial goals, we will continue to prioritize the most high-impact medicines for patients. What will change is the level of spend and the rigor of the criteria used to determine which assets advance. As Alexander mentioned, we are undertaking a strategic assessment of our portfolio with the goal of ranking, prioritizing, and then advancing only those assets that represent the highest value to patients. The assessment will evaluate the amount of time and investment required to determine proof of concept through growth through global approvals, as well as the market opportunity and competitive landscape for each asset.

The assessment, we will evaluate the amount of time and investment required to determine proof of concept through growth through global approvals as well as the market opportunity and competitive landscape for each asset.

Speaker Change: A higher bar is designed to expedite development increase the probability of success and improve cost effectiveness. We look forward to sharing the results of the strategic investment assessment at our Investor Day later in 2024.

Speaker Change: Touching briefly on a few clinical updates we intend to open the treatment study of the pivotal trial with ochsner for HEICO contemplation in the middle of this year.

Speaker Change: Results from Doctor Jobbers, 52 week Phase II study with Vac said, though in hypochondria pleasure. We're recently posted to the <unk> website ahead of his oral presentation at the meeting in Toronto next month.

Speaker Change: We are encouraged to see an increase in the 12 months annualized growth velocity of 1.81 centimeters inbox soup oxoco treated children.

Speaker Change: With hypochondriac, leisure and <unk> and a safety and sustained durability profile observed in achondroplasia at six months and 12 months. These data provide further support for our imminent plans to initiate the treatment phase of our pivotal program and hypo contemplation expected to begin in mid 'twenty four regard.

Henry J. Fuchs: A higher bar is designed to expedite development, increase the probability of success, and improve cost effectiveness. We look forward to sharing the results of the strategic assessment at our Investor Day later in 2024. Touching briefly on a few clinical updates, we intend to open the treatment study of the pivotal trial with VoxOgo for hypochondroplasia in the middle of this year. Results from Dr. Dauber's 52-week Phase 2 study with VoxOgo and hypochondroplasia were recently posted to the ACMG website ahead of his oral presentation at the meeting in Toronto next month. We are encouraged to see an increase in the 12-month annualized growth velocity of 1.81 centimeters in Voxoco-treated children treated with hypochondroplasia and a safety and sustained durability profile observed in achondroplasia at 6 months and 12 months.

Speaker Change: Our development programs in idiopathic short stature and multiple genetic short stature pathway conditions. We are in discussions with global health authorities with plans to begin pivotal studies later this year, we look forward to Dr. Divers ISS update at the pediatric Endocrine Society meeting in May Biomarin of securing our leadership.

Speaker Change: <unk> for treating multiple genetic central conditions, and we look forward to updating you on our progress.

Speaker Change: Across the three pivotal programs just described.

Speaker Change: Briefly to other assets in the early stage pipeline, we're pretty pleased to share that the phase II proof of concept study at being around $3 51 for the treatment of Duchenne muscular dystrophy is open for enrollment.

Speaker Change: The 52 week study will enroll 18 boys with Duchenne muscular dystrophy with a potential to expand enrollment as needed and is designed to assess both dystrophin levels and functional measures.

Henry J. Fuchs: These data provide further support for our imminent plans to initiate the treatment phase of our pivotal program in hypochondroplasia expected to begin in mid-24. Regarding our development programs in idiopathic short stature and multiple genetic short stature pathway conditions, we are in discussions with global health authorities with plans to begin pivotal studies later this year. We look forward to Dr. Dauber's ISS update at the Pediatric Endocrine Society meeting in May. Biomarin is securing our leadership position for treating multiple genetic statural conditions, and we look forward to updating you on our progress across the three pivotal programs just described. Turning briefly to other assets in the early stage pipeline, we're pleased to share that the Phase II proof-of-concept study of BMN 351 for the treatment of Duchenne muscular dystrophy is open for enrollment. The 2022 study will enroll 18 boys with Duchenne muscular dystrophy, with the potential to expand enrollment as needed, and is designed to assess both dystrophin levels and functional measures. BMN349 is an early bioavailable small molecule designed for the treatment of alpha-1 antitrypsin deficiency liver disease.

Speaker Change: And then 349 is an orally bio available small molecule designed for the treatment of Alpha one antitrypsin deficiency liver disease are non clinical studies indicate $3 49 enables accretion of the mutant protein and prevents its preliminary <unk> in liver cells, which if unchecked drives the progression of liver disease or <unk>.

Speaker Change: Ascending dose study in healthy human volunteers is progressing with no safety signals observed thus far we look forward to providing an update on our other pipeline assets. Following the strategic assessment described by Alexander.

Alexander Hardy: Thanks for your attention. Thanks for your support and I will now turn the call over to Brian for financial updates.

Brian Mueller: Thank you Henk. Please refer to today's press release summarizing our financial results for full details on the fourth quarter and full year 2023 <unk>.

Brian Mueller: Including reconciliations of GAAP to non-GAAP financial measures.

Brian Mueller: I will provide my comment on a GAAP basis for 2023 results and comment on key financial updates and guidance for 2024.

Brian Mueller: Our 2023 financial results will be available in our upcoming Form 10-K, which we expect to file within the next few days.

Brian Mueller: In the fourth quarter of 2023, Biomarin generated strong total revenue up $646 million rep.

Brian Mueller: Representing 20% year over year growth, including Kuban and 26% growth excluding Kuban.

Brian Mueller: As expected the strength of our enzyme products generated more than one $7 billion net product revenues for the full year 2023, an increase of 4% year over year.

Brian Mueller: Our non-clinical studies indicate 349 enables secretion of the mutant protein and prevents its polymerization in liver cells, which if unchecked, drives the progression of liver disease. The single ascending dose study in healthy human volunteers is progressing with no safety signals observed thus far. We look forward to providing an update on our other pipeline assets following the strategic assessment described by Alexandra. Thanks for your attention. Thanks for your support. And I will now turn the call over to Brian for financial matters, Ryan. Thank you, Hank.

Brian Mueller: Looking more closely at performance in the fourth quarter <unk> revenues of $146 million represented 118% quarter over quarter growth. We've previously discussed the supply constraint on box sogo revenue in 2023.

Brian Mueller: Our plans for supply to satisfy forecasted commercial demand around the middle of this year remain intact and our fourth quarter revenue result, being higher than guidance was driven by some incremental supply that became available late in the quarter.

Brian Mueller: Double digit revenue growth of both Vimizim and pallet Zika in the fourth quarter was partially offset by anticipated lower Kuban revenues and were also an important contributor to total revenues exceeding $2 $4 billion for the full year 2023 and in line with our expectations.

Brian Mueller: Please refer to today's press release summarizing our financial results for full details on the fourth quarter and full year 2023, including reconciliations of gap to non-gap financial results. I will provide my comments on a gap basis for 2023 results and will comment on key financial updates and guidance for 2024. All 2023 financial results will be available in our upcoming Form 10-K, which we expect to file within the next few days. In the fourth quarter of 2023, Biomarin generated strong total revenue of $646 million, representing 20% year-over-year growth, including Kuvan, and 26% growth excluding Kuvan. As expected, the strength of our enzyme products generated more than $1.7 billion of net product revenues for the full year 2023, an increase of 4% year over year. Looking more closely at performance in the fourth quarter, Boxogo revenues of $146 million represented 118% quarter-over-quarter growth. We've previously discussed the supply constraint on Voxogo revenue in 2023. Our plans for supply to satisfy forecasted commercial demand around the middle of this year remain intact.

Brian Mueller: R&D expenses in the fourth quarter were $206 million up.

Brian Mueller: $34 million year over year, primarily due to increased early stage research activities as well as increased activity in our clinical programs.

Brian Mueller: SG&A expense in the fourth quarter with $275 million.

Up $29 million from last year. Please note we had a number of unique expenses during the fourth quarter of 2023, including impairment charges related to the discontinuation of our first generation box yoga pen.

Brian Mueller: The devaluation of the Argentinean peso.

Brian Mueller: Along with incremental G&A expense related to corporate governance matters and leadership transitions together. These items combined to total over $40 million in Q4 2023.

Brian Mueller: Moving to the bottom line GAAP net income for the fourth quarter was $24 million contributing to $168 million of GAAP net income for the full year, representing GAAP diluted earnings per share of <unk> 87 per share.

Brian Mueller: GAAP net income for the fourth quarter was also impacted by the recognition of a loss at an impairment recorded in the other income and expense line.

Brian Mueller: You'll note that on taxes similar to the third quarter, we recognized some incremental discrete tax benefits in the fourth quarter that lowered our effective tax rate for the full year. We continue to project on a consolidated global level, an effective tax rate in the low twenties for 2024 and beyond.

Brian Mueller: And our fourth quarter revenue result being higher than guidance was driven by some incremental supply that became available late in the quarter. Double-digit revenue growth of both Vimazim and Palanzec in the fourth quarter was partially offset by anticipated lower Kuvan revenues, and we're also an important contributor to total revenues exceeding $2.4 billion for the full year 2023 and in line with our expectations. R&D expenses in the fourth quarter were $206 million, up $34 million year-over-year, primarily due to increased early-stage research activities, as well as increased activity in our clinical program. SG&A expenses in the fourth quarter were $275 million, up $29 million from last year.

Brian Mueller: non-GAAP income for the fourth quarter with $95 million and 400 $405 million for the full year, representing full year non-GAAP diluted EPS of $2 and <unk> <unk> per share and growth over 36% over 2022.

Brian Mueller: As we move into 2024. Please note that there are select changes and Biomarin P&L geography, becoming effective in 2024, we are expecting to classify foreign currency revaluation and other income and expense going forward instead of its prior classification within SG&A expense.

Brian Mueller: And the idle plant time related costs will be classified in cost of sales going forward instead of their prior classification within SG&A expense. These changes, which again our classification only and do not impact the bottom line are being made to provide greater clarity on our core operating results.

Brian Mueller: Please note, we had a number of unique expenses during the fourth quarter of 2023, including impairment charges related to the discontinuation of our first-generation box logo and the devaluation of the Argentinian peso, along with incremental GNA expenses related to corporate governance matters and leadership transition. Together, these items combined for a total of over $40 million in Q4 2023. Moving to the bottom line, GAAP net income for the fourth quarter was $20.4 million, contributing to $168 million of GAAP net income for the full year, representing GAAP diluted earnings per share of 87 cents per share. The gap in that income for the fourth quarter was also impacted by the recognition of a loss and an impairment recorded in other income and expenses.

Brian Mueller: As to better align with industry peers.

Brian Mueller: Details of the revised presentation of idle plant costs and foreign exchange gains and losses for previously reported 2023, and 2022 periods to conform with the presentation that we'll use going forward are available on our website.

Brian Mueller: As Alexander mentioned for 2024, we are guiding to total revenues non-GAAP operating margin and non-GAAP diluted earnings per share for.

Brian Mueller: For the full year 2020 for total revenues, we expect between $2 7 billion and $2 8 billion, which.

Brian Mueller: Which at its midpoint represents approximately 14% growth compared to 2023.

Brian Mueller: I will note that on taxes, similar to the third quarter, we recognized some incremental discrete tax benefits in the fourth quarter that lowered our effective tax rate for the full year. We continue to project, at a consolidated global level, an effective tax rate in the low 20s for 2024 and beyond. Non-GAAP income for the fourth quarter was $95 million and $405 million for the full year, representing full-year non-GAAP diluted EPS of $2.08 per share and growth of over 36% over 2022.

Brian Mueller: To provide some additional context since this is the first time that we are not guiding to specific brand revenues. Our 2020 for revenue guidance is driven by continued strong growth in <unk> with expansion into younger age groups being a key driver of anticipated 2020 for new patient starts mid to high single digit growth across.

Brian Mueller: Five brands in our E. R T portfolio and offset by the continued decline of two van due to the loss of market exclusivity.

While we're Octavian is definitively included in our total revenue forecast the revenue contribution from Octavian is relatively modest and risk adjusted based on our recent experience going forward, we will let the actual rack TVN results speak to the performance.

Brian Mueller: As we move into 2024, please note that there are select changes in Biomarin's P&L geography becoming effective in 2024. We are expecting to classify foreign currency revaluations and other income and expense going forward instead of its prior classification within SG&A, and idle plant time-related costs will be classified in cost of sales going forward instead of their prior classification within SG&A expense. These changes, which again are classification only and do not impact the bottom line, are being made to provide greater clarity on our core operating results, as well as to better align with industry peers. Details of the revised presentation of idle plant costs and foreign exchange gains and losses for previously reported 2023 and 2022 periods to conform with the presentation that we'll use going forward are available on our website. As Alexander mentioned, for 2024, we are guiding to total revenue. Non-Gap Operating Margin and Non-Gap Diluted Earnings Per Share For the full year 2024, total revenues, we expect between $2.7 billion and $2.8 billion, which at its midpoint represents approximately 14% growth compared to 2023.

Brian Mueller: Also one comment specific to the first quarter of 2024 Z that we are expecting a Q4 to Q1 dynamic with respect to order timing and volumes whereby Q4 included some modest incremental revenue that will impact Q1 growth we stand behind full year 2020 for total revenue.

Brian Mueller: Guidance provided today and we expect most of the 'twenty 'twenty four total revenue growth to be weighted to the second half of the year.

With respect to non-GAAP operating margin for the full year 2024, we are guiding to between 23% and 24%, which represents four percentage points of expansion versus the 2023 non-GAAP operating margin of 19, 4%. This is inclusive of our G&A rats reclassifications.

Brian Mueller: <unk> that I just mentioned.

Brian Mueller: Over the last three years, including through our 2024 guidance. Our non-GAAP operating margin is projected to increase by approximately 13 percentage points from approximately 10% in 2021 to 23.5 midpoint of our 2024 guidance. This demonstrates our.

Brian Mueller: <unk> to growing profitability. However, it is not the end of the story as we are working through our cost efficiency and resource allocation priorities to help set ambitious long term financial targets to compete to be communicated this year.

Brian Mueller: And for non-GAAP diluted earnings per share, we expect between $2 60, and $2 80 per share for the full year 2024, which at the midpoint represents 30% growth over last year.

Brian Mueller: To provide some additional context, since this is the first time that we are not guiding to specific brand revenues, our 2024 revenue guidance is driven by continued strong growth in VoxOgo, with expansion into younger age groups being a key driver of anticipated 2024 new patient starts, mid-to-high single-digit growth across the five brands in our ERT portfolio, and offset by the continued decline of QVAN due to the loss of market exclusivity. While Roktavian is definitively included in our total revenue forecast, the revenue contribution from Roktavian is relatively modest and risk-adjusted based on our recent experience. Going forward, we will let the actual Roktavian results speak for themselves.

Brian Mueller: As we move into the next chapter of Biomarin, we are executing on our growth strategy with impressive performance driven by box that will go into Contra plays.

Brian Mueller: The new indication.

Brian Mueller: A durable and growing enzyme products business and the potential to realize the value of our IP.

Thank you for your continued support and we will now open up the call to your questions operator.

Speaker Change: The floor is now open for your questions to ask a question at this time simply press the star followed by the number one on your telephone keypad.

Speaker Change: We ask that you. Please limit yourself to one question, we'll now take a moment to compile a roster.

Speaker Change: Our first question comes from the line of Salvia Richter with Goldman Sachs. Please go ahead.

Salveen Richter: Good afternoon, Thanks for taking my question.

Brian Mueller: Also, one comment specific to the first quarter of 2024 is that we are expecting a Q4 to Q1 dynamic with respect to order timing and volumes, whereby Q4 includes some modest incremental revenue that will impact Q1 growth. We stand behind full year 2024 total revenue guidance provided today, and we expect most of the 2024 total revenue growth to be weighted to the second half of the year. With respect to the non-gap operating margin for the full year 2024, we are guiding to between 23% and 24%, which represents four percentage points of expansion versus the 2023 non-gap operating margin of 19.4%.

Salveen Richter: Just wanted to.

Salveen Richter: Better understand your EPS guidance.

Salveen Richter: Q4, and what that is and are there.

Salveen Richter: Opex.

Salveen Richter: And.

Overall R&D cuts that are.

Salveen Richter: Basically baked into the assumptions there and help US also understand as you do your strategic portfolio review of the R&D program.

Salveen Richter: Quite sure yet.

Salveen Richter: Further investment in advance thankful.

Salveen Richter: Yes. Thanks Alvin this is Brian appreciate the question.

Brian Mueller: So first of all.

Brian Mueller: Please that the non-GAAP EPS guidance midpoint implies 30% growth.

Brian Mueller: Over this year and this year as noted was over 30% growth over 2022.

Brian Mueller: There are a few items that impact the year over year non-GAAP analysis.

Brian Mueller: One is those.

Brian Mueller: Some of those tax benefits that I mentioned in 2023, so now that tax since the beginning of 'twenty three is in our non-GAAP income to the extent those benefits don't recur that would be a headwind if you will to 2024 non-GAAP.

Operator: This is inclusive of the GNA reclassifications that I just mentioned. Over the last three years, including through our 2024 guidance, our non-gap operating margin is projected to increase by approximately 13 percentage points, from approximately 10% in 2021 to the 23.5 midpoint of our 2024 guidance. This demonstrates our commitment to growing profitability. However, it is not the end of the story, as we are working through our cost efficiency and resource allocation priorities to help set ambitious long-term financial targets to be communicated this year. And for non-GAAP diluted earnings per share, we expect between $2.60 and $2.80 per share for the full year 2024, which at the midpoint represents 30% growth over last year. As we move into the next chapter of Biomarin, we are executing on our growth strategy with impressive performance driven by Voxelgo and Achondroplasia in pursuit of new indications of durable and growing enzyme products business and the potential to realize the value of Thank Operator. The floor is now open for your questions. To ask a question at this time, simply press the star followed by the number one on your telephone keypad.

Brian Mueller: Theres also some unique I mentioned the unique SG&A charges in in 'twenty three we got some incremental SG&A in 'twenty four we're implementing a new ERP system, which is a commanding some some G&A resources in 'twenty four.

Brian Mueller: So those are some of the dynamics into the part of your question about how much of our strategic savings or cost efficiency opportunities are included.

Brian Mueller: Just a modest amount of the known items at this point that we were already working on.

Brian Mueller: We are embarking on the cost efficiency and operating model efficiency.

Brian Mueller: Export exploration as we speak this is going to be part of the more ambitious financial targets setting for the future to be communicated later this year. So I'll ask you to stay tuned on that part, but I will say that there's not a substantial.

Brian Mueller: Mt.

Brian Mueller: Savings related to that in this guide.

Brian Mueller: I saw being in response to the second question about the prioritization of the R&D portfolio. We are undertaking a strategic assessment of our portfolio with the goal of ranking prioritizing and advancing only those assets that represent the highest value to patients and shareholders.

Brian Mueller: The assessment will include considerations of time and money.

Brian Mueller: To prove concept or to advance to global approvals as the case may be as well as consideration of the market opportunity and competitive landscape and the concept of having a very high bar for going forward is to foster expedited development when things happen early that are impressive and import.

Salveen Richter: We ask that you please limit yourself to one question. We'll now take a moment to compile our raw data. Our first question comes from the line of Salveen Richter with Goldman Sachs. Please go ahead. Good afternoon.

Brian Mueller: Thanks for taking my question. I just wanted to better understand your EPS guidance for 2024 and what that assumes. Are there some off-expenses and, you know, overall R&D cuts that are basically baked into the assumptions there? And help us also understand, as you do your strategic portfolio review of the R&D program, what the criteria is for further investment and advancement. Thank you. Yeah, thanks, Salveen. This is Brian.

Brian Mueller: Subsequent development and registration and market access happens much more quickly and so with those higher bars. We can also see.

Brian Mueller: That subsequent events have higher probability of success and also contribute to improving the cost effective disapproved grams. We look forward to sharing the results of the strategic investments later in 2024.

Brian Mueller: Okay.

Costa Worry: Our next question comes from the line of a cost to worry with Jefferies. Please go ahead.

Brian Mueller: Appreciate the question. So, first of all, you know, we're pleased that the non-GAAP EPS guidance midpoint implied 30% growth over this year. And this year, as noted, was over 30% growth over 2022. There are a few items that impact the year-over-year non-GAAP analysis.

Cost: Hey, thanks, so much.

Cost: Peter in the past by them and spend a lot of time and resources building up its gene therapy capabilities, but we haven't really seen that translate to shareholder value. For example, it looks like youre spending almost identical amount on box Hogan rock gaming, but with different results. What are your thoughts on potentially divesting your gene therapy platform or even rock caving in order to cut costs and focus the story is that <unk>.

Brian Mueller: One is some of those tax benefits that I mentioned in 2023. So now that tax since the beginning of 23 is in our non-GAAP income, to the extent those benefits don't recur, that would be a headwind, if you will, to 2024 non-GAAP. There are also some unique charges. I mentioned the unique SG&A charges in 2023.

Speaker Change: Out of the question in your mind.

Cost: Okay.

Speaker Change: Thanks very much for the question.

Speaker Change: As I mentioned in terms of our priorities, we're still very much at the early stage with rux avian we already want to establish the opportunity to see that we.

Speaker Change: We are seeing progress in terms of market access market activation.

Speaker Change: So we wanted to see that.

Speaker Change: Run through.

Speaker Change: 2024, we also I'd say probably into 2025 is when we'll be able to really determine.

Brian Mueller: We've got some incremental SG&A in 24. We're implementing a new ERP system, which is commanding some G&A resources in 24. So those are some of the dynamics.

Speaker Change: In the meantime.

Speaker Change: We are spending wisely and cautiously supporting the launch.

Speaker Change: But.

Brian Mueller: And to the part of your question about how much of our strategic savings or cost efficiency opportunities are included, just a modest amount of the known items at this point that we were already working on. We are embarking on the cost efficiency and operating model efficiency exploration as we speak. This is going to be part of the more ambitious financial targets setting for the future to be communicated later this year. So we'll ask you to stay tuned on that part. But I will say that there's not a substantial amount of savings related to that in this guide.

Speaker Change: We're very mindful of the return on investment that we're currently seeing from.

Speaker Change: We will take it.

Speaker Change: Same time, we referenced in this conversation today.

Speaker Change: Strategic review so we're also thinking about the future strategy of Biomarin, we're looking at the R&D portfolio.

Speaker Change: We're looking at our own experience with with gene therapy.

Speaker Change: Scientific challenges regulatory market access bucket.

Speaker Change: Bucket uptake.

And also taking note of what's happening in the world ex side Biomarin tools.

Henry J. Fuchs: Hi Salveen, in response to your second question about prioritizing the R&D portfolio, we're undertaking a strategic assessment of our portfolio with the goal of ranking, prioritizing, and then advancing only those assets that represent the highest value to patients and shareholders. The assessment will include considerations of time and money involved in proving the concept or to advance to global approvals, as the case may be, as well as consideration of market opportunity and competitive landscape. The concept of having a very high bar for going forward is to foster expedited development. When things happen early that are impressive and important, subsequent development, and registration, and market access happen much more quickly. And so with those higher bars, we can also see that subsequent events have a higher probability of success and also contribute to improving the cost effectiveness of programs.

Speaker Change: And as part of that we will assess do we have the right exposure to gene therapies in our pipeline.

Speaker Change: Is it something we want to double down on stay well stay the course.

Speaker Change: Take a lower exposure to gene therapy. So we'll continue to keep you updated will provide more information.

Speaker Change: At our Investor Day later this year.

Speaker Change: Our next question comes from the line of Jessica Fye with J P. Morgan. Please go ahead.

Jessica Fye: Great. Good afternoon, Thanks for taking my questions a couple of Inbox sogo.

First.

Jessica Fye: On the financial side you mentioned.

Jessica Fye: <unk> revenue I think you are seeing sort of broadly for key revenue reflected modest incremental revenue that would impact <unk> growth can you talk to whether the <unk> box they'll go number specifically benefited from any channel inventory changes are lumpy international orders and if so just quantify.

Jessica Fye: What was out of the ordinary.

Jessica Fye: And then on the pipeline side.

Speaker Change: Can you.

Speaker Change: Two basket trials with multiple indications for some of these additional potential of OXXO, though development areas.

Speaker Change: Yes.

Speaker Change: How likely is the FDA or other regulators to sign up on this.

Speaker Change: We like that type of approach. Thank you.

Henry J. Fuchs: We look forward to sharing the results of the strategic investments later in 2024. Our next question comes from a line from Akash Tewari with Jeffreys. Please go ahead. Hey, thanks so much. Alexander, in the past, Biomarin spent a lot of time and resources building up its gene therapy capabilities, but we haven't really seen that translate to shareholder value. For example, it looks like you're spending almost identical amounts on Voxovan or Octavian, but with different results. What are your thoughts on potentially divesting your gene therapy platform or even Octavian in order to cut costs and focus the story? Is that option out of the question in your mind?

Speaker Change: Hey, Jess it's Brian Thanks, I'll take the first part of your question.

Brian Mueller: Good question and the word.

Brian Mueller: To respond us.

Brian Mueller: Nothing excessive with respect to the channel and nothing broad across the marketplaces.

Brian Mueller: Made that comment because when we gave our.

Brian Mueller: Full year guide essentially Q4 guide back on the first of November the high end was $455 million and we talked about how that high end was supply constrained.

Brian Mueller: And so here, we are reporting close to $470 million for the quarter. So I wanted to explain that the circumstances. There were some additional commercial supply that became available. So we used it to meet demand that was out there and the point is that with respect to Q1.

Brian Mueller: We don't necessarily.

Brian Mueller: Specter guarantee that that same dynamic can recur. So that's the Q4 Q1 dynamic.

Alexander Hardy: Thanks. Thanks very much for the question. You know, as I mentioned, in terms of our priorities, we're still very much at the early stage with Roktavion. We really want to establish the opportunity there. We are seeing progress in terms of market access and market activation. So we want to see that through.

Alexander Hardy: 2024; we also think probably into 2025 is when we'll be able to really determine it. In the meantime, we're spending wisely and cautiously, supporting the launch, but, you know, we're very mindful of the return on investment that we're currently seeing from Roktavia. At the same time, we referenced in this conversation today a strategic review, so we're also thinking about the future strategy of Biomarin. We're looking at the R&D portfolio. We're looking at our own experience with gene therapy, the scientific challenges, and regulatory market access. Market Uptake, and also taking note of what's happening in the world outside Biomarin. And as part of that, we'll assess, do we have the right exposure to gene therapies in our pipeline? Is it something we want to double down on, stay the course, or take a lower exposure to gene therapies?

Alright Theater studies baseline run in studies that are essential for enrolling these baskets of studies and so that we can expedite the start and completion of these additional registration activities. So uhm and some I think we're trying to be as clever as we can be about getting.

Alexander Hardy: So we'll continue to keep you updated. We'll provide more information at our investor day later this year. Our next question comes from the line of Jessica Fye with J.P. Morgan. Please go ahead. Great. Good afternoon. Thanks for taking my questions. A couple on VoxOgo.

Brian Mueller: These studies under way in working with health status around the world to ensure that they meet the demands of regulators.

Speaker Change: Thank you.

Speaker Change: Our next question comes from the line of film that though with T. D. Cowan. Please go ahead.

Speaker Change: Thanks for taking my question follow up question on Vox ago in the past Barbara and had talked about converting box O goes approval from accelerated to fall in that potentially changing what would be necessary for the competition to.

Henry J. Fuchs: First, on the financial side, you mentioned 4Q revenue. I think you're seeing sort of broadly 4Q revenue reflected modest incremental revenue that would impact 1Q growth. Can you talk about whether 4Q VoxOgo... benefited from any channel inventory changes or not? Thank you all for joining us today, and you. For some of these additional potential Voxelgo development areas, how likely is the FDA or other regulators to sign off on that type of approach? Hey Jeff, it's Brian.

Speaker Change: To be approved is there any update on the process of converting Fox that goes with approval to fall and at this point would it have any impact on.

Speaker Change: The regulatory requirements for the potential competition, that's that's a pivotal studies already.

Speaker Change: <unk>.

Speaker Change: I fell no particular update on the regulatory status or strategy or read through on competitors. The one of the things that's really exciting about update that we can report is that every so often we look at ongoing studies to assess the durability of of.

Brian Mueller: Thanks. I'll take the first part of your question. Good question.

Speaker Change: Fox of those affected me continued to be reassured that boxer ago. Unlike other growth promoting types of drugs.

Brian Mueller: And the way I'd respond is nothing excessive with respect to the channel and nothing broad across the marketplaces. I made that comment because when we gave our, the high-end was $455 million, and we talked about how that high-end was supply-constrained. And so here we are, you know, reporting close to $470 million for the quarter.

Speaker Change: Been remarkable benefit of sustaining its effect and and that's really one of the key features of benefit of of of that size or for patients and and I think it's gonna be an important bar for any future innovation in the space to ensure that patients can zoom physiologically.

Speaker Change: Normal growth rate safely and through the entire period of their growth starting from earliest diagnosis all the way through the closure of the growth plate.

Brian Mueller: So I wanted to explain that in the circumstances, there was some additional commercial supply that became available, so we used it to meet demand that was out there. And the point is that, with respect to Q1, we don't necessarily expect or guarantee that that same dynamic can recur. So that's the Q4, Q1 dynamic. You know, that plus decreasing Kuvan in Q1 is just an overall comment that Q1 is not going to be our strongest quarter.

Speaker Change: So.

Speaker Change: Good on box I go so far.

Speaker Change: Perfect. Thank you.

Geoff Meacham: Our next question comes from Jeff medium with the Bank of America. Please go ahead.

Jeff: Hey, guys afternoon. Thanks for the question another one on box. So I'll go you know and I know, what the centerpiece of growth and and the pipeline the major pipeline investment for the year and beyond but I wanted to ask you what's been the impact of your commercial investments so far in terms of.

Henry J. Fuchs: And we're going to see most of the growth in the second half of the year. Thanks, Jessica. As regards the concept of the basket, you know, one of the great benefits of having Dr. Dauber do his study is that we actually have really good regulatory feedback on that question already. And in fact, you can see that his study is itself a basket of things that might be formally known as subsets of idiopathic short stature or hypochondroplasia.

Speaker Change: The pace of new starts or broaden the prescriber base looking into the second half of last year and then what do you think about what does success look like for 2025, I'm just trying to figure out a couple of metrics that we can kind of evaluate over the course of this year <unk>. Thank you.

Speaker Change: Yes, it's Jeff here, let me take a shot of that so I think we've had some good returns on our commercial investments today, you mentioned new starts.

Jeff: New starts where accelerated starting late last year following the label expansion.

Henry J. Fuchs: So the concept of basketing has already been in front of the FDA and has already gained a little bit of acceptance. And having said that, though, as reflected in our prepared comments, we are in the stages of finalizing our game plan after our last interactions with health authorities around the world. And we'll communicate final design decisions when those studies come online. But we're not waiting for any of that because we're also implementing our feeder studies, the baseline run-in studies that are essential for enrolling these baskets of studies. So, in sum, I think we're trying to be as clever as we can be about getting these studies underway and working with health authorities around the world to ensure that they meet the demands of regulators.

Speaker Change: Noted in the prepared remarks.

Jeff: Expanding the prescriber base, particularly in the United States to to <unk>.

Jeff: Hatrick endocrinologist as a particular area of focus both last year and ended this year, we're making good progress and in terms of metrics.

Jeff: I would I would say, we're dialing back from specific quantitative metrics on these launches and turning more towards revenue I might suggest said with a with a post launch revenue base for box I'll go in particular, the best Man.

Jeff: Trick I would recommend now and going forward is the revenue line.

Speaker Change: Great. Thank you.

Speaker Change: Our next question comes from the line Alley Murley was UBS financial Please go ahead.

Henry J. Fuchs: Our next question comes from the line of Phil Nadeau with TD Cowan. Please go ahead. Thanks for taking our question. A follow-up question on VoxFogo. In the past, Biomarin had talked about converting VoxFogo's approval form accelerated to full and that potentially changing what would be necessary for the competition to be approved. Is there any update on the process of converting FOXOGO's approval form to full

Alley Murley: Hey, guys. Thanks for taking my question at the ISS.

Alley Murley: <unk>, you mentioned will be coming in now.

Alley Murley: Can we expect from that in terms of the patient numbers and what you're looking to see and then just as you look across the many different sharks Patrick conditions are you thinking about prioritization across the indications in which he'd move forward.

Alley Murley: Any facial begins advocacy.

Henry J. Fuchs: And at this point, would it have any impact on the regulatory requirements for the potential competition that's in pivotal studies already? Thanks. Hi Phil.

Speaker Change: Okay Uhm S. S encourage Dr drivers ISS anticipated update analysis and study and so it's very much under his determination as to what he's going to update my understanding is that he's enrolled more hypochondriac place your patience than other indications, but I think he would.

Henry J. Fuchs: No particular update on the regulatory status or strategy or read through on, you know, competitors, but one of the things that's really exciting about the update that we can report is that every so often we look at ongoing studies to assess the durability of Voxogo's effect, and we continue to be reassured that Voxogo, unlike other growth-promoting types of drugs, has this remarkable benefit of sustaining its effect, and that's really one of the key features of benefit of Voxogo for patients, and I think is going to be an important bar for any future innovation in this space to ensure that patients can resume a physiologically normal growth rate safely and through the entire period of their growth, starting from earliest diagnosis all the way through the closure of the growth plate. So. Good on VoxOgo so far.

Speaker Change: Be reporting unless he felt that there was useful information to be reported I think the things to be looking for really are corroboration of what I think most scientists fundamentally believe which is that C. N P. As a master regulator, a bone growth is gonna rock across a wide variety of indications and so.

Speaker Change: We had seen with a hypochondriac pleasure program. So that's actually the sort of the first half of the cohort at the six month Mark that enabled F. D. A to gain confidence that we could go directly into phase three and that's predicated on a lot of this biology, and therefore I think the important outcome of the ISS.

Operator: Perfect, thank you. Our next question comes from Geoff Meacham with Bank of America. Please go ahead. Hey guys, afternoon.

Speaker Change: <unk> P. S is gonna be are we saying basically the same effects that we expect to see you know and the different types of stature on disorders.

Geoffrey Meacham: Thanks for the question. Another one on Voxelgo, you know. I know it's a centerpiece of growth and the pipeline, the major pipeline investment for the year beyond. But I want to ask you, what's been the impact of your commercial investments, you know, so far in terms of the pace of new starts or broadening the prescriber base, looking into the second half of last year? And then what do you think about what success looks like for 2025? I'm just trying to figure out a couple of metrics that we can kind of evaluate over the course of this year for Voxelgo. Thank you. Hi Geoff, it's Geoff here. Let me take a shot of that.

Speaker Change: And as regards your second question I think the prioritization process has been described it really boils down to fairly conventional metrics around time and cost to proof of concept or to global registration value that gets created for patients and for shareholders with the idea.

Speaker Change: By sending a high bar for something like proof of concept then you really only advance your winters and by by focusing on does we hope that will expedite development and bring faster and higher value to patients and shareholders.

Jeffrey Robert Ajer: So I think we've had some good returns on our commercial investments today. You mentioned new starts. We're accelerating, starting late last year, following the label expansion, as noted in the prepared remarks. Expanding the prescriber base, particularly in the United States, to pediatric endocrinologists, is a particular area of focus, both last year and into this year.

Speaker Change: The undertaking.

Speaker Change: Our next question comes from the line of Joseph Schwartz was Leerink partners. Please go ahead.

Joseph P. Schwartz: [noise] great. Thank you very much and welcome Alexander I think I heard you say that the outcomes of the strategic and operating review committee could be communicated incrementally as well as the Investor day in the third quarter. So I was wondering if you have a sense of which updates might emerge sooner than which nothing could require.

Jeffrey Robert Ajer: We're making good progress. And in terms of metrics, I would say we're dialing back from specific quantitative metrics on these launches and turning more towards revenue. I might suggest that with a post-launch revenue base for Voxelgo in particular, the best metric I would recommend now and going forward is the revenue line.

Joseph P. Schwartz: What kinds of furniture.

Speaker Change: [noise]. Thanks, Joseph Thanks, very much to the the question.

Speaker Change: <unk> S. O C is proceeding extremely well we've met frequently women, making progress on the.

Speaker Change: Central guidance longterm financial guidance and the capital allocation.

Speaker Change: A strategy.

Jeffrey Robert Ajer: Thanks. Our next question comes from the line of Ellie Merle with UBS Financial. Please go ahead. And, hey guys, thanks for taking the question. The ISS FOXOGO data update you mentioned will be coming in May. What should we expect from that in terms of the patient numbers and what you're looking to see? And then just as you look across the many different short stature conditions, how are you thinking about prioritizing across the indications and which you'd move forward versus not and any thresholds in terms of efficacy? Okay, as regards Dr. Dauber's anticipated update on the ISS, you know, this is his study, and so it's very much under his determination as to what he's going to update. My understanding is that he's enrolled more hypochondroplasia patients than other indications, but I think he wouldn't be reporting unless he felt that there was useful information to be reported.

Speaker Change: We also have a lot of other work underway as you as you get a sense from <unk>.

Speaker Change: Dr optimization.

Speaker Change: Celebration of Fox R got even foster R&D prioritization.

Speaker Change: Et cetera et cetera.

Speaker Change: And right now with with figuring out what is the best timing to update.

Speaker Change: The external world on our progress on these points.

Speaker Change: Obviously, the the benefit of the invest today just allows us to put this all together with a strategic.

Speaker Change: Context of where are we gonna take by them right into the future at the same time, we're keen to share the information we can as soon as we can on the progress we're making so.

Speaker Change: As I said in my prepared remarks, please stand by for more information.

Speaker Change: The latest possible they will be best today for all of those.

Speaker Change: <unk>.

Speaker Change: If it makes sense will communicate other information sooner.

Speaker Change: Okay.

Speaker Change: Our next question comes from the line of Robyn <unk> was true Securities. Please go ahead.

Henry J. Fuchs: I think the things to be looking for really are corroboration of what I think most scientists fundamentally believe, which is that C&P as a master regulator of bone growth is going to work across a wide variety of indications. And so, as we had seen with the hypochondroplasia program, it was actually sort of the first half of the cohort at the six-month mark that enabled FDA to gain confidence that we could go directly into phase three. And that's predicated on a lot of this biology, and therefore I think the important outcome of the ISS presentation at PES is going to be, are we seeing basically the same effect that we expect to see, you know, in the different types of statural disorders?

Speaker Change: Hi, This is <unk> and one for Robyn Uhm.

Robyn: Well I'm still goes I know you have spoken on competitors treatment for the consultation can you give us any color anecdotally about how patients I'll go global are prescribers think about <unk> is there room for both you could get through thank you.

Speaker Change: Yeah, we've shared robust and highly significant growth.

Robyn: <unk> data.

Robyn: From Vox I'll go in our clinical trials and as I just referenced the accumulating data on hiking is really quite positive and informative and you'll see more of that at a C. M. G. Demonstrating these longterm positive effects on growth importantly, also on improvements beyond height for exam.

Henry J. Fuchs: And as regards your second question, I think the prioritization process that's been described really boils down to fairly conventional metrics around time and cost to proof of concept or to global registration, value that gets created for patients and for shareholders with the idea that by setting a high bar for something like proof of concept, then you really only advance your winners. And by focusing on those, we hope that it will expedite development and bring faster and higher value to patients and shareholders of the undertaking. Thanks.

Robyn: Paul improvements in the physical domains of quality of life types of squares and so what we're really focused on his building our leadership position in the genetic sterile conditions, where we see an incredible potential for boxer, though again to normalize grows to sustain that normalization of growth through the entire growing period in half.

Robyn: The greatest possible impact and patience laws.

Robyn: Okay.

Speaker Change: Our next question comes from the line of <unk> <unk> with Wells Fargo. Please go ahead.

Wells Fargo: Great. Thank you very much for taking my question and congrats Alexander Malcolm maybe one question for you in General what is your general thoughts on.

Wells Fargo: Gene therapy, <unk> I'm, asking because a significant portion of your pipeline is investing in gene therapy, and we'd love to understand how you think about <unk> being January for rare diseases and what are the <unk>. Thank you.

Joseph P. Schwartz: Our next question comes from the line of Joseph Schwartz with Lee Rink Partners. Please go ahead. Great, thank you very much, and welcome, Alexander. I think I heard you say that the outcomes of the Strategic and Operating Review Committee could be communicated incrementally as well as at the investor day in the third quarter. So I was wondering if you have a sense of which updates might emerge sooner and which updates could require more time to form. Thanks, Joseph. Thanks very much for the question. The SORC is proceeding extremely well. We've met frequently, and we're making progress on the financial guidance, long-term financial guidance, and capital allocation strategy.

Speaker Change: Thank you very much your question.

Alexander Malcolm: So sorry, as I as I referenced a little bit, but let me get a little bit more detail you know we've got a very.

Alexander Malcolm: Broad and exciting.

Alexander Malcolm: Pipeline across both.

Alexander Malcolm: Mcdonald's is including gene therapy.

Alexander Malcolm: Gene therapy Sofa, obviously significant.

Alexander Malcolm: Potential benefits for patients transformative benefits.

Alexander Malcolm:

Alexander Malcolm: We have a and expertise and the ability.

Alexander Malcolm: To develop.

Alexander Malcolm: Matter of fact right.

Alexander Malcolm: Now commercialized.

Alexander Malcolm: Gene therapy multiple geographies I said that is a but as a unique set of capabilities that by marine highest as.

Alexander Hardy: We also have a lot of other work underway, as you get a sense from the cost optimization to acceleration of VoxOgo, even faster R&D prioritization, etc., etc. And right now, we're figuring out, you know, what is the best time to update the external world on our progress on these points. Obviously, the benefit of the investor day is that it allows us to put this all together in the strategic context of where we're going to take Biomarin into the future. At the same time, we're keen to share the information we can as soon as we can on the progress we're making. So, as I said in my prepared remarks, you know, please stand by for more information. The latest possible day will be investor day for all of this information.

Alexander Malcolm: As we look at all.

Alexander Malcolm: Which we look at all pipeline is.

Alexander Malcolm: It's as Hank was talking about you know, we're gonna be assessing Molly.

Alexander Malcolm: <unk> at a program by program basis, what is the transformative potential of the program together with the commercial potential at the same time. We're also looking at the overall strategy primary what are we really really good on where we confidence gonna have a sustainable competitive advantage card for it.

Alexander Malcolm: And that will include.

Alexander Malcolm: Asking and answering the question about you know our experience and exposure to gene therapy.

Alexander Malcolm: Which will then reform Sir the prioritization about portfolio so more to come on this please.

Speaker Change: What was your question, we'll have a clearer idea of this shared it it or invest today later at 2024.

Speaker Change: Alright, thank you.

Speaker Change: Our next question comes from the line of Gina Wang with Barclays. Please go ahead.

Alexander Hardy: If it makes sense, we'll communicate other information sooner. Thank you. Our next question comes from the line of Robyn Karnauskas with Tourist Securities. Please go ahead. Hi, this is Nishant. I'm on behalf of Robyn.

Gena Wang: Thank you I have two very quick questions. The first one is regarding Fox circle.

Gena Wang: And your press release, you say you're already treat it 2600 1300, please your patient across 41 active market.

Nishant: One on Logzogo. So I know you have spoken about competing oral treatments for achondroplasia. Can you give us any color anecdotally about how patients on Logzogo or prescribers think about the orals? Is there room for both if it gets approved? Thank you. You know, we've shared, you know, robust and highly significant growth data from VOX-EGO in our clinical trials. And as I just referenced, the accumulating data on height gain is really quite positive and informative. And you'll see more of that at ACMG, demonstrating these long-term positive effects on growth. Importantly, also on improvements beyond height. For example, improvements in the physical domains of quality of life.

Gena Wang: What is the total market <unk> patient numbers for these 41 active markets and also what is the pricing dynamics. There in a second very quickly regarding <unk> I think Alas earnings with <unk> <unk>.

Gena Wang: <unk> four Q23, Oh should we expect the remaining five patients to be does the infringe caught 824.

Gena Wang: Hi, Janet step here I'm Gonna take that first question on box ago patient numbers. So essentially that is for 41 markets represent kind of the core of the commercial footprint that we usually used to <unk>.

Jeffrey Robert Ajer: And so what we're really focused on is building our leadership position in genetic statural conditions, where we see an incredible potential for VOX-EGO, again, to normalize growth, to sustain that normalization of growth through the entire growing period, and to have the greatest possible impact on patients' lives. Thank you. Our next question comes from the line of Mohit Bansal with Wells Fargo. Please go ahead. Great, thank you very much for taking my question and congrats, Alexander, and welcome. Maybe one question for you, in general, what is your general thought on gene therapy as a therapeutic modality?

Janet: <unk> eligible patient numbers and market potential and for that group of patients that would know total about 20000 patients.

Gena Wang: Eligible and that's that's essentially matching so the lower age limit and the and the different labels, which are zero four months or six months, depending on where you are in the world.

Gena Wang: In terms of the <unk> Damien question back to Alexander.

Alexander: Thanks, Gina Yeah, Let me take your second question, we're gonna provide details on Q1.

Alexander: Including product revenues.

Alexander Hardy: I'm asking because a significant portion of your pipeline is investing in gene therapy and I would love to understand how you think about gene therapy in general for rare diseases and what are the puts and takes there. Thank you. Thank you very much for your question. Yes, as I as I referenced a little bit, but let me go in a little bit more detail. You know, we've got a very broad and exciting pipeline across multiple modalities, including gene therapy. Gene therapies obviously offer obviously significant potential benefits for patients, and transformative benefits. We have expertise and the ability to develop, manufacture, and now commercialize gene therapies in multiple geographies.

Alexander: At a conference call list in April.

Alexander:

Alexander: We're tracking progress on site readiness hemophilia treatment centers.

Alexander: Repairs.

Alexander: <unk> C Dx test positive C D X test.

Alexander:

Alexander: Clearly these metrics so far not yet correlated directly to patient uptight.

Speaker Change: So we're no longer going to be providing specific updates.

Alexander: On these on these metrics.

Alexander: Once again just to reiterate it we're gonna <unk> actual experience actual commercial Asian infusions format.

Alexander: Future expectations and will report.

Alexander: The end of the quarter about our progress this year with infusions revenue.

Speaker Change: Okay. Our next question comes from a line of Palm of teeth with Stifel. Please go ahead.

Alexander Hardy: I said, that is a unique set of capabilities that Biomarin has. As we look at our..., and as we look at our pipeline as... As Hank was talking about, we're going to be assessing on a program-by-program basis. What is the transformative potential?

Speaker Change: Hi, This is Julian on for Paul. Thanks, So much for taking our questions I guess just in terms of thinking about capital allocation moving forward, obviously, you're reviewing the pipeline could you. Please provide a little bit of color on you anticipate <unk>.

Julian: That's being in the pipeline, perhaps after cooling programs that don't meet them that high bar that you speak on for Advancement Uhm are you sort of more focusing on yoga on the commercial business for months ago. I guess, there's any color you can provide onto your account capital allocation for 2024 and beyond would be super helpful.

Alexander Hardy: of the program, together with the commercial potential. At the same time, we're also looking at the overall strategy, Biomarin. What are we really, really good at?

Speaker Change: Thank you.

Speaker Change: Yeah. Thanks for the question this is Brian.

Brian Mueller: We'll ask you to wait a bit longer for the outcomes of our strategic review to to give your details on our capital allocation strategy.

Alexander Hardy: Where are we confident we'll have a sustainable competitive advantage going forward? And that will include asking and answering the question about, you know, our exposure to gene therapy, which will then form POSAR, the prioritization of our portfolio. So more to come on this. Please, you know, hold your question.

Brian Mueller: I mean, we can say that you know internal innovation, given our track record and value created in the current business is gonna continue to be a priority, but we also recognize that <unk> not only carries a substantial amount of total cash and investments today, but we are now cash flow positive. So we are.

Alexander Hardy: We'll have a clearer idea of this, and we'll share it at our investor day later in 2020. Thank you. Our next question comes from Liana. Gena Wang with Barclays.

Gena Wang: Please go ahead. Thank you. I have two very quick questions.

Brian Mueller: Are committed to developing a capital allocation strategy, that's in the interest of maximizing shareholder value.

Jeffrey Robert Ajer: The first one is regarding VOXOGO. I think in your press release you say you have already treated 2,613 achondroplasia patients across 41 active markets. What is the total market opportunity in terms of achondroplasia patient numbers for these 41 active markets and also what is the pricing dynamics there? And the second question is very quickly regarding Loctavian.

Brian Mueller: That work is in process and we'll look forward very much to sharing sharing it with you, but we'll just ask you to stay tuned until we finish the work.

Brian Mueller: Thanks.

Brian Mueller: Our next question comes from the line the victim Berhow with Morgan Stanley. Please go ahead.

Berhow: Hi, Good afternoon. Thanks for taking my question, we had a follow up question on <unk> on a bit of a broader one. So you released mentions and you also just mentioned a couple of different areas of work that you're going through to help progressed commercialization here from.

Alexander Hardy: I think the last earnings report mentioned that six patients were ready to be dosed in for Q23. Should we expect the remaining five patients to be dosed in the first quarter of 24? Hi Gina, it's Jeff here.

Berhow: Patient education to cite readiness, but I was wondering now that you've had a few months of experience with the process for a Octavian what do you see as the one or two specific factors are drivers of uptake that you think.

Jeffrey Robert Ajer: I'm going to take that first question on Boxogo patient numbers. So, essentially, those 41 markets represent kind of the core of the commercial footprint that we usually use to quote eligible patient numbers and market potential. And for that group of patients, that would now total about 20,000 patients eligible, and that's essentially matching the lower age limit in the different labels, which are zero, four months, or six months, depending on where you are in the world. And in terms of the Roktavian question, back to Alexander.

Berhow: You know you have the most near term leverage with and control over that could support the trajectory here in 2024.

Brian Mueller: This is Jeff here, I'll I'll talk a little bit about that.

Jeff: What we've said is that we've seen bear.

Jeff: Very nice signals patient demand for example in the United States much of last year, we talked about the build up of a patient funnel in in the strategic market and priority market of Germany.

Alexander Hardy: Thanks, Gina. Yeah, let me take your second question. We're going to provide details on Q1, including product revenues, at our conference call in April. You know, we're tracking progress on site readiness at hemophilia treatment centers with payers, completed CDX tests, and positive CDX tests. But, you know, clearly, these metrics so far have not yet correlated directly to patient uptake.

Jeff: Where we had gotten good uptake of C. D X testing, we've also talked about the importance of sight readiness and having uhm reimbursement approvals that kind of clear that important reimbursement gate is Alexander noted, we haven't seen a direct correlation.

Jeff: So we haven't been able to say a this this or that or or these leading indicators.

Paul Matteis: So we're no longer gonna be providing specific updates on these metrics. Once again, just to reiterate it, we're gonna let the actual experience with actual commercial patient infusions inform our future expectations, and we'll report at the end of the quarter about our progress this year with infusions and revenue. Our next question comes from a line by Paul Matisse with Stiefel. Please go ahead, and this is Julian on. That's just

Jeff:

Jeff: Are are good predictive indicators of patient infusion in revenue upticks and so I think the idea from here is it instead of trying to better tune that model. We're gonna let the revenue the actual revenue do the speaking for <unk>.

Jeff: Our next question comes from the line of Tim Lugo was William Blair. Please go ahead.

Tim Lugo: Hi, Thanks for the questions you introduce operating margin your guidance and you have a nice step up year over year. What are the initial impressions on whether biomarin will be able to continue to expand operating margins.

Brian Mueller: Talking about capital allocation moving forward, obviously, you're reviewing the pipeline, but can you just provide a little bit of color on, you know, do you anticipate reinvesting in the pipeline perhaps www.larryweaver.com or are you sort of more focusing on growing the commercial business for VoxOgo? I guess just any color you can provide on future capital allocation. This is Brian.

Tim Lugo: Eventually reached north of 40 per cent like some of the other rare disease focused companies.

Speaker Change: Yeah. Thanks, Thanks, a lot I appreciate the question that's a great one so again we.

Speaker Change: We are pleased to be able to report and deliver over the last few years kind of year on year operating margin improvement we've been talking about it for awhile and it is we're pleased to be able to actually.

Brian Mueller: We'll ask you to wait a bit longer for the outcomes of our strategic review to give you details on our capital allocation strategy. But I can say that, you know, internal innovation, given our track record and value created in the current business, is going to continue to be a priority. But we also recognize that Biomarin not only carries a substantial amount of total cash investments today, but we are now cash flow positive.

Speaker Change: Deliver upon that.

Speaker Change:

Speaker Change: I'll give it to part answered your question you know on one hand.

Speaker Change: We know there's a lot of opportunity with the type of revenue growth that bomber and has not to mention the outcomes of the strategic work.

Speaker Change: We've talked about a lot today and its potential impact on revenue into the future.

Speaker Change: We also recognize that we've got operating model and cost efficiency opportunities.

Vikram Perho: So we are committed to developing a capital allocation strategy that's in the interest of maximizing shareholder value. That work is in process, and we will look forward very much to sharing it with you. But we'll just ask you to stay tuned until we finish the work. Thanks. Our next question comes from the line of Vikram Perho with Morgan Stanley. Please go ahead.

Speaker Change:

Speaker Change: We built this global infrastructure that now we're leveraging to support the strong launch of box they'll go for example, in a very deliberate and organic way over the years. We've reached a lotta scale, we've got world class capabilities across manufacturing R&D commercial business support.

Speaker Change: But we've been focused on growing and scaling for years and what that means is now we have a real opportunity to optimize and optimize the business model and make the cost structure more efficient. That's the work we're doing together with the S. A R C and by the way the entire leadership team in enterprise. These are enterprise wide.

Jeffrey Robert Ajer: Thanks for taking our question. We had a follow-up question on Roktavian, a bit of a broader one. So your release mentions, and you also just mentioned, a couple of different areas of work that you're going through to help progress commercialization here, from Patient Education to Site Readiness, but I was wondering, now that you've had a few months of experience with the process for Roctavian, what do you see as the one or two specific factors or drivers of uptake that you think you have the most near-term leverage with and control over that Hi there, Grim.

Speaker Change: Is that the the the companies really rallying behind and the second part is my question is for that reason you will have to ask you to stay tuned but by all means you can picture of the work that we're doing to design, what the appropriate and deliverable financial targets the longterm guidance purposes.

Speaker Change: Will be for the company and and we'll be sure to not just share those numerically, but the rationale the strategy and our plans to deliver upon them. So that's just gonna take a bit more time. Thank.

Jeffrey Robert Ajer: This is Jeff here. I'll talk a little bit about that. What we've said is that we've seen very nice signals of patient demand. For example, in the United States, we talked about the buildup of a patient funnel in the strategic market and priority market of Germany, where we had gotten good uptake of CDX testing. We've also talked about the importance of site readiness and having reimbursement approvals that kind of clear that important reimbursement gate. But, as Alexander noted, we haven't seen a direct correlation, so we haven't been able to say, hey, this or that or these leading indicators are good predictive indicators of patient infusion and revenue uptake. And so I think the idea from here is instead of trying to better tune that model, we're gonna let the revenue, the actual revenue, do the speaking for Rottweil. Our next question comes from a line from Tim Lugo with William Blair.

Speaker Change: Thank you, though for the credit.

Speaker Change: I understand thank you.

Speaker Change: Our next question comes from the line of Olivia Prayer was Cantor Fitzgerald. Please go ahead.

Olivia Prayer: Hey, good afternoon, guys. Thank you for the question wanted to ask about lifecycle management for your box of a franchise. Obviously you have a lot of expansion opportunities within that product.

Olivia Prayer: But could we see any efforts to maybe better optimize the dosing schedule or maybe any other avenues to to keep that product as competitive as possible. Thank you.

Speaker Change: Yeah. Thanks, that's a good question and yes. In fact, we do plan to undertake some further dose optimization right. Now are thinking is to try to do that in parallel with registration, enabling trials, but again details too.

Speaker Change: Be communicated wind study designs for final after a regulatory authority alignment.

Speaker Change: Our next question comes from the line of <unk> <unk> with BMO capital markets. Please go ahead.

Tim Lugo: Please go ahead. Thanks for the questions. You introduced operating margin in your guidance, and you have a nice step up year over year. What are the initial impressions on whether Biomarin will be able to continue to expand operating margins and eventually reach north of 40% like some of the other rare disease focus companies? Yeah, thanks.

Speaker Change: Hello, everyone. Congrats on the <unk>. Thanks for taking out a question given that your AD and D data plan for the third quarter of 2024, which is about a <unk> to call their and likely this is when you will put <unk> pipeline pirate. These dates in the case I'm wondering.

Brian Mueller: Thanks a lot, Tim. I appreciate the question. It's a great one.

Speaker Change: Whether you will continue to progress all pipeline programs full steam.

Brian Mueller: So again, we are pleased to be able to report and deliver, over the last few years, kind of year-on-year operating margin improvement. We've been talking about it for a while, and it is, we're pleased to be able to actually deliver on that. I'll give a two-part answer to your question.

Speaker Change: The state quoted or you are going to pause.

Speaker Change: Progression of some of the programs and data get decided on database. Thank you.

Speaker Change: <unk> you know the.

Speaker Change: A big part of the purpose of in the early part of the year a priority prioritizing you're already portfolio ties to the conversations that Brian was just having around capital allocation of Alexander was having around longer term financial outlook. I think about that is that you know it's a real it's a it's a great thing that are.

Brian Mueller: You know, on the one hand, we know there's a lot of opportunity with the type of revenue growth that Biomarin has, not to mention the outcomes of the strategic work that we've talked about a lot today and its potential impact on revenue into the future. We also recognize that we've got operating model and cost efficiency opportunities. We built this global infrastructure that we're now leveraging to support the strong launch of Boxogo, for example, in a very deliberate and organic way over the years. We've reached a lot of scale.

Speaker Change: Company can generate cash that can be reinvested in our R&D portfolio and we have to earn that through developing assets that have value to then reapply to generate new Madison. So we have to do that in a business context and so as soon as we can make decisions about what's gonna go for.

Brian Mueller: We've got world-class capabilities across manufacturing, R&D, commercial, and business support, but we've been focused on growing and scaling for years. And what that means is now we have a real opportunity to optimize and optimize the business model and make the cost structure more efficient. That's the work we're doing together with the SORC. And by the way, the entire leadership team in Enterprise, these are enterprise-wide initiatives that the company is really rallying behind. And the second part of my question is, for that reason, we'll have to ask you to stay tuned, but by all means, you can imagine the work that we're doing to design what the appropriate and deliverable financial targets for long-term guidance purposes will be for the company. And we'll be sure to not just share those numerically but the rationale, the strategy, and our plans to deliver upon them. So that's just going to take a bit more time. Thank you, though, for the question. I understood.

Speaker Change: <unk>, we want to invest in expediting that and also things that are not gonna go forward, we want to make sure that we.

Speaker Change: Don't spend money on things that are not gonna go forward. So that's very much the intention and it's I think ties to Alexander statement of how the the progress of of of our process through to Investor day, Uhm could be potentially incrementally informed over the course of the year.

Speaker Change: Our next question comes from a line of Jack Allen was bird. Please go ahead.

Jack Allen: Alright, Thanks for taking my question and congratulations all progress made over the course of the quarter I wanted to ask one on <unk> you mentioned that about 70 per cent of the new you best starts in the fourth quarter for the younger patients and illegal expansion I guess could you write some more contacts around how penetrated the older patients are and how should we think about growth of October so moving forward is it mainly <unk>.

Speaker Change: That will come from younger patients or is there some opportunity to expand I've taken the older patients in the U S as well.

Olivia Brayer: Thank you. Our next question comes from the line of Olivia Brayer with Cancer Fitzgerald. Please go ahead. Hey, good afternoon, guys.

Speaker Change: Hi, Thanks for the question Jack Uhm in the United States, we haven't disclosed penetration rates and and and we're not going to introduce that metric overall with reported numbers of about 2600.

Henry J. Fuchs: Thank you for the question. I wanted to ask about lifecycle management for your Voxogo franchise. Obviously, you have a lot of expansion opportunities within that product, but could we see any efforts to maybe better optimize the dosing schedule or maybe any other avenues to keep that product as competitive as possible? Thank you.

Speaker Change: <unk> and you heard me quote.

Speaker Change: Question to Gina earlier of an eligible patient population of 20000, you can do the quick arithmetic on that yourself <unk>, specifically from the United States, which is one of our largest and highest value markets were really encouraged by both the continued up.

Henry J. Fuchs: And yes, in fact, we do plan to undertake some further dose optimization. Right now, our thinking is to try to do that in parallel with registration-enabling trials. But again, details to be communicated when study designs are final, after regulatory authority aligns. Our next question comes from the line of Kostas Biliris with BMO Capital Markets. Please go ahead. Hello, everyone.

Speaker Change: Taken the older children, those ages five and up from the original approval and also the the new demand from the the younger patients. So I think we're pretty confident that we've got an opportunity for for increased uptake they're going forward.

Kostas Biliris: Congratulations on the progress. Thanks for taking our question. Given that your R&D day is planned for the third quarter of 2024, which is about a year after Alex took over, and likely this is when you will potentially share pipeline prioritization details, I'm wondering whether you will continue to progress all pipeline programs full steam until this third quarter, or are you going to pause the progression of some of the programs until you decide on their fate?

Speaker Change: Great. Thanks.

Speaker Change: Our next question comes from the line of David Leibowitz with Citigroup. Please go ahead.

David N. Lebowitz: Alright. Thank you very much for taking my question I'm just following up on that what's the 70 per cent of patients.

David N. Lebowitz: <unk> 70 scripts being young patients.

David N. Lebowitz: Is it <unk>.

David N. Lebowitz: To assume that number would be maintained next year or should that dialed back as the year goes on.

Henry J. Fuchs: Thank you. I think a big part of the purpose in the early part of the year of prioritizing the R&D portfolio ties to the conversations that Brian was just having around capital allocation and that Alexander was having around the longer-term financial outlook. What I think about that is that it's a great thing that our company can generate cash that can be reinvested in our R&D portfolio, and we have to earn that through developing assets that have value to then reapply to generate new medicines. We have to do that in a business context. As soon as we can make decisions about what's going to go forward, we want to invest in expediting that, and also things that are not going to go forward; we want to make sure that we don't spend money on things that are not going to go forward. That's very much the intention, and it ties to Alexander's statement of how the progress of our process through to investor day could potentially be potentially incrementally informed over the course of the year. Our next question comes from a line by Jack Allen with Baird.

Speaker Change: Hi, David <unk>, let me take that went on I I don't think we have enough data to specifically say that we're gonna maintain that that mix, but it's that's a one time metric intended to give you a little bit of color on how things are going in.

Geoff Meacham: That key markets since we got the younger H label expansion.

Speaker Change: But it's it's an important signal and I think it's it's a good win goulden encouraging looking forward.

Jack Allen: Thanks for taking my question.

Speaker Change: Our final question comes from a line of Luka E C with R. B C capital markets. Please go ahead.

Jack Allen: Oh, great. Thanks, so much thanks for choosing in and maybe.

Jack Allen: Maybe Alexander a D R and D D last year, which I. Appreciate it was before your time <unk> quite extensively about lifecycle management. Some <unk> tests, you getting patients to neutralizing antibodies to 85.

Speaker Change: Patience with the factor Ace inhibitors younger patients and so on give us a relatively slow launch is that still the plan or is there a scenario, which don't invest that capital and just <unk> you prioritize operational efficiency to really make the story here are driven primarily by <unk>, alright, ma'am rocks and called their much appreciate it. Thanks so much.

Jack Allen: Please go ahead. Great, thanks for taking our question and congratulations on all the progress made over the course of the quarter. I wanted to ask one on VoxOgo.

Jeffrey Robert Ajer: You mentioned that about 70% of the new U.S. starts in the fourth quarter were from younger patients in the label expansion. Could you provide some more context around how penetrated the older patients are, and how should we think about growth of VoxOgo moving forward? Is it mainly expected that it will come from younger patients, or is there still opportunity to expand uptake in older patients in the U.S. as well? Thanks for the question, Jack. In the United States, we haven't disclosed penetration rates, and we're not going to introduce that metric.

Speaker Change: We do intend to include a review of those studies in our portfolio assessment of prioritization.

Speaker Change: And so we will communicate the plans for each of the additional potential <unk> indications that we did outline at R&D day that you did just list and.

Speaker Change: As we complete our a portfolio prioritization process as well as our overall corporate strategy Uhm and so will follow up then.

Speaker Change: And I would just add to that that as we said without R&D prioritization is looking at the potential.

Speaker Change: Benefit in terms of the.

Jeffrey Robert Ajer: Overall, with reported numbers of about 2,600 patients, and you heard me quote the question to Gina earlier of an eligible patient population of 20,000, you can do the quick arithmetic on that yourself. Specifically, in the United States, which is one of our largest and highest-valued markets, we're really encouraged by both the continued uptake in older children, those ages five and up, from the original approval, and also the new demand from younger patients. So I think we're pretty confident that we've got an opportunity for increased uptake there going forward. Great, thanks. Our next question comes from David Lebowitz with Citigroup. Please go ahead. Thank you very much for taking my question. Just following up on that, what are 70% of patients on Voxogo of Newscripts being young patients? Is it us or not?

Speaker Change: The medical impact together with the commercial potential so it will be taken to mind, our experience with the commercial uptake.

Jeffrey Robert Ajer: Rotated.

Hank Fuchs: To inform.

Speaker Change: The business case around there's lifecycle.

David N. Lebowitz: Thank you very much.

Jeffrey Robert Ajer: I wouldn't doubt I'd like to turn the call over to Alexander Hardy, President and C. E O of bio marine for closing remarks.

David N. Lebowitz: Thank you very much for joining us today as you've heard we are really hot at work here on shaping the future corporate no D. R. A strawberry shake.

David N. Lebowitz: As well as setting ambitious longterm financial goals as you've heard these are on about accelerating revenue and also profitability.

Alexander Hardy: We're approaching this this work with a sense of urgency and we're making significant progress looking forward to sharing that with you on a timely basis.

Jeffrey Robert Ajer: So.

David N. Lebowitz: assume that that number would be maintained next year, or should that be lowered as the year goes on? Hi David. Let me take that one on. I don't think we have enough data to specifically say that we're going to maintain that mix, but that's a one-time metric intended to give you a little bit of color on how things are going in that key market since we got the younger age label expansion. But it's an important signal, and I think it's a good one, good and encouraging. I'm looking forward to it. Thanks for taking my question. Our final question comes from the line of Luca E.C. with RBC Capital Markets.

David N. Lebowitz: <unk>. Please stay tuned for additional updates. Thank you very much for your attention and your questions and goodbye.

Speaker Change: This concludes today's call you may now disconnect.

David N. Lebowitz: [music].

Luca E.C.: Please go ahead. Oh, great. Thanks so much. Thanks for squeezing in. Maybe, Alexander, at the R&D day last year, which I appreciate was before your time, Biomarin talked quite extensively about lifecycle management for Vialrox, including testing patients and neutralizing antibodies to AAV5, patients with factor VIII inhibitors, younger patients, and so on. Given the relatively slow launch, is that still the plan? Or is there a scenario where you just don't invest that capital; you just prioritize operational efficiency?

Alexander Hardy: To really make this story here driven primarily by Voxelgo rather than Vialrox. Any call there will be much appreciated. Thanks so much. We do intend to include a review of those studies in our portfolio assessment and prioritization, and so we'll communicate the plans for each of the additional potential Roctavian indications that we did outline at R&D Day that you just listed, and you know as we complete our portfolio prioritization process as well as our overall corporate strategy, and we'll follow up then. And I would just add to that that, as we've said, R&D prioritization is looking at the potential benefit in terms of the medical impact together with the commercial potential. So we'll be keeping that in mind. Our experience with the commercial uptake of Roktavien will inform, you know, the business case around those life-cycle developments.

Alexander Hardy: Thank you very much. I would now like to turn the call over to Alexander Hardy, President and CEO of Biomarin, for closing remarks. Thank you very much for joining us today. As you've heard, we are really hard at work here shaping the future corporate and R&D strategy, as well as setting ambitious long-term financial goals. As you've heard, these are about accelerating revenue and also profitability. We're approaching this work with a sense of urgency, and we're making significant progress. We're looking forward to sharing that with you on a timely basis. So, as you heard, please stay tuned for additional updates. Thank you very much for your attention and your questions. This concludes today's call. You may now disconnect.