BioMarin Pharmaceutical Inc (BMRN) 2025 Q1 法說會逐字稿

Good day, everyone, and welcome to the BioMarin Pharmaceutical first-quarter 2025 conference call. Just a reminder that this conference is being recorded. I would now like to hand things over to Ms. Traci McCarty. Please go ahead, ma'am.

大家好，歡迎參加 BioMarin Pharmaceutical 2025 年第一季電話會議。只是提醒一下，這次會議正在錄製。現在我想把事情交給 Traci McCarty 女士。請繼續，女士。

Thank you, operator. To remind you, this nonconfidential presentation contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including expectations regarding BioMarin's financial performance, commercial products and potential future products in different areas of therapeutic research and development. Results may differ materially depending on the progress of BioMarin's product programs, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market and developments by competitors, and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, such as 10-Q, 10-K and 8-K reports.

謝謝您，接線生。提醒您，本非機密簡報包含有關 BioMarin Pharmaceutical Inc. 業務前景的前瞻性陳述，包括對 BioMarin 的財務業績、商業產品以及不同治療研究和開發領域的潛在未來產品的預期。由於 BioMarin 產品項目的進展、監管機構的行動、資本的可用性、醫藥市場的未來行動和競爭對手的發展，以及 BioMarin 向美國證券交易委員會提交的文件（如 10-Q、10-K 和 8-K 報告）中詳細說明的因素，結果可能會有顯著差異。

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

此外，我們將在今天的電話會議中使用 G 條例中定義的非 GAAP 財務指標。這些非公認會計準則 (non-GAAP) 指標不應被視為與按照美國公認會計準則 (US GAAP) 編制的財務指標分離的替代指標或優於這些指標，您可以在收益新聞稿和收益報告中找到與美國公認會計準則 (US GAAP) 相關的對賬，這兩者都可以在我們網站的投資者關係部分找到。請注意，除非另有說明，我們對今天電話會議的評論將集中於非公認會計準則財務指標。

On the call from BioMarin management today are Alexander Hardy, President and Chief Executive Officer; Brian Mueller, Executive Vice President, Chief Financial Officer; Cristin Hubbard, Executive Vice President, Chief Commercial Officer; and Greg Friberg, Executive Vice President, Chief R&D Officer. I will now turn the call over to BioMarin's President and CEO, Alexander Hardy.

今天參加 BioMarin 管理層電話會議的有總裁兼執行長 Alexander Hardy、執行副總裁兼財務長 Brian Mueller、執行副總裁兼首席商務長 Cristin Hubbard 和執行副總裁兼首席研發長 Greg Friberg。現在我將把電話轉給 BioMarin 總裁兼執行長亞歷山大哈迪 (Alexander Hardy)。

Thank you, Traci, and good afternoon, everyone. Thank you for joining us today for our first quarter 2025 results update. We are pleased to have delivered strong financial performance and revenue growth of 15% in the quarter. On the bottom line, non-GAAP earnings per share of $1.13 represented a 59% year-over-year increase, reflecting significant profitability expansion, nearly 4x the rate of top line growth. This performance highlights the fundamental value of our transformative medicines and the strength of our business, both of which are key attributes that distinguish BioMarin.

謝謝你，特蕾西，大家下午好。感謝您今天參加我們的 2025 年第一季業績更新。我們很高興本季取得了強勁的財務業績和 15% 的營收成長。總體而言，非公認會計準則每股收益為 1.13 美元，年成長 59%，反映出獲利能力顯著擴張，幾乎是營業額成長率的 4 倍。這項業績凸顯了我們變革性藥物的根本價值和業務實力，這兩者都是 BioMarin 與眾不同的關鍵屬性。

These results pave the way for record full year performance in 2025 and boost cash generation for reinvestment in innovation and expansion. Last September, we announced changes to BioMarin's strategy and operating model. Since that time, we have been focused on implementing these changes while at the same time, delivering strong growth and profitability. Looking ahead, we expect to see the continued implementation and benefits of this transformation deliver even stronger results and innovation in the coming quarters and beyond.

這些結果為 2025 年創紀錄的全年業績鋪平了道路，並促進了現金流的產生，用於創新和擴張的再投資。去年九月，我們宣布了 BioMarin 策略和營運模式的變更。自那時起，我們一直專注於實施這些變革，同時實現強勁的成長和獲利。展望未來，我們期望看到這項轉型的持續實施和效益在未來幾季及以後帶來更強勁的成果和創新。

Turning briefly to external dynamics impacting the sector, we believe BioMarin is well positioned to manage through uncertainty across a number of areas. As the preeminent innovator of medicines that treat rare conditions, BioMarin is less exposed to macroeconomic conditions impacting other sectors. Because so many of our medicines are treatments for children, we have limited exposure to policies impacting Medicare, which covers roughly only 2% of our US patient population.

簡要談談影響該行業的外部動態，我們認為 BioMarin 已做好準備應對多個領域的不確定性。作為治療罕見疾病藥物的傑出創新者，BioMarin 較少受到影響其他行業的宏觀經濟條件的影響。由於我們的許多藥物都是針對兒童的，因此我們受到影響醫療保險政策的影響有限，醫療保險僅涵蓋我們美國患者群體的約 2%。

In addition, BioMarin's core fundamentals also provide a level of insulation from external unknowns. Increasing cash generation, our extensive global revenue base with approximately 2/3 of our total revenues originating from outside United States, along with our established global commercial, regulatory and manufacturing capabilities position us well in an evolving and dynamic market environment.

此外，BioMarin 的核心基本面也在一定程度上抵禦了外部未知因素的影響。現金產生能力不斷提高，我們擁有廣泛的全球收入基礎，其中約有三分之二的總收入來自美國以外，再加上我們成熟的全球商業、監管和製造能力，使我們在不斷發展和活躍的市場環境中佔據有利地位。

Moving to the specific uncertainties around potential pharmaceutical tariffs. We are analyzing potential exposure and mitigation tactics under multiple scenarios. As BioMarin's medicines address relatively small patient populations around the world, we manufacture products that address these rare indications in single locations, either in the US or Europe.

轉向有關潛在藥品關稅的具體不確定性。我們正在分析多種情況下的潛在暴露和緩解策略。由於 BioMarin 的藥物針對的是全球相對較少的患者群體，因此我們在美國或歐洲的單一地點生產針對這些罕見適應症的產品。

Based on our current understanding, we believe that the global scope of our business model, with approximately 2/3 of total revenues generated from outside of the United States and a significant level of US-based manufacturing will provide some protection from potential tariff impacts should innovative medicines for rare conditions be targeted. Important to note, BioMarin has immaterial exposure to US tariffs for China, Mexico and Canada across its global supply chain operations and product sales.

根據我們目前的理解，我們認為，我們的商業模式具有全球範圍，其中約 2/3 的總收入來自美國以外，且很大一部分製造業務在美國進行，如果針對的是罕見疾病的創新藥物，那麼這種模式將在一定程度上避免潛在的關稅影響。值得注意的是，BioMarin 在其全球供應鏈營運和產品銷售中，對美國對中國、墨西哥和加拿大徵收的關稅影響不大。

Turning now to potential new products and expansions. We're making good progress on our innovation strategy. I am pleased to share that we recently completed enrollment in our pivotal Phase III study with VOXZOGO in children with hypochondroplasia, paving the way for a potential launch in 2027. With PALYNZIQ, based on the positive pivotal data we announced in April, we are on track to submit applications in the second half of this year in the United States and Europe for the treatment of adolescents. In addition, we expect to share early clinical results later this year from both BMN 351 for Duchenne muscular dystrophy and BMN 333, a long-acting CNP, two candidates that may provide highly differentiated treatment options to the conditions they target.

現在來談談潛在的新產品和擴展。我們的創新策略正在取得良好進展。我很高興地告訴大家，我們最近完成了 VOXZOGO 針對軟骨發育不全兒童的關鍵性 III 期研究的招募，為 2027 年的潛在上市鋪平了道路。對於PALYNZIQ，基於我們4月份公佈的積極關鍵數據，我們預計在今年下半年在美國和歐洲提交用於治療青少年的申請。此外，我們預計將在今年稍後分享用於治療杜氏肌肉營養不良症的 BMN 351 和長效 CNP 的 BMN 333 的早期臨床結果，這兩種候選藥物可能針對其目標疾病提供高度差異化的治療選擇。

Finally, we expect to fortify our internal innovation with business development, as we feel that BioMarin's established global capabilities, coupled with the external environment, create opportunities that will support our growth agenda.

最後，我們希望透過業務發展來加強我們的內部創新，因為我們認為 BioMarin 成熟的全球能力加上外部環境將創造機會，以支持我們的成長議程。

In summary, we believe we are well positioned to manage through ongoing market uncertainty based on the global demand for our innovative medicines. Through BioMarin's strategic transformation implemented over the last year, we have set ourselves up to deliver significant value creation for all our stakeholders in 2025 and beyond. Thank you for your attention. I will now turn the call over to Brian to provide our financial highlights for the quarter.

總之，我們相信，基於全球對我們創新藥物的需求，我們有能力應對持續的市場不確定性。透過去年實施的 BioMarin 策略轉型，我們已準備好在 2025 年及以後為所有利害關係人創造重大價值。感謝您的關注。現在我將把電話轉給 Brian，讓他提供本季的財務亮點。

Thank you, Alexander. Please refer to today's press release for detailed first quarter 2025 results, including reconciliations of GAAP to non-GAAP financial measures. All 2025 results will be available in our upcoming Form 10-Q, which we expect to file in the coming days.

謝謝你，亞歷山大。請參閱今天的新聞稿，以了解 2025 年第一季的詳細業績，包括 GAAP 與非 GAAP 財務指標的對帳。所有 2025 年的結果將在我們即將發布的 10-Q 表中公佈，我們預計將在未來幾天內提交該表格。

We are pleased with BioMarin's strong results across the business in the first quarter of 2025. First quarter 2025 total revenues rose 15% to $745 million compared to the same period last year. VOXZOGO's demand fueled growth, with global revenue reaching $214 million, a 40% increase year-over-year and continuing its strong growth trajectory since approval 4 years ago. Revenue from the enzyme therapies business unit grew 8% year-over-year to $484 million, with substantial contributions from PALYNZIQ, which grew 22% compared to the first quarter of 2024.

我們對 BioMarin 在 2025 年第一季整個業務的強勁業績感到滿意。2025 年第一季總營收與去年同期相比成長 15%，達到 7.45 億美元。VOXZOGO 的需求推動了成長，全球營收達到 2.14 億美元，年增 40%，延續了 4 年前獲準以來的強勁成長軌跡。酵素療法業務部門的營收年增 8% 至 4.84 億美元，其中 PALYNZIQ 做出了巨大貢獻，與 2024 年第一季相比成長了 22%。

As I mentioned in February, we expect total revenues to be higher in the second half of this year compared to the first half due to anticipated order timing dynamics across the portfolio. These dynamics apply to VOXZOGO as well, with the product now available in 49 countries. While a significant volume of new patients have started VOXZOGO therapy in recent quarters through today, we note that quarterly VOXZOGO revenues looking back to Q4 2024 and anticipated trends through Q2 2025 have revenues slightly disconnected from patient growth and appearing relatively similar quarter-to-quarter. Importantly, we continue to expect VOXZOGO full year revenues to be between $900 million and $950 million, which at the midpoint represents 26% full year growth.

正如我在二月提到的，由於預期整個投資組合的訂單時間動態，我們預計今年下半年的總收入將高於上半年。這些動態也適用於 VOXZOGO，目前已在 49 個國家/地區銷售。雖然最近幾季已有大量新患者開始接受 VOXZOGO 治療，但我們注意到，回顧 2024 年第四季的 VOXZOGO 季度收入以及預計到 2025 年第二季度的趨勢，其收入與患者增長略有脫節，並且季度間表現相對相似。重要的是，我們繼續預期 VOXZOGO 全年營收將在 9 億美元至 9.5 億美元之間，中間值代表全年成長 26%。

Moving to expenses. In the first quarter of 2025, non-GAAP R&D expense was $147 million and lower than the same quarter in 2024. Operating trends in the first quarter of this year were consistent with those in the fourth quarter of last year, reflecting the impact of BioMarin's R&D reprioritization. Looking ahead in 2025, we plan to increase R&D spend on our pipeline priorities and the VOXZOGO new indication.

轉向開支。2025 年第一季度，非 GAAP 研發費用為 1.47 億美元，低於 2024 年同期。今年第一季的營運趨勢與去年第四季一致，反映了 BioMarin 重新調整研發重點的影響。展望 2025 年，我們計劃增加對管道重點和 VOXZOGO 新適應症的研發支出。

In the first quarter, non-GAAP SG&A expense of $183 million decreased year-over-year, also due to the impact of cost transformation initiative, including reduced activities related to the company's focused ROCTAVIAN strategy announced last year, while we observed reduced expenses due to these dynamics in the quarter, and noting that Q1 is typically a lower spend quarter for BioMarin. Throughout the remainder of 2025, we expect SG&A expense to increase as we invest in the strategic priorities of the newly formed skeletal conditions and enzyme therapies business units.

第一季度，非公認會計準則銷售、一般及行政費用為 1.83 億美元，同比下降，這也是由於成本轉型計劃的影響，包括與公司去年宣布的重點 ROCTAVIAN 戰略相關的活動減少，同時我們觀察到由於本季度的這些動態而導致的費用減少，並註意到第一季通常是 BioMarin 支出較低的季度。在 2025 年剩餘時間內，隨著我們對新成立的骨骼疾病和酵素療法業務部門的策略重點進行投資，我們預計銷售、一般及行政費用 (SG&A) 支出將會增加。

Moving to profitability. Non-GAAP operating margin reached 35.7% for the first quarter of 2025, an expansion of 11.9 percentage points year-over-year. These results were driven by strong revenue performance and a spending reset as we prepare to invest more aggressively across R&D and SG&A in the coming quarters. For R&D, this will include global applications for PALYNZIQ adolescent approval, expansion of our BMN 351 and BMN 333 studies, as well as our clinical programs advancing multiple new indications with VOXZOGO, just to name a few.

轉向盈利。2025年第一季非公認會計準則營業利益率達35.7%，較去年同期成長11.9個百分點。這些結果是由強勁的收入表現和支出重置所推動的，因為我們準備在未來幾季在研發和銷售、一般及行政費用方面進行更積極的投資。對於研發，這將包括 PALYNZIQ 青少年批准的全球申請、我們的 BMN 351 和 BMN 333 研究的擴展，以及我們利用 VOXZOGO 推進多種新適應症的臨床項目，僅舉幾例。

For SG&A, this will include investments in VOXZOGO and enzyme therapy global commercial expansion activities and commercial launch preparations for hypochondroplasia and PALYNZIQ and adolescents. Over the coming quarters, increased spending on R&D and SG&A is expected to result in slightly lower non-GAAP operating margin in Q2 through Q4 2025. However, we expect that quarterly non-GAAP operating margins will balance out over the course of the year to our full year non-GAAP operating margin guidance of between 32% to 33% that we reaffirmed today. Strong non-GAAP operating margin flowed through to the bottom line, resulting in first quarter non-GAAP diluted earnings per share of $1.13, an increase of 59% year-over-year. Consistent with prior quarters, non-GAAP diluted earnings per share grew at a rate higher than revenue growth, reflecting BioMarin's focus on operational efficiency and our value commitment to shareholders.

對於銷售、一般及行政費用 (SG&A)，這將包括對 VOXZOGO 和酶療法全球商業擴展活動的投資以及針對軟骨發育不全和 PALYNZIQ 和青少年的商業發布準備。未來幾季，研發和銷售、一般及行政費用的增加預計將導致 2025 年第二季至第四季的非 GAAP 營業利潤率略有下降。不過，我們預期季度非公認會計準則營業利潤率將在全年內達到我們今天重申的全年非公認會計準則營業利潤率指引值 32% 至 33% 之間。強勁的非公認會計準則營業利潤率轉化為利潤，導致第一季非公認會計準則每股攤薄收益為 1.13 美元，較去年同期成長 59%。與前幾季一致，非 GAAP 稀釋每股盈餘的成長率高於收入成長率，反映了 BioMarin 對營運效率的關注以及我們對股東的價值承諾。

Following my comments on the timing of both revenue and expenses in 2025, non-GAAP earnings per share is not expected to be a smooth progression from quarter-to-quarter. As implied with the strong Q1 results and our reaffirmed 2025 non-GAAP earnings per share guidance, earnings per share could decrease in certain quarters compared to this first quarter, but accumulate to the expected double-digit growth for the full year. Please note that while this reiteration of guidance reflects the impact of the currently enacted US. tariffs, it does not reflect the impact of potential future pharmaceutical tariffs.

根據我對 2025 年收入和支出時間的評論，預計非 GAAP 每股收益不會逐季度平穩增長。正如強勁的第一季業績和我們重申的 2025 年非公認會計準則每股收益指引所暗示的那樣，與今年第一季相比，某些季度的每股收益可能會下降，但全年將累計達到預期的兩位數增長。請注意，雖然此重申指引反映了當前美國實施的關稅的影響，但並未反映未來潛在藥品關稅的影響。

BioMarin's increasing profitability continues to generate cash, with $174 million of positive operating cash flow in the first quarter of 2025, a 271% increase over Q1 2024. This trend is expected to continue and provides the opportunity to execute on our top capital allocation priority of investing in innovation and future growth to positively impact our patients, employees and shareholders.

BioMarin 不斷成長的獲利能力持續產生現金，2025 年第一季的正營運現金流為 1.74 億美元，比 2024 年第一季成長 271%。預計這一趨勢將持續下去，並為我們的首要資本配置重點提供機會，即投資於創新和未來成長，從而對我們的患者、員工和股東產生積極影響。

In conclusion, we are pleased to begin 2025 with another strong financial performance. It gives us confidence that BioMarin will continue to execute on all of the elements of our revitalized strategy. I will now hand the call over to Cristin, who will speak to our commercial performance. Cristin?

總而言之，我們很高興在 2025 年迎來另一次強勁的財務表現。這讓我們有信心，BioMarin 將繼續執行我們振興策略的所有要素。現在我將把電話交給克里斯汀，她將介紹我們的商業表現。克里斯汀？

Thank you, Brian. The team's focus on commercial execution led to another quarter of strong growth across the business. Starting with VOXZOGO for the treatment of achondroplasia, we were very pleased to have delivered 40% year-over-year revenue growth, with strong contributions from across the globe. As of the end of the first quarter, children across 49 countries had access to VOXZOGO treatment, and we are making strong progress toward our goal of opening access in more than 60 countries by 2027.

謝謝你，布萊恩。該團隊對商業執行的關注推動整個業務又一個季度的強勁增長。從用於治療軟骨發育不全的 VOXZOGO 開始，我們非常高興地實現了 40% 的同比增長，這得益於來自全球各地的強勁貢獻。截至第一季末，已有 49 個國家的兒童接受了 VOXZOGO 治療，我們正在朝著 2027 年前在 60 多個國家開放治療的目標邁進。

In the United States, we are focused on implementing initiatives targeting new patient uptake, which we expect will drive continued expansion beginning in the second half of the year. Commercialization efforts include increasing field personnel to broaden the prescriber base and implementing activities to further drive the adoption of VOXZOGO treatment. Outside of the US, we saw continued strength across all markets. Taken together, we expect these US and OUS dynamics to result in higher VOXZOGO revenue in the second half of 2025 compared to the first half of 2025.

在美國，我們專注於實施針對新患者的舉措，我們預計這將推動從今年下半年開始的持續擴張。商業化努力包括增加現場人員以擴大處方者基礎，並實施活動以進一步推動 VOXZOGO 治療的採用。除美國以外，我們看到所有市場持續走強。綜合起來，我們預計這些美國和澳洲的動態將導致 2025 年下半年 VOXZOGO 的收入比 2025 年上半年更高。

As our global presence treating achondroplasia expands with strong momentum contributed from recently published international guidelines which recommend diagnosis and early treatment with VOXZOGO, we are well positioned to enter the hypochondroplasia market in 2027, pending support of Phase III data next year. We are focusing on our global launch preparations, and we'll keep you apprised as progress unfolds.

隨著我們在全球治療軟骨發育不全症領域的業務不斷擴大，以及最近發布的國際指南（建議使用 VOXZOGO 進行診斷和早期治療）的強勁勢頭，我們已準備好在 2027 年進入軟骨發育不全症市場，但需等待明年第三階段數據的支持。我們正專注於全球發布的準備工作，並將隨時向您通報進度。

Moving to our enzyme therapies. We are pleased with this business unit's performance in the first quarter, where total enzyme therapy revenues increased 8% year-over-year. Starting with specific dynamics in the quarter, we saw continued strong growth with PALYNZIQ increasing 22% and ALDURAZYME up 40% year-over-year. VIMIZIM, our second largest revenue contributor, was uneven compared to the prior quarter, typical of ordering dynamics with our mature global brands.

轉向我們的酵素療法。我們對該業務部門第一季的表現感到滿意，酵素療法總收入比去年同期成長了 8%。從本季的具體動態開始，我們看到持續強勁成長，其中PALYNZIQ 年比成長 22%，ALDURAZYME 年比成長 40%。我們第二大收入來源 VIMIZIM 與上一季相比表現不均衡，這是我們成熟的全球品牌的典型訂購動態。

Now the strength of PALYNZIQ is based on the opportunity for potent and durable fee reduction to international guideline levels. The unrestricted diet potential that PALYNZIQ offers is an important product characteristic that we think will bring tremendous value to the adolescent PKU population, should we get approval next year. We are pleased with the growth of the enzyme therapies products in the first quarter and expect full year contributions from this important business unit to remain robust.

現在，PALYNZIQ 的優勢在於能夠將費用有效且持久地降低至國際指導水準。PALYNZIQ 提供的不受限制的飲食潛力是一項重要的產品特性，我們認為，如果明年獲得批准，它將為青少年 PKU 人群帶來巨大的價值。我們對第一季酵素療法產品的成長感到滿意，並預計這一重要業務部門的全年貢獻將保持強勁。

In summary, the team executed well in the first quarter, and we look forward to continued strong performance throughout the remainder of 2025. Thank you for your attention, and Greg will now provide an update on R&D. Greg?

總而言之，團隊在第一季表現良好，我們期待在 2025 年剩餘時間內繼續保持強勁表現。感謝您的關注，Greg 現在將提供有關研發的最新進展。格雷格？

Thank you, Cristin. As Alexander mentioned, we recently completed enrollment in our pivotal study for VOXZOGO in hypochondroplasia. We will be sharing the 52-week results next year, and we'll be seeking an approval for 2027, should the data be supportive. Also new today, we are pleased to share that we have reached an agreement with the FDA on an overall clinical development plan for BMN 333. Assuming the Phase I data are supportive, we plan to initiate a registration-enabling study in 2026, supporting our previously stated ambition for 2030 approval date.

謝謝你，克里斯汀。正如亞歷山大所提到的，我們最近完成了針對軟骨發育不全症的 VOXZOGO 關鍵研究的招募。我們將在明年分享 52 週的結果，如果數據支持的話，我們將尋求 2027 年的批准。今天我們也很高興地宣布，我們已與 FDA 就 BMN 333 的整體臨床開發計劃達成協議。假設第一階段的數據支持，我們計劃在 2026 年啟動一項註冊授權研究，以支持我們先前提出的 2030 年批准日期的目標。

We will continue to engage with regulators around the globe to refine our plans in the coming months. In the ongoing Phase I study in healthy volunteers, we've enrolled multiple cohorts and look forward to sharing initial pharmacokinetic data in the second half of the year, with detailed data to be presented at a scientific venue in the first half of 2026.

我們將在未來幾個月繼續與全球監管機構合作，以完善我們的計劃。在正在進行的健康志願者 I 期研究中，我們招募了多個隊列，並期待在今年下半年分享初步藥物動力學數據，並在 2026 年上半年的科學會議上展示詳細數據。

We're also pleased with the numerous data updates across the portfolio so far this year. In March, at the American College of Medical Genetics and Genomics Meeting, we shared data demonstrating favorable safety and strong adherence and real-world clinical practice with VOXZOGO in children under three with achondroplasia. No treatment-related adverse events or dose interruptions were reported among these 63 children followed for up to two years. The study's safety results, including in infants as young as one month old, add to the growing body of evidence supporting early treatment initiation with VOXZOGO, consistent with international treatment guidelines published in the journal Nature Review Endocrinology earlier this year.

我們也對今年迄今投資組合中的大量數據更新感到滿意。今年 3 月，在美國醫學遺傳學和基因組學學會會議上，我們分享了數據，證明 VOXZOGO 對 3 歲以下軟骨發育不全兒童具有良好的安全性和強大的依從性以及真實的臨床實踐。在長達兩年的追蹤中，這 63 名兒童沒有報告與治療相關的不良事件或劑量中斷。這項研究的安全性結果（包括對僅一個月大的嬰兒的研究）進一步證明了使用 VOXZOGO 進行早期治療的必要性，這與今年早些時候在《自然評論內分泌學》雜誌上發表的國際治療指南一致。

Also, at ACMG, PALYNZIQ data demonstrating the importance of sustained fee reduction and the positive impact this can have on health-related quality of life outcomes were presented. Most notably, mood and attention scores for patients achieving sustained Phe levels less than or equal to 120 micromolar per liter were significantly better than those at higher levels, suggesting that sustained Phe in the normal range is it both achievable and may provide additional benefits for adults living with PKU.

此外，ACMG 還展示了 PALYNZIQ 數據，證明了持續降低費用的重要性及其對健康相關生活品質結果的正面影響。最值得注意的是，對於持續 Phe 水平低於或等於每公升 120 微摩爾的病人來說，他們的情緒和注意力得分明顯優於更高水平的病人，這表明持續 Phe 處於正常範圍內是可以實現的，並且可能為患有 PKU 的成年人帶來額外的益處。

These significant and sustained reductions in blood Phe levels, coupled with the opportunity for an unrestricted diet, are unique characteristics of PALYNZIQ, the only enzyme substitute therapy for the treatment of PKU. These benefits demonstrated in adults with PKU give us continued confidence in the treatment profile of PALYNZIQ, including for adolescents, as supported by the positive pivotal data in the 12- to 17-year-old group, as announced in April. We plan to submit for regulatory approvals in both the United States and Europe in the second half of the year.

血液中 Phe 水平的顯著且持續的降低，加上不受限制的飲食的機會，是 PALYNZIQ（唯一用於治療 PKU 的酶替代療法）的獨特特徵。在患有 PKU 的成年人身上所表現出的這些益處使我們對 PALYNZIQ 的治療效果（包括對青少年的治療效果）保持信心，正如 4 月宣布的 12 至 17 歲組積極的關鍵數據所支持的那樣。我們計劃在今年下半年提交美國和歐洲監管部門的批准。

Turning to BMN 351 in Duchenne muscular dystrophy, we plan to publicly present our first clinical update in the second half of this year, including 25-week muscle biopsy data for 4 patients treated at the 6-milligram per kilogram dose cohort. We have done extensive PK/PD modeling based on preclinical data to determine what value at 25 weeks will predict muscle dystrophin levels of 10% or higher at steady state, which we anticipate to occur out at 52 weeks or later.

談到杜氏肌肉營養不良症中的 BMN 351，我們計劃在今年下半年公開發布我們的第一份臨床更新，其中包括以 6 毫克/公斤劑量組治療的 4 名患者的 25 週肌肉活檢數據。我們根據臨床前數據進行了廣泛的 PK/PD 建模，以確定 25 週時的什麼值可以預測穩定狀態下肌肉營養不良蛋白水平達到 10% 或更高，我們預計穩定狀態將在 52 週或更晚時出現。

The model takes into account the tissue half-lives for several chemical species, including for BMN 351, for the skip product production and for generation of dystrophin protein. These values were informed by our experience with BMN 351 in preclinical mouse and nonhuman primate studies, as well as from prior human experience with other phosphorothioate oligonucleotides. The model tells us that levels at 25 weeks can be expected to rise 2x to 3x higher by the time steady state is reached.

該模型考慮了幾種化學物質的組織半衰期，包括 BMN 351、跳躍產品生產和肌肉營養不良蛋白的生成。這些數值是根據我們在臨床前小鼠和非人靈長類動物研究中對 BMN 351 的經驗以及人類先前對其他硫代磷酸酯寡核苷酸的經驗得出的。該模型告訴我們，到達到穩定狀態時，25 週時的水平預計會上升 2 倍到 3 倍。

We also want to measure how these patients feel and function. To do so, we have included several functional measures in this study, though we anticipate such measures will be most informative once steady state is reached. The next update on this program will be shared at a scientific congress in the second half of this year.

我們也想測量這些患者的感覺和功能。為此，我們在本研究中納入了幾項功能性措施，但我們預計，一旦達到穩定狀態，這些措施將最具參考價值。該計劃的下一次更新將在今年下半年的科學大會上分享。

Thank you for your attention today. We look forward to keeping you apprised of our progress as we continue to advance our high-impact candidates through the pipeline. We will now open the call to your questions. Operator?

感謝您今天的關注。我們期待隨時向您通報我們的進展情況，我們將繼續透過人才管道培養具有高影響力的候選人。我們現在開始回答你們的問題。操作員？

(Operator Instructions) Phil Nadeau, TD Cowen.

（操作員指示）Phil Nadeau，TD Cowen。

Two financial ones. First on VOXZOGO, you've mentioned a couple of times about H2 being larger than H1 and also the revenue in the course through Q2 being relatively similar. I'm just curious whether -- does that mean a decline in Q2 revenue? It does look like revenue grew a bit from Q4 to Q1. So if revenue is approximately intermediate between those two, maybe there'll be a down quarter, Q2?

兩個財務問題。首先關於 VOXZOGO，您曾多次提到下半年的業績大於上半年，整個第二季的營收也相對相似。我只是好奇——這是否意味著第二季收入會下降？看起來第四季的營收確實比第一季有所成長。因此，如果收入大約介於這兩者之間，那麼第二季度的收入可能會下降嗎？

And then second financial question on exposure to tariffs. I think your guidance as to the current tariff situation is very clear. Could you give us some sense of how your financials could be impacted should the US impose a 25% tariff on EU pharmaceuticals? And then -- maybe should that situation be retaliated against with a 25% tariff from the EU on the US?

然後是有關關稅影響的第二個財務問題。我認為您對當前關稅情況的指導非常明確。您能否告訴我們，如果美國對歐盟藥品徵收 25% 的關稅，您的財務狀況將受到怎樣的影響？那麼——歐盟是否應該對美國徵收 25% 的關稅以進行報復？

Thanks, Phil. This is Brian. I'll take both of those. Appreciate the questions. First on VOXZOGO. I think you heard accurately in terms of the trends you're observing coming out of Q4 last year here in Q1 and then into the first half of this year. We had previously commented that we expected most of the VOXZOGO revenue growth to come in the second half of the year.

謝謝，菲爾。這是布萊恩。我會接受這兩個。感謝您的提問。首先在 VOXZOGO 上。我認為您準確地聽到了您觀察到的趨勢，即去年第四季度、今年第一季以及今年上半年的趨勢。我們之前曾評論說，我們預計 VOXZOGO 的大部分收入成長將在今年下半年實現。

And the first thing I'd point to is what we're observing are global order dynamics, which are different from what shows up in the enzyme therapy business from time to time that the quarters would be a handful of those large bolus orders from select international customers that can either accumulate to an anomalous quarter or be missing from a quarter. It's less that and more just the dynamics of VOXZOGO being available in now, 49 markets. And it doesn't take much for some of the purchasing patterns between, again, the end of '24, Q3-Q4 into Q1-Q2 for those to look flattish. But importantly, at the same time, we are steadily increasing patients from quarter-to-quarter. So it's just an accumulation of dynamics across all of those markets.

我首先要指出的是，我們觀察到的是全球訂單動態，這與酶療法業務中不時出現的情況不同，酶療法業務中每個季度都會出現來自特定國際客戶的少量大宗訂單，這些訂單可能會累積到一個異常季度，也可能會在某個季度缺失。這還不算什麼，VOXZOGO 目前已在 49 個市場推出。而且，在 24 年底、第三季至第四季和第一季至第二季之間，有些購買模式並不需要花費太多時間就能顯得平淡。但重要的是，與此同時，我們的患者數量正在逐季度穩定增加。所以這只是所有這些市場動態的累積。

And then we see it slipped in the second half of the year when we expect revenue to increase more substantially. So that's the key VOXZOGO matter. And on tariffs, you heard accurately because we have immaterial exposure in our business to China, Mexico and Canada, we do not have a material impact, and our reaffirmed guidance today includes any modest or immaterial impacts from tariffs in those regions.

然後，我們看到下半年收入下滑，而我們預計下半年收入將大幅成長。這就是 VOXZOGO 的關鍵問題。關於關稅，您聽到的很準確，因為我們的業務與中國、墨西哥和加拿大的接觸並不重大，所以我們沒有受到重大影響，我們今天重申的指導方針包括這些地區關稅帶來的任何適度或非實質性的影響。

In terms of potential future pharmaceutical tariffs, we are modeling all scenarios and evaluating all of the potential mitigating tactics. We're going to hold off on speaking to specifics, including quantifying any of those scenarios until we have more clarity and announcements and certainty in terms of what pharmaceutical tariffs could look like, but I can assure you that we're not just looking at all scenarios, but all potential levers.

就未來潛在的藥品關稅而言，我們正在模擬所有情境並評估所有潛在的緩解策略。我們將暫時不談論具體細節，包括量化任何這些情景，直到我們對藥品關稅有更清晰的認識和公告以及確定性，但我可以向你們保證，我們不僅會考慮所有情景，還會考慮所有潛在的槓桿。

Many of those are in the same categories that you're hearing some of the larger biopharmas discuss on their Q1 calls. That includes global supply chain strategies, which also for us includes our global manufacturing network, managing inventory levels, our global intellectual property rights. And then lastly, monitoring potential global tax reform in connection with or in response to the overall tariff.

其中許多都屬於您聽到的一些大型生物製藥公司在第一季電話會議上討論的同一類別。這包括全球供應鏈策略，對我們來說還包括我們的全球製造網絡、管理庫存水準、我們的全球智慧財產權。最後，監測與整體關稅相關或響應整體關稅的潛在全球稅收改革。

So we've got a dynamic global business. Our products are sourced from both the US and outside of the US. I'll share that we are a net exporter of products in the US due to our significant California-based manufacturing site.

因此，我們擁有一個充滿活力的全球業務。我們的產品來自美國國內和美國境外。我想說的是，由於我們在加州擁有重要的製造基地，我們是美國產品的淨出口國。

And then just a reminder as well that from an overall exposure to US sales imports, most of our sales are outside of the US. Roughly 1/3 of our total sales are US sales, and 2/3 outside of the US. So those are potentially insulating factors should we see pharmaceutical tariffs.

也要提醒的是，從美國銷售進口的整體情況來看，我們的大部分銷售都在美國以外。我們總銷售額的約 1/3 來自美國，2/3 來自美國以外。因此，如果我們看到藥品關稅，這些都是潛在的隔離因素。

But we're going to hold off on speculating on any details at this time. Appreciate the interest, though.

但我們暫時不會對任何細節進行猜測。不過，我很感激你的關注。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Congrats on all the progress. This is Tommie on for Salveen. Just wondering if we can get an update on your interest and maybe timing for BD after all of the meetings that you had in January? And when we think about the data that you'll give us for BMN 333 this year, can you maybe characterize the level of detail we'll get before you kind of present the full data at the Congress next year?

祝賀你取得的所有進展。這是 Tommie 為 Salveen 上場。我只是想知道，在您一月份參加所有會議之後，我們是否可以了解您對 BD 的興趣和時間安排的最新消息？當我們考慮您今年將為我們提供 BMN 333 的數據時，您能否描述一下在明年的大會上展示完整數據之前我們將獲得的詳細程度？

Thanks very much, Tommie. I'll handle the question on BD and then hand over to Greg. So we continue to be very excited about the potential for BD for BioMarin based on our strong capabilities. And also, obviously, the state of the capital markets. We've been approaching it very methodically.

非常感謝，湯米。我會處理有關 BD 的問題，然後交給 Greg。因此，基於我們強大的能力，我們繼續對 BD 為 BioMarin 帶來的潛力感到非常興奮。顯然，還有資本市場的狀況。我們一直在非常有條不紊地處理此事。

We've got a great team and capabilities in place. We've got a very clear strategy, which we outlined that communicated to the outside world last year. And we've been looking systematically at opportunities.

我們擁有一支優秀的團隊和能力。我們有一個非常明確的策略，我們去年就已向外界進行了概述。我們一直在有系統地尋找機會。

And just to reiterate what we're looking at is things which lined up with what BioMarin is really good. So genetically defined conditions. We're looking at clinical stage assets in particular, as well as, obviously, earlier assets, always done that. And particularly highlighting ones that are aligned with our business unit structure where we really think we have a strength and a right to win.

再次重申一下，我們正在關注的是與 BioMarin 真正優點相符的東西。所以是基因定義的條件。我們正在特別關注臨床階段資產，當然還有早期資產，我們一直都是這樣做的。特別要強調的是那些與我們的業務部門結構一致的，我們確實認為我們有實力和權利贏得勝利。

So yes, everything is very much on track. We continue to focus on doing at least one business development deal this year. We're looking forward to providing updates as when that makes sense. And obviously, as the market continues to develop, it only creates more value from our perspective and makes those deals even more attractive from an investor standpoint. And with that, I'll hand over to Greg.

是的，一切都在按計劃進行。我們今年將繼續致力於完成至少一項業務發展交易。我們期待在適當的時候提供更新。顯然，隨著市場不斷發展，從我們的角度來看，它只會創造更多的價值，並從投資者的角度來看，使這些交易更具吸引力。說完這些，我就把麥克風交給格雷格。

Thanks, Alexander. With regard to BMN 333, just as a quick reminder, we have an ongoing Phase I study. It is in healthy volunteers, not in patients. So the primary purpose of this study, of course, will be to look at single dose safety, but also the PK profile. That is the data.

謝謝，亞歷山大。關於 BMN 333，簡單提醒一下，我們正在進行第一階段的研究。它存在於健康志願者身上，而不是病人身上。因此，本研究的主要目的當然是檢視單劑量安全性以及 PK 概況。這就是數據。

Again, we're actually marching right through the study very efficiently. We're several cohorts in at this point. And we anticipate before the end of the year that we'll be able to provide a top line update with regard to whether or not that data is supportive of us moving forward. The more detailed PK data and totality of the Phase I, we anticipate in the first half of next year, we'll be releasing that publicly.

再次，我們實際上正在非常有效率地完成這項研究。我們現在有幾個隊伍。我們預計在今年年底之前，我們將能夠提供最新的數據更新，說明這些數據是否支持我們繼續前進。我們預計在明年上半年公開發布更詳細的 PK 數據和第一階段的整體情況。

Joseph Schwartz, Leerink Partners.

Leerink Partners 的 Joseph Schwartz。

This is [Jenny] on for Joe. I think for previously, you guys have mentioned that VOXZOGO has penetrated just under 20% of the market in achondroplasia as of the second quarter last year. Can you talk a little bit more about what strategies you're implementing to drive further adoption among patients? And is this something that you're going to have to reach out to physicians? And what are the main areas of possible improvement here and how you see this trending over time?

我是[珍妮]，為喬介紹情況。我記得之前你們提到過，截至去年第二季度，VOXZOGO 在軟骨發育不全症領域的市佔率已接近 20%。您能否進一步談談您正在實施哪些策略來推動患者進一步採用？您是否需要聯絡醫生來解決此問題？這裡可能改進的主要領域是什麼？您如何看待這種趨勢？

Yes. Thank you so much for the question, Jenny. This is Cristin Hubbard. So a great question about the penetration of VOXZOGO. We have several strategies that we are in the process of implementing that I think will certainly help us to further drive growth. And in particular, when I think about the US market, which is our largest single market opportunity, where we're really focused on is driving adoption across all age groups.

是的。非常感謝你的提問，珍妮。這是克里斯汀·哈伯德。因此，關於 VOXZOGO 的滲透率存在一個很好的問題。我們正在實施幾項策略，我認為這些策略肯定有助於我們進一步推動成長。特別是當我想到美國市場時，它是我們最大的單一市場機遇，我們真正關注的是推動所有年齡層的人採用它。

Now as we previously reported, we've had quite an uptick in numbers in the 0 to 4 population. And just to remind you that we just got that label expansion at the end of 2023. So our new patient starts have been very strong in the 0 to 4 age group, in which case, this is very well aligned with the consensus guidelines that we saw come out earlier this year, which recommends early diagnosis and early treatment with VOXZOGO. So we have strategies and tactics in place targeting that age group, starting at infancy.

正如我們之前報導的那樣，0 至 4 歲人口的數量已經有了相當大的增長。需要提醒您的是，我們剛剛在 2023 年底獲得了該標籤擴展。因此，我們的 0 至 4 歲年齡組的新患者數量非常強勁，在這種情況下，這與我們今年早些時候發布的共識指南非常一致，該指南建議使用 VOXZOGO 進行早期診斷和早期治療。因此，我們從嬰兒期開始就制定了針對該年齡層的策略和策略。

And then, of course, we don't want to forget about the importance of slightly older patients, so in the 5 plus age group. And that's where we're definitely still targeting. There's still opportunity there in the US to continue to target those patients. I will say that our strategies, in particular, are really in and around driving awareness of the medicine than the fact that there is a treatment option available, and so we're looking at investing in initiatives that will help us there.

當然，我們也不會忘記年齡稍大的患者的重要性，也就是 5 歲以上的年齡層。這絕對是我們的目標。美國仍然有機會繼續瞄準這些患者。我想說的是，我們的策略實際上是圍繞著提高人們對藥物的認識，而不是關注是否存在治療選擇這一事實，因此，我們正在考慮投資能夠幫助我們實現這一目標的舉措。

This will, in large part, help us to expand the prescriber base. And so what we're looking at is really making sure that we're expanding the prescriber base. And this is true across various specialties.

這在很大程度上有助於我們擴大處方者基礎。因此，我們真正要考慮的是確保擴大處方者基礎。各個專業領域都是如此。

But where we see the most growth in terms of prescribers is in the pediatric endocrinologists, which is very in line with our strategies to expand there. We're also investing in increased field personnel, again, to target prescribers to ensure that we're driving awareness and adoption therein. And then when we think outside of the US, where we're looking at is continuing to look for those kind of access pathways, awareness pathways, but also importantly, we'll continue to open new markets, which will expand further penetration.

但我們看到處方數量增長最快的是兒科內分泌科醫生，這非常符合我們在那裡擴張的策略。我們也投資增加現場人員，再次以處方人員為目標，以確保我們能夠提高他們的認識和採用率。當我們考慮美國以外的時候，我們關注的是繼續尋找那種進入途徑、認知途徑，但同樣重要的是，我們將繼續開拓新市場，從而進一步擴大滲透率。

Then I can say -- I was going to say lastly, I think that all of this has really been enhanced in our ability to do this to execute in a focused manner because of the business unit structure that we put in place. This has been a really exceptional way for us to really drive into the market insights, leading to strategy and execution in a really focused and agile way.

然後我可以說——我最後要說的是，我認為由於我們建立的業務部門結構，所有這些都確實增強了我們以專注的方式執行的能力。對我們來說，這是一種真正深入了解市場、以真正專注和敏捷的方式製定和執行策略的特殊方式。

Akash Tewari, Jefferies.

Akash Tewari，傑富瑞。

This is [Aki] on for Akash. Just on the DMD corrector, 351. When we looked at the recently published mouse data, it looks like there's some mild liver signals in those mouse models at the higher exposure and some inflammation in the liver and muscle in those mice. So given those safety signals, how are you thinking about your ability to dose chronically? And is there any data that you're collecting that we can see in the upcoming readout that could potentially make us more comfortable on safety?

這是 [Aki] 為 Akash 主持的。就在DMD校正器上，351。當我們查看最近發布的小鼠數據時，似乎在較高暴露水平下，這些小鼠模型中出現了一些輕微的肝臟訊號，並且這些小鼠的肝臟和肌肉出現了一些發炎。那麼，考慮到這些安全訊號，您如何看待自己長期服藥的能力？並且，我們能否在即將發布的讀數中看到您收集的任何數據，從而有可能讓我們對安全更加放心？

Yes. Thanks for the question. This is Greg Friberg. These observations or class effects for the ASO categories. And so from that standpoint, we're not surprised to see at high dose levels in some of our toxicologic studies that we're seeing some of these end organ toxicities.

是的。謝謝你的提問。我是格雷格·弗里伯格。這些觀察值或類別效應針對的是 ASO 類別。因此，從這個角度來看，我們並不驚訝地發現，在一些毒理學研究中，高劑量水平會導致一些終末器官毒性。

We're watching them very closely. And in fact, we selected a chemistry type, this phosphorothioate instead of other available chemistry classes because we do believe that this is a case where it's all about opening that therapeutic window. Again, there's two ways to address the therapeutic window. One is to limit toxicity. The other way is to drive the potency of the molecule.

我們正在密切關注他們。事實上，我們選擇了一種化學類型，這種硫代磷酸酯，而不是其他可用的化學類別，因為我們確實相信這是一個關於打開治療窗口的案例。再次，有兩種方法可以解決治療窗口問題。一是限制毒性。另一種方法是提高分子的效力。

And we've engineered this molecule to try to really take advantage of, like we talked about previously, this novel skip site and some other chemical factors, again, that get the drug where we want it to be. Those are the open questions, I think, for almost any molecule in the space, and we're watching patients very closely for a variety of toxicities.

我們設計了這種分子，試圖真正利用這種新的跳躍位點和一些其他化學因素，就像我們之前談到的，讓藥物到達我們想要的位置。我認為，對於該領域中的幾乎所有分子來說，這些都是懸而未決的問題，我們正在密切關注患者的各種毒性。

We will be presenting our data from our 6-milligram per kilogram cohort in the second half of this year. And you can expect in addition to dystrophin assays on muscle biopsies that we would present the totality of our safety data that's available at that time.

我們將在今年下半年公佈每公斤 6 毫克隊列的數據。而且您可以期待，除了肌肉活檢中的肌肉營養不良蛋白檢測之外，我們還將提供當時可用的全部安全數據。

Jessica Fye, JPMorgan.

潔西卡費伊（Jessica Fye），摩根大通。

So BioMarin continues to execute across the business. However, the market seems worried about long-term competition for VOXZOGO. Can you talk about how you think you can best address the market's perception of VOXZOGO's long-term value, particularly beyond 2030?

因此，BioMarin 將繼續執行整個業務。然而，市場似乎擔心 VOXZOGO 的長期競爭。您能否談談您認為如何才能最好地解決市場對 VOXZOGO 的長期價值的看法，特別是 2030 年以後的價值？

I'll start on the commercial execution here in the near term. And if you want to talk about some of the life cycle management, I think that would be probably nice. But thanks for the question, Jess. So I certainly recognize where you're coming from in terms of the market perception. And what I can really say is that with VOXZOGO, where we're really focused in terms of our strategies and where I think that this is going to be something that will be quite powerful for us is really focused in and around this notion of a start-and-stay treatment paradigm.

我將在近期開始這裡的商業執行。如果您想談論一些生命週期管理，我認為那可能會很好。但謝謝你的提問，傑西。因此，我當然知道您從市場角度來看待這個問題。我可以真正說的是，透過 VOXZOGO，我們真正關注的是我們的策略，我認為這對我們來說將是一個非常強大的東西，它真正關注的是開始和停留治療模式的概念。

And really getting patients to start. And again, reminding everybody that our label starts at infancy, which I think is a unique differentiator here in the near term, it's really based on our ability to helps families and prescribers feel comfortable with the growing body of evidence, which includes 6,000 plus patient years of efficacy and safety data. We've got a tremendous -- and I know, Greg, you can speak to some of this -- growing body of evidence on the overall health benefits that go far beyond height, which I think is really important to treaters and families alike.

並真正讓患者開始行動。再次提醒大家，我們的標籤從嬰兒期開始，我認為這是短期內的一個獨特差異化因素，它實際上基於我們幫助家庭和處方者對越來越多的證據感到滿意的能力，其中包括 6,000 多名患者多年的療效和安全性數據。我們有大量的證據——我知道，格雷格，你可以談談其中的一些——表明它對整體健康的益處遠遠超出了身高，我認為這對治療師和家庭都非常重要。

We've got this broad label in terms of starting in infancy, which I think aligns nicely with the consensus guidelines. And importantly, we have a growing footprint in countries outside the world. Reminding everybody that only 10% of the total addressable patient population is in the United States. And we have an incredible commercial footprint that goes into many, many countries. As you guys know, we're now 49 countries we have VOXZOGO access in, and we're looking to build that into greater than 60 countries by 2027.

就從嬰兒期開始而言，我們有這個廣泛的標籤，我認為這與共識指南非常吻合。重要的是，我們在世界其他國家的影響力正在不斷擴大。提醒大家，可尋址患者總數中只有 10% 在美國。我們的商業足跡遍佈許多國家，令人驚嘆。如你們所知，現在我們在 49 個國家/地區擁有 VOXZOGO 存取權限，我們希望在 2027 年將這一範圍擴大到 60 多個國家。

So we see the growth trajectory as something that we can maintain. And as you know, we've given full year guidance to a little over 25% at the midpoint for the year, and we'll continue with a 25% CAGR out into the future. But Greg, I don't know if you maybe should speak to some of the life cycle options we have as well?

因此，我們認為成長軌跡是可以維持的。如您所知，我們已將全年預測定為略高於 25% 的年增長率，並且未來我們將繼續保持 25% 的複合年增長率。但是格雷格，我不知道你是否也應該談談我們的一些生命週期選項？

Yes. Thanks, Cristin. And from an R&D perspective, we are going to continue to try to leverage, again, that 6,000-patient year, it's about 4,000 individual patients and growing experience to actually put the data out there with regard to how we're improving the health and wellness of these patients with achondroplasia. We get caught up in, I think, AGV numbers sometimes, but we have to remember that the burden of disease that we really want to address are things that go well beyond that.

是的。謝謝，克里斯汀。從研發角度來看，我們將繼續嘗試利用每年 6,000 名患者（約 4,000 名個別患者）的經驗，實際提供有關如何改善這些軟骨發育不全患者的健康和保健的數據。我認為，我們有時會陷入 AGV 數字的泥潭，但我們必須記住，我們真正想要解決的疾病負擔遠不止於此。

And so data with regard to craniofacial volume, foramen magnum size, body proportionality, quality of life data and of course, bone strength and bone integrity, these are the kind of data that we will -- we have already put out, but we're also going to continue to grow and put out. What patients and their families want is they want a safe and dependable drug. And we think that that's exactly what VOXZOGO is. It's a targeted therapy for -- that's tailored for these patients with achondroplasia. And again, that long-term experience, we're going to continue to publish that.

因此，關於顱面體積、枕骨大孔大小、身體比例、生活品質數據，當然還有骨骼強度和骨骼完整性的數據，這些都是我們已經發布的數據，但我們也將繼續成長和發布。病人和家屬想要的是一種安全可靠的藥物。我們認為這正是 VOXZOGO 的特色。這是一種針對軟骨發育不全患者的標靶療法。再次強調，我們將繼續發布這項長期經驗。

We're also developing the molecule and other stature related disorders. And I think we've spoken about that previously, but we think that there's an opportunity here to continue to develop the agent. We also, of course, are invested in our next-generation agent, which is BMN 333. Our goal with BMN 333 isn't just a more convenient version of CNP. It's to actually increase the free CNP exposure that we can reach in the patients.

我們也正在開發分子和其他與身材相關的疾病。我認為我們之前已經討論過這個問題，但我們認為這裡有機會繼續開發代理。當然，我們也投資了我們的下一代藥劑，即 BMN 333。我們對 BMN 333 的目標不僅僅是打造更便利的 CNP 版本。這其實是為了增加患者體內可接觸到的免費 CNP 劑量。

And so that recent agreement with the FDA moving forward into what a pivotal plan might look like, we see that as an incremental positive. And we're very much looking forward to the PK data that we'll see later this year. So again, a lot of confidence that VOXZOGO is a safe and effective therapy.

因此，我們最近與 FDA 達成的協議正在推進一項關鍵計劃，我們認為這是一個積極的進步。我們非常期待今年稍後看到的 PK 數據。因此，我們再次確信 VOXZOGO 是一種安全有效的治療方法。

Should we expect the same endpoint for 333 in a pivotal trial as for VOXZOGO?

我們是否應該預期 333 在關鍵試驗中的終點與 VOXZOGO 相同？

So we're envisioning that we will do a comparative effectiveness study versus VOXZOGO, and we'll be looking at similar endpoints to what has been studied in previous examples.

因此，我們設想對 VOXZOGO 進行一項比較有效性研究，並且我們將研究與前面範例中研究過的類似的終點。

Paul Matteis.

保羅·馬泰斯。

I had one for Brian and one clinical question. Brian, I wanted to just clarify as it relates to VOXZOGO over the past couple of quarters and what you're seeing going into 2Q, has the net price on a global basis of the drug changed? Just curious if their price has gone down a bit as either diversified into other markets and your expectation there?

我有一個問題想問布萊恩，還有一個臨床問題。布萊恩，我想澄清一下，就過去幾季的 VOXZOGO 而言，以及您看到的第二季度的情況，該藥品的全球淨價是否發生了變化？只是好奇，由於它們向其他市場多元化發展，其價格是否有所下降，您對此有何預期？

And then as it relates to the 333 pivotal, that was super interesting to kind of get the color on a comparative design. Are you looking to actually show superiority? Is it going to be powerful noninferiority? I mean maybe it's too early to say, but given your conviction that higher exposure may drive greater efficacy, what do you see the opportunity to show there?

然後，當它與 333 個關鍵點相關時，在比較設計上獲得顏色是非常有趣的。您是否真的想展現自己的優越感？這是否會具有強大的非劣效性？我的意思是，也許現在說還為時過早，但鑑於您確信更高的曝光率可能會帶來更大的功效，您認為這其中有什麼機會可以展示？

This is Greg. Maybe I'll take the 333 question because it's a quick answer. Yes, we are looking for superiority and growth dynamics from a higher exposure of CNP.

這是格雷格。也許我會回答第 333 個問題，因為它是一個快速答案。是的，我們正在尋找更高的 CNP 曝光度帶來的優勢和成長動力。

Thanks, Paul, for the question. Mine is likewise a quick answer because -- and it's a great question when you talk about demand increasing and not seeing the same correlation in revenue for these couple of quarters. We are not observing -- not seeing any pricing dynamics. It's truly just the lack of correlation market by market. That just happens to show up here in Q1 and possibly in Q2, no price factored in.

謝謝保羅提出這個問題。我的回答同樣很快，因為——當你談到需求增加，但這兩個季度的收入卻沒有出現相同的相關性時，這是一個很好的問題。我們沒有觀察——沒有看到任何定價動態。這確實只是市場之間缺乏關聯性。這恰好出現在第一季度，也可能出現在第二季度，沒有考慮價格因素。

Ellie Merle, UBS.

瑞銀的艾莉·梅爾（Ellie Merle）。

This is [Jasmine] on for Ellie. So what's the latest on timing for VOXZOGO and other growth disorders like [ISS and shocks]? And then how quickly do you think that you could move 333 here? So would you want to wait for VOXZOGO clinical success here before studying 333 in these indications? Or is that something you'd want to do sooner?

這是 [Jasmine] 為 Ellie 演唱的。那麼，VOXZOGO 和其他生長障礙的最新治療時機是什麼？[國際太空站與衝擊]？那麼，您認為您能多快將 333 移到這裡？那麼，您是否願意等待 VOXZOGO 取得臨床成功後再研究 333 在這些適應症中的作用？還是這是您想早點做的事情？

Thank you for the question. This is Greg Friberg, again. With regard to the Noonan's, Turner and shocks basket that we have as well as idiopathic short stature, both of those protocols are open for enrollment and are continuing to progress. We anticipate that we will have data from those programs that would enable to begin pivotal studies in 2027. So we remain on track for those goals.

謝謝你的提問。我是 Greg Friberg。關於我們的努南氏症候群、特納氏症和衝擊症候群以及特發性矮小症，這兩項方案都已開放註冊並正在繼續推進。我們預計，我們將從這些項目中獲得數據，以便在 2027 年開始關鍵研究。因此，我們仍在朝著這些目標前進。

With regard to the role that 333 would play in additional indications, just as a reminder, we still are working through with 333. Once we've moved beyond healthy volunteers, there will be both dose ranging as well as the effectiveness studies to come thereafter. And that's the agreement, again, that we referred to with the FDA. A long way of saying that these reveals of information are actually going to line up quite nicely so that we can make decisions when we have the complete profile for 333 to determine what the future plans would be. Right now, the discussions with 333 that we've been talking about have been achondroplasia related.

關於 333 在附加適應症中將發揮的作用，提醒一下，我們仍在努力完成 333。一旦我們不再局限於健康志願者，接下來就會進行劑量範圍和有效性研究。這是我們與 FDA 再次提到的協議。長話短說，這些資訊的披露實際上會排列得相當整齊，以便我們在掌握 333 的完整資料後能夠做出決定，確定未來的計劃。目前，我們與 333 的討論與軟骨發育不全有關。

Cory Kasimov, Evercore ISI.

Cory Kasimov，Evercore ISI。

This is [Adi] on for Cory. Wanted to ask you if you can share how the US versus ex-US sales have evolved in the first quarter for VOXZOGO? And what trends do you expect to see going forward into the rest of the year?

這是 [Adi] 為 Cory 上場。想問您是否可以分享 VOXZOGO 第一季美國和美國以外地區的銷售情況如何？您預計今年剩餘時間會出現哪些趨勢？

Yes. Thank you so much for the question. This is Cristin. And as you know, last quarter, we gave specifics on precisely that, which is the US versus outside US revenues for VOXZOGO. And we did that strictly so we could clarify the significant contributions that come from outside the US. And given that the ex-US weight of the revenues is approximately 75% total of vox revenues, we do expect this split to fluctuate just a little bit quarter-over-quarter. And that goes back to what Brian had mentioned about ordering patterns becoming a little bit more bumpy as we turn into a more mature brand, which is very commensurate with other products in our portfolio.

是的。非常感謝您的提問。這是克里斯汀。如您所知，上個季度我們給出了具體細節，即 VOXZOGO 在美國和美國以外地區的收入。我們嚴格這樣做是為了明確來自美國以外的重大貢獻。鑑於美國以外的收入佔 vox 總收入的約 75%，我們預計這一比例將逐季略有波動。這又回到了 Brian 提到的，隨著我們成為一個更加成熟的品牌，訂購圖案的過程會變得更加坎坷，這與我們產品組合中的其他產品非常相稱。

But overall, we expect the split today to be roughly around 75%. And in the long term, what we expect is that it will mirror that of our other products in our portfolio, which is where you have about 1/3 of the revenues coming from the US and 2/3 coming from outside the US.

但總體而言，我們預計今天的分割率大約在 75% 左右。從長遠來看，我們預計它將與我們產品組合中的其他產品的情況相似，其中約 1/3 的收入來自美國，2/3 來自美國以外。

Great. I'll jump back in the queue for the rest of the question.

偉大的。我將回到隊列中回答剩餘的問題。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

I have two sets of questions. First one is regarding also the VOXZOGO franchise. So maybe the 333, can you help us understand because you have a healthy volunteer data and mainly is the PK data, how do you define that will be the top line data you shared with us, that will be good enough that defined as a supportive to start your registration trial? And will you only identify one dose for your registration trial?

我有兩組問題。第一個也與 VOXZOGO 特許經營有關。所以也許是 333，您能幫助我們理解嗎？因為您有健康志願者的數據，主要是 PK 數據，您如何定義這將是您與我們分享的最重要的數據，這些數據是否足夠好，可以定義為支持開始您的註冊試驗？您的註冊試驗是否只確定一種劑量？

And then a related question, I know there is a competitor running [CNP] plus growth hormone studies. Any thoughts there? We know historically, growth hormone didn't work. So maybe any thoughts there regarding CNP plus growth human study? And the third part, very quickly on the manufacturing side for VOXZOGO, do you have a manufacturing sites both in the US and the ex-US?

然後是一個相關的問題，我知道有一個競爭對手正在進行 [CNP] 加生長激素研究。有什麼想法嗎？我們知道，從歷史上看，生長激素是不起作用的。那麼，關於 CNP 加生長人類研究，您有什麼想法嗎？第三部分，關於 VOXZOGO 的製造方面，您在美國和美國以外都有製造基地嗎？

So thank you, Gena. First question, with regard to 333, you're correct. We will have PK data of all the species. So we'll have not only BMN 333, but also free CNP levels. Our goal for that study is to see multifold increases in sustained exposure levels for free CNP.

所以謝謝你，吉娜。第一個問題，關於 333，您說得對。我們將擁有所有物種的 PK 數據。因此，我們不僅有 BMN 333，還有免費的 CNP 等級。我們進行此項研究的目標是使遊離 CNP 的持續暴露水準倍增。

And that data will then unlock what comes next. That next study, while we call it one protocol, which it is, it is a multipart protocol that involves both a dose-ranging portion as well as a comparative effectiveness portion. And so in that regard, the data that we'll be revealing later this year will be the ungating to move into those patients with achondroplasia to do that dose-ranging study. To pick that final dose, again, that will be in the comparative effectiveness side. On the growth hormone side, I think you've actually framed it quite nicely.

這些數據將揭開接下來發生的事情的謎團。下一項研究，雖然我們稱之為一個方案，但它是一個多部分方案，涉及劑量範圍部分以及比較有效性部分。因此，在這方面，我們將在今年稍後公佈的數據將成為對軟骨發育不全患者進行劑量範圍研究的開端。再次強調，選擇最終劑量將取決於比較有效性。在生長激素方面，我認為您實際上已經很好地闡述了這一點。

We would not be surprised at all to see that if you combine growth hormone with CNP and achondroplasia patients, that you would see an increase in AGV at 6 or 12 months, maybe even out at 2 years. But historically, the challenge for growth hormone hasn't been about those short-term benefits. It's been about whether they translate into meaningful increases in final adult height.

如果將生長激素與 CNP 和軟骨發育不全患者結合起來，我們一點也不會感到驚訝，您會在 6 個月或 12 個月時看到 AGV 增加，甚至可能在 2 年後增加。但從歷史上看，生長激素面臨的挑戰並不在於這些短期利益。關鍵在於它們是否能夠轉化為最終成年身高的顯著增加。

And as you mentioned, they've been transient. That's been the challenge. This is, of course, why growth hormone isn't actually routinely recommended by expert guidelines or regulators around the globe except for some unique regions.

正如您所說，它們是短暫的。這就是挑戰。當然，這就是為什麼除了一些特殊地區外，全球各地的專家指南或監管機構實際上並不常規推薦使用生長激素的原因。

We also should remember that growth hormone really in this discussion of height is really not the most important measure that we should be talking about. This health and wellness of the patients is, of course, the most important factor. And we haven't seen that with growth hormone, at least to the date that the kind of evidence beyond height could be achieved in patients with achondroplasia.

我們也應該記住，在身高討論中，生長激素實際上並不是我們應該談論的最重要的指標。當然，病人的健康和安康是最重要的因素。而我們還沒有在生長激素方面看到這一點，至少到目前為止，在軟骨發育不全患者身上還沒有發現超越身高的證據。

On the contrary, growth hormone really has added problems for patients. There's been acceleration of bone age. We've seen worsening proportionality at different times, of course. And when you just look at the label, there's cardiovascular and metabolic disturbances.

相反，生長激素確實給患者增加了麻煩。骨齡正在加速成長。當然，我們在不同時期都看到比例惡化的情況。當你看標籤時，你會發現有心血管和代謝紊亂。

And then one unique factor that's been brought up by some of the treating physicians, things like [tonsilar] hypertrophy that don't seem like they'd be a big deal in most children actually in children with airway obstruction can be a very challenging problem. So clearly, these need to be watched very closely with regard to growth hormone. What we're very pleased about with VOXZOGO is, remember, these kids aren't even growth hormone deficient. But what VOXZOGO brings is a targeted therapy. We think, again, we've demonstrated the effects on all those areas beyond height.

一些治療醫生也提出了一個獨特的因素，像扁桃體肥大這樣的問題對於大多數兒童來說似乎不是什麼大問題，但對於患有氣道阻塞的兒童來說，這可能是一個非常棘手的問題。因此顯然，需要密切注意生長激素。我們對 VOXZOGO 感到非常高興，請記住，這些孩子甚至沒有生長激素缺乏。但VOXZOGO帶來的是針對性治療。我們認為，我們再次證明了其對高度以外所有領域的影響。

We talked about craniofacial volume and others in a previous answer and all while maintaining bone health. That's what we think these patients need. That's what they want a safe and dependable targeted therapy for their disease.

我們在先前的回答中討論了顱面體積和其他問題，同時保持骨骼健康。我們認為這就是這些病人所需要的。他們想要的是一種安全可靠的針對性治療手段來治療他們的疾病。

Thanks, Greg. Hi Gena, this is Brian. I'll take your question on VOXZOGO manufacturing. VOXZOGO drug substance is sourced from the United States.

謝謝，格雷格。你好，吉娜，我是布萊恩。我將回答您關於 VOXZOGO 製造的問題。VOXZOGO藥物成分來自美國。

Kostas Biliouris, BMO Capital Markets.

Kostas Biliouris，BMO 資本市場。

Congrats on the progress. Maybe one question for Greg on BMN 333. There is a recent presentation by Children's National Hospital at ESPE that shows that there is no really meaningful correlation between VOXZOGO PK and growth outcomes in hypochondroplasia. So given this data, I wonder to what extent will we be able to draw conclusions about BMN 333 outcomes based on the PK data that we will see in 2025?

恭喜你取得進展。也許我想問 Greg 關於 BMN 333 的一個問題。ESPE 兒童國家醫院最近發表的一份報告顯示，VOXZOGO PK 與軟骨發育不全的生長結果之間並沒有真正有意義的相關性。因此，根據這些數據，我想知道我們在多大程度上能夠根據 2025 年看到的 PK 數據得出有關 BMN 333 結果的結論？

Thanks for your question. I think when we talk about VOXZOGO PK, we also have to recognize the challenges when a drug has about a 30 to 60 minute half life of actually getting the complete profile. Trough PK becomes very -- well, trough PK, if you're going to measure, a very low point is easy. But measuring that full profile can be a challenge. There is a fundamental difference between the PK profile of VOXZOGO and what we expect to see in BMN 333. Of course, rather than a sawtooth pattern, we expect to see much more of a continuous relief.

謝謝你的提問。我認為，當我們談論 VOXZOGO PK 時，我們也必須認識到，當一種藥物的半衰期約為 30 到 60 分鐘時，獲得完整的特性曲線所面臨的挑戰。通過 PK 變得非常 - 好吧，通過 PK，如果你要測量，那麼非常低的點很容易。但衡量完整的概況可能是一個挑戰。VOXZOGO 的 PK 概況與我們期望在 BMN 333 中看到的概況存在根本區別。當然，我們期望看到的不是鋸齒狀的形態，而是連續的浮雕。

And fundamentally different approaches with the pulsatile versus the continuous coverage make it difficult to measure, I think, between the two and compare the PK profiles. But what we can do is we can look at other long-acting CNP, both in preclinical models and the preclinical outcomes, and we can ask the question about sustained levels of CNP. That's what we've modeled from our cynomolgus monkey models.

我認為，脈衝覆蓋和連續覆蓋的根本不同方法使得兩者之間的測量和 PK 曲線的比較變得困難。但我們可以做的是，我們可以研究其他長效 CNP，包括臨床前模型和臨床前結果，我們可以詢問有關 CNP 持續程度的問題。這就是我們根據食蟹猴模型建模的。

And we believe that, again, if we can recapitulate what we've seen in those models against another long-acting more continuous coverage and activation of NPR2, we think that, again, by seeing multifold increases above what's been demonstrated so far, that opens the opportunity to test the hypothesis is more better. Hopefully, that answered your question.

我們相信，如果我們能夠重現這些模型中看到的情況，並與另一種長效、更持續的 NPR2 覆蓋和激活方法進行比較，我們認為，透過看到迄今為止已證明的數倍增長，這將為檢驗假設提供更好的機會。希望這能回答你的問題。

Mohit Bansal, Wells Fargo.

富國銀行的 Mohit Bansal。

This is [Joona] on for Mohit. I wanted to ask a question about BMN 351. In terms of the muscle dystrophin data expected in the second half, is that 10% dystrophin level the only goal that should inform the future course of action for this molecule? Or would you be looking at a bar for other parameters as well?

這是 [Joona] 為 Mohit 表演的。我想問一個關於 BMN 351 的問題。就預計下半年的肌肉營養不良蛋白數據而言，10% 的肌肉營養不良蛋白水平是否是指導該分子未來行動方向的唯一目標？或者您還會查看其他參數的長條圖嗎？

Thanks for the question. What we will have once patients have reached the six-month time point is we, of course, will have a totality of safety data and PK on a variety of species. And that includes not only the drug, but the muscle content of the drug because we're doing muscle biopsies. We'll also be able to look in the muscle at the skip product and the dystrophin. So all of those factors will be there.

謝謝你的提問。一旦患者達到六個月的時間點，我們當然會擁有各種物種的全部安全數據和 PK。這不僅包括藥物，還包括藥物的肌肉含量，因為我們正在進行肌肉活檢。我們也可以觀察肌肉中的跳躍產物和肌肉營養不良蛋白。所以所有這些因素都會存在。

We have actually released an illustrative example that was connected to our release today of a model that we put forward. And that model shows us that what we're going to see at the 25-, 26-week time point are dystrophin levels that when predicted out at steady state are going to rise two to threefold. And so they'll give us a line of sight whether that 10% at steady state will be achievable.

我們實際上已經發布了一個說明性範例，該範例與我們今天發布的我們提出的模型有關。該模型向我們展示了，在 25 週和 26 週的時間點，肌營養不良蛋白的水平在穩定狀態下預計會上升兩到三倍。因此他們會讓我們知道在穩定狀態下是否可以達到 10% 的目標。

We are also measuring in the study functional outcomes, which I think is the real question you're asking. The challenge, of course, with functional outcomes is you need to wait until, of course, to reach steady state of the drug. We're looking at North Star, we're looking at six-minute walk test. We're looking at strive velocity, [95C], all of those measures. We do anticipate that those will take longer than this initial first look.

我們也在研究中測量功能結果，我認為這是你真正想問的問題。當然，要獲得功能性結果，挑戰在於你需要等到藥物達到穩定狀態。我們正在觀察北極星，我們正在觀察六分鐘步行測試。我們正在研究努力速度、[95C] 以及所有這些措施。我們確實預計這些將比初次審視花費更長的時間。

I also want to remind the audience that this is the first data from our 6-milligram per kilogram cohort. We also have completely enrolled our 9-milligram per kilogram cohort. Again, as in a relay race, that's trailing behind in terms of time. But our goal here is to identify a molecule that not only has potent dystrophin induction, but also can, of course, be administered safely in a chronic fashion.

我還想提醒觀眾，這是我們每公斤 6 毫克隊列的第一批數據。我們也已完全招募了每公斤 9 毫克的隊列。再一次，就像接力賽一樣，從時間上來說，這是落後的。但我們的目標是找到一種不僅具有強效肌肉營養不良蛋白誘導作用，當然還可以以慢性方式安全給藥的分子。

Olivia Brayer, Cantor Fitzgerald.

奧莉維亞·布雷爾，費茲傑拉領唱者。

Greg, just wanted to clarify a comment you made earlier. Will we not see any level of Phase II data from other short stature indications until 2027? Or could we actually start to see some initial clinical characterization and maybe select patient groups, just to help derisk some of those new VOXZOGO indications? And then on the P&L, you guys are on track for over 20% EPS growth this year. Any comments on what kind of earnings power you think you could have as we get into the next few years?

格雷格，我只是想澄清一下你之前發表的評論。直到 2027 年我們才會看到其他身材矮小症的 II 期數據嗎？或者我們實際上可以開始看到一些初步的臨床特徵並選擇患者群體，只是為了幫助降低一些新的 VOXZOGO 適應症的風險？從損益表來看，今年你們的每股盈餘成長率可望超過 20%。您認為未來幾年您將擁有什麼樣的獲利能力？

Why don't I take a quick step just to clarify. With regard to the short stature conditions, obviously, I mean, the Dr. Dauber study with VOXZOGO continues and we do expect that that data will be updated over time. With regard to our own programs, what we're publicly commenting on is that we would have information to be able to initiate our Phase III study in 2027. It's possible that any time proximal to that, depending again on speed of enrollment and so forth, that we may have data.

我為什麼不快速採取一步措施來澄清呢？關於身材矮小的情況，顯然，我的意思是，Dauber 博士與 VOXZOGO 的研究仍在繼續，我們確實希望這些數據能夠隨著時間的推移而更新。關於我們自己的項目，我們公開表示，我們將擁有能夠在 2027 年啟動第三階段研究的資訊。有可能在接近該時間的任何時間，我們可能都會有數據，這又取決於註冊速度等等。

But we're not committing at least right now beyond the 2027 initiation of a Phase III. But clearly, we would need that data not only in-house, but we would be publicly presenting that data before we would initiate those Phase III studies.

但至少現在我們不會承諾在 2027 年啟動第三階段之後繼續進行。但顯然，我們不僅需要內部數據，在啟動第三階段研究之前，我們還需要公開展示這些數據。

And hi, Olivia. It's Brian on your profitability question. Thanks for that. Yes, we are pleased with this strong start to the year on the bottom line with the $1.13 of earnings per share growth. Again, we are expecting, while revenues are planning to increase in the second half of the year, we are also planning to increase investments in both R&D and SG&A over the course of the year. But by all means, we are confident in the full year EPS guidance with this strong start to the year.

你好，奧莉維亞。我是 Brian，來回答您的獲利能力問題。謝謝。是的，我們對今年每股收益成長 1.13 美元的強勁開局感到滿意。再次，我們預計，雖然下半年收入計劃增加，但我們也計劃在今年增加對研發和銷售、一般及行政費用的投資。但無論如何，鑑於今年開局強勁，我們對全年每股收益指引充滿信心。

And we do believe that will continue. I might -- in terms of earnings power, I would point you to our long-term guidance we remain confident in, at least today, excluding any potential impact of pharmaceutical tariffs, so whether it be the goal of $4 billion of revenue by 2027 or our 40% and growing non-GAAP operating margin target next year. We didn't give long-term earnings per share guidance, but you can do the math along the trajectory of our OpEx line-item goals over time and see that we are expecting significant earnings per share growth over the next several years and this year being at 22% at the midpoint of our guidance is the trajectory that we're talking about.

我們確實相信這種情況將會持續下去。我可能會——就盈利能力而言，我會指出我們仍然有信心的長期指導，至少在今天，不包括藥品關稅的任何潛在影響，所以無論是到 2027 年實現 40 億美元的收入目標，還是明年 40% 且不斷增長的非 GAAP 營業利潤率目標。我們沒有給出長期每股收益指引，但您可以沿著我們的營運支出項目目標隨時間的變化軌跡進行計算，就會發現我們預計未來幾年每股收益將大幅增長，而今年的每股收益增長率為 22%，處於指引的中點，這就是我們所談論的軌跡。

We have reached the end of the Q&A session. Our final question today will come from Vikram Purohit, Morgan Stanley.

問答環節已結束。今天的最後一個問題來自摩根士丹利的 Vikram Purohit。

Thanks for fitting me in. We just had two quick clarification questions on BMN 333. Apologies if these topics were discussed and we missed it, but just to make sure we understand. So for the pivotal program plan to initiate in 2026, would the bar for approval necessarily be superior efficacy versus VOXZOGO through the comparative effectiveness study that you're planning to run? And then secondly, could you talk a bit about your plans to seek approval and define a plan forward ex US as well?

謝謝你幫我安排。我們剛剛對 BMN 333 提出了兩個快速澄清問題。如果我們錯過了討論這些主題的機會，我們深感抱歉，但這只是為了確保我們理解。那麼，對於 2026 年啟動的關鍵計劃，透過您計劃進行的比較有效性研究，批准標準是否一定是比 VOXZOGO 具有更優異的療效？其次，您能否談談您尋求批准的計劃以及製定美國以外的未來計劃？

Yes. Thanks for the question. Just to clarify, the announcement today, again, was that we had reached agreement with the FDA, and we're continuing to work with regulators around the globe. The study that we referred to that would initiate in 2026 is a combined Phase II/III study. And in that regard, we are doing dose ranging as well as the final comparative effectiveness versus VOXZOGO, and we would be looking for a superior outcome with regard to the primary endpoint in that study versus the controller.

是的。謝謝你的提問。需要澄清的是，今天再次宣布，我們已與 FDA 達成協議，並且我們將繼續與全球監管機構合作。我們所提到的將於 2026 年啟動的研究是一項 II/III 期綜合研究。在這方面，我們正在進行劑量範圍以及與 VOXZOGO 的最終比較有效性，我們希望在研究的主要終點方面獲得優於控制器的結果。

And everyone, at this time, there are no further questions. I'd like to hand the conference back to the CEO for any additional or closing remarks.

各位，目前，沒有其他問題了。我想將會議交還給首席執行官，以便他發表任何補充或結束語。

Thank you, operator, and thank you all for joining us today. As we described, our first quarter performance highlights the fundamental value of our transformative medicines and the strength of our business, paving the way for record performance in full year 2025. In the face of external dynamics that are creating uncertainty across a number of areas, we think we are well positioned.

謝謝接線員，也謝謝大家今天加入我們。正如我們所描述的，我們的第一季業績凸顯了我們變革性藥物的根本價值和業務實力，為 2025 年全年創紀錄的業績鋪平了道路。面對在多個領域造成不確定性的外部動態，我們認為我們已做好準備。

We remain laser-focused on what we can control, investing in the expansion of internal and external innovation, leveraging our extensive global revenue base and our commercialization capabilities, and most importantly, continuing to deliver increasing value creation to all of our stakeholders in 2025 and beyond. We thank you for your attention. We look forward to speaking with you soon.

我們始終專注於我們能夠控制的事情，投資於內部和外部創新的擴展，利用我們廣泛的全球收入基礎和商業化能力，最重要的是，在 2025 年及以後繼續為所有利益相關者創造越來越多的價值。感謝您的關注。我們期待很快與您交談。

And once again, everyone, that does conclude today's conference. We would like to thank you all for your participation today. You may now disconnect.

各位，今天的會議到此結束。我們感謝大家今天的參與。您現在可以斷開連線。