BioMarin Pharmaceutical Inc (BMRN) 2023 Q2 法說會逐字稿

Thank you for joining BioMarin's second quarterly results conference call. Hosting today's call from BioMarin is Traci McCarty, Head of Investor Relations at BioMarin. Please go ahead, Traci.

感謝您參加 BioMarin 第二季度業績電話會議。 BioMarin 投資者關係主管 Traci McCarty 主持了今天的 BioMarin 電話會議。請繼續，特蕾西。

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

謝謝 Jaicy，也謝謝大家今天加入我們。提醒您，本非機密演示文稿包含有關 BioMarin Pharmaceutical Inc. 業務前景的前瞻性陳述，包括對 BioMarin 的財務業績、商業產品以及治療研究和開發不同領域的潛在未來產品的預期。結果可能會存在重大差異，具體取決於 BioMarin 產品計劃的進展、監管機構的行動、資本的可用性、製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中詳細說明的因素，例如 10 -Qs、10-K 和 8-K 報告。

On the call from BioMarin's management team today are JJ Bienaime, Chairman and Chief Executive Officer; Jeff Ajer, Executive Vice President, Chief Commercial Officer; Henry Fuchs, President, Worldwide Research and Development; Greg Guyer, Executive Vice President, Commercial, Chief Technical Officer; Brian Mueller, Executive Vice President and Chief Financial Officer.

BioMarin 管理團隊今天接聽了董事長兼首席執行官 JJ Bienaime 的電話； Jeff Ajer，執行副總裁兼首席商務官； Henry Fuchs，全球研發總裁； Greg Guyer，商務執行副總裁、首席技術官；布萊恩·穆勒 (Brian Mueller)，執行副總裁兼首席財務官。

I will now turn the call over to BioMarin's Chairman and CEO, JJ Bienaime.

我現在將把電話轉給 BioMarin 董事長兼首席執行官 JJ Bienaime。

Thank you, Traci, and good afternoon, everyone. Thank you for joining us today on this call. We were very pleased with our progress in the second quarter as more families around the world get access to Voxzogo and the highly anticipated FDA approval of Roctavian was received. The achievement of these 2 milestones are key components of our growth plans, including continued Voxzogo expansion and Roctavian launch execution.

謝謝你，特雷西，大家下午好。感謝您今天參加我們的電話會議。我們對第二季度的進展感到非常滿意，因為世界各地越來越多的家庭可以使用 Voxzogo，並且 Roctavian 獲得了 FDA 高度期待的批准。這兩個里程碑的實現是我們增長計劃的關鍵組成部分，包括持續的 Voxzogo 擴張和 Roctavian 的發布執行。

Record revenues of approximately $1.2 billion in the first half of the year represented 13% year-over-year growth and 16% growth, excluding KUVAN. Our commitment to profitability was demonstrated again this quarter, and we were pleased to deliver $56 million in GAAP net income as a result of strong product demand. With Q2 total revenues coming in at $595 million, including $113 million in Voxzogo revenues, we are on a path to achieving our 2023 objectives of double-digit revenue growth and significant operating leverage. This is expected to drive more than 30% growth in bottom line profitability in 2023 as communicated earlier this year.

上半年營收約 12 億美元，創歷史新高，同比增長 13%，不包括 KUVAN 則增長 16%。我們對盈利的承諾在本季度再次得到體現，由於強勁的產品需求，我們很高興實現了 5600 萬美元的 GAAP 淨利潤。第二季度總收入為 5.95 億美元，其中 Voxzogo 收入為 1.13 億美元，我們正在實現 2023 年兩位數收入增長和顯著運營槓桿的目標。正如今年早些時候所傳達的那樣，預計這將推動 2023 年淨利潤增長 30% 以上。

We were very pleased to have received FDA's approval of Roctavian in the quarter as we believe the demonstrated clinical benefits of this onetime gene therapy has transformative potential for those living with severe hemophilia A and eligible for treatment.

我們很高興在本季度獲得 FDA 對 Roctavian 的批准，因為我們相信這種一次性基因療法已證實的臨床益處對於那些患有嚴重 A 型血友病並有資格接受治療的患者俱有變革潛力。

With combined U.S. and European addressable patient population of nearly 6,000 patients, we are optimistic that Roctavian will become the treatment of choice for those seeking an alternative to chronic therapy. The commercial team moved quickly to activate the first phase of launch following FDA's approval, and we have been encouraged by the early signals of interest in Roctavian in the United States. We have also made good progress in Germany and other European countries during the quarter, and Jeff will provide more launch details in a moment.

美國和歐洲的可尋址患者群體總計接近 6,000 名患者，我們樂觀地認為 Roctavian 將成為那些尋求慢性治療替代方案的患者的首選治療方法。在 FDA 批准後，商業團隊迅速採取行動啟動第一階段的上市，我們對美國對 Roctavian 的早期興趣信號感到鼓舞。本季度我們在德國和其他歐洲國家也取得了良好進展，傑夫將立即提供更多發布細節。

Turning to Voxzogo. We continue to be impressed by the cadence of uptake worldwide. As a result of continued strong demand, we are raising full year Voxzogo guidance for the second time this year to between $400 million and $440 million, representing a significant increase from our initial guidance in February of between $330 million and $380 million. Jeff will provide additional detail on our Voxzogo guidance in a moment.

轉向沃克斯佐戈。全球範圍內的採用節奏仍然給我們留下了深刻的印象。由於需求持續強勁，我們今年第二次將 Voxzogo 全年指導方針上調至 4 億至 4.4 億美元之間，較 2 月份 3.3 億至 3.8 億美元之間的初步指導大幅增加。 Jeff 稍後將提供有關我們的 Voxzogo 指南的更多詳細信息。

Building on the significant demand for Voxzogo for the treatment of achondroplasia, we are pleased to have announced today and like to begin our pivotal program with Voxzogo for the treatment of hypochondroplasia. With over 7 years of efficacy and safety data from our clinical program and nearly 2 years of commercial experience in achondroplasia, we view Voxzogo as highly derisked and now on the fast track in a potential second new underserved patient population. Hank will provide more details in a moment, but suffice it to say we are rapidly executing on our expansion plans with Voxzogo.

鑑於對 Voxzogo 治療軟骨發育不全的巨大需求，我們很高興今天宣布並希望開始使用 Voxzogo 治療軟骨發育不全的關鍵計劃。憑藉我們臨床項目超過 7 年的療效和安全性數據以及近 2 年的軟骨發育不全商業經驗，我們認為 Voxzogo 風險很高，目前在潛在的第二個新的服務不足的患者群體中處於快速發展階段。 Hank 稍後將提供更多細節，但足以說明我們正在快速執行 Voxzogo 的擴張計劃。

Certainly, we are very pleased with BioMarin's performance in the second quarter and year-to-date. The global demand for Voxzogo continues to drive record revenue and margin expansion, supporting our confidence that we will potentially be -- it will be our first blockbuster product.

當然，我們對 BioMarin 第二季度和年初至今的表現非常滿意。全球對 Voxzogo 的需求繼續推動創紀錄的收入和利潤增長，這支持了我們的信心，即這將是我們的第一個重磅產品。

With Roctavian, we're excited about the opportunity ahead and remain focused on launch execution both in the United States and Europe. We believe our ability to raise awareness of Roctavian along patients and physicians in the U.S. through a direct outreach to the hemophilia A community will result in meaningful demand over the coming quarters.

對於 Roctavian，我們對未來的機會感到興奮，並繼續專注於在美國和歐洲的發布執行。我們相信，我們有能力通過直接接觸 A 型血友病社區來提高美國患者和醫生對 Roctavian 的認識，這將在未來幾個季度產生有意義的需求。

Thank you for your continued support. And I now will turn the call over to Jeff to discuss the commercial business update. Jeff?

感謝您一如既往的支持。我現在將把電話轉給傑夫，討論商業業務的最新情況。傑夫？

Thank you, JJ. I'm very pleased with our commercial performance in the second quarter, resulting in $595 million in total revenues and representing 12% growth year-over-year including KUVAN and 14% growth excluding KUVAN. Contributions from our enzyme products in the quarter keep us on track to deliver full year 2023 guidance for this franchise, as well as provide significant contributions to BioMarin's full year 2023 total revenues.

謝謝你，傑傑。我對我們第二季度的商業表現非常滿意，總收入達到 5.95 億美元，包括 KUVAN 在內同比增長 12%，不包括 KUVAN 則同比增長 14%。本季度酶產品的貢獻使我們能夠為該特許經營業務提供 2023 年全年指導，並為 BioMarin 2023 年全年總收入做出重大貢獻。

Turning to Voxzogo. Today, we increased full year guidance again as new patient penetration continues to exceed our aggressive expectations. As noted in the press release, today, we once again raised full year Voxzogo revenues guidance to between $400 million and $440 million, representing 150% year-over-year growth at the midpoint of guidance.

轉向沃克斯佐戈。今天，隨著新患者滲透率繼續超出我們的積極預期，我們再次提高了全年指導。正如新聞稿中所指出的，今天，我們再次將 Voxzogo 全年收入指引上調至 4 億至 4.4 億美元之間，相當於指引中點的同比增長 150%。

Appreciating that the run rate for the remainder of the year may seem muted based on Voxzogo revenues of $201 million in the first half of the year, we note that we are managing temporarily tight supply into 2024. We are closely managing new growth, including limiting inventory stocking to ensure that we achieve our main goal, which is to ensure that patients maintain continuity of Voxzogo.

鑑於 Voxzogo 上半年收入為 2.01 億美元，今年剩餘時間的運行率可能會顯得平淡，我們注意到我們正在管理 2024 年暫時緊張的供應。我們正在密切管理新的增長，包括限制庫存備貨以確保我們實現我們的主要目標，即確保患者保持 Voxzogo 的連續性。

Importantly, while we are focusing on inventory levels and new patient starts, our supply plan provides for hundreds of new patient starts in the second half of this year. We do have ample drug substance on hand, which we manufacture at our Nevada facility and have sufficient capacity to meet all future demands for achondroplasia and other possible indications.

重要的是，雖然我們關注庫存水平和新患者啟動情況，但我們的供應計劃為今年下半年的數百名新患者啟動提供了保障。我們手頭上確實有充足的原料藥，我們在內華達州的工廠生產這些原料藥，並且有足夠的能力滿足未來對軟骨發育不全和其他可能適應症的所有需求。

We have secured additional capacity at our fill-finish CMO, which is the constrained element of the process. These accelerated steps will ensure that we have ample supply to exceed full year 2024 consensus currently at $597 million on FactSet and support growth beyond 2024.

我們已經確保了填充完成 CMO 的額外產能，這是該流程的受限要素。這些加速措施將確保我們有充足的供應，以超過 FactSet 目前 5.97 億美元的 2024 年全年共識，並支持 2024 年以後的增長。

At the end of the second quarter, more than 2,000 children with achondroplasia in 36 different markets were being treated with Voxzogo. Uptake to date represents 12% penetration of indicated patients in BioMarin's commercial footprint, highlighting the significant growth potential remaining.

截至第二季度末，36 個不同市場的 2,000 多名軟骨發育不全兒童正在接受 Voxzogo 治療。迄今為止，BioMarin 商業足跡中指定患者的使用率已達 12%，凸顯了剩餘的巨大增長潛力。

Turning now to Roctavian. We've been very pleased with U.S. launch progress since receiving FDA approval on June 29. Following approval, the team immediately began the outreach campaign, educating stakeholders, including patients, hemophilia treatment centers or HTCs and payers on the value of Roctavian. In the 4 weeks since approval, we've been pleased with the increasing inflow of patient consent forms, the number of executed or in-process warranty agreements and the utility of our executed group purchasing agreement contract that we expect will facilitate access and uptake of Roctavian at hemophilia treatment centers across the U.S.

現在轉向羅克塔維安。自 6 月 29 日獲得 FDA 批准以來，我們對在美國的上市進展感到非常滿意。獲得批准後，團隊立即開始了外展活動，向利益相關者（包括患者、血友病治療中心或 HTC 和付款人）宣傳 Roctavian 的價值。在批准後的 4 週內，我們對患者同意書的流入不斷增加、已簽署或正在進行的保修協議的數量以及已簽署的團體採購協議合同的效用感到滿意，我們預計這些合同將有助於訪問和採用羅克塔維安在美國各地的血友病治療中心

There are many commercial activities ongoing to facilitate access to Roctavian. We are currently in process of working with the largest, most capable hemophilia treatment centers' on-site readiness. On the payer side, our U.S. market access team has been actively engaging with payers to facilitate patient access and the issuance of coverage policies. In advance of coverage policies being issued by payers and once commercial Roctavian is available in the U.S., we have the ability to get approval for individual patients through the medical exception process.

為了方便訪問 Roctavian，正在進行許多商業活動。我們目前正在與最大、最有能力的血友病治療中心合作，做好現場準備。在付款人方面，我們的美國市場准入團隊一直在積極與付款人接觸，以促進患者准入和承保政策的發布。在付款人簽發承保保單之前，一旦商業 Roctavian 在美國上市，我們就有能力通過醫療例外流程為個別患者獲得批准。

In summary, in the U.S., we are actively promoting Roctavian to the hemophilia community, and the sales force has been activated in all key regions. We expect labeled commercial Roctavian to be available to ship to pharmacies in August and look forward to updating you of our progress over the coming months.

綜上所述，在美國，我們正在積極向血友病人群推廣 Roctavian，銷售隊伍已在各個重點地區啟動。我們預計貼有標籤的商業 Roctavian 將於 8 月份運往藥店，並期待在未來幾個月向您通報我們的最新進展。

As we stated on our June approval call, we expect it could take from 2 to 5 months to complete the steps necessary before treatment with Roctavian, depending on our patients' location, insurer, cadence of regularly scheduled visits with the HTCs and completion of eligibility testing.

正如我們在 6 月份的批准電話中所述，我們預計可能需要 2 至 5 個月的時間才能完成 Roctavian 治療之前的必要步驟，具體取決於患者所在位置、保險公司、定期 HTC 就診的節奏以及完成資格的情況測試。

Moving briefly to Roctavian United States and Europe, we continue to make good progress. In Germany, new AAV5 antibody tests in Germany continue to come through, resulting in a robust funnel of patients preparing for potential treatment with Roctavian. While final federal pricing negotiations are ongoing, reimbursement for patients treated with Roctavian is possible under named patient authorizations through individual insurers. Those sales would be subject to the final price once it has been established.

短暫前往羅克塔維安美國和歐洲，我們繼續取得良好進展。在德國，新的 AAV5 抗體測試不斷進行，導致大量患者準備接受 Roctavian 的潛在治療。雖然最終的聯邦定價談判正在進行中，但根據個別保險公司的指定患者授權，可以對接受 Roctavian 治療的患者進行報銷。這些銷售將取決於最終價格確定後的情況。

In Italy and France, we are also making good progress. Our application seeking price and reimbursement approvals as well as other launch preparation activities are moving ahead in both countries, where we expect negotiations to conclude by Q4 of this year. We continue to be encouraged by early interest in Roctavian and other markets, including Argentina and Saudi Arabia, where we have the potential to provide access to Roctavian through named patient authorizations. Taken together, we are pleased with the progress we are seeing in markets outside of the United States.

在意大利和法國，我們也取得了良好進展。我們尋求價格和報銷批准的申請以及其他發射準備活動正在這兩個國家取得進展，我們預計談判將在今年第四季度結束。我們繼續對 Roctavian 和其他市場（包括阿根廷和沙特阿拉伯）的早期興趣感到鼓舞，我們有潛力通過指定患者授權提供 Roctavian 的使用權。總的來說，我們對美國以外市場所取得的進展感到高興。

Briefly on full year 2023 Roctavian guidance. We maintain our current full year 2023 guidance of between $50 million to $150 million. Appreciating that we are at the start of launching a truly pioneering therapy, which has required significant effort to support novel reimbursement arrangements, as well as training for those providing Roctavian treatment and follow-up, we believe there are a variety of potential outcomes over the next several months.

簡要介紹 Roctavian 2023 年全年指導。我們維持當前 2023 年全年指引為 5000 萬至 1.5 億美元之間。我們意識到我們正處於啟動一項真正開創性療法的開端，該療法需要付出巨大努力來支持新的報銷安排，以及對提供 Roctavian 治療和隨訪的人員進行培訓，我們相信在這一過程中會有多種潛在的結果接下來的幾個月。

Our confidence in the guidance range is supported by ongoing progress in Europe, requests from patients for CDx testing and treatment, the inflow of patient consent forms and warranties in the U.S., and feedback from physicians globally as well as the onetime nature of both Roctavian treatment and reimbursement. For perspective, the treatment of slightly more than 50 U.S. patients achieves the midpoint of current guidance. So stay tuned over the coming months as we track global launch progress.

我們對指導範圍的信心得到了歐洲持續進展、患者對 CDx 檢測和治療的要求、美國患者同意書和保證的流入、全球醫生的反饋以及 Roctavian 治療的一次性性質的支持。和報銷。從長遠來看，略多於 50 名美國患者的治療達到了當前指導的中點。因此，請在接下來的幾個月中繼續關注我們跟踪全球發布進展的情況。

In conclusion, at the midpoint of 2023, we are on track to achieve full year total revenue guidance. The unique onetime treatment and reimbursement profile of Roctavian lends itself to contributing meaningfully during the second half of the year. Voxzogo continues to exceed expectations, resulting in 2 guidance increases so far this year. The start of our new pivotal program with Voxzogo for the treatment of hypochondroplasia opens the possibility of a new indication opportunity for a marketed product. These opportunities are now layered on top of BioMarin's established base business that delivers nearly $2 billion annually and growing. Taken together, we are well positioned to achieve financial growth and profitability goals outlined earlier this year.

總之，到 2023 年中期，我們有望實現全年總收入指引。 Roctavian 獨特的一次性治療和報銷概況有助於在今年下半年做出有意義的貢獻。 Voxzogo 繼續超出預期，導致今年迄今為止指導值上調了 2 次。我們與 Voxzogo 治療軟骨發育不全的新關鍵計劃的啟動為上市產品帶來了新的適應症機會。這些機會現在位於 BioMarin 既定的基礎業務之上，該業務每年創造近 20 億美元的收入，並且還在不斷增長。總而言之，我們完全有能力實現今年早些時候提出的財務增長和盈利目標。

Thank you for your attention. And I will now turn the call over to Hank to provide an R&D update. Hank?

感謝您的關注。我現在將把電話轉給漢克，以提供研發最新信息。漢克？

Thanks, Jeff, and thank you all for joining us today. Echoing JJ and Jeff's enthusiasm for the June 29 Food and Drug Administration approval of Roctavian, we are extremely gratified that people in the United States living with severe hemophilia A have access to this innovative therapy. Our goal with each of BioMarin's therapeutic interventions is improving health outcomes for people with genetic conditions, and we believe Roctavian clearly achieves that goal.

謝謝杰夫，也感謝大家今天加入我們。與 JJ 和 Jeff 對 6 月 29 日 FDA 批准 Roctavian 的熱情一樣，我們非常高興美國患有嚴重 A 型血友病的人們能夠獲得這種創新療法。我們對 BioMarin 的每項治療干預措施的目標是改善遺傳性疾病患者的健康結果，我們相信 Roctavian 顯然實現了這一目標。

As we have stated previously, we believe Voxzogo has the potential to treat a variety of genetic statural conditions, many of which represent significant unmet need. As JJ mentioned, we have solidified our plans to begin with the pivotal program with Voxzogo for the treatment of hypochondroplasia. We estimate the patient population in hypochondroplasia across BioMarin's global territories to be approximately 15,000 individuals and expect the full spectrum of disease to be elucidated over the course of the study.

正如我們之前所說，我們相信 Voxzogo 具有治療多種遺傳狀況的潛力，其中許多代表了未滿足的重大需求。正如 JJ 提到的，我們已經鞏固了我們的計劃，從 Voxzogo 治療軟骨發育不全的關鍵項目開始。我們估計 BioMarin 全球範圍內的軟骨發育不全患者人數約為 15,000 人，並期望在研究過程中闡明全部疾病譜。

As a reminder, hypochondroplasia is a genetic skeletal dysplasia characterized by small stature and disproportionately short arms, legs, hands and feet. As Dr. Andrew Dauber, [whom] BioMarin is supporting to run the Phase II study of Voxzogo in a multitude of genetic statural conditions has educated us, for decades, doctors had only one tool to improve outcomes in patients with skeletal diseases, and it does not work well outside of growth hormone deficiency. As is typical in BioMarin, we look forward to ushering in a new era in improving health outcomes for children with severe impairment and growth now beyond achondroplasia.

提醒一下，軟骨發育不良是一種遺傳性骨骼發育不良，其特徵是身材矮小，手臂、腿、手和腳不成比例地短。 BioMarin 支持在多種遺傳狀況下開展 Voxzogo II 期研究的 Andrew Dauber 博士告訴我們，幾十年來，醫生只有一種工具來改善骨骼疾病患者的治療結果，而它在生長激素缺乏的情況下效果不佳。正如 BioMarin 的典型做法一樣，我們期待開創一個新時代，改善患有嚴重損傷和生長發育超出軟骨發育不全的兒童的健康結果。

Following our interactions with the FDA and based on the emerging data set from Dr. Dauber's study, we aligned on a study design to test Voxzogo in these new indications. Supported by our extensive clinical development program in achondroplasia and profile of Voxzogo as a natural regulator of bone growth, we are pleased to be moving directly into a pivotal program in hypochondroplasia. We plan to begin the 6-month observation of the study later -- arm of the study later this year, followed by a 52-week randomized, double-blind, placebo-controlled phase of the 80-participant clinical trial.

在與 FDA 進行互動後，並根據 Dauber 博士研究中的新數據集，我們調整了一項研究設計，以測試 Voxzogo 在這些新適應症中的應用。在我們廣泛的軟骨發育不全臨床開發項目和 Voxzogo 作為骨骼生長天然調節劑的支持下，我們很高興直接進入軟骨發育不全的關鍵項目。我們計劃在今年晚些時候開始對該研究進行為期 6 個月的觀察——該研究的一部分，然後是為期 52 週的隨機、雙盲、安慰劑對照階段的 80 名參與者的臨床試驗。

Based on the enthusiasm we have seen with Voxzogo for the treatment of achondroplasia, we're excited to get started on the first potential treatment option for children with hypochydroplasia.

基於我們對 Voxzogo 治療軟骨發育不全的熱情，我們很高興開始為患有軟骨發育不全的兒童提供第一個潛在的治療選擇。

Briefly, on the earlier-stage pipeline, we've been working to put together in an interesting and informative update across our pipeline programs for our upcoming R&D Day on September 12. This includes our 5 publicly disclosed product candidates as well as other new updates. The agenda includes BMN 255 for hyperoxaluria in chronic liver disease, BMN 331 gene therapy for hereditary angioedema, BMN 349 for alpha-1 antitrypsin deficiency, BMN 351 for Duchenne muscular dystrophy and BMN 293 for myosin-binding C3 protein deficiency causing hypertrophic cardiomyopathy. And some fireside chats with key opinion leaders or key areas of our therapeutic focus for BioMarin will be an important and interesting part of the R&D Day. We look forward to sharing an update on what's been happening in the earlier-stage pipeline, and we hope that you'll tune in to learn more about next potential commercial product candidates.

簡而言之，在早期階段的管道中，我們一直在努力為即將到來的 9 月 12 日研發日，對我們的管道計劃進行有趣且信息豐富的更新。這包括我們公開披露的 5 個候選產品以及其他新更新。議程包括治療慢性肝病高草酸尿症的 BMN 255、治療遺傳性血管性水腫的 BMN 331 基因治療、治療 α-1 抗胰蛋白酶缺乏症的 BMN 349、治療杜氏肌營養不良症的 BMN 351 和治療導致肥厚性心肌病的肌球蛋白結合 C3 蛋白缺乏症的 BMN 293。與主要意見領袖或我們 BioMarin 治療重點的關鍵領域進行一些爐邊談話將是研發日的一個重要且有趣的部分。我們期待分享早期管道中發生的最新情況，並希望您能夠收聽以了解有關下一個潛在商業候選產品的更多信息。

Thanks for your support. And I'll now turn the call over to Brian to update financial results in the quarter. Over to you, Brian.

感謝您的支持。我現在將電話轉給布萊恩，更新本季度的財務業績。交給你了，布萊恩。

Thank you, Hank. Please refer to today's press release summarizing our financial results for full details on the second quarter of 2023. Since JJ and Jeff spoke to our revenue performance for the quarter and future revenue outlook, I'll make just a few more revenue comments, then we'll focus on the remainder of our P&L and other key financial updates this quarter. As usual, all results will be available in our upcoming Form 10-Q, which we are on track to file over the next couple of days.

謝謝你，漢克。請參閱今天總結我們財務業績的新聞稿，了解 2023 年第二季度的完整詳細信息。由於 JJ 和 Jeff 談到了我們本季度的收入表現和未來的收入前景，我將再做一些收入評論，然後我們我們將重點關注本季度損益表的其餘部分以及其他關鍵財務更新。與往常一樣，所有結果都將在我們即將發布的 10-Q 表格中提供，我們將在接下來的幾天內提交該表格。

As we have previously noted, we viewed last year as a transformative year of BioMarin, laying the foundation of our growth strategy driven by Voxzogo, approval of Roctavian in the EU, double-digit revenue growth and our important milestone of sustainable full year GAAP profitability in 2022. As we close the first half of 2023, we're pleased to build on that foundation with the approval of Roctavian in the U.S. and strong first half financial performance that aligns to our long-term objectives of continued revenue growth and P&L leverage.

正如我們之前指出的，我們認為去年是 BioMarin 變革的一年，為我們由 Voxzogo 驅動的增長戰略奠定了基礎， Roctavian 在歐盟獲得批准，兩位數的收入增長以及我們可持續全年 GAAP 盈利能力的重要里程碑2022 年。隨著 2023 年上半年的結束，我們很高興在此基礎上再接再厲，獲得 Roctavian 在美國的批准，並且上半年強勁的財務業績符合我們持續收入增長和損益槓桿的長期目標。

BioMarin's $595 million of total revenue in the second quarter of 2023 is an increase of 12% compared to the second quarter of 2022. Regarding our revenue outlook, for the rest of 2023, we continue to anticipate strong double-digit growth of 16%, at the midpoint of our reaffirmed total revenue guidance.

BioMarin 2023 年第二季度的總收入為 5.95 億美元，較 2022 年第二季度增長 12%。關於我們的收入前景，對於 2023 年剩餘時間，我們繼續預計 16% 的強勁兩位數增長，在我們重申的總收入指導的中點。

As Jeff mentioned earlier, we are pleased with our first half performance of Voxzogo. And given the first half revenue has come in over $200 million, we felt it appropriate to note that the low end of our prior guidance is no longer in line with our expectations. So with that in mind, we have provided an updated view for the year, raising guidance slightly to $400 million to $440 million.

正如 Jeff 之前提到的，我們對 Voxzogo 上半場的表現感到滿意。鑑於上半年收入已超過 2 億美元，我們認為有必要指出我們之前指導的下限不再符合我們的預期。因此，考慮到這一點，我們提供了今年的最新觀點，將指導小幅上調至 4 億至 4.4 億美元。

Moving now to revenue. Q2 2023 gross margin was 78.5%, which is an improvement of 1.6% as compared to the second quarter of 2022. We are pleased with our gross margin performance over the first half of 2023 as it reflects our fundamental objective to improve this metric through cost efficiencies and favorable product mix.

現在轉向收入。 2023 年第二季度的毛利率為 78.5%，比 2022 年第二季度提高了 1.6%。我們對 2023 年上半年的毛利率表現感到滿意，因為它反映了我們通過成本改善這一指標的基本目標效率和有利的產品組合。

R&D expense in Q2 2023 of $177 million and SG&A expense of $215 million grew 12% and 9% versus Q2 2022, respectively, and in line with our goal to grow expense base slower than revenue. While we expect operating expense growth on a full year basis to align to that goal, we do anticipate a second half acceleration of expenses as we continue to progress our R&D pipeline, including the new Phase III study announced today for hypochondroplasia, and investments in the Roctavian and Voxzogo launches.

2023 年第二季度的研發費用為 1.77 億美元，SG&A 費用為 2.15 億美元，與 2022 年第二季度相比分別增長了 12% 和 9%，這符合我們使費用基礎增長慢於收入的目標。雖然我們預計全年運營費用增長將與這一目標保持一致，但我們確實預計下半年費用將加速，因為我們繼續推進我們的研發管道，包括今天宣布的針對軟骨發育不全的新三期研究，以及對Roctavian 和 Voxzogo 推出。

On the bottom line, we continue to deliver on our commitment to profitability with $56 million of GAAP net income in Q2 2023 and $105 million of non-GAAP income. This positions us to achieve our stated objective of sustained and growing full year GAAP profitability going forward.

總而言之，我們繼續履行盈利承諾，2023 年第二季度 GAAP 淨利潤為 5600 萬美元，非 GAAP 收入為 1.05 億美元。這使我們能夠實現我們既定的目標，即未來全年 GAAP 盈利能力持續增長。

Today, we also updated our 2023 GAAP and non-GAAP income guidance to $165 million to $215 million and $370 million to $420 million, respectively. Similar to our Voxzogo revenue guidance adjustment, our updated outlook for the bottom line reflects our strong performance in the first half of the year and continued revenue growth expectations in the back half of 2023. At the midpoint, we expect more than 30% of net income growth, which represents meaningful leverage versus revenue and is in line with our financial transformation goal.

今天，我們還將 2023 年 GAAP 和非 GAAP 收入指引分別更新為 1.65 億至 2.15 億美元和 3.7 億至 4.2 億美元。與我們的 Voxzogo 收入指導調整類似，我們更新的淨利潤前景反映了我們上半年的強勁表現以及 2023 年下半年收入持續增長的預期。在中點，我們預計淨收入將超過 30%收入增長，代表著有意義的槓桿與收入的關係，並且符合我們的財務轉型目標。

In closing, we are on track to meet our objectives for 2023 and beyond. The recent approval of Roctavian in the U.S., coupled with the strong foundation in place, including the successful Voxzogo launch, will further enable our ability to drive revenue growth, expand profitability and generate meaningful cash flows over the course of the next several years.

最後，我們有望實現 2023 年及以後的目標。 Roctavian 最近在美國獲得批准，加上已經奠定的堅實基礎，包括 Voxzogo 的成功推出，將進一步使我們有能力在未來幾年內推動收入增長、擴大盈利能力並產生有意義的現金流。

Thank you for your attention. And we'll now open up the call to your questions. Operator?

感謝您的關注。現在我們將開始電話詢問您的問題。操作員？

(Operator Instructions) Your first question comes from the line of Akash Tewari from Jefferies.

（操作員說明）您的第一個問題來自 Jefferies 的 Akash Tewari。

So just any update on the 300 patients you've previously had interactions with regarding Roctavian in the U.S. It sounds like you won't get commercial product into the distribution centers until late August. But I think you've previously mentioned you're going to see some leading indicators in terms of patients who've actually been treated with the companion diagnostic or have actually gone to a treatment center of excellence. So I'd love any update on that number.

因此，只要是您之前在美國與 Roctavian 進行過互動的 300 名患者的任何更新，聽起來您要到 8 月底才能將商業產品送入配送中心。但我認為您之前提到過，您將看到一些關於實際接受伴隨診斷治療或實際前往卓越治療中心的患者的領先指標。所以我希望了解該數字的任何更新。

And then, I guess, number two, on hypochondroplasia data. Can you comment a bit on why the FDA wouldn't require 2 years of Phase III data for Voxzogo like they did in hyperchondroplasia? And also maybe what time lines would be for Noonan syndrome, right? I think you have about 5 patients' worth of data right now. Should we expect that you would need about 25 patients' worth of data at the 15-microgram dose in Noonan to be supported for Phase II approval there?

然後，我想，第二點是關於軟骨發育不全的數據。您能否評論一下為什麼 FDA 不像軟骨發育過度症那樣要求 Voxzogo 提供 2 年的 III 期數據？也許努南綜合症的時間表是什麼，對吧？我認為您現在擁有大約 5 個患者的數據。我們是否應該預計您需要 Noonan 15 微克劑量的大約 25 名患者的數據來支持那裡的 II 期批准？

Jeff, do you want to start with the first question and then Hank?

傑夫，你想從第一個問題開始，然後是漢克嗎？

Yes. Akash, I'll start with your first question. It's absolutely the case that we started with the U.S. launch with an estimated 300 qualified patient leads. So these are individuals that had been in touch with BioMarin through either one of our digital properties or an in-person engagement and had opted into further information. As noted on our approval call a month ago, that list of 300 is top priority for getting back to in different ways, digitally and through our sales force. And I can assure you that the team has been processing those leads in the last month and actively.

是的。阿卡什，我將從你的第一個問題開始。情況確實如此，我們從美國推出時就擁有估計 300 名合格的患者線索。這些人是通過我們的數字資產或面對面接觸與 BioMarin 取得聯繫並選擇了解更多信息的個人。正如一個月前我們在批准電話會議上所指出的那樣，這 300 名名單是通過不同方式（數字方式和通過我們的銷售團隊）返回的首要任務。我可以向您保證，團隊在上個月一直在積極處理這些潛在客戶。

And as you noted, we expect and in fact are seeing small pieces of signals of demand falling into place from responses to those lead engagements to patient consent forms coming in. So things are looking really encouraging on that front.

正如您所指出的，我們預計並且事實上正在看到從對這些主要參與的反應到患者同意書的出現，一小部分需求信號正在落實到位。因此，在這方面，事情看起來非常令人鼓舞。

And maybe with that, I'd turn it over to Hank on hyperchon and Noonan questions.

也許這樣，我就會把關於 hyperchon 和 Noonan 的問題交給漢克。

Yes. Thanks, Jeff, and thanks, Akash, for the inquiry. In terms of the duration of the hypochondroplasia in contrast to achondroplasia in which the FDA has been very interested in 2 years of data, we've lined up with the FDA that a 1-year study would be support -- sufficient for spot registration. And I think that's driven by the comfort level they're gaining on the durability of Voxzogo in disproportionate skeletal dysplasias.

是的。謝謝杰夫，也謝謝阿卡什的詢問。就軟骨發育不全的持續時間而言，FDA 對 2 年的數據非常感興趣，而軟骨發育不全的持續時間則與 FDA 一致認為，為期 1 年的研究將得到支持——足以進行現場註冊。我認為這是由於他們在不成比例的骨骼發育不良中使用 Voxzogo 的耐用性所獲得的舒適度。

And as regards time lines for Noonan, really for further development beyond achondroplasia and hypochondroplasia, it does make sense that given that Voxzogo is an analog of a natural bone regulator -- bone growth regulator, it is anticipated that Voxzogo could be effective across a variety of indications, Noonans and others. This is being borne out in Dr. Dauber's IST evaluating a range of mutations, as you noted. He's treated at least 3 patients with Noonan syndrome for at least a year. And their growth velocity is maintained above their baseline, and importantly, good safety data are being collected in patients with Noonans.

至於 Noonan 的時間表，實際上是為了進一步發展軟骨發育不全和軟骨發育不良，考慮到 Voxzogo 是天然骨調節劑（骨生長調節劑）的類似物，預計 Voxzogo 可以在多種疾病中有效適應症，Noonans 等人。正如您所指出的，Dauber 博士評估一系列突變的 IST 證實了這一點。他已經治療了至少 3 名努南綜合徵患者至少一年。它們的生長速度保持在基線之上，重要的是，正在 Noonans 患者中收集良好的安全性數據。

We're in discussions with health authorities now to pin down anticipated eligibility, comparators, endpoints and study durations. And as we finalize those study designs, we'll communicate our plans more specifically as we have just done for hypochondroplasia. But your question really points out the exciting future potential of Voxzogo and other skeletal abnormalities based on its great safety record and its activity as a natural regulator of bone growth.

我們現在正在與衛生當局討論，以確定預期的資格、比較器、終點和研究持續時間。當我們最終確定這些研究設計時，我們將更具體地傳達我們的計劃，就像我們剛剛針對軟骨發育不全所做的那樣。但你的問題確實指出了 Voxzogo 和其他骨骼異常的令人興奮的未來潛力，基於其良好的安全記錄及其作為骨骼生長天然調節劑的活性。

Your next question comes from the line of Salveen Richter from Goldman Sachs.

您的下一個問題來自高盛的 Salveen Richter。

Can you help us to understand the confidence in Roctavian guidance for the second half in the context of the U.S. and EU dynamics?

您能否幫助我們理解在美國和歐盟動態的背景下對羅克塔維亞下半年指導的信心？

Maybe I'll start and I'll let -- I'll have Jeff going this. I think as Jeff said in the prepared remarks, based on the net price of Roctavian in the U.S., which is close to $2 million, the midpoint of our guidance economy of ours will be only 50 U.S. patients. We are counting in non-U.S. ex U.S. patients. And also just something that's special about Voxzogo because the gene therapy as compared to any forecast of chronic therapy is that starting a patient early in the year or late in the year makes the difference in terms of revenue recognition because Voxzogo, for instance, chronic therapy. If you start a patient on December 1, the revenues of this year will be much smaller than if you start them on [January 1]. But for Roctavian, if we treat a patient in -- on August 30, or on December 30, it's the same to the revenue. So just keep that in mind. With this introduction, Jeff?

也許我會開始，我會讓——我會讓傑夫來做這件事。我認為正如Jeff在準備好的發言中所說，根據Roctavian在美國接近200萬美元的淨價，我們指導經濟的中點將只有50名美國患者。我們正在計算非美國患者（前美國患者）。 Voxzogo 還有一點特別之處，因為與任何慢性療法的預測相比，基因療法在年初或年底開始治療患者會在收入確認方面產生差異，因為例如 Voxzogo，慢性療法。如果您在 12 月 1 日開始收治患者，那麼今年的收入將比在 [1 月 1 日]開始收治要少得多。但對於 Roctavian 來說，如果我們在 8 月 30 日或 12 月 30 日治療一名患者，收入是一樣的。所以請記住這一點。通過這個介紹，傑夫？

Yes. Thanks, JJ. I think that's exactly right. And thanks for the question, Salveen. The other couple of things that I would add are we're now seeing multiple pathways that we expect to open up for Roctavian revenue. I mentioned progress in all of Germany, Italy and France, which are priority European markets for price and reimbursement.

是的。謝謝，傑傑。我認為這是完全正確的。感謝薩爾文提出的問題。我要補充的另外幾件事是，我們現在看到了我們期望為 Roctavian 收入開闢的多種途徑。我提到了德國、意大利和法國的進展，這些國家是歐洲價格和報銷的優先市場。

Remember, I've been quoted on numerous occasions saying typically takes 12 to 15 months to get through that process. We're now just a couple of weeks away from 1 year since approval. So we should be getting to the end of the process in some or all of those markets between now and the end of the year, opening up a pathway for treating patients.

請記住，我曾多次被引用說通常需要 12 到 15 個月才能完成該過程。現在距離獲得批准僅剩幾週時間了。因此，從現在到今年年底，我們應該在部分或全部市場上完成這一過程，為治療患者開闢一條途徑。

Also the named patient markets I've quoted, Saudi Arabia and Argentina that we've been working diligently but quietly on in the background. And finally, the United States where we got our approval at the midyear point takes a couple of months for products availability and for start-up activities. But in the U.S., our experience has generally been that we can get patients treated pretty quickly after approval. So all of those things add up to channels for being able to treat patients and I think add to the confidence of being in that revenue guidance range.

還有我引用的指定患者市場，沙特阿拉伯和阿根廷，我們一直在後台默默地努力工作。最後，我們在年中獲得批准的美國需要幾個月的時間才能獲得產品和啟動活動。但在美國，我們的經驗通常是，在批准後我們可以很快地為患者提供治療。因此，所有這些因素加起來就成為能夠治療患者的渠道，我認為這增加了進入收入指導範圍的信心。

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

您的下一個問題來自美國銀行的 Geoff Meacham。

Just had a few. So for Roctavian in Europe, I know it's been a few months since you tweaked the access strategy in Germany. Are there any metrics you can give us, either activated centers or diagnostic volumes? I just want to get a sense for the progress since you've had a shift in the reimbursement strategy.

剛吃了幾個。因此，對於歐洲的 Roctavian，我知道自從您調整德國的訪問策略以來已經過去了幾個月。您可以向我們提供任何指標嗎？激活中心或診斷量？我只是想了解一下報銷策略發生轉變後的進展情況。

And then on Voxzogo, you talked, Hank, about Dr. Dauber's work expanding the indication base. I guess the question is, as you rolled out globally in achondroplasia commercially, have you identified hypochondroplasia patients? I wasn't sure if the new Phase III was sort of mechanism-driven or kind of commercially driven.

然後，漢克，您在 Voxzogo 上談到了 Dauber 博士擴大適應症基礎的工作。我想問題是，當您在全球範圍內推廣軟骨發育不全的商業化時，您是否已識別出軟骨發育不全患者？我不確定新的第三階段是機制驅動的還是商業驅動的。

Geoff, maybe I'll start with the question about Germany and Roctavian. As JJ quoted on our approval call, we've actually got a really robust funnel of patients now that are in process for eligibility testing, going through the CDx testing process, following eligible patients via CDx, go through liver health testing in minutes, a prescription and reimbursement approvals. So with -- as JJ quoted a month ago, approximately 60 patients, I view that as a really healthy patient funnel starting.

傑夫，也許我會從有關德國和羅克塔維安的問題開始。正如 JJ 在我們的批准電話會議上引用的那樣，我們實際上已經擁有了一個非常強大的患者漏斗，他們正在進行資格測試，通過 CDx 測試流程，通過 CDx 跟踪符合條件的患者，在幾分鐘內完成肝臟健康測試，處方和報銷批准。因此，正如 JJ 一個月前引用的那樣，大約有 60 名患者，我認為這是一個真正健康的患者漏斗的開始。

Recall last fall, we said we estimated about 40 early adopter patients in Germany. So we're at 1.5x that number, and that's before we get through the formal federal price and reimbursement process. Those patients are making progress inside of the funnel. And I understand it's frustrating not to see them popping out the other side as treated revenue patients, but I'm confident that they're making progress and that we'll get there, particularly if we can come to an agreement with the federal authorities on price and reimbursement.

回想一下去年秋天，我們估計德國有大約 40 名早期採用者患者。所以我們的價格是這個數字的 1.5 倍，而且這是在我們完成正式的聯邦價格和報銷流程之前。這些患者正在漏斗內取得進展。我知道，沒有看到他們作為接受治療的收入患者出現在另一邊是令人沮喪的，但我相信他們正在取得進展，我們會實現這一目標，特別是如果我們能夠與聯邦當局達成協議的話關於價格和報銷。

Maybe I'll turn that over to Hank on the Voxzogo question.

也許我會將 Voxzogo 問題轉交給漢克。

Thanks, Jeff. With a lot of the genetic conditions when there is no treatment, there tends to be no diagnosis. And now with achondroplasia gaining so much traction, patients with hypochondroplasia are identifying themselves or families with patients with hypochondroplasia are identifying themselves than getting themselves forwarded to treatment centers for identification, and in the case of Dr. Dauber's study, referral into his study. And I think a lot of that is driven by the phenotypic similarity of achondroplasia and hypochondroplasia, to your point about mechanistic similarity.

謝謝，傑夫。對於許多遺傳性疾病，如果不進行治療，往往無法診斷。現在，隨著軟骨發育不全獲得如此多的關注，軟骨發育不全患者正在識別自己，或者軟骨發育不全患者的家人也正在識別自己，而不是將自己轉送到治療中心進行識別，就道伯博士的研究而言，轉介到他的研究中。我認為這很大程度上是由軟骨發育不全和軟骨發育不全的表型相似性驅動的，正如您關於機制相似性的觀點一樣。

And our expectation is that this will begin to extend into other skeletal disorders as more clinicians and more families recognize CNP as a natural regulator of bone growth. And I think this is a process that could lead us to many additional indications. And as I said in the call, stay tuned for further updates on the regulatory strategy that will enable Roctavian to -- Voxzogo to be available for children suffering from other skeletal abnormalities beyond achondroplasia, hypochondroplasia. It's a very exciting time.

我們預計，隨著越來越多的臨床醫生和更多的家庭認識到 CNP 是骨骼生長的天然調節劑，這將開始擴展到其他骨骼疾病。我認為這個過程可能會給我們帶來許多額外的跡象。正如我在電話中所說，請繼續關注監管策略的進一步更新，該策略將使 Roctavian 能夠——Voxzogo 用於患有軟骨發育不全、軟骨發育不全以外的其他骨骼異常的兒童。這是一個非常激動人心的時刻。

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

您的下一個問題來自 Piper Sandler 的 Chris Raymond。

Just a couple of questions. First on the Voxzogo supply issue, Jeff, I wonder if you could maybe expand a little bit. I think I heard you say it's why the full year '23 guidance wasn't raised more. It's a supply issue at a CMO. But can you maybe expand on this? Like what exactly is fill-finish bottleneck? And I think you said you have supply to handle 2024 consensus, but just maybe could you put some brackets around the timing and the planned action to not be supply-constrained? Like what's the plan to sort of deal with the situation so it's no longer an issue?

只是幾個問題。首先是關於 Voxzogo 的供應問題，Jeff，我想知道你是否可以擴大一點。我想我聽到你說這就是為什麼 23 年全年指引沒有進一步提高的原因。這是 CMO 的供應問題。但你能擴展一下這個嗎？到底什麼是灌裝瓶頸？我想你說過你有供應來處理 2024 年的共識，但也許你可以在時間和計劃的行動中加上一些括號，以免受到供應限制？比如有什麼計劃來處理這種情況，使它不再是一個問題？

And then maybe for Hank on the pipeline. Just looking at the verbiage on 3/31, you've got 2 patients now where the expression trajectory is not yet into the therapeutic range. Maybe can you sort of talk about what would drive a go/no-go decision for this program? Or just any more color on there -- on that.

然後也許漢克也在籌備中。看看 3/31 的措辭，現在有 2 名患者的表達軌跡尚未進入治療範圍。也許您能談談是什麼推動了該計劃的進行/不進行決策？或者只是那裡有更多的顏色——就在那上面。

Thanks, Chris. We have Greg Guyer, our Head of Technical Operations here, who's going to answer your Voxzogo supply question.

謝謝，克里斯。我們的技術運營主管 Greg Guyer 將回答您的 Voxzogo 供應問題。

Yes, Chris, thanks for the question. And just maybe to clarify a little bit about what Jeff was talking about is that currently, we're able to supply Voxzogo with many hundreds of patients starts in the second half of this year and have a supply plan that exceeds even the 2024 consensus estimates that he mentioned earlier in FactSet. That said, that supply just remains tight from an inventory perspective. So we thought it was just appropriate just to escalate it to this group. My team is doing everything we can to continue to escalate or accelerate supply from the CMO which we use. They're a great partner, they're reliable, dependable, high compliance. So there's no issue. It's just trying to accelerate the supply availability faster than what we had planned. And that's really a tribute to our commercial team for really getting the type of penetration rates much faster than we had expected. And so we are working very closely with them to make sure that we can meet that future demand and also deliver on the full potential of Voxzogo long term.

是的，克里斯，謝謝你的提問。也許需要澄清一下 Jeff 所說的內容，目前，我們能夠在今年下半年開始向 Voxzogo 提供數百名患者，並且制定的供應計劃甚至超過了 2024 年的共識估計他之前在 FactSet 中提到過。也就是說，從庫存角度來看，供應仍然緊張。所以我們認為將其升級到這個群體是合適的。我的團隊正在盡一切努力繼續升級或加速我們使用的 CMO 的供應。他們是一個偉大的合作夥伴，他們是可靠的、可靠的、高度合規的。所以沒有問題。它只是試圖比我們計劃的更快地加快供應速度。這確實是對我們商業團隊的致敬，他們的滲透率比我們預期的要快得多。因此，我們正在與他們密切合作，以確保我們能夠滿足未來的需求，並充分發揮 Voxzogo 的長期潛力。

So again, there's no manufacturing issue. There is (inaudible) in terms of the manufacturing details in the drug substance, we manufacture ourselves here in California. The fill-finish is done by outside supplier. As you know, outside suppliers, there's a lot of lead time when you want to increase the volume. And that's what we're facing here because Voxzogo is doing way, way better than anybody, including ourself, anticipated in terms of penetration. That's what's creating a little -- it's a really limiting factor. But again, we believe it's going to ease up in '24. And then at the end of '24, in '25 and beyond, we shouldn't have any problem.

再說一次，不存在製造問題。在原料藥的製造細節方面（聽不清），我們在加利福尼亞州自己製造。填充完成由外部供應商完成。如您所知，對於外部供應商來說，當您想要增加產量時，需要很長的交貨時間。這就是我們在這裡面臨的問題，因為在滲透率方面，Voxzogo 的表現比任何人（包括我們自己）的預期都要好得多。這就是創造的一點——這是一個真正的限制因素。但我們再次相信，這種情況會在 24 年有所緩解。然後在 24 年底、25 年及以後，我們應該不會有任何問題。

But -- and we have -- Greg, almost unlimited drug substance capacity. I mean nothing is unlimited, but I would say we can clearly -- we have drug substance capacity to go way above $1 billion or probably $2 billion. And if we get more down the road, if need hypochon is successful, we can even go further. So it just feels -- it fill-finish bottleneck, which is temporary (inaudible) to have. But you're correct in your remark that actually, if we did have that bottleneck, we would have increased the guidance for ['23] higher, above what we are -- as we communicated today. But at the same time, the good news is that next year, we have -- we believe that our plan, including what our supplier can do in fill-finish front, will allow us to easily beat the current consensus for Voxzogo in 2024. And that should be much easier. Jeff, do you want to add anything?

但是 - 我們有 - 格雷格，幾乎無限的原料藥能力。我的意思是沒有什麼是無限的，但我想說我們可以清楚地——我們的原料藥產能遠遠超過 10 億美元或可能 20 億美元。如果我們能在這條路上取得更多進展，如果需求脅迫成功，我們甚至可以走得更遠。所以它只是感覺——它填補了瓶頸，這是暫時的（聽不清）。但你的評論是正確的，實際上，如果我們確實存在這個瓶頸，我們會將 ['23] 的指導提高到更高，高於我們今天所傳達的水平。但與此同時，好消息是，明年，我們相信我們的計劃，包括我們的供應商在填充完成方面可以做的事情，將使我們能夠輕鬆地在 2024 年擊敗目前 Voxzogo 的共識。這應該容易得多。傑夫，你想補充什麼嗎？

No, all stated. Thank you.

不，都說了。謝謝。

Is there any comment, Hank? Yes?

漢克，有什麼意見嗎？是的？

Yes. On 3/31, yes, Chris, we do have very clear criteria for staffing, and note would be taken that at this stage. One option could be before reaching those top criteria to raise the dose. AAV5-based therapies have a pretty good safety profile. And so we could contemplate raising the dose. Another thing I'll mention is that new -- and I'm not going to be very specific about this just yet, but we -- with as much Roctavian data as we have, we have some new insights about optimizing gene expression in patients treated with gene therapy. And we're working very closely with the Data Monitoring Committee and the investigators of the study to incorporate those insights. And if neither of those 2 are successful, of course, we would meet a stop criteria. But it's still a little bit early for that program. And as we resume dosing and obtain more data, we'll provide further updates.

是的。 3 月 31 日，是的，克里斯，我們確實有非常明確的人員配置標準，並且在現階段需要注意這一點。一種選擇可能是在達到這些最高標準之前提高劑量。基於 AAV5 的療法具有相當好的安全性。因此我們可以考慮提高劑量。我要提到的另一件事是新的——我現在還不會具體說明這一點，但是我們——有了盡可能多的 Roctavian 數據，我們對優化患者基因表達有了一些新的見解通過基因療法進行治療。我們正在與數據監測委員會和研究人員密切合作，以整合這些見解。當然，如果這兩個都不成功，我們就會滿足停止標準。但該計劃還為時過早。當我們恢復給藥並獲得更多數據時，我們將提供進一步的更新。

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

您的下一個問題來自 Truist Securities 的 Robyn Karnauskas。

I'll be quick. So 3 questions. Number one, we heard compliance is very high in Voxzogo. Can you elaborate? And that gets to the competitive landscape and how committed interns are. Number two, there's questions around hypochondroplasia. Like do you have to do as many studies -- long-term studies? Any insight into that? And then I have one follow-up.

我會快點的。所以 3 個問題。第一，我們聽說 Voxzogo 的合規性非常高。你能詳細說明一下嗎？這涉及到競爭格局以及實習生的忠誠度。第二，關於軟骨發育不全的問題。就像你必須做同樣多的研究——長期研究嗎？有什麼見解嗎？然後我有一個後續行動。

Maybe start with a question on compliance with Voxzogo, Robyn. And as you note, it's very high. We are not able to measure that explicitly in all markets. So the one market that we can really dial in on that is the United States. And our experience so far in the United States is very few drop-offs and compliance with the daily dosing as we measure it appears to be very high. So, so far, so good on the compliance side. And maybe I'll turn it over to Hank.

也許可以從關於遵守 Voxzogo 的問題開始，Robyn。正如您所注意到的，它非常高。我們無法在所有市場中明確衡量這一點。因此，我們真正可以涉足的市場就是美國。到目前為止，我們在美國的經驗很少有下降，而且我們測量的每日劑量依從性似乎非常高。因此，到目前為止，合規性方面表現良好。也許我會把它交給漢克。

Yes, thanks, Jeff. In regard to the hypochondroplasia question, one study we've interacted with the Food and Drug Administration and have a pretty clear picture of their requirements which would be satisfied with one study. And the reason for not requiring longer-term follow-up as regards randomized placebo-controlled period is their growing satisfaction with durability. In fact, maybe to go even a little further, depending on where achondroplasia is at the time of the regulatory action on hypochondroplasia, even further follow-up may no longer be required for hypochondroplasia. So we had a great dialogue with the FDA. And in so far as there's an excellent safety track record for Voxzogo in patients with hypochondroplasia with accumulating excellent efficacy data, these sorts of supplemental new drug applications are not subject to necessarily the same demand as the initial dose. So pretty excited. And you mentioned you had a follow-up question?

是的，謝謝，傑夫。關於軟骨發育不全的問題，我們與美國食品和藥物管理局進行了一項研究，對他們的要求有一個非常清晰的了解，一項研究就可以滿足這些要求。不需要對隨機安慰劑對照期進行長期隨訪的原因是他們對持久性越來越滿意。事實上，也許更進一步，根據對軟骨發育不全採取監管行動時軟骨發育不全所處的位置，軟骨發育不全可能不再需要進一步的隨訪。因此我們與 FDA 進行了一次很好的對話。到目前為止，Voxzogo 在軟骨發育不全患者中擁有出色的安全記錄，並積累了出色的療效數據，此類補充新藥申請不一定需要與初始劑量相同的需求。非常興奮。你提到你有一個後續問題？

Yes. One follow-up, sorry. So there's so much fixation on when you'll dose patients in Europe. And I was just curious, like have you thought about like letting us know earlier or during the Analyst Day. There's some expectation on that. So maybe give us clarity on when you might give us timing of that and how much color you would give because there's excitement, but we're yet to see the dosing.

是的。後續一話，抱歉。因此，在歐洲，對於何時給患者服用藥物有很多規定。我只是很好奇，你有沒有想過提前或在分析師日期間讓我們知道。對此有一些期待。因此，也許可以讓我們清楚地知道您何時可以給我們時間以及您會提供多少顏色，因為這很令人興奮，但我們還沒有看到劑量。

Yes. Actually, one -- Robyn, one of your financial analyst competitor had a recent call with a German physician. That German physician announced on that call, but starts revision on that, that is scheduled to treat his first patient, I think, on August 30 or August 31. So that looks like this one is probably a given. And then there is the possibility that we would treat also our first rest patients by the end of August, (inaudible). And then after last September should be when we're going to start really getting some real traction on patient treatments and revenues.

是的。事實上，羅賓，你的一位金融分析師競爭對手，最近與一位德國醫生通了電話。那位德國醫生在那次電話會議上宣布了這一消息，但開始對此進行修改，我認為計劃在 8 月 30 日或 8 月 31 日治療他的第一位患者。所以看起來這可能是既定的。然後我們有可能在八月底之前治療第一批休息的患者（聽不清）。去年九月之後，我們應該開始真正在患者治療和收入方面獲得一些真正的推動力。

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

您的下一個問題來自 Cowen 的 Phil Nadeau。

A couple more on Roctavian. JJ, during your prepared remarks you mentioned the consent form received in the U.S. as adding confidence to the guidance. Can you go into a bit more detail on that comment? Is that simply the 300 patients that you knew of as of the time of approval? Or have there been incremental consent forms received over the last month?

還有一些關於羅克塔維安的。 JJ，在您準備好的發言中，您提到在美國收到的同意書增加了對指南的信心。您能更詳細地介紹一下該評論嗎？這只是您在批准時所知道的 300 名患者嗎？或者上個月是否收到了增量同意書？

I'll let Jeff answer that question. I don't want to believe that. We already received 300 patients consent form. We haven't, but they're starting to roll in and -- but maybe Jeff can provide some more color here.

我會讓傑夫回答這個問題。我不想相信這一點。我們已經收到 300 名患者的同意書。我們還沒有，但他們開始加入進來——但也許傑夫可以在這裡提供更多的色彩。

Yes. Thanks for the question, Phil. So these are really independent sets of patients. The 300 patients that we've quoted are qualified leads means we have a lead. We've qualified that lead to be a hemophilia patient, not a sales rep at a competitor company, for example. And we're following up those patients have opted in for further information.

是的。謝謝你的提問，菲爾。所以這些是真正獨立的患者組。我們引用的 300 名患者都是合格的潛在客戶，這意味著我們擁有領先優勢。例如，我們已將其認定為血友病患者，而不是競爭對手公司的銷售代表。我們正在追踪那些選擇獲取更多信息的患者。

Patient consent forms, on the other hand, are usual vehicle that we use for all of our programs, including for Roctavian in the United States, to conduct patient intake into our case management system. So any patient that's come in with a patient consent form has been in touch with our case management system and has opted in for further services, depending -- that patient consent form might be coming in from a hemophilia treatment center along with prescription or might be coming in independently as patient-directed interest. And in that case, we would connect them with the sales rep for follow-up. So it's a mix, but it's really, really good that we have patient consent forms coming into our case management system. That's how it always begins for us with all of our programs, including Roctavian.

另一方面，患者同意書是我們所有項目（包括美國的 Roctavian）常用的工具，用於將患者納入我們的病例管理系統。因此，任何持有患者同意書的患者都已與我們的病例管理系統聯繫，並選擇接受進一步的服務，具體取決於患者同意書可能來自血友病治療中心以及處方，或者可能來自血友病治療中心。作為以患者為導向的興趣獨立出現。在這種情況下，我們會將他們與銷售代表聯繫起來進行跟進。所以這是一個混合體，但將患者同意書納入我們的病例管理系統真的非常非常好。這就是我們所有項目（包括 Roctavian）的開始方式。

Would you care to disclose how many patient consent forms you have?

您願意透露您有多少份患者同意書嗎？

Not at this time. Thanks for the effort, though.

目前還不行。不過還是謝謝你的努力。

Got it. And then in terms of the centers themselves, what do they need to do in order to make Roctavian available for a patient? In general, do they -- does there -- is there a formulary committee that has to accept Roctavian as a therapy? Any other committees that you have to talk to or get permission from before a center can bring Roctavian to its patients?

知道了。那麼就中心本身而言，他們需要做什麼才能為患者提供 Roctavian 服務？總的來說，他們是否——有——是否有一個處方委員會必須接受羅克塔維安作為一種療法？在中心將 Roctavian 帶給患者之前，您必須與任何其他委員會交談或獲得許可？

It's a great and an important question, the notion of site readiness. And unfortunately, there's no kind of simple one-size-fits-all description. Some HTCs are connected to a larger health care system. In those cases, an HTC might tap into the administrative procedures that you mentioned, like formulary, for example, and maybe also pharmacy services from the larger institution. And in other cases, you have hemophilia treatment centers that are more or less standalone and do all of that on their own. So site readiness looks different depending on what is the size capability of the HTC and are they connected or not with a larger health care institution.

這是一個偉大而重要的問題，即站點準備情況的概念。不幸的是，沒有一種簡單的一刀切的描述。一些 HTC 與更大的醫療保健系統相連。在這些情況下，HTC 可能會利用您提到的行政程序，例如處方集，也可能利用大型機構的藥房服務。在其他情況下，血友病治療中心或多或少是獨立的，並且自己完成所有這些工作。因此，現場準備情況看起來會有所不同，具體取決於 HTC 的規模能力以及它們是否與較大的醫療保健機構有聯繫。

Just a reminder, the infusion of Roctavian is a relatively trivial step. But the more important things are issues like the administration, formulary, for example, navigating payer interactions, product handling of a very frozen product that has a high value, for example, patient eligibility testing and counseling to determine if there's a patient with interest and if so, moving them forward in the process and then the follow-up following administration, which we talked about on the approval call. So lots going on there. None of those things involve a big hurdle. It's mostly a bunch of smaller things that need to be done and a whole list of them for -- that is rather bespoke for each hemophilia treatment center, and our team is on it.

提醒一下，注入 Roctavian 是一個相對簡單的步驟。但更重要的事情是管理、處方集等問題，例如，導航付款人互動、具有高價值的高度冷凍產品的產品處理，例如，患者資格測試和諮詢，以確定是否有患者感興趣和如果是這樣，請在這一過程中推動他們前進，然後推進後續管理，我們在批准電話會議上談到了這一點。那裡發生了很多事情。這些事情都不涉及大障礙。這主要是一堆需要完成的小事情以及一整套清單——這是為每個血友病治療中心量身定制的，我們的團隊正在參與其中。

Great. And then last one is on that follow-up that you just mentioned. How onerous are the liver enzyme and factor monitoring requirements? Is that something that you can make very easy for the patients?

偉大的。最後一個是關於您剛才提到的後續行動。肝酶和因子監測要求有多繁重？您可以讓患者變得非常容易嗎？

Blood test. Liver function tests are on a panel that probably most of us do once or twice a year. It's a simple blood test. At the same time that, that simple blood test is being taken. That blood can be used for factor expression levels.

驗血。肝功能測試是在一個面板上進行的，我們大多數人可能每年都會進行一次或兩次。這是一個簡單的血液檢查。與此同時，正在進行簡單的血液檢查。該血液可用於測定因子表達水平。

Hope the patients do that? Do you want to...

希望患者這樣做嗎？你想要_____嗎...

That's right. So for a lot of patients, it's as simple as going to a very nearby lab testing facility. In the case of patients that don't have convenient access to that, we have programs to assist.

這是正確的。因此，對於很多患者來說，這就像前往附近的實驗室檢測設施一樣簡單。如果患者無法方便地獲得這些服務，我們有一些計劃可以提供幫助。

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

您的下一個問題來自 Leerink Partners 的 Joseph Schwartz。

Our checks in Germany indicate that there is still some uncertainty about how many and which sites will be able to administer Roctavian there. So I was wondering if you could talk about how this rule-making process works and how you expect it to play out. Is this part of the reimbursement negotiations, which you're expected to wrap up in September? Or is this something separate?

我們在德國的檢查表明，有多少個站點以及哪些站點能夠在那裡管理 Roctavian 仍然存在一些不確定性。所以我想知道你是否可以談談這個規則制定過程是如何運作的以及你期望它如何進行。這是您預計將於 9 月結束的報銷談判的一部分嗎？或者這是單獨的東西？

And then in the U.S., our checks underscore the importance of contracting with the sites that the initial ordering and longer-term follow-up on patient performance can be done reliably. So I was wondering sort of a follow-on to Phil's question, if you can give us any insight into the extent of contracting that you've been doing with HTCs in the U.S.

然後在美國，我們的檢查強調了與可以可靠地完成初始訂購和對患者表現的長期隨訪的網站簽訂合同的重要性。因此，我想知道 Phil 問題的後續內容，您能否向我們介紹一下您在美國與 HTC 簽訂合同的程度？

Joe, let me start with Germany. So you've heard me talk over the last year or even longer about the hub-and-spoke model for treatment that the major markets in Europe have been rallying around. And that's the hemophilia treatment community in Europe, not BioMarin is a driver behind that. So the notion is that, in Germany, for example, the largest and the most capable hemophilia treatment centers would be hub centers for both screening and testing patients and that there would be smaller, less capable hemophilia treatment centers that would be spoke centers. And those spoke centers would probably do all of the screening and recommending of treatment. The treatment would be done at the hub center and then likely back to the spoke center for a follow-up after treatment.

喬，讓我從德國開始。所以你在過去一年甚至更長的時間裡都聽到我談論歐洲主要市場一直在支持的中心輻射型治療模式。這就是歐洲的血友病治療界，而不是 BioMarin 是其背後的推動者。因此，我們的想法是，以德國為例，最大、最有能力的血友病治療中心將成為篩查和測試患者的中心中心，而規模較小、能力較差的血友病治療中心將成為輻射中心。這些發言人中心可能會進行所有的篩查和治療建議。治療將在輪轂中心進行，然後可能返回輪輻中心進行治療後的後續治療。

There may, in fact, be a little bit of uncertainty on the entire list of who's the hub and who's the spoke. But from a practical perspective, we're focused on engaging with all of the significant hemophilia treatment centers in Germany. And it doesn't really matter very much from a kind of promotional perspective, which centers do infusions and which centers refer for infusions on Germany.

事實上，誰是中心、誰是輻條的整個列表可能存在一些不確定性。但從實際角度來看，我們專注於與德國所有重要的血友病治療中心合作。從促銷的角度來看，哪些中心做輸液以及哪些中心推薦德國輸液並不重要。

You mentioned contracting, and I'm not sure exactly what kind of contracting you're talking about. In the United States, there would certainly need to be an agreement reached between a treatment center and a payer on the level of reimbursement for Roctavian, which might involve a patient-specific contract between a hemophilia treatment center and a payer. We think that that's likely and not a big barrier at all to proceed with the treatment.

你提到了承包，我不確定你所說的承包是哪種類型。在美國，治療中心和付款人之間肯定需要就 Roctavian 的報銷水平達成協議，這可能涉及血友病治療中心和付款人之間針對特定患者的合同。我們認為這很可能，而且根本不是繼續治療的大障礙。

There might also be contracting between spoke sites, to use the analogy, spoke sites and hub sites in the United States, if there's a desire on the part of a hemophilia treatment center to refer one of their patients to a more capable center or one that's further along in site readiness for treatment of Roctavian. All of those things are possible. I haven't personally heard that there are any barriers to proceeding due to contracting. If you've got something more specific, [we'll start].

打個比方，如果血友病治療中心希望將一名患者轉診至能力更強的中心或能力更強的中心，那麼分支站點之間也可能會簽訂合同，即美國的分支站點和中心站點。進一步推進羅克塔維安治療的現場準備工作。所有這些都是可能的。我個人還沒有聽說過因簽訂合同而造成任何進展障礙。如果您有更具體的信息，[我們將開始]。

No, that's good.

不，那很好。

Sorry, I may add, Joe, as gave some of our investor aisles. Basically, all patients in the U.S. will be treated with Roctavian in hemophilia treatment centers are chemo treatment centers that are receiving 340B discounts, basically statutory for the centers. Let's take around -- it will be initially more than 20%, and it might go down to 17.5%, whatever. But let's round it to 20%. That's 20% of the WACC cost. So a WACC is $3 million a patient. So 20% is $600,000 that will go in the pocket of the HTCs per patient. So you might have this information -- or you might find this information interesting.

抱歉，喬，我可以補充一下，就像我們的一些投資者通道一樣。基本上，美國的所有患者都會在血友病治療中心接受 Roctavian 治療，這些治療中心都是化療中心，享受 340B 的折扣，這基本上是這些中心法定的折扣。讓我們考慮一下——最初會超過 20%，然後可能會下降到 17.5%，無論如何。但我們將其四捨五入為 20%。這是 WACC 成本的 20%。因此，WACC 相當於每位患者 300 萬美元。因此，20% 也就是 600,000 美元將落入每位患者 HTC 的口袋。因此，您可能擁有此信息，或者您可能會發現此信息很有趣。

Very much so.

非常如此。

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

您的下一個問題來自 Stifel 的 Paul Matteis。

On Voxzogo, Jeff, does the supply issue or, I guess, capacity issue temporarily impact how you market the drug? And how might that impact the way you sort of seek to interact with health care providers and patients if and when the label is expanded before the capacity constraint is fully resolved.

關於 Voxzogo，Jeff，供應問題或者我猜產能問題是否會暫時影響您銷售藥物的方式？如果在容量限製完全解決之前擴大標籤，這可能會如何影響您尋求與醫療保健提供者和患者互動的方式。

And then on Roctavian just in terms of the timing, the 2- to 5-month timing that you spoke to around approval, I think it took around 7 months to dose the first Hemgenix patient. Can you just outline the couple of key reasons in your mind for why you think you can get this done so much faster than CSL did?

然後就 Roctavian 而言，就時間而言，您談到批准的 2 到 5 個月時間，我認為為第一位 Hemgenix 患者給藥大約需要 7 個月。您能否概述一下您認為自己能比中超更快地完成這項工作的幾個關鍵原因？

Yes, good question. I'll start on the Voxzogo and then Jeff can chip in. Again, when -- in our prepared remarks and our -- we said that for 2024, we will have ample supply to beat the current consensus, which is close to $600 million. So for us, that includes a potential increase of -- I mean label expansion in terms of new patients. New patients are under AAV5, if that does occur, some. So that's already included. So it doesn't share anything in the remarks that we made in this respect. I mean, Greg, do you have anything to add here?

是的，好問題。我將從 Voxzogo 開始，然後 Jeff 可以插話。同樣，在我們準備好的發言和我們的發言中，我們說過，到 2024 年，我們將有充足的供應來打破目前的共識，即接近 6 億美元。因此，對我們來說，這包括潛在的增加——我的意思是新患者的標籤擴展。新患者處於 AAV5 之下，如果確實發生的話，會有一些。所以這已經包括在內了。因此，它與我們在這方面所做的言論沒有任何共同之處。我的意思是，格雷格，你還有什麼要補充的嗎？

No. And by the time hypochon comes, this supply issue will not be one -- we'll have plenty of supply.

不會。到季風到來時，供應問題將不再是問題——我們將擁有充足的供應。

Yes, we're not going to get hypochon -- the hypochon indication is next year.

是的，我們不會患上憂鬱症——憂鬱症的跡像是明年。

I just meant younger patients, but okay.

我只是指年輕的患者，但是沒關係。

Younger patients, but that's already, I guess, the current consensus is significantly above the top of our guidance for this year of $440 million. And we are very comfortable with -- we have enough supply to significantly beat the current 2024 consensus, whatever the patients are. But Jeff, do you want to add anything to...

年輕的患者，但我想，目前的共識已經大大高於我們今年 4.4 億美元的指導上限。我們非常滿意——無論患者是什麼，我們都有足夠的供應來顯著超過目前的 2024 年共識。但是傑夫，你想添加什麼嗎...

Yes. Maybe just a couple of metrics to put it into perspective. At the end of Q1, we advised that there were 1,500 patients on treatment around the world; the end of Q2, 2,000 patients on treatment around the world. That's a big increase quarter-to-quarter. And we've guided that our supply plan just through the end of this year allows for hundreds of additional patients to gain therapy. So internally, how we're looking at this is -- the overall demand is not a big surprise. It's just coming sooner and the uptake is coming faster in markets that we're gaining access to. So gaining access sooner, faster uptake in those markets than we were planning on. We still need and want that patient base to grow. And so it doesn't fundamentally alter our launch of this drug. This is a really good growth trajectory for us. We're just bumping into some ceilings in certain places.

是的。也許只需幾個指標就可以正確地看待它。截至第一季度末，我們告知全球有 1,500 名患者正在接受治療；截至第二季度末，全球有 2,000 名患者正在接受治療。這是一個季度比一個季度的大幅增長。我們指導我們的供應計劃到今年年底為止，可以讓數百名額外的患者獲得治療。因此，在內部，我們的看法是——總體需求並不令人意外。它只是來得更快，而且在我們進入的市場中吸收速度更快。因此，比我們計劃的更早、更快地進入這些市場。我們仍然需要並希望擴大患者群體。因此，它並沒有從根本上改變我們推出這種藥物的情況。這對我們來說是一個非常好的增長軌跡。我們只是在某些地方遇到了天花板。

And where that's happening, we're prioritizing, keeping kids that have started or will start, make sure that we've got continuity of supply because what we really don't want to have happen is for kids that have started supply to go off therapy. That much on Voxzogo.

在發生這種情況的情況下，我們會優先考慮，保留已經開始或將要開始的孩子，確保我們的供應連續性，因為我們真正不希望發生的情況是已經開始供應的孩子停止供應治療。關於 Voxzogo 就這麼多了。

On Roctavian -- for Roctavian, we're highly motivated to treat patients in the United States as rapidly as possible. On the one hand, we are a new entrant to hemophilia. We've been preparing for this day for a number of years. But it's not like we have an existing therapy that we need to cannibalize with the treatment of our gene therapy. And we've taken steps, for example, having a group purchasing organization contract signed before we even got approval. We took those steps to facilitate rapid access. We're moving as quickly as possible. We've got the warranty. So those are differentiating factors. I can't speak for the other manufacturer. But we're moving as rapidly as possible. And I think the steps that we've taken so far would be consistent with that desire to move fast.

關於 Roctavian——對於 Roctavian 來說，我們非常積極地盡快治療美國的患者。一方面，我們是血友病的新進入者。為了這一天，我們已經準備了很多年。但這並不是說我們有一種現有的療法，需要我們的基因療法來替代。我們已經採取了一些措施，例如，在獲得批准之前就簽署了集團採購組織合同。我們採取這些步驟是為了促進快速訪問。我們正在盡快行動。我們有保修。所以這些都是差異化因素。我不能代表其他製造商說話。但我們正在盡快行動。我認為我們迄今為止所採取的步驟將符合快速行動的願望。

And several payers have already signed a warranty contract. That means that I presume they are intending to cover Voxzogo. Otherwise, there will be no need for them to do that.

並且多家付款人已經簽訂了保修合同。這意味著我認為他們打算報導 Voxzogo。不然的話，他們也沒有必要這麼做。

Your next question comes from the line of Gena Wang from Barclays.

您的下一個問題來自巴克萊銀行的 Gena Wang。

Maybe just follow Paul's comment -- question and also JJ, your comments. Maybe for Roctavian 2023 revenue, first, do you expect most revenue from Germany or U.S.? And regarding U.S. payers, what is the feedback on one warranty program since you just mentioned? And how many centers and lives under the coverage right now are in place?

也許只是關注 Paul 的評論——問題以及 JJ，你的評論。也許對於 Roctavian 2023 年的收入，首先，您預計大部分收入來自德國還是美國？至於美國付款人，您剛才提到的一項保修計劃的反饋是什麼？目前有多少個中心和生命受到覆蓋？

Second question is regarding the Voxzogo in hypochondroplasia. So regarding the 6-month observation study, what would you be looking for to help define the pivotal study? And for a 52-week pivotal study, what is the trial assumption? And how much you actually learned from Dr. Andrew Dauber's trial?

第二個問題是關於 Voxzogo 在軟骨發育不全中的應用。那麼對於為期 6 個月的觀察研究，您會尋找什麼來幫助定義關鍵研究？對於為期 52 週的關鍵研究，試驗假設是什麼？您實際上從安德魯·道伯博士的試驗中學到了多少？

Maybe I'll start, Gena, and I'll let JJ fill in. In terms of revenue expectations for Roctavian and where, as I noted, in Salveen's question, part of the confidence in our guidance is not only the U.S. approval that we received when we did the price that we've named for the United States, but the fact that now almost 12 months from the conditional approval in Europe, we're approaching that period of time where you would expect we would be able to finish getting through formal price and reimbursement processes, at least in the initial major markets in Europe.

也許我會開始，Gena，我會讓 JJ 來補充。就 Roctavian 的收入預期而言，正如我在 Salveen 的問題中指出的那樣，對我們指導的部分信心不僅在於美國對我們的認可當我們為美國製定價格時收到的價格，但事實是，距離歐洲有條件批准已近 12 個月，我們正在接近您期望我們能夠完成獲得的時間通過正式的價格和報銷流程，至少在歐洲最初的主要市場是這樣。

That together with what I've described on a couple of occasions to questions is what we think is a rapid start in the United States. And even the possibility of named patient sales in other markets, those channels give different, different opportunities for patients to get treated and contribute to revenue.

連同我在幾次提問中所描述的內容，我們認為美國正在迅速起步。即使在其他市場進行指定患者銷售的可能性，這些渠道也為患者提供了不同的接受治療和貢獻收入的機會。

In terms of percent coverage and lives, actually, we don't have coverage policies issued in the United States yet, at least that I'm aware of. Those policies can take anywhere from 1 to 12 months to issue. I've seen some draft language around coverage policies that have not yet been issued that would indicate that those coverage policies will be consistent with either a label or a clinical trial inclusion criteria, which -- both of which would be fine. We haven't seen those coverage policies start to be issued yet. So I can't comment on what percent of covered lives in the United States.

實際上，就覆蓋率和生命而言，我們在美國還沒有發布保險單，至少據我所知。這些政策可能需要 1 到 12 個月的時間才能發布。我看到了一些尚未發布的關於承保政策的草案語言，這些草案表明這些承保政策將與標籤或臨床試驗納入標準一致，這兩者都很好。我們還沒有看到這些保險政策開始發布。所以我無法評論美國受保人數的百分比。

And maybe I would turn it over to Hank for the questions on Voxzogo and hyperchon.

也許我會把它交給 Hank，詢問有關 Voxzogo 和 hyperchon 的問題。

Yes, Gena, the 6-month prospective run-in study is important to document baseline annualized growth rate prior to randomization into the study. As we talked about before, one of the things that we observed in the growth disorder area is that, that knowledge of that baseline growth rate is really important to be able to interpret subsequent changes in growth velocity and is important for randomization purposes. The study, as I mentioned, is in 80 participants, which is a little bit smaller than the study of Voxzogo in achondroplasia, where we are expecting a relatively similar magnitude of effect. Of course, that can be tuned depending on what that baseline AGV run in is for the baseline population.

是的，Gena，為期 6 個月的前瞻性磨合研究對於記錄隨機進入研究之前的基線年化增長率非常重要。正如我們之前談到的，我們在生長障礙領域觀察到的一件事是，了解基線增長率對於能夠解釋生長速度的後續變化非常重要，並且對於隨機化目的也很重要。正如我提到的，這項研究有 80 名參與者，比 Voxzogo 治療軟骨發育不全的研究規模要小一些，我們預計該研究的效果程度相對相似。當然，這可以根據基線 AGV 運行的基線人口進行調整。

But just to remind you, in the 110-patient study of Voxzogo in achondroplasia, the P value is 10 to minus 13. So we don't anticipate needing to power the study quite as aggressively as we did in achondroplasia. And we're reassured about all of this based on the evolving data that we've seen from Dr. Dauber as has the FDA been reassured that we can go directly into a Phase III clinical trial. So thanks for the questions.

但提醒您一下，在 Voxzogo 治療軟骨發育不全的 110 名患者的研究中，P 值為 10 至負 13。因此，我們預計不需要像在軟骨發育不全中那樣積極地推動這項研究。基於我們從 Dauber 博士那裡看到的不斷變化的數據，我們對這一切感到放心，FDA 也保證我們可以直接進入 III 期臨床試驗。謝謝你的提問。

That concludes the Q&A portion of our conference call. We will turn it back to BioMarin's CEO, JJ Bienaime, for closing remarks.

我們電話會議的問答部分到此結束。我們將把它轉回 BioMarin 的首席執行官 JJ Bienaime 進行結束語。

Thank you, operator, and thank you all for joining us on the call today. Outstanding execution across our business led to record revenues in the first half of 2023. We reached more children with Voxzogo around the world as physicians and family start treatment with the only approved medicine starting in the generic use of achondroplasia. And we are well on our way to begin treating patients in the U.S. and Europe with Roctavian over the coming months. So for the remainder of 2023, we plan to build on the foundation of growth and profitability achieved in the first half of the year. Thank you for your support, and have a good day.

謝謝接線員，也感謝大家今天加入我們的電話會議。我們整個業務的出色執行力使我們在 2023 年上半年實現了創紀錄的收入。隨著醫生和家庭開始使用唯一經批准的軟骨發育不全仿製藥藥物進行治療，我們在世界各地為更多兒童提供了 Voxzogo。我們正在順利地在未來幾個月內開始使用 Roctavian 治療美國和歐洲的患者。因此，在 2023 年剩餘時間裡，我們計劃在上半年實現的增長和盈利能力的基礎上再接再厲。感謝您的支持，祝您有美好的一天。

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。