Ascendis Pharma A/S (ASND) 2024 Q4 法說會逐字稿

Good day and thank you for standing by. Welcome to the fourth-quarter and full year 2024 Ascendis Pharma earnings conference call. (Operator Instructions) Please be advised that today's conference is being recorded.

您好，感謝您的支持。歡迎參加 Ascendis Pharma 2024 年第四季和全年財報電話會議。（操作員指示）請注意，今天的會議正在錄音。

I would now like to hand the conference over to Scott Smith, Chief Financial Officer. Please go ahead.

現在我想將會議交給財務長 Scott Smith。請繼續。

Thank you very much, operator, and thank you, everyone, for joining our full year 2024 financial results conference call. I'm Scott Smith, Chief Financial Officer at Ascendis Pharma. Joining me on the call today are Jan Mikkelsen, President and Chief Executive Officer; Sherrie Glass, Chief Business Officer; Jay Wu, President, US Market; and Aimee Shu, Chief Medical Officer.

非常感謝接線員，也感謝大家參加我們的 2024 年全年財務業績電話會議。我是 Ascendis Pharma 的財務長 Scott Smith。今天與我一起參加電話會議的還有總裁兼執行長 Jan Mikkelsen； Sherrie Glass，首席商務長； Jay Wu，美國市場總裁；以及首席醫療官 Aimee Shu。

Before we begin, I would like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the safe harbor provided by the Private Securities Litigation Reform Act.

在我們開始之前，我想提醒您，本次電話會議將包含前瞻性陳述，這些陳述旨在受到《私人證券訴訟改革法案》提供的安全港的保護。

Examples of such statements may include, but are not limited to, statements regarding our commercialization and continued development of SKYTROFA and YORVIPATH for the US, European, and other markets as well as certain financial expectations; our pipeline candidates and our expectations with respect to their continued progress and potential commercialization; our strategic plans, partnerships and investments; our goals regarding our clinical pipeline, including the timing of clinical trials and results; our ongoing and planned regulatory filings and our expectations regarding the timing and the results of regulatory decisions; expected market developments and our exploration of market opportunities in therapeutic areas outside of endocrinology rare disease.

此類聲明的範例可能包括但不限於有關我們對美國、歐洲和其他市場進行 SKYTROFA 和 YORVIPATH商業化和持續開發的聲明以及某些財務預期；我們的候選產品以及我們對其持續進展和潛在商業化的期望；我們的策略計劃、合作夥伴關係和投資；我們關於臨床管線的目標，包括臨床試驗的時間和結果；我們正在進行和計劃中的監管備案以及我們對監管決定的時間和結果的預期；預期的市場發展以及我們正在進行和計劃中的監管備案以及我們對監管決定的時間和結果的預期；預期的市場發展以及我們對內分泌疾病以外的市場發展。

These statements are based on information that is available to us today. Actual results may differ materially -- could differ materially from those in our forward-looking statements, and you should not place undue reliance on these statements. We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning the factors that could cause actual results to differ materially, please see our forward-looking statements section in today's press release and the Risk Factors section of our most recent annual report on Form 20-F filed with the SEC today, February 12, 2025.

這些聲明是基於我們今天所掌握的資訊。實際結果可能存在重大差異—可能與我們的前瞻性陳述有重大差異，您不應過度依賴這些陳述。除非法律要求，我們不承擔隨著情況變化而更新這些聲明的義務。有關可能導致實際結果出現重大差異的因素的更多信息，請參閱今天新聞稿中的前瞻性陳述部分以及我們於 2025 年 2 月 12 日向美國證券交易委員會提交的最新 20-F 表年度報告中的風險因素部分。

TransCon Growth Hormone or TransCon hGH is approved in the US by FDA and in the EU has received MAA authorization from the European Commission for the treatment of pediatric growth hormone deficiency. TransCon PTH is approved in the US by the FDA for the treatment of hypoparathyroidism in adults. And the European Commission and the United Kingdom's Medicines and Healthcare products Regulatory Agency have granted marketing authorization for TransCon PTH as a replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism.

TransCon 生長激素或 TransCon hGH 在美國已獲得 FDA 批准，在歐盟已獲得歐盟委員會的 MAA 授權，用於治療兒童生長激素缺乏症。TransCon PTH 已獲得美國 FDA 批准用於治療成人副甲狀腺功能減退症。歐盟委員會和英國藥品和保健產品管理局已授權 TransCon PTH 作為治療成人慢性副甲狀腺功能減退症的替代療法。

Otherwise, please note that our product candidates are investigational and not approved for commercial use. As investigational products, the safety and effectiveness of product candidates have not been reviewed or approved by any regulatory agency. None of the statements during this conference call regarding our product candidates shall be viewed as promotional.

否則，請注意，我們的候選產品尚處於研究階段，尚未獲準用於商業用途。作為研究產品，候選產品的安全性和有效性尚未經過任何監管機構的審查或批准。本次電話會議中有關我們候選產品的任何聲明均不應被視為促銷。

On the call today, we will discuss our full year 2024 financial results, and we'll provide further business updates. Following some prepared remarks, we will then open up the call for questions.

在今天的電話會議上，我們將討論 2024 年全年財務業績，並提供進一步的業務更新。在發表一些準備好的發言之後，我們將開始提問。

With that, let me turn it over to Jan.

現在，讓我把時間交給 Jan。

Thanks, Scott, and good afternoon, everyone. 2024 was a favorable year for Ascendis as we achieved key milestones that set us up to deliver strong growth and value creation in 2024 and beyond.

謝謝，斯科特，大家下午好。 2024 年對 Ascendis 來說是有利的一年，因為我們實現了關鍵的里程碑，為我們在 2024 年及以後實現強勁成長和價值創造奠定了基礎。

With SKYTROFA firmly established as a high-value growth hormone brand in 2024, volume grow sustainable with revenue reaching around EUR200 million on a 6.5% market share of the total growth hormone market in the US and around 45% of the total US long-acting growth hormone market based on third-party prescription data.

隨著 SKYTROFA 在 2024 年牢固確立其高價值生長激素品牌的地位，銷售將持續成長，收入將達到約 2 億歐元，占美國整個生長激素市場的 6.5%，占美國長效生長激素市場的 45% 左右（基於第三方處方數據）。

With further penetration in pediatric growth hormone deficiency and a planned commercial launch across multiple indications and countries, we expect sustained value creation for the TransCon Growth Hormone franchise in the coming year as outlined in our Vision 2030.

隨著兒童生長激素缺乏症領域的進一步滲透以及計劃在多個適應症和國家進行商業推廣，我們預計 TransCon 生長激素特許經營權在未來一年將持續創造價值，正如我們的 2030 願景中所述。

Importantly, YORVIPATH, the only FDA-approved treatment for hypoparathyroidism in adults, is now launched in the US and has already begun to establish itself as the new standard of care. Given the long-standing need for a treatment option like YORVIPATH, we are seeing significant early demand in both the patient and physician communities. And we are pleased with the pace of payer approval so far. The large global population living with a significant hypopara disease burden underscores the potential for YORVIPATH to grow into a multibillion-dollar product over time.

重要的是，YORVIPATH 是唯一獲得 FDA 批准的治療成人副甲狀腺功能減退症的藥物，目前已在美國上市，並已開始成為新的治療標準。鑑於對 YORVIPATH 等治療方案的長期需求，我們看到患者和醫生群體都有很大的早期需求。到目前為止，我們對付款人批准的速度感到滿意。全球大量人口患有嚴重的副甲狀腺功能減退症，這凸顯了 YORVIPATH 隨著時間的推移發展成為價值數十億美元的產品的潛力。

Rounding out our endocrine rare disease portfolio. TransCon CNP clinical data demonstrated it could be a highly differentiated product with a unique profile that represent a major step forward in the treatment of achondroplasia and other growth disorder. We believe that once-weekly TransCon CNP data demonstrating superior linear growth and benefits beyond linear growth, supporting our proposed label for treatment of achondroplasia.

完善我們的內分泌罕見疾病產品組合。TransCon CNP 臨床數據表明，它可能是一種具有獨特特性的高度差異化產品，代表軟骨發育不全和其他生長障礙治療方面邁出了一大步。我們相信，每週一次的 TransCon CNP 數據展示了優越的線性生長和超越線性生長的益處，支持我們提出的治療軟骨發育不全的標籤。

For this reason, following our pre-NDA meeting with FDA, we are on track to submit an NDA to FDA this quarter, followed by MAA submission to the EMA in the third quarter of this year. All three of these endocrine rare disease medicine demonstrate the value of our TransCon technology platform and its potential to address major unmet medical needs with highly differentiated products.

因此，在與 FDA 舉行 NDA 前會議之後，我們將於本季向 FDA 提交 NDA，並於今年第三季向 EMA 提交 MAA。這三種內分泌罕見疾病藥物都證明了我們的 TransCon 技術平台的價值及其透過高度差異化的產品滿足重大未滿足醫療需求的潛力。

We are also bringing the TransCon technology platform beyond endocrine rare diseases in large patient population through our collaboration with Novo Nordisk in metabolic diseases such as obesity, type 2 diabetes, and cardiovascular diseases, in ophthalmology through the creation of Eyconis. We have also expanded the TransCon technology platform to incorporate protein degraders, a very promising area where we believe that new -- the new TransCon technology platform will expand our pipeline with additional potential blockbusters.

我們也透過與諾和諾德在肥胖症、2 型糖尿病和心血管疾病等代謝性疾病領域的合作，將 TransCon 技術平台推廣到廣大患者群體的內分泌罕見疾病領域，並透過創建 Eyconis 將其推廣到眼科領域。我們還擴展了 TransCon 技術平台，將蛋白質降解劑納入其中，這是一個非常有前景的領域，我們相信新的 TransCon 技術平台將擴大我們的產品線，帶來更多潛在的重磅炸彈。

We entered 2025 with a very strong financial position with a cash of EUR665 million on our balance sheet, including the $100 million upfront payment that we received from Novo Nordisk last month. As a result, we are in a strong position to invest in commercial uptake and new product development to drive continued revenue growth.

進入 2025 年，我們的財務狀況非常強勁，資產負債表上有 6.65 億歐元的現金，其中包括上個月從諾和諾德收到的 1 億美元預付款。因此，我們有能力投資商業應用和新產品開發，以推動持續的收入成長。

Let me review our key programs in rare endocrine disease in more detail. In the US, SKYTROFA was launched just over three years ago. Today, it's the treatment of choice and at the same time, growing the growth hormone market. Importantly, with the pediatric growth hormone deficiency indication alone, we are currently addressing only half of the existing US growth hormone market. Both are on path to expand SKYTROFA's addressable market in multiple ways.

讓我更詳細地回顧一下我們在罕見內分泌疾病方面的關鍵項目。在美國，SKYTROFA 於三年前推出。如今，它已成為一種首選治療方法，同時也推動了生長激素市場的不斷增長。重要的是，僅就兒童生長激素缺乏症適應症而言，我們目前僅佔現有美國生長激素市場的一半。兩家公司都在以多種方式擴大 SKYTROFA 的潛在市場。

Near term, we expect US approval in adult growth hormone deficiency this year with our PDUFA date on July 27. Longer term, we will investigate SKYTROFA in additional therapeutic areas through a basket trial, including idiopathic short stature, SHOX deficiency, Turner syndrome, and SGA.

近期，我們預計美國將於今年批准成人生長激素缺乏症治療，PDUFA 日期為 7 月 27 日。從長遠來看，我們將透過一攬子試驗研究 SKYTROFA 在其他治療領域的應用，包括特發性矮小症、SHOX 缺乏症、特納氏症和 SGA。

In the third quarter of this year, we plan to submit an IND application for this basket trial to the US FDA. Planned commercial launches across multiple countries. In 2024, SKYTROFA volume increased 84% in the United States with premium net pricing of 3x compared to once-daily growth hormone. SKYTROFA achieved revenue of around EUR200 million in 2024, supporting the potential for it to become a blockbuster product over time.

今年第三季度，我們計劃向美國FDA提交該籃子試驗的IND申請。計劃在多個國家進行商業發布。2024 年，SKYTROFA 在美國的銷售量成長了 84%，其溢價淨價是每日一次的生長激素的 3 倍。SKYTROFA 在 2024 年實現了約 2 億歐元的收入，這為其日後成為暢銷產品的潛力提供了支持。

Moving to YORVIPATH. 2024 was a critical year for YORVIPATH with commercial availability in Europe starting early in 2024 and then this past December in the US. With YORVIPATH also available to named patient programs, patients in multiple continents living with hypoparathyroidism can begin to assess this long-awaited treatment option.

移至 YORVIPATH。 2024 年對 YORVIPATH 來說是關鍵的一年，該技術將於 2024 年初在歐洲開始商業化，並於去年 12 月在美國開始商業化。YORVIPATH 也適用於指定患者計劃，多個大洲患有副甲狀腺功能減退症的患者可以開始評估這種期待已久的治療選擇。

Hypoparathyroidism represent a large global market opportunity for Ascendis to address a major unmet medical need for an effective and well-tolerated treatment option. To create durable, long-term leadership for YORVIPATH, we are building this market by educating physicians about the well-documented limits on risk of conventional therapy and the clinical benefit seen with our PTH treatment.

副甲狀腺功能減退症為 Ascendis 提供了一個巨大的全球市場機會，可以滿足對有效且耐受性良好的治療方案這一重大未滿足的醫療需求。為了使 YORVIPATH 建立持久、長期的領導地位，我們正在透過向醫生宣傳傳統療法風險的有據可查的限制以及我們的 PTH 治療所見的臨床益處來建立這個市場。

In the US, we estimate there is about 70,000 to 90,000 patients with chronic hypoparathyroidism, most of whom are currently using conventional therapy of oral calcium and active vitamin D. Our claims analysis demonstrate that 10,000 to 15,000 of these US patients are uncontrolled and 30,000 to 35,000 are partly controlled. We believe YORVIPATH can sustain growth over a long time as the vast majority of patients with hypoparathyroidism qualify for PTH treatment per the current international guidelines.

在美國，我們估計大約有 70,000 到 90,000 名慢性副甲狀腺功能減退症患者，其中大多數目前正在接受口服鈣和活性維生素 D 的常規治療。我們的索賠分析表明，其中 10,000 到 15,000 名美國患者未得到控制，30,000 到 35,000 名患者得到部分控制。我們相信 YORVIPATH 能夠長期維持成長，因為絕大多數甲狀旁腺功能減退症患者都符合現行國際指引規定的 PTH 治療條件。

Less than two months in the US YORVIPATH launched, initial demand is strong with 908 patients with prescriptions as of February 7, 2025. This includes prescription for 539 unique prescribers in around 44 states. Nearly 80% of the enrollments are new to YORVIPATH, the majority of whom are switching from conventional therapy, with the remaining being existing patients from the TransCon PTH clinical trial or expanded access program.

YORVIPATH 在美國推出不到兩個月，初期需求強勁，截至 2025 年 2 月 7 日，已有 908 名患者開立處方。這包括大約 44 個州的 539 名獨特處方者的處方。近 80% 的入組患者都是 YORVIPATH 的新患者，其中大多數是從傳統療法轉入的，其餘患者則是來自 TransCon PTH 臨床試驗或擴展獲取計劃的現有患者。

Discussion with payers are ongoing. And as expected, with a novel specialty product, we estimate the majority of insurance approval will take about four to eight weeks. We are pleased with the initial pace of insurance approval across commercial and government payers and have shipped reimbursed drug to patients in around 35 states.

正在與付款人討論。正如預期的那樣，對於一種新型專業產品，我們估計大多數保險批准將需要大約四到八週的時間。我們對商業和政府付款人的保險批准的初步速度感到滿意，並已將報銷藥品運送給大約 35 個州的患者。

Outside US, we remain on track for decent commercial launches in what we call Europe Direct countries, where we expect to add five or more countries this year. We also expect launches in multiple international markets in 2025, further expanding our global reach where we have signed eight exclusive distribution agreements covering 50-plus countries so far.

在美國以外，我們仍在所謂的歐洲直銷國家進行良好的商業發布，我們預計今年將增加五個或更多國家。我們也預計在 2025 年在多個國際市場推出產品，進一步擴大我們的全球影響力，迄今為止我們已簽署了覆蓋 50 多個國家的八項獨家分銷協議。

YORVIPATH is a unique product. Our broad and extensive clinical data include three successful Phase 3 trials in the US, Europe, Japan and China, covering diverse disease groups, including post-surgery, autoimmune, ADH1, idiopathic hypoparathyroidism. Last year, we presented three years data from our Phase 2 PaTH Forward trial. And later this year, we plan to present four years data demonstrating excellent patient retention and sustained serum calcium control and bone health, sustained reduction of calcium phosphate product independent from conventional therapy and normalization of 24-hour urinary calcium secretion. The data also showed sustained improvement in kidney function.

YORVIPATH 是一款獨特的產品。我們廣泛而全面的臨床數據包括在美國、歐洲、日本和中國進行的三項成功的 3 期試驗，涵蓋多種疾病組，包括術後、自體免疫、ADH1、特發性副甲狀腺功能減退症。去年，我們展示了第二階段 PaTH Forward 試驗的三年數據。今年晚些時候，我們計劃展示四年的數據，證明患者保留率高、血清鈣控制和骨骼健康持續改善、不依賴常規療法持續降低磷酸鈣產品、24 小時尿鈣分泌正常化。數據也顯示腎功能持續改善。

Switching to TransCon CNP. Achondroplasia remains a disease with high unmet medical need, and we believe TransCon CNP has the potential to be a highly differentiated treatment option. In the pivotal ApproaCH trial, TransCon CNP demonstrated significant improvements in linear growth and body proportionality compared to placebo as well as benefit beyond linear growth.

切換到 TransCon CNP。軟骨發育不全仍然是一種醫療需求尚未滿足的疾病，我們相信 TransCon CNP 有可能成為高度差異化的治療選擇。在關鍵的 ApproaCH 試驗中，與安慰劑相比，TransCon CNP 表現出線性生長和身體比例的顯著改善，並且具有超越線性生長的益處。

As one example of benefits beyond linear growth, we have shown data demonstrating significant improvement with TransCon CNP treatment on leg bowing, a common and debilitating complication in achondroplasia that can result in pain, impaired physical function, need for corrective surgery, and a negative impact on quality of life. TransCon CNP has shown a safety and tolerability profile comparable to placebo with low frequency of injector site reaction, all of which were mild, and no evidence of hypotension effect, supporting TransCon CNP potential as a best-in-class treatment for achondroplasia.

作為線性生長之外的益處的一個例子，我們已經展示了數據，證明 TransCon CNP 治療對腿部彎曲有顯著改善，腿部彎曲是軟骨發育不全的常見且使人衰弱的併發症，可能導致疼痛、身體功能受損、需要矯正手術以及對生活品質產生負面影響。TransCon CNP 顯示出與安慰劑相當的安全性和耐受性，注射部位反應發生率低且均為輕微反應，且無低血壓效應的證據，支持 TransCon CNP 成為治療軟骨發育不全的最佳療法的潛力。

Following our productive pre-NDA meeting with FDA, we plan to submit an NDA for the treatment of achondroplasia during the first quarter of 2025 and submit an MAA for treatment of children with achondroplasia to the EMA during the third quarter of 2025. We believe TransCon CNP will be setting a new bar for treatment of achondroplasia. To further raise this bar for linear growth and other clinical benefit, we are also working on a combination treatment of TransCon CNP and TransCon Growth Hormone in achondroplasia.

在與 FDA 舉行富有成效的 NDA 前會議之後，我們計劃在 2025 年第一季提交用於治療軟骨發育不全的 NDA，並在 2025 年第三季向 EMA 提交用於治療兒童軟骨發育不全的 MAA。我們相信 TransCon CNP 將為軟骨發育不全的治療樹立新的標準。為了進一步提高線性生長和其他臨床益處的標準，我們也正在研究 TransCon CNP 和 TransCon 生長激素對軟骨發育不全的聯合治療。

Ascendis is uniquely positioned to bring these two once-weekly medicines together in a combination treatment, providing two different modes of action to potentially improve outcome in achondroplasia and other growth disorder. We look forward to sharing top line week 26 results from Phase 2 COACH trial of TransCon CNP in combination with TransCon Growth Hormone, which we expect in the second quarter of 2025. Additionally, during the fourth quarter of 2025, we plan to submit an IND or similar to investigate TransCon CNP alone or and in combination with TransCon Growth Hormone for the treatment of hypochondroplasia.

Ascendis 的獨特優勢在於將這兩種每週一次的藥物結合在一起進行聯合治療，提供兩種不同的作用模式，從而有可能改善軟骨發育不全和其他生長障礙的治療效果。我們期待分享 TransCon CNP 與 TransCon 生長激素聯合使用的第 2 階段 COACH 試驗第 26 週的頂線結果，預計在 2025 年第二季完成。此外，在 2025 年第四季度，我們計劃提交 IND 或類似申請，以研究單獨使用 TransCon CNP 或與 TransCon 生長激素聯合使用 TransCon CNP 治療軟骨發育不全。

Looking to how we are expanding our pipeline in endocrine rare disease. We are expanding into additional product candidates beyond our first three successful medicines as we disclosed at the JPMorgan conference. In addition, we continue to broaden the reach of our platform outside endocrine rare disease and through collaboration in therapeutic area affecting much greater patient number.

看看我們如何擴大內分泌罕見疾病領域的研發管道。正如我們在摩根大通會議上所揭露的那樣，除了前三種成功的藥物之外，我們還在拓展其他候選產品。此外，我們繼續擴大我們平台在內分泌罕見疾病之外的覆蓋範圍，並透過在治療領域的合作來影響更多的患者。

For oncology, our internal development continues to focus on TransCon IL-2 beta/gamma aiming for accelerated approval in one or more indication. In early '24, we announced the formation of Eyconis to explore the development of TransCon-based therapies in ophthalmology. In November, we announced a multiproduct collaboration with Novo Nordisk covering metabolic and cardiovascular diseases with a lead program to develop once-monthly TransCon semaglutide. This entitled us to escalating tiered mid-single-digit royalties on global net sales of approved products.

對於腫瘤學，我們的內部開發繼續專注於 TransCon IL-2 beta/gamma，旨在加速獲得一種或多種適應症的批准。24 年初，我們宣布成立 Eyconis，以探索基於 TransCon 的眼科療法的發展。11 月，我們宣布與 Novo Nordisk 進行一項涵蓋代謝和心血管疾病的多產品合作，其中一項主導計畫是開發每月一次的 TransCon 司美格魯肽。這使我們有權對獲批產品的全球淨銷售額收取逐步增加的中等個位數的分級特許權使用費。

Finally, as I mentioned earlier, we have expanded TransCon to incorporate protein degraders, a technology with very promising potential within as well as outside rare endocrine diseases. Ascendis today, with approved commercial product, a strong pipeline and guided by our values of patient, science and passion, is positioned to continue driving rapid and sustained growth in the years ahead.

最後，正如我之前提到的，我們擴展了 TransCon 以納入蛋白質降解劑，這是一項在罕見內分泌疾病內外都具有非常廣闊前景的技術。如今，Ascendis 擁有已獲批准的商業產品和強大的產品線，並以患者、科學和熱情的價值觀為指導，預計將在未來幾年繼續推動快速持續的成長。

I will now turn it over to Scott Smith.

現在我將把發言權交給史考特史密斯。

Thanks, Jan Mikkelsen. The progress we made in 2024 enables us to head into 2025 with the financial and organizational strength to execute on our strategic priorities, which are: to successfully launch YORVIPATH on a global basis, to build on SKYTROFA's leadership position in pediatric GHD by expanding the US label to adults while maintaining its premium net pricing of 3x compared to daily growth hormone, and to submit TransCon CNP for approval to treat achondroplasia in children in the US and the EU. I will touch on some key points surrounding our fourth quarter and full year financial results, but for further details, please refer to our 20-F filed today.

謝謝，Jan Mikkelsen。我們在 2024 年取得的進展使我們能夠在邁入 2025 年時擁有足夠的財務和組織實力來執行我們的戰略重點，這些戰略重點是：在全球成功推出 YORVIPATH、通過將美國標籤擴展到成人來鞏固 SKYTROFA 在兒科 GHD 領域的領導地位，同時保持其與每日生長激素相比 3 倍。我將談及我們第四季度和全年財務業績的一些關鍵點，但有關更多詳細信息，請參閱我們今天提交的 20-F。

SKYTROFA volume increased 37% in the fourth quarter of 2024 compared to the fourth quarter last year, while reported revenue was EUR58.5 million compared to EUR64.2 million reported in the fourth quarter of 2023. In the fourth quarter this year, SKYTROFA revenue benefited from volume growth and a favorable sales adjustment of EUR4.6 million attributable to periods prior to January 1, 2024, which was offset by higher sales deductions compared to the same period the prior year.

2024 年第四季度，SKYTROFA 的銷量與去年第四季相比成長了 37%，報告的營收為 5,850 萬歐元，而 2023 年第四季報告的營收為 6,420 萬歐元。今年第四季度，SKYTROFA 的收入受益於銷售成長以及 2024 年 1 月 1 日之前期間的 460 萬歐元有利銷售調整，但與去年同期相比，銷售額扣除額有所增加，抵消了這一影響。

Backing out this favorable sales adjustment, SKYTROFA revenue was approximately EUR54 million for the quarter. Sequentially, SKYTROFA volume increased 16% in Q4 compared to Q3, while pricing was stable. We expect revenue growth to continue to track closer to script growth unless payer mix changes substantially as there have been no major contracting changes compared to Q4 last year.

扣除此有利的銷售調整後，SKYTROFA 本季營收約為 5,400 萬歐元。與第三季相比，SKYTROFA 第四季的銷量成長了 16%，而價格保持穩定。我們預計營收成長將繼續接近劇本成長，除非付款人組合發生重大變化，因為與去年第四季相比沒有發生重大合約變化。

Shifting to YORVIPATH. As previously reported, fourth quarter YORVIPATH revenue increased to EUR13.6 million, bringing total 2024 revenue to EUR28.7 million. As Jan noted, the launch of YORVIPATH in Germany and Austria in 2024, together with the initial demand in progress with reimbursement in the US so far in 2025, has been very encouraging. We expect that YORVIPATH will have a significant impact on our financial profile in 2025.

轉向 YORVIPATH。如前所述，YORVIPATH 第四季營收增至 1,360 萬歐元，使 2024 年總收入達到 2,870 萬歐元。正如 Jan 所指出的，YORVIPATH 將於 2024 年在德國和奧地利推出，加上 2025 年迄今在美國正在進行的初始需求和報銷，這些都非常令人鼓舞。我們預計 YORVIPATH 將對我們 2025 年的財務狀況產生重大影響。

While it is early in the launch, we look forward to sharing data on parameters like enrollments, prescribing HCPs, time to reimbursement, et cetera, to provide more detail on launch dynamics. More importantly, everything we are seeing in the early launch phase supports our view that over time, we expect YORVIPATH to be the standard of care for patients with hypoparathyroidism and to become a multibillion-dollar product.

雖然還處於發布初期，但我們期待分享有關註冊人數、處方 HCP、報銷時間等參數的數據，以提供有關發布動態的更多詳細資訊。更重要的是，我們在早期發布階段看到的一切都支持我們的觀點，即隨著時間的推移，我們預計 YORVIPATH 將成為甲狀旁腺功能減退症患者的護理標準，並成為價值數十億美元的產品。

Closing off the top line. Total revenue for the fourth quarter was EUR173.9 million, including revenue recognition of the $100 million upfront fee related to our collaboration with Novo Nordisk as well as other revenue from partners. To be clear, although we recognize the $100 million from Novo in 2024 for accounting purposes, the cash was received after year-end in January. Total revenue for the full year 2024 was EUR363.6 million.

關閉頂線。第四季總收入為1.739億歐元，其中包括與諾和諾德合作確認的1億美元預付費用以及來自合作夥伴的其他收入。需要明確的是，儘管我們出於會計目的確認了 2024 年 Novo 的 1 億美元，但這筆現金是在 1 月年末之後收到的。2024 年全年總收入為 3.636 億歐元。

Turning to expenses. For the fourth quarter, R&D costs totaled EUR79.3 million compared to EUR90.9 million during the fourth quarter of 2023. The 13% decline was largely due to lower external development costs for TransCon Growth Hormone and TransCon PTH as well as the Eyconis spin-off.

談到費用。第四季研發成本總計 7,930 萬歐元，而 2023 年第四季為 9,090 萬歐元。13% 的下降主要是由於 TransCon 生長激素和 TransCon PTH 的外部開發成本降低以及 Eyconis 的分拆。

SG&A expenses in the fourth quarter of 2024 totaled EUR80.2 million compared to EUR64 million during the fourth quarter of 2023. The EUR16 million increase was due to higher employee costs, including the impact of additional headcount supporting global commercial expansion, most of which came toward the end of the year. Similarly, we spent more on external commercial costs to support launch activities and plan to continue to do so in 2025 with the global launches of YORVIPATH.

2024 年第四季的銷售、一般及行政費用總計 8,020 萬歐元，而 2023 年第四季為 6,400 萬歐元。1600 萬歐元的成長是由於員工成本的增加，包括支持全球商業擴張的額外員工的影響，其中大部分是在年底發生的。同樣，我們在外部商業成本上花費了更多資金來支持發射活動，並計劃在 2025 年繼續這樣做，同時在全球推出 YORVIPATH。

Total operating expenses were EUR159.5 million for the fourth quarter of 2024, a 3% increase compared to EUR154.9 million during the fourth quarter of 2023. Total operating expenses for the full year 2024 were EUR598 million.

2024 年第四季總營運費用為 1.595 億歐元，較 2023 年第四季的 1.549 億歐元成長 3%。2024 年全年總營運費用為 5.98 億歐元。

Net cash financial expenses for the full year 2024 were less than EUR1 million, while net finance expenses for the full year were EUR74.4 million, driven primarily by noncash items. We ended 2024 with cash, cash equivalents and marketable securities totaling EUR560 million compared to EUR399 million as of December 31, 2023, including the $100 million upfront payment from Novo Nordisk that was received in January 2025. Cash at the end of '24 would have totaled EUR655 million.

2024 年全年淨現金財務支出不到 100 萬歐元，而全年淨財務支出為 7,440 萬歐元，主要由非現金項目推動。截至 2024 年，我們的現金、現金等價物和有價證券總額為 5.6 億歐元，而截至 2023 年 12 月 31 日為 3.99 億歐元，其中包括 2025 年 1 月收到的來自諾和諾德的 1 億美元預付款。24 年底的現金總額將達到 6.55 億歐元。

Finally, as separately announced, we expect to use approximately $25 million in the first quarter of 2025 to preserve approximately 200,000 ADSs held as treasury shares.

最後，正如單獨宣布的那樣，我們預計將在 2025 年第一季使用約 2500 萬美元來保留作為庫存股持有的約 200,000 股 ADS。

With that, operator, we are now ready to take questions.

接線員，現在我們可以回答問題了。

(Operator Instructions) Jessica Fye, JPMorgan.

（操作員指示） Jessica Fye，摩根大通。

Hey, guys. Good afternoon. Thanks for taking my question and congrats on the strong YORVIPATH script number and breadth of subscribers. I have one question with a few parts, mostly just confirming some stuff. First, can you confirm that the 908 figure is unique patients and not like cumulative scripts including refills, for example?

嘿，大家好。午安.感謝您回答我的問題，並祝賀 YORVIPATH 腳本數量和訂閱者範圍的廣泛。我有一個包含幾個部分的問題，主要只是確認一些事情。首先，您能否確認 908 這個數字是單獨的患者，而不是包括續藥在內的累積處方？

Second, can you just confirm how many of the EAP and OLE rollover patients are now included in that 908 number? I want to make sure I heard you. I think you said it was 84% new to YORVIPATH, 16% from the EAP and OLE.

其次，您能否確認現在有多少 EAP 和 OLE 延期病患包含在 908 個數字中？我想確認我聽到你的聲音了。我認為您說過 84% 是 YORVIPATH 的新成員，16% 是來自 EAP 和 OLE 的成員。

Lastly, I think you reiterated that you continue to expect the majority of insurance approvals will take four to eight weeks. Can you just confirm that's actually what you're seeing now that you've been in the US market for coming up on eight weeks? Thank you.

最後，我認為您重申過，您仍然預計大多數保險批准將需要四到八週的時間。您能否確認這確實是您進入美國市場八週以來所看到的情況？謝謝。

Thanks, Jess, a lot for the questions. I think we can confirm nearly all the answers. So Jay and Sherrie, will you confirm all the numbers, just to be sure?

非常感謝傑西提出這些問題。我想我們幾乎可以確認所有答案。那麼 Jay 和 Sherrie，為了確保萬無一失，你們能確認一下所有的數字嗎？

Happy to. Jessica, thank you for the question. The first part of your question, from an enrollment standpoint, we can confirm that is unique patient enrollments, so not cumulative repeat.

很開心。傑西卡，謝謝你的提問。您問題的第一部分，從招生的角度來看，我們可以確認這是獨特的患者招生，因此不是累積重複。

I think the second question you asked was the percentage of patients that are coming over from either the EAP or clinical trials versus those that are new to YORVIPATH. So about 20% of the 908 is existing patients from TransCon PTH EAP or clinical trials and then 80% of patients are actually new to YORVIPATH.

我認為您問的第二個問題是來自 EAP 或臨床試驗的患者與 YORVIPATH 新患者的比例。因此，這 908 名患者中約有 20% 是來自 TransCon PTH EAP 或臨床試驗的現有患者，而 80% 的患者實際上是 YORVIPATH 的新患者。

And then the third question that I think we heard you ask, Jessica, is more around the four to eight weeks. That is our estimate of what we think it should take. But keep in mind, too, that based on the timeframe for which the drug has been on market, it is still a very nascent period of time where, for many of the patients enrolled, that time period hasn't actually occurred yet, right? So we'll need more time to get a better sense of that, but that is our initial estimate today.

潔西卡，我想我們聽到您問的第三個問題是關於四到八週的時間。這是我們對應該採取的措施的估計。但也請記住，根據該藥物上市的時間範圍，這仍是一個非常初期的時期，對於許多參與研究的患者來說，這個時期實際上還沒有到來，對嗎？因此我們需要更多時間來更好地了解這一點，但這是我們今天的初步估計。

Thank you. For my follow-up, can you provide the YORVIPATH patient number outside the US?

謝謝。為了我的後續治療，您能提供美國境外的 YORVIPATH 患者編號嗎？

We have not broken that number down. It's still increasing as we expected to do. We are still only in Europe Direct countries, full commercial in Germany and Austria. We have our AP2 program in France, a nonpromotional program that also is enrolling reimbursed patients and then we have our international market in this way. And the patient numbers are increasing to exactly as we have expected, but we have not broken down the numbers.

我們還沒有詳細分析這個數字。正如我們預期的那樣，它仍在增長。我們仍然只在歐洲直銷國家開展業務，在德國和奧地利進行全面商業化。我們在法國有 AP2 計劃，這是一項非促銷計劃，也招募報銷患者，然後我們透過這種方式進入國際市場。患者人數正在增加，正如我們預期的那樣，但我們還沒有對具體數字進行細分。

Tazeen Ahmad, Bank of America.

美國銀行的塔津·艾哈邁德（Tazeen Ahmad）。

Hi, guys. Good afternoon and thanks for taking my questions. Jan, could you provide any color on how many of the 908 scripts that have been written have now been converted to patients on actual therapy? And can you give us also any color that you might have on what proportion of these patients may have had previous experience with NATPARA? And then I have a follow up.

嗨，大家好。下午好，感謝您回答我的問題。Jan，您能否透露一下，在已開立的 908 份處方中，有多少已經轉化為接受實際治療的患者？您能否告訴我們，這些患者中有多少人曾經使用過 NATPARA？然後我有一個後續行動。

Yeah. The question you are addressing is a question where we still lack all the information to give you and really the concrete answer that you want to have. What we have done in our market research, we have looked a lot on claim data. And we have defined patient group, which we call the 10,000 to 15,000 patients, which we will call not controlled on standard therapy or conventional therapy, and this patient group is basically seeing the physician at least 4 times a year. And they also will have one thing more in common.

是的。對於您所提出的問題，我們仍然缺乏所有資訊來提供給您，也無法給出您真正想要得到的具體答案。我們在市場調查中所做的就是大量查看索賠數據。我們已經定義了患者群體，我們稱之為 10,000 到 15,000 名患者，我們稱其為未接受標準療法或常規療法控制的患者，該患者群體基本上每年至少看醫生 4 次。而且他們還會有一個共同點。

They have at least one hospitalization related to the disease. And we also know the limitation in really -- that is in seeing an endo. So out from that perspective, just by the random process when you can see an endo, we actually believe that many of the patients that we see of the 908 actually are coming from the group which we define as more uncontrolled in this. We don't have a positive definition if that is true or not, but that is all expectation in this.

他們至少有一次因該疾病住院的經驗。我們也知道真正的限制——那就是看到內視鏡。因此從這個角度來看，僅通過隨機過程，當您看到內視鏡檢查時，我們實際上相信我們看到的 908 名患者中的許多人實際上來自我們定義為更不受控制的群體。我們無法肯定這是否屬實，但這只是我們的期望。

The second question you raised about how many patients we have on therapy now is a number we are waiting, some way, to come out with until we feeling we have sufficient, good enough data to give you a solid number because we are now in the initial part of our, you can say, journey of getting them 100% reimbursed.

您提出的第二個問題是，我們現在有多少患者正在接受治療，我們正在等待這個數字的公佈，直到我們覺得我們有足夠多、足夠好的數據來給您一個確切的數字，因為我們現在正處於讓他們 100% 報銷的初始階段。

We were extremely positive on the broadness of having reimbursed patients, both from the commercial setup but also for the government side. And we basically are getting reimbursed patient every place from. And when you see the broadness on the state, we're covering with about 35 different states, we're really coming out in all different states.

我們對向患者提供報銷的廣泛性持非常積極的態度，無論是從商業角度還是從政府角度。我們基本上從各個地方獲得病人的報銷。當您看到州的廣度時，您會發現我們的覆蓋範圍已覆蓋了大約 35 個不同的州，我們實際上已經涵蓋了所有不同的州。

We're also feeling that we are in a very, very strong position. The vast majority of the patients are on label. And basically, they are also fulfilling exactly the criteria that justifies for them to be on a PTH treatment. So we are really highly positive on the development we have seen in the reimbursement spectrum.

我們也感覺到我們處於非常非常有利的地位。絕大多數患者都符合標籤要求。基本上，他們也完全符合接受 PTH 治療的標準。因此，我們對報銷範圍內的發展非常樂觀。

Okay. Thanks, Jan. And then I just wanted to clarify, I think you had said that you were considering providing sales guidance for YORVIPATH for the full year sometime in the middle of the year. Does that -- still the plan?

好的。謝謝，Jan。然後我只想澄清一下，我認為你曾說過你正在考慮在年中某個時候為 YORVIPATH 提供全年銷售指導。這還是計劃嗎？

I think -- Tazeen, I think we would like to give you guidance when we believe in the numbers. And I think that is the criteria we take up. So depending on how we see the numbers going and how we see different regions, we will come up with what we call revenue guidance exactly when we're feeling that we feel a bit confident.

我認為——塔澤恩，當我們相信這些數字時，我想我們會給你指導。我認為這就是我們採取的標準。因此，根據我們對數位趨勢的看法以及對不同地區的看法，當我們感到有點信心時，我們會提出所謂的收入指導。

Scott always like to give up a lot of numbers. So you can hear in his list and what he said in the prepared remarks that he will come up with a lot of elements that can give you the best possible fundament to build up a solid model in your own way.

斯科特總是喜歡放棄很多數字。因此，您可以從他的清單和他在準備好的演講中聽到，他將提出許多元素，為您提供最好的基礎，以便您以自己的方式構建可靠的模型。

Comment from you, Scott?

斯科特，您有何評論？

Yeah. We will -- as we said, we're excited to continue to share with you the underlying parameters driving the launch, and we plan to do that in the quarters ahead.

是的。正如我們所說，我們很高興繼續與大家分享推動此次發布的潛在參數，我們計劃在未來幾季內做到這一點。

Gavin Clark-Gartner, Evercore ISI.

Gavin Clark-Gartner，Evercore ISI。

Congrats on the very strong progress so far. Just had one question on YORVIPATH and one on CNP. For YORVIPATH, how have your discussions with payers gone so far? And what are your assumptions for how some of the prior authorization criteria may read? Specifically wondering if you think it's going to be different than the label. And kind of on that same line, maybe you could just remind us your contracting or gross to net assumptions. That's the first one.

祝賀迄今為止的巨大進展。我剛剛對 YORVIPATH 和 CNP 分別有一個疑問。對於 YORVIPATH，您與付款人的討論進度如何？您對某些事先授權標準有何假設？具體來說，想知道您是否認為它會與標籤不同。並且在同一條線上，也許您可以提醒我們您的承包或總額到淨額的假設。這是第一個。

On the CNP side, for the CNP plus growth hormone combo data coming in the second quarter, can you just remind us your expectations, specifically on AGV? Thank you.

在 CNP 方面，對於第二季即將發布的 CNP 加生長激素組合數據，您能否提醒我們您的預期，特別是對 AGV 的預期？謝謝。

Yeah. I think Jay will come with some flavor about the contracting situation. But also, as I said before, I've been lucky to see most of the UN criteria. And I have been really pleased how they are aligning to the labeling. But I believe Jay will come up with comments related to the commercial contracting landscape.

是的。我認為傑伊會對簽約情況有所了解。但正如我之前所說，我很幸運地看到了大部分聯合國標準。我真的很高興他們能夠與標籤保持一致。但我相信傑伊會提出與商業承包情勢相關的評論。

Yeah. So thank you for the question. As you can expect for any new launch, we are still in the early stages of establishing policy with payers. So just as an example, most medical policies right now for our large national players haven't even published a policy yet, right? So our conversations have all been productive to date, really focusing on the clinical value proposition of the drug. As you can see and based on our data from our array of clinical studies, we feel really positive about the benefit that we can convey to the patient community, and we're having great conversation around that.

是的。謝謝你的提問。正如您對任何新產品的預期一樣，我們仍處於與付款人制定政策的早期階段。舉個例子，目前我們全國性大型保險公司的大多數醫療保險政策甚至還沒有發布，對嗎？因此，到目前為止，我們的對話都是富有成效的，真正集中在藥物的臨床價值主張。正如您所看到的，根據我們一系列臨床研究的數據，我們對能夠為患者群體帶來的益處感到非常樂觀，並且我們正在就此進行深入的討論。

Specifically, your question around prior auths and what that might look like, we're expecting and, again, as part of those negotiations and discussions, wanting to ensure that the standard PA is consistent to label, both in terms of reauthorization timelines, tests that may need to be conducted to ensure that, again, it is consistent with label. So while many of those plans and policies still need to take some time to come into fruition, we're feeling encouraged by those conversations.

具體來說，您關於先前授權的問題以及它可能是什麼樣子，我們期待並且再次作為這些談判和討論的一部分，希望確保標準 PA 與標籤一致，無論是在重新授權時間表方面，還是可能需要進行的測試，以確保它與標籤一致。因此，儘管許多計劃和政策仍需要一段時間才能實現，但這些對話讓我們感到鼓舞。

So the CNP question is always looking in the crystal ball because you asked me, Jan, what is your expectation to data you have not really seen? And it's the first time, to my knowledge, everyone have done a combination trial in achondroplasia, a Phase 2 trial, between TransCon CNP and Growth Hormone.

因此，CNP 問題總是透過水晶球來預測，因為你問我，Jan，你對你還沒有真正看到的數據有什麼期望？據我所知，這是第一次大家對軟骨發育不全進行 TransCon CNP 和生長激素的聯合試驗，即第 2 階段試驗。

And why I think it's really, really interesting because it's two different compounds become very different physiological mode of action. And if I ever believe in science, which I always do a lot, it should be a great combination because it's synergistic pathway.

我認為這真的非常有趣，因為兩種不同的化合物具有非常不同的生理作用模式。如果我相信科學，而我一直都相信科學，那麼這應該是一個很好的組合，因為它是一種協同途徑。

And when I look on what you can do when you address the hyperactive tyrosine kinase systems that you have in achondroplasia, you can do that with either the tyrosine kinase inhibitors, you can do it by CNP as short-acting or, you can say, continuous exposure.

當我研究如何治療軟骨發育不全症中過度活躍的酪胺酸激酶系統時，我發現可以使用酪胺酸激酶抑制劑，也可以使用 CNP 作為短效藥物，或者也可以說，持續給藥。

I think it's easier to saturate the annualized height velocity in this part of the integrated effect you expect to give as a treatment option in achondroplasia. One of them that's easiest to hit is basically the annualized height velocity.

我認為，在您期望作為軟骨發育不全的治療選擇提供的綜合效果的這一部分中，使年化身高增長速度飽和更容易。其中最容易實現的指標基本上就是年化身高速度。

And when I look on all the data, it's likely are going around 5.5 to 6.0 on analyzed height velocity, which basically are reflecting a little bit what the science also will say, you are moving a brake, and you restore normal growth. So out from that perspective.

當我查看所有數據時，分析出的身高速度可能在 5.5 到 6.0 左右，這基本上反映了科學所說的，即踩下煞車，恢復正常生長。從這個角度來看。

And this is why I love the growth hormone, because what is growth hormone? This is like sitting in a car and then you suddenly get rid of the speeder. Some may take a little bit on the speeder, get the brake off, and then you really can move. And this is why I feel this combination will give good results. And I look forward to the results as much. I can ask you, what would a good result be, Gavin?

這就是我喜歡生長激素的原因，因為生長激素是什麼？這就像坐在車裡，然後你突然擺脫了超速行駛的人。有些人可能會稍微加速一點，然後放開煞車，然後你就可以真正移動了。這就是為什麼我認為這種組合會產生良好的效果。我同樣期待結果。我可以問你，加文，什麼才是好的結果？

That's helpful. Thanks, guys. We'll leave it there for now.

這很有幫助。謝謝大家。我們暫時把它留在那裡。

Li Watsek, Cantor Fitzgerald.

李沃特塞克，康托費茲傑拉。

Wanted to add my congrats on the strong YORVIPATH launch as well. Just curious, for these 900-plus prescriptions, what proportion of these patients have more severe versus more moderate diseases? And if you can share any early trends of compliance and initial titration, whether it's consistent with your clinical trials.

我也想對 YORVIPATH 的強勢發布表示祝賀。只是好奇，對於這 900 多張處方，這些患者中患有較嚴重疾病的患者佔多大比例，患有較輕微疾病的患者佔多大比例？並且您是否可以分享任何早期依從性和初始滴定趨勢，是否與您的臨床試驗一致。

Yes. It's a question we tried to address with before. But I think, Sherrie, you're also sitting with a lot of data. Potentially, you can, in some way, describe the limitation that we have in our dataset. We need to answer that question today.

是的。這是我們之前嘗試解決的問題。但我認為，謝麗，你也掌握了大量數據。您可能可以以某種方式描述我們資料集中的限制。我們今天需要回答這個問題。

Sure. And thanks for the question, Li. So what -- we don't actually have data in terms of the enrollments on patient severity. What we do know though is a couple of important things. One is that, as Jan said earlier, the most severe patients are going most frequently to the endocrinologists. So by that practical matter of them getting into the office to get the prescription, it's likely that we have severe patients initially getting some of the first prescriptions.

當然。謝謝李先生的提問。那麼——我們實際上沒有關於患者嚴重程度的登記數據。但我們確實知道一些重要的事情。一是，如 Jan 之前所說，病情最嚴重的病人最常去看內分泌科。因此，從他們到辦公室取處方的實際情況來看，很可能重症患者最初會得到一些首批處方。

And as Jan also mentioned, there are a number of those uncontrolled patients in the US. There's 10,000 to 15,000 of them and then a number more of people who are partially controlled. So to the extent that we are starting to see some of the first patients being the more uncontrolled and severe patients, we know there's still a tremendous amount of room for expansion beyond that.

正如 Jan 所提到的，美國有許多不受控制的患者。他們有 10,000 到 15,000 人，還有更多的人受到部分控制。因此，當我們開始看到一些首批患者是病情更加不受控制和更加嚴重的患者時，我們知道除此之外還有巨大的擴展空間。

Thanks, Sherrie.

謝謝，謝麗。

Thank you.

謝謝。

Derek Archila, Wells Fargo.

富國銀行的德里克‧阿奇拉 (Derek Archila)。

This is Eva on for Derek. Thanks for taking our questions and congrats on the progress. A quick one from us on YORVIPATH. So can you provide some color on what type of docs are prescribing YORVIPATH? Are these like high-volume docs? Or are you starting to get some docs from the community?

這是 Eva 為 Derek 表演的。感謝您回答我們的問題，並祝賀取得的進展。我們在 YORVIPATH 上快速介紹了一下。那麼您能否提供一些關於哪些類型的文件正在開出 YORVIPATH 的詳細資訊？這些像大容量文件嗎？或者您是否開始從社區獲取一些文件？

And as a follow-up, how long do you expect patients will take to convert from drug in the EAP over to paid drug? Thanks.

作為後續問題，您預計患者需要多長時間才能從 EAP 藥物轉換為付費藥物？謝謝。

Yeah. Let me take the last question before I turn it over to Jay or Sherrie. What is happening in our EAP program, the last packet they got was a three-pack of basic three months, and some of them got them in December to -- and January. So the 100-plus patients that we are converting from our EAP clinical trial over will likely come into commercial drug starting in February and then the majority in March. So that was the second question.

是的。在將問題交給傑伊或謝麗之前，請容許我回答最後一個問題。我們的 EAP 計劃中發生的情況是，他們收到的最後一包是三個月的基本三包，其中一些人在 12 月到 1 月收到了它們。因此，我們從 EAP 臨床試驗中轉化的 100 多名患者可能會從 2 月開始服用商業藥物，然後大多數患者將在 3 月開始服用。這是第二個問題。

And I think -- Sherrie or Jay, who will take the -- will you start, Jay?

我認為——Sherrie 或 Jay，誰會接手——你會先開始嗎，Jay？

Sure. Happy to start. I think the question around prescriber breadth, I think, as we mentioned before, 539 across 44 states. We're seeing that pretty broadly across all different types of physicians across all deciles. Naturally, you would expect directionally physicians that are treating perhaps a greater number of patients, right?

當然。很高興開始。我認為有關處方廣度的問題，正如我們之前提到的，44 個州有 539 個。我們在各個十分位數的所有不同類型的醫生中都廣泛地看到了這一點。自然，您會期望定向醫生能夠治療更多的患者，對嗎？

We're naturally also focusing on them quite heavily. So from a field standpoint, we're actually over 50% reach for a lot of our priority physicians. So I think naturally, you're going to see some directional lean in that direction. But more importantly, what you're seeing is a broad outreach and broad interest across the provider community, agnostic of decile.

我們自然也非常關注它們。因此，從現場角度來看，我們的許多重點醫生的覆蓋率實際上已經超過 50%。因此我認為，你自然會看到朝這個方向的一些傾向。但更重要的是，您所看到的是整個提供者社群的廣泛影響和廣泛興趣，與十分位數無關。

And maybe I'll just add to that, that what is really exciting is that we see that we're broadening a lot beyond the NATPARA prescribers. So of the 539 physicians, only about 200, a little less than 200 had prescribed NATPARA. So we see that we're really broadening our reach.

也許我只是想補充一點，真正令人興奮的是，我們看到我們正在遠遠超出 NATPARA 處方者的範圍。因此，在 539 名醫生中，只有大約 200 名（略少於 200 名）開設了 NATPARA。因此，我們看到我們確實正在擴大我們的影響力。

Yaron Werber, TD Cowen.

Yaron Werber，TD Cowen。

Great. So thanks so much. I got maybe a couple of questions, Scott, for you. And then I don't know, Jan, if you want to take the next one. I think, Scott, you said that towards the end of the year, you could be -- you could reach profitability on a cash basis. Does that still sort of hold? And what would drive that? How do we -- is it going to be YORVIPATH is the biggest driver?

偉大的。非常感謝。史考特，我有幾個問題想問你。然後我不知道 Jan，你是否想參加下一個節目。史考特，我認為你說過，到今年年底，你就能夠實現現金獲利。這種說法還成立嗎？是什麼推動了這項進程？我們如何－YORVIPATH 會成為最大的驅動力嗎？

And then secondly, as you think about reimbursement for YORVIPATH, are you expecting, with time, prior authorizations? Or are you expecting not to have any prior auths? Thank you.

其次，當您考慮 YORVIPATH 的報銷時，您是否期望隨著時間的推移獲得事先授權？或者您預計不會有任何先前的授權？謝謝。

Okay. I think Scott would like to say something.

好的。我認為斯科特想說些什麼。

Yeah. I think you're exactly right. YORVIPATH will be a big driver of the ability to cash breakeven. It's a strong launch in Europe for us. Obviously, we're off to the races here in the US. And it's a very profitable product. So I think we agree that, that will be a strong driver of breakeven potential this year.

是的。我認為你說得完全正確。YORVIPATH 將成為實現現金損益平衡能力的重要推手。對我們來說，這是在歐洲的強勢亮相。顯然，我們已經在美國開始參加比賽了。這是一種非常有利可圖的產品。所以我認為我們都同意，這將成為今年實現盈虧平衡潛力的強大推動力。

Yeah. But I also believe you need to look that US is the numbers we're giving you today. But we basically have a global effort. And we also are, some way, seeing that end of this year, we're starting to take into a much, much higher gear in our Europe Direct countries.

是的。但我也相信你需要看看我們今天給你的數字。但我們基本上是全球性的努力。而且，我們也看到，從今年底開始，我們在歐洲直銷國家的業務將進入更高的發展階段。

We also see the international market is starting to really, really get engaged. I expect that it will be a major event for '26 where all the countries will come in mainly with full year launches in -- for many of them, but '25 will be where we start in both the Europe Direct in at least five countries more but basically also our international market.

我們也看到國際市場開始真正參與其中。我預計這將是 2026 年的一件大事，屆時所有國家都將參與其中，其中許多國家將在全年推出新產品，但 2025 年將是我們在至少五個國家直接進入歐洲市場的起點，基本上也是我們國際市場的起點。

So the US, sure, is a fast market, is a fast penetration we can get because it's so large single market. So sure, it will dominate in the beginning of the year. But just remember, the number of patients outside the US with hypopara is so much, much, much larger, perhaps four, fivefold than what you have in the US.

因此，美國確實是一個快速市場，我們可以快速滲透，因為它的單一市場非常大。所以可以肯定的是，它將在年初佔據主導地位。但請記住，美國以外患有副甲狀腺功能減退症的患者數量要多得多，可能是美國的四到五倍。

The second one, will you take that, Jay?

第二個，傑伊，你願意接受嗎？

Yeah. Sure. I mean from a prior auth standpoint, I think the question was what do we expect for YORVIPATH. It is a specialty product, and I anticipate there to be some basic questions, even if it's as simple as who's prescribing it, right? I think -- whether it's an endocrinologist, whether it's a nephrologist, et cetera.

是的。當然。我的意思是，從先前授權的角度來看，我認為問題是我們對 YORVIPATH 有什麼期望。這是一種特殊產品，我預計會有一些基本問題，即使像誰開的處方這麼簡單，對嗎？我認為——無論是內分泌科醫生，還是腎臟科醫生等等。

And I think secondly, what you're going to see and should expect is there's going to be wide heterogeneity across what you'll see across both national and regional plans. I think as we alluded to before, we are seeing approvals across commercial payers, public payers. And even absent of there being a formalized policy at some of the large national payers, we still submit generic prior auths to seek exception through that policy. So again, some of this will take time to evolve and some of that we would expect to change. But we will see probably a wide range across the various plans.

其次，我認為你將會看到並且應該預料到的是，國家和地區計劃之間將存在很大的差異。我認為，正如我們之前提到的，我們看到了商業付款人和公共付款人的批准。即使一些大型國家付款機構沒有正式的政策，我們仍然會提交通用的事先授權，以透過該政策尋求例外。所以，有些方面需要時間來發展，而有些方面我們預期會改變。但我們可能會看到各種計劃之間存在著廣泛的差異。

Joseph Schwartz, Leerink.

約瑟夫·施瓦茨，Leerink。

Hi. I'm Joori Park dialing in for Joe. Thank you for taking our questions. I believe in the last earnings conference call, you mentioned that in Germany, physicians are prescribing YORVIPATH to about one to two of their patients, whereas in the US, you are expecting physicians to prescribe the drug to two to three of their patients. And based on the metrics that you provided today, it seems like on average, each physician is prescribing the drug to a little over 1.5 of their patients. So I was just wondering if you're still expecting each physician in the US to prescribe YORVIPATH to about two to three of their patients. And where does it go from there?

你好。我是喬裡·帕克 (Joori Park)，代喬接線。感謝您回答我們的問題。我相信在上次收益電話會議上，您提到在德國，醫生會給大約一到兩名患者開 YORVIPATH 處方，而在美國，您預計醫生會給兩到三名患者開這種藥。根據您今天提供的指標，似乎平均每位醫生都會為 1.5 名以上的患者開立這種藥物。所以我只是想知道您是否仍然期望美國每位醫生為大約兩到三名患者開出 YORVIPATH 處方。那麼它接下來會去哪裡呢？

Yeah. I think in some way, I accept what I said, and I stand by what I said before. And I think the pattern we see now is an early launch. I have seen and follow some of the physicians that was part of our EAP and clinical trial. And one -- some of these physicians have been already making prescription up to 20 patients.

是的。我想在某種程度上，我接受我所說的話，我堅持我之前所說的話。我認為我們現在看到的模式是早期推出。我見過並跟隨一些參與我們 EAP 和臨床試驗的醫生。其中有些醫生已經為多達 20 名患者開出了處方。

So no doubt the broadness of that will come. But in some way, this is in early launch, one to two months in the launch. So I will expect that to see and come in the future.

因此，毫無疑問，這一範圍將會擴大。但從某種程度上來說，這還處於早期發布階段，發布後一到兩個月。所以我期待未來能夠看到並實現這一點。

Okay. Great. That's helpful. And then a clarifying question. Are there any -- are any of the 908 prescriptions included in the YORVIPATH sales from 2024, considering the drug was available mid to late December? Thank you so much.

好的。偉大的。這很有幫助。然後是一個澄清問題。考慮到該藥物在 12 月中下旬上市，從 2024 年開始，YORVIPATH 銷售中是否包含 908 張處方？太感謝了。

Scott?

史考特？

I mean strictly speaking -- so we did ship a very small amount in December. It was basically immaterial to the total.

我的意思是嚴格來說——我們在 12 月確實發貨了非常少量的貨物。這對於總數來說基本上無關緊要。

Yeah. So in practical, no.

是的。所以實際上，不是。

Kelly Shi, Jefferies.

傑富瑞 (Jefferies) 的凱莉施 (Kelly Shi)。

Congrats on the great quarter. On manufacturing front, how should we think about the capacity to meet the increasing demand of YORVIPATH throughout the year? Thank you.

恭喜本季取得如此出色的成績。在製造業方面，我們應該如何考慮滿足 YORVIPATH 全年不斷增長的需求的能力？謝謝。

Yeah. I think one of the things we have been very, very proud at Ascendis is really our robust supply chain. We have seen how we have managed to go up in high demand on the shortage of the daily growth hormone and could fulfill all requirement for all [issues] for having, for example, the SKYTROFA brand.

是的。我認為 Ascendis 最引以為傲的事情之一就是我們強大的供應鏈。我們已經看到，我們如何設法滿足日常生長激素短缺的高需求，並能夠滿足所有[問題]的所有要求，例如 SKYTROFA 品牌。

And when I look on the YORVIPATH, we're using the same solid supply chains, the same infrastructure. We followed the same way. I personally get a weekly report on every compound in every region, in every place where we are selling product, how many months there is on storage. And we, some way, are taking that as a really serious thing because we will never be in a position that we will go short. And that is our vision, and I hope we never come to this positioning.

當我查看 YORVIPATH 時，我們發現我們使用相同的穩固供應鏈和相同的基礎設施。我們也照樣做。我個人每週都會收到一份報告，內容涉及每個地區、每個銷售產品的地方的每種化合物，以及儲存時間。在某種程度上，我們非常重視這一點，因為我們永遠不會陷入做空的境地。這就是我們的願景，我希望我們永遠不會陷入這種境地。

Thank you.

謝謝。

Ellie Merle, UBS.

瑞銀的艾莉·梅爾（Ellie Merle）。

Hey, guys. Thanks so much for taking the question and congrats on the launch progress. Just in terms of how we should think about the US YORVIPATH script cadence, I guess, sort of what's the latest that you're seeing in terms of the cadence of new starts? Are you sort of seeing a steady number of ask each week? Was there a bolus upfront? How should we think about this going forward?

嘿，大家好。非常感謝您提出這個問題，並祝賀發布進展順利。就我們應該如何看待美國 YORVIPATH 腳本節奏而言，我想，就新開始的節奏而言，您所看到的最新情況是什麼？您是否看到每週的詢問數量保持穩定？預先有推注嗎？我們今後該如何看待這個問題？

And second, just a follow-up on reimbursement. I know you said you're seeing approvals across a number of plans. But could you characterize maybe sort of the number of scripts that have been covered so far and sort of any trends that you're seeing in terms of ease of reimbursement, say, between the moderate patients versus the severe patients and your expectations there? Thanks.

第二，只是對報銷進行跟進。我知道您說過您看到許多計劃都獲得了批准。但是，您能否描述一下迄今為止已涵蓋的處方數量，以及您在報銷便利性方面看到的任何趨勢，例如中度患者與重度患者之間的趨勢，以及您的預期？謝謝。

I think the question related to what we call controlled to partly controlled and -- patient, we have, in some way, answered this to our best of knowledge. We have no clear data of the patients that is -- already have received a prescription. We have a gut feeling, and the gut feeling is that we believe many of them belong to the uncontrolled part because they see the endo in a much higher frequence than anyone else.

我認為這個問題與我們所說的控製到部分控制有關——耐心，我們已經以某種方式盡我們所知回答了這個問題。我們沒有已經收到處方的患者的明確數據。我們有一種直覺，這種直覺就是，我們相信他們中的許多人屬於不受控制的部分，因為他們看到內視鏡的頻率比任何人都高得多。

Related to the pattern on prescription, we are not breaking it down in weeks or anything. This is something we are following [where we are tight]. And we would like to see a pattern being developed. We don't believe there's really a huge bolus coming in because there is not a huge availability of the (inaudible) really to come in and say, oh, I just want to have an appointment, run into an endo and now we have a prescription. It's not like (inaudible).

關於處方模式，我們不會按週或其他時間分解。這是我們正在關注的事情[我們處境緊張]我們希望看到一種模式正在形成。我們不相信真的有大量的推注藥進來，因為沒有大量的（聽不清楚）真的進來並說，哦，我只是想預約，遇到一位內分泌科醫生，現在我們有處方。這不像（聽不清楚）。

Like Aimee is sitting here. If you want to see Aimee, our CMO, at Stanford, it takes how many weeks now, Aimee?

就像艾米坐在這裡一樣。如果你想在史丹佛見到我們的行銷長艾米，現在需要多少週呢，艾米？

12.

12.

12 weeks to see her. So it takes a little bit of time to get an appointment. So we don't believe that it's a lot of built-up demand. It's patients that come in and have the need to be in a treatment. And I think it's pretty obvious for me, when I see the benefit that all the patient gets, everyone should have a treatment option and come on PTH like everyone on type 1 diabetes should have insulin. This is a hormone replacement therapy in this perspective.

12週後才能見到她。因此預約需要一點時間。所以我們不認為這是一個很大的累積需求。病人來這裡是為了接受治療。我認為這對我來說非常明顯，當我看到所有患者都獲得的好處時，每個人都應該有一種治療選擇並使用 PTH，就像每個 1 型糖尿病患者都應該使用胰島素一樣。從這個角度來看，這是一種荷爾蒙替代療法。

Related to the reimbursement system, I do not know, Jay, if you have further comments compared to that.

關於報銷制度，傑伊，我不知道您是否還有進一步的評論。

Yeah. As we mentioned before, because this is such early days, I don't think we would be able to draw a meaningful pattern or trend based on just a few weeks that we've been in here. I think I go back to the statement we made before. We are seeing approvals across all -- both commercial and public payers, but fully recognizing too that because many policies aren't in place, a lot of these cases are exception-by-exception basis. And we believe that after at least a few more months, we'll have a better sense of how these policies shake out and what that more stable trend should be.

是的。正如我們之前提到的，由於現在還處於早期階段，我認為我們無法僅根據幾週的情況得出有意義的模式或趨勢。我想回到我們之前所作的聲明。我們看到商業和公共付款人都給予了批准，但我們也充分認識到，由於許多政策尚未到位，許多此類案例都是個別例外。我們相信，至少再過幾個月，我們就會更了解這些政策將如何發揮作用，以及更穩定的趨勢應該是什麼樣子。

Great. Thanks.

偉大的。謝謝。

David Lebowitz, Citi.

花旗銀行的 David Lebowitz。

Thank you for taking my question. First, on SKYTROFA, you had the PDUFA date coming up this summer for the adult growth hormone deficiency. I'm just curious, how should we be thinking about that in terms of what that market opportunity actually presents?

感謝您回答我的問題。首先，關於 SKYTROFA，成人生長激素缺乏症的 PDUFA 日期是今年夏天。我只是好奇，我們該如何看待這個市場機會實際上帶來的問題？

Yeah. I think Aimee can explain on the unmet medical need that really exists in adult growth hormone deficiency. From my perspective, there's two key things I really -- some way, are reflecting over a lot. First of all, it's an area with extremely low penetration. To our best knowledge, it's under 5%, 6%, 7%.

是的。我認為艾米可以解釋成人生長激素缺乏症真正存在的未滿足的醫療需求。從我的角度來看，有兩件關鍵的事情我確實在以某種方式反思。首先，這是一個滲透率極低的領域。據我們所知，這一比例低於 5%、6%、7%。

So you can say there is a huge opportunity for growth. And the other thing is that has been a huge burden basically, to be in the treatment with daily growth hormone. But Aimee, you can explain and tell about what is really the unmet medical need, the burden of having adult growth hormone deficiency.

因此可以說，這是一個巨大的成長機會。另一件事是，每天使用生長激素治療基本上是一個巨大的負擔。但是艾米，你可以解釋一下真正未滿足的醫療需求，即成人生長激素缺乏症的負擔。

Sure. Happy to do so. So many people arrive at growth hormone deficiency in adulthood following something involving organically the brain, right, so a brain tumor or brain cancer or its treatment, either surgery or radiation. That's at least 50% or more. So many of them, because they are missing function of the pituitary gland, are taking many hormone replacements. And growth hormone is just one on that list.

當然。很高興這麼做。許多人成年後會因大腦有機問題而出現生長激素缺乏症，也就是腦瘤或腦癌，或透過手術或放射治療進行治療。這至少是50%或更多。他們中的許多人由於缺乏腦下垂體功能而服用多種荷爾蒙替代品。生長激素只是其中的一種。

So they have oftentimes said, if I -- if it's something we can make simpler, right, that the community could provide more simply to them, they would -- it is something they would consider, knowing that it adds to their metabolic health and overall endocrine health, right? But of course, their first priority always are the two lifesaving hormones from the brain, that is from the adrenal gland and the thyroid gland. So those you can't forget, and those are pills.

所以他們經常說，如果我——如果我們可以把某件事做得更簡單，對吧，社區可以更簡單地為他們提供，他們會——這是他們會考慮的事情，因為他們知道這有益於他們的代謝健康和整體內分泌健康，對吧？但當然，他們的首要任務始終是來自大腦的兩種救命激素，也就是來自腎上腺和甲狀腺的激素。所以那些你不能忘記，那些是藥丸。

So after that, they are willing to think about injectable, less frequent therapies, knowing it is good for their overall health. We could admit that growth hormone deficiency is not immediately life-threatening the way that if you don't take thyroid or adrenal replacement is. So we think we're in a nice sweet spot here. If it's hormone that should be replaced and if it meets patients' expectations, we think there would be taken.

因此，在那之後，他們願意考慮注射、頻率較低的療法，因為他們知道這對他們的整體健康有益。我們可以承認，生長激素缺乏症不會像不服用甲狀腺或腎上腺替代藥物那樣立即危及生命。因此我們認為我們目前處於一個很好的最佳位置。如果需要替換的是激素，並且如果它符合患者的期望，我們認為就會採取這種措施。

Thank you for that. And just jumping over to YORVIPATH. I'm just curious as to thoughts on potential competing pivotal data coming out this year and how you think the market ultimately might evolve.

謝謝你。然後直接跳到 YORVIPATH。我只是好奇您對今年可能出現的關鍵競爭數據的看法，以及您認為市場最終會如何發展。

Yeah. If you reflect on pivotal data, I don't think there is anyone else than one compound, the amyloid compound. And to our best knowledge, when we talked with centers, their last patient in was in the beginning of November. So I'm still waiting to see the results of the pivotal trial. It's a small trial with a little bit more than 100 patients.

是的。如果你反思關鍵數據，我認為除了澱粉樣蛋白化合物之外沒有其他化合物。據我們所知，當我們與各中心交談時，他們的最後一位患者是在 11 月初。所以我仍在等待關鍵試驗的結果。這是一項小型試驗，只有 100 多名患者參與。

So it shouldn't take too long time to clean the data and come up with the top line data. But I have not seen anything else. When I go back to the science at one of our key values, this is not a hormone replacement therapy. This is a substitution of the long-acting effect where you basically are placing part of the receptor system into a fixed position and therefore, have a long-acting effect. It's not even reflecting the normal biology where you are basically activating both the PTH 1 receptor and the PTH 2 receptor.

因此，清理資料並得出頂線資料應該不會花費太長時間。但我沒有看到其他任何東西。當我回顧我們的一個核心價值時，我發現這並不是荷爾蒙替代療法。這是長效效應的替代，基本上是將部分受體系統置於固定位置，因此具有長效效應。它甚至沒有反映正常的生物學特性，即基本上同時激活 PTH 1 受體和 PTH 2 受體。

And by doing the different mode of action, you already are -- from the data, can see that it can now substitute, as in hormone replacement therapy, element on where you see it's not restoring normal function, for example, in the kidney, both with -- for example, related to phosphate excretion. See, for example, it cannot lower a key element like calcium phosphate complex. You also see the unnatural activation to the activating system in the bone and other organs. And then I'm not talking about the hemogenic potential that is in the compound. So we are looking forward to see the data.

透過採取不同的作用方式，您已經可以從數據中看到，它現在可以替代激素替代療法中無法恢復正常功能的元素，例如在腎臟中，兩者都與磷酸鹽排泄有關。例如，它不能降低磷酸鈣複合物等關鍵元素。您還會看到骨骼和其他器官中的活化系統的非自然活化。然後，我並不是說化合物的造血潛力。所以我們期待看到數據。

We would like to see the data, and we hope one day that will come out. They should be out there now because it's so long time since the last patient came into the visit.

我們希望看到這些數據，並希望有一天這些數據能夠出來。他們現在應該在那裡，因為距離上一位病人來診已經過去很久了。

Paul Choi, Goldman Sachs.

高盛的保羅·崔（Paul Choi）。

Hi. Thanks. Good afternoon and congrats on the early launch success with YORVIPATH in the US. My first question is on YORVIPATH. And as we look at consensus numbers, The street is modeling less than 900 patients in the US for this year. And you've already exceeded that in terms of scripts. So I was just wondering, recognizing that you're not giving guidance and not -- and the reimbursement is a work in progress, just your level of comfort with The street, a revenue number for the full year possibly, or any color around that would be great.

你好。謝謝。下午好，恭喜 YORVIPATH 在美國早期成功推出。我的第一個問題是關於 YORVIPATH 的。當我們查看一致數據時，我們發現今年美國的患者數量不到 900 名。就劇本而言，你已經超越了這一點。所以我只是想知道，認識到你沒有給出指導，而且報銷是一項正在進行的工作，只是你對街道的舒適程度，可能是全年的收入數字，或者任何相關的顏色都會很棒。

And my second question is regarding CNP and the hypochondroplasia program that you plan to file an IND for later this year. Are you planning to do any run-in activities ahead of that possibly at some of the centers just to potentially help accelerate the timing of that study and enrollment? Any color there would be helpful. Thank you very much.

我的第二個問題是關於 CNP 和軟骨發育不全項目，您計劃在今年稍後為其提交 IND。您是否計劃在某些中心提前進行一些準備活動，以便可能有助於加快該研究和招生的時間？任何顏色都會有幫助。非常感謝。

Yeah. Let me take the first part together with Aimee because we are really dedicated to be the leader in growth disorder. And when we see the two cornerstones we have, TransCon Growth Hormone and TransCon CNP, we really will do the best for the patient in each case. How can we design an optimal treatment in this way?

是的。讓我和 Aimee 一起進行第一部分，因為我們真的致力於成為成長障礙領域的領導者。當我們看到我們擁有的兩大基石——TransCon 生長激素和 TransCon CNP 時，我們確實會在每種情況下為患者提供最佳的治療。我們如何以這種方式設計最佳治療方法？

And what we're doing now in hypochondroplasia is design what is really the pathway forward for us. Is it then just a TransCon CNP treatment? Or will it be a combination treatment between TransCon CNP and TransCon Growth Hormone? And we are now in a position that we are starting the discussion with regulatory agencies.

我們現在針對軟骨發育不全所做的工作是設計出真正適合我們前進的道路。那麼它只是一種 TransCon CNP 治療嗎？或者它是 TransCon CNP 和 TransCon 生長激素的聯合治療？現在我們正開始與監管機構進行討論。

But I think Aimee can give you a little bit of background why we, some way, think that when we're moving into hypochondroplasia, it's one of many growth disorders we actually would like to focus on. And the actual design can also be a different state process.

但我認為艾米可以給你一些背景信息，說明為什麼我們認為當我們討論軟骨發育不全時，它是我們實際上想要關注的眾多生長障礙之一。而實際的設計也可以是不同狀態的過程。

So exactly. We are taking the time to give hypochondroplasia the opportunity it deserves. While some of hypochondroplasia overlaps highly with achondroplasia and the genetic variant arises on the same FGFR3 receptor, the gene changes are very different along that whole receptor. And we are understanding that hypochondroplasia has a unique phenotype. It's a broader phenotype and very unique.

確實如此。我們正在花時間為軟骨發育不良症提供應有的機會。雖然部分軟骨發育不全與軟骨發育不全高度重疊，且遺傳變異出現在相同的 FGFR3 受體上，但整個受體上的基因變化卻非常不同。我們正在了解軟骨發育不良具有獨特的表型。這是一種更廣泛的表型並且非常獨特。

So along those lines, we are still figuring out -- it's an active process, what's the population of interest to us, where we can benefit from them, and therefore, the different ways to find a regulatory path forward, which I think gets to your question about how much time do we put in into the run in.

因此，沿著這些思路，我們仍在弄清楚——這是一個積極的過程，我們感興趣的人群是什麼，我們可以從他們身上獲得什麼好處，因此，我們要找到不同的監管途徑，我認為這可以回答你的問題，即我們投入了多少時間。

So I couldn't tell you now as we are still figuring a lot of this out. But I think the condition and other conditions of short stature, especially on the skeletal dysplasia genetics side, right, deserve a very good, thorough understanding to find the best way to accomplish.

所以我現在無法告訴你，因為我們仍在解決很多問題。但我認為身材矮小症以及其他病症，特別是骨骼發育不良的遺傳方面，值得進行非常透徹的了解，以找到最佳的治療方法。

And we are in this position that potentially we will start both trials at the same time, CNP and then combination trial. And then we will basically evaluate the data and find out that potentially we will go for an approval for both. And then they can choose the optimal treatment from the physician, how they best can serve the patient needs in this way. If they really want to have a much more extensive linear growth, likely, the combination therapy will be the preferred option.

我們目前的情況是，我們可能會同時啟動兩項試驗，即 CNP 試驗和組合試驗。然後，我們將對數據進行基本評估，並發現我們有可能同時獲得這兩項批准。然後他們可以從醫生那裡選擇最佳治療方法，以便最好地滿足患者的需求。如果他們確實希望獲得更廣泛的線性增長，那麼聯合療法可能是首選方案。

Related to your last -- first question, I think we said in Scott's prepared remarks that we are not giving any guidance, as you correctly said. We would like to give you as much as possible what we can call elements we are using in our own modeling and giving that as fast as we can give it with all the different goals to ensuring that you have the best possible modeling that you can do. And I think Scott is always open for discussion. He's extremely extroverted, like to talk with people. So I think if there is any element of model discussion, I think he likely will engage in it.

關於您的最後一個問題，我想我們在斯科特的準備好的演講中說過，我們不會提供任何指導，正如您正確指出的那樣。我們希望盡可能多地向您提供我們在自己的建模中使用的元素，並儘快提供這些元素，以實現不同的目標，以確保您擁有盡可能最好的建模。我認為史考特總是願意接受討論。他非常外向，喜歡與人交談。因此我認為如果有任何模型討論的元素，我認為他可能會參與其中。

Alex Thompson, Stifel.

亞歷克斯·湯普森（Alex Thompson），Stifel。

Hey. Great. Thanks for taking my questions. I guess on YORVIPATH, I wonder if you could talk a little bit about how titration is working in the real world with patients, whether that requires additional visits with their HCP, et cetera, if this is done at home. And then maybe could you talk a little bit about your expectations around gross to net stability in 2025 for SKYTROFA? Thanks.

嘿。偉大的。感謝您回答我的問題。我想在 YORVIPATH 上，我想知道您是否可以稍微談談滴定在現實世界中對患者的作用，如果在家中進行滴定，是否需要與他們的 HCP 進行額外訪問等等。然後，您能否談談您對 2025 年 SKYTROFA 的整體穩定性和淨穩定性的期望？謝謝。

Aimee, would you take the first?

艾米，你會選第一個嗎？

Sure. The first question was about titrations with YORVIPATH. From what we've heard so far, right, this is in the domain -- this is the sweet spot for endocrinologists. They know how to titrate medicine. So we are -- but that being said, I'm not sitting on the shoulder of each prescriber, and I can't see what they're doing week to week.

當然。第一個問題是關於使用 YORVIPATH 進行滴定。從我們目前所聽到的來看，這是該領域——這是內分泌學家的最佳領域。他們知道如何滴定藥物。所以我們是——但話雖如此，我並沒有站在每個開處方者的立場上，我也看不到他們每週都在做什麼。

I think so far, they have found it straightforward to follow. They have gotten the guidance that they wanted. And the only times we may have touch points with them will be as we go further along and one switches from the medium-dose pen to a high-dose pen or a low-dose pen. But we don't have that insight yet. But from what we're hearing just anecdotally, it's what endocrinologists know how to do.

我認為到目前為止，他們已經發現它很容易遵循。他們已經得到了他們想要的指導。我們與他們唯一的接觸點就是隨著我們進一步發展，從中劑量筆換成高劑量筆或低劑量筆。但我們還沒有這樣的見解。但從我們聽到的傳聞來看，這是內分泌學家知道如何做到的。

At least what we have seen now by being in market in Germany for one year now, we are not seeing any issues to the titration and patient-physician feel that is not complicated and easy element to do it. And they're getting up on conventional therapy exactly at the same speed that we saw in our clinical trials, which surprised me a little that they were doing in the same speed as we do when we have much more regional framework for a patient to come into and talk with the physician. It's same thing happening in real life. They're out of conventional therapy extremely fast.

至少從我們在德國市場進入一年來的情況來看，我們沒有看到滴定方面有任何問題，患者和醫生都感覺這不是什麼複雜且容易做到的因素。他們在常規療法上的進步速度與我們在臨床試驗中看到的速度完全相同，這讓我有點驚訝，因為我們有更區域性的框架，可以讓患者來這裡與醫生交談，但他們的進步速度與我們一樣快。現實生活中也發生同樣的事情。他們很快就擺脫了傳統療法。

Yun Zhong, Wedbush Securities.

韋德布希證券公司的雲鐘。

Excuse me. Good afternoon. Thank you very much for taking the questions. The first one on YORVIPATH. So when you report first quarter earnings, are you going to break down sales to tell us how much is coming from Europe, how much is from US, please?

打擾一下。午安.非常感謝您回答這些問題。YORVIPATH 上的第一個。那麼，當您報告第一季收益時，您是否會細分銷售額以告訴我們有多少來自歐洲，有多少來自美國？

That's a good question. We will decide when we come to that state exactly how we report the data.

這是個好問題。當我們達到該狀態時，我們將決定如何報告數據。

Okay. Then a follow-up question on SKYTROFA. I believe what I heard was that the adjustment has largely been over for 2024, but you haven't really given any guidance unlike in January last year, you put out the guidance for 2024. And are there any uncertainties surrounding SKYTROFA? Is that related to the adult launch or more related to the pediatric market, please?

好的。然後是關於 SKYTROFA 的後續問題。我相信我聽到的是，2024 年的調整已基本結束，但您並沒有真正給出任何指導，不像去年 1 月，您發布了 2024 年的指導。那麼，SKYTROFA 還存在哪些不確定因素呢？請問這與成人市場的推出有關還是與兒科市場更相關？

Yeah. Thanks for the question. So we expect revenue growth to continue to track closer to script growth going forward, unless, of course, there's payer mix changes -- substantial payer mix changes. And this is primarily because there's been no major contracting changes compared to last year, Q4 last year.

是的。謝謝你的提問。因此，我們預計未來收入成長將繼續接近劇本成長，除非付款人結構發生變化——付款人結構發生重大變化。這主要是因為與去年第四季相比，合約沒有發生重大變化。

That's all the time we have for questions today. This concludes today's conference call. Thank you for participating. You may now disconnect.

今天我們的提問時間就到這裡了。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。