Ascendis Pharma A/S (ASND) 2023 Q4 法說會逐字稿

Good day, and thank you for standing by. Welcome to the fourth quarter 2023 Ascendis Pharma earnings conference call. (Operator Instructions) Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Tim Lee, Senior Director of Investor Relations. Please go ahead.

美好的一天，感謝您的支持。歡迎參加 Ascendis Pharma 2023 年第四季財報電話會議。（操作員指示）請注意，今天的會議正在錄製中。現在我想將會議交給今天的第一位發言人，投資者關係高級總監 Tim Lee。請繼續。

Thank you, operator, and thank everyone for joining our full-year 2023 financial results conference call. I'm Tim Lee, Senior Director of Investor Relations at Ascendis Pharma. Joining me on the call today are Jan Mikkelsen, President and Chief Executive Officer; Scott Smith, Executive Vice President and Chief Financial Officer; Dr. Stina Singel, Executive Vice President and Head of Clinical Development, Oncology; and Joe Kelly, Senior Vice President, Head of US Commercial, Endocrinology.

謝謝運營商，也感謝大家參加我們的 2023 年全年財務業績電話會議。我是 Tim Lee，Ascendis Pharma 投資者關係資深總監。今天與我一起參加電話會議的還有總裁兼執行長 Jan Mikkelsen；史考特‧史密斯，執行副總裁兼財務長； Stina Singel 博士，執行副總裁兼腫瘤學臨床開發主管；喬·凱利（Joe Kelly），高級副總裁，美國商業內分泌主管。

Before we begin, I'd 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. Examples of such statements may include, but are not limited to, statements regarding our commercialization and continued development of SKYTROFA for the US and European markets, as well as certain financial expectations for 2024, our commercialization and development of YORVIPATH in the EU, and expected timing of the FDA review of the potential launch of TransCon PTH in the US, our pipeline candidates and our expectations with respect to their continued progress and potential commercialization, our strategic plans or goals regarding our clinical pipeline, including the timing of clinical results, are ongoing and planned regulatory filings, and our expectations regarding the timing and the result of regulatory decisions, our ability to create value in multiple therapeutic areas outside of endocrinology rare disease, our progress towards Vision 2030, and the potential success of Eyconis.

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，這些陳述旨在涵蓋《私人證券訴訟改革法案》規定的安全港。此類聲明的範例可能包括但不限於有關我們在美國和歐洲市場的 SKYTROFA 的商業化和持續開發的聲明，以及對 2024 年的某些財務預期、我們在歐盟的 YORVIPATH 的商業化和開發以及預期FDA 審查TransCon PTH 在美國上市的時間、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、我們關於臨床產品的戰略計劃或目標，包括臨床結果的時間，正在進行和計劃中的監管備案，以及我們對監管決策的時間和結果的期望，我們在內分泌罕見疾病之外的多個治療領域創造價值的能力，我們朝著Vision 2030 邁進的進展，以及Eyconis 的潛在成功。

These statements are based on information that is available to us as of today. Actual results may differ -- 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 later today, February 7, 2024.

這些陳述是基於我們今天掌握的資訊。實際結果可能有所不同—可能與我們的前瞻性聲明中的結果有重大差異，您不應過度依賴這些聲明。除非法律要求，否則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聲明部分以及今天晚些時候向 SEC 提交的 20-F 表格年度報告中的風險因素部分，2024 年 2月7 日。

For TransCon Growth Hormone or TransCon hGH is approved in the US by FDA and the EU has received MAA authorization from the European Commission for the Treatment of Pediatric Growth Hormone Deficiency. The European Commission has granted marketing authorization for TransCon PTH as a replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. 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.

對於 TransCon 生長激素或 TransCon hGH 在美國已獲得 FDA 批准，歐盟已獲得歐洲兒童生長激素缺乏症治療委員會的 MAA 授權。歐盟委員會已授予 TransCon PTH 上市許可，作為治療成人慢性副甲狀腺功能減退症的替代療法。否則，請注意我們的候選產品尚處於研究階段，尚未被批准用於商業用途。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。本次電話會議期間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'll discuss our full-year 2023 financial results and will provide further business updates, following some prepared remarks, we'll then open up the call for questions. With that, let me turn it over to Jan.

在今天的電話會議上，我們將討論 2023 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評論後，我們將開始提問。那麼，讓我把它交給簡。

Good afternoon, everyone. 2023 was a transformative year for Ascendis Pharma. We streamlined the company, including our structure, our processes, and operating expense allocation, and at the same time, we believe we are on track to achieve our vision by 2025.

大家下午好。 2023 年對 Ascendis Pharma 來說是改變的一年。我們精簡了公司，包括我們的結構、流程和營運費用分配，同時，我們相信我們預計在 2025 年實現我們的願景。

SKYTROFA is the leading growth hormone product in value in the US. The launch of YORVIPATH in Europe direct and international markets is underway beginning with Germany and Austria. And our clinical program for TransCon CNP is progressing to both pivotal data expected in Q4. We believe Ascendis is advancing to become a leading biopharma company with a strong focus on endocrinology rare diseases and capabilities to also equate value in auto therapeutic area as we do in oncology, ophthalmology, and metabolic diseases.

SKYTROFA 是美國價值領先的生長激素產品。YORVIPATH 正在歐洲直接和國際市場上推出，首先是德國和奧地利。我們的 TransCon CNP 臨床計劃正在取得預期第四季度的兩項關鍵數據。我們相信 Ascendis 正在發展成為一家領先的生物製藥公司，重點關注內分泌罕見疾病，並有能力將自身治療領域的價值與我們在腫瘤學、眼科和代謝疾病領域的價值等同起來。

Because of the decisions we took in 2023, we believe Ascendis is a leaner, more efficient organization in 2024. Well put position to fulfill our Vision 2030 with three independent endocrinology rare disease blockbuster products and expand our engine for future innovation. Now that we provide an update on these programs.

由於我們在 2023 年做出的決定，我們相信 Ascendis 在 2024 年將成為一個更精簡、更有效率的組織。憑藉三款獨立的內分泌罕見疾病重磅產品，我們有能力實現我們的 2030 年願景，並擴大我們未來創新的引擎。現在我們提供這些程式的更新。

From the beginning, we designed SKYTROFA to be best-in-class growth hormone product, by releasing unmodified somatropin. By addressing the needs of the patient, caregivers, physicians, and payers, SKYTROFA achieved US market value leadership in 2023, just two years after launch. We estimated that SKYTROFA penetration in the US pediatric growth hormone deficiency patient population was around 16% at the end of 2023. With SKYTROFA expanding the US growth hormone market to the potential of USD3 billion, we believe SKYTROFA has the potential to be a blockbuster on US revenue alone.

從一開始，我們就透過釋放未修飾的生長激素將 SKYTROFA 設計為一流的生長激素產品。透過滿足患者、護理人員、醫生和付款人的需求，SKYTROFA 於 2023 年（即推出後僅兩年）實現了美國市場價值領先地位。我們估計，到 2023 年底，SKYTROFA 在美國兒科生長激素缺乏症患者族群的滲透率約為 16%。隨著 SKYTROFA 將美國生長激素市場拓展至 30 億美元的潛力，我們相信 SKYTROFA 僅在美國收入方面就有潛力成為重磅炸彈。

Built on this value leadership, we expect our first label expansion to be adult growth hormone deficiency progress. We plan to submit a supplement BLA to the FDA in the second quarter of this year. In addition, we expect top-line data from our Phase 2 trial from Turner syndrome in the fourth quarter of 2024.

建立在這種價值領先地位的基礎上，我們預計我們的第一個標籤擴展將是成人生長激素缺乏症的進展。我們計劃在今年第二季向 FDA 提交補充 BLA。此外，我們預計特納氏症 2 期試驗的頂線數據將於 2024 年第四季公佈。

Now turning to TransCon PTH. Last week, we initiated the launch of TransCon PTH in Europe direct and international market. Market as you will be perhaps with full commercial availability in Germany and Austria at an initial list price of EUR105,000 per patient per year. An estimated 700,000 adult patient in Germany are living with chronic hypoparathyroidism, and our initial launch will target 22,000 of those.

現在轉向 TransCon PTH。上週，我們開始在歐洲直接和國際市場推出 TransCon PTH。市場如您所願，在德國和奧地利完全商業化，初始標價為每位患者每年 105,000 歐元。德國估計有 70 萬名成年患者患有慢性副甲狀腺功能減退症，我們的首次推出將針對其中 22,000 名患者。

YORVIPATH Europe direct launch is off to a great start with our first prescription and orders proceed at the first day of launch, demonstrating the seriousness of the disease and the unmet medical need. We are continuing to expand our EU direct infrastructure and expect availability of YORVIPATH across Europe by the end of 2025. In parallel to meet the needs of the patients, we plan to provide commercial reimposed product to early exit routes such as named patient programs. The US producer date for TransCon PTH is May 14. If approved, we plan to launch our YORVIPATH as quickly as possible they offer to our status US commercial infrastructure.

YORVIPATH 歐洲直接推出是一個良好的開端，我們的第一個處方和訂單在推出的第一天就開始進行，這表明了疾病的嚴重性和未滿足的醫療需求。我們正在繼續擴大我們的歐盟直接基礎設施，並預計在 2025 年底 YORVIPATH 在整個歐洲可用。在滿足患者需求的同時，我們計劃向早期退出路線（例如指定患者計劃）提供商業重新使用產品。TransCon PTH 在美國的生產日期是 5 月 14 日。如果獲得批准，我們計劃盡快啟動我們的 YORVIPATH，他們為我們提供了美國商業基礎設施的地位。

Moving now to TransCon CNP. Our clinical program is designed to support approval of TransCon CNP as a treatment for patients of all ages with our competition. TransCon CNP dose at (inaudible) per kilo per week has demonstrated superiority compared to placebo in to 52-week trials. In the open label extension, we observed expected strong patient retention of 97% for now up to four years. As a result of this unexpected finding, we continue to review our own data and scientific literature. We believe now that achondroplasia is both a growth disorder and a massive disorder.

現在轉向 TransCon CNP。我們的臨床計劃旨在支持 TransCon CNP 被批准為與我們競爭的所有年齡層患者的治療方法。在為期 52 週的試驗中，與安慰劑相比，TransCon CNP 劑量（聽不清楚）每公斤每週顯示優越性。在開放標籤擴展中，我們觀察到目前長達四年的患者保留率預計高達 97%。由於這一意外發現，我們繼續審查我們自己的數據和科學文獻。我們現在相信軟骨發育不全既是一種生長障礙，也是一種巨大的疾病。

As presented at the JPMorgan conference in January, we showed significant improvement in health and quality of life for children with achondroplasia treated with TransCon CNP compared to placebo. With this growing insight, we have designed our people across tried to be evaluate meaningful benefits related to all aspects of achondroplasia, including linear growth and improvements in comorbidity as messaged by regular endpoints, physical function, body compensation, and quality of life.

正如 1 月摩根大通會議上所介紹的那樣，我們發現，與安慰劑相比，接受 TransCon CNP 治療的軟骨發育不全兒童的健康和生活品質顯著改善。憑藉這種不斷增長的洞察力，我們設計了我們的員工，試圖評估與軟骨發育不全各個方面相關的有意義的益處，包括常規終點、身體功能、身體代償和生活品質所傳達的線性生長和合併症的改善。

We expect to see a top line data from this trial, and we plan to submit an NDA in the fourth quarter of this year. In addition, we are pursuing additional treatment opportunities in achondroplasia. Infant trials aged zero to two years; first patient already had been enrolled. Combination trial with SKYTROFA, aged two to 11, week 26, top-line annualized growth velocity in the full fourth quarter of 2024. Adult plan to file an IND or similar in the third quarter of this year.

我們預計會看到這次試驗的主要數據，並計劃在今年第四季提交 NDA。此外，我們正在尋求更多軟骨發育不全的治療機會。零至兩歲的嬰兒試驗；第一個患者已經入組。與 SKYTROFA 的聯合試驗，年齡為 2 歲至 11 歲，第 26 週，2024 年第四季的頂線年化成長率。Adult 計劃在今年第三季提交 IND 或類似文件。

Switching now to oncology. Both TransCon IL-2 beta gamma and TransCon TLR7/8 Agonist had shown favorable safety profiles and single agent clinical activity. We expect 2024 to be an extremely important year for oncology pipeline with data readout in better defined patient population in the fourth quarter. Also in the fourth quarter, we expect to have completed enrollment of our randomized Phase 2 trial in new agile with head and neck cancer.

現在轉向腫瘤學。TransCon IL-2 beta gamma 和 TransCon TLR7/8 激動劑均顯示出良好的安全性和單藥臨床活性。我們預計 2024 年對於腫瘤學管道來說將是極為重要的一年，第四季將在更明確的患者群體中讀出數據。同樣在第四季度，我們預計將完成頭頸癌新敏捷隨機 2 期試驗的註冊。

Longer term. To maximize this potential reach and value of these oncology product candidate, we aspire to commercialize our oncology cases to partnership with companies with specialized oncology experience and capability in late-stage development and commercialization.

從長遠來看。為了最大限度地發揮這些腫瘤學產品候選者的潛在影響力和價值，我們渴望將我們的腫瘤學案例商業化，與具有專業腫瘤學經驗和後期開發和商業化能力的公司合作。

Moving now to ophthalmology. We recently announced the formation and launch of an independent company, Eyconis, to develop and commercialize TransCon ophthalmology products globally. We have received an equity position in the newly formed company, and we have elected to receive development, regulatory, and sales milestones plus royalties.

現在轉向眼科。我們最近宣布成立並成立一家獨立公司 Eyconis，在全球開發和商業化 TransCon 眼科產品。我們已獲得新成立公司的股權，並選擇獲得開發、監管和銷售里程碑以及特許權使用費。

In January, we introduced Vision 2030, our strategic roadmap to achieve blockbuster status for ease of our three endocrinology rare disease products and expand our engine for future innovation. With a broad applicability of the TransCon technology platform, our goal has laid out in Vision 2030 is to apply our algorithm for product innovation to is that there's opportunities in greater than USD5 billion indication. As we did with an anti-VEGF anti-PD-1 classes where we believe we have designed the best-in-class programs. We are pleased with the interest in our once monthly GPL-1 program and from our platform technologies, we expect to continue to generate many more opportunities in the future.

一月份，我們推出了“2030 年願景”，這是我們的戰略路線圖，旨在讓我們的三種內分泌罕見疾病產品實現重磅炸彈地位，並擴大我們未來創新的引擎。憑藉 TransCon 技術平台的廣泛適用性，我們在 Vision 2030 中製定的​​目標是將我們的產品創新演算法應用於超過 50 億美元的市場機會。正如我們在抗 VEGF 抗 PD-1 類別中所做的那樣，我們相信我們已經設計了一流的項目。我們很高興大家對每月一次的 GPL-1 計劃感興趣，透過我們的平台技術，我們預計未來將繼續創造更多機會。

I will now turn the call over to Scott for financial review before we open for questions.

現在，在我們開始提問之前，我將把電話轉給史考特進行財務審查。

We continue making significant progress towards our financial goal of becoming operating cash flow breakeven on a quarterly basis by the end of 2024. I will touch on some key points surrounding our financial results, but for further details, please refer to our Form 20-F filed today.

我們持續在實現 2024 年底前實現季度營運現金流損益平衡的財務目標方面取得重大進展。我將談到有關我們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 表格。

As we previously announced in early January, SKYTROFA revenue for the fourth quarter of 2023 was EUR64.2 million compared to EUR47 million reported in the third quarter and EUR17.1 million reported in the same period last year. 37% sequential growth in SKYTROFA revenue from Q3 to Q4 was again driven primarily by strong underlying demand in the US. Total revenue for the fourth quarter was EUR137.7 million, including the one-time $70 million Teijin upfront payment recognized at EUR63.7 million of license revenue.

正如我們之前在 1 月初宣布的那樣，SKYTROFA 2023 年第四季的收入為 6,420 萬歐元，而第三季報告的收入為 4,700 萬歐元，去年同期報告的收入為 1,710 萬歐元。從第三季到第四季度，SKYTROFA 營收季增 37%，這再次主要受到美國強勁的潛在需求的推動。第四季總收入為 1.377 億歐元，其中包括帝人一次性預付款 7,000 萬美元，授權收入為 6,370 萬歐元。

Turning to expenses. R&D costs in the quarter totaled EUR19.9 million, down 18% sequentially from the third quarter of 2023, primarily driven by lower endocrinology rare disease related costs as trials and development complete and lower oncology related cost. SG&A expenses were essentially flat at EUR64 million compared to the third quarter of 2023, reflecting commercialization synergies and expense controls.

轉向開支。本季的研發成本總計 1,990 萬歐元，較 2023 年第三季季減 18%，主要是由於試驗和開發完成後內分泌罕見疾病相關成本下降以及腫瘤學相關成本下降。與 2023 年第三季相比，SG&A 費用基本持平，為 6,400 萬歐元，反映了商業化協同效應和費用控制。

Total operating expenses were EUR155 million for the fourth quarter, down 12% sequentially from the third quarter. Overall, our operating loss for the fourth quarter declined sequentially by 73% to EUR37 million from EUR134 million in the third quarter of 2023. We ended the fourth quarter with cash, cash equivalents, and marketable securities totaling EUR399 million.

第四季總營運費用為 1.55 億歐元，比第三季季減 12%。總體而言，我們第四季的營運虧損環比下降 73%，從 2023 年第三季的 1.34 億歐元降至 3,700 萬歐元。截至第四季末，我們的現金、現金等價物和有價證券總額為 3.99 億歐元。

Last month, we announced the formation launch together with an investor syndicate of Eyconis to develop, manufacture, and commercialize TransCon ophthalmology assets globally. As a result, we expect minimal, if any, P&L burden from ophthalmology in 2024. As a reference point for Q4 2023, external ophthalmology project costs totaled EUR6.4 million.

上個月，我們宣布與 Eyconis 投資者財團一起成立，以在全球開發、製造和商業化 TransCon 眼科資產。因此，我們預計 2024 年眼科的損益負擔將極小（如果有的話）。作為 2023 年第四季的參考點，外部眼科計畫成本總計 640 萬歐元。

As previously announced for the full-year 2024, based on current plans, we expect SKYTROFA revenue to be in the range of EUR320 million to EUR340 million at average 2023 exchange rates. Total operating expenses, SG&A, and R&D together to be approximately EUR600 million, and we expect to be operating cash flow breakeven on a quarterly basis by the end of 2024.

如同先前宣布的 2024 年全年，根據當前計劃，我們預計 SKYTROFA 收入將按 2023 年平均匯率計算將在 3.2 億至 3.4 億歐元之間。總營運費用、SG&A 和研發費用合計約為 6 億歐元，我們預計到 2024 年底，每季營運現金流量將達到損益兩平。

Let me now also provide a review of selected key program milestones. For TransCon Growth Hormone, we plan to submit an SBLA to FDA for adult growth hormone deficiency in the second quarter of 2024, and we expect to report top-line results from our Phase 2 Turner syndrome trial in the fourth quarter of 2024.

現在讓我回顧一下選定的關鍵計畫里程碑。對於 TransCon 生長激素，我們計劃在 2024 年第二季度向 FDA 提交成人生長激素缺乏症的 SBLA，並預計在 2024 年第四季度報告 2 期特納氏症試驗的主要結果。

For TransCon PTH in the US, our PDUFA date is May 14, 2024. If approved, we plan to launch it as YORVIPATH as quickly as possible thereafter. Outside the US, we initiated the launch last month of TransCon PTH marketed as YORVIPATH with full commercial availability in Germany and Austria. We plan to roll out YORVIPATH in our Europe direct and international markets segments throughout 2024 and 2025.

對於美國的 TransCon PTH，我們的 PDUFA 日期是 2024 年 5 月 14 日。如果獲得批准，我們計劃此後儘快將其命名為 YORVIPATH。在美國以外，我們上個月啟動了 TransCon PTH 的推出，商品名為 YORVIPATH，並在德國和奧地利全面上市。我們計劃於 2024 年和 2025 年在歐洲直接和國際市場推出 YORVIPATH。

For TransCon CNP, our clinical program evaluating TransCon CNP as a treatment for achondroplasia advances with top-line results from the pivotal approach trial and an expected NDA submission for the treatment of children with achondroplasia, both in the fourth quarter of 2024. In addition, during the fourth quarter of 2024, we expect to report week 26 top-line data from the COACH trial in combination with TransCon Growth Hormone and submit an IND or similar for adults with achondroplasia.

對於 TransCon CNP，我們評估 TransCon CNP 作為軟骨發育不全治療方法的臨床項目取得了進展，關鍵方法試驗的主要結果和預期提交的用於治療軟骨發育不全兒童的 NDA 均將於 2024 年第四季度提交。此外，在 2024 年第四季度，我們預計將報告 COACH 試驗與 TransCon 生長激素聯合使用的第 26 週頂線數據，並提交針對成人軟骨發育不全患者的 IND 或類似數據。

Within our oncology therapeutic area, we plan to provide a clinical update from indication specific dose expansion cohorts in the I'll Believe and transcendIT trials during the fourth quarter. In addition, we expect to complete enrollment of our randomized Phase 2 trial in neoadjuvant head and neck cancer.

在我們的腫瘤治療領域，我們計劃在第四季度提供 I'll Believe 和 transcendIT 試驗中適應症特定劑量擴展隊列的臨床更新。此外，我們預計將完成新輔助頭頸癌隨機 2 期試驗的入組。

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

接線員，我們現在準備好回答問題了。

(Operator Instructions) Jessica Fye, JPMorgan.

（操作員指示）Jessica Fye，摩根大通。

Hey, guys. Good afternoon, and thanks for taking my questions. I realize it's early days, but what can you share with us about the German PTH launch so far? And the second one is, are you seeing any external interest in your TransCon GLP-1 program? And can you remind us what the target profile you're looking to achieve is with that program? Thank you.

大家好。下午好，感謝您回答我的問題。我知道現在還為時過早，但是到目前為止，您能與我們分享有關德國 PTH 發布的哪些信息嗎？第二個問題是，您是否看到外部對您的 TransCon GLP-1 專案感興趣？您能否提醒我們您希望透過該計劃實現什麼目標？謝謝。

Thanks, Jess. Yes. As I said before, this is one week into a launch. We know that unmet medical need is there for the patients. We know how we really are providing a treatment that really are providing and minimal -- meaningful differentiation for the patient, both on short term and really also are helping in eliminating belong to risk of the disease.

謝謝，傑西。是的。正如我之前所說，距離發布已經一週了。我們知道患者的醫療需求尚未被滿足。我們知道我們如何真正提供一種治療，為患者提供最小的、有意義的差異化，無論是在短期內，還是真正有助於消除屬於該疾病的風險。

And what we observed was that exactly as what we had hoped for that position that the one of the launch make the prescription, got the material from our distributor already the first day. And in the US, you need to go to a prescription and then reimbursement and then to become to get the drug, in Germany it's different. At mid link, you get a prescription, you basically have access to be get the drop immediately at that time.

我們觀察到，正如我們所希望的那樣，發布者制定了處方，第一天就從我們的經銷商處獲得了材料。在美國，您需要先開處方，然後報銷，然後才能獲得藥物，而在德國則不同。在中間環節，你得到一個處方，你基本上可以在那時立即得到藥。

So the launch, we really look forward to provide much better update when we come to Q1, last bit of Q2, and must bear again after Q3. So we really feeling that the launch in Germany and Austria is the starting point for basic being positioned to be everywhere on the globe with these patients, and we will reach them all of the places.

因此，我們真的期待在第一季、第二季的最後一點時提供更好的更新，並且在第三季之後必須再次承受。因此，我們確實認為，在德國和奧地利的推出是基本定位於全球各地這些患者的起點，我們將涵蓋他們所有的地方。

Related to how we're using licensing of the TransCon technology outside rare disease endocrinology, yes, we have oncology without really moving forward as we only hope for and we really looking forward to '24 where we can do to improve relate to patient data how we are differentiated. You saw our differentiation in ophthalmology, we made Eyconis has been our company and we really feel that the really in an optimal value both to create value and really help the patient in this area.

與我們如何在罕見疾病內分泌學之外使用TransCon 技術許可相關，是的，我們的腫瘤學並沒有真正取得進展，因為我們只是希望，我們真的很期待24 年我們可以做些什麼來改善與患者數據的關係我們是與眾不同的。您看到了我們在眼科領域的差異化，我們使 Eyconis 成為了我們的公司，我們確實認為真正處於最佳價值，既可以創造價值，又可以真正幫助該領域的患者。

When we come to the third area that we have disclosed, we are working on, we basic half the TPL-1 class, we going for the once monthly profile and it's not only for obesity, it's also for metabolic diseases, and we feel really that we are getting the interest that the product really deserve. But it's not a product, it's a platform, a platform that can be utilized basically for the class of people wants.

當我們談到我們已經披露的第三個領域時，我們正在努力，我們將TPL-1 類的一半作為基礎，我們將每月一次的概況，它不僅針對肥胖，還針對代謝疾病，我們感覺真的我們正在獲得該產品真正應得的興趣。但它不是一個產品，它是一個平台，一個基本上可以用於人們想要的階層的平台。

Thank you.

謝謝。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

Hi, guys. Good afternoon, thanks for taking my questions. I wanted to get your updated thoughts about competition from recently approved growth hormone therapies and in particular, what is your market data telling you about (inaudible) how is that? If in any way impacting your launch. And then can you give us some data about what percent of adults currently take growth hormone replacement therapy and on average, how long does the person stay on therapy? Thanks.

嗨，大家好。下午好，感謝您回答我的問題。我想了解您對最近批准的生長激素療法競爭的最新想法，特別是您的市場數據告訴您什麼（聽不清楚）是怎麼回事？如果以任何方式影響您的發布。然後您能否給我們一些數據，說明目前接受生長激素替代療法的成年人的百分比以及平均接受治療的時間有多長？謝謝。

Thanks. That's really a pleasure to take up against the competitive landscape in the growth hormone market. And when we launched, we had a competition, the short term. It was all the different six daily growth hormone that we were competing against. We show how we will clinical different stages to this is that this standard of treatment, how we have provided a better outcome. We built the market facing to a lot to medical exception because of the product strengths, SKYTROFA. Now we see two emerging therapies coming in the long-acting spare, two product, one coming in and we don't see really impacting us because we still best in class. We have to believe that these two products have no proven second show the same outcome as a normal daily growth hormone treatment that you get in the US. So for us, the bearer for medical exception discussed improving.

謝謝。能夠應對生長激素市場的競爭格局真是一種榮幸。當我們推出時，我們進行了一場短期競爭。我們所面對的對手是每天六種不同的生長激素。我們展示了我們將如何臨床不同階段的治療標準，我們如何提供更好的結果。由於 SKYTROFA 的產品優勢，我們建立了一個面向大量醫療例外的市場。現在，我們看到兩種新興療法出現在長效備用產品中，兩種產品，一種出現，我們沒有看到真正影響我們，因為我們仍然是同類中最好的。我們必須相信，這兩種產品尚未被證明與您在美國接受的正常每日生長激素治療具有相同的結果。所以對我們來說，醫療例外的持有者討論了改進。

So for me and Ascendis, we don't see that it's really a changing anything about how we are progressing to continue and build us to a blockbuster potential just in the US, and we continue to do it because of all product strengths.

因此，對於我和 Ascendis 來說，我們認為這並沒有真正改變我們在美國繼續發展並創造出巨大潛力的方式，而且我們繼續這樣做是因為所有產品的優勢。

Related to the adult, the adult is different compared to the pediatric in many different ways. One other thing, the majority of pediatric with two because we'll have to treatment for a limit year. It could be four, five, six, seven, eight depending on the mutation of treatment. Where the adult is a chronic disease where we'll be needing a treatment for rest of your live. So I would call it a chronic disease when you're diagnosed and start the treatment. So there is a big difference related to that.

與成人相關，成人與兒童相比在許多方面都有所不同。另一件事是，大多數兒科患者都有兩個孩子，因為我們必須在有限的一年內接受治療。根據治療的突變，它可能是四個、五個、六個、七個、八個。如果成人是一種慢性疾病，我們將需要在您的餘生中進行治療。因此，當您被診斷並開始治療時，我將其稱為慢性疾病。因此，與此相關的差異很大。

We often talk about penetration degree with growth hormone treatment and what those issues different to between the pediatric and the adult is the pediatric is -- my view is penetrated our tools 60%, 70%, 80% where the adult potential is under 10% and I think is a big difference for basic your modeling how really to see and how we can develop that adult growth hormone deficiency market.

我們經常談論生長激素治療的滲透程度，以及兒科和成人之間的這些問題的不同之處在於兒科- 我的觀點是我們的工具的滲透率為60%、70%、80%，而成人潛力低於10%我認為對於基本建模來說，如何真正看到以及我們如何開發成人生長激素缺乏症市場有很大的不同。

As you said, this is our first label expansion, we will build up so we basically have access to all places where it is possible to use growth hormone because all the patients deserve to have the best product.

正如你所說，這是我們的第一次標籤擴展，我們將建立起來，這樣我們基本上就可以進入所有可以使用生長激素的地方，因為所有患者都應該擁有最好的產品。

Li Watsek, Cantor.

李·瓦塞克，康托爾。

Maybe just a follow up on TransCon PTH launch in Germany. Understanding it's early days that with what could be a good framework for us to think about the rents in that market? Any clarity you can give us around NATPARA here in patients who how quickly you may be able to onboard them? And then in terms of the patients that are enrolled in the early access program in Germany, do you have any color there as well?

也許只是 TransCon PTH 在德國推出的後續行動。了解現在還處於早期階段，什麼可以成為我們考慮該市場租金的良好框架？您能否向我們介紹一下 NATPARA 在患者中的情況，您可以多快地幫助他們？那麼對於在德國參加早期訪問計劃的患者來說，您那裡也有什麼顏色嗎？

Thanks a lot for the question. I can be bullish now and saying that all patient in Germany that have hypoparathyroidism should be on treatment because I'd say that the suite and hormone replacement therapy as everyone has had type 1 diabetes, with all of them come on treatment, likely not. But what we want to do, we are dedicated to help the patient and building up to scientific and clinical data, our dedication to develop this market to ensure as many as possible will be treated with TransCon PTH or your pumps. And it's not only in Germany and Austria, so west of Europe, this is the rest of the international market, it's basic also in the US.

非常感謝您的提問。我現在可以樂觀地說，德國所有患有副甲狀腺功能減退症的患者都應該接受治療，因為我想說，由於每個人都患有1 型糖尿病，因此套件和激素替代療法可能不會所有人都接受治療。但我們想做的是，我們致力於幫助患者並累積科學和臨床數據，我們致力於開發這個市場，以確保盡可能多的人將接受 TransCon PTH 或您的幫浦的治療。不僅在德國和奧地利，在歐洲西部，這是國際市場的其餘部分，在美國也基本如此。

So when we see this year, I think that is different element how we see the penetration will happen. We always see the benefit of position really getting the benefit seen in our own eyes that take patients -- take them on treating to fight, really to see how the product function. The benefit with TransCon PTH after the few weeks, that will receive a benefit.

因此，當我們看到今年時，我認為這是我們如何看待滲透發生的不同因素。我們總是看到位置的好處，真正獲得我們親眼所見的好處，讓患者接受治療，並真正了解產品的功能。TransCon PTH 的好處是幾週後，您將收到好處。

So then it's some kind of logical thing, how to get patients in and how to ensure that its capacity in really from the different physician size really to take the patients in. And so when we come into Q2, Q3, I think we will start to see the trend coming in and you can follow our revenue development mainly coming from where we have full reimbursement in Germany and Austria. And then you can see how we penetrate rest of Europe direct end of '24, '25 and how we pace of building up the international market in the later part of '24 and really starting to be really penetrated in a much higher level in '25 and '26.

因此，這是某種合乎邏輯的事情，如何讓患者進來，以及如何確保其能力真正從不同的醫生規模中真正接收患者。因此，當我們進入第二季、第三季時，我認為我們將開始看到趨勢，您可以追蹤我們的收入發展，主要來自我們在德國和奧地利的全額報銷。然後你可以看到我們如何在 24 世紀末和 25 年底直接滲透到歐洲其他地區，以及我們如何在 24 世紀後期建立國際市場，並在 2015 年真正開始在更高水平上進行滲透。25 和 26。

David Lebowitz, Citi.

大衛‧勒博維茨，花旗銀行。

Thank you for taking my question. Given the emergence of GLP-1s and their effect on lean muscle mass, is there a potential role for growth hormone due to the success of the GLP-1s?

感謝您回答我的問題。鑑於 GLP-1 的出現及其對瘦肌肉質量的影響，生長激素是否會因 GLP-1 的成功而發揮潛在作用？

This question, that basic are going back to the mode of action and the benefit you'll see with GLP-1. I personally was a little bit skeptical about the entire GLP-1 class in obesity, but it's too because I'm pretty conservative in many ways. But what I'm 100% sure now is going to be a huge fuse clubs. And we see that benefit coming out really on a lot of different treatment aspect, it's not only just losing weight, there's a lot of other treating benefit to this class.

這個問題的基本內容是回到 GLP-1 的作用模式和好處。我個人對整個 GLP-1 類肥胖症有點懷疑，但這也是因為我在很多方面都相當保守。但我現在 100% 確定這將是一個巨大的保險絲俱樂部。我們看到這種益處確實體現在許多不同的治療方面，它不僅僅是減肥，而且此類藥物還有很多其他治療益處。

The negative part is that is new basic either in a position that you losing a large amount of muscle mass and specific, if you're not here to the treatment and make period of brake start I'll begin, period of break, you can basically be in a position than when you're not treating, you build up the fat tissue faster than the massive weight. And I think is a really interesting perspective at basic could see growth hormone treatment because that is really where the benefit of growth hormone is that it can build up the muscle mass in a much more stronger mass in a very normalized manner.

負面的部分是，這是新的基礎，無論是在您失去大量肌肉質量的情況下，還是具體而言，如果您不在這裡接受治療並進行製動期開始，我將開始，休息期，您可以基本上，與不治療時相比，脂肪組織的形成速度比體重增加的速度更快。我認為，從根本上來說，生長激素治療是一個非常有趣的觀點，因為這確實是生長激素的好處在於，它可以以非常正常的方式以更強大的質量增強肌肉質量。

And I think you are right, and I would like to explore that possibility.

我認為你是對的，我想探索這種可能性。

Thanks for taking my question.

感謝您提出我的問題。

Joseph Schwartz, Leerink Partners.

約瑟夫‧施瓦茨，Leerink Partners。

Hi there. Thanks very much. I was wondering if you could talk about the work you did to arrive at your estimate that 70,000 adults have product hypoparathyroidism in Germany and who are the 20,000 patients that you're targeting there, and how is the target population of United States compare to the total of hypopara population of the US where we have some guidelines. Just wondering if that influences the proportion of the market that you think is most addressable here in the United States. Thanks.

你好呀。非常感謝。我想知道您是否可以談談您所做的工作，以得出德國有70,000 名成年人患有副甲狀腺功能減退症的估計，以及您所針對的20,000 名患者是誰，以及美國的目標人群與我們有一些指導方針的美國低下肢人口總數。只是想知道這是否會影響您認為在美國最適合的市場比例。謝謝。

I think you've got all the questions and when we compare the demographic between Germany and US, it consists of the basic two group the post-surgical with a one group, and then you can see the more hemological genetic idiopathic background where you typical will see a rise much earlier in stage of life. Germany potential is a little bit unique with the last number of patient because -- and I think it potentially is built on the high level of intensive head and neck operation because of strong folks of diagnosis. And from that perspective is, yes, there is potentially more post-surgical patients in Germany that you see in the US. For example, if you take a country like France, France must more relate to what you will see of treatment way that you see in the US.

我想你已經有了所有的問題，當我們比較德國和美國之間的人口統計時，它由基本的兩組和一組術後組成，然後你可以看到更多的血液學遺傳特發性背景，你典型的會在生命階段更早看到上升。德國的潛力在最後一批病人身上有點獨特，因為——我認為它可能建立在高水平的密集頭頸手術的基礎上，因為人們的診斷能力很強。從這個角度來看，是的，德國的術後患者可能比美國更多。例如，如果您選擇像法國這樣的國家，那麼法國必須與您在美國看到的治療方式更加相關。

So when we see this different patient population, all of them will benefit of that TransCon PTH treatment of Europe. It's not like one group of loyal one call this beneficial in the treatment on it. So all of them to serve to have a life for TransCon PTH.

因此，當我們看到這些不同的患者群體時，他們所有人都將受益於歐洲的 TransCon PTH 治療。這並不像一群忠誠的人認為這對治療有益。所以他們所有人都為了 TransCon PTH 的生命而服務。

Going back to what you say when we talk about the 22,000 patients and it's not because we see subpopulation that see more benefit all this benefit from that. When we talk about what 22,000 patients which we tried to address first, is the patient that from a pharmaco economic perspective, have a hot type on the society that can be potentially come to the state of impairment, that can come to a state of visit hospitalization a lot, there will come to a state where they cannot function because of cut-and-sew effect that cannot get the normal life. So outcome to that perspective is not really a treatment benefit, this is more that for this society, and this is where we always need to be. We need to benefit the patient, the society, and everyone as all stakeholders. And this is the burden for society as much higher for these 22,000 patients.

回到你所說的，當我們談論 22,000 名患者時，這並不是因為我們看到亞人群從中受益更多。當我們談論我們首先試圖解決的 22,000 名患者時，從藥物經濟學的角度來看，這些患者是社會上的熱門類型，可能會進入受損狀態，可能會進入就診狀態住院次數多了，就會因為裁剪效應而達到無法發揮功能的狀態，無法獲得正常的生活。因此，這種觀點的結果並不是真正的治療益處，這更多的是為了這個社會，而這正是我們始終需要的。我們要造福病人、造福社會、造福每個利害關係人。對於這22,000名患者來說，這對社會來說是一個更大的負擔。

Very helpful. Thank you.

很有幫助。謝謝。

Derek Archila, Wells Fargo.

德里克·阿奇拉，富國銀行。

Hey, good afternoon, and thanks for taking the questions. Just two from us. I just wanted to clarify if SKYTROFA a $1 billion product in the US just pediatrics alone, or does that assume contribution from adult GHD as well? And then just in terms of the cost structure of the endo business, is this $600 million cost base now? How should we be thinking about it for the future. And just how -- your thoughts about profitability of that business? Thanks.

嘿，下午好，感謝您提出問題。離我們只有兩個人。我只是想澄清一下，SKYTROFA 在美國價值 10 億美元的產品是否只是兒科產品，還是也假設成人 GHD 的貢獻？那麼就內切業務的成本結構而言，現在這 6 億美元的成本基礎是嗎？未來我們該如何思考。您對該業務的獲利能力有何看法？謝謝。

I will take the first question and then Scott is really happy today now because he actually has an opportunity to come to some of the financial numbers is running so dedicated over time.

我將回答第一個問題，然後斯科特今天真的很高興，因為他實際上有機會了解一些隨著時間的推移而如此專注的財務數據。

When we look on the potential market, yes, you can see we will have adult growth hormone deficiency. We will pursue some of the other indication too. But we also need to say that we are liberating and normal somatropin molecule, which are well-known entity for all the different indication that seen the benefit on growth hormone. And if you go to the market of the daily growth hormone and see what is the dynamic there, the dynamic is that none of the daily growth hormones basic because we are somatropin too, all of them, basic idea in a position. None of them have all the indications where after being reimbursed are used to date because none have really take the effort to go through all the different indication. So it could be potential for the same thing will be applied also on the long-acting products that are providing the same somatropin molecule.

當我們觀察潛在市場時，是的，您可以看到我們將出現成人生長激素缺乏症。我們還將研究其他一些跡象。但我們還需要說的是，我們正在釋放正常的生長激素分子，這是眾所周知的實體，因為所有不同的跡像都顯示出對生長激素的益處。如果你去每日生長激素市場，看看那裡的動態是什麼，動態是，沒有一種每日生長激素是基本的，因為我們也是生長激素，所有這些都處於一個位置的基本想法。他們中沒有一個擁有在報銷後迄今為止使用的所有適應症，因為沒有人真正花精力去檢查所有不同的適應症。因此，同樣的事情也有可能適用於提供相同生長激素分子的長效產品。

Scott, will you talk a little bit about expenses and numbers? In less than 10 minutes?

史考特，你能談談開支和數字嗎？不到10分鐘？

How much time do we have? Thanks, Derek. It's good to have a finance question. So, as you saw here in the Q4, realizing now the benefits of the streamlined operation, operational changes in processes that Jan has talked about, with OpEx going down to about [155] total. And then of course, next year, you'll see more come off as a result of basically no P&L burden from ophthalmology.

我們還有多少時間？謝謝，德里克。有一個財務問題很好。因此，正如您在第四季度看到的那樣，現在意識到 Jan 談到的簡化營運和流程營運變化的好處，營運支出總計下降到約 [155]。當然，明年，你會看到更多的脫落，因為眼科基本上沒有損益負擔。

You should look at this as a product of the way that we've developed our portfolio and how efficient it can be. I think if you look at our cost for TransCon Growth Hormone and realize the stage of that product, how mature it is, the cost should be dropping pretty substantially in the coming years. And overall, we're going to be pretty efficient in R&D. So I would expect more shift from 60, 40 R&D, SG&A in '23 to maybe 50, 50 or so in '24.

您應該將其視為我們開發產品組合的方式及其效率的產物。我認為，如果你看看我們 TransCon 生長激素的成本並意識到該產品的階段、它的成熟程度，那麼未來幾年成本應該會大幅下降。總的來說，我們的研發將會非常有效率。因此，我預計會有更多的轉變，從 23 年的 60、40 個研發、SG&A 到 24 年的 50、50 個左右。

Longer run, we'll be efficient in R&D, and as we expand globally, I would expect some increase in SG&A as we add people in 30, 40, 50 countries, but it should be pretty minimal. And as you saw going from Q3 to Q4, our SG&A was basically flat even if we launched an additional product and got ready to launch a second product in Germany.

從長遠來看，我們將在研發方面保持高效，並且隨著我們在全球範圍內擴張，我預計隨著我們在30、40、50 個國家/地區增加人員，SG&A 會有所增加，但這應該是相當小的。正如您所看到的，從第三季度到第四季度，即使我們推出了額外的產品並準備在德國推出第二個產品，我們的銷售及管理費用也基本持平。

Thank you.

謝謝。

One comment, what you see the result of something was basic element that happening in '23. You don't suddenly change the company. You don't some this streamline the company. It takes a lot of effort. It took us -- started beginning of '23, we'll find out how can we build a leaner Ascendis, more productive, really focus on optimizing processes, administration, and everything like that. And we worked very successful to that. It was a hard task, not already always pleasant, but we're there now. We are where we want to be now. We are still optimizing our processes because we scaling for potential having 5,000 to have 50,000 processes and you cannot use the same PV system that you used to 5,000 to 50,000.

一則評論是，你所看到的某件事的結果是 23 年發生的基本要素。你不會突然改變公司。你不應該精簡公司。這需要付出很大的努力。我們從 23 年初開始，我們將找出如何建立一個更精簡、更有效率的 Ascendis，真正專注於優化流程、管理以及類似的一切。我們在這方面做得非常成功。這是一項艱鉅的任務，並不總是令人愉快，但我們現在做到了。我們現在就在我們想要的地方。我們仍在優化我們的流程，因為我們將潛在的 5,000 個流程擴展到 50,000 個流程，並且您無法使用過去 5,000 到 50,000 個流程的相同光伏系統。

So this is why we really are still optimizing processes, changing the company, because we cannot be a leading biopharma company at the same way we operated a large biotech company where we basically focus on clinical development and future commercialization. So we are still transforming. We still changing our processes, and that is what we need to continue to be truly competitive to in this landscape.

因此，這就是為什麼我們仍在優化流程、改變公司，因為我們無法像經營一家大型生物技術公司那樣成為一家領先的生物製藥公司，而我們基本上專注於臨床開發和未來的商業化。所以我們還在轉型。我們仍在改變我們的流程，這就是我們在這一領域繼續保持真正競爭力所需要的。

Kelly Shi, Jefferies.

施凱莉，傑弗里斯。

Thank you for taking my questions. Maybe I'll switch topics or two to address certain key. You have talked about the improvement on our muscle function and other companies still talk about a mile of proportionality, upper to lower body ratio. Just curious, have you also have that kind of proportionality as well? And also, why it comes to the combination with SKYTROFA, what would be the most differentiated clinical benefit compared to TransCon CNP alone? Thank you.

感謝您回答我的問題。也許我會切換一兩個主題來解決某些關鍵問題。你談到了我們肌肉功能的改善，而其他公司仍在談論一英里的比例，上半身與下半身的比例。只是好奇，你也有這樣的比例嗎？另外，為什麼要與 SKYTROFA 合併使用，與單獨使用 TransCon CNP 相比，最有差異化的臨床效益是什麼？謝謝。

Thanks. I will start from the back because if you have (inaudible) born with achondroplasia being started treatment as a newborn, our belief is that good basic with nearly have normal growth in this period of time where you have growth related to linear growth. You were not really address and stop or can't stop to address the co-morbidities because that will exist the rest of the life. And this is when we see on the integrated aspect of achondroplasia, we see the linear growth as one part of the disease. And we see the other impact of the hyperactive pathway have on other aspect, like for example, muscle weakness and other aspect, which are really from a mode of action, is different from compare to what you see on the content place that really a limit in the ways that get linear growth.

謝謝。我將從後面開始，因為如果您（聽不清楚）出生時患有軟骨發育不全，並在新生兒時開始接受治療，我們相信，在這段時間內，您的生長基本上與線性生長相關，幾乎具有正常生長。你沒有真正解決並停止或無法停下來解決共病，因為這將在餘生中存在。當我們看到軟骨發育不全的綜合方面時，我們將線性生長視為疾病的一部分。我們看到過度活躍途徑對其他方面的其他影響，例如肌肉無力和其他方面，它們實際上來自一種作用模式，與您在真正限制的內容中看到的不同。以線性增長的方式。

So when we think about how we are positioning our combination trial is that what everyone else have seen of data for the impressive amount of clinical data that's come out from BioMarin we needed to facilitate, all of that showing that your normalized growth for that waste majority of the patients.

因此，當我們考慮如何定位我們的組合試驗時，其他人都看到了我們需要促進的來自 BioMarin 的大量臨床數據，所有這些都表明，大多數廢物的正常化增長患者的。

But if you have a child that got born and first started treatment of eight years, they still have a lack of growth. So when we saw all the data that's been generated by daily growth hormone, more than 30, 40 population, really intensive trials with 40, 50 children. And we see that basically can induce catch-up growth as you can do in growth hormone deficiency because that is what we do in growth hormone deficiency.

但如果你的孩子出生並開始治療八年，他們仍然缺乏生長。因此，當我們看到所有每日生長激素產生的數據時，對 30、40 多個人群、40、50 名兒童進行了真正的密集試驗。我們發現這基本上可以誘導追趕性生長，就像在生長激素缺乏症中所做的那樣，因為這就是我們在生長激素缺乏症中所做的。

The mode of growth hormone is that you can reset the growth to be normal as a final height. If you are fine and good to hear the treatment. But you could only do that in order growth hormone deficiency, if you have a catch-up growth. Meaning that you grow more in the first two, three years than your basics, we'll see of a normal growth.

生長激素的作用方式是可以將生長重置為正常的最終身高。如果您身體狀況良好並且願意聽到治療。但如果你有追趕性生長，你只能在生長激素缺乏的情況下這樣做。這意味著你在前兩三年的成長比你的基礎還要多，我們會看到正常的成長。

That is why when you think about the child with growth hormone deficiency not had been treated for eight, nine years, starting potential treatments and then suddenly hit the parents height as expected. This is because of (inaudible) growth. And you'll see the same thing in achondroplasia. If you start to give them a growth hormone, I see growth to pick up to seven, eight centimeters, not as robust as you see in growth hormone deficiency and is likely because they still have a block down on the contemplate because they also need CMP.

這就是為什麼當你想到患有生長激素缺乏症的孩子八、九年沒有接受治療，開始潛在的治療，然後突然達到父母預期的身高。這是因為（聽不清楚）成長。你會在軟骨發育不全中看到同樣的情況。如果你開始給他們注射生長激素，我發現他們的生長會增加到七、八厘米，但不像生長激素缺乏時那麼強勁，很可能是因為他們仍然有阻礙，因為他們也需要 CMP 。

So when we think about the perspective of combination trials, this is the children that are not treated. And this is basic element, majority of children today that is not going treated either from the newborn and really need some catch up growth really to get a boost in the growth. And this is why we are running describe, my expectation and now I can be trying to do some things as it's very dangerous. But I believe you can potentially grow them up to eight, nine centimeters just by combination treatment, because you get the catch up growth for the first one, two years.

因此，當我們從聯合試驗的角度考慮時，這些孩子並沒有得到治療。這是基本要素，當今大多數兒童從新生兒起就沒有接受治療，確實需要一些追趕生長才能促進生長。這就是為什麼我們正在運行描述，我的期望，現在我可以嘗試做一些事情，因為這是非常危險的。但我相信，透過聯合治療，你有可能將它們長到八、九釐米，因為你可以在第一年、兩年內實現追趕生長。

And this is the rational really for us to go out and make that treatment regime because we do the same as most of what we normalize growth. So proportionality, yes, we see the same positive trend in proportionality that we have seen and expected to see. And we will see more and more when we see more data from longer part of treatment because it takes longer time to see the right benefit on this or change of disproportionality. But we definitely are seeing the same positive development.

這才是我們走出去製定治療方案的真正合理性，因為我們所做的與我們實現成長正常化的大部分措施相同。所以，比例，是的，我們看到了我們已經看到和預期看到的比例的正面趨勢。當我們從治療的較長部分中看到更多數據時，我們會看到越來越多的數據，因為需要更長的時間才能看到這方面的正確益處或不成比例的變化。但我們確實看到了同樣的積極發展。

Thank you.

謝謝。

Paul Choi, Goldman Sachs.

保羅‧崔，高盛。

Hi, good afternoon, and thanks for taking our questions. I also want to ask on TransCon CNP for the -- your Phase 3 ApproaCH study. Can you maybe just share what metrics or details you'll provide with the top-line results and what is your medical conference presentation plans for that data. And then second, on the regulatory strategy, can you maybe just help us understand the urgency to file the NDA in the same quarter Just kind of what the reasoning behind that is or you're just potential concerned about a full approval for BioMarin's VOXZOGO? Just maybe some color there would be helpful. Thank you very much.

你好，下午好，感謝您回答我們的問題。我也想向 TransCon CNP 詢問你們的第三階段 ApproaCH 研究。您能否分享一下您將提供哪些重要結果的指標或詳細信息，以及您對該數據的醫學會議演示計劃是什麼？其次，關於監管策略，您能否幫助我們了解在同一季度提交 NDA 的緊迫性？這背後的原因是什麼，或者您只是可能擔心 BioMarin 的 VOXZOGO 獲得完全批准？也許一些顏色會有幫助。非常感謝。

That's pretty simple about this filing. Ascendis approach is to do it as fast as possible in the highest quality and see if anyone else is working the company and not living up to this aspect, they should leave. So if I can get someone to do the filling in the same quarter we get the data, we should do it. When we come to the Phase 3 data, yes, we have a primary endpoint because that got is that this asset traditional ways of a primary endpoint is that really up and rational in point for achondroplasia. I have my doubt, I think is more surrogate marker, annualized height velocity. A treatment is to change the co-morbidity of the disease.

這份文件的內容非常簡單。Ascendis 的方法是以最高的品質盡可能快地完成，看看是否有其他人在公司工作並且沒有達到這方面的要求，他們應該離開。因此，如果我能讓人在我們獲得數據的同一季度進行填寫，我們就應該這樣做。當我們看到第三階段數據時，是的，我們有一個主要終點，因為這項資產傳統的主要終點方式對於軟骨發育不全來說確實是合理的。我有我的疑問，我認為更多的是替代指標，年化身高速度。治療是為了改變疾病的共病。

So the primary endpoint for me is like a surrogate mother as truncal fat is for adult growth hormone deficiency. That is not really the key treatment objective in adult growth hormone deficiency. You'll see other aspect of the treatment that's more important. But this has established in point.

因此，對我來說，主要終點就像代孕母親一樣，因為軀幹脂肪是針對成人生長激素缺乏症的。這並不是成人生長激素缺乏症的真正關鍵治療目標。您會看到治療的其他方面更重要。但這已經成立了。

So when we go to the secondary endpoint, and I said is very simple in my sixth, we're going in and look on the effect on co-morbidities, and we do it on a lot of different angles. And we want to be sure that we currently have the best possible way. And the best possible way we can do it is to look on the comorbidities basic that is developed into what we can measure in different physical function, daily function. We do a lot of radio liability because we know the texture of the child need to be perfect so we hundred percent sure we had developed different health related outcome measuring. And I believe that taking all these aspect into it, we will find benefit that no one had been seeing and I hope it will both come for quality of life, body composition, physical function, and also the logical endpoint that basic providing different way of how they improve the texture.

因此，當我們到達次要終點時，我在第六個終點中說非常簡單，我們將研究對合併症的影響，我們從許多不同的角度進行研究。我們希望確保我們目前擁有最好的方法。我們能做到這一點的最好方法是觀察基本的合併症，將其發展為我們可以在不同的身體功能、日常功能中測量的內容。我們做了很多無線電責任，因為我們知道孩子的質地需要完美，所以我們百分之百確定我們已經開發了不同的健康相關結果測量。我相信，考慮到所有這些方面，我們會發現沒有人看到過的好處，我希望它既能提高生活品質、身體組成、身體功能，也能實現基本提供不同方式的邏輯終點他們如何改善質地。

And that medical meeting up (technical difficulty)

還有那次醫療會議（技術難度）

I think the (inaudible) are not driven by a medical meetings. So there are some people are saying that in the data out because of medical meeting, I think when you have mature data used to come out it so everyone can see that data. We are not waiting with disclosing data just because of medical meetings.

我認為（聽不清楚）不是由醫學會議推動的。所以有人說，在醫學會議上公佈的數據中，我認為當你有成熟的數據時，就會出來，這樣每個人都可以看到這些數據。我們不會僅僅因為醫學會議而等待披露數據。

Andreas Argyrides, Wedbush.

安德烈亞斯·阿吉里德斯，韋德布希。

Congrats on the progress, and thanks for taking our questions. Just a couple here from us. When you think about CNP, can you give us a little bit of your thoughts around the rationale to extend into adults with high-profile with achondroplasia instead of going to help achondroplasia like the other companies space and then looking at VOXZOGO and the growth that they've seen primarily driven by ex US, maybe you can give us a sense of why it's offer off to a slower start in the US? Is driven by the fact that they have been focusing on height versus other quality of life measures? And then just one last one on the oncology programs. If you don't find a partner to bring these programs, would you consider spinning them off likely there will be up margin programs? Thanks.

恭喜您的進展，並感謝您提出我們的問題。我們這裡只有一對夫婦。當您想到CNP 時，您能否給我們一些您的想法，談談您將業務擴展到患有軟骨發育不全的成年人的基本原理，而不是像其他公司那樣幫助軟骨發育不全，然後看看VOXZOGO及其成長情況已經看到主要由前美國推動，也許您可以讓我們了解為什麼它在美國的起步較慢？是因為他們一直關注身高而不是其他生活品質衡量標準嗎？然後是關於腫瘤學計畫的最後一項。如果你找不到合作夥伴來實施這些計劃，你會考慮將它們分拆出來嗎？可能會有提高利潤的計劃？謝謝。

Okay. Let me start on the last one because it's very easy. We are here to do the optimal for the patient to get our product being penetrated to as many as possible patients. And we believe that we are in a position when we have seen all the data that will come out, end of this year, we already have seen the interest in our programs now. We feel pretty confident they will do the optimal where we see the fastest best way to come out to the patient and we create most value for Ascendis' shareholders. That will be the driver from our decision.

好的。讓我從最後一個開始，因為它很簡單。我們致力於為患者提供最佳的服務，讓我們的產品滲透到盡可能多的患者手中。我們相信，當我們看到今年年底將公佈的所有數據時，我們已經看到了人們對我們的計劃的興趣。我們非常有信心他們會採取最佳措施，以最快的最佳方式向患者提供信息，並為 Ascendis 股東創造最大價值。這將是我們做出決定的驅動力。

Then you had to comments to CNP? The first one was --

那麼你必須向CNP發表評論嗎？第一個是--

Why not hypochondroplasia?

為什麼不是軟骨發育不全？

Why not hypochondroplasia? That is pretty good, interesting perspective for hospitals. That is something we are discussing a lot because hypochondroplasia is a (inaudible) for achondroplasia. And I think we will not move over to a hypochondroplasia. Before we really have provided the optimal treatment, the best treatment that really addressing co-morbidity in achondroplasia, why jump over to something where you basically have not provided a treatment option, but potentially only providing some few linear growth and the linear growth, you could get that for the last 20 years, just by giving daily growth hormone.

為什麼不是軟骨發育不全？對醫院來說，這是一個非常好的、有趣的觀點。這是我們常討論的問題，因為軟骨發育不全是軟骨發育不全的一種（聽不清楚）。我認為我們不會發展為軟骨發育不全。在我們真正提供最佳治療，真正解決軟骨發育不全合併症的最佳治療之前，為什麼要跳到基本上沒有提供治療​​選擇，但可能只提供一些線性生長和線性生長的地方，你在過去的20年裡，只需每天注射生長激素就可以實現這一目標。

So I don't see that is really a treatment benefit, that is just providing linear growth. What we're trying to address is basically the co-morbidity of the disease and we will continue to do that until we are find best possible solution to give them a meaningful improvement in quality of life.

所以我認為這並不是真正的治療益處，這只是提供線性成長。我們試圖解決的基本上是疾病的共病問題，我們將繼續這樣做，直到找到最佳解決方案，使他們的生活品質得到有意義的改善。

And the other thing is that I think these two things related to each other. I don't believe being short is a disease, even if I'm pretty tall. So I actually don't believe being short is a disease. And I'd like to think you should never consider short to be a disease. I believe that taking just a linear growth, is more appealing in some countries than others, and definitely in US, it's not a disease to be short.

另一件事是我認為這兩件事是相互關聯的。我不認為矮是一種病，即使我很高。所以我其實不認為矮是一種病。我認為你永遠不應該將身材矮小視為一種疾病。我相信，在某些國家，採取線性成長比其他國家更有吸引力，尤其是在美國，做空並不是一種疾病。

Yaron Werber, TD Cowen.

亞龍·韋伯，TD·考恩。

This is Joyce for Yaron, thanks for taking our question. Just maybe help me get your thoughts on the emerging competitive landscape for hypopara. You clearly had to market, but there's another one staring to (inaudible) analog in Phase 3, and then there are a couple of other than a pipeline behind that. Some, looking to develop oral candidates or once weekly candidates. So just any thoughts or comments there would be great. Thank you.

我是亞龍的喬伊斯，感謝您提出我們的問題。也許可以幫助我了解您對低產婦新興競爭格局的看法。顯然，你必須進行行銷，但在第三階段還有另一個正在關注（聽不清楚）模擬的產品，然後除了管道之外還有其他一些產品。有些人希望培養口頭候選人或每週一次的候選人。所以任何想法或評論都會很棒。謝謝。

Thanks a lot. When I took a look from a endocrinology perspective and look under a logical system in the body, the complexity of that has really to provide and treatment of and hormone replacement therapy in a situation where the biology has been extremely multiple organs effect, having the right close, not too hypo and see what we did in SKYTROFA, we provided with somatropin the same molecule that really are being produced by the (inaudible) gland, and I believe when also go to hypopara, this patient need to have a physiological level of PTH then providing the same mode of action.

多謝。當我從內分泌學的角度看身體的邏輯系統時，它的複雜性確實需要在生物學受到多器官影響的情況下提供治療和激素替代療法，具有正確的方法接近，不要太低，看看我們在SKYTROFA 中所做的，我們提供了與（聽不清楚）腺體真正產生的相同分子的生長激素，我相信當也去低處時，該患者需要有一個生理水平PTH則提供相同的作用方式。

I actually went to a conference and heard some of the question for precision on some of the other competitive products. And one of the key question that came up, we know PTH have effect on so many different organs. When you change the entire mode of action, how can you really prove and believe you can create the same normal physiological system that you will expect to get with a normal enormous PTH.

事實上，我參加了一次會議，聽到了一些關於其他一些競爭產品的精確度的問題。出現的關鍵問題之一是，我們知道 PTH 對許多不同的器官有影響。當您改變整個作用模式時，您如何才能真正證明並相信您可以創建與正常巨大 PTH 所期望的相同的正常生理系統。

How we defined TransCon PTH to provide a normal, same as inductors PTH with the exactly the same path that give the mode of action in the physiological levels. And I don't think any treatment that changing that will provide the same holistic benefit on all aspects of hypopara for any patient.

我們如何定義 TransCon PTH 以提供與電感器 PTH 相同的正常路徑，並具有完全相同的路徑，從而給出生理水平的作用模式。我認為任何改變這一點的治療方法都不會為任何患者的下肢下垂的各個方面提供相同的整體益處。

Thank you.

謝謝。

Leland Gershell, Oppenheimer.

利蘭·格謝爾，奧本海默。

Thanks for taking our questions. Two from us, one each on SKYTROFA and TransCon PTH. On SKYTROFA, again, you mentioned in past commentary about the decreasing investment among the daily growth hormone companies and products onto just here, any updated color you may be able to share with respect to the marketplace in terms of the dailies, if that's a continuing trend that you're seeing. With respect to and TransCon PTH, as we anticipate approval and launch from Q3 of this year, if you could remind us the number of patients you have available in the States between both from those made in the open label studies as well as those who are in the EAP. Thank you.

感謝您回答我們的問題。我們提供兩份，SKYTROFA 和 TransCon PTH 各一份。在 SKYTROFA 上，您在過去的評論中再次提到了每日生長激素公司和產品之間的投資減少，就在這裡，您可以分享關於每日市場的任何更新的顏色，如果這是一個持續的您所看到的趨勢。關於 TransCon PTH，我們預計將於今年第三季度獲得批准並推出，請您提醒我們，您在美國擁有的患者數量，包括開放標籤研究中進行的患者以及正在接受治療的患者數量。在 EAP 中。謝謝。

Yes, you're right. We have discussed a lot of what we call the long term or than many years' perspective of the consolidation in the growth hormone market. And the trend is happening exactly as expected. Specific with the interns of the two other long-acting, the basic with daily growth hormone is starting to disappear more and more because this two company that's providing them the key element where we have seen them taking market is basic taking the own product, their own product on the daily growth hormone class and then transform them over to the long-acting where we take it from everywhere because of improve treatment outcome.

你是對的。我們已經討論了很多我們所說的生長激素市場整合的長期或多年的觀點。而這趨勢的發生完全符合預期。具體到另外兩家長效藥物的實習生，每日生長激素的基本成分開始越來越消失，因為這兩家公司為他們提供了我們看到他們佔領市場的關鍵要素，即基本上採用自己的產品，他們的產品我們將自己的產品用於日常生長激素類，然後將其轉變為長效產品，我們從各地獲取它，以改善治療效果。

So I see our market share being basic the same as we some way predicted from three, four years. What is happening is that the two all and long acting just take part of the daily growth hormone, we never thought we'd exit will basic having access to. And so our market penetration, our market share or market value of SKYTROFA is basic unaffected to what we have seen.

因此，我認為我們的市佔率與我們對三、四年的預測基本上相同。正在發生的事情是，這兩種全效和長效只是日常生長激素的一部分，我們從未想過我們基本上會能夠使用。因此，我們的市場滲透率、市場佔有率或 SKYTROFA 的市場價值基本上沒有受到我們所看到的影響。

Go to TransCon PTH and the US specific. The question you are providing me is the team because our both Phase 2 and Phase 3 would have really high retention and continue to have extremely high retention now on fourth or fifth year, I cannot remember now more. The problem is that I cannot really remember how many patient that is in Europe or US between the different trials. So therefore, in my numbers is really bit weak in that, I would think is about 40, 60 or something like that, but I'm not 100% sure about that. So please, Scott can give you a number when he's finished here and send it to you.

轉到 TransCon PTH 和美國具體資訊。你提供我的問題是團隊，因為我們的第二階段和第三階段都會有非常高的保留率，並且在第四年或第五年繼續保持極高的保留率，我現在記不清了。問題是我真的記不清不同試驗之間有多少歐洲或美國患者。因此，我的數字確實有點弱，我認為大約是 40、60 或類似的數字，但我對此並不能 100% 確定。所以請斯科特完成這裡後給您一個號碼並發送給您。

Great. Thank you very much.

偉大的。非常感謝。

Thank you. That's all the time we have for the Q&A today. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.

謝謝。這就是我們今天問答的全部時間。感謝您參加今天的會議。這確實結束了該程式。您現在可以斷開連線。大家，祝你有美好的一天。

Have a great day.

祝你有美好的一天。