諾和諾德 (NVO) 2021 Q1 法說會逐字稿

Hello, and welcome to the Q1 2021 Novo Nordisk A/S earnings conference call. (Operator Instructions) Today, I'm pleased to present Lars Fruergaard Jørgensen. Please go ahead with your meeting.

您好，歡迎參加諾和諾德公司 2021 年第一季度財報電話會議。（操作員說明）今天，我很高興向您介紹 Lars Fruergaard Jørgensen。請繼續您的會議。

Thank you very much, and welcome to this Novo Nordisk Earnings Call for the first 3 months of 2021 and outlook for the year. I'm Lars Fruergaard Jørgensen, the CEO of Novo Nordisk. With me I have our Chief Financial Officer, Karsten Munk Knudsen; and Executive Vice President and Head of Development, Martin Holtz Lange. Also present and available for Q&A session is Executive Vice President and Head of Commercial Strategy and Corporate Affairs, Camilla Sylvest.

非常感謝，歡迎參加諾和諾德 2021 年前 3 個月的收益電話會議以及今年的展望。我是諾和諾德公司首席執行官拉爾斯·弗魯爾加德·約根森 (Lars Fruergaard Jørgensen)。和我一起的還有我們的首席財務官 Karsten Munk Knudsen；執行副總裁兼開發主管 Martin Holtz Lange。出席並參加問答環節的還有執行副總裁兼商業戰略和公司事務主管卡米拉·西爾維斯特 (Camilla Sylvest)。

Today's earnings release and the slides for this call are available on our website, novonordisk.com. Please note that this call is being webcasted live and this call -- and the recording will be made available on Novo Nordisk's website. The call is scheduled to last 1 hour. The presentation is structured as outlined on slide 2. Please note, all sales and operating profit growth statements will be at constant exchange rates unless otherwise specified. The Q&A session will begin in about 25 minutes.

今天的收益發布和本次電話會議的幻燈片可在我們的網站 novonordisk.com 上查看。請注意，本次電話會議正在進行網絡直播，並且錄音將在諾和諾德的網站上發布。通話預計持續 1 小時。該演示文稿的結構如幻燈片 2 所示。請注意，除非另有說明，所有銷售和營業利潤增長報表均採用固定匯率。問答環節將在大約 25 分鐘後開始。

Please turn to slide 3. As always, I need to advise you that this call will contain forward-looking statements. Such forward-looking statements are subject to risk and uncertainty that could cause actual results to differ materially from expectations. For further information on the risk factors, including the uncertainties related to COVID-19, please see the company announcement for the first 3 months of 2021 and the slide prepared for this presentation.

請翻到幻燈片 3。與往常一樣，我需要通知您，本次電話會議將包含前瞻性陳述。此類前瞻性陳述存在風險和不確定性，可能導致實際結果與預期存在重大差異。有關風險因素的更多信息，包括與 COVID-19 相關的不確定性，請參閱公司 2021 年前 3 個月的公告以及為本次演示準備的幻燈片。

Please turn to the next slide. In the past 3 months, Novo Nordisk has progressed on all 4 dimensions of our strategic aspirations. We want to continue to add value to societies while we are taking steps on prevention and access. We have announced 2 partnerships where we invest in healthier urban populations as well as support frontline health care workers in low and middle-income countries to improve access to diabetes care. As part of our Circular for Zero environmental strategy, we are pleased to note that several suppliers have already committed to the zero carbon emission target by 2030 when supplying Novo Nordisk. This is expected to eliminate an estimated 15% of Novo Nordisk supplier carbon emissions.

請翻到下一張幻燈片。在過去的三個月裡，諾和諾德在我們戰略願景的所有四個方面都取得了進展。我們希望在採取預防和獲取措施的同時繼續為社會增加價值。我們宣布了兩項合作夥伴關係，投資於更健康的城市人口，並支持低收入和中等收入國家的一線醫護人員，以改善獲得糖尿病護理的機會。作為我們“零碳排放通告”環境戰略的一部分，我們很高興地註意到，多家供應商在向諾和諾德供貨時已承諾到 2030 年實現零碳排放目標。預計這將消除諾和諾德供應商約 15% 的碳排放。

Martin will come back to key milestones within innovation but firstly, I want to mention that while we had an initial setback for Ozempic 2.0 milligram in the U.S. with the FDA issued refusal to file letter, we are working towards a resubmission in the second quarter. Furthermore, I'm happy to share with you that Ozempic has been approved for type 2 diabetes treatment and established cardiovascular disease in China. For commercial execution, we have progressed on all 3 strategic aspirations.

馬丁將回到創新的關鍵里程碑，但首先，我想提一下，雖然我們在美國的 Ozempic 2.0 毫克產品最初遇到了挫折，因為 FDA 拒絕提交信件，但我們正在努力在第二季度重新提交。此外，我很高興與您分享，Ozempic已在中國獲批用於治療2型糖尿病和心血管疾病。在商業執行方面，我們在所有 3 個戰略願景上都取得了進展。

Lastly, within financials, despite a tough comparator, which has been partly offset by inventory changes and timing of shipments in the first quarter of [2029], sales grew by 7%, while operating profit increased by 3%, both measured at constant exchange rates.

最後，在財務方面，儘管進行了嚴格的比較，但[2029]第一季度的庫存變化和發貨時間部分抵消了這一影響，但銷售額增長了7%，營業利潤增長了3%，兩者均按恆定匯率計算費率。

Please turn to slide 5. The sales increase of 7% was driven by 9% sales growth in international operations and North America operations growing by 5%. The negative impact for COVID-19 related stocking in the first quarter of 2020 is primarily offset by inventory changes and timing of shipments in this quarter.

請參閱幻燈片 5。國際業務銷售額增長 9%，北美業務增長 5%，推動銷售額增長 7%。2020 年第一季度 COVID-19 相關庫存的負面影響主要被本季度的庫存變化和發貨時間所抵消。

All therapy areas contributed to growth, with diabetes care sales growing by 9%, driven by GLP-1 sales growth and unchanged insulin sales. GLP-1 sales increased by 23%, driven by North America growing by 19% and international operations growing by 31%. The unchanged insulin sales were driven by 5% growth in international operations, offset by 10% sales decline in North America. The U.S. insulin sales declined by 10%, driven by declining in volume, rebate enhancement, while partially offset by channel mix. Diabetes care sales grew by 9% as international operations grew by 18%, and North America operations grew by 2%. Biopharm sales increased by 1%, driven by North America operations.

所有治療領域都對增長做出了貢獻，在 GLP-1 銷售增長和胰島素銷售不變的推動下，糖尿病護理銷售額增長了 9%。在北美增長 19% 和國際業務增長 31% 的推動下，GLP-1 銷售額增長了 23%。胰島素銷售額不變的原因是國際業務增長 5%，但被北美銷售額下降 10% 所抵消。由於銷量下降和回扣增強，美國胰島素銷售額下降了 10%，但渠道組合部分抵消了這一影響。糖尿病護理銷售額增長 9%，國際業務增長 18%，北美業務增長 2%。在北美業務的推動下，生物製藥銷售額增長了 1%。

Please turn to Slide 6. In line with our strategic (technical difficulty) of reaching 1/3 of the diabetes value market by 2025, we have improved our market share by 0.6 percentage points to 29.3%. The increase reflects GLP-1 market share gains in both operating units. We have increased our insulin volume market share to 47.3%, driven by market share gains in international operations, supported by all 3 areas.

請參閱幻燈片 6。按照我們到 2025 年達到糖尿病價值市場 1/3 的戰略（技術難度），我們的市場份額提高了 0.6 個百分點，達到 29.3%。這一增長反映了兩個運營部門 GLP-1 市場份額的增長。在國際業務市場份額增長的推動下，在所有 3 個領域的支持下，我們的胰島素銷量市場份額已增加至 47.3%。

Please turn to slide 7. The U.S. GLP-1 volume market is around -- sorry, the US GLP-1 volume market growth is around 20% in the first quarter of 2021 driven by once-weekly injectable as well as oral GLP-1 products. Novo Nordisk market leadership is now 58%, driven by the uptake of Ozempic and supported by Rybelsus. Measured on total scripts, Novo Nordisk is the market leader with more than 50% market share.

請翻至幻燈片 7。美國 GLP-1 銷量市場即將到來——抱歉，在每週一次的注射劑和口服 GLP-1 的推動下，美國 GLP-1 銷量市場在 2021 年第一季度增長約 20%產品。在 Ozempic 的普及和 Rybelsus 的支持下，諾和諾德 (Novo Nordisk) 的市場領先地位目前為 58%。從總腳本數來看，諾和諾德是市場領導者，擁有超過 50% 的市場份額。

Please turn to Slide 8. In the U.S., Rybelsus increases its volume market share, both in terms of total scripts and new patient starts despite 2 lockdowns with no face-to-face interactions between Novo Nordisk and the prescribers. We have secured broad market access for Rybelsus while the majority of Rybelsus scripts are now reimbursed, and more than 80% of new patients are from outside the GLP-1 class.

請參閱幻燈片 8。在美國，儘管諾和諾德與處方醫生之間沒有面對面互動的兩次封鎖，但 Rybelsus 在總處方數和新患者開始數量方面都增加了其銷量市場份額。我們已經確保了 Rybelsus 的廣泛市場准入，同時大多數 Rybelsus 藥物現已報銷，並且超過 80% 的新患者來自 GLP-1 類別以外的患者。

Outside of the U.S., Rybelsus has now been launched in 14 countries with 1 key market being Japan. 2.5 months into the launch, Rybelsus has captured 0.5% of the all anti-diabetes market. The OAD market in Japan constitutes around 80% of the diabetes market.

Rybelsus 現已在美國以外的 14 個國家/地區上市，其中日本是其中 1 個主要市場。上市 2.5 個月後，Rybelsus 佔據了所有抗糖尿病藥物市場 0.5% 的份額。日本的 OAD 市場約佔糖尿病市場的 80%。

Please go to slide 9. In international operations, diabetes care sales increased by 10%, driven by all geographies. The continued rollout of new generation insulins and focus on the GLP-1 product portfolio has resulted in an increased diabetes market share, which is now 23.6%. This is driven by share -- market share gains in both GLP-1 and insulin. The value share of the GLP-1 class of the total diabetes market has increased 1.8 percentage points to 11.2%.

請轉至幻燈片 9。在國際業務中，在所有地區的推動下，糖尿病護理銷售額增長了 10%。新一代胰島素的持續推出以及對 GLP-1 產品組合的關注導致糖尿病市場份額增加，目前已達到 23.6%。這是由 GLP-1 和胰島素的市場份額增長所驅動的。GLP-1 類藥物在整個糖尿病市場的價值份額增加了 1.8 個百分點，達到 11.2%。

Please turn to Slide 10. Obesity care sales increased by 9% with 2% growth in North America operations and 18% growth in international operations. Throughout 2020 and into '21, fewer patients have started treatment with Saxenda due to COVID-19 lockdown and reduced access to health care providers. In the U.S., we have since the start of the year seeing an upward trend in the new patient starts on Saxenda, indicating early signs of recovery in patient flow.

請翻到幻燈片 10。肥胖護理銷售額增長 9%，其中北美業務增長 2%，國際業務增長 18%。整個 2020 年和進入 21 世紀，由於 COVID-19 封鎖以及醫療保健提供者的獲取機會減少，開始接受 Saxenda 治療的患者數量減少。在美國，自今年年初以來，我們看到 Saxenda 開始治療的新患者數量呈上升趨勢，這表明患者流量恢復的早期跡象。

Please turn to Slide 11. Biopharm sales grew by 1%, driven by 3% sales growth in North America operations and unchanged sales in international operations. Rare blood disorders grew by 2%, driven by new product launches with Esperoct and Refixia. The 2% NovoSeven sales decline was more than offset by Hemophilia A product growing by 16% and Hemophilia B sales increasing by 18%. Rare endocrine disorders grew by 2%, driven by new indications and global rollout of next-generation device for Norditropin. Now over to you, Martin, for an update on R&D.

請翻到幻燈片 11。受北美業務銷售額增長 3% 和國際業務銷售額不變的推動，生物製藥銷售額增長 1%。在 Esperoct 和 Refixia 新產品推出的推動下，罕見血液疾病增長了 2%。NovoSeven 銷售額下降 2%，但被血友病 A 產品增長 16% 和血友病 B 銷售額增長 18% 所抵消。在新適應症和下一代 Norditropin 設備在全球推出的推動下，罕見內分泌疾病增長了 2%。馬丁，現在請您了解研發方面的最新情況。

Thank you, Lars. Please turn to Slide 12. We continue to progress our late-stage pipeline, aiming at initiating Phase III activities across all of our therapy areas over the next year. In other serious chronic diseases, we in April initiated the Phase IIIa trial called Essence, evaluating subcutaneous once-weekly semaglutide 2.4 milligram for treatment of non-alcoholic steatohepatitis, or NASH. The trial will enroll around 1,200 people with NASH in Stages 2 and 3 of fibrosis.

謝謝你，拉爾斯。請翻到幻燈片 12。我們繼續推進我們的後期產品線，旨在明年在我們所有治療領域啟動 III 期活動。在其他嚴重慢性疾病方面，我們於 4 月份啟動了名為 Essence 的 IIIa 期試驗，評估每週一次皮下注射 2.4 毫克索馬魯肽治療非酒精性脂肪性肝炎 (NASH)。該試驗將招募約 1,200 名處於纖維化第 2 和第 3 階段的 NASH 患者。

The trial is planned in 2 parts. Part 1 will assess the effect of semaglutide 2.4 milligram versus placebo, both on top of standard of care. The primary assessment will be based on liver histology after 72 weeks of treatment. Part 2 will be an extension of part 1, thereby preserving the randomization and assessing the effect of semaglutide 2.4 milligram on liver-related clinical outcomes after a total of 240 weeks of treatment. The regulatory submission is expected to be based on part 1 of the trial, combined with the already completed and reported results from the Phase II trial for which we have been granted breakthrough designation by the U.S. FDA back in 2020.

該試驗計劃分兩部分進行。第 1 部分將評估 2.4 毫克索馬魯肽與安慰劑的效果，兩者均基於標準護理。主要評估將基於治療 72 週後的肝臟組織學。第 2 部分將是第 1 部分的延伸，從而保留隨機性並評估 2.4 毫克索馬魯肽在總共 240 周治療後對肝臟相關臨床結果的影響。監管提交預計將基於試驗的第 1 部分，並結合已完成並報告的 II 期試驗結果，我們已於 2020 年獲得美國 FDA 授予的突破性指定。

Please turn to the next slide. In obesity, our strategic aspiration is to develop a leading portfolio of superior treatment solutions. Consequently, we've decided to complement our injectable therapy portfolio with an oral option. From market research, we know that the majority of people with overweight seeking care with health care providers are not referred to an anti-obesity medicines prescriber. Further, research has shown that a number of patients as well as their prescribers have a preference for tablet-based treatment.

請翻到下一張幻燈片。在肥胖方面，我們的戰略願望是開發領先的優質治療解決方案組合。因此，我們決定通過口服選擇來補充我們的注射治療組合。根據市場研究，我們知道大多數向醫療保健提供者尋求治療的超重患者並沒有被轉介給抗肥胖藥物處方者。此外，研究表明，許多患者及其處方者偏愛基於片劑的治療。

Consequently, we expect to be able to address a substantial unmet need by developing a broader palette of obesity offerings as we enable announced our decision to enter into Phase III in obesity with all semaglutide 50 milligram. This decision follows the completion of the step Phase IIIa clinical program for once-weekly subcutaneous semaglutide 2.4 milligram which is currently under regulatory review in the U.S. as well as in the EU.

因此，當我們宣布決定進入肥胖症 III 期時，我們希望能夠通過開發更廣泛的肥胖產品來解決大量未滿足的需求，所有索馬魯肽 50 毫克。該決定是在完成每週一次皮下注射 2.4 毫克索馬魯肽的 IIIa 期臨床計劃之後做出的，該計劃目前正在美國和歐盟接受監管審查。

The global 68-week program, also called Oasis, will enroll around 1,000 people with obesity or overweight with at least 1 weight related comorbidity in a total of 3 trials. As usual, weight related comorbidities are defined as hypertension, dyslipidemia, obstructive sleep apnea and cardiovascular disease. We expect to end the second half of '21 to initiate the first of the 3 trials, which is expected to enroll around 650 trial participants. The objective is to confirm superiority of oral semaglutide 50-milligram versus placebo on weight loss in people with obesity or overweight.

這項為期 68 週的全球計劃也稱為 Oasis，將在總共 3 項試驗中招募約 1,000 名患有至少 1 種體重相關合併症的肥胖或超重患者。與往常一樣，與體重相關的合併症被定義為高血壓、血脂異常、阻塞性睡眠呼吸暫停和心血管疾病。我們預計將於 21 年下半年啟動 3 項試驗中的第一項，預計將招募約 650 名試驗參與者。目的是確認口服 50 毫克索馬魯肽與安慰劑相比，對於肥胖或超重患者的減肥效果更佳。

Please turn to the next slide. Now turning to the broader R&D high-level milestones in '21. As Lars mentioned earlier, we have in U.S. in March received a refusal to file letter for the label expansion for 2.0 milligram of Ozempic for the treatment of diabetes. The regulatory file was based on the SUSTAIN FORTE trial. The U.S. has requested additional information mainly related to additional manufacturing data. And it is our belief that no additional clinical data will be needed for the resubmission. We're currently in a constructive dialogue with the FDA and work to resubmit during the second quarter of '21.

請翻到下一張幻燈片。現在轉向 21 年更廣泛的研發高層里程碑。正如 Lars 之前提到的，我們 3 月份在美國收到了一封拒絕提交用於治療糖尿病的 2.0 毫克 Ozempic 標籤擴展的信函。該監管文件基於 SUSTAIN FORTE 試驗。美國已要求提供主要與額外製造數據相關的額外信息。我們相信重新提交不需要額外的臨床數據。我們目前正在與 FDA 進行建設性對話，並努力在 2021 年第二季度重新提交。

Moving on, also in the first quarter of '21, we have initiated a Phase III, 52-week clinical trial with once-weekly semaglutide 2.4 milligram in people with obesity related heart failure with preserved ejection fraction, also called HFpEF. In the second quarter, we also expect to initiate the Phase III program for oral semaglutide in Alzheimer's disease, and we look forward to receiving the feedback from the U.S. FDA on the application for semaglutide 2.4 milligram in obesity.

同樣在 21 年第一季度，我們啟動了一項為期 52 週的 III 期臨床試驗，每週一次 2.4 毫克索馬魯肽，治療射血分數保留的肥胖相關心力衰竭（也稱為 HFpEF）患者。第二季度，我們還預計啟動口服索馬魯肽治療阿爾茨海默病的III期項目，我們期待收到美國FDA關於索馬魯肽2.4毫克治療肥胖症申請的反饋。

Moving to the second half of '21, we expect to see Phase I results within our insulin innovation. And we also expect to initiate the Phase III outcomes trials for ziltivekimab within cardiovascular disease. Towards the turn of the year, we expect a decision from the EU on semaglutide 2.4 milligram in obesity as well as for Ozempic 2.0 milligram within diabetes. And within biopharm, we expect to have results from the Phase III program for somapacitan in children.

進入 21 年下半年，我們預計將看到胰島素創新的第一階段成果。我們還預計啟動 ziltivekimab 在心血管疾病領域的 III 期結果試驗。在今年年初，我們預計歐盟將就肥胖症患者服用 2.4 毫克索馬魯肽以及糖尿病患者服用 2.0 毫克 Ozempic 做出決定。在生物製藥領域，我們預計兒童 somapacitan 的 III 期項目將取得結果。

Lastly, for the ongoing combined Phase I and II trial with Mim8, we expect to see results from the different cohorts during the coming 3 quarters. With that, over to you, Karsten.

最後，對於正在進行的 Mim8 的 I 期和 II 期聯合試驗，我們預計在未來 3 個季度內看到不同隊列的結果。就這樣，交給你了，卡斯滕。

Thank you, Martin. Please turn to Slide 15. In the first 3 months of 2021, sales were unchanged in Danish kroner and grew by 7% at constant exchange rates. The gross margin declined to 82.8% compared to 84.1% in 2020. The decline reflects negative currency impact and lower realized prices in the U.S., partly offset by positive product mix and productivity. Sales and distribution costs increased by 9% in Danish kroner and 16% at constant exchange rates. The increase is driven by launch activities and promotional spend for Rybelsus and Ozempic, market development investments for obesity, as well as sales force expansions in China.

謝謝你，馬丁。請翻到幻燈片 15。2021 年前 3 個月，以丹麥克朗計算的銷售額保持不變，按固定匯率計算增長了 7%。毛利率由2020年的84.1%下降至82.8%。這一下降反映了貨幣的負面影響和美國實際價格的下降，但部分被積極的產品組合和生產率所抵消。以丹麥克朗計算的銷售和分銷成本增加了 9%，以固定匯率計算則增加了 16%。這一增長的推動因素包括 Rybelsus 和 Ozempic 的上市活動和促銷支出、針對肥胖症的市場開發投資以及中國銷售隊伍的擴張。

Research and development costs increased by 4% in Danish kroner and 7% at constant exchange rates. The cost increase is driven by a higher activity level as we progressed the early-stage pipeline within other serious chronic diseases, as well as the ongoing cardiovascular outcome trials, SOUL and SELECT. Administration costs increased by 1% in Danish kroner and 3% at constant exchange rates.

以丹麥克朗計算的研發成本增加了 4%，以固定匯率計算則增加了 7%。隨著我們在其他嚴重慢性疾病的早期研發管線以及正在進行的心血管結果試驗 SOUL 和 SELECT 中取得進展，更高的活動水平推動了成本增加。以丹麥克朗計算的管理成本增加了 1%，以固定匯率計算則增加了 3%。

Operating profit decreased by 8% in Danish kroner and increased by 3% at constant exchange rates. The negative currency impact on operating profit is partly offset by around DKK 1 billion in hedging gains under net financial items. This compares to a loss of DKK 1.3 billion in 2020. The hedging gains are a consequence of the U.S. dollar trading 9% lower compared to last year. Net profit increased by 6% and diluted earnings per share increased by 8% to DKK 5.45. Free cash flow was DKK 9.5 billion compared to DKK 7.7 billion in 2020. The increase reflects the higher net profit and the favorable impact from changes in working capital.

以丹麥克朗計算的營業利潤下降了 8%，以固定匯率計算則增長了 3%。貨幣對營業利潤的負面影響被淨金融項目下約 10 億丹麥克朗的對沖收益部分抵消。相比之下，2020 年損失為 13 億丹麥克朗。對沖收益是美元匯率較去年下跌 9% 的結果。淨利潤增長 6%，攤薄後每股收益增長 8%，達到 5.45 丹麥克朗。自由現金流為 95 億丹麥克朗，而 2020 年為 77 億丹麥克朗。這一增長反映了淨利潤的增加以及營運資金變化的有利影響。

Please turn to slide 16. In the first quarter of 2021, we have realized a negative currency impact on sales and operating profits. The currency headwinds are driven by most major currencies and emerging market currencies trading at lower levels in 2021 than in 2020. Some of the negative currency impact from major currencies on operating profit is, as mentioned, partly offset in net financial items as they are hedged.

請翻到幻燈片 16。2021 年第一季度，我們意識到匯率對銷售和營業利潤產生了負面影響。貨幣逆風是由大多數主要貨幣和新興市場貨幣在 2021 年的交易水平低於 2020 年造成的。如前所述，主要貨幣對營業利潤的一些負面影響在淨金融項目中被部分抵消，因為它們是對沖的。

Please turn to the next slide. Based on the strong underlying performance seen in the beginning of 2021, we now expect 2021 sales growth between 6% and 10% at constant exchange rates. This guidance reflects continued diabetes care growth, mainly driven by Ozempic and Rybelsus as well as obesity care growth. Also embedded is intensifying competition both within diabetes care and biopharm and continued pricing pressure, mainly within diabetes care in the U.S.

請翻到下一張幻燈片。基於 2021 年初強勁的基本表現，我們現在預計按固定匯率計算，2021 年的銷售額增長在 6% 至 10% 之間。該指導反映了糖尿病護理的持續增長，主要由 Ozempic 和 Rybelsus 以及肥胖護理增長推動。此外，糖尿病護理和生物製藥領域的競爭加劇，以及持續的定價壓力（主要是美國的糖尿病護理領域）。

Operating profit is now expected to grow between 5% and 9%, reflecting the sales growth outlook and continued investments in current growth drivers as well as pipeline assets to secure future growth. As previously mentioned, we expect negative currency impact for the full year. Consequently, reported sales and operating profit growth is now still expected to be 4% and 6% lower than at constant exchange rates, respectively.

目前預計營業利潤將增長 5% 至 9%，反映了銷售增長前景以及對當前增長動力和管道資產的持續投資，以確保未來增長。如前所述，我們預計全年的匯率將受到負面影響。因此，目前預計報告的銷售額和營業利潤增長仍將比按固定匯率計算分別低 4% 和 6%。

The current COVID-19 pandemic causes uncertainty to the outlook regarding new patient initiations and societal impacts. Financial items is still expected to be a gain of around DKK 0.7 billion. Due to minor timing changes, we now expect capital expenditure to be around DKK 7.5 billion in 2021. Lastly, free cash flow is parallel shifted upwards by DKK 1 billion and now expected to be between DKK 37 billion and DKK 42 billion. As a consequence, the ongoing share buyback program is expanded with DKK 1 billion to DKK 18 billion. Now back to you, Lars, for final remarks.

當前的 COVID-19 大流行給新患者入院和社會影響的前景帶來了不確定性。金融項目預計仍將獲得約 7 億丹麥克朗的收益。由於時間安排上的細微變化，我們目前預計 2021 年的資本支出約為 75 億丹麥克朗。最後，自由現金流平行上調 10 億丹麥克朗，目前預計在 370 億丹麥克朗至 420 億丹麥克朗之間。因此，正在進行的股票回購計劃從 10 億丹麥克朗擴大到 180 億丹麥克朗。現在回到你，拉斯，最後發言。

Thank you, Karsten. Please turn to slide 18. We are very encouraged with the start of the year. Sales growth was driven by all therapy areas and across geographical areas within international operations as well as North America operations, where growth was accelerated in the U.S. We were also pleased to announce plans to develop oral semaglutide as a convenient and effective treatment option for people with obesity, complementing our injectable obesity medications. The solid financial performance in the first 3 months of 2021 has enabled us to raise our outlook range for the full year.

謝謝你，卡斯滕。請翻到幻燈片 18。今年伊始，我們深受鼓舞。銷售增長是由國際業務以及北美業務中的所有治療領域和跨地理區域推動的，其中美國的增長加速。我們還很高興地宣布計劃開發口服索馬魯肽，作為患有以下疾病的人的一種方便而有效的治療選擇肥胖，補充我們的注射肥胖藥物。2021 年前 3 個月穩健的財務表現使我們能夠上調全年展望範圍。

We're now ready for the Q&A, where I kindly ask all participants to leave for her or himself to 2 questions. Operator, we're now ready to take the first questions.

現在我們已經準備好進行問答了，我懇請所有參與者留給自己兩個問題。接線員，我們現在準備好回答第一個問題。

(Operator Instructions) Our first question comes from Emmanuel Papadakis from Deutsche Bank.

（操作員說明）我們的第一個問題來自德意志銀行的 Emmanuel Papadakis。

Emmanuel Papadakis from Deutsche Bank. Since I'm early, perhaps I'll start with a guidance question. Seems majority of the Q1 revenue beat was stocking related. Perhaps you could just quantify that. And you notably raised guidance regardless. So if you could just talk about the confidence in that stocking you saw in Q1, the revenue side will not reverse through the course of this year? And whether there are any other factors driving your increased confidence for the full-year outlook or indeed any other swing factors we should be thinking about in terms of the range for this year.

德意志銀行的伊曼紐爾·帕帕達基斯。由於我來得早，也許我會先提出一個指導性問題。第一季度收入增長的大部分似乎與庫存有關。也許你可以量化這一點。不管怎樣，你都特別提出了指導意見。那麼，如果您能談談對第一季度庫存的信心，那麼今年的收入方面不會出現逆轉嗎？以及是否有任何其他因素促使您對全年前景信心增強，或者我們應該在今年的範圍內考慮任何其他波動因素。

And then perhaps I'll take a question around the outlook in China. What have you assumed, if anything, at present in your guidance for potential VBP incident impact? It appears possible it still could come within 2021. What are your latest expectations around timing and price impact? And what options would be available to you to mitigate that at the EBIT level were it to arrive?

然後也許我會問一個有關中國前景的問題。您目前在針對潛在 VBP 事件影響的指南中有何假設（如果有的話）？看來它仍有可能在 2021 年實現。您對時間和價格影響的最新預期是什麼？如果它到來，您可以採取哪些選項來減輕息稅前利潤水平上的影響？

Thank you, Emmanuel. 2 questions related to guidance. One linked to the stocking we saw and what more to say about the guidance lift. And then outlook for China also in -- linked to guidance and volume-based pricing. So Karsten, over to you.

謝謝你，伊曼紐爾。2個與指導相關的問題。其中一個與我們看到的庫存有關，還有關於引導升降機的更多內容。中國的前景也與指導和基於數量的定價有關。那麼卡斯滕，交給你了。

Yes. Thank you for those questions, Emmanuel. And clearly, some movements on Q1 results, that's important to take into account when providing full-year guidance. So just to reiterate, our 7% sales growth in the first quarter should be considered in the light of the DKK 2 billion stocking we saw in the first quarter last year. So if adjusting for that would take us to 14% sales growth. And then what we saw in the first quarter of this year between wholesaler stocking in the U.S., partly related to launch of Ozempic with the 3 ml cartridges as 1 piece. And then timing of shipments in [IO and tenders] as well, would basically adjust the (technical difficulty) sales growth down to 9%.

是的。謝謝你提出這些問題，伊曼紐爾。顯然，在提供全年指導時，必須考慮第一季度業績的一些變化。因此，重申一下，我們第一季度 7% 的銷售增長應該根據去年第一季度 20 億丹麥克朗的庫存來考慮。因此，如果對此進行調整，我們的銷售額將增長 14%。然後我們今年第一季度在美國批發商的庫存中看到的情況，部分與 Ozempic 的推出有關，其中 3 毫升墨盒為 1 件。然後 [IO 和招標] 的發貨時間也基本上會將（技術難度）銷售增長調整至 9%。

So in adjusted terms, our Q1 underlying sales growth is 9% and that's basically in the high end of the guidance range we issued back in February, where we said from 5% to 9%, and being in the high end was one of the key indicators for us to increase our full-year guidance. On top of that, linking to your China impact to guidance question. Then, of course, when assessing the proper guidance for the remainder -- for the full year, of course, that also takes into account the risk picture we're looking into. And what we see in China specifically is that we do see an impact from volume-based purchasing on NovoNorm, so the so-called [VBP 4], where we'll see an impact on NovoNorm starting from May and onwards. So that's fully included into our guidance.

因此，按調整後的計算，我們第一季度的基本銷售增長率為9%，這基本上處於我們2 月份發布的指導範圍的高端，我們說從5% 到9%，而處於高端是我們的目標之一。我們提高全年指導的關鍵指標。最重要的是，將您的中國影響與指導問題聯繫起來。當然，在評估剩餘時間（全年）的適當指導時，當然也會考慮到我們正在研究的風險狀況。我們在中國看到的具體情況是，我們確實看到了基於數量的採購對 NovoNorm 的影響，即所謂的 [VBP 4]，我們將從 5 月份開始看到對 NovoNorm 的影響。因此，這已完全納入我們的指南中。

In terms of pursuing VBPs in China, we do not expect insulin to be included in VBP 5, which is happening now with effect from some time in Q3. And hence, any potential impact from insulin on volume-based pricing in China would be later in the year. So truly quantifying that is hard because we don't know the exact structure and timing. But that's also why we're working with guidance ranges. So it can be bigger, smaller, but we do expect a negative impact in the time to come from insulin in China.

就在中國推行 VBP 而言，我們預計胰島素不會被納入 VBP 5，目前這種情況正在發生，並從第三季度的某個時間開始生效。因此，胰島素對中國基於數量的定價的任何潛在影響都將在今年晚些時候出現。因此真正量化這一點很困難，因為我們不知道確切的結構和時間。但這也是我們採用指導範圍的原因。所以它可以更大，也可以更小，但我們確實預計胰島素在中國將會產生負面影響。

Our next question comes from Peter Verdult from Citi.

我們的下一個問題來自花旗銀行的 Peter Verdult。

Pete Verdult, Citi. Two Questions. Mads -- sorry, Karsten. Simple one, just tax, what the implications would be if U.S. goes to 28%? Realize it won't have an impact on '21, but just going forward, any sort of sensitivities there would be helpful. And then assuming Camilla is on the line. Could you just remind us how big the current U.S. Saxenda sales force is and your current approach to the launch? Should we be thinking sort of omnichannel approach? Or are you particularly focusing on either widening the prescriber base, getting patients to seek treatment initially or to improve the reimbursement access? Or are you trying to do all things at the same time? So anything you're willing to share at this juncture would be appreciated.

皮特·韋爾多，花旗銀行。兩個問題。麥茲——對不起，卡斯滕。很簡單，就是徵稅，如果美國達到28%，會產生什麼影響？意識到這不會對 21 年產生影響，但展望未來，任何類型的敏感性都會有所幫助。然後假設卡米拉在線。您能否提醒我們目前 Saxenda 的美國銷售隊伍有多大以及您目前的發布方式？我們應該考慮某種全渠道方法嗎？或者您是否特別關注擴大處方者基礎、讓患者首先尋求治療或改善報銷渠道？或者你想同時做所有的事情？因此，您此時願意分享的任何信息都將不勝感激。

Thank you, Pete. So first, Karsten, on impact from potential change in tax structure in the U.S. And then later on, Camilla?

謝謝你，皮特。那麼首先，卡斯滕，談談美國稅收結構潛在變化的影響。然後，卡米拉？

Yes. Thanks, Pete. That's clearly something we're looking at. So -- and as you know, it has not been concluded in Congress at this point. But I'll say the simple sensitivity measure on tax impact is that a -- and what we saw when the Trump administration reduced rates some years back, was that on the U.S. corporate income tax rate, if a reduction or a movement of 10 percentage point on that moves our global group effective tax rate by 1 percentage point.

是的。謝謝，皮特。這顯然是我們正在關注的事情。所以——正如你所知，國會目前尚未得出結論。但我要說的是，對稅收影響的簡單敏感性衡量標準是——幾年前特朗普政府降低稅率時，我們看到的是美國企業所得稅稅率，如果減少或變動 10%這將使我們的全球集團有效稅率提高1 個百分點。

So taking the U.S. rate from 21% to 28%, that would move our group rate by some 50 basis points or something like that. There are a number of other potential elements in the rule-making process. And I'm sure you read about global minimum taxes and so on. At this point, it's simply too early to assess whether it has an impact or not. But the simple sensitivity is around 0.5 percentage point from the U.S. corporate income tax.

因此，將美國的利率從 21% 提高到 28%，這將使我們的集團利率上升約 50 個基點或類似的幅度。規則制定過程中還有許多其他潛在因素。我確信您讀過有關全球最低稅等的內容。現在評估它是否有影響還為時過早。但簡單的敏感性約為美國企業所得稅的0.5個百分點。

Thank you, Karst. And then Camilla, what can you share in terms of tactics for the obesity commercial efforts in the U.S.?

謝謝你，卡斯特。那麼卡米拉，您可以分享一下美國肥胖商業活動的策略嗎？

Yes. So in terms of tactics for the obesity in the U.S., we are, of course, focused on driving the expansion in the commercial segment. But we're, of course, also working longer-term to get into the Medicare segment. This, of course, is not -- there is no sort of -- an immediate timeline to that. But what we can say about the access in the commercial segment is that there is -- we are working on making sure that there is opt into the gross coverage, meaning that we can improve also on our net coverage. And of course, we also expect that over time, when we launch our next product, semaglutide 2.4, subject to approval, that that will also, of course, be of -- effectful in terms of getting coverage. So coverage continues to be important.

是的。因此，就美國肥胖問題的策略而言，我們當然專注於推動商業領域的擴張。但當然，我們也在長期努力進入醫療保險領域。當然，這並不是——沒有任何一種——立即的時間表。但關於商業領域的接入，我們可以說的是——我們正在努力確保可以選擇進入總覆蓋範圍，這意味著我們也可以改善我們的淨覆蓋範圍。當然，我們還預計，隨著時間的推移，當我們推出下一個產品索馬魯肽 2.4 並獲得批准時，這當然也會在獲得覆蓋方面發揮作用。因此，覆蓋範圍仍然很重要。

And in terms of sales reps, we are complementing our efforts from sales reps with omnichannel approaches. And of course, also working to see if we can expand what we call the direct care approach. Which means that since there are very few physicians that are prescribing obesity products at this point, it might be easier to enable that with an omnichannel approach, meaning online diagnosis potentially over time and online scripts. So that's something that we are working on, but it's not in full force at this point in time.

在銷售代表方面，我們正在通過全渠道方法補充銷售代表的努力。當然，我們還要努力看看我們是否可以擴大所謂的直接護理方法。這意味著，由於目前很少有醫生開出肥胖產品的處方，因此通過全渠道方法可能更容易實現這一點，這意味著隨著時間的推移和在線腳本可能會進行在線診斷。所以這是我們正在努力的事情，但目前還沒有完全發揮作用。

Thank you, Camilla. Thank you, Pete. Next set of question please.

謝謝你，卡米拉。謝謝你，皮特。請提出下一組問題。

Our next question comes from Vimal Kapadia from Bernstein.

我們的下一個問題來自 Bernstein 的 Vimal Kapadia。

Wimal Kapadia from Bernstein. Can I just first ask on GLP-1 pricing, please? It seems that the net price of Rybelsus in the U.S. in 1Q was around $13.50 per day. That compares to closer to 20% -- $20 per day for Ozempic. So just curious if we now believe this is at a steady state from which future declines will appear. Or is there still some co-pay impact in Rybelsus, which will mean that the net price could be slightly higher for the rest of 2021?

伯恩斯坦的維馬爾·卡帕迪亞。我可以先詢問一下 GLP-1 的定價嗎？看來第一季度 Rybelsus 在美國的淨價約為每天 13.50 美元。相比之下，Ozempic 的費用接近 20%，即每天 20 美元。所以只是好奇我們現在是否相信這是一個穩定的狀態，未來會出現下降。或者 Rybelsus 是否仍然存在一些共付額影響，這意味著 2021 年剩餘時間的淨價可能會略高？

And then my second question is just following up on China and VBP again. I just wanted to get a sense of what is your current base assumption? When we eventually do see a VBP, how will it be implemented? Would it be the more traditional approach like the typical wave 5 and 6 in the future? Or could it be a Wuhan star VBP, which was clearly very different? And then just tied to that, any thoughts on a potential GLP-1 VBP at some point in the future? Would the Chinese government actually consider all GLP-1s in the same class like they did with the different incident classes?

我的第二個問題是再次跟進中國和 VBP。我只是想了解一下您當前的基本假設是什麼？當我們最終看到 VBP 時，它將如何實施？未來會是像典型的第 5 波和第 6 波那樣更傳統的方法嗎？或者它可能是一個明顯不同的武漢明星VBP？與此相關的是，對於未來某個時候潛在的 GLP-1 VBP 有什麼想法嗎？中國政府是否真的會將所有 GLP-1 視為同一類別，就像對待不同事件類別一樣？

Thank you, Wimal. So first, Karsten, on GLP-1 pricing?

謝謝你，維馬爾。Karsten，首先談談 GLP-1 的定價？

Yes. So on Rybelsus and GLP-1 pricing. So, Wimal, it's always dangerous to do this value per script on a quarterly basis. But I would say, in trying to make it as simple as possible then, when you compare Ozempic and Rybelsus, then there's a delta of 11% on a list price per day, simply due to the size of the script between a weekly and a daily treatment. So that's 1 delta. Then furthermore, we do see continued use of affordability programs for Rybelsus. So there's both a bigger co-pay buy down compared to that of Ozempic since we're competing in the oral segment, down to $10.

是的。關於 Rybelsus 和 GLP-1 的定價。因此，Wimal，每季度為每個腳本執行此值總是很危險的。但我想說的是，為了盡可能簡單，當你比較 Ozempic 和 Rybelsus 時，每天的標價有 11% 的增量，這僅僅是由於每周和每週之間的腳本大小所致。日常治療。所以這是 1 個增量。此外，我們確實看到 Rybelsus 繼續使用負擔能力計劃。因此，與 Ozempic 相比，由於我們在口腔領域競爭，因此共付費用降低至 10 美元。

And then we still see a sale of some of the affordability programs from 2020, where you have some runway before that ends. And then, of course, there's the usual channel mix dynamics, where you start out in the higher-margin channels and then over time, products are available in more channels also in lower-margin channels. So I'd say in short the affordability piece with the tail going out on some of the launch programs, that should be beneficial. But the channel mix, as we've seen it with other products, should be negative going forward on an ARP per script basis, but on a net value, it will be positive.

然後，我們仍然會看到從 2020 年開始出售一些負擔能力計劃，在此之前您還有一些跑道。當然，還有通常的渠道混合動態，即從利潤率較高的渠道開始，然後隨著時間的推移，產品可以在更多的渠道中使用，也可以在較低利潤的渠道中使用。所以我想說，簡而言之，在一些啟動計劃中，負擔能力部分應該是有益的。但是，正如我們在其他產品中看到的那樣，渠道組合在每個腳本的 ARP 基礎上應該是負值，但從淨值來看，它將是正值。

Thank you, Karsten. And on China, volume based pricing, we cannot really go in and speculate about what will happen in the future. I'll just say that I believe it's slightly more complicated to handle biological medicines for physicians and patients. If you go into these type tender situations compared to small molecules, while it's not really possible for us to speculate on how this will play out in the future. Thank you, Wimal. Next set of questions, please.

謝謝你，卡斯滕。對於中國，基於數量的定價，我們無法真正參與並推測未來會發生什麼。我只想說，我認為為醫生和患者處理生物藥品稍微複雜一些。與小分子相比，如果你進入這些類型的溫柔情況，雖然我們實際上不可能推測這在未來將如何發揮作用。謝謝你，維馬爾。請提出下一組問題。

Our next question comes from Jannick Lindegaard from ABG.

我們的下一個問題來自 ABG 的 Jannick Lindegaard。

It's Jannick Denholt from ABG. Can I ask a little about your maneuver room right now in the U.S. in terms of getting Rybelsus on the road? Essentially now this is the, what, third time you're trying to launch it with the field force coming in. So can you talk a little more about your field force interaction? So I understand that you are approaching some 85% or so of the core interactions with ACPs are face-to-face. How does that translate into productivity, i.e., in terms of usual number of calls that you make? And then secondly, also on Rybelsus rollout, then in Japan, obviously there's this 14-day limitation for the first year on prescription. So how should we think about the uptake in Japan this year? Because, obviously, longer term, this is a huge opportunity.

我是 ABG 的 Jannick Denholt。我能問一下你們現在在美國讓 Rybelsus 上路的迴旋餘地嗎？本質上，現在這是你第三次嘗試在現場部隊介入的情況下啟動它。那麼您能多談談您的現場人員互動嗎？據我了解，您與 ACP 的核心互動中大約 85% 左右是面對面的。這如何轉化為生產力，即您通常撥打的電話數量？其次，在 Rybelsus 推出時，在日本，顯然第一年的處方有 14 天的限制。那麼我們應該如何看待今年日本的使用情況呢？因為，顯然，從長遠來看，這是一個巨大的機會。

Thank you, Jannick. I'll pass on both questions to Camilla.

謝謝你，詹尼克。我會將這兩個問題轉達給卡米拉。

Thank you, Jannick. Yes, correct, that we are quite optimistic around when we get back into the field, we see that the -- that the NBRx curves of Rybelsus comes back to similar slopes of the curve, so to say. Of course, we are not fully, as you say, back in the field yet so there's still some room. But we are, of course, constantly increasing our presence in the field also. So -- and in 2020, we also got quite some experience on how to supplement our in-field presence with other types of multichannel engagement parameters. So that's the way that we try to do this. But over time, this constantly should increase also with the U.S. opening up.

謝謝你，詹尼克。是的，正確的，當我們回到現場時，我們非常樂觀，我們看到，Rybelsus 的 NBRx 曲線回到了相似的曲線斜率，可以這麼說。當然，正如您所說，我們還沒有完全回到現場，所以仍然有一些空間。當然，我們也在不斷增加我們在該領域的影響力。因此，在 2020 年，我們在如何通過其他類型的多渠道參與參數來補充我們的現場存在方面也獲得了相當多的經驗。這就是我們嘗試這樣做的方式。但隨著時間的推移，隨著美國的開放，這種情況也會不斷增加。

Then on Japan and Rybelsus rollout, we are quite satisfied with the uptake so far, especially when we look at also our share of voice, where we, together with Merck, have the highest share of voice in the OAD segment in Japan at this point in time. So despite the sort of special conditions in Japan with the 2-week prescription rules, then we feel that on a comparative note, we are tracking quite well in Japan following the very recent launch of Rybelsus.

然後，在日本和Rybelsus 的推出方面，我們對迄今為止的採用情況感到非常滿意，特別是當我們還考慮我們的話語權份額時，我們與默克一起在日本的OAD 細分市場中擁有最高的話語權份額及時。因此，儘管日本存在兩周處方規則的特殊情況，但我們認為，相比之下，在最近推出 Rybelsus 後，我們在日本的跟踪情況相當好。

Thank you, Camilla. And thank you, Jannick. So also as you can hear, we're very confident and very pleased with how Rybelsus is performing both in the U.S. and Japan, and we are very optimistic about the future for Rybelsus. Next set of questions, please.

謝謝你，卡米拉。謝謝你，詹尼克。正如您所聽到的，我們對 Rybelsus 在美國和日本的表現非常有信心和非常滿意，我們對 Rybelsus 的未來非常樂觀。請提出下一組問題。

Next question comes from Simon Baker from Redburn.

下一個問題來自 Redburn 的 Simon Baker。

Thanks for taking my questions. 2, please. Firstly, on phasing. I wonder if you could give us any pointers as to the phasing of R&D and SG&A costs across the remaining 3 quarters? Is there any things we should remember in terms of trial starts and launch costs? And also on phasing, if you could remind us on the COVID stocking, destocking for last year. Obviously, it was DKK 2 billion in Q1, DKK 500 million destocking in Q2. If you could just remind us what the Q3 and 4 impact was.

感謝您回答我的問題。2、請。首先，關於階段性。我想知道您能否就剩餘 3 個季度的研發和 SG&A 成本的分階段問題向我們提供任何建議？在試用開始和啟動成本方面有什麼我們應該記住的事情嗎？還有關於分階段的問題，請您提醒我們去年的新冠疫情庫存和去庫存情況。顯然，第一季度去庫存20億丹麥克朗，第二季度去庫存5億丹麥克朗。如果您能提醒我們第三季度和第四季度的影響是什麼。

And then secondly, on obesity, I wonder, as you're moving into supplement injectable with oral, if you could give us any thoughts on the potential payer and reimbursement challenges of oral versus injectable. There's long been a suggestion in some quarters that payers are probably more [receptible] to an injectable because it's seen as a "more serious medical intervention" then a pill. Is that your belief? And are there any things we should be thinking about in the future?

其次，關於肥胖，我想知道，當您轉向口服補充劑注射劑時，您能否給我們關於口服與註射劑的潛在付款人和報銷挑戰的任何想法。長期以來，某些方面一直有人認為，付款人可能更容易接受注射劑，因為它被視為比藥丸“更嚴重的醫療干預措施”。這是你的信仰嗎？未來有什麼值得我們思考的事情嗎？

Thank you, Simon. First, Karsten, on phasing, both on cost and stocking.

謝謝你，西蒙。首先，卡斯滕談到分階段，包括成本和庫存。

Yes. Thank you, Simon, for that set of questions. So on phasing, I would say the key aspect we'll be looking out for in terms of comparables versus last year, is in Q2, where we saw quite significant destocking last year, taking our Q2 sales growth last year, down to basically 0. So of course, that will impact the comparator as we saw impacting the comparator in the first quarter of this year, the other way around. So that would be the main on sales growth. I think on the other partial destocking between Q3 and Q4 last year, I think it will be on the decimal. So I wouldn't be [haunching] that vis-à-vis other impacts on top line.

是的。謝謝西蒙提出這一系列問題。因此，在分階段方面，我想說，我們在與去年相比的可比性方面要關注的關鍵方面是在第二季度，去年我們看到了相當大的去庫存，使去年第二季度的銷售增長降至基本為 0 .因此，這當然會影響比較器，就像我們在今年第一季度看到的那樣影響比較器，反之亦然。因此，這將是銷售增長的主要因素。我認為去年第三季度和第四季度之間的另一部分去庫存，我認為將會是小數點。因此，我不會[擔心]這會對營收產生其他影響。

In terms of our spending, I would say you should not expect any significant changes to our spending pattern this year. So the way it happens, I would say, if I take R&D first, then we're basically phasing our spending vis-à-vis the trial execution. So there's a start-up cost and a close down cost, and the remainder of the spending on trials are basically spread over the lifetime of the trial. And hence, it's being phased rather gradually. Then there would only be significant bumps in case of, you could say, any impairments to intangible assets. And as you know, we don't have a lot of acquired assets in Novo Nordisk, so don't expect significant bumps on -- in terms of R&D spending.

就我們的支出而言，我想說，今年我們的支出模式不會發生任何重大變化。因此，我想說的是，如果我首先進行研發，那麼我們基本上會分階段進行試驗執行的支出。因此，存在啟動成本和關閉成本，剩餘的試驗支出基本上分佈在試驗的整個生命週期中。因此，它正在逐步分階段進行。那麼，只有在無形資產出現任何減值的情況下才會出現顯著的波動。如您所知，我們在諾和諾德收購的資產並不多，因此在研發支出方面預計不會出現大幅增長。

S&D, what you saw here in the first quarter with S&D being up 16%, that was an artifact of us both pushing Rybelsus and Ozempic, especially in the U.S. market from the beginning. So we're basically running parallel DTC campaigns behind the brands. So we've front-loaded the spending. But more granularity in terms of the phasing I would not want to give at this point in time because that also indicates some of our commercial tactics vis-à-vis, for instance, DTC programs in the U.S.

S&D，您在第一季度看到的 S&D 增長了 16%，這是我們推動 Rybelsus 和 Ozempic 的成果，尤其是從一開始就在美國市場。因此，我們基本上是在品牌背後開展並行的 DTC 活動。因此，我們預先增加了支出。但目前我不想提供更詳細的分階段信息，因為這也表明了我們針對美國 DTC 項目等的一些商業策略。

Thank you, Karsten. And on payer reception of oral sema in obesity, we're starting the trial now. So maybe it's a bit early to start talking about market access. But I would just make the comment that we see that for Rybelsus, which is an oral version of sema, we see pricing similar to what we see on Ozempic. So I think this is all about efficacy. And bear in mind that the obesity market is, say, a market to be opened up. And I think there is plenty of opportunity to segment that market. And I'm sure that there's a very large segment who would prefer an oral treatment. So for us, that's a significant opportunity.

謝謝你，卡斯滕。關於付款人接受肥胖症口腔塞瑪的情況，我們現在開始試驗。因此，也許現在開始談論市場准入還為時過早。但我只想評論說，我們看到 Rybelsus（sema 的口頭版本）的定價與 Ozempic 類似。所以我認為這一切都與功效有關。請記住，肥胖市場是一個有待開放的市場。我認為有很多機會來細分這個市場。我確信有很大一部分人更喜歡口服治療。所以對我們來說，這是一個重要的機會。

Our next question comes from Trung Huynh from Credit Suisse.

我們的下一個問題來自瑞士信貸銀行的 Trung Huynh。

It's Trung Huynh from Credit Suisse. Three questions, if I can. First one, oral sema and obesity. The 50 mg dose that you're going for is a 25x more than the injectable sema dose for obesity. So I know you're working on improvements in yield, but how should we think about the gross margin impact of this in the short-term but also the long term?

我是瑞士信貸銀行的 Trung Huynh。三個問題，如果可以的話。第一個，口腔水腫和肥胖。您需要的 50 毫克劑量比治療肥胖症的注射血清劑量高 25 倍。所以我知道你們正在努力提高產量，但我們應該如何考慮這對短期和長期毛利率的影響？

Secondly, you initiated the study of sema in obesity with HFpEF. So perhaps, can you discuss some of the rationale for starting this study, maybe the commercial opportunity you have there? Is there any opportunity to move beyond the obesity in diabetes patients?

其次，您發起了 HFpEF 肥胖症的 sema 研究。那麼，也許您可​​以討論一下開始這項研究的一些理由，也許您在那裡擁有商業機會？糖尿病患者是否有機會擺脫肥胖的困擾？

And then finally, just on Mim8, the Phase I/II results now are listed as 2Q to 2H. Just seeing if that's somewhat a slight delay there? Or are we expecting multiple data sets throughout this year?

最後，就在 Mim8 上，I/II 期結果現在列為 2Q 到 2H。只是看看這是否有點輕微的延遲？或者我們預計今年會有多個數據集？

So thank you, Trung Huynh. So first, Karsten, on the 50 mg gross margin impact.

謝謝你，Trung Huynh。首先，Karsten，關於 50 毫克毛利率的影響。

Yes. Thank you for pointing to that trial, Trung, because that's actually one of my favorite trials these days. Because actually, what you're looking at is a Phase III asset that only takes 1,000 patients in clinical trials -- in the clinical trials to get to a regulatory decision. So our cost to get to market is, in the first place, relatively manageable compared to most other Phase III programs.

是的。謝謝你指出那個試驗，Trung，因為這實際上是我這些天最喜歡的試驗之一。因為實際上，您看到的是一項 III 期資產，只需要 1,000 名患者參與臨床試驗——在臨床試驗中就可以做出監管決定。因此，與大多數其他第三階段項目相比，我們進入市場的成本首先是相對可控的。

Then in terms of commercialization, you know all about the volume opportunity in obesity and the attractiveness of having an asset with an efficacy in the magnitude of what we see with the sema 2.4 and up to 18% weight loss as we saw in the STEP program. And of course, before entertaining such a trial, then we do a lot of financial modeling, including cost of goods and manufacturing.

然後在商業化方面，您了解肥胖症的數量機會，以及擁有我們在 sema 2.4 中看到的功效和高達 18% 的減肥效果（正如我們在 STEP 計劃中看到的那樣）的資產的吸引力。 。當然，在進行這樣的試驗之前，我們會進行大量的財務建模，包括商品和製造成本。

And I would say with the scaling we're doing in our manufacturing setup and the process improvement we are entertaining in manufacturing, first of all, we do see improvements in our cost of goods, as we've also been discussing with Rybelsus early on. Furthermore, what we're also doing is that we're looking at the formulation of the tablets in the 50-milligram version, thereby also looking at certain opportunities in terms of improving our gross margin profile for the product. So all in all, we expect to see an attractive product on -- also on a gross margin level if and when we get to market.

我想說的是，隨著我們在製造設置中所做的擴展以及我們在製造中進行的流程改進，首先，我們確實看到了商品成本的改善，正如我們很早就與 Rybelsus 討論的那樣。此外，我們還在做的是，我們正在研究 50 毫克版本的片劑配方，從而也在改善我們產品的毛利率方面尋找某些機會。總而言之，如果我們進入市場，我們預計會看到一款具有吸引力的產品，而且其毛利率水平也會如此。

Thank you, Karsten. And Martin, combined answer to make it sound like 1 answer to the second question on semi HFpEF and Mim8.

謝謝你，卡斯滕。Martin，結合答案使其聽起來像是關於 semi HFpEF 和 Mim8 的第二個問題的 1 個答案。

That's going to be a tall order, combining obesity and hemophilia, but I'm going to give it a try. On HFpEF, we see obviously a great number of patients suffering from heart failure, and there's no treatment specifically for HFpEF out there. These patients have a severe impact on their everyday life: on their function, on their quality of life and obviously on their outcomes. And we have indications that semaglutide may be an impactful treatment in this space, specifically because 80% of people with HFpEF suffer from obesity. And we have clear indications that weight loss will improve the outlook, the quality of life and the activity of daily living with these patients. So we see this as an opportunity to serve some patients with currently no treatment and a potential for a label expansion of the obesity label for semaglutide.

考慮到肥胖和血友病，這將是一項艱鉅的任務，但我會嘗試一下。關於 HFpEF，我們顯然看到大量患者患有心力衰竭，並且沒有專門針對 HFpEF 的治療方法。這些患者對他們的日常生活產生嚴重影響：他們的功能、生活質量以及明顯的結果。我們有跡象表明，索馬魯肽可能是該領域的一種有效治療方法，特別是因為 80% 的 HFpEF 患者患有肥胖症。我們有明確的跡象表明，減肥將改善這些患者的前景、生活質量和日常生活活動。因此，我們認為這是一個為一些目前尚未接受治療的患者提供服務的機會，並且有可能擴大索馬魯肽的肥胖標籤。

Moving fastly then to the Mim8 question, we will see a readout from different cohorts throughout the next 3 quarters. We will combine our assessment of those readouts and report on the efficacy and safety of Mim8 later this year, as based on these data.

然後快速轉向 Mim8 問題，我們將在接下來的 3 個季度看到來自不同群體的讀數。我們將結合對這些讀數的評估，並根據這些數據在今年晚些時候報告 Mim8 的功效和安全性。

Thank you, Martin. So really no change to Mim8 compared to previous quarters' comments.

謝謝你，馬丁。因此，與前幾個季度的評論相比，Mim8 確實沒有變化。

Our next question comes from Sachin Jain from Bank of America.

我們的下一個問題來自美國銀行的 Sachin Jain。

Thanks for taking my questions. I've got a 2-parter on obesity, if I may. I understand your midterm excitement build in the market, but I wonder if you could indulge and just give some color on launch expectations. I'm going to frame the question versus consensus. So consensus has sema launching 50% faster than the initial Saxenda launch, layering on top of Saxenda for (technical difficulty) flat. So (technical difficulty) perspectives on the speed of sema launch versus prior Saxenda? What factors should we be thinking about as we think about this launch versus prior in terms of pricing, payer familiarity, where education is?

感謝您回答我的問題。如果可以的話，我有一個關於肥胖問題的二人伴侶。我理解您對市場的中期興奮情緒，但我想知道您是否可以放縱一下，並就發布預期給出一些顏色。我將闡述問題與共識的關係。因此，共識認為 sema 的啟動速度比最初的 Saxenda 啟動速度快 50%，在 Saxenda 之上分層（技術難度）持平。那麼（技術難度）sema 與之前的 Saxenda 的發布速度有何不同？當我們考慮此次推出與之前的定價、付款人熟悉程度、教育領域等方面相比時，我們應該考慮哪些因素？

And then the second is how to think about the 2 products in combination; what short-term dynamics should we be thinking of in terms of potential sema cannibalization of Saxenda patients? I understand your state on dynamic debate, but I expect takes time to manifests in terms of patient build.

第二個是如何考慮這兩種產品的組合；就 Saxenda 患者潛在的 sema 蠶食而言，我們應該考慮哪些短期動態？我理解您在動態辯論中的狀態，但我預計需要時間才能在患者建立方面體現出來。

Thank you, Sachin Jain. While we do not kind of guide on launch trajectory, et cetera, for products or comment on consensus estimates, Camilla, what can we say on this?

謝謝你，薩欽·賈恩。雖然我們沒有對產品的發布軌蹟等提供指導，也沒有對共識估計發表評論，卡米拉，對此我們能說些什麼呢？

Yes. So what we are trying to do in many countries, but also of course in the U.S., is to build the market, as you rightly said. And with the launch of semaglutide 2.4 with a much higher efficacy, we know from our early discussions with payers in general, that weight loss in the magnitude of what we are seeing with 2.4 is of course of high relevance. So it will feed into our attempts to build the market in terms of making sure that more patients seek treatment for obesity care because obesity care has such a -- obesity has such a big influence on the health care system and the cost.

是的。因此，正如您所說，我們在許多國家（當然也在美國）正在努力建立市場。隨著功效更高的索馬魯肽 2.4 的推出，我們從與付款人的早期討論中得知，我們所看到的 2.4 的減肥幅度當然具有高度相關性。因此，它將有助於我們建立市場的努力，以確保更多的患者尋求肥胖症護理的治療，因為肥胖症護理對醫療保健系統和成本有很大的影響。

So of course, with higher efficacy, we are more likely to see a strong uptake of 2.4. But that is, of course, early days to say, but we are basing this just on efficacy. But we're also launching into a market that is more mature than what it was when we launched Saxenda. So in the meantime, of course, we have built the awareness around obesity. We're working to have it recognized as a disease in many countries around the world. We have launched new websites, Truth About Weight, for patients where they can learn about obesity and also rethink obesity for physicians, where they can also obtain more information about obesity in general. So a bigger sort of base to build on for a more effective product. So that's basically the difference in the situation compared to Saxenda, where we started very much from scratch.

當然，隨著功效的提高，我們更有可能看到 2.4 的強勁採用。當然，這還為時尚早，但我們只是根據功效來判斷。但我們也正在進入一個比我們推出 Saxenda 時更加成熟的市場。當然，與此同時，我們也建立了對肥胖的認識。我們正在努力讓世界上許多國家將其視為一種疾病。我們推出了新網站“體重的真相”，患者可以在其中了解肥胖症，也可以為醫生重新思考肥胖症，他們還可以獲得有關肥胖症的更多信息。因此，為更有效的產品奠定了更大的基礎。這基本上就是與 Saxenda 相比情況的不同，在 Saxenda，我們是從頭開始的。

In terms of cannibalization, it's difficult for us to comment on, and we cannot give details on that. But of course, we are launching a product that has more than twice the efficacy into the market.

關於蠶食，我們很難評論，也無法透露細節。當然，我們正在向市場推出一種功效兩倍以上的產品。

Yes. Thank you, Camilla. So it's, of course, still early days, but looking at the reports that come out from the medical community observing, say, the early payer dialogue, I think this is a significant different trajectory than what we have seen in the past. And I think, in my view, this is the first time there's a real solution to managing obesity with medical intervention. So I think it's really, really exciting.

是的。謝謝你，卡米拉。當然，現在還處於早期階段，但看看醫學界觀察到的報告，例如早期付款人對話，我認為這與我們過去看到的軌蹟有很大不同。我認為，在我看來，這是第一次通過醫療干預來真正解決肥胖問題。所以我認為這真的非常非常令人興奮。

Our next question comes from Michael Novod from Nordea.

我們的下一個問題來自 Nordea 的 Michael Novod。

It's Michael from Nordea. Two questions also. Maybe you could elaborate a bit on the sales differences between Q4 and Q1 in terms of Rybelsus in the U.S., which, of course, looks quite dramatic. I know you've been talking to the general volatility between quarters, but this looks very dramatic, so it would be great to get an update on that in more detail.

我是來自 Nordea 的邁克爾。還有兩個問題。也許您可以詳細說明一下 Rybelsus 在美國的第四季度和第一季度的銷售差異，當然，這看起來相當引人注目。我知道您一直在談論季度之間的總體波動性，但這看起來非常引人注目，因此如果能夠更詳細地了解最新情況，那就太好了。

And then secondly, on the 2.0 milligram refuse to file letter from the FDA in diabetes, and what kind of feedback you're getting on the 2.4 milligram sema obesity file? And also whether we should see a potential risk on sort of any type of read across between the 2 on the manufacturing side?

其次，關於 2.0 毫克拒絕提交 FDA 糖尿病相關信函，以及您在 2.4 毫克 sema 肥胖檔案中得到了什麼樣的反饋？此外，我們是否應該看到製造方面兩者之間任何類型的讀取都存在潛在風險？

Thank you, Michael. First, Karsten, on Rybelsus sales Q4 last year versus Q1 this year.

謝謝你，邁克爾。首先，Karsten 介紹了去年第四季度和今年第一季度的 Rybelsus 銷量。

Absolutely. And I recognize that it looks odd that actually Rybelsus sales being a launch product is lower in Q1 this year compared to Q4 last year. I would say there are a couple of technicalities that explains basically all of it. And then I think we should talk to the underlying kind of dynamics of the products, which are 100% intact.

絕對地。我認識到，實際上 Rybelsus 作為一款推出產品，今年第一季度的銷量低於去年第四季度，這看起來很奇怪。我想說有一些技術細節基本上可以解釋所有這些。然後我認為我們應該談談產品的潛在動態，它們是 100% 完好無損的。

So on the technicalities, so let me just start out by 2 pieces. First of all, looking at quarterly sales on a launched product is always super dangerous. And we've seen that again and again for different dynamics. The 2 key dynamics you should take into account here is, first of all, that's a so-called [ex-factory] ratio. So basically, the ratio between what we sell to wholesalers and scripts being written to patients. And there's quite some volatility on launch products in that ratio since that -- we are building pipeline in the supply chain when you're launching a product. So basically, product going into rural pharmacies and distribution centers across a nation. So we saw that in the fourth quarter of last year, that there's quite a high [ex-factory] ratio and where we see a more normal [ex-factory] ratio in the first quarter of this year. So that would be kind of a natural launch supply chain volatility.

關於技術細節，讓我從 2 件開始。首先，查看已推出產品的季度銷售額總是非常危險的。我們已經在不同的動態中一次又一次地看到這一點。您在這裡應該考慮的兩個關鍵動態是，首先，這是所謂的[出廠]比率。所以基本上，我們賣給批發商的產品和寫給患者的腳本之間的比率。從那時起，推出產品的比例就有相當大的波動——當你推出產品時，我們正在供應鏈中建立管道。基本上，產品進入全國各地的農村藥房和配送中心。所以我們看到去年第四季度的[出廠]比率相當高，而今年第一季度我們看到比較正常的[出廠]比率。因此，這將是一種自然的供應鏈波動。

And then the second piece to take into account is on adjustments to rebates as we've also seen on launched products. So being a launched product, you don't know exactly how much is being utilized through cash programs and co-pay and different insurances. And there, of course, with the lag we have, there will be some adjustments over time. And that was what we talked to in Q4, that we had a favorable impact to our GLP-1 business. And I would say for Rybelsus, it's in isolation. We didn't call it out on the brand. It's less than DKK 100 million in the fourth quarter. But of course, for a launch brand with somewhat limited sales, then, of course, it's a bigger piece. So [ex-factory] ratio and changes to rebates and estimates in the fourth quarter. Adjusting for that, 20% volume increase from the fourth quarter to the first quarter. But Camilla, on the underlying fundamentals on Rybelsus?

然後要考慮的第二個因素是回扣的調整，正如我們在已推出的產品上看到的那樣。因此，作為一款已推出的產品，您無法確切知道通過現金計劃、共付額和不同的保險使用了多少資金。當然，由於我們存在滯後，隨著時間的推移，將會有一些調整。這就是我們在第四季度談到的，我們對 GLP-1 業務產生了有利的影響。我想說，對於 Rybelsus，它是孤立的。我們沒有在品牌上大聲疾呼。第四季度不到 1 億丹麥克朗。但當然，對於銷量有限的推出品牌來說，這當然是一個更大的部分。因此，[出廠]比率以及第四季度回扣和估計的變化。對此進行調整後，第四季度的銷量比第一季度增長了 20%。但是卡米拉，關於 Rybelsus 的基本面呢？

Yes. On the underlying fundamentals, we track on a number of parameters to understand, of course, our uptake and launch with Rybelsus. And all of that is in line with our ambition. So it means that the -- that means the number of prescribers is continuing to progressing well. And we also see that awareness and preference is improving over time. Especially on the preference to prescribe Rybelsus, that has increased significantly and looks very strong also compared to other branded OADs in the market. So what we are working on right now is to increase our awareness of the brand, and that comes with us and the reps coming back into the market and as we continue the launch trajectory. So we are quite confident with that path.

是的。在基本原理上，我們跟踪了許多參數，以了解我們對 Rybelsus 的採用和推出。所有這一切都符合我們的抱負。所以這意味著——這意味著處方醫生的數量繼續保持良好進展。我們還看到，隨著時間的推移，人們的意識和偏好正在不斷提高。尤其是對處方 Rybelsus 的偏好顯著增加，與市場上其他品牌的 OAD 相比，這種偏好也顯得非常強勁。因此，我們現在正在努力提高我們對品牌的認知度，這伴隨著我們和銷售代表重返市場以及我們繼續推出的軌跡而來。所以我們對這條道路非常有信心。

We also continue to see that the source of business and the positioning is working out so that the sourcing is 80% outside the GLP-1 class, as we have talked to before also. So it means that we continue to be very confident in Rybelsus and the commercial strategy. But of course, we also see that it's a very promotion sensitive launch product, and we have -- and as we talked to before, whenever we have reintroduced the product, we see that we get back on a very strong trajectory. We continue to support Rybelsus, of course, also with DTC. And of course, also with reps more and more in the field, as we just talked about before.

我們還繼續看到業務來源和定位正在製定，因此 80% 的採購都在 GLP-1 類別之外，正如我們之前討論過的那樣。所以這意味著我們仍然對 Rybelsus 和商業策略非常有信心。但當然，我們也看到這是一個對促銷非常敏感的發布產品，而且正如我們之前所說，每當我們重新推出該產品時，我們都會看到我們回到了非常強勁的軌道。當然，我們會繼續支持 Rybelsus，當然也包括 DTC。當然，正如我們之前談到的，現場的代表也越來越多。

Thank you, Karsten, Camilla. Strong confidence from our side in the launch trajectory for Rybelsus. And with that, over to Martin on read across from the refusal to file letter from the FDA to 2.4 milligram.

謝謝你，卡斯滕，卡米拉。我們對 Rybelsus 的發射軌跡充滿信心。接下來，請馬丁閱讀 FDA 拒絕提交 2.4 毫克的信件。

Yes. Thank you very much. So broadly speaking, I don't think I will speculate on an ongoing regulatory review. But maybe just say that the FDA has accepted the submission of the 2.4 milligram. It's under review, and we currently have no indications of that file being impacted by the refusal to file on the Ozempic 2.0 milligram.

是的。非常感謝。從廣義上講，我認為我不會猜測正在進行的監管審查。但也許只是說 FDA 已經接受了 2.4 毫克的提交。該文件正在接受審查，目前沒有跡象表明該文件受到拒絕提交 Ozempic 2.0 毫克的影響。

The next question comes from Michael Leuchten from UBS.

下一個問題來自瑞銀集團的 Michael Leuchten。

It's Michael Leuchten from UBS. Just 2 quick ones, please. Just in terms of the mix -- price/mix effect on the insulin side, there seems to be quite a few things going on in the U.S. at the moment, with patient access coming out, [340Bs] playing a part. As we think about this beyond 2021, would you be able to give a bit of a feel for what the underlying conventional price/mix effect is? And what is sort of 2021 specific?

我是瑞銀集團 (UBS) 的邁克爾·洛希滕 (Michael Leuchten)。請快一點。就胰島素方面的混合而言——價格/混合效應，目前美國似乎發生了很多事情，隨著患者訪問的出現，[340Bs]發揮了作用。當我們在 2021 年之後思考這一問題時，您能否對潛在的傳統價格/組合效應有一些了解？2021 年具體是什麼？

And then the second question, just going back to the tax question. It doesn't look like there will be any manufacturing offset in terms of tax rebates in the U.S. Does that have any relevance in terms of how you think about your manufacturing setup as you increase your oral manufacturing platform?

然後是第二個問題，回到稅收問題。美國的退稅似乎不會有任何製造抵消。這與您在增加口腔製造平台時如何看待製造設置有任何相關性嗎？

Thank you, Michael. Two questions for you, Karsten, on price/mix effect on insulin and also looking a bit into the future. And then, again, on taxes in the U.S., combined with manufacturing footprint in the U.S.

謝謝你，邁克爾。卡斯滕，有兩個問題要問您，關於價格/混合對胰島素的影響，以及對未來的展望。然後，再一次，關於美國的稅收，以及美國的製造業足跡。

Yes. Thank you for those questions, Michael. So first of all, all on insulin and insulin dynamics, you see our North American business being down 10% in the first quarter on insulin. Which is a function of both lower volumes. It's enhanced rebates and then an offset from positive channel mix. So what you should expect going forward is that, of course, there will be competition in the market for volumes with potentially more biosimilars entering into the market. So that will intensify. But of course, we'll be defending our leading position in the market in terms of market share. With competition comes also pressure on rebating and pricing. So the dynamic around pricing and rebating, we do expect to continue for those reasons.

是的。謝謝你提出這些問題，邁克爾。首先，就胰島素和胰島素動態而言，我們的北美業務在第一季度因胰島素下降了 10%。這是兩個較低體積的函數。它是增強的回扣，然後抵消積極的渠道組合。因此，您應該期待的是，當然，市場上將會存在數量競爭，可能會有更多的生物仿製藥進入市場。所以這種情況將會加劇。但當然，我們將捍衛我們在市場份額方面的市場領先地位。隨著競爭的到來，折扣和定價也面臨壓力。因此，出於這些原因，我們確實預計圍繞定價和折扣的動態將會持續下去。

And as to channel mix, the positive factor on channel mix is mainly related to 340B, where we are basically -- we stopped our shipments as (technical difficulty) with the full year. We stopped our shipments to contract pharmacies, which enables us to avoid double dipping of rebates and hence, a better channel mix impact on our insulin sales. That is, of course, only something one can do one time. I would have to say that on 340B, while comfortable in terms of what we included in the first quarter, of course, there's still some uncertainty vis-à-vis legal cases and legislative impacts around future rule-making on a prospective basis.

至於渠道組合，渠道組合的積極因素主要與 340B 有關，我們基本上 - 由於全年（技術困難）而停止了發貨。我們停止向合同藥店發貨，這使我們能夠避免回扣的雙重下降，從而對我們的胰島素銷售產生更好的渠道組合影響。當然，這是一件只能做一次的事情。我不得不說，關於 340B，雖然我們對第一季度的內容感到滿意，但在未來的基礎上，法律案件和未來規則制定的立法影響仍然存在一些不確定性。

Then to your question on taxes and manufacturing offsets, then I would say the starting point, when we look at our manufacturing footprint is that we look at the supply chain backup and redundancies and closeness to markets. So of course, we take taxes into account, but tax is not a prime criteria for when we decide where to put our manufacturing footprint. So what we're looking at now is that we're just in our final stages of finalizing documentation on our U.S. API expansion project. So project running according to plan. So we -- now we're moving into a ramp-up phase. And the CapEx ramp up we've been signaling with now DKK 7.5 billion CapEx spend this year, is mainly driven by expansions in Denmark. So I'd say no implications for our CapEx manufacturing strategy from the changes in U.S. tax legislation.

然後，對於您關於稅收和製造業抵消的問題，我想說，當我們審視我們的製造業足跡時，我們的出發點是我們關注供應鏈備份、裁員以及與市場的緊密程度。因此，我們當然會考慮稅收，但稅收並不是我們決定將製造足跡放在哪裡的主要標準。因此，我們現在關注的是，我們正處於美國 API 擴展項目文檔最終確定的最後階段。所以項目按計劃進行。所以我們現在正在進入一個加速階段。我們一直在暗示今年資本支出將增加 75 億丹麥克朗，這主要是由丹麥的擴張推動的。因此，我認為美國稅收立法的變化不會對我們的資本支出製造戰略產生任何影響。

Thank you, Karsten. And then we have time for a last set of questions, please.

謝謝你，卡斯滕。然後我們有時間回答最後一組問題。

Our next question comes from Carsten Madsen from SEB.

我們的下一個問題來自 SEB 的 Carsten Madsen。

Maybe I'll actually only take 1 question here for Martin. It's in relation to the NASH Phase III trial with sema. You mentioned that there are 2 binary histology endpoints. What does this actually mean? In Phase II, you showed the resolution of NASH. But with no worsening of fibrosis, do you now also need to show an improvement in fibrosis and not only no worsening of fibrosis?

也許我實際上只會問馬丁一個問題。它與 sema 的 NASH III 期試驗有關。您提到有 2 個二元組織學終點。這實際上意味著什麼？在第二階段，您展示了 NASH 的解決方案。但是，在纖維化沒有惡化的情況下，您現在是否還需要證明纖維化有所改善，而不僅僅是纖維化沒有惡化？

Thank you, Carsten. Over to you, Martin.

謝謝你，卡斯滕。交給你了，馬丁。

Yes. It's a super relevant question. And the regulatory guidance basically stipulates that you have to win on 2 counts. You had to show improvement in steatohepatitis. and you had to show improvement in fibrosis. Just to clarify, of course, being a Phase II trial, this trial was not powered to look at fibrosis. However, numerically, we did see an improvement in fibrosis as well as the sort of stopping in worsening of fibrosis. If we see the same numerical change in the Phase III trial, we will actually be in a place where we are not only clinically relevant but also statistically significant and thereby living up to the regulatory guidance. So what we need is for our Phase III trial to confirm what we saw in Phase II.

是的。這是一個非常相關的問題。監管指南基本上規定你必須在兩個方面獲勝。您必須證明脂肪性肝炎有所改善。並且你必須表現出纖維化的改善。當然，為了澄清這一點，作為一項 II 期試驗，該試驗並不能研究纖維化。然而，從數字上看，我們確實看到了纖維化的改善以及纖維化惡化的停止。如果我們在 III 期試驗中看到相同的數字變化，我們實際上將處於這樣一個位置：我們不僅具有臨床相關性，而且具有統計顯著性，從而符合監管指導。因此，我們需要的是第三階段試驗來確認我們在第二階段所看到的結果。

And then (multiple speakers)

然後（多位發言者）

The second question?

第二個問題？

Yes. I had a second question that was just for the other Karsten. In terms of the gross margin development, 80 bps of the 130 bps lower gross margin this quarter versus last year's FX, how is the remaining 50 bps divided between amortizations and price pressure on your price mix, you can say?

是的。我還有第二個問題是針對另一個卡斯滕的。就毛利率發展而言，本季度毛利率比去年外匯毛利率低 130 個基點，其中 80 個基點是如何在攤銷和價格組合的價格壓力之間分配的，您可以說嗎？

Yes. So that's what is for other Karsten. And I think when -- what we disclosed upon acquiring Emisphere was that we do expect a negative impact here in the first year of less than 1% of OP simply due to the delta between the royalty payments under the previous contract and then the amortization profile, having acquired the company. So if you take that 1% or less than 1%, then that will make you into -- that corresponds to less than 50 bps on the margin.

是的。這就是其他卡斯滕的情況。我認為，我們在收購 Emisphere 時披露的是，我們確實預計第一年的負面影響將低於 OP 的 1%，這僅僅是由於先前合同下的特許權使用費支付與攤銷概況之間的差額，收購了該公司。因此，如果你採用 1% 或低於 1%，那麼這將使你陷入——相當於邊際幅度低於 50 個基點。

So the main driver is in reality amortization related to Emisphere. You can look in the cash flow statement on the step-up in depreciation and amortizations also, just to get a feel for it. But that's the main driver. The other effects remains the same. We continue to drive productivity. We continue to get the product mix gain from GLP-1, and we continue to see some negative impact from prices in the U.S.

因此，主要驅動力實際上是與 Emisphere 相關的攤銷。您還可以在現金流量表中查看折舊和攤銷的增加，只是為了感受一下。但這是主要驅動力。其他效果保持不變。我們繼續提高生產力。我們繼續從 GLP-1 中獲得產品組合收益，並且我們繼續看到美國價格帶來的一些負面影響。

Thank you, Carsten, and thank you, Karsten. With that, we thank you for the attention today at our conference call. And if you have more questions, feel free to contact our Investor Relations officers. And with that, we wish you a good day. Thank you. Bye-bye.

謝謝你，卡斯滕，謝謝你，卡斯滕。在此，我們感謝您今天對我們的電話會議的關注。如果您有更多問題，請隨時聯繫我們的投資者關係官員。在此，我們祝您有美好的一天。謝謝。再見。

Thank you. This now concludes our conference call. Thank you all for attending. You may now disconnect your lines.

謝謝。我們的電話會議到此結束。感謝大家的出席。您現在可以斷開線路。