諾和諾德 (NVO) 2021 Q4 法說會逐字稿

Hello, everyone, and welcome to the Q4 2021 Novo Nordisk A/S Earnings Presentation. (Operator Instructions)

大家好，歡迎來到 2021 年第四季度 Novo Nordisk A/S 收益報告。 （操作員說明）

Today, I'm pleased to present Lars Fruergaard Jorgensen. Please go ahead with your meeting.

今天，我很高興介紹 Lars Fruergaard Jorgensen。請繼續你的會議。

Thank you very much. And let me start by thanking Bank of America and Sachin Jain for hosting us today. First slide is our forward-looking statements. So I remind you that we'll be talking about the future, and it might turn out to be different than what we preach.

非常感謝你。首先讓我感謝美國銀行和 Sachin Jain 今天接待我們。第一張幻燈片是我們的前瞻性陳述。所以我提醒你，我們將談論未來，結果可能與我們所宣揚的不同。

Looking at the highlights for the full year of 2021. We are very pleased with how we have executed on all 4 quadrants of our strategic aspirations. We'll cover most of it today. But just on this slide, we mentioned that on ESG, we're very pleased in how we are living up to both our social and environmental responsibilities, making good progress there. And the other quadrants, you will hear about as we present.

回顧 2021 年全年的亮點。我們對我們在戰略目標的所有 4 個像限上的執行情況感到非常滿意。我們今天將介紹大部分內容。但就在這張幻燈片上，我們提到在 ESG 方面，我們很高興我們如何履行我們的社會和環境責任，並在這方面取得了良好的進展。其他像限，你會在我們介紹的時候聽到。

So if you go to the next slide, this is an overview of our sales growth of 14% in 2021. Very strong growth. We see that both international operations and now also North America operations is a nice double-digit growth territory, both growing by 14%. And when you break it down to geographies, you see nice double-digit growth coming from all geographies.

因此，如果您轉到下一張幻燈片，這是對我們 2021 年銷售額增長 14% 的概述。非常強勁的增長。我們看到，國際業務和現在的北美業務都是一個不錯的兩位數增長領域，均增長了 14%。當你把它分解到各個地區時，你會看到來自所有地區的兩位數增長。

The growth is supported by all therapy areas, obviously driven by strong momentum in the GLP-1-based franchises, diabetes and obesity, but also continued growth contribution from our Biopharm franchise.

這一增長受到所有治療領域的支持，顯然是由基於 GLP-1 的特許經營權、糖尿病和肥胖症的強勁勢頭推動的，而且我們的 Biopharm 特許經營權的持續增長貢獻。

If you go to the next slide, here's an overview of the Wegovy situation. You all know that we, unfortunately, late December had to announce a stop of supply from a contract manufacturer helping us with the filling of Wegovy. We do all API in-house, but we depend to a large degree on external filling, and this supplier had to take down manufacturing because of a GMP issue. We guided that we expected initially to be able to fulfill approximately 60% to 90% of, say, end of year business volume. We have improved that situation since then. And now we expect to be able to match what we were selling at the end of the year. And we're still on track to resuming full supply of the U.S. demand when we get to the second half year. So somewhat a better outlook for Wegovy supplies than we perhaps feared at the end of 2021.

如果您轉到下一張幻燈片，這裡是 Wegovy 情況的概述。你們都知道，不幸的是，我們在 12 月下旬不得不宣布一家合同製造商停止供應，幫助我們填充 Wegovy。我們在內部完成所有 API，但我們在很大程度上依賴於外部灌裝，並且由於 GMP 問題，該供應商不得不停止生產。我們指導我們最初預計能夠完成大約 60% 到 90% 的業務量，例如年終業務量。從那時起，我們已經改善了這種情況。現在我們希望能夠與我們在年底銷售的產品相匹配。到下半年，我們仍有望恢復對美國需求的全部供應。因此，Wegovy 供應的前景比我們在 2021 年底可能擔心的要好一些。

With that, I'll hand over to Camilla for an update on commercial.

有了這個，我將移交給卡米拉以獲取有關廣告的更新。

Yes. Thanks a lot, Lars. So in obesity, our sales grew by 55% last year, split with a 57% increase in North America and 52% increase in IO. We are now in the U.S. at 22,000 weekly scripts for Wegovy and more than 70% of those are coming from people who are new to the anti-obesity medication class. Despite the fact that we've now put our sales and marketing activities on hold until there is sufficient supply, then our commitment to obesity remains very strong and is unchanged.

是的。非常感謝，拉斯。因此，在肥胖方面，我們去年的銷售額增長了 55%，其中北美增長了 57%，IO 增長了 52%。我們現在在美國每週為 Wegovy 提供 22,000 個腳本，其中超過 70% 來自抗肥胖藥物課程的新手。儘管我們現在暫停銷售和營銷活動，直到有足夠的供應，但我們對肥胖的承諾仍然非常堅定並且沒有改變。

On the next slide, you see the overall U.S. GLP-1 diabetes segment. And here you see our market growth around 30% driven by once weekly GLP-1. You also see our NBRx leadership now 63.9% and Ozempic remains the NBRx market share leader within the injectable GLP-1 segment. And overall, our market leadership is now above 50% market share.

在下一張幻燈片中，您可以看到美國 GLP-1 糖尿病的整體情況。在這裡，您可以看到我們的市場增長約 30%，這是由每週一次的 GLP-1 推動的。您還可以看到我們的 NBRx 領導地位現在達到 63.9%，Ozempic 仍然是可注射 GLP-1 細分市場中 NBRx 市場份額的領導者。總體而言，我們的市場領導地位現已超過 50% 的市場份額。

And with that, we'll move on to Martin.

有了這個，我們將繼續討論馬丁。

Yes, thanks very much, Camilla. As you know, we have initiated Phase III programs across all of our therapy areas. So while this slide is a little bit busy, it's actually only reflecting some of our R&D milestones, both obviously covering Q4 of '21 and going through '22.

是的，非常感謝，卡米拉。如您所知，我們已經在我們所有的治療領域啟動了 III 期計劃。因此，雖然這張幻燈片有點忙，但它實際上只反映了我們的一些研發里程碑，顯然都涵蓋了 21 年第四季度和 22 年。

In the diabetes space, obviously, we were super happy to receive both the Ozempic 2.0 milligram positive opinion from CHMP in Q4 '21 and the approval also in Europe in January of '22. And we're looking forward to a U.S. decision also on Ozempic 2.0 milligram later this year.

顯然，在糖尿病領域，我們非常高興在 21 年第四季度收到 CHMP 的 Ozempic 2.0 毫克積極意見，並在 22 年 1 月在歐洲獲得批准。我們期待今年晚些時候美國也對 Ozempic 2.0 毫克做出決定。

As you know, we are investigating the impact of icosema in type 2 diabetes, and we are expecting Phase II results of this, allowing us to make a Phase III stop-go (sic) [go, no-go] decision in second half of this year.

如您所知，我們正在調查 2 型糖尿病中 icosema 的影響，我們期待這方面的 II 期結果，使我們能夠在下半年做出 III 期停走（原文如此）[go, no-go] 的決定今年的。

Also, I want to call out that we, in Q4 of last year, initiated the Phase III program for icosema, which is the combination of once weekly icodec and once weekly semaglutide allowing again for the true combination accruing the efficacy benefits and the downsizing of tolerability issues in that combination but also a convenience benefit in terms of this is an asset that can potentially replace basal bolus insulin therapy. And therefore, allowing patients going from 28 weekly injections to as little as 1 weekly injection. Obviously, a very attractive offering in that space.

另外，我想指出，我們在去年第四季度啟動了 icosema 的 III 期計劃，這是每週一次的艾科德和每週一次的索馬魯肽的組合，再次實現了真正的組合，從而產生了療效益處和縮小了該組合中的耐受性問題以及就此而言的便利性益處是可以潛在地替代基礎推注胰島素治療的資產。因此，允許患者從每週 28 次注射減少到每週 1 次注射。顯然，這是該領域非常有吸引力的產品。

Then '22 is going to be very, very exciting in that we have 6 icodec Phase III studies basically our entire Phase III program reading out during the course of '22 in both first and second half, allowing us to aim for a regulatory submission very early in '23.

然後 '22 將非常非常令人興奮，因為我們有 6 項 icodec III 期研究，基本上我們的整個 III 期計劃在 '22 的上半年和下半年都在宣讀，這使我們能夠非常瞄準監管提交23 年初。

In obesity, as you know, we received a positive opinion on Wegovy. You've also heard us announce that for allowing ourselves to prioritize Wegovy supply in the U.S., we will now initiate icosema Phase III for obesity in second half of this year.

如您所知，在肥胖方面，我們收到了對 Wegovy 的積極評價。您還聽說我們宣布，為了讓自己優先考慮在美國供應 Wegovy，我們現在將在今年下半年啟動針對肥胖症的icosema III 期。

Biopharma has been very, very exciting, both in the last quarter of '21, but also it is going to be -- continue to be exciting in '22. We've seen the very positive and very robust Phase III data coming out of Sogroya, our once weekly growth hormone therapy. We've seen the initial cohorts reading out on Mim8, our very aspirational hemophilia asset. These data allowed us to initiate Phase III already in Q4 of last year, initiate in the sense that we are running patients in and observing them, and we intend to initiate Phase III treatment with Mim8 in second half of this year following the readout of the full data set of Phase I and II.

生物製藥一直非常非常令人興奮，無論是在 21 年的最後一個季度，而且它將在 22 年繼續令人興奮。我們已經看到來自我們每週一次的生長激素療法 Sogroya 的非常積極和非常穩健的 III 期數據。我們已經在 Mim8 上看到了最初的隊列，這是我們非常有抱負的血友病資產。這些數據使我們能夠在去年第四季度啟動 III 期，在我們正在運行患者並觀察他們的意義上啟動，並且我們打算在今年下半年開始使用 Mim8 進行 III 期治療。第一階段和第二階段的完整數據集。

And finally, and also very exciting, we'll see the Phase III concizumab results also in hemophilia and aiming for a U.S. and Japan submission during second half of this year.

最後，也是非常令人興奮的，我們將看到 concizumab 在血友病方面的 III 期結果，併計劃在今年下半年向美國和日本提交。

And with that, over to you, Karsten.

有了這個，交給你，卡斯滕。

Thank you, Martin. Looking at our P&L for 2021. The results really marked a step up in growth compared to what we've seen in the last few years. So delivering on our accelerated sales aspirations. So underlying double-digit growth at 14% in a historic context, 14% is the strongest growth rate we've seen for the company since 2006. And in absolute terms, the step-up is between -- from 2022 in absolute DKK is to the tune of 2x compared to the biggest step-up we've seen historically.

謝謝你，馬丁。看看我們 2021 年的損益表。與過去幾年的情況相比，結果確實標誌著增長的進步。因此，實現我們加速銷售的願望。因此，在歷史背景下以 14% 的潛在兩位數增長，14% 是我們自 2006 年以來我們所看到的公司最強勁的增長率。從絕對值來看，增幅介於 - 從 2022 年開始，絕對丹麥克朗是與我們歷史上看到的最大提升相比，達到了 2 倍。

That, of course, is enabled through continued investments in our commercial franchise. So we have sales and distribution costs increasing by 15% at constant exchange rates. And furthermore, we're continuing to invest in our future growth platforms and technologies as Martin was just covering before, and our R&D costs increasing by 16%. We continue to drive efficiencies in our back office cost and hence, a lower growth rate there.

當然，這是通過對我們的商業特許經營權的持續投資來實現的。因此，按固定匯率計算，我們的銷售和分銷成本增加了 15%。此外，我們將繼續投資於我們未來的增長平台和技術，就像 Martin 之前剛剛介紹的那樣，我們的研發成本增加了 16%。我們繼續提高後台辦公成本的效率，因此那裡的增長率較低。

Net-net, operating profit increase of 13% at constant exchange rates. Then some financial items related to hedging and a tax rate of 19.2%, impacted by some one-offs related to our BD/M&A transactions that we entertained during 2020 and 2021. And as a consequence, a net profit increase of 13% and diluted earnings per share up by 15% to DKK 20.74.

按固定匯率計算，淨營業利潤增長 13%。然後是一些與對沖相關的金融項目和 19.2% 的稅率，受我們在 2020 年和 2021 年期間接受的與我們的 BD/M&A 交易相關的一些一次性交易的影響。因此，淨利潤增長了 13% 並被稀釋每股收益增長 15% 至 20.74 丹麥克朗。

And in terms of allocation to our shareholders, then the DKK 20.74 per share we basically used to deploy a dividend for the 26th consecutive year. So the proposal at the AGM will be a full year dividend of DKK 6.90 on top of the DKK 3.50 we issued in August. So in total, DKK 10 for the year of 2021. And on top of that, the Board is proposing -- or have decided on a new share buyback program of DKK 22 billion, up from DKK 20 billion in 2021.

在分配給我們的股東方面，我們基本上連續第 26 年使用每股 20.74 丹麥克朗來分配股息。因此，股東周年大會上的提議將是在我們 8 月發行的 3.50 丹麥克朗的基礎上，全年派發 6.90 丹麥克朗的股息。因此，總體而言，2021 年為 10 丹麥克朗。除此之外，董事會正在提議或已決定一項 220 億丹麥克朗的新股票回購計劃，高於 2021 年的 200 億丹麥克朗。

Talking about 2022 outlook is a continuation of the solid growth we saw in '21. We do have a negative impact from VBP in China and having 340B benefits in the U.S. in our base. And as a consequence, we are guiding for a sales growth of 6% to 10% at constant exchange rates for the year.

談論 2022 年的前景是我們在 21 年看到的穩健增長的延續。我們確實受到了中國 VBP 的負面影響，並且在我們的基地擁有美國的 340B 福利。因此，我們指導全年以固定匯率計算銷售額增長 6% 至 10%。

Operating profit growth of 4% to 8% being impacted by the Dicerna acquisition, which closed on December 28 of last year. Currencies are very favorable in '22, mainly linked to the U.S. dollar, which at the time we issued our guidance. We used a U.S. dollar rate of DKK 6 -- [DKK 6, DKK 7 and up] per U.S. dollar compared to an average in '21 of DKK 6.29. So that drives the positive currency impact of 5 percentage points on sales growth and 7% on operating profit growth. So basically, the U.S. dollar, Canadian dollar and CNY, the Chinese currency, are the main drivers of the positive currency impacts you're seeing here.

受去年 12 月 28 日結束的 Dicerna 收購影響，營業利潤增長 4% 至 8%。 22 年的貨幣非常有利，主要與美元掛鉤，當時我們發布了我們的指導。我們使用的美元匯率為每美元 6 丹麥克朗——[6 丹麥克朗、7 丹麥克朗及以上]，而 21 年的平均匯率為 6.29 丹麥克朗。因此，這推動了對銷售增長 5 個百分點和對營業利潤增長 7% 的積極貨幣影響。所以基本上，美元、加元和人民幣是您在這裡看到的積極貨幣影響的主要驅動因素。

Then we have 12 months on the U.S. dollar. And as a consequence, we have our hedging losses accounted on net financial items. And as a consequence, a loss to the tune of DKK 2.8 billion expected at the DKK 6.67 exchange rate kroner to U.S. dollar.

然後我們有 12 個月的美元匯率。因此，我們將對沖損失計入淨金融項目。因此，按 6.67 丹麥克朗兌美元匯率計算，預計將損失 28 億丹麥克朗。

Tax rate 2022, as in previous years, and the continuation of our discipline in converting our earnings to cash flow and the guidance, excluding any major BD activities, free cash flow guidance of between DKK 50 billion and DKK 55 billion.

與往年一樣，2022 年的稅率，以及我們在將收益轉化為現金流和指導（不包括任何主要的 BD 活動）方面的紀律的延續，自由現金流指導在 500 億丹麥克朗和 550 億丹麥克朗之間。

With that, back to you, Lars.

有了這個，回到你身邊，拉斯。

Thank you, Karsten. So we're excited about the momentum in our business coming out of 2021 and feel we are well on track to achieve our aspirations for 2025, looking at the build of our pipeline and also the coming readout for 2022. And we hope to see many of you at our Capital Markets Day on March 3 here in Copenhagen.

謝謝你，卡斯滕。因此，我們對 2021 年之後的業務發展勢頭感到興奮，並認為我們正在朝著實現 2025 年的目標邁進，著眼於我們的管道建設以及即將到來的 2022 年數據。我們希望看到更多3 月 3 日在哥本哈根舉行的資本市場日。

With that, I would like to close our presentation and open up for Q&A.

有了這個，我想結束我們的演示並開始問答。

(Operator Instructions) Our first question comes from Sachin Jain with Bank of America.

（操作員說明）我們的第一個問題來自美國銀行的 Sachin Jain。

So one on pipeline and then one on 483, if I may. So for Martin on pipeline, sema cagri Phase II data in diabetes is due second half of the year. Wondering if you can just provide a bit of background on target profile and what you've seen that gives you some confidence there. I'm specifically referring to any HbA1c blood glucose metrics you saw in the obesity data, which is a normal glycemic patients that gives you confidence. The reason for the question is I think there's always been greater excitement in obesity than diabetes. Just wondering whether that's shifting as we approach the Phase II data.

如果可以的話，一個在管道上，然後一個在 483 上。因此，對於管道中的 Martin 來說，糖尿病的 sema cagri II 期數據將在今年下半年發布。想知道您是否可以提供一些關於目標配置文件的背景以及您所看到的內容，這會給您帶來一些信心。我特別指的是你在肥胖數據中看到的任何 HbA1c 血糖指標，這是一個讓你有信心的正常血糖患者。這個問題的原因是我認為肥胖總是比糖尿病更令人興奮。只是想知道隨著我們接近第二階段的數據，這種情況是否會發生變化。

And then secondly, just on the FDA supply issue with Wegovy. Just a follow-up to my question on the call. So Henrik mentioned that supply should start at the CMO in the second quarter. I just wondered if you could clarify what steps remain between now and that supply restarting. I wonder if you could talk us through that. And I guess, I just wanted to get visibility, if you can, on one of the variables you've listed in December in time lines for sourcing of spare parts, and I guess potentially the [hepa filters]. So just wondering whether that's done and you're sort of getting close to completing production runs and sending validation data to the FDA.

其次，只是關於 Wegovy 的 FDA 供應問題。只是我在電話中提出的問題的後續行動。所以 Henrik 提到供應應該在第二季度從 CMO 開始。我只是想知道你是否可以澄清從現在到供應重啟之間還有哪些步驟。我想知道你能不能和我們談談。我想，如果可以的話，我只是想了解一下你在 12 月列出的備件採購時間線中的一個變量，我猜可能是 [hepa 過濾器]。所以只是想知道這是否已經完成，並且您即將完成生產運行並將驗證數據發送給 FDA。

Right. Thank you, Sachin. Martin, first, on icosema in diabetes.

對。謝謝你，薩欽。馬丁，首先，關於糖尿病中的積炭瘤。

Yes. Thanks a lot, Sachin. So first of all, I think it's important to call out that we've not seen any data on glycemic control with cagrilintide. As you obviously -- and you pointed that out yourself, we have data from obesity and obese patients. These are all normal glycemic and nondiabetic, and while we may see a hint towards impact on blood glucose, nothing that would substantiate us going into certainly Phase III.

是的。非常感謝，薩欽。所以首先，我認為重要的是要指出我們沒有看到任何關於卡格瑞肽控制血糖的數據。顯然，正如您自己指出的那樣，我們有來自肥胖和肥胖患者的數據。這些都是正常的血糖和非糖尿病，雖然我們可能會看到對血糖影響的暗示，但沒有任何證據可以證實我們肯定會進入第三階段。

That being said, as you obviously also know, an amylin analog is already on the market for the treatment of diabetes, pramlintide. While this is a short-acting analog, we do know that amylin has impact on gastric emptying. It does obviously had impact on body weight. It has impact on glucagon secretion. And therefore, we do believe that we need to investigate the potential impact of not cagrilintide in monotherapy but in combination with semaglutide to investigate that given that we don't have any clinical data Phase II, it seems to be the obvious place of doing that, allowing ourselves to initiate Phase III more or less at the same time as we aim to initiate the obesity trials, if that should pan out positive.

話雖如此，您顯然也知道，一種胰淀素類似物已經上市，用於治療糖尿病，普蘭林肽。雖然這是一種短效類似物，但我們確實知道胰淀素對胃排空有影響。它顯然對體重有影響。它對胰高血糖素的分泌有影響。因此，我們確實認為，我們需要調查不是卡格瑞肽單藥治療而是與索馬魯肽聯合使用的潛在影響，鑑於我們沒有任何 II 期臨床數據，這似乎是顯而易見的地方，允許我們在啟動肥胖試驗的同時或多或少地啟動第三階段，如果這應該是積極的。

I can't speak to the entire product profile, but from a glycemic control perspective, it goes without saying from a regulatory perspective, we need to show more and better glycemic control than in semaglutide monotherapy.

我無法談論整個產品概況，但從血糖控制的角度來看，從監管的角度來看，不言而喻，我們需要展示比索馬魯肽單藥治療更多更好的血糖控制。

Thank you, Martin. And on the 483 and the contract manufacturing organization for Wegovy, that's right, we expect to be able to supply the U.S. market in the second half, which implies that manufacturing will be up running in Q2 for us to fill up the supply chain before we get back and promote in the market. And to be able to resume manufacturing in Q2, there are 2 category of activities that needs to be completed. One is -- and that's built on the observations you can read about in the 483. One is in the camp of, say, procedural aspects, updates to the quality management system, training of employees, et cetera, that's not on a critical path. And then there are activities linked to maintenance in the facility, and you mentioned changing some fillers yourself. Those fillers are available now, which is an achievement in itself in a market where supply chains are stressed. But the fillers are in place.

謝謝你，馬丁。 483 和 Wegovy 的代工製造機構，沒錯，我們預計下半年能夠供應美國市場，這意味著製造將在 Q2 開始運行，以便我們在我們之前填補供應鏈。回來並在市場上推廣。為了能夠在第二季度恢復生產，需要完成兩類活動。一個是 - 這是建立在您可以在 483 中閱讀的觀察結果的基礎上。一個是在程序方面、質量管理體系更新、員工培訓等方面的陣營，這不是關鍵路徑.然後還有與設施維護相關的活動，你提到自己更換一些填充物。這些填料現在已經上市，這在供應鏈受到壓力的市場中本身就是一項成就。但是填充物已經到位。

And what is, say, the critical remaining aspect is the media fill. Whenever you have taken down manufacturing set up, you have to requalify it and you have to run a media fill proving under stressful conditions that the line is operating with integrity and producing sterile products. So that's an important step. It's a standard thing. All manufacturers operating with sterile manufacturing are used to doing that. We do it on our own lines on a regular basis. There's always a risk because you do this under stressful conditions.

比如說，剩下的關鍵方面是媒體填充。每當您拆除製造設備時，您都必須對其進行重新認證，並且您必須在壓力條件下運行培養基填充，以證明該生產線正在以完整性運行並生產無菌產品。所以這是重要的一步。這是一個標準的東西。所有從事無菌生產的製造商都習慣於這樣做。我們定期在自己的生產線上進行。總是有風險，因為你是在壓力大的情況下這樣做的。

So if there's a failed media fill, you have to do it again. But this is something you can do in a matter of weeks, not months. So we feel that there's good progress, that there's a competent contract manufacturing organization handling this. They know what they have to do, and we believe they can do it. There is, of course, always risk, but we think this is manageable. And we feel we have good confidence in our ability to resupply in the second half of the year.

因此，如果介質填充失敗，您必須重新進行。但這是您可以在幾週內完成的事情，而不是幾個月。所以我們覺得有很好的進展，有一個稱職的合同製造組織來處理這個問題。他們知道他們必須做什麼，我們相信他們可以做到。當然，風險總是存在的，但我們認為這是可控的。我們認為我們對下半年的補給能力充滿信心。

Our next question comes from Michael Leuchten with UBS.

我們的下一個問題來自瑞銀的 Michael Leuchten。

Michael Leuchten from UBS. Two questions for Martin, please. Firstly, Martin, can you just confirm that you have all the Mim8 data now for the Phase III. You were saying you're going to start recruiting patients into the Mim8 in the second half, but it wasn't entirely clear whether there's still some data outstanding that you need from the Phase I, Phase II trial or whether you have everything that you need.

瑞銀的邁克爾·勒赫滕。請給馬丁兩個問題。首先，Martin，您能否確認您現在擁有第三階段的所有 Mim8 數據。您說您將在下半年開始招募患者進入 Mim8，但目前尚不完全清楚您是否仍然需要從 I 期、II 期試驗中獲得一些未完成的數據，或者您是否擁有您所需要的一切需要。

And the second question on icosema. I was wondering if you could talk to what you learned from Xultophy and the lack of success for that product as you try to apply the same concept. I think there were some challenges with the lack of [separate] titration. I was wondering if you're aiming to address that in the clinical trial program or if that's our program as it looks for now what was the -- what effectively you did with Xultophy.

以及關於icosema的第二個問題。我想知道您是否可以談談您從 Xultophy 中學到的東西，以及當您嘗試應用相同的概念時該產品缺乏成功。我認為缺乏[單獨]滴定存在一些挑戰。我想知道您是否打算在臨床試驗計劃中解決這個問題，或者這是否是我們的計劃，因為它現在正在尋找什麼是 - 您使用 Xultophy 有效地做了什麼。

Absolutely. Thanks very much, Michael. So first of all, on Mim8, as you know, we run sort of a combined Phase I/II study with a number of single ascending doses and then a number of multiple ascending doses. During the course of Q4 of last year, we started to see the readout of some of the earlier multiple ascending doses. They actually called for us to sort of, at that dose level, see a safe and tolerable profile as well as a pharmacokinetic profile that allows us to at-risk actually initiate recruitment into Phase III already in Q4 of last year. So we have started recruiting patients. They are what we call in a run-in period where we observe them on their current medication and we aim to initiate actual treatment in second half of this year.

絕對地。非常感謝，邁克爾。因此，首先，如您所知，在 Mim8 上，我們進行了一項 I/II 期聯合研究，其中包含多個單次遞增劑量，然後是多個多次遞增劑量。在去年第四季度，我們開始看到一些早期多次遞增劑量的讀數。他們實際上要求我們在該劑量水平上看到一個安全和可耐受的概況以及藥代動力學概況，使我們能夠在去年第四季度實際開始招募進入 III 期。所以我們開始招募病人。他們就是我們所說的磨合期，我們觀察他們目前的用藥情況，我們的目標是在今年下半年開始實際治療。

This approach obviously allows us to cut time. So at the time point where we have the full readout of the Phase I/II trial and have interacted with the regulatory authorities, most patients will be recruited. And therefore, we can go directly into the dosing part in the second half. That actually allows us to almost cut the full development part of Mim8 R&D sort of time in half. So instead of the normal 7 to 8 years development time in the clinical phase, we actually aim to have 4 years from first human dose to a final dose in Phase III for Mim8. So this is an at-risk approach, but we are actually already now recruiting patients into the study.

這種方法顯然可以讓我們縮短時間。因此，在我們獲得 I/II 期試驗的完整讀數並與監管機構互動的時間點，大多數患者將被招募。因此，我們可以在下半場直接進入加藥部分。這實際上使我們幾乎可以將 Mim8 研發的全部開發部分時間減半。因此，與臨床階段正常的 7 至 8 年開發時間不同，我們實際上的目標是從第一個人體劑量到 Mim8 的 III 期最終劑量有 4 年的時間。所以這是一種有風險的方法，但實際上我們現在已經在招募患者參加這項研究。

On icosema, I think that's sort of a combined question to myself and Camilla. Obviously, on the clinical profile, what we saw on Xultophy was very, very attractive. And it was actually easy to try to create and physicians who have initiated patients on Xultophy do not find any issues in not -- in having sort of the fixed-dose combination because when combining a GLP-1 analog and an insulin, you actually mitigate the tolerability issues that you see with the mono components. So that combination leaves for less gastrointestinal side effects from the GLP-1 component and less risk of hypoglycemia from the insulin component.

關於icosema，我認為這對我和卡米拉來說是一個綜合問題。顯然，在臨床概況上，我們在 Xultophy 上看到的非常非常有吸引力。它實際上很容易創建，並且已經開始使用 Xultophy 患者的醫生沒有發現任何問題——在固定劑量組合中，因為當組合 GLP-1 類似物和胰島素時，你實際上減輕了您在單聲道組件中看到的耐受性問題。因此，這種組合可以減少 GLP-1 成分的胃腸道副作用和胰島素成分的低血糖風險。

That makes it an attractive clinical offering. And obviously, we need to be even better in the icosema Phase III to secure a very clear but also a very simple titration, reaching the good efficacy and the good safety profile but then, obviously, also, again, calling out the convenience aspect. And normally, I wouldn't call out convenience, but in the case of icosema that has the ability to go in and sort of compete with insulin basal bolus treatment, we are talking about moving from 28 weekly injections to 1 weekly injection. I think even for me who wants to normally focus only on efficacy and safety, that is a convenience play that is quite substantial and will have an impact on patients and actually also treating physicians.

這使它成為一種有吸引力的臨床產品。顯然，我們需要在 icosema 第三階段做得更好，以確保非常清晰但也非常簡單的滴定，達到良好的療效和良好的安全性，但顯然，同樣，再次強調便利性方面。通常情況下，我不會說方便，但對於有能力進入並與胰島素基礎推注治療競爭的 icosema，我們正在談論從每週 28 次注射轉變為每週注射 1 次。我認為即使對於我通常只關注功效和安全性的我來說，這也是一種相當重要的便利遊戲，將對患者產生影響，實際上也會對治療醫生產生影響。

Maybe Camilla also wants to talk a little bit on how we intend to go with icosema vis-a-vis Xultophy.

也許卡米拉還想談談我們打算如何使用 icosema 和 Xultophy。

Yes. I just wanted to say that there is, of course, an increased demand for these types of combinations, especially now in China, we just had Xultophy approved in October 2021, and we will be focusing significantly on that also in China. But also in Region Japan, we see a very steep increase in the usage of Xultophy, same in other parts of Latin America, but also in East Asia. So there is a very good and underlying demand for Xultophy at the moment. And of course, that also gives us good hope for icodec and icosema.

是的。我只想說，當然，對這些類型的組合的需求在增加，尤其是現在在中國，我們剛剛在 2021 年 10 月獲得了 Xultophy 的批准，我們也將在中國重點關注這一點。但在日本地區，我們看到 Xultophy 的使用量急劇增加，拉丁美洲其他地區和東亞地區也是如此。因此，目前對 Xultophy 有很好的潛在需求。當然，這也給了我們對 icodec 和 icosema 的良好希望。

Thank you, Martin. Thank you, Camilla, and thank you, Michael, for the questions.

謝謝你，馬丁。謝謝你，卡米拉，謝謝你，邁克爾，提出問題。

Our next question comes from Rajan Sharma with Deutsche Bank.

我們的下一個問題來自德意志銀行的 Rajan Sharma。

It's Rajan Sharma at Deutsche Bank. First one just on icodec. Could you just kind of think about the commercial opportunity there? So basal insulin was obviously flat globally in 2021. And so how are you thinking about the icodec opportunity? And the potential to return the franchise to growth, obviously, once we get through VBP.

我是德意志銀行的 Rajan Sharma。第一個只是在編解碼器上。你能想一想那裡的商業機會嗎？因此，2021 年全球基礎胰島素明顯持平。那麼您如何看待 icodec 機會？顯然，一旦我們通過 VBP，特許經營權恢復增長的潛力。

And then the second was just a clarification on the Wegovy supply. Could you just confirm that you don't need a -- or the plant doesn't need a reinspection?

然後第二個只是對 Wegovy 供應的澄清。您能否確認您不需要 - 或者工廠不需要重新檢查？

Thank you, Raj. And Camilla first on the commercial aspects on icodec.

謝謝你，拉傑。卡米拉首先談到了 icodec 的商業方面。

Yes, icodec. We're looking forward to bringing icodec to the market, obviously, because it has a number of significant advantages for patients, in particular, that we can reduce the number of injections from 7 to 1 a week, obviously. Having said that, we also are looking at potentially, of course, increasing our share in the basal segment, which we traditionally have not had the same market share as in the other insulin segment.

是的，編解碼器。顯然，我們期待將 icodec 推向市場，因為它對患者有許多顯著優勢，特別是我們可以將每週注射次數從 7 次減少到 1 次，顯然。話雖如此，我們當然也在考慮增加我們在基礎領域的份額，我們傳統上沒有與其他胰島素領域相同的市場份額。

And in addition to that, we also hope that the ease of use with icodec and the efficacy of it can help expand the market further. So lots of benefits for us in bringing icodec to the market, and we look forward to that a few years down the road.

除此之外，我們也希望 icodec 的易用性和它的功效能夠幫助進一步擴大市場。將 icodec 推向市場對我們來說有很多好處，我們期待在未來幾年內實現這一目標。

Thank you, Camilla. And on Wegovy reinspection, yes, it is our understanding that it's not required to conduct a reinspection and the U.S. FDA would have a look at the facility at the next regular inspection, whenever that will take place.

謝謝你，卡米拉。在 Wegovy 的重新檢查中，是的，我們的理解是不需要進行重新檢查，美國 FDA 將在下次定期檢查時查看該設施，無論何時進行。

And I'd also like to add that we are also bringing in line more sites as part of the production expansion strategy. So more sites will come in line over the next year or so. So we believe we have a robust and future-proof supply setup for Wegovy.

我還想補充一點，作為生產擴張戰略的一部分，我們還將引入更多站點。所以在接下來的一年左右會有更多的網站上線。因此，我們相信我們為 Wegovy 提供了強大且面向未來的供應設置。

Our next question comes from Wimal Kapadia with Bernstein.

我們的下一個問題來自 Wimal Kapadia 和 Bernstein。

So just one for Martin. There's a lot of competitive data this year. But in particular, I wanted to ask about the BI-Zealand dual agonist and the Lilly triagonist. Now these targets that Novo have looked at in the past and did not pursue. You kind of said the same with GIP, but now obviously, you've restarted that program. So just curious, particularly about these 2 programs, the GLP-1 and glucagon combo and the triagonist, why you have conviction that they were not worth the investment at the time and is this something you would reconsider depending on what happens with the competition data?

所以只給馬丁一個。今年有很多競爭數據。但特別是，我想問一下 BI-Zealand 雙重激動劑和禮來三方劑。現在這些目標，諾和過去都看在眼裡，沒有去追求。您對 GIP 也說過同樣的話，但現在顯然，您已經重新啟動了該程序。所以只是好奇，特別是關於這兩個程序，GLP-1 和胰高血糖素組合以及三對角線，為什麼你確信它們當時不值得投資，這是你會根據競爭數據發生的情況重新考慮的事情?

And then my second question is maybe for Camilla. It's one I've kind of asked before, but now we're getting close to the time, so maybe you have a different view. But just on pricing for Ozempic high dose that we're getting potentially the approval in March. But the net pricing of Ozempic is still around $18, according to my math. And Saxenda -- and Wegovy, assuming similar to Saxenda, will be over $30 net price. So should we just be thinking about splitting the difference when we're thinking about Ozempic high dose or would you take a slightly different strategy? And I am asking because from a time line perspective, you may be on the market with a high dose before tirzepatide is launched in diabetes.

然後我的第二個問題可能是針對卡米拉的。這是我之前問過的一個問題，但現在我們的時間越來越近了，所以也許你有不同的看法。但僅就 Ozempic 高劑量的定價而言，我們可能會在 3 月份獲得批准。但根據我的數學計算，Ozempic 的淨定價仍然在 18 美元左右。 Saxenda 和 Wegovy，假設與 Saxenda 相似，淨價將超過 30 美元。那麼，當我們考慮 Ozempic 高劑量時，我們應該只是考慮分開差異，還是您會採取稍微不同的策略？我之所以問，是因為從時間線的角度來看，在替西帕肽用於糖尿病治療之前，您可能已經在市場上以高劑量上市。

Thank you, Wimal. So first, Martin, on the competitive front with dual and triagonist.

謝謝你，維馬爾。所以首先，馬丁，在對偶和三角的競爭前線。

Yes. Thanks very much, Wimal. So when we make our portfolio decisions, obviously, we look at our overall strategy but we also look at our clinical profiles. And as you alluded to yourself, we've had both dual and triagonist in our pipeline. And we have to say that on balance, looking at efficacy, looking at safety profiles, we found that this is obviously also what you see in our portfolio right now. The combination of an amylin agonist together with a GLP-1 agonist to be substantially more attractive than what a dual, triagonist in the GIP glucagon space could offer.

是的。非常感謝，維馬爾。因此，當我們做出投資組合決策時，顯然，我們會查看我們的整體戰略，但我們也會查看我們的臨床資料。正如你提到的那樣，我們的管道中有雙重和三邊形。我們不得不說，總的來說，看看功效，看看安全性，我們發現這顯然也是你現在在我們的產品組合中看到的。胰淀素激動劑與 GLP-1 激動劑的組合比 GIP 胰高血糖素空間中的雙重三激動劑更具吸引力。

I think it's reasonable to say they will be effective. But what we've seen is also that, that efficacy comes with a safety cost. So on balance, there was a decision that made a lot of sense or it makes a lot of sense to us. Obviously, we also have to safeguard, there's always attrition in what we do. And therefore, we also put a bet in on a GLP-1/GIP agonist and aiming to have the best GLP-1 agonist and the best GIP agonist, obviously, that could also be an attractive offering.

我認為有理由說它們會有效。但我們也看到，這種功效伴隨著安全成本。所以總的來說，有一個決定很有意義，或者對我們來說很有意義。顯然，我們還必須保護，我們所做的事情總會有損耗。因此，我們還押注了 GLP-1/GIP 激動劑，目標是擁有最好的 GLP-1 激動劑和最好的 GIP 激動劑，顯然，這也可能是一個有吸引力的產品。

Thank you, Martin. Camilla, on pricing Ozempic high dose versus Wegovy.

謝謝你，馬丁。卡米拉，關於 Ozempic 高劑量與 Wegovy 的定價。

Wimal, we are, of course, looking forward to getting the approval also in the U.S. of Ozempic 2.0. Have to say, of course, Ozempic is a great product. You saw how good the penetration we had last year. And there is 80% of people getting good control with Ozempic 1.0. There might be a remaining group of people that could benefit from intensifying to 2.0. So that's why we look forward to bringing that to the market.

Wimal，我們當然期待在美國也獲得 Ozempic 2.0 的批准。不得不說，當然，Ozempic 是一款很棒的產品。你看到我們去年的滲透率有多好。並且有 80% 的人使用 Ozempic 1.0 獲得了良好的控制。可能還有一部分人可以從強化到 2.0 中受益。這就是為什麼我們期待將其推向市場的原因。

In terms of pricing and net pricing and differences between diabetes and obesity, this is not something I can get into the details of at this point in time. But clearly, to say that for now, we have Wegovy on the market in the U.S. in obesity recognized for that indication. And then we have Ozempic for people with diabetes in the U.S. at 2 different price points for 2 different indications and 2 different groups of people. So more to come on that when we have the approval of Ozempic 2.0.

在定價和淨定價以及糖尿病和肥胖症之間的差異方面，這不是我目前可以深入了解的細節。但很明顯，就目前而言，我們在美國市場上的 Wegovy 肥胖症已被認可為這一跡象。然後我們有針對美國糖尿病患者的 Ozempic，針對 2 個不同的適應症和 2 個不同的人群，有 2 個不同的價格點。因此，當我們獲得 Ozempic 2.0 的批准時，還有更多的事情要做。

And you might have to ask for a third time, Wimal, sometime in the future.

Wimal，在未來的某個時候，你可能不得不第三次詢問。

Our next question comes from Keyur Parekh with Goldman Sachs.

我們的下一個問題來自高盛的 Keyur Parekh。

A few, if I may. The first one is just following up on a couple of the previous questions. One, as you think about the headline data we see from tirzepatide, what is your base case expectation for kind of the amount of weight loss we see with that agent? What do you think would be an upside and a downside surprise to your base case?

幾個，如果可以的話。第一個只是對前面幾個問題的跟進。第一，當您考慮我們從 tirzepatide 看到的標題數據時，您對我們使用該藥物看到的減重量的基本情況預期是什麼？您認為對您的基本案例來說，有什麼好處和壞處？

Secondly, as you think about positioning icosema, both kind of from a regulatory perspective and from a commercial perspective, I'm kind of surprised you're not running a head-to-head versus Xultophy. So I would be keen to understand why you're not doing that.

其次，當您從監管角度和商業角度考慮定位 icosema 時，我有點驚訝您沒有與 Xultophy 正面交鋒。所以我很想知道你為什麼不這樣做。

And from a regulatory perspective, are you still expecting this molecule to be used post kind of failure with GLP-1 and basal insulin? Or do you think this can be moved earlier in the treatment paradigm?

從監管的角度來看，您是否仍然期望這種分子在 GLP-1 和基礎胰島素失敗後使用？或者您認為這可以在治療範式中更早地進行嗎？

And then lastly, Camilla, for you, 55% kind of obesity growth in 2021. As we look at 2022, is it fair to assume that your growth rate will be higher than that for the full year?

最後，卡米拉，對你來說，2021 年肥胖增長 55%。當我們展望 2022 年時，假設你的增長率將高於全年，這是否公平？

Thank you, Keyur. And let me try to give a bit perspective from my side on tirzepatide and then perhaps, Martin, you can add -- or I don't know, Camilla, if you can add on commercial.

謝謝你，凱爾。讓我嘗試從我的角度對 tirzepatide 給出一些看法，然後也許，馬丁，你可以添加 - 或者我不知道，卡米拉，你是否可以添加商業廣告。

But I think Camilla alluded a bit to the momentum we have right now with Ozempic. You have all seen what Wegovy did when it was launched in the U.S. So I feel we have a really, really good proposition in what we have at hand based on the semaglutide molecule. We have higher dose. We have a broad portfolio in obesity. So this is really about expanding the market.

但我認為卡米拉暗示了我們現在與 Ozempic 合作的勢頭。你們都看到了 Wegovy 在美國推出時所做的事情。所以我覺得我們手頭有一個基於 semaglutide 分子的非常非常好的建議。我們有更高的劑量。我們在肥胖方面擁有廣泛的產品組合。所以這實際上是關於擴大市場。

And I think there's -- I hope there's room for both products, but I would know for sure that there's room for Ozempic and Wegovy because that's established already now. And the feedback we get from both physicians and patients in terms of what it does for them, both Ozempic and Wegovy, is amazing.

而且我認為 - 我希望這兩種產品都有空間，但我肯定知道 Ozempic 和 Wegovy 有空間，因為現在已經確定了。我們從醫生和患者那裡得到的關於它為 Ozempic 和 Wegovy 所做的事情的反饋是驚人的。

So I think we are building the go-to brands here that is not necessarily going to be easy to compete against. Having said that, I have a high respect for Eli Lilly as a competitor and I think they will give it their best shot. But we have a very solid ground and I feel comfortable about that. I don't know if, Martin, you want to speculate on their positioning.

所以我認為我們正在這裡建立不一定容易競爭的首選品牌。話雖如此，我非常尊重禮來公司作為競爭對手，我認為他們會全力以赴。但我們有一個非常堅實的基礎，我對此感到很自在。我不知道，馬丁，你是否想推測他們的定位。

I can only echo what you said. I don't think I should be speculating on their positioning. But I think it would be fair that -- to say that I look much forward to see what their label is going to look like. As you know, we all look at different estimates, treatment policy versus trial product estimate. And in a label, those data may look a little bit different and maybe less impressive than what we had seen so far. So I'm looking forward to see the label to see the actual difference on both glycemic control and also weight.

我只能附和你說的。我認為我不應該猜測他們的定位。但我認為這是公平的——說我非常期待看到他們的標籤會是什麼樣子。如您所知，我們都關注不同的估計，治療政策與試驗產品估計。在標籤中，這些數據可能看起來有點不同，可能不如我們目前看到的那麼令人印象深刻。所以我期待看到標籤，看看血糖控制和體重的實際差異。

And then obviously, weighing that up against the safety profile, we know that semaglutide, to Lars' point, it's on the market. It's super well perceived. And that is in part because of an attractive safety profile.

然後很明顯，將其與安全性進行權衡，我們知道在 Lars 看來，semaglutide 已經上市。感覺超級好。這部分是因為有吸引力的安全配置文件。

We've seen quite a high withdrawal rate from some of the tirzepatide studies, even in the face of low withdrawal rates of semaglutide in the same study. So I think on balance, semaglutide will hold its ground on the combination of attractive efficacy getting 75% to 80% to target and then obviously on a very attractive safety profile. And then obviously, with a fast follow-on from our side in the shape of Cagrisema.

我們從一些 tirzepatide 研究中看到了相當高的退出率，即使在同一項研究中索馬魯肽的退出率很低。因此，我認為總的來說，semaglutide 將在具有吸引力的療效組合上保持其基礎，達到 75% 至 80% 的目標，然後顯然具有非常有吸引力的安全性。然後很明顯，我們這邊以Cagrisema的形式快速跟進。

Thank you, Martin. Camilla, there was a second question on obesity growth, where we see growth now, a bit north of 50%. While we don't guide specifically on growth rates per category, what are your perspectives on that?

謝謝你，馬丁。卡米拉，還有關於肥胖增長的第二個問題，我們現在看到增長，略高於 50%。雖然我們沒有具體指導每個類別的增長率，但您對此有何看法？

Yes. So the perspectives are that the first year of COVID-19, we did see a dip in the obesity growth because people were not going to see the doctor. However, in the meantime, there has been an increased understanding that it is important to treat obesity. We even saw studies where it was proven that the risk of death for people living with obesity getting COVID-19 was significantly higher. So the understanding from payers, health care authorities and providers that it is important to treat obesity because of the risk of long-term complications such as cardiovascular disease and diabetes and some types of cancer is extremely important.

是的。因此，觀點是，在 COVID-19 的第一年，我們確實看到了肥胖增長的下降，因為人們不會去看醫生。然而，與此同時，人們越來越認識到治療肥胖很重要。我們甚至看到研究證明，肥胖症患者感染 COVID-19 的死亡風險明顯更高。因此，付款人、醫療保健機構和提供者的理解是，治療肥胖很重要，因為存在心血管疾病、糖尿病和某些類型癌症等長期並發症的風險，這一點非常重要。

And I think also in our numbers as of last year, you see that, that understanding also turns into more prescriptions. And especially with Wegovy even so also a patient-driven demand for a weight-loss product in the range of 17% to 18% like Wegovy. So the underlying dynamics in obesity is positive when it comes to treatment getting to patients. And of course, that general momentum, I think, is important to rely on. And without giving any indications of growth rates for this year because that obviously also depends a lot on exactly the time of which we will be back with the full supply for the U.S. and so on.

而且我認為在我們去年的數據中，你會看到，這種理解也變成了更多的處方。尤其是 Wegovy，即使如此，患者對減肥產品的需求也在 17% 到 18% 之間，比如 Wegovy。因此，在對患者進行治療時，肥胖的潛在動力是積極的。當然，我認為，這種總體勢頭很重要。並且沒有給出今年增長率的任何跡象，因為這顯然也很大程度上取決於我們將在什麼時候為美國提供全部供應等等。

Good. Thank you, Camilla. Thank you, Keyur.

好的。謝謝你，卡米拉。謝謝你，凱爾。

Lars, sorry, can I -- sorry, I thought there was another question on the positioning for icosema, regulatory and commercial. Sorry.

Lars，抱歉，我可以-- 抱歉，我認為對於icosema、監管和商業的定位還有另一個問題。對不起。

Yes. So basically, for icosema, we aim at a simple and convenient once-weekly treatment and it basically means that we hope to be able to be an alternative to base bolus insulin at a similar HbA1c. And of course, just with fewer injections and also a good weight profile, a good [hypo] profile and an efficient HbA1c profile. So that's how we see icosema being used. And in particular, in the regions of Europe, of Asia and also the Middle East, and I already talked to earlier, Japan and China being very important for fixed-dose combinations of insulin and GLP-1.

是的。所以基本上，對於 icosema，我們的目標是簡單方便的每週一次治療，這基本上意味著我們希望能夠在相似的 HbA1c 下替代基礎推注胰島素。當然，只需更少的注射、良好的體重曲線、良好的 [hypo] 曲線和有效的 HbA1c 曲線。這就是我們看到使用icosema的方式。特別是在歐洲、亞洲和中東地區，我之前已經談過，日本和中國對於胰島素和 GLP-1 的固定劑量組合非常重要。

Good. Thank you. I hope that satisfied you, Keyur.

好的。謝謝你。我希望你滿意，Keyur。

Our next question comes from Simon Baker with Redburn.

我們的下一個問題來自 Redburn 的 Simon Baker。

Two, if I may, please. Firstly, for you, Camilla, just going back to your comments on Xultophy demand. You cited a number of regions and countries where you're seeing increased demand for the combination. Flipping that on its head, I wonder if you could give us your thoughts on why there isn't increased demand in other regions. What's holding back? Is it physician preference? Is it reimbursement? Some thoughts on that would be very helpful.

二，如果可以的話，請。首先，對於您，Camilla，回到您對 Xultophy 需求的評論。您列舉了一些地區和國家/地區對這種組合的需求增加的情況。顛倒過來，我想知道你是否可以給我們你的想法，為什麼其他地區的需求沒有增加。什麼阻礙了？是醫生偏好嗎？是報銷嗎？對此的一些想法將非常有幫助。

And then for Martin, going back to something that was touched on yesterday, the sema-GIP combo study, the Phase II that started in November. I see that, that study is due to report out in October or finishing October. That seems a little early. So I just wonder if you could give us any thoughts on that. And also on the dose selection of the GIP that you picked, in that it seems quite a broad range from, I think, 2.4 to 21.6 milligrams.

然後對 Martin 來說，回到昨天提到的 sema-GIP 組合研究，即 11 月開始的第二階段。我看到了，該研究將於 10 月或 10 月完成報告。這似乎有點早。所以我想知道你是否可以給我們一些想法。還有關於你選擇的 GIP 的劑量選擇，我認為它似乎範圍很廣，從 2.4 到 21.6 毫克。

Thank you, Simon. So Camilla first on Xultophy demand and flipping it on the head, why not all regions.

謝謝你，西蒙。所以卡米拉首先談到了 Xultophy 的需求，然後把它放在了頭上，為什麼不是所有地區。

Yes, why not all regions. So in the regions where we don't see a strong uptake of Xultophy, it's basically because there has been a traditional preference for loose combinations of products, especially in the U.S. So that's really the reason.

是的，為什麼不是所有地區。因此，在我們沒有看到 Xultophy 被強烈吸收的地區，這基本上是因為傳統上偏愛產品的鬆散組合，尤其是在美國。所以這就是真正的原因。

On the other hand, we see in other countries like China, there's been a long tradition for using combination insulin and mixed insulin. So it is down to preference to a large extent. And that's also why for our insulins for a number of years, we work with what we call the market fit approach to be able to supply the market with the type of insulin that is generally preferred from the doctors and the population.

另一方面，我們在中國等其他國家看到，使用聯合胰島素和混合胰島素的傳統由來已久。所以很大程度上取決於偏好。這也是為什麼我們的胰島素多年來一直採用我們所謂的市場匹配方法，以便能夠為市場提供醫生和人群普遍偏愛的胰島素類型。

Thank you, Camilla. Martin, on sema-GIP time line and also dose of GIP?

謝謝你，卡米拉。馬丁，在 sema-GIP 時間線和 GIP 劑量上？

Yes, thanks very much. So as you rightly called out, this is a Phase II study. And therefore, time lines are designed to allow us to look at efficacy, safety, but actually also doing the dose finding. And that means, obviously, that we have made time lines as short as we can to allow us to have those readouts.

是的，非常感謝。因此，正如您正確指出的那樣，這是一項 II 期研究。因此，時間線旨在讓我們查看功效、安全性，但實際上也進行劑量發現。顯然，這意味著我們已經盡可能縮短了時間線，以允許我們獲得這些讀數。

The sema-GIP offering is going to be a fixed dose combination, and that also means that we need to test different doses of GIP up against the backbone of semaglutide. And that basically means that we have to explore a range to secure that we obviously investigate the optimal efficacy, but also to secure proper safety and that does call for a quite wide range of dose testing in that setting.

sema-GIP 產品將是一個固定劑量的組合，這也意味著我們需要針對 semaglutide 的骨幹測試不同劑量的 GIP。這基本上意味著我們必須探索一個範圍，以確保我們明顯研究最佳療效，同時確保適當的安全性，這確實需要在該環境中進行相當廣泛的劑量測試。

Our next question comes from Peter Welford with Jefferies.

我們的下一個問題來自 Jefferies 的 Peter Welford。

Just returning to Wegovy, a couple here. Firstly, just with regards to the CMO. Just so I can understand, is Novo going to do their inspection from your side working with Catalent before the facility comes back online? And I guess it'd be helpful if you could provide something as to what Novo has been doing during this process from your side to resolve this issue.

剛回到韋戈維，這裡有一對。首先，關於 CMO。順便說一下，Novo 是否會在設施重新上線之前與 Catalent 合作進行檢查？我想如果你能提供一些關於 Novo 在這個過程中從你身邊所做的事情來解決這個問題會很有幫助。

And then secondly, just on the PDS290 FlexTouch platform. Apologies if I missed this yesterday. Could you just explain again why that is an ex-U.S. platform and is not being pursued in the U.S. at this time? And equally, the additional sites that you say will come online in the next year or so. Are these sites going to be -- to provide drug to both the U.S. and Europe? Or will these sites be specifically to meet the future U.S. demand that there is?

其次，就在 PDS290 FlexTouch 平台上。抱歉，如果我昨天錯過了這個。你能再解釋一下為什麼那是前美國嗎？平台，目前不在美國追捧？同樣，您所說的其他網站將在明年左右上線。這些網站是否會向美國和歐洲提供藥物？或者這些網站是否會專門滿足美國未來的需求？

And then could I just ask just on the copay card. I appreciate, obviously, understandably, they've been withdrawn at the moment. When the drug is brought back again in the second half and presumably there's going to be significant pent-up demand that's accumulated during the last 6 months. Should we assume then copay cards will come back in earnest? Or do you think, given you had 6 months also to improve payer coverage and access, we should assume that copay cards will perhaps be less material to an extent versus the original Wegovy launch back in last year?

然後我可以只在共付卡上問一下嗎？我很感激，顯然，可以理解的是，他們目前已被撤回。當該藥物在下半年再次被帶回時，可能會在過去 6 個月中積累大量被壓抑的需求。我們是否應該假設共付卡會認真回來？還是您認為，鑑於您還有 6 個月的時間來改善付款人的覆蓋範圍和訪問權限，我們應該假設與去年最初推出的 Wegovy 相比，共付卡可能在一定程度上不那麼重要？

All right. Thank you, Peter. Let me try to give your questions a shot here. So on the Wegovy contract manufacturer, we have a very good partnership with the company. Obviously, we were disappointed about the situation they ended up in after the inspection from the U.S. FDA. But we are very pleased with the professionalism whereby they are handling this. We work closely together with them. I cannot go into all the details of what that involves. But we are close to the situation, and we feel very comfortable in how they are handling it. And as such, this is a partnership, and we are not going to do a formal inspection of what they do because we're close to it.

好的。謝謝你，彼得。讓我在這裡試一試你的問題。所以在 Wegovy 合同製造商上，我們與公司有著非常好的合作夥伴關係。顯然，我們對他們在美國 FDA 檢查後的結果感到失望。但我們對他們處理此事的專業精神感到非常滿意。我們與他們密切合作。我無法深入了解其中涉及的所有細節。但我們已經了解情況，我們對他們的處理方式感到非常自在。因此，這是一種合作夥伴關係，我們不會對他們的工作進行正式檢查，因為我們已經接近了。

On the PDS290 platform, we felt it would be a good idea for us to register 1 more, say, technology platform, so to say. The platform in the U.S. is based on a single shot device and a syringe inside that, that is filled by -- mainly speaking, by our contract manufacturing partners. We can do a bit in-house, but that's mainly outsourced.

在PDS290平台上，我們覺得多註冊1個，比如說技術平台，可以這麼說是個好主意。美國的平台基於單次注射裝置和內部注射器，主要由我們的合同製造合作夥伴填充。我們可以在內部做一些事情，但這主要是外包的。

The PDS290 platform is an in-house [no noise] platform. So that's something we fill and pack ourselves. So when we add new sites for Wegovy supply, that is for the single shot presentation, i.e., what we have in the U.S. market today. What platform will end up using in other markets remains to be seen, but we are adding strategic flexibility in having more platforms.

PDS290 平台是一個內部 [無噪音] 平台。所以這是我們自己填充和打包的東西。因此，當我們為 Wegovy 供應添加新站點時，即用於單次演示，即我們今天在美國市場上擁有的內容。最終將在其他市場使用什麼平台還有待觀察，但我們正在增加擁有更多平台的戰略靈活性。

On the copay card, you're right. They were established at the time of launch, a large success in generating attention to Wegovy and interest in Wegovy. We have stopped it again, and they will eventually run out of time, so to say, we feel that there's good awareness about the products. So when we launch it again or when we start -- well, it is in the market still. But when we start promoting it again, we need less of that type of support to it without going into all the details about what our plans are. But we think that the awareness about Wegovy, the willingness to prescribe and seek care is high.

在copay卡上，你是對的。它們是在發佈時建立的，在引起對 Wegovy 的關注和對 Wegovy 的興趣方面取得了巨大成功。我們又停止了，他們最終會用完時間，所以可以說，我們覺得對產品有很好的認識。因此，當我們再次推出它或開始時——嗯，它仍在市場上。但是當我們再次開始推廣它時，我們需要的那種支持就會減少，而不需要詳細了解我們的計劃是什麼。但我們認為對 Wegovy 的認識、開處方和就醫的意願很高。

Our next question comes from Simon Mather with BNP Paribas.

我們的下一個問題來自法國巴黎銀行的 Simon Mather。

Kind of following on from that in terms of Wegovy demand, you don't see the need for copay cards. Maybe you can help us just understand because numerous times, you said you expect to have unconstrained supply for the second half of the year in the U.S. if all things go to plan. Can you help us get a sense as to what you believe the actual underlying demand for the product is because one would assume with the copay card, availability is clearly a "no-brainer" for people to want the drug when you can get a 6-month supply for $150. And so just any kind of sense as to what you think an underlying demand curve for Wegovy would be in a normal non-GIP treatment option would be. That would be helpful.

就 Wegovy 的需求而言，您看不到共付卡的需求。也許您可以幫助我們理解，因為您多次說過，如果一切按計劃進行，您預計美國下半年的供應將不受限制。您能否幫助我們了解您認為對該產品的實際潛在需求是什麼，因為人們會假設使用共付卡，當您可以獲得 6 -每月供應 150 美元。因此，對於您認為在正常的非 GIP 治療方案中 Wegovy 的潛在需求曲線將是什麼的任何感覺。那會很有幫助。

And then maybe just -- sorry, maybe just on Cagrisema, if you could help us understand. The amylin has previously been shown to cause large hypoglycemic events. I'm just wondering if that's part of the go, no-go decision? And can you remind us the degree of hypoglycemia you may have seen in the obesity trials? Just trying to get a sense for your level of confidence.

然後也許只是 - 對不起，也許只是在 Cagrisema，如果你能幫助我們理解的話。胰淀素先前已被證明會引起大的低血糖事件。我只是想知道這是否是去，不去決定的一部分？你能提醒我們你在肥胖試驗中看到的低血糖程度嗎？只是想了解您的自信程度。

So thank you, Simon. So on Wegovy underlying demand, you can say, we -- I want to mention is that we are building the market access. So we have brought support by the 3 big PBMs, but we still have to have employees opting in. So compared to when we launched mid-summer, obviously, we have been working hard in getting, say, effective access up. So that's obviously something that comes in as a benefit when we launch again.

所以謝謝你，西蒙。所以關於 Wegovy 的潛在需求，你可以說，我們——我想提的是，我們正在建立市場准入。因此，我們帶來了 3 大 PBM 的支持，但我們仍然必須讓員工選擇加入。因此，與我們在仲夏推出時相比，顯然，我們一直在努力獲得有效的訪問權限。因此，當我們再次啟動時，這顯然是一個好處。

So we expect that we would have, say, a 50-50 percent of people who have access and that's a much, much stronger position compared to when we launched. Hence, the need for having the, say, the copay support programs at the time of launch. So when we look at unaided awareness, if you look at social media activity, et cetera, we think that there is a very strong case for having a good uptick when we get back and promote it in the second half of this year.

因此，我們預計我們將擁有 50-50% 的人可以訪問，與我們推出時相比，這是一個非常非常強大的位置。因此，需要在啟動時提供共付額支持計劃。因此，當我們查看獨立意識時，如果您查看社交媒體活動等，我們認為當我們在今年下半年回歸併推廣它時，有一個很好的上升趨勢。

And then the second question on Cagrisema and the amylin component. Martin?

然後是關於 Cagrisema 和糊精成分的第二個問題。馬丁?

Yes, so important to take into account that pramlintide is used primarily in type 1 diabetes, but also a little bit in type 2 diabetes, but both in combination with insulin. So events of hypoglycemia has sort of occurred on the backbone of insulin, which, in our case, does not apply neither in obesity, obviously, but certainly also not in -- when we take this into type 2 diabetes.

是的，重要的是要考慮到普蘭林肽主要用於 1 型糖尿病，但也有少量用於 2 型糖尿病，但都與胰島素聯合使用。因此，低血糖事件發生在胰島素的主幹上，在我們的例子中，這顯然不適用於肥胖症，但當然也不適用於 - 當我們將其納入 2 型糖尿病時。

So I think as with everything else, when we combine both OADs, but also injectables with insulin, we have to take care and think about both reducing the insulin dose, but obviously also monitoring more frequently. But broadly speaking, this is not applicable for Cagrisema considerations.

所以我認為與其他一切一樣，當我們將 OAD 和注射劑與胰島素結合使用時，我們必須小心並考慮減少胰島素劑量，但顯然還要更頻繁地監測。但從廣義上講，這不適用於 Cagrisema 的考慮。

Sorry, can I just add 1? So the go, no-go decision is primarily based on whether or not you get an incremental significant decline in HbA1c versus semaglutide, is that fair?

對不起，我可以加 1 嗎？因此，去，不去的決定主要是基於你是否得到 HbA1c 相對於索馬魯肽的顯著下降，這公平嗎？

That would be fair. Obviously, we always look at safety, but we are doing the Phase II study specifically to see if we can observe an efficacy on glycemic control.

那將是公平的。顯然，我們總是關注安全性，但我們正在專門進行 II 期研究，看看我們是否可以觀察到對血糖控制的功效。

Thank you, Simon.

謝謝你，西蒙。

Next up, we have a follow-up question from Sachin Jain with Bank of America.

接下來，我們有來自美國銀行的 Sachin Jain 的後續問題。

So just 2 more, if I may. So apologies, Lars, just back on the 483 given you gave a bit of color. Have you had any media fill runs yet? Or will you have data by the time of the CMD? Just to clarify there.

所以如果可以的話，再多2個。抱歉，Lars，鑑於您給了一些顏色，請回到 483。您是否進行過任何介質填充運行？或者您在 CMD 時會有數據嗎？只是為了澄清那裡。

And then secondly, just a bigger picture question as you think about sema cagri with potential in diabetes and obesity. I wonder if you could just touch on the pros and cons of branding this combo in obesity, the same as diabetes. Obviously, for semaglutides, you did it differently with different pricing. But tirzepatide is potentially coming with similar branding and similar pricing with obesity pricing, therefore, potentially at a discount to Wegovy. Just wonder if you could just talk about how you're thinking about that as you approach the sema cagri Phase III program.

其次，當您考慮具有糖尿病和肥胖症潛力的 sema cagri 時，這只是一個更大的問題。我想知道你是否可以談談在肥胖症中標記這種組合的利弊，就像糖尿病一樣。顯然，對於 semaglutides，您以不同的價格做不同的事情。但 tirzepatide 可能具有與肥胖定價相似的品牌和相似的定價，因此可能會比 Wegovy 打折。只是想知道當您接近 sema cagri 第三階段計劃時，您是否可以談談您是如何考慮的。

Okay. Thank you, Sachin. And of course, the benefit of transparency is, of course, it generates more questions. But when you ask about details like timing of media fill and stuff like that, it's too detailed for us to get into. So I'll just say, overall, we feel that we're making good progress. We buy into the plans our partners have. We feel they are quite confident in being able to execute that. So we cannot go into more details around that.

好的。謝謝你，薩欽。當然，透明度的好處當然是它會產生更多的問題。但是，當您詢問諸如媒體填充時間之類的細節時，我們無法深入了解這些細節。所以我只想說，總的來說，我們覺得我們正在取得良好的進展。我們接受合作夥伴的計劃。我們認為他們對能夠執行該任務非常有信心。因此，我們無法對此進行更多詳細說明。

On Cagrisema and obesity, obviously, there's some time before we'll see competition in the obesity space. We have picked a pricing strategy that makes sense for us. What we see is that we're actually gaining strong reimbursement and market access based on the pricing strategy we have. How that will develop in the future based on our own success in clinical development and the success of our competitors is a bit premature for us to speculate on. Right now, we can see that there's a strong demand based on the price point we have. And I think that talks to the unmet need and the level of clinical differentiation that the products have that have been brought to the market by Novo Nordisk.

顯然，在 Cagrisema 和肥胖方面，我們還需要一段時間才能看到肥胖領域的競爭。我們選擇了一種對我們有意義的定價策略。我們看到的是，根據我們擁有的定價策略，我們實際上正在獲得強大的報銷和市場准入。基於我們自己在臨床開發方面的成功和我們競爭對手的成功，未來將如何發展，我們推測還為時過早。現在，我們可以看到基於我們現有的價格點有強勁的需求。而且我認為這與諾和諾德推向市場的產品的未滿足需求和臨床差異化水平有關。

Thank you, Sachin Jain and Natalie, for hosting us today, and thank you all for your interest in Novo Nordisk. We look forward to see you hopefully at the Capital Markets Day, March 3.

感謝 Sachin Jain 和 Natalie 今天主持我們，也感謝大家對諾和諾德的關注。我們期待在 3 月 3 日的資本市場日與您相見。

Thank you very much. Goodbye.

非常感謝你。再見。