美國安進 (AMGN) 2022 Q4 法說會逐字稿

My name is Jason, and I will be the conference facilitator today for Amgen's Fourth Quarter Full Year 2022 Financial Results Conference Call. (Operator Instructions)

我叫傑森，今天我將擔任安進 2022 年第四季度全年財務業績電話會議的會議主持人。 （操作員說明）

I would now like to introduce Mr. Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may now begin.

我現在想介紹投資者關係副總裁 Arvind Sood 先生。 Sood 先生，您現在可以開始了。

Okay. Thank you, Jason. Good afternoon, everyone, and welcome to our call to discuss the results for Q4 and full year 2022. 2022 was once again a year exemplified by great execution despite some of the macro challenges. Our Chairman and CEO, Bob Bradway, will make some opening comments, followed by prepared comments from other members of our senior leadership team.

好的。謝謝你，傑森。大家下午好，歡迎來電討論第四季度和 2022 年全年的結果。儘管存在一些宏觀挑戰，2022 年再次成為執行力出色的一年。我們的董事長兼首席執行官 Bob Bradway 將發表一些開場白，然後是我們高級領導團隊其他成員的準備好的評論。

You should have received a link to our slides that we have posted. Through the course of our discussion, we will make some forward-looking statements and use non-GAAP financial measures to describe our performance. And just a reminder that actual results can vary materially.

您應該已經收到我們發布的幻燈片的鏈接。在我們的討論過程中，我們將做出一些前瞻性陳述，並使用非 GAAP 財務指標來描述我們的業績。只是提醒一下，實際結果可能會有很大差異。

So with that, I would like to turn the call over to Bob.

因此，我想將電話轉給 Bob。

Okay. Thank you, Arvind, and hello, everyone, and thank you for joining our call. We're beginning the year feeling confident about the long-term growth outlook for our business, and let me offer 5 reasons why.

好的。謝謝 Arvind，大家好，感謝您加入我們的電話會議。今年年初，我們對我們業務的長期增長前景充滿信心，讓我提供 5 個原因。

First, we have a number of innovative, volume-driven products that still have plenty of room to run, and we saw that in 2022. Repatha, Prolia and EVENITY each generated double-digit sales and volume growth in the fourth quarter and for the full year. We expect continued growth from these products in 2023 and beyond, with Repatha, in particular, helped by important new data from the FOURIER open-label extension study and new prescribing guidelines.

首先，我們有許多創新的、以銷量為導向的產品，它們仍有很大的運行空間，我們在 2022 年看到了這一點。Repatha、Prolia 和 EVENITY 在第四季度以及整整一年。我們預計這些產品在 2023 年及以後將繼續增長，尤其是 Repatha，這得益於來自 FOURIER 開放標籤擴展研究和新處方指南的重要新數據。

Otezla delivered 7% volume growth in both the fourth quarter and the full year, benefiting from a label expansion that gives us the opportunity to reach millions of new patients in the U.S. with mild to moderate psoriasis. LUMAKRAS and TEZSPIRE collectively contributed more than $450 million in full year sales, and we're pursuing additional indications for both products. We're especially pleased to see TEZSPIRE being utilized by patients across all types of severe asthma. Murdo will share more about the performance of our in-line products in a moment.

Otezla 在第四季度和全年實現了 7% 的銷量增長，這得益於標籤擴展，使我們有機會接觸到美國數百萬輕度至中度銀屑病新患者。 LUMAKRAS 和 TEZSPIRE 全年銷售額合計貢獻了超過 4.5 億美元，我們正在為這兩種產品尋求更多適應症。我們特別高興地看到 TEZSPIRE 被所有類型的嚴重哮喘患者使用。 Murdo 稍後將分享更多關於我們在線產品的性能。

Second, we moved 6 first-in-class molecules into Phase III or potentially registration-enabling trials in 2022, including Olpasiran for LP(a), rocatinlimab for atopic dermatitis, TEZSPIRE in eosinophilic esophagitis and, of course, bemarituzimab, tarlatamab and BLINCYTO in cancer.

其次，我們將 6 個一流的分子轉移到 III 期或可能在 2022 年進行註冊試驗，包括用於 LP(a) 的 Olpasiran、用於特應性皮炎的 rocatinlimab、用於嗜酸性粒細胞性食管炎的 TEZSPIRE，當然還有 bemarituzimab、tarlatamab 和 BLINCYTO在癌症中。

We've also begun enrolling patients in a Phase II trial for AMG 133. Based on early data, this molecule, with its unique mechanism of action, looks like it may have an attractive profile for the treatment of obesity. And more on our pipeline from Dave Reese in a moment.

我們還開始招募患者參加 AMG 133 的 II 期試驗。根據早期數據，這種具有獨特作用機制的分子看起來可能在治療肥胖方面具有吸引力。稍後我們會從 Dave Reese 那裡了解更多內容。

Third, we have an industry-leading biosimilars business that will contribute to our growth over time. In 2022, we delivered positive Phase III data for our biosimilar candidates to EYLEA, SOLIRIS and STELARA, positioning us to be in the first wave of these launches, which we know is critical to success.

第三，我們擁有行業領先的生物仿製藥業務，隨著時間的推移將為我們的增長做出貢獻。 2022 年，我們向 EYLEA、SOLIRIS 和 STELARA 提交了生物仿製藥候選藥物的 III 期陽性數據，使我們處於這些上市的第一波浪潮中，我們知道這對成功至關重要。

We're also less than 24 hours into the launch of AMJEVITA in the U.S. And AMJEVITA is the leading biosimilar to HUMIRA internationally. And with a 5-month lead over the next entrant, we're well positioned for success in the U.S. All told, we have 6 more biosimilar launches planned in the U.S. and markets around the world between now and the end of the decade, making this another source of long-term growth for us.

距離 AMJEVITA 在美國上市還有不到 24 小時，AMJEVITA 是國際上領先的 HUMIRA 生物仿製藥。憑藉比下一個進入者 5 個月的領先優勢，我們為在美國取得成功做好了充分準備。總而言之，從現在到本十年末，我們計劃在美國和世界各地市場再推出 6 種生物仿製藥，這使得這是我們長期增長的另一個來源。

Fourth, we've often said that we would look to licensing and acquisitions in our stated areas of strategic interest. And that's what we've done, building on our decades of experience in inflammation with 2 significant transactions that will strengthen our presence in this space. Through the acquisition of ChemoCentryx, we added TAVNEOS, a first-in-class treatment for ANCA-associated vasculitis, and we're off to a strong start there.

第四，我們經常說我們會在我們既定的戰略利益領域尋求許可和收購。這就是我們所做的，以我們數十年的炎症經驗為基礎，通過兩項重大交易加強我們在這一領域的影響力。通過收購 ChemoCentryx，我們添加了 TAVNEOS，這是一種一流的治療 ANCA 相關血管炎的藥物，我們在這方面有了一個良好的開端。

Our announced acquisition of Horizon Therapeutics will add several additional first-in-class, early-in-life cycle biologic medicines, including TEPEZZA, KRYSTEXXA and UPLIZNA, that will add to our growth profile through 2030 and beyond. We're working our way through the regulatory review processes for that deal and are confident that the deal poses no anticompetitive matters. And we have received a second request from the U.S. FTC, and we'll work with them to answer their questions while remaining optimistic that we can complete the deal in the first half of the year.

我們宣布的對 Horizon Therapeutics 的收購將增加幾個一流的、生命週期早期的生物藥物，包括 TEPEZZA 、 KRYSTEXXA 和 UPLIZNA ，這將增加我們到 2030 年及以後的增長狀況。我們正在努力完成該交易的監管審查程序，並相信該交易不會構成反競爭問題。我們已經收到美國聯邦貿易委員會的第二份請求，我們將與他們一起回答他們的問題，同時對我們可以在今年上半年完成交易保持樂觀。

Finally, we've stayed true to our capital allocation priorities, investing in our business to drive long-term growth while also returning capital to our shareholders through share repurchases and a growing dividend. You'll hear more from Peter on this shortly. And everything we achieved last year and everything we will achieve going forward is due to the hard work and commitment of our people. They're passionate about our mission to serve patients. They're clear on how their work contributes to our success, and they're ready to seize the opportunities and meet the challenges that await us. I'm grateful to all of them.

最後，我們一直堅持我們的資本配置優先事項，投資於我們的業務以推動長期增長，同時還通過股票回購和增加股息將資本返還給我們的股東。你很快就會從彼得那裡聽到更多關於這個的信息。我們去年取得的一切成就以及我們未來將取得的一切成就都歸功於我們員工的辛勤工作和承諾。他們對我們為患者服務的使命充滿熱情。他們很清楚他們的工作如何為我們的成功做出貢獻，他們已準備好抓住機遇並迎接等待我們的挑戰。我很感謝他們所有人。

I look forward to your questions a little later on, but now, let me turn the call over to Murdo.

我期待稍後您的問題，但現在，讓我把電話轉給默多。

Thanks, Bob. 2022 was another year of strong execution of our mission to bring (inaudible) products to the millions of patients around the world who suffer from gravest illness. The evolution of our portfolio continue by record sales for 16 brands for the year. We saw strong volume gains across our general medicine and hematology-oncology growth brands. Our inflammation therapeutic area expanded with the launch of TEZSPIRE and the acquisition of TAVNEOS, 2 first-in-class medicines that treat serious disease.

謝謝，鮑勃。 2022 年是我們履行使命的又一年，我們將（聽不清）產品帶給全球數百萬患有最嚴重疾病的患者。我們的產品組合繼續演變，今年 16 個品牌的銷售額創下歷史新高。我們看到我們的普通醫學和血液腫瘤學增長品牌的銷量增長強勁。隨著 TEZSPIRE 的推出和對 TAVNEOS 的收購，我們的炎症治療領域得到了擴展，這是 2 種治療嚴重疾病的一流藥物。

In addition, our announced acquisition of Horizon Therapeutics will add several important medicines to our portfolio. In total, volume growth for 2022 was 9%, with 7% growth in the U.S. and 14% growth ex U.S., as we continue to deliver on our international growth strategy. Excluding the impact of foreign exchange, full year global product sales grew 4% as our volume increases were offset by a 5% decline in net selling price. Including the 2% negative foreign exchange impact, product sales increased 2% year-over-year.

此外，我們宣布收購 Horizon Therapeutics 將為我們的產品組合增加幾種重要的藥物。總體而言，隨著我們繼續實施我們的國際增長戰略，2022 年銷量增長 9%，其中美國增長 7%，美國以外增長 14%。排除外匯影響，全年全球產品銷售額增長 4%，因為我們的銷量增長被淨售價下降 5% 所抵消。包括 2% 的負面外匯影響，產品銷售額同比增長 2%。

In the quarter, we also saw strong volume growth with a 10% increase year-on-year. Starting with our general medicine business, which includes Prolia, EVENITY, Repatha, and Aimovig, overall revenue for these 4 products grew 21% year-over-year for the fourth quarter and 18% for the full year, driven by 19% and 21% volume growth, respectively.

在本季度，我們還看到了強勁的銷量增長，同比增長 10%。從我們的普藥業務開始，包括 Prolia、EVENITY、Repatha 和 Aimovig，這 4 種產品的總收入在第四季度同比增長 21%，全年增長 18%，受 19% 和 21 % 體積增長，分別。

In bone health, Prolia sales grew 14% year-over-year for the fourth quarter, driven primarily by 11% volume growth. EVENITY, which complements Prolia in our bone portfolio, had record sales of $225 million for the quarter, driven by strong volume growth across markets. Repatha sales increased 22% year-over-year for the fourth quarter with volume growth of 31%, partially offset by lower net selling price.

在骨骼健康方面，Prolia 第四季度銷售額同比增長 14%，主要受銷量增長 11% 的推動。 EVENITY 在我們的骨骼產品組合中補充了 Prolia，在整個市場銷量強勁增長的推動下，本季度銷售額達到創紀錄的 2.25 億美元。 Repatha 第四季度銷售額同比增長 22%，銷量增長 31%，部分被較低的淨售價所抵消。

In the U.S., we generated volume growth of 32% for the fourth quarter, aided by broad adoption of Repatha by cardiologists and increasing adoption by primary care providers. We saw declining net selling prices in the U.S. as we offered higher rebates to support broad Medicare Part D and commercial patient access. Looking ahead to 2023, we expect less year-over-year U.S. price erosion than we saw in 2022.

在美國，我們第四季度的銷量增長了 32%，這得益於心髒病專家廣泛採用 Repatha 以及越來越多的初級保健提供者採用。我們看到美國的淨銷售價格下降，因為我們提供更高的回扣以支持廣泛的 Medicare D 部分和商業患者訪問。展望 2023 年，我們預計美國價格同比下滑幅度低於 2022 年。

Outside the U.S., fourth quarter sales of Repatha grew 36% year-over-year, driven by 31% volume growth. Globally, Repatha has treated over 1.5 million patients since launch. Repatha's strong prescribing history in cardiology and expanding use in the primary care setting position us well to bring Repatha to more patients globally. With the FOURIER long-term follow-up data, in addition to evolving and more aggressive treatment guidelines, there's a clear rationale that lowering LDL cholesterol as much and as early as possible with Repatha will reduce cardiovascular risk for patients around the world.

在美國以外地區，受銷量增長 31% 的推動，Repatha 第四季度銷售額同比增長 36%。在全球範圍內，Repatha 自推出以來已治療了超過 150 萬名患者。 Repatha 在心髒病學領域的強大處方歷史和在初級保健環境中不斷擴大的使用使我們能夠很好地將 Repatha 帶給全球更多患者。根據 FOURIER 長期隨訪數據，除了不斷發展和更積極的治療指南外，還有一個明確的理由，即使用 Repatha 儘早降低 LDL 膽固醇將降低世界各地患者的心血管風險。

Transitioning to our inflammation portfolio. Otezla sales decreased 2% year-over-year for the quarter and increased 2% for the full year. We saw 7% volume growth in both periods. This was offset by lower net selling price, stemming from enhancements to our co-pay and patient assistance programs to support new patients starting treatment as well as additional rebates to improve the quality of coverage.

過渡到我們的炎症產品組合。 Otezla 本季度銷售額同比下降 2%，全年增長 2%。我們在兩個時期都看到了 7% 的銷量增長。這被較低的淨售價所抵消，這是由於我們加強了共付額和患者援助計劃以支持新患者開始治療以及額外回扣以提高覆蓋質量。

During the fourth quarter, our U.S. Otezla business was impacted by new patient demand from 3 drug programs by newly launched topical and systemic competition. We expect that impact to continue in Q1 of 2023. We also expect to see the typical pattern of lower sales in the first quarter relative to subsequent quarters due primarily to the effect of insurance reverifications, co-pays and deductibles for patients. The combined effect could lead to first quarter Otezla sales being similar to or below those from Q1 of 2022.

第四季度，我們的美國 Otezla 業務受到新推出的局部和系統競爭的 3 個藥物項目的新患者需求的影響。我們預計這種影響將在 2023 年第一季度繼續。我們還預計第一季度的銷售額將低於隨後幾個季度的典型模式，這主要是由於保險重新驗證、患者共同支付和免賠額的影響。綜合影響可能導致 Otezla 第一季度的銷售額與 2022 年第一季度相似或低於該水平。

Longer term, we continue to see strong growth potential for Otezla, given its established safety profile, strong payer coverage with limited prior authorization requirements and ease of administration. Otezla remains the only approved oral systemic therapy with a broad indication and is well positioned to help the 4 million U.S. patients with mild to moderate psoriasis, 1.5 million of whom have psoriasis that cannot be optimally addressed by a topical and can benefit from a first-line systemic treatment like Otezla.

從長遠來看，我們繼續看到 Otezla 的強勁增長潛力，因為其既定的安全狀況、強大的付款人覆蓋範圍以及有限的事先授權要求和易於管理。 Otezla 仍然是唯一獲批的具有廣泛適應症的口服全身治療藥物，並且可以很好地幫助 400 萬美國輕度至中度銀屑病患者，其中 150 萬患有無法通過局部用藥最佳治療的銀屑病患者，並且可以從首次治療中獲益線全身治療像 Otezla。

ENBREL sales decreased 1% year-over-year for the fourth quarter, driven by declines in volume and net selling price, partially offset by higher year-end inventory levels. ENBREL remains an important product for patients due to its long track record of efficacy and safety.

受銷量和淨售價下降的推動，第四季度 ENBREL 銷售額同比下降 1%，但部分被年底庫存水平上升所抵消。由於其療效和安全性的長期記錄，ENBREL 仍然是患者的重要產品。

TEZSPIRE continues its strong launch with $79 million in sales in the fourth quarter and $170 million for the full year. Allergists and pulmonologists have prescribed TEZSPIRE across a broad range of patients with severe uncontrolled asthma. We're also seeing initiation of TEZSPIRE in both biologic-naive and previously treated patients.

TEZSPIRE 繼續強勁推出，第四季度銷售額為 7900 萬美元，全年銷售額為 1.7 億美元。過敏症專家和肺病專家已為大量嚴重未控制的哮喘患者開出 TEZSPIRE 處方。我們還看到 TEZSPIRE 在未接受過生物製劑治療的患者和既往接受過治療的患者中啟動。

Physicians acknowledge TEZSPIRE unique, differentiated profile and has broad potential to treat the 2.5 million patients worldwide with severe uncontrolled asthma without any phenotypic and biomarker limitations. We're now preparing for the anticipated U.S. approval of the prefilled pen in the first quarter, which will offer patients the convenient option to administer TEZSPIRE at home.

醫生們承認 TEZSPIRE 獨特、差異化的特徵，並具有廣泛的潛力來治療全球 250 萬名嚴重不受控制的哮喘患者，而沒有任何表型和生物標誌物限制。我們現在正準備在第一季度預裝筆獲得美國的預期批准，這將為患者提供在家中使用 TEZSPIRE 的便捷選擇。

Sales of TAVNEOS were $21 million in the fourth quarter. Our integration of ChemoCentryx is proceeding smoothly, confirming our belief that Amgen's deep experience in inflammation and nephrology and substantial market presence will allow us to bring TAVNEOS to more patients with ANCA-associated vasculitis.

TAVNEOS 第四季度的銷售額為 2100 萬美元。我們對 ChemoCentryx 的整合進展順利，證實了我們的信念，即安進在炎症和腎髒病學方面的豐富經驗以及大量的市場佔有率將使我們能夠將 TAVNEOS 帶給更多 ANCA 相關血管炎患者。

We're also excited about our announced acquisition of Horizon Therapeutics. Our combined portfolio, which will include TEPEZZA, KRYSTEXXA and UPLIZNA, will address serious inflammatory diseases and improve the lives of many patients. Amgen's commercial capabilities and global presence in approximately 100 markets will allow our combined team to deliver important therapies that will make a meaningful difference for more patients globally.

我們也對我們宣布收購 Horizon Therapeutics 感到興奮。我們的合併產品組合將包括 TEPEZZA 、 KRYSTEXXA 和 UPLIZNA ，將解決嚴重的炎症性疾病並改善許多患者的生活。 Amgen 在大約 100 個市場的商業能力和全球影響力將使我們的聯合團隊能夠提供重要的治療方法，從而為全球更多患者帶來有意義的改變。

Today, we announced the launch of AMJEVITA, the first U.S. biosimilar to HUMIRA, a medicine used by more than 1 million patients living with serious inflammatory diseases. With our track record of developing and manufacturing biologics and decades of experience in inflammation, Amgen is uniquely equipped to supply patients with this biosimilar medicine. AMJEVITA is the first significant U.S. biosimilar in the pharmacy benefit space, and we expect gradual uptake in the coming months as this market evolves.

今天，我們宣布推出 AMJEVITA，這是美國首個 HUMIRA 生物仿製藥，超過 100 萬患有嚴重炎症性疾病的患者使用該藥物。憑藉我們在開發和製造生物製劑方面的業績記錄以及數十年的炎症經驗，安進具備為患者提供這種生物仿製藥的獨特能力。 AMJEVITA 是藥房福利領域第一個重要的美國生物仿製藥，我們預計隨著這個市場的發展，未來幾個月將逐漸被採用。

Moving to our hematology and oncology business, which includes LUMAKRAS, KYPROLIS, XGEVA, Vectibix, Nplate and BLINCYTO. These 6 innovative products grew 14% year-over-year with 17% volume growth for the quarter. Full year sales grew 13%, driven by volume gains. KYPROLIS sales grew 14% in the fourth quarter. Nplate sales in the fourth quarter included $207 million related to a onetime order from the U.S. government. Given the strong performance of our hem/onc portfolio in 2022 and the recent positive data on both BLINCYTO and Vectibix, I look forward to the future growth potential of this portfolio.

轉向我們的血液學和腫瘤學業務，其中包括 LUMAKRAS、KYPROLIS、XGEVA、Vectibix、Nplate 和 BLINCYTO。這 6 種創新產品同比增長 14%，本季度銷量增長 17%。在銷量增長的推動下，全年銷售額增長了 13%。 KYPROLIS 銷售額在第四季度增長了 14%。 Nplate 第四季度的銷售額包括與來自美國政府的一次性訂單相關的 2.07 億美元。鑑於我們的 hem/onc 產品組合在 2022 年的強勁表現以及近期 BLINCYTO 和 Vectibix 的積極數據，我期待該產品組合未來的增長潛力。

LUMAKRAS reported $71 million in sales in the fourth quarter and $285 million for the full year. Quarter-over-quarter sales declined 5% with 12% volume growth, more than offset by a lower net selling price, driven by a $12 million unfavorable price adjustment resulting from a reimbursement approval decision in France and unfavorable changes to estimated sales deductions.

LUMAKRAS 報告第四季度銷售額為 7100 萬美元，全年銷售額為 2.85 億美元。環比銷售額下降 5%，銷量增長 12%，這被較低的淨售價所抵消，原因是法國的報銷批准決定導致 1200 萬美元的不利價格調整以及估計銷售扣除額的不利變化。

Outside the U.S., LUMAKRAS has now been approved in over 45 countries. We've launched LUMAKRAS in 30 markets and are rapidly pursuing reimbursement in the remaining countries. As we've noted before, the market for LUMAKRAS is focused on the 7,000 U.S. and 20,000 ex U.S. patients in the second-line setting. Longer term, we expect LUMAKRAS growth to come from moving into earlier lines of therapy and expanding into additional tumor types.

在美國以外，LUMAKRAS 現已在超過 45 個國家/地區獲得批准。我們已經在 30 個市場推出了 LUMAKRAS，並正在迅速尋求在其餘國家/地區的報銷。正如我們之前所指出的，LUMAKRAS 的市場集中在二線環境中的 7,000 名美國和 20,000 名非美國患者。從長遠來看，我們預計 LUMAKRAS 的增長將來自於進入早期治療線並擴展到其他腫瘤類型。

Sales of our oncology biosimilars declined 40% year-over-year for the fourth quarter and 30% for the full year, driven by lower price. While our biosimilars for MVASI and KANJINTI both hold leading shares, we expect continued net selling price deterioration and accelerating volume declines, driven by increased competition. The most recently published average selling price in the U.S. declined 38% year-over-year for MVASI and 51% for KANJINTI. Over time, we expect long-term growth in our biosimilars business to be driven by the addition of new molecules and additional launches.

受價格下降的推動，第四季度我們的腫瘤生物仿製藥銷售額同比下降 40%，全年下降 30%。雖然我們的 MVASI 和 KANJINTI 生物仿製藥都佔據領先份額，但我們預計在競爭加劇的推動下，淨售價將繼續惡化，銷量將加速下降。最近公佈的美國平均售價 MVASI 同比下降 38%，KANJINTI 同比下降 51%。隨著時間的推移，我們預計我們的生物仿製藥業務的長期增長將受到新分子的添加和更多發布的推動。

And as we start the new year, I'm inspired by the hard work of the thousands of Amgen employees around the world who wake up every day to serve our patients. Our expanding international presence and diverse portfolio of products, further strengthened by the integration of ChemoCentryx and the announced acquisition of Horizon, position us well to serve many more patients globally.

在我們開始新的一年之際，全世界成千上萬的安進員工每天醒來為我們的患者服務，他們的辛勤工作讓我深受鼓舞。我們不斷擴大的國際影響力和多樣化的產品組合，通過整合 ChemoCentryx 和宣布收購 Horizon 得到進一步加強，使我們能夠很好地為全球更多的患者提供服務。

And with that, I'll turn it to Dave.

有了這個，我會把它交給戴夫。

Thanks, Murdo. Good afternoon, everyone. For research and development, last year was one of high-quality execution and on-time delivery of results as we continued to progress our innovative pipeline. In general medicine, we strengthened our cardiovascular franchise and emerging portfolio of obesity assets, 2 areas of significant unmet need affecting millions of patients globally.

謝謝，默多。大家下午好。對於研發，隨著我們繼續推進創新管道，去年是高質量執行和按時交付成果的一年。在普通醫學方面，我們加強了我們的心血管特許經營權和新興的肥胖資產組合，這是影響全球數百萬患者的兩個重大未滿足需求領域。

Repatha, of course, is the cornerstone of these efforts. And last November at AHA, we presented FOURIER open-label extension data. These data were recognized by the American College of Cardiology expert consensus decision pathway, which indicated there appears to be no LDL cholesterol level below which benefit ceases. Additionally, LDL cholesterol recommendations were updated to reflect a reduction in target LDL levels in highest-risk patients from 70 to 55 milligrams per deciliter. This is a level that is not attainable for a large number of patients without PCSK9 inhibitor therapy.

當然，Repatha 是這些努力的基石。去年 11 月在 AHA 上，我們展示了 FOURIER 開放標籤擴展數據。這些數據得到了美國心髒病學會專家共識決策途徑的認可，這表明似乎沒有低密度脂蛋白膽固醇水平低於該水平，益處就會停止。此外，LDL 膽固醇建議已更新，以反映最高風險患者的目標 LDL 水平從每分升 70 毫克降至 55 毫克。對於沒有 PCSK9 抑製劑治療的大量患者來說，這是一個無法達到的水平。

Another molecule that we are excited about is Olpasiran. At AHA, we presented Phase II data where Olpasiran dosed 75 milligrams or higher every 12 weeks reduced Lp(a) concentrations by 95% to 100% in patients with established atherosclerotic cardiovascular disease with baseline Lp(a) levels of approximately 260 nanomoles per liter. Olpasiran appeared both safe and well tolerated in this study.

另一個令我們興奮的分子是 Olpasiran。在美國心臟協會，我們展示了 II 期數據，其中 Olpasiran 每 12 週服用 75 毫克或更高劑量，可使患有已確診的動脈粥樣硬化性心血管疾病且基線 Lp(a) 水平約為 260 納摩爾/升的患者的 Lp(a) 濃度降低 95% 至 100% .在這項研究中，Olpasiran 似乎既安全又耐受性良好。

We are encouraged by these data, particularly our dosing frequency, safety and tolerability profile and degree of Lp(a) reduction. We have initiated a Phase III outcome study and 6,000 subjects with atherosclerotic cardiovascular disease and significantly elevated Lp(a) levels of at least 200 nanomoles per liter.

我們對這些數據感到鼓舞，尤其是我們的給藥頻率、安全性和耐受性概況以及 Lp(a) 降低程度。我們已經啟動了一項 III 期結果研究，對 6,000 名患有動脈粥樣硬化性心血管疾病且 Lp(a) 水平顯著升高至至少 200 納摩爾/升的受試者進行了研究。

Now turning to obesity. In December, we presented data from a Phase I study where AMG 133 appeared safe, well-tolerated and demonstrated a 14.5% reduction in body weight at day 85 following 3 monthly subcutaneous injections. Body weight reductions were observed up to 150 days after the final AMG 133 administration. Given these favorable attributes, we are now enrolling a 570-subject Phase II study to explore AMG 133 in patients with obesity with or without diabetes and related comorbidities. The study will also investigate different dosing levels and regimens.

現在轉向肥胖。去年 12 月，我們公佈了一項 I 期研究的數據，其中 AMG 133 看起來安全、耐受性良好，並且在每月皮下注射 3 次後第 85 天時體重減輕了 14.5%。在最後一次施用 AMG 133 後長達 150 天觀察到體重減輕。鑑於這些有利的特性，我們現在正在招募一項 570 名受試者的 II 期研究，以探索 AMG 133 在伴有或不伴有糖尿病及相關合併症的肥胖患者中的作用。該研究還將調查不同的劑量水平和方案。

(technical difficulty)

（技術難度）

Attention, everyone. Sorry for the mishap here. This call will be moving over to Webex. The numbers to call for Webex is 1 (844) 992-4726. The attendee password for the call is 198048.

大家注意。很抱歉這裡發生的事故。此呼叫將轉移到 Webex。 Webex 的呼叫號碼是 1 (844) 992-4726。呼叫的與會者密碼是 198048。

(technical difficulty) Two percentage points on a year-over-year basis, down to 16.3%. For the full year, cost of sales as a percentage of product sales decreased by 0.5 percentage points, down to 15.9%. Both the quarter and full year improvements were primarily due to fewer COVID-19 antibody shipments and lower manufacturing costs, partially offset by changes in our product mix.

（技術難度）同比下降2個百分點，降至16.3%。全年，銷售成本佔產品銷售額的百分比下降了 0.5 個百分點，降至 15.9%。本季度和全年的改善主要是由於 COVID-19 抗體出貨量減少和製造成本降低，部分被我們產品組合的變化所抵消。

Non-GAAP R&D spend in the fourth quarter decreased 2% year-over-year, primarily due to higher business development activity in 2021, including our upfront payments in connection with our Generate Biomedicines and Arrakis Therapeutics collaborations, along with lower marketed product support. This was partially offset by higher support for key assets in early- and late-stage programs. However, adjusted for 2021 BD activity, Q4 2022 R&D investment increased 7% year-over-year. And for the full year, non-GAAP R&D spend declined 8% based on the same drivers of the fourth quarter. However, adjusted for BD activity, full year 2022 R&D investment increased by 5%.

第四季度非 GAAP 研發支出同比下降 2%，這主要是由於 2021 年業務發展活動增加，包括我們與 Generate Biomedicines 和 Arrakis Therapeutics 合作相關的預付款，以及市場產品支持減少。這部分被早期和後期項目中對關鍵資產的更多支持所抵消。然而，根據 2021 年 BD 活動調整後，2022 年第四季度研發投資同比增長 7%。基於與第四季度相同的驅動因素，全年非 GAAP 研發支出下降了 8%。然而，根據 BD 活動調整後，2022 年全年研發投資增加了 5%。

Q4 non-GAAP SG&A expenses increased 2% year-over-year, driven by higher marketed product support, including investments in our priority products, TEZSPIRE, EVENITY and Repatha. For the full year, SG&A expenses were unchanged year-over-year as increased investments for all priority brands were offset by productivity gains, continuous improvement and reallocation for mature brands. Non-GAAP other income and expenses were about $470 million in expense in the fourth quarter, a $250 million increase year-over-year, primarily driven by the previously mentioned gains in 2021 that we recognized from our investment in BeiGene. For the full year, non-GAAP other income and expenses were approximately $1.7 billion.

第 4 季度非 GAAP SG&A 費用同比增長 2%，這得益於更高的營銷產品支持，包括對我們的優先產品 TEZSPIRE、EVENITY 和 Repatha 的投資。全年，SG&A 費用同比保持不變，因為對所有優先品牌的投資增加被成熟品牌的生產力提高、持續改進和重新分配所抵消。第四季度非 GAAP 其他收入和支出約為 4.7 億美元，同比增長 2.5 億美元，這主要是由於前面提到的我們從對百濟神州的投資中確認的 2021 年收益所推動。全年，非 GAAP 其他收入和支出約為 17 億美元。

So now turning to the outlook for the business for 2023. Our outlook is Amgen-only on a stand-alone basis without any adjustments for the announced Horizon acquisition. It's important to remember that currently -- that current publicly available consensus estimates are derived from a combination of estimates of Amgen as a stand-alone company, along with estimates from some analysts who have already added Horizon into their estimates. So our 2023 revenue guidance is $26.0 billion to $27.2 billion, and our non-GAAP earnings per share guidance is $17.40 to $18.60 per share.

因此，現在轉向 2023 年的業務前景。我們的前景僅在獨立的基礎上是 Amgen，沒有對已宣布的 Horizon 收購進行任何調整。重要的是要記住，目前——當前公開的共識估計來自對安進作為一家獨立公司的估計，以及一些已經將 Horizon 添加到他們的估計中的分析師的估計。因此，我們 2023 年的收入指引為 260 億美元至 272 億美元，我們的非 GAAP 每股收益指引為每股 17.40 美元至 18.60 美元。

So now let me review several key points related to our guidance. For total revenue, we expect the year-over-year comparison will not include about $700 million related to several items from 2022 that we do not expect benefit from in 2023. We assume we will not generate COVID-19 antibody revenues in 2023. We also assume a lower amount of Nplate sales in 2023 compared to 2022. Recall, 2022 included a significant purchase of Nplate by the United States government in the second half of the year.

現在讓我回顧一下與我們的指南相關的幾個要點。對於總收入，我們預計同比比較將不包括與 2022 年開始的幾個項目相關的約 7 億美元，我們預計這些項目不會在 2023 年從中受益。我們假設我們不會在 2023 年產生 COVID-19 抗體收入。我們還假設 2023 年的 Nplate 銷售額低於 2022 年。回想一下，2022 年包括美國政府在下半年大量購買 Nplate。

Also several favorable changes to estimated sales deductions that occurred in 2022 and the sale of our generics business in Turkey, which closed late in 2022. For product sales, we project volume growth at a portfolio level, driven by strong growth in our priority products, TEZSPIRE, EVENITY, Repatha, Prolia and TAVNEOS. Consistent with industry trends and our recent history, we expect mid-single-digit price declines in our portfolio in 2023.

此外，2022 年預計銷售額扣除發生的一些有利變化以及我們在土耳其的仿製藥業務的出售（該業務於 2022 年底結束）。對於產品銷售，我們預計在我們的優先產品強勁增長的推動下，產品組合層面的銷量增長， TEZSPIRE、EVENITY、Repatha、Prolia 和 TAVNEOS。與行業趨勢和我們最近的歷史一致，我們預計 2023 年我們的投資組合價格將出現中等個位數的下跌。

Turning to Neulasta and our oncology biosimilars. We expect the recent trends to continue through 2023. This will likely result in full year Neulasta sales less than $700 million. Further, we expect less than $750 million in combined product sales for our oncology biosimilars, KANJINTI and MVASI. And finally, we expect product sales of less than $300 million for EPOGEN as we transition through the expiry of our contract with DaVita.

轉向 Neulasta 和我們的腫瘤生物仿製藥。我們預計最近的趨勢將持續到 2023 年。這可能導致 Neulasta 的全年銷售額低於 7 億美元。此外，我們預計我們的腫瘤生物仿製藥 KANJINTI 和 MVASI 的產品總銷售額將低於 7.5 億美元。最後，隨著我們與 DaVita 的合同到期過渡，我們預計 EPOGEN 的產品銷售額將低於 3 億美元。

For the full year, we're guiding other revenues to a range of $1.2 billion to $1.5 billion. Note that we recognized about $300 million of revenue from our COVID antibody collaboration with Lilly in 2022 that we don't anticipate repeating in 2023. So we will continue to manage our operating expenses consistent with our historical cost discipline. So even with increasing 2023 sales volumes, declining net selling prices and inflationary pressures on costs, we still project full year non-GAAP operating expenses to be flat versus 2022 as we continue our focus on driving productivity and cost efficiencies across the enterprise.

對於全年，我們將其他收入引導至 12 億至 15 億美元的範圍內。請注意，我們在 2022 年與禮來公司的 COVID 抗體合作中確認了約 3 億美元的收入，我們預計在 2023 年不會重複。因此，我們將繼續按照我們的歷史成本紀律來管理我們的運營費用。因此，即使 2023 年銷量增加、淨售價下降和成本通脹壓力，我們仍預計全年非 GAAP 運營費用與 2022 年持平，因為我們將繼續專注於提高整個企業的生產力和成本效率。

We project non-GAAP cost of sales to be in the range of 16% to 17% as a percentage of product sales. Recall that we mentioned during our Q3 earnings discussion that tax law changes enacted by Puerto Rico in June 2022 replaced the Puerto Rico Excise Tax, the PRET, in favor of an income tax. This change will increase our income tax expense beginning in 2023 while reducing our cost of sales by roughly an equivalent amount. Note, however, there will be a negative impact in 2023 of approximately $125 million related to the amount of the PRET that is currently capitalized in inventory that will be charged to cost of goods sold in the first half of 2023, with most of the charge recognized in the first quarter without a corresponding tax benefit.

我們預計非 GAAP 銷售成本佔產品銷售額的百分比在 16% 至 17% 之間。回想一下，我們在第三季度收益討論中提到，波多黎各於 2022 年 6 月頒布的稅法變更取代了波多黎各消費稅 PRET，轉而徵收所得稅。這一變化將從 2023 年開始增加我們的所得稅費用，同時將我們的銷售成本降低大致相等的數額。但是請注意，到 2023 年將產生約 1.25 億美元的負面影響，這與目前在庫存中資本化的 PRET 的數量有關，這些 PRET 將計入 2023 年上半年的銷售成本，其中大部分費用第一季度確認，沒有相應的稅收優惠。

We expect non-GAAP R&D expenses in 2023 to increase 3% to 4% year-over-year compared to our 2022 expenses as we advanced a number of the programs Dr. Reese referenced earlier. This is consistent with our first capital allocation priority to invest in the best innovation, and our operating expense discipline provides us the capital to do just that. And for non-GAAP SG&A spend, we expect 2023 amounts as a percentage of product sales to slightly decrease year-over-year, driven by productivity improvements.

我們預計 2023 年的非 GAAP 研發費用與 2022 年的費用相比將同比增長 3% 至 4%，因為我們推進了 Reese 博士之前提到的一些項目。這與我們投資最佳創新的首要資本分配優先事項一致，我們的運營支出紀律為我們提供了實現這一目標的資本。對於非 GAAP SG&A 支出，我們預計 2023 年的金額佔產品銷售額的百分比將在生產率提高的推動下同比略有下降。

These all lead to a projected non-GAAP operating margin as a percent of product sales of roughly 50% on a full year basis. We expect non-GAAP other income and expense of approximately $1.4 billion. The expected year-over-year improvement is driven by a change in our accounting for our BeiGene investment we are making in 2023. Beginning in January 2023, we'll no longer record our share of BeiGene results in other income and expense under the equity method of accounting on our non-GAAP income statement. We'll now mark to market our investment with the impact recorded only on our GAAP income statement.

這些都導致預計全年非 GAAP 營業利潤率佔產品銷售額的大約 50%。我們預計非 GAAP 其他收入和支出約為 14 億美元。預期的同比改善是由於我們對 2023 年對北基因投資的會計處理髮生了變化。從 2023 年 1 月開始，我們將不再將我們在北基因結果中的份額記錄在股權項下的其他收入和支出中我們的非 GAAP 損益表的會計方法。我們現在將按市值計價我們的投資，其影響僅記錄在我們的 GAAP 損益表中。

We expect a non-GAAP tax rate of 18% to 19%. This rate reflects the new Puerto Rico income tax, which, as I explained earlier, replaced the PRET beginning in 2023. We expect share repurchases not to exceed $500 million in 2023, and we expect that we will continue to meaningfully increase our dividend. We expect capital expenditures of approximately $925 million in 2023, consistent with our capital allocation priority to invest in our business, including in our new environmentally friendly facilities in Ohio, North Carolina. And after we complete those facilities, we expect our capital expenditures to return to their historical levels.

我們預計非 GAAP 稅率為 18% 至 19%。這一比率反映了新的波多黎各所得稅，正如我之前解釋的那樣，它從 2023 年開始取代了 PRET。我們預計 2023 年股票回購不會超過 5 億美元，我們預計我們將繼續有意義地增加股息。我們預計 2023 年的資本支出約為 9.25 億美元，這與我們投資業務的資本分配優先順序一致，包括我們在北卡羅來納州俄亥俄州的新環保設施。在我們完成這些設施後，我們預計我們的資本支出將恢復到歷史水平。

I'd also like to make some specific comments around the first quarter of 2023. I'm encouraged that our business is performing as expected through the first month of the year. However, consistent with our historical revenue patterns, we expect revenue in the first quarter of the year to be the lowest revenue quarter of the year and slightly below revenue in Q1 2022. At a portfolio level, we expect product sales to be unchanged from Q1 2022, and other revenues to be lower on a year-over-year basis due to the reasons set out above, including about $225 million related to COVID antibody sales in the first quarter of 2022.

我還想在 2023 年第一季度左右發表一些具體評論。令我感到鼓舞的是，我們的業務在今年第一個月的表現符合預期。然而，與我們的歷史收入模式一致，我們預計今年第一季度的收入將是全年收入最低的一個季度，略低於 2022 年第一季度的收入。在產品組合層面，我們預計產品銷售額與第一季度持平2022年，由於上述原因，其他收入將同比下降，包括2022年第一季度與 COVID 抗體銷售相關的約2.25億美元。

We anticipate about $80 million of foreign exchange headwinds in Q1 2023 compared to Q1 2022. The total of all these items creates greater than $400 million of headwinds versus the first quarter 2022. So these revenue patterns, along with the timing of expenses, are expected to translate into our Q1 non-GAAP operating margin being below 50% as a percentage of product sales, although we continue to expect operating margin as a percentage of product sales to be roughly 50% for all of 2023. Recall, this is all Amgen stand-alone. We will continue to focus on our legacy of execution excellence.

與 2022 年第一季度相比，我們預計 2023 年第一季度的外匯逆風約為 8000 萬美元。與 2022 年第一季度相比，所有這些項目的總計造成了超過 4 億美元的逆風。因此，預計這些收入模式以及支出的時間安排轉化為我們的第一季度非 GAAP 營業利潤率佔產品銷售額的百分比低於 50%，儘管我們繼續預計 2023 年全年營業利潤率佔產品銷售額的百分比約為 50%。回想一下，這就是安進獨立的。我們將繼續專注於我們卓越執行的傳統。

In summary, despite macroeconomic headwinds, we delivered another strong year of financial results in 2022, keeping us on track with our long-term commitments to deliver through 2030 and beyond. Our confidence in the long-term growth of Amgen is strong, and we look forward to completing the announced acquisition of Horizon during the first half of 2023, which will only strengthen our growth prospects. We would expect to provide updated guidance, as appropriate, at some point after the transaction closes.

總而言之，儘管宏觀經濟逆風，我們在 2022 年又取得了強勁的財務業績，使我們能夠兌現到 2030 年及以後的長期承諾。我們對安進的長期增長充滿信心，我們期待在 2023 年上半年完成已宣布的對 Horizon 的收購，這只會加強我們的增長前景。我們希望在交易結束後的某個時候酌情提供更新的指南。

This concludes the financial update. My thanks to our 25,000-plus colleagues at Amgen around the world for their commitment to serving patients and their tireless efforts in 2022.

財務更新到此結束。我要感謝我們安進在世界各地的 25,000 多名同事，他們致力於為患者服務，並在 2022 年做出不懈努力。

I'll now turn it back over to Bob for our Q&A.

我現在將其轉回給 Bob 進行問答。

Okay. Well, thank you, Peter and Dave, for soldiering on despite the technical difficulties. And again, apologies to all of you who've dialed in to join us on the call and who found some disruption in the proceedings here.

好的。好吧，謝謝你們，彼得和戴夫，儘管遇到了技術困難，但還是堅持了下來。再次，向撥入電話加入我們的所有人以及發現這裡的程序受到干擾的所有人表示歉意。

A number of you have e-mailed your questions to Arvind. What I'd like to suggest is that any of you who have questions, directly e-mail them now to Arvind, and Arvind will read them. And we'll try to answer them here in the room. And let me just assure all of you that we will rearrange our schedule and be available to answer questions if we don't get to it on this conference call, be available to Arvind and his team to answer questions you may have after we wrap up.

你們中的許多人已經通過電子郵件將您的問題發送給 Arvind。我想建議的是，如果你們中的任何人有任何問題，請立即將其通過電子郵件發送給 Arvind，Arvind 會閱讀它們。我們會盡量在房間裡回答他們。讓我向你們所有人保證，我們將重新安排我們的日程安排，如果我們沒有在本次電話會議上討論，可以回答問題，在我們結束後，Arvind 和他的團隊可以回答你們可能遇到的問題.

So with that, let me turn to Arvind, and we'll tackle the questions that you've already submitted.

因此，讓我轉向 Arvind，我們將解決您已經提交的問題。

Yes. Thanks, Bob. And apologies to everybody for the technical difficulties that we have had. And as Bob said, just please e-mail your questions to me directly.

是的。謝謝，鮑勃。並為我們遇到的技術困難向大家道歉。正如 Bob 所說，請將您的問題直接通過電子郵件發送給我。

So the first question that we have is from Yaron Werber of Cowen, and he submitted 2 questions. His first question is that Amgen will move to fair value from equity method of accounting for BeiGene. As you also now own less than 19.9% equity in BeiGene, will Amgen stop consolidating BeiGene's losses and profits from now on? And then the second question is, can you discuss when you plan to file the high concentration of AMJEVITA once you get the Phase III interchangeable data in the first half of 2023?

所以我們的第一個問題來自 Cowen 的 Yaron Werber，他提交了 2 個問題。他的第一個問題是，安進將把百濟神州的權益法從權益法轉向公允價值核算。你現在持有北基因不到19.9%的股權，安進會不會從現在開始停止合併北基因的損益？然後第二個問題，2023年上半年拿到III期可互換數據後，你們打算什麼時候申報高濃度的AMJEVITA？

Okay. We do that in 2 pieces. Pete, why don't you hit the accounting question?

好的。我們分兩部分來做。皮特，你為什麼不問會計問題呢？

Yes, quick question -- quick answer. Thank you, Yaron, for the question. On BeiGene equity method of accounting, as I said in my remarks, we will record, in our GAAP income statement, the mark-to-market, but that won't be recorded in our non-GAAP income statement. So the answer is we will not include any earnings from -- or losses as our share of BeiGene going forward in our non-GAAP income statement.

是的，快速提問——快速回答。謝謝 Yaron 的提問。關於北基因權益會計法，正如我在發言中所說，我們將在我們的 GAAP 損益表中記錄按市值計價，但不會記錄在我們的非 GAAP 損益表中。所以答案是我們不會在我們的非 GAAP 損益表中包括任何收益或損失，因為我們在 BeiGene 的份額。

Okay. And then on AMJEVITA, why don't we do a 2-parter there? Dave Reese and then Murdo, you may want to add some thoughts.

好的。然後在 AMJEVITA 上，我們為什麼不在那裡進行 2 人合作呢？ Dave Reese 和 Murdo，你們可能想補充一些想法。

Yes. In terms of the filing time lines, once we have the data in hand, we'll be then giving guidance as to when we expect filing and potential approval of that after the appropriate regulatory interactions. It's important, I think, as Bob Bradway put this in context, let me ask Murdo to comment here.

是的。就備案時間表而言，一旦我們掌握了數據，我們就會在適當的監管互動後就我們預計何時備案和可能批准該文件提供指導。重要的是，我認為，正如 Bob Bradway 所說的那樣，讓我請 Murdo 在這裡發表評論。

Yes. Thanks, Dave. We have had some inbound questions on this, as you can imagine, during the day, given that we are launching. So far, launch is progressing well. We have product making its way into the channel, and we're already receiving inbound interest in AMJEVITA from payers, prescribers and patients.

是的。謝謝，戴夫。正如您想像的那樣，鑑於我們正在發布，我們在白天收到了一些關於此的入站問題。到目前為止，發射進展順利。我們的產品正在進入渠道，我們已經收到付款人、開處方者和患者對 AMJEVITA 的入境興趣。

One thing that's important to remember is the current product that we have in the market is a lower concentration, original concentration AMJEVITA or adalimumab, but it is citrate-free, meaning that the patient experience here is still one where we minimize the injection site pain by having a citrate-free formulation.

需要記住的一件重要事情是，我們目前在市場上擁有的產品是濃度較低的原始濃度 AMJEVITA 或阿達木單抗，但它不含檸檬酸鹽，這意味著這裡的患者體驗仍然是我們將注射部位疼痛降至最低的體驗通過使用不含檸檬酸鹽的配方。

And patient experience here has been positive in our clinical trials, and we anticipate that not having a high concentration will not be a barrier in the market. These are very low volumes that are injected through an auto-injectable pen. And we've seen very, very good reliability of patients being able to administer.

在我們的臨床試驗中，這裡的患者體驗是積極的，我們預計濃度不高不會成為市場障礙。這些是通過自動注射筆注射的非常低的體積。我們已經看到患者能夠進行非常非常好的給藥可靠性。

In addition, of course, we provide nurse support for patients. And then while it wasn't asked, I think it's also important to note that we are providing financial assistance, support and reimbursement support for both prescribers and patients as we launch the product. So really a full suite of services and support that you would expect for a branded launch being applied to the launch of the first biosimilar, adalimumab, to launch in the U.S., that is AMJEVITA.

此外，當然，我們還為患者提供護士支持。然後雖然沒有被問到，但我認為同樣重要的是要注意我們在推出該產品時為處方者和患者提供經濟援助、支持和報銷支持。因此，真正的一整套服務和支持，您期望品牌發布應用於第一個生物仿製藥阿達木單抗的發布，該生物仿製藥將在美國推出，即 AMJEVITA。

Okay. Thank you, Murdo and Dave. Let's go to the next question, Arvind.

好的。謝謝默多和戴夫。讓我們轉到下一個問題，Arvind。

So the next question is from Geoff Meacham from BofA Merrill Lynch. And his question is, he said, I know you have AMJEVITA but are you expecting an indirect impact in the second half of '23 or the first half of '24 from all the HUMIRA biosimilars and STELARA, on Otezla and ENBREL mainly? And he is interested in the volume and price impact.

所以下一個問題來自美銀美林的 Geoff Meacham。他的問題是，他說，我知道你有 AMJEVITA，但你是否預計所有 HUMIRA 生物仿製藥和 STELARA 在 23 年下半年或 24 年上半年主要對 Otezla 和 ENBREL 產生間接影響？他對數量和價格的影響很感興趣。

Okay. Murdo, you want to share your thoughts on that?

好的。 Murdo，你想分享你的想法嗎？

It's hard for me, obviously, to comment on what competitors may do as other biosimilars of adalimumab enter the market beyond July. But what we have seen coming into 2023 is a good cycle of reimbursement negotiations, and we've been able to secure a very broad coverage for both ENBREL and Otezla. We expect that insurance coverage to continue throughout the course of 2023. And as is usual, we had small concessions on net price to secure that broad reimbursement, but nothing unusual compared to prior years.

顯然，隨著其他阿達木單抗生物仿製藥在 7 月之後進入市場，我很難評論競爭對手可能採取的行動。但我們看到進入 2023 年的是一個良好的報銷談判週期，我們已經能夠確保 ENBREL 和 Otezla 的覆蓋範圍非常廣泛。我們預計保險範圍將持續到 2023 年。和往常一樣，我們在淨價上做出了小幅讓步以確保獲得廣泛的報銷，但與往年相比沒有什麼不尋常的。

Thank you. Let's go to the next question.

謝謝你。讓我們進入下一個問題。

The next question is from Chris Raymond from Piper Sandler, and he has 2 questions. The first one is on Otezla. And Chris says, I know there are a lot of puts and takes on this market, and I know you guys have highlighted a tailwind of mild-to-moderate psoriasis patients coming into therapy. But Otezla is kind of unique in that there is a sizable discontinuation rate.

下一個問題來自 Piper Sandler 的 Chris Raymond，他有 2 個問題。第一個在 Otezla 上。克里斯說，我知道這個市場上有很多看跌期權，我知道你們已經強調了輕度至中度牛皮癬患者接受治療的順風。但 Otezla 有點獨特，因為停藥率很高。

Just with that, if you're probably not going away, talk about why we shouldn't be more concerned about SOTYKTU and maybe just as importantly, the next-generation TYK2 molecules that are coming behind it. Especially noticing that a decline Q-over-Q both in the U.S. and rest of the world, even with a 9% inventory build, any color on how you grow through this coming competition would be very helpful. And then he has a question on AMJEVITA.

就此而言，如果您可能不會離開，請談談為什麼我們不應該更加關注 SOTYKTU，也許同樣重要的是，它背後的下一代 TYK2 分子。特別注意到美國和世界其他地區的 Q-over-Q 下降，即使庫存增加了 9%，任何關於你如何在即將到來的競爭中成長的顏色都會非常有幫助。然後他有一個關於 AMJEVITA 的問題。

Okay. So first on Otezla, I would start with the fact that we are the only systemic product indicated for a broad range of psoriasis patients without regard to the severity, and really makes us the ideal first-line first systemic post-topical choice of therapy. And that is the positioning of the brand. The size of that market is very large. There's 4 million patients with a mild to moderate form of psoriasis. About 1.5 million of those patients would be regarded as not doing as well as they could on topical treatment by potential switching to a systemic like Otezla.

好的。因此，首先在 Otezla 上，我將從以下事實開始：我們是唯一適用於廣泛銀屑病患者（無論其嚴重程度如何）的全身性產品，這確實使我們成為理想的一線首個全身性局部後治療選擇。這就是品牌的定位。那個市場的規模非常大。有 400 萬輕度至中度牛皮癬患者。這些患者中約有 150 萬可能會轉而使用像 Otezla 這樣的全身性藥物，但他們的局部治療效果可能不如他們所能達到的那樣好。

As I mentioned just a few moments ago, Otezla also enjoys very broad frontline access, that is, it doesn't require that you step through another systemic therapy. And it also means that prescribers can make it the first choice. And these are busy dermatologists. They want something that's easy. They don't want a lot of prior paperwork. And they want to be able to provide an ability for patients to start quickly on their therapy. Only Otezla offers that in the psoriasis market.

正如我剛才提到的，Otezla 也享有非常廣泛的前線使用權，也就是說，它不需要您通過另一種全身療法。這也意味著開處方者可以將其作為首選。這些都是忙碌的皮膚科醫生。他們想要簡單的東西。他們不想要很多事先的文書工作。他們希望能夠為患者提供快速開始治療的能力。在銀屑病市場上只有 Otezla 提供這種產品。

I think what we're seeing right now is an effect of a number of free goods programs that were launched at the end of last year and continue into this quarter. When physicians have free goods programs, or sometimes referred to as bridging programs usually used at the beginning of a product launch when there hasn't been an opportunity to secure access with pharmacy benefit managers, physicians will sometimes use those to try novel therapies coming into the market.

我認為我們現在看到的是去年年底推出並持續到本季度的一些免費商品計劃的影響。當醫生有免費商品計劃，或者有時被稱為橋接計劃時，通常在產品發布之初使用，當時還沒有機會與藥房福利經理取得聯繫，醫生有時會使用這些計劃來嘗試新療法市場。

However, as those novel therapies go through the negotiation process with PBMs and payers, oftentimes, it becomes more difficult to try those novel therapies because of the nature of the access that they result with. And I think that's really where the sustained advantage of Otezla in that first-line systemic, post-topical, prebiologic patient population really allows us a long-term growth opportunity. And we continue to feel confident in the long-term growth of this brand.

然而，隨著這些新療法通過與 PBM 和付款人的談判過程，通常，嘗試這些新療法變得更加困難，因為它們所導致的訪問的性質。我認為這確實是 Otezla 在一線系統性、局部後、生物前患者群體中的持續優勢真正讓我們獲得長期增長機會的地方。我們繼續對這個品牌的長期發展充滿信心。

And we have a very strong commercial presence in a number of markets around the world, and we continue to feel good from what we're hearing from our prescribing base of dermatologists. I will say that the short-term impact of these free good programs, we're watching it very closely, and we're making sure that we continue to be competitive in the marketplace.

我們在全球許多市場都有非常強大的商業影響力，我們繼續從我們的皮膚科醫生處方基地聽到的消息中感覺良好。我要說的是，這些免費的好項目的短期影響，我們正在密切關注，我們正在確保我們繼續在市場上具有競爭力。

Okay. Chris' second question is the same as the question that we have from Salveen Richter of Goldman Sachs. And she says, on AMJEVITA, could you offer more details on how the dual-pricing option will work and drive uptick? And how should we think about net pricing? What are your expectations for the market in midyear once more biosimilars enter?

好的。 Chris 的第二個問題與高盛的 Salveen Richter 提出的問題相同。她說，在 AMJEVITA 上，你能否提供更多關於雙重定價選項如何運作和推動價格上漲的細節？我們應該如何考慮淨定價？生物仿製藥再次進入市場，您對年中市場有何期待？

Well, maybe I can answer the second part first. We don't comment on product-specific pricing, and so I really can't answer the net price. I think it's fair to say that as additional entrants come into the market, net prices usually go down, and we've seen that in our other biosimilars business, but we would expect that to happen here.

好吧，也許我可以先回答第二部分。我們不對特定產品的定價發表評論，所以我真的無法回答淨價。我認為可以公平地說，隨著更多的進入者進入市場，淨價通常會下降，我們已經在其他生物仿製藥業務中看到了這一點，但我們希望這會發生在這裡。

With respect to the 2 list price approach that we've employed here at this launch, this is really to address the complexity of the U.S. market. Pharmacy benefit managers have a business model that requires that they negotiate rebates with manufacturers, and so they would prefer a high list price and negotiate rebates to net the price down and then pass those rebates through to their upstream employer clients.

關於我們在本次發布會上採用的 2 標價方法，這實際上是為了解決美國市場的複雜性。藥品福利經理的商業模式要求他們與製造商協商回扣，因此他們更喜歡高標價並協商回扣以壓低價格，然後將這些回扣傳遞給上游雇主客戶。

There are other stakeholders and customers in the health care system that prefer a net price-based model and don't care about the difference between list and net or gross price and net price. And so for those, we have the lower net price product available. So just a reminder, we have a high list price at 5% below HUMIRA, and then we have a low list price at 55% below HUMIRA.

醫療保健系統中還有其他利益相關者和客戶更喜歡基於淨價的模型，並不關心標價與淨價或總價與淨價之間的差異。因此，對於那些，我們提供了較低淨價的產品。所以提醒一下，我們有一個比 HUMIRA 低 5% 的高標價，然後我們有一個比 HUMIRA 低 55% 的低標價。

We also intend to ensure that AMJEVITA is an affordable medicine for patients by providing co-pay assistance as well as helping patients secure reimbursement through the insurer. We are also pleased to report that we enjoy broad access out of the gate on day 1 of launch with the 3 national pharmacy benefit managers, so broad parity coverage alongside HUMIRA.

我們還打算通過提供共同支付援助以及幫助患者通過保險公司獲得報銷，確保 AMJEVITA 成為患者負擔得起的藥物。我們也很高興地報告，我們在推出的第一天就享有與 3 位國家藥房福利經理的廣泛接觸，因此與 HUMIRA 一樣廣泛的平價覆蓋。

Let me just -- I note that we're up to the half past the hour, but we will continue to take questions for as long as necessary here to answer those questions and until there is a recording of this that will be available in the form of a transcript for those of you that have conflicts and can't stay beyond the set time. So Arvind, why don't you go to the next question?

讓我 - 我注意到我們已經到了半點半，但我們將繼續回答問題，只要有必要，就可以在這裡回答這些問題，直到有錄音可以在對於那些有衝突並且不能超過規定時間的人的成績單形式。那麼 Arvind，你為什麼不轉到下一個問題？

Yes. The next question is from Colin Bristow for UBS. And here's a question on the obesity pipeline. What update should we expect to get this year? Will we see data from the remaining 3 cohorts from the Phase I study? And then on AMG 786, when should we expect updates, more disclosure on this asset and program?

是的。下一個問題來自瑞銀的 Colin Bristow。這是關於肥胖管道的問題。今年我們應該期待什麼更新？我們會看到來自 I 期研究的其餘 3 個隊列的數據嗎？然後在 AMG 786 上，我們應該什麼時候期待更新，關於這個資產和程序的更多披露？

Yes. In terms of the obesity pipeline, AMG 133, the 2 additional cohorts you're referring to, I don't know that we'll see data over the course of this year on that. If that changes, of course, I'll provide guidance. AMG 786 is a small molecule with a different mechanism of action, as indicated to GLP-1 or GIPR receptor agonist or antagonist. So that's going through dose escalation over the course of the year. I'll provide guidance in terms of when we may see data from that program. And of course, at the time of data availability, we'll talk about the target as well.

是的。關於肥胖管道，AMG 133，你提到的另外兩個隊列，我不知道我們會在今年的過程中看到這方面的數據。如果情況發生變化，我當然會提供指導。 AMG 786 是一種小分子，具有與 GLP-1 或 GIPR 受體激動劑或拮抗劑不同的作用機制。因此，在這一年中，劑量會逐漸增加。我將就何時可以看到該程序的數據提供指導。當然，在數據可用時，我們也會討論目標。

Okay. Thanks, David. Arvind, let's go to the next question.

好的。謝謝，大衛。 Arvind，讓我們進入下一個問題。

So the next question is from Evan Seigerman from BMO Capital Markets. And Evan wanted to know, he said, with slowing LUMAKRAS sales, can you expand on how you may have revised your commercial strategy to better align with the commercial potential of the assets?

所以下一個問題來自 BMO Capital Markets 的 Evan Seigerman。 Evan 想知道，他說，隨著 LUMAKRAS 銷售放緩，您能否詳細說明您可能如何修改您的商業戰略以更好地與資產的商業潛力保持一致？

Yes. I'm not sure we have a slowing overall volume growth. I think what we saw, and I mentioned this, it might not have come through clearly on the audio, but in the quarter, we did see a price effect based on reaching reimbursement decision finalization in France. And so we had a $12 million charge in the quarter against LUMAKRAS. It grew 7% volume in the quarter. But I think we anticipated the opportunity for LUMAKRAS in second-line being limited to the incident population. And we are commercially and medically sized appropriately for that opportunity. I think as we expand into earlier lines of therapy or other tumor types, we will continue to invest behind the product.

是的。我不確定我們的整體銷量增長是否放緩。我認為我們所看到的，我提到過這一點，它可能沒有在音頻中清楚地體現出來，但在本季度，我們確實看到了基於在法國達成報銷決定最終確定的價格效應。因此，我們在本季度對 LUMAKRAS 收取了 1200 萬美元的費用。它在本季度增長了 7%。但我認為我們預計 LUMAKRAS 在二線的機會僅限於事件人群。我們的商業和醫療規模適合這個機會。我認為，隨著我們擴展到早期治療線或其他腫瘤類型，我們將繼續投資該產品。

Okay. The next question is from Michael Yee. And Michael wants to know, he said, on 2023 guidance, can you clarify what the input is for revenue growth versus EPS growth range? Specifically, is there a positive impact from BeiGene accounting? And does the tax rate of 18% to 19% negatively impact EPS? Or is COGS offset, as explained last year, is 2023 OpEx growing more than revenue?

好的。下一個問題來自 Michael Yee。 Michael 想知道，他說，關於 2023 年的指導，你能否澄清收入增長與 EPS 增長范圍的輸入是什麼？具體來說，北基因會計是否有積極影響？ 18% 到 19% 的稅率是否會對每股收益產生負面影響？還是如去年所解釋的那樣，COGS 抵消了 2023 年 OpEx 的增長是否超過了收入？

Let me start by working our way from the tax question. So on the tax side of it, the 18% to 19% is increases by the PRET amount. Although, as I have highlighted both last year and this year, we have a small carryover effect of about $125 million that's currently capitalized in cost of goods sold that will be released that -- excuse me, currently capitalized in inventory that will be released in the cost of goods sold, primarily during the first quarter, without a corresponding tax benefit. So the answer is, going forward, after that $125 million works its way through cost of goods sold, it will be roughly equivalent to move from the Puerto Rico Excise Tax or the PRET, which was recorded in cost of goods sold, down to the actual income tax rate.

讓我從稅收問題開始。所以在稅收方面，18% 到 19% 是按 PRET 金額增加的。雖然，正如我在去年和今年都強調的那樣，我們有大約 1.25 億美元的小結轉效應，目前資本化為將釋放的已售商品成本 - 對不起，目前資本化為將在銷售商品的成本，主要是在第一季度，沒有相應的稅收優惠。所以答案是，展望未來，在這 1.25 億美元通過銷售商品成本後，它大致相當於從記錄在銷售商品成本中的波多黎各消費稅或 PRET 轉移到實際所得稅率。

The question on guidance. And I think the question was, what's included from BeiGene and what's not. As I said earlier to Yaron's question, what won't be included now is our share of either losses or gains in BeiGene's income. So we will include, on a mark-to-market basis in our GAAP income statement, the results of BeiGene and then the movements in the security but not in our non-GAAP income statement. We will no longer record our share of their losses or their income.

關於指導的問題。我認為問題是，百濟神州包含什麼，不包含什麼。正如我之前對 Yaron 的問題所說，現在不包括的是我們在百濟神州收入中的損失或收益份額。因此，我們將在我們的 GAAP 損益表中按市值計價，包括百濟神州的業績，然後是證券的變動，但不包括在我們的非 GAAP 損益表中。我們將不再記錄我們在他們的損失或收入中的份額。

Let me just say, Michael, and to the prior question from Evan, if you need more detail on that to make sure you fully understand what we're saying in our response, just let us know, we'll get back to you. I think, particularly, Evan, for your question, if you're not familiar with that mechanism, that's common to us in France. Happy just to provide more color for you. And again, Michael, I know a lot going on here, and apologies for the disruption and don't know if you were able to follow all the slides earlier. So if you need more color, let us know, we'll call you back after the conference call. Okay. Go ahead, Arvind, to the next question.

我只想說，邁克爾，對於 Evan 之前的問題，如果你需要更多詳細信息以確保你完全理解我們在回復中所說的內容，請告訴我們，我們會盡快回复你。我認為，特別是埃文，對於你的問題，如果你不熟悉這種機制，那在我們法國很常見。快樂只為為您提供更多色彩。再說一次，邁克爾，我知道這裡發生了很多事情，對於打擾我深表歉意，不知道你是否能夠早先觀看所有幻燈片。因此，如果您需要更多顏色，請告訴我們，我們會在電話會議後給您回電。好的。繼續，Arvind，下一個問題。

Okay. Then we have a second question from Salveen asking, could you put the upcoming TEPEZZA Phase IV data and chronic context for us? What do you need to see? How would positive data expand the opportunity for the drug?

好的。然後我們有來自 Salveen 的第二個問題，你能為我們提供即將到來的 TEPEZZA IV 期數據和慢性背景嗎？你需要看什麼？積極的數據將如何擴大藥物的機會？

We are subject to the restrictions that we have on our ability to say anything on what's in the documents. You want to address that?

我們受到限制，我們無法就文件中的內容髮表任何意見。你想解決這個問題嗎？

Yes. I mean, I think we're restricted, of course, by Irish takeover rules here. What we can say is that it's worth reminding everyone that the current label is broad and encompasses patients with thyroid eye disease, the -- due to autoimmune thyroiditis. This is primarily a study that will generate data in a population that we believe will help with reimbursement and with payers. And let me ask Murdo to comment on that.

是的。我的意思是，我認為我們當然受到愛爾蘭收購規則的限制。我們可以說的是，值得提醒大家的是，目前的標籤範圍很廣，包括患有甲狀腺眼病的患者——由於自身免疫性甲狀腺炎。這主要是一項研究，將在我們認為將有助於報銷和付款人的人群中生成數據。讓我請默多對此發表評論。

I would point out that mechanistically, there is no difference between chronic thyroid eye disease and the acute form of the disease. In fact, it's a semantic definition as to when the disease progresses to the chronic form. But the underlying pathogenic mechanism of being driven in large part by IGF1R is intact. And therefore, based on prior data and mechanistically, we're optimistic about that study. Murdo?

我要指出的是，從機制上講，慢性甲狀腺眼病和該病的急性形式之間沒有區別。事實上，這是關於疾病何時發展為慢性形式的語義定義。但在很大程度上由 IGF1R 驅動的潛在致病機制是完整的。因此，根據先前的數據和機制，我們對這項研究持樂觀態度。默多？

Yes. Look, I think the Horizon team is doing a very good job commercializing this product and continue to help many patients within the broad current indication, as Dave mentioned. And I think additional data here could be additive to the already very promising growth of the product.

是的。看，我認為 Horizon 團隊在將該產品商業化方面做得非常好，並繼續在廣泛的當前適應症範圍內幫助許多患者，正如 Dave 提到的那樣。而且我認為這裡的額外數據可能會增加產品已經非常有希望的增長。

Okay. Thanks, Salveen, for your question. Let's go to the next one, Arvind.

好的。謝謝，Salveen，你的問題。讓我們轉到下一個，Arvind。

The next one is from Christopher Schott of JPMorgan. And Christopher is saying, can you elaborate on our Otezla in 2023? Bristol is suggesting that they are seeing some strong initial uptake in their bridge program and would be interested how much of this market expansion for orals versus something you're seeing in Otezla? And you mentioned an impact from competitor-free drug impact over the next few quarters. Do you anticipate that will lessen as the year continues or an impact for much of the year?

下一個來自摩根大通的克里斯托弗肖特。克里斯托弗說，你能詳細說明我們 2023 年的 Otezla 嗎？ Bristol 表示，他們在橋接計劃中看到了一些強勁的初步吸收，並且很想知道這種口語市場擴張與您在 Otezla 中看到的市場擴張有多大？你提到了未來幾個季度無競爭對手藥物影響的影響。您是否預計隨著今年的繼續或一年中大部分時間的影響會減少？

Yes. It's a similar question to one asked earlier, but perhaps I can elaborate a little bit for Chris. It's fairly clear that dermatologists want to use the easiest product and safest and well-understood product when moving to a first systemic treatment post topically. Many of these topical patients are hesitant to try a systemic agent. And so I think this is where Otezla's profile studied extensively with over 700,000 patients globally having experienced this product, the safety and efficacy of Otezla is extremely well understood.

是的。這是一個與之前提出的問題類似的問題，但也許我可以為 Chris 詳細說明一下。很明顯，皮膚科醫生希望在局部進行第一個全身治療後使用最簡單、最安全和最容易理解的產品。這些局部患者中的許多人對嘗試全身性藥物猶豫不決。因此，我認為這是對 Otezla 的概況進行廣泛研究的地方，全球有超過 700,000 名患者體驗過該產品，Otezla 的安全性和有效性廣為人知。

As I mentioned earlier, the frontline access coverage that we've secured in the U.S. without a lot of prior authorization requirement, the convenience of that for dermatology practices is very clear. And it makes it a really good first-line treatment, systemic treatment, especially for a patient with milder or more moderate disease. For moderate or severe disease, it is likely that you're going to need to use something like a biologic or a second-line agent.

正如我之前提到的，我們在美國獲得的前線訪問覆蓋範圍沒有很多事先授權要求，這對皮膚科實踐的便利性非常明顯。它使它成為一種非常好的一線治療、全身治療，特別是對於患有輕度或中度疾病的患者。對於中度或重度疾病，您可能需要使用生物製劑或二線藥物。

And we think that given that SOTYKTU has yet to go through the market access process and secure payer reimbursement, we're not really seeing how it's actually going to be used longer term in the marketplace. And I think sometimes, these pretty good programs can distort what the actual uptake curve will be for a product.

我們認為，鑑於 SOTYKTU 尚未通過市場准入流程和安全的付款人報銷，我們還沒有真正看到它在市場上的長期使用情況。而且我認為有時候，這些非常好的程序可能會扭曲產品的實際吸收曲線。

Then Murdo, there is a second question from Chris. He's asking, how are you thinking about ENBREL pricing dynamics over time, given the expected significant price declines in the HUMIRA market. I know you've talked about price continuing to erode but not accelerate. Can you remind us why we shouldn't expect a bigger step-down in price in 2023 or 2024 as the HUMIRA market price resets down significantly?

然後是 Murdo，Chris 有第二個問題。他問，鑑於 HUMIRA 市場預期的價格大幅下跌，您如何看待 ENBREL 隨時間推移的定價動態。我知道你談到價格繼續下跌但沒有加速。您能否提醒我們，為什麼我們不應該期望在 2023 年或 2024 年隨著 HUMIRA 市場價格大幅下調而出現更大的降價？

Well, as I mentioned before, we're primarily through our 2023 cycle and we've secured very good access. We've had to concede a bit of price, as I mentioned, but not anything that looks precipitous compared to prior years. So we're pleased with that. ENBREL is an important product for many indications.

好吧，正如我之前提到的，我們主要是通過 2023 年的周期，並且我們已經確保了非常好的訪問權限。正如我所提到的，我們不得不讓步一些價格，但與前幾年相比，沒有任何看起來很陡峭的東西。所以我們對此感到滿意。 ENBREL 是許多適應症的重要產品。

We see that the safety and efficacy profile of ENBREL is well understood. I think physicians also want choice. And I think that's where PBMs are also open to having more than one TNF product on their formulary. And I think that's really what we've been able to secure and what we continue to think we'll be able to achieve in the future.

我們看到 ENBREL 的安全性和有效性概況已廣為人知。我認為醫生也需要選擇。我認為這就是 PBM 也願意在他們的處方集上擁有不止一種 TNF 產品的地方。而且我認為這確實是我們能夠確保的，也是我們認為未來能夠實現的。

Let's go to the next question.

讓我們進入下一個問題。

The next question is from Mohit Bansal from Wells Fargo. And his question is, could you talk a little bit more about your HUMIRA biosimilar negotiations thus far? Seems like AbbVie has parity access with majority of them and the pricing is different for the first half versus the second half and there's more competition. Are your contracts similar? And how should we think about the cadence of launch as the year progresses?

下一個問題來自富國銀行的 Mohit Bansal。他的問題是，你能多談談到目前為止你的 HUMIRA 生物仿製藥談判嗎？似乎艾伯維（AbbVie）與他們中的大多數人都有同等的訪問權，而且上半年和下半年的定價不同，而且競爭更加激烈。你們的合同相似嗎？隨著時間的推移，我們應該如何考慮發布的節奏？

Well, I can't comment on a competitor's contracts with PBMs or payers. What I can say is we've secured broad access for AMJEVITA at the 3 national PBMs. We continue to work with other customers to provide access for providers and patients alike. And we'll continue to compete effectively as we have done everywhere else in the world with this product. And outside of the U.S., we were able to establish a leadership position with AMGEVITA. And we think, given the services that we've provided and the commercial footprint we have, we're in a very good competitive position vis-à-vis other biosimilars.

好吧，我不能評論競爭對手與 PBM 或付款人的合同。我可以說的是，我們已經確保 AMJEVITA 在 3 個國家 PBM 中的廣泛使用。我們繼續與其他客戶合作，為提供者和患者提供訪問權限。我們將繼續有效競爭，就像我們將在世界其他任何地方使用該產品所做的那樣。在美國之外，我們能夠通過 AMGEVITA 確立領導地位。我們認為，鑑於我們提供的服務和我們擁有的商業足跡，與其他生物仿製藥相比，我們處於非常有利的競爭地位。

I know a number of you have submitted questions, so we're continuing to work through the list. Anybody who hasn't yet shot Arvind an e-mail, we're going to go through those and we've got couple of handfuls still to go. So let's, Arvind, go to the next question.

我知道你們中的許多人都提交了問題，因此我們將繼續處理該列表。任何還沒有給 Arvind 發送電子郵件的人，我們將通過這些，我們還有幾把要處理。那麼，Arvind，讓我們轉到下一個問題。

Yes. The next 1 is a question by Greg Renza of RBC Capital Markets, and Dave, this is for you. We were interested in hearing some color on the antibody drug conjugate strategy in light of the recent deals. How is the team approaching the space?

是的。下一個是 RBC Capital Markets 的 Greg Renza 和 Dave 的問題，這是給你的。鑑於最近的交易，我們有興趣聽到抗體藥物偶聯策略的一些顏色。團隊是如何接近這個空間的？

Yes. Thanks, Greg. What I view this at is as another modality in our toolkit. We've been watching the antibody drug conjugate technology quite closely for the past several years. It's advanced, so what we feel is that we'll use ADCs on appropriate targets. I view it as an addition and an extension of our modalities.

是的。謝謝，格雷格。我認為這是我們工具包中的另一種形式。在過去的幾年裡，我們一直在密切關注抗體藥物偶聯技術。它很先進，所以我們覺得我們將在適當的目標上使用 ADC。我將其視為我們模式的補充和延伸。

These collaborations bring together our experience on target identification and validation as well as, of course, antibody generation with some of the newer conjugation technology. So as that progresses, more to come, but you should view this as additive to our armamentarium.

這些合作匯集了我們在目標識別和驗證方面的經驗，當然還有使用一些較新的偶聯技術生成抗體的經驗。因此，隨著進展，還會有更多，但您應該將其視為對我們軍備庫的補充。

Okay. The next question is by Tim Anderson of Wolfe Research. And his question is on AMJEVITA in the U.S. And he's asking, any commentary and your comfort with sell-side consensus for U.S. sales, which seems to be around $600 million in 2023? And anything you can say about contract specifics such as whether there's price protection, if any of them go beyond 2023?

好的。下一個問題由 Wolfe Research 的 Tim Anderson 提出。他的問題是關於美國的 AMJEVITA。他問的是，任何評論和您對美國銷售的賣方共識是否滿意，2023 年美國銷售額似乎約為 6 億美元？關於合同細節，你有什麼可以說的嗎，比如是否有價格保護，如果其中任何一個超過 2023 年？

Yes, we don't give product-specific guidance. And this is a new event in the U.S. biosimilar market, given this is the first big pharmacy benefit product to go up. So we will continue to update all of you as the launch progresses. We have said we think this will be gradually slope on this launch, and I'm going have to keep you apprised as we go forward.

是的，我們不提供特定於產品的指導。這是美國生物仿製藥市場的新事件，因為這是第一個上市的大型藥房福利產品。因此，隨著發布的進行，我們將繼續為大家更新。我們已經說過，我們認為這將在這次發布中逐漸傾斜，我將不得不在我們前進的過程中隨時通知您。

Okay. The next one is by Dave Risinger of SVB Securities, and he has 2 questions. The first one is for you, Dave. Please discuss key novel drug candidate readouts to watch in 2023. And the second one for you, Murdo. How do you expect formulary positioning for AMJEVITA to potentially change in January of 2024 after AMJEVITA is assigned an interchangeability designation?

好的。下一個是 SVB Securities 的 Dave Risinger，他有 2 個問題。第一個是給你的，戴夫。請討論 2023 年值得關注的關鍵新型候選藥物讀數。第二個是給你的，默多。在 AMJEVITA 獲得可互換性指定後，您預計 AMJEVITA 的處方定位在 2024 年 1 月可能會發生什麼變化？

Yes. Thanks, David. This is a year where, certainly, my focus, my team's focus, will be on execution, a huge amount to carry forward in the pipeline. So things that I would keep an eye on, how well are we enrolling the Phase III Olpasiran trial, how well are we enrolling the AMG 133 Phase II trial. In the general medicine portfolio, in inflammation, how are the suite of rocatinlimab trials enrolling? How are we delivering on TEZSPIRE additional indications? And then finally, in oncology, things to keep an eye on are the tarlatamab program, not only the Phase II potentially registrational trial readout in the second half of the year, but also initiation of a Phase III trial in second-line disease. These are some of the top line things that I'll be paying attention to. And then there are, of course, a host of others earlier in the pipeline and in discovery research.

是的。謝謝，大衛。這一年，當然，我的重點，我的團隊的重點，將放在執行上，這是一個巨大的過程。所以我會關注的事情，我們在 III 期 Olpasiran 試驗中的進展情況，我們在 AMG 133 II 期試驗中的進展情況。在普通藥物組合中，在炎症方面，rocatinlimab 試驗套件的招募情況如何？我們如何提供 TEZSPIRE 的額外適應症？最後，在腫瘤學方面，需要關注的是 tarlatamab 計劃，不僅是今年下半年的 II 期潛在註冊試驗讀數，而且還啟動了二線疾病的 III 期試驗。這些是我會關注的一些最重要的事情。當然，還有許多其他早期的管道和發現研究。

And just on the AMJEVITA question, I would say that we have a commitment to continuing to make sure that the product attributes of our biosimilars provide payers, providers and patients with all of the benefits that they're looking for. And we're also trying to ensure that there is no reason to switch away from AMJEVITA in the long range.

就 AMJEVITA 問題而言，我想說我們承諾繼續確保我們的生物仿製藥的產品屬性為付款人、提供者和患者提供他們正在尋找的所有好處。我們也在努力確保沒有理由在長期內放棄 AMJEVITA。

So we hope that interchangeability, the high concentration and the fact that we already have a citrate-free product on the market, along with the services we provide, along with the fact that this is an Amgen team of people who understand the inflammation indications of this product very well, and they have relationships with the customers that prescribe HUMIRA, we feel really good about the durability of AMJEVITA long term beyond 2024.

因此，我們希望可互換性、高濃度以及我們已經在市場上推出不含檸檬酸鹽的產品這一事實，以及我們提供的服務，以及這是一個了解炎症適應症的安進團隊該產品非常好，並且他們與開 HUMIRA 處方的客戶有關係，我們對 AMJEVITA 2024 年以後的長期耐用性感到非常滿意。

Okay. The next question is from Umer Raffat from Evercore, and he has 2 questions. The first one is for you, Dave, on OX40 and the monthly dosing in Phase III. He said, and I don't see an arm investigating extended intervals quarterly or biannually. I'm just trying to tie the Phase III dosing interval versus the durable efficacy seen through 6 months post last dose. And the second question is for you, Peter, that the tax rate stepped up from 14% to 18% to 19%. Just wanted to get some additional color.

好的。下一個問題來自 Evercore 的 Umer Rafat，他有 2 個問題。第一個是給你的，戴夫，關於 OX40 和第三階段的每月劑量。他說，我沒有看到一個部門每季度或每半年調查一次延長的間隔。我只是想將 III 期給藥間隔與最後一次給藥後 6 個月的持久療效聯繫起來。第二個問題是給你的，彼得，稅率從 14% 提高到 18% 再到 19%。只是想得到一些額外的顏色。

Yes. Regarding the dosing of rocatinlimab. As we've indicated before, we will explore different dosing paradigms here. And as that suite of Phase III trials fully launches, I think it will become clear what we're looking for there based on both the mechanism of action of the molecule as well as patient convenience. Peter?

是的。關於 rocatinlimab 的劑量。正如我們之前指出的，我們將在這裡探索不同的劑量範例。隨著那套 III 期試驗的全面啟動，我認為基於分子的作用機制和患者的便利性，我們在那裡尋找的東西將會變得清晰。彼得？

Umer, good question on tax. Again, it's just a change in what I would say the real estate on the P&L, which is the PRET moves from the cost of sales line down to income tax expense in connection with the change in Puerto Rico for us from a PRET to the actual income tax in Puerto Rico, which began here in 2023. So that's the nature of that change and that's where the 18% to 19% comes in from where we've been here historically.

嗯，關於稅收的好問題。再一次，這只是我所說的損益表上房地產的變化，這是與我們在波多黎各從 PRET 到實際的變化有關的 PRET 從銷售成本線下降到所得稅費用波多黎各的所得稅，於 2023 年在這裡開始。這就是這種變化的本質，這就是 18% 到 19% 來自我們歷史上一直在這裡的地方。

Okay. The next question is from Jay Olson of Oppenheimer. And Jay is asking, can you talk about your plans for geographic diversification? It seems like ex U.S. revenues have become a smaller percentage of Amgen's total revenues over the past few quarters. And we were wondering what underlying dynamics drove that shift in geographical mix, and if there are any future launches or other dynamics that might push the geographical mix back in favor of ex U.S. growth.

好的。下一個問題來自奧本海默的傑伊·奧爾森。傑伊問，你能談談你的地域多元化計劃嗎？在過去的幾個季度裡，美國以外的收入似乎在安進總收入中所佔的比例較小。我們想知道是什麼潛在動力推動了地域組合的轉變，以及是否有任何未來的推出或其他動力可能會推動地域組合回到有利於美國以外的增長。

Yes, we are actually very pleased with the expansion internationally of the Amgen footprint being in over 100 markets. We continue to launch products and secure reimbursement around the world. I talked about LUMAKRAS. And most recently, in China, we've been able to secure national reimbursement drug listing for both Prolia and Repatha. Our Japanese affiliate is growing well.

是的，我們實際上對 Amgen 足跡在 100 多個市場的國際擴張感到非常高興。我們繼續在全球推出產品並確保報銷。我談到了 LUMAKRAS。最近，在中國，我們已經能夠確保 Prolia 和 Repatha 的國家報銷藥物清單。我們的日本子公司發展良好。

In the recent history, I think what you're seeing is a function of just timing of launches coming a bit earlier in the U.S. and also some of our partnering products. I think longer term, what we've got is a very interesting portfolio of products that will continue to make their way around the world.

在最近的歷史中，我認為你所看到的只是美國更早發布的時間以及我們的一些合作產品的功能。我認為從長遠來看，我們所擁有的是一個非常有趣的產品組合，這些產品將繼續在世界範圍內流行。

The announced Horizon acquisition has a very large opportunity internationally. And we see our JPAC region is actually our fastest-growing potential opportunity longer term. So I wouldn't look at short-term movement from quarter-to-quarter. The long-term prevailing trend is that we will grow quickly outside the United States.

已宣布的 Horizon 收購在國際上具有非常大的機會。我們看到我們的 JPAC 地區實際上是我們增長最快的長期潛在機會。因此，我不會關注季度間的短期變動。長期的主流趨勢是我們將在美國以外的地區快速發展。

Okay. The next question is for you, Murdo, from Michael Schmidt of Guggenheim Partners. And he's asking, how confident are you in achieving low double-digit Otezla growth in 2023 and beyond, given the current pattern of essentially flat sales since 2020 of $2.2 billion?

好的。 Murdo，下一個問題來自 Guggenheim Partners 的 Michael Schmidt。他問，鑑於目前自 2020 年以來 22 億美元的銷售額基本持平的模式，您對在 2023 年及以後實現低兩位數的 Otezla 增長有多大信心？

Yes, I think we remain quite confident in our long-term growth of Otezla. We are in a period where there's a lot of new product entrants in the market competing for new patient starts. I think the unique positioning of the product, as I mentioned, allows us to source a very large pool of patients. And our coverage around the world and particularly in the U.S. from an insurance reimbursement perspective allows us to penetrate that market. So we feel very good about the continued prospects to grow Otezla.

是的，我認為我們對 Otezla 的長期增長仍然充滿信心。我們正處於市場上有很多新產品進入者競爭新患者開始的時期。正如我所提到的，我認為該產品的獨特定位使我們能夠找到大量的患者。從保險報銷的角度來看，我們在全球範圍內的覆蓋範圍，尤其是在美國，使我們能夠滲透到該市場。因此，我們對 Otezla 的持續發展前景感到非常樂觀。

Okay. The next question is from Robyn Karnauskas from Truist Securities. So she's asking, big picture, your guidance implies potentially flat growth. Given biosimilar pressures and pricing pressures, do you think 2023 is a trough year? And regarding the guidance range, can you give pushes and pulls on the biosimilar range?

好的。下一個問題來自 Truist Securities 的 Robyn Karnauskas。所以她問，從大局來看，你的指導意味著可能會持平增長。鑑於生物仿製藥壓力和定價壓力，您認為 2023 年是低谷年嗎？關於指導範圍，您能否推動和拉動生物仿製藥範圍？

So Robyn, maybe I'll start on the last piece, and then Pete, you can reiterate what we said about '23. But as I said in my remarks, Robyn, we have 6 further similar launches planned between now and the end of the decade in the United States and other countries around the world. And it is the launch of those molecules through time, which will enable us to continue to grow that franchise.

所以 Robyn，也許我會從最後一篇開始，然後是 Pete，你可以重申我們對 23 年所說的話。但正如我在發言中所說，羅賓，從現在到本十年末，我們還計劃在美國和世界其他國家進行 6 次類似的發射。隨著時間的推移，這些分子的推出將使我們能夠繼續擴大特許經營權。

So I would reiterate what I said earlier in my prepared comments. I think you've heard Murdo address as well the attractive opportunities that we think we'll have here, in particular, with AMJEVITA, though it's -- we're in the first day of launch. And with respect to '23, Pete, I don't know whether you want to say anything in addition to what you already have about the outlook for the year.

因此，我要重申我之前在準備好的評論中所說的話。我想你已經聽到 Murdo 談到了我們認為我們將在這裡擁有的有吸引力的機會，特別是 AMJEVITA，儘管它 - 我們正處於發布的第一天。關於 23 年，Pete，我不知道除了你已經對今年的前景有什麼看法之外，你是否還想說點什麼。

Thanks. I think we covered it earlier. I'd just note a couple of items that happened in 2022 that we didn't expect benefit from in '23, just to reiterate those. We don't expect any and assume any COVID-19 antibody revenues in '23. We're assuming a lower amount of Nplate sales in '23, Robyn, compared to '22. Recall, '22 had the significant purchase by the U.S. government in the second half of the year. We had several favorable changes to estimated sales deductions that occurred in '22, and we sold the generics business in Turkey, which closed late in '22. So a couple of puts and takes around those.

謝謝。我想我們之前已經介紹過了。我只是注意到 2022 年發生的一些項目，我們沒有預料到 23 年會從中受益，只是為了重申這些。我們不期望並假設 23 年有任何 COVID-19 抗體收入。與 22 年相比，Robyn，我們假設 23 年 Nplate 的銷售額較低。回想一下，22 年下半年美國政府進行了大量採購。我們對 22 年發生的估計銷售扣除額進行了一些有利的更改，我們出售了土耳其的仿製藥業務，該業務於 22 年末關閉。所以一些 puts 和 takes around 那些。

And so we look forward to a year in 2023 with strong growth in our priority products, TEZSPIRE, EVENITY, Repatha, Prolia, TAVNEOS. And also -- and that's in light of -- consistent with the industry trends we talked about in our recent history with mid-single-digit price declines in our portfolio, but good volume growth. I think maybe to go back to the question Jay asked, too, we expect strong volume growth outside the United States in 2023. So we're looking forward to taking on '23 with a lot of aggressiveness.

因此，我們期待 2023 年我們的優先產品 TEZSPIRE、EVENITY、Repatha、Prolia 和 TAVNEOS 實現強勁增長。而且——這是鑑於——與我們在最近的歷史中談到的行業趨勢一致，我們的投資組合中的個位數價格下降，但銷量增長良好。我想也許也可以回到 Jay 提出的問題，我們預計 2023 年美國以外的銷量將強勁增長。因此，我們期待著積極進取地迎接 23 年。

Okay. The next question is from Matt Phipps of William Blair. And Matt's saying the oncology biosimilar 2023 guidance suggests a year-over-year decline of 38% versus a 30% year-over-year decline from '21 to '22. Is the rate of erosion in the oncology biosimilars expected to continue to get larger beyond 2023 or will this eventually hit something of a floor?

好的。下一個問題來自威廉·布萊爾的馬特·菲普斯。 Matt 表示，腫瘤學生物仿製藥 2023 年指南表明，從 21 年到 22 年，同比下降 38%，而同比下降 30%。預計到 2023 年以後，腫瘤生物仿製藥的侵蝕率是否會繼續上升，或者這最終會觸底嗎？

I wouldn't say we expect it to get larger, but we will continue to see a decline in that business, which is a function of the average selling price decline that we've seen thus far.

我不會說我們預計它會變得更大，但我們將繼續看到該業務的下滑，這是我們迄今為止看到的平均售價下降的結果。

Yaron Werber calling. He said I'm confused by the tax rate going up to 18% to 19% while COGS are 16% to 17%. Hence, I don't see any offsets in the COGS line. What am I missing?

Yaron Werber 來電。他說我對稅率上升到 18% 到 19% 而 COGS 是 16% 到 17% 感到困惑。因此，我在 COGS 行中看不到任何偏移量。我錯過了什麼？

I think the answer to that is that our volume growth. The volume growth is quite large, and that's really the offset, Yaron. That's a good question. And so we see that happening. We also -- in terms of the move of the PRET down there, recall, too, in cost of sales this year, we've got $125 million coming in off of the release out of inventory into cost of sales without any corresponding tax provision.

我認為答案是我們的銷量增長。數量增長相當大，這確實是抵消，Yaron。這是個好問題。所以我們看到了這種情況。我們還——就 PRET 的移動而言，還記得今年的銷售成本，我們有 1.25 億美元從庫存釋放到銷售成本中，沒有任何相應的稅收規定.

And so the percent of sales versus the percent of pretax, too, you've got to be thinking about that in terms of the income tax provision itself. So that's the puts and the takes on that. But when you strip it all back, it's really that move of the PRET down into the income tax expense that increases that effective rate to 18% to 19%.

因此，銷售額百分比與稅前百分比的對比，你也必鬚根據所得稅規定本身來考慮。這就是看跌期權和看跌期權。但是當你把它全部剝離時，實際上是將 PRET 轉移到所得稅費用中，將有效稅率提高到 18% 到 19%。

Okay. The next question is from Trung Huynh from Credit Suisse. And Trung said thanks for the comments on Otezla and ENBREL. So can you add a bit more color into the dynamics in immunology? Are there any changes in the channel and mix of patients? Has there been any formulary disruptions?

好的。下一個問題來自瑞士信貸的 Trung Huynh。 Trung 表示感謝對 Otezla 和 ENBREL 的評論。那麼你能為免疫學的動態添加更多色彩嗎？患者的渠道和結構是否有變化？是否有任何處方中斷？

Overall, our immunology business looks very good. I think we're very pleased with the TEZSPIRE launch. We continue to see broad phenotypes of patients, regardless of biomarker status being treated. We are seeing de novo patients who haven't seen a biologic before in their treatment of their uncontrolled asthma. And we're also seeing patients being switched from other products within the class. And so we expect that area of autoimmune disease growing in terms of the biologic penetration of severe uncontrolled asthma, and we're well positioned to compete for that expanded treatment pattern.

總的來說，我們的免疫學業務看起來非常好。我認為我們對 TEZSPIRE 的發布感到非常滿意。我們繼續看到患者的廣泛表型，無論接受治療的生物標誌物狀態如何。我們看到新患者在治療未控制的哮喘時從未見過生物製劑。而且我們還看到患者正在從同類產品中的其他產品轉換過來。因此，我們預計自身免疫性疾病領域會隨著嚴重不受控制的哮喘的生物滲透而增長，我們有能力競爭這種擴大的治療模式。

ENBREL continues to serve many patients. And the trends there are fairly predictable and fairly consistent. Otezla, as we've mentioned, is seeing some pressure from new free drug programs, both for our topicals as well as new entrant oral, SOTYKTU. And then we also have just picked up TAVNEOS, which we're really excited about, a product that treats a severe autoimmune disease, ANCA-associated vasculitis. Very young product, very early in its life cycle, and I think a lot of growth there to be had.

ENBREL 繼續為許多患者服務。那裡的趨勢是相當可預測和相當一致的。正如我們所提到的，Otezla 看到了來自新的免費藥物計劃的一些壓力，包括我們的外用藥物和新進入的口服藥物 SOTYKTU。然後我們也剛剛獲得了 TAVNEOS，我們對此感到非常興奮，這是一種治療嚴重自身免疫性疾病 ANCA 相關血管炎的產品。非常年輕的產品，處於生命週期的早期，我認為會有很大的增長空間。

And then, of course, last but certainly not least, on the branded side, the announced acquisition of Horizon. So I think the inflammation area, along with our own innovative pipeline and the pipeline of Horizon is a very good growth opportunity for us long term. And last but not least, here we are on the first day of launch of a novel biosimilar to the largest product in the U.S., and that's HUMIRA. So I think we've got a lot of opportunities for growth ahead.

然後，當然，最後但同樣重要的是，在品牌方面，宣布收購 Horizon。所以我認為炎症領域，連同我們自己的創新管線和 Horizon 管線對我們來說是一個非常好的長期增長機會。最後但並非最不重要的一點是，我們迎來了美國最大產品 HUMIRA 的新型生物仿製藥上市的第一天。所以我認為我們有很多未來的增長機會。

I think we're down to our last question, Arvind, if you want to read that?

我想我們已經到了最後一個問題，Arvind，你想看嗎？

Yes. Let me read the last question, Bob, and after that, you might have some concluding comments. So the last question is from Brian Skorney of Baird. And Brian wants to know, do you expect this to be more of a longer-term tax rate, assuming no major changes to corporate tax rates in the U.S.?

是的。讓我讀一下最後一個問題，鮑勃，然後你可能會有一些結論性意見。最後一個問題來自 Baird 的 Brian Skorney。 Brian 想知道，如果美國的公司稅率沒有發生重大變化，你是否認為這是一個更長期的稅率？

May I, Arvind? Yes, Brian, I think, as you know, we don't give long-term guidance on tax rates. And so we won't go beyond this year. So 18% to 19% and go back to your own, just to make sure we understand the change in the PRET. The PRET is a percentage of its cost of sales as opposed to the income tax rate, which is pretax income. So that's a little bit of the difference, too, that Yaron asked about. So 18% to 19% this year is where we're at, and that's where we'll -- that's what we'll give you for now.

我可以嗎，阿文德？是的，布賴恩，我認為，如你所知，我們不會就稅率給出長期指導。所以我們不會超過今年。所以 18% 到 19% 回到你自己的，只是為了確保我們理解 PRET 中的變化。 PRET 是其銷售成本相對於所得稅率（即稅前收入）的百分比。所以這也是 Yaron 詢問的一點不同之處。所以今年 18% 到 19% 是我們現在的位置，這就是我們將要達到的位置——這就是我們現在要給你的。

All right. Well, thank you very much, again, for your patience. Apologies that we had a little bit of difficulty with our vendor's connection earlier on the call. So if you have any further questions, shoot them into Arvind. We'll be around here this afternoon, Peter Murdo, Dave and myself, to answer any further questions you might have. And we appreciate your joining the call and look forward to talking to you during the course of 2023. Thank you.

好的。好吧，再次非常感謝您的耐心等待。很抱歉，我們在早些時候的電話會議上遇到了供應商的連接問題。因此，如果您有任何其他問題，請將它們發送到 Arvind。 Peter Murdo、Dave 和我本人今天下午會在這裡，回答您可能提出的任何進一步問題。我們感謝您加入電話會議，並期待在 2023 年期間與您交談。謝謝。

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感謝您使用 Webex。請訪問我們的網站 www..com。