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)

我是Jason，今天我將主持安進公司2022年第四季及全年財務業績電話會議。 （操作說明）

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

現在我謹介紹投資人關係副總裁阿文德‧蘇德先生。蘇德先生，您可以開始了。

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。謝謝傑森。大家下午好，歡迎參加我們關於2022年第四季及全年業績的電話會議。儘管面臨一些宏觀挑戰，2022年依然是執行力卓越的一年。我們的董事長兼執行長鮑伯‧布拉德韋先生將作開場致辭，隨後其他高階管理團隊成員也將作發言。

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連結。在討論過程中，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績效。再次提醒您，實際結果可能與預期有重大差異。

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

那麼，接下來我將把電話交給鮑伯。

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，謝謝各位參加我們的電話會議。我們對公司業務的長期成長前景充滿信心，讓我來談談這五點原因。

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，我們擁有多款創新、銷售驅動型產品，這些產品仍有很大的成長空間，我們在2022年就已經見識到這一點。 Repatha、Prolia和EVENITY在第四季度和全年均實現了兩位數的銷售額和銷售成長。我們預計這些產品在2023年及以後將繼續成長，其中Repatha尤其受益於FOURIER開放標籤擴展研究的重要新數據和新的處方指南。

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在第四季和全年銷量均成長了7%，這得益於其適應症的擴展，使我們能夠惠及美國數百萬患有輕度至中度銀屑病的新患者。 LUMAKRAS和TEZSPIRE全年合計銷售額超過4.5億美元，我們正在積極探索這兩款產品的其他適應症。我們尤其欣喜地看到TEZSPIRE被應用於各種類型的重度氣喘患者。 Murdo稍後將詳細介紹我們現有產品的業績。

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，我們在 2022 年將 6 種同類首創分子推進到 III 期或可能獲得註冊的試驗階段，其中包括用於治療 LP(a) 的 Olpasiran、用於治療特應性皮膚炎的 rocatinlimab、用於治療嗜酸性食道炎的 TEZSPIRE，當然還有用於治療癌症的 bemaritk、LINlatamab、Bemarituz。

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.

我們已開始招募病患參與AMG 133的II期臨床試驗。根據早期數據，這種分子憑藉其獨特的作用機制，似乎在治療肥胖症方面具有吸引力。稍後Dave Reese將為我們帶來更多關於我們研發管線的資訊。

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，我們擁有業界領先的生物相似藥業務，這將持續推動我們的成長。 2022年，我們公佈了針對EYLEA、SOLIRIS和STELARA的生物類似藥候選藥物的積極III期臨床試驗數據，這使我們能夠搶佔先機，成為這些藥物首批上市的候選者，我們深知這對於成功至關重要。

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.

我們在美國推出AMJEVITA不到24小時。 AMJEVITA是國際上領先的HUMIRA生物相似藥。我們比下一個競爭者領先5個月，這讓我們在美國市場佔據了有利地位。總而言之，從現在到本十年末，我們計劃在美國和全球其他市場推出另外6款生物相似藥，這將為我們帶來另一個長期成長點。

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，我們曾多次表示，我們會尋求在既定策略重點領域進行許可和收購。而我們也正是這樣做的，憑藉我們在發炎領域數十年的經驗，我們完成了兩項重大交易，這將進一步鞏固我們在該領域的地位。透過收購ChemoCentryx，我們獲得了TAVNEOS——一種用於治療ANCA相關性血管炎的首創療法，我們在這個領域取得了良好的開端。

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.

我們宣布收購Horizo​​​​n Therapeutics將新增多款處於早期研發階段的同類首創生物製劑，包括TEPEZZA、KRYSTEXXA和UPLIZNA，這將助力我們實現2030年及以後的成長。目前，我們正在推進該交易的監管審批流程，並確信該交易不存在任何反競爭問題。此外，我們已收到美國聯邦貿易委員會（FTC）的第二次問詢，我們將積極配合解答相關問題，並保持樂觀，相信我們能夠在今年上半年完成交易。

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，我們始終堅持資本配置原則，投資於業務發展以推動長期成長，同時透過股票回購和不斷提高的股利向股東返還資本。稍後您將聽到Peter對此的更多闡述。我們去年取得的所有成就以及未來將取得的所有成就，都歸功於員工的辛勤工作和奉獻精神。他們對服務患者的使命充滿熱情，清楚地認識到自己的工作如何為公司的成功做出貢獻，並已做好準備迎接機會和挑戰。我衷心感謝他們所有人。

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

我期待稍後回答您的問題，但現在，讓我把電話交給默多。

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，鮑伯。 2022年，我們繼續出色地履行使命，致力於為全球數百萬患有重疾的患者提供（聽不清楚）產品。我們的產品組合持續發展，16個品牌的銷售額均創歷史新高。我們的普通內科和血液腫瘤增長型品牌銷量均實現了強勁增長。隨著TEZSPIRE的上市和對TAVNEOS的收購，我們的發炎治療領域得到了拓展，這兩款藥物均為同類首創，用於治療嚴重疾病。

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Horizo​​​​n Therapeutics將為我們的產品組合新增多種重要藥物。 2022年全年銷售成長9%，其中美國市場成長7%，美國以外市場成長14%，我們持續推動國際成長策略。剔除匯率影響，全年全球產品銷售成長4%，銷售成長被淨售價下降5%所抵銷。計入2%的匯率負面影響，產品銷售額年增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.

本季度，我們的銷量也實現了強勁成長，年成長10%。首先來看我們的普通藥品業務，包括Prolia、EVENITY、Repatha和Aimovig，這四款產品的總收入在第四季度同比增長21%，全年同比增長18%，分別得益於銷量增長19%和21%。

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.

在骨骼健康領域，Prolia第四季銷售額年增14%，主要得益於銷售量成長11%。 EVENITY是Prolia在骨骼產品組合中的補充，該季度銷售額創下2.25億美元的紀錄，這主要得益於各市場銷量的強勁增長。 Repatha第四季銷售額年增22%，銷售量成長31%，但部分被淨售價下降抵銷。

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，第四季度銷量增長了32%，這得益於心臟病專家對瑞百安（Repatha）的廣泛採用以及初級保健醫生對該藥物的接受度不斷提高。由於我們提高了回扣以支持更廣泛的聯邦醫療保險D部分（Medicare Part D）和商業保險患者獲得該藥物，因此美國市場的淨售價有所下降。展望2023年，我們預期美國市場的價格年減幅度將小於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，Repatha第四季銷售額年增36%，主要得益於銷量成長31%。自上市以來，Repatha已在全球治療了超過150萬名患者。 Repatha在心臟病學領域擁有良好的處方記錄，並在基層醫療機構中得到更廣泛的應用，這使我們能夠更好地將Repatha推廣至全球更多患者。憑藉FOURIER研究的長期追蹤數據，以及不斷更新和更積極的治療指南，我們有充分的理由相信，儘早使用Repatha盡可能降低低密度脂蛋白膽固醇（LDL-C）水平，將有助於降低全球患者的心血管風險。

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.

轉向我們的炎症治療產品組合。 Otezla 的季度銷售額較去年同期下降 2%，全年銷售額較去年同期成長 2%。兩個時期銷量均成長 7%。銷售下降被淨售價降低所抵消，淨售價降低的原因是，我們改進了共同支付和患者援助計劃，以支持新患者開始治療，並提供了額外的折扣以提高醫保覆蓋範圍。

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，由於新推出的局部用藥和全身用藥競爭產品，導致三個藥物項目的新患者需求增加，我們的美國Otezla業務受到影響。我們預計這種影響將持續到2023年第一季。此外，由於保險覆核、病患自付額和免賠額等因素的影響，我們預期第一季的銷售額將低於後續季度，這符合典型的市場規律。綜合這些因素，Otezla第一季的銷售額可能與2022年第一季持平或更低。

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，鑑於 Otezla 已確立的安全性、強大的醫保覆蓋範圍（事先授權要求有限）以及便捷的給藥方式，我們仍然看好其強勁的成長潛力。 Otezla 仍然是目前唯一獲準的適應症廣泛的口服系統性治療藥物，有望幫助美國 400 萬輕度至中度乾癬患者，其中 150 萬名患者的病情無法透過局部用藥得到最佳控制，而 Otezla 等一線系統性治療藥物能夠為他們帶來益處。

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.

受銷售量和淨售價下降的影響，恩利（ENBREL）第四季銷售額年減1%，部分被年末庫存水準上升所抵銷。由於其長期療效和安全性記錄良好，恩利仍然是患者的重要藥物。

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 上市後持續強勁成長，第四季銷售額達 7,900 萬美元，全年銷售額達 1.7 億美元。過敏科醫生和肺科醫生已將 TEZSPIRE 開給眾多患有嚴重未控制氣喘的患者。我們也看到，TEZSPIRE 開始用於治療既往未接受過生物製劑治療和未接受過生物製劑治療的患者。

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.

醫師們認可TEZSPIRE獨特的差異化特性，認為其具有廣泛的治療潛力，能夠治療全球250萬重度難治性氣喘患者，且不受任何表型和生物標記限制。我們目前正積極準備，預計預填充注射筆將於第一季獲得美國批准，屆時患者將能夠在家中便捷地使用TEZSPIRE。

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.

第四季TAVNEOS的銷售額為2100萬美元。我們對ChemoCentryx的整合進展順利，這印證了我們的信念：安進在發炎和腎臟病領域的深厚經驗以及強大的市場地位，將使我們能夠為更多ANCA相關性血管炎患者帶來TAVNEOS。

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.

我們很高興地宣布收購Horizo​​​​n Therapeutics。合併後的產品組合將包括TEPEZZA、KRYSTEXXA和UPLIZNA，這些藥物將用於治療嚴重的發炎性疾病，並改善眾多患者的生活。安進的商業實力和遍布全球約100個市場的業務佈局，將使我們的團隊能夠提供重要的治療方案，為全球更多患者帶來實際的改變。

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，這是美國第一個HUMIRA生物相似藥。 HUMIRA是一種用於治療嚴重發炎性疾病的藥物，目前已有超過100萬名患者使用。憑藉我們在生物製劑研發和生產方面的豐富經驗，以及在發炎領域數十年的專業積累，安進擁有得天獨厚的優勢，能夠為患者提供這款生物相似藥。 AMJEVITA是美國首個進入健保報銷範圍的重要生物相似藥，我們預計隨著市場的發展，未來幾個月內其市場份額將逐步擴大。

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.

接下來談談我們的血液腫瘤業務，其中包括LUMAKRAS、KYPROLIS、XGEVA、Vectibix、Nplate和BLINCYTO。這六款創新產品年增14%，季銷量成長17%。全年銷售額成長13%，主要得益於銷量成長。 KYPROLIS第四季銷售額成長14%。 Nplate第四季銷售額包含來自美國政府的一筆一次性訂單，金額為2.07億美元。鑑於我們血液腫瘤產品組合在2022年的強勁表現，以及BLINCYTO和Vectibix近期公佈的正面數據，我對該產品組合未來的成長潛力充滿信心。

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第四季銷售額為7,100萬美元，全年銷售額為2.85億美元。儘管銷量成長12%，但環比銷售額下降5%，而淨售價下降抵消了這一增長。淨售價下降的主要原因是法國一項報銷審批決定導致1,200萬美元的不利價格調整，以及預估銷售扣減額的不利變化。

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.

除美國外，LUMAKRAS 已在超過 45 個國家獲得批准。我們已在 30 個市場推出 LUMAKRAS，並正在迅速爭取在其餘國家/地區獲得醫療保險報銷。正如我們之前提到的，LUMAKRAS 的市場主要集中在美國 7,000 名患者和美國以外 20,000 名患者，用於二線治療。從長遠來看，我們預計 LUMAKRAS 的成長將來自於其在早期治療領域的應用以及對更多腫瘤類型的適應症。

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.

受價格下跌的影響，我們腫瘤生物相似藥第四季銷售額年減40%，全年年減30%。儘管MVASI和KANJINTI的生物相似藥均佔據市場領先地位，但我們預計，在競爭加劇的推動下，淨售價將持續惡化，銷售量也將加速下滑。最新公佈的美國平均售價顯示，MVASI年減38%，KANJINTI年減51%。展望未來，我們預期生物相似藥業務的長期成長將主要得益於新分子的加入和更多產品的上市。

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.

新年伊始，我深受安進全球數千名員工的辛勤付出所鼓舞，他們每天早起，竭誠為病患服務。我們不斷拓展的國際業務和多元化的產品組合，加上對ChemoCentryx的整合以及已宣布的對Horizo​​​​n的收購，使我們能夠更好地服務全球更多患者。

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

接下來，我將把麥克風交給戴夫。

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。在研發方面，去年我們有效率執行，準時交付成果，持續推動創新產品線。在一般醫學領域，我們加強了心血管產品線和新興的肥胖症產品組合，這兩個領域都存在著巨大的未滿足醫療需求，影響著全球數百萬名患者。

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，瑞百安（Repatha）是這些努力的基石。去年11月，我們在美國心臟協會（AHA）年會上發表了FOURIER開放標籤擴展研究的數據。這些數據得到了美國心臟學會專家共識決策路徑的認可，顯示似乎不存在任何LDL膽固醇水平低於該值時獲益停止的情況。此外，LDL膽固醇的建議值也進行了更新，將高風險患者的LDL目標值從70毫克/分升高到55毫克/分升。對於許多未接受PCSK9抑制劑治療的患者而言，這個目標值是無法達到的。

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.

我們非常關注的另一種分子是 Olpasiran。在 AHA 會議上，我們公佈了 II 期臨床試驗數據，結果顯示，對於基線 Lp(a) 水平約為 260 納摩爾/公升的已確診動脈粥樣硬化性心血管疾病患者，每 12 週給予 75 毫克或更高劑量的 Olpasiran 可使 Lp(a) 濃度降低 95% 至 100%。研究顯示 Olpasiran 安全性良好，耐受性也佳。

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.

這些數據令人鼓舞，尤其是給藥頻率、安全性和耐受性以及Lp(a)降低程度。我們已啟動一項III期療效研究，納入6,000名患有動脈粥狀硬化性心血管疾病且Lp(a)水準顯著升高（至少200奈摩爾/公升）的受試者。

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.

現在我們來談談肥胖症。去年12月，我們公佈了一項I期研究的數據，結果顯示AMG 133安全、耐受性良好，在連續3個月每月皮下注射後，第85天體重平均減輕了14.5%。在最後一次AMG 133給藥後，體重減輕的現象可持續長達150天。鑑於這些良好的特性，我們目前正在進行一項II期研究，招募570名受試者，以探討AMG 133在有或沒有糖尿病及相關合併症的肥胖症患者中的應用。研究也將考察不同的劑量水平和給藥方案。

(technical difficulty)

（技術難題）

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.

各位請注意。很抱歉故障。本次通話將轉至 Webex 平台。 Webex 的撥入號碼是 1 (844) 992-4726。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.

（技術難題）較去年同期下降兩個百分點，至16.3%。全年來看，銷售成本佔產品銷售額的百分比下降0.5個百分點，至15.9%。季度和全年業績的改善主要歸功於新冠病毒抗體出貨量減少和生產成本降低，但部分被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%.

第四季非GAAP研發支出較去年同期下降2%，主要原因是2021年業務拓展活動增加，包括我們與Generate Biomedicines和Arrakis Therapeutics合作相關的預付款，以及上市產品支援減少。早期和後期專案關鍵資產支援增加部分抵消了上述影響。然而，剔除2021年業務拓展活動的影響後，2022年第四季研發投資年增7%。全年非GAAP研發支出較去年同期下降8%，原因與第四季相同。然而，剔除業務拓展活動的影響後，2022年全年研發投資成長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.

第四季非GAAP銷售、管理及行政費用年增2%，主要得益於市場推廣產品支援的增加，包括對重點產品TEZSPIRE、EVENITY和Repatha的投資。全年來看，銷售、管理及行政費用與去年持平，原因是所有重點品牌的投資增加被生產效率提升、持續改善以及成熟品牌的資源重新分配所抵銷。第四季非GAAP其他收入和支出約為4.7億美元，年增2.5億美元，主要原因是先前已確認的2021年對百濟神州投資的收益。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.

現在我們來展望一下2023年的業務前景。我們的展望僅基於安進公司本身，未對已宣布的Horizo​​​​n收購進行任何調整。需要注意的是，目前公開的共識預期是基於安進公司自身業績的預期，以及部分分析師已將Horizo​​​​n納入其預期之後得出的綜合數據。因此，我們預計2023年營收為260億美元至272億美元，非GAAP每股收益為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績效指引相關的幾個關鍵點。關於總收入，我們預計年比數據將不包含約7億美元的收入，這些收入與2022年的幾項項目有關，而我們預計這些項目在2023年不會產生收益。我們假設2023年不會產生新冠病毒抗體相關的收入。我們也假設2023年Nplate的銷售額將低於2022年。需要注意的是，2022年下半年美國政府對Nplate進行了大筆收購。

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 年銷售額預估扣除額也出現了一些有利變化，而我們在土耳其的仿製藥業務已於 2022 年底完成出售。產品銷售方面，我們預期整體產品組合的銷售將有所成長，這主要得益於我們的重點產品 TEZSPIRE、EVENITY、Repatha、Prolia 和 TAVNEOS 的強勁成長。與行業趨勢和我們近期的業績一致，我們預計 2023 年產品組合的價格將出現中等個位數的下降。

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.

接下來談談Neulasta和我們的腫瘤生物相似藥。我們預計近期的趨勢將持續到2023年。這可能導致Neulasta全年銷售額低於7億美元。此外，我們預期腫瘤生物相似藥KANJINTI和MVASI的合併銷售額將低於7.5億美元。最後，由於我們與DaVita的合約即將到期，我們預計EPOGEN的銷售額將低於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.

全年其他收入預計在12億至15億美元之間。需要注意的是，我們在2022年與禮來公司合作研發新冠抗體時確認了約3億美元的收入，預計2023年不會再有類似收入。因此，我們將繼續以以往的成本控制原則管理營運費用。即便2023年銷售成長、淨售價下降以及成本面臨通膨壓力，我們仍預期全年非GAAP營運費用與2022年持平，因為我們將繼續致力於提升整個企業的生產力和成本效益。

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.

我們預期非GAAP銷售成本佔產品銷售額的16%至17%。回顧我們在第三季財報討論中提到的，波多黎各於2022年6月頒布的稅法變更以所得稅取代了波多黎各消費稅（PRET）。這項變更將從2023年開始增加我們的所得稅費用，同時使我們的銷售成本大致減少相同的金額。但需要注意的是，2023年將產生約1.25億美元的負面影響，這部分影響與目前已資本化計入存貨的PRET有關，該部分稅款將在2023年上半年計入銷售成本，其中大部分費用將在第一季度確認，且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年非GAAP研發費用將比2022年成長3%至4%，這主要得益於我們推進了Reese博士先前提及的多個計畫。這符合我們優先投資最佳創新項目的資本配置原則，而我們嚴格的營運費用控制也為我們提供了實現這一目標所需的資金。至於非GAAP銷售、管理及行政費用，我們預計2023年該支出佔產品銷售額的比例將略有下降，主要得益於生產效率的提高。

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.

上述因素共同導致我們預期全年非GAAP營業利潤率（佔產品銷售額的百分比）約為50%。我們預計非GAAP其他收入和支出約為14億美元。預計同比改善主要得益於我們2023年對百濟神州投資會計處理的變更。自2023年1月起，我們將不再依照權益法在非GAAP損益表中計入我們在百濟神州的份額，而是將投資按市值計價，並將影響力僅計入GAAP損益表。

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%。該稅率反映了新的波多黎各所得稅，正如我之前解釋的，該稅種已於2023年取代了先前的PRET稅。我們預計2023年股票回購額不會超過5億美元，並將持續大幅提高股利。我們預計2023年資本支出約為9.25億美元，符合我們優先投資於業務發展的資本配置策略，包括投資我們在俄亥俄州和北卡羅來納州新建的環保設施。這些設施建成後，我們預計資本支出將恢復到歷史水準。

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.

我還想就2023年第一季做一些具體說明。令人欣慰的是，我們業務在今年第一個月的表現符合預期。然而，根據我們以往的營收模式，我們預計今年第一季的營收將是全年最低的季度，略低於2022年第一季。從產品組合層面來看，我們預計產品銷售額將與2022年第一季持平，而其他收入將同比下降，原因如上所述，其中包括2022年第一季約2.25億美元的新冠抗體銷售收入。

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.

我們預計2023年第一季將面臨約8,000萬美元的外匯不利影響，與2022年第一季相比。所有這些因素加起來，將造成超過4億美元的不利影響，與2022年第一季相比。因此，這些收入模式以及費用發生的時間安排，預計將導致我們2023年第一季的非GAAP營業利潤率（佔產品銷售額的百分比）低於50%，儘管我們仍然預計2023年全年營業利潤率（佔產品銷售額的百分比）將保持在50%左右。請注意，以上所有數據均指安進獨立營運的情況。我們將繼續秉承我們卓越的執行力傳統。

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，儘管面臨宏觀經濟逆風，我們在2022年依然取得了強勁的財務業績，確保我們能夠按計劃實現2030年及以後的長期目標。我們對安進的長期成長充滿信心，並期待在2023年上半年完成先前宣布的對Horizo​​​​n的收購，這將進一步增強我們的成長前景。交易完成後，我們將視情況適時發布更新後的業績指引。

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。感謝安進全球兩萬五千多名同事，感謝他們致力於服務患者，並在2022年付出了不懈努力。

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

現在我將把問答環節交還給鮑伯。

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。謝謝Peter和Dave克服技術困難堅持。再次向所有撥入電話會議並因此受到干擾的朋友們致歉。

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.

很多朋友已經透過電子郵件向Arvind提出了問題。我建議大家現在就直接把問題寄給Arvind，他會閱讀這些問題。我們會盡量在這次會議上解答。另外，請大家放心，如果這次電話會議沒能解答到所有問題，我們會調整行程安排，會議結束後，Arvind和他的團隊會繼續解答大家的問題。

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

那麼，接下來就請 Arvind 來解答你們已經提交的問題。

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，謝謝鮑伯。也向大家致歉，我們遇到了一些技術問題。正如鮑伯所說，請直接寄電子郵件給我提問。

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?

我們收到的第一個問題來自Cowen公司的Yaron Werber，他提出了兩個問題。第一個問題是，安進是否會將百濟神州的會計處理方法從權益法改為公允價值法。鑑於您目前持有百濟神州不到19.9%的股權，安進是否會停止合併百濟神州的損益？第二個問題是，一旦您在2023年上半年獲得AMJEVITA的III期可互換數據，您能否說明一下何時提交AMJEVITA的高集中度上市申請？

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，你先來回答會計方面的問題吧？

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，問題很簡單，答案也很簡單。謝謝Yaron的提問。關於百濟神州的權益法會計處理，如我剛才所說，我們會依照GAAP準則編制損益表，但不會將其計入非GAAP損益表。所以答案是，今後我們不會將百濟神州的任何收益或虧損計入非GAAP損益表。

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。至於AMJEVITA，我們為什麼不做個兩集節目呢？戴夫·里斯和默多，你們或許可以補充一些想法。

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。關於申報時間表，一旦我們掌握了數據，在與相關監管機構進行必要的溝通後，我們將給出預計的申報時間和可能的審批時間。我認為，正如鮑勃·布拉德韋所指出的，這一點很重要，我想請默多就此發表一下看法。

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。正如您所想，鑑於我們正在進行產品上市，今天我們收到了一些關於這方面的諮詢。目前，上市進展順利。我們的產品正在陸續進入管道，並且已經收到來自支付方、處方醫生和患者的關於AMJEVITA的諮詢。

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.

需要記住的一點是，我們目前市場上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，這意味著我們仍然可以透過使用不含檸檬酸鹽的配方來最大限度地減少注射部位的疼痛，從而為患者帶來更好的體驗。

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，患者體驗一直很積極，我們預期藥物濃度不高不會成為市場障礙。這些藥物的注射量非常低，透過自動注射筆注射。而且，我們發現患者能夠非常可靠地自行注射。

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.

當然，我們也為患者提供護理師支援。另外，雖然沒有被問到，但我認為同樣重要的是，在產品上市之際，我們也為處方醫生和患者提供經濟援助、支持和報銷支持。因此，我們為首個在美國上市的生物相似藥——阿達木單抗（adalimumab）——提供了您期望品牌藥上市時所享有的全方位服務和支持，這就是AMJEVITA。

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

好的。謝謝默多和戴夫。我們進入下一個問題，阿文德。

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.

下一個問題來自美國銀行美林證券的傑夫‧米查姆。他的問題是，我知道你們有AMJEVITA，但你們是否預期所有HUMIRA生物相似藥和STELARA會在2023年下半年或2024年上半年對Otezla和ENBREL產生間接影響？他主要關注的是銷量和價格方面的影響。

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

好的。默多，你想分享一下你的看法嗎？

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，我很難評論競爭對手在7月之後其他阿達木單抗生物相似藥上市後可能會採取的行動。但進入2023年，我們看到醫保報銷談判進展順利，我們成功為恩利（ENBREL）和歐特茲拉（Otezla）爭取到了非常廣泛的醫保覆蓋。我們預計這種健保覆蓋將持續到2023年底。和往年一樣，為了獲得如此廣泛的健保覆蓋，我們在淨價方面做出了一些小的讓步，但這與往年相比並無異常之處。

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

謝謝。我們來看下一個問題。

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，他有兩個問題。第一個問題是關於Otezla的。 Chris說：“我知道目前市場上對這個藥物的買賣雙方都有很多看法，我也知道你們強調了輕度至中度銀屑病患者接受治療的利好因素。但Otezla的特殊之處在於它的停藥率相當高。”

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.

既然您可能不會離開，那就談談為什麼我們不應該更擔心SOTYKTU，以及同樣重要的，即將推出的下一代TYK2分子。尤其值得注意的是，即使庫存增加了9%，美國和世界其他地區的季度環比仍然下降，您能否就如何應對即將到來的競爭提供一些見解，這將非常有幫助。然後，他還有一個關於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。首先說說Otezla，我想先強調一點：我們是唯一一款適用於各種嚴重程度銀屑病患者的全身性藥物，這使我們成為局部治療後理想的首選全身性治療方案。這就是我們的品牌定位。這個市場規模非常龐大。全球有400萬輕度至中度乾癬患者。其中約有150萬名患者若局部治療效果不佳，可能需要改用像Otezla這樣的全身性藥物。

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 的一線治療途徑非常廣泛，也就是說，它無需患者接受其他系統性治療。這也意味著醫生可以將其作為首選藥物。而皮膚科醫生工作繁忙，他們需要的是簡單易行的治療方案，無需繁瑣的術前準備工作，並且能夠讓患者快速開始治療。在銀屑病治療市場，只有 Otezla 能夠滿足這些需求。

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.

我認為我們目前看到的現像是去年底啟動並延續到本季的多項免費藥品計畫所帶來的影響。當醫生們擁有免費藥品計劃（有時也稱為過渡計劃，通常在產品上市初期，當尚未有機會透過藥品福利管理機構獲得藥品供應時使用）時，醫生有時會利用這些計劃來嘗試新上市的療法。

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，當這些新型療法與藥品福利管理機構 (PBM) 和支付方進行談判時，往往會因為其准入機制的特殊性而使嘗試這些新型療法變得更加困難。我認為，Otezla 在第一線全身性、局部用藥後、生物製劑治療前患者群體中持續的優勢，正是為我們提供了長期成長機會的關鍵所在。我們對該品牌的長期成長充滿信心。

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.

我們在全球多個市場擁有非常強大的商業影響力，而且從我們的皮膚科醫生處方群體那裡得到的回饋也讓我們倍感鼓舞。我想說的是，我們正在密切關注這些免費贈品項目的短期影響，並確保我們在市場上保持競爭力。

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。克里斯的第二個問題和高盛的薩爾文·里希特提出的問題一樣。她說，關於AMJEVITA，您能否詳細說明雙重定價方案將如何運作並推動銷售成長？我們該如何看待淨價？隨著更多生物相似藥的上市，您對年中市場有何預期？

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.

嗯，或許我可以先回答第二個問題。我們不會對具體產品的定價發表評論，所以我真的無法回答淨價問題。我認為可以肯定的是，隨著更多競爭者進入市場，淨價通常會下降，我們在其他生物相似藥業務中也看到了這一點，我們預計這種情況也會發生在我們這裡。

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.

關於我們在此次發表會上採用的兩種定價策略，這主要是為了因應美國市場的複雜性。藥品福利管理機構的商業模式要求他們與生產商協商回扣，因此他們傾向於採用較高的定價，然後透過協商回扣來降低成本，最後將這些回扣轉給上游的雇主客戶。

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一些利害關係人和客戶更傾向於淨價模式，他們並不關心標價和淨價或毛價和淨價之間的差異。因此，我們為他們提供淨價較低的產品。再次提醒一下，我們的標價較高，比修美樂（HUMIRA）低5%；我們的標價較低，比修美樂（HUMIRA）低55%。

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.

我們還計劃透過提供共付額援助以及幫助患者透過保險公司獲得報銷，確保AMJEVITA成為患者能夠負擔得起的藥物。此外，我們很高興地宣布，在上市首日，我們的產品就已與三大全國性藥品福利管理機構（PBM）達成合作，實現了廣泛的覆蓋範圍，與HUMIRA享有同等的療效。

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?

我注意到現在已經過了半小時，但我們會繼續回答問題，直到所有問題都得到解答，並且我們會錄製下來，以文字稿的形式提供給那些有時間衝突無法繼續參加的觀眾。那麼，Arvind，你來回答下一個問題吧？

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。這是一個關於肥胖症治療產品線的問題。我們今年應該期待什麼更新？我們會看到I期研究剩餘3個隊列的資料嗎？另外，關於AMG 786，我們什麼時候能看到關於該藥物和項目的更新和更多資訊揭露？

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。關於肥胖症治療產品線，AMG 133，以及您提到的另外兩個隊列，我不確定今年能否獲得相關數據。如果情況有變，我當然會及時告知。 AMG 786 是一種作用機制不同的小分子藥物，它是一種 GLP-1 或 GIPR 受體激動劑或拮抗劑。因此，它正在進行劑量遞增試驗。我會告知大家何時可以獲得該項目的數據。當然，一旦數據可用，我們也會討論其靶點。

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

好的。謝謝你，大衛。阿文德，我們來看下一個問題。

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?

下一個問題來自BMO資本市場的Evan Seigerman。 Evan想知道，隨著LUMAKRAS銷售放緩，您能否詳細說明您是如何調整商業策略，以更好地發揮這些資產的商業潛力？

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售成長是否放緩。我認為我們看到的情況是，正如我之前提到的，可能在音頻中沒有清晰地表達出來，本季度我們確實看到了價格方面的影響，這主要是由於法國最終確定了醫保報銷決定。因此，本季我們對LUMAKRAS提列了1200萬美元的費用。該藥物本季銷量成長了7%。但我認為我們預料到LUMAKRAS在二線治療的應用機會只限於新發腫瘤患者。而且，我們在商業和醫療方面的規模都足以應付這項需求。我認為，隨著我們拓展到早期治療或其他腫瘤類型，我們將繼續增加對該產品的投資。

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，關於2023年的業績指引，您能否解釋一下營收成長和每股盈餘成長區間的具體計算依據是什麼？具體來說，百濟神州的會計準則是否會產生正面影響？ 18%到19%的稅率是否會對每股盈餘產生負面影響？或者，正如去年解釋的那樣，銷售成本是否會被抵銷？ 2023年的營運支出成長是否超過了營收成長？

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.

讓我們先從稅務問題著手。就稅務方面而言，18%到19%的稅率增加了PRET稅額。雖然正如我去年和今年都強調過的，我們目前在銷售成本中資本化的約1.25億美元將轉入銷售成本——抱歉，應該是轉入——主要在第一季度，但不會獲得相應的稅收優惠。因此，答案是，未來，在這1.25億美元計入銷售成本後，將大致相當於從計入銷售成本的波多黎各消費稅（PRET）降至實際所得稅稅率。

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.

關於業績指引的問題。我認為問題在於，百濟神州的哪些業務包含在內，哪些不包含在內。正如我之前回答Yaron的問題時所說，現在不會包含我們在百濟神州收益中所佔的份額，無論是損益還是虧損。因此，我們將按照市值計價的方式，在GAAP損益表中計入百濟神州的業績以及相關證券價格的變動，但不會將其計入非GAAP損益表。我們將不再記錄我們應佔的百濟神州損益。

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.

邁克爾，我先說一下，關於埃文之前的問題，如果你需要更多細節來確保你完全理解我們的回答，請告訴我們，我們會盡快回覆你。埃文，特別是你的問題，如果你不熟悉這個機制，這在法國很常見。我很樂意為你提供更多資訊。邁克爾，我知道現在事情很多，很抱歉打擾了，也不知道你之前是否看完了所有的幻燈片。所以如果你需要更多信息，請告訴我們，我們會在電話會議結束後回電給你。好的。阿文德，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。接下來是Salveen的第二個問題，您能否為我們介紹即將發表的TEPEZZA IV期臨床試驗數據及其慢性期療效背景？您希望看到哪些面向？正面的數據將如何拓展該藥物的應用前景？

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?

我們對文件內容的發言權限受到限制，您對此有何看法？

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，當然，我認為我們在這裡會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，涵蓋了患有甲狀腺眼疾（由自體免疫性甲狀腺炎引起）的患者。這項研究主要是為了收集我們認為有助於健保報銷和支付方的人群資料。接下來，我想請默多就此發表一下看法。

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?

我想指出，從機制上講，慢性甲狀腺眼疾和急性甲狀腺眼疾並無差別。事實上，慢性化只是疾病發展過程中的語義定義。但其主要由IGF1R驅動的潛在致病機制仍存在。因此，基於既往數據和機制層面，我們對這項研究持樂觀態度。 Murdo？

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。你看，我認為Horizo​​​​n團隊在產品商業化方面做得非常出色，正如Dave所提到的那樣，他們正在幫助眾多符合當前廣泛適應症的患者。而且我認為，更多的數據可能會進一步推動該產品已經非常可觀的成長。

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

好的。謝謝薩爾文的提問。我們來看下一個問題，阿文德。

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?

下一個問題來自摩根大通的克里斯多福·肖特。克里斯托弗問道：「您能否詳細介紹一下我們2023年的Otezla項目？百時美施貴寶表示，他們的過渡性藥物項目初期取得了不錯的市場反響，他們想了解這種口服藥物的市場擴張在多大程度上與Otezla的市場擴張相關？您提到未來幾個季度可能會受到無競爭對手藥物的影響。

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。這個問題和之前有人問過類似的問題，但我可以再詳細解釋一下，供克里斯參考。很明顯，皮膚科醫師在局部治療後首次嘗試全身性治療時，都希望選擇最簡單、最安全、最容易被大眾理解的產品。很多局部治療的患者都不願意嘗試全身用藥。因此，我認為Otezla的優勢就在於此。 Otezla的安全性和有效性已被充分研究，全球已有超過70萬名患者使用過該產品。

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，我們在美國獲得的一線用藥保障無需太多事先審批，這對皮膚科診所來說非常方便。這使得它成為一種非常好的首選系統性治療方案，尤其適用於病情較輕或中度的患者。對於中度或重度患者，您可能需要使用生物製劑或其他二線藥物。

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.

鑑於SOTYKTU尚未完成市場准入流程並獲得醫療保險報銷，我們認為目前還無法真正了解它在市場上的長期應用。而且我認為，有時候，這些看似不錯的專案反而會扭曲產品的實際市場接受度曲線。

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?

默多，克里斯還有第二個問題。他問的是，鑑於阿達木單抗（HUMIRA）市場價格預計大幅下跌，您如何看待恩利（ENBREL）的長期價格走勢？我知道您之前說過價格會繼續下降，但不會加速。您能否再解釋一下，為什麼在阿達木單抗市場價格大幅回落的情況下，我們不應該預期恩利的價格在2023年或2024年出現更大幅度的下跌？

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.

正如我之前提到的，我們2023年的採購週期基本上完成，並且已經確保了良好的供貨管道。正如我之前提到的，我們不得不做出一些價格上的讓步，但與往年相比，降幅並不大。所以我們對此感到滿意。恩利（ENBREL）是一款對多種適應症都非常重要的產品。

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，恩利（ENBREL）的安全性和有效性已被充分認可。我認為醫生也希望有更多選擇。我認為，藥品福利管理機構（PBM）也願意在其藥品目錄中納入多種TNF產品。我認為，這正是我們已經取得的成就，也是我們未來將繼續努力的目標。

Let's go to the next question.

我們來看下一個問題。

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莫希特·班薩爾。他的問題是，您能否詳細談談您目前為止與阿達木單抗（HUMIRA）生物相似藥的談判進展？艾伯維似乎已經與大多數競爭對手達成了價格平等協議，但上半年和下半年的定價有所不同，競爭也更加激烈。您的合約是否與之類似？隨著時間的推移，我們該如何看待上市節奏？

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.

我無法評論競爭對手與藥品福利管理機構 (PBM) 或支付方的合約。但我可以肯定的是，我們已確保 AMJEVITA 在三大全國性 PBM 獲得廣泛准入。我們將繼續與其他客戶合作，為醫療服務提供者和患者提供便利。我們將像在世界其他地區一樣，繼續憑藉該產品展開有效的競爭。在美國以外，我們憑藉 AMJEVITA 確立了領先地位。我們認為，鑑於我們提供的服務和我們的商業佈局，我們相對於其他生物相似藥而言，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.

我知道你們當中有不少人提交了問題，所以我們還在繼續處理這些問題。還沒寄email給Arvind的朋友們，我們也會一一回复，目前還有幾個問題需要解答。那麼，Arvind，我們來看下一個問題吧。

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。下一個問題來自加拿大皇家銀行資本市場（RBC Capital Markets）的格雷格·倫扎（Greg Renza），戴夫，這個問題是問你的。鑑於最近的一些交易，我們想了解貴公司在抗體藥物偶聯物（ADC）策略方面的具體情況。貴公司團隊是如何看待這個領域的？

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。我認為這只是我們工具箱中的另一種治療。過去幾年，我們一直密切關注抗體藥物偶聯物（ADC）技術。這項技術很先進，所以我們認為應該在合適的標靶上使用ADC。我認為它是我們現有治療手段的補充和擴展。

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.

這些合作將我們在標靶識別和驗證方面的經驗，以及抗體生成和一些新型偶聯技術相結合。隨著專案的推進，未來會有更多成果，但您應該將其視為我們現有技術體系的補充。

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。下一個問題來自 Wolfe Research 的 Tim Anderson。他的問題是關於美國 AMJEVITA 公司的。他想問，您對賣方對該公司 2023 年美國銷售額的普遍預期（約 6 億美元）有何評論和看法？您能否就合約細節談談，例如是否有價格保護條款，以及是否有任何合約期限超過 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，我們不提供特定產品的指導。鑑於這是首個進入美國大型藥房福利計劃的生物相似藥，這在美國生物相似藥市場也是一次全新的嘗試。因此，我們將隨著上市進程的推進，持續向大家更新資訊。我們之前說過，我們認為這次上市將是一個循序漸進的過程，我會隨時向大家報告最新情況。

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。下一個問題來自SVB Securities的Dave Risinger，他有兩個問題。第一個問題是問你的，Dave。請談談2023年值得關注的關鍵新藥候選藥物的試驗結果。第二個問題是問你的，Murdo。在AMJEVITA獲得互換性認定後，你預期它在2024年1月的藥品目錄地位可能會發生怎樣的變化？

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，David。今年，我和我的團隊的工作重點無疑是執行，因為研發管線中有很多專案需要推進。我會重點關注以下幾個面向：Olpasiran III期臨床試驗的入組情況如何？ AMG 133 II期臨床試驗的入組如何？在一般藥品產品組合中，針對發炎的rocatinlimab系列臨床試驗的入組如何？ TEZSPIRE的額外適應症進展如何？最後，在腫瘤領域，需要關注的是tarlatamab項目，不僅包括下半年可能公佈的II期註冊試驗結果，還包括啟動的二線治療III期臨床試驗。這些是我會重點關注的一些關鍵事項。當然，還有許多其他處於早期研發階段的專案和探索性​​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.

關於AMJEVITA的問題，我想說，我們致力於持續確保我們的生物相似藥的產品特性能夠為支付方、醫療服務提供者和患者帶來他們所期望的所有益處。同時，我們也努力確保長期來看，沒有理由放棄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，我們希望憑藉其互換性、高濃度以及我們已經在市場上推出了一款不含檸檬酸鹽的產品這一事實，再加上我們提供的服務，以及安進團隊非常了解該產品的炎症適應症，並且與開具 HUMIRA 處方的客戶保持著良好的關係，我們對 AMJEVITA 在 2024 年以後的長期持久性感到非常樂觀。

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公司的Umer Raffat，他有兩個問題。第一個問題是問你，Dave，關於OX40在III期臨床試驗中的每月給藥方案。他說：「我沒看到有哪個研究組會探索每季或每半年給藥一次的方案。我只是想把III期臨床試驗的給藥間隔與末次給藥後6個月內觀察到的持久療效聯繫起來。」第二個問題是問你，Peter，稅率從14%提高到18%，再到19%。我想了解一下具體情況。

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。關於羅卡汀利單抗的劑量。正如我們之前提到的，我們會探索不同的給藥方案。隨著這一系列III期臨床試驗的全面啟動，我認為，基於該分子的作用機制以及患者的用藥便利性，我們最終的目標將會更加明確。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.

Umer，關於稅收的問題問得好。再說一遍，這只是損益表上房地產項目的變化，也就是PRET從銷售成本項下移到了所得稅費用項下。這是因為波多黎各的PRET稅制從2023年開始改為實際徵收所得稅。這就是變化的本質，也是稅率從歷史水準提高到18%到19%的原因。

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公司的傑伊·奧爾森。傑伊想問的是，您能否談談安進的地域多元化計畫？過去幾個季度，安進美國以外地區的收入佔總收入的比例似乎有所下降。我們想知道是什麼潛在因素導致了這種地域結構的變化，以及未來是否有任何新產品上市或其他因素可能會促使地域結構重新傾斜到美國以外地區的成長。

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，我們對安進在全球100多個市場的國際擴張感到非常滿意。我們持續在全球推出新產品並獲得醫保報銷。我剛才提到了LUMAKRAS。最近，在中國，我們成功地為Prolia和Repatha爭取到了國家醫保報銷。我們的日本子公司發展勢頭良好。

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.

就近期而言，我認為您目前看到的現象主要是由於美國市場的產品上市時間略有提前，以及我們一些合作夥伴產品的推出。從長遠來看，我們擁有非常豐富的產品組合，這些產品將繼續走向世界。

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.

此次宣布的對Horizo​​​​n的收購在國際市場上蘊藏著巨大的機會。我們認為，從長遠來看，亞太地區實際上是我們成長最快的潛在市場。因此，我不會只關注季度間的短期波動。長期趨勢是，我們將在美國以外的地區快速成長。

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。下一個問題來自古根漢合夥公司的邁克爾·施密特，他問的是，鑑於自2020年以來Otezla的銷售額基本持平，僅為22億美元，你對2023年及以後實現兩位數低段增長有多大信心？

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的長期成長仍然充滿信心。目前市場上有許多新產品湧入，都在爭取新患者。正如我之前提到的，我認為Otezla獨特的市場定位使我們能夠獲得非常龐大的患者群體。而且，我們在全球範圍內，尤其是在美國的健保報銷覆蓋範圍，使我們能夠成功打入美國市場。因此，我們對Otezla的持續成長前景非常樂觀。

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。她問的是，從宏觀角度來看，您的業績指引暗示成長可能持平。考慮到生物相似藥和價格方面的壓力，您認為 2023 年是低谷年嗎？關於績效指引範圍，您能否說明一下生物相似藥價格波動的影響？

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.

羅賓，或許我先說最後一件事，然後皮特，你可以重申我們之前關於2023年的內容。但正如我剛才所說，羅賓，從現在到本十年末，我們計劃在美國和世界其他國家推出另外六款類似的產品。正是這些分子的陸續上市，才能讓我們繼續發展壯大這個品牌。

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.

所以我想重申一下我之前在準備好的演講稿中提到的內容。我想你們也聽到了默多談到我們認為在這裡，尤其是在AMJEVITA計畫上，將會遇到的種種誘人機遇，儘管我們才剛起步。至於2023年，皮特，我不知道你是否還有什麼補充，除了你已經提到的那些關於這一年展望的內容。

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。我想我們之前已經討論過了。我只想再次強調2022年發生的幾件事，我們預期這些事不會在2023年帶來任何利益。我們不預期2023年會有任何新冠病毒抗體收入，也不做任何假設。 Robyn，我們預期2023年Nplate的銷售額會低於2022年。回想一下，2022年下半年美國政府進行了一筆大額採購。 2022年我們還有一些有利的銷售額扣除調整，而且我們在2022年底出售了土耳其的仿製藥業務。所以，圍繞這些事件有一些利弊權衡。

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年我們的重點產品TEZSPIRE、EVENITY、Repatha、Prolia和TAVNEOS能夠實現強勁成長。同時，考慮到我們近期討論過的行業趨勢，即產品組合價格將出現個位數中段的下降，但銷量將保持良好增長，我們也應該如此。我想，回到Jay提出的問題，我們預計2023年美國以外地區的銷售量也將強勁成長。因此，我們期待以積極的姿態迎接2023年的到來。

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公司的馬特菲普斯。馬特說，2023年腫瘤生物相似藥市場指引預測，其年減幅度將達到38%，而2021年至2022年的年減幅度為30%。腫瘤生物相似藥的市佔率下降速度預計在2023年後會繼續加快，還是最終會觸底反彈？

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，這與我們迄今為止看到的平均售價下降有關。

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?

亞倫·韋伯來電。他說，稅率升至18%至19%，而銷售成本卻只有16%至17%，這讓我很困惑。因此，我在銷售成本這一項中沒有看到任何抵扣項。我到底漏掉了什麼？

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.

我認為答案在於我們的銷售成長。銷量成長相當顯著，這才是真正的抵銷因素，亞倫。問得好。我們看到這種情況正在發生。另外，關於PRET（利潤率）的下降，請記住，今年我們有1.25億美元的庫存釋放計入銷售成本，而沒有相應的稅收準備。

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，銷售額佔比與稅前利潤佔比之間的關係，也需要從所得稅準備金本身的角度來考慮。這就是其中的利弊。但歸根究底，真正將實際稅率提高到18%至19%的，是稅前利潤轉移到所得稅費用中這一環節。

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感謝您對Otezla和ENBREL的評論。能否再詳細闡述免疫學領域的動態變化？患者群體和組成是否有任何變化？藥品目錄是否有任何變動？

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.

整體而言，我們的免疫學業務前景非常樂觀。我們對TEZSPIRE的上市非常滿意。我們持續觀察到廣泛的患者表型，無論其生物標記狀態如何。我們看到一些初診患者，他們之前從未接受過生物製劑治療，目前正處於難治性氣喘的治療階段。我們也看到一些患者從同類其他產品轉用TEZSPIRE。因此，我們預期在自體免疫疾病領域，生物製劑在重度難治性氣喘治療中的應用將會不斷增長，而我們已做好充分準備，在這個不斷擴大的治療領域展開競爭。

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.

恩利（ENBREL）持續為眾多患者提供服務，其發展趨勢相當可預測且穩定。正如我們之前提到的，奧特茲拉（Otezla）正面臨來自新藥免費計畫的壓力，這不僅體現在我們的外用製劑上，也體現在新上市的口服製劑索替克妥（SOTYKTU）上。此外，我們最近也獲得了TAVNEOS的授權，我們對此感到非常興奮。 TAVNEOS是一種治療嚴重自體免疫疾病－ANCA相關性血管炎的產品。它是一款非常年輕的產品，目前仍處於生命週期的早期階段，我認為它還有很大的成長空間。

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.

當然，最後但同樣重要的是，在品牌藥方面，我們宣布收購了Horizo​​​​n公司。我認為，發炎領域，加上我們自身的創新產品線以及Horizo​​​​n的產品線，對我們來說是一個非常好的長期成長機會。最後但同樣重要的是，今天是我們推出一款新型生物相似藥的首日，這款生物相似藥是美國最暢銷的藥物——阿達木單抗（HUMIRA）的仿製藥。所以我認為，我們未來有很多成長機會。

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

我想我們只剩下最後一個問題了，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。鮑勃，讓我讀最後一個問題，之後你可能還有一些總結性評論。最後一個問題來自貝爾德公司的布萊恩‧斯科尼。布萊恩想知道，假設美國企業稅率沒有重大變化，你認為這會是一個更長期的稅率嗎？

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，Arvind？好的，Brian，我想，正如你所知，我們不提供長期稅率指導。所以我們不會透露今年以後的資訊。所以，稅率在18%到19%之間，再回到你自己的理解，確保我們明白PRET的改變。 PRET是銷售成本的百分比，而所得稅率是稅前利潤。這也是Yaron問到的一些差異。所以，今年的稅率是18%到19%，這就是我們目前能提供的資訊。

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。再次非常感謝您的耐心。很抱歉，我們供應商的網路連線在通話初期出現了一些問題。如果您還有其他問題，請聯絡 Arvind。今天下午，Peter Murdo、Dave 和我都會在線，解答您可能提出的任何問題。感謝您參加本次通話，期待在 2023 年與您繼續交流。謝謝。

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