美國安進 (AMGN) 2023 Q4 法說會逐字稿

My name is Julianne, and I will be your conference facilitator today for Amgen's Fourth Quarter 2023 Financial Results Conference Call. (Operator Instructions) I would now like to introduce Justin Claeys, Vice President of Investor Relations. Mr. Claeys, you may now begin.

我叫 Julianne，今天我將擔任安進 2023 年第四季財務業績電話會議的會議主持人。 （操作員說明） 現在我想介紹一下投資人關係副總裁 Justin Claeys。克萊斯先生，您現在可以開始了。

Thank you, Julianne. Good afternoon, and welcome to our fourth quarter 2023 earnings call. Bob Bradway will lead the call and be followed by a broader review of our performance by Murdo Gordon; Vikram Karnani; Jay Bradner, who I'm pleased to welcome and is joining us for the first time on our quarterly earnings call; and Peter Griffith. Dave Reese will also be available during the Q&A session.

謝謝你，茱麗安。下午好，歡迎參加我們的 2023 年第四季財報電話會議。鮑勃·布拉德威 (Bob Bradway) 將主持電話會議，隨後默多·戈登 (Murdo Gordon) 對我們的表現進行更廣泛的審查；維克拉姆·卡納尼； Jay Bradner，我很高興地歡迎他，他首次參加我們的季度財報電話會議；和彼得·格里菲斯。戴夫·里斯 (Dave Reese) 也將出席問答環節。

Given the timing of the Horizon Therapeutics acquisition close, the results as shown in our press release and slides include contribution from the Horizon business from October 6 onwards. For the avoidance of doubt, this will also be the basis for our filed financial results. To supplement this information, Vikram will also provide sales information for these products for the full fourth quarter, including the first week of October, as further context in his remarks. Through the course of our discussion today, we will use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompany this call. We will also make some forward-looking statements, which are qualified by our safe harbor statement. And please note that actual results can vary materially.

鑑於 Horizo​​n Therapeutics 收購完成的時間，我們的新聞稿和幻燈片中顯示的結果包括自 10 月 6 日起 Horizo​​​​n 業務的貢獻。為避免疑義，這也將成為我們提交的財務表現的基礎。為了補充這些信息，Vikram 還將提供這些產品整個第四季度的銷售信息，包括 10 月的第一周，作為他演講中的進一步背景。在今天的討論過程中，我們將使用非公認會計準則財務指標來描述我們的業績，並在本次電話會議隨附的資料中提供適當的調節。我們也將做出一些前瞻性陳述，這些陳述符合我們的安全港聲明。請注意，實際結果可能會大不相同。

With that, over to you, Bob.

就這樣，交給你了，鮑伯。

Okay. Thank you, Justin, and let me thank all of you for joining our call. 2023 was another year of performance and progress for Amgen, further positioning us to deliver attractive growth through the end of the decade and beyond. Last year, we delivered double-digit volume growth in all 4 quarters with balanced growth across products and geographies. 18 of our medicines generated record annual sales, including Repatha, Prolia, EVENITY, TEZSPIRE, BLINCYTO, KRYSTEXXA and UPLIZNA. The acquisition of Horizon, which was completed on October 6, gives us a significant new rare disease business that now stands as a fourth pillar of growth alongside our leading general medicine, oncology and inflammation businesses.

好的。謝謝賈斯汀，也謝謝大家加入我們的電話會議。 2023 年是安進業績和進步的另一年，這進一步使我們能夠在本世紀末及以後實現有吸引力的成長。去年，我們在所有 4 個季度實現了兩位數的銷售成長，並且跨產品和地理實現了均衡成長。我們的 18 種藥物創造了創紀錄的年銷售額，包括 Repatha、Prolia、EVENITY、TEZSPIRE、BLINCYTO、KRYSTEXXA 和 UPLIZNA。對Horizo​​​​n 的收購於10 月6 日完成，為我們帶來了一項重要的新罕見疾病業務，該業務現已成為我們領先的普通醫學、腫瘤學和炎症業務之外的第四個成長支柱。

The medicines we acquired are all very early in their life cycles and by leveraging Amgen's world-class biologics manufacturing, decades of experience in inflammation and our extensive global presence, we believe these products have the potential to reach many more patients around the world. Last year, we also advanced the deepest and most diverse pipeline in our history with promising molecules at all stages of development across our 4 pillars of growth. We anticipate well over a dozen significant pipeline milestones this year. I'll touch on a few.

我們所獲得的藥物均處於生命週期的早期階段，透過利用安進世界一流的生物製劑製造、數十年的發炎經驗以及我們廣泛的全球影響力，我們相信這些產品有潛力惠及世界各地更多的患者。去年，我們也推進了我們歷史上最深入、最多樣化的研發管線，在我們的四大成長支柱的各個發展階段提供有前景的分子。我們預計今年將有十多個重要的管道里程碑。我會談一些。

In general medicine, we'll generate Phase II data this year for our lead obesity molecule, MariTide, and we're excited, of course, to learn more about this asset. We're also advancing a number of early-stage assets in this space.

在普通醫學領域，我們今年將為我們的主要肥胖分子 MariTide 產生 II 期數據，當然，我們很高興了解有關該資產的更多資訊。我們也在該領域推進一些早期資產。

In oncology, we have a June 12 PDUFA date for the FDA to complete its priority review of tarlatamab as a third-line treatment for small cell lung cancer. Tarlatamab is the first bispecific T-cell engager shown to be effective in addressing a major solid tumor, in this case, one for which there has been no new treatment in decades and which today, has a 5-year survival rate of just 3%. We're studying tarlatamab in earlier lines of treatment and hope over the fullness of time to be able to serve the tens of thousands of patients diagnosed with small cell lung cancer each year in the U.S. and major markets around the world. We've done this very successfully now with our first BiTE, BLINCYTO, which has steadily moved into earlier lines of treatment for acute lymphoblastic leukemia, and we'll take the same approach with yet another promising BiTE, that being xaluritamig, in prostate cancer.

在腫瘤學方面，FDA 將於 6 月 12 日完成 PDUFA 日期，以完成 tarlatamab 作為小細胞肺癌三線治療藥物的優先審查。 Tarlatamab 是第一個被證明可有效治療主要實體瘤的雙特異性T 細胞接合劑，在這種情況下，該實體瘤幾十年來一直沒有新的治療方法，而如今，其5 年生存率僅為3% 。我們正在研究 tarlatamab 的早期治療方案，並希望在時間成熟時能夠為美國和世界主要市場每年數以萬計的被診斷患有小細胞肺癌的患者提供服務。我們現在已經透過我們的第一個BiTE BLINCYTO 非常成功地做到了這一點，它已穩步進入急性淋巴細胞白血病的早期治療領域，我們將採用相同的方法來治療前列腺癌的另一種有前途的BiTE ，即xaluritamig 。

In inflammation, we'll have Phase III data from rocatinlimab in atopic dermatitis from the first of what are now 8 trials in the ROCKET program. And in rare disease, we'll have Phase III data for UPLIZNA in myasthenia gravis and IgG4-related disease. At a time when a rapidly aging global population needs more innovation, Amgen is delivering, both with the medicines we have in the market today and with the promising new medicines that are advancing in our pipeline.

在發炎方面，我們將獲得 rocatinlimab 治療異位性皮膚炎的 III 期數據，這些數據來自 ROCKET 計畫目前 8 項試驗中的第一項試驗。在罕見疾病方面，我們將獲得 UPLIZNA 在重症肌無力和 IgG4 相關疾病中的 III 期數據。在全球人口快速老化需要更多創新之際，安進正在提供我們目前市場上現有的藥物以及我們正在開發的有前途的新藥物。

We're also excited by the rapid convergence of biotech and tech, which is enabling us to innovate more quickly and confidently. We've been preparing for this hinge moment for more than a decade and recently named Dave Reese as our first ever Chief Technology Officer to ensure that we're capitalizing on technologies like generative artificial intelligence, not just in R&D, but across the entire company. Succeeding Dave as Amgen's Head of R&D is Jay Bradner. Jay is a physician scientist and a seasoned R&D leader having served for many years as President of the Novartis Institutes for BioMedical Research. Jay previously also served as a faculty member at Harvard Medical School and, prior to joining Amgen, was a practicing oncologist at the Dana-Farber Cancer Institute. We're delighted to have Jay on board and excited by the work that he, Dave and the rest of our team will do together to accelerate innovation at Amgen for the good of patients and for the long-term growth of our business.

我們也對生物技術和技術的快速融合感到興奮，這使我們能夠更快、更自信地進行創新。十多年來，我們一直在為這一關鍵時刻做準備，最近任命 Dave Reese 為我們的首位首席技術官，以確保我們不僅在研發領域，而且在整個公司都利用生成人工智慧等技術。接替 Dave 擔任安進研發主管的是 Jay Bradner。 Jay 是一位醫師科學家和經驗豐富的研發領導者，曾擔任諾華生物醫學研究所所長多年。 Jay 先前也曾擔任哈佛醫學院的教員，在加入安進之前，曾是達納法伯癌症研究所的執業腫瘤學家。我們很高興 Jay 加入，並對他、Dave 和我們團隊其他成員將共同開展的工作感到興奮，以加速安進的創新，造福患者和我們業務的長期增長。

And with that, I want to thank our 27,000 employees around the world for their many contributions to our success. And let me now ask Murdo to talk about our commercial performance in 2023.

在此，我要感謝我們世界各地的 27,000 名員工為我們的成功做出的許多貢獻。現在請默多談談我們2023年的商業表現。

Thanks, Bob. I'm very pleased with our performance in 2023. Execution was strong across the business, resulting in record sales in the year for 18 brands and robust volume growth across the 4 pillars of our business. Full year product sales increased 9% year-over-year. Volume growth was 15% with strength across our regions. U.S. volume growth was 14%, and volume growth in our Europe, Latin America, Middle East and Canada region was 10%. Asia Pacific continues to be our fastest-growing region with 41% volume growth. These results include $954 million of sales from the legacy Horizon portfolio from the period of October 6 through December 31.

謝謝，鮑伯。我對我們 2023 年的業績感到非常滿意。整個業務的執行力強勁，導致 18 個品牌在這一年創下了創紀錄的銷售額，並在我們業務的 4 個支柱中實現了強勁的銷量增長。全年產品銷量較去年同期成長9%。我們各地區的銷量成長了 15%。美國銷量成長 14%，歐洲、拉丁美洲、中東和加拿大地區銷量成長 10%。亞太地區仍然是我們成長最快的地區，銷量成長了 41%。這些業績包括 10 月 6 日至 12 月 31 日期間傳統 Horizo​​n 產品組合的 9.54 億美元銷售額。

I'll start with our general medicine business, which includes Repatha, Prolia, EVENITY and Aimovig. Overall revenue for these 4 products grew 15% year-over-year in the fourth quarter and 17% for the full year driven by 18% and 20% volume growth, respectively. Repatha sales increased 25% year-over-year in the fourth quarter with volume growth of 35% partially offset by lower net selling price. Outside of the U.S., we saw 25% volume growth with strength across our regions.

我將從我們的普通藥品業務開始，其中包括 Repatha、Prolia、EVENITY 和 Aimovig。在銷量成長 18% 和 20% 的推動下，這 4 種產品的總收入在第四季度同比增長 15%，全年同比增長 17%。第四季 Repatha 銷售額年增 25%，銷售成長 35%，部分被淨售價下降抵銷。在美國以外的地區，我們的銷量成長了 25%，且表現強勁。

In the U.S., volume growth of 48% was driven by a 66% increase in the number of new patients starting treatment. We saw a decline in net selling price in the U.S. primarily driven by new formulary coverage. We expect this additional coverage to lead to strong volume growth, which will more than offset declining net selling price. In addition, some payers have recently removed prior authorization for some patients, which will further ease their access to Repatha.

在美國，開始治療的新患者數量增加了 66%，推動了治療量增加 48%。我們看到美國淨售價的下降主要是由於新處方覆蓋範圍的推動。我們預計這種額外的覆蓋範圍將導致銷售強勁成長，這將足以抵消淨售價的下降。此外，一些付款人最近取消了對部分患者的事先授權，這將進一步方便他們使用 Repatha。

We remain committed to the urgent need to educate physicians and patients on the importance of LDL-C lowering to reduce the risk of cardiovascular events. In the U.S., we activated more than 20,000 new prescribing physicians in 2023 in both the primary care and cardiology settings. And while we're pleased with this progress, we'll continue to work tirelessly for the many, many more patients around the world who can benefit from Repatha.

我們仍然致力於迫切需要教育醫生和患者降低 LDL-C 以降低心血管事件風險的重要性。在美國，我們於 2023 年在初級保健和心臟病學領域啟用了 20,000 多名新處方醫生。雖然我們對這項進展感到滿意，但我們將繼續不懈地努力，讓世界各地更多的患者能夠從 Repatha 中受益。

Transitioning to bone health. EVENITY had record sales of $318 million for the quarter driven by 39% volume growth. Osteoporosis disproportionately impacts postmenopausal women, and the diagnosis and treatment rates for these patients are low. In the U.S., only 6% of very high risk patients with osteoporosis are treated with a bone builder, creating an urgent need for treatment with an effective therapy. EVENITY is an important therapy to address this unmet need as it is the only bone builder that works with the body's natural ability to increase bone formation and also decrease bone resorption. We see strong growth potential for EVENITY, and we'll continue to apply our proven experience in bone health to ensure it reaches all the patients who need it.

過渡到骨骼健康。在銷售成長 39% 的推動下，EVENITY 本季銷售額達到創紀錄的 3.18 億美元。骨質疏鬆症對停經後婦女的影響尤其嚴重，而這些患者的診斷和治療率很低。在美國，只有 6% 的骨質疏鬆症高風險患者接受了骨生成劑治療，因此迫切需要有效的治療方法。 EVENITY 是解決這項未滿足需求的重要療法，因為它是唯一一種能夠與人體自然能力一起增加骨形成並減少骨吸收的成骨劑。我們看到 EVENITY 的強勁成長潛力，我們將繼續運用我們在骨骼健康方面經過驗證的經驗，確保它惠及所有需要它的患者。

Prolia sales grew 12% year-over-year to a record $1.1 billion for the fourth quarter. Volume growth of 10% was supported by real-world evidence reaffirming Prolia's superiority in reducing fracture risk when compared to alendronate in treatment-naive patients with postmenopausal osteoporosis at a high risk of fracture.

Prolia 第四季銷售額年增 12%，達到創紀錄的 11 億美元。現實世界的證據支持了 10% 的體積增長，再次證實了對於骨折風險較高的停經後骨質疏鬆症初治患者，與阿崙膦酸鈉相比，Prolia 在降低骨折風險方面具有優越性。

Moving to our oncology business, which includes BLINCYTO, LUMAKRAS, Vectibix, KYPROLIS, Nplate and XGEVA. Sales of these 6 innovative products grew 5% year-over-year for the fourth quarter with 3% volume growth. Full year sales grew 12% year-over-year driven by 12% volume growth. BLINCYTO sales grew 47% year-over-year to a record $241 million for the fourth quarter. Volume growth of 55% was supported by broad prescribing to patients with acute lymphoblastic leukemia in frontline consolidation treatment. Long term, we see significant growth potential for BLINCYTO from utilization earlier in the front line as part of induction treatment.

轉向我們的腫瘤業務，包括 BLINCYTO、LUMAKRAS、Vectibix、KYPROLIS、Nplate 和 XGEVA。第四季這 6 種創新產品的銷售額年增 5%，銷量成長 3%。在銷量成長 12% 的推動下，全年銷售額較去年同期成長 12%。 BLINCYTO 第四季銷售額年增 47%，達到創紀錄的 2.41 億美元。 55% 的銷售量成長得益於一線鞏固治療中對急性淋巴性白血病患者的廣泛處方。從長遠來看，我們認為 BLINCYTO 在第一線早期使用作為誘導治療的一部分具有巨大的成長潛力。

LUMAKRAS sales increased 8% year-over-year for the fourth quarter. We see future growth opportunities for LUMAKRAS coming from launches in new markets and additional indications. Vectibix sales increased 5%, and KYPROLIS sales grew 8% year-over-year for the fourth quarter, both driven by volume growth.

LUMAKRAS 第四季銷售額年增 8%。我們認為 LUMAKRAS 未來的成長機會來自於新市場的推出和其他適應症。第四季 Vectibix 銷售額年增 5%，KYPROLIS 銷售額年增 8%，兩者均受到銷量成長的推動。

Nplate sales decreased 18% year-over-year for the fourth quarter, driven by volume decline related to timing of orders placed by the U.S. government, partially offset by volume growth across our regions. Full year sales increased 13%, primarily driven by volume growth, including U.S. government orders. Excluding U.S. government orders, Nplate sales grew 23% year-over-year for the fourth quarter and 8% for the full year.

第四季 Nplate 銷售額年減 18%，因為與美國政府下訂單時間相關的銷售量下降，但部分被我們各地區的銷售成長所抵銷。全年銷售額成長 13%，主要受到銷售成長的推動，其中包括美國政府訂單。不包括美國政府訂單，Nplate第四季銷售額年增23%，全年成長8%。

Transitioning to our inflammation business. Otezla sales increased 2% year-over-year for the fourth quarter, driven by favorable changes to estimated sales deductions and 3% volume growth, partially offset by lower inventory levels and lower net selling price. Full year sales decreased 4% driven by lower net selling price and lower inventory levels partially offset by 2% volume growth. New patient starts for Otezla grew 6% in the fourth quarter driven by strong execution and increased investment. Competitor free drug programs had a reduced impact in the quarter. Otezla is uniquely positioned to grow in 2024 and beyond, given its indication for all severities of psoriasis, combined with an established clinical profile, broad payer coverage, a lack of testing required for initiation and convenient oral administration.

轉向我們的炎症業務。由於預計銷售扣除額的有利變化和 3% 的銷量增長，第四季度 Otezla 銷售額同比增長 2%，但庫存水平下降和淨售價下降部分抵消了這一影響。由於淨售價下降和庫存水準下降，全年銷售額下降 4%，但銷量成長 2% 部分抵消了這一影響。在強勁的執行力和投資增加的推動下，Otezla 第四季度的新患者數量增加了 6%。無競爭對手藥物計劃在本季的影響力有所減弱。鑑於Otezla 適用於所有嚴重程度的乾癬，加上既定的臨床特徵、廣泛的支付者覆蓋範圍、缺乏啟動所需的測試以及方便的口服給藥，Otezla 具有獨特的優勢，可以在2024 年及以後實現成長。

Enbrel sales decreased 8% year-over-year for the fourth quarter driven by a 4% impact from unfavorable changes to estimated sales deductions and lower net selling price. U.S. volume grew 1% in the fourth quarter, supported by an increase in new patients starting treatment as a result of improved payer coverage. Going forward, we expect net selling price to continue to decline year-over-year driven by higher rebates to maintain broad first-line payer coverage and changes in patient mix.

Enbrel 第四季銷售額年減 8%，這是由於預期銷售扣除額的不利變化和淨售價下降造成 4% 的影響。由於付款人覆蓋範圍的改善，開始接受治療的新患者數量增加，第四季度美國的治療量增加了 1%。展望未來，我們預計淨售價將繼續同比下降，原因是回扣較高，以維持廣泛的一線支付者覆蓋範圍和患者結構的變化。

TEZSPIRE continues a strong launch trajectory with $177 million in sales in the fourth quarter and $567 million for the full year. Sales increased 10% sequentially driven by volume growth. Our successful launch of a self-administered, prefilled, single-use pen allowed us to expand coverage with major pharmacy benefit managers to over 80%, contributing to higher new patient growth as the year progressed. Moving forward, we expect this expanded coverage will allow TEZSPIRE to help even more patients with severe uncontrolled asthma.

TEZSPIRE 持續保持強勁的推出軌跡，第四季銷售額為 1.77 億美元，全年銷售額為 5.67 億美元。由於銷量成長，銷售額較上季成長 10%。我們成功推出了自我管理、預先填充、一次性使用筆，使我們能夠將主要藥品福利管理機構的覆蓋率擴大到80% 以上，從而隨著時間的推移，為新患者的成長做出了更大的貢獻。展望未來，我們預計擴大的覆蓋範圍將使 TEZSPIRE 能夠幫助更多患有嚴重不受控制的氣喘的患者。

Sales of TAVNEOS were $44 million in the quarter and $134 million for the full year. In the fourth quarter, we saw 17% quarter-over-quarter volume growth in the U.S. Approximately 2,700 patients have now been treated with TAVNEOS by over 1,700 health care professionals. Looking forward, we will continue to leverage our expertise in nephrology and inflammation to bring TAVNEOS to even more patients with ANCA-associated vasculitis.

TAVNEOS 本季銷售額為 4,400 萬美元，全年銷售額為 1.34 億美元。第四季度，我們在美國的銷售量較上季成長了 17%。現在有超過 1,700 名醫療保健專業人員接受了 TAVNEOS 治療，約 2,700 名患者。展望未來，我們將繼續利用我們在腎臟病學和發炎方面的專業知識，將 TAVNEOS 帶給更多 ANCA 相關血管炎患者。

Sales for our biosimilars portfolio grew 10% year-over-year for the fourth quarter and 5% for the full year driven by 27% and 29% volume growth. This volume growth was partially offset by net selling price decline. Over time, we expect long-term growth in our biosimilars business to be driven by the addition of new molecules and additional launches.

在銷量成長 27% 和 29% 的推動下，我們的生物相似藥組合銷售額第四季年增 10%，全年年增 5%。銷量成長被淨售價下降部分抵銷。隨著時間的推移，我們預計我們的生物相似藥業務的長期成長將由新分子的添加和更多產品的推出推動。

Overall, our execution is strong across the business, underscored by our foundational commitment to serve patients. The 4 pillars of our portfolio position us well to serve many more patients around the world who can benefit from our innovative therapies.

整體而言，我們整個業務的執行力很強，這體現在我們為病患服務的基本承諾上。我們產品組合的四大支柱使我們能夠為世界各地更多可以從我們的創新療法中受益的患者提供服務。

And with that, I'll turn it over to Vikram, who will cover our rare disease portfolio.

接下來，我會將其交給 Vikram，他將負責我們的罕見疾病組合。

Thanks, Murdo. I am glad to share an update on our rare disease business now that we are 4 months past due close. We are now fully operating as part of Amgen with integration activities ongoing. As Bob has mentioned before, we are excited to be Amgen's fourth pillar of long-term growth. I wanted to make sure you're aware that we are not reporting the full quarter in press release and slides, which reflects sales from October 6 onwards and total $954 million. This excludes $41 million of sales that occurred in the first week of October prior to deal close. For the full quarter, our rare disease brands from Horizon delivered product sales of $995 million, representing 6% year-over-year sales growth. Throughout the remainder of my remarks, I will reference full quarter product sales.

謝謝，默多。我很高興與大家分享我們罕見疾病業務的最新情況，現在我們已經逾期 4 個月了。我們現在作為安進的一部分全面運營，整合活動正在進行中。正如鮑伯之前提到的，我們很高興成為安進長期成長的第四個支柱。我想確保您知道，我們不會在新聞稿和幻燈片中報告整個季度的情況，這反映了 10 月 6 日以來的銷售額，總計 9.54 億美元。這不包括 10 月第一週交易完成前 4,100 萬美元的銷售額。整個季度，我們的 Horizo​​n 罕見疾病品牌產品銷售額達到 9.95 億美元，年成長 6%。在我接下來的發言中，我將提及整個季度的產品銷售情況。

TEPEZZA and IGF-1R monoclonal antibody for patients with thyroid eye disease generated $467 million of sales during the entire fourth quarter, representing 3% quarter-over-quarter growth. This is the third quarter in a row of quarter-over-quarter growth for TEPEZZA with the growth largely driven by the U.S. We saw a number of positive leading indicators, including a record number of unique TEPEZZA prescribers, total patient enrollment forms and patient starts in 2023. Additionally, thanks to our efforts, we've been able to generate favorable medical policy changes for greater than 50% of U.S. covered lives, and we expect to continue this momentum throughout 2024.

用於治療甲狀腺眼疾患者的 TEPEZZA 和 IGF-1R 單株抗體在整個第四季度創造了 4.67 億美元的銷售額，環比成長 3%。這是 TEPEZZA 連續第三個季度實現環比增長，增長主要由美國推動。我們看到了許多積極的領先指標，包括創紀錄的 TEPEZZA 處方醫生數量、患者登記表總數和患者起始人數2023 年。此外，由於我們的努力，我們已經能夠為超過50% 的美國受保人帶來有利的醫療政策變化，我們預計在2024 年將繼續保持這一勢頭。

We continue to see approximately 100,000 patients with moderate to severe disease in the U.S. who could benefit from TEPEZZA, with the majority of these patients in low clinical activity score settings. Given positive leading indicators and high unmet need, we see a long-term growth opportunity for TEPEZZA in the U.S. while also recognizing there is some time lag between our execution efforts and the realization of increased patient numbers.

我們繼續看到美國大約 100,000 名患有中度至重度疾病的患者可以從 TEPEZZA 中受益，其中大多數患者的臨床活動評分較低。鑑於積極的領先指標和較高的未滿足需求，我們看到 TEPEZZA 在美國的長期成長機會，同時也認識到我們的執行努力和實現患者數量增加之間存在一定的時間滯後。

International expansion also remains a meaningful long-term growth opportunity for TEPEZZA. TEPEZZA is approved in Brazil, and we are progressing towards approval in additional countries. Our expansion into both Japan and Europe is a high priority with regulatory review underway in Japan and filings in the EU throughout the year.

國際擴張對於 TEPEZZA 來說仍然是一個有意義的長期成長機會。 TEPEZZA 在巴西獲得批准，我們正在努力爭取在其他國家獲得批准。我們向日本和歐洲的擴張是我們的首要任務，全年將在日本進行監管審查並在歐盟進行備案。

KRYSTEXXA, a pegylated uricase enzyme for patients with chronic refractory gout, delivered a record $280 million in sales for the entire fourth quarter, representing 30% year-over-year growth, driven by continued strong commercial execution. Sales are now annualizing $1 billion run rate. Performance was driven by execution across all phases of the patient journey, demand generation, stakeholder engagement and adherence to treatment.

KRYSTEXXA 是一種治療慢性難治性痛風患者的聚乙二醇化尿酸酶，在持續強勁的商業執行力的推動下，整個第四季度的銷售額達到創紀錄的 2.8 億美元，同比增長 30%。目前年銷售額為 10 億美元。績效是由病人旅程所有階段的執行、需求產生、利害關係人參與和堅持治療所驅動的。

UPLIZNA, an anti-CD19 monoclonal antibody, which is now the fastest-growing biologic in NMOSD, delivered a record $70 million in sales for the entire fourth quarter, representing 68% year-over-year growth. International expansion is also underway with UPLIZNA now launched in multiple ex U.S. markets.

UPLIZNA 是一種抗 CD19 單株抗體，目前是 NMOSD 中成長最快的生物製劑，整個第四季的銷售額達到創紀錄的 7,000 萬美元，年成長 68%。國際擴張也正在進行中，UPLIZNA 現已在美國以外的多個市場推出。

Our remaining ultra rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra rare medicines, RAVICTI, PROCYSBI and ACTIMMUNE. Looking ahead at 2024, by leveraging Amgen's world-class biologics capabilities, decades of experience in inflammation and extensive global presence, we are ready to reach more patients than ever before.

我們剩餘的超稀有藥物組合在整個第四季度創造了 1.78 億美元的銷售額，這主要是由我們的超稀有藥物 RAVICTI、PROCYSBI 和 ACTIMMUNE 推動的。展望 2024 年，透過利用安進世界一流的生物製劑能力、數十年的發炎經驗和廣泛的全球影響力，我們已準備好接觸比以往更多的患者。

I will now turn it over to Jay.

我現在將把它交給傑伊。

Thank you, Vikram, and good afternoon, everyone. I'd like to take a minute to convey how thrilled I am to join the Amgen R&D organization and this leadership team. The creativity of our discovery research, expert and expedited clinical development, most authoritative biomanufacturing organization in the industry, all were well known to me before joining. But now on staff at Amgen, I appreciate the strong sense of service to patients facing serious illness, the like-minded commitment, growing the impact of our medicines and our business and the shared conviction in this remarkable portfolio of potential first-in-class and best-in-class medicines.

謝謝維克拉姆，大家下午好。我想花一點時間表達我對加入安進研發組織和這個領導團隊感到多麼興奮。我們的發現研究的創造力、專家和快速的臨床開發、業內最權威的生物製造組織，這些都是我在加入之前就熟知的。但現在作為安進的員工，我很欣賞他們為面臨嚴重疾病的患者提供的強烈服務意識、志同道合的承諾、不斷擴大的我們藥品和業務的影響力以及對這一卓越的潛在一流產品組合的共同信念。和一流的藥物。

In 2023, we executed with speed across our clinical pipeline, achieving excellent enrollment in key programs and setting up 2024 as the year with significant data readouts across the portfolio for medicines with the potential to transform patient care. Key highlights in 2023 included the delivery of promising data from 4 key oncology assets and the attainment of 3 breakthrough therapy designations in oncology. We initiated pivotal Phase III studies for tarlatamab in small cell lung cancer, LUMAKRAS in non-small cell lung cancer and colorectal cancer, along with dazodalibep in Sjögren's syndrome. In general medicine, as previously disclosed, top line 52-week data from the 592-patient MariTide Phase II study is expected by late 2024. Leveraging the durability of weight loss observed in Phase I and rapid enrollment enjoyed in Phase II, we recently added a part 2 to this study, which explores durable weight loss beyond 52 weeks. Our planning for a comprehensive Phase III program across multiple indications remains on track.

2023 年，我們在整個臨床管道中快速執行，在關鍵項目中實現了出色的入組率，並將2024 年定為在整個藥物組合中獲得大量數據的一年，這些藥物具有改變患者護理的潛力。 2023 年的主要亮點包括提供來自 4 個關鍵腫瘤學資產的有希望的數據以及獲得 3 個腫瘤學突破性治療指定。我們啟動了 tarlatamab 治療小細胞肺癌、LUMAKRAS 治療非小細胞肺癌和結直腸癌以及 dazodalibep 治療乾燥綜合徵的關鍵 III 期研究。在普通醫學方面，正如先前披露的，預計到2024 年末，來自592 名患者的MariTide II 期研究的52 週頂線數據。利用I 期觀察到的體重減輕的持久性和II 期的快速入組，我們最近補充道本研究的第二部分，探討 52 週以上的持久減肥效果。我們針對多種適應症的全面 III 期計劃的規劃仍在按計劃進行。

Lastly, you may have seen that yesterday, Nature Metabolism published a manuscript from Amgen R&D that provides the integration of MariTide preclinical and Phase I data. Beyond MariTide, our obesity strategy encompasses several assets with AMG 786 in Phase I and additional preclinical assets advancing. Our approach is tailored to meet the dynamic needs of obesity treatment, demonstrating a longitudinal commitment to innovation and patient care in this field.

最後，您可能已經看到，昨天，Nature Metabolism 發表了一份來自安進研發部的手稿，其中提供了 MariTide 臨床前和 I 期數據的整合。除了 MariTide 之外，我們的肥胖策略還包括處於 I 期的 AMG 786 等多項資產以及正在推進的其他臨床前資產。我們的方法是為滿足肥胖治療的動態需求而量身定制的，展示了對該領域創新和患者護理的長期承諾。

The Phase III outcome study of olpasiran, our potentially best-in-class Lp(a) targeting small interfering RNA molecule in atherosclerotic cardiovascular disease, has enrolled more than 7,000 patients globally. This rapid enrollment accomplished in just 1 year across 34 countries and over 700 sites underscores the medical community's strong interest in and the potential impact of olpasiran. We've deliberately expanded our initial enrollment target from 6,000 to over 7,000 patients to ensure comprehensive demographic representation and to satisfy regional regulatory requirements. We are on track to complete enrollment in the first half of 2024.

olpasiran 是我們潛在的同類最佳 Lp(a)，針對動脈粥狀硬化性心血管疾病中的小幹擾 RNA 分子，其 III 期結果研究已在全球招募了 7,000 多名患者。短短一年內在 34 個國家和 700 多個地點完成的快速入組突顯了醫學界對 olpasiran 的強烈興趣及其潛在影響。我們有意將最初的入組目標從 6,000 名患者擴大到 7,000 多名患者，以確保全面的人口代表性並滿足地區監管要求。我們預計在 2024 年上半年完成註冊。

In oncology, we're focused on approaching high conviction targets with differentiated therapies for large effect sizes. We're pleased to announce that the FDA granted priority review for BLINCYTO in early-stage CD19-positive B-ALL with a PDUFA date of June 21, 2024. The ongoing Phase III Golden Gate study is enrolling patients to evaluate the effectiveness of alternating BLINCYTO with low-intensity chemotherapy curing older adults diagnosed with Philadelphia chromosome-negative B-ALL. We're also planning to amend this study to evaluate subcutaneous administration of blinatumomab with initiation anticipated in the second half of 2024, potentially allowing us to serve more patients and treating physicians.

在腫瘤學領域，我們專注於透過差異化療法實現大效果的高可信度目標。我們很高興地宣布，FDA 授予BLINCYTO 治療早期CD19 陽性B-ALL 的優先審查資格，PDUFA 日期為2024 年6 月21 日。正在進行的III 期Golden Gate 研究正在招募患者，以評估交替治療的有效性BLI​​NCYTO 與低強度化療可治癒診斷為費城染色體陰性 B-ALL 的老年人。我們還計劃修改這項研究，以評估 blinatumomab 的皮下給藥，預計於 2024 年下半年啟動，這可能使我們能夠為更多患者和治療醫生提供服務。

Lastly, we're pleased to announce that just today, the American Journal of Hematology published a manuscript highlighting data from the dose expansion phase of our ongoing Phase Ib study of subcutaneous blinatumomab as a single agent in adult patients with heavily pretreated relapsed/refractory B-cell ALL. Of 27 evaluable patients treated, we observed an 85% complete response rate, of which 75% were MRD negative. Subcutaneous blinatumomab was well tolerated with no observed grade 4 cytokine release syndrome.

最後，我們很高興地宣布，就在今天，《美國血液學雜誌》發表了一份手稿，重點介紹了我們正在進行的Ib 期皮下注射blinatumomab 作為單藥治療患有經過大量治療的複發/難治性B 期成人患者的劑量擴展階段的數據-細胞全部。在接受治療的 27 名可評估患者中，我們觀察到 85% 的完全緩解率，其中 75% 的 MRD 陰性。皮下注射 blinatumomab 耐受性良好，未觀察到 4 級細胞激素釋放症候群。

Turning to tarlatamab, a first-in-class DLL3 targeting BiTE molecule. The FDA granted priority review following promising results from the Phase II DeLLphi-301 clinical trial and a PDUFA date of June 12, 2024. We are rapidly advancing tarlatamab into earlier lines of treatment, where we have initiated 2 Phase III studies and plan to initiate a third in the first half of 2024.

轉向 tarlatamab，一種一流的 DLL3 靶向 BiTE 分子。在II 期DeLLphi-301 臨床試驗取得可喜的結果以及PDUFA 日期為2024 年6 月12 日之後，FDA 授予了優先審查權。我們正在迅速將tarlatamab 推進到早期治療領域，我們已經啟動了2 項III 期研究，並計劃啟動2024 年上半年將達到三分之一。

Xaluritamig, a first-in-class STEAP1 bispecific molecule being studied in metastatic castrate-resistant prostate cancer, continues to progress following the presentation of encouraging Phase I data last fall. We are ahead of schedule with the monotherapy dose expansion and expect to complete enrollment in the coming weeks. We've opened a reduced monitoring cohort and are making significant progress in dose range finding studies in combination with novel hormonal therapy combinations.

Xaluritamig 是一種一流的 STEAP1 雙特異性分子，正在研究治療轉移性去勢抵抗性前列腺癌，繼去年秋天公佈令人鼓舞的 I 期數據後，該藥物繼續取得進展。我們提前完成了單藥治療劑量的擴大，並預計在未來幾週內完成入組。我們已經減少了監測隊列，並在與新型激素治療組合相結合的劑量範圍尋找研究方面取得了重大進展。

For AMG 193, an oral MTA-cooperative PRMT5 inhibitor, we're encouraged by 9 responses we've seen across 7 MTAP-null solid tumors. AMG 193 is a terrific example of a medicine targeting a genetically-defined synthetic lethality and a first clinical translation of our induced proximity platform. We're now swiftly moving forward with dose expansion studies and plan to enter master protocols in thoracic and gastrointestinal malignancies, exploring combinations with standard of care in the first half of 2024.

對於 AMG 193（一種口服 MTA 協同 PRMT5 抑制劑），我們在 7 個 MTAP 無效的實體瘤中看到了 9 種反應，這讓我們深受鼓舞。 AMG 193 是針對基因定義的合成致死性的藥物的一個很好的例子，也是我們誘導接近平台的首次臨床轉化。我們現在正在迅速推進劑量擴展研究，並計劃在 2024 年上半年制定胸部和胃腸道惡性腫瘤的主方案，探索與標準護理的組合。

In our inflammation portfolio, we continue to explore TEZSPIRE in indications beyond severe asthma, including separate Phase III studies in chronic rhinosinusitis with nasal polyps, where top line data are expected in the second half of 2024, as well as in eosinophilic esophagitis. We also remain on track to present Phase II COPD data in the first half of 2024.

在我們的發炎產品組合中，我們繼續探索TEZSPIRE 的嚴重氣喘以外的適應症，包括慢性鼻竇炎伴鼻息肉的獨立III 期研究（預計將於2024 年下半年獲得一線數據）以及嗜酸性粒細胞性食道炎。我們也將繼續在 2024 年上半年提供第二階段 COPD 數據。

Our ROCKET Phase III program for rocatinlimab, a first-in-class anti-OX40 monoclonal antibody, has successfully enrolled over 2,400 patients with moderate to severe atopic dermatitis. We're introducing an eighth study to the ROCKET program to explore an auto-injector, and we are planning to initiate both the Phase III study in prurigo nodularis and a Phase II study in asthma this year as we seek to broadly explore the potential of rocatinlimab.

我們的 ROCKET III 期計畫 rocatinlimab（一種一流的抗 OX40 單株抗體）已成功入組 2,400 多名中度至重度異位性皮膚炎患者。我們正在向 ROCKET 計劃引入第八項研究，以探索自動注射器，並且我們計劃今年啟動結節性癢疹的 III 期研究和哮喘的 II 期研究，因為我們尋求廣泛探索自動注射器的潛力羅卡廷利馬布。

Lastly, we are encouraged by the advancements of our rare disease pipeline with several mid- to late-stage opportunities. In December, TEPEZZA received orphan drug designation in Japan, where we've also recently submitted a new drug application for TEPEZZA in thyroid eye disease. To serve additional patients in Japan, we have a Phase III study underway in the setting of chronic disease with a low clinical activity score. Beyond Japan, we are progressing TEPEZZA subcutaneous administration to drive increased adoption and improve patient experience and plan to initiate a Phase III study in thyroid eye disease this year.

最後，我們對罕見疾病產品線的進步以及一些中後期機會感到鼓舞。 12 月，TEPEZZA 在日本獲得孤兒藥資格認定，我們最近也在日本提交了 TEPEZZA 治療甲狀腺眼疾的新藥申請。為了為日本的更多患者提供服務，我們正在進行一項針對臨床活動評分較低的慢性病的 III 期研究。在日本以外，我們正在推進 TEPEZZA 皮下給藥，以推動更多採用並改善患者體驗，並計劃今年啟動甲狀腺眼病的 III 期研究。

With UPLIZNA, we anticipate important Phase III data readouts this year in myasthenia gravis and IgG4-related disease, both diseases with significant unmet need and where we have the potential to make a real difference for patients. Dazodalibep, an innovative CD40 ligand inhibitor fusion protein, has entered Phase III for Sjögren's syndrome. This follows encouraging Phase II data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden. Dazodalibep is the first therapy to demonstrate efficacy in this latter patient population. Closing out our rare disease efforts, we're excited about fipaxalparant, an LPAR1 antagonist being studied in idiopathic pulmonary fibrosis, on track for a Phase II proof-of-concept data readout in the second half of 2024.

透過 UPLIZNA，我們預計今年將獲得重症肌無力和 IgG4 相關疾病的重要 III 期數據，這兩種疾病的需求顯著未得到滿足，並且我們有潛力為患者帶來真正的改變。 Dazodalibep 是一種創新的 CD40 配體抑制劑融合蛋白，已進入治療乾燥症的 III 期臨床。在此先前的第二階段數據令人鼓舞，該數據對中度至重度全身性疾病患者和高症狀負擔患者有效。 Dazodalibep 是第一個在後一類患者群體中顯示出療效的療法。結束我們在罕見疾病方面的工作後，我們對 fipaxalparant 感到興奮，它是一種正在研究特發性肺纖維化的 LPAR1 拮抗劑，預計在 2024 年下半年公佈 II 期概念驗證數據。

In closing, I'm delighted to report on the important progress we made advancing our innovative pipeline, and I'm looking forward to sharing more pipeline milestones through 2024. I'll now turn it over to you, Peter.

最後，我很高興地報告我們在推進創新管道方面取得的重要進展，我期待著分享到 2024 年的更多管道里程碑。現在我將把它交給你，Peter。

Thank you, Jay. We're pleased with our strong execution and performance in the fourth quarter and for the full year 2023. In the fourth quarter, total revenue of $8.2 billion grew 20% year-over-year and non-GAAP EPS of $4.71 grew 15% year-over-year. For the full year, we delivered total revenue of $28.2 billion, 7% growth year-over-year, and non-GAAP EPS of $18.65, 5% growth year-over-year. As a reminder, both Q4 and the full year results include Horizon's results beginning October 6, when the acquisition closed, so our financial results will exclude approximately 1 week of Horizon's results from our fourth quarter results. I'll review the details of our fourth quarter and full year financial results before discussing our outlook for 2024. The financial results are shown on Slides 54 to 56 of the slide deck.

謝謝你，傑伊。我們對第四季和 2023 年全年的強勁執行力和業績感到滿意。第四季總營收為 82 億美元，年增 20%，非 GAAP 每股收益為 4.71 美元，年增 15% -同比。全年總收入為 282 億美元，年增 7%，非 GAAP 每股收益為 18.65 美元，年增 5%。提醒一下，第四季度和全年業績都包括Horizo​​​​n 自10 月6 日（收購結束時）開始的業績，因此我們的財務業績將從第四季度業績中排除Horizo​​​​n 大約1 週的業績。在討論我們對 2024 年的展望之前，我將回顧我們第四季和全年財務表現的詳細資訊。財務表現顯示在投影片的第 54 至 56 張投影片中。

Turning to our fourth quarter total revenue of $8.2 billion. We saw product sales increase 20% year-over-year, driven by volume growth of 23%, offset by net selling price decline of 3%. Excluding the impact of Horizon, product sales increased 5% year-over-year driven by volume growth of 9%. Full year total revenues of $28.2 billion grew 7% year-over-year. Product sales increased 9% year-over-year driven by 15% volume growth. Other revenues decreased 16% year-over-year primarily due to lower profit and cost sharing from our COVID-19 collaboration with Lilly in 2022.

轉向我們第四季 82 億美元的總營收。我們看到，在銷量成長 23% 的推動下，產品銷量年增 20%，但被淨售價下降 3% 所抵銷。排除 Horizo​​n 的影響，在銷量成長 9% 的推動下，產品銷售額年增 5%。全年總收入為 282 億美元，年增 7%。在銷量成長 15% 的推動下，產品銷售額較去年同期成長 9%。其他收入較去年同期下降 16%，主要是由於 2022 年我們與禮來公司 (Lilly) 合作的 COVID-19 合作帶來的利潤和成本分攤減少。

Strong expense discipline resulted in a 50% non-GAAP operating margin as a percentage of product sales for the full year 2023 while we continued to focus on both internal and external innovation, investing $4.7 billion in our pipeline and $27.8 billion in our acquisition of Horizon. With product sales volume growth at 23% in Q4 and 15% for the full year, we still efficiently managed the operating expenses of the business, Q4 non-GAAP operating expenses increasing 18% year-over-year while full year non-GAAP operating expenses increased 9%.

嚴格的費用紀律使得2023 年全年的非GAAP 營運利潤率佔產品銷售額的百分比達到50%，同時我們繼續專注於內部和外部創新，在管道上投資47 億美元，在收購Horizo​​​​n 上投資278 億美元。在第四季度和全年產品銷售增加 23% 和 15% 的情況下，我們仍然有效地管理了業務的營運費用，第四季度非 GAAP 營運費用年增 18%，而全年非 GAAP 營運費用開支增加了9%。

Excluding the impact of Horizon, Q4 non-GAAP operating expenses increased 3% and full year non-GAAP operating expenses increased 5%. On a non-GAAP basis, Q4 cost of sales as a percentage of product sales was flat on a year-over-year basis at 16.3%. For the full year, cost of sales as a percentage of product sales increased by 1.1 percentage points to 17.0%. The full year increase was primarily driven by higher profit share and changes in our product mix partially offset by the replacement of the Puerto Rico excise tax with an income tax beginning in 2023. Non-GAAP R&D spend in the fourth quarter increased 16% year-over-year and 8% year-over-year for the full year primarily due to higher spend on later-stage clinical programs and marketed product support, including spend on programs acquired from the Horizon acquisition and continuing investment in our pipeline, including MariTide.

排除 Horizo​​n 的影響，第四季度非 GAAP 營運費用增加 3%，全年非 GAAP 營運費用增加 5%。以非公認會計準則計算，第四季銷售成本佔產品銷售額的百分比與去年同期持平，為 16.3%。全年銷售成本佔產品銷售額的比例上升1.1個百分點至17.0%。全年成長主要是由於利潤份額的提高以及我們產品組合的變化，部分被從 2023 年開始用所得稅取代波多黎各消費稅所抵消。第四季度的非 GAAP 研發支出同比增長 16%同比增長8%，全年年比成長8%，主要是由於後期臨床項目和上市產品支援的支出增加，包括從Horizo​​​​n 收購中獲得的項目支出以及對我們的管道（包括MariTide）的持續投資。

Q4 non-GAAP SG&A expenses increased 20% year-over-year primarily driven by commercial and G&A expenses related to the Horizon acquisition. Full year non-GAAP SG&A expenses increased 5% year-over-year, primarily driven by commercial and G&A expenses related to the Horizon acquisition, partially offset by a decline in other marketed product spend. Non-GAAP OI&E were about $635 million in expense in the fourth quarter, a $168 million increase year-over-year, primarily driven by increased interest expense related to the debt issued for the Horizon acquisition. Full year non-GAAP OI&E was favorable $279 million year-over-year, primarily driven by the change in accounting for the BeiGene investment to the fair value mark-to-market method and by gains related to early debt retirement, partially offset by higher net interest expense.

第四季非 GAAP SG&A 費用年增 20%，主要是由於與 Horizo​​n 收購相關的商業和 G&A 費用。全年非 GAAP SG&A 費用年增 5%，主要是由與 Horizo​​​​n 收購相關的商業和 G&A 費用推動，但部分被其他行銷產品支出的下降所抵消。第四季非 GAAP OI&E 費用約為 6.35 億美元，年增 1.68 億美元，主要是由於與 Horizo​​n 收購發行的債務相關的利息費用增加。全年非 GAAP OI&E 年增 2.79 億美元，主要是由於百濟神州投資會計變更為公允價值按市值計算方法以及與提前債務清償相關的收益（部分被較高的債務償還額所抵消）。淨利息支出。

Our non-GAAP tax rate increased 2.5 percentage points year-over-year to 15.9% in the fourth quarter and 2.7 percentage points year-over-year to 16.5% for the full year primarily due to the 2022 Puerto Rico tax law change mentioned previously. The company generated $7.4 billion of free cash flow in 2023 compared with $8.8 billion in 2022. The decrease is driven by the Horizon transaction and integration costs, higher repatriation tax payments and higher capital expenditures. We expect to continue to generate strong cash flows with the addition of Horizon and are on track with our deleveraging plans to return to our efficient capital structure by the end of 2025.

我們的非公認會計準則稅率在第四季度同比增長 2.5 個百分點至 15.9%，全年同比增長 2.7 個百分點至 16.5%，這主要是由於前面提到的 2022 年波多黎各稅法變化。該公司在2023 年產生了74 億美元的自由現金流，而2022 年為88 億美元。這一下降是由Horizo​​​​n 交易和整合成本、更高的匯回稅和更高的資本支出造成的。我們預計，隨著 Horizo​​n 的加入，我們將繼續產生強勁的現金流，並正在按計劃實施去槓桿化計劃，以在 2025 年底前恢復高效的資本結構。

In summary, we continue to execute on our multiple capital allocation priorities. First, we continue to prioritize investments in both internal and external innovation. Our increased spending and non-GAAP R&D of 8% in '23 over '22, coupled with the acquisition of Horizon Therapeutics, continues to broaden and strengthen our balanced portfolio across therapeutic areas. With our strong late-stage innovative pipeline moving forward through development, we expect our non-GAAP R&D to continue to increase in 2024.

總之，我們繼續執行多項資本配置優先事項。首先，我們持續優先投資內部和外部創新。與 22 年相比，23 年我們的支出和非公認會計準則研發增加了 8%，再加上 Horizo​​​​n Therapeutics 的收購，繼續擴大和加強我們在治療領域的平衡投資組合。隨著我們強大的後期創新管道不斷發展，我們預計我們的非 GAAP 研發將在 2024 年繼續增加。

Second, we continue investing in our business for long-term growth, including our state-of-the-art manufacturing facilities in Ohio and North Carolina. Amgen Ohio, our new advanced assembly and final product packaging plant, has just received licensure from the FDA for commercial production in January, roughly 2 years after we broke ground, and our innovative drug substance plant under construction in North Carolina is expected to be operational by 2026. In addition, we've positioned the organization to accelerate investments in innovation, including leveraging the power of generative artificial intelligence. And third, we return capital to shareholders through growing dividends, including $2.13 per share in the quarter. This represented a 10% increase over that paid in each of 2022's 4 quarters.

其次，我們繼續投資我們的業務以實現長期成長，包括我們在俄亥俄州和北卡羅來納州的最先進的製造設施。安進俄亥俄州是我們新的先進組裝和最終產品包裝工廠，在我們破土動工大約兩年後，於1 月份剛剛獲得FDA 的商業生產許可，而我們在北卡羅來納州正在建設的創新原料藥工廠預計將投入營運到 2026 年。此外，我們也讓該組織加速創新投資，包括利用產生人工智慧的力量。第三，我們透過增加股利（包括本季每股 2.13 美元）向股東返還資本。這比 2022 年 4 個季度每季的支付額增加了 10%。

Turning to the outlook for the business for 2024. First, because this is the first full year incorporating the impact of Horizon, we're providing some additional granularity in our guidance, which we don't expect to repeat to the same extent in the future. For 2024, we're expecting revenue of $32.4 billion to $33.8 billion and non-GAAP earnings per share of $18.90 to $20.30. As we continue to integrate Horizon, we expect the acquisition to be accretive to non-GAAP EPS in 2024. And we're on track to meet the synergies target previously communicated of at least $500 million in pretax cost by year 3 after closing or in 2026. Our revenue range reflects our strong growth outlook driven by numerous opportunities across our 4 therapeutic area pillars. We will record a full year of legacy Horizon product sales, and we expect continued volume-driven growth in our priority products, Repatha, TEZSPIRE, EVENITY, Otezla, Prolia and BLINCYTO. Consistent with industry trends in our recent history, we expect mid-single-digit price decline for our portfolio in 2024.

談到2024 年的業務前景。首先，由於這是納入Horizo​​​​n 影響的第一個全年，我們在指導中提供了一些額外的粒度，我們預計不會在2024 年的指導中以相同程度重複這些內容。未來。 2024 年，我們預計營收為 324 億美元至 338 億美元，非 GAAP 每股收益為 18.90 美元至 20.30 美元。隨著我們繼續整合 Horizo​​​​n，我們預計此次收購將在 2024 年增加非 GAAP 每股收益。我們預計在交易結束後的第 3 年或在2026 年。我們的收入範圍反映了我們在4個治療領域支柱的眾多機會的推動下強勁的成長前景。我們將記錄全年傳統 Horizo​​n 產品銷售量，並預計我們的優先產品 Repatha、TEZSPIRE、EVENITY、Otezla、Prolia 和 BLINCYTO 將繼續實現銷售驅動的成長。與我們近期歷史上的行業趨勢一致，我們預計 2024 年我們的投資組合價格將出現中等個位數的下降。

As a reminder, as you model the first quarter of 2024 and consistent with our historical trends, we expect first quarter product sales to be the lowest quarter as a percentage of the full year due to benefit plan changes, insurance reverifications and increased co-pay charges. So we expect the first quarter of 2024 total revenue to grow roughly 20% year-over-year. For the full year, we expect other revenue to be in the range of approximately $1.3 billion to $1.4 billion. And we continue to efficiently run the business through our disciplined approach to managing operating expenses.

提醒一下，當您對2024 年第一季進行建模並與我們的歷史趨勢保持一致時，由於福利計劃變化、保險重新驗證和自付額增加，我們預計第一季產品銷售額佔全年的比例將是最低的季度收費。因此，我們預計 2024 年第一季總營收將年增約 20%。我們預計全年其他收入約為 13 億美元至 14 億美元。我們繼續透過嚴格的管理營運費用的方法來有效地經營業務。

In 2024, we're making incremental R&D investments to support our promising late-stage pipeline, including our rapidly advancing oncology programs as discussed following ESMO in October and other programs, including MariTide. Furthermore, the addition of Horizon has an impact on the 2024 operating margin given the timing of when synergies are realized.

2024 年，我們將進行增量研發投資，以支持我們前景光明的後期研發管線，包括我們在 10 月份 ESMO 會議後討論的快速推進的腫瘤學項目以及 MariTide 等其他項目。此外，考慮到實現協同效應的時間，Horizo​​​​n 的加入會對 2024 年的營運利潤率產生影響。

As a result, we project the full year non-GAAP operating margin as a percentage of product sales to be roughly 48%. Note that we expect non-GAAP operating margin growth to accelerate in each of the quarters following the first quarter.

因此，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 48%。請注意，我們預計非公認會計準則營業利潤率在第一季之後的每季都會加速成長。

There are primarily 3 reasons for this: first, typical lower product sales in Q1, as I mentioned above, and in each of the following quarters; second, increased spend on our commercial brands will continue, building on the investments we made in the second half of 2023, including Repatha, Otezla and our bone portfolio, EVENITY and Prolia; and third, Q1 2024 reflects the addition of Horizon, for which we are just at the beginning stages of realizing synergies given the acquisition close date of October 6.

造成這種情況的原因主要有3個：首先，正如我上面提到的，第一季以及接下來的每個季度的產品銷售通常較低；其次，我們將繼續增加對商業品牌的支出，以我們在 2023 年下半年進行的投資為基礎，包括 Repatha、Otezla 以及我們的骨骼產品組合 EVENITY 和 Prolia；第三，2024 年第一季反映了 Horizo​​n 的加入，考慮到收購截止日期為 10 月 6 日，我們正處於實現協同效應的開始階段。

So we expect non-GAAP operating margin to be roughly 43% in the first quarter. I would reiterate that we expect operating margin growth to accelerate in each of the quarters following the first quarter. We project non-GAAP cost of sales to be in the range of 17% to 18% as a percentage of product sales for the 2024 year. Taking into account the full year of Horizon-related expenses, we expect non-GAAP R&D expenses in 2024 to increase approximately 20% year-over-year, with investments also increasing to advance key pipeline assets, including AMG 193, MariTide, rocatinlimab and tarlatamab. We see significant potential in our innovative pipeline, and it is important that we strategically invest now to fully unlock the opportunities ahead to create long-term value for patients, staff and shareholders.

因此，我們預計第一季非 GAAP 營業利潤率約為 43%。我要重申的是，我們預計第一季之後的每季營業利潤率都會加速成長。我們預計 2024 年非 GAAP 銷售成本佔產品銷售額的比例將介於 17% 至 18% 之間。考慮到全年 Horizo​​​​n 相關費用，我們預計 2024 年非 GAAP 研發費用將年增約 20%，投資也將增加以推進關鍵管道資產，包括 AMG 193、MariTide、rocatinlimab 和塔拉塔馬布。我們看到我們的創新管道具有巨大潛力，因此我們現在進行策略性投資非常重要，以充分釋放未來的機會，為患者、員工和股東創造長期價值。

And for non-GAAP SG&A spend, we expect 2024 full year amounts as a percentage of product sales to be between 21% and 22%. We anticipate non-GAAP OI&E to be in the range of $2.6 billion to $2.7 billion. As mentioned on our Q3 '23 call, the '24 guidance includes the interest expense related to the $28 billion of debt rates for the Horizon acquisition.

對於非 GAAP SG&A 支出，我們預計 2024 年全年金額佔產品銷售額的百分比將在 21% 至 22% 之間。我們預計非 GAAP OI&E 的營收將在 26 億至 27 億美元之間。正如我們在 23 年第三季電話會議中提到的，24 年指引包括與 Horizo​​n 收購的 280 億美元債務利率相關的利息費用。

We expect a non-GAAP tax rate of 16% to 17%. Our guidance is primarily being driven by 2 factors. The first is the jurisdictional mix of income, including the full year benefits associated with the Horizon transaction, and the legal entity rationalization undertaken in the fourth quarter of 2023 in part to integrate the Horizon entities into our existing U.S.-headquartered legal entity structure. The second is the benefit from a planned payment to the IRS as an advanced deposit as we've done in the past to stop the accrual of interest on uncertain tax positions. There is no change in our belief in the merits of our legal arguments with the IRS as we prepare for trial.

我們預計非 GAAP 稅率為 16% 至 17%。我們的指導主要由兩個因素驅動。第一個是司法管轄區的收入組合，包括與Horizo​​​​n 交易相關的全年收益，以及2023 年第四季度進行的法人實體合理化，部分目的是將Horizo​​​​n 實體整合到我們現有的總部位於美國的法人實體結構。第二個是計劃向國稅局支付預付款的好處，就像我們過去所做的那樣，以阻止不確定的稅收狀況產生利息。在我們準備審判的過程中，我們對與國稅局的法律論證的合理性的信念沒有改變。

Given the interest rate environment, although the deposit negatively affects our cash flow in '24, if any of the deposit is returned to us upon the resolution of our litigation, those funds would accrue interest income. Therefore, the rate arbitrage makes this payment a prudent use of our capital. Once again, out of an abundance of clarity, this represents no change in our belief in the merits of the tax court case. The guidance also includes the impact of the adoption of the OECD 15% minimum tax by certain jurisdictions. Based on our individual footprint, we don't anticipate any significant effects of the new rules in 2024, but we're closely watching the global tax landscape for future impacts as the framework continues to be considered by additional jurisdictions and new rules take effect. We expect governments around the world, including the United States, to continue to look for more sources of tax revenue from large multinational corporations that could result in higher taxes in the coming years.

考慮到利率環境，儘管存款對我們24年的現金流產生負面影響，但如果我們的訴訟解決後將任何存款返還給我們，這些資金將產生利息收入。因此，利率套利使這筆款項成為我們資本的謹慎使用。再次明確的是，這並不代表我們對稅務法庭案件的是非曲直的信念沒有改變。該指南還包括某些司法管轄區採用經合組織 15% 最低稅率的影響。根據我們的個人足跡，我們預計新規則在 2024 年不會產生任何重大影響，但隨著其他司法管轄區繼續考慮該框架以及新規則生效，我們正在密切關注全球稅收格局的未來影響。我們預計，包括美國在內的世界各國政府將繼續從大型跨國公司尋找更多稅收來源，這可能會導致未來幾年的稅收增加。

Similar to 2023, we expect share repurchases not to exceed $500 million in 2024. We expect that we will continue to increase our dividend. We expect capital expenditures of approximately $1.1 billion in 2024, consistent with our capital allocation priority to invest in our business, including the Ohio and North Carolina facilities I mentioned ahead and into the rare disease pillar.

與 2023 年類似，我們預計 2024 年股票回購不會超過 5 億美元。我們預計將繼續增加股利。我們預計 2024 年的資本支出約為 11 億美元，這與我們投資於我們業務的資本分配優先順序一致，包括我前面提到的俄亥俄州和北卡羅來納州的設施以及罕見疾病支柱。

In summary, we delivered another strong year of financial results in 2023. Our confidence in the long-term growth of Amgen is strong, and we believe that our new rare disease pillar, 1 of our 4 pillars, will be an important additive source of growth for the company. This concludes the financial update. My thanks to my approximately 27,000-plus colleagues at Amgen around the world for their commitment to our mission of serving patients and their tireless efforts in 2023.

總而言之，我們在 2023 年再次取得了強勁的財務業績。我們對安進的長期成長充滿信心，我們相信，我們新的罕見疾病支柱（我們的四大支柱之一）將成為重要的附加來源為公司的成長。財務更新到此結束。我感謝世界各地約 27,000 多名安進同事對我們為病人服務的使命的承諾以及他們在 2023 年的不懈努力。

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

我會將其轉回給鮑勃進行問答。

Okay. Thank you. Let's open the line, and we'll take questions from our callers. And Julianne, why don't you remind them of the procedures, so we can get through these questions here efficiently for everyone.

好的。謝謝。讓我們打開電話，我們將回答來電者的問題。 Julianne，為什麼不提醒他們這些程序，這樣我們就可以在這裡有效地為每個人解決這些問題。

(Operator Instructions) Our first question comes from Michael Yee from Jefferies.

（操作員說明）我們的第一個問題來自 Jefferies 的 Michael Yee。

Thanks for good results and good guidance. We had a question on obesity. On 133, of course, you had the publication yesterday. I feel like it was the most scrutinized Phase I publication. But maybe you could just talk to -- maybe Jay could talk to your interpretation of some of the markers, for example, lipids, A1c, blood pressure and all that kind of thing. And maybe talk about your confidence level about the profile versus competitors.

感謝良好的結果和良好的指導。我們有一個關於肥胖的問題。當然，您昨天在 133 上收到了該出版物。我覺得這是最受關注的第一階段出版品。但也許你可以談談——也許傑伊可以談談你對某些標誌物的解釋，例如血脂、糖化血紅蛋白、血壓和所有類似的東西。也許還可以談談您相對於競爭對手對個人資料的信心程度。

Yes. Thanks a lot, Michael. We really appreciate the consideration the Phase I paper is receiving from the community. It's exciting to report these data. For those who haven't seen it, this was a randomized, double-blind, placebo-controlled study, 49 patients looking at safety, PK, PD, single ascending dose, 7 cohorts, multiple ascending dose 3 cohorts, 3 monthly doses, patients with obesity, BMI greater than 30. And we were quite pleased with the outcome. Looking at the 420-milligram dose, as an example, which was the highest dose study, 14.5% weight loss at only day 85. And moreover, quite durable coming off of that medicine out to 150 days, all with relatively mild gastrointestinal side effects. And so to answer your last question first, we find the Phase I data, which we're pleased to share with the community, to be quite supportive of our ongoing work to develop this medicine to the greatest possible benefit of patients suffering from obesity.

是的。非常感謝，麥可。我們非常感謝社區對第一階段論文的關注。報告這些數據令人興奮。對於那些還沒有看過它的人來說，這是一項隨機、雙盲、安慰劑對照研究，49 名患者關注安全性、PK、PD、單次遞增劑量、7 個隊列、多次遞增劑量3 個隊列、3 個月劑量、 BMI大於30的肥胖患者。我們對結果非常滿意。以 420 毫克劑量為例，這是最高劑量的研究，僅第 85 天體重就減輕了 14.5%。而且，該藥物的藥效相當持久，長達 150 天，且胃腸道副作用相對較輕。因此，首先回答你的最後一個問題，我們發現第一階段的數據非常支持我們正在進行的開發這種藥物的工作，我們很高興與社區分享這些數據，以便為肥胖患者帶來最大的利益。

Now you've asked questions around some of the measurements on the study, lipid, blood pressure and A1c. And I would just caution that this is a Phase I trial, the numbers are very small, that the duration of treatment is rather short. But even with all of those caveats, while hard to draw conclusions from such small numbers, especially labile measurements like blood pressure and lipids, all are directionally favorable. And so we have -- we take no concern whatsoever from those measurements on the study.

現在您已經就研究中的一些測量值、血脂、血壓和 A1c 提出了問題。我想提醒一下，這是第一階段試驗，人數非常少，治療時間也相當短。但即使有所有這些警告，雖然很難從如此小的數字中得出結論，特別是血壓和血脂等不穩定的測量結果，但所有這些都是有方向性的。因此，我們對這項研究的測量結果不存在任何擔憂。

Our next question comes from Salveen Richter from Goldman Sachs.

我們的下一個問題來自高盛的 Salveen Richter。

Another one here on the obesity program. So post the published Phase I data, how are you thinking about differentiation on GI tolerability? Is the dose range being evaluated in the Phase II study similar to that in the Phase I?

另一篇關於肥胖計劃的文章。因此，發布已發布的第一階段數據後，您如何考慮胃腸道耐受性的差異化？ II 期研究中評估的劑量範圍是否與 I 期研究的相似？

Yes. Thanks for the question. I'll take this one as well. As you may or may not know, the Phase II study, which is ongoing at present and going very well, explores 11 dosing cohorts with relevant placebo controls. And through that study, we'll have a chance to gain an experience with a longer exposure to MariTide dosed in different ways. We've recently added a part 2 to this study that will allow us to explore even more durable weight loss beyond 52 weeks enabled by just very rapid enrollment. And these 4 dosing cohorts will go on to test dose level and even less frequent dosing schedules than monthly. And so these Phase II data, even by end of year, will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into Phase III clinical investigation.

是的。謝謝你的提問。我也拿這個吧。您可能知道也可能不知道，目前正在進行且進展順利的 II 期研究探索了 11 個劑量組和相關安慰劑對照。透過這項研究，我們將有機會獲得以不同方式長期接觸 MariTide 的經驗。我們最近在這項研究中添加了第二部分，這將使我們能夠探索透過快速入組實現 52 週以上更持久的減肥效果。這 4 個給藥組將繼續測試劑量水平，甚至比每月頻率更低的給藥方案。因此，即使到今年年底，這些 II 期數據也將對尋找安全、耐受和有效的劑量進行 III 期臨床研究具有很強的指導意義。

Yes. The only thing I would add is we're starting from a basis of a monthly dosing cadence and schedule. And so the additional dosing cohorts would look at potential dosing schedule beyond monthly. And the data are pretty clear in the market right now. The GI toxicity or GI side effects are generally related to the day of dosing of the GLP-1s, which are dosed weekly. We see some of that same GI side effect profile in kind of the first dose part of the dose titration. But there's an opportunity here to potentially spread the dosing intervals out further and further improve tolerability in our program. And as Jay clearly described, we've got all of the different aspects of that being studied in the Phase II program.

是的。我唯一要補充的是，我們是從每月的給藥節奏和時間表開始的。因此，額外的給藥組將考慮每月以外的潛在給藥方案。目前市場上的數據已經非常清楚了。胃腸道毒性或胃腸道副作用通常與 GLP-1 的給藥日期有關，每週給藥一次。我們在劑量滴定的第一劑量部分看到了一些相同的胃腸道副作用。但這裡有機會進一步延長給藥間隔並進一步提高我們計劃的耐受性。正如 Jay 明確描述的那樣，我們已經在第二階段專案中研究了所有不同的方面。

Our next question comes from Jay Olson from Oppenheimer.

我們的下一個問題來自奧本海默的傑伊·奧爾森。

Congrats on the progress. Another question on 133. Talk about whether or not (inaudible) that we see later this year will include patients from (inaudible) of the study? And do you think it's possible that 133 could be dosed once every 2 or 3 months? And also, if you could just comment on the rollover rate of patients from part 1 to part 2?

祝賀取得的進展。關於 133 的另一個問題。談談我們今年稍後看到的（聽不清楚）是否將包括來自該研究（聽不清楚）的患者？您認為 133 有可能每 2 或 3 個月注射一次嗎？另外，您能否評論一下患者從第 1 部分到第 2 部分的滾動率？

Jay, could you catch all that? Some of what Jay asked was broken up there at the beginning.

傑伊，你能聽清楚這一切嗎？傑伊問的一些問題一開始就被分解了。

The third part was a little bit broken off of your question. I heard a better explanation of part 2 frequency of dosing. And then I did not hear your third part.

第三部分有點脫離了你的問題。我聽到了關於第 2 部分給藥頻率的更好解釋。然後我就沒有聽到你的第三部分了。

If you'd just comment on the rate of patients rolling over from part 1 to part 2.

如果您只想評論一下患者從第 1 部分轉到第 2 部分的比率。

Okay. Yes. Thank you for the question, Jay. Let me give a little bit of context on this part 2 study that I think will help answer them. In part 2, the intent is to really look at durable weight loss beyond 52 weeks. And so by durable weight loss, patients eligible for part 2, which begins at the end of 52 weeks, will be responding to this medicine. And then they'll be rerandomized to 4 cohorts. That will test dose level and, again, this even less frequent dosing schedule. We have not disclosed the granularity on the dosing schedule. This is a competitive environment. But we're afforded this chance because the ADC, the antibody core of MariTide, like so many immunoglobulin therapeutics, allows for the opportunity to use it much less frequently. The rate of patients rolling over to part 2 will be established as the Phase II study continues to progress this year.

好的。是的。謝謝你的提問，傑伊。讓我提供一些有關第二部分研究的背景信息，我認為這將有助於回答這些問題。第 2 部分的目的是真正研究 52 週後的持久減肥效果。因此，透過持久的減肥，符合第 2 部分（從 52 週結束時開始）的患者將對這種藥物產生反應。然後他們將被重新隨機分成 4 組。這將測試劑量水平，並且再次測試頻率較低的給藥方案。我們尚未透露給藥方案的粒度。這是一個競爭的環境。但我們之所以有這個機會，是因為 ADC（MariTide 的抗體核心）與許多免疫球蛋白療法一樣，允許有機會減少使用它的頻率。隨著今年第二階段研究的繼續進展，將確定轉到第二部分的患者比例。

Our next question comes from Chris Schott from JPMorgan.

我們的下一個問題來自摩根大通的克里斯·肖特。

Just maybe to pivot over to TEPEZZA for a question. Can you just talk a little bit about the dynamics for 2024? It seems like the products come back to growth. But I'm just trying to get a sense of now that Amgen owns the asset and has more kind of time with it, what are your top priorities? And how do you think about continuing to kind of grow the new patient base here?

也許只是轉向 TEPEZZA 詢問一個問題。能簡單談談 2024 年的動態嗎？產品似乎又恢復成長了。但我只是想了解安進現在擁有該資產並且有更多的時間來使用它，您的首要任務是什麼？您如何看待繼續擴大這裡的新患者群？

Sure. Chris, maybe we'll take it in a couple of parts. But Vikram, share your thoughts first.

當然。克里斯，也許我們會分成幾個部分來討論。但是維克拉姆，請先分享你的想法。

Yes. Thank you for the question. I think if you focus a little bit on what are the underlying factors that are driving TEPEZZA growth, we saw a record number of unique TEPEZZA prescribers. We saw an increase in patient enrollment forms and patient starts. In addition, we've made pretty significant progress on payer coverage as we've seen our covered lives have now increased to greater than 50% of U.S. covered lives, and that's important. Educating some of those stakeholders on the new clinical data, updated indication, it continues to drive uptake across the full spectrum of TED patients. And finally, what holds all of this together is a really robust patient service model that supports patient access.

是的。感謝你的提問。我認為，如果您稍微關註一下推動 TEPEZZA 成長的潛在因素，我們會發現獨特 TEPEZZA 處方者的數量創歷史新高。我們看到患者登記表和患者開始數量增加。此外，我們在付款人承保範圍方面取得了相當大的進展，我們的承保壽命現已增加到美國承保壽命的 50% 以上，這一點很重要。透過對一些利害關係人進行新的臨床數據和更新的適應症的教育，它繼續推動所有 TED 患者的接受。最後，將所有這些結合在一起的是一個真正強大的患者服務模型，可支援患者訪問。

I think we continue to make progress and execute towards each one of these important leading indicators. And we shouldn't forget that there is still low penetration of the approximately 100,000 patients that can be eligible for this medicine in the U.S. alone.

我認為我們將繼續取得進展並執行這些重要的領先指標中的每一項。我們不應該忘記，僅在美國，大約 10 萬名有資格使用這種藥物的患者的普及率仍然很低。

Now just one last point here is that as we've noted before, there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers. As we said before, it can take up to 90 days once a patient is identified for therapy for that patient to actually get on therapy. But we're pretty happy with all of our leading indicators and the execution that we have seen coming out of last year.

最後一點是，正如我們之前指出的，所有這些努力的執行和患者數量增加之間仍然存在時間延遲。正如我們之前所說，一旦確定患者需要接受治療，該患者可能需要長達 90 天的時間才能真正接受治療。但我們對去年的所有領先指標和執行情況感到非常滿意。

And Chris, the only thing I would add is, building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well. And I think he characterized that well previously. And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of TED patients. So all in all, I feel excited about the rare disease pillar that we've established and the role that TEPEZZA will play in it.

克里斯，我唯一要補充的是，基於維克拉姆在他準備好的演講中所說的話，我們也對國際機會感到興奮。我認為他之前就已經描述過這一點。我們也對我們認為持續投資創新以造福 TED 患者的機會感到興奮。總而言之，我對我們建立的罕見疾病支柱以及 TEPEZZA 將在其中發揮的作用感到興奮。

Our next question comes from Evan Seigerman from BMO Capital Markets.

我們的下一個問題來自 BMO 資本市場的 Evan Seigerman。

I wanted to touch on TEZSPIRE specifically in COPD. How are you planning to differentiate given the pretty competitive data we saw from Dupixent? And how should investors be looking at this data from an efficacy bar? Are there nuances in this trial that need to be clarified that might make it harder to do an apples-to-apples comparison?

我想談談 TEZSPIRE 特別是在慢性阻塞性肺病方面的情況。鑑於我們從 Dupixent 看到的極具競爭力的數據，您打算如何實現差異化？投資人該如何看待功效欄上的這些數據？這項試驗中是否存在需要澄清的細微差別，從而可能使進行同類比較變得更加困難？

Yes. Evan, thanks for the question. Murdo, why don't I start and then you add on. So it's a great and timely question. The Phase II COPD study of TEZSPIRE, we expect data in the first half of this year. This was a big study, 337 patients, moderate to severe COPD. They're having exacerbations despite being on triple therapy, and so reflective of the current unmet need and inadequacy of therapy for patients with COPD.

是的。埃文，謝謝你的提問。默多，為什麼我不先開始，然後你再補充。所以這是一個偉大而及時的問題。 TEZSPIRE的COPD II期研究，我們預計今年上半年有數據。這是一項大型研究，涉及 337 名中度至重度慢性阻塞性肺病患者。儘管接受三聯療法，但他們的病情仍在惡化，這反映了當前慢性阻塞性肺病患者的需求未被滿足和治療不足。

This is a slightly broader population than Dupi that we're studying here. We're totally on track for the readout. We quite like the mechanism here. You must know that TSLP works as a signaling factor upstream. And by blocking it with our unique biotherapeutic, we block TSLP, IL-25, IL-33 signaling. TSLP hits so many cell types, modulating this airway type 2 response. By hitting TSLP upstream, we think we can really have an impact on the disease biology.

這是一個比我們在這裡研究的杜皮人稍微廣泛的人群。我們完全步入讀數的正軌。我們非常喜歡這裡的機制。您必須知道 TSLP 是上游的訊號因素。透過使用我們獨特的生物治療藥物來阻斷它，我們阻斷了 TSLP、IL-25、IL-33 訊號傳導。 TSLP 攻擊多種細胞類型，調節這種氣道 2 型反應。透過攻擊 TSLP 上游，我們認為我們確實可以對疾病生物學產生影響。

We see TSLP elevated in the serum of patients in bronchial mucosa and bronchoalveolar lavage fluid. It's released by airway epithelium. There's just a lot of signals from the basic biology of this disease pointing to a medicine of this nature. And by looking at the broader population than they did with Dupi, we have a chance to really figure out who the responder is. Murdo?

我們發現患者支氣管黏膜和支氣管肺泡灌洗液中的血清 TSLP 升高。它由氣道上皮釋放。這種疾病的基礎生物學中有很多訊號都指向這種性質的藥物。透過觀察比 Dupi 更廣泛的人群，我們有機會真正找出回應者是誰。默多？

I think you've covered all the bases. I would just add this, Evan, that with the unique and differentiated mechanism, as Jay described, we hope we can treat a broader population of patients than perhaps the currently available therapies. And we also recognize that there are patients who are refractory to those currently available therapies, and we would obviously want to understand if they would be responders to TEZSPIRE. I think we've got strong commercial capabilities, including with our partners at AstraZeneca, and are well positioned to take a product like this into the market if we're successful in Phase III.

我想你已經涵蓋了所有的基礎。我想補充一點，埃文，正如傑伊所描述的那樣，透過獨特且差異化的機制，我們希望能夠比目前可用的療法治療更廣泛的患者群體。我們也意識到，有些患者對目前可用的療法有抵抗力，我們顯然想了解他們是否會對 TEZSPIRE 有反應。我認為我們擁有強大的商業能力，包括與阿斯特捷利康的合作夥伴的合作，如果我們在第三階段取得成功，我們就可以將這樣的產品推向市場。

Our next question comes from Umer Raffat from Evercore ISI.

我們的下一個問題來自 Evercore ISI 的 Umer Raffat。

I wanted to touch up on AMG 133 as well, 2 parts question. First, on the discontinuations at the high dose, we know 5 out of 8 did not finish the full duration of the study. But there was a second arm also of this high-dose 420-milligram with 10 patients, which was not reported. This was the one with digital tools. Could you speak to the discontinuation rate in that arm? This is the 420 done separately, which is not part of the paper.

我也想談談 AMG 133，這是兩個部分的問題。首先，關於高劑量的停藥，我們知道八分之五的人沒有完成整個研究期間。但第二組也接受了 10 名患者的 420 毫克高劑量治療，但未有報告。這是有數位工具的。能談談該手臂的停藥率嗎？這是單獨做的420，不屬於論文的一部分。

And secondly, I know there's a case of liver enzyme elevation of the 280 mg dose, but this patient also had COVID. Could you perhaps speak to the timing of liver enzyme elevation relative to the COVID episode?

其次，我知道有一例服用 280 毫克劑量後肝酵素升高的病例，但該患者也患有新冠病毒。能否談談肝酵素升高相對於新冠肺炎發作的時間？

Yes. Thanks, Umer. I won't be able to provide patient level insights to the Phase I study at this time, but I do appreciate your question and your interest in the report. I'll speak to the dropouts of the Phase I at the 420-milligram dose, which was 4 out of the 8 patients. First, it's notable to say that the high dose cohort in the multiple ascending dose receiving the 3 doses of 420 experienced real weight loss, real benefit of 14.5% after these 3 monthly doses. This was the group that proved actually quite durable out to day 150. Four subjects declined to participate in this clinical study setting largely for logistical reasons. The AEs and other characteristics were comparable to all the other patients in the study. Now the second question around the digital group, I don't have insight into that. Dave, do you?

是的。謝謝，烏默。我目前無法提供第一階段研究的患者層面的見解，但我非常感謝您的提問以及您對報告的興趣。我將談談 420 毫克劑量的 I 期試驗中退出的情況，這是 8 名患者中的 4 名。首先，值得注意的是，接受 3 劑 420 的多次遞增劑量中的高劑量組經歷了真正的體重減輕，在這 3 個月的劑量後，實際獲益為 14.5%。事實證明，這一組實際上相當能堅持到第 150 天。四名受試者拒絕參與這項臨床研究，主要是出於後勤方面的原因。 AE 和其他特徵與研究中的所有其他患者相當。現在是關於數位組的第二個問題，我對此沒有深入的了解。戴夫，你呢？

No. I mean we can get back to you on that. I don't know that we reported that -- those data in the discontinuation rate.

不，我的意思是我們可以就此回覆您。我不知道我們是否報道過那些關於停藥率的數據。

Our next question comes from Colin Bristow from UBS.

我們的下一個問題來自瑞銀集團的柯林布里斯托。

Maybe a couple more on MariTide. First, could you provide some insight into the dosing? I mean, obviously, these are pretty large doses. And if we look at -- like Repatha 420 milligrams takes over 5 minutes by infusion or 3 consecutive injections. So I was wondering if you could give any insight there.

也許 MariTide 上還有更多。首先，您能提供一些有關劑量的見解嗎？我的意思是，顯然，這些劑量相當大。如果我們看一下，像 Repatha 420 毫克輸注或連續 3 次注射需要 5 分鐘以上。所以我想知道你是否可以提供任何見解。

And then in terms of the relative affinity for GIPs versus GLPs, MariTide seems to have -- or preferentially favor GLP much more than competitor molecules. And so do you think the ultimate clinical profile is more closely going to resemble that of the long-acting GLP-1 versus competitor GLPs?

然後，就 GIP 與 GLP 的相對親和力而言，MariTide 似乎比競爭對手分子更青睞 GLP。那麼您是否認為最終的臨床特徵與長效 GLP-1 相比競爭對手的 GLP 更相似？

Yes. Thanks, Colin. I appreciate the deep consideration of the molecule, especially. I'd start by saying I don't regard these doses as high. I'm new here. But 420 milligrams for a biotherapeutic that's an antibody drug conjugate with a peptide antibody ratio of 2:1 seems well in scope for a modern biotherapeutic product. I don't need to tell this community paying so close -- such close attention to Amgen that this is a very sophisticated biotherapeutics organization and on the manufacturing side, just every patient every time, and that we have all the capabilities necessary to deliver this medicine at whichever of these 3 or other dose and schedule we arrive at. So no concerns there for me whatsoever.

是的。謝謝，科林。我特別欣賞對分子的深入思考。我首先要說的是，我不認為這些劑量很高。我是新來的。但 420 毫克的生物治療藥物是一種勝肽抗體比例為 2:1 的抗體藥物綴合物，似乎完全符合現代生物治療產品的範圍。我不需要告訴這個對安進如此密切關注的社區，這是一個非常複雜的生物治療組織，在製造方面，每次都是每一位患者，我們擁有實現這一目標所需的所有能力我們採用這3 種或其他劑量和時間表中的任何一種進行治療。所以我根本不用擔心。

Regarding the balance of the pharmacology, you do invoke a difference between our medicine and medicines developed by peer pharmaceutical companies, namely mechanistically, the core antibody of MariTide inhibits the GIP receptor, whereas these other peptide medicines agonize it. We feel very secure in our choice to inhibit that receptor supported by just the finest level of experimental data available, experiments of nature that genome-wide association studies in very large populations have pointed to a need, an opportunity to inhibit the GIP receptor to deliver lower BMI as observed with variance in that receptor and downstream signaling pathways that correlate with reduced body mass index in large populations.

關於藥理學的平衡，您確實提到了我們的藥物與同行製藥公司開發的藥物之間的差異，即從機制上講，MariTide的核心抗體是抑制GIP受體的，而其他肽類藥物是激動它的。我們對抑制該受體的選擇感到非常安全，這一選擇得到了現有最好水平的實驗數據的支持，在非常大的人群中進行的全基因組關聯研究表明，自然實驗需要一個抑制GIP 受體的機會，以實現這一目標。觀察到的 BMI 較低，受體和下游信號通路存在差異，而這些差異與大量人群的體重指數降低有關。

As to the balance, which you ask, between inhibition of GIP receptor and agonism of GLP-1, these are very difficult measurements to make in humans. But our modeling suggests that, with the therapeutic doses and exposures that we observe, that we are achieving both.

至於你問的 GIP 受體抑制和 GLP-1 激動之間的平衡，這些在人類很難測量。但我們的模型表明，根據我們觀察到的治療劑量和暴露量，我們正在實現這兩點。

And Colin, it's Murdo. I would just add that from a patient experience perspective, we've learned a lot from other biologics. And Amgen has a world-class process development, manufacturing and device team, and we've done a lot of work on this one and we anticipate a very positive and simple patient experience on at least a monthly dosing schedule. And we've learned a lot from Repatha specifically, and there's more to follow on Repatha from that, but we continue to work to improve patient experience with our biologic injectables.

科林，是默多。我想補充一點，從患者體驗的角度來看，我們從其他生物製劑中學到了很多。安進擁有世界一流的製程開發、製造和設備團隊，我們在這方面做了很多工作，我們預計至少在每月的給藥計劃中會帶來非常積極和簡單的患者體驗。我們從 Repatha 身上學到了很多東西，而且 Repatha 可以從中學到更多東西，但我們將繼續努力改善患者對我們的生物注射劑的體驗。

Just as we go to the next question, let me observe that we're almost up to the hour that we actually all set aside because I know we still have quite a few questions in the queue. So we'll try to get one question per caller here and get through. We'll stay through the queue of calls or questions rather that's still waiting for us, but I know some of you may have to drop.

就在我們討論下一個問題時，讓我觀察一下，我們幾乎已經到了我們實際上都預留的時間了，因為我知道我們還有很多問題在排隊。因此，我們將嘗試向每個來電者詢問一個問題並接通。我們將留在電話或問題隊列中，而不是仍在等待我們，但我知道你們中的一些人可能不得不放棄。

Our next question comes from Yaron Werber from TD Cowen.

我們的下一個問題來自 TD Cowen 的 Yaron Werber。

All right. Great. This is Brendan on for Yaron. Just a quick one from us, actually. Based on the data you've seen so far and maybe some feedback from physicians that you've heard, this is on UPLIZNA. Where do you kind of see UPLIZNA fitting into maybe the MG treatment paradigm given all the competition there, but maybe more to the point, how you're thinking about expansion opportunities, given all the different autoimmune indications you could potentially pursue? Just trying to kind of understand how you see longer-term growth there.

好的。偉大的。這是布倫丹 (Brendan) 替補亞龍 (Yaron)。實際上，我們只是簡單介紹一下。根據您迄今為止看到的數據以及您聽到的醫生的一些反饋，這是在 UPLIZNA 上進行的。考慮到那裡的所有競爭，您認為 UPLIZNA 在哪裡可能適合 MG 治療範式，但也許更重要的是，考慮到您可能追求的所有不同的自身免疫適應症，您如何考慮擴張機會？只是想了解您如何看待那裡的長期成長。

First, why don't we ask Vikram just to address the performance of the product right now in NMOSD, and then a combination of Jay and Dave can talk about the other activities or other potential applications.

首先，我們為什麼不要求 Vikram 解決目前 NMOSD 中產品的效能問題，然後 Jay 和 Dave 可以討論其他活動或其他潛在應用。

Yes. Thanks for the question. Yes, UPLIZNA is actually growing quite nicely and quite fun in NMOSD. As you know, it is now the fastest-growing biologic in NMOSD. We continue to execute across a variety of fronts. I mean we're -- we see this product nicely positioned versus -- as it's appropriate for NMOSD patients and within the competitive environment that we operate in. And we've continued to make significant progress over the last 18 months or so, maybe even longer, of continuing to drive more growth with newer prescribers and even depth with existing prescribers. So the product continues to do well. And I think we hope to continue to deliver good execution on this medicine in NMOSD. Maybe, Jay, you want to talk about the second question?

是的。謝謝你的提問。是的，UPLIZNA 實際上在 NMOSD 中發展得非常好且非常有趣。如您所知，它現在是 NMOSD 中成長最快的生物製劑。我們繼續在各個領域開展工作。我的意思是，我們認為這款產品的定位很好，因為它適合 NMOSD 患者，並且適合我們營運的競爭環境。在過去 18 個月左右的時間裡，我們可能會繼續取得重大進展甚至更長時間，繼續推動新處方者的成長，甚至現有處方者的深度。因此該產品繼續表現良好。我認為我們希望繼續在 NMOSD 中對該藥物進行良好的執行。 Jay，也許你想談談第二個問題？

Yes. No, I'm happy to. As you may know, I'm a hematologist. I think CD19 is a terrific target. It's expressed really on all B-cells and spares plasma cells. And therefore, considering indication expansion, as you've asked, there's a large number of diseases that could potentially be approached with UPLIZNA to the real benefit of patients with unmet need far beyond the application of the prevailing CD20s that target just a subset of B-cells. This is not lost on our team, and we're working through indication expansion priorities presently.

是的。不，我很樂意。如您所知，我是血液學家。我認為 CD19 是一個很棒的目標。它確實在所有 B 細胞上表達，但漿細胞除外。因此，考慮到適應症的擴展，正如您所問的，有大量的疾病可以透過UPLIZNA 來治療，為未滿足需求的患者帶來真正的好處，遠遠超出了僅針對B 子集的流行CD20 的應用-細胞。我們的團隊並沒有忽略這一點，目前我們正在研究適應症擴展的優先事項。

Our next question comes from Mohit Bansal from Wells Fargo.

我們的下一個問題來自富國銀行的 Mohit Bansal。

I have a question regarding the subcutaneous delivery of TEPEZZA. You do have plan to initiate a Phase III study. Can you talk a little bit about, I mean, which technology you are using? Is this with the preexisting Halozyme technology? Or are you using something else for this development?

我對 TEPEZZA 皮下給藥有疑問。您確實計劃啟動 III 期研究。我的意思是，您能談談您正在使用哪種技術嗎？這是現有的 Halozyme 技術嗎？或者您正在使用其他東西來進行此開發？

Sorry, I had trouble understanding the question.

抱歉，我無法理解這個問題。

The question is what technology we're using for the subcutaneous injectable form of TEPEZZA.

問題是我們使用什麼技術來生產 TEPEZZA 的皮下注射形式。

Maybe I'll just jump in. Mohit, we're not commenting at this point on the provider. We just said that we're going forward with the subcu.

也許我會插話。Mohit，我們目前不對提供者發表評論。我們剛剛說過我們將繼續開發 subcu。

Our next question comes from Geoff Meacham from Bank of America.

我們的下一個問題來自美國銀行的傑夫·米查姆。

Another one on 133. When you think about the Phase III program, I just wanted to know what sort of informs the next indications you're going to go after? Is it unmet need? Is it the potential for differentiation on 133? And the timing of that, do you think that you'd want to have the Phase II data in hand? Or is this something that you could roll out sort at risk?

另一篇關於 133 的文章。當你考慮第三階段計劃時，我只是想知道你要追求的下一個跡像是什麼樣的？是未滿足的需求嗎？是133上的差異化潛力嗎？至於時間安排，您認為您願意掌握第二階段的資料嗎？或者這是你可以冒險推出的東西嗎？

Yes. Thanks for the question, Geoff. Really appreciate it. As you know, obesity is a major public health crisis, maybe 40% of Americans with a BMI over 30, massively costly, so huge burden to the global third-party payers and societies. The obesity-related disease list is quite long and expanding from cardiovascular disease and heart failure, type 2 diabetes, obstructive sleep apnea, NASH, NAFLD, kidney disease. These are chronic conditions that really demand medicines that can deliver durable and chronic weight loss. And so we think we have a really strong offering for these obesity-related diseases rising in our Phase II program, as you know. And obesity has a strong genetic component. And we locked on to the GIPR inhibition based on genetic insights. So the opportunity space is quite large. You asked the question what indications and perhaps even in what sequence. And when we have all the requisite data, we'll remark in due course. But we intend all indications where this dual mechanism can improve public health. And we are actively planning and on track for an expansive Phase III program.

是的。謝謝你的提問，傑夫。真的很感激。如你所知，肥胖是一個重大的公共衛生危機，也許40%的美國人的BMI超過30，成本龐大，對全球第三方付款者和社會帶來巨大的負擔。與肥胖相關的疾病清單相當長，包括心血管疾病和心臟衰竭、第2型糖尿病、阻塞性睡眠呼吸中止症、NASH、NAFLD、腎臟疾病。這些都是慢性疾病，確實需要能夠達到持久、慢性減肥的藥物。因此，正如您所知，我們認為我們為第二階段計劃中出現的這些與肥胖相關的疾病提供了非常強大的產品。肥胖有很強的遺傳因素。我們根據遺傳見解鎖定了 GIPR 抑制。所以機會空間還蠻大的。你問的問題是什麼跡象，甚至可能是按什麼順序。當我們掌握所有必要的數據後，我們會在適當的時候發表評論。但我們希望所有跡象表明這種雙重機制可以改善公共衛生。我們正積極規劃並步入擴展的第三階段計畫。

And in terms of -- Dave, do you want to add the regulatory piece?

戴夫，你想加入監管部分嗎？

Yes. I think -- Geoff, this is Dave Reese. I would just add that we're planning a very expansive Phase III program. So you can expect to see multiple indications move forward in parallel. And as Jay indicated, as we start to see data, we will begin launching those trials, and we'll discuss them. And then in addition, as you're aware, regulatory authorities around the world require a certain body of safety data before Phase III launches. And so of course, we will be compliant with that. But our goal is to launch Phase III as quickly as possible once we have the requisite data set and regulatory approval.

是的。我想——傑夫，這是戴夫·里斯。我想補充一點，我們正在計劃一個非常廣泛的第三階段計劃。因此，您可以預期會看到多種跡象並行發展。正如傑伊所指出的，當我們開始看到數據時，我們將開始啟動這些試驗，我們將討論它們。此外，如您所知，世界各地的監管機構在第三階段啟動之前需要一定的安全資料。當然，我們會遵守這一點。但我們的目標是一旦獲得必要的資料集和監管部門的批准，就盡快啟動第三階段。

Our next question comes from David Risinger from Leerink Partners.

我們的下一個問題來自 Leerink Partners 的 David Risinger。

So I have another question on AMG 133, please. Could you add some more color on your expectations for the impacts on blood pressure and lipids in Phase II, specifically whether you anticipate tirzepatide-like efficacy on those metrics?

我還有一個關於 AMG 133 的問題。您能否對第二階段對血壓和血脂的影響的預期添加一些更多的色彩，特別是您是否預期替澤帕肽對這些指標有類似的功效？

Yes. Thanks, David. I mean we're making all these measurements, and I'm not going to try to forecast the outcome of that pharmacology at this time. As you've seen in our Phase I program, the medicine is very well tolerated, delivering durable weight loss and benefit without significant excursion of some of those measurements. I just think it's too early to try to answer your question, and we'll have all that data at the end of the first part of Phase II towards the end of this calendar year.

是的。謝謝，大衛。我的意思是，我們正在進行所有這些測量，而且我目前不會嘗試預測該藥理學的結果。正如您在我們的第一階段計劃中所看到的，該藥物具有良好的耐受性，可實現持久的減肥效果，並且不會使某些測量值出現顯著偏差。我只是認為現在嘗試回答你的問題還為時過早，我們將在今年年底第二階段第一部分結束時獲得所有數據。

And the best extrapolation that you can have is from the preclinical data that were just published. I urge you to take a look at that.

您可以從剛發布的臨床前數據中得到最好的推論。我強烈建議你看看這個。

Our next question comes from Michael Schmidt from Guggenheim Securities.

我們的下一個問題來自古根漢證券公司的邁克爾·施密特。

It's Yige on for Michael. A quick one on xaluritamig. Can you talk about your plan of data disclosure this year and your current thinking on the potential registration path? How do you think about the positioning of this agent relative to some of the other emerging agents based on different mechanisms such as ADC or AR degraders in prostate cancer?

由易格替補邁克爾。關於 xaluritamig 的快速介紹。您能談談您今年的數據揭露計劃以及您目前對潛在註冊路徑的思考嗎？您如何看待該藥物相對於其他一些基於不同機制（例如前列腺癌中的 ADC 或 AR 降解劑）的新興藥物的定位？

Yes. Thanks for this outstanding question, Michael. And xaluritamig is a very interesting and exciting molecule. For those on the call, this is a STEAP1 CD3 bispecific. We have been studying this in advanced castrate-resistant prostate cancer. We have expanded a cohort, the Phase I monotherapy. We're opening to reduced monitoring as well as, as you invoke, the existing and novel androgen receptor modulators integrators. We're exploring combinations with novel agents in that domain as well.

是的。感謝邁克爾提出這個突出的問題。 xaluritamig 是一種非常有趣且令人興奮的分子。對於接聽電話的人來說，這是一種 STEAP1 CD3 雙特異性抗體。我們一直在晚期去勢抵抗性前列腺癌中研究這一點。我們擴大了一個隊列，即 I 期單一療法。我們正在開放減少監測，以及您調用的現有和新型雄激素受體調節劑積分器。我們也在探索與該領域的新型藥物的組合。

The priorities for the program right now are to establish reduced monitoring. This will be important to reach just all the patients who can benefit. We're looking at the feasibility of reduced monitoring. We have great experience with these T-cell engaging bispecifics as well as the possibility of outpatient therapy.

該計劃目前的首要任務是減少監測。這對於惠及所有可以受益的患者來說非常重要。我們正在研究減少監測的可行性。我們在這些 T 細胞參與雙特異性藥物以及門診治療的可能性方面擁有豐富的經驗。

The approach to the regulatory path will present in due course. There will be no surprises there. The path to bring medicines to patients with castrate-resistant prostate cancer alone and ultimately, in combination is well worn, thankfully, and we know how to deliver there.

監管路徑的方法將在適當的時候提出。那裡不會有任何驚喜。值得慶幸的是，為去勢抵抗性前列腺癌患者單獨提供藥物以及最終聯合提供藥物的道路已經過時，我們知道如何實現這一目標。

You asked about differentiation to other medicines. These are often apples-to-oranges comparisons. We have looked at that, of course, and we really like the offering of xaluritamig. The patients treated on our study had quite advanced disease, even more advanced disease than the demographics of the patients as reported on other mechanism medicines such as radioligand therapies. And the response rates we're seeing are really clinically meaningful to patients, and that gives us great encouragement to develop the medicine more ambitiously in the next few years.

您詢問了與其他藥物的差異。這些通常是蘋果與橘子的比較。當然，我們已經研究過這一點，我們真的很喜歡 xaluritamig 的產品。我們研究中治療的患者患有相當晚期的疾病，甚至比其他機制藥物（例如放射性配體療法）報告的患者的人口統計數據更嚴重。我們看到的反應率對患者來說確實具有臨床意義，這極大地鼓舞了我們在未來幾年更加雄心勃勃地開發這種藥物。

Dave, in terms of the data sharing, do you want to share...

Dave，在數據共享方面，您想分享嗎...

Yes. In terms of data availability, as Jay mentioned, we're nearly complete in terms of dose expansion enrollment. So as those data roll forward over the course of the year, we'll provide guidance as to when we might have the next look at that data, but that's probably the next meaningful set of data. We'll get it looked at either later this year or early into next year.

是的。在數據可用性方面，正如傑伊所提到的，我們在劑量擴展註冊方面已接近完成。因此，隨著這些數據在一年中不斷滾動，我們將提供有關何時可能再次查看該數據的指導，但這可能是下一組有意義的數據。我們將在今年稍後或明年初對其進行研究。

Our next question comes from Tim Anderson from Wolfe Research.

我們的下一個問題來自沃爾夫研究中心的蒂姆·安德森。

So Eli Lilly today made a couple of sets of comments about this topic of GIP agonism versus antagonism and they also weighed in on the data you published yesterday. And I'm wondering, in as much as you heard that or read those comments, is there any context to add or anything that's actually incorrect or anything to refute? Because they covered quite a few points, and they continue to express their view, which is agonism is the best way, not antagonism.

因此，禮來公司今天就 GIP 激動與拮抗這一主題發表了幾組評論，他們也對您昨天發布的數據進行了權衡。我想知道，在您聽到或閱讀這些評論的同時，是否有任何需要添加的上下文或任何實際上不正確或需要反駁的內容？因為他們講了很多觀點，而且他們不斷表達自己的觀點，那就是競爭是最好的方式，而不是對抗。

Tim, this is Jay. Open it up to anyone else who wants to contribute to this. I don't believe that engaging in the dialogue around this adds much to the narrative. Rather, I'd say that the argument for GIP receptor antagonism comes from just the highest level of scientific data. The human experience across populations with 1 million patients studied, among those who have variation in the genes associated with this pathway, where that variation is directionally inhibitory, the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

提姆，這是傑伊。向任何願意為此做出貢獻的其他人開放。我不認為圍繞這個問題進行對話會為故事增添太多內容。相反，我想說 GIP 受體拮抗作用的論點僅來自最高程度的科學數據。研究了 100 萬名患者族群的人類經歷，在與該途徑相關的基因存在變異的人群中，如果這種變異是定向抑制性的，則 BMI 較低。因此，我們希望用這種藥物複製這種藥理學。我們對該領域的產品感到非常滿意。

Our next question comes from Robyn Karnauskas from Truist Securities.

我們的下一個問題來自 Truist Securities 的 Robyn Karnauskas。

This is Nicole on for Robyn. So on daxdilimab, targeting ILT7 with this, can you talk about your level of confidence in this target in light of the competitive landscape and what you expect to see near term from safety and efficacy?

這是妮可為羅賓代言的。那麼，對於 daxdilimab，針對 ILT7，您能談談您根據競爭格局對該目標的信心程度以及您對近期安全性和有效性的期望嗎？

Sure. Jay and Dave?

當然。傑伊和戴夫？

Yes. Well, it's very early days with this medicine. There's a strong preclinical support from the published literature and our own preclinical work. It's, nicely for patients, a very competitive landscape, but this is the earliest phases of clinical investigation. And so we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying.

是的。嗯，這種藥現在還處於早期階段。已發表的文獻和我們自己的臨床前工作提供了強有力的臨床前支持。對患者來說，這是一個競爭非常激烈的環境，但這是臨床研究最早的階段。因此，我們將以完全平衡的態度來解決這個問題，並將藥物帶給基於生物學基礎的患者，使他們能夠獲得最大的益處。

Yes. I would say the target, as you mentioned, is one that helps control some of the central signaling that drives some of the autoimmune diseases that are being investigated here. And at this point, I think it's all efforts towards generating the clinical data.

是的。我想說，正如您所提到的，目標是幫助控制一些中央訊號傳導的目標，這些訊號驅動一些正在研究的自體免疫疾病。在這一點上，我認為這一切都是為了產生臨床數據。

Our next question comes from James Shin from Deutsche Bank.

我們的下一個問題來自德意志銀行的 James Shin。

I have one for Jay. I just kind of want to piggyback on what Tim was alluding to. The GIP antagonism versus agonism, I'm looking at the Nature paper, it looks like 133's 420-milligram dose has a slight blip in triglycerides that eventually fades, but it does seem like antagonism is behaving a little differently from the literature for agonism. Is it too early to chalk it up to antagonism versus agonism in your view? Just wanted to get your thoughts there.

我有一份給傑伊。我只是想藉用蒂姆所暗示的內容。 GIP 拮抗作用與激動作用，我正在看《自然》雜誌上的論文，看起來133 的420 毫克劑量在甘油三酯方面有輕微的波動，最終會消失，但拮抗作用的表現確實與文獻中的激動作用略有不同。您認為現在將其歸因於對抗與激動是否還為時過早？只是想了解您的想法。

The short answer is it's too early to chalk it up to antagonism versus agonism. As I said before and I meant it, that these lipids are labile and indirect biomarker of this pharmacology. This is an early-stage study that had 1 or 3 monthly doses of the medicine. And so we are not reading anything into the lipids conclusively from this trial. We are making all these measurements in the active Phase II.

簡而言之，現在將其歸因於對抗與激動還為時過早。正如我之前所說，我是認真的，這些脂質是這種藥理學的不穩定和間接生物標記。這是一項早期研究，每月服用一到三個月的劑量。因此，我們並沒有從這次試驗中得出任何有關脂質的結論。我們正在積極的第二階段中進行所有這些測量。

Our last question will come from Carter Gould from Barclays.

我們的最後一個問題將來自巴克萊銀行的卡特·古爾德。

Maybe just one on 786. Can you walk through exactly what's sort of driving -- maybe let me take a step back. Maybe first, kind of if you could outline sort of how you're setting expectations there? And any color on what's driving the delay there? It seems like it's taking a long time to enroll 72 patients.

也許只是 786 上的一次。您能詳細介紹一下什麼是駕駛嗎？也許讓我退後一步。也許首先，您是否可以概述一下您如何在那裡設定期望？到底是什麼原因造成了延誤？招募72名患者似乎需要很長時間。

Sure. No, thank you for your question. For the broader group, AMG 786 is an oral medicine being developed for obesity. It is not an incretin that we've not as yet disclosed its target or pathway. This study is progressing fine. The readout of the Phase I is on track for the first half of 2024. We've completed initial dose escalation cohorts, and we're just collecting and analyzing data, expecting to read out in the first half of this year.

當然。不，謝謝你的提問。對於更廣泛的群體，AMG 786 是一種正在開發的針對肥胖症的口服藥物。它不是腸促胰素，我們尚未披露其標靶或途徑。這項研究進展順利。 I 期試驗預計將於 2024 年上半年公佈。我們已經完成了初始劑量遞增隊列，我們正在收集和分析數據，預計將在今年上半年公佈。

Great. And Julianne, we're going to turn it back to Bob for some closing remarks.

偉大的。朱麗安，我們將把它轉回給鮑勃做一些結束語。

Okay. Thank you all for joining the call. As you heard, we're excited about the opportunities that we see for growing our business across all 4 of our pillars: general medicine, oncology, inflammation and rare disease. Last October, we shared an in-depth look at oncology in connection with the ESMO medical meeting. And we plan to do an introductory review of rare diseases and our rare disease pillar in late February to give you more information about the medicines that we already have on the market as well as some of those that are advancing through our pipeline. So we're encouraged by the questions that we heard on this call about those molecules, and we're excited about them and their prospects. So we'll host a call, which IR will share with you here over the next few days, and look forward to having that opportunity. In the meantime, again, thank you for your support, and we look forward to talking to you at the Rare Disease Day or at our first quarter results call. Thank you.

好的。感謝大家加入通話。正如您所聽到的，我們對在所有 4 個支柱領域（普通醫學、腫瘤學、發炎和罕見疾病）發展業務的機會感到興奮。去年 10 月，我們在 ESMO 醫學會議上分享了腫瘤學的深入研究。我們計劃在 2 月下旬對罕見疾病和我們的罕見疾病支柱進行介紹性審查，以便為您提供有關我們市場上已有藥物以及正在通過我們的管道推進的一些藥物的更多信息。因此，我們對在這次電話會議中聽到的有關這些分子的問題感到鼓舞，我們對它們及其前景感到興奮。因此，我們將主持一次電話會議，IR 將在接下來的幾天內與您分享，並期待這樣的機會。同時，再次感謝您的支持，我們期待在罕見疾病日或第一季業績電話會議上與您交談。謝謝。

This concludes our 2023 Q4 earnings call. You may now disconnect.

我們的 2023 年第四季財報電話會議到此結束。您現在可以斷開連線。