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.

我叫朱莉安 (Julianne)，今天我將擔任安進 2023 年第四季財務業績電話會議的主持人。 （操作員指示）現在，我想介紹投資者關係副總裁賈斯汀·克萊斯 (Justin Claeys)。克萊斯先生，現在您可以開始了。

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 2023 年第四季財報電話會議。鮑勃·布拉德韋 (Bob Bradway) 將主持此次電話會議，隨後穆爾多·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；我很高興歡迎傑伊·布拉德納 (Jay Bradner)，這是他第一次參加我們的季度收益電話會議；和彼得·格里菲斯。 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.

考慮到 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 10 月 6 日以後 Horizo​​n 業務的貢獻。為避免疑問，這也將成為我們提交財務結果的基礎。為了補充這些信息，維克拉姆還將提供這些產品整個第四季度（包括 10 月第一周）的銷售信息，作為其講話的進一步背景信息。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了適當的對帳。我們也將做出一些前瞻性陳述，這些陳述受我們的安全港聲明的約束。請注意，實際結果可能會大不相同。

With that, over to you, Bob.

現在，就交給你了，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。謝謝你，賈斯汀，我也謝謝大家參加我們的電話會議。 2023年是安進公司又一個業績亮眼、不斷進步的一年，這將進一步幫助我們在本世紀末及以後實現可觀的成長。去年，我們四個季度的銷售量均實現了兩位數成長，並且各產品和地區均實現了均衡成長。我們有 18 種藥品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，這為我們帶來了重要的新罕見疾病業務，該業務現已成為我們與領先的普通醫學、腫瘤學和炎症業務並列的第四大增長支柱。

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.

我們收購的藥物都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技術、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可能惠及全球更多的患者。去年，我們也推進了公司歷史上最深入、最多樣化的產品線，其中涵蓋了我們四大成長支柱中處於各個開發階段的有前景的分子。我們預計今年將有十幾個重要的管道里程碑。我將談及其中幾點。

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這項資產的更多資訊。我們也在該領域推進了許多早期資產。

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 日根據 PDUFA 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腫瘤的雙特異性 T 細胞接合劑，對於這種腫瘤，幾十年來一直沒有新的治療方法，目前其 5 年存活率僅為 3%。我們正在研究塔拉單抗在早期治療中的應用，希望隨著時間的推移，能夠為美國和全球主要市場每年數以萬計被診斷為小細胞肺癌的患者提供服務。目前，我們已經非常成功地實現了這一目標，我們的第一個 BiTE，BLINCYTO，已經穩步進入急性淋巴細胞白血病的早期治療領域，我們將對另一個有前景的 BiTE，即前列腺癌的 xaluritamig，採取同樣的做法。

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 ROCKET 計劃中 8 項試驗中第一次試驗中 rocatinlimab 治療異位性皮膚炎的 III 期數據。在罕見疾病方面，我們將獲得 UPLIZNA 治療重症肌無力和 IgG4 相關疾病的 III 期數據。在全球人口快速老化需要更多創新的時代，安進公司正在透過目前市場上已有的藥物和正在研發的有前景的新藥來滿足人們的需求。

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科技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，我們一直在為這個關鍵時刻做準備，最近，我們任命戴夫·里斯 (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，而且在整個公司範圍內充分利用生成人工智能等技術。傑伊·布拉德納 (Jay Bradner) 接替戴夫擔任安進公司研發主管。傑伊是一名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 之前也曾擔任哈佛醫學院的教員，在加入安進公司之前，他是丹娜—法伯癌症研究所的執業腫瘤學家。我們很高興傑伊加入我們，並對他、戴夫和我們團隊其他成員將共同努力加速安進的創新，造福患者並促進我們業務的長期成長感到興奮。

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.

最後，我要感謝我們遍佈全球的 27,000 名員工，感謝他們為我們的成功做出的貢獻。現在我請 Murdo 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 年的表現非常滿意。全年產品銷售額較去年同期成長9%。銷量成長了 15%，各地區表現強勁。美國銷售成長率為 14%，歐洲、拉丁美洲、中東和加拿大地區的銷售成長率為 10%。亞太地區仍然是我們成長最快的地區，銷售成長率為 41%。這些結果包括 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.

我將從我們的普通醫藥業務開始，其中包括 Repatha、Prolia、EVENITY 和 Aimovig。這 4 款產品的總營收在第四季年增 15%，全年成長 17%，其中銷量分別成長 18% 和 20%。 Repatha 在第四季銷售額年增 25%，銷量成長 35%，但淨售價下降部分抵銷了這一成長。在美國以外，我們的銷量成長了 25%，各個地區的成長都表現強勁。

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，開始接受治療的新患者數量增加了 66%，帶動了 48% 的銷售成長。我們發現美國的淨售價下降，主要原因是新處方集的覆蓋範圍。我們預計此次額外的覆蓋將帶來強勁的銷售成長，足以抵消淨售價的下降。此外，一些付款人最近取消了部分患者的事先授權，這將進一步方便他們獲得 Repatha 的治療。

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教育醫生和患者降低 LDL-C 對減少心血管事件風險的重要性。在美國，我們在初級保健和心臟病學領域將於 2023 年聘用超過 20,000 名新的處方醫師。在我們對這項進展感到高興的同時，我們將繼續不懈努力，讓全世界更多患者能夠從 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.

轉向骨骼健康。 EVENITY 本季銷售額創下 3.18 億美元的紀錄，銷量成長了 39%。骨質疏鬆症對停經後婦女的影響尤其嚴重，此類患者的診斷和治療率較低。在美國，只有 6% 的極高風險骨質疏鬆症患者接受了骨骼治療，因此迫切需要一種有效的治療方法。 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利用人體自然能力增加骨骼形成並減少骨吸收的骨骼生成劑。我們看到 EVENITY 具有強大的成長潛力，我們將繼續運用我們在骨骼健康領域經過驗證的經驗，確保它能夠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。 10% 的體積增長得到了現實世界證據的支持，再次證明了對於未經治療且骨折風險較高的停經後骨質疏鬆症患者而言，與阿崙膦酸鈉相比，Prolia 在降低骨折風險方面具有優勢。

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，其中包括 BLINCYTO、LUMAKRAS、Vectibix、KYPROLIS、Nplate 和 XGEVA。第四季這6款創新產品的銷售額年增5%，銷量成長3%。受銷量成長 12% 的推動，全年銷售額年增 12%。 BLINCYTO 第四季銷售額年增 47%，達到創紀錄的 2.41 億美元。 55% 的銷售成長是由於對急性淋巴性白血病患者在一線鞏固治療中廣泛使用處方藥所致。從長遠來看，我們看到 BLINCYTO 作為誘導治療的一部分在前線早期使用中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更多適應症。第四季度，Vectibix 銷售額年增 5%，KYPROLIS 銷售額年增 8%，這均得益於銷量成長。

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.

Nplate 第四季銷售額年減 18%，主要由於美國政府下單時間導致銷量下降，但各地區銷售成長部分抵銷了這一下降。全年銷售額成長 13%，主要得益於包括美國政府訂單在內的銷售成長。不計美國政府訂單，Nplate 第四季銷售額年增 23%，全年銷售額年增 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。第四季度，Otezla 銷售額同比增長 2%，這得益於預計銷售扣除額的有利變化和 3% 的銷量增長，但庫存水平下降和淨售價下降部分抵消了這一增長。由於淨銷售價格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。在強勁執行力和投資增加的推動下，Otezla 的新患者數量在第四季度增長了 6%。競爭對手的禁毒計劃在本季的影響有所減弱。 Otezla 適用於所有嚴重程度的牛皮癬，且具有成熟的臨床特徵、廣泛的付款人覆蓋範圍、無需啟動檢測以及方便的口服給藥，因此在 2024 年及以後具有獨特的增長優勢。

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.

受預期銷售扣除額不利變化和淨售價下降 4% 的影響，Enbrel 第四季銷售額年減 8%。由於付款人覆蓋範圍擴大導致開始接受治療的新患者數量增加，美國第四季度的治療量增加了 1%。展望未來，我們預計，受更高的回扣以維持廣泛的一線付款人覆蓋範圍和患者結構的變化的影響，淨售價將繼續同比下降。

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 持續保持強勁的銷售軌跡，第四季銷售額達 1.77 億美元，全年銷售額達 5.67 億美元。受銷量成長推動，銷售額環比成長 10%。我們成功推出了自行管理的、預先填充的、一次性使用的注射筆，這使我們能夠將主要藥房福利管理者的覆蓋率擴大到 80% 以上，並隨著時間的推移促進了新患者的成長。展望未來，我們預計擴大覆蓋範圍將使 TEZSPIRE 能夠幫助更多患有嚴重無法控制的氣喘的患者。

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 本季的銷售額為 4,400 萬美元，全年銷售額為 1.34 億美元。第四季度，我們看到美國的銷售量較上季成長了 17%。展望未來，我們將繼續利用我們在腎臟病和發炎方面的專業知識，將 TAVNEOS 帶給更多的 ANCA 相關性血管炎患者。

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.

我們的生物相似藥產品組合的銷售額在第四季度同比增長 10%，全年增長 5%，其中銷量分別增長 27% 和 29%。銷量的成長被淨銷售價格的下降部分抵銷。隨著時間的推移，我們預計生物相似藥業務的長期成長將受到新分子的增加和額外產品的推出的推動。

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都很強勁，這突顯了我們為病患服務的根本承諾。我們的四大支柱產品使我們能夠為世界各地更多可受益於我們創新療法的患​​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，我將把主題交給維克拉姆 (Vikram)，他將負責我們的罕見疾病業務組合。

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，Murdo。我很高興與大家分享我們罕見疾病業務的最新進展，目前我們已經逾期 4 個月了。我們目前作為安進公司的一部分全面運營，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大支柱。我想確保您知道，我們沒有在新聞稿和幻燈片中報告整個季度的銷售額，該季度的銷售額反映了自 10 月 6 日以來的銷售額，總額為 9.54 億美元。這還不包括交易結束前 10 月第一週發生的 4,100 萬美元的銷售額。整個季度，我們來自 Horizo​​n 的罕見疾病品牌的產品銷售額為 9.95 億美元，年增 6%。在我的剩餘發言中，我將參考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，較上季成長3%。這是 TEPEZZA 連續第三個季度實現環比增長，增長主要受美國推動。

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.

我們繼續看到美國約有 10 萬名患有中度至重度疾病的患者可以從 TEPEZZA 中受益，其中大多數患者處於低臨床活動評分環境中。鑑於積極的領先指標和大量未滿足的需求，我們看到 TEPEZZA 在美國存在長期增長機會，同時也認識到我們的執行努力與實現患者數量增加之間存在一定的時間差。

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 來說也是一個有意義的長期成長機會。 TEPEZZA 已在巴西獲得批准，我們正在爭取在其他國家獲得批准。我們向日本和歐洲的擴張是重中之重，日本正在進行監管審查，歐盟則全年在進行備案。

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 是一種用於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的推動下，整個第四季度的銷售額創下了 2.8 億美元的記錄，同比增長 30%。目前年銷售額已達 10 億美元。績效是由患者旅程各個階段的執行情況、需求產生、利害關係人參與和治療依從性所驅動的。

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 領域成長最快的生物製劑，整個第四季的銷售額創下了 7,000 萬美元的紀錄，年成長 68%。隨著 UPLIZNA 逐漸在美國以外的多個市場推出，國際擴張也正在進行中。

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，主要得益於我們的超稀有藥物 RAVICTI、PROCYSBI 和 ACTIMMUNE。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，我們已準備好惠及比以往更多的患者。

I will now turn it over to Jay.

現在我將把話題交給傑伊。

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.

謝謝你，維克拉姆，大家下午好。我想花一點時間來表達我加入安進研發組織和領導團隊的激動之情。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，在加入之前我就已經很了解了。但現在作為安進的員工，我欣賞大家對面臨嚴重疾病的患者的強烈服務意識、志同道合的承諾、不斷擴大我們的藥品和業務的影響力，以及對這一潛在的首創和同類最佳藥品的卓越組合的共同信念。

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，我們在整個臨床管線中快速執行，在關鍵計畫中取得了出色的註冊率，並將 2024 年定為整個產品組合中具有改變患者護理潛力的藥物數據讀取量顯著的一年。 2023 年的主要亮點包括提供 4 種關鍵腫瘤學資產的有希望的數據以及獲得 3 項腫瘤學突破性治療指定。我們啟動了 tarlatamab 在小細胞肺癌治療、LUMAKRAS 在非小細胞肺癌和結直腸癌治療、以及 dazodalibep 在乾燥綜合徵治療的關鍵性 III 期研究。在普通醫學領域，如前所述，預計 2024 年底將獲得 592 名患者的 MariTide II 期研究的 52 週頂線數據。我們針對多種適應症的綜合性 III 期計畫仍在順利進行中。

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門的手稿，其中提供了 MariTide 臨床前和 I 期數據的整合。除了 MariTide 之外，我們的肥胖策略還涵蓋多項資產，其中 AMG 786 處於第一階段，其他臨床前資產正在推進中。我們的方法旨在滿足肥胖治療的動態需求，體現了我們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.

奧帕西崙是我們針對動脈粥狀硬化性心血管疾病的潛在最佳同類脂蛋白（a）小幹擾 RNA 分子，該藥物的 III 期結果研究已在全球招募了超過 7,000 名患者。僅用一年時間就在 34 個國家和 700 多個地點完成瞭如此快速的招募，凸顯了醫學界對奧帕西蘭的濃厚興趣和潛在影響。我們特意將最初的招募目標從 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區域監管要求。我們預計將於 2024 年上半年完成招生。

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達到較高確信度的目標，從而獲得較大的療效。我們很高興地宣布，FDA 已授予 BLINCYTO 用於治療早期 CD19 陽性 B-ALL 的優先審查權，PDUFA 日期為 2024 年 6 月 21 日。我們還計劃修改這項研究，以評估皮下注射 Blinatumomab 的效果，預計於 2024 年下半年開始，這將使我們能夠為更多的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》發表了一篇手稿，重點介紹了我們正在進行的 Ib 期研究的劑量擴展階段的數據，該研究以皮下注射 blinatumomab 作為單一藥物，治療接受過大量治療的複發/難治性 B 細胞 ALL 成年患者。在接受治療的 27 名可評估患者中，我們觀察到完全緩解率為 85%，其中 75% 為 MRD 陰性。皮下注射博納吐單抗耐受性良好，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。由於第二階段 DeLLphi-301 臨床試驗取得了令人鼓舞的結果並且 PDUFA 日期為 2024 年 6 月 12 日，FDA 授予了優先審查權。

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，目前正在研究治療轉移性去勢抵抗性前列腺癌，繼去年秋季公佈令人鼓舞的 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，預計在未來幾週內完成招募。我們已經啟動了一個減少的監測隊列，並在結合新型荷爾蒙療法的劑量範圍探索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.

對於口服 MTA 協同 PRMT5 抑制劑 AMG 193，我們在 7 種 MTAP 缺陷型實體瘤中觀察到 9 種反應，這令我們感到鼓舞。 AMG 193 是針對基因定義的合成致死性的藥物的絕佳範例，也是我們誘導接近平台的首次臨床轉化。我們目前正在迅速推進劑量擴展研究，並計劃在 2024 年上半年進入胸部和胃腸道惡性腫瘤的主方案，探索與標準治療的結合。

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 在嚴重氣喘以外適應症的應用，包括對伴有鼻息肉的慢性鼻竇炎和嗜酸性食道炎的單獨 III 期研究，預計在 2024 年下半年獲得頂線數據。我們也將繼續按計畫在 2024 年上半年展示第二階段 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.

我們針對 rocatinlimab（一種一流的抗 OX40 單株抗體）的 ROCKET III 期計畫已成功招募了 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，我們計劃今年啟動結節性癢疹的 III 期研究和氣喘的 II 期研究，以廣泛探索 rocatinlimab 的潛力。

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，我們對罕見疾病治療管道的進展感到鼓舞，其中包括幾個中後期治療機會。 12 月，TEPEZZA 在日本獲得孤兒藥資格，我們最近也向日本提交了 TEPEZZA 用於治療甲狀腺眼疾的新藥申請。為了服務日本的更多患者，我們正在針對臨床活動評分較低的慢性病環境進行 III 期研究。在日本以外，我們正在推進 TEPEZZA 皮下給藥，以推動更廣泛的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，我們預計今年將在重症肌無力和 IgG4 相關疾病方面獲得重要的 III 期數據，這兩種疾病都存在巨大的未滿足需求，我們有可能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，已進入乾燥症的 III 期治療。先前 II 期臨床試驗的數據顯示，該藥物對中度至重度全身性疾病患者以及症狀負擔較重的患者俱有療效，令人鼓舞。 Dazodalibep 是第一個被證明對後者患者群體有效的治療方法。在結束我們的罕見疾病研究工作時，我們對 fipaxalparant 感到非常興奮，fipaxalparant 是一種 LPAR1 拮抗劑，正在研究特發性肺纖維化，預計在 2024 年下半年獲得 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，並期待在 2024 年分享更多管道里程碑。

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。全年，我們實現總營收 282 億美元，年增 7%，非公認會計準則每股收益 18.65 美元，年增 5%。提醒一下，第四季度和全年業績均包括 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大約 1 週的 Horizo​​​​n 業績。在討論 2024 年的展望之前，我將回顧我們第四季度和全年財務表現的詳細資訊。

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.

我們第四季的總營收為 82 億美元。我們看到產品銷售額年增 20%，其中銷量成長 23%，但淨售價下降 3% 抵銷了這一成長。除去 Horizo​​n 的影響，產品銷售額年增 5%，主要得益於銷售成長 9%。全年總收入282億美元，年增7%。受銷售量15%成長的推動，產品銷售額年增9%。其他收入較去年同期下降 16%，主要原因是 2022 年與禮來公司在 COVID-19 方面的合作導致利潤下降和成本分攤減少。

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%.

嚴格的費用控制導致 2023 年全年非 GAAP 營業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，在我們的產品線中投資 47 億美元，並在收購 Horizo​​n 上投資 278 億美元。在第四季產品銷售量成長23%、全年成長15%的情況下，我們仍有效管理了業務的營運費用，第四季非GAAP營運費用年增18%，而全年非GAAP營運費用成長了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.

不包括 Horizo​​n 的影響，第四季非 GAAP 營業費用增加 3%，全年非 GAAP 營業費用增加 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增加1.1個百分點至17.0%。全年成長主要得益於利潤份額的提高和產品結構的變化，但從 2023 年開始波多黎各消費稅被所得稅取代部分抵消。

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 銷售、一般及行政費用年增 20%，主要由於與 Horizo​​n 收購相關的商業和一般及行政費用。全年非公認會計準則銷售、一般及行政費用年增 5%，主要由於與 Horizo​​​​n 收購相關的商業和一般及行政費用，但其他行銷產品支出的下降部分抵消了這一增長。第四季非公認會計準則下的營運、投資與支出 (OI&E) 約為 6.35 億美元，較去年同期增加 1.68 億美元，主要由於收購 Horizo​​​​n 而發行的債務相關的利息支出增加。全年非公認會計準則下的經營收益與淨利潤較上年同期相比增長 2.79 億美元，主要由於對百濟神州投資的會計處理改為公允價值按市價計價法，以及提前償還債務相關的收益，但淨利息支出增加部分抵消了這一影響。

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 GAAP 稅率在第四季度同比增加 2.5 個百分點至 15.9%，全年同比增加 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 2023 年產生了 74 億美元的自由現金流，而 2022 年為 88 億美元。我們預計，隨著 Horizo​​n 的加入，我們將繼續產生強勁的現金流，並正在按計劃實施我們的去槓桿計劃，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.

總而言之，我們將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 GAAP 研發費用增加了 8%，再加上 Horizo​​​​n Therapeutics 的收購，繼續拓寬和加強我們在治療領域的平衡產品組合。隨著我們強大的後期創新管道不斷推進，我們預計我們的非 GAAP 研發費用將在 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工廠。我們新的先進組裝和最終產品包裝工廠安進俄亥俄州 (Amgen Ohio) 剛剛於 1 月獲得 FDA 的商業生產許可，這距離我們破土動工約兩年，而我們在北卡羅來納州正在建設的創新藥物工廠預計將於 2026 年投入運營。第三，我們透過增加股利向股東返還資本，本季每股股利為 2.13 美元。這比 2022 年 4 個季度每季支付的金額增加了 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。預計 2024 年營收為 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。 我們有望實現先前提出的協同效應目標，即在交易完成後第三年或 2026 年實現至少 5 億美元的稅前成本。我們將記錄全年的傳統 Horizo​​n 產品銷售，我們預計我們的優先產品 Repatha、TEZSPIRE、EVENITY、Otezla、Prolia 和 BLINCYTO 將繼續受到銷售驅動而實現成長。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，當您模擬 2024 年第一季並且與我們的歷史趨勢一致時，我們預計由於福利計劃變化、保險重新驗證和共同支付費用增加，第一季的產品銷售額佔全年的百分比將是最低的。因此，我們預計 2024 年第一季的總營收將年增約 20%。我們預計全年其他收入將在約 13 億美元至 14 億美元之間。我們將繼續透過嚴謹的方法管理營運費用，以有效率地經營業務。

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，我們將加大研發投入，以支持我們有前景的後期產品線，包括 10 月份 ESMO 之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 的加入將對 2024 年的營業利潤率產生影響。

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 GAAP 營業利潤率成長在第一季之後的每季都會加速。

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，第一季的產品銷售量普遍較低，接下來的每季也是如此；第二，我們將繼續增加對商業品牌的支出，以 2023 年下半年進行的投資為基礎，包括 Repatha、Otezla 和我們的骨科產品組合 EVENITY 和 Prolia；第三，2024 年第一季反映了 Horizo​​n 的加入，鑑於收購截止日期為 10 月 6 日，我們正處於實現協同效應的初始階段。

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，我們預計第一季之後的每季的營業利潤率成長都會加速。我們預計，2024 年非 GAAP 銷售成本佔產品銷售額的百分比將介於 17% 至 18% 之間。考慮到全年的 Horizo​​n 相關費用，我們預計 2024 年的非 GAAP 研發費用將年增約 20%，同時投資也將增加以推進關鍵管道資產，包括 AMG 193、MariTide、rocatinlimab 和 tarlatamab。我們看到創新管道中存在的巨大潛力，重要的是我們現在進行策略性投資，以充分釋放未來的機遇，為病患、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 銷售、一般及行政開支，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 將在 26 億美元至 27 億美元之間。正如我們在 23 年第三季電話會議上提到的那樣，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支出。

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.

我們預計非公認會計準則稅率為 16% 至 17%。我們的指導主要受到兩個因素的影響。首先是收入的管轄組合，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律實體合理化，部分是為了將 Horizo​​n 實體整合到我們現有的總部位於美國的法律實體結構中。第二個好處是，像我們過去所做的那樣，透過按計劃向美國國稅局支付預付定金，可以阻止不確定稅務狀況的利息累積。在我們準備審判時，我們對與美國國稅局提出的法律論點的優點的信念沒有改變。

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，雖然存款對我們'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退還給我們，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審慎使用。再次，出於充分的明確考慮，這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，但隨著該框架繼續被更多司法管轄區考慮並且新規則生效，我們正在密切關注全球稅收狀況的未來影響。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的稅收來源，這可能會導致未來幾年稅收增加。

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 年股票回購額不會超過 5 億美元。我們預計 2024 年的資本支出約為 11 億美元，這與我們的資本配置重點一致，用於投資我們的業務，包括我之前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 年又取得了強勁的財務業績。財務更新到此結束。我感謝安進公司全球約27,000多名同事，感謝他們致力於服務病患的使命，並在2023年做出了不懈努力。

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

我會將問題交還給鮑伯進行問答。

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。讓我們開通熱線，並回答來電者的問題。朱利安，你為什麼不提醒他們這些程序，這樣我們就可以有效地為大家解答這些問題。

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

（操作員指示）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.

感謝良好的成績和良好的指導。我們有一個關於肥胖的問題。當然，133 號昨天已經發布了。我覺得這是最受關注的第一階段出版品。但也許您可以談談——也許傑伊可以談談您對一些標記的解釋，例如脂質、A1c、血壓等等。也許可以談談您對與競爭對手相比的概況的信心程度。

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。對於還沒看過的人來說，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，肥胖患者，BMI 大於 30。以 420 毫克劑量為例，這是劑量最高的研究，光是第 85 天體重就減輕了 14.5%。首先回答您的最後一個問題，我們發現第一階段的數據非常支持我們正在進行的工作，即開發這種藥物，以最大限度地造福肥胖症患者，我們很高興與社區分享這些數據。

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.

現在您已經詢問了有關研究中的一些測量數據、脂質、血壓和 A1c 的問題。我要提醒的是，這只是一項第一階段試驗，患者數量非常少，治療時間也相當短。但即使存在所有這些警告，雖然很難從如此小的數字中得出結論，尤其是血壓和脂質等不穩定的測量數據，但所有數據在方向上都是有利的。因此，我們對於該研究的這些測量結果毫不擔心。

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?

這裡還有另一個關於肥胖計畫的內容。那麼，在第一階段數據公佈之後，您如何看待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。我也要這個。您可能知道也可能不知道，目前正在進行的第二階段研究進展順利，探討了 11 個給藥組及相關的安慰劑對照。透過這項研究，我們將有機會獲得以不同方式更長時間接觸 MariTide 的經驗。我們最近為這項研究添加了第二部分，這將使我們能夠透過非常快速的招募來探索超過 52 週的更持久的減肥效果。這 4 個給藥組將繼續測試劑量水平以及比每月更低的給藥頻率。因此，即使到今年年底，這些 II 期數據也將對尋找安全、耐受且有效的劑量以進行 III 期臨床研究具有強烈的指導意義。

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。我唯一想補充的是，我們是從每月給藥節奏和時間表的基礎開始的。因此，額外的給藥組將研究每月以外的潛在給藥時間表。目前市場上的數據非常清晰。胃腸道毒性或胃腸道副作用通常與 GLP-1 的給藥日期有關，GLP-1 每週給藥一次。我們在劑量滴定的第一個劑量部分中看到了一些相同的胃腸道副作用。但這裡有一個機會，可以進一步延長給藥間隔，並進一步提高我們計劃的耐受性。正如傑伊清楚描述的，我們在第二階段計劃中研究了該問題的各個不同方面。

Our next question comes from Jay Olson from Oppenheimer.

下一個問題來自奧本海默公司的傑伊·奧爾森 (Jay Olson)。

Congrats on the progress. Another question on 133. Talk about whether or not the data 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?

祝賀你取得進展。關於 133 的另一個問題。您認為 133 可以每 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 部分的轉移率？

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

傑伊，你能抓住這一切嗎？傑伊問的一些問題在一開始就被分解了。

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.

第三部分和你的問題有些脫節。我聽到了對第 2 部分，即服藥頻率的更好的解釋。然後我就沒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.

如果您只是評論一下患者從第 1 部分轉到第 2 部分的比例。

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。讓我對第二部分的研究提供一些背景信息，我認為這將有助於回答這些問題。在第 2 部分中，我們的目的是真正觀察 52 週後的持久減肥效果。因此，透過持續的減肥，符合第二部分（從 52 週結束時開始）條件的患者將對這種藥物產生反應。然後他們將被重新隨機分配到 4 個隊列。這將測試劑量水平，並且再次測試這種頻率較低的給藥時間表。我們尚未披露給藥計劃的詳細細節。這是一個競爭的環境。但我們之所以有這個機會，是因為 ADC，即 MariTide 的抗體核心，就像許多免疫球蛋白療法一樣，讓我們有機會更少地使用它。隨著今年第二階段研究的持續進展，將確定轉入第二部分的患者比例。

Our next question comes from Chris Schott from JPMorgan.

下一個問題來自摩根大通的 Chris Schott。

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?

也許可以轉向 TEPEZZA 來提問。能稍微談談 2024 年的動態嗎？看起來產品又恢復成長了。但我只是想了解一下，既然安進現在擁有了這項資產，而且有更多的時間去利用它，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體？

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

當然。克里斯，也許我們可以把它分成幾個部分。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。感謝您的提問。我認為，如果你稍微關註一下推動 TEPEZZA 成長的根本因素，我們就會發現 TEPEZZA 的獨特處方數量創下了歷史新高。我們發現患者入院表格和患者開始數量增加。此外，我們在付款人覆蓋率方面取得了相當大的進展，因為我們看到我們的覆蓋率已經增加到美國覆蓋率的 50% 以上，這是非常重要的。透過向部分利害關係人普及新的臨床數據和更新的適應症，將繼續推動各類 TED 患者的接受度。最後，將所有這些結合在一起的是一個支持患者訪問的真正強大的患者服務模式。

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朝著每一個重要的領先指標努力。我們不應忘記，僅在美國，有資格使用這種藥物的患者大約只有 10 萬人，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.

這裡最後一點是，正如我們之前提到的，在實施所有這些努力和實現患者數量的增加之間仍然存在時間差。正如我們之前所說，從確定患者需要接受治療到該患者真正開始接受治療可能需要長達 90 天的時間。但我們對所有領先指標以及去年的執行感到非常滿意。

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，我唯一想補充的是，基於維克拉姆在準備好的發言中所說的，我們也對國際機會感到興奮。我認為他之前很好地描述了這一點。我們同樣對持續的投資創新以造福 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.

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?

我想特別談談 TEZSPIRE 在 COPD 中的作用。鑑於我們從 Dupixent 看到的相當有競爭力的數據，您打算如何實現差異化？那麼投資人該如何看待功效欄中的這些數據呢？這次試驗中是否存在需要澄清的細微差別，這可能會使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。 Murdo，我先開始，然後你再補充。這是一個非常好且及時的問題。 TEZSPIRE 的 II 期 COPD 研究，我們預計在今年上半年獲得數據。這是一項大型研究，涉及 337 名中度至重度 COPD 患者。儘管接受了三聯療法，他們的病情仍然惡化，這反映了目前 COPD 患者的需求尚未得到滿足，且治療不足。

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.

這個群體比我們在此研究的 Dupi 群體稍微廣泛一些。我們的讀數完全按照計劃進行。我們非常喜歡這裡的機制。你必須知道 TSLP 在上游起著訊號因子的作用。透過用我們獨特的生物療法阻斷它，我們可以阻斷 TSLP、IL-25、IL-33 訊號傳導。 TSLP 影響多種細胞類型，調節第 2 型氣道反應。透過打擊 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?

我們發現患者血清中的支氣管黏膜和支氣管肺泡灌洗液中TSLP升高。它由氣道上皮釋放。這種疾病的基礎生物學訊號顯示需要這種性質的藥物。透過觀察比 Dupi 更廣泛的人群，我們有機會真正弄清楚回應者是誰。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.

我認為您已經考慮到了所有基礎。埃文，我只想補充一點，正如傑伊所描述的，憑藉獨特而差異化的機制，我們希望能夠治療比目前可用的療法更廣泛的患者群體。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，如果我們在第三階段取得成功，我們就有條件將這樣的產品推向市場。

Our next question comes from Umer Raffat from Evercore ISI.

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.

我也想了解 AMG 133，有 2 個問題。首先，關於高劑量停藥的情況，我們知道 8 名患者中有 5 名沒有完成整個研究。但還有另一組患者也接受了 420 毫克的高劑量治療，但未見報告。這是一個有數位工具的工具。您能談談該組的停藥率嗎？這是單獨完成的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 280 毫克劑量導致肝酵素升高的病例，但該患者也感染了 COVID。能否談談肝酵素升高相對於 COVID 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，烏默爾。我目前無法提供第一階段研究的患者層面見解，但我非常感謝您的提問和對報告的興趣。我要談談 420 毫克劑量 I 期試驗的退出者，8 名患者中有 4 名退出了試驗。首先，值得注意的是，在多次遞增劑量中，接受 3 次 420 劑量的高劑量組在接受這 3 次每月劑量後真正實現了體重減輕，實際收益為 14.5%。事實證明，該組確實堅持到了第 150 天。不良事件和其他特徵與研究中的所有其他患者相當。現在關於數位團隊的第二個問題，我對此並不了解。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事回覆您。我不知道我們是否報告了停藥率的數據。

Our next question comes from Colin Bristow from UBS.

下一個問題來自瑞銀的科林布里斯托。

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.

也許在 MariTide 上還有更多。首先，您能否提供一些有關劑量的見解？我的意思是，顯然這些劑量相當大。如果我們看一下——例如 Repatha 420 毫克需要 5 分鐘以上的輸注或連續注射 3 次。所以我想知道您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 似乎比競爭分子更傾向於 GLP。那麼，您是否認為最終的臨床特徵將與長效 GLP-1 與競爭對手的 GLP 更為相似？

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。首先我想說，我不認為這些劑量很高。我是新來的。但對於一種勝肽抗體比例為 2:1 的抗體藥物偶聯物生物治療藥物來說，420 毫克似乎在現代生物治療產品範圍內。我不需要告訴這個密切關注安進的社區，這是一個非常複雜的生物治療組織，在製造方面，我們每次都為每一位患者提供藥物，並且我們擁有所有必要的能力，以這三種或其他劑量和時間表提供這種藥物。所以我完全不用擔心。

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藥廠開發的藥物之間的區別，即從機制上講，MariTide 的核心抗體抑制了 GIP 受體，而其他這些肽類藥物則使其激動。我們對抑制該受體的選擇感到非常放心，因為現有的最精細的實驗數據、自然實驗表明，在非常大的群體中開展的全基因組關聯研究表明，需要、也有機會抑制GIP受體以降低BMI，正如在該受體和下游信號通路中的差異所觀察到的，這些差異與大量群體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.

至於您所問的 GIP 受體抑制與 GLP-1 激動之間的平衡，在人類身上很難測量。但我們的模型表明，透過我們觀察到的治療劑量和暴露，我們可以實現兩者。

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，我是默多。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，我們在這方面做了大量工作，我們期待患者至少在每月的服藥計劃中得到非常積極和簡單的體驗。具體來說，我們從 Repatha 中學到了很多東西，並且還會對 Repatha 進行更多的跟踪，但我們將繼續致力於改善患者對生物注射的體驗。

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.

就在我們進入下一個問題的時候，請注意，我們已經快到我們實際預留的時間了，因為我知道我們仍然有相當多的問題在等待回答。因此，我們會嘗試讓每個來電者提出一個問題，然後解決。我們會繼續排隊等待我們的電話或問題，但我知道你們中的一些人可能不得不退出。

Our next question comes from Yaron Werber from TD Cowen.

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 Brendan 代替 Yaron 上場。實際上，這只是我們的一個簡短回答。根據您目前看到的數據以及您聽到的一些醫生的回饋，這是關於 UPLIZNA 的。考慮到所有的競爭，您認為 UPLIZNA 在 MG 治療模式中處於什麼位置？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 只討論一下 NMOSD 目前產品的效能，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 well 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 在 NMOSD 確實發展得相當好。如您所知，它現在是 NMOSD 中成長最快的生物製劑。我們將繼續在多個方面採取行動。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，並且適合我們所處的競爭環境。因此該產品持續表現良好。我認為我們希望繼續在 NMOSD 中很好地執行這種藥物。傑伊，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。您可能知道，我是血液學家。我認為 CD19 是一個極好的目標。它實際上在所有 B 細胞上表達，並保留在漿細胞上。因此，考慮到適應症擴大，正如您所問的，有大量疾病可以透過 UPLIZNA 進行治療，為尚未滿足需求的患者帶來真正的益處，遠遠超出目前僅針對 B 細胞子集的 CD20 的應用。我們的團隊並沒有忽略這一點，目前我們正在努力確定適應症擴展的優先事項。

Our next question comes from Mohit Bansal from Wells Fargo.

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 皮下注射有一個疑問。您確實有計劃啟動第三階段研究。您能否稍微談談您使用哪種技術？這是與現有的 Halozyme 技術相關的嗎？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實現皮下注射 TEPEZZA。

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 subQ.

也許我會直接加入。我們剛才說我們將繼續進行 subQ。

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

下一個問題來自美國銀行的 Geoff Meacham。

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?

另一個是 133。這是尚未滿足的需求嗎？ 133 是否具有分化潛力？至於時間安排，您是否希望掌握第二階段的資料？或者這是您可以採取的一種有風險的措施嗎？

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。眾所周知，肥胖是一個重大的公共衛生危機，大約 40% 的美國人的體質指數超過 30，這會造成巨大的成本，給全球第三方支付者和社會帶來沉重的負擔。與肥胖相關的疾病名單很長，包括心血管疾病和心臟衰竭、2 型糖尿病、阻塞性睡眠呼吸中止症、NASH、NAFLD、腎臟疾病。這些慢性疾病確實需要能夠持久減肥的藥物。所以，我們認為，如您所知，我們在第二階段計劃中為這些肥胖相關疾病提供了非常強大的解決方案。肥胖有很大的遺傳因素。我們根據基因見解鎖定了 GIPR 抑制。所以機會空間還是比較大的。您問的是指示是什麼，甚至可能是按照什麼順序。當我們獲得所有必要的數據時，我們會適時發表評論。但我們意圖透過一切跡象表明這種雙重機制可以改善公眾健康。我們正在積極規劃並按計劃開展廣泛的第三階段計劃。

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

就……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。我認為——傑夫，這是戴夫·里斯。我想補充一點，我們正在規劃一個非常廣泛的第三階段計畫。因此，您可以期待看到多個跡象同時向前發展。正如傑伊所說，當我們開始看到數據時，我們將開始啟動這些試驗並進行討論。此外，如您所知，世界各地的監管機構都要求在第三階段啟動之前提供一定數量的安全資料。因此，我們當然會遵守這項規定。但我們的目標是，一旦獲得必要的資料集和監管部門批准，就盡快啟動第三階段。

Our next question comes from David Risinger from Leerink Partners.

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，請問一下。您能否進一步說明您對 II 期臨床試驗對血壓和脂質影響的預期，特別是您是否預期這些指標具有與 tirzepatide 類似的療效？

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，但我現在不會試圖預測藥理學的結果。正如您在我們的第一階段計劃中看到的，這種藥物耐受性很好，可以帶來持久的減肥效果，並且不會使某些測量值出現明顯偏差。我只是認為現在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.

而您能得到的最佳推論是根據剛發布的臨床前數據。我建議您看一下。

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 Yige 代替 Michael 上場。關於 xaluritamig 的快速介紹。您能談談今年數據公開的計劃，以及目前對潛在註冊路徑的思考嗎？您如何看待這種藥物相對於其他一些基於不同機制的新興藥物（如前列腺癌中的 ADC 或 AR 降解劑）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。感謝你提出這個出色的問題，邁克爾。 xaluritamig 是一種非常有趣且令人興奮的分子。對於通話中的人來說，這是一個 STEAP1 CD3 雙特異性。我們一直在研究晚期去勢抵抗性前列腺癌。我們已經擴大了一個研究隊列，即 I 期單一療法研究。我們正在減少監測，以及正如您所提到的現有和新型雄激素受體調節劑整合劑。我們也正在探索與該領域的新型藥劑的結合。

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.

該計劃的當前重點是建立減少監控。這對於讓所有患者受益非常重要。我們正在研究減少監測的可行性。我們在這些 T 細胞雙特異性抗體方面擁有豐富的經驗，並且具有門診治療的可能性。

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.

監管路徑的方法將會適時出現。那裡不會有任何意外。值得慶幸的是，為去勢抵抗性前列腺癌患者提供單獨或最終聯合用藥的途徑已經很成熟，而且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.

您詢問的是與其他藥物的區別。這些往往是蘋果和橘子之間的比較。當然，我們已經考慮過這個問題，我們真的很喜歡 xaluritamig 的產品。我們研究中接受治療的患者的病情都相當嚴重，甚至比其他機制藥物（如放射性配體療法）報告的患者病情更為嚴重。我們看到的反應率對患者來說確實具有臨床意義，這給了我們很大的鼓勵，讓我們在未來幾年更有雄心地開發這種藥物。

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

戴夫，就數據共享而言，你想分享嗎...

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，我們的劑量擴展招募工作已基本完成。因此，隨著這些數據在一年內不斷向前滾動，我們將提供指導，說明何時可以再次查看這些數據，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年初對此進行研究。

Our next question comes from Tim Anderson from Wolfe Research.

我們的下一個問題來自 Wolfe Research 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 factually 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 激動作用與拮抗作用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評估。我想知道，當您聽到或讀到這些評論時，是否有任何背景資訊需要補充，或者有任何事實上不正確的內容或任何需要反駁的內容？因為他們談了不少觀點，而且他們不斷表達自己的觀點，那就是鬥爭才是最好的方式，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 a 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。向任何想要為此做出貢獻的人開放。我不認為圍繞這個問題進行對話能為敘事帶來多大幫助。相反，我認為 GIP 受體拮抗劑的論點僅僅來自於最高等級的科學數據。研究人員對一百萬人群進行了研究，結果表明，在與該通路相關的基因發生變異的人群中，如果這種變異受到方向性的抑制，那麼他們的 BMI 較低。因此我們希望用這種藥物複製這種藥理作用。我們對這個領域的貢獻感到非常高興。

Our next question comes from Robyn Karnauskas from Truist Securities.

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 Nicole，代表 Robyn 發言。那麼，對於以 ILT7 為目標的 daxdilimab，您能否根據競爭格局談談您對該目標的信心程度，以及您對近期安全性和有效性的預期？

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，這種藥物的應用還處於早期階段。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領域，但這只是臨床研究的早期階段。因此，我們將以完全平衡的方式處理這個問題，並根據潛在的生物學原理為患者提供最有可能受益的藥物。

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，這個目標有助於控制一些驅動正在研究的一些自體免疫疾病的中心訊號。在這一點上，我認為所有的努力都是為了產生臨床數據。

Our next question comes from James Shin from Deutsche Bank.

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.

我有一個給傑伊。我只是想附和一下蒂姆所暗示的事情。關於 GIP 拮抗作用與激動作用，我正在查看《自然》雜誌的論文，看起來 133 的 420 毫克劑量會使甘油三酯出現輕微波動，但最終會消失，但拮抗作用的表現似乎與激動作用的文獻略有不同。您認為將其歸結為對抗與鬥爭是否為時過早？只是想聽聽你的想法。

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，現在將其歸結為對抗與競爭還為時過早。正如我之前所說，這些脂質是不穩定的，並且是這種藥理學的間接生物標記。這是一項早期研究，藥物劑量為每月 1 或 3 次。因此，我們無法從這次試驗中對脂質做出任何結論性的解讀。我們在第二階段的積極行動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.

也許只有一個關於 786 的問題。首先，您能否概述一下您是如何設定期望的？有什麼具體原因導致延遲嗎？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。對於更廣泛的群體來說，AMG 786 是一種針對肥胖症開發的口服藥物。它不是一種腸促胰島素，我們至今仍未揭示其目標或途徑。這項研究進展順利。第一階段的讀數預計將在 2024 年上半年完成。

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

偉大的。朱麗安，我們將把話題轉回給鮑勃，讓他做一些結束語。

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。感謝大家參加此次電話會議。正如您所聽到的，我們對在四大支柱領域（普通醫學、腫瘤學、發炎和罕見疾病）發展業務的機會感到非常興奮。去年 10 月，我們在 ESMO 醫學會議上分享了腫瘤學的深入探討。我們計劃在二月底對罕見疾病和罕見疾病支柱進行一次介紹性審查，以便為您提供更多有關我們已經在市場上銷售的藥物以及一些正在研發的藥物的資訊。因此，我們對在這次電話會議上聽到的有關這些分子的問題感到鼓舞，我們對它們和它們的前景感到興奮。因此，我們將召開一次電話會議，IR 將在接下來的幾天裡在這裡與您分享，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。