美國安進 (AMGN) 2023 Q3 法說會逐字稿

My name is Julianne, and I will be your conference facilitator today for Amgen's Third Quarter 2023 Financial Results Conference Call.

我叫朱莉安，今天我將擔任安進公司 2023 年第三季財務業績電話會議的主持人。

(Operator Instructions)

（操作說明）

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

現在我謹介紹投資者關係副總裁賈斯汀‧克萊斯先生。克萊斯先生，您可以開始了。

Thank you, Julianne, good morning and welcome to our third 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, who joined Amgen from Horizon Therapeutics following the October 6, 2023 acquisition close; Dave Reese; and Peter Griffith.

謝謝朱莉安，早安，歡迎參加我們2023年第三季財報電話會議。鮑勃·布拉德韋將主持本次電話會議，隨後默多·戈登、維克拉姆·卡納尼（他在2023年10月6日完成對Horizo​​​​n Therapeutics的收購後加入安進）、戴夫·里斯和彼得·格里菲斯將對我們的業績進行更廣泛的回顧。

Given the timing of the Horizon Therapeutics acquisition close, our third quarter results do not include any contribution from Horizon. Vikram will provide select information from Horizon's third quarter product sales for future context. You should have received a link to our slides that we have posted. Through the course of our discussion today, we will make some forward-looking statements and use non-GAAP financial measures to describe our performance. And just a reminder that actual results can vary materially.

鑑於Horizo​​​​n Therapeutics收購完成的時間，我們第三季的業績不包含Horizo​​​​n的任何貢獻。 Vikram將在後續報告中提供Horizo​​​​n第三季產品銷售的部分資訊。您應該已經收到我們發布的幻燈片連結。在今天的討論中，我們將做出一些前瞻性陳述，並使用非GAAP財務指標來描述我們的績效。再次提醒，實際結果可能與預期有重大差異。

I would now like to turn the call over to Bob.

現在我想把電話交給鮑伯。

Okay. Thank you, Justin, and thank all of you for joining our call. It's an exciting time here at Amgen and we're continuing to execute well this year, serving many more patients around the world with medicines such as Repatha, EVENITY and TEZSPIRE, advancing a number of promising first-in-class medicines rapidly through our pipeline and preparing for our next wave of biosimilar launches.

好的。謝謝賈斯汀，也謝謝各位參加我們的電話會議。安進正處於令人興奮的發展階段，今年我們將繼續保持良好的業績，透過瑞百安（Repatha）、EVENITY 和 TEZSPIRE 等藥物為全球更多患者提供服務，同時快速推進多款極具前景的首創藥物的研發，並為下一波生物類似藥的上市做好準備。

However, as this is our first earnings call, following the close of our acquisition of Horizon Therapeutics, I thought we might turn our attention there first.

然而，由於這是我們完成對 Horizo​​​​n Therapeutics 的收購後的第一次財報電話會議，我認為我們應該先把注意力集中到那裡。

The Horizon acquisition, coupled with our purchase of ChemoCentryx, which we acquired a little more than a year ago, gives Amgen a significant rare disease business that fits squarely within our overall strategy and will be additive to the growth we expect from our base business. At the heart of our strategy, of course, is innovation. First, our best-in-class medicines that make a big difference for patients suffering from serious diseases. The medicines in our rare disease portfolio like TAVNEOS, TEPEZZA, KRYSTEXXA and UPLIZNA fit this description perfectly, and they'll benefit from Amgen's decades of experience in inflammatory diseases. These medicines are also early enough in their life cycles that we can positively impact their growth by leveraging Amgen's capabilities in process development, life cycle management and manufacturing.

收購Horizo​​n，加上我們一年多前收購的ChemoCentryx，使安進在罕見疾病領域擁有了重要的業務，這與我們的整體策略高度契合，並將對我們基礎業務的預期成長起到積極作用。當然，我們策略的核心是創新。首先，我們擁有業界領先的藥物，能夠為嚴重疾病的患者帶來顯著的改變。我們罕見病產品組合中的藥物，例如TAVNEOS、TEPEZZA、KRYSTEXXA和UPLIZNA，完美符合這一描述，並將受益於安進在炎症性疾病領域數十年的經驗積累。這些藥物目前仍處於生命週期的早期階段，我們可以利用安進在製程開發、生命週期管理和生產方面的能力，積極推動其成長。

Finally, we spent the past decade or so building out our international footprint with Amgen medicines now available in about 100 countries. And today, our rare disease sales come almost exclusively from the U.S. So we'll be able to leverage our global presence to quickly bring these medicines to patients around the world. You'll hear more in a minute from Vikram Karnani, who joined us through the Horizon acquisition and is leading a newly created rare disease business that is now the fourth leg of Amgen's commercial stool alongside our inflammation, oncology and general medicine businesses.

最後，在過去的十年左右時間裡，我們不斷拓展國際商業版圖，安進的藥品現已在全球約100個國家上市。如今，我們的罕見疾病藥物銷售幾乎全來自美國。因此，我們將能夠充分利用我們的全球佈局，並迅速將這些藥物帶給世界各地的患者。稍後您將聽到Vikram Karnani的更多介紹，他透過收購Horizo​​​​n加入我們，並領導新成立的罕見疾病業務部門。該部門如今已成為安進商業版圖的第四大支柱，與我們的發炎、腫瘤和普通內科業務並駕齊驅。

Turning to our financial performance in the quarter. Total revenues were up 4% and earnings per share were up 6% compared with a year ago. Volume increased 11% globally, which represents our fourth consecutive quarter of double-digit volume growth, and we achieved good balance across all of our geographic regions and therapeutic areas. Seven of our medicines generated record sales in the quarter, and I'll highlight one of these, BLINCYTO, which delivered 55% sales growth in the third quarter.

接下來談談本季的財務表現。總營收年增4%，每股收益較去年同期成長6%。全球銷量成長11%，這是我們連續第四個季度實現兩位數的銷售成長，並且在所有地區和治療領域都實現了良好的平衡。本季度，我們有七款藥品創下了銷售紀錄，其中我特別要提到BLINCYTO，其第三季銷售額成長了55%。

We see continued upside potential for BLINCYTO as it is increasingly used in earlier lines of therapy and as practice guidelines are updated to reflect the role this medicine can play in treating a broad range of patients with acute lymphoblastic leukemia.

我們看到 BLINCYTO 具有持續的上漲潛力，因為它越來越多地用於早期治療，實踐指南也在更新，以反映這種藥物在治療各種急性淋巴細胞白血病患者中可以發揮的作用。

Turning to our pipeline. We had the opportunity to discuss 6 potential first-in-class oncology assets with you recently following ESMO. Three of these have earned breakthrough therapy designations from the FDA, tarlatamab, BLINCYTO and LUMAKRAS in combination with Vectibix in colorectal cancer. We also continue to progress trials for bemarituzumab in gastric cancer for Xaluritamig in prostate cancer and for AMG 193, our PRMT5 inhibitor which has generated responses across 6 solid tumors.

接下來談談我們的研發管線。在最近的ESMO大會之後，我們有機會與您探討了6項潛在的首創腫瘤藥物。其中三項已獲得FDA授予的突破性療法認定，分別是tarlatamab、BLINCYTO以及LUMAKRAS合併Vectibix用於治療大腸直腸癌。此外，我們也持續推進bemarituzumab用於治療胃癌、Xaluritamig用於治療前列腺癌以及AMG 193（一種PRMT5抑制劑，已在6種實體瘤中顯示出療效）的臨床試驗。

I'll just quickly note that AMG 193 was identified through our proprietary DNA-encoded library technology which we added through the 2019 acquisition of New Evolution, and it demonstrates our leadership in the emerging field of multi-specific drugs that can address pathways that have long been recognized but considered inaccessible to traditional drug discovery efforts.

我只想快速指出，AMG 193 是透過我們專有的 DNA 編碼庫技術發現的，該技術是我們透過 2019 年收購 New Evolution 而獲得的，它表明我們在多特異性藥物這一新興領域處於領先地位，這些藥物可以解決長期以來人們已經認識到但傳統藥物發現方法認為無法觸及的通路。

In other pipeline news, we've completed enrollment in our Phase II obesity study from Maridebart cafraglutide, which is formerly known as AMG 133. And finally, the FDA has accepted our BLA for a biosimilar to EYLEA.

在其他研發管線方面，我們已完成 Maridebart cafraglutide（原名 AMG 133）的 II 期肥胖症研究的患者招募。最後，FDA 已受理我們 EYLEA 生物相似藥的生物製品許可申請 (BLA)。

Looking at our business, we feel we have good momentum across the board. We have everything we need with the portfolio, the pipeline and the people to deliver attractive sales and earnings' growth through the end of the decade and beyond. As always, I want to thank Amgen employees around the world, including some 2,000 new colleagues focused on rare diseases for their commitment to strong execution on behalf of the patients we serve.

縱觀公司業務，我們認為目前各方面都發展勢頭良好。憑藉完善的產品組合、在研產品線和優秀人才，我們已具備在未來十年乃至更長時間內實現可觀的銷售和盈利增長的條件。一如既往，我要感謝安進全球的員工，特別是約2000名專注於罕見疾病領域的新同事，感謝他們為服務患者所做的卓越貢獻。

With that, I'll now turn over to Murdo Gordon. Murdo?

接下來，我將把麥克風交給默多‧戈登。默多？

Thanks, Bob. I'm pleased with our performance in the third quarter. Execution is strong across the business with record quarterly sales for 7 brands and robust volume growth across our general medicine, inflammation and hematology/oncology portfolios. Product sales increased 5% year-over-year. Volume growth was 11% with strength across our regions. U.S. volume growth was 11% and volume growth in our Europe, Latin America, Middle East and Canada region was 8%. Consistent with our international expansion strategy, Asia Pacific continues to be our fastest-growing region with 27% volume growth in the quarter.

謝謝，鮑伯。我對我們第三季的業績非常滿意。公司各業務部門的執行力都很強勁，7個品牌的季度銷售額均創歷史新高，普通內科、發炎和血液/腫瘤產品組合的銷量也實現了強勁增長。產品銷售額較去年同期成長5%。銷量成長11%，各區域均表現強勁。美國地區的銷量成長11%，歐洲、拉丁美洲、中東和加拿大地區的銷量成長8%。亞太地區持續維持成長最快的地位，本季銷售成長27%，這與我們的國際擴張策略相符。

Starting with our General Medicine business, which includes Repatha, Prolia, EVENITY and Aimovig. Overall revenue for these 4 products grew 21% year-over-year in the third quarter, driven by 20% volume growth. Repatha sales increased 31% year-over-year in the third quarter with volume growth of 44%, partially offset by lower net selling price. In the U.S., volume growth of 45% was driven by a record number of new patients starting treatment more than doubling year-over-year. We saw declining net selling prices in the U.S., primarily driven by new formulary coverage by CVS in July for commercial patients.

首先來看我們的一般內科業務，其中包括瑞百安（Repatha）、普羅利亞（Prolia）、依維寧（EVENITY）和艾莫維（Aimovig）。這四款產品的總營收在第三季年增21%，主要得益於銷售量成長20%。瑞百安第三季的銷售額年增31%，銷量成長44%，但部分被淨售價下降所抵銷。在美國，銷售量成長45%，主要得益於新患者人數創下歷史新高，較去年同期成長超過一倍。在美國，淨售價下降，主要原因是CVS在7月將部分產品納入商業保險患者的健保報銷範圍。

Outside the U.S., we saw 43% volume growth with strength across our regions. There are still many more patients around the world who can benefit from Repatha. And we're rising to meet that challenge by investing and executing to drive awareness amongst physicians and patients. In the U.S., we have significantly expanded our primary care sales force and activated more than 15,000 new prescribers this year. We're also increasing promotion to patients through direct-to-consumer media efforts.

在美國以外地區，我們的銷售量成長了43​​%，各區域均表現強勁。全球仍有眾多患者能夠從瑞百安（Repatha）中獲益。為了應對這項挑戰，我們正加大投入並積極推動相關工作，以提高醫生和患者的認知度。在美國，我們已大幅擴充了初級保健銷售團隊，並在今年新增了超過15,000名處方醫生。此外，我們也透過面向消費者的媒體管道，加大了對病患的推廣力道。

Transitioning to bone health, Prolia sales grew 14% year-over-year in the third quarter, primarily driven by 7% volume growth and higher net selling price. We expect volumes for Prolia to grow, supported by real-world evidence data presented earlier this year that demonstrate Prolia's superiority in reducing fracture risk when compared to alendronate in treatment-naive patients with postmenopausal osteoporosis.

在骨骼健康領域，Prolia 第三季銷售額年增 14%，主要得益於銷量成長 7% 和淨售價上漲。我們預計 Prolia 的銷售將持續成長，這得益於今年稍早公佈的真實世界證據數據。這些數據表明，與阿崙膦酸鈉相比，Prolia 在降低停經後骨質疏鬆症初治患者的骨折風險方面具有優勢。

EVENITY had record sales of $307 million for the quarter, driven by 48% volume growth. Osteoporosis disproportionately impacts postmenopausal women and the diagnosis and treatment rates for these patients are low. In 2023, we expect approximately 3 million patients in the U.S. will be treated for postmenopausal osteoporosis. An estimated 40% of treated patients will be at very high risk of fracture, but at least 6% of those high-risk patients will be treated with a bone-building product.

EVENITY本季銷售額創下3.07億美元的紀錄，銷售量成長48%。骨質疏鬆症對停經後女性的影響尤其嚴重，而這些患者的診斷率和治療率卻很低。我們預計，到2023年，美國將有約300萬停經後骨質疏鬆症患者接受治療。據估計，接受治療的患者中約有40%面臨極高的骨折風險，但至少有6%的高風險患者將接受骨骼強化產品的治療。

EVENITY plays an important role in the bone-builder market with a 58% share in the U.S. and a 44% share in Japan. There's much more work to be done, and we'll continue to invest to ensure EVENITY reaches the patients who need it.

EVENITY在骨骼強化劑市場中扮演重要角色，在美國的市佔率為58%，在日本的市佔率為44%。我們還有很多工作要做，並將繼續投資，以確保EVENITY能夠惠及真正需要的患者。

Otezla sales declined 10% year-over-year, driven by lower net selling price, unfavorable changes to estimated sales deductions and lower inventory levels, partially offset by 1% volume growth in the U.S. Otezla net price declines were driven by higher rebates to support and expand access for commercial and Medicare Part D patients. Our U.S. Otezla business has been impacted by free drug programs associated with new treatment options that have entered the psoriasis marketplace.

受淨售價下降、銷售預估扣減不利變化以及庫存水準降低的影響，Otezla 的銷售額年減 10%，但美國市場 1% 的銷售成長部分抵銷了這些不利影響。 Otezla 淨售價下降是由於提高了回扣，以支持和擴大商業保險和聯邦醫療保險 D 部分 (Medicare Part D) 患者的用藥管道。我們在美國 Otezla 的業務受到了與新進入銀屑病治療市場的新療法相關的免費藥物計劃的影響。

We're beginning to see a reduced impact of these free drug programs as physicians and patients are experiencing barriers to access given prior authorization requirements for these newer therapies. We have strong conviction in the growth potential of Otezla. With this unique 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. To realize that potential, we have increased our investment to ensure physicians and patients understand both the importance of treating psoriasis systemically and the safety and efficacy profile that Otezla offers.

由於這些新型療法需要事先審批，醫師和病患在取得藥物方面面臨許多障礙，我們開始看到這些免費藥物計畫的成效有所下降。我們對 Otezla 的成長潛力充滿信心。 Otezla 具有獨特的適應症，適用於所有嚴重程度的銀屑病，並擁有成熟的臨床數據、廣泛的醫保覆蓋、無需進行任何檢查即可開始治療以及便捷的口服給藥方式。為了充分發揮這一潛力，我們已加大投入，以確保醫生和患者了解系統性治療銀屑病的重要性，以及 Otezla 的安全性和有效性。

We're already seeing positive results from that increased investment, including significant growth in the number of patients requesting educational information and taking action on the Otezla website that generally indicate preparation for a discussion with a health care professional. We've also recently increased our dermatology sales force by 20% to educate physicians about the benefits of Otezla for appropriate patients. With these increased investments, we expect to drive a return to growth for Otezla.

我們已從增加的投資中看到積極成果，包括索取教育資訊並在 Otezla 網站上採取行動的患者數量顯著增長，這通常表明他們已做好與醫療專業人員討論的準備。此外，我們最近還將皮膚科銷售團隊擴充了 20%，以便向醫生普及 Otezla 對合適患者的益處。隨著這些投資的增加，我們預計 Otezla 將重回成長軌道。

ENBREL sales decreased 6% year-over-year, primarily driven by an 8% decline from unfavorable changes to estimated sales reductions. Year-over-year volume increased 1% in the third quarter, and the number of new patients in the U.S. starting treatment increased by 22% driven by improved payer coverage and ENBREL's 20-plus year track record of safety and efficacy. For the remainder of 2023, we expect our improved coverage will lead to continued growth in new patients and declining net selling price.

恩利（ENBREL）銷售額較去年同期下降6%，主要原因是預期銷售額下降幅度不利，導致銷售額下降8%。第三季銷量較去年同期成長1%，美國新病患人數成長22%，這得益於健保覆蓋範圍的擴大以及恩利20多年來安全性和有效性的良好記錄。我們預計，在2023年剩餘時間內，健保覆蓋範圍的擴大將持續推動新病患人數成長，並導致淨售價下降。

TEZSPIRE continues to show strong growth with $161 million in sales in the third quarter. Sales increased 21% sequentially driven by 18% volume growth that benefited from the launch of our self-administered prefilled, single-use pen, which was approved by the U.S. Food and Drug Administration in the first quarter. We've now obtained coverage of the pen with the majority of pharmacy benefit managers, enabling easy access and convenient self-administration for patients in the U.S. with severe uncontrolled asthma.

TEZSPIRE第三季銷售額達1.61億美元，持續保持強勁成長動能。銷售額較上季成長21%，主要得益於銷售成長18%，而銷售成長則得益於我們第一季獲得美國食品藥物管理局（FDA）核准的預填充式單次注射筆的上市。目前，該注射筆已獲得大多數藥品福利管理機構的醫療覆蓋，使美國重度未控制氣喘患者能夠輕鬆便捷地獲得並自行注射。

As we expected, TEZSPIRE has both penetrated and helped to grow the U.S. asthma biologics market. In 2023, the number of new patients on asthma biologics has increased by over 20% year-over-year, and TEZSPIRE share of this expanded market is approximately 20%.

正如我們預期的那樣，TEZSPIRE 成功打入並推動了美國氣喘生物製劑市場的成長。 2023 年，接受氣喘生物製劑治療的新患者人數較去年同期成長超過 20%，TEZSPIRE 在這一擴大的市佔率約為 20%。

Sales of TAVNEOS were $37 million in the quarter with 26% quarter-over-quarter volume growth. In the U.S., approximately 2,300 patients have now been treated with TAVNEOS by over 1,500 health care professionals. We continue to see an increase in awareness of TAVNEOS by rheumatologists and nephrologists. And exiting the quarter, we saw an increase in new patient start forms.

本季TAVNEOS的銷售額為3,700萬美元，季增26%。在美國，已有超過1500名醫護人員使用TAVNEOS治療了約2,300名患者。我們持續看到風濕病學家和腎臟病學家對TAVNEOS的認知度不斷提高。此外，本季末，新患者申請表數量也有所增加。

Looking forward, we expect to bring TAVNEOS to even more patients with ANCA-associated vasculitis. AMJEVITA sales increased 30% year-over-year for the third quarter, driven by 53% volume growth, partially offset by lower net selling price. Ex U.S. sales increased 10% driven by 22% volume growth, partially offset by lower net selling price.

展望未來，我們期望將TAVNEOS帶給更多ANCA相關性血管炎患者。 AMJEVITA第三季銷售額年增30%，主要得益於銷售量成長53%，但部分被淨售價下降所抵銷。美國以外地區的銷售額成長10%，主要得益於銷售成長22%，但部分被淨售價下降所抵銷。

Moving to our hematology/oncology business, which includes LUMAKRAS, KYPROLIS, XGEVA, Vectibix, Nplate and BLINCYTO. Strong commercial execution and compelling new clinical data drove 15% volume growth year-over-year for these 6 innovative products. BLINCYTO sales grew 55% year-over-year to a record $220 million for the third quarter. Volume growth of 56% was supported by broad prescribing to acute lymphoblastic leukemia patients following positive data from the registration-enabling E-1910 study presented late 2022 and updated NCCN guidelines that were issued in May. Long term, we see significant additional growth potential for BLINCYTO from earlier lines of therapy.

接下來談談我們的血液/腫瘤業務，其中包括LUMAKRAS、KYPROLIS、XGEVA、Vectibix、Nplate和BLINCYTO。強勁的商業執行力和令人信服的新臨床數據推動這六款創新產品銷售量年增15%。 BLINCYTO第三季銷售額年增55%，創下2.2億美元的紀錄。銷售量成長56%主要得益於在2022年底公佈的註冊支持性E-1910研究的積極數據以及5月份發布的NCCN更新指南的推動下，該藥物被廣泛用於治療急性淋巴細胞白血病患者。從長遠來看，我們認為BLINCYTO在早期治療領域具有巨大的成長潛力。

LUMAKRAS reported $52 million in sales for the third quarter, a decline of 31% year-over-year. $22 million of this decline was driven by ongoing reimbursement negotiations in France. We see future growth opportunities for LUMAKRAS driven by launches in new markets and our comprehensive global clinical development program.

LUMAKRAS第三季銷售額為5,200萬美元，較去年同期下降31%。其中2200萬美元的下降是由於法國正在進行的醫保報銷談判所致。我們認為，隨著新市場的推出以及我們全面的全球臨床開發計劃，LUMAKRAS未來將迎來成長機會。

Vectibix sales increased 2% year-over-year for the third quarter to a record $252 million, driven by higher net selling price and 4% volume growth, partially offset by unfavorable foreign exchange impact.

Vectibix 第三季銷售額年增 2%，達到創紀錄的 2.52 億美元，主要得益於淨售價上漲和銷售成長 4%，但部分被不利的匯率影響所抵銷。

KYPROLIS grew 10% year-over-year, primarily driven by 8% volume growth. And Nplate sales increased 45% year-over-year for the third quarter, resulting from $142 million order from the U.S. government. In the fourth quarter, we expect to fulfill an additional $62 million order for Nplate by the U.S. government.

KYPROLIS 年成長 10%，主要得益於銷量成長 8%。 Nplate 第三季銷售額年增 45%，主要得益於美國政府 1.42 億美元的訂單。我們預計第四季將完成美國政府另一筆價值 6,200 萬美元的 Nplate 訂單。

Given the strong performance of our hematology/oncology products and the exciting new positive data presented at ESMO on our oncology pipeline, we look forward to helping more patients with their cancer therapy. Overall, our execution is strong across the business, driving growth and demonstrating our dedication to serving patients. And with the expansion of our rare disease portfolio, we're excited to serve many more patients around the world who can benefit from our therapies.

鑑於我們血液腫瘤產品的強勁表現，以及在ESMO大會上公佈的腫瘤產品線令人振奮的積極新數據，我們期待著幫助更多癌症患者獲得治療。整體而言，我們在整個業務領域的執行力強勁，推動了成長，並展現了我們服務患者的決心。隨著罕見疾病產品組合的擴展，我們很高興能夠為全球更多受益於我們療法的患者提供服務。

And with that, I'll turn it over to Vikram.

接下來，我將把麥克風交給維克拉姆。

Thanks, Murdo. We're excited to bring together Horizon's medicines, pipeline and rare disease expertise with Amgen's history of leadership in inflammatory diseases, global infrastructure and world-class biologic capabilities. For those that are not as familiar with Horizon's portfolio, I will spend the next few minutes providing some background on our rare disease medicines.

謝謝，默多。我們很高興能將Horizo​​​​n的藥物、研發管線和罕見疾病領域的專業知識與安進在發炎性疾病領域的領先地位、全球基礎設施和世界一流的生物製劑能力相結合。對於不太了解Horizo​​​​n產品組合的朋友，我將在接下來的幾分鐘中簡要介紹我們的罕見疾病藥物。

Horizon's business delivered $945 million of sales in the third quarter representing 2% year-over-year sales growth with multiple positive leading indicators. Let me describe in more detail. TEPEZZA, the first and only medicine approved for the treatment of thyroid eye disease regardless of disease activity or duration generated $453 million of sales in the third quarter representing 2% quarter-over-quarter growth. We are confident that now as we have officially joined forces and have onboarded the full commercial team, we will make significant progress in advancing this important product over time to patients. We are driving several initiatives to continue to build the U.S. thyroid eye disease market.

Horizo​​n公司第三季銷售額達9.45億美元，年增2%，並取得多項積極的領先指標。下面我將詳細介紹。 TEPEZZA是首個也是目前唯一核准用於治療甲狀腺眼疾（無論疾病活動度或病程長短）的藥物，第三季銷售額達4.53億美元，較上季成長2%。我們相信，隨著我們正式合併並組建完整的商業團隊，我們將在推進這項重要產品的上市過程中取得顯著進展，最終惠及更多患者。我們正積極推動多項舉措，以持續拓展美國甲狀腺眼疾市場。

In the third quarter, we saw a greater than 50% year-over-year increase in the number of TEPEZZA prescribers, supported by the April 2023 FDA label update to treat patients with thyroid eye disease regardless of disease activity or duration. We are pleased with this progress and are continuing to educate the physician community on new clinical data and updated indication across the full spectrum of TED patients.

第三季度，TEPEZZA處方醫生數量年增超過50%，這得益於FDA於2023年4月更新的藥品標籤，該標籤允許TEPEZZA用於治療甲狀腺眼疾患者，無論其疾病活動度或病程長短。我們對這項進展感到欣慰，並將繼續向醫生群體普及新的臨床數據和更新的適應症，涵蓋所有類型的甲狀腺眼疾患者。

Second, large national and regional payers are continuing to make favorable policy changes to help eligible patients access TEPEZZA. To date, we have obtained favorable policy changes for greater than 30% of U.S. covered lives, which are expected to take effect later this year and early next year. As a reminder, for TEPEZZA, there's a time lag between a patient being identified for TEPEZZA treatment and treatment being initiated. It can take up to 90 days for a patient enrollment form to move through the prior authorization process. Once that step is complete, then the patient's infusion needs to be scheduled at an appropriate site of care. This process takes time, and we have taken several important steps to minimize the time between patient identification and treatment initiation.

其次，大型全國性和區域性醫療保險機構正在持續調整政策，以幫助符合條件的患者獲得TEPEZZA治療。迄今為止，我們已為超過30%的美國參保人群爭取到有利的政策調整，預計將於今年稍後和明年年初生效。需要提醒的是，TEPEZZA治療從確定患者符合治療條件到開始治療之間存在時間差。病患登記表可能需要長達90天的時間才能完成預先授權流程。一旦完成該步驟，就需要安排患者在適當的醫療機構進行輸液。這個過程需要時間，我們已採取多項重要措施，以盡可能縮短從確定患者符合治療條件到開始治療的時間。

Finally, we continue to see approximately 100,000 patients with moderate-to-severe disease in the U.S. that are appropriate for TEPEZZA, with the majority of these patients in low clinical activity score settings. Therefore, the patients -- the FDA's label update, combined with favorable medical policy changes by payers and supported by the expanding base of prescribing physicians gives us a significant opportunity to reach more patients. These positive execution trends underpin our confidence in TEPEZZA's growth potential in the U.S.

最後，我們仍然看到美國約有10萬名中重度疾病患者適合使用TEPEZZA，其中大多數患者的臨床活動評分較低。因此，患者群體、FDA的藥品標籤更新、支付方有利的醫療政策變化以及不斷擴大的處方醫生群體，為我們提供了惠及更多患者的絕佳機會。這些正面的進展趨勢增強了我們對TEPEZZA在美國市場成長潛力的信心。

Moving on to markets outside the U.S. We continue to see international expansion as a meaningful long-term growth opportunity for TEPEZZA, which received its first ex U.S. approval in Brazil in the second quarter of this year. We are particularly excited about the opportunity to leverage Amgen's long-standing presence in multiple major ex-U.S. markets including Europe and in Japan, where we have reported positive data from the Phase III OPTIC-J trial.

接下來，我們展望美國以外的市場。我們仍然認為國際擴張是TEPEZZA重要的長期成長機會。 TEPEZZA於今年第二季度在巴西獲得了美國以外的首個上市許可。我們特別興奮的是，有機會利用安進在包括歐洲和日本在內的多個美國以外主要市場的長期佈局。在日本，我們已公佈了OPTIC-J III期臨床試驗的積極數據。

We also continue to enroll a TEPEZZA Phase III trial in Japanese patients with chronic or low clinical activity thyroid eye disease.

我們也將繼續招募患有慢性或低臨床活動性甲狀腺眼疾的日本患者參與 TEPEZZA III 期試驗。

KRYSTEXXA, the first and only medicine approved for uncontrolled gout delivered a record $253 million of sales in the third quarter, representing 32% year-over-year growth. Sales are now annualizing at a $1 billion run rate. Performance in the third quarter reflected continued strong uptake in both the rheumatology and nephrology segments. Strong results were driven by execution across all phases of the patient journey, demand generation, stakeholder education and adherence to treatment. The FDA approved KRYSTEXXA's label change for combination with methotrexate in July 2022. We have seen a steady increase in uptake since then.

KRYSTEXXA是首個也是目前唯一獲準用於治療難治性痛風的藥物，第三季銷售額創下2.53億美元的紀錄，年增32%。目前，該藥的年化銷售額已達10億美元。第三季的業績反映了風濕病和腎臟病領域持續強勁的市場需求。強勁的業績得益於在病患就醫全程、需求開發、利害關係人教育以及治療遵從性等方面的出色執行。 FDA於2022年7月批准了KRYSTEXXA與甲胺蝶呤聯合用藥的適應症變更。自此以來，該藥的市場需求持續成長。

Immunomodulation usage remained above 70% of new patient starts in the third quarter. We see an opportunity to redefine KRYSTEXXA with methotrexate as the standard of care and reach even more of the over 100,000 uncontrolled gout patients in the U.S.

第三季度，免疫調節劑的使用率在新患者仍維持在70%以上。我們看到了一個機會，可以將KRYSTEXXA（以甲胺蝶呤為標準療法）重新定義為一種治療方案，從而惠及美國超過10萬名未控制痛風患者。

UPLIZNA sales increased 54% year-over-year in the third quarter to $67 million. International expansion is also underway with UPLIZNA now launched in multiple ex U.S. markets, including Germany, France, Italy, Spain and Brazil. Additional indications in development also support UPLIZNA's long-term growth potential with Phase III trials underway in both IgG4-related disease and Myasthenia Gravis.

UPLIZNA第三季銷售額年增54%，達到6,700萬美元。 UPLIZNA的國際擴張也在進行中，目前已在包括德國、法國、義大利、西班牙和巴西在內的多個美國以外的市場上市。此外，UPLIZNA在IgG4相關疾病和重症肌無力方面的III期臨床試驗正在進行中，這些正在研發中的適應症也為其長期成長潛力提供了支持。

The rest of Horizon's portfolio generated $173 million of sales in the third quarter, primarily driven by our portfolio of ultra rare medicines, RAVICTI, PROCYSBI and ACTIMMUNE. We see an opportunity for this basket of products to continue to generate robust sales.

Horizo​​n其他產品組合在第三季創造了1.73億美元的銷售額，主要得益於我們的罕見疾病藥物組合，包括RAVICTI、PROCYSBI和ACTIMMUNE。我們認為這一系列產品有望持續保持強勁的銷售動能。

Before I turn it over to Dave Reese, I want to take the opportunity to thank all my colleagues in the rare disease business for maintaining their focus on patients throughout a period of distraction over the last several months. Looking ahead, we are excited to work together by leveraging Amgen and Horizon's combined capabilities to ensure our medicines reach more patients even faster who are suffering from serious and rare diseases globally.

在將發言權交給戴夫·里斯之前，我想藉此機會感謝所有罕見疾病領域的同事，感謝他們在過去幾個月裡，儘管面臨諸多幹擾，仍然始終專注於患者。展望未來，我們很高興能夠攜手合作，充分利用安進和Horizo​​​​n的綜合實力，確保我們的藥物能夠更快地惠及全球更多患有嚴重罕見疾病的患者。

I'll now turn it over to Dave.

現在我把麥克風交給戴夫。

Thank you, Vikram, and good morning, everyone. I'd like to begin by welcoming our new colleagues from Horizon. We're excited to be integrating Horizon's R&D capabilities with Amgen's to advance the promising Horizon pipeline. For R&D, the third quarter was one of high-quality execution as we progressed our innovative pipeline with important oncology data readouts, the addition of 2 breakthrough therapy designations and completion of enrollment on key studies. We also advanced our innovative pipeline through rapid enrollment on multiple registration-enabling studies.

謝謝Vikram，大家早安。首先，我謹代表安進歡迎來自Horizo​​​​n的新同事們。我們很高興能將Horizo​​​​n的研發能力與安進的研發能力結合，共同推動Horizo​​​​n前景廣闊的研發管線。在研發方面，第三季我們有效率地執行，並且取得了顯著進展。我們取得了重要的腫瘤學數據，新增兩項突破性療法認定，並完成了關鍵研究的患者招募。此外，我們也透過快速招募多項註冊研究的患者，推動了創新研發管線的進展。

Starting with general medicine. We have completed enrollment in the Phase II study of Maridebart cafraglutide in patients with obesity with or without diabetes. The goal of this study is to generate data that will provide optionality to design a broad Phase III program, leveraging the unique properties of Maridebart cafraglutide that could potentially allow us to take a differentiated approach. We anticipate topline data from this 52-week study towards the end of 2024.

首先，我們已完成針對肥胖症（伴隨或不伴隨糖尿病）患者的 Maridebart cafraglutide II 期研究的患者招募。研究旨在收集數據，以便我們設計一項廣泛的 III 期臨床試驗方案，充分利用 Maridebart cafraglutide 的獨特特性，從而採取差異化的治療策略。我們預計將於 2024 年底獲得這項為期 52 週研究的主要數據。

The Phase III outcome study of Olpasiran, our potentially best-in-class Lp(a) targeting small interfering RNA molecule in atheroscrotic cardiovascular disease is enrolling very well. In inflammation, beyond severe asthma, we are investigating additional indications with TEZSPIRE including separate Phase III studies in chronic rhinosinusitis with nasal polyps, which is fully enrolled and eosinophilic esophagitis. We also have a Phase II study in COPD that is in fully enrolled with topline data anticipated in the first half of 2024. This study has recruited a broad population of COPD patients, including patients with both high and low eosinophil counts.

針對動脈粥狀硬化性心血管疾病，我們潛在的同類最佳的靶向Lp(a)的小幹擾RNA分子Olpasiran的III期療效研究正在順利進行中。在發炎領域，除了重度氣喘之外，我們也正在利用TEZSPIRE探索其他適應症，包括慢性鼻竇炎伴鼻息肉（已完成全部入組）和嗜酸性食道炎的獨立III期研究。此外，我們還有一項針對慢性阻塞性肺病（COPD）的II期研究，該研究已完成全部入組，預計將於2024年上半年公佈主要數據。該研究納入了廣泛的COPD患者群體，包括嗜酸性粒細胞計數高低不同的患者。

Our rocatinlimab, a first-in-class anti-OX40 monoclonal antibody being investigated in patients with moderate to severe atopic dermatitis, recruitment is off to a strong start on the ROCKET Phase III clinical development program.

我們的 rocatinlimab 是一種首創的抗 OX40 單株抗體，目前正在對中度至重度異位性皮膚炎患者進行研究，其在 RO​​CKET III 期臨床開發項目中的招募工作已取得良好開端。

We have now randomized over 1,500 patients across the program. We are excited to present additional data from our expanded rheumatology portfolio following the acquisition of Horizon including data from a Phase II study of Dazodalibep and Sjogren syndrome, along with data from KRYSTEXXA, TAVNEOS, Otezla and other molecules from our broad portfolio at the American College of Rheumatology Convergence 2023 meeting in November.

目前，我們已在該項目中隨機分配了超過 1500 名患者。我們很高興能在 11 月舉行的 2023 年美國風濕病學會年會上，展示收購 Horizo​​​​n 後我們擴展的風濕病產品組合的更多數據，包括 Dazodalibep 治療乾燥綜合徵的 II 期研究數據，以及 KRYSTEXXA、TAVNEOS、Otezla 和我們廣泛產品組合中的其他分子的數據。

I'll be brief with my remarks on our oncology portfolio, given the detailed oncology review last week. Based on the E-1910 Phase III study, the FDA has granted BLINCYTO breakthrough therapy designation for the treatment of adult and pediatric patients with CD19 positive, Philadelphia chromosome-negative, B-cell precursor acute lymphoblastic leukemia during the consolidation phase of multiphase therapy. We see future growth of BLINCYTO from advancements into earlier lines of therapy and subcutaneous administration. BLINCYTO also serves as a blueprint for how we plan to rapidly progress tarlatamab and Xaluritamig into earlier lines of therapy and setting a lower tumor burden.

鑑於上週已對我們的腫瘤產品組合進行了詳盡的審查，我將簡要介紹一下。基於E-1910 III期研究，FDA已授予BLINCYTO突破性療法認定，用於治療CD19陽性、費城染色體陰性、B細胞前體急性淋巴細胞白血病成人和兒童患者，用於多階段治療的鞏固期。我們預計BLINCYTO未來將透過推進至更早期的治療方案和皮下給藥途徑而獲得成長。 BLINCYTO也為我們如何快速推進tarlatamab和Xaluritamig在更早期的治療方案中應用以及降低腫瘤負荷提供了藍圖。

Along with experts in the field, we are very encouraged by tarlatamab, our BiTE molecule targeting DLL3. At ESMO, we presented data from DeLLphi-301, a Phase II study in late stage small cell lung cancer where we saw impressive response rates, durability of response and overall survival in a setting where patients typically have limited options and a very poor prognosis. We are submitting these data to the FDA and are pleased that the FDA has granted tarlatamab breakthrough therapy designation for the treatment of adult patients with extensive stage small cell lung cancer with disease progression on or after platinum-based chemotherapy. Given our confidence in these data, we are rapidly advancing tarlatamab into earlier lines of treatment with multiple Phase III studies underway or planned.

我們與該領域的專家一樣，對靶向DLL3的BiTE分子tarlatamab充滿信心。在ESMO大會上，我們發表了DeLLphi-301研究的數據。這是一項針對晚期小細胞肺癌的II期臨床研究，結果顯示tarlatamab具有令人矚目的緩解率、緩解持久性和總生存期，而這類患者的治療選擇通常有限，預後極差。我們已將這些數據提交給FDA，並欣喜地得知FDA已授予tarlatamab突破性療法認定，用於治療接受鉑類化療後疾病進展的廣泛期小細胞肺癌成人患者。鑑於我們對這些數據的信心，我們正迅速推進tarlatamab在早期治療中的應用，目前正在進行或計劃開展多項III期臨床研究。

Based on emerging clinical data, we are discontinuing PSMA-targeting bispecific AMG 340, and we'll focus our efforts on rapidly advancing Xaluritamig in metastatic castrate-resistant prostate cancer. We expect Xaluritamig dose expansion cohorts to be fully enrolled by the end of the year and are planning to initiate additional studies in patients with earlier stage prostate cancer.

基於新出現的臨床數據，我們將停止PSMA靶向雙特異性抗體AMG 340的研發，並將專注於快速推進Xaluritamig在轉移性去勢抵抗性前列腺癌的應用。我們預計Xaluritamig劑量擴展隊列研究將於年底前完成全部入組，並計劃啟動更多針對早期前列腺癌患者的研究。

With AMG 193, a small molecule MTA cooperative PRMT5 inhibitor, we're encouraged by the responses we've seen across 6 MTAP Null solid tumors, the manageable safety profile and preclinical evidence of CNS penetrant. We're now rapidly enrolling dose expansion cohorts.

AMG 193 是一種小分子 MTA 協同 PRMT5 抑制劑，我們對其在 6 種 MTAP 缺失型實體瘤中的療效、可控的安全性以及中樞神經系統穿透性的臨床前證據感到鼓舞。目前，我們正在快速進行劑量擴展隊列研究。

And with that, I'll turn things over to Peter for the financial update.

接下來，我將把財務最新情況交由彼得來報告。

Thank you, Dave. I'll review our third quarter results before discussing our updated 2023 guidance. Turning to our third quarter financial results, which are shown on Slide 44. Total revenues of $6.9 billion grew 4% year-over-year and non-GAAP earnings per share of $4.96 grew 6% year-over-year. The growth in revenues was due to product sales increasing 5% year-over-year, driven by 11% volume growth.

謝謝戴夫。在討論我們更新後的2023年業績指引之前，我會先回顧一下我們第三季的業績。現在來看看第三季的財務業績，具體數據請見第44頁投影片。總營收為69億美元，年增4%；非GAAP每股收益為4.96美元，較去年同期成長6%。營收成長主要得益於產品銷售額年增5%，而產品銷售額的成長又主要由11%的銷售成長所驅動。

Third quarter total non-GAAP operating expenses increased 4% year-over-year. We advanced our pipeline and invested in growth opportunities in the quarter while delivering a non-GAAP operating margin as a percent of product sales of 52%. Non-GAAP cost of sales as a percent of product sales increased 1.3 percentage points on a year-over-year basis to 17.4%, primarily driven by higher profit shares and changes in product mix. Non-GAAP R&D expenses in the quarter decreased 2% year-over-year due to lower spend in research and early pipeline activities, partially offset by higher spend in later-stage clinical programs and marketed products.

第三季非GAAP總營運費用年增4%。本季度，我們推進了產品線研發並投資於成長機會，同時實現了52%的非GAAP營運利潤率（佔產品銷售額的百分比）。非GAAP銷售成本佔產品銷售額的百分比年增1.3個百分點至17.4%，主要受利潤分成比例提高和產品組合變動的影響。本季非GAAP研發費用年減2%，主要原因是研發和早期產品線活動的支出減少，但部分被後期臨床項目和已上市產品的支出增加所抵銷。

Year-to-date, non-GAAP R&D expenses increased 5% due to higher spend in later-stage clinical programs and marketed products, partially offset by lower spend in research and early pipeline. Non-GAAP SG&A expenses in the third quarter increased 1% year-over-year. We continue to focus on prioritizing key investments, digitalization, driving productivity and accelerating use cases for artificial intelligence. Non-GAAP OI&E were a net $225 million expense in the third quarter.

今年迄今為止，非GAAP研發費用成長5%，主要原因是後期臨床計畫和已上市產品的支出增加，但部分被研究和早期管線支出減少所抵銷。第三季非GAAP銷售、管理及行政費用年增1%。我們將繼續專注於優先進行關鍵投資、數位轉型、提高生產力以及加速人工智慧的應用。第三季非GAAP營運、投資及支出淨額為2.25億美元。

The year-over-year favorability was driven primarily by higher interest income and the change in Beijing accounting from equity methods to mark-to-market investments with the impact included only in our GAAP results. Our third quarter non-GAAP tax rate increased 3.2 percentage points to 16.1%, primarily due to the 2022 Puerto Rico tax law change that replaced the excise tax with an income tax beginning in 2023.

年比業績成長主要得益於利息收入增加以及北京會計準則下投資核算方法由權益法改為市值法，但該影響僅體現在我們的GAAP業績中。第三季非GAAP稅率上升3.2個百分點至16.1%，主要原因是波多黎各2022年稅法變更，該變更將消費稅替換為所得稅，並於2023年開始實施。

We continue to execute on our capital allocation priority. First, we continue to prioritize investments in both internal and external innovation. In the third quarter, we increased investments in programs, including Maridebart cafraglutide, I'll call it Mari from now on; rocatinlimab; TAVNEOS; and ABP-206, our biosimilar; to Opdivo. Second, we continue investing in our business for long-term growth including through simultaneous construction of our state-of-the-art manufacturing facilities in Ohio and North Carolina. We're excited for the anticipated licensure of our Ohio facility in the first half of 2024. Additionally, we're making investments in all parts of our business to leverage the power of generative AI opportunities.

我們繼續推進資本配置優先事項。首先，我們持續優先投資內部和外部創新。第三季度，我們增加了對多個項目的投資，包括 Maridebart cafraglutide（以下簡稱 Mari）、rocatinlimab、TAVNEOS 以及 Opdivo 的生物相似藥 ABP-206。其次，我們繼續投資於業務的長期成長，包括同時在俄亥俄州和北卡羅來納州建造最先進的生產設施。我們對俄亥俄州工廠預計將於 2024 年上半年獲得許可感到非常興奮。此外，我們正在對業務的各個方面進行投資，以充分利用人工智慧生成技術帶來的機會。

Third, we have a strong track record of returning capital to our shareholders and paid dividends of $2.13 per share in the third quarter, representing a 10% increase over the third quarter in 2022. The company generated $2.5 billion of free cash flow in the third quarter of 2023 compared with $2.8 billion in the third quarter of 2022. We will continue to generate strong cash flows. However, Q4 cash flow will be lower than historical patterns due to the timing of tax payments and Horizon transaction-related expenses.

第三，我們擁有向股東返還資本的良好記錄，第三季派發了每股2.13美元的股息，較2022年第三季增長10%。該公司2023年第三季自由現金流為25億美元，而2022年第三季為28億美元。我們將繼續保持強勁的現金流。然而，由於稅款支付時間和與Horizo​​​​n交易相關的費用，第四季度現金流將低於歷史水準。

Turning to the outlook for the business for 2023 on Slide 46. We're pleased to have closed the acquisition of Horizon Therapeutics. We're updating our full year 2023 guidance to include Horizon financial results starting October 6, 2023. So our Q4 results will exclude approximately 1 week of Horizon's results. We are raising our 2023 revenue guidance to $28.0 billion to $28.4 billion versus previous guidance of $26.6 billion to $27.4 billion. For 2023 non-GAAP earnings per share, we are narrowing the range to $18.20 to $18.80 versus previous guidance of $17.80 to $18.80. We will add Horizon's business into Q4 without material non-GAAP EPS dilution.

請參閱第46頁投影片，以了解2023年的業務展望。我們很高興完成了對Horizo​​​​n Therapeutics的收購。我們將更新2023年全年業績預期，納入Horizo​​​​n自2023年10月6日起公佈的財務業績。因此，我們的第四季業績將不包含Horizo​​​​n約一週的業績。我們將2023年營收預期上調至280億美元至284億美元，先前預期為266億美元至274億美元。對於2023年非GAAP每股收益，我們將預期範圍縮小至18.20美元至18.80美元，此前預期為17.80美元至18.80美元。我們將把Horizo​​​​n的業務納入第四季度業績，不會對非GAAP每股收益造成重大稀釋。

However, we do expect Q4 non-GAAP EPS to be lower than Q3 non-GAAP EPS because of planned investment increases in our business, including key assets in our innovative pipeline beginning with Mari, Olpasiran and AMG 193 and other strategic business investments, including generative AI use cases in all parts of our business. This sequential pattern is consistent with historical trends.

然而，由於計劃增加業務投資，包括對創新產品線中的關鍵資產（例如Mari、Olpasiran和AMG 193）以及其他戰略業務投資（包括在業務各個環節的生成式人工智慧應用案例），我們預計第四季度非GAAP每股收益將低於第三季度。這一周期性變化與歷史趨勢相符。

And in addition, Q4 non-GAAP EPS will begin to include the recognition of interest expense related to the Horizon financing as a non-GAAP expense. Important additional points to consider as you model the remainder of 2023. We now expect other revenue for 2023 to be in the range of $1.2 billion to $1.3 billion versus our prior range of $1.1 billion to $1.3 billion. With the Horizon acquisition, we now anticipate full year non-GAAP operating expense for 2023 to increase from our previous estimate of 3% to approximately 10% versus last year.

此外，第四季度非GAAP每股收益將開始計入與Horizo​​​​n融資相關的利息支出，並將其作為非GAAP費用確認。在2023年剩餘時間建模時，還需考慮以下重要事項。我們現在預計2023年其他收入將在12億美元至13億美元之間，高於先前預期的11億美元至13億美元。由於收購了Horizo​​​​n，我們現在預計2023年全年非GAAP營運費用將從先前估計的3%增加到約10%。

Horizon represents approximately 5 percentage points of this 10% year-over-year increase. We continue to expect the full year 2023 operating margin as a percentage of product sales to be roughly 50%. We continue to expect non-GAAP cost of sales as a percentage of product sales to be between 16% and 17%. We now expect our non-GAAP R&D expenses to increase from our prior guidance of 5% to about 10% year-over-year. Horizon represents approximately 3 percentage points of this 10% year-over-year increase. The additional 2 percentage points are driven by planned increase in our investments in our innovative pipeline, including Mari, Olpasiran and AMG 193. We continue to expect non-GAAP SG&A to be down year-over-year as a percentage of product sales slightly.

Horizo​​n計畫約佔這10%年成長中的5個百分點。我們仍預期2023年全年營業利潤率（佔產品銷售額的百分比）約為50%。我們仍預期非GAAP銷售成本（佔產品銷售額的百分比）將介於16%至17%之間。我們現在預計非GAAP研發費用將從先前5%的預期成長至約10%。 Horizo​​n計畫約佔這10%年成長中的3個百分點。剩餘的2個百分點主要來自我們計劃增加對創新產品線的投資，包括Mari、Olpasiran和AMG 193。我們仍預期非GAAP銷售、管理及行政費用（佔產品銷售額的百分比）將略有下降。

We now expect non-GAAP OI&E expenses to be in the range of $1.4 billion to $1.5 billion, up from our prior guidance of $1.1 billion to $1.2 billion. We expect Q4 OI&E to be about $700 million reflecting interest expense related to the Horizon financing, which will be included in our non-GAAP results effective October 6.

我們現在預計非GAAP營運支出及費用將在14億美元至15億美元之間，高於先前預期的11億美元至12億美元。我們預計第四季度營運支出及費用約為7億美元，其中包括與Horizo​​​​n融資相關的利息支出，該支出將從10月6日起計入我們的非GAAP業績。

And as you begin to model 2024, note that we expect 2024 OI&E to be consistent with this Q4 run rate. This higher interest expense is driven by the $28 billion of debt raised for the Horizon acquisition at a weighted average interest rate of 5.6%. We expect to end 2023 with approximately $65 billion of long-term debt, including the current portion of it and $11 billion of cash and cash equivalents. For the full year, we anticipate a non-GAAP tax rate of 16.5% to 17% down from prior guidance of 17.5% to 18.5%. We expect approximately 540 million shares to be outstanding in Q4. This increase from Q3 is driven by the conversion of unvested Horizon equity awards into Amgen equity awards. Our 2023 capital expenditures are now projected to be approximately $950 million, up from our prior guidance of $925 million.

在您開始建立2024年模型時，請注意，我們預計2024年的營運收入和支出將與第四季度的運行水準保持一致。利息支出增加主要是由於為收購Horizo​​n而籌集的280億美元債務，加權平均利率為5.6%。我們預計到2023年底，長期債務約650億美元，其中包括流動負債部分，以及110億美元的現金及現金等價物。全年非GAAP稅率預計為16.5%至17%，低於先前17.5%至18.5%的預期。我們預計第四季流通股數約為5.4億股。較第三季成長的主要原因是未歸屬的Horizo​​​​n股權獎勵轉換為安進股權獎勵。我們目前預計2023年的資本支出約為9.5億美元，高於先前9.25億美元的預期。

The addition of Horizon's rare disease team further strengthens our confidence in delivering against our long-term growth objectives. We continue to allocate capital to advance innovation at speed and at scale. And I'm incredibly grateful to our now 26,000-plus colleagues for successfully executing our mission of serving patients. This concludes the financial update.

Horizo​​n罕見疾病團隊的加入進一步增強了我們實現長期成長目標的信心。我們將繼續投入資金，以快速、大規模地推動創新。我衷心感謝我們超過26,000名同事，感謝他們成功地履行了我們服務患者的使命。以上是本次財務更新的全部內容。

And now I will ask our operator, Julianne, please open the lines for Q&A and remind our participants of the procedure to ask their questions. Julianne?

現在我請我們的接線生朱莉安娜開通問答環節，並提醒各位參與者提問的流程。朱莉安娜？

(Operator Instructions)

（操作說明）

Our first question comes from Michael Yee from Jefferies.

我們的第一個問題來自傑富瑞集團的麥可葉。

Thanks for all the details around the Horizon transaction. I just wanted to ask a question to David Reese. I mean, David, unless we're hiding under a rock, I guess, obesity is like the biggest thing ever now, and I wanted to understand your commentary and confidence around 133 and the profile around what you think that could be relative to leaders and how 786 would fit into that given such a high bar for other orals?

感謝您提供的關於Horizo​​​​n交易的所有細節。我只想問David Reese一個問題。 David，除非我們與世隔絕，否則我想說，肥胖現在是個大問題。我想了解您對133的看法和信心，以及您認為它相對於領導者而言意味著什麼，考慮到其他口試要求如此之高，786又將如何融入其中？

Yes, sure. As we've discussed before, Mike, with 133, we believe we have a potentially differentiated product based on the mechanism of action. It's a bifunctional to remind everyone that antagonizes GIPR based on genetic evidence largely compiled by us with 2 GLP-1 peptides stapled to the molecule for that mechanism of action.

當然可以。正如我們之前討論過的，Mike，我們相信，基於其作用機制，我們的133產品具有潛在的差異化優勢。需要提醒大家的是，它是一種雙功能藥物，能夠拮抗GIPR，主要基於我們收集的遺傳學證據。在該藥物分子上連接了兩個GLP-1肽，從而發揮其作用機制。

As I noted in the remarks, we've rapidly enrolled the Phase II trial. There are multiple arms to this trial that explore 3 different doses as well as different dosing intervals that I think will give us broad optionality going forward. We were quite pleased with the Phase I data in terms of depth of response, the kinetics of response as well as persistence. And these are the things that we will be looking at in Phase II as we go forward. So it's full steam ahead on this program, and we're looking forward to data from the Phase II trial next year, which will really inform the breadth of the Phase III trial that we're contemplating, which could be quite hard.

正如我在演講中提到的，我們已迅速啟動了二期臨床試驗的受試者招募工作。該試驗設有多個試驗組，探索三種不同的劑量以及不同的給藥間隔，我認為這將為我們未來的研究提供廣泛的選擇。我們對一期臨床試驗的數據非常滿意，包括療效深度、療效動力學、療效持久性。這些正是我們將在二期臨床試驗中重點關注的面向。因此，該計畫正在全力推進，我們期待明年獲得二期臨床試驗的數據，這些數據將為我們正在考慮的三期臨床試驗的開展提供重要的參考依據，而三期臨床試驗的開展可能頗具挑戰性。

In terms of AMG 186 or 786, this is an orthogonal mechanism of action. We're bringing in data and as we've indicated through the first half of next year, so we anticipate presenting those data and determining the path forward. As you note, it's a high bar in this field, and we'd have to see the sort of profile that would give us the confidence to invest broadly in a molecule like that. I would also note, we've got a suite of preclinical molecules, many of them non-incretin based in terms of mechanisms of action that we'll be bringing forward over the next few years. So this is an area where we expect it to be a long-term player.

就AMG 186或786而言，這是一種正交作用機制。我們正在收集數據，正如我們之前提到的，預計明年上半年將公佈這些數據，並確定未來的發展方向。正如您所指出的，該領域的門檻很高，我們需要看到能夠讓我們有信心對這類分子進行廣泛投資的指標。我還想指出，我們擁有一系列臨床前分子，其中許多分子的作用機制並非基於腸促胰島素，我們將在未來幾年內推進這些分子的研究。因此，我們預計該領域將長期發展。

Our next question comes from Yaron Werber from Cowen.

我們的下一個問題來自 Cowen 公司的 Yaron Werber。

Great. Peter, just for you, the $700 million run rate, that was interest expense only, right? That's not including where you're recording sort of the Beijing contribution in the line right above it in terms of other income. And then just secondly, again, on your guidance, you also mentioned 3% to 10% increase year-over-year and you mentioned 5% to 10% going to R&D. The 3% to 10% increase, just remind us what that was because SG&A is expected to be down, right, slightly year-over-year. So I just missed what that was.

好的。彼得，我專門問你一下，7億美元的年化率只是利息支出，對吧？這不包括你在上面那一行提到的其他收入中記錄的北京貢獻。其次，關於你的績效指引，你提到年增3%到10%，研發投入佔5%到10%。 3%到10%的成長率，請你再提醒一下具體是多少，因為銷售、管理及行政費用預計會比去年同期略有下降，對吧？所以我沒聽清楚具體數字。

Right. Thank you, Yaron. The $700 million is everything. So that's the full run rate. And on the -- your question on R&D, as I said in my remarks, we focused our spending on the later clinical and in-market portfolio that was slightly offset by some decreases in early research, but we continue to spend and invest in the business and we'll continue to do that. As you can see, we're fortunate to have a significant number of opportunities in Phase III in the later stages. So that's what we'll stay focused on. We'll continue to differentially invest in the opportunities and innovation, and we're very excited about that.

好的，謝謝你，亞倫。 7億美元就是全部。這就是全部的營運成本。至於你問的研發問題，正如我剛才所說，我們把投入重點放在了後期臨床和已上市產品上，早期研發方面的投入有所減少，但我們會繼續投資於業務，而且會一直這樣做。正如你所看到的，我們很幸運地擁有大量處於後期三期臨床試驗階段的機會。所以，我們會繼續專注於此。我們將繼續對這些機會和創新進行差異化投資，我們對此感到非常興奮。

Our next question comes from Terence Flynn from Morgan Stanley.

下一個問題來自摩根士丹利的特倫斯·弗林。

Great. Maybe a two-parter from me for Peter as well. Peter, again, I know you ran through a lot of numbers there at the end. But in terms of the revenue guidance raise for the year, can you just characterize if that was all coming from the Horizon portfolio or if there was any other contribution from the underlying base business?

好的。或許我也要分兩部分回答彼得的問題。彼得，我知道你最後列舉了很多數據。但關於今年的營收預期上調，你能否具體說明一下，這些成長是否全部來自Horizo​​​​n產品組合，還是基礎業務也有其他貢獻？

And then the second part of the question is just any directional help with how to think about 2024 tax rate, as I know there's a number of moving pieces from some legislation, but then you obviously have the Horizon deal close. So just directionally, can you help us out on 2024 tax rate?

問題的第二部分是關於如何看待2024年稅率的指導，我知道這其中有很多變數，包括一些立法，但顯然Horizo​​n協議也即將達成。所以，能否就2024年的稅率提供一些方向性的指引？

Yes. So on the tax rate, let me start with that 2024 tax rate. We'll guide on that as we always do at the beginning of the year. I would just say, I think you're thinking about the global minimum tax in Pillar 2, and I would just note, there's no consensus or predictability about how that whole OECD framework is going to be implemented. I know different countries are doing different situations. Rest assured, we look at everything optimize our position as appropriate on something like that. So we'll give you guidance on that next year at the beginning of the year. First part of the question?

是的。關於稅率，我先來談談2024年的稅率。我們會像往常一樣在年初提供指導。我想說的是，您可能在考慮第二支柱中的全球最低稅，但我需要指出的是，對於整個經合組織框架將如何實施，目前還沒有共識或可預測性。我知道不同國家的情況各不相同。請放心，我們會密切注意所有情況，並酌情優化我們在這類問題上的立場。因此，我們會在明年年初就此提供指導。問題的第一部分是什麼？

Yes. On revenue, look, we don't really break that down. I would just suggest that we continue to see strength in the business. And we continue to see our in-line portfolio perform very, very well. I would just note we had 7 products with record sales in the quarter. We had Repatha up 31% up in the quarter year-over-year, and we continue to see the hematology/oncology portfolio was up 16%.

是的。關於營收，我們並沒有特別列出。我只想說，我們業務持續保持強勁勢頭。我們的在售產品組合表現依然非常出色。值得一提的是，本季我們有7款產品創下了銷售紀錄。其中，Repatha的銷售額年增了31%，血液腫瘤產品組合的銷售量也成長了16%。

So everything is strong in our base business. We're excited about that base business. It continues to perform really well, and we're very excited to have the rare disease business now. And looking forward to having that as we said, is kind of the fourth stool of our commercial thrust forward. So we're seeing a good strength around the business in different areas, and we'll just continue to get more and more medicines to patients.

因此，我們的基礎業務整體表現強勁。我們對基礎業務充滿信心，它持續保持良好的業績。同時，我們也對現在擁有罕見疾病業務感到非常興奮。正如我們之前所說，這可以說是我們商業策略推進的第四大支柱。因此，我們看到業務在各個領域都展現出強勁的勢頭，我們將繼續努力，為患者提供更多種類的藥物。

I'd note the 11% volume growth is really important underneath that 12% volume growth outside the United States and underneath that, 27% volume growth in JPAC, our fastest-growing region. So that's how we're looking at that. We're pleased with the momentum, and we're pleased to be able to raise the 28.0% to 28.4%.

我想指出，11%的銷售成長非常重要，它低於美國以外地區12%的銷售成長，也低於我們成長最快的地區——亞太地區27%的銷售成長。這就是我們看待這個問題的方式。我們對目前的成長動能感到滿意，也很高興能夠將預期成長率從28.0%提高到28.4%。

Our next question comes from Salveen Richter from Goldman Sachs.

下一個問題來自高盛的薩爾文·里希特。

With regard to the Horizon transaction now that it's closed, could you just walk through the outlook for TEPEZZA and the other assets as we look to 2024 here? You talked about initiatives that you have to expand the patient population in ex U.S. being a growth lever. Just maybe walk us through that and when we might get updated long-term guidance, including Horizon?

關於Horizo​​n交易的完成，能否請您談談TEPEZZA和其他資產在2024年的前景？您提到，公司正在採取措施擴大美國以外地區的患者群體，以此作為成長動力。能否請您詳細介紹一下這些措施，以及我們何時能獲得包括Horizo​​​​n在內的長期業績指引更新？

Yes. Maybe we'll take this in 2 parts, Salveen, it's Bob. Obviously, we're not going to provide '24 guidance here this morning. But we'll see whether we can give you a clear sense of the things that are exciting to us when we look at those products for heading into next year. And just generally, on the question of long-term guidance. As you've heard us say on a number of occasions, we remain confident that we're on track to meet or beat the objectives that we established for 2030. In some ways now, frankly, we're more focused on what we can deliver through 2031 and soon to be 2032 as well.

是的。薩爾文，或許我們可以分成兩個部分來談，我是鮑伯。顯然，我們今天上午不會提供2024年的業績指引。但我們會盡量讓您清楚了解，在展望明年產品時，哪些方面讓我們感到興奮。至於長期業績指引，正如您多次聽到我們所說，我們仍然有信心實現甚至超越我們為2030年設定的目標。坦白說，現在我們更關注的是2031年以及即將到來的2032年能夠達成的成就。

So we reviewed in depth with you the oncology portfolio a couple of weeks ago and that gave you a good sense for the moving pieces through the end of the decade. And we may seek to present a picture of the business in that way now heading into next year so that you can get a more comprehensive deep dive into the different segments of the business that are driving growth. But let's turn to your first question, which is the outlook for Horizon and the initiatives that are underway, in particular with respect to TEPEZZA, KRYSTEXXA, UPLIZNA.

幾週前，我們與您深入探討了腫瘤產品組合，這讓您對未來十年末的業務發展趨勢有了大致了解。展望明年，我們可能會以這種方式向您展示業務概況，以便您更全面、更深入地了解推動業務成長的各個板塊。現在，讓我們回到您的第一個問題，即Horizo​​​​n的前景以及正在進行的各項舉措，特別是關於TEPEZZA、KRYSTEXXA和UPLIZNA的舉措。

So Vikram, why don't you fire away?

維克拉姆，你為什麼不開火呢？

Yes. Thanks for the question. I think as I said in my prepared remarks, we have a lot of positive leading indicators as we look at the business. I start with TEPEZZA, we're continuing to build that U.S. TED market following the FDA's April 2023 label update. And that really helps us get the medicine to TED patients regardless of disease activity or duration. And what we've seen following that label update is that the payers are continuing to update their medical policies and make them more favorable so that more of these patients, more in the low CAS setting or the low clinical activity score setting, can now access TEPEZZA.

是的，謝謝你的提問。正如我在準備好的發言稿中所說，從業務角度來看，我們有許多正面的先行指標。首先是TEPEZZA，在FDA於2023年4月更新標籤後，我們正在繼續拓展美國TED市場。這確實有助於我們讓TED患者無論疾病活動度或病程長短都能獲得藥物。標籤更新後，我們看到支付方正在不斷更新他們的醫療政策，使其更加有利，從而使更多患者，尤其是臨床活動評分（CAS）較低的患者，能夠獲得TEPEZZA。

And I think finally, from an execution standpoint, we see newer prescribers from both ophthalmologists as well as endocrinologists increasing 50% year-over-year in this third quarter. So all of these indicators for TEPEZZA are positive, and we feel good about the execution of the team. And as I said, we have now combined forces with Amgen. And together, we should be able to drive the business in a positive way moving forward.

最後，從執行層面來看，我們看到第三季眼科醫師和內分泌科醫師開立的新處方數量年增了50%。因此，TEPEZZA的所有這些指標都是正面的，我們對團隊的執行力感到滿意。正如我所說，我們現在已經與安進公司強強聯合。我們相信，攜手合作，我們能夠更好地推動業務向前發展。

I think -- talking about -- the story around TEPEZZA also is one of international growth. While we see a lot of positive trends in the U.S., we're pretty excited about what we can do as a combined company for patients outside the U.S. as well. We've talked about Brazil getting approval recently.

我認為，談到TEPEZZA的故事，也離不開其國際化發展。雖然我們在美國看到了許多積極的趨勢，但我們也對合併後的公司能夠為美國以外的患者帶來什麼感到非常興奮。我們之前也提到過，巴西最近獲得了批准。

We've got chronic -- OPTIC-J as our trial in Japan, we've talked about a chronic trial that's enrolling and finally, we're getting ready for other markets, and we hope to bring the medicine to many more markets now as part of the combined company than we were talking about previously. So TEPEZZA both signs very positive in the U.S. as well as globally.

我們已經在日本進行了慢性病臨床試驗——OPTIC-J，我們也討論過一項正在招募患者的慢性病臨床試驗，最後，我們正在為其他市場做準備，我們希望透過合併後的公司，將這種藥物推向比之前更多的市場。因此，TEPEZZA 在美國和全球範圍內都展現出了非常積極的跡象。

And as we've talked about the results for KRYSTEXXA and UPLIZNA, both those medicines performed really, really well. We have immunomodulation with KRYSTEXXA being a major driver since the label update last year. That has continued to drive uptake since that time. We see that continuing into the future. And with UPLIZNA, it's the fastest-growing biologic in neuromyelitis optica spectrum disorder, or NMOSD, and we see that momentum continue both in the U.S. as well as outside the U.S. So I think when I look at the overall portfolio, we have -- we're operating from a position of strength, and now we can expand that even further with the combination with Amgen.

正如我們之前討論的KRYSTEXXA和UPLIZNA的療效，這兩種藥物的表現都非常出色。 KRYSTEXXA的免疫調節作用自去年標籤更新以來一直是推動其市場成長的主要動力。此後，免疫調節作用持續推動了KRYSTEXXA的市場成長，我們預期這一趨勢將持續下去。 UPLIZNA是視神經脊髓炎譜系障礙（NMOSD）領域成長最快的生物製劑，我們看到其在美國及其他地區的成長勢頭依然強勁。因此，我認為，縱觀我們整體的產品組合，我們擁有強大的實力，而與安進的合作將進一步擴大我們的市場優勢。

Our next question comes from Jay Olson from Oppenheimer.

我們的下一個問題來自奧本海默公司的傑伊·奧爾森。

Congrats on all the progress on so many fronts. Could you talk about your investments in AI technology and how that may influence your drug discovery and development over the next 5 to 10 years?

祝賀你們在許多方面所取得的進展。能否談談你們在人工智慧技術方面的投資，以及這些投資在未來5到10年內將如何影響你們的藥物發現和發展？

Sure. I'll ask Dave Reese to address that, Jay.

當然。我會請戴夫·里斯處理這件事，傑伊。

Yes. Thanks, Jay. This is an area where we're very excited. I'd like to characterize it as a hinge moment where we're seeing the coming together or the unification of technology and biotechnology. I really think this is going to affect over time a qualitative change in how we do drug discovery and drug development.

是的，謝謝傑伊。我們對這個領域非常興奮。我想把它看作是一個關鍵時刻，我們正見證著科技和生物技術的融合與統一。我真的認為，隨著時間的推移，這將從根本上改變我們進行藥物發現和研發的方式。

So everything from protein structure prediction, protein-protein interaction prediction at the molecular level to multiomic analysis on extraordinarily large data sets, which is only tractable through AI or machine learning, dense clinical trials data and then real-world evidence in real-world data. When you look across that spectrum, I believe we probably have the largest data sets in the industry.

因此，從蛋白質結構預測、分子層面的蛋白質-蛋白質相互作用預測，到對極其龐大的數據集進行多組學分析（這只有透過人工智慧或機器學習才能處理），再到密集的臨床試驗數據以及真實世界數據中的真實世界證據，我們涵蓋了所有方面。縱觀所有這些領域，我相信我們擁有業內最大的數據集。

And so we are putting the tools in place and the foundational model to really mine those data for deeper insights in the biology and then all the way out into the market. We'll talk about this more over time, but this is going to be an area of investment. And it can be overhyped. It's not a panacea, but it is absolutely going to be the most powerful tool we have seen in a long, long time.

因此，我們正在部署工具並建立基礎模型，以便真正挖掘這些數據，從而更深入地了解生物學，並將其推向市場。我們會隨著時間的推移對此進行更詳細的討論，但這將會是一個值得投資的領域。當然，它也可能被過度炒作。它並非萬能靈藥，但它絕對會是我們很久以來見過的最強大的工具。

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。

Dave, I have a 2-part question on AMG 786, the oral for obesity. First, I noticed you guys dropped a cohort in your SAD portion of the trial. Is that because you ran into MTB? And then also, I noticed the exclusion criteria around suicide ideation were intensified, and I can't tell if we could be reading into that or not. Would love to get any color.

Dave，關於AMG 786（一種治療肥胖的口服藥物），我有兩個問題。首先，我注意到你們在SAD（社交焦慮症）測驗部分剔除了一組受試者。這是因為你們遇到了MTB（多發性骨髓瘤）嗎？其次，我也注意到你們加強了對自殺意念的排除標準，我不知道這是否與此有關。希望能得到一些解答。

Yes. Thanks, Umer. On the latter, I wouldn't overthink that at all. I don't think there's anything there. In terms of the dosing that we do, this is always adjusted as we move through Phase I trials as indicated, we're bringing in the data now. We're taking a look at that and the constellation of clinical data, updated preclinical data. And I think we'll have that all together as we go into next year, and that will determine the potential path forward for AMG 786. And just to remind everyone, this is a target that is not an incretin-based target.

是的，謝謝，Umer。關於後者，我完全不認為需要過度思考。我覺得沒什麼問題。至於劑量方面，我們會根據I期臨床試驗的進展進行調整，目前我們正在收集相關數據。我們會綜合考慮這些數據以及臨床數據和更新的臨床前數據。我認為到明年，我們將掌握所有信息，這將決定AMG 786的未來發展方向。最後提醒大家，AMG 786並非基於腸促胰素的標靶。

Our next question comes from Robyn Karnauskas from Truist Securities.

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

I just have a follow-up to Salveen's question actually. So TEZSPIRE has not gotten a lot of market share. There's so much room to grow in the TED space. Can you walk me through like how Amgen can actually help grow that business because I'm confused by whether it's the hearing loss or reimbursement or what are really the levers who actually grow that company -- grow that business, it's, TEPEZZA, sorry, TEPEZZA. But I think that there's a lot of room to grow and given your strength, you could probably make that work. So how do you intend to do that?

我其實想就Salveen的問題再補充一點。 TEZSPIRE的市佔率並不大。在TED領域還有很大的成長空間。您能否詳細解釋一下安進如何才能幫助TEZSPIRE發展這項業務？因為我不太清楚，究竟是聽損問題、健保報銷，還是其他因素真正推動了TEZSPIRE的發展──是TEZSPIRE，抱歉，是TEZSPIRE。但我認為TEZSPIRE的發展空間很大，以你們的實力，應該能夠成功。那麼，你們打算如何實現呢？

Okay. Thank you, Robyn. So I think it's a 2-part question there in TEPEZZA. We may tackle in 2 parts, the combination for Vikram and Murdo. So go ahead. Vikram, why don't you start?

好的。謝謝你，Robyn。所以我覺得TEPEZZA那邊的問題分兩部分。我們可以分成兩個部分來討論Vikram和Murdo的組合。那麼，Vikram，你先來吧？

Yes. Thanks for the question. I'd like to -- earlier, the -- I think one of the areas that has -- something that happened this year was the FDA update. Now when the label updates to patients that are treated regardless of disease activity or duration, many of these patients, as I'll say more of these patients are being treated by prescribers such as endocrinologists and ophthalmologists. And that's where the team has been focused on working through making sure that our education programs available to these physicians so that we can widen our prescriber base from the original set of prescribers that started treating patients at launch. So it's really important to understand that expanding the prescriber base is a critical driver for that success going forward.

是的，謝謝你的提問。我想說的是——早些時候，我認為今年發生的一件事是FDA的更新。現在，標籤更新後適用於所有接受治療的患者，無論疾病活動度或病程長短。正如我所說，越來越多的這類患者是由內分泌科醫生和眼科醫生等處方醫生開立的處方。因此，我們的團隊一直致力於確保這些醫生能夠獲得我們的教育項目，以便我們能夠擴大處方醫生群體，使其不再局限於產品上市之初就開始治療患者的醫生。所以，我們必須明白，擴大處方醫生群體是未來成功的關鍵驅動因素。

And as we've seen, new prescribers have increased 50% year-over-year. As we continue to work through these -- this low CAS or low clinical activity patients, we also have to remember that when they are prescribed the medicine, payers need to open up access to the medicine. So our market access team has been working pretty diligently to make sure that payers continue to update their medical policies. And what we have seen is more than 30% of U.S. covered lives are now eligible for patients that can access TEPEZZA with more open or more favorable policies. This has to continue. And both of these are areas that we will continue to work on as we go into early next year and beyond.

正如我們所見，新處方醫生的數量比去年同期增加了50%。在我們繼續努力解決這些低臨床活動度（CAS）患者的問題時，我們也必須記住，當他們獲得處方時，支付方需要開放藥物取得途徑。因此，我們的市場准入團隊一直在努力確保支付方持續更新其醫療政策。我們看到，超過30%的美國投保人員現在有資格獲得TEPEZZA，因為支付方的保單更加開放或優惠。這種情況必須繼續維持。這兩個領域都是我們明年年初及以後將繼續努力的方向。

And maybe I'll turn it over to Murdo to add his comments as well.

或許我還會把話題交給默多，讓他也發表一下看法。

Yes. Thanks, Vikram. Robyn, I would add much the same way when we acquired ChemoCentryx and TAVNEOS, we realized that there was a low level of awareness of TAVNEOS. What we did there was we added a reminder messaging to some of our broader rheumatology covered sales forces to increase awareness of the data associated with TAVNEOS and ANCA-associated vasculitis patients, we've seen a corresponding increase in utilization, of course, driven by awareness of that product.

是的，謝謝Vikram。 Robyn，我想補充一點，我們收購ChemoCentryx和TAVNEOS時也遇到了類似的情況。當時我們發現TAVNEOS的知名度很低。我們採取的措施是，在負責風濕病業務的銷售團隊中增加提醒訊息，以提高他們對TAVNEOS和ANCA相關性血管炎患者相關數據的認識。當然，隨著人們對該產品的認知度提高，TAVNEOS的使用率也相應提高了。

So the core team is still promoting the attributes of the product and educating physicians, but there's a broader group of field personnel building general awareness of that product. What I think, Vikram and I are talking about is the Amgen teams that cover endocrinologists who are involved in the diagnosing and treatment of thyroid eye disease would be an ideal opportunity for us to broaden awareness amongst that community of endocrinologists who are diagnosing and treating thyroid eye disease today to augment the great work that is happening with the rare disease teams under Vikram's leadership.

因此，核心團隊仍在推廣產品特性並進行醫生培訓，但同時也有一支更廣泛的現場人員隊伍在提升公眾對該產品的整體認知度。我認為，我和Vikram討論的是，安進公司負責內分泌科醫生（尤其是那些參與甲狀腺眼病診斷和治療的醫生）的團隊，對於我們來說是一個絕佳的機會，可以藉此機會提高目前從事甲狀腺眼病診斷和治療的內分泌科醫生群體對該產品認知度的提升，從而進一步加強Vikram領導的罕見病團隊正在開展的罕見卓卓病團隊正在開展的罕見的工作。

So there's a number of things like that where we can scale and speed up the building of awareness, for example, of the new data that Vikram was just describing and the broadening of the label language.

因此，有很多類似的事情我們可以擴大規模並加快人們的認識，例如，Vikram 剛才描述的新數據以及標籤語言的擴展。

Vikram also mentioned the international expansion. The original plan was quite ambitious for Horizon. We've actually increased the number of markets that we intend to file and launch in a shorter period of time. So that would be an additional opportunity for growth given the strength of the 2 companies now combined.

Vikram也提到了國際擴張。 Horizo​​n最初的計劃相當雄心勃勃。實際上，我們已經增加了計劃在更短時間內提交申請並推出產品的市場數量。鑑於兩家公司合併後的實力，這將帶來額外的成長機會。

Might just add also, Robyn, that in terms of the time course of events here, I think now that we reflect back on a year of ownership of ChemoCentryx, we can really start to see the benefit of what Murdo just described kicking in, in the last few weeks and months. So it takes a little bit of a while, but I think our confidence is that over that period of time, we've been able to find ways that we can add distinctive value to that product. And we're hoping the similar thing will happen with respect to the new rare disease molecules that we brought on board. So it's not like walk-ins, flip a light switch and suddenly things are performing on a different track, but rather come in, work together, identify the ways in which we can be additive in the marketplace. And I'm hopeful that we'll see during the course of '24, the momentum build for the combined organization on these products.

羅賓，我還要補充一點，就目前的情況來看，回顧我們收購ChemoCentryx一年來，我們確實開始看到默多剛才描述的好處在過去幾周和幾個月裡逐漸顯現。這需要一些時間，但我相信，在這段時間裡，我們已經找到了為該產品增添獨特價值的方法。我們希望類似的情況也能發生在我們引進的新型罕見疾病分子藥物上。這並非一蹴而就，也不是一蹴而就，而是需要我們共同努力，找到在市場上創造價值的方式。我希望在2024年，我們能夠看到合併後的公司在這些產品上取得更大的發展勢頭。

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。

Yes. And so my question is on oral obesity development. Regarding Phase I candidate 786, management has consistently emphasized that it also has a suite of oral preclinical products. And so should we take away that we should be viewing 786 as more of a wildcard rather than something that Amgen has conviction in at this point? And when do you expect to be able to start Phase I for another oral preclinical candidate might that happen in '24 or not until '25?

是的。所以我的問題是關於口服肥胖症藥物的研發。關於I期候選藥物786，管理階層一直強調公司還有一系列口服臨床前產品。那我們是否應該認為786更像是未知數，而不是安進目前非常看好的藥物？您預計何時能夠啟動另一個口服臨床前候選藥物的I期臨床試驗？是在2024年還是要等到2025年？

And then separately, just -- I wanted to squeeze in a quick financial question. Do you expect Horizon product channel inventory work down in the fourth quarter to significantly constrain reported net Horizon sales in the fourth quarter?

另外，我還想快速問一個財務方面的問題。您預計第四季度Horizo​​​​n產品通路庫存的減少是否會顯著限制第四季度Horizo​​​​n的淨銷售額？

Yes. Thanks, David. Dave Reese, I'll start and then turn things over to Murdo and Vikram. In terms of oral obesity molecule, 786, as I've said, it has a novel mechanism of action. It's a Phase I molecule. So you should view it as a Phase I molecule and we're bringing in -- as the data I said, and we'll take a look at that as we get into the new year and make a determination on a potential path forward for that molecule. I wouldn't view it as anything more or less than a Phase I asset with a novel mechanism of action. In terms of additional molecules and when we might file INDs and launch first-in-human trials, we'll give guidance as that portfolio advances over time.

是的。謝謝，David。 Dave Reese，我先開始，然後把麥克風交給Murdo和Vikram。關於口服減肥藥786，如我之前所說，它具有一種全新的作用機制。它目前處於I期臨床試驗階段。所以，你應該把它看作是一個I期臨床試驗階段的藥物，正如我剛才提到的，我們正在收集數據，並在新的一年裡仔細研究這些數據，以確定該藥物的潛在發展方向。我認為它就是一個具有全新作用機制的I期臨床試驗藥物，僅此而已。至於其他藥物，以及我們何時可能提交新藥臨床試驗申請（IND）並啟動首次人體試驗，我們會隨著藥物組合的進展提供指導。

Again, many of those molecules are targets that we emanated from deCODE Genetics, our colleagues in Iceland, and I'll provide further information as we get ready to move towards the clinic. But this is playing the long game. If you step back, this field is in its infancy. We are just beginning to understand the complex metabolic arrangements that occur with obesity and there are clearly different forms of obesity. There's a lot of work to do. And as I've indicated, our intent here is to play the long game, given that this is one of the major public health challenges of the 21st century.

再次強調，這些分子中的許多目標都來自我們在冰島的同事 deCODE Genetics，隨著我們準備進入臨床試驗階段，我會提供更多資訊。但這需要長期投入。從長遠來看，這個領域還處於起步階段。我們才剛開始了解肥胖相關的複雜代謝機制，而肥胖顯然有不同的類型。還有很多工作要做。正如我之前提到的，鑑於這是21世紀主要的公共衛生挑戰之一，我們的目標是著眼長遠。

So let me now hand it over to Vikram and Murdo for additional commentary on your second question.

現在，我把這個問題交給 Vikram 和 Murdo，請他們就你的第二個問題作進一步評論。

Yes, David, I just want to make sure that I heard your question right, it was about inventory and product wind down. Look, I don't think we're going to comment on that specific aspect. I think the -- our team remains focused on driving demand and working with physicians to educate them and expanding the use of TEPEZZA for appropriate patients. And that's where we're really focused to as our primary driver of net sales growth.

是的，David，我只是想確認我是否理解了你的問題，是關於庫存和產品下線的問題。嗯，我們目前不打算就此發表評論。我們的團隊仍專注於推動市場需求，與醫生合作，為他們提供相關教育，並擴大TEPEZZA在合適患者中的應用。這才是我們真正關注的重點，也是我們實現淨銷售成長的主要動力。

Our next question comes from Chris Raymond from Piper Sandler.

我們的下一個問題來自Piper Sandler公司的Chris Raymond。

I just -- maybe a commercial question on your dermatology strategy. And specifically on Otezla, just on the dynamic that you guys talked about with free competitor drug. Presumably, that's SOTYKTU scenario. I think I heard you guys you've been calling this issue out for some time, but also with the investment that you're making in the dermatology sales force, I think I heard you say today you're increasing that sales force sort of 20% or so. Is the implication that once the competitor free drug program runs its course that Otezla volume should increase? Or what's your sense of what happens to volume? And maybe I'll ask it another way. If that volume increase doesn't materialize, do you need additional derm portfolio offerings to support that added effort?

我只是想問一個關於你們皮膚科策略的商業問題。特別是關於Otezla，關於你們之前提到的免費競爭藥物的動態。我猜你們指的是SOTYKTU方案。我聽說你們已經關注這個問題一段時間了，而且你們也在加大對皮膚科銷售團隊的投入，我記得今天你們說過要將銷售團隊規模擴大20%左右。這是否意味著，一旦免費競爭藥物計畫結束，Otezla的銷售就會成長？或者你們對銷量會如何改變有什麼看法？我換個方式問。如果銷售量沒有成長，你們是否需要增加皮膚科產品組合來支持這部分新增的投入？

Thanks for the question, Chris, it's Murdo. So let's just recapitulate what's happening in this market. At the beginning of the year, you had a number of new launches, not just SOTYKTU with novel topicals coming into the market as well as a novel oral and every one of those products had very generous free drug programs. And that had 2 effects on Otezla. There were topical patients who would have normally moved to their first systemic option who tried the new topical treatments on a free drug basis. And at the same time, there was a launch of a new oral that had a very generous free drug program.

謝謝你的提問，克里斯，我是默多。我們先來回顧一下目前市場的狀況。年初的時候，有許多新產品上市，不僅是SOTYKTU，還有新型外用製劑和新型口服製劑，而且所有這些產品都有非常慷慨的免費用藥計畫。這對Otezla產生了兩方面的影響。一方面，一些原本會轉而使用全身性治療方案的外用患者，因為有了免費用藥，得以嘗試新的外用療法。另一方面，一款新的口服製劑也推出了非常慷慨的免費用藥計畫。

And so Otezla, which sources the majority of its growth from topical patients first systemic, in other words, biologic-naive patients, Otezla got squeezed in the first and second quarter on the basis of those new programs coming into the market.

因此，Otezla 的成長主要來自局部用藥患者，而非全身用藥患者（換句話說，是生物製劑初治患者），在第一季度和第二季度，由於市場上新項目的湧入，Otezla 的業績受到了擠壓。

What we've seen since those 2 events in the market is that the novel topicals have flattened out in their growth and have pulled back to some extent on their free drug offering.

自從這兩起市場事件以來，我們看到新型外用藥物的成長已經趨於平緩，並且在一定程度上減少了免費藥物的供應。

The other oral therapy, SOTYKTU continues to provide free drug. And so it continues to have some effect on Otezla. What we think will happen and we're already seeing the very early signals of this is that we will continue to source our new growth from the topical patients -- bio-naive patients, given that Otezla is the ideal for a systemic agent. We have established ourselves with really strong access in the market. So we don't need to provide free drug programs to the extent that everybody else is. And then as the contracting cycle for 2024 matures and we see what the actual access is for some of the other competitors in the market, including the new oral, we should be able to give better guidance on our growth prospects for the future. But we almost certainly expect the impact of the free goods program to continue to reduce and that will help us grow Otezla.

另一種口服療法SOTYKTU仍在繼續提供免費藥物，因此它對Otezla的銷售仍有一定影響。我們認為，並且我們已經看到了一些早期跡象，我們將繼續從局部用藥患者（即生物製劑初治患者）那裡獲得新的增長，因為Otezla是理想的全身用藥。我們在市場上已經建立了非常穩固的准入管道，因此我們不需要像其他公司那樣提供大量的免費藥物項目。隨著2024年合約週期的完成，當我們了解市場上其他競爭對手（包括新型口服藥物）的實際准入情況後，我們應該能夠更好地預測未來的成長前景。但我們幾乎可以肯定，免費藥物項目的影響將繼續減弱，這將有助於Otezla的成長。

The investments we've made are really just kicking in this quarter. So the expansion in the field force and your number was right by 20%. The derm team was just deployed at the beginning of Q4. So they are only in field as of a few weeks. So that impact is not in the historical performance of the brand and our direct-to-consumer spend has been increased for the fourth quarter as well. So we'll be able to tell you more as we go forward. But we feel, given the very large number of patients here who continue to persist on topicals when they really are better candidates for a systemic agent, will convert to Otezla as we build into that market.

我們先前的投資在本季才真正開始發揮作用。銷售團隊的擴張，正如您所說，成長了20%。皮膚科團隊是第四季初才部署到位的，所以他們才上線幾週時間。因此，這方面的影響尚未體現在品牌的歷史表現上。此外，我們第四季的直接面向消費者的支出也有所增加。隨著我們不斷推進，我們會提供更多資訊。但我們相信，鑑於目前有大量患者明明更適合使用全身性藥物卻仍然堅持使用外用藥，隨著我們拓展市場，他們最終會轉而使用Otezla。

And just a reminder, we're the only product in the market that has a broad label regardless of severity of psoriasis. So we're optimistic and we're enthusiastic, and that's why we've made these investments, and we'll continue to look to add to our dermatology portfolio as we go forward.

再次提醒大家，我們是市面上唯一一款無論乾癬嚴重程度如何都適用的廣譜產品。因此，我們充滿信心和熱情，這也是我們進行這些投資的原因，未來我們將繼續拓展我們的皮膚科產品組合。

Our next question comes from Mohit Bansal from Wells Fargo.

下一個問題來自富國銀行的莫希特·班薩爾。

So maybe 1 question on sequential growth. If I look at second quarter from third quarter, it seems like pretty much every product, even including (inaudible) accounts for the government budget seems to be down. I know that you warned about this in the second quarter call regarding Medicare donut hole, but can you talk a little bit about the dynamics there? And how should we be thinking about it going forward?

所以，關於環比成長，我可能有一個問題。如果我比較第二季和第三季度，似乎幾乎所有產品，甚至包括（聽不清楚）政府預算帳戶，都出現了下滑。我知道您在第二季財報電話會議上就醫療保險缺口（Medicare donut hole）的問題發出過警告，但您能否詳細談談其中的動態？以及我們應該如何看待這個問題？

Yes. Mohit, I don't think every product is down. I think we had a number of products posting pretty significant double-digit growth in the quarter, and those are products that we continue to expect long-term growth from products like Repatha, EVENITY, Prolia, our heme/onc portfolio, BLINCYTO in particular.

是的，莫希特，我認為並非所有產品都下滑了。我們有許多產品在本季度實現了兩位數的顯著成長，我們仍然預期這些產品，例如瑞百安（Repatha）、依維寧（EVENITY）、普羅利亞（Prolia）、我們的血液/腫瘤產品組合，特別是布林西托（BLINCYTO），將持續保持長期成長。

So we're seeing some strength in our priority growth brands that we expect to continue to drive. What we did have in the quarter were a number of adjustments from prior period on net sales. So there was 1 particular adjustment on LUMAKRAS which was based on a year-over-year change in the negotiations that we have on reimbursement. So in France, for example, we have an early temporary access program, an ATU program. Since 2021, LUMAKRAS has been available in France and we took a $22 million accrual in the quarter for those sales on the basis of price negotiations we're having in France.

因此，我們看到重點成長品牌表現強勁，預計這種勢頭將持續保持。本季我們對淨銷售額進行了一些調整，與上期相比有所變動。其中一個調整是關於LUMAKRAS的，這是由於我們在報銷談判中與去年同期相比發生了變化。例如，在法國，我們有一個早期臨時准入計劃（ATU）。自2021年以來，LUMAKRAS已在法國上市，本季我們根據在法國的價格談判結果，為這些銷售額提列了2,200萬美元的應計費用。

So we had a number of events like that related to price in the quarter. And as you mentioned, we are entering the donut hole for some of our products. So overall, I think unit volume growth is very strong, a few price effects on select products in the portfolio and a little bit of donut hole impact.

所以本季我們遇到了一些與價格相關的類似事件。正如您所提到的，我們部分產品正進入價格區間波動期。因此，整體而言，我認為銷售成長非常強勁，只是部分產品受到價格波動的影響，以及價格區間波動帶來的影響較小。

Our next question comes from Gregory Renza from RBC Capital Markets.

下一個問題來自加拿大皇家銀行資本市場的格雷戈里·倫扎。

Congrats on the progress. Bob, just circling back to the obesity market again and as you and the team focus on really being best -- being first and/or best-in-class across markets. I'm just curious how you and the team view and anticipate how different the obesity market could look and how you see the unmet need morphing by the time -- a program from Amgen is ready for prime time? But would there be a need to look not just internally but externally to accelerate those efforts, especially if things are evolving so quickly? Congrats on the progress.

恭喜取得的進展。鮑勃，我再次回到肥胖症市場這個主題，你和你的團隊致力於做到最好——在各個市場都做到領先或同類最佳。我很好奇你和你的團隊如何看待和預測肥胖症市場未來的變化，以及當安進的某個專案準備就緒時，未被滿足的需求會發生怎樣的轉變？但是否需要從內部和外部尋求資源來加快這些努力，尤其是在情況如此快速變化的情況下？恭喜取得的進展。

We're very excited about what we see so far emerging from our early work in obesity. I think over time, you got a sense of this from Dave Reese, this is likely to be a heterogeneous disease. There are probably going to be a number of different ways to have to go at it.

我們對目前在肥胖症早期研究方面所取得的成果感到非常興奮。我認為，正如戴夫·里斯所說，隨著時間的推移，肥胖症很可能是一種異質性疾病。或許需要採取多種不同的治療方法。

But what encourages us right now is what we think of as an emerging differentiated profile for our approach versus the competition.

但目前讓我們感到鼓舞的是，我們認為我們的方法與競爭對手相比，正在形成差異化優勢。

And maybe Murdo, do you want to just jump in and remind Gregory about the basis of differentiation that we see so far in our data from the competition and why we think that gives us a good foothold for entering the market?

或許默多，你想插一句，提醒格雷戈里，我們目前從競爭對手的數據中看到的差異化基礎是什麼，以及為什麼我們認為這能讓我們更好地進入市場？

Yes. Thanks, Bob. I like the way the question was framed that sometimes gets framed as what are you going to do with these entrenched products in the market. And I'd just like (inaudible) people have (inaudible) the market is and how much more is left to unfold. What we're seeing in the early days is we're seeing a lot of patients trying these products losing weight, but then not persisting with their treatment and regaining weight. So we think that there is an opportunity in the market long term for a product that can bring about very strong weight loss, both rapid and sustained over time with convenient dosing.

是的，謝謝，鮑伯。我喜歡你提出的問題方式，這個問題有時會被問到「你們打算如何處理市場上這些根深蒂固的產品？」。我只想（聽不清楚）人們（聽不清楚）市場現況如何，以及還有多少發展空間。我們目前觀察到的情況是，許多患者嘗試這些產品後體重減輕了，但之後沒有堅持治療，體重又反彈了。因此，我們認為，從長遠來看，市場上存在著一種機會，需要一種能夠快速且長期持續地有效減肥，並且服用方便的產品。

And I think that, that's where 133 or Maridebart cafraglutide really has an opportunity to differentiate itself from what is available in the market today. We've seen the durability of that product between doses. We think based on the Phase II and the number of different dosing cohorts we have being explored in that trial, we'll be able to find the right balance of the efficacy and the ability based on convenient dosing to sustain that weight loss over time. And of course, the goal here is not just to lose weight, but to improve a number of sequelae or outcomes from people who carry extra weight over the course of their life.

我認為，133 或 Maridebart 卡夫魯肽的真正優勢在於它能夠與目前市場上的其他產品區分開來。我們已經觀察到該產品在兩次給藥之間療效的持久性。基於 II 期臨床試驗以及我們在試驗中探索的多種不同給藥方案，我們認為能夠找到療效和便捷給藥方案之間的最佳平衡點，從而長期維持減重效果。當然，我們的目標不僅僅是減重，而是改善長期超重人群的一系列後遺症或不良後果。

And that's what we're starting to see with others reading out in event trials. We'll see more data as medical congresses pass this next few months. But our hope is to bring about real improvement in outcomes with a highly efficacious and highly convenient product like 133.

我們從其他機構公佈的臨床試驗數據也開始看到類似情況。未來幾個月，隨著醫學大會的召開，我們將看到更多數據。但我們希望透過像133這樣高效、方便的產品，真正改善患者的治療效果。

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

下一個問題來自美國銀行的傑夫‧米查姆。

It's been a long time coming for Repatha inflection. Are you guys finally hitting a commercial tipping point with payers? Or do you think there is an increasing interest among cardiologists? I guess, I wasn't sure how the current market is and looking forward, how about the impact? How do you guys see it from a couple of the ongoing Phase IIIs and forth?

Repatha的轉機可謂姍姍來遲。你們是否終於在支付方那裡達到了商業轉折點？或者你們認為心臟科醫生對它的興趣正在不斷增長？我不太清楚目前的市場狀況，展望未來，它的影響如何？你們如何看待正在進行的幾項III期臨床試驗？

Thanks for the question, Geoff. Yes, it's been a bit of a journey and the COVID pandemic didn't help us in our efforts to educate and convince cardiologists that they needed to do more to be more aggressive in treating their patients, LDL cholesterol. I do think we've reached a tipping point in cardiology, and I do think we've reached a tipping point with payers. We now have over 90% commercial lives covered.

謝謝你的提問，傑夫。是的，這確實是一段漫長的歷程，而新冠疫情更是雪上加霜，阻礙了我們教育和說服心臟病專家們採取更積極的措施來治療患者的低密度脂蛋白膽固醇（LDL-C）。我認為我們在心臟病學領域已經達到了一個轉折點，在支付方方面面也達到了一個轉折點。現在，我們已經涵蓋了超過90%的商業人壽保險。

We anticipate being able to continue to progress our Medicare Part D coverage and we're seeing the PCSK9 category driven primarily by our 80% share of that category, really, really starting to move now. Our new patient volume growth is good, not just in the U.S. but around the world. We are now seeing more and more primary care physicians using PCSK9s in combination with other drugs to more aggressively lower LDL in high-risk ASCVD patients.

我們預計能夠繼續推進Medicare Part D的覆蓋範圍，並且我們看到PCSK9抑制劑類藥物的市場成長勢頭強勁，這主要得益於我們在該類藥物80%的市場份額。我們的新患者數量成長良好，不僅在美國，而且在全球範圍內都是如此。我們現在看到越來越多的初級保健醫生將PCSK9抑制劑與其他藥物合併使用，以更積極地降低高風險ASCVD患者的LDL膽固醇水平。

So the phases are pretty clear. Payer coverage established affordability for patients, established cardiologists now prescribing with frequency and now moving into primary care, and we'll be adding direct-to-consumer campaign investment to that mix. So yes, I think we've reached a tipping point on Repatha, Geoff, and I'm bullish on what we can do to further expand that product, both from a volume and net sales perspective.

所以各個階段都非常清晰。健保覆蓋確保了病患的用藥負擔能力，心臟科醫師也開始頻繁地開立這種藥物，並逐步推廣到基層醫療機構。此外，我們還將增加面向消費者的直接行銷活動投入。所以，是的，我認為Repatha已經達到了一個關鍵的轉折點，Geoff，我對我們能夠進一步擴大該產品的銷售和淨銷售額都充滿信心。

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 a question on longer-term margins. I guess post Horizon and I guess, with the ramp of your pipeline, including some potentially very large obesity studies over time. I guess just directly, how should we be thinking about margins from here? I guess, is this kind of 50% or slightly above 50% range, a reasonable target for the company or just any considerations we should keep in mind as we kind of balance, I guess, Horizon versus investment?

關於長期利潤率，我有個問題。我想問的是，在Horizo​​​​n計畫之後，隨著貴公司研發管線的逐步推進，包括一些未來可能非常大規模的肥胖症研究，我們該如何看待未來的利潤率？ 50%或略高於50%的利潤率目標對公司來說是否合理？或者說，在權衡Horizo​​​​n計畫和投資時，我們還應該考慮哪些其他因素？

Well, we're not going to give updated margin guidance on this call, Chris. But I think we've been pretty clear about what the trail should look like. We're focused on remaining a leading efficient player in our industry. We've been able to achieve leading operating margins over time. There's nothing that we see in the Horizon business specifically that would need us to conclude differently from that.

克里斯，這次電話會議上我們不會提供最新的利潤率指引。但我認為我們已經非常明確地闡述了未來的發展方向。我們專注於保持業界領先的效率地位。我們一直以來都實現了領先的營業利潤率。就Horizo​​​​n業務而言，我們沒有看到任何需要我們改變這一結論的情況。

So we expect that at a full run rate capitalizing on our in-place infrastructure internationally and manufacturing and process development that the margins of that business will be attractive in our hands. And the reference that Peter made to R&D spend earlier, obviously, to the extent that we get into a number of Phase III trials in the middle years here of the decade for Lp(a) and for obesity products. That may have an effect on overall margins, but we'll have plenty of time to talk about that in advance so that nobody is surprised that the margins start moving around. So again, we've demonstrated a pretty consistent ability to manage the cost structure of the business, and that's something that we're determined to maintain.

因此，我們預計，在充分利用我們現有的國際基礎設施、生產製造和製程開發能力的基礎上，全面投產後，該業務的利潤率將非常可觀。正如Peter先前提到的研發投入，顯然，如果我們在本世紀中期開展多項Lp(a)和肥胖症產品的III期臨床試驗，可能會對整體利潤率產生影響。但我們會事先充分討論這些問題，以免利潤率出現波動時造成任何意外。再次強調，我們已經展現出相當穩定的成本結構管理能力，我們也決心繼續保持這項優勢。

Our next question comes from Evan Seigerman from BMO.

我們的下一個問題來自BMO的Evan Seigerman。

So the growth in prospect is pretty impressive. Just wondering how to mention $1 billion run rate compares with your expectations going into the deal? And then taking a step back, we saw on the JAMA article that the use of type 2 diabetes meds for gout. How are you seeing this in the broader gout space? Is this something we should be concerned about when it comes to KRYSTEXXA?

所以，成長前景確實令人印象深刻。我只是想知道，如何才能更好地表達10億美元的年化收入與您當初達成交易時的預期相比如何？另外，我們之前在JAMA的文章中看到，2型糖尿病藥物被用於治療痛風。您如何看待這在更廣泛的痛風治療領域中的作用？這是否會影響KRYSTEXXA的療效？

Maybe we'll take this in 2 parts. First, with respect to KRYSTEXXA, I'd say KRYSTEXXA is performing very well, and we believed it would. Again, we think there's a tremendously large unmet medical need here and that KRYSTEXXA with methotrexate is serving the marketplace well. So we're looking forward to working with our colleagues on it. And overall, I'd say that the business is proceeding as we thought it would to this point. And the things that we were -- that we thought were important to have in hand like chronic indication for TEPEZZA, like international data sets that were made available with the OPTIC-J trial like the progress we've made in Brazil et cetera, those were things that we wanted to have in hand and now do.

或許我們可以分成兩部分來談談。首先，關於KRYSTEXXA，我認為它的表現非常出色，正如我們預期的那樣。我們再次強調，我們認為目前存在巨大的未滿足醫療需求，而KRYSTEXXA聯合甲氨蝶呤能夠很好地滿足市場需求。因此，我們期待與同事們繼續合作。總的來說，我認為到目前為止，業務進展符合我們的預期。我們先前認為重要的訊息，例如TEPEZZA的慢性病適應症、OPTIC-J試驗提供的國際數據集、我們在巴西取得的進展等等，這些都是我們之前希望掌握的信息，現在也都已掌握。

And again, UPLIZNA also performing very much in line as we expected it would. So we see 3 growth opportunities there and we see ways for the Amgen-based business to add value to what Vikram will be running now in our rare business area. And then with respect to the question on diabetes, I'll ask Dave.

此外，UPLIZNA 的表現也完全符合我們的預期。因此，我們看到了三個成長機會，也看到了安進的業務如何為我們目前在罕見疾病業務領域（Vikram 負責的領域）的業務增值。至於糖尿病方面的問題，我來問 Dave。

Yes. I mean, I think the broader context here is important. These patients have severe uncontrolled gout. They are often facing amputations, for example, because of the severity of the disease. And so there are a large number of these patients that are currently not being served in the market in clinical practice. And so our focus is on reaching those patients where the quality of life impediments are quite significant and the effects of the drug can be quite dramatic in improving the disease course and improving that sort of quality of life. So that's the focus right now.

是的。我的意思是，我認為更廣泛的背景在這裡很重要。這些患者患有嚴重的、無法控制的痛風。例如，由於病情嚴重，他們常常面臨截肢。因此，目前市面上有許多這樣的患者無法在臨床實務中獲得治療。所以我們的重點是幫助那些生活品質受到嚴重影響的患者，因為這種藥物可以顯著改善他們的病情，並提高他們的生活品質。這就是我們目前的工作重點。

And I wouldn't get distracted by some of the other potential associations.

我不會被其他一些潛在的關聯所分散注意力。

Operator, I think we have 2 more calls in the log here. So why don't we take 2 more, and then we'll thank our colleagues and let them get on with the day.

接線員，我想我們這裡還有兩通電話要接。不如我們再接兩個吧，然後我們會感謝同事，讓他們繼續一天的工作。

Our next question comes from Tim Anderson from Wolfe Research.

我們的下一個問題來自 Wolfe Research 的 Tim Anderson。

On AMG 133, maybe this is a silly question, but is it at all possible that you can start Phase III in 2024? The main way to do this would be to do an early or interim look of sorts at the Phase II trial before the primary completion date. And I know you're guiding for topline on that in late '24.

關於AMG 133，也許這個問題有點傻，但你們有可能在2024年啟動第三階段試驗嗎？主要方法是在主要試驗完成日期之前，對第二階段試驗進行一次早期或中期評估。我知道你們預計在2024年底公佈整體數據。

Yes. I mean as we go through '24, we'll give guidance on when we expect the Phase III program to launch. As is customary in these programs, we will take an interim look. That will remain blinded. We will not release that externally because this is a 52-week study, but that will help at least guide our thinking. Also recall that the FDA requires a certain safety database before you launch Phase III trials here. And so as we get into next year and start to have those conversations, we'll be able to give more definitive guidance as to when you can expect the launch of the Phase III program and what that suite of studies might look like.

是的。我的意思是，在2024年，我們會就何時啟動III期臨床試驗給予指導。按照這些項目的慣例，我們會進行中期評估。中期評估將保持盲法，不會對外公佈，因為這是一項為期52週的研究，但至少可以幫助我們理清思路。另外，請記住，FDA要求在啟動III期臨床試驗之前建立一定的安全性資料庫。因此，隨著我們進入明年並開始進行相關討論，我們將能夠就何時啟動III期臨床試驗以及該系列研究的具體內容給出更明確的指導。

Our last question will come from Colin Bristow from UBS.

最後一個問題來自瑞銀集團的柯林布里斯托。

Maybe just a quick follow-up on 133. Just as we think about this from a commercial perspective, this is obviously an antibody backbone. It's going to be an injectable just in light of the margin that's achievable with this. Just help us think through that.

關於133，或許可以簡單跟進。從商業角度來看，這顯然是一種抗體骨架。考慮到它所能達到的利潤率，它將是一種注射劑。請您幫我們理清思路。

Well, Colin, you already pointed out that this is an antibody backbone. The properties of that, obviously, as I was alluding to earlier, could be that you can dose it much less frequently than you have to with the current therapies on the market. We also think, given the potential differentiation on efficacy and possibly tolerability that we'll be able to establish a very strong position in the market for people who need rapid, deep and sustained weight loss that they can manage over time so that they can gain the benefits, the reduction in cardiovascular risk, the improvement in outcomes from that treatment.

科林，你剛才已經指出，這是一種抗體骨架。正如我之前提到的，它的特性在於，與目前市面上的療法相比，給藥頻率可以大大降低。我們認為，考慮到其在療效和耐受性方面的潛在差異，我們將能夠在市場上佔據非常穩固的地位，為那些需要快速、深度且持久減重，並希望長期維持減重效果的人群提供解決方案，從而幫助他們獲得降低心血管風險、改善治療效果等益處。

But we expect, as Dave said, to develop this product across a suite of Phase III experiments, and we expect to be able to take a decent share of the market, which will drive a good return on our investment in that product.

但正如戴夫所說，我們期望透過一系列 III 期實驗來開發該產品，並期望能夠佔據相當可觀的市場份額，這將為我們在該產品上的投資帶來良好的回報。

I would now like to turn the call back over to Bob Bradway for closing remarks.

現在我謹將電話交還給鮑伯‧布拉德韋，請他作總結發言。

Okay. Well, let me thank all of you for joining us this morning, and we hope that the choice of doing this in the morning is for you to go enjoy the afternoon and evening of trick or treating wherever you are. But we, again, appreciate your support. It's been an eventful two months at Amgen, and we look forward to having an opportunity to regather with you and report on the fourth quarter when we get to the new year. Many thanks.

好的。首先，感謝各位今天上午的參與。我們希望大家選擇上午進行線上交流，是為了能好好享受下午和晚上的萬聖節「不給糖就搗蛋」活動。再次感謝大家的支持。安進公司過去的兩個月可謂精彩紛呈，我們期待在新年到來之際與大家再次相聚，共同報告第四季度的工作進展。非常感謝。

This concludes our 2023 Q3 earnings call. You may now disconnect.

本次2023年第三季財報電話會議到此結束。您可以斷開連線了。