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 Julianne，今天我將擔任安進 2023 年第三季財務業績電話會議的會議主持人。

(Operator Instructions)

（操作員說明）

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

現在我想介紹投資人關係副總裁賈斯汀‧克萊斯(Justin Claeys)。克萊斯先生，您現在可以開始了。

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.

謝謝朱麗安，早上好，歡迎參加我們的 2023 年第三季財報電話會議。鮑勃·布拉德威 (Bob Bradway) 將主持電話會議，隨後默多·戈登 (Murdo Gordon) 對我們的表現進行更廣泛的審查； Vikram Karnani，於 2023 年 10 月 6 日收購完成後從 Horizo​​​​n Therapeutics 加入安進；戴夫·里斯；和彼得·格里菲斯。

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括 Horizo​​n 的任何貢獻。 Vikram 將提供 Horizo​​​​n 第三季度產品銷售的精選信息，以供未來參考。您應該已經收到我們發布的幻燈片的連結。在今天的討論過程中，我們將做出一些前瞻性陳述，並使用非公認會計準則財務指標來描述我們的表現。只是提醒一下，實際結果可能會大不相同。

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

我現在想把電話轉給鮑伯。

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，也謝謝大家加入我們的電話會議。對於安進來說，這是一個激動人心的時刻，今年我們將繼續保持良好的執行力，為世界各地更多的患者提供Repatha、EVENITY 和TEZSPIRE 等藥物，並通過我們的管道快速推進許多有前景的一流藥物，為我們下一波生物相似藥的推出做好準備。

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，我認為我們可能會先將注意力轉向那裡。

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.

Horizo​​n 收購，加上我們一年多前收購的 ChemoCentryx，為安進提供了重要的罕見疾病業務，該業務完全符合我們的整體策略，並將促進我們對基礎業務的預期成長。當然，我們策略的核心是創新。首先，我們一流的藥物對患有嚴重疾病的患者有很大的幫助。我們的罕見疾病產品組合中的 TAVNEOS、TEPEZZA、KRYSTEXXA 和 UPLIZNA 等藥物完全符合這一描述，它們將受益於安進數十年在發炎性疾病方面的經驗。這些藥物還處於生命週期的早期階段，我們可以利用安進在製程開發、生命週期管理和製造方面的能力，對它們的成長產生積極影響。

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，我們在過去十年左右的時間裡拓展了我們的國際足跡，安進藥品現已在大約 100 個國家上市。如今，我們的罕見疾病銷售幾乎全部來自美國，因此我們將能夠利用我們的全球影響力，快速將這些藥物帶給世界各地的患者。您很快就會聽到維克拉姆·卡納尼(Vikram Karnani) 的更多信息，他通過收購Horizo​​​​n 加入我們，領導著一個新創建的罕見病業務，該業務現在是安進商業支柱的第四條腿，與我們的發炎、腫瘤和普通醫學業務並列。

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.

轉向我們本季的財務業績。與去年同期相比，總營收成長 4%，每股收益成長 6%。全球銷量成長了 11%，這代表我們連續第四個季度實現兩位數銷量成長，並且我們在所有地理區域和治療領域實現了良好的平衡。我們的七種藥物在本季度創造了創紀錄的銷售額，我將重點介紹其中的一種藥物 BLINCYTO，該藥物在第三季度實現了 55% 的銷售額增長。

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.

我們認為 BLINCYTO 具有持續的上升潛力，因為它越來越多地用於早期治療，並且更新了實踐指南以反映該藥物在治療廣泛的急性淋巴細胞白血病患者中所發揮的作用。

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 are in 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.

轉向我們的管道。最近，我們有機會在 ESMO 之後與您討論 6 個潛在的一流腫瘤學資產。其中三種藥物（tarlatamab、BLINCYTO 和 LUMAKRAS）與 Vectibix 聯合治療大腸直腸癌，獲得了 FDA 的突破性療法認定。我們也繼續推進 bemarituzumab 治療胃癌、Xaluritamig 治療前列腺癌和 AMG 193 的試驗，AMG 193 是我們的 PRMT5 抑制劑，已在 6 種實體瘤中產生了反應。

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.

我要快速指出的是，AMG 193 是透過我們專有的DNA 編碼庫技術識別出來的，該技術是我們在2019 年收購New Evolution 時添加的，它證明了我們在多特異性藥物新興領域的領導地位，這些藥物可以解決以下途徑：長期以來一直被認可，但被認為是傳統藥物發現工作無法實現的。

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.

在其他管道新聞中，我們已經完成了 Maridebart cafraglutide（以前稱為 AMG 133）的 II 期肥胖研究的入組。最後，FDA 已接受我們的 EYLEA 生物仿製藥的 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.

看看我們的業務，我們覺得我們的整體發展勢頭良好。我們擁有投資組合、通路和人員所需的一切，可以在本世紀末及以後實現具有吸引力的銷售和盈利增長。一如既往，我要感謝世界各地的安進員工，包括大約 2,000 名專注於罕見疾病的新同事，感謝他們為我們服務的患者提供強有力的執行力。

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

說到這裡，我現在將轉向默多·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。我對我們第三季的表現感到滿意。整個業務執行力強勁，7 個品牌的季度銷售額創歷史新高，我們的普通醫學、發炎和血液學/腫瘤學產品組合的銷量強勁增長。產品銷量較去年同期成長5%。我們各地區的銷量成長了 11%。美國銷量成長 11%，歐洲、拉丁美洲、中東和加拿大地區銷量成長 8%。根據我們的國際擴張策略，亞太地區仍然是我們成長最快的地區，本季銷量成長了 27%。

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.

從我們的普通醫學業務開始，其中包括 Repatha、Prolia、EVENITY 和 Aimovig。在銷售成長 20% 的推動下，第三季這 4 種產品的整體營收年增 21%。第三季 Repatha 銷售額年增 31%，銷售成長 44%，但部分被淨售價下降所抵銷。在美國，開始治療的新患者數量創歷史新高，比去年增加了一倍以上，推動了治療量增加 45%。我們看到美國的淨銷售價格下降，這主要是由於 CVS 7 月針對商業患者的新處方覆蓋所致。

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.

在美國以外的地區，我們的銷量成長了 43%，且表現強勁。世界各地還有更多的患者可以從 Repatha 中受益。我們正在透過投資和執行來提高醫生和患者的認識來應對這一挑戰。在美國，我們今年大幅擴大了初級保健銷售隊伍，並啟動了超過 15,000 名新處方醫生。我們也透過直接面向消費者的媒體努力加大對患者的宣傳力道。

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.

轉向骨骼健康領域，Prolia 第三季銷售額年增 14%，主要得益於 7% 的銷售成長和更高的淨售價。我們預計 Prolia 的銷售量將會成長，今年稍早公佈的真實世界證據數據證明，與阿崙膦酸鈉相比，Prolia 在降低停經後骨質疏鬆症初治患者骨折風險方面具有優越性。

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.

在銷售成長 48% 的推動下，EVENITY 本季銷售額達到創紀錄的 3.07 億美元。骨質疏鬆症對停經後婦女的影響尤其嚴重，而這些患者的診斷和治療率很低。到 2023 年，我們預計美國將有約 300 萬名患者接受停經後骨質疏鬆症治療。據估計，接受治療的患者中有 40% 的骨折風險非常高，但這些高風險患者中至少有 6% 將接受骨構建產品治療。

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 在骨骼增強劑市場中發揮重要作用，在美國佔有 58% 的份額，在日本佔有 44% 的份額。還有很多工作要做，我們將繼續投資，以確保 EVENITY 惠及有需要的患者。

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.

Otezla 銷售額年減 10%，原因是淨售價下降、預計銷售扣除額的不利變化以及庫存水平降低，但美國銷量增長 1% 部分抵消了 Otezla 淨價下降。並擴大商業和醫療保險D 部分患者的使用範圍。我們的美國 Otezla 業務受到了與進入牛皮癬市場的新治療方案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 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.

我們開始看到這些免費藥物計劃的影響正在減弱，因為考慮到這些新療法的事先授權要求，醫生和患者在獲得這些藥物方面遇到了障礙。我們對 Otezla 的成長潛力充滿信心。這種針對所有嚴重程度的銀屑病的獨特適應症，結合既定的臨床特徵、廣泛的支付者覆蓋範圍、缺乏啟動所需的測試和方便的口服給藥。為了實現這一潛力，我們增加了投資，以確保醫生和患者了解系統治療牛皮癬的重要性以及 Otezla 提供的安全性和有效性。

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.

我們已經看到了增加投資帶來的積極成果，包括請求教育資訊的患者數量顯著增加，並在 Otezla 網站上採取行動，這通常表明準備與醫療保健專業人員進行討論。最近，我們還將皮膚科銷售團隊增加了 20%，以向醫生宣傳 Otezla 對適當患者的益處。透過這些增加的投資，我們預計將推動 Otezla 恢復成長。

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.

ENBREL 銷售額年減 6%，主要是由於預期銷售額減少帶來的不利變化導致銷售額下降 8%。第三季治療量年增 1%，由於支付者覆蓋範圍的擴大以及 ENBREL 20 多年的安全性和有效性記錄，美國開始治療的新患者數量增加了 22%。在 2023 年剩餘時間內，我們預計覆蓋範圍的擴大將導致新患者數量持續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 持續保持強勁成長，第三季銷售額達 1.61 億美元。銷量環比增長 21%，銷量增長 18%，這得益於我們推出的自管理預填充一次性筆，該筆於第一季度獲得了美國食品和藥物管理局的批准。現在，我們已經獲得了大多數藥品福利管理者的認可，使美國患有嚴重不受控制的氣喘的患者能夠輕鬆使用和方便地進行自我管理。

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 已經滲透並幫助發展了美國氣喘生物製劑市場。 2023年，使用氣喘生物製劑的新患者數量較去年同期成長超過20%，TEZSPIRE在這一擴大的市場中的份額約為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.

TAVNEOS 本季銷售額為 3,700 萬美元，銷量較上季成長 26%。在美國，大約 2,300 名患者現已接受 1,500 多名醫療保健專業人員的 TAVNEOS 治療。我們不斷看到風濕病學家和腎臟科醫生對 TAVNEOS 的認識不斷提高。在本季結束時，我們看到新的患者開始表格增加。

Looking forward, we expect to bring TAVNEOS to even more patients with ANCA-associated vasculitis. AMGEVITA 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，我們預期將 TAVNEOS 帶給更多 ANCA 相關血管炎患者。在銷量成長 53% 的推動下，AMGEVITA 第三季銷售額年增 30%，但部分被淨售價下降所抵銷。在銷量成長 22% 的推動下，美國以外的銷售額成長了 10%，但淨售價下降部分抵消了這一影響。

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.

轉向我們的血液學/腫瘤學業務，包括 LUMAKRAS、KYPROLIS、XGEVA、Vectibix、Nplate 和 BLINCYTO。強大的商業執行力和引人注​​目的新臨床數據推動這 6 種創新產品的銷量年增 15%。 BLINCYTO 第三季銷售額年增 55%，達到創紀錄的 2.2 億美元。 2022 年末提交的註冊 E-1910 研究的積極數據以及 5 月發布的更新版 NCCN 指南帶來了積極的數據，為急性淋巴細胞白血病患者提供了廣泛的處方，支持了 56% 的銷量增長。從長遠來看，我們看到 BLINCYTO 較早療法具有顯著的額外成長潛力。

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 公佈第三季銷售額為 5,200 萬美元，年減 31%。其中 2200 萬美元的下降是由於法國正在進行的報銷談判所致。我們看到了 LUMAKRAS 在新市場的推出和我們全面的全球臨床開發計劃的推動下未來的成長機會。

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.

在淨售價上漲和銷量成長 4% 的推動下，Vectibix 第三季銷售額年增 2%，達到創紀錄的 2.52 億美元，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%，主要由 8% 的銷售成長推動。受惠於美國政府 1.42 億美元的訂單，Nplate 第三季銷售額年增 45%。第四季度，我們預計將履行美國政府向 Nplate 額外提供的 6,200 萬美元訂單。

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.

鑑於我們的血液學/腫瘤學產品的強勁表現以及在 ESMO 上展示的關於我們的腫瘤學產品線的令人興奮的新積極數據，我們期待幫助更多患者進行癌症治療。總體而言，我們整個業務的執行力很強，推動了成長並展示了我們對服務患者的奉獻精神。隨著我們罕見疾病產品組合的擴大，我們很高興能為世界各地更多可以從我們的治療中受益的患者提供服務。

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

有了這個，我會把它交給維克拉姆。

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。我們很高興將 Horizo​​n 的藥物、產品線和罕見疾病專業知識與安進在發炎性疾病、全球基礎設施和世界一流的生物能力方面的領導歷史相結合。對於那些不太熟悉 Horizo​​n 產品組合的人，我將在接下來的幾分鐘內提供一些有關我們罕見疾病藥物的背景知識。

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 業務第三季銷售額達 9.45 億美元，年增 2%，並具有多項積極的領先指標。讓我更詳細地描述一下。 TEPEZZA 是第一個也是唯一一個被批准用於治療甲狀腺眼疾的藥物，無論疾病活動度或持續時間如何，第三季度銷售額為 4.53 億美元，環比增長 2%。我們相信，隨著我們正式聯手並組建完整的商業團隊，隨著時間的推移，我們將在向患者推廣這項重要產品方面取得重大進展。我們正在推動多項舉措，以繼續建立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.

在第三季度，我們看到 TEPEZZA 處方者數量同比增長超過 50%，這得益於 2023 年 4 月 FDA 標籤更新的支持，用於治療甲狀腺眼疾患者，無論疾病活動度或持續時間如何。我們對這一進展感到高興，並將繼續向醫生群體提供關於所有 TED 患者的新臨床數據和更新適應症的教育。

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，大型國家和地區付款人正在繼續做出有利的政策改變，以幫助符合條件的患者獲得 TEPEZZA。到目前為止，我們已經為超過 30% 的美國受保人獲得了有利的政策變化，預計這些變化將於今年稍後和明年初生效。提醒一下，對於 TEPEZZA，確定接受 TEPEZZA 治療的患者與開始治療之間存在時間間隔。病患登記表最多可能需要 90 天才能完成事先授權流程。一旦完成該步驟，就需要將患者的輸液安排在適當的照護地點。這個過程需要時間，我們採取了幾個重要步驟來最大限度地縮短患者識別和治療開始之間的時間。

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，我們繼續在美國看到大約 10 萬名患有中度至重度疾病的患者適合 TEPEZZA，其中大多數患者處於低臨床活動評分環境中。因此，患者——FDA 的標籤更新，加上付款人有利的醫療政策變化，以及不斷擴大的處方醫生基礎的支持，為我們提供了接觸更多患者的重要機會。這些積極的執行趨勢增強了我們對 TEPEZZA 在美國成長潛力的信心。

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.

轉向美國以外的市場 我們仍然認為國際擴張對 TEPEZZA 來說是一個有意義的長期成長機會，該公司於今年第二季在巴西首次獲得美國批准。我們對有機會利用安進在美國以外多個主要市場的長期影響力感到特別興奮。包括歐洲和日本在內的市場，我們報告了 III 期 OPTIC-J 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.

我們也繼續在患有慢性或低臨床活性甲狀腺眼疾的日本患者中進行 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 是第一個也是唯一一個被批准用於治療不受控制的痛風的藥物，第三季度銷售額達到創紀錄的 2.53 億美元，同比增長 32%。目前年銷售額為 10 億美元。第三季的業績反映出風濕病學和腎臟病學領域的持續強勁成長。強勁的成果是由患者治療過程各個階段的執行、需求產生、利害關係人教育和堅持治療所推動的。 FDA 於 2022 年 7 月批准了 KRYSTEXXA 與甲氨蝶呤聯合用藥的標籤變更。自那時以來，我們看到其使用量穩步增加。

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.

第三季新患者中免疫調節劑的使用率仍維持在 70% 以上。我們看到了用甲胺蝶呤重新定義 KRYSTEXXA 作為護理標準的機會，並惠及美國超過 10 萬名未受控制的痛風患者。

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。國際擴張也正在進行中，UPLIZNA 現已在美國以外的多個市場推出，包括德國、法國、義大利、西班牙和巴西。正在開發的其​​他適應症也支持 UPLIZNA 的長期成長潛力，針對 IgG4 相關疾病和重症肌無力的 III 期試驗正在進行中。

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 的其他產品組合在第三季度創造了 1.73 億美元的銷售額，主要是由我們的超稀有藥物 RAVICTI、PROCYSBI 和 ACTIMMUNE 組合推動的。我們看到這一系列產品有機會繼續產生強勁的銷售。

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.

在將其轉交給 Dave Reese 之前，我想藉此機會感謝罕見疾病業務的所有同事，感謝他們在過去幾個月的分心時期保持對患者的關注。展望未來，我們很高興能夠利用安進和 Horizo​​​​n 的綜合能力進行合作，確保我們的藥物更快地惠及全球更多患有嚴重和罕見疾病的患者。

I'll now turn it over to Dave.

我現在把它交給戴夫。

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.

謝謝你，維克拉姆，大家早安。首先我要歡迎 Horizo​​​​n 的新同事。我們很高興能夠將 Horizo​​​​n 的研發能力與安進的研發能力相結合，以推進前景光明的 Horizo​​​​n 管道。對於研發來說，第三季是高品質執行的季度之一，因為我們透過重要的腫瘤學數據讀數、增加了2 個突破性治療指定以及完成了關鍵研究的入組，推進了我們的創新管道。我們也透過快速註冊多項支援註冊的研究來推進我們的創新管道。

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.

從普通醫學開始。我們已經完成了 Maridebart 卡夫拉魯肽針對患有或不患有糖尿病的肥胖患者的 II 期研究的入組。這項研究的目標是產生數據，為設計廣泛的 III 期計畫提供選擇性，利用 Maridebart 卡夫拉魯肽的獨特特性，這可能使我們能夠採取差異化的方法。我們預計這項為期 52 週的研究將於 2024 年底獲得主要數據。

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.

Olpasiran 是我們潛在的同類最佳 Lp(a)，針對動脈粥狀硬化性心血管疾病中的小幹擾 RNA 分子，其 III 期結果研究的招募情況非常順利。在發炎方面，除了嚴重氣喘之外，我們正在研究 TEZSPIRE 的其他適應症，包括完全入組的慢性鼻竇炎伴鼻息肉和嗜酸粒細胞性食道炎的單獨 III 期研究。我們還有一項針對COPD 的II 期研究，該研究已全部入組，預計將於2024 年上半年獲得主要數據。這項研究招募了廣泛的COPD 患者，包括嗜酸性粒細胞計數高和低的患者。

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 是一種一流的抗 OX40 單株抗體，正在中度至重度異位性皮膚炎患者中進行研究，ROCKET III 期臨床開發計劃的招募工作已經有了一個良好的開端。

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，我們已在該計畫中對 1,500 多名患者進行了隨機分組。我們很高興在收購Horizo​​​​n 後展示來自我們擴展的風濕病學產品組合的更多數據，包括來自Dazodalibep 和乾燥綜合徵的II 期研究的數據，以及來自KRYSTEXXA、TAVNEOS、Otezla 和來自美國學院廣泛產品組合的其他分子的資料風濕病學聯盟 2023 年 11 月會議。

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.

鑑於上週詳細的腫瘤學回顧，我將簡要介紹我們的腫瘤學投資組合。基於 E-1910 III 期研究，FDA 已授予 BLINCYTO 突破性療法稱號，用於在多階段治療的鞏固階段治療 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。我們看到 BLINCYTO 的未來成長來自於早期治療和皮下給藥系列的進步。 BLINCYTO 也為我們規劃如何將 tarlatamab 和 Xaluritamig 快速推進早期治療並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.

與該領域的專家一起，我們對 tarlatamab（我們的靶向 DLL3 的 BiTE 分子）感到非常鼓舞。在ESMO，我們展示了DeLLphi-301 的數據，這是一項針對晚期小細胞肺癌的II 期研究，在患者通常選擇有限且預後極差的環境中，我們看到了令人印象深刻的緩解率、緩解持久性和整體存活率。我們正在向 FDA 提交這些數據，並且很高興 FDA 已授予 tarlatamab 突破性療法指定，用於治療在鉑類化療期間或之後疾病進展的廣泛期小細胞肺癌成年患者。鑑於我們對這些數據的信心，我們正在迅速將 tarlatamab 推進到早期治療領域，多項 III 期研究正在進行或計劃中。

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.

根據新出現的臨床數據，我們將停用 PSMA 靶向雙特異性 AMG 340，我們將專注於快速推進 Xaluritamig 在轉移性去勢抵抗性前列腺癌的應用。我們預計 Xaluritamig 劑量擴展隊列將在今年年底前全部入組，並計劃在早期前列腺癌患者中啟動更多研究。

With AMG 193, a small molecule MTA cooperative PRMT5 inhibitor, we're encouraged by the responses we've seen across 6 MTAP in all 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，我們對所有實體瘤中 6 個 MTAP 的反應、可管理的安全性和 CNS 滲透劑的臨床前證據感到鼓舞。我們現在正在快速招募劑量擴展隊列。

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

有了這個，我會把事情交給彼得來了解最新的財務狀況。

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.

謝謝你，戴夫。在討論我們更新的 2023 年指導之前，我將回顧我們的第三季業績。轉向我們第三季的財務業績，如幻燈片 44 所示。總收入為 69 億美元，年增 4%，非 GAAP 每股收益為 4.96 美元，年增 6%。營收成長歸因於產品銷量年增 5%，銷量成長 11%。

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.

第三季非公認會計原則營運支出總額較去年同期成長 4%。我們在本季度推進了我們的產品線並投資於成長機會，同時實現了非 GAAP 營業利潤率（佔產品銷售額的 52%）。非 GAAP 銷售成本佔產品銷售額的百分比年增 1.3 個百分點，達到 17.4%，主要是由於利潤份額增加和產品組合變化所致。由於研究和早期研發活動支出減少，本季非 GAAP 研發費用年減 2%，但部分被後期臨床項目和上市產品支出增加所抵銷。

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，由於後期臨床項目和上市產品支出增加，非 GAAP 研發費用增加了 5%，但部分被研究和早期研發支出減少所抵消。第三季非 GAAP SG&A 費用年增 1%。我們繼續專注於優先考慮關鍵投資、數位化、提高生產力和加速人工智慧的用例。第三季非 GAAP OI&E 淨支出為 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.

與去年同期相比的好感度主要是由於利息收入的增加以及北京會計從權益法改為按市值計價投資的變化（其影響僅包含在我們的公認會計原則結果中）。我們第三季的非公認會計準則稅率增加了 3.2 個百分點，達到 16.1%，這主要是由於 2022 年波多黎各稅法變更，從 2023 年開始用所得稅取代消費稅。

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.

我們繼續執行我們的資本配置優先事項。首先，我們持續優先投資內部和外部創新。第三季我們加大了專案的投資，包括Maridebart卡夫拉魯肽，我以後就叫它Mari；羅卡汀利馬布；塔夫尼奧斯；和 ABP-206，我們的生物相似藥；到奧狄沃。其次，我們繼續投資我們的業務以實現長期成長，包括在俄亥俄州和北卡羅來納州同時建造最先進的製造設施。我們對俄亥俄州工廠預計將於 2024 年上半年獲得許可感到興奮。此外，我們正在對業務的各個部分進行投資，以利用生成式 AI 機會的力量。

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，我們在向股東返還資本方面有著良好的記錄，並在第三季度支付了每股2.13 美元的股息，比2022 年第三季度增長了10%。該公司在第三季度產生了25 億美元的自由現金流。2023 年第三季的營收為 28 億美元，而 2022 年第三季為 28 億美元。我們將繼續產生強勁的現金流。然而，由於納稅時間和 Horizo​​​​n 交易相關費用，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.

轉向幻燈片 46 上的 2023 年業務前景。我們很高興完成了對 Horizo​​​​n Therapeutics 的收購。我們正在更新 2023 年全年指引，以納入自 2023 年 10 月 6 日起的 Horizo​​​​n 財務業績。因此，我們第四季度的業績將排除 Horizo​​​​n 大約 1 週的業績。我們將 2023 年收入指引上調至 280 億至 284 億美元，而先前的指引為 266 億至 274 億美元。對於 2023 年非 GAAP 每股收益，我們將範圍縮小至 18.20 美元至 18.80 美元，而先前的指引為 17.80 美元至 18.80 美元。我們將把 Horizo​​​​n 的業務納入第四季度，且不會對非 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，我們確實預計第四季度非GAAP 每股收益將低於第三季非GAAP 每股收益，因為我們計劃增加業務投資，包括從Mari、Olpasiran 和AMG 193 開始的創新管道中的關鍵資產以及其他策略性業務投資，包括我們業務的各個部分都使用生成式人工智慧用例。這種連續模式與歷史趨勢是一致的。

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，第四季非 GAAP 每股盈餘將開始將與 Horizo​​n 融資相關的利息費用確認為非 GAAP 費用。在對 2023 年剩餘時間進行建模時需要考慮的重要其他要點。我們現在預計 2023 年的其他收入將在 12 億美元至 13 億美元之間，而之前的範圍為 11 億美元至 13 億美元。透過收購 Horizo​​n，我們現在預計 2023 年全年非 GAAP 營運費用將從我們之前估計的 3% 增加到去年的約 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 約佔這 10% 年成長的 5 個百分點。我們繼續預期 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在 16% 至 17% 之間。我們現在預計我們的非 GAAP 研發費用將從先前指導的 5% 年增至 10% 左右。 Horizo​​n 約佔這 10% 年成長的 3 個百分點。額外的 2 個百分點是由於我們計劃增加對創新產品線的投資，包括 Mari、Olpasiran 和 AMG 193。我們繼續預期非 GAAP SG&A 在產品銷售額中所佔的百分比將比去年同期略有下降。

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 OI&E 支出將在 14 億美元至 15 億美元之間，高於我們先前指引的 11 億美元至 12 億美元。我們預計第四季度的 OI&E 約為 7 億美元，反映了與 Horizo​​​​n 融資相關的利息支出，該利息支出將包含在我們 10 月 6 日生效的非 GAAP 業績中。

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.

當您開始對 2024 年進行建模時，請注意，我們預計 2024 年 OI&E 將與第四季度的運行率保持一致。較高的利息支出是由於收購 Horizo​​n 所籌集的 280 億美元債務造成的，加權平均利率為 5.6%。我們預計到 2023 年底，長期債務約為 650 億美元，包括當前部分以及 110 億美元的現金和現金等價物。對於全年，我們預計非 GAAP 稅率為 16.5% 至 17%，低於先前指引的 17.5% 至 18.5%。我們預計第四季流通股數約為 5.4 億股。第三季的成長是由於未歸屬的 Horizo​​n 股權獎勵轉換為安進股權獎勵所致。我們 2023 年的資本支出預計約為 9.5 億美元，高於我們先前指引的 9.25 億美元。

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。我們持續分配資金，以快速、大規模地推動創新。我非常感謝我們現在 26,000 多名同事成功地履行了我們為患者服務的使命。財務更新到此結束。

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 Julianne 打開問答線路，並提醒我們的參與者提問的程序。朱麗安？

(Operator Instructions)

（操作員說明）

Our first question comes from Michael Yee from Jefferies.

我們的第一個問題來自 Jefferies 的 Michael Yee。

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?

感謝您提供有關 Horizo​​n 交易的所有詳細資訊。我只是想問大衛·里斯一個問題。我的意思是，大衛，除非我們躲在岩石下，否則我想，肥胖就像是現在最大的事情，我想了解您對 133 的評論和信心，以及您認為與領導者相關的概況考慮到其他口試的門檻如此之高，786 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 peptide stapled to the molecule for that mechanism of action.

是的，當然。正如我們之前與 133 討論過的，Mike，我們相信我們有一個基於作用機制的潛在差異化產品。它具有雙重功能，提醒大家，根據我們主要透過將 2 個 GLP-1 肽釘在分子上以實現該作用機制的遺傳證據來拮抗 GIPR。

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.

正如我在評論中指出的，我們已經迅速啟動了二期試驗。這項試驗有多個組，探索 3 種不同的劑量以及不同的給藥間隔，我認為這將為我們提供廣泛的選擇。我們對第一階段的數據在反應深度、反應動力學以及持久性方面非常滿意。這些是我們在前進過程中將在第二階段關注的事情。因此，該計劃正在全力推進，我們期待明年第二階段試驗的數據，這將真正告知我們正在考慮的第三階段試驗的廣度，這可能會相當困難。

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 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。正如我們在明年上半年所表明的那樣，我們正在引入數據，因此我們預計將展示這些數據並確定前進的道路。正如您所指出的，這是該領域的一個很高的標準，我們必須看到那種概況，這將使我們有信心廣泛投資於此類分子。我還要指出的是，我們已經有了一套臨床前分子，其中許多是基於我們將在未來幾年推出的作用機制的非腸促胰島素。因此，我們預計該領域將成為長期參與者。

Our next question comes from Yaron Werber from Cowen.

我們的下一個問題來自 Cowen 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.

偉大的。彼得，就你而言，7 億美元的營運費用只是利息支出，對嗎？這還不包括您在其他收入方面記錄的北京貢獻。其次，在您的指導下，您也提到同比增長 3% 到 10%，並提到 5% 到 10% 用於研發。 3% 到 10% 的成長只是提醒我們這是因為 SG&A 預計會比去年同期略有下降。所以我只是想念那是什麼。

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.

正確的。謝謝你，亞龍。 7億美元就是一切。這就是完整的運行率。關於你關於研發的問題，正如我在發言中所說，我們將支出集中在後期的臨床和市場投資組合上，這被早期研究的一些減少所略微抵消，但我們繼續支出和投資於業務，我們將繼續這樣做。正如您所看到的，我們很幸運在第三階段的後期階段擁有大量機會。這就是我們將繼續關注的重點。我們將繼續對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.

我們的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?

偉大的。也許我也為彼得準備了兩首曲子。彼得，再說一次，我知道你最後讀了很多數字。但就今年的收入指導成長而言，您能否描述一下這是否全部來自 Horizo​​​​n 投資組合，或者是否有來自基礎基礎業務的任何其他貢獻？

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?

然後問題的第二部分是關於如何思考 2024 年稅率的任何方向性幫助，因為我知道一些立法中有許多變化，但顯然 Horizo​​​​n 交易已經接近尾聲了。那麼就方向性而言，您能幫我們解決 2024 年的稅率問題嗎？

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 OEC, the 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。那麼關於稅率，讓我從2024年的稅率開始。我們將像年初一樣對此進行指導。我只想說，我認為您正在考慮第二支柱中的全球最低稅，我只想指出，對於整個 OEC 框架將如何實施，沒有共識或可預測。我知道不同的國家正在做不同的情況。請放心，我們會考慮一切，在類似的事情上適當地優化我們的立場。因此，我們將在明年年初為您提供相關指導。問題的第一部分？

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。在收入方面，看，我們並沒有真正細分。我只是建議我們繼續看到業務的實力。我們繼續看到我們的內嵌投資組合表現非常非常好。我只想指出，我們有 7 種產品在本季創下了銷售記錄。我們的 Repatha 在本季同比增長了 31%，我們繼續看到血液學/腫瘤學組合增加了 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.

所以我們的基礎業務一切都很強大。我們對這個基礎業務感到興奮。它的表現仍然非常出色，我們很高興現在擁有罕見疾病業務。正如我們所說，期待這一點是我們商業推進的第四個凳子。因此，我們看到不同領域的業務都具有良好的實力，我們將繼續為患者提供越來越多的藥物。

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%.

我要指出的是，11% 的銷量成長非常重要，低於美國以外地區 12% 的銷量成長，以及我們成長最快的地區 JPAC 27% 的銷量成長。這就是我們的看法。我們對這一勢頭感到滿意，並且很高興能夠將 28.0% 提高到 28.4%。

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。

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?

至於 Horizo​​n 交易現已結束，您能否簡單介紹一下我們對 2024 年 TEPEZZA 和其他資產的展望？您談到了必須擴大美國以外地區患者人數的舉措，作為成長槓桿。也許可以引導我們完成這個過程，以及我們什麼時候可以獲得更新的長期指導，包括地平線？

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。也許我們可以把這個分成兩個部分，Salveen，我是 Bob。顯然，我們今天早上不會在這裡提供 24 小時指導。但當我們審視明年的這些產品時，我們會看看是否能讓您清楚地了解哪些讓我們興奮的事情。一般而言，關於長期指導的問題。正如您在多個場合聽到我們所說的那樣，我們仍然有信心，我們有望實現或超越我們為2030 年制定的目標。坦白說，現在在某些方面，我們更專注於我們能夠做到的事情交付到 2031 年，很快也將到 2032 年。

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.

因此，幾週前我們與您深入回顧了腫瘤學投資組合，這讓您對本世紀末的動態有了很好的了解。我們可能會尋求以這種方式展示明年的業務概況，以便您可以更全面地深入了解推動成長的業務的不同部分。但讓我們轉向你的第一個問題，即 Horizo​​n 的前景和正在進行的舉措，特別是 TEPEZZA、KRYSTEXXA、UPLIZNA 方面的舉措。

So Vikram, why don't you fire away?

那麼維克拉姆，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 cash setting or the low clinical activity score setting, can now access TEPEZZA.

是的。謝謝你的提問。我認為，正如我在準備好的發言中所說，在我們審視業務時，我們有很多積極的領先指標。我從 TEPEZZA 開始，在 FDA 2023 年 4 月標籤更新後，我們將繼續打造美國 TED 市場。這確實有助於我們為 TED 患者提供藥物，無論疾病活動度或持續時間如何。我們在標籤更新後看到的是，付款人正在繼續更新他們的醫療政策並使其更加優惠，以便更多這些患者，更多處於低現金環境或低臨床活動評分環境中，現在可以訪問泰佩扎。

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.

我認為最後，從執行的角度來看，我們看到眼科醫生和內分泌科醫生的新處方者在第三季度同比增加了 50%。因此，TEPEZZA 的所有這些指標都是積極的，我們對團隊的執行感到滿意。正如我所說，我們現在已經與安進聯手。我們應該能夠共同推動業務以積極的方式向前發展。

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——談論——圍繞 TEPEZZA 的故事也是國際成長的故事之一。雖然我們在美國看到了很多積極的趨勢，但我們對於作為一家合併公司也能為美國以外的患者所做的事情感到非常興奮。我們最近討論過巴西獲得批准的事情。

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試驗——OPTIC-J，我們已經討論了一項正在招募的慢性試驗，最後，我們正在為其他市場做好準備，我們希望現在將該藥物帶到更多市場作為合併後公司的一部分，而不是我們之前討論的。因此，TEPEZZA 在美國和全球都表現出非常積極的一面。

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 of Amgen.

正如我們討論 KRYSTEXXA 和 UPLIZNA 的結果一樣，這兩種藥物的效果都非常非常好。自去年標籤更新以來，我們的免疫調節以 KRYSTEXXA 為主要驅動力。自那時以來，這一直持續推動著人們的採用。我們看到這種情況將持續到未來。 UPLIZNA 是治療視神經脊髓炎譜系疾病(NMOSD) 中成長最快的生物製劑，我們看到這種勢頭在美國和美國以外的地區都在持續。所以我認為，當我審視整個產品組合時，我們— —我們的營運實力雄厚，現在我們可以透過與安進的合併進一步擴大這一優勢。

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?

祝賀在許多方面取得的所有進展。您能否談談您對人工智慧技術的投資以及這對您未來 5 到 10 年的藥物發現和開發有何影響？

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

當然。傑伊，我會請戴夫·里斯解決這個問題。

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。這是我們非常興奮的領域。我想將其描述為一個關鍵時刻，我們將看到技術和生物技術的走在一起或統一。我真的認為，隨著時間的推移，這將影響我們進行藥物發現和開發的方式發生質的變化。

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超大數據集的多組學分析，這一切都只能透過人工智慧或機器學習、密集的臨床試驗數據以及現實世界數據中的真實世界證據來處理。 。當你縱觀整個範圍時，我相信我們可能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，我們正在使用工具和基礎模型來真正挖掘這些數據，以獲得對生物學更深入的見解，然後一路進入市場。隨著時間的推移，我們將更多地討論這個問題，但這將是一個投資領域。它可能被誇大了。它不是萬能藥，但它絕對將成為我們在很長一段時間內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.

戴夫，我有一個關於 AMG 786（治療肥胖症的口服藥物）的問題，分為兩部分。首先，我注意到你們在試驗的 SAD 部分中放棄了一個隊列。那是因為你遇到了MTB嗎？然後，我還注意到圍繞自殺意念的排除標準得到了加強，我不知道我們是否可以對此進行解讀。很想得到任何顏色。

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，烏默。對於後者，我根本不會想太多。我不認為那裡有什麼。就我們所做的劑量而言，正如我們所指出的那樣，隨著我們進行第一階段試驗，這總是會進行調整，我們現在正在引入數據。我們正在研究這一點以及一系列臨床數據和更新的臨床前數據。我認為，當我們進入明年時，我們會把所有這些都放在一起，這將決定 AMG 786 的潛在前進道路。只是提醒大家，這個目標不是基於腸促胰素的目標。

Our next question comes from Robyn Karnauskas from Truist Securities.

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

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?

實際上我只是對 Salveen 的問題進行了跟進。所以TEZSPIRE並沒有獲得很多市場份額。 TED 領域有很大的發展空間。你能否向我介紹一下安進如何真正幫助發展該業務，因為我很困惑，到底是聽力損失還是報銷，或者真正發展該公司的槓桿是什麼——發展該業務，它是，TEPEZZA，抱歉，泰佩札。但我認為有很大的成長空間，並且只要你有力量，你就可以做到這一點。那你打算怎麼做呢？

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，羅賓。所以我認為 TEPEZZA 中的問題分為兩部分。我們可以分成兩部分來解決，維克拉姆和默多的組合。所以請繼續。維克拉姆，你為什麼不開始呢？

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——早些時候，我認為今年發生的事情之一是 FDA 的更新。現在，當標籤更新為無論疾病活動度或持續時間如何的患者時，其中許多患者，正如我要說的，更多的患者正在接受內分泌科醫生和眼科醫生等處方醫生的治療。這就是團隊一直致力於確保我們的教育計劃可供這些醫生使用的地方，以便我們能夠從最初開始治療患者的原始處方者群體中擴大我們的處方者基礎。因此，了解擴大處方者基礎是未來成功的關鍵驅動力非常重要。

And as we've seen, new prescribers have increased 50% year-over-year. As we continue to work through these -- this low cash 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.

正如我們所看到的，新開處方者比去年同期增加了 50%。當我們繼續解決這些低現金或低臨床活動患者的問題時，我們還必須記住，當他們開出藥物時，付款人需要開放獲得藥物的管道。因此，我們的市場准入團隊一直在非常努力地工作，以確保付款人繼續更新他們的醫療政策。我們看到，超過 30% 的美國受保人現在有資格接受 TEPEZZA 的治療，並享受更開放或更優惠的政策。這必須繼續下去。進入明年初及以後，我們將繼續致力於這兩個領域。

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

也許我會把它交給默多來添加他的評論。

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，維克拉姆。 Robyn，我想補充一點，當我們收購 ChemoCentryx 和 TAVNEOS 時，我們意識到人們對 TAVNEOS 的認知度很低。我們所做的就是向一些更廣泛的風濕病銷售人員添加了提醒訊息，以提高對 TAVNEOS 和 ANCA 相關血管炎患者相關數據的認識，當然，我們已經看到利用率相應增加，這是由對該產品的認知度。

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，核心團隊仍在宣傳產品的屬性並對醫生進行教育，但有更廣泛的現場人員群體在建立對該產品的普遍認識。我認為，Vikram 和我正在談論的是由參與甲狀腺眼疾診斷和治療的內分泌科醫生組成的安進團隊，這對我們來說是一個理想的機會，可以擴大診斷和治療甲狀腺疾病的內分泌科醫生社區的認識。今天，我們將加強 Vikram 領導下的罕見疾病團隊所做的偉大工作。

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，我們可以在許多類似的事情上擴展和加速意識的建立，例如維克拉姆剛剛描述的新數據以及標籤語言的拓寬。

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.

維克拉姆也提到了國際擴張。 Horizo​​n 最初的計劃是相當雄心勃勃的。實際上，我們已經增加了打算在更短的時間內提交和啟動的市場數量。因此，考慮到兩家公司現在合併後的實力，這將是一個額外的成長機會。

Might just add also, Robyn, that in terms of the time course of events here, I think now that we flex 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.

Robyn，我還可以補充一點，就這裡事件的時間進程而言，我認為現在我們回退了一年的 ChemoCentryx 所有權，我們真的可以開始看到 Murdo 剛才描述的好處，在過去幾周和幾個月。所以這需要一點時間，但我認為我們的信心是，在那段時間裡，我們已經能夠找到為該產品增加獨特價值的方法。我們希望我們引入的新罕見疾病分子也會發生類似的情況。因此，這並不像走進來，按下電燈開關，突然事情就在不同的軌道上進行，而是進來，一起工作，找出我們可以在市場上增加的方式。我希望我們能夠在 24 年期間看到合併後的組織在這些產品上的勢頭增強。

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腔肥胖的發展。關於一期候選藥物786，管理階層一直強調其還有一套口服臨床前產品。那麼，我們應該將 786 視為一個通配符，而不是安進目前所堅信的東西嗎？您預計什麼時候能夠開始另一個口服臨床前候選藥物的第一階段，這可能會在 24 年發生，還是要到 25 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?

然後，我想簡單地提出一個財務問題。您預計第四季度 Horizo​​n 產品通路庫存下降是否會嚴重限制第四季度報告的 Horizo​​​​n 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，大衛。戴夫·里斯，我先開始，然後把事情交給默多和維克拉姆。就口腔肥胖分子而言，786，如我所說，它有一個新穎的作用機制。它是 I 相分子。因此，您應該將其視為第一階段分子，我們正在引入 - 正如我所說的數據，我們將在進入新的一年時對其進行研究，並確定潛在的前進道路那個分子。我不會將其視為具有新穎作用機制的第一階段資產。就其他分子而言，當我們可能提交 IND 並啟動首次人體試驗時，我們將隨著該產品組合隨著時間的推移而進展提供指導。

Again, many of those molecules are targets that 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.

同樣，其中許多分子都是來自我們在冰島的同事 deCODE Genetics 的目標，當我們準備好進入臨床時，我將提供進一步的資訊。但這是一場持久戰。如果退一步看，這個領域還處於起步階段。我們才剛開始了解肥胖所發生的複雜代謝安排，肥胖顯然有不同的形式。還有很多工作要做。正如我所指出的，鑑於這是 21 世紀主要的公共衛生挑戰之一，我們的目的是打持久戰。

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

現在讓我把它交給維克拉姆和默多，讓他們對你的第二個問題進行補充評論。

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，大衛，我只是想確保我沒有聽錯你的問題，這是關於庫存和產品縮減的。聽著，我認為我們不會就這個具體方面發表評論。我認為 - 我們的團隊仍然專注於推動需求並與醫生合作對他們進行教育並擴大 TEPEZZA 對適當患者的使用。這就是我們真正關注的淨銷售額成長的主要驅動力。

Our next question comes from Chris Raymond from Piper Sandler.

我們的下一個問題來自 Piper Sandler 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——也許是關於你們的皮膚科策略的商業問題。特別是在 Otezla 上，就你們談論的免費競爭對手藥物的動態而言。據推測，這就是 SOTYKTU 的場景。我想我聽到你們已經提出這個問題有一段時間了，而且隨著你們對皮膚科銷售隊伍的投資，我想我聽到你們說今天你們正在增加銷售隊伍20%左右。這是否意味著一旦無競爭藥物計畫結束，Otezla 的銷售就應該增加？或者你對成交量的變化有什麼感覺？也許我會用另一種方​​式問。如果銷售成長沒有實現，您是否需要額外的皮膚產品組合產品來支持額外的努力？

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。因此，讓我們回顧一下這個市場正在發生的事情。今年年初，我們推出了許多新產品，不僅是 SOTYKTU 進入市場，還有新穎的口服藥物，而且每種產品都有非常慷慨的免費藥物計劃。這對奧特茲拉產生了兩個影響。有些局部患者通常會選擇第一個全身性治療方案，但他們在免費藥物的基礎上嘗試了新的局部治療。同時，也推出了一種新的口服藥物，其中有一個非常慷慨的免費藥物計劃。

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 的大部分成長來自於局部患者（首先是全身性患者），換句話說，是未使用過生物製劑的患者，Otezla 在第一季和第二季因進入市場的新項目而受到擠壓。

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.

自從市場上的這兩起事件以來，我們看到的是，新穎的主題的增長已經趨於平緩，並且在一定程度上減少了免費藥品的提供。

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 drugs program to continue to reduce and that will help us grow Otezla.

另一種口服療法，SOTYKTU繼續提供免費藥物。因此，它繼續對 Otezla 產生一些影響。我們認為將會發生的事情並且我們已經看到了非常早期的信號，即我們將繼續從局部患者（未進行過生物治療的患者）中獲取新的增長點，因為 Otezla 是全身藥物的理想選擇。我們已經在市場上建立了強大的影響力。因此，我們不需要像其他人一樣提供免費藥物計劃。然後，隨著 2024 年合約週期的成熟，我們看到市場上其他一些競爭對手（包括新口服）的實際准入情況，我們應該能夠對我們未來的成長前景提供更好的指導。但我們幾乎肯定預計免費藥品計劃的影響將繼續減少，這將有助於我們發展 Otezla。

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.

我們所做的投資在本季才真正開始發揮作用。因此，現場人員和人數的擴張是正確的 20%。 derm 團隊在第四季初剛部署。所以他們只在現場待了幾週。因此，這種影響並不影響該品牌的歷史表現，而且我們第四季的直接面向消費者的支出也有所增加。因此，隨著我們的進展，我們將能夠告訴您更多。但我們認為，考慮到這裡有大量患者在確實更適合全身用藥時繼續堅持局部用藥，隨著我們進入該市場，他們將轉向 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.

提醒一下，我們是市面上唯一具有廣泛標籤的產品，無論牛皮癬的嚴重程度如何。因此，我們感到樂觀和熱情，這就是我們進行這些投資的原因，隨著我們的前進，我們將繼續尋求增加我們的皮膚科產品組合。

Our next question comes from Mohit Bansal from Wells Fargo.

我們的下一個問題來自富國銀行的 Mohit Bansal。

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?

所以也許有一個關於連續成長的問題。如果我從第三季度看第二季度，似乎幾乎所有產品，甚至包括（聽不清楚）政府預算帳戶似乎都在下降。我知道您在第二季有關醫療保險甜甜圈漏洞的電話會議中警告過這一點，但您能談談那裡的動態嗎？我們該如何思考未來的發展？

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 hemo portfolio, BLINCYTO in particular.

是的。莫希特，我不認為所有產品都下降了。我認為我們有許多產品在本季度實現了相當顯著的兩位數增長，我們繼續預計 Repatha、EVENITY、Prolia、我們的血液產品組合、特別是 BLINCYTO 等產品將實現長期增長。

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，我們看到了我們的優先成長品牌的一些優勢，我們預計將繼續推動這些優勢。我們在本季確實對上一季的淨銷售額進行了一些調整。因此，根據我們在報銷方面的談判逐年變化，對 LUMAKRAS 進行了一項特別調整。例如，在法國，我們有一個早期臨時訪問計劃，即 ATU 計劃。自 2021 年以來，LUMAKRAS 已在法國上市，根據我們在法國進行的價格談判，我們在本季度從這些銷售中獲得了 2,200 萬美元的應計收益。

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.

因此，本季我們發生了許多與價格相關的事件。正如您所提到的，我們正在進入一些產品的甜甜圈洞。因此，總的來說，我認為單位銷售成長非常強勁，對投資組合中的某些產品有一些價格影響，還有一點甜甜圈洞的影響。

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

我們的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（Gregory Renza）。

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.

祝賀取得的進展。鮑勃，再次回到肥胖市場，您和團隊專注於真正做到最好——在市場上成為第一和/或同類最佳。我只是好奇您和您的團隊如何看待和預測肥胖市場可能會有多大的不同，以及您如何看待未滿足的需求隨著時間的推移而變化——安進的一個項目已經準備好迎接黃金時段了？但是，是否需要不僅從內部著眼，還從外部著眼來加速這些努力，尤其是在事情發展如此之快的情況下？祝賀取得的進展。

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.

我們對迄今為止在肥胖方面的早期工作所取得的成果感到非常興奮。我想隨著時間的推移，你會從 Dave Reese 那裡感受到這一點，這很可能是一種異質性疾病。可能需要採取多種不同的方法來實現這一目標。

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

但現在鼓勵我們的是我們認為我們的方法相對於競爭對手正在出現的差異化形象。

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?

也許默多，您是否想插話並提醒格雷戈里我們迄今為止在競爭對手的數據中看到的差異化基礎，以及為什麼我們認為這為我們進入市場提供了良好的立足點？

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。我喜歡這個問題的提出方式，有時會被提出如何處理市場上這些根深蒂固的產品。我只是希望（聽不清楚）人們了解（聽不清楚）市場現狀以及還有多少東西有待展開。我們早期看到的是，我們看到很多患者嘗試使用這些產品減肥，但隨後沒有堅持治療並恢復體重。因此，我們認為，從長遠來看，市場上有一個機會，可以找到一種能夠帶來非常強的減肥效果的產品，這種減肥效果既快速又持續，而且劑量方便。

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，這就是 133 或 Maridebart 卡夫拉魯肽真正有機會從當今市場上現有產品中脫穎而出的地方。我們已經看到該產品在劑量之間的耐久性。我們認為，根據第二階段以及我們在該試驗中探索的不同劑量組的數量，我們將能夠在功效和基於方便劑量的能力之間找到適當的平衡，以隨著時間的推移維持體重減輕。當然，這裡的目標不僅僅是減肥，而是改善一生中體重超標的人的一些後遺症或結果。

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.

這就是我們在其他人在賽事試驗中看到的情況。隨著未來幾個月醫學大會的通過，我們將看到更多數據。但我們希望透過像133這樣高效、便利的產品，帶來真正的效果改善。

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

我們的下一個問題來自美國銀行的傑夫·米查姆。

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 force?

Repatha 的變形已經有很長一段時間了。你們終於達到付款人的商業臨界點了嗎？或者您認為心臟科醫生的興趣越來越濃厚？我想，我不確定現在的市場怎麼樣，展望未來，影響如何？你們如何看待正在進行的第三階段和力量？

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，這是一段漫長的旅程，新冠病毒大流行並沒有幫助我們教育和說服心臟病專家，讓他們相信他們需要採取更多措施，更積極地治療患者的低密度脂蛋白膽固醇。我確實認為我們已經達到了心臟病學的轉折點，我確實認為我們已經達到了付款人的轉折點。我們現在已經涵蓋了90%以上的商業生活。

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.

我們預計能夠繼續擴大我們的 Medicare D 部分覆蓋範圍，我們看到 PCSK9 類別主要是由我們在該類別中所佔 80% 的份額推動的，現在真的真的開始發生變化。我們的新患者數量成長良好，不僅在美國，而且在世界各地。我們現在看到越來越多的初級保健醫生將 PCSK9 與其他藥物合併使用，以更積極地降低高風險 ASCVD 患者的 LDL。

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楚。付款人涵蓋範圍建立了患者的負擔能力，成熟的心臟病專家現在頻繁開處方，現在進入初級保健領域，我們將在這一組合中增加直接面向消費者的活動投資。所以，是的，我認為我們已經達到了 Repatha 的臨界點，Geoff，我看好我們可以採取哪些措施來進一步擴大該產品，無論是從銷售還是淨銷售額的角度來看。

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?

只是一個關於長期利潤率的問題。我想在地平線之後，我想，隨著你的管道的坡道，包括隨著時間的推移一些可能非常大的肥胖研究。我直接想，我們該如何考慮這裡的利潤？我想，這種 50% 或略高於 50% 的範圍是公司的合理目標，還是我們在平衡地平線與投資時應該牢記的任何考慮因素？

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.

好吧，克里斯，我們不會在這次電話會議上提供更新的保證金指導。但我認為我們已經非常清楚這條路應該是什麼樣子了。我們致力於維持業界領先高效的地位。隨著時間的推移，我們已經能夠實現領先的營業利潤率。我們在地平線業務中看到的任何具體情況都不需要我們得出與此不同的結論。

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，如果充分利用我們在國際上現有的基礎設施以及製造和製程開發，該業務的利潤將在我們手中具有吸引力。顯然，Peter 提到的研發支出較早，我們在這十年的中期進行了許多針對 Lp(a) 和肥胖產品的 III 期試驗。這可能會對整體利潤率產生影響，但我們將有足夠的時間提前討論這一點，這樣就不會有人對利潤率開始變化感到驚訝。因此，我們再次展示了管理業務成本結構的相當一致的能力，這是我們決心維持的能力。

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?

因此，前景的成長是相當可觀的。只是想知道如何將 10 億美元的運行率與您對交易的預期進行比較？然後退一步，我們在 JAMA 文章上看到使用 2 型糖尿病藥物治療痛風。您如何看待更廣泛的痛風領域？當談到 KRYSTEXXA 時，這是我們應該關心的事情嗎？

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.

也許我們會分成兩個部分。首先，關於 KRYSTEXXA，我想說 KRYSTEXXA 的表現非常好，我們相信它會的。同樣，我們認為這裡存在著巨大的未滿足的醫療需求，並且含有甲氨蝶呤的 KRYSTEXXA 正在很好地服務於市場。因此，我們期待與我們的同事就此展開合作。總的來說，我想說的是，到目前為止，業務正在按照我們的預期進行。我們認為掌握的東西很重要，例如 TEPEZZA 的慢性適應症，例如透過 OPTIC-J 試驗提供的國際數據集，例如我們在巴西取得的進展等等，這些是我們想要掌握並現在要做的事情。

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.

同樣，UPLIZNA 的表現也非常符合我們的預期。因此，我們在那裡看到了 3 個成長機會，我們看到了安進業務為 Vikram 現在在我們稀有業務領域運營的業務增加價值的方法。然後關於糖尿病的問題，我會問戴夫。

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很重要。這些患者患有嚴重且不受控制的痛風。例如，由於疾病的嚴重性，他們經常面臨截肢。因此，目前市場上有大量此類患者尚未在臨床實踐中得到服務。因此，我們的重點是接觸那些生活品質障礙相當嚴重的患者，且藥物在改善病程和改善生活品質方面的效果可能相當顯著。所以這就是現在的焦點。

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

我不會因為其他一些潛在的關聯而分心。

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，我認為這裡的日誌中還有 2 個呼叫。那麼，我們何不再拿兩個，然後我們會感謝我們的同事，讓他們繼續這一天。

Our next question comes from Tim Anderson from Wolfe Research.

我們的下一個問題來自沃爾夫研究中心的蒂姆·安德森。

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.

對於 AMG 133，也許這是一個愚蠢的問題，但有可能在 2024 年開始第三階段嗎？做到這一點的主要方法是在主要完成日期之前對第二階段試驗進行早期或臨時的觀察。我知道您正在為 24 年底的頂線提供指導。

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，當我們進入 24 年時，我們將就第三階段計劃何時啟動提供指導。按照這些計劃的慣例，我們將進行臨時審查。那將保持盲目。我們不會對外發布，因為這是一項為期 52 週的研究，但這至少有助於指導我們的思考。另請記住，在此處啟動 III 期試驗之前，FDA 需要一定的安全資料庫。因此，當我們進入明年並開始進行這些對話時，我們將能夠就何時可以啟動第三階段計劃以及該系列研究可能會是什麼樣子提供更明確的指導。

Our last question will come from Colin Bristow from UBS.

我們的最後一個問題將由瑞銀集團 (UBS) 的 Colin Bristow 提出。

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.

也許只是133的快速跟進。正如我們從商業角度思考這一點，這顯然是一個抗體骨幹。鑑於可實現的利潤，這將是一種注射劑。請幫助我們思考一下。

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.

好吧，科林，你已經指出這是抗體骨架。顯然，正如我之前提到的，其特性可能是您可以比市場上現有療法的頻率低得多。我們還認為，考慮到功效和可能的耐受性的潛在差異，我們將能夠在市場上為那些需要快速、深度和持續減肥的人們建立一個非常強大的地位，他們可以隨著時間的推移進行管理，從而獲得好處、心血管風險的降低、治療結果的改善。

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，我們希望透過一系列第三階段實驗來開發該產品，並且我們希望能夠佔據相當大的市場份額，這將為我們對該產品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.

我現在想將電話轉回給鮑勃·布拉德韋 (Bob Bradway)，讓他發表結束語。

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 few 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。好吧，讓我感謝大家今天早上加入我們，我們希望選擇早上這樣做是為了讓你們無論身在何處都能享受下午和晚上的“不給糖就搗蛋”遊戲。但我們再次感謝您的支持。在安進度過了多事的幾個月，我們期待著有機會與您重聚，並在新年到來時報告第四季度的情況。非常感謝。

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

我們的 2023 年第三季財報電話會議到此結束。您現在可以斷開連線。