美國安進 (AMGN) 2024 Q1 法說會逐字稿

My name is Julianne, and I will be your conference facilitator today for Amgen's First Quarter 2024 Financial Results Conference Call. (Operator Instructions)

我叫 Julianne，今天我將擔任安進 2024 年第一季財務業績電話會議的會議主持人。 （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 afternoon, and welcome to our first quarter 2024 earnings call. Bob Bradway will lead the call and be followed by a broader review of our performance by Jay Bradner, Murdo Gordon, Vikram Karnani and Peter Griffith.

謝謝你，茱麗安。下午好，歡迎參加我們的 2024 年第一季財報電話會議。鮑勃·布拉德威(Bob Bradway) 將主持電話會議，隨後傑·布拉德納(Jay Bradner)、默多·戈登(Murdo Gordon)、維克拉姆·卡納尼(Vikram Karnani) 和彼得·格里菲斯(Peter Griffith) 對我們的表現進行更廣泛的審查。

Through the course of our discussion today, we will use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompany this call. We will also make some forward-looking statements, which are qualified by our safe harbor statement. And please note that actual results can vary materially. Over to you, Bob.

在今天的討論過程中，我們將使用非公認會計準則財務指標來描述我們的業績，並在本次電話會議隨附的資料中提供適當的調節。我們也將做出一些前瞻性陳述，這些陳述符合我們的安全港聲明。請注意，實際結果可能會大不相同。交給你了，鮑伯。

Okay. Thank you, Justin, and thank you to our callers for joining us today. This is a busy and exciting time here at Amgen. And as you can see from our results, we're reaching many more patients around the world with our existing medicines, advancing a broad range of potential first-in-class medicines in our mid- and late-stage pipeline, and redefining what's possible in research as we integrate wet and dry lab capabilities and harness transformative technologies.

好的。謝謝賈斯汀，也謝謝我們今天加入我們的來電者。這是安進忙碌而激動人心的時刻。正如您從我們的結果中看到的，我們正在用我們現有的藥物接觸到世界各地更多的患者，在我們的中後期管道中推進一系列潛在的一流藥物，並重新定義可能性在研究中，我們整合了乾濕實驗室能力並利用變革性技術。

I'll touch on a few highlights from the quarter that give me great confidence that we're on a path to deliver attractive long-term growth. First, we have a number of products across general medicine, oncology and inflammation that have strong momentum and still plenty of room to grow. These include Repatha, which was up 33%; EVENITY, up 35%; BLINCYTO, up 26%; and TEZSPIRE, up 80%. With BLINCYTO, we expect an approval in June that should accelerate our efforts to integrate into earlier treatment lines for acute lymphoblastic leukemia.

我將談談本季的一些亮點，這些亮點讓我充滿信心，相信我們正在實現有吸引力的長期成長。首先，我們在普通醫學、腫瘤學和發炎領域擁有許多產品，這些產品勢頭強勁，仍有很大的成長空間。其中包括 Repatha，上漲 33%；均勻度，上漲 35%； BLINCYTO，上漲 26%；和TEZSPIRE，上漲80%。我們預計 BLINCYTO 將於 6 月獲得批准，這將加速我們整合到急性淋巴性白血病早期治療系列的努力。

With TEZSPIRE, we'll share data later this month that reflect the attractive potential of this medicine in chronic obstructive pulmonary disease. COPD is the world's third leading cause of death. Clearly, new treatments are very much needed, and we're excited by TEZSPIRE's potential to make a difference there.

我們將在本月稍後與 TEZSPIRE 分享數據，這些數據反映了該藥物在慢性阻塞性肺病方面的吸引力。慢性阻塞性肺病是世界第三大死因。顯然，我們非常需要新的治療方法，我們對 TEZSPIRE 在這方面發揮作用的潛力感到興奮。

Second, our newest pillar of growth, rare disease, contributed nearly $1 billion of sales in the quarter, up 14% compared with the sales of these products from a year ago. We see significant upside potential for first-in-class early-life cycle medicines like TEPEZZA, KRYSTEXXA, UPLIZNA and TAVNEOS. And we're pursuing launches in new geographic markets, new indications and/or new formulations for each. As an example, we announced last week our imminent plans to file TEPEZZA for approval in the European Union.

其次，我們最新的成長支柱——罕見疾病，在本季度貢獻了近 10 億美元的銷售額，與去年同期相比成長了 14%。我們看到 TEPEZZA、KRYSTEXXA、UPLIZNA 和 TAVNEOS 等一流的早期生命週期藥物具有巨大的上升潛力。我們正在尋求在新的地理市場、新的適應症和/或新的配方中推出產品。例如，我們上週宣布即將計劃向歐盟提交 TEPEZZA 申請批准。

Overall, the integration of Horizon, its people, products and pipeline is proceeding well, reflecting the strong fit between our organizations. Third, we are rapidly advancing a number of promising new medicines in our mid- and late-stage pipeline, spanning all 4 of our therapeutic areas. We are awaiting approval for tarlatamab, for example, and look forward to bringing this transformative innovation to patients with small cell lung cancer. Tarlatamab is the first T-cell-engaging therapy to demonstrate significant clinical activity against a common solid tumor, a watershed moment in a field that Amgen pioneered and continues to lead.

總體而言，Horizo​​​​n 及其人員、產品和通路的整合進展順利，反映了我們組織之間的緊密配合。第三，我們正在中後期管道中快速推進一些有前景的新藥，涵蓋我們的所有 4 個治療領域。例如，我們正在等待 tarlatamab 的批准，並期待將這項變革性創新帶給小細胞肺癌患者。 Tarlatamab 是第一個針對常見實體瘤表現出顯著臨床活性的 T 細胞參與療法，這是安進開創並繼續引領的領域的分水嶺。

Looking to the rest of the year, we anticipate data readouts from 5 Phase III trials. In addition, we announced today the development of a biosimilar to KEYTRUDA as we look to build upon the global leadership we have established in biosimilars.

展望今年剩餘時間，我們預計將公佈 5 項 III 期試驗的數據。此外，我們今天宣布開發 KEYTRUDA 生物相似藥，因為我們希望鞏固我們在生物相似藥領域建立的全球領導地位。

In sum, we have a broad range of medicines in hand today and coming through our pipeline that will enable us to meet the needs of millions of patients around the world and deliver strong growth through the end of the decade and beyond.

總而言之，我們現在擁有廣泛的藥物，並且正在透過我們的管道生產，這將使我們能夠滿足世界各地數百萬患者的需求，並在本世紀末及以後實現強勁增長。

Now let me just add one other important update. Whereas we don't normally comment on interim data, especially for our Phase II trial, we recognize there is significant interest in obesity in MariTide, so we'll provide additional commentary today. The interim Phase II analysis for this study is complete, and we are very encouraged with the results that we've seen thus far and with the conduct of the trial. Following the interim analysis, I would say we're confident in MariTide's differentiated profile and believe it will address important unmet medical needs.

現在讓我新增另一個重要更新。雖然我們通常不會對中期數據發表評論，特別是對於我們的 II 期試驗，但我們認識到人們對 MariTide 中的肥胖問題非常感興趣，因此我們今天將提供更多評論。這項研究的中期第二階段分析已經完成，我們對迄今為止所看到的結果以及試驗的進行感到非常鼓舞。根據中期分析，我想說，我們對 MariTide 的差異化形象充滿信心，並相信它將解決重要的未滿足的醫療需求。

We are actively planning a broad Phase III program including obesity, obesity-related conditions and diabetes. Obviously, we expect to carefully complete our ongoing Phase II trial before then moving as swiftly as appropriate to establish the safety and efficacy of this potential medicine in Phase III trials. We've initiated activities as well to further expand manufacturing capacity with both clinical and commercial supply in mind.

我們正在積極規劃一項廣泛的第三階段計劃，包括肥胖、肥胖相關疾病和糖尿病。顯然，我們希望仔細完成正在進行的二期試驗，然後儘快在三期試驗中確定這種潛在藥物的安全性和有效性。我們也啟動了進一步擴大生產能力的活動，同時考慮臨床和商業供應。

Jay will provide a few additional remarks with respect to this ongoing study. And I would ask you to recognize that to protect the integrity of the study beyond this update, we would not expect to discuss these data in further detail before completion. As always, I want to thank our employees around the world for their commitment to our business and to the patients we serve. Jay, I'll turn it over to you.

傑伊將就這項正在進行的研究提供一些補充評論。我想請您認識到，為了保護本次更新之後研究的完整性，我們不希望在完成之前進一步詳細討論這些數據。一如既往，我要感謝我們世界各地的員工對我們的業務和我們服務的患者的承諾。傑伊，我會把它交給你。

Thank you, Bob, and good afternoon, everyone. Let me start with MariTide. Reiterating Bob's comments, we are very pleased with the results seen with MariTide thus far. And we're very pleased with the overall conduct of the ongoing Phase II trial. All arms remain active, patient dropout has not been an issue, and we're fully on track for top line 52-week data from this 11-arm Phase II study in late 2024.

謝謝鮑勃，大家下午好。讓我從 MariTide 開始。重申 Bob 的評論，我們對 MariTide 迄今為止所取得的成果感到非常滿意。我們對正在進行的第二階段試驗的整體進行感到非常滿意。所有組別均保持活躍狀態，患者退出也不是問題，我們完全有望在 2024 年末獲得這項 11 組 II 期研究的 52 週頂線數據。

We're seeing a differentiated profile of MariTide and are confident that it will address important unmet medical needs, obesity, obesity-related conditions and diabetes. We look forward to completing the ongoing Phase II study and working with regulators to move rapidly to the broad Phase III program.

我們看到了 MariTide 的差異化形象，並相信它將解決重要的未滿足的醫療需求、肥胖、肥胖相關疾病和糖尿病。我們期待完成正在進行的第二階段研究，並與監管機構合作，迅速進入廣泛的第三階段計劃。

Later this year, we plan to initiate an additional dedicated Phase II trial investigating MariTide for the treatment of diabetes in patients with and without obesity. This new trial is not a gating step for our Phase III program in patients with obesity. Informed by dose and schedule insights from the ongoing Phase II obesity study, the dedicated Phase II study in diabetes conforms to regulatory requirements for Phase III and is the next step towards a diabetes indication for MariTide.

今年晚些時候，我們計劃啟動另一項專門的 II 期試驗，研究 MariTide 用於治療肥胖和非肥胖患者的糖尿病。這項新試驗並不是我們肥胖患者 III 期計畫的門檻步驟。根據正在進行的 II 期肥胖研究的劑量和時間表見解，專門針對糖尿病的 II 期研究符合 III 期的監管要求，是 MariTide 糖尿病適應症的下一步。

In terms of patient experience, we expect to deliver MariTide in a convenient, handheld, patient-friendly auto-injector device with a monthly or even less frequent single-injection administration, assuming eventual approval. Across the portfolio, we are presently prioritizing differentiated medicines, those that stand to provide the greatest benefit for patients. Given the profile we've seen with AMG 786, we will not pursue further development. Instead, in obesity, we're differentially investing in MariTide and a number of preclinical assets.

在患者體驗方面，我們預計以方便、手持、患者友善自動注射器設備的形式提供 MariTide，每月甚至更少頻率的單次注射（假設最終獲得批准）。在整個產品組合中，我們目前優先考慮差異化藥物，即那些能為患者提供最大利益的藥物。鑑於我們在 AMG 786 上看到的概況，我們不會尋求進一步的發展。相反，在肥胖方面，我們對 MariTide 和一些臨床前資產進行了差異化投資。

Beyond MariTide, in the first quarter, we rapidly advanced our diverse clinical pipeline of potentially first-in-class or best-in-class programs. Looking ahead, the remainder of 2024 promises to be an exciting time for research and development with 2 PDUFA dates in June for tarlatamab in small cell lung cancer and BLINCYTO in adult acute lymphoblastic leukemia as well as 5 Phase III data readouts. Each of these milestones could represent a significant advance towards our mission to deliver groundbreaking treatments to patients in real need.

除了 MariTide 之外，我們在第一季迅速推進了潛在一流或一流專案的多樣化臨床管道。展望未來，2024 年剩餘時間有望成為令人興奮的研發時刻，治療小細胞肺癌的 tarlatamab 和治療成人急性淋巴細胞白血病的 BLINCYTO 的 2 個 PDUFA 日期將於 6 月發布，以及 5 個 III 期數據讀出。這些里程碑中的每一個都代表著我們為真正有需要的患者提供突破性治療的使命的重大進步。

Moving to olpasiran. We're pleased to announce that we've completed enrollment of the OCEAN(a)-Outcomes trial, a Phase III cardiovascular outcome study of olpasiran, our potentially best-in-class Lp(a)-targeting small interfering RNA medicine. Reflecting both our commitment to patients suffering from cardiovascular disease and the strong interest of the medical community, we successfully enrolled 7,297 patients across the globe in just 15.5 months. To our knowledge, this is the fastest-enrolling Phase III outcome study of its size. And to remind, Lp(a) is a genetically defined cardiovascular risk factor, which is elevated in approximately 20% of individuals and for whom no effective or targeted therapies currently exist.

搬到奧爾帕西蘭。我們很高興地宣布，我們已經完成了OCEAN(a)-Outcomes 試驗的招募，這是一項olpasiran 的III 期心血管結果研究，olpasiran 是我們潛在的同類最佳Lp(a) 靶向小幹擾RNA藥物。我們在短短 15.5 個月內成功招募了全球 7,297 名患者，這不僅體現了我們對心血管疾病患者的承諾，也體現了醫學界的強烈興趣。據我們所知，這是同類規模中招募速度最快的 III 期結果研究。需要提醒的是，Lp(a) 是一種基因定義的心血管危險因素，約 20% 的個體的 Lp(a) 升高，且目前尚無有效或標靶治療方法。

In oncology, we continue to deliver on high-conviction targets with differentiated therapies capable of delivering a large effect size for patients. Starting with tarlatamab, a first-in-class BiTE molecule targeting DLL3 for small cell lung cancer. We remain on track with an FDA priority review for a June 12 PDUFA date.

在腫瘤學領域，我們繼續透過能夠為患者帶來巨大療效的差異化療法來實現高度確信的目標。從 tarlatamab 開始，這是一種針對小細胞肺癌的首創 BiTE 分子，可針對 DLL3。我們仍在按計劃於 6 月 12 日 PDUFA 日期進行 FDA 優先審查。

We're excited about tarlatamab as potentially the first selective therapy for small cell lung cancer. Based on the remarkable activity observed as a single agent in patients receiving second and third-line therapy, we are rapidly advancing tarlatamab in a frontline treatment with 3 Phase III studies now initiated in both extensive stage and limited stage disease.

我們對 tarlatamab 可能成為小細胞肺癌的第一個選擇性療法感到興奮。基於在接受二線和三線治療的患者中觀察到的單藥顯著活性，我們正在快速推進 tarlatamab 在一線治療中的應用，目前已在廣泛期和有限期疾病中啟動了 3 項 III 期研究。

The rationale for studying tarlatamab in earlier lines of the context of lower tumor burden draws from our experience with BLINCYTO in B-cell ALL. There, we saw a dramatic improvement in overall survival in minimal residual disease-negative patients. These BLINCYTO data provide evidence that directing the T-cell in this manner is an effective means of finding and eliminating residual cancer cells, which are primarily the drivers of recurrent disease. We're hopeful we can build on this insight with tarlatamab, where comparable activity in early-stage small cell lung cancer patients would very meaningfully improve outcomes for patients facing the challenge of this aggressive cancer.

在較低腫瘤負荷背景下早期研究 tarlatamab 的基本原理源自於我們在 B 細胞 ALL 中使用 BLINCYTO 的經驗。在那裡，我們看到微小殘留疾病陰性患者的總存活率顯著提高。這些 BLINCYTO 數據提供的證據表明，以這種方式引導 T 細胞是發現和消除殘留癌細胞的有效方法，而殘留癌細胞是疾病復發的主要驅動因素。我們希望我們能夠在 tarlatamab 的基礎上進一步發展，在早期小細胞肺癌患者中進行類似的活動將非常有意義地改善面臨這種侵襲性癌症挑戰的患者的預後。

In sum, we regard tarlatamab as a major advance as the first bispecific T-cell engager to demonstrate efficacy in a common solid tumor, further establishing the broad potential of our bispecific T-cell engager platform. Our first-in-class STEAP1 CD3 bispecific molecule, xaluritamig, has also demonstrated unambiguous activity in the solid tumor, namely prostate cancer, continues to advance following a presentation of encouraging Phase I data last fall. We have now fully enrolled the monotherapy Phase I dose expansion and continue to enroll patients in reduced monitoring and outpatient cohorts. Further, combination studies with xaluritamig in novel hormonal therapies are progressing in dose escalation studies with near-term plans to initiate dose expansion cohorts.

總之，我們認為 tarlatamab 作為第一個在常見實體瘤中展示療效的雙特異性 T 細胞接合劑是一項重大進展，進一步確立了我們的雙特異性 T 細胞接合劑平台的廣泛潛力。我們一流的 STEAP1 CD3 雙特異性分子 xaluritamig 在實體瘤（即前列腺癌）中也表現出明確的活性，繼去年秋天提供令人鼓舞的 I 期數據後，該藥物繼續取得進展。我們現在已全面招募單藥治療 I 期劑量擴展，並繼續將患者納入減少監測和門診隊列。此外，新型荷爾蒙療法中卡魯他米的聯合研究正在劑量遞增研究中取得進展，近期計劃啟動劑量擴展隊列。

To round out oncology, we are rapidly advancing AMG 193, our oral PRMT5 inhibitor targeting MTAP null solid tumors. We've moved forward with monotherapy dose expansion studies and have initiated 2 additional Phase I studies targeting MTAP null tumors in thoracic, gastrointestinal, biliary tract and pancreatic cancers, exploring relevant combinations with standard of care.

為了完善腫瘤學，我們正在快速推進 AMG 193，這是我們針對 MTAP 無效實體瘤的口服 PRMT5 抑制劑。我們已經推進了單一療法劑量擴展研究，並啟動了另外兩項針對胸部、胃腸道、膽道和胰腺癌中 MTAP 無效腫瘤的 I 期研究，探索與標準護理的相關組合。

In our inflammation portfolio, we are encouraged by the results of the COURSE Phase IIa proof-of-concept study, which investigated TEZSPIRE in patients with moderate to very severe COPD. This study was designed to test TSLP inhibition across an intentionally broad range of eosinophil levels, irrespective of inflammatory drivers, emphysema, chronic bronchitis and smoking status. While TEZSPIRE achieved a clinically meaningful 17% reduction in the annualized rate of moderate or severe COPD exacerbations compared to placebo, this result fell short of statistical significance likely owing to the broad overall patient demographic.

在我們的發炎產品組合中，我們對 COURSE IIa 期概念驗證研究的結果感到鼓舞，該研究調查了 TEZSPIRE 對中度至極重度 COPD 患者的作用。本研究旨在測試廣泛範圍的嗜酸性粒細胞水平的 TSLP 抑製作用，無論發炎驅動因素、肺氣腫、慢性支氣管炎和吸煙狀況如何。雖然與安慰劑相比，TEZSPIRE 使中度或重度 COPD 惡化的年化發生率降低了 17%，具有臨床意義，但這一結果未能達到統計顯著性，可能是由於總體患者人口統計廣泛。

However, even greater reductions in COPD exacerbations were observed in a planned subgroup of patients with baseline blood eosinophil counts greater than 150 cells per microliter with a trend for further reduction in a small number of subjects with baseline counts greater than 300. We're excited by these data, which will be presented in an oral session of the American Thoracic Society Annual Meeting later this month.

然而，在基線血液嗜酸性粒細胞計數大於150 個細胞/微升的計劃亞組患者中觀察到COPD 急性加重的減少幅度更大，且基線計數大於300 的少數受試者有進一步減少的趨勢。我們很興奮這些數據將於本月稍晚在美國胸腔科學會年會的口頭會議上公佈。

Together with our partner, AstraZeneca, we are actively planning for Phase III development of TEZSPIRE in COPD. Beyond COPD, we continue to explore TEZSPIRE in separate Phase III studies in eosinophilic esophagitis and chronic rhinosinusitis with nasal polyps, where top line data are expected in the second half of this year.

我們與我們的合作夥伴阿斯特捷利康一起，積極規劃 TEZSPIRE 治療慢性阻塞性肺病的 III 期開發。除了慢性阻塞性肺病之外，我們還在嗜酸性粒細胞性食道炎和伴有鼻息肉的慢性鼻竇炎的單獨 III 期研究中繼續探索 TEZSPIRE，預計將在今年下半年獲得一線數據。

The ROCKET Phase III program for rocatinlimab, a first-in-class anti-OX40 monoclonal antibody, has successfully enrolled over 2,800 patients with moderate to severe atopic dermatitis. Indeed, 3 of the 8 studies in the rocatinlimab ROCKET study program are now fully enrolled. The Phase III Horizon study, part of this ROCKET program, evaluates rocatinlimab monotherapy versus placebo in adults with moderate to severe atopic dermatitis and remains on track for top line data readout in the second half of this year.

rocatinlimab（一種一流的抗 OX40 單株抗體）的 ROCKET III 期計畫已成功入組 2,800 多名中重度異位性皮膚炎患者。事實上，rocatinlimab ROCKET 研究計畫的 8 項研究中的 3 項現已全部入組。 III 期 Horizo​​n 研究是 ROCKET 計劃的一部分，該研究評估了 rocatinlimab 單藥治療與安慰劑治療中度至重度異位性皮膚炎成人的療效，並預計在今年下半年公佈頂線數據。

Beyond atopic dermatitis, we continue to broadly explore rocatinlimab in additional indications and have initiated a Phase II study in moderate to severe asthma with plans to initiate a Phase III study in prurigo nodularis in the second half of this year. We're encouraged by the advancements of our rare disease pipeline as well with several mid- to late-stage opportunities.

除了異位性皮膚炎之外，我們繼續廣泛探索 rocatinlimab 的其他適應症，並已啟動中度至重度氣喘的 II 期研究，併計劃在今年下半年啟動結節性癢疹的 III 期研究。我們對罕見疾病產品線的進步以及一些中後期機會感到鼓舞。

Starting with UPLIZNA, we anticipate important Phase III data readouts this year in myasthenia gravis and IgG4-related disease, both diseases with significant unmet need and where we have the potential to make a real difference for patients.

從 UPLIZNA 開始，我們預計今年將公佈重症肌無力和 IgG4 相關疾病的重要 III 期數據，這兩種疾病的需求顯著未得到滿足，而且我們有潛力為患者帶來真正的改變。

Dazodalibep, an innovative CD40 ligand inhibitor fusion protein, has entered Phase III for Sjogren's disease with 2 studies now enrolling patients. This follows encouraging Phase II data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden. Dazodalibep is the first therapy to demonstrate efficacy in the latter patient population.

Dazodalibep 是一種創新的 CD40 配體抑制劑融合蛋白，已進入乾燥症的 III 期臨床研究，目前有 2 項研究正在招募患者。在此先前的第二階段數據令人鼓舞，該數據對中度至重度全身性疾病患者和高症狀負擔患者有效。 Dazodalibep 是第一個在後者患者群體中顯示出療效的療法。

Lastly, in our biosimilars portfolio, we've initiated a Phase III study of ABP 234, a biosimilar candidate to KEYTRUDA, in subjects with advanced or metastatic non-squamous non-small cell lung cancer. We're also pleased to announce that WEZLANA, our biosimilar candidate to STELARA, has received a positive CHMP opinion.

最後，在我們的生物相似藥組合中，我們啟動了 ABP 234（KEYTRUDA 的生物相似藥候選藥物）在晚期或轉移性非鱗狀非小細胞肺癌受試者中的 III 期研究。我們也很高興地宣布，STELARA 的候選生物仿製藥 WEZLANA 已收到 CHMP 的積極意見。

In closing, I'd like to thank my Amgen colleagues for their strong sense of service to patients facing serious illness and their commitment to growing the impact of both our research and our business to our portfolio of potential first-in-class and best-in-class medicines. And I'll now turn it over to Murdo.

最後，我要感謝我的安進同事為面臨嚴重疾病的患者提供強烈的服務意識，並致力於擴大我們的研究和業務對我們潛在的一流和最佳產品組合的影響。現在我將把它交給默多。

Thanks, Jay. I'm pleased with our performance in the first quarter. Strong execution resulted in sales growth of 22% year-over-year, with robust volume growth across the 4 therapeutic pillars of our business. We drove compelling growth across our regions with 10 products delivering at least double-digit volume growth, including Repatha, EVENITY, TEZSPIRE, TAVNEOS and BLINCYTO. Our integration of the legacy Horizon business continues to progress well with that portfolio generating $914 million in the quarter.

謝謝，傑伊。我對我們第一季的表現感到滿意。強大的執行力導致銷售額年增 22%，我們業務的 4 個治療支柱的銷售量也實現了強勁增長。我們透過 10 種產品實現了至少兩位數的銷售成長，推動了各地區的引人注目的成長，其中包括 Repatha、EVENITY、TEZSPIRE、TAVNEOS 和 BLINCYTO。我們對傳統 Horizo​​n 業務的整合繼續進展順利，該投資組合在本季度創造了 9.14 億美元的收入。

Sales in our general medicines business, including Repatha, Prolia, EVENITY and Aimovig grew 18% year-over-year in the first quarter, driven by volume growth. Repatha sales increased 33% year-over-year to a record of $517 million for the first quarter, and Repatha is now well on its way to becoming a multibillion-dollar business. In the quarter, we saw year-over-year volume growth of 44%, partially offset with 13% lower net selling price.

在銷售成長的推動下，我們的普通藥品業務（包括 Repatha、Prolia、EVENITY 和 Aimovig）的銷售額第一季同比增長 18%。 Repatha 在第一季銷售額年增 33%，達到創紀錄的 5.17 億美元，目前 Repatha 正成為一家價值數十億美元的企業。本季度，銷量年增 44%，但淨售價下降 13%，部分抵銷了這一成長。

Expanded formulary coverage for Repatha in the U.S. has accelerated volume growth. This was partially offset by lower net selling price resulting from higher rebates to support and expand access for patients. We expect this expanded formulary coverage, along with the removal of prior authorization requirements by several payers, will lead to increased cardiologist and primary care physician adoption.

Repatha 在美國的處方覆蓋範圍擴大加速了銷售成長。這部分抵消，因為為支持和擴大患者就診而提供的回扣較高，導致淨售價較低。我們預計，擴大處方覆蓋範圍，以及取消多個付款人的事先授權要求，將導致心臟病專家和初級保健醫生的採用增加。

Outside the U.S., we also delivered strong growth, helping even more patients reduce their cardiovascular risk. EVENITY had record sales of $342 million for the quarter. And in the U.S., volume growth was supported by an expansion of EVENITY prescribers. In Japan, EVENITY continues to be the segment leader with 46% of the bone builder market. And while we're happy with the growth of EVENITY, there are many women who remain at risk of a fracture due to their postmenopausal osteoporosis. And we see exciting growth potential for EVENITY to combat this risk, and we'll continue to apply our proven experience in bone health to ensure EVENITY reaches all the patients who need it.

在美國以外，我們也實現了強勁成長，幫助更多患者降低心血管風險。 EVENITY 本季銷售額達到創紀錄的 3.42 億美元。在美國，EVENITY 處方人數的增加推動了銷售量的成長。在日本，EVENITY 繼續佔據該細分市場的領導者地位，佔據造骨劑市場 46% 的份額。雖然我們對 EVENITY 的發展感到高興，但仍有許多女性因停經後骨質疏鬆症而面臨骨折的風險。我們看到 EVENITY 具有令人興奮的成長潛力來應對這一風險，我們將繼續運用我們在骨骼健康方面經過驗證的經驗，確保 EVENITY 惠及所有需要它的患者。

Prolia sales grew 8% year-over-year. Volume growth continues to be supported by real-world evidence, reaffirming Prolia's superiority in reducing fracture risk when compared to alendronate in treatment-naive patients with postmenopausal osteoporosis, who are at high risk of fracture.

Prolia 銷售額較去年同期成長 8%。體積增長繼續得到現實世界證據的支持，再次證實了對於骨折風險較高的停經後骨質疏鬆症初治患者，與阿崙膦酸鈉相比，Prolia 在降低骨折風險方面具有優越性。

In our inflammation business, Otezla sales increased 1% year-over-year for the first quarter. In the U.S., we saw strong new patient volume growth early in the quarter. This was disrupted in February and March by the Change Healthcare cybersecurity issue, which created challenges for some patients trying to fill prescriptions at specialty pharmacies.

在我們的發炎業務中，Otezla 第一季銷售額年增 1%。在美國，我們在本季初看到新患者數量強勁成長。這一情況在二月和三月因 Change Healthcare 網路安全問題而中斷，這給一些試圖在專業藥房配藥的患者帶來了挑戰。

We've seen a return to accelerating new patient prescription growth in recent weeks. We see significant potential for future growth of Otezla, given its established efficacy and safety profile, excellent payer coverage with limited prior authorization requirements and, of course, ease of administration. To realize this potential, we've increased our investment in dermatology field force and Otezla direct-to-consumer media, focusing on efforts to educate physicians and patients on the importance of treating psoriasis systemically and the safety and efficacy profile of Otezla.

最近幾週，我們看到新患者處方成長加速。鑑於 Otezla 既定的功效和安全性、良好的付款人覆蓋範圍以及有限的事先授權要求，當然還有易於管理的特點，我們認為 Otezla 未來的成長潛力巨大。為了實現這一潛力，我們增加了對皮膚科現場力量和 Otezla 直接面向消費者的媒體的投資，重點是教育醫生和患者係統治療牛皮癬的重要性以及 Otezla 的安全性和有效性。

I'm also pleased that Otezla was recently granted pediatric exclusivity and approved by the FDA for the treatment of pediatric patients 6 years of age and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. This is the first pediatric indication for Otezla.

我還很高興 Otezla 最近獲得了兒科獨家授權，並獲得 FDA 批准用於治療 6 歲及以上患有中度至重度斑塊型銀屑病且適合光療或全身治療的兒科患者。這是 Otezla 的第一個兒科適應症。

Enbrel sales decreased 2% year-over-year for the first quarter, driven by volume decline, partially offset by higher inventory levels. Moving forward, we expect modest volume growth offset by declining net selling price. TEZSPIRE continues its strong trajectory with $173 million in sales in the first quarter. Sales increased 80% year-over-year, primarily driven by uptake of the prefilled single-use pen.

由於銷量下降，Enbrel 第一季銷售額同比下降 2%，但庫存水準上升部分抵消了這一影響。展望未來，我們預期銷量的溫和成長將被淨售價下降所抵銷。 TEZSPIRE 持續保持強勁勢頭，第一季銷售額達 1.73 億美元。銷售額年增 80%，這主要是由預裝一次性筆的使用所推動的。

In our rare disease business, sales of TAVNEOS were $51 million in the first quarter. Sales increased 122% year-over-year, driven by volume growth. In the U.S., more than 3,000 patients have now been treated with TAVNEOS by over 2,000 health care professionals. Looking forward, we'll continue to leverage our expertise in nephrology and inflammation to bring TAVNEOS to even more patients with ANCA-associated vasculitis.

在我們的罕見疾病業務中，TAVNEOS 第一季的銷售額為 5,100 萬美元。在銷量成長的推動下，銷售額較去年同期成長 122%。在美國，超過 3,000 名患者現已接受了 2,000 多名醫療保健專業人員的 TAVNEOS 治療。展望未來，我們將繼續利用我們在腎臟病學和發炎方面的專業知識，將 TAVNEOS 帶給更多 ANCA 相關血管炎患者。

Sales for our biosimilars portfolio grew 12% year-over-year for the first quarter, with volume growth partially offset by lower inventory levels and net selling price decline. We expect continued growth in our biosimilars business to be driven by the addition of new molecules and additional launches.

第一季我們的生物相似藥組合銷售額年增 12%，銷售成長部分被庫存水準下降和淨售價下降所抵銷。我們預計我們的生物相似藥業務的持續成長將由新分子的添加和更多產品的推出推動。

In oncology, sales of our 6 innovative products, BLINCYTO, LUMAKRAS, Vectibix, KYPROLIS, Nplate and XGEVA, grew 4% year-over-year for the first quarter, driven by volume growth. BLINCYTO sales grew 26% year-over-year to a record $244 million for the first quarter, driven by broad prescribing across academic and community segments for patients with B-cell precursor acute lymphoblastic leukemia. The U.S. Food and Drug Administration has set a PDUFA date of June 21 of this year for its decision on approving BLINCYTO as a treatment for patients with early-stage CD19-positive, B-cell ALL. We see significant growth potential for BLINCYTO from utilization in frontline treatment.

在腫瘤學領域，在銷售成長的推動下，我們的 6 種創新產品 BLINCYTO、LUMAKRAS、Vectibix、KYPROLIS、Nplate 和 XGEVA 第一季的銷售額年增 4%。在學術界和社區領域針對 B 細胞前體急性淋巴性白血病患者的廣泛處方的推動下，BLINCYTO 第一季銷售額年增 26%，達到創紀錄的 2.44 億美元。美國食品藥物管理局已將 PDUFA 日期定為今年 6 月 21 日，以決定批准 BLINCYTO 用於治療早期 CD19 陽性 B 細胞 ALL 患者。我們看到 BLINCYTO 在第一線治療中的應用具有巨大的成長潛力。

LUMAKRAS sales increased 11% year-over-year for the first quarter to a record $82 million. We see future growth opportunities for LUMAKRAS coming from the launches in new markets and additional indications. Vectibix sales increased 6% year-over-year, driven by higher net selling price and volume growth, partially offset by unfavorable foreign exchange impact. KYPROLIS sales grew 5% year-over-year to a record $376 million for the first quarter, primarily driven by volume growth outside the U.S. Nplate sales decreased 12% year-over-year for the first quarter, primarily driven by volume decline in comparison to the first quarter of 2023, which included a U.S. government order of $82 million. Excluding the Q1 2023 U.S. government order, Nplate sales grew 13% year-over-year.

LUMAKRAS 第一季銷售額年增 11%，達到創紀錄的 8,200 萬美元。我們認為 LUMAKRAS 未來的成長機會來自於新市場的推出和其他適應症。在淨售價和銷售成長的推動下，Vectibix 銷售額年增 6%，但部分被不利的外匯影響所抵銷。 KYPROLIS 第一季銷售額年增 5%，達到創紀錄的 3.76 億美元，主要受到美國以外地區銷售成長的推動。第一季度，其中包括美國政府的8,200 萬美元訂單。不計2023年第一季美國政府訂單，Nplate銷售額年增13%。

I'm pleased with our execution in the quarter and the momentum across the 4 pillars of our business. And we look forward to serving many more patients around the world who can benefit from our innovative therapies. And with that, I'll turn it over to Vikram.

我對本季度的執行情況以及我們業務四大支柱的勢頭感到滿意。我們期待為世界各地更多可以從我們的創新療法中受益的患者提供服務。有了這個，我會把它交給維克拉姆。

Thank you, Murdo. I am pleased to provide an update on rare disease, Amgen's fourth therapeutic pillar of growth, which delivered product sales of over $950 million in Q1. Beginning with TEPEZZA for the treatment of thyroid eye disease, or TED, first quarter sales were $424 million, reflecting growth of 5% year-over-year when compared to results from the legacy Horizon business.

謝謝你，默多。我很高興提供有關罕見疾病的最新信息，這是安進第四個治療增長支柱，第一季的產品銷售額超過 9.5 億美元。從用於治療甲狀腺眼疾（TED）的 TEPEZZA 開始，第一季銷售額為 4.24 億美元，與傳統 Horizo​​n 業務的業績相比，年成長 5%。

As we discussed at our rare disease investor meeting a few months back, TED is often assessed using the clinical activity score, or CAS, which covers a number of different signs and symptoms, including pain, redness, swelling and function. And we now refer to TED in terms of high and low clinical activity score or high and low CAS. For the approximately 100,000 TED patients in the U.S. who could benefit from TEPEZZA, the majority of these patients, roughly 80%, are in low CAS settings. We continue to focus on this large number of low CAS patients not being appropriately treated.

正如我們在幾個月前的罕見疾病投資者會議上討論的那樣，TED 通常使用臨床活動評分 (CAS) 進行評估，該評分涵蓋許多不同的體徵和症狀，包括疼痛、發紅、腫脹和功能。我們現在用臨床活動評分的高低或 CAS 的高低來指稱 TED。對於美國約 10 萬名可以從 TEPEZZA 受益的 TED 患者來說，其中大多數患者（約 80%）處於低 CAS 環境中。我們繼續關注大量未適當治療的低 CAS 患者。

As we previously discussed, one of the main hurdles in the patient journey in this setting is access. To help patients overcome that challenge, we have generated favorable medical policy changes for greater than 50% of U.S. covered lives, and we expect to continue this momentum throughout 2024.

正如我們之前討論的，在這種情況下患者旅程的主要障礙之一是訪問。為了幫助患者克服這項挑戰，我們為超過 50% 的美國受保人口制定了有利的醫療政策，我們預計將在 2024 年繼續保持這一勢頭。

In addition, we are expanding our reach among new prescribers, particularly ophthalmologists and endocrinologists who manage many low CAS patients. The impact of TED on quality of life is often underestimated. So our focus is on educating health care providers about the significant effects on patients, even those with less visible symptoms. In addition to our focus on educating ocular surgeons and ophthalmologists, we are increasing our strategic focus in endocrinology and creating a dedicated sales force to engage in this important space.

此外，我們正在擴大新處方醫生的影響範圍，特別是管理許多低 CAS 患者的眼科醫生和內分泌科醫生。 TED 對生活品質的影響常被低估。因此，我們的重點是教育醫療保健提供者了解對患者的重大影響，即使是那些症狀不太明顯的患者。除了專注於教育眼外科醫生和眼科醫生外，我們還加強了內分泌學方面的戰略重點，並組建了一支專門的銷售團隊來參與這一重要領域。

International expansion remains a meaningful long-term growth opportunity for TEPEZZA, which is currently approved in Brazil and Saudi Arabia. As a reminder, in January, we filed for high CAS approval in Japan. And our Phase III trial in low CAS is continuing to enroll. We have completed additional regulatory submissions in Australia, Canada, Great Britain and most recently with the European Medicines Agency. We initiated a Phase III subcutaneous study and see this as an opportunity to increase adoption and improve the patient experience with an alternative option to our current IV formulation.

國際擴張對於 TEPEZZA 來說仍然是一個有意義的長期成長機會，目前該產品已在巴西和沙烏地阿拉伯獲得批准。提醒一下，一月份，我們在日本申請了 CAS 的高批准。我們在低 CAS 中的 III 期試驗正在繼續招募。我們已在澳洲、加拿大、英國以及最近與歐洲藥品管理局完成了額外的監管提交。我們啟動了一項 III 期皮下研究，並認為這是一個機會，可以透過我們目前 IV 製劑的替代方案來增加採用率並改善患者體驗。

KRYSTEXXA, for patients with chronic refractory gout, delivered $235 million in sales in Q1, representing 26% year-over-year growth, driven by volume growth from strong commercial execution. UPLIZNA, the fastest-growing biologic in NMOSD, delivered a record $80 million in net sales in Q1, representing 49% year-over-year growth. International expansion is also underway with UPLIZNA now launched in multiple ex-U.S. markets including Canada, which launched in January of this year.

KRYSTEXXA 是針對慢性難治性痛風患者的藥物，在強勁的商業執行力推動銷量成長的推動下，第一季銷售額達 2.35 億美元，年成長 26%。 UPLIZNA 是 NMOSD 中成長最快的生物製劑，第一季淨銷售額達到創紀錄的 8,000 萬美元，年增 49%。國際擴張也正在進行中，UPLIZNA 現已在美國以外的多個國家推出。市場包括加拿大，於今年一月推出。

The integration of the legacy Horizon business continues to be on track as we leverage Amgen's leadership in inflammation, world-class manufacturing and process development and extensive global footprint. Now I will pass it over to Peter for our financial update.

隨著我們利用安進在發炎領域的領導地位、世界一流的製造和工藝開發以及廣泛的全球足跡，原有 Horizo​​n 業務的整合繼續順利進行。現在我將把它轉交給彼得，以獲取我們的最新財務資訊。

Thank you, Vikram. We're pleased with our performance and on track to meet our 2024 full goals and long-term objectives. Our strong growth outlook is driven across each of our 4 therapeutic pillars by our innovative pipeline and in-market portfolio products, which serve patients with serious illnesses around the globe. I'll review our first quarter results before discussing our 2024 guidance.

謝謝你，維克拉姆。我們對自己的表現感到滿意，並有望實現 2024 年的全部目標和長期目標。我們強勁的成長前景是由我們的創新管道和市場產品組合推動的，這些產品為全球患有嚴重疾病的患者提供服務。 。在討論我們的 2024 年指導之前，我將回顧我們第一季的業績。

As shown on Slide 23 of the slide deck, in the first quarter, we delivered $7.4 billion in total revenue, a 22% increase year-over-year. This reflects 25% volume growth, including over $900 million from acquired Horizon products and also key brands, including Repatha, TEZSPIRE, EVENITY, Prolia and BLINCYTO. Excluding the addition of Horizon, product sales increased 6% year-over-year, driven by 9% volume growth.

如投影片第 23 幅所示，第一季我們實現了 74 億美元的總收入，年增 22%。這反映了 25% 的銷售成長，其中包括收購的 Horizo​​n 產品和主要品牌（包括 Repatha、TEZSPIRE、EVENITY、Prolia 和 BLINCYTO）帶來的超過 9 億美元的銷售額。不包括 Horizo​​n 的加入，在銷售成長 9% 的推動下，產品銷售額年增 6%。

Our non-GAAP operating expenses rose by 33%, reflecting investments in Horizon acquired products, along with other late-stage pipeline medicines, including rocatinlimab, MariTide and tarlatamab. As a result, our Q1 operating margin was 43%, consistent with our guidance on the fourth quarter earnings call. Our non-GAAP OI&E resulted in $549 million expense, up $334 million year-over-year, almost entirely due to increased interest expense from debt issued for the Horizon acquisition, partially offset by higher interest income and gains from debt repurchases.

我們的非 GAAP 營運費用增加了 33%，反映了對 Horizo​​​​n 收購的產品以及其他後期管道藥物（包括 rocatinlimab、MariTide 和 tarlatamab）的投資。因此，我們第一季的營業利潤率為 43%，與我們對第四季財報電話會議的指導一致。我們的非 GAAP OI&E 支出為 5.49 億美元，年增 3.34 億美元，幾乎完全是由於 Horizo​​n 收購而發行的債務利息支出增加，部分被更高的利息收入和債務回購收益所抵消。

Our non-GAAP tax rate decreased 2.4 percentage points year-over-year to 15.4%, primarily due to the change in earnings mix, the inclusion of the Horizon business, and net favorable items in the quarter. In the first quarter, the company generated $0.5 billion in free cash flow, a decrease from $0.7 billion in the previous year, primarily impacted by a planned $800 million tax deposit to the IRS to stop the accrual of interest on uncertain tax positions, as we discussed on our fourth quarter earnings call.

我們的非 GAAP 稅率年減 2.4 個百分點至 15.4%，這主要是由於盈利組合的變化、Horizo​​​​n 業務的納入以及本季度的淨優惠項目。第一季度，該公司產生了5 億美元的自由現金流，比前一年的7 億美元有所減少，這主要是受到計劃向國稅局繳納8 億美元的稅款存款的影響，以阻止不確定的稅務狀況應計利息，因為我們我們在第四季度財報電話會議上進行了討論。

As a reminder, there is no change in our belief in the merits of our legal position as we prepare for trial later this year. This impact on free cash flow was partially offset by the timing of working capital items. The Horizon integration is on track, and we expect to reach our pretax $500 million synergy target by year 3 post acquisition. We also expect to achieve roughly 50% of this synergy target in our annual run rate by the end of this year 2024. We expect accretion to non-GAAP EPS in 2024 and anticipate maintaining strong cash flow generation while we continue to execute on our deleveraging plan to return to our pre-acquisition efficient capital structure by the end of 2025.

提醒一下，在我們為今年稍後的審判做準備時，我們對我們法律立場優點的信念沒有改變。對自由現金流的影響被營運資本項目的時間安排部分抵銷。 Horizo​​n 整合已步入正軌，我們預計在收購後第 3 年實現稅前 5 億美元的協同目標。我們也預計到2024 年年底，我們的年度運行率將實現這一協同目標的大約50%。強勁的現金流量產生計劃在 2025 年底恢復收購前的高效資本結構。

We remain on track to achieve the pre-acquisition leverage ratio, normalized for certain other noncash items, including fair value, market value adjustment of equity investments and Horizon acquisition-related costs. We remain committed to our multiple capital allocation priorities. We continue to prioritize investing in the best innovation, both internally and externally, with increased spending on late-stage programs, including olpasiran, bemarituzumab, MariTide and rocatinlimab.

我們仍有望實現收購前的槓桿率，並對某些其他非現金項目進行標準化，包括公允價值、股權投資的市場價值調整和 Horizo​​​​n 收購相關成本。我們仍然致力於多種資本配置優先事項。我們繼續優先投資於內部和外部的最佳創新，增加後期項目的支出，包括 olpasiran、bemarituzumab、MariTide 和 rocatinlimab。

Second, we continue investing in our business for long-term growth, including expanding capacity in our state-of-the-art manufacturing facilities. Our North Carolina site is expected to be operational by 2026. And Amgen Ohio opened in the first quarter and is utilizing artificial intelligence and extensive robotics to boost operational efficiencies.

其次，我們繼續投資我們的業務以實現長期成長，包括擴大我們最先進的製造設施的產能。我們的北卡羅來納工廠預計將於 2026 年投入營運。

We're actively integrating generative AI across the enterprise to spearhead innovation and reinforce our leadership in the industry. This strategic commitment to innovative technology enables us to lead advancements, streamline drug development and enhance patient care more effectively.

我們正在積極地將生成式人工智慧整合到整個企業中，以引領創新並鞏固我們在產業中的領導地位。這種對創新技術的策略承諾使我們能夠引領進步、簡化藥物開發並更有效地加強患者護理。

Finally, we returned capital to shareholders as we paid dividends of $2.25 per share in the first quarter. This represented a 6% increase over that paid in each of 2023's 4 quarters.

最後，我們將資本返還給股東，第一季支付了每股 2.25 美元的股息。這比 2023 年 4 個季度每季的支付額增加了 6%。

Turning to the outlook for the business for 2024 on Slide 25. We expect our 2024 total revenues in the range of $32.5 billion to $33.8 billion and anticipate non-GAAP earnings per share between $19 and $20.20. I'll mention a few considerations as you model the remainder of 2024. Our non-GAAP R&D expenses are expected to increase by approximately 25% year-over-year versus our prior guidance to you roughly 20% year-over-year. We're making incremental investments based on our confidence in our late-stage pipeline.

轉向幻燈片 25 上的 2024 年業務前景。當您對 2024 年剩餘時間進行建模時，我將提到一些注意事項。基於我們對後期研發管線的信心，我們正在進行增量投資。

Our R&D investment reflects our commitment to innovation, accelerating our pipeline, focusing on advancing multiple potentially first-in-class and best-in-class medicines, including supporting MariTide, 2 PDUFA dates scheduled for June and 5 Phase III data readouts throughout the year. Total non-GAAP operating expenses over the second and third quarters are expected to grow at a rate comparable to the first quarter. The fourth quarter rate will normalize with a comparable expense base in the fourth quarter of 2023 since the Horizon transaction completed in early October 2023.

我們的研發投資體現了我們對創新、加速研發管線的承諾，專注於推進多種潛在的一流和一流藥物，包括支持MariTide、計劃於6 月舉行的2 個PDUFA 日期以及全年5 個III 期數據讀出。第二季和第三季的非公認會計原則營運支出總額預計將以與第一季相當的速度成長。自 Horizo​​​​n 交易於 2023 年 10 月初完成以來，第四季度費率將在 2023 年第四季與可比較費用基礎正常化。

We continue to anticipate our operating margin will improve over the next 3 quarters. We expect OI&E to be roughly $2.6 billion, which includes the interest expense related to the $28 billion of debt raised for the Horizon acquisition. We expect the non-GAAP tax rate to be in the range of 15% to 16%, primarily being driven by a more favorable jurisdictional mix of income, which includes the full year benefits associated with the inclusion of the Horizon business. Our capital expenditures guidance remains unchanged at approximately $1.1 billion in 2024. We've initiated activities to further expand manufacturing capacity for MariTide.

我們繼續預計未來三個季度的營業利潤率將有所改善。我們預計 OI&E 約為 26 億美元，其中包括與收購 Horizo​​​​n 籌集的 280 億美元債務相關的利息支出。我們預計非公認會計準則稅率將在 15% 至 16% 之間，這主要是受到更有利的司法管轄區收入組合的推動，其中包括與納入 Horizo​​n 業務相關的全年收益。我們的 2024 年資本支出指引維持在約 11 億美元不變。

We project full year Neulasta sales of approximately $500 million. Our long-term outlook remains robust. I am grateful to our 27,000-plus colleagues worldwide for their dedication to serving patients. So this concludes the financial update. I'll hand it now back to Bob for our Q&A session.

我們預計 Neulasta 全年銷售額約為 5 億美元。我們的長期前景依然強勁。我感謝全球 27,000 多名同事為病患服務的奉獻精神。財務更新到此結束。我現在將其交還給鮑勃以進行問答環節。

Okay. Thank you, Peter. And before you open the line, Julianne, let me just point out that, obviously, we have a lot of exciting opportunities here. And we're excited about the ways we think we can make a difference for patients. In terms of the opportunity in obesity, again, we recognize that there's significant interest. And we provided today's update to keep you apprised of our plans in this area. But I would just reiterate, we're focused on successfully completing and maintaining the integrity of the ongoing Phase II studies.

好的。謝謝你，彼得。朱麗安，在您接通電話之前，請允許我指出，顯然，我們這裡有很多令人興奮的機會。我們對能夠為患者帶來改變的方式感到興奮。就肥胖的機會而言，我們再次認識到人們對此很感興趣。我們提供今天的更新是為了讓您了解我們在這一領域的計劃。但我想重申一下，我們的重點是成功完成並保持正在進行的第二階段研究的完整性。

So as we turn to Q&A, just bear in mind that we're going to have to be very limited in what we can say beyond what we've already delivered in our prepared remarks on obesity and MariTide. But with that in mind, Julianne, maybe you could remind our callers of the process for asking questions.

因此，當我們轉向問答時，請記住，除了我們在有關肥胖和 MariTide 的準備好的評論中已經發表的內容之外，我們所能說的內容將非常有限。但朱莉安，考慮到這一點，也許您可以提醒我們的來電者提問的流程。

(Operator Instructions) Our first question comes from Salveen Richter from Goldman Sachs.

（操作員說明）我們的第一個問題來自高盛的 Salveen Richter。

On MariTide here, just given the move forward to Phase III, can you just remind us what you were looking to learn in the Phase II trial and likely did here, but that enabled you to kind of get confident here with the program on the [forward]?

在 MariTide 上，剛進入第三階段，您能否提醒我們您希望在第二階段試驗中學到什麼，並且可能在這裡做了什麼，但這使您對 [向前]？

Sure. Salveen, thanks for the question. Why don't you jump in, Jay?

當然。薩爾文，謝謝你的提問。傑伊，你為什麼不跳進去呢？

Yes. Thanks, Salveen, for your question. Look, we're benefiting from a really well-designed and well-executed Phase II study, a study that can teach us a lot about this medicine and how it's best dosed and received. And we're seeing from these data in aggregate a broad and differentiated profile that will guide and also encourage a Phase III clinical investigation.

是的。謝謝薩爾文提出的問題。看，我們正受益於一項精心設計和執行良好的二期研究，這項研究可以教會我們很多關於這種藥物以及如何最佳劑量和接受的知識。我們從這些數據中看到了廣泛且差異化的概況，這將指導並鼓勵 III 期臨床研究。

Our next question comes from Michael Yee from Jefferies.

我們的下一個問題來自 Jefferies 的 Michael Yee。

I appreciate the update. I think we all do. Just to clarify or to ease any investor concerns, is it safe to say that your interim looked at all doses and you feel comfortable including the highest doses and safety metrics, including bone? And all of that was looked at to date?

我很欣賞這個更新。我想我們都會這樣做。只是為了澄清或緩解投資者的擔憂，是否可以肯定地說，您的中期研究了所有劑量，並且您感到滿意，包括最高劑量和安全指標（包括骨骼）？到目前為止，所有這些都經過了審查？

Thanks a lot, Michael. I'll take this one as well. Again, a very well-designed and well-executed study, a study that's replete with measurements. This is an ongoing study, so we have to be careful to avoid in introducing an inadvertent bias or unblinding. And so we just can't comment on individual characteristics, but we're very pleased with the results to date. We're moving rapidly forward with the Phase III program as well as the diabetes Phase II. I would reiterate that all the arms remain active, and we haven't had an issue with patient dropout to date.

非常感謝，麥可。我也拿這個吧。再說一次，這是一項設計良好、執行良好的研究，一項充滿測量的研究。這是一項正在進行的研究，因此我們必須小心避免引入無意的偏見或揭盲。因此，我們無法對個人特徵發表評論，但我們對迄今為止的結果感到非常滿意。我們正在快速推進第三階段計畫以及糖尿病第二階段計畫。我要重申的是，所有部門仍然活躍，迄今為止我們還沒有遇到患者退出的問題。

I think, again, Michael, as Jay said, it's a well-designed study, and you can be sure that we review the data carefully.

我再次認為，邁克爾，正如傑伊所說，這是一項精心設計的研究，您可以確信我們會仔細審查數據。

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. Jay, you mentioned on MariTide seeing a differentiated profile. Recognize you're limited in what you can say. But as we think about areas of differentiation, it's clearly efficacy, tolerability and dosing interval. So just wondering if you can comment on which of those areas you're differentiated on? And then what benchmark are you looking to? Is it semaglutide, tirzepatide, both of those?

偉大的。 Jay，您在 MariTide 上提到看到了差異化的形象。認識到你能說的話是有限的。但當我們考慮差異化領域時，很明顯是功效、耐受性和給藥間隔。所以想知道您是否可以評論一下您在哪些領域中與眾不同？那您想要什麼基準？是索馬魯肽、替西帕肽嗎？

Thanks, Terence. Again, we can appreciate the desire to get into that detail. But maybe, Murdo, do you want to speak to the competitive differentiation? And then Jay, if there's anything you feel appropriate to elaborate on, you can jump in after Murdo.

謝謝，特倫斯。再次，我們可以理解了解這一細節的願望。但默多，也許你想談競爭差異化嗎？然後傑伊，如果您認為有什麼需要詳細說明的地方，您可以在默多之後插話。

Yes. Thanks for the question, Terence. Thanks, Bob. Obviously, we're watching the in-market products very closely with respect to differentiation. And we're also looking at products that are in the clinic being developed. And we continue to feel very confident in our ability to have a differentiated and broad profile for MariTide as we develop it in this Phase II and as we consider our broader Phase III development program.

是的。謝謝你的提問，特倫斯。謝謝，鮑伯。顯然，我們正在非常密切地關注市場產品的差異化。我們也在研究正在開發的臨床產品。當我們在第二階段開發 MariTide 並考慮更廣泛的第三階段開發計劃時，我們仍然對我們擁有差異化和廣泛的 MariTide 形象的能力充滿信心。

Yes. I'd just add, this is, Terence, a very exciting, very dynamic area. We follow the development of obesity medicines very closely. And I think in this case, the actions we're taking speak for themselves. We're hard at work planning a comprehensive and competitive Phase III program.

是的。我想補充一點，特倫斯，這是一個非常令人興奮、非常有活力的領域。我們非常密切地關注肥胖藥物的開發。我認為在這種情況下，我們正在採取的行動不言而喻。我們正在努力規劃一個全面且具競爭力的第三階段計畫。

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 and thanks for providing the update. Maybe just to shift gears a little bit to tarlatamab. With the potential launch rapidly approaching, can you just talk about the work you're doing to prepare for that launch and the strategy behind the initial launch in the late line and then the clinical and commercial work to go behind expanding the profile and potential for tarlatamab?

恭喜所有進展並感謝您提供更新。也許只是為了稍微轉向 tarlatamab。隨著潛在發布的迅速臨近，您能否談談您為該發布所做的準備工作以及後期首次發布背後的策略，以及擴大其形象和潛力背後的臨床和商業工作塔拉塔馬布？

Yes, let's take that in 2 pieces. And maybe, Murdo, you can talk about the launch. And then I'm sure, Jay, you'd like to elaborate on the thinking for the clinical development of this.

是的，我們把它分成兩個部分。默多，也許你可以談談這次發射。然後我確信，傑伊，您想詳細說明其臨床開發的想法。

Sure. Jay, thank you for the question on another exciting product in our portfolio, one that I think will deliver a lot of benefit for patients with small cell lung cancer, which is a very, very difficult diagnosis with very little in the way of highly effective treatments that deliver any kind of durable response in small cell. So we're anxiously awaiting approval from the FDA, but we are well prepared and have been for some time across our field organizations. All our field personnel, including their medical teams, are trained and prepared.

當然。 Jay，感謝您提出有關我們產品組合中另一項令人興奮的產品的問題，我認為該產品將為小細胞肺癌患者帶來很多好處，這是一種非常非常困難的診斷，幾乎沒有什麼高效的方法在小細胞中提供任何類型的持久反應的治療方法。因此，我們正在焦急地等待 FDA 的批准，但我們已經做好了充分準備，並且我們的現場組織已經做好了一段時間的準備。我們所有的現場人員，包括他們的醫療團隊，都經過訓練和準備。

We have very clear plans to reach treating physicians in very short order post approval. We have a very clear understanding of making sure that we can provide broad access to tarlatamab when it's approved. And we feel really good about this. This is a very important moment not just for Amgen but for the treatment of patients with small cell lung cancer where, quite frankly, the survival in the late-stage setting is really dismal and is a matter of single-digit months. And so we have a huge opportunity here to impact, and we're not wasting any minute, any hour or any day in our planning to do that.

我們有非常明確的計劃，將在批准後在很短的時間內到達治療醫生手中。我們非常清楚，要確保 tarlatamab 獲得批准後我們能夠提供廣泛的使用機會。我們對此感覺非常好。這不僅對安進來說是一個非常重要的時刻，對於小細胞肺癌患者的治療也是如此，坦白說，小細胞肺癌患者的晚期存活率非常低，只有個位數的幾個月。因此，我們在這裡有一個巨大的機會來發揮影響力，我們不會在計劃中浪費任何一分鐘、任何一小時或任何一天。

And Jay, thanks for highlighting the potential of this medicine, which we consider a major advance. The treatment of this disease has really not meaningfully evolved since I trained as an oncologist in the mid-90s with upfront chemotherapy and meaningful but incremental benefit to immuno-oncology therapy with PD-L1 agents today. And so this is the case where time just can't move fast enough to get this medicine into earlier lines of therapy. And so we have initiated 3 Phase III studies.

Jay，感謝您強調這種藥物的潛力，我們認為這是一個重大進步。自從我在90 年代中期接受腫瘤學家培訓以來，這種疾病的治療實際上並沒有取得有意義的進展，我接受了前期化療，並且今天使用PD-L1 藥物進行免疫腫瘤治療具有有意義但增量的益處。因此，在這種情況下，時間進展得不夠快，無法讓這種藥物進入早期治療階段。因此我們啟動了 3 項 III 期研究。

And as you asked, I'll just give an architecture of them briefly. We have a study that will compare to tarlatamab to standard of care chemotherapy. And this is in the second line dedicated patients with a primary endpoint of overall survival, and this study is enrolling. We really want to get this medicine tested in frontline therapy, where, as you must know, patients progress so quickly that a great many of them never reach the chance to receive second and third-line therapy. And so in a pair of trials, one for extensive-stage small cell lung cancer and one for limited-stage small cell lung cancer, we'll study the contribution of tarlatamab immediately following upfront therapy with response.

正如您所問的，我將簡要介紹它們的架構。我們有一項研究將 tarlatamab 與標準護理化療進行比較。這是二線專門患者的主要終點是總存活期，這項研究正在招募中。我們確實希望在一線治療中測試這種藥物，正如您必須知道的那樣，患者進展如此之快，以至於他們中的許多人從未有機會接受二線和三線治療。因此，在兩項試驗中，一項針對廣泛期小細胞肺癌，一項針對局限性小細胞肺癌，我們將在前期治療後立即研究 tarlatamab 的作用並產生反應。

We've learned through the development of these BiTE molecules that they work best when they're given as early as possible in the course of treatment for a disease. That has been the case with ALL as we move into frontline. And we've also learned that they work best when there is a low burden of disease. And so the design of these 3 Phase III studies will bring this medicine to earlier patient therapy lines. And I'll say there's been intense interest and great hope in this community. And so we expect to enroll these studies expeditiously.

透過這些 BiTE 分子的開發，我們了解到，在疾病治療過程中儘早給予它們時效果最佳。當我們進入前線時，ALL 的情況就是如此。我們也了解到，當疾病負擔較低時，它們的效果最好。因此，這 3 項 III 期研究的設計將使該藥物進入早期患者治療系列。我想說的是，這個社區有著濃厚的興趣和巨大的希望。因此，我們希望盡快註冊這些研究。

Our next question comes from Mohit Bansal from Wells Fargo.

我們的下一個問題來自富國銀行的 Mohit Bansal。

I have a question regarding the manufacturing of AMG 133. Could you help us understand how complicated or simpler it is versus the traditional GLP-1s peptide base in terms of complexity as well as cost? And what kind of investment do you think we should be expecting as you go -- as you embark on this journey?

我有一個關於 AMG 133 製造的問題。您認為當您踏上這段旅程時，我們應該期待什麼樣的投資？

Mohit, I don't think we're intimidated about the challenge on the manufacturing or the process development front. I think, again, we've established ourselves firmly as a world leader in biotherapeutic manufacturing. And as you know, this is a therapy that's based on a antibody backbone. So it's right down the middle of the fairway for us. We've -- not lost on us that these competitors who are in the market now have found it difficult to maintain supply of these medicines, and I'm sure that's not lost in the patients either.

Mohit，我認為我們不會被製造或工藝開發方面的挑戰嚇倒。我認為，我們再次牢牢確立了自己在生物治療製造領域的世界領導者地位。如您所知，這是一種基於抗體骨架的療法。所以對我們來說它就在球道中間。我們並沒有忘記，市場上的這些競爭對手現在發現很難維持這些藥物的供應，我相信病人也沒有忘記這一點。

And we're determined to do our best to make sure that we uphold our long tradition of supplying every patient, every time in the marketplace. So again, we think this is down the middle of the fairway in terms of the technical challenges that we need to address. We think that -- we look forward to being able to do that. And again, as I said, maintaining our track record of every patient, every time.

我們決心盡最大努力，確保秉承我們每次在市場上為每位患者提供服務的悠久傳統。所以，我們再次認為，就我們需要解決的技術挑戰而言，這還處於正軌。我們認為——我們期待能夠做到這一點。正如我所說，每次都保留每位患者的追蹤記錄。

In terms of your question about what it will require from us over time, obviously, to the extent that, that becomes meaningful, Mohit, we'll have the opportunity to address it down the road. But as Peter said in his remarks, our capital expenditure guidance for the year embraces the activity that we have underway to make ourselves ready for the clinical and commercial challenge that we see imminently.

至於你關於隨著時間的推移我們需要做什麼的問題，顯然，在這變得有意義的情況下，莫希特，我們將有機會在未來解決這個問題。但正如彼得在演講中所說，我們今年的資本支出指導涵蓋了我們正在進行的活動，以便為我們即將面臨的臨床和商業挑戰做好準備。

Our next question comes from Umer Raffat from Evercore ISI.

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

I'll spare all my curiosities on your ongoing trial. But I will ask this. One, on manufacturing capacity. I'm curious, is your aim to have 1 million to 2 million patients worth of capacity or 5 million to 10 million? You can imagine from a modeling perspective, from a CapEx side, this would be relevant, knowing obviously how much manufacturing experience and capacity you guys have. And then secondly, the -- is it a pen device? I know you mentioned it's a "handheld patient-friendly auto-injector" which is a single injection. But is it a pen device or is it something else?

我會放棄對你正在進行的審判的所有好奇。但我會問這個。一、關於製造能力。我很好奇，你們的目標是擁有 100 萬到 200 萬患者的容量，還是 500 萬到 1000 萬的容量？你可以從建模的角度想像，從資本支出的角度來看，這將是相關的，清楚地知道你們擁有多少製造經驗和能力。其次，它是筆設備嗎？我知道您提到這是一種“手持式患者友好型自動注射器”，它是單次注射。但它是筆設備還是其他東西？

Yes. So Umer, I don't think we're going to say anything more about the delivery -- expected delivery device at this point. I think we were as clear as we could be. And we think it will be patient-friendly and convenient. And with respect to the quantity of patients that we expect to serve, we recognize that the unmet need here is very large, and we want to be in position to supply the patients that we think will be interested in the differentiated profile of our medicine.

是的。所以，烏默，我認為我們不會再談論有關交付的任何內容——此時預期的交付設備。我認為我們已經盡可能清楚了。我們認為這將對患者友好且方便。就我們期望服務的患者數量而言，我們認識到這裡未滿足的需求非常大，我們希望能夠為我們認為會對我們的差異化藥物感興趣的患者提供服務。

I would point out to you and I hope you're aware that we are already serving millions of patients today around the globe with our biotherapeutics. So again, we're used to supplying many millions of patients with antibody-based therapies. I think we're pushing up on 8 million Prolia patients right now worldwide. So we understand what it takes to supply large quantities of antibody therapies and what it means to do that with successful delivery devices.

我想向您指出，我希望您知道，我們今天已經在用我們的生物治療藥物為全球數百萬患者提供服務。同樣，我們習慣為數百萬患者提供基於抗體的療法。我認為我們現在正在全球推廣 800 萬 Prolia 患者。因此，我們了解供應大量抗體療法需要什麼，以及使用成功的輸送設備來實現這一目標意味著什麼。

And I'm sure it's not lost on all of you that the fact that, as Jay said, the delivery dosing schedule is likely to be monthly or less frequently implies far fewer injection devices than competitors who, for example, are administering a weekly therapy. So again, all in all, we recognize the reasons for your questions on supply. But I hope you recognize as well the reasons why we're confident that we'll be up to that challenge.

我相信大家都沒有忘記，正如傑伊所說，交付劑量計劃可能是每月一次或頻率較低，這意味著注射設備比競爭對手要少得多，例如每週進行一次治療的競爭對手。總而言之，我們再次重申您提出供應問題的原因。但我希望您也能認識到我們有信心應對這項挑戰的原因。

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 updates as well. And just a question on your larger obesity and cardiometabolic strategy. Certainly, with the news on 786 and as you speak to MariTide's efforts on convenience, how are you thinking about oral options within your portfolio now that you are certainly levered towards MariTide as the lead asset? I'm just curious how oral options should fit in with the portfolio longer term.

也恭喜您的更新。只是關於您的肥胖和心臟代謝策略的問題。當然，隨著 786 的消息以及您談到 MariTide 在便利性方面所做的努力，既然您肯定將 MariTide 作為主要資產，那麼您如何考慮您的投資組合中的口頭選擇權？我只是好奇口頭選擇權如何與長期投資組合相適應。

Gregory, thank you. This differentiated profile that we're seeing with MariTide really raises the bar for Amgen obesity medicines. And the profile for 786 just did not meet that bar in our assessment. We do have a pipeline, a strong pipeline of earlier assets. There are incretin as well as non-incretin based. Some are injectable and some are oral. And we believe that the heterogeneity, the diversity of the marketplace of -- and honestly, the different types of patients that will need medicines for obesity and all the obesity-related conditions demands medicines with different profiles, and we are hard at work on that.

格雷戈里，謝謝你。我們在 MariTide 上看到的這種差異化特徵確實提高了安進肥胖藥物的標準。 786 的配置並未達到我們評估中的標準。我們確實有一個管道，一個強大的早期資產管道。有腸促胰島素和非腸促胰島素。有些是注射劑，有些是口服劑。我們相信，市場的異質性和多樣性——老實說，需要治療肥胖藥物的不同類型的患者以及所有與肥胖相關的疾病需要具有不同特徵的藥物，我們正在努力解決這個問題。

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 MariTide, I'll ask a question on differentiation that I think you should be able to answer, which is, can you remind us what in the past you felt would be differentiating based on what the Phase I showed? So I'm not asking you to comment on what you just recently saw, but just a reminder of past comments on what you felt the data seemed to show in that front. Less frequent dosing frequency, of course, is the obvious one, but what else?

在 MariTide 上，我會問一個關於差異化的問題，我認為你應該能夠回答，也就是說，你能否提醒我們，根據第一階段所展示的內容，你過去認為什麼會是差異化的？因此，我並不是要求您對您最近看到的內容發表評論，而只是提醒您過去對您認為數據似乎在前面顯示的內容的評論。當然，較不頻繁的給藥頻率是顯而易見的，但還有什麼呢？

Yes. Tim, I think we've been fairly consistent on what we believe an opportunity is to differentiate in the market, both in the past and obviously as we see the interim analysis of these results. We think that we have a broad opportunity to differentiate with MariTide. And by that, I mean a broad differentiated profile on a number of fronts. And we continue to believe that we will be able to move into the market with a differentiated product, establish MariTide as a really good opportunity to address unmet medical needs and provide access for millions of patients as we go forward.

是的。提姆，我認為我們對於在市場中實現差異化的機會一直相當一致，無論是在過去還是在我們看到這些結果的中期分析時都是如此。我們認為我們有廣闊的機會與 MariTide 實現差異化。我的意思是在許多方面都有廣泛的差異化形象。我們仍然相信，我們將能夠以差異化產品進入市場，將 MariTide 打造成一個真正的好機會來解決未滿足的醫療需求，並在我們前進的過程中為數百萬患者提供機會。

Our next question comes from Yaron Werber from TD Cowen.

我們的下一個問題來自 TD Cowen 的 Yaron Werber。

Congrats on the update. So I'm just going to ask a question I think you can answer on -- it's a little technical in nature. In the interim analysis for MariTide, was it blinded or not blinded? And then just remind us, is there a dose titration in that study?

恭喜更新。所以我只想問一個我認為你可以回答的問題——本質上有點技術性。在 MariTide 的中期分析中，它是盲目的還是不盲目的？然後提醒我們，該研究中有劑量滴定嗎？

Sure. This is Jay, Yaron. Thank you. The interim analysis, we as R&D leaders have had an ability to see the assigned treatment arms of the study. But importantly, this interim analysis is blinded to investigators and to participants to preserve the integrity of the study.

當然。這是傑伊，亞倫。謝謝。根據中期分析，我們作為研發領導者有能力查看研究指定的治療組。但重要的是，這種中期分析對研究人員和參與者來說是不知情的，以保持研究的完整性。

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。

Thanks for the question. Yet another one on MariTide. Just given Amgen's cardio portfolio and focus, do you have any updated thoughts on expanding the program beyond just diabetes and obesity? Obviously, recognizing that you now have a better picture of the safety and tolerability profile.

謝謝你的提問。 MariTide 上的另一個。考慮到安進的有氧運動產品組合和重點，您對於將該計劃擴展到糖尿病和肥胖症之外有什麼最新的想法嗎？顯然，認識到您現在對安全性和耐受性有了更好的了解。

Yes. Thank you, Geoff, for asking and allowing a clarification. What we're observing with MariTide and what we intended for the development of MariTide continues at pace. And we're preparing for a broad Phase III program that can work to address the unmet needs in obesity and a number of obesity-related conditions and, as you heard, in diabetes as well.

是的。謝謝傑夫提出問題並允許澄清。我們在 MariTide 中觀察到的情況以及我們對 MariTide 開發的預期仍在繼續。我們正在準備一項廣泛的第三階段計劃，該計劃可以致力於解決肥胖和許多與肥胖相關的疾病以及正如您所聽到的糖尿病方面未得到滿足的需求。

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

我們的下一個問題來自 BMO 資本市場的 Evan Seigerman。

I'm not going to ask on MariTide, although I am tempted to. I actually want to ask one on rocatinlimab. So with the Horizon ROCKET studies upcoming, can you just talk us through what the differentiations you want to see? And how would you position this asset versus, say, the entrenched Dupixent and RINVOQ in the atopic dermatitis space?

我不會在 MariTide 上詢問，儘管我很想這麼做。我其實想問一個關於 rocatinlimab 的問題。那麼，隨著地平線火箭研究即將到來，您能告訴我們您希望看到哪些差異化嗎？與異位性皮膚炎領域根深蒂固的 Dupixent 和 RINVOQ 相比，您如何定位這項資產？

Two pieces. Maybe Jay can address the clinical perspective on differentiation. And then Murdo, to the extent it's appropriate, you can jump in on how to think about positioning it.

兩塊。也許傑伊可以從臨床角度闡述分化問題。然後默多，在適當的範圍內，你可以加入進來思考如何定位它。

Yes. It sounds as though, Evan, you're close to this work. But as you know, rocatinlimab is an OX40-directed monoclonal antibody, afucosylated IgG1, a strong ADCC. We have a program called ROCKET that has over 2,800 patients enrolled. And so to address differentiation, I'm going to limit that maybe scope to the atopic dermatitis space. And here in the Horizon, the so called Horizon study, it's a Phase III randomized controlled trial. It's in moderate to severe atopic dermatitis. It's 726 patients actually enrolled. And in this case, it's rocatinlimab every 4 weeks against placebo with a 24-week treatment readout. We have endpoints at 16 and 24 weeks. We will -- it's always apples to oranges to compare between trials, but we hope to observe and expect to observe in moderate to severe atopic dermatitis a very competitive profile with strong efficacy and excellent patient experience and tolerability. Here, we think about Dupixent and follow that work in its development closely. And Murdo, I leave it to you to talk through how to best think about differentiation.

是的。埃文，聽起來你已經很接近這項工作了。但如您所知，rocatinlimab 是一種 OX40 定向單株抗體，無岩藻糖基化 IgG1，是一種強 ADCC。我們有一個名為 ROCKET 的項目，已有 2,800 多名患者參加。因此，為了解決差異化問題，我將把範圍限制在異位性皮膚炎領域。在 Horizo​​n 中，即所謂的 Horizo​​​​n 研究，這是一項 III 期隨機對照試驗。這是中度至重度異位性皮膚炎。實際登記了 726 名患者。在這種情況下，每 4 週使用一次 rocatinlimab，對比安慰劑，並進行 24 週的治療讀數。我們的終點為 16 週和 24 週。我們將——在試驗之間進行比較總是從蘋果到橙子，但我們希望觀察並期望在中度至重度異位性皮膚炎中觀察到非常有競爭力的特徵，具有強大的功效和出色的患者體驗和耐受性。在這裡，我們考慮 Dupixent 並密切關注其開發工作。默多，我讓你來談談如何最好地思考差異化。

Yes. Thanks, Jay. And thanks for the question, Evan. We are studying, as Jay mentioned, a broad population of patients in atopic dermatitis. So we will have some patients that will have previous biologic experience as well as bio-naive. So we will know how to position this product effectively in the market. I would just -- I would perhaps use the recent experience of how we launched TEZSPIRE and differentiated against Dupixent in a different indication using a highly differentiated mechanism and the fact that prescribers in this area are looking for alternatives to nonresponsive patients and to bio-naive patients. So we feel good about the opportunity here. But obviously, we have to await data and see the readouts of the clinical trials.

是的。謝謝，傑伊。謝謝你的提問，埃文。正如傑伊所提到的，我們正在研究大量異位性皮膚炎患者。因此，我們將有一些患者既有生物學經驗，也沒有生物學經驗。這樣我們就會知道如何在市場上有效地定位該產品。我可能會利用最近的經驗，即我們如何推出TEZSPIRE，並使用高度差異化的機制在不同的適應症中與Dupixent 進行區分，以及該領域的處方者正在尋找無反應患者和生物治療的替代品這一事實患者。所以我們對這裡的機會感到很高興。但顯然，我們必須等待數據並查看臨床試驗的結果。

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。

Can you just elaborate a little bit more on TEZSPIRE and its potential role in COPD post the Phase II data? And maybe as part of that, how broadly do you expect to study this compound in Phase III, I guess, given the efficacy across the different eosinophil counts that we saw in the Phase II program?

您能否詳細說明一下 TEZSPIRE 及其在 II 期資料後在 COPD 中的潛在作用？也許作為其中的一部分，考慮到我們在第二階段項目中看到的不同嗜酸性粒細胞計數的功效，我想您預計在第三階段研究這種化合物的範圍有多大？

Yes. Thanks for the question, Chris. It's Jay again. And so the Phase II COPD data will be presented in an oral presentation, as I mentioned, at the American Thoracic Society Meeting later this month. And so as that work and its abstract are presently embargoed, there is a natural limit to what I'm able to share. But what I will remind, as you asked more mechanistically, is that TSLP comes from this family of what are called alarmins. And they do just what it sounds like they do.

是的。謝謝你的提問，克里斯。又是傑伊。因此，正如我所提到的，第二階段慢性阻塞性肺病數據將在本月稍後的美國胸腔科學會會議上以口頭報告的形式公佈。由於該作品及其摘要目前被禁止，我能夠分享的內容自然受到限制。但我要提醒的是，正如您更機械地詢問的那樣，TSLP 來自所謂的警報素家族。他們所做的就是聽起來的那樣。

An epithelium, inflamed or irritated or activated, that's inflamed releases TSLP and triggers what's called type 2 inflammation. There are a number of signaling factors that participate in type 2 inflammation. But then, TSLP then converges down in this type 2 T-cell inflammatory milieu in response also involving eosinophils. And that's why we often invoke that measurement in clinical investigation.

發炎、刺激或活化的上皮會釋放 TSLP 並引發所謂的 2 型發炎。有許多訊號因子參與第 2 型發炎。但隨後，TSLP 在這種 2 型 T 細胞發炎環境中收斂，作為反應，也涉及嗜酸性粒細胞。這就是為什麼我們經常在臨床研究中引用這種測量方法。

The rationale for COPD is as strong as it is for asthma. But COPD, if you must know, is a much more heterogeneous disease than asthma. And so the design of this clinical trial appreciated and understood that and built into it some predefined stratifications for analysis, one of which was this eosinophil threshold of 150 cells per microliter.

治療慢性阻塞性肺病的理由與治療氣喘的理由一樣充分。但如果您必須知道的話，慢性阻塞性肺病是一種比氣喘更具異質性的疾病。因此，這項臨床試驗的設計認識並了解這一點，並在其中內建了一些預定義的分析分層，其中之一就是每微升 150 個細胞的嗜酸性粒細胞閾值。

And so we look forward to sharing the full data. We have already disclosed that there's clinically meaningful activity of the molecule in this randomized controlled trial. And so please expect more at the ATS. You asked about the more broad development. You are right that TSLP is not only a feature of an inflamed airway epithelium but other epithelial surfaces as well. Hence, our interest to develop it in eosinophilic esophagitis as well as chronic rhinosinusitis with nasal polyps. And both of these diseases are characterized molecularly by type 2 inflammation.

因此，我們期待分享完整的數據。我們已經透露，在這項隨機對照試驗中，該分子具有臨床意義的活性。所以請對 ATS 抱持更多期待。你問的是更廣泛的發展。你是對的，TSLP 不僅是發炎的氣道上皮的特徵，也是其他上皮表面的特徵。因此，我們有興趣將其開發用於嗜酸性粒細胞性食道炎以及伴有鼻息肉的慢性鼻竇炎。這兩種疾病的分子特徵都是第 2 型發炎。

Our next question comes from James Shin from Deutsche Bank.

我們的下一個問題來自德意志銀行的 James Shin。

This one is a little bit off the reservation. It's for Jay and on oncology. It's for AMG 651, the EGFR CD3. Just wanted to get your thoughts on that. I think there's going to be some data coming up soon, and there's some other data that's come out recently from peers.

這家有點超出預訂範圍了。這是給傑伊和腫瘤學的。適用於 AMG 651，即 EGFR CD3。只是想聽聽您對此的想法。我認為很快就會出現一些數據，最近同行還會發布一些其他數據。

Yes. Well, I would say this, James. Thanks for the question. We have a large experience of developing CD3 bispecifics. And we have learned over time to tune the potency of engagement to the cell surface antigen to the degree of engagement and activation of the CD3. And there is no news to share with you at this moment. We continue to study this and other solid tumor-targeting T-cell-engaging bispecifics, really buoyed by the confidence and the guidance from tarlatamab and xaluritamig. So I would expect more in the future on that medicine as well as other solid tumor-targeting bispecific T-cell engagers.

是的。好吧，我會這麼說，詹姆斯。謝謝你的提問。我們在開發 CD3 雙特異性抗體方面擁有豐富的經驗。隨著時間的推移，我們已經學會了將與細胞表面抗原的結合效力調整到 CD3 的結合和活化程度。目前沒有消息可以與您分享。我們繼續研究這種和其他實體瘤靶向 T 細胞參與雙特異性藥物，真正受到 tarlatamab 和 xaluritamig 的信心和指導的鼓舞。因此，我對這種藥物以及其他針對實體瘤的雙特異性 T 細胞接合劑未來會有更多期待。

Our next question comes from Kripa Devarakonda from Truist Securities.

我們的下一個問題來自 Truist Securities 的 Kripa Devarakonda。

I have a question on TEPEZZA in TED. Can you please talk about where you are with this subcu program? I think the Phase III is ongoing. Just a little bit of update on that. And as you continue to treat more patients with TED, what are you hearing about concerns around safety concerns? And is that having any impact on uptake?

我在 TED 上有一個關於 TEPEZZA 的問題。您能談談您對這個 subcu 程式的進展嗎？我認為第三階段正在進行中。只是對此進行一點更新。隨著您繼續用 TED 治療更多患者，您聽到了哪些關於安全問題的擔憂？這對吸收有影響嗎？

We'll take it in 2 parts. Jay, you can address the clinical questions. And then to the extent that, Vikram, you want to share any thoughts on the marketplace, jump in.

我們將把它分成兩部分。傑伊，你可以解決臨床問題。然後，維克拉姆，如果您想分享對市場的任何想法，請加入。

Yes, thanks for the question. The development of a subcutaneous administration of TEPEZZA is a major priority for Amgen R&D in the program. We have initiated a Phase III study. This will be -- this is in moderate to severe active TED. And the design is akin to what we have reported already with the intravenous label-enabling studies completed to date. And Vikram, if you want to speak to the clinical experience.

是的，謝謝你的提問。 TEPEZZA 皮下給藥的開發是安進研發部門在該計劃中的一個主要優先事項。我們已經啟動了 III 期研究。這將是——這是在中度到重度活躍的 TED 中。該設計類似於我們已經報告的迄今為止已完成的靜脈注射標籤支持研究。如果你想談談臨床經驗，維克拉姆（Vikram）。

Yes, I think -- so thanks for the question. I think the question was around AEs and if that is limiting growth. And I imagine, Kripa, that you're maybe specifically referring to hearing loss or about hearing loss.

是的，我想——謝謝你的提問。我認為問題在於不良事件以及這是否限制了成長。我想，Kripa，您可能專門指的是聽力損失或聽力損失。

So let's start at the top. TEPEZZA, it very effectively treats TED, which we all now is a pretty severe and debilitating disease. IGF-1, we know is going to be involved in hearing function. So during the clinical assessment and the clinical development of TEPEZZA, we very carefully have -- we looked at -- we assessed hearing function. We now have included this in the warnings and precautions section of the PI, along with a recommendation for assessment and monitoring. It's important because patients who use TEPEZZA should be monitored for any specific experience with hearing impairment.

那麼讓我們從頂部開始。 TEPEZZA，它可以非常有效地治療 TED，這是一種非常嚴重且使人衰弱的疾病。我們知道 IGF-1 與聽力功能有關。因此，在 TEPEZZA 的臨床評估和臨床開發過程中，我們非常仔細地——我們觀察——我們評估了聽力功能。我們現在已將其納入 PI 的警告和預防措施部分，以及評估和監控建議。這很重要，因為應監測使用 TEPEZZA 的患者是否有任何特定的聽力障礙經驗。

We're also working with professional societies to increase education. And while many physicians do use a baseline hearing assessment, getting it in the label helps standardize this approach, okay? So after working through the management of this with HCPs, this has not generally turned to be a barrier for growth as physicians generally understand the favorable risk-benefit profile of TEPEZZA.

我們也與專業協會合作以加強教育。雖然許多醫生確實使用基線聽力評估，但將其納入標籤有助於標準化這種方法，好嗎？因此，在與 HCP 進行管理後，這通常不會成為成長的障礙，因為醫生普遍了解 TEPEZZA 有利的風險效益狀況。

Thank you. So Julianne, we're pushing up to the appointed bottom of the hour here, but we still have a few questions in the queue. So we'll take a couple more to try to get through your questions. If we don't get to everybody, obviously, Justin and his team will be around this evening to answer any questions. But let's try and click through these, the ones we can quickly, Julianne.

謝謝。朱莉安，我們已經到了指定的下班時間，但我們還有一些問題需要解答。因此，我們將採取更多措施來嘗試解決您的問題。如果我們不能聯繫到所有人，賈斯汀和他的團隊顯然會在今晚回答任何問題。但是，讓我們嘗試點擊這些，我們可以快速點擊這些，朱麗安。

Our next question comes from Michael Schmidt from Guggenheim Partners.

我們的下一個問題來自古根漢合夥人公司的麥可‧施密特。

I had one on BLINCYTO, which has recently gained some commercial momentum recently. And there was some interesting academic data reported last week in Nature Medicine showing some activity in RA. And so I was just wondering if you have any plans? Or how are you thinking about potentially developing BLINCYTO or maybe other BiTEs in autoimmune?

我在 BLINCYTO 上有一個，它最近獲得了一些商業動力。上週《自然醫學》雜誌報導了一些有趣的學術數據，顯示了 RA 的一些活動。所以我想知道你有什麼計劃嗎？或者您如何考慮開發 BLINCYTO 或其他用於自體免疫的 BiTE？

Sorry. In autoimmune disorders?

對不起。自體免疫疾病？

Yes.

是的。

Thanks for your question. With very deep expertise here in CD19-directed therapeutics, with deep and committed expertise in inflammation and autoimmunity, we've been following this space very closely, the early suggestive evidence from CAR T-cell therapy and, more recently, this work that's been reported in systemic sclerosis. And as you noted, 6 patients with quite refractory rheumatoid arthritis is very exciting to see. And so you can imagine that we're well organized around this opportunity. And we found that work quite inspiring and we'll have more to report in the future.

謝謝你的提問。憑藉著在CD19 導向療法方面非常深厚的專業知識，以及在發炎和自體免疫方面深厚而專注的專業知識，我們一直在非常密切地關注這個領域，來自CAR T 細胞療法的早期提示性證據，以及最近的這項工作在系統性硬化症中已有報告。正如您所指出的，6 名患有難治性類風濕性關節炎的患者令人非常興奮。所以你可以想像我們圍繞這個機會組織得很好。我們發現這項工作非常鼓舞人心，我們將來會有更多報告。

Julianne, I think we've got time for one more question.

朱莉安，我想我們還有時間再問一個問題。

Our last question will come from Gary Nachman from Raymond James.

我們的最後一個問題將來自雷蒙德詹姆斯的加里納赫曼。

Great. So back to MariTide, I have to finish with that. As you're planning for the Phase III studies, do you have a sense of when you could start those? How big those might be? And anything about design and overall timing relative to other Phase III studies in this space? And any strategies you have to accelerate those studies as quickly as possible and how you'll incorporate both U.S. and ex U.S. in the program?

偉大的。回到 MariTide，我必須結束這個話題。當您計劃進行 III 期研究時，您知道什麼時候可以開始這些研究嗎？那些可能有多大？與該領域其他 III 期研究相比，設計和整體時間安排有何變化？您有什麼策略可以盡快加速這些研究，以及如何將美國和前美國納入該計劃？

So Gary, again, we appreciate it. I can understand why you'd be asking those questions. As I said in my remarks, we will do our level best now to successfully complete the Phase II study and then work swiftly with regulators to agree the program that establishes safety and efficacy in Phase III, and we'll do that as swiftly as we can. We recognize there's a huge unmet need still in the marketplace, and we believe we have an asset that can help address that. But Jay, I don't know whether you feel you can say anything more specific, but jump in if you do.

所以加里，我們再次表示感謝。我能理解你為什麼會問這些問題。正如我在演講中所說，我們現在將盡最大努力成功完成第二階段研究，然後迅速與監管機構合作，就確定第三階段安全性和有效性的計劃達成一致，我們將盡快做到這一點能。我們認識到市場上仍然存在巨大的未滿足需求，我們相信我們擁有可以幫助解決這個問題的資產。但傑伊，我不知道你是否覺得你可以說得更具體一些，但如果你願意的話，請加入。

Yes, I'd say the same, Bob. Gary, as you know, this is one part, collecting the data that regulators rightly expect, and ongoing conversations around the design. This study is moving as rapidly as possible within -- this program is moving as rapidly as possible within the organization, you can rest assured.

是的，我也會這麼說，鮑伯。加里，如您所知，這是一部分，收集監管機構正確期望的數據，以及圍繞設計的持續對話。這項研究正在以盡可能快的速度在組織內進行，您可以放心，該計劃正在組織內以盡可能快的速度進行。

Okay. Well, again, let me thank you all for joining the call and reiterate that Justin and his team will be around if you have any further questions. We look forward to having an opportunity to talk to you in the summer after the second quarter and provide update on the flow of information that we expect to generate between now and then on the many programs that we've referred to on the call. So thank you for your interest. Appreciate it.

好的。好吧，讓我再次感謝大家加入電話會議，並重申，如果您有任何其他問題，賈斯汀和他的團隊將隨時為您服務。我們期待在第二季度之後的夏天有機會與您交談，並提供我們預計從現在到那時我們在電話會議中提到的許多計劃產生的信息流的最新信息。感謝您的關注。欣賞它。

This concludes our 2024 Q1 earnings call. You may now disconnect.

我們的 2024 年第一季財報電話會議到此結束。您現在可以斷開連線。