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)

我叫朱莉安 (Julianne)，今天我將擔任安進 2024 年第一季財務業績電話會議的主持人。 （操作員指令）

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

現在我想介紹投資者關係副總裁賈斯汀·克萊斯 (Justin Claeys)。克萊斯先生，現在您可以開始了。

Thank you, Julianne. Good afternoon, and welcome to our 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，隨後傑伊·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回顧。

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了適當的對帳。我們也將做出一些前瞻性陳述，這些陳述受我們的安全港聲明的約束。請注意，實際結果可能會大不相同。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。謝謝你，賈斯汀，也謝謝今天的來電者加入我們。這是安進公司忙碌又令人興奮的時刻。從我們的結果可以看出，我們現有的藥物正在惠及世界各地更多的患者，我們中後期研發管線中一系列潛在的一流藥物正在不斷推進，隨著我們整合乾濕實驗室能力和利用變革性技術，我們重新定義了研究的可能性。

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，這些亮點讓我非常有信心，我們正走在實現有吸引力的長期成長的道路上。首先，我們在普通醫學、腫瘤學和發炎領域有許多產品，它們發展勢頭強勁，仍有很大的成長空間。其中包括 Repatha，上漲 33%； EVENITY，上漲35%； BLINCYTO，上漲 26%； TEZSPIRE 上漲 80%。我們預計 BLINCYTO 將於 6 月獲得批准，這將加速我們將其融入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治療慢性阻塞性肺病方面具有吸引力的潛在潛力。慢性阻塞性肺病 (COPD) 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 在這方面發揮的潛力感到非常興奮。

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，本季貢獻了近 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 等同類首創的早期生命週期藥物具有巨大的上漲潛力。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，我們上週宣布了即將向歐盟提交 TEPEZZA 審批的計劃。

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 four 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、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契合。第三，我們正在快速推進中後期研發管線中的一些有前景的新藥，涵蓋了我們的所有四個治療領域。例如，我們正在等待塔拉塔單抗的批准，並期待為小細胞肺癌患者帶來這項變革性創新。 Tarlatamab 是第一個被證明對常見實體腫瘤具有顯著臨床活性的 T 細胞介導療法，這是安進公司開創並繼續引領的領域的分水嶺時刻。

Looking to the rest of the year, we anticipate data readouts from five 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，我們預計將公佈五項 III 期試驗的數據。此外，我們今天宣布開發 KEYTRUDA 的生物相似藥，以期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，我們目前擁有並正在研發多種藥物，這些藥物將使我們能夠滿足全球數百萬患者的需求，並在未來十年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 a 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，讓我補充另一個重要更新。雖然我們通常不會對中期數據發表評論，尤其是對於第二階段試驗，但我們認識到人們對 MariTide 的肥胖症有濃厚的興趣，因此我們今天將提供額外的評論。此項研究的第二階段中期分析已經完成，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。經過中期分析，我想說我們對 MariTide 的差異化產品充滿信心，並相信它將滿足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，其中包括肥胖症、肥胖相關疾病和糖尿病。顯然，我們希望仔細完成我們正在進行的第二階段試驗，然後儘快採取適當行動，在第三階段試驗中確定這種潛在藥物的安全性和有效性。我們也已啟動活動，進一步擴大生產能力，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.

傑伊將針對這項正在進行的研究發表一些補充評論。我想請您認識到，為了在本次更新之後保護研究的完整性，我們不希望在完成之前進一步討論這些數據。像往常一樣，我要感謝我們在世界各地的員工對我們的業務和我們所服務的患者的承諾。傑伊，我將把它交給你。

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.

謝謝你，鮑勃，大家下午好。讓我從 MariTide 開始。重申鮑伯的評論，我們對迄今為止 MariTide 所取得的成果非常滿意。我們對正在進行的第二階段試驗的整體進展感到非常滿意。所有組別均保持活躍，患者退出並非問題，我們完全有望在 2024 年底獲得這項 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 的差異化特徵，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，我們計劃啟動一項額外的專門 II 期試驗，研究 MariTide 對肥胖和非肥胖患者糖尿病的治療效果。這項新試驗並不是我們針對肥胖患者進行 III 期臨床試驗的門檻。根據正在進行的 II 期肥胖症研究的劑量和時間表信息，專門的 II 期糖尿病研究符合 III 期的監管要求，是 MariTide 邁向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，我們希望透過方便、手持、患者友好的自動注射器設備來提供 MariTide，假設最終獲得批准，每月或更頻繁地進行單次注射。在整個產品組合中，我們目前優先考慮差異化藥物，即那些能為患者帶來最大利益的藥物。鑑於我們已經看到的 AMG 786 的概況，我們不會進行進一步的開發。相反，在肥胖症方面，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 five 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，在第一季度，我們還迅速推進了多樣化的臨床管線，這些管線可能是一流的或最好的專案。展望未來，2024 年的剩餘時間有望成為令人興奮的研究和開發時期，6 月將有 2 個 PDUFA 日期，分別針對小細胞肺癌中的 tarlatamab 和成人急性淋巴細胞白血病中的 BLINCYTO，以及 5 個 III 期數據讀數。每個里程碑都代表著我們朝著為真正需要的患者提供突破性治療的使命邁出了重大一步。

Moving to olpasiran, we're pleased to announce that we've completed enrollment of the OCEAN(a)-Outcomes trial, a Phase III cardiovascular outcomes 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.

談到奧帕西崙，我們很高興地宣布，我們已經完成了 OCEAN(a)-Outcomes 試驗的招募，這是一項關於奧帕西崙的 III 期心血管結果研究，奧帕西崙是我們潛在的同類最佳的 Lp(a) 靶向小幹擾 RNA 藥物。我們致力於為心血管疾病患者提供協助，也表達了醫學界的濃厚興趣，在短短 15.5 個月內，我們成功招募了全球 7,297 名患者。據我們所知，這是同等規模中招募速度最快的第三階段結果研究。需要提醒的是，Lp(a) 是一種基因定義的心血管風險因素，約 20% 的個體的該因素升高，目前尚無有效或有針對性的治療方法。

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效果的差異化療法來實現高信念目標。從 tarlatamab 開始，這是針對小細胞肺癌的 DLL3 的同類首創 BiTE 分子，我們將繼續按照 FDA 的優先審查程序，於 6 月 12 日獲得 PDUFA 批准。

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 three Phase III studies now initiated in both extensive stage and limited stage disease.

我們很高興 tarlatamab 有可能成為小細胞肺癌的首個選擇性治療方法。基於在接受二線和三線治療的患者中觀察到的單一藥物的顯著活性，我們正在迅速推進塔拉塔單抗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三項 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.

在較低腫瘤負擔的背景下，在早期階段研究塔拉塔單抗的理由源自於我們在 B 細胞 ALL 中使用 BLINCYTO 的經驗。我們觀察到微小殘留疾病陰性患者的整體存活率顯著提高。這些 BLINCYTO 數據提供的證據表明，以這種方式引導 T 細胞是尋找和消除殘留癌細胞的有效方法，而殘留癌細胞是導致疾病復發的主要因素。我們希望能夠在塔拉塔單抗的基礎上進一步拓展這項見解，其對早期小細胞肺癌患者的類似活性將非常顯著地改善面臨這種惡性癌症挑戰的患者的治療結果。

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 是一個重大進展，它是第一個在常見實體瘤中證明有效的雙特異性 T 細胞接合劑，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。我們的首創 STEAP1 CD3 雙特異性分子 xaluritamig 在實體腫瘤（即前列腺癌）中也表現出明確的活性，並且在去年秋季公佈令人鼓舞的 I 期數據後繼續取得進展。我們目前已全面招募單藥治療 I 期劑量擴展的患者，並繼續招募減少監測和門診隊列的患者。此外，新型荷爾蒙療法中與 xaluritamig 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 two 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，我們正在迅速推進 AMG 193，這是我們的口服 PRMT5 抑制劑，針對 MTAP 無效的實體腫瘤。我們已推進單藥治療劑量擴展研究，並已啟動另外兩項 I 期研究，針對胸腔、胃腸道、膽道和胰腺癌中的 MTAP 無效腫瘤，探索與標準治療的相關組合。

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，我們受到了 COURSE IIa 期概念驗證研究結果的鼓舞，該研究研究了 TEZSPIRE 對中度至極重度 COPD 患者的影響。這項研究的目的是測試 TSLP 在嗜酸性粒細胞水平的廣泛範圍內的抑制情況，而不考慮發炎驅動因素、肺氣腫、慢性支氣管炎和吸煙狀況。儘管與安慰劑相比，TEZSPIRE 在使中度或重度 COPD 急性加重年發生率方面取得了具有臨床意義的 17% 的降低，但這一結果可能由於患者總體人口統計數據廣泛而缺乏統計學意義。

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，在計劃的患者亞組中，基線血液嗜酸性粒細胞計數大於 150 個/微升，COPD 急性發作的減少幅度更大，而基線計數大於 300 個/微升的少數受試者的急性發作有進一步減少的趨勢。

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.

我們正與合作夥伴阿斯特捷利康一起積極規劃 TEZSPIRE 在 COPD 治療領域的第三階段開發。除了慢性阻塞性肺病 (COPD) 之外，我們還將繼續在嗜酸性食道炎和伴有鼻息肉的慢性鼻竇炎的單獨 III 期研究中探索 TEZSPIRE，預計在今年下半年獲得頂線數據。

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, three of the eight 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 是一種一流的抗 OX40 單株抗體，其 ROCKET III 期研究計畫已成功招募超過 2,800 名中度至重度異位性皮膚炎患者。事實上，rocatinlimab ROCKET 研究計畫中的八項研究中，有三項目前已完全招募參與者。作為 ROCKET 計劃的一部分，第三階段 Horizo​​​​n 研究評估了 rocatinlimab 單藥治療與安慰劑對中度至重度異位性皮膚炎成人患者的療效，並有望在今年下半年獲得頂線數據。

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，我們還將繼續廣泛探索 rocatinlimab 在其他適應症中的應用，並已啟動針對中度至重度氣喘的 II 期研究，併計劃在今年下半年啟動針對結節性癢疹的 III 期研究。我們的罕見疾病研發管線的進展令我們感到鼓舞，並且擁有多個中後期研發機會。

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，我們預計今年將在重症肌無力和 IgG4 相關疾病方面獲得重要的 III 期數據，這兩種疾病都存在巨大的未滿足需求，我們有可能為患者帶來真正的改變。

Dazodalibep, an innovative CD40 ligand inhibitor fusion protein, has entered Phase III for Sjögren'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 CD40 配體抑制劑融合蛋白，已進入乾燥症的 III 期臨床試驗，目前有 2 項研究正在招募患者。先前，第二階段研究數據顯示，該藥物對中度至重度全身性疾病患者以及症狀負擔較重的患者俱有療效，令人鼓舞。 Dazodalibep 是第一個對後者患者群體證明有效的治療方法。

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 WEZENLA, our biosimilar candidate to STELARA, has received a positive CHMP opinion.

最後，在我們的生物相似藥產品組合中，我們已經啟動了 ABP 234（KEYTRUDA 的生物相似藥候選藥物）針對晚期或轉移性非鱗狀非小細胞肺癌患者的 III 期研究。我們也很高興地宣布，我們的 STELARA 生物相似藥候選藥物 WEZENLA 已獲得 CHMP 的正面評估。

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，我要感謝安進的同事們，感謝他們為面臨重症的患者表現出的強烈服務意識，以及他們致力於擴大我們的研究和業務對我們潛在的一流和最佳藥物組合的影響。現在我將把發言權交給 Murdo。

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 four 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。強勁的執行力使銷售額年增22%，我們業務的四大治療支柱的銷售量均實現強勁成長。我們在各地區實現了令人矚目的成長，其中 10 種產品實現了至少兩位數的銷售成長，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.

受銷售成長的推動，第一季我們的通用藥物業務（包括 Repatha、Prolia、EVENITY 和 Aimovig）的銷售額年增 18%。第一季度，Repatha 銷售額年增 33%，達到創紀錄的 5.17 億美元，目前 Repatha 正向價值數十億美元的企業邁進。本季度，我們的銷量年增了 44%，但淨售價下降了 13%，部分抵消了這一增長。

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其銷售成長。但為支持患者並擴大其就醫管道而提高回扣導致淨售價下降，在一定程度上抵消了這一影響。我們預計，擴大處方集覆蓋範圍以及取消多個付款人的事先授權要求將會導致心臟病專家和初級保健醫生更多地採用該技術。

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 本季的銷售額達到創紀錄的 3.42 億美元。在美國，銷售量成長得益於 EVENITY 處方量的擴大。在日本，EVENITY 繼續保持骨骼增強劑領域的領先地位，佔有 46% 的市場份額。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 在對抗這一風險方面具有令人興奮的成長潛力，我們將繼續運用我們在骨骼健康領域的成熟經驗，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-naïve patients with postmenopausal osteoporosis, who are at high risk of fracture.

Prolia 的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，再次證明了對於未經治療的停經後骨質疏鬆症高骨折風險患者而言，與阿崙膦酸鈉相比，Prolia 在降低骨折風險方面具有優勢。

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 的銷售額第一季同比增長了 1%。在美國，我們在本季初看到新患者數量強勁成長。今年 2 月和 3 月，Change Healthcare 的網路安全問題擾亂了這個體系，給一些試圖在專科藥房取藥的患者帶來了困難。

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量重新加速成長。鑑於 Otezla 的療效和安全性、出色的付款人覆蓋範圍和有限的事先授權要求，以及易於管理，我們認為 Otezla 未來具有巨大的成長潛力。為了實現這一潛力，我們增加了對皮膚病學現場力量和 Otezla 直接面向消費者媒體的投資，重點是努力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.

我也很高興 Otezla 最近獲得了兒科專營權，並被 FDA 批准用於治療 6 歲及以上患有中度至重度斑塊狀銀屑病且適合接受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.

第一季度，Enbrel 銷售額年減 2%，主要由於銷量下降，但庫存水準提高部分抵消了這一下降。展望未來，我們預期銷售量溫和成長但淨售價下降將抵銷其影響。 TEZSPIRE 持續保持強勁發展勢頭，第一季銷售額達 1.73 億美元。銷售額年增 80%，主要得益於預充式一次性注射筆的普及。

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。受銷量成長的推動，銷售額年增 122%。在美國，目前已有 2,000 多名醫療保健專業人員使用 TAVNEOS 治療了 3,000 多名患者。展望未來，我們將繼續利用我們在腎臟病學和發炎方面的專業知識，將 TAVNEOS 帶給更多 ANCA 的相關性血管炎患者。

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.

第一季度，我們的生物相似藥產品組合的銷售額年增 12%，但銷售成長被庫存水準下降和淨售價下降部分抵銷。我們預計，新分子的增加和更多產品的推出將推動生物相似藥業務的持續成長。

In Oncology, sales of our six 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，受銷售成長的推動，我們六種創新產品 BLINCYTO、LUMAKRAS、Vectibix、KYPROLIS、Nplate 和 XGEVA 的銷售額第一季年增 4%。第一季度，BLINCYTO 銷售額年增 26%，達到創紀錄的 2.44 億美元，這得益於學術界和社區對 B 細胞前體急性淋巴細胞白血病患者的廣泛處方。美國食品藥物管理局已將 PDUFA 日期定為今年 6 月 21 日，以決定是否批准 BLINCYTO 用於治療早期 CD19 陽性 B 細胞 ALL 患者。我們看到 BLINCYTO 在前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。我們看到 LUMAKRAS 未來的成長機會來自於新市場的推出和更多適應症。 Vectibix 的銷售額年增 6%，這得益於淨銷售價格上漲和銷量成長，但部分抵消了不利的外匯影響。 KYPROLIS 第一季銷售額年增 5%，達到創紀錄的 3.76 億美元，主要得益於美國以外地區的銷售成長。不包括 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 four 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.

我對我們本季的業績以及四大業務支柱的發展勢頭感到滿意。我們期待為世界各地更多受益於我們創新療法的患​​者提供服務。現在，我將把發言權交給維克拉姆 (Vikram)。

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，Murdo。我很高興提供有關罕見疾病的最新信息，罕見疾病是安進公司第四大增長治療支柱，該領域在第一季度實現了超過 9.5 億美元的產品銷售額。從用於治療甲狀腺眼疾（TED）的 TEPEZZA 開始，第一季的銷售額為 4.24 億美元，與傳統 Horizo​​n 業務的業績相比同比增長 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.

正如我們幾個月前在罕見疾病投資者會議上所討論的那樣，TED 通常使用臨床活動評分 (CAS) 進行評估，該評分涵蓋了許多不同的體徵和症狀，包括疼痛、發紅、腫脹和功能。我們現在根據高、低臨床活動評分或高、低 CAS 來指稱 TED。對於美國約 10 萬名可從 TEPEZZA 中受益的 TED 患者來說，其中大多數患者（約 80%）處於低 CAS 環境中。我們將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.

正如我們之前所討論的，在這種情況下，患者旅程中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% 的美國受保人制定了有利的醫療政策變化，我們預計這一勢頭將在 2024 年繼續保持。

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人員的覆蓋範圍，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，我們的重點是讓醫療保健提供者了解其對患者的重大影響，即使是對那些症狀不太明顯的患者。除了專注於培養眼科醫師和眼科醫師之外，我們還在加大對內分泌學的策略重點，並創造一支專門的銷售隊伍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 TEPEZZA 來說仍然是一個有意義的長期成長機會，該公司目前已獲得巴西和沙烏地阿拉伯的批准。提醒一下，今年一月份，我們向日本申請了高額 CAS 批准。我們針對低 CAS 的 III 期試驗正在繼續招募患者。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。我們啟動了第三階段皮下研究，並將此視為增加採用率和改善患者體驗的機會，為我們目前的靜脈注射配方提供替代選擇。

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 是一種用於治療慢性難治性痛風患者的藥物，第一季的銷售額達到 2.35 億美元，年成長 26%，這得益於強勁的商業執行帶來的銷量成長。 UPLIZNA 是 NMOSD 領域成長最快的生物製劑，第一季淨銷售額創下 8,000 萬美元的新高，年增 49%。 UPLIZNA 的國際擴張也正在進行中，目前已在美國以外的多個地區推出。包括加拿大在內的市場，該產品於今年 1 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、世界一流的製造和製程開發以及廣泛的全球影響力方面的領導地位，傳統 Horizo​​n 業務的整合繼續按計劃進行。現在我將把我們的財務更新交給彼得。

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 four 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。我們的強勁成長前景得益於我們四大治療支柱的創新產品線和市場產品組合，這些產品為全球嚴重疾病患者提供服務。在討論 2024 年指引之前，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 頁所示，第一季度，我們的總營收為 74 億美元，年增 22%。這反映了 25% 的銷售成長，其中包括來自收購的 Horizo​​​​n 產品和 Repatha、TEZSPIRE、EVENITY、Prolia 和 BLINCYTO 等主要品牌的超過 9 億美元。不計新增的Horizo​​n，產品銷售額年增6%，這得益於9%的銷售成長。

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.

我們的非公認會計準則營業費用上漲了 33%，反映了對 Horizo​​n 收購產品以及其他後期研發藥物（包括 rocatinlimab、MariTide 和 tarlatamab）的投資。因此，我們第一季的營業利潤率為 43%，與我們在第四季財報電話會議上的預期一致。我們的非公認會計準則 OI&E 導致支出 5.49 億美元，比去年同期增加了 3.34 億美元，這幾乎完全是由於收購 Horizo​​n 而發行的債務的利息支出增加，但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.

我們的非公認會計準則稅率年減 2.4 個百分點至 15.4%，這主要歸因於收益組合的變化、Horizo​​​​n 業務的納入以及本季度的淨有利項目。第一季度，該公司產生了 5 億美元的自由現金流，較上年的 7 億美元有所下降，這主要受到計劃向美國國稅局繳納 8 億美元稅款以停止不確定稅務狀況利息累積的影響，正如我們在第四季度財報電話會議上所討論的那樣。

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，當我們準備在今年晚些時候進行審判時，我們對我們的法律立場的信念沒有改變。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 整合工作正在順利進行中，我們預計在收購後第三年實現稅前 5 億美元的協同效應目標。我們還預計，到 2024 年底，我們的年度運行率將實現這一協同效應目標的約 50%。

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，並針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。我們將繼續致力於多項資本配置優先事項。我們繼續優先投資於內部和外部的最佳創新，並增加對後期項目的支出，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，我們將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工廠的產能。我們的北卡羅來納州工廠預計將於 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.

我們正在積極地在整個企業中整合生成式人工智慧，以引領創新並鞏固我們在行業中的領導地位。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 four quarters.

最後，我們在第一季支付了每股 2.25 美元的股息，向股東返還了資本。這比 2023 年四個季度支付的金額增加了 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 $19.00 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.

第 25 頁是 2024 年業務展望。在您對 2024 年剩餘時間進行建模時，我會提到一些考慮因素。我們根據對後期產品線的信心進行增量投資。

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, two PDUFA dates scheduled for June and five 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.

我們的研發投入體現了我們對創新的承諾，加速了我們的產品線建設，專注於推進多種潛在的同類首創和最佳藥物，包括支持 MariTide、定於 6 月進行的兩個 PDUFA 日期以及全年五次 III 期數據讀數。預計第二季和第三季非公認會計準則總營業費用將以與第一季相當的速度成長。自 2023 年 10 月初 Horizo​​n 交易完成以來，第四季度的費率將在 2023 年第四季與可比較的費用基數一起正常化。

We continue to anticipate our operating margin will improve over the next three 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 15.0% to 16.0%, 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我們的營業利潤率將會提高。我們預計 OI&E 約為 26 億美元，其中包括為收購 Horizo​​​​n 而籌集的 280 億美元債務相關的利息費用。我們預計非公認會計準則稅率在 15.0% 至 16.0% 之間，這主要受更有利的司法管轄收入組合推動，其中包括納入 Horizo​​​​n 業務相關的全年福利。我們的資本支出指引保持不變，2024 年約為 11 億美元。

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多位同事致力於服務病患。財務更新到此結束。現在我將把它交還給鮑勃，以便我們進行問答環節。

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，在您開始通話之前，請允許我指出，顯然，我們這裡有很多令人興奮的機會。我們對自己能夠為患者帶來改變的方法感到非常興奮。就肥胖症領域的機會而言，我們再次意識到，人們對此有濃厚的興趣。我們提供今天的更新，讓您了解我們在該領域的計劃。但我想重申，我們專注於成功完成並維護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，當我們進入問答環節時，請記住，除了我們在關於肥胖症和 MariTide 的準備好的評論中已經講過的內容之外，我們能說的內容將非常有限。但是考慮到這一點，朱利安，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.

（操作員指示）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?

關於 MariTide，鑑於已經進入第三階段，您能否提醒我們您希望在第二階段試驗中了解什麼以及可能在這裡了解到什麼，但這使您對未來的計劃充滿信心？

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

當然。 Salveen，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 Salveen 的提問。你看，我們受益於一項設計精良、執行良好的第二階段研究，這項研究可以讓我們了解很多關於這種藥物的知識，以及如何最佳地使用和接受這種藥物。我們從這些數據中看到了廣泛而差異化的概況，這將指導並鼓勵第三階段臨床研究。

Our next question comes from Michael Yee from Jefferies.

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?

我很感謝你的更新。我想我們都這樣。只是為了澄清或緩解任何投資者的擔憂，是否可以肯定地說，您的中期研究已經考慮了所有劑量，並且您覺得包括最高劑量和安全性指標（包括骨骼）在內的劑量都很安全？到目前為止，所有這些都已經被研究過了嗎？

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。我也要這個。再次，這是一項設計非常完善、執行非常良好的研究，並且充滿了測量數據。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，我們無法對個別特徵發表評論，但我們對迄今為止的結果非常滿意。我們正在快速推進第三階段計劃以及糖尿病第二階段計劃。我想重申的是，所有組別都保持活躍，到目前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 reviewed the data carefully.

我認為，邁克爾，正如傑伊所說，這是一項精心設計的研究，你可以確信我們仔細審查了數據。

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 Terence Flynn。

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。傑伊，您提到在 MariTide 上看到了差異化的概況。認識到你能說的話是有限的。但當我們思考差異化領域時，顯然是功效、耐受性和給藥間隔。所以只是想知道您是否可以評論一下您在哪些方面有所區分？那麼，您要尋找的基準是什麼？是司美魯肽、替澤帕肽，還是兩者皆有？

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，我們可以理解想要了解這一細節的願望。但也許，Murdo，你想談談競爭差異化嗎？然後傑伊，如果你覺得有什麼事情適合詳細闡述，你可以在 Murdo 之後加入。

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，我們正在密切關注市場上產品的差異化。我們也正在關注正在臨床開發的產品。在我們進入第二階段開發 MariTide 以及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產品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。我只想補充一點，特倫斯，這是一個非常令人興奮、充滿活力的領域。我們密切關注肥胖症藥物的發展。我認為在這種情況下，我們所採取的行動是不言而喻的。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.

下一個問題來自奧本海默公司的傑伊·奧爾森 (Jay Olson)。

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?

恭喜您取得的所有進展並感謝您提供最新消息。也許只是稍微轉向 tarlatamab。隨著潛在上市時間的迅速臨近，您能否談談為上市所做的準備工作，以及後期首次上市背後的策略，以及為擴大 tarlatamab 的形象和潛力而開展的臨床和商業工作？

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。也許，Murdo，你可以談談發射情況。然後我相信，傑伊，你想詳細說明這個臨床發展的想法。

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。傑伊，感謝您就我們產品組合中的另一款令人興奮的產品提出問題，我認為該產品將為小細胞肺癌患者帶來很多益處，小細胞肺癌是一種非常非常困難的診斷，而且幾乎沒有有效的治療方法能夠對小細胞肺癌產生任何持久的反應。因此，我們焦急地等待 FDA 的批准，但我們已經做好充分準備，並且在我們所有的現場組織中已經準備了一段時間。我們所有的現場人員，包括他們的醫療團隊，都經過了培訓並準備好了。

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，在獲得批准後很快就聯繫到治療醫生。我們非常清楚，要確保塔拉塔單抗獲得批准後能夠廣泛提供該藥物。我們對此感到非常高興。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，晚期患者的生存期非常悲慘，僅為數月。因此，我們有巨大的機會發揮影響力，我們不會浪費任何一分鐘、一小時或一天的時間來做這件事。

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 three Phase III studies.

傑伊，感謝您強調這種藥物的潛力，我們認為這是一個重大進步。自從我於 20 世紀 90 年代中期接受腫瘤科醫生培訓以來，這種疾病的治療方法實際上並未取得重大進展，採用先期化療，然後採用如今的 PD-L1 藥物進行免疫腫瘤治療，療效顯著但漸進。所以這就是時間過得不夠快以至於無法將這種藥物用於早期治療的情況。因此我們啟動了三項第三階段研究。

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，我將簡單介紹一下它們的架構。我們有一項研究將塔拉單抗與標準化療進行比較。這是針對第二線患者的研究，其主要終點是總體存活期，這項研究正在招募患者。我們確實希望讓這種藥物在前線治療中進行測試，正如你們所知，患者的病情進展非常快，以至於許多患者根本沒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，一項針對局限期小細胞肺癌，我們將研究在前期治療後立即使用塔拉塔單抗的貢獻。

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 three 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.

透過開發這些 BiTE 分子，我們了解到，在疾病治療過程中儘早使用它們會產生最佳效果。當我們進入前線時，所有人都遇到了這種情況。我們也了解到，當疾病負擔較低時，它們的效果最好。因此，這三項 III 期研究的設計將使這種藥物應用於更早期的患者治療。我想說的是，這個社區對此抱持著濃厚的興趣和巨大的希望。因此我們希望盡快進行這些研究。

Our next question comes from Mohit Bansal from Wells Fargo.

下一個問題來自富國銀行的 Mohit Bansal。

I have a question regarding the 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?

我對 AMG 133 的製造有疑問。當您踏上這段旅程時，您認為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 an 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，我認為我們不會懼怕製造或製程開發方面的挑戰。我認為，我們再次牢固確立了自己作為生物治療製造領域的世界領先地位。如您所知，這是一種基於抗體骨架的治療方法。所以對我們來說它就在球道的正中央。我們意識到，目前市場上的競爭對手已經很難維持這些藥品的供應，我相信患者也不會忘記這一點。

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.

我們決心竭盡全力，確保我們秉承每次在市場上為每位患者提供服務的悠久傳統。因此，我們再次認為，就我們需要解決的技術挑戰而言，這處於最佳狀態。我們認為——我們期待能夠做到這一點。正如我所說，我們每次都會保留對每位患者的記錄。

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.

至於你問的關於隨著時間的推移我們需要做什麼的問題，顯然，只要這變得有意義，Mohit，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，以讓我們為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.

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?

我將不再對你正在進行的審判抱持好奇心。但我會問這個問題。一、關於製造能力。我很好奇，您的目標是容納 100 萬到 200 萬名患者，還是 500 萬到 1000 萬名患者？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，顯然要知道你們有多少製造經驗和能力。其次，它是筆式設備嗎？我知道您提到它是一種“手持式、患者友好型、自動注射器”，只需一次注射。但是它是筆式設備還是其他東西？

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 Umer，我認為我們現在不會再談論交付——預期交付設備的任何事了。我認為我們已經盡可能清楚地表達了。我們認為這將對患者非常友好且方便。關於我們預期服務的患者數量，我們認識到這裡未滿足的需求非常大，我們希望能夠為那些我們認為對我們藥物的差異化特性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.

我想指出的是，我希望你們知道，今天我們已經在利用我們的生物療法為全球數百萬名患者提供服務。因此，我們再次向數百萬患者提供基於抗體的治療方法。我認為，目前全球 Prolia 患者數已達 800 萬人。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.

而且我相信大家都不會忘記，正如傑伊所說，給藥時間表可能是每月一次或更少，這意味著注射裝置的數量將遠遠少於競爭對手，例如，競爭對手實施的是每週一次的治療。所以，總而言之，我們了解您提出供應問題的原因。但我希望你們也能體認到我們有信心能夠應對這項挑戰的原因。

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

下一個問題來自 RBC Capital Markets 的 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.

也祝賀這些更新。我只是想問一下您的肥胖和心臟代謝策略。當然，有了有關 786 的消息，並且您談到 MariTide 在便利性方面的努力，既然您現在肯定以 MariTide 作為主要資產，那麼您如何考慮您投資組合中的口頭選擇？我只是好奇口頭選擇在長期內應如何與投資組合相適應。

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。而 786 的概況並沒有符合我們評估的標準。我們確實有一條管道，一條強大的早期資產管道。有基於腸促胰島素的，也有基於非腸促胰島素的。有些是注射的，有些是口服的。我們相信，市場存在異質性和多樣性——老實說，不同類型的患者需要治療肥胖症的藥物，而所有與肥胖相關的疾病都需要具有不同特性的藥物，我們正在努力實現這一目標。

Our next question comes from Tim Anderson from Wolfe Research.

我們的下一個問題來自 Wolfe Research 的蒂姆·安德森。

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，我想你應該能夠回答，那就是，你能否提醒我們，根據第一階段所展示的內容，你過去認為什麼是差異化？因此，我並不是要求您對最近看到的內容發表評論，而只是提醒您過去的評論，看看您覺得數據似乎顯示了什麼。當然，減少服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，我們對於什麼是市場差異化機會的看法一直相當一致，無論是在過去，還是在我們對這些結果的中期分析中。我們認為，我們擁有與 MariTide 實現差異化的廣闊機會。我的意思是，在多個方面呈現廣泛的差異化形象。我們始終相信，我們能夠憑藉差異化產品進入市場，將 MariTide 打造為解決尚未滿足的醫療需求的真正好機會，並在未來為數百萬患者提供治療服務。

Our next question comes from Yaron Werber from TD Cowen.

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——它本質上有點技術性。在 MariTide 的中期分析中，是否採用盲法？然後提醒我們，研究中是否有劑量滴定？

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。透過中期分析，作為研發領導者，我們能夠看到研究的指定治療部門。但重要的是，為了保持研究的完整性，這個中期分析對研究者和參與者來說是不公開的。

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

下一個問題來自美國銀行的 Geoff Meacham。

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 上還有另外一個。鑑於安進的心臟疾病產品組合和重點，您對將該項目擴展到糖尿病和肥胖症以外領域有什麼最新想法嗎？顯然，認識到您現在對安全性和耐受性概況有了更好的了解。

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。謝謝傑夫的提問和澄清。我們對 MariTide 的觀察以及我們對 MariTide 開發的計劃仍在繼續。我們正在為廣泛的第三階段計劃做準備，該計劃旨在解決肥胖症和多種肥胖相關疾病方面尚未滿足的需求，而且正如你所聽到的，還包括糖尿病方面的需求。

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

下一個問題來自 BMO 資本市場的 Evan Seigerman。

I'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?

儘管我很想在 MariTide 上詢問，但我不會這麼做。我實際上想問一個關於 rocatinlimab 的問題。那麼，隨著 Horizo​​​​n ROCKET 研究即將開始，您能否向我們講講您希望看到哪些差異？那麼，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.

兩件。也許傑伊可以從臨床角度談談分化問題。然後，在適當的範圍內，您可以開始思考如何定位 Murdo。

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，聽起來你已經接近完成這項工作了。但如你所知，rocatinlimab 是一種 OX40 定向單株抗體，無岩藻糖基化 IgG1，具有強的 ADCC。我們有一個名為 ROCKET 的項目，已有超過 2,800 名患者參與。因此，為了解決區分問題，我將把範圍限制在異位性皮膚炎領域。這裡是 HORIZON，即所謂的 HORIZON 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。實際入選患者有 726 名。在這種情況下，每 4 週使用一次 rocatinlimab，與安慰劑對照，並進行 24 週的治療讀數。我們的終點是16週和24週。我們會 — — 試驗之間的比較總是蘋果和橘子，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結果，具有強大的療效和出色的患者體驗和耐受性。在這裡，我們思考 Dupixent 並密切關注其發展工作。 Murdo，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-naïve. 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-naïve 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，我們正在研究廣大異位性皮膚炎患者。因此，我們將會有一些患者既有先前的生物學經驗，也有生物初次經驗。這樣我們就會知道如何在市場上有效地定位該產品。我只是——我可能會利用我們最近推出 TEZSPIRE 的經驗，並使用高度差異化的機制在不同適應症中與 Dupixent 進行區分，以及該領域的處方人員正在尋找對無反應患者和生物初治患者的替代方案的事實。因此，我們對這裡的機會感到很滿意。但顯然，我們必須等待數據並查看臨床試驗的讀數。

Our next question comes from Chris Schott from JP Morgan.

下一個問題來自摩根大通的克里斯·肖特 (Chris Schott)。

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?

您能否進一步詳細說明 TEZSPIRE 及其在第二階段資料後在 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計劃中看到的對不同嗜酸性粒細胞計數的療效，您期望在第三階段對這種化合物進行多廣泛的研究？

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 COPD 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呈現。由於作品及其摘要目前處於禁運狀態，我能分享的內容自然是有限的。但是，正如您以更機械的方式提問的那樣，我要提醒的是，TSLP 來自所謂的警報素家族。而他們所做的正是聽起來的那樣。

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、受刺激或被活化的上皮會釋放 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 細胞發炎環境中聚合，同時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.

慢性阻塞性肺病 (COPD) 的合理性與氣喘一樣強。但是如果你一定要知道的話，慢性阻塞性肺病 (COPD) 是一種比氣喘更具異質性的疾病。因此，本次臨床試驗的設計認識到並了解這一點，並在其中建立了一些預定義的分層進行分析，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。我們已經在這次隨機對照試驗中揭露了該分子具有臨床意義的活性。因此，請期待 ATS 的更多內容。您詢問的是更廣泛的發展。您說得對，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，我們有興趣在嗜酸性食道炎以及伴隨鼻息肉的慢性鼻竇炎中開發它。這兩種疾病在分子層面上都具有 2 型發炎的特徵。

Our next question comes from James Shin from Deutsche Bank.

下一個問題來自德意志銀行的 James Shin。

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.

這個有點超出預定範圍。這是給傑伊的，關於腫瘤學的。它適用於 AMG 651，即 EGFR CD3。只是想聽聽你對此的想法。我認為很快就會有一些數據出來，而且最近同行也會公佈一些其他數據。

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，我想這麼說，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，我們學會了調整與細胞表面抗原的結合效力以適應 CD3 的結合和活化程度。目前尚無新聞可以與您分享。我們將繼續研究這種藥物和其他針對實體腫瘤的 T 細胞結合雙特異性藥物，這確實受到了 tarlatamab 和 xaluritamig 的信心和指導的鼓舞。因此，我希望未來該藥物以及其他針對實體腫瘤的雙特異性 T 細胞抑制劑能有更多發展。

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 SubQ 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?

我對 TED 中的 TEPEZZA 有一個問題。您能談談您對這個 SubQ 計劃的進展嗎？我認為第三階段正在進行中。對此僅做一點點更新。當您繼續用 TED 治療更多患者時，您聽到了哪些有關安全問題的擔憂？這對吸收有影響嗎？

We'll take it in two 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.

我們將分兩部分來討論。傑伊，你可以解答臨床問題。然後，維克拉姆，如果你想分享關於市場的任何想法，請參與其中。

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。開發 TEPEZZA 的皮下給藥方法是安進研發部門在該專案中的首要任務。我們已經啟動第三階段的研究。這將是 — — 這是中度至重度活躍的 TED。該設計與我們迄今完成的靜脈標籤支持研究中所報告的設計類似。維克拉姆，如果你想談談臨床經驗。

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，我認為—感謝您的提問。我認為問題在於 AE 以及它是否限制了成長。我想，克里帕，您可能特別指的是聽力損失或有關聽力損失。

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.

因此讓我們從頂部開始。 TEPEZZA，它能非常有效地治療 TED，這是一種我們現在認為非常嚴重且使人衰弱的疾病。我們知道，IGF-1 與聽覺功能有關。因此，在 TEPEZZA 的臨床評估和臨床開發期間，我們非常仔細地觀察並評估了聽力功能。現在，我們已將其納入 PI 的警告和預防措施部分，並附有評估和監測的建議。這很重要，因為應該監測使用 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提高教育水準。雖然許多醫生確實使用基線聽力評估，但將其放入標籤中有助於標準化這種方法，好嗎？因此，在與 HCP 合作管理此問題之後，這通常不會成為發展的障礙，因為醫生通常了解 TEPEZZA 的有利風險效益狀況。

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。朱利安，我們已經到了指定的小時數了，但我們仍有幾個問題需要回答。因此，我們還需要花一些時間來嘗試解答您的問題。如果我們沒能聯繫到所有人，顯然，賈斯汀和他的團隊今晚將回答我們的任何問題。但是讓我們嘗試點擊這些，我們可以快速點擊它們，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?

我有一個 BLINCYTO，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。所以我只是想知道您是否有什麼計劃？或者您如何考慮在自體免疫領域開發 BLINCYTO 或其他 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.

感謝您的提問。憑藉著在 CD19 導向治療方面的深厚專業知識，以及在發炎和自體免疫方面的深厚專業知識，我們一直在密切關注這一領域，包括來自 CAR T 細胞療法的早期提示性證據，以及最近在系統性硬化症中報道的這項工作。正如您所說，看到 6 名患有相當難治的類風濕性關節炎的患者，真是令人興奮。所以你可以想像我們已經為抓住這個機會做好了充分的準備。我們發現這項工作非常鼓舞人心，未來我們將報告更多內容。

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

茱麗安，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來自 Raymond James 的 Gary Nachman。

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，我必須完成它。當您計劃進行第三階段研究時，您是否知道何時可以開始這些研究？它們有多大？與該領域的其他 III 期研究相比，其設計和整體時間表有何不同？以及您有什麼策略可以盡快加速這些研究，以及如何將美國和美國以外的研究結合在一起？在程序中？

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，我們現在將竭盡全力成功完成第二階段的研究，然後迅速與監管機構合作，就第三階段確定安全性和有效性的計劃達成一致，我們將盡快完成這項工作。我們認識到市場上仍然存在巨大的未滿足的需求，我們相信我們擁有可以幫助解決這個問題的資產。但是傑伊，我不知道您是否覺得可以說得更具體一些，但如果您可以說的話，請立即說。

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，我也是這麼想的，鮑伯。加里，如你所知，這是其中的一部分，收集監管機構正確預期的數據，並圍繞設計進行持續的討論。這項研究正在組織內盡可能快地推進——這個計畫正在組織內盡可能快地推進，你可以放心。

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，再次感謝大家參加電話會議，並重申如果你們有任何其他問題，賈斯汀和他的團隊將隨時為您服務。我們期待有機會在第二季度後的夏季與您交談，並提供有關我們預計從現在到那時在電話中提到的許多計劃所產生的信息流的最新信息。感謝您的關注。非常感謝。

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。