艾伯維 (ABBV) 2022 Q4 法說會逐字稿

Good morning. Thank you for standing by. Welcome to the AbbVie Fourth Quarter 2022 Earnings Conference Call. (Operator Instructions)

早上好。謝謝你的支持。歡迎來到 AbbVie 2022 年第四季度收益電話會議。 （操作員說明）

I would now like to turn -- introduce the call to Ms. Liz Shea, Senior Vice President of Investor Relations. You may proceed.

我現在想轉身 - 介紹投資者關係高級副總裁 Liz Shea 女士的電話。你可以繼續。

Good morning, and thanks for joining us. Also on the call with me today are Rick Gonzalez, Chairman of the Board and Chief Executive Officer; Rob Michael, Vice Chairman and President; Jeff Stewart, Executive Vice President, Chief Commercial Officer; Carrie Strom, Senior Vice President and President, Allergan Aesthetics; and Tom Hudson, Senior Vice President, R&D and Chief Scientific Officer. Joining us for the Q&A portion of the call are Scott Reents, Senior Vice President and Chief Financial Officer; and Roopal Thakkar, Vice President, Global Regulatory Affairs.

早上好，感謝您加入我們。今天與我通話的還有董事會主席兼首席執行官里克·岡薩雷斯 (Rick Gonzalez)； Rob Michael，副董事長兼總裁； Jeff Stewart，執行副總裁兼首席商務官； Allergan Aesthetics 高級副總裁兼總裁 Carrie Strom；以及研發高級副總裁兼首席科學官 Tom Hudson。與我們一起參加電話問答部分的是高級副總裁兼首席財務官 Scott Reents；和全球監管事務副總裁 Roopal Thakkar。

Before we get started, I'll note that some statements we make today may be considered forward-looking statements based on our current expectations. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Additional information about these risks and uncertainties is included in our SEC filings. AbbVie undertakes no obligation to update these forward-looking statements, except as required by law. On today's conference call, non-GAAP financial measures will be used to help investors understand AbbVie's business performance. These non-GAAP financial measures are reconciled with the comparable GAAP financial measures in our earnings release and regulatory filings from today, which can be found on our website. Following our prepared remarks, we'll take your questions.

在我們開始之前，我會指出，我們今天所做的一些聲明可能被視為基於我們當前預期的前瞻性聲明。艾伯維（AbbVie）警告說，這些前瞻性陳述受風險和不確定因素的影響，這些風險和不確定性可能導致實際結果與前瞻性陳述中所示的結果存在重大差異。我們向美國證券交易委員會提交的文件中包含有關這些風險和不確定性的更多信息。除法律要求外，艾伯維不承擔更新這些前瞻性陳述的義務。在今天的電話會議上，將使用非 GAAP 財務指標來幫助投資者了解 AbbVie 的經營業績。這些非 GAAP 財務措施與我們今天發布的收益報告和監管文件中的可比 GAAP 財務措施相一致，這些措施可以在我們的網站上找到。在我們準備好的評論之後，我們將回答您的問題。

So with that, I'll now turn the call over to Rick.

因此，我現在將電話轉給里克。

Thank you, Liz. Good morning, everyone, and thank you for joining us today. I'll provide perspective on our overall performance and outlook and then Jeff, Carrie, Tom and Rob will review our business highlights pipeline progress financial results and 2023 guidance in more detail. Today, we reported another strong quarter and a highly productive year for AbbVie. We delivered full year 2022 adjusted earnings per share of $13.77 reflecting double-digit growth. Total net revenues of more than $58 billion were up 5.1% on an operational basis, driven by impressive growth from SKYRIZI and RINVOQ, which generated nearly $7.7 billion of combined sales in 2022.

謝謝你，麗茲。大家早上好，感謝您今天加入我們。我將提供有關我們整體績效和前景的觀點，然後 Jeff、Carrie、Tom 和 Rob 將更詳細地審查我們的業務亮點管道進展財務結果和 2023 年指導。今天，我們報告了艾伯維又一個強勁的季度和高產的一年。我們實現了 2022 年全年調整後每股收益 13.77 美元，反映了兩位數的增長。在 SKYRIZI 和 RINVOQ 令人印象深刻的增長推動下，總淨收入超過 580 億美元，在運營基礎上增長了 5.1%，這兩家公司在 2022 年產生了近 77 億美元的合併銷售額。

As I reflect on our 10 years as an independent company, we have made excellent progress evolving AbbVie into a leading biopharmaceutical company. We have successfully created a well-diversified portfolio with multiple growth platforms in attractive and sustainable markets. This includes the rapid development and launch of SKYRIZI and RINVOQ across all of HUMIRA's major indications, plus a distinct new indication, atopic dermatitis. We anticipate these two products will collectively exceed the peak revenues achieved by HUMIRA by 2027 with significant growth expected through the end of the decade.

回顧我們作為一家獨立公司的 10 年，我們取得了卓越的進展，將 AbbVie 發展成為一家領先的生物製藥公司。我們已經在具有吸引力和可持續發展的市場中成功地創建了一個具有多個增長平台的多元化投資組合。這包括 SKYRIZI 和 RINVOQ 的快速開發和上市，涵蓋 HUMIRA 的所有主要適應症，以及一個獨特的新適應症——特應性皮炎。我們預計這兩種產品到 2027 年將共同超過 HUMIRA 實現的收入峰值，預計到本十年末將實現顯著增長。

We are also building a substantial portfolio of novel, heme and solid tumor assays for oncology. The anticipated launches and indication ramp of several new products like venetoclax in multiple myeloma and MDS, epacritumab across B-cell malignancies and Teliso-V, a new treatment option in non-small cell lung cancer will collectively support growth in the middle of the decade.

我們還在構建大量用於腫瘤學的新型血紅素和實體瘤檢測產品組合。幾種新產品的預期上市和適應症增加，如治療多發性骨髓瘤和 MDS 的維奈托克、治療 B 細胞惡性腫瘤的 epacritumab 和治療非小細胞肺癌的新選擇 Teliso-V，將共同支持本世紀中期的增長.

We expect continued robust performance in neuroscience with our leading on-market portfolio to address migraine and psychiatric conditions as well as a promising pipeline for neurodegenerative diseases. And we see significant long-term growth potential for aesthetics, an extremely attractive market, which is underpenetrated, where we have the leading position in toxins with Botox Cosmetic and Fillers with Juvederm. Second, we've established a productive innovation-driven R&D organization with a robust pipeline.

我們期望通過我們領先的市場產品組合在神經科學領域繼續保持強勁表現，以解決偏頭痛和精神疾病問題，並為神經退行性疾病提供有前景的管道。我們看到了美容的巨大長期增長潛力，這是一個極具吸引力的市場，但尚未充分滲透，我們在保妥適化妝品毒素和 Juvederm 填充劑方面處於領先地位。其次，我們已經建立了一個富有成效的創新驅動的研發組織，擁有強大的產品線。

Our R&D engine has discovered and developed five major billion-plus medicines over the past decade. We are committed to pursuing new ways to address patients' most serious health issues and have more than doubled our annual R&D investment since our inception. The breadth and the depth of our pipeline, which now includes more than 80 programs across all development stages, further supports our long-term growth outlook.

在過去十年中，我們的研發引擎發現並開發了五種主要的十億多藥物。我們致力於尋求新的方法來解決患者最嚴重的健康問題，並且自成立以來我們的年度研發投資增加了一倍以上。我們管道的廣度和深度，現在包括跨越所有開發階段的 80 多個項目，進一步支持我們的長期增長前景。

Lastly, we have maintained a strong financial position. to fully invest in innovative science and commercial initiatives across our therapeutic categories to drive long-term growth. We've also used that financial position to support a robust and growing dividend, which we have increased by 270% since our inception. And we have also used it as capacity to pursue value-enhancing business development to augment our existing portfolio and pipeline. With these strong operating characteristics, we remain well positioned to absorb the impact of the HUMIRA LLE and quickly return to robust sales growth in 2025.

最後，我們保持了強勁的財務狀況。全面投資於我們治療類別的創新科學和商業計劃，以推動長期增長。我們還利用這一財務狀況來支持強勁且不斷增長的股息，自成立以來我們已經增加了 270%。我們還利用它作為追求增值業務發展的能力，以擴大我們現有的產品組合和管道。憑藉這些強大的運營特點，我們仍處於有利地位，可以吸收 HUMIRA LLE 的影響，並在 2025 年迅速恢復強勁的銷售增長。

As it pertains to AbbVie's near-term outlook, we anticipate 2023 adjusted earnings per share of $10.70 to $11.10. This guidance range contemplates, we expected headwind from direct biosimilar competition with U.S. HUMIRA sales down approximately 37%, which is at the lower end of our previous erosion projection of 35% to 55%. Robust performance from SKYRIZI and RINVOQ, which we expect will collectively generate $11.1 billion of revenue, reflecting year-over-year growth of nearly 45%.

由於這與 AbbVie 的近期前景有關，我們預計 2023 年調整後的每股收益為 10.70 美元至 11.10 美元。考慮到這一指導範圍，我們預計與美國 HUMIRA 銷售額的直接生物仿製藥競爭帶來的不利影響將下降約 37%，這是我們之前預測的 35% 至 55% 的侵蝕率的下限。 SKYRIZI 和 RINVOQ 的強勁表現，我們預計它們將共同產生 111 億美元的收入，同比增長近 45%。

Revenue pressure in hem/onc with recent challenging market and share dynamics impacting Imbruvica, partially offset by strong sales growth of venetoclax. Double-digit revenue growth of neuroscience including accelerating sales of Vraylar with our recent MDD approval. Our guidance also contemplates the transient economic impact primarily in the U.S. on aesthetic procedure growth, affecting near-term performance for toxins, fillers and body contouring. Given that it's difficult to predict the duration of economic and inflationary pressures, we have not assumed the recovery in 2023.

Hem/onc 的收入壓力與近期具有挑戰性的市場和影響 Imbruvica 的股票動態，部分被 Venetoclax 的強勁銷售增長所抵消。神經科學的兩位數收入增長，包括在我們最近的 MDD 批准下加速 Vraylar 的銷售。我們的指南還考慮了主要在美國對美容程序增長的短暫經濟影響，影響毒素、填充劑和身體輪廓的近期表現。鑑於很難預測經濟和通脹壓力的持續時間，我們沒有假設 2023 年會出現復甦。

And finally, this guidance reflects increasing investments in both R&D and SG&A to support our long-term growth opportunities. It's also important to note that while it is possible 2023 could outperform our guidance, depending upon the shape of the HUMIRA erosion curve. We don't anticipate that 2024 earnings will be lower than the $10.70 floor of the 2023 adjusted earnings per share guidance, which we are issuing today. In summary, we are executing well across our business and see numerous opportunities for our diverse portfolio to drive long-term growth.

最後，該指南反映了對研發和 SG&A 的投資增加，以支持我們的長期增長機會。同樣重要的是要注意，雖然 2023 年可能會超過我們的指導，但這取決於 HUMIRA 侵蝕曲線的形狀。我們預計 2024 年的收益不會低於我們今天發布的 2023 年調整後每股收益指引的 10.70 美元下限。總而言之，我們在整個業務中表現良好，並看到我們多樣化的投資組合有很多機會來推動長期增長。

With that, I'll turn the call over to Jeff. Jeff?

有了這個，我會把電話轉給傑夫。傑夫？

Thank you, Rick. I'll start with the quarterly results for immunology, which delivered total revenues of more than $7.9 billion, up 19.5% on an operational basis. SKYRIZI and RINVOQ are performing exceptionally well, contributing more than $2.3 billion in combined sales this quarter, reflecting operational growth of 70%. SKYRIZI continues to exceed our expectations, outperforming our initial full year guidance by more than $750 million. Global revenues this quarter were nearly $1.6 billion, up 12.8% on a sequential basis.

謝謝你，里克。我將從免疫學的季度業績開始，它的總收入超過 79 億美元，在運營基礎上增長了 19.5%。 SKYRIZI 和 RINVOQ 表現異常出色，本季度貢獻了超過 23 億美元的合併銷售額，反映了 70% 的運營增長。 SKYRIZI 繼續超出我們的預期，超出我們最初的全年指導超過 7.5 億美元。本季度全球收入接近 16 億美元，環比增長 12.8%。

SKYRIZI is achieving strong market share momentum globally with in-play psoriatic disease leadership in 24 countries and total market share leadership in more than a dozen key markets. In psoriasis, SKYRIZI's total prescription share of the U.S. biologic psoriasis market has increased to more than 28%. And there is substantial room for continued growth in psoriasis based on SKYRIZI's leading in-play share of new and switching patients, which remains at nearly 50%.

SKYRIZI 在全球範圍內取得了強勁的市場份額勢頭，在 24 個國家處於銀屑病治療領域的領先地位，在十幾個主要市場的總市場份額處於領先地位。在銀屑病方面，SKYRIZI 在美國生物製劑銀屑病市場的總處方份額已增至 28% 以上。基於 SKYRIZI 在新患者和轉換患者中的領先在場份額（保持在近 50%），牛皮癬有很大的持續增長空間。

Psoriatic arthritis is also providing a nice inflection to SKYRIZI sales, especially in the U.S. Dermatology segment, where we have achieved approximately 10% share of the total biologic market. And we are also seeing encouraging SKYRIZI new patient starts in the U.S. room segment as well, which accounts for more than 80% of all PSA treatments. SKYRIZI is being co-positioned with RINVOQ to rheumatologists where these two products combined have already achieved a leading in-play PSA room share of approximately 16%.

銀屑病關節炎也為 SKYRIZI 的銷售提供了一個很好的轉折點，尤其是在美國皮膚科領域，我們在該領域的生物製劑市場份額已達到約 10%。我們也看到令人鼓舞的 SKYRIZI 新患者開始進入美國房間部分，佔所有 PSA 治療的 80% 以上。 SKYRIZI 與 RINVOQ 共同定位於風濕病學家，這兩種產品相結合已經實現了約 16% 的領先的 PSA 房間份額。

In Crohn's disease, we are making excellent progress with the U.S. launch. Feedback from gastroenterologists has been very positive, especially as it relates to SKYRIZI's novel dosing and overall clinical profile. We recently started DTC promotion for this indication and are already achieving a total in-play patient share of more than 15%.

在克羅恩病方面，我們在美國的上市取得了很好的進展。來自胃腸病學家的反饋非常積極，特別是因為它與 SKYRIZI 的新穎劑量和整體臨床概況有關。我們最近開始了針對該適應症的 DTC 推廣，並且已經實現了超過 15% 的在場患者總份額。

Turning now to RINVOQ which delivered global sales of $770 million, representing double-digit sequential growth. In rheumatology, global prescriptions are ramping nicely across RINVOQ's four approved indications; RA, PSA, ankylosing spondylitis and non-radiographic axial SpA. We continue to see positive market share momentum in both the U.S. and across key international geographies. In atopic dermatitis, RINVOQ is demonstrating strong uptake in both treatment-naive and second-line patients globally. Feedback from the global derm community supports the importance of RINVOQ as a long-term chronic therapy to control atopic dermatitis, especially as it relates to skin clearance and rapid itch relief. RINVOQ AD prescriptions are trending up globally with 20% to 35% in-place shares across our major international markets and a mid-teens in-place share in the U.S., which are both tracking in line with our expectations.

現在轉向 RINVOQ，它實現了 7.7 億美元的全球銷售額，實現了兩位數的環比增長。在風濕病學方面，全球處方在 RINVOQ 的四個已批准適應症中進展順利； RA、PSA、強直性脊柱炎和非放射學中軸 SpA。我們繼續看到美國和主要國際地區的市場份額增長勢頭。在特應性皮炎中，RINVOQ 在全球未接受治療的患者和二線患者中表現出強勁的吸收能力。來自全球 derm 社區的反饋支持 RINVOQ 作為控制特應性皮炎的長期慢性療法的重要性，特別是因為它與皮膚清除和快速止癢有關。 RINVOQ AD 處方藥在全球範圍內呈上升趨勢，在我們主要國際市場的現有份額為 20% 至 35%，在美國的現有份額為 20% 至 35%，這兩者都符合我們的預期。

In gastroenterology, the launch trends for RINVOQ in ulcerative colitis are very strong. Physicians have been pleased with RINVOQ's high rates of endoscopic healing as well as the speed of onset, which has quickly resulted in RINVOQ achieving approximately 20% in-play share in the U.S. second line plus setting. Internationally, RINVOQ UC is now approved in 50 countries with reimbursement discussions progressing in line with our expectations. This strong adoption in UC amongst gastroenterologists is very encouraging for RINVOQ's potential in Crohn's disease as well. We are on track for U.S. and EMA regulatory decisions in the second quarter and are preparing for the commercial launch.

在胃腸病學領域，RINVOQ 在潰瘍性結腸炎中的上市趨勢非常強勁。醫生對 RINVOQ 的高內窺鏡癒合率和起效速度感到滿意，這很快導致 RINVOQ 在美國二線加設置中獲得約 20% 的在場份額。在國際上，RINVOQ UC 現已在 50 個國家/地區獲得批准，報銷討論的進展符合我們的預期。胃腸病學家在 UC 中的這種強烈採用對於 RINVOQ 在克羅恩病中的潛力也非常令人鼓舞。我們正在為第二季度的美國和 EMA 監管決策做準備，並正在為商業發布做準備。

Global HUMIRA sales were approximately $5.6 billion, up 6% on an operational basis with 9.9% growth in the U.S. partially offset by international, where revenues were down 16.9% operationally due to biosimilar competition. In the U.S., we have secured broad formulary access for HUMIRA encompassing more than 90% of all covered lives, which enables us to compete for patient volume at parity to biosimilars.

全球 HUMIRA 銷售額約為 56 億美元，在運營基礎上增長 6%，其中美國增長 9.9%，部分被國際業務抵消，國際業務收入因生物仿製藥競爭而下降 16.9%。在美國，我們已經確保了 HUMIRA 的廣泛處方准入，涵蓋了所有覆蓋生命的 90% 以上，這使我們能夠與生物仿製藥同等地競爭患者數量。

Turning now to hematologic oncology, where total revenues were $1.6 billion, down 11.2% on an operational basis. Imbruvica global revenues were approximately $1.1 billion, down 19.5%. The U.S. performance continues to be impacted by challenging market and share dynamics attributed to the pace of COVID recovery as well as increasing competition. Venclexta global sales were $516 million, up 12.2% on an operational basis, with continued strong demand in both AML and CLL. We are particularly pleased with the international performance driven by robust share gains in the EU and across Asia.

現在轉向血液腫瘤學，其總收入為 16 億美元，在運營基礎上下降了 11.2%。 Imbruvica 全球收入約為 11 億美元，下降 19.5%。美國的表現繼續受到具有挑戰性的市場和股票動態的影響，這歸因於 COVID 復甦的步伐以及日益激烈的競爭。 Venclexta 全球銷售額為 5.16 億美元，在運營基礎上增長 12.2%，AML 和 CLL 的需求持續強勁。我們對歐盟和整個亞洲的強勁份額增長所推動的國際業績感到特別滿意。

In neuroscience, revenues were $1.7 billion, up 5.1% on an operational basis. Vraylar continues to demonstrate robust growth. Sales of $565 million were up 15.5% on an operational basis, reflecting increasing market share, primarily in Bipolar I Disorder. Vraylar was also recently approved as an adjunctive treatment for Major Depressive Disorder, marking its fourth approved indication and adding a new substantial opportunity for long-term growth.

在神經科學領域，收入為 17 億美元，在運營基礎上增長 5.1%。 Vraylar 繼續表現出強勁的增長。 5.65 億美元的銷售額在運營基礎上增長了 15.5%，反映了市場份額的增加，主要是在 I 型雙相情感障礙領域。 Vraylar 最近還被批准作為重度抑鬱症的輔助治療藥物，標誌著其第四個獲批的適應症，並為長期增長增加了新的實質性機會。

We are very pleased with the AMDD label, which confirms Vraylar's strong benefit risk profile, dosing flexibility with positive efficacy results for both the 1.5 and 3-milligram dose and the ability to reduce depressive symptoms as an add-on for the partial responders who present, and this is important, with or without symptoms of anxiety. The AMDD launch is off to a strong start, and we are already seeing a nice inflection in total new prescriptions in the marketplace.

我們對 AMDD 標籤感到非常滿意，它證實了 Vraylar 強大的效益風險狀況、1.5 和 3 毫克劑量的劑量靈活性和積極的療效結果，以及減少抑鬱症狀的能力，作為目前部分反應者的附加藥物，這很重要，無論是否有焦慮症狀。 AMDD 的推出有了一個良好的開端，我們已經看到市場上新處方的總數出現了很好的變化。

Within migraine, our leading oral CGRP portfolio contributed $249 million in combined sales this quarter, reflecting growth of nearly 30% as we continue to see strong prescription demand for both Ubrelvy and QULIPTA. We are also pursuing in the U.S. commercial approval for QULIPTA as a preventative treatment for patients with chronic migraine, which would further strengthen our competitive profile and uniquely position QULIPTA as the only oral CGRP available as a preventative treatment for patients with both chronic and episodic migraine.

在偏頭痛領域，我們領先的口服 CGRP 產品組合在本季度貢獻了 2.49 億美元的合併銷售額，反映出近 30% 的增長，因為我們繼續看到對 Ubrelvy 和 QULIPTA 的強勁處方需求。我們還在美國尋求 QULIPTA 作為慢性偏頭痛患者預防性治療的商業批准，這將進一步加強我們的競爭優勢，並將 QULIPTA 獨特地定位為唯一可用於慢性和發作性偏頭痛患者預防性治療的口服 CGRP .

Rounding out the migraine portfolio is Botox Therapeutic, a unique treatment with a dozen approved therapeutic indications and the clear branded leader in chronic migraine prevention. Total Botox Therapeutic sales were $728 million, up 10.7% on an operational basis. And last, we continue to prepare for the launch of ABBV-951 in both the U.S., Europe and Japan later this year. 951 represents a potentially transformative next-generation therapy for advanced Parkinson's disease and a $1 billion-plus peak sales opportunity. So overall, I'm pleased with the performance and the momentum across the therapeutic portfolio.

完善偏頭痛產品組合的還有 Botox Therapeutic，這是一種獨特的治療方法，具有十幾種經批准的治療適應症，並且是慢性偏頭痛預防領域明確的品牌領導者。 Botox Therapeutic 總銷售額為 7.28 億美元，在運營基礎上增長 10.7%。最後，我們繼續為今年晚些時候在美國、歐洲和日本推出 ABBV-951做準備。 951代表了晚期帕金森病的潛在變革性下一代療法和超過10億美元的銷售高峰期機會。總的來說，我對整個治療組合的表現和勢頭感到滿意。

And with that, I'll turn the call over to Carrie for additional comments on aesthetics. Carrie?

有了這個，我會把電話轉給嘉莉，徵求關於美學的更多評論。嘉莉？

Thank you, Jeff. Full year 2022, global aesthetic sales were approximately $5.3 billion, reflecting growth of 5% on an operational basis. Global Botox Cosmetic sales were approximately $2.6 billion, up nearly 21% operationally, and global Juvederm sales were approximately $1.4 billion, down roughly 2% operationally. Our global aesthetics portfolio grew in 2022 despite several headwinds, most notably inflationary dynamics in the U.S., COVID-related lockdowns in China and suspension of our operations in Russia.

謝謝你，傑夫。到 2022 年全年，全球美容銷售額約為 53 億美元，反映了運營基礎上 5% 的增長。全球保妥適化妝品銷售額約為 26 億美元，運營增長近 21%，喬雅登全球銷售額約為 14 億美元，運營下降約 2%。儘管存在一些不利因素，最顯著的是美國的通貨膨脹動態、中國與 COVID 相關的封鎖以及我們在俄羅斯的業務暫停，但我們的全球美學產品組合在 2022 年有所增長。

In the U.S. we began to see a slowdown in aesthetic procedures in the second quarter of last year, which coincided with the softening in economic metrics. These trends continued through the end of the year with the most significant impact on higher priced more deferrable procedures, including fillers and body contouring. Despite these economic pressures, U.S. Botox Cosmetic sales grew approximately 16% in 2022, driven by strong first half sales with growth moderating over the remainder of the year. Similarly, U.S. Juvederm saw strong growth in the first quarter of the year, but filler market declined throughout the second half of the year resulted in full year sales being down approximately 17% versus a robust 2021.

在美國，我們從去年第二季度開始看到美容程序放緩，這與經濟指標的疲軟相吻合。這些趨勢一直持續到年底，對價格更高且可延期的手術影響最大，包括填充劑和塑身術。儘管存在這些經濟壓力，美國保妥適化妝品銷售額在 2022 年增長了約 16%，這得益於上半年強勁的銷售額，而今年剩餘時間增長放緩。同樣，美國 Juvederm 在今年第一季度實現了強勁增長，但填料市場在整個下半年都在下滑，導致全年銷售額與強勁的 2021 年相比下降了約 17%。

We continue to track a number of key external economic metrics, including real personal consumption and the U.S. Consumer Confidence Index. While we have not seen major improvements in these metrics, data over the course of the last several months has shown stabilization. It remains difficult to predict the duration of these economic headwinds. But as Rick noted, we have modeled them to persist through the end of 2023. Our international aesthetics portfolio continued to demonstrate robust growth with the strong performance in most major markets, offsetting impacts from China and Russia.

我們繼續追踪一些關鍵的外部經濟指標，包括實際個人消費和美國消費者信心指數。雖然我們沒有看到這些指標有重大改善，但過去幾個月的數據顯示穩定。仍然很難預測這些經濟逆風的持續時間。但正如 Rick 指出的那樣，我們已將它們建模為將持續到 2023 年底。我們的國際美學產品組合繼續呈現強勁增長，在大多數主要市場表現強勁，抵消了來自中國和俄羅斯的影響。

International Botox Cosmetic sales of nearly $1 billion were up approximately 29% operationally and international Juvederm sales grew approximately 9% on an operational basis. We delivered this performance despite the significant headwinds we faced last year in our two largest international filler market, China and Russia. While our aesthetics portfolio in China continues to be impacted by COVID-related headwinds -- the current wave appears to have peaked. We expect the situation to improve through the first half of 2023 with full recovery in China beginning in the third quarter.

國際保妥適化妝品銷售額近 10 億美元，運營增長約 29%，國際喬雅登銷售額增長約 9%。儘管去年我們在兩個最大的國際填料市場中國和俄羅斯遇到了重大阻力，但我們仍取得了這一業績。雖然我們在中國的美學投資組合繼續受到與 COVID 相關的不利因素的影響，但目前的浪潮似乎已經見頂。我們預計情況會在 2023 年上半年有所改善，中國將從第三季度開始全面復甦。

Despite the transitory challenges we're facing, we remain confident in the long-term outlook for our aesthetics portfolio. Consumers continue to be very interested in the aesthetics category and in our brands. We see substantial room for further market penetration across each of our aesthetics categories and are continuing to invest to support long-term growth. Our promotional efforts are focused on driving more consumers into our customers' offices while increasing retention and productivity of existing patients.

儘管我們面臨著暫時的挑戰，但我們對我們的美學產品組合的長期前景仍然充滿信心。消費者繼續對美學類別和我們的品牌非常感興趣。我們看到在我們的每個美學類別中進一步市場滲透的巨大空間，並將繼續投資以支持長期增長。我們的促銷工作側重於吸引更多消費者進入我們客戶的辦公室，同時提高現有患者的保留率和生產力。

We have built a best-in-class commercial technology team known for developing our consumer loyalty program, Eli. We have over 5 million consumers who use Eli and more than 20,000 of our customers' offices. We have a series of new technology products launching this year to drive growth in the aesthetics market and support our customers and consumers. Internationally, we are focused on markets with significant growth potential. We have increased investments in injector training and expanded our field force in China, which is our second largest market. Latin America, which is very aesthetically oriented and Japan, which is growing rapidly and is expected to be one of our fastest-growing markets in 2023. Additionally, we are focused on delivering new product innovation.

我們建立了一流的商業技術團隊，以開發我們的消費者忠誠度計劃 Eli 而聞名。我們有超過 500 萬消費者使用 Eli 和 20,000 多個客戶辦公室。我們今年推出了一系列新技術產品，以推動美容市場的增長並支持我們的客戶和消費者。在國際上，我們專注於具有巨大增長潛力的市場。我們增加了對注射器培訓的投資，並擴大了在中國這個我們第二大市場的現場力量。非常注重審美的拉丁美洲和發展迅速的日本，預計將在 2023 年成為我們增長最快的市場之一。此外，我們還專注於提供新產品創新。

This year, we're launching two new fillers in the U.S., VOLUX for improvement of jawline, which was approved late last year and SkinVive for enhanced skin quality attributes, including hydration, which is expected to be approved in the first half of 2023. We're also continuing to launch HArmonyCa, our hybrid bio-stimulatory HA filler in several international markets.

今年，我們將在美國推出兩種新的填充劑，用於改善下巴輪廓的 VOLUX 已於去年年底獲得批准，而 SkinVive 用於增強皮膚質量屬性，包括水合作用，預計將於 2023 年上半年獲得批准。我們還將繼續在多個國際市場推出 HArmonyCa，這是我們的混合生物刺激性透明質酸填充劑。

The investments we're making to support long-term growth for our aesthetics portfolio, along with the stabilizing economic outlook and improving COVID dynamics in China, leave us well-positioned for future growth. With that, I'll turn the call over to Tom.

我們為支持我們的美學產品組合的長期增長而進行的投資，以及中國穩定的經濟前景和改善的 COVID 動態，使我們為未來的增長做好了準備。有了這個，我會把電話轉給湯姆。

Thank you, Carrie. We expect significant program advancement across all stages of our pipeline this year. In immunology, we continue to make very good progress with programs in our core diseases as well as in adjacent areas of rheumatology and dermatology, where we are expanding our portfolio.

謝謝你，嘉莉。我們預計今年我們管道的所有階段都會有重大的計劃進展。在免疫學方面，我們繼續在我們的核心疾病以及風濕病學和皮膚病學的鄰近領域取得很好的進展，我們正在這些領域擴大我們的產品組合。

We're nearing completion of SKYRIZI's registrational program in ulcerative colitis, which is the last major indication expansion program for SKYRIZI. In the first half of this year, we'll see data from the Phase III induction and maintenance studies for SKYRIZI in ulcerative colitis with our regulatory submissions anticipated later this year.

我們即將完成 SKYRIZI 在潰瘍性結腸炎方面的註冊計劃，這是 SKYRIZI 的最後一個主要適應症擴展計劃。今年上半年，我們將看到 SKYRIZI 治療潰瘍性結腸炎的 III 期誘導和維持研究的數據，我們預計將在今年晚些時候提交監管文件。

We'll also see data this year from our head-to-head comparison studies evaluating SKYRIZI versus other commonly used agents which we expect will further distinguish its profile from competitive offerings. These studies include our Phase III trial in Crohn's disease versus STELARA and our Phase III trial in psoriasis versus Otezla. Results from these studies will add to the body of evidence supporting SKYRIZI as a best-in-category agent in these indications.

我們今年還將看到來自我們對 SKYRIZI 與其他常用藥物進行評估的直接比較研究的數據，我們預計這將進一步將其與競爭產品區分開來。這些研究包括我們針對克羅恩病與 STELARA 的 III 期試驗以及我們針對銀屑病與 Otezla 的 III 期試驗。這些研究的結果將增加支持 SKYRIZI 作為這些適應症中同類最佳藥物的證據。

We're also nearing completion of the core indication expansion programs for RINVOQ. Our regulatory applications for RINVOQ and Crohn's disease are under review, and we anticipate approval decisions in the second quarter. RINVOQ demonstrated very strong rates of remission and endoscopic improvement in our Phase III induction and maintenance studies and we believe RINVOQ will be an important new treatment option once approved in Crohn's disease. This is a market where approximately 80% of bioexperience patients have used the TNF inhibitor, and there remains considerable unmet need for therapies that can deliver high rates of response and long-term remission.

我們也即將完成 RINVOQ 的核心適應症擴展計劃。我們對 RINVOQ 和克羅恩病的監管申請正在審查中，我們預計將在第二季度做出批准決定。 RINVOQ 在我們的 III 期誘導和維持研究中顯示出非常高的緩解率和內窺鏡改善率，我們相信一旦批准用於克羅恩病， RINVOQ 將成為一種重要的新治療選擇。在這個市場上，大約 80% 的生物體驗患者都使用過 TNF 抑製劑，並且對能夠提供高反應率和長期緩解的療法仍有相當大的未滿足需求。

Beyond our core immunology indications, we're developing RINVOQ in several diseases where we've seen strong evidence that our JAK inhibitor has the potential to become a highly effective therapy. Our Phase III program is already underway in one of these indications, giant cell arteritis. And later this year, we plan to begin Phase III studies for four additional diseases, systemic lupus, hidradenitis suppurativa, vitiligo and alopecia areata.

除了我們的核心免疫學適應症外，我們還在幾種疾病中開發 RINVOQ，我們已經看到強有力的證據表明我們的 JAK 抑製劑有可能成為一種高效的療法。我們的 III 期計劃已經在其中一項適應症中進行，即鉅細胞動脈炎。今年晚些時候，我們計劃開始針對另外四種疾病的 III 期研究，即係統性狼瘡、化膿性汗腺炎、白斑和斑禿。

Moving now to our oncology portfolio, where we expect several important regulatory and clinical milestones this year. In the area of hematology oncology, we'll see data from several Phase III studies, including results from Venclexta's event-driven de novo trial in relapsed/refractory multiple myeloma patients with a T114 mutation and Navitoclax' TRANSFORM-1 trial in frontline myelofibrosis. Results from these studies are expected to support regulatory submissions in the second half of the year for Venclexta and navitoclax in their respective indications.

現在轉到我們的腫瘤產品組合，我們預計今年會有幾個重要的監管和臨床里程碑。在血液腫瘤學領域，我們將看到幾項 III 期研究的數據，包括 Venclexta 在復發/難治性多發性骨髓瘤患者中進行的具有 T114 突變的事件驅動從頭試驗和 Navitoclax 在骨髓纖維化一線進行的 TRANSFORM-1 試驗的結果。這些研究的結果預計將在今年下半年支持 Venclexta 和 navitoclax 各自適應症的監管提交。

We also anticipate regulatory approval this year for epcoritamab in relapsed/refractory large B-cell lymphoma in several major geographies, including the U.S. in the second quarter and in Europe and Japan in the second half of the year. Based on the very deep and durable responses demonstrated thus far in our clinical program, we believe that epcoritamab has the potential to significantly improve upon treatment options for these patients.

我們還預計今年將在幾個主要地區批准 epcoritamab 治療復發/難治性大 B 細胞淋巴瘤，包括第二季度的美國以及今年下半年的歐洲和日本。基於迄今為止在我們的臨床項目中表現出的非常深刻和持久的反應，我們相信 epcoritamab 有可能顯著改善這些患者的治療選擇。

We believe that epcoritamab has the potential to become a core therapy for B-cell malignancies. And we continue to make very good progress, expanding our development programs for epcoritamab across several indications. Over the course of 2023, we expect to begin several new studies, including a Phase III study in frontline DLBCL in combination with R-CHOP and multiple Phase II studies in CLL and MCL. We remain very excited about epcroritumab's potential to become a best-in-class therapy across multiple B-cell malignancies and look forward to providing updates on these programs as the data mature.

我們相信 epcoritamab 有潛力成為 B 細胞惡性腫瘤的核心療法。我們繼續取得很好的進展，將我們的 epcoritamab 開發計劃擴展到多個適應症。在 2023 年期間，我們預計將開始多項新研究，包括前線 DLBCL 聯合 R-CHOP 的 III 期研究以及 CLL 和 MCL 的多項 II 期研究。我們仍然對 epcroritumab 成為多種 B 細胞惡性腫瘤的一流療法的潛力感到非常興奮，並期待隨著數據的成熟提供這些項目的更新。

Now moving to our solid tumor pipeline. We remain on track to see data later this year from our Phase II study evaluating Teliso-V in second-line plus advanced non-squamous non-small cell lung cancer. As a reminder, we received a breakthrough therapy designation for Teliso-V, our c-Met ADC, based on the encouraging results from Stage 1 of this Phase II study, and the data we'll see later this year has the potential to support an accelerated approval. Our Phase III confirmatory study in patients with overexpressed c-MET is also ongoing.

現在轉向我們的實體瘤管道。我們仍有望在今年晚些時候看到我們評估 Teliso-V 在二線和晚期非鱗狀非小細胞肺癌中的 II 期研究數據。提醒一下，我們的 c-Met ADC Teliso-V 獲得了突破性治療指定，這是基於該 II 期研究第一階段的令人鼓舞的結果，我們將在今年晚些時候看到的數據有可能支持加速批准。我們對過度表達 c-MET 的患者進行的 III 期驗證性研究也在進行中。

Treatment options for these cancer patients who have exhausted platinum-based chemotherapy, immunotherapy and targeted therapy are very limited and prognosis for these patients is extremely poor. As a targeted therapy for patients with overexpressed c-Met which represents approximately 25% of the non-squamous non-small cell lung cancer population, we believe Teliso-V has the potential to become an important new treatment option for these patients.

這些已經用盡鉑類化療、免疫療法和靶向療法的癌症患者的治療選擇非常有限，這些患者的預後極差。作為針對約佔非鱗狀非小細胞肺癌人群 25% 的 c-Met 過度表達患者的靶向治療，我們相信 Teliso-V 有潛力成為這些患者的重要新治療選擇。

We're also making good progress with our next-generation c-MET ADC, ABBV-400, which utilizes a more potent topoisomerase inhibitor payload, to potentially drive deeper tumor responses as well as broaden the range of solid tumors where c-MET therapies can be used such as gastroesophageal and colorectal tumors. We expect to see early data from our Phase I program in 2024.

我們的下一代 c-MET ADC ABBV-400 也取得了良好進展，它利用更有效的拓撲異構酶抑製劑有效載荷，有可能推動更深層次的腫瘤反應，並擴大 c-MET 治療的實體瘤範圍可用於胃食管和結直腸腫瘤等。我們希望在 2024 年看到第一階段項目的早期數據。

Elsewhere in the solid tumor pipeline, we have begun to see encouraging data from several programs which we plan to advance into Phase II studies this year. Our anti-GARP antibody, ABBV-151 is showing strong signals of activity, including deep responses with prolonged durability. Based on this preliminary efficacy, we plan to initiate Phase II studies in several tumor types. We also plan to advance ABBV-647 into Phase II dose optimizing studies this year based on the promising results from our early stage program. This ADC targets PTK7, which is a subset of non-squamous non-small cell lung cancer and represents approximately 25% of patients and has little overlap with c-Met. So our c-Met ADCs and PTK7 ADC combined will target approximately 45% of non-squamous non-small cell lung cancer patients.

在實體瘤管道的其他地方，我們已經開始看到來自我們計劃在今年推進到 II 期研究的幾個項目的令人鼓舞的數據。我們的抗 GARP 抗體 ABBV-151 顯示出強烈的活性信號，包括深度反應和持久性。基於這一初步療效，我們計劃在幾種腫瘤類型中啟動 II 期研究。我們還計劃根據我們早期項目的有希望的結果，將 ABBV-647 推進到今年的 II 期劑量優化研究。該 ADC 靶向 PTK7，它是非鱗狀非小細胞肺癌的一個子集，約佔患者的 25%，與 c-Met 幾乎沒有重疊。因此，我們的 c-Met ADC 和 PTK7 ADC 組合將針對大約 45% 的非鱗狀非小細胞肺癌患者。

Now moving to neuroscience, where we recently received FDA approval for Vraylar as an adjunctive treatment for Major Depressive Disorder, which marks its fourth indication approval. We're very excited by this approval and pleased with the label, which highlights Vraylar's strong benefit risk profile in this indication. Vraylar is an important new treatment option for patients who are currently taking an antidepressant but continue to have unresolved depression symptoms.

現在轉向神經科學，我們最近獲得 FDA 批准 Vraylar 作為重度抑鬱症的輔助治療，這標誌著它的第四個適應症批准。我們對這一批准感到非常興奮，並對標籤感到滿意，它突出了 Vraylar 在該適應症中的強大收益風險狀況。對於目前正在服用抗抑鬱藥但抑鬱症狀仍未解決的患者，Vraylar 是一種重要的新治療選擇。

We also recently received approval in Japan for ABBV-951, our novel subcutaneous levodopa carbidopa delivery system for treatment of advanced Parkinson's disease. This innovative approach to delivering DUOPA-like efficacy through a subcutaneous delivery system represents a potentially transformative improvement to current treatment options. With a less invasive, nonsurgical delivery system, it also has the potential to significantly expand the patient population currently addressed by DUOPA or other more invasive therapies for advanced PD patients such as deep brain stimulation. We remain on track for approval decisions this year in both the U.S. and Europe. In the U.S., we anticipate approval in the first half of the year, with product launch expected in the second half after we secure reimbursement.

我們最近還在日本獲得了 ABBV-951 的批准，這是我們用於治療晚期帕金森病的新型皮下左旋多巴卡比多巴輸送系統。這種通過皮下給藥系統提供類似 DUOPA 功效的創新方法代表了對當前治療方案的潛在變革性改進。憑藉侵入性較小的非手術輸送系統，它還有可能顯著擴大目前由 DUOPA 或其他針對晚期 PD 患者的侵入性更強的療法（如深部腦刺激）解決的患者群體。我們今年仍有望在美國和歐洲做出批准決定。在美國，我們預計在今年上半年獲得批准，並在我們獲得報銷後預計在下半年推出產品。

And in Europe, we anticipate approval in the fourth quarter of this year. And in the area of migraine, we remain on track for an FDA approval decision in the second quarter of this year for QULIPTA as a preventive treatment for patients with chronic migraine. In Europe, we anticipate an approval decision in the third quarter for atogepant as a preventive treatment for patients with both chronic and episodic migraine. If approved, this would be another differentiating feature for QULIPTA as it would be the only oral CGRP approved for prevention in patients with chronic migraine. This is a common and debilitating disease that significantly impacts quality of life and we look forward to make this new oral treatment option available to patients once approved.

在歐洲，我們預計將在今年第四季度獲得批准。在偏頭痛領域，我們仍有望在今年第二季度做出 FDA 批准 QULIPTA 作為慢性偏頭痛患者預防性治療的決定。在歐洲，我們預計第三季度將批准 atogepant 作為慢性和發作性偏頭痛患者的預防性治療。如果獲得批准，這將是 QULIPTA 的另一個區別特徵，因為它將是唯一被批准用於預防慢性偏頭痛患者的口服 CGRP。這是一種常見且使人衰弱的疾病，會嚴重影響生活質量，我們期待在獲得批准後為患者提供這種新的口服治療選擇。

And in our aesthetics pipeline, we expect to see results this year from several toxin programs including data from our Phase III study for Botox in platysma prominence with regulatory submission in the U.S. expected near the end of 2023 as well as data from our Phase III study for Botox in masseter muscle prominence, where we expect to submit regulatory applications in certain international markets in the second half of the year, including China and Canada. These two novel indications for prominent neck and jaw muscles will help to further build our portfolio in the lower face segment.

在我們的美學產品線中，我們預計今年會看到幾個毒素項目的結果，包括我們針對頸闊肌突出肉毒桿菌素的 III 期研究數據，預計將於 2023 年底在美國提交監管申請，以及我們的 III 期研究數據對於咬肌突出的保妥適，我們預計下半年將在某些國際市場提交監管申請，包括中國和加拿大。這兩個突出的頸部和下頜肌肉的新適應症將有助於進一步建立我們在下面部的產品組合。

We'll also see data from our Phase III trial for Bot-AE or short-acting toxin in glabellar lines near the end of this year with regulatory applications plan for 2024. So in summary, we continue to demonstrate significant progress across all stages of our pipeline and anticipate numerous important regulatory and clinical milestones again in 2023.

我們還將在今年年底看到眉間紋中 Bot-AE 或短效毒素的 III 期試驗數據，以及 2024 年的監管申請計劃。因此，總而言之，我們繼續在所有階段展示重大進展我們的管道並預計在 2023 年再次出現許多重要的監管和臨床里程碑。

With that, I'll turn the call over to Rob for additional comments on our fourth quarter performance and our 2023 financial outlook. Rob?

有了這個，我將把電話轉給 Rob，就我們第四季度的業績和 2023 年的財務前景發表更多評論。搶？

Thank you, Tom. AbbVie's performance and financial foundation remains strong with our leadership positions across a diverse portfolio, we are well-positioned to return to robust growth by 2025. Starting with fourth quarter results, we reported adjusted earnings per share of $3.60, which is $0.07 above our guidance midpoint.

謝謝你，湯姆。 AbbVie 的業績和財務基礎依然強勁，我們在多元化投資組合中處於領先地位，我們有能力在 2025 年之前恢復強勁增長。從第四季度業績開始，我們報告的調整後每股收益為 3.60 美元，比我們的指導高出 0.07 美元中點。

These results include a $0.13 unfavorable impact from acquired IPR&D expense. Total net revenues were $15.1 billion, up 3.8% on an operational basis, excluding a 2.2% unfavorable impact from foreign exchange. The adjusted operating margin ratio was 52.1% of sales. This includes adjusted gross margin of 86% of sales, adjusted R&D investment of 11.5% of sales, acquired IPR&D expense of 1.6% of sales and adjusted SG&A expense of 20.8% of sales. Net interest expense was $476 million, and the adjusted tax rate was 13.4%.

這些結果包括 0.13 美元的收購 IPR&D 費用的不利影響。淨收入總額為 151 億美元，在運營基礎上增長 3.8%，不包括外匯帶來的 2.2% 的不利影響。調整後的營業利潤率為銷售額的 52.1%。這包括調整後的毛利率佔銷售額的 86%、調整後的研發投資佔銷售額的 11.5%、收購的 IPR&D 費用佔銷售額的 1.6% 以及調整後的 SG&A 費用佔銷售額的 20.8%。淨利息支出為 4.76 億美元，調整後的稅率為 13.4%。

Turning to our financial outlook for 2023. Our full year adjusted earnings per share guidance is between $10.70 and $11.10. This earnings per share guidance does not include an estimate for acquired IPR&D expense that may be incurred throughout the year. We expect net revenues of approximately $52 billion. At current rates, we expect foreign exchange to have a neutral impact on full year sales growth.

轉向我們對 2023 年的財務展望。我們的全年調整後每股收益指引在 10.70 美元至 11.10 美元之間。本每股收益指引不包括對全年可能發生的收購 IPR&D 費用的估計。我們預計淨收入約為 520 億美元。按照目前的匯率，我們預計外匯對全年銷售增長的影響是中性的。

This revenue forecast comprehends the following approximate assumptions for our key products and therapeutic areas. We expect immunology sales of $24.8 billion, including SKYRIZI sales of $7.4 billion, reflecting growth of more than $2.2 billion due to strong market share performance across all approved indications. RINVOQ revenue of $3.7 billion, reflecting growth of more than 45% with continued indication expansion and HUMIRA sales of $13.7 billion, including U.S. erosion of 37% and following a loss of exclusivity in late January.

該收入預測包括以下對我們的主要產品和治療領域的近似假設。我們預計免疫學銷售額為 248 億美元，其中 SKYRIZI 銷售額為 74 億美元，反映出由於所有已批准適應症的強勁市場份額表現，增長超過 22 億美元。 RINVOQ 收入為 37 億美元，反映出隨著適應症的持續擴張和 HUMIRA 銷售額的增長超過 45%，銷售額為 137 億美元，其中包括美國侵蝕 37% 以及在 1 月下旬失去獨家經營權之後。

With one biosimilar currently in the market and potentially nine more biosimilars available in the middle of the year, we anticipate that sales erosion will be more heavily weighted towards the second half of 2023. In hematologic oncology, we expect Venclexta sales of $2.2 billion and Imbruvica revenue of $3.5 billion. For aesthetics, we expect sales of $5.2 billion, including $2.5 billion from Botox Cosmetic and $1.4 billion from Juvederm, with growth rates expected to improve when we lap the market slowdown in the middle of the year.

目前市場上有一種生物仿製藥，年中可能還會有 9 種生物仿製藥上市，我們預計到 2023 年下半年銷售下滑將更加嚴重。在血液腫瘤學方面，我們預計 Venclexta 銷售額為 22 億美元，Imbruvica收入 35 億美元。對於美容產品，我們預計銷售額為 52 億美元，其中包括 Botox Cosmetic 的 25 億美元和 Juvederm 的 14 億美元，預計年中市場放緩後增長率將會提高。

For neuroscience, we expect revenue of $7.2 billion representing growth of more than 10%, including Botox Therapeutic sales of $2.8 billion, Vraylar sales of $2.5 billion and total oral CGRP revenue of $1.1 billion, including Ubrelvy growth of approximately 17.5%. For eye care, we expect sales of $2.2 billion and we expect Mavyret revenue of $1.4 billion.

對於神經科學，我們預計收入為 72 億美元，增長超過 10%，包括 Botox Therapeutic 銷售額 28 億美元、Vraylar 銷售額 25 億美元和口服 CGRP 總收入 11 億美元，其中 Ubrelvy 增長約 17.5%。對於眼部護理，我們預計銷售額為 22 億美元，我們預計 Mavyret 的收入為 14 億美元。

Moving to the P&L for 2023. We are forecasting full year adjusted gross margin of 84% of sales, adjusted R&D investment of $6.8 billion and adjusted SG&A expense of $12.4 billion. We forecast an adjusted operating margin ratio of 47% of sales. This profile includes a 70 basis point benefit that is fully offset in tax expense given the transition of Puerto Rico's excise tax to an income tax effective at the beginning of this year. We expect adjusted net interest expense of $1.8 billion, and we forecast our non-GAAP tax rate to be 15.3%, including an impact of 1.3 points from the Puerto Rico tax transition. Finally, we expect our share count to be roughly flat to 2022.

轉到 2023 年的損益表。我們預測全年調整後的毛利率為銷售額的 84%，調整後的研發投資為 68 億美元，調整後的 SG&A 費用為 124 億美元。我們預計調整後的營業利潤率為銷售額的 47%。考慮到波多黎各的消費稅從今年年初開始向所得稅過渡，該概況包括 70 個基點的收益，該收益完全被稅收支出抵消。我們預計調整後的淨利息支出為 18 億美元，我們預計我們的非 GAAP 稅率為 15.3%，包括波多黎各稅收過渡帶來的 1.3 個百分點的影響。最後，我們預計我們的股票數量將大致持平到 2022 年。

Turning to the first quarter. We anticipate net revenues of $11.8 billion. At current rates, we expect foreign exchange to have a 1% unfavorable impact on sales growth. This revenue forecast comprehends the following approximate assumptions for our key therapeutic areas. Immunology sales of $5.5 billion, which includes U.S. HUMIRA erosion of 27%, Oncology revenue of $1.4 billion. Aesthetic sales approaching $1.2 billion; Neuroscience revenue of $1.5 billion; and eye care sales approaching $600 million.

轉到第一季度。我們預計淨收入為 118 億美元。按照目前的匯率，我們預計外匯會對銷售增長產生 1% 的不利影響。該收入預測包括以下對我們主要治療領域的近似假設。免疫學銷售額為 55 億美元，其中包括美國 HUMIRA 侵蝕 27%，腫瘤學收入為 14 億美元。美容銷售額接近 12 億美元；神經科學收入 15 億美元；眼部護理銷售額接近 6 億美元。

We are forecasting an adjusted operating margin ratio of 46% of sales, and we model a non-GAAP tax rate of 13.3%. We expect adjusted earnings per share between $2.39 and $2.49. This guidance does not include acquired IPR&D expense that may be incurred in the quarter.

我們預測調整後的營業利潤率為銷售額的 46%，我們將非 GAAP 稅率建模為 13.3%。我們預計調整後的每股收益在 2.39 美元至 2.49 美元之間。本指南不包括本季度可能發生的收購 IPR&D 費用。

Finally, AbbVie's strong business performance and outlook continues to support our capital allocation priorities. We expect to generate adjusted free cash flow of nearly $19 billion in 2023, which is net of $1.4 billion in SKYRIZI royalty payments. This cash flow will fully support a strong and growing dividend, which we have increased by 270% since inception, continued debt repayment, where we expect to pay down $4 billion in maturities this year bringing our cumulative debt reduction to $34 billion. Our strong cash flow also provides capacity for continued business development to further augment our portfolio. In closing, we are very pleased with AbbVie's strong results in 2022. And with our diverse portfolio, we continue to be well-positioned to deliver long-term growth.

最後，AbbVie 強勁的業務表現和前景繼續支持我們的資本配置優先事項。我們預計到 2023 年將產生近 190 億美元的調整後自由現金流，其中扣除了 14 億美元的 SKYRIZI 特許權使用費。這種現金流將充分支持強勁且不斷增長的股息，自成立以來我們已經增加了 270%，繼續償還債務，我們預計今年將償還 40 億美元的到期債務，使我們的累計債務減少額達到 340 億美元。我們強勁的現金流也為持續的業務發展提供了能力，以進一步擴大我們的投資組合。最後，我們對 AbbVie 在 2022 年取得的強勁業績感到非常高興。憑藉我們多元化的產品組合，我們將繼續處於有利地位以實現長期增長。

With that, I'll turn the call back over to Liz.

有了這個，我會把電話轉回給莉茲。

Thanks, Rob. We will now open the call for questions. (Operator Instructions). Operator?

謝謝，羅布。我們現在將開始提問。 （操作員說明）。操作員？

Our first question comes from Mohit Bansal with Wells Fargo.

我們的第一個問題來自 Wells Fargo 的 Mohit Bansal。

And so maybe a question -- a bigger question for Rick. So AbbVie -- when we talk to investors, AbbVie has always been one of those. The R&D as a percent of sales has always been low. And right now, even it is still less than 15%, and that's the pushback we get that the company cannot grow organically. And in some ways, you have always been playing defensive given that since inception, HUMIRA has always been an issue. Now that you're beginning to get past that, do you think something you'll change -- you'll want to change fundamentally with the company and the way you allocate internal versus external R&D spend? That would be very helpful.

所以也許是一個問題——對 Rick 來說是一個更大的問題。所以艾伯維——當我們與投資者交談時，艾伯維一直是其中之一。研發佔銷售額的百分比一直很低。而現在，即使它仍然不到 15%，這就是我們得到的公司無法有機增長的阻力。在某些方面，鑑於 HUMIRA 自成立以來一直是一個問題，您一直在採取防禦措施。既然你開始克服這個問題，你認為你會改變什麼——你會想要從根本上改變公司以及你分配內部與外部研發支出的方式嗎？那將非常有幫助。

Okay. This is Rick. So it's a good question. We've obviously heard that question. I think there's a number of dynamics that play into it when you look at our R&D expense as a profile. One is, obviously, we have a large volume of HUMIRA revenue that requires relatively little R&D support. And so that obviously dilutes out the profile of the business. As we see biosimilar impact, obviously, there will be some impact on that as HUMIRA revenues were to go down. The second thing is the aesthetics business, we're funding it aggressively to grow it. But by definition, it's not that expensive to be able to fund many of those programs. So it has a much lower profile. So some of it is mix when you think about it.

好的。這是瑞克。所以這是個好問題。我們顯然已經聽到了這個問題。當您將我們的研發費用視為概況時，我認為有許多動態因素在起作用。一個是，顯然，我們有大量的 HUMIRA 收入，需要相對較少的研發支持。因此，這顯然會稀釋業務的形象。正如我們所看到的生物仿製藥的影響，顯然，隨著 HUMIRA 收入的下降，這將受到一些影響。第二件事是美學業務，我們正在大力投資以發展它。但根據定義，能夠資助其中許多項目並不昂貴。所以它的知名度要低得多。因此，當您考慮時，其中一些是混合的。

The second thing I'd say is we obviously fund R&D at a level that we believe we can drive productivity. And I think if you look at our productivity over the last 10 years, the data I've seen suggests we are one of the most productive R&D engines in the industry. Certainly, when you look at products like SKYRIZI and RINVOQ, the return on those assets is tremendous.

我要說的第二件事是，我們顯然在我們認為可以提高生產力的水平上資助研發。我認為，如果你看看我們過去 10 年的生產力，我看到的數據表明我們是業內生產力最高的研發引擎之一。當然，當您查看 SKYRIZI 和 RINVOQ 等產品時，這些資產的回報是巨大的。

The third thing I'd say is, look, what drives R&D expense to the greatest extent is when you have large volumes of Phase III programs. And we're coming into a phase as we move forward over the next 3 or 4 years, where we have a number of programs that if they are successful, they will create a scenario where we will increase R&D. So an example of that would be our GARP program. We've seen some incredibly encouraging data out of that program thus far, it's a next-generation immuno-oncology program that combines with checkpoint inhibitors. And if that program continues to advance the way we see it now, we would want to expand our as our Phase II and then Phase III trials in that program significantly across the relatively broad range of solid tumors. That will require a significant increase in investment to be able to do that.

我要說的第三件事是，看，最大程度地推動研發費用的是當你有大量的 III 期項目時。隨著我們在未來 3 或 4 年內前進，我們將進入一個階段，我們有許多計劃，如果它們成功，它們將創造一個我們將增加研發的場景。因此，我們的 GARP 計劃就是一個例子。到目前為止，我們已經從該項目中看到了一些令人難以置信的令人鼓舞的數據，它是與檢查點抑製劑相結合的下一代免疫腫瘤學項目。如果該計劃繼續按照我們現在看到的方式推進，我們將希望在該計劃中擴大我們的 II 期和 III 期試驗，顯著涵蓋相對廣泛的實體瘤。這將需要顯著增加投資才能做到這一點。

So we tend to drive R&D based on programs that we have a high level of confidence, can be productive and can be successful. And we don't constrain R&D in any way from that perspective. Another program will be our Abeta program. If that program proves to deliver high rates of amyloid reduction and low ARIA, that will be another program that we want to rapidly move into Phase III.

因此，我們傾向於根據我們有高度信心、可以富有成效並且可以成功的項目來推動研發。從這個角度來看，我們不會以任何方式限制研發。另一個項目是我們的 Abeta 項目。如果該項目被證明能夠實現高澱粉樣蛋白減少率和低 ARIA，那將是我們希望迅速進入 III 期的另一個項目。

And so I can tell you, I'm very comfortable with the productivity we're getting out of R&D. Certainly, we will want to continue to increase that, and that's one of our objectives. We always look at programs on the outside to bring them in. And in fact, I'd say over the last couple of years, we've brought in a number of programs that are earlier stage programs. And we're fortunate from the standpoint that we have the ability to drive very strong growth, as we've indicated to investors between now and the end of this decade.

所以我可以告訴你，我對我們從研發中獲得的生產力感到非常滿意。當然，我們會希望繼續增加它，這是我們的目標之一。我們總是從外面看項目，以將它們引入。事實上，我想說在過去幾年中，我們引入了許多處於早期階段的項目。正如我們從現在到本十年末向投資者表明的那樣，從我們有能力推動非常強勁的增長的角度來看，我們是幸運的。

We can drive high single-digit growth. We're going to return to robust growth in '25. So we're looking mostly for assets that will allow us to drive growth in that late 20s and early 30s time frame. So again, as those mature and they're successful, and they go into later-stage development programs, they will drive further need for investment.

我們可以推動高個位數的增長。我們將在 25 年恢復強勁增長。因此，我們主要尋找能夠讓我們在 20 年代末和 30 年代初的時間框架內推動增長的資產。因此，隨著那些人的成熟和成功，他們進入後期開發計劃，他們將再次推動對投資的進一步需求。

Mohit, this is Rob. I'll just add that. If you look at this year's guide, it's a great example of our willingness to increase R&D investment where it's needed. So if you look at we're increasing it from $6.4 billion to $6.8 billion. Those increases are focused on epcoritamab as well as midstage assets such as GARP and PTK7. We also have several new Phase III studies for additional RINVOQ indications, which could contribute several billion dollars of revenue in the latter half of the decade. So even in the year where we're seeing a decline in the top line, we're increasing R&D investments. We're very committed to increasing innovation investment, whether it's internal or external.

莫希特，這是羅布。我會補充一點。如果你看一下今年的指南，它就是一個很好的例子，表明我們願意在需要的地方增加研發投資。因此，如果您看一下我們將其從 64 億美元增加到 68 億美元。這些增長集中在 epcoritamab 以及中期資產，如 GARP 和 PTK7。我們還針對其他 RINVOQ 適應症進行了幾項新的 III 期研究，這可能會在本世紀後半葉貢獻數十億美元的收入。因此，即使在我們看到收入下降的那一年，我們也在增加研發投資。我們非常致力於增加創新投資，無論是內部還是外部。

Our next question is from Terence Flynn with Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Terence Flynn。

I guess, I just wondered, high level, if there was anything different, Rick, or Rob, about your approach to guidance on the revenue side this year versus last year. I think last year, performance was choppy across a number of different franchises. So as you thought about the guidance this year, anything different as you approached it?

我想，我只是想知道，高層，Rick 或 Rob，關於你們今年在收入方面的指導方法與去年相比是否有什麼不同。我認為去年，許多不同特許經營權的表現起伏不定。所以當你考慮今年的指南時，你接近它時有什麼不同嗎？

And then my second question is any other details you can provide on how you're thinking about HUMIRA in 2024? Obviously, I appreciate the color this year, but how should we think about 2024 dynamics in the U.S.

然後我的第二個問題是你可以提供關於你如何看待 2024 年 HUMIRA 的任何其他細節？顯然，我很欣賞今年的顏色，但我們應該如何看待美國 2024 年的動態？

Okay. So maybe I'll start, and then Rob can fill in anything that I might miss. I think whenever we look at guidance, we look at it -- and I think this has been our historical practice. We obviously look at guidance as something that we have a very high level that we can execute against that guidance. I would say this year, you've seen that the range is a little bit wider than what we normally project. And we did that based on the fact that as HUMIRA goes biosimilar, obviously, very small changes in the assumptions we're making on erosion for HUMIRA can have a fairly significant impact. So we're right in the range by about $0.10. and that's reflected in this guidance.

好的。所以也許我會開始，然後 Rob 可以填寫任何我可能遺漏的內容。我認為每當我們查看指導時，我們都會查看它——我認為這一直是我們的歷史慣例。顯然，我們將指導視為我們可以根據該指導執行的非常高的水平。我會說今年，你已經看到範圍比我們通常預測的要寬一點。我們這樣做是基於這樣一個事實，即隨著 HUMIRA 走向生物仿製藥，顯然，我們對 HUMIRA 侵蝕所做的假設的微小變化可能會產生相當大的影響。所以我們在大約 0.10 美元的範圍內。這反映在本指南中。

And so I would say that as we have in -- historically, we have a high level of confidence we're going to deliver on this guidance. As it relates to 2024, we have provided as part of this guidance, what we are projecting to be a floor because we've gotten a lot of requests from investors about when will we hit the trough and will it be '23 or will it be '24? So maybe to give you a little color around how we think about that. One, the $10.70 is a floor. That doesn't mean that we will go down to $10.70.But it means that we would say to investors that, that's what you should assume is the absolute floor. Now when will that floor if it were to occur, when will it occur? Will we see the trough in 2023? Or will we see the trough in 2024?

因此，我想說的是，正如我們所擁有的——從歷史上看，我們對實現這一指導意見充滿信心。與 2024 年相關，作為本指南的一部分，我們提供了我們預計的底線，因為我們收到了投資者的很多請求，詢問我們什麼時候會觸底，會是 23 年還是會24歲？因此，也許可以讓您了解一下我們對此的看法。第一，10.70 美元是一個底線。這並不意味著我們會跌至 10.70 美元。但這意味著我們要對投資者說，這就是你應該假設的絕對下限。現在，如果它要發生，那層樓什麼時候發生，它什麼時候發生？我們會在 2023 年看到谷底嗎？或者我們會在 2024 年看到低谷嗎？

And I would tell you that our expectations would be based on this plan, the trough should occur in 2023. But what I would tell you is if we significantly overachieved this plan into 2023, and there's obviously somewhat greater risk it could move into '24. The reason why it is in '23 versus '24 based on our current planning assumptions, is because the strength of the growth platform has the ability between where it will grow in '23 and where it will grow in '24 to offset what will obviously be further erosion of HUMIRA in 2024. 2024, you will basically have to impacts on HUMIRA. You will have the annualization of this year. And as Rob said in his remarks, we expect more of an impact in the second half of '23.

我會告訴你，我們的預期將基於這個計劃，谷底應該出現在 2023 年。但我要告訴你的是，如果我們在 2023 年大大超額完成了這個計劃，那麼進入 24 年的風險顯然會更大.根據我們目前的規劃假設，它在 23 年與 24 年相比，是因為增長平台的實力有能力在 23 年和 24 年的增長之間抵消明顯的增長到 2024 年 HUMIRA 將進一步受到侵蝕。2024 年，你基本上將不得不對 HUMIRA 產生影響。你會有今年的年化。正如 Rob 在他的評論中所說，我們預計在 23 年下半年會產生更大的影響。

So when you annualize that, you're going to have an impact that flows through to '24. And then we would expect further erosion of HUMIRA, both price and probably to a greater extent, volume in 2024. But the growth platform has the ability to grow through that based on those assumptions. And so that's the philosophy that we operate with on the guidance. Rob, anything you'd add?

因此，當您將其年化時，您將產生影響到 24 年。然後我們預計到 2024 年 HUMIRA 的價格和銷量可能會進一步下降。但增長平台有能力根據這些假設實現增長。這就是我們在指南中所遵循的理念。羅伯，你有什麼要補充的嗎？

I think if you reflect back on the history of AbbVie, we've had a long track record at delivering exceeding our guidance. I think 2022 is an exception. And if you look at on the top line now, we didn't make earnings. So that's important to highlight. If you look at the top line, the two biggest factors that drove the miss versus original guidance in 2022 were with Imbruvica and Venclexta, the CLO market, we did not anticipate that, that market would actually not recover. I mean that's -- it's down 20% versus pre-pandemic levels. And then we did see some additional share impact on Imbruvica.

我認為，如果你回顧一下 AbbVie 的歷史，我們在超越我們的指導方面有著悠久的記錄。我認為 2022 年是個例外。如果你看看現在的收入，我們沒有盈利。所以強調這一點很重要。如果你看看最高線，導致 2022 年偏離最初指導的兩個最大因素是 Imbruvica 和 Venclexta，CLO 市場，我們沒有預料到，該市場實際上不會復蘇。我的意思是——與大流行前的水平相比下降了 20%。然後我們確實看到了對 Imbruvica 的一些額外的份額影響。

And then aesthetics, we saw, obviously, in the month of May, we started to see a slowdown in the economy. We had a very strong first quarter. So both of those things really are what drove the top line miss, we made earnings. Now we have factored both those things in the 2023 guidance to give investors confidence that we said it appropriately. But we always look to set the most responsible guidance we can, and we feel good about where we set 2023.

然後是美學，我們顯然在 5 月份看到，我們開始看到經濟放緩。我們有一個非常強勁的第一季度。因此，這兩件事確實是導致頂線失利的原因，我們獲得了收益。現在，我們已在 2023 年指南中考慮了這兩件事，讓投資者相信我們說得對。但我們始終希望盡我們所能製定最負責任的指導方針，我們對 2023 年的設定感到滿意。

It comes -- our next question comes from Chris Schott with JPMorgan.

它來了 - 我們的下一個問題來自摩根大通的克里斯肖特。

Just two for me. Maybe just following up on the 2023 guidance being a trough number. It seems like you're still going to have about a $12 billion U.S. HUMIRA franchise here. So can you just provide maybe a little bit more color of what you're envisioning 2024 to look like for HUMIRA? Like is it reasonable to think about the down 35% to 40% year as we look out to '24. I think we want to make sure to get our hands around just the -- how much growth in that core platform and how much of a headwind, I guess, HUMIRA is going to be facing at the same time.

對我來說只有兩個。也許只是跟進 2023 年的指導是一個低谷數字。看起來你在這裡仍將擁有約 120 億美元的美國 HUMIRA 特許經營權。那麼，您能否提供更多關於 HUMIRA 到 2024 年的設想的顏色？當我們展望 24 年時，考慮下降 35% 到 40% 的年份是否合理。我認為我們希望確保掌握——我想 HUMIRA 將同時面臨該核心平台的增長量和逆風量。

My second question was just on aesthetics trends as we move through this year. You've talked about some signs of at least sequential stability the last few quarters. You're talking about stepping up investments. You've got a couple of new products launching. I guess why shouldn't we think about some recovery in this business as we look out to the second half of the year?

我的第二個問題只是關於我們今年的美學趨勢。在過去的幾個季度中，您談到了至少連續穩定的一些跡象。你在談論加強投資。你有幾個新產品發布。我想為什麼我們不應該在展望下半年時考慮這項業務的複蘇？

Chris, this is Rick. Let me talk a little bit about HUMIRA and the trough. We're 2 weeks into the biosimilar activity. So it's a little difficult to give you precise predictions for 2024. I think the way to think about HUMIRA going forward is what we would expect is the most significant impact on HUMIRA is going to be price. And obviously, we're trying to predict going forward what that price will look like. Certainly, as we look at this year, the most significant impact is clearly price. So that's more predictable because we obviously know what the pricing is in the contracts that we've put together. And so I think that's something that we have a high level of confidence.

克里斯，這是里克。讓我談談 HUMIRA 和槽。我們已經進行了 2 週的生物仿製藥活動。因此，很難對 2024 年做出準確的預測。我認為考慮 HUMIRA 未來發展的方式是我們所期望的，對 HUMIRA 最重要的影響將是價格。顯然，我們正試圖預測未來的價格會是什麼樣子。當然，就我們今年而言，最重要的影響顯然是價格。所以這更可預測，因為我們顯然知道我們制定的合同中的定價是多少。所以我認為這是我們非常有信心的事情。

There will be further pressure on price as we move into '24, and there'll probably be further pressure on volume in '24. But I would say, at the end of '24, I would expect HUMIRA to start to develop a more stable tail of revenue. It will still have some pressure as we move in '25, but '25 and '26 is where we should see that more stable tail for HUMIRA emerge. And that's one of the things that allows us to be able to see the underlying growth from the growth platform. So a number of things happen between '23 and '24 and then '25 as we move forward.

隨著我們進入 24 世紀，價格將面臨進一步的壓力，24 年的交易量可能會面臨進一步的壓力。但我會說，在 24 年底，我預計 HUMIRA 將開始開發更穩定的收入尾巴。隨著我們在 25 年的發展，它仍然會有一些壓力，但是 25 年和 26 年我們應該看到 HUMIRA 出現更穩定的尾巴。這是讓我們能夠從增長平台看到潛在增長的原因之一。因此，隨著我們前進，在 23 年和 24 年之間以及 25 年之間發生了很多事情。

As you mentioned in your second comment, we would certainly expect that the U.S. economy will start to recover in '24. It may recover earlier than that. And if it does, that would be great. We don't want to put a plan together to assume that because obviously, that's difficult for us to predict. But I think we would all expect that '24 will see a recovery in the U.S. economy. And we would fully expect for the aesthetics business to return back to historical growth rates very quickly when that happens. And so that will be another opportunity for that business to be able to grow. And then I would say Imbruvica is the other key issue for us as we move forward. We would expect the majority of the erosion that we see on Imbruvica will occur this year, and there will be less downward pressure as we move to '24.

正如您在第二條評論中提到的，我們當然預計美國經濟將在 24 世紀開始復蘇。它可能會比這更早恢復。如果確實如此，那就太好了。我們不想制定一個計劃來假設這一點，因為顯然，這對我們來說很難預測。但我認為我們都希望 24 世紀美國經濟會復蘇。當這種情況發生時，我們完全希望美容業務能夠很快恢復到歷史增長率。因此，這將是該業務發展的另一個機會。然後我會說 Imbruvica 是我們前進的另一個關鍵問題。我們預計，我們在 Imbruvica 上看到的大部分侵蝕將發生在今年，並且隨著我們進入 24 年，下行壓力將會減少。

So that's what allows the growth to be able to come up. What I would tell you even though I don't want to make a prediction in '24 of what HUMIRA will look like. I think we have a high level of confidence that we have the ability if the erosion curve looks like how we've modeled it now between '23 and '24 then we have the ability to be able to have the growth platform and go through that. So we can absorb that impact. And so far, like I said, it's early on, but I'd say so far, we're comfortable with how things are playing out.

所以這就是允許增長能夠出現的原因。儘管我不想在 24 年預測 HUMIRA 的外觀，但我會告訴您的內容。我認為我們有很高的信心，如果侵蝕曲線看起來像我們現在在 23 年到 24 年之間建模的那樣，那麼我們就有能力擁有增長平台並通過它.所以我們可以吸收這種影響。到目前為止，就像我說的那樣，它還很早，但我想說到目前為止，我們對事情的進展感到滿意。

Rob, anything you want to add on the first question, and Carrie, maybe you can give a little more color.

Rob，你想在第一個問題上添加任何內容，Carrie，也許你可以提供更多顏色。

I think you characterized it well, Rick. I mean the thing to highlight for this year for '23, the way you think about HUMIRA really in the first half of the year, the vast majority of that erosion will be priced. In the second half, you'll see because we've contracted rebates, you'll see a step-up in the price erosion, although you also will see more volume with biosimilars coming in the market in the middle of the year, we would expect more volume erosion. I think as we think about '24, we would expect, based on the contract to see a step up in price, but albeit not at the same level as we see in '23, but '24 would be more volume. It's probably the best way to think about it right now. We're not going to give you guidance, but if you think about how to model HUMIRA '23, '24, that's the way to think through it.

我認為你很好地描述了它，里克。我的意思是今年 23 年要強調的事情，你在今年上半年真正考慮 HUMIRA 的方式，絕大多數侵蝕都將被定價。在下半年，你會看到，因為我們已經簽訂了回扣合同，你會看到價格下跌的步伐加快，儘管你也會看到今年年中市場上的生物仿製藥數量增加，我們預計會有更多的體積侵蝕。我認為，當我們考慮 24 年時，我們預計，根據合同，價格會上漲，但儘管與我們在 23 年看到的水平不同，但 24 年的數量會更多。這可能是現在考慮它的最佳方式。我們不會給你指導，但如果你考慮如何為 HUMIRA '23、'24 建模，那就是思考的方式。

Okay. Carrie, anything you want to add on asesthetics?

好的。嘉莉，你想在美學上添加什麼？

Yes. This is Carrie. The -- in terms of the aesthetics market and how we're thinking about it for 2023, I mean, first, I'd say, yes, this is still a very strong fundamental market with consumers who are very interested in entering the category. And so that remains a strong opportunity the now and in the future.

是的。這是嘉莉。就美學市場以及我們對 2023 年的看法而言，我的意思是，首先，我想說，是的，這仍然是一個非常強大的基本市場，消費者對進入該類別非常感興趣.因此，這在現在和未來仍然是一個很好的機會。

But what we saw as we exited 2022 is as these economic metrics were softening, we also saw that reflected in demand for aesthetic procedures. And in our conversations with customers, we saw that reflected in their practices, market research with consumers, where they said, yes, we're interested in the category, but we want to see what's going on with the economy, perhaps before a new patient might want to enter the category. And based on that, we are modeling for those trends to continue in 2023.

但我們在 2022 年結束時看到的是，這些經濟指標正在走軟，我們也看到這反映在對美容程序的需求上。在我們與客戶的對話中，我們看到這反映在他們的做法、與消費者的市場研究中，他們說，是的，我們對該類別感興趣，但我們想看看經濟的發展情況，也許在新的患者可能想輸入該類別。基於此，我們正在為這些趨勢在 2023 年繼續進行建模。

And what that means for U.S. toxin market is the market growth would be around a mid-single-digit decline, for U.S. filler market around a 10% decline. And like we said, those growth rates would be different by quarter as we lap a strong first part of the year. Now of course, if there is a scenario like a deep recession, where unemployment skyrockets, that is not something that we've contemplated. Or on the other hand, if the macroeconomic environment stabilizes or improves that would represent favorability to our plan.

這對美國毒素市場意味著市場增長將出現中等個位數下降，而美國填充劑市場將下降 10% 左右。就像我們說的那樣，隨著我們在今年上半年表現強勁，這些增長率將因季度而異。當然，如果出現嚴重衰退這樣的情況，失業率飆升，那不是我們考慮過的事情。或者另一方面，如果宏觀經濟環境穩定或改善，那將代表對我們的計劃有利。

Our next question is from Gary Nachman with BMO Capital Markets.

我們的下一個問題來自 BMO Capital Markets 的 Gary Nachman。

First question is on neuro in the quarter. It's actually weaker than we thought. So was there any additional pressure on gross-to-net, maybe for the oral CGRPs? And what sort of inflection are you expecting for Vraylar and MDD, how rapid do you think that adoption might be this year?

第一個問題是關於本季度的神經。它實際上比我們想像的要弱。那麼，是否有任何額外的壓力，可能是針對口服 CGRP？您預計 Vraylar 和 MDD 會出現什麼樣的變化，您認為今年採用的速度有多快？

And then, Rick, you recently said that you would be -- in an article that you would be lifting the self-imposed $2 billion annual cap on business development that you have more capacity to do deals. So how much capacity do you guys have what areas are you looking to be most aggressive? And how important is it to add sizable marketed products into the mix? Or would it be mostly focused on pipeline?

然後，里克，你最近在一篇文章中說，你將取消自己設定的每年 20 億美元的業務發展上限，你有更多的能力進行交易。那麼你們有多少能力，你們希望在哪些領域最具侵略性？將可觀的營銷產品添加到產品組合中有多重要？或者它會主要集中在管道上嗎？

Yes. I'll take the first one, it's Jeff. Thanks for the question. No, we did not see material incremental pressure on the gross-to-net. We did see a little softening versus our expectation on the overall preventative marketplace, but it was quite modest. So no, fairly consistent trending. I mean if you look at our new prescription capture and the oral market, it's basically a 50-50 shared capture rate between ourselves and the major competitor.

是的。我選第一個，他是傑夫。謝謝你的問題。不，我們沒有看到毛淨值的實質性增量壓力。與我們對整體預防市場的預期相比，我們確實看到了一些疲軟，但這是相當溫和的。所以不，相當一致的趨勢。我的意思是，如果你看看我們的新處方捕獲和口服市場，我們和主要競爭對手之間基本上有 50-50 的共享捕獲率。

In terms of the Vraylar adoption trend, we had discussed previously because we really have very, very strong access for Vraylar that we would anticipate a pretty rapid inflection in adoption for the depression indication, the adjunctive depression indication. As I mentioned in my remarks, that's what we've seen. So we're quite encouraged. I mean we can see a significant trend break on the new prescription adoption versus what was already a very nice growth rate for the Bipolar I indication.

就 Vraylar 採用趨勢而言，我們之前已經討論過，因為我們確實有非常非常強大的 Vraylar 訪問權限，我們預計抑鬱症適應症（輔助抑鬱症適應症）的採用率會出現相當快的變化。正如我在發言中提到的，這就是我們所看到的。所以我們很受鼓舞。我的意思是我們可以看到新處方採用的重大趨勢與 Bipolar I 適應症已經非常好的增長率相比。

So I think the early dynamics, and again, it's only really been a month here in January where our sales force has been out promoting the new indication. We're quite encouraged in terms of the market response, both from the metrics in terms of IQVIA, the scripts we see, but also the qualitative feedback from the customers.

所以我認為早期的動態，再一次，它只是在 1 月份的一個月，我們的銷售人員一直在推廣新的適應症。我們對市場反應感到非常鼓舞，無論是從 IQVIA 的指標、我們看到的腳本，還是來自客戶的定性反饋。

And on deal capacity, we obviously look at business development based on what we believe are -- we're trying to accomplish strategically in each of the therapeutic areas that we're operating in. we identify areas that we think would be good opportunities for us, and then we look to see if we can find those kinds of assets.

在交易能力方面，我們顯然是根據我們所相信的來看待業務發展——我們正在努力在我們經營的每個治療領域實現戰略性的目標。我們確定了我們認為是好的機會的領域我們，然後我們看看是否能找到這些類型的資產。

As I mentioned before, I think we're in the fortunate position that we can drive very strong growth. with the assets that we have on the market today as well as what's coming out of our pipeline over the next 3 or 4 years. That gives us the ability to be able to return to growth and then drive that high single-digit growth through the end of the decade. .

正如我之前提到的，我認為我們處於幸運的位置，我們可以推動非常強勁的增長。我們今天在市場上擁有的資產以及未來 3 或 4 年內即將推出的產品。這使我們能夠恢復增長，然後在本世紀末推動高個位數增長。 .

And we're also fortunate that after HUMIRA, we have a -- relative to our peers, we have a very low LOE exposure. So we don't have a lot of downward pressure on the business. Now having said that, we've done an excellent job of paying down the incremental debt from the Allergan transaction, we put that $2 billion cap in place when we did the Allergan acquisition that allowed us to focus again on some earlier-stage assets. And I'd remind everyone that was about 4x what our historical practice has been for those kinds of assets. So there was plenty of capacity to do that.

我們也很幸運，在 HUMIRA 之後，我們有一個 - 相對於我們的同行，我們的 LOE 風險非常低。所以我們對業務沒有太大的下行壓力。話雖如此，我們在償還艾爾建交易中增加的債務方面做得非常出色，我們在收購艾爾建時設定了 20 億美元的上限，這使我們能夠再次專注於一些早期資產。我要提醒大家，這大約是我們歷史上對這類資產的做法的 4 倍。所以有足夠的能力來做到這一點。

But we're certainly in a position now that if the right thing were to come along, we could do a transaction that would be much larger. We certainly have the financial wherewithal to be able to do that. And we've certainly shown that we were able to do that and create value in the assets that we bring in. The areas that we typically look at are aligned with our therapeutic growth areas. So immunology, oncology, certain areas of neuroscience and eye care, I would say, are the predominant areas as well as aesthetics. We obviously continue to look for opportunities in the states. They tend to be smaller acquisitions, though.

但我們現在肯定處於這樣的位置，如果出現正確的事情，我們可以進行規模更大的交易。我們當然有能力做到這一點。我們當然已經表明我們能夠做到這一點並在我們帶來的資產中創造價值。我們通常關注的領域與我們的治療增長領域保持一致。因此，免疫學、腫瘤學、神經科學和眼保健的某些領域，我想說，是主要領域以及美學。我們顯然繼續在各州尋找機會。不過，它們往往是規模較小的收購。

And so at the end of the day, I feel good about where we are, and we've been quite active. We have a very active business development group. And we'll continue to look at those. And like I said, if we find something that's of interest, and it could really help us round out a category that we're in, then you should expect us to act on that.

所以在一天結束的時候，我對我們所處的位置感覺很好，而且我們一直非常活躍。我們有一個非常活躍的業務開發團隊。我們將繼續研究這些。就像我說的，如果我們發現了一些有趣的東西，並且它確實可以幫助我們完善我們所在的類別，那麼您應該期望我們對此採取行動。

It comes from Carter Gould with Barclays.

它來自巴克萊銀行的卡特古爾德。

Maybe to come back to aesthetics. It does sound like you built in conservatism on a number of fronts. I wanted to also -- you didn't touch much around sort of China reopening and how you expect that sort of business to -- as it comes back, if you expect it to sort of return to how it was? Or if that will evolve differently.

也許回到美學。聽起來您確實在許多方面建立了保守主義。我還想——你並沒有過多地談到中國的重新開放，以及你對這種業務的期望——當它回來時，你是否希望它恢復到原來的樣子？或者如果那會以不同的方式發展。

And then in the -- I guess as we think then around the guidance for '23 and the link you've drawn to '24 as you sort of maybe if the guidance potentially evolves over '23, should we think about that link remaining intact? Or is that sort of a near-term phenomenon and that will sort of, I guess, disappear going forward.

然後在 - 我想當我們圍繞 23 年的指南和你繪製到 24 年的鏈接進行思考時，如果指南可能在 23 年之後發生變化，我們是否應該考慮保持完整的鏈接？或者這是一種近期現象，我猜它會在未來消失。

Carrie, why don't you touch on the aesthetics question.

嘉莉，你為什麼不談談美學問題。

Yes. So your question around China, and I'd say China is our second largest global business. It has demonstrated significant growth in the past few years and proven to be very responsive to the increased promotion that we're putting into that market. Of course, in 2022, China COVID-related issues did impact the aesthetics market, especially in the second and fourth quarters. .

是的。所以你的問題是關於中國的，我想說中國是我們第二大全球業務。它在過去幾年中表現出顯著的增長，並證明對我們在該市場投入的更多促銷活動非常敏感。當然，2022 年，中國 COVID 相關問題確實影響了美容市場，尤其是在第二和第四季度。 .

Now as we look at the year beginning in China and as everyone is returning from the Chinese New Year, it does look like the current wave has peaked. And that the situation is beginning to improve and will continue to improve through the first half of 2023, and we're expecting a full recovery in the market in Q3 and for the second half the year. So despite the challenges in 2022, China still posted positive growth, and we will definitely be continuing our investments in China in 2023 and beyond.

現在，當我們回顧中國的新年伊始，隨著每個人都從農曆新年歸來，目前的浪潮確實已經見頂。而且情況開始好轉，並將在 2023 年上半年繼續改善，我們預計第三季度和下半年市場將全面復甦。因此，儘管 2022 年面臨挑戰，但中國仍實現了正增長，我們肯定會在 2023 年及以後繼續在中國投資。

And Carter, this is Rob. I'll try to answer your second question. I think the way to think about '24 -- clearly, as we go through the year, we always look at the trends and contemplate what that could mean for flow through in '24. But the reason we gave you that guidance range, we mentioned the $10.70 being -- the way to think about it as a floor for '24 is because of the dynamics around the HUMIRA erosion.

卡特，這是羅伯。我會嘗試回答你的第二個問題。我認為思考 24 年的方式——很明顯，在我們度過這一年的過程中，我們總是關注趨勢並思考這對 24 年的流動意味著什麼。但是我們給你這個指導範圍的原因，我們提到了 10.70 美元——將其視為 24 年底部的方式是因為 HUMIRA 侵蝕的動態。

So if we do better in '23 and more of it happens in '24, then you can at least anchor back to we're not going to fall below that $10.70 EPS floor in our guidance range. So we always would factor in trends, but that's the way to think about it. If it's just the erosion on HUMIRA is better this year than we have in this guidance. We want to make sure you understood that what it means potentially for '24. So that's again, always factor in trends. But as we sit here today, that's the best way to think about it.

因此，如果我們在 23 年做得更好，而更多的情況發生在 24 年，那麼你至少可以確定我們不會跌破我們指導範圍內的 10.70 美元 EPS 下限。所以我們總是會考慮趨勢，但這就是思考它的方式。如果只是今年 HUMIRA 的侵蝕比我們在本指南中的要好。我們想確保您了解它對 24 世紀的潛在意義。所以這又是，始終考慮趨勢。但當我們今天坐在這裡時，這是思考它的最佳方式。

Maybe just let me add one thing that might help clarify it. I think you should think about HUMIRA in '24. We believe we're going to get to a certain level of price and volume in '24, almost regardless of what happens in '23 because of the competitive dynamic. And so when we talk about the shift, what we're really talking about is inflating '23. If you anchor '24 is a solid point that we have a high level of confidence of where HUMIRA's tail will be in '24. And the only thing that happens to shift it between '23 and '24 is that we do much better in '23 than we expected, right? So that inflates but it still anchors against the '24 point. That's the way to think about this.

也許讓我添加一件事可能有助於澄清它。我認為你應該考慮 24 年的 HUMIRA。我們相信我們將在 24 年達到一定的價格和數量水平，幾乎不管 23 年由於競爭動態而發生什麼。因此，當我們談論這種轉變時，我們真正談論的是 23 年的膨脹。如果你錨定 '24 是一個堅實的點，我們對 HUMIRA 的尾巴將在 '24 中的位置有很高的信心。唯一使它在 23 年和 24 年之間發生變化的是我們在 23 年的表現比我們預期的要好得多，對吧？所以它膨脹了，但它仍然錨定在 24 點上。這就是思考這個問題的方式。

It comes from Steve Scala with Cowen.

它來自 Steve Scala 和 Cowen。

The low end of 2023 guidance implies 22% EPS erosion, the high end of Q1 guidance assumes 21% EPS erosion. How is it possible that Q1 could be in line with the full year and not appreciably better? It seems as though the Q1 guide is low? Or is that because AbbVie believes the floor on HUMIRA price is already reached? Maybe another way to restate the question. What should be our anticipation for the quarterly cadence of EPS as we go through the year?

2023 年指引的低端意味著 EPS 侵蝕 22%，第一季度指引的高端假設 EPS 侵蝕 21%。 Q1 怎麼可能與全年持平而不明顯好轉？好像Q1指南低？或者是因為 AbbVie 認為 HUMIRA 的底價已經達到？也許另一種方式來重申這個問題。我們對全年 EPS 季度節奏的預期應該是什麼？

So Steve, so I think the best way is one anchor on the guidance we gave you on U.S. HUMIRA today. So we said -- for the first quarter, we said it would be 27% erosion. And so -- and that's going to -- the vast majority of that will be priced. And we said because there'll be nine biosimilars coming to market in the middle of the year, we would expect more of the erosion to come in the second half of the year. So you have to factor that dynamic into the way you look at the quarters that there'll be more erosion in the second half of the year for HUMIRA versus the first half of the year.

所以史蒂夫，所以我認為最好的方法是我們今天給你的關於美國 HUMIRA 的指導。所以我們說 - 對於第一季度，我們說這將是 27% 的侵蝕。因此——這將是——其中絕大多數將被定價。我們說，因為今年年中將有九種生物仿製藥上市，我們預計下半年會出現更多的侵蝕。因此，你必須將這種動態因素納入你看待季度的方式，即 HUMIRA 與上半年相比，今年下半年的侵蝕會更多。

Then you also have to factor in that you've got things like aesthetics, where we haven't quite lapped the economic impact yet, right? So in the first quarter, you have a dynamic where you will see aesthetics still down, right? But when we get into the middle of the year, when we lap it, that also affects your year-over-year growth rates. And then the underlying performance of the growth platform as we continue to drive those brands, you'll see those growth rates accelerate.

然後你還必須考慮到你有美學之類的東西，我們還沒有完全了解經濟影響，對吧？所以在第一季度，你會看到審美仍然低迷，對吧？但是當我們進入年中時，當我們完成它時，這也會影響你的同比增長率。然後，隨著我們繼續推動這些品牌，增長平台的潛在表現，你會看到這些增長率加速。

So those are all the things that would factor in as you look at the quarterly -- really, we've given you Q1 and then full year. We haven't given you Q2, 3 and 4. But that -- those are the variables I would look at. There's not really a whole lot in terms of if you look at investment, for example, that you have to flex. We do tend to see some higher levels typically in the fourth quarter. So you could -- you could look at historically our investment patterns and use that as a proxy. But those are the variables to consider as you think about the first quarter versus the rest of the year.

所以這些都是你看季度時會考慮的因素——真的，我們給了你第一季度，然後是全年。我們還沒有給你 Q2、3 和 4。但是那是我要考慮的變量。就投資而言，實際上並沒有很多，例如，你必須靈活。我們確實傾向於在第四季度看到一些更高的水平。所以你可以 - 你可以從歷史上看我們的投資模式並將其用作代理。但這些是您在考慮第一季度與今年剩餘時間時要考慮的變量。

It will come from Tim Anderson with Wolfe Research.

它將來自 Wolfe Research 的 Tim Anderson。

I'm going to torch you with a couple more questions on the same subject as others. The U.S. HUMIRA erosion guidance of minus 37% in '23. How much of that is price versus volume? If I look at what your Q1 U.S. HUMIRA erosion is, so the guidance is minus 27%. Given that volumes for HUMIRA are, call it, 5% positive, that would suggest the price cuts may be in the 30% to 35% range. So can we triangulate off of the Q1 guidance to understand what percent of that minus 37% comes from price?

關於與其他人相同的主題，我將向您提出更多問題。 23 年美國 HUMIRA 侵蝕指導值為負 37%。其中有多少是價格與數量的比值？如果我看看你的第一季度美國 HUMIRA 侵蝕是多少，那麼指導是負 27%。鑑於 HUMIRA 的銷量為 5%，這表明降價幅度可能在 30% 至 35% 之間。那麼我們能否根據第一季度的指導進行三角測量，以了解負 37% 中有多少百分比來自價格？

And then the second question, again, goes back to 2024. I know there's lots of uncertainty on the exact rate of erosion for HUMIRA in '23. But if you hit that minus 37% right on the nose, would 2024 erosion likely be slower or faster than net minus 37%.

然後第二個問題再次回到 2024 年。我知道 HUMIRA 在 23 年的確切侵蝕率存在很多不確定性。但是，如果你恰好碰到負 37%，那麼 2024 年的侵蝕可能會比淨負 37% 更慢或更快。

So Tim, on your question related to price and volume. The way to think about it is in the first half of the year, the 27% in the first quarter, is the vast majority of that is price, right? So there is some volume impact, but not very much. It's in the second half -- what you'll see is in the second half, the overall erosion will step up and think of it as equivalent between price and volume because you're going to have -- we know we'll have rebate rates in some cases, increasing as well as the nine biosimilars coming to market, we expect to see more volume erosion.

那麼蒂姆，關於你的問題與價格和數量有關。想一想是上半年，一季度的27%，絕大部分是價格吧？所以有一些體積影響，但不是很大。這是在下半年——你會在下半年看到，整體侵蝕將加劇，並將其視為價格和數量之間的等價物，因為你將擁有——我們知道我們會有回扣在某些情況下，隨著 9 種生物仿製藥進入市場而增加，我們預計會看到更多的銷量下降。

So as you think about -- as you're trying to triangulate the price volume with the guidance you've given, 27% vast majority's price, second half of the year, you'll have some more volume kicking in. That's I think the best way to think about the price volume split. And then your question on '24, is your question in terms of the percentage or the absolute?

因此，當你考慮時——當你試圖根據你給出的指導對價格量進行三角測量時，27% 的絕大多數價格，今年下半年，你會有更多的成交量。這就是我的想法考慮價量分割的最佳方式。然後你關於 24 年的問題是百分比還是絕對值？

Percentage. So if you hit the minus 37% this year, which is your guidance for U.S. HUMIRA, will the rate of erosion in '24 be greater or less than that 37%?

百分比。因此，如果你今年達到負 37%，這是你對美國 HUMIRA 的指導，那麼 24 年的侵蝕率會大於還是小於 37%？

So we're not going to give you a 2024 guidance, Tim. I think the way to think about '24 is we would expect to see additional price but albeit not at the same level as '23 and more volume coming through because you're going to have up to 10 biosimilars in the market for the full year. So we would expect to see more of a volume impact in '24 that we would expect to see in '23.

所以我們不會給你 2024 年的指導，蒂姆。我認為考慮 24 年的方式是我們預計會看到額外的價格，但不會與 23 年處於同一水平，而且會有更多的銷量，因為全年市場上將有多達 10 種生物仿製藥.因此，我們希望在 24 年看到更多我們希望在 23 年看到的數量影響。

It comes from Chris Shibutani with Goldman Sachs.

它來自 Chris Shibutani 和 Goldman Sachs。

You previously commented about the operating margin trajectory of '23 into '24. I believe characterizing them is basically flattish. Is that still the case? And then across the immunology category broadly, we're seeing some -- a lot of cross-currency mix dynamics, clearly, with your portfolio being part of that.

您之前曾評論過 23 年到 24 年的營業利潤率軌跡。我認為描述它們基本上是平淡的。現在還是這樣嗎？然後在廣泛的免疫學類別中，我們看到了一些——很多跨貨幣組合動態，很明顯，你的投資組合就是其中的一部分。

What is your expectation about the potential for some of the newer mechanisms that are emerging with clinical data. Are you keen to figure out whether you want to invoke those as part of your portfolio? What do you see the outlook for novel mechanisms, given that we're going to have some biosimilars to some of the most standard-of-care approaches PNSIL-23.

您對隨著臨床數據出現的一些新機制的潛力有何期望？您是否想弄清楚是否要將它們作為您投資組合的一部分？考慮到我們將為一些最標準的護理方法 PNSIL-23 提供一些生物仿製藥，您如何看待新機制的前景。

Chris, this is Rob. I'll take your first question. I think for modeling purposes, I would expect operating margins stay roughly at this level in '24 and then begin expanding again in '25 with our return to robust sales growth. I think the pace of that expansion will depend on investment needs as we will always prioritize R&D and SG&A investment to drive long-term growth, but that's the best way to think through '24 and then what the operating margin will look like in '25 and beyond.

克里斯，這是羅伯。我會回答你的第一個問題。我認為出於建模目的，我預計營業利潤率在 24 年大致保持在這個水平，然後隨著我們恢復強勁的銷售增長而在 25 年再次開始擴大。我認為擴張的速度將取決於投資需求，因為我們將始終優先考慮研發和 SG&A 投資以推動長期增長，但這是思考 24 年以及 25 年營業利潤率的最佳方式超越。

And Chris, it's Jeff. I'll maybe kick off on your immunology question and then ask Tom to comment on some dynamics as well. So it is very, very clear that certainly in the midterm, the most excitement across these immunology categories are for SKYRIZI and RINVOQ. It's quite striking. And I think Tom mentioned there's still incredible interest in a next wave of dermatologic indications that follow on for atopic dermatitis that he highlighted.

克里斯，是傑夫。我可能會開始你的免疫學問題，然後請湯姆也對一些動態發表評論。所以非常非常清楚，在中期，這些免疫學類別中最令人興奮的是 SKYRIZI 和 RINVOQ。這是相當驚人的。我認為 Tom 提到，對於他強調的特應性皮炎，下一波皮膚病學適應症仍然令人難以置信。

And really, as I noted in my remarks, I mean, the amount of excitement around the IL-23 and particularly our IL-23 across these indications is really profound. Now having said that, we are watching the competitive landscape for some -- maybe potentially some novel orals. We don't see them as major players. As we look deeper in the pipeline, we can see that there is the possibility for combination use of novel biologics or biomarker-driven approaches, particularly in IBD. And we monitor those very carefully as we look at our long-range plan. And Tom, I don't know if you want to address some of the things that are back in our pipeline in terms of immunology.

實際上，正如我在評論中指出的那樣，我的意思是，圍繞 IL-23，尤其是我們的 IL-23 在這些適應症中的興奮程度非常深遠。話雖如此，我們正在觀察一些競爭格局——可能是一些新穎的口頭表達。我們不認為他們是主要參與者。當我們深入研究管道時，我們可以看到結合使用新型生物製劑或生物標誌物驅動方法的可能性，特別是在 IBD 中。我們在審視我們的長期計劃時非常仔細地監控這些。湯姆，我不知道你是否想解決我們在免疫學方面的一些問題。

Sure. I mean I think the -- I just want to start saying that with SKYRIZI and RINVOQ really raised the bar in terms of efficacy and you see it in mucosal healing, for example. So the bar is getting higher and we will continue to do that. But even to show that we're raising the bar, we're also going to do -- we're going to read out head-to-head studies this year with STELARA and Otezla. So another way to kind of show that what we have is really very profound in terms of responses we're seeing with patients.

當然。我的意思是，我認為——我只想開始說，SKYRIZI 和 RINVOQ 確實提高了療效標準，例如，你可以在粘膜癒合中看到它。所以門檻越來越高，我們將繼續這樣做。但即使是為了表明我們正在提高標準，我們也將要做——我們將在今年與 STELARA 和 Otezla 進行面對面的研究。因此，另一種方式表明，就我們在患者身上看到的反應而言，我們所擁有的確實非常深刻。

And we continue -- I mean, honestly, we look at the field. We look at competitors. We're hearing data of S1P1 inhibitors, but the data appears to be less effective based on a number of patients which are discontinuing treatment and the signals that we see cardiovascular and others that are similar to what we've seen with previous ones. So I mean, again, without having seen the data, it's all difficult to kind of predict how they'll be able to do, except that our data with RINVOQ and SKYRIZI are very strong, durable and again, very strong at the level of endoscopy also.

我們繼續 - 我的意思是，老實說，我們看看這個領域。我們看看競爭對手。我們正在聽取 S1P1 抑製劑的數據，但根據一些正在停止治療的患者以及我們看到的心血管信號和其他與我們之前看到的信號相似的信號，這些數據似乎不太有效。所以我的意思是，再一次，在沒有看到數據的情況下，很難預測他們將如何做，除了我們與 RINVOQ 和 SKYRIZI 的數據非常強大、持久，而且在內窺鏡也。

So we think we have already a competitive edge. We continue we'll see PMR data later this year. We have talked about our RIPK1 inhibitor, again for mucosal healing that's in the clinic right now. We're looking at additional indications. So over time, obviously, we're going to look at additional mechanisms. But not necessarily just pushing down on the same cytokines as JAKs, but looking at other target pathways of things that happen in the skin or in GI, again, mucosal healing being an [antagonal] pathway. And this is where we think a combination of our immunomodulators like RINVOQ and SKYRIZI with other mechanisms will combine well to give even more profound responses.

所以我們認為我們已經擁有了競爭優勢。我們將在今年晚些時候看到 PMR 數據。我們已經談到了我們的 RIPK1 抑製劑，它也是目前在臨床上用於粘膜癒合的抑製劑。我們正在研究其他跡象。所以隨著時間的推移，很明顯，我們將研究其他機制。但不一定只是壓低與 JAKs 相同的細胞因子，而是觀察皮膚或 GI 中發生的事情的其他目標途徑，同樣，粘膜癒合是一種 [拮抗] 途徑。這就是我們認為我們的免疫調節劑（如 RINVOQ 和 SKYRIZI）與其他機制的組合將很好地結合起來產生更深刻的反應的地方。

It comes from Colin Bristow with UBS.

它來自 Colin Bristow 和 UBS。

For all the helpful color so far. So maybe a broader question just with regards to HUMIRA biosimilars. I'm just curious like, what is the broader impact you anticipate on the I&I market just in terms of net price has been sort of a question we've been getting a lot of people are trying to wrap their heads around -- and then maybe just one on your CF triplet. I know that the trial is ongoing. Can you give us an update here? How is the progress? Should we still expect data later this year?

到目前為止所有有用的顏色。因此，也許只是關於 HUMIRA 生物仿製藥的更廣泛的問題。我只是好奇，就淨價而言，您對 I&I 市場的更廣泛影響是什麼？我們一直在問這個問題，很多人都在努力思考——然後也許只有一個在你的 CF 三聯體上。我知道審判正在進行中。你能在這裡給我們更新嗎？進展如何？我們還應該期待今年晚些時候的數據嗎？

Yes, I'll take the one on the immunology marketplace. I think that the impact overall in the category for net price would be modest. And I think a lot of it has to do what Tom and I've discussed before, which is the -- just the pure profile of some of these agents particularly SKYRIZI and RINVOQ and either others in the pipeline that are coming. I mean they really are setting different standards of care versus what they've seen in the past. And certainly, the physicians and the payers are recognizing this.

是的，我會選擇免疫學市場上的那個。我認為該類別對淨價的總體影響不大。而且我認為其中很多必須做湯姆和我之前討論過的事情，這就是 - 只是其中一些代理人的純粹概況，特別是 SKYRIZI 和 RINVOQ 以及即將到來的管道中的任何其他人。我的意思是，他們確實設定了與過去所見不同的護理標準。當然，醫生和付款人都認識到了這一點。

I'll give a really quick example on one of our major products, which is RINVOQ. I mean RINVOQ, based on the label changes that have taken place is already a post-TNF type of dynamic. And so the pricing is going to be the pricing there's no incremental ability to step it, for example. The other thing I would note is on SKYRIZI, we have four head-to-head trials against all the major competitors and another one coming with Otezla, as Tom noted.

我將就我們的主要產品之一 RINVOQ 給出一個非常簡單的示例。我的意思是 RINVOQ，基於已經發生的標籤變化，已經是後 TNF 類型的動態。因此，定價將是定價，例如，沒有增量能力來加強它。我要注意的另一件事是在 SKYRIZI 上，正如湯姆指出的那樣，我們與所有主要競爭對手進行了四次面對面的試驗，另一次與 Otezla 進行了試驗。

So you start to see that level of performance, whether it's against STELARA, multiple TNFs. Otezla, as I said, that's pending here. And it just becomes very clear that you're just going to achieve much higher levels of clearance and relief. So we feel pretty confident that the pricing impact over time, particularly in the U.S. market will be very modest. And certainly, we can navigate that based on the power of the performance of the portfolio.

所以你開始看到這種性能水平，無論是針對 STELARA 還是多種 TNF。正如我所說，Otezla 在這裡待定。很明顯，您將獲得更高水平的清除和緩解。因此，我們非常有信心，隨著時間的推移，定價影響將非常小，尤其是在美國市場。當然，我們可以根據投資組合的性能來進行導航。

This is Tom. I'll just answer about the cystic fibrosis program. Again, this program continues. And just to remind you, we're working on a triplet and where we believe that two of the three components of -- for this drug, this triplet, we have best-in-class assets. But we were looking for another part of the triplet called the C2 corrector, where last year, the previous ones basically didn't give the meaningful improvement we were expecting in FEV1 sweat chloride.

這是湯姆。我只會回答有關囊性纖維化計劃的問題。再次，這個程序繼續。只是提醒你，我們正在研究三聯體，我們相信三個組成部分中的兩個 - 對於這種藥物，這個三聯體，我們擁有一流的資產。但我們一直在尋找三元組的另一部分，稱為 C2 校正器，去年，以前的那些基本上沒有給出我們預期的 FEV1 汗液氯化物的有意義的改進。

So we've actually, in our discovery groups, continue to develop new ones. In the last year, we've moved our ABBV-576 forward. in SAB in Phase I studies. We continue to see these, again, safety, high exposures, good PK, things that with -- if you combine with our preclinical data, makes us think it will, it has a potential to be best-in-class -- and that triplet again with -- is -- first of all, to being tested, we'll have data this year to actually show how they behave together. And later at this part of this year, I'll be able to give an update.

所以我們實際上在我們的發現小組中繼續開發新的。去年，我們向前推進了 ABBV-576。在 SAB I 期研究中。我們繼續看到這些，再次，安全性，高暴露，良好的 PK，與 - 如果你結合我們的臨床前數據，讓我們認為它會，它有可能成為一流的 - 而且那再次三重奏——是——首先，要接受測試，我們今年將有數據來實際展示他們在一起的表現。在今年的這個時候，我將能夠提供更新。

Our next question is from Trung Huynh with Credit Suisse.

我們的下一個問題來自瑞士信貸的 Trung Huynh。

Trung Huynh from Credit Suisse. Two, if I may. So I was just wondering on your thoughts more broadly on the pricing dynamics in the EU and U.S. So in the EU, you recently exited the U.K. pricing agreement. In Europe, it does feel like there's -- it's just becoming an increasingly complicated pricing environment. There are a number of reforms being proposed in Europe. So I guess my first question is do you see these changes being material or any headwinds to you in your growth ex U.S.?

瑞士信貸的 Trung Huynh。兩個，如果可以的話。所以我只是想知道你對歐盟和美國定價動態的更廣泛的想法所以在歐盟，你最近退出了英國定價協議。在歐洲，感覺確實存在——它正變得越來越複雜的定價環境。歐洲提出了許多改革方案。所以我想我的第一個問題是，您是否認為這些變化對您在美國以外的增長有重大影響或不利因素？

And then secondly, can you just perhaps talk about your reasons you decided not to renew your membership for pharma and bio? How are you going to remain engaged in D.C. and have a voice when it comes to things like IRA and pricing controls.

其次，您能否談談您決定不續籤制藥和生物會員資格的原因？當涉及 IRA 和定價控制等問題時，您將如何繼續參與 D.C. 並發表意見。

Yes. Thanks for the question. I'll take the first one there in terms of the EU. We do see some movement there, particularly in the, let's say, industry tax, and I'll comment on the so-called VPAS in the U.K. In some ways, whether or not we were in that voluntary program or outside of the voluntary program, the impact is about the same. And frankly, it was a policy decision because we really think that the U.K. government needs to reform that VPAS. They didn't plan properly for how things might dynamically evolve in the U.K., and it's a very substantial part of the revenue now that is causing problems, I think, across all of the company.

是的。謝謝你的問題。就歐盟而言，我將採取第一個。我們確實在那裡看到了一些變化，尤其是在行業稅方面，我將對英國所謂的 VPAS 進行評論。在某些方面，無論我們是否在該自願計劃中或在自願計劃之外，效果差不多。坦率地說，這是一項政策決定，因為我們真的認為英國政府需要改革 VPAS。他們沒有為英國的動態發展制定適當的計劃，我認為，現在收入的很大一部分正在引起整個公司的問題。

So it was a position of -- policy position, net neutral. It didn't matter, frankly, whether we were in or not and the U.K. is a relatively modest business for us. We are seeing perhaps more importantly, some changes in the German law, as you're probably aware of. And that is, I think, a modest net pressure that will come in Europe in Germany, in particular, because there's the move, as you may know, from 1 year of free pricing to 6 months. There's a modest increase in rebates, for example. So we do see some austerity impact. But on the bigger scheme, it's -- I wouldn't say it's material to our growth platform that we've been discussing.

所以這是一個立場——政策立場，網絡中立。坦率地說，我們是否在英國並不重要，英國對我們來說是一個相對溫和的行業。或許更重要的是，我們看到德國法律發生了一些變化，您可能已經知道了。那就是，我認為，歐洲在德國將面臨適度的淨壓力，特別是因為正如您所知，從 1 年的免費定價到 6 個月的轉變。例如，回扣略有增加。所以我們確實看到了一些緊縮政策的影響。但在更大的計劃中，我不會說這對我們一直在討論的增長平台很重要。

And Trung, this is Rob. In terms of international prices, I mean, typically, we see year-over-year decline of low to mid-single digits, and that's the way we're modeling it for '23 as well.

Trung，這是 Rob。就國際價格而言，我的意思是，通常情況下，我們會看到中低個位數的同比下降，這也是我們為 23 年建模的方式。

And then on pharma, this is Rick. Obviously, every year, we evaluate any kind of significant investment that we're going to make. And we make a decision as to whether or not we believe that investment is appropriate and is going to have the right level of return at that point in time. And ultimately, we made the decision around pharma based on that.

然後在製藥方面，這是瑞克。顯然，每年我們都會評估我們將要進行的任何類型的重大投資。我們會決定我們是否認為投資是合適的，並且會在那個時間點獲得適當的回報水平。最終，我們基於此做出了關於製藥的決定。

We have a very significant government affairs group that's been active and been in place ever since we came into existence back in 2013, we've grown that organization. We did grow it somewhat this year as well in anticipation of not being part of pharma. We plan on being active as we have been in the past to try to appropriately advocate for things that we think are appropriate for patients. And I think that group is quite capable of being able to do that.

我們有一個非常重要的政府事務小組，自從我們在 2013 年成立以來就一直很活躍，我們已經發展了這個組織。今年我們確實有所增長，因為我們預計不會成為製藥公司的一部分。我們計劃像過去一樣積極主動地嘗試適當地倡導我們認為適合患者的事情。我認為該小組完全有能力做到這一點。

And I would tell you that at a point in the future, we might decide to go back into pharma. But at this point, we've made the decision that we think that investment could be used elsewhere to be more effective. It's as simple as that.

我會告訴你，在未來的某個時刻，我們可能會決定重新回到製藥業。但在這一點上，我們已經做出決定，我們認為可以將投資用於其他地方以提高效率。就這麼簡單。

Our next question is from Geoff Meacham with Bank of America.

我們的下一個問題來自美國銀行的 Geoff Meacham。

I appreciate all the perspective on guidance. I just had a follow-up on it. Rick, on your comments on the HUMIRA scale for starting next year in the U.S. I think when you look at other geographies, international revenues, you're still seeing double-digit declines after 4 years or so. Maybe just give us some context for what you're seeing there broadly versus what we could expect for the U.S. And just to be clear, when you see next year the impact from all the HUMIRA biosimilars, how much do you think that biosimilar STELARA may play a role here when you look at your assumptions for HUMIRA erosion?

我感謝所有關於指導的觀點。我剛剛對它進行了跟進。里克，關於你對明年在美國開始的 HUMIRA 規模的評論。我認為當你看看其他地區的國際收入時，你仍然會在 4 年左右後看到兩位數的下降。也許只是給我們一些關於你在那裡廣泛看到的情況與我們對美國的預期的背景。而且要明確一點，當你明年看到所有 HUMIRA 生物仿製藥的影響時，你認為生物仿製藥 STELARA 可能有多大當您查看您對 HUMIRA 侵蝕的假設時，您是否在此處發揮了作用？

And then second question, just on the BD front, you guys talked about some of the therapeutic categories that you're interested in. But with the appetite to expand into -- expand the menu here and to say more orphan indications, I think across the landscape, some companies in the I&I space are getting into more niche indication. I wasn't sure if that was something that you guys would consider?

然後是第二個問題，就 BD 方面而言，你們談到了一些您感興趣的治療類別。但隨著胃口擴大到 - 擴大這裡的菜單並說出更多孤兒適應症，我認為在景觀方面，I&I 領域的一些公司正在進入更多利基適應症。我不確定這是否是你們會考慮的事情？

So I think on the HUMIRA tail, just to maybe clarify what I said is I would expect that as we move through 2024 then in 2025 and 2026, we would start to see a more stable tail for HUMIRA. In other words, we're going to see erosion in 2024. I want to make sure I didn't somehow communicate that, that wasn't the case.

所以我認為在 HUMIRA 的尾巴上，為了澄清我所說的，我預計隨著我們在 2024 年，然後在 2025 年和 2026 年，我們將開始看到 HUMIRA 的尾巴更穩定。換句話說，我們將在 2024 年看到侵蝕。我想確保我沒有以某種方式傳達這一點，事實並非如此。

So if you look at OUS, I think what's probably deceiving to you is you had different countries going biosimilar at different periods in time. So you can't necessarily look at that as an analog because it's so heterogeneous in the year that those countries went biosimilars. So you are correct. Yes, it is still experiencing double-digit decline, but it's been driven by the fact that those countries have not -- some of those countries haven't reached stability yet. But typically -- and the U.S. market is a little different because you have all a large number -- you have a small number of large payers who drive the bulk of the activity in this market.

所以如果你看看 OUS，我認為你可能會被不同的國家在不同的時間段進行生物仿製藥。所以你不一定要把它看作一個類比，因為它在那些國家採用生物仿製藥的那一年是如此的異質化。所以你是對的。是的，它仍在經歷兩位數的下降，但這是因為這些國家還沒有——其中一些國家還沒有達到穩定。但通常情況下——美國市場有點不同，因為你有很多——你有少數大支付者推動了這個市場的大部分活動。

So it's more like some of the countries that did other kinds of government-wide activity, like in Germany as an example. And there, we do see after a couple of years, we've seen stability. So I think what's misleading you is you're looking at the overall number, but you're not factoring into that, the fact that these countries went biosimilar across a number of years.

所以它更像是一些在政府範圍內開展其他類型活動的國家，例如德國。在那裡，我們確實看到幾年後，我們看到了穩定性。所以我認為誤導你的是你在看總體數字，但你沒有考慮到這些國家多年來一直在進行生物仿製藥的事實。

Geoff, this is Rob. Just to add to that. So if you just look at this year, so about half of the erosion is going to come from newer markets like Puerto Rico, Canada and Mexico. So that, as Rick mentioned, we have different waves. And so you're still seeing some of those waves come through. You also have some volume going to new agents like SKYRIZI and RINVOQ, right? So that's something to keep in mind that that's a dynamic that's also playing out for HUMIRA in those markets.

傑夫，這是羅伯。只是為了補充這一點。所以如果你只看今年，那麼大約一半的侵蝕將來自波多黎各、加拿大和墨西哥等新興市場。因此，正如 Rick 提到的，我們有不同的波浪。所以你仍然會看到其中一些波浪通過。你們也有一些量給了像 SKYRIZI 和 RINVOQ 這樣的新代理商，對吧？因此，需要記住的是，在這些市場中，這種動態也在為 HUMIRA 發揮作用。

And then you typically see negative price trends in international markets, again, low to mid-single digits. So you're going to see some level of pressure there. So those are all factoring into the year-over-year on international HUMIRA something to make sure you're keeping in mind.

然後你通常會在國際市場上看到負價格趨勢，同樣是低至中個位數。所以你會在那裡看到一定程度的壓力。因此，這些都是國際 HUMIRA 同比增長的因素，以確保您牢記這一點。

And if you look at the STELARA dynamic with the biosimilar, I think there's a couple of dynamics that we're watching. And it does go back to my prior comments over the clinical differentiation. The first is that there will be less biosimilar competitive intensity against STELARA. Certainly, we've not seen anything like the nine that we were -- 9 or 10 that we're going to see on HUMIRA. And so -- and that price point is quite high actually. If you look at where STELARA is now with the branded program. Now I think maybe more importantly, as we've highlighted before, we've anticipated that entry.

如果你看看 STELARA 與生物仿製藥的動態，我認為我們正在觀察一些動態。這確實可以追溯到我之前對臨床分化的評論。首先是與 STELARA 的生物類似藥競爭強度將降低。當然，我們還沒有看到像我們將要在 HUMIRA 上看到的九個或十個這樣的東西。所以——這個價位實際上相當高。如果您通過品牌計劃查看 STELARA 現在的位置。現在我認為也許更重要的是，正如我們之前強調的那樣，我們已經預料到了該條目。

And certainly, in Crohn's, we have an ongoing head-to-head trial against STELARA that will read out towards the end of the year. We plan on putting that into promotion if and we believe it will be positive, particularly what we're studying, which is that endoscopic endpoint, which is really becoming the standard in the gastroenterology space. So we think we can parry quite well with the ultimate arrival of that IL -- the 12/23 versus our pure 23. So I hope that helps.

當然，在克羅恩病中，我們正在進行針對 STELARA 的頭對頭試驗，該試驗將在年底宣讀。如果我們相信它會是積極的，我們計劃將其推廣，特別是我們正在研究的內容，即內窺鏡終點，它真正成為胃腸病學領域的標準。所以我們認為我們可以很好地應對 IL 的最終到來——12/23 與我們的純 23。所以我希望這會有所幫助。

I think on your third question, again, what tends to drive our BD strategy is the long-term strategic road map that we put in place across the branch. So if you think about it, you mentioned immunology as an example. I would say in immunology, we have two fundamental objectives that we're trying to drive. There are still areas within immunology, where we believe we can significantly raise the effectiveness of the therapies that are used on patients to drive higher levels of remission or higher levels of endoscopic healing. In other words, better clinical outcomes within the areas that we're in. And so we have a tremendous amount of effort in those areas to bring next-generation assets, or as Tom mentioned in his comments, there are opportunities to potentially combine two mechanisms together to achieve that level of therapeutic benefit.

我認為關於你的第三個問題，再次推動我們的 BD 戰略的是我們在整個分支機構制定的長期戰略路線圖。所以如果你考慮一下，你提到了免疫學作為例子。我會說在免疫學方面，我們有兩個我們正在努力推動的基本目標。在免疫學領域仍有一些領域，我們相信我們可以顯著提高用於患者的療法的有效性，以推動更高水平的緩解或更高水平的內窺鏡癒合。換句話說，在我們所處的領域內獲得更好的臨床結果。因此，我們在這些領域付出了巨大的努力來帶來下一代資產，或者正如湯姆在他的評論中提到的那樣，有機會將兩者結合起來機制共同實現該水平的治療益處。

And then we look outside those areas at the adjacencies. And we look for where are the opportunities for us to be able to bring in either an existing mechanism or something we can either develop within our own discovery group or something that we can acquire on the outside as a mechanism that we don't currently have. But we tend to look for where there are areas of large unmet needs and relatively significant patient populations.

然後我們看看這些區域之外的鄰接區域。我們尋找機會讓我們能夠引入現有機製或我們可以在我們自己的發現小組內開發的東西或我們可以在外部獲得的東西作為我們目前沒有的機制.但我們傾向於尋找存在大量未滿足需求和相對大量患者群體的區域。

So I use two examples to illustrate. Vitiligo. Vitiligo is a disease that's very prevalent. There aren't good therapeutic options in it today at all. We do believe there are mechanisms that will allow you to effectively treat vitiligo. If those are effective, that could be a very significant opportunity over time. Alopecia is another good example of that. So that's how we focus BD in these areas. That's not to say we would never look at a more niche opportunity or an orphan opportunity, but I wouldn't say orphan is something that is core to our strategy.

所以我用兩個例子來說明。白癜風。白癜風是一種非常普遍的疾病。今天根本沒有好的治療選擇。我們確實相信有一些機制可以讓您有效地治療白斑病。如果這些有效，那麼隨著時間的推移，這可能是一個非常重要的機會。脫髮是另一個很好的例子。這就是我們將 BD 重點放在這些領域的方式。這並不是說我們永遠不會考慮更多的利基機會或孤兒機會，但我不會說孤兒是我們戰略的核心。

It comes from Robyn Karnauskas with Truist.

它來自 Robyn Karnauskas 和 Truist。

It was great with all the color you've given. I just had some -- I want to follow up on, you mentioned Vitiligo. With the competition with topical rux, which might have a first mover advantage and then they have an oral as well in Pfizer. How do you see the opportunity for you in vitiligo for RINVOQ? Can it compete?

你給的所有顏色都很棒。我剛吃了一些——我想跟進，你提到了白斑病。隨著外用 rux 的競爭，這可能具有先發優勢，然後他們在輝瑞公司也有口服。您如何看待 RINVOQ 治療白斑病的機會？它能競爭嗎？

And then my second question last earnings call, you highlighted your GARP TGF-beta. So that's 151. And I know there's been a lot of cardiotox in the space. So what gives you some confidence what features and what indications, like how do you focus on this? And how do you view the competition profile?

然後是我在上次財報電話會議上提出的第二個問題，你強調了你的 GARP TGF-beta。那是 151。我知道這個領域有很多心臟毒素。那麼，是什麼讓您有信心，哪些功能和哪些跡象，比如您如何專注於此？您如何看待競爭概況？

On vitiligo, maybe Jeff and I will tag team on it. I would certainly say a topical has a place, but it is difficult for people that have large areas of their bodies that are impacted by something like vitiligo for a topical to be a manageable therapy for those patients. So an oral for those patients that have more severe disease typically has greater benefit and frankly, better compliance among those patients, which ultimately gives you better clinical outcomes. So I think the RINVOQ will stack up against whoever the competitive alternatives are based on the data. Based on how we've seen RINVOQ perform in other areas, I think we feel pretty good about what the potential is. But the data will speak for itself, see what the data looks like.

關於白癜風，也許傑夫和我會標記團隊。我肯定會說外用藥物有一席之地，但對於身體大面積受到白斑病等疾病影響的人來說，外用藥物很難成為對這些患者可控的治療方法。因此，對於那些患有更嚴重疾病的患者來說，口服通常會帶來更大的好處，坦率地說，這些患者的依從性更好，最終會給你帶來更好的臨床結果。因此，我認為 RINVOQ 將與基於數據的競爭替代品相抗衡。基於我們看到 RINVOQ 在其他領域的表現，我認為我們對潛力感到非常滿意。但數據會說明一切，看看數據是什麼樣子的。

Jeff and Tom, would you add anything?

傑夫和湯姆，你們能補充點什麼嗎？

Just to build on that. When we look at the valuation of, for example, that indication or HS or alopecia, which again are those derm oriented indications that will follow on pretty quickly in the middle of the decade on top of atopic dermatitis. We do exactly what Rick highlighted. We will segment the patients based on the body surface area. We know that the topicals will be important for a certain percentage of population. For example, if it's maybe highly located to the face, that might be more appropriate, at least as the first course of action.

只是以此為基礎。例如，當我們查看該適應症或 HS 或脫髮的估值時，這些又是那些以皮膚為導向的適應症，將在本世紀中期繼特應性皮炎之後很快出現。我們完全按照里克強調的去做。我們將根據體表面積對患者進行細分。我們知道，主題對於一定比例的人口來說很重要。例如，如果它可能位於面部的高度位置，那可能更合適，至少作為第一個行動方案。

But we do believe that in almost all indications that we've looked at for RINVOQ, it just performs exceptionally well in the clinic. And we would anticipate that as well above a base case scenario. Perfect example is Crohn's disease. There will not be another JAK inhibitor in Crohn's disease for the United States just because they just don't work. And you have spectacular results with the selective JAK with RINVOQ. So we take that all into that competitive context all into our calculations as we look forward to return for those future derm indications.

但我們確實相信，在我們為 RINVOQ 研究過的幾乎所有適應症中，它在臨床上的表現都非常出色。我們預計這也會高於基本情況。克羅恩病就是一個很好的例子。美國不會有另一種 JAK 抑製劑用於治療克羅恩病，因為它們根本不起作用。使用帶有 RINVOQ 的選擇性 JAK，您將獲得驚人的結果。因此，我們將所有這些都納入到競爭環境中，所有這些都納入我們的計算中，因為我們期待著返回這些未來的皮膚適應症。

If I can just continue with vitiligo. I mean, we will have readouts for our Phase II study this year, and we've mostly been looking at those cases where there's more extensive body coverage disease or the face. So I think it would be a different -- it's a much better to take an oral than a cream when you actually have significant body coverage. Again, we'll see the data, we will report on another quarter call. .

如果我能繼續治療白癜風。我的意思是，我們今年將獲得 II 期研究的讀數，我們主要關注那些覆蓋更廣泛的身體或面部疾病的病例。所以我認為這會有所不同——當你實際上有大量的身體覆蓋時，口服比乳霜好得多。同樣，我們將看到數據，我們將在另一個季度電話會議上報告。 .

Thank you, Robyn, for the second question. Yes, TGF-beta is a known tumor suppressive pathway and people have tried to drug it to increase the response to immunotherapies. The first-generation TGF-beta because the target is so many parts of the body, you actually have effects, the cardiovascular effects having related to the TGF-beta activity in some of the endothelial cells in the valves and so on of the heart.

羅賓，謝謝你提出第二個問題。是的，TGF-beta 是一種已知的腫瘤抑制途徑，人們已嘗試對其進行藥物治療以增加對免疫療法的反應。第一代 TGF-beta 因為目標是身體的很多部位，所以你實際上有影響，心血管影響與心臟瓣膜等內皮細胞的一些內皮細胞中的 TGF-beta 活性有關。

Here, we're using GARP as our target. GARP is actually a receptor for TGF-beta that's called latent inactive that GARP is found only on Treg cells, a little bit on some fiber some store sales, but it's not some in the heart or other tissues. That's what gives us our safety profile and the ability to causing a suppression on Treg cells found in tumor cells as opposed to other places in the body. So that we felt from the beginning was the attribute we needed to go to target this pathway would be something that will be tumor selective and that's what we've been able to see so far.

在這裡，我們使用 GARP 作為我們的目標。 GARP 實際上是 TGF-beta 的一種受體，它被稱為潛在的非活性，GARP 只存在於 Treg 細胞上，一些纖維上有一些商店銷售，但它不是一些在心臟或其他組織中。這就是我們的安全概況和抑制腫瘤細胞而非身體其他部位 Treg 細胞的能力。所以我們從一開始就覺得我們需要去瞄準這個途徑的屬性將是腫瘤選擇性的東西，這就是我們迄今為止能夠看到的。

She asked about what tumors potentially.

她詢問可能是什麼腫瘤。

What tumors? So in our -- initially, we focused on tumors. So this pathway is found on almost every solid tumor has some subset tumors, which express TGF-beta and GARP. We started off thinking that we'd do a Phase I safety study, which we did well that we will expand. And we had picked liver and bladder because we saw a lot of TGF-beta pathway in those indications. And we also -- although we knew there was 7 CRC, we saw in patients in our Phase I study, which were unselected in terms of tumor type. We saw responses.

什麼腫瘤？所以在我們 - 最初，我們專注於腫瘤。因此，幾乎每個實體瘤都有一些表達 TGF-β 和 GARP 的亞型腫瘤，因此發現該通路。我們開始考慮進行第一階段的安全研究，我們做得很好，我們將擴大。我們選擇了肝臟和膀胱，因為我們在這些適應症中看到了很多 TGF-β 通路。我們也——雖然我們知道有 7 個 CRC，但我們在第一階段研究中看到了患者，這些患者在腫瘤類型方面沒有被選擇。我們看到了回應。

So we've actually continued expanding studying CRC, but we did see responses in liver cancer where we expected to see it based on expression of TGF-beta. We did see it in bladder cancer, and we're expanding in those indications at this point.

所以我們實際上繼續擴大了對 CRC 的研究，但我們確實看到了肝癌的反應，我們希望看到它基於 TGF-β 的表達。我們確實在膀胱癌中看到了它，目前我們正在擴大這些適應症。

Given the fact that I said earlier that we TGF-beta in all types of tumors, both tumors called hot or cold, we're actually expanding in other tumors to get signals right now. And again, we have we'll have baskets to actually continue to explore its indication space. But right now, we're expanding when we're going to Phase II dose rating studies that's indications where we've actually seen data in our Phase I study.

鑑於我之前說過我們在所有類型的腫瘤中都使用 TGF-beta，這兩種腫瘤都稱為熱腫瘤或冷腫瘤，我們實際上正在其他腫瘤中進行擴展以立即獲取信號。再一次，我們將有籃子來實際繼續探索其指示空間。但是現在，當我們進行 II 期劑量評級研究時，我們正在擴大，這表明我們在 I 期研究中實際看到了數據。

It comes from Simon Baker with Redburn.

它來自 Simon Baker 和 Redburn。

Two, if I may, please. Just going back to U.S. HUMIRA. Giving us the expected erosion is extremely helpful. It's also extremely impressive that you confident enough to give a point estimate for the percentage erosion in '23. So notwithstanding that, I wonder if you could give us what the likely pushes and pulls are? Is this something where we should be thinking more about the being upside risk due to inability of those additional generics biosimilars to supply the market. So any color on pushes and pulls there and also into 2024 and your confidence around the erosion curve in '24?

兩個，如果可以的話，請。剛回到美國 HUMIRA。給我們預期的侵蝕是非常有幫助的。同樣令人印象深刻的是，您有足夠的信心對 23 年的侵蝕百分比進行點估計。所以儘管如此，我想知道你能否告訴我們可能的推動和拉動是什麼？這是我們應該更多地考慮由於那些額外的仿製藥生物仿製藥無法供應市場而帶來的上行風險嗎？因此，任何顏色都會推動和拉動到 2024 年，您對 24 年的侵蝕曲線有信心嗎？

And then a question on tax. One question topic that's been raised by some of your peers has been an impact from the OECD minimum global tax rate initiatives in '23. Your guidance would suggest that isn't a factor for you. I just wonder if you could give us any color on when and if you expect those initiatives to impact your tax rate?

然後是關於稅收的問題。一些同行提出的一個問題主題是 23 年經合組織最低全球稅率倡議的影響。您的指導建議這對您來說不是一個因素。我只是想知道您是否可以告訴我們您何時以及是否希望這些舉措會影響您的稅率？

Simon, this is Rob. I'll take your first question. So when we give guidance, we typically give approximate assumptions, and we do use point estimates. We don't typically give product level range. So it has been our practice. So we said approximately 37% erosion for U.S. HUMIRA. We have confidence in that number, obviously. But I think in terms of the pushes and pulls, it's really going to be about volume erosion, right? I think that's -- if you think over the course of the year, we made assumptions around volume erosion. We have good visibility of the price. Now it's a question of what will the volume erosion look like? And obviously, as we go through the year, we'll update you on that.

西蒙，這是羅伯。我會回答你的第一個問題。所以當我們給出指導時，我們通常會給出近似的假設，我們確實會使用點估計。我們通常不提供產品級別範圍。所以這一直是我們的做法。所以我們說美國 HUMIRA 的侵蝕約為 37%。顯然，我們對這個數字有信心。但我認為就推動和拉動而言，這真的與體積侵蝕有關，對吧？我認為那是——如果你考慮一年中的情況，我們會圍繞成交量侵蝕做出假設。我們對價格有很好的了解。現在的問題是體積侵蝕會是什麼樣子？顯然，隨著我們度過這一年，我們會向您介紹最新情況。

This is Scott. I'll give you some thoughts on the OECD question that you asked regarding tax. So you're right. For 2023, we do not see any impact from this. In our view, there's a lot of things to be worked out with respect to the global minimum tax you mentioned. We have, in the U.S., as you know, a minimum tax we see ultimately this OECD tax being a top-up on that if that does occur, but there's a lot of details to be worked out, and we wouldn't anticipate any impact there until 2025, if there is an impact.

這是斯科特。對於您提出的有關稅收的經合組織問題，我將給您一些想法。所以你是對的。對於 2023 年，我們認為這不會產生任何影響。我們認為，關於你提到的全球最低稅，還有很多事情需要解決。如您所知，我們在美國有最低稅，我們最終會看到，如果確實發生這種情況，經合組織的稅收將是對此的補充，但還有很多細節需要解決，我們預計不會有任何影響到 2025 年，如果有影響的話。

It comes from Navann Ty with BNP Paribas.

它來自 BNP Paribas 的 Navann Ty。

I have three quick follow-ups, please. The first one on aesthetics, in addition to the macro impact, are you seeing or do you expect increasing competition from your smaller competitors, DTC campaigns and new products?

我有三個快速跟進，請。第一個關於美學的問題，除了宏觀影響之外，您是否看到或預計來自較小的競爭對手、DTC 活動和新產品的競爭會越來越激烈？

The second question is on HUMIRA. Was AMGEVITA pricing in line with your expectation? And the third follow-up is on capital allocation. So can we think of 2x as a soft net leverage target, which is relevant for AbbVie to consider material business development?

第二個問題是關於 HUMIRA 的。 AMGEVITA 的定價是否符合您的預期？第三個後續是資本配置。那麼我們是否可以將 2 倍視為軟淨槓桿目標，這與 AbbVie 考慮重大業務發展相關？

Carrie?

嘉莉？

I'll take that first question on aesthetic competition. So in terms of U.S. Botox Cosmetics, this is a product that's around for 20 years and has based increased competition and still commands market-leading -- market share in the high 60s. And we know though that the competitive market will expand as new entrants are coming and have entered and in terms of a revamped toxin at the end of last year.

我將回答關於審美競爭的第一個問題。因此，就 U.S. Botox Cosmetics 而言，這是一款已有 20 年曆史的產品，基於日益激烈的競爭，仍然佔據市場領先地位——市場份額高達 60 年代。而且我們知道，隨著新進入者的到來和進入以及去年年底改進後的毒素，競爭市場將會擴大。

What we've seen in the aesthetics market is that, of course, customers are going to try these new products. It's highly kind of newness driven, and there's a novelty factor and trial and competitive trial is to be expected. And what we see is that these products and past aesthetic launches that we've watched, the share ramps for the first 12 to 18 months and then tends to stabilize. And so of course, we don't underestimate any of our competitors. And so in 2023, we are modeling what we think is a competitive amount of share erosion in terms of our Botox business. And we'd expect that in '23 and beyond that U.S. Botox Cosmetic will continue to be the clear #1 market leader. And the new toxins that enter the market will be competing for their position #2, 3 or 4 in our customers' offices.

我們在美容市場看到的是，客戶當然會嘗試這些新產品。這是一種高度的新奇驅動，並且有一個新奇的因素和試驗和競爭試驗是可以預期的。我們看到的是，我們觀察到的這些產品和過去的美學發布，份額在前 12 到 18 個月上升，然後趨於穩定。當然，我們不會低估我們的任何競爭對手。因此，在 2023 年，我們正在對我們認為在保妥適業務方面具有競爭力的份額侵蝕進行建模。我們預計，在 23 世紀及以後，美國保妥適化妝品公司將繼續成為明確的第一市場領導者。進入市場的新毒素將在我們客戶的辦公室中爭奪其第 2、3 或 4 的位置。

And it's Jeff. On your comment on AMGEVITA, the range of pricings that were released were not really a surprise. There's been some external thoughts that this is of interest where there were two different AMGEVITAs, one high WACC and one low WACC. But again, we've seen this across very different categories and studied it very carefully, as you would expect.

是傑夫。關於您對 AMGEVITA 的評論，所發布的定價範圍並不令人意外。有一些外部想法認為這很有趣，因為有兩種不同的 AMGEVITA，一種是高 WACC，一種是低 WACC。但同樣，正如您所期望的那樣，我們已經在非常不同的類別中看到了這一點，並且非常仔細地研究了它。

So we've seen variably priced WACC products in our own HCV market with authorized generics from competitors. We've seen it in the diabetes space across multiple competitors, including biosimilar competitors. And certainly, with the -- with Amgen and the other segments of their own business. They were often moving around the list prices as well. So all in all, within the range that we would expect from AMGEVITA. Yes.

因此，我們在我們自己的 HCV 市場上看到了價格可變的 WACC 產品，以及來自競爭對手的授權仿製藥。我們已經在多個競爭對手（包括生物仿製藥競爭對手）的糖尿病領域看到了它。當然，與 - Amgen 和他們自己業務的其他部門。他們也經常圍繞標價變動。所以總而言之，在我們對 AMGEVITA 的期望範圍內。是的。

This is Rob. I'll take the question on net leverage. So the 2x is -- think about it as our sustainable target. So as long as there's a path back to net leverage of 2x, could take us in some cases, it could take 2 to 3 years to get back to that. But as long as there's a path, a very clear path to get back to net leverage of 2x, that's the best way to think about how we would evaluate it.

這是羅布。我回答有關淨槓桿的問題。所以 2x 是——將其視為我們的可持續目標。因此，只要有回到 2 倍淨槓桿的途徑，在某些情況下我們可能需要 2 到 3 年才能回到那個水平。但只要有一條路徑，一條非常明確的路徑可以回到 2 倍的淨槓桿率，這就是考慮我們如何評估它的最佳方式。

Our final question will come from Gavin Clark-Gartner with Evercore ISI.

我們的最後一個問題將來自 Evercore ISI 的 Gavin Clark-Gartner。

Wanted to confirm if you were planning to submit the Imbruvica plus Venclexta frontline CLL combination to the FDA following the ASH this year? And then on 951 in Parkinson's, we saw top line data from competitors from last month. I don't have the full data yet. One thing that sticks out is that they have lower discontinuation rates. So just wondering if there's any insight on devices or trial design that may explain this.

想確認您是否計劃在今年的 ASH 之後向 FDA 提交 Imbruvica 加 Venclexta 一線 CLL 組合？然後在帕金森氏症的 951 上，我們看到了競爭對手上個月的頂級數據。我還沒有完整的數據。突出的一件事是它們的停藥率較低。所以只是想知道是否有任何關於設備或試驗設計的見解可以解釋這一點。

It's Roopal. I'll take those. So for the I plus that you referenced, we have that in Europe, and I think you're talking about the ASH data, overall survival. There as it clears couple of years is 0.5% or less and the PFS still stays low. At this time, we're not submitting here at the FDA. They would like to see a little more prospective data in another trial setting. So that's the I plus V.

是魯帕爾。我會拿那些。所以對於你提到的 I 加，我們在歐洲有，我認為你在談論 ASH 數據，即總生存期。幾年後它清除了 0.5% 或更少，PFS 仍然很低。目前，我們不在 FDA 提交。他們希望在另一個試驗環境中看到更多的前瞻性數據。這就是 I 加 V。

On 951, this is interesting on the competitors you bring up. So the -- when you run these patients in, you could have discontinuation rates. And if you include them or not include them, it's going to impact what happens post run in. So for example, when you see our data set, we count the run-in discontinuation and post run-in as you get into the main part of the trial. So you see that in the 20 percentile range or so. And that's fairly consistent with what you would see with a subcutaneous 24 hour infusion. And it's not clear to us how that data, as you're speaking about is reported.

在 951 上，這對您提出的競爭對手很有趣。所以——當你讓這些病人進來時，你可能會有停藥率。如果你包括或不包括它們，它會影響運行後發生的事情。例如，當你看到我們的數據集時，我們會在你進入主要部分時計算運行中斷和運行後的審判。所以你在 20 個百分點左右的範圍內看到了這一點。這與您在皮下 24 小時輸液中看到的結果相當一致。我們不清楚您所說的數據是如何報告的。

Also, we don't know if that's more than one injection is that two injections and is it rotated daily. I can tell you about 951. We have dosing exposure that gets up to DUOPA unique from DUOPA to 24 hours. It's a single injection, and you can leave it in for 72 hours.

此外，我們不知道是否不止一次注射是兩次注射，是否每天輪換一次。我可以告訴您有關 951 的信息。我們的劑量暴露可以達到 DUOPA 獨特的 DUOPA 到 24 小時。這是單次注射，您可以將其放置 72 小時。

Thanks, Gavin. That concludes today's conference call. If you'd like to listen to a replay of the call, please visit our website at investors.abbvie.com. Thanks again for joining us.

謝謝，加文。今天的電話會議到此結束。如果您想收聽通話重播，請訪問我們的網站 investors.abbvie.com。再次感謝您加入我們。

This does conclude today's conference call. We thank you all for participating. You may now disconnect, and have a great rest of your day.

這確實結束了今天的電話會議。感謝大家的參與。您現在可以斷開連接，好好休息一天。