艾伯維 (ABBV) 2022 Q3 法說會逐字稿

Good morning, and thank you for standing by. Welcome to the AbbVie Third Quarter 2022 Earnings Conference Call. (Operator Instructions)

早上好，感謝您的支持。歡迎參加艾伯維 2022 年第三季度收益電話會議。 （操作員說明）

I would now like to introduce Ms. Liz Shea, Vice President, Head of Investor Relations.

我現在想介紹一下副總裁兼投資者關係主管 Liz Shea 女士。

Good morning, and thanks for joining us.

早上好，感謝您加入我們。

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; and Tom Hudson, Senior Vice President, R&D and Chief Scientific Officer. Joining us for the Q&A portion of the call are Carrie Strom, Senior Vice President and President, Global Allergan Aesthetics; Scott Reents, Senior Vice President and Chief Financial Officer; Neil Gallagher, Vice President, Development and Chief Medical Officer; and Roopal Thakkar, Vice President, Global Regulatory Affairs.

今天與我通話的還有董事會主席兼首席執行官 Rick Gonzalez； Rob Michael，副主席兼總裁； Jeff Stewart，執行副總裁兼首席商務官；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環節的還有艾爾建全球美學高級副總裁兼總裁 Carrie Strom； Scott Reents，高級副總裁兼首席財務官； Neil Gallagher，開發副總裁兼首席醫療官；以及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 for purposes of the Private Securities Litigation Reform Act of 1995. 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.

在我們開始之前，我要指出，我們今天所做的一些陳述可能被視為 1995 年《私人證券訴訟改革法案》的前瞻性陳述。艾伯維警告說，這些前瞻性陳述可能會受到風險和不確定性的影響。導致實際結果與前瞻性陳述中的結果大不相同。有關這些風險和不確定性的更多信息包含在我們提交給美國證券交易委員會的文件中。除法律要求外，艾伯維不承擔更新這些前瞻性陳述的義務。

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 comparable GAAP financial measures in our earnings release and regulatory filings from today, which can be found on our website.

在今天的電話會議上，非 GAAP 財務指標將用於幫助投資者了解 AbbVie 的業務表現。這些非公認會計原則財務指標與我們從今天開始的收益發布和監管文件中的可比公認會計原則財務指標相一致，可以在我們的網站上找到。

Following our prepared remarks, we'll take your questions. So with that, I'll now turn the call over to Rick.

在我們準備好的評論之後，我們將回答您的問題。因此，我現在將電話轉給 Rick。

Thank you, Liz. Good morning, everyone, and thank you for joining us today. I'll briefly comment on our overall performance, then Jeff, Tom and Rob will review our third quarter business highlights, pipeline progress and financial results in more detail.

謝謝你，麗茲。大家早上好，感謝您今天加入我們。我將簡要評論我們的整體業績，然後 Jeff、Tom 和 Rob 將更詳細地回顧我們第三季度的業務亮點、管道進展和財務業績。

AbbVie continues to perform very well, a testament to the strength of our broad, diversified portfolio. I'm especially pleased with the performance of our immunology assets, Skyrizi and Rinvoq. We delivered adjusted earnings per share of $3.66, exceeding our expectations. Total net revenues of $14.8 billion were up 5.4% on an operational basis, in line with our expectations.

艾伯維繼續表現出色，證明了我們廣泛、多元化的投資組合的實力。我對我們的免疫學資產 Skyrizi 和 Rinvoq 的表現特別滿意。我們的調整後每股收益為 3.66 美元，超出了我們的預期。運營基礎上的總淨收入為 148 億美元，增長 5.4%，符合我們的預期。

Immunology once again demonstrated impressive results, with Skyrizi and Rinvoq now on pace to deliver more than $7.5 billion in combined sales this year, well ahead of our initial expectations. This performance is especially encouraging, recognizing that we're in the early launch phase for both assets in IBD and PSA, as well as Rinvoq in atopic dermatitis.

Immunology 再次展示了令人印象深刻的成果，Skyrizi 和 Rinvoq 現在有望在今年實現超過 75 億美元的合併銷售額，遠遠超出我們最初的預期。這種表現尤其令人鼓舞，因為我們認識到 IBD 和 PSA 的資產以及特應性皮炎中的 Rinvoq 都處於早期推出階段。

Skyrizi and Rinvoq have established outstanding launch trajectories across existing and new indications, giving us a high degree of confidence in the collective potential of these 2 assets to ultimately exceed the peak revenues achieved by Humira, achieving the strategic objective we had for replacing Humira.

Skyrizi 和 Rinvoq 已經在現有和新的適應症中建立了出色的發布軌跡，使我們對這兩種資產的集體潛力充滿信心，最終超過 Humira 實現的峰值收入，實現了我們取代 Humira 的戰略目標。

We also saw a continued strong double-digit operational sales growth from several additional key products, including Botox Cosmetic, Vraylar, Venclexta and Botox Therapeutic. This strong momentum is helping us offset some of the interim economic pressure we now see in our Aesthetics portfolio. Based on these results, we remain confident in the outlook of our business and are reaffirming the midpoint of our full year 2022 EPS guidance at $13.86, which represents strong double-digit growth.

我們還看到其他幾個關鍵產品的營業銷售額持續強勁增長，包括 Botox Cosmetic、Vraylar、Venclexta 和 Botox Therapeutic。這種強勁的勢頭正在幫助我們抵消我們現在在美學產品組合中看到的一些臨時經濟壓力。基於這些結果，我們對我們的業務前景仍然充滿信心，並重申我們 2022 年全年每股收益指引的中點為 13.86 美元，這代表強勁的兩位數增長。

As many of you are aware, we have a leading consumer-facing Aesthetics portfolio, which is largely cash pay. We have been monitoring the global economic situation. Based on all the data we have been observing, especially in the U.S. with both the consumer confidence index and real personal consumption expenditures trending down and continued high inflation, these factors are putting pressure on consumers' discretionary spending. This metric correlates with a slowdown in treatment procedures that we're seeing across the Aesthetics markets, impacting the growth rates for toxins, fillers and body contouring.

你們中的許多人都知道，我們擁有領先的面向消費者的美學產品組合，主要是現金支付。我們一直在關注全球經濟形勢。根據我們一直觀察到的所有數據，特別是在美國，消費者信心指數和實際個人消費支出均呈下降趨勢，通脹持續高企，這些因素對消費者的可自由支配支出構成壓力。該指標與我們在整個美容市場看到的治療程序放緩相關，影響了毒素、填充劑和身體輪廓的增長率。

While our U.S. Aesthetics market share remains stable across both toxins and fillers, we now believe it's prudent to adjust our full year Aesthetics forecast to reflect the moderating market growth over the near to medium term, which is expected to predominantly impact Juvederm as well as our body contouring portfolio products, which represent higher price points for consumers.

雖然我們在毒素和填充劑方面的美國美容市場份額保持穩定，但我們現在認為調整我們的全年美容預測以反映中短期市場增長放緩是謹慎的做法，預計這將主要影響 Juvederm 以及我們的身體輪廓組合產品，對消費者來說代表更高的價格點。

While it's difficult to predict the duration of these economic dynamics, we expect these conditions to persist into 2023. As consumer confidence improves, we would once again expect the market growth to accelerate. Our Aesthetics portfolio experienced a rapid and sustained recovery following the 2008, 2009 recession, so we anticipate any impact will be transient.

雖然很難預測這些經濟動態的持續時間，但我們預計這些情況將持續到 2023 年。隨著消費者信心的改善，我們將再次預計市場增長將加速。在 2008 年和 2009 年經濟衰退之後，我們的美學產品組合經歷了快速且持續的複蘇，因此我們預計任何影響都將是短暫的。

Over the long term, the Aesthetics business continues to be an extremely attractive, underpenetrated market with significant growth potential. The current market dynamics do not change our long-term guidance for Aesthetics, and we remain confident in our ability to achieve total sales of more than $9 billion in 2029.

從長遠來看，美容業務仍然是一個極具吸引力、滲透率低的市場，具有巨大的增長潛力。當前的市場動態不會改變我們對美學的長期指導，我們仍然有信心在 2029 年實現超過 90 億美元的總銷售額。

I also want to provide a brief update on the outlook for 2023. With regards to the status of contracting for Humira, our intent has always been to maintain broad formulary access so that we can compete effectively with forthcoming biosimilars. We are making very good progress consistent with this objective, and are currently projecting formulary access for at least 80% of all U.S. covered lives. We expect this percentage to increase further as we conclude additional contract discussions between now and the end of the year. As a result, we anticipate strong access for U.S. Humira throughout 2023, and project biosimilars will share access as they become available. We will provide sales guidance for Humira on our fourth quarter call.

我還想簡要介紹一下 2023 年的前景。關於 Humira 的合同狀態，我們的意圖一直是保持廣泛的處方集訪問權，以便我們能夠有效地與即將推出的生物仿製藥競爭。我們在與這一目標一致的情況下取得了非常好的進展，目前預計至少 80% 的美國受保人可以使用處方集。隨著我們從現在到年底之間完成額外的合同討論，我們預計這一百分比將進一步增加。因此，我們預計美國 Humira 將在 2023 年獲得強大的准入權，並且項目生物仿製藥將在可用時共享准入權。我們將在第四季度電話會議上為修美樂提供銷售指導。

While we're not issuing 2023 guidance today, it is important to note that when we issue our EPS outlook, we expect the lower end of the range to represent [floor] earnings. So while it's possible 2023 could outperform our guidance regardless of the shape of the erosion curve, we don't anticipate 2024 earnings will be lower than the initial 2023 EPS guidance given the momentum and growth from another year of our ex-Humira portfolio, which is expected to more than offset any incremental Humira erosion in 2024. We know that many investors have an interest in the timing of AbbVie's [trough] earnings, whether that be 2023 or 2024. The guidance range will -- should provide and give investors additional clarity regarding our expectations for the company's floor EPS.

雖然我們今天沒有發布 2023 年指引，但重要的是要注意，當我們發布每股收益展望時，我們預計該範圍的下限將代表 [最低] 收益。因此，儘管無論侵蝕曲線的形狀如何，2023 年的表現都可能超過我們的指引，但鑑於我們前修美樂投資組合的另一年的勢頭和增長，我們預計 2024 年的收益不會低於最初的 2023 年每股收益指引，這預計將超過 2024 年任何增加的 Humira 侵蝕。我們知道，許多投資者對艾伯維（AbbVie）的 [谷底] 收益的時間感興趣，無論是 2023 年還是 2024 年。指導範圍將 - 應該提供並給予投資者額外明確我們對公司地板每股收益的預期。

In summary, we continue to deliver strong results and see numerous opportunities for our diverse portfolio to drive long-term growth. To that end, as noted in our news release today, we're announcing a 5% increase in our quarterly cash dividend from $1.41 per share to $1.48 per share, beginning with the dividend payable in February 2023. Since our inception, we have grown our quarterly dividend by 270%.

總而言之，我們繼續取得強勁的業績，並看到我們多樣化的投資組合有許多機會來推動長期增長。為此，正如我們今天的新聞稿中所述，我們宣布將季度現金股息從每股 1.41 美元增加到每股 1.48 美元，增加 5%，從 2023 年 2 月支付的股息開始。自成立以來，我們已經成長我們的季度股息增加了 270%。

With that, I'll turn the call over to Jeff for additional comments on our commercial highlights. Jeff?

有了這個，我將把電話轉給 Jeff，就我們的商業亮點發表更多評論。傑夫?

Thank you, Rick. We once again demonstrated strong and balanced growth across our Therapeutic portfolio this quarter. I'll start with Immunology, where we are well positioned for sustained leadership in this extremely attractive market.

謝謝你，瑞克。本季度，我們的治療產品組合再次表現出強勁而平衡的增長。我將從免疫學開始，我們在這個極具吸引力的市場中處於領先地位。

Total Immunology revenues were more than $7.6 billion, up 16.4% on an operational basis. We remain very excited about the long-term potential for Skyrizi and Rinvoq, which are already having a significant impact on AbbVie's growth and performance, contributing approximately $2.1 billion in combined sales this quarter, representing nearly 15% of total company net revenues.

免疫學總收入超過 76 億美元，在運營基礎上增長 16.4%。我們仍然對 Skyrizi 和 Rinvoq 的長期潛力感到非常興奮，它們已經對 AbbVie 的增長和業績產生了重大影響，本季度的合併銷售額約為 21 億美元，占公司總淨收入的近 15%。

Skyrizi continues to exceed our expectations. Global revenues were $1.4 billion, up 12% on a sequential basis. In psoriasis, Skyrizi is capturing nearly one out of every 2 new and switching patients in the U.S. biologic market, with our leading total prescription share increasing to approximately 27%. We have also achieved total market share leadership in a dozen key international markets, including Japan, Canada and France.

Skyrizi 繼續超出我們的預期。全球收入為 14 億美元，環比增長 12%。在銀屑病方面， Skyrizi 在美國生物製品市場幾乎每 2 名新患者和轉換患者中就有一名患者，我們領先的總處方份額增加到約 27%。我們還在日本、加拿大和法國等十幾個主要國際市場取得了總市場份額的領先地位。

Psoriatic arthritis is ramping very nicely, with an expected global sales contribution of approximately $500 million just this year. Our PSA performance is especially strong in the U.S. Dermatology segment, where we have already achieved 10% total market share.

銀屑病關節炎的發展非常好，預計僅今年的全球銷售額就達到約 5 億美元。我們的 PSA 表現在美國皮膚科領域尤為強勁，我們已經獲得了 10% 的總市場份額。

Lastly, our launch of Skyrizi for Crohn's disease in the U.S. is progressing very well. Early prescription trends as well as feedback from gastroenterologists has been overwhelmingly positive, especially given Skyrizi's convenient dosing and strong clinical profile. Importantly, commercial access for Skyrizi Crohn's is now equal to psoriasis and PSA, with sales in this indication expected to ramp significantly over the next several quarters. Given the momentum we are seeing across the indications, we will be raising our full year sales guidance once again for Skyrizi.

最後，我們在美國推出的治療克羅恩病的 Skyrizi 進展順利。早期的處方趨勢以及胃腸病學家的反饋都非常積極，特別是考慮到 Skyrizi 的方便給藥和強大的臨床特徵。重要的是，Skyrizi Crohn's 的商業准入現在與銀屑病和 PSA 相當，預計未來幾個季度該指標的銷售額將大幅增長。鑑於我們在各種跡像中看到的勢頭，我們將再次提高 Skyrizi 的全年銷售指導。

Turning now to Rinvoq, which delivered global sales of $695 million, demonstrating more than 17% sequential growth. We continue to see positive momentum in RA, with total market share increasing to more than 6% in both the U.S. and across key international geographies.

現在轉向 Rinvoq，其全球銷售額達到 6.95 億美元，環比增長超過 17%。我們繼續看到 RA 的積極勢頭，在美國和主要國際地區的總市場份額增加到 6% 以上。

Global prescriptions are also ramping nicely in PSA, ankylosing spondylitis and non-radiographic axial [spa], a testament to the strong clinical profile Rinvoq has demonstrated across the broader rheumatology segment. Rinvoq is now the only [JAK] inhibitor with global approval for all 4 major room indications.

全球處方在 PSA、強直性脊柱炎和非放射軸性 [spa] 方面也有很好的增長，這證明了 Rinvoq 在更廣泛的風濕病領域所展示的強大臨床特徵。 Rinvoq 現在是唯一獲得全球批准的所有 4 個主要房間適應症的 [JAK] 抑製劑。

In atopic dermatitis, we continue to see strong demand for Rinvoq, particularly in the second-line setting. U.S. in-play market share is tracking in line with our expectations, and we were making excellent progress internationally, with in-place share ranging now from approximately 20% to 35% across our major markets. AD remains a highly underpenetrated market globally and an attractive long-term growth opportunity for Rinvoq.

在特應性皮炎方面，我們繼續看到對 Rinvoq 的強勁需求，特別是在二線環境中。美國的遊戲市場份額符合我們的預期，我們在國際上取得了出色的進展，目前在我們主要市場的就地市場份額約為 20% 至 35%。 AD 在全球仍然是一個高度滲透的市場，對 Rinvoq 來說是一個有吸引力的長期增長機會。

Lastly, in ulcerative colitis, we are very excited by the early prescription trends in the U.S. In the second line plus setting, Rinvoq is already achieving the second highest in-place share, which is now approaching 20% in just a few months post launch. Physicians have been pleased with Rinvoq's high rates of endoscopic healing as well as the speed of onset. With over 70% of bioexperience UC patients currently on or having used TNF therapy, the second line plus opportunity for Rinvoq in UC is substantial. This strong adoption in UC among gastroenterologists is also encouraging for Rinvoq's potential in Crohn's disease as well. We are on track for U.S. and EMA regulatory decisions in the first half of 2023.

最後，在潰瘍性結腸炎方面，我們對美國的早期處方趨勢感到非常興奮。在二線加設置中，Rinvoq 已經實現了第二高的就地份額，在推出後的短短幾個月內就接近 20% .醫生對 Rinvoq 的高內窺鏡癒合率和發病速度感到滿意。超過 70% 的生物經驗 UC 患者目前正在接受或曾經使用 TNF 治療，因此 Rinvoq 在 UC 中的二線和機會是巨大的。 UC 在胃腸病學家中的廣泛採用也鼓舞了 Rinvoq 在克羅恩病中的潛力。我們有望在 2023 年上半年做出美國和 EMA 監管決定。

Global Humira sales were approximately $5.6 billion, up 3.9% on an operational basis with 7.4% growth in the U.S., partially offset by international performance where revenues were down 16.8% operationally due to biosimilar competition.

全球 Humira 銷售額約為 56 億美元，在運營基礎上增長 3.9%，在美國增長 7.4%，部分被國際業績所抵消，由於生物仿製藥競爭，運營收入下降 16.8%。

Turning now to Hematologic Oncology, where total revenues were $1.65 billion, down 9.9% on an operational basis. Imbruvica global revenues were approximately $1.1 billion, down 17.4%. The U.S. performance continues to be impacted by an incrementally challenging CLL market, with new patient starts down approximately 20% relative to pre-COVID levels.

現在轉向血液腫瘤學，其總收入為 16.5 億美元，在運營基礎上下降 9.9%。 Imbruvica 的全球收入約為 11 億美元，下降 17.4%。美國的表現繼續受到日益具有挑戰性的 CLL 市場的影響，新患者的入院率相對於 COVID 之前的水平下降了約 20%。

Given the U.S. CLL market has been consistently lower than our expectation in the past several quarters, we are now reducing our view of the total size of the addressable patient population for this indication going forward. We also anticipate further share erosion following the recent unfavorable change to the NCCN guideline preference for Imbruvica in CLL as well as increasing existing and new competition. These market and share dynamics are expected to have a flow-through impact on Imbruvica's 2023 performance.

鑑於美國 CLL 市場在過去幾個季度一直低於我們的預期，我們現在正在降低我們對未來這一適應症的可尋址患者群體總規模的看法。我們還預計，在最近 NCCN 指南對 CLL 中 Imbruvica 的偏好發生不利變化以及現有和新的競爭增加之後，份額會進一步下降。預計這些市場和份額動態將對 Imbruvica 2023 年的業績產生直接影響。

Venclexta global sales were [$515 million], up 11.3% on an operational basis. Continued share gains across both approved indications are being partially offset by a softer CLL market in the U.S. and a higher foreign exchange impact on international revenues. As a result, we will be adjusting our full year sales guidance for Venclexta.

Venclexta 的全球銷售額為 [5.15 億美元]，在運營基礎上增長 11.3%。美國 CLL 市場疲軟和外匯對國際收入的影響增加，部分抵消了這兩項獲批跡象的持續份額增長。因此，我們將調整 Venclexta 的全年銷售指導。

Longer term, we anticipate our Oncology portfolio will return to growth, driven by several promising new products and indications such as epcoritamab for DLBCL and follicular lymphoma, Venclexta new indications for multiple myeloma and high-risk MDS, navitoclax for myelofibrosis and Teliso-V for non-squamous non-small cell lung cancer. We are beginning to launch preparedness activities for several of these important opportunities and look forward to bringing new treatment options to patients.

從長遠來看，我們預計我們的腫瘤學產品組合將恢復增長，這將受到幾個有前途的新產品和適應症的推動，例如用於 DLBCL 和濾泡性淋巴瘤的 epcoritamab、用於多發性骨髓瘤和高風險 MDS 的 Venclexta 新適應症、用於骨髓纖維化的 navitoclax 和用於治療骨髓纖維化的 Teliso-V非鱗狀非小細胞肺癌。我們開始為其中幾個重要機會啟動準備活動，並期待為患者帶來新的治療選擇。

In Neuroscience, revenues were nearly $1.7 billion, up 8.3% on an operational basis. Vraylar once again delivered strong growth. Sales of $554 million were up 20.2% on an operational basis, reflecting continued market share momentum. We continue to anticipate the regulatory approval and the commercial launch of Vraylar as an adjunctive treatment for major depressive disorder this quarter, which would make Vraylar the only antipsychotic as a dual partial agonist approved to treat the most common forms of depression, both Bipolar I and adjunctive MDD.

在神經科學領域，收入接近 17 億美元，在運營基礎上增長 8.3%。 Vraylar 再次實現強勁增長。銷售額為 5.54 億美元，在運營基礎上增長 20.2%，反映了持續的市場份額勢頭。我們繼續期待本季度 Vraylar 的監管批准和商業推出，作為重度抑鬱症的輔助治療，這將使 Vraylar 成為唯一被批准用於治療最常見形式抑鬱症的抗精神病藥物，包括雙相 I 和輔助MDD。

Within migraine, our market-leading oral CGRP portfolio contributed $222 million in combined sales this quarter. Ubrelvy prescriptions increased high digit sequentially, while total revenues were unfavorably impacted by a one-time prior period accrual adjustment of $40 million related to patient access program costs. Excluding this one-time adjustment, Ubrelvy sales were up more than 20% versus the prior year.

在偏頭痛領域，我們市場領先的口服 CGRP 產品組合本季度的總銷售額為 2.22 億美元。 Ubrelvy 處方連續高位增長，而總收入受到與患者訪問計劃成本相關的前一期 4000 萬美元的一次性應計調整的不利影響。排除這一一次性調整，Ubrelvy 的銷售額比上一年增長了 20% 以上。

Qulipta revenues nearly doubled sequentially as we continue to make very good progress with commercial access. Potential label expansion in the U.S. as a preventative treatment in patients with chronic migraine and new therapy approvals in Europe represent additional opportunities to support Qulipta's strong momentum.

Qulipta 收入環比增長近一倍，因為我們在商業准入方面繼續取得非常好的進展。在美國作為慢性偏頭痛患者預防性治療的潛在標籤擴展和歐洲新療法的批准代表了支持 Qulipta 強勁勢頭的額外機會。

Botox Therapeutic is also performing very well with total sales of $699 million, up 10% on an operational basis. In chronic migraine, which accounts for roughly 45% of our therapeutic sales, Botox remains a foundational preventative treatment and the clear branded leader for existing as well as new patient starts.

Botox Therapeutic 的表現也非常出色，總銷售額為 6.99 億美元，在運營基礎上增長了 10%。在約占我們治療銷售額 45% 的慢性偏頭痛中，肉毒桿菌毒素仍然是一種基礎性的預防性治療方法，並且是現有和新患者開始的明確品牌領導者。

Lastly, our launch preparations are underway for ABBV-951, a potentially transformative next-generation therapy for advanced Parkinson's. We anticipate approval in the first half of next year and believe 951 has the potential to achieve peak sales in excess of $1 billion. So overall, I'm very pleased with the momentum across the Therapeutic portfolio, which is demonstrating strong revenue growth.

最後，我們正在為 ABBV-951 的推出做準備，這是一種潛在的變革性下一代晚期帕金森氏症療法。我們預計在明年上半年獲得批准，並相信 951 有可能實現超過 10 億美元的峰值銷售額。總體而言，我對整個治療組合的勢頭感到非常滿意，這表明收入增長強勁。

And with that, I'll turn the call over to Tom for additional comments on our R&D programs.

有了這個，我將把電話轉給湯姆，以徵求對我們研發計劃的更多評論。

Thank you, Jeff. In the area of Immunology, we had several important regulatory milestones since our last earnings call, receiving FDA approval for Rinvoq in non-radiographic axial [spa] and positive CHMP opinion for Skyrizi in Crohn's disease. These developments demonstrate the continued progress we are making with a global indication expansion of our next-generation immunology assets.

謝謝你，傑夫。在免疫學領域，自上次財報電話會議以來，我們取得了幾個重要的監管里程碑，獲得 FDA 對 Rinvoq 在非放射軸 [spa] 的批准以及對 Skyrizi 在克羅恩病中的積極 CHMP 意見。這些發展表明我們在全球適應症擴展我們的下一代免疫學資產方面取得的持續進展。

In the quarter, we also saw a longer term data from our Phase II study for Rinvoq in systemic lupus, where strong responses and flare reductions continued through 48 weeks of treatment. Based on these results, we plan to advance Rinvoq development in this indication, and we'll be discussing our Phase III program with regulatory agencies in the coming months.

在本季度，我們還看到了來自 Rinvoq 在系統性狼瘡中的 II 期研究的長期數據，在 48 週的治療中，強烈的反應和耀斑減少持續。基於這些結果，我們計劃在這一適應症中推進 Rinvoq 的開發，我們將在未來幾個月內與監管機構討論我們的 III 期計劃。

Now, I'd like to provide a few updates on our earlier-stage immunology pipeline. We recently began a Phase II study in ulcerative colitis for our RIPK1 inhibitor, ABBV-668. This small molecule inhibitor is designed to address chronic inflammatory diseases by preventing necroptosis and reducing TLR4 driven inflammation. This could be a differentiated approach that has the potential to provide significantly improved efficacy to patients suffering from ulcerative colitis. We look forward to providing updates as the data mature.

現在，我想提供一些關於我們早期免疫學管道的更新。我們最近開始了一項針對我們的 RIPK1 抑製劑 ABBV-668 的潰瘍性結腸炎 II 期研究。這種小分子抑製劑旨在通過預防壞死性凋亡和減少 TLR4 驅動的炎症來治療慢性炎症性疾病。這可能是一種差異化的方法，有可能為患有潰瘍性結腸炎的患者提供顯著改善的療效。隨著數據的成熟，我們期待提供更新。

Turning now to ABBV-154, our anti-TNF steroid conjugate, which is being evaluated in multiple indications. We recently completed the primary analysis for the Phase II dose-ranging study in RA patients. The hypothesis for this program was that by delivering the steroid directly to the site of inflammation, you could drive higher rates of efficacy with limited or no effects of systemic steroid exposure. In this study, all doses of 154 met the primary endpoint of ACR50 as well as the majority of secondary endpoints at week 12. At the medium and high doses, 154 delivered ACR scores that are similar to Rinvoq or slightly better, which validates the platform's ability to drive high levels of efficacy.

現在轉向 ABBV-154，我們的抗 TNF 類固醇偶聯物正在對多種適應症進行評估。我們最近完成了 RA 患者 II 期劑量範圍研究的初步分析。該計劃的假設是，通過將類固醇直接輸送到炎症部位，您可以在全身類固醇暴露有限或沒有影響的情況下提高療效。在這項研究中，154 的所有劑量均在第 12 周達到了 ACR50 的主要終點以及大多數次要終點。在中高劑量時，154 的 ACR 分數與 Rinvoq 相似或略高，這驗證了該平台的驅動高水平功效的能力。

The safety profile for 154 was generally consistent with the safety profile for adalimumab. As part of our safety assessment in this study, we analyzed metabolic parameters, including cortisol levels. The data showed minor decreases in cortisol levels at higher exposures, which are consistent with evidence of systemic steroid effects. Given the number of effective therapies available in RA and a more limited use of steroids in these patients, we do not plan to move forward in development for the RA indication.

154 的安全性概況與阿達木單抗的安全性概況基本一致。作為本研究安全評估的一部分，我們分析了代謝參數，包括皮質醇水平。數據顯示，在較高暴露量下皮質醇水平略有下降，這與全身性類固醇作用的證據一致。鑑於 RA 中可用的有效療法的數量以及在這些患者中類固醇的使用更為有限，我們不打算繼續開發 RA 適應症。

However, we continue to believe 154 has the potential to provide a benefit in other diseases, such as PMR and Crohn's disease, where steroid use is part of the typical treatment paradigm. Our exploratory Phase II studies in these 2 indications are ongoing, and we expect to see data from the PMR study in 2023 and from the Crohn's study in 2024.

然而，我們仍然相信 154 有可能為其他疾病帶來益處，例如 PMR 和克羅恩病，其中類固醇的使用是典型治療模式的一部分。我們對這兩個適應症的 II 期探索性研究正在進行中，我們希望看到 2023 年 PMR 研究和 2024 年克羅恩研究的數據。

Also in the area of Immunology, we recently made the decision to stop the clinical studies and discontinued development for ABBV-157, our RORgamma t inverse agonist. This decision was made due to new findings observed in our preclinical chronic toxicology study.

同樣在免疫學領域，我們最近決定停止臨床研究並停止開發我們的 RORgamma t 反向激動劑 ABBV-157。這一決定是由於我們在臨床前慢性毒理學研究中觀察到的新發現而做出的。

Moving now to our Oncology portfolio, where we continue to make excellent progress across all stages of our pipeline. We recently submitted our regulatory application in Europe and our partner, Genmab, submitted an application in the U.S. for epcoritamab in relapsed/refractory large B-cell lymphoma. We're seeking accelerated approval based on the positive Phase II study results for epcoritamab in this indication, where we saw very deep and durable responses in these highly refractory patients. We expect decisions in both the U.S. and Europe in 2023.

現在轉到我們的腫瘤學產品組合，我們將繼續在我們管道的所有階段取得出色的進展。我們最近在歐洲提交了監管申請，我們的合作夥伴 Genmab 在美國提交了 epcoritamab 治療復發/難治性大 B 細胞淋巴瘤的申請。基於 epcoritamab 在這一適應症中的積極 II 期研究結果，我們正在尋求加速批准，我們在這些高度難治性患者中看到了非常深刻和持久的反應。我們預計 2023 年美國和歐洲都會做出決定。

We are also nearing completion of the registrational studies for 2 additional key programs in our hem/onc portfolio, Venclexta in multiple myeloma and Navitoclax in myelofibrosis. We remain on track to see results from the Phase III CANOVA trial in relapsed/refractory multiple myeloma patients with a t(1114) mutation near the end of this year. Following the event-driven data readout, we anticipate submitting our regulatory applications in the first half of next year.

我們也即將完成 hem/onc 產品組合中另外 2 個關鍵項目的註冊研究，即多發性骨髓瘤中的 Venclexta 和骨髓纖維化中的 Navitoclax。我們仍有望在今年年底前看到針對具有 t(1114) 突變的複發/難治性多發性骨髓瘤患者的 III 期 CANOVA 試驗的結果。在事件驅動的數據讀出之後，我們預計在明年上半年提交我們的監管申請。

For Navitoclax, we remain on track to see data in the first half of next year from both the Phase II REFINE and the Phase III TRANSFORM 1 trials. Results from both studies will be included in our regulatory submissions, which we expect in the second half of 2023.

對於 Navitoclax，我們仍有望在明年上半年看到來自 II 期 REFINE 和 III 期 TRANSFORM 1 試驗的數據。這兩項研究的結果將包含在我們的監管提交中，我們預計在 2023 年下半年提交。

Moving to Neuroscience, where we had applications under active review for several key assets. We anticipate a decision from the FDA in December for Vraylar as an adjunctive treatment for major depressive disorder. We believe Vraylar has the potential to be an important new therapy in this patient population, and we look forward to bringing this new treatment option to patients.

轉向神經科學，我們正在積極審查幾個關鍵資產的申請。我們預計 FDA 會在 12 月做出決定，將 Vraylar 作為重度抑鬱症的輔助治療。我們相信 Vraylar 有可能成為這一患者群體的重要新療法，我們期待為患者帶來這種新的治療選擇。

We also expect a decision from the FDA in the first half of next year for ABBV-951, our innovative subcutaneous levodopa carbidopa delivery system for treatment of advanced Parkinson's disease. And in the area of migraine, we have regulatory applications under review in both the U.S. and Europe for Qulipta as a preventive treatment for patients with chronic migraine, with decisions expected in the first half of next year. 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 making this new oral treatment option available to patients once approved.

我們還預計 FDA 將在明年上半年就 ABBV-951做出決定，這是我們用於治療晚期帕金森病的創新皮下左旋多巴卡比多巴給藥系統。在偏頭痛領域，我們正在美國和歐洲審查 Qulipta 作為慢性偏頭痛患者預防性治療的監管申請，預計將在明年上半年做出決定。如果獲得批准，這將是 Qulipta 的另一個差異化特徵，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，會顯著影響生活質量，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 eye care, our partner, REGENXBIO, recently announced positive interim data from the Phase II [88] dose escalation trial for RGX-314 using in-office [suprachoroidal] delivery for the treatment of wet AMD. RGX-314 continues to be well tolerated with no drug-related serious adverse events and a meaningful reduction in treatment burden was observed at 6 months across all dose levels. Two pivotal trials evaluating RGX-314 for wet AMD using subretinal delivery are active and enrolling patients.

在眼部護理方面，我們的合作夥伴 REGENXBIO 最近公佈了 RGX-314 的 II 期 [88] 劑量遞增試驗的積極中期數據，該試驗使用辦公室 [脈絡膜上] 給藥治療濕性 AMD。 RGX-314 繼續具有良好的耐受性，沒有與藥物相關的嚴重不良事件，並且在所有劑量水平的 6 個月時觀察到治療負擔顯著降低。兩項使用視網膜下給藥評估 RGX-314 治療濕性 AMD 的關鍵試驗正在開展並招募患者。

So in summary, we've continued to make significant progress advancing our programs this year, and we look forward to many more important pipeline milestones in the remainder of this year and into 2023.

總而言之，我們今年繼續在推進我們的計劃方面取得重大進展，我們期待在今年剩餘時間和 2023 年實現更多重要的管道里程碑。

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

有了這個，我將把電話轉給 Rob，就我們第三季度的業績和財務前景發表更多評論。搶？

Thank you, Tom. AbbVie's third quarter results demonstrate the strength of our broad portfolio. The continued robust performance from Skyrizi and Rinvoq are helping offset the impact from higher inflation and the stronger U.S. dollar. We reported adjusted earnings per share of $3.66, which is $0.11 above our guidance midpoint. These results include a $0.02 unfavorable impact from acquired IPR&D expense.

謝謝你，湯姆。艾伯維第三季度的業績證明了我們廣泛的投資組合的實力。 Skyrizi 和 Rinvoq 的持續強勁表現有助於抵消通脹上升和美元走強的影響。我們報告調整後的每股收益為 3.66 美元，比我們的指導中點高 0.11 美元。這些結果包括從獲得的 IPR&D 費用中產生的 0.02 美元的不利影響。

Total net revenues were $14.8 billion, in line with our guidance and up 5.4% on an operational basis, excluding a 2.1% unfavorable impact from foreign exchange.

總淨收入為 148 億美元，符合我們的指引，在運營基礎上增長 5.4%，不包括外匯帶來的 2.1% 的不利影響。

The adjusted operating margin ratio was 53.4% of sales. This includes adjusted gross margin of 85.4% of sales, adjusted R&D investment of 10.8% of sales, acquired IPR&D expense of 0.3% of sales and adjusted SG&A expense of 20.9% of sales. Net interest expense was $497 million, and the adjusted tax rate was 12.9%.

調整後的營業利潤率為銷售額的 53.4%。這包括調整後毛利率佔銷售額的 85.4%、調整後的研發投資佔銷售額的 10.8%、獲得的 IPR&D 費用佔銷售額的 0.3%，調整後的 SG&A 費用佔銷售額的 20.9%。淨利息支出為 4.97 億美元，調整後稅率為 12.9%。

Turning to our financial outlook, we are narrowing our full year adjusted earnings per share guidance to between $13.84 and $13.88. This earnings per share guidance does not include an estimate for acquired IPR&D expense that may be incurred beyond the third quarter. We now expect net revenues of approximately $58.2 billion, reflecting growth of 5.5% on an operational basis. At current rates, we expect foreign exchange to have a 1.9% unfavorable impact on full year sales growth.

談到我們的財務前景，我們將全年調整後每股收益指引縮小至 13.84 美元至 13.88 美元之間。該每股收益指引不包括對可能在第三季度之後發生的已收購 IPR&D 費用的估計。我們現在預計淨收入約為 582 億美元，反映了運營基礎上的 5.5% 的增長。按照目前的匯率，我們預計外匯將對全年銷售增長產生 1.9% 的不利影響。

Included in this guidance are the following updated assumptions. We now expect Skyrizi global sales of approximately $5.1 billion, an increase of $300 million due to strong market share performance. For Venclexta, we now expect global revenue of approximately $2 billion, based on a lower market outlook in CLL and unfavorable foreign exchange. For Aesthetics, we now expect global revenue of approximately $5.3 billion, given the impact of higher inflation on near-term market growth and due to unfavorable foreign exchange.

本指南中包括以下更新的假設。我們現在預計 Skyrizi 的全球銷售額約為 51 億美元，由於市場份額表現強勁，增加了 3 億美元。對於 Venclexta，我們現在預計全球收入約為 20 億美元，基於 CLL 較低的市場前景和不利的外匯。對於美學，我們現在預計全球收入約為 53 億美元，因為通脹上升對近期市場增長的影響以及不利的外匯。

Moving to P&L, we now expect adjusted gross margin of approximately 85% of sales and forecast an adjusted operating margin ratio of approximately 52% of sales. Turning to the fourth quarter, we anticipate net revenues of approximately $15.2 billion. At current rates, we expect foreign exchange to have a 2.5% unfavorable impact on sales growth. We expect adjusted earnings per share between $3.65 and [$3.69]. This guidance does not include acquired IPR&D expense that may be incurred in the quarter.

轉向損益表，我們現在預計調整後的毛利率約為銷售額的 85%，並預測調整後的營業利潤率約為銷售額的 52%。談到第四季度，我們預計淨收入約為 152 億美元。按照目前的匯率，我們預計外匯將對銷售增長產生 2.5% 的不利影響。我們預計調整後的每股收益在 3.65 美元至 [3.69 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 continues to support capital allocation priorities. We generated $17 billion of free cash flow in the first 9 months of the year, and our cash balance at the end of September was $11.8 billion. Underscoring our confidence in AbbVie's long-term outlook, today we announced a 5% increase in our quarterly cash dividend, beginning with the dividend payable in February 2023. And we remain on track to achieve $30 billion of cumulative debt paydown by the end of this year, bringing our net leverage ratio to 1.8x.

最後，艾伯維（AbbVie）強勁的業務表現繼續支持資本配置優先事項。今年前 9 個月，我們產生了 170 億美元的自由現金流，截至 9 月底，我們的現金餘額為 118 億美元。為了強調我們對艾伯維（AbbVie）長期前景的信心，我們今天宣布將季度現金股息增加 5%，從 2023 年 2 月支付的股息開始。我們仍有望在本月底前實現 300 億美元的累計債務償還年，使我們的淨槓桿率達到 1.8 倍。

In closing, AbbVie's strong performance allows us to reaffirm earnings expectations in the face of economic pressure. And with our diverse portfolio, we continue to be well positioned to deliver long-term growth.

最後，艾伯維（AbbVie）的強勁表現使我們能夠在經濟壓力面前重申盈利預期。憑藉我們多樣化的產品組合，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 Liz。

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

謝謝，羅伯。我們現在將打開問題的電話。 （操作員說明）

Operator, we'll take the first question.

接線員，我們將回答第一個問題。

Our first question is from Chris Schott from JPMorgan.

我們的第一個問題來自摩根大通的 Chris Schott。

Just my question is really centered around Humira. And I know you -- appreciate some of the [excess] commentary you made at beginning of the call, but are there any surprises so far in these discussions as we think about where either rebates or prices settling out for Humira? And I'm really just turning my heads around, I think previously, you've commented you expected U.S. Humira erosion to be down roughly 45%, plus or minus 10%. And I just was wondering if that range holds given what you know today about the negotiations?

只是我的問題真的圍繞 Humira。我知道你——感謝你在電話會議開始時發表的一些 [過多] 評論，但到目前為止，當我們考慮到 Humira 的回扣或價格在哪裡結算時，這些討論中是否有任何意外？而且我真的只是轉過頭來，我認為以前，您曾評論過您預計美國修美樂侵蝕將下降約 45%，正負 10%。我只是想知道根據你今天對談判的了解，這個範圍是否成立？

And if I could just do a quick follow up, my second question, Immunology. There was a European JAK update out this morning, and I just was wondering any impact you expect to the Rinvoq franchise for that? Just maybe some context about how relevant, I guess, Europe was as part of the mix? And does that label update kind of impact your outlook at all?

如果我可以快速跟進，我的第二個問題，免疫學。今天早上有一個歐洲 JAK 更新，我只是想知道你對 Rinvoq 特許經營有什麼影響嗎？也許只是一些背景，我猜想，歐洲是其中的一部分？該標籤更新是否會影響您的前景？

Okay, Chris, this is Rick. I'll cover part of that question, and then I'll have Jeff fill in on any additional commentary around the contracting.

好的，克里斯，這是瑞克。我將討論該問題的一部分，然後讓 Jeff 填寫有關合同的任何其他評論。

I think first, if we talk about the 45%, plus or minus 10%, that is the range that we gave. We're obviously working on doing the final forecasting for 2023. As we've said in the past, there are 2 major components which will play into that forecast. One is how are the biosimilars priced, that will certainly have some impact. We won't know that until we actually get into the market and start to see some of that activity.

我認為首先，如果我們談論 45%，正負 10%，這就是我們給出的範圍。我們顯然正在努力對 2023 年進行最終預測。正如我們過去所說，有兩個主要組成部分將影響該預測。一是生物仿製藥如何定價，這肯定會產生一些影響。在我們真正進入市場並開始看到其中的一些活動之前，我們不會知道這一點。

But the other big component is obviously our coverage, our access coverage for Humira and the position that Humira has on those formularies. I would say that negotiating by Jeff's team is going very well. As I mentioned in my comments, we're at about 80% of all covered lives now, and I would expect that to rise to a level that's above 90% as we move towards the end of the year. Once we have a final number there, it will allow us to do the final modeling for 2023, and that's at the point where we'll be able to refine that 45% plus or minus 10%.

但另一個重要組成部分顯然是我們的覆蓋範圍，我們對 Humira 的訪問覆蓋範圍以及 Humira 在這些處方集上的位置。我會說 Jeff 團隊的談判進展順利。正如我在評論中提到的那樣，我們現在約佔所有受保人的 80%，我預計隨著我們接近年底，這一比例將上升到 90% 以上。一旦我們有了最終數字，它將允許我們為 2023 年進行最終建模，屆時我們將能夠改進 45% 正負 10%。

I'd tell you it's going on track. I would say there's no surprises, and I'd say I feel good about how the negotiations are going with all the major managed care organizations and PBMs.

我會告訴你它正在走上正軌。我會說沒有任何意外，我會說我對與所有主要管理式醫療組織和 PBM 的談判進展感到滿意。

Jeff, anything you'd add there?

傑夫，你有什麼要補充的嗎？

No. Just to confirm, Rick, that no real surprises in terms of where we've been. And as we've communicated before, our principles of co-existing over time with one or more biosimilars seems to be the way that the market will play out. And certainly, like we saw in Europe that we had the principle of -- for patient continuity to concede pricing to maintain that patient access. So Chris, no major surprises that we've seen so far.

不，只是為了確認，瑞克，就我們去過的地方而言，沒有真正的驚喜。正如我們之前所傳達的，隨著時間的推移，我們與一種或多種生物仿製藥共存的原則似乎是市場發展的方式。當然，就像我們在歐洲看到的那樣，我們的原則是——為了患者的連續性，讓定價以維持患者的訪問。所以克里斯，到目前為止，我們沒有看到任何重大驚喜。

And then do you want to talk about PRAC? Roopal, if you're going to talk about PRAC.

然後你想談談PRAC嗎？ Roopal，如果您要談論 PRAC。

Maybe, Roopal, you could address the procedure and where we are in the procedure, and I'll cover the commercial.

也許，Roopal，你可以解決程序以及我們在程序中的位置，我將介紹廣告。

Yes. Thanks, Jeff. I'll give some context. So the next step here after PRAC would be moving to the CHMP here in November, and then the European Commission should finalize this. We expect December or January.

是的。謝謝，傑夫。我會給出一些背景信息。因此，PRAC 之後的下一步將是在 11 月轉移到這裡的 CHMP，然後歐盟委員會應該最終確定這一點。我們預計 12 月或 1 月。

So PRAC completed their review, and what we see in the labeling is an update in warnings, and this is related to outcomes of the oral surveillance study. And in particular, in Section 4.4, which is the warnings, there's a list of subgroups that were found to be at risk based on analysis from oral surveillance. For example, patients greater than or equal to the age of 65, those that are at risk for cardiac events, smokers, for example. And in these patients, the use of JAK inhibitors would be after a consideration of other therapies, if I'm paraphrasing, if no suitable alternatives.

所以 PRAC 完成了他們的審查，我們在標籤中看到的是警告的更新，這與口腔監測研究的結果有關。特別是，在第 4.4 節中，即警告中，有一個根據口頭監測分析發現有風險的亞組列表。例如，大於或等於 65 歲的患者、有心臟事件風險的患者、吸煙者等。在這些患者中，如果沒有合適的替代方案，JAK 抑製劑的使用將在考慮其他療法之後進行。

So this is consistent with the practice of medicine. It provides specific guidance, and we would say pragmatic at this stage.

所以這與醫學實踐是一致的。它提供了具體的指導，在這個階段我們會說是務實的。

And Chris, to that point, I mean, this is largely consistent with what we see from oral surveillance and the (inaudible) label, which is widely sort of understood by the European physicians. And so to cut to the quick, we don't anticipate a material impact as this continues through the process.

克里斯，就這一點而言，我的意思是，這在很大程度上與我們從口腔監測和（聽不清）標籤中看到的一致，這是歐洲醫生廣泛理解的。因此，為了快速切入，我們預計不會產生實質性影響，因為這會在整個過程中繼續進行。

Thanks, Chris.

謝謝，克里斯。

Our next question is from Tim Anderson from Wolfe Research.

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

I was under the impression that we get more granularity on Humira erosion this quarter, and you're saying that's really going to come in Q4. So I'm wondering did I kind of not hear it right before, or has something changed?

我的印像是我們在本季度對 Humira 侵蝕有更多的了解，你說這真的會在第四季度出現。所以我想知道我之前是不是沒聽過，還是有什麼變化？

And then second question is just on contracting in general, my understanding is that payer contracts they're really not rock solid. They can be reopened when there's a change in the marketplace on things like pricing, in this case of biosimilars. So when we do kind of get whatever next level of guidance we get from you, isn't that going to continue to remain fluid? Because market dynamics won't all play out as of January. We'll get to mid next year, you'll get more entrants, you'll know pricing better and that sort of thing?

然後第二個問題只是關於一般合同，我的理解是付款人合同他們真的不是堅如磐石。當市場在定價等方面發生變化時，它們可以重新開放，在這種情況下是生物仿製藥。因此，當我們確實從您那裡獲得任何下一級的指導時，那不是會繼續保持流動嗎？因為市場動態不會在 1 月份全部顯現。我們會到明年年中，你會得到更多的參賽者，你會更好地了解定價等等？

Yes, Tim, this is Rick. I'll cover that one. So I think we've talked a number of times on these calls about what we project in the third quarter call, and I believe what we said is that we would ultimately provide you an update on where we were in the process. And so that's what we attempted to do. I can't give you a number for 2023 until I know what the total access is, and not all those contracts are done yet. They're proceeding well, so I feel good about that. But until we actually know that the contract is solid and we know what that access looks like, we can't give you an accurate projection.

是的，蒂姆，這是瑞克。我會覆蓋那個。因此，我認為我們已經在這些電話會議上多次討論了我們在第三季度電話會議中的計劃，我相信我們所說的是我們最終會向您提供我們在此過程中的最新情況。這就是我們試圖做的。在我知道總訪問量是多少之前，我不能給你一個 2023 年的數字，而且還沒有完成所有這些合同。他們進展順利，所以我對此感覺很好。但在我們真正知道合同是可靠的並且我們知道訪問是什麼樣子之前，我們無法給你一個準確的預測。

And I understand the desire by the investment community. I understand what that number is, but I think you probably also understand that we want to give you the most accurate number that we can give you, and we don't want to give you a number that's not accurate. And so it is going to require us until we get to the fourth quarter call to provide that for you.

我理解投資界的願望。我知道這個數字是什麼，但我想你可能也明白我們想給你我們能給你的最準確的數字，我們不想給你一個不准確的數字。因此，在我們接到第四季度電話會議之前，我們需要為您提供這些信息。

You are correct, in a sense, about the way you describe how these contracts work. They can be reopened at some point in time. I wouldn't say that's all that common. Usually, and in particular, I'd say, around this kind of a situation, you're going to anticipate what you think is going to happen in the second half of the year and try to position the contract in a way that it can ultimately deal with those changes going forward. But you are correct to say that they could reopen a contract if they chose to do that. There are various kinds of contracts that we use. In some cases, there are penalties or repercussions that would have to come into consideration if a contract got reopened at some point in time. They're not all like that, but many are like that. So it varies. And I'd say, generally speaking, your concept is valid.

從某種意義上說，您描述這些合同如何運作的方式是正確的。它們可以在某個時間點重新打開。我不會說這很常見。通常，特別是，我會說，在這種情況下，你會預測你認為下半年會發生什麼，並嘗試以一種可以的方式定位合同最終應對未來的這些變化。但是你說他們可以重新簽訂合同，如果他們選擇這樣做是正確的。我們使用各種類型的合約。在某些情況下，如果合同在某個時間點重新開放，則必須考慮到處罰或影響。他們不都是這樣，但很多人都是這樣。所以它會有所不同。我想說，一般來說，你的概念是有效的。

But I would say it's probably a little less fluid than the way you necessarily described it, particularly in this environment where we know there will be a number of biosimilars coming in. So we anticipate that we've built the contracts around that set of assumptions.

但我會說它可能比你所描述的方式不太流暢，特別是在我們知道會有許多生物仿製藥進入的環境中。所以我們預計我們已經圍繞這組假設建立了合同.

Jeff, anything you'd add?

傑夫，你有什麼要補充的嗎？

I think, Tim, Rick described it in the right way. While there are typically -- they're typically out clauses based on timing or other dynamics, I think one of the considerations is obviously, as we've highlighted before, most of the biosimilars are going to be coming in the second half of the year. So to some degree, that actually limits if it was a rare case. And they typically are rare where a contract is blown up or renegotiated in the middle of the year, that length of time that's left in '23 for some of those payers to -- let's take a negative action, put some natural constraint on them in terms of when they would time that out. But Rick highlighted it very nicely in terms of the dynamics.

我認為，蒂姆，瑞克以正確的方式描述了它。雖然通常有 - 它們通常是基於時間或其他動態的條款，但我認為其中一個考慮因素顯然是，正如我們之前強調的那樣，大多數生物仿製藥將在下半年上市年。所以在某種程度上，這實際上限制了它是否是罕見的情況。在年中合同被取消或重新談判的情況下，它們通常很少見，在 23 年留給一些付款人的時間長度 - 讓我們採取負面行動，對他們施加一些自然約束他們何時會超時的條款。但里克在動態方面很好地強調了它。

Thanks, Tim.

謝謝，蒂姆。

Our next question comes from Mohit Bansal from Wells Fargo.

我們的下一個問題來自富國銀行的 Mohit Bansal。

And maybe one more question on the contracting side. Could you help us understand if the pricing part of the contracts is something that you have a good handle on at this point? And then a follow-up question is that how do you think about the cadence of BD activity once you hit the mark of less than 2x leverage by end of the year?

也許還有一個關於承包方的問題。您能否幫助我們了解合同的定價部分是否是您目前可以很好處理的事情？然後一個後續問題是，一旦您在年底達到低於 2 倍的槓桿率，您如何看待 BD 活動的節奏？

Jeff, do you want to cover that?

傑夫，你想報導嗎？

Yes. So look, in terms of what Rick had highlighted in terms of our confidence in projecting the 80%, obviously, there's a couple of components to that. So we have -- while all the contracts aren't fully complete, with the ones that we've done, we've done some significant modeling work to understand if we're retaining the ability to stay on the formulary, we would model our volume. Like how much would we retain versus would go to one or more biosimilars, that's something that we can understand. And we have made base case, both first half and second half pricing assumptions based on those contracts.

是的。所以看，就 Rick 強調的我們對預測 80% 的信心而言，顯然有幾個組成部分。所以我們有 - 雖然所有合同都沒有完全完成，但我們已經完成了一些重要的建模工作，以了解我們是否保留留在處方集中的能力，我們會建模我們的音量。就像我們會保留多少與會使用一種或多種生物仿製藥一樣，這是我們可以理解的。我們已經根據這些合同做出了上半年和下半年的定價假設。

Now, what's been highlighted in the last couple of questions is there's still uncertainty on the rest of the contracts that are yet to have been secured and also a bit on that second half price dynamic. So those are the elements that are going to give us more confidence as we go to the fourth quarter call to give everyone a secure number for next year.

現在，在最後幾個問題中強調的是，其餘尚未獲得的合同仍然存在不確定性，下半年價格動態也存在一些不確定性。因此，當我們進行第四季度電話會議時，這些因素將使我們更有信心，以便為每個人提供明年的安全號碼。

This is Rick. I'll cover your business development question. I think if I step back and I look at where are we today, we have been over the last several years, operating with an approach of roughly $2 billion to add incremental pieces to the business. We've effectively used that over the last several years to be able to build some additional, particularly, I'd say, early stage pipeline [assets] to the company. We're continuing on that same approach right now.

這是瑞克。我將介紹您的業務發展問題。我想，如果我退後一步，看看我們今天在哪裡，我們在過去幾年中一直在以大約 20 億美元的方式運營，以增加業務的增量。在過去的幾年裡，我們有效地利用了這一點，能夠為公司建立一些額外的，特別是我想說的早期管道 [資產]。我們現在繼續採用同樣的方法。

Now having said that, we obviously have paid down debt very rapidly. We will be in a position where if we chose to do something, we could do something. I'd say if I look at the business today and I look at how it's performing around the expectations that we had for the business going forward, I would say there's no need for us to be able to do anything in that area.

話雖如此，我們顯然已經非常迅速地償還了債務。我們將處於如果我們選擇做某事，我們就可以做某事的位置。我想說，如果我今天看一下業務，看看它是如何圍繞我們對未來業務的期望進行的，我會說我們沒有必要在該領域做任何事情。

And I go back to the original premise of what we described to the investment community on what we believe would happen when biosimilars entered the U.S. market for Humira. What we said was that we believe the bulk of the erosion would occur in 2023, some additional erosion in 2024, and '25 and beyond, we would return to significant growth. We'd be able to deliver high single-digit growth from that point forward to the end of the decade. That's what we said. Everything I know about the business today would suggest to me that we are able to do just that, and we're confident that we're able to do that with the portfolio we have, and the late-stage pipeline and additional indications that we have coming forward.

我回到我們向投資界描述的最初前提，即我們認為當 Humira 的生物仿製藥進入美國市場時會發生什麼。我們所說的是，我們相信大部分侵蝕將發生在 2023 年，一些額外的侵蝕將在 2024 年發生，到 25 年及以後，我們將恢復顯著增長。從那時到本世紀末，我們將能夠實現高個位數的增長。這就是我們所說的。我今天對業務的了解都會向我表明我們能夠做到這一點，我們相信我們能夠通過我們擁有的投資組合、後期管道和其他跡象表明我們能夠做到這一點已經挺身而出。

Having said that, I can also tell you that over the last 10 years, we've demonstrated to ourselves and hopefully to you that we can acquire businesses and assets, and we can integrate those and we can successfully drive those. And so if we found something that we thought was very important to add to the business, we certainly had the financial wherewithal and this business has tremendous cash flow, we could do that. I can tell you we don't see that right now, so I wouldn't assume that.

話雖如此，我還可以告訴你，在過去的 10 年裡，我們已經向自己證明了，並希望向你證明我們可以收購業務和資產，我們可以整合這些，我們可以成功地推動這些。因此，如果我們發現一些我們認為對業務非常重要的東西，我們當然有財力，而且這項業務有巨大的現金流，我們可以做到。我可以告訴你，我們現在看不到這一點，所以我不會假設。

And the other thing I'd point out is, as an example, the most important thing -- I know everyone is focused on what that erosion curve is going to look like, including us, to be honest, but -- and I know why. But probably the single most important thing for us going forward to hit what I described to you a moment ago is that underlying non-Humira business growing at a rate that can drive those expectations, and that's key.

我要指出的另一件事是，作為一個例子，最重要的事情——老實說，我知道每個人都關注侵蝕曲線的樣子，包括我們在內，但是——我知道為什麼。但對我們來說，實現我剛才向您描述的最重要的事情可能是潛在的非修美樂業務以可以推動這些期望的速度增長，這是關鍵。

And I'd say there's 2 factors that are most important around that. The first is that Skyrizi and Rinvoq grow fast enough that they can more than offset, that they can essentially grow through all of the erosion that occurs on Humira and deliver incremental performance above and beyond that, and we feel highly confident in that. I mean, when you can look at the trajectories of those assets now, in the early phase we're in right now in IBD and PSA, I would say I have a very high level of confidence that they will perform at that level or well above that level.

我想說有兩個最重要的因素。首先是 Skyrizi 和 Rinvoq 增長得足夠快，足以抵消它們的影響，它們基本上可以通過 Humira 上發生的所有侵蝕而增長，並提供超出此範圍的增量性能，我們對此充滿信心。我的意思是，當您現在可以查看這些資產的軌跡時，在我們現在處於 IBD 和 PSA 的早期階段時，我會說我非常有信心他們將在那個水平或良好表現高於那個水平。

Then the second thing is all the other growth assets. They have to be growing fast enough that they can get us to be able to grow at that rate that I described. And if you take this quarter as an example, and you look at the business without Humira, the underlying growth is about 6.5%. And remember, that 6.5% is absorbing the economic impact we see in the Aesthetics business and the market and competitive dynamics that we see in Imbruvica, so that tells you that underlying growth is pretty strong.

其次是所有其他增長資產。它們必須增長得足夠快，才能使我們能夠以我所描述的速度增長。如果以本季度為例，看看沒有修美樂的業務，潛在增長率約為 6.5%。請記住，這 6.5% 正在吸收我們在美學業務中看到的經濟影響以及我們在 Imbruvica 看到的市場和競爭動態，因此這告訴您潛在的增長非常強勁。

And so I think those are the important things that investors have to focus on, and the erosion curve is certainly one of those. And I'm sensitive to the fact that you want to know when you're going to hit trough earnings, I recognize that, and that's why we wanted to provide you some assurance of what that trough earnings is going to look like.

所以我認為這些是投資者必須關注的重要事情，侵蝕曲線肯定是其中之一。而且我很敏感，你想知道你什麼時候會觸及低谷收益，我認識到這一點，這就是為什麼我們想為你提供一些關於低谷收益會是什麼樣子的保證。

Thanks, Mohit.

謝謝，莫希特。

Our next question comes from Terence Flynn from Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Terence Flynn。

Maybe 2 for me. Rick, I appreciate your comments on 2023 and the Aesthetics business. I know you don't want to give guidance. But I guess, at a high level, do you think you can grow that franchise next year versus this year?

對我來說可能是 2 個。里克，感謝您對 2023 年和美學業務的評論。我知道你不想提供指導。但我想，在較高的水平上，你認為明年與今年相比，你能增加球隊的實力嗎？

And then on epcoritamab, congratulations on the filing there. Just wondering what you're expecting regarding the requirement for inpatient administration? J&J recently got approval of their bispecific in myeloma, and it looks like there's a requirement there for inpatient administration of the drug during step-up period. So just wondering how we should think about inpatient versus outpatient dosing of epco?

然後在 epcoritamab 上，祝賀那裡的文件。只是想知道您對住院管理的要求有何期望？強生最近獲得了他們在骨髓瘤中的雙特異性藥物的批准，看起來在升壓期間需要住院給藥。所以只是想知道我們應該如何考慮 epco 的住院和門診劑量？

Okay. Thanks, Terence. I'll cover the first one. So if I look at the Aesthetics business, we're clearly seeing this economic pressure in the U.S., and I would expect that we will see that to continue into 2023. Certainly, it's difficult to predict what will happen in the U.S.? Will it get worse? Will we go into a recession? Will it stay about the same? I'd say we're looking at this extremely carefully.

好的。謝謝，特倫斯。我將介紹第一個。因此，如果我看一下美學業務，我們清楚地看到了美國的這種經濟壓力，我預計這種壓力將持續到 2023 年。當然，很難預測美國會發生什麼？會變得更糟嗎？我們會陷入衰退嗎？它會保持不變嗎？我會說我們正在非常仔細地看待這個問題。

The good news right now, I would say, is that the factors that we're looking at that seem to be driving this consumer confidence and behavior the most in the U.S. appear to have stabilized at the levels that they're at, and so I would say that's a positive thing. Now it's fluid because obviously, if the economic situation got worse in the U.S., my guess is they would trend down again. And so -- but at least it appears right now that they've stabilized and maybe even ticked up just a little bit, meaning moved in a positive direction just a little bit. I think it's very difficult to predict.

我想說的是，現在的好消息是，我們正在研究的那些似乎推動美國消費者信心和行為最多的因素似乎已經穩定在他們所處的水平，所以我會說這是一件積極的事情。現在它是流動的，因為顯然，如果美國的經濟形勢惡化，我的猜測是它們會再次呈下降趨勢。所以——但至少現在看來，它們已經穩定下來，甚至可能只是一點點上升，這意味著向積極的方向移動了一點點。我認為很難預測。

Here's what I would assume. I would assume that a significant part of '23, we will have an impact on it. Now I also recognize that we saw this phenomenon, as we said in the last call, start in May. We weren't sure at that time whether it was the summer season starting a month early or it was the economic impact, because we have been watching the indicators and they trend down several months ahead of that, but we didn't see an impact until the month of May. So the point is, when we hit May and beyond, we're going to be lapping the impact, so the negative impact will be softened on the business. So we'll return to better growth rates no matter what just mathematically, right?

這就是我的假設。我會假設 23 年的一個重要部分，我們將對它產生影響。現在我也認識到我們看到了這種現象，正如我們在上次電話會議中所說，從 5 月開始。當時我們不確定是提前一個月開始的夏季還是經濟影響，因為我們一直在觀察指標，並且在此之前幾個月它們呈下降趨勢，但我們沒有看到影響直到五月。所以關鍵是，當我們在 5 月及以後，我們將受到影響，因此對業務的負面影響將會減弱。因此，無論在數學上如何，我們都會恢復到更好的增長率，對吧？

So -- but I think the best prediction we can have is it's going to have an impact in a good part of '23. I think is the best way for us to think about it. Again, the rest of the business has an opportunity to be able to offset that as we saw in this quarter.

所以——但我認為我們能做的最好的預測是它將在 23 年的大部分時間裡產生影響。我認為這是我們思考它的最佳方式。同樣，正如我們在本季度看到的那樣，其他業務有機會能夠抵消這一點。

And this is Rob. I would just add that if you think about more long term, if you think about what happened in '08 and '09, the business declined high single digits. And then we saw, after that, very robust growth in the mid-teens in the next decade. So given that penetration rates are still very low today, there's clearly ample opportunity to grow this market. I think once you get on the other side of the economic impact which we expect to be transient, we still expect there's a long-term growth. As Rick highlighted earlier, we're still on track for that long-term high single-digit growth getting to greater than $9 billion by 2029. So we'll have to navigate obviously the short-term economic impact, but we still have tremendous confidence in the long-term outlook for Aesthetics.

這是羅伯。我只想補充一點，如果您考慮更長期的情況，如果您考慮 08 和 09 年發生的事情，該業務下降了高個位數。然後我們看到，在那之後，未來十年中青少年的增長非常強勁。因此，鑑於今天的滲透率仍然很低，顯然有足夠的機會來發展這個市場。我認為，一旦您擺脫了我們預計是短暫的經濟影響，我們仍然預計會有長期增長。正如 Rick 早些時候強調的那樣，我們仍有望實現到 2029 年超過 90 億美元的長期高個位數增長。因此，我們顯然必須應對短期經濟影響，但我們仍然擁有巨大的對美學的長期前景充滿信心。

This is Neil Gallagher, I'll take the epco question. So the first thing, I just want to caution -- a word of caution before I answer your question directly around inpatient stay, which is with the patient population that our competitor studied with the BCMA-CD3 is quite different in terms of overall benefit risk. So the indication that was granted was in fifth line plus multiple myeloma, which is a very heavily pre-treated and frail population. So to extrapolate any interpretation of benefit risk from that population into the relapsed/refractory DLBCL population that we have studied and filed for with epcoritamab would not be valid. So just a word of caution there.

我是 Neil Gallagher，我會回答 epco 的問題。因此，首先，我想提醒一下——在我直接回答您關於住院時間的問題之前，請注意，我們的競爭對手使用 BCMA-CD3 研究的患者群體在總體收益風險方面完全不同.因此，被授予的適應症是五線加多發性骨髓瘤，這是一個經過大量預處理和虛弱的人群。因此，將對該人群的受益風險的任何解釋外推到我們研究並提交給 epcoritamab 的複發/難治性 DLBCL 人群中是無效的。因此，請注意。

That said, the study that we filed had requirement for 24 hour patients stay, one overnight stay. However, in subsequent studies, we are aiming to remove that requirement, so patients would not require -- be required to remain overnight. And we do believe because of the emergent and stable overall benefit risk for epcoritamab, a couple of things that we believe that it has potential to be best-in-class. We also believe that our strategy to remove overnight stays is a very valid one and reasonable one to pursue. Hope that answers your question.

也就是說，我們提交的研究要求患者留院 24 小時，留宿一晚。然而，在隨後的研究中，我們的目標是取消這一要求，因此患者不需要——被要求過夜。而且我們確實相信，由於 epcoritamab 的新興且穩定的整體收益風險，我們認為它有可能成為同類最佳的幾件事。我們還認為，我們取消過夜住宿的策略是一個非常有效且合理的策略。希望這能回答你的問題。

Thanks, Terence.

謝謝，特倫斯。

Our next question is from Andrew Baum from Citigroup Global.

我們的下一個問題來自 Citigroup Global 的 Andrew Baum。

A couple of questions, please. First, on Imbruvica. I'm assuming that Imbruvica is going to be included in the top 10 CMS list for price negotiation under Medicare next year. Assuming that's correct, what do you think about the impact on net pricing for Imbruvica? Do you anticipate pricing, net pricing coming under pressure prior to 2026, given the contracting that's expecting to take place among your competitors to secure formulary positions given the catastrophic coverage burden on PBM post the IRA implementation? So is the impact kind of go forward for the class, including for Imbruvica before you actually get the price cut coming?

有幾個問題，請。首先，關於因布魯維卡。我假設 Imbruvica 將被列入明年醫療保險價格談判的前 10 名 CMS 名單。假設這是正確的，您如何看待 Imbruvica 對淨定價的影響？鑑於 IRA 實施後 PBM 的災難性覆蓋負擔，您是否預計 2026 年之前定價和淨定價將面臨壓力？那麼，在你真正降價之前，包括對 Imbruvica 在內的課程的影響是否會繼續？

And then second, with epcoritamab, there's been some interesting data on the importance of profound B-cell depletion in lupus, using CAR-T assets. As CD20 bispecific could get to a similar level, I'm wondering whether you have interest in pivoting epcoritamab and exploring it in refractory lupus, as one of your competitors already is, particularly given you have a subcu administration, which obviously has some advantages?

其次，對於 epcoritamab，有一些有趣的數據表明使用 CAR-T 資產在狼瘡中深度 B 細胞耗竭的重要性。由於 CD20 雙特異性可能達到相似的水平，我想知道您是否有興趣將 epcoritamab 轉向並在難治性狼瘡中探索它，因為您的競爭對手之一已經是，特別是考慮到您有一個 subcu 管理，這顯然有一些優勢？

Andrew, it's Jeff. I'll take your first question. So when we -- obviously, we're still studying very carefully the IRA. And we're also discussing directly with CMS, not just through pharma, but our own company in terms of how they're going to basically select the different drugs that will be negotiated. And that's a little bit unclear at this point. It's not unreasonable based on the size of Imbruvica to suspect it will be one of the earlier drugs that could potentially be negotiated. So just to clear that.

安德魯，我是傑夫。我會回答你的第一個問題。因此，當我們——顯然，我們仍在非常仔細地研究 IRA。我們還直接與 CMS 進行討論，不僅通過製藥公司，還通過我們自己的公司討論他們將如何基本上選擇將要談判的不同藥物。在這一點上，這有點不清楚。根據 Imbruvica 的規模，懷疑它將成為可能談判的早期藥物之一併非不合理。所以只是為了清除這一點。

In terms of what may take place before that potential negotiation in 2026, I would expect to see some modest changes in rebating. We see very small levels at this point now, but we do have a third competitor coming so that would be something that we would continue to plan for as we move into that potential event.

就 2026 年潛在談判之前可能發生的情況而言，我預計回扣會出現一些適度的變化。我們現在看到的水平非常低，但我們確實有第三個競爭對手來，所以這將是我們在進入那個潛在事件時繼續計劃的事情。

And this is Tom, maybe I'll answer the lupus question. First, I'll say it's actually -- it was very exciting to see that paper showing that B-cell depletion can actually put patients with very severe lupus in remission. It's a very small study, it's some 5 patients, but everyone is looking at this as -- even with a surprise, because we used to think we had to affect many mechanisms themselves in lupus, so that was one of the reasons it's so difficult. I used to be part of a lupus clinic in Montreal, so I know the challenges with patients.

這是湯姆，也許我會回答狼瘡問題。首先，我要說的是——看到那篇論文表明 B 細胞耗竭實際上可以使非常嚴重的狼瘡患者得到緩解，這非常令人興奮。這是一項非常小的研究，大約有 5 名患者，但每個人都將其視為 - 即使感到驚訝，因為我們曾經認為我們必須影響狼瘡的許多機制，所以這就是它如此困難的原因之一.我曾經是蒙特利爾狼瘡診所的一員，所以我知道患者面臨的挑戰。

So what we're looking at right now is we're asking -- yes, the answer to your question is, can we use our existing assets and collaborations to see if we can do B-cell depletion for -- as a treatment for lupus. The answer is yes. And the type of questions we're asking ourselves is do we have to have as deep a depletion as we have with in [heme] malignancies. Nobody knows the answer. That might be important because if you have to have a very deep depletion, it might be restricted more to more of the severe patients, and again, that would be an advantage. But if we want to go to all lupus patients, because not all lupus patients are flaring all the time. The majority have a normal life, they go to a clinic once a year and just see their physicians when they have flares. So going to a very deep regimen for B-cell depletion might be deemed too severe.

所以我們現在正在研究的是我們在問 - 是的，你的問題的答案是，我們可以使用我們現有的資產和合作來看看我們是否可以做 B 細胞消耗 - 作為治療狼瘡。答案是肯定的。我們要問自己的問題類型是，我們是否必須像在 [血紅素] 惡性腫瘤中那樣深度消耗。沒有人知道答案。這可能很重要，因為如果您必須進行非常深的消耗，它可能會更多地限制在更多的重症患者身上，這將是一個優勢。但如果我們想看所有狼瘡患者，因為並非所有狼瘡患者都一直在發作。大多數人過著正常的生活，他們每年去一次診所，只是在發作時去看醫生。因此，對 B 細胞耗竭進行非常深入的治療可能被認為過於嚴重。

So the question is, yes, we're looking at it and trying to figure out what's the right regimen and how do we approach that in lupus is very exciting questions, which we're obviously looking into.

所以問題是，是的，我們正在研究它並試圖找出正確的治療方案以及我們如何在狼瘡中解決這個問題，這是非常令人興奮的問題，我們顯然正在研究。

Thanks, Andrew.

謝謝，安德魯。

Our next question comes from Steve Scala from Cowen.

我們的下一個問題來自 Cowen 的 Steve Scala。

What is your level of confidence in a positive outcome for Vraylar in MDD at the end of the year? I imagine the review is well along, so you probably have good visibility. So for instance, are labeling discussions underway? Is the sales force being trained, et cetera? This is a very large opportunity that does not seem to be a point of external focus as far as I can tell, so I'm wondering what you could tell us about how things are going.

您對 Vraylar 在今年年底在 MDD 中取得積極成果的信心程度如何？我想審查進展順利，所以你可能有很好的知名度。例如，是否正在進行標籤討論？銷售人員是否正在接受培訓等？這是一個非常大的機會，據我所知，這似乎不是外部關注點，所以我想知道你能告訴我們事情的進展情況。

Roopal?

羅帕爾？

It's Roopal, thanks for the question. Maybe I'll go, and then Jeff can talk about the opportunity.

我是 Roopal，謝謝你的提問。也許我會去，然後傑夫可以談談這個機會。

You're correct. The review is proceeding per our expectations. We have 2 positive studies in this space. We -- I mean, we recall we also have the same endpoint, the depression endpoint that's read out in 3 other bipolar depression studies that are already within label. So there's quite a bit of evidence that's already been generated that's in front of the agency now. So I would say it's proceeding well, and we still anticipate a decision by year-end.

你是對的。審查正在按照我們的預期進行。我們在這個領域有 2 項積極的研究。我們——我的意思是，我們記得我們也有相同的終點，即在其他 3 項已經在標籤內的雙相抑鬱症研究中讀出的抑鬱終點。所以有相當多的證據已經產生，現在擺在該機構面前。所以我會說它進展順利，我們仍然期待在年底前做出決定。

And I'll pass it to Jeff.

我會把它交給傑夫。

Yes. Steve, and just in terms of your sales force question, I mean, we are very encouraged and excited about this potential approval. I mean, obviously, we continue to gain share week by week sequentially for our base indication, the bipolar indications. And we know that based on the profile that we have with Vraylar, so very, very strong efficacy, proven efficacy of a very good tolerability profile for an antipsychotic. No material weight gain, low metabolic effects. And I think importantly, and maybe not as appreciated, so it's -- there's no titration. You have a very simple starting dose of 1.5 milligrams.

是的。史蒂夫，就您的銷售人員問題而言，我的意思是，我們對這種潛在的批准感到非常鼓舞和興奮。我的意思是，顯然，對於我們的基本指標，雙極指標，我們繼續逐週獲得份額。而且我們知道，根據我們對 Vraylar 的描述，非常非常強的功效，證明了抗精神病藥具有非常好的耐受性特徵的功效。無物質增重，代謝影響低。而且我認為重要的是，也許沒有那麼受歡迎，所以它 - 沒有滴定。您的起始劑量非常簡單，為 1.5 毫克。

So as we do our research, we see that that profile is very strong as this potential add-on therapy in depression. In the last decade, there's been only one drug that's been approved for this indication, and that's Rexulti. And we think -- that's a branded drug, obviously, and we think we can compete very, very well. So we have a big existing sales force and infrastructure, we are gearing up in terms of training, we have the established relationships across the big primary care doctors as well as the psychiatrists. So we are -- we agree with your approach that a meaningful commercial opportunity that could evolve very quickly here once we get the approval.

因此，當我們進行研究時，我們發現這種情況非常強大，因為這種潛在的抑鬱症附加療法。在過去的十年裡，只有一種藥物被批准用於這種適應症，那就是 Rexulti。我們認為 - 顯然，這是一種品牌藥物，我們認為我們可以非常非常好地競爭。因此，我們擁有龐大的現有銷售隊伍和基礎設施，我們正在為培訓做準備，我們在大型初級保健醫生和精神科醫生之間建立了關係。因此，我們同意您的方法，即一旦我們獲得批准，這是一個有意義的商業機會，可以在這裡迅速發展。

Thanks, Steve.

謝謝，史蒂夫。

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

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

First, could you just provide some more color on how much of a benefit you're seeing for Skyrizi and Rinvoq in IBD as you've been spending more time with the GIs? And have your outlooks changed on the potential there as major contributors to the long-term growth for those franchises? So where are both of those being used in the treatment paradigms for the respective indications, in Crohn's and ulcerative colitis? So that's one.

首先，您能否提供更多關於您在 IBD 中為 Skyrizi 和 Rinvoq 看到的好處的更多顏色，因為您在 GI 上花費了更多時間？您對那裡作為這些特許經營權長期增長的主要貢獻者的潛力的看法是否發生了變化？那麼，在克羅恩病和潰瘍性結腸炎的治療範式中，這兩種方法都在哪裡使用呢？所以這是一個。

And then secondly, just OpEx came in much lower than we expected, so you seem to be getting better operating leverage than what you originally guided. Are there areas where you've scaled back in spending, whether in Aesthetics or hem/onc, if there's pressures there? And how will you be thinking about that into the Humira LOE next year? So how much additional flexibility might you have on the spending side?

其次，只是運營支出比我們預期的要低得多，因此您似乎獲得了比您最初指導的更好的運營槓桿。如果有壓力，您是否在某些領域縮減了支出，無論是在美學還是下擺/onc 方面？您將如何考慮明年的 Humira LOE？那麼，您在支出方面還有多少額外的靈活性？

Jeff?

傑夫?

Yes, I'll take the IBD question. I think we've mentioned before that the IBD has been a very important part of our long-range plan. And when we gave the 2025 guidance, it looks relatively small because they're just ramping now.

是的，我會回答 IBD 的問題。我想我們之前已經提到過，IBD 一直是我們長期計劃中非常重要的一部分。當我們給出 2025 年的指導時，它看起來相對較小，因為它們現在只是在增加。

I would say that as AbbVie, we are very, very encouraged, as I mentioned in my prepared remarks, on the launch. And maybe I'll start with what we're hearing from the gastroenterologists. I think first is they look at both assets and the global guidelines, the impressions and the clinical approach that we hear from the top leaders and also the community gastros is this idea over I have to start to think about endoscopic healing. Higher, basically, rates of efficacy and more significant clarity on what it's doing in the bowel versus just symptoms. And that seems straightforward, but we see the market moving very, very fast there in terms of understanding. And that's what we can deliver, whether it's the Skyrizi data on the endoscopic healing rates with a very, very convenient and strong safety profile or similar on the Rinvoq side in second line -- in the U.S., second line for patients that aren't doing well in UC.

我想說，作為艾伯維，正如我在準備好的講話中提到的那樣，我們對此次發布感到非常非常鼓舞。也許我會從我們從胃腸病學家那裡聽到的內容開始。我認為首先是他們著眼於資產和全球指導方針，我們從高層領導和社區胃病中聽到的印象和臨床方法是這個想法，我必須開始考慮內窺鏡治療。基本上，更高的功效率和更清楚地說明它在腸道中的作用與僅症狀相比。這似乎很簡單，但我們看到市場在理解方面的發展非常非常快。這就是我們可以提供的，無論是關於內窺鏡癒合率的 Skyrizi 數據，具有非常、非常方便和強大的安全性，或者在 Rinvoq 方面的二線 - 在美國，二線患者不是在UC表現不錯。

So we see rapid adoption already. As I mentioned that in the Rinvoq in the United States will be a second line plus based on the label, and we see very, very fast adoption. I'll give you some color on it. XELJANZ had been approved and is approved, and you see in the United States. But basically, it had very low adoption. We're seeing now in the community that 70% of the prescriptions are coming from physicians that have never written a JAK before. So it shows you that the clinical profile of Rinvoq in terms of its speed and the depth of the response is being viewed very, very well. So not only is that encouraging for Rinvoq. You see, as I mentioned, we're going to have the approval for Crohn's for Rinvoq in later lines next year as well.

因此，我們已經看到快速採用。正如我所提到的，在美國的 Rinvoq 將是基於標籤的二線 plus，我們看到非常非常快的採用。我會給你一些顏色。 XELJANZ 已經被批准和被批准，你在美國看到。但基本上，它的採用率很低。我們現在在社區中看到 70% 的處方來自以前從未寫過 JAK 的醫生。因此，它向您展示了 Rinvoq 在其速度和響應深度方面的臨床概況正在被非常、非常好地看待。因此，這不僅對 Rinvoq 是鼓舞人心的。你看，正如我所提到的，我們也將在明年的晚些時候獲得克羅恩對 Rinvoq 的批准。

Skyrizi continues to surprise us to the upside, as you've heard from the call today. This is viewed increasingly as the preferred frontline drug coming straight out of the gate for Crohn's in the U.S. And the qualitative data that we're starting to see, and we are seeing some quantitative data that looks very strong, too, is that this is -- as a -- already as a best-in-class product for Crohn's, which is a very, very substantial market.

正如您從今天的電話中聽到的那樣，Skyrizi 繼續給我們帶來驚喜。這被越來越多地視為美國克羅恩病的首選一線藥物。我們開始看到的定性數據，我們看到一些看起來也非常強大的定量數據，是- 作為 - 已經成為 Crohn's 的一流產品，這是一個非常非常龐大的市場。

So we are very encouraged. We continue to say that the IBD is probably underappreciated, and we'll continue to give updates as these launches progress.

所以我們很受鼓舞。我們繼續說 IBD 可能被低估了，隨著這些發布的進展，我們將繼續提供更新。

So Gary, this is Rob. I'll take your question on OpEx. If you look at the benefit we're seeing, about half of it is actually coming from the stronger U.S. dollar, so it's more of an FX impact. The other half is spend productivity. We always look for opportunities to drive more productivity in our spend. It's not so much about scaling back in parts of the business, we always look for ways to spend better, buy better. And ultimately, that helps us. In many cases also, over the long term, redeploy that investment to drive growth.

加里，這是羅伯。我會回答你關於 OpEx 的問題。如果你看看我們看到的好處，其中大約一半實際上來自美元走強，所以它更多的是對外彙的影響。另一半是支出生產力。我們一直在尋找機會來提高我們的支出效率。與其說是縮減部分業務，我們總是在尋找更好的消費方式，更好的購買方式。最終，這對我們有幫助。在許多情況下，從長遠來看，重新部署投資以推動增長。

If you think about '23, I've said -- given that 46% to 47% operating margin directional input. I've also said we're not going to cut back investment. We'll obviously be prudent given that you will see a decline in gross margins next year, but we're not going to be cutting back investment because we expect to return to growth quickly. So you'll see us not necessarily cut back, but certainly put more behind this business to drive that long-term growth that we expect to be industry-leading over the long term.

如果你想想 23 年，我說過 - 考慮到 46% 到 47% 的營業利潤率方向性輸入。我也說過我們不會削減投資。鑑於明年毛利率會下降，我們顯然會謹慎行事，但我們不會削減投資，因為我們預計會迅速恢復增長。因此，您會看到我們不一定會削減開支，但肯定會為這項業務投入更多資金，以推動我們預計長期處於行業領先地位的長期增長。

Thanks, Gary.

謝謝，加里。

Our next question comes from Colin Bristow from UBS.

我們的下一個問題來自瑞銀的 Colin Bristow。

So first on CF, you recently posted an updated clinical trials for your new C2 corrector-based regimen. I just wondered if you could walk us through what gives you confidence that this has a higher probability of success versus your last deterioration?

因此，首先在 CF 上，您最近發布了針對您的新 C2 校正方案的更新臨床試驗。我只是想知道你是否能告訴我們是什麼讓你相信這比你上次的惡化更有可能成功？

And then second one for Rick, I just wanted to touch base on your succession plan. It's been an increasingly sort of important or a frequent topic with investors. You've been the architect of AbbVie's success since inception. And so just wanted to confirm specifically how long you expect to stay in the seat? And then how should we think about the time lines around the process of identifying your successor?

然後是 Rick 的第二個，我只是想談談你的繼任計劃。對於投資者來說，這已成為越來越重要或經常出現的話題。自 AbbVie 成立以來，您就是成功的建築師。所以只是想具體確認您希望在座位上停留多長時間？然後我們應該如何考慮確定繼任者的時間線？

This is Tom, I'll answer the CF question. Again, this is very challenging to actually make that abnormal CF protein get to the membrane and act as a chloride channel, and it takes 3 different drugs to make it effectively to get it to the cell membrane and open up in the right way. And so we all felt that we had [intakes], we call them Corrector 1, Corrector 2 and Potentiators, these 3 different compounds. We always see good results with double our C1 corrector. We think it's best-in-class. Our potentiator is very good. What we had difficulty is to get a good C2 corrector, and what I presented earlier this year was that it wasn't good enough.

我是湯姆，我會回答 CF 問題。再次，讓異常的 CF 蛋白真正進入細胞膜並充當氯離子通道是非常具有挑戰性的，並且需要 3 種不同的藥物才能使其有效地到達細胞膜並以正確的方式打開。所以我們都覺得我們有[攝入量]，我們稱它們為 Corrector 1、Corrector 2 和 Potentiators，這 3 種不同的化合物。我們總是看到使用雙倍 C1 校正器的良好結果。我們認為它是一流的。我們的增效劑非常好。我們遇到的困難是獲得一個好的 C2 校正器，而我今年早些時候提出的是它還不夠好。

But what we've done since then, we will continue to look at better ones and we came out with a differentiated product, [576], which is structurally different. And the data supports higher safety margin, higher exposures, good PK. Hopefully, a single pill. And then we'd be able to get to this -- to be able to have this triplet which is really important to be competitive.

但是從那以後我們所做的，我們將繼續尋找更好的產品，我們推出了一個差異化的產品，[576]，它在結構上是不同的。並且數據支持更高的安全邊際、更高的曝光度、良好的PK。希望是一粒藥。然後我們就能夠做到這一點——能夠擁有這個對競爭力非常重要的三胞胎。

So again, our doublet, the data we had was very strong. But we need that third piece, and that third piece seems to be coming along really well. That's what you really saw on the west side at ct.gov is we're moving to evaluate this triple combo with our new C2 corrector.

再說一次，我們的雙峰，我們擁有的數據非常強大。但是我們需要第三部分，而第三部分似乎進展順利。這就是您在 ct.gov 西側真正看到的情況，我們正在使用我們的新 C2 校正器來評估這個三重組合。

And this is Rick on the succession question. I'd say that we obviously have a very experienced Board, and we've had an active approach on succession going back to about 2016, 2017. And that process has proceeded extremely well in developing internal candidates to ultimately assume the role when I do retire.

這是關於繼任問題的里克。我想說的是，我們顯然有一個非常有經驗的董事會，我們在繼任方面採取了積極的做法，可以追溯到 2016 年和 2017 年左右。這個過程在培養內部候選人方面進展得非常好，最終在我擔任該職位時進行退休。

I can tell you that there are no plans at all for me to retire in 2023. The most important thing to me and to the Board is to make sure that the business is performing exactly as we expect going forward, and we're not going to make any transition until we've gone through the biosimilar event, and we're confident in the performance of the overall business. That would be the appropriate time once we're confident to make a transition at that point.

我可以告訴你，我根本沒有計劃在 2023 年退休。對我和董事會來說，最重要的是確保業務的表現完全符合我們的預期，而且我們不會去在我們完成生物類似藥事件之前進行任何過渡，並且我們對整體業務的表現充滿信心。一旦我們有信心在那個時候進行過渡，那將是合適的時間。

We've also had discussions with the Board of what that transition would look like. And assuming it's an internal candidate, the transition will essentially work where we will name a new CEO. And at that point, I will assume him the role of Executive Chair for a period of time thereafter.

我們還與董事會討論了這種過渡會是什麼樣子。假設它是內部候選人，那麼過渡基本上將在我們任命新 CEO 的地方進行。屆時，我將在此後的一段時間內擔任他的執行主席一職。

So I think we have a well-thought-out succession approach. I feel very comfortable with the approach, I feel comfortable with the work we're doing to develop the internal candidates. And I think the transition when it occurs, I think, will go smoothly and be successful. So hopefully, that answers your question.

所以我認為我們有一個深思熟慮的繼任方法。我對這種方法感到非常滿意，我對我們為培養內部候選人所做的工作感到滿意。我認為，一旦發生過渡，我認為會順利進行並取得成功。所以希望這能回答你的問題。

Thanks, Colin.

謝謝，科林。

Our next question comes from Chris Shibutani from Goldman Sachs.

我們的下一個問題來自高盛的 Chris Shibutani。

Chris, are you there? We can't hear you.

克里斯，你在嗎？我們聽不見你的聲音。

Yes. Apologies. Two questions, if I may. On Rinvoq, you had previously commented that you were seeing some use in the first-line setting. Can you update us at all with any color there?

是的。道歉。兩個問題，如果可以的話。在 Rinvoq 上，您之前曾評論說您在一線設置中看到了一些用途。你能用那裡的任何顏色更新我們嗎？

Secondly, for Skyrizi, obviously, a very attractive market and an opportunity in Crohn's disease. Can you show us how you're thinking about the potential impact given the LOE in 2023 of a major branded players, STELARA?

其次，對於 Skyrizi 來說，顯然是一個非常有吸引力的市場，也是克羅恩病的機會。鑑於主要品牌玩家 STELARA 在 2023 年的 LOE，您能否向我們展示您如何看待潛在影響？

Chris, it's Jeff. Just to clarify in terms of your Rinvoq question, was there a specific question related to a certain indication on the front line? Or I'm not sure I fully appreciate that one.

克里斯，我是傑夫。只是為了澄清您的 Rinvoq 問題，是否有與前線的某個指示相關的具體問題？或者我不確定我是否完全欣賞那個。

Yes, no. In AD.

是的，沒有。在廣告中。

In AD, okay, right. So yes, we do see frontline use across the globe and even in the U.S. And what we're seeing is now, as I mentioned in my remarks, we're seeing in-line in-play share, which is in the high mid-teens right now in the U.S., and it's higher in the international markets. So there seems to be, as we look to the research and we look to our market -- end market performance, there's really 2 segments of dermatologists. There's very cautious dermatologists that are slow to adopt JAKs, and typically, they'll start in the later line, a second line plus.

在 AD 中，好吧，對。所以，是的，我們確實看到了全球甚至美國的一線使用。正如我在講話中提到的，我們現在看到的是，我們看到的是在線遊戲中的份額，它處於中高端- 現在美國的青少年，在國際市場上更高。因此，當我們著眼於研究和我們的市場——終端市場表現時，似乎確實有 2 個皮膚科醫生細分市場。非常謹慎的皮膚科醫生採用 JAK 的速度很慢，通常他們會從後一行開始，即第二行加。

There is an emerging cohort of a significant group of dermatologists as well that basically are looking at the underlying high efficacy parameters, so basically like the EASI 90 skin clearance and almost no discernible itch for the product. They typically are starting to use more and more in the front line. So the overall balance is leaning towards the second line, but we do see increasing frontline utilization based on the profile of the drug in atopic dermatitis.

還有一批重要的皮膚科醫生，他們基本上都在研究潛在的高效參數，所以基本上就像 EASI 90 皮膚清除率和產品幾乎沒有明顯的瘙癢。他們通常開始在前線使用越來越多的人。因此，總體平衡傾向於第二線，但我們確實看到基於藥物在特應性皮炎中的概況增加的一線利用率。

In terms of the Skyrizi for Crohn's, we think we're very, very well positioned for a couple of reasons. One is the overall profile of the medicine is really exceptional, as I've highlighted, and we're going to see very, very rapid adoption both in the U.S. and the external market. In addition, we have anticipated the STELARA LOE. We see that we have an ongoing head-to-head trial versus STELARA to make sure that we can continue to differentiate with direct data that will come over the next year or so, so we're anticipating that. And we think we're going to have a good setup to maintain the early momentum that we're seeing with Skyrizi.

就 Crohn's 的 Skyrizi 而言，我們認為我們處於非常非常有利的位置，原因有兩個。一是藥物的整體概況非常出色，正如我已經強調的那樣，我們將在美國和外部市場看到非常非常迅速的採用。此外，我們已經預料到了 STELARA LOE。我們看到我們正在進行與 STELARA 的正面對比試驗，以確保我們可以繼續通過將在明年左右出現的直接數據進行區分，因此我們對此有所期待。我們認為我們將有一個良好的設置來保持我們在 Skyrizi 看到的早期勢頭。

Thanks, Chris.

謝謝，克里斯。

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

我們的下一個問題來自美國銀行的 Geoff Meacham。

I just have one quick one. Rick, lots of questions on Humira for next year, but I wanted to ask at a high level on the environment beyond that. I know there are formal treatment guidelines in I&I, but what's the risk that payers mandate cycling through one or more biosimilars? And what's the risk -- the pricing environment doesn't really recover in '24 and beyond? Just obviously thinking about the Skyrizi and Rinvoq franchises over the long term?

我只有一個快速的。瑞克，明年有很多關於修美樂的問題，但我想就除此之外的環境提出更高層次的問題。我知道 I&I 中有正式的治療指南，但是付款人要求循環使用一種或多種生物仿製藥的風險是什麼？風險是什麼——定價環境在 24 年及以後並沒有真正恢復？只是從長遠來看顯然是在考慮 Skyrizi 和 Rinvoq 的特許經營權？

So I'm actually going to have Jeff walk you through that. He's probably the closest to that environment.

所以我實際上會讓 Jeff 引導你完成。他可能是最接近那個環境的人了。

Yes, so thank you for the question. I mean, one of the things that we see certainly in the near term is that the formularies in I&I are actually expanding. So many years ago, you might have 6 or 7 preferred agents. The payers are now requesting sometimes up to 11 or 12 preferred agents, so you're seeing an expansive nature in the short term. Now as you go forward, maybe middle of the decade or later where you have more and more biosimilars, could the U.S. environment move towards sort of a step through? I mean, it's possible. But we have, again, as I mentioned in my last statement, we have anticipated that with the right types of data, the trials. We have 5 head-to-head studies in Skyrizi in psoriasis, we have more coming in Crohn's. And so we think that basically, we have a data-driven approach that's going to continue to allow us to significantly differentiate our products.

是的，所以謝謝你的問題。我的意思是，我們在短期內肯定會看到的一件事是 I&I 中的處方集實際上正在擴大。這麼多年前，您可能有 6 或 7 個首選代理。付款人現在有時會要求最多 11 或 12 個首選代理，因此您會在短期內看到擴展性。現在，隨著您繼續前進，可能在十年中或更晚，您擁有越來越多的生物仿製藥，美國環境能否邁出一步？我的意思是，這是可能的。但是，正如我在上一次聲明中提到的那樣，我們再次預測到有了正確類型的數據，試驗。我們在 Skyrizi 進行了 5 項針對銀屑病的面對面研究，我們在克羅恩病中進行了更多研究。所以我們認為，基本上，我們有一種數據驅動的方法，它將繼續使我們能夠顯著區分我們的產品。

The other dynamic that we watch very carefully, and we talked about this during the Immunology Investor Day, is the lines of therapy as there's more and more high efficacy products that get introduced, continue to expand. So in the middle of the decade or longer, the second plus and the third line market are going to be very, very significant at that point.

我們非常仔細觀察的另一個動態，我們在免疫學投資者日期間談到了這一點，是治療線，因為有越來越多的高效產品被引入，繼續擴大。因此，在十年中期或更長時間，二線和三線市場將非常非常重要。

So when we put all of that into the calculus we feel, again, we have a pretty set up for the middle of the decade and longer.

因此，當我們將所有這些都放入微積分中時，我們再次感覺到，我們已經為這十年的中期或更長時間做好了準備。

And this is Rick. I agree with everything Jeff said. The one thing I would add that as you think about even under a scenario where if we did get to some kind of a step at it, you have to go back and remember that most of these mechanisms, most patients fail, and they fail at a relatively high level and over a relatively short period of time. So even if you had to rotate through you're going to get to second line relatively quickly, and recycling somebody back through another TNF typically doesn't work very well for those patients.

這是瑞克。我同意傑夫所說的一切。我要補充的一件事是，即使在這樣一種情況下，即使我們確實取得了某種進展，您也必須回過頭來記住這些機制中的大多數，大多數患者都失敗了，而且他們失敗了相對較高的水平和相對較短的時間。因此，即使您必須輪換，您也將相對較快地進入二線，並且通過另一種 TNF 回收某人通常對這些患者效果不佳。

And I'd say the demand now with the kind of agents that we have in the market now and the level of remission that they can create, the demand among physicians is much higher to get patients into remission as rapidly as they possibly can. And so I think all those dynamics tell us that this model should continue to work over the long haul.

我想說的是，我們現在市場上的那種藥物的需求以及它們可以創造的緩解水平，醫生之間的需求要高得多，以使患者盡快得到緩解。因此，我認為所有這些動態都告訴我們，這種模式應該會繼續長期有效。

Thanks, Jeff. I believe we have taken all the questions in the queue, so 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，傑夫。我相信我們已經回答了隊列中的所有問題，今天的電話會議到此結束。如果您想收聽電話重播，請訪問我們的網站investors.abbvie.com。再次感謝您加入我們。

Thank you. This does conclude today's conference. You may disconnect at this time.

謝謝你。今天的會議到此結束。此時您可以斷開連接。