葛蘭素史克 (GSK) 2022 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the analyst call of GSK Fourth Quarter 2020 Results.

女士們先生們，下午好，歡迎來到 GSK 2020 年第四季度業績的分析師電話會議。

I will now hand you over to Nick Stone, Head of Global Investor Relations, who will introduce today's session.

現在我將把你們交給全球投資者關係主管 Nick Stone，他將介紹今天的會議。

Thank you, operator. Hello, everyone. Welcome to our full year and Q4 2022 conference call and webcast for investors and analysts. The presentation was sent to our distribution list by e-mail earlier today, and you can also find details under gsk.com.

謝謝你，運營商。大家好。歡迎來到我們面向投資者和分析師的全年和 2022 年第四季度電話會議和網絡直播。該演示文稿已於今天早些時候通過電子郵件發送到我們的通訊組列表，您還可以在 gsk.com 下找到詳細信息。

Please turn to Slide 2. This is the usual safe harbor statement. We will comment on our performance using constant exchange rates, or CER, unless stated otherwise. As a reminder, the Consumer Healthcare business was demerged on 18th of July 2022 to form Haleon. But today, we're presenting continuing operations for GSK.

請轉到幻燈片 2。這是通常的安全港聲明。除非另有說明，否則我們將使用固定匯率或 CER 對我們的表現進行評論。提醒一下，消費者保健業務於 2022 年 7 月 18 日分拆成立了 Haleon。但今天，我們將展示 GSK 的持續運營。

Please turn to Slide 3. Today's management presentation will last approximately 30 minutes with the remaining 30 minutes for your questions, and this is to ensure that we get you to your next call, given it's such a busy day for those on the street.

請轉到幻燈片 3。今天的管理演示將持續大約 30 分鐘，剩下的 30 分鐘用於您的問題，這是為了確保我們能接聽您的下一個電話，因為今天對街上的人來說是如此忙碌。

(Operator Instructions) Our speakers are Emma Walmsley, Tony Wood, Luke Miels, Deborah Waterhouse, and Iain MacKay with David Redfern joining the rest of the team for Q&A.

（操作員說明）我們的發言人是 Emma Walmsley、Tony Wood、Luke Miels、Deborah Waterhouse 和 Iain MacKay，David Redfern 與其他團隊成員一起進行問答。

Please turn to Slide 4, and I'll now hand the call over to Emma.

請轉到幻燈片 4，我現在將電話轉給 Emma。

Thanks, Nick, and welcome to everyone. Please turn to the next slide. 2022 was a landmark year for GSK. We successfully delivered the most significant corporate change in 20 years and began a new chapter of competitive and profitable growth. GSK is a most global biopharma company with the ambition and purpose to unite science, technology and talent to get ahead of disease together. We are a world leader in the prevention and treatment of infectious diseases with an industry-leading vaccines franchise that continues to strengthen and expertise in HIV that is pioneering in innovation, and we have an exciting emerging pipeline based on the science of the immune system.

謝謝，尼克，歡迎大家。請翻到下一張幻燈片。 2022 年對葛蘭素史克來說是具有里程碑意義的一年。我們成功地實現了 20 年來最重大的企業變革，開啟了競爭和盈利增長的新篇章。 GSK 是一家最俱全球性的生物製藥公司，其雄心和宗旨是聯合科學、技術和人才，共同戰勝疾病。我們在預防和治療傳染病方面處於世界領先地位，擁有行業領先的疫苗特許經營權，該特許經營權不斷加強，並在 HIV 領域擁有專業知識，是創新的先驅，我們擁有令人興奮的基於免疫系統科學的新興管道。

Through ongoing focus on R&D productivity and operating performance, we're unlocking the potential of this company. We are realizing our bold ambitions reflected in our commitment to attractive growth and a significant step change in delivery. And through the demerger of Haleon, our world leading consumer healthcare business in its own right, we've strengthened our balance sheet, creating additional flexibility to invest in continuing growth and innovation.

通過持續關注研發生產力和運營績效，我們正在釋放這家公司的潛力。我們正在實現我們的雄心壯志，這反映在我們對有吸引力的增長和交付方式發生重大變化的承諾中。通過分拆我們世界領先的消費者保健業務 Haleon，我們加強了資產負債表，為投資持續增長和創新創造了更大的靈活性。

Turning to Slide 6. I'm delighted with today's results, which demonstrate that our strategy is driving the step change in financial performance we committed to with continued strong momentum as we enter 2023. In 2022, we delivered double-digit sales growth of 13%, 10% if you exclude COVID solutions, including the more than GBP 2 billion sales of Xevudy; adjusted operating profit growth of 14%, 17% excluding COVID solutions; adjusted EPS growth of 15% and strong free cash flow of GBP 3.3 billion, further strengthening our financial flexibility.

轉到幻燈片 6。我對今天的結果感到滿意，這表明我們的戰略正在推動我們承諾的財務業績的階躍變化，並在我們進入 2023 年時繼續保持強勁勢頭。到 2022 年，我們實現了兩位數的銷售額增長 13 %，如果排除 COVID 解決方案，則為 10%，包括 Xevudy 超過 20 億英鎊的銷售額；調整後的營業利潤增長 14%，不包括 COVID 解決方案為 17%；調整後的每股收益增長 15% 和 33 億英鎊的強勁自由現金流，進一步增強了我們的財務靈活性。

This outstanding performance was driven by strong sales growth across both Specialty Medicines and Vaccines, alongside continued pipeline progress and underpins our guidance today. In 2023, excluding COVID solutions, we expect sales to increase between 6% and 8%, adjusted operating profit to increase between 10% and 12% and adjusted EPS growth between 12% and 15%.

這一出色的業績是由專業藥物和疫苗的強勁銷售增長以及持續的管道進展推動的，並鞏固了我們今天的指導。到 2023 年，不包括 COVID 解決方案，我們預計銷售額將增長 6% 至 8%，調整後的營業利潤將增長 10% 至 12%，調整後的每股收益增長將在 12% 至 15% 之間。

Please turn to Slide 7. The strong delivery in 2022 and commitment to do so again this year supports our increased confidence in all dimensions of these 26 outlooks and demonstrate the continuing successful momentum in our transformation of GSK. Our portfolio mix has meaningfully shifted to Vaccines and Specialty Medicines, now approaching 2/3 of our sales in 2022 compared to 46% in 2017. This evolving portfolio shape and our prioritized investments in innovation and product launches with good cost discipline are reflected in our continuing margin expansion.

請轉到幻燈片 7。2022 年的強勁交付和今年再次這樣做的承諾支持了我們對這 26 項展望的所有方面的信心增強，並證明了我們在 GSK 轉型中持續的成功勢頭。我們的產品組合已有意義地轉向疫苗和特殊藥物，目前占我們銷售額的 2/3，而 2017 年為 46%。這種不斷變化的產品組合形態以及我們在創新和產品發布方面的優先投資以及良好的成本紀律反映在我們的利潤率持續擴張。

Please turn to Slide 8. Before handing over to Tony for more detail, I'd like to share a couple of headlines on our progress in reshaping and advancing our pipeline, our #1 priority. We've built a pipeline of 69 vaccines and medicines, many with the potential to be first or best-in-class. We've also had over 20 new approvals in the last 5 years, now representing nearly 1/3 of our 2022 sales, excluding COVID Solutions, and we anticipate more regulatory decisions this year.

請轉到幻燈片 8。在交給托尼了解更多細節之前，我想分享幾個關於我們在重塑和推進管道方面取得進展的頭條新聞，這是我們的第一要務。我們已經建立了 69 種疫苗和藥物的產品線，其中許多有可能成為一流或一流的。在過去 5 年中，我們還獲得了 20 多項新批准，現在占我們 2022 年銷售額的近 1/3，不包括 COVID 解決方案，我們預計今年會有更多監管決定。

Our 2022 achievements include the launch of Apretude, first and only long act injectable for HIV prevention, alongside Cabenuva, the first and only complete long-acting HIV treatment regimen. We intend to continue to lead in changing the landscape for people living with HIV around the world over the coming years. In Vaccines, the key highlight was our exceptional RSV older adult data that led to a prompt regulatory submission and priority review acceptance by the U.S. FDA. Our vaccine candidate has a potential best-in-class profile and represents a significant commercial opportunity with multibillion Shingrix life potential.

我們 2022 年的成就包括推出 Apretude，這是第一個也是唯一一個用於預防 HIV 的長效注射劑，以及第一個也是唯一一個完整的長效 HIV 治療方案 Cabenuva。我們打算在未來幾年繼續引領改變世界各地艾滋病病毒感染者的面貌。在疫苗方面，關鍵亮點是我們出色的 RSV 老年人數據，這導緻美國 FDA 迅速提交監管文件並接受優先審查。我們的候選疫苗具有潛在的同類最佳特性，代表著具有數十億 Shingrix 生命潛力的重要商業機會。

We also made some important advances in the clinical development of 2 late-stage assets, gepotidacin and new novel antibiotic for uncomplicated UTIs and bepirovirsen, which has the potential to provide a first-in-class functional cure for chronic Hep B. Strategic business development also played an important role in reshaping our pipeline, the acquisitions of Sierra Oncology and Affinivax complement our portfolio, and in the case of Affinivax, give us access to not only a Phase II next-gen 24 million new COVID vaccine, but also the Novamax platform technology to target complex pathogens that have multiple serotypes.

我們還在 2 個後期資產的臨床開發方面取得了一些重要進展，gepotidacin 和用於簡單 UTI 的新型抗生素和 bepirovirsen，有可能為慢性乙肝提供一流的功能性治療。戰略業務發展在重塑我們的管道方面也發揮了重要作用，對 Sierra Oncology 和 Affinivax 的收購補充了我們的產品組合，就 Affinivax 而言，使我們不僅可以獲得第二階段的下一代 2400 萬新 COVID 疫苗，還可以獲得 Novamax針對具有多种血清型的複雜病原體的平台技術。

We have a world-leading profile in infectious diseases and an exciting portfolio and pipeline based on the science of the immune system that we're confident will sustain growth through this decade and beyond.

我們在傳染病領域擁有世界領先的地位，以及基於免疫系統科學的令人興奮的產品組合和管道，我們有信心在這十年及以後保持增長。

I'll now hand it over to Tony for more details.

我現在將其交給 Tony 以了解更多詳細信息。

Thank you, Emma. Next slide, please. Today, I will talk about recent R&D developments and preview important events that will shape our pipeline. In 2022, nearly 1/3 of our sales came from assets launched in the prior 5 years, and we are confident that our early-stage pipeline is well positioned. In terms of continued strong commercial execution to deliver our 2031 ambitions.

謝謝你，艾瑪。請換下一張幻燈片。今天，我將討論最近的研發進展，並預覽將影響我們管道的重要事件。到 2022 年，我們近 1/3 的銷售額來自前 5 年推出的資產，我們相信我們的早期產品線定位良好。在持續強勁的商業執行方面，以實現我們 2031 年的雄心壯志。

This slide illustrates our focus in 4 key therapeutic areas, shaped by our world-leading capabilities in infectious diseases, our understanding of the science of the immune system and human genetics. In 2022, we progressed 60 novel candidates into the clinic, added 9 to Phase II and started 5 Phase III programs, which reflected our core therapeutic focus, including the initiation of Phase III life cycle innovation trials for depemokimab in eosinophilic disease and cobolimab for the treatment of non-small cell lung cancer. So today, our pipeline comprises 22 vaccines and 47 medicines, many of which are potential first or best in class. These novel programs will form the basis for our next wave of pipeline innovation and growth.

這張幻燈片說明了我們在 4 個關鍵治療領域的重點，這些領域由我們在傳染病領域的世界領先能力、我們對免疫系統科學和人類遺傳學的理解所塑造。 2022 年，我們有 60 名新候選藥物進入臨床，9 名進入 II 期，並啟動 5 個 III 期項目，這反映了我們的核心治療重點，包括啟動了用於嗜酸性粒細胞疾病的 depemokimab 和用於非小細胞肺癌的治療。所以今天，我們的管道包括 22 種疫苗和 47 種藥物，其中許多可能是一流的或一流的。這些新穎的項目將構成我們下一波管道創新和增長的基礎。

I'm pleased with our continued progress and the next slide shows some highlights from last year. In 2022, our highest profile result was the publication of the Phase III data for our RSV older adult vaccine candidate. This demonstrated 94% protection against severe disease with consistent and sustained high efficacy against both RSV A and E strains in people in their 70s and in those with comorbidities. Our global regulatory submissions include data showing that the vaccine can be safely co-administered with a flu vaccine without diminishing the effect either. Following regulatory submission, we received a priority review from the U.S. FDA, and we anticipate a regulatory decision in early May.

我對我們的持續進步感到滿意，下一張幻燈片展示了去年的一些亮點。 2022 年，我們最引人注目的結果是發布了我們的 RSV 老年成人候選疫苗的 III 期數據。這表明 70 多歲的人和患有合併症的人對嚴重疾病的保護率達到 94%，並且對 RSV A 和 E 毒株具有一致和持續的高效能。我們提交的全球監管意見書包括的數據表明，該疫苗可以安全地與流感疫苗共同接種，而不會降低效果。在提交監管申請後，我們收到了美國 FDA 的優先審查，我們預計將在 5 月初做出監管決定。

Our ongoing Phase III trial continues to collect data and will determine if protection extends beyond one season. We anticipate generating second season data in time for the June ACIP meeting. Additionally, we're also recruiting a Phase III trial examining effectiveness in protecting adults aged 50 and above who are at higher risk of developing severe disease.

我們正在進行的 III 期試驗將繼續收集數據，並將確定保護是否超過一個賽季。我們預計會及時為 6 月的 ACIP 會議生成第二季數據。此外，我們還在招募一項 III 期試驗，以檢驗在保護 50 歲及以上患重病風險較高的成年人方面的有效性。

It's important that I mention the ongoing development of Shingrix. We presented data last year showing that Shingrix provides overall efficacy of greater than 80% over a follow-up period of 6 to 10 years after the initial vaccination. These 10-year data were generated as part of our ongoing life cycle innovation, and we regularly review Shingrix's duration of protection and the potential need for a booster. These data will inform the next steps in clinical development, and I'll keep you updated with progress.

重要的是我要提到 Shingrix 的持續發展。我們去年提交的數據顯示，在初次接種疫苗後 6 至 10 年的隨訪期內，Shingrix 的總體療效超過 80%。這些 10 年的數據是我們正在進行的生命週期創新的一部分，我們會定期審查 Shingrix 的保護持續時間和對助推器的潛在需求。這些數據將為臨床開發的後續步驟提供信息，我會及時向您通報最新進展。

In HIV, we are committed to improving the existing treatment options for people living with HIV. We have an exciting pipeline including options for self-administration and ultra long-acting medicines. We're also investigating new approaches to HIV treatment. Last year, we presented proof-of-concept data from the Phase II banner trial for N6LS, our broadly neutralizing antibody. This is one of several exciting opportunities within our HIV portfolio, and we remain on track to move this into Phase III development in 2024.

在艾滋病毒方面，我們致力於改善艾滋病毒感染者現有的治療方案。我們有一個令人興奮的管道，包括自我管理和超長效藥物的選擇。我們還在研究治療 HIV 的新方法。去年，我們展示了我們的廣泛中和抗體 N6LS II 期橫幅試驗的概念驗證數據。這是我們 HIV 產品組合中幾個令人興奮的機會之一，我們仍有望在 2024 年將其推進 III 期開發。

Oncology is an emerging therapeutic area. We reported positive high-level results for Jemperli Phase III RUBY trial, which met its primary endpoint, the first trial to show a PFS benefit for an I-O agent in the treatment of women with primary advanced or recurrent endometrial cancer. These data may support the use of Jemperli in the first-line setting. We also decided to progress all arms of the COSTAR lung trial into Phase III. This compares cobolimab and dostarlimab combinations in treating patients with advanced non-small cell lung cancer, a large patient population with significant unmet medical need, and we expect to see data from this trial in 2024.

腫瘤學是一個新興的治療領域。我們報告了 Jemperli III 期 RUBY 試驗的高水平陽性結果，該試驗達到了其主要終點，這是第一個顯示 I-O 藥物治療原發性晚期或複發性子宮內膜癌女性 PFS 獲益的試驗。這些數據可能支持在一線設置中使用 Jemperli。我們還決定將 COSTAR 肺部試驗的所有組推進到 III 期。這比較了 cobolimab 和 dostarlimab 組合治療晚期非小細胞肺癌患者的情況，這些患者群體很大，醫療需求未得到滿足，我們預計 2024 年會看到該試驗的數據。

In 2022, we progressed several Phase I programs and reported positive proof-of-concept data. Revax last year, includes data from our randomized Phase Ib trial of CCL17 in osteoarthritis, demonstrating evidence of efficacy at the end of the 8-week dosing period. We plan to progress development and we'll share more later this year. Our partner, CureVac also announced interim Phase I data for flu and COVID mRNA vaccines.

2022 年，我們推進了幾個第一階段項目，並報告了積極的概念驗證數據。去年的 Revax 包括來自我們的 CCL17 骨關節炎隨機 Ib 期試驗的數據，證明了在 8 週給藥期結束時的療效證據。我們計劃推進開發，我們將在今年晚些時候分享更多。我們的合作夥伴 CureVac 還公佈了流感和 COVID mRNA 疫苗的中期 I 期數據。

These preliminary data provide promising evidence of activity, which included a monovalent flu vaccine that successfully boosted antibody titers against a matching flu strain even at the lowest dose. Based on these promising data, we believe there is a significant opportunity to accelerate the development based on this technology. We're excited about the potential of doublet vaccines, and we're pleased with the progress we're making on both the COVID and influenza projects.

這些初步數據提供了有希望的活動證據，其中包括一種單價流感疫苗，即使在最低劑量下也能成功提高針對匹配流感病毒株的抗體滴度。基於這些有前途的數據，我們相信有一個重要的機會來加速基於這項技術的發展。我們對雙重疫苗的潛力感到興奮，我們對我們在 COVID 和流感項目上取得的進展感到高興。

As Emma mentioned, we also completed several business development deals in 2022, enhancing our portfolio and platform technology. These deals supplement our late-stage pipeline to support further growth and deliver our R&D strategy. BD and capital allocation will be a strong focus in 2023 and beyond. We also announced a collaboration with Wave Life Sciences to enhance our discovery and development capabilities using novel oligonucleotides.

正如 Emma 提到的，我們還在 2022 年完成了幾項業務發展交易，增強了我們的產品組合和平台技術。這些交易補充了我們的後期管道，以支持進一步增長並實現我們的研發戰略。 BD 和資本配置將成為 2023 年及以後的重點。我們還宣布與 Wave Life Sciences 合作，以使用新型寡核苷酸增強我們的發現和開發能力。

Now I'd like to provide a brief details on the progress of our most advanced oligonucleotide, bepirovirsen. Next slide, please. I'm particularly excited to disclose that the first patient has been recruited into the B-WELL Phase III program for bepirovirsen in the treatment of hepatitis B patients with low baseline surface antigen. Remember that in our Phase II trial B-CLEAR, we observed that an unprecedented number of patients treated with low baseline surface antigen experienced sustained Hep B surface antigen and DNA loss at the end of the 48-week study period.

下面我簡單介紹一下我們最先進的寡核苷酸貝匹羅韋森的進展情況。請換下一張幻燈片。我特別興奮地宣布，第一位患者已被招募到 B-WELL III 期項目中，使用貝匹羅韋森治療低基線表面抗原的乙型肝炎患者。請記住，在我們的 II 期試驗 B-CLEAR 中，我們觀察到在 48 週研究期結束時，接受低基線表面抗原治療的患者數量空前地經歷了持續的乙肝表面抗原和 DNA 丟失。

Hepatitis B infection is a significant unmet medical need with over 300 million people having this chronic disease and around 900,000 who die from liver disease-related consequences. The current standard of care achieves functional cure in fewer than 5% of patients, and managing the disease places a significant burden on global health care systems.

乙型肝炎感染是一項未得到滿足的重大醫療需求，超過 3 億人患有這種慢性疾病，約 90 萬人死於與肝病相關的後果。目前的護理標准在不到 5% 的患者中實現了功能性治愈，並且管理這種疾病給全球醫療保健系統帶來了沉重的負擔。

Our aim is for bepirovirsen to become a backbone of future therapy. Around Moderna, I also look forward to sharing data from B-TOGETHER. A Phase II trial that administers bepirovirsen followed by interferon therapy with the goal of improving functional cure rates still further.

我們的目標是讓貝匹羅韋森成為未來治療的支柱。圍繞Moderna，我也很期待分享B-TOGETHER的數據。一項 II 期試驗，先給予貝匹羅韋森，然後進行干擾素治療，目的是進一步提高功能性治愈率。

Next slide, please. In November, we reported that 2 Phase III gepotidacin trials for the treatment of uncomplicated urinary tract infections were stopped early for efficacy after a successful interim analysis. Data collection and analysis are ongoing, and we anticipate making a regulatory submission later this year. The world needs new classes of antibiotics, treatment failure increasing community resistance rates and increasing safety warnings for existing medicines, including fluroquinolones are reducing the available oral options for uncomplicated UTIs. If approved, gepotidacin would become the first new oral antibiotic for the treatment of uncomplicated UTI for over 20 years. Unmet medical need is significant with around 15 million episodes of uncomplicated infection in the U.S. alone, a 1/4 of which occur or have some level of resistance. Gepotidacin would be positioned as an oral option for patients at risk of treatment failure.

請換下一張幻燈片。 11 月，我們報告了 2 項用於治療無並發症尿路感染的 III 期吉泊達星試驗在中期分析成功後因療效而提前停止。數據收集和分析正在進行中，我們預計將在今年晚些時候提交監管文件。世界需要新型抗生素，治療失敗增加了社區耐藥率，增加了對現有藥物（包括氟喹諾酮類藥物）的安全警告正在減少無並發症 UTI 的可用口服選擇。如果獲得批准，gepotidacin 將成為 20 多年來第一個用於治療無並發症 UTI 的新型口服抗生素。未滿足的醫療需求很大，僅在美國就有大約 1500 萬例無並發症的感染，其中 1/4 發生或具有一定程度的耐藥性。 Gepotidacin 將被定位為治療失敗風險患者的口服選擇。

In September last year, to complement the development of our antimicrobial franchise, we announced a license agreement with Spero Therapeutics to commercialize tebipenem, a novel antibiotic in Phase III development for the treatment of complicated UTIs. There are around 3 billion complicated UTIs in the U.S. each year, and 40% of these infections are resistant to broad-spectrum oral antibiotics.

去年 9 月，為了補充我們抗菌特許經營權的發展，我們宣布與 Spero Therapeutics 達成許可協議，將替比培南商業化，這是一種處於 III 期開發階段的新型抗生素，用於治療複雜的 UTI。美國每年大約有 30 億例複雜的 UTI，其中 40% 的感染對廣譜口服抗生素具有耐藥性。

Tebipenem could be the first oral carbapenem approved for the treatment of complicated UTI reaching the market by 2026. Our goal is to develop 2 novel oral antibiotics that cover the spectrum of urinary tract infections and address increasing recurrence and community antimicrobials.

到 2026 年，替比培南可能是第一個獲准用於治療複雜性 UTI 的口服碳青黴烯類藥物。我們的目標是開發 2 種新型口服抗生素，涵蓋尿路感染的範圍，並解決日益增加的複發和社區抗菌藥物問題。

Next slide, please. This slide illustrates some of the pipeline news we anticipate over the next year or so. We expect 2023 to be a busy year across the portfolio. We look forward to presenting our RSV older adult vaccine as the forthcoming U.S. FDA VRBPAC meeting in March, followed by a U.S. FDA regulatory decision in early May. We also anticipate Phase III data from our invasive meningococcal vaccine in the first half. There are around 1.2 million cases of invasive meningococcal disease each year, and if successful, this vaccine would target the 5 most common serotypes in 1 product. As I mentioned earlier, we expect to present data from the gepotidacin Phase III program and data from the bepirovirsen Phase II trial B-TOGETHER around midyear.

請換下一張幻燈片。這張幻燈片說明了我們預計在未來一年左右的一些管道新聞。我們預計 2023 年將是整個投資組合忙碌的一年。我們期待在即將於 3 月舉行的美國 FDA VRBPAC 會議上展示我們的 RSV 老年人疫苗，隨後美國 FDA 將於 5 月初做出監管決定。我們還預計上半年我們的侵襲性腦膜炎球菌疫苗的 III 期數據。每年大約有 120 萬例侵襲性腦膜炎球菌疾病，如果成功，這種疫苗將針對 1 種產品中的 5 種最常見的血清型。正如我之前提到的，我們希望在年中左右提供來自 gepotidacin III 期項目的數據和來自 bepirovirsen II 期試驗 B-TOGETHER 的數據。

In oncology, momelotinib has been submitted with regulatory authorities, and we expect to hear from the U.S. FDA during the first half. We'll also present the Jemperli RUBY data at a medical conference later this year. Finally, we also anticipate regulatory decision from the U.S. FDA on daprodustat for the treatment of anemia of chronic kidney disease, with a decision from European regulators around midyear.

在腫瘤學方面，momelotinib 已提交給監管機構，我們希望在上半年收到美國 FDA 的意見。我們還將在今年晚些時候的醫學會議上展示 Jemperli RUBY 數據。最後，我們還預計美國 FDA 將就 daprodustat 治療慢性腎病貧血做出監管決定，歐洲監管機構將在年中左右做出決定。

I'll now hand over to Luke. Next slide, please.

我現在將交給盧克。請換下一張幻燈片。

Thanks, Tony. Please turn to Slide 16. In 2022, we delivered 13% sales growth or 10% excluding COVID Solutions, and we're proud to report that 10 products exceeded GBP 1 billion in sales for the year, including Shingrix, Trelegy, Nucala, Benlysta and Dovato. This is a great example of strong commercial execution. Benlysta remains the market leader with 85% of new patient starts in Q4, and we continue to see a strong growth globally in both SLE and lupus nephritis with only 25% buyer penetration in the U.S. Nucala continues to lead the IL-5 class across all major markets, and Nucala remains the first and only biologic approved for 4 esinophilic diseases with new indications driving growth and differentiation. And Xevudy delivered GBP 2.3 billion in sales, although based on the trajectory of the pandemic, we expect limited sales in 2023, and Deborah will comment on HIV shortly.

謝謝，托尼。請轉到幻燈片 16。2022 年，我們實現了 13% 的銷售額增長或 10%（不包括 COVID Solutions），我們很自豪地報告 10 種產品全年銷售額超過 10 億英鎊，包括 Shingrix、Trelegy、Nucala、Benlysta和多瓦托。這是強大的商業執行力的一個很好的例子。 Benlysta 仍然是市場領導者，在第四季度有 85% 的新患者開始，我們繼續看到全球 SLE 和狼瘡性腎炎的強勁增長，美國的買家滲透率僅為 25%。Nucala 繼續在所有 IL-5 類別中領先主要市場，Nucala 仍然是第一個也是唯一一個被批准用於 4 種嗜酸性粒細胞疾病的生物製劑，具有推動生長和分化的新適應症。 Xevudy 實現了 23 億英鎊的銷售額，儘管根據大流行的軌跡，我們預計 2023 年的銷售額有限，Deborah 將很快就 HIV 發表評論。

In oncology, sales were up 17% for the year, with label changes to BLENREP and Zejula in the U.S., we expect to see a short-term decline before oncology returns to growth in 2024. In General Medicines, Trelegy had an excellent year, up 32% versus last year, retaining leadership in key markets. This was also bolstered by the post-pandemic rebound of the antibiotic market globally and increased demand for Augmentin.

在腫瘤學領域，隨著美國 BLENREP 和 Zejula 標籤的變化，今年銷售額增長了 17%，我們預計在 2024 年腫瘤學恢復增長之前會出現短期下滑。在通用藥物領域，Trelegy 表現出色，與去年相比增長 32%，在主要市場保持領先地位。全球抗生素市場大流行後的反彈以及對 Augmentin 的需求增加也推動了這一點。

Turning to our Vaccine's performance on Slide 17. In 2022, Vaccines had a strong year, up 17%, excluding pandemic-adjuvant sales. This reflects strong commercial execution across the portfolio, including a record year for Shingrix and increased contributions from Bexsero in the U.S. with higher CDC demand and increased market share. Shingrix sales grew significantly across all regions, reflecting post pandemic rebound and new market launches through geographic expansion. The U.S. saw higher demand in both the retail and non-retail setting and favorable channel inventory movements, while ex U.S. delivered around GBP 1 billion in sales for the year. Shingrix has launched now in 9 markets in 2022 and is now available in 26 countries, and we expect to continue to expand our geographic footprint in line with our goal to be in 35 countries by 2024.

轉到我們的疫苗在幻燈片 17 上的表現。在 2022 年，疫苗表現強勁，增長了 17%，不包括流行病佐劑的銷售。這反映了整個產品組合的強大商業執行力，包括 Shingrix 創紀錄的一年以及 Bexsero 在美國的貢獻增加，CDC 需求增加，市場份額增加。 Shingrix 的銷售額在所有地區都顯著增長，反映出大流行後的反彈和通過地域擴張推出的新市場。美國在零售和非零售環境以及有利的渠道庫存變動方面都看到了更高的需求，而除美國外，該年度的銷售額約為 10 億英鎊。 Shingrix 現已於 2022 年在 9 個市場推出，目前在 26 個國家/地區有售，我們預計將繼續擴大我們的地理足跡，以實現我們到 2024 年進入 35 個國家/地區的目標。

Turning to Slide 18. Here, you can see that prioritization of R&D and commercial investment in Specialty Medicines and Vaccines, plus optimization of the General Medicine portfolio is delivering strong growth and drive our progress. Our '22 results demonstrate that our strategy is working, and we're delivering on the commitments we made at the investor update in 2021. And the data on the right-hand chart show this shift up from 7% to 42% today.

轉到幻燈片 18。在這裡，您可以看到對特殊藥物和疫苗的研發和商業投資的優先排序，以及對普通藥物產品組合的優化正在實現強勁增長並推動我們取得進步。我們的 22 年結果表明我們的戰略正在發揮作用，我們正在兌現我們在 2021 年投資者更新中做出的承諾。右側圖表上的數據顯示，這一轉變從 7% 上升到今天的 42%。

Looking ahead to 2023, for the Specialty portfolio, including the short-term impact of oncology, we expect sales in 2023 to increase mid- to high single-digit percent, excluding Xevudy. In General Medicines, we expect 2023 sales to decrease slightly and remain on track with our broadly stable sales outlook between 2021 and 2026; and in Vaccines, overall, we expect to increase mid-teens percent, excluding pandemic-adjuvant sales and expect to see Shingrix momentum continued with double-digit growth with another record year of sales.

展望 2023 年，對於專業產品組合，包括腫瘤學的短期影響，我們預計 2023 年的銷售額將增長中高個位數百分比，不包括 Xevudy。在普通藥品方面，我們預計 2023 年的銷售額將略有下降，並保持在我們 2021 年至 2026 年大致穩定的銷售前景的軌道上；在疫苗方面，總體而言，我們預計將增長 15% 左右，不包括流行病佐劑的銷售額，並預計 Shingrix 的勢頭將繼續保持兩位數的增長，銷售額再創歷史新高。

With that, let me now hand over to Deborah on Slide 19.

有了這個，讓我現在將幻燈片 19 上的 Deborah 交給 Deborah。

Thank you, Luke. Our HIV business delivered sales of GBP 5.7 billion in 2022, growing 21% in Q4 and 12% for the year with our U.S. and European businesses both reporting significant growth. We achieved a notable acceleration in our innovation sales, delivering GBP 2.5 billion, representing 43% of our portfolio for the year and 48% in the quarter, up from 29% in full year 2021.

謝謝你，盧克。我們的 HIV 業務在 2022 年實現了 57 億英鎊的銷售額，第四季度增長 21%，全年增長 12%，我們的美國和歐洲業務均實現了顯著增長。我們的創新銷售實現了顯著加速，實現了 25 億英鎊的銷售額，占我們全年投資組合的 43% 和本季度的 48%，高於 2021 年全年的 29%。

Our performance benefited from strong patient demand for our innovation HIV medicines, Dovato, Cabenuva, Juluca, Rukobia and Apretude, contributing 9 percentage points of growth. U.S. pricing favorability and year-end inventory build together contributed 4 percentage points of growth, which was partially offset by international.

我們的業績得益於患者對我們的創新 HIV 藥物 Dovato、Cabenuva、Juluca、Rukobia 和 Apretude 的強勁需求，貢獻了 9 個百分點的增長。美國定價優惠和年底庫存增加共同貢獻了 4 個百分點的增長，但被國際市場部分抵消了。

Sales of Dovato delivered GBP 438 million in the quarter and GBP 1.4 billion for the full year, and this medicine is now firmly on track to become our biggest selling HIV product. We see the opportunity for Dovato as being balanced globally with around 50% of the potential sales in the U.S. and the remainder split between Europe and the rest of the world.

Dovato 在本季度的銷售額為 4.38 億英鎊，全年銷售額為 14 億英鎊，該藥物現在有望成為我們最暢銷的 HIV 產品。我們認為 Dovato 的機會在全球範圍內實現平衡，其中約 50% 的潛在銷售額在美國，其餘部分在歐洲和世界其他地區分配。

Turning to our portfolio. Cabenuva is our first-in-class long-acting treatment regimen for HIV. Sales for the quarter were GBP 129 million and GBP 340 million for the full year, reflecting strong patient demand with high levels of market access and reimbursement across the U.S. and Europe.

轉向我們的投資組合。 Cabenuva 是我們一流的 HIV 長效治療方案。本季度的銷售額為 1.29 億英鎊，全年銷售額為 3.4 億英鎊，反映了美國和歐洲市場准入和報銷水平高的患者需求強勁。

Moving on to prevention. Apretude is the world's first long-acting injectable for the prevention of HIV dosed every 2 months. Launched in the U.S. in January 2022 Apretude delivered GBP 21 million of sales in the quarter and GBP 41 million in the full year. HIV prevention is an area of significant unmet need as current options are associated with stigma and adherence issues. Apretude addresses these challenges and has demonstrated superior efficacy over daily oral tablets.

繼續預防。 Apretude 是世界上第一個用於預防 HIV 的長效注射劑，每 2 個月注射一次。 Apretude 於 2022 年 1 月在美國推出，本季度銷售額為 2100 萬英鎊，全年銷售額為 4100 萬英鎊。艾滋病毒預防是一個嚴重未滿足需求的領域，因為當前的選擇與污名化和依從性問題有關。 Apretude 解決了這些挑戰，並證明了優於每日口服片劑的療效。

Looking ahead to 2023, we expect to see continued strong patient demand for our new HIV medicines. We expect the year-end inventory build to burn through the first half of 2023. We are confident of delivering mid-single-digit growth this year. We're excited by our pipeline focused on innovative long-acting regimens, which we believe illustrates our ability to maintain our leadership beyond dolutegravir. By the second half of the decade, we expect cabotegravir to increasingly replace dolutegravir as the foundational integrated inhibitor in our portfolio.

展望 2023 年，我們預計患者對我們新的 HIV 藥物的需求將持續強勁。我們預計年底庫存增加將持續到 2023 年上半年。我們有信心在今年實現中個位數增長。我們對專注於創新長效療法的產品線感到興奮，我們相信這說明我們有能力在多替拉韋之後保持領先地位。到本世紀下半葉，我們預計 cabotegravir 將越來越多地取代 dolutegravir 作為我們產品組合中的基礎綜合抑製劑。

We have 3 clear target medicine profiles: to provide the world's first self-administered long-acting regimen for treatment and to provide ultra long-acting regimen for treatment and prevention with dosing intervals of 3 months and longer. We are looking forward to presenting further data on our pipeline, including the SOLAR study, a head-to-head trial between Cabenuva and ViiV and data on N6LS, our broadly neutralizing antibody at CROI in Seattle later this month.

我們有3個明確的靶點藥物概況：提供全球首個自主給藥的長效治療方案和提供給藥間隔3個月及以上的超長效治療和預防方案。我們期待在我們的管道中提供更多數據，包括 SOLAR 研究、Cabenuva 和 ViiV 之間的頭對頭試驗以及 N6LS 的數據，我們本月晚些時候在西雅圖 CROI 的廣泛中和抗體。

Our Q4 results demonstrate continued progress against our ambition to achieve a 5-year mid-single-digit sales CAGR to 2026. By 2026, we estimate that long-acting regimens will be generating around GBP 2 billion, which equates to around 1/3 of HIV sales. The changing mix of our portfolio towards long-acting and the success of our pipeline offers the potential to significantly replace the revenue from dolutegravir post loss of exclusivity.

我們的第四季度業績表明，我們在實現到 2026 年實現 5 年中個位數銷售額複合年增長率的雄心方面取得了持續進展。到 2026 年，我們估計長效療法將產生約 20 億英鎊的收入，相當於約 1/3艾滋病毒銷售。我們的產品組合向長效藥物組合的變化以及我們管道的成功提供了顯著取代多替拉韋失去獨占權後的收入的潛力。

And with that, I will hand you over to Iain.

有了這個，我會把你交給伊恩。

Thank you, Deborah. As I cover the financials, references to growth are at constant exchange rates unless stated otherwise. As Luke and Deborah covered the main revenue drivers, I'll focus my comments on the income statement, including the main cost drivers, margins, cash flow and guidance for 2023.

謝謝你，黛博拉。在我介紹財務數據時，除非另有說明，否則提及的增長均採用固定匯率。由於 Luke 和 Deborah 介紹了主要的收入驅動因素，我將重點關注損益表，包括主要成本驅動因素、利潤率、現金流和 2023 年的指導。

Turning to Slide 21. This slide shows the bridge from total to adjusted results includes the effect of the successful consumer health care demerger in 2022. Total earnings per share were 371.4p, which earnings per share from discontinued operations were 260.6p. This primarily reflected the gain on the demerger and the gain on the retained stake in Haleon.

轉到幻燈片 21。這張幻燈片顯示了從總體結果到調整後結果的橋樑，包括 2022 年成功的消費者醫療保健分拆的影響。每股總收益為 371.4 便士，其中終止經營的每股收益為 260.6 便士。這主要反映了分拆的收益和 Haleon 保留股權的收益。

Turning now to continuing operations. For 2022, turnover was GBP 29.3 billion, up 13%, and adjusted operating profit was GBP 8.2 billion, up 14%. Total earnings per share were 110.8p, up 18%, while adjusted earnings per share were 139.7p, up 15%. The main adjusting items of note between total and adjusted results for continuing operations in the year were in transaction-related, which primarily reflected the contingent consideration liability movements, the majority of which related to foreign exchange and in divestments significantly than other, which reflected the upfront income received from Gilead in the first quarter as well as a fair value mark-to-market gain and the retained stake in Haleon.

現在轉向持續經營。 2022 年營業額為 293 億英鎊，增長 13%，調整後營業利潤為 82 億英鎊，增長 14%。每股總收益為 110.8 便士，上漲 18%，調整後每股收益為 139.7 便士，上漲 15%。年內持續經營業務總業績和調整後業績之間的主要調整項目與交易相關，主要反映或有對價負債變動，其中大部分與外匯有關，撤資顯著高於其他，反映了第一季度從 Gilead 收到的預付款以及按市值計算的公允價值收益和 Haleon 的保留股權。

Pandemic Solutions reduced growth of adjusted operating profit by approximately 3 percentage points and growth of adjusted earnings per share by around 3 points. The full year currency impact was a favorable 6% in sales and 12% in adjusted earnings per share.

Pandemic Solutions 將調整後營業利潤的增長降低了約 3 個百分點，並將調整後每股收益的增長降低了約 3 個百分點。全年的貨幣影響是銷售額增長 6%，調整後每股收益增長 12%。

Turning to Slide 22. The 2022 adjusted operating margin of 27.8% reflected an improvement versus last year. The positive margin dynamics reflected the sales growth with a favorable mix, excluding Xevudy, higher royalty income and favorable currency movements, which are a 1.2 percentage point benefit in the full year. These factors were offset by the impact of lower margin sales of Xevudy and commercial investment behind launches and key products. Overall adjusted operating profit grew 14%. COVID Solutions reduced adjusted operating profit growth by approximately 3 percentage points and adjusted operating margin excluding COVID Solutions, was approximately 1.3% higher constant exchange rates.

轉到幻燈片 22。2022 年調整後的營業利潤率為 27.8%，與去年相比有所改善。積極的利潤率動態反映了銷售增長和有利的組合（不包括 Xevudy）、更高的特許權使用費收入和有利的貨幣變動，全年收益為 1.2 個百分點。這些因素被 Xevudy 較低的利潤率銷售以及發布和關鍵產品背後的商業投資的影響所抵消。整體調整後營業利潤增長 14%。 COVID Solutions 將調整後的營業利潤增長降低了約 3 個百分點，不包括 COVID Solutions 的調整後營業利潤率比固定匯率高出約 1.3%。

Turning to key dynamics of the year. Within cost of goods sold, the increase primarily related to sales of lower margin Xevudy, which increased the cost of sales margin by around 2.5 percentage points, mainly reflecting the profit share pay away to biotechnology. Excluding Xevudy, cost of goods sold benefited from a favorable business mix with Specialty Medicines and Vaccines comprising 62% of commercial operations sales ex pandemic. So this mix benefit was partly offset by increased supply chain costs, including in commodity prices and in freight.

轉向今年的關鍵動態。在銷貨成本中，增長主要與利潤率較低的 Xevudy 的銷售有關，這使銷售利潤成本增加了約 2.5 個百分點，主要反映了支付給生物技術的利潤分成。不包括 Xevudy 在內，銷售成本受益於特殊藥物和疫苗的有利業務組合，佔大流行前商業運營銷售額的 62%。因此，這種混合收益部分被供應鏈成本增加所抵消，包括商品價格和運費。

SG&A increased the rate slightly above sales, which primarily reflected launch investments in Specialty Medicines and Vaccines. We're particularly focused on HIV and Shingrix to drive post-pandemic demand recovery and support market expansion. The SG&A growth also reflected an unfavorable comparison to a beneficial legal settlement in 2021. These factors were partly offset by continued delivery of restructuring benefits with around GBP 900 million of annualized savings to date from the separation preparation program and tight controlled ongoing costs.

SG&A 的增長率略高於銷售額，這主要反映了對特種藥品和疫苗的啟動投資。我們特別關注 HIV 和 Shingrix，以推動大流行後的需求復蘇並支持市場擴張。 SG&A 的增長也反映出與 2021 年有利的法律和解相比不利。這些因素部分被重組收益的持續交付所抵消，迄今為止，分離準備計劃每年節省約 9 億英鎊，並嚴格控制持續成本。

R&D spend grew 6%, with increased investment across several programs, particularly in vaccines, clinical development, including in our mRNA technology platforms and MAPS following the Affinivax acquisition, along with investments in early discovery programs. In Specialty Medicines, with assets like depemokimab and bepirovirsen and within oncology, there was an increased investment in our early-stage immuno-oncology assets and momelotinib following the Sierra Oncology acquisition. These increases were partly offset by the lapping of now completed late-stage clinical programs and reduced investment in COVID-19 assets relative to 2021. Royalties benefited from the Gavi contribution and higher sales of Gardasil. Again, it should be noted that our Gardasil royalty stream will cease at the end of 2023.

研發支出增長了 6%，增加了對多個項目的投資，特別是在疫苗、臨床開發方面，包括我們的 mRNA 技術平台和收購 Affinivax 後的 MAPS，以及對早期發現項目的投資。在擁有 depemokimab 和 bepirovirsen 等資產的專業藥物以及腫瘤學領域，在收購 Sierra Oncology 後，我們增加了對我們的早期免疫腫瘤學資產和 momelotinib 的投資。這些增長部分被現已完成的後期臨床項目的重疊和與 2021 年相比減少的 COVID-19資產投資所抵消。特許權使用費受益於 Gavi 的貢獻和 Gardasil 的更高銷售額。同樣，應該注意的是，我們的 Gardasil 版稅流將在 2023 年底停止。

Turning to Slide 23. Moving to bottom half of the P&L and highlight that net finance expense was higher, reflecting the net cost associated with the November sterling notes repurchased, higher interest on tax, partly offset by increased interest income due to higher interest rates and larger cash balances as a result of the consumer health care demerger. And the effective tax rate of 15.5% reflected the timing of settlements with various tax authorities, which was favorable versus the expectations set out of Q3.

轉到幻燈片 23。轉到損益表的下半部分並強調淨財務費用較高，反映了與回購 11 月英鎊票據相關的淨成本、較高的稅息，部分被利率較高和利息收入增加所抵消消費者醫療保健分拆導致現金餘額增加。 15.5% 的有效稅率反映了與各稅務機關結算的時間，這與第三季度的預期相比是有利的。

On the next slide, I'll cover cash flow. In 2022, we generated GBP 3.3 billion of free cash flow from continuing operations. Within free cash flow, cash generated from operations increased around GBP 700 million, up 10% to GBP 7.9 billion, with higher operating profit being the key driver, partly offset by other factors, which you can see on this slide.

在下一張幻燈片中，我將介紹現金流。 2022 年，我們從持續經營中產生了 33 億英鎊的自由現金流。在自由現金流中，運營產生的現金增加了約 7 億英鎊，增長 10% 至 79 億英鎊，營業利潤增加是主要驅動因素，部分被其他因素抵消，您可以在這張幻燈片上看到。

Below cash generated from operations, there were higher tax payments and lower proceeds from disposals along with higher CapEx, partly offset by reduced purchase of intangibles. In 2023, we expect cash generated from operations to be slightly lower, primarily due to the positive impact of the Gilead settlement in February 2022, partly offset by improved operating profit growth. We remain firmly on track with our medium-term outlook, driven by higher adjusted operating profit and working on improvements.

在運營產生的現金之下，納稅額增加、處置收益減少以及資本支出增加，部分被無形資產購買減少所抵消。 2023 年，我們預計運營產生的現金將略有下降，這主要是由於 2022 年 2 月吉利德和解的積極影響，部分被運營利潤增長的改善所抵消。在更高的調整後營業利潤和努力改進的推動下，我們仍然堅定地走在中期展望的正軌上。

Turning now to Slide 25 and guidance for 2023. We expect to build upon the step change in performance we delivered in '22. As a reminder, all of our guidance excludes the contribution from pandemic COVID-related solutions and references to growth at constant exchange rates. We expect sales to increase between 6% and 8%, and we expect adjusted operating profit to increase between 10% and 12%. This is influenced by expected cost dynamics where we expect cost of goods sold and expect to increase at rates slightly below sales, SG&A to grow broadly aligned to sales and for royalties to grow versus 22%.

現在轉向幻燈片 25 和 2023 年的指導。我們希望在 22 年實現的性能階躍變化的基礎上再接再厲。提醒一下，我們的所有指導均不包括大流行 COVID 相關解決方案的貢獻以及對按固定匯率增長的參考。我們預計銷售額將增長 6% 至 8%，我們預計調整後的營業利潤將增長 10% 至 12%。這受到預期成本動態的影響，我們預計銷售成本和預期增長率將略低於銷售額，SG&A 的增長與銷售額大致保持一致，而特許權使用費的增長率為 22%。

Below operating profit, net interest payable is expected to be between GBP 750 million and GBP 800 million and the effective tax rate is expected to be around 15%. In light of these dynamics, we expect adjusted earnings per share to increase between 12% and 15%. We do not expect any significant pandemic-related sales in 2023.

低於營業利潤，應付淨利息預計在 7.5 億至 8 億英鎊之間，有效稅率預計在 15% 左右。鑑於這些動態，我們預計調整後的每股收益將增長 12% 至 15%。我們預計 2023 年不會出現任何與大流行相關的重大銷售。

With regards to phasing of the year, due to phasing in 2022 and resulting comparators, we would expect operating profit growth to be lower in the first half of the year and higher in the second half, relative to full year expectations. This reflects strong comparisons in the first half, including stock build in ViiV and Shingrix U.S. channel inventory build in the first half of 2022. We would also expect SG&A to grow at a higher rate than sales, reflecting investments to support recent and anticipated launches. Q1 is expected to be a more challenging quarter in the ViiV stock building at the end of 2022. In the second half, we would expect the growth to be higher due to expected launches of new products, including RSV as well as momentum across existing product drivers.

關於今年的分階段，由於 2022 年的分階段和由此產生的比較，我們預計與全年預期相比，今年上半年營業利潤增長將較低，下半年將較高。這反映了上半年的強勁比較，包括 2022 年上半年 ViiV 的庫存增加和 Shingrix 美國渠道庫存增加。我們還預計 SG&A 的增長速度將高於銷售額，這反映了支持近期和預期發布的投資。預計到 2022 年底，第一季度將是 ViiV 庫存建設中更具挑戰性的一個季度。下半年，我們預計由於預計將推出包括 RSV 在內的新產品以及現有產品的勢頭，增長將會更高司機。

Regarding dividends to shareholders. We anticipate a 56.5p dividend per share aligned to our dividend policy and prior disclosure. We started 2020 with excellent momentum from a highly successful '22 and remain firmly on track to deliver our medium-term financial commitments.

關於股東分紅。我們預計每股 56.5 便士的股息符合我們的股息政策和之前的披露。我們以非常成功的 22 年的良好勢頭開始了 2020 年，並繼續堅定地履行我們的中期財務承諾。

And with that, I'll hand back to Emma.

有了這個，我會交還給艾瑪。

Thanks, Iain. Turning to Slide 27. We continue to be guided in this by our purpose: to unite science, technology to go ahead of disease together. Integral to this is running a responsible business, one which builds trust and reduces risk to deliver sustainable health impact at scale, shareholder returns and to support our people to thrive. To do so, we prioritize our resources to focus on the 6 material areas affected here. This quarter, our leadership and progress in Access were recognized once again as we top the Access to Medicines Index for the eighth consecutive time, and we continue to lead in innovation to address antimicrobial resistance.

謝謝，伊恩。轉到幻燈片 27。我們繼續以我們的宗旨為指導：聯合科學、技術共同戰勝疾病。對此不可或缺的是經營一家負責任的企業，該企業建立信任並降低風險，以大規模提供可持續的健康影響、股東回報並支持我們的員工茁壯成長。為此，我們優先將資源集中在受影響的 6 個物質領域。本季度，我們在獲取藥品方面的領導地位和進步再次得到認可，我們連續第八次在獲取藥品指數中名列前茅，並且我們繼續引領創新以解決抗菌素耐藥性問題。

Also, we announced an investment of GBP 100 million to help strengthen health systems in lower-income countries, along with our commitment to invest GBP 1 billion in global health innovation where it's needed, as evidenced by our progress with the new first-in-class candidate medicine for patients with tuberculosis.

此外，我們宣布投資 1 億英鎊以幫助加強低收入國家的衛生系統，同時我們承諾在需要的地方投資 10 億英鎊用於全球衛生創新，我們在新的首創類結核病患者的候選藥物。

Turning to Slide 28. So in closing, I do want to thank our people for delivering this tremendous performance, a landmark year for GSK as a newly focused global biopharma company with big ambitions. We are delivering a step change in performance, and we enter 2023 confident that we will keep delivering again this year for our medium-term outlook and with the momentum to sustain growth through this decade and beyond.

轉到幻燈片 28。最後，我要感謝我們的員工取得如此巨大的業績，對於 GSK 作為一家新近專注於雄心勃勃的全球生物製藥公司來說，這是具有里程碑意義的一年。我們正在實現業績的階梯式變化，我們有信心進入 2023 年，我們將在今年繼續實現我們的中期展望，並保持在這十年及以後保持增長的勢頭。

So with that, operator, the team is ready. So let's move into Q&A.

因此，操作員，團隊準備就緒。那麼讓我們進入問答環節。

(Operator Instructions) And the first question is coming from the line of Kerry Holford.

（操作員說明）第一個問題來自 Kerry Holford。

So my real focus on the overall feedback specifically about the patient cohort. So I wonder if you can just use the commercial opportunity you see within that 50 to 59 year old group, if we assume the Phase III data that you are going to publish later this year is positive and the vaccine is ultimately approved in that age group. Do you think an age set recommendation population is a realistic scenario? And I'd be interested to know whether your existing in terms of target for that asset that brought us GBP 3 billion excludes any potential sales in that younger cohort.

所以我真正關注的是整體反饋，特別是關於患者群體的反饋。所以我想知道你是否可以利用你在 50 到 59 歲人群中看到的商業機會，如果我們假設你將在今年晚些時候發布的 III 期數據是積極的並且疫苗最終在該年齡段獲得批准.您認為年齡組推薦人群是現實的場景嗎？而且我很想知道您現有的為我們帶來 30 億英鎊的資產的目標是否不包括年輕人群中的任何潛在銷售。

Thanks, Kerry. Well, I think we'll come straight to Luke on that one. Obviously, an asset we're very excited about a lot of opportunity here, but Luke.

謝謝，克里。好吧，我想我們會在那個問題上直接找盧克。顯然，我們對這裡的很多機會感到非常興奮，但盧克。

Thanks, Kerry. I mean, yes, it's in that immunocompromised population. It's a sizable population, but the primary benefit is from a contract negotiation point of view for the 2024 season because we'll be the only one with that profile and evidence in that group, which, along with older individuals is obviously -- bears a significant burden from RSV infection. The previous guidance we've given includes that study is the full life cycle program.

謝謝，克里。我的意思是，是的，它存在於免疫功能低下的人群中。這是一個相當大的人口，但主要的好處是從 2024 賽季的合同談判的角度來看，因為我們將是該群體中唯一具有這種形象和證據的人，與年長的人一起顯然 - 承擔RSV 感染的顯著負擔。我們之前給出的指導包括研究是完整的生命週期計劃。

The next question is coming from Peter Welford from Jefferies.

下一個問題來自 Jefferies 的 Peter Welford。

It's on the outlook for Vaccines, for mid-teens. I wonder if Luke could give us some idea in terms of the usual sort of update into the Shingrix doses and where we are with returns to inventory and in terms of burning through that, particularly, I guess, given as well, presumably we're back to a more normal seasonality, if you like, of Shingrix, presumably with the sort of flu season, if you like, towards the end of the year. And what have you assumed in that mid-teens for RSV in the outlook as well? Should we be assuming is any modest contribution? Or how should we think about mid-teens in the context of obviously this being the first potential year of RSV sales in the U.S.

這是針對青少年的疫苗前景。我想知道 Luke 是否可以就 Shingrix 劑量的常規更新以及我們的庫存回報率和消耗量方面給我們一些想法，特別是，我想，鑑於我們大概是回到 Shingrix 的更正常的季節性，如果你願意的話，大概是在年底的流感季節。在 RSV 的前景中，你在那個十幾歲的時候也有什麼假設？我們是否應該假設有任何適度的貢獻？或者，在顯然今年是 RSV 在美國銷售的第一個潛在年份的背景下，我們應該如何考慮青少年

All right. Great. So I think as Luke said, it's going to be -- and I'm going straight to him, but another record year of Shingrix expected with double-digit growth and obviously, the first season for RSV, but for a major contributor to growth for the years ahead. But do you want to give a bit more shape on Shingrix, Luke?

好的。偉大的。所以我認為正如 Luke 所說，這將是——我會直接去找他，但 Shingrix 預計又創紀錄的一年將實現兩位數的增長，顯然，這是 RSV 的第一個賽季，但對於增長的主要貢獻者未來幾年。但是你想給 Shingrix 多一點造型嗎，盧克？

Sure, Emma. So Peter, thanks. I'll give a sort of an overarching answer first and then give you more detail on the U.S. dynamics around stock levels, et cetera with Shingrix and then also incorporate RSV into that answer. So I mean, our strategy remains the same. I mean, we tried to decouple Shingrix from the flu season. And yes, there is still volume associated with that just with people coming into the pharmacy.

當然，艾瑪。彼得，謝謝。我將首先給出一個總體答案，然後為您提供有關美國庫存水平動態的更多詳細信息，以及 Shingrix 等，然後還將 RSV 納入該答案。所以我的意思是，我們的戰略保持不變。我的意思是，我們試圖將 Shingrix 與流感季節脫鉤。是的，仍然有與進入藥房的人相關的數量。

I think the Inflation Reduction Act in the U.S., taking away the co-pay in that 65-plus group will be helpful. We know from our data, around 8% of patients reject a Shingrix shot based on co-pay concerns. It's probably understated, but we'll -- because pharmacists may self-select into proposing that to patients, but we'll see that in time. I think for Europe and Japan, where really things are starting to move, we just had a record month in January in Germany. Things are moving in Italy and other European markets. And I think if you look at the rest of the world, as China starts to normalize, the potential for that over the next couple of years remains very, very sizable. And then ultimately, we've got the opportunity to go back and rechallenge these populations with a booster in the second half of this decade.

我認為美國的通貨膨脹減少法案取消了 65 歲以上人群的共付額，這將有所幫助。我們從數據中得知，大約 8% 的患者基於共付額問題拒絕注射 Shingrix。它可能被低估了，但我們會 - 因為藥劑師可能會自行選擇向患者提出建議，但我們會及時看到。我認為對於真正開始發生變化的歐洲和日本，我們剛剛在德國 1 月份創下了創紀錄的月份。意大利和其他歐洲市場的情況正在發生變化。而且我認為，如果你看看世界其他地區，隨著中國開始正常化，未來幾年這種情況的潛力仍然非常非常大。然後最終，我們有機會在本十年的下半年回過頭來用助推器重新挑戰這些人群。

In terms of short term now in the U.S., I mean, the retail-nonretail split has stabilized. It's about 53% retail, 47% nonretail in Q4. The growth is evenly balanced between retail and nonretail. Stock levels have -- they came down in Q4. They're very much within the normal range of 1.1% to 0.9%, so we ended the year at 0.9 levels in the U.S. Now in terms of RSV, I don't want to give too much color on RSV, but I think Pfizer has made statements around penetration similar to flu. We agree with that. I think this product is going to build over multiple years in the U.S. and then as we follow a similar strategy that we've done with Shingrix, which is maintaining price discipline and then expanding into Europe and rest of world over the next few years.

就美國的短期而言，我的意思是，零售與非零售的分裂已經穩定下來。第四季度零售約佔 53%，非零售佔 47%。零售和非零售之間的增長是均衡的。庫存水平已經 - 他們在第四季度下降了。它們非常處於 1.1% 到 0.9% 的正常範圍內，所以我們今年年底在美國達到 0.9 的水平。現在就 RSV 而言，我不想在 RSV 上給出太多顏色，但我認為輝瑞已就類似於流感的滲透發表聲明。我們同意這一點。我認為該產品將在美國建立多年，然後我們將遵循我們對 Shingrix 所做的類似戰略，即保持價格紀律，然後在未來幾年內擴展到歐洲和世界其他地區。

Thanks, Luke. I also like the fact that we published it. I think you said that we're 15% more likely to get Shingrix post-COVID as well.

謝謝，盧克。我也喜歡我們發布它的事實。我想你說過我們在 COVID 後獲得 Shingrix 的可能性也高 15%。

Yes. Yes, it's certainly observable.

是的。是的，這當然是可以觀察到的。

Next one is coming from Dominic Lunn from Credit Suisse.

下一篇來自瑞士信貸的 Dominic Lunn。

My question is on pricing. So if you look at the January list price rises for GSK and indeed the industry as a whole, price rises have been in line with the historic price rises. So -- and one could have expected price taking to be a bit stronger given the high levels of inflation. And it looks like there is still room to take further price throughout the year before you hit the limit imposed by the inflation price cap in Medicare as well. So how should we think about pricing through the rest of the year? Could we get maybe smaller, more frequent incremental price rises through the year?

我的問題是關於定價。因此，如果您查看 GSK 以及整個行業 1 月份的標價上漲，就會發現價格上漲與歷史價格上漲一致。因此 - 考慮到高通脹水平，人們本可以預期價格上漲會更強一些。而且看起來在達到醫療保險通貨膨脹價格上限所施加的限制之前，全年仍有進一步定價的空間。那麼我們應該如何考慮今年剩餘時間的定價呢？我們能否在一年中實現更小、更頻繁的增量價格上漲？

Thanks. So look, GSK has got a long track record of being very responsible around its pricing. Let's hear, and as you know, on a net basis over the last few years, I think would be even very slightly down and really thoughtful about how we take this all. But Luke and maybe Deborah, a comment, please.

謝謝。所以看，葛蘭素史克在定價方面有著非常負責任的長期記錄。讓我們聽聽，正如你所知，在過去幾年的淨基礎上，我認為我們會如何處理這一切，甚至會非常低落並且非常深思熟慮。請 Luke 和 Deborah 發表評論。

Yes, completely agree, Emma. We're playing the long game here. I think past patterns over the last 2 years are probably a good indicator of our behavior going forward.

是的，完全同意，艾瑪。我們在這裡打持久戰。我認為過去兩年的過去模式可能是我們未來行為的一個很好的指標。

And I would just -- obviously, I agree with what Luke said. I think the other thing that people should be giving some thought to is what's happening outside the U.S. So if you look at our HIV business, for example, and many others will be experiencing the same thing, we're seeing significant additional net price pressure from clawbacks and price cuts. So from a pricing perspective, I think we've priced fairly and appropriately and playing the long game in the U.S., and I think we need to be aware and very vigilant about what's happening outside of the U.S. in terms of economic challenges leading countries to put pressure on pricing.

很明顯，我同意 Luke 所說的。我認為人們應該考慮的另一件事是美國以外正在發生的事情。例如，如果你看一下我們的 HIV 業務，許多其他人也會遇到同樣的事情，我們會看到額外的淨價格壓力來自回扣和降價。因此，從定價的角度來看，我認為我們已經公平合理地定價並在美國打了一場持久戰，我認為我們需要了解並非常警惕美國以外正在發生的經濟挑戰導致各國對定價施加壓力。

Next question is coming from James Quigley from Morgan Stanley.

下一個問題來自摩根士丹利的 James Quigley。

I've got a question on HIV. So could you give us an idea of the amount of stocking that you saw in the fourth quarter and which of the key products were impacted clearly for the full year, Tivicay and Triumeq seem to fare better in the U.S. than the next U.S. So with those 2 products as well, what are you sort of assuming for next year in the guidance? And then can you also give us a bit more color on the dynamics for Cabenuva and Apretude in terms of take-up, patient attitudes, physician attitudes and how that's changing with greater experience and how you expect the growth curve to look for the 2 long-acting drugs next year?

我有一個關於艾滋病毒的問題。那麼您能否告訴我們您在第四季度看到的庫存量以及全年哪些主要產品受到明顯影響，Tivicay 和 Triumeq 在美國的表現似乎比下一個美國更好。還有 2 種產品，您對明年的指導有何假設？然後你能不能給我們更多關於 Cabenuva 和 Apretude 在接受、患者態度、醫生態度方面的動態的顏色，以及隨著經驗的增加如何變化，以及你如何期望增長曲線尋找 2 長-明年拍藥？

Brilliant. Okay. So let's talk about stocking. So we entered last year with about 3 days of stock, which was low. Normally, we exit each year with about 7 days of stock. So we entered this year with 3 days of stock, 2022, with 3 days of stock. We exited with 13 days of stock. So as you can see, there's been a material shift between where we started '22 and where we exited. If we assume that we're going to just have a normal 2023 and that there will be 7 days of stock in the channel at the end of the year, you can see that we've got 6 days to burn, and we believe that's going to burn in the first half of the year. So that's kind of the details on the stock evolution.

傑出的。好的。那麼讓我們來談談放養。所以我們進入去年時有大約 3 天的庫存，這很低。通常，我們每年退出大約 7 天的庫存。所以我們進入今年有 3 天的庫存，2022 年有 3 天的庫存。我們以 13 天的庫存退出。因此，正如您所看到的，在我們開始 22 年的地方和我們退出的地方之間發生了重大轉變。如果我們假設我們將有一個正常的 2023 年並且到年底渠道將有 7 天的庫存，您可以看到我們有 6 天可以燃燒，我們相信這是將在今年上半年燃燒。這就是股票演變的細節。

In terms of Tivicay and Triumeq, I mean we're seeing Tivicay and Triumeq at a relatively kind of steady evolution. Triumeq is declining quite significantly as it's cannibalized by Dovato but also competitors. Tivicay is pretty stable actually. It's declining, but obviously, it's the only second-generation integrase inhibitor that you can have as a stand-alone and not as part of a triple or a doublet. So we continue to see a strong and sustained business with Tivicay. Triumeq, we think that business will decline as better opportunities are now there for people living with HIV.

就 Tivicay 和 Triumeq 而言，我的意思是我們看到 Tivicay 和 Triumeq 處於相對穩定的發展階段。 Triumeq 正在大幅下滑，因為它被 Dovato 和競爭對手蠶食。 Tivicay 實際上非常穩定。它正在下降，但很明顯，它是唯一一種可以單獨使用而不是作為三聯體或雙聯體的一部分的第二代整合酶抑製劑。因此，我們繼續看到與 Tivicay 的強大和持續的業務。 Triumeq，我們認為業務將會下降，因為現在為 HIV 感染者提供了更好的機會。

In terms of Cabenuva, so we've seen really strong patient demand. We're seeing excellent execution from our commercial teams, which is broadening the prescriber base and deepening the number of prescriptions each physician is writing. And we're doing a lot of work in the environment to overcome some of the barriers that you see when you introduce an injectable into a new therapy area for the first time. And we're really happy about the progress we're making. The level of access is significant. And as I've said before, the quality is also really, really positive as well. So I think Cabenuva is doing really well.

就 Cabenuva 而言，我們看到了非常強烈的患者需求。我們看到我們的商業團隊出色的執行力，這正在擴大開處方者的基礎並加深每位醫生開出的處方數量。我們在環境方面做了大量工作，以克服您在首次將注射劑引入新治療領域時遇到的一些障礙。我們對正在取得的進展感到非常高興。訪問級別很重要。正如我之前所說，質量也非常非常積極。所以我認為 Cabenuva 做得很好。

Apretude was slower last year. As we said in the first year of any new medicine and particularly in injectable, it takes a while to secure access and get all the big accounts signed up, the specialty pharmacy signed up on the product. That is now in a very, very positive place, and we've got very strong ambitions for Apretude in 2023. And again, all the research we do in terms of physician and patient. We know that the demand is very strong for this product as it offers something very different to the other, and obviously, we've got superiority data. So I hope you take away from that a lot of ambition and optimism for our long-acting injectable portfolio.

去年 Apretude 比較慢。正如我們在任何新藥的第一年所說的那樣，特別是在註射劑方面，需要一段時間才能確保訪問安全並讓所有大客戶註冊，專業藥房註冊該產品。現在這是一個非常非常積極的地方，我們對 2023 年的 Apretude 有非常強烈的抱負。再一次，我們在醫生和病人方面所做的所有研究。我們知道對該產品的需求非常強勁，因為它提供了與其他產品截然不同的東西，而且顯然，我們有優勢數據。因此，我希望您對我們的長效注射產品組合抱有很大的抱負和樂觀情緒。

I think also, as Deb referred to in our comments, I mean, the overall momentum on 2DRs across the board, I think, is up to like 40% between Dovato and with long-acting of the business. That's why we've done what we said we'd do in the shift of the portfolio, and we completely expect to do, again -- to do so again through long-acting, as Deb said, with the profile of the business by '26, but also to continue to shift beyond that ahead of the patent challenge on dolutegravir. And that's what's so exciting about what's coming through in the next generation pipeline, which we'll give -- Deborah and team will give you more insight on the 18 months ahead.

我認為，正如 Deb 在我們的評論中提到的那樣，我的意思是，我認為，在 Dovato 和長期業務之間，2DR 的整體勢頭高達 40%。這就是為什麼我們已經按照我們所說的那樣在投資組合的轉變中做，我們完全希望再次這樣做 - 通過長效再次這樣做，正如 Deb 所說，通過業務概況'26，而且還要繼續超越 dolutegravir 的專利挑戰。這就是下一代管道中正在發生的事情的令人興奮的地方，我們將提供——黛博拉和團隊將為您提供關於未來 18 個月的更多見解。

We have a question coming from Andrew Baum from Citi.

花旗銀行的安德魯鮑姆向我們提出了一個問題。

Staying with Cabenuva and given the profitability of this product even with the profit share, it's obviously hugely important for GSK going forward. Could you just give us a little bit more information on the source of the switching to date? And by that, I mean, just in the U.S. market, how much from Medicare, how much from 340B, how much is there for inventory? I know it may not represent long-term what things look like and its dynamic, but I would be interested.

留在 Cabenuva 並考慮到該產品的盈利能力，即使有利潤分成，這對 GSK 的未來發展顯然非常重要。您能否就迄今為止的轉換來源提供更多信息？我的意思是，僅在美國市場，Medicare 有多少，340B 有多少，庫存有多少？我知道它可能不代表事物的長期樣子及其動態，但我會感興趣。

And then second, in relation to the new generation of cabotegravir line extensions, including the subcu, we're going to get data in '24. How long will it take, do you believe, to secure approval, assuming that you do PK/PD bioequivalence trial starting in '24? Should I be assuming '26, '27 by the time you hit the market?

其次，關於新一代 cabotegravir 產品線擴展，包括 subcu，我們將在 24 年獲得數據。假設您從 24 年開始進行 PK/PD 生物等效性試驗，您認為需要多長時間才能獲得批准？當你進入市場時，我應該假設'26，'27嗎？

Thanks, Andrew. So straight back to Deb. Just as a reminder for everyone, part of our portfolio shift strategy, which is evidence is working when you see that shift from 46% of the portfolio up to 2/3 and our confidence by '26 is getting to 3/4 towards vaccination -- Vaccines, sorry, and Specialty Medicines is so that we're continuing to drive leverage in the P&L and affording our ability to keep investing at the same time in R&D and in our launches, too. So as well as within HIV through the innovation as we talked to, but also on the broad GSK agenda, we're seeing an important area of focus there for us. Deb?

謝謝，安德魯。所以直接回到黛布。提醒大家，我們的投資組合轉變戰略的一部分，當你看到投資組合的比例從 46% 上升到 2/3 並且我們對疫苗接種的信心在 26 年達到 3/4 時，這就是證據。 - 疫苗，抱歉，專業藥物使我們能夠繼續推動損益的槓桿作用，並提供我們在研發和發布的同時繼續投資的能力。因此，除了在我們交談過的通過創新進行的 HIV 內部，而且在廣泛的 GSK 議程上，我們看到了我們關注的一個重要領域。德布？

So just to quickly cover your points, Andrew. So in terms of the source of business, there's 2 ways we look at this. So first of all, where are we getting the business from and I can confirm about 60% of our Cabenuva business from our competitors and about 40% from our own portfolio. Second point, which is around what segments of the market are we getting Cabenuva from.

所以，為了快速說明你的觀點，安德魯。因此，就業務來源而言，我們有兩種看待方式。所以首先，我們從哪裡獲得業務，我可以確認我們約 60% 的 Cabenuva 業務來自我們的競爭對手，約 40% 來自我們自己的投資組合。第二點，關於我們從哪些市場細分市場獲得 Cabenuva。

Actually, we've got really good coverage across all the payers and all the key accounts. So actually, there's the split that we see for Cabenuva is broadly in line with the split of the overall market, which, as you know, is 40% kind of commercial payer in HIV and 60% government. So there's no unique attribute to Cabenuva versus how the market normally plays out.

實際上，我們已經很好地覆蓋了所有付款人和所有主要客戶。所以實際上，我們看到的 Cabenuva 的分裂與整個市場的分裂大致一致，正如你所知，這是 40% 的 HIV 商業支付者和 60% 的政府。因此，與市場正常表現相比，Cabenuva 沒有獨特的屬性。

In terms of the pipeline, so there are 3 time lines that we've laid out in our business investor update. So we've talked about a self-administered treatment and a longer-acting prevention between '25 and '27. Then we've talked about a longer-acting treatment, so 3 months-plus after 2027 probably in the '27, '28 period. And then we've got, which we're very excited about, our third-generation integrase inhibitor, which will either be teamed with our capsid or with our bNAb , and that is where you've got the potential for 6 months plus in terms of gap between administration. And that's towards the end of the decade.

就管道而言，我們在商業投資者更新中列出了 3 個時間表。所以我們已經討論了 25 到 27 年間的自我管理治療和長效預防。然後我們討論了一種長效治療，所以 2027 年之後可能在 27、28 年期間超過 3 個月。然後我們得到了我們非常興奮的第三代整合酶抑製劑，它將與我們的衣殼或我們的 bNAb 組合，這就是你有 6 個月以上的潛力的地方行政方面的差距。那是在本世紀末。

So that's kind of what we've set out in the update that we gave. And we're still absolutely on track for that. Very excited about the future. And just to reiterate our shorter-term goal, we are very confident in our ability to deliver that GBP 2 billion of revenue in 2026, which is 1/3 of our overall business in HIV at that point.

這就是我們在更新中提出的內容。而且我們仍然完全走在正軌上。對未來感到非常興奮。重申一下我們的短期目標，我們對我們在 2026 年實現 20 億英鎊收入的能力非常有信心，這是我們當時在 HIV 領域整體業務的 1/3。

The next question is coming from Tim Anderson from Wolfe Research.

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

I have a question on COVID flu co-formulated vaccine. So Pfizer yesterday suggested the launch of a combo product in 2025, talked about it as a compelling durable offering. Does Glaxo see an opportunity here for itself? And what's the time line of launch for a similar product from Glaxo? And then if I can just sneak in one quick housekeeping question. Zejula, when do you expect mature overall survival data from the PRIMA trial in frontline ovarian?

我對 COVID 流感複合疫苗有疑問。因此，輝瑞昨天建議在 2025 年推出一種組合產品，並將其稱為一種引人注目的耐用產品。葛蘭素史克是否從中看到了機會？ Glaxo 推出類似產品的時間表是什麼時候？然後，如果我可以偷偷提出一個快速的內務問題。 Zejula，您預計 PRIMA 卵巢癌前線試驗何時會提供成熟的總體生存數據？

Right. Well, both of those to come to Tony. And just as I think what he did refer to in his remarks, obviously, we're pleased to see the data that's come through from our partners at CureVac, and the potential for doublets here is definitely interesting. And we'll update more on our actual specific plans, I think, later in the year. But Tony, I'm sure you want to add to that as well as the Zejula question.

正確的。好吧，他們兩個都來找托尼。正如我認為他在他的言論中確實提到的那樣，顯然，我們很高興看到來自我們合作夥伴 CureVac 的數據，這裡的雙胞胎潛力肯定很有趣。我認為，我們將在今年晚些時候更新更多關於我們實際具體計劃的信息。但是托尼，我確定你想補充這個以及 Zejula 問題。

Yes. Let me just build on the question about doublets. And I think I'd start with just giving you a sense of the exciting data that we're generating with our partner, particularly CureVac, in the context of establishing the opportunity for a therapeutic window between immunogenicity and reactogenicity. And in a doublet vaccine, particularly with regards to flu, for example, you can think about this as the majority loading of that doublet vaccine coming from components that are addressing flu. We very much see the opportunity in the second half of the decade associated with the high-dose flu market, where an 8-valent vaccine covering both hemagglutinin and neuraminidase antigens is really the opportunity at hand.

是的。讓我以關於雙胞胎的問題為基礎。我想我首先要讓你了解我們與我們的合作夥伴，特別是 CureVac 產生的令人興奮的數據，在為免疫原性和反應原性之間的治療窗口建立機會的背景下。在雙聯疫苗中，特別是關於流感，例如，你可以認為這是雙聯疫苗的大部分負載來自應對流感的成分。我們非常看好 20 世紀下半葉與高劑量流感市場相關的機會，其中涵蓋血凝素和神經氨酸酶抗原的 8 價疫苗確實是眼前的機會。

So let me just quickly address what we're seeing in these early monovalent data that gives us the opportunity for excitement. And that is in the flu vaccinations, you will have noted that in a comparator -- a monovalent comparator, we see immunogenicity at the lowest dose, which is consistent or better than that comparator and seroconversion, which is also better than the comparator. In our COVID studies, which have a slightly different comparative basis, we see reactogenicity, which is at the low end in terms of distribution of grades and severity at the highest doses involved. What that is doing for us on the back of monovalent construct is creating an opportunity for a window and therapeutic index that I think makes a valent flu plus COVID doublet a practical possibility. We're now accelerating studies from monovalency into multivalency in a Phase II study the aim of targeting a multivalent seasonal vaccine focused on 8-valent flu in the second half of the decade.

因此，讓我快速談談我們在這些早期單價數據中看到的內容，這些數據讓我們有機會興奮。那就是在流感疫苗接種中，你會注意到在比較器中——單價比較器，我們看到最低劑量的免疫原性，與比較器和血清轉化一致或更好，這也比比較器更好。在我們的 COVID 研究中，比較基礎略有不同，我們看到了反應原性，在所涉及的最高劑量下，反應原性在等級和嚴重程度的分佈方面處於低端。在單價結構的背後為我們所做的是為窗口和治療指數創造機會，我認為這使價流感加 COVID 雙聯體成為可能。我們現在正在加速 II 期研究中從單價到多價的研究，目標是在 20 世紀下半葉開發針對 8 價流感的多價季節性疫苗。

As far as PRIMA is concerned, look, obviously, this is an event-driven outcome study. So it's something that's going to -- I'm reluctant to give data on. We're not expecting OS data before 2024.

就 PRIMA 而言，顯然，這是一項事件驅動的結果研究。所以這將是——我不願意提供數據。我們預計 2024 年之前不會有操作系統數據。

The next question is coming from Graham Parry from Bank of America.

下一個問題來自美國銀行的 Graham Parry。

So it's going back to RSV vaccine. I think you sort of referred to this requiring a lot of education, obviously, having more than one player in the market can help there. We've also referred to probably a launch trajectory below Shingrix. I was just wondering if there's a lower bound analog for launch that you could point to that you would think is appropriate, whether it's pneumococcal vaccines or perhaps one of the older pediatric vaccines. And any thoughts you've got on the recent Moderna interim data and the level of competitive threat that you see from having 3 vaccines in the market just from a contracting and pricing point of view more than anything else.

所以它又回到了 RSV 疫苗。我想你有點提到這需要大量的教育，顯然，市場上有不止一個參與者可以幫助那裡。我們還提到了可能低於 Shingrix 的發射軌跡。我只是想知道是否有一個你認為合適的發射下限類似物，無論是肺炎球菌疫苗還是一種較老的兒科疫苗。以及你對最近的 Moderna 中期數據的任何想法，以及你從合同和定價的角度來看市場上有 3 種疫苗所帶來的競爭威脅程度。

Thanks. Luke?

謝謝。盧克？

Yes, Graham. I mean, I think lower bound pneumococcal, again, it's not a perfect comparator but I think that's a fair one. I think you'll get more information with the pricing being presented at the Feb ACIP by ourselves and Pfizer on the 23rd, 24th of February. Look, I think that having 3 companies there, you're definitely going to drive awareness and a more rapid uptake. So the pie will be larger but obviously shared 3 ways. Our expectation is that it will only be Pfizer and ourselves at the June ACIP and that remains the same.

是的，格雷厄姆。我的意思是，我認為下限肺炎球菌，它不是一個完美的比較器，但我認為這是一個公平的比較器。我認為你會在 2 月 23 日、24 日我們和輝瑞公司在 2 月 ACIP 上展示的定價中獲得更多信息。聽著，我認為那裡有 3 家公司，你肯定會提高知名度和更快的接受度。所以餡餅會更大，但顯然有 3 種方式。我們的期望是，在 6 月的 ACIP 上只有輝瑞和我們自己，而且保持不變。

I think from a strategy point of view, as always, you need to anchor in your own evidence base. And I think the 94% efficacy that we have in adults with comorbidity is impressive and the similar range that we have in the 70 to 79 year-old group who obviously bear the brunt of RSV infections. I mentioned earlier from Kerry's question, the 50 to 59 year population that will also have evidence of that for the 2024 cycle. So all of these things help contracting. And I think there's just 2 big variables that remain unknown.

我認為從戰略的角度來看，一如既往，你需要錨定自己的證據基礎。我認為我們在患有合併症的成年人中取得的 94% 的療效令人印象深刻，而且我們在 70 至 79 歲人群中的療效範圍相似，他們顯然首當其沖地受到 RSV 感染。我之前在 Kerry 的問題中提到過，50 到 59 歲的人口也將有 2024 年周期的證據。所以所有這些都有助於簽約。而且我認為只有 2 個大變量仍然未知。

One is the final label that people ultimately get. Again, we've only seen headline data at this point. And then secondly, ourselves and Pfizer are likely to have that second year of exposure data just before the June ACIP, and that's a variable that remains unfactored at this point. But net-net, I think it's still a very exciting opportunity. And what is striking is just the level of awareness and just the depth of the RSV infections that we've seen this year post-COVID.

一是人們最終得到的最終標籤。同樣，我們此時只看到了標題數據。其次，我們自己和輝瑞公司可能會在 6 月 ACIP 之前獲得第二年的暴露數據，這是一個目前仍未考慮的變量。但是 net-net，我認為這仍然是一個非常令人興奮的機會。令人震驚的是我們今年在 COVID 之後看到的意識水平和 RSV 感染的深度。

Exactly. And our co-admin on flu is another big umbrella to retail. That's where semi distribution will be here.

確切地。我們的流感聯合管理員是零售業的另一大保護傘。這就是半分佈將在這裡的地方。

You have a question coming from James Gordon from JPMorgan.

摩根大通的 James Gordon 向您提問。

James? James, are you there?

詹姆士？詹姆斯，你在嗎？

James Gordon from JPMorgan. Can you hear me now?

摩根大通的詹姆斯戈登。你能聽到我嗎？

Yes.

是的。

Yes, we can hear you, James.

是的，我們能聽到你的聲音，詹姆斯。

You've hear me. Brilliant. Lovely. Two questions, please, both on vaccines. One was on RSV. So just in terms of multiyear protection, based on what you've seen so far, have you seen things that are encouraging just in terms of the efficacies you've seen through the year that suggest you are likely to get multiyear protection? And if you do, is that something that would actually be upside to the share assumptions you already had? Or was multiyear protection somewhat baked into the projections you've already given for this vaccine? That was the first question, please.

你聽我說了。傑出的。迷人的。有兩個問題，都是關於疫苗的。一個是 RSV。因此，就多年保護而言，根據您目前所見，您是否看到了令人鼓舞的事情，僅就您在一年中所看到的功效而言，這表明您可能會獲得多年保護？如果你這樣做了，那是否真的會超出你已經擁有的股票假設？或者您已經對這種疫苗做出的預測中是否包含了多年保護？這是第一個問題，請。

And the second one was on Shingrix. So there was the potential need for a booster mentioned. What data would you actually need for that? Do you have some data that's already telling you when you think you might need revaccination? And would you have to do a study that actually showed a statistically significant benefit on symptoms from revaccination? Or would it be more just about antibody titers? Is there like a quicker route to get such a recommendation?

第二個是在 Shingrix 上。因此，可能需要提到助推器。您實際上需要什麼數據？當您認為您可能需要重新接種疫苗時，您是否有一些數據已經告訴您？您是否必須進行一項研究，實際顯示重新接種疫苗對症狀有統計學意義的顯著益處？還是僅僅與抗體滴度有關？有沒有更快的途徑來獲得這樣的推薦？

Right. Well, I'll give both of those to Tony. But just as a reminder on Shingrix, we launched it in 2018, I think. So -- or '17. So -- and we've got good data for 10 years. So the cohorts coming through, the boosting is more for later in the decade, as Luke alluded to. But definitely something that we'll look at. But Tony, do you want to respond on both the RSV durability and Shingrix.

正確的。好吧，我會把這些都給托尼。但正如關於 Shingrix 的提醒，我認為我們是在 2018 年推出的。所以 - 或者'17。所以 - 我們有 10 年的良好數據。因此，正如 Luke 所暗示的那樣，在這十年的後期，更多的是通過隊列來提升。但絕對是我們會看到的東西。但是托尼，你想對 RSV 耐用性和 Shingrix 做出回應嗎？

Yes, sure. So first of all, in terms of duration for RSV, obviously, we have solid coverage across single-season vaccine efficacy with our existing data package. And James, you may remember, we also have titers that are elevated above baseline as measured at the end of first year. As Luke indicated, we're planning -- and indeed the study was designed with this purpose in mind, to be able to bring second season data to ACIP in June. Obviously, that is depending on the dynamics of the second season. And so we'll be able to report more on that when we get to the June date. Can you just remind me -- in terms of was it incorporated, second season data was not incorporated in the baseline model, so it would be an upside. And then can you just -- sorry, what was the second question?

是的，當然。因此，首先，就 RSV 的持續時間而言，很明顯，我們現有的數據包對單季疫苗功效有可靠的覆蓋。詹姆斯，你可能還記得，我們也有在第一年年底測量的高於基線的效價。正如 Luke 所指出的，我們正在計劃——事實上，這項研究的設計就是為了這個目的，以便能夠在 6 月份將第二季的數據帶到 ACIP。顯然，這取決於第二季的動態。因此，當我們到達 6 月的日期時，我們將能夠就此進行更多報告。你能不能提醒我——就是否合併而言，第二季數據沒有合併到基線模型中，所以這將是一個好處。然後你能不能-- 抱歉，第二個問題是什麼？

Shingrix.

新格里克斯。

Shingrix booster, yes. Okay. So obviously, we have 10-year data from Study 049 and that shows outstanding duration of protection. That's cumulative vaccine efficacy of greater than 82% over the 6- to 10-year period of follow-up, 89% vaccine efficacy over the 10-year period. Study 049 was designed to continue to generate data in order to answer the booster question. Remember that the vaccine was launched in 2018. And so we're reaching a point now with 10 years subsequent to that, we'll be looking to later in the decade.

Shingrix 助推器，是的。好的。很明顯，我們有來自 Study 049 的 10 年數據，顯示出出色的保護持續時間。在 6 到 10 年的隨訪期內，累積疫苗效力超過 82%，在 10 年期間疫苗效力達到 89%。 Study 049 旨在繼續生成數據以回答助推器問題。請記住，該疫苗是在 2018 年推出的。因此我們現在已經達到了 10 年後的一個點，我們將在這十年的晚些時候期待。

It's reasonable to expect that we will see some waning in vaccine efficacy associated with an aging population. But to your point, James, we're also engaging in ongoing conversations with the regulators to understand what the design of a study required to show the need of a booster would look like and for whom. But I don't want to go into any greater detail about that at this stage.

可以合理地預期，我們會看到與人口老齡化相關的疫苗效力有所減弱。但就你的觀點而言，James，我們還在與監管機構進行持續對話，以了解顯示加強劑需求所需的研究設計是什麼樣的，以及為誰設計的。但我不想在現階段對此進行更詳細的介紹。

Great. Thank you. So maybe one or two more questions and we'll try and speak through those. Next one, please.

偉大的。謝謝你。所以也許還有一兩個問題，我們將嘗試通過這些問題進行討論。下一個，請。

Next one is coming from Emily Field from Barclays.

下一個來自巴克萊銀行的 Emily Field。

The level of detail provided on the ongoing Zantac litigation release was very helpful and particularly following the MDL update in December. And the time lines on California were also helpful. I was just wondering if perhaps you could put in context how you're thinking about the rest of the state cases and just for -- on our side, it's been tough to follow kind of what follows the dower standard and what doesn't. But just outside of California, if there's any states where cases could be moving to trial in the near future that we should be mindful of?

正在進行的 Zantac 訴訟發布所提供的詳細程度非常有幫助，尤其是在 12 月的 MDL 更新之後。加利福尼亞州的時間表也很有幫助。我只是想知道您是否可以將您對其他州案件的看法放在上下文中，只是為了 - 在我們這邊，很難遵循什麼遵循嫁妝標準，什麼不遵循。但就在加利福尼亞州以外，是否有任何州的案件可能會在不久的將來進入審判階段，我們應該注意這些州？

Right. Thanks, Emily. Obviously, we were delighted with the outcome in December. We've got some things to navigate through this year. But Iain, perhaps you could update on the different state situation?

正確的。謝謝，艾米麗。顯然，我們對 12 月份的結果感到滿意。今年我們有一些事情要解決。但是伊恩，也許你可以更新不同州的情況？

Yes, absolutely. Emily. So obviously, MDL was incredibly impactful. That took out the equation, 46,000 claims within the suits filed at the federal level. So I'm delighted with that decision, as Emma said. You reflect on the bulk of claims in State Court, they sit in Delaware with more than 70,000. And although it's clearly for the courts and Delaware to decide there is a pattern of behavior where they tended to follow federal precedent in that regard. So that is probably an encouraging indicator.

是的，一點沒錯。艾米麗。很明顯，MDL 具有令人難以置信的影響力。這去掉了等式，在聯邦一級提起的訴訟中有 46,000 項索賠。正如 Emma 所說，我對這個決定感到很高興。你想想州法院的大部分索賠，他們在特拉華州審理了 70,000 多起案件。儘管法院和特拉華州顯然可以做出決定，但在這方面他們傾向於遵循聯邦先例的行為模式。所以這可能是一個令人鼓舞的指標。

Then across the other states, we've got a little bit less than 6,000 claims out there, which about 3,000 are in California and the rest are spread across sort of half a dozen other states. We've got 4 bell weathers that will -- that we expect to take place in California this year, the first of which will kick off a little bit later this month or early March. The Sargon hearing for that trial has actually been pushed back another week to the 16th of February as the judge reflects on input from both plaintiff and defense attorney.

然後在其他州，我們有不到 6,000 份索賠，其中大約 3,000 份在加利福尼亞州，其餘分佈在其他六個州。我們有 4 個好天氣——我們預計今年將在加利福尼亞發生，第一個將在本月晚些時候或 3 月初開始。由於法官考慮了原告和辯護律師的意見，該審判的 Sargon 聽證會實際上已推遲一周至 2 月 16 日。

So look, again, the really important thing here, the MDL decision, the diverse decision was incredibly helpful. It was informed by the strength of the epidemiological independent studies of which that are now 13, the consensus of which is there's no causality between the consumption of ranitidine in any form of cancer. And it's clear from Judge Rosenberg's decision that was the significant factor in informing our decisions. So we'll continue to defend vigorously and first up or a couple of trials in California, we'll keep you posted.

所以，再看一次，這裡真正重要的事情是 MDL 決定，多樣化的決定非常有幫助。它是根據流行病學獨立研究的力量獲悉的，這些研究現在已有 13 項，其共識是服用雷尼替丁與任何形式的癌症之間沒有因果關係。從羅森博格法官的決定中可以清楚地看出，這是影響我們做出決定的重要因素。因此，我們將繼續大力捍衛，首先在加利福尼亞州進行或進行幾次試驗，我們會及時通知您。

Right. And then last question, please.

正確的。最後一個問題，請。

Our final question comes from Simon Baker from Redburn.

我們的最後一個問題來自 Redburn 的 Simon Baker。

I promise I'll be quick. A question on BLENREP. Tony, back in November on the Q3 call, you mentioned that there was ongoing analysis involving soluble BCMA as a prognostic indicator. I just wonder if you could give us any update on the findings from that. And related to BLENREP, I see DREAMM-7 and DREAMM-8 have moved from H1 into H2. Is that shifting here for event-driven studies or is there anything else we should be aware of?

我保證我會很快的。關於 BLENREP 的問題。托尼，早在 11 月的第三季度電話會議上，您提到正在進行的分析涉及將可溶性 BCMA 作為預後指標。我只是想知道您是否可以向我們提供有關調查結果的最新信息。與 BLENREP 相關，我看到 DREAMM-7 和 DREAMM-8 已從 H1 移至 H2。對於事件驅動研究，這種情況是否會發生變化，或者還有什麼我們應該注意的嗎？

You cut out just to the second part of that question, but I think it was 1 of the implications in the first half, second half on 7 and 8. But -- sorry, for you, Tony.

你只問了那個問題的第二部分，但我認為這是上半場的影響之一，下半場是 7 和 8。但是 - 對不起，托尼。

Yes. Look. So Simon, the analysis that we discussed in terms of soluble BCMA and other markers that might explain the crossover that we see in DREAMM-3 is still ongoing. As far as DREAMM-7 and DREAMM-8 outcomes are concerned, we're now targeting a more complete picture of those. And if I remind you, these are 2 studies that are looking at BLENREP in combination versus standard of care in contrast to DREAMM-3, which was BLENREP and monotherapy. We're expecting to be able to provide a deeper update on those at the end of the year. And not much more to say at this stage, Simon. The analysis is ongoing. We'll bring this, when I've got a clearer picture.

是的。看。所以西蒙，我們根據可溶性 BCMA 和其他可能解釋我們在 DREAMM-3 中看到的交叉的標記討論的分析仍在進行中。就 DREAMM-7 和 DREAMM-8 結果而言，我們現在的目標是更全面地了解這些結果。如果我提醒你，這兩項研究正在研究 BLENREP 與護理標準的結合，與 DREAMM-3 相比，後者是 BLENREP 和單一療法。我們希望能夠在年底提供更深入的更新。西蒙，現階段無需多說。分析正在進行中。我們會帶來這個，當我有一個更清晰的畫面。

Thanks. Great. Well, thank you, everyone. I hope this has been an efficient call for you. We're delighted with the momentum and progress in the business. We look into 2023 with confidence and do so also for our medium-term outlook and beyond. We look forward to staying connected and keeping you updated in coming quarters and along the way. Thanks very much. Bye.

謝謝。偉大的。嗯，謝謝大家。我希望這對您來說是一個有效的呼籲。我們對業務的勢頭和進展感到高興。我們滿懷信心地展望 2023 年，並為我們的中期及以後的展望也這樣做。我們期待與您保持聯繫，並在未來幾個季度和整個過程中為您提供最新信息。非常感謝。再見。