葛蘭素史克 (GSK) 2021 Q4 法說會逐字稿

Good day, and welcome, everyone, ladies and gentlemen, to the analyst call for GSK fourth quarter 2021 results. I will now hand you over to Nick Stone, Head of Global Investor Relations, who will introduce today's session. Please proceed.

美好的一天，歡迎大家，女士們，先生們，分析師呼籲 GSK 2021 年第四季度業績。我現在將把您交給全球投資者關係主管尼克斯通，他將介紹今天的會議。請繼續。

Thank you, operator. Hello, everyone. This is Nick, obviously, the operator's just mentioned. Welcome to our full year and Q4 2021 conference call and webcast for investors and analysts. The presentation was posted to gsk.com and it was also sent out by e-mail to our distribution list earlier today.

謝謝你，接線員。大家好。這是尼克，顯然，剛才提到的接線員。歡迎來到我們面向投資者和分析師的全年和 2021 年第四季度電話會議和網絡直播。該演示文稿已發佈到 gsk.com，並且今天早些時候還通過電子郵件發送到我們的分發列表。

Please turn to Slide 2. This is the usual safe harbor statement, and we'll be making comments using constant exchange rates, or CER, unless otherwise stated.

請轉到幻燈片 2。這是通常的安全港聲明，除非另有說明，否則我們將使用恆定匯率或 CER 發表評論。

Please turn to Slide 3. This is today's schedule. We'll plan to cover all aspects of our full year results. The presentation will last around 35 minutes to maximize the opportunity for questions. (Operator Instructions) Today, our speakers are Emma Walmsley, Luke Miels, Deborah Waterhouse, Brian McNamara, Iain Mackay and Hal Barron. The Q&A portion of the call will be joined by Roger Connor and David Redfern.

請轉到幻燈片 3。這是今天的日程安排。我們將計劃涵蓋全年業績的各個方面。演講將持續約 35 分鐘，以最大限度地增加提問的機會。 （操作員說明）今天，我們的演講者是 Emma Walmsley、Luke Miels、Deborah Waterhouse、Brian McNamara、Iain Mackay 和 Hal Barron。電話的問答部分將由羅傑康納和大衛雷德芬加入。

And with that, I will now hand the call over to Emma. Please turn to Slide 4.

有了這個，我現在將把電話交給艾瑪。請轉到幻燈片 4。

Thanks, Nick, and a very warm welcome to everyone.

謝謝，尼克，並熱烈歡迎大家。

I am delighted to announce our 2021 full year results. They demonstrate strong financial performance and continued progress against our strategic priorities. For the full year, sales increased 5% and adjusted EPS increased 9%. Excluding the contribution from COVID solutions, we exceeded our raised guidance with adjusted EPS stable for the full year.

我很高興地宣布我們的 2021 年全年業績。它們展示了強勁的財務業績和在我們的戰略重點方面的持續進展。全年銷售額增長 5%，調整後每股收益增長 9%。不包括 COVID 解決方案的貢獻，我們超過了我們上調的指引，全年調整後的每股收益穩定。

Sales growth was driven by first-class commercial execution and strong uptake of new products. Pharma delivered 10% growth, New and Specialty Medicines growing 26%, double-digit sales in Immuno-inflammation, Respiratory and Oncology, together with sales from Xevudy for COVID-19, all drove this performance. Vaccine sales increased 2%, and Consumer Healthcare finished the year with 4% growth overall, notably accelerating again in the fourth quarter with sales up 11%.

銷售增長是由一流的商業執行和新產品的強勁吸收推動的。製藥公司實現了 10% 的增長，新藥和特殊藥物增長了 26%，免疫炎症、呼吸和腫瘤學的兩位數銷售額，以及 Xevudy 用於 COVID-19 的銷售額，都推動了這一業績。疫苗銷售額增長了 2%，消費者保健品以 4% 的整體增長結束了這一年，在第四季度再次顯著加速，銷售額增長了 11%。

Alongside this, we increased investments for key R&D pipeline programs, expanded support for new and ongoing launches and maintained a strong focus on cost optimization. This has also reflected in adjusted operating profit growth, which increased 9% for the full year.

除此之外，我們增加了對關鍵研發管道項目的投資，擴大了對新的和正在進行的發布的支持，並保持對成本優化的高度關注。這也反映在調整後的營業利潤增長上，全年增長 9%。

We see these results as very encouraging and a demonstration of the accelerating momentum we now have at GSK. As we said, 2022 marks a step change in growth for the company and is underscored by the guidance for new GSK, the biopharma business we're giving today of 5% to 7% sales growth and 12% to 14% adjusted operating profit growth of CER. This includes the anticipated benefit of Biktarvy-related royalties, but excludes any contribution from pandemic solutions, and Iain will provide more detail on this and our overall financial performance in his section.

我們認為這些結果非常令人鼓舞，並證明了我們現在在 GSK 擁有的加速勢頭。正如我們所說，2022 年標誌著公司增長的一個階段性變化，新 GSK 的指導強調了這一點，我們今天提供的生物製藥業務銷售額增長 5% 至 7%，調整後的營業利潤增長 12% 至 14%的 CER。這包括 Biktarvy 相關特許權使用費的預期收益，但不包括大流行解決方案的任何貢獻，Iain 將在他的部分中提供有關這方面和我們整體財務業績的更多細節。

Turning to Slide 6. 2021 was a year of excellent progress across all 3 of our long-term strategic priorities. In innovation, we delivered 3 major product approvals: Jemperli for endometrial cancer, Xevudy for COVID-19 and Apretude, our new long-acting medicine for HIV prevention. We also presented positive Phase III data for daprodustat, a potential best-in-class medicine for treating anemia of chronic kidney disease, and we expect to file this new and exciting medicine with regulators in the first half of 2022.

轉到幻燈片 6。2021 年是我們在所有 3 個長期戰略重點方面取得出色進展的一年。在創新方面，我們提供了 3 個主要產品批准：用於子宮內膜癌的 Jemperli、用於 COVID-19 的 Xevudy 和 Apretude，我們用於預防 HIV 的新型長效藥物。我們還提供了 daprodustat 的積極 III 期數據，這是一種治療慢性腎病貧血的潛在同類最佳藥物，我們預計將在 2022 年上半年向監管機構提交這種令人興奮的新藥物。

These new medicines are at the forefront of an exciting high-value pipeline we continue to build across prevention and treatment of disease through organic and inorganic delivery. We now have a pipeline of 21 vaccines and 43 medicines, 22 of which are in pivotal studies. And this year, we anticipate data readouts on up to 7 of the 11 new vaccines and medicines we've identified as key future growth drivers. This includes our RSV vaccine for older adults in the first half of 2022 and several new potential specialty treatments, including those for rheumatoid arthritis, cancer and hepatitis B.

這些新藥處於令人興奮的高價值管道的最前沿，我們將繼續通過有機和無機遞送來預防和治療疾病。我們現在擁有 21 種疫苗和 43 種藥物，其中 22 種處於關鍵研究階段。今年，我們預計 11 種新疫苗和藥物中的 7 種將公佈數據，這些疫苗和藥物被我們確定為未來的關鍵增長動力。這包括我們在 2022 年上半年為老年人提供的 RSV 疫苗和幾種新的潛在專業治療方法，包括類風濕性關節炎、癌症和乙型肝炎的治療方法。

In performance, our decision to prioritize investments in commercial execution to Specialty Medicines and Vaccines is evident in our improving sales growth. Shingrix sales clearly reflected the adverse impact of COVID-19 last year, particularly in the U.S., but we exceeded our expectations, highlighted at Q3, to deliver sales of GBP 1.7 billion. And this year, we do expect to see strong recovery growth and Luke will detail on this in a moment.

在業績方面，我們將商業執行優先投資於特種藥物和疫苗的決定在我們不斷提高的銷售增長中顯而易見。 Shingrix 的銷售額清楚地反映了去年 COVID-19 的不利影響，尤其是在美國，但我們超出了我們在第三季度強調的預期，實現了 17 億英鎊的銷售額。今年，我們確實預計會看到強勁的複蘇增長，Luke 稍後會詳細介紹這一點。

And lastly, on trust, we continue to maintain sector leadership in ESG with our #1 ranking in the Dow Jones Sustainability Index and our long-standing leadership in the Access to Medicines Index. Looking ahead, we also aim to deliver ambitious environmental commitments with targets of net zero on carbon and net positive on nature by 2030, and we're also making good progress on diversity and inclusion. ESG will continue to be an integral part of new GSK strategy and investment case.

最後，基於信任，我們繼續保持在 ESG 領域的領先地位，在道瓊斯可持續發展指數中排名第一，在藥品獲取指數中長期處於領先地位。展望未來，我們還致力於實現雄心勃勃的環境承諾，到 2030 年實現碳淨零排放和自然淨正排放目標，我們也在多樣性和包容性方面取得良好進展。 ESG 將繼續成為 GSK 新戰略和投資案例不可或缺的一部分。

And turning to Slide 7. 2022 sees the biggest change in GSK's recent corporate history with the creation of a new unique world leader dedicated to consumer effective in the middle of this year. This will be the culmination of a series of progressive strategic moves successfully executed over the last few years to build significant value and a new consumer health care company.

轉到幻燈片 7。 2022 年，葛蘭素史克 (GSK) 近期的企業歷史發生了最大的變化，今年年中創建了一個致力於消費者效益的新的獨特的世界領導者。這將是過去幾年成功執行的一系列漸進式戰略舉措的高潮，以建立重要的價值和新的消費者醫療保健公司。

We're now in full countdown mode to demerger. And by doing so, our aim is to unlock the potential of both GSK and consumer health, to strengthen GSK's balance sheet and to maximize value for all our shareholders. As a new stand-alone company, the Consumer Healthcare business is a compelling prospect. It has an outstanding brand portfolio, and we'll be a world leader in consumer health. For prospective investors, it will offer a highly attractive financial profile of above category sales growth, sustainable margin expansion and high stable cash generation.

我們現在處於分拆的完全倒計時模式。通過這樣做，我們的目標是釋放葛蘭素史克和消費者健康的潛力，加強葛蘭素史克的資產負債表，並為所有股東實現價值最大化。作為一家新的獨立公司，消費者保健業務前景廣闊。它擁有出色的品牌組合，我們將成為消費者健康領域的世界領導者。對於潛在投資者而言，它將提供上述類別銷售增長、可持續利潤率擴張和高穩定現金產生的極具吸引力的財務狀況。

It will have a fantastic leadership team, led by CEO Designate Brian McNamara and the Board with best-in-class international consumer sector experience as is already evident with the recent appointment of Sir Dave Lewis as Chairman Designate. We're going to provide a lot more detail on this business at our Capital Markets event later this month, and Brian will give you more on this shortly.

它將擁有一支出色的領導團隊，由候任首席執行官布萊恩麥克納馬拉和董事會領導，他們擁有一流的國際消費行業經驗，最近任命戴夫劉易斯爵士為候任主席已經證明了這一點。我們將在本月晚些時候的資本市場活動中提供有關此業務的更多詳細信息，Brian 將很快為您提供更多信息。

For new GSK, as we've previously shared, we've set a new purpose and new ambitions for growth. Our purpose is to unite science, talent and technology to get ahead of disease together to deliver scale, human health impact, improved returns to shareholders and to be a company where outstanding people thrive. This is reflected in the growth commitments and ambition we set out in our investor update in June last year. These represent a significant step-change in delivery for GSK. And as I said earlier, start now and are reflected in the guidance we're giving today and the exciting R&D catalysts ahead.

對於新葛蘭素史克，正如我們之前分享的那樣，我們設定了新的目標和新的增長雄心。我們的目標是聯合科學、人才和技術，共同戰勝疾病，帶來規模效應、人類健康影響、提高股東回報，並成為一家讓優秀人才茁壯成長的公司。這反映在我們在去年 6 月的投資者更新中設定的增長承諾和雄心。這些代表了葛蘭素史克在交付方面的重大轉變。正如我之前所說，從現在開始，並反映在我們今天提供的指導和未來令人興奮的研發催化劑中。

Before closing, I would like to say a very big thank you to the more than 94,000 GSK people who helped them to deliver our 2021 performance and the momentum they have built as we head into this landmark year. So let me now hand over to this team, who will take you through more of the detail.

在結束之前，我要非常感謝 94,000 多名葛蘭素史克員工，他們幫助他們實現了 2021 年的業績，以及他們在我們進入這一具有里程碑意義的一年時所建立的勢頭。所以現在讓我交給這個團隊，他們會帶你了解更多細節。

Luke, first of all, over to you.

盧克，首先，交給你。

Thanks, Emma. Please turn to Slide 9.

謝謝，艾瑪。請轉到幻燈片 9。

Let me start with New and Specialty, where we made remarkable progress driven by excellent commercial execution. Excluding Xevudy, we delivered 14% sales growth for the year and 10% in Q4, maintaining our double-digit track record. I'm incredibly proud to report that 2 of our assets exceeded GBP 1 billion in sales for the first time, Trelegy and Nucala. And as you've seen, we were able to respond quickly to the strong demand for Xevudy, delivering close to GBP 1 billion in sales of this crucial COVID treatment. Trelegy had a fantastic year despite growing competition, and our unique dual indication in COPD and asthma continues to drive higher demand in the U.S. and Japan.

讓我從 New and Specialty 開始，在出色的商業執行力的推動下，我們取得了顯著進展。不包括 Xevudy，我們全年實現了 14% 的銷售額增長，第四季度實現了 10% 的增長，保持了兩位數的業績記錄。我非常自豪地報告說，我們的兩項資產的銷售額首次超過 10 億英鎊，分別是 Trelegy 和 Nucala。正如您所見，我們能夠快速響應對 Xevudy 的強勁需求，為這種關鍵的 COVID 治療提供了近 10 億英鎊的銷售額。儘管競爭日益激烈，但 Trelegy 還是度過了美好的一年，我們獨特的 COPD 和哮喘雙重適應症繼續推動美國和日本的更高需求。

We've also seen very positive trends for our launch in China, where the single inhaler therapy class is growing rapidly and we are winning share in Tier 1 and Tier 2 cities.

我們也看到了我們在中國推出的非常積極的趨勢，單一吸入器治療類別正在迅速增長，我們在 1 線和 2 線城市贏得了份額。

For Nucala, sales were up 22%, and it remains the leading IL-5 for EOS-driven disease as a key market. We're pleased to see that our robust approach to life cycle innovation is driving incremental growth opportunities with the launch of 3 new indications: EGPA, HES and nasal polyps in Europe. Benlysta also benefited from label expansion with sales up 29% as we reach more new patients with lupus nephritis. And against the backdrop of COVID, we continue to see the importance of having a subcut formulation available for at-home use. And as expected, with competitors entering the market, we've seen an overall increase in biologic use, benefiting Benlysta as the leader.

Nucala 的銷售額增長了 22%，並且作為關鍵市場，它仍然是 EOS 驅動疾病的領先 IL-5。我們很高興看到我們強大的生命週期創新方法正在推動增量增長機會，推出 3 種新適應症：EGPA、HES 和歐洲鼻息肉。隨著我們接觸到更多狼瘡性腎炎新患者，Benlysta 還受益於標籤擴張，銷售額增長了 29%。在 COVID 的背景下，我們繼續看到提供可在家使用的細分配方的重要性。正如預期的那樣，隨著競爭對手的進入，我們看到生物製品的使用總體上有所增加，這使 Benlysta 成為領導者。

In Oncology, we continue to make steady progress. BLENREP remains the only off-the-shelf anti-BCMA therapy, and we've expanded our presence for 13 markets. In the U.S., we're driving use in the community setting where most multiple myeloma patients are treated. And we're working to reach new physicians as prescribing experience improved perceptions of corneal adverse events management.

在腫瘤學方面，我們繼續穩步前進。 BLNREP 仍然是唯一的現成抗 BCMA 療法，我們已經將我們的業務擴展到 13 個市場。在美國，我們正在推動在大多數多發性骨髓瘤患者接受治療的社區環境中使用。我們正在努力接觸新的醫生，因為處方經驗改善了對角膜不良事件管理的認識。

Closing with Zejula, COVID continues to impact the ovarian cancer market with diagnosed systems of bulking surgeries still below pre-pandemic levels. Despite the constrained market, Zejula delivered its strongest quarter of sales to date, and we continue to perform exceptionally well in market share terms with 1 and 2 new patients receiving a part being prescribed Zejula. So a very strong year for New and Specialty, and we expect to grow Specialty sales by around 10% in 2022, even with Trelegy moving into the new General Medicines area. And this is before we include the expected contribution from Xevudy.

隨著 Zejula 的結束，COVID 繼續影響卵巢癌市場，診斷出的膨脹手術系統仍低於大流行前的水平。儘管市場受到限制，但 Zejula 實現了迄今為止最強勁的季度銷售額，我們繼續在市場份額方面表現出色，有 1 名和 2 名新患者接受了 Zejula 的處方。所以對於 New and Specialty 來說是非常強勁的一年，我們預計到 2022 年 Specialty 銷售額將增長約 10%，即使 Trelegy 進入新的通用藥物領域。這是在我們包括 Xevudy 的預期貢獻之前。

Please turn to Slide 10. Moving to Vaccines. Full year sales increased by 2%, but decreased by 5% excluding pandemic sales. The overall performance demonstrated the impact on several of our vaccines at COVID, most impacted with Shingrix, where sales were down 9% in the year, which was slightly better than the outlook we indicated at the 9-month stage. Based on the encouraging early momentum we're seeing, we continue to anticipate a strong sales recovery in 2022.

請轉到幻燈片 10。轉到疫苗。全年銷售額增長了 2%，但不包括大流行的銷售額則下降了 5%。整體表現證明了對我們在 COVID 中的幾種疫苗的影響，其中受 Shingrix 影響最大，該公司今年的銷售額下降了 9%，略好於我們在 9 個月階段表示的前景。基於我們看到的令人鼓舞的早期勢頭，我們繼續預計 2022 年銷售將強勁復甦。

Since Q2 2021, Shingrix has delivered strong sequential growth, reflecting an improvement in trends in the U.S. including solid demand in the non-retail channel as well as contributions from new European launches and recovery of demand in Germany. We expect this momentum to continue in 2022 despite Omicron short-term impact. We continue to launch in new markets supported by our unconstructed supply position, and we believe there is a significant pent-up demand in the U.S.

自 2021 年第二季度以來，Shingrix 實現了強勁的環比增長，這反映了美國趨勢的改善，包括非零售渠道的強勁需求以及歐洲新品發布和德國需求復甦的貢獻。儘管有 Omicron 的短期影響，我們預計這一勢頭將在 2022 年繼續。我們繼續在未構建供應狀況的支持下在新市場推出，我們相信美國存在大量被壓抑的需求。

Consequently, we continue to expect Shingrix to deliver strong double-digit sales growth in 2022 with record annual sales. This will be a crucial driver of the expected low teens sales growth of vaccines here, including pandemic solutions. Looking further ahead, by 2024, we expect Shingrix to be available in 35 markets, representing nearly 90% of the global vaccine market, underscoring our ambition to double Shingrix revenues by 2026.

因此，我們繼續預計 Shingrix 將在 2022 年實現強勁的兩位數銷售增長，年銷售額創歷史新高。這將是這裡預期的青少年疫苗銷售增長的關鍵驅動力，包括流行病解決方案。展望未來，到 2024 年，我們預計 Shingrix 將在 35 個市場上市，佔全球疫苗市場的近 90%，這突顯了我們到 2026 年將 Shingrix 收入翻番的雄心。

Let me now hand over to Deborah on Slide 11.

現在讓我在幻燈片 11 上交給黛博拉。

Thank you, Luke.

謝謝你，盧克。

Our goal is to remain innovation leaders in HIV, achieve a mid-single-digit sales CAGR to 2026, and digest the loss of exclusivity of dolutegravir at the end of the decade through the changing mix of our portfolio and the success of our pipeline. Our Q4 and full year results demonstrate positive momentum towards delivering on these objectives.

我們的目標是保持 HIV 領域的創新領導者地位，到 2026 年實現中個位數的銷售複合年增長率，並通過我們產品組合的變化和我們管道的成功在十年末消化 dolutegravir 排他性的損失。我們的第四季度和全年業績顯示出實現這些目標的積極勢頭。

Sales grew 3%, both for Q4 and for the year. Within this, we achieved a noticeable acceleration in our innovation sales, which now stands at 34% of our portfolio and all regions reported growth. This acceleration in growth results from strong commercial execution behind our 2-drug regimens and Dovato in particular. Sales of Dovato more than doubled to GBP 787 million and are fast approaching 20% of the total HIV sales. Dolutegravir-based regimens now hold the #1 position in the share of the switch market across the U.S. and Europe. Based on this strong momentum, we believe Dovato is on track to deliver GBP 1 billion of sales in 2022 with further significant growth potential beyond.

第四季度和全年的銷售額均增長了 3%。在此過程中，我們的創新銷售實現了顯著加速，目前占我們產品組合的 34%，所有地區都報告了增長。這種增長的加速是由於我們的 2 種藥物方案，尤其是 Dovato 背後強大的商業執行力。 Dovato 的銷售額翻了一番多，達到 7.87 億英鎊，並迅速接近 HIV 總銷售額的 20%。基於 Dolutegravir 的方案現在在美國和歐洲的轉換市場份額中排名第一。基於這一強勁勢頭，我們認為 Dovato 有望在 2022 年實現 10 億英鎊的銷售額，並具有進一步的顯著增長潛力。

Please turn to Slide 12. Turning to our injectable portfolio. Cabenuva is our first-in-class, long-acting regimen for the treatment of HIV for which we received FDA approval last week for every 2-month dosing. As with any new class of medicine, sales of Cabenuva will take time to build and the COVID environment is constraining switch activity, particularly where a patient needs to visit a physician's office. Nevertheless, over 4,500 people living with HIV are already taking Cabenuva/Vocabria/Rekambys and the outlook for this important new medicine is strong brand recognition and market access exceeding 80%.

請轉到幻燈片 12。轉到我們的注射產品組合。 Cabenuva 是我們用於治療 HIV 的一流長效方案，我們上週獲得 FDA 批准，每 2 個月給藥一次。與任何新型藥物一樣， Cabenuva 的銷售需要時間來建立，而 COVID 環境正在限制轉換活動，尤其是在患者需要就診的情況下。儘管如此，超過 4,500 名 HIV 感染者已經在服用 Cabenuva/Vocabria/Rekambys，這種重要的新藥的前景是強大的品牌認知度和超過 80% 的市場准入。

Moving on to prevention. We ended 2021 on a high with the FDA approval of Apretude, the world's first long-acting injectable for the prevention of HIV, dosed every 2 months. HIV prevention is a huge unmet need as current medical options are associated with stigma and adherence issues. Apretude not only addresses these concerns, but it has demonstrated superior efficacy over daily oral tablets.

繼續預防。隨著 FDA 批准 Apretude ，我們以高水平結束了 2021 年，這是世界上第一個用於預防 HIV 的長效注射劑，每 2 個月給藥一次。 HIV 預防是一個巨大的未滿足需求，因為當前的醫療選擇與污名和依從性問題有關。 Apretude 不僅解決了這些問題，而且顯示出優於每日口服片劑的功效。

As a new paradigm, we need to educate physicians, patients and payers. So this year, our focus is on building awareness and access for Apretude. The early signs are encouraging with positive feedback from patients and prescribers and with political will supportive of HIV prevention. Consequently, we remain confident that Apretude will deliver significant benefits to patients in the years ahead as well as significant commercial value beginning in 2023.

作為一種新的範式，我們需要對醫生、患者和付款人進行教育。因此，今年，我們的重點是建立 Apretude 的知名度和訪問權限。早期跡象令人鼓舞，患者和處方者的積極反饋以及支持艾滋病毒預防的政治意願。因此，我們仍然相信 Apretude 將在未來幾年為患者帶來顯著的益處，並從 2023 年開始具有顯著的商業價值。

And with that, I will hand over to Brian, and we will move on to Slide 13.

有了這個，我將交給布賴恩，我們將繼續進行幻燈片 13。

Thanks, Deborah.

謝謝，黛博拉。

Now turning to Consumer Healthcare. Sales for the full year, excluding brands divested under review, increased by 4% at constant exchange rates despite a negative 1% impact of COVID on cold and flu sales, building on the 4% growth we delivered in 2020. International grew 9%, with emerging markets performing particularly well, including China, Middle East and Africa growing double digits. U.S. sales increased 2% and Europe was broadly stable with both regions building momentum through the year.

現在轉向消費者保健。儘管在 2020 年實現了 4% 的增長基礎上，COVID 對感冒和流感銷售產生了 1% 的負面影響，但不包括正在審查中的被剝離品牌，全年銷售額仍增長 4%。國際增長 9%，新興市場表現尤其出色，包括中國、中東和非洲，增長兩位數。美國銷售額增長 2%，歐洲總體穩定，這兩個地區全年增長勢頭良好。

Q4 growth was strong, up 11% at constant exchange rates albeit against a weaker comparator of 1% growth in 2020, with all categories performing well. Cold and flu sales rebounded in Q4 with European sales above 2019, and U.S. sales only slightly below.

第四季度增長強勁，按固定匯率計算增長 11%，儘管相對於 2020 年 1% 的增長較弱，所有類別均表現良好。第四季度感冒和流感銷量反彈，歐洲銷量高於 2019 年，美國銷量僅略低於 2019 年。

From a category perspective for the full year, oral health sales increased 5%, with broad-based growth in key markets, reflecting brand strength, strong execution and successful innovation. Pain relief grew high single digits. This was primarily driven by Panadol, which benefited from seasonal demand in the second half of the year. Voltaren delivered mid-single-digit growth despite the expected introduction of U.S. private label earlier in the year.

從全年品類來看，口腔保健品銷售額增長 5%，主要市場實現廣泛增長，體現了品牌實力、強大的執行力和成功的創新。疼痛緩解增長了個位數。這主要是由 Panadol 推動的，它受益於下半年的季節性需求。儘管預期在今年早些時候引入美國自有品牌，Voltaren 仍實現了中個位數的增長。

Vitamins, Minerals and Supplements grew 4%, continuing the momentum on a very strong year-over-year comparator. Centrum growth in the second half was particularly strong due to increased capacity and retailer stocking. Respiratory declined 1%, with strong growth in allergy offset by a mid-single-digit decline of our cold and flu products. Q4 rebounded, delivering 40% growth due to a return of a more typical cold and flu demand, although it fell just short of offsetting the unprecedented market declines in Q1.

維生素、礦物質和補充劑增長 4%，繼續保持強勁的同比增長勢頭。由於產能增加和零售商庫存增加，Centrum 下半年的增長尤為強勁。呼吸系統下降了 1%，過敏的強勁增長被我們的感冒和流感產品的中個位數下降所抵消。由於更典型的感冒和流感需求的回歸，第四季度出現反彈，實現了 40% 的增長，儘管它的下降不足以抵消第一季度前所未有的市場下滑。

Digestive health and other sales were up mid-single digits with broad-based growth across skin, digestive health and smokers health. On e-commerce, year-to-date sales grew in the high 20% range and is now 8% of sales with good growth in key regions such as China. Our ongoing investment in digital capabilities continue to position us well for growth in this vital channel.

消化健康和其他銷售額增長了中個位數，皮膚、消化健康和吸煙者健康的基礎廣泛增長。在電子商務方面，年初至今的銷售額增長了 20% 的高位，現在佔銷售額的 8%，在中國等關鍵地區增長良好。我們對數字能力的持續投資繼續為我們在這一重要渠道的增長做好準備。

We've also delivered strong margin progression for the year of 200 basis points at constant exchange rates, while at the same time, increasing investment in our brands. Operational efficiencies on top of synergies, along with pricing, have more than offset the impact of divestments and inflation in the year.

我們還在固定匯率下實現了 200 個基點的強勁利潤率增長，同時增加了對我們品牌的投資。協同效應之上的運營效率以及定價已經抵消了當年撤資和通貨膨脹的影響。

Overall, looking at sales growth over the last 2 years, we've delivered a CAGR of over 4% despite net COVID headwinds. We're able to successfully capitalize on tailwinds created by increased vitamin and mineral supplement demand. However, these were more than offset by the decline in respiratory as a result of the historically low cold and flu season.

總體而言，縱觀過去 2 年的銷售增長，儘管面臨 COVID 的淨逆風，我們的複合年增長率仍超過 4%。我們能夠成功地利用維生素和礦物質補充劑需求增加帶來的順風。然而，這些都被歷史上感冒和流感低季導致的呼吸系統下降所抵消。

This clearly demonstrates the strength and breadth of our portfolio and the capabilities we've built through the 2 most significant transactions in the industry, coupled with extensive portfolio rationalization. This positions us to deliver sustained market outperformance, with a 4% to 6% medium-term annual sales outlook.

這清楚地表明了我們投資組合的實力和廣度，以及我們通過業內最重要的兩項交易以及廣泛的投資組合合理化所建立的能力。這使我們能夠提供持續的市場表現，中期年度銷售前景為 4% 至 6%。

Please turn to Slide 14. With regards to the upcoming separation, I'm delighted that Dave Lewis was recently appointed as Chair Designate and my executive leadership team has now been announced. I hope you will join us at our Capital Markets Day, which will take place virtually on February 28. We will lay out our strategic priorities, key growth drivers and detailed financial information. The team and I will share both the global and regional overview, including our innovation, digital and operational capabilities as well as our capital allocation priorities as a newly listed company. Most importantly, we will set out how we will deliver the growth, category outperformance and attractive sustainable returns that we are confident this business can achieve in the medium term.

請轉到幻燈片 14。關於即將到來的離職，我很高興 Dave Lewis 最近被任命為候任主席，我的執行領導團隊現已宣布。我希望您能加入我們的資本市場日，該日將在 2 月 28 日舉行。我們將列出我們的戰略重點、主要增長動力和詳細的財務信息。我和團隊將分享全球和區域概況，包括我們的創新、數字和運營能力，以及我們作為一家新上市公司的資本配置優先事項。最重要的是，我們將闡述我們將如何實現我們相信該業務可以在中期實現的增長、類別卓越表現和有吸引力的可持續回報。

With that, I'll hand it over to Iain. Please turn to page -- Slide 15.

有了這個，我會把它交給伊恩。請翻到第 15 頁。

Thanks, Brian. As I cover the financials, references to growth are at constant exchange rates unless stated.

謝謝，布賴恩。在我介紹財務數據時，除非另有說明，否則對增長的參考均以恆定匯率計算。

On Slide 16, there's a summary of the group's results for the full year 2021 and I'll focus my comments on the full year performance. Turnover was GBP 34.1 billion, up 5%, an adjusted operating profit was GBP 8.8 billion, up 9%. Total earnings per share were 87.6p, down 13%, while adjusted earnings per share was 113.2p, up 9%. Pandemic solutions contributed approximately 9 points of growth in adjusted earnings per share. On currency, there was a headwind of 5% in sales and 11% in adjusted earnings per share, in particular, due to the strengthening of sterling against the U.S. dollar relative to 2020.

在幻燈片 16 上，有該集團 2021 年全年業績的摘要，我將把我的評論集中在全年業績上。營業額為 341 億英鎊，增長 5%，調整後的營業利潤為 88 億英鎊，增長 9%。每股總收益為 87.6 便士，下降 13%，而調整後的每股收益為 113.2 便士，增長 9%。大流行解決方案為調整後的每股收益貢獻了大約 9 個百分點的增長。在貨幣方面，銷售額和調整後每股收益分別下降了 5% 和 11%，特別是由於相對於 2020 年英鎊兌美元走強。

Turning to the next slide. This slide summarizes the reconciliation of our total to adjusted results. The main adjusting items of note for the year were in disposals and other, which primarily reflected profits across several divestments, including the gain on disposal of rights to royalty stream for cabozantinib in Q1, the gain on disposal of the cephalosporin business in Q4 and a significant positive revaluation of deferred tax assets in the U.K. resulting from the Q2 enactment of the 2021 U.K. Finance Bill. And finally, in transaction related, the main factor was the movement on the ViiV CCL, which included the impact of the settlement with Gilead.

轉到下一張幻燈片。這張幻燈片總結了我們的總數與調整後結果的對賬。本年度主要調整項目為處置及其他，主要反映多項剝離的利潤，包括第一季度卡博替尼的特許權使用費處置收益、第四季度頭孢菌素業務處置收益和由於 2021 年英國財政法案的第二季度頒布，英國的遞延所得稅資產出現了顯著的正值重估。最後，在交易相關方面，主要因素是 ViiV CCL 的走勢，其中包括與 Gilead 和解的影響。

My comments from here onwards were adjusted results unless stated otherwise. Turning to Slide 18. Key drivers of revenues and profits for the group in 2021 compared to 2020 are set out here. Revenues grew 5% overall. Revenues from our COVID solutions contributed around 4 percentage points of that growth. Positive operating leverage from higher sales in the year was supported by continued focus on cost control and the benefits and synergies resulting from restructuring across the group, with SG&A down 1%. This included favorable legal settlements compared to increased legal costs in 2020, which primarily impacted Q1 and one-off benefits in pensions and insurance in Q4.

除非另有說明，否則我從這裡開始的評論都是調整後的結果。轉到幻燈片 18。與 2020 年相比，該集團在 2021 年的收入和利潤的主要驅動因素如下所述。收入總體增長了 5%。我們 COVID 解決方案的收入貢獻了大約 4 個百分點的增長。持續關注成本控制以及整個集團重組帶來的效益和協同效應支持了本年度較高銷售額帶來的積極經營槓桿，SG&A 下降了 1%。與 2020 年增加的法律費用相比，這包括有利的法律和解，這主要影響了第一季度以及第四季度養老金和保險的一次性福利。

Alongside these benefits, we continue to prioritize investing in our pipeline and R&D expenditures increased by 8%. This resulted in an adjusted operating profit increase of 9%, with pandemic solutions contributing 7 percentage points of that growth. The full year margin was 25.8% and 90 basis points higher than 2020 at constant exchange rates.

除了這些好處，我們繼續優先投資我們的管道，研發支出增加了 8%。這導致調整後的營業利潤增長了 9%，其中流行病解決方案貢獻了 7 個百分點的增長。按固定匯率計算，全年利潤率為 25.8%，比 2020 年高 90 個基點。

Turning to Slide 19. Moving to the bottom half of the P&L and highlight that the effective tax rate of 17.5% was aligned with expectations and that interest expense of GBP 753 million was slightly lower than expected, primarily due to favorable foreign exchange.

轉到幻燈片 19。轉到損益表的下半部分，並強調 17.5% 的有效稅率與預期一致，7.53 億英鎊的利息支出略低於預期，主要是由於有利的外匯。

Next, I'll briefly cover free cash flow for the year before going into more detail on the financials of each business. On Slide 20, in 2021, we generated GBP 4.4 billion of free cash flow. This was a step-down versus 2020 and consistent with our outlook given in February last year. The positive factors of increased adjusted operating profit at CER and lower dividends to noncontrolling interests were more than offset by increased purchases of intangible assets, including our collaborations with Alector and iTeos from Q3, reduced proceeds following completion of the Consumer Brands disposal program, adverse timing of returns and rebates compared to 2020 and adverse exchange impacts.

接下來，我將簡要介紹這一年的自由現金流，然後再詳細介紹每家企業的財務狀況。在幻燈片 20 中，我們在 2021 年產生了 44 億英鎊的自由現金流。這與 2020 年相比有所下降，與我們去年 2 月給出的展望一致。 CER 調整後營業利潤增加和非控股權益股息減少的積極因素被無形資產購買的增加所抵消，包括我們從第三季度開始與 Alector 和 iTeos 的合作、完成消費者品牌處置計劃後的收益減少、不利的時機與 2020 年相比的回報和回扣以及不利的匯率影響。

Net cash generated from operations for the group was GBP 8 billion, and we expect to share comparators for new GSK cash flow later in the first half. In 2022, we expect cash generated from operations for new GSK on a like-for-like basis to be higher than 2021 as a result of the Gilead settlement and increased adjusted operating profit. This will be partly offset by lower cash generated from lower-margin COVID solutions and headwinds related to the phasing of payments in 2021 and continued generics impact on the U.S. respiratory portfolio.

集團運營產生的淨現金為 80 億英鎊，我們預計將在上半年晚些時候分享新的 GSK 現金流的比較。由於吉利德和解和調整後的營業利潤增加，我們預計 2022 年新葛蘭素史克的運營產生的現金將高於 2021 年。這將被利潤率較低的 COVID 解決方案產生的現金減少以及與 2021 年分階段付款相關的不利因素以及仿製藥對美國呼吸系統產品組合的持續影響所部分抵消。

Turning to performance of the Pharma business on Slide 21. Overall, Pharmaceutical revenues grew 10%, driven by strong growth in New and Specialty Medicines, favorable U.S. return on rebate adjustments and sales of Xevudy, which contributed 6 percentage points of growth. But within this 10% growth, established Pharma sales decreased 6% in 2021, which was slightly better than expected.

在幻燈片 21 上轉向製藥業務的表現。總體而言，製藥收入增長了 10%，這得益於新藥和特種藥物的強勁增長、有利的美國回扣調整回報和 Xevudy 的銷售，這貢獻了 6 個百分點的增長。但在這 10% 的增長中，2021 年成熟的醫藥銷售額下降了 6%，略好於預期。

The Pharma operating margin was 26.4% for 2021. The increase in profit margin primarily reflected the positive operating leverage from the increased sales, including favorable pricing in IRR, continued tight cost control and restructuring benefits. This was partly offset by continued investment in R&D and HIV product launches.

2021 年製藥公司的營業利潤率為 26.4%。利潤率的增長主要反映了銷售額增加帶來的積極經營槓桿，包括內部收益率的有利定價、持續嚴格的成本控制和重組收益。這部分被對研發和 HIV 產品發布的持續投資所抵消。

Turning to Slide 22. Overall, vaccine sales grew (inaudible). Excluding pandemic adjuvant revenue, sales decreased 5%, primarily driven by Shingrix dynamics, which Luke has described. We continue to be very confident in the demand for our vaccines. Notably, during 2022, we expect Shingrix to deliver record sales with strong double-digit growth.

轉到幻燈片 22。總體而言，疫苗銷售增長（聽不清）。不包括大流行佐劑收入，銷售額下降了 5%，主要是由 Luke 所描述的 Shingrix 動態驅動。我們對疫苗的需求仍然非常有信心。值得注意的是，在 2022 年，我們預計 Shingrix 將以兩位數的強勁增長實現創紀錄的銷售額。

The operating margin was 33.3%. The decrease in operating profit and margin primarily reflected higher supply chain costs resulting from lower demand. This was accompanied by an increased R&D investment of 34% as we progressed our RSV and meningitis development programs and invested in our mRNA platform. Higher royalty income and beneficial mix from pandemic adjuvant sales partly offset these factors. Q4 sales were down 7%, reflecting a tough comparison in 2020 due to strong Shingrix sales.

營業利潤率為33.3%。營業利潤和利潤率的下降主要反映了需求下降導致供應鏈成本上升。隨著我們推進 RSV 和腦膜炎開發計劃並投資於我們的 mRNA 平台，這伴隨著 34% 的研發投資增加。較高的特許權使用費收入和來自流行病佐劑銷售的有利組合部分抵消了這些因素。第四季度的銷售額下降了 7%，這反映出由於 Shingrix 的強勁銷售，2020 年的比較艱難。

Turning to Slide 23. Revenues in Consumer Healthcare increased 4%, excluding brands either divested or under review. Including those brands, turnover was flat. Brian outlined the main drivers earlier. The operating margin was 23.3%, up 200 basis points at CER versus last year due to sales growth, including favorable pricing and mix and strong synergy delivery. This was partially offset by a 120 basis point impact from the divested brands in addition to commodity and freight cost pressures. The strong 11% sales growth, excluding brands divestiture under review in Q4, is an encouraging sign of momentum as the business moves into 2022.

轉到幻燈片 23。消費保健品的收入增長了 4%，不包括被剝離或正在審查的品牌。包括這些品牌在內，營業額持平。布賴恩早些時候概述了主要驅動因素。由於銷售增長，包括有利的定價和組合以及強大的協同效應，營業利潤率為 23.3%，按 CER 計算比去年增長 200 個基點。除了商品和運費成本壓力外，剝離品牌的 120 個基點影響部分抵消了這一影響。不包括第四季度正在審查的品牌剝離，強勁的 11% 銷售增長是業務進入 2022 年的一個令人鼓舞的勢頭跡象。

Turning to Slide 24. I'll close with our guidance for new GSK in '22. 2022 also excludes the commercial impact of our COVID solutions. Our guidance is predicated on the Consumer Healthcare business being demerged in mid-2022, and we expect the formal criteria for treating Consumer Healthcare as a discontinued operation to be satisfied with Q2. GSK will continue to consolidate the business for reporting purposes until the planned demerger.

轉到幻燈片 24。我將以我們對 22 年新 GSK 的指導結束。 2022 年還排除了我們 COVID 解決方案的商業影響。我們的指導基於消費者醫療保健業務將在 2022 年年中分拆，我們預計將消費者醫療保健視為已終止業務的正式標準將在第二季度得到滿足。葛蘭素史克將繼續合併業務以用於報告目的，直到計劃分拆為止。

As Brian mentioned earlier, the Consumer Healthcare Capital Markets Day will set out the strategic priorities, key growth drivers and detailed financial information that underpin our confidence in the compelling medium-term outlooks for that company.

正如布賴恩之前提到的，消費者醫療保健資本市場日將列出戰略重點、關鍵增長動力和詳細的財務信息，這些信息將鞏固我們對該公司令人信服的中期前景的信心。

For new GSK, 2022, we'll see a step change in growth. We expect new GSK sales growth to be between 5% and 7% in 2022. Investments in the business for growth will continue in a focused and controlled fashion and so we expect SG&A and R&D to increase the rates similar to sales, whilst we expect cost of goods sold to increase at slower rate than sales.

對於 2022 年的新葛蘭素史克，我們將看到增長的階梯式變化。我們預計 2022 年新的 GSK 銷售額增長將在 5% 至 7% 之間。為實現增長而進行的業務投資將繼續以集中和可控的方式進行，因此我們預計 SG&A 和研發將提高與銷售額相似的速度，同時我們預計成本銷售商品的增長速度低於銷售額。

As a result, our guidance for adjusted operating profit is for between 12% and 14% growth. This includes the anticipated benefit of the related royalties, contributing around 2 percentage points of adjusted operating profit growth.

因此，我們對調整後營業利潤的指導是 12% 至 14% 的增長。這包括相關特許權使用費的預期收益，對調整後的營業利潤增長貢獻了約 2 個百分點。

On outlook for COVID solutions in 2022, based on known binding agreements with governments, we expect that COVID solutions will contribute a similar sales level to 2021 but substantially reduced profit contribution due to increased proportion of lower margin Xevudy sales. We expect this to reduce new GSK adjusted operating profit growth, including COVID solutions in both years, of between 5% to 7%. We'll provide quarterly updates as future contracting and binding agreements progresses.

關於 2022 年 COVID 解決方案的展望，根據與政府的已知約束性協議，我們預計 COVID 解決方案將貢獻與 2021 年相似的銷售水平，但由於利潤率較低的 Xevudy 銷售比例增加，利潤貢獻將大幅降低。我們預計這將使 GSK 調整後的新營業利潤增長（包括這兩年的 COVID 解決方案）降低 5% 至 7%。隨著未來合同和具有約束力的協議的進展，我們將提供季度更新。

With regards to the dividend policy in 2022, the total expected cash distribution and the respective dividend payout ratios for each company are unchanged from what we communicated at our Investor Update last June. GSK expects to pay 49p per share, comprising 44 per share for new GSK and 5p per share representing Consumer Healthcare whilst still part of the group. Consumer Healthcare's dividend in the second half of 2022 is subject to review and approval by the Consumer Healthcare Board. This is expected to be around 3p per share and has been adjusted to reflect the total number of consumer shares that are expected to be an issue upon demerger and more detail is provided in the appendix.

關於 2022 年的股息政策，每家公司的預期現金分配總額和各自的股息支付率與我們在去年 6 月的投資者更新中傳達的信息沒有變化。 GSK 預計每股支付 49 便士，其中包括新 GSK 每股 44 便士和代表消費者保健的每股 5 便士，同時仍是集團的一部分。消費者醫療保健2022年下半年的股息有待消費者醫療保健委員會審查和批准。這預計約為每股 3 便士，並已進行調整以反映分拆後預計將成為問題的消費者股票總數，附錄中提供了更多詳細信息。

Given the complexities associated with demerging a significant operating segment of the company, we'll provide adjusted earnings per share guidance at our Q2 results following the demerger. To help with modeling new GSK, a reconciliation of the 2021 results reflect new reporting format is expected to become available later in the first half. As a reminder, we'll be presenting a single new GSK operating margin in the future.

鑑於與公司重要運營部門分拆相關的複雜性，我們將在分拆後的第二季度業績中提供調整後的每股收益指引。為了幫助對新 GSK 進行建模，2021 年結果的對賬反映了新的報告格式，預計將在上半年晚些時候推出。提醒一下，我們將在未來提供一個新的 GSK 營業利潤率。

In summary, we believe the business momentum built from the excellent work for our teams in 2021 sets us up for a step change in growth from new GSK for 2022.

總而言之，我們相信，我們團隊在 2021 年的出色工作所建立的業務勢頭為我們在 2022 年新葛蘭素史克的增長奠定了基礎。

And with that, I'll hand over to Hal.

有了這個，我將交給哈爾。

Thanks, Ian. I'll provide a short update on our progress in R&D over the past year and highlight some of the key upcoming pipeline milestones.

謝謝，伊恩。我將簡要介紹我們過去一年在研發方面取得的進展，並重點介紹一些即將到來的關鍵管道里程碑。

Please turn to Slide 26. As we set out last June, the transformation of our R&D (inaudible) in 2018 has resulted in a significantly stronger pipeline and improved productivity across multiple metrics. And in 2021, we continue to build on this momentum.

請轉到幻燈片 26。正如我們去年 6 月所述，我們在 2018 年的研發轉型（聽不清）導致管道顯著加強，並提高了多個指標的生產力。到 2021 年，我們將繼續在這一勢頭的基礎上再接再厲。

In terms of late-stage pipeline achievements -- advancements, we achieved the first regulatory approval for 3 new medicines in 2021: Apretude, Xevudy and Jemperli, as well as 7 regulatory submissions. And as Luke mentioned earlier, our approach to life cycle innovation is also delivering with 5 additional approvals in 2021 for Nucala and Benlysta. We also reported positive pivotal data on 3 assets, including daprodustat, which I'll cover in more detail in a moment and started 8 new Phase III trials.

在後期管線成果——進展方面，我們在2021年首次獲得了3個新藥的監管批准：Apretude、Xevudy和Jemperli，以及7個監管提交。正如 Luke 之前提到的，我們的生命週期創新方法也在 2021 年為 Nucala 和 Benlysta 提供了 5 個額外的批准。我們還報告了包括 daprodustat 在內的 3 項資產的積極關鍵數據，我稍後將更詳細地介紹這些數據，並開始了 8 項新的 III 期試驗。

In total, we have delivered 13 major regulatory approvals from 2017, which is top quartile performance for the industry and 4 of these assets have already achieved so-called blockbuster status. As a reminder, we expect the medicines and vaccines approved between 2017 and 2021 to contribute around 60% of new GSK's '21 to '26 sales growth with the anticipated pipeline approvals contributing another 40%. We're also bringing forward the next generation of innovative assets into our pipeline, driven by our focus on the science of the immune system, human genetics and advanced technologies.

從 2017 年開始，我們總共獲得了 13 項主要監管批准，這是行業前四分之一的表現，其中 4 項資產已經達到了所謂的重磅地位。提醒一下，我們預計 2017 年至 2021 年期間批准的藥物和疫苗將貢獻新葛蘭素史克 21 至 26 年銷售增長的 60% 左右，而預期的管道批准將貢獻另外 40%。在我們專注於免疫系統科學、人類遺傳學和先進技術的推動下，我們還將下一代創新資產引入我們的管道。

In 2021, we moved 19 assets into Phase I or Phase II trials, which are the direct result of our focus on human genetics and functional genomics with our overarching vision to use the human as the model organ. An excellent example of this is our anti-IL-18 neutralizing antibody, so-called GSK'806, which is being developed to treat patients with atopic dermatitis where there is strong genetic rationale for this target. The second example is GSK'130, a monoclonal antibody which just entered Phase I and targets IL-7, which is genetically associated with developing multiple sclerosis. In Oncology, our internal work on functional genomics identified more than 10 target candidates in research for evaluation in the field of synthetic lethality.

2021 年，我們將 19 項資產轉移到 I 期或 II 期試驗，這是我們專注於人類遺傳學和功能基因組學以及以人類為模型器官的總體願景的直接結果。一個很好的例子是我們的抗 IL-18 中和抗體，即所謂的 GSK'806，它正在開髮用於治療特應性皮炎患者，該目標具有很強的遺傳原理。第二個例子是 GSK'130，這是一種剛剛進入 I 期並靶向 IL-7 的單克隆抗體，IL-7 在基因上與發展為多發性硬化症有關。在腫瘤學方面，我們在功能基因組學方面的內部工作確定了 10 多個用於評估合成殺傷力領域的研究目標候選者。

Our collaboration with IDEAYA has 3 synthetic lethal targets. The most advanced is our MAT2A inhibitor, which is in Phase I for patients with tumor where NTAP is deleted, which is common in solid tumors. Overall, I'm very excited about the potential of this next wave of medicines and vaccines in our pipeline.

我們與 IDEAYA 的合作有 3 個合成致命目標。最先進的是我們的 MAT2A 抑製劑，該抑製劑處於 I 期，用於治療 NTAP 缺失的腫瘤患者，這在實體瘤中很常見。總的來說，我對我們管道中下一波藥物和疫苗的潛力感到非常興奮。

Please turn to Slide 27. This slide highlights 2 major pipeline achievements delivered towards the end of 2021. I've previously spoken before about the daprodustat, our HIF prolyl hydroxylase inhibitor, the target we chose to pursue because, again, genetic strongly suggested a role in stimulating erythropoiesis. The ASCEND Phase III program recruited over 8,000 patients in well-designed studies using active controls and to deliver very consistent efficacy and safety results in both dialysis and non-dialysis patients. The results uniquely demonstrated that daprodustat met the primary endpoint of noninferiority to (inaudible) stimulating agent in terms of cardiovascular safety and was shown to be as effective as standard of care in treating to a target hemoglobin range. We believe these data positioned daprodustat as a best-in-class oral agent for treating patients with anemia of chronic kidney disease and are on track to submit these data in the first half of this year.

請轉到幻燈片 27。這張幻燈片重點介紹了 2021 年底交付的 2 個主要管道成就。我之前曾談到過 daprodustat，我們的 HIF 脯氨酰羥化酶抑製劑，我們選擇追求的目標，因為遺傳再次強烈建議刺激紅細胞生成的作用。 ASCEND III 期計劃在精心設計的研究中招募了 8,000 多名患者，使用主動控制，並在透析和非透析患者中提供非常一致的療效和安全性結果。結果獨特地表明，達普司他在心血管安全性方面達到了非劣於（聽不清）刺激劑的主要終點，並且在治療目標血紅蛋白範圍時被證明與護理標準一樣有效。我們相信這些數據將 daprodustat 定位為治療慢性腎病貧血患者的同類最佳口服藥物，並有望在今年上半年提交這些數據。

The second key pipeline achievement was the approval of Apretude for the prevention of HIV based on extremely impressive efficacy results. This exciting milestone is well covered by Deborah earlier, so let's turn to Slide 28.

第二個關鍵的管道成就是基於令人印象深刻的療效結果批准 Apretude 用於預防 HIV。這個激動人心的里程碑早前已經被 Deborah 很好地介紹過了，所以讓我們來看一下幻燈片 28。

Looking to the year ahead, this slide focuses on the important pipeline milestones we anticipate in the first half of 2022. RSV disease represents a significant unmet medical need, with RSV infections accounting for around 180,000 hospitalizations each year and about 14,000 deaths in the over 65 population in the United States alone. The unique design of our antigen/adjuvant combination induces a strong neutralizing antibody titers and T cell responses against both RSV A and B in the Phase II trials, which is critical to protect an older adult population for an increased risk for RSV disease.

展望未來一年，這張幻燈片重點介紹了我們預計在 2022 年上半年實現的重要管道里程碑。RSV 疾病代表了一項未得到滿足的重大醫療需求，RSV 感染每年導致約 180,000 人住院，超過 65 人中有約 14,000 人死亡僅美國的人口。我們的抗原/佐劑組合的獨特設計在 II 期試驗中誘導了針對 RSV A 和 B 的強中和抗體滴度和 T 細胞反應，這對於保護老年人群免受 RSV 疾病風險增加至關重要。

From the literature and our trial data, we know that older adults typically have a lower T cell response when compared to younger population. And our RSV older adult vaccine utilizes our AS01 adjuvant to overcome this deficiency. Our RSV older adult trial is expected to read out ahead of our original time lines with headline data expected during the first half of 2022 and filing is anticipated before year-end, potentially putting us on a path for inclusion in the June 2023 SIP meeting.

從文獻和我們的試驗數據中，我們知道與年輕人相比，老年人的 T 細胞反應通常較低。我們的 RSV 老年人疫苗利用我們的 AS01 佐劑來克服這一缺陷。我們的 RSV 老年人試驗預計將在我們最初的時間線之前宣讀，預計將在 2022 年上半年發布標題數據，並預計在年底之前提交，這可能使我們走上 2023 年 6 月 SIP 會議的道路。

Please turn to Slide 29. The next 2 years, we'll see R&D continue to deliver important news flow on several potential new medicines and vaccines within our late-stage pipeline. In 2022, we anticipate late-stage milestones from up to 7 of the 11 (inaudible) and medicines we've highlighted at the investor update in June last year, including those I've already mentioned. I'll take 2 minutes to highlight some of the other readouts that I'm most excited about.

請轉到幻燈片 29。接下來的 2 年，我們將看到研發繼續為我們後期管道中的幾種潛在新藥和疫苗提供重要的新聞流。到 2022 年，我們預計 11 種（聽不清）和我們在去年 6 月投資者更新中強調的藥物中的 7 種將達到後期里程碑，包括我已經提到的那些。我將花 2 分鐘的時間來突出顯示我最感興趣的其他一些讀數。

I'll start with otilimab, where we have 3 Phase III trials reading out in 2022, contrast 1, 2 and 3. These data will define the efficacy and safety of our anti-GM-CSF antibody, which has the potential to deliver an entirely new mechanism of action for patients with rheumatoid arthritis. Data from the Phase IIb trial suggested a unique reduction in pain, which we believe could be driven by CCL17, the most overexpressed protein by monocytes when stimulated by GMCSL. Based on this finding, we moved GSK'279, a CCL17 monoclonal antibody into development to treat patients with RC arthritic pain, and we expect initial data to be available later in the year.

我將從 otilimab 開始，我們將在 2022 年進行 3 項 III 期試驗，對比 1、2 和 3。這些數據將確定我們的抗 GM-CSF 抗體的有效性和安全性，該抗體有可能提供類風濕關節炎患者的全新作用機制。 IIb 期試驗的數據表明疼痛的獨特減輕，我們認為這可能是由 CCL17 驅動的，CCL17 是 GMCSL 刺激時單核細胞過度表達的蛋白質。基於這一發現，我們將 GSK'279（一種 CCL17 單克隆抗體）投入開發，用於治療 RC 關節炎疼痛患者，我們預計將在今年晚些時候提供初步數據。

In addition, we expect data on BLENREP, the pivotal DREAM-3 trial readout in patients with third-line multiple myeloma. This is an important study that will give us the first progression-free survival and overall survival data on BLENREP in a randomized setting. We also anticipate presenting data around the middle of this year on BLENREP in combination with the gamma secretase inhibitor. These data will also help inform our strategy for patients -- for treating patients in the frontline setting.

此外，我們期待 BLENREP 的數據，這是三線多發性骨髓瘤患者的關鍵 DREAM-3 試驗讀數。這是一項重要的研究，它將在隨機環境中為我們提供有關 BLENREP 的第一個無進展生存期和總生存期數據。我們還預計在今年年中左右提供 BLENREP 與 γ 分泌酶抑製劑聯合使用的數據。這些數據還將有助於為我們的患者制定策略——在一線治療患者。

I also want to briefly mention bepirovirsen, our HBV ASO, which we plan to present data on in the middle of the year from our Phase IIb trial investigating the treatment of patients with chronic hep B. There is a significant unmet medical need for these patients with over -- around 300 million patients living with hep B, and the disease is responsible for over 900,000 deaths each year. In addition to these late-stage data readouts, we planned at least 3 major regulatory submissions in '22, including daprodustat, RSV for older adults and BLENREP in the third line setting.

我還想簡要提一下我們的 HBV ASO 貝匹羅韋森，我們計劃在今年年中提供我們的 IIb 期試驗的數據，該試驗調查慢性乙肝患者的治療。這些患者的醫療需求尚未得到滿足超過 - 大約 3 億乙肝患者，該疾病每年導致超過 900,000 人死亡。除了這些後期數據讀出外，我們還計劃在 22 年至少提交 3 項主要監管提交，包括 daprodustat、老年人 RSV 和三線設置中的 BLENREP。

Lastly, we have recently announced several impressive leadership appointments, including Phil Dormitzer as the Head of Vaccines R&D, who joined us from Pfizer; and Hesham Abdullah, who is promoted to the Head of Oncology. In January, we also announced that Tony Wood would be our new Chief Scientific Officer from the 1st of August, and I'm delighted about his appointment. Tony is a person and scientist of the highest quality. He was integral to building our new approach to R&D and his appointment and expertise deepen our commitment to this strategy, and I'm positive that Tony will been an outstanding leader for GSK R&D.

最後，我們最近宣布了幾項令人印象深刻的領導任命，包括從輝瑞加入我們的 Phil Dormitzer 擔任疫苗研發負責人； Hesham Abdullah，晉升為腫瘤學主任。 1 月份，我們還宣布 Tony Wood 將從 8 月 1 日起擔任我們的新首席科學官，我對他的任命感到高興。托尼是最高品質的人和科學家。他是我們建立新的研發方法不可或缺的一部分，他的任命和專業知識加深了我們對這一戰略的承諾，我很肯定托尼將成為葛蘭素史克研發的傑出領導者。

I'm also pleased to remain part of GSK beyond August as I transition to a nonexecutive Board member and support Tony and the team to deliver on the promise of our exciting pipeline.

我也很高興在 8 月之後繼續留在葛蘭素史克，因為我過渡到非執行董事會成員並支持托尼和團隊兌現我們令人興奮的管道的承諾。

So in summary, 2022 will be an exciting year for our high-quality pipeline, and I remain very confident that we'll continue to advance the standard of care for patients and deliver value to shareholders.

因此，總而言之，2022 年對於我們的高質量管道來說將是激動人心的一年，我仍然非常有信心，我們將繼續提高患者護理標準並為股東創造價值。

With that, I'll hand it back to Emma to take over the call.

有了這個，我會把它交給艾瑪來接聽電話。

Thank you. So let's move to Q&A, please. Operator?

謝謝你。所以讓我們進入問答環節，拜託。操作員？

The first question is coming from the line of James Gordon from JPM.

第一個問題來自 JPM 的 James Gordon。

James Gordon, JPMorgan. I just have one question, a question about specialty pharma. So specialty pharma sales were a little bit light versus consensus expectations today. And growth is going to be approximately 10% in '22, which sounds a little bit more cautious than the double-digit medium-term outlook that you issued in June last year. So have things got any tougher for these assets? Is there going to be a bit of a back-end weighted for specialty pharma? And what could drive an inflection, particularly in oncology? Do we need more data? Or is it really about just COVID diagnoses or COVID getting better and then more diagnosis for these conditions?

摩根大通的詹姆斯·戈登。我只有一個問題，一個關於專業製藥的問題。因此，與今天的普遍預期相比，特種藥品的銷售略顯清淡。 22 年的增長將約為 10%，這聽起來比你去年 6 月發布的兩位數中期展望要謹慎一些。那麼這些資產的情況變得更加艱難了嗎？專業製藥公司是否會有一些後端加權？什麼可以推動拐點，尤其是在腫瘤學領域？我們需要更多數據嗎？還是真的只是 COVID 診斷或 COVID 變得更好，然後對這些情況進行更多診斷？

And if I could another question, just a clarification. If I look at the guidance, the 5% to 7% core EBIT headwind for COVID-19 product contribution, it looks like it's effectively assuming that you sell the 1 million doses for Xevudy that you've already got an order for, but there's no more sales at all for the rest of the year. So just a clarification, is that right? The assumption is that beyond builders you've already got, you won't sell any more Xevudy this year.

如果我可以提出另一個問題，請澄清一下。如果我看一下指導意見，即 COVID-19 產品貢獻的 5% 到 7% 的核心 EBIT 逆風，看起來它實際上是假設您銷售了已經訂購的 100 萬劑 Xevudy，但是有在今年剩下的時間裡根本沒有銷售。所以只是澄清一下，對嗎？假設是除了你已經擁有的建築商之外，今年你不會再出售 Xevudy。

Well, I'm going to ask Iain -- thanks, James, for that one question and then clarification, and I'll ask Iain to pick up exactly, first, on the forecast forward for COVID solutions. Just remembering it's not in any of our guidance either for this year or for the year ahead. And obviously, there's still some uncertainty about how that market will play out. We'll come to Iain first.

好吧，我要問伊恩——謝謝詹姆斯，這個問題和澄清，我會問伊恩首先準確地了解 COVID 解決方案的未來預測。只要記住它不在我們今年或未來一年的任何指導中。顯然，該市場將如何發展仍存在一些不確定性。我們先來伊恩。

And then just more broadly on the total outlook, obviously, we've guided more than 5 top line on a 5-year outlook. And as you said, double digit for Specialty, and high single digit for Vaccines. We're very clear that, that isn't at an overall level, something that we're expecting anyone to wait for, which is why we're starting strong and starting now in '22 with 5 to 7. But clearly, the mix of that is dependent on some of the pipeline both coming and recent launches maturing into more scale contributions in Specialty. But I'm going to ask Luke to comment a bit more on some of the shape of that and then perhaps how we can come back to you to talk about some of the pipeline catalysts further out in Specialty Medicines more broadly. But first of all, Iain, on...

然後更廣泛地關注總體前景，顯然，我們在 5 年展望中指導了超過 5 條頂線。正如你所說，專業是兩位數，疫苗是高個位數。我們非常清楚，這不是總體水平，我們希望任何人都在等待，這就是為什麼我們開始強勢並從 22 年開始，從 5 到 7 開始。但顯然，這其中的混合取決於即將推出的一些管道以及最近推出的成熟為專業領域更大規模貢獻的產品。但我要請盧克對其中的一些形式發表更多評論，然後也許我們可以回到你身邊，更廣泛地討論一些在特種藥物中更進一步的管道催化劑。但首先，伊恩，關於...

Yes. Yes. No, easy answer, James, pretty much exactly what we wrote in our earnings release, which we expect Pandemic sales were around GBP 1.4 billion from Xevudy. That reflects binding agreements that we have in place at this point in time. And to the extent there are any further binding agreements that would inform any updates, we'll provide those on a quarterly basis. Okay?

是的。是的。不，簡單的回答，詹姆斯，幾乎完全符合我們在收益發布中所寫的內容，我們預計 Xevudy 的 Pandemic 銷售額約為 14 億英鎊。這反映了我們目前已達成的具有約束力的協議。如果有任何進一步的具有約束力的協議可以通知任何更新，我們將每季度提供一次。好的？

So Luke, in terms of momentum and outlook on Specialty.

所以盧克，就專業的勢頭和前景而言。

Yes. Thanks, James. Look, I think the momentum, for example, on Trelegy, is very strong. We're getting 5 scripts for every one that Breztri gets. Benlysta is very healthy. I think the primary challenges, and we've placed this in the backup in the appendix is just the continued slow recovery of ovarian cancer diagnosis, which is still down by 22%. And debulking surgeries are down by 17%. So that's taking longer to resolve than we were expected, which is obviously very sad. And we expect that when those women present, their disease is going to be more advanced and so that is having an impact. There was also some pricing pressure emerging in the IL-5 class in Q4.

是的。謝謝，詹姆斯。看，我認為勢頭非常強勁，例如在 Trelegy 上。 Breztri 得到的每一個腳本，我們都會得到 5 個腳本。本利斯塔非常健康。我認為主要的挑戰，我們把它放在附錄中的備份只是卵巢癌診斷的持續緩慢恢復，仍然下降了 22%。減瘤手術減少了 17%。所以解決問題的時間比我們預期的要長，這顯然是非常可悲的。我們預計，當這些女性出現時，她們的疾病會更嚴重，因此會產生影響。第四季度 IL-5 級別也出現了一些定價壓力。

And perhaps Deborah, but before we go to Hal, obviously, one of the areas that's going to continue to build in contribution is the innovation in HIV. So Deborah, to you first?

也許還有黛博拉，但在我們去哈爾之前，很明顯，將繼續做出貢獻的領域之一是艾滋病毒的創新。所以黛博拉，首先給你？

Yes. So I think at the Business Investor Update at the end of November, we committed to mid-single-digit CAGR between now and 2026, and that's an acceleration of growth where we've been over the last few years, where if you remember, we've had kind of over the last 3, 1% and then obviously, in 2021, we're at 3%. So you can see that progressive growth acceleration, and we feel very positive about our ability to deliver that mid-single-digit CAGR on the back of the tremendous progress that we've made with Dovato, but also the fact that you'll get more material contribution from Cabenuva certainly 2022 and beyond and Apretude 2023 and beyond. So I'm feeling really excited and confident about the future in the HIV part of Specialty.

是的。所以我認為在 11 月底的商業投資者更新中，我們承諾從現在到 2026 年之間的複合年增長率為中個位數，這是過去幾年我們一直在加速的增長，如果你還記得的話，在過去的 3 年中，我們已經達到了 1%，然後很明顯，到 2021 年，我們達到了 3%。因此，您可以看到漸進式增長加速，我們對我們在 Dovato 取得巨大進步的支持下實現中個位數複合年增長率的能力感到非常樂觀，而且您將獲得Cabenuva 肯定會在 2022 年及以後和 Apretude 2023 年及以後作出更多的物質貢獻。所以我對專業的 HIV 部分的未來感到非常興奮和自信。

Thank you. Hal, and things to add on catalyst to follow.

謝謝你。哈爾，以及接下來要添加的催化劑。

Yes, there's been a lot of catalysts in the last 12 months, as I pointed out, with the 3 regulatory approvals and the 7 major filings, 3 pivotal data readouts in the Phase III starts. I think it's also important now that we have 64 medicines and vaccines in the pipeline, 22 of which are in late-stage pivotal studies, so you're going to be seeing a lot of readouts. Most importantly, in 2022, we've talked about the 11 key assets.

是的，正如我所指出的，在過去的 12 個月裡有很多催化劑，隨著 3 項監管批准和 7 項主要文件，第三階段的 3 項關鍵數據讀數開始了。我認為現在我們有 64 種藥物和疫苗正在研發中也很重要，其中 22 種處於後期關鍵研究中，所以你會看到很多讀數。最重要的是，在 2022 年，我們已經討論了 11 項關鍵資產。

And in 2022, we're hoping that up to 7 of those will actually have readouts, including RSV OA in the first half; otilimab, as I mentioned, in the second half; BLENREP DREAMM-3 in the second half; RSV maternal, which we should get data in the second half; the meninge pentavalent, ABCWY, in the second half; Jemperli will have a readout both in the conversion of the GARNET study as well as data in RUBY. And as I mentioned a little earlier, Phase IIb epirubricin for the [CLEAR] study in HBV. And that, of course, complements the wonderful data that we received earlier with Apretude and the recent approval. So really a lot of -- quite a lot of catalog.

到 2022 年，我們希望其中多達 7 個實際上會有讀數，包括上半年的 RSV OA；正如我所提到的，奧替利單抗在下半場； BLNREP DREAMM-3 下半場； RSV母體，我們應該在下半年得到數據；腦膜五價，ABCWY，在下半場； Jemperli 將在 GARNET 研究的轉換以及 RUBY 中的數據中讀取數據。正如我之前提到的，用於 HBV [CLEAR] 研究的 IIb 期表柔比星。當然，這補充了我們之前收到的 Apretude 和最近批准的精彩數據。所以真的很多——很多目錄。

And I think fundamentally, James, it's just worth reminding ourselves that in New and Specialty, our growth last year was 26% and even excluding the contribution from Xevudy at 14%. So there's a lot of reasons for confidence in strong executional performance of growth and then, of course, all the pipeline to add to that.

我認為從根本上來說，詹姆斯，值得提醒自己的是，在 New and Specialty 領域，我們去年的增長率為 26%，甚至不包括 Xevudy 14% 的貢獻。因此，有很多理由對增長的強勁執行表現充滿信心，當然，還有所有的渠道來增加這一點。

The next question is coming from the line of Keyur Parekh from Goldman Sachs.

下一個問題來自高盛的 Keyur Parekh。

I have 2 questions, please. The first one for Deborah, just following up on your comments about the HIV. And I see that you're guiding to about GBP 2 billion in kind of revenue contribution from the long-acting regimens by 2026. But what I would be interested in, Deborah, is your perspective on how do you see that long-acting market developing beyond 2026 into the kind of the 2030s given the news flow we've had from islatravir and kind of just the early feedback you've had on the prep launch? So just kind of how are you framing that longer-term outlook for that business?

我有2個問題，請。黛博拉的第一個，只是跟進你對艾滋病毒的評論。而且我看到你正在指導到 2026 年長效方案帶來約 20 億英鎊的實物收入貢獻。但我感興趣的是，黛博拉，你對長效市場的看法鑑於我們從 islatravir 獲得的新聞流以及您對準備發布的早期反饋，從 2026 年發展到 2030 年代的那種？那麼，您如何為該業務制定長期前景？

And then secondly, Hal, many congratulations on all your successes and kind of best of luck in your new role. But as you sit here today and look at the progress kind of Glaxo have made from an R&D perspective over the last few years, how much of what you set out to do at the start have you achieved so far? How much more kind of you think you -- the kind of Glaxo the company needs to achieve? And what role do you think you might be playing in that from a nonexecutive perspective?

其次，Hal，非常祝賀你取得的所有成功，並祝你在新角色中好運。但是，當您今天坐在這裡，看看葛蘭素史克在過去幾年中從研發的角度所取得的進展時，您一開始就打算做的事情，到目前為止，您實現了多少？你認為你還有多少——公司需要實現的那種葛蘭素史克？從非執行的角度來看，您認為您可能會在其中扮演什麼角色？

Okay. We'll go directly to Deborah and then Hal, please.

好的。我們將直接去找黛博拉，然後是哈爾，請。

Yes. So thanks for the questions. So I mean we see the long-acting market from a treatment perspective to be about GBP 4 million to GBP 5 million in value by the end of the 2030s. And actually, by the end of the 2020s, we see a GBP 4 billion to GBP 5 billion in value for the market. So both the same kind of value from a long-acting study for the 2020 (inaudible). I think despite the fact that we've seen islatravir have some challenges, we've seen that Gilead are also extremely committed to long-acting themselves with lenacapavir, and they outlined in their results, obviously, all the partners that they're looking at for lenacapavir.

是的。所以謝謝你的問題。所以我的意思是，從治療的角度來看，到 2030 年代末，我們認為長效市場的價值約為 400 萬至 500 萬英鎊。實際上，到 2020 年代末，我們看到的市場價值將達到 40 億至 50 億英鎊。因此，從 2020 年的長效研究（聽不清）來看，兩者的價值相同。我認為儘管我們已經看到 islatravir 面臨一些挑戰，但我們已經看到吉利德也非常致力於使用 lenacapavir 進行長效治療，他們在結果中概述了他們正在尋找的所有合作夥伴在為lenacapavir。

So I think what you're hearing from both of the big players in the market is that there is a big opportunity to serve the needs of patients by delivering innovative new medicines into both the prevention and the treatment part of the market. The other thing that I find encouraging, so obviously, Merck will continue to look at islatravir, but the piece that I think is really encouraging is the real energy around the evolution of the prep market in the United States.

因此，我認為您從市場上的兩大參與者那裡聽到的是，通過向市場的預防和治療部分提供創新的新藥來滿足患者的需求是一個巨大的機會。另一件讓我感到鼓舞的是，很明顯，默克公司將繼續關注 islatravir，但我認為真正令人鼓舞的是圍繞美國製劑市場發展的真正能量。

So if you remember, ending the epidemic is a commitment that there will be significantly less new infections as the decade progresses, the point at which there is a 90% reduction by 2030 and the government in the U.S. is extremely energized at the moment around how they're going to deliver against that target. There's a lot of dialogue occurring, and there's a lot of encouraging sounds about how we could see that prep market evolve, given that only 23% of those that could benefit from prep are actually getting a medicine today.

因此，如果您還記得，結束流行病是一項承諾，即隨著十年的進展，新感染病例將顯著減少，到 2030 年將減少 90%，而美國政府目前非常精力充沛。他們將實現這一目標。有很多對話正在發生，並且有很多令人鼓舞的聲音關於我們如何看到準備市場的發展，因為今天只有 23% 可以從準備中受益的人實際上得到了藥物。

So I think the numbers that we talked about at BIU in June and again in November are still what we were expecting in terms of long-acting treatment markets, long-acting prep market, both each being around GBP 4 billion to GBP 5 billion by the end of the [2022].

所以我認為我們在 6 月和 11 月在 BIU 討論的數字仍然是我們對長效治療市場和長效準備市場的預期，兩者都在 40 億英鎊到 50 億英鎊左右。 [2022] 年末。

The other thing is, I mean, and maybe worth mentioning is the very exciting next-gen pipeline that's coming through in longer acting that you and Kim covered off in November, where when we get into longer-acting, longer-acting is beyond the near term where we're launching.

另一件事是，我的意思是，也許值得一提的是非常令人興奮的下一代管道，它正在通過你和金在 11 月報導的長效，當我們進入長效時，長效超越了近期我們將在哪裡推出。

Yes, we're really excited about that. So we have, if you remember, 3 areas where we're really focusing: an at-home treatment; an ultra long-acting treatment, which will be clinic delivered; and then obviously, we're focusing on cure. And so where we are today with Apretude and Cabenuva, we're absolutely not stopping there. That's why we're so confident about our ability to move past the dolutegravir loss exclusivity and still replace a lot of that revenue that is lost and have a very vibrant HIV business at the end of the decade and beyond.

是的，我們對此感到非常興奮。因此，如果您還記得的話，我們有 3 個我們真正關注的領域：在家治療；一種超長效治療，將在診所進行；然後很明顯，我們專注於治愈。所以我們今天與 Apretude 和 Cabenuva 合作的地方，我們絕對不會止步於此。這就是為什麼我們對我們超越 dolutegravir 損失排他性的能力如此有信心，並且仍然可以彌補損失的大量收入，並在本世紀末及以後擁有非常活躍的 HIV 業務。

So obviously, we've got integrated at the core, both with cabotegravir and then the next generations that we've agreed to in-license from Shionogi. And then we've got the partner options that we're looking at, and we should be able to pick a partner for cabotegravir for at-home and long-acting in 2024 as data reads out and informs our choices. So really excited about the pathway, which is very clear before us and the choice points and when data will be available are also very clear, and we'll keep you all updated.

很明顯，我們已經在核心集成了 cabotegravir，然後是我們同意從 Shionogi 獲得許可的下一代。然後我們得到了我們正在研究的合作夥伴選項，隨著數據讀出並告知我們的選擇，我們應該能夠在 2024 年為 cabotegravir 選擇一個在家中和長效的合作夥伴。這條路徑非常令人興奮，這在我們面前非常清楚，選擇點和何時可用數據也非常清楚，我們會及時通知大家。

Thank you. Hal?

謝謝你。哈爾？

Thanks for the comment question, Keyur. First, let me say I'm actually very proud of what we in the R&D organization have accomplished over the past 4 years. There's so many different metrics one could use to highlight that. Today, the pipeline has 64 medicines and vaccines, 22 of which are in pivotal studies. We have 13 novel assets in Phase III. As Emma mentioned earlier, we've doubled the number of Phase III assets over the last couple of years. Probably the most important metric that I look at is how much of the R&D success and the pipeline are driving the CAGRs that we are proposing, which are top quartile relative to our peers.

感謝您的評論問題，Keyur。首先，讓我說，我對我們研發部門在過去 4 年所取得的成就感到非常自豪。有很多不同的指標可以用來強調這一點。如今，該管道有 64 種藥物和疫苗，其中 22 種處於關鍵研究階段。我們在第三階段擁有 13 項新資產。正如 Emma 之前提到的，在過去幾年中，我們將第三階段資產的數量翻了一番。可能我看到的最重要的指標是研發成功和管道在多大程度上推動了我們提議的複合年增長率，相對於我們的同行而言，複合年增長率最高。

And when you look back, there's been 13 new medicines and vaccines approved over the last 4.25 years or so, and that's driving about 60% of really terrific performance that we've committed to. And importantly, on a risk-adjusted basis, the late-stage pipeline. And this again excludes all of Phase I and Phase II is expected on an adjusted basis to drive another 40% of that growth. So I think those are really important metrics. There's quite a lot of other metrics. But I think we've made quite a bit of progress.

回顧過去，在過去 4.25 年左右的時間裡，有 13 種新藥和疫苗獲批，這推動了我們承諾的 60% 的真正出色表現。重要的是，在風險調整的基礎上，後期管道。這再次排除了所有第一階段和第二階段預計在調整後將推動另外 40% 的增長。所以我認為這些都是非常重要的指標。還有很多其他指標。但我認為我們已經取得了相當大的進步。

You asked what's not finished. Well, I think if you think about being the head of R&D at any pharma company or biotech company, you never leave the job finished. The job -- there's always more assets that you can progress. There's more programs. There's more life cycle innovation. As long as the success rate is where it is, there's still an enormous opportunity to transform how targets are discovered. And I'm very excited about how much progress we've made on using the human as the model organism, using human genetics, functional genomics and machine learning to evolve our strategy.

你問什麼還沒有完成。好吧，我認為如果你想成為任何製藥公司或生物技術公司的研發主管，你永遠不會離開工作完成。這份工作——總是有更多的資產可以讓你進步。還有更多的節目。還有更多的生命週期創新。只要成功率在哪裡，仍然有巨大的機會來改變目標的發現方式。我對我們在使用人類作為模式生物、使用人類遺傳學、功能基因組學和機器學習來發展我們的戰略方面取得的進展感到非常興奮。

In fact, if you think about what's coming, we have around 40 collaboration projects with 23 and me on genetically validated targets. We have 10 synthetic lethal programs that were internally developed. We have 3 with IDEAYA. We have programs with the Broad. We have programs with (inaudible), a number of collaboration programs, the anti-sortilin program. So a number of genetically validated targets that over the next 5 to 10 years are going to evolve. I'm looking forward to my transition from being the CSO to the Board member to help Tony Wood, who is an outstanding leader, an outstanding scientist and outstanding person. And I'm hoping that I can play some role in helping him evolve our strategy to be able to accomplish all these things that we're hoping to do.

事實上，如果你想想接下來會發生什麼，我們有大約 40 個合作項目，我和 23 個合作項目是基因驗證的目標。我們有 10 個內部開發的合成致死程序。 IDEAYA 有 3 個。我們有廣泛的計劃。我們有一些項目（聽不清）、一些合作項目、反分選項目。因此，在未來 5 到 10 年內，許多經過基因驗證的目標將不斷發展。我期待著從 CSO 過渡到董事會成員，以幫助 Tony Wood，他是一位傑出的領導者、傑出的科學家和傑出的人。我希望我能在幫助他發展我們的戰略方面發揮一些作用，以便能夠完成我們希望做的所有這些事情。

And I would just reiterate that what matters most in these transitions is extremely well-planned and strategic and thoughtful succession. We are all very confident we're going to accelerate the momentum of the execution of this strategy that objectively and quantitatively can really be seen to be bearing results already. And we're absolutely thrilled that how it's still going to be part of that adventure as a Board member, as a Science Committee member and with some additional commitments that I know he's more than happily made to support the R&D organization, its advisory boards some connectivity in his part of the world. And we are obviously very proud of him for his next steps, too, and excited for the path ahead.

我只想重申，在這些過渡中最重要的是經過精心策劃、戰略性和深思熟慮的繼任。我們都非常有信心，我們將加快執行這一戰略的勢頭，從客觀和數量上可以看出，該戰略已經真正取得成果。作為董事會成員、科學委員會成員以及一些額外的承諾，我知道他非常樂意支持研發組織及其顧問委員會的一些其他承諾，我們對此感到非常興奮。他所在地區的連通性。我們顯然也為他的下一步工作感到非常自豪，並對未來的道路感到興奮。

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

下一個問題來自美國銀行的 Graham Parry。

So firstly, on the RSV vaccine, it looks like Pfizer is on track to publish RSV older adult vaccine data Q1 or Q2, possibly ahead of GSK. Are you seeing that the hurdle rates for both their vaccine and yours is the same level of protection you saw in J&J's CYPRESS Phase II trial? And how confident are you that your vaccine can match those levels? And do you see that by not waiting for a full RSV season that Pfizer could gain any sort of time advantage to the market to you? Or is it just a seasonal issue?

因此，首先，在 RSV 疫苗方面，輝瑞似乎有望在第一季度或第二季度發布 RSV 老年人疫苗數據，可能在葛蘭素史克之前。您是否看到他們的疫苗和您的疫苗的障礙率與您在強生的 CYPRESS II 期試驗中看到的保護水平相同？你對你的疫苗能達到這些水平有多大信心？您是否認為輝瑞可以通過不等待完整的 RSV 季節為您獲得市場上的任何時間優勢？還是只是季節性問題？

And then secondly, on COGS, that was negatively impacted by both Xevudy and write-downs in the quarter. Just wonder if you could quantify how much for each basis points than just the right sort of longer-term COGS ratio ex pandemic we should be thinking about?

其次，在 COGS 上，這受到了 Xevudy 和本季度減記的負面影響。只是想知道您是否可以量化每個基點的多少，而不是我們應該考慮的正確類型的長期銷貨成本比？

Right. So briefly, Iain, could you comment on COGS and then Hal on RSV?

對。簡而言之，Iain，您能先評論一下 COGS，然後再評論一下 Hal 的 RSV 嗎？

Well, Graham, again, we provide a little bit of a steer in terms of the impact of Xevudy, in terms of operating margin. We participate in about 27.3% of the economics from sales in Xevudy, so when you sort of translate that through to the overall profitability. We provide some steer in our earnings release in terms of what that means. There is, within the team, a very strong focus on continuing to drive productivity and efficiency across the supply chain through COGS. And as we talked about in the investor update in June, that focus remains consistent and is part of what informs our progress in operating profit growth in 2022 and beyond.

好吧，格雷厄姆，我們再次就 Xevudy 的影響和營業利潤率提供一點指導。我們參與了 Xevudy 約 27.3% 的銷售經濟，所以當你將其轉化為整體盈利能力時。就這意味著什麼，我們在收益發布中提供了一些指導。團隊內部非常重視通過 COGS 繼續提高整個供應鏈的生產力和效率。正如我們在 6 月的投資者更新中談到的那樣，這一關注點保持一致，並且是我們在 2022 年及以後的營業利潤增長方面取得進展的一部分。

Hal?

哈爾？

Yes. Thanks, Graham. Our RSV program is actually ahead of schedule, as I mentioned, enrollment is completed, and we expect the data for the trial to read out this half, H1 '22. In terms of -- it's important to keep in mind that we have a pretty unique vaccine because we, as you know, have the protein with the AS01 adjuvant. And we think this is a very important component because, as I mentioned earlier, the elderly who are obviously at risk for the complications of this infection over time lose their both adaptive and innate sense of being able to combat this infection.

是的。謝謝，格雷厄姆。正如我所提到的，我們的 RSV 計劃實際上提前了，註冊已完成，我們預計試驗數據將在 22 年上半年公佈。就 - 重要的是要記住，我們有一種非常獨特的疫苗，因為如你所知，我們擁有帶有 AS01 佐劑的蛋白質。我們認為這是一個非常重要的組成部分，因為正如我之前提到的，隨著時間的推移，顯然處於感染並發症風險中的老年人失去了能夠對抗這種感染的適應性和先天意識。

And particularly, you see an abnormality in their T cell response. So we're optimistic that the combination of the right protein in the RSV-A, which neutralizes both the RSV-A and B isoforms of the virus as well as having the T cell modulatory component with the adjuvant, will give us the highest chance of success in this -- for this vaccine.

特別是，您會看到他們的 T 細胞反應異常。因此，我們樂觀地認為，RSV-A 中正確的蛋白質組合（中和病毒的 RSV-A 和 B 同種型以及具有 T 細胞調節成分和佐劑）將為我們提供最大的機會在這方面取得了成功 - 對於這種疫苗。

The next question is coming from the line of Simon Baker, Redburn.

下一個問題來自 Redburn 的 Simon Baker。

Just going back to Graham's question on COGS. Iain, you pointed out the impact of Xevudy, but also in the press release, you discussed other headwinds on the gross margin in 2021. Presumably in light of the comments you made on R&D, SG&A and the guidance for operating profit, they will fall away in their entirety in 2022. But I just wonder if you could give us any other non-Xevudy tailwinds and headwinds we should be thinking about for COGS in '22?

回到格雷厄姆關於 COGS 的問題。 Iain，您指出了 Xevudy 的影響，但在新聞稿中，您還討論了 2021 年毛利率的其他不利因素。根據您對研發、SG&A 和營業利潤指導的評論，它們可能會下降到 2022 年將完全消失。但我只是想知道你是否能給我們提供任何其他非 Xevudy 順風和逆風，我們應該在 22 年考慮 COGS？

What I was referring to in '21 was specifically some higher inventory costs within COGS and lower demand, particularly within the Vaccines business. That was one key driver. Another factor, which was possibly more noticeable within our Consumer business, but as well as it was managed there, equally managed within the biopharma business was around input costs. So freight, as an example, where I think the team was incredibly successful in driving productivity to offset some of that inflationary pressures, that focus and we believe capability continues through 2022.

我在 21 年所指的具體是 COGS 中較高的庫存成本和較低的需求，特別是在疫苗業務中。那是一個關鍵驅動因素。另一個可能在我們的消費者業務中更為明顯的因素，除了在那裡進行管理外，在生物製藥業務中同樣受到管理的是投入成本。因此，以貨運為例，我認為該團隊在提高生產力以抵消部分通脹壓力方面取得了令人難以置信的成功，這一重點和我們相信能力將持續到 2022 年。

So there are a couple of factors that were unique to '21 that I've mentioned that we do not see at this point in time recurring in 2022. And then just our overall focus on driving efficiency productivity through the commercial cycle across our businesses in managing cost of goods sold overall where we felt a good track record over the course of the next -- over the last couple of years, we expect to be able to sustain over the coming years. So it's just -- it's good old-fashioned productivity through the supply chain, the procurement channels, good linkage with commercial cycle in terms of understanding demand in market and managing inventory accordingly.

因此，我提到了 21 年獨有的幾個因素，我們目前看不到 2022 年會再次出現。然後，我們整體專注於在整個商業周期中提高效率生產力管理整體銷售成本，我們認為在接下來的過程中記錄良好 - 在過去幾年中，我們預計能夠在未來幾年維持。所以它只是——通過供應鏈、採購渠道、在了解市場需求和相應地管理庫存方面與商業周期的良好聯繫，這是一種很好的老式生產力。

(Operator Instructions) And the next one is coming from Tim Anderson, Wolfe Research.

（操作員說明）下一個來自 Wolfe Research 的 Tim Anderson。

I have a question, just a pipeline question. Otilimab, you called out the Phase III readout in RA in the second half as an important 2022 catalyst. To me, that Phase II data always looked a little questionable. And I know Glaxo is the only company chasing this mechanism. Sometimes that's a red flag because most of the time, other companies crowd into new and exciting areas. So my question is your confidence in that readout and in this being a commercially meaningful asset, I'm trying to figure out how much this sort of thing is in your kind of longer-term forecast and how much risk adjusting you do on this particular asset?

我有一個問題，只是一個管道問題。 Otilimab，您在下半年將 RA 的 III 期讀數稱為 2022 年的重要催化劑。對我來說，第二階段的數據總是看起來有點可疑。而且我知道葛蘭素史克是唯一一家追求這種機制的公司。有時這是一個危險信號，因為大多數時候，其他公司都擠進了新的和令人興奮的領域。所以我的問題是你對那個讀數的信心，並且這是一個具有商業意義的資產，我試圖弄清楚這種事情在你的長期預測中有多少，以及你對這個特定的風險進行了多少調整資產？

Hal?

哈爾？

Yes. Tim, thanks for the question. So Tim, it's a pretty interesting pathway. It's very novel. So typically, when you have such a novel pathway, you don't see the so-called crowding until, of course, the data reads out positively, which then results in crowding. I'm pretty optimistic this trial will hit, to be honest. You have to remember that there's a design where it's against placebo for the first 12 weeks and then active comparator against IL-6 in one study and the JAK class and the other.

是的。蒂姆，謝謝你的問題。所以蒂姆，這是一條非常有趣的途徑。很新奇。所以通常情況下，當你有這樣一個新穎的途徑時，你不會看到所謂的擁擠，當然，直到數據讀取為正，然後導致擁擠。老實說，我非常樂觀地認為這次試驗會成功。您必須記住，有一種設計是在前 12 週針對安慰劑，然後在一項研究和 JAK 類和另一項研究中針對 IL-6 進行主動比較。

The signal for efficacy, I think, was pretty clear. But your point is well taken that not every endpoint in the Phase IIb was positive, but quite a few work. I think the area that is a little more speculative, but again, I'm cautiously optimistic is where we saw signals to a more significant reduction in the clinical pain scores than one would expect for the reduction in things like Fed rate and CRP levels that are biochemistry measures of the disease severity. We read that data carefully and overlaid it with the preclinical data where we had mouse data with the CCL17 knockout, which as I mentioned earlier, the most overexpressed protein when GM-CSF is applied to monocytes.

我認為，功效的信號非常明確。但你的觀點是正確的，並非 IIb 階段的每個終點都是積極的，但有不少工作。我認為這個領域更具投機性，但我再次謹慎樂觀的是，我們看到臨床疼痛評分降低的信號比美聯儲利率和 CRP 水平降低的預期更顯著。是疾病嚴重程度的生化指標。我們仔細閱讀了這些數據，並將其與臨床前數據重疊，其中我們有 CCL17 敲除的小鼠數據，正如我之前提到的，當 GM-CSF 應用於單核細胞時，這是最過度表達的蛋白質。

And in that CCL17 knockout mouse study within an osteoarthritic neuropathic pain model, there was a dramatic reduction in pain with the knockout. And so that gave us more credibility that, that signal, if you will, in Phase IIb might be real. And again, we're going to have readout from the CCL17 MAB data this -- actually probably in Q2, maybe Q3. And I think that will give us further confidence in the program.

在骨關節炎神經性疼痛模型中的 CCL17 敲除小鼠研究中，敲除後的疼痛顯著減輕。所以這給了我們更多的可信度，如果你願意的話，這個信號在 IIb 階段可能是真實的。再一次，我們將從 CCL17 MAB 數據中讀出這個——實際上可能在第二季度，也許是第三季度。我認為這將使我們對這個項目更有信心。

But again, just to highlight, I'm reasonably optimistic that this will actually benefit patients. It will be a novel class. And hopefully, we'll see some important reductions in pain. Maybe I can just turn it over to Luke to comment on his interest in the commercial component and how he sees this sitting in the landscape of RA patients.

但再次強調，我相當樂觀地認為這實際上會使患者受益。這將是一堂新穎的課。希望我們能看到一些重要的疼痛減輕。也許我可以把它交給盧克來評論他對商業部分的興趣，以及他如何看待這坐在 RA 患者的風景中。

Sure. Thanks, Hal. Thanks, Jim, for the question. I mean the numbers of patients here are enormous, right? I mean there's about 1 million in the U.S. on biologics from JAKs. Many of them are cycling as we know. What's interesting if you look at the new data with JAKs, we have market readouts that indicates about 65% of doctors want to reduce their usage of JAKs and that there could be an opportunity for alternative non-JAK, non-TNF mechanism for about 40%. So there's clearly a demand for patients.

當然。謝謝，哈爾。謝謝吉姆的問題。我的意思是這裡的病人數量是巨大的，對吧？我的意思是在美國有大約 100 萬來自 JAK 的生物製品。正如我們所知，他們中的許多人都在騎自行車。有趣的是，如果您查看 JAK 的新數據，我們的市場讀數表明大約 65% 的醫生希望減少 JAK 的使用，並且可能有機會使用替代非 JAK、非 TNF 機制約 40 %。因此，顯然對患者有需求。

I think the generic association and biosimilars are also going to move patients on to targeted therapies earlier and, therefore, will cycle earlier. I think for the other programs, there's been GM-CSF in the past and a number of them have had some issues in preclinical nonhuman primate models, et cetera. So again, hopefully, we can thread the needle here as Hal said, contrast 3, I think, is really interesting against the IL-6, which is naturally a primary competitor. And then, of course, we've got contracts 1 or 2 against (inaudible) and methotrexate by itself. So I think an interesting program.

我認為仿製藥協會和生物仿製藥也將使患者更早地接受靶向治療，因此會更早地循環。我認為對於其他項目，過去有 GM-CSF，其中一些在臨床前非人類靈長類動物模型等方面存在一些問題。再次，希望我們可以像 Hal 所說的那樣在這裡穿針引線，我認為對比 3 對 IL-6 非常有趣，IL-6 自然是主要競爭對手。然後，當然，我們有針對（聽不清）和甲氨蝶呤本身的合同 1 或 2。所以我覺得一個有趣的節目。

Next question is coming from the line of Emmanuel Papadakis from DB.

下一個問題來自 DB 的 Emmanuel Papadakis。

Maybe I take a question on vaccines, please. Flu market outlook has been pretty topical of late. We've heard market leaders talk at length about reasons to believe in the Brazilian outlook for based (inaudible) vaccine. In fact, I would love to hear your perspective on the room for mRNA-based vaccines to improve upon both the production aspects and risk benefit current-based vaccines over the coming years, given you have some involvement in both sides to that equation. Perhaps you could also take the opportunity to give us a quick update on 2 of our partnership on both the second-gen COVID and lead programs.

請教一個關於疫苗的問題。流感市場前景最近很熱門。我們已經聽到市場領導者詳細討論了相信巴西基礎（聽不清）疫苗前景的理由。事實上，我很想听聽你對基於 mRNA 的疫苗在未來幾年改進生產方面和風險收益基於當前疫苗的空間的看法，因為你在這個等式的雙方都有一些參與。也許您也可以藉此機會向我們簡要介紹一下我們在第二代 COVID 和先導計劃方面的兩個合作夥伴關係。

Sure. Well, why don't we hear from Roger, just on the more strategic outlook for flu. I know we also covered that at the capital markets update briefly and then, Hal, come back to you in terms of the mRNA approach.

當然。好吧，我們為什麼不聽羅傑的意見，只是關於流感的更具戰略意義的前景。我知道我們在資本市場更新中也簡要介紹了這一點，然後，哈爾，就 mRNA 方法回到你身邊。

Thanks very much for the question. I think as we covered last year, the update, what we see is flu is a real opportunity area, to be honest. There's significant disease burden, as you well know. But also when you look at a plot of vaccine efficacy -- it's the one area that stands out that's crying out for innovation to move an on average efficacy level of 50%, some way higher. I think mRNA is a very exciting technology. It's one that we are investing in significantly. It's one that we think could potentially differentiate us as well.

非常感謝這個問題。老實說，我認為正如我們去年報導的那樣，更新，我們看到的是流感是一個真正的機會領域。眾所周知，疾病負擔很重。但是，當您查看疫苗功效圖時-這是一個突出的領域，它迫切需要創新以將平均功效水平提高 50%，甚至更高。我認為 mRNA 是一項非常令人興奮的技術。這是我們正在大力投資的一個。我們認為這也可能使我們與眾不同。

I think the opportunity is that differentiation and our CureVac partnership with Hal, which I will go into, we're looking at both blue and also looking at a universal flu option as well. I wouldn't forget Ag, is something that's going to be a long as a technology for a number of years, and we'll continue to maximize that. But we're allocating significant capital into the mRNA play to ensure that we look to differentiate.

我認為機會在於這種差異化以及我們與 Hal 的 CureVac 合作夥伴關係，我將討論這一點，我們正在研究藍色和通用流感選項。我不會忘記 Ag，它作為一項技術將持續多年，我們將繼續將其最大化。但我們正在為 mRNA 遊戲分配大量資金，以確保我們尋求差異化。

Obviously, the challenge with mRNA in a multi-deal in vaccine, which flu is, is trying to solve this reactogenicity ceiling actually that you can hit with mRNA and I think it's going to take a little bit of time to optimize any mRNA platform to be able to deliver that as well. But our strategy is clear: continue to maximize flu in the (inaudible), develop our PS and mRNA platform that can get a flu solution to deliver a higher-performing flu efficacy.

顯然，在流感疫苗的多重交易中，mRNA 面臨的挑戰是試圖解決這個反應原性上限，實際上你可以用 mRNA 來解決這個問題，我認為優化任何 mRNA 平台都需要一些時間。也能夠做到這一點。但我們的策略很明確：繼續在（聽不清）中最大限度地增加流感，開發我們的 PS 和 mRNA 平台，以獲得流感解決方案，以提供更高性能的流感療效。

Yes. Thanks, Roger. Thanks, Emmanuel, for the question. I think it's pretty clear to the world now that mRNA is a disruptive technology that's really going to transform, to some extent, how we think about vaccines, both because of its advantage in terms of speed from sequence of a virus or the knowledge of what virus is going to be endemic at that phase like in flu. But the longer you have to figure that out, the more likely you are to get the right valence in your vaccine. And so that will be a unique opportunity.

是的。謝謝，羅傑。謝謝，伊曼紐爾的問題。我認為現在全世界都非常清楚 mRNA 是一種顛覆性技術，它確實會在一定程度上改變我們對疫苗的看法，無論是因為它在病毒序列速度方面的優勢，還是因為它在了解什麼方面的優勢。病毒將像流感一樣在那個階段流行。但是，您必須弄清楚這一點的時間越長，您就越有可能在疫苗中獲得正確的化合價。所以這將是一個獨特的機會。

And as alluded to by Roger, the other thing is that if you can have a polyvalent vaccine, the efficacy is likely to go up relative to a monovalent vaccine. So mRNA is -- has a significant potential in flu, and we should be in the clinic with a multivalent mRNA vaccine in 2022, and we're proud of that with CureVac. I think the key thing with multivalent vaccines and mRNA is, of course, the more transcript you put into a patient, the risk is higher reactogenicity. Some of that's somewhat solved by modifying the basis. But even with that, as we saw from some of the Moderna data, we're going to have to continue to work on that.

正如羅傑所暗示的那樣，另一件事是，如果您可以接種多價疫苗，則相對於單價疫苗，功效可能會提高。所以 mRNA 在流感中具有巨大的潛力，我們應該在 2022 年在臨床上使用多價 mRNA 疫苗，我們為 CureVac 感到自豪。我認為多價疫苗和 mRNA 的關鍵當然是，你給病人輸入的轉錄本越多，風險就越高。通過修改基礎可以解決其中的一些問題。但即便如此，正如我們從 Moderna 的一些數據中看到的那樣，我們將不得不繼續努力。

And one of the strategies that we're pursuing that we're excited about is whether we can lower the dose of the transcript by optimizing its stability and how effectively it's translated, more protein for a given amount of mRNA. And we think that the proprietary technology developed by CureVac with this optimization of the flanking the transcript, the 5 prime and 3 prime regions that were done through some pretty sophisticated machine learning, we think this will allow us to lower the dose or if you could think of it as keeping the same dose, but with a larger number of valents and have both immunogenic and well-tolerated, limited reactogenicity to be able to develop a best-in-class for vaccine.

我們正在追求的讓我們興奮的策略之一是，我們是否可以通過優化其穩定性以及它的翻譯效率來降低轉錄物的劑量，為給定量的 mRNA 提供更多的蛋白質。我們認為，CureVac 開發的專有技術通過對側翼轉錄本的優化，通過一些非常複雜的機器學習完成了 5 個素數和 3 個素數區域，我們認為這將使我們能夠降低劑量，或者如果你可以的話將其視為保持相同的劑量，但具有更多的價，並且具有免疫原性和耐受性，反應原性有限，能夠開發出同類最佳的疫苗。

Thanks, Hal.

謝謝，哈爾。

I should also mention just to complete this, we'll have 2 other mRNA vaccines in the clinic this year as well for COVID. So at least 3 mRNA vaccines in '22.

我還應該提到，為了完成這項工作，今年我們將在臨床上還有另外兩種 mRNA 疫苗用於 COVID。所以在 22 年至少有 3 種 mRNA 疫苗。

Yes. And great under new Vaccine's leadership.

是的。在新疫苗的領導下很棒。

Yes, yes.

是的是的。

We're confident.

我們有信心。

Next one is coming from Jo Walton from Credit Suisse.

下一位來自瑞士信貸的 Jo Walton。

I'm afraid I'm going to go back to the margin question. On Page 24, you tell us that you're going to have 5% to 7% top line growth, 12% to 14% adjusted growth, all excluding COVID, and we know that, that includes 2 points from Gilead. On Page 36, you tell us that SG&A and R&D are going to go up in line with sales, and it's the COGS that's going to go up less than sales. So there's a very big COGS improvement that we should expect in 2022.

恐怕我要回到邊際問題了。在第 24 頁，您告訴我們，您將獲得 5% 至 7% 的收入增長，12% 至 14% 的調整後增長，所有這些都不包括 COVID，我們知道，這包括來自吉利德的 2 分。在第 36 頁，您告訴我們 SG&A 和 R&D 將與銷售額同步增長，而 COGS 的增長將低於銷售額。因此，我們應該預計到 2022 年，COGS 會有非常大的改進。

So my question is, if we were -- and we obviously don't have this data to look at just the COGS of new GSK, how far adrift of your peer group do you think you are so that we can get some guide as to whether the majority of the margin gains that we're expecting, not just in 2022, but in '23, '24, et cetera, are going to come from COGS? And how much are going to be able to come from a winding down of SG&A? I'm assuming that R&D will continue to grow strongly.

所以我的問題是，如果我們是——而且我們顯然沒有這些數據來查看新葛蘭素史克的銷貨成本，你認為你與同行群體相差多遠，以便我們可以獲得一些指導我們預期的大部分利潤增長，不僅在 2022 年，而且在 23 年、24 年等，是否將來自 COGS？ SG&A 的倒閉能帶來多少收益？我假設研發將繼續強勁增長。

Yes. So we said and we say again, Jo, is that we'd expect to grow SG&A and this is very much customer-facing SG&A. So it's focused on supporting top line growth and engagement with patients and customers. So the, if you like, the component that is oriented around functional support still has a trajectory that is flat to down. SG&A, we'd expect to be similar levels, but slightly below revenue growth. And the same is true from an R&D perspective, although it will continue to grow. It's going to be similar too but possibly slightly below revenue growth.

是的。所以我們說，我們再說一遍，Jo，我們希望增長 SG&A，這是非常面向客戶的 SG&A。因此，它專注於支持收入增長以及與患者和客戶的互動。因此，如果您願意，以功能支撐為導向的組件仍然具有從平到下的軌跡。 SG&A，我們預計會達到類似水平，但略低於收入增長。從研發的角度來看也是如此，儘管它會繼續增長。它也將相似，但可能略低於收入增長。

In terms of productivity coming through cost of goods sold, part of this is driven by top line. So we're seeing a change in the mix in the portfolio over the period 2022 to '26 moving to about 75% of the revenues coming from Specialty and Vaccines, moving to 25% coming from the General Medicines portfolio. And that mix change is an important part of the change overall.

就通過銷售商品成本帶來的生產力而言，這部分是由收入驅動的。因此，我們看到 2022 年至 26 年間投資組合的組合發生了變化，大約 75% 的收入來自專業和疫苗，而 25% 的收入來自普通藥物組合。這種混合變化是整體變化的重要組成部分。

Now when you talk about geographic mix, we remain broadly stable to where we are. So we've got about 40% of our revenues in the U.S. now. By '26, we'd expect about 40% of revenues to be U.S. as well from a biopharma perspective. But that change in mix of new -- of specialty medicines and vaccines to 75% versus 25% is an important component of the overall gross margin story, notwithstanding the continued delivery of productivity and synergies coming through the supply chain. So those are key dynamics that are coming through there.

現在，當您談論地理組合時，我們大致上保持穩定。所以我們現在有大約 40% 的收入來自美國。到 26 年，從生物製藥的角度來看，我們預計大約 40% 的收入將來自美國。但是，儘管通過供應鏈持續提供生產力和協同效應，但將新的特殊藥物和疫苗組合從 25% 變為 75% 的變化是整體毛利率的重要組成部分。因此，這些是正在經歷的關鍵動力。

We're also having a bit of a 1-year recovery of COVID T&A. I know we're keeping costs very much under control on that, but we are expecting to go back (inaudible).

我們也對 COVID T&A 進行了為期 1 年的恢復。我知道我們在很大程度上控制了這方面的成本，但我們預計會回去（聽不清）。

Absolutely, but very much within the guidance that we provided today, Emma.

絕對可以，但在我們今天提供的指導範圍內，艾瑪。

The next one is coming from the line of Steve Scala from Cowen.

下一個來自 Cowen 的 Steve Scala。

It looks as though the ContRAst 1, 2 and 3 trials of otilimab are well past their primary completions. They have conventional endpoints, so there's no events to wait for. So is the data in-house and how I have to say you do sound more confident today than you've been in the past? Or is there a delay? And why won't the filing be earlier than 2023?

看起來 otilimab 的 ContRAst 1、2 和 3 試驗已經遠遠超過了他們的初步完成。他們有傳統的端點，所以沒有要等待的事件。內部數據也是如此，我怎麼說你今天聽起來比過去更有信心？還是有延遲？為什麼不早於 2023 年提交申請？

Thanks, Steve. No, I have not seen the data. Love to see the data, but I have not. And the reason is -- and you're absolutely right, that it's a 12-week endpoint. It's not event-driven. So that shouldn't be the problem. The issue is the data remains blinded with all these studies to -- for the 52-week follow-up because of the interest in secondary endpoints of being -- having the active inverter phase of the program. So in order to maintain the integrity of the trial at line for a longer period of time.

謝謝，史蒂夫。不，我沒有看到數據。喜歡看數據，但我沒有。原因是——你完全正確，這是一個 12 週的終點。它不是事件驅動的。所以這應該不是問題。問題是所有這些研究的數據仍然是盲目的——對於 52 週的隨訪，因為對存在的次要終點感興趣——具有該計劃的有源逆變器階段。所以為了保持試行的完整性，可以在更長的時間內上線。

Question is coming from the line of Andrew Simon Baum from Citi.

問題來自花旗的 Andrew Simon Baum。

A question on BCMA to 2 parts. Firstly, DREAMM-5, your -- yes, can you hear me?

關於 BCMA 的問題分為 2 部分。首先，DREAMM-5，你的——是的，你能聽到我說話嗎？

Yes, we can hear you.

是的，我們可以聽到你的聲音。

Hello?

你好？

Hi, Andrew, we can hear you. Yes.

嗨，安德魯，我們可以聽到你的聲音。是的。

Hello? Hello?

你好？你好？

Right.

對。

Terrific. Terrific. I can hear you too. So here we go. The questions on BCMA and DREAMM-5 with the gamma secretase, you recently expanded that cohort. It's an open-label trial. GSK has of late talked more about scheduling dose fractionation and less focus on the benefits of GSI. Given that is open label, given you've expanded the cohort, perhaps you could share what you're seeing? And then secondly, also on BCMA, there's been some recent data published with the [CAR T] fee suggesting that BCMA CAR-Ts were associated with Parkinson's type syndrome with BCMA expression on substantial nigra. So the question is, do you have any evidence that belantamab crosses the blood-brain barrier? I'll stop there.

了不起。了不起。我也能聽到你的聲音。所以我們開始吧。關於 BCMA 和 DREAMM-5 與 gamma 分泌酶的問題，您最近擴展了該隊列。這是一個開放標籤試驗。葛蘭素史克最近更多地談到了安排劑量分割，而較少關注 GSI 的好處。鑑於這是開放標籤，鑑於您已經擴大了隊列，也許您可以分享您所看到的？其次，同樣在 BCMA 上，最近有一些數據與 [CAR T] 費用一起發布，表明 BCMA CAR-T 與帕金森型綜合徵相關，BCMA 在大量黑質上表達。所以問題是，你有任何證據表明 belantamab 可以穿過血腦屏障嗎？我會停在那裡。

All right. Hal?

好的。哈爾？

Well, thank you, Andrew. Let me try to address that. It's a really interesting question about the Parkinson's. We have no evidence to suggest, and I'm reasonably confident that it doesn't, the antibody crosses the blood-brain barrier. So to the extent that it is a nontarget effect, we're not observing that clinically, and I wouldn't expect us to. I can look into a little bit more detail about that later, but I'm pretty confident it's not crossing the blood brain barrier. But it's an interesting point you make about the CARs.

好吧，謝謝你，安德魯。讓我試著解決這個問題。這是關於帕金森氏症的一個非常有趣的問題。我們沒有證據表明，我有理由相信它不會，抗體穿過血腦屏障。因此，就它是一種非目標效應而言，我們沒有在臨床上觀察到這一點，我也不希望我們這樣做。稍後我可以詳細了解一下，但我很有信心它不會越過血腦屏障。但這是你對 CAR 提出的一個有趣的觀點。

As you know, the rationale for the combination of the GSI (inaudible) it should be able to increase the density of BCMA on the plasma cells or maybe any cell, but the plasma cells of interest and therefore, be able to obtain responses at lower doses. And we hope that at lower doses, there would be less ocular toxicity. It's 1 of the 4 levers that we're using to try to improve the benefit risk ratio, and I'll go into the other 3 in a second.

如您所知，GSI 組合的基本原理（聽不清）應該能夠增加漿細胞或任何細胞上 BCMA 的密度，但感興趣的漿細胞因此能夠在較低的情況下獲得響應劑量。我們希望在較低劑量下，眼睛毒性會更小。這是我們用來嘗試提高收益風險比的 4 個槓桿中的一個，我將在稍後介紹其他 3 個。

We have seen some open-label data. And as we said, it is encouraging. It's small numbers, and I think we've all seen examples where small numbers of encouraging data doesn't always translate, but the data was definitely encouraging enough that we moved into a randomized setting. So using the DREAMM-5 platform to begin a more robust program where we both have a larger number of patients, but also a control arm to make sure that it's not confounded by baseline covariance that can occasionally happen. But I can say that our optimism was based on seeing data. And we -- as you know, we're using doses at the milligrams per kilogram level, which at least in the DREAMM-1 and 2 studies, was inactive. So we think that that's a reasonable way of assessing our level of optimism.

我們已經看到了一些開放標籤數據。正如我們所說，這是令人鼓舞的。這是很小的數字，我想我們都看到了一些例子，其中少量的令人鼓舞的數據並不總是能轉化，但這些數據絕對令人鼓舞，以至於我們進入了隨機環境。因此，使用 DREAMM-5 平台開始一個更強大的計劃，我們既有更多的患者，也有一個控制臂，以確保它不會被偶爾發生的基線協方差混淆。但我可以說，我們的樂觀是基於看到數據。而且我們 - 如您所知，我們使用的劑量是毫克每公斤，至少在 DREAMM-1 和 2 研究中，這是不活躍的。所以我們認為這是評估我們樂觀程度的合理方式。

But midyear this year, we should have a much more robust data set, hopefully, with some control patients and be able to be clear with the value that this could provide to move into front line. As you know, the other 3 levers that we're looking at to optimize this program are to see if the combination of BLENREP with standard of care, whether it be with pomalidomide or DARZALEX or Velcade or various other standard of care reagents would allow us to be able to reduce the dose to further maximize its benefit risk. We're also looking at something relatively simple, which is in the phase Pivotal DREAMM-2 study.

但今年年中，我們應該有一個更強大的數據集，希望有一些控制患者，並且能夠清楚這可以為進入一線提供的價值。如您所知，我們正在考慮優化該計劃的其他 3 個槓桿是查看 BLENREP 與護理標準的組合，無論是與泊馬度胺、DARZALEX 或 Velcade 還是各種其他護理標準試劑的組合，都可以讓我們能夠減少劑量以進一步最大化其受益風險。我們也在研究一些相對簡單的東西，這是在 Pivotal DREAMM-2 階段的研究中。

The protocol had dose holding when Grade 3 ocular tox was identified or ability to reduce Grade 3 and above ocular toxicity is limited if that's when you hold the dose. Given the profound efficacy that we're observing in multiple different trials now, we've decided to hold the dose when we're seeing grade 2 ocular tox, which in theory and actually observed data from ASH, suggests that the oculotox is going down further. And maybe even the most important of all these, who knows, is going to be that we're altering and exploring different schedules.

當發現 3 級眼部毒性時，該方案具有劑量保持，或者如果您保持劑量，則降低 3 級及以上眼部毒性的能力是有限的。鑑於我們現在在多個不同試驗中觀察到的顯著療效，我們決定在看到 2 級眼部毒素時保持劑量，從理論上和實際觀察到的 ASH 數據表明，眼部毒素正在下降更遠。也許所有這些中最重要的，誰知道呢，將是我們正在改變和探索不同的時間表。

So as you know, in DREAMM-2 in the approved dose of (inaudible) and later lines of therapy was using 2.5 mg per kg Q3 weeks. We're looking at Q4, Q6 and Q8 dosing, doses of 2.5, 1.9 and even lower. And seeing if Cmax versus trough is going to have an impact on both efficacy and hopefully reduce ocular type. So those 4 levers, if you will, all being studied independently and the ability to use them as modules and combine them to move us into third, second, which we're reasonably confident in and maybe even frontline, we'll have data midyear to help you understand that.

如您所知，在 DREAMM-2 中，批准劑量（聽不清）和後來的治療線是使用 2.5 mg/kg Q3 週。我們正在研究 Q4、Q6 和 Q8 的劑量，劑量分別為 2.5、1.9 甚至更低。看看 Cmax 與穀值是否會對療效產生影響，並有望減少眼型。所以這 4 個槓桿，如果你願意的話，都是獨立研究的，並且能夠將它們用作模塊並將它們組合起來，使我們進入第三、第二，我們對此有相當的信心，甚至可能是前線，我們將在年中獲得數據幫助您理解這一點。

Next one is coming from Laura Sutcliffe from UBS.

下一位來自瑞銀的 Laura Sutcliffe。

Could we go back to HIV, please? There's been some commentary in recent days in Gilead talking about a tougher first quarter 2022 than 2021 based on co-pay scheme reset in the U.S. and other gross-to-net dynamics. Is there anything we should be thinking about along those lines for your portfolio in terms of it being more aggressive this year than it was last year? And then just related, given the wider importance of the Access to Medicines piece at group level, is there anything you see changing on your ESG profile or external rankings, whichever ones you consider to be most meaningful when consumer leaves the group later this year?

請問我們可以回到艾滋病毒嗎？最近幾天，吉利德（Gilead）有一些評論稱，基於美國重新設定的共同支付計劃和其他毛淨額動態，2022 年第一季度將比 2021 年更艱難。就今年比去年更具侵略性而言，我們應該為您的投資組合考慮哪些方面？然後只是相關的，考慮到“藥品獲取”部分在集團層面的更廣泛重要性，您是否看到您的 ESG 概況或外部排名有任何變化，無論您認為今年晚些時候消費者離開集團時哪個最有意義？

Thanks. Well, on the broader ESG and then we'll come to (inaudible) to see us continuing to seek, make leadership in the SGA priority for GSK, and we will be updating our reporting on that, frankly, to make it ever simpler, more transparent and easier for us to be held to account across the 6 key areas we've identified as priority for ESG, whether that be in access environment, in diversity and inclusion. And so we're really looking forward to discussing that with you.

謝謝。好吧，在更廣泛的 ESG 上，然後我們將（聽不清）看到我們繼續尋求，在 GSK 的 SGA 優先事項中發揮領導作用，坦率地說，我們將更新我們的報告，以使其變得更簡單，在我們確定為 ESG 優先事項的 6 個關鍵領域（無論是在准入環境、多樣性和包容性方面），我們都更透明、更容易被追究責任。因此，我們非常期待與您討論這個問題。

You'll also be familiar with the fact that this is, I would say, a focused level it's included in the accountabilities from an incentive point of view as well. It really is something that has long been at the core of who we are as a company. It never replaces TSR, but I'm hoping that we are able to continue to get the recognition for our very much leading rankings we have, but also transparency and simplicity of reporting in a way that is, of course, validated by third parties as opposed to us just making our own homework. But maybe I'll come back to Deborah, please, for the HIV question.

你也會熟悉這樣一個事實，我想說，從激勵的角度來看，它也是包含在問責制中的一個重點級別。這確實是我們作為一家公司長期以來的核心。它永遠不會取代 TSR，但我希望我們能夠繼續獲得認可，因為我們擁有非常領先的排名，而且報告的透明度和簡單性也得到了第三方的認可。反對我們只做自己的功課。但也許我會回到黛博拉，請，關於艾滋病毒問題。

Thanks, Laura. So if I think about the prep market and treatment, 2 separate markets. So in the treatment market, it continues to be guideline-driven for choice and accesses at the core. In the prep market, it's a little bit different to that. And we see that market as continuing to be relatively stable. Obviously, the Build Back Better Bill will affect the whole industry. So let's see how that plays out. But in terms of what -- if you assume that's taken to one side, the treatment market looks fairly stable and continues to be guideline-driven choice and access at the core.

謝謝，勞拉。因此，如果我考慮準備市場和治療，兩個獨立的市場。因此，在治療市場中，核心選擇和訪問仍然是由指南驅動的。在預科市場，情況與此略有不同。我們認為該市場繼續保持相對穩定。顯然，“重建更好的法案”將影響整個行業。那麼讓我們看看結果如何。但就什麼而言 - 如果你假設這是一方面，治療市場看起來相當穩定，並且繼續以指南驅動的選擇和訪問為核心。

In the prep market, it's a little bit different to that. So obviously, we've got a generic of Truvada in the market. Gilead has moved quite a lot of the market away from Truvada into Descovy, but I think that's taken, obviously, some negotiation with payers to make that happen. And we're in dialogue with payers at the moment over ensuring that we can get broad access to Apretude at a price that rewards our innovation. So I think you should look at treatment and prep as a little bit separate.

在預科市場，情況與此略有不同。很明顯，我們在市場上有了特魯瓦達的仿製藥。吉利德已經將相當多的市場從 Truvada 轉移到了 Descovy，但我認為這顯然需要與付款人進行一些談判才能實現。我們目前正在與付款人進行對話，以確保我們能夠以獎勵我們創新的價格廣泛使用 Apretude。所以我認為你應該把治療和準備看作是分開的。

But in the main, the treatment market is 5x bigger than the prep market. So the core of where our revenue and our profit comes from remains stable.

但總的來說，治療市場比預備市場大 5 倍。因此，我們的收入和利潤來源的核心保持穩定。

And the other core is having truly differentiated medicines and medicines to get approved and stopped in their trials for being so significantly better than existing standard of care deliver a value that is worth paying for.

另一個核心是擁有真正差異化的藥物和在試驗中獲得批准和停止的藥物，因為它們比現有的護理標準好得多，提供了值得付出的價值。

Absolutely.

絕對地。

Next one is coming from the line of Seamus Fernandez from Guggenheim.

下一位來自古根海姆的 Seamus Fernandez。

So my question is actually on HBV. Just wondered how -- if you could give us your thoughts on the HBV ASO versus antibody-based approaches as well as just your general thoughts on how we're likely to ultimately see a real break in HBV cures? Is that going to require a combination of a treatment-based approach followed by a vaccine in your view? Or when we see these data later this year, do you think that either an ASO or perhaps RNAi-based approach will really be viewed as the preferred way to then pursue cures?

所以我的問題實際上是關於 HBV。只是想知道如何 - 如果您能告訴我們您對 HBV ASO 與基於抗體的方法的看法，以及您對我們最終可能如何看到 HBV 治癒的真正突破的一般看法？在您看來，這是否需要結合基於治療的方法和疫苗？或者當我們在今年晚些時候看到這些數據時，您是否認為 ASO 或基於 RNAi 的方法真的會被視為尋求治癒的首選方法？

Yes. Thanks for the question. It's really good question. It's really hard to predict the future on this. But it is likely that what we'll see with the ASOs is a couple of things. First, I think it's pretty clear that not all ASOs are behaving the same way. So I think over the next 6 to 12 months, we'll get more clarity on the value of the various approaches of ASOs, GalNAc or unmodified. I think we'll get a good sense, and I'm optimistic from our 2Adata that the ASO approach will deliver efficacy as it relates to lowering the surface antigen.

是的。謝謝你的問題。這真是個好問題。在這方面真的很難預測未來。但很可能我們將在 ASO 中看到幾件事。首先，我認為很明顯並非所有 ASO 的行為方式都相同。所以我認為在接下來的 6 到 12 個月內，我們將更清楚地了解 ASO、GalNAc 或未修改的各種方法的價值。我認為我們會很清楚，我對我們的 2Adata 持樂觀態度，即 ASO 方法將提供與降低表面抗原相關的功效。

One of the hypotheses is that this -- as far as it makes a massive amount of surface antigen and one compelling hypothesis that's pretty well supported from preclinical data. that, that overwhelms the T cells and it results in T cell exhaustion. And that by lowering the HBV surface antigen levels, the immune system may be able to kick in.

其中一個假設是——就它產生大量的表面抗原和一個令人信服的假設而言，這一假設得到了臨床前數據的充分支持。這會壓倒 T 細胞並導致 T 細胞衰竭。通過降低 HBV 表面抗原水平，免疫系統可能能夠發揮作用。

My guess is that, that will work in some people, but probably a very small minority. And what's going to be needed is combinations, whether that's a combination with a (inaudible) or possibly even something like a checkpoint blockade like PD-1 or maybe even a sting agonist, things that are going to increase the interferon production from the cooper cells and other cells responsible for the (inaudible).

我的猜測是，這將適用於某些人，但可能是極少數人。需要的是組合，無論是與（聽不清）或什至可能是像 PD-1 這樣的檢查點封鎖，甚至可能是刺痛激動劑的組合，都會增加庫珀細胞產生的干擾素和其他負責（聽不清）的細胞。

I do think, though, that in the end, after we figure all this out, and hopefully, we'll have some compelling data midyear with the CLEAR study that we'll be able to embark on these combination studies in a thoughtful manner and ultimately reduce the really enormous burden, 250 million people living with chronic hep B and, as I mentioned, 90,000 people dying from it annually and if we can make a dent in the functional cure rate, which is a very high bar. That will be one of the more significant advances in medicine.

不過，我確實認為，最終，在我們弄清楚這一切之後，並希望我們將在年中通過 CLEAR 研究獲得一些令人信服的數據，我們將能夠以深思熟慮的方式開始這些組合研究，並且最終減輕真正巨大的負擔，2.5 億慢性乙型肝炎患者，正如我所提到的，每年有 90,000 人死於它，如果我們能夠降低功能性治愈率，這是一個非常高的標準。這將是醫學上更重要的進步之一。

The next one is coming from the line of Kerry Holford from Berenberg.

下一個來自貝倫貝格的 Kerry Holford。

Just a follow-up on RSV on older adults, please. How you mentioned targeting the June ASB meeting. So I guess you're working on the assumption of a launch next year. And I would just like to understand what gives you the confidence that the regulators accept it to package from 1 RSV-C only, given your competitor studies will continue further? Is there a risk that the regulators want to see more data across more seasons before moving to approve a vaccine here? And do you think that decision will ultimately be influenced by the clinical efficacy you and your peers deliver?

請對老年人進行 RSV 的後續行動。您如何提到針對 6 月的 ASB 會議。所以我猜你正在研究明年推出的假設。而且我想了解是什麼讓您有信心監管機構接受它僅從 1 RSV-C 包裝，因為您的競爭對手研究將繼續進一步？在批准疫苗之前，監管機構是否存在希望在更多季節看到更多數據的風險？您是否認為該決定最終會受到您和您的同行提供的臨床療效的影響？

Thanks, Kerry. I think we're pretty confident in our strategy. But of course, any approval and any recommendation for use is going to depend on the risk benefit. We're expecting a reasonably high success rate and effectiveness rate for this vaccine and being able to show it works well in the various subgroups of interest as well as determining whether this is going to be effective in an equally significant way across the season. In other words, how effective the duration of efficacy relates.

謝謝，克里。我認為我們對我們的戰略非常有信心。但當然，任何批准和任何使用建議都將取決於風險收益。我們預計這種疫苗的成功率和有效率相當高，並且能夠證明它在各種感興趣的亞組中效果很好，並確定這是否會在整個賽季中以同樣重要的方式有效。換句話說，效力持續時間的有效性如何相關。

So when we have all that data, I think we'll be able to have a better sense, but we're pretty confident in our strategy of the trial design, the sample size, the effect rate and the risk benefit that, that would endure. I should also mention that, of course, that the ASO is something that we have enormous amount of experience with in a very, very large safety database with. So it's really going to be driven by the efficacy and probably viewed by ASIP in aggregate all the data as well as how the regulators will be reaching individual company.

因此，當我們擁有所有這些數據時，我認為我們將能夠有更好的感覺，但我們對我們的試驗設計策略、樣本量、有效率和風險收益非常有信心，這將忍受。當然，我還應該提到，ASO 是我們在一個非常非常大的安全數據庫中擁有大量經驗的東西。因此，它實際上將由功效驅動，並且可能由 ASIP 綜合所有數據以及監管機構將如何接觸個別公司來看待。

Question is coming from the line of Mark Purcell from Morgan Stanley.

問題來自摩根士丹利的 Mark Purcell。

Just again on RSV, or auto, so getting a bit perspective. I wonder if you could sort of help us understand how we can assess whether the ASO1 adjuvant will provide a potential durability advantage from the initial data sets, your own data sets, so Renoir and Evergreen. What should we be looking out for which suggests you might have a sort of T-cell restoration benefit? And then just a related question. Are there any IP considerations around the prefusion F subunit target? Clearly, you were a first-mover when it came to HPV and you secured a royalty stream. Is there something such that we should think that, that situation could occur with RSV?

再次在 RSV 或汽車上，所以有點觀點。我想知道您是否可以幫助我們了解我們如何評估 ASO1 佐劑是否會從初始數據集、您自己的數據集，如 Renoir 和 Evergreen 中提供潛在的耐用性優勢。我們應該注意什麼，這表明您可能有某種 T 細胞恢復益處？然後只是一個相關的問題。是否有圍繞預融合 F 亞基目標的任何 IP 考慮？顯然，在 HPV 方面，您是先行者，並且獲得了版稅流。有沒有我們應該認為 RSV 會發生這種情況的事情？

Yes. Thanks, Mark. Why don't I tackle the first part. And I don't think there's any IP issues that we're unaware of. But I'll let Roger jump in if he knows something I don't. I think it's going to be challenging to figure out the impact of the adjuvant on duration as it relates to multiyear because, of course, well, we won't have a multiyear and back when you look at Shingrix, it obviously took 8 years to figure out that it worked so well for 8 years. I do think there is going to be hints potentially. One could look forward to be underpowered for these, but I think they might be directionally useful.

是的。謝謝，馬克。我為什麼不處理第一部分。而且我認為沒有任何我們不知道的知識產權問題。但如果他知道我不知道的事情，我會讓羅傑加入。我認為要弄清楚佐劑對持續時間的影響與多年期有關，這將是一項挑戰，因為當然，當您查看 Shingrix 時，我們不會有多年期和返回，顯然需要 8 年才能發現它運行了 8 年這麼好。我確實認為會有潛在的暗示。人們可能會期待這些功能不足，但我認為它們可能在方向上有用。

First of all is the point estimate of benefit greater than other trials. I think that's one thing to look for. That would suggest that the adjuvant is doing something unique. It could also be that in subgroups, particularly the older 75 and particularly immunosuppressed patients, one might see a signal that looks more prominent than nonadjuvanted. That might give you a signal. And as I said a few minutes ago, there is a way of looking at the duration of efficacy of the season.

首先是比其他試驗更大的收益點估計。我認為這是要尋找的一件事。這表明佐劑正在做一些獨特的事情。也可能是在亞組中，特別是年齡較大的 75 歲和特別是免疫抑制患者，人們可能會看到一種看起來比非輔助治療更突出的信號。這可能會給你一個信號。正如我幾分鐘前所說，有一種方法可以查看本賽季效力的持續時間。

So if the efficacy with a non-adjuvanted vaccine, for instance, is pretty significant in the beginning of the season, but wanes during the end of the season, and for instance, ours would have a treatment effect is impressive and constant over that period of time, one might be more confident that there could be a duration effect one looks longer. But at the end of the day, we're going to have to look for longer-term follow-up. And we have studies already underway that I'll explore then. Roger, did you want to add any?

因此，例如，如果使用非佐劑疫苗的效果在賽季開始時非常顯著，但在賽季結束時會減弱，例如，我們的治療效果會令人印象深刻且在此期間保持不變隨著時間的推移，人們可能會更有信心認為可能會出現持續時間更長的效果。但歸根結底，我們將不得不尋找更長期的後續行動。我們已經進行了一些研究，我將在那時進行探索。羅傑，你想添加任何東西嗎？

Yes. Just on the IP, there's no IP restrictions on the pre-F nor is there any IP direct ownership from our perspective that would generate income. So that's not something which we have be thinking of or worrying about .

是的。就 IP 而言，pre-F 沒有 IP 限制，從我們的角度來看，也沒有任何 IP 直接所有權會產生收入。所以這不是我們一直在考慮或擔心的事情。

Okay. I'm not sure if we've got time to go through one more question. And we have one more question. So maybe, Brian?

好的。我不確定我們是否有時間再回答一個問題。我們還有一個問題。所以也許吧，布賴恩？

Our last question for today's call comes from Peter Welford from Jefferies.

我們今天電話會議的最後一個問題來自 Jefferies 的 Peter Welford。

Just a question just on RSV back again in the older adults. Can I just ask -- when we think about the COVID data, have we all been spoiled the hospitalization and decreases that we saw there at 90% plus in some cases. And perhaps could you give us some sort of idea of what we should be thinking about for the RSV Phase III with regards to what is a reasonable higher reduction in hospitalization? Is inosevumab, 80% or so reduction, a sensible sort of ballpark that we should regard as clinically meaningful.

只是一個關於老年人的 RSV 問題。我可以問一下——當我們考慮 COVID 數據時，我們是否都被住院治療和在某些情況下看到的 90% 以上的住院率所破壞。也許你能給我們一些想法，關於我們應該為 RSV 第三階段考慮什麼是合理的更高的住院率？ inosevumab 是否減少了 80% 左右，是一種我們應該認為具有臨床意義的合理範圍。

And perhaps just a comment, I think you probably should probably an award for sort of the massive of understatement. From my calculation, it seems as though your strong double-digit growth is probably over 40% machine grid. Can you just remind us if the GBP 2.5 billion, if that's roughly where I get to from your guidance, is entirely can be met with existing manufacturing? And should we then consider future growth from that? Again, are you confident that you can sustain that level of growth and that level of demand with your existing capacity that you have without the new facility?

也許只是一個評論，我認為你可能應該為某種輕描淡寫的東西頒獎。根據我的計算，您強勁的兩位數增長似乎可能超過 40% 的機器網格。你能否提醒我們，如果這大約是我從你的指導中得到的 25 億英鎊，是否完全可以用現有的製造業來滿足？然後我們應該考慮未來的增長嗎？同樣，您是否有信心在沒有新設施的情況下以現有產能維持這種增長水平和需求水平？

Yes. So let me be extremely -- well, utterly unequivocal. We are not supply-constrained, and we're very confident on doubling our sales from the 2020 levels in terms of the outlook that we gave the update last year. We feel very good about getting a bounce back. Obviously, there's been a bit of COVID disruptions. But as Luke outlined, the momentum is very good. I don't know, Hal, if there's anything further we want to add.

是的。所以讓我非常 - 好吧，非常明確。我們不受供應限制，我們非常有信心將我們的銷售額從 2020 年的水平翻一番，就我們去年給出的更新展望而言。我們對反彈感到非常高興。顯然，有一些 COVID 中斷。但正如盧克所概述的那樣，勢頭非常好。我不知道，哈爾，我們是否還有什麼要補充的。

No, I'll just say that, of course, it's very hard to predict the efficacy. But as we look at our own immunogenic data and the aggregate packages that have been presented, I think we've -- and in discussions with clinicians, we're pretty confident that any effect, more than 50% is clinically meaningful. An effect, greater than 70%, is a very good response and it will be a very successful vaccine. And should we get efficacy above 80%, that's outstanding.

不，我只是說，當然，很難預測療效。但是當我們查看我們自己的免疫原性數據和已經提交的匯總包時，我認為我們已經 - 在與臨床醫生的討論中，我們非常有信心任何效果，超過 50% 具有臨床意義。大於 70% 的效果是非常好的反應，這將是一種非常成功的疫苗。如果我們的功效達到 80% 以上，那就太棒了。

Great. Well, with that, thank you very much, everybody. We shall look forward to gathering with some of you over the next few days. And we're really looking forward to an extremely exciting year ahead for GSK. Whether that's doing everything that we said we were going to do, the delivery of the step-change in growth, reading out on some of these very exciting pipeline milestones, continuing to accelerate the execution, all that we already have in hand and plan for very competitive execution of what's to come, and of course, the tremendous unlock of value that's going to come with the creation of a completely unique FTSE leading world leader dedicated to consumer health care.

偉大的。好了，到此，非常感謝大家。我們期待在接下來的幾天裡與你們中的一些人相聚。我們真的很期待葛蘭素史克在接下來的一年中非常激動人心。無論是在做我們說過要做的所有事情，實現增長的階梯式變化，閱讀其中一些非常令人興奮的管道里程碑，繼續加速執行，所有我們已經掌握和計劃的事情非常有競爭力的未來執行，當然，隨著創建一個致力於消費者醫療保健的完全獨特的 FTSE 領先的世界領導者，將帶來巨大的價值釋放。

And I know Brian is enormously looking forward to the long Q&A session on that at the end of this month. Thanks, everybody. Catch up soon.

我知道布賴恩非常期待本月底就此舉行的長長的問答環節。謝謝大家。很快趕上。