Vaxcyte Inc (PCVX) 2023 Q4 法說會逐字稿

Good afternoon, everyone. My name is Bo, and I will be your conference operator today. At this time, I would like to welcome everyone to the Vaxcyte fourth-quarter and full year 2023 financial results conference call. (Operator Instructions) And just a reminder, today's call is being recorded.

大家下午好。我叫 Bo，今天我將擔任你們的會議操作員。此時，我歡迎大家參加 Vaxcyte 第四季和 2023 年全年財務業績電話會議。（操作員說明）提醒一下，今天的通話正在錄音。

Now at this time, I'll turn things over to Mr. Andrew Guggenhime, President and Chief Financial Officer of Vaxcyte. Please go ahead, sir.

現在這個時候，我會把事情交給 Vaxcyte 總裁兼財務長 Andrew Guggenhime 先生。請繼續，先生。

Thank you, operator, and good afternoon, everyone. I'd like to welcome you to Vaxcyte's earnings conference call to discuss our 2023 results and to provide a business update. I'm joined today by our Chief Executive Officer, Grant Pickering, and our Executive Vice President and Chief Operating Officer, Jim Wassil.

謝謝接線員，大家下午好。歡迎您參加 Vaxcyte 的收益電話會議，討論我們 2023 年的表現並提供業務更新。今天，我們的執行長格蘭特·皮克林 (Grant Pickering) 和執行副總裁兼營運長吉姆·瓦西爾 (Jim Wassil) 也加入了我的行列。

Earlier this afternoon, we issued a news release announcing our results. Copies of this and our other news releases for the corporate presentation and SEC filings can be found in the Investors and Media section of our website.

今天下午早些時候，我們發布了一份新聞稿，宣布了我們的結果。您可以在我們網站的投資者和媒體部分找到本新聞稿以及我們公司簡報和 SEC 備案的其他新聞稿的副本。

Before we begin, I'd like to remind you that during this call, we'll be making certain forward-looking statements about Vaxcyte, which are subject to various risks, uncertainties and other factors that could cause actual results to differ materially from those referred to in any forward-looking statements. For a discussion of the risks and uncertainties associated with these statements. Please see our press release issued today as well as our most recent filings with the SEC, including the risk factors set forth in our Form 10-K for the year ended December 31, 2023, and any subsequent reports filed with the SEC.

在我們開始之前，我想提醒您，在這次電話會議中，我們將做出一些有關Vaxcyte 的前瞻性陳述，這些陳述受到各種風險、不確定性和其他因素的影響，可能導致實際結果與預期結果有重大差異任何前瞻性陳述中提及。討論與這些陳述相關的風險和不確定性。請參閱我們今天發布的新聞稿以及我們最近向 SEC 提交的文件，包括截至 2023 年 12 月 31 日的年度 10-K 表格中列出的風險因素，以及向 SEC 提交的任何後續報告。

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

這樣，我會將電話轉給格蘭特·皮克林。授予？

Thanks, Andrew, and all of you on the call and webcast. Thank you for joining us today. 2023 was another remarkable year for Vaxcyte, officially marking our 10th year of thoughtful and methodical research and development by the entire Vaxcyte team and our partners. We are driven by our mission to prevent or treat infections caused by bacterial diseases, including invasive pneumococcal disease or IPD. This past year, we continued to make significant strides in advancing our potentially best-in-class pneumococcal conjugate vaccines or PCVs, VAX-24, our lead 24 valent candidate and VAX-31, our next-generation 31 valent candidate. And we remain focused on providing the broadest spectrum of coverage against IPD for both adults and children.

謝謝安德魯以及參加電話會議和網路廣播的所有人。感謝您今天加入我們。 2023 年對 Vaxcyte 來說又是非凡的一年，正式標誌著整個 Vaxcyte 團隊和合作夥伴深思熟慮、有條不紊的研究和開發的第十個年頭。我們的使命是預防或治療細菌性疾病引起的感染，包括侵襲性肺炎球菌疾病或 IPD。去年，我們在開發潛在的同類最佳肺炎球菌結合疫苗或 PCV、我們的主要 24 價候選疫苗 VAX-24 和我們的下一代 31 價候選疫苗 VAX-31 方面繼續取得重大進展。我們仍然致力於為成人和兒童提供最廣泛的 IPD 覆蓋範圍。

Last year was highlighted by the successful completion of our VAX-24 adult Phase 2 program. Following our stellar initial crop of concept data in late 2022 in adults aged 50 to 64, we reported data in April 2023 from a separate Phase 2 study in adults 65 and older that not only confirmed the prior proof-of-concept study results that showed even greater immune responses compared to Prevnar 20 on a relative basis. These data further validate the potential of our cell-free platform and carrier sparing approach to deliver broader-spectrum PCVs. The findings from our adult Phase 2 program support the potential best-in-class profile for VAX-24 and demonstrate how our novel cell-free technology platform has the capability to overcome the limitations of other conventional approaches. These results and the foundation we have carefully created have us well positioned to advance our PCV franchise to potentially disrupt what has consistently been a crucial vaccine class societally and financially.

去年的亮點是我們的 VAX-24 成人 2 期計劃的成功完成。繼2022 年底在50 至64 歲成年人中獲得了出色的初步概念數據後，我們於2023 年4 月報告了一項針對65 歲及以上成年人的單獨2 期研究的數據，該數據不僅證實了先前的概念驗證研究結果，相對而言，與 Prevnar 20 相比，免疫反應甚至更強。這些數據進一步驗證了我們的無細胞平台和載體保留方法提供更廣譜 PCV 的潛力。我們的成人第 2 期計畫的研究結果支持了 VAX-24 潛在的同類最佳特性，並證明了我們的新型無細胞技術平台如何克服其他傳統方法的局限性。這些結果和我們精心創建的基礎使我們處於有利地位，可以推進我們的 PCV 特許經營權，從而有可能顛覆一直在社會和經濟上至關重要的疫苗類別。

Following the VAX-24 adult Phase 2 program completion, we made important progress with regulators. This included a successful end of Phase 2 meeting with the FDA regarding the clinical design of the VAX-24 Phase 3 program as well as encouraging feedback on CMC-related matters as we plan for future potential BLA submissions.

隨著 VAX-24 成人第 2 階段計畫完成，我們與監管機構取得了重要進展。這包括與 FDA 就 VAX-24 第 3 期項目的臨床設計舉行的第 2 期會議的成功結束，以及在我們計劃未來潛在的 BLA 提交時鼓勵對 CMC 相關事項的反饋。

In addition to the positive developments for VAX-24, we were pleased to initiate the adult clinical program for VAX-31. With this important step, VAC-31 is now the broadest-spectrum PCV in the clinic. Following the FDA's acceptance of the adult IND, we initiated the Phase I portion of a Phase 1/2 study in adults 50 and older in November.

除了 VAX-24 的積極進展外，我們很高興啟動 VAX-31 的成人臨床計劃。透過這一重要步驟，VAC-31 現在成為臨床上最廣譜的 PCV。在 FDA 接受成人 IND 後，我們於 11 月啟動了 50 歲及以上成人的 1/2 期研究的 I 期部分。

The strong momentum of this study continued into 2024 as we announced the start of the Phase 2 portion in early January and completion of enrollment less than a month later. I'm incredibly proud of our many achievements, particularly across clinical, regulatory and manufacturing for our PCV programs. And we now look ahead to several important milestones. For the adult indication, our VAX-24 program is Phase 3 ready. And we are in the final stages of manufacturing the product needed for several of the potential Phase 3 studies, including the pivotal non-inferiority study.

這項研究的強勁勢頭持續到 2024 年，我們在 1 月初宣布開始第二階段部分，並在不到一個月後完成入組。我對我們的許多成就感到無比自豪，特別是在我們的 PCV 項目的臨床、監管和製造方面。現在我們展望幾個重要的里程碑。對於成人適應症，我們的 VAX-24 計畫已做好第 3 階段的準備。我們正處於生產幾項潛在的第三階段研究（包括關鍵的非劣效性研究）所需產品的最後階段。

In advance of the potential initiation of this VAX-24 study in the second half of this year, we expect to announce the top line safety, power ability, and immunogenicity data from our VAX-31 adult Phase 1/2 study in the third quarter. This timing and the overlapping timeline for the completion of the VAX-24 and VAX-31 adult Phase 3 studies provide us the opportunity to make a strategic decision regarding which adult program when we'll move into Phase 3 following the VAX-31 data readout. If we advance VAX-24, we intend to initiate the pivotal non-inferiority study in the second half of this year and the balance of the Phase 3 studies, which are shorter in duration than the non-inferiority study in 2025 and 2026.

在今年下半年可能啟動這項 VAX-24 研究之前，我們預計將在第三季公佈我們的 VAX-31 成人 1/2 期研究的主要安全性、功效和免疫原性數據。這個時間安排以及完成 VAX-24 和 VAX-31 成人第 3 階段研究的重疊時間表使我們有機會就在 VAX-31 數據讀出後進入第 3 階段的成人項目做出戰略決策。如果我們推進VAX-24，我們打算在今年下半年啟動關鍵的非劣效性研究，並在2025年和2026年啟動比非劣效性研究持續時間更短的其餘3期研究。

If we advance VAX-31, we expect to initiate the full complement of the Phase 3 studies in 2025 and 2026. Regardless of which program we move forward, we expect to initiate the final Phase 3 studies in 2026. And subject to the results of these studies, submit a BLA shortly following the completion of the last study.

如果我們推進 VAX-31，我們預計將在 2025 年和 2026 年啟動全面的 3 期研究。無論我們推進哪個項目，我們都預計在 2026 年啟動最終的 3 期研究。根據這些研究的結果，在完成最後一項研究後不久提交 BLA。

VAX-24 remains a potential best-in-class candidate covering more serotypes than any pneumococcal vaccine on market or in US clinics today. And VAX-31 has the potential to further increase coverage to approximately 95% of IPD circulating in the US adult population.

VAX-24 仍然是潛在的同類最佳候選疫苗，其涵蓋的血清型比當今市場上或美國診所的任何肺炎球菌疫苗都要多。VAX-31 有潛力進一步將美國成年人口中 IPD 的覆蓋率提高到約 95%。

Beyond expanded disease protection, VAX-31 is designed to also maintain coverage of previously circulating strains that are currently contained via ongoing vaccination. This is critical since previously controlled strains have rebounded in prior instances where vaccines coverage was withdrawn. This puts us in a unique position relative to other sponsors who are applying the conventional PCV approach and are forced to make sacrifices in an attempt to cover newly circulating strains.

除了擴大疾病保護之外，VAX-31 還旨在維持對目前透過持續疫苗接種遏制的先前流行菌株的覆蓋範圍。這一點至關重要，因為先前控制的菌株在疫苗覆蓋範圍被撤銷的情況下已經反彈。與其他採用傳統 PCV 方法並被迫做出犧牲以試圖覆蓋新流行菌株的申辦者相比，這使我們處於獨特的地位。

We estimate that the adult pneumococcal vaccine market today is approximately $2 billion of the total $8 billion annual global market and is positioned to be the fastest-growing segment. Growth in the US market is expected to accelerate due to the potential shift in universal adult vaccination from age 65 down to 50, which would both expand the market and open up the adult regimen to a prime new schedule, nearing the infant market. Outside the US, we expect to see other countries begin to routinely recommend adult vaccination evidenced by the recent recommendation in Germany to vaccinate adults 60 and older.

我們估計，目前成人肺炎鏈球菌疫苗市場規模約為 20 億美元，佔全球年度市場總額 80 億美元，並且有望成為成長最快的部分。由於成人普遍接種疫苗的年齡可能從 65 歲降低到 50 歲，美國市場的成長預計將加速，這既會擴大市場，又會為成人治療方案開闢一個新的主要時間表，接近嬰兒市場。在美國以外，我們預計其他國家將開始常規建議成人接種疫苗，德國最近建議為 60 歲及以上成年人接種疫苗就是證明。

While the adult market is expected to grow significantly, the intent segment continues to represent the largest portion of the global pneumococcal vaccine market at an estimated $6 billion in sales annually. We believe VAX-24 has a potential best-in-class profile for this vital population, and we are thrilled to be nearing the completion of enrollment of the second and final stage of our VAX-24 infant Phase 2 study. Based on our progress, we expect the topline data from the primary immunization series by the end of the first quarter of 2025 with the topline booster data to follow by the end of that year.

雖然成人市場預計將大幅成長，但意向市場仍佔全球肺炎球菌疫苗市場的最大份額，每年銷售額估計為 60 億美元。我們相信 VAX-24 對於這一重要族群具有潛在的同類最佳特徵，我們很高興即將完成 VAX-24 嬰兒 2 期研究的第二階段和最後階段的招募。根據我們的進展，我們預計將於 2025 年第一季末獲得初級免疫系列的頂線數據，並於當年年底獲得頂線加強免疫數據。

In contrast to the adult program, the VAX-24 infant clinical program is substantially ahead of the VAX-31 infant program. And we intend to advance both of our PCV candidates in this population. We expect to provide guidance on the potential timing for a VAX-31 infant IND following the readout of the VAX-31 Phase 1/2 adult study later this year. Bringing the broadest PCVs to both infants and adults represents an opportunity to significantly reduce invasive disease across the entire population is what drives our efforts every day.

與成人計畫相比，VAX-24嬰兒臨床計畫大幅領先VAX-31嬰兒計畫。我們打算在這一人群中推廣我們的兩種 PCV 候選藥物。我們預計在今年稍後公佈 VAX-31 1/2 期成人研究結果後，就 VAX-31 嬰兒 IND 的潛在時機提供指導。為嬰兒和成人提供最廣泛的 PCV 代表了顯著減少整個人群侵襲性疾病的機會，這也是我們每天努力的動力。

Given the magnitude of the opportunity of our PCV franchise, we continue to invest in further solidifying our manufacturing foundation to enable robust large-scale manufacturing. These investments are intended to support the potential global commercialization of our PCVs for both the adult and infant populations. Our expanded relationship with Lonza and our decision to exercise our option on future Biopharma, both of which we announced late last year, are reflective of these efforts.

鑑於我們的 PCV 特許經營機會的巨大，我們將繼續投資，進一步鞏固我們的製造基礎，以實現穩健的大規模製造。這些投資旨在支持我們針對成人和嬰兒族群的 PCV 的潛在全球商業化。我們與 Lonza 擴大的關係以及對未來生物製藥公司行使選擇權的決定（這兩項決定都是我們在去年年底宣布的）都反映了這些努力。

In addition to our PCV franchise, we continue to advance our earlier-stage vaccine candidates, including VAX-A1 to prevent Group A Strep, VAX-PG to treat Periodontitis and VAX-GI to prevent dysentery and shigellosis. VAX-A1 and VAX-GI as well as our PCV programs target diseases that are significant contributors to antimicrobial resistance or AMR. AMR poses a serious global health at a no action is taken, drug-resistant diseases are expected by the WHO to be a leading cause of death by 2050. While AMR is a complex [crisis] that no single solution will fully address, vaccines represent an important part of the solution. We're proud to develop vaccines to help fight diseases that had become increasingly resistant to treatment with antibiotics. We look forward to sharing more updates on our earlier-stage pipeline over the course of the year.

除了我們的PCV 特許經營權之外，我們還繼續推進我們的早期候選疫苗，包括預防A 型鏈球菌的VAX-A1、治療牙周炎的VAX-PG 以及預防痢疾和志賀氏菌病的VAX- GI。VAX-A1 和 VAX-GI 以及我們的 PCV 計劃針對的是導致抗菌素抗藥性或 AMR 的重要疾病。如果不採取行動，抗菌素抗藥性將嚴重影響全球健康，世界衛生組織預計，到 2050 年，抗藥性疾病將成為主要死亡原因。雖然抗菌素抗藥性是一場複雜的[危機]，沒有任何單一的解決方案可以完全解決，但疫苗是解決方案的重要組成部分。我們很自豪能夠開發出疫苗來幫助對抗對抗生素治療越來越抗藥性的疾病。我們期待在這一年中分享我們早期研發管線的更多更新。

From a financial perspective, we substantially strengthened our balance sheet, raising approximately $545 million in net proceeds in a follow-on financing last April, and then added another $816 million earlier this month. Pro forma, after this most recent financing, we had over $2 billion in cash and investments as of year-end. This financial strength provides us the capital to fund the company through several important milestones over the next few years, which Andrew will highlight later.

從財務角度來看，我們大幅強化了資產負債表，在去年 4 月的後續融資中籌集了約 5.45 億美元的淨收益，並在本月稍早增加了 8.16 億美元。預計，在最近一次融資之後，截至年底，我們擁有超過 20 億美元的現金和投資。這種財務實力為我們提供了資金，為公司在未來幾年內實現幾個重要的里程碑提供資金，安德魯將在稍後強調這一點。

Thanks, Grant. I'd like to start by reiterating why developing broader coverage vaccines to treat pneumococcal disease matters. Despite widespread administration of effective vaccines, the global impact of disease remains significant and is associated with high-case fatality rates, antibiotic resistance, and meningitis.

謝謝，格蘭特。首先，我想重申為什麼開發覆蓋範圍更廣的疫苗來治療肺炎球菌疾病很重要。儘管廣泛使用了有效的疫苗，但疾病的全球影響仍然很大，並與高病死率、抗生素抗藥性和腦膜炎有關。

In the US alone, the standard of care pediatric and developed cost of vaccines cover only approximately 30% to 50% of circulating disease. As a result, the public health community continues to affirm the need for broader-spectrum vaccine to prevent IPD. We designed our PCVs to expand coverage and still include all of the serotypes covered by the currently marketed vaccines that were most prevalent when these vaccines were originally developed. The ability to both add newly circulating strains and maintain pressure on previously circulating strains is critical from a global health perspective.

僅在美國，兒科護理標準和疫苗開發成本僅涵蓋約 30% 至 50% 的循環性疾病。因此，公共衛生界繼續確認需要更廣譜的疫苗來預防 IPD。我們設計的 PCV 旨在擴大覆蓋範圍，並且仍然包括目前市售疫苗所涵蓋的所有血清型，這些血清型在這些疫苗最初開發時最為流行。從全球健康的角度來看，添加新的循環菌株並保持對先前循環菌株的壓力的能力至關重要。

Based on the totality results from the 24 adult Phase 2 program that Grant referred to earlier, we believe we have the opportunity to set a new bar for pneumococcal vaccines by delivering broader coverage and higher immune responses relative to conventional PCVs. Following the completion of the Phase 2 adult program, we had a successful end of Phase 2 meeting with the FDA focused on the VAX-24 adult Phase 3 clinical program.

根據格蘭特之前提到的 24 個成人第二階段計劃的總體結果，我們相信我們有機會透過提供相對於傳統 PCV 更廣泛的覆蓋範圍和更高的免疫反應來為肺炎球菌疫苗設定新的標準。在 2 期成人計畫完成後，我們與 FDA 成功結束了 2 期會議，重點討論了 VAX-24 成人 3 期臨床計畫。

We believe there is agreement with the FDA on the clinical design of this program, including the approximate overall number of subjects, the primary and secondary endpoints for the pivotal non-inferiority study as well as confirmation that the planned immunogenicity analyses are sufficient to support licensure and an efficacy study is therefore not required. Regardless of whether we advance VAX-24 or VAX-31, we expect either Phase 3 program to include up to five studies to support licensure and the broad label.

我們相信 FDA 已就該計畫的臨床設計達成一致，包括受試者的大致總數、關鍵非劣效性研究的主要和次要終點，以及確認計劃的免疫原性分析足以支持許可因此不需要進行功效研究。無論我們推進 VAX-24 還是 VAX-31，我們預計第 3 階段計劃將包括最多五項研究以支援許可和廣泛標籤。

Additionally, as part of the ongoing CMC-focused discussions, we received encouraging input from the FDA regarding the VAX-24 adult licensure requirements. We are afforded this dialogue under the VAX-24 Adult Breakthrough Therapy Designation expect to seek additional CMC-focused input from the FDA as we continue to prepare for an adult Phase 3 program for either VAX-24 or VAX-31 and future BLA submissions.

此外，作為正在進行的以 CMC 為重點的討論的一部分，我們收到了 FDA 關於 VAX-24 成人許可要求的令人鼓舞的意見。我們在VAX-24 成人突破性療法指定下進行了這次對話，希望在我們繼續為VAX-24 或VAX-31 以及未來BLA 提交的成人3 期計劃做準備時，尋求FDA 額外的以CMC 為重點的投入。

For VAX-31, we are thrilled to see that our Phase 3 adult study progressed from IND accessions to enrollment completion in approximately three months. In total, the study enrolled 1,015 adults aged 50 and older and is evaluating safety, tolerability, and immunogenicity at three doses, low, middle, and high, compared to Prevnar 20, which I will refer to PCV20. Similar to the criteria for the VAX-24 [ bill ] Phase 2 program, the VAX-31 study will compare the opsonophagocytic activity or OPA and IgG responses compared to PCV20 for the 20 serotypes in common. And for the 11 serotypes, you need to VAX-31, the study is evaluating the percentage subject to achieve a four-fold rise in OPA titers, which is the established precedent and a basis for approval.

對於 VAX-31，我們很高興看到我們的 3 期成人研究在大約三個月內從 IND 加入進展到註冊完成。該研究總共招募了 1,015 名 50 歲及以上的成年人，正在評估低、中、高三種劑量與 Prevnar 20（我稱之為 PCV20）相比的安全性、耐受性和免疫原性。與 VAX-24 [法案] 2 期計畫的標準類似，VAX-31 研究將比較 20 種常見血清型的調理吞噬活性或 OPA 和 IgG 反應與 PCV20 的反應。而對於11种血清型，則需要VAX-31，該研究正在評估實現OPA滴度上升四倍的受試者百分比，這是既定的先例，也是批准的基礎。

Based on our preclinical data for VAX-31 and the clinical data for VAX-24, particularly the mixed-dose arm for both adult Phase 2 studies, we are optimistic about the prospects for the VAX-31 data. Recall that in the mixed-dose arm from the VAX-24 study, we simulated the amount of carrier protein that is in the VAX-31 middle dose. We believe those immunogenicity results give us a preview of what we might expect for VAX-31. If we see results for VAX-31 that are comparable to those from the mixed-dose arms of the VAX-24 study, in which all the three serotypes hit the non-inferiority endpoint, we believe that would be a very fine enough.

根據我們對 VAX-31 的臨床前數據和 VAX-24 的臨床數據，特別是兩項成人 2 期研究的混合劑量組數據，我們對 VAX-31 數據的前景持樂觀態度。回想一下，在 VAX-24 研究的混合劑量組中，我們模擬了 VAX-31 中等劑量中載體蛋白的量。我們相信這些免疫原性結果讓我們預覽了 VAX-31 的預期。如果我們看到 VAX-31 的結果與 VAX-24 研究中混合劑量組的結果相當（其中所有三種血清型均達到非劣效性終點），我們相信這已經足夠好了。

Similar to our expectations for VAX-24 Phase 2 adult program for the VAX-31 study upcoming readout, our focus is on the OPA geometric metric mean ratios for each serotype rather than the confidence intervals. Because this Phase 1/2 study will be smaller in size than the Phase 3 study, you can expect these confidence intervals to be wider. It's very possible that several may cross the 0.5 non-inferiority threshold. If the GMRs are 0.6 or higher for each serotype in the study, prior Phase 3 studies have shown that these ratios are adequate to achieve the non-inferiority threshold.

與我們對即將發表的 VAX-31 研究的 VAX-24 第 2 期成人計劃的預期類似，我們的重點是每种血清型的 OPA 幾何指標平均值比率，而不是置信區間。由於此第 1/2 階段研究的規模將小於第 3 階段研究的規模，因此您可以預期這些信賴區間會更寬。很可能有幾個可能超過 0.5 個非劣效閾值。如果研究中每种血清型的 GMR 為 0.6 或更高，則先前的 3 期研究表明這些比率足以達到非劣效性閾值。

When considering the historical presence for a broader-spectrum PCV candidates, our focus has been on the important societal benefits of expanding disease protection. With this public health goal in mind, for all prior PCV programs that have been approved, regulatory authorities have accepted generally lower overall immune responses and some missed non-inferiority endpoints versus the standard of care. We believe, however, based on our VAX-24 data, that our carrier-sparing platform has the potential to change this historical pattern by both extending coverage and maintaining immune responses.

在考慮歷史上存在的更廣譜 PCV 候選藥物時，我們的重點是擴大疾病保護所帶來的重要社會效益。考慮到這一公共衛生目標，對於所有先前已批准的 PCV 項目，監管機構已經接受了整體免疫反應普遍較低以及一些與護理標準相比錯過的非劣效性終點。然而，我們相信，根據我們的 VAX-24 數據，我們的載體保護平台有可能透過擴大覆蓋範圍和維持免疫反應來改變這一歷史模式。

With VAX-31, we expect to increase disease coverage by 45% importance over the standard of care in adults today, which is significantly greater than the increase in coverage presented by prior programs.

借助 VAX-31，我們預期疾病覆蓋率將比當今成人護理標準提高 45%，這明顯高於先前計畫的覆蓋率增幅。

We believe this level of improvement will be strongly considered by regulators in their assessment of the potential public health benefits VAX-31 may provide. As our adult programs continue to advance, they are also pleased with the progress we have made with the VAX-24 program [nuke]. VAX-24 has the potential best-in-class profile in this population, and we are excited to be nearing enrollment completion for our infant Phase 2 study.

我們相信，監管機構在評估 VAX-31 可能提供的潛在公共衛生益處時將大力考慮這種改進程度。隨著我們成人專案的不斷推進，他們也對我們在 VAX-24 專案上的進展感到滿意[核子武器]. VAX-24 在這一人群中具有潛在的同類最佳特徵，我們很高興我們的嬰兒 2 期研究即將完成註冊。

Given the size and global nature of the infant market, we are particularly excited about the primary and boosted data readouts expected in 2025. We believe these milestones, along with the VAX-31 adult data readout expected in the third quarter of this year, will further define the full potential and magnitude of the PCV opportunity for Vaxcyte. We look forward to sharing important updates on the progress of our PCV franchise this year.

考慮到嬰兒市場的規模和全球性質，我們對 2025 年預計的主要數據和增強數據讀數感到特別興奮。我們相信這些里程碑以及預計今年第三季公佈的 VAX-31 成人數據將進一步確定 Vaxcyte PCV 機會的全部潛力和規模。我們期待分享今年 PCV 特許經營進展的重要更新。

And I would now like to turn the call over to Andrew.

我現在想把電話轉給安德魯。

Great. Thanks, Jim. On the financials with respect to the income statements, the details of our fourth-quarter and full year 2023 results and the reasons for the variances to the comparable 2022 periods are reflected in our 10-K filing and summarized in our press release. The year-over-year increase in R&D expenses is driven primarily by higher manufacturing expenses related to the planned adult Phase 3 clinical trials and potential future commercial launches of our PCV programs.

偉大的。謝謝，吉姆。在與損益表相關的財務數據方面，我們第四季度和2023 年全年業績的詳細資訊以及與2022 年可比期間出現差異的原因均反映在我們的10-K 文件中，並在我們的新聞稿中進行了總結。研發費用的同比增長主要是由於與計劃的成人 3 期臨床試驗以及我們的 PCV 項目未來潛在的商業推出相關的製造費用增加。

Both R&D and G&A expenses also grew as we invested in our team to support our recent and anticipated growth. The acquired manufacturing life expense of $75 million for the fourth quarter and full year 2023 was related to the exercise of the option with Sutro Biopharma, of which $50 million was paid in cash in the fourth quarter. The 2022 expense for the same item was related to the upfront consideration incurred in connection with the original option agreement entered into with Sutro. I would also note the contribution of the interest income line as a function of our higher cash and investment balances and the higher interest rate environment.

隨著我們對團隊進行投資以支持我們近期和預期的成長，研發和一般行政費用也有所增長。2023 年第四季和全年收購的製造壽命費用為 7,500 萬美元，與 Sutro Biopharma 行使選擇權有關，其中 5,000 萬美元在第四季度以現金支付。同一專案的 2022 年費用與與 Sutro 簽訂的原始選擇權協議相關的預付費用有關。我還要指出利息收入線的貢獻是我們較高的現金和投資餘額以及較高的利率環境的函數。

As we look forward, we expect an increase in 2024 R&D and G&A operating expenses over both full year and Q4 2023 annualized loans, particularly within R&D. This expected increase is primarily a function of our investment to make the required clinical trial materials for a potential VAX-24 or VAX-31 Phase 3 adult program, which will consist of multiple trials, and to continue manufacturing activities to support the potential launches of out PCV programs. While we expect substantial annual growth of our R&D expenses, we do expect the amount to vary by quarter depending on timing of manufacturing activity.

展望未來，我們預計 2024 年研發和一般行政費用營運支出將比全年和 2023 年第四季的年化貸款增加，特別是在研發領域。這一預期增長主要是由於我們投資為潛在的 VAX-24 或 VAX-31 3 期成人計劃（該計劃將包括多項試驗）製造所需的臨床試驗材料，並繼續進行製造活動以支持潛在的上市出PCV 程序。雖然我們預計研發費用將每年大幅成長，但我們確實預計該金額會根據製造活動的時間而按季度變化。

For G&A, we expect the expense growth to be generally steady by quarter. At this time, we do not anticipate any future acquired manufacturing rights expenses.

對於一般管理費用，我們預計每季的費用成長將整體穩定。目前，我們預計未來不會產生任何獲得製造權的費用。

Separate from income statements, in the fourth quarter of last year, we commenced construction and buildout of a dedicated manufacturing suite at Lonza to support the potential global commercialization of our PCV program in connection with the agreement we entered into with them in October. We expect this buildout to take approximately 2 to 2.5 years at a capital cost over this period of approximately $300 million to $350 million. As of year-end 2023, we had incurred $86.5 million of capital and facility buildout expenditures that were reflected on our balance sheet in two separate line items, properties equipment and other assets. A detailed breakdown can be found in our 10-K filed today.

除了損益表之外，去年第四季度，我們開始在 Lonza 建造和擴建專用製造套件，以支持我們 10 月與他們簽訂的協議中 PCV 項目潛在的全球商業化。我們預計這項擴建將需要大約 2 至 2.5 年的時間，在此期間的資本成本約為 3 億至 3.5 億美元。截至 2023 年底，我們發生了 8,650 萬美元的資本和設施建設支出，這些支出反映在我們的資產負債表上兩個單獨的項目：物業設備和其他資產。詳細的細分可以在我們今天提交的 10-K 中找到。

For the remaining construction and buildout cost of this dedicated manufacturing suite, we expect the majority will be incurred in 2024 and the balance in 2025 and perhaps into early 2026. Most of the associated costs will be reflected on our balance sheet in the same two line items I mentioned earlier and will not run through the income statement since the buildup of the suite that's complete and manufacturing activities commenced. There will be a separate and smaller operating expense component over the buildout period that will be reflected during the R&D expenses.

對於該專用製造套件的剩餘建設和擴建成本，我們預計大部分將在 2024 年產生，餘額將在 2025 年甚至 2026 年初產生。大部分相關成本將反映在我們的資產負債表上我之前提到的兩個相同的行項目中，並且自從套件完成和製造活動開始以來不會貫穿損益表。在擴建期間將有一個單獨的、較小的營運費用部分，該部分將反映在研發費用中。

Turning to the balance sheet and cash runway, as Grant noted, we continue to maintain a strong financial position ending in 2023 with $1.24 billion in cash, cash equivalents and investments. This excludes the $816.5 million in net proceeds from the follow-on operating we completed earlier this month.

談到資產負債表和現金跑道，正如格蘭特所指出的那樣，截至 2023 年，我們繼續保持強勁的財務狀況，擁有 12.4 億美元的現金、現金等價物和投資。這還不包括我們本月稍早完成的後續營運帶來的 8.165 億美元淨收益。

Going forward, we expect that our balance sheet will be sufficient to fund our operating expenses and capital expenditure requirements through a number of important milestones over the next few years, including the VAX-31-adult Phase 1/2 study topline data expected in the third quarter of this year, the VAX-24 for infant Phase 2 study primary series and booster dose readout expected by the end of the first quarter and year-end 2025, respectively. The initiation and the anticipated Phase 3 studies for the adult PCV program we elect to advance, which if VAX-24 would include the non-inferiority study in the second half of this year and the remaining study in 2025 and 2026, or VAX-31, the full complement of studies in 2025 and in 2026.

展望未來，我們預計我們的資產負債表將足以透過未來幾年的一些重要里程碑來滿足我們的營運費用和資本支出需求，包括預計在今年第三季度，用於嬰兒的VAX-24 2 期研究的初級系列和加強劑量預計分別於2025 年第一季末和年底公佈。我們選擇推進成人 PCV 計畫的啟動和預期的 3 期研究，如果 VAX-24 將包括今年下半年的非劣效性研究以及 2025 年和 2026 年的剩餘研究，或者 VAX-31 ，2025 年和2026 年研究的全部補充。

The expected topline data from the Phase 3 pivotal non-inferiority study, whether we advance VAX-24 or VAX-31 and the expected completion of the buildout of the dedicated manufacturing suite to support the long-term commercialization of our PCV programs.

第三階段關鍵非劣效性研究的預期頂線數據，無論我們是推進 VAX-24 還是 VAX-31，以及預計完成專用製造套件的建設以支持我們 PCV 項目的長期商業化。

I will now turn it over to Grant for closing remarks.

現在我將把它交給格蘭特做總結發言。

Thanks, Andrew. Before moving to Q&A, I would like to now to the entire team at Vaxcyte and our partners. 2023 was an extraordinary year of validation for VAX-24 and our pipeline. Over the next year, we look forward to several upcoming catalysts that will further define the profiles of our PCV franchise, and I am confident in our ability to execute and further scale our business in 2024 and beyond. We look forward to sharing further updates as the year progresses and we appreciate your interest by joining us today.

謝謝，安德魯。在進行問答之前，我現在想向 Vaxcyte 的整個團隊以及我們的合作夥伴致意。 2023 年是 VAX-24 和我們的管道驗證的非凡一年。明年，我們期待即將出現的幾個催化劑將進一步定義我們 PCV 特許經營權的概況，我對我們在 2024 年及以後執行和進一步擴展業務的能力充滿信心。我們期待隨著時間的推移分享更多的最新消息，並感謝您今天加入我們。

With that, let's take some questions. Operator?

那麼，讓我們提出一些問題。操作員？

(Operator Instructions) Jason Gerberry, Bank of America.

（操作員指示）Jason Gerberry，美國銀行。

I guess, firstly, just as we think about this decision between VAX-31 and 24. You're ultimately measuring yourself against VAX-24. So I'm wondering if you can frame what success looks like. And in the end, would showing a net incremental coverage of three or four strains as measured by statistical NI or good enough point estimates or a fourfold rise collectively across the spectrum. Does that sound like to you what a bar for success looks like?

我想，首先，正如我們思考 VAX-31 和 24 之間的決定。您最終將根據 VAX-24 來衡量自己。所以我想知道你是否可以描述一下成功是什麼樣子的。最後，根據統計 NI 或足夠好的點估計測量，將顯示三到四種菌株的淨增量覆蓋率，或整個譜系總體上升四倍。您覺得這聽起來像是成功的標準嗎？

And then secondly, have you guys explored ways to reduce protein carrier in the 31 valent approach? And the reason I asked is, for some reason, if this iteration of VAX-31 doesn't make the cut off, just wondering if there are ways to potentially go back to the drawing board and to optimize. Thanks.

其次，你們是否探索過在 31 價方法中減少蛋白質載體的方法？我問的原因是，出於某種原因，如果 VAX-31 的這個迭代沒有成功，只是想知道是否有辦法可以回到繪圖板並進行最佳化。謝謝。

As we look forward to that data that we expect to see in the third quarter, we're quite optimistic, the way we're looking at this program is a combination of the empiric evidence generated to date, combined with the circumstances. So from an empirical data perspective, certainly, we have not only, of course, compelling preclinical data with VAX-31, but also the VAX-24 data that's been generated across the Phase 2 program that's readout already with a particular emphasis on that mixed-dose cohort where we were able to already test the cumulative amount of protein carrier that we would expect to have put into the clinic with VAX-31.

當我們期待在第三季度看到的數據時，我們非常樂觀，我們看待這個計劃的方式是結合迄今為止產生的經驗證據和具體情況。因此，從經驗數據的角度來看，當然，我們不僅擁有令人信服的 VAX-31 臨床前數據，而且還擁有跨第 2 階段計劃生成的 VAX-24 數據，這些數據已經讀出，特別強調混合-劑量隊列，我們已經能夠測試我們預計用VAX-31 投入臨床的蛋白質載體的累積量。

So for us, we're really looking, as you point out, and a couple of different end points -- so there's the non-inferiority comparisons to Prevnar 20 across those 20 conjugates and then the Incremental 11 where it's a slightly different endpoint where you're looking at fourfold rise over baseline. So for us, the data that we generated with that VAX-24 cohort demonstrated even at that mixed-dose level, really good comparative results across the 20 that are in Prevnar 20. And then the Incremental 11, set 4 have already readout, the next 7 will come with this study.

因此，對於我們來說，正如您所指出的，我們確實在尋找幾個不同的終點- 因此，在這20 個綴合物上與Prevnar 20 進行非劣效性比較，然後與增量11 進行非劣效性比較，其中它是一個略有不同的終點，其中你看到的是基線的四倍增長。因此，對我們來說，我們用 VAX-24 隊列產生的數據表明，即使在混合劑量水平下，Prevnar 20 中的 20 種藥物也能獲得非常好的比較結果。然後增量 11，第 4 組已經讀出，接下來的 7 個將隨本研究一起出現。

And so, yeah, for us, I think we're feeling good. The data is going to be here in the not-too-distant future. And as you mentioned, the idea of adjusting the ratio, that is certainly something that has been at our disposal historically. We do have a level of precision with our chemistry that permits us to adjust the ratio of sugar to protein in ways that we don't believe anyone else can. We've used that to great effect to date with greater sugar than protein than convention, a la the carrier-sparing conjugates. But for the foreseeable future, we don't think we need to go back to the drawing board on that, but that would be something we could always look at down the road. For us, we've been able to show that adjustments in dose yield improved immune responses.

所以，是的，對我們來說，我認為我們感覺很好。這些數據將在不久的將來出現。正如你所提到的，調整比率的想法，這當然是我們歷史上一直可以使用的東西。我們的化學確實具有一定程度的精確性，使我們能夠以我們認為其他人無法做到的方式調整糖與蛋白質的比例。到目前為止，我們已經使用了比傳統方法更多的糖比蛋白質，以及節省載體的綴合物，取得了巨大的效果。但在可預見的未來，我們認為我們不需要回到繪圖板，但這將是我們在未來可以一直關注的事情。對我們來說，我們已經能夠證明劑量調整可以改善免疫反應。

So the first order, if necessary, would be more likely to come in the form of adjusted doses. But again, as you know, Jason, this is not perfection that's required. The whole focus of this class has been to preserve coverage over historically circulating strains while looking to expand coverage to newly circulating strains. And in that trade, it's been recognized that even with lower immune responses, that's an okay trade-off. Fortunately for us, at least for VAX-24, we didn't look like that was going to be required to push coverage. We'll see what the VAX-31 data looks like. But I guess the point is perfection's not the requirement. We've seen a few missed strains being considered a good tradeoff at least in the eyes of the regulators. And I think ultimately, that's been a good decision, and we'll see what data comes out of this study in the third quarter.

因此，如果有必要，第一個訂單更有可能以調整劑量的形式出現。但同樣，正如你所知，傑森，這並不需要完美。此類的全部重點是保留對歷史流行菌株的覆蓋範圍，同時尋求擴大對新流行菌株的覆蓋範圍。在這項交易中，人們認識到，即使免疫反應較低，這也是一個不錯的權衡。對我們來說幸運的是，至少對於 VAX-24 來說，我們看起來不需要這樣做來擴大覆蓋範圍。我們將看看 VAX-31 數據是什麼樣的。但我想重點是完美不是要求。我們已經看到一些被遺漏的菌株被認為是一個很好的權衡，至少在監管機構看來是如此。我認為最終，這是一個很好的決定，我們將在第三季看到這項研究的數據。

Great. Thank so much.

偉大的。非常感謝。

Roger Song, Jefferies.

羅傑·宋，杰弗里斯。

Great. Congrats for the progress. A few questions from us. Yeah, limited to two. So the first one is with this 31 data in 3Q, you probably need another end of phase meeting with the FDA. The question is how much you can leverage from your 24 end of phase meeting package for that meeting because your timeline is basically going to start a Phase 3 in 2025 and 2024, 2026 if you move forward with 31, particularly around the CMC because that's something seems is holding you back for the 24 at this moment. Thank you.

偉大的。祝賀取得的進展。我們提出幾個問題。是的，僅限兩個。因此，第一個是第三季的 31 個數據，您可能需要與 FDA 舉行另一次階段末會議。問題是你可以從你的24 個階段結束會議包中利用多少，因為你的時間表基本上將在2025 年、2024 年、2026 年開始第3 階段，如果你向前邁進31 個階段，特別是在CMC 周圍，因為這是一些事情此刻似乎讓你在 24 小時前停滯不前。謝謝。

Thanks, Roger. This is Jim Wassil, and I'll try and answer that question for you. I think you're very perceptive in your question. We're hoping to leverage a lot of the study designs that we proposed to put forward with our end of Phase 2 design for VAX-24 and use the very similar design for VAX-31.

謝謝，羅傑。我是吉姆·瓦西爾，我將盡力為您回答這個問題。我認為你的問題很有洞察力。我們希望利用我們在 VAX-24 第二階段設計結束時提出的大量研究設計，並為 VAX-31 使用非常相似的設計。

Obviously, we'll look at the data from the Phase 1/2 of VAX-31. we'll do a reanalysis from a statistical perspective. We'll power the studies appropriately to ensure that we maximize the probability of success in our non-inferiority study in our other Phase 3 studies. But essentially, the proposal that we put forward in VAX-24 will be very similar in terms of the overall study design that we've seen from 31.

顯然，我們將查看 VAX-31 1/2 階段的資料。我們將從統計角度進行重新分析。我們將適當地加強研究，以確保我們在其他 3 期研究中最大限度地提高非劣效性研究的成功機率。但本質上，我們在 VAX-24 中提出的提案在整體研究設計方面與我們在 31 中看到的提案非常相似。

Got it. And how about the CMC portion of the 31?

知道了。31 的 CMC 部分怎麼樣？

Yes. Same thing as well. We're using very similar manufacturing processes. It's not exact manufacturing processes in some cases between the 24 polysaccharides and 31 as well as the drug substance. And of course, the carrier protein is still the same carrier protein. So a lot of similarities between 24 and 31. So whatever we've learned from feedback from the FDA from a CMC perspective from 24, we believe is applicable to 31 as well.

是的。同樣的事情也是如此。我們使用非常相似的製造流程。在某些情況下，24 種多醣體和 31 種多醣體以及原料藥之間的製造流程並不完全相同。當然，載體蛋白仍然是相同的載體蛋白。所以24和31之間有很多相似之處。因此，無論我們從 CMC 角度從 24 的 FDA 回饋中了解到什麼，我們相信也適用於 31。

Excellent. Maybe just a follow-up question. For the 31 higher dose, you mentioned on the call, the mix dose from the [third] 24 making the middle dose for 31. Maybe just any color you can provide related to the high dose for 31, particularly in terms of the carrier protein, how much higher and what are the key serotypes potentially can be dosed higher? If you can give us some color around that. Thank you.

出色的。也許只是一個後續問題。對於 31 較高的劑量，您在電話中提到，[第三] 24 的混合劑量使 31 的中間劑量。也許您可以提供與 31 高劑量相關的任何顏色，特別是在載體蛋白方面，高多少以及哪些關鍵血清型可能可以更高劑量？如果你能給我們一些顏色。謝謝。

Roger, Grant again. Yes, we've spent a little bit more [coy] with regard to the doses we didn't provide more details here just for competitive purposes but we want to make sure that we come out of this Phase 2 experiment with a clear dose to advance to Phase 3. So ergo, the bracketing with lower and higher doses. We haven't gotten into explicit detail, but there's a pretty tight window of dosing that's been historically applied in the pneumococcal [conjugate] vaccine space. So we wouldn't do anything that would be radical there, but we're not going to go into the explicit details of what those are, at least for the time being, and that will be decided at the time we review the data.

羅傑，又是格蘭特。是的，我們在劑量方面花了更多的錢[害羞]，我們在這裡沒有提供更多細節只是為了競爭目的，但我們希望確保我們在第二階段實驗中得出明確的劑量進入第3階段。因此，較低和較高劑量的包圍。我們還沒有詳細說明，但歷史上肺炎球菌[結合]疫苗領域應用的劑量窗口非常嚴格。因此，我們不會在那裡做任何激進的事情，但我們不會詳細討論這些細節，至少暫時不會，這將在我們審查數據時決定。

Understood. Thank you. Thank you for taking the question.

明白了。謝謝。感謝您提出問題。

Salim Syed, Mizuho.

薩利姆賽義德，瑞穗。

This is Erik Lavington on for Salim. I'm curious what your take on possible outcomes for discussions for V116 at the upcoming ACIP meeting might read through to either your decision between VAX-24 and VAX-31 and what it might mean for the comparison in Phase 3?

我是薩利姆的埃里克·拉文頓。我很好奇您對即將召開的 ACIP 會議上 V116 討論的可能結果的看法可能會影響到您對 VAX-24 和 VAX-31 的決定，以及這對第 3 階段的比較可能意味著什麼？

Thanks, Erik, Jim Wassil. So I'll answer this by saying I think many of us know at February 29, ACIP Merck's V116 will be on the agenda I think at that meeting we'll get a better idea of the current thinking of the ACIP pneumococcal working group The pneumococcal working group will most likely present epidemiological data health economic data V116 clinical data, and then they'll make a proposal to the ACIP regarding how to recommend V116, assuming they get FDA approval. So I don't think I'd want to speculate on this, especially since we've going to have a much better idea by the end of this week, what the ACIP position will be.

謝謝艾瑞克、吉姆·瓦西爾。所以我會回答這個問題，我想我們很多人都知道2 月29 日，ACIP Merck 的V116 將被列入議程，我認為在那次會議上我們將更好地了解ACIP 肺炎球菌工作組當前的想法肺炎鏈球菌工作小組很可能會提供流行病學數據、健康經濟數據、V116臨床數據，然後他們將向ACIP提出如何推薦V116的提案，假設他們獲得FDA批准。因此，我認為我不想對此進行猜測，特別是因為我們將在本週末之前對 ACIP 的立場有一個更好的了解。

I will say that I want to highlight V116 is only applicable in the adult population, and it takes a different approach than our PCV program in order for them to reach 21 strains due to the limitations of their technology. They had to remove 9 strains that have been traditionally included in approved PCVs. So with VAX-31, we do have a potential to further increase coverage to approximately 95% of the nation's disease and we're doing this by adding additional strains and maintaining coverage previously circulating strains.

我想說的是，我想強調的是，V116 僅適用於成年人群，由於其技術的限制，它採用了與我們的 PCV 計劃不同的方法，以便使他們達到 21 株。他們必須刪除傳統上已批准的 PCV 中包含的 9 種菌株。因此，借助 VAX-31，我們確實有潛力進一步將覆蓋範圍擴大到全國約 95% 的疾病，我們正在透過添加額外菌株並維持先前流行菌株的覆蓋範圍來實現這一目標。

We'll wait and see. We'll see what the outcomes are. I think 24 will have a strong position regardless. Obviously, 31, which contains, for the most part, all the strengths in both vaccines, we'll be in a strong position to increase coverage and really take a strong position if it gets approved.

我們拭目以待。我們將看看結果如何。我認為無論如何，24都會佔據強勢地位。顯然，31 在很大程度上包含了兩種疫苗的所有優點，如果它獲得批准，我們將處於擴大覆蓋範圍的有利地位，並真正佔據有利地位。

Got it. Thank you.

知道了。謝謝。

Dave Risinger, Leerink Partners.

戴夫‧瑞辛格 (Dave Risinger)，Leerink 合夥人。

So first, I wanted to say congrats on the corporate progress and appreciate the updates. I guess I have two questions for Grant and Jim. First, ACIP-preferred recommendations are rare, but Vaxcyte could be particularly well positioned for a potential preferential recommendation for VAX-31. Could you just comment on that notion and provide your perspective? And then second, could you elaborate more, Jim, on your comment about potential prime boost opportunity in adults? Thanks very much.

首先，我想說祝賀公司的進展並感謝更新。我想我有兩個問題想問格蘭特和吉姆。首先，ACIP 優先推薦的情況很少見，但 Vaxcyte 可能特別適合成為 VAX-31 的潛在優先推薦。您能否評論一下這個概念並提供您的觀點？其次，吉姆，您能否詳細說明您對成人潛在的優質提昇機會的評論？非常感謝。

Yeah. Thanks for that, Dave. I appreciate the acknowledgment. And Jim is our ACIP guru, so let me hand you to Jim let's see if he can respond to that question.

是的。謝謝你，戴夫。我很感謝您的認可。吉姆是我們的 ACIP 大師，所以讓我把你交給吉姆，讓我們看看他是否能回答這個問題。

Yeah so.

所以啊。

Let me jump in. So yes certainly, the ACIP has within its purview the right to extend a preferred recommendation. They have been limited in those decisions in the past. The most recent course was with Shingrix, over Zostavax for the shingles vaccines. It's been more limited in the pneumococcal conjugate vaccine space, but it does occur. And we even see that with Prevnar 20 in certain circumstances.

讓我跳進去。所以，當然，ACIP 在其職權範圍內有權提出首選建議。過去他們的這些決定受到了限制。最近的課程是使用 Shingrix，而不是 Zostavax 用於帶狀皰疹疫苗。這種情況在肺炎鏈球菌結合疫苗領域受到更多限制，但它確實發生了。在某些情況下，我們甚至在 Prevnar 20 上看到了這一點。

So there are a lot of pundits out there, Dave, speculating on how the ACIP is going to react. And the margin of improvement does need to be quite material from an efficacy perspective or coverage perspective. But when you have an opportunity to potentially extend the coverage with a singular vaccine to as high as 95%, while continuing to maintain pressure on previously circulating strains, to us, objectively, we think that is the profile that would warrant a preferred recommendation.

戴夫，有很多專家在猜測 ACIP 會如何反應。從功效角度或覆蓋範圍角度來看，改進幅度確實需要相當大。但是，當您有機會將單一疫苗的覆蓋率擴大到高達 95%，同時繼續對以前流行的菌株保持壓力時，對我們來說，客觀地，我們認為這是值得優先推薦的情況。

So we'll have our day if things stay on track. we'll see how they react to the V116 profile. But certainly, from our perspective, we believe there is that possibility for us, but V116 will be another data point.

因此，如果一切順利的話，我們就會迎來美好的一天。我們將看看他們對 V116 設定檔有何反應。但當然，從我們的角度來看，我們相信我們有這種可能性，但 V116 將是另一個數據點。

I think what we had heard was there was hope at Merck that there was going to be an opportunity for preferred recommendation. We'll find out, I think that's being walked back a bit from what we're reading. But as Jim pointed out, before the week is out we'll have a leading indicator.

我認為我們聽到的是默克公司希望有機會獲得優先推薦。我們會發現的，我認為這與我們正在閱讀的內容有所不同。但正如吉姆指出的那樣，在本週結束之前，我們將有一個領先指標。

In terms of your question on prime boost in previous discussions of the ACIP, both the 15-day end and 20 got approved. There was a debate over whether we should start immunizing starting at 50 years of agents and the current recommendation of 65. I think there's a lot of support to that. And the reason is the data says that almost the third -- probably around 28% to 30% of adults right now are in an at-risk category or a high-risk category for getting pneumococcal disease, particularly pneumococcal pneumonia.

至於你在ACIP之前討論中關於prime boost的問題，15天結束和20天結束都得到了批准。關於我們是否應該從使用 50 年的疫苗開始免疫存在爭議，目前的建議是 65 年。我認為這得到了很多人的支持。原因是數據顯示，目前約有 28% 至 30% 的成年人屬於感染肺炎球菌疾病的高風險族群或高風險族群，尤其是肺炎鏈球菌肺炎。

And these are groups that it's not just asplenics and malignancies and HIV and severe immunosuppression. These are a lot more common groups. You have severe asthma, COPD, you have diabetes, chronic lung, chronic liver disease. And the belief is that, that population in terms of percentage in that age group is only going to grow. And historically, at-risk recommendations haven't really gotten penetration. So there's been some debate about moving the recognition on 50. And then that would mean most likely that you would need to get a booster at 65%, so there could be a prime of 50 and a boost at 65. And we'll also see some of that debate, I think, coming up in the upcoming (inaudible).

這些群體不僅僅是脾臟、惡性腫瘤、愛滋病毒和嚴重的免疫抑制。這些是更常見的群體。你患有嚴重氣喘、慢性阻塞性肺病、糖尿病、慢性肺病、慢性肝病。人們相信，該年齡層的人口比例只會增加。從歷史上看，有風險的建議並沒有真正普及。因此，關於將認可度移至 50 存在一些爭論。那麼這很可能意味著您需要在 65% 時獲得助推器，因此可能會有 50 的質數和 65 的助推器。我認為，我們也會在即將到來的會議中看到一些爭論（聽不清楚）。

That's great. And just to follow up, if I may. Could you talk about your Phase 3 plans in adults and your age strategy?

那太棒了。如果可以的話，我只是想跟進一下。您能談談您的成人第三階段計劃和年齡策略嗎？

Well, from an FDA licensure perspective, the adult label is usually extended at age 18 and up. So we'll be looking for the same broad label that's been obtained with other pneumococcal conjugate vaccines. So the next look then is at the ACIP as to how they grant the universal recommendation. But from a licensure perspective, we'll be looking to have and across the spectrum indication, but that is a question of usage. And as Jim said, was universally recommended the uptick is much greater than when it's restricted to at-risk population.

嗯，從 FDA 許可的角度來看，成人標籤通常會延長到 18 歲及以上。因此，我們將尋找與其他肺炎鏈球菌結合疫苗相同的廣泛標籤。因此，接下來要關注的是 ACIP 他們如何授予普遍建議。但從許可的角度來看，我們將尋求跨頻譜的指示，但這是一個使用問題。正如吉姆所說，人們普遍認為，上升幅度比僅限於高危險群時要大得多。

And I'd only add that given the interest in these at-risk groups in 50- to 65-year-olds, we'll make sure they have adequate enrolled at-risk groups in our clinical study so that we can support [if the ACIP] does want to move down to 50 years of age on clinical data to help with the decision.

我只想補充一點，鑑於對 50 至 65 歲高風險人群的興趣，我們將確保他們在我們的臨床研究中納入足夠的高風險人群，以便我們可以支持 [如果ACIP] 確實希望根據臨床數據將年齡下移至50 歲，以協助做出決定。

That's super helpful. Thanks so much.

這非常有幫助。非常感謝。

Umer Raffat, Evercore.

烏默·拉法特，Evercore。

Among the new serotypes you're adding to VAX-31, there's one in particular, which has a bunch of literature on it's suggesting it's very unique and perhaps difficult to manufacture. I'm referring to 35B. Can you speak to your confidence in the manufacturing as well as early immunogenicity that you saw in preclinical models of 35B in particular. Secondly, is it your expectation that Pfizer's broader spectrum program, 24, 25 valent is using a second carrier protein beyond CRM197? Thank you.

在您添加到 VAX-31 的新血清型中，有一個特別重要，有大量文獻表明它非常獨特，而且可能難以製造。我指的是35B。您能否談談您對製造以及您在 35B 臨床前模型中看到的早期免疫原性的信心？其次，您是否期望輝瑞的更廣譜計劃（24、25 價）使用 CRM197 以外的第二種載體蛋白？謝謝。

Yeah. Maybe I'll answer the second one first, and then Jim will address the 35B question, (inaudible). Thank you for both of those. As it relates to the fourth-generation program, yes, Umer, it's hard to know exactly what they're doing. So from what they've been willing to disclose, they've been considering all number of potential changes to try to extend beyond a 20 valent vaccine.

是的。也許我會先回答第二個問題，然後吉姆會回答 35B 問題，（聽不清楚）。謝謝你們這兩點。由於它與第四代計劃有關，是的，烏默，很難確切地知道他們在做什麼。因此，從他們願意透露的情況來看，他們一直在考慮各種潛在的改變，以嘗試超越 20 價疫苗。

But at the most recent earnings results, they seem to indicate that whatever incremental strains would be layered on top of what would presumably be the 20 streams that are in Prevnar 20. And there, it then comes down to, is it a unique protein carrier? Is it different chemistries? Is it different linkers or some sort of other formulation?

但從最近的獲利結果來看，他們似乎表明，無論增加什麼壓力，都將疊加在 Prevnar 20 中可能的 20 個流之上。那麼，歸根結底，它是一種獨特的蛋白質載體嗎？是化學成分不同嗎？是不同的接頭還是某種其他配方？

But it's hard to know beyond that. I don't think they've gotten detailed with regard to that. That said, this idea of the notion of using an additional protein carrier that something other sponsors have tried going back to GSK's first foray in pneumococcal conjugate vaccines. And then more recently, with Sanofi's approach intermingling diphtheria toxin and tetanus toxoid. And those have turned out to be a bit problematic as Sanofi has not decided to proceed in the adult indication.

但除此之外就很難知道了。我認為他們還沒有對此進行詳細說明。也就是說，使用額外的蛋白質載體的想法是其他贊助商嘗試過的，可以追溯到葛蘭素史克首次涉足肺炎球菌結合疫苗。最近，賽諾菲的方法將白喉毒素和破傷風類毒素混合在一起。事實證明這些有點問題，因為賽諾菲尚未決定繼續進行成人適應症。

So it's unclear at the moment, but other attempts in a similar vein haven't worked out particularly well. But we couldn't say for sure if that's the approach they're trying as of yet. And as to 35B, Jim, do you want to comment?

所以目前還不清楚，但其他類似的嘗試並沒有特別好的效果。但我們還不能確定這是否是他們目前正在嘗試的方法。至於 35B，吉姆，你想發表評論嗎？

Traditionally, we limited our comments on some of this due to proprietary issues. But I'll say 35B is an important serotype is one of the more common circulating streams in adults, and it's probably the most significant contributor to otitis media in the US today. So we are very keen on making sure that it is manufactured appropriately and that it works well in VAX-31.

傳統上，由於專有問題，我們對其中一些內容的評論受到限制。但我要說的是，35B 是一種重要的血清型，是成人中更常見的循環流之一，它可能是當今美國中耳炎最重要的因素。因此，我們非常熱衷於確保其製造得當並且在 VAX-31 中運作良好。

Thank you.

謝謝。

Seamus Fernandez, Guggenheim.

謝默斯·費爾南德斯，古根漢。

So I wanted to just talk a little bit about pediatric and how you'd like to set expectations for the three-dose data? I know that that is something that Merck has pitched as part of the [vaccine advance] story, so it is interesting to know I know that breadth is likely to dominate but three-dose regimen has been quite successful overseas. Just interested to just know how you guys are thinking about the opportunity for actually perhaps a superior profile at your third dose versus the Prevnar 20 third dose, just because a number of those serotypes appear to miss at three doses and then really required the fourth dose to catch up. So just interested to know how you're thinking about that and its importance from a market perspective longer term?

所以我想談談兒科，以及您希望如何設定三劑數據的預期？我知道這是默克公司在[疫苗進展]故事中所宣傳的內容，所以有趣的是，我知道廣度可能占主導地位，但三劑療法在海外已經相當成功。只是想知道你們如何看待第三劑與 Prevnar 20 第三劑相比實際上可能具有更好的特徵的機會，只是因為其中許多血清型在三劑時似乎錯過了，然後確實需要第四劑趕上。那麼只是想知道您如何看待這一點及其從長期市場角度來看的重要性？

And then just the second question is on whether you choose 24, 31 in the adult vaccination program, are you confident that you won't be required to study versus V116? Or is that something that could be decided after the ACIP recommendation in June? Thanks.

那麼第二個問題是，您在成人疫苗接種計劃中是否選擇24、31，您是否有信心不會被要求學習V116？或者這是否可以在 6 月 ACIP 建議後做出決定？謝謝。

Yes. Thanks for the question, Seamus. So yes, as it relates to the infant indication, obviously, a critical part of the market, three quarters of the sales consistently in that space. And as you referred to three-dose series, I wasn't sure exactly which direction you were until you expounded a bit.

是的。謝謝你的提問，西莫。所以是的，因為它與嬰兒適應症相關，顯然是市場的關鍵部分，四分之三的銷售額始終集中在該領域。當你提到三劑系列時，在你詳細說明之前我不確定你到底是哪個方向。

But yes, to be clear, in US, we have a three-plus-one approach. So three vaccinations within the first six months of life. That's called the primary series. And then the fourth dose comes in the form of a boost the next year.

但是，需要明確的是，在美國，我們有一個三加一的方法。因此，在出生後的前六個月內接種三次疫苗。這就是所謂的初級系列。然後第四劑疫苗會在明年以加強劑的形式出現。

In Europe, they restrict that primary series to only two vaccinations and then the third dose the next year. So it's really a three in Europe versus four-dose approach.

在歐洲，他們將主要係列限制為僅接種兩次疫苗，然後在明年接種第三劑。所以在歐洲這其實是三劑與四劑的方法。

And as you say, less doses create more pressure on lower immune responses. And so when Pfizer studied Prevnar 20 in infants in US and Europe, the impact of the one less dose was quite profound. So in US, there were six of the serotypes that miss the non-inferiority comparison to Prevnar 13 after the primary series. And one can imagine that when you only give two vaccinations with a vaccine that's providing lower immune responses, the impact of that would be felt in a fewer vaccination approach. And sure enough, the results of their Phase 3 study in Europe had 11 of the common serotypes missed the non-inferiority comparison at the primary series.

正如你所說，較少的劑量會對較低的免疫反應產生更大的壓力。因此，當輝瑞在美國和歐洲的嬰兒中研究 Prevnar 20 時，少一劑量的影響是相當深遠的。因此，在美國，有 6 种血清型在初選系列後未能與 Prevnar 13 進行非劣效比較。人們可以想像，當您只用一種免疫反應較低的疫苗接種兩次疫苗時，透過較少的疫苗接種方法就能感受到其影響。果然，他們在歐洲進行的 3 期研究結果顯示，11 種常見血清型錯過了主要係列的非劣效性比較。

So that has been a big question mark. Nonetheless, the CHMP in Europe did recently recommend that Prevnar 20 ought to be approved. So that will be interesting to see how that plays out with that many miss non-inferiority comparisons.

所以一直都是一個很大的問號。儘管如此，歐洲 CHMP 最近確實建議批准 Prevnar 20。因此，看看這如何與許多錯過的非劣效性比較一起發揮作用將會很有趣。

But to your point, what we've seen at least in adults with VAX-24 data is that we are, for the most part, getting higher immune responses relative to Prevnar 20. And if that's the case, it could widen the advantage certainly in a three-dose regimen versus a four-dose regimen.

但就你的觀點而言，我們至少在使用 VAX-24 數據的成年人中看到的是，在很大程度上，相對於 Prevnar 20，我們獲得了更高的免疫反應。如果是這樣的話，那麼與四劑量方案相比，三劑量方案肯定會擴大優勢。

So yeah, we'll have to see how some of this plays out with regard to how the European authorities handle that -- the study that we're running that will read out in 2025 with VAX-24 in infants is the conventional three-plus-one approach. So that's the data we'll start with. But to the extent we see higher immune responses potentially once again after that primary series, that could set us up for a potentially better outcome to create even further competitive advantage relative to Prevnar 20 in Europe, but we'll see what that data looks like next year.

所以，是的，我們必須看看歐洲當局如何處理這一問題——我們正在進行的研究將於 2025 年在嬰兒中使用 VAX-24 進行研究，該研究是傳統的三項研究——加一的方法。這就是我們開始的數據。但就我們在初選系列之後可能再次看到更高的免疫反應而言，這可能會讓我們獲得更好的結果，從而在歐洲相對於Prevnar 20 創造進一步的競爭優勢，但我們將看看數據是什麼樣子的明年。

And then, Seamus, you were also asking about the potential V116 comparisons. I thought you were first talking about VAX-24 versus VAX-31 [in peds], but obviously, you must be talking about adults only given that V116 will be restricted to the adult population to be extended and gets approved. So yeah, I think we're going see -- we're going to benefit to having seen not only how the conversation is progressing with the ACIP later this week, but by the time we would expect to get our VAX-31 data, we'll know for sure if the vaccine is approved. And if so, how it's sequenced or recommended relative to Prevnar 20.

然後，Seamus，您還詢問了潛在的 V116 比較。我以為你首先是在談論 VAX-24 與 VAX-31 [在兒童中]，但顯然，你一定是在談論成年人，因為 V116 將僅限於成年人群才能擴展並獲得批准。所以，是的，我認為我們將會看到——我們不僅會受益於本週晚些時候與 ACIP 的對話進展情況，而且到我們期望獲得 VAX-31 數據時，我們會確切地知道疫苗是否獲得批准。如果是這樣，相對於 Prevnar 20 的排序或推薦方式為何。

So yeah, I think on that information, we'll have a much better sense of what the appropriate comparison would be for either VAX-24 or VAX-31, VAX-31 in particular. So I think that's a bit of a wait and see. Jim, anything to add?

所以，是的，我認為根據這些信息，我們將更好地了解 VAX-24 或 VAX-31（尤其是 VAX-31）的適當比較。所以我認為這還需要觀望。吉姆，有什麼要補充的嗎？

No, I think that's fair. I think that if there's a non-preferential recommendation, then I think it will be up to us to choose which of the competitors we can choose to use in Phase 3.

不，我認為這是公平的。我認為，如果有非優先推薦，那麼我認為我們應該選擇在第三階段使用哪些競爭對手。

Great. Thank you, guys. Appreciate it.

偉大的。感謝你們。欣賞它。

Louise Chen at Cantor Fitzgerald.

坎托·菲茨杰拉德 (Cantor Fitzgerald) 的路易絲·陳 (Louise Chen)。

I wanted to ask you on your global manufacturing capacity and how this gives you a competitive advantage, and then what capacity will you have once you complete this buildup?

我想問一下你們的全球製造能力，這如何為你們帶來競爭優勢，那麼一旦你們完成這個建設，你們將擁有什麼能力？

And second question I wanted to ask you was just on the infants. Are you going to also choose either VAX-24 or VAX-31 for infant? What are you thinking here? And what is your VAX-31 adult data going to give you as you think about the infant opportunity.

我想問你的第二個問題是關於嬰兒的。您是否還要為嬰兒選擇 VAX-24 或 VAX-31？你在想什麼？當您考慮嬰兒機會時，您的 VAX-31 成人數據會為您帶來什麼。

Yeah. Thanks for the questions, Louise. Yeah, so as it relates to the manufacturing buildout, from a competitive perspective, it's really table stakes, if you will. If you can't supply these vaccines at the appropriate capacity, then how can you expect the ACIP amount on others to make a broad recommendation for your vaccine? So for us, it's been fundamental to unlocking the full value of these vaccines is to stay ahead of that capacity so as to have not only the ability to deliver but the profile that would warrant preferred recommendation ideally. And so that's been absolutely crucial to this whole story, and I think we've been able to stay ahead of that.

是的。謝謝你的提問，路易絲。是的，因為它與製造業擴建有關，從競爭的角度來看，如果你願意的話，這確實是賭注。如果你不能以適當的能力供應這些疫苗，那麼你怎麼能指望其他人的 ACIP 數量對你的疫苗做出廣泛的建議呢？因此，對我們來說，釋放這些疫苗的全部價值的根本是保持領先的能力，以便不僅具有交付的能力，而且具有理想的首選推薦的特徵。因此，這對整個故事來說絕對至關重要，我認為我們已經能夠保持領先地位。

We're in a position to launch out of existing Lonza infrastructure, where we've been making these materials just study clinically. And then late last year, as you all know, we made the strategic decision to best in a dedicated facility at Lonza. And as you requested, the way we're thinking about that dedicated facility is one that would be able to satisfy the global demand from the developed world for either VAX-24 or VAX-31 in both of the adult and infant indications. So we really expect that one to really deliver for us to maximize the opportunity that we think is at hand.

我們能夠從現有的 Lonza 基礎設施中推出這些基礎設施，我們一直在其中生產這些材料，僅用於臨床研究。眾所周知，去年年底，我們做出了戰略決策，力爭在龍沙的專用設施中實現最佳營運。如您所要求的，我們考慮建立專用設施的方式是能夠滿足已開發國家對成人和嬰兒適應症的 VAX-24 或 VAX-31 的全球需求。因此，我們確實希望它能夠真正為我們提供最大程度的利用我們認為手頭上的機會。

And then to your question about VAX-24 versus VAX-31 going forward, I think it's really an indication-dependent conversation. So for us, we find ourselves in a position where both VAX-24 and VAX-31 have an opportunity to reach the market on the same timeline. So with the right VAX-31 data later this year, naturally, it would make sense for us to move to deliver the most broadly protective vaccine that we can. And ideally, that would be VAX-31. If not, we know VAX-24 looks really good as well. And so we'll wait to see that data before anointing which one to advance.

然後，關於您關於未來 VAX-24 與 VAX-31 的問題，我認為這實際上是一個依賴適應症的對話。因此，對我們來說，我們發現 VAX-24 和 VAX-31 有機會在同一時間段進入市場。因此，有了今年稍後正確的 VAX-31 數據，我們自然有理由採取行動，盡可能提供最廣泛的保護性疫苗。理想的情況是 VAX-31。如果沒有，我們知道 VAX-24 看起來也很不錯。因此，我們將等待查看該數據，然後再指定要推進哪一項。

That said, in the infant market, we're already well ahead with VAX-24. And so for us, we're contemplating either or both VAX-24 or VAX-31 in the infant indication, just because we know we can bring VAX-24 to market faster based on the path we're on today. So it's a little more nuanced in the infant indication because of that sequencing.

也就是說，在嬰兒市場，我們的 VAX-24 已經遙遙領先。因此，對我們來說，我們正在考慮在嬰兒適應症中使用VAX-24 或VAX-31 之一或兩者，只是因為我們知道根據我們今天的路徑，我們可以更快地將VAX-24 推向市場。因此，由於這種排序，嬰兒適應症的情況更加微妙。

Thank you.

謝謝。

Joseph Stringer, Needham.

約瑟夫‧斯金格，李約瑟。

Just a couple of a quick ones on the pre-clinical programs. You briefly mentioned those. But could you just give us a quick sense b which one you think could end in the clinic first in particular in Strep A, I'm curious if you could give us a quick outline of the competitive landscape there and what you think the commercial opportunity in that indication is.

只是一些關於臨床前項目的快速介紹。您簡單地提到了這些。但是您能否給我們快速介紹一下您認為哪種可能首先在診所結束，特別是鏈球菌 A，我很好奇您能否給我們簡要介紹一下那裡的競爭格局以及您認為的商業機會在那個跡像是。

Sure. Thanks, Joe. So as we stated, we've got three other pipeline projects. We've got a group-based strep periodontitis and a shigella. All three are moving forward in early-stage preclinical development. We haven't guided to when they would go in the clinic for the year. I think the one that I believe is most advanced at this point is the one that you mentioned, which is Group A Strep.

當然。謝謝，喬。正如我們所說，我們還有其他三個管道項目。我們有基於族群的鏈球菌性牙周炎和志賀氏菌。這三者都在早期臨床前開發中取得進展。我們還沒有指導他們今年什麼時候去診所。我認為目前最先進的就是您提到的 A 型鏈球菌。

The Group A Strep vaccine, I think has a very important role. I think it's one of the most underappreciated diseases over 500,000 deaths due to Group A Strep that occur every year due to rheumatic heart disease. But it's a ubiquitous disease-causing pharyngitis, mainly in school entry kids as well as young toddlers. It's not treated aggressively with antibiotics, which means that there's a significant amount of antibiotic prescriptions associated with this disease.

我認為A組鏈球菌疫苗具有非常重要的作用。我認為這是最被低估的疾病之一，每年因風濕性心臟病導致 A 型鏈球菌死亡人數超過 50 萬人。但這是一種普遍存在的致病性咽炎，主要發生在入學兒童和幼兒。它沒有用抗生素積極治療，這意味著有大量的抗生素處方與這種疾病有關。

And also subsequently, you would expect growing levels of antimicrobial resistance have led to increasing importance of finding a vaccine to prevent against this. And there's recent economic studies that say that medical and indirect costs are around $5 billion a year. So a vaccine that can have some degree of efficacy, a reasonable amount of at significantly have direct medical cost offset. So I think you'll see a commercial opportunity here in school entry kids potentially causes.

隨後，您會預期抗菌素抗藥性水平的不斷提高導致尋找疫苗來預防這種情況變得越來越重要。最近的經濟研究表明，每年的醫療和間接成本約為 50 億美元。所以一種疫苗只要能有一定程度的功效，合理的用量在很大程度上可以抵銷直接的醫療成本。因此，我認為您會在入學兒童中看到潛在的商業機會。

And then the one area I haven't mentioned is there's high rates of invasive disease and owner adults as well. So we can see a very similar type of recommendation. In fact, a little bit more because you're immunizing school entry kids as well, that you see with the PCVs. So we're really excited about this program.

我沒有提到的一個領域是，侵襲性疾病和成年主人的發生率很高。所以我們可以看到非常相似的推薦類型。事實上，更多一點是因為您也在為入學兒童進行免疫接種，就像您在 PCV 中看到的那樣。所以我們對這個計劃感到非常興奮。

And I think from a competitive standpoint, Joe, it's not as active as certainly the PCV space is (inaudible).

我認為從競爭的角度來看，喬，它並不像 PCV 領域那麼活躍（聽不清楚）。

Yes. There's minimal, there's a few academic centers and one pharma company there currently looking at the Group A Strep at least so minimal competitive environment as well.

是的。目前，那裡有一些學術中心和一家製藥公司正在研究 A 型鏈球菌，至少競爭環境也很小。

Great. Thank you for taking our question.

偉大的。感謝您提出我們的問題。

Thank you. And ladies and gentlemen, it appears we have no further questions today. So that will conclude today's Vaxcyte fourth-quarter and full year 2023 earnings conference call. Please disconnect your lines at this time, and have a wonderful day.

謝謝。女士們先生們，看來我們今天沒有其他問題了。今天的 Vaxcyte 第四季和 2023 年全年財報電話會議到此結束。請此時斷開線路，祝您有美好的一天。

Thanks for joining, everyone.

感謝大家的加入。