Vaxcyte Inc (PCVX) 2024 Q4 法說會逐字稿

Good afternoon. My name is Jess, 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 2024 financial results conference call. (Operator instructions) Today's call is being recorded. I would now like to turn the call over to Mr. Andrew Guggenhime, President and Chief Financial Officer of Vaxcyte. Please go ahead, sir.

午安.我叫傑西，今天我將擔任你們的會議主持人。現在，我歡迎大家參加 Vaxcyte 第四季和 2024 年全年財務業績電話會議。（接線員指示）今天的通話正在錄音。現在，我想將電話轉給 Vaxcyte 總裁兼財務長 Andrew Guggenhime 先生。先生，請繼續。

Thank you, operator, and good afternoon, everyone. I'd like to welcome you to Vaxcyte's Earnings Conference Call to discuss our 2024 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，討論我們的 2024 年業績並提供業務更新。今天與我一同出席的還有：我們的執行長格蘭特‧皮克林 (Grant Pickering) 和我們的執行副總裁兼營運長吉姆‧瓦西爾 (Jim Wassil)。

Earlier this afternoon, we issued a news release announcing our results. Copies of this and our other news releases, latest 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，我們發布了新聞稿，宣布了我們的結果。本新聞稿以及我們的其他新聞稿、最新公司介紹和美國證券交易委員會 (SEC) 文件的副本可在我們網站的「投資者和媒體」部分找到。

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.

在我們開始之前，我想提醒您，在本次電話會議中，我們將對 Vaxcyte 做出某些前瞻性陳述，這些陳述受各種風險、不確定性和其他因素的影響，可能導致實際結果與任何前瞻性陳述中提及的結果存在重大差異。

For 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, 2024, and any subsequent reports filed with the SEC. With that, I'll turn the call over to Grant Pickering. Grant?

有關這些聲明所涉及的風險和不確定性的討論，請參閱我們今天發布的新聞稿以及我們向美國證券交易委員會提交的最新文件，包括截至 2024 年 12 月 31 日的 10-K 表中列出的風險因素，以及向美國證券交易委員會提交的任何後續報告。說完這些，我將把電話轉給格蘭特‧皮克林 (Grant Pickering)。授予？

Thanks, Andrew. And all of you on the call and webcast, thank you for joining us today. Vaccines are one of the most powerful innovations in modern medicine, transforming public health by preventing disease, reducing hospitalizations and saving millions of lives every year.

謝謝，安德魯。感謝電話會議和網路直播中的各位嘉賓今天的到來。疫苗是現代醫學中最強大的創新之一，它透過預防疾病、減少住院治療和每年挽救數百萬人的生命來改變公共衛生。

Beyond protecting individuals, vaccines are essential to global health security, curbing outbreaks, alleviating pressure on health care systems and delivering substantial economic benefits by reducing the significant financial burden of infectious diseases. This outsized impact is particularly critical for bacterial infections, where vaccines play a key role in reducing antibiotic use and combating the growing threat of antimicrobial resistance, or AMR, one of the most pressing public health challenges of our time.

除了保護個人之外，疫苗對於全球衛生安全、遏制疫情、緩解醫療系統壓力以及透過減少傳染病帶來的巨大經濟負擔來產生巨大的經濟效益也至關重要。這種巨大的影響對於細菌感染尤其重要，疫苗在減少抗生素使用和對抗日益嚴重的抗生素抗藥性（AMR）威脅方面發揮關鍵作用，而抗生素抗藥性是我們這個時代最緊迫的公共衛生挑戰之一。

Against this backdrop, 2024 was a defining year for Vaxcyte as we continue to advance our mission to protect humankind from the devastating impact of bacterial diseases, including invasive pneumococcal disease or IPD. While pneumococcal conjugate vaccines or PCVs have long been an important element of global immunization programs, our vision extends beyond pneumococcal vaccines.

在此背景下，2024 年對 Vaxcyte 來說是決定性的一年，因為我們將繼續推進我們的使命，保護人類免受細菌性疾病（包括侵襲性肺炎球菌疾病或 IPD）的毀滅性影響。雖然肺炎鏈球菌結合疫苗（PCV）長期以來一直是全球免疫計畫的重要組成部分，但我們的願景並不局限於肺炎鏈球菌疫苗。

We are building a robust pipeline of novel broad-spectrum vaccines designed to address some of the world's most widespread bacterial threats, including Group A Strep, Periodontitis and Shigella. These programs alongside our PCVs reinforce our commitment to delivering life-saving vaccines that can have a meaningful impact on public health.

我們正在建構一系列新型廣譜疫苗，旨在應對世界上一些最普遍的細菌威脅，包括 A 型鏈球菌、牙周炎和志賀氏菌。這些項目與我們的預防性疫苗 (PCV) 一起強化了我們提供能夠對公眾健康產生重大影響的救命疫苗的承諾。

As we continue to advance our pipeline, our PCV franchise remains the cornerstone of our efforts to address one of the most persistent and deadly bacterial threats today. The global pneumococcal vaccine market currently valued at approximately $8 billion in annual sales, continues to expand with the adult segment poised to grow significantly, driven by expanded vaccination guidelines in the US and in other developed countries. The Infant segment remains the largest piece of the market today at an estimated $6 billion in annual sales.

隨著我們不斷推進產品線的建設，我們的 PCV 特許經營權仍然是我們應對當今最持久和最致命的細菌威脅之一的基石。目前，全球肺炎鏈球菌疫苗市場年銷售額約 80 億美元，該市場持續擴大，其中成人市場將大幅成長，這得益於美國和其他已開發國家擴大疫苗接種指南的推動。嬰兒市場目前仍是最大的市場，年銷售額估計為 60 億美元。

However, despite decades of vaccination efforts, it is estimated that Streptococcus pneumoniae accounts for about 300,000 deaths globally each year in children under five years old and remains a leading cause of vaccine preventable deaths in this age group. In the US alone, more than 150,000 hospitalizations occur annually due to pneumococcal pneumonia, underscoring the urgent need for broader spectrum coverage.

然而，儘管經過數十年的疫苗接種努力，據估計，肺炎鏈球菌每年在全球造成約 30 萬名五歲以下兒童死亡，並且仍然是該年齡段兒童可透過疫苗預防死亡的主要原因。光是在美國，每年就有超過 15 萬人因肺炎鏈球菌肺炎而住院，這凸顯了對更廣泛覆蓋的迫切需求。

Over the past year, our team has made meaningful progress in the clinic across our PCV franchise in the pediatric and adult populations. The pinnacle achievement for Vaxcyte in 2024 was the stellar VAX-31 clinical data in adults. In September, we announced those top line results comparing VAX-31 to PCV20 in healthy adults aged 50 and older.

在過去的一年裡，我們的團隊在兒科和成人族群的 PCV 特許經營診所取得了有意義的進展。Vaxcyte 在 2024 年取得的最高成就是 VAX-31 在成人中取得了出色的臨床數據。9 月，我們公佈了針對 50 歲及以上健康成年人的 VAX-31 與 PCV20 的比較結果。

We believe these results validate the potential of our site-specific carrier-sparing platform to deliver the broadest spectrum PCVs, providing protection against both currently circulating and historically prevalent serotypes. Based on the robust strength of this data, we are advancing VAX-31 into a Phase III program for adults. We are also encouraged by our progress in infants with the VAX-24 study fully enrolled and data expected by the end of this quarter and the VAX-31 infant program underway with the first key data set expected in mid-2026.

我們相信，這些結果驗證了我們針對特定部位的載體保留平台提供最廣譜 PCV 的潛力，從而提供對當前流通和歷史上流行的血清型的保護。基於這些數據的強大力量，我們正在將 VAX-31 推進到針對成人的 III 期計劃。我們也對嬰兒研究的進展感到鼓舞，VAX-24 研究已完全入組，預計將於本季度末獲得數據，VAX-31 嬰兒計劃正在進行中，預計將於 2026 年中期獲得第一個關鍵數據集。

Beyond our PCV franchise, we continue advancing our early-stage vaccine candidates that address diseases that contribute significantly to AMR, which is a global health crisis that, if left unaddressed, is expected to become one of the leading causes of death by 2050. While no single solution can fully address AMR, vaccines play a critical role in reducing reliance on antibiotics.

除了 PCV 特許經營權之外，我們還將繼續推進早期候選疫苗，以應對導致抗菌藥物抗藥性 (AMR) 的重大疾病。抗菌藥物抗藥性是一場全球健康危機，如果不加以解決，預計到 2050 年將成為主要死亡原因之一。雖然沒有單一的解決方案可以完全解決抗菌藥物抗藥性問題，但疫苗在減少對抗生素的依賴方面發揮關鍵作用。

We are incredibly proud to be at the forefront of developing vaccines that target drug-resistant pathogens, and we look forward to providing further updates on our pipeline throughout the year. Our clinical progress continues to be driven by strong operational execution, including manufacturing scale-up. As part of our long-standing partnership with Lonza, we are executing on our plan to establish a purpose-built, large-scale manufacturing suite within Lonza's Ibex Dedicated Biopark.

我們非常自豪能夠站在開發針對抗藥性病原體的疫苗的前沿，我們期待全年提供關於我們的研發管道的進一步更新。我們的臨床進展持續受到強大的營運執行力（包括製造規模擴大）的推動。作為我們與 Lonza 長期合作的一部分，我們正在執行計劃，在 Lonza 的 Ibex 專用生物園區內建立一個專門建造的大型製造套件。

The build-out of this dedicated facility began in late 2023 and remains on track to be completed by early next year. This facility will play a critical role in supporting the future of global commercial supply for both the adult and pediatric indications, ensuring we have the capacity to meet anticipated demand.

該專用設施的建設於 2023 年底開始，預計明年年初完工。該設施將在支持未來成人和兒科適應症的全球商業供應方面發揮關鍵作用，確保我們有能力滿足預期的需求。

Also, as a reminder, we are leveraging our existing manufacturing infrastructure with Lonza to support the anticipated US launch of VAX-31 for the adult population. With this foundation in place, we are well prepared to execute on our plans and bring broad spectrum vaccines to market. Our ability to advance these programs is underpinned by a strong financial position, ensuring we have the resources to advance clinical development, scale manufacturing and drive commercialization.

另外，需要提醒的是，我們正在利用與 Lonza 合作的現有製造基礎設施來支援美國針對成年人口推出的 VAX-31。有了這個基礎，我們就可以做好充分準備執行我們的計劃，將廣譜疫苗推向市場。強大的財務狀況是我們推動這些項目的能力的基礎，確保我們擁有推動臨床開發、擴大生產規模和推動商業化的資源。

To provide more details on our financial strength and outlook, I'll now turn it over to Andrew.

為了提供有關我們的財務實力和前景的更多詳細信息，我現在將話題交給安德魯。

Thanks, Grant. The details of our fourth quarter and full-year 2024 results and the reasons for the variances to the comparable 2023 periods are reflected in our 10-K filing and summarized in today's press release. Vaxcyte's financial position remains strong with $3.13 billion in cash, cash equivalents and investments as of December 31, 2024, which includes $2.2 billion in net proceeds from the two successful follow-on equity offerings last year.

謝謝，格蘭特。我們的 2024 年第四季和全年業績詳情以及與 2023 年可比期間差異的原因已反映在我們的 10-K 文件中，並在今天的新聞稿中進行了總結。Vaxcyte 的財務狀況依然強勁，截至 2024 年 12 月 31 日，其現金、現金等價物和投資為 31.3 億美元，其中包括去年兩次成功的後續股票發行所得的 22 億美元淨收益。

Turning to the income statement. The increase in R&D expenses in 2024 was due primarily to increased development and manufacturing activities in connection with the adult and infant PCV programs, including to support the potential future commercial launches as well as growth in R&D personnel. The increase in G&A expenses was driven primarily by higher personnel costs due to the growth in the number of employees in these functions.

轉向損益表。2024 年研發費用的增加主要是由於與成人和嬰兒 PCV 項目相關的開發和製造活動的增加，包括支持未來潛在的商業發布以及研發人員的成長。一般及行政費用的增加主要是由於這些職能部門員工數量的增加導致人員成本上升。

For the build-out of the dedicated manufacturing suite at Lonza to support the potential global launch of our PCV programs, Vaxcyte incurred an additional $127.8 million in capital and facility expenditures last year, bringing the project to-date total to $214.3 million, about 60% to 70% of our original $300 million to $350 million estimate to which we continue to track.

為了在 Lonza 建造專用製造套件以支持我們 PCV 項目的潛在全球發布，Vaxcyte 去年額外花費了 1.278 億美元的資本和設施支出，使該項目迄今為止的總額達到 2.143 億美元，約占我們最初 3 億至 3.5 億美元估計值的 60% 至 70%，我們將繼續跟踪這一估計值。

As we look ahead, we expect a substantial increase in both R&D and G&A expenses in 2025, particularly within R&D over both full year and Q4 2024 annualized levels. This expected increase is primarily the result of manufacturing-related investments to prepare for our initial launch in the adult market, including to build inventory, the initiation of the VAX-31 adult Phase III clinical program and the growth in the number of our employees to support these and other initiatives.

展望未來，我們預計 2025 年研發和一般及行政費用都將大幅增加，尤其是研發費用將超過 2024 年全年和第四季的年化水準。這一預期成長主要源於與製造相關的投資，為首次進軍成人市場做準備，包括建立庫存、啟動 VAX-31 成人 III 期臨床計劃以及增加員工數量以支持這些計劃和其他計劃。

Consistent with historical results, we expect R&D expenses to fluctuate by quarter, largely based on the timing of manufacturing activities. The significant majority of the costs related to the construction and build-out of the dedicated manufacturing suite will not run through the income statement and instead will continue to be reflected on our balance sheet in two separate line items, property and equipment and other assets.

與歷史結果一致，我們預計研發費用將按季度波動，這主要取決於製造活動的時間。與專用製造套件的建造和擴建相關的絕大部分成本將不會計入損益表，而是將繼續反映在我們的資產負債表的兩個單獨項目中，即財產和設備以及其他資產。

Once the build-out is complete and manufacturing activities commence, the costs will then run through the income statement. Turning to cash runway. We expect that our cash, cash equivalents and investments, which, as I noted, totaled $3.13 billion as of 2024 year-end will be sufficient to fund our operating expenses and capital expenditure requirements through several expected key milestones over the next few years.

一旦建設完成並且製造活動開始，成本就會計入損益表。轉向現金跑道。我們預計，我們的現金、現金等價物和投資（正如我所指出的，截至 2024 年底總計 31.3 億美元）將足以滿足我們未來幾年幾個預期關鍵里程碑的營運費用和資本支出需求。

These include: the VAX-24 infant Phase II study primary series and booster dose data readouts; the initiation, completion and data readouts from all of the anticipated Phase III studies for the VAX-31 adult Phase III program; the VAX-31 infant Phase II study primary series and booster dose readouts; and the completion of the build-out of the dedicated manufacturing suite at Lonza.

這些包括：VAX-24 嬰兒 II 期研究的主要係列和加強劑量數據讀數；VAX-31 成人 III 期計劃的所有預期 III 期研究的啟動、完成和數據讀數；VAX-31 嬰兒 II 期研究的主要係列和加強劑量讀數；以及 Lonza 專用製造套件的建成。

We remain committed to financial discipline and to making strategic investments that maximize long-term impact and the steps we are taking today position us for sustainable and meaningful growth. Beyond financial and operational execution, 2024 also marked the establishment of a dedicated public affairs function, enhancing our engagement with policymakers and public health stakeholders.

我們將繼續恪守財務紀律，致力於進行策略性投資，以最大程度地發揮長期影響力，而我們今天採取的措施將使我們實現可持續且有意義的成長。除了財務和營運執行之外，2024 年還標誌著專門公共事務職能的建立，加強了我們與政策制定者和公共衛生利益相關者的合作。

We have been working constructively with the new administration to ensure that science-driven evidence-based policies continue to guide vaccine development and public health decision-making. In parallel, we will continue to engage with the FDA, CDC and ACIP to foster a regulatory framework that continues to encourage investment in vaccine innovation and manufacturing.

我們一直在與新政府進行建設性合作，以確保以科學為依據的實證政策繼續指導疫苗開發和公共衛生決策。同時，我們將繼續與 FDA、CDC 和 ACIP 合作，建立一個持續鼓勵對疫苗創新和製造進行投資的監管框架。

During our engagement with key government stakeholders, we have been encouraged by bipartisan acknowledgment that vaccines are not only a cornerstone of public health, but also one of the most cost-effective interventions available. It is estimated that vaccination in children over the last 30 years in the US will result in direct savings of $540 billion and societal savings of $2.7 trillion.

在與政府主要利害關係人接觸期間，我們受到兩黨一致認可的鼓舞，即疫苗不僅是公共衛生的基石，也是最具成本效益的干預措施之一。據估計，美國過去30年對兒童接種疫苗將直接節省5,400億美元，並為社會節省2.7兆美元。

And expanding vaccine uptake among adults is equally important as vaccine preventable diseases cost the US economy an estimated $27 billion annually in direct and indirect expenses. At Vaxcyte, our mission remains clear, to deliver broad spectrum vaccines that address significant unmet needs. We are confident in the strength of our science and the broad understanding of the critical role vaccines play in protecting global health.

擴大成年人的疫苗接種也同樣重要，因為疫苗可預防疾病每年對美國經濟造成的直接和間接損失估計達 270 億美元。在 Vaxcyte，我們的使命始終明確，即提供廣譜疫苗，滿足尚未滿足的重大需求。我們對我們的科學實力以及對疫苗在保護全球健康方面發揮的關鍵作用的廣泛理解充滿信心。

I will now turn it over to Jim for additional commentary on our clinical development highlights and the upcoming VAX-24 infant study data readout.

現在，我將把主題交給 Jim，請他對我們的臨床開發亮點和即將發布的 VAX-24 嬰兒研究數據讀數進行進一步評論。

Thanks, Andrew. Our PCV franchise continues to advance with major clinical, regulatory and manufacturing milestones, reinforcing our leadership position in pneumococcal vaccine innovation. Over the past year, we have made strong clinical progress across both the adult and infant programs with compelling data in adults supporting the potential to set a new standard in disease coverage with our carrier-sparing platform.

謝謝，安德魯。我們的 PCV 特許經營權繼續向前發展，取得了重大的臨床、監管和製造里程碑，鞏固了我們在肺炎球菌疫苗創新方面的領導地位。在過去的一年裡，我們在成人和嬰兒計畫上都取得了顯著的臨床進展，成人計畫中令人信服的數據支持我們利用攜帶者保留平台在疾病覆蓋方面樹立新標準的潛力。

For the adult indication, VAX-31 delivered strong results in its Phase I/II study, demonstrating robust opsonophagocytic activity or OPA responses across all 31 serotypes. VAX-31 was observed to be well tolerated and demonstrated a safety profile similar to PCV20 at all doses studied through the full six-month evaluation period. The middle and high dose of VAX-31 met or exceeded the non-inferiority criteria for all 20 serotypes shared with PCV20.

對於成人適應症，VAX-31 在其 I/II 期研究中取得了強勁的結果，證明了所有 31 种血清型均具有強大的吞噬活性或 OPA 反應。觀察發現，VAX-31 耐受性良好，並且在整個六個月的評估期內，所有研究劑量下的安全性均與 PCV20 相似。VAX-31 的中劑量和高劑量達到或超過了與 PCV20 共享的所有 20 种血清型的非劣效性標準。

At the VAX-31 high dose, average OPA immune responses were greater for 18 of 20 serotypes compared to PCV20, with seven of these serotypes achieving statistically higher immune responses. At the middle dose, OPA responses were greater for 13 of 20 serotypes and five serotypes achieved statistically higher responses compared to PCV20.

在 VAX-31 高劑量下，20 种血清型中的 18 种血清型的平均 OPA 免疫反應高於 PCV20，其中 7 种血清型實現了統計上更高的免疫反應。在中等劑量下，20 种血清型中有 13 種的 OPA 反應較大，並且與 PCV20 相比，5 种血清型獲得了統計學上更高的反應。

Additionally, all 11 serotypes unique to VAX-31 met the superiority criteria at all dose levels, reinforcing the potential for VAX-31 to deliver the broadest spectrum protection to date. Based on these results, in November 2024, the FDA granted breakthrough therapy designation for VAX-31 in adults, recognizing its potential to set a new standard in pneumococcal disease prevention.

此外，VAX-31 獨有的所有 11 种血清型均符合所有劑量水平的優越性標準，增強了 VAX-31 提供迄今為止最廣譜保護的潛力。基於這些結果，FDA 於 2024 年 11 月授予 VAX-31 成人突破性療法認定，認可其在肺炎球菌疾病預防方面樹立新標準的潛力。

This designation unlocks expedited regulatory pathways with more frequent and senior FDA engagement, potentially streamlining our progression towards launch. Pending an end of Phase II meeting with the FDA, we remain on track to initiate the VAX-31 adult Phase III pivotal non-inferiority study by mid-2025 with top line safety, tolerability and immunogenicity data expected in 2026.

此項指定將開啟快速監管途徑，使 FDA 能夠更頻繁、更資深地參與，從而有可能簡化我們的上市進程。在等待 FDA 的第二階段會議結束之前，我們仍有望在 2025 年中期啟動 VAX-31 成人第三階段關鍵非劣效性研究，預計在 2026 年獲得頂級安全性、耐受性和免疫原性數據。

We also anticipate initiating the remaining Phase III studies for VAX-31 in 2025 and 2026 with the last of the studies to enable a BLA submission expected to read out in 2027. For the infant indication, we continue to advance both the VAX-24 and VAX-31 programs in parallel. In March of last year, we completed enrollment for the Phase II study of VAX-24 in healthy infants, enrolling a total of 802 participants in a two-stage study designed to evaluate safety, tolerability and immunogenicity.

我們也預計將於 2025 年和 2026 年啟動 VAX-31 剩餘的 III 期研究，其中最後一項研究預計將於 2027 年完成 BLA 提交。對於嬰兒適應症，我們繼續同時推進 VAX-24 和 VAX-31 計畫。去年3月，我們完成了VAX-24在健康嬰兒中的II期臨床研究的招募，共招募了802名參與者，進行了旨在評估安全性、耐受性和免疫原性的兩階段研究。

By the end of this quarter, we expect top line data from the primary immunization series comprising the first three doses administered in the first 6 months of life, with data from the booster dose administered at 12 to 15 months of age anticipated by the end of this year. As you will recall, the primary immunization series, which is referred to as post-dose three, serves as a critical indicator of disease protection during the infants vulnerable first year.

到本季末，我們預計將獲得由出生後前 6 個月接種的前三劑疫苗組成的初級免疫系列的頂線數據，並預計在今年年底獲得出生後 12 至 15 個月接種的加強劑疫苗的數據。您可能還記得，初級免疫系列（稱為第三劑後）是嬰兒脆弱的第一年期間疾病防護的關鍵指標。

The booster referred to as post-dose four evaluates anticipated durability of protection through the first few years of life, ensuring sustained immune protection during this heightened period of risk to pneumococcal disease. In this study and for all precedent infant PCV studies, the primary immunogenicity endpoints, both post-dose three and post-dose four are based on immunoglobulin G or IgG antibody concentration, whereas in adult PCV studies, the primary immunogenicity endpoint is OPA.

被稱為第四劑後的加強劑評估了生命最初幾年內預期的保護持久性，確保在肺炎球菌疾病風險較高的時期內持續提供免疫保護。在本研究以及所有先前的嬰兒 PCV 研究中，主要免疫原性終點（第三次給藥後和第四次給藥後）均基於免疫球蛋白 G 或 IgG 抗體濃度，而在成人 PCV 研究中，主要免疫原性終點是 OPA。

This VAX-24 infant study is evaluating the IgG responses compared to PCV20. For the 20 serotypes common with PCV20, the primary endpoint post-dose three is based on the percent of participants who achieved the predefined IgG concentration threshold of greater than or equal to 0.35 micrograms per ml.

這項 VAX-24 嬰兒研究正在評估與 PCV20 相比的 IgG 反應。對於 PCV20 常見的 20 种血清型，第三次給藥後的主要終點是基於達到預定 IgG 濃度閾值（大於或等於每毫升 0.35 微克）的參與者百分比。

This represents the seroconversion rate. To meet the historical non-inferiority requirement in the Phase III trial, the lower bound of the [95th percent confidence] must be within 10 percentage points of the PCV20 seroconversion rate on a serotype-by-serotype basis. Based on precedent PCV programs, the four incremental serotypes unique to VAX-24 will be compared to the lowest performing PCV20 serotype other than serotype three.

這代表血清轉換率。為了滿足 III 期試驗中的歷史非劣效性要求，[95% 置信度] 的下限必須在各個血清型的 PCV20 血清轉換率的 10 個百分點以內。根據先前的 PCV 計劃，VAX-24 獨有的四種增量血清型將與除血清型三之外表現最低的 PCV20 血清型進行比較。

In Phase II studies for which the composite intervals are wider due to a smaller sample size compared to a Phase III trial, sponsors have considered non-inferiority success to be a 15 percentage point differential. We feel encouraged as we head into the infant clinical data readout based on the strength of the data from our three adult clinical studies, including the higher immune responses relative to PCV20, the historical translation of adult to infant data, and the precedent regulatory approval bar.

在 II 期研究中，由於樣本量比 III 期試驗小，因此綜合間隔更寬，申辦方認為非劣效性成功率為 15 個百分點的差異。當我們基於三項成人臨床研究的數據強度進入嬰兒臨床數據讀數時，我們感到鼓舞，包括相對於 PCV20 的更高的免疫反應、成人到嬰兒數據的歷史翻譯以及先例監管批准禁令。

With each iteration of approved PCVs, there have been misses on the noninferiority bar for individual serotypes, up to six misses in the case of PCV20. In our case, we would be disappointed with this type of outcome. However, given this is a proof-of-concept dose-finding study, the purpose of which is to determine the dose and the design of a Phase III program, it is reasonable to expect a few non-inferiority misses.

隨著批准的 PCV 的每次迭代，個別血清型的非劣效性標準都會出現偏差，PCV20 的偏差高達六次。就我們而言，我們會對這種結果感到失望。然而，鑑於這是一項概念驗證劑量探索研究，其目的是確定劑量和 III 期方案的設計，因此預計會出現一些非劣效性錯誤。

Even in this scenario, we would still expect VAX-24 to be well positioned to advance to Phase III and demonstrate best-in-class potential, particularly if we see higher immune responses across multiple serotypes as we saw in all of our adult studies. While we await the data from our VAX-24 infant study, we are also making significant progress on our VAX-31 Phase II study in the same population.

即使在這種情況下，我們仍然預期 VAX-24 將能夠順利進入第三階段並展現出一流的潛力，特別是如果我們在所有成人研究中都看到多種血清型的更高免疫反應。在我們等待 VAX-24 嬰兒研究數據的同時，我們針對同一族群的 VAX-31 第二階段研究也取得了重大進展。

Following its initiation in December 2024, Stage 1 of the study used the dose escalation approach to evaluate the safety and tolerability for the low, middle and high doses. In early February, we advanced to Stage two based on a blinded safety assessment, marking an important milestone in the study's progression.

研究的第一階段於 2024 年 12 月啟動，採用劑量遞增法評估低、中、高劑量的安全性和耐受性。2月初，我們根據盲法安全評估進入第二階段，這是研究進展中的重要里程碑。

We anticipate announcing top line safety, tolerability and immunogenicity data from the primary three-dose immunization series by mid next year with top line booster dose data expected approximately nine months later. Despite the effectiveness of current pneumococcal vaccines, IPD, including meningitis and bacteremia remains persistent in the first years of life.

我們預計明年年中公佈主要三劑免疫系列的頂級安全性、耐受性和免疫原性數據，並預計在大約九個月後公佈頂級加強劑數據。儘管目前的肺炎球菌疫苗有效，但包括腦膜炎和菌血症在內的IPD在生命的最初幾年仍然存在。

The public health community has made it clear that a broader spectrum pneumococcal vaccine is needed to provide expanded protection against this disease. Our PCV programs are designed to address this gap, and VAX-31 has the potential to cover approximately 94% of IPD and 93% of acute otitis media in children under 5, offering significantly greater coverage compared to the standard-of-care PCVs.

公共衛生界已明確表示，需要一種廣譜肺炎球菌疫苗來擴大對這種疾病的保護。我們的 PCV 計劃旨在解決這一差距，VAX-31 有可能涵蓋 5 歲以下兒童約 94% 的 IPD 和 93% 的急性中耳炎，與標準護理 PCV 相比，覆蓋範圍要大得多。

Outside of our PCV programs, we remain focused on advancing our pipeline, including VAX-A1 for Group A Strep, our most advanced pipeline program. Group A Strep is a leading global cause of infectious disease-related death and disability and a major driver of antibiotic prescriptions in young children, underscoring the urgent need for a preventative solution.

在我們的 PCV 專案之外，我們仍然專注於推進我們的產品線，包括 A 型鏈球菌的 VAX-A1，這是我們最先進的產品線專案。A 型鏈球菌是全球傳染病相關死亡和殘疾的主要原因，也是兒童服用抗生素的主要原因，凸顯了預防性解決方案的迫切需求。

As VAX-A1 advances towards the clinic, we have continued to progress activities, including analytical method development, immunological assays and process scale-up for the production of GMP-grade drug substance and drug product. We will provide updates on our anticipated time line as this program advances.

隨著 VAX-A1 進入臨床階段，我們繼續推進相關活動，包括分析方法開發、免疫學測定和 GMP 級藥物物質和藥物產品的生產流程擴大。隨著該計劃的進展，我們將提供預期時間表的更新。

Across all of our programs, our commitment to vaccine innovation remains unwavering. With a strong foundation in place, we are well positioned to drive our pipeline forward, achieving key clinical milestones and accelerate progress towards launch. I'll now turn it back to Grant to share closing remarks.

在我們所有的項目中，我們對疫苗創新的承諾始終堅定不移。憑藉堅實的基礎，我們有能力推動我們的產品線向前發展，實現關鍵的臨床里程碑並加快產品上市的進程。現在我請格蘭特作最後發言。

Thanks, Jim. Before moving to Q&A, I want to express my deep gratitude to our investors; partners; clinical trial participants; and most importantly, our employees. Your support, dedication and belief in our mission continue to propel Vaxcyte forward as we work to develop vaccines that address some of the most pressing unmet needs in bacterial diseases.

謝謝，吉姆。在進入問答環節之前，我想向我們的投資者、合作夥伴、臨床試驗參與者以及最重要的我們的員工表示深深的感謝。我們致力於開發疫苗，解決細菌性疾病中一些最迫切的未滿足需求，您的支持、奉獻和對我們使命的信任將繼續推動 Vaxcyte 前進。

With the strength of our science, the dedication of our team and the momentum we've built, we are well positioned to execute on our vision and deliver meaningful impact. As we look ahead to the rest of the year, we do so with confidence and optimism. This will be a milestone-rich year marked by key clinical and regulatory advancements, continued expansion of our manufacturing capabilities and the next steps in building a global platform for vaccine innovation.

憑藉我們科學的實力、團隊的奉獻精神以及我們所建立的勢頭，我們完全有能力實現我們的願景並產生有意義的影響。展望今年剩餘時間，我們充滿信心和樂觀。這將是具有里程碑意義的一年，標誌著關鍵的臨床和監管進展、我們製造能力的持續擴大以及建立全球疫苗創新平台的後續步驟。

With a strong foundation in place, we are poised to drive Vaxcyte's next phase of growth and ultimately bring life-saving vaccines to those who need the most. We appreciate your interest and look forward to sharing further updates as the year progresses. With that, let's take some questions. Operator?

憑藉著堅實的基礎，我們準備推動 Vaxcyte 的下一階段成長，並最終為最需要的人提供救命的疫苗。我們感謝您的關注，並期待在未來分享進一步的更新。接下來，我們來回答一些問題。操作員？

(Operator instructions)

（操作員指示）

Roger Song, Jefferies.

傑富瑞 (Jefferies) 的羅傑宋 (Roger Song)。

Great, thanks for the update and congrats for all the progress. A couple of questions from us. So the first one is regarding the Phase II VAX-24 infant primary series data readout. Can you just give us some color around what factors play into the timing of the data readout given you already finished the enrollment by 1Q last year? And then how should we think about how much safety data you will provide? And then all the immunogenicity data will be analyzed by the time -- by the end of 1Q this year?

太好了，感謝您的更新，並祝賀您取得的所有進展。我們有幾個問題。第一個是關於第二階段 VAX-24 嬰兒初級系列資料讀數。鑑於您去年第一季就已經完成了招生，您能否向我們詳細說明哪些因素會影響資料讀取的時間？那麼我們應該如何考慮您將提供多少安全資料？然後，所有免疫原性數據都會在今年第一季末進行分析嗎？

Thank you.

謝謝。

Yes. Thanks for the question, Roger. Yes. I mean the primary endpoint for the infant indication, as you know, are actually split across two different co-primary endpoints, the first after post-dose three, the second after post-dose four, and those are all based on the IgG antibody responses.

是的。謝謝你的提問，羅傑。是的。我的意思是，如您所知，嬰兒適應症的主要終點實際上分為兩個不同的共同主要終點，第一個終點是在第三次給藥後，第二個終點是在第四次給藥後，這些都是基於 IgG 抗體反應。

So this is a top line data readout, and this is the standard accrual for the accumulation of those antibody responses. So that's the primary thing that we'll be focused on at this particular occasion. Jim, do you want to comment on the amount of the safety data you'll expect to have by the end of the quarter?

這是頂線資料讀數，也是這些抗體反應累積的標準累積。所以這是我們在這次特定場合關注的主要事項。吉姆，你想評論一下本季末預計會有多少安全資料嗎？

Yes. So we will cut the safety data just prior to when we have all of the prerequisite immunogenicity data. So that will include whatever we have at that point in time. So my expectation is the vast majority of safety data from post primary all the way up to boost will be included. There will be some post boost as well, but that won't be as robust as obviously post primary through Boost.

是的。因此，我們將在獲得所有先決條件免疫原性資料之前截取安全資料。因此這將包括我們當時所擁有的一切。因此，我的期望是，從國中畢業一直到升學的絕大多數安全資料都將被納入其中。後期也會有一些提升，但顯然不會像透過 Boost 進行初次後期提升那樣強勁。

And your second question, Roger?

羅傑，你的第二個問題是？

Yes, if I may. And so for the -- I think on the call, you say if you miss 6 serotypes on the non-inferiority will be disappointed. So that speaks to the confidence. Maybe just -- I think you mentioned something given the Phase II sample size is smaller than the typical Phase III. How should we think about the non-inferiority criteria?

是的，如果可以的話。所以對於——我認為在電話會議上，你說如果你錯過 6 种血清型，非劣效性就會令人失望。這體現了信心。也許只是——我認為您提到了一些事情，因為第二階段的樣本量比典型的第三階段要小。我們該如何看待非劣效性標準？

Maybe just give us a little bit of clarity what we are really looking for. You mentioned 15% point differential. How should we think about that? Is the bar for the lower bound confidence interval? Or what's the -- or it is the point estimate difference?

也許只是讓我們稍微清楚一點我們真正在尋找的是什麼。您提到了 15% 的分差。我們該如何看待這個問題？這是下限信賴區間的標準嗎？或者是什麼——或者它是點估計差異？

Thank you.

謝謝。

Yes. Thanks, Roger. Yes, per the prepared remarks, the precedent for the most broad spectrum PCV to-date, which would be the 20-valent, when they were comparing themselves to the prior standard of care, the 13-valent vaccine, indeed, they actually failed on six of those 13 non -- well, six of the 20 noninferiority comparisons. And yet that was still enough for them to gain full approval and for them to gain the overwhelming market share.

是的。謝謝，羅傑。是的，根據準備好的評論，迄今為止最廣譜 PCV 的先例，即 20 價疫苗，當他們將自己與之前的標準治療方法 13 價疫苗進行比較時，實際上，他們在 13 個非劣效性比較中有 6 個失敗了——好吧，20 個非劣效性比較中有 6 個失敗了。但這仍然足以讓他們獲得充分的認可並獲得壓倒性的市場份額。

So when we look at the data that we've generated across three different adult Phase II clinical studies with VAX-24 and VAX-31, we've shown such consistently higher average immune responses that was not the case for the 20-valent versus the 13-valent, certainly in adults and even more so a widening of a gap with falling immune responses in infants.

因此，當我們查看 VAX-24 和 VAX-31 在三項不同的成人 II 期臨床研究中產生的數據時，我們發現平均免疫反應始終較高，而 20 價疫苗與 13 價疫苗則並非如此，這在成人中尤為明顯，在嬰兒中，隨著免疫反應下降，差距進一步擴大。

And so, our view is that given the continuity of immune responses from adults to infants affords us the confidence to expect a better outcome. So of course, we're comparing with the 24-valent vaccine. So we'll see precisely what our immune responses are on a relative basis. But indeed, we would be surprised to the negative if we were to have seen as many misses as they saw.

因此，我們的觀點是，鑑於從成人到嬰兒的免疫反應的連續性，我們有信心期待更好的結果。因此，我們當然是在與 24 價疫苗進行比較。因此，我們將準確地了解我們的免疫反應相對情況。但事實上，如果我們看到和他們一樣多的失誤，我們會感到很驚訝。

So we're expecting something more bullish. We could imagine missing on a few. But on the other hand, if we did, we would expect perhaps at least that many with higher immune responses given [later on] in the adult setting. So that is one feature. But then to your point, the other thing in drug development for pneumococcal conjugate vaccines is the size of the study, particularly when you're doing your dose ranging is considerably smaller than the ultimate Phase III pivotal non-inferior study that would need to be conducted.

因此，我們期待出現更樂觀的走勢。我們可以想像會錯過一些。但另一方面，如果我們這樣做了，我們預期在成人環境中，至少會有這麼多人表現出更高的免疫反應。這是一個特點。但回到您的觀點，肺炎鏈球菌結合疫苗藥物開發的另一個問題是研究的規模，特別是當您的劑量範圍比需要進行的最終 III 期關鍵非劣效研究小得多時。

So like we had talked about in the adult setting, the sponsors that have come before us and for us going forward, you have a right to take into account the smaller sample size. And the way that's manifested itself in the past is even though the ultimate difference in the absolute rate of seroconversion needs to be within 10 points at Phase III; in Phase II, given how much smaller the studies are, other sponsors before us have considered a 15-point absolute difference as adequate as a predictor of what it will take to hit the endpoint in Phase III.

因此，就像我們在成人環境中討論的那樣，對於在我們之前的贊助商以及我們未來的贊助商來說，您有權考慮較小的樣本量。過去的表現是，儘管在 III 期臨床試驗中，血清轉換絕對率的最終差異需要在 10 個點以內；但在第二期臨床試驗中，考慮到研究規模較小，我們先前的其他申辦者認為 15 個點的絕對差異足以預測達到 III 期臨床試驗終點所需的條件。

So we're going to take a similar approach, knowing that we'll have that same opportunity to take advantage of the much larger sample size, which clearly closes up the confidence intervals at the 10-point absolute difference. So yes, two key features of how to think about this upcoming data. So Roger, thank you for raising both of those.

因此，我們將採取類似的方法，因為我們知道我們將有相同的機會利用更大的樣本量，這顯然會在 10 點絕對差異處縮小置信區間。是的，關於如何看待即將到來的數據有兩個關鍵特徵。所以羅傑，謝謝你提出這兩個問題。

Thank you so much. Very quick last one. Given we are looking for this primary series data, but how should we think about the read-through from the primary series data to the booster, which will be nine months later? Should we have a higher confidence the booster will more likely going to hit even if you have a few misses for the primary?

太感謝了。最後一個非常快。鑑於我們正在尋找這些主要係列數據，但是我們應該如何考慮從主要係列數據到加強器的讀取，這將是九個月後？我們是否應該更有信心，即使在初次發射時有幾次失誤，助推器也更有可能擊中目標？

Thank you.

謝謝。

Yes. So -- and we've been trying to condition the market to appreciate that the two co-primary endpoints are different, right? The first of which is a seroconversion comparison, whereas the second after the fourth dose, the booster is a comparison of the magnitude of immune responses.

是的。所以——我們一直在努力讓市場認識到兩個共同主要終點是不同的，對嗎？其中第一次是血清轉換的比較，而第二次是在第四劑之後的加強劑，是免疫反應強度的比較。

So as everyone knows from our adult data, we've shown a great ability to not only show non-inferior magnitude of immune responses, but in fact, showing in most cases, higher immune responses and in many cases, statistically higher immune responses. So we've really thrived on that second comparison that we'll have later this year.

因此，正如大家從我們的成人數據中了解到的那樣，我們不僅表現出了強大的能力，即顯示出非劣勢的免疫反應，而且事實上，在大多數情況下，顯示出更高的免疫反應，並且在許多情況下，在統計上顯示出更高的免疫反應。因此，我們在今年稍後進行的第二次比較中確實取得了成功。

And while the seroconversion data will be the main event with this upcoming data readout, you should expect that will also present those IgG antibody comparisons, which will give us an indication of how to expect the post-dose four data to look. And while it's not the headline for the prior vaccines that are currently marketed, the 15 and the 20, they saw an even more pronounced drop in the magnitude of immune responses at this post-dose three.

雖然血清轉換數據將是即將發布的數據讀數的主要事件，但您應該預料到它還將呈現那些 IgG 抗體比較，這將為我們提供劑量後四次數據預期的樣子的指示。雖然這不是目前市面上銷售的 15 號和 20 號疫苗的亮點，但在接種第三劑後，它們的免疫反應幅度出現了更明顯的下降。

So if we reverse that trend as we did with adults, not only would it indicate that we've done quite well on the initial seroconversion, but it would also set us up for confidence heading into the next data point at the end of the year.

因此，如果我們像對成年人一樣扭轉這一趨勢，這不僅表明我們在最初的血清轉換方面做得相當好，而且還為我們在年底進入下一個數據點時樹立了信心。

Salim Syed, Mizuho.

薩利姆賽義德，瑞穗。

Great, thanks for all the color guys and congrats on the progress. I wanted to spend a little bit of time just focusing on the macro discussion, just kind of given that's had such a heavy impact on the stock in the 4Q and 1Q. Totally appreciate the commentary in the prepared remarks about the conversations being constructive with DC. But could you perhaps give us a little bit more granularity there, if possible, as it relates to whether there have been actually discussions with distinction to PCVs versus other vaccines, how we should interpret this last ACIP meeting delay or any other particular granularities there?

太好了，感謝所有的色彩師，並祝賀你們的進步。我想花一點時間專注於宏觀討論，因為這對第四季和第一季的股票產生了很大的影響。非常感謝您在準備好的評論中提到與華盛頓特區的對話具有建設性。但是，如果可能的話，您能否更詳細地談談，例如是否真的就PCV疫苗與其他疫苗的區別進行過討論，我們應該如何解讀上次ACIP會議的延期，或者其他任何具體細節？

Thank you.

謝謝。

Yes. I think Andrew and I can tag team this one. I'll start and then let Andrew jump in. But just taking up that last topic and the ACIP delay, I mean, I think one of the things that was not widely reported was that as a matter of course, for every ACIP meeting historically, there is an opportunity for public comment. And no one knows precisely why it happened.

是的。我認為安德魯和我可以組隊參加這個比賽。我先開始，然後讓安德魯加入。但是，僅討論最後一個主題和 ACIP 延遲，我的意思是，我認為沒有被廣泛報道的事情之一是，理所當然地，從歷史上看，每次 ACIP 會議都有機會發表公眾評論。沒有人知道這件事發生的具體原因。

I think it was -- I think people believe it was inadvertent. But somehow in early February, that public commentary mechanism was not opened up. So that would have been atypical to not allow for that. So it could be as simple as that, and that is what is precipitating that delay.

我認為這是——我認為人們認為這是無意的。但不知何故，2月初，該公眾評論機制並未開放。因此，如果不允許這樣做，那就不正常了。事情可能就是這麼簡單，而這正是延遲的原因。

I don't think people should overread into that situation. But there is a lot going on. Andrew is right in the thick of it. Maybe you can take up the first two conversations as it relates to PCV vaccines being implicated and just the macro discussion at large.

我認為人們不應該過度解讀這種情況。但還有很多事情發生。安德魯正處於此事的中心。也許您可以討論前兩次與 PCV 疫苗有關的對話以及宏觀討論。

Yes. No, Salim, I appreciate the question. As many of you on this call know, this is something we've been actively following and actively engaged in, as I noted in the prepared remarks. Yes, Salim, we aren't commenting on the very specifics of the folks with whom we've had discussions.

是的。不，薩利姆，我很感謝你提出這個問題。正如我在準備好的演講中提到的那樣，這次電話會議中的許多人都知道，這是我們一直積極關注和積極參與的事情。是的，薩利姆，我們不會對與我們討論的人的具體情況發表評論。

But as I said in the prepared remarks, not only are we active, but we've been encouraged by truly bipartisan support for the important role vaccines play in public health in addition to, obviously, the health benefit, the significant economic benefit given the cost effectiveness of these vaccines.

但正如我在準備好的發言中所說，我們不僅積極行動，而且兩黨真正支持疫苗在公共衛生中的重要作用，這讓我們感到鼓舞，此外，顯然，疫苗還具有健康益處，考慮到這些疫苗的成本效益，還具有顯著的經濟效益。

And as we've said, it is our view and continues to be our view that PCVs are the bedrock of our immunization programs, particularly in the infant population. And so we'll continue to monitor things. We'll continue to stay engaged. We'll continue to stay active. But I do think there is broad understanding, as I said, of the important role vaccines play and really no better testament to kind of the demonstrated benefit than that of PCVs over the last 25 years for infants and the last 15 [years] in the adult population.

正如我們所說，我們認為並將繼續認為 PCV 是我們免疫計畫的基石，特別是對於嬰兒群體而言。因此我們會繼續監控事態發展。我們將繼續保持參與。我們將繼續保持活躍。但正如我所說，我確實認為，人們普遍認識到疫苗的重要作用，而且沒有什麼比PCV在過去25年中對嬰兒和過去15年中對成年人的益處更好的證明。

Okay. Cool. And then maybe just to add on to that. Is there anything in particular when you're having these discussions with the folks in D.C., is there anything in particular that sort of comes to life that the market can potentially look at as sort of getting this market over the macro hump that's sort of arisen in the past several months. Is there anything in particular that we should be looking for, you think that the market is missing?

好的。涼爽的。然後也許就只是補充一下。當您與華盛頓的人們進行這些討論時，是否有任何特別的事情可以讓市場看到，從而幫助市場克服過去幾個月出現的宏觀困難。您認為市場缺少什麼，我們應該特別尋找什麼嗎？

Thank you.

謝謝。

Well, I guess I would say we ourselves, we should all just kind of take with caution the noise, if you will, and the news, and there's a lot of it. And there's been speculation and there's been talk. What I think is most important for us and all of us is what ultimately transpires here. And we're certainly doing our best to continue to advocate for the important role vaccines play. So let's -- I've just [hope] not to overreact to noise or potential changes.

好吧，我想我會說我們自己，如果你願意的話，我們都應該謹慎對待噪音和新聞，而且有很多這樣的噪音和新聞。有各種猜測和傳言。我認為對我們所有人來說最重要的是最終在這裡發生的事情。我們當然會盡最大努力繼續倡導疫苗的重要作用。所以讓我們——我只是[希望]不要對噪音或潛在的變化反應過度。

Changes are par for the course in general and certainly in connection with changes in administration. And it's the actions ultimately, if any, that will be the most important thing rather than kind of the words or these discussions about potential changes. So certainly watching it closely. But again, as I said, encouraged by what we have heard and hearing firsthand over the course of our discussions about kind of the support on both sides of the aisle for vaccines.

總體而言，變化是正常的，並且肯定與行政管理的變化有關。最終，行動才是最重要的，而不是言語或關於潛在變化的討論。所以一定會密切注意。但正如我所說，我們在討論過程中親耳聽到的有關雙方對疫苗的支持令我們感到鼓舞。

David Risinger, Leerink Partners.

Leerink Partners 的 David Risinger。

Hey guys, Yes, [Bryan] on for Dave. thanks for the updates and we appreciate you taking our question. We have two, if that's okay. So first, could you provide more color on the expected Phase III program for VAX-31 in adults, including the likely timeline from the initiation in mid-'25 to the top line results in '26. We're just trying to get a sense for approximately how many months do you think it will take after initiation that we might see top line results?

嘿，大家好，是的，[布萊恩] 代替戴夫發言。感謝您的更新，也感謝您回答我們的問題。如果可以的話，我們有兩個。首先，您能否詳細介紹 VAX-31 針對成人的預期 III 期計劃，包括從 25 年中期啟動到 26 年獲得頂線結果的可能時間表。我們只是想了解一下，您認為啟動後大約需要幾個月才能看到頂線結果？

Yes. Maybe I'll start there, and Jim can certainly chime in. Just to remind the guidance that we again reaffirmed today that we would anticipate starting the pivotal non-inferiority study for VAX-31 in adults by middle of this year and to have the top line safety, tolerability and immunogenicity data from that study next year. So that gives you some idea of the timeline from initiation to data.

是的。也許我會從那裡開始，吉姆當然也可以加入。只是為了提醒指導，我們今天再次重申，我們預計將在今年年中開始對成人進行 VAX-31 的關鍵非劣效性研究，並在明年獲得該研究的最高安全性、耐受性和免疫原性數據。這樣您就可以了解從啟動到資料的時間軸。

If you look back at our VAX-24 study, which would be a good kind of comparator, that was 12 to 15 months or so between the initiation of the study and data readout at this juncture, see that have no reason why it would be any different for this study. And then that is one, of course, of a few studies that comprise the Phase III program in total.

如果您回顧我們的 VAX-24 研究，這將是一個很好的比較器，從研究開始到此時數據讀出之間大約有 12 到 15 個月的時間，您會發現沒有理由認為這項研究會有所不同。當然，這只是構成第三階段計劃的幾項研究之一。

And as you saw today, we've just confirmed our pre-existing guidance and just adding some more clarity to it, and we expect the balance of the studies that comprise that Phase III program to start either also this year alongside or along with the noninferiority study or next year, but those studies would read out in either 2026 or 2027. Those studies in general, Bryan, tend to be on par or faster than the non-inferiority study. So give you a sense of kind of the expected timing for those programs.

正如您今天所看到的，我們剛剛確認了我們現有的指導方針，並對其進行了更清晰的說明，我們預計構成該 III 期計劃的其他研究也將於今年或明年與非劣效性研究同時開始，但這些研究將在 2026 年或 2027 年完成。布萊恩，總體而言，這些研究往往與非劣效性研究持平或更快。因此，讓您大致了解這些計劃的預期時間。

Okay. That's super helpful. I appreciate that. And then just one more on your preclinical Group A Strep vaccine. Could you explain why Vaxcyte's technology is well suited to potentially succeed? And how close might this be to IND-enabling studies?

好的。這非常有幫助。我很感激。然後再談一下臨床前 A 型鏈球菌疫苗。您能解釋一下為什麼 Vaxcyte 的技術很有可能會成功嗎？這與 IND 支持研究有多接近？

Yes, I can start on that one. For bacterial vaccines, conjugate vaccines have really been the primary approach that's been effective. So just like we're leveraging with our pneumococcal conjugate vaccines, we have special technology that allows us to perform site-specific conjugation of polysaccharides that are found on the outer coat of the bacteria, and then proteins to drive a memory response to prevent infection and preserve protection against bacteria over a durable period of time.

是的，我可以從那一個開始。對於細菌疫苗，結合疫苗確實是主要且有效的方法。因此，就像我們利用肺炎球菌結合疫苗一樣，我們擁有特殊的技術，可以對細菌外殼上的多醣進行位點特異性結合，然後對蛋白質進行結合，以驅動記憶反應，防止感染並在較長時間內保持對細菌的保護。

So we're leveraging the same fundamental technology that has created a broader spectrum class of pneumococcal conjugate vaccines, which is really what we've become known for. Group A Strep, on the other hand, is a vaccine for which there has never been one developed to-date.

因此，我們利用相同的基礎技術，創造了更廣譜的肺炎球菌結合疫苗，這也是我們真正為人所知的。另一方面，A 型鏈球菌疫苗迄今仍未發展出來。

So there's a novelty feature to this. But it's also an area where there's very little to no competition, so we have an opportunity to be a first mover. We're leveraging an approach that has been effective across a number of different bacterial vaccine targets. We have a proprietary polysaccharide that is resident across the full spectrum of different strains of Group A Strep.

因此，這是一個新穎的功能。但這也是一個競爭很少甚至沒有競爭的領域，所以我們有機會成為先驅。我們正在利用一種對多種不同細菌疫苗目標都有效的方法。我們擁有一種專有的多醣，它存在於 A 型鏈球菌的所有不同菌株中。

That's unique to us, and we're able to site specifically conjugate it to a conserved protein on the surface of this bacteria that is accessible to antibodies to clear the bacteria. So we think we have two ways to win with this particular approach technologically. And then important from a market opportunity, we also have two ways to win to the extent this is a problem that afflicts not only infants and primary school children, but also older adults.

這是我們獨有的，我們能夠將其特異性地結合到細菌表面的保守蛋白質上，抗體可以接觸到該蛋白質以清除細菌。因此，我們認為從技術上來說，我們可以透過兩種方式利用這種特殊方法來取勝。從市場機會來看，重要的是，我們還有兩種方法可以解決這個問題，因為這個問題不僅困擾著嬰兒和小學生，也困擾著老年人。

And in fact, the magnitude of invasive disease afflicting adults by Group A Strep exceeds that of what was accessible for pneumococcal vaccines when they were approved for adults. So it's a really big opportunity for us. We're really gratified to be in the lead in this area.

事實上，A 型鏈球菌對成年人造成的侵襲性疾病的嚴重程度超過了肺炎鏈球菌疫苗獲準用於成年人時所能達到的程度。所以這對我們來說是一個非常大的機會。我們非常高興能夠在這一領域處於領先地位。

We have mentioned further work that we've been doing to complete the VAX-A1 program to get it in the clinic. We're stopping just short of when we're saying that clinical study will get underway. But rest assured, we're getting closer and are excited, and we'll keep everyone updated on our progress there.

我們已經提到了我們為完成 VAX-A1 計劃並使其進入臨床的進一步工作。我們剛剛說過臨床研究即將開始，現在卻停了下來。但請放心，我們正在接近目標並且感到興奮，我們將向大家通報我們的進展。

Umer Raffat, Evercore.

烏默·拉法特（Umer Raffat），Evercore。

Hi guys, can I ask 25 questions like Salim also?

大家好，我可以像 Salim 一樣問 25 個問題嗎？

You can ask 31, Umer.

你可以問31，Umer。

All right. 31, that's a good number. In all seriousness, three quick ones, if I may. First, I realize you mentioned on the call that the non-inferiority margin is 10% delta. I feel like that's the right delta for a registrational trial powered appropriately. Are you being too stringent with the choice of that delta knowing that Merck had used a more wider 15% delta to define noninferiority? That's number one.

好的。 31，這是一個不錯的數字。嚴肅地說，如果可以的話，我想快速問三個問題。首先，我知道您在電話中提到非劣效性邊界是 10% 的增量。我覺得這對於適當驅動的註冊試驗來說是正確的增量。您是否在選擇該增量時過於嚴格，因為您知道默克公司已經使用了更廣泛的 15% 增量來定義非劣效性？這是第一點。

Second, if I just step back and think about it very simplistically, most serotypes, seroconversion rates are 80% to 90% on Prevnar 20, except two, which is serotype three and 12F, where their seroconversion rates are more like 50%. And I guess that's my question to you. Let's say you're noninferior, but you're 40% seroconversion. Is that a successful outcome to you?

其次，如果我退一步並非常簡單地思考一下，大多數血清型在 Prevnar 20 上的血清轉換率為 80% 至 90%，但有兩種除外，即血清型 3 和 12F，它們的血清轉換率更像是 50%。我想這就是我要問您的問題。假設您不劣於其他患者，但血清轉換率為 40%。對您來說這是一個成功的結果嗎？

And I ask because on those two serotypes three and 12, at least in adults on IgG, not OPA, you guys were fairly ahead. And last point, I realize the focus is entirely on post-dose three. Would you happen to have any post-dose four data even if it's in 100 out of the 700 or 800 patients?

我之所以問這個問題，是因為在 3 型和 12 型這兩种血清型上，至少在 IgG 而非 OPA 的成年人中，你們相當領先。最後一點，我意識到重點完全放在第三次服藥後。即使是 700 或 800 名患者中的 100 名，您是否會獲得第四次給藥後的數據？

Thank you very much.

非常感謝。

You've got it exactly right, Umer, the 10% delta is the registration hurdle. And we are not trying to make things more difficult on us than we should. We will look at that same 15-point delta that Merck used when they developed VAXNEUVANCE as the hurdle that we should be looking at for all the right reasons. It's purely because of the wider confidence intervals when you've got a smaller cohort of subjects.

你說得完全正確，Umer，10% 的差異就是註冊障礙。我們並不想讓事情變得比我們應得的更困難。我們將把默克公司在開發 VAXNEUVANCE 時使用的相同的 15 點增量視為我們應該出於所有正確理由關注的障礙。這純粹是因為當你擁有一小群受試者時，信賴區間會更寬。

So we're trying to not only acknowledge where we'll want to be. I guess the point that people will have taken is even with our smaller Phase II studies in adults, we were able to meet the registrational non-inferiority hurdle, but that's a luxury, not a necessity.

因此，我們不僅要了解我們想要達到的目標。我想人們會明白的是，即使我們在成人中進行了規模較小的 II 期研究，我們也能夠滿足註冊非劣效性障礙，但這是一種奢侈，而不是必需品。

We really want to see that 15-point delta exceeded at this stage, and that will guide us to what the sample needs to look like in Phase III to ensure that we could hit the 10-point delta when it matters, which is that pivotal registration study to your point.

我們確實希望看到在此階段超過 15 點增量，這將引導我們了解第三階段的樣本需要是什麼樣子，以確保我們能夠在重要時刻達到 10 點增量，這就是您所說的關鍵註冊研究。

Then as it relates to the second question with regard to the seroconversion rates, Jim, do you want to talk about that? And obviously, Umer is pointing out there were two big laggards for Prevnar 20, but like how are you thinking about that?

那麼關於血清轉換率的第二個問題，吉姆，你想談談嗎？顯然，Umer 指出 Prevnar 20 有兩個很大的落後者，但您是如何看待這一點的？

Yes. No, I think, Umer, as -- I think you're spot on, on your assessment. If you've got greater than 90% seroconversion rate, that means that your GMCs are much higher than the level of the 0.35 level, whereas for serotype three, their GMC is almost the same as the 0.35 level. And so any slight miss on serotype three could have a greater impact on percent of individuals who achieve that protective threshold.

是的。不，我認為，烏默爾，你的評估是正確的。如果您的血清轉換率超過 90%，則表示您的 GMC 遠高於 0.35 水平，而對於血清型三，其 GMC 幾乎與 0.35 水平相同。因此，血清型 3 的任何輕微失誤都可能對達到該保護閾值的個體百分比產生更大的影響。

I do think that given our results in adults so far and with the results of serotype three being higher and there being translatability between adults and infants, I don't expect us to see that type of result. But if we do, we had said before, if we have a few misses, we feel that, that's still a very good product that we can move forward and get approved in the Phase III trials.

我確實認為，鑑於我們迄今為止在成年人中取得的結果，並且血清型三的結果更高，並且成人和嬰兒之間存在可轉化性，我不希望我們看到那種結果。但如果我們這樣做了，我們之前就說過，即使有一些失誤，我們也覺得，這仍然是一個非常好的產品，我們可以繼續前進並在第三階段試驗中獲得批准。

And then to your last question, I think the 31st question that you asked, the PD3 versus PD4 data, we will wait and unblind all that PD4 data in mass. So while we could theoretically look at some cases by the time we got the PD3, that would not make good clinical quality sense. So we'll wait until we get critical mass on that. That's what we'll be able to read out later this year. It will not be cherry-picked.

然後對於您的最後一個問題，我認為您問的第 31 個問題，即 PD3 與 PD4 數據，我們將等待並大規模揭開所有 PD4 數據的神秘面紗。因此，雖然理論上我們可以在獲得 PD3 時查看一些病例，但這對臨床品質沒有好處。因此，我們會等到達到臨界質量。這就是我們今年晚些時候能夠讀出的內容。它不會被挑選出來。

Seamus Fernandez, Guggenheim.

謝默斯·費爾南德斯，古根漢美術館。

Hey guys, thanks for the question. So just a couple of quick ones here. The first question is, the opportunity or if it makes sense at all to consider the possibility of 31 potentially advancing directly to [peds] should -- depending on, obviously, the 24 data and 31 data, is there an opportunity to kind of assess moving that 31 forward?

嘿夥計們，謝謝你的提問。這裡僅簡單介紹幾個。第一個問題是，是否有機會或是否有意義考慮 31 直接晉升到 [peds] 的可能性應該 - 顯然取決於 24 數據和 31 數據，是否有機會評估將 31 向前推進？

Or is there a compelling reason to move both 24 and 31 forward given differences in the sort of international dosing decisions. What would be the decision points that you would be looking at that would be most critical to making that decision? And then the second question is really around this discussion and debate over efficacy studies.

或者，考慮到國際劑量決策的差異，是否有令人信服的理由將 24 和 31 提前。您所考慮的、對於做出該決定最為關鍵的決策點是什麼？第二個問題其實是圍繞著功效研究的討論和辯論。

It seems a bit ridiculous and quite redundant in the pneumococcal space. But there is an efficacy study that the team could conduct in the pediatric setting post approval that could be quite compelling, which is an otitis media opportunity. Hoping you could just kind of put some context around that and what you see as the opportunity for potentially VAX-31 perhaps securing an otitis media claim? And what that study might look like? Thanks so much.

在肺炎球菌領域，這似乎有點荒謬且相當多餘。但是，該團隊可以在藥物核准後在兒科環境中進行一項功效研究，該研究可能非常引人注目，這是一個治療中耳炎的機會。希望您能對此進行一些介紹，以及您認為 VAX-31 可能獲得中耳炎索賠的機會是什麼？那麼這項研究看起來是什麼樣的呢？非常感謝。

Yes. Thanks, Seamus. So your first question was about the VAX-31 versus VAX-24 pivot opportunity in infants. Obviously, we navigated that last year in association with the strength of the VAX-31 data to make it obvious to graduate from VAX-24 to VAX-31 as our singular approach for adults. But in that case, we didn't really have a time delta between the two programs based on how things lined up from a product availability perspective.

是的。謝謝，西莫斯。所以您的第一個問題是關於嬰兒中 VAX-31 與 VAX-24 的樞軸機會。顯然，去年我們結合 VAX-31 數據的強度進行了導航，明確地從 VAX-24 升級到 VAX-31 作為我們針對成年人的單一方法。但在那種情況下，從產品可用性角度來看，我們實際上並沒有在這兩個程序之間建立時間差。

So that was a very straightforward choice. Here we are on the verge of receiving our first pediatric data with VAX-24. As we've declared, we've not waited to get VAX-31 into the clinic in infants. So we have two trains that have left the station. The one is going to get to the next station before the other.

所以這是一個非常直接的選擇。我們即將透過 VAX-24 接收第一批兒科數據。正如我們所宣稱的，我們迫不及待地想將 VAX-31 引入嬰兒臨床。我們已經有兩個火車離開車站了。一個人會比另一個人先到達下一站。

We'll have a period of time where we'll be managing what would be the most broad-spectrum vaccine available to the market at the fastest pace, which would be VAX-24, which, of course, here in the US, the principal competitor would be the 20-valent from Pfizer. But as you point out, in Europe, the 20-valent was not able to meet the European schedule of the two-plus-one approach versus the US schedule where they give an extra vaccination. So the competition in Europe is really the 15-valent.

我們將有一段時間以最快的速度管理市場上最廣譜的疫苗，即 VAX-24，當然，在美國，它的主要競爭對手是輝瑞的 20 價疫苗。但正如您所指出的，在歐洲，20 價疫苗無法滿足歐洲的「二加一」接種計劃，而美國的計劃是額外接種一種疫苗。因此，歐洲的競爭實際上是15價的。

So we do have a winner in our mind for which the data is reading out here shortly. But of course, the VAX-31 data, as we've guided, we're expecting to get that data by the middle of next year. So it is not far behind VAX-24. So once we receive that VAX-24 data, we'll be able to better handicap how much headroom there was for the 31 valent to be effective.

因此，我們心中確實有一個贏家，其數據很快就會公佈。但當然，正如我們所指導的那樣，我們預計將在明年年中之前獲得 VAX-31 數據。所以它與 VAX-24 的差距並不大。因此，一旦我們收到 VAX-24 數據，我們將能夠更好地判斷 31 價的有效空間有多大。

Recall, in this 24-valent study, we do have that mixed dose cohort, which gives us a leading indication of how much the incremental protein carrier will affect immune responses. For the studies to-date, we haven't seen much of an effect of the incremental protein carrier, at least not nearly to the extent the previous technologies have faced.

回想一下，在這項 24 價研究中，我們確實有混合劑量隊列，這為我們提供了增量蛋白質載體對免疫反應影響程度的領先跡象。就迄今為止的研究而言，我們還沒有看到增量蛋白質載體的太大影響，至少沒有達到先前的技術所面臨的程度。

So yes, we're going to have, hopefully, a decision to make. I think we're going to be in a good position with either VAX-24, but arguably an even stronger position to the extent the VAX-31 data is positive. But we'll be taking all those things into consideration, Seamus, as we have that data readout over the ensuing 12 to 15 months. Your question about efficacy studies, I think you were kind of hinting at some of the macro backdrop of what's going on.

所以是的，我們希望能夠做出決定。我認為，無論是 VAX-24 還是 VAX-24，我們都會處於有利地位，但如果 VAX-31 資料呈現積極態勢，我們的地位甚至會更加穩固。但是，西莫斯，我們會把所有這些因素都考慮進去，因為我們有未來 12 到 15 個月的數據讀數。您關於功效研究的問題，我認為您暗示了正在發生的一些宏觀背景。

There's no question that pneumococcal conjugate vaccines have been studied with the utmost integrity, clarity with placebo-controlled studies, certainly at their outset when they were developed initially in infants. So there is absolutely no question of the clear and present danger of pneumococcal bacteria and the effect of these vaccines that prevent 90% to 95% of infections.

毫無疑問，肺炎鏈球菌結合疫苗在嬰兒身上最初研發時就已經透過安慰劑對照研究進行了極為完整且清晰的研究。因此，對於肺炎球菌的明顯危險以及可預防 90% 至 95% 感染的疫苗的效果，絕對沒有任何疑問。

So I think the way you kind of phrased it was, is there an opportunity there for us to distinguish ourselves with an efficacy study that's manageable. And I think Jim has something in mind as a potentiality.

所以我認為，按照您的說法，我們是否有機會透過可管理的功效研究來脫穎而出。我認為吉姆心中已經有了某種可能性。

Yes. No, I'd say up to 80% of infants get a case of otitis media, almost 50% get multiple cases. So this is a very common ubiquitous type of manifestation. And the majority of causes, the main driver is Strep Pneumonia. Now for the current PCV20, they prevent roughly mid-30s to high -- to low 40 percentile in terms of overall serotype coverage.

是的。不，我認為多達 80% 的嬰兒會罹患中耳炎，幾乎 50% 的嬰兒會罹患多發性中耳炎。這是一種非常常見且普遍存在的表現類型。大多數病因的主要驅動因素是鏈球菌性肺炎。對於目前的 PCV20，就整體血清型覆蓋率而言，它們可以預防大約 30% 到 40% 左右的病毒。

But with our 31, we're in the mid-80s to low 90s. And so we think that even with a comparative study, we will have enough cases with that type of incidence and that type of improvement in coverage to be able to do a study of otitis media and actually determine the efficacy.

但對於我們的 31 人來說，我們的水平已經處於 85 到 90 左右了。因此我們認為，即使透過比較研究，我們也會有足夠的具有這種發病率和這種覆蓋率改善的病例，從而能夠對中耳炎進行研究並真正確定其療效。

As you said, it's going to take longer than an immunogenicity study in safety. So most likely, we would see that come in after the approval, but we do plan on exploring the possibility of doing an efficacy study with otitis media for our 31-valent.

正如您所說，這將比安全性免疫原性研究花費更長的時間。因此，最有可能的是，我們會在獲得批准後看到這一點，但我們確實計劃探索對我們的 31 價中耳炎進行功效研究的可能性。

Jason Gerberry, Bank of America.

美國銀行的 Jason Gerberry。

Hi, good afternoon. This is Dina on for Jason. Congrats on all the progress this year. We just had a couple on the VAX-24 infant study. First, we would like to get your view on if -- and/or how this initial primary dose series data set will provide read across to derisking VAX-31 in the infant population? And can you just remind us if you have the ability to tweak VAX-24 doses in certain serotypes depending on what's seen in the Phase II?

嗨，下午好。這是 Dina 為 Jason 表演的。恭喜你今年的所有進步。我們剛剛對 VAX-24 嬰兒進行了研究。首先，我們想聽聽您的意見，這個初始主要劑量系列資料集是否以及/或如何為降低嬰兒群體中 VAX-31 的風險提供參考？您能否提醒我們，您是否有能力根據第二階段的觀察結果調整某些血清型的 VAX-24 劑量？

And if that would be a consideration for Phase III dose selection? And then I just have a quick follow-up on the regulatory front. What specific measures would RFK have to take in order to actually change the PCV routine child vaccination schedule I guess, said in a different way, what are kind of the hurdles that he would have to overcome? And does he have the sole power to do so? Thanks so much.

這是否會成為 III 期劑量選擇的考慮因素？然後，我將快速跟進監管方面的問題。我想，羅伯特甘迺迪需要採取哪些具體措施才能真正改變 PCV 常規兒童疫苗接種計劃，換句話說，他需要克服哪些障礙？他是否擁有這樣做的唯一權力？非常感謝。

Yes. Thanks, Dina. So as it relates to the VAX-24 infant data reading across to VAX-31, yes, to be sure, I mean, just like we saw in adults, we were able to look at, in particular, the dose ascension from the low, middle to the mixed. And that mixed dose cohort was able to take a look at a similar amount of the protein carrier that is in our VAX-31 formulation and was definitely a leading indicator of what we thought we could expect with the VAX-31 data when it read out in adults.

是的。謝謝，黛娜。因此，就 VAX-24 嬰兒數據讀取到 VAX-31 而言，是的，可以肯定，我的意思是，就像我們在成年人身上看到的那樣，我們能夠特別觀察從低、中到混合的劑量上升。而且，這個混合劑量組能夠檢測出我們 VAX-31 配方中相似量的蛋白質載體，這絕對是我們認為在成人中讀取 VAX-31 數據時可以預期的結果的一個領先指標。

And of course, it was even better than we could have predicted from that mixed dose data. So I think that we will have a similar opportunity with this infant data to use it as a bellwether for how to think about the VAX-31 data when it does read out. So of course, what we found was with that incremental protein carrier, we really didn't see a falloff in the magnitude of immune responses when compared to Prevnar 20.

當然，它甚至比我們根據混合劑量數據預測的還要好。因此我認為，我們將有類似的機會利用這些早期數據作為在讀取 VAX-31 數據時如何思考的風向標。因此，當然，我們發現，使用增量蛋白質載體，與 Prevnar 20 相比，我們確實沒有看到免疫反應強度的下降。

So if the VAX-24 data is good, I think it will definitely only triangulate our confidence that came from the adult data for VAX-31. To your question about tweaking the doses of individual serotypes, most definitely, that will be afforded to us. We have seen a really nice consistent pattern of dose response across all three of the Phase II studies that we've run.

因此，如果 VAX-24 數據良好，我認為它肯定只會對來自 VAX-31 成人數據的信心進行三角測量。對於您提出的關於調整個別血清型劑量的問題，我們肯定會這樣做。在我們進行的所有三項 II 期研究中，我們都看到了非常好的一致劑量反應模式。

And there's a wide birth that's afforded based on the toxicology studies that are conducted. And so indeed, we will reserve the right to potentially tweak certain doses if we see response that should and could be improved. And then your third question would be related to potential changes to the immunization schedule for pneumococcal conjugate vaccines. I think it's really hard to predict what might happen.

根據所進行的毒理學研究，可以得出廣泛的結論。因此，如果我們發現應該或可以改善的反應，我們將保留調整某些劑量的權利。然後，您的第三個問題與肺炎鏈球菌結合疫苗免疫接種計劃的潛在變化有關。我認為很難預測會發生什麼。

There's been no discussion of pneumococcal conjugate vaccines to-date in any forum. So I don't think there's anything to go on to make us think that there would ever be an effort to reduce the schedule associated with pneumococcal conjugate vaccines. This is not some distant memory of a pathogen.

迄今為止，任何論壇上都沒有討論過肺炎鏈球菌結合疫苗。因此，我認為沒有任何理由讓我們認為需要努力減少與肺炎鏈球菌結合疫苗相關的接種時間表。這並不是某種病原體的遙遠記憶。

This is a pathogen that is routinely circulating and inhabiting the upper respiratory tract of a substantial portion of our population. And the moment you pull back a dose or pull back rates of immunization with pneumococcal conjugate vaccines, more kids and more adults will get sick and more adults and more infants will die. There's no question of that. So I don't think there's really a thesis to suggest that there would be a path or an impetus to do something like that.

這是一種經常傳播並寄生於我們相當一部分人口的上呼吸道中的病原體。一旦減少肺炎鏈球菌結合疫苗的劑量或免疫率，就會有更多的兒童和成年人患病，也會有更多的成年人和嬰兒死亡。毫無疑問。因此，我認為實際上沒有論點表明存在做這樣的事情的途徑或動力。

And may I just add to Grant's comments. I mean the -- the environment is right, as I said, 25 years of vaccination of infants, 15 years of adults, the health and economic benefits are very clear, right? The current system is incredibly complex, really an institution involving multiple, multiple stakeholders.

我可以補充一下格蘭特的評論嗎？我的意思是——環境是正確的，正如我所說，嬰兒接種疫苗 25 年，成人接種疫苗 15 年，健康和經濟效益非常明顯，對嗎？目前的系統極為複雜，實際上是一個涉及多個利害關係人的機構。

And I would also maybe say, and I can perhaps to Salim's earlier question, refer us all to the comments that Senator Cassidy made in connection with his decision to support the nomination of RFK Jr. to the Senate, speaking directly to a number of commitments that he obtained from both Kennedy and the administration, including kind of maintaining the ACIP that is one of the important bodies in terms of the recommendation of immunization schedules among other commitments kind of all geared toward kind of the status quo as it exists with respect to vaccination.

我可能還會說，或許我可以回答薩利姆之前的問題，請大家參考卡西迪參議員在支持提名羅伯特·肯尼迪進入參議院的決定中所發表的評論，他直接談到了肯尼迪和政府給予他的一些承諾，包括維持美國預防接種計劃委員會 (ACIP)，該委員會是推薦免疫接種計劃方面的重要機構之一，以及其他旨在維持疫苗接種現狀的承諾。

And there are other bodies as well at the AAP, American Academy of Pediatrics that itself put out a statement a while back that plays an important role in the immunization of our infants as well.

美國兒科學會（AAP）等其他機構不久前也發表聲明，表示在嬰兒免疫接種方面也扮演重要角色。

Tom Shrader, BTIG.

BTIG 的湯姆·施拉德 (Tom Shrader)。

Good afternoon. Thank you for answering so many of my questions. With all the noise about ACIP, I wanted to squeeze in one more about current medical practice. Adults with risk factors have gotten PCVs at 50 for a while now. Is it standard practice to boost them at 65? And I guess really the question is, if everyone is getting them at 50 now, is it kind of the expectation they'll get boosted at 65? Or do you really need ACIP to hardwire that? And if you have any thoughts on whether insurance will pay for that second shot, it would be great as well.

午安.感謝您回答了我這麼多的問題。由於 ACIP 的討論如此熱烈，所以我想再擠出一點時間來談論當前的醫療實踐。有風險因素的成年人在 50 歲時接種 PCV 已經有一段時間了。在 65 歲時提高生育率是標準做法嗎？我想真正的問題是，如果現在每個人都在 50 歲時獲得這些福利，那麼是否預計他們會在 65 歲時獲得提升？或者你真的需要 ACIP 來硬連線它嗎？如果您對保險是否會支付第二次注射的費用有任何想法，那就太好了。

Thank you.

謝謝。

Yes. Tom, thank you for the question. Maybe Jim and I can tag team this one. I mean, going back prior to the pneumococcal conjugate vaccines being approved in adults 15 years ago and only up until recently was there a two-vaccine schedule. So 15 years ago, there was only the polysaccharide-only vaccine and then Prevnar 13 got approved.

是的。湯姆，謝謝你的提問。也許我和吉姆可以組隊一起做這件事。我的意思是，早在 15 年前肺炎球菌結合疫苗獲得成人批准之前，直到最近才有了兩種疫苗的接種計劃。15 年前，只有多醣體疫苗，後來 Prevnar 13 獲得批准。

And until Prevnar 20 was approved, Pneumovax was also recommended on top of the pneumococcal conjugate vaccine. And in the case of the polysaccharide-only vaccine, that was administered by recommendation every five years. So multiple vaccine doses have been a consistent feature of the adult vaccination range.

在 Prevnar 20 獲得批准之前，除了肺炎鏈球菌結合疫苗外，還建議使用 Pneumovax。對於僅含多醣體的疫苗，建議每五年接種一次。因此，多劑量疫苗接種一直是成人疫苗接種範圍的一貫特徵。

And at the last ACIP meeting, there was quite a bit of discussion around how long should you wait for a second vaccination once we start giving the routine universal vaccination at age 50. To your point, Tom, people with certain health conditions have been getting vaccinated in that range for some time.

在上次 ACIP 會議上，我們圍繞 50 歲開始進行常規全民接種疫苗後，應該等待多長時間才能進行第二次接種進行了大量的討論。正如你所說，湯姆，患有某些健康狀況的人已經接種該範圍內的疫苗一段時間了。

And there was a real recognition that another vaccination dose should come in when they turn 65, but there was reticence on the part of the ACIP to go there just yet. And what they were really looking for was the newer, higher valent vaccines to come out. And then those could be the second vaccination when people turn 65.

人們確實意識到，當人們年滿 65 歲時應該接種另一劑疫苗，但 ACIP 方面目前還不願意這樣做。他們真正尋求的是更新、更有效率價的疫苗。當人們年滿 65 歲時，這可能是第二次接種疫苗。

And it was gratifying to see that we were the vaccines that they were referencing, both VAX-24 and VAX-31. So yes, I think that is where the future is headed. It hasn't been codified. But to your point, if an individual goes in and they're within the right age range, it's likely that they'll get the vaccine if they ask for it. I mean that's just kind of how we're conditioned.

令人欣慰的是，我們研發的正是他們所提到的疫苗，VAX-24 和 VAX-31。是的，我認為這就是未來的發展方向。它還沒有被編纂成法典。但就你的觀點而言，如果一個人去接種疫苗並且年齡在合適的範圍內，那麼他們很可能會接種疫苗（如果他們提出要求的話）。我的意思是，這只是我們被培養出來的習慣。

And there haven't been any controls on reimbursement for multiple doses to-date that I have seen.

據我所知，迄今為止還沒有對多劑量藥物的報銷做出任何控制。

And these vaccines have such a great return on investment. Every dollar you spend on vaccines return depending on the class, $7 to $11 in savings to the health care system. And that's why given their safety profile, given the efficiency when people go in and ask their pharmacists for a vaccine, more often than not, they'll get it even if it's a second vaccine that they had gotten to one previously in their history.

這些疫苗的投資報酬率非常高。您花在疫苗上的每一美元都會為醫療保健系統節省 7 至 11 美元（取決於疫苗種類）。這就是為什麼考慮到疫苗的安全性和效率，當人們去藥劑師那裡購買疫苗時，他們往往都會接種，即使這是他們以前接種過的第二種疫苗。

So yes, I think you're kind of setting things up. Not everything has been totally solidified, but the ground is fertile for what should be the case, which is people getting multiple vaccinations over the course of their lives, particularly as their immune systems begin to wane as they get into their 60s and 70s.

是的，我認為你正在做一些安排。雖然並非所有事情都已完全確定，但為應該實現的目標奠定了基礎，即人們在一生中接種多次疫苗，特別是當他們進入 60 多歲和 70 多歲時，免疫系統開始減弱。

Joseph Stringer, Needham & Company.

約瑟夫·斯特林格，Needham & Company。

Hi, thanks for taking our questions. We assume the eventual approval of either VAX-24 or VAX-31, what's your current thinking on the likelihood that ACIP would not grant a preferred recommendation? I realize this would sort of go against precedent, but could you give your updated thoughts on the puts and takes on this hypothetical scenario? And -- has your outlook on this changed at all with the new administration?

您好，感謝您回答我們的問題。我們假設 VAX-24 或 VAX-31 最終獲得批准，您目前認為 ACIP 不會授予優先推薦的可能性如何？我意識到這有點違背先例，但您能否就這假設情境的利弊發表最新看法？而且—隨著新政府的上台，您對此的看法有什麼改變嗎？

Yes. Joe, thanks for the question. Yes, I mean we've got -- VAX-31 will be first up. As we look ahead, we've got to obviously complete the Phase III studies. But given the strength of the treatment effect in Phase II, we're extremely confident heading into the Phase III experiment.

是的。喬，謝謝你的提問。是的，我的意思是我們已經有了——VAX-31 將會是第一個。展望未來，我們顯然必須完成第三階段的研究。但考慮到第二階段治療效果的強度，我們對進入第三階段實驗非常有信心。

Once we have that package together and we have to get all of our BLA together, et cetera, et cetera. But looking ahead to a potential ACIP review, we have a product that has the makings of the most compelling profile that they would have reviewed to-date. And even the last occasion where an adult pneumococcal conjugate vaccine was debated, I think there were expectations that, that profile could have warranted a preferred recommendation, but for the fact that while it had improved coverage, it did not cover historically circulating strains, some of which were actively circulating in the moment.

一旦我們有了這個包裹，我們就必須把所有的 BLA 都放在一起，等等。但展望潛在的 ACIP 審查，我們的產品具有他們迄今為止審查過的最引人注目的品質。甚至在上次討論成人肺炎球菌結合疫苗時，我認為人們曾期望該疫苗可以獲得優先推薦，但事實是，雖然該疫苗的覆蓋率有所提高，但它並未覆蓋歷史上流行的菌株，其中一些菌株目前正在活躍傳播。

And so for us, we have a product profile, at least based on what we've seen to-date that has even higher coverage than that particular vaccine while covering the historically circulating strains and improving immune responses to boot, which are multiple advantages relative to what anyone else has ever seen.

因此，對我們來說，至少根據我們迄今為止所見，我們的產品概況比特定疫苗具有更高的覆蓋率，同時涵蓋了歷史上傳播的菌株並改善了免疫反應，這是相對於其他人所見的多重優勢。

And we have seen preferred recommendations granted in the adult setting. And it gives us the kind of confidence that it's certainly something that we can plan for. It's not a guarantee, but something that we can plan for. In the infant setting, the last conversation was when Prevnar 20 was approved and debated.

我們已經看到在成人環境中獲得了優先推薦。這讓我們有信心，這肯定是我們可以規劃的。這不是一個保證，而是我們可以計劃的事情。在嬰兒環境中，最後一次對話是批准和討論Prevnar 20時。

And really, the coverage there based on the dialogue they had was enough to warrant a preferred recommendation, but they explicitly did not grant it the preferred recommendation because of the diminished immune responses that were evident, which is the reason why as we think about our 24-valent and 31-valent moving forward, it gives us a lot of confidence that VAX-24, which is ahead, truly does have a differentiated superior profile in that if we can see anything similar to the adult results where we're not only conferring broader coverage with additional conjugates, but also potentially higher immune responses, that would have been precisely what they were looking for when they last considered a preferred recommendation.

實際上，根據他們之間的對話，覆蓋範圍足以保證優先推薦，但他們明確沒有授予它優先推薦，因為免疫反應明顯減弱，這就是為什麼當我們考慮 24 價和 31 價疫苗的發展時，它給了我們很大的信心，領先的 VAX-24確實具有差異化的優勢，如果我們能看到與成人結果相似的任何結果，即我們不僅通過額外的結合物賦予了更廣泛的覆蓋範圍，而且還可能具有更高的免疫反應，這正是他們上次考慮優先推薦時所尋找的。

And then I think as it relates to what will happen in the future, we're a ways away from that ACIP conversation, that ACIP composition, et cetera. So I think it's premature to suggest anything other than the basis for which these decisions have been made historically, which is based on the merits of the vaccine for which they're considering relative to the vaccines that are the standard of care up to that point and to what extent the newer vaccine can provide better protection and better return on investment for this country.

然後我認為，就未來將要發生的事情而言，我們距離 ACIP 對話、ACIP 組成等等還有一段距離。因此，我認為現在提出任何建議都為時過早，除了這些決定的歷史依據之外，這些決定是基於他們正在考慮的疫苗相對於當時的標準疫苗的優點，以及新疫苗在多大程度上可以為這個國家提供更好的保護和更好的投資回報。

Ladies and gentlemen, that will conclude today's question-and-answer period and also concludes today's Vaxcyte fourth quarter and full-year 2024 earnings call. Please disconnect your line at this time and have a wonderful day. Goodbye.

女士們，先生們，今天的問答環節到此結束，今天的 Vaxcyte 第四季度和 2024 年全年收益電話會議也到此結束。請此時斷開您的線路並祝您有美好的一天。再見。