Invivyd, Inc. (IVVD) 2025 Q4 法說會逐字稿

Good day. Thank you for standing by. Welcome to the Invivyd fourth-quarter 2025 earnings conference call. (Operator Instructions) Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Katie Falzone, Senior Vice President of Finance. Please go ahead.

大家好。感謝各位稍候。歡迎參加 Invivyd 2025 年第四季財報電話會議。(接線員指示) 請注意，今天的會議將被錄音。現在我想把會議交給今天的講者——財務資深副總裁 Katie Falzone。請開始。

Thank you, operator. A short while ago, we issued a press release announcing our Q4 2025 financial results and recent business highlights. That press release and the slides that we are being used today on today's webcast can be found in the Investors section of the Invivyd website under the Press Release and Events and Presentations sections, respectively.

謝謝接線員。稍早我們已發布新聞稿，公布 2025 年第四季財務結果與近期業務重點。該新聞稿以及我們今天網路直播所使用的簡報投影片，分別可在 Invivyd 官網「投資人」專區中的「新聞稿」以及「活動與簡報」欄位找到。

Today's discussion will be led by Marc Elia, Chairman of Invivyd Board of Directors. He is joined by Tim Lee, Chief Commercial Officer, Bill Duke, Chief Financial Officer, and Dr. Robbie Allen, Chief Scientific Officer. During today's discussion, we will be making forward-looking statements concerning, among other things, our corporate and commercial strategy, our research and development activities, our regulatory plans, certain financial expectations, our future prospects, and other statements that are not historical facts.

今天的討論將由 Invivyd 董事會主席 Marc Elia 主持。與會者包括商務長 Tim Lee、財務長 Bill Duke，以及首席科學長 Robbie Allen 博士。在今天的討論中，我們將就（其中包括）公司與商業策略、研發活動、法規/監管計畫、若干財務預期、未來展望，以及其他非歷史事實之陳述，作出前瞻性聲明。

These forward-looking statements are covered within the meaning of the Private Securities Litigation Reform Act and are subject to various risks, assumptions and uncertainties that may change over time and cause our actual results to differ materially from those expressed or implied today. These forward-looking statements speak only as of the date of this call. Invivyd assumes no duty to update such statements. Additional information on the risk factors that could affect Invivyd business can be found in our filings made with the US Securities and Exchange Commission, including our most recent Form 10-K, which are also available on our website.

這些前瞻性聲明屬於《私人證券訴訟改革法》所界定之範圍，並受多項風險、假設與不確定性影響；這些因素可能隨時間改變，並導致我們的實際結果與今日所表達或暗示者出現重大差異。這些前瞻性聲明僅截至本次電話會議當日有效。Invivyd 不承擔更新此等聲明之義務。有關可能影響 Invivyd 業務之風險因素的更多資訊，請參閱我們向美國證券交易委員會（SEC）提交的文件（包括最新的 Form 10-K），亦可於我們網站查閱。

I will now turn the call over to Marc.

現在我把電話交給 Marc。

Thank you, Katie, good morning, everyone. I'll make a few quick remarks by way of executive summary, then we'll discuss our clinical progress.

謝謝你，Katie，各位早安。我先以執行摘要的方式做幾點簡短說明，接著我們將討論臨床進展。

Of note, this morning you may have seen that we have brought an esteemed physician scientist, Michael Mina, into the Invivyd fold to serve as our Chief Medical Officer. While Michael is unable to join our call this morning, I'm sure many of you will enjoy hearing from him going forward.

值得一提的是，今天早上各位可能已看到，我們延攬備受尊敬的醫師科學家 Michael Mina 加入 Invivyd，擔任首席醫療長。雖然 Michael 今天早上無法參與電話會議，但我相信未來各位會很期待聽到他的分享。

After the clinical discussion, Tim Lee, our Chief Commercial Officer, will review our work with PEMGARDA and some of our pre-commercial preparation for VYD2311. Bill Duke, our Chief Financial Officer, will touch on our financial results for 4Q, then we will be happy to take your questions. Now on to the highlights.

臨床討論之後，我們的商務長 Tim Lee 將回顧我們在 PEMGARDA 的工作，以及針對 VYD2311 的部分上市前準備。我們的財務長 Bill Duke 將說明第四季財務結果，之後我們很樂意回答各位的問題。接下來進入重點摘要。

Our REVOLUTION clinical program is well underway, with the aim of providing Americans with an option for what we believe is needed protection from symptomatic COVID disease. We know investors have many questions about our progress, and we will provide as much detail today as we can.

我們的 REVOLUTION 臨床計畫進展順利，目標是為美國民眾提供一個選項，以取得我們認為所需、可預防有症狀 COVID 疾病的保護。我們知道投資人對我們的進度有許多疑問，今天我們將盡可能提供更多細節。

Our commercial work with PEMGARDA continues, and we were pleased to demonstrate growth in the fourth quarter. Our commercial activities are establishing an attractive basis for broader commercialization of VYD2311, if approved, by demonstrating the power and durability potential of Invivyd monoclonal antibodies.

我們與 PEMGARDA 相關的商業工作持續推進，且很高興在第四季展現成長。我們的商業活動透過展現 Invivyd 單株抗體的效力與潛在持久性，正在為 VYD2311（若獲核准）的更廣泛商業化建立具吸引力的基礎。

We are continuing to build awareness and understanding of our work with monoclonal antibodies among HCPs, professional societies, vulnerable populations, and government public health entities. We believe that the ongoing American experience with COVID vaccination has left an extraordinary high medical and economic value opportunity to advance standard of care via monoclonal antibody prophylaxis.

我們持續在醫療照護專業人員（HCP）、專業學會、脆弱族群以及政府公共衛生機構之間，建立對我們單株抗體工作的認知與理解。我們相信，美國持續的 COVID 疫苗接種經驗，留下了一個極高的醫療與經濟價值機會，可透過單株抗體預防性用藥來推進照護標準。

In the pipeline, we are excited to begin clinical exploration of our antibodies in long COVID and post-vaccination syndrome, as disclosed earlier this quarter. We are very interested that the Advisory Committee on Immunization Practices, or ACIP, a group which advises the US Centers for Disease Control, have recently announced that they are having a full discussion on both topics. The ACIP meeting is currently scheduled for March 18th and 19th. We will be watching with interest.

在產品線方面，如同本季稍早所揭露，我們很期待開始在長新冠（long COVID）與疫苗接種後症候群（post-vaccination syndrome）中，進行我們抗體的臨床探索。我們也非常關注免疫實務諮詢委員會（Advisory Committee on Immunization Practices，ACIP）——一個為美國疾病管制與預防中心（CDC）提供建議的團體——近期宣布將就這兩個議題進行完整討論。ACIP 會議目前排定於 3 月 18 日與 19 日舉行。我們將持續關注。

Our collaboration with key academic thought leaders in this space, the SPEAR Study Group, has yielded a clinical trial design we are moving with all haste to action in light of the substantial unmet need for millions of Americans suffering from long COVID and vaccine injury. In the fourth quarter, we were pleased to share our identification of a highly potent, potentially best-in-class RSV antibody.

我們與此領域關鍵學術意見領袖（SPEAR 研究小組）的合作，已產出一項臨床試驗設計；鑑於數以百萬計美國人受長新冠與疫苗傷害所苦、未被滿足的需求龐大，我們正以最快速度推動落地執行。在第四季，我們也很高興分享我們辨識出一款效力極高、可能同級最佳（best-in-class）的 RSV 抗體。

As you may know, there are today two RSV antibodies approved and recommended for the prevention of RSV in certain neonatal and pediatric populations, and we believe the properties of our antibody are highly competitive with standard of care. As we advance our work across multiple infectious diseases, you may notice a special interest in pediatrics. RSV, COVID, and indeed other viruses exert substantial medical burden on both the elderly and the very young, as well as immunocompromised persons.

各位可能知道，目前已有兩款 RSV 抗體獲核准並被建議用於特定新生兒與兒科族群的 RSV 預防；我們相信我們抗體的特性在與現行照護標準相比時具高度競爭力。隨著我們在多種傳染病上推進工作，各位可能會注意到我們對兒科領域有特別的關注。RSV、COVID，乃至其他病毒，對高齡者與年幼族群以及免疫功能低下者，都造成沉重的醫療負擔。

Finally, as previously guided, we expect to update the street on our measles program in the first half of this year. In light of the substantial and rapidly growing burden of disease, we are excited to share our progress with you, as well as describing what we see as the potential medical value of such an antibody, which we hope can be both first and best in class. Slide five.

最後，如先前所指引，我們預期將在今年上半年向市場更新我們的麻疹計畫。鑑於疾病負擔顯著且快速攀升，我們很期待與各位分享進展，並說明我們所見此類抗體的潛在醫療價值；我們希望它能同時成為同類首創（first-in-class）且同級最佳（best-in-class）。第 5 張投影片。

Moving on to our clinical update. On slide 6, we know that there are investors who are new to the Invivyd story, and so we'd like to review quickly the medical and scientific background for our work with VYD2311, which hopefully will add context to the updates we provided on the DECLARATION study in our press release this morning.

接著進入臨床更新。在第 6 張投影片，我們知道有些投資人是第一次接觸 Invivyd 的故事，因此我們想快速回顧 VYD2311 相關工作的醫學與科學背景，希望能為我們今天早上新聞稿中提供的 DECLARATION 研究更新補充脈絡。

First, it's important to remember that SARS-CoV-2 has been an extraordinary, unwelcome, and ongoing medical burden on the human species. As an ACE2 receptor accessing Betacoronavirus adapted for high human virulence and transmissibility, it has exerted medical toll in two distinct phases. In the initial pandemic phase, the virus swiftly moved through the human population, exerting substantial morbidity and mortality, especially among vulnerable populations such as the elderly and people with relevant comorbidities such as pre-existing cardiovascular and renal disease.

首先，重要的是要記住，SARS-CoV-2 對人類而言一直是極其沉重、令人不樂見且仍在持續的醫療負擔。作為一種透過 ACE2 受體進入細胞、並已適應為對人類具高度毒力與傳播力的 β 冠狀病毒，它在兩個不同階段造成了醫療衝擊。在最初的大流行階段，病毒迅速在族群中傳播，造成顯著的發病率與死亡率，尤其是在高風險族群，例如高齡者，以及具有相關共病者（如既有心血管與腎臟疾病）。

After vaccination and mounting seropositivity, we see a predictably less violent mortality but still extraordinary medical burden from this virus, generally in the same populations. As a vascular prothrombotic immunomodulatory virus that circulates pervasively, we now see accelerated human aging and broad health effects in Americans from acute infection with attendant risks through the substantial growth in long COVID prevalence. Even American economic data collected by the Fed appears to show an unwelcome, impressive growth in American disability since COVID entered our population. We must be less tolerant of this burden.

在疫苗接種與血清陽性率上升之後，我們看到死亡率如預期般較不劇烈，但此病毒仍帶來非同尋常的醫療負擔，且通常仍集中在相同族群。作為一種具血管性、促血栓、免疫調節特性的病毒，且廣泛循環存在，我們如今看到美國人在急性感染後出現加速老化與廣泛健康影響，並伴隨長新冠盛行率大幅上升所帶來的相關風險。甚至聯準會（Fed）蒐集的美國經濟數據似乎也顯示，自 COVID 進入我們族群以來，美國的失能（disability）出現令人不樂見且顯著的成長。我們必須對這種負擔更不容忍。

Second, given all of the relevant sociopolitical and medical aspects of this controversial field, we must touch on the evidentiary and regulatory history we have in COVID prophylaxis. The mRNA-based COVID vaccines were each formally studied in a single placebo-controlled clinical trial in the second half of 2020.

第二，鑑於這個具爭議領域所有相關的社會政治與醫療面向，我們必須談及我們在 COVID 預防方面所累積的證據與監管歷史。以 mRNA 為基礎的 COVID 疫苗各自於 2020 年下半年在一項安慰劑對照臨床試驗中接受正式研究。

These studies assessed vaccine safety and efficacy versus placebo in a seronegative American population against highly immunologically responsive Wuhan-derivative virus variants for about seven to eight weeks before unblinding. These studies demonstrated high short-term protection and short-term safety. However, these original data sets also reflect the last opportunity we had as a species to assess absolute safety in randomized placebo-controlled trials.

這些研究在一個血清陰性的美國族群中，針對免疫反應性很高的武漢衍生病毒變異株，在揭盲前約七到八週期間，評估疫苗相較於安慰劑的安全性與有效性。這些研究顯示短期保護力高且短期安全性良好。然而，這些原始資料集也反映出：那是我們這個物種最後一次能在隨機安慰劑對照試驗中評估絕對安全性的機會。

Given the broad vaccine mandates and rapid virus spread, we as a human species are now all routinely exposed to SARS-CoV-2 and its spike protein, which we see as a type of toxin, and absent a new medical option, we as a species have no real opportunity to avoid exposure to spike protein chronically going forward. Shortly after those original vaccine studies and vaccine rollout, our entire species became immunologically educated or seropositive, either through the original campaign or circulating virus, all while undergoing excess morbidity and mortality.

在廣泛的疫苗強制措施與病毒快速傳播之下，我們人類如今都例行性地暴露於 SARS-CoV-2 及其棘蛋白；我們將其視為一種毒素。而在缺乏新的醫療選項下，作為一個物種，我們未來基本上沒有真正的機會避免長期、慢性地暴露於棘蛋白。在最初的疫苗研究與疫苗推行後不久，我們整個物種不論是透過最初的接種行動或透過流行病毒，都在免疫學上受到教育或轉為血清陽性，同時也經歷了超額的發病與死亡。

Omicron phylogeny virus arose quickly following as an evolutionary acquisition of population immunity. Omicron viruses are defined by immune evasiveness or the functional avoidance of human immunologic pressure, whether vaccine-induced or natural.

Omicron 系譜病毒在族群免疫作為一種演化獲得後迅速出現。Omicron 病毒的特徵在於免疫逃逸性，或功能性地避開人類免疫壓力，不論該壓力是疫苗誘發或自然感染所致。

One major consequence of Omicron virus was a natural, predictable, apparent reduction in COVID vaccine efficacy, which has been reliably estimated by epidemiologists at CDC over the past year and was directly measurable in diminished vaccine titers when vaccine manufacturers updated COVID vaccine compositions from Wuhan variant virus to Omicron BA.4/5 virus.

Omicron 病毒的一個重大後果，是 COVID 疫苗效力出現自然、可預期且明顯的下降；過去一年 CDC 的流行病學家已可靠地估算此一現象，且當疫苗製造商將 COVID 疫苗成分由武漢株更新為 Omicron BA.4/5 病毒時，這也可直接從疫苗抗體效價下降中量測到。

These analyses can be seen in the relevant vaccine labels, we see them as predictive of diminished efficacy. COVID vaccine boosts have undergone five structural updates since Wuhan virus vaccines just on the basis of immunologic comparison. Ongoing new placebo-controlled vaccine studies should provide us all with more insight into these issues in the coming quarters.

這些分析可在相關疫苗標籤中看到；我們認為它們可用來預測效力下降。僅基於免疫學比較，COVID 疫苗追加劑自武漢株疫苗以來已進行五次結構性更新。持續進行的新安慰劑對照疫苗研究，應能在未來幾個季度為我們所有人提供更多對這些議題的洞見。

By contrast, Invivyd is now conducting its third randomized placebo-controlled trial for a COVID monoclonal antibody in five years. Our antibodies change one to the next, rather like the vaccines, to make allowance for virus evolution, although we hope to stay ahead of virus variation rather than chasing it from behind.

相較之下，Invivyd 現在在五年內針對一款 COVID 單株抗體進行第三項隨機安慰劑對照試驗。我們的抗體會一代接一代地改變，與疫苗相當類似，以因應病毒演化；不過我們希望能領先病毒變異，而不是在後面追趕。

On a percentage basis, our antibodies change by about the same tiny amount as vaccine antigens, but in contrast to COVID vaccines, we see our antibodies as a much more natural, welcome approach to prophylaxis than serial exposure to spike protein in vaccine form.

以百分比來看，我們的抗體變動幅度約與疫苗抗原同樣微小；但與 COVID 疫苗不同的是，我們將抗體視為一種更自然、也更受歡迎的預防方式，而不是以疫苗形式反覆暴露於棘蛋白。

To us, given the apparent short duration of vaccine-induced protection and the potential risks of administering spike protein in either mRNA or protein form, it is natural to now move to supplemental immune support via monoclonal antibody to exert protection.

在我們看來，鑑於疫苗誘發保護的持續時間似乎很短，以及以 mRNA 或蛋白形式給予棘蛋白可能存在的風險，現在轉向以單株抗體提供補充性的免疫支持以發揮保護作用，是很自然的選擇。

From an evidentiary and regulatory point of view, our Invivyd antibodies have undergone more extensive placebo-controlled characterization than the COVID vaccines, including now multiple placebo-controlled clinical trials and, in our recent CANOPY study, long-term characterization of pemivibart in a modern seropositive population and against Omicron virus variants.

從證據與監管角度來看，我們的 Invivyd 抗體已接受比 COVID 疫苗更廣泛的安慰劑對照特性描述；其中包括目前多項安慰劑對照臨床試驗，以及在我們近期的 CANOPY 研究中，於現代血清陽性族群、並針對 Omicron 病毒變異株，對 pemivibart 進行長期特性描述。

That brings us to our latest antibody, VYD2311, designed as an alternative to COVID vaccination. VYD2311 is much more potent than pemivibart in vitro and has a longer measured half-life, properties which we believe may combine to deliver equivalent protection to PEMGARDA but in a much more scalable and convenient intramuscular form.

這就帶到我們最新的抗體 VYD2311，其設計目標是作為 COVID 疫苗接種的替代方案。VYD2311 在體外的效力遠高於 pemivibart，且量測到的半衰期更長；我們相信這些特性可能結合起來，提供與 PEMGARDA 相當的保護，但以更可擴展且更便利的肌肉注射形式給藥。

You can see on slide 8 a reminder of the initial pieces of the REVOLUTION clinical program. The DECLARATION study is a triple-blind randomized clinical trial, once again evaluating the safety of VYD2311 and its ability to reduce the risk of symptomatic disease versus placebo.

您可以在投影片 8 看到 REVOLUTION 臨床計畫初始組成部分的提醒。DECLARATION 研究是一項三盲隨機臨床試驗，再次評估 VYD2311 的安全性，以及其相較於安慰劑降低有症狀疾病風險的能力。

Our target enrollment for DECLARATION is approximately 1,770 human subjects randomized one-to-one-to-one in two active arms and one placebo arm. We were recently notified that the DECLARATION clinical trial has reached target enrollment and indeed, as is normal in these situations, may modestly over-enroll as sites are permissioned to complete any ongoing screening and enrollment before closing.

DECLARATION 的目標收案約為 1,770 名受試者，以一比一比一隨機分派至兩個有效治療組與一個安慰劑組。我們近期收到通知，DECLARATION 臨床試驗已達到目標收案；而且如同此類情況的常態，當各研究中心獲准在關閉前完成任何進行中的篩選與收案時，可能會略為超收。

Of note, recently the DECLARATION Independent Data Monitoring Committee, or IDMC, conducted a pre-specified review of unblinded safety and tolerability data associated with initial experience of DECLARATION subjects. While the IDMC is completely separate from Invivyd, we are pleased to relay their written communication to us following that review, which included three recommendations.

值得注意的是，近期 DECLARATION 獨立資料監測委員會（IDMC）依預先規劃，對 DECLARATION 受試者初期經驗所累積的未揭盲安全性與耐受性資料進行審查。雖然 IDMC 與 Invivyd 完全獨立，我們很高興轉述他們在該次審查後以書面提供給我們的溝通內容，其中包含三項建議。

First, that pregnant and breastfeeding women may now enroll in the study. Second, that women of childbearing age enrolled in the study are no longer required to use contraception. Third, that pre-specified safety visits at days eight, 38, and 68 post-dosing are no longer required. Finally, DECLARATION is a study designed to assess the performance of VYD2311 in lowering the risk of symptomatic PCR-positive COVID-19 versus placebo.

第一，孕婦與哺乳期婦女現在可以納入研究。第二，參與研究的育齡女性不再被要求使用避孕措施。第三，給藥後第 8、38 與 68 天的預先規劃安全性回診不再需要。最後，DECLARATION 是一項旨在評估 VYD2311 相較於安慰劑，在降低有症狀且 PCR 陽性之 COVID-19 風險方面表現的研究。

In every infectious disease prophylaxis study, a sponsor like us faces an unknown so-called attack rate, or the rate of infection observed in the study to power our efficacy assessments. Because monoclonal antibody technology in COVID has typically involved a very high efficacy hazard ratio, or VE. Traditionally, it has not taken more than a high single-digit or low double-digit number of events in a study to generate statistical significance.

在每一項傳染病預防研究中，像我們這樣的主辦方都會面臨一個未知的所謂攻擊率（attack rate），也就是研究中觀察到的感染率，用以支持我們的有效性評估。因為 COVID 的單株抗體技術通常具有非常高的有效性風險比，或疫苗效力（VE）。傳統上，一項研究中不需要超過高個位數或低雙位數的事件數，就能產生統計顯著性。

As you may recall, alignment with the FDA on the VYD2311 clinical development pathway included recognition that in our CANOPY clinical trial of pemivibart, the placebo-controlled arm demonstrated robust exploratory efficacy with strong statistical support on the basis of nine total COVID events at three months.

您可能記得，與 FDA 就 VYD2311 臨床開發路徑達成一致時，也認可在我們針對 pemivibart 的 CANOPY 臨床試驗中，安慰劑對照組在三個月時以總計 9 起 COVID 事件為基礎，顯示出強健的探索性療效，且具有強力的統計支持。

America is in the middle of a COVID wave. We are pleased with the speed of our study recruitment. The majority of our recruitment has occurred only in the past few weeks. COVID events have begun to appear in our study. We see DECLARATION event accumulation as on track to date and on a projected basis, we anticipate suitable for robust assessment of VYD2311 effectiveness if the clinical performance of VYD2311 matches our modeling and prior experience with COVID antibodies. Of course, attack rate in the community and in our study is outside of our control and could change going forward.

美國正處於一波 COVID 流行之中。我們對研究招募的速度感到滿意。我們的大部分招募僅發生在過去幾週。研究中已開始出現 COVID 事件。我們認為截至目前 DECLARATION 的事件累積進度符合預期；並且根據推估，若 VYD2311 的臨床表現符合我們的模型與先前 COVID 抗體的經驗，我們預期其將足以對 VYD2311 的有效性進行強健評估。當然，社區與研究中的攻擊率不在我們控制之內，未來可能會有所變化。

As a result, DECLARATION includes a pre-specified upsizing algorithm to allow for additional patients in the trial should our event rate projections indicate the DECLARATION would benefit from more statistical power. This resizing feature is dependent on overall progress, and at this point, our best estimate is that such an analysis would take place in approximately April. We will make an announcement to the street about our next steps one way or the other at that time.

因此，DECLARATION 納入一項預先規劃的擴增演算法；若我們對事件率的推估顯示 DECLARATION 需要更高的統計力，該機制可允許在試驗中增加受試者人數。此一重新調整規模的功能取決於整體進度；目前我們的最佳估計是，這樣的分析將約在四月進行。屆時我們將向市場公告我們接下來的步驟，不論是否進行擴增。

However, depending on overall recruitment rates, with which we have been very pleased so far, a modest upsizing to add statistical power may not meaningfully delay our achievement of quote mid-year unquote timing guidance for DECLARATION, which we consider as 2Q or 3Q 2026. Of course, any upsizing would have some level of timing impact, but we would endeavor to stay within our original guidance boundaries.

然而，視整體招募速率而定（截至目前我們對此非常滿意），為了增加統計檢定力而進行小幅擴增樣本數，可能不會實質延後我們達成 DECLARATION「引述年中、非引述」時程指引；我們將其視為 2026 年第 2 季或第 3 季。當然，任何擴增都會在某種程度上影響時程，但我們會努力維持在原先指引的範圍內。

When we get to that point, we will be happy to provide any updated timing estimates. Irrespective of the overall number of COVID events, we are looking forward to data and believe that it may be a profound next step for our company and for infectious disease medicine if DECLARATION can demonstrate attractive VYD2311 safety, high antiviral titers, and a demonstration for the third sequential time of the vaccine-free protection that an Invivyd monoclonal antibody can provide.

等到那個時間點，我們很樂意提供任何更新的時程估計。不論整體 COVID 事件數量如何，我們都期待看到數據，並相信若 DECLARATION 能證實 VYD2311 具備良好安全性、高抗病毒滴度，且連續第三次展示 Invivyd 單株抗體可提供的「無需疫苗」保護，這可能會成為對本公司以及感染症醫療領域而言意義深遠的下一步。

With that, I'd like to turn the call over to Tim Lee to discuss our commercial update. Tim?

接下來，我想把電話會議交給 Tim Lee，請他說明我們的商業進展更新。Tim？

Thanks, Marc. It's a pleasure to update you all on our work. As we see it, more and more clinicians are turning to monoclonal antibodies. Frankly, it's common sense. Thomas Paine once wrote that common sense is often the most powerful kind of reasoning. In healthcare, when evidence accumulates and risk is clear, the logical course becomes difficult to ignore or go straightforward.

謝謝，Marc。很高興向各位更新我們的工作進展。依我們觀察，愈來愈多臨床醫師正轉向使用單株抗體。坦白說，這是常識。Thomas Paine 曾寫道，常識往往是最有力的一種推理。在醫療照護中，當證據累積且風險明確時，合乎邏輯的做法就很難被忽視，或是很難不直接採行。

It's not simple. We want to give people a choice as they seek protection against COVID. We believe that choice has significant potential because there are still millions of individuals who remain vulnerable and underserved. The medical community increasingly recognizes the importance of antibody therapy, and the long-term consequences of COVID continue to be serious. From in utero exposure, risk to children, neurological effects, cardiovascular complications, and avoiding infection matters. That perspective is reflected in clinical guidelines.

這並不簡單。我們希望在人們尋求 COVID 防護時能有選擇。我們相信這個選擇具有顯著潛力，因為仍有數以百萬計的個人依然脆弱且未被充分服務。醫療界日益認知抗體療法的重要性，而 COVID 的長期後果仍然嚴重。從子宮內暴露、對兒童的風險、神經學影響、心血管併發症，到避免感染本身都很重要。這樣的觀點也反映在臨床指引中。

Leading organizations, including the Infectious Diseases Society of America and the National Comprehensive Cancer Network, recommend monoclonal antibodies for prevention of SARS-CoV-2 infection in appropriate high-risk patients. This inclusion of PEMGARDA in the NCCN guidelines for B-cell lymphomas underscores that recognition. We are encouraged to see growing interest in utilization across hematology, oncology, rheumatology, infectious disease, transplant neurology, and other appropriate specialties. The adoption curve is expanding. That momentum reinforces our belief in the long-term value of this platform.

包括美國感染症學會（Infectious Diseases Society of America）與美國國家綜合癌症網絡（National Comprehensive Cancer Network）在內的領先組織，建議在適當的高風險患者中使用單株抗體以預防 SARS-CoV-2 感染。NCCN 指引將 PEMGARDA 納入 B 細胞淋巴瘤相關建議，凸顯了這項認知。我們很受鼓舞地看到，在血液學、腫瘤學、風濕免疫科、感染科、移植、神經科及其他適當專科領域，對使用的興趣日益增加。採用曲線正在擴大。這股動能強化了我們對此平台長期價值的信念。

There's a great deal reflected here on this slide. In many of these data points we've discussed on prior calls. I'm pleased that we continue to grow PEMGARDA to serve certain adults and adolescents who are moderately to severely immunocompromised, thus leaving them vulnerable to infection from SARS-CoV-2. What you're seeing is Invivyd building a category. This category has served to expand upon the foundation that is PEMGARDA.

這張投影片反映了許多內容。其中許多數據點我們在先前的電話會議中已討論過。我很高興我們持續擴大 PEMGARDA 的使用，以服務某些中度至重度免疫功能低下的成人與青少年，因而使他們更容易受到 SARS-CoV-2 感染。各位所看到的是 Invivyd 正在建立一個品類。這個品類有助於在 PEMGARDA 這個基礎之上進一步擴展。

Nationally, we see continued growth of accounts who have utilized PEMGARDA, clearly understanding the benefits of protection offered by antibody therapy. We've created this durable foundation with a high degree of accounts reordering PEMGARDA at 77%. We continue to increase available sites of care nationally and across multiple specialties, showing a high confidence for repeat utilization. Our GPO sites of care continue to grow, and the team has been busy providing education at conferences across the nation in hematology, oncology, rheumatology, neurology, pulmonology, transplant, and more.

在全國範圍內，我們看到使用過 PEMGARDA 的客戶帳戶持續成長，且他們清楚理解抗體療法所提供的防護效益。我們建立了這個穩固的基礎，帳戶再訂購 PEMGARDA 的比例達 77%。我們持續在全國及多個專科增加可提供照護的據點，顯示對重複使用具有高度信心。我們的 GPO 照護據點持續成長，團隊也忙於在全國各地的血液學、腫瘤學、風濕免疫科、神經科、胸腔/肺科、移植等會議上提供教育。

As a team that is defining a treatment paradigm, we are in the right places, talking to the right audiences, and our position is strengthening after each engagement. We've secured more than 15,000 contracted GPO sites, significantly expanding our commercial footprint. Taken together, these milestones position us to evolve beyond serving a more limited patient population than we have today with PEMGARDA.

作為正在定義治療典範的團隊，我們出現在正確的地方、與正確的受眾對話，而我們的定位在每次互動後都更加穩固。我們已取得超過 15,000 個簽約的 GPO 照護據點，大幅擴大我們的商業版圖。綜合而言，這些里程碑使我們得以在未來超越目前 PEMGARDA 所服務的相對有限患者族群。

With our next generation monoclonal antibody, we see the potential in redefining COVID prevention, moving toward a vaccine alternative strategy designed to protect broader populations against viral infection. Invivyd's proud to partner with Lindsey Vonn because she exemplifies the power of disciplined preparation as the foundation of enduring strength. In her memoir, Rise: My Story, Lindsey writes, Preparation is the one thing I can control, so I've always controlled it to a capital T.

透過我們的下一代單株抗體，我們看見重新定義 COVID 預防的潛力，朝向一種疫苗替代策略邁進，旨在保護更廣泛族群免於病毒感染。Invivyd 很榮幸與 Lindsey Vonn 合作，因為她體現了以嚴謹準備作為持久力量基礎的力量。在她的回憶錄《Rise: My Story》中，Lindsey 寫道：「準備是我唯一能控制的事，所以我一直把它控制到極致。」

Lindsey prepared an elite level to always perform at her best, and that requires foresight to minimize anything that can get in her way. That mindset really mirrors our approach. Invivyd's monoclonal antibody platform is built on the belief that proactive immune protection, preparing the body before viral exposure, is the most effective way to preserve performance, continuity, and long-term health. Viruses should be kept in check to allow everyone to give their best performance.

Lindsey 以菁英等級的準備，確保自己總能在最佳狀態表現，而這需要前瞻性，以將任何可能阻礙她的因素降到最低。這種心態確實映照了我們的方法。Invivyd 的單株抗體平台建立在一個信念之上：主動的免疫防護——在病毒暴露前先讓身體做好準備——是維持表現、延續性與長期健康最有效的方式。應該將病毒控制在可管理範圍內，讓每個人都能拿出最佳表現。

Staying well helps you continue showing up for the moments that matter. Antibodies can help a person stay well. For this reason, Lindsey is an amazing partner to help educate on the importance of antibodies in all of our well-being.

保持健康能幫助你持續出席那些重要時刻。抗體可以幫助一個人保持健康。因此，Lindsey 是一位很棒的合作夥伴，能協助宣導抗體對我們所有人健康福祉的重要性。

With that, I'll turn the call over to Bill Duke to discuss our financials. Bill?

接下來，我把電話會議交給 Bill Duke，請他說明我們的財務狀況。Bill？

Thanks, Tim. I will quickly review our financials, and then we will open the line for your questions. Our PEMGARDA net revenues continued to grow in the fourth quarter, up 31% over third quarter 2025 and up 25% over fourth quarter 2024. Full net revenues in 2025 totaled $53.4 million, reflecting our continued efforts on driving awareness in the market. After raising over $200 million in the second half of 2025, we ended the year with $226.7 million of cash and cash equivalents. This leaves Invivyd well-capitalized through anticipated pivotal data for VYD2311 in mid 2026 and, depending upon continued PEMGARDA growth and continued operational discipline, potentially well beyond.

謝謝，Tim。我將快速回顧我們的財務狀況，接著我們會開放線路回答各位的問題。我們的 PEMGARDA 淨營收在第四季持續成長，較 2025 年第三季增加 31%，較 2024 年第四季增加 25%。2025 年全年淨營收合計為 5,340 萬美元，反映我們持續推動市場認知的努力。在 2025 年下半年募得超過 2 億美元後，我們在年底的現金及約當現金為 2.267 億美元。這使 Invivyd 在預期於 2026 年年中取得 VYD2311 關鍵性數據之前資金充足；並且視 PEMGARDA 持續成長與持續的營運紀律而定，資金可能可支應更久。

With that, operator, please open the line for questions.

接下來，接線員，請開放線路供提問。

(Operator Instructions)

（接線員指示）

Patrick Trucchio, H.C. Wainwright.

Patrick Trucchio，H.C. Wainwright。

Thanks. Good morning, and congrats on all the progress. Just a couple of follow-up questions from us. Just curious, just, you know, I think it was mentioned that the potential trial resizing decision in the DECLARATION program could occur around April, depending on event rates. Can you talk a little bit more about that? What the specific, you know, statistical criteria that would sort of trigger that decision and what magnitude of enrollment expansion may be needed? Then, just separately, I think, you know, beyond symptomatic PCR-controlled COVID, I'm wondering if you're collecting secondary endpoints such as viral load, symptom duration, or healthcare utilization, and how that could help characterize the, you know, clinical benefit profile that's emerging.

謝謝。早安，也恭喜各位取得所有進展。我們這邊有幾個後續問題。我只是好奇，剛才提到 DECLARATION 計畫中潛在的試驗樣本數調整決策，可能會在 4 月左右發生，取決於事件率。能否再多談一點？具體而言，會觸發該決策的統計標準是什麼？以及可能需要擴增多少招募規模？另外，除了有症狀且 PCR 確認的 COVID 之外，我想了解你們是否正在收集次要終點，例如病毒量、症狀持續時間或醫療資源使用情形，以及這將如何幫助刻畫目前浮現的臨床效益輪廓。

Sure. Thanks for the questions, Patrick. Happy to do my best to enlighten. On your first question on the resizing, you know, everything we do related to powering is, of course, effectively a two-by-two matrix, right? You have to understand both the expected VE for which you are powering and then the number of events that accumulate that would allow you to project a final study power. Right now, as we sit here, we feel pretty good about our progress in the study. All of these algorithms are essentially pre-specified, of course, to avoid the potential for bias. I think the way I would look at it is like this.

當然可以。謝謝你的提問，Patrick。我很樂意盡我所能說明。關於你第一個有關樣本量調整（resizing）的問題，你知道，我們所有與統計把握度（powering）相關的工作，基本上都可以視為一個二乘二的矩陣，對吧？你必須同時理解你用來計算把握度所假設的預期 VE（疫苗效力/有效性），以及累積的事件數量，這些事件數量讓你能推估最終的研究把握度。就目前此刻而言，我們對研究進展感到相當不錯。當然，所有這些演算法本質上都是預先規格化（pre-specified）的，以避免潛在偏差。我想我會這樣看待它。

And again, I'm speaking in concepts because of course we're not at that resizing yet, and we don't know what the next few weeks will hold. I think if we were to not trigger the upsizing trigger, it would be because we are highly confident in our ability to statistically assess even a lower than anticipated VE or hazard ratio. If we do, it really couldn't even be read as, you know, a concern about under-powering as such. It would be simply because the way the trigger is designed, it would serve to potentially add power in case the target efficacy is lower than we might otherwise anticipate.

再說一次，我會用概念來談，因為我們當然還沒到需要調整樣本量的時點，而且我們也不知道接下來幾週會發生什麼。我想如果我們沒有觸發擴大樣本量（upsizing）的觸發條件，那會是因為我們對於即使 VE 或風險比（hazard ratio）低於原先預期，我們仍有高度信心能夠進行統計評估。如果我們確實觸發了，也不能被解讀為，嗯，對於把握度不足（under-powering）之類的擔憂。那純粹是因為觸發機制的設計方式，它會在目標效力可能低於我們原本預期時，提供一個可能增加把握度的手段。

We think of it as really a safety mechanism to try to ensure to the best of our ability, which again is unfortunately subject to that, the best of our ability to support the power of the study in case VE pencils out as lower than our modeling would suggest. The good news in all of that is actually related to the speed of our recruitment. The upsizing target is not particularly onerous. Okay? You can imagine in your mind's eye approximately another 30% of the study or so as an upsize target. Importantly, of course, that cohort would be time-shifted, right? A little deeper into the spring and then into the summer, which you might imagine collectively would add to the probability that you accumulate more cases, for example, in a future COVID wave.

我們把它視為一種安全機制，盡我們所能——當然很不幸仍受限於那些因素——在 VE 最終推算結果低於我們模型所暗示的情況下，仍能支撐研究的把握度。其中的好消息其實與我們招募速度有關。擴大樣本量的目標並不特別吃力。好嗎？你可以在腦中想像，大約再增加本研究約 30% 左右作為擴大目標。而且很重要的是，當然，那個隊列在時間上會往後移（time-shifted），對吧？會更深入到春季，然後進入夏季；你可以想像，整體而言這會提高你在未來 COVID 波段中累積更多病例的機率。

While perfect is unavailable here and we are not endowed with godly insight into the future weeks, what we can confidently say is we are very pleased with what we are seeing, and we truly don't know whether such a resizing would be triggered. I think what is nice to consider is that if it is, we would simply be in a position to feel better about ultimate study powering. I think, you know, stepping back, way back to reflect on this endeavor. Our goal is to have a successful study if that is what the clinical profile of VYD2311 allows.

雖然在這裡不可能做到完美，而且我們也沒有神一般的洞見去預知未來幾週，但我們可以有把握地說，我們對目前看到的情況非常滿意，而我們也真的不知道是否會觸發這樣的樣本量調整。我想值得考慮的一點是：如果真的觸發了，我們只會處在一個對最終研究把握度更有信心的位置。我想，退一步，甚至退很遠來反思這項努力。我們的目標是：如果 VYD2311 的臨床特徵允許，我們希望研究能夠成功。

To the extent that such an upsizing might incur a relatively modest timing and overall financial penalty, I think, you know, we'd rather quote, Make the mistake, unquote, of having upsized and then only later find out we didn't need to than do it the other way around. I hope that adds some level of color around the design and thinking. I think it'll be very difficult for us to elaborate much more because we speak to the street only periodically, and of course, these things occur semi-stochastically, right? We have just recruited up the bulk of the study. We just have the most of the exposure out there, and so far things are looking great. We'll make sure to update you as we go forward.

如果這樣的擴大樣本量只會帶來相對溫和的時程與整體財務代價，我想，嗯，我們寧可「犯錯」去擴大樣本量，之後才發現其實不需要，也不要反過來做。希望這能讓你對設計與思考方式多一些理解。我想我們很難再更深入闡述，因為我們只會定期對市場溝通，而且這些事情的發生也帶有半隨機性（semi-stochastically），對吧？我們剛完成研究的大部分招募。我們剛把大部分暴露（exposure）放到外面，而到目前為止看起來都很棒。我們會在後續進展中確保向你更新。

In terms of secondaries, of course, you can imagine in a study like this we will be recording all manner of interactions between participants and, for example, the healthcare complexes sort of is behind one of the questions you asked. I'm sure a great deal more will always come from this study as it did from CANOPY. I think I would caution on expecting, you know, meaningful powering of low frequency clinical events, e.g., hospitalization or death. I think that would be well beyond the intended power of this exercise. I think that's also for a reason, meaning, at this stage in the game, I think we see pretty clear linear biophysical truth, if not, you know, that's sort of a level beyond plausibility, but let's just say it like that.

至於次要終點（secondaries），當然，你可以想像在這樣的研究中，我們會記錄受試者與例如醫療體系之間各式各樣的互動，這也算是你剛才其中一個問題背後的脈絡。我相信這項研究一定會像 CANOPY 一樣，產出更多內容。但我會提醒大家，不要期待我們能對低發生率的臨床事件（例如住院或死亡）做出有意義的把握度設計。我想那會遠遠超出這次試驗原本的把握度目的。我想這也是有原因的：在這個階段，我們看到的是相當清楚的線性生物物理事實；如果不是的話，那就有點超出合理性了，但我們就先這樣說。

That if you do not get sick from SARS-CoV-2, it is pretty unlikely for you to be hospitalized with SARS-CoV-2 or die from SARS-CoV-2. Our progress as a species, I think, over these last six years has demonstrated that one of the best ways to stay well is to not get sick, and that is really what we are fixated on trying to demonstrate here. I think that's an evergreen principle. I think it has been well elaborated in all manner of these studies. I think those relationships are pretty clear in all of the data, even from the vaccines. Our primary focus is really on a, you know, a, I guess, a revisit of what was an earlier in the pandemic message, don't get sick. Most good things we would think would follow linearly and logically from that.

也就是說，如果你沒有因 SARS-CoV-2 生病，那你因 SARS-CoV-2 住院或死於 SARS-CoV-2 的可能性就相當低。我想我們這個物種在過去六年裡的進展已經顯示，保持健康的最佳方式之一就是不要生病，而這正是我們在此專注想要證明的事情。我想這是一個長青原則（evergreen principle）。我想在各式各樣的研究中都已經被充分闡述。我想這些關係在所有資料中都相當清楚，甚至在疫苗資料中也是如此。我們的主要焦點其實是，嗯，我想算是回到疫情早期的一個訊息：不要生病。我們認為多數好事都會從這點線性且合乎邏輯地延伸而來。

I think that is the regulatory paradigm in which we're pleased to operate. I would suspect that if we are successful going forward, there will be many, many opportunities as our antibodies move into bigger and bigger populations to demonstrate these kinds of things in, you know, classically post-approval registry and other type situations in which we'll all look eagerly to make sure that we're right in effect, that not getting a symptomatic infection following exposure to a virus is just a globally good thing. Again, not trying to be coy or not answer. I think we will collect a lot of stuff. I don't know how meaningful many of those endpoints will be from a quantitative and powering standpoint, but they will certainly be collected.

我想這就是我們樂於運作其中的監管典範（regulatory paradigm）。我猜想如果我們未來進展順利，當我們的抗體進入越來越大的族群時，會有很多很多機會在典型的核准後登錄研究（post-approval registry）及其他類型的情境中去證明這些事情；我們也會都很期待確認我們的判斷在效果上是正確的——也就是在暴露於病毒後不發生有症狀感染，整體而言就是一件全球性的好事。再次強調，我不是想賣關子或不回答。我想我們會收集很多資料。我不確定其中許多終點從定量與把握度角度來看會有多大意義，但它們肯定都會被收集。

That's really helpful. If I could, I'd just like to ask about the measles antibody program. I think there's an update expected in the first half of this year. Can you give us a little bit more detail what the envisioned use case is? Is it outbreak prophylaxis? Is it sort of a pediatric bridge therapy, you know, I suppose before newborns could get the vaccine? Are we looking at more of a broader prevention strategy?

這真的很有幫助。如果可以的話，我想再問一下麻疹抗體計畫。我想今年上半年預期會有更新。你能否多提供一些細節，說明你們設想的使用情境（use case）是什麼？是疫情/群聚爆發時的預防性用藥（outbreak prophylaxis）嗎？還是某種兒科的橋接治療（pediatric bridge therapy），例如在新生兒能接種疫苗之前？或者我們是在看更廣泛的預防策略？

Great. Thanks for asking, and I hope it doesn't, you know, diminish your interest in more when we're in a position to more formally update. I'll just stay in concept land for a little while. Look, you've hit upon the use cases, I think, quite nicely in large part, right? One of the things we very much like about this modality is that there is not a pharmaceutical premise that we, you know, or use case we prosecute separate from what native human immunobiology prosecutes. Why do we all have antibody suites? It is to prevent the presentation of symptomatic disease, to treat and knock down viremia once an infection is established. Yeah, as you note, that means we could use such an antibody theoretically for treating active disease.

很好。謝謝你提問，也希望在我們能更正式更新時，不會因此降低你對更多資訊的興趣。我先在概念層面談一會兒。你其實已經相當到位地點出了這些使用情境，在很大程度上是如此，對吧？我們非常喜歡這種治療模式的一點是：我們並不是在推進一個與人類原生免疫生物學（native human immunobiology）所做之事相分離的藥理前提或使用情境。為什麼我們每個人都有一整套抗體？就是為了預防有症狀疾病的出現，並在感染一旦建立後治療並壓低病毒血症（viremia）。是的，如你所說，這也意味著理論上我們可以用這樣的抗體來治療活動性疾病。

It means we could use. By the way, that is, as we've noted in the past, I think something that, sometimes clinicians will use intravenous immunoglobulin or IVIG to do. You could imagine, of course, responding to outbreaks with essentially ring immunization via monoclonal antibody, which might be, you know, an enhanced way to look at the kinetics and potency of what we're able to put on board relative to vaccination.

這表示我們可以使用。順帶一提，也就是如同我們過去所指出的，我認為有些時候臨床醫師會使用靜脈注射免疫球蛋白（intravenous immunoglobulin，IVIG）來做。當然你可以想像，面對疫情爆發時，基本上可透過單株抗體進行環狀免疫（ring immunization）式的應對；這可能是你知道的，一種更強化的方式，用來檢視我們能夠投入的東西相對於疫苗接種在動力學與效力上的表現。

More generally, you highlighted something there that I think we have been putting a lot of thought into, which is I think you used the concept of bridge to vaccine. We think about it almost more in the sense of vaccine enhancement, meaning, I would just observe, and I think this is non-controversial, children, babies are born without a fully developed adaptive immune system, especially the B-suite.

更一般而言，你在那裡強調了一點，我認為我們一直投入很多思考，也就是我想你用了「銜接到疫苗」（bridge to vaccine）的概念。我們幾乎更傾向把它視為「疫苗增強」，也就是說，我只想觀察一下，而且我認為這沒有爭議：兒童、嬰兒出生時其適應性免疫系統尚未完全發育，特別是 B 細胞那一套。

There are data demonstrating that delaying vaccination actually has the ability to improve the profile of vaccination, meaning higher, more durable titers from vaccinating older and older kids, and potentially lower possibility of seronegativity or failure to seroconvert after vaccination. Not to mention the potential benefits associated with allowing for early childhood, you know, neurocognitive motor development, all these other things.

有資料顯示，延後接種其實能改善疫苗接種的表現特徵，也就是對年齡更大的孩子接種可產生更高、且更持久的抗體效價（titer），並且可能降低血清陰性（seronegativity）或接種後未能血清轉換（seroconvert）的機率。更不用說，讓幼兒早期有時間進行神經認知與動作發展等各種其他事情，可能也有其潛在益處。

Look, we are gonna be in a position we hope to contemplate a lot of things that really, I think the medical complex hasn't been in a position to contemplate before, and that is because justifiably, absent other tools, I think that pediatric schedule is thoughtfully assembled in order to try to have the least vulnerability possible, beginning with vaccination at an early age.

你看，我們希望能處於一個位置去思考很多事情；我認為醫療體系過去其實從未有機會去思考這些，而這是因為在缺乏其他工具的情況下（這也合情合理），我認為兒科接種時程是經過周全設計的，目的在於從很小的年齡開始接種，以盡可能降低脆弱期。

Well, certain antibodies, especially, you know, nirsevimab, Beyfortus, and others, have demonstrated the benefits associated with passive prophylaxis in the very young. There may be other benefits we can explore going forward.

嗯，某些抗體，特別是你知道的 nirsevimab、Beyfortus，以及其他產品，已經證明在非常年幼族群中採取被動性預防（passive prophylaxis）所帶來的益處。未來我們也許還能探索其他益處。

Look, it's premature to say more, although Robert Allen is leaning in. That usually tells me he wants to add something, so I'm gonna stop in a second. I guess I would just say stay tuned because I think we are really intrigued by the potential for some use cases, as you put it, that just have never been contemplated before. I think our view is there's a potential substantial quantum of medical and potentially economic value to create.

你看，現在多說還言之過早，雖然 Robert Allen 正在加入。那通常表示他想補充些什麼，所以我等一下就停。我想我只會說請拭目以待，因為我認為我們對於某些你所說的使用情境（use cases）的潛力非常感興趣，而這些情境過去從未被思考過。我認為我們的看法是：有機會創造相當可觀的醫療價值，並且可能也有經濟價值。

Yeah, I would agree with that answer. I think that the main thrust of this has come from inbound requests from HCPs for something to provide them with a solution in cases where they have a need for treatment or for post-exposure prophylaxis for measles. This antibody has been designed with those use cases in mind as well as some of the potential future use cases that Marc mentioned. That's really where we're headed with this antibody at this point.

是的，我同意那個回答。我認為這件事的主要推力來自醫療照護專業人員（HCPs）的主動需求，他們希望有一個解決方案，用於在需要治療或麻疹暴露後預防（post-exposure prophylaxis）的情況。這支抗體的設計也把這些使用情境納入考量，同時也包含 Marc 提到的一些潛在未來使用情境。就目前而言，這就是我們推進這支抗體的方向。

Terrific. Thanks so much.

太好了。非常感謝。

(Operator Instructions)

（接線員指示）

Tom Shrader, BTIG.

Tom Shrader，BTIG。

Good morning. Congratulations on the progress that I think you're making, positive event comments, and certainly the safety news is fantastic. We've talked a little bit, Marc, about your ability to sculpt the trial a little bit to try to hit hot spot areas. Wonder if you could talk in broad brushstrokes about how well that has gone, and is that in fact self-enforcing that the people who enroll are in fact they know they're in areas where there's a big deal? A more specific question on the myocarditis monitoring. Is that gonna be clinical myocarditis, yes, no, or is that a more detailed study where you're looking at, I don't know, muscle proteins, things like that? Is that a deeper study, or is that just the rare clinical myocarditis event? Thanks.

早安。恭喜你們我認為正在取得的進展、正面的事件（event）評論，當然安全性方面的消息也非常棒。Marc，我們稍早談到你們在試驗設計上能稍微「雕塑」一下，以嘗試鎖定熱點地區。想請你用較概括的方式談談這進行得如何？以及這是否確實具有某種自我強化效果，也就是入組的人其實知道自己在疫情很嚴重的地區？另外一個更具體的問題是關於心肌炎監測。那會是臨床心肌炎的有／無（yes/no）判定，還是更深入的研究，例如你們會看一些我不知道的肌肉蛋白之類的指標？那會是更深入的研究，還是只針對罕見的臨床心肌炎事件？謝謝。

Hey, good morning, Tom. Thanks for the questions. Happy to give you some view here. Okay. Listen, with respect to DECLARATION study, what we've been discussing is on the margin, our ability to have sites that are in areas that are, we believe, undergoing some level of community COVID attack rate, right?

嗨，早安，Tom。謝謝你的問題。很樂意提供一些看法。好。聽著，關於 DECLARATION 研究，我們一直在討論的是在邊際上（on the margin），我們是否有能力讓研究站點位於我們認為正在經歷某種程度社區 COVID 感染攻擊率（attack rate）的地區，對吧？

Yes.

是。

You can see some of that in the ways that we see it, whether it's clinical sequencing, whether it's wastewater sequencing, or sometimes whether it is, for example, you know, emergency department or, you know, sort of, one of those things called the sort of like low acuity, you know, walk-in clinic kind of census data on where people are reporting symptomatic positive COVID.

你可以從我們觀察到的方式看到其中一些跡象，不論是臨床定序、污水定序，或有時例如你知道的急診部門，或所謂的那種低急性（low acuity）的 walk-in 診所之類的人次普查（census）資料，用來看人們在哪些地方回報有症狀且 COVID 檢測陽性。

Look, we operate a US study with a relatively broad catchment area because a lot of this was designed in October, November, December timeframe, and we were not in possession of such a map. You know, we have some ability on the margin to try to place exposures where we see COVID. I think it's also a risk to over interpret the map because these things move, and they move fast.

你看，我們在美國進行一項研究，涵蓋範圍相對廣，因為很多設計是在 10 月、11 月、12 月那段時間完成的，而當時我們並沒有這樣的一張地圖。你知道的，我們在邊際上確實有一些能力，嘗試把暴露（exposures）放在我們看到 COVID 的地方。我也認為過度解讀這張地圖是有風險的，因為這些情況會移動，而且移動得很快。

For example, over the next few weeks or months, to the extent that air conditioning goes on across the US South, the map can move. We feel pretty well prepared and pretty well configured to hopefully keep seeing event accrual. Is it self-reinforcing? I couldn't even begin to answer because it's I've never even contemplated such a thing. I guess I'll leave it as I don't know. I so we'll see in hindsight whether or not there was any discernible behavioral aspect to it. On myocarditis, I think at first pass, this is gonna be a yes no exercise, mainly because the LIBERTY study where we are looking for that is small.

例如，在接下來幾週或幾個月內，若美國南部各地開始開冷氣，這張地圖就可能改變。我們覺得自己準備得相當充分、配置也相當到位，希望能持續看到事件累積（event accrual）。這是否會自我強化？我甚至無從回答，因為我從未想過這種事。我想我就先說我不知道。所以我們會在事後回頭看，是否存在任何可辨識的行為面向。至於心肌炎，我認為第一步這會是一個有／無（yes/no）的判定，主要是因為我們用來觀察這件事的 LIBERTY 研究規模很小。

I think, the risk of overt myocarditis or pericarditis following vaccination is relatively low. Now, like all clinical studies, we gather samples. We will look at data. There can always be room for more detailed exploration or follow-up. Again, if we were to see such an event following vaccination, I think we would become very interested. I wouldn't speak on behalf of the broader scientific or academic community or regulators, but I imagine a lot of people might be interested in that. I just want to double underline myocarditis, pericarditis is not something we see with antibodies, right?

我認為，接種疫苗後發生明顯心肌炎或心包炎的風險相對較低。不過，和所有臨床研究一樣，我們會收集樣本。我們會檢視資料。永遠都可能有空間做更深入的探索或追蹤。再說一次，如果我們在接種後看到這樣的事件，我想我們會變得非常關注。我不代表更廣泛的科學或學術界或監管機構發言，但我想很多人可能都會對此感興趣。我只想再次強調：心肌炎、心包炎不是我們在抗體上會看到的東西，對吧？

Yes.

是。

Of studying, mRNA-based COVID vaccination in our comparative and combination LIBERTY study. Look, I wouldn't -- We'll see, right? I don't know that LIBERTY is certainly not powered or even close to powered to detect --

在我們的比較與合併用藥的 LIBERTY 研究中，研究的是以 mRNA 為基礎的 COVID 疫苗接種。你看，我不會——我們再看吧，對吧？我不認為 LIBERTY 的設計有足夠的統計力（powered），甚至遠遠談不上有足夠的統計力來偵測——

Right.

沒錯。

Events that we would imagine are at that low of frequency, but let's all find out together.

我們想像中那類事件發生頻率很低，但就讓我們一起來看看。

If I can ask a quick follow-up. You apparently have an RSV antibody you like. That would seem to be a high bar that's been a very active area for a long time. Can you give us any detail on maybe what you're improving or how hard do you think it would be to have an antibody that was good enough to take on what's a pretty entrenched competition? Thanks.

如果我可以再追問一個簡短的問題。你們顯然有一個你們看好的 RSV 抗體。這看起來門檻很高，而且這個領域長期以來一直非常活躍。你能否提供一些細節，例如你們可能在改善什麼，或你認為要做出一個足以挑戰目前相當根深蒂固競爭格局的抗體，難度有多高？謝謝。

Sure. now I really saw Dr. Robert Allen's body language change, so I know he's gonna have some thoughts in a second. I would just say this, you know, the RSV antibody field goes back, I believe, to 1998 with palivizumab or Synagis. was really only updated at the molecular level, I wanna say, and forgive me if I'm wrong, in 2023 with the arrival of nirsevimab, Beyfortus.

當然。現在我真的看到 Robert Allen 醫師的肢體語言變了，所以我知道他等一下一定會有一些想法。我只想說，RSV 抗體領域我相信可以追溯到 1998 年的 palivizumab（Synagis）。

Now, nirsevimab is a lovely antibody. I think ours is a lovely antibody, and I think it has some properties that we see as quite compelling. you know, typically in the pharmaceutical industry, when we look at a blockbuster high-growth antibody space, it's hard to sit back and conceive of the fact that that will be the one thing forever and only and always.

現在，nirsevimab 是一個很棒的抗體。我認為我們的也是很棒的抗體，而且我認為它具備一些我們覺得相當有吸引力的特性。

Indeed, at the molecular level, we really like what we're seeing and expect to have the ability to compete. I'll let Robert elaborate in a minute, but I would also just note we look at RSV as a really attractive component of an emerging strategy. You might well notice now as we go from COVID to RSV, perhaps to measles, perhaps onward to other viruses in which having a commercial portfolio and a real presence in pediatrics has the potential to open or expand on a field that is, I would argue, by contrast to your assertion, in its infancy, no pun intended. nirsevimab in year three now is early. I think its dramatic commercial success is a function of the quality of the medicine.

確實，在分子層級上，我們非常喜歡我們所看到的結果，並預期具備競爭的能力。我等一下讓 Robert 再補充，但我也想指出，我們把 RSV 視為一個正在成形的策略中非常有吸引力的一個組成部分。你可能也會注意到，當我們從 COVID 走向 RSV，或許再到麻疹，甚至延伸到其他病毒；在兒科領域擁有商業化產品組合與真正的市場存在感，有機會開啟或擴大一個領域——我會說，與你剛才的說法相反——它其實仍在起步階段，無意雙關。nirsevimab 現在才第三年，仍屬早期。我認為它戲劇性的商業成功，反映的是藥物本身的品質。

To the extent that we feel great about the quality of our medicine, I can say we are very much looking forward to competing. Now that's a long way off, but we have opportunity in front of us to be clever in clinical trial design, to be clever in, you know, some other aspects that might define our overall profile. Now that Robert's good and warmed up, why don't you add color if you think that.

在我們對自家藥物品質非常有信心的前提下，我可以說我們非常期待參與競爭。當然那還有很長一段路，但我們面前有機會在臨床試驗設計上更聰明，也能在一些其他面向更聰明，這些都可能形塑我們整體的產品特徵。既然 Robert 已經熱身好了，如果你覺得需要補充，就請你再多加說明。

I think, you know, what you can know is that we learned a lot in the era of generating COVID antibodies about trying to be upfront about addressing evolutionary drift and recognizing that while there may not be liabilities to our epitope, drift represents a change in context that deserves to be addressed periodically.

我想，你可以知道的是，我們在開發 COVID 抗體的那個時期學到很多，包括要如何在一開始就正面處理演化漂移（evolutionary drift），並認知到即使我們的表位（epitope）可能沒有弱點，漂移也代表情境的改變，值得定期加以因應。

When we look at RSV in the time since, the screening was done for the two known actives that are in the market now, there's been a considerable amount of drift, and really the design of our program was meant to address that and with that drift also address some of the known liabilities for the two known actives, and overcome those liabilities by design. This is where we find ourselves, with a very high-quality antibody that's contextualized by the recent, evolutionary past of that virus.

當我們回頭看 RSV，在當初針對目前市面上兩個已知有效產品完成篩選之後的這段時間裡，已經出現相當程度的漂移；而我們這個專案的設計，就是要因應這點，同時也要在這些漂移之下處理那兩個已知有效產品的一些已知弱點，並透過設計來克服這些弱點。因此我們目前的狀態是：我們擁有一個非常高品質的抗體，而且它是以該病毒近期的演化歷史作為情境背景來打造的。

I think that as we see, with RSV, we can depend on it to drift not as much as COVID, but as far as COV-2 rather, but will drift, and so we will continue to address that as it comes up. It's really the overall strategy that we have with our antibodies is to be very upfront about updating antibodies periodically, to match the environment that we find ourself in. I hope that, I hope that helps.

我想就我們所見，RSV 的漂移幅度不會像 COVID——更精確地說，不會像 SARS‑CoV‑2——那麼大，但它仍然會漂移，因此我們會持續在出現時加以因應。我們抗體的整體策略，就是非常前瞻地定期更新抗體，以符合我們所處的環境。希望——希望這樣有幫助。

Yeah, that's perfect. Thank you.

是的，這非常好。謝謝你。

Thank you. I'm currently showing no further questions at this time. I'd like to hand the call back over to Marc Elia for closing remarks.

謝謝。目前我這邊顯示暫時沒有其他提問。我想把電話交回給 Marc Elia 做結語。

All right. Well, thank you very much all of you for joining us this morning. We will look forward to having, I'm sure, some follow-up calls throughout the day. Have a great day. Thank you.

好的。非常感謝各位今天早上加入我們。我們也期待今天一整天應該會有一些後續的追蹤電話會議。祝各位有美好的一天。謝謝。

This concludes today's conference. Thank you for your participation. You may now disconnect.

今天的會議到此結束。感謝各位的參與。您現在可以掛線。