Invivyd Inc (IVVD) 2025 Q1 法說會逐字稿

Thank you for standing by and welcome to Invivyd's first quarter 2025 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. (Operator Instructions)

感謝您的支持，歡迎參加 Invivyd 2025 年第一季財報電話會議。此時，所有參與者都處於只聽模式。演講者演講結束後，將有問答環節。（操作員指示）

I would now like to hand the call over to Katie Falzone, SVP, Finance. Please go ahead.

現在我想把電話交給財務高級副總裁凱蒂·法爾佐內 (Katie Falzone)。請繼續。

Thank you, operator. A short while ago, we issued a press release announcing our Q1 2025 financial results and business highlights. That press release and the slides that are being used on today's webcast can be found in the Investors section of the Invivyd website under the Press Release and Events & Presentation sections, respectively.

謝謝您，接線生。不久前，我們發布了一份新聞稿，宣布了我們 2025 年第一季的財務表現和業務亮點。該新聞稿和今天的網路廣播中使用的幻燈片分別可以在 Invivyd 網站的「投資者」部分的「新聞稿」和「活動與簡報」部分找到。

Today's discussion will be led by Marc Elia, Chairman of the Vivid Board of Director. He is joined by Tim Lee, Chief Commercial Officer; Bill Duke, Chief Financial Officer; Dr. Robert Allen, Chief Scientific Officer; and Dr. Mark Wingertzahn, Senior Vice President of Clinical Development.

今天的討論將由 Vivid 董事會主席 Marc Elia 主持。與他一同出席的還有商務長 Tim Lee、財務長 Bill Duke、首席科學官 Robert Allen 博士和臨床開發資深副總裁 Mark Wingertzahn 博士。

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.

在今天的討論中，我們將做出前瞻性陳述，其中包括我們的公司和商業策略、我們的研發活動、我們的監管計劃、某些財務預期、我們的未來前景以及其他非歷史事實的陳述。

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 the call, and Invivyd assumes no duty to update such statements.

這些前瞻性陳述屬於《私人證券訴訟改革法案》的範疇，並受各種風險、假設和不確定性的影響，這些風險、假設和不確定性可能隨著時間的推移而發生變化，並導致我們的實際結果與今天明示或暗示的結果存在重大差異。這些前瞻性聲明僅代表通話當日的觀點，Invivyd 不承擔更新此類陳述的義務。

Additional information on the risk factors that could affect Invivyd's business can be found in our filings made with the US Securities & Exchange Commission, including our most recent Form 10-K and 10-Q, which are also available on our website.

有關可能影響 Invivyd 業務的風險因素的更多信息，請參閱我們向美國證券交易委員會提交的文件，包括我們最新的 10-K 表和 10-Q 表，這些文件也可在我們的網站上找到。

I will now turn the call over to Marc.

現在我將把電話轉給馬克。

Good morning and thank you all for joining us.

早安，感謝大家加入我們。

Turning to slide 4. The first quarter and our early second quarter has been a very busy and productive time marked by transition. Our commercial organization is now wholly internalized, new in the field, and reflects an intentional bet by this management team that our new internal team will drive broader adoption of PEMGARDA with associated commercial results. While it is early, our leading indicators are promising, and we remain targeting near-term breakeven with continued revenue growth and operating expense management.

翻到幻燈片 4。第一季和第二季初是一個非常忙碌和富有成效的時期，標誌著一個轉型時期。我們的商業組織現已完全內部化，是該領域的新組織，反映了該管理團隊的有意押注，即我們的新內部團隊將推動 PEMGARDA 的更廣泛採用並帶來相關的商業成果。雖然現在還為時過早，但我們的領先指標令人鼓舞，我們仍以持續的收入成長和營運費用管理為目標，實現近期收支平衡。

Scientifically, we're very pleased with what we see in the evolutionary journey of SARS-CoV-2 relative to the epitope we are exploiting with Pemivibart and as now we see no obstacle to long-term growth in our commercial PEMGARDA business.

從科學角度來看，我們對 SARS-CoV-2 相對於我們正在利用 Pemivibart 的表位的進化歷程感到非常滿意，而且現在我們認為 PEMGARDA 商業業務的長期增長沒有任何障礙。

We have secured access to additional non-dilutive capital to grow if certain conditions and milestones are met, and we are expanding our pipeline to multiple disease areas in which we believe our scientific approach can add value to patients in need.

如果滿足某些條件和里程碑，我們已獲得額外的非稀釋性資本來實現成長，並且我們正在將我們的產品線擴展到多個疾病領域，我們相信我們的科學方法可以為有需要的患者增加價值。

Specifically, we have added discovery programs against new viral targets with the potential for identifying best in-class medicines for diseases outside of COVID-19. Our previous work in influenza continues at a low intensity, but bird flu with pandemic potential has not meaningfully emerged, and in the very recent short time, we have actually seen more US deaths from measles outbreaks than we have seen from avian influenza over the past year or so. At this point, it is reasonable to expect that trend to continue, and our focus has shifted accordingly toward early measles discovery.

具體來說，我們增加了針對新病毒標靶的發現項目，有可能找到 COVID-19 以外疾病的最佳同類藥物。我們之前在流感方面的工作仍然處於低強度，但具有大流行潛力的禽流感尚未出現，而且在最近的短時間內，我們實際上看到美國因麻疹疫情而死亡的人數比過去一年左右因禽流感而死亡的人數還要多。目前，我們有理由預期這個趨勢將會持續下去，我們的重點也隨之轉向早期發現麻疹。

Last year, we initiated a new discovery program for an RSV monoclonal antibody that Robbie Allen, our CSO will describe in a bit more detail. RSV presents a very clear, high-value competitive landscape and some molecular properties we believe we can target to generate a potential best-in-class monoclonal antibody with blockbuster commercial potential.

去年，我們啟動了一項新的 RSV 單株抗體發現計劃，我們的 CSO Robbie Allen 將對此進行更詳細的描述。RSV 呈現出非常清晰、高價值的競爭格局和一些分子特性，我們相信我們可以針對這些特性來產生具有巨大商業潛力的潛在最佳單株抗體。

As we grow and expand our COVID franchise, we will accordingly want to make targeted financially responsible investments in discovery that can yield drugs we can capitalize for development either in concert with the equity markets or with potential strategic partners. There has been no shortage of interest in our work from potential partners, particularly those with a vaccine footprint.

隨著我們 COVID 特許經營權的成長和擴大，我們將相應地希望對發現進行有針對性的財務負責投資，這些投資可以產生我們可以利用其進行開發的藥物，無論是與股票市場合作還是與潛在的戰略合作夥伴合作。潛在合作夥伴對我們的工作一直很感興趣，尤其是那些有疫苗接種經驗的合作夥伴。

It's important to note that our corporate goals, including targeting near-term breakeven, are audacious by design and reflective of our integrated strategic and operational choices. In the big picture, we want to create as much medical value for patients in society as fast as possible, and then we want to translate that value into per share shareholder value as efficiently as possible.

值得注意的是，我們的企業目標（包括短期收支平衡目標）在設計上是大膽的，反映了我們的綜合策略和營運選擇。從整體來看，我們希望盡快為社會患者創造盡可能多的醫療價值，然後盡可能有效率地將該價值轉化為每股股東價值。

In an easy biotech financing environment characterized by low interest rates and long return horizons with blue skies for investors, it is much easier for companies to raise large quantities of dilutive equity that may enable a mediocre or far-fetched biological premise to survive to the next catalyst. But such a business strategy rarely translates into long-term per-share compounding of shareholder value.

在寬鬆的生物技術融資環境中，低利率、長期回報期以及投資者的樂觀前景，公司更容易籌集大量稀釋性股權，這可能使平庸或牽強的生物前提得以生存到下一個催化劑。但這樣的商業策略很少能轉化為股東價值的長期複合成長。

We are taking the opposite approach and trying to be highly disciplined with our expenditures and capital base to the maximum extent, and not just because these days the biotech investing backdrop and equity cost of capital has been tougher.

我們採取了相反的方法，試圖在最大程度上嚴格控制我們的支出和資本基礎，這不僅是因為如今生技投資背景和股權資本成本更加嚴峻。

We've been taking our approach because we see full operational proof of concept in our ability to make medicines rapidly and efficiently, and we wish to exploit that advantage, which we see as unique in the industry as we grow our business so that our shareholders can benefit accordingly.

我們一直採取我們的方法，因為我們看到了我們快速高效地生產藥品的能力的完整操作概念證明，並且我們希望利用這一優勢，我們認為這一優勢在行業中是獨一無二的，因為我們發展業務，以便我們的股東能夠相應地受益。

Turning to slide 5, in the bigger social picture, it is important to note that our fundamental corporate strategy reflects a great many macro-level realities that have also undergone transition, specifically a US election result and new public health leadership focused on chronic disease who are moving in directions on multiple fronts that comport well with our business strategy.

翻到投影片 5，在更大的社會背景下，值得注意的是，我們的基本企業策略反映了許多也經歷了轉變的宏觀現實，特別是美國大選結果和專注於慢性病的新公共衛生領導層，他們正在朝著與我們的業務戰略相符的多個方面的方向發展。

It's a quick reminder, Invivyd was started based on a simple reality that SARS-CoV-2 was a unique virus designed to prey on a distinctly vulnerable human population. It was clear early that vaccines for COVID-19 disease would work over the short term, but that waning responses would be problematic for every person, especially for immunocompromised persons. And on top of that, immune-invasive Omicron viruses have added another headwind, as has the growing underlying burden of long COVID.

簡單提醒一下，Invivyd 的創立基於一個簡單的現實：SARS-CoV-2 是一種獨特的病毒，其目的是攻擊特別脆弱的人類群體。很早就清楚，COVID-19 疫苗在短期內會起作用，但疫苗反應的減弱對每個人來說都是有問題的，尤其是對免疫功能低下的人來說。除此之外，免疫侵入性 Omicron 病毒也帶來了另一個不利因素，長期 COVID 的潛在負擔也日益加重。

More, given the handling of COVID-19 vaccine policies, there is a regrettable secular shift underway with respect to American attitudes toward vaccination as a whole. Reviewing the last year's events with respect to COVID-19 vaccines, such a shift is indeed regrettable, but perhaps not surprising.

此外，考慮到對新冠疫苗政策的處理，美國人對疫苗接種的態度正在發生令人遺憾的長期轉變。回顧去年新冠疫苗的進展，這種轉變確實令人遺憾，但或許並不令人意外。

Monoclonal antibodies can be designed to overcome challenges with vaccination. After all, we are all born immunocompromised and preloaded with a suite of non-self-monoclonal antibodies from our mothers. And yet, in the pursuit of freedom from the burden of SARS-CoV-2, our regulatory and public health complex for four years was single-mindedly focused on exposing humans serially and broadly to spike protein, largely in mRNA form, in an effort to get us our protective antibodies the hard way rather than, as mom and mother nature might suggest, providing mechanisms for humans to access additional antibody support so that humans don't need to choose between dangerous infections and increasingly debatably effective vaccinations.

單株抗體可以被設計來克服疫苗接種的挑戰。畢竟，我們生來就免疫功能低下，並從母親那裡預先獲得了一套非自身單株抗體。然而，為了擺脫 SARS-CoV-2 的負擔，我們的監管和公共衛生體系四年來一門心思專注於讓人類連續廣泛地接觸刺突蛋白（主要是 mRNA 形式），試圖讓我們以艱難的方式獲得保護性抗體，而不是像大自然母親可能建議的那樣，為人類提供獲得額外抗體支持的機制，這樣人類就不必在危險的感染和有效疫苗之間做出越來越有爭議的疫苗之間。

Unique in the industry, Invivyd has now fully developed through multiple placebo-controlled RCTs, two monoclonal antibodies against SARS-CoV-2, adintrevimab against ancestral viruses like Delta, and now pemivibart against contemporary immune-invasive Omicron viruses.

Invivyd 在業界獨樹一幟，目前已透過多項安慰劑對照 RCT 全面開發出兩種針對 SARS-CoV-2 的單株抗體、針對 Delta 等祖先病毒的 adintrevimab，以及現在針對當代免疫侵襲性 Omicron 病毒的 pemivibart。

More in our recent canopy Phase 3 clinical study assessing safety, immuno bridging, and exploratory clinical efficacy analysis, we are reporting clinical results from a modern American population, specifically a population that has pre-existing immune experience or seropositivity in both study and placebo arms. To some observers of the vaccine industry, conducting such studies is undoable or unthinkable. And yet to us and others in the monoclonal antibody business, those studies are business as usual.

在我們最近評估安全性、免疫橋接和探索性臨床療效分析的 3 期臨床研究中，我們報告了來自現代美國人群的臨床結果，特別是在研究組和安慰劑組中均具有預先存在的免疫經驗或血清陽性的人群。對一些疫苗產業觀察家來說，進行這類研究是不可行或不可想像的。然而對於我們以及單株抗體產業的其他人來說，這些研究一切正常。

You will see elements of our recent Citizen Petition to the US FDA that focuses in on these issues because to us there is clearly within reach a mechanism to scale access to monoclonal antibodies if and when regulators so choose. As you will see later in this morning's call, we have multiple parallel conversations with public health authorities designed to expand the consequences of our discovery and development work.

您會看到我們最近向美國 FDA 提交的公民請願書中重點關注這些問題，因為對我們來說，如果監管機構選擇這樣做，顯然可以建立一種機制來擴大單株抗體的獲取管道。正如您將在今天早上的電話會議中看到的，我們與公共衛生當局進行了多次平行對話，旨在擴大我們的發現和開發工作的後果。

With that, I'll turn the call over to Tim Lee to discuss our commercial progress in the quarter.

說完這些，我將把電話轉給 Tim Lee，討論我們本季的商業進展。

Thank you, Marc, and good morning all. Turning to slide 6.

謝謝你，馬克，大家早安。翻到幻燈片 6。

The first quarter cemented our transition from a contracted largely outsourced model designed to hit a short seasonal window to a best-in-class commercial footprint to drive consistent growth via an in-house team.

第一季鞏固了我們的轉型，從旨在滿足短暫季節性需求的合約外包模式，向一流的商業足跡模式轉變，透過內部團隊推動持續成長。

We did not have a fourth quarter call, so it's been six months since I've had the opportunity to speak with the broad investor community and it's worth sharing a few general observations from the fall and winter before we walk through key indicators.

我們沒有召開第四季度電話會議，因此我已經六個月沒有機會與廣大投資者群體交談了，在我們討論關鍵指標之前，值得分享一些秋季和冬季的一般觀察結果。

Marc and the team asked me to create a best in class commercial effort to put behind PEMGARDA and our future molecules. I'm pleased with what we've done so far, but in many ways, we are just getting started.

馬克和團隊要求我創造一流的商業努力來支持 PEMGARDA 和我們未來的分子。我對我們迄今為止所做的工作感到滿意，但從很多方面來看，我們才剛剛開始。

First, we spent an enormous amount of time with healthcare providers and health systems simply re-educating on the existence of monoclonal antibodies as an alternative therapy available today.

首先，我們花了大量時間與醫療保健提供者和衛生系統重新宣傳單株抗體作為當今可用的替代療法的存在。

What began as a commercial interest largely driven by those who knew and anticipated PEMGARDA now beginning to see institutional orders that are just beginning to reflect the underlying medical need.

最初，這主要是由那些了解並預見到 PEMGARDA 的人出於商業利益而推動的，現在，他們開始看到機構訂單，這些訂單才剛開始反映出潛在的醫療需求。

Protocols, pathways, real-world experience and word of mouth in the clinical community are still in the early innings, and we expect real growth to follow as this familiarity rises.

臨床界的協議、途徑、現實世界的經驗和口碑仍處於早期階段，我們預期隨著熟悉度的提高，真正的成長將隨之而來。

Second, healthcare providers began with real skepticism on the ability of PEMGARDA to navigate virus evolution, particularly filing the FDA's misguided and harmful insertion of inaccurate third-party virology data into the PEMGARDA fact sheet last fall. The combination of our communication of the underlying science and along with the empirical reality of the attractive continuing activity is now gaining notice and belief.

其次，醫療保健提供者開始對 PEMGARDA 控制病毒進化的能力持懷疑態度，尤其是去年秋天 FDA 將不準確的第三方病毒學數據誤導性和有害地插入 PEMGARDA 情況說明書中。我們對基礎科學的交流以及對有吸引力的持續活動的經驗現實的結合現在正獲得關注和信任。

Third, the understanding of COVID-19 of the community has undergone a notable evolution. Most healthcare providers are now moving beyond the pandemic era, concept of an acute respiratory syndrome, the SARS part of SARS-CoV-2 and now see acute infection and corresponding respiratory disease as part of a much broader, more insidious, long-term health challenge.

第三，社會對新冠肺炎疫情的認識有了顯著變化。大多數醫療保健提供者現在已經超越了大流行時代、急性呼吸道綜合徵的概念、SARS-CoV-2 中的 SARS 部分，現在將急性感染和相應的呼吸道疾病視為更廣泛、更隱蔽、更長期的健康挑戰的一部分。

We are, and we believe now on the forefront of educating these clinicians on why patients who are battling cancer, navigating transplant, or who lack sufficient immune cells to mount a response to vaccination need a protective option. The untapped market potential ahead of us remained numerically vast. As we execute in our new posture, we expect to see a meaningful acceleration in product growth.

我們現在處於教育這些臨床醫生的最前沿，我們相信，他們應該明白為什麼那些正在與癌症作鬥爭、準備接受移植或缺乏足夠免疫細胞來對疫苗產生反應的患者需要一種保護性選擇。我們面前尚未開發的市場潛力仍然巨大。隨著我們以新的姿態執行，我們期望看到產品成長的顯著加速。

Now I can get into the specifics of execution on slide 7.

現在我可以講一下第 7 張投影片上的執行細節。

You see here the top-level metrics accompanied by three of the structural elements we have installed at Invivyd. We have moved to a focused, trained, in-house team, ending our relationship with contract representatives. We have established and built a culture of accountability and measurement.

您可以在這裡看到我們在 Invivyd 安裝的三個結構元素以及頂級指標。我們已經轉向一支專注、訓練有素的內部團隊，結束了與合約代表的關係。我們已經建立並培養了一種問責和衡量的文化。

We have substantially refined our messaging and believe that we are recognized as leaders in the COVID-19 field by healthcare providers and institutions broadly. All of these elements are the keys to each successful launch in pharmaceutical growth-initiator nation over my career.

我們已經大幅改進了我們的資訊傳遞方式，並相信我們已被醫療保健提供者和機構廣泛認可為 COVID-19 領域的領導者。在我的職業生涯中，所有這些因素都是在製藥成長啟動國每次成功推出產品的關鍵。

We're also beginning to make some progress around numerous fronts including contracting. While not contemplated in the very early launch, we are receiving scaled interest from organizations who wish to derive value from commitments to our large ordering and are pleased to be working with them. We're seeing ourselves placed in pathways, protocols, and guidelines nationally, leading to a deeper understanding of PEMGARDA.

我們也開始在包括承包在內的許多方面取得一些進展。雖然在初期推出時並未考慮到這一點，但我們正在收到一些組織的關注，他們希望從對我們的大額訂單的承諾中獲得價值，並很高興與他們合作。我們看到自己在全國範圍內處於道路、協議和指南之中，從而對 PEMGARDA 有了更深入的了解。

Turn to sliding slide 8 shows the continued steady growth in our commercial reach. While Q1 revenues dipped from Q4, we believe much of that is attributable to the lack of feet on the street. In January and February, as we trained up and deployed, hired our new sales team, encouragingly, we've seen strong revenues thus far in Q2, including, for example, our biggest-ever commercial day and biggest-ever commercial week. Day by day, the highs are getting higher, and the lows are getting higher as well. This is the hallmark of ongoing growth.

翻到投影片 8，可以看到我們的商業影響力持續穩定成長。儘管第一季的營收較第四季有所下降，但我們認為這在很大程度上是由於缺乏實體店經營者造成的。一月和二月，隨著我們進行培訓和部署，並聘請了新的銷售團隊，令人鼓舞的是，到目前為止，我們在第二季度取得了強勁的收入，例如，我們有史以來最大的商業日和有史以來最大的商業週。日復一日，高點越來越高，低點也越來越高。這是持續增長的標誌。

Turn to slide 9. We would note that professional societies and guideline writers are taking notice of our work. In addition to the IDSA guidelines, we now have PEMGARDA in the NCCN guidelines for B-cell lymphomas, which is a substantial US population which deserves high-quality protection.

翻到第 9 張投影片。我們注意到專業協會和指南編寫者正在關注我們的工作。除了 IDSA 指南之外，NCCN 的 B 細胞淋巴瘤指南中現在也有 PEMGARDA，美國相當一部分人群應該得到高品質的保護。

We routinely see from KOLs at medical conferences an awareness of non-relapsed death, for example, among patients who undergo CAR-T therapy or deep immune ablation to manage lymphomas, and infectious disease deaths is a major contributor to that. With an infectious disease, COVID-19 is again a dominating contributor to that.

我們經常在醫學會議上看到 KOL 對非復發死亡的認識，例如，在接受 CAR-T 療法或深度免疫消融治療淋巴瘤的患者中，傳染病死亡是造成這種情況的主要原因。作為一種傳染病，COVID-19 再次成為造成此現象的主要因素。

Moving to slide 10. Of course, in contrast to other infectious diseases, COVID is ever present and characterized by periodic waves, while the sales of COVID-19 treatments are highly influenced by surges and disease and we saw that clearly among certain bigger pharmaceutical companies in their Q1 earnings calls. Prevention via monoclonal antibody may be a bit more predictable and steady. COVID is always a threat for these populations.

移至投影片 10。當然，與其他傳染病相比，COVID 始終存在並具有週期性波動的特徵，而 COVID-19 治療藥物的銷售受到激增和疾病的嚴重影響，我們在某些​​大型製藥公司的第一季財報電話會議上清楚地看到了這一點。透過單株抗體進行預防可能更可預測且更穩定。COVID 對這些人群始終是一個威脅。

As we go into the warmer months, we tend in the US to see waves of COVID-19 among the southern states and we're launching a targeted digital campaign regarding the likely summer surge, accordingly.

隨著天氣變暖，美國南部各州往往會出現新冠疫情浪潮，因此，我們正在針對可能出現的夏季疫情激增發起有針對性的數位宣傳活動。

Finally, on slide 11. On pricing, we took in March a modest price increase, and still PEMGARDA remains one of the lowest priced antibodies ever launched. Obviously, the original pricing analysis contemplated larger volumes, and potentially lower risk and lower acuity patients, and especially consider the potential for COVID-19 treatment. With treatment off the table for the moment, we took a small price increase to better reflect the value this medicine brings to populations in need.

最後，在第 11 張投影片上。在定價方面，我們在 3 月進行了小幅漲價，但 PEMGARDA 仍然是有史以來價格最低的抗體之一。顯然，最初的定價分析考慮了更大的治療量，以及潛在更低風險和更低敏銳度的患者，並特別考慮了 COVID-19 治療的潛力。由於目前無法進行治療，我們稍微提高了價格，以更好地反映這種藥物為有需要的人群帶來的價值。

Note, the price increase only took effect in March and will be updated by CMS beginning in July.

請注意，價格上漲僅在 3 月生效，並將於 7 月由 CMS 更新。

Next slide, please. We're pleased that PEMGARDA continues to be available through EUA and maintain focused commitment on serving the immunocompromised community.

請看下一張投影片。我們很高興 PEMGARDA 能夠繼續透過 EUA 獲得，並繼續專注於為免疫功能低下的社區提供服務。

I'll now turn the call over to Robbie to discuss some of our progress in research and development. Robbie?

現在我將把電話轉給羅比，討論我們在研發方面的一些進展。羅比？

It's an exciting time to be an infectious disease prevention and treatment as the central authorities in the United States reconsider the state of the world for COVID-19 and beyond. I'll begin on slide 14 by commenting on our now multi-year work with antibodies directed against the receptor binding domain or RBD of the SARS-CoV-2 spike protein. This is obviously a validated target and has been targeted repeatedly by our colleagues and competitors and other companies who would like to produce highly effective treatments and preventatives for COVID-19.

隨著美國中央政府重新考慮 COVID-19 及以後的世界形勢，對於傳染病預防和治療來說，這是一個令人興奮的時刻。我將從第 14 張投影片開始評論我們目前針對 SARS-CoV-2 刺突蛋白的受體結合域或 RBD 的抗體進行的多年研究。這顯然是一個經過驗證的目標，我們的同事、競爭對手和其他想要生產高效 COVID-19 治療和預防藥物的公司已經多次將這一目標作為目標。

The challenge they and we faced and that we believe we are overcoming is evolutionary. Invivyd's proprietary technologies are designed to yield antibody medicines that target special real estate on a biological target in motion such as SARS-CoV-2.

他們和我們所面臨的挑戰以及我們相信我們正在克服的挑戰是進化的。Invivyd 的專有技術旨在生產針對運動中的生物標靶（例如 SARS-CoV-2）上的特殊區域的抗體藥物。

So far, pemivibart has been a total success on that front when we, back of the envelope, calculate the sheer number of mammalian SARS-CoV-2 infections and consider the quantitative dynamics of infections, the fidelity of the SARS-CoV-2 polymerase, et cetera.

到目前為止，當我們粗略計算哺乳動物 SARS-CoV-2 感染的絕對數量並考慮感染的定量動態、SARS-CoV-2 聚合酶的保真度等時，pemivibart 在這方面取得了全面成功。

We began to estimate that the virus has explored quadrillions of molecular variants over the past years, and throughout the epitope that defines the pemivibart binding site has remained structurally intact. Accordingly, the product potency as assessed in best-in-class industrial systems has remained accordingly stable.

我們開始估計，該病毒在過去幾年中已經探索了數千萬億種分子變體，並且定義 pemivibart 結合位點的整個表位在結構上仍然保持完整。因此，在最佳工業系統中評估的產品效力保持穩定。

Reassuringly, of course, for our pipeline molecule 2311 -- VYD2311, the same is true on EC50 values are holding more stable and much more potent levels. In fact, neither the measured potency nor any change for VYD2311 would be visible if we placed our neutralization data onto the chart at the bottom of the slide 14.

當然，令人放心的是，對於我們的管道分子 2311——VYD2311，EC50 值也是如此，保持更穩定和更有效的水平。事實上，如果我們將中和數據放到投影片 14 底部的圖表上，那麼測量的效力和 VYD2311 的任何變化都不會被看到。

Why? Slide 15 shows a graphical depiction of the SARS-CoV-2 spike protein with a blue area shaded indicating the pemivibart epitope. Genetic and structural change observed over time at each amino acid residue in the spike is represented by intensity, yellow for minor, orange for moderate, and reddish for substantial change.

為什麼？投影片 15 顯示了 SARS-CoV-2 刺突蛋白的圖形描述，其中藍色陰影區域表示 pemivibart 抗原決定基。刺突中每個胺基酸殘基隨時間的遺傳和結構變化以強度表示，黃色表示輕微變化，橙色表示中等變化，紅色表示顯著變化。

You will note some yellow in a few spots of our epitope. But that change was all in the Omicron transition. Ever since then, three years, which can be in some ways considered a new phase of the pandemic or a very different endemic phase, our binding site has remained quiescent.

您會注意到我們的表位的幾個點上有一些黃色。但這種變化全都發生在 Omicron 轉型期間。從那時起的三年裡，從某種程度上可以被認為是大流行的新階段或非常不同的流行階段，我們的結合位點一直保持靜止。

More, as vaccination rates have dropped, pressure applied to the RBD at the population level has also dropped. Even more intriguing data out of the Bloom Lab at Fred Hutchinson demonstrates that children who have not been vaccinated, but who have been primarily infected by XVB virus variants appear to generate antibodies suites directed more towards the internal domain and away from RBD.

此外，隨著疫苗接種率下降，RBD 在人口層面承受的壓力也下降了。來自弗雷德哈欽森布魯姆實驗室的更有趣的數據表明，未接種疫苗但主要感染了 XVB 病毒變體的兒童似乎會產生更多針對內部領域而遠離 RBD 的抗體套件。

While these NTD mutations are in keeping with the known immune-invasive properties of Omicron variants, there appears to be less evidence of selective pressure that those classically and historically antigenic sites on RBD near the pemivibart binding site and viruses isolated from these more recent childhood infections. In short, we feel very good about continued PEMGARDA activity over the long term based on the observed stability of the pemivibart epitope.

雖然這些 NTD 突變與 Omicron 變異體已知的免疫侵襲特性相符，但與 RBD 上靠近 pemivibart 結合位點的經典和歷史抗原位點以及從這些較近期的兒童感染中分離出的病毒相比，選擇壓力的證據似乎較少。簡而言之，根據觀察到的 pemivibart 表位的穩定性，我們對 PEMGARDA 的長期持續活性感到非常滿意。

Slide 16 provides a little more color on a discovery program we are moving through now related to RSV. Respiratory syncytial virus is a major medical burden, and there's a well-developed commercial category devoted to the use of monoclonal antibodies to prevent infection in neonates in children under two years at risk from seasonal RSV.

投影片 16 更詳細地介紹了我們正在進行的與 RSV 相關的發現程序。呼吸道合胞病毒是一種主要的醫療負擔，目前已有一個成熟的商業類別致力於使用單株抗體來預防兩歲以下新生兒感染季節性呼吸道合胞病毒的風險。

At present, nirsevimab or Vifordis is the class-leading antibody, although pavilizumab is still used and Merck's clesrovimab has a near-term PDUFA date. The two more contemporary antibodies have certain strengths and liabilities, and variation of the target of protein makes the RSV landscape an excellent opportunity to see if our platform can generate an attractive medicine to compete with the class leaders. In our screening and engineering, we can establish certain parameters designed to yield best-in-class properties, and we will look forward to updating on our progress later this year.

目前，nirsevimab 或 Vifordis 是同類中領先的抗體，儘管 pavilizumab 仍在使用，而默克公司的 clesrovimab 的 PDUFA 日期也即將到來。兩種較現代的抗體具有一定的優勢和劣勢，而蛋白質標靶的變化使 RSV 領域成為一個絕佳的機會，可以看看我們的平台是否可以產生一種有吸引力的藥物來與同類領先產品競爭。在我們的篩選和工程中，我們可以建立某些參數，旨在產生一流的效能，我們期待在今年稍後更新我們的進展。

Slide 17 provides further detail on our recently announced measles discovery program. By degree, measles shares some of the same features as COVID and RSV in terms of multiple circulating variants that require an engineered, broadly neutralizing monoclonal antibody, but which also presents a highly validated antibody target considering the generally understood efficacy of, for example, both MMR vaccine and IVIG in the post-exposure prophylaxis setting.

幻燈片 17 提供了我們最近宣布的麻疹發現計劃的更多詳細資訊。從程度上來說，麻疹與 COVID 和 RSV 具有一些相同的特徵，即有多種傳播變體，需要經過工程改造的、廣譜中和的單株抗體，但考慮到 MMR 疫苗和 IVIG 在暴露後預防環境中的普遍理解的功效，麻疹也呈現出經過高度驗證的抗體靶點。

We have begun our work and our goal would be a tool useful for the treatment of acute infection and also useful in post-exposure or even pre-exposure prophylaxis use cases. We will look forward to reporting on our progress before the end of this year.

我們已經開始工作，我們的目標是開發一種可用於治療急性感染的工具，並且可用於暴露後甚至暴露前的預防用途。我們期待在今年年底前報告我們的進展。

I'll now turn the call over to Mark Wingertzahn and Marc Elia to discuss clinical and regulatory.

現在我將把電話轉給 Mark Wingertzahn 和 Marc Elia 討論臨床和監管問題。

Thanks, Robbie. Good morning, everyone. In early February, we reported our initial progress with VYD2311, our next generation antibody designed to improve pemivibart.

謝謝，羅比。大家早安。2 月初，我們報告了 VYD2311 的初步進展，VYD2311 是我們旨在改進 pemivibart 的下一代抗體。

As a reminder on slide 19, all Invivyd COVID-19 antibodies share identical scaffolding, and generally, our discovery product process works such that each successive monoclonal antibody is a minor but essential tweak from the last.

正如幻燈片 19 中所提醒的那樣，所有 Invivyd COVID-19 抗體都具有相同的支架，並且通常，我們的發現產品流程是這樣的，每個連續的單株抗體都與上一個有微小但重要的調整。

This process results in molecules that are near identical in terms of amino acid sequence, in fact, generally changed about to a similar or even lesser extent than, let's say, mRNA COVID vaccines from one generation to the next.

這一過程產生的分子在氨基酸序列方面幾乎相同，事實上，與 mRNA COVID 疫苗相比，其從一代到下一代的變化程度大致相同，甚至更小。

With VYD2311, we are not trying to solve a problem related to variation or some threats to our pemivibart activity, rather, we are trying to engineer more medically and commercially attractive features into our medicines.

對於 VYD2311，我們並不是試圖解決與變異相關的問題或對我們的 pemivibart 活動的某些威脅，而是試圖在我們的藥物中設計出更具醫學和商業吸引力的特性。

Slide 20 quickly outlines our first in-human dose and route of administration ranging clinical trial designed to provide maximum forward flexibility for our go to markets and regulatory conversations. You can see the cohorts on the slide and the concepts behind assessing them initially. We will be wrapping up the study soon and we will be pleased to provide an update in next week's on our progress.

幻燈片 20 快速概述了我們的首次人體劑量和給藥途徑範圍臨床試驗，旨在為我們的市場進入和監管對話提供最大的前向靈活性。您可以在幻燈片上看到群組以及最初評估它們背後的概念。我們將很快完成這項研究，並將很高興在下週提供我們的進展更新。

Turning to slide 21, it reminds us very quickly the properties of VYD2311 relative to the pemivibart and what we think those properties allow for. It is our belief that 2311 can be a major step forward for people sick with COVID-19 and people highly vulnerable to COVID-19, whether immunocompromised or not.

翻到第 21 張投影片，它很快就提醒了我們 VYD2311 相對於 pemivibart 的特性，以及我們認為這些特性所允許的作用。我們相信，對於 COVID-19 患者和極易感染 COVID-19 的人來說，2311 可以是一個重大的進步，無論免疫功能是否低下。

VYD2311 represents a potential step change in accessibility and scalability for protection compared to PEMGARDA and may present the opportunity to also create a highly efficient and effective treatment.

與 PEMGARDA 相比，VYD2311 代表了保護的可近性和可擴展性的潛在重大變化，並可能提供創造高效和有效治療方法的機會。

With that, I'd like to turn the call back to Mark Elia, who will discuss our regulatory experience with our COVID-19 treatment EUA request and some next steps. Marc.

說到這裡，我想把電話轉回給馬克·埃利亞 (Mark Elia)，他將討論我們在 COVID-19 治療 EUA 請求方面的監管經驗以及一些後續措施。馬克。

Thank you, Marc. As previously mentioned, we've been watching evolution at HHS and FDA with great interest. One of the key messages new HHS and FDA leadership has sent has been the desire for greater transparency, especially as it relates to communication between FDA and industrial sponsors.

謝謝你，馬克。如前所述，我們一直非常感興趣地關注著 HHS 和 FDA 的發展。新任衛生與公眾服務部和 FDA 領導層發出的關鍵訊息之一是希望提高透明度，特別是在 FDA 與工業贊助商之間的溝通方面。

At this time, we have not seen any convention emerge on this front among our colleagues in industry, nor do we have any guidance on this topic from the agency. However, we are aligned with the notion that transparency is a generally good thing for regulators, patients, sponsors, and citizens.

目前，我們還沒有看到業內同行就此達成任何共識，也沒有收到機構就此問題提供的任何指導。然而，我們一致認為，透明度對於監管機構、患者、贊助商和公民來說通常是一件好事。

With that in mind and given the sheer volume of correspondence companies like ours have with FDA, we are today beginning by providing direct excerpts and data from one recent correspondence back in February, specifically the declination by the legacy Biden FDA of our application for expansion of our EUA to include treatment of active mild to moderate COVID in immunocompromised persons with no treatment options. This action generated many questions to our company from HCPs and patients, and we hope that today's presentation provides some answers.

考慮到這一點，並考慮到像我們這樣的公司與 FDA 的通信量巨大，我們今天首先提供 2 月份最近一封通信的直接摘錄和數據，特別是拜登原 FDA 拒絕了我們擴大 EUA 的申請，以包括治療沒有治療選擇的免疫功能低下人群中的輕度至中度活躍人群中的輕度至中度 COVID COVID。這項措施引發了醫護人員和病患對我們公司的諸多疑問，我們希望今天的演示能提供一些答案。

Importantly, we believe our presentation today reflects both the core of the scientific review by the agency and the bulk of their communication to us on the topic and would resemble in some ways the major points the agency might render to, for example, an advisory committee, if that were an operative forum. We are including our rebuttals to those points, which ultimately will build to our intended next steps.

重要的是，我們相信，我們今天的陳述既反映了該機構科學審查的核心，也反映了他們就該主題與我們溝通的大部分內容，並且在某些方面類似於該機構可能向例如諮詢委員會（如果這是一個操作論壇）提出的主要觀點。我們正在對這些觀點進行反駁，這最終將有助於我們採取下一步行動。

Importantly, at Invivyd, we are Americans and taxpayers, and some of us are patients too, in addition to industrial sponsors, and so we view our partnership with FDA as fundamentally collaborative on behalf of patients in need.

重要的是，在 Invivyd，我們是美國人和納稅人，除了工業贊助商之外，我們中的一些人也是患者，因此我們認為與 FDA 的合作從根本上來說是為了有需要的患者而進行的合作。

Slide 22 describes the operative background. Immuno bridging of antibodies for COVID-19 has its roots in a December 2022 joint EMA FDA webinar attended by regulators and academic and industrial experts, including Invivyd, and was devoted to accelerating COVID-19 monoclonal antibody development.

投影片 22 描述了操作背景。COVID-19 抗體的免疫橋接源於 2022 年 12 月 EMA FDA 聯合網路研討會，監管機構以及包括 Invivyd 在內的學術和工業專家參加了該研討會，致力於加速 COVID-19 單株抗體的開發。

In our case, our immuno bridging prototype molecule adintrevimab went through full Phase 3 registrational RCTs for both prep and treatment of COVID-19, and as such, adintrevimab represents a biophysical profile well associated with demonstrated placebo-controlled clinical efficacy.

在我們的案例中，我們的免疫橋接原型分子 adintrevimab 已完成針對 COVID-19 的預防和治療的完整 3 期註冊 RCT，因此，adintrevimab 代表了與已證實的安慰劑對照臨床療效密切相關的生物物理特徵。

Industry, academic, and regulatory confidence in sVNA titer or clinical antibody antiviral activity is sufficiently high to use that surrogate as a way to bridge from one clinical dataset to a new molecule without the need for full pre-authorization clinical studies, just as we did for our prep authorization.

產業、學術界和監管機構對 sVNA 滴度或臨床抗體抗病毒活性的信心足夠高，可以使用該替代品作為從一個臨床數據集連接到新分子的一種方式，而無需進行完整的預授權臨床研究，就像我們對準備授權所做的那樣。

From a regulatory perspective, it was clear in 2022 and has been clear for the last three years that EUA was the pathway FDA preferred or believed was the best fit with what was understood to be a short, useful life of all COVID-19 monoclonals. This is, of course, a contrast of vaccines which enjoy full approval and sPLA updates on the basis of similar comparative titers.

從監管角度來看，2022 年就已明確，過去三年也已明確，EUA 是 FDA 首選的途徑，或認為最適合所有 COVID-19 單株抗體的短暫使用壽命。當然，這是在類似比較滴度的基礎上對獲得全面批准的疫苗和 sPLA 更新進行的比較。

Either way, in the spring of 2024, a bridging EUA for treatment seemed to be a structure that might suit both our and FDA's interest sets, depending on the nature of the titer bridge, just as was the case for a prep authorization. The clear desire from the agency throughout has been for what they would consider quote, conservatism, unquote, or the highest possible antiviral titers, and therefore antibody dose to satisfy some of the epistemological limitations of immuno bridging.

無論如何，在 2024 年春季，用於治療的橋接 EUA 似乎是一種可能適合我們和 FDA 的利益的結構，這取決於滴度橋的性質，就像準備授權的情況一樣。該機構自始至終的明確願望是，他們認為“保守主義”，或者說“盡可能高的抗病毒滴度”，因此抗體劑量可以滿足免疫橋接的一些認識論限制。

This is an understandable desire. If you remember that the first job of the agency is assurance or confidence and likely clinical benefit rather than stewardship of a medicine's overall profile. There are, of course, consequences to the degree of assurance required by the agency that takes some careful thought in unpacking, which is where we'll spend some time today.

這是一個可以理解的願望。如果您記得，該機構的首要任務是保證或信心以及可能的臨床益處，而不是對藥物整體狀況的管理。當然，機構所要求的保證程度會產生一些後果，需要仔細考慮才能解決，這也是我們今天要花一些時間去討論的問題。

It is an important exercise in part for reasons embedded into our citizen petition. There is a wide gap between the assumptions and habits of [CBER] and [Sedar] respectively, as between assurances traditionally required of COVID vaccine versus assurances traditionally required for COVID monoclonal antibodies and we believe regulatory evolution is required for the benefit of patients in need.

這是一場重要的活動，部分原因在於我們的公民請願書中所包含的。[CBER] 和 [Sedar] 的假設和習慣之間存在很大差距，就像傳統上對 COVID 疫苗所需的保證與傳統上對 COVID 單株抗體所需的保證之間存在很大差距一樣，我們認為需要進行監管變革以造福有需要的患者。

A few more background points. First, pemivibart and adintrevimab, despite being near identical molecularly, have very different potencies and hence different routes of administration and doses, which means their PK and PD profiles cannot overlap but can be easily compared to one another visually and quantitatively.

還有一些背景要點。首先，pemivibart 和 adintrevimab 儘管在分子上幾乎相同，但效力卻有很大差異，因此給藥途徑和劑量也不同，這意味著它們的 PK 和 PD 特性不能重疊，但可以在視覺和定量上輕鬆相互比較。

Second, the proposal for EUA expansion was for immunocompromised persons for whom alternative therapies are inaccessible or not clinically appropriate, so the choice here is between pemivibart or nothing.

其次，EUA 擴展的提議是針對無法獲得替代療法或臨床上不適用替代療法的免疫功能低下人群，因此這裡的選擇是 pemivibart 或什麼都不做。

Third, we will not touch much on the pemivibart safety profile in this overview, both because pemivibart was and remains authorized for use by people who are well, which would seem to create a safety pathway for use by people who are sick, and because the bulk of FDA feedback relates to the science of assurance of efficacy benefit in immuno bridging.

第三，在本概述中，我們不會過多地涉及 pemivibart 的安全性，因為 pemivibart 過去和現在都被授權供健康人群使用，這似乎為病人使用創造了一條安全途徑，而且 FDA 的大部分反饋都與保證免疫橋接功效的科學有關。

Slide 23. The major FDA finding on the application for treatment presented in terms that are drawn straight from the EUA statute is that they are unable to reasonably conclude that the known and potential benefits of pemivibart in treatment outweigh the known and potential risk. They offered four specific scientific conclusions related to assurance of clinical benefit in the immuno bridging exercise, which we have paraphrased here and will present in more detail on the next slide.

幻燈片 23。FDA 對直接取自 EUA 法規的治療申請的主要發現是，他們無法合理地得出結論，認為 pemivibart 在治療中的已知和潛在益處大於已知和潛在風險。他們提出了四個與免疫橋接練習中的臨床益處保證相關的具體科學結論，我們在這裡對其進行了解釋，並將在下一張幻燈片中更詳細地介紹。

Slide 24 depicts curves and comparison between adintrevimab and pemivibart PK and PD expressed as sVNA titer or clinical antiviral activity, the primary basis for immuno bridging.

幻燈片 24 描繪了 adintrevimab 和 pemivibart PK 和 PD 之間的曲線和比較，以 sVNA 滴度或臨床抗病毒活性表示，這是免疫橋接的主要基礎。

On the upper left chart, you can see that that intrevimab being administered intramuscularly, starts with very low circulating titers and rises slowly over five to seven days toward its peak. By contrast, pemivibart is dosed intravenously and so begins instantly very high and then settles over time.

在左上角的圖表中，您可以看到，肌肉注射的 intrevimab 開始時循環滴度非常低，並在五到七天內緩慢上升至峰值。相較之下，pemivibart 是透過靜脈注射給藥的，因此一開始的劑量會非常高，然後隨著時間的推移而穩定下來。

You can read below the FDA interpretation of the comparative curves, which they describe as quote, similar to or higher than, unquote adintrevimab for only three days, after which it is less than. And you can see a table in the upper right expressing the ratio of those two curves over various increasingly longer time periods. The agency here is justifiably focused on whether pemivibart delivers comparative titers to adintrevimab for the longest possible time.

您可以在下面閱讀 FDA 對比較曲線的解釋，他們將其描述為“類似於或高於”，僅三天就取消引用 adintrevimab，之後它就低於。您可以在右上角看到一個表格，其中顯示了這兩條曲線在各個逐漸延長的時間段內的比率。該機構有理由關注 pemivibart 是否能在最長時間內提供與 adintrevimab 相當的滴度。

Next slide, 25, conveys our perspective on this primary immuno bridging. In contrast to FDA description, we see adintrevimab titers as much higher than, or comparable to adintrevimab for four days, then modestly below for day five, after which the pemivibart titers settle below adintrevimab, but are of course still quite high compared to nothing for many days and then weeks, given the half-life of the molecule. Why are we at Invivyd so interested in five days?

下一張投影片 25 傳達了我們對這種主要免疫橋接的看法。與 FDA 的描述相反，我們發現 adintrevimab 滴度在四天內遠高於或與 adintrevimab 相當，然後在第五天略低於 adintrevimab，之後 pemivibart 滴度穩定在 adintrevimab 以下，但當然，考慮到分子的半衰期，與連續多天沒有滴度甚至相當高數週沒有滴度。為什麼我們 Invivyd 對五天如此感興趣？

Three reasons. First, over five days, adintrevimab conferred the majority of its measured virologic benefit compared to placebo, even starting at very low titers. Second, treatment alternatives, Paxlovid and Lagevrio, are five-day regimens themselves, after which, of course, they stop and confer zero antiviral activity.

有三個原因。首先，在五天內，與安慰劑相比，adintrevimab 表現出了大部分測量到的病毒學益處，即使從非常低的滴度開始也是如此。其次，治療替代方案 Paxlovid 和 Lagevrio 本身就是為期五天的療程，當然，五天之後，它們就會停止，並且不會產生任何抗病毒活性。

And third, as a general statement, treating early in the course of an infection of COVID-19 is associated with improved outcomes. So to us, that five-day duration comparison is rather interesting, and the seven-day comparison is attractive. Although we agree that conferring long-term antiviral activity to help with persistent shedding or viral rebound is a wonderful potential benefit of using long-acting antibodies in a treatment setting.

第三，一般來說，在 COVID-19 感染過程中早期治療可以改善治療效果。因此對我們來說，五天的持續時間比較相當有趣，而七天的比較則很有吸引力。儘管我們同意，賦予長期抗病毒活性以幫助持續脫落或病毒反彈是在治療環境中使用長效抗體的一個很好的潛在好處。

Finally, to us, while an immuno bridging analysis like this one compares a predicate antibody to a new antibody, of course, for patients in need today, the actual choice in front of FDA is between the new antibody and nothing at all, to which we will return in a moment.

最後，對我們來說，雖然像這樣的免疫橋接分析將謂詞抗體與新抗體進行了比較，當然，對於今天有需要的患者來說，FDA 面臨的實際選擇是在新抗體和什麼都不做之間，我們稍後會回到這個問題。

Slide 26, next slide, depicts one of two conceptually and substantively similar meta-analysis presented to the agency. In this case, you can see that pemivibart is not among the most potent antibodies ever developed for COVID-19, which we understand and agree with. It is, however, well within the range of effective mab titers and would provide antiviral activity a good bit above sotrovimab used to treat COVID-19 to great effect in the pandemic phase of COVID-19.

下一張投影片 26 展示了向該機構呈現的兩個概念上和實質上相似的統合分析之一。在這種情況下，您可以看到 pemivibart 並不是迄今為止針對 COVID-19 開發的最有效的抗體之一，我們理解並同意這一點。然而，它完全在有效單株抗體滴度範圍內，並且提供的抗病毒活性遠高於用於治療 COVID-19 的索曲馬單抗，在 COVID-19 大流行階段效果顯著。

Also on this chart, on the right side, -- excuse me, the left side of the curve, you will see convalescent plasma titers. Convalescent plasma, interestingly enough, retains a treatment EUA, and you can see that the range of antiviral activity conferred by convalescent plasma is far below both sotrovimab and pemivibart. Nonetheless, the FDA notes here that they would wish pemivibart to be nudged more to the right to sit among other mabs, irrespective of the fact that moving rightward appears to have a de minimis predictive effect on expected clinical outcomes.

另外，在這張圖表的右側——對不起，是曲線的左側，你會看到恢復期血漿滴度。有趣的是，恢復期血漿保留了治療 EUA，您可以看到恢復期血漿給予的抗病毒活性範圍遠低於 sotrovimab 和 pemivibart。儘管如此，FDA 在此指出，他們希望將 pemivibart 移到更右側，與其他單株抗體放在一起，而不管向右移動似乎對預期的臨床結果具有微不足道的預測作用。

Slide 27 presents our view on this point. Moving rightward may confer some benefit to patients, and we may be able to do it with newer molecules. But alas, we are once again not picking between all of these molecules as if any of the comparators currently exist. The only active molecules depicted on this chart are pemivibart and the components of convalescent plasma well to the left.

投影片 27 展示了我們對這一點的看法。向右移動可能會給患者帶來一些好處，我們也許能夠利用更新的分子來實現這一點。但遺憾的是，我們再次沒有在所有這些分子之間進行選擇，就好像任何比較器目前存在一樣。此圖表上描繪的唯一活性分子是 pemivibart 和左側的恢復期血漿成分。

Further, agency leadership was well aware and communicated to us in the past that antibodies have been consistently overdosed, which seems like a minor, maybe even academic problem, until now when a decision has to be made about an antibody like pemivibart. We look at the activity conferred pemivibart and see it as well in an antiviral range validated by RCT as having an attractive treatment effect.

此外，機構領導層非常清楚，並且在過去向我們傳達了抗體持續過量使用的情況，這似乎是一個小問題，甚至是學術問題，直到現在必須對 pemivibart 等抗體做出決定。我們研究了 pemivibart 所賦予的活性，並發現它在 RCT 驗證的抗病毒範圍內具有良好的治療效果。

Slide 28 is the FDA language describing the residual clinical uncertainty of what pemivibart dose may be optimal for those severely immune-compromised patients who are fighting an active infection without adequate immunologic response.

幻燈片 28 是 FDA 的語言，描述了對於那些在沒有足夠免疫反應的情況下對抗活動性感染的嚴重免疫缺陷患者來說，pemivibart 劑量可能是最佳的剩餘臨床不確定性。

On slide 29, we simply note on this point, there is a peculiar and deeply unfortunate consequence to the FDA's perspective for patients in such clear need.

在第 29 張投影片上，我們只是簡單地指出了這一點，對於有如此明顯需要的患者來說，FDA 的觀點會帶來特殊且非常不幸的後果。

Slide 30 relates to the fact that indeed comparative antibodies are different and may have subtle differences in mechanism of action, and those differences may be difficult to measure but weigh on regulatory consideration.

幻燈片 30 涉及這樣一個事實，即比較抗體確實是不同的，並且在作用機制上可能有細微的差別，這些差別可能難以衡量，但對監管考慮有影響。

Slide 31, next, notes our view that indeed other than neutralization activity, we assessed and found a vector function essentially identical between pemivibart and adintrevimab, which should not be a surprise given the identical backbones.

接下來的幻燈片 31 指出了我們的觀點，即除了中和活性之外，我們評估並發現 pemivibart 和 adintrevimab 之間的載體功能基本上相同，考慮到相同的骨架，這並不奇怪。

As for antibody non-neutralization, non-effector activities that are undescribed and unmeasured by both industry and FDA, those are a little hard for us to assess and respond to. We would humbly submit that these ambiguities are ever present in medicines new and old and indeed, we would welcome guidance on what unknown and undescribed thing we might measure going forward.

至於抗體的非中和作用、非效應活性，行業和 FDA 都未描述和測量，這對我們來說有點難以評估和應對。我們謙虛地認為，這些模糊性在新舊藥物中始終存在，事實上，我們歡迎有關我們未來可能測量哪些未知和未描述的東西的指導。

So slide 32, where are we? Well, we have a new leadership team at the FDA, a changing agency, and as described, changing priorities at FDA and HHS. We intend to continue engagement with FDA both on pemivibart, which is here today, and on our new molecule, VYD2311, which we have accelerated rapidly through early clinical development. As a final point on the matter, slide 33 depicts the result of a similar analysis for bridging to treatment.

那麼投影片 32，我們在哪裡？嗯，FDA 有一個新的領導團隊，一個正在改變的機構，而且正如所描述的，FDA 和 HHS 的優先事項也在改變。我們打算繼續與 FDA 合作，無論是今天推出的 pemivibart 還是我們已透過早期臨床開發迅速加速的新分子 VYD2311。作為這個問題的最後一點，幻燈片 33 描述了對橋接治療的類似分析的結果。

For VYD2311, using arithmetic from currently circulating variants. You can see on the Y-axis that both proposed doses of VYD2311 provide sVNA tighter well in excess to that adintrevimab and indeed can either approach from below or well exceed the titers delivered by Regen-Cov, which sat toward the top of the old antibody leaderboard if you're keeping score at home.

對於 VYD2311，使用當前流通變體的演算法。您可以在 Y 軸上看到，兩種建議劑量的 VYD2311 都提供了比 adintrevimab 更緊密的 sVNA，並且確實可以從下方接近或遠遠超過 Regen-Cov 提供的滴度，如果您在家記分，Regen-Cov 位於舊抗體排行榜的頂部。

With data like these for VYD2311, we see the majority of the agency's pemivibart concerns well addressed. We hope that this comparison and recitation of the pemivibart treatment declination logic answers outstanding questions in the field. We will be working up a manuscript to describe the situation for a scientific journal in the next weeks.

有了 VYD2311 的這些數據，我們發現該機構對 pemivibart 的大部分擔憂都得到了很好的解決。我們希望對 pemivibart 治療拒絕邏輯的比較和敘述能夠回答該領域的突出問題。我們將在接下來的幾週內撰寫一份稿件，為科學期刊描述這種情況。

In the biggest picture, we're thrilled with the medical potential we see in our medicines. We appreciate the FDA's alignment with our desire for greater public transparency, and we look forward to re-engaging with the new FDA to discuss pemivibart, VYD2311, and this field of medicine generally.

從總體上看，我們對我們的藥物的醫療潛力感到非常興奮。我們感謝 FDA 認同我們對提高公眾透明度的渴望，我們期待與新 FDA 重新合作，討論 pemivibart、VYD2311 以及整個醫學領域。

Needless to say, it is our overarching goal as a company to bring important high-value medicines to patients in need as rapidly as possible.

毋庸置疑，作為一家公司，我們的首要目標是盡快為有需要的患者提供重要的高價值藥物。

I'll now turn the call over to Bill Duke to talk about the financials before we move to Q&A. Bill?

在我們進入問答環節之前，我現在將把電話轉給比爾杜克 (Bill Duke) 來討論財務狀況。帳單？

Thank you, Marc. Turning to slide 35, prior to today's call, we released our Q1 2025 results, including PEMGARDA net product revenue of $11.3 million in March, ending cash and cash equivalent of approximately $48 million.

謝謝你，馬克。翻到第 35 張投影片，在今天的電話會議之前，我們發布了 2025 年第一季的業績，包括 3 月 PEMGARDA 淨產品收入 1,130 萬美元，期末現金和現金等價物約為 4,800 萬美元。

As previously mentioned, to drive long-term top line growth, we made a strategic decision to internalize our sales force at the beginning of 2025. Although the shifts created a short-term headwind reflected in PEMGARDA products revenue during Q1, we are now seeing positive momentum with the return to growth and early signs of acceleration in Q2.

如前所述，為了推動長期營收成長，我們做出了策略決策，在 2025 年初將銷售團隊內部化。儘管這些轉變在第一季對 PEMGARDA 產品收入造成了短期不利影響，但我們現在看到了積極的勢頭，第二季度恢復了成長並出現了加速的早期跡象。

We are pleased with the continued execution of financial discipline, reporting a continued reduction of operating expenses. We reported $27.4 million in operating expenses in Q1 2025 compared to $32.3 million in Q4 2024, a 15% reduction of quarter over quarter.

我們很高興看到財務紀律的持續執行，營運費用持續減少。我們報告 2025 年第一季的營運費用為 2,740 萬美元，而 2024 年第四季的營運費用為 3,230 萬美元，較上季減少 15%。

This was after a decrease from Q3 to Q4 of over 50%. We anticipate operating expenses will continue to decrease in the second quarter as we have manufactured sufficient supply of PEMGARDA and VYD2311 and do not plan for significant further manufacturing expense in the near term.

這是繼第三季至第四季下降超過 50% 之後的另一個下降。我們預計第二季營運費用將繼續下降，因為我們已經生產了足夠的 PEMGARDA 和 VYD2311 供應，短期內不打算進一步大幅增加製造費用。

Backed by a strong cash position and potential to access up to $30 million in non-diluted funding through our term loan facility with SVB secured in April, we remain focused on growing PEMGARDA topline revenue, continued financial discipline and continue to target profitability by the end of the first half of 2025.

憑藉強大的現金狀況和透過 4 月與 SVB 達成的定期貸款協議獲得高達 3000 萬美元非稀釋資金的潛力，我們將繼續專注於增加 PEMGARDA 的營業收入、保持財務紀律，並繼續以 2025 年上半年末實現盈利為目標。

I'll now turn the call over to the operator to open the call for questions.

我現在將把電話轉給接線員，開始提問。

Thank you. (Operator Instructions) Michael Yee, Jeffreys.

謝謝。（操作員指示）Michael Yee，Jeffreys。

Hey, good morning, guys. Thanks for taking our questions. This is Kyle Yang from Michael. Just a few from us. The first one is, could you please characterize your recent interaction and/or experience with the new agency, particularly on EUA, including maintaining your EUA for COVID prevention and use of EUA for future applications including for treatment and also use of surrogate endpoints such as virus titers for approval?

嘿，大家早安。感謝您回答我們的問題。我是 Michael 的 Kyle Yang。我們只有幾個。第一個問題是，您能否描述您最近與新機構的互動和/或經驗，特別是在 EUA 方面，包括維持用於 COVID 預防的 EUA 以及將 EUA 用於未來的應用（包括治療）以及使用病毒滴度等替代終點進行批准？

The second one real quick is on Q1 sales. Could you please cha characterize your -- the headwinds that you encountered in Q1. I understand you -- team briefly discussed it. Could you please expand on that and tell us how you addressed these areas of improvements in the second quarter and just help us think about your sales in Q2 and how do you -- and your confidence -- why -- what gives you confidence that you're going to see the momentum continue in the second quarter? Thank you.

第二個是關於第一季的銷售情況。您能否描述一下您在第一季遇到的阻力？我理解你的意思——團隊對此進行了簡短的討論。您能否詳細說明一下，並告訴我們您在第二季度如何解決這些改進領域，並幫助我們思考您在第二季度的銷售情況，以及您如何 - 以及您的信心 - 為什麼 - 是什麼讓您有信心看到這種勢頭在第二季度繼續保持？謝謝。

Great, thanks so much. Let me start and then I'll ask Tim to answer the second part. So regarding EUA, you asked a couple of different things but with respect to maintenance of the EUA, it is actually our preference to move with the FDA beyond that construct.

太好了，非常感謝。讓我先開始，然後我會請提姆回答第二部分。因此，關於 EUA，您問了幾個不同的問題，但就 EUA 的維護而言，我們實際上更傾向於與 FDA 一起超越這一構想。

Indeed, it's generally understood that EUAs are designed to effectively convert at some pace and subject to some mechanism. We've not actually had that conversation with the new FDA, which, as you may or may not know, is effectively recently seeded, but we're looking forward to it very much. Critically, our current EUA for the prevention of COVID-19 in certain immunocompromised persons, yeah, was generated on the basis of immuno bridging, but of course carries with it the results of a randomized clinical study interrogating both safety and exploratory clinical efficacy. So in our minds, those data are unique in the field.

事實上，人們普遍認為 EUA 的設計目的是以一定的速度並遵循某種機制進行有效轉換。我們實際上還沒有與新的 FDA 進行過這樣的對話，您可能知道也可能不知道，它實際上是最近才成立的，但我們非常期待。至關重要的是，我們目前針對某些免疫功能低下人群預防 COVID-19 的 EUA 是在免疫橋接的基礎上產生的，但當然也帶有隨機臨床研究的結果，該研究既考察了安全性，也考察了探索性臨床療效。所以在我們看來，這些數據在該領域是獨一無二的。

This is the point we've raised in a few different domains, particularly our recent Citizen Petition. So, unlike any other company we're aware of that has an authorized preventative or approved preventative, we actually have contemporary efficacy data. And so would seek to leverage that in one form or another, subject to discussion with the FDA of moving towards BLA. That would be our preference, and it would certainly be our preference going forward. So I don't think any of that is either of -- nerve-wracking nor surprising, it's in fact embedded into the very nature of a grant to the EUA and we're really looking forward to talking with them about that.

這是我們在幾個不同領域提出的觀點，特別是我們最近的公民請願。因此，與我們所知的任何其他擁有授權預防措施或批准預防措施的公司不同，我們實際上擁有當代的功效數據。因此，將尋求以某種形式利用這一點，但要與 FDA 討論轉向 BLA。這是我們的偏好，也肯定也是我們未來的偏好。因此，我認為這些都不是令人緊張或驚訝的事情，事實上，它已經融入到對 EUA 的資助的本質中，我們非常期待與他們討論這個問題。

On a go-forward basis, I think what we see is a pretty clear scientific, and I mean, sort of academic and clinical understanding that sVNA titers are a highly useful validated surrogate endpoint. And you can see that embedded into, of course, the work that we've done with FDA to date. And in fact, the evolution of our product fact sheet, which alludes to some of the meta-analytics describing these relationships.

從未來來看，我認為我們看到的是一種相當清晰的科學依據，我的意思是，從某種學術和臨床角度來理解，sVNA 滴度是一種非常有用的、經過驗證的替代終點。當然，您可以看到這一點已經融入我們迄今為止與 FDA 合作開展的工作中。事實上，我們的產品說明書的演變，暗示了一些描述這些關係的統合分析。

So we see the endemic virus situation as an opportunity to normalize all of this away from EUA into a landscape akin to an accelerated approval with the postmarket conversion study, which I think not coincidentally perhaps, appears to be the direction of travel for COVID-19 vaccines.

因此，我們將地方性病毒疫情視為一個機會，使這一切從 EUA 正常化，進入類似於透過上市後轉化研究加速批准的局面，我認為這也許並非巧合，這似乎是 COVID-19 疫苗的發展方向。

All of that is to us highly welcome and embedded into all of our plans for both pemivibart and our molecules going forward. You have to remember that an EUA does not carry an express obligation to generate randomized clinical data on the other side of it. But of course, acceleratedated approvals do. So we would look forward to that paradigm and it's going to be a major feature of what we believe will be our upcoming discussions with the agency.

我們非常歡迎這一切，並將其融入我們未來對 pemivibart 和分子的所有計劃中。您必須記住，EUA 並不承擔在其另一側產生隨機臨床數據的明確義務。但當然，加速審批確實如此。因此，我們期待這種模式，我們相信它將成為我們即將與該機構進行的討論的一個主要特徵。

So I hope that's clear. If it's not, please get back into the queue. But meanwhile, I'll ask Tim to expand on our Q1 changes and our confidence going forward.

我希望這一點很清楚。如果不是，請回到佇列。但同時，我會要求蒂姆詳細說明我們第一季的變化以及我們對未來的信心。

Yeah, of course. Thank you, Marc. I think we - I brushed over it pretty quickly, but when I looked back at what we were able to do in Q1, it was pretty remarkable. We decoupled from the contract sales organization and built our own best in class sales team, trained them and deployed them by partnering with our human resource team to make all this happen in weeks.

是的，當然。謝謝你，馬克。我認為我們 - 我很快就瀏覽了它，但是當我回顧我們在第一季所做的事情時，這是非常了不起的。我們脫離了合約銷售組織，建立了我們自己一流的銷售團隊，透過與我們的人力資源團隊合作對他們進行培訓和部署，在幾週內完成了這一切。

And so we did see a disruption in field activity. But with that, we were really thoughtful on how we made that approach and amplified some of our -- some of the air cover that we can do with digital marketing, and others to fill a little bit of that void.

因此我們確實看到了現場活動的中斷。但同時，我們確實認真考慮瞭如何採取這種方法，並擴大了我們的一些範圍——一些我們可以透過數位行銷進行的空中掩護，以及其他一些可以填補一點空白的方法。

I think what we're pleased with seeing right now, and I shared it on the key launch metrics slide is that when you look from January 1 through the end of April 30, we're seeing a really nice increase in breadth, depth, as well as unique accounts that the team is calling on. So we've really refocused around what we're calling, a core for specialists, including rheumatology, where we've seen a high degree of acceptance and adoption. And it's been a really good area of focus for us. I also look at where PEMGARDA is available.

我認為我們現在很高興看到這一點，而且我在關鍵發布指標幻燈片上也分享了這一點，當你回顧從 1 月 1 日到 4 月 30 月底的情況時，我們看到團隊所呼叫的廣度、深度以及唯一帳戶都有了非常好的增長。因此，我們確實重新關注了我們所謂的專家核心，包括風濕病學，我們已經看到了高度的接受度和採用度。這對我們來說是一個非常值得關注的領域。我也會查看哪裡可以買到 PEMGARDA。

When I had my first call about a year ago with you, we had about 120 sites. Right now, if you go to our Infusion Finder, we have over 880 sites. So we continue to drive access to PEMGARDA really broadly through multiple channels and are starting to see that. Aand as I alluded to, we're seeing some really strong numbers into Q1 right now and are excited about that.

大約一年前，當我第一次與您通話時，我們有大約 120 個站點。現在，如果您造訪我們的輸液查找器，我們有超過 880 個站點。因此，我們繼續透過多種管道廣泛推動 PEMGARDA 的普及，並且開始看到這一點。正如我所提到的，我們現在看到第一季的一些非常強勁的數據，對此我們感到興奮。

Thanks so much.

非常感謝。

Patrick Trucchio, HC Wainwright. (Operator Instructions)

派崔克·特魯基奧、HC·溫賴特。（操作員指示）

Hi, good morning. I'm sorry I was on mute. This is Luis in for Patrick. Thank you for taking our questions. And again, we understand that there are -- these are challenging times which we appreciate all of the team's work and progress so far. So on a follow-up question a little bit to what we discussed earlier, can you discuss a little bit more in detail the measles program, if you plan to pivot (technical difficulty) measles and if you -- what -- every details you can share on the expected clinical trial development path and potential market size and how -- and in the context of your current cash position and the non-diluted loan facility, how you're planning to prioritize?

嗨，早安。抱歉，我靜音了。這是路易斯代替派崔克。感謝您回答我們的問題。我們再次強調，我們理解這是一個充滿挑戰的時期，我們感謝團隊迄今為止所做的所有工作和取得的進展。因此，對於我們之前討論過的後續問題，您能否更詳細地討論一下麻疹計劃，您是否計劃轉向（技術難度）麻疹，以及如果您 - 什麼 - 您可以分享有關預期臨床試驗發展路徑和潛在市場規模的所有細節以及如何 - 以及在您目前的現金狀況和非稀釋貸款額度的背景下，您計劃如何確定優先事項？

Thank you. Yeah, let me start. This is Marc and I'll see maybe Robbie can add some color. But when we're discussing our discovery programs, that is spending that is essentially in all of our standing budgets and it doesn't represent a particularly incremental draw from our forecasted cash balances. It is a matter of priority.

謝謝。是的，讓我開始吧。這是馬克，我看看羅比是否可以添加一些顏色。但是，當我們討論我們的發現計劃時，這些支出基本上都在我們所有的常設預算中，並且並不代表我們預測的現金餘額的特別增加。這是一個優先事項。

So yeah, we're adding a program, for example, in measles, but I want to say you might have used the word pivot, which is not something that I would agree with. We're not pivoting any more than when we leave English class and go to math class, we're pivoting and deciding to just focus on math. We're adding something that we think could be potentially important and that could create a lot of value for patients in need and shareholders over time.

是的，我們正在增加一個項目，例如針對麻疹的項目，但我想說你可能使用了「樞軸」這個詞，而我並不同意這種說法。我們不會再改變方向，就像我們離開英文課去上數學課一樣，我們只是決定專注於數學。我們正在添加一些我們認為可能非常重要的東西，這些東西隨著時間的推移可以為有需要的患者和股東創造很多價值。

So doing these early discovery programs provides us with a basis for considering clinical development under the right circumstances and again, as stewards of capital, we are always going to try to be disciplined about spending shareholder money only on those projects that we see having a very, very attractive near-term return profile.

因此，進行這些早期發現計畫為我們提供了在適當情況下考慮臨床開發的基礎，並且作為資本的管理者，我們始終會努力遵守紀律，只將股東的錢花在那些我們認為具有非常非常有吸引力的短期回報的項目上。

Now, in the case of measles, there may well be some interest in the -- at the -- even the national level, and we will look forward to exploring that potential. But I don't think you can consider any of it as a change or a particular draw on our capabilities or interests elsewhere, it is all about adding optionality and setting into place the ability to grow over the long term both in terms of our -- the scale of our business, but more importantly, growing the scale of our anticipated medical impact.

現在，就麻疹而言，人們可能在——甚至是國家層面——都對此感興趣，我們期待探索這種潛力。但我不認為這其中有任何變化或對我們在其他地方的能力或利益的特別吸引，這一切都是為了增加可選性，並建立長期增長的能力，不僅在我們的業務規模方面，更重要的是，擴大我們預期的醫療影響規模。

Is that clear?

清楚了嗎？

Yeah, that's helpful.

是的，這很有幫助。

Thank you. I would now like to turn the conference back over to the company for any closing remarks.

謝謝。現在，我想將會議交還給公司，以便發表結束語。

Okay. Well, thank you very much all for joining us this morning and we will look forward to any further questions in a follow up later today. Thanks all. Bye-bye.

好的。好吧，非常感謝大家今天早上加入我們，我們期待在今天晚些時候的後續活動中提出任何進一步的問題。謝謝大家。再見。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。