Invivyd Inc (IVVD) 2024 Q3 法說會逐字稿

Good day and thank you for standing by. Welcome to the Q3 2024 Invivyd earnings conference call (Operator Instructions) Please be advised that today's conference is being recorded.

您好，感謝您的支持。歡迎參加 2024 年第三季 Invivyd 收益電話會議（操作員指示）請注意，今天的會議正在錄音。

I would now like to hand the conference over to your speaker today, Katie Falzone, Senior Vice President of Finance. Please go ahead.

現在，我想將會議交給今天的發言人、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 Q3 2024 financial results and recent 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 and Presentations sections respectively.

謝謝您，接線生。不久前，我們發布了一份新聞稿，宣布了我們的 2024 年第三季財務業績和近期業務亮點。新聞稿和今天網路廣播中使用的幻燈片可分別在 Invivyd 網站的「投資者」部分的「新聞稿」和「活動和簡報」部分找到。

Today's discussion will be led by Marc Elia, Chairman of Invivyd Board of Directors and Chairman of the Executive Committee of the Board. He is joined by Tim Lee, Chief Commercial Officer; Will Duke, Chief Financial Officer; Dr. Robert Allen, Chief Scientific Officer; and Dr. Mark Wingertzahn, Senior Vice President of Clinical Development and Medical Affairs.

今天的討論將由 Invivyd 董事會主席兼董事會執行委員會主席 Marc Elia 主持。與他一同出席的還有首席商務官 Tim Lee；威爾·杜克（Will Duke），財務長；羅伯特艾倫博士，首席科學官；以及臨床開發和醫療事務資深副總裁 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 guidance, 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、某些財務指導、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.

這些前瞻性陳述屬於《私人證券訴訟改革法》的規定範圍，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有重大差異。

These forward-looking statements speak only as of the date of this call and Invivyd assumes no duty to update such statements. Additional information on the risk factors that could affect Invivyd's business can be found in our filings made with the US Securities and Exchange Commission, including our most recent Form 10-K and 10-Q, which are also available on our website.

這些前瞻性聲明僅代表本次電話會議之日的觀點，Invivyd 不承擔更新此類陳述的義務。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查閱。

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 for joining us. The third quarter at Invivyd was marked by a promising start and then an unusual commercial headwind that Invivyd has been managing through since. This headwind is rooted in the academic virology complex, the US FDA and unfortunately, as a result, reached HCPs and vulnerable populations that can benefit from more protection from symptomatic COVID-19.

早安，感謝您加入我們。Invivyd 第三季開局良好，但隨後遭遇了不同尋常的商業逆風，Invivyd 一直在努力克服。這種逆風的根源在於學術病毒學綜合體和美國 FDA，不幸的是，其結果也影響到了可以從更多保護中受益的 HCP 和脆弱人群，使他們免受有症狀的 COVID-19 感染。

As a reminder, Invivyd has discovered, developed and is now commercializing a monoclonal antibody against SARS-CoV-2. This virus is now in its endemic phase, following a pandemic that raged through the immunologically naive human population, but now in its endemic phase, still causes a shocking quantity of death, illness and long-term damage, even among the young and healthy.

提醒一下，Invivyd 已經發現、開發並正在商業化一種針對 SARS-CoV-2 的單株抗體。這種病毒曾在免疫學上幼稚的人類群體中肆虐，目前已處於地方性流行階段，但仍在造成大量死亡、疾病和長期損害，甚至在年輕和健康人群中也是如此。

While the backbone of population health for COVID-19 remains vaccine boosts, contemporary data from CDC very consistently reveals the limitations of vaccine boost in terms of the level of protective efficacy a boost can achieve in a human already experienced immunologically from prior vaccination or infection. These limits are universal among humans, although the immunocompromised population, who may receive less benefit due to an inadequate immune response to vaccines, are more variable -- are more vulnerable and bear an even greater burden requiring additional protection.

儘管COVID-19 族群健康的支柱仍然是疫苗加強接種，但來自CDC 的當代數據非常一致地揭示了疫苗加強接種的局限性，即對於已經從先前接種疫苗或感染中產生免疫力的人類，疫苗加強接種可以達到的保護效果水準。這些限制在人類中是普遍存在的，但免疫功能低下的人群由於對疫苗的免疫反應不足而可能獲得較少的益處，他們的情況更加多變、更加脆弱，需要承受更大的負擔，需要額外的保護。

Fortunately, Invivyd has conducted randomized clinical studies on monoclonal antibodies in both the pandemic phase and now the modern endemic phase of SARS-CoV-2 and the results are unambiguous. A monoclonal antibody can render a major step-change in protective efficacy against symptomatic COVID-19 compared to placebo.

幸運的是，Invivyd 在 SARS-CoV-2 大流行階段和現在的現代流行階段對單株抗體進行了隨機臨床研究，結果是明確的。與安慰劑相比，單株抗體可顯著提高對有症狀的 COVID-19 的保護效果。

Unlike modern vaccine-boost epidemiologic studies which reveal about a 40% to 50% reduction in the likelihood of a COVID-19-related hospital stay or urgent care visit for about 60 days, after which benefit fades rapidly, exploratory efficacy data on pemivibart from our CANOPY Phase 3 clinical trial, demonstrated in an immunocompetent population an 80% to 90% reduction in the risk of getting symptomatic COVID-19 in the first place, over twice dosing during a six-month period. Invivyd recently shared long-term follow-up data from CANOPY showing that indeed robust protection remains even at low residual drug levels after six months following cessation of dosing, consistent with prior publications and indeed consistent with our overall corporate thesis for scaled monoclonal antibody protection at potential low doses and via attractive routes of administration.

現代疫苗加強流行病學研究表明，在約 60 天內，與 COVID-19 相關的住院或緊急護理就診的可能性降低了約 40% 至 50%，之後益處迅速消退，而來自我們的CANOPY 第三階段臨床試驗證明，在免疫功能正常的人群中，在六個月內兩次給藥可將出現症狀的COVID-19 的風險降低80% 至90%。Invivyd 最近分享了CANOPY 的長期追蹤數據，該數據表明，即使在停止用藥六個月後，藥物殘留水平較低，仍能提供強有力的保護，這與先前發表的研究結果一致，也符合我們關於單株抗體規模化保護的整體公司論點。

Against this backdrop remains SARS-CoV-2 virus genetic variation, a source of fascination and consternation for the academic and regulatory communities and a major focus of our work internally at Invivyd. SARS-CoV-2 has displayed remarkable genetic mutability and there exists a substantial cottage industry devoted to describing and considering those mutations. From Invivyd's point of view, as a pharmaceutical company, variation is why we have made a major investment in technology designed to understand and address that variation and why we select the molecules we select, with barriers to resistance in mind.

在此背景下，SARS-CoV-2 病毒基因變異仍然存在，這是學術界和監管界著迷和擔憂的原因，也是我們 Invivyd 內部工作的重點。SARS-CoV-2 表現出顯著的基因可變性，並且有大量家庭手工業致力於描述和研究這些突變。從 Invivyd 的角度來看，作為一家製藥公司，變異是我們在旨在理解和解決這種變異的技術上進行大量投資的原因，也是我們在選擇分子時考慮到抗藥性障礙的原因。

We're all incredibly proud that so far, Invivyd stands alone in both attempting and accomplishing this goal in the contemporary context of a post-Omicron era, utilizing rapid approval pathways in concert with FDA. Pemivibart's longstanding and continued antiviral activity to-date is a remarkable scientific accomplishment and one we are eager to repeat with an improved drug profile. Alas, applied virology is an inexact science, all the more inexact outside of an industrial, highly controlled context. And there are many labs globally that seek to understand our molecules using processes and systems of unknown quality and reagents of unknown characteristic.

我們都非常自豪，到目前為止，Invivyd 在後 Omicron 時代的當代背景下獨自嘗試並實現了這一目標，並與 FDA 合作利用快速審批途徑。Pemivibart 迄今為止的長期持續抗病毒活性是一項了不起的科學成就，我們渴望透過改進的藥物特性來重複這一成就。可惜，應用病毒學是一門不精確的科學，在工業和高度控制的環境之外就更加不精確了。全球有許多實驗室試圖使用品質未知的流程和系統以及特性未知的試劑來了解我們的分子。

One of those systems in labs has presented an unusual headwind that cast doubt on the activity of our molecule against contemporary lineages, notably KP.3.1.1 observations made at Columbia University over the summer and into the fall. That KP.3.1.1 susceptibility doubt made its way into the US FDA and disappointingly, the agency broadcast that doubt into the HCP and vulnerable populations via not just factsheet updates but also email blast and tweet or whatever tweets are called now. While the PEMGARDA factsheet was corrected in late September with robust neutralization data, generated through Invivyd's industrial virology effort, Invivyd's opportunity to drive utilization in the late third quarter and into the fourth quarter infectious disease season was badly damaged.

實驗室中的一個系統出現了不同尋常的逆風，使人們對我們的分子針對當代譜系的活性產生了懷疑，尤其是今年夏天和秋天哥倫比亞大學對 KP.3.1.1 的觀測。KP.3.1.1 易感性的疑慮進入了美國FDA，令人失望的是，該機構不僅通過情況說明書更新，還通過電子郵件和推文或任何現在所謂的推文，向HCP 和脆弱人群傳播了這種疑慮。儘管PEMGARDA 情況說明書在9 月下旬透過Invivyd 的工業病毒學研究產生的強有力的中和數據進行了更正，但Invivyd 在第三季度末和第四季度傳染病季節推動利用的機會卻受到了嚴重損害。

Invivyd has been seeking to repair this damage in the end market, up to and including news today, in which the New England Journal of Medicine has published not just a letter to the editor from Invivyd, but also a second piece from this laboratory describing their neutralization results against a lab-made antibody, which had to be corrected at the 11th hour by New England Journal, as you can see online. The piece now describes, research-grade pemivibart, which is a critical and sadly late emerge distinction.

Invivyd 一直在尋求修復終端市場的損害，直到今天的新聞中，《新英格蘭醫學雜誌》不僅發表了 Invivyd 的一封致編輯的信，還發表了該實驗室的第二篇文章，描述了他們的針對實驗室製造的抗體的中和結果，必須在最後一刻由《新英格蘭雜誌》進行更正，正如您在網上看到的那樣。作品現在描述了研究級的 pemivibart，這是一個關鍵的但遺憾的是出現較晚的差異。

Prior to the New England Journal of Medicine's correction, it was implied that authentic pemivibart, manufactured by Invivyd, was used in these systems. Invivyd is a science-based company and therefore has a deep respect for the scientific process, but we are also in the business of trying to save lives and believe that the researchers and regulators considering scientific claims ought to exert real caution in making claims about authorized medicines for human use on the basis of rapidly emerging science that may lack appropriate rigor and appropriate control.

在《新英格蘭醫學雜誌》做出更正之前，有消息暗示這些系統中使用了由 Invivyd 生產的正宗 pemivibart。Invivyd 是一家以科學為基礎的公司，因此對科學過程深表尊重，但我們也致力於拯救生命，並認為考慮科學聲明的研究人員和監管機構在提出授權聲明時應該非常謹慎基於快速發展的科學而開發的人類用藥可能缺乏適當的嚴謹性和適當的控制。

Meanwhile, Invivyd remains working to drive awareness of a medicine among HCPs that we believe disrupts disease pathogenesis and has been shown to protect vulnerable Americans who are in need of protection against symptomatic COVID-19. Tim Lee, our Chief Commercial Officer, will describe our ongoing efforts and our thinking about building this important category of medicines and our SVP of Clinical Development and Medical Affairs, Mark Wingertzahn will touch on recent CANOPY data that points the way to scaling our work far beyond what we can do with pemivibart as an intravenous medication.

同時，Invivyd 仍在努力提高 HCP 對該藥物的認識，我們認為該藥物會破壞疾病的發病機制，並已被證明可以保護需要預防有症狀的 COVID-19 的弱勢美國人。我們的首席商務官Tim Lee 將介紹我們正在進行的努力以及我們對打造這一重要藥物類別的想法，我們的臨床開發和醫療事務高級副總裁Mark Wingertzahn 將談及最近的CANOPY 數據，這些數據為我們進一步擴大工作指明了方向超出了我們用 pemivibart 作為靜脈注射藥物所能達到的作用。

More generally, our great hope at Invivyd is that these recent events, our strong and consistent data, and upcoming government transition can all present an opportunity for regulators to consider an impressive and growing totality of data that shows quite clearly, one, the test, boost, treat paradigm championed by the current administration as having, ended the pandemic has left behind extraordinary ongoing human misery. Two, monoclonal antibody protection, especially when deployed in the contemporary human population on top of immune experience from vaccination or infection can be a substantial unlock in terms of high levels of protection from symptomatic disease itself.

更廣泛地說，我們Invivyd 最大的希望是，這些最近發生的事件、我們強大而一致的數據以及即將到來的政府過渡，都可以為監管機構提供一個機會，讓他們考慮令人印象深刻且不斷增長的數據，這些數據清楚地表明，一是測試，現任政府所倡導的治療範式雖然結束了這場疫情，但卻留下了持續不斷的極大痛苦。二、單株抗體保護，尤其是在當代人類群體中，在接種疫苗或感染的免疫經驗基礎上加以應用，可以顯著提高對有症狀疾病本身的高水平保護。

Three, protection at low serum virus neutralizing antibody titers has now been demonstrated by monoclonal antibodies in both the pandemic and modern endemic phase of SARS-CoV-2 and such data can be leveraged to make products that would look and feel rather like a vaccine, for example, intramuscular or similarly convenient administration, but which could be distinguished by high efficacy and durable equitable protection, all without forcing human subjects to encounter the SARS-CoV-2 spike protein in vaccine form and experience associated reactogenicity. And four, companies like Invivyd have been and remain prepared to action these initiatives as soon as key governmental stakeholders are ready.

三、單株抗體在SARS-CoV-2 大流行和現代地方性流行階段均已證明，在低血清病毒中和抗體滴度下具有保護作用，可以利用此類數據製造外觀和感覺與疫苗相似的產品，例如肌肉注射或類似便捷的給藥，但其具有高效性和持久的公平保護作用，而不需要強迫人類受試者在疫苗形式中遇到SARS-CoV-2 刺突蛋白並體驗相關的反應原性。第四，一旦主要政府利害關係人做好準備，像 Invivyd 這樣的公司就一直準備好採取這些措施。

Despite the extraordinary recent circumstances surrounding this company and our ongoing PEMGARDA launch, we have been gratified to see a recent return to product growth. We are pleased with the durability of pemivibart and our next generation antibody, VYD2311, in the face of virus variation and we stand prepared to radically scale the impact of our work near-term.

儘管該公司近期正在進行的 PEMGARDA 推出遭遇了特殊情況，但我們很高興看到近期產品成長的恢復。我們對 pemivibart 和我們的下一代抗體 VYD2311 在病毒變異面前的耐用性感到滿意，我們準備在短期內大幅擴大我們工作的影響。

With that, I will turn the call over to Mark Wingertzahn, Senior Vice President of Clinical Development and Medical Affairs.

說完這些，我將把電話轉給臨床開發和醫療事務資深副總裁 Mark Wingertzahn。

Thank you, Marc. If we could turn our attention to slide 6. The efficacy results from the immunocompetent arm from the ongoing 12-month CANOPY study as well as the major COVID-19 variant waves during that time, are depicted on the current slide.

謝謝你，馬克。如果我們可以將注意力轉向第 6 張投影片。目前幻燈片展示了正在進行的為期 12 個月的 CANOPY 研究中免疫功能正常的組別的療效結果以及該期間的主要 COVID-19 變異波。

As you may recall, the CANOPY study is an ongoing 12-month clinical study designed to evaluate safety, tolerability and efficacy of pemivibart for pre-exposure prophylaxis of COVID-19 in adults aged 18 years and older. Participants received two doses of pemivibart infused 90 days apart and then were followed through month 12. The study was conducted from fall 2023 through winter of 2024, making this study one of the few, if only, COVID-19 studies conducted in the contemporary population.

您可能還記得，CANOPY 研究是一項正在進行的為期 12 個月的臨床研究，旨在評估 pemivibart 對 18 歲及以上成年人進行 COVID-19 暴露前預防的安全性、耐受性和有效性。參與者間隔 90 天接受兩劑 pemivibart 輸注，然後進行追蹤至第 12 個月。該研究於 2023 年秋季至 2024 年冬季進行，是少數針對當代人群進行的 COVID-19 研究之一。

Over the entire one-year period, an impressive rate of relative risk reduction from symptomatic COVID-19 was observed with PEMGARDA versus placebo. Strong protection was observed with PEMGARDA over multiple variant waves and lineages of SARS-CoV-2, not only during the active dosing period, but also during the six-month follow-up washout period.

在整個一年的時間裡，與安慰劑相比，PEMGARDA 對有症狀的 COVID-19 的相對風險降低了顯著。PEMGARDA 對 SARS-CoV-2 的多種變異波和譜系均表現出強大的保護作用，不僅在有效給藥期間，而且在六個月的隨訪洗脫期內也是如此。

During the active treatment period, an 84% relative risk reduction from confirmed symptomatic COVID-19 versus placebo was observed in the immunocompetent arm of CANOPY, also known as Cohort B. A substantial degree of protection remained over months 7 to 12 after cessation of drug during a KP.3 and KP.3.1.1 wave with an overall 76% relative risk reduction versus placebo observed in this cohort over the full 12 months.

在積極治療期間，與安慰劑相比，CANOPY 免疫功能正常的組別（也稱為B 組）中觀察到確診有症狀的COVID-19 的相對風險降低了84%。內部仍保持了相當程度的保護在 KP.3 和 KP.3.1.1 波期間，與整個 12 個月內觀察到的安慰劑相比，該群體的總體相對風險降低了 76%。

Reassuringly, the safety profile for pemivibart remained consistent with the PEMGARDA factsheet. The strong protection observed during the washout period is particularly impressive given the low residual titer levels. And while there are no head-to-head trials, we believe that protection can follow from fewer doses of antibody than the doses of vaccine boost that would be required to get protection for immunocompromised persons who are unlikely to mount an adequate immune response to the COVID-19 vaccine.

令人放心的是，pemivibart 的安全性概況與 PEMGARDA 說明書一致。鑑於殘留滴度水平較低，洗脫期觀察到的強大保護尤其令人印象深刻。And while there are no head-to-head trials, we believe that protection can follow from fewer doses of antibody than the doses of vaccine boost that would be required to get protection for immunocompromised persons who are unlikely to mount an adequate immune response to the嚴重特殊傳染性肺炎疫苗.

If we turn our attention to slide 8 and take a look at our pipeline, as you know, we've identified VYD2311 via affinity maturation of pemivibart against XBB lineage viruses, in an effort to improve on the biophysical properties, including in vitro measured potency. Potency improvements in measured IC50s for an antibody can translate directly to lower doses that are required to achieve meaningful levels of sVNA titer, the pharmacodynamic variable that drives protection and efficacy for a COVID-19 antibody. These lower doses may, in turn, allow for the development of routes of administration that are more patient and system-friendly than intravenous approaches.

如果我們把注意力轉向幻燈片 8，看看我們的產品線，如你所知，我們已經透過 pemivibart 對 XBB 譜系病毒的親和力成熟確定了 VYD2311，以努力改善生物物理特性，包括體外測量的效力。抗體測量 IC50 的效力改善可以直接轉化為達到有意義的 sVNA 滴度水平所需的較低劑量，sVNA 滴度是決定 COVID-19 抗體保護和功效的藥效學變數。反過來，這些較低的劑量可能允許開發比靜脈注射方法更適合患者和系統友善的給藥途徑。

The first-in-human study with VYD2311 began at the end of August and is interrogating intravenous, intramuscular, and subcutaneous dosing to provide flexibility and optionality for achieving titers from one antibody, could be suitable for both COVID-19 prevention as well as treatment. We are currently assessing authorization pathways and plan to discuss (technical difficulty) in light of the CANOPY 12-month clinical efficacy and safety data with regulators and look forward to reviewing our progress with VYD2311 at our next earnings call.

VYD2311 的首次人體研究於8 月底開始，正在研究靜脈注射、肌肉注射和皮下注射的方式，以提供靈活性和選擇性，以實現單一抗體的滴度，既適用於COVID-19 的預防，也適用於治療。我們目前正在評估授權途徑，並計劃根據 CANOPY 12 個月臨床療效和安全性數據與監管機構討論（技術難度），並期待在下次財報電話會議上審查我們在 VYD2311 方面的進展。

I will now turn the call over to Tim Lee, our Chief Commercial Officer. Tim?

現在我將把電話轉給我們的首席商務官 Tim Lee。提姆？

Thank you, Mark, and good morning. Turning to slide 10. The third quarter began commercial transformation. It is my first full quarter at Invivyd and I'm excited to share some of the foundational work that we've built to serve the immunocompromised community. I came to Invivyd because of our mission to serve people who are immunocompromised.

謝謝你，馬克，早安。翻到第 10 張投影片。第三季開始商業轉型。這是我在 Invivyd 工作的第一個完整季度，我很高興與大家分享我們為服務免疫功能低下群體所做的一些基礎工作。我來到 Invivyd 是因為我們的使命是為免疫功能低下的人服務。

This community is made up of fighters, people who are battling cancer, people who have received an organ transplant or bone marrow transplant, have a primary immunodeficiency, advanced HIV, and are actively being treated with high-dose corticosteroids. These are all conditions that can lead people to being vulnerable to an opportunistic virus that causes systemic damage and it's why in 2024 approximately every nine minutes, a person in the US dies with COVID-19.

這個社區由戰士、與癌症作鬥爭的人、接受過器官移植或骨髓移植的人、患有原發性免疫缺陷的人、晚期愛滋病毒患者和積極接受高劑量皮質類固醇治療的人組成。所有這些情況都可能導致人們容易感染機會性病毒，從而導致全身性損害，這就是為什麼在 2024 年，大約每九分鐘，美國就會有一人死於 COVID-19。

COVID-19 continues to be the leading cause of hospitalization and death from respiratory infection in the United States. Protecting this community is a noble mission and I'm proud to be a part of it.

COVID-19 仍然是美國呼吸道感染住院和死亡的主要原因。保護這個社區是一項崇高的使命，我很自豪能夠成為其中的一員。

Turning to slide 11. Data from the CDC shows that ICU admissions for all Americans are greater this season than last, clearly demonstrating that COVID continues to have a lasting impact. Turning to slide 12. You can see that COVID can cause systemic damage with no organ system spared from its impact.

翻到第 11 張投影片。美國疾病管制與預防中心的數據顯示，本季所有美國人的加護病房入院人數比上季增加，清楚顯示新冠肺炎疫情仍在產生持久影響。翻到第 12 張投影片。你可以看到，COVID 會造成全身性損害，任何器官系統都無法倖免。

Turning to slide 13. It is with the immunocompromised community in mind that we are building our commercialization plans. We fought through real headwinds through the month of September as the PEMGARDA factsheet was updated to include reference to third-party data that was not reflective of PEMGARDA's continued neutralization activity for the immunocompromised community, as Marc noted. Clinicians and patients more importantly, were confused by these data. Putting this behind us, we have focused on our mission to serve the immunocompromised community at scale.

翻到第 13 張投影片。我們在製定商業化計劃時就考慮到了免疫功能低下的群體。正如馬克所指出的，9 月我們克服了真正的阻力，因為 PEMGARDA 情況說明書進行了更新，引用了第三方數據，而這些數據並不能反映 PEMGARDA 為免疫功能低下群體持續開展的中和活動。更重要的是，臨床醫生和患者對這些數據感到困惑。拋開這些，我們將專注於我們的使命，為免疫功能低下的社區提供大規模服務。

We're partnering with community and independent infusion centers, along with academic centers and integrated delivery networks to increase sites of care for this community. We're developing a digital presence and recently conducted our first speaker program during IDWeek in Los Angeles. We're bringing the sales team from a contract field force to direct hire and believe it's the right decision to serve this community. We believe now is the right time to structure this team and it will better serve our future growth.

我們正在與社區和獨立輸液中心、學術中心和綜合配送網絡合作，以增加社區的護理場所。我們正在拓展數位業務，最近在洛杉磯的 IDWeek 期間開展了我們的第一個演講者計畫。我們將銷售團隊從合約現場隊伍轉變為直接僱用隊伍，並相信這是為這個社區服務的正確決定。我們相信現在是組建這支團隊的最佳時機，它將更好地服務於我們未來的發展。

We're excited to be investing in patient support programs to ensure there's a smooth access for patients who are prescribed PEMGARDA. We're investing in field reimbursement management team and building a federal account team with a focus on immunocompromised veterans and their families. We've also added an inside sales team with a focus on rheumatology and are impressed by the early results.

我們很高興能夠投資於患者支援計劃，以確保接受 PEMGARDA 治療的患者能夠順利獲得治療。我們正在投資現場報銷管理團隊，並建立一個聯邦帳戶團隊，重點關注免疫功能低下的退伍軍人及其家人。我們還增加了一個專注於風濕病學的內部銷售團隊，早期的結果給我們留下了深刻的印象。

Turning to slide 14. Those actions, along with, as you can see, growth across all launch metrics are positioning us to serve the appropriate immunocompromised community at a larger scale.

翻到第 14 張投影片。如您所見，這些舉措以及所有發布指標的成長，使我們能夠在更大範圍內為適當的免疫功能低下群體提供服務。

With that, I'd like to turn the call over to our Chief Financial Officer, Bill Duke, for final remarks prior to Q&A.

因此，我想將電話轉給我們的財務長比爾杜克 (Bill Duke)，讓他在問答之前發表最後的評論。

Thank you, Tim. Turning to slide 16. As you may have seen at the end of October, we pre-released our Q3 results, including PEMGARDA net product revenue of $9.3 million in Q3 2024 and September ending cash of approximately $107 million, which is consistent with the results reported this morning.

謝謝你，提姆。翻到第 16 張投影片。正如您可能在10 月底看到的那樣，我們預先發布了第三季度業績，包括PEMGARDA 2024 年第三季度的淨產品收入為930 萬美元，9 月底的現金約為1.07 億美元，這與今天上午報告的結果一致。

Further, we noted that we expect to finish 2024 with $65 million or more in cash and cash equivalents. At the same time, we withdrew the guidance of $150 million to $200 million of net product revenue and we guided to earlier this year, citing recent headwind from US FDA late Q3 2024 warning on potential for substantially reduced activity of pemivibart through the PEMGARDA factsheet and other media based on a contested third-party preprint reflecting virologic activity data from a non-pemivibart antibody, as has been noted.

此外，我們指出，預計到 2024 年，我們的現金和現金等價物將達到或超過 6,500 萬美元。同時，我們撤回了1.5 億至2 億美元的淨產品收入預期，並在今年稍早進行了預期，理由是美國FDA 在2024 年第三季末警告稱，pemivibart 的活性可能會透過PEMGARDA 情況說明書大幅降低，這給市場帶來了不利影響。

As Tim mentioned, we are excited about PEMGARDA's potential to reach appropriate immunocompromised patients. As such, we are targeting near-term profitability with existing cash and cash equivalents, anticipated growth of net product revenue in various operational efficiency improvements underway. The good news is that we previously recorded as research and development expense, a significant amount of inventory in preparation for the emergency use authorization submission.

正如蒂姆所說，我們對 PEMGARDA 接觸合適的免疫功能低下患者的潛力感到非常興奮。因此，我們的目標是利用現有現金和現金等價物實現近期盈利，並預計淨產品收入將隨著正在進行的各種營運效率改進而增長。好消息是，我們之前將大量庫存記錄為研發費用，以準備提交緊急使用授權。

As we have managed significant supply of PEMGARDA and do not plan for significant further manufacturing expense in the near term, with continued modest net product revenue growth, we expect that we will turn profitable by the end of June 2025.

由於我們已經管理了大量 PEMGARDA 的供應，並且不打算在短期內進一步大幅增加製造費用，加上淨產品收入持續適度增長，我們預計到 2025 年 6 月底將實現盈利。

I will 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，以便開始提問。

(Operator Instructions) Maxwell Skor, Morgan Stanley.

（操作員指示） 摩根士丹利的 Maxwell Skor。

Great. Thank you, everyone. Could you provide any additional color on the treatment EUA for PEMGARDA, if you've received any feedback from the FDA? And also reason I understand for pulling guidance, but what would give you confidence in providing guidance again? Should we expect it at the end of the year, early next year? If you can walk us through the thought process there, that would be great. Thank you.

偉大的。謝謝大家。如果您收到了 FDA 的任何回饋，您能否提供有關 PEMGARDA 治療 EUA 的更多資訊？我也理解撤回指導的原因，但什麼能讓您有信心再次提供指導呢？我們是否應該期待它在今年年底或明年年初出現？如果您能向我們介紹這個思考過程，那就太好了。謝謝。

Hey, Max, good morning. Why don't I start? This is Marc and then I'll see if anyone from Invivyd wants to chime in. Firstly, on the treatment EUA application, we have been in the process of updating it timely. This is a bridging analysis as defined by the FDA.

嘿，馬克斯，早安。我為何不開始呢？我是馬克，然後我會看看是否有來自 Invivyd 的人願意加入。首先，關於治療 EUA 申請，我們一直在及時更新。這是 FDA 定義的橋接分析。

And so we have taken our opportunities, as our virology has evolved, to update analytics and make sure that those analytics are in front of them. We've not heard anything explicit about it other than, I think, a general statement that the FDA is aware of our perspective on all of these various issues and will be rendering some feedback and thoughts to us on that and a multiple of topics soon. So we shall see and stay tuned.

因此，隨著病毒學的發展，我們抓住機會更新分析方法，並確保這些分析方法始終走在他們前面。我們沒有聽到任何明確的消息，除了一個一般性的聲明，即 FDA 了解我們對所有這些問題的看法，並將很快就此和其他多個主題向我們提供一些反饋和想法。因此我們將會觀察並繼續關注。

On the topic of confidence in guidance, I think, look, it's -- we are forced to project into the future. When we project into the future, we draw heavily on the recent past. And I think if PEMGARDA revenue were to grow in a fashion consistent with the recent past, inclusive of a very, very difficult period in the late summer, early fall, we feel very good about our prospects for meeting that.

關於對指導的信心這個主題，我認為，看，這是──我們被迫投射到未來。當我們展望未來時，我們大量借鏡近期的過去。我認為，如果 PEMGARDA 的收入能夠以與近期一致的方式成長，包括夏末秋初非常困難的時期，我們對實現這一目標的前景感到非常樂觀。

And indeed, of course, it involves two dimensions, right, the rate of revenue growth and our ability to manage our expenses, which is part of what Bill was alluding to. So I think in this case, what we are indexed toward is that the guidance conception doesn't require some bolus as it were of seasonally driven revenue, it would now embrace the simple continuation of trend. So we obviously feel as though we have exited the majority of the period embracing confusion certainly on the activity of pemivibart against KP.3.1.1 and feel good about our ability to drive from here forward.

當然，這確實涉及兩個方面，收入成長率和我們管理費用的能力，這也是比爾所暗示的部分。因此，我認為在這種情況下，我們所關注的是，指導概念不需要像季節性驅動的收入那樣進行一些推動，它現在將包含趨勢的簡單延續。因此，我們顯然感覺到，我們已經走出了對 pemivibart 針對 KP.3.1.1 活性的困惑期，並且對我們今後繼續前進的能力感到很滿意。

And I guess just to add to that, I would ask Tim to comment a little bit on what he has seen over recent weeks.

我想補充一下，我想請蒂姆就最近幾週他所看到的情況發表一些評論。

Yeah. Thank you, Marc. I think we're very pleased with the trend and the growth that we're seeing. And I think that's all in light of the kind of the checklist that I presented of all of the things that we're doing right now up to and including bringing in our sales team, increasing a digital presence and working to increase access at independent infusion centers as well as academic infusion centers and integrated delivery networks. And so I think, as I look at where we are in the activities that we're putting into place right now, very excited about what that will mean.

是的。謝謝你，馬克。我認為我們對所看到的趨勢和成長感到非常滿意。我認為這一切都是基於我所提出的清單，清單上列出了我們現在正在做的所有事情，包括引入我們的銷售團隊、增加數位業務以及努力增加獨立輸液的通路中心以及學術輸液中心和綜合配送網路。因此我認為，當我回顧我們目前正在進行的活動時，我對這將意味著什麼感到非常興奮。

Great. Thank you.

偉大的。謝謝。

Michael Yee, Jeffries.

邁克爾·楊，杰弗里斯。

Hi, good morning. Thanks for the updates. Two questions. On revenue, can you help us understand, while you expect steady growth or growth based on the metrics you're disclosing, are we talking about significant stepwise increases month-over-month? Or are we talking about modest growth?

嗨，早安。感謝您的更新。兩個問題。關於收入，您能否幫助我們理解，雖然您預期收入將穩定成長，或根據您揭露的指標成長，但我們談論的是逐月顯著的逐步成長嗎？還是我們談論的是適度成長？

And to that extent, how does that change in the first quarter and the second quarter? I think there's a perception of seasonality, but maybe you think differently because of the population and whatnot. So help us understand the fourth quarter and then what that looks like in the first and second quarter.

那麼第一季和第二季的情況如何改變呢？我認為存在一種季節性的認知，但也許你會因為人口和其他因素而有不同的想法。因此請幫助我們了解第四季度的情況以及第一季和第二季的情況。

And then on the OpEx, of course, the natural question is that has to change as well in order to hit profitability. So is that expected to be significant declines in R&D over the next few quarters? Because I think what you said was that you don't expect a significant manufacturing campaign. Thank you.

當然，就營運支出而言，自然的問題是，為了實現獲利，營運支出也必須改變。那麼預計未來幾季研發支出將大幅下降嗎？因為我認為您說的是您不期望出現大規模的製造業活動。謝謝。

Hi Mike, good morning. And let me -- I'll ask Tim to comment a little bit more on revenue and Bill on OpEx. But let me just start by saying what you might have read already in our press releases is that we have begun the process already of modifying our base burn. And clearly, those areas on which we will not ever compromise and indeed might allocate incremental spend would be our commercial presence.

嗨，麥克，早安。讓我——我會請蒂姆對收入發表更多評論，並請比爾對營運支出發表更多評論。但首先我想說的是，您可能已經在我們的新聞稿中讀到過，我們已經開始了修改基礎燃燒的過程。顯然，我們永遠不會妥協、甚至可能增加支出的領域是我們的商業存在。

R&D is a topic that has to, by definition, flex with what is occurring with the company clinically. We are coming off of CANOPY spend. We are not yet arriving at a registrational spend for 2311. And as Bill alluded to, in the past, we have expensed manufacturing largely through R&D. So you would have seen organically or rather will -- would see organically anyway some change in our overall burn. We're simply looking to tighten that up and accelerate that reduction in burn.

從定義上來說，研發是一個必須根據公司臨床進展而靈活的主題。我們正在停止 CANOPY 支出。我們尚未確定 2311 的註冊支出。正如比爾所提到的，過去我們主要透過研發來支出製造費用。因此，您會自然而然地看到，或者更確切地說，無論如何都會自然而然地看到我們整體燒錢情況的一些變化。我們只是希望加強這一點並加速減少燒傷。

But why don't I ask Bill to comment a little bit further on that and then turn it over to Tim?

但是我為什麼不請比爾對此做進一步的評論，然後再把它交給蒂姆呢？

Sure. I think Marc highlighted the key points here. With regards to manufacturing spend, of course, we manufactured at risk a significant amount of PEMGARDA prior to EUA and then continued to produce PEMGARDA throughout this year. At this point in time, we have substantially completed the manufacturing runs, and the expenses associated with that, which will not necessarily be repeated as we go forward in 2025. I think that's one of the most significant elements that you can look at from a reduction of spend.

當然。我認為馬克在這裡強調了關鍵點。關於製造支出，當然，我們在 EUA 之前冒險生產了大量 PEMGARDA，然後在今年全年繼續生產 PEMGARDA。目前，我們已經基本完成了生產運作以及相關費用，到 2025 年，我們不一定再重複這些生產運作。我認為這是從減少支出中可以看出的最重要的因素之一。

With regards to 2311, we have also continued -- we have also done manufacturing for 2311 in 2024. Those expenses have flowed through R&D expense for this year as that has not yet been submitted for EUA. So as a result, as that winds down, we will also see relief to the P&L through R&D as we go forward in 2025. Just other streamlined expenses, of course, we are investing heavily in commercial. We will continue to invest on commercial. But that being said, I think the largest thing that you can see is the drop on the R&D expense side.

關於 2311，我們也在繼續——我們也將在 2024 年完成 2311 的製造。由於尚未提交 EUA，這些費用已計入今年的研發費用。因此，隨著這一進程的逐漸結束，到 2025 年，我們也將看到透過研發來緩解損益表的壓力。只是其他精簡的費用，當然，我們在商業方面投入了大量資金。我們將繼續在商業方面進行投資。但話雖如此，我認為最大的變化是研發費用的下降。

Yeah. And great question. I think as we look at our recent activity at IDWeek in Los Angeles in the conversations that we've had with the infectious disease clinicians in their community as well as individual meetings, seasonality is not a construct that I think is something that we're hearing even from some of the largest independent infusion networks across the country, people who serve those fighting cancers and other conditions that I mentioned earlier.

是的。這個問題問得真好。我認為，當我們回顧我們最近在洛杉磯 IDWeek 的活動時，以及我們與社區傳染病臨床醫生的對話以及個人會議時，季節性並不是一個我們甚至聽到全國一些最大的獨立輸液網絡的聲音，這些網路為那些與癌症和我之前提到的其他疾病作鬥爭的人提供服務。

And so as we look at the opportunity to serve this group, right, seasonality doesn't affect those people who are on different therapeutic regimens that will impact their immune system. I think as we look at who our core is, it is people who are fighting for their life because of cancer therapies, because of organ transplant, because of hematopoietic stem cell transplant and others. And those conditions and therapeutic regimens don't know seasonality.

因此，當我們尋找為該群體服務的機會時，季節性不會影響那些接受不同治療方案的人，進而影響他們的免疫系統。我認為，當我們看看我們的核心是誰時，他們就是那些因為癌症治療、器官移植、造血幹細胞移植等而為生命而戰的人。而且這些情況和治療方案與季節無關。

And I think protecting them is what we're gearing up towards. And excited to say from a breadth in account utilization, we're pleased with that. Our opportunity is to drive depth through increased access and that's what the team has been -- one of the many things in the checklist that I went through earlier that the team has been solely focused on is fighting for this community to have access to something that will protect them, as I said, from a virus that is looking to cause systemic damage in heart.

我認為保護他們正是我們正在努力實現的目標。我很高興地說，從帳戶使用的廣度來看，我們對此感到滿意。我們的機會是透過增加訪問權限來推動深度，這就是團隊一直在做的事情——我之前列出的清單中的許多事情之一就是團隊一直專注於為這個社區爭取訪問權限正如我所說的，它將保護他們免受試圖對心臟造成系統性損害的病毒的侵害。

It's probably worth my adding, Mike, just for the clarification of all of our vocabulary, right? We use terms like seasonal because there is a perception in the HCP community that infectious disease and certainly respiratory infectious diseases have a, quote, season, unquote, and certainly, back in the summer, we were looking to take advantage of that dynamic as we went to large scale.

麥克，也許值得我添加一點，只是為了澄清我們所有的詞彙，對嗎？我們使用「季節性」這樣的術語，是因為 HCP 社區認為傳染病，尤其是呼吸道傳染病，有「季節」特徵，當然，早在夏天，我們就希望利用這種動態，因為我們走向大規模。

COVID-19 disease, SARS-CoV-2 is not seasonal at all. It's ever present, pervasive and presents with periodic waves, right? The periodicity of the wave, it might be biannual or triannual or frankly, we may have yet to see what a true equilibrium looks like. I think a part of what Tim is getting at is that at the scale we are reaching right now, which, in our view, is very small, I don't know that we would see any particular effect of seasonality because we are so early in our growth.

COVID-19 疾病 SARS-CoV-2 根本不具有季節性。它始終存在、無所不在並以周期性的波動呈現，對嗎？波浪的周期可能是每兩年一次或每三年一次，或者坦白說，我們可能還沒有看到真正的平衡是什麼樣子。我認為蒂姆的部分意思是，就我們目前達到的規模而言，在我們看來，這個規模非常小，我不知道我們是否會看到季節性的任何特殊影響，因為我們還處於早期階段在在我們的成長中。

But I think it's also fair to say that as we scale a business, it would be natural and rational to have some relationship to at least periodicity. And while it may be confusing, we may from time to time and certainly HCPs and the vulnerable may refer to seasonality. But I think it's too early to worry or wonder about Q4 into Q1. I think the point that Tim is trying to convey is that from a growth standpoint, we feel so young and so early in our penetration into the highly vulnerable population, I don't think we believe we've yet achieved the scale where those kinds of dynamics will come to the fore, but we'll all have to find out together.

但我認為，也可以公平地說，隨著我們擴大業務規模，至少與週期性有某種關係是自然且合理的。雖然這可能令人困惑，但我們有時，尤其是醫療照護人員和弱勢群體可能會提到季節性。但我認為現在擔心或懷疑第四季對第一季的影響還為時過早。我認為蒂姆想要表達的觀點是，從成長的角度來看，我們感覺還很年輕，在高度脆弱人群中的滲透還處於早期階段，我認為我們還沒有達到那種規模。凸顯出來，但我們都必須共同尋找答案。

Thank you.

謝謝。

Jason Kolbert, D. Boral Capital.

Jason Kolbert，D.Boral Capital。

Good morning. Thank you very much. Yeah, I saw the R&D number came in very high, but it corresponds, I'm sure, almost one to one with the inventory build, which showed up on the balance sheet. My question is, what is the real -- what is the commercial value of that inventory on the balance sheet? It's obviously substantially higher than what you're carrying at.

早安.非常感謝。是的，我看到研發數字很高，但我確信，它與資產負債表上顯示的庫存累積幾乎是一一對應的。我的問題是，資產負債表上該庫存的真實商業價值是多少？這顯然比你攜帶的數量要高得多。

Yeah. I can -- Bill can comment a little bit. In general, I don't think we want to get into the level of specifics that would reveal sort of temporary net pricing by implication. But let's just say it this way. Invivyd has produced or is wrapping up production of well in excess of hundreds of millions of dollars of product inventory in revenue terms. And the accounting of that, I think, will flow through in the coming quarters as diminished spending.

是的。我可以——比爾可以發表一點評論。總的來說，我認為我們不想深入探討那些會暗示臨時淨定價的具體問題。但我們就這樣說吧。從收入來看，Invivyd 已經生產或正在完成超過數億美元的產品庫存的生產。我認為，這一現象將在未來幾季以支出減少的形式反映出來。

Bill, would you add anything to that?

比爾，你還有什麼補充嗎？

No, I think that's very well stated. Part of the reason for that discrepancy between what Marc has said for the market value and what we're carrying at is don't forget that we expensed a large amount of PEMGARDA costs prior to EUA -- granting of the EUA.

不，我認為這個表述得很好。馬克所說的市場價值和我們的實際價值之間存在差異，部分原因是別忘了我們在獲得 EUA 之前已經花費了大量 PEMGARDA 成本。

So costs that were incurred as we led up to the EUA to the point that those inventory amounts have not yet been sold through remain on our balance sheet. So that's a piece of why the discrepancy between our inventory balance on the balance sheet and what the market external value would be as those inventory amounts are sold through.

因此，在我們達成 EUA 之前產生的成本，以至於那些庫存金額尚未售出，仍然留在我們的資產負債表上。這就是為什麼我們的資產負債表上的庫存餘額與庫存售出後的市場外部價值有差異的原因之一。

Thank you very much. And I just want to ask you kind of a probing question. When you look at how to engineer a more potent or next-generation formula of PEMGARDA and even potentially moving from IV to IM or subcu, what do you scientifically have to do? How do you make those changes? Can you give us some insights into your process?

非常感謝。我只是想問你一個探索性的問題。當您研究如何設計更有效或更新一代的 PEMGARDA 配方，甚至可能從 IV 轉向 IM 或皮下注射時，您在科學上必須做什麼？您如何做出這些改變？能向我們介紹一下您的流程嗎？

Yeah. And look -- this is Marc. Your bad luck is that, oh, wait, actually, Robbie is logged in. So he will be able to rapidly clean up whatever I tell you that he feels is off base. But the reality is we've already done that work and it's well manifested in our next-generation molecule, VYD2311, right, which is in its first-in-human study right now.

是的。看——這是馬克。你的運氣不好，哦，等等，實際上， Robbie 已經登入了。這樣，他就能快速糾正我告訴你的他認為不合理的事。但事實上我們已經完成了這項工作，並且它在我們的下一代分子 VYD2311 中得到了很好的體現，目前正在進行首次人體研究。

What we effectively do is avail ourselves of a vast combinatorial library that can interrogate spike protein and offer up hits almost in the manner of if you're familiar with small molecule chemistry screening, right? And so we can select antibodies with enhanced biophysical properties by screening combinatorial libraries against spike protein that is, let's say, more and more contemporary.

我們實際上所做的就是利用一個龐大的組合庫，它可以查詢刺突蛋白並提供匹配結果，就像你熟悉小分子化學篩選一樣，對嗎？因此，我們可以透過篩選針對越來越現代的刺突蛋白的組合庫來選擇具有增強生物物理特性的抗體。

And in doing that, what we discover is that we are able to substantially enhance our potency with very modest changes to the overall structural identity of pemivibart and which is indeed itself not so, so different structurally than adintrevimab. So you might even think of it as a process of directed molecular honing in which we are continuing to interrogate what appears to be a pretty enriched site on the spike, which should not be surprising given the foundational hypothesis of the company, right, that there are these territories on spike that are essential for ACE2 access and therefore, essential for viral fitness and we wish to exploit that via monoclonal antibody.

在這樣做的過程中，我們發現，我們能夠透過對 pemivibart 的整體結構特性進行非常適度的改變來顯著提高其效力，而且 pemivibart 本身在結構上與 adintrevimab 並沒有太大的不同。所以你甚至可以把它看作是一個定向分子磨練的過程，在這個過程中，我們繼續詢問似乎在尖峰上相當豐富的位置，這並不奇怪，因為該公司的基本假設是，這些區域對於ACE2 的進入至關重要，因此對於病毒的適應性也至關重要，我們希望透過單株抗體來利用這一點。

Now that is easier said than done and involves a lot of technological tricks and sort of trade secret as it were in our approach. Other companies do not have access to those sorts of technology stacks and approaches. So we feel particularly proud of having done this work now on our third cut. But to the extent that I've glossed it over in simplistic terms, feel free to follow up with Robbie, or Robbie, by all means, correct anything I said.

現在，說起來容易做起來難，並且在我們的方法中涉及到很多技術技巧和商業機密。其他公司無法獲得此類技術堆疊和方法。因此，我們對在第三次剪輯中完成這項工作感到特別自豪。但是，如果我用過於簡單的術語掩蓋了這一點，請隨時與 Robbie 聯繫，或者 Robbie 盡一切努力糾正我所說的任何內容。

No, I think that the description that you provide embraces the answer to the question that was asked definitely in terms of how we go about doing this. The one thing I will add is that we are equipped in the laboratory to do this at any time and we do it all the time. And so we are constantly updating our working knowledge of how antibodies are acting against current variants and looking into future space using the technologies that we have to assure ourselves that antibodies will maintain activity to meet the target product profile that we've described and enabled through PEMGARDA and will enable through 2311 and on. So hopefully, that helps with your question.

不，我認為您提供的描述明確地回答了有關我們如何做到這一點的問題。我要補充的一點是，我們實驗室配備了隨時可以進行此項操作的設備，而且我們也一直都在這樣做。因此，我們不斷更新關於抗體如何對抗當前變異株的知識，並利用現有技術展望未來，以確保抗體能夠保持活性，以滿足我們描述和實現的目標產品特性。希望這對您的問題有幫助。

Yeah. You actually answered my follow-on question, which is it sounds like the platform is going to ultimately show utility beyond PEMGARDA and COVID.

是的。您實際上回答了我的後續問題，聽起來該平台最終將顯示超越 PEMGARDA 和 COVID 的效用。

Yeah. I think that particularly in situations where we have dynamic targets, that have conventionally required a great deal of a periodic vaccine effort or even a monoclonal antibody effort, we have an ability to address those types of dynamic targets that is borne out through the work we've done in COVID. So that's very true.

是的。我認為，特別是在我們有動態目標的情況下，這些目標通常需要大量的定期疫苗工作，甚至是單株抗體工作，我們有能力解決這些類型的動態目標，這一點已透過我們的工作得到證實在COVID 中所做的一切。這是千真萬確的。

Great update. Thanks so much, everybody.

很棒的更新。非常感謝大家。

(Operator Instructions) Patrick Trucchio, H.C. Wainwright.

(操作員指示) Patrick Trucchio，H.C.溫賴特。

Good morning team. This is [Louis] standing in for Patrick. I would like to ask a follow-up question also on VYD2311 regarding the regulatory authorization paths and lessons learned. So would there be a need for separate trials for treatment or prevention? Or based on the PEMGARDA fast-track, would there be a possibility that a new way could be approved for both treatment and prevention? I'm just thinking about an -- if there's an accelerated path forward for 2311. And then I have a follow-up question.

大家早安。這是代替派崔克的 [路易斯]。我還想就 VYD2311 提出一個有關監管授權路徑和經驗教訓的後續問題。那麼是否需要進行治療或預防的單獨試驗？或者基於PEMGARDA快速通道，是否有可能批准一種既能治療又能預防的新方法？我只是在想——2311 是否有一條加速前進的道路。然後我有一個後續問題。

Thanks. So the short answer is stay tuned and these are topics of active consideration, certainly at our end and we believe at FDA as well. It's important to remember that the treatment EUA application discussed and submitted in collaboration with the FDA indeed drew upon the same clinical data generated for our PrEP authorization, right?

謝謝。因此，簡短的回答是請繼續關注，這些都是我們正在積極考慮的話題，當然這是我們的考慮，我們相信 FDA 也是如此。重要的是要記住，與 FDA 合作討論和提交的治療 EUA 申請確實借鑒了我們為 PrEP 授權生成的相同臨床數據，對嗎？

At some level, an sVNA titer is an sVNA titer conferred by a given antibody. And Invivyd benefits from prior work with adintrevimab, which generated strong data from randomized controlled studies, demonstrating high clinical efficacy in the context of both treatment and PrEP. And indeed, those clinical benefit signals were conferred by the identical antibody at the identical dose in the identical route of administration. So we feel very confident scientifically that our work with pemivibart and certainly our work with 2311 represents the deployment clinically of very attractive antiviral titers.

在某種程度上，sVNA 滴度是由給定抗體賦予的 sVNA 滴度。Invivyd 受益於先前對 adintrevimab 的研究，該研究從隨機對照研究中獲得了強有力的數據，證明了在治療和 PrEP 方面均具有很高的臨床療效。事實上，這些臨床益處訊號是由相同劑量、相同給藥途徑的相同抗體賦予的。因此，我們在科學上非常有信心，我們在 pemivibart 方面的工作以及我們在 2311 方面的工作代表了非常有吸引力的抗病毒滴度在臨床上的部署。

And you sort of step back and ask yourself, how controversial a concept could this even be pharmaceutically, right? I don't think there are many people left on earth who wonder whether or not having some measure of antiviral activity, either when you are worried about encountering viral inoculum out in the community or when you are experiencing active infection, I think we universally regard that as a good thing.

然後你退一步問自己，從醫學角度來看，這個概念有多大的爭議呢，對吧？我認為，世界上沒有多少人會懷疑，無論是當你擔心在社區中遇到病毒接種物時，還是當你正在經歷活動性感染時，某種程度的抗病毒活性是否有效，我認為我們普遍認為這是一件好事。

And so I think we're in the business of passive prophylaxis with novel monoclonal antibodies generally and we would eagerly await to be in the business of treatment of active SARS-CoV-2 infection, particularly among immunocompromised persons in an outpatient context, we believe we can do those things.

因此，我認為我們通常使用新型單株抗體進行被動預防，並且我們熱切期待能夠進入治療活動性 SARS-CoV-2 感染的業務，特別是在門診環境中的免疫功能低下人群中，我們相信我們可以做到這些。

Now because we make novel antibodies, I think it is also safe to say that we and the FDA would jointly wish to assess the safety of these molecules in a reasonable and some of that data we have previously press released as a function of our discussions with FDA. And having done those things, we would look at the operative science and think to ourselves, well, my goodness, if we are bridging to predicate antibodies or if we are availing ourselves of more general concepts like a correlative protection, some of which you can read hot off the presses this morning in the New England Journal of Medicine, there are surrogates, which is, of course, the classical strategy for advancing rapid drug development and authorizations and/or approvals.

現在，由於我們生產新型抗體，我認為也可以肯定地說，我們和 FDA 共同希望以合理的方式評估這些分子的安全性，其中一些數據我們之前已根據與FDA。做完這些事情后，我們會看看操作科學，然後自言自語，天哪，我們是否正在橋接謂詞抗體，或者我們是否正在利用更一般的概念，如相關保護，其中一些你可以今天早上在《新英格蘭醫學雜誌》上讀到的最新消息是，有替代品，這當然是促進快速藥物開發和授權和/或批准的經典策略。

And so I think what pens on 2311 is we are currently gathering our in vivo first-in-human experience. We wish to assess safety and in vivo pharmacokinetics in operative human subjects through a variety of routes of administration. And then we will very much look forward to discussing those data with the FDA and in effect, dialoguing on how much residual uncertainty really remains in the category. I guess I'll pause there and ask Mark if you can add anything to that.

因此我認為 2311 號筆所指的是我們目前正在收集的首次人體體內實驗。我們希望透過多種給藥途徑評估手術人類受試者的安全性和體內藥物動力學。然後，我們將非常期待與 FDA 討論這些數據，並實際上討論該類別中究竟還剩下多少不確定性。我想我會在這裡停下來並問馬克你是否可以補充什麼。

No. I mean it was well said. I mean I think that we enjoy the -- as you mentioned, we enjoy the fact that the immunobridging concept that was employed for prevention is also directly able to be extrapolated to the treatment paradigm as well. So it really is, one, effectively, as you can imagine, exposure study, getting PK levels as well as titer levels and employing that versus the relevant variants at the time to make sure that our monoclonal antibody has protection across the current as well as with our embedded tools within Invivyd, our future -- the future variant landscape.

不。我的意思是說很好。我的意思是，我認為我們很享受——正如您所說，我們很享受這樣一個事實，即用於預防的免疫橋接概念也可以直接推廣到治療範式。因此，實際上，正如您所想像的那樣，暴露研究可以獲取 PK 水平以及滴度水平，並將其與當時的相關變體進行比較，以確保我們的單株抗體在當前和未來具有保護作用Invivyd 中嵌入的工具，我們可以實現我們的未來——未來的變體模式。

That makes a lot of sense. And regarding the follow-up question, it was, will this decision of a potential treatment and prevention rapid approval, will that depend on discussions on the titer threshold? In other words, if the path to approval in, say, prevention reaches a very high convincing compelling titer threshold, then maybe you can be more confident about an approval -- a rapid approval in treatment as well. And when can we have -- when do you expect to have that first readout for titers?

這很有道理。關於後續問題，這項關於潛在治療和預防的決定是否會迅速批准，是否取決於對滴度閾值的討論？換句話說，如果在預防方面的批准路徑達到了非常高的令人信服的滴度閾值，那麼也許你可以對批准更有信心——治療方面的快速批准。我們什麼時候可以獲得—您預計什麼時候可以獲得第一個滴度讀數？

Great. So again, Mark can add some detail. But I think we are in the process, of course, of doing the clinical work required to generate that profile in human subjects right now with 2311. As it goes to titer levels and confidence, I think our confidence is more or less unwavering for now about 2.5 years, right?

偉大的。因此，馬克可以再次添加一些細節。但我認為，我們目前正在利用 2311 在人類受試者身上進行生成該特徵所需的臨床工作。就滴度水平和信心而言，我認為我們的信心在大約 2.5 年內基本上是堅定不移的，對嗎？

So Invivyd employees previously published a lovely relationship in Science Translational Medicine showing antibody efficacy in a PrEP context down to very low titers. And you would have seen us very recently reminding ourselves and indeed the world and I think the FDA that that concept is generalizable, and I think we believe evergreen across all SARS-CoV-2 variants because we see that relationship repeat itself in our long-term CANOPY follow-up.

因此，Invivyd 員工之前在《科學轉化醫學》雜誌上發表了一篇可愛的關係文章，顯示了在 PrEP 環境中抗體的有效性，即使滴度非常低。你可能看到我們最近提醒我們自己，事實上，全世界，以及FDA，這個概念是可以推廣的，我認為我們相信所有SARS-CoV-2 變體都是常青樹，因為我們看到這種關係在我們的長期中重演。

So there's an aspect to the residual uncertainty here in which any reasonable person can say, well, if some antiviral titer is good, more is always better. The challenge, of course, is that that's not necessarily the pathway to an equitable scalable category of medicine, right? So if we have a hunger problem this Thanksgiving, I can solve it by getting you a good meal or I can try to solve it by asking you to sit and eat three turkeys. You will be full and potentially satisfied either way.

因此，這裡存在一個殘餘不確定性的方面，任何理性的人都可以說，如果某種抗病毒滴度是好的，那麼滴度越高越好。當然，挑戰在於，這不一定是通往公平可擴展的藥品類別的途徑，對嗎？因此，如果我們在這個感恩節遇到飢餓問題，我可以透過為你做一頓好飯來解決它，或者我可以嘗試透過讓你坐下來吃三隻火雞來解決它。無論哪種方式，您都會感到飽足和滿足。

The latter strategy, which is the strategy of seeking a very high dose and a very high titer, may leave a little bit to be desired in terms of the scalability and advisability of that strategy. So I think our view would be knowing that 2311 is, at least as we see it, a turn, maybe a good turn more potent than pemivibart would be to assess the pharmacokinetic profile, see how long of a half-life we have, calculate those titers and really reflect those titers against the totality of evidence that we've seen so far, right?

後一種策略，即尋求非常高劑量和非常高滴度的策略，在該策略的可擴展性和可取性方面可能有些不盡如人意。因此，我認為我們的觀點是，至少在我們看來，2311 是一個轉折點，也許比 pemivibart 更有效，可以評估藥物動力學特徵，看看我們的半衰期有多長，計算這些滴度確實反映了我們迄今為止所看到的全部證據，對嗎？

So the pemivibart immunobridging pathway to a data point drawn from the EVADE study, that is one data point. And I think a total of 12 clinical observations from the year 2021. We now have a wealth of data, including data from a contemporary context. And frankly, we're looking forward to someday seeing a publication of the AstraZeneca SUPERNOVA study because that may add a little more context in addition to our CANOPY data that says, hey, in a modern context, this relationship continues to hold.

因此，pemivibart 免疫橋接途徑是從 EVADE 研究中提取的數據點，即一個數據點。我認為 2021 年總共有 12 項臨床觀察。我們現在擁有大量的數據，包括來自當代背景的數據。坦白說，我們期待有一天能看到阿斯特捷利康 SUPERNOVA 研究的發表，因為這可能會在我們的 CANOPY 數據之外增加更多的背景信息，表明在現代背景下，這種關係仍然成立。

We can, we believe, because we're using such high-affinity, highly potent engineered recombinant antibodies, we can generate attractive clinical protection, we believe, at relatively low titers. Our goal as a company is not to serve at an extraordinary titer, a small number of people or a relatively smaller number of people. Our goal as a company is to democratize protection by conferring an appropriate amount of titer to the largest possible number of people because if you go back to the beginning, right, we -- our intention as Invivyd was never to create a niche or sort of, quote, orphan, unquote, drug for a virus that is so pervasive and damaging.

我們相信我們可以，因為我們使用的是這種高親和力、高效力的工程重組抗體，我們相信我們可以在相對較低的滴度下產生有吸引力的臨床保護。作為一家公司，我們的目標不是為超高滴度、少數人或相對較少的人提供服務。作為一家公司，我們的目標是透過為盡可能多的人提供適當數量的滴度來實現保護的民主化，因為如果你回到最初，我們作為 Invivyd 的意圖從來不是創造一個利基市場或某種，引用，孤兒，引號結束，針對這種如此普遍和具有破壞性的病毒的藥物。

So I guess each observer's mileage may vary when it comes to understanding and reflecting on the totality of clinical data generated to date. But I think from an Invivyd perspective, we feel very good about the potential benefit we can bring and are eager to scale protection to the maximum number of people. Does that make sense?

因此，我猜測，在理解和反映迄今為止產生的全部臨床數據時，每個觀察者的理解程度可能會有所不同。但我認為從 Invivyd 的角度來看，我們對可以帶來的潛在利益感到非常滿意，並渴望將保護範圍擴大到最大數量的人。這樣有道理嗎？

Thank you. That makes a lot of -- absolutely. Thank you.

謝謝。這確實有很多—絕對的。謝謝。

Thank you. And I would now like to hand the conference back over to Marc Elia for closing remarks.

謝謝。現在，我想將會議交還給馬克·埃利亞，請他作結語。

All right. Thanks, everybody, for joining us today. And indeed, it's an opportunity to reflect on what we hope has been a very unusual period in our corporate history. We are available all day for questions and answers. And again, we'll just get ourselves back to the business of trying to grow our core business and scale protection as fast as we can to as many people as we can. Thanks again. Bye bye.

好的。感謝大家今天的參與。事實上，我們希望這是一個反思公司歷史上非常不尋常時期的機會。我們全天都樂意解答您的問題。我們再說一遍，我們會重新回到主業，努力發展核心業務，並儘快擴大保護範圍，為盡可能多的人提供保護。再次感謝。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。