Invivyd Inc (IVVD) 2023 Q2 法說會逐字稿

Welcome to the Invivyd Second Quarter 2023 Business and Financial Results Update Call. I will now turn the call over to Gabriella Linville-Engler, Director of External Communications.

歡迎參加 Invivyd 2023 年第二季度業務和財務業績更新電話會議。我現在將把電話轉給外部傳播總監加布里埃拉·林維爾-恩格勒 (Gabriella Linville-Engler)。

Thank you for joining us today. Before we get started, I want to tend to a few housekeeping items. I invite you to review our press release discussing our second quarter 2023 financial results and business updates, which can be found on the Investors section of the Invivyd website.

感謝您今天加入我們。在我們開始之前，我想先處理一些家務用品。我邀請您查看我們討論 2023 年第二季度財務業績和業務更新的新聞稿，這些新聞稿可以在 Invivyd 網站的投資者部分找到。

I would like to remind you that during today's discussion, we will be making several forward-looking statements. Forward-looking statements include statements concerning, among other things, the future of the COVID-19 landscape, our ongoing research and clinical development plans, including the timing of these plans, our regulatory and commercialization plans, strategies and opportunities, our expected cash runway and other statements that are not historical facts.

我想提醒您，在今天的討論中，我們將做出一些前瞻性陳述。前瞻性陳述包括有關 COVID-19 形勢的未來、我們正在進行的研究和臨床開發計劃的陳述，包括這些計劃的時間安排、我們的監管和商業化計劃、戰略和機會、我們的預期現金跑道以及其他不屬於歷史事實的陳述。

Forward-looking statements are subject to a number of risks and uncertainties that may cause our actual results to differ materially from those expressed or implied in the forward-looking statements, including those described under the heading Risk Factors in our filings made with the U.S. Securities and Exchange Commission, including our most recent Form 10-K.

前瞻性陳述受到許多風險和不確定性的影響，這些風險和不確定性可能導致我們的實際結果與前瞻性陳述中明示或暗示的結果存在重大差異，包括我們向美國證券公司提交的文件中“風險因素”標題下描述的結果和交易委員會，包括我們最新的 10-K 表格。

It is now my pleasure to introduce the Invivyd management team to the call. I am joined by Dave Hering, CEO of Invivyd; and Dr. Pete Schmidt, Chief Medical Officer.

現在我很高興向大家介紹 Invivyd 管理團隊。 Invivyd 首席執行官 Dave Hering 也加入了我的行列；和首席醫療官 Pete Schmidt 博士。

I will now turn the call over to Dave.

我現在將把電話轉給戴夫。

Thanks, Gabriella, and thank you to everyone joining us today on our quarterly update call. In Q2, in the recent weeks, we've made significant progress towards our goal of commercializing VYD222 in the near term and advancing our mission to protect vulnerable people from serious viral threats.

謝謝加布里埃拉，也感謝今天參加我們季度更新電話會議的所有人。在第二季度，最近幾週，我們在實現近期 VYD222 商業化的目標以及推進我們保護弱勢群體免受嚴重病毒威脅的使命方面取得了重大進展。

Since our last call, we have announced positive initial safety data and robust serum neutralizing tighter data from our ongoing VYD222 Phase I clinical trial. We believe that the initial Phase I results are very encouraging and speak to the potential for VYD222 to provide vulnerable people, such as immunocompromised, with robust protection from symptomatic COVID-19. Shortly, Pete will provide additional color on the initial Phase I clinical trial results and our plans to rapidly initiate a 750-participant pivotal clinical trial of VYD222 for the prevention of symptomatic COVID-19 referred to as the CANOPY trial.

自上次電話會議以來，我們宣布了來自我們正在進行的 VYD222 I 期臨床試驗的積極的初始安全數據和更嚴格的血清中和數據。我們相信，第一階段的初步結果非常令人鼓舞，並說明了 VYD222 為弱勢群體（例如免疫功能低下者）提供針對有症狀的 COVID-19 的強大保護的潛力。很快，Pete 將提供有關初始I 期臨床試驗結果的更多信息，以及我們計劃快速啟動一項由750 名參與者參與的VYD222 關鍵臨床試驗，用於預防有症狀的COVID-19，稱為CANOPY試驗。

With the compact size of CANOPY and a primary efficacy endpoint based on the analysis of serum neutralizing titers at day 28, the same biomarker used in our Phase I clinical trial, we believe that we can swiftly enroll the trial and generate the clinical data necessary to enable a potential emergency use authorization, or EUA submission. We look forward to initiating the CANOPY trial in the near term and expect to have initial primary endpoint data by approximately the end of 2023.

憑藉 CANOPY 的緊湊尺寸和基於第 28 天血清中和滴度分析的主要療效終點（與我們的 I 期臨床試驗中使用的生物標誌物相同），我們相信我們可以迅速註冊試驗並生成必要的臨床數據啟用潛在的緊急使用授權或EUA 提交。我們期待在短期內啟動 CANOPY 試驗，並預計在 2023 年底左右獲得初始主要終點數據。

In Q2, we also announced that we reached general alignment with the FDA on a pathway to a potential EUA for VYD222 and anticipated follow-on candidates designed to prevent symptomatic COVID-19. We are very encouraged by the rapid development pathway outlined by the FDA and the opportunity it provides to leverage our previous work developing adintrevimab to accelerate the development of VYD222. We believe we are one of very few companies positioned to potentially meet the criteria that the FDA outlined for this streamlined development pathway.

在第二季度，我們還宣布與 FDA 就 VYD222 的潛在 EUA 途徑以及旨在預防症狀性 COVID-19 的預期後續候選藥物達成總體一致。 FDA 概述的快速開發途徑及其為利用我們之前開發 adintrevimab 的工作來加速 VYD222 的開發提供了機會，我們對此感到非常鼓舞。我們相信，我們是極少數有可能滿足 FDA 為這一簡化開發途徑制定的標準的公司之一。

Importantly, with this pathway, we see a near-term opportunity to bring much needed protection from symptomatic COVID-19 to immunocompromised people. Before I hand the call over to Pete to talk about our plans for the transformational period ahead, I want to briefly underscore 3 important points. First, the need to protect vulnerable populations from COVID-19 remains as urgent as ever. Immunocompromised people continue to be at higher risk for severe COVID-19 related outcomes. And more broadly, COVID-19 continues to be a deadly threat. Roughly halfway through 2023, before we have even entered the fall and winter months, the CDC estimates that more than 43,000 deaths in the U.S. are attributable to COVID-19 this year. That is more than 43,000 deaths where COVID-19 was listed as the underlying cause or a contributing cause of death on the death certificate.

重要的是，通過這條途徑，我們看到了近期的機會，可以為免疫功能低下的人提供急需的針對有症狀的 COVID-19 的保護。在我將電話交給皮特談論我們未來轉型期的計劃之前，我想簡要強調 3 個要點。首先，保護弱勢群體免受新冠肺炎 (COVID-19) 感染的需要仍然像以往一樣緊迫。免疫功能低下的人出現嚴重 COVID-19 相關後果的風險仍然較高。更廣泛地說，COVID-19 仍然是一個致命的威脅。大約到 2023 年已過半，在進入秋季和冬季之前，CDC 估計今年美國有超過 43,000 人死於 COVID-19。超過 43,000 例死亡病例在死亡證明上被列為根本原因或促成死亡原因的是 COVID-19。

For context, consider that RSV is estimated to cause roughly 14,000 deaths per year in the U.S. among the groups at highest risk for RSV and that pre-COVID levels for flu-related deaths have fluctuated between 23,000 and 52,000 deaths per year in the United States. COVID-19 remains a substantial driver of morbidity as well. The National Center for Health Statistics estimates that roughly 1 in 7 adults in the U.S. have experienced long COVID at some point, which adds to the unique and unacceptable burden of this disease.

作為背景，考慮到在美國，RSV 每年導致大約 14,000 人死亡，其中屬於 RSV 風險最高的群體，而在新冠疫情之前，美國流感相關死亡人數在每年 23,000 至 52,000 人之間波動。 COVID-19 仍然是發病率的一個重要驅動因素。美國國家衛生統計中心估計，美國大約有七分之一的成年人曾在某個時期經歷過長期新冠病毒感染，這增加了這種疾病獨特且不可接受的負擔。

While many have accepted the status quo and are trying to live with COVID, we continue to argue that all are not living well, particularly vulnerable population. Second, we believe that protecting immunocompromised people from COVID-19 is a large ongoing need and opportunity. In the U.S. alone, there are an estimated 8 million to 18 million immunocompromised people who may not generate robust protection from vaccines. To our knowledge, Invivyd is one of very few companies in the clinic now with a monoclonal antibody candidate in development for the prevention of COVID-19 in this population.

儘管許多人已經接受現狀並試圖與新冠病毒共存，但我們仍然認為，所有人都生活得不好，尤其是弱勢群體。其次，我們認為保護免疫功能低下的人免受 COVID-19 的侵害是一項巨大的持續需求和機遇。僅在美國，估計就有 800 萬至 1800 萬免疫功能低下的人可能無法通過疫苗獲得強有力的保護。據我們所知，Invivyd 是臨床上極少數正在開髮用於預防該人群中的 COVID-19 的單克隆抗體候選藥物的公司之一。

Consider that Evusheld alone captured $2.2 billion in total revenue in 2022 with strong growth prior to its removal from the market when it lost activity against emerging SARS-CoV-2 variance of concern. In a recent survey we conducted with nearly 200 U.S. physicians who treat different types of immunocompromised patients, 76% of respondents said they would be extremely likely or somewhat likely to use Evusheld for the immunocompromised patients if it were still available and relevant to circulating COVID-19 strain. In the coming periods, we look forward to sharing more insights from the market research we've conducted to further refine our understanding of the different immunocompromised population and the views of the clinicians who care for the different types of patients who may be chronically or temporarily immunocompromised.

考慮一下，僅 Evusheld 就在 2022 年獲得了 22 億美元的總收入，並實現了強勁增長，但由於失去了針對新出現的 SARS-CoV-2 變異的活性，該公司被退出市場。在我們最近對近200 名治療不同類型免疫功能低下患者的美國醫生進行的一項調查中，76% 的受訪者表示，如果Evusheld 仍然可用且與正在流行的新冠病毒相關，他們極有可能或在一定程度上可能將Evusheld 用於免疫功能低下患者。 19株。在接下來的時期，我們期待分享我們進行的市場研究的更多見解，以進一步完善我們對不同免疫功能低下人群的理解，以及護理不同類型的慢性或暫時性免疫功能低下患者的臨床醫生的觀點。免疫功能低下。

Third, we believe that Invivyd is uniquely positioned to rapidly and perpetually deliver mAb therapies that can keep pace with viral evolution and protect the vulnerable. Our company and our discovery platform are built on the premise that serial innovation will be required to provide vulnerable populations with continuous access to mAb therapies that protect against serious viral threats, a strategy that is similar to the approach used to periodically modify vaccines in response to viral evolution.

第三，我們相信 Invivyd 具有獨特的優勢，能夠快速、永久地提供能夠跟上病毒進化步伐並保護弱勢群體的單克隆抗體療法。我們公司和我們的發現平台建立在這樣的前提下：需要進行系列創新，以便為弱勢群體提供持續獲得單克隆抗體療法的機會，以抵禦嚴重的病毒威脅，這一策略類似於定期修改疫苗以應對病毒威脅的方法。病毒進化。

To anticipate and quickly respond to viral evolution, we are leveraging state-of-the-art viral surveillance, predictive modeling and advanced antibody engineering techniques designed to generate a pipeline of optimized mAb candidates that could be deployed in the future. We see COVID-19 as the optimal starting point for Invivyd due to the speed with which products can be brought to the market using the EUA pathway. From there, we believe that our platform could also be applied to protect vulnerable people from other viral threats such as influenza, an area where we have an early discovery stage program.

為了預測并快速應對病毒進化，我們正在利用最先進的病毒監測、預測模型和先進的抗體工程技術，旨在生成一系列可在未來部署的優化單克隆抗體候選藥物。我們認為 COVID-19 是 Invivyd 的最佳起點，因為使用 EUA 途徑將產品推向市場的速度很快。從那時起，我們相信我們的平台也可以用於保護弱勢群體免受其他病毒威脅，例如流感，這是我們有一個早期發現階段計劃的領域。

I will now pass the call to Pete Schmidt, our Chief Medical Officer, to discuss in more detail our initial Phase I data, pivotal clinical trial plans and regulatory pathway.

我現在將致電我們的首席醫療官 Pete Schmidt，更詳細地討論我們的初始 I 期數據、關鍵臨床試驗計劃和監管途徑。

Thank you, Dave. We are pleased to have recently shared positive initial data from our ongoing Phase I clinical trial of VYD222 which enrolled 30 healthy volunteers across 3 different dosing cohorts. Participants were randomized 8:2 to VYD222 or placebo. The initial Phase I clinical trial data showed that a single administration of VYD222 was generally well tolerated at all 3 dose levels tested with no serious adverse events reported. As expected, we saw a dose-dependent increase in serum neutralizing titers against Omicron XBB1.5. At the lowest dose tested, 1,500 milligrams, the geometric mean serum neutralizing titers were 3,245 against Omicron XBB1.5 at day 7, a geometric mean 39-fold rise from baseline.

謝謝你，戴夫。我們很高興最近分享了我們正在進行的 VYD222 I 期臨床試驗的積極初步數據，該試驗在 3 個不同的劑量組中招募了 30 名健康志願者。參與者以 8:2 的比例隨機分配至 VYD222 或安慰劑組。最初的 I 期臨床試驗數據顯示，VYD222 的單次給藥在所有 3 個測試劑量水平下總體耐受性良好，沒有報告嚴重不良事件。正如預期的那樣，我們看到針對 Omicron XBB1.5 的血清中和滴度呈劑量依賴性增加。在測試的最低劑量（1,500 毫克）下，第 7 天針對 Omicron XBB1.5 的幾何平均血清中和滴度為 3,245，幾何平均數較基線上升 39 倍。

At the 2,500 milligram dose, the titers were 9,647. At the 4,500 milligram dose, the titers were 16,865. As a point of reference, even the lowest VYD222 dose tested resulted in higher serum neutralizing titers against Omicron XBB1.5 than the titer shared at the recent Vaccines Advisory Committee meeting from investigational XBB-targeted vaccines that were administered to adults who are not on immunosuppressive treatment.

在 2,500 毫克劑量下，滴度為 9,647。在 4,500 毫克劑量下，滴度為 16,865。作為參考，即使測試的最低VYD222 劑量也會導致針對Omicron XBB1.5 的血清中和滴度高於最近疫苗諮詢委員會會議上分享的針對未接受免疫抑制的成年人注射的研究性XBB 靶向疫苗的滴度治療。

Higher VYD222 doses resulted, as expected, in higher titer levels that were well above those reported vaccine titer levels. Serum neutralizing titer data are meaningful because COVID-19 vaccine and mAb clinical trials, including our past Phase II/III adintrevimab clinical trial for the prevention of COVID-19 referred to as EVADE have demonstrated that serum-neutralizing titers are correlated with the prevention of COVID-19. This correlation has also been observed in immune-compromised individuals receiving Evusheld, a mAb that targets the spike protein receptor binding domain of SARS-CoV-2 like VYD222.

正如預期的那樣，更高的 VYD222 劑量會產生更高的滴度水平，遠高於報導的疫苗滴度水平。 Serum neutralizing titer data are meaningful because COVID-19 vaccine and mAb clinical trials, including our past Phase II/III adintrevimab clinical trial for the prevention of COVID-19 referred to as EVADE have demonstrated that serum-neutralizing titers are correlated with the prevention of COVID-19.在接受 Evusheld 治療的免疫受損個體中也觀察到了這種相關性，Evusheld 是一種針對 SARS-CoV-2 刺突蛋白受體結合域（如 VYD222）的單克隆抗體。

Based on this correlation, we believe that the serum neutralizing titers seen in our Phase I clinical trial are highly encouraging and support the potential for VYD222 to provide clinically meaningful protection from symptomatic COVID-19. With positive initial Phase I data in hand, we are pleased to have now solidified the design of our CANOPY trial of VYD222 for the prevention of symptomatic COVID-19, which is geared to support a potential EUA submission. We plan to enroll approximately 750 participants total across 2 cohorts in parallel.

基於這種相關性，我們相信在我們的 I 期臨床試驗中看到的血清中和滴度非常令人鼓舞，並支持 VYD222 為有症狀的 COVID-19 提供具有臨床意義的保護的潛力。有了積極的第一階段初步數據，我們很高興現在已經鞏固了 VYD222 CANOPY 試驗的設計，用於預防有症狀的 COVID-19，該試驗旨在支持潛在的 EUA 提交。我們計劃同時招募 2 個隊列中總共約 750 名參與者。

In Cohort A, we expect to enroll approximately 300 participants who are significantly immune compromised. This cohort may include, for example, people who are actively being treated for solid tumors, people with hematological malignancies, such as acute leukemia or multiple myeloma regardless of treatment status as well as other groups of people who have weakened immune systems as a result of a medical condition and/or immunosuppressive treatment. All participants in Cohort A will receive VYD222 administered via IV infusion and the co-primary endpoints will be safety and tolerability and serum neutralizing titers at day 28.

在 A 組中，我們預計將招募大約 300 名免疫功能嚴重受損的參與者。例如，該隊列可能包括正在積極接受實體瘤治療的人、患有血液系統惡性腫瘤（例如急性白血病或多發性骨髓瘤，無論治療狀況如何）的人，以及因以下原因而導致免疫系統減弱的其他人群：醫療狀況和/或免疫抑制治療。 A組中的所有參與者將接受通過靜脈輸注施用的VYD222，共同主要終點將是安全性和耐受性以及第28天時的血清中和滴度。

In this cohort, the primary efficacy analysis will use an immunobridging approach, comparing data obtained in CANOPY for VYD222 to certain historical data from our previous clinical trial of adintrevimab in which serum neutralizing titers correlated with observed clinical efficacy.

在該隊列中，主要療效分析將使用免疫橋接方法，將 CANOPY 中獲得的 VYD222 數據與我們之前的 adintrevimab 臨床試驗的某些歷史數據進行比較，其中血清中和滴度與觀察到的臨床療效相關。

In Cohort B, we plan to enroll approximately 450 participants who are at risk for exposure to SARS-CoV-2, which is essentially anyone who has regular unmasked interaction with others. Participants in Cohort B will be randomized 2:1 to receive VYD222 or placebo administered via IV infusion. In Cohort B, the primary endpoint will be safety and tolerability. Secondary and exploratory endpoints will include serum neutralizing titers and clinical efficacy.

在 B 組中，我們計劃招募大約 450 名有暴露於 SARS-CoV-2 風險的參與者，這基本上是任何經常與他人進行不戴口罩互動的人。 B 組的參與者將以 2:1 的比例隨機分配接受 VYD222 或通過靜脈輸注施用的安慰劑。在 B 組中，主要終點是安全性和耐受性。次要和探索性終點將包括血清中和滴度和臨床療效。

We plan to initiate the CANOPY trial with the 4,500 milligram dose of VYD222. While we believe that all 3 doses tested in the Phase I clinical trial have the potential to provide clinically meaningful protection against symptomatic COVID-19, we have decided to initiate the CANOPY trial with the dose that provided the highest serum neutralizing titers against Omicron XBB1.5. This decision was informed by the FDA's preference for a conservative serum-neutralizing titer benchmark and the 4,500 milligram dose. We believe this dose has the potential to provide a significant duration of protection while also providing protection against the potential loss of neutralization activity as SARS-CoV-2 evolves over time.

我們計劃用 4,500 毫克劑量的 VYD222 啟動 CANOPY 試驗。雖然我們相信I 期臨床試驗中測試的所有3 種劑量都有可能為有症狀的COVID-19 提供臨床上有意義的保護，但我們決定使用針對Omicron XBB1 提供最高血清中和滴度的劑量啟動CANOPY試驗。 5.這一決定是基於 FDA 對保守血清中和滴度基準和 4,500 毫克劑量的偏好。我們相信，該劑量有可能提供顯著持續時間的保護，同時還可以防止隨著 SARS-CoV-2 隨著時間的推移而演變，中和活性可能喪失。

For context, based on our own data from EVADE and other clinical studies of COVID-19 mAbs and vaccines, we believe there is strong clinical evidence that antibody-mediated protection against symptomatic COVID-19 may be achieved even at relatively low serum neutralizing titers on the order of 30 to 100. While we believe the 4,500 milligram dose of VYD222 is likely to provide titers well above the minimum level observed to provide clinically meaningful protection for a significant period of time, we are excited to continue rapidly advancing the VYD222 program while exploring in parallel possible opportunities to leverage other doses in the future.

就背景而言，根據我們自己來自EVADE 的數據以及其他COVID-19 單克隆抗體和疫苗的臨床研究，我們相信有強有力的臨床證據表明，即使在相對較低的血清中和滴度下，也可以實現針對症狀性COVID-19 的抗體介導的保護作用。 30 到100 的量級。雖然我們相信4,500 毫克劑量的VYD222 可能提供遠高於觀察到的最低水平的滴度，以在相當長的一段時間內提供有臨床意義的保護，但我們很高興繼續快速推進VYD222 計劃，同時同時探索未來利用其他劑量的可能機會。

As currently designed, all participants in the CANOPY trial will receive a second dose of VYD222 3 months after the initial dose. We plan to use the observed pharmacokinetic data from the trial in combination with the neutralization potency of VYD222 against relevant circulating SARS-CoV-2 variants to modify our redosing strategy as appropriate. With the size and design of CANOPY, we believe that we can quickly enroll the trial, given the strong interest we have seen from trial sites and immunocompromised people.

按照目前的設計，CANOPY 試驗的所有參與者將在初始劑量後 3 個月接受第二劑 VYD222。我們計劃將試驗中觀察到的藥代動力學數據與 VYD222 對相關循環 SARS-CoV-2 變異體的中和效力結合起來，酌情修改我們的重新給藥策略。鑑於我們從試驗地點和免疫功能低下的人群中看到了強烈的興趣，憑藉 CANOPY 的規模和設計，我們相信我們可以快速註冊試驗。

To facilitate enrollment in Cohort A, we have established a registry of recruitment-ready immunocompromised individuals for potential enrollment. We now have more than 1,000 potentially eligible individuals in our database, which we believe speaks to the strong unmet need. With clinical site selected, study drug available and many other activities already completed, we are pleased to be on track to initiate the CANOPY trial in the near term.

為了促進隊列 A 的註冊，我們建立了一個準備好招募的免疫功能低下個體的登記冊，以供潛在註冊。現在，我們的數據庫中有超過 1,000 名可能符合資格的個人，我們相信這說明了強烈的未滿足需求。隨著臨床地點的選擇、研究藥物的提供以及許多其他活動的完成，我們很高興能夠在短期內啟動 CANOPY 試驗。

Shifting to the regulatory pathway. As Dave briefly mentioned, the FDA has indicated that the use of a correlative protection or a surrogate of clinical efficacy in an immunobridging approach to a pivotal clinical trial may be a reasonable approach to support an EUA request for new mAb candidates when certain criteria are met. Specifically, when clinical efficacy data from a prototype mAb is available, provided that, one, the new mAb candidate is similar to the prototype mAb such that it leverages a consistent manufacturing platform and has limited structural and functional differences.

轉向監管途徑。正如 Dave 簡要提到的，FDA 已表示，在關鍵臨床試驗的免疫橋接方法中使用相關保護或臨床療效替代可能是在滿足某些標準時支持新 mAb 候選藥物 EUA 請求的合理方法。具體來說，當原型單克隆抗體的臨床療效數據可用時，前提是，第一，新的單克隆抗體候選者與原型單克隆抗體相似，因此它利用一致的製造平台，並且結構和功能差異有限。

And two, the new mAb has supportive nonclinical data, such as favorable in vitro neutralization data against currently circulating SARS-CoV-2 variants. We plan to leverage this immunobridging pathway in the U.S. to accelerate the clinical development of VYD222 and anticipated follow-on mAb candidates with our previous mAb candidate at adintrevimab or future proprietary mAb serving as the prototype mAb. We believe we are one of very few companies that can potentially meet all the criteria and utilize this accelerated development pathway for the prevention of COVID-19.

第二，新的單克隆抗體具有支持性的非臨床數據，例如針對當前流行的 SARS-CoV-2 變種的有利體外中和數據。我們計劃利用美國的這一免疫橋接途徑來加速 VYD222 和預期後續 mAb 候選藥物的臨床開發，其中我們之前的 mAb 候選藥物 adintrevimab 或未來的專有 mAb 作為原型 mAb。我們相信，我們是極少數有可能滿足所有標準並利用這種加速開發途徑來預防 COVID-19 的公司之一。

The use of adintrevimab as the potential prototype mAb is proprietary to Invivyd and enabled by the data from our previous Phase II/III clinical trial of adintrevimab for the prevention of symptomatic COVID-19, which had clinical event end points. In addition to utilizing previously generated adintrevimab data, we plan to use day 28 serum neutralizing titers from the immunocompromised cohort of CANOPY, along with safety data from both CANOPY cohorts to enable the clinical data package for a potential EUA submission for VYD222.

使用 adintrevimab 作為潛在的單克隆抗體原型是 Invivyd 專有的，並由我們之前用於預防症狀性 COVID-19 的 adintrevimab II/III 期臨床試驗的數據啟用，該試驗具有臨床事件終點。除了利用之前生成的 adintrevimab 數據外，我們還計劃使用來自 CANOPY 免疫功能低下隊列的第 28 天血清中和滴度以及來自兩個 CANOPY 隊列的安全性數據，為 VYD222 潛在 EUA 提交提供臨床數據包。

Looking outside the U.S., we continue to engage with global regulatory authorities regarding the VYD222 clinical development program. In closing, I'm very pleased with all the progress our team has made, and I'm optimistic about the opportunity we have to make a meaningful difference in the lives of some of the most vulnerable people in our communities. Viruses that typically cause minor illness in immunocompetent people can have devastating consequences for the immune compromised, which leads many of these individuals to self isolate from their loved ones and miss out on many important moments and activities. For the immune compromise, mAbs have the potential to provide the robust protection from viral threats that they require and deserve.

放眼美國以外，我們繼續就 VYD222 臨床開發計劃與全球監管機構進行接觸。最後，我對我們團隊取得的所有進展感到非常滿意，並且我對我們有機會為我們社區中一些最弱勢群體的生活做出有意義的改變感到樂觀。通常在免疫功能正常的人中引起輕微疾病的病毒可能會對免疫受損的人造成毀滅性的後果，這導致其中許多人與親人自我隔離，並錯過許多重要的時刻和活動。對於免疫損害，單克隆抗體有潛力提供其所需且應得的針對病毒威脅的強大保護。

With that, I will turn the call over to Dave to provide an overview of our financials before we open up the call for Q&A.

這樣，在我們開始問答之前，我會將電話轉給戴夫，以概述我們的財務狀況。

Thank you, Pete. The details of our second quarter financials are included in the press release issued earlier today, so I won't reiterate all of the details here. Invivyd ended the second quarter of 2023 with $298.4 million in cash, cash equivalents and marketable securities. Based on our current operating plans, we expect that our cash, excluding any potential revenue associated with VYD222, will enable us to fund our operating expenses into the fourth quarter of 2024.

謝謝你，皮特。我們第二季度財務數據的詳細信息已包含在今天早些時候發布的新聞稿中，因此我不會在此重申所有詳細信息。截至 2023 年第二季度，Invivyd 擁有 2.984 億美元現金、現金等價物和有價證券。根據我們當前的運營計劃，我們預計我們的現金（不包括與 VYD222 相關的任何潛在收入）將使我們能夠為 2024 年第四季度的運營費用提供資金。

As you may recall, in past quarters, we guided to the second half of 2024 on runway but have refined our guidance now that we have finalized the size of our CANOPY trial. We believe that we are well capitalized to execute on our strategy and create value for our stakeholders.

您可能還記得，在過去的幾個季度中，我們對跑道的指導時間為 2024 年下半年，但現在我們已經確定了 CANOPY 試驗的規模，因此對我們的指導進行了細化。我們相信，我們有充足的資本來執行我們的戰略並為利益相關者創造價值。

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

那麼，接線員，請打開提問電話。

(Operator Instructions) Our first question comes from Maxwell Skor with Morgan Stanley.

（操作員說明）我們的第一個問題來自摩根士丹利的 Maxwell Skor。

Congrats on the updates. Just can you elaborate a bit more on the profile of Cohort B? Will these patients be vaccinated, unvaccinated, boosted? And how do you plan to evaluate clinical efficacy? Also, did the FDA provide guidance related to how long you have to follow these patients to fulfill the safety requirements?

恭喜更新。您能詳細介紹一下 B 組的概況嗎？這些患者會接種疫苗、未接種疫苗還是加強免疫？您打算如何評估臨床療效？此外，FDA 是否提供了有關您必須跟踪這些患者多長時間才能滿足安全要求的指導？

Max, good question. In terms of Cohort B, this is what we call an allcomers cohort so we really aren't concerned with their vaccination or exposure status. And the clinical end points for that cohort will be as they were in EVADE, so symptomatic disease, anyone who gets symptomatic COVID. In terms of follow-up, we haven't really stated. We'll put those details up on clinicaltrials.gov when we initiate the trial.

麥克斯，好問題。就隊列 B 而言，這就是我們所說的所有人隊列，因此我們實際上並不關心他們的疫苗接種或暴露狀態。該隊列的臨床終點將與 EVADE 中的情況一樣，即有症狀的疾病，即任何有症狀的新冠病毒患者。至於後續，我們還沒有真正表態。當我們啟動試驗時，我們會將這些詳細信息發佈在 ClinicalTrials.gov 上。

Our next question comes from Evan Wang with Guggenheim.

我們的下一個問題來自古根海姆的 Evan Wang。

Great to see all the progress from the Phase III. Had some follow-ups on the trial design. It does seem significantly smaller compared to the SUPERNOVA trial. So -- and I know there's a focus on garnering FC data from FDA. So is this smaller trial really just driven by the platform? And if you could share more color on generating some of the FC data?

很高興看到第三階段的所有進展。對試驗設計進行了一些跟進。與 SUPERNOVA 試驗相比，它看起來確實小得多。因此，我知道重點關注從 FDA 獲取 FC 數據。那麼這個較小的試驗真的只是由平台驅動的嗎？您是否可以分享更多有關生成一些 FC 數據的信息？

Second, on enrollment and down by year-end. Can you talk about what's remaining to get the trial started, confidence enrollment and whether you need both cohorts to file for approval especially it seems like it positions you pretty well versus AstraZeneca with your data by year-end?

其次，招生人數和年底前下降。您能否談談啟動試驗還需要做什麼、信心入組以及您是否需要兩個隊列都申請批准，尤其是到年底您的數據似乎與阿斯利康相比，您的地位相當好？

And then third, just thoughts in terms of the commercial opportunity of this immunocompromised and allcomers. I know the focus there has been on immunocompromised you're seeing. So just wondered if you have updated thoughts on some of the allcomers commercial opportunity.

第三，僅考慮免疫功能低下者和所有參與者的商業機會。我知道大家關注的焦點是你所看到的免疫功能低下。所以想知道您是否對一些所有來者的商業機會有更新的想法。

So I'll take the first part of this, and then, Pete, you can tag on. So as it relates to the size of the study versus SUPERNOVA. I mean, I can't comment specifically on why their trial is the size that it is, not knowing that. But I think what's key is we have started and had these conversations since that December FDA meeting where they had a joint FDA/EMA session talking specifically about how to accelerate mAb development in -- against COVID-19. And that's where they first started bringing up this prototype concept.

所以我將討論第一部分，然後，皮特，你可以繼續。因此，這與研究與超新星研究的規模有關。我的意思是，我無法具體評論為什麼他們的試驗規模如此之大，因為我並不知道這一點。但我認為關鍵是自去年 12 月 FDA 會議以來我們就開始並進行了這些對話，當時他們召開了 FDA/EMA 聯合會議，專門討論瞭如何加速針對 COVID-19 的單克隆抗體開發。這就是他們首先開始提出這個原型概念的地方。

And then certainly, as we are into our Phase I study, we got further detail, which we put forward in a press release talking about this immunobridging concept and being able to utilize specific data from adintrevimab. I think SUPERNOVA has gone through a variety of iterations and clinical trial design, which may have impacted that. I don't really know. But specifically, when we look at this, Cohort A allows you to get this titer level data quickly in a small subset of the overall trial. And then Cohort B gets you the necessary safety end that you need to put together a package for a potential EUA. You can talk a little bit, Pete, about starting and enrollment, some of the other pieces that Evan asked about.

當然，當我們進入第一階段研究時，我們獲得了進一步的細節，我們在新聞稿中提出了這些細節，討論了這種免疫橋接概念並能夠利用來自 adintrevimab 的具體數據。我認為 SUPERNOVA 經歷了各種迭代和臨床試驗設計，這可能會影響這一點。我真的不知道。但具體來說，當我們看到這一點時，隊列 A 允許您在整個試驗的一小部分中快速獲取該滴度水平數據。然後，群組 B 為您提供必要的安全目標，您需要為潛在的 EUA 整合一攬子計劃。皮特，你可以談談關於開始和註冊以及埃文詢問的其他一些問題。

Yes. And to clarify in Cohort B, it's exactly what Dave said. I don't think there's necessarily an intent to pursue a commercial opportunity there. That's really just to provide the supportive safety database as it's -- as you can imagine, it's easier to enroll allcomers than specifically the immune compromised.

是的。在 B 組中需要澄清的是，這正是 Dave 所說的。我認為不一定有尋求那裡商業機會的意圖。這實際上只是提供支持性安全數據庫，正如您可以想像的那樣，註冊所有參與者比專門註冊免疫受損的人更容易。

And in terms of recruitment and what we expect. I think it goes to what I was saying about this registry we created. So every individual in that registry has identified as immune compromise and has expressed interest in an interventional trial. So we are very pleased to have that ready database of over 1,000 individuals, and we think that a large proportion of them will be very interested enrolling quickly.

在招聘和我們的期望方面。我認為這符合我所說的我們創建的這個註冊表。因此，該登記處的每個人都被確定為免疫受損，並表達了對乾預試驗的興趣。因此，我們很高興擁有超過 1,000 人的現成數據庫，我們認為其中很大一部分人將非常有興趣快速註冊。

Yes. The only thing I'd add, Evan, as it relates to the commercial opportunity. I mean, we are focused on the vulnerable population, which could be argued to be just about all of us given the current state of protection and where we are with variants. With that said, our initial focus has always been on this immunocompromised group, folks who have been contraindicated against vaccines, et cetera, those who are at highest risk for severe outcomes from COVID-19.

是的。埃文，我唯一要補充的是，因為它與商業機會有關。我的意思是，我們關注的是弱勢群體，鑑於目前的保護狀態以及我們所處的變種情況，可以說這幾乎是我們所有人。話雖如此，我們最初的重點始終是這個免疫功能低下的群體，即那些對疫苗有禁忌的人等等，即那些因 COVID-19 出現嚴重後果的風險最高的人。

And in terms of activities necessary to initiate CANOPY, it's largely just the box checking stuff that you have to do before you start a trial. I think we've passed all the major hurdles. We haven't provided specific guidance on when we're going to start, but you can see that we did say we'll release some preliminary primary efficacy endpoint data by the end of -- by around the end of 2023.

就啟動 CANOPY 所需的活動而言，這很大程度上只是您在開始試用之前必須做的勾選工作。我認為我們已經克服了所有主要障礙。我們尚未提供有關何時開始的具體指導，但您可以看到，我們確實說過我們將在 2023 年底左右發布一些初步的主要療效終點數據。

Our next question comes from Michael Yee with Jefferies.

我們的下一個問題來自 Jefferies 的 Michael Yee。

This is [Jenna] on for Mike. We have 2 questions, if we may. First question is at this upcoming year-end readout of initial pivotal data, what are you looking to show? And what is the bar? Are you looking to replicate the Phase I results, which was already great? Or are you looking to show even higher titer levels?

這是邁克的[珍娜]。如果可以的話，我們有兩個問題。第一個問題是，在即將到來的年底公佈的初始關鍵數據中，您希望展示什麼？酒吧是什麼？您是否希望復制已經很棒的第一階段結果？或者您希望顯示更高的滴度水平？

And then second question is, from that point forward, what are the key milestones afterwards? And how soon could you expect to be on the market?

第二個問題是，從那時起，之後的關鍵里程碑是什麼？您預計多久會上市？

Yes. So, yes, so from the preliminary data that we're talking about around year-end, it would be similar to what we saw in the Phase I. It's the titer values. That said, it will be based on an analysis for day 28. So it's slightly different than the day 7 Phase I data that we provided there, but similar in terms of we're looking for high titer values. They don't have to be equivalent to the Phase I, but based on everything we saw from Phase I, it's repeating that in this Cohort A and getting some of that preliminary data. And so that would confirm what we've seen in Phase I and what we're expecting to see in CANOPY.

是的。所以，是的，從我們在年底討論的初步數據來看，它與我們在第一階段看到的類似。這是滴度值。也就是說，它將基於第 28 天的分析。因此，它與我們在那裡提供的第 7 天第一階段數據略有不同，但在我們尋找高滴度值方面相似。它們不必與第一階段相同，但根據我們從第一階段看到的一切，它在 A 組中重複這一點並獲取一些初步數據。因此，這將證實我們在第一階段所看到的以及我們期望在 CANOPY 中看到的。

Key milestones after, right, for an EUA submission, you need the clinical data. You need a preclinical set of activity, CMC, et cetera. We believe we can assemble all of that quite rapidly. And certainly, we'll provide more information and guidance as we get closer to this clinical information, et cetera. But certainly, it's something that we're looking to do as quickly as possible especially as we're starting to see an uptick in COVID cases, increase in hospitalizations, et cetera, even prior to the fall and winter season.

對於 EUA 提交，您需要臨床數據之後的關鍵里程碑。您需要一組臨床前活動、CMC 等。我們相信我們可以很快地組裝所有這些。當然，隨著我們接近這些臨床信息等，我們將提供更多信息和指導。但當然，我們希望盡快採取行動，尤其是在我們開始看到新冠病例上升、住院人數增加等情況下，甚至在秋冬季節之前也是如此。

And so certainly, it's not lost on us that time is of the essence and in a situation where there are no mAbs on the market, one that we're looking to rectify as quickly as we can.

因此，當然，我們並沒有忘記時間至關重要，而且在市場上沒有單克隆抗體的情況下，我們希望盡快糾正這種情況。

The next question comes from Patrick Trucchio with H.C. Wainwright.

下一個問題來自 Patrick Trucchio 和 H.C.溫賴特。

Congrats on the progress. I have a couple of follow-up questions. The first is just I'm wondering if you can talk about the new COVID variant, EG5. What have we seen so far with these cases of COVID-19? How different or similar is this variant to XBB1.5? And would you expect VYD222 to retain activity against this variant?

祝賀取得的進展。我有幾個後續問題。首先，我想知道您是否可以談談新的 COVID 變種 EG5。到目前為止，我們在這些 COVID-19 病例中看到了什麼？此變體與 XBB1.5 有什麼不同或相似之處？您是否期望 VYD222 保留針對該變體的活性？

Yes. On the first piece, right, I mean, we continue to see viral evolution. That's, I guess, one of the most critical components of the Invivyd strategy, right, which is we expect the virus to continue to evolve, which is why we see serial innovation as the answer, continuing to update antibodies, et cetera.

是的。在第一部分中，我的意思是，我們繼續看到病毒式進化。我想，這就是 Invivyd 策略最關鍵的組成部分之一，對吧，我們期望病毒繼續進化，這就是為什麼我們將系列創新視為答案，繼續更新抗體等等。

As it relates to EG5, we're looking to pull in and get in vitro data on it. But based on what we've seen so far, our belief is that it wouldn't cause a significant activity reduction to VYD222. And so we'll take a look at that now that it's the predominant variant and do some additional confirmatory test, et cetera.

由於它與 EG5 相關，我們正在尋求獲取有關它的體外數據。但根據我們迄今為止所看到的情況，我們認為這不會導致 VYD222 的活性顯著減少。因此，我們現在將研究它，因為它是主要變體，並進行一些額外的驗證性測試，等等。

I do think we've seen a progression from the summer into now, which is, like I said, not unexpected. We continue to do a variety of surveillance and predictive modeling on our side and look at mutation specifically, so even before they become specifically designated variants. And so that's how we continue to look at what do we see coming, which ones would we like to start to test against, how we start to bring in assays against those and prepare for different eventualities.

我確實認為我們已經看到了從夏天到現在的進展，正如我所說，這並不意外。我們繼續進行各種監測和預測建模，並專門研究突變，甚至在它們成為專門指定的變體之前。因此，這就是我們如何繼續關注我們所看到的未來，我們想要開始測試哪些內容，我們如何開始針對這些內容進行分析並為不同的可能性做好準備。

So that's really, like I said, embedded into how Invivyd is structured in our strategy and looking to assess and then respond to the different variants as they emerge.

所以，就像我說的那樣，這確實嵌入到了 Invivyd 戰略的構建方式中，並尋求評估並應對出現的不同變體。

And then just a clarification question. Is the expectation to have primary endpoint data from both Cohorts A and B at the end of 2023? And can you talk to us about the potential for government contracts for VYD222? Or would this be primarily be commercialized through sort of traditional channels and methods? And then just lastly, can you talk about advantages of VYD222 compared to some of these other antibodies in development for COVID-19? And what are some of the advantages perhaps of the dosing schedule or others that you can point to relative to those approaches?

然後只是一個澄清問題。是否期望在 2023 年底獲得隊列 A 和 B 的主要終點數據？您能和我們談談 VYD222 獲得政府合同的潛力嗎？還是主要通過某種傳統渠道和方法進行商業化？最後，您能談談 VYD222 與正在開發的其他一些針對 COVID-19 的抗體相比的優勢嗎？您可以指出相對於這些方法的給藥方案或其他方案有哪些優點？

I can take government contracts. You want to take first the preliminary data we're expecting from the primary endpoint at around the end of the year?

我可以接受政府合同。您想首先獲取我們預計在年底左右從主要終點獲得的初步數據嗎？

Yes, that's a good question. So our understanding and plan is actually that we don't need the serum neutralizing titer data from Cohort B there. That group just serves to increase the safety database, the exposure needed for an EUA. So the preliminary data you'll see will just be from the immune compromised cohort, which is Cohort A.

是的，這是一個好問題。所以我們的理解和計劃實際上是我們不需要來自 B 組的血清中和滴度數據。該小組的作用只是增加安全數據庫，即 EUA 所需的暴露程度。因此，您將看到的初步數據僅來自免疫受損隊列，即隊列 A。

Yes. And then related to your question about government contracts. Based on the current environment and transition, we are not anticipating government contracts as the primary source or really putting much in terms of our commercial readiness related to government contracts. We're preparing for a traditional market, your activities related to reimbursement in payers and market access, et cetera. And so that's really the focus of the team now as we're preparing for a potential launch and being ready for that in a traditional market.

是的。然後涉及到你關於政府合同的問題。基於當前的環境和轉型，我們並不期望政府合同成為主要來源，也沒有真正在與政府合同相關的商業準備方面投入太多精力。我們正在為傳統市場做準備，您的活動涉及付款人報銷和市場准入等。因此，這確實是團隊現在的重點，因為我們正在準備潛在的發布並為傳統市場做好準備。

That said, a variety of the different acts that Congress took during the pandemic do provide different reimbursements and things of coverage for Medicare, et cetera. And so we continue to look at all of those. So even without government contracts, as we saw during the pandemic, there still is a variety of support that has been put in place for COVID-related products.

也就是說，國會在大流行期間採取的各種不同法案確實為醫療保險等提供了不同的報銷和承保範圍。因此，我們將繼續關注所有這些。因此，即使沒有政府合同，正如我們在大流行期間看到的那樣，仍然為與新冠病毒相關的產品提供了各種支持。

As it relates to advantages of VYD222. One of the things that we've been saying for quite a while is 222 is a reengineered version of our original antibody ADG20. And we did this through an affinity maturation process and did it looking at the BA1, BA2 backbone of Omicron. And so with a set of slight changes, a, amino acids, we were able to reestablish binding where ADG20 has lost. ADG20 came from a SARS-CoV-1 survivor. And so we continue to see that 222 has broad neutralizing activity and is one that we really see as an antibody that, to date, has not occurred in a natural setting.

因為這涉及到VYD222的優點。我們已經說了很長一段時間的事情之一是 222 是我們原始抗體 ADG20 的重新設計版本。我們通過親和力成熟過程做到了這一點，並觀察了 Omicron 的 BA1、BA2 主幹。因此，通過一系列輕微的變化，a，氨基酸，我們能夠在 ADG20 丟失的地方重新建立結合。 ADG20 來自 SARS-CoV-1 倖存者。因此，我們繼續發現 222 具有廣泛的中和活性，並且我們確實將其視為迄今為止在自然環境中尚未出現的抗體。

And so we feel that it provides us a higher probability of duration of activity. And so that's what we continue to look at and test, but we think that's probably the most critical advantage, which is being able to have prolonged activity as our hypothesis for 222. Beyond that, we continue to see that by utilizing the adintrevimab, the ADG20 data, that allows this platform as well to be quite a significant advantage. As we said, we see that Invivyd is one of a few companies who could utilize existing data that was done previously. And that's quite an advantage as it relates to pursuing EUAs in a much faster fashion than running full clinical endpoint studies, especially given the current environment and looking to recruit patients.

因此我們認為它為我們提供了更高的活動持續時間概率。這就是我們繼續觀察和測試的內容，但我們認為這可能是最關鍵的優勢，即能夠延長活性，作為我們對 222 的假設。除此之外，我們繼續看到，通過使用 adintrevimab， ADG20 數據表明，該平台也具有相當顯著的優勢。正如我們所說，我們看到 Invivyd 是少數可以利用之前完成的現有數據的公司之一。這是一個相當大的優勢，因為它比運行完整的臨床終點研究更快地尋求 EUA，特別是考慮到當前的環境和尋求招募患者。

And I'm not showing any further questions at this time. I'd like to turn the call back over to Dave for any closing remarks.

目前我不會提出任何進一步的問題。我想將電話轉回給戴夫，讓他發表結束語。

Thank you all for joining the call today. It's a very exciting time for Invivyd as we get closer to milestones that we believe would be quite impactful for patients, our organization and shareholders. We thank you for your continued support and interest in Invivyd, and we will look forward to catching up with any of you individually over the coming days. Thank you so much.

感謝大家今天加入電話會議。對於 Invivyd 來說，這是一個非常激動人心的時刻，因為我們越來越接近里程碑，我們相信這些里程碑將對患者、我們的組織和股東產生相當大的影響。我們感謝您對 Invivyd 的持續支持和興趣，我們期待在未來幾天與你們單獨交流。太感謝了。

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect, and have a wonderful day.

女士們、先生們，今天的演講到此結束。您現在可以斷開連接，並度過美好的一天。