Inovio Pharmaceuticals Inc (INO) 2024 Q4 法說會逐字稿

Good afternoon ladies and gentlemen, and welcome to the Inovio Pharmaceuticals fourth quarter 2024 financial results conference call. (Operator Instructions) This call is being recorded on Tuesday, March 18, 2025. And I would now like to turn the conference over to Ms. Jennie Wilson, thank you, please go ahead.

女士、先生們下午好，歡迎參加 Inovio Pharmaceuticals 2024 年第四季財務業績電話會議。（操作員指示）此通話於 2025 年 3 月 18 日星期二錄製。現在我想將會議交給珍妮·威爾遜女士，謝謝，請繼續。

Good afternoon and thank you for joining the Inovio fourth quarter 2024 financial results conference call. Joining me on today's call will be Jackie -- Doctor Jackie Shea, President and Chief Executive Officer; Dr. Mike Sumner, Chief Medical Officer; Peter Kies, Chief Financial Officer; and Steve Egge, Chief Commercial Officer.

下午好，感謝您參加 Inovio 2024 年第四季財務業績電話會議。與我一起參加今天電話會議的還有 Jackie——總裁兼首席執行官 Jackie Shea 博士；首席醫療官 Mike Sumner 博士； Peter Kies，首席財務官；以及首席商務官 Steve Egge。

Today's call we'll review our corporate and financial information for the quarter and year ended December 31, 2024, as well as provide a general business update. Following prepared remarks, we will conduct a question-and-answer segment.

在今天的電話會議上，我們將回顧截至 2024 年 12 月 31 日的季度和年度的公司和財務信息，並提供一般業務更新。在準備好的發言之後，我們將進行問答環節。

During the call, we will be making forward-looking statements regarding future events and the future performance of the company. These events relate to our business plans to develop Inovio's DNA medicines platform, which includes clinical and regulatory developments and timing of clinical data readouts and planned regulatory submissions, along with capital resources and strategic matters.

在電話會議中，我們將就未來事件和公司未來表現做出前瞻性陳述。這些事件與我們開發 Inovio 的 DNA 藥物平台的業務計劃有關，其中包括臨床和監管發展、臨床數據讀數的時間和計劃的監管提交，以及資本資源和戰略事項。

All of these statements are based on the beliefs and expectations of management as of today; actual events or results could differ materially. We refer you to the documents we file from time to time with the SEC, which, under the heading risk factors, identify important factors that could cause actual results to differ materially from those expressed by the company verbally as well as statements made within this afternoon's press release.

所有這些聲明均基於管理層今天的信念和期望；實際事件或結果可能會有重大差異。請您參閱我們不時向美國證券交易委員會提交的文件，這些文件在「風險因素」標題下列出了可能導致實際結果與公司口頭表達的結果以及今天下午的新聞稿中的聲明存在重大差異的重要因素。

This call is being webcast live and a link can be found on our website, ir.inovio.com, and a replay will be made available shortly after this call is concluded. I will now turn the call over to Inovio's President and CEO, Dr. Jackie Shea.

本次電話會議將進行網路直播，連結可在我們的網站 ir.inovio.com 上找到，電話會議結束後不久將提供重播。現在我將電話轉給 Inovio 總裁兼執行長 Jackie Shea 博士。

Good afternoon and thank you to everyone for joining today's call. After significant progress in 2024, we remain focused on transforming Inovio into a commercial-stage company and delivering on the promise of DNA medicine for patients and shareholders alike.

下午好，感謝大家參加今天的電話會議。在 2024 年取得重大進展之後，我們仍致力於將 Inovio 轉變為商業階段的公司，並為患者和股東兌現 DNA 醫學的承諾。

To achieve that goal, our work this year will be driven by three main strategic priorities: submitting our BLA for INO-3107, our lead candidate for recurrent respiratory papillomatosis; advancing our commercial plans and preparing for a fast and efficient launch ; and leveraging the strengths of our platform to drive progress across our our diversified pipeline.

為了實現這一目標，我們今年的工作將圍繞三個主要戰略重點：提交 INO-3107 的 BLA，這是我們治療復發性呼吸道乳頭狀瘤的主要候選藥物；推進我們的商業計劃並為快速高效的發布做好準備；並利用我們平台的優勢推動我們多元化管道的進步。

Advancing 3107 is our primary focus, and I am very pleased to report that we have resolved the previously announced manufacturing issue involving the single-use array component of the CELLECTRA device. Our next step is to perform the FDA-required device verification testing, known as DV testing, for the combined handsets and single-use array required for our IND and BLA submissions.

推進 3107 是我們的主要關注點，我很高興地報告，我們已經解決了先前宣布的涉及 CELLECTRA 設備的一次性陣列組件的製造問題。我們的下一步是針對我們的 IND 和 BLA 提交所需的組合手機和一次性陣列執行 FDA 要求的設備驗證測試，即 DV 測試。

We now plan to begin submitting our BLA and the FDA's rolling submission process, as well as commencing our confirmatory trial and requesting priority review in mid 2025. With this timeline, we anticipate being able to complete rolling submission in the second half of the year to enable the FDA to accept our BLA filings before the end of the year.

我們現在計劃在 2025 年中期開始提交我們的 BLA 和 FDA 的滾動提交流程，以及開始我們的確認試驗並要求優先審查。根據這個時間表，我們預計能夠在下半年完成滾動提交，以便 FDA 能夠在年底之前接受我們的 BLA 申請。

Most importantly, we remain confident that if approved, 3107 could be the preferred non-surgical treatment for RRP for both patients and their physicians, a position that is strengthened by the year two and year three clinical data announced in December, and the detailed immunology data we published in February.

最重要的是，我們仍然相信，如果獲得批准，3107 將成為患者及其醫生首選的 RRP 非手術治療方法，而 12 月公佈的第二年和第三年臨床數據以及 2 月發布的詳細免疫學數據進一步證實了這一立場。

Mike will provide more detail in the call but in our retrospective trial of 3107, patient showed continued improvement in reduction in surgery after year one, with 50% meeting criteria for complete response in the second 12-month period or year two, meaning they were free. Overall, the mean number of surgeries across the patient population continue to decrease into year three.

Mike 將在電話中提供更多細節，但在我們對 3107 的回顧性試驗中，患者在第一年後手術減少的情況持續改善，其中 50% 的患者在第二個 12 個月或第二年達到完全緩解的標準，這意味著他們是自由的。總體而言，患者群體的平均手術次數在第三年持續減少。

The ongoing efficacy was observed but also supported by the immunology data published in Nature Communications, demonstrating the ability of 3107 to drive an antiviral immune response in airway tissue that correlated with a reduced or eliminated need for surgery. We also published the full safety and efficacy data set for the completed Phase 1, 2 trial, which shows that the administration of 3107 was well tolerated.

《自然通訊》雜誌發表的免疫學數據不僅觀察到了持續的療效，也支持了該藥的療效，證明了 3107 能夠驅動呼吸道組織中的抗病毒免疫反應，這與減少或消除手術需求有關。我們也發布了已完成的 1、2 期試驗的完整安全性和有效性數據集，該數據集顯示 3107 的給藥耐受性良好。

In summary, 3107 offers significant and durable clinical benefits, tolerability, and a simple patient-centric dosing regimen that does not require scoping or surgery during the dosing window -- all of which we believe could be compelling advantages once on the market.

總而言之，3107 具有顯著而持久的臨床益處、耐受性和簡單的以患者為中心的給藥方案，在給藥窗口期間不需要進行範圍界定或手術——我們相信，一旦上市，所有這些都可能成為引人注目的優勢。

While our immediate focus is on advancing 3107, I'm also pleased to provide an important update from our work on next generation DNA medicines. Together with our partners, we recently announced topline interim results from an ongoing Phase 1 trial with our DNA-encoded monoclonal antibody technology, which we call DMAb.

雖然我們目前的重點是推進 3107，但我也很高興提供我們在下一代 DNA 藥物研究方面的重大進展。我們最近與合作夥伴一起宣布了正在進行的 DNA 編碼單株抗體技術（我們稱之為 DMAb）的第 1 階段試驗的中期結果。

This proof of concept trial involved two DMAbs targeting SARS-CoV-2 and showed that they can be durably and simultaneously produced in humans at biologically relevant levels. We believe this technology has the potential to overcome some of the biggest challenges with traditional recumbent monoclonal antibodies and could also transform treatments for a broad range of diseases by enabling long-term in vivo production of therapeutic antibodies or other proteins.

這項概念驗證試驗涉及兩種針對 SARS-CoV-2 的 DMAb，並表明它們可以在生物學相關水平上在人體中持久且同時產生。我們相信這項技術有可能克服傳統單株抗體所面臨的一些最大挑戰，並且還可以透過實現治療性抗體或其他蛋白質的長期體內生產來改變多種疾病的治療方法。

Now, I'll turn it over to Mike for some additional insights on our progress, a new date on 3107 Mike?

現在，我將把問題交給 Mike，請他針對我們的進展發表一些額外的見解，3107 Mike 有新的日期嗎？

Thank you, Jackie. As Jackie mentioned, we have made tremendous progress towards our primary goal, submitting our BLA for 3107. We have now completed the drafting of all non-device modules, including non-clinical, clinical, and CMC modules.And after extensive testing and internal quality sign off, we have resolved the previously announced manufacturing issue involving the single-use array component of the CELLECTRA device.

謝謝你，傑基。正如 Jackie 所說，我們在實現主要目標方面取得了巨大進展，即提交 3107 的 BLA。我們現在已經完成了所有非設備模組的起草，包括非臨床、臨床和 CMC 模組。並且經過廣泛的測試和內部品質簽署確認後，我們已經解決了先前宣布的涉及 CELLECTRA 設備的一次性陣列組件的製造問題。

To resolve the issue, our device teams strengthened key components, reduced stress on breakage areas, and refined the production process for the plastic molded part of the array. We have tested the new array under similar testing to conditions to when the issue was first identified and have not been able to reproduce the breakage, which gives us great confidence that the modifications have resolved the issue.

為了解決這個問題，我們的設備團隊加強了關鍵零件，減少了破損區域的壓力，並改進了陣列塑膠成型部分的生產流程。我們已經在與首次發現問題時的條件類似的測試條件下測試了新陣列，並且無法重現故障，這使我們非常有信心，修改已經解決了問題。

We began manufacturing our new commercial grade arrays, which will now be utilized in the design verification testing, so we can move forward to completing our IND and BLA submissions.

我們開始製造新的商業級陣列，現在將用於設計驗證測試，因此我們可以繼續完成 IND 和 BLA 提交。

In addition, the full Phase 1, 2 clinical data and accompanying detailed immunology data were recently published in Nature Communications. These data further support the T-cell mechanism of action for 3107, which underpins the efficacy results we've seen.

此外，完整的1、2期臨床數據和隨附的詳細免疫學數據最近在《自然通訊》上發表。這些數據進一步支持了 3107 的 T 細胞作用機制，這為我們所看到的療效結果奠定了基礎。

We also announced some very exciting clinical durability data, showing that patients treated with 3107 continue to show further reduction in the need for surgery to manage their disease in the second and third year.

我們也發表了一些非常令人興奮的臨床耐久性數據，顯示接受 3107 治療的患者在第二年和第三年對手術治療疾病的需求進一步減少。

This data will be the subject of an oral presentation at the combined Otolaryngology Spring Meeting to be held in New Orleans this May 1 -- one of the most frequented meetings by our target physicians treating RRP.

這些數據將成為 5 月 1 日在新奧爾良舉行的聯合耳鼻喉科春季會議上口頭報告的主題——這是我們治療 RRP 的目標醫生最常參加的會議之一。

We've also made important progress in preparing for our Phase 3 confirmatory trial. As a reminder, this will be a randomized placebo controlled trial enrolling patients, with three or more surgeries in the prior year conducted at approximately 20 sites at major US medical centers. This progress to date will enable us to enroll in a timely manner following submission of our updated IND.

我們在準備第三階段確認試驗方面也取得了重要進展。提醒一下，這將是一項隨機安慰劑對照試驗，招募在過去一年中在美國主要醫療中心的約 20 個地點進行過三次或三次以上手術的患者。迄今為止的進展將使我們能夠在提交更新的 IND 後及時註冊。

I'd like to spend some time now discussing the new data. As it paints a compelling product profile that strengthens our belief that 3107 could be the preferred product for RRP patients and their physicians,

現在我想花點時間討論一下新數據。由於該產品具有引人注目的產品特性，讓我們更加堅信 3107 可能是 RRP 患者及其醫生的首選產品，

As a reminder, we completed a Phase 1, 2 open label trial of 3107 in patients who required at least two surgeries in the previous year for the removal of HPV-6, 11 related papillomas.

提醒一下，我們已完成 3107 例 1、2 期開放標籤試驗，這些患者在前一年需要接受至少兩次手術以切除 HPV-6、11 相關乳頭狀瘤。

It's important to note that based on our understanding of the risk and cost to the patient of every single surgery, every surgery performed after day zero was counted against the efficacy end point in our trial where we followed the patients for 12 months.

值得注意的是，根據我們對每次手術對患者的風險和成本的了解，在我們對患者進行 12 個月的隨訪的試驗中，零天後進行的每次手術都計入療效終點。

We then conducted RRP-002, a retrospective trial in which we were able to collect data on 28 of the original 32 patients to assess the longer-term treatment effect with a medium follow up of 2.8 years. RRP is a chronic, often lifelong disease, and duration of efficacy is clearly important.

隨後，我們進行了回顧性試驗 RRP-002，收集了最初 32 名患者中的 28 名患者的數據，以評估長期治療效果，中位追蹤期為 2.8 年。RRP 是一種慢性、常常是終身疾病，因此療效持續時間顯然非常重要。

Here we dive into the 002 data, looking at the longer-term efficacy results we observed in the trial. We were very pleased to see that patients continue to show improvement into years two and three following their initial dosing regimen. In fact, the complete response rate increased to 50% for the second 12-month period when evaluated at the end of year two.

在這裡，我們深入研究 002 數據，查看我們在試驗中觀察到的長期療效結果。我們非常高興地看到，患者在初始給藥方案後的第二年和第三年繼續表現出改善。事實上，第二年末的評估顯示，第二個 12 個月的完全回應率增加到了 50%。

We also saw the overall response rate, that is the number of patients that had 50% to 100% fewer surgeries compared to their pre-treatment baseline, increased from 72% in the first 12-month treatment period or year one to 86% for the second 12-month period or year two.

我們也看到整體反應率，即與治療前相比手術次數減少 50% 至 100% 的患者數量，從第一個 12 個月治療期或第一年的 72% 增加到第二個 12 個月治療期或第二年的 86%。

When you look at this in terms of the average or mean number of surgeries this patient group faced, it reduced by more than half from a mean of 4.1 surgeries per year prior to treatment to a mean of 1.7 surgeries at the end of year one, and then reduced further by the end of year two to a mean of 0.9 surgeries. Across the population of patients treated with 3107, this is a reduction of greater than 75% following the initial treatment regimen alone.

如果從該患者群體面臨的平均手術次數來看，則從治療前每年平均 4.1 次手術減少了一半以上，到第一年年底平均 1.7 次手術，然後到第二年年底進一步減少到平均 0.9 次手術。在接受 3107 治療的患者群體中，僅在初始治療方案後，這一減少量就超過了 75%。

However, one of the core strengths of our DNA medicines platform is the ability to administer additional doses to continue to drive and amplify strong T cell-based immune responses without having to worry about the impact of an anti-vector response.

然而，我們的 DNA 藥物平台的核心優勢之一是能夠施用額外的劑量以繼續驅動和放大強大的基於 T 細胞的免疫反應，而不必擔心抗載體反應的影響。

Looking again at the mean surgeries per year across the population, we saw a significant decrease in the year following treatment and then a further decrease in the second 12-month period or year two.

再次查看整個人群每年的平均手術次數，我們發現治療後的一年內手術次數顯著下降，然後在第二個 12 個月或第二年內進一步下降。

In year three, the improvement seems to be holding steady. And what we would like to be able to do is consider a longer term treatment strategy that supports both the maintenance of that complete or partial response and potentially extending clinical improvement, including the potential for non-responders to mount a clinical response.

第三年，這種改善似乎保持穩定。我們希望能夠考慮一種長期治療策略，既支持維持完全或部分反應，又可能延長臨床改善時間，包括無反應者產生臨床反應的可能性。

We have published data from a similar DNA medicine that targeted the E6 and E7 antigens of HPV-16 and 18 that demonstrated we were able to augment the CD8 T cell responses with a single additional dose.

我們已經發表了針對 HPV-16 和 18 的 E6 和 E7 抗原的類似 DNA 藥物的數據，證明我們能夠透過單次額外劑量增強 CD8 T 細胞反應。

Given after completion of the primary treatment course when compared to pre-dose levels, this further increase in cytotoxic T cells supports the potential of extending the duration and improving upon the already excellent clinical response that we have seen to date. Every surgery matters to patients and our vision for INO-3107 is to further minimize or eliminate future surgeries for all RRP patients.

與給藥前水平相比，完成主要治療療程後細胞毒性 T 細胞的進一步增加支持了延長治療持續時間和改善我們迄今為止看到的已經很出色的臨床反應的潛力。每一次手術對患者來說都很重要，我們對 INO-3107 的願景是進一步減少或消除所有 RRP 患者未來的手術。

As I said earlier, the immunology data we've recently published becomes important here, as it underpins the mechanism of action of 3107 and how we believe treatment is providing the favorable efficacy results we observed.

正如我之前所說，我們最近發表的免疫學數據在這裡變得重要，因為它支撐了 3107 的作用機制以及我們如何相信治療提供了我們觀察到的有利療效結果。

First, in our analysis, we found that all the patients were generating the right kind of antiviral immune responses to fight HPV, specifically, antigen-specific cytotoxic T cells. And then we saw that these T cells really got where they needed to go, traveling from the blood into the airway and papilloma tissue. Once they were in the airway tissues, they created an antiviral immune response which we believe is responsible for reducing or eliminating the need for surgery by eradicating HPV infected cells.

首先，在我們的分析中，我們發現所有患者都產生了正確的抗病毒免疫反應來對抗 HPV，具體來說是抗原特異性細胞毒性 T 細胞。然後我們發現這些 T 細胞確實到達了它們需要去的地方，從血液進入呼吸道和乳頭狀瘤組織。一旦它們進入呼吸道組織，它們就會產生抗病毒免疫反應，我們認為，透過消滅 HPV 感染細胞，可以減少或消除手術的需要。

I would also like to note that while other investigators have suggested that multiple factors such as high viral loads or neutrophil infiltration in the papilloma microenvironment can be barriers to immunotherapy treatment of RRP, we didn't see any such factors impacting the efficacy we observed in the trial.

我還想指出，雖然其他研究人員認為乳頭狀瘤微環境中的高病毒量或嗜中性球浸潤等多種因素可能是 RRP 免疫療法治療的障礙，但我們並沒有發現任何此類因素會影響我們在試驗中觀察到的療效。

While all patients were generating the right kind of immune response, in our non-responders, this response wasn't as large and tended to decrease faster than in our responders, which again is why we believe continued treatment may improve clinical outcomes in these patients.

雖然所有患者都產生了正確的免疫反應，但對於無反應的患者來說，這種反應並不大，而且往往比有反應的患者下降得更快，這也是我們相信持續治療可能會改善這些患者臨床結果的原因。

Overall, our immunology data provide a clear demonstration of the mechanism of action behind INO-3107, showing that it is doing exactly what is needed to treat the underlying HPV infection that causes RRP.

總體而言，我們的免疫學數據清楚地證明了 INO-3107 背後的作用機制，表明它正在發揮治療導致 RRP 的潛在 HPV 感染所需的作用。

To wrap up, I want to provide some additional detail on our next steps for 3107. Now that we have resolved the array issue, we have commenced the manufacturing of the new arrays which we will subsequently age condition and utilize in the conduct of the FDA-required design verification or DV testing process, which we anticipate will be completed in the first half of this year. This testing is required to update the IND before we can dose patients in our confirmatory trial and is also part of the last remaining module of our BLA package we need to complete.

最後，我想就 3107 的下一步提供一些額外的細節。現在我們已經解決了陣列問題，我們已經開始製造新的陣列，隨後我們將對其進行老化條件並用於 FDA 要求的設計驗證或 DV 測試過程，我們預計將在今年上半年完成。在我們能夠在確認性試驗中為患者給藥之前，需要進行此項測試以更新 IND，這也是我們需要完成的 BLA 包的最後一個模組的一部分。

We plan to request rolling submission and priority review of [that] BLA. And if FDA agrees, we will begin submitting our modules in mid 2025 and complete the full submission three to four months later with the goal of having the FDA accept our complete BLA for filing by the end of the year.

我們計劃要求對 BLA 進行滾動提交和優先審查。如果 FDA 同意，我們將在 2025 年中期開始提交模組，並在三到四個月後完成全面提交，目標是讓 FDA 在年底前接受我們的完整 BLA 以供提交。

Once the entire BLA is submitted, we plan to finalize our long-term dosing study strategy and submit a proposed protocol to the FDA to support a supplemental BLA in the future. We also look forward to commencing onboarding of our field medical science liaison team and presenting this exciting data package at several upcoming conferences this spring, including the US-based National HPV Conference, the European ALS Congress, and COSM, among others listed on the slide.

一旦提交了整個 BLA，我們計劃最終確定我們的長期劑量研究策略，並向 FDA 提交一份擬議方案，以支持未來的補充 BLA。我們也期待開始組建我們的現場醫學科學聯絡團隊，並在今年春季即將舉行的幾個會議上展示這個令人興奮的數據包，其中包括美國國家 HPV 會議、歐洲 ALS 大會和 COSM 以及幻燈片上列出的其他會議。

With that, I will now send over to our Chief Commercial Officer Steve Egge, for an update on our commercial efforts. Steve?

現在，我將向我們的首席商務官史蒂夫·埃格 (Steve Egge) 匯報我們商業努力的最新進展。史蒂夫？

Thanks Mike. I'd like to build on the 3107 data Mike shared by reviewing why our work on RRP is so important, what the market looks like, why 3107 could be the product of choice for patients and providers, and what we're doing to prepare for potential commercialization.

謝謝邁克。我想基於 Mike 分享的 3107 數據，回顧我們在 RRP 方面的工作為何如此重要、市場狀況如何、為什麼 3107 可能是患者和供應商的首選產品，以及我們為潛在的商業化做了哪些準備。

For those new to our work, RRP is a rare HPV-related disease that affects around 14,000 people in the US. It's characterized by wart-like growths called papilloma that grow in the respiratory tract and can cause difficulty speaking, swallowing, and breathing, and repeated surgery is the standard of care today.

對於我們工作的新人來說，RRP 是一種罕見的 HPV 相關疾病，影響美國約 14,000 人。它的特徵是在呼吸道中生長出類似疣的腫塊，稱為乳頭狀瘤，可導致說話、吞嚥和呼吸困難，重複手術是當今的標準治療方法。

Every one of these surgeries matters to patients because every surgery poses a risk of irreversible damage to the vocal cords and carries costs, including the financial expense, but more importantly, the significant time and stress of preparing for and recovering from each surgery. Patients and their providers want a non-surgical option for RRP that addresses the underlying disease and that ultimately helps them avoid additional surgeries.

每一次手術對患者來說都很重要，因為每次手術都有可能對聲帶造成不可逆轉的損傷，而且需要花費大量金錢，包括經濟費用，但更重要的是，每次手術的準備和恢復都需要大量的時間和壓力。患者及其提供者希望有一個非手術的 RRP 選項，可以解決潛在疾病，並最終幫助他們避免額外的手術。

We designed 3107 with the patient experience in mind, and we believe it has the potential to become the preferred treatment option for RRP based on the efficacy and tolerability results we've observed to date, as well as the simple patient-centric treatment regimen.

我們在設計 3107 時充分考慮了患者的體驗，我們相信根據迄今為止觀察到的療效和耐受性結果，以及簡單的以患者為中心的治療方案，它有可能成為 RRP 的首選治療方案。

As Mike discussed, not only do we observe favorable efficacy results in patients treated with 3107, we saw continued improvement into the second 12-month period or year two for both complete and overall response rates. 3107 was well tolerated in the trial, and there were no discontinuations.

正如 Mike 所討論的，我們不僅觀察到接受 3107 治療的患者的良好療效結果，而且我們還看到在第二個 12 個月或第二年，完全緩解率和整體緩解率都持續改善。 3107 在試驗中耐受性良好，且沒有停藥的情況。

And finally, 3107 offers a simple patient-centric treatment regimen that does not require additional potentially unnecessary scoping and procedures during the treatment window. And finally, 3107 offers office-based administration without the need for referral, a preference that many physicians shared with us in market research.

最後，3107 提供了一種簡單的以患者為中心的治療方案，不需要在治療期間進行額外的可能不必要的檢查和程序。最後，3107 提供辦公室管理，無需轉診，這是許多醫生在市場調查中與我們分享的一種偏好。

We've shared a few other insights on this slide from that research, reinforcing our belief in the strength of 3107's product profile. One laryngologist told us, the complete response rate of 50% is good, but a 50% to 100% reduction in surgeries in 8 out of 10 patients is the most compelling.

我們在這張投影片上分享了研究的一些其他見解，增強了我們對 3107 產品實力的信心。一位喉科醫生告訴我們，50% 的完全緩解率已經很好了，但最令人信服的是，10 個患者中有 8 個的手術量減少 50% 到 100%。

When laryngologists review our data, they quickly move to think about how they would describe the product to their patients. And they indicate they like being able to say the vast majority of patients see significant benefit from treatment. Likewise, both the tolerability profile and simple patient-focused treatment regimen were very well received by laryngologists who are currently treating RRP patients.

當喉科醫生審查我們的數據時，他們很快就開始思考如何向患者描述該產品。他們表示，他們很高興能夠說絕大多數患者都從治療中獲得了顯著的益處。同樣，耐受性概況和簡單的以患者為中心的治療方案也受到目前治療 RRP 患者的喉科醫生的一致好評。

Moving on, I'd like to share just a few updates on our commercial launch preparations. Since last quarter, we've made significant progress, including developing our distribution channel strategy and identifying channel partners, developing our initial pricing strategy, and completing targeting, segmentation, and product-positioning work to establish positive differentiation.

接下來，我想分享一些關於我們商業發布準備的最新進展。自上個季度以來，我們取得了重大進展，包括制定分銷通路策略和確定通路合作夥伴、制定初步定價策略，以及完成定位、細分和產品定位工作以建立積極的差異化。

We're currently developing our go-to-market model and planning a further build out of the commercial organization. Given the RRP market is highly concentrated, with the majority of RRP patients treated by relatively few laryngologists, we believe we will need a small and efficient field force footprint.

我們目前正在開發我們的市場進入模式並計劃進一步擴大商業組織。鑑於 RRP 市場高度集中，大多數 RRP 患者由相對較少的喉科醫生治療，我們認為我們需要一個小型而高效的現場團隊。

There's still a lot of work ahead, but I'm energized by what we've built so far and look forward to providing an update on our progress next quarter. With that, I will turn it back to Jackie.

未來還有大量工作要做，但我對我們目前的成果感到十分振奮，並期待下個季度提供我們進展的最新情況。說完這些，我就把事情轉交給 Jackie。

Thanks, Steve. While 3107 is at the forefront of our work, we are excited about the opportunities to leverage the strength of our platform across the pipeline, including what we see as the next generation of DNA medicine technology.

謝謝，史蒂夫。雖然 3107 是我們工作的重點，但我們對能夠在整個研發過程中發揮我們平台優勢的機會感到興奮，其中包括我們所看到的下一代 DNA 藥物技術。

Monitoring the power of in vivo protein production and enabling the body to generate its own disease fighting tools is a key strength of our DNA medicine platform. And our DMAb technology leverages that strength in a novel way.

監測體內蛋白質生產的能力並使身體能夠產生自己的抗病工具是我們 DNA 醫學平台的關鍵優勢。我們的 DMAb 技術以新穎的方式利用了這項優勢。

Using our proprietary gene sequence optimization technology, we can create precisely designed DNA plasmids that encodes for specific monoclonal antibodies. These plasmids, also called the [TMA] can then be delivered directly into muscle cells in the arm using our CELLECTRA delivery system.

利用我們專有的基因序列優化技術，我們可以創建精確設計的編碼特定單株抗體的 DNA 質粒。這些質粒（也稱為 [TMA]）可以透過我們的 CELLECTRA 輸送系統直接輸送到手臂的肌肉細胞。

The heavy and light chain proteins that make up the DMAbs are produced and then assembled into functional antibodies within the muscle cells and are then secreted into the blood where they can circulate within the body. This contrasts with conventional monoclonal antibodies, which are manufactured in in vitro systems and then need to be administered through regular effusion or injection.

組成 DMAb 的重鏈和輕鏈蛋白質在肌肉細胞內產生並組裝成功能性抗體，然後分泌到血液中並在體內循環。這與傳統的單株抗體形成對比，傳統的單株抗體是在體外系統中製造的，然後需要透過常規滲出或註射進行給藥。

We recently announced topline interim clinical data from an ongoing Phase 1 proof-of-concept trial evaluating DMAbs for COVID-19, led by the Wistar Institute in collaboration with AstraZeneca, the University of Pennsylvania, and Inovio. And funded by DARPA and JPO, this trial has provided the first clinical proof-of-concept that DMAbs can be durably and simultaneously produced inside the human body.

我們最近公佈了正在進行的 1 期概念驗證試驗的頂線中期臨床數據，該試驗評估了針對 COVID-19 的 DMAb，該試驗由 Wistar 研究所牽頭，與阿斯特捷利康、賓夕法尼亞大學和 Inovio 合作。該試驗由 DARPA 和 JPO 資助，提供了第一個臨床概念驗證，證明 DMAbs 可以在人體內持久且同時產生。

Specifically, we saw long lasting in vivo antibody production with DMAb levels remaining stable for 72 weeks in all participants who have reached that time point. No anti-drug antibodies or immune rejection of the DMAb was detected across approximately 1,000 blood samples, unlike other gene-based antibody delivery approaches.

具體來說，我們看到體內抗體的產生持續時間長，所有達到該時間點的參與者的 DMAb 水平在 72 週內保持穩定。與其他基於基因的抗體遞送方法不同，在大約 1,000 個血液樣本中未檢測到抗藥物抗體或對 DMAb 的免疫排斥。

And treatment was well tolerated, with the most common side effects being mild temporary injection site reactions such as pain and redness, and no serious adverse events related to study drugs. And we saw that the expressed DMAbs successfully balanced the SARS-CoV-2 Spike protein receptor binding domain, confirming functional activity through week 72.

且治療耐受性良好，最常見的副作用是注射部位出現輕微的暫時性反應，如疼痛和發紅，且沒有與研究藥物相關的嚴重不良事件。我們發現表達的 DMAb 成功平衡了 SARS-CoV-2 刺突蛋白受體結合域，證實了截至第 72 週的功能活性。

I also just want to point out that the panel on the right-hand side of the slide shows the representative data from one dose level cohort from the trial. The consortium plans to present its important clinical data in the first half of the year at various scientific conferences and has submitted a manuscript to a leading peer review journal which is currently available in preprint on Research Square.

我還想指出，幻燈片右側的面板顯示了試驗中一個劑量水平組的代表性數據。該聯盟計劃在今年上半年在各種科學會議上展示其重要的臨床數據，並已向領先的同行評審期刊提交了一份手稿，目前該手稿的預印本可在 Research Square 上查閱。

We believe this technology could have the potential to be a breakthrough that could overcome many of the challenges with traditional monoclonal antibody production with rapid manufacturing, low cost of production, temperature stable storage and distribution, and the ability to redose, DMAb technology could help expand use, reduce costs, and enable access and lows.

我們相信這項技術可能具有突破性的意義，可以克服傳統單株抗體生產中的許多挑戰，具有快速製造、低成本、溫度穩定的儲存和分配以及重複使用的能力，DMAb 技術可以幫助擴大使用範圍、降低成本並實現獲取和降低成本。

Importantly, unlike other delivery platforms, our DNA-based approach has demonstrated sustained antibody production without generating anti-drug antibodies, making it a potentially promising long-term solution for conditions requiring continuous therapeutic protein delivery.

重要的是，與其他遞送平台不同，我們的基於 DNA 的方法已證明能夠持續產生抗體而不會產生抗藥物抗體，這使其成為需要持續遞送治療性蛋白質的病症的潛在有希望的長期解決方案。

We see broad potential for this technology, and we and our partners at Wistar have been investigating the feasibility of DMAbs across multiple targets, mostly in a pre-clinical setting, from flu to HIV to cancers, and to the most recent clinical trial targeting COVID-19.

我們看到這項技術的廣泛潛力，我們和 Wistar 的合作夥伴一直在研究 DMAb 在多個目標上的可行性，主要是在臨床前環境中，從流感到愛滋病毒到癌症，以及最近針對 COVID-19 的臨床試驗。

I believe this is an excellent example of how we've been able to work through partnerships with non-diluted funding to advance our DNA medicines platform. We look forward to continuing working with our partners to complete the current Phase 1 trial and on future research, where we plan to explore a number of these broader applications for our technology for long-term therapeutic protein delivery.

我相信這是我們如何透過合作關係以非稀釋資金推進我們的 DNA 藥物平台的一個極好的例子。我們期待繼續與我們的合作夥伴一起完成目前的第一階段試驗和未來的研究，我們計劃探索我們的技術在長期治療蛋白質遞送方面的許多更廣泛的應用。

Moving on to the rest of our pipeline, you'll see here that we have two other novel technologies in the pre-clinical stage. DNA-launched nanoparticle or DLNP candidates addressing infectious diseases -- I'm following on from my comments on DMAb -- DNA-encoded protein replacements candidates or DPROT, addressing various diseases where disease is caused by missing or defective proteins. These fall into that next generation category of our technology, and we're very excited about what the future holds for these novel approaches.

繼續介紹我們其餘的產品線，您會看到我們還有另外兩項處於臨床前階段的新技術。DNA 發射奈米粒子或 DLNP 候選藥物可治療傳染病 - 我將繼續對 DMAb（DNA 編碼蛋白質替代候選藥物或 DPROT）發表評論，用於治療因蛋白質缺失或缺陷而引起的各種疾病。這些屬於我們技術的下一代類別，我們對這些新方法的未來發展感到非常興奮。

With regards to our [latest stage] pipeline, we're leveraging the opportunity to build on our extensive experience in HPV-related diseases and advancing plans for a Phase 3 trial to evaluate INO-3112 in combination with the FDA approved PD-1 inhibitor LOQTORZI as a treatment for local [reaching] advanced, high risk HPV-16 and 18 positive throat cancer.

關於我們的[最新階段]產品線，我們正在利用這個機會，利用我們在 HPV 相關疾病方面的豐富經驗，並推進 3 期試驗計劃，以評估 INO-3112 與 FDA 批准的 PD-1 抑製劑 LOQTORZI 聯合使用，用於治療局部[達到]晚期、高危險 HPV-16 和 18 陽性喉癌。

With the trial planned across both North America and Europe, we've discussed the trial design with FDA and most recently received some initial feedback from the European regulators on the trial design. We believe our current design will be sufficient to address those comments, and our next steps include finalizing the trial protocol and completing manufacture of the candidate.

由於該試驗計劃在北美和歐洲進行，我們已經與 FDA 討論了試驗設計，最近還收到了歐洲監管機構對試驗設計的一些初步回饋。我們相信我們目前的設計足以解決這些意見，我們的下一步包括最終確定試驗方案並完成候選藥物的製造。

We're advancing discussions on the design for a Phase 2 trial of INO-5401 newly diagnosed glioblastoma, and we look forward to advancing this and other promising candidates through collaboration and other potential strategic opportunities.

我們正在推進 INO-5401 新診斷膠質母細胞瘤 2 期試驗設計的討論，並期待透過合作和其他潛在策略機會推進該藥物和其他有前景的候選藥物的研究。

I will now turn this over to our Chief Financial Officer, Peter Kies, for a financial update. Peter?

現在我將把這個交給我們的財務長 Peter Kies 來報告財務最新情況。彼得？

Thanks, Jackie. Today I'd like to provide an overview of Inovio's financial results for the fourth quarter and full year of 2024. As Jackie noted at the start of our call, our primary goal is advancing INO-3107, being ready to begin the submission of our BLA in mid 2025, and ensuring that we have the resources to support this critical work.

謝謝，傑基。今天，我想概述 Inovio 2024 年第四季和全年的財務表現。正如 Jackie 在電話會議開始時所說，我們的主要目標是推進 INO-3107，準備在 2025 年中期開始提交 BLA，並確保我們有足夠的資源來支持這項關鍵工作。

To that effect, we raised more than $72 million in gross proceeds from two equity offerings in April and December of 2024 and from equity sales from our ATM.

為此，我們透過 2024 年 4 月和 12 月的兩筆股票發行以及 ATM 的股票銷售籌集了超過 7,200 萬美元的總收益。

We also continue to decrease operational spending with our total operating expenses dropping from $27.5 million in the fourth quarter of 2023 to $20.5 million in the fourth quarter of 2025. Our full year operational expenses decreased 22% from $144.8 million in 2023 to $112.6 million in 2024.

我們也持續減少營運支出，總營運支出從 2023 年第四季的 2,750 萬美元下降到 2025 年第四季的 2,050 萬美元。我們的全年營運費用從 2023 年的 1.448 億美元下降 22% 至 2024 年的 1.126 億美元。

Inovio's net loss for the fourth quarter of 2024 was $19.4 million, or $0.65 per share of basic and dilutive. And our total net loss for the full year of 2024 was $107.3 million, or $3.95 per share basic and dilutive.We finished the fourth quarter of 2024 with $94.1 million in, cash, cash equivalents, and short-term investments compared to $145.3 million as of December 31, 2023.

Inovio 2024 年第四季的淨虧損為 1,940 萬美元，即每股基本虧損和稀釋虧損 0.65 美元。我們 2024 年全年的總淨虧損為 1.073 億美元，或每股基本虧損和稀釋虧損 3.95 美元。截至 2024 年第四季度，我們的現金、現金等價物和短期投資為 9,410 萬美元，截至 2023 年 12 月 31 日為 1.453 億美元。

We estimate our cash runway to take us into the first quarter of 2026. This projection includes an operational net cash burn estimate of approximately $27 million for the first quarter of 2025. Historically, our first quarter operational net cash burn runs higher than other quarters. These cash projections -- this cash runway projections do not include any further capital raise activity that Inovio may undertake.

我們預計我們的現金流可以維持到 2026 年第一季。該預測包括 2025 年第一季約 2,700 萬美元的營運淨現金消耗估計。從歷史上看，我們第一季的營運淨現金消耗高於其他季度。這些現金預測—這些現金跑道預測不包括 Inovio 可能進行的任何進一步的融資活動。

As a result, you can find our full financial statements in this afternoon's press release, as well as in our Form 10-K filed with the SEC. And with that, I'll turn it back over to Jackie.

因此，您可以在今天下午的新聞稿中以及我們向美國證券交易委員會提交的 10-K 表中找到我們的完整財務報表。現在我將把話題轉回給 Jackie。

Thanks, Peter. I'd now like to open up the call to answer any questions you might have. Operator?

謝謝，彼得。我現在想開始電話會議來回答大家可能提出的任何問題。操作員？

(Operator Instructions) Roy Buchanan, Citizens.

（操作員指示）羅伊·布坎南，公民。

Hey, thanks for taking the questions. Glad to hear you're on track with 3107, had some -- I guess some details; let's start with 3107. So the BLA submission request, you need to meet with the FDA, or do you just request that in writing? And if you need to meet, have you requested that meeting?

嘿，感謝您回答這些問題。很高興聽到你對 3107 的進度很了解，我想有一些細節；讓我們從 3107 開始。那麼，BLA 提交請求，您需要與 FDA 會面，還是只是以書面形式提出請求？如果您需要開會，您是否已要求召開該會議？

Yeah, good question, Roy. Mike, do you want to take that?

是的，羅伊，你問得好。麥克，你想接受這個嗎？

Yeah, happily. So we actually held a pre-BLA meeting with the FDA prior to the single-use array breakage that we found and have now resolved. And at that time we actually had very good alignment with all the remaining modules. And so we -- as soon as we complete the device modules at BLA will be complete and as we talked about today, we plan to hopefully start rolling submission in the middle of next -- of this year, as all the other remaining modules are complete.

是啊，很開心。因此，在發現一次性陣列破損之前，我們實際上與 FDA 舉行了 BLA 前會議，目前我們已經解決了這個問題。當時我們實際上與所有剩餘的模組都進行了非常好的協調。因此，一旦我們完成 BLA 的設備模組，我們就完成了，正如我們今天談到的，我們計劃在明年年中開始滾動提交，因為所有其他剩餘的模組都已完成。

That's a request, yeah, we don't need to have another meeting.

這是請求，是的，我們不需要再開會了。

No more meeting, but we do need to request the rolling submission.

不再開會，但我們確實需要請求滾動提交。

Yeah, got it. Okay. And then, so for the stability test, is that maybe you said -- sorry I missed it, but is that a single test or do you need to repeat a whole battery of tests? And are you doing that yourself or is it a third party who conducts the tests?

嗯，明白了。好的。那麼，對於穩定性測試，也許您說過——抱歉我錯過了，但這是一個單獨的測試還是您需要重複一整套測試？這是您自己做的還是由第三方進行測試？

Yeah, that's a great question, Roy. So we need to repeat a number of the tests required for device verification or DV testing where we're testing the array in combination with the handset so we need to repeat a number of those different tests and we use an external testing house to do that.

是的，這是一個很好的問題，羅伊。因此，我們需要重複進行設備驗證或 DV 測試所需的許多測試，我們將陣列與手機結合進行測試，因此我們需要重複進行許多不同的測試，並且我們使用外部測試機構來進行這些測試。

So we've previously worked extensively with the testing house. They're great partners, but we do need to do that externally. And there's also some external certification that's required as part of this process that goes into our BLA as well. Mike, anything to add that?

我們之前曾與測試機構進行過廣泛的合作。他們是很好的合作夥伴，但我們確實需要在外部做到這一點。此流程還需要一些外部認證，這些認證也包含在我們的 BLA 中。麥克，還有什麼要補充嗎？

No, I think you've covered all the major points.

不，我認為你已經涵蓋了所有要點。

Okay, great. Then maybe on the DMAb, I thought the data in the publication is pretty compelling, clearly differentiated from mRNA, even self-amplifying, RNAs in terms of durability.

好的，太好了。那麼也許在 DMAb 上，我認為出版物中的數據非常引人注目，在耐用性方面與 mRNA 甚至自擴增的 RNA 有明顯區別。

But I didn't see anything in the publication about half-life. Seems like it's clearly longer than even the extended half-life antibodies that you're expressing. Do you have any sense of what the half-life from the DNA constructs themselves might be in people?

但我在出版物中沒有看到有關半衰期的任何內容。看起來它顯然比您表達的延長半衰期抗體還要長。您是否知道 DNA 結構本身在人體內的半衰期是多久？

Yeah. I'm not sure if we've released all of that data yet. Roy is part of the publication. What we do have in the publication is some details of modifications we've made for these particular monoclonals to extend life. So happy to follow up with you after the call on the specific details [of both].

是的。我不確定我們是否已經發布了所有數據。羅伊 (Roy) 是該出版物的一部分。我們在出版物中確實介紹了我們針對這些特定單株抗體所做的延長壽命的修改的一些細節。很高興在通話結束後與您討論具體細節[兩者皆有]。

Okay, great. And then Jackie, I know you mentioned some, other -- a wide range of potential applications for the technology and the publication mentions GLP-1, for example. Do you have any -- anything you can disclose today about potential programs over the next 24 months or so? Thanks.

好的，太好了。然後 Jackie，我知道您提到了一些其他的東西——該技術的廣泛潛在應用，例如出版物中提到了 GLP-1。您今天可以透露有關未來 24 個月左右的潛在計劃的任何資訊嗎？謝謝。

Yeah. I think first of all I would say we were really excited to see the level of functional antibody production that we saw over such a long time period and the fact that we didn't see any anti-drug antibodies at all coming up, so we were really excited about that.

是的。我想首先要說的是，我們真的很高興看到在如此長的時間內我們看到的功能性抗體產生水平，以及我們根本沒有看到任何抗藥性抗體出現的事實，所以我們對此感到非常興奮。

On today's call, we shared with you a broad range of other targets that previously worked on and are working on. And we hope to provide further updates on those targets in due course, but we're really excited by the power of this technology and the level that we're producing these antibodies at the moment is biologically relevant and the levels needed for a wide range of targets so we're really excited by that.

在今天的電話會議上，我們與大家分享了我們之前和正在進行的一系列其他目標。我們希望在適當的時候對這些目標提供進一步的更新，但我們對這項技術的威力感到非常興奮，我們目前生產這些抗體的水平在生物學上是相關的，並且達到了廣泛目標所需的水平，所以我們對此感到非常興奮。

Yeah, okay. Sounds good thank you. Thanks, Roy.

嗯，好的。聽起來不錯，謝謝。謝謝，羅伊。

Jay Olson, Oppenheimer.

傑伊奧爾森、奧本海默。

Oh hey, congrats on resolving the manufacturing issues with the CELLECTRA device and thank you for providing this update.

哦，嘿，恭喜您解決了 CELLECTRA 設備的製造問題，感謝您提供此更新。

We had a question about the timeline for testing and validation of the new manufacturing process and how long it takes for validation before including the new manufacturing information in your filing package?

我們對新製造流程的測試和驗證時間表有疑問，以及在將新製造資訊納入文件包之前需要多長時間進行驗證？

Yeah. Sure, Jay. So first of all, I'm just really thrilled and delighted that we've fixed the snapframe part, the single-use array component of the device that broke.

是的。當然，傑伊。首先，我真的很興奮和高興我們已經修復了 snapframe 部分，即該設備損壞的一次性陣列組件。

The process did take a little longer than we initially expected as we needed to make some design changes to the part, which also required us to improve the actual molding process. Now that we've got this behind us, we've started manufacturing the new arrays. And we plan to start device verification testing very soon, and we anticipate we're going to complete all of that in the first half of this year.

這個過程確實比我們最初預期的要長一點，因為我們需要對零件做一些設計更改，這也要求我們改進實際的成型過程。現在我們已經完成了這項工作，並開始製造新的陣列。我們計劃很快開始設備驗證測試，預計今年上半年完成所有測試。

As Mike said earlier on in the call, once this process is near completion, we'll reach out to the FDA and request rolling submission of the BLA since we have all of the other modules completed and ready for submission.

正如 Mike 在通話中早些時候所說的那樣，一旦這個過程接近完成，我們將聯繫 FDA 並要求滾動提交 BLA，因為我們已經完成所有其他模組並準備好提交。

And then once that's granted, we expect to begin submitting the modules in mid-year and anticipate being able to complete the submission three to four months later with the expectation that FDA will accept our full BLA for review prior to the end of the year.

一旦獲得批准，我們預計將在年中開始提交模組，並預計能夠在三到四個月後完成提交，同時預期 FDA 將在年底之前接受我們的完整 BLA 進行審查。

Okay, great. Thank you so much for that detailed explanation and maybe just one follow up question. Do you need to initiate the confirmatory study before the BLA submission?

好的，太好了。非常感謝您如此詳細的解釋，也許我還有一個後續問題。您是否需要在提交 BLA 之前啟動確認性研究？

So we do need to initiate the confirmatory trial before the BLA submission, but we've made really good progress in terms of doing that. And Mike, do you want to jump in here?

因此，我們確實需要在提交 BLA 之前啟動確認試驗，但我們在這方面已經取得了良好的進展。麥克，你想加入進來嗎？

Yeah, absolutely. So I mean we've previously talked that we have identified the majority of the sites. We've actually advanced contracts and actually have IRB approvals at several sites. So the whole reason the FDA usually ask you to commence that trial is so that they can feel confident that you are going to meet the commitment to complete the study.

是的，絕對是如此。所以我的意思是我們之前已經談過我們已經確定了大多數站點。我們實際上已經簽訂了合同，並且在多個站點獲得了 IRB 批准。因此，FDA 通常要求您開始該試驗的全部原因是，這樣他們就可以確信您將履行完成研究的承諾。

We'll be very easily able to demonstrate to the FDA the seriousness we're approaching the study, and the fact that we want to complete enrollment and the study as quickly as possible.

我們將能夠非常輕鬆地向 FDA 證明我們對這項研究的認真態度，以及我們希望盡快完成招募和研究的事實。

Great, that's fantastic news. Thanks again for taking the questions and congrats on all the progress.

太好了，這真是個好消息。再次感謝您回答問題，並祝賀您取得的所有進展。

Sudan Loganathan, Stephens.

蘇丹·洛加納坦，史蒂芬斯。

Hi, good afternoon and thank you for giving this update. And congrats again on the great progress here with this CELLECTRA device and resolving those issues. My question is on that topic, just curious to hear your take on, aside from the -- in -- of the confirmatory trial needed to submit for the BLA.

大家下午好，感謝您提供最新消息。再次恭喜 CELLECTRA 設備取得巨大進展並解決了這些問題。我的問題是關於這個主題的，只是好奇想聽聽你的看法，除了提交 BLA 所需的確認試驗之外。

Is there anything else holding you back from just trying to submit the non-device component modules of the BLA now and starting the rolling process that way versus waiting a few more months to start submitting everything?

還有什麼因素阻礙您現在嘗試提交 BLA 的非設備組件模組並以此方式啟動滾動流程，而不是等待幾個月才開始提交所有內容？

Yeah, that's that's a really good question, Sudan. So we have, as we said, we have all of the other modules ready to go.

是的，蘇丹，這是一個非常好的問題。正如我們所說，我們已經準備好所有其他模組。

FDA normally, once you've started rolling submission, FDA normally like you to submit all of your modules in a three to four month time frame, but it is a discussion that we can have with the FDA as to when when we can start rolling submissions.

FDA 通常希望您在三到四個月的時間內提交所有模組，但我們可以與 FDA 討論何時開始滾動提交。

And I think the important thing is that we start our DV testing, have made good progress on the DV testing before we set that end timeline for when we're going to deliver all of the modules to the BLA. So I think the guidance that we're providing at the moment is that we're going to start rolling submission mid year and we expect to complete that within three to four months.

我認為重要的是我們開始了 DV 測試，並且在設定將所有模組交付給 BLA 的最終時間表之前在 DV 測試方面取得了良好的進展。因此，我認為我們目前提供的指導是，我們將在年中開始滾動提交，並預計在三到四個月內完成。

But obviously, we're going to try and accelerate things as much as possible. Every day matters to our occupations, and we're very conscious of that.

但顯然，我們會盡力加快進程。每一天對我們的職業都很重要，我們非常清楚這一點。

Got it. No, thank you for that. And quickly, just hopefully jog my memory better. Was the DV testing where the initial -- the breakage of the [electrode] device component was discovered previously, or did -- yeah -- were you able to get to the DV testing point last time, you know, before?

知道了。不，謝謝你。並且很快地，希望能更好地喚醒我的記憶。DV 測試中是否曾發現過最初的——[電極] 設備組件損壞，或者——是的——您上次能夠到達 DV 測試點嗎，以前呢？

Before? Yeah, I mean, last time we were pretty far through our DV testing when I believe we identified the issue with the single use array. Mike, do you want to add any detailer?

前？是的，我的意思是，上次我們在 DV 測試中已經取得了很大進展，我相信我們已經發現了一次性陣列的問題。麥克，你想添加任何細節嗎？

Yeah, so I mean we identified the issue following the age conditioning. And we have actually -- with the -- as part of the progress that we made and how we developed this -- we actually have already aged some of the arrays in a similar manner and actually performed the testing. So we really are confident that we will -- we've resolved the issue.

是的，所以我的意思是我們根據年齡條件確定了這個問題。而且我們實際上 - 作為我們所取得的進展的一部分以及我們如何開發這一點 - 我們實際上已經以類似的方式老化了一些陣列並實際進行了測試。所以我們真的有信心——我們已經解決了這個問題。

We do, however, have to actually repeat the formal aging and the formal testing once we have actually signed off the fix, which we have done and we've started manufacturing those sort of commercial grade arrays, but we do not expect to see any issues going forward with the array.

然而，一旦我們實際簽署了修復方案，我們確實必須重複正式老化和正式測試，我們已經完成了這項工作，並已開始製造這類商業級陣列，但我們預計陣列在未來不會出現任何問題。

Got it. Thank you. And just really quick one last one. Just given the context for the RRP patients often require multiple surgeries per year and just essential healthcare costs and risks, associated with that, as you know.

知道了。謝謝。最後一個非常快的。鑑於 RRP 的背景，患者通常每年需要多次手術，並且需要承擔與此相關的基本醫療費用和風險，如您所知。

Has there been any health economists or [pair] of research, conducted yet on the potential pricing? Or the advantages of therapeutics such as 3107 that would, in savings for the healthcare, providers, and or the healthcare facilities in the system in general, or is that something that could come maybe after approval, once we kind of get a better idea of pricing just kind of curious what, if that's anything that's been done on your end, on that?

是否有任何健康經濟學家或[一對]研究對潛在定價進行研究？或者 3107 等治療方法的優勢在於，可以為整個系統的醫療保健、服務提供者和/或醫療保健設施節省開支，還是說這可能是在獲得批准後，一旦我們對定價有了更好的了解，只是有點好奇，如果您在這方面做了什麼的話？

Yeah, Steve, do you want to take that one?

是的，史蒂夫，你想拿那個嗎？

Yeah, sure. So thanks for the question. So we've done a fair amount of research with payers where we reviewed product profile, reviewed budget impact models, and talked to them about kind of price ranges. This is rare disease. We do expect rare disease pricing, so kind of, what we've shared is that could be a pretty big range -- anywhere from $200,000 to $2 million -- a year.

是的，當然。感謝您的提問。因此，我們對付款人進行了大量的研究，包括審查了產品概況、審查了預算影響模型，並與他們討論了價格範圍。這是一種罕見的疾病。我們確實預計了罕見疾病的定價，所以我們所分享的是，該定價範圍可能相當大——每年從 20 萬美元到 200 萬美元不等。

But one analogy that we look at that's pretty close, like we've referenced it before the Ocivvio from Spring Works Therapeutics. It's a product for desmoid tumors, kind of the first medical therapy. The standard of care kind of prior to that launching was repeated surgeries.

但我們看到的一個類比非常接近，就像我們在 Spring Works Therapeutics 的 Ocivvio 之前提到的那樣。這是一種治療纖維瘤的產品，屬於第一種藥物療法。在推出該技術之前，標準的治療方法是重複手術。

They're in the the price range of 360,000 per year. That's kind of a price that we've referenced, and the feedback that we've gotten from payers is that you know that kind of rare disease pricing range is very acceptable to them, so we don't expect any issues kind of with rare disease pricing if that helps.

它們的價格在每年 360,000 左右。這是我們參考過的價格，而且我們從付款人那裡得到的反饋是，這種罕見疾病的定價範圍對他們來說是非常可以接受的，所以如果有幫助的話，我們預計罕見疾病的定價不會出現任何問題。

Yeah, that's great. Thank you again for all the answers here and then congrats again on all the progress. And looking forward to the progress going forward.

是的，太棒了。再次感謝您在這裡的所有回答，並再次祝賀您取得的所有進展。並期待未來的進展。

Thank you.

謝謝。

Yi Chen, H.C. Wainwright.

陳懿，H.C.溫賴特。

Hi, thank you for taking my question. Regarding the utility of the DMAb technology, particularly in terms of the Phase 1 proof-of-concept evaluating DMAb targeting COVID-19.

你好，謝謝你回答我的問題。關於 DMAb 技術的實用性，特別是針對 COVID-19 的 DMAb 的第 1 階段概念驗證評估。

Could you tell us how durable is the in vivo antibody production? And in future clinical trials, in case the produced antibody has some undesirable effects, is there a way that you can turn off the antibody production? Thank you.

您能告訴我們體內抗體產生的持久性有多好嗎？還有在未來的臨床試驗中，萬一產生的抗體出現了一些不良反應，有沒有辦法可以關閉抗體的產生？謝謝。

Yeah. Hi, Yi, great question. So in terms of how durable the antibody production is, I mean, as I think you saw on the slide, we presented and if you take a look at the preprint as well, we're now out for 72 weeks and we're not seeing any drop in terms of the levels that we're seeing secreted into the serum. So our production seems to be holding up over 72 weeks. So we think that's really excellent durability.

是的。你好，Yi，這個問題問得好。因此，就抗體產生的持久性而言，我的意思是，正如您在幻燈片上看到的，我們展示了，如果您也看一下預印本，我們現在已經進行了 72 週，我們沒有看到分泌到血清中的水平有任何下降。因此我們的生產似乎可以維持 72 週以上。因此我們認為這確實具有極佳的耐用性。

And in terms of future clinical trials, I mean, we're excited by what this technology could mean across a wide range of targets. There are either inducible or repressible [promosis] that you could use to turn off the genes or turn on the genes to be able to control expression.

就未來的臨床試驗而言，我們對這項技術在廣泛目標範圍內的意義感到非常興奮。您可以使用可誘導或可抑制的 [promosis] 來關閉基因或打開基因以控製表達。

But I think initially we'll be focused on targets that we're already in the right therapeutic range and where there's less concern about potentially turning off those antibodies. So I think those will be the targets that we focus on initially.

但我認為，最初我們將重點放在那些已經處於正確治療範圍內的目標，而不太擔心可能會關閉這些抗體。所以我認為這些都會是我們最初關注的目標。

And in terms of the location of the antibody production, is it primarily produced in certain parts of the body or it's produced throughout the body?

就抗體產生的位置而言，它主要在身體的某些部位產生，還是在整個身體中產生？

Yeah, again, great question. So we're administering our DMAbs into the deltoid muscle in the arm. And the DMAbs are actually produced within the myocytes within the muscle cells. They're produced as heavy and light chain proteins which then are self assembled and then are secreted into the bloodstream from the myocytes. So it's actually production in these muscle cells which are pretty long-lit cells, the [myocytes].

是的，又問了一個好問題。因此我們將 DMAbs 注入手臂的三角肌。DMAb 實際上是在肌肉細胞內的肌肉細胞內產生的。它們以重鏈和輕鏈蛋白質的形式產生，然後自我組裝，然後從肌肉細胞分泌到血液中。所以它實際上是在這些肌肉細胞中產生的，這些肌肉細胞是相當長亮的細胞，[肌肉細胞]。

Okay, got it. Thank you.

好的，明白了。謝謝。

Gregory Renza, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Gregory Renza。

Hi, guys, it's [Anish Shon] for Greg. Congrats on the progress this quarter and thanks for taking our questions. Just a couple from us. As you think about taking 3107 commercial in the future, potentially, what are your going assumptions for labeling and what particular points would you like to see that could play to the strengths of your program, both on its own merits and even over competitors? Thanks so much.

大家好，我是 Greg 的 [Anish Shon]。恭喜本季的進展，並感謝您回答我們的問題。我們中只有一對夫婦。當您考慮未來將 3107 商業化時，您對標籤的假設是什麼？您希望看到哪些特定的點可以發揮您的計劃的優勢，既能發揮其自身的優點，又能超越競爭對手？非常感謝。

Yeah, great question, Anish. I mean, first and foremost, I think we're really confident in the very strong product profile that we're seeing with INO-3107 with -- we've observed great and durable efficacy. The treatment's been very tolerable.

是的，阿尼什，這個問題問得很好。我的意思是，首先，我認為我們對 INO-3107 非常強大的產品特性非常有信心——我們觀察到了其出色且持久的功效。治療效果非常好。

And then it's -- we've designed really 3107 with the patient in mind, so we have a very patient-centric treatment regimen. We don't require any scoping or any surgery during the dosing window. We're able to administer the treatment in the doctor's office, so there's no need for them to go to -- to go for instance, to an infusion center to receive the product.

然後——我們在設計 3107 時確實考慮到了患者，因此我們有一個以患者為中心的治療方案。我們不需要在給藥窗口期間進行任何檢查或手術。我們能夠在醫生辦公室進行治療，所以他們無需前往——例如去輸液中心接受產品。

So we think that product profile is really, really compelling. I think, obviously we're still very close to filing our BLA. And so I think we can't really comment at the moment about the potential label implications, but I think the data that we've generated in this patient population who previously had two or more surgeries it's really compelling. Mike, can you have a few things to add there?

因此我們認為該產品簡介確實非常引人注目。我認為，顯然我們仍然非常接近提交 BLA。因此我認為我們目前無法對潛在的標籤含義發表評論，但我認為我們在先前接受過兩次或兩次以上手術的患者群體中產生的數據確實令人信服。麥克，你能補充幾點嗎？

Yeah, I mean, I -- when you have these discussions with the agency, your label is always a negotiation, but ultimately it is about sharing the risk benefit ratio for the physician and for the patient.

是的，我的意思是，當您與機構進行這些討論時，您的標籤始終是一種談判，但最終是為了分享醫生和患者的風險收益比。

And I think as you heard today, I mean, we're able to now really demonstrate the durable clinical effect of IMO-3107. And I would hope we'll be able to discuss that with the agency and get that taken into account because RRP is not a disease that's defined by a 12-month period. It's a chronic viral infection, and these patients have multiple surgeries. So I think it'll be an interesting discussion that we'll have with the agency in the future.

我想正如您今天所聽到的，我們現在能夠真正證明 IMO-3107 的持久臨床效果。我希望我們能夠與該機構討論這個問題，並將其考慮在內，因為 RRP 不是一種以 12 個月為週期定義的疾病。這是一種慢性病毒感染，這些患者需要接受多次手術。因此我認為我們將來與該機構進行的討論將會很有趣。

Roger Song, Jefferies.

傑富瑞（Jefferies）的羅傑·宋（Roger Song）。

Hey, team, thank you for taking our questions. This is Liang Cheng for Roger. So just two questions from us regarding RRP and the 3107. The first one, really great to see the durability data of the 3107 up to two years, three years.

嘿，團隊，感謝你們回答我們的問題。我是梁成，為羅傑服務。所以我們只想問兩個關於 RRP 和 3107 的問題。第一個，很高興看到 3107 的耐用性數據長達兩年、三年。

So just wondering, how should we think about redosing strategy if you think about the durability and increased response there? And second, as we think about the treatment of RRP disease, so how should we think about, in a longer term, the epidemiology and addressable market there? Thank you.

所以只是想知道，如果考慮耐用性和增強的反應，我們應該如何考慮重新給藥策略？其次，當我們考慮 RRP 疾病的治療時，從長遠來看，我們應該如何考慮疾病的流行病學和潛在市場？謝謝。

Thanks. I caught your first question about the redosing strategy. I'm sorry, I didn't quite catch your second question. Could you repeat that?

謝謝。我聽到了您關於重新給藥策略的第一個問題。抱歉，我沒聽清楚你的第二個問題。你能再說一次嗎？

Yes, so as we have now have the -- those 3107 and those treatment -- new treatment for RRP, so do we expect lower epidemiology, like decreasing epidemiology over time, and how should we think about the addressable market there?

是的，所以現在我們有了 3107 和那些治療方案，針對 RRP 的新療法，那麼我們是否預計流行病學會降低，例如隨著時間的推移流行病學會降低，我們應該如何看待那裡的潛在市場？

Yeah, great question. Okay. Mike, do you want to take the redosing and then I'll take the epi question?

是的，很好的問題。好的。麥克，你想先重新服藥，然後我來回答癲癇的問題嗎？

Yeah, absolutely. So I mean as we said in today's call, we're actually still deciding on the redosing strategy. I think as we looked to our sort of excellent efficacy, it did make us think about how we could design the clinical trial to get a future labeling change.

是的，絕對是如此。所以我的意思是，正如我們在今天的電話會議上所說的那樣，我們實際上仍在決定重新給藥策略。我認為，當我們關注這種優異的療效時，它確實讓我們思考如何設計臨床試驗以獲得未來的標籤變更。

I think we're also sort of in the position now that we started off this process, looking at it very much from a sort of regulatory lens of complete remission, partial remission, et cetera. But really that isn't how the physicians look at this. They look at this at a totality of the surgeries that these patients have.

我認為我們現在也處於這樣的位置，因為我們開始了這個過程，從完全緩解、部分緩解等等的監管角度來看待它。但事實上醫生們卻不這麼認為。他們對這些病人所接受的所有手術進行了整體評估。

And so we want to, as we think about this strategy, see what -- see how we can reduce the surgeries to hopefully zero and how we can maintain that excellent clinical response that we've seen. So I mean hopefully we'll have some more details in upcoming calls.

因此，當我們思考這一策略時，我們希望看到——我們如何能夠將手術減少到零，以及如何保持我們所看到的良好臨床反應。所以我希望我們能在接下來的電話會議中提供更多詳細資訊。

But at the moment, we really are still thinking about how best to accomplish the goals, knowing exactly what our platform is capable of doing with the redosing and being able to boost that CDA response that we've seen with 3100 in the past.

但目前，我們確實仍在思考如何最好地實現目標，確切地了解我們的平台透過重新給藥能夠做什麼，以及能夠增強我們過去在 3100 中看到的 CDA 反應。

Yeah, I think that's a really excellent point. With our DNA medicines, we're able to redose from a previous product, VGX-3100. We've shown that we can boost the existing T cell responses by going in with a single dose later.

是的，我認為這是一個非常好的觀點。利用我們的 DNA 藥物，我們可以重新使用先前的產品 VGX-3100。我們已經證明，透過稍後注射單劑量可以增強現有的 T 細胞反應。

So we're really confident that we can continue to maintain the immune response that's associated with clinical benefits, potentially augment the immune response and so we're very excited by what that means for potential long-term treatment for RRP.And as Mike said, this is a chronic often lifelong disease, so being able to provide durable clinical benefits really incredibly important.

因此，我們非常有信心，我們可以繼續維持與臨床益處相關的免疫反應，有可能增強免疫反應，因此，我們對這對 RRP 的潛在長期治療意味著什麼感到非常興奮。正如麥克所說，這是一種慢性、通常是終身存在的疾病，因此能夠提供持久的臨床益處確實非常重要。

In terms of the epidemiology, what we're seeing is in most developed countries where the vaccination rates are around sort of 50% or 60%, we're still seeing large numbers of RRP cases in adults which don't seem to be affected by the vaccination rates yet. The level of cases in adults seems to be holding pretty steady.

從流行病學角度來看，我們看到，在大多數已開發國家，疫苗接種率約為 50% 或 60%，但我們仍然看到大量成年人出現 RRP 病例，而這似乎尚未受到疫苗接種率的影響。成人病例水準似乎保持相當穩定。

And if you think about the epidemiology of RRP, you see a peak of disease cases around age 5 to 7, another peak in the age of 30 group, and then another peak in the late 50s early 60s. And currently in the US, for instance, vaccination for HPV is only around 50% in males, below 60% in females, so a large proportion of the adult population, I think, it's been estimated that around 70%, is not protected against HPV-6 and 11.

如果您了解 RRP 的流行病學，您會發現在 5 至 7 歲左右會出現一個發病高峰，在 30 歲年齡段會出現另一個高峰，然後在 50 年代末 60 年代初會出現另一個高峰。例如，目前在美國，男性的 HPV 疫苗接種率僅為 50% 左右，女性的接種率低於 60%，所以我認為，很大一部分成年人口（據估計約有 70%）沒有受到 HPV-6 和 11 的保護。

And it's also not entirely clear how long the vaccine (technical difficulty) the protective effects remain as well. So unfortunately, I think it looks as though RRP is going to be with us for several generations to come.

而且還不完全清楚疫苗（技術難度）的保護效果能持續多久。因此不幸的是，我認為 RRP 似乎還會伴隨我們幾個世代。

Where we are seeing a decrease in the number of patients and the impact of vaccination is in pediatric RRP, where the number of pediatric cases are declining. But we're not seeing any impact on cases in the adult population. And in fact, we think this is actually an underdiagnosed disease in the adult population.

我們看到患者數量在減少，疫苗接種的影響體現在兒科 RRP 方面，其中兒科病例數正在下降。但我們沒有看到對成年人口病例有任何影響。事實上，我們認為這實際上是成年人群中一種未被充分診斷​​的疾病。

Got it. Very helpful. Thank you, Jackie and Mike.

知道了。非常有幫助。謝謝你，Jackie 和 Mike。

Thank you. And there are no further questions at this time. I will now hand the call back to Ms. Jacqueline Shea for any closing remarks.

謝謝。目前沒有其他問題。現在我將把電話交還給 Jacqueline Shea 女士，請她做最後發言。

Thank you. As we've outlined here today, we are moving into 2025 with very focused strategic priorities. First and foremost is completing the next steps necessary for submitting our BLA for 3107. At the same time, we'll be continuing to advance our commercial readiness plan so we can hit the ground running and use our compelling product profile to its full advantage.

謝謝。正如我們今天在這裡概述的那樣，我們將帶著非常集中的策略重點邁入 2025 年。首要的是完成提交 3107 的 BLA 所需的後續步驟。同時，我們將繼續推進我們的商業準備計劃，以便我們能夠立即開始行動並充分利用我們引人注目的產品優勢。

And finally, we'll continue driving progress across our pipeline, advancing promising programs like 3112 and leveraging potential partnership opportunities. This includes building on the breakthrough potential of our DMAb program and other next gen DNA medicine technologies.

最後，我們將繼續推動整個管道的進展，推進 3112 等有前景的項目，並利用潛在的合作機會。這包括利用我們的 DMAb 計劃和其他下一代 DNA 醫學技術的突破性潛力。

I'll close today by noting that the inspiration for all of this work continues to be the patients around the world who could benefit from the power and potential of DNA medicine. For those suffering from RRP in particular, we're strongly motivated by the understanding that every day and every surgery matters. Thank you for your attention and good evening, everyone.

今天最後，我想說，所有這些工作的靈感仍然來自於全世界能夠從 DNA 醫學的力量和潛力中受益的患者。特別是對於那些患有 RRP 的患者，我們強烈地認識到每一天、每一次手術都很重要。謝謝大家的關注，大家晚上好。

Thank you. And that concludes our conference for today. Thank you all for participating, you may now disconnect.

謝謝。今天的會議到此結束。感謝大家的參與，現在可以斷開連線了。