Inovio Pharmaceuticals Inc (INO) 2024 Q3 法說會逐字稿

Good afternoon, ladies and gentlemen and welcome to the Inovio third-quarter 2024 financial results conference call at this time. (Operator Instructions) This call is being recorded on Thursday, November 14, 2024.

女士們先生們下午好，歡迎此時參加 Inovio 2024 年第三季財務業績電話會議。（操作員說明）此電話錄音時間為 2024 年 11 月 14 日星期四。

I would now like to turn the conference over to Thomas Hong, Manager of Investor Relations. Please go ahead.

我現在想將會議交給投資者關係經理 Thomas Hong。請繼續。

Good afternoon and thank you for joining the Inovio third quarter, 2024 financial results conference call. Joining me on today's call are Dr. Jackie Shea, President and Chief Executive Officer; Dr. Mike Sumner, Chief Medical Officer; Peter Kies, Chief Financial Officer; Steve Egge, Chief Commercial Officer; and Dr. Matthew Morrow, VP of Translational Sciences.

下午好，感謝您參加 Inovio 2024 年第三季財務業績電話會議。與我一起參加今天電話會議的還有總裁兼執行長 Jackie Shea 博士；麥克‧薩姆納博士，首席醫療官；彼得‧凱斯，財務長； Steve Egge，商務長；和轉化科學副總裁 Matthew Morrow 博士。

Today's call will review our corporate and financial information for the quarter ended September 30, 2024, as well as provide a general business update. Following prepared remarks, we will conduct a question-and-answer segments. During the call, we will be making forward-looking statements regarding future events and the future performance of the company.

今天的電話會議將審查我們截至 2024 年 9 月 30 日的季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。在電話會議期間，我們將就未來事件和公司未來業績做出前瞻性陳述。

These events relate to our business plans to develop Inovio's DNA medicines platform, which include clinical and regulatory developments and timing of clinical data readouts and planned regulatory submissions, along with capital resources and strategic matters. All of these statements are based on the beliefs and expectations of management as of today.

這些事件與我們開發 Inovio DNA 藥物平台的業務計劃有關，其中包括臨床和監管發展、臨床數據讀出的時間表和計劃的監管提交，以及資本資源和戰略事項。所有這些陳述均基於截至目前管理層的信念和期望。

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. 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.

實際事件或結果可能有重大差異。我們建議您參閱我們不時向 SEC 提交的文件，這些文件在「風險因素」標題下確定了可能導致實際結果與公司口頭表達的結果以及本聲明中的聲明存在重大差異的重要因素。 。本次電話會議正在進行網絡直播，您可以在我們的網站 ir.inovio.com 上找到鏈接，並且將在本次電話會議結束後不久進行重播。

I will now turn the call over to Inovio's President and CEO, Dr. Jacqui Shea.

我現在將把電話轉給 Inovio 的總裁兼執行長 Jacqui Shea 博士。

Good afternoon and thank you to everyone for joining today's call. This quarter, we continued to make progress on the key objectives we've been focused on for 2024 to deliver value to stakeholders in the near, mid and longer term and most importantly, deliver on the promise of DNA medicine for patients. Those objectives include, firstly, advancing our lead product candidate, INO-3107 towards commercialization; secondly, advancing our pipeline; and thirdly, continuing to strengthen our business overall.

下午好，感謝大家參加今天的電話會議。本季度，我們繼續在 2024 年重點關注的關鍵目標上取得進展，在近期、中期和長期為利益相關者提供價值，最重要的是，兌現 DNA 醫學對患者的承諾。這些目標包括，首先，推動我們的主要候選產品 INO-3107 走向商業化；其次，推進我們的管道；第三，繼續加強我們的整體業務。

Today, I will provide an overview of our progress and then ask my colleagues to provide greater detail. To begin with, we've recently announced important additional immunology data supporting the proposed mechanism of action for 3107 and its potential to eliminate or reduce the number of surgeries RRP patients have to face. This extensive immunological characterization data, highlighting the ability of 3107 to induce T-cell responses that correspond to the clinical benefit observed in our Phase 1/2 trial has been presented at two scientific conferences, including the International Papillomavirus Conference this week.

今天，我將概述我們的進展，然後請我的同事提供更多細節。首先，我們最近宣布了重要的額外免疫學數據，支持 3107 的建議作用機制及其消除或減少 RRP 患者必須面臨的手術數量的潛力。這些廣泛的免疫學特徵數據強調了3107 誘導T 細胞反應的能力，這與我們在1/2 期試驗中觀察到的臨床益處相對應，已在包括本週的國際乳頭瘤病毒會議在內的兩個科學會議上發表。

We have also presented the full safety and efficacy data demonstrating that 3107 was shown to be well tolerated and have clinical benefit in our Phase 1/2 trial at two recent scientific conferences. We believe the powerful combination of this additional data further highlight the potential for 3107 to become the preferred choice for the broadest number of RRP patients should it be approved. Mike and Steve will provide further details on this later in today's call.

我們還提供了完整的安全性和有效性數據，證明 3107 在最近兩次科學會議上的 1/2 期試驗中顯示出良好的耐受性並具有臨床益處。我們相信，這些額外數據的強大組合進一步凸顯了 3107 如果獲得批准，有可能成為最廣泛的 RRP 患者的首選。麥克和史蒂夫將在今天的電話會議中提供有關此事的更多詳細資訊。

Moving on to regulatory matters. In August, we held a positive pre-BLA meeting with the FDA. Since then, we have continued preparing for submission of our BLA targeted in mid-2025. We expect to have all non-device-related modules for the BLA completed by the end of this year. You'll recall during our last quarterly call, we announced we have recently identified a manufacturing issue for the single-use component of our device during the testing required for our BLA submission.

繼續討論監管問題。8 月，我們與 FDA 舉行了一次積極的 BLA 前會議。此後，我們繼續準備在 2025 年中期提交 BLA。我們預計 BLA 的所有非設備相關模組將在今年年底前完成。您還記得在我們上一季的電話會議中，我們宣布最近在提交 BLA 所需的測試期間發現了我們設備的一次性組件的製造問題。

We believe we have identified the appropriate resolution for this issue and are making good progress in implementation. In summary, we remain confident in our ability to deliver 3107 to the market for patients as an important and new therapeutic option to treat this devastating disease. As this is our primary focus, we are directing the majority of our resources, both people and financial towards completion of development, BLA submission and preparing for our potential commercialization of 3107.

我們相信我們已經找到了該問題的適當解決方案，並且在實施方面取得了良好進展。總之，我們仍然相信我們有能力將 3107 推向市場，作為治療這種毀滅性疾病的重要的新治療選擇。由於這是我們的首要關注點，我們正在將大部分資源（包括人力和財務）用於完成開發、提交 BLA 並為 3107 的潛在商業化做好準備。

However, even with 3107 as our primary focus, we are mindful of the significant potential of the rest of our pipeline and have continued to make important progress on several other candidates as well. For INO-3112, we've consulted with European regulators regarding the design of our proposed Phase 3 trial evaluating 3112 in combination with the PD-1 inhibitor LOQTORZI as a potential treatment for locally advanced HPV-16 and HPV-18 positive high-risk oropharyngeal squamous cell carcinoma, also known as throat cancer.

然而，即使 3107 是我們的主要關注點，我們也注意到其餘產品線的巨大潛力，並繼續在其他幾個候選藥物上取得重要進展。對於INO-3112，我們已就我們擬議的3 期試驗的設計諮詢了歐洲監管機構，該試驗評估3112 與PD-1 抑製劑LOQTORZI 聯合作為局部晚期HPV-16 和HPV-18 陽性高風險患者的潛在治療方法口咽鱗狀細胞癌，又稱咽喉癌。

We anticipate conducting this trial in North America and Europe. Previous discussions with the FDA have indicated alignment with the proposed trial design. Continuing in oncology for INO-5401, patients continue to be dosed in the GBM-001 trial in newly diagnosed glioblastoma that combines 5401 with Regeneron's PD-1 checkpoint inhibitor, Libtayo. Regeneron and Inovio have discussed that an appropriate next step for GBM could be a controlled Phase 2 trial.

我們預計在北美和歐洲進行這項試驗。先前與 FDA 的討論表明與擬議的試驗設計保持一致。繼續進行 INO-5401 的腫瘤學治療，患者繼續在新診斷的膠質母細胞瘤 GBM-001 試驗中接受給藥，該試驗將 5401 與 Regeneron 的 PD-1 檢查點抑制劑 Libtayo 結合。Regeneron 和 Inovio 討論了 GBM 的下一步合適的步驟可能是進行受控的 2 期試驗。

A separate trial evaluating 5401 in patients with the BRCA mutation is ongoing at the Basser Center at the University of Pennsylvania. We also have an upcoming meeting scheduled with the FDA later this quarter to discuss the Phase 2 trial design and development pathway for INO-4201 as a heterologous boost to the FDA-licensed Ebola vaccine, Ervebo.

賓州大學巴塞爾中心正在進行一項針對 BRCA 突變患者進行 5401 評估的單獨試驗。我們還計劃在本季度稍後與 FDA 舉行一次會議，討論 INO-4201 的 2 期試驗設計和開發途徑，作為 FDA 許可的伊波拉疫苗 Ervebo 的異源增強劑。

From our earlier-stage candidates, we expect clinical data from an ongoing Phase 1, study with DNA-encoded monoclonal antibodies to be submitted to a peer-reviewed publication by year-end. We believe this will be the first clinical data for DNA-delivered monoclonal antibodies to be reported and illustrates what we believe to be the transformational potential of our DNA medicines platform.

我們預計正在進行的第一階段 DNA 編碼單株抗體研究的臨床數據將在年底前提交給同行評審的出版物。我們相信這將是第一個報告的 DNA 遞送單株抗體的臨床數據，並說明了我們認為我們的 DNA 藥物平台的變革潛力。

Finally, our commitment to financial discipline and strengthening our business is a core component of our strategy for success. While we've made substantial progress on our overall goals, we've done so while continuing to reduce our operating expenses. We closed the third quarter with $84.4 million in cash, cash equivalents and short-term investments and with no debt.

最後，我們對財務紀律和加強業務的承諾是我們成功策略的核心組成部分。雖然我們在總體目標上取得了實質進展，但我們在這樣做的同時繼續減少了營運費用。截至第三季末，我們擁有 8,440 萬美元的現金、現金等價物和短期投資，沒有債務。

Now I'll turn it over to Mike for some additional insights from the new data on 3107. Mike?

現在我將把它交給 Mike，讓他從 3107 的新數據中獲得一些額外的見解。麥克風？

Thanks, Jacqui. Before I dive into the new data that we have presented at several scientific conferences over the last couple of weeks, I think it's important to review why we are working so hard to bring INO-3107 to patients. RRP is a rare HPV-related disease characterized by small wart-like growth called papillomas, found in the respiratory tract. People with RRP mount an insufficient immune response that's unable to prevent or clear the HP infection from their airways, so the papillomas can grow unchecked.

謝謝，雅基。在深入研究過去幾週我們在幾次科學會議上展示的新數據之前，我認為有必要回顧一下我們為何如此努力地將 INO-3107 帶給患者。RRP 是一種罕見的 HPV 相關疾病，其特徵是呼吸道中發現的稱為乳頭狀瘤的小疣狀生長。患有 RRP 的人免疫反應不足，無法預防或清除呼吸道中的 HP 感染，因此乳頭狀瘤可能會不受控制地生長。

The papillomas often cause difficulty speaking or complete voice loss, difficulty swallowing, shortness of breath or choking episodes. The current standard of care is surgery to clear out the papillomas, but that doesn't address the underlying viral cause of the disease and the papillomas grow back, setting patients up for an endless cycle of resurgence of symptoms and need for more surgery. Every single surgery presents a risk of permanent vocal cord damage, reinforcing what patients have said time and again that a reduction of even one surgery would be life-changing.

乳頭狀瘤常導致說話困難或完全失聲、吞嚥困難、呼吸急促或窒息發作。目前的護理標準是手術清除乳頭瘤，但這並不能解決疾病的潛在病毒原因，而且乳頭狀瘤會重新生長，使患者陷入症狀復發的無休止循環，並需要更多手術。每一次手術都會帶來永久性聲帶損傷的風險，這印證了患者一再說過的觀點：即使減少一次手術也會改變生活。

That patient experience has been central to our efforts to develop 3107, which we believe has the potential to change the treatment paradigm for RRP. Designed to generate antigen-specific cytotoxic CD8 T-cells targeting both HPV-6 and HPV-11, 3107 is a potential novel non-surgical treatment option for RRP patients. In our Phase 1/2 clinical trial, we observed a compelling combination of clinical benefit and tolerability across the disease spectrum of severity and including both HPV-6 and 11 driven disease.

患者體驗對於我們開發 3107 的努力至關重要，我們相信 3107 有可能改變 RRP 的治療模式。3107 旨在產生針對 HPV-6 和 HPV-11 的抗原特異性細胞毒性 CD8 T 細胞，是 RRP 患者潛在的新型非手術治療選擇。在我們的 1/2 期臨床試驗中，我們觀察到在整個疾病嚴重程度範圍內（包括 HPV-6 和 11 驅動的疾病），臨床益處和耐受性令人信服地結合在一起。

In addition, we saw the generation of a significant and targeted immune response that was associated with a reduction or elimination of surgeries for these patients. We believe that the growing body of evidence shows that 3107 could be used to treat the vast majority of RRP patients and supports its potential to be the preferred product of choice by patients, healthcare providers and payers, if approved.

此外，我們還看到了顯著且有針對性的免疫反應的產生，這與減少或消除這些患者的手術有關。我們相信，越來越多的證據表明，3107 可用於治療絕大多數 RRP 患者，並支持其在獲得批准後成為患者、醫療保健提供者和付款人的首選產品的潛力。

At the International Society of Vaccines Conference and the Fall Voice Conference this past October, Inovio presented its full safety and efficacy data for the Phase 1/2 trial, which is summarized here. In the trial, the overall clinical response defined as patients experiencing a decrease in the number of surgical interventions in the year after the initial 3107 administration compared to the prior year was 81% or [26] of the 32 enrolled patients.

在去年 10 月的國際疫苗學會會議和 Fall Voice 會議上，Inovio 展示了 1/2 期試驗的完整安全性和有效性數據，總結如下。在該試驗中，32 名入組患者的整體臨床緩解率（定義為首次 3107 給藥後一年內與前一年相比手術幹預次數減少的患者）為 81% 或 [26]。

This number includes 28% that required no surgical intervention during or after the dosing window. These are our complete responders. Further, 44% of patients had a partial response, defined as a reduction of at least 50% in the number of surgeries when compared to the prior year. The overall response rate calculated by adding our complete responders and partial responders was 72% or '23 out of 32 patients. Importantly, in our trial design, we counted every surgery after day zero because every surgery matters to patients.

這個數字包括 28% 在給藥窗口期間或之後不需要手術幹預的患者。這些是我們的完整響應者。此外，44% 的患者出現部分緩解，即與前一年相比，手術數量減少至少 50%。透過將完全緩解者和部分緩解者相加計算得出的整體緩解率為 72%，即 32 名患者中的 23 名。重要的是，在我們的試驗設計中，我們在零天後計算了每次手術，因為每次手術對患者都很重要。

On this slide, you can see our overall safety data. 3107 was well-tolerated in the study, with the most common treatment-related adverse events being injection site pain reported in less than a third of patients, supporting that our CELLECTRA electroporation device was well-tolerated by patients and was also easy to use by healthcare providers. Fatigue was the next most frequent reported treatment-related AE in just three patients.

在此投影片上，您可以看到我們的整體安全資料。 3107 在研究中具有良好的耐受性，最常見的治療相關不良事件是不到三分之一的患者報告的注射部位疼痛，這證明我們的CELLECTRA 電穿孔裝置具有良好的患者耐受性，並且也易於患者使用醫療保健提供者。僅在三名患者中，疲勞是第二常見的治療相關 AE。

No treatment-related adverse events greater than Grade 2 severity were reported. One of the core strengths of our DNA medicine platform is the ability to drive a T-cell response, which is particularly important for treating chronic viral disease. You can see on this slide the proposed mechanism of action for 3107, inducing HPV antigen-specific T-cell responses in the blood, then having those T-cells travel to and infiltrate the papilloma and airway tissue and ultimately eradicate the HPV-infected cells to reduce or eliminate the need for surgery.

沒有報告嚴重程度超過 2 級的治療相關不良事件。我們 DNA 醫學平台的核心優勢之一是能夠驅動 T 細胞反應，這對於治療慢性病毒性疾病尤其重要。您可以在這張投影片上看到 3107 的建議作用機制，誘導血液中 HPV 抗原特異性 T 細胞反應，然後讓這些 T 細胞前往並滲透乳頭狀瘤和氣道組織，最終根除 HPV 感染的細胞以減少或消除手術的需要。

I'd like to now turn to our new immunology data that we have shared at the recent scientific conferences, including this week at the International Papilloma Virus Conference. To further characterize immune responses to 3107, we analyzed blood and tissue samples from patients in our Phase 1/2 trial. Our goal was to evaluate the individual steps that combine into the proposed mechanism of action that I just presented.

我現在想談談我們在最近的科學會議上分享的新免疫學數據，包括本週在國際乳突病毒會議上分享的數據。為了進一步表徵對 3107 的免疫反應，我們分析了 1/2 期試驗中患者的血液和組織樣本。我們的目標是評估結合到我剛才提出的行動機制中的各個步驟。

We conducted a number of very extensive immunological assessments on blood and tissue samples to one, confirm the induction, activation and expansion of cytotoxic T-cells with antigen specificity to HPV-6 and 11; and two, to assess the level and form of immunological change from baseline, including T-cell infiltration and profiling and the potential impact of the papilloma micro-environment on clinical effect.

我們對血液和組織樣本進行了許多非常廣泛的免疫學評估，其一，確認對 HPV-6 和 11 具有抗原特異性的細胞毒性 T 細胞的誘導、活化和擴增；第二，評估相對於基線的免疫學變化的水平和形式，包括T細胞浸潤和分析以及乳頭狀瘤微環境對臨床效果的潛在影響。

In short, what we discovered was very compelling. The data demonstrated the ability of 3107 to do exactly what it was designed to do, induce HPV antigen-specific T-cell responses in the blood that infiltrate papilloma and airway tissues and that they are the right kind of T-cells to eradicate HPV-infected cells and ultimately reduce or eliminate the need for surgery. Overall, the key takeaways from this study include 5 main points.

簡而言之，我們的發現非常引人注目。數據證明 3107 能夠完全發揮其設計作用，誘導血液中 HPV 抗原特異性 T 細胞反應，浸潤乳頭狀瘤和氣道組織，並且它們是根除 HPV 的正確 T 細胞類型。 。整體而言，本研究的主要結論包括 5 個要點。

First, INO-3107 generates the right kind of immune responses to fight HPV for the vast majority of RRP patients. In our research, we see generation of HPV-6 and HPV-11 antigen-specific cytotoxic T-cells with responses that are durable out to 52 weeks, indicating a long-lived memory response, which is important for the treatment of a chronic viral disease like RRP. Second, the newly generated T-cells get to where they need to go.

首先，INO-3107 為絕大多數 RRP 患者產生正確的免疫反應來對抗 HPV。在我們的研究中，我們看到 HPV-6 和 HPV-11 抗原特異性細胞毒性 T 細胞的產生，其反應可持續長達 52 週，表明存在長效記憶反應，這對於治療慢性病毒性疾病非常重要像RRP這樣的​​疾病。其次，新生成的 T 細胞到達它們需要去的地方。

Our data shows that T-cells travel from the blood to the papilloma and airway tissue and the resulting inflammatory and antiviral responses are seen in the tissue. Third, the immune response we have observed is targeted and specific to treatment with INO-3107. We saw expansion of both pre-existing T-cell clones and the emergence of new T-cells in the blood. These new T-cells could not be detected prior to treatment, meaning the majority of T-cells seen in airway tissue at the 52-week time point were emergent clones.

我們的數據顯示，T 細胞從血液移動到乳頭狀瘤和氣道組織，並在組織中觀察到由此產生的發炎和抗病毒反應。第三，我們觀察到的免疫反應是針對 INO-3107 治療的針對性和特異性的。我們看到血液中原有 T 細胞克隆的擴增和新 T 細胞的出現。這些新的 T 細胞在治療前無法被檢測到，這意味著 52 週時間點氣道組織中看到的大多數 T 細胞都是新出現的克隆。

The presence of these new T-cells in the tissue corresponds with the clinical benefit we saw in the trial. Fourth, we were also able to show that immune responses in responders are different to those seen in non-responders. While all 32 patients in the trial were seen to generate an immune response in the blood, the kinetics and magnitude of that response differed based on the clinical response seen. We believe we can build on these initial responses in non-responders through the administration of additional doses.

組織中這些新 T 細胞的存在與我們在試驗中看到的臨床益處相對應。第四，我們也能夠證明，應答者的免疫反應與無應答者的免疫反應不同。雖然試驗中的所有 32 名患者都在血液中產生了免疫反應，但該反應的動力學和程度根據所觀察到的臨床反應而有所不同。我們相信，我們可以透過給予額外劑量來在無反應者中建立這些初步反應。

And finally, from our evaluations to-date, we have looked at elements of the papilloma microenvironment that have been reported in recent scientific literature to impact the potential efficacy of treatment. To-date, we have not found evidence that these elements appear to restrict the clinical benefit of 3107. This immunology data is currently under review at a peer-reviewed journal, and we look forward to providing an update on that publication when available.

最後，根據我們迄今為止的評估，我們研究了最近科學文獻中報告的影響治療潛在療效的乳頭狀瘤微環境要素。迄今為止，我們尚未發現證據表明這些因素似乎限制了 3107 的臨床益處。該免疫學數據目前正在同行評審期刊上進行評審，我們期待在可用時提供該出版物的更新。

So in summary, I would like to point out why this new data is so important to the potential of INO-3107. First and foremost, we believe the immunology data support the biological mechanism of action of 3107. This data will be an important component of our upcoming BLA submission and other future regulatory filings. The data confirmed that 3107 effectively targets HPV-6 and HPV-11, the strains that cause the vast majority of RRP disease.

總而言之，我想指出為什麼這個新數據對 INO-3107 的潛力如此重要。首先，我們相信免疫學數據支持 3107 的生物學作用機制。這些數據將成為我們即將提交的 BLA 和其他未來監管文件的重要組成部分。數據證實，3107 能有效靶向 HPV-6 和 HPV-11，這兩種病毒是導致絕大多數 RRP 疾病的病毒株。

The data confirmed that 3107 generates new and expands existing populations of T-cells and activates them to eliminate the underlying cause of the disease. The data also support that 3107 can have clinical benefit across the disease severity spectrum and in both HPV-6 and HPV-11 driven disease. Remember that patients tell us that every surgery matters. So our goal is to be able to treat patients with RRP regardless of the severity of disease.

數據證實，3107 可以產生新的 T 細胞並擴大現有的 T 細胞群，並激活它們以消除疾病的根本原因。數據還支持 3107 可以在整個疾病嚴重程度範圍以及 HPV-6 和 HPV-11 驅動的疾病中具有臨床益處。請記住，患者告訴我們每次手術都很重要。因此，我們的目標是能夠治療 RRP 患者，無論疾病的嚴重程度如何。

In short, we believe these data provide compelling evidence that INO-3107, if approved, can be a game changer for RRP patients by reducing their need for repeat surgeries to treat their disease. I'd also like to mention that in addition to this important immunology work, we have also recently completed a retrospective study investigating the long-term durability of clinical response seen in patients treated in our Phase 1/2 study. We anticipate announcing that data by year-end.

簡而言之，我們相信這些數據提供了令人信服的證據，證明 INO-3107 如果獲得批准，可以透過減少 RRP 患者重複手術治療疾病的需要來改變遊戲規則。我還想提一下，除了這項重要的免疫學工作外，我們最近還完成了一項回顧性研究，調查在 1/2 期研究中治療的患者中觀察到的臨床反應的長期持久性。我們預計在年底前公佈該數據。

On that note, I'll now turn it over to our Chief Commercial Officer, Steve Egge, for an update on our commercial efforts. Steve?

就此而言，我現在將其轉交給我們的首席商務官 Steve Egge，以了解我們商業工作的最新情況。史蒂夫？

Thanks, Mike. Hello, everyone. At our last quarterly report, I outline the significant opportunity I see for 3107 based on its compelling product profile.

謝謝，麥克。大家好。在我們的上一季報告中，我根據 3107 引人注目的產品概況概述了我所看到的重大機會。

Over the last quarter, I've worked closely with our internal team and external consultants to continue to develop and refine our plans for the launch of 3107. If we receive FDA approval, we're making important progress and focused on developing a go to market strategy that's rooted in ensuring we meet physician payer and most importantly, patient needs.

在上個季度，我與我們的內部團隊和外部顧問密切合作，繼續制定和完善 3107 的推出計劃。如果我們獲得 FDA 的批准，我們將取得重要進展，並專注於制定進入市場策略，該策略植根於確保我們滿足醫生付款人以及最重要的是患者的需求。

We've conducted a significant amount of market research to develop key insights with stakeholders, to ensure we have a deep understanding of the market and the opportunity for 3107 we have repeatedly heard from patients that every single surgery matters and that a reduction in even one surgery makes a meaningful difference in the lives of patients.

我們進行了大量的市場研究，與利益相關者一起形成關鍵見解，以確保我們對市場和3107 的機會有深入的了解，我們多次從患者那裡聽到，每一次手術都很重要，甚至減少一次手術手術對患者的生活產生了有意義的改變。

Because of the potential of a competitive marketplace. I won't go into significant detail. But at a high level, we are making strategic choices in a number of key areas including pricing and access from a pricing standpoint. We do expect to price in line with current rare disease pricing and we've confirmed acceptability of this and feedback from payers that represent the majority of commercial lives in the US. We're also making strategic choices on distribution, physician and patient targeting and segmentation as well as product positioning to ensure we're well differentiated.

因為競爭市場的潛力。我不會詳細討論重要細節。但在較高層面上，我們正​​在許多關鍵領域做出策略選擇，包括從定價角度進行定價和存取。我們確實希望定價與當前的罕見疾病定價一致，並且我們已經確認了這一點的可接受性以及代表美國大多數商業生活的付款人的反饋。我們也在分銷、醫生和患者定位和細分以及產品定位方面做出策略性選擇，以確保我們具有良好的差異化優勢。

We've refined our plan for pathways for product adoption to ensure we provide an optimal customer experience. We did hear from the FDA earlier this month that our proposed brand name for 3107 is acceptable at this time. Of course, the decision of the brand name will be confirmed by the FDA during the process. We're refining our forecasting and gross to net assumptions. And we've also developed strategic imperatives for the business to ensure we're focused on what matters most in a successful product launch.

我們完善了產品採用途徑計劃，以確保提供最佳的客戶體驗。本月早些時候，我們確實從 FDA 獲悉，我們提議的 3107 品牌名稱目前是可以接受的。當然，品牌名稱的決定將在此過程中得到FDA的確認。我們正在完善我們的預測和總淨值假設。我們也制定了業務策略要求，以確保我們專注於成功推出產品中最重要的事情。

And these include metrics on how we'll measure our progress. And finally, we've also planned out planned the buildout of the commercial organization including field teams in 2025. We're planning for a lean and efficient commercial footprint. And as we've communicated previously, we plan to be launch ready by the end of 2025.

其中包括我們如何衡量進展的指標。最後，我們也規劃了 2025 年商業組織（包括現場團隊）的建設。我們正在規劃精實且有效率的商業足跡。正如我們之前所傳達的，我們計劃在 2025 年底前做好發布準備。

I also want to echo Jackie and Mike the new data we've shared today supporting our proposed mechanism of action. Builds on 3107 s compelling product profile and strengthens my belief that 3,107 can treat a broad range of RRP patients and that it could be the preferred choice for RRP patients and physicians. I'll now turn it over to our Chief Financial Officer, Peter Kies for a financial update.

我還想呼應傑基和麥克我們今天分享的支持我們提議的行動機制的新數據。建立在 3107 引人注目的產品簡介的基礎上，增強了我的信念，即 3,107 可以治療廣泛的 RRP 患者，並且它可能是 RRP 患者和醫生的首選。現在我將把它交給我們的財務長 Peter Kies，以獲取最新的財務資訊。

Thanks Steve. Today, I'd like to provide an overview of Inovio's financial results for the third quarter of 2024. As Jackie noted at the start of the call, we are primarily focused on advancing INO-3107. And our goal to submit BLA mid-2025 to support these efforts. We have continued to control our operating expenses for the third quarter ended September 30, 2024. Our total operating expenses dropped 24% from $35.9 million in the third quarter of 2023 to $27.3 million in the third quarter of 2024. A Inovio's net loss for the third quarter of 2024 was $25.2 million or $0.89 per share. Basic and dilutive compared to a net loss of $33.9 million or $1. 52 per share, basic and dilutive for the third quarter of 2023.

謝謝史蒂夫。今天，我想概述一下 Inovio 2024 年第三季的財務表現。正如 Jackie 在電話會議開始時指出的那樣，我們主要專注於推進 INO-3107。我們的目標是在 2025 年中期提交 BLA 以支持這些努力。截至2024年9月30日的第三季度，我們繼續控制營運費用。我們的總營運支出從 2023 年第三季的 3,590 萬美元下降到 2024 年第三季的 2,730 萬美元，下降了 24%。Inovio 2024 年第三季的淨虧損為 2,520 萬美元，即每股虧損 0.89 美元。基本虧損和攤薄虧損相比，淨虧損為 3,390 萬美元或 1 美元。 2023 年第三季基本每股盈餘和稀釋每股盈餘 52 美元。

We finished the third quarter of 2024 with $84.8 million in cash, cash equivalents and short-term investments compared to $145.3 million. As of December 31, 2023, we estimate our cash runway to take us into third quarter 2025. This projection includes an operational net cash burn estimate of approximately $24 million for the fourth quarter of 2024. These cash runway projections do not include any further capital raising activities that Inovio may undertake.

截至 2024 年第三季度，我們的現金、現金等價物和短期投資為 8,480 萬美元，而同期為 1.453 億美元。截至 2023 年 12 月 31 日，我們預計我們的現金跑道將進入 2025 年第三季。該預測包括 2024 年第四季營運淨現金消耗估計約為 2,400 萬美元。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 reminder, you can find our full financial statements in this afternoon's press release as well as in our form, 10-Q filed with the SEC and with that, I'll turn it back over to Jackie.

提醒一下，您可以在今天下午的新聞稿以及我們向 SEC 提交的 10-Q 表格中找到我們的完整財務報表，我會將其轉回給 Jackie。

(Operator Instructions)

（操作員說明）

Jay Olson, Oppenheimer.

傑·奧爾森，奧本海默。

Congrats on all the progress with your 3107 BLA filing in the US. Can you talk about any regulatory updates for 3107 outside the US? It sounds like you're making progress in EU and the UK. What are the timelines for filing in those markets and any update on Japan, China or other major markets? And then I had a follow up if I could.

恭喜您在美國的 3107 BLA 申請取得所有進展。您能談談美國以外地區 3107 的監管更新嗎？聽起來您在歐盟和英國正在取得進展。這些市場的申請時間表是什麼？然後如果可以的話我會進行跟進。

Hi. Jay, nice to hear from you, Mike do you want to comment on where we are with our other regulatory filings?

你好。傑伊，很高興收到你的來信，麥克，你想對我們其他監管文件的進展發表評論嗎？

Yeah, certainly. So I mean, we have met with the UK, and they gave very similar advice to their European colleagues. And that was basically that to gain approval in the European Union and the UK, you're going to need placebo-controlled data that needs to be compelling. And so the rationale behind us running a placebo-controlled study was not only that we would get an indication of just two surgeries, but also that, that data could be used in those markets. But we are going to have to complete that study prior to submitting in Europe. We have not yet reached out to Japan and China. But clearly, they do have RRP. We've spoken to KOLs in some of those regions. And so they are areas of interest for us to progress.

是的，當然。所以我的意思是，我們已經與英國會面，他們向歐洲同事提出了非常相似的建議。基本上，為了獲得歐盟和英國的批准，你將需要安慰劑對照的數據，這些數據需要令人信服。因此，我們進行安慰劑對照研究的理由不僅是我們只能得到兩次手術的指示，而且這些數據可以在這些市場中使用。但我們必須在向歐洲提交之前完成該研究。我們還沒有聯繫日本和中國。但顯然，他們確實有建議零售價。我們已經與其中一些地區的 KOL 進行了交談。因此，它們是我們值得進步的領域。

Okay, great. Thank you very much, super helpful. And then congrats also on the new immunology data that you presented at AACR and IPVC. Could you share any physician feedback that you may have received on that data? And what are physicians ultimately looking for?

好的，太好了。非常感謝，超有幫助。然後也恭喜您在 AACR 和 IPVC 上展示的新免疫學數據。您能否分享您可能收到的有關該數據的任何醫生回饋？醫生最終在尋找的是什麼？

Mike? Do you want to comment here?

麥克風？你想在這裡發表評論嗎？

Yeah. Certainly. I mean, firstly, look, I think as we -- I talked to it, it really is compelling data. Matthew Morrow, who's also on this call, is our translational sciences. Personally, he's done a great job of really characterizing the mechanism of action of 3107.

是的。當然。我的意思是，首先，看，我認為當我們與它交談時，這確實是令人信服的數據。馬修·莫羅（Matthew Morrow）也參加了這次電話會議，他是我們的轉化科學專家。就個人而言，他在真正描述 3107 的作用機制方面做得非常出色。

And I think as we've talked to clinicians and scientists about that data, they really can -- they can see what 3107 is doing from an immunological basis. And I think that just gives them more confidence in the clinical data that we have presented. So I think it just ties in very nicely and also will tie in very nicely as we submit our BLA to link up the clinical data with what's actually happening from an immunological standpoint.

我認為，當我們與臨床醫生和科學家討論這些數據時，他們確實可以——他們可以從免疫學基礎上了解 3107 的作用。我認為這讓他們對我們提供的臨床數據更有信心。因此，我認為它非常緊密地結合在一起，而且當我們提交 BLA 將臨床數據與從免疫學角度實際發生的情況聯繫起來時，它也會很好地結合起來。

I think we can also say, Mike, and as evidenced by Professor Steinberg's quote in our recent press release around the data, generally, KOLs in the field have been very impressed with the data when we've shared and discussed it with them. I think for them, this is part of going after the Holy Grail of having an effective therapeutic option to treat RRP.

我想我們也可以說，麥克，正如斯坦伯格教授在我們最近的新聞稿中關於數據的引用所證明的那樣，一般來說，當我們與該領域的KOL 分享和討論數據時，他們對這些數據印象深刻。我認為對他們來說，這是追求「聖杯」的一部分，即尋找有效的治療方案來治療 RRP。

Great. That's super helpful. Congrats again on all the progress and thanks for taking our questions.

偉大的。這非常有幫助。再次恭喜所有進展並感謝您提出我們的問題。

Roy Buchanan, Citizens JMP.

羅伊·布坎南，公民 JMP。

Hey. Thanks also for taking the questions. Just maybe just start on 3107 as well. Can you just give maybe some additional detail on the steps that you're envisioning to resolve the manufacturing issues?

嘿。也感謝您提出問題。也許也可以從 3107 開始。您能否提供一些關於您設想解決製造問題的步驟的更多細節？

Hi, Roy. Nice to hear from you. Yeah. So as I outlined on the call, we encountered the issue, the manufacturing issue, earlier on this summer just ahead of our pre-BLA meeting. And we're going through -- and this is an issue with a single use disposable component of our device. We've gone through the steps we need to take to understand the appropriate resolution of that issue, and we're making good progress in implementation. And I think that's all I can really say at the moment.

嗨，羅伊。很高興收到你的來信。是的。正如我在電話會議中概述的那樣，今年夏天早些時候，就在 BLA 會議之前，我們遇到了這個問題，即製造問題。我們正在經歷——這是我們設備的一次性組件的問題。我們已經完成了了解該問題的適當解決方案所需採取的步驟，並且我們在實施方面取得了良好進展。我想這就是我現在能說的全部。

Okay. Fair enough. And then I think this -- correct me if I'm wrong, but the Phase 3 start for 3112 was also gated by resolving this manufacturing issue. Is that correct? The device is approved essentially in Europe, right, with the CE mark? Is it possible that you might be able to start first the Phase 3 in Europe? And when do you think you might be in position to do that, if so?

好的。很公平。然後我想——如果我錯了，請糾正我，但 3112 的第三階段啟動也是透過解決這個製造問題來實現的。這是正確的嗎？該設備基本上已在歐洲獲得批准，對吧，帶有 CE 標誌？你們有可能先在歐洲開始第三階段嗎？如果可以的話，您認為您什麼時候可以這樣做？

Yeah, that's a great question, Roy. So yes, for 3112, starting that Phase 3 trial is dependent on resolving this device issue as well. Mike, do you want to talk about our regulatory interactions in Europe around 3112?

是的，這是一個很好的問題，羅伊。因此，是的，對於 3112 來說，開始第 3 階段試驗也取決於解決該設備問題。Mike，您想談談 3112 年左右我們在歐洲的監管互動嗎？

Yeah. So as we've previously said, we've got alignment from the FDA on the design that we propose for that study. We're in discussions with the EMA, and we're expecting feedback to gain alignment as HPV is a global disease and in most high-income countries, the incidence of throat cancer continues to rise. So we would very much like to run this study in both regions. So we're anxiously awaiting that feedback, and then we can update you on that at the next call.

是的。正如我們之前所說，我們已經從 FDA 獲得了對我們為該研究提議的設計的一致性。我們正在與 EMA 進行討論，並期待得到回饋以取得一致，因為 HPV 是一種全球性疾病，而且在大多數高收入國家，喉癌的發生率持續上升。因此，我們非常希望在這兩個地區進行這項研究。因此，我們正在焦急地等待回饋，然後我們可以在下次通話時向您通報最新情況。

Sudan Loganathan, Stephens.

蘇丹·洛加納森，史蒂芬斯。

Thank you for taking my question. Quick question on the competitive landscape. I think Precigen's 2012, how do you differ from that product? And how do you see the competitive landscape panning out?

感謝您回答我的問題。關於競爭格局的快速問題。我認為 Precigen 的 2012 年產品與該產品有何不同？您如何看待競爭格局的發展？

Yeah, that's a great question. So I'll start off by saying, first of all, we're very confident in the product profile that we see for 3107, and we believe that it has the right profile to be the preferred product of choice for patients and physicians.

是的，這是一個很好的問題。因此，我首先要說的是，首先，我們對 3107 的產品概況非常有信心，我們相信它具有成為患者和醫生首選產品的正確概況。

And the sort of reasons why we believe in that, as Mike discussed earlier on in the call, our ability to drive clinical benefit across the severity of disease across both HPV-6 and -11. And I think this new immunology basis really gives us a very clear idea of exactly how 3107 is doing that.

正如 Mike 之前在電話會議中討論的那樣，我們相信我們有能力在 HPV-6 和 -11 疾病的嚴重程度方面推動臨床效益。我認為這個新的免疫學基礎確實讓我們非常清楚地了解 3107 到底是如何做到這一點的。

So 3107 is a DNA medicine. Precigen's product is based around a gorilla adenovirus. So it's using an adenoviral vector to deliver the gene sequences. And it's difficult to compare the clinical data, because the two trials were conducted in a very different way.

所以3107是一種DNA藥物。Precigen 的產品是基於大猩猩腺病毒。因此它使用腺病毒載體來傳遞基因序列。而且很難比較臨床數據，因為這兩項試驗是以非常不同的方式進行的。

So for 3107, we believe every surgery matters to patients. So we counted every surgery after day zero. And I think in conjunction, Precigen used a somewhat different trial design that allowed scoping and surgery prior to assessment of the efficacy period. So we really took a very different approach.

所以對3107來說，我們相信每一次手術對病人來說都很重要。所以我們在零天之後計算了每一次手術。我認為，Precigen 結合使用了一種稍微不同的試驗設計，允許在評估療效期之前進行範圍界定和手術。所以我們確實採取了一種非常不同的方法。

Mike, anything else you want to add to that sort of calls out the differences between those two products -- product candidates?

麥克，您還想添加什麼其他內容來指出這兩種產品之間的差異——候選產品嗎？

I think fundamentally, they're very different treatment regimen. While we both have four doses, their treatment regimen at week 6 and week 12 includes proactive scoping and removal of any papilloma that is visualized.

我認為從根本上來說，它們是非常不同的治療方案。雖然我們都注射了四劑，但他們在第 6 週和第 12 週的治療方案包括主動觀察和切除任何可見的乳頭狀瘤。

And so if you go back to sort of the message we've heard from patients, every surgery matters. They did see a significant number of surgeries at those week 6 and week 12 time point. And so we do think that's going to impact sort of how other physicians take up the treatment and also how patients might perceive it.

因此，如果你回顧我們從病人那裡聽到的信息，你會發現每一次手術都很重要。他們確實在第 6 週和第 12 週的時間點進行了大量手術。因此，我們確實認為這將影響其他醫生如何接受治療以及患者如何看待它。

Thank you. If I can ask another question. The manufacturing plastic mold and -- would you consider changing the manufacturing? Is that on the table?

謝謝。如果我可以再問一個問題的話。製造塑膠模具－您會考慮改變製造方式嗎？那是在桌子上嗎？

Yeah. So I guess your question relates to the manufacturing issue I mentioned earlier relating to the single-use disposable component of the device. And what we're doing here is we've -- as I mentioned, we believe we've identified the issue and come up with a proposed resolution path. And we're working very closely with the manufacturer of that injection molded component to implement that resolution.

是的。所以我想你的問題與我之前提到的有關該設備的一次性組件的製造問題有關。正如我所提到的，我們在這裡所做的是，我們相信我們已經確定了問題並提出了建議的解決方案。我們正在與該注塑組件的製造商密切合作以實施該決議。

So at the moment, we're not planning on changing manufacturer. We're working very closely with our existing manufacturer to implement that resolution.

所以目前我們不打算更換製造商。我們正在與現有製造商密切合作來實施該決議。

Liang Cheng, Jefferies.

梁誠，杰弗里斯.

Hey, team. Thanks for taking our questions. This is Liang Cheng for Roger from Jefferies.

嘿，團隊。感謝您回答我們的問題。我是 Jefferies 的 Roger 的梁程。

So I guess my first question also about 3107, just wondering any idea about the confirmatory trial, are you still thinking about the same design, or do you envision any implement of redosing in that study? And then also about 3107, the immunology study. So I just wonder, have you looked at the responders versus non-responders? And anything you noticed there? Thanks.

所以我想我的第一個問題也是關於 3107 的，只是想知道關於驗證性試驗的任何想法，您是否仍在考慮相同的設計，或者您是否設想在該研究中實施任何重做？然後還有關於3107，免疫學研究。所以我只是想知道，您是否觀察過響應者與非響應者？你在那裡注意到了什麼嗎？謝謝。

Yeah, that's a great question. So we have talked about the design of our confirmatory trial. Mike, do you want to outline that design and why we decided on it?

是的，這是一個很好的問題。我們已經討論了驗證性試驗的設計。麥克，你想概述一下這個設計以及我們為什麼決定這樣做嗎？

Yeah, absolutely. So in discussions with the agency, they made it very clear if we wanted to have an indication similar to what we used in our Phase 1/2 trial of two surgeries in the preceding year, then the study had to be a placebo-controlled study. And so along with my previous comments with respect to the feedback we've received from Europe, it just made sense to run a randomized study. And we are clearly very confident in the clinical efficacy that we've seen.

是的，絕對是。因此，在與該機構的討論中，他們非常明確地表示，如果我們想要一個類似於我們在前一年兩次手術的1/2 期試驗中使用的適應症，那麼該研究必須是安慰劑對照研究。因此，結合我先前對我們從歐洲收到的回饋的評論，進行一項隨機研究是有意義的。我們顯然對我們所看到的臨床療效非常有信心。

This isn't going to be a particularly large study, about 100 patients. We're going to have a 2:1 randomization and then follow those patients out. We aren't going to include a redosing element into this study at present. And the rationale for that is we have had previous patients treated with an HPV-6-only plasmid that have had efficacy out to 500 and over 800 days. So in discussion with the agency, they were keen for us to have a longer follow-up than we previously had in our Phase 1/2 study.

這不會是一項特別大的研究，大約有 100 名患者。我們將進行 2:1 隨機分組，然後追蹤這些患者。目前我們不打算將重劑量元素納入這項研究。這樣做的理由是，我們之前已經對患者使用了僅 HPV-6 的質粒進行了治療，其療效長達 500 天和 800 天以上。因此，在與該機構的討論中，他們希望我們能夠比先前的 1/2 期研究進行更長的追蹤。

And that was also the motivation for us to run the retrospective study that we'll hopefully -- well, we will report on by the end of the year. So we really do think you need a longer period of time to characterize the benefit of 3107. So that's why we picked our confirmatory study design the way we have.

這也是我們進行回顧性研究的動機，我們希望 - 嗯，我們將在今年年底之前報告。因此，我們確實認為您需要更長的時間來描述 3107 的優勢。這就是為什麼我們選擇這樣的驗證性研究設計。

Thanks, Mike. And I'll just comment briefly on the immunology data, and then I'll ask Matthew to fill in a bit more detail. So yes, absolutely, we looked at responders versus non-responders, and we looked at two sets of samples.

謝謝，麥克。我將簡要評論免疫學數據，然後我將請馬修填寫更多細節。所以，是的，絕對，我們研究了有反應者與無反應者，並且我們觀察了兩組樣本。

The first set of samples were peripheral blood samples that we collected throughout the duration of the trial. And then we also had tissue samples -- so samples taken from the airways prior to treatment and then at the 52-week time period. And these were paired tissue samples taken from the same patients and from the same anatomical location. And we saw a difference in the kinds of immune responses that we saw in responders versus non-responders that we believe corresponds with clinical benefit.

第一組樣本是我們在整個試驗期間收集的周邊血液樣本。然後我們也採集了組織樣本——治療前和 52 週期間從氣道採集的樣本。這些是從同一患者和同一解剖位置採集的成對組織樣本。我們發現反應者與無反應者的免疫反應類型有差異，我們認為這與臨床效益相對應。

But Matthew, do you want to jump in and add some other comments here?

但是馬修，你想在這裡加入一些其他評論嗎？

Sure. Good afternoon. So yes, in addition to what Jacqui has mentioned, the responses within the tissue of the responders is slightly different than that of non-responders with respect to degree of infiltration of T cells, some of the functionality of those T cells and just the overall inflammatory response and interferon alpha and interferon gamma responses that are being observed. And all of these assessments will be further described in the publication that is forthcoming.

當然。午安.所以，是的，除了 Jacqui 提到的之外，在 T 細胞的浸潤程度、這些 T 細胞的一些功能以及總體上，有反應者的組織內的反應與無反應者的反應略有不同。發炎反應以及乾擾素α和乾擾素γ反應。所有這些評估都將在即將出版的出版物中進一步描述。

Thanks. That's very helpful. I guess, also for 3112, just wondering for the ongoing conversation with the EU regulators, what's needed before you -- the trial initiation?

謝謝。這非常有幫助。我想，對於 3112 來說，只是想知道與歐盟監管機構正在進行的對話，在您之前需要什麼——啟動試驗？

Yes. Mike, do you want to comment on that?

是的。麥克，你想對此發表評論嗎？

Yeah. So obviously, the purpose of the interaction is to gain alignment with the overall strategic intent of how we've designed 3112. And I think as we've said previously, we actually used global KOLs in this study design. And so we have a very good representation from Europe. And so we're optimistic that we can gain that alignment. And then just the practical part is we obviously would have to put a clinical trial application into the EMA before we started recruiting patients.

是的。顯然，互動的目的是為了與我們設計 3112 的整體策略意圖保持一致。我認為正如我們之前所說，我們實際上在這項研究設計中使用了全球 KOL。因此，我們有來自歐洲的非常好的代表。因此，我們對能夠實現這種一致性感到樂觀。然後，實際的部分是，在我們開始招募患者之前，我們顯然必須向 EMA 提交臨床試驗申請。

Yi Chen, H.C. Wainwright.

陳毅, H.C.溫賴特。

Hi there. This is [Eduardo] on for Yi. I wanted to -- thanks for taking the question. I was curious if you could offer a little bit more clarity on the timeline for initiating the confirmatory trial for 3107, and how that fits in with the BLA submission that you already expect?

你好呀。這是易建聯的[Eduardo]。我想——感謝您提出問題。我很好奇您能否更清楚地說明啟動 3107 驗證性試驗的時間表，以及這與您已經期望的 BLA 提交情況如何相符？

Yeah. Great question, Eduardo. So as we stated very clearly on the call, we're targeting our BLA submission for mid-2025. We need to start our -- FDA have told us that we need to start our confirmatory trial ahead of commencing that BLA submission. And we're expecting to request rolling submission, priority review as part of that BLA submission. So what I can tell you today is mid-2025.

是的。好問題，愛德華多。因此，正如我們在電話會議中明確指出的那樣，我們的目標是在 2025 年中期提交 BLA。我們需要開始 - FDA 告訴我們，我們需要在開始 BLA 提交之前開始驗證性試驗。我們希望請求滾動提交、優先審查作為 BLA 提交的一部分。所以我今天可以告訴你的是 2025 年中期。

Maybe I'll add a little bit of color around our activities. The FDA has said we needed to commence that study and you know, clearly their rationale for that is often sponsors have not been very forthcoming in delivering their confirmatory studies.

也許我會為我們的活動增添一點色彩。FDA 表示我們需要開始這項研究，你知道，他們這樣做的理由顯然是申辦者通常不太願意提供驗證性研究。

We, however, are at the opposite end of that spectrum. We have almost all our sites identified. We are contracting with sites. We have active IRB submissions. So we will be in a very good position to demonstrate our commitment of delivering on that confirmatory study to the agency.

然而，我們卻處於這個範圍的另一端。我們幾乎已經確定了所有站點。我們正在與網站簽訂合約。我們有積極的 IRB 提交。因此，我們將處於非常有利的位置，向該機構展示我們向該機構提供驗證性研究的承諾。

Yeah. Thank you, Mike. That's a great point. I think we've also really leveraged our experience from our Phase 1/2 study that we conducted in the US, where we worked across eight different clinical trial sites, relief centers that are at the forefront of treating RRP. So I think that experience of working across different sites as well has been very helpful.

是的。謝謝你，麥克。這是一個很好的觀點。我認為我們也真正利用了我們在美國進行的 1/2 期研究的經驗，我們在八個不同的臨床試驗地點和處於治療 RRP 最前沿的救援中心開展工作。因此，我認為跨不同站點工作的經驗也非常有幫助。

Gregory Renza, RBC Capital Markets.

格雷戈里·倫扎（Gregory Renza），加拿大皇家銀行資本市場部。

Hi team. It's Anish on for Greg. Thanks for taking our question. On 3107 and the CELLECTRA device, maybe if you could just remind us the duration of the AEs such as injection site pain and fatigue, how rapidly they were resolved and how this translates to patient and physician expectations when using the CELLECTRA device.

大家好。格雷格的安尼什上場了。感謝您提出我們的問題。關於 3107 和 CELLECTRA 設備，也許您可以提醒我們 AE 的持續時間（例如注射部位疼痛和疲勞）、解決速度有多快以及如何轉化為患者和醫生在使用 CELLECTRA 設備時的期望。

And as you think about the commercial strategy, with Precigen also reporting after the close and suggesting a 2025 launch, how are you thinking about your approach and go-to-market strategy, which could support uptake in the market given the prospects of a competitor already being on the market by the time you would launch? Thanks so much.

當您考慮商業策略時，Precigen 也在收盤後報告並建議 2025 年推出，您如何考慮您的方法和進入市場策略，考慮到競爭對手的前景，這可以支持市場的吸收在您推出時已經在市場上了嗎？非常感謝。

Thanks, Anish. Great questions. So in terms of 3107, as Mike talked about during the call in terms of our combined safety data -- I think, Mike, you can talk about the adverse event profile that we saw and how quickly they resolved?

謝謝，安尼什。很好的問題。因此，就 3107 而言，正如邁克在電話會議期間談到我們的綜合安全數據一樣，我想，邁克，您可以談談我們看到的不良事件概況以及解決問題的速度如何？

Yeah, absolutely. So when you look at the population as a whole, we only had 41% of patients report any treatment-related adverse event. 10 of those were -- 10 out of the 32 patients reported injection site pain. From a grading perspective, only one of those was Grade 2. In fact, the rest of the entire treatment-related adverse events were Grade 1 after that.

是的，絕對是。因此，當你觀察整個人群時，我們只有 41% 的患者報告了任何與治療相關的不良事件。其中 10 名患者中有 10 名報告注射部位疼痛。從等級來看，只有一門是二級。事實上，此後其餘所有與治療相關的不良事件均為 1 級。

And we have data from other electroporation studies that show that the injection site pain associated with the initial administration really falls off in about a sort of 5-, 10-minute timeframe. And as part of our rollout of the device is really going to be around explaining what the patient should expect, how the physician should educate the patient on that, because clearly, this is a new procedure. So half of it is around the unknown.

我們從其他電穿孔研究中獲得的數據表明，與初次給藥相關的注射部位疼痛確實在大約 5 分鐘、10 分鐘的時間內減輕了。作為我們推出該設備的一部分，實際上將圍繞著解釋患者應該期待什麼，醫生應該如何教育患者，因為顯然，這是一個新程序。所以一半是關於未知的。

So as we come to market, we'll very carefully be able to have materials for the patient to know what to expect. And history says that having that level of expectation in place will hopefully further diminish any adverse events associated with electroporation and diminish that injection site pain.

因此，當我們進入市場時，我們將非常仔細地提供材料，讓患者知道會發生什麼。歷史表明，擁有這種水平的期望將有望進一步減少與電穿孔相關的任何不良事件，並減少注射部位的疼痛。

I think it's also very important to note, Mike, is these adverse events are very transient. They resolve very rapidly. And certainly, we hear from patients that the treatment is very tolerable and the healthcare providers tell us that the device is very easy to use. So we think, particularly in a disease like RRP, where it's really having a devastating impact on patients that the rapid resolution of those AEs is going to be very important.

麥克，我認為值得注意的是，這些不良事件非常短暫。他們解決得非常快。當然，我們從患者那裡得知，這種治療的耐受性非常好，而且醫療保健提供者告訴我們，該設備非常易於使用。因此，我們認為，特別是在像 RRP 這樣的疾病中，它確實會對患者產生毀滅性影響，因此快速解決這些 AE 非常重要。

So Anish, does that answer your questions around the 3107 profile? And then we can maybe go on to the '25 launch and go-to-market strategy.

那麼，Anish，這是否回答了您關於 3107 設定檔的問題？然後我們也許可以繼續實施 25 年的發布和上市策略。

That would great. Thanks.

那太好了。謝謝。

Yeah. So as I discussed earlier on in the call, we believe that 3107 has a compelling product profile that will enable it to become the preferred product of choice for the majority of patients and physicians. And I'll hand over to Steve to expand on this in a bit more detail. But it's also -- we've only seen limited data from Precigen to-date.

是的。因此，正如我之前在電話會議中討論的那樣，我們相信 3107 擁有引人注目的產品概況，這將使其成為大多數患者和醫生的首選產品。我將請史蒂夫更詳細地闡述這一點。但迄今為止，我們只看到了 Precigen 的有限數據。

We haven't seen the full data package published yet from the second cohort. So I think we'll be very interested to see that data when it's published. And the difference in the two treatment regimens and approaches, I think, are going to be very interesting. I think our duration data that we expect to be able to announce later on this year is also going to be important. So Steve, do you want to provide your point of view?

我們尚未看到第二批發布的完整資料包。所以我認為當這些數據發佈時我們會非常有興趣看到它。我認為，兩種治療方案和方法的差異將會非常有趣。我認為我們預計將在今年稍後公佈的持續時間數據也很重要。那麼史蒂夫，你想發表你的觀點嗎？

Yeah. So we don't know necessarily that Precigen will be in the market before we will. We'll see kind of how things unfold. But regardless, we do plan to have MSLs out ahead of approval as well as national account managers engaging health plans ahead of approval, which they can do.

是的。因此，我們不一定知道 Precigen 會先於我們上市。我們將會看到事情如何展開。但無論如何，我們確實計劃在批准之前取消 MSL，並讓全國客戶經理在批准之前參與健康計劃，這是他們可以做到的。

We think we've got a well-differentiated product based on the data that we've seen so far. So that's certainly what we'll be focused on. But we know there's tremendous unmet need in the market and the burden around surgeries. As we've talked about, every surgery matters. So as soon as we're able, as soon as we're approved, we will be out there in full force making the case for 3107.

根據迄今為止所看到的數據，我們認為我們已經擁有了一個差異化良好的產品。所以這肯定是我們關注的重點。但我們知道市場上還有巨大的未滿足需求以及手術帶來的負擔。正如我們所討論的，每次手術都很重要。因此，一旦我們有能力，一旦獲得批准，我們將全力支持 3107。

Roy Buchanan, Citizens JMP.

羅伊·布坎南，公民 JMP。

Hey. Thanks for taking the follow-up. It was about the redosing, and you actually answered most of it. But I guess just I think you're going to run a separate trial to look at redosing of 3107, correct? Do you plan to run that in conjunction with the confirmatory trial, or is it going to be sequenced after the conclusion of that trial? Thanks.

嘿。感謝您的關注。這是關於重劑量的問題，實際上你已經回答了大部分問題。但我想你會進行一項單獨的試驗來看看 3107 的重新劑量，對嗎？您是否計劃將其與確認性試驗一起進行，還是將在試驗結束後進行排序？謝謝。

Yeah. Mike, do you want to talk about that redosing approach?

是的。麥克，你想談談重劑量法嗎？

Yeah, absolutely. So we've always thought that the redosing work would be in commercial patients. So we will commence that as sort of as soon as practically possible post launch. And we are thinking that those complete responders potentially could maintain -- at IPVC this week, there's been a lot of talk around can you actually eliminate all the HPV-infected cells, and I think that will be one of the interesting scientific questions that we can look at through continued dosing. But that work is going to take a while, and we'll commence that after commercial launch.

是的，絕對是。所以我們一直認為重劑量工作將針對商業患者。因此，我們將在發布後儘快開始這項工作。我們認為，那些完全反應者可能會維持 - 在本週的 IPVC 上，有很多討論是否可以真正消除所有 HPV 感染的細胞，我認為這將是我們要討論的有趣的科學問題之一。給藥來觀察。但這項工作需要一段時間，我們將在商業發布後開始。

There are no further questions at this time. I will now turn the call back to Jacqui Shea for closing remarks. Please go ahead.

目前沒有其他問題。現在，我將把電話轉回傑奎·謝伊，讓其致閉幕詞。請繼續。

Thank you. The new immunology data that we've discussed today adds to a growing body of evidence that continues to illustrate the potential of 3107 to truly transform the treatment paradigm for patients, who have been living with the devastating effects of RRP. We are mindful of those patients as we remain focused on moving as quickly as possible to meet the key milestones ahead, including publishing the new immunology data, announcing new durability, submitting our BLA, and preparing to be launch-ready at the end of 2025, should we receive approval.

謝謝。我們今天討論的新免疫學數據增加了越來越多的證據，這些證據繼續說明 3107 真正改變患者治療模式的潛力，這些患者一直遭受 RRP 的破壞性影響。我們關心這些患者，因為我們仍然專注於盡快實現未來的關鍵里程碑，包括發布新的免疫學數據、宣布新的耐久性、提交我們的 BLA 以及準備在 2025 年底上市，我們是否應該獲得批准。

At the same time, we're advancing other key candidates and evaluating ways to strengthen our balance sheet to support our work going forward. As we wrap up this year, I'm proud of the important progress we've made in just 12 short months, and we plan to keep that momentum going in the year ahead. Thank you for your attention and good evening, everyone.

同時，我們正在推進其他關鍵候選者，並評估加強我們的資產負債表以支持我們未來工作的方法。在今年結束時，我為我們在短短 12 個月內取得的重要進展感到自豪，我們計劃在未來一年保持這一勢頭。感謝大家的關注，大家晚上好。

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。