Inovio Pharmaceuticals Inc (INO) 2023 Q3 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Inovio third-quarter 2023 financial results conference call. (Operator Instructions) This call is being recorded on Thursday, November 9, 2023. And I would now like to turn the conference over to Mr. Thomas Hong. Thank you. Please go ahead.

女士們、先生們，下午好，歡迎參加 Inovio 2023 年第三季財務業績電話會議。 （操作員說明）本次通話於 2023 年 11 月 9 日星期四進行錄音。我現在將會議轉交給 Thomas Hong 先生。謝謝。請繼續。

Good afternoon and thank you for joining the Inovio 2023 third-quarter conference call. Joining me on today's call are Dr. Jacqui Shea, President and CEO; Dr. Michael Sumner, Chief Medical Officer; Mr. Mark Twyman, Chief Commercial Officer; and Mr. Peter Kies, Chief Financial Officer.

下午好，感謝您參加 Inovio 2023 年第三季電話會議。與我一起參加今天電話會議的還有總裁兼執行長 Jacqui Shea 博士；邁克爾·薩姆納博士，首席醫療官； Mark Twyman 先生，商務長；以及財務長 Peter Kies 先生。

Today's call will review our corporate and financial information for the quarter ended September 30, 2023, as well as provide a development progress update for our DNA medicines platform. Following prepared remarks, we will conduct a question-and-answer segments.

今天的電話會議將審查我們截至 2023 年 9 月 30 日的季度的公司和財務信息，並提供我們 DNA 藥物平台的開發進度更新。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 include clinical and regulatory developments and timing of clinical data readouts along with capital resources and strategic matters. All of these statements are based on the beliefs and expectations of management as of today. Actual events or results could differ materially.

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。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。實際事件或結果可能有重大差異。

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

我們請您參考我們不時向 SEC 提交的文件，這些文件在“風險因素”標題下指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新聞稿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。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. Over the last few months, I'm delighted to say that we've made significant progress advancing our lead candidate, INO-3107 for the treatment of recurrent respiratory papillomatosis or RRP. Of the two very important regulatory developments. We are closer than ever to delivering on the promise of DNA medicines to patients and bringing the first DNA medicine to market in the United States.

下午好，感謝大家參加今天的電話會議。在過去的幾個月裡，我很高興地說，我們在推進用於治療復發性呼吸道乳頭狀瘤病或 RRP 的主要候選藥物 INO-3107 方面取得了重大進展。這兩項非常重要的監理進展。我們比以往任何時候都更接近向患者兌現 DNA 藥物的承諾，並將第一個 DNA 藥物推向美國市場。

Specifically, in the third quarter of 2023, the FDA granted breakthrough therapy designation to INO-3107 based on clinical evidence indicating that it may demonstrate substantial improvement over existing therapies for RRP. A couple of weeks following that breakthrough therapy designation, we received feedback from the FDA that data from our completed Phase 1/2 two trial of 3107 could be used to support submission of a biological license application or BLA for review on the FDA's Accelerated Approval Program.

具體而言，2023 年第三季度，FDA 授予 INO-3107 突破性療法稱號，因為臨床證據表明 INO-3107 可能比現有的 RRP 療法有實質改善。在獲得突破性療法指定幾週後，我們收到了 FDA 的回饋，即我們已完成的 3107 1/2 期二期試驗的數據可用於支持提交生物許可申請或 BLA，以供 FDA 加速審批計劃審查。

Our Chief Medical Officer, Mike Sumner, will provide more context shortly, but this news means that we no longer need to complete a Phase 3 trial before BLA submission and will ultimately allow for a potentially much faster development pathway. We will, however, be required to initiate confirmatory trial and satisfy all other FDA filing requirements prior to BLA submission as is usual for the accelerated approval pathway.

我們的首席醫療官 Mike Sumner 很快將提供更多背景信息，但這一消息意味著我們不再需要在提交 BLA 之前完成第 3 階段試驗，並且最終將實現可能更快的開發途徑。然而，我們將被要求在提交 BLA 之前啟動驗證性試驗並滿足 FDA 的所有其他備案要求，這對於加速審批途徑來說是常見的。

To achieve that, our team has already submitted a request for an initial comprehensive multidisciplinary breakthrough therapy meeting to the FDA for the fourth quarter. This meeting will help further align our plans with the FDA and determine the timing for critical deliverables associated with our BLA submission.

為了實現這一目標，我們的團隊已向 FDA 提交了在第四季度召開初步綜合多學科突破性治療會議的請求。這次會議將有助於進一步調整我們與 FDA 的計劃，並確定與我們的 BLA 提交相關的關鍵交付成果的時間。

As we make progress on this new expedited pathway, we have every intention to utilize the opportunity for increased communication with the FDA and other advantages offered by breakthrough therapy designation such as requesting a rolling submission of completed sections for BLA under priority review of the fully submitted BLA. As a result of this new timeline, we have accelerated our commercialization strategy to be prepared to launch 3107 should it be approved led by Mark Twyman, our Chief Commercial Officer, whom you'll hear from shortly.

隨著我們在這一新的快速途徑上取得進展，我們完全打算利用與 FDA 加強溝通的機會以及突破性療法指定提供的其他優勢，例如要求滾動提交 BLA 的完整部分，並優先審查完整提交的部分布拉。由於這一新的時間表，我們加快了我們的商業化策略，準備在 3107 得到我們首席商務官 Mark Twyman 領導的批准後推出，您很快就會收到他的消息。

Our commercial team has extensive experience bringing products to market, including innovative new technologies and products in the rare disease space. Mark will spend a few moments today talking about his team's current efforts to expedite building a number of critical capabilities and establishing pathways for commercial success, such as creating the value proposition for 3107, putting in place an optimized distribution model, developing payer, specialty pharmacy and pharmacy benefit management strategies to ensure favorable access, and preparing to stand up a field organization.

我們的商業團隊擁有將產品推向市場的豐富經驗，包括罕見疾病領域的創新新技術和產品。馬克今天將花一些時間談論他的團隊目前為加快構建一些關鍵能力和建立商業成功途徑所做的努力，例如為 3107 創建價值主張、建立優化的分銷模式、開發付款人、專業藥房和藥品福利管理策略，以確保有利的獲取，並準備建立一個現場組織。

Mark and his commercial leadership team brings decades of combined biopharmaceutical experience from such companies as Sanofi-Genzyme, Merck, CSL Behring, and MedImmune. They've been personally involved in nearly every aspect of successfully commercializing products from sales and marketing to distribution, market access, and government affairs. I'm really pleased with the progress of this team as they worked hand in glove with leaders from across the company to optimize the launch plan for our lead candidate.

Mark 和他的商業領導團隊帶來了賽諾菲-健贊 (Sanofi-Genzyme)、默克 (Merck)、CSL Behring 和 MedImmune 等公司數十年的生物製藥經驗。他們親自參與了產品成功商業化的幾乎所有方面，從銷售和行銷到分銷、市場准入和政府事務。我對這個團隊的進展感到非常滿意，因為他們與全公司的領導者密切合作，優化了我們主要候選人的發布計劃。

In addition to the regulatory achievements and commercial readiness efforts I've described, we've worked very hard over the past 18 months or so to restructure our corporate organization with the goal of meeting our current focused pipeline needs and reducing spending, while at the same time retaining and building the expertise critical to implement our plans for our late-stage pipeline. After many difficult months and quarters, I'm pleased to see the collective efforts of our dedicated and experienced cross-functional team make a real difference.

除了我所描述的監管成就和商業準備工作之外，我們在過去 18 個月左右的時間裡還非常努力地重組我們的公司組織，其目標是滿足我們當前的重點管道需求並減少支出，同時在同時保留和建立對實施我們的後期管道計劃至關重要的專業知識。經過許多困難的月份和季度後，我很高興看到我們敬業且經驗豐富的跨職能團隊的集體努力產生了真正的影響。

With that, I'd like to turn it over to our Chief Medical Officer, Dr. Mike Sumner to provide a brief overview of the regulatory and development progress we've achieved, 3107; the next steps on our accelerated development time line; and other key preparations to support the BLA submission; and if approved, to bring this candidate to market. Mike?

說到這裡，我想將其交給我們的首席醫療官 Mike Sumner 博士，簡要概述我們所取得的監管和開發進展，3107；我們加速開發時間表的後續步驟；以及支援 BLA 提交的其他關鍵準備工作；如果獲得批准，將該候選人推向市場。麥克風？

Thank you very much, Jacqui and greetings, everyone. As Jacqui has mentioned, we have made substantial progress with our lead candidate, INO-3107. To provide a little perspective on how far this candidate has been advancing through development, we've created this timeline. We started our Phase 1/2 trial in 2020, the same year the FDA granted orphan drug status.

非常感謝 Jacqui，並向大家問好。正如 Jacqui 所提到的，我們在主要候選藥物 INO-3107 方面取得了實質進展。為了讓大家了解候選人在開發過程中所取得的進步，我們創建了這個時間表。我們於 2020 年開始 1/2 期試驗，同年 FDA 授予孤兒藥物地位。

After announcing positive final results from the trial earlier this year. the European Commission granted orphan drug status in May, followed by the FDA's Breakthrough Therapy Designation in September. Shortly thereafter, we received important feedback that data from our completed Phase 1/2 trial could support submission of a BLA for review under the FDA's Accelerated Approval Program.

今年早些時候宣布試驗的積極最終結果後。歐盟委員會於 5 月授予孤兒藥地位，隨後 FDA 於 9 月授予突破性療法稱號。此後不久，我們收到了重要回饋，即我們已完成的 1/2 期試驗的數據可以支持提交 BLA 以供 FDA 加速審批計劃下的審查。

To take a candidate from proof of concept to working on a filing -- foot to filing a BLA in the span of three years is lightning speed and speaks to the hard work and collaboration of the broader Inovio team. Looking ahead, the opportunity to file our BLA under the Accelerated Approval Program assures that our team will need to continue to run fast and hard.

在三年的時間裡，候選人從概念驗證到提交申請，再到提交 BLA，速度之快堪稱閃電，這體現了更廣泛的 Inovio 團隊的辛勤工作和協作。展望未來，根據加速審批計劃提交 BLA 的機會確保我們的團隊需要繼續快速且努力地運作。

I'd like to speak briefly as to why we have been granted the opportunity to submit a BLA for 3107 under the FDA's Accelerated Approval Program. First, keep in mind that the FDA instituted its Accelerated Approval Program to allow for early approval of drugs that treat serious conditions and fill an unmet medical need. Additionally, they have recently issued a press release identifying their desire to utilize this program to further accelerate the development of rare disease therapies.

我想簡單談談為什麼我們有機會根據 FDA 的加速審批計劃提交 3107 的 BLA。首先，請記住，FDA 制定了加速審批計劃，以便儘早批准治療嚴重疾病和滿足未滿足的醫療需求的藥物。此外，他們最近發布了一份新聞稿，表明他們希望利用該計劃進一步加速罕見疾病療法的開發。

In general to qualify a drug candidate must address a serious or life-threatening condition with consideration for the severity, rarity or prevalence of the condition and available treatment options. For those who are not familiar with RRP, and I must include myself in this category before coming to Inovio last year, it's a debilitating and rare disease caused primarily by HPV 6 and/or HPV 11.

一般來說，要獲得資格，候選藥物必須解決嚴重或危及生命的病症，同時考慮病症的嚴重性、罕見性或普遍性以及可用的治療方案。對於那些不熟悉 RRP 的人來說，我必須在去年來到 Inovio 之前將自己納入這一類別，這是一種使人衰弱的罕見疾病，主要由 HPV 6 和/或 HPV 11 引起。

RRP is characterized by the development of small, wart-like growth or papillomas in the upper respiratory tract. While these papilloma as a generally benign, they can cause severe life-threatening airway obstruction and respiratory complications. The majority of patients with RRP need to undergo multiple surgeries year after year to remove the recurring papillomas. This has a significant impact on quality of life, coupled with the potential for long-term impact on vocal cords, which can limit the patient's ability to speak effectively.

RRP 的特徵是上呼吸道出現小的疣狀生長物或乳頭狀瘤。雖然這些乳頭狀瘤通常是良性的，但它們可能會導致嚴重危及生命的氣道阻塞和呼吸系統併發症。大多數 RRP 患者需要年復一年地接受多次手術以切除復發的乳頭狀瘤。這對生活品質產生重大影響，並且可能對聲帶產生長期影響，從而限制患者有效說話的能力。

We are pleased that the FDA has now recognized the impact this devastating disease has on patients' lives and awareness that in large part is due to the persistent efforts of RRP Foundation, a patient advocacy organization that has been working tirelessly to raise the need for better and less invasive treatments. This links with another characteristic required to qualify for the Accelerated Approval Program, which is that the drug candidate must provide a meaningful advantage over other available therapies. In this instance, the standard of care for RRP, as I mentioned, is repeat surgeries to remove the papillomas from the throat and vocal cords.

我們很高興FDA 現已認識到這種毀滅性疾病對患者生活和意識的影響，這在很大程度上要歸功於RRP 基金會的不懈努力，RRP 基金會是一個患者倡導組織，一直在不知疲倦地努力提高對更好的治療的需求。以及侵入性較小的治療。這與獲得加速審批計劃資格所需的另一個特徵有關，即候選藥物必須提供優於其他可用療法的有意義的優勢。在這種情況下，正如我所提到的，RRP 的護理標準是重複手術以去除喉嚨和聲帶上的乳頭狀瘤。

I'm pleased to say that in our completed Phase 1/2 study, 81% of patients experienced a reduction in the number of surgeries in the year after treatment versus the year prior to treatment. This included nine patients representing 28% of patients in the study who do not require any surgeries following treatment initiation. Further, our immunology data provides a potential mechanism of action, which supports the clinical evidence, which I will highlight next.

我很高興地說，在我們已完成的 1/2 期研究中，81% 的患者在治療後一年的手術次數比治療前一年有所減少。其中包括 9 名患者，佔研究中患者的 28%，他們在治療開始後不需要任何手術。此外，我們的免疫學數據提供了一種潛在的作用機制，支持臨床證據，我接下來將重點介紹這一點。

This slide helps illustrate the scope and impact of the immune response in the natural patient who had undergone six surgeries the year prior to the trial followed by zero surgeries during the trial. The graphs on the left here depict the CD8 T cell response observed in this patient before and after completion of dosing. As you can see, this patient experienced a strong induction of HPV specific CD8 T cells that have markers of cellular activation and a positive for granzymes and perforin, which are known to be key mediators of eliminating virally infected cells by killer T cells.

這張投影片有助於說明自然患者免疫反應的範圍和影響，該患者在試驗前一年接受了六次手術，隨後在試驗期間進行了零次手術。左圖描繪了該患者在給藥前後觀察到的 CD8 T 細胞反應。如您所看到的，該患者經歷了HPV 特異性CD8 T 細胞的強烈誘導，這些細胞具有細胞活化標記，顆粒酶和穿孔素呈陽性，而已知顆粒酶和穿孔素是殺傷性T 細胞消除病毒感染細胞的關鍵介質。

The data in both graphs indicate that 3107 expanded these critically important cells in impressive fashion with the most highly active killer T cells, which are those showing expression of all three activation markers exhibiting close to a ten-fold increase in frequency. It is these types of cells that we believe are key contributors to reduction in the need for surgery, exemplified in photos on the right-hand side of the slide.

兩張圖中的數據表明，3107 以令人印象深刻的方式擴增了這些極其重要的細胞，其中包括活性最高的殺傷 T 細胞，這些細胞顯示所有三種活化標記的表達頻率增加了接近十倍。我們相信這些類型的細胞是減少手術需求的關鍵因素，如幻燈片右側的照片所示。

These are images of the same patients' vocal cords before and after treatment with 3107. Again, this patient went from having six surgeries in the year prior to treatment to zero surgeries in the 12 months following the first dose. As you can imagine that level of reduction in surgeries has an incredible impact on the patient, but it is important to highlight that RRP patients and their health care providers have indicated time and again, that a reduction of even one surgery would provide significant improvement in quality of life.

這些是同一患者在使用 3107 治療前後的聲帶影像。同樣，該患者在治療前一年內進行了 6 次手術，在第一次用藥後的 12 個月內減少了零次手術。正如您可以想像的那樣，手術次數的減少對患者產生了令人難以置信的影響，但重要的是要強調RRP 患者及其醫療保健提供者一再表示，即使減少一次手術也會顯著改善患者的病情。生活品質。

One important note about our trial design. While our treatment involves four doses over nine weeks, what we call the treatment window, we counted any surgery conducted after the first dose. We did not wait until after all four doses were administered to start counting surgeries. The rationale behind this is important.

關於我們的試驗設計的一個重要說明。雖然我們的治療涉及九週內的四次劑量，即我們所說的治療窗口，但我們計算了第一次劑量後進行的所有手術。我們沒有等到所有四劑注射完畢後才開始統計手術次數。這背後的理由很重要。

As I stated above, patients care about every single surgery regardless of when it happens, whether it happens during the treatment window or not because each and every surgery impacts that patient's life. These results add to the growing body of evidence that our DNA medicines candidate are well-tolerated immunogenic, and particularly adept at promoting viral clearance and lesion regression in HPV related diseases.

正如我上面所說，患者關心每一次手術，無論它何時發生，是否在治療窗口期間發生，因為每一次手術都會影響患者的生活。這些結果進一步證明我們的 DNA 候選藥物具有良好的免疫原性耐受性，並且特別擅長促進 HPV 相關疾病的病毒清除和病變消退。

From a regulatory standpoint, we now have several key objectives ahead. We have submitted our request for an initial comprehensive multidisciplinary breakthrough therapy meeting and have asked the FDA for it to take place in the fourth quarter of this year. At that meeting, we will discuss key elements of our plan future submission for an accelerated approval review, including required immunology data, key CMC plans, including process performance qualification or PPQ strategy, alignment on questions about CELLECTRA delivery device, and other clinical strategy steps.

從監管的角度來看，我們現在有幾個關鍵目標。我們已經提交了召開首次綜合多學科突破性治療會議的請求，並要求 FDA 在今年第四季度舉行會議。在那次會議上，我們將討論未來提交加速審批審查計劃的關鍵要素，包括所需的免疫學數據、關鍵CMC 計劃（包括工藝性能鑑定或PPQ 策略）、有關CELLECTRA 輸送設備問題的協調以及其他臨床策略步驟。

The outcome of this meeting will be instructive to the timeline of critical deliverables for the BLA submission. Shortly thereafter, we plan to submit our protocol for a confirmatory trial to the FDA drawing on our previous alignment with the agency on study design. Under accelerated approval, a confirmatory study is always required to verify the anticipated clinical benefit of a candidate, and we have been requested to initiate this trial prior to BLA submission.

這次會議的結果將對 BLA 提交的關鍵交付成果的時間表具有指導意義。此後不久，我們計劃借鑒我們先前與該機構在研究設計方面的一致意見，向 FDA 提交驗證性試驗方案。在加速批准下，始終需要進行驗證性研究來驗證候選者的預期臨床益處，並且我們被要求在提交 BLA 之前啟動這項試驗。

Throughout the process of submitting our BLA under the accelerated approval program, we will utilize the benefits of our Breakthrough Therapy Designation status, which affords priority access to the FDA's guidance and advice to trying to quickly resolve any outstanding questions. We also plan to take advantage of the opportunity to submit under the FDA's rolling review program and plan to request a priority review once the BLA is fully submitted which has the potential to further accelerate the product development time line.

在根據加速審批計劃提交 BLA 的整個過程中，我們將利用我們的突破性療法指定狀態的優勢，該狀態可以優先獲得 FDA 的指導和建議，以嘗試快速解決任何懸而未決的問題。我們還計劃利用根據 FDA 滾動審查計劃提交的機會，並計劃在 BLA 完全提交後請求優先審查，這有可能進一步加快產品開發時間。

Rolling review allows for a company to submit completed sections of a BLA for review by the FDA generally over a three month window rather than waiting until every section is completed to submit. Under priority review, the FDA aims to take an action on the application within 6 months compared to 10 months under standard review.

滾動審查允許公司在三個月內提交 BLA 的完整部分供 FDA 審查，而不是等到每個部分完成後再提交。在優先審查下，FDA 的目標是在 6 個月內對申請採取行動，而標準審查則需要 10 個月。

It's important to recognize that achieving an approval of our BLA requires a team with expertise across an array of functions. We are fortunate to be working with such an incredible team of experts who bring with them years of price success in advancing innovative medicines through approval to commercialization with the ultimate goal of benefiting patients.

重要的是要認識到，獲得 BLA 的批准需要一支具有跨職能專業知識的團隊。我們很幸運能夠與這樣一支令人難以置信的專家團隊合作，他們在推動創新藥物通過批准商業化方面取得了多年的價格成功，最終目標是造福患者。

Every one of the functions I've listed here on the slide is critical, but just to give you a sense of one important area has underway, our medical affairs function is focused on developing and implementing plans for scientific engagement, medical communications, and field operations. The work done by medical affairs is an important juncture between those who work to develop medicines and our partners in commercial who make sure that patients can ultimately receive them. With that, I'll now turn the call over to our Chief Commercial Officer, Mark Twyman, for some important updates on how our commercial team is working to ensure just that. Mark?

Every one of the functions I've listed here on the slide is critical, but just to give you a sense of one important area has underway, our medical affairs function is focused on developing and implementing plans for scientific engagement, medical communications, and field營運.醫療事務部門所做的工作是藥物開發人員與確保患者最終能夠接受藥物的商業夥伴之間的重要結合點。現在，我將把電話轉給我們的首席商務官 Mark Twyman，了解我們的商務團隊如何努力確保這一點的一些重要更新。標記？

Thanks, Mike. Before I jump into the specifics of our commercial strategy, I'd just like to say it is a pleasure to have the opportunity to speak with you all today and how excited I am about the prospects for INO-3107. While this is my first time on a quarterly financial call for Inovio, I have been with the company for about six years. And As Jacqui mentioned earlier, I've been involved in the commercialization of biopharmaceutical products for many years for both small and large companies as has my team. We are extremely excited to begin implementing many of the plans we have been working on to benefit patients who are in desperate need of options to improve their quality of life.

謝謝，麥克。在詳細介紹我們的商業策略之前，我想說很高興今天有機會與大家交談，並且我對 INO-3107 的前景感到非常興奮。雖然這是我第一次參加 Inovio 的季度財務電話會議，但我已經在該公司工作了大約六年。正如 Jacqui 之前提到的，我和我的團隊一樣，多年來一直為小型和大型公司參與生物製藥產品的商業化。我們非常高興能夠開始實施我們一直在努力的許多計劃，以使那些迫切需要改善生活品質的患者受益。

Let's take a few minutes to discuss what we believe are five key areas to achieve success in the launch of an orphan drug. The first is to create a long-term commercial strategy by starting early and continuously updating based on end-market data. It is also important to build up the required resources as early as possible before regulatory approval is granted.

讓我們花幾分鐘時間討論一下我們認為孤兒藥上市成功的五個關鍵領域。首先是儘早開始並根據終端市場數據不斷更新來制定長期商業策略。在獲得監管部門批准之前儘早建立所需的資源也很重要。

As I mentioned, I've been at Inovio for several years helping the company prepare to bring DNA medicines to market. We now have the opportunity to leverage existing cross-functional capabilities for the development and potential launch of INO-3107. Next key element to a successful launch of an orphan drug is demonstrating the value of your product to all stakeholders. This value proposition has to be provided in the context of any competition in a much leveraged trial data in real world evidence.

正如我所提到的，我在 Inovio 工作了幾年，幫助該公司準備將 DNA 藥物推向市場。我們現在有機會利用現有的跨職能能力來開發和潛在推出 INO-3107。成功推出孤兒藥的下一個關鍵要素是向所有利害關係人展示產品的價值。這項價值主張必須在現實世界證據中充分利用試驗數據的任何競爭背景下提供。

Next, a company that successfully launched the biopharmaceutical product must ensure that patients have a voice in their care and the options offered. This is accomplished by involving patients and patient organizations early in the development process. As Mike mentioned, the RRP Foundation has done a wonderful job in advocating for patients with RRP over the years, sharing their experiences with regulators and policymakers alike. We are proud to consult with them on our shared goal to help patients suffering from this debilitating and serious disease.

接下來，成功推出生物製藥產品的公司必須確保患者在他們的護理和所提供的選擇中擁有發言權。這是透過在開發過程的早期讓患者和患者組織參與來實現的。正如 Mike 所提到的，RRP 基金會多年來在為 RRP 患者提供支援方面做得非常出色，與監管機構和政策制定者分享了他們的經驗。我們很榮幸能夠與他們就我們的共同目標進行磋商，以幫助患有這種使人衰弱的嚴重疾病的患者。

The fourth key element is to take an active role in disease education to details stakeholder activity plan. This includes sending medical liaisons into the field early and creating innovative sales roles such as patient-centric field reps. And last, but probably most importantly, is to get the supply chain up to speed as quickly as possible. This includes determining the appropriate distribution strategy model for INO-3107, identifying and selecting supply chain partners in really understanding that last mile logistics for the product, a complete manufacture to patient solutions.

第四個關鍵要素是在疾病教育中發揮積極作用，詳細說明利害關係人的活動計劃。這包括儘早派遣醫療聯絡員到現場並創建創新的銷售角色，例如以患者為中心的現場代表。最後，但也可能最重要的一點是，盡快讓供應鏈加快速度。這包括確定 INO-3107 適當的分銷策略模型，識別和選擇供應鏈合作夥伴，真正了解產品的最後一哩物流，從製造到患者的完整解決方案。

It's important to note that INO-3107 does not require ultra cold or frozen storage or following prior to injection and refrigerator stable at two to eight degrees Celsius, which will be key factors for both distribution and administration. I'm pleased to report that for INO-3107, many of the key areas for success I just outlined are underway are being addressed.

值得注意的是，INO-3107 不需要超冷或冷凍儲存，也不需要注射前和冰箱穩定在 2 到 8 攝氏度，這將是分配和給藥的關鍵因素。我很高興地報告，對於 INO-3107，我剛才概述的許多成功關鍵領域正在解決。

For example, we are actively engaging external partners and service providers and have started implementing plans for product distribution and logistics, payer engagement and reimbursement, specialty pharmacy identification, patient and provider awareness and education, customer service programs, and other sales and marketing activities. It's also worth noting, we believe that INO-3107 will be considered by payers to be a specialty pharmacy product not a buy-and-bill product, consistent with many other orphan disease treatments.

例如，我們正在積極與外部合作夥伴和服務提供者合作，並開始實施產品分銷和物流、付款人參與和報銷、專業藥房識別、患者和提供者意識和教育、客戶服務計劃以及其他銷售和行銷活動的計劃。另外值得注意的是，我們相信 INO-3107 將被付款人視為一種特殊藥品產品，而不是購買和計費產品，這與許多其他孤兒疾病治療方法一致。

We are also continuing to deepen our understanding of RRP as a disease, the treatment paradigm in the United States and impact of both the disease and the current surgical treatment regimen on patients. We have taking extra care to really understand the needs of patients, doctors, caretakers, and advocates to inform our path forward.

我們也持續加深對 RRP 作為疾病、美國的治療範例以及該疾病和當前手術治療方案對患者的影響的理解。我們特別注意真正了解患者、醫生、護理人員和倡導者的需求，為我們的前進道路提供資訊。

Here's a high-level snapshot of what we understand so far. RRP is a chronic, rare disease caused by HPV 6 and HPV 11. The current standard of care surgery with many patients facing a lifetime of repeated surgeries as their only option. Incidence and prevalence of RRP is variable globally and depends on several factors.

這是我們迄今為止所了解的高級快照。 RRP 是一種由 HPV 6 和 HPV 11 引起的慢性罕見疾病。目前的護理標準手術是許多患者一生中唯一的選擇，面臨重複手術。 RRP 的發生率和盛行率在全球範圍內各不相同，並且取決於多種因素。

The most widely cited US epidemiology data estimated that there were 14,000 active cases in about 1.8 per 100,000 new cases in adults each year. Our recent publication sites said on average patients with RRP undergo about four surgeries per year. These surgeries and surrounding care put tremendous financial burden on patients and the healthcare system.

最廣泛引用的美國流行病學數據估計，每年有 14,000 例活躍病例，每 10 萬名成人新病例中約有 1.8 例。我們最近的出版網站稱，RRP 患者平均每年接受約四次手術。這些手術和周圍護理給患者和醫療保健系統帶來了巨大的經濟負擔。

Based on ongoing market research, we believe that laryngologist are the primary health care providers treating patients suffering from this condition that they are comfortable administering drugs and utilizing new tools and devices. In our discussions with them, they have expressed particular interest in finding a more effective nonsurgical treatment option for the RRP patients.

根據正在進行的市場研究，我們認為喉科醫生是治療患有這種疾病的患者的主要醫療保健提供者，他們能夠輕鬆地服用藥物並使用新的工具和設備。在我們與他們的討論中，他們表示特別有興趣為 RRP 患者尋找更有效的非手術治療選擇。

We estimate that about 300 to 400 laryngologist in the US conducted majority of RRP surgical procedures. We are currently in the process of validating those estimates and geographically mapping their practice locations to support final decisions about the size and alignment of our field-based sales team for INO-3107. Key opinion leaders estimate that approximately one-half of all the laryngologist practice and academic institutions. In recent discussions with RRP patients, we heard that many of them prefer to be treated at these regional academic centers.

我們估計，美國約有 300 至 400 名喉科醫生實施了大部分 RRP 手術。我們目前正在驗證這些估計值並繪製其實踐位置的地理地圖，以支援 INO-3107 現場銷售團隊的規模和調整的最終決策。關鍵意見領袖估計，大約有一半的喉科醫生從事實務和學術機構。在最近與 RRP 患者的討論中，我們聽說他們中的許多人更喜歡在這些區域學術中心接受治療。

As I've outlined today, we're consider every detail that can impact patients, healthcare providers, and ultimately, our commercial strategy as we work to potentially bring INO-3107 to market. We will continue drawing on the strength of the Inovio team across functions and working with seasoned partners to meet the demands of this accelerated timeline and deliver on the promise of DNA medicine. I'll now turn the call back to our CEO, Jacqui Shea for a pipeline update. Jacqui?

正如我今天所概述的，當我們努力將 INO-3107 推向市場時，我們正在考慮可能影響患者、醫療保健提供者以及最終影響我們商業策略的每一個細節。我們將繼續利用 Inovio 跨職能團隊的力量，並與經驗豐富的合作夥伴合作，以滿足這項加速時間表的需求，並兌現 DNA 醫學的承諾。現在，我將把電話轉回給我們的執行長 Jacqui Shea，以了解管道更新情況。雅基？

Thank you, Mark. Before I cover some additional updates from our pipeline, I'd like to take a moment to reiterate some of the key takeaways from what you've heard today from Mike and Mark, which highlight why we believe in the commercial potential of 3107 and its ability to potentially transform the treatment paradigm for RRP.

謝謝你，馬克。在介紹我們的產品線的一些其他更新之前，我想花點時間重申一下您今天從 Mike 和 Mark 那裡聽到的一些關鍵要點，這些要點強調了為什麼我們相信 3107 的商業潛力及其有能力改變RRP的治療模式。

In our completed Phase 1/2 trial, 3107 was able to generate antigen-specific T cell responses against both HPV 6 and HPV 11, a result that was observed in patients across the spectrum of disease severity. We also saw reduction in surgery in HPV 6 and HPV 11 positive patients, again across the spectrum of disease severity.

在我們完成的 1/2 期試驗中，3107 能夠產生針對 HPV 6 和 HPV 11 的抗原特異性 T 細胞反應，這一結果在各種疾病嚴重程度的患者中觀察到。我們也發現 HPV 6 和 HPV 11 陽性患者的手術數量有所減少，同樣是在疾病嚴重程度範圍內。

3107 was well tolerated by participants in the trial resulting in mostly low-grade treatment-emergent adverse effects such as injection site pain and fatigue. I'll cover T cell generation platforms. 3107 and DNA medicines in general don't cause an antibacterial response, which means that 3107 could potentially be administered over time to boost the immune response if needed. Because RRP is a chronic viral disease that can lead persistent reoccurring symptoms, re administration may be an important factor in extending efficacy for a lifetime, and we anticipate exploring that opportunity further if 3107 is approved.

試驗參與者對 3107 的耐受性良好，導致大多數治療引起的低度不良反應，例如注射部位疼痛和疲勞。我將介紹 T 細胞生成平台。 3107 和 DNA 藥物一般不會引起抗菌反應，這意味著如果需要，可以隨著時間的推移使用 3107 以增強免疫反應。由於 RRP 是一種慢性病毒性疾病，可導致持續性復發症狀，因此重新給藥可能是延長終生療效的重要因素，如果 3107 獲得批准，我們預計將進一步探索此機會。

Thinking further down the line to potential use in market, it's important to reiterate the point that Mark made earlier. 3107 is refrigerator stable at two to eight degrees Celsius, does not require frozen or ultra cold storage and will be packaged in a single use vial, all of which will be key factors in distribution and administration. We see INO-3107 as an exemplar of the larger potential of our DNA medicines platform, and we remain dedicated to driving progress across our pipeline to unlock that potential for patients across the globe.

進一步思考市場的潛在用途，重申馬克先前提出的觀點很重要。 3107 在攝氏 2 至 8 度的冰箱中穩定，不需要冷凍或超低溫儲存，並將包裝在一次性小瓶中，所有這些都將是分銷和管理的關鍵因素。我們將 INO-3107 視為我們 DNA 藥物平台更大潛力的典範，我們將繼續致力於推動整個管道的進展，為全球患者釋放這一潛力。

We believe that this is achievable in the three-step process. As you can see on this slide, in the near term, Inovio is focused on optimizing the opportunity for 3107 as a potential treatment for RRP patients. In the midterm, Inovio is working to advance eight other clinical-stage candidates targeting HPV related diseases, cancers, and infectious diseases. But the longer term and every year is developing next-generation DNA medicine technology, including DNA-encoded monoclonal antibodies or dMAb targeting COVID-19 as well as DNA launched nanoparticles or dLNPs, targeting infectious disease targets and cancer vaccines that have various disease targets.

我們相信，透過三步驟過程可以實現這一目標。正如您在這張投影片中所看到的，短期內，Inovio 的重點是優化 3107 作為 RRP 患者潛在治療的機會。在中期，Inovio 正在努力推進其他八種針對 HPV 相關疾病、癌症和傳染病的臨床階段候選藥物。但從長遠來看，每年都在開發下一代DNA 醫學技術，包括針對COVID-19 的DNA 編碼單株抗體或dMAb，以及針對傳染病目標和具有各種疾病目標的癌症疫苗的DNA 發射奈米顆粒或dLNP。

This slide provides greater detail on our pipeline. Obviously, 3107 is closest to market, but we also have several key candidates that we're working to advance. In particular, we're finalizing the study reports and data analysis on INO-5401 for treatment of newly diagnosed glioblastoma and continue to support treatment for some patients on the trial.

這張投影片提供了有關我們管道的更多詳細資訊。顯然，3107 最接近市場，但我們也有幾個正在努力推進的關鍵候選人。特別是，我們正在最終確定 INO-5401 用於治療新診斷的膠質母細胞瘤的研究報告和數據分析，並繼續支持對一些試驗患者的治療。

We're currently in discussions about next steps with KOLs and our partner, Regeneron. And then excellent example of the versatility of our DNA medicine candidates, INO-5401, is also being studied in a Phase Ib investigator-sponsored trial by the University of Pennsylvania's vaccine center.

我們目前正在與 KOL 和我們的合作夥伴 Regeneron 討論後續步驟。然後，我們的 DNA 候選藥物 INO-5401 的多功能性的一個很好的例子，也在賓州大學疫苗中心進行的 Ib 期研究人員贊助的試驗中進行研究。

Researchers that are evaluating 5401 in patients with BRCA1 or BRCA2 gene mutations. This vaccine candidate may have the potential to prevent breast cancer for people with those mutations. The research was recently featured on the Today Show highlighting both the potential of DNA medicine and the power of partnerships to help accelerate progress for patients we aim to continue building strategic partnerships like this one to drive medical progress for patients, innovation, and ultimately shareholder value.

研究人員正在評估5401名患有BRCA1或BRCA2基因突變的患者。這種候選疫苗可能有可能為攜帶這些突變的人預防乳癌。這項研究最近在《Today Show》上得到了重點報道，強調了DNA 醫學的潛力和合作夥伴關係的力量，以幫助加快患者的進步，我們的目標是繼續建立像這樣的戰略合作夥伴關係，以推動患者的醫療進步、創新和最終股東價值。

We also remain encouraged by the final data reported earlier this year from the study of INO-3112 in head neck cancer in combination with the PD-L1 checkpoint inhibitor. We are continuing discussions to find a potential PD-1 checkpoint partner to advance this promising candidate and believe there is significant opportunity to be explored for 3112 in combination with the proven PD-1 checkpoint inhibitor. On the infectious disease side, earlier this year, we announced positive data from a Phase 1 study for INO-4201 as the potential Ebola vaccine booster by continuing discussions with our partners for that program to determine next steps and evaluating potential funding opportunities.

我們也對今年稍早報告的 INO-3112 與 PD-L1 檢查點抑制劑聯合治療頭頸癌研究的最終數據感到鼓舞。我們正在繼續討論尋找潛在的 PD-1 檢查點合作夥伴來推進這一有前景的候選藥物，並相信 3112 與經過驗證的 PD-1 檢查點抑製劑聯合存在重大機會。在傳染病方面，今年早些時候，我們宣布了INO-4201 作為潛在伊波拉疫苗加強劑的一期研究的積極數據，並繼續與該計劃的合作夥伴進行討論，以確定後續步驟並評估潛在的融資機會。

We also have some exciting next-generation DNA medicines in early clinical development. For instance, our dMAbs and dLNPs and also candidates in preclinical development. We believe these next-generation candidates built on the strengths of our DNA medicines platform with significant potential advantages over other platforms. I'll now turn the call over to our CFO, Peter Kies for our third quarter 2023 financial summary. Peter?

我們還有一些令人興奮的下一代 DNA 藥物處於早期臨床開發階段。例如，我們的 dMAb 和 dLNP 以及臨床前開發的候選藥物。我們相信這些下一代候選藥物建立在我們 DNA 藥物平台的優勢之上，與其他平台相比具有顯著的潛在優勢。現在，我將把電話轉給我們的財務長 Peter Kies，以了解 2023 年第三季的財務摘要。彼得？

Thank you, Jacqui. Today, I'd like to provide an overview of Inovio's operational highlights and financial condition for the third quarter of 2023. As Jacqui noted and as required in today's economic environment, Inovio is committed to financial discipline as we advance our pipeline.

謝謝你，雅基。今天，我想概述 Inovio 2023 年第三季的營運亮點和財務狀況。正如 Jacqui 指出的那樣，根據當今經濟環境的要求，Inovio 在推進我們的管道時致力於遵守財務紀律。

To achieve our longer term goals, our strategy over the past 18 months has been to reprioritize our pipeline, reshape our organization, and scale our operational spend. As you can see from this slide, we have succeeded in bringing our operational spend down for both the third quarter and the nine-month period ended September 30, 2023, compared to the same period in 2022.

為了實現我們的長期目標，我們過去 18 個月的策略是重新調整我們的通路優先順序、重塑我們的組織並擴大我們的營運支出。正如您從這張幻燈片中看到的，與 2022 年同期相比，我們成功地降低了第三季和截至 2023 年 9 月 30 日的九個月期間的營運支出。

For the third quarter 2023, operational expenses dropped 20% to $35.9 million from $44.9 million compared to the same period in 2022. The third quarter included a one-time non-cash charge for goodwill impairment that totaled $10.5 million. Excluding that one-time charge, our operational expenses for the third quarter would have declined 43% from the same period or same quarter in 2022. For the first nine months of 2023, we cut our operating expenses nearly half dropping to $117.3 million from $221.8 million in the first nine months of 2022.

2023 年第三季度，營運費用從 2022 年同期的 4,490 萬美元下降 20% 至 3,590 萬美元。第三季度包括一次性非現金商譽減損費用，總額為 1,050 萬美元。如果不包括這項一次性費用，我們第三季的營運費用將比2022 年同期或同季下降43%。2023 年前9 個月，我們的營運費用削減了近一半，從221.8 美元降至1.173億美元。2022 年前 9 個月達到 100 萬美元。

Breaking down total operating expenses a bit more for the third quarter, our R&D expenses totaled $15.5 million in 2023 compared to $33.1 million for the same period in 2022. The decrease in R&D expenses was primarily the result of lower drug manufacturing clinical trial expenses and outside services related to INO-4800 and other COVID-19 studies and lower employee and consultant compensation, including stock-based compensation among other variances.

將第三季的總營運費用進一步細分，我們的研發費用在2023 年總計為1,550 萬美元，而2022 年同期為3,310 萬美元。研發費用的減少主要是由於藥品生產臨床試驗費用和外部費用減少的結果。與 INO-4800 和其他 COVID-19 研究相關的服務以及較低的員工和顧問薪酬，包括基於股票的薪酬以及其他差異。

G&A expenses for the third quarter 2023 were $9.9 million compared to $11.9 million for the same period in 2022. Revenues for the third quarter of 2023 were $388,000 compared to $9.2 million for the same period in 2022. Revenue reported for the 2022 third quarter was associated with a procurement contract with the US Department of Defense for Inovio's device and accessories to be used for delivery of INO-4800, which we have since discontinued. These factors combine to bring our net loss for the third quarter of 2023 to $33.9 million or $0.13 per share, basic and dilutive.

2023 年第三季的一般管理費用為990 萬美元，而2022 年同期為1,190 萬美元。2023 年第三季的營收為388,000 美元，而2022 年同期為920 萬美元。2022 年第三季報告的收入與與美國國防部簽訂了一份採購合同，購買 Inovio 的設備和配件，用於交付 INO-4800，但我們已停止生產該產品。這些因素結合在一起，使我們 2023 年第三季的淨虧損達到 3,390 萬美元，即每股基本虧損和攤薄虧損 0.13 美元。

Excluding previously mentioned one-time non-cash charge for goodwill impairment, our loss would have been $0.09 per share, basic and diluted. For the 2022 third quarter, our net loss of $37.8 million or $0.15 per share, basic and diluted. We finished the third quarter of 2023 with $167.5 million in cash, cash equivalents, and short-term investments compared to $253 million as of December 31, 2022.

不包括前面提到的一次性非現金商譽減損費用，我們的基本損失和稀釋損失將為每股 0.09 美元。 2022 年第三季度，我們的淨虧損為 3,780 萬美元，即每股淨虧損 0.15 美元（基本虧損和稀釋虧損）。截至 2023 年第三季度，我們的現金、現金等價物和短期投資為 1.675 億美元，截至 2022 年 12 月 31 日為 2.53 億美元。

Following feedback from the FDA on the accelerated approval pathway for INO-3107, we now estimate that our funds should support operations into second quarter of 2025. This projection includes a cash burn estimate of approximately $26 million for the fourth quarter of 2023. These projections do not include any funds that may be raised through our existing at-the-market program or other capital raise activities. 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 Jacqui.

根據 FDA 對 INO-3107 加速批准途徑的回饋，我們現在估計我們的資金應該支持到 2025 年第二季度的營運。該預測包括 2023 年第四季度約 2600 萬美元的現金消耗估計。這些預測不包括透過我們現有的市場計劃或其他籌資活動可能籌集的任何資金。謹此提醒，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。然後，我會將其轉回給 Jacqui。

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

謝謝，彼得。我現在想打開電話來回答您可能有的任何問題，或者接線員？

(Operator Instructions) Roger Song, Jefferies.

（操作員說明） Roger Song，Jefferies。

Great. Congrats for all the progress and thanks for taking the question. Maybe just focusing on the RRP program, the first question is related to the BLA filing and the Phase 3 confirmatory study design. Can you just let us know what is the outstanding items for the filing and the confirmatory study design? And any current guidance around the timing of the BLA filing and the potential approval? Thank you.

偉大的。恭喜您取得的所有進展，並感謝您提出問題。也許只關注 RRP 計劃，第一個問題與 BLA 備案和第 3 階段驗證性研究設計有關。您能否告訴我們，備案和驗證性研究設計有哪些突出的項目？目前有關於 BLA 提交時間和潛在批准的任何指導嗎？謝謝。

Thanks, Roger. It's nice to hear your voice. So as we mentioned during the call, the news on accelerated approval pathway is relatively new. We just heard in September. So over the past few weeks, we've really been working to accelerate our timelines. We've put together quite a detailed package to be considered by the FDA under the upcoming meeting. And I'll hand over to Mike to provide a few more details there. But what we're really hoping to achieve in that meeting is to get some alignment with the FDA as to some of the content that needs to go into that submission package as well as some further discussion on the design of the confirmatory study. Mike?

謝謝，羅傑。很高興聽到你的聲音。正如我們在電話會議中提到的，有關加速審批途徑的消息相對較新。我們九月才聽說。因此，在過去的幾周里，我們一直在努力加快進度。我們已經制定了相當詳細的一攬子計劃，供 FDA 在即將召開的會議上審議。我將請麥克提供更多詳細資訊。但我們真正希望在這次會議上實現的是就需要納入提交包的一些內容以及有關驗證性研究設計的進一步討論與 FDA 達成一致。麥克風？

Thank you, Jacqui. I think you hit some of the highlights. Obviously, since we heard the news in September, we've made tremendous progress as a team. We've really mapped out every single function and what we need to do to get to our BLA.

謝謝你，雅基。我認為你抓住了一些亮點。顯然，自從我們九月聽到這個消息以來，我們作為一個團隊已經取得了巨大的進步。我們確實已經規劃了每一個功能以及實現 BLA 所需要做的事情。

In terms of the input we need from the FDA, obviously, we have a strategy. We need to get the FDA to agree to that strategy. But we're pulling on significant data points that we've had. We've already gone through our PPQ strategy for 3100. We've used selector device in our Phase 3 program. We've had several interactions with the agency on what we need to do for the device.

顯然，就我們需要 FDA 提供的意見而言，我們有一個策略。我們需要讓 FDA 同意這項策略。但我們正在利用我們所擁有的重要數據點。我們已經完成了 3100 的 PPQ 策略。我們在第 3 階段計劃中使用了選擇器設備。我們已經與該機構就我們需要為該設備做的事情進行了多次互動。

We know, again, from a confirmatory study, what we want to propose, and we've had significant input of what we believe is going to be acceptable to the agency. And so we need alignment on that protocol as we do need to start that study prior to filing our BLA. But overall, based on all the interactions we've had on our platform and specifically around RRP, we're in a very good place. And now it's really just going through the process of aligning strategy with the agency so we can move rapidly forward.

我們再次從驗證性研究中知道了我們想要提出的建議，我們已經獲得了我們認為該機構可以接受的重要意見。因此，我們需要對該方案進行協調，因為我們確實需要在提交 BLA 之前開始研究。但總的來說，根據我們在平台上進行的所有互動，特別是圍繞 RRP 的互動，我們處於一個非常好的位置。現在，我們實際上只是在經歷與該機構協調策略的過程，這樣我們就可以快速前進。

Great, thanks. Maybe just a quick question around the commercial infrastructure with the current runway into second quarter of 2025, how should we think about the overall commercialization cost post approval for assuming the approval for RRP?

萬分感謝。也許只是一個圍繞商業基礎設施的簡單問題，目前的跑道到 2025 年第二季度，我們應該如何考慮批准 RRP 後的整體商業化成本？

Yes, that's a really great question, Roger. Before I ask Mark to jump in there, I think really this upcoming discussion with the agency will really help us be more definitive on the timelines. Mark can talk a bit about this in a bit more detail, but I think one of the encouraging things for us as a relatively small biotech company is that this is a rare disease.

是的，這是一個很好的問題，羅傑。在我請馬克介入之前，我認為即將與該機構進行的討論將真正幫助我們在時間表上更加明確。馬克可以更詳細地談論這一點，但我認為對於我們作為一家相對較小的生物技術公司來說，令人鼓舞的事情之一是這是一種罕見的疾病。

We believe that there are a reasonable number of core points for a company of our size to take on. We have in-house manufacturing for our device that we think can meet our device manufacturing needs. And we have well-established relationships with our drug manufacturing CMO to manufacture the drug. So, Mark, maybe you can talk a bit more about how we're thinking about going to market for 3107.

我們相信，對於我們這樣規模的公司來說，有合理數量的核心點可以承擔。我們擁有自己的設備製造工廠，我們認為這些設備可以滿足我們的設備製造需求。我們與藥品生產 CMO 建立了良好的關係來生產藥品。那麼，Mark，也許您可以多談談我們如何考慮將 3107 推向市場。

Thanks, Jacqui. Great questions. I think that Jacqui really hit the nail on the head when she was talking about this laryngology space and for RRP and being a perfect fit for Inovio. If we think about the [PhilTels] organization, we're thinking now that there are roughly between 300 and 400 laryngologists that are performing the majority of the RRP surgeries in the US. And we really think that a small specialty sales force can efficiently address the needs for both patients and physicians.

謝謝，雅基。很好的問題。我認為，當 Jacqui 談論喉科領域、RRP 以及與 Inovio 的完美契合時，她確實一語中的。如果我們考慮一下 [PhilTels] 組織，我們現在就會想到大約有 300 到 400 名喉科醫生在美國進行大部分 RRP 手術。我們確實認為，一支小型專業銷售團隊可以有效地滿足患者和醫生的需求。

But I think the other component speaks to the experience that we have in the organization in commercializing products. We're getting an early start. It's not just about the sales organization, but it's about everything you're doing behind that, from the perspective of your distribution strategy, the early conversations you need to have with payers and PBM, specialty pharmacy.

但我認為另一個組成部分說明了我們組織在產品商業化方面的經驗。我們很早就開始了。這不僅與銷售組織有關，還與您在背後所做的一切有關，從分銷策略的角度來看，您需要與付款人和 PBM、專業藥房進行早期對話。

So that's all work that's been started. And I think what is emerging is that we've identified the key workstreams. We've begun to identify the key partners that we need to have onboard. And I feel really good about where we are right now being able to leverage this accelerated approval.

這就是已經開始的所有工作。我認為我們已經確定了關鍵的工作流程。我們已經開始確定我們需要的關鍵合作夥伴。我對我們現在能夠利用這種加速批准的情況感到非常滿意。

Thanks, Mark and Roger, to answer your question about costs, we are planning to operate a lean and efficient model. So where it makes sense for us to do things in house, we'll do them in-house; where it makes sense to leverage other people's capabilities, such as a contract sales force and potentially defer expense there, we'll be doing that. So I think we'll be able to provide a bit more guidance in terms of our phasing of our cash runway over 2024 once we've had that discussion with the with the FDA.

謝謝馬克和羅傑回答你們關於成本的問題，我們計劃經營一個精益高效的模型。因此，如果我們認為在內部做事情有意義，我們就會在內部做；如果需要利用其他人的能力，例如合約銷售人員並可能推遲那裡的費用，我們就會這樣做。因此，我認為，一旦我們與 FDA 進行了討論，我們將能夠就 2024 年現金跑道的分階段提供更多指導。

Yeah, that makes sense. Thanks a lot for the comments. That's it from me.

是的，這是有道理的。非常感謝您的評論。這就是我說的。

(Operator Instructions) Yi Chen, H.C. Wainwright.

（操作員指示） Yi Chen, H.C.溫賴特。

Hi. Thank you for taking my questions. Could you tell us whether any patients in a clinical trial have been redosed with INL-3107? And in the real-world setting, commercially speaking, do you think laryngologists will have the flexibility of those choosing how often a particular patient should be dosed with 3107? Or that could be limited by payers to, let's say, just once every year?

你好。感謝您回答我的問題。您能否告訴我們臨床試驗中是否有患者重新接受了 INL-3107 治療？在現實世界中，從商業角度來說，您認為喉科醫生是否可以靈活地選擇特定患者服用 3107 的頻率？或者付款人可能會限制每年一次？

Well, I'll hand over to Mike, maybe for talking about initial clinical question on the completed Phase 1/2 trial. And then Mark, maybe you and Mike together can address the next question.

好吧，我會把時間交給 Mike，也許是為了談論已完成的 1/2 期試驗的初步臨床問題。然後馬克，也許你和麥克可以一起解決下一個問題。

So, I mean, starting off, obviously, one of the real benefits of the DNA medicines platform is there's no anti-vector response. And we believe redosing is capable. In fact, we know redosing is capable from many of our oncology programs. At present, we have not redosed any of the patients from the phase 1/2 study. But as we come to think about those patients, we obviously saw some patients with complete response. We saw a significant number of patients with a very good partial response with greater than 50% reduction in their surgeries.

所以，我的意思是，顯然，DNA 藥物平台的真正好處之一是沒有抗載體反應。我們相信重做是有能力的。事實上，我們知道我們的許多腫瘤學課程都可以進行重劑量治療。目前，我們還沒有對 1/2 期研究中的任何患者進行重新給藥。但當我們思考這些患者時，我們顯然看到一些患者獲得了完全緩解。我們看到大量患者獲得了非常好的部分緩解，手術次數減少了 50% 以上。

And then, unfortunately, there were a few patients who didn't show such great response. For me, I keep all those three buckets separate from my clinical strategy. But we certainly want to, in the future, examine how we can continue to build on the excellent clinical efficacy we've seen to date. But I would say, obviously, until that's in our label, it would all be off label. And so it would be down to the clinicians to decide what they want to do with their patients.

然後，不幸的是，有一些患者沒有表現出如此好的反應。對我來說，我將這三個部分與我的臨床策略分開。但我們當然希望在未來研究如何繼續鞏固我們迄今為止所看到的出色的臨床療效。但我想說，顯然，直到它進入我們的標籤之前，它都將是標籤外的。因此，臨床醫生應該決定他們想對病人做什麼。

Yeah. I think what I would add to that, Mike is, the question, will payers decide? I think that what I know is that we have a very strong value proposition for INO-3107. I think we can all look at the results to date from a clinical perspective and know that we have a real potential to address this unmet medical need, both from a patient perspective.

是的。我想我要補充的是，麥克，問題是付款人會決定嗎？我認為我所知道的是我們對 INO-3107 有非常強大的價值主張。我認為我們都可以從臨床角度看待迄今為止的結果，並知道我們有真正的潛力來解決這個未滿足的醫療需求，無論是從患者的角度來看。

It still unsettles me to know that some of these patients experience hundreds of surgeries over a lifetime. And that comes with significant cost burden and just how they go about living their daily lives. But the other point is that physicians aren't satisfied. These surgeons are used to treating and resolving an issue that their patient might have. And that's just not the case with RRP and hence the name recurrent respiratory papillomatosis. And I know from having a number of discussions with some of the key KOLs and physicians that are doing a large number of surgeries that they are really looking forward to having this option. And it's really our job, and it's the job we've already started to make sure that there's alignment with what the payers value INO-3107, and the fact that physicians are looking for a new option for treating RRP. So I'm feeling really good about where we are, but we'll have to get to the finish line.

知道其中一些患者一生經歷了數百次手術仍然讓我感到不安。這帶來了巨大的成本負擔以及他們的日常生活方式。但另一點是醫生並不滿意。這些外科醫生習慣於治療和解決患者可能遇到的問題。 RRP 的情況並非如此，因此被稱為複發性呼吸道乳頭狀瘤病。透過與一些進行大量手術的關鍵 KOL 和醫生的多次討論，我知道他們真的很期待有這個選擇。這確實是我們的工作，我們已經開始這項工作，以確保與付款人對 INO-3107 的評價一致，以及醫生正在尋找治療 RRP 的新選擇這一事實。所以我對我們現在的處境感覺非常好，但我們必須到達終點。

Will redosing be part of the Phase 3 trial?

重新服藥會成為第三階段試驗的一部分嗎？

We're still in discussions with the agency regarding that and haven't really put the details out there. But as I said, it's certainly something that we are thinking about.

我們仍在與該機構就此進行討論，但尚未真正公佈細節。但正如我所說，這肯定是我們正在考慮的事情。

Okay. Thank you.

好的。謝謝。

(Operator Instructions) There are no further questions at this time, please continue.

（操作員說明） 目前沒有其他問題，請繼續。

Thank you. The significant progress we have made in advancing INO-3107 over the past few months means that we are moving closer to providing a potentially life-changing, non-surgical treatment option to patients suffering from RRP. I remain incredibly grateful to the patients, patient advocates, trial investigators, and our dedicated team here at Inovio that has enabled us to achieve this. I'm confident that our experienced team is prepared for the next critical steps of development and potential commercialization for INO-3107. And thanks to the corporate strategy we've been implementing over the past year.

謝謝。過去幾個月，我們在推進 INO-3107 方面取得的重大進展意味著我們距離為 RRP 患者提供可能改變生活的非手術治療選擇又近了一步。我仍然非常感謝患者、患者倡導者、試驗研究者以及 Inovio 的敬業團隊，他們使我們能夠實現這一目標。我相信，我們經驗豐富的團隊已為 INO-3107 的下一個關鍵開發步驟和潛在商業化做好了準備。這要歸功於我們在過去一年中實施的企業策略。

I'm also confident that Inovio now has the key drivers in place for broader long-term success. We have a diversified pipeline focused on candidates with scientific and clinical promise, achievable pathways to market and strong commercial potential. We have our proprietary DNA medicines platform and technology, along with a history of strong partnerships to accelerate progress and innovation. And we have the benefits of an incredibly experienced team focused on financial discipline, operational excellence.

我還相信，Inovio 現在已具備實現更廣泛長期成功的關鍵驅動力。我們擁有多元化的管道，專注於具有科學和臨床前景、可實現的市場途徑和強大商業潛力的候選人。我們擁有專有的 DNA 藥物平台和技術，以及加速進步和創新的強大合作夥伴關係的歷史。我們擁有一支經驗豐富的團隊，專注於財務紀律和卓越營運。

I'm motivated by the patients who could someday benefit from the power of DNA medicine. There is much work to be done, but I speak for the entire Inovio team when I say that we are energized by what the future could hold for DNA medicine and patients around the world. With that, thank you again for your attention. Have a great evening, everyone.

我的動力來自於那些有朝一日可以從 DNA 醫學的力量中受益的患者。雖然還有很多工作要做，但當我說我們對 DNA 醫學和世界各地患者的未來充滿活力時，我代表整個 Inovio 團隊。在此，再次感謝您的關注。祝大家有個愉快的夜晚。

Thank you. Ladies and gentlemen, that does conclude our conference for today. Thank you all for participating. You may all disconnect.

謝謝。女士們、先生們，今天的會議到此結束。感謝大家的參與。你們都可以斷開連線。