Inovio Pharmaceuticals Inc (INO) 2022 Q4 法說會逐字稿

Good afternoon, and welcome to the Inovio Pharmaceuticals Fourth Quarter 2020 Financial Results Conference Call. (Operator Instructions) Please note, this event is being recorded.

下午好，歡迎參加 Inovio Pharmaceuticals 2020 年第四季度財務業績電話會議。 （操作員說明）請注意，正在記錄此事件。

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

我現在想將會議轉交給投資者關係經理 Thomas Hong。請繼續。

Good afternoon, and thank you for joining the INOVIO 2022 Fourth Quarter and Full Year Financial Results Conference Call. Joining me on today's call are Dr. Jacqui Shea, President and CEO; Dr. Michael Sumner, Chief Medical Officer; and Mr. Peter Kies, Chief Financial Officer. We also have other members of INOVIO's leadership here with us today who will be part of our Q&A session.

下午好，感謝您參加 INOVIO 2022 年第四季度和全年財務業績電話會議。與我一起參加今天電話會議的還有總裁兼首席執行官 Jacqui Shea 博士； Michael Sumner 博士，首席醫療官；首席財務官 Peter Kies 先生。 INOVIO 領導層的其他成員今天也和我們一起來到這裡，他們將參加我們的問答環節。

Today's call will review our corporate and financial information for the quarter and year ended December 31, 2022, as well as provide an update on our efforts to develop our DNA medicines platform. Following prepared remarks, we will conduct a question-and-answer segment.

今天的電話會議將審查我們截至 2022 年 12 月 31 日的季度和年度的公司和財務信息，並提供我們開發 DNA 藥物平台的最新進展。在準備好的評論之後，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.

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 的 DNA 藥物平台的商業計劃有關，其中包括臨床和監管發展以及臨床數據讀出的時間安排，以及資本資源和戰略事項。所有這些陳述都是基於管理層截至目前的信念和期望。

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存在重大差異。我們建議您參考我們不時向美國證券交易委員會提交的文件，這些文件在風險因素標題下確定了可能導致實際結果與公司口頭表達的結果以及今天下午的新聞中發表的聲明存在重大差異的重要因素發布。此電話會議正在進行網絡直播，可以在我們的網站 ir.INOVIO.com 上找到鏈接，電話會議結束後不久將提供重播。

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 的總裁兼首席執行官 Jacqui Shea 博士。

Thank you, Thomas. Good afternoon, and thank you to everyone for joining today's call. In the past year, INOVIO has taken measured and, at times, difficult steps to prioritize our pipeline to focus on our programs with the highest probability of clinical and regulatory success and strongest commercial potential. Guided by our commitment to operational excellence and financial discipline, we are positioning INOVIO to best advance our key clinical programs and realize the potential of DNA medicines for patients.

謝謝你，托馬斯。下午好，感謝大家參加今天的電話會議。在過去的一年裡，INOVIO 採取了慎重的、有時是艱難的步驟來確定我們管道的優先順序，以專注於我們的項目，這些項目在臨床和監管方面取得成功的可能性最大，商業潛力最大。在我們對卓越運營和財務紀律的承諾的指導下，我們將 INOVIO 定位為最好地推進我們的關鍵臨床項目並實現 DNA 藥物對患者的潛力。

In our press release today, we announced the top line results from our REVEAL2 trial of VGX-3100. Later in the call, our Chief Medical Officer, Dr. Mike Sumner, will provide a detailed summary of our clinical programs, but I'd like to take this opportunity to highlight some key points about the REVEAL2 trial as well as our work on INO-3107 as a potential treatment for recurrent respiratory papillomatosis, or RRP, both of which are HPV-related diseases.

在今天的新聞稿中，我們公佈了 VGX-3100 的 REVEAL2 試驗的主要結果。稍後在電話會議中，我們的首席醫療官 Mike Sumner 博士將提供我們臨床計劃的詳細摘要，但我想藉此機會強調有關 REVEAL2 試驗以及我們在 INO 上的工作的一些要點-3107 作為複發性呼吸道乳頭狀瘤病或 RRP 的潛在治療方法，這兩種疾病都是 HPV 相關疾病。

As you may recall, in April last year, we changed the primary end point of REVEAL2 from an all-participants population to an investigational biomarker-selected population. We made this decision based on our analysis of data from REVEAL1 from which we have defined an investigational biomarker signature that may have the potential to identify those women more likely to respond to treatment with VGX-3100.

您可能還記得，去年 4 月，我們將 REVEAL2 的主要終點從所有參與者人群更改為研究性生物標誌物選擇人群。我們根據對 REVEAL1 數據的分析做出了這一決定，我們從中定義了一個研究性生物標誌物特徵，該特徵可能有可能識別出那些更有可能對 VGX-3100 治療產生反應的女性。

In REVEAL2, VGX-3100 did not achieve statistical significance in the primary biomarker-selected population for the end point of lesion regression and viral clearance. However, VGX-3100 did achieve statistical significance in the all-participants population, the original primary population for the trial for the end point of lesion regression and viral clearance.

在 REVEAL2 中，VGX-3100 在主要生物標誌物選擇的人群中未達到病變消退和病毒清除終點的統計學顯著性。然而，VGX-3100 確實在所有參與者人群中取得了統計顯著性，即病變消退和病毒清除終點試驗的原始主要人群。

Furthermore, the REVEAL2 all-participants data and the combined data across REVEAL1 and REVEAL2 trials, build upon the considerable data package that we've now obtained over multiple clinical trials that indicate DNA medicines are potentially able to clear the HPV virus and regress HPV-related lesions. It also strengthens our confidence in our other HPV-related programs, including INO-3107 for RRP where we recently reported encouraging data from the first and second cohorts from a Phase I/II trial. RRP is a truly devastating disease that can be overwhelming in patients' lives. And we believe INO-3107 has the potential to help alleviate this burden and improve the quality of life for those suffering from this terrible disease. We are focused on advancing INO-3107 to the next stage of development, and I look forward to sharing updates on our progress with you in the coming months.

此外，REVEAL2 所有參與者的數據以及 REVEAL1 和 REVEAL2 試驗的綜合數據，建立在我們現在通過多項臨床試驗獲得的大量數據包的基礎上，這些數據包表明 DNA 藥物有可能清除 HPV 病毒並使 HPV-相關病變。它還增強了我們對我們其他 HPV 相關項目的信心，包括用於 RRP 的 INO-3107，我們最近報告了來自 I / II 期試驗的第一和第二隊列的令人鼓舞的數據。 RRP 是一種真正具有破壞性的疾病，可以壓倒患者的生活。我們相信 INO-3107 有潛力幫助減輕這種負擔並改善患有這種可怕疾病的人們的生活質量。我們專注於將 INO-3107 推進到下一階段的開發，我期待在未來幾個月與您分享我們的最新進展。

Moving on to our infectious disease portfolio. Last month, we announced positive results from a Phase Ib clinical trial evaluating INO-4201 as a booster vaccine candidate in healthy adult participants who have previously received a single injection of Ervebo, an FDA-approved vaccine for Ebola. We believe this data supports our position that DNA medicines could be an important part of global medical countermeasures against infectious diseases, either as primary vaccines or as boosters to existing vaccines. Infectious diseases like Ebola, remain an ever-present threat globally. We are currently in discussions with our collaborators and also potential partners regarding the next development steps for INO-4201.

繼續我們的傳染病產品組合。上個月，我們宣布了一項 Ib 期臨床試驗的積極結果，該試驗評估了 INO-4201 作為健康成人參與者的加強疫苗候選者，這些參與者之前曾接受過 Ervebo 的單次注射，Ervebo 是 FDA 批准的埃博拉疫苗。我們相信這些數據支持我們的立場，即 DNA 藥物可能成為全球針對傳染病的醫學對策的重要組成部分，無論是作為主要疫苗還是作為現有疫苗的助推器。像埃博拉這樣的傳染病在全球範圍內仍然是一個永遠存在的威脅。我們目前正在與我們的合作者以及潛在合作夥伴討論 INO-4201 的下一步開發步驟。

In addition to the progress on the clinical front, we have been working to strengthen our financial position. Peter will provide the details, but our emphasis on pipeline prioritization, operational excellence and financial discipline has allowed us to reduce our cash burn substantially since last year. Given these efforts, our cash runway is expected to take us into the first quarter of 2025. Financial prudence will continue to be an area of high importance for INOVIO and underpin our decision-making process going forward.

除了在臨床方面取得進展外，我們一直在努力加強我們的財務狀況。 Peter 將提供詳細信息，但我們對管道優先級、卓越運營和財務紀律的重視使我們自去年以來大幅減少了現金消耗。鑑於這些努力，我們的現金跑道預計將帶我們進入 2025 年第一季度。財務審慎將繼續成為 INOVIO 的一個高度重要的領域，並支撐我們未來的決策過程。

With that, I'd like to turn the call over to Mike to provide a more detailed update on our clinical pipeline and recent highlights. Mike?

有了這個，我想把電話轉給邁克，提供關於我們臨床管道和最近亮點的更詳細的更新。麥克風？

Thank you very much, Jacqui, and greetings, everyone. I'd like to start today by talking about VGX-3100 and sharing some more detailed insights on the REVEAL2 results we announced today in our financial press release.

非常感謝你，Jacqui，問候大家。今天，我想先談談 VGX-3100，並就我們今天在財經新聞稿中宣布的 REVEAL2 結果分享一些更詳細的見解。

Our Phase III program for VGX-3100 includes REVEAL1 and REVEAL2, 2 trials evaluating the efficacy, safety, tolerability and immunogenicity of VGX-3100 to treat HPV-16/18-associated cervical high-grade squamous intraepithelial lesions, or HSIL. Both trials included a 3-dose treatment regimen and used regression of cervical lesions along with clearance of the virus as the primary end point.

我們的 VGX-3100 III 期計劃包括 REVEAL1 和 REVEAL2，這兩項試驗評估了 VGX-3100 治療 HPV-16/18 相關宮頸高度鱗狀上皮內病變或 HSIL 的療效、安全性、耐受性和免疫原性。這兩項試驗都包括 3 劑治療方案，並使用宮頸病變的消退和病毒清除作為主要終點。

In REVEAL1, the end point was evaluated against all participants in the clinical trial. But in the second quarter of 2022, we amended the REVEAL2 trial to focus on investigational biomarker-selected population. As Jacqui described, we made this decision based on our analysis of data from REVEAL1, in which we had defined an investigational biomarker signature that may have the potential to identify those women more likely to respond to treatment with VGX-3100. Due to that amendment, we publicly announced that REVEAL2 was no longer deemed to be a pivotal trial and would not lead to a biologics license application for a biomarker-selected population since the U.S. Food and Drug Administration had indicated that an additional trial or trials would be required.

在 REVEAL1 中，終點是針對臨床試驗的所有參與者進行評估的。但在 2022 年第二季度，我們修改了 REVEAL2 試驗，將重點放在研究性生物標誌物選擇的人群上。正如 Jacqui 所描述的，我們根據對 REVEAL1 數據的分析做出了這一決定，我們在其中定義了一個研究性生物標誌物特徵，該特徵可能有可能識別出那些更有可能對 VGX-3100 治療產生反應的女性。由於該修正案，我們公開宣布 REVEAL2 不再被視為關鍵試驗，並且不會導致針對生物標誌物選擇人群的生物製品許可申請，因為美國食品和藥物管理局表示額外的試驗或試驗將需要。

As the next slide shows, the results from REVEAL1 in the all-participants intent-to-treat population did not achieve statistical significance. However, a modified intent-to-treat population did indeed reach significance. Following the change of primary end point in REVEAL2, the result in the biomarker population was also not statistically significant. The percentage of participants meeting the primary end point was 28.6% or 6 out of the 21 participants in the treatment group versus 0 out of the 4 in the placebo group.

正如下一張幻燈片所示，REVEAL1 在所有參與者的意向治療人群中的結果沒有達到統計學意義。然而，修改後的意向治療人群確實達到了顯著性。在 REVEAL2 中主要終點發生變化後，生物標誌物群體的結果也沒有統計學意義。達到主要終點的參與者百分比為 28.6%，即治療組 21 名參與者中有 6 人，而安慰劑組 4 人中有 0 人。

The next slide shows the 2 studies and 2 populations side by side in more detail. We just discussed the REVEAL2 biomarker results that you can see in the bottom right quadrant. However, the all-participants group in REVEAL2, shown in green in the top right quadrant, did achieve statistical significance. The percentage of patients meeting the end point was 27.6% in the treatment group versus 8.7% in the placebo group. In addition, the treatment effect we saw was higher than observed in REVEAL1. While not shown on the slide, we also achieved statistical significance in the all-participants population of REVEAL2 for viral clearance, with 37.3% in the treatment group achieving viral clearance versus 8.7% in the placebo group. Given the importance of viral clearance in removing the underlying cause of the HPV-related diseases, this data may have positive implications for our other HPV-related programs.

下一張幻燈片更詳細地並排顯示了 2 項研究和 2 個人群。我們剛剛討論了您可以在右下象限中看到的 REVEAL2 生物標誌物結果。然而，在右上象限以綠色顯示的 REVEAL2 中的所有參與者組確實達到了統計顯著性。治療組達到終點的患者百分比為 27.6%，而安慰劑組為 8.7%。此外，我們看到的治療效果高於在 REVEAL1 中觀察到的效果。雖然未在幻燈片上顯示，但我們還在 REVEAL2 的所有參與者人群中實現了病毒清除的統計顯著性，治療組中有 37.3% 的人實現了病毒清除，而安慰劑組中有 8.7% 的人實現了病毒清除。鑑於病毒清除對於消除 HPV 相關疾病根本原因的重要性，該數據可能對我們其他 HPV 相關項目產生積極影響。

Next, we can look at the integrated results from both REVEAL1 and 2. Since these trials utilize the same end point, we performed an ad hoc integrated efficacy analysis of the results. This analysis showed that we achieved statistical significance in both the biomarker and in the all-participants populations. For the combined biomarker population, which consisted of 92 participants, 68 of which were in the treatment group and 24 in the placebo group, the percentage of participants meeting the end point was 54.4% in the treatment group versus 12.5% in the placebo group. For the combined all-participants population of 404 participants, 272 of which were in the treatment group and 132 in the placebo group, the percentage of participants meeting the end point was 25% in the treatment group versus 9.8% in the placebo group.

接下來，我們可以查看 REVEAL1 和 2 的綜合結果。由於這些試驗使用相同的終點，我們對結果進行了臨時綜合功效分析。該分析表明，我們在生物標誌物和所有參與者群體中都取得了統計學意義。對於由 92 名參與者組成的組合生物標誌物人群，其中治療組 68 名，安慰劑組 24 名，達到終點的參與者百分比在治療組中為 54.4%，在安慰劑組中為 12.5%。對於 404 名參與者的合併所有參與者群體，其中 272 名在治療組，132 名在安慰劑組，達到終點的參與者百分比在治療組中為 25%，在安慰劑組中為 9.8%。

With respect to safety in the REVEAL2 trial, there were no treatment-related serious adverse events, and most adverse events were considered to be mild to moderate. These results were consistent with what was observed in REVEAL1.

關於 REVEAL2 試驗的安全性，沒有與治療相關的嚴重不良事件，大多數不良事件被認為是輕度至中度。這些結果與在 REVEAL1 中觀察到的一致。

INOVIO will continue to evaluate the results to determine the path forward for VGX-3100 in cervical HSIL. And this combined data set will be supportive in future regulatory interactions. We also plan to submit the data for publication in a peer-reviewed journal later this year.

INOVIO 將繼續評估結果，以確定 VGX-3100 在宮頸 HSIL 中的前進道路。這個組合數據集將支持未來的監管互動。我們還計劃在今年晚些時候提交數據，以便在同行評審的期刊上發表。

While disappointed that we did not meet the primary end point for REVEAL2 in the biomarker population, I am encouraged by the data as it further indicates that DNA medicines may be particularly well suited to treat HPV-related diseases. These results also give us additional confidence as we advance INO-3107 as candidate for the treatment of RRP into the next stage of development, which brings me to the recently announced data for INO-3107. As a reminder, INO-3107 is a DNA immunotherapy composed of 2 plasmids, one encoding for HPV 6 and 11, E6 and E7; and the second INO-9112, our plasmid encoding for human interleukin 12 as an adjuvant to boost the immune response. This DNA medicine candidate was evaluated in an open-label multicenter trial to assess its safety, tolerability, immunogenicity and efficacy in patients with HPV 6 and/or HPV 11-associated RRP.

雖然對我們在生物標誌物人群中未達到 REVEAL2 的主要終點感到失望，但我對這些數據感到鼓舞，因為它進一步表明 DNA 藥物可能特別適合治療 HPV 相關疾病。隨著我們將 INO-3107 作為治療 RRP 的候選藥物推進到下一開發階段，這些結果也給了我們額外的信心，這讓我想到了最近公佈的 INO-3107 數據。提醒一下，INO-3107 是一種由 2 個質粒組成的 DNA 免疫療法，一個編碼 HPV 6 和 11，E6 和 E7；第二個 INO-9112，我們編碼人白細胞介素 12 的質粒，作為增強免疫反應的佐劑。該 DNA 候選藥物在一項開放標籤多中心試驗中進行了評估，以評估其在 HPV 6 和/或 HPV 11 相關 RRP 患者中的安全性、耐受性、免疫原性和有效性。

There were 2 cohorts for this trial. Enrollment into the trial required a minimum of 2 surgeries in the year prior to treatment. In both cohorts, patients received 4 doses of INO-3107 on day 0 and weeks 3, 6 and 9. Surgery was performed once in the 2 weeks prior to the first dose in order to establish a disease baseline, but any surgery performed following day 0, including during the dosing window, was counted against efficacy.

該試驗有 2 個隊列。參加試驗需要在治療前一年至少進行 2 次手術。在兩個隊列中，患者在第 0 天和第 3、6 和 9 週接受了 4 劑 INO-3107。在第一次給藥前的 2 週內進行了一次手術以建立疾病基線，但第二天進行的任何手術0，包括在給藥窗口期間，被計入療效。

Last month, we reported positive preliminary results from the second cohort of 11 patients who were administered INO-3107 using the exploratory side port needle. The data from the second cohort achieved statistical significance based on the clinical end point of a reduction in the number of surgical interventions, echoing data from the first cohort announced in October of 2022. In particular, in the second cohort, we saw a median decrease of 3 surgical interventions, 10 of the 11 patients or 91% saw a reduction in surgical interventions in the year following treatment. Of those 10 patients, 4 required no surgical intervention during the 52-week trial period. In the year prior to treatment, these 11 patients had between 2 and 8 surgical interventions with a median of 5.

上個月，我們報告了第二組 11 名患者的積極初步結果，這些患者使用探查側端口針頭給予 INO-3107。基於手術干預次數減少的臨床終點，第二組的數據達到了統計學顯著性，與 2022 年 10 月宣布的第一組的數據相呼應。特別是，在第二組中，我們看到中位數下降在 3 次手術干預中，11 名患者中有 10 名或 91% 的患者在治療後的一年中手術干預有所減少。在這 10 名患者中，有 4 名在 52 週的試驗期間不需要手術干預。在治療前一年，這 11 名患者接受了 2 至 8 次手術干預，中位數為 5 次。

Treatment-induced cellular responses against both HPV 6 and HPV 11, inducing both activated CD4 and activated lytic CD8 T cells. T cell responses were also observed at week 52, which was 43 weeks after final treatment with INO-3107, indicating a persistent cellular memory response. As we mentioned previously, we believe this memory response could be a key factor in the treatment of chronic viral diseases such as RRP.

治療誘導的針對 HPV 6 和 HPV 11 的細胞反應，誘導活化的 CD4 和活化的裂解性 CD8 T 細胞。在第 52 周也觀察到 T 細胞反應，即最終用 INO-3107 治療後 43 週，表明持續的細胞記憶反應。正如我們之前提到的，我們相信這種記憶反應可能是治療 RRP 等慢性病毒性疾病的關鍵因素。

As we have seen with our other DNA medicines, INO-3107 was well tolerated in both the first and second cohorts, with all participants completing the treatment course. Treatment-emergent adverse events observed in the trial were generally low grade, with injection site pain and fatigue being the most commonly reported AEs.

正如我們在其他 DNA 藥物中看到的那樣，INO-3107 在第一組和第二組中的耐受性都很好，所有參與者都完成了治療過程。在試驗中觀察到的治療中出現的不良事件通常是低級別的，注射部位疼痛和疲勞是最常報告的不良事件。

When the data from both cohorts is combined, it shows that 81% or 26 of the 32 participants saw a reduction in the number of surgical interventions compared to the previous year. We found these results incredibly important not just because they show the potential of our platform but, more importantly, because of the potential impact INO-3107 can have on patients suffering from RRP. For instance, the 2 photos on this slide show the change in the airway of one of the patients in our trial from before and after treatment. This patient had required frequent surgeries in the year prior to the trial. But as you can see on the right, there was marked improvement in the disease, which meant, from a clinical management perspective, that this patient required no surgeries following treatment.

將兩個隊列的數據結合起來後，它表明與前一年相比，32 名參與者中有 81% 或 26 人的手術干預次數有所減少。我們發現這些結果非常重要，不僅因為它們展示了我們平台的潛力，而且更重要的是，因為 INO-3107 可能對 RRP 患者產生潛在影響。例如，這張幻燈片上的兩張照片顯示了我們試驗中一名患者治療前後氣道的變化。該患者在試驗前一年需要頻繁手術。但是正如您在右側看到的那樣，疾病有了明顯改善，這意味著從臨床管理的角度來看，該患者在治療後無需手術。

In this next slide, you can see the impact of INO-3107 on a patient with much more significant disease. The improvement here is tremendous. And while some residual disease is visible on the right side of the airway, this patient did not need any surgery after day 0 through the completion of the 52-week trial.

在下一張幻燈片中，您可以看到 INO-3107 對患有更嚴重疾病的患者的影響。這裡的改進是巨大的。雖然在右側氣道上可以看到一些殘留病灶，但該患者在第 0 天之後到 52 週試驗結束時不需要進行任何手術。

We have heard from patients and investigators that any reduction in surgery, even 1 less surgery would be life-changing for patients who often have to schedule their entire lives around surgical procedures to control their disease. Our Phase I/II results are an indication of the positive impact INO-3107 could potentially have for the RRP community. We are currently in discussions with the regulatory agencies to discuss the next steps for this program and determine the most expeditious path to bring the potential benefits of this treatment to RRP patients in need. We continue to have discussions with KOLs in U.S. and Europe as we plan to advance to the next clinical development stage with the goal of recruiting globally for the next trial.

我們從患者和研究人員那裡聽說，任何手術的減少，即使是少 1 次手術都會改變患者的生活，因為他們經常不得不圍繞手術程序來安排他們的整個生活來控制他們的疾病。我們的 I/II 期結果表明 INO-3107 可能對 RRP 社區產生積極影響。我們目前正在與監管機構討論該計劃的後續步驟，並確定將這種治療的潛在益處帶給有需要的 RRP 患者的最快捷途徑。我們繼續與美國和歐洲的 KOL 進行討論，因為我們計劃推進到下一個臨床開發階段，目標是在全球範圍內招募下一個試驗。

We are also excited to be presenting our Phase I/II trial data at the American Broncho-Esophageal Association (sic) [American Broncho-Esophagological Association] at COSM in May of this year. We look forward to providing additional details about our data at this important conference.

我們也很高興今年 5 月在 COSM 的美國支氣管食管協會（原文如此）[美國支氣管食管協會] 上展示我們的 I/II 期試驗數據。我們期待在這次重要會議上提供有關我們數據的更多詳細信息。

Now I'd like to turn to updates on a few other product candidates mentioned in today's press release.

現在我想談談今天新聞稿中提到的其他幾個候選產品的更新。

INO-3112 is our candidate for the treatment of HPV-related cancers. As you may recall, the asset was returned to us in 2021 from AstraZeneca. Updated results have recently been published in clinical cancer research which included an improved overall response rate, or ORR, from a Phase Ib/IIa trial evaluating the safety and tolerability, antitumor activity and immunogenicity of INO-3112 when used in combination with durvalumab, a PD-L1 checkpoint inhibitor. The ORR was updated from 22.2% to 27.6%, which meant the number of both complete responses and partial responses increased from 3 to 4. We believe the results from our HPV program to date supports the reevaluation of INO-3112. Therefore, we are currently evaluating the next development steps and also potential collaborators to move INO-3112 forward.

INO-3112 是我們治療 HPV 相關癌症的候選藥物。您可能還記得，該資產於 2021 年從阿斯利康歸還給我們。最新結果最近發表在臨床癌症研究中，其中包括 Ib/IIa 期試驗的總體緩解率或 ORR 提高，該試驗評估了 INO-3112 與 durvalumab 聯合使用時的安全性和耐受性、抗腫瘤活性和免疫原性， PD-L1 檢查點抑製劑。 ORR 從 22.2% 更新為 27.6%，這意味著完全緩解和部分緩解的數量從 3 增加到 4。我們相信我們的 HPV 項目迄今為止的結果支持對 INO-3112 的重新評估。因此，我們目前正在評估下一步的開發步驟以及潛在的合作者，以推動 INO-3112 向前發展。

Turning to INO-5401. Last year at ASCO, we announced additional overall survival data from our trial evaluating INO-5401 in combination with the PD-1 inhibitor, Libtayo. We are in discussions with Regeneron regarding the next steps for this program. Given the tolerability and immunogenicity profile when combined with the survival data, we believe this asset should continue to be investigated and we plan to provide additional updates in the coming months.

轉向 INO-5401。去年在 ASCO 上，我們公佈了我們評估 INO-5401 與 PD-1 抑製劑 Libtayo 聯合使用的試驗的額外總體生存數據。我們正在與 Regeneron 討論該計劃的後續步驟。考慮到與生存數據相結合的耐受性和免疫原性概況，我們認為應該繼續研究該資產，我們計劃在未來幾個月提供更多更新。

On the infectious disease front, we also announced positive results from our early phase clinical trial evaluating INO-4201 as a booster vaccine candidate in healthy adult participants who had previously received a single injection of Ervebo, the only FDA-approved vaccine for Ebola.

在傳染病方面，我們還宣布了早期臨床試驗的積極結果，該試驗評估了 INO-4201 作為健康成人參與者的加強疫苗候選者，這些參與者之前接受過單次注射 Ervebo，這是 FDA 批准的唯一埃博拉疫苗。

As you heard from Jacqui earlier, we believe DNA medicines have an important role to play as part of global medical countermeasures against infectious diseases. We are currently in discussions with collaborators and potential partners, and we'll seek regulatory input regarding what next steps we need to take to move this product forward. We will hopefully be able to provide a further update in the second half of this year.

正如您之前從 Jacqui 那裡聽到的那樣，我們相信 DNA 藥物作為全球傳染病醫學對策的一部分可以發揮重要作用。我們目前正在與合作者和潛在合作夥伴進行討論，我們將就我們需要採取哪些後續步驟來推動該產品向前發展徵求監管意見。我們希望能夠在今年下半年提供進一步的更新。

As you can see, we've been busy, and we have a lot of exciting work ahead. We believe our DNA medicines are well suited as therapeutics for chronic viral conditions. Attributes of DNA medicines such as durable T cell responses, a well-tolerated profile, ability to readminister and the lack of antivector response could play an important role in the treatment for HPV-related diseases. We are truly excited about taking our pipeline to the next stage of development.

如您所見，我們一直很忙，而且我們還有很多激動人心的工作要做。我們相信我們的 DNA 藥物非常適合作為慢性病毒性疾病的治療藥物。 DNA 藥物的屬性，如持久的 T 細胞反應、良好的耐受性、重新給藥的能力和缺乏抗病毒反應，可能在 HPV 相關疾病的治療中發揮重要作用。我們真的很高興將我們的管道帶入下一階段的開發。

I'll now turn the call over to our CFO, Peter Kies, for our 2022 fourth quarter and full year financial summary. Peter?

我現在將電話轉給我們的首席財務官彼得凱斯，了解我們 2022 年第四季度和全年的財務摘要。彼得？

Thank you, Michael. We finished the fourth quarter of 2022 with $253 million in cash, cash equivalents and short-term investments compared to $401.3 million as of December 31, 2021. As of December 31, 2022, INOVIO had 253.1 million common shares outstanding and 271 million common shares outstanding on a fully diluted basis.

謝謝你，邁克爾。截至 2022 年第四季度，我們的現金、現金等價物和短期投資為 2.53 億美元，而截至 2021 年 12 月 31 日為 4.013 億美元。截至 2022 年 12 月 31 日，INOVIO 擁有 2.531 億股已發行普通股和 2.71 億股普通股在完全稀釋的基礎上表現出色。

Our total revenue was $125,000 and $10.3 million for the quarter and year ended December 31, 2022, compared to $839,000 and $1.8 million for the same period in 2021, respectively. The year-over-year increase in revenue resulted from the fulfillment of obligations under our contract with the U.S. Department of Defense.

截至 2022 年 12 月 31 日止季度和年度，我們的總收入分別為 125,000 美元和 1,030 萬美元，而 2021 年同期分別為 839,000 美元和 180 萬美元。收入的同比增長是由於履行了我們與美國國防部簽訂的合同規定的義務。

Total operating expenses were $56.1 million and $277.8 million for the quarter and year ended December 31, 2022, compared to $106.3 million and $303 million for the same period in 2021.

截至 2022 年 12 月 31 日的季度和年度，總運營費用分別為 5610 萬美元和 2.778 億美元，而 2021 年同期為 1.063 億美元和 3.03 億美元。

Our net loss for the quarter and year ended December 31, 2022, was $54.5 million or $0.22 per share basic and dilutive, and $279.8 million or $1.17 per share basic and dilutive, respectively, compared to a net loss of $106.9 million or $0.50 per share basic and dilutive, and $303.7 million or $1.45 per share basic and dilutive for the quarter and year ended December 31, 2021.

我們截至 2022 年 12 月 31 日的季度和年度的淨虧損分別為 5450 萬美元或每股 0.22 美元基本和稀釋性，以及 2.798 億美元或每股 1.17 美元基本和稀釋性，而淨虧損為 1.069 億美元或每股 0.50 美元基本和稀釋性，以及截至 2021 年 12 月 31 日的季度和年度基本和稀釋性 3.037 億美元或每股 1.45 美元。

Research and development expenses for the quarter and year-end December 31, 2022, were $42.1 million and $187.7 million compared to $92.3 million and $249.2 million, respectively, for the same period in 2021. The year-over-year decrease in R&D expenses was primarily related to lower drug manufacturing, outside services and clinical expenses related to INO-4800 and VGX-3100 and also nonrecurring expenses related to the acquisition and installation of manufacturing equipment for INO-4800 during 2021 as well as lower engineering services and expenses related to our CELLECTRA 3PSP device array automation project. These decreases were offset by $29.2 million, lower contra-research and development expenses recorded from grant agreements.

截至 2022 年 12 月 31 日的季度和年度研發費用分別為 4210 萬美元和 1.877 億美元，而 2021 年同期分別為 9230 萬美元和 2.492 億美元。研發費用同比下降主要與減少與 INO-4800 和 VGX-3100 相關的藥物製造、外部服務和臨床費用以及與 2021 年為 INO-4800 購買和安裝製造設備相關的非經常性費用以及與以下相關的工程服務和費用減少有關我們的 CELLECTRA 3PSP 設備陣列自動化項目。這些減少被 2920 萬美元所抵消，這是從贈款協議中記錄的較低的對比研究和開發費用。

General and administrative expenses were $14 million and $90.2 million for the quarter and year ended December 31, 2022 versus $14 million and $53.8 million, respectively, for the same periods in 2021. The year-over-year increase in G&A expenses was primarily due to a $14 million noncash expense related to the settlement of INOVIO's securities class action litigation, including issuance of common stock as part of the settlement and other related litigation costs as well as $6.9 million in onetime severance expenses.

截至 2022 年 12 月 31 日的季度和年度，一般和行政費用分別為 1,400 萬美元和 9,020 萬美元，而 2021 年同期分別為 1,400 萬美元和 5,380 萬美元。G&A 費用的同比增長主要是由於與 INOVIO 證券集體訴訟和解相關的 1,400 萬美元非現金費用，包括作為和解的一部分發行普通股和其他相關訴訟費用，以及 690 萬美元的一次性遣散費。

Looking forward, our projected cash runway into first quarter 2025 includes a cash burn estimate of approximately $32 million for the first quarter of 2023. These projections do not include any funds that may be raised through our existing at-the-market program or other capital-raising activities.

展望未來，我們預計到 2025 年第一季度的現金跑道包括 2023 年第一季度的現金消耗估計約為 3200 萬美元。這些預測不包括可能通過我們現有的上市計劃或其他資本籌集的任何資金-籌款活動。

As a reminder, you can find our full financial statements in this afternoon's press release as well as in our Form 10-K filed with the SEC.

提醒一下，您可以在今天下午的新聞稿以及我們向美國證券交易委員會提交的 10-K 表格中找到我們的完整財務報表。

And with that, I'll turn it back to Jacqui.

有了這個，我會把它轉回 Jacqui。

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

謝謝，彼得。我現在想打開電話，回答您可能有的任何問題。操作員？

(Operator Instructions) Our first question today comes from Hartaj Singh with Oppenheimer.

（操作員說明）我們今天的第一個問題來自 Hartaj Singh 和 Oppenheimer。

A couple of questions, just quick ones. One is you had mentioned that you had learned a lot from the trials, REVEAL1 and REVEAL2, and the biomarker-selected patient population. And I imagine you're learning more going forward as you look at that data. Can you just help us understand how that helps you in the RRP trial, other trials that you're looking at with other projects? That's number one, how it's going to help you with all-comers and patient population? And then I just got a quick follow-up after.

幾個問題，只是快速的問題。一是你提到你從試驗 REVEAL1 和 REVEAL2 以及生物標誌物選擇的患者群體中學到了很多東西。我想你在查看這些數據時會學到更多。您能否幫助我們了解這如何幫助您進行 RRP 試驗，以及您正在與其他項目一起進行的其他試驗？這是第一，它將如何幫助您應對所有來訪者和患者群體？然後我得到了一個快速的跟進。

Thanks, Hartaj, nice to hear from you. So I'll kick off and sort of provide some top-level comments, and then I'm going to hand over to Mike to comment in more detail.

謝謝，Hartaj，很高興收到你的來信。因此，我將開始並提供一些頂級評論，然後我將交給 Mike 進行更詳細的評論。

So I think the really encouraging thing that we've seen from REVEAL1 and REVEAL2 and from the earlier Phase II trial for VGX-3100 and that we've also seen across the anal indication for VGX-3100 and now with RRP is our ability really to be able to see viral clearance and lesion regression. And I think that's a common factor that we're seeing across all of those different indications. And whilst we did not reach statistical significance in the biomarker-selected population, we did reach statistical significance against tissue regression and viral clearance in the all-comers population in REVEAL2. And I think this is really important data. And I think it really strengthens our belief and our conviction that DNA medicines are really particularly well suited to addressing HPV-related diseases.

所以我認為真正令人鼓舞的事情是我們從 REVEAL1 和 REVEAL2 以及早期的 VGX-3100 II 期試驗中看到的，我們也看到了 VGX-3100 的肛門指徵和現在的 RRP 是我們的能力真的能夠看到病毒清除和病變消退。我認為這是我們在所有這些不同適應症中看到的一個共同因素。雖然我們沒有在生物標誌物選擇的人群中達到統計顯著性，但我們確實在 REVEAL2 的所有參與者人群中達到了組織消退和病毒清除的統計顯著性。我認為這是非常重要的數據。我認為這確實加強了我們的信念和信念，即 DNA 藥物確實特別適合解決 HPV 相關疾病。

And with that, I'll hand it over to Mike to make some more specific comments. Mike?

然後，我將把它交給邁克，讓他發表一些更具體的意見。麥克風？

Thank you, Jacqui. And nice to speak to you again. I think, obviously, Jacqui hit on all the main points. I think as you rightly said at the start, we obviously do have more work to understand the biomarker population. We only really got the data in our hands about a week ago. So it's very early for us to start examining that.

謝謝你，雅基。很高興再次和你說話。我認為，顯然，Jacqui 抓住了所有要點。我認為正如你在開始時所說的那樣，我們顯然需要做更多的工作來了解生物標誌物群體。大約一周前，我們才真正拿到數據。所以我們現在開始檢查它還為時過早。

I think for me, personally, I mean as Jacqui said, I mean the fact we are able with a 3-treatment regimen to clear 36% of patients of their virus, which really is the foundation of the disease in the HPV-related disorders, is particularly promising. And I think also when you think about our RRP product, we also include IL-12 as an adjuvant, so we're hoping. And as you saw, we actually do have greater efficacy. We're able to get 81% of subjects have less surgeries than the previous year. So I think if you just put all the entirety of the data we've seen across our programs, I mean we're just confident, I think, now that we can treat HPV-related diseases.

我個人認為，正如 Jacqui 所說，我的意思是我們能夠通過 3 種治療方案清除 36% 的患者的病毒，這確實是 HPV 相關疾病的疾病基礎，特別有前途。而且我認為，當您考慮我們的 RRP 產品時，我們還包括 IL-12 作為佐劑，所以我們希望如此。正如你所看到的，我們實際上確實有更大的功效。我們能夠讓 81% 的受試者比前一年進行更少的手術。所以我認為，如果你把我們在我們的項目中看到的所有數據都放在一起，我的意思是我們有信心，我認為，現在我們可以治療 HPV 相關疾病。

And then just a follow-up on that, which is that as you've got your lead program HSIL, now RRP, GBM with Regeneron, what other preclinical targets are you looking at? I guess, these learnings are kind of coming into effect in INOVIO, are you getting sort of better visibility into the kind of preclinical targets you want to go after bringing to the clinic, so that you have greater certainty with kind of platform technology you have at DNA medicines?

然後只是對此的後續行動，那就是當你有了你的主導項目 HSIL，現在是 RRP，GBM 和 Regeneron，你還在看什麼其他臨床前目標？我想，這些學習在 INOVIO 中有點生效，您是否可以更好地了解您在進入診所後想要達到的臨床前目標類型，以便您對您擁有的平台技術有更大的確定性在 DNA 藥物？

Thanks, Hartaj. I mean that's a really interesting question. And I would say we remain focused on advancing our DNA medicine candidates that have the greatest scientific promise, clear regulatory path and strongest commercial potential. And that's really underpinned by our desire to bring to market innovative life-saving DNA medicines for the benefit of patients globally as quickly as possible.

謝謝，哈塔吉。我的意思是這是一個非常有趣的問題。我想說的是，我們仍然專注於推進具有最大科學前景、明確監管路徑和最強商業潛力的 DNA 候選藥物。我們希望盡快將創新的挽救生命的 DNA 藥物推向市場，造福全球患者，這確實支撐了這一點。

With our platform, we're able to do many different things. I mean we have candidates across infectious disease, HPV-related disease, immuno-oncology. We also have programs in early clinical development in terms of DNA-delivered monoclonal antibodies and then some further earlier preclinical work. But I think what we're really seeing now with our DNA medicines is our ability to potentially treat HPV-related diseases. I think it's going to be very interesting to see how that may translate to other chronic viral diseases. And I think we're also very excited to see what we can do in the immuno-oncology space, both in HPV-related cancers but also in some other cancers more broadly.

通過我們的平台，我們可以做很多不同的事情。我的意思是我們有傳染病、HPV 相關疾病、免疫腫瘤學的候選人。我們還有 DNA 遞送的單克隆抗體方面的早期臨床開發計劃，然後是一些更早的臨床前工作。但我認為我們現在真正看到的 DNA 藥物是我們潛在治療 HPV 相關疾病的能力。我認為看看這將如何轉化為其他慢性病毒性疾病將會非常有趣。而且我認為我們也很高興看到我們在免疫腫瘤學領域可以做些什麼，既包括 HPV 相關癌症，也包括更廣泛的其他一些癌症。

So I think the past few years, we've had a lot of data readouts, a lot of encouraging data, and we're really digging down and analyzing that data to see what it tells us and to really narrow down and focus on where do we really think the best opportunities are for DNA medicines to get potentially life-saving products to patients more quickly.

所以我認為在過去的幾年裡，我們有很多數據讀出，很多令人鼓舞的數據，我們真的在深入挖掘和分析這些數據，看看它告訴我們什麼，並真正縮小範圍並專注於哪裡我們真的認為最好的機會是讓 DNA 藥物更快地為患者提供可能挽救生命的產品嗎？

The next question is from Gregory Renza with RBC Capital Markets.

下一個問題來自 RBC Capital Markets 的 Gregory Renza。

It's Anish on for Greg. Just a quick one for me here, how should we think about the prioritization of your pipeline programs and the relative investment in each?

這是安尼什為格雷格準備的。在這裡對我來說只是一個快速的問題，我們應該如何考慮您的管道項目的優先級以及每個項目的相對投資？

Thanks. So first of all, as I mentioned in my previous response, we're really focused on advancing our DNA medicine candidates where we think we have the greatest scientific promise, the strongest commercial potential and a clear regulatory pathway going forward as well. So that's really what we're looking at as we assess and evaluate these different opportunities. We've had quite a lot of data over the recent months. We're in the process at the moment, as I said, of really sitting down, going through that data and really prioritizing how we're going to move our candidates forward and in what order. And we'll be providing some further updates on that over the coming months.

謝謝。因此，首先，正如我在之前的回應中提到的，我們真正專注於推進我們認為我們擁有最大科學前景、最強商業潛力和明確監管途徑的 DNA 候選藥物。因此，這正是我們在評估和評估這些不同機會時所關注的。最近幾個月我們有很多數據。正如我所說，我們目前正在真正坐下來，仔細研究這些數據，並真正確定我們將如何推動我們的候選人前進以及以什麼順序前進。在接下來的幾個月裡，我們將提供一些進一步的更新。

Great. And just to follow up, just the second part of my question there, is there sort of a difference in the relative investment of time and capital into each of your programs just given the prudent approach you've been taking to resource allocation?

偉大的。只是為了跟進，只是我問題的第二部分，考慮到您一直採取謹慎的資源分配方法，您對每個程序的時間和資本的相對投資是否存在某種差異？

Yes. So when we're looking across our pipeline, obviously, we're considering what the regulatory paths are, what the next steps are, likely costs, time lines, et cetera. And we're really allocating our resources across the different programs dependent on that. So I think as Mike mentioned, we're going to be sitting down and figuring out the path forward for RRP. We're currently in discussions with the regulators as to the next steps there. And then we'll be making announcements about that program over the coming months.

是的。因此，當我們審視我們的管道時，顯然，我們正在考慮監管路徑是什麼、下一步是什麼、可能的成本、時間表等等。我們實際上是在依賴於此的不同程序中分配我們的資源。所以我認為正如 Mike 提到的那樣，我們將坐下來找出 RRP 的前進道路。我們目前正在與監管機構討論下一步行動。然後我們將在未來幾個月內發布有關該計劃的公告。

For VGX-3100 as well, as you mentioned, this is very recent data. We really need to dig down into the biomarker, figure out what we can learn from this and how we might want to proceed going forward. We also have other indications for this product candidate as well that we need to take into consideration.

正如您提到的，對於 VGX-3100 也是如此，這是最近的數據。我們真的需要深入研究生物標誌物，弄清楚我們可以從中學到什麼，以及我們可能希望如何繼續前進。我們還需要考慮該候選產品的其他跡象。

The next question is from Geoff Meacham with Bank of America.

下一個問題來自美國銀行的 Geoff Meacham。

This is Charlie Yang on for Geoff. So I guess I have kind of 2-part questions. First is, I'm wondering whether you can provide some details in terms of why the biomarkers have been tested in this trial for REVEAL2. And maybe one aside, is the reason why we're not seeing a statistic here due to the fact that the number of patients enrolled were relatively small? So is the trial underpowered, and that's the reason why we're going to see a statistic in the biomarker-selected patients? And I have a follow-up after this.

這是 Geoff 的 Charlie Yang。所以我想我有兩部分的問題。首先，我想知道您是否可以提供一些詳細信息，說明為什麼在 REVEAL2 試驗中測試了生物標誌物。也許除此之外，由於登記的患者人數相對較少，我們在這裡看不到統計數據的原因是什麼？那麼試驗的功效是否不足，這就是為什麼我們要在生物標誌物選擇的患者中看到統計數據的原因？在此之後我有一個跟進。

Thanks, Geoff (sic) [Charlie]. I think those are interesting questions. So as you may recollect from the call, the biomarker-selected population was selected using our investigational biomarker.

謝謝，傑夫（原文如此）[查理]。我認為這些都是有趣的問題。因此，您可能會從電話中回憶起，生物標誌物選擇的人群是使用我們的研究性生物標誌物選擇的。

I'm going to hand it over to Mike now to provide some further details as to how we selected that biomarker and what the potential implications might be going forward. Mike?

我現在要把它交給邁克，以提供一些關於我們如何選擇該生物標誌物以及未來可能產生的潛在影響的更多細節。麥克風？

Yes. So at present, we have not disclosed what our biomarker signal was. And we'll do that, I think, in context of a full analysis of both what we saw on REVEAL1 as well as what we saw in REVEAL2 as without the sort of full details of the population and the other impacts that can affect treatment efficacy, I think it would just be a little premature for us to talk about that at the moment.

是的。所以目前，我們還沒有透露我們的生物標誌物信號是什麼。我認為，我們將在全面分析我們在 REVEAL1 和我們在 REVEAL2 中看到的內容的情況下這樣做，因為沒有人口的全部細節和可能影響治療效果的其他影響，我認為我們現在談論這個還為時過早。

To your comment around power, I mean, obviously, we did expect a higher number of subjects that have the biomarker based on what we saw in REVEAL1. But really, it wasn't a powering issue with this study. I mean we genuinely saw a lower efficacy rate from the biomarker-selected population. So that's what really makes us want to dig into the data and understand what went on in that biomarker population so that we can come back and tell people what really happened. And we're just not at the stage to do that at the moment, but we will be doing that work.

對於您關於權力的評論，我的意思是，顯然，根據我們在 REVEAL1 中看到的情況，我們確實預計會有更多的受試者俱有生物標誌物。但實際上，這不是這項研究的動力問題。我的意思是我們確實看到了生物標誌物選擇人群的較低有效率。所以這才是真正讓我們想要深入研究數據並了解該生物標誌物群體中發生的事情的原因，以便我們可以回來告訴人們真正發生了什麼。我們目前還不處於這樣做的階段，但我們會做這項工作。

Yes. And if I can just add to that, Mike. I mean, we should remember that these were trials that were not enrolled on the basis of the biomarker. The biomarker was applied retrospectively. And we had developed or defined the biomarker signature based on what we had seen in REVEAL1. And I think this was part of the reason why, in discussions with the FDA, it became clear that REVEAL2 would need to be exploratory for that biomarker-selected population.

是的。如果我可以補充一點，邁克。我的意思是，我們應該記住，這些試驗不是根據生物標誌物進行的。回顧性應用生物標誌物。我們已經根據我們在 REVEAL1 中看到的內容開發或定義了生物標記簽名。我認為這就是為什麼在與 FDA 的討論中，很明顯 REVEAL2 需要對生物標誌物選擇的人群進行探索的部分原因。

And maybe just a follow-up on a different question. So you mentioned in the press release that the cash runway is into first quarter of 2025. Can you just provide details on the assumptions in terms of your program? And how would, I guess, the next steps in terms of development for RRP and maybe the GBM will impact that cash runway?

也許只是對另一個問題的跟進。所以你在新聞稿中提到現金跑道將進入 2025 年第一季度。你能否提供有關你的計劃假設的詳細信息？我猜想，RRP 和 GBM 的下一步發展將如何影響現金跑道？

Jacqui, I'll take that.

傑基，我會接受的。

Thanks, Peter.

謝謝，彼得。

So what you're seeing is there'll be a few wind-down costs from our COVID program, but you're seeing the expenses shifting over into the RRP programs and a slight increase in the GBM programs. We still have money going into our anal programs. And then an increase in 5PSP and 3PSP developments to get those to commercial ready. Right now, probably one of the lead programs is the RRP, and that does anticipate that we get the Phase III trial started upon regulatory approval from the FDA to be able to move forward towards the end of the year, third quarter, beginning of fourth quarter. And we will cover the majority of those Phase III costs.

所以你看到的是我們的 COVID 計劃會減少一些成本，但你會看到這些費用轉移到 RRP 計劃中，並且 GBM 計劃略有增加。我們仍然有錢用於我們的肛門計劃。然後增加 5PSP 和 3PSP 的開發，使它們做好商業化準備。現在，可能其中一個主要項目是 RRP，它確實預計我們會在 FDA 的監管批准後開始 III 期試驗，以便能夠在今年年底、第三季度、第四季度初向前推進四分之一。我們將承擔大部分 III 期費用。

The next question is from Roger Song with Jefferies.

下一個問題來自 Jefferies 的 Roger Song。

Maybe a few ones for the detail. First, for the REVEAL trial, I think you mentioned the biomarker patient seems to be lower, the number of the patients seem to be lower than expected. So just curious what is the expected percentage of the biomarker-driven population will look like in a general population? And also given you now have the data set from both trials, any thoughts around how to improve upon the market strategy? I have a follow-up after that.

也許一些細節。首先，對於 REVEAL 試驗，我認為你提到生物標誌物患者似乎較低，患者數量似乎低於預期。所以很好奇生物標誌物驅動的人群在一般人群中的預期百分比是多少？並且鑑於您現在擁有兩項試驗的數據集，關於如何改進市場策略有什麼想法嗎？之後我有一個跟進。

Okay. Thanks, Roger. I'm going to hand those questions over to Mike. Mike?

好的。謝謝，羅傑。我要把這些問題交給邁克。麥克風？

Yes. So as we presented during the presentation, when you look at the REVEAL1 population, the biomarker from an efficacy level was at 65.9%. And in terms of frequency within the 201 patients in the trial, it actually accounted for 33% of those patients. So obviously, when you come on to the REVEAL2 population, there was a difference that we need to investigate there.

是的。因此，正如我們在演示期間介紹的那樣，當您查看 REVEAL1 人群時，療效水平的生物標誌物為 65.9%。就試驗中 201 名患者的頻率而言，它實際上佔了這些患者的 33%。很明顯，當你進入 REVEAL2 人群時，我們需要在那裡調查的差異。

So in terms of how to improve, I mean I think that goes back to my previous answer, we need to dig into the data and see what what's going on in the REVEAL2 data set. I mean, as Jacqui mentioned, it was an investigational biomarker. The team only had the REVEAL1 population to work on. They now have double the amount of data to look for the appropriate signature. So I think there's a lot more the team can do to really delve into the biomarker signature and see where that leads us once we've got our hands on more data.

因此，就如何改進而言，我的意思是我認為這可以追溯到我之前的回答，我們需要深入研究數據，看看 REVEAL2 數據集中發生了什麼。我的意思是，正如 Jacqui 提到的那樣，它是一種研究性生物標誌物。該團隊只有 REVEAL1 人口需要處理。他們現在有雙倍的數據量來尋找合適的簽名。所以我認為團隊可以做更多的事情來真正深入研究生物標誌物簽名，並在我們掌握更多數據後看看它會把我們引向何方。

Got it. Yes, that makes sense. And then two, for RRP, can you just remind us what is the criteria for the patient to do surgery given one of the key end points? And how consistent the criteria across size and investigation as you want to do a global trial for the later-stage development?

知道了。是的，這是有道理的。然後第二，對於 RRP，您能否提醒我們考慮到關鍵終點之一，患者進行手術的標準是什麼？當您想為後期開發進行全球試驗時，跨規模和調查的標準有多一致？

Yes. That's a really good question, Roger. And if you recollect, for our Phase I/II study, we were actually using multiple sites across the U.S. and we've been working and talking closely with KOLs and other investigators as to how we might expand the study to Europe.

是的。這是一個非常好的問題，羅傑。如果您還記得，對於我們的 I/II 期研究，我們實際上在美國使用多個站點，並且我們一直在與 KOL 和其他研究人員密切合作並討論我們如何將研究擴展到歐洲。

But I'm going to ask Mike to comment on the criteria for surgery and how variable the disease can be.

但我要請邁克評論手術的標準以及疾病的可變性。

Yes. So when you look at the sort of surgical intervention in the current trial, we didn't really specify when and how the patients could receive surgery, it was ultimately a decision between the patient and the treating clinician. As you can imagine, one of the things, because surgery is a key indicator of efficacy, we will need to try and standardize that as we move towards a registration trial. And that is going to be one of the discussions that we have with the regulatory bodies. But at present, we're not in a position that we can disclose what criteria we're thinking about. But it is an important aspect of how we design the next trial.

是的。因此，當您查看當前試驗中的手術干預類型時，我們並沒有真正具體說明患者何時以及如何接受手術，這最終是由患者和治療臨床醫生之間的決定。你可以想像，其中一件事，因為手術是療效的關鍵指標，我們需要在進行註冊試驗時嘗試標準化。這將是我們與監管機構進行的討論之一。但目前，我們無法透露我們正在考慮的標準。但這是我們如何設計下一次試驗的一個重要方面。

And if I can just add in here, what we're hearing from patients, what we're hearing from investigators, is that they really are looking for an improvement and a reduction in number of surgeries. That's the major impact on patients' lives, and that's really the thing that will move the needle for patients. So more work to do, more discussions to be had, but we really are focused on surgery.

如果我可以在這裡補充一點，我們從患者那裡聽到的，我們從研究人員那裡聽到的，是他們真的在尋求改善和減少手術次數。這是對患者生活的重大影響，也是真正為患者帶來積極影響的事情。所以要做更多的工作，要進行更多的討論，但我們真的專注於手術。

Next question is from Yi Chen with H.C. Wainwright.

下一個問題來自 Yi Chen 和 H.C.溫賴特。

First question is, the biomarker you're utilizing at REVEAL2 and REVEAL1, is that the only biomarker available? Or are there some other candidate biomarkers?

第一個問題是，您在 REVEAL2 和 REVEAL1 中使用的生物標誌物是唯一可用的生物標誌物嗎？或者還有其他一些候選生物標誌物嗎？

Yi, that's a really important question. So I'm going to hand over to Mike to talk a bit about our biomarker strategy.

易，這是一個非常重要的問題。所以我要交給邁克談談我們的生物標誌物策略。

So I always feel bad because I can't give too much information about this. The biomarker signature that we used as the primary biomarker to select the population. It was not the only biomarker that we looked at, so we will actually have more data in the database. But again, we haven't disclosed that level of detail at the moment, I'm afraid.

所以我總是感覺很糟糕，因為我不能提供太多關於這方面的信息。我們用作選擇人群的主要生物標誌物的生物標誌物特徵。它不是我們研究的唯一生物標誌物，因此我們實際上將在數據庫中擁有更多數據。但同樣，恐怕我們目前還沒有透露那麼詳細的信息。

I think what we can state though is we're working with our partner, QIAGEN, to develop these biomarkers. And this data is very new, it's very recent for us and we're going to need to dig down into it and, hopefully, come back to you with some further updates over the coming months.

我認為我們可以聲明的是我們正在與我們的合作夥伴 QIAGEN 合作開發這些生物標誌物。這些數據是非常新的，對我們來說是最近的，我們需要深入研究它，並希望在未來幾個月內為您提供一些進一步的更新。

Got it. Did the FDA say that future trials have to use a biomarker?

知道了。 FDA 是否表示未來的試驗必須使用生物標誌物？

I don't believe they stipulated that. That was our decision after we saw the data from REVEAL1 in terms of our proposal to them. I mean, what they did say that by switching to the biomarker population, it became a more exploratory study, and we would have had to do or we will have to do 1 or 2 more trials before we could file for a BLA in the biomarker investigational population.

我不相信他們有這樣的規定。這是我們在看到 REVEAL1 的數據後做出的決定，這是我們向他們提出的建議。我的意思是，他們確實說過，通過轉向生物標誌物群體，它變成了一項更具探索性的研究，在我們可以申請生物標誌物的 BLA 之前，我們將不得不或將不得不再進行 1 或 2 次試驗調查人口。

Okay. Got it. And the fact that the combined data set for both the biomarker-selected population and the all-participants population both show statistical significance, does that mean I mean that the biomarker really doesn't add much to the final results?

好的。知道了。事實上，生物標誌物選擇人群和所有參與者人群的組合數據集都顯示出統計顯著性，這是否意味著生物標誌物真的不會對最終結果增加太多？

I guess it depends what you mean by it doesn't add much. But I mean, clearly, the efficacy rate in the biomarker-selected population and the combined group was, I believe, 54%. So I mean there was a significantly increased efficacy seen in that population. So I mean, there was clearly an indication of a predictive nature of that biomarker.

我想這取決於你的意思，它不會增加太多。但我的意思是，很明顯，我相信生物標誌物選擇人群和聯合組的有效率是 54%。所以我的意思是該人群的療效顯著提高。所以我的意思是，顯然有跡象表明該生物標誌物具有預測性。

This concludes our question-and-answer session. I would like to turn the conference back over to Jacqui Shea for any closing remarks.

我們的問答環節到此結束。我想將會議轉回給 Jacqui Shea 作閉幕詞。

Thank you for your questions and to everyone joining us today.

感謝您的提問，也感謝今天加入我們的每一個人。

To summarize, as you've heard on the call today, in the past year, we've taken measured steps to prioritize our pipeline and focus our efforts on the programs with the highest probability of clinical and regulatory success and strongest commercial potential. These steps are underpinned by our commitment to operational excellence and financial discipline and our belief in the potential of DNA medicines to improve the lives of patients.

總而言之，正如您在今天的電話會議上聽到的那樣，在過去的一年裡，我們採取了慎重的步驟來確定我們的管道的優先級，並將我們的精力集中在臨床和監管成功概率最高且商業潛力最大的項目上。這些步驟的基礎是我們對卓越運營和財務紀律的承諾，以及我們對 DNA 藥物改善患者生活潛力的信念。

We're excited about our plans to advance our key programs, such as INO-3107, to the next stage of clinical development and look forward to providing you with updates on our progress in the coming quarters.

我們很高興我們計劃將我們的關鍵項目（如 INO-3107）推進到臨床開發的下一階段，並期待在未來幾個季度為您提供我們進展的最新信息。

With that, thank you again for your attention, and have a great evening, everyone.

至此，再次感謝您的關注，祝大家度過一個愉快的夜晚。

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

會議現已結束。感謝您參加今天的演講。您現在可以斷開連接。