Oncolytics Biotech Inc (ONCY) 2023 Q3 法說會逐字稿

Good morning, and welcome to Oncolytics Biotech's third-quarter 2023 conference call. (Operator Instructions) Please be advised that this call is being recorded at the company's request.

早安，歡迎參加 Oncolytics Biotech 的 2023 年第三季電話會議。 （操作員說明）請注意，本次通話是應公司要求進行錄音的。

I would now like to turn the call over to Jon Patton, Director of Investor Relations and Communication.

我現在想將電話轉給投資者關係和溝通總監喬恩·帕頓 (Jon Patton)。

Thank you, operator. And good morning, everyone. Earlier this morning, Oncolytics issued a press release providing recent operational highlights and financial results for the third quarter of 2023. A replay of today's call will be available on the events section of the Oncolytics website approximately two hours after its completion. After remarks from company management, we will open the call for Q&A.

謝謝你，接線生。大家早安。今天早些時候，Oncolytics 發布了一份新聞稿，提供了近期的營運亮點和2023 年第三季的財務業績。今天電話會議的重播將在會議結束後大約兩小時在Oncolytics 網站的活動部分提供。在公司管理階層發表演說後，我們將開始問答環節。

As a reminder, various remarks made during this call contain certain forward looking statements relating to the company's business prospects, and the development, and commercialization of pelareorep, including statements regarding the company's mission, strategy, and objectives, company's belief as to the potential, mechanism of action, and benefits of pelareorep as a cancer therapeutic, our clinical pipeline, and our belief that we are on track for licensure-enabling study in metastatic breast cancer and metastatic pancreatic cancer. The company's plans and expectations regarding the release of additional results and/or updates in respect of its ongoing clinical studies, company's business development plans and strategies, and other statements related to anticipated developments in the company's business.

謹此提醒，本次電話會議期間發表的各種言論包含與公司業務前景以及 pelareorep 的開發和商業化相關的某些前瞻性陳述，包括有關公司使命、戰略和目標、公司對潛力的信念、 Peareorep的作用機制、作為癌症治療藥物的益處、我們的臨床管道，以及我們相信我們正在順利進行轉移性乳腺癌和轉移性胰腺癌的許可研究。本公司關於發布其正在進行的臨床研究的額外結果和/或更新的計劃和期望、公司的業務發展計劃和策略以及與公司業務預期發展相關的其他聲明。

These statements are based on management's current expectations and beliefs and are subject to a number of factors which involve known and unknown risks, delays, uncertainties, and other factors not under the company's control that may cause actual results, performance or achievements of the company to be materially different from results, performance, and expectations implied by these forward-looking statements.

這些陳述是基於管理層當前的期望和信念，並受到許多因素的影響，其中包括已知和未知的風險、延誤、不確定性以及其他不受公司控制的因素，這些因素可能導致公司的實際結果、業績或成就與這些前瞻性陳述所暗示的結果、績效和預期有重大差異。

In any forward-looking statement, in which Oncolytics expresses an expectation or belief as to future results, such expectations or beliefs are expressed in good faith and are believed to have reasonable basis, but there can be no assurance that these statements or expectation or belief will be achieved. These factors include results of current or pending clinical trials, risks associated with intellectual property protection, financial projections, actions by regulatory agencies, and those other factors detailed in the company's filings with SEDAR and the SEC. Oncolytics does not undertake any obligation to update these forward-looking statements except as required by applicable laws.

在 Oncolytics 表達對未來結果的期望或信念的任何前瞻性陳述中，此類期望或信念是善意表達的，並被認為具有合理的基礎，但不能保證這些陳述或期望或信念將會實現。這些因素包括目前或即將進行的臨床試驗的結果、與智慧財產權保護相關的風險、財務預測、監管機構的行動以及公司向 SEDAR 和 SEC 提交的文件中詳細說明的其他因素。除適用法律要求外，Oncolytics 不承擔任何更新這些前瞻性聲明的義務。

Now, I'll bring on the CEO, Dr. Matt Coffey for his overall highlights and to introduce the rest of the management team who will be speaking today. Matt?

現在，我將請執行長 Matt Coffey 博士介紹他的整體亮點，並介紹今天將發言的管理團隊的其他成員。馬特？

Thank you, Jon. I'll open by saying that Oncolytics has made substantial progress since our last quarterly update, and I want to say thank you for joining us for today's call to hear about these operational highlights and third-quarter 2023 financial results.

謝謝你，喬恩。首先我要說的是，自從上一季更新以來，Oncolytics 取得了實質進展，我想說感謝您參加今天的電話會議，了解這些營運亮點和 2023 年第三季財務業績。

During the call today, our Chief Medical Officer, Tom Heineman; our Global Head of Business Development, Andrew de Guttadauro; our Chief Financial Officer, Kirk Look; and I will present an update on our clinical program, summarize the data we presented at ESMO and other recent and upcoming medical meetings to discuss our recent data readouts and other opportunities, bolster our business development efforts on potential, outlined our upcoming milestones, and provide you with our outlook on our cash runway, and summarize third-quarter financial results. Then, we'll open the call up for questions.

在今天的電話會議中，我們的首席醫療官 Tom Heineman；我們的全球業務發展主管 Andrew de Guttadauro；我們的財務長 Kirk Look；我將介紹我們臨床計劃的最新情況，總結我們在ESMO 和其他最近和即將舉行的醫學會議上提供的數據，以討論我們最近的數據讀數和其他機會，支持我們的業務發展潛力，概述我們即將到來的里程碑，並提供向您介紹我們對現金跑道的展望，並總結第三季的財務表現。然後，我們將開放提問電話。

Oncolytic intends to deliver on its mission to improve the survival of patients with cancer by investigating of novel immunotherapy, pelareorep or pela as we will refer to it, in carefully selected indications and treatment regime that will leverage its unique mechanism of action to provide the most meaningful clinical benefits. This is measured by improvements in overall survival and progression-free survival, supported by an improved T-cell profile.

Oncolytic 打算透過研究新型免疫療法（pelareorep 或 pela）來實現其提高癌症患者存活率的使命，我們將在精心選擇的適應症和治療方案中，利用其獨特的作用機制來提供最有效的治療方案。有意義的臨床益處。這是透過總生存期和無惡化存活期的改善來衡量的，並得到改善的 T 細胞譜的支持。

The data presented at the European Society for Medical Oncology or ESMO from the pancreatic and colorectal arms of the GOBLET study are a highlight of 2023. I'd like to underscore a few observations, and Tom will take you through the detailed results.

歐洲腫瘤內科學會 (ESMO) 發表的 GOBLET 研究中胰臟和結直腸組的數據是 2023 年的一大亮點。我想強調一些觀察結果，Tom 將帶您了解詳細的結果。

First, we have now met the Simon two-stage success criteria in two consecutive GOBLET cohorts evaluating pela in patients with first-line pancreatic and third-line colorectal cancer. Importantly, this is the third indication where we've seen pela combined with atezolizumab provide encouraging results in patients.

首先，我們現在在評估一線胰臟癌和第三線結直腸癌患者的 pela 的兩個連續 GOBLET 隊列中達到了 Simon 兩階段成功標準。重要的是，這是我們看到 pela 聯合 atezolizumab 為患者帶來令人鼓舞的結果的第三個適應症。

These are breast cancer with the AWARE study plus pancreatic and third-line colorectal cancer in the GOBLET study. We also continue to see the combination in pela and chemotherapy, providing response compared to historical controls, demonstrating its potential as an immune therapy backbone.

這些是 AWARE 研究中的乳癌以及 GOBLET 研究中的胰臟癌和第三線大腸直腸癌。我們也繼續看到 pela 和化療的組合，與歷史對照相比提供了反應，證明了其作為免疫治療支柱的潛力。

Additionally, we've seen the expansion of tumor-infiltrating lymphocytes or TIL clones correlated with tumor response and a strong correlation between T-cell clone expansion and improvements in the tumor microenvironment or TME consistent with pela's differentiated mechanism of action.

此外，我們還發現腫瘤浸潤淋巴細胞或TIL 克隆的擴增與腫瘤反應相關，且T 細胞克隆擴增與腫瘤微環境或TME 的改善之間存在很強的相關性，這與pela 的差異化作用機制一致。

Critically, pela treatment continues to be well tolerated which is important as we continue to evaluate additional inpatient and potential oncology treatment combinations.

至關重要的是，Pela 治療的耐受性仍然良好，這一點很重要，因為我們將繼續評估其他住院患者和潛在的腫瘤治療組合。

And finally, in addition to meeting the success criteria for both the pancreatic and colorectal cancer cohorts, the data are compelling, especially for pancreatic cancer, where we saw objective response rate, progression-free survival rates, and rates of overall survival that exceeds historical control trials.

最後，除了滿足胰腺癌和結直腸癌隊列的成功標準外，這些數據也令人信服，特別是對於胰腺癌，我們看到客觀緩解率、無進展生存率和總生存率超過了歷史水平對照試驗。

Taken together, these data show how pela's mechanism of action facilitates synergy with both chemotherapy and checkpoint inhibitors in multiple indications. Furthermore, the results expand the dataset that forms the basis of potentially compelling product profile for pela and give us additional confidence and advancing our clinical program.

總而言之，這些數據顯示了 Pela 的作用機制如何促進與化療和檢查點抑制劑在多種適應症中的協同作用。此外，結果擴展了數據集，該數據集構成了 pela 潛在引人注目的產品概況的基礎，並為我們提供了額外的信心並推進我們的臨床計劃。

We will use the results of both GOBLET segments presented at ESMO, combine with our analysis of the current treatment paradigm and competitive landscape to map out our next steps for registration studies.

我們將利用 ESMO 上展示的兩個 GOBLET 部分的結果，結合我們對當前治療範式和競爭格局的分析，來規劃我們下一步的註冊研究。

As we review Oncolytics' third quarter along with the company's recent operations, I believe there are three key take-home messages.

當我們回顧 Oncolytics 第三季以及該公司最近的營運情況時，我相信有三個關鍵資訊。

First, we believe pela has the potential to be a differentiated and effective immunotherapy that could improve the lives and overall survival of people with cancer. This is based on positive consistent results in gastrointestinal and breast cancer, including data presented at ESMO 2023 for pancreatic cancer and colorectal cancer.

首先，我們相信 pela 有潛力成為一種差異化且有效的免疫療法，可以改善癌症患者的生活和整體存活率。這是基於胃腸道癌和乳腺癌的積極一致結果，包括在 ESMO 2023 上提出的胰腺癌和大腸癌數據。

The totality of our clinical dataset shows significant improvements in tumor response and overall survival, coupled with highly correlated immunological responses measured by an improved T-cell profile in the tumor microenvironment.

我們的全部臨床數據集顯示腫瘤反應和總體生存率顯著改善，加上透過腫瘤微環境中改進的 T 細胞譜測量的高度相關的免疫反應。

Second, we are proud to be making the transition to a late-stage company running registrational trials with the upcoming start at the Phase 3 Precision Promise study in pancreatic cancer.

其次，我們很自豪能夠過渡到一家進行註冊試驗的後期公司，即將開始胰腺癌的第 3 期 Precision Promise 研究。

Another important development is the recently award of a USD5 million grant from PanCAN to support a new Phase 2 combination study in pancreatic cancer. If this study generates the same responses we've seen to date in pancreatic cancer, it could result in another pela-based combination therapy being selected for inclusion in the Precision Promise Phase 3 Platform Trial.

另一個重要進展是 PanCAN 最近授予了 500 萬美元的資助，用於支持一項新的胰腺癌 2 期聯合研究。如果這項研究產生的反應與我們迄今為止在胰腺癌中看到的反應相同，則可能會導致另一種基於 pela 的聯合療法被選擇納入 Precision Promise 3 期平台試驗。

Third, we are well positioned to advance our clinical program based on a focus on capital efficiency with a strong balance of $40 million, including USD17 million raised at an August public offering, and the overallotment plus a USD5 million PanCAN grant.

第三，我們處於有利地位，可以在註重資本效率的基礎上推進我們的臨床計劃，擁有4000 萬美元的強勁餘額，其中包括8 月份公開發行籌集的1700 萬美元，以及超額配售加上500 萬美元的PanCAN 補助。

Before I bring Tom on, I want to thank everyone on the Oncolytics team for your unwavering dedication to our mission and you're fine work.

在讓 Tom 上任之前，我要感謝 Oncolytics 團隊中的每個人對我們使命的堅定奉獻，你們做得很好。

Now I'd like to turn the call over to our Chief Medical Officer. Tom?

現在我想把電話轉給我們的首席醫療官。湯姆？

Thanks, Matt, and good morning, everyone. This morning, I would like to provide an update on our clinical programs, take you through the recent and upcoming medical meeting presentations, and close by providing you with an update on our next steps.

謝謝馬特，大家早安。今天早上，我想提供有關我們臨床計劃的最新信息，帶您瀏覽最近和即將舉行的醫學會議演示，最後向您提供有關我們後續步驟的最新信息。

As you know, we have carefully designed our clinical development program to fully explore the clinical potential of pela across a range of cancers and treatment combinations, including chemotherapy and checkpoint inhibitors or both. Our therapeutic approach takes advantage of pela's ability to induce anticancer immune responses through the introduction of its double-stranded RNA into tumor cells. This results in a range of potentially beneficial immune effects, including the induction and expansion of anti-cancer T-cells.

如您所知，我們精心設計了臨床開發計劃，以充分探索 Pela 在一系列癌症和治療組合中的臨床潛力，包括化療和檢查點抑制劑或兩者兼而有之。我們的治療方法利用了 pela 透過將其雙股 RNA 引入腫瘤細胞來誘導抗癌免疫反應的能力。這會產生一系列潛在有益的免疫效應，包括抗癌 T 細胞的誘導和擴增。

At the same time, pela also modifies the tumor microenvironment to make it less immunosuppressive, which allows more effective killing of the tumor by pela-induced immune responses. Our clinical pipeline is focused on two lead indications: HR-positive HER2-negative metastatic breast cancer and metastatic pancreatic cancer, which are on track for licensure-enabling studies. In addition, we are also investigating pela in metastatic colorectal cancer and metastatic anal cancer.

同時，pela還可以改變腫瘤微環境，使其免疫抑製程度降低，從而可以透過pela誘導的免疫反應更有效地殺死腫瘤。我們的臨床產品線主要集中在兩個主要適應症：HR 陽性 HER2 陰性轉移性乳癌和轉移性胰臟癌，這些適應症正在進行許可研究。此外，我們也正在研究 pela 在轉移性大腸直腸癌和轉移性肛門癌中的作用。

We are making excellent progress on the clinical development of pela. Starting with breast cancer, the next milestone will be a readout of survival data from the BRACELET-1 study. While we cannot precisely predict when these data will be available, we expect to be able to report results in 2024.

我們在 pela 的臨床開發方面取得了巨大進展。從乳癌開始，下一個里程碑將是 BRACELET-1 研究的生存數據讀出。雖然我們無法準確預測這些數據何時可用，但我們預計能夠在 2024 年報告結果。

In pancreatic cancer, we expect to initiate the Precision Promise Phase 3 study in the first half of 2024. This trial will compare the GOBLET study treatment regimen of pela, atezolizumab, gemcitabine, and nab-paclitaxel with the control arm of standard of care gemcitabine plus nab-paclitaxel in patients receiving first-line therapy for metastatic pancreatic cancer.

在胰臟癌方面，我們預計於 2024 年上半年啟動 Precision Promise 3 期研究。該試驗將比較 Pela、atezolizumab、吉西他濱和白蛋白結合型紫杉醇的 GOBLET 研究治療方案與標準護理吉西他濱的對照組接受轉移性胰腺癌一線治療的患者加用白蛋白結合型紫杉醇。

We are very excited to be part of the Precision Promise clinical trial. This innovative study was developed with guidance from the FDA to accelerate the registration of novel pancreatic cancer therapies. Participation in the Precision Promise clinical trial will allow efficient evaluation of the pela-based combination therapy and will reduce the cost of development by about 50% compared to a traditional pancreatic cancer Phase 3 study.

我們非常高興能夠參與 Precision Promise 臨床試驗。這項創新研究是在 FDA 的指導下進行的，旨在加速新型胰腺癌療法的註冊。參與 Precision Promise 臨床試驗將能夠有效評估基於 pela 的聯合療法，與傳統的胰腺癌 3 期研究相比，開發成本將降低約 50%。

If successful, this clinical trial is expected to support approval of the pela-based combination therapy for first-line treatment of patients with metastatic pancreatic cancer. Pending finalization of the definitive study agreement and based on the timing of regulatory feedback and the pace of enrollment, we hope to reach the initial data readout from the Precision Promise study in the first half of 2025.

如果成功，該臨床試驗預計將支持批准基於 Pela 的聯合療法用於轉移性胰腺癌患者的一線治療。在最終研究協議敲定之前，根據監管回饋的時間和入組速度，我們希望在 2025 年上半年獲得 Precision Promise 研究的初步數據讀數。

Jumping into recent and upcoming medical meeting reports, I would like to summarize the GOBLET data we presented at ESMO, touch on our SITC presentation, and briefly comment on the anal cancer cohort from the GOBLET study.

跳到最近和即將到來的醫學會議報告，我想總結一下我們在 ESMO 上展示的 GOBLET 數據，談談我們的 SITC 演示，並簡要評論 GOBLET 研究中的肛門癌隊列。

Let's start with the data presented at ESMO. As you know, GOBLET is an open-label Phase 1/2, Simon two-stage signal finding study designed to evaluate pela in combination with the PD-L1 inhibitor, atezolizumab, with or without chemotherapy in patients with different gastrointestinal cancers. The primary objective of each cohort of the study are safety and either objective response rate or disease control rate at week 16, translational data, including T-cell receptor sequencing are also being analyzed.

讓我們從 ESMO 上提供的數據開始。如您所知，GOBLET 是一項開放標籤1/2 期、Simon 兩階段訊號發現研究，旨在評估pela 與PD-L1 抑制劑atezolizumab 聯用，在不同胃腸道癌症患者中聯合或不聯合化療。每個研究隊列的主要目標是安全性，以及第 16 週時的客觀緩解率或疾病控制率，也分析了包括 T 細胞受體定序在內的轉化數據。

At ESMO, we reported updated clinical results from the pancreatic cancer and third-line colorectal cancer cohorts, including overall response rate, disease control rate, progression-free survival, and interim overall survival.

在 ESMO，我們報告了胰臟癌和第三線結直腸癌隊列的最新臨床結果，包括總體緩解率、疾病控制率、無惡化存活期和中期總體存活率。

In the pancreatic cancer cohort, a total of 13 evaluable patients with advanced or metastatic pancreatic ductal adenocarcinoma were enrolled. Patients were treated with a combination of pela, atezolizumab, gemcitabine, and nab-paclitaxel. In this cohort, 93% of patients had metastatic disease, mostly in the liver. Three or more responses at week 16 were required to meet the predefined efficacy success criteria.

在胰臟癌組中，共有 13 名可評估的晚期或轉移性胰臟導管腺癌患者入組。患者接受了 pela、atezolizumab、吉西他濱和白蛋白結合型紫杉醇的合併治療。在該隊列中，93% 的患者患有轉移性疾病，主要發生在肝臟。第 16 週需要 3 次或更多反應才能滿足預定的療效成功標準。

Updated data from this cohort showed that 8 of 13 patients had a partial response and 3 patients had stable disease. These data translate to an objective response rate of 62% of the disease control rate of 85%. We are pleased to report that this objective response rate is more than twice the rate of about 25% observed in earlier randomized studies in comparable pancreatic cancer patients.

該隊列的最新數據顯示，13 名患者中有 8 名出現部分緩解，3 名患者病情穩定。這些數據轉化為 62% 的客觀緩解率和 85% 的疾病控制率。我們很高興地報告，這一客觀緩解率是早期針對可比胰臟癌患者的隨機研究中觀察到的約 25% 的客觀緩解率的兩倍多。

Additional efficacy results as of the data cutoff of September 18, 2023, showed a median duration of response of 5.7 months, a median progression-free survival of 7.2 months, an interim median overall survival of 10.6 months, and an interim 12-month overall survival rate of 46%. Like the objective response rate outcome, these results compare favorably to those reported in prior clinical trials.

截至2023 年9 月18 日數據截止的其他療效結果顯示，中位緩解持續時間為5.7 個月，中位無惡化存活期為7.2 個月，中期中位總存活期為10.6 個月，中期整體存活期為12 個月存活率46%。與客觀緩解率結果一樣，這些結果與先前臨床試驗中報告的結果相比更為有利。

Moving to the translational results, our updated data showed that study treatment resulted in the expansion of T-cell clones, including new and pre-existing tumor-infiltrating lymphocytes or TILs. Importantly, and consistent with prior studies, expansion of TIL clones appears to correlate with tumor response. No safety signals were identified in this or any of the GOBLET cohorts consistent with our other studies.

至於轉化結果，我們的最新數據顯示，研究治療導致 T 細胞克隆的擴增，包括新的和先前存在的腫瘤浸潤淋巴細胞或 TIL。重要的是，與先前的研究一致，TIL 克隆的擴增似乎與腫瘤反應有關。在這個或任何 GOBLET 隊列中沒有發現與我們其他研究一致的安全訊號。

The updated results confirm that the pela combination therapy outperforms historical controls and provides support for advancing pela into the Phase 3 Precision Promise study.

更新的結果證實，pela 聯合療法優於歷史對照，並為將 pela 推進 3 期 Precision Promise 研究提供支持。

Next is the GOBLET colorectal cancer cohort in which pelareorep in combination with atezolizumab and then chemotherapy-preferred in tipiracil, also known as TAS-102, was evaluated in heavily pretreated patients who had received two prior lines of chemotherapy for metastatic colorectal cancer.

接下來是 GOBLET 結直腸癌隊列，其中對 pelareorep 與 atezolizumab 聯合使用，然後首選化療藥物 Tipiracil（也稱為 TAS-102）進行評估，這些患者已接受過兩種先前的轉移性結直腸癌化療方案。

Stage 1 of this cohort enrolled 15 evaluable patients of whom 4 achieved stable disease at week 16, indicating that this arm of the study also met its prespecified success criteria. Overall, six patients showed stable disease for disease control rate of 40%. It is important to note that this is a second GOBLET study cohort in a row that has met its success criteria further supported pela's ability to synergize with atezolizumab.

該隊列的第一階段招募了 15 名可評估的患者，其中 4 名患者在第 16 週時病情穩定，顯示研究組也符合其預先設定的成功標準。整體而言，6名患者病情穩定，疾病控制率為40%。值得注意的是，這是連續第二個達到成功標準的 GOBLET 研究隊列，進一步支持了 pela 與 atezolizumab 協同作用的能力。

In addition, translational data from this arm of the study demonstrated that pela increased the tumor expression of PD-L1 as well as the expansion of new T-cell clones in the blood. Therefore, these data confirm that pela has taken up by tumor cells and is able to stimulate T-cell expansion even in heavily pretreated colorectal cancer patients.

此外，該研究的轉化數據表明，pela 增加了腫瘤 PD-L1 的表達以及血液中新 T 細胞克隆的擴增。因此，這些數據證實 pela 已被腫瘤細胞吸收，即使在經過大量預處理的大腸直腸癌患者中也能夠刺激 T 細胞擴增。

These results are encouraging, given that exhaustion of tumor-infiltrating lymphocytes resulting from the late-stages of the disease and from extensive prior chemotherapy may limit their ability to expand in response to treatment.

這些結果令人鼓舞，因為疾病晚期和先前廣泛的化療導致腫瘤浸潤淋巴細胞耗盡，可能會限制它們響應治療而擴增的能力。

Moving on to SITC. We presented the translational data from the AWARE-1 breast cancer studies in an abstract with the full data from the poster expected later today. You may recall that the AWARE-1 study evaluated pela plus letrozole with and without atezolizumab in patients with HR-positive HER2-negative breast cancer. Data presented at AACR in 2021 show that this combination acted synergistically to upregulate PD-L1 expression on tumor cells and enhance the infiltration of T-cells into the tumor.

繼續轉向 SITC。我們以摘要形式介紹了 AWARE-1 乳癌研究的轉換數據，以及預計今天稍後發布的海報中的完整數據。您可能還記得，AWARE-1 研究評估了 pela 加來曲唑合併或不合併 atezolizumab 對 HR 陽性 HER2 陰性乳癌患者的治療效果。 2021 年 AACR 上公佈的數據表明，這種組合可以協同作用，上調腫瘤細胞上的 PD-L1 表達，並增強 T 細胞向腫瘤的浸潤。

The study data presented at SITC this year includes imaging mass cytometry or IMC, to study samples at a single cell level from patients who received pela, letrozole, and atezolizumab. IMC technology makes it possible to evaluate tumor immune responses and cellular interactions in the tumor microenvironment in much more detail. The results reported this year at SITC provide further support for pela's mechanism of action by demonstrating its ability to increase cytotoxic T-cells in the tumor.

今年在 SITC 上公佈的研究數據包括成像質譜流式細胞儀 (IMC)，用於研究接受 pela、來曲唑和 atezolizumab 治療的患者的單細胞水平樣本。 IMC 技術使得更詳細地評估腫瘤微環境中的腫瘤免疫反應和細胞交互作用成為可能。今年在 SITC 上報告的結果透過證明 pela 增加腫瘤中細胞毒性 T 細胞的能力，為 pela 的作用機制提供了進一步支持。

In addition, the data show that pela up-regulated PD-L1 expression in tumor tissue, potentially making tumors more amenable to checkpoint inhibitor therapy such as atezolizumab. With the game-changing availability of checkpoint inhibitors and the recognition that many patients progress or do not respond to checkpoint inhibitor treatment, there is a great deal of effort being made in the biopharmaceutical industry to find and test treatments that can turn a patient who would likely not respond to checkpoint inhibitor therapy into one who would. This may be achieved by making the tumor microenvironment more immunologically active that is to say, hot and attribute pela has demonstrated at several different cancers.

此外，數據顯示 pela 上調腫瘤組織中的 PD-L1 表達，可能使腫瘤更適合檢查點抑制劑治療，例如 atezolizumab。隨著檢查點抑制劑的出現改變了遊戲規則，並且認識到許多患者對檢查點抑制劑的治療有所進展或沒有反應，生物製藥行業正在付出巨大的努力來尋找和測試可以使患者病情轉好的治療方法。可能對檢查點抑制劑治療沒有反應的人。這可以透過使腫瘤微環境更具免疫活性來實現，也就是說，熱和屬性佩拉已在幾種不同的癌症中得到證明。

I should note that the synergy of pela with atezolizumab in breast cancer has demonstrated in the AWARE-1 study, this is what prompted Oncolytics to select atezolizumab as the checkpoint inhibitor to combined with pela and the GOBLET study of gastrointestinal cancers.

需要指出的是，pela 與 atezolizumab 在乳癌治療中的協同作用已在 AWARE-1 研究中得到證實，這促使 Oncolytics 選擇 atezolizumab 作為檢查點抑制劑，與 pela 和胃腸道癌症的 GOBLET 研究相結合。

Finally, I will touch on the anal cancer cohort of the GOBLET study. This was also designed as a Simon two-stage study. In stage one, we will enroll 10 evaluable subjects eligible for second-line or later therapy who are treated with a combination of pela and atezolizumab without chemotherapy. Two or more responses are required to meet the pre-specified success criteria and advance to stage two of the study.

最後，我將談談 GOBLET 研究的肛門癌隊列。這也被設計為西蒙兩階段研究。在第一階段，我們將招募 10 名符合二線或後續治療資格的可評估受試者，他們接受 pela 和 atezolizumab 聯合治療，無需化療。需要兩個或多個回應才能滿足預先指定的成功標準並進入研究的第二階段。

We expect to report interim results from this cohort, including preliminary objective response rate in Q4 of 2023. These results will help to shape our future development pathway for this program.

我們預計將報告該隊列的中期結果，包括 2023 年第四季度的初步客觀回應率。這些結果將有助於塑造該計劃的未來發展路徑。

Everyone at Oncolytics is genuinely pleased by pela's consistent clinical success in a series of difficult to treat cancers, which also includes HR-positive HER2-negative metastatic breast cancer as reported at ASCO last June.

Oncolytics 的每個人都對 Pela 在一系列難以治療的癌症中取得的持續臨床成功感到由衷的高興，其中還包括去年 6 月 ASCO 報告的 HR 陽性 HER2 陰性轉移性乳癌。

These clinical successes are strongly supported by the translational research results that further solidified pela's immunologic mechanism of action and make us optimistic that pela has the potential to be a highly effective immunotherapy for people with different cancers.

這些臨床成功得到了轉化研究結果的有力支持，這些結果進一步鞏固了 Pela 的免疫作用機制，並使我們樂觀地認為 Pela 有潛力成為患有不同癌症的人的高效免疫療法。

Before I hand the call over to Andrew, I would like to take a moment to thank all of the patients, caregivers, clinical investigators, study site teams, and our many collaborators for their efforts and dedication to advancing pela for the benefit of cancer patients.

在將電話轉交給 Andrew 之前，我想花點時間感謝所有患者、照護者、臨床研究人員、研究中心團隊以及我們的許多合作者，感謝他們為推進 Pela 造福癌症患者所做的努力和奉獻。

Andrew?

安德魯？

Thanks, Tom. As discussed, the positive and consistent data readouts you've seen this past month for gastrointestinal cancers, along with BRACELET-1 data for ASCO continue to keep us engaged with existing and new potential biopharma partners.

謝謝，湯姆。如所討論的，上個月您看到的胃腸癌積極且一致的數據讀數以及 ASCO 的 BRACELET-1 數據繼續讓我們與現有和新的潛在生物製藥合作夥伴保持聯繫。

On our previous financial results call, I mentioned a process of bringing some of these relationships all the way to freshen can take time. We are thrilled to be selected by Precision Promise for their adaptive Phase 3 Platform Trial with the combination of pela, gemcitabine, nab-paclitaxel, and atezolizumab in pancreatic cancer.

在我們之前的財務業績電話會議上，我提到了使其中一些關係一直保持新鮮感的過程可能需要時間。我們很高興被 Precision Promise 選擇進行其適應性 3 期平台試驗，該試驗結合了 pela、吉西他濱、白蛋白結合型紫杉醇和 atezolizumab 治療胰腺癌。

Initial pancreatic data from that treatment combination from cohort one of the GOBLET study was announced around this time last year, but being selected for Precision Promise and receiving a grant from PanCAN to explore pela with modified FOLFIRINOX in pancreatic cancer only came to light late this past summer. There was a rigorous vetting process with multiple meetings over many months with experts in key opinion leaders from PanCAN, so we are thrilled to have proven pela's potential to a well-respected global panel of experts.

GOBLET 研究之一隊列的治療組合的初始胰腺數據於去年這個時候公佈，但被選為 Precision Promise 並獲得 PanCAN 的資助以探索使用改良 FOLFIRINOX 治療胰腺癌的 pela 直到最近才曝光夏天。 PanCAN 關鍵意見領袖中的專家與 PanCAN 的關鍵意見領袖中的專家進行了數月的多次會議，進行了嚴格的審查過程，因此我們很高興向備受尊敬的全球專家小組證明了 Pela 的潛力。

The opportunity with pela in modified FOLFIRINOX could be potentially very meaningful. Standard of care for pancreatic cancer hasn't changed much for several decades, with most patients receiving either modified FOLFIRINOX or gemcitabine plus nab-paclitaxel as their first-line metastatic treatment options. A pela-based combination with gemcitabine and nab-paclitaxel will be evaluated in the Precision Promise Phase 3 study, which covers one of the treatment options for pancreatic cancer patients.

改良型 FOLFIRINOX 中 pela 的機會可能非常有意義。幾十年來，胰臟癌的護理標準沒有太大變化，大多數患者接受改良的 FOLFIRINOX 或吉西他濱加白蛋白結合型紫杉醇作為一線轉移治療選擇。 Precision Promise 3 期研究將評估基於 pela 的吉西他濱和白蛋白結合型紫杉醇的組合，該研究涵蓋了胰腺癌患者的治療方案之一。

If pela can also show similar signs of efficacy when combined with modified FOLFIRINOX with or without a checkpoint inhibitor then Oncolytics could capture significant first-line patient population and provide thousands of pancreatic cancer patients with an improvement over the currently available treatment options.

如果pela 在與有或沒有檢查點抑制劑的改良FOLFIRINOX 聯合使用時也能顯示出類似的療效跡象，那麼Oncolytics 可以捕獲大量的一線患者群體，並為數千名胰腺癌患者提供比目前可用的治療方案更好的治療方案。

Keep in mind that our BD goals remain the same. We aim to secure global clinical and commercialization partnership with a leading biopharma company under optimal terms. We already have relationships with companies like Pfizer, Merck, Roche, Incyte, and others. A number of our studies, including GOBLET and BRACELET-1 have been conducted clinical collaborations with these large pharmaceutical companies.

請記住，我們的 BD 目標保持不變。我們的目標是在最佳條件下與一家領先的生物製藥公司建立全球臨床和商業化合作夥伴關係。我們已經與輝瑞、默克、羅氏、因塞特等公司建立了合作關係。我們的多項研究，包括GOBLET和BRACELET-1，都是與這些大型製藥公司進行臨床合作的。

These collaborations have provided us with important validation support, including the agents used in the treatment combinations, working collaboratively and continuously updating them on our clinical progress, enables them to become increasingly comfortable with pela, its mechanism of action, and its potential to improve the lives of cancer patients, which we believe will serve us well in any partnering discussion.

這些合作為我們提供了重要的驗證支持，包括治療組合中使用的藥物，協同工作並不斷更新我們的臨床進展，使他們對 pela 及其作用機制及其改善治療的潛力越來越滿意。癌症患者的生活，我們相信這將對我們的任何合作討論都有好處。

I try to remind our shareholders that we can't predict the timing of any potential partnership. We will be thorough as we navigate the best possible outcome for Oncolytics and its shareholders. We hope to secure a single licensing deal for both our breast cancer pancreatic cancer programs that allows us to minimize clinical and commercial risk while providing upside through upfront payments, milestones, and royalties. As we continue to report encouraging data across multiple indications and with multiple cancer treatments, which tends to create competition among potential partners and foster continued interest. We plan to provide additional updates as appropriate and look forward to enhancing pela's value proposition.

我試圖提醒我們的股東，我們無法預測任何潛在合作夥伴關係的時間。我們將竭盡全力為 Oncolytics 及其股東爭取最佳結果。我們希望為我們的乳癌胰臟癌計畫取得單一授權協議，使我們能夠最大限度地降低臨床和商業風險，同時透過預付款、里程碑和特許權使用費提供優勢。隨著我們繼續報告多種適應症和多種癌症治療的令人鼓舞的數據，這往往會在潛在合作夥伴之間產生競爭並培養持續的興趣。我們計劃酌情提供更多更新，並期待增強 pela 的價值主張。

Now, I'll hand it to Kirk for a review of our financials. Kirk?

現在，我將把它交給柯克審查我們的財務狀況。柯克？

Thanks, Andrew. This morning, I'd like to provide an update on our cash balance for financial runway and provide you with a high-level review of our operating results for the third quarter of 2023. As a reminder, all figures are in Canadian dollars unless otherwise stated.

謝謝，安德魯。今天早上，我想提供有關我們財務跑道現金餘額的最新信息，並向您提供對我們 2023 年第三季度經營業績的高級別審查。請注意，除非另有說明，所有數字均以加元為單位指出。

First, I'll touch on our financial position, cash balance, and financial runway. I'm pleased to report we closed the third quarter with $40 million in cash and cash equivalent. During the quarter, despite the continued challenging capital market environment, we successfully closed a public offering securing over $21 million, along with the prudent use of our at-the-market facility in the first half of the year, we have raised over $30 million in 2023. With the recently announced USD5 million grant from PanCAN, we've continued to maintain a financial runway that exceeds 12 months.

首先，我將談談我們的財務狀況、現金餘額和財務跑道。我很高興地報告，第三季結束時，我們擁有 4000 萬美元的現金和現金等價物。本季度，儘管資本市場環境持續充滿挑戰，我們還是成功完成了公開發行，籌集了超過 2,100 萬美元的資金，加上上半年謹慎使用我們的市場融資，我們已籌集了超過 3,000 萬美元的資金2023年。憑藉最近宣布的PanCAN 500 萬美元撥款，我們繼續維持超過12 個月的財務跑道。

With respect to our operating results, Oncolytics continues to demonstrate remarkable fiscal responsibility. We aim to maximize our resources, ensuring that each dollar spent contributes to our R&D efforts as we move our breast and pancreatic cancer programs towards approval.

就我們的經營業績而言，Oncolytics 繼續展現出卓越的財務責任。我們的目標是最大限度地利用我們的資源，確保在乳腺癌和胰腺癌計畫獲得批准的過程中，所花費的每一美元都有助於我們的研發工作。

The research and development expenses for the third quarter of 2023 were $5.8 million compared to $3.7 million for the same period in 2022. The change mainly reflecting higher manufacturing expenses as we scale up our production process and work to comply with the changing environmental standards. Specifically, during the quarter, we completed a scaled-up engineering production line along with the associated batch testing.

2023 年第三季的研發費用為 580 萬美元，而 2022 年同期為 370 萬美元。這項變更主要反映了隨著我們擴大生產流程並努力遵守不斷變化的環境標準，製造費用增加。具體來說，本季我們完成了一條放大的工程生產線以及相關的批量測試。

General and administrative expenses for the third quarter of 2023 were $5.2 million, and this compares with $2.4 million for the same period in 2022.

2023 年第三季的一般及管理費用為 520 萬美元，而 2022 年同期為 240 萬美元。

The change was mainly associated with higher Investor Relations activities, along with a portion of the transaction costs associated with our public offering allocated to G&A expenses.

這項變更主要與投資者關係活動的增加以及與我們的公開發行相關的部分交易成本分配給一般管理費用有關。

Net loss for the third quarter of 2023 was $9.9 million or $0.14 per share on 69.8 million weighted average shares outstanding. This compares with a net loss for the third quarter of 2022 of $4.4 million or $0.08 per share.

2023 年第三季的淨虧損為 990 萬美元，即 6,980 萬股加權平均已發行股票，每股虧損 0.14 美元。相比之下，2022 年第三季的淨虧損為 440 萬美元，即每股虧損 0.08 美元。

Finally, with our prudent financial management, combined with our ability to secure funding in this tough equity capital market, we're well positioned for 2024 and achieving our development milestones.

最後，憑藉我們審慎的財務管理，加上我們在嚴峻的股權資本市場中獲得融資的能力，我們為 2024 年做好了充分準備，實現了我們的發展里程碑。

With my financial review complete, I'll now hand the call back to Matt for concluding remarks. Matt?

財務審查完成後，我現在將把電話轉回給馬特以進行總結發言。馬特？

Thank you, Kirk. In closing, I want to come back to our three key take-home messages.

謝謝你，柯克。最後，我想回到我們的三個關鍵訊息。

First, we believe pela has the potential to be a differentiated and effective immunotherapy that can improve the lives and overall survival of people with cancer.

首先，我們相信 pela 有潛力成為一種差異化且有效的免疫療法，可以改善癌症患者的生活和整體存活率。

Second, we are proud to be making the transition to be coming of late-stage company running registrational studies with the start of the Phase 3 Precision Promise study in pancreatic cancer on the horizon.

其次，隨著胰臟癌第 3 期 Precision Promise 研究即將開始，我們很自豪能夠過渡到開展註冊研究的後期公司。

Third, we are well positioned to advance our clinical program space on a solid cash balance that gets us to keep data readout milestones.

第三，我們處於有利地位，可以在堅實的現金餘額上推進我們的臨床專案空間，這使我們能夠保持資料讀出的里程碑。

Looking ahead to the rest of the year and into 2024, we are focused on achieving the following milestones.

展望今年剩餘時間和 2024 年，我們致力於實現以下里程碑。

Later today, we will be presenting additional cellular immune data from the AWARE study, demonstrating how pela replication in the presence of atezolizumab derives the immune cells into the TME and homes them to the infected cancer cells. By the end of the year, we expect to provide an update on the fourth cohort from the GOBLET trial in patients with anal cancer.

今天晚些時候，我們將展示更多來自 AWARE 研究的細胞免疫數據，展示在 atezolizumab 存在的情況下 pela 複製如何將免疫細胞引入 TME 並將其歸巢到受感染的癌細胞中。到今年年底，我們預計將提供針對肛門癌患者的 GOBLET 試驗第四組的最新資訊。

In the first half of 2024, we expect to announce the start of Phase 3 Precision Promise study in pancreatic cancer. This is a combination study with pela, nab-paclitaxel, gemcitabine, and the checkpoint inhibitor, atezolizumab, solidifying Oncolytics as a late-stage clinical opportunity.

2024 年上半年，我們預計將宣布啟動胰臟癌 3 期 Precision Promise 研究。這是一項使用 pela、白蛋白結合型紫杉醇、吉西他濱和檢查點抑制劑 atezolizumab 的聯合研究，鞏固了溶瘤藥物作為後期臨床機會的地位。

Also, in the first half of 2024, we will initiate a new arm in the GOBLET study, evaluating pela in combination with modified FOLFIRINOX with or without atezolizumab in patients with early-stage pancreatic cancer, supported in part by the USD5 million grant we received from PanCAN.

此外，在2024 年上半年，我們將在GOBLET 研究中啟動一個新小組，評估pela 與改良版FOLFIRINOX 聯合使用或不使用atezolizumab 治療早期胰腺癌患者的效果，部分由我們收到的500 萬美元資助提供支持來自 PanCAN。

Also, we expect to report survival data from the BRACELET-1 study in patients with HR-positive HER2-negative breast cancer. The timing to report these results is linked to the number of progression events defined as disease progression or death. While it's not possible to predict the exact timing for survival data, we believe that may be available before the end of 2024. We are evaluating next steps for this indication and plan to provide investors with a further update on our plans in 2024.

此外，我們預計將報告 BRACELET-1 研究中 HR 陽性 HER2 陰性乳癌患者的存活數據。報告這些結果的時間與定義為疾病進展或死亡的進展事件的數量有關。雖然無法預測生存數據的確切時間，但我們相信可能會在 2024 年底之前提供。我們正在評估這一跡象的後續步驟，並計劃在 2024 年向投資者提供有關我們計劃的進一步更新。

Now before we sign off, I want to thank our investors, investigators, and collaborators for supporting Oncolytics. I'm also grateful for the patients participating in our clinical trials and our fantastic employees for their hard work. We are dedicated to leveraging pela's unique mechanism of action to improve the care and survival of patients with cancer, and we look forward to keeping you informed about our progress.

現在，在我們結束之前，我要感謝我們的投資者、研究人員和合作者對 Oncolytics 的支持。我還感謝參與我們臨床試驗的患者以及我們出色的員工的辛勤工作。我們致力於利用 Pela 獨特的作用機制來改善癌症患者的照護和生存，我們期待隨時向您通報我們的進展。

Operator, we can now open the line for questions.

接線員，我們現在可以開通提問線路了。

(Operator Instructions) Louise Chen, Cantor.

（操作員說明）Louise Chen，Cantor。

Hi. Congratulations on all the progress this quarter, and thank you for taking my question.

你好。恭喜本季取得的所有進展，並感謝您提出我的問題。

So I wanted to ask you about BRACELET-1, and if there's any new data or updates that give you incrementally more confidence that you'll show some good overall survival data?

所以我想問您有關 BRACELET-1 的問題，是否有任何新數據或更新可以讓您更有信心展示一些良好的整體生存數據？

And then secondly, for the GOBLET anal data, what exact data are you planning to show in the interim? Are you going to put out a press release? And then if you are going to show data, what do you think would be competitive data or how do you think about what you'd ideally like to see?

其次，對於 GOBLET 肛門數據，您計劃在此期間顯示哪些確切數據？您要發布新聞稿嗎？然後，如果您要展示數據，您認為什麼是有競爭力的數據，或者您如何看待您最希望看到的數據？

And then last question on your partnership is, have you started those discussions yet? And ideally, what kind of partner would be good for you? Somebody global, somebody involved in oncology. What are you thinking about here? Thank you.

關於你們的夥伴關係的最後一個問題是，你們已經開始這些討論了嗎？理想情況下，什麼樣的合作夥伴對您有好處？一個全球性的人，一個涉足腫瘤學的人。你在想什麼？謝謝。

Sure. Hi, Louise. Thanks for the questions. Your first question was about breast cancer and the BRACELET data. You can tell we're a little bit cautious about saying when we would have the overall survival of them. What makes me really quite excited about the evolving data is we reported at ESMO or around ESMO, patients receiving paclitaxel. None of them unfortunately made a progression past 12 months. And for the pela plus [real] arm, we were seeing 33% [absolute number was]. We're still actually tracking patients on the pela and paclitaxel arm who were at or above two years now without progressing.

當然。嗨，路易絲。感謝您的提問。你的第一個問題是關於乳癌和 BRACELET 數據。你可以看出，我們對於何時才能讓他們整體生存感到有點謹慎。讓我對不斷變化的數據感到非常興奮的是，我們在 ESMO 或 ESMO 周圍報告了接受紫杉醇治療的患者。不幸的是，在過去的 12 個月裡，他們都沒有取得進展。對於 pela plus [真實] 手臂，我們看到 33% [絕對數字是]。實際上，我們仍在追蹤使用 pela 和紫杉醇治療組的患者，這些患者已經兩年或兩年以上，但沒有任何進展。

So for in metastatic breast cancer setting, this is a remarkable outcome for these patients. But as you can tell, if the patients haven't progressed, they also haven't died. So we're still collecting the overall survival data. We do believe we'll have the events in 2024. But as I said, we're still tracking a number of the patients on the test arm for just PFS, so that's a fabulous outcome. That's why we have the confidence, frankly, is just because there's still participating on study.

因此，對於轉移性乳癌患者來說，這是一個了不起的結果。但正如你所知，如果患者沒有進展，他們也沒有死亡。所以我們仍在收集總體存活數據。我們確實相信我們會在 2024 年舉辦這些活動。但正如我所說，我們仍在追蹤測試組中的一些患者的 PFS，所以這是一個非常棒的結果。所以我們有信心，坦白說，就是因為還有參與學習。

In terms of the anal cancer, what we will be looking for there, likely as response data like the rest of the GOBLET, what the primary endpoint was objective response. I hear what we mean for success is 2 out of 10 patients or better. That one is really quite exciting as well because if you look at it, it's simply atezolizumab with pela. There is no chemotherapy.

就肛門癌而言，我們將在那裡尋找什麼，可能是像「GOBLET」的其餘部分一樣的反應數據，主要終點是客觀反應。我聽說我們所說的成功指的是十分之二的患者或更好。這也確實非常令人興奮，因為如果你看一下它，它就是阿特朱單抗和佩拉。沒有化療。

So this is a pretreated patient population in the second-line setting. If we do see responses, it would be due to the drug combination, atezolizumab plus pela, so no one can make the argument. Well, maybe it was chemo. What have you?

因此，這是在二線環境中經過預處理的患者群。如果我們確實看到了反應，那將是由於阿特朱單抗加佩拉這一藥物組合所致，所以沒有人可以提出論點。嗯，也許是化療。你有什麼？

Now in terms of what the objective response rate in this population is it's going to be historically around 10% to 13%. Incyte recently reported on a study in that patient population. I think it was 90 to 100 patient ballpark where they reported the most recently -- they had three studies, one reported at 10% response, one was 11%, one was 13%.

現在就該族群的客觀反應率而言，歷史上將在 10% 至 13% 左右。 Incyte 最近報告了針對該患者群體的一項研究。我認為他們最近報告的大約是90 到100 名患者——他們進行了三項研究，一項報告的反應率為10%，一項報告的反應率為11%，一項報告的反應率為13 %。

So if we see anything in excess of that, especially if the responses are dramatic deep and lasting, I think it sets us on quite a successful course because as you know, anal cancer in the second line has no treatment options. It is a clear unmet need area, so if we see anything I think in excess of this 13%, we're off to the races, if you will.

因此，如果我們看到任何超出這一範圍的情況，特別是如果反應非常深刻且持久，我認為這將使我們走上相當成功的道路，因為如您所知，二線肛門癌沒有治療選擇。這是一個明顯未滿足的需求領域，所以如果我們看到任何我認為超過這 13% 的內容，我們就開始競爭，如果你願意的話。

In terms of partnering, we're in discussions with a number of groups. Really what everyone's looking for, I think, and I think the catalyst, I think this -- what we're striving for as well. The PanCAN study is being run with atezolizumab. Obviously, that's going to be generating randomized data with substantial end. I think that is potentially an inflection point.

在合作方面，我們正在與多個團體進行討論。我認為，這確實是每個人都在尋找的東西，也是我們正在努力爭取的催化劑。 PanCAN 研究正在使用 atezolizumab 進行。顯然，這將產生具有實質結果的隨機數據。我認為這可能是個拐點。

On the breast cancer side, what we'd like to do is -- looking at trial design very similar to the PanCAN where we can get an interim look, which provides us and partners with the confidence that this drug combination is active. Again, the data that we've presented, two randomized studies is very compelling, both of them having reached their endpoints, both of them being either statistically significant for survival of case 90 through 13 or as you can see with the confidence intervals on the BRACELET today that didn't cross one. It does speak to the fact that it is statistically significant even in a small group, but we want to be able to generate basically additional data with the parties, so that everyone can come in prior to the conclusion of the Phase 3 very much like in the PanCAN situation.

在乳癌方面，我們想做的是——看看與 PanCAN 非常相似的試驗設計，我們可以在其中進行中期觀察，這讓我們和伴侶相信這種藥物組合是有效的。同樣，我們提供的數據，兩項隨機研究非常引人注目，兩項研究都達到了終點，兩項研究對於病例90 至13 的生存都具有統計顯著性，或者正如您可以從置信區間看到的那樣今天的手鍊沒有交叉。它確實說明了這樣一個事實：即使在一個小群體中，它也具有統計顯著性，但我們希望能夠與各方一起產生基本上額外的數據，以便每個人都可以在第三階段結束之前加入，就像在PanCAN 的情況。

So that being said, we've been very fortunate with our work with atezolizumab. We've now got three out of three successful studies that being -- the AWARE, which demonstrated the synergy with atezolizumab in terms of enhancing that CelTIL score, enhancing the inflammation and improving the quality of it.

話雖這麼說，我們在阿特珠單抗方面的工作非常幸運。我們現在已經獲得三分之三的成功研究，即 AWARE，它證明了與 atezolizumab 在提高 CelTIL 評分、增強發炎和改善發炎品質方面的協同作用。

The data we're presenting today at SITC with the IMC really is a much more granular look of which cells are being recruited, where we're seeing inflammation, and this is really at the cellular level. So what we're looking at here is the infected cells and which cells are being recruited to eliminate that cells. Whether it would be macrophage, MDSC, CD8, 4 cells, T memory, T helper. So it gives us a very granular look of what's happening, but it is very clear that this is driving immunological response.

我們今天在 SITC 上與 IMC 一起展示的數據確實更詳細地了解了哪些細胞正在被招募，我們在哪裡看到了炎症，這實際上是在細胞層面。所以我們在這裡關注的是被感染的細胞以及正在招募哪些細胞來消除這些細胞。是否為巨噬細胞、MDSC、CD8、4 細胞、T 記憶、T 輔助細胞。因此，它讓我們對正在發生的事情有一個非常細緻的了解，但很明顯，這正在推動免疫反應。

Also, successful is -- it was the pancreatic study, which led to the PanCAN study and now more recently with third-line colorectal, where again, we met the primary endpoint. So it's very clear that our synergy with atezolizumab and presumably other PD-L1 inhibitors. GOBLET, assuming that the results are positive, this would be the fourth study in a row that would show synergy with atezolizumab.

此外，成功的是——正是胰臟研究導致了 PanCAN 研究，現在又進行了三線結直腸研究，我們再次達到了主要終點。因此，很明顯我們與 atezolizumab 以及其他 PD-L1 抑制劑具有協同作用。 GOBLET，假設結果是正面的，這將是連續第四項顯示與 atezolizumab 協同作用的研究。

So I think for parties looking at this as a partnering opportunity, even though the ends are small, their cumulative consistent, and reproducible. So I think that will drive some of the discussions as well. And as Andrew pointed to, we've always wanted to be very competitive across our partnerships. So what we are looking for as large biopharma that can take on a global role with us to take the indications where we already know we're successful that being PDAC and metastatic breast cancer and then expand that into other areas as well.

因此，我認為對於將其視為合作機會的各方來說，即使目標很小，但其累積的一致性和可重複性。所以我認為這也會推動一些討論。正如安德魯所指出的，我們一直希望我們的合作關係具有強大的競爭力。因此，我們正在尋找能夠與我們一起發揮全球作用的大型生物製藥公司，在我們已經知道的 PDAC 和轉移性乳癌領域取得成功，然後將其擴展到其他領域。

I mean for us right now, the goal is to get that approval, so that we can expand access across multiple indications in settings to just provide more patients with the opportunity to receive it because we really are quite impressed with the results that we are seen as it relates.

我的意思是，對我們來說，現在的目標是獲得批准，這樣我們就可以擴大對多種適應症的訪問，為更多的患者提供接受它的機會，因為我們對所看到的結果印象深刻正如它所涉及的。

Tom, was there anything you wanted to add either on the breast side or on anal cancer?

湯姆，對於乳癌或肛門癌，您有什麼想要補充的嗎？

No, other than to emphasize that we've now seen consistent success across the HR-positive HER2-negative breast cancer. We've met the success criteria, obviously in pancreatic cancer and colorectal cancer. And with the anal carcinoma report coming up, I think everything is looking very promising.

不，除了強調我們現在已經在 HR 陽性和 HER2 陰性乳癌治療中取得了一致的成功。我們已經達到了成功標準，尤其是在胰臟癌和大腸癌方面。隨著肛門癌報告的出現，我認為一切看起來都非常有希望。

John Newman, Canaccord Genuity LLC.

約翰紐曼 (John Newman)，Canaccord Genuity LLC。

Hi, guys. Good morning. Thank you for taking the question. And good work on those progress here.

嗨，大家好。早安.感謝您提出問題。並在這些進展方面做得很好。

I had a question about the PanCAN study. I believe you mentioned you'll be starting that in the first half of '24, the Phase 1/2 study. What I'm curious about is, are you able to treat through progression with pelareorep?

我對 PanCAN 研究有疑問。我相信您提到您將在 24 年上半年開始 1/2 期研究。我很好奇的是，你可以用 pelareorep 進行治療嗎？

So obviously, as patient is being treated with chemotherapy or PD-1, those therapies are not always continued through progression, but wondering if you're able to do that with just pelareorep? Thanks.

顯然，當患者接受化療或 PD-1 治療時，這些治療並不總是在疾病進展過程中持續進行，但您想知道是否能夠僅透過 pelareorep 來做到這一點？謝謝。

I got to push Tom under the bus on that one. Tom, can you speak to the plan in terms of dosing on the modified FOLFIRINOX study?

我必須把湯姆推到公車底下。 Tom，您能就修改後的 FOLFIRINOX 研究的劑量談談該計劃嗎？

So we -- so for the Precision Promise study, which is the gemcitabine, nab-paclitaxel, pelareorep, and atezo; in that study, the protocol -- and again, this protocol has been -- was written in -- with guidance from the FDA and has been highly vetted. In that protocol, there is no treatment past progression.

所以我們——對於 Precision Promise 研究，它是吉西他濱、白蛋白結合型紫杉醇、pelareorep 和 atezo；在那項研究中，該方案——再說一次，該方案是在 FDA 的指導下編寫的，並且經過了嚴格審查。在該方案中，沒有進展後的治療。

We are also doing the -- adding the additional arm to the GOBLET study where we're combining pelareorep with modified FOLFIRINOX plus or minus atezolizumab. And in that study, we do have the option to treat past progression.

我們還在 GOBLET 研究中添加額外的手臂，其中我們將 pelareorep 與改良的 FOLFIRINOX 加或減 atezolizumab 結合起來。在這項研究中，我們確實可以選擇治療過去的進展。

Sumeet fine from Zoran's research.

蘇米特·佐蘭（Zoran）的研究很好。

Good morning, everyone, and congrats on all the progress. Going back to the ESMO presentation on the pancreatic data, it looks like -- would the real comparative study -- would be the -- trial with liposomal irinotecan and the OS is coming close to it. So I'm curious in the frontline setting, are you thinking the modified FOLFIRINOX arm is a better option where you can see a very clear benefit in a larger patient cohort? What's your thinking like?

大家早安，祝賀所有的進展。回到 ESMO 關於胰臟數據的演示，看起來真正的比較研究將是脂質體伊立替康的試驗，而 OS 正在接近它。所以我很好奇，在前線環境中，您是否認為改良的 FOLFIRINOX 臂是更好的選擇，您可以在更大的患者群體中看到非常明顯的好處？你的想法是怎樣的？

We -- I read your report. Thank you for that, by the way. Looking at the NAPOLI study, I would argue that that patient population, since they've not had previous exposure to any chemotherapy and there were predominantly not in metastatic setting as to our, I wouldn't say that's an apples to apples comparison. Also, it was an odd study, and that is basically a derivative of modified FOLFIRINOX in that comparative to nab-paclitaxel, I would have thought a better comparator would have been modified FOLFIRINOX as the comparator arm because gem, nab-paclitaxel basically -- the thinking is it's not as active, but you don't pay tox penalty in a way that you would with modified FOLFIRINOX. So I would argue that NAPOLI study has a few fundamental differences and flaws that make the comparisons difficult.

我們——我讀了你的報告。順便說一句，謝謝你。看看 NAPOLI 研究，我認為患者群體，因為他們以前沒有接受過任何化療，而且與我們相比，主要沒有處於轉移環境，我不會說這是一個同類的比較。另外，這是一項奇怪的研究，基本上是改良型FOLFIRINOX 的衍生物，與白蛋白結合型紫杉醇相比，我本以為更好的比較器會被改良為FOLFIRINOX 作為比較臂，因為寶石，白蛋白結合型紫杉醇基本上——我們的想法是它不那麼活躍，但您不必像使用改良版 FOLFIRINOX 那樣支付毒性罰款。因此，我認為 NAPOLI 研究存在一些根本差異和缺陷，導致比較變得困難。

In terms of PanCAN's interests with modified FOLFIRINOX, there is a lot of clinicians that prefer because there is the thinking that it is more active, although recent publications at ESMO from the -- I'm just trying to think that the group that did it. It's SOLTI -- pardon me, it's the group that published it, would suggest that maybe the differences that as much as you can see. That being said, modified FOLFIRINOX is going to be used as one of the frontline treatment options.

就 PanCAN 對改良 FOLFIRINOX 的興趣而言，有很多臨床醫生更喜歡，因為他們認為它更活躍，儘管最近在 ESMO 上發表的文章——我只是想認為做這件事的小組。這是 SOLTI——請原諒，這是發布它的小組，可能會暗示您可能看到的差異。話雖如此，改良的 FOLFIRINOX 將被用作一線治療選項之一。

PanCAN did want to study it to see if it is more active, if we can enhance that activity with pelareorep and atezolizumab, but it is an experiment. We're very delighted that PanCAN provided a $5 million grant for us to do this, but we won't know the activity until we actually got treated. I mean, I believe it's going to be more active. But on the flip side, it's a lot more drugs. The toxicity could be unacceptable. We've never seen that before, but it is possible, but it could also be that the modified FOLFIRINOX interferes with the T-cell response as well, because there is so many drugs present. So we're running the experiment to see what the activity looks like.

PanCAN 確實想研究它，看看它是否更活躍，我們是否可以用 pelareorep 和 atezolizumab 增強這種活性，但這只是一個實驗。我們非常高興 PanCAN 為我們提供了 500 萬美元的資助來完成這項工作，但在我們真正接受治療之前我們不會知道這項活動。我的意思是，我相信它會更加活躍。但另一方面，它是更多的毒品。毒性可能是不可接受的。我們以前從未見過這種情況，但有可能，但也可能是改良後的 FOLFIRINOX 也會幹擾 T 細胞反應，因為有這麼多的藥物。所以我們正在運行實驗來看看活動是什麼樣的。

What's nice about that one is it is a randomized protocol, so it's modified FOLFIRINOX, pela, plus or minus atezolizumab. So we'll have a better look at the contribution. But again, I'm not anticipating there would be any toxicities with pela because it is a well-tolerated to date. Pela-atezolizumab combinations have been well tolerated as well. But with a new drug combination, it is always a little bit of uncertainty. But certainly we have the backing of a very prestigious group like PanCAN to study that, so the belief is that we will be more active and we'll know later next year.

此方案的優點在於它是一項隨機方案，因此它修改了 FOLFIRINOX、pela，加上或減去 atezolizumab。因此，我們將更好地了解貢獻。但同樣，我並不認為佩拉會有任何毒性，因為迄今為止它的耐受性良好。 Pela-atezolizumab 組合也具有良好的耐受性。但對於新的藥物組合，總是存在一點不確定性。但我們確實得到了像 PanCAN 這樣非常有聲望的團體的支持來研究這個問題，所以我們相信我們會更加積極，明年晚些時候我們就會知道。

Tom, do you have anything to add about that NAPOLI study? Tom, you might be on mute.

湯姆，關於那不勒斯的研究你還有什麼要補充的嗎？湯姆，你可能處於靜音狀態。

Yeah, terribly sorry. Yeah, the NAPOLI study was certainly an interesting study, but it didn't really, for the reasons Matt mentioned, it didn't really answer all the questions. And I think the pela plus FOLFIRINOX study will be very interesting. And it's not that there's a obvious reason why pela should work better with FOLFIRINOX, although -- but we have reasons to believe that it may work with FOLFIRINOX and some clinicians for different reasons in different parts of world simply prefer FOLFIRINOX over the gemcitabine and nab-paclitaxel for some of their patients.

是的，非常抱歉。是的，那不勒斯的研究確實是一項有趣的研究，但它並不是真的，因為馬特提到的原因，它並沒有真正回答所有問題。我認為 pela 加 FOLFIRINOX 研究將會非常有趣。這並不是說pela 應該與FOLFIRINOX 一起更好地發揮作用，儘管如此，但我們有理由相信它可能與FOLFIRINOX 一起發揮作用，而且世界不同地區的一些臨床醫生出於不同原因更喜歡FOLFIRINOX，而不是吉西他濱和nab - 紫杉醇用於他們的一些患者。

So by investigating pela in combination with the modified FOLFIRINOX, we are able -- we would be able to cover the entire pancreatic cancer first-line population, right? So it expands our ability to provide benefit to patients regardless of physicians own particular perspectives on the standard of care treatment.

因此，透過研究 pela 與改良版 FOLFIRINOX 的結合，我們能夠——我們將能夠涵蓋整個胰腺癌一線人群，對吧？因此，無論醫生對護理治療標準有什麼特殊看法，它都擴大了我們為病人提供福利的能力。

And also just to comment on the safety side, we have never combined pela with modified FOLFIRINOX, but in other studies, we have combined pela with the components of FOLFIRINOX in -- so we -- although you never know for sure, we don't have any reason to believe that it will be poorly with any of the components of the FOLFIRINOX.

另外，只是為了評論安全性，我們從未將pela 與改良的FOLFIRINOX 結合使用，但在其他研究中，我們將pela 與FOLFIRINOX 的成分結合起來——所以我們——儘管你永遠無法確定，但我們不知道沒有任何理由相信它會與 FOLFIRINOX 的任何成分產生不良反應。

I must say that was very helpful. Now the question is, I know it's probably not an enrollment criteria, but are you looking into the -- any biomarkers of these 13 patients in terms of genetic biomarker or PD-L1 levels, something to explain the non-responders or patients who are seeing on a shorter duration of response? Any anything you're seeing there?

我必須說這非常有幫助。現在的問題是，我知道這可能不是入組標準，但是您是否正在研究這 13 名患者的遺傳生物標記或 PD-L1 水平的任何生物標誌物，以解釋無反應者或有反應的患者看到反應時間較短嗎？你在那裡看到了什麼嗎？

The one biomarker that I'm very interested in is the expansion of the tumor-infiltrating lymphocytes that we've demonstrated correlates to tumor response. So for anyone not familiar with the story, we were able to -- and it was a question on Roche actually. They said, is there any correlation with the existing T-cells and tumor response.

我非常感興趣的生物標記是腫瘤浸潤淋巴細胞的擴張，我們已經證明它與腫瘤反應有關。因此，對於任何不熟悉這個故事的人來說，我們能夠——這實際上是關於羅氏的問題。他們說，現有的T細胞和腫瘤反應有什麼相關性嗎？

So we went back -- and again, this is all the TCR work. We looked at the resident T-cells within the tumor resident cells at baseline. And the reason for that is the assumption is if you have inflammatory cells within the tumor that are most likely directed against the tumor, so this isn't autoreactive T-cell that's become exhausted. So we wanted to look what happens to those cells post treatment.

所以我們回去了——這就是 TCR 的全部工作。我們在基線時觀察了腫瘤駐留細胞內的駐留 T 細胞。原因是假設腫瘤內是否存在最有可能針對腫瘤的發炎細胞，因此這並不是耗盡的自身反應性 T 細胞。所以我們想看看這些細胞在治療後會發生什麼事。

And what we are able to demonstrate is in the responders, those TILs, we could see those clones expanding in the blood. So we know we're actually getting in an expansion of pre-existing T-cells that do recognize the tumor, and we can look at that as early as two to three weeks.

我們能夠證明的是，在反應者中，那些 TIL，我們可以看到這些克隆在血液中擴張。所以我們知道我們實際上正在擴增預先存在的能夠辨識腫瘤的 T 細胞，我們最早可以在兩到三週內進行觀察。

So we can immunologically say these patients had an exhausted T-cell clone that was useful in eliminating the tumor and the combination of atezolizumab and pela. We're able to expand those populations to eliminate the tumor more effectively. So it speaks to the immunological status we can measure quickly and it appears to be reproducible. So I think for us, it allows us really to start guessing which patients are going to have better immunological outcomes.

因此，我們可以從免疫學上說，這些患者的 T 細胞克隆已耗盡，這有助於消除腫瘤以及阿特朱單抗和佩拉的組合。我們能夠擴大這些群體，從而更有效地消除腫瘤。因此，它說明了我們可以快速測量的免疫狀態，而且它似乎是可重複的。所以我認為對我們來說，它讓我們真正開始猜測哪些患者會有更好的免疫結果。

Tom, you are closer to the protocols. Are any of the biomarkers that we're looking at?

湯姆，你更接近協議了。我們正在研究哪些生物標記？

So we are looking at a variety of different markers. But I think to date, as you point out, Matt, the TIL expansion is the one that -- be the most -- it has the best correlation with response and is also consistent with the prior literature. So I think that's probably the most interesting one that we've identified so far.

所以我們正在研究各種不同的標記。但我認為，正如您所指出的，馬特，TIL 擴展是迄今為止與回應相關性最好的擴展，並且與先前的文獻一致。所以我認為這可能是迄今為止我們發現的最有趣的一個。

There's some additional work being done with CCAM 6. If you're familiar with the literature, Dr. Anne Noonan at OSU has demonstrated that patients with better outcomes have lower CCAM 6 levels. That was in the NCI study looking at this. So we are verifying that result as well because that could be a selection criteria based on post-treatment, but pretreatment. So we'll have additional information for you there in that area as well.

目前正在針對 CCAM 6 進行一些額外的工作。如果您熟悉相關文獻，OSU 的 Anne Noonan 博士已經證明，預後較好的患者的 CCAM 6 水平較低。 NCI 的研究對此進行了研究。因此，我們也正在驗證該結果，因為這可能是基於治療後而非治療前的選擇標準。因此，我們還將為您提供該領域的更多資訊。

Nothing you're seeing on the KRAS G12C mutation of DNA damage response pathway mutations?

您在 DNA 損傷反應途徑突變的 KRAS G12C 突變上沒有看到什麼嗎？

Just -- so in pancreatic cancer, the large majority of patients somewhere in the 80%-plus will have a KRAS mutation. So that is unlikely to be discriminatory in that particular patient population.

只是——所以在胰臟癌中，80% 以上的大多數患者都會有 KRAS 突變。因此，這對於特定的患者群體來說不太可能存在歧視。

(Operator Instructions) (Operator Instructions) Jason McCarthy, Maxim Group.

（操作員說明） （操作員說明）Jason McCarthy，Maxim Group。

Hi, guys. This is Chad on for Jason. Thanks for taking the question. So I was just wondering in the same way, you got the grant from PanCAN around a different combo and pancreatic, do you think there would be a similar opportunity in breast cancer, say, evaluating pela with a different checkpoint than as used in BRACELET-1?

嗨，大家好。這是查德（Chad）代替傑森（Jason）。感謝您提出問題。所以我只是想以同樣的方式想知道，你從PanCAN 獲得了圍繞不同組合和胰腺的資助，你認為在乳腺癌方面是否會有類似的機會，比如說，用與BRACELET 中使用的不同的檢查點評估pela - 1？

Excellent question. Thanks. Yeah, we do believe that. And again, for people looking at the story, at ESMO what we presented was a tripling of the objective response rate when we added pela to paclitaxel, a 50% increase in the median overall survival. And then we're tracking for overall survival. The hazard ratio is 0.29, so it's really quite a remarkable improvement.

很好的問題。謝謝。是的，我們確實相信這一點。再說一次，對於那些看過這個故事的人來說，在 ESMO 上，我們展示的是，當我們在紫杉醇中添加 pela 時，客觀緩解率增加了三倍，中位總生存期增加了 50%。然後我們追蹤總體生存率。風險比為 0.29，所以這確實是一個相當顯著的改進。

When we added avelumab, it eliminated that benefit. And what we've found out since and subsequently avelumab is the owner only approved checkpoint inhibitor with a non-modified Fc portion. So for anyone not familiar, the Fc portion on an antibody, so an antibody basically looks like the letter Y or a wrench. The part that would engage with the bolt is the Fab portion, the portion that changes and finds the epitope and allows you to have a selective antibody response against the specific epitope. The handle of the wrench interacts with other immune cells through MHC molecules.

當我們添加 avelumab 時，它消除了這種好處。我們隨後發現 avelumab 是所有者唯一批准的具有未修飾 Fc 部分的檢查點抑制劑。對於任何不熟悉的人來說，抗體上的 Fc 部分，因此抗體基本上看起來像字母 Y 或扳手。與螺栓接合的部分是 Fab 部分，該部分會改變並找到表位，並允許您對特定表位產生選擇性抗體反應。扳手的手柄透過 MHC 分子與其他免疫細胞相互作用。

Every other developer on the planet has silence that Fc portion so that it doesn't engage with macrophage. And the reason for that as it can lead to T-cell engulfment or macrophage engulfment as a T-cell. So as oppose to expanding a T-cell response, it'll actually collapse it. And there's actually publications and literature talking about how avelumab treatment can actually lead to hyperproliferation, that's to say there will actually be tumors grow faster.

地球上所有其他開發者都沉默了 Fc 部分，這樣它就不會與巨噬細胞結合。原因是它可以導致 T 細胞吞噬或巨噬細胞吞噬為 T 細胞。因此，與擴大 T 細胞反應相反，它實際上會破壞它。實際上有出版物和文獻談論 avelumab 治療實際上如何導致過度增殖，也就是說腫瘤實際上會生長得更快。

So it was a poor choice to combine with an agent like ours that relies on a T-cell response. And you can see this from our TCR sequencing. The addition of avelumab caused T-cell collapse.

因此，與我們這樣依賴 T 細胞反應的藥物合併使用是一個糟糕的選擇。您可以從我們的 TCR 定序中看到這一點。加入 avelumab 導致 T 細胞崩潰。

When we spoke with partners about this, they said that was unexpected outcome based on this non-silenced Fc portion. So we still think breast cancer can benefit from the addition of a checkpoint inhibitor and especially something like atezolizumab where it is directed against the PD-L1 (technical difficulty) moiety rather than the PD-1. And that's just to say, for us, it's better because they've got an expression on the tumor cells itself. So we can actually direct to where we want to direct.

當我們與合作夥伴討論這個問題時，他們表示，基於非沉默 Fc 部分，這是意想不到的結果。因此，我們仍然認為乳癌可以從添加檢查點抑制劑中受益，尤其是像 atezolizumab 這樣的藥物，它針對的是 PD-L1（技術難度）部分而不是 PD-1。這只是說，對我們來說，更好，因為它們在腫瘤細胞本身上有表達。所以我們實際上可以引導到我們想要引導的地方。

So it should work with durva, atezolizumab, but we've seen synergy with other PD-L1s that have non -- that have silenced Fc portions like Merck. I'm just -- with the growing body of evidence, the atezolizumab is looking really good in terms of the underlying synergies.

所以它應該與 durva、atezolizumab 一起使用，但我們已經看到與其他不具有沉默 Fc 部分（如默克）的 PD-L1 的協同作用。我只是——隨著越來越多的證據，阿特珠單抗在潛在的協同作用方面看起來非常好。

Yes, I think we should be looking at this in the breast cancer space. And I think that becomes an important component of our lifecycle management. For a couple of reasons, I think we'll be successful with just paclitaxel, pela. Two randomized studies, I'm very comfortable thinking that a third study is going to be as successful as the last two. But the question is, can we make it even better? Can we get -- to treat responses even better survival, more objective response? So I think it makes sense to study that. But Phase 3 is not going to look at that, that will be more of a lifecycle management aspect.

是的，我認為我們應該在乳癌領域中關注這一點。我認為這成為我們生命週期管理的重要組成部分。基於幾個原因，我認為我們只使用紫杉醇、佩拉就能取得成功。兩項隨機研究，我很高興地認為第三項研究將與前兩項研究一樣成功。但問題是，我們能做得更好嗎？我們能否獲得更好的存活率、更客觀的治療反應？所以我認為研究這個是有意義的。但第三階段不會考慮這一點，這將更涉及生命週期管理方面。

And then the question is reimbursement. Pela combination will be priced like any other immunological therapy. If we add a checkpoint inhibitor that will double that number again, so the question of how much benefit do we have to see to ensure reimbursement of a drug combination that could be looking between $300,000 and $400,000 conservatively.

然後問題就是報銷。 Pela 組合的定價將與任何其他免疫療法一樣。如果我們添加一種檢查點抑制劑，這個數字會再次翻倍，那麼問題是我們必須看到多少好處才能確保藥物組合的報銷，保守地說可能在 30 萬美元到 40 萬美元之間。

So it is a question we have to answer, but it will be answered as we're running the Phase 3 program, so that we can say, okay, let's get the approval. Here's the next steps, but I agree with you wholeheartedly. The avelumab, unfortunately, was a poor choice and I don't think is reflective of the underlying synergy we see with other checkpoint inhibitors, and it is something we can study.

所以這是一個我們必須回答的問題，但是當我們運行第三階段計劃時就會得到答案，這樣我們就可以說，好吧，讓我們獲得批准。這是接下來的步驟，但我完全同意你的觀點。不幸的是，avelumab 是一個糟糕的選擇，我認為它不能反映我們與其他檢查點抑制劑所看到的潛在協同作用，這是我們可以研究的東西。

And it was interesting. We just had a Board meeting yesterday and the clinical component of our discussion work as we're running the Phase 3, where can we get other studies with cooperative groups like PanCAN, URTC, NCI, NCIC to really start bolstering studies into other pivotal indication. And obviously checkpoint inhibitor is going to figure very largely and that's a picture.

這很有趣。我們昨天剛召開了一次董事會會議，討論了我們正在進行第3 階段工作的臨床部分，我們可以在哪裡與PanCAN、URTC、NCI、NCIC 等合作團體進行其他研究，以真正開始支持其他關鍵適應症的研究。顯然，檢查點抑制劑將發揮很大作用，這就是圖片。

Great. Yeah. Thanks for the detailed answer there and taking the question and congrats again on all the progress.

偉大的。是的。感謝您的詳細回答並提出問題，並再次祝賀所有進展。

That is our last question. I'd now like to turn the call back over to Mr. Matt Coffey for any closing remarks.

這是我們的最後一個問題。現在，我想將電話轉回給馬特·科菲先生，讓他作結束語。

Thank you for that. Thank you, everyone, who turned into hear about our progress. The data presented at ESMO and pancreatic and colorectal cancer in addition to our AWARE-1 abstract data presented at SITC reinforce the ability of pela to remodel tumor microenvironment and generate an immune responses in patients, even in those with immune systems diminished by previous lines of therapy.

謝謝你。謝謝大家，誰來聽我們的進展。在ESMO 和胰腺癌和結直腸癌上提供的數據以及我們在SITC 上提供的AWARE-1 摘要數據增強了Pela 重塑腫瘤微環境並在患者中產生免疫反應的能力，即使是那些免疫系統因先前的治療線而減弱的患者治療。

The data also adds the portfolio of evidence that pela synergizes with checkpoint inhibitors like atezolizumab. We will continue to advance towards licensure-enabling studies in breast and pancreatic cancer and provide additional updates on our progress.

這些數據還增加了 pela 與 atezolizumab 等檢查點抑制劑具有協同作用的證據組合。我們將繼續推進乳腺癌和胰腺癌的許可研究，並提供有關我們進展的更多最新資訊。

With that, I wish everyone a wonderful rest of your day. Thanks again, everyone, and appreciate it.

在此，我祝福大家有個愉快的一天。再次感謝大家，並表達感謝。

Thank you, sir. Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines. Have a lovely day.

謝謝你，先生。女士們、先生們，今天的電話會議到此結束。我們感謝您的參與，並請您斷開線路。祝你愉快。