Agenus Inc (AGEN) 2024 Q2 法說會逐字稿

Good morning and welcome to Agenus second quarter 2024 conference call and webcast. All participants will be in a listen-only mode until the question-and-answer session. Please note, this event is being recorded. If anyone has any objections, you may disconnect at this time.

早安，歡迎來到 Agenus 2024 年第二季電話會議和網路廣播。在問答環節之前，所有參與者都將處於只聽模式。請注意，此事件正在被記錄。如果有人有任何異議，您可以此時斷開連接。

(Operator instructions) I would now like to turn the call over to Zack Armen, Head of Investor Relations at Agenus. Zack, please go ahead.

（操作員指示）我現在想將電話轉給 Agenus 投資者關係主管 Zack Armen。扎克，請繼續。

Thank you, Leonardo, and thank you all for joining us today. Today's call is being webcast and will be available on our website for replay. I'd like to remind you that this call will include forward-looking statements, including statements regarding our clinical development, regulatory and commercial plans and timelines, as well as timelines for data release and partnership opportunities among other updates.

謝謝你，萊昂納多，也謝謝大家今天加入我們。今天的電話會議正在進行網路直播，並將在我們的網站上重播。我想提醒您，本次電話會議將包括前瞻性聲明，包括有關我們的臨床開發、監管和商業計劃和時間表的聲明，以及數據發布和合作機會等更新的時間表。

These statements are subjects to risks and uncertainties, and we refer you to our SEC filings available on our website for more details on these risks.

這些聲明存在風險和不確定性，我們建議您參閱我們網站上提供的 SEC 文件，以了解有關這些風險的更多詳細資訊。

Joining me today are Dr. Garo Armen, Chairman and Chief Executive Officer; Dr. Steven O'Day, Chief Medical Officer; and Christine Klaskin, Vice President of Finance. Dr. Robin Taylor, Chief Commercial Officer will be participating in the Q&A session.

今天與我一起出席的有董事長兼執行長 Garo Armen 博士； Steven O'Day 博士，首席醫療官；克里斯汀‧克拉斯金 (Christine Klaskin)，財務副總裁。商務長 Robin Taylor 博士將參加問答環節。

Now, I'd like to turn the call over to Garo to highlight our progress in the second quarter. Garo?

現在，我想將電話轉給加羅，以強調我們在第二季度的進展。加羅？

Good morning, everyone and thank you for joining us today. On the merits of our circumstances and on matters within our control, with a strong emphasis on impacting patient lives, we have made significant progress in the development of botensilimab, which we call BOT, and balstilimab, which we call BAL. And these are for the treatment of colorectal cancer, even though the combination has been used for many other cancers.

大家早安，感謝您今天加入我們。根據我們的情況和我們控制範圍內的事情，我們非常重視影響患者的生活，我們在博替利單抗（我們稱之為BOT）和巴斯蒂利單抗（我們稱之為BAL）的開發方面取得了重大進展。這些藥物用於治療大腸直腸癌，儘管該組合已用於治療許多其他癌症。

Recently, Agenus disclosed top-line data from its global Phase 2 trial, evaluating the BOT/BAL combination in patients with relapsed refractory microsatellite stable, which is called MSS colorectal cancer. These patients constitute about 95% of the diagnosed colorectal cancer patients globally, and as you know, colorectal cancer has been on a significant rise as of late.

最近，Agenus 揭露了其全球 2 期試驗的主要數據，該試驗評估了 BOT/BAL 組合治療復發難治性微衛星穩定（稱為 MSS 結直腸癌）患者的效果。這些患者約佔全球確診大腸直腸癌患者的 95%，而且如您所知，大腸直腸癌近年來呈顯著上升趨勢。

The results from our second trial, the Phase 2 trial, are consistent with those observed in our Phase 1 trial, demonstrating a confirmed overall response rate of approximately 20% in the cohorts receiving 75 milligrams of BOT plus 240 milligrams of BAL combination. This dosage has been identified as the active dose during a recent meeting with the US FDA, allowing Agenus to proceed with further development, including our planned confirmatory Phase 3 trial.

我們的第二項試驗（2 期試驗）的結果與我們在 1 期試驗中觀察到的結果一致，顯示接受 75 毫克 BOT 加 240 毫克 BAL 組合的隊列中確認的總體緩解率約為 20%。在最近與美國 FDA 的一次會議上，該劑量已被確定為活性劑量，使 Agenus 能夠繼續進一步開發，包括我們計劃的驗證性 3 期試驗。

BOT/BAL is demonstrating unprecedented activity in treating challenging cancers across various stages, both as a chemotherapy-free, IO-IO only combination, as well as in combination with standard chemotherapy in first-line metastatic patients where chemotherapy is the standard of care.

BOT/BAL 在治療各個階段的挑戰性癌症方面表現出前所未有的活性，無論是作為無化療、僅 IO-IO 的組合，還是與標準化療聯合治療以化療為標準治療的一線轉移性患者。

It is important to recognize that key opinion leaders and clinical investigators globally, including significant numbers in the US who have seen our data and/or have experienced the outcomes in their patients, strongly advocate making BOT/BAL available to their patients.

重要的是要認識到，全球的關鍵意見領袖和臨床研究人員，包括在美國看到我們的數據和/或在患者身上體驗過結果的大量人員，強烈主張為患者提供 BOT/BAL。

In our trials of significant numbers of patients suffering more than 350 in colorectal cancer and over 1,000 patients across 10 different cancer types, we are seeing deep, durable responses in patients who otherwise face grim prognosis with current standard treatment. We believe, along with the experts in the field, that these durable responses translate to long-term patient benefit.

在我們對超過 350 名結直腸癌患者和超過 1,000 名 10 種不同癌症類型的患者進行的試驗中，我們發現，使用當前標準治療可能面臨嚴峻預後的患者獲得了深度、持久的緩解。我們與該領域的專家一起相信，這些持久的反應可以轉化為患者的長期利益。

While the FDA has not yet concurred with this view, and the urgency to make BOT/BAL widely available to patients and their treating physicians, we are optimistic that our mature data will influence their thinking. On the other hand, we're very encouraged with the initial feedback from other regulatory agencies, which has been notably much more positive thus far.

雖然 FDA 尚未同意這一觀點，也不同意將 BOT/BAL 廣泛提供給患者及其治療醫生的緊迫性，但我們樂觀地認為，我們的成熟數據將影響他們的想法。另一方面，我們對其他監管機構的初步回饋感到非常鼓舞，到目前為止，這些回饋明顯更加正面。

On this note, we started engaging with regulatory bodies outside of the US, including the European Agency, in order to explore rapid approval pathways for BOT/BAL. In Europe, this could mean conditional approval to bring these potentially life-saving agents to patients as soon as possible.

為此，我們開始與美國以外的監管機構（包括歐洲機構）合作，以探索 BOT/BAL 的快速批准途徑。在歐洲，這可能意味著有條件批准盡快將這些可能挽救生命的藥物帶給患者。

Separately from all of this, we are very excited to share that important and very exciting data from a multi-cancer neoadjuvant study, which is being conducted at a major European cancer center, will be presented at a major cancer conference in upcoming months.

除此之外，我們非常高興地分享來自歐洲一家主要癌症中心正在進行的多癌症新輔助研究的重要且非常令人興奮的數據，該研究將在未來幾個月的大型癌症會議上公佈。

Our clinical data, as you know, has generated strong support from medical and scientific communities. Recent publications in Nature Medicine and Cancer Discovery, along with a peer-reviewed journal article that came in from Dana-Farber Cancer Institute here in Boston, emphasize the importance of bringing BOT/BAL to patients with MSS colorectal cancer.

如您所知，我們的臨床數據得到了醫學界和科學界的大力支持。最近在《Nature Medicine》和《Cancer Discovery》上發表的文章，以及波士頓Dana-Farber 癌症研究所發表的一篇同行評審的期刊文章，都強調了將BOT/BAL 應用於MSS 結直腸癌患者的重要性。

By the way, MSS colorectal cancer is one of the most difficult cancers to treat, not just within the colorectal realm, but across the Board. We've also seen an unprecedented number of compassionate use requests, driven by the deep and durable responses in a cancer where patients have no acceptable options among many approved drugs, highlighting the urgent demand for BOT/BAL in the colorectal cancer community. Dr. O'Day will describe this reality in more detail during our call.

順便說一句，MSS 結直腸癌是最難治療的癌症之一，不僅在結直腸領域，而且在整個範圍內都是最難治療的。我們也看到了前所未有的數量的同情使用請求，這是由於癌症的深刻而持久的反應所驅動的，患者在許多批准的藥物中沒有可接受的選擇，這突顯了結直腸癌社區對BOT/BAL 的迫切需求。奧戴博士將在我們的電話會議中更詳細地描述這一現實。

On the business side, we're actively exploring global partnerships for BOT/BAL and other assets in our pipeline. We've regained full rights to AGEN1777 and AGEN2373 from BMS and Gilead, respectively, and are evaluating new partnerships for these programs among the biopharma industry players. As you know, many companies out there are scrambling to cut costs, and I'm talking about large companies, medium-sized companies, and small companies. But there are still pockets of brilliance among them.

在業務方面，我們正在積極探索 BOT/BAL 以及我們管道中的其他資產的全球合作夥伴關係。我們已分別從 BMS 和吉利德獲得 AGEN1777 和 AGEN2373 的全部權利，並正在評估生物製藥行業參與者之間針對這些項目的新合作夥伴關係。大家知道，很多公司都在爭先恐後地削減成本，我說的是大公司、中型公司和小公司。但他們之中仍然不乏閃光點。

Interestingly, we've been having increased interest from some of these innovative companies following our announcement about the FDA guidance discouraging accelerated filing. We've strengthened our cash position in the second quarter with the first transfer of the $75 million royalty financing led by Ligand Pharmaceuticals, and we're in talks with investors for a second closing.

有趣的是，在我們宣布 FDA 不鼓勵加速申請的指導意見後，一些創新公司對我們的興趣不斷增加。透過首次轉讓由 Ligand Pharmaceuticals 牽頭的 7,500 萬美元特許權使用費融資，我們在第二季度加強了現金狀況，並且我們正在與投資者就第二次交割進行談判。

We're encouraged by the fact that we have received inquiries to potentially invest at premium prices to our current stock price. Additionally, I'd like to let you know ahead of time, because the filing will be this afternoon, that we will be expanding our ATM filing facility to be in a state of readiness, in spite of the fact that we have no current plans to issuing stock at these prices. And you will see in this filing that we've done some minor sales in the first half of the year, but the average price has been approximately $15 a share.

我們收到了可能以高於當前股價的溢價進行投資的詢盤，這一事實令我們感到鼓舞。此外，我想提前通知您，因為備案將於今天下午進行，我們將擴大 ATM 備案設施以使其處於就緒狀態，儘管我們目前沒有計劃以這些價格發行股票。您會在這份文件中看到，我們在今年上半年進行了一些小額銷售，但平均價格約為每股 15 美元。

Given the uniquely active nature of our agents, our commitment to advancing BOT/BAL is stronger than ever before. We're dedicated to ensuring that patients get access to these lifesaving therapies as quickly as possible. And you will hear about some of the plans that we're contemplating on putting into place as soon as possible from my colleagues later on.

鑑於我們代理商獨特的活躍性質，我們對推動 BOT/BAL 的承諾比以往任何時候都更加堅定。我們致力於確保患者盡快獲得這些挽救生命的療法。稍後您會從我的同事那裡聽到我們正在考慮盡快實施的一些計劃。

Before we hear from Dr. O'Day about more details on our patient-centric, exciting and life-altering outcomes, I'm delighted to announce that Tom Harrison has joined our Board of Directors. A few words about Tom before I introduce him. Tom is one of the true transformative leaders in the healthcare industry, having grown diversified agency services into Omnicom Group's largest division with over 5,000 clients and annual revenues exceeding $6 billion.

在我們聽到 O'Day 博士關於我們以患者為中心、令人興奮和改變生活的成果的更多細節之前，我很高興地宣布湯姆·哈里森 (Tom Harrison) 已加入我們的董事會。在介紹湯姆之前先簡單介紹一下他。Tom 是醫療保健行業真正的變革型領導者之一，他將多元化的代理服務發展成為 Omnicom 集團最大的部門，擁有超過 5,000 名客戶，年收入超過 60 億美元。

His deep experience in healthcare communications and branding, combined with a strong scientific background from his early days at Pfizer, makes him very uniquely equipped to guide Agenus in our next phase of growth.

他在醫療保健傳播和品牌推廣方面的豐富經驗，加上他早期在輝瑞公司的強大科學背景，使他非常有能力指導 Agenus 下一階段的發展。

Tom's innovative approach in merging high science with creative marketing will be key in our ability to educate the global community about the critical benefits of our therapy. I want to emphasize educating. His strategic vision and operational experience is key in our efforts to bring groundbreaking cancer treatments to patients worldwide, not just the US.

湯姆將高科技與創意行銷結合的創新方法將是我們向全球社區宣傳我們療法的關鍵益處的能力的關鍵。我想強調的是教育。他的策略願景和營運經驗對於我們為全世界（而不僅僅是美國）患者提供突破性癌症治療的努力至關重要。

Please join me in welcoming Tom Harrison to say a few words on this call. Tom?

請和我一起歡迎湯姆·哈里森在這次電話會議上發言。湯姆？

Thank you so much for that. Most kind introduction. Hopefully, I'm worthy of those wonderful words. I'm truly honored to join the Board of Directors of Agenus, a company that is at the forefront of innovation in the field of immuno-oncology. The work that is being done here at Agenus is not only groundbreaking, but it's also life changing for patients battling some of the most challenging cancers that Garo has already outlined on the call.

非常感謝你。最親切的介紹。希望我配得上這些美妙的話語。我非常榮幸能夠加入 Agenus 的董事會，Agenus 是一家處於免疫腫瘤學領域創新前沿的公司。Agenus 正在進行的工作不僅具有開創性，而且還改變了加羅在電話會議上概述的一些最具挑戰性癌症的患者的生活。

As someone who has spent a significant portion of my career in healthcare advertising and strategic advising of CEOs across the healthcare industry, I'm excited to bring my experience to Agenus. The opportunity to help elevate the awareness of our innovative pipeline and to communicate the significant advances that we are making in cancer treatment is something that I am really deeply passionate about.

作為一個在醫療保健廣告和整個醫療保健行業的執行長策略諮詢方面度過了職業生涯的重要部分的人，我很高興將我的經驗帶到 Agenus。我非常熱衷於有機會幫助提高我們創新管道的意識並傳達我們在癌症治療方面取得的重大進展。

My career, as Garo said, has always been driven by a commitment to excellence and innovation founded on a basis of science. From co-founding Harrison and Star Business Group to my current role as Senior Operating Partner at Merida Capital Partners, I have been fortunate to work throughout my career with very talented teams, such as the one here at Agenus, and to drive growth and deliver impactful results. I see a similar spirit of innovation and dedication here at Agenus, and I am eager to contribute to our shared mission.

正如加羅所說，我的職業生涯始終受到以科學為基礎的卓越和創新的承諾的推動。從聯合創始人 Harrison 和 Star Business Group 到目前擔任 Merida Capital Partners 的高級營運合夥人，我很幸運在整個職業生涯中與非常有才華的團隊（例如 Agenus 的團隊）一起工作，並推動成長並交付成果有影響力的結果。我在 Agenus 看到了類似的創新和奉獻精神，我渴望為我們的共同使命做出貢獻。

One of my key priorities, as Garo said, will be to enhance our strategic communications efforts to ensure that our scientific advancements and our therapeutic potential are clearly understood by healthcare providers, by patients, by investors, and regulatory bodies around the world.

正如加羅所說，我的首要任務之一是加強我們的策略溝通工作，以確保世界各地的醫療保健提供者、患者、投資者和監管機構清楚地了解我們的科學進步和治療潛力。

By doing so, we can not only elevate the visibility and reputation of Agenus, but also help accelerate the delivery of our lifesaving therapies to those who are in dire need. I am particularly excited about the progress we are making with our BOT/BAL program and the potential it holds to address unmet medical needs across multiple cancer indications.

透過這樣做，我們不僅可以提高 Agenus 的知名度和聲譽，還可以幫助加速向那些急需的人提供我們的救生療法。我對 BOT/BAL 計劃所取得的進展及其解決多種癌症適應症中未滿足的醫療需求的潛力感到特別興奮。

The robust data that we have generated, coupled with our active engagements with global regulatory authorities, positions us well to bring these innovative treatments to market. I look forward to working closely with Garo, with the full Board of Directors, and the entire senior Agenus team to drive our mission forward.

我們產生的可靠數據，加上我們與全球監管機構的積極合作，使我們能夠將這些創新療法推向市場。我期待與 Garo、整個董事會以及整個 Agenus 高級團隊密切合作，推動我們的使命向前發展。

Together, we will continue to push our boundaries of what is possible in cancer immunotherapy and improve patient outcomes. Thank you again, Garo, for the warm welcome, and everyone for the warm welcome with whom I've spoken, and I'm excited about the journey that we have ahead.

我們將共同努力，繼續突破癌症免疫治療的極限，並改善患者的治療效果。加羅，再次感謝您的熱情歡迎，以及與我交談過的所有人的熱情歡迎，我對我們接下來的旅程感到興奮。

So now I'm going to turn the call over to Steven to go over our updates of our clinical progress to date.

所以現在我要把電話轉給史蒂文，回顧我們迄今為止的臨床進展的最新情況。

Thank you, Tom and Garo. I'm pleased to provide an update on our clinical progress across the BOT/BAL program now, as Garo said, spanning over 1,100 patients treated in refractory advanced cancers, as well as earlier stages of metastatic disease, and most recently in the neoadjuvant setting.

謝謝你們，湯姆和加羅。正如Garo 所說，我很高興現在提供有關BOT/BAL 計畫臨床進展的最新信息，該計畫涵蓋1,100 多名接受難治性晚期癌症以及轉移性疾病早期階段治療的患者，以及最近在新輔助治療中的患者。

BOT/BAL is demonstrating remarkable activity, with a manageable safety profile in patients with relapsed refractory MS-stable colorectal cancer and non-active liver metastatic disease. Our data remains consistent between the Phase 1 expanded cohort and our Phase 2 randomized trials, particularly in terms of RECIST-confirmed overall response rates, duration of response, and importantly, overall survival.

BOT/BAL 在復發難治性 MS 穩定大腸直腸癌和非活動性肝轉移性疾病患者中表現出顯著的活性，且安全性可控。我們的 1 期擴展隊列數據與 2 期隨機試驗之間的數據保持一致，特別是在 RECIST 確認的總體緩解率、緩解持續時間以及重要的總體生存率方面。

Our (technical difficulty) MS-stable colorectal cancer patient population of 23% in the Phase 1 trial and now 19.4% in Phase 2 trial (technical difficulty) is roughly three times the low single-digit overall response rate of any available standard of care therapy in this setting.

我們的（技術難度）多發性硬化症穩定大腸直腸癌患者群體在1 期試驗中佔23%，現在在2 期試驗（技術難度）中佔19.4%，大約是任何現有護理標準的低個位數總體緩解率的三倍在這種情況下進行治療。

Our median overall survival for the Phase 1 trial of 21.2 months, with a remarkable 18-month estimated overall survival of 63%, stands in marked contrast to approximately, at best, 12 months with the best standard of care therapies.

我們的 1 期試驗的中位總存活期為 21.2 個月，18 個月的估計總存活期高達 63%，與最佳標準護理治療的約 12 個月形成鮮明對比。

While survival with the Phase 2 dataset is early and maturing, we see consistency in the six-month survival rate of 90% in our selected combination BOT/BAL arm in the Phase 2 trial, as compared with the 88% in the Phase 1 BOT/BAL arms, and this is very reassuring to us. We plan to submit the Phase 2 data after a later maturity data cut later this year to a major medical congress in the early part of 2025.

雖然2 期資料集的生存率還處於早期階段並且正在成熟，但我們在2 期試驗中選擇的BOT/BAL 組合組中，六個月的生存率為90%，而1 期BOT 的生存率為88%，這是一致的/BAL 武器，這讓我們非常放心。我們計劃在今年稍後將成熟度數據削減後的第 2 階段數據提交給 2025 年初的大型醫學大會。

We are confident that as these data mature, they will continue to demonstrate differentiation in overall response, duration response, and survival compared to standard of care therapies in this late-line refractory MS-stable colorectal cancer.

我們相信，隨著這些數據的成熟，與這種晚期難治性多發性硬化症穩定結直腸癌的標準護理療法相比，它們將繼續證明在整體反應、持續時間反應和生存方面存在差異。

In addition, we are seeing remarkable activity of BOT/BAL in earlier stages of CRC treatment lines, which is highlighted by our data in the NEST neoadjuvants trial, which was updated with an oral presentation at ESMO GI in Munich in this past June.

此外，我們還看到BOT/BAL 在CRC 治療線早期階段的顯著活性，我們在NEST 新佐劑試驗中的數據突顯了這一點，該試驗於今年6 月在慕尼黑ESMO GI 上進行了口頭報告更新。

This trial evaluated one dose of BOT with two to four doses of BAL before surgery. In the updated NEST-2 cohort, which provided longer time between the first dose of BOT/BAL and surgery of up to eight weeks, remarkably seven of nine MS-stable colorectal patients, or 78%, achieved at least a 50% tumor regression at the time of surgery, with five out of nine or 56% achieving complete pathologic regressions of their tumors.

該試驗在手術前評估了一劑 BOT 和兩到四劑 BAL。在更新的NEST-2 隊列中，首次注射BOT/BAL 和手術之間的時間長達八週，顯著地，九名MS 穩定的結直腸患者中有七名（即78%）實現了至少50%的腫瘤消退在手術時，九分之五（即 56%）的腫瘤實現了完全病理消退。

Importantly, no surgeries were delayed due to adverse events. This data stands in stark contrast to historical data with attempts at neoadjuvant IO therapy in poorly immunogenic MS-stable colorectal cancer where pathologic response rates have been poor.

重要的是，沒有任何手術因不良事件而延誤。這項數據與在免疫原性差的 MS 穩定結直腸癌中嘗試新輔助 IO 治療的歷史數據形成鮮明對比，這些癌症的病理反應率一直很差。

We plan to continue to build on these groundbreaking data in the neoadjuvant setting with additional studies, as Garo alluded to, and additional IST studies are ongoing. Data in our Phase 2 BOT/BAL melanoma and pancreas trials continue to mature, and we look forward to updating these data in the coming months.

正如 Garo 所提到的那樣，我們計劃繼續在新輔助治療中以這些突破性數據為基礎，進行更多研究，並且其他 IST 研究正在進行中。我們的 2 期 BOT/BAL 黑色素瘤和胰臟試驗數據不斷成熟，我們期待在未來幾個月內更新這些數據。

Finally, we will be presenting updated data with BOT and BAL in a relapsed/refractory sarcoma population in an oral presentation at the ESMO conference in Barcelona in September.

最後，我們將在 9 月於巴塞隆納舉行的 ESMO 會議上進行口頭報告，介紹 BOT 和 BAL 在復發/難治性肉瘤人群中的最新數據。

Now, I'll turn the call over to Christine to review our financials.

現在，我將把電話轉給克里斯汀，讓她審查我們的財務狀況。

Thank you, Steven. We ended the second quarter 2024 with a consolidated cash balance of $93.7 million, compared to $76.1 million on December 31, 2023. For the three and six-months ended June 30, 2024, we recognized revenues which includes (technical difficulty) of $23.5 million and $51.5 million respectively. This compares to $25.3 million and $48.2 million for the same period in 2023.

謝謝你，史蒂文。截至 2024 年第二季末，我們的綜合現金餘額為 9,370 萬美元，而 2023 年 12 月 31 日為 7,610 萬美元。截至 2024 年 6 月 30 日的三個月和六個月，我們確認的收入分別為 2,350 萬美元和 5,150 萬美元，其中包括（技術難度）。相較之下，2023 年同期為 2,530 萬美元和 4,820 萬美元。

Our cash used in operations for the first half of 2024 was $76.4 million, a reduction from $118.6 million for the first half of 2023. Our net loss for the three and six-month ended June 30, 2024, it's $54.8 million and $118.3 million. These include non-cash operating expenses of $33.5 million and $71.8 million, respectively. I will now turn the call back to closing remarks.

2024 年上半年我們營運中使用的現金為 7,640 萬美元，較 2023 年上半年的 1.186 億美元有所減少。截至 2024 年 6 月 30 日的三個月和六個月的淨虧損分別為 5,480 萬美元和 1.183 億美元。其中包括分別為 3,350 萬美元和 7,180 萬美元的非現金營運費用。我現在將在電話會議上致閉幕詞。

Thank you very much, Tom, Steven, and Christine. I'd like to extend my gratitude to everyone for joining us today to review our second quarter progress. Our unwavering focus remains on delivering BOT/BAL to individuals living with advanced MSS colorectal cancer and many other cancers where we have shown activity. We are steadfastly exploring innovative and expedited methods to make these treatment options available worldwide.

非常感謝湯姆、史蒂文和克莉絲汀。我要感謝大家今天加入我們回顧我們第二季的進展。我們堅定不移的重點仍然是為患有晚期 MSS 結直腸癌和我們已表現出活動的許多其他癌症的患者提供 BOT/BAL。我們正在堅定不移地探索創新和快速的方法，以使這些治療方案在全世界範圍內可用。

Remember, amongst the importance of these treatment options is that they represent IO-IO, that is immuno-oncology, immuno-oncology combo treatments, without chemotherapy, with an extended life extension potential. This is very important for patients that have absolutely no options going forward with limited benefit and horrible toxicity.

請記住，這些治療方案的重要性之一是它們代表 IO-IO，即免疫腫瘤學、免疫腫瘤學組合治療，無需化療，具有延長壽命的潛力。這對於那些完全沒有選擇且獲益有限且毒性可怕的患者來說非常重要。

Patients are counting on us, and we are deeply committed to fulfilling our mission to provide therapies with curative intent, not only for colorectal cancer, but as I said, for many other cancer types where we have seen some profound activity. Thank you very much for your continued support and trust in Agenus.

患者指望我們，我們堅定地致力於履行我們的使命，提供具有治癒目的的療法，不僅針對結直腸癌，而且正如我所說，針對許多其他癌症類型，我們已經看到了一些深刻的活動。非常感謝您一直以來對Agenus的支持與信任。

I will now turn the call back to the Operator to facilitate any questions you may have. Operator?

我現在將把電話轉回給接線員，以解答您可能遇到的任何問題。操作員？

Thank you. (Operator instructions) Emily Bodnar, HC Wainwright.

謝謝。（操作員說明）Emily Bodnar，HC Wainwright。

Thanks for taking my questions. My first one is can you again discuss the FDA's guidance for the Phase 3 design in terms of the number of patients that you might need per arm, including the center of care arm and specific end points that you plan to look at?

感謝您回答我的問題。我的第一個問題是，您能否再次討論 FDA 對 3 期設計的指導，即每個臂可能需要的患者數量，包括護理臂的中心和您計劃關注的具體終點？

And then, maybe if you can give any guidance to how soon you believe you could initiate a Phase 3 study and whether you believe the resources you have financially could support you running one along? Thanks.

然後，也許您可以就您認為多久可以啟動第 3 階段研究以及您是否認為您擁有的財務資源可以支持您開展一項研究提供任何指導？謝謝。

So Emily, among the options that we're considering right now is a Phase 3 trial that can commence as early as the next four months and enroll inside of a year. And the reason I say enroll inside of a year is because there is such outcry of patient demand out there that we're getting, and this has been at an increasing pace before the FDA guidance was issued, which we announced a couple weeks ago, and particularly after the FDA guidance because now patients are very concerned that they're not going to be able to get this drug in a commercial setting.

Emily，我們現在正在考慮的選項之一是第三階段試驗，最早可以在接下來的四個月內開始，並在一年內註冊。我說在一年內註冊的原因是因為我們收到了患者需求的強烈抗議，在我們幾週前宣布的 FDA 指南發布之前，這種需求一直在不斷增加，尤其是在FDA 指導之後，因為現在患者非常擔心他們無法在商業環境中獲得這種藥物。

And so, there is a huge interest of patients coming to us for drugs globally. So that's why we believe that once we initiate a Phase 3 trial, we'll be able to enroll very rapidly. That's why I feel confident that enrolling patients inside of a year post-commencement is something that is highly possible. Now, among the options that we are considering for Phase 3 trial we've been approached by certain groups that has significant subsidies offered to bring innovative medicines to patients as soon as possible.

因此，全球患者對我們尋求藥物表現出極大的興趣。因此，我們相信一旦啟動第三階段試驗，我們將能夠非常迅速地註冊。這就是為什麼我相信在啟動後一年內招募患者是很有可能的。現在，在我們正在考慮的第三階段試驗的選項中，某些團體已經與我們接洽，這些團體提供了大量補貼，以盡快為患者提供創新藥物。

Among these groups is an outfit that has proposed to do a randomized Phase 3 trial that will satisfy the needs of regulatory agencies globally, not just the FDA, for as little as $10 million. So that's what we're really exploring now among other options, and stay tuned, the decision will be made in the couple of months.

這些組織中的一個機構提議進行一項隨機 3 期試驗，該試驗將滿足全球監管機構（而不僅僅是 FDA）的需求，只需 1000 萬美元。這就是我們現在真正在其他選擇中探索的內容，請繼續關注，我們將在幾個月內做出決定。

Okay. Great. Thank you. And I believe you mentioned that you're expecting to have data in pancreatic and melanoma cancers in the coming months. Could you just confirm if that's expected for this year and if so, how much data should really be expecting?

好的。偉大的。謝謝。我相信您提到您預計在未來幾個月內獲得胰腺癌和黑色素瘤的數據。您能否確認一下今年是否會出現這種情況？

So we are expecting maturing data to be disclosed in pancreatic cancer and melanoma, in lung cancer and neoadjuvant cancer patients of all comers, which is a trial that I spoke about which is being conducted at a major cancer center in Europe by a very, very difficult investigator who's had experience with other neoadjuvant trials. So these are among the most important data outputs that you will see in coming months.

因此，我們期待在胰腺癌和黑色素瘤、肺癌和所有新輔助癌症患者中披露成熟的數據，這是我談到的一項試驗，該試驗正在歐洲的一個主要癌症中心進行，由一個非常非常具有其他新輔助試驗經驗的困難研究者。因此，這些是您在未來幾個月將看到的最重要的數據輸出。

Kelly Shi, Jefferies.

施凱莉，傑弗里斯。

Hi. Good morning. This is Claire on for Kelly. Thanks for taking our question.

你好。早安.這是克萊爾為凱利代言的。感謝您提出我們的問題。

It's very difficult to hear you. Very difficult to hear you.

很難聽到你的聲音。很難聽到你的聲音。

Can you hear me now?

現在你能聽到我說話嗎？

Yeah, better.

是的，更好了。

Okay. Great. This is Claire on for Kelly. Thanks for taking our question. So wondering if you could provide more color on the initial meeting you had with the European agency. What kind of data did you show them and whether that's the same data package as what you provided to the FDA? And for the subsequent meetings could you let us know what would the key discussion points with them? Thank you.

好的。偉大的。這是克萊爾為凱利代言的。感謝您提出我們的問題。所以想知道您是否可以就您與歐洲機構的初次會議提供更多資訊。您向他們展示了哪些數據？對於後續的會議，您能告訴我們與他們討論的重點是什麼嗎？謝謝。

Okay So we're not going to disclose much detail other than the following. And the reason we're not going to disclose much details is because we do not want background efforts to basically stop another agency from doing what they think is the right thing to do. And if you can read between the lines of what I'm saying, I think it will be very clear in the future to know that all these interactions are confidential.

好的，除了以下內容之外，我們不會透露太多細節。我們不打算透露太多細節的原因是我們不希望後台工作基本上阻止另一個機構做他們認為正確的事情。如果你能讀懂我所說的字裡行間，我想將來你會很清楚地知道所有這些互動都是保密的。

We've had the very initial interaction with one of the major agencies. And I will tell you their stance on this is diametrically opposite to the US FDA, diametrically opposite. What do I mean by that? They have done their homework. They understand the data, they have had slightly more mature data than what we had presented with to the FDA. Because, as you know, the FDA has very strict rules on not considering data post-submission of the package, and between the submission of the package and the meeting could be several months.

我們已經與主要機構之一進行了最初的互動。而且我告訴你他們在這方面的立場和美國FDA是截然相反的，截然相反的。我這麼說是什麼意思？他們已經做好功課了。他們了解這些數據，他們擁有的數據比我們向 FDA 提供的數據稍微成熟一些。因為，如您所知，FDA 有非常嚴格的規定，不考慮軟體包提交後的數據，並且從提交軟體包到會議之間可能需要幾個月的時間。

So even though we had more mature data by the time we had the actual meeting, this data wasn't being formally considered in their consideration of their guidance to us. But the European agency has seen this more mature data, and their guidance to us is very simple, that they have indicated several pointers that will be helpful to us in making sure that we meet all the requirements. But they've also said to us that they hope that these requirements, which are important box-checking elements, will not get in the way of our rapid exploration of submission.

因此，即使我們在召開實際會議時擁有了更成熟的數據，但在考慮對我們的指導時並沒有正式考慮這些數據。但歐洲機構已經看到了這些更成熟的數據，他們對我們的指導非常簡單，他們指出了一些指示，這將有助於我們確保我們滿足所有要求。但他們也對我們表示，他們希望這些要求是重要的檢查元素，不會妨礙我們快速探索提交。

Madison El-Saadi, B. Riley Financial.

Madison El-Saadi，B. Riley Financial。

Hey, guys, thanks for taking the question. Couple for me. Just as we look at this November dataset, kind of just wondering what the expectations on survival and durability are if we're looking for specifically just kind of maintain that 19.5%/20% ORR.

嘿，夥計們，謝謝你提出問題。對我來說是情侶。正如我們查看 11 月的資料集一樣，我們想知道如果我們專門尋找保持 19.5%/20% ORR 的目標，那麼對存活率和持久性的期望是什麼。

And then, could you also confirm, I'm sorry if I missed it, could you confirm that the two patients that had not had their confirmatory scan if they did have those scans? And then, lastly, on the Phase 3 design, just wondering thoughts on the control arm, if it'll look like the Phase 3, or if it could be different? Thanks.

然後，您能否確認一下，如果我錯過了，我很抱歉，您能否確認這兩名沒有進行確認掃描的患者是否進行了這些掃描？最後，關於第三階段的設計，只是想知道對控制臂的想法，它是否看起來像第三階段，或者是否可能有所不同？謝謝。

Okay. So number one, all of the data that we reported are strictly confirmed ORR, okay? Which means that there is still some upside to that, but there is no downside to it. In other words, we will not have any downside revision to what we have already reported as overall response rates in the second trial, the Phase 2 trial, multi-arm Phase 2 trial.

好的。所以第一，我們報告的所有數據都經過嚴格確認的 ORR，好嗎？這意味著這仍然有一些好處，但沒有壞處。換句話說，我們不會對第二次試驗、第二階段試驗、多臂第二階段試驗中已經報告的整體緩解率進行任何負面修正。

Now, of course, from the Phase 1 trial, we almost have 24 months of follow-up. And as we said earlier, the follow-up in the Phase 2 trial will be at a point of about 12-month maturity. And the trends that we're seeing in the Phase 2 trial are almost identical to the trends that we have seen in our Phase 1 trial.

當然，從第一階段試驗開始，我們幾乎有 24 個月的追蹤時間。正如我們之前所說，第二階段試驗的後續階段將在大約 12 個月的時間點成熟。我們在第二階段試驗中看到的趨勢與我們在第一階段試驗中看到的趨勢幾乎相同。

And so with all of that, we are confident about the integrity of our data. We're confident about the patient selection. In other words, there's no cheating here. All patients that are enrolled in this trial fall into the category of either third or fourth line patients in the metastatic study. So that has been confirmed. And of course, that adds to the validity of the data.

因此，我們對資料的完整性充滿信心。我們對患者的選擇充滿信心。換句話說，這裡沒有作弊。參加本試驗的所有患者均屬於轉移研究中的三線或四線患者類別。所以這已經被證實了。當然，這增加了數據的有效性。

And as Dr. O'Day would say, deep, underlining deep; and durable, underlining durable responses in immune oncology trials that are particularly mediated with a CTLA-4 binding antibody. As you know, BOT doesn't just bind to CTLA-4, it is a multifunctional antibody, but one of the things that it does is bind to CTLA-4.

正如奧戴博士所說，深刻，強調深刻；持久，強調免疫腫瘤學試驗中特別由 CTLA-4 結合抗體介導的持久反應。如您所知，BOT 不僅僅與 CTLA-4 結合，它是一種多功能抗體，但它的作用之一就是與 CTLA-4 結合。

We are confident that in an immuno-oncology treatment setting, any trial that is an IO-IO trial that binds to CTLA-4 and shows significant overall response rates always translates to survival benefit. I think this is a point that certain agencies understand, and other agencies like the FDA, I think, need to be schooled in this phenomenon.

我們相信，在免疫腫瘤治療環境中，任何與 CTLA-4 結合併顯示出顯著整體緩解率的 IO-IO 試驗始終會轉化為生存獲益。我認為某些機構理解這一點，我認為 FDA 等其他機構需要接受這種現象的教育。

And it is, frankly, our responsibility, not the FDA's responsibility, for us to present the data to convince them of the reality of the power of immuno-oncology with IO-IO agents that are mediated with CTLA-4 binding in addition to PD-1. Next question.

坦白說，我們有責任，而不是 FDA 的責任，讓我們提供數據，讓他們相信除了 PD 之外，透過 CTLA-4 結合介導的 IO-IO 藥物進行免疫腫瘤學的力量。下一個問題。

Madeline Stone, William Blair.

瑪德琳‧斯通，威廉‧布萊爾。

Great. Hi. This is Madeline on for Matt Phipps. Thanks for taking our question. So for future discussions planned with the FDA, how much additional follow-up from the Phase 2 trial will you need in that more mature dataset?

偉大的。你好。我是馬德琳，為馬特‧菲普斯代言。感謝您提出我們的問題。因此，對於計劃與 FDA 進行的未來討論，您需要在更成熟的資料集中對第二階段試驗進行多少額外的後續？

Approximately six more months of follow-up versus what we had presented to them in a submitted document.

與我們在提交的文件中向他們提供的內容相比，大約需要六個月的後續行動。

That concludes our question-and-answer session. I will now turn the conference back over to Garo Armen for closing remarks.

我們的問答環節到此結束。現在我將把會議轉回加羅·阿曼致閉幕詞。

Thank you very much, Leonardo. And, once again, thank you for your attention. I appreciate the questions that we've gotten. And the basic conclusion that I had is that I know we've made reference to the fact that we will be having more follow-up on patients before we engage with regulatory agencies, including the FDA.

非常感謝你，萊昂納多。再次感謝您的關注。我很感激我們收到的問題。我得出的基本結論是，我知道我們已經提到了這樣一個事實：在與包括 FDA 在內的監管機構合作之前，我們將對患者進行更多追蹤。

But I'd like to further indicate to you that we feel confident in the follow-up data from this trial because we have the data, by and large, and it will be only a question of cleaning up the data and presenting it in a format with the appropriate arguments that will hopefully align our way of thinking, our KOLs' way of thinking, our investigators who have significant experience in the field with our agents, their way of thinking with the regulatory.

但我想進一步向您表明，我們對本次試驗的後續數據充滿信心，因為總的來說，我們擁有數據，這只是清理數據並將其以一種形式呈現的問題。讓我們的思維方式、我們的KOL 的思維方式、我們在該領域擁有豐富經驗的調查人員與我們的代理人、他們的思維方式與監管機構保持一致。

So this is what we hope to accomplish in the next few months. And stay tuned, and we always welcome your engagement in the form of offline additional questions that you may have. Thank you again.

這就是我們希望在未來幾個月內實現的目標。請繼續關注，我們始終歡迎您以線下其他問題的形式參與。再次感謝您。

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝大家的加入。您現在可以斷開連線。