Agenus Inc (AGEN) 2023 Q4 法說會逐字稿

Good morning. My name is Audra, and I will be your conference operator today. At this time, I would like to welcome everyone to the Agenus Inc., fourth-quarter and full-year 2023 results conference call. Today's conference is being recorded. (Operator Instructions)

早安.我叫奧德拉，今天我將擔任你們的會議操作員。此時，我歡迎大家參加 Agenus Inc. 2023 年第四季和全年業績電話會議。今天的會議正在錄製中。（操作員說明）

At this time, I would like to turn the conference over to Zack Armen, Head of Investor Relations. Please go ahead.

這次，我想將會議交給投資者關係主管 Zack Armen。請繼續。

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

謝謝奧德拉，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、時間表的聲明，以及數據發布和合作機會的時間表以及其他更新。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; and Dr. Todd Yancey, Chief Strategic Advisor, 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。羅賓·泰勒博士，首席商務官；首席策略顧問 Todd Yancey 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 2023 and to speak to our outlook for 2024. Garo.

現在，我想將電話轉給 Garo，強調我們在 2023 年取得的進展，並談談我們對 2024 年的展望。加羅。

Thank you very much. Ladies and gentlemen, today, it is with great enthusiasm that we gather to share the remarkable strides Agenus has made over the past year. Our journey has been marked by significant achievements, pivotal milestones, and a steadfast commitment to innovation in the field of oncology. In 2023, Agenus reached crucial milestones, particularly with our BOT/BAL program, a cornerstone of our operational focus.

非常感謝。女士們、先生們，今天，我們懷著極大的熱情聚集在一起，分享 Agenus 在過去一年中所取得的顯著進步。我們的旅程以重大成就、關鍵里程碑以及對腫瘤學領域創新的堅定承諾為標誌。2023 年，Agenus 實現了重要的里程碑，特別是我們的 BOT/BAL 計劃，這是我們營運重點的基石。

BOT/BAL therapy has undergone rigorous testing in over 900 patients, demonstrating promising activity in cancers that represent significant unmet medical needs, notably colon cancer, where we are poised for potential first approval. The impressive response rates, sustained durability, and overall clinical efficacy observed across multiple challenging cancer types have garnered the attention and excitement from leading experts in the field.

BOT/BAL 療法已在 900 多名患者中進行了嚴格的測試，表明在代表重大未滿足醫療需求的癌症中具有良好的活性，特別是結腸癌，我們準備在該領域首次獲得批准。在多種具有挑戰性的癌症類型中觀察到的令人印象深刻的緩解率、持續的耐久性和整體臨床療效引起了該領域領先專家的關注和興奮。

It is essential to note that the patients enrolled in our trials have exhausted available standard treatments, making clinical responses achieved all the more meaningful. Our achievements in the past year underscore the immune potential -- immense potential of botensilimab, both as a standalone therapy and in combination with balstilimab and/or chemotherapy. All of these trials are currently ongoing.

值得注意的是，參加我們試驗的患者已經用盡了可用的標準治療方法，這使得所取得的臨床反應更有意義。我們在過去一年中所取得的成就強調了免疫潛力——博替利單抗的巨大潛力，無論是作為獨立療法還是與巴斯蒂利單抗和/或化療聯合使用。所有這些試驗目前正在進行中。

The presentation of our data at six prestigious scientific forums and publication in five peer-reviewed journals is a testament to the robustness and significance of our findings. Dr. O'Day will delve into the clinical data shortly, providing more detailed insights during this call.

我們的數據在六個著名的科學論壇上的展示以及在五個同行評審期刊上的發表證明了我們研究結果的穩健性和重要性。奧戴博士很快就會深入研究臨床數據，在這次電話會議中提供更詳細的見解。

The resounding feedback from over 1,000 physicians we engaged with over the past year underscores the transformative impact of our work and the impact it could have on patient care. Furthermore, the Fast Track Designation granted by the FDA acknowledges the urgent need for new treatments in our lead indications, which is refractory MSS CRC in non-liver metastatic patients.

去年與我們合作的 1,000 多名醫生的強烈回饋強調了我們工作的變革性影響及其對患者護理可能產生的影響。此外，FDA 授予的快速通道資格承認我們的主要適應症迫切需要新的治療方法，即非肝轉移患者的難治性 MSS CRC。

As we stand on the threshold of a clinical and a critical phase in our regulatory journey, our focus is squarely on advancing activities for a potential accelerated approval filing. Our immediate efforts are directed towards ensuring that our development strategies align seamlessly with the FDA's rigorous standards.

當我們正處於臨床階段和監管旅程的關鍵階段時，我們的重點是推動潛在的加速審批申請活動。我們目前的努力旨在確保我們的開發策略與 FDA 的嚴格標準無縫銜接。

In 2024, our primary objective is to pursue a global regulatory strategy for BOT/BAL in our Fast Track indication. Following the alignment with the FDA, we intend to initiate the submission of our biologics license application, otherwise known as a BLA, for potential accelerated approval.

2024 年，我們的主要目標是在我們的快速通道適應症中推行 BOT/BAL 的全球監管策略。在與 FDA 達成協議後，我們打算開始提交我們的生物製品許可申請（也稱為 BLA），以加快批准速度。

Subsequently, pending feedback from scientific and regulatory advice in Europe, we plan to submit to the European Medicines Agency, known as the EMA, in 2025. To achieve our regulatory objectives, we are intensifying our efforts to provide regulatory authorities with a comprehensive data package that demonstrates the safety, efficacy, and clinical pharmacology of BOT/BAL in refractory MSS CRC.

隨後，在等待歐洲科學和監管建議的回饋後，我們計劃於 2025 年向歐洲藥品管理局（即 EMA）提交。為了實現我們的監管目標，我們正在加緊努力，為監管機構提供全面的資料包，證明 BOT/BAL 在難治性 MSS CRC 中的安全性、有效性和臨床藥理學。

Our Phase 2 study completed in October 2023 -- or I should say completed enrollment in 2023 was meticulously designed to evaluate BOT/BAL's dosage and the contribution of its components. Additionally, by the end of 2024, we anticipate initiating a Phase 3 study in the patient population of our proposed indication.

我們的 2 期研究於 2023 年 10 月完成，或者我應該說 2023 年完成的入組是經過精心設計的，旨在評估 BOT/BAL 的劑量及其成分的貢獻。此外，到 2024 年底，我們預計將針對我們提議的適應症的患者群體啟動一項 3 期研究。

Our commitment to transparency and stakeholder engagement remains unwavering as we progress towards delivering these potentially life-altering treatments to patients. Looking ahead, our mission to enhance the lives of cancer patients to the power of the immune system remains steadfast.

隨著我們向患者提供這些可能改變生活的治療方法的進展，我們對透明度和利害關係人參與的承諾仍然堅定不移。展望未來，我們的使命仍然堅定不移，即利用免疫系統的力量來改善癌症患者的生活。

That's been our mission from day one, 30 years ago, of course, today, with BOT/BAL leading the charge in our dynamic portfolio of agents. To expedite this transformative journey, we are actively exploring strategic partnerships. Our ongoing collaborations have already yielded significant returns, exemplified, for example, by the recent $25 million milestone payment from BMS, triggered by the commencement of a Phase 2 study with BMS-986442. This is a TIGIT bispecific antibody discovered and the early development was done by Agenus, and it was licensed to BMS.

從 30 年前的第一天起，這就是我們的使命，當然，今天，BOT/BAL 在我們充滿活力的代理商組合中處於領先地位。為了加快這趟變革之旅，我們正在積極探索策略夥伴關係。我們正在進行的合作已經產生了顯著的回報，例如，最近 BMS 因 BMS-986442 2 期研究的啟動而支付了 2500 萬美元的里程碑付款。這是一種TIGIT雙特異性抗體，早期由Agenus開發，並授權給BMS。

We have received a total of $250 million from this collaboration thus far. Moreover, we are progressing our efforts to monetize non-core assets and explore royalty financing and project funding opportunities with the potential to generate an additional $100 million to $200 million in the relatively near term. Furthermore, we're engaged in discussions with several prospective pharmaceutical partners, exploring avenues for co-marketing and co-development agreements, specifically for BOT/BAL.

迄今為止，我們已從此次合作中獲得了總計 2.5 億美元的資金。此外，我們正在努力將非核心資產貨幣化，並探索特許權使用費融資和專案融資機會，有可能在短期內額外產生 1 億至 2 億美元的資金。此外，我們正在與幾個潛在的製藥合作夥伴進行討論，探索聯合行銷和聯合開發協議的途徑，特別是 BOT/BAL。

Dr. O'Day will now provide an overview of our latest clinical findings, further illuminating the groundbreaking progress we've made so far. Thank you for your continued support and confidence in Agenus. Together, we are pioneering a new era in cancer treatment, one that offers hope and healing to patients worldwide. Dr. O'Day.

O'Day 博士現在將概述我們最新的臨床發現，進一步闡明我們迄今為止的突破性進展。感謝您對 Agenus 一如既往的支持和信任。我們共同開創了癌症治療的新時代，為全世界的患者帶來希望和治癒。奧戴博士。

Thank you, Garo. Together with our investigators and key opinion leaders, we presented updates from BOT/BAL development program at ASCO GI to Society of Gynecologic Oncology, ESMO GI, CTOS, and at a corporate event hosted during the ESMO Congress in October. Throughout 2023, new clinical data was presented for nearly all of our programs, and I refer you to our press release issued today that provides a comprehensive summary of our 2023 clinical development updates.

謝謝你，加羅。我們與我們的研究人員和關鍵意見領袖一起，向婦科腫瘤學會、ESMO GI、CTOS 以及 10 月份 ESMO 大會期間舉辦的企業活動介紹了 ASCO GI 的 BOT/BAL 開發計劃的最新情況。在整個 2023 年，我們幾乎所有項目都發布了新的臨床數據，我建議您參閱我們今天發布的新聞稿，其中全面總結了我們 2023 年臨床開發更新。

Today, I'd like to share a selection of our data updates from the last year, which highlights some of the compelling opportunities we have to transform care for patients.

今天，我想分享我們去年的一些數據更新，其中強調了我們在改變患者護理方面所面臨的一些引人注目的機會。

Starting with safety, we continue to observe a manageable safety profile. As of May 2023 data cut from our solid tumor Phase 1b study, with doses of 1 milligram per kilo or 2 milligrams per kilo of botensilimab in combination with balstilimab, the most common adverse events were immune related, and the most common of these were diarrhea and colitis. Grade 3 or greater treatment-related diarrhea/colitis occurred in 14% of patients.

從安全開始，我們繼續觀察可控的安全狀況。截至2023 年5 月，我們實體瘤1b 期研究的數據截取，使用劑量為每公斤1 毫克或每公斤2 毫克的博替利單抗與巴斯蒂利單抗合併用藥時，最常見的不良事件與免疫相關，其中最常見的是腹瀉和結腸炎。14% 的患者出現 3 級或以上的治療相關性腹瀉/結腸炎。

These findings are consistent with the mechanism of action of bot and bal as both are immuno-oncology agents. Now, turning to our CRC development program for bat and bal, where we have made significant progress. As of our latest update during our corporate event in October 2023, our Phase 1b expanded cohort of 70 evaluable patients had a median follow-up now of 12.3 months, and RECIST confirmed the overall response rate of 24%. Based on literature review, the response rate in a similar population treated with standard of care therapies ranges from 1% to 6%.

這些發現與 bot 和 bal 的作用機制一致，因為兩者都是免疫腫瘤藥物。現在，轉向我們針對 bat 和 bal 的 CRC 開發計劃，我們已在該計劃中取得了重大進展。截至 2023 年 10 月公司活動期間的最新更新，我們的 1b 期擴展隊列由 70 名可評估患者組成，中位追蹤時間為 12.3 個月，RECIST 確認總體緩解率為 24%。根據文獻綜述，接受標準護理療法治療的類似族群的緩解率在 1% 至 6% 之間。

In addition, patients in our trial showed a 12-month overall survival rate of 74%. Median overall survival has not been reached. We anticipate having top-line data from the Phase 2 trial publicly available in the second half of 2024 to align with our planned regulatory timeline and allow for sufficient data maturation.

此外，我們試驗中的患者 12 個月的總體存活率為 74%。尚未達到中位總存活期。我們預計 2024 年下半年將公開第二階段試驗的主要數據，以符合我們計畫的監管時間表，並讓數據充分成熟。

At ASCO GI in January of this year, data was presented from an investigator-sponsored trial being conducted by Dr. Pashtoon Kasi at Weill-Cornell Medical Center, in which 12 patients with colorectal cancer were treated with one dose of bot at 75 milligrams and two doses of balstilimab at 240 milligrams in a neoadjuvant therapy window of opportunity setting.

在今年1 月的ASCO GI 上，公佈了由Pashtoon Kasi 博士在威爾康奈爾醫學中心進行的一項由研究者資助的試驗的數據，其中12 名結直腸癌患者接受了75 毫克的一劑bot 治療，在新輔助治療機會窗口中接受兩劑 240 毫克的巴司替利單抗。

Surgery was performed, on average, four weeks after the initiation of immunotherapy. All three of three MSI high colorectal patients had complete or near complete pathologic responses. And even more importantly, six out of nine patients with MS-stable colorectal cancer had pathologic responses of 50% or greater in two -- including two complete pathologic responses.

手術平均在免疫治療開始後四週進行。三名 MSI 高結腸直腸患者中的三名均具有完全或接近完全的病理反應。更重要的是，在九名MS 穩定大腸直腸癌患者中，有六名患者的病理緩解率達到50% 或更高，其中兩名患者的病理緩解率達到或更高，其中兩名患者的病理緩解率為完全。

None of the 12 patients had tumor growth during the treatment interval, and no surgeries were delayed during -- delayed due to immune-related toxicities. There were only two instances of Grade 3 treatment-related adverse events, diarrhea and fatigue, which were reversible. These results represent an important opportunity to move into earlier non-metastatic lines of therapy and potentially change the treatment paradigm, particularly for early-stage MS-stable colorectal cancer. This IST is currently adding an additional 24 patients.

12 名患者在治療期間均未出現腫瘤生長，也沒有因免疫相關毒性而延遲手術。只有兩例 3 級治療相關不良事件：腹瀉和疲勞，這些不良事件是可逆的。這些結果代表了進入早期非轉移性治療線的重要機會，並有可能改變治療模式，特別是對於早期 MS 穩定的大腸直腸癌。該 IST 目前正在新增 24 名患者。

The expansion extends dosing of immunotherapy and the timing of surgery from four to six to eight weeks, which is more reflective of traditional neoadjuvant therapy studies. Depending on the data, we plan to prioritize neoadjuvant development and are evaluating study designs for further pivotal studies. And lastly, in second-line pancreatic cancer, we reported data on six patients with the combination of botensilimab with two chemotherapy agents, gemcitabine and ABRAXANE, as a triplet therapy. All six patients had progressed following the most aggressive first-line metastatic regimen of FOLFIRINOX chemotherapy, and all six had liver metastases.

此次擴展將免疫治療的劑量和手術時間從四週延長至六週至八週，更能反映傳統的新輔助治療研究。根據數據，我們計劃優先考慮新輔助開發，並正在評估研究設計以進行進一步的關鍵研究。最後，在二線胰臟癌中，我們報告了 6 名患者接受博替尼單抗與兩種化療藥物吉西他濱和 ABRAXANE 聯合作為三重療法的數據。所有六名患者在接受最積極的一線轉移方案 FOLFIRINOX 化療後均出現進展，並且所有六名患者均出現肝轉移。

Four of the patients achieved marked and sustained tumor marker reductions. We reported two of the four patients achieving a partial response at 16 weeks, with a confirmed target lesion reductions of 47% and 37%, which was pending confirmation at the time the data was reported. Two other patients showed stable disease at their first eight-week scan, with tumor reductions of 20% and 13%, respectively. A randomized phase 2 study is currently enrolling, and we anticipate preliminary data being available in the second half of this year.

其中四名患者的腫瘤標記顯著且持續降低。我們報告稱，四名患者中的兩名在 16 週時實現了部分緩解，已確認目標病變減少了 47% 和 37%，但在報告數據時尚待確認。另外兩名患者在首次八週掃描時顯示疾病穩定，腫瘤分別縮小了 20% 和 13%。一項隨機 2 期研究目前正在招募中，我們預計今年下半年將提供初步數據。

These results demonstrate clear activity of botensilimab in cold tumors in both the refractory setting and in early disease, combining botensilimab with either balstilimab or chemotherapy. And this offers hope for patients and families where current standards provide limited benefit. We remain committed to improving patient outcomes and are grateful for the support of our team, trial participants, and stakeholders.

這些結果表明，將博替利單抗與巴司替利單抗或化療相結合，博替利單抗在難治性冷腫瘤和早期疾病中均具有明顯的活性。這為當前標準提供的益處有限的患者和家庭帶來了希望。我們仍然致力於改善患者的治療效果，並感謝我們的團隊、試驗參與者和利害關係人的支持。

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

現在，我將把電話轉給克里斯汀討論財務問題。

Thank you, Steven. For the year ended December 31, 2023, we recognized revenue of $156 million and incurred a net loss of $257 million or $0.69 per share. For the fourth quarter ended December 31, 2023, we recognized revenue of $84 million and incurred a net loss of $49 million or $0.13 per share. Revenue primarily includes revenue under our collaboration agreements, including milestones achieved, and revenue related to non-cash royalties earned.

謝謝你，史蒂文。截至 2023 年 12 月 31 日的年度，我們確認營收為 1.56 億美元，但淨虧損為 2.57 億美元，即每股虧損 0.69 美元。截至 2023 年 12 月 31 日的第四季度，我們確認營收為 8,400 萬美元，但淨虧損 4,900 萬美元，即每股虧損 0.13 美元。收入主要包括我們的合作協議下的收入，包括實現的里程碑以及與所賺取的非現金特許權使用費相關的收入。

We ended the year with $76 million in cash. Subsequent to which, in January 2024, we received the $25 million milestone payment from BMS, triggered by the commencement of a Phase 2 study with BMS-986442, the Agenus-discovered TIGIT bispecific antibody. Additionally, we've progressed in monetizing nonstrategic assets and future milestones and royalties from ongoing partnerships. These efforts are expected to yield significant cash proceeds by mid-2024.

年底我們擁有 7,600 萬美元現金。隨後，在 2024 年 1 月，我們收到了 BMS 的 2500 萬美元里程碑付款，這是由 Agenus 發現的 TIGIT 雙特異性抗體 BMS-986442 的 2 期研究開始引發的。此外，我們在非策略性資產貨幣化、未來里程碑以及來自持續合作夥伴關係的特許權使用費方面取得了進展。這些努力預計將在 2024 年中期產生大量現金收益。

Accordingly, we anticipate being funded through 2024. In parallel, we're pursuing potential partnership discussions with five biopharmaceutical parties to further expand our cash resources.

因此，我們預計到 2024 年都能獲得資助。同時，我們正在與五個生物製藥方進行潛在的合作討論，以進一步擴大我們的現金資源。

I'll now turn the call back to Garo.

我現在將電話轉回加羅。

Thank you, Steven and Christine. As we look ahead, of course, we're excited about the opportunities that await both cancer patients and Agenus in 2024. Our steadfast dedication remains centered on providing cancer patients with enhanced treatment options, a mission that not only benefits patients but also enhances the shareholder value and secures the long-term prosperity of our company through continued innovation. Innovation has been critical to our existence and our growth, and it will continue to be.

謝謝你們，史蒂文和克里斯汀。當然，展望未來，我們對 2024 年等待癌症患者和 Agenus 的機會感到興奮。我們堅定不移的奉獻精神仍然集中在為癌症患者提供更好的治療選擇，這項使命不僅使患者受益，而且還提高股東價值，並透過持續創新確保我們公司的長期繁榮。創新對於我們的生存和發展至關重要，也將繼續如此。

This year, a paramount objective for us is to present a compelling data package to the FDA, seeking their consent to initiate the filing of our biologics license application. At Agenus, pioneering advancements in oncology has been more than a mission for us. It's been our enduring commitment for many years. We extend our heartfelt gratitude to our shareholders, partners, and the entire Agenus team for their unwavering support.

今年，我們的首要目標是向 FDA 提交令人信服的資料包，尋求他們的同意啟動我們的生物製品許可申請。在 Agenus，腫瘤學領域的開創性進步不僅僅是我們的使命。這是我們多年來持久的承諾。我們衷心感謝我們的股東、合作夥伴以及整個 Agenus 團隊的堅定支持。

Together, we stand at the threshold of a transformative journey, one poised to make a profound impact on the lives of patients worldwide, with the ultimate aim of delivering chemotherapy-free treatment options.

我們共同站在變革之旅的起點，這趟旅程將對全世界患者的生活產生深遠影響，最終目標是提供免化療的治療選擇。

Thank you very much for your time and attention. And now, we invite any questions that you may have. Audra?

非常感謝您的時間和關注。現在，我們歡迎您提出任何問題。奧德拉？

(Operator Instructions)

（操作員說明）

Emily Bodnar, H.C. Wainwright.

艾米莉·博德納爾，H.C.溫賴特。

Hi. Good morning and thanks for taking the question. My first is on the neoadjuvant CRC study. You mentioned that you're extending the treatment period from four weeks to six to eight weeks. So curious if you could discuss how you think the longer treatment period may impact efficacy and if there are certain metrics that you think could improve with the greater treatment period, and also if you're following patients in that study post-surgery to eventually look at their surgical outcomes.

你好。早上好，感謝您提出問題。我的第一個研究是新輔助大腸直腸癌研究。您提到您將治療時間從四週延長到六到八週。很好奇您是否可以討論您認為較長的治療期可能如何影響療效，以及您認為是否有某些指標可以隨著較長的治療期而改善，以及您是否在手術後跟踪該研究中的患者以最終觀察他們的手術結果。

And then second question on MSS CRC. Could you just confirm the timing of the BLA submission? I believe you were previously saying mid-2024. So, is that still on track, or is that looking more like second half now? Thank you.

然後是關於 MSS CRC 的第二個問題。您能否確認一下 BLA 提交的時間？我相信您之前說的是 2024 年中期。那麼，這是否仍然在正軌上，或者現在看起來更像是下半場？謝謝。

So Emily, I'll start with the last question, on the timing of the BLA submission. So as we've guided investors before, the very first step for us is to meet with the FDA, which we're planning on doing mid-year, and they're giving their specific guidance on our BLA submission. So we do not want to jump the gun ahead of that meeting and provide different guidance than what we will get out of that FDA meeting.

Emily，我將從最後一個問題開始，即 BLA 提交的時間。因此，正如我們之前指導投資者的那樣，我們的第一步是與 FDA 會面，我們計劃在年中進行，他們正在就我們的 BLA 提交提供具體指導。因此，我們不想在這次會議之前操之過急，提供與 FDA 會議中不同的指導。

So bear with us. I think we're talking about only a few months from now that we will be able to give you a much more specific guidance on our BLA submission.

所以請耐心等待。我認為我們談論的只是幾個月後，我們能夠為您提供有關 BLA 提交的更具體的指導。

Garo, would you like me to --

加羅，你願意我嗎--

Yes.

是的。

Emily, in terms of the --

艾米麗，就--

Neoadjuvant -- the very exciting neoadjuvant data, very exciting. And in fact, when I was talking to one of our long-term advisors yesterday, the first thing he mentioned in the conversation was how remarkable this neoadjuvant data has been because of all the reasons you cited, Emily, and Dr. O'Day will elucidate further.

新輔助－非常令人興奮的新輔助數據，非常令人興奮。事實上，當我昨天與我們的長期顧問交談時，他在談話中提到的第一件事是，由於艾米麗和奧戴博士您引用的所有原因，這種新輔助數據是多麼引人注目將進一步闡明。

Thank you, Garo. Emily, yes, I mean, given that MS-stable colorectal cancer immune therapy has not previously been effective, the four-week window period was what surgeons were comfortable with allowing, which was essentially no delay in the surgery. And these results are remarkable in terms of the percentage of patients with deep tumor regressions in four weeks.

謝謝你，加羅。艾米麗，是的，我的意思是，考慮到 MS 穩定的結直腸癌免疫療法以前並不有效，所以外科醫生可以接受四個星期的窗口期，這基本上不會延遲手術。就四週內腫瘤深度消退的患者百分比而言，這些結果是顯著的。

So the extension of the study will allow now a proper six- to eight-week treatment period. And we do anticipate that over that time, we will see further deepening of responses. So we're looking forward to that. The study is looking at surgical outcomes and obviously post-surgery relapses. So this will be a comprehensive neoadjuvant study.

因此，研究的擴展現在將允許適當的六到八週的治療期。我們確實預計，在那段時間裡，我們將看到反應的進一步深化。所以我們對此充滿期待。該研究正在研究手術結果和明顯的手術後復發。所以這將是一項全面的新輔助研究。

Okay. Great. Thanks so much.

好的。偉大的。非常感謝。

Mayank Mamtani, B. Riley Securities

Mayank Mamtani，B. Riley 證券

Good morning. Thanks for taking our questions and appreciate the comprehensive update. So maybe just on the Phase 2 MSS CRC data, are you able to comment on what statistically we should be focused on and if the slight push out here is relating to you wanting to have OS data or mature durability data, which I could see makes sense if you're thinking about Phase 3 design?

早安.感謝您提出我們的問題並感謝全面的更新。因此，也許就第 2 階段 MSS CRC 數據而言，您能否評論一下我們應該關注哪些統計數據？這裡的輕微推出是否與您想要擁有操作系統數據或成熟的耐用性數據有關，我認為這使得您是否正在考慮第三階段的設計？

And maybe if you could also comment on thinking and timing for launching that Phase 3. Should we be aware of any planned regulatory meetings, discussions around that? Then I have a couple of follow-ups.

也許您也可以評論一下啟動第三階段的想法和時機。我們是否應該了解任何計劃中的監管會議以及相關討論？然後我有一些後續行動。

Yeah. So as you know, we have -- as we said before, we've completed enrollment in October. And typically, 80% of the patients respond within six months of the first dose. So, when we complete enrollment, by the time the patients get the first dose, you're talking about November.

是的。如您所知，正如我們之前所說，我們已於 10 月完成註冊。通常，80% 的患者在第一次給藥後六個月內出現反應。因此，當我們完成登記時，當患者接受第一劑疫苗時，您談論的是 11 月。

And by the time we get the six-month readout or 80% of the responses, it's sometime around May. Now, needless to say, we have already started cleaning up the data and all of the nitty-gritty process so that we can provide all of the outcomes as soon as possible. So it will be in the next few months. And our first step is to share this data with the FDA because the timing of the data generation and the FDA meeting will be very close. And then after the FDA meeting, we plan on making top-line data public appropriately.

當我們得到 6 個月的數據或 80% 的回應時，已經是 5 月左右的某個時間了。現在，不用說，我們已經開始清理資料和所有具體流程，以便我們能夠盡快提供所有結果。未來幾個月也是如此。我們的第一步是與 FDA 分享這些數據，因為數據產生的時間和 FDA 會議的時間將非常接近。然後在 FDA 會議之後，我們計劃適當地公開主要數據。

Phase 3 design, timing of launch, if you could comment on that for MSS CRC?

第三階段設計、啟動時間，您能否對 MSS CRC 對此發表評論？

Steven, would you like to take that, please?

史蒂文，你願意接受這個嗎？

Yes. I mean, our plans with the Phase 3 trial is in the same line of therapy as the Phase 2, and we anticipate getting that trial started by the end of the year so it can be substantially enrolled at a potential PDUFA date in 2025.

是的。我的意思是，我們的 3 期試驗計劃與 2 期試驗採用相同的治療方案，我們預計在今年年底開始該試驗，以便可以在 2025 年潛在的 PDUFA 日期大量入組。

Got it. And then you're being a bit more precise about your biopharma strategic discussions than you've been before. Garo, could you comment on what areas of more or less alignment that could unlock the [Coco] deal structure that it looks like you're prioritizing? And maybe how much does the neoadjuvant CRC opportunity kind of play a role because it obviously expands the market, but it also comes with a commitment of doing a long-term study?

知道了。然後你對生物製藥策略的討論比以前更精確了。Garo，您能否評論一下哪些領域或多或少的一致性可以解鎖您優先考慮的[Coco]交易結構？也許新輔助大腸癌機會能發揮多大作用，因為它顯然擴大了市場，但它也伴隨著進行長期研究的承諾？

I think it's very important to address your question in a way that doesn't violate any confidentiality. So we have, as you know, talked about partnering BOT/BAL for the last couple of years. Now of course, when we started our discussions with prospective partners, we had a fraction of the data we have today, fraction of the data. And thanks to our enthusiastic physicians, investigators, and of course, patient inquiries, we have had an explosive growth in our clinical trial enrollment.

我認為以不違反任何保密性的方式回答您的問題非常重要。如您所知，過去幾年我們一直在討論與 BOT/BAL 合作。當然，現在，當我們開始與潛在合作夥伴進行討論時，我們擁有今天擁有的數據的一小部分，一小部分數據。感謝我們熱情的醫生、研究人員，當然還有患者的詢問，我們的臨床試驗註冊人數出現了爆炸性增長。

I mean, if you look at, for example, our Phase 2 trial enrollment, we enrolled 230 patients in less than five months, which is a record that has surprised many people. Now with all of that, you would expect, of course, that there is a fair amount of enthusiasm by prospective pharmaceutical companies amid, as we've talked about earlier, all of the fascination with treatments that result in weight reduction and radio biopharmaceuticals, as well as ADCs. But when I ask a question to experts, I say do ADCs and biopharmaceuticals cure cancer? The answer is often not -- no.

我的意思是，例如，如果你看一下我們的 2 期試驗入組情況，我們在不到 5 個月的時間裡就入組了 230 名患者，這是一個讓很多人感到驚訝的記錄。有了這一切，你當然可以預料到，正如我們之前討論的那樣，未來的製藥公司對減肥和放射性生物製藥的治療方法充滿了熱情，以及 ADC。但當我向專家提問時，我說ADC和生物製藥可以治癒癌症嗎？答案往往是否定的——不。

Now, of course, we don't know if we're curing cancer. We don't know that. And the term, curing cancer, is a very dicey term because how do you demonstrate it? How do you clinically demonstrate curing cancer? And the only thing that we know for sure is that there's a product called Yervoy that has cured -- de facto cured a slice of melanoma patients, but it's been mostly restricted to melanoma. In fact, Dr. O'Day was one of the pioneers in clinical development of Yervoy.

當然，現在我們不知道我們是否能治癒癌症。我們不知道這一點。治癒癌症這個術語是一個非常危險的術語，因為你如何證明它？您如何在臨床上證明治癒癌症？我們唯一確定的是，有一種名為 Yervoy 的產品已經治癒了——事實上治癒了一部分黑色素瘤患者，但它主要局限於黑色素瘤。事實上，O'Day 博士是 Yervoy 臨床開發的先驅之一。

Now of course, one of the attributes of Yervoy is that it binds to CTLA-4, a very important receptor in the activation of the immune system, specifically T cells. Now we also know that our botensilimab binds to CTLA-4, but it does so many other things. So we are hopeful that, eventually, botensilimab's activity will be broader than what Yervoy's activity has been in melanoma.

當然，Yervoy 的特性之一是它與 CTLA-4 結合，CTLA-4 是活化免疫系統（特別是 T 細胞）中非常重要的受體。現在我們也知道我們的 botensilimab 與 CTLA-4 結合，但它還有很多其他作用。因此，我們希望最終，botensilimab 的活性將比 Yervoy 在黑色素瘤中的活性更廣泛。

And so with that, of course, we're excited about what we're going to be doing with it. And that begs the question of a like-minded partner that will put in the resources to develop botensilimab and balstilimab for the kinds of cancer patients that deserve it.

因此，當然，我們對我們將用它做的事情感到興奮。這就引出了一個志同道合的合作夥伴的問題，該合作夥伴將投入資源為那些值得的癌症患者開發博替利單抗和巴斯蒂利單抗。

Deserve it, meaning that our aim is that once we get the regulatory buy-in and we go for our first BLA filing, our aim is an explosive expansion for the development of botensilimab. Explosive expansion because, as you know, we've said, across nine different indications with varying denominators of 900 patients in total, we've seen some remarkable activity. There's no two ways about it. Remarkable activity.

當之無愧，這意味著我們的目標是，一旦獲得監管機構的支持並進行第一份 BLA 備案，我們的目標就是爆炸性擴展博滕西利單抗的發展。爆炸式擴張是因為，如您所知，我們已經說過，在總共 900 名患者的 9 種不同的適應症和不同的分母中，我們看到了一些顯著的活動。沒有兩種辦法。非凡的活動。

And that is, of course, the basis for why the right partner that will be selected, hopefully in the next several months, would be the partner, not just for us, but for the benefit of the patients to develop this product in the way it deserves to be developed.

當然，這就是為什麼選擇合適的合作夥伴（希望在接下來的幾個月內）將成為合作夥伴的基礎，不僅是為了我們，而且為了患者的利益，以這種方式開發該產品它值得開發。

So again, we have -- I think Christine slipped a number of active discussions. We have a number of active discussions right now that are going on. And unfortunately, on one hand, these discussions take a long time. Our longest corporate discussion that has resulted in a significant partnership has taken nearly two years. The shortest one was a year. So I'm not suggesting that the partnership is going to be a year from now, but I just want to give you guidance that these things take time.

所以，我們再次——我認為克里斯汀錯過了一些積極的討論。我們現在正在進行許多積極的討論。不幸的是，一方面，這些討論需要很長時間。我們歷時最長的企業討論花了近兩年的時間才形成了重要的合作關係。最短的是一年。因此，我並不是說合作關係將持續一年，但我只是想告訴您，這些事情需要時間。

Yes. Very helpful, Garo. And just maybe lastly on that remarkable activity, just on the pancreatic and this TKI-refractory lung cohort data, which seems new, could you talk to what patient numbers you're expecting to have in your mid- or second-half update for pancreatic and maybe lung, if you could comment on that? Thanks again for taking our question.

是的。非常有幫助，加羅。也許最後關於那個非凡的活動，關於胰腺和這個 TKI 難治性肺隊列數據，這似乎是新的，您能否談談您預計在中期或下半年更新胰腺的患者人數也許還有肺，您能對此發表評論嗎？再次感謝您提出我們的問題。

If I may ask either Steven or Todd to address this question. And if you have more specific clarification for the questions, please feel free to ask.

我可以請史蒂文或託德回答這個問題嗎？如果您對問題有更具體的說明，請隨時提問。

So yes, Mayank, in terms of pancreas, we have a randomized [Phase 3] trial, and we expect to treat 60 patients total, 30 on each arm. And that trial is actively accruing for further proof of concept. In terms of the lung data, we have expanded the cohort, as we've said, to approximately 50 patients. This data is maturing.

所以，是的，Mayank，就胰臟而言，我們有一項隨機 [第 3 階段] 試驗，我們預計總共治療 60 名患者，每組 30 名。該試驗正在積極進行，以進一步驗證概念。就肺部數據而言，正如我們所說，我們已將隊列擴大到大約 50 名患者。這個數據正在日趨成熟。

We're showing you the preliminary TKI data in our press release today. You can see in that very refractory TKI population of seven patients, we had two patients have responses, and both of them were complete. That -- the overall data continues to mature, and we'll have more data in the second half of the year to report.

我們在今天的新聞稿中向您展示了 TKI 的初步數據。您可以看到，在 7 名患者的非常難治性 TKI 人群中，我們有兩名患者有反應，而且兩人都是完全的。整體數據持續成熟，我們將在今年下半年有更多數據進行報告。

Great. Thanks for taking our questions.

偉大的。感謝您回答我們的問題。

Thank you, Mayank.

謝謝你，瑪雅克。

Colleen Kusy, Baird.

科琳·庫西，貝爾德。

Hi. Good morning. Thanks for taking our questions. Can you just comment, what are some of the outstanding items you think you need FDA feedback prior to the MSS CRC filing?

你好。早安.感謝您回答我們的問題。您能否評論一下，您認為在 MSS CRC 備案之前需要 FDA 回饋的一些突出項目有哪些？

Is the question what are the alignments with the FDA that will prompt the potential BLA filing?

問題是與 FDA 的哪些一致性將促使潛在的 BLA 備案？

Yes.

是的。

Okay. So we found -- first of all, we've made a strategic decision because we were moving -- as I said earlier, we were enrolling our clinical trials rapidly. For example, our Phase 2 trial enrolled very rapidly. And it was a very important trial for us to go to the agency was because of the dose selection, as well as the contribution of the elements.

好的。所以我們發現——首先，我們做出了策略決策，因為我們正在行動——正如我之前所說，我們正在迅速進行臨床試驗。例如，我們的二期試驗入組速度非常快。我們去該機構進行了一次非常重要的試驗，因為劑量的選擇，以及元素的貢獻。

And of course, we had also a small reference arm. Now of course, mind you, this trial is not powered statistically to show any differentiation between the arms. However, it is designed to address the Project Optimus questions. And so the question was for us, if we go to the agency and ask them a question in an abstract form, what is this, what is that, the answer is likely to be, well, when you have the data, come back to us, present it to us, and we'll give you an intelligent answer.

當然，我們還有一個小型參考臂。當然，請注意，該試驗沒有統計數據來顯示各組之間的任何差異。然而，它是為了解決擎天計畫問題而設計的。所以這個問題是對我們來說的，如果我們去機構並以抽象的形式問他們一個問題，這是什麼，那是什麼，答案很可能是，好吧，當你有數據時，回到請將其呈現給我們，我們將為您提供明智的答案。

And so in order to -- for us to be able to get to that point, we made a strategic decision, Colleen, that we would wait until all the data matured to the point where we had a compelling package with -- to present to the FDA. So that's the reason why we are waiting until the data matures, which will be, again, somewhat before the middle of this year.

因此，為了讓我們能夠達到這一點，我們做出了一個戰略決策，科琳，我們將等到所有數據都成熟到我們有一個令人信服的包時才能呈現給FDA。這就是我們等待數據成熟的原因，這將在今年年中之前進行。

And as you know, procedurally, requesting meetings and being granted meetings, sort of a discussion with a comprehensive data package takes a little time. So we are planning on asking for the meeting very soon and planning on having the meeting sometime around mid-year, plus or minus a month.

如您所知，從程序上來說，請求會議和獲準會議、使用全面資料包進行討論需要一些時間。因此，我們計劃很快要求召開會議，並計劃在年中左右的某個時間（前後一個月）舉行會議。

Great. Thanks. And then just one follow-up on the pancreatic development program. I know we'll have data from the Phase 2 trial mid-year. What would the next steps look like in the development path toward approval there?

偉大的。謝謝。然後是胰臟發育計劃的一項後續行動。我知道我們將在年中獲得第二階段試驗的數據。在獲得批准的發展道路上，下一步會是什麼樣子？

For the pancreatic?

對於胰臟？

Yes.

是的。

OK. So just to recap, the data package that we will go to the FDA with for the CRC indication is approximately 150 patients in our Phase 1 trial and 230 patients in our Phase 2 trial. Now with pancreatic, the next step for us, and I will ask Dr. Steven O'Day to elucidate more, but the next step for us is to look at the randomized data results from the expansion cohort of the existing trial.

好的。回顧一下，我們將向 FDA 提交的 CRC 適應症資料包包括約 150 名 1 期試驗患者和 230 名 2 期試驗患者。現在，對於胰腺，我們的下一步是，我將請 Steven O'Day 博士闡明更多信息，但我們的下一步是查看現有試驗擴展隊列的隨機數據結果。

As you know, we observed some remarkable activity in second-line pancreatic cancer patients that were treated with FOLFIRI and then relapsed. And the standard of care for them is gem-ABRAXANE. Now the standard of care, unfortunately, is not curative, and these patients relapsed within a short period of time. And in furthermore, the response rates for these patients, according to the experts and published information, is in the range of 10% to 15%. So we're talking about reference arm being 10% to 15% with response rates being very short in duration.

如您所知，我們在接受 FOLFIRI 治療但隨後復發的二線胰臟癌患者中觀察到了一些顯著的活性。他們的護理標準是 gem-ABRAXANE。不幸的是，現在的護理標準並不能治愈，而且這些患者在短時間內復發。此外，根據專家和已公佈的信息，這些患者的緩解率在 10% 至 15% 之間。因此，我們討論的參考組為 10% 到 15%，回應率持續時間非常短。

Now, of course, the denominator of the data that we presented is small, but the fact that all patients have seen a significant drop in their cancer counts and all patients have seen a shrinkage in tumor. Now mind you, not all of them are classified as responses, but patients have seen a shrinkage in their tumor size has given us a high level of confidence that the trial should be expanded. And this is what we're doing.

當然，現在我們提供的數據的分母很小，但事實上所有患者的癌症數都顯著下降，所有患者的腫瘤都縮小了。現在請注意，並非所有這些都被歸類為緩解，但患者看到腫瘤尺寸縮小，這讓我們對應該擴大試驗充滿信心。這就是我們正在做的事情。

So, we have enrolled, I believe, around 30 patients in a randomized trial now. That data is maturing. And as the data matures and we confirm the results from the smaller denominator of the initial patients, then I think we will have reason to go to the FDA and ask them for the requirements for a potential accelerated approval for this indication. Now we have also, as our colleagues may have said before, other indications that are potentially, potentially indications that we will go for approval.

因此，我相信我們現在已經招募了大約 30 名患者參加隨機試驗。這些數據正在成熟。隨著數據的成熟，並且我們確認了初始患者的較小分母的結果，那麼我認為我們將有理由去 FDA 詢問他們對該適應症的潛在加速批准的要求。現在，正如我們的同事之前可能說過的那樣，我們還有其他潛在的跡象表明我們將尋求批准。

One is, again, all of these will be subject to expansion of our trials to confirm the initial results from a smaller denominator. But the smaller denominator results are so compelling that, for example, in lung cancer and EGFR mutant patients, we will investigate. In fact, there's a subset of a specific EGFR mutation that we will expand that cohort to understand and verify the profound reduction in tumor size that we have seen in our earlier trials. So that will be similar to what J&J did for a larger patient population with their bispecific.

其一，所有這些都將需要擴大我們的試驗，以確認較小分母的初步結果。但較小的分母結果非常引人注目，例如，我們將在肺癌和 EGFR 突變患者中進行研究。事實上，有一個特定 EGFR 突變的子集，我們將擴展該隊列，以了解和驗證我們在早期試驗中看到的腫瘤大小的顯著減少。因此，這將類似於強生公司利用其雙特異性抗體對更大的患者群體所做的事情。

And the last report that I saw is for a patient population that is about a tenth of the size of what we may be pursuing, the estimates for their product is in the billions in sales. So there are opportunities that we will pursue that are driven by small trials, very specific patient populations that will yield very high response rates and typically de facto biomarker-driven identification of these patient populations. And that applies to lung cancer, certain subsets of lung cancer, and that applies also in a different format for the neoadjuvant.

我看到的最後一份報告針對的患者群體大約是我們可能追求的患者群體的十分之一，他們的產品的銷售額估計為數十億美元。因此，我們將尋求一些由小型試驗、非常特定的患者群體驅動的機會，這些試驗將產生非常高的反應率，並且通常對這些患者群體進行事實上的生物標記驅動的識別。這適用於肺癌、肺癌的某些亞型，也適用於新輔助治療的不同形式。

And in this particular case, what we have seen in our neoadjuvant trial is a surgery sparing. And when we talk about surgery sparing, we're talking about surgeries that would be debilitating for the patient. Removal of the rectum is a debilitating outcome, particularly in the younger patient population, particularly. I mean, it's debilitating for all patients. But if you're in your 20s and 30s and you have a lower colon -- lower left colon tumor that is closest to the rectum and that's going to yield a radical surgery, that would be horrible.

在這個特殊案例中，我們在新輔助試驗中看到的是保留手術。當我們談論手術保留時，我們談論的是會使患者衰弱的手術。切除直腸是一種使人衰弱的結果，尤其是在年輕患者群體中。我的意思是，這會讓所有患者變得虛弱。但如果你在 20 多歲和 30 多歲的時候，你有一個下結腸——最接近直腸的左下結腸腫瘤，而這將導致根治性手術，那將是可怕的。

So if we can prevent that with our neoadjuvant strategy, we believe that's a tremendous opportunity. So we're looking at all of these options and more, of course, and stay tuned.

因此，如果我們能夠透過新輔助策略來預防這種情況，我們相信這是一個巨大的機會。因此，我們正在研究所有這些選項，當然還有更多選項，敬請期待。

That's very helpful. Thank you. One really quick follow-up if I can, just on the neoadjuvant -- the next neoadjuvant setting study. Will that allow for the potential to skip surgery altogether or will all of those patients proceed to surgery?

這非常有幫助。謝謝。如果可以的話，我會進行一次非常快速的隨訪，只是關於新輔助治療——下一個新輔助治療設置研究。這是否有可能完全跳過手術，還是所有這些患者都會接受手術？

Well, okay. So I'll let Dr. O'Day elaborate, but I know at least one patient, after a complete response, refused to have surgery. Now of course, that's a tricky situation because of the ethical considerations, which we don't have an approved product in that indication yet. And hence, that recommendation cannot be made by a physician for ethical reasons right now, right now. But if a patient refuses to have surgery, it's their prerogative. It's their life. So -- but you are seeing that kind of a potential develop.

哦，那好吧。所以我會讓奧戴醫生詳細說明，但我知道至少有一名患者在完全緩解後拒絕接受手術。當然，由於道德方面的考慮，這是一個棘手的情況，我們還沒有針對該適應症的批准產品。因此，出於道德原因，醫生現在不能提出該建議。但如果病人拒絕手術，那是他們的特權。這是他們的生活。所以——但是你看到了這種潛力的發展。

And of course, I want to stress the fact that everything has to be done properly with appropriate regulatory guidance and everything has to be done in an ethical way so that we don't jeopardize the well-being of patients.

當然，我想強調這樣一個事實：一切都必須在適當的監管指導下正確完成，並且一切都必須以道德的方式完成，這樣我們才不會危及患者的福祉。

Great. Thank you for taking our questions.

偉大的。感謝您接受我們的提問。

Matthew Phipps, William Blair.

馬修·菲普斯，威廉·布萊爾。

Hi. Thanks for taking my questions. So just curious, when you said data in the second half from the Phase 2 colorectal study, do you think you'll have PFS data by that point? It seems like given the poor prognosis of patients, that could be possible.

你好。感謝您回答我的問題。所以只是好奇，當您提到第二階段結直腸研究下半年的數據時，您認為到那時您會獲得 PFS 數據嗎？考慮到患者的預後不良，這似乎是可能的。

So I will defer it to our regulatory experts, but PFS in these patients relative to OS in such a short interval of difference that I think OS is the gold standard, PFS is much less so.

因此，我會將其交給我們的監管專家，但這些患者的 PFS 相對於 OS 的差異如此之短，我認為 OS 是黃金標準，PFS 則要差得多。

Steven, Todd, do you have any comments on that?

史蒂文、托德，你們對此有什麼評論嗎？

Yes, I mean, Matt --

是的，我是說，馬特--

Steven --

史蒂文--

(inaudible) Todd

（聽不清楚）托德

No, Steven. Go ahead and I'll --

不，史蒂文。繼續吧，我會--

Okay. Matt, yes. I mean, obviously, we'll have response rate, duration response, PFS, and preliminary survival in these patients as they mature over the course of the year from their last -- from when they were accrued. So obviously, it's a composite endpoint. But to Garo's point, clearly, response and duration of response is what drives -- and prolonged stable disease drive the survival curve. So our primary endpoints are obviously response, duration response, and then ultimately, the gold standard survival.

好的。馬特，是的。我的意思是，很明顯，我們將獲得這些患者的緩解率、緩解持續時間、PFS 和初步生存率，因為他們在從上一次（從他們累積時）開始的一年內成熟。顯然，這是一個複合端點。但就加羅的觀點而言，顯然，反應和反應持續時間才是驅動因素，而長期穩定的疾病驅動著生存曲線。因此，我們的主要終點顯然是反應、持續時間反應，最後是黃金標準生存。

Thanks, Steven. And I guess just curious, Garo, why not disclose at least some indication of the top-line results, I guess, in May given the six-months follow-up by that point? Why wait until after you meet with the FDA to at least I guess say whether or not, you know, or our endpoint has been met or something like that?

謝謝，史蒂文。我想只是好奇，加羅，考慮到當時已經有六個月的後續行動，我想，為什麼不至少在 5 月披露一些頂線結果的跡象呢？為什麼要等到你與 FDA 會面後至少我猜說我們的終點是否已經達到或類似的事情？

It's strictly regulatory courtesy. I think it would be not appropriate if we're ready to present that data to the FDA to make that public right before our FDA meeting.

這是嚴格的監管禮貌。我認為，如果我們準備在 FDA 會議之前向 FDA 提交這些數據並公開這些數據，那是不合適的。

Okay. And I assume then you'll make disclosures publicly after receiving the minutes from that FDA meeting, so adding a bit of time for that.

好的。我想你會在收到 FDA 會議記錄後公開披露信息，所以為此增加了一些時間。

That's right.

這是正確的。

Okay. Thank you.

好的。謝謝。

Kelly Shi, Jefferies.

施凱莉，傑弗里斯。

Hi. Good morning. This is Clara on for Kelly. Thanks for taking my question. So one quick question on non-small cell lung cancer. So for the next update, given you've shown 56% overall response data in nine patients --

你好。早安.這是克拉拉為凱利代言的。感謝您提出我的問題。這是一個關於非小細胞肺癌的快速問題。因此，對於下一次更新，鑑於您已顯示 9 名患者的整體緩解率數據為 56%--

Kelly, you know, your voice is coming very faint and there's some crackling in the line. If you can speak closer to the microphone?

凱利，你知道，你的聲音非常微弱，線路中還有些劈啪聲。如果你能靠近麥克風說話嗎？

How about now?

現在怎麼樣？

Yes, better.

是的，更好。

Okay. Got it. So just one question on the lung cancer update. Given you've shown 50% overall response data in nine patients, wondering what would be the efficacy you need to see on the next update to advance the program into the next stage of development.

好的。知道了。那麼只有一個關於肺癌更新的問題。鑑於您已在 9 名患者中顯示了 50% 的整體緩解數據，想知道您需要在下一次更新中看到什麼功效才能將程序推進到下一開發階段。

And if so, what would be the going-forward plan for lung cancer? And also, just wondering, you know, can you remind us what other data disclosure we should expect in 2024? I believe the BMS partner TIGIT data is also expected this year as well. Just wanted to confirm it. Thank you.

如果是這樣，肺癌的未來計畫是什麼？另外，我想知道，您能否提醒我們 2024 年還應該揭露哪些其他數據？我相信BMS合作夥伴TIGIT的數據今年也有望實現。只是想確認一下。謝謝。

Sure. So a couple of things here. On the lung cancer, as you know, we slowed down overall enrollment in the trial. So what we're doing right now, having dissected the data and looked at subsets of patients that have had significant responses.

當然。這裡有幾件事。如您所知，在肺癌方面，我們放慢了試驗的整體入組速度。所以我們現在正在做的事情是，剖析數據並研究有顯著反應的患者子集。

When I say significant response, I'm talking about complete responses -- rapid complete responses at our low dose level. That, to us, is a significant outcome. So we're in the process of now defining how we would proceed, as I said earlier, with those subsets of biomarker-identifiable patients. And so that's our next step in lung cancer, but that's going to happen very quickly.

當我說顯著反應時，我指的是完全反應——在低劑量水平下快速完全反應。對我們來說，這是一個重大成果。因此，正如我之前所說，我們現在正在確定如何處理那些可透過生物標記識別的患者子集。這就是我們在肺癌方面的下一步，但這將會很快發生。

With regard to data for the balance of this year, we have data coming -- mature data coming from larger cohorts of pancreatic cancer patients in a randomized trial. That would be some time -- maybe preliminary data will be by mid-year, but more mature data by the year-end. We'll have more mature data on melanoma. We will provide the sustainability of responses in sarcoma. And of course, you will see substantially more data in colon cancer shortly after our regulatory meetings.

關於今年剩餘時間的數據，我們有數據即將到來——來自一項隨機試驗中更大的胰腺癌患者隊列的成熟數據。這需要一段時間——也許初步數據將在年中公佈，但更成熟的數據將在年底公佈。我們將獲得有關黑色素瘤的更成熟的數據。我們將提供肉瘤反應的可持續性。當然，在我們的監管會議結束後不久，您將看到更多關於結腸癌的數據。

Thank you, super helpful.

謝謝你，超級有幫助。

And there are no further questions at this time. I would like to turn the conference over to Garo Armen for closing remarks.

目前沒有其他問題。我想請加羅·阿曼 (Garo Armen) 致閉幕詞。

Thank you very much, Audra, and thank you very much for your attentiveness and for the fantastic questions actually. And I think we've covered a great deal here. And I just want to make sure that our stakeholders are ensured of our commitment to make sure that we stayed -- we stay focused, first of all, because we're in a very unique environment where the resources are not as abundant as they were in the past. And so that -- maybe that's a good thing because it forces companies, not just us, but the industry to do things more rationally.

非常感謝你，奧德拉，非常感謝你的細心和實際上提出的精彩問題。我認為我們已經在這裡討論了很多內容。我只是想確保我們的利害關係人能夠兌現我們的承諾，確保我們留下來——首先，我們保持專注，因為我們處於一個非常獨特的環境中，資源並不像以前那麼豐富在過去。所以——也許這是一件好事，因為它迫使公司，不僅僅是我們，而是整個產業更理性地做事。

So we intend on delivering outcomes with efficiency. We are poised to be able to potentially launch products, both from a CMC perspective, as well as from a commercial perspective. We have a terrific team in each category to do this.

因此，我們打算有效率地交付成果。我們準備好能夠從 CMC 角度以及商業角度推出產品。我們在每個類別都有一支出色的團隊來做到這一點。

In addition to that, we have assembled a very, very competent medical affairs team so that we can drive our processes through education, education of the system, patients, regulators, as well as physicians that will eventually prescribe our medicines.

除此之外，我們還組建了一支非常非常有能力的醫療事務團隊，以便我們可以透過教育、系統教育、患者、監管機構以及最終為我們開藥的醫生來推動我們的流程。

So we are attending to all of these very important components. We are a small, large company in that sense and an old, young company in many ways. But thank you very much for your attentiveness, and we will communicate with you appropriately at the next time.

因此，我們正在關注所有這些非常重要的組成部分。從這個意義上說，我們是一家小而大的公司，從很多方面來說，我們都是一家古老而年輕的公司。但非常感謝您的關注，我們下次會適當地與您溝通。

And this concludes today's conference call. Thank you for your participation. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。