Affimed NV (AFMD) 2024 Q3 法說會逐字稿

Good day, everyone, and welcome to Affimed's third-quarter 2024 earnings and corporate update call. (Operator Instructions) As a reminder, today's conference call is being recorded. I would now like to introduce you to your host for today's call, Alex Fudukidis, Head of Investor Relations at Affimed. Please go ahead.

大家好，歡迎參加 Affimed 2024 年第三季財報和公司更新電話會議。（操作員指示）提醒一下，今天的電話會議正在錄音。現在，我想向您介紹今天電話會議的主持人，Affimed 投資者關係主管 Alex Fudukidis。請繼續。

Thank you, Lisa, and thank you all for joining us today for our third quarter 2024 business and financial update call. Before we begin, I'd like to remind everyone that we posted the relevant press release and presentation we will be using today on the Investor Relations section of our website. On the call today, we have members of our management team, including Shawn Leland, our Chief Executive Officer; Andreas Harstrick, our Chief Medical Officer; Wolfgang Fischer, our Chief Operating Officer; Denise Mueller, our Chief Business Officer; and Harry Welten, our Consulting Chief Financial Officer. Our financials today will be presented by our VP of Finance, Michael Wolf.

謝謝你，麗莎，也謝謝大家今天參加我們的 2024 年第三季業務和財務更新電話會議。在我們開始之前，我想提醒大家，我們已在我們網站的投資者關係部分發布了今天將使用的相關新聞稿和簡報。今天的電話會議由我們的管理團隊成員參加，包括執行長 Shawn Leland；我們的首席醫療官 Andreas Harstrick；我們的營運長 Wolfgang Fischer；我們的首席商務官 Denise Mueller；以及我們的諮詢財務長 Harry Welten。我們的財務副總裁 Michael Wolf 將今天的財務報表提交給我們。

The team will be available for Q&A after the prepared remarks. Before we start, I'd like to remind you that today's presentation contains projections and forward-looking statements regarding future events. These statements represent our beliefs and assumptions only as of the date of this call. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

團隊將在準備好的發言後進行問答。在我們開始之前，我想提醒您，今天的演示包含對未來事件的預測和前瞻性陳述。這些聲明僅代表我們截至本次電話會議之日的信念和假設。除法律要求外，我們不承擔公開更新這些前瞻性聲明或更新實際結果可能與前瞻性聲明中預期的結果存在重大差異的原因的義務，即使將來出現新的資訊。

These forward-looking statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in these statements due to various factors, including, but not limited to, those identified under the section entitled Risk Factors in our filings with the SEC and those identified under the section entitled Forward-Looking Statements in the press release that we issued today and filed with the SEC. With that, I'll turn the call over to Shawn. Shawn?

這些前瞻性陳述受到風險和不確定性的影響，實際結果可能由於各種因素而與這些陳述中表達或暗示的結果存在重大差異，包括但不限於我們向美國證券交易委員會提交的文件中題為“風險因素”的部分下所確定的因素以及我們今天發布並向美國證券交易委員會提交的新聞稿中題為“前瞻性陳述”的部分下所確定的因素。說完這些，我會把電話轉給肖恩。肖恩？

Good morning, everyone. Thank you for joining us today. I've been with the company for a couple of months now. And during this time, I've had the chance to immerse myself in the incredible work that is being done at Affimed. I am genuinely impressed by both the groundbreaking science and the clinical milestones our team has achieved over the last 12 months.

大家早安。感謝您今天加入我們。我已經在這家公司工作幾個月了。在此期間，我有機會全心投入 Affimed 所做的令人難以置信的工作。我們團隊在過去 12 個月中取得的突破性科學和臨床里程碑令我印象深刻。

The depth of expertise within our organization and the potential of our platform are truly remarkable, and they have only deepened my confidence in the work that is being done at the company. The main reason I decided to join Affimed was the data demonstrating clinical proof of concept across three different assets spanning solid tumors and hematologic malignancies. Our therapies have shown activity in both monotherapy and combination studies. All of our innate cell engagers are moving well beyond clinical proof of concept, which is having an impact on how we shape and focus the company for the future.

我們組織內的專業知識深度和平台的潛力確實非常出色，它們只會加深我對公司正在進行的工作的信心。我決定加入 Affimed 的主要原因是其數據證明了涵蓋實體腫瘤和血液系統惡性腫瘤的三種不同資產的臨床概念驗證。我們的療法在單一療法和聯合研究中均表現出活性。我們所有的先天細胞參與者都遠遠超出了臨床概念驗證的範圍，這對我們如何塑造和關注公司的未來產生了影響。

Affimed's innovation is bringing meaningful benefits to patients who have often exhausted all other therapeutic options in indications where there are significant unmet medical needs. In addition to the promising activity shown with our innate cell engagers, both as monotherapy and in combination, they have also demonstrated a favorable and differentiated safety profile even in these challenging and heavily pretreated patient populations, many of whom are in the end stage of their disease. The fact that we continue to observe meaningful and often durable responses gives us immense confidence. These results are what excite me the most about our platform and therapies, which offer hope where little has existed before.

Affimed 的創新為那些在存在嚴重未滿足的醫療需求的情況下往往已經用盡所有其他治療選擇的患者帶來了有意義的益處。我們的先天細胞接合劑除了作為單一療法和聯合療法表現出良好的活性外，即使在這些具有挑戰性且接受過大量治療的患者群體中也表現出良好且差異化的安全性，其中許多患者已處於疾病的終末階段。事實上，我們不斷觀察到有意義且往往持久的反應，這給了我們極大的信心。這些結果讓我對我們的平台和療法感到最興奮，它們為以前幾乎不存在的領域帶來了希望。

I'd like to highlight the differentiated safety profile of our NK cell engagers, which enables us to target molecules with a narrow therapeutic index due to their tumor specificity. NK cells naturally distinguish between tumor and healthy tissue. So when targeting CD123, for instance, our engager binds to normal tissue, but does not trigger NK cell killing due to inhibitory factors in healthy cells. This leads to a safer profile and improved therapeutic index for our CD123 engager, AFM28, compared to TCEs, ADCs and CAR-T, which have toxicities that are often unmanageable and sometimes fatal.

我想強調一下我們的 NK 細胞接合劑的差異化安全性，這使我們能夠針對由於其腫瘤特異性而具有較窄治療指數的分子。NK 細胞自然地區分腫瘤和健康組織。因此，當以 CD123 為目標時，我們的接合劑會與正常組織結合，但不會因為健康細胞中的抑制因素而觸發 NK 細胞殺傷。與 TCE、ADC 和 CAR-T 相比，這使得我們的 CD123 接合器 AFM28 具有更安全的特性和更高的治療指數，而 TCE、ADC 和 CAR-T 的毒性通常難以控制，有時甚至是致命的。

Although we observed some toxicity with AFM28, these events are fewer and manageable. This tumor specificity is also seen with AFM24, our EGFR engager, which avoids the skin and mucosal toxicities associated with other EGFR targeting approaches, further underscores the unique safety advantages of our NK cell engagers. Today's call will be brief as our key clinical updates will be shared in December. At the upcoming ASH 2024 conference, we are excited to have an oral presentation on AFM28 as well as preclinical data at a poster session.

儘管我們觀察到 AFM28 有一些毒性，但這些事件較少且易於控制。我們的 EGFR 接合器 AFM24 也具有這種腫瘤特異性，它避免了與其他 EGFR 標靶方法相關的皮膚和黏膜毒性，進一步凸顯了我們的 NK 細胞接合器獨特的安全優勢。今天的電話會議將很簡短，因為我們的主要臨床更新將在 12 月分享。在即將舉行的 ASH 2024 會議上，我們很高興能在海報展示會上就 AFM28 進行口頭報告並展示臨床前數據。

Data from our LuminICE-203 trial will also be presented at a poster session. Clearly, this recognition is based on the strength of our data. This is not only exciting, it is validating that our innate cell engagers may have a key role in the future paradigm. On December 17, we will host a company conference call to provide a clinical update on AFM24. I'd like to take a moment now to reflect on what we have been doing since we last spoke.

我們的 LuminICE-203 試驗數據也將在海報展示會上展示。顯然，這種認可是基於我們數據的實力。這不僅令人興奮，而且還證實了我們先天的細胞參與者可能在未來的範式中發揮關鍵作用。12 月 17 日，我們將召開公司電話會議，提供有關 AFM24 的臨床最新進展。現在我想花一點時間來回顧一下自從我們上次談話以來我們都做了些什麼。

Since joining, I've hit the ground running, speaking with members of the financial community, potential partners, KOLs and many of our clinical investigators to gain their perspectives on the value they see in our therapies and how they would like to see us continue their development. I'm taking this feedback very seriously and used it to further refine our strategy and our focus. We will maintain our focus on clinical development priorities. Our decisions about our programs will be based on clinical benchmarks, the competitive landscape and the commercial potential.

自從加入以來，我立即投入工作，與金融界成員、潛在合作夥伴、KOL 以及我們的許多臨床研究人員進行交談，以了解他們對我們的療法的價值的看法，以及他們希望我們如何繼續發展。我非常重視這些回饋，並利用它來進一步完善我們的策略和重點。我們將繼續關注臨床開發重點。我們對專案的決定將基於臨床基準、競爭格局和商業潛力。

Our goal going forward will be to deliver therapies that not only demonstrate strong clinical efficacy, but also have a meaningful impact on the treatment paradigm and are commercially sustainable. In addition, we understand that partnerships will play a pivotal role in accelerating our progress. Drawing on my extensive background in business development, we are pursuing a wider range of potential collaborations. Broadening our thinking on the types of collaborations will allow us to engage with a more diverse set of potential partners and further expand our strategic options. Affimed today is a more streamlined and focused organization.

我們未來的目標是提供不僅具有強大臨床療效，而且對治療模式產生重大影響並具有商業可持續性的治療方法。此外，我們知道合作夥伴關係將在加速我們的進步中發揮關鍵作用。憑藉我在業務發展方面的豐富背景，我們正在尋求更廣泛的潛在合作。拓寬合作類型的思維將使我們能夠與更多樣化的潛在合作夥伴接觸，並進一步擴大我們的策略選擇。如今，Affimed 已成為一個更精簡、更專注的組織。

As we take our company into the future, I'm committed to delivering differentiated clinical data from our ongoing trials and ensuring steady, measurable progress across our programs. I reiterate my commitment to improving the financial health of our company, and we are actively working on cementing our financial position. My number one objective is to ensure that our company is well capitalized to deliver on the expectations we have heard from the financial community and our investigators in order for us to continue to further the clinical development of our programs and ensure the long-term success of our company. This will enable us to evolve the company such that we not only develop innovative therapies, but we operate in a way that maximizes value for all stakeholders.

隨著我們公司走向未來，我致力於從我們正在進行的試驗中提供差異化的臨床數據，並確保我們整個計畫取得穩定、可衡量的進展。我重申我致力於改善公司財務狀況的承諾，我們正在積極努力鞏固我們的財務狀況。我的首要目標是確保我們公司擁有充足的資本，以滿足金融界和研究人員對我們的期望，以便我們可以繼續推進我們專案的臨床開發，並確保我們公司的長期成功。這將使我們能夠發展公司，使我們不僅能夠開發創新療法，而且能夠以最大化所有利害關係人價值的方式運作。

That includes our investors, our partners and most importantly, the patients who depend upon us. With that, I'll pass the call to Andreas to give you an update on our clinical trial progress.

其中包括我們的投資者、我們的合作夥伴，最重要的是，依賴我們的病人。說完這些，我會把電話轉給安德烈亞斯，讓他向你通報我們的臨床試驗的進度。

Yes. Thank you, Shawn, and welcome to everybody on the line. As Shawn mentioned, our clinical update today will be brief with significant updates to come at the ASH 2024 meeting in December. These ASH presentations include data from our hematological trials, namely LuminICE-203, the combination trial with Acimtamig and AlloNK cells in refractory Hodgkin lymphoma and for AFM28, our CD123 targeting ICE for acute myeloid leukemia. As mentioned, for our EGFR targeting ICE AFM24, we will have a dedicated conference call to discuss the progress in the non-small cell lung cancer EGFR wild-type cohort on December 17.

是的。謝謝你，肖恩，歡迎大家來線。正如肖恩所提到的，我們今天的臨床更新將很簡短，重大更新將在 12 月的 ASH 2024 會議上發布。這些 ASH 報告包括我們血液學試驗的數據，即 LuminICE-203（針對難治性霍奇金淋巴瘤的 Acimtamig 和 AlloNK 細胞聯合試驗）和 AFM28（針對急性髓細胞白血病的 CD123 靶向 ICE）。如上所述，對於我們的EGFR靶向ICE AFM24，我們將於12月17日召開專門的電話會議，討論非小細胞肺癌EGFR野生型隊列的進展。

That said, we have made important strides across our clinical programs this quarter, and I'd like to briefly highlight where we stand today. Let's start with our AFM24-102 trial, as shown on Slide 4, in which we are evaluating AFM24 in combination with atezolizumab in non-small cell lung cancer patients who have exhausted standard of care options. Both the EGFR wild-type and EGFR mutant cohorts are now fully enrolled, and we are actively treating and monitoring patients. And as a reminder, we previously reported data for 17 patients from the wild-type cohort at ASCO 2024.

儘管如此，本季度我們在臨床計畫中取得了重要進展，我想簡要介紹一下我們目前的狀況。讓我們從 AFM24-102 試驗開始，如幻燈片 4 所示，我們正在評估 AFM24 與阿特珠單抗聯合治療已經用盡標準治療方案的非小細胞肺癌患者。EGFR野生型和EGFR突變型隊列現在都已完全招募，我們正在積極治療和監測患者。提醒一下，我們之前曾在 ASCO 2024 上報告過 17 位野生型患者的資料。

Four confirmed objective responses were seen, 1 complete response and 3 partial responses. In addition, 8 patients achieved stable disease resulting in a disease control rate of 71%. Median progression-free survival at that time was 5.9 months with a median follow-up of 7.4 months. Importantly, at the time of data cut, 3 of 4 responses were ongoing for more than 7 months, and all responding patients had a documented progression while receiving checkpoint inhibitor treatment before, which supports the hypothesis that combining AFM24 with atezolizumab may provide an alternative strategy to overcome resistance to existing therapies.

已觀察到 4 次確認的客觀反應，1 次完全反應和 3 次部分反應。此外，8名患者病情穩定，疾病控制率為71%。當時的中位無惡化存活期為 5.9 個月，中位追蹤期為 7.4 個月。重要的是，在數據截止時，4 個反應中有 3 個持續了 7 個多月，並且所有反應患者在先前接受檢查點抑制劑治療時均有記錄的進展，這支持了以下假設：將 AFM24 與阿替利珠單抗相結合可能提供克服現有療法抗藥性的替代策略。

For the AFM24 non-small cell lung cancer EGFR mutant cohort, we presented early efficacy data on our Q2 earnings call with also 4 objective responses seen in the initial 17 patients. We anticipate to report the final response and safety data from the non-small cell lung cancer EGFR wild-type cohort on our December 17 company conference call. Final PFS data from the EGFR wild-type and overall response and PFS data from the EGFR mutant cohorts are expected to be presented at a major scientific conference in the first half of 2025. We believe that the data of AFM24 in combination with a PD-1 targeting checkpoint inhibitor, while early, demonstrate promising activity in treatment refractory non-small cell lung cancer patients, potentially offering a chemotherapy-free alternative for these patients who have failed multiple lines of treatment, a notable advantage, given the difficulties these patients have in tolerating additional chemotherapy.

對於 AFM24 非小細胞肺癌 EGFR 突變群，我們在第二季收益電話會議上展示了早期療效數據，並且在最初的 17 名患者中也觀察到了 4 個客觀反應。我們預計將在 12 月 17 日的公司電話會議上報告非小細胞肺癌 EGFR 野生型隊列的最終反應和安全性數據。EGFR野生型和整體反應的最終 PFS 數據以及 EGFR 突變型隊列的 PFS 數據預計將在 2025 年上半年的大型科學會議上發表。我們認為，AFM24 與 PD-1 標靶檢查點抑制劑聯合使用的數據雖然還處於早期階段，但已顯示出對治療難治性非小細胞肺癌患者有希望的活性，可能為這些多種治療失敗的患者提供無化療的替代方案，考慮到這些患者在耐受額外化療方面的困難，這是一個顯著的優勢。

Moving to our Acimtamig program, as shown on Slide 6. In the LuminICE study, where we are combining AlloNK and our CD30 targeting ICE, Acimtamig, we are progressing this study for patients with multi-refractory Hodgkin lymphoma. We announced that clinical data from the 4 cohorts of the run-in phase, which are all fully recruited now, will be presented at ASH 2024. Finally, we also announced that our AFM28 program targeting CD123 for relapsed/refractory AML will be featured in an oral presentation at ASH.

前往我們的 Acimtamig 程序，如幻燈片 6 所示。在 LuminICE 研究中，我們將 AlloNK 與針對 CD30 的 ICE Acimtamig 結合起來，針對多重難治性霍奇金淋巴瘤患者進行這項研究。我們宣布，導入期 4 個隊列的臨床數據將在 ASH 2024 上公佈，這些隊列目前已全部招募完畢。最後，我們也宣布，針對復發/難治性 AML 的 CD123 的 AFM28 計畫將在 ASH 上進行口頭報告。

The ongoing Phase I trial of AFM28 monotherapy has escalated dosing through six cohorts, reaching 300 milligrams weekly. No dose-limiting toxicities have been observed at this dose level. Based on the promising monotherapy results reported during our Q2 earnings call, we have further expanded Cohort 6 and added additional six patients to confirm the observed monotherapy signal. The ASH 2024 presentation will feature updated data from this study.

正在進行的 AFM28 單藥治療 I 期試驗已透過 6 個隊列增加劑量，達到每週 300 毫克。在此劑量水平下沒有觀察到劑量限制性毒性。根據我們在第二季度收益電話會議上報告的有希望的單一療法結果，我們進一步擴大了第 6 組並增加了另外六名患者以確認觀察到的單一療法信號。ASH 2024 演示將展示該研究的最新數據。

With that, I'll conclude our clinical program update and now hand it over to Michael Wolf for a review of our financials. Michael, please?

至此，我將結束我們的臨床計劃更新，現在將其交給邁克爾沃爾夫以審查我們的財務狀況。請問麥可嗎？

Thank you, Andreas. Balance sheet and income statement highlights are shown on Slides 10 and 11 of the presentation. A quick reminder that Affimed's consolidated financial statements have been prepared in accordance with IFRS as issued by the International Accounting Standard Board or IASB. The consolidated financial statements are prepared in euros. Since our financials are described in detail in the press release we issued this morning, I will only provide highlights on this call.

謝謝你，安德烈亞斯。資產負債表和損益表重點顯示在簡報的第 10 和 11 張投影片中。快速提醒一下，Affimed 的合併財務報表是根據國際會計準則委員會或 IASB 發布的 IFRS 編制的。合併財務報表以歐元編製。由於我們的財務狀況在今天早上發布的新聞稿中有詳細描述，因此我將僅在本次電話會議上提供重點內容。

We ended the third quarter with cash, cash equivalents and investments of EUR24.1 million compared to EUR72 million on December 31, 2023. Based on our current operating and budget assumptions, we anticipate that our cash and cash equivalents and investments, together with anticipated proceeds from the ATM program and the sale of AbCheck will finance us into the fourth quarter of 2025. Net cash used in operating activities for the quarter ended September 30, 2024, was EUR11.1 million compared to EUR18.3 million for the quarter ended September 30, 2023. Total revenue for the quarter ended September 30, 2024, was EUR0.2 million compared with EUR2 million for the quarter ended September 30, 2023.

截至第三季度，我們的現金、現金等價物和投資為 2,410 萬歐元，而 2023 年 12 月 31 日為 7,200 萬歐元。根據我們目前的營運和預算假設，我們預計我們的現金和現金等價物和投資，加上 ATM 計劃和 AbCheck 出售的預期收益將為我們到 2025 年第四季提供資金。截至 2024 年 9 月 30 日的季度，經營活動所用淨現金為 1,110 萬歐元，而截至 2023 年 9 月 30 日的季度為 1,830 萬歐元。截至 2024 年 9 月 30 日的季度總收入為 20 萬歐元，而截至 2023 年 9 月 30 日的季度總收入為 200 萬歐元。

R&D expenses for the quarter ended September 30, 2024, were EUR10.1 million compared to EUR21.5 million in 2023. G&A expenses for the quarter ended September 30, 2024, were EUR4.3 million compared to EUR5.4 million for the quarter ended September 30, 2023. Net loss for the quarter ended September 30, 2024, was EUR15.1 million or a loss of EUR0.94 per common share compared with a net loss of EUR24.4 million or a loss of EUR1.63 per common share for the quarter ended September 30, 2023. Now I'll turn the call back to Shawn for final remarks. Shawn?

截至 2024 年 9 月 30 日的季度研發費用為 1,010 萬歐元，而 2023 年為 2,150 萬歐元。截至 2024 年 9 月 30 日的季度的 G&A 費用為 430 萬歐元，而截至 2023 年 9 月 30 日的季度的 G&A 費用為 540 萬歐元。截至 2024 年 9 月 30 日的季度淨虧損為 1,510 萬歐元，或每股普通股虧損 0.94 歐元，而截至 2023 年 9 月 30 日的季度淨虧損為 2,440 萬歐元，或每股普通股虧損 1.63 歐元。現在我將電話轉回給肖恩，請他做最後的演講。肖恩？

Thank you, Michael. In the couple of months since I joined Affimed, I've been deeply impressed by the dedication of our team and the meaningful progress we are making. Our therapies are treating patients who have exhausted other options, and we remain committed to advancing innovative treatments that address urgent unmet needs. Looking ahead, we will focus on advancing our key clinical programs, broadening partnerships and maintaining financial stability. We believe these efforts will maximize the impact of our science and create value for all stakeholders.

謝謝你，麥可。在加入 Affimed 的幾個月裡，我們團隊的奉獻精神和所取得的重大進展給我留下了深刻的印象。我們的療法正在治療那些已經用盡其他治療選擇的患者，並且我們仍然致力於推進創新治療方法來滿足緊迫的未滿足需求。展望未來，我們將專注於推動我們的關鍵臨床項目、擴大合作夥伴關係並保持財務穩定。我們相信這些努力將最大限度地發揮我們的科學影響力並為所有利益相關者創造價值。

Despite the challenging market environment, I'm confident in our ability to chart the right course forward and secure the capital needed to support our progress. I want to extend my sincere gratitude to our investors for your continued support, to the patients and families who place their trust in us and to our dedicated employees who drive our mission. Together, we will keep pushing forward to deliver life-changing therapies to those who need them most. Thank you for your attention, and we are happy to take any questions. Operator?

儘管市場環境充滿挑戰，但我相信我們有能力規劃正確的前進方向並獲得支持我們進步所需的資金。我要向我們的投資者的持續支持、對我們的信任的患者和家屬以及推動我們完成使命的敬業員工表示誠摯的謝意。我們將共同努力，繼續為最需要的人提供改變生活的治療。感謝您的關注，我們很樂意回答您的任何問題。操作員？

(Operator Instructions) Li Watsek, Cantor Fitzgerald.

（操作員指令） Li Watsek，Cantor Fitzgerald。

Maybe just on AFM28 in terms of the data update at ASH, how much durability should we expect? And in terms of the patients who were enrolled into the study, can you comment on the mutational status in prior treatments?

也許僅就 AFM28 的 ASH 數據更新而言，我們應該期待多少耐用性？對於參與研究的患者，您能否評論一下先前治療中的突變情況？

Li, thanks for your question. Andreas, do you want to respond to Li's question?

李，謝謝你的提問。安德烈亞斯，你想回答李的問題嗎？

Yes. So in terms of durability, obviously, we have 6 patients that we reported at our last earnings call. These patients will have a meaningful observation period or follow-up period to really assess durability of responses. The additional six patients that we added were recruited more recently. And for most of these some patients are still actively receiving treatment. For most of these additional 6 patients, the follow-up period may just be a little bit too short to have meaningful conclusions on duration of responses.

是的。因此就耐用性而言，顯然，我們在上次收益電話會議上報告了 6 名患者。這些患者將有一個有意義的觀察期或追蹤期，以真正評估反應的持久性。我們新增的六名患者是最近招募的。其中大多數患者仍在積極接受治療。對於另外 6 名患者中的大多數來說，追蹤期可能太短，無法就反應持續時間得出有意義的結論。

In terms of pretreatment, 80% of our patients in this trial had been pretreated with a hypomethylating agent and venetoclax. A little over 50%, 55% or so had also pretreatment with an anthracycline, mainly anthracycline Ara-C containing regimen. And I believe roughly 1/3 of our patients had also received a stem cell transplant. In terms of mutational status, if you look at negative mutations like RUNX1 or p53, roughly 2/3 of these patients have a negative molecular profile in terms of negative predicting mutations.

在預治療方面，本次試驗中 80% 的患者已接受過低甲基化藥物和維奈克拉的預先治療。略高於50%、約55%的患者也曾接受過蒽環類藥物（主要為含蒽環類藥物 Ara-C 的方案）的預先治療。我相信我們大約三分之一的患者也接受了幹細胞移植。就突變狀態而言，如果您觀察 RUNX1 或 p53 等負面突變，大約 2/3 的患者在負面預測突變方面具有負面分子譜。

Okay. Great. And then you mentioned that maybe you guys can have a monotherapy path here. I'm just curious when would you be in a position to go to the FDA to discuss the registrational path here? And what will be the patient population you'll be looking at, given we have other targeted agents approved here?

好的。偉大的。然後您提到也許您可以在這裡採用單一療法。我只是好奇您什麼時候可以去 FDA 討論這裡的註冊途徑？鑑於我們已經批准了其他針對性藥物，那麼您將關注的患者族群是哪些？

Yes. Li, thanks for the follow-up question. Andreas, do you want to respond to Li's follow-up question?

是的。李先生，感謝您的後續提問。安德烈亞斯，你想回答李的後續問題嗎？

Yes. So I think what we announced is that, again, we will have additional patients on the 300 milligrams dose level. The protocol allows us to go even beyond the 12 patients we have now. We are also planning to add at least one higher dose cohort to make sure that we are really capturing the full therapeutic potential in terms of deepness and response and response duration. Again, the safety profile is very safe, so we easily can further dose-escalate. And this will give us a data set that would enable us then to go to FDA a little bit depending on the maturation of the data. And what was your second question? The...

是的。因此我認為，我們再次宣布，我們將有更多患者接受 300 毫克劑量的治療。該協議使我們能夠治療超過目前 12 名患者。我們還計劃增加至少一個更高劑量組，以確保我們真正獲得深度、反應和反應持續時間的全部治療潛力。再次強調，安全性非常安全，因此我們可以輕鬆地進一步增加劑量。這將為我們提供一個數據集，使我們能夠根據數據的成熟度稍微向 FDA 提供資訊。您的第二個問題是什麼？這...

The patient population.

患者群。

Oh, the patient population, yes. Again, this is a very well-tolerated drug. We have not encountered dose-limiting toxicities as a pharmacodynamically active doses like 250, 300. Also, our Phase I study has been open for all patients. So we have no age limitations or anything. So we expect to see patients, if we go down the monotherapy path, that fulfill FDA requirements for a patient population of unmet medical need.

哦，是的，患者人群。再次強調，這是一種耐受性非常好的藥物。我們還沒有遇過像 250、300 這樣藥效動力學活性劑量的劑量限制性毒性。此外，我們的第一階段研究已經向所有患者開放。因此我們沒有年齡限製或其他任何限制。因此，如果我們採用單一療法，我們期望看到患者滿足 ​​FDA 對未滿足醫療需求患者群體的要求。

So depending on agent risk profile, they either should have received and have not responded to an anthracycline Ara-C containing regimen, if they are younger, fitter patients or to a hypomethylating agent plus/minus venetoclax regimen. If they are older patients, or patients who have a targetable mutation like FLT3 or something, they should also have exhausted these specifically targeting therapies to be eligible and to comply with the definition of an unmet medical need population.

因此，根據代理人的風險狀況，如果他們是年輕、身體健康的患者，他們應該接受含蒽環類 Ara-C 的方案治療但對這種方案沒有反應，或者如果他們是低甲基化藥物加/減維奈克拉的方案治療但對這種方案沒有反應。如果他們是年齡較大的患者，或者俱有 FLT3 等可靶向突變的患者，他們也應該用盡這些特定的標靶療法以符合資格並符合未滿足醫療需求人群的定義。

Daina Graybosch, Leerink Partners.

Daina Graybosch，Leerink Partners。

Two for me. First, Shawn, I think I heard you say that you are broadening your thinking on the type of collaborations. And I wonder if you could talk about what you mean. So what type of collaborations was the company pursuing previously? And what does it mean to broaden that? And then I have a follow-up.

對我來說是兩個。首先，肖恩，我想我聽到你說過你正在拓寬對合作類型的思考。我想知道您是否可以談談您的意思。那麼該公司之前尋求過什麼類型的合作？那麼擴大這一範圍意味著什麼呢？然後我有一個後續問題。

Yes, Daina, so thanks for the question. I mean I think kind of given the financial position of the company, I mean, it makes sense to kind of evaluate all potential options that are on the table here. So I mean, I think we're looking at a variety of different strategic partnerships that could exist. These include potential regional deals, for example. I think in the past, the company was more so focused on kind of a very finite set that was specifically looking at kind of multinational partners.

是的，Daina，謝謝你的提問。我的意思是，我認為考慮到公司的財務狀況，評估這裡列出的所有潛在選擇是有意義的。所以我的意思是，我認為我們正在考慮可能存在的各種不同的策略夥伴關係。例如，其中包括潛在的區域交易。我認為，過去公司更注重一種非常有限的集合，特別是尋找跨國合作夥伴。

So we've just broadened that strategy to create additional optionality to bring in additional nondilutive capital that could come into the company. So that's really essentially what we mean by kind of broadening the scope or lens on the BD partnering front. And that's really driven by kind of leveraging kind of my past experience and relationships with companies on the business development front.

因此，我們只是擴大了這個策略，以創造額外的選擇性，從而為公司帶來額外的非稀釋性資本。所以這其實就是我們所說的擴大 BD 合作範圍或視角。這實際上是透過利用我過去的經驗以及與業務發展方面的公司建立的關係來實現的。

Got it. Now a very different question. On AFM24, how are you thinking about potentially the development path going forward? Maybe similar to what Li just asked for AFM28, will you consider different combinations like chemotherapy, TKIs, different PD-1s? And when might you make those decisions?

知道了。現在是一個非常不同的問題。對於 AFM24，您如何看待未來的潛在發展路徑？也許與李剛才要求的 AFM28 類似，您會考慮不同的組合，例如化療、TKI、不同的 PD-1 嗎？您什麼時候會做出這些決定？

Yes. Daina, thanks for the additional follow-up question. Andreas, do you want to respond to Daina's question?

是的。Daina，感謝您提出的附加後續問題。安德烈亞斯，你想回答戴娜的問題嗎？

Yes, sure. So I think the main difference between our hematological indications like treatment refractory Hodgkin lymphoma or treatment refractory AML, we believe that for a large indication like non-small cell lung cancer, it is very unlikely to achieve a regulatory approval with a single-arm noncontrolled trial. FDA historically have always insisted on randomized Phase III trials. Now currently, we are waiting to let the AFM24 atezolizumab or PD-1 data mature both in terms of final response rate, but also in terms of PFS. As you remember, we reported a median PFS of close to 6 months for our initial data set in the EGFR wild-type cohort, which we believe is already quite differentiating from the 4 to maybe 4.5 months that you would see with standard of care.

是的，當然。因此，我認為我們的血液學適應症（如治療難治性霍奇金淋巴瘤或治療難治性 AML）之間的主要區別在於，我們認為對於像非小細胞肺癌這樣的大適應症，透過單臂非對照試驗獲得監管部門批准的可能性很小。FDA 歷史上一直堅持隨機化 III 期試驗。目前，我們正在等待 AFM24 atezolizumab 或 PD-1 數據在最終緩解率和 PFS 方面成熟。您還記得，我們​​報告稱，EGFR野生型隊列的初始數據集的中位 PFS 接近 6 個月，我們認為這與標準治療中的 4 到 4.5 個月已經有很大區別。

And this will give us a couple of optionalities. We could consider to take the doublet into a registration trial against a standard arm, which most likely would be docetaxel, also given the very benign safety profile that we are seeing, and then we have patients now on trial and then continuously drugged for more than 10 or more than 12 months. We can easily also develop triplet combinations where we could add either a VEGF inhibiting moiety like ramucirumab, given the proven synergy between immune modulating therapies and VEGF inhibition or we could add a drug like docetaxel to the doublet. And this would create data sets for an informed decision whether to take a doublet or a triplet into a registration-directed trial.

這將為我們提供一些選擇。我們可以考慮將雙聯療法與標準療法（最有可能的是多西他賽）進行對比，同時考慮到我們看到的非常良性的安全性，然後我們現在讓患者接受試驗，並連續用藥超過 10 個月或 12 個月。我們還可以輕鬆地開發三重療法，其中我們可以添加 VEGF 抑制部分（如雷莫蘆單抗），因為免疫調節療法和 VEGF 抑制之間已證實具有協同作用，或者我們可以將多西他賽等藥物添加到雙聯療法中。這將創建資料集，以便做出明智的決定，是否將雙聯或三聯納入註冊指導試驗。

Kripa Devarakonda, Truist.

Kripa Devarakonda，Truist。

This is Alex Xenakis on for Kripa. Also on AFM24, can you remind us the data expectations for what type of data will be presented in December, like the number of patients and the durability? And then also on the development strategy, I believe that the company said that we'll see a presentation of additional data in the first half of 2025. Do you think you'll have enough data by then to make a go/no-go decision on the forward development of the program?

這是為 Kripa 效力的 Alex Xenakis。另外在 AFM24 上，您能否提醒一下我們對 12 月將呈現哪些類型資料的預期，例如病患數量和耐用性？然後關於發展策略，我相信公司表示我們將在 2025 年上半年看到更多數據的展示。您是否認為到那時您將擁有足夠的數據來對該計劃的未來發展做出是否繼續進行的決定？

Yes, Alex, thanks for the question on behalf of Kripa. Andreas, do you want to respond to Alex's question?

是的，亞歷克斯，我代表 Kripa 感謝你提出這個問題。安德烈亞斯，你想回答亞歷克斯的問題嗎？

Yes. So as we said at our earnings call in December 17, the main focus will be on the EGFR wild-type cohort. As you know, here, we targeted roughly 40 patients. The cohort is fully enrolled. And what will be mature at that point will mainly be the response, the final response rate data. We expect seeing patients on trial that it will take probably another couple of months until we have final PFS data.

是的。因此，正如我們在 12 月 17 日的財報電話會議上所說的那樣，主要關注點將放在 EGFR 野生型群體上。如您所知，我們這裡針對的患者大約有 40 名。該隊列已全部招滿。到那時成熟的主要是響應，即最終的響應率數據。我們預計，接受試驗的患者可能還需要幾個月的時間才能獲得最終的 PFS 數據。

So response and toxicity safety will be the main focus of our company event in December. As we said, major PFS data for the EGFR wild-type cohort may need more time to mature. The same is true for the response data in the EGFR mutant cohort. These patients were enrolled a little bit later, and we said we are targeting 25 patients here.

因此，響應和毒性安全將是我們公司 12 月活動的主要重點。正如我們所說，EGFR野生型隊列的主要 PFS 數據可能需要更多時間才能成熟。EGFR突變隊列中的響應數據也是如此。這些患者招募得稍晚一些，我們的目標是 25 名患者。

And also PFS of the EGFR mutant cohort will need more time to really mature. These data are expected to be displayed at a major scientific conference during the first half of 2025.

而 EGFR 突變群體的 PFS 需要更多時間才能真正成熟。這些數據預計將在2025年上半年的大型科學會議上展出。

Yanan Zhu, Wells Fargo.

朱亞南，富國銀行。

Just to follow up also on AFM24. Have you submitted the abstract for the first half '25 scientific conference? And has it been accepted? Also wondering in terms of the PFS data, ow much longer the PFS needed to be compared with the 4.5 months for RAMY plus proceeds those seeds for the data to be considered as a strong set of data? And then I have a follow-up.

只是為了跟進 AFM24。您提交了 25 年上半年科學會議的摘要嗎？它被接受了嗎？還想知道就 PFS 數據而言，PFS 需要與 RAMY 的 4.5 個月進行比較多長時間，再加上那些種子數據才能被視為一組強有力的數據？然後我有一個後續問題。

Yes, thanks for the initial questions. Andreas, do you want to respond to his questions?

是的，感謝您最初的提問。安德烈亞斯，你想回答他的問題嗎？

Yes. So let's start with the last question. I'm not sure whether I got the first question fully. So what we have reported is 5.9 months median progression-free survival for the EGFR wild-type cohort. For the EGFR mutant cohort, we had not PFS data, but we also reported that out of the 4 responses that we had in the initial 17 patients, all 4 responses were on treatment for 7-plus months, which already gives you an indication that it appears that responses that we are inducing can be very durable.

是的。那我們就從最後一個問題開始。我不確定我是否完全理解了第一個問題。因此，我們報告的是 EGFR 野生型群體的中位無惡化存活期為 5.9 個月。對於 EGFR 突變隊列，我們沒有 PFS 數據，但我們也報告，在最初 17 名患者中獲得的 4 次反應中，所有 4 次反應均經過了 7 個月以上的治療，這已經表明我們誘導的反應似乎可以非常持久。

Now when you consider going into a Phase 3 trial, one important point estimate always is the median progression-free survival. Again, here, we see probably a 1.5 to 2 months difference, which is quite meaningful in these late-line patients. But what also goes into your consideration is the shape of the curve. So we know that chemotherapy usually basically drops down to 0 in their progression-free survival because they are rarely long-term responders to chemotherapy.

現在，當您考慮進入第 3 階段試驗時，一個重要的點估計始終是中位無惡化存活期。再次，我們在這裡看到可能 1.5 到 2 個月的差異，這對於這些晚期患者來說非常有意義。但您還需要考慮的是曲線的形狀。因此我們知道，化療通常會導致患者的無惡化存活期基本上降至 0，因為他們很少對化療有長期反應。

This is different for immune modulating treatments where you usually see a tail or often see a tail of your PFS curve where a meaningful percentage of patients remains progression-free for a prolonged period of time. And this will all go into your estimated hazard ratio, which basically will drive your approval. As I said, we want to let the data from the doublet cohort mature a little bit more. We believe that this may take until early, probably, first quarter 2025.

這與免疫調節治療不同，在免疫調節治療中，您通常會看到尾部或經常看到 PFS 曲線的尾部，其中相當大比例的患者在較長時間內保持無進展狀態。這些都會計入您的預估風險比，從而基本上決定您的批准。正如我所說，我們希望讓雙聯體隊列的數據更加成熟。我們認為這可能要到 2025 年初，可能是第一季。

And then we will be in a position to make an informed decision whether to take the doublet directly into registration-directed trial against, for example, docetaxel. Now the second question, as far as I recall, was whether we have submitted to the scientific conferences already. That would be a little bit too early. Most of the scientific conferences that we consider for the first half of 2025 have their abstract submission deadlines either late December or late January. This is the time when we'll be submitting the data to be presented at the first half of 2025.

然後，我們將能夠做出明智的決定，是否將雙聯藥直接納入針對多西他賽等的註冊導向試驗。現在第二個問題是，據我記得，我們​​是否已經向科學會議提交了提交資料。那可能有點太早了。我們考慮在 2025 年上半年舉行的大多數科學會議的摘要提交截止日期是 12 月下旬或 1 月下旬。這是我們提交 2025 年上半年要呈現的資料的時間。

That's super helpful. Yes, I was wondering also about the long-tail phenomenon and whether that might be possible for the AFM24 plus atezo combo. Thanks for shedding some light on that. A quick follow-up for the Hodgkin lymphoma update. What data could we expect at ASH? Or could we expect to see better response rate or CR rate in Cohorts 3 and 4, given that they had a greater number of NK cells?

這非常有幫助。是的，我也想知道長尾現像以及 AFM24 加 atezo 組合是否可能實現這種現象。感謝您對此的詮釋。快速跟進霍奇金淋巴瘤的最新進展。我們可以在 ASH 上期待哪些數據？或者，考慮到第 3 組和第 4 組的 NK 細胞數量較多，我們是否可以預期看到更好的反應率或 CR 率？

So at ASH, again, we have now fully recruited cohorts. The main focus will be on the initial response rate, given the fact that Cohort 3 and 4 started enrollment only about like 2.5 months ago. And as patients can receive up to 3 cycles, many of these patients are still in active treatment. So it will be an early look at response rate, both overall response rate as well as complete response rate.

因此，在 ASH，我們現在已經全面招募了隊伍。由於第 3 和第 4 組僅在大約 2.5 個月前開始招生，因此主要關注點將放在初始回應率上。由於患者最多可以接受3個週期的治療，因此許多患者仍在接受積極治療。因此，這將是對回應率的早期觀察，包括總體回應率以及完全回應率。

Again, at this point, it's hard to predict or speculate whether the increase in cell number may lead to an increase in efficacy. We have already seen, I would say, really groundbreaking or paradigm-changing data. I mean in these Hodgkin lymphoma patients who are triple refractory to chemotherapy, PD-1 and Adcetris, what you would expect with any kind of standard of care is a 10%, maybe 15% response rate, and you basically never see complete responses. So 87% overall response rate, 50% complete response rate is already really paradigm-changing. Whether we can top something on this, the data needs to tell. And we have not seen the final data yet. This will be really freshly prepared for ASH to have the most updated data set.

同樣，目前很難預測或推測細胞數量的增加是否會導致療效的增加。我想說，我們已經看到了真正具有突破性或改變範式的數據。我的意思是，對於這些對化療、PD-1 和 Adcetris 具有三重抗藥性的霍奇金淋巴瘤患者，使用任何標準治療方法所期望的反應率都是 10%，也許是 15%，而且基本上看不到完全反應。因此，87% 的整體回應率和 50% 的完全回應率已經真正改變了範式。我們是否能在這方面取得突破，需要用數據來證明。目前我們還沒有看到最終的數據。這將是真正新鮮的準備，讓 ASH 擁有最新的資料集。

Congrats on the progress.

祝賀你取得進展。

Yes, thank you very much.

是的，非常感謝。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特（Maury Raycroft），傑富瑞（Jefferies）。

This is Amin on for Maury. Two from us. First, on AFM24, you alluded to seeking a potential partnership for '24. Where do you currently stand in terms of partnership discussions? And what type of partnership do you have in mind? And are you thinking about full transfer of the drug or co-development? And I have a follow-up.

這是阿明 (Amin) 代替莫里 (Maury) 上場。我們有兩個。首先，在 AFM24 上，您提到尋求 '24 的潛在合作夥伴關係。就合作討論而言，您目前的立場是什麼？您考慮的合作類型是什麼？您是否考慮全面轉讓該藥物或共同開發？我還有一個後續問題。

Yes. Thanks for the question. So I mean, I think as I responded to the initial question from Li, I believe, like we are evaluating all kind of strategic options. So I mean, I think we're evaluating multiple opportunities that could bring in potential nondilutive capital to the company. So there's not a specific type of partnership that we have in mind. We're just evaluating kind of strategic options in the context of other options that could be pursued that would extend the cash runway for the company.

是的。謝謝你的提問。所以我的意思是，我想正如我在回答李的最初問題時所說的那樣，我相信我們正在評估各種戰略選擇。所以我的意思是，我認為我們正在評估可能為公司帶來潛在非稀釋性資本的多種機會。所以，我們心中還沒有考慮到某種特定類型的合作。我們只是在可以採取的其他選擇的背景下評估這種策略選擇，以延長公司的現金流。

Great. And as a follow-up on that, just given the current cash, what are your thoughts on future prioritization potentially between AFM13 and AFM28?

偉大的。作為後續問題，考慮到目前的現金，您對 AFM13 和 AFM28 之間未來的優先順序有何看法？

Yes. So I mean, I think at this time, right, we continue to develop all 3 programs, right, in parallel. I mean I think as you look across the clinical data from all 3 programs, it warrants continued development of all 3 of these programs. I mean we're showing compelling and differentiated data across all 3 of these programs that address significant unmet medical needs. So I mean, the prioritization, at least at this time, continues to remain on developing all 3 products in parallel.

是的。所以我的意思是，我認為此時，我們會繼續同時開發所有 3 個程式。我的意思是，我認為當您查看所有 3 個項目的臨床數據時，它值得繼續開發這 3 個項目。我的意思是，我們在這三個項目中展示了令人信服的差異化數據，這些項目解決了重大的未滿足的醫療需求。所以我的意思是，至少目前，優先事項仍然是同時開發所有 3 種產品。

Li Chen, H.C. Wainwright.

李晨，H.C.溫賴特。

This is Li in for RK. My question is centered on AFM28. Any thoughts on accelerating the development of the 28 program since we know that one other NK cell engager has been advanced into Phase II in frontline AML? Is your development strategy for 28 to be in frontline or in later line in combination with NK cells?

這是代替 RK 的李。我的問題集中在 AFM28 上。既然我們知道另一個 NK 細胞抑制劑已進入前線 AML 治療的 II 期，您有沒有想過加速 28 個項目的開發？您對 28 的開發策略是作為前線藥物，還是與 NK 細胞結合作為後線藥物？

Li, thanks for the question. Andreas, do you want to respond to Li's question?

李先生，謝謝你的提問。安德烈亞斯，你想回答李的問題嗎？

Yes. So as we said, I think previously, we do see a good monotherapy signal, again, with a relatively small number of patients. The first step now is to really consolidate this monotherapy signal, both in terms of response rate and duration of responses. Let's say, if you stay with a response rate of 50% and show meaningful duration of responses, which in these refractory patients could be probably 4 months or longer -- 4 to 6 months, given the fact that the overall survival expectancy for these refractory patients often is only 4 months, this would give us an option to go on accelerated approval path.

是的。因此，正如我們之前所說，我認為我們確實看到了良好的單一療法訊號，而且患者數量相對較少。現在的第一步是真正鞏固這種單一療法訊號，包括反應率和反應持續時間。假設，如果您保持 50% 的回應率並顯示出有意義的回應持續時間，對於這些難治性患者來說，回應持續時間可能為 4 個月或更長時間 - 4 到 6 個月，考慮到這些難治性患者的整體生存預期通常只有 4 個月，這將為我們提供一個加速審批的選擇。

And this accelerated approval path would be based on a single-arm Phase II study and, by definition, would have to be conducted in later lines, so in patients with unmet medical need and basically no treatment options available. We are aware of the other NK cell engager. This has just started Phase I, probably early Phase II, in combination with a hypomethylating agent and venetoclax. This is a much longer pathway as you, for sure, would need a randomized Phase III study, which can be very expensive, could also be quite costly. So our preferred strategy would be to evaluate, at least initially, an accelerated approval strategy in later lines of AML.

此加速審批路徑將基於單臂 II 期研究，根據定義，必須在後續過程中進行，因此適用於未滿足醫療需求且基本上沒有可用治療選擇的患者。我們了解其他 NK 細胞接合劑。該研究剛開始 I 期，可能已開始 II 期早期階段，將與低甲基化劑和維奈克拉聯合使用。這是一條更長的路徑，因為你肯定需要進行隨機的第三階段研究，這可能非常昂貴，也可能相當昂貴。因此，我們的首選策略是至少在最初階段評估反洗錢後續措施中的加速審批策略。

Maybe a follow-up on that. So previously, you mentioned combining AFM28 with NK cell therapy. Can you comment on the pros and cons of engineered RK and K cells versus CAR NK cells, which would be the preferred candidate if you consider going after this combo strategy?

也許是對此的後續行動。之前您提到將 AFM28 與 NK 細胞療法結合。您能否評論一下工程化 RK 和 K 細胞與 CAR NK 細胞的優缺點？

Yes. So I mean, from all the data that we have seen with Acimtamig in combination with allogeneic NK cells, combining AFM28 with an allogeneic NK cell product is a very logical choice. Again, here, we seem to see even more single-agent activity. Remember, Acimtamig in Hodgkin lymphoma only produces 15% responses. And still, when you add the AlloNK cells, you end up in the 80% to 90% response range. We would expect to see a similar shift, a similar increase in activity if we would add AlloNK cells.

是的。所以我的意思是，從我們看到的 Acimtamig 與同種異體 NK 細胞結合的所有數據來看，將 AFM28 與同種異體 NK 細胞產品相結合是一個非常合乎邏輯的選擇。再次，我們似乎在這裡看到了更多的單一代理活動。請記住，霍奇金淋巴瘤中的 Acimtamig 僅產生 15% 的反應。而且，當您添加 AlloNK 細胞時，最終的反應範圍會達到 80% 到 90%。如果我們添加 AlloNK 細胞，我們預計會看到類似的轉變，類似的活動增加。

And here, we are looking at different options to pursue an NK cell-based program. I would not agree with the statement that CAR NKs are preferred over a combination of an ICE and free or AlloNK product. Engineered CAR NKs usually are much more difficult to produce, often come associated with significantly higher CMC costs. What we have shown with the MD Anderson trial and what we seem to show now with our LuminICE trial is that we can be at least as active as engineered CAR-NK with a combination, which is easier to produce, probably much cheaper to produce, and we can also use the different components independently of each other.

在這裡，我們正在研究推行基於 NK 細胞的計劃的不同選擇。我不同意 CAR NK 優於 ICE 和遊離或 AlloNK 產品的組合的說法。工程化的 CAR NK 通常更難生產，並且往往伴隨更高的 CMC 成本。我們在 MD Anderson 試驗中所展示的以及我們現在透過 LuminICE 試驗似乎展示的是，我們至少可以與工程化的 CAR-NK 一樣活躍，但組合更容易生產，生產成本可能更低，而且我們還可以獨立使用不同的組件。

What we have shown in MD Anderson, for example, is that the effect is not only driven by the infused allogeneic NK cell, but that the ability to give free ICE like we do in LuminICE and like we have done in the MD Anderson trial, also can recruit patients' own NK cells. So you have a dual attack with patients' own NK cells and transfused allogeneic NK cells, again, something that you cannot do with a CAR NK. So I would turn the argument rather around and say, if you can go with an ICE and a non-engineered easily and cheaply to produce AlloNK product, that's preferred over a much more complicated CAR NK construct.

例如，我們在 MD Anderson 所展示的是，這種效果不僅是由注射的同種異體 NK 細胞驅動的，而且像我們在 LuminICE 中所做的那樣以及在 MD Anderson 試驗中所做的那樣，提供免費 ICE 的能力也可以招募患者自身的 NK 細胞。因此，您需要使用患者自身的 NK 細胞和輸入的同種異體 NK 細胞進行雙重攻擊，這也是 CAR NK 無法做到的。因此，我想反過來說，如果你可以使用 ICE 和非工程技術輕鬆且廉價地生產 AlloNK 產品，那麼這比更複雜的 CAR NK 結構更可取。

Yale Jen, Laidlaw & Company.

耶魯仁萊德勞公司。

Just trying to follow up with the previous one a little bit on the AFM28. The first one is that should the next cohort also show robust activities? And you mentioned that you will seek for accelerated approval path. How should we think about the potentially overall study size for that? And any colors on that potentially sort of pivotal study for accelerated path? Then I have a follow-up.

只是想在 AFM28 上稍微跟進前一個內容。第一個問題是下一批人是否也應該表現出強勁的活動？您提到您將尋求加速審批途徑。我們應該如何考慮潛在的整體研究規模？對於這種可能對加速路徑產生關鍵作用的研究，您有何看法？然後我有一個後續問題。

Yale, thanks for the question. Andreas, do you want to speak to Yale's question?

耶魯，謝謝你的提問。安德烈亞斯，你想談談耶魯的問題嗎？

Yes, sure. Yes, I mean accelerated approval always will depend, of course, on your effect size. Given what we have seen so far and again, if this signal should hold up, we have some experience in discussions with FDA on our Acimtamig program, where we also talked about accelerated approval. I would say what FDA usually wants to see an accelerated approval trial would be efficacy population somewhere between 80 and probably 100 patients. They do want to see some dose finding studies, which we are already conducting to really be able to judge on the dose effect relationship. And so I think that is a fair estimate of how an accelerated approval trial would have to look like.

是的，當然。是的，我的意思是加速批准當然總是取決於你的效果大小。鑑於我們目前所看到的情況，如果這個訊號能夠成立，我們在與 FDA 就 Acimtamig 計劃進行討論方面有一些經驗，我們也談到了加速審批。我想說，FDA 通常希望看到的加速審批試驗的療效人群是 80 到 100 名患者之間。他們確實希望看到一些劑量探索研究，我們已經在進行這些研究，以便能夠真正判斷劑量效應關係。所以我認為這是對加速審批試驗的合理估計。

Okay. Great. Maybe just one more question here, which is if we compare AFM28 versus 13, what we see at least at this stage is AFM28 seems to have actually very robust results without adding additional NK cells. So was there any fundamental differences between 28 and 13 in terms of the drug itself or design itself, maybe rendered 28 has sort of more very promising outcomes at this moment?

好的。偉大的。這裡可能還剩一個問題，如果我們將 AFM28 與 13 進行比較，至少在現階段我們會看到，AFM28 似乎在沒有添加額外 NK 細胞的情況下實際上具有非常穩健的結果。那麼，就藥物本身或設計本身而言，28 和 13 之間是否存在根本區別，也許目前看來 28 具有更有希望的結果？

Thanks for the follow-up question, Yale. Andreas, maybe you want to answer Yale's follow-up question?

感謝耶魯大學的後續提問。安德烈亞斯，也許你想回答耶魯大學的後續問題？

Yes. That is a very difficult question. What we currently believe is that, honestly, the higher activity signal that we are seeing in AML may not be significantly associated to the molecule. We believe that AFM13 and AFM28, even though they are chemically a little bit different, AFM13 being a smaller molecule with a somewhat shorter half-life, we believe both of them are very potent and very capable to activate the innate immune system and then to target NK cells. I think the main difference and why we see some higher single-agent activity in AFM28 is due to the underlying disease.

是的。這是一個非常難的問題。我們目前認為，說實話，我們在 AML 中看到的更高活性訊號可能與分子沒有顯著關聯。我們相信，儘管 AFM13 和 AFM28 在化學上略有不同，AFM13 是一種較小的分子，半衰期稍短，但我們相信它們都非常有效，能夠激活先天免疫系統，然後靶向 NK 細胞。我認為主要的差異以及我們在 AFM28 中看到更高的單一藥物活性的原因是由於潛在的疾病。

If you look at data from non-targeted NK cells, so without any antibody, just the NK cell, consistently in AML, you have seen, even with non-targeted NK cell, response rates in the 20%, probably even up to the lower 30% range, whereas in lymphomas, if you have a non-targeted NK cell, you rarely see any responses. So what we think is that AML cells can be or seem to be more susceptible to NK cell-mediated killing in general. We also think that AML patients may have still a little higher levels of patients' own or intrinsic NK cells that we can activate with our ICE. We know from Hodgkin lymphoma patients, for example, that they basically have no real functional NK cells, at least when they are in very advanced stages.

如果您查看非靶向 NK 細胞的數據，即沒有任何抗體，只有 NK 細胞，在 AML 中，您會看到，即使使用非靶向 NK 細胞，反應率也在 20% 左右，甚至可能高達 30% 以下，而在淋巴瘤中，如果您有非靶向 NK 細胞，您很少會看到任何反應。因此我們認為，AML 細胞總體上似乎更容易受到 NK 細胞介導的殺滅。我們也認為，AML 患者可能仍具有稍高水平的患者自身或內在 NK 細胞，我們可以透過 ICE 活化這些細胞。例如，我們從霍奇金淋巴瘤患者身上了解到，他們基本上沒有真正具有功能的 NK 細胞，至少在他們處於非常晚期的時候。

So I think it's more a difference in the underlying biology that makes AML specifically sensitive for NK cell-mediated killing. And that's why we believe that both a monotherapy development could be possible for AFM28 and for sure, an AFM28 NK cell-based combination should yield even better results.

因此，我認為更多的是基礎生物學上的差異，使得 AML 對 NK 細胞介導的殺滅特別敏感。這就是為什麼我們相信 AFM28 單一療法的開發是可能的，而基於 AFM28 NK 細胞的組合肯定會產生更好的效果。

Great. That's great insight. Congrats on all the progress so far.

偉大的。這是非常深刻的見解。祝賀迄今為止的所有進展。

(Operator Instructions) Dara Azar, Stifel.

(操作員指示) Dara Azar，Stifel。

Dara Azar here for Brad Canino. On AFM24, based on your experience with this mechanism, how can maturation of or confirmation of final ORR by year-end inform us on the quality of final PFS coming next year? And to clarify here, will we get PFS on all 40 patients in first half of '25? Or will there be some excluded patients? And I have a follow-up after that.

達拉·阿扎爾代替布拉德·卡尼諾。關於 AFM24，根據您對該機制的經驗，年底前最終 ORR 的成熟或確認如何讓我們了解明年最終 PFS 的品質？這裡需要澄清的是，我們是否會在 25 年上半年讓所有 40 名患者都獲得 PFS？或是會有一些病人被排除在外嗎？此後我也會進行後續跟進。

Yes. Dara Azar, thanks for the question. Andreas, do you want to respond to Dara Azar's question?

是的。達拉·阿扎爾，謝謝你的提問。安德烈亞斯，你想回答達拉·阿扎爾的問題嗎？

Yes. So the focus, as we said, on the December data disclosure will be on response rate simply because we think that PFS data are not mature at this point as many patients are still on active treatment. Response rate is one important parameter for decision-making. So it will, I think, confirm our belief that we are able to basically break PD-1 or PD-L1 resistance by the dual combination, which would be reflected in a high response rate or in a high rate of patients with significant tumor volume reduction. And again, the mature PFS data, which will drive the final decision are probably due in first half of 2025.

是的。因此，正如我們所說，12 月數據揭露的重點將放在回應率上，因為我們認為 PFS 數據目前尚不成熟，因為許多患者仍在接受積極治療。回應率是決策的一個重要參數。因此，我認為這將證實我們的信念，即我們能夠透過雙重聯合基本上打破 PD-1 或​​ PD-L1 抗藥性，這將反映在高反應率或高比例的患者腫瘤體積顯著縮小。再次，推動最終決策的成熟 PFS 數據可能將於 2025 年上半年公佈。

Again, PFS in a nonrandomized trial is an interesting endpoint. But as later you can report your PFS data, probably the better the data are. So we just have to wait until these data are really mature. And I'm not sure whether I got there was a second part of the question.

再一次，非隨機試驗中的 PFS 是一個有趣的終點。但隨著您稍後報告 PFS 數據，數據可能會變得更好。所以我們只需要等到這些數據真正成熟。而我不確定我是否理解了這個問題的第二部分。

Yes, 40 will we get PFS from all 40 patients? Or will there be some excluded patients?

是的，40 位患者都能獲得 PFS 嗎？或是會有一些病人被排除在外嗎？

Yes. As all protocols, you have, of course, definitions of what constitutes a patient who is eligible for the protocol. I would expect that we will see PFS data from all 40 patients. We may not see response data from all 40 patients as you usually have 1, 2, 3 patients dropping out just for the feature of missing a second scan, but all these patients would be included into the PFS analysis.

是的。與所有協議一樣，當然，對於符合該協議條件的患者，有一個定義。我希望我們能看到所有 40 名患者的 PFS 數據。我們可能無法看到所有 40 名患者的反應數據，因為通常會有 1、2、3 名患者因錯過第二次掃描而退出，但所有這些患者都將納入 PFS 分析。

Okay. And Shawn, you talked about broadening the scope for BD partnering. What do you think is required at this time in terms of signal generation or approval path clarity from a potential partner?

好的。肖恩，您談到了擴大 BD 合作範圍。您認為此時潛在合作夥伴在訊號產生或批准路徑清晰度方面需要做什麼？

Yes. Which molecule, Dara Azar, because I think it's different for each program?

是的。哪種分子，達拉阿扎爾，因為我認為每個程序都是不同的？

Yes. Initially, that was my question to try to understand what you're prioritizing in your pipeline for potential BD opportunities. Maybe lead with that and let us know, please, on what is the next step as far as what you're trying to generate and present to a potential partner to get the ball rolling?

是的。最初，我問這個問題是為了嘗試了解您在潛在 BD 機會管道中優先考慮什麼。也許可以以此為開端，請讓我們知道，就您試圖產生並向潛在合作夥伴呈現的內容而言，下一步是什麼，以推動事情的發展？

Yes. So I mean, I think as I've shared in response to the partnering questions, I mean, I think we're open to discussing partnerships around any of our innate cell engager programs. So I mean, I think we're open to having discussions on the three clinical-stage assets as well as preclinical programs that we have in the pipeline as well as potential target discovery partnerships as well. So I mean, I think there's a multitude of partnering options that exists across the portfolio.

是的。所以我的意思是，我認為正如我在回答合作問題時所說的那樣，我的意思是，我認為我們願意討論圍繞我們任何先天細胞參與計劃的合作夥伴關係。所以我的意思是，我認為我們願意討論我們正在進行的三個臨床階段資產以及臨床前計畫以及潛在的目標發現夥伴關係。所以我的意思是，我認為整個投資組合中存在著多種合作選擇。

I mean I think I get the impression at least that your question is geared more towards the clinical-stage assets and I mean, I think partners have indicated a variety of kind of different things. I mean I think what we've heard from the vast majority of folks is folks are looking to just see a bit more mature data. And I think as Andreas has highlighted the progress across the clinical pipeline, I think the indications that we've received from potential partners is that we are likely approaching data sets that have kind of the maturity as well as the size in terms of number of patients that they're looking to see to gain confidence and more seriously entertain potential partnerships. So that's where we are at this stage in terms of discussions.

我的意思是，我認為我至少有這樣的印象，你的問題更多是針對臨床階段的資產，我的意思是，我認為合作夥伴已經指出了各種不同的事情。我的意思是，我認為我們從絕大多數人那裡聽到的是，人們只是希望看到更成熟的數據。我認為，正如安德烈亞斯所強調的臨床管線進展一樣，我們從潛在合作夥伴那裡得到的跡像是，我們很可能正在接近具有一定成熟度和規模的數據集，他們希望看到這些數據集具有信心，並更認真地考慮潛在的合作夥伴關係。這就是我們現階段的討論內容。

Thank you. And at this time, there are no additional questions in the queue. We would like to thank everyone for participating in today's conference call. You may all disconnect, and have a good day.

謝謝。目前，隊列中沒有其他問題。我們感謝大家參加今天的電話會議。大家可以斷開連接，享受美好的一天。