Mersana Therapeutics Inc (MRSN) 2024 Q1 法說會逐字稿

Good morning, and welcome to the Mersana Therapeutics first-quarter 2024 conference call and webcast. (Operator Instructions)

早安，歡迎來到 Mersana Therapeutics 2024 年第一季電話會議和網路廣播。（操作員說明）

I would now like to turn the call over to Jason Fredette, Senior Vice President, Investor Relations and Corporate Communications. Please note, this call is being recorded.

我現在想將電話轉給投資者關係和企業傳播部高級副總裁傑森·弗雷戴特 (Jason Fredette)。請注意，此通話正在錄音。

Thank you, operator, and good morning, everyone. Before we begin, please note that this call will contain forward-looking statements within the meaning of Federal Securities laws. These statements may include, but are not limited to, those related to our platforms, product candidates, business strategy, clinical trial execution and data, business development efforts, and cash runway.

謝謝接線員，大家早安。在我們開始之前，請注意，本次電話會議將包含聯邦證券法含義內的前瞻性陳述。這些聲明可能包括但不限於與我們的平台、候選產品、業務策略、臨床試驗執行和數據、業務開發工作和現金跑道相關的聲明。

Each of these forward-looking statements is subject to risks and uncertainties that could cause actual results to differ materially from those projected in such statements. These risks and uncertainties are discussed in our annual report on Form 10-K filed with the Securities and Exchange Commission on February 28, 2024, and in subsequent SEC filings.

這些前瞻性陳述均面臨風險和不確定性，可能導致實際結果與此類陳述中預測的結果有重大差異。這些風險和不確定性在我們於 2024 年 2 月 28 日向美國證券交易委員會提交的 10-K 表格年度報告以及隨後向 SEC 提交的文件中進行了討論。

Our filings are available at sec.gov and on our website, mersana.com. Except as required by law, we assume no obligation to update forward-looking statements publicly even if new information, becomes available in the future.

我們的備案文件可在 sec.gov 和我們的網站 mersana.com 上取得。除法律要求外，即使將來出現新訊息，我們也不承擔公開更新前瞻性聲明的義務。

On today's call, we have Mersana's President and Chief Executive Officer, Dr. Marty Huber; and our Chief Operating Officer and Chief Financial Officer, Brian DeSchuytner.

出席今天的電話會議的有 Mersana 總裁兼執行長 Marty Huber 博士；以及我們的營運長兼財務長 Brian DeSchuytner。

With that, let me turn the call over to Marty, to begin our discussion.

接下來，讓我將電話轉給馬蒂，開始我們的討論。

Thank you, Jason, and good morning, everyone. As most of you know, Mersana is an ADC innovator that's advancing product candidates based on its two proprietary platforms. The first of these is Dolasynthen, our next-generation cytotoxic ADC platform; and the second is Immunosynthen, a novel platform that utilizes a STING-agonist payload.

謝謝傑森，大家早安。正如大多數人所知，Mersana 是 ADC 創新者，正在基於其兩個專有平台推進候選產品。第一個是 Dolasynthen，我們的下一代細胞毒性 ADC 平台；第二個是Immunosynthen，這是一個利用STING激動劑有效負載的新型平台。

Let's begin today's call with a brief discussion of new insights about Dolasynthen that we recently shared at both ESGO and AACR. As many of you know, severe neutropenia, peripheral neuropathy, and ocular toxicity have served as key limitations for today's leading ADC platforms. At those congresses, we presented pre-clinical and clinical data that we believe demonstrates Dolasynthen's ability to significantly reduce these types of off-target, platform-related toxicities, as well as other presumed platform-related adverse events that we saw with our own first-generation ADC platform, Dolaflexin.

在今天的電話會議中，我們首先簡要討論我們最近在 ESGO 和 AACR 上分享的有關 Dolasynthen 的新見解。正如許多人所知，嚴重的中性粒細胞減少症、週邊神經病變和眼毒性已成為當今領先 ADC 平台的主要限制。在這些大會上，我們展示了臨床前和臨床數據，我們相信這些數據表明Dolasynthen 能夠顯著減少這些類型的脫靶、平台相關毒性，以及我們在自己的首次試驗中看到的其他假定的平台相關不良事件新一代 ADC 平台 Dolaflexin。

Ultimately, our goal is to reduce ADC platform toxicities to the greatest extent possible in order to both maximize monotherapy efficacy and open the door to combination approaches with other chemotherapy and ADC standards of care. That's something that simply isn't possible with many of today's approved ADCs.

最終，我們的目標是最大程度地降低 ADC 平台的毒性，以便最大限度地提高單一療法的療效，並為與其他化療和 ADC 標準護理的組合方法打開大門。對於當今許多經批准的 ADC 來說，這是根本不可能實現的。

Now, let's move on to XMT-1660, our lead Dolasynthen ADC that targets B7-H4. We're in the midst of a Phase 1 clinical trial that's enrolling patients with solid tumors, including triple-negative and ER-positive breast cancer, ovarian cancer, and endometrial cancers.

現在，讓我們繼續討論 XMT-1660，這是我們針對 B7-H4 的領先 Dolasynthen ADC。我們正在進行一項一期臨床試驗，招募實體瘤患者，包括三陰性和 ER 陽性乳癌、卵巢癌和子宮內膜癌。

B7-H4 is a member of the B7 family of immune checkpoint markers. The scientific literature suggests that B7-H4 is selectively expressed in tumors with limited healthy tissue expression.

B7-H4 是免疫檢查點標記 B7 家族的成員。科學文獻表明，B7-H4 在健康組織表達有限的腫瘤中選擇性表達。

Additionally, we have not seen any clear signs of on-target toxicities in the clinical data presented by our competitors. We believe B7-H4's selective expression and Dolasynthen's ability to reduce off-target platform toxicity have helped us continue advancing the dose escalation portion of our ongoing trial. We are now beyond the dose levels previously investigated clinically with either Dolasynthen or our first-generation platform, and we still have not established a maximum tolerated dose for 1660.

此外，我們在競爭對手提供的臨床數據中沒有看到任何明顯的標靶毒性跡象。我們相信 B7-H4 的選擇性表現和 Dolasynthen 降低脫靶平台毒性的能力幫助我們繼續推進正在進行的試驗的劑量遞增部分。我們現在超越了先前使用 Dolasynthen 或我們的第一代平台進行臨床研究的劑量水平，並且我們仍然沒有確定 1660 的最大耐受劑量。

Based on pre-clinical models, we have identified exposure thresholds that we believe are key to clinical activity. We also have leveraged our clinical data for 1660 to identify doses and schedules that increase the time above this exposure threshold. Additionally, based on emerging data in the B7-H4 space, we also are progressing our biomarker strategy in preparation for expansion and later stages of development.

根據臨床前模型，我們已經確定了我們認為對臨床活動至關重要的暴露閾值。我們也利用 1660 的臨床數據來確定增加暴露閾值以上時間的劑量和時間表。此外，根據 B7-H4 領域的新數據，我們也正在推進我們的生物標記策略，為擴張和後期開發做好準備。

Given that a maximum tolerated dose has not yet been established and objective responses have been seen in this trial, we are continuing to advance dose escalation and backfill cohorts in parallel to optimize our dose, schedule, and biomarker. We now expect to be in a position to announce our initial clinical data and initiate expansion in the second half of this year. All of this work is aimed at positioning XMT-1660 as a potential best-in-class asset, and we are taking the time needed to accomplish our objective.

鑑於尚未確定最大耐受劑量，並且在本試驗中已看到客觀反應，我們將繼續並行推進劑量遞增和回填隊列，以優化我們的劑量、時間表和生物標記。我們現在預計能夠在今年下半年公佈我們的初步臨床數據並開始擴展。所有這些工作都是為了將 XMT-1660 定位為潛在的一流資產，我們正在花時間實現我們的目標。

Now let's shift to XMT-2056, which is the lead candidate we have developed utilizing Immunosynthen. Our Immunosynthen platform is designed to deliver a one-two punch by activating STING in a target-dependent manner in both tumor cells and in tumor-resident myeloid cells.

現在讓我們轉向XMT-2056，它是我們利用Immunosynthen 開發的主要候選藥物。我們的Immunosynthen 平台旨在透過在腫瘤細胞和腫瘤駐留骨髓細胞中以標靶依賴性方式活化STING，提供一對二的打擊。

XMT-2056 is an ADC targeting a novel epitope of HER2 that's distinct from both pertuzumab and trastuzumab. So in addition to its potential as a monotherapy, we believe there may be a range of intriguing paths to pursue for combination treatments with 2056, including combos with other HER2-targeted agents.

XMT-2056 是一種針對 HER2 新型抗原決定位點的 ADC，該抗原表位不同於帕妥珠單抗和曲妥珠單抗。因此，除了作為單一療法的潛力之外，我們相信 2056 的聯合治療可能還有一系列有趣的途徑可供探索，包括與其他 HER2 標靶藥物的組合。

That said, our near-term goal is to advance the dose escalation portion of our Phase 1 clinical trial of 2056. Multiple clinical sites are now open, and we're actively recruiting patients with a range of HER2-positive tumors, including breast, gastric, colorectal, and non-small cell lung cancer.

也就是說，我們的近期目標是推進 2056 年第 1 期臨床試驗的劑量遞增部分。多個臨床中心現已開放，我們正在積極招募一系列 HER2 陽性腫瘤的患者，包括乳癌、胃癌、大腸直腸癌和非小細胞肺癌。

In addition to these lead programs, we also continue making progress with the collaborations we have in place with Johnson & Johnson focusing on Dolasynthen ADC discovery efforts and with Merck KGaA for Immunosynthen discovery efforts.

除了這些主導項目之外，我們還繼續與強生公司合作，重點關注 Dolasynthen ADC 發現工作，並與 Merck KGaA 進行免疫合成發現工作，繼續取得進展。

With that, let's turn the call over to our Chief Operating and Financial Officer, Brian DeSchuytner, to provide a financial update.

接下來，讓我們將電話轉給我們的營運和財務長 Brian DeSchuytner，以提供最新的財務資訊。

Thank you, Marty. Let's get into the financial highlights for the first quarter of 2024, starting with our balance sheet.

謝謝你，馬蒂。讓我們從資產負債表開始，了解 2024 年第一季的財務亮點。

We ended the first quarter with $183.1 million in cash, cash equivalents, and marketable securities. We continue to expect our available funds to support our operating plan commitments into 2026. Please note that our cash runway guidance does not assume any potential milestone payments from our current collaborations or proceeds that we may realize from future collaborations.

第一季末，我們擁有 1.831 億美元的現金、現金等價物和有價證券。我們繼續期望我們的可用資金能夠支持我們到 2026 年的營運計劃承諾。請注意，我們的現金跑道指南並未假設我們目前合作中的任何潛在里程碑付款或我們可能從未來合作中實現的收益。

Turning to the income statement. Collaboration revenue for the first quarter of 2024 was $9.2 million, compared to $7.8 million for the same period in 2023. The year-over-year change was primarily related to the timing of research and CMC activities for the Johnson & Johnson collaboration agreement.

轉向損益表。2024 年第一季的協作收入為 920 萬美元，而 2023 年同期為 780 萬美元。同比變化主要與強生合作協議的研究和 CMC 活動的時間安排有關。

Research and development expenses for the first quarter of 2024 declined significantly to $18.7 million, compared to $47.3 million for the same period in 2023. For the recent quarter, approximately $2.5 million of this spending was related to non-cash stock-based compensation. The year-over-year decline in R&D expenses was primarily related to reduced costs associated with manufacturing and clinical activities for UpRi and reduced employee compensation following the restructuring we announced in July of 2023.

2024 年第一季的研發費用大幅下降至 1,870 萬美元，而 2023 年同期為 4,730 萬美元。最近一個季度，其中約 250 萬美元的支出與非現金股票薪酬相關。研發費用年減主要與 UpRi 製造和臨床活動相關成本的降低以及我們在 2023 年 7 月宣布的重組後員工薪酬的減少有關。

General and administrative expenses for the first quarter of 2024 declined significantly to $11.6 million, compared to $18.3 million during the same period in 2023. Approximately $2.1 million in non-cash stock-based compensation expenses were included in G&A for the most recent quarter. The year-over-year decline in G&A expenses was primarily related to reduced consulting and professional fees and reduced employee compensation expenses following our restructuring. Please note that this restructuring is now substantially complete with no meaningful costs incurred in Q1.

2024 年第一季的一般及管理費用大幅下降至 1,160 萬美元，而 2023 年同期為 1,830 萬美元。最近一個季度的一般管理費用中包含約 210 萬美元的非現金股票補償費用。一般及行政費用的年減主要與重組後諮詢和專業費用的減少以及員工薪酬費用的減少有關。請注意，此次重組現已基本完成，第一季沒有產生任何有意義的成本。

And finally, Mersana's net loss for the first quarter of 2024 was $19.3 million compared to a net loss of $56.2 million for the same period in 2023. That concludes our business update. Operator, would you please open the call to questions from the audience?

最後，Mersana 2024 年第一季的淨虧損為 1,930 萬美元，而 2023 年同期的淨虧損為 5,620 萬美元。我們的業務更新到此結束。接線生，請開始接受觀眾提問嗎？

We will now begin the question-and-answer session. (Operator Instructions) Tara Bancroft, TD Cowen.

我們現在開始問答環節。（操作員說明）Tara Bancroft，TD Cowen。

Hi. Good morning. Thanks for taking the question. So I was hoping you could reiterate or remind us of your expectations for the 1660 data and what exactly you think the bar is? And has that changed at all over time, especially with now, the data going from midyear to the second half? Thank you.

你好。早安.感謝您提出問題。所以我希望您能重申或提醒我們您對 1660 數據的期望以及您認為的具體指標是多少？隨著時間的推移，這種情況是否發生了變化，尤其是現在，數據從年中到下半年？謝謝。

Thank you, Tara. We're not providing -- excuse me -- any specific details about what will be included in the initial data set. One thing we'd like to remind you that we are in this very competitive environment with a few other B7-H4 ADCs in clinical development.

謝謝你，塔拉。抱歉，我們沒有提供有關初始資料集中將包含哪些內容的任何具體細節。我們想提醒您的一件事是，我們與其他一些處於臨床開發階段的 B7-H4 ADC 處於競爭非常激烈的環境中。

That said, we do anticipate that these data would provide preliminary, but meaningful efficacy data as well as safety, tolerability. In addition, we are looking into our biomarker data as well so that we can clinically characterize the data set. And that would be for the totality of the dose escalation as well as backfill populations.

也就是說，我們確實預期這些數據將提供初步但有意義的功效數據以及安全性、耐受性。此外，我們也正在研究我們的生物標記數據，以便我們可以臨床表徵數據集。這將涉及劑量遞增和回填人群的整體情況。

Okay. Thank you.

好的。謝謝。

(Operator Instructions) Kaveri Pohlman, BTIG.

（操作員說明）Kaveri Pohlman，BTIG。

Right. Good morning. Thanks for taking my questions. Can you just provide any additional color on what -- your decision to move the time line data release to second half? And I would also appreciate if you can tell us of how you're making decision on backfilling cohort. Is that based on the PK/PD profile alone? Are you planning to go -- to do high doses to go there to define MTD dose? And/or you'll be selecting optimal dose based on the safety and PK/PD data alone? Also, will you be defining your optimal dose during the update?

正確的。早安.感謝您回答我的問題。您能否就您將資料發佈時間軸推遲到下半年的決定提供任何額外的資訊？如果您能告訴我們您是如何做出回填隊列的決定的，我也將不勝感激。這是僅基於 PK/PD 設定檔嗎？您是否打算去那裡進行高劑量以確定 MTD 劑量？和/或您將僅根據安全性和 PK/PD 數據選擇最佳劑量？另外，您會在更新期間定義最佳劑量嗎？

Thank you. I think I got all your questions. I'll try to do them in the order, but please remind me if I don't capture one of them.

謝謝。我想我已經回答了你所有的問題。我會嘗試按順序完成它們，但如果我沒有捕獲其中之一，請提醒我。

With regards to the timelines, I think, we -- one of the challenges of when you set out guidance on dose escalation studies is you don't know exactly the timing of how many doses you're going to go. And we still have not established an MTD for 1660.

關於時間表，我認為，當你制定劑量遞增研究指南時，面臨的挑戰之一是你不知道要服用多少劑量的確切時間。我們還沒有建立 1660 的 MTD。

The other thing is which, I think, becoming more apparent for ADC, is we're spending a little more time on optimizing schedule as well as dose. And each of those requires additional cohorts. So I think as we've seen with Project Optimus and these others in oncology recently, we really want to optimize our dose and schedule before we go into expansion.

我認為，對於 ADC 來說，另一件事變得更加明顯，那就是我們花了更多的時間來優化時間表和劑量。每一個都需要額外的隊列。因此，我認為正如我們最近在 Optimus 計畫和腫瘤學領域的其他計畫中所看到的那樣，我們確實希望在進行擴張之前優化我們的劑量和時間表。

With regards to the backfill question, that is based on -- we have the flexibility to enroll specific tumor types in backfill once we've cleared that dose level. So we're not doing it based on any specific PK/PD, I would say, but it's more about making sure we have reasonably sized data sets for some of the tumors of interest.

關於回填問題，這是基於——一旦我們清除了劑量水平，我們就可以靈活地在回填中登記特定的腫瘤類型。所以我想說，我們不是根據任何特定的 PK/PD 來做這件事，而是更多地確保我們擁有一些感興趣的腫瘤的合理大小的數據集。

And as well as an opportunity to make sure we have enough patients to feel confident in the dose. Because while your core design is three plus three, you like to have more patients than that at any given dose level to really get comfortable with the recommended Phase 2 dose.

並且還有機會確保我們有足夠的患者對劑量充滿信心。因為雖然您的核心設計是三加三，但您希望在任何給定劑量水平下有更多的患者來真正適應建議的 2 期劑量。

With regards to your question on the high dose, that's still TBD. I mean, we are going to continue to escalate to explore, but we have not established an MTD. But I think as to whether we will formally establish an MTD will be based on the evolving data.

關於你關於高劑量的問題，這仍然是待定。我的意思是，我們將繼續升級探索，但我們還沒有建立MTD。但我認為我們是否會正式建立MTD將基於不斷變化的數據。

That's helpful. Thank you.

這很有幫助。謝謝。

Jonathan Chang, Leerink Partners.

喬納森·張 (Jonathan Chang)，Leerink 合夥人。

Hey, guys. This is Dylan Drakes on for Jonathan. Thanks for taking our question today. So you previously outlined some tumor types the competitors have seen efficacy in B7-H4. Do you still view those as potential expansion indications? Or do you have any further thoughts around where you plan to initiate expansion cohorts?

大家好。我是迪倫德雷克斯 (Dylan Drakes) 替補喬納森 (Jonathan)。感謝您今天提出我們的問題。您之前概述了競爭對手在 B7-H4 中觀察到的功效的一些腫瘤類型。您仍然認為這些是潛在的擴張跡象嗎？或者您對計劃在哪裡啟動擴展隊列有任何進一步的想法嗎？

And then a second one, if I can. You guys also mentioned previously and again today on the call that the improved safety profile that you guys are seeing with 1660 may enable potential combination therapies. Do you have any additional thoughts on what that could look like or where you look to evaluate that?

如果可以的話，然後是第二個。你們之前和今天在電話會議上也多次提到，你們看到 1660 的安全性得到改善，可能會實現潛在的聯合療法。您對它可能會是什麼樣子或您希望在哪裡進行評估還有什麼其他想法嗎？

Let me start on the tumor type question. At this point in time, we have not shifted the tumor types. We -- the four tumor types of most interest to us because they have the highest level (inaudible) remain triple-negative breast cancer, hormone-receptor positive breast cancer, endometrial, and ovarian cancer. Those are the tumor types we're still focusing on in escalation and in our backfills. And those are the tumor types that we would focus on for expansion.

讓我從腫瘤類型問題開始。目前，我們還沒有改變腫瘤類型。我們最感興趣的四種腫瘤類型，因為它們的水平最高（聽不清楚），仍然是三陰性乳癌、荷爾蒙受體陽性乳癌、子宮內膜癌和卵巢癌。這些是我們在升級和回填中仍在關注的腫瘤類型。這些是我們重點關注的腫瘤類型。

What we haven't provided any further detail on is exactly -- while we're guiding that we're going to initiate expansion in the second half, we are not going into the details of which tumor types exactly with. But the goal will be -- but we will be initiating at least one of those expansion cohorts in the second half.

我們沒有提供任何進一步的細節，雖然我們指導我們將在下半年開始擴張，但我們不會詳細說明到底是哪些腫瘤類型。但我們的目標是——但我們將在下半年至少啟動其中一個擴展隊列。

With regards to your second point about the safety profile, I think we'd like to remind you, and this is what we're very pleased with the Dolasynthen data, was we avoid the neuropathy and neurotoxicity and the ocular tox. And the neuropathy is a particular interest.

關於您關於安全性的第二點，我想我們想提醒您，這是我們對 Dolasynthen 數據非常滿意的一點，我們避免了神經病變、神經毒性和眼毒性。神經病是人們特別感興趣的。

For example, if you’re wanting to combine with a platinum-based chemotherapy, you can't do that if you have an ADC that causes neuropathy. Given the data we've shown to-date with UpRi as well as 1592 for our NaPi2b, we're not seeing evidence of meaningful peripheral neuropathy, which would, in theory, allow us -- or potentially allow us with XMT-1660 replicate that to combine with platinum.

例如，如果您想要與鉑類化療藥物合併使用，但如果您的 ADC 會導致神經病變，則您無法做到這一點。鑑於我們迄今為止使用 UpRi 以及 NaPi2b 的 1592 數據顯示的數據，我們沒有看到有意義的周圍神經病變的證據，這在理論上允許或可能允許我們使用 XMT-1660 複製與鉑金結合。

We're also not seeing profound myelosuppression. So if you think about that, potential combinations in breast cancer with TRODELVY are something that we could consider that would not be possible with a myelosuppressive ADC. So those are just the two couple of thoughts on combinations.

我們也沒有看到嚴重的骨髓抑制。因此，如果您考慮到這一點，我們可以認為，乳癌與 TRODELVY 的潛在組合是骨髓抑制 ADC 不可能實現的。這只是關於組合的兩種想法。

Great. I appreciate that. Thanks so much.

偉大的。我很感激。非常感謝。

(Operator Instructions) Brian Cheng, JPMorgan.

（操作員指令）Brian Cheng，摩根大通。

Hey, guys. Thanks for taking our questions this morning. Can you elaborate on your prepared comments related to optimizing efforts behind schedule and biomarker for 1660? How far are you today from identifying the optimal schedule? And are there any specifics on the gating factor that you can provide before moving to those extensions? Thanks for taking our questions.

大家好。感謝您今天早上提出我們的問題。您能否詳細說明您準備好的有關 1660 落後進度和生物標記優化工作的評論？您今天距離確定最佳日程還有多遠？在轉向這些擴充功能之前，您可以提供有關門控因素的任何具體資訊嗎？感謝您回答我們的問題。

What I think is important is we are still in dose escalation, not establish an MTD. One of the reasons we mentioned that we were seeing objective responses -- we did want to make it clear that we are in clinically relevant dose ranges. And so now, it's a matter of getting that dosing schedule right.

我認為重要的是我們仍在劑量遞增中，而不是建立 MTD。我們提到我們看到客觀反應的原因之一是我們確實想明確我們處於臨床相關劑量範圍內。所以現在的問題是如何制定正確的給藥方案。

And I think that is the focus. We do have a better understanding of our PK than we had previously on the evolving data.

我認為這就是重點。與之前對不斷變化的數據的了解相比，我們確實對我們的 PK 有了更好的了解。

And as -- the other thing we highlighted is there's this concept of understanding exposure over time is important. And if you put those two together, how do you get that just right? And that's really our focus over the next cohorts that we're studying to prepare. So that when we come out with the data set, we have a high degree of confidence in not only the dose, but also the schedule.

我們強調的另一件事是，理解隨著時間的推移而暴露的概念很重要。如果你把這兩者放在一起，你怎麼做才能做到恰到好處呢？這確實是我們正在研究準備的下一批人的重點。因此，當我們拿出數據集時，我們不僅對劑量，而且對時間表都有很高的信心。

Michael Schmidt, Guggenheim.

邁克爾·施密特，古根漢。

Hey, guys. Thanks for taking my questions. Just a follow-up on 1660. I guess, is their PK different from what you had expected? And are you surprised that you're not yet seeing MTDs?

大家好。感謝您回答我的問題。只是1660的後續。我想，他們的PK是不是跟你想的不一樣呢？您對尚未看到 MTD 感到驚訝嗎？

I think last time, you said you were in dose level seven. You're obviously far into the active dosing range at this point. But I'm just curious if there's anything unique going on or if this is just part of the regular Project Optimus workflow that has to be done?

我想上次你說你處於七級劑量。此時，您顯然已處於有效劑量範圍內。但我只是好奇是否有什麼獨特的事情發生，或者這只是必須完成的常規 Project Optimus 工作流程的一部分？

I don't think there's so much anything unique. I think one of the things was we had gotten -- with 1592, our NaPi2b Dolasynthen, we have hit dose-limiting ILD at 56 milligrams per meter squared. As we've told -- as we stated last time, we're over that now. So we're at dosing ranges that we haven't been before, and that always -- you always want to be careful when you're into new dose ranges on a platform.

我不認為有什麼特別之處。我認為其中一件事是我們已經得到了——通過 1592，我們的 NaPi2b Dolasynthen，我們已經達到了每平方米 56 毫克的 ILD 劑量限制。正如我們所說，正如我們上次所說，我們現在已經結束了。因此，我們的劑量範圍是以前從未達到過的，而且總是——當你進入平台上的新劑量範圍時，你總是要小心。

And I think the other thing is we've always been confident in our PK, as we've stated before on our previous molecules. We haven't provided data on 1660, but we do see antibody-like half-life for our molecules. And I think when you take that into account, trying to understand what is the optimal schedule to get the right exposure, it's some fine-tuning.

我認為另一件事是我們一直對我們的 PK 充滿信心，正如我們之前在我們之前的分子中所說的那樣。我們尚未提供 1660 的數據，但我們確實看到我們的分子具有類似抗體的半衰期。我認為，當你考慮到這一點，試圖了解獲得正確曝光的最佳時間表時，就需要進行一些微調。

And as your final point on Project Optimus, that is a factor. Because I think historically, we would have been very comfortable just get a dose you're comfortable with, go straight into expansion. And if you have to change the dose, you did.

作為擎天計畫的最後一點，這是一個因素。因為我認為從歷史上看，我們會很舒服，只要得到一個你覺得舒服的劑量，然後直接進入擴張。如果你必須改變劑量，你就這麼做了。

I think in this current environment, we want to have a higher degree of confidence in the recommended Phase 2 dose that we take into expansion. So I think it is just a little bit -- and this has been a -- for a lack of better word, a personal growth for myself is appreciating the more time and energy on dose optimization than historically we did.

我認為在當前的環境下，我們希望對我們在擴展中採用的建議的第二階段劑量有更高的信心。所以我認為這只是一點點——而且這一直是——因為缺乏更好的詞，我自己的個人成長是欣賞比我們歷史上更多的時間和精力在劑量優化上。

Yeah. No, I think that makes sense. And I think other companies have also looked at multiple different schedules before selecting a NaPi2b. Can you comment -- is it every two weeks, I think, in the Phase 1? And what are you looking at as alternatives?

是的。不，我認為這是有道理的。我認為其他公司在選擇 NaPi2b 之前也考慮了多種不同的時間表。您能否評論一下—我想，在第一階段是每兩週一次嗎？您認為什麼是替代方案？

What we previously disclosed is every three weeks or every four weeks, but the protocol has given us the flexibility to look at alternatives, which we are currently doing.

我們之前披露的是每三週或每四周一次，但該協議使我們能夠靈活地尋找替代方案，我們目前正在這樣做。

And then -- yeah, when we look at the Pfizer data that was recently presented at their R&D Day, they obviously saw some very nice enrichment of activity in biomarker-positive patients in triple-negative breast cancer. I think it was almost twice the response rate in positive patients and so.

然後——是的，當我們查看最近在研發日公佈的輝瑞數據時，他們顯然看到了三陰性乳癌生物標記陽性患者的一些非常好的活性豐富。我認為這幾乎是陽性患者反應率的兩倍，等等。

I'm just curious what your approaches might look like for biomarker development. Would you look at a similar -- I think they used an IHC-based assay. Or are there any other things that you could consider to enrich for biomarker expression?

我只是好奇你們的生物標誌物開發方法可能是什麼樣的。你會看一下類似的嗎——我認為他們使用了基於 IHC 的檢測。或者您可以考慮其他任何東西來豐富生物標誌物的表達嗎？

Yeah. Maybe I can take that. That's a great question. We're currently working on our biomarker strategy, and we've not made any final decisions about it at this stage. We're enrolling patients' regard with the biomarker status to ensure we fully understand the relationship between B7-H4 expression and the probability of response.

是的。也許我可以接受。這是一個很好的問題。我們目前正在製定我們的生物標記策略，現階段我們尚未對此做出任何最終決定。我們正在收集患者對生物標記狀態的關注，以確保我們充分了解 B7-H4 表達與緩解機率之間的關係。

So in other words, we're retrospectively running an IHC test to establish B7-H4 expression levels. But we think this will be an important part of the development program to be really nail that.

換句話說，我們正在回顧性地進行 IHC 測試來確定 B7-H4 表達量。但我們認為這將是真正解決這個問題的開發計劃的重要組成部分。

Awesome. Great. Thanks for taking my questions.

驚人的。偉大的。感謝您回答我的問題。

Asthika Goonewardene, Truist. Please go ahead.

Asthika Goonewardene，真理主義者。請繼續。

Hi. Good morning, guys, and thanks for taking my questions. So previously, what Michael just asked about as well about dose level seven or 59 mgs per meter squared, that was -- you guys were on there in Q1 this year.

你好。早上好，夥計們，感謝您提出我的問題。所以之前，邁克爾剛剛問過關於劑量水平 7 或每平方米 59 毫克的問題，那就是——你們今年第一季就在那裡。

So let me be direct and just ask, how many dose levels above that have you reached right now today in patients? And then, Marty, you said that you've seen confirmed responses. Have you seen this in more than one dose cohort?

因此，讓我直接問一下，您今天在患者身上達到了多少劑量水平？然後，馬蒂，你說你已經看到了確認的回應。您是否在多個劑量組中看到過這種情況？

We're not getting into the details of either dose levels or the response data. I think it is responses. We did make sure we emphasized that. But I do think when you start looking at dose and schedule, focusing purely on an exact dose number becomes a little less relevant because what you're looking at is the total dose intensity of the regimen. And there's ways you can dial that, both from not only the actual dose you administer, but the frequency with which you administer it.

我們不會詳細介紹劑量水平或反應數據。我認為這是回應。我們確實強調了這一點。但我確實認為，當您開始考慮劑量和時間表時，純粹關注確切的劑量數字變得不太重要，因為您正在考慮的是治療方案的總劑量強度。您可以透過多種方法來調節這一點，不僅可以根據您服用的實際劑量，還可以根據您服用的頻率。

So I think what's important is we are looking at more dose-intense approaches to the dos and schedule. But we're not getting into the details of exactly what those are. And part of that is this is something that is fairly competitive space, and understanding ADC dose and schedule is a competitive issue.

所以我認為重要的是我們正在尋找更多劑量密集的劑量和時間表方法。但我們並沒有詳細了解這些內容到底是什麼。部分原因是這是一個競爭相當激烈的領域，了解 ADC 劑量和時間表是一個競爭問題。

Got it. Okay. And so should I read that since you've already tried Q3W, Q4W, you might be looking at some of the other more creative approaches, like Q2W or two-on, one-off? Is that how we should be thinking about it, without getting into specifics?

知道了。好的。那麼我是否應該讀一下，既然您已經嘗試過 Q3W、Q4W，您可能會考慮其他一些更具創意的方法，例如 Q2W 或兩開一關？我們應該這樣思考而不考慮具體細節嗎？

Yeah. We're really not getting into more specifics (technical difficulty) Asthika, I'm sorry. So yeah, we're just not going there at this stage.

是的。我們真的沒有討論更多細節（技術難度）Asthika，我很抱歉。所以，是的，我們現階段不會去那裡。

Okay. Great. Thanks, guys. Appreciate the update.

好的。偉大的。多謝你們。感謝更新。

(Operator Instructions) Ashiq Mubarack, Citi.

（操作員指示）Ashiq Mubarack，花旗銀行。

Hi, guys. Thanks for taking my questions. I think you already addressed my first one, which is just to confirm that the biomarker you're looking at is a B7-H4 biomarker based on IHC. I'm assuming that's correct versus maybe something else.

嗨，大家好。感謝您回答我的問題。我想您已經解決了我的第一個問題，這只是為了確認您正在查看的生物標記物是基於 IHC 的 B7-H4 生物標記物。我認為這是正確的，而不是其他的。

Assuming that's correct, I mean, where are you in the development of an assay? Is that something that's been established or is that something you're building from the ground up. And how robust do you think that assay might be? Thanks.

假設這是正確的，我的意思是，您在檢測開發方面處於什麼階段？這是已經建立的東西還是你正在從頭開始建造的東西。您認為該檢測的穩健性如何？謝謝。

We are not getting into the details of our -- specifics of the biomarker. It is IHC. I think we've confirmed that. But what I think we can say is one of the reasons we are taking a little more time in dose-escalation and optimization in addition to the optimizing dose is it does allow us to generate a larger data set of patients in which we can further understand the biomarker to define such as what is the right biomarker, what is the right cut point, et cetera. So these patients that we're using for dose- escalation backfill are helping us understand that as we go into expansion and pivotal studies.

我們不會詳細介紹生物標記物的具體情況。這是免疫組化。我想我們已經證實了這一點。但我認為我們可以說的是，除了優化劑量之外，我們在劑量遞增和優化上花費更多時間的原因之一是，它確實允許我們產生更大的患者數據集，我們可以在其中進一步了解定義生物標誌物，例如什麼是正確的生物標記、什麼是正確的切點等等。因此，當我們進行擴展和關鍵研究時，我們用於劑量遞增回填的這些患者正在幫助我們了解這一點。

Okay. That's very clear. And then one more on the sequence of events in the second half of the year. I think before, the plan was to announce the initiation of the expansion cohorts and then share the data. Is that still your thinking? Or is this all going to be kind of at once now in the second half of the year?

好的。這非常清楚。然後再談談下半年發生的一系列事件。我認為之前的計劃是宣布啟動擴展隊列，然後共享數據。這還是你的想法嗎？或者這一切會在今年下半年同時發生嗎？

Yeah. We haven't predefined that. So really, the guidance that we've shared for both entering expansion and sharing clinical data, we're just going to leave it at second half for the time being.

是的。我們還沒有預先定義這一點。因此，實際上，我們已經分享了有關進入擴展和共享臨床數據的指導，我們暫時將其留在下半年。

Okay. Thanks very much.

好的。非常感謝。

(Operator Instructions) Colleen Kusy, Baird.

（操作員說明）Colleen Kusy，Baird。

Thanks. Good morning, and thanks for taking our questions. Are you able to clarify whether the multiple responses you're seeing are one or multiple tumor types? And then can you just confirm whether the biomarker data will be in the second-half data update?

謝謝。早安，感謝您提出我們的問題。您能否澄清您看到的多重反應是一種還是多種腫瘤類型？那麼能否確認生物標記數據是否會在下半年數據更新中？

Yeah. So Colleen, we're not going to give more specifics than what we've already shared on responses. And in terms of the biomarker, I would say we're not going to commit to that today. It's something that we're looking very closely at. But that decision will be made at a later date.

是的。所以科琳，我們不會提供比我們已經在回覆中分享的更多細節。就生物標誌物而言，我想說我們今天不會做出承諾。這是我們正在密切關注的事情。但該決定將在稍後做出。

Understood. Thank you. And then for the expansion cohorts, would you plan to run multiple dose levels for an expansion? Or would you select just one?

明白了。謝謝。然後，對於擴展隊列，您是否計劃運行多個劑量等級來進行擴展？還是你會只選一個？

At this point in time that's still TBD. The protocol gives us the option of multiple doses. And I think that will really -- I think in a Project Optimus environment, at some point in time, you are going to have to study more than one dose. The exact timing of when you do that is something that is flexible, and we will be considering it. I think -- but we do have the option. Should we feel we need to do that expansion, we can.

目前仍待確定。此方案為我們提供了多次劑量的選擇。我認為這確實會——我認為在 Optimus 專案環境中，在某個時間點，你將不得不研究不只一劑。您執行此操作的確切時間是靈活的，我們將予以考慮。我認為——但我們確實有選擇。如果我們覺得需要擴展，我們可以。

Great. Thanks for taking my questions.

偉大的。感謝您回答我的問題。

Asthika Goonewardene, Truist.

Asthika Goonewardene，真理主義者。

Hey, guys. Thanks for taking my follow-up. Just one quick one. What's the most important next step right now? Is it pushing to a higher dose level or optimizing exposure? I think you kind of alluded to this already, but I just want to confirm. Thank you.

大家好。感謝您接受我的跟進。就快一點吧。現在最重要的下一步是什麼？是提高劑量水平還是優化暴露？我想你已經提到了這一點，但我只是想確認一下。謝謝。

I think it's an element of both. But really, it's -- from our point of view now, as we better understand how our drugs work, it is this focus on exposure and really getting an optimal dose that we're confident in, that when we take it into expansion, we're not going to have to further modify the dose schedule. That's -- ultimately, that's really what's most important.

我認為這是兩者的一個要素。但實際上，從我們現在的角度來看，隨著我們更好地了解我們的藥物如何發揮作用，正是這種對暴露的關注並真正獲得我們有信心的最佳劑量，當我們將其擴展時，我們不必進一步修改劑量計劃。最終，這才是最重要的。

Thanks. That's really clear. Appreciate it.

謝謝。這真的很清楚。欣賞它。

This concludes our question-and-answer session. I would like to turn the conference back over to Dr. Marty Huber, for any closing remarks.

我們的問答環節到此結束。我想將會議轉回給 Marty Huber 博士，讓其發表閉幕詞。

Thank you, operator, and thanks, everyone, for dialing in. We have several investor events that are taking place over the next several weeks, including -- we'll be at Cowen Oncology Summit as well as at the Goldman Sachs Healthcare Conference. We hope to see some of you there. And that concludes the call, operator. Thank you.

謝謝接線員，也謝謝大家撥電話。我們將在接下來的幾週內舉辦幾場投資者活動，包括—我們將參加考恩腫瘤學高峰會以及高盛醫療保健會議。我們希望在那裡見到你們中的一些人。接線員，通話結束。謝謝。

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

會議現已結束。感謝您參加今天的演講。您現在可以斷開連線。