Mersana Therapeutics Inc (MRSN) 2024 Q4 法說會逐字稿

Good morning, and welcome to Mersana Therapeutics' fourth-quarter and year-end 2024 conference call. Currently, all participants are in a listen-only mode. There will be a question-and-answer session at the end of this call.

早安，歡迎參加 Mersana Therapeutics 2024 年第四季和年終電話會議。目前，所有參與者都處於只聽模式。本次通話結束時將有問答環節。

I would now like to turn the conference over to Jason Fredette, Senior Vice President, Investor Relations and Corporate Communications. Please proceed.

現在，我想將會議交給投資者關係和企業傳播高級副總裁 Jason Fredette。請繼續。

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 the potential clinical benefits of our product candidates and platforms, our clinical trial progress and designs, dosing and patient management strategies, addressable market opportunities, anticipated milestones and data disclosures, 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所定義的前瞻性陳述。這些聲明可能包括但不限於與我們的產品候選和平台的潛在臨床益處、我們的臨床試驗進度和設計、劑量和患者管理策略、可尋址的市場機會、預期的里程碑和數據披露以及現金流相關的聲明。

Each of these forward-looking statements are 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 quarterly report on Form 10-Q filed with the Securities and Exchange Commission on November 13, 2024, and in subsequent SEC filings. 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.

這些前瞻性陳述均受風險和不確定性的影響，可能導致實際結果與這些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 11 月 13 日向美國證券交易委員會提交的 10-Q 表季度報告以及隨後向美國證券交易委員會提交的文件中進行了討論。我們的文件可在 sec.gov 和我們的網站 mersana.com 上查閱。除法律要求外，即使將來有新的資訊出現，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 Chief Executive Officer, Dr. Marty Huber; and our Chief Operating Officer and Chief Financial Officer, Brian DeSchuytner.

今天的電話會議由 Mersana 的執行長 Marty Huber 博士主持；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 the discussion.

說完這些，讓我把電話轉給 Marty 來開始討論。

Thank you, Jason, and good morning, everyone. Over the past several months, we have accomplished a great deal here at Mersana. Most notably, with our lead dolasynthen ADC, Emi-Le, we reported positive initial clinical data, started the expansion portion of our Phase 1 trial and were granted an additional fast track designation for a growing portion of the breast cancer population that has previously been treated with a topoisomerase-1 inhibitor or topo-1 ADC. At the same time, we advanced Phase 1 dose escalation with XMT-2056, our lead immunosynthen ADC, while also supporting our collaborators.

謝謝你，傑森，大家早安。在過去的幾個月裡，我們在梅爾薩納取得了巨大的成就。最值得注意的是，憑藉我們領先的 dolasynthen ADC Emi-Le，我們報告了積極的初步臨床數據，開始了我們第 1 階段試驗的擴展部分，並獲得了額外的快速通道稱號，用於治療之前已接受過拓撲異構酶-1 抑製劑或拓撲-1 ADC 治療的越來越多的乳腺癌人群。同時，我們利用我們的主要免疫合成 ADC XMT-2056 推進了第 1 階段的劑量遞增，同時也為我們的合作者提供支援。

Let's focus first on Emi-Le, Mersana's ADC targeting B7H4. In January, we reported initial clinical data from 130 patients who were enrolled in dose escalation and backfill cohorts as of December 13, 2024, data cutoff. From a safety and tolerability standpoint, Emi-Le was observed to be highly differentiated within the ADC space. The most common treatment-related adverse events of any grade were transient increases in AST, generally asymptomatic and reversible proteinuria, generally low-grade nausea and low-grade fatigue. Importantly, unlike many other ADCs, we did not see dose limiting neutropenia, neuropathy, ocular toxicity, interstitial lung disease or thrombocytopenia.

讓我們先關注 Emi-Le，Mersana 針對 B7H4 的 ADC。1 月份，我們報告了截至 2024 年 12 月 13 日數據截止日期，參與劑量遞增和補充治療的 130 名患者的初步臨床數據。從安全性和耐受性的角度來看，Emi-Le 在 ADC 領域具有高度差異化。任何程度最常見的治療相關不良事件是 AST 暫時升高、通常無症狀且可逆性的蛋白尿、通常低度噁心和低度疲勞。重要的是，與許多其他 ADC 不同，我們沒有看到劑量限制性中性粒細胞減少症、神經病變、眼毒性、間質性肺病或血小板減少症。

This provides us with the confidence that Emi-Le could have an attractive monotherapy profile. Just as importantly, we believe it also could enable combinations with standards of care like platinum chemotherapy and other ADCs that our competitors would be challenged to pursue.

這讓我們有信心，Emi-Le 可能具有有吸引力的單一療法特性。同樣重要的是，我們相信它還可以實現與鉑類化療和其他 ADC 等標準治療相結合，這是我們的競爭對手難以企及的。

From a clinical activity standpoint, confirmed objective responses were observed in all enrolled tumor types. These included patients with triple negative and hormone-receptor-positive breast cancer, endometrial cancer, ovarian cancer and adenoid cystic carcinoma type 1, otherwise known as ACC-1. At intermediate doses, which range from about 38 to 67 milligrams per meter square or about 1 to 2 milligrams per kilogram, the confirmed objective response rate was 23% across all tumor types, with high B7H4 expression, which we defined as an IHC score of 70% or more.

從臨床活動的角度來看，在所有入選的腫瘤類型中都觀察到了確認的客觀反應。這些患者包括三陰性和荷爾蒙受體陽性乳癌、子宮內膜癌、卵巢癌和第 1 型腺樣囊性癌（也稱為 ACC-1）患者。在中等劑量下，即每平方公尺約 38 至 67 毫克或每公斤約 1 至 2 毫克，所有腫瘤類型的確認客觀緩解率為 23%，B7H4 表達較高，我們將其定義為 IHC 評分為 70% 或更高。

Focusing specifically on the evaluable patients in this dose range with B7H4 high triple-negative breast cancer, the confirmed ORR was also 23%. At the end of 2024, we initiated the expansion portion of our trial in patients with TNBC who have previously been treated with at least one topo and one ADC, a population with a very high unmet need.

特別注意該劑量範圍內可評估的 B7H4 高三陰性乳癌患者，確認的 ORR 也為 23%。2024 年底，我們啟動了試驗的擴展部分，對象為先前至少接受過一種拓樸異構酶和一種 ADC 治療的 TNBC 患者，該族群的未滿足需求非常高。

We believe we are positioned for success for a few key reasons. The first is the dose we're utilizing. The second is our inclusion criteria. Third is the standard-of-care for these patients today. And the final factor is the competitive environment in which we are operating.

我們相信，我們能夠成功，主要有幾個原因。首先是我們使用的劑量。第二是我們的納入標準。第三是當今對這些病人的照護標準。最後一個因素是我們所處的競爭環境。

Let's begin with the dose. Generally speaking, as you might expect, we have seen that clinical activity tends to increase along with Emi-Le's dose. As I mentioned, the 23% ORR we observed was generated across a range of doses from about 38 to 67 milligrams per meter square. We have brought the top dose from this range, specifically 67.4 milligram per meter square every four weeks, into expansion. As we previously reported, this particular dose was well tolerated. Additionally, each of the four B7H4 high patients who received this dose achieved target lesion reductions, and each also remained on treatment for durations of approximately 16 weeks or more as of the data cut off.

讓我們從劑量開始。總的來說，正如您所料，我們已經看到臨床活動隨著 Emi-Le 的劑量而增加。正如我所提到的，我們觀察到的 23% ORR 是在每平方公尺約 38 至 67 毫克的劑量範圍內產生的。我們已經將此範圍內的最高劑量（具體為每四周每平方米 67.4 毫克）應用於擴展。正如我們之前報導的，這種特定劑量的耐受性良好。此外，接受該劑量的 4 名 B7H4 高患者均達到了目標病變減少，並且截至數據截止時，每名患者均繼續接受治療約 16 週或更長時間。

A second factor that can influence response is prior treatment. This is well established in oncology and specifically in triple negative breast cancer. As a reminder, the 23% ORR that we observed with Emi-Le and TNBC was generated in a population of 13 evaluable patients. 12 of these patients received more than three lines of prior therapy, and all had received at least one topo-1 ADC.

影響反應的第二個因素是先前的治療。這在腫瘤學中，特別是在三陰性乳癌中已經得到充分證實。提醒一下，我們在 Emi-Le 和 TNBC 中觀察到的 23% ORR 是在 13 名可評估患者群體中產生的。其中 12 名患者曾接受過三種以上的治療，且均接受過至少一種 topo-1 ADC 治療。

These data compare favorably to historical benchmarks. For instance, a 23% ORR was also seen with Trodelvy in TNBC patients who received more than three prior lines of therapy in the Phase 3 ASCENT study. But of course, this was in a total naive setting. Trodelvy's ORR increased to nearly 40% and patients received only two or three prior lines of therapy. In expansion, we are limiting enrollment to patients with a maximum of four prior lines while also mandating that at least one prior treatment must have been a topo-1 ADC. It is also important to keep in mind what the standard-of-care is in TNBC today. In ASCENT, the control arm, which was single agent chemo, had an ORR of only about 5%.

這些數據與歷史基準相比更為有利。例如，在第 3 期 ASCENT 研究中，對於接受過三種以上先前治療的 TNBC 患者，Trodelvy 也觀察到了 23% 的 ORR。但當然，這是在一個完全天真的環境。Trodelvy 的 ORR 增加到近 40%，患者僅接受過兩到三種先前的治療。在擴展方面，我們將入組限制為最多接受過四種既往治療方案的患者，同時也規定至少一種既往治療方案必須是拓樸異構酶-1 ADC。牢記當今 TNBC 的護理標準也很重要。在 ASCENT 中，對照組（單一藥物化療）的 ORR 僅為 5% 左右。

And finally, there is the competitive environment. We view recent developments within the B7H4 ADC landscape as favorable for Emi-Le. Most notably, the company that we have viewed as our primary would-be competitor within the breast cancer space, Pfizer, recently announced that it had discontinued the development of its B7H4 ADC candidate. The other B7H4 ADCs that are at a similar stage of clinical development as us all have topo-1 payloads.

最後，還有競爭環境。我們認為 B7H4 ADC 領域的最新發展對 Emi-Le 有利。最值得注意的是，我們視為乳癌領域主要競爭對手的輝瑞最近宣布已停止其 B7H4 ADC 候選藥物的開發。與我們處於類似臨床開發階段的其他 B7H4 ADC 均具有 topo-1 有效載荷。

As a result, unlike Emi-Le, we believe they are subject to topo-1 resistance mechanisms. In fact, some of these companies appear to be excluding patients who have received prior topo-1 therapies from their clinical trials. This positions Emi-Le as the most advanced auristatin ADC in the class, which provides us with a significant opportunity in breast cancer. We are pleased with the level of investigator interest and engagement we are seeing. And while TNBC is our immediate focus, given the clinical activity we have seen across all tumor types, we are excited by Emi-Le's potential in other indications as well.

因此，與 Emi-Le 不同，我們認為它們受到 topo-1 抗性機制的影響。事實上，其中一些公司似乎將先前接受過 topo-1 療法的患者排除在臨床試驗之外。這使得 Emi-Le 成為同類產品中最先進的奧瑞他汀 ADC，為我們在乳癌治療領域提供了重要機會。我們對研究人員的興趣和參與程度感到高興。雖然 TNBC 是我們目前的關注重點，但鑑於我們在所有腫瘤類型中看到的臨床活動，我們對 Emi-Le 在其他適應症中的潛力也感到興奮。

And so enrollment continues at our initial expansion dose of 67.4 milligrams per meter square. We're also continuing to investigate doses up to 95 milligrams per meter square in escalation of backfill cohorts delays. We're pleased to report that we officially amended our clinical trial protocol in late January as we seek to mitigate the proteinuria-related dose that we were seeing at high doses. We expect these efforts will help us identify a second dose for our second expansion cohort in post-topo-1 TNBC later this year, and we plan to present additional data from dose escalation and backfill later this year as well.

因此，我們繼續按照每平方米 67.4 毫克的初始擴展劑量進行招募。我們也持續調查高達每平方公尺 95 毫克的劑量，以增加補充隊列的延遲。我們很高興地報告，我們在一月底正式修改了臨床試驗方案，以尋求減輕高劑量時出現的蛋白尿相關劑量。我們預計這些努力將幫助我們在今年稍後為拓撲異構酶 1 治療後 TNBC 中的第二個擴展隊列確定第二劑量，並且我們還計劃在今年稍後提供劑量遞增和補充的更多數據。

Moving on to other areas, we also have advanced the dose escalation portion of our Phase 1 clinical trial of XMT-2056 in recent months. 2056 is our immunosynthen STING agonist ADC targeting a novel epitope of HER2. Later in 2025, we plan to present initial pharmacodynamic data from this clinical trial that helps to characterize this candidate's ability to selectively activate the STING pathway in HER2 expressing tumors. And finally, I would like to note that we continue to make solid progress in our dolasynthen research collaboration with J&J and our immunosynthen research collaboration with Merck KGaA.

談到其他領域，近幾個月來，我們也推進了 XMT-2056 第一階段臨床試驗的劑量遞增部分。 2056 是我們針對 HER2 新抗原決定位點的免疫合成 STING 激動劑 ADC。2025 年下半年，我們計劃展示此臨床試驗的初步藥效學數據，以幫助描述該候選藥物選擇性活化 HER2 表達腫瘤中的 STING 路徑的能力。最後，我想指出的是，我們與強生公司的 dolasynthen 研究合作以及與默克公司的 immunityynthen 研究合作繼續取得紮實進展。

With that, let's turn things over to Brian for some color on our financials.

好了，讓我們把話題轉到 Brian 身上，讓他來為我們講講財務狀況。

Thank you, Marty. Beginning with our balance sheet, we ended 2024 with $134.6 million in cash, cash equivalents and marketable securities. We continue to expect that our capital resources will support our current operating plan commitments into 2026. Please note that our cash runway guidance does not assume any future milestone payments that we may earn from our current collaborations or proceeds that we may realize from future collaborations.

謝謝你，馬蒂。從我們的資產負債表開始，到 2024 年底，我們的現金、現金等價物和有價證券為 1.346 億美元。我們繼續預計，我們的資本資源將支持我們目前的營運計劃承諾直至 2026 年。請注意，我們的現金流指導並不假設我們可能從當前合作中獲得的任何未來里程碑付款或我們可能從未來合作中獲得的收益。

Net cash used in operating activities for the fourth quarter of 2024 was $19.3 million, which is down significantly from $32 million in net cash used in operating activities during the year ago quarter. This decrease primarily reflects our portfolio reprioritization efforts, including the OpEx reductions we implemented in the second half of 2023 as part of our restructuring.

2024 年第四季經營活動所用淨現金為 1,930 萬美元，較去年同期的 3,200 萬美元經營活動所用淨現金大幅下降。這一下降主要反映了我們重新調整投資組合的努力，包括我們在 2023 年下半年作為重組的一部分實施的營運支出削減。

Turning to our income statement, collaboration revenue for the fourth quarter of 2024 was $16.4 million compared to $10.7 million for the same period in 2023. The year-over-year change was primarily related to increased collaboration revenue recognized under our agreements with J&J, Merck KGaA, and GSK.

談到我們的損益表，2024 年第四季的合作收入為 1,640 萬美元，而 2023 年同期為 1,070 萬美元。與去年同期相比的變化主要與我們與強生、默克和葛蘭素史克達成的協議下確認的合作收入增加有關。

Research and development expenses for the fourth quarter of 2024 were $22.3 million compared to $21.5 million for the same period in 2023. For the most recent quarter, approximately $1.7 million of this spending was related to non-cash stock-based compensation. The year-over-year change was primarily related to increased costs associated with manufacturing and clinical development activities for Emi-Le and XMT-2056, which were partially offset by reduced costs related to clinical development activities for a discontinued candidate [operate].

2024 年第四季研發費用為 2,230 萬美元，而 2023 年同期為 2,150 萬美元。最近一個季度，其中約 170 萬美元的支出與非現金股票薪酬有關。與去年同期相比的變化主要與 Emi-Le 和 XMT-2056 的製造和臨床開發活動相關成本的增加有關，但部分被已停產候選藥物 [操作] 的臨床開發活動相關成本的減少所抵消。

General and administrative expenses for the fourth quarter of 2024 declined to $8.9 million compared to $10.1 million during the same period in 2023. Approximately $1.7 million in non-cash stock-based compensation expenses were included in G&A for the most recent quarter. The year-over-year decline was primarily related to reduced employee compensation expenses following our restructuring in 2023 and reduced consulting and professional services fees. And finally, Mersana's net loss for the fourth quarter of 2024 was $14.1 million compared to a net loss of $19.5 million for the same period in 2023.

2024 年第四季的一般及行政費用下降至 890 萬美元，而 2023 年同期為 1,010 萬美元。最近一個季度的一般及行政費用中包括約 170 萬美元的非現金股票薪酬費用。年比下降主要與我們 2023 年重組後員工薪酬支出減少以及諮詢和專業服務費用減少有關。最後，Mersana 2024 年第四季的淨虧損為 1,410 萬美元，而 2023 年同期的淨虧損為 1,950 萬美元。

That concludes our business update. Operator, would you please open the call to questions from the audience?

我們的業務更新到此結束。接線生，請您開始回答觀眾的提問好嗎？

(Operator Instructions) Jonathan Chang, Leerink Partners.

（操作員指示）Jonathan Chang，Leerink Partners。

Hi. This is Yen-Der Li for Jonathan Chang. So the first question I have is that, could you share the latest progress on how you are mitigating the AST [LT] elevation and proteinuria issue related to Emi-Le? And how do you think that might increase your confidence in maintaining the dose intensity at a higher dose level?

你好。我是 Jonathan Chang 的 Yen-Der Li。所以我的第一個問題是，您能否分享有關如何緩解與 Emi-Le 相關的 AST [LT] 升高和蛋白尿問題的最新進展？您認為這會如何增強您在較高劑量水平上維持劑量強度的信心？

Thank you for the question. I'll start with the AST then go into the proteinuria and then get to your last question. So with regards to AST, AST does not result in meaningful amounts of dose delays. And even if a patient does have a delay, it's only about a week. So at this point in time, AST is a transient-reversible phenomena that is not having a meaningful impact on our ability to deliver dose.

謝謝你的提問。我將從 AST 開始，然後討論蛋白尿，最後回答您的最後一個問題。因此，就 AST 而言，AST 不會導致有意義的劑量延遲。即使患者確實出現延誤，也只是大約一週的時間。因此，目前，AST 是一種瞬時可逆現象，對我們輸送劑量的能力沒有重大影響。

With regards to proteinuria, just to reiterate, that is primarily a challenge or leading to dose delays only at the highest dose range. So what we're currently doing is, as we mentioned, we've had an amendment to the protocol which does several things. One, it puts in place mitigation such as ACE inhibitors and ARBs early in a kind of a prophylactic manner to minimize the development of proteinuria.

關於蛋白尿，需要重申的是，這主要是一個挑戰，或僅在最高劑量範圍內導致劑量延遲。因此，正如我們所提到的，我們目前正在做的是對該協議進行修訂，該修訂做了幾件事。第一是及早採取預防性措施，使用血管張力素轉換酶（ACE）抑制劑、血管張力素受體阻斷劑（ARB）等緩解措施，盡量減少蛋白尿的發生。

But importantly, as in the setting of when proteinuria does occur but it is asymptomatic, in that a patient is not having edema, they're not having any serum hypoalbuminemia or serum creatinine changes, for those patients, we're able to maintain dosing by doing a dose reduction as opposed to a dose delay. So we look forward to testing that in the clinic to show that we are able to maintain dose intensity, but the clinical outcome will -- we're doing the experiment now.

但重要的是，當出現蛋白尿但無症狀時，患者沒有水腫，沒有出現任何血清低白蛋白血症或血清肌酸酐變化，對於這些患者，我們可以透過減少劑量而不是延遲劑量來維持劑量。因此，我們期待在臨床上進行測試，以表明我們能夠維持劑量強度，但臨床結果將——我們現在正在進行實驗。

Just a quick follow up on the proteinuria. I think on the [separate call], you did mention that it was related to podocytopathy. And do you think that's caused by B7H4 on target or off-target effect? Just curious about the mechanism.

只是對蛋白尿進行快速追蹤。我認為在 [單獨通話] 中，您確實提到它與足細胞病有關。您認為這是由 B7H4 的標靶效應還是脫靶效應引起的？只是對這個機制感到好奇。

At this point in time, we believe it is off target. Other auristatin payloads that are not for B7H4 have been observed to have albuminuria, the same type of podocyte effect.

目前，我們認為它已經偏離目標。已觀察到其他不針對 B7H4 的奧瑞他汀有效載荷具有白蛋白尿，即相同類型的足細胞效應。

Charles Zhu, LifeSci Capital.

Charles Zhu，生命科學資本。

Regarding your dose expansion criteria of having patients with one to four prior lines of therapy, what's your sense of the distribution of patients that you might be getting that has fewer, call it, one to two as opposed to more, call it, three to four prior lines of therapy?

關於您的劑量擴展標準，即患者之前接受過一至四種療法，您認為您可能接收的患者分佈如何？是接受過較少療法（例如一至兩種療法）的患者，還是接受過較多療法（例如三至四種療法）的患者？

I think it's too early to get that read. I mean, we opened it in the study and we're still gathering data. So I think, it would be premature for me to give guidance on what we think are the lines that are actually going to be in the population. One thing we can clearly say is, for inclusion exclusion criteria, those patients who had previously been on with five, six or seven are excluded from expansion. So at a minimum, it will ensure that patients don't have more than four prior lines. That is part of the protocol.

我認為現在讀這個還為時過早。我的意思是，我們在研究中打開了它並且我們仍在收集數據。因此我認為，現在就我們對人口中實際出現的界限給出指導還為時過早。我們可以明確地說的是，對於納入排除標準，那些先前接受過五、六或七項治療的患者將被排除在擴展之外。因此，至少可以確保患者先前的治療線不超過四條。這是協議的一部分。

Maybe one quick follow up right now. I guess then, I think you went through this a little bit as well, but to what extent will your second go-forward dose, the identification of that, be dependent on your ability to mitigate proteinuria? So you've already selected 67.3 in the intermediate range. And is there a scenario where you go for something, let's call it, in the middle to the higher end of your high dose range if your proteinuria mitigation works very well? Or is there an alternative scenario where you could end up maybe selecting even a separate dose beyond that?

也許現在就可以快速跟進。我想，您也經歷過一點這樣的情況，但是您的第二次繼續用藥劑量以及確定劑量在多大程度上取決於您減輕蛋白尿的能力？因此您已經選擇了中間範圍的 67.3。如果您的蛋白尿緩解效果很好，那麼是否存在一種情況，您可以選擇某種藥物，我們稱之為高劑量範圍的中高端藥物？或者是否存在其他情況，您最終可能會選擇除此之外的單獨劑量？

At this point in time, we are setting doses up to 95 milligrams per meter square. So we are not exploring anything higher than that at this point in time.

目前，我們設定的劑量高達每平方公尺 95 毫克。因此，我們目前還沒有探索比這更高的東西。

(Operator Instructions) Michael Schmidt, Guggenheim.

（操作員指示）邁克爾施密特，古根漢。

This is Paul on for Michael. I wanted to expand a bit on how you're currently thinking about establishing the final biomarker cutoff. Is it reasonable to expect where you land on TPS score to still capture roughly half of the TNBC population? Or could there still be a meaningful swing factor in how you're thinking about B7H4 high?

這是保羅代替麥可。我想稍微擴展一下您目前關於如何確定最終生物標記截止值的思考。是否可以合理地預期，您的 TPS 分數仍能涵蓋約一半的 TNBC 人口？或者，在您對 B7H4 高的看法中是否仍然存在有意義的波動因素？

I think while we continue to explore it, I would be surprised if it's outside of that 40%, plus or minus. 40% to 50% at the upper limit is most likely where we'll end up. To me, it would be very surprising if we end up with more than 50% or substantially less than 40%. (multiple speakers) For proportion of the population, the TPS score could be -- that's TBD, what the actual percent TPS to proportion score number is.

我認為，當我們繼續探索它時，如果它超出 40% 左右，我會感到驚訝。我們最終最有可能達到的上限是 40% 到 50%。對我來說，如果我們最終獲得的結果超過 50% 或遠低於 40%，那將是非常令人驚訝的。（多位發言者）對於人口比例，TPS 分數可能是 - - 實際的 TPS 百分比與比例分數是多少還有待確定。

And then just as a follow up, can you set some expectations for the updated Phase 1 dose escalation and backfill data later this year? Which dose levels are in focus for enrollment? How many additional patients of data can we potentially see? And what's the sort of gating factor for when you'll be ready to provide that update?

然後作為後續問題，您能否對今年稍後更新的第一階段劑量遞增和補充數據設定一些預期？入組時重點關注哪些劑量水平？我們可能還可以看到多少額外患者的數據？當您準備好提供該更新時，有哪些限制因素？

This is Jason. We haven't defined that. What we've said is we plan to present additional escalation and backfill data later on this year. As Marty alluded to, we're looking at doses up to 95 milligrams per meter square, but we haven't defined how much incremental data would be in that readout.

這是傑森。我們還沒有定義這一點。我們說過，我們計劃在今年稍後提供額外的升級和補充數據。正如馬蒂所提到的，我們正在研究每平方公尺高達 95 毫克的劑量，但我們還沒有確定讀數中會有多少增量數據。

Andy Hsieh, William Blair.

安迪謝、威廉布萊爾。

Just one quick one for us. Just looking at the updated deck, I think the only thing that changed is the competitive landscape. Marty, I think you've mentioned a little bit in your prepared remarks about the evolving competitive landscape, but I'm curious if you can kind of dive in deeper about some of the competitors that went to Phase 3 and dropped out. Just hoping to hear a little bit more from you.

對我們來說只有一個快速答案。僅看一下更新後的卡組，我認為唯一改變的是競爭格局。馬蒂，我想你在準備好的發言中已經提到了一些關於不斷變化的競爭格局，但我很好奇你是否可以更深入地談談一些進入第三階段後退出的競爭對手。只是希望能聽到您更多的消息。

I'm going to let Brian give you a more detailed answer on that one.

我會讓布萊恩就這個問題給你一個更詳細的答案。

Yes. As Marty articulated, we believe that Emi-Le is very well positioned in the B7H4 space. As you noted with the departure of one of our competitors, we're the most advanced auristatin B7H4 in development. We're the only company that has shared initial positive efficacy data in our post-topo breast cancer setting.

是的。正如 Marty 所言，我們相信 Emi-Le 在 B7H4 領域中佔有非常有利的地位。正如您注意到的，我們的一個競爭對手已經退出，而我們的奧瑞他汀 B7H4 研發處於最前沿。我們是唯一一家在乳癌術後環境中分享初步積極療效數據的公司。

As you remark, one competitor is moving into pivotal studies in a gynecologic tumor. I think we feel like this is very encouraging because it's an additional validation that you can see meaningful activity on that target, but several topo competitors are very much focused on ovarian and endometrial at this stage.

正如您所說，有一家競爭對手正在進入婦科腫瘤的關鍵研究領域。我認為我們覺得這非常令人鼓舞，因為它是一個額外的驗證，你可以看到該目標的有意義的活動，但目前幾個拓撲競爭對手都非常關注卵巢和子宮內膜。

So we believe, one, in Emi-Le's potential as monotherapy. We also believe that our safety and tolerability profile may afford us an opportunity to combine with things like platinum chemo and other ADCs. And we think long term as a set of development opportunities, some of our competitors might be very challenged to pursue those combinations. And so, I think, as we look at the overall competitive landscape, we view it very favorably.

因此，我們相信，首先，Emi-Le 具有單一療法的潛力。我們也相信，我們的安全性和耐受性特徵可能為我們提供與鉑化療和其他 ADC 等相結合的機會。我們認為，從長遠來看，作為一系列發展機遇，我們的一些競爭對手在追求這些組合時可能會面臨巨大挑戰。因此，我認為，當我們審視整體競爭格局時，我們對其持非常樂觀的看法。

Asthika Goonewardene, Truist.

Asthika Goonewardene，Truist。

Two quick ones, if I may. Could you give us a little bit of clarity on when we could expect some of the expansion cohort data up to 67 milligrams? And then, when you presented the data early this year, we looked at three different intervals, the Q3, the Q4 and then a two on, two off. I'm curious if you're looking at other intervals, maybe like a three on, one off, or any other types of other formats as well just to kind of feather the clutch on the dosing.

如果可以的話，我快速問兩個問題。您能否向我們稍微解釋一下，我們何時可以預期部分擴展隊列數據達到 67 毫克？然後，當您在今年年初展示數據時，我們查看了三個不同的間隔，即第三季度、第四季度，然後是兩個開啟、兩個關閉。我很好奇您是否正在研究其他間隔，也許是三次開啟、一次關閉或任何其他類型的格式，只是為了在劑量上稍微放鬆一點。

It's Marty. I'll answer the second one first. At this point in time, we are not studying any schedules beyond what we previously shared. We are continuing to explore different schedules at this point in time, but they're limited to the three we've already shared. And with regards to expansion, we are not giving any further details on timing of expansion other than to say that we are continuing to enroll patients and investigators remain enthusiastic about the study.

是馬蒂。我先回答第二個問題。目前，我們還沒有研究之前分享過的任何時間表。目前我們正在繼續探索不同的時間表，但僅限於我們已經分享的三個。關於擴展，我們不會提供有關擴展時間的任何進一步細節，只是說我們將繼續招募患者，研究人員對這項研究仍然充滿熱情。

Colleen Kusy, Baird.

科琳·庫西，貝爾德。

This is Nick on for Colleen. So for XMT-2056, just wanted to ask what you have to show on the PD update and if there's a ballpark on how many patients or how much follow up you might have. And if we might see any early efficacy data at that time as well.

我是尼克，代替科琳。因此對於 XMT-2056，我只是想問一下您在 PD 更新中要顯示什麼，以及是否大概知道有多少患者或有多少後續行動。而我們是否也能在那時看到任何早期功效數據。

We're not going into any detail beyond the fact that our primary objective will be to share pharmacodynamic data, showing that we're getting activation of the same pathway in HER2 positive tumors. As far as any other details, we're not sharing at this point in time.

除了我們的主要目標是分享藥效動力學數據，顯示我們在 HER2 陽性腫瘤中活化了相同的途徑之外，我們不會談論任何細節。至於其他細節，我們目前不會分享。

(Operator Instructions) Justin Zelin, BTIG.

（操作員指示）Justin Zelin，BTIG。

This is Jeet for Justin. I believe you had said you're going up to 95 milligrams per meter square, but I do believe there was 115 milligrams dose. Was there any reason why 115 milligrams isn't being explored further? And will we see a meaningful number of patients with proteinuria mitigation as part of this year's update?

這是 Justin 的 Jeet。我相信您說過要達到每平方米 95 毫克，但我相信劑量是 115 毫克。有什麼原因沒有進一步探索 115 毫克嗎？在今年的更新中，我們是否會看到大量蛋白尿患者得到緩解？

Well, first of all, we are not studying 115 milligrams any further. At the 115 milligrams dose, we did observe -- we saw it was reversible, but we did see grade 3 ASC in two of the three patients. And while we could have potentially explored that further, we made the decision that we were not going to because we were getting the exposures we were targeting at 95 milligrams and below. So our focus has been on a cap of the 95 milligrams every four weeks or the variations of that.

嗯，首先，我們不會進一步研究 115 毫克。在 115 毫克劑量下，我們確實觀察到 - 我們看到它是可逆的，但我們確實在三名患者中的兩名中看到了 3 級 ASC。儘管我們本來可以進一步探索這一點，但我們決定不這樣做，因為我們所獲得的曝光量目標為 95 毫克及以下。因此，我們的重點是每四周 95 毫克的上限或其變化。

And on the second question in terms of, again, the additional escalation and backfill data, what we'll show is somewhat time dependent, right, in terms of when we plan to share data, so we're not providing any additional specifics at this stage.

關於第二個問題，再次強調，關於額外的升級和補充數據，我們將展示的內容在某種程度上取決於時間，就我們計劃何時共享數據而言，因此我們現階段不會提供任何其他細節。

And maybe a follow up, with the Pfizer program now discontinued, have you spoken to any KOLs who have been on both the Pfizer study as well as yours? And if so, how do they compare the two agents so far?

也許接下來的問題是，輝瑞計畫現已停止，您是否與參與輝瑞研究和您的研究的關鍵意見領袖 (KOL) 交談過？如果是的話，到目前為止他們如何比較這兩個代理商？

Well, they're not going to give us details of confidential data from Pfizer. I think the main thing has been, at this point in time, we had already heard from the investigators in the KOLs that Pfizer was not going to pursue their B7H4 in TNBC post-topo. That was known even before they discontinued the program overall.

嗯，他們不會向我們提供輝瑞機密資料的詳細資料。我認為最主要的是，此時我們已經從 KOL 的調查人員那裡聽說，輝瑞不會在 TNBC 後繼續使用 B7H4。在他們全面停止該計劃之前就已經知道這一點。

And so we were being approached by investigators to participate in our study because when they basically heard through the grapevine, to be frank, even before our data was disclosed because we meet with these investigators, we have them under CDAs, they looked at our data as a promising opportunity in TNBC post-topo. And to be frank, it was the only game in town for their patients. So that's why we had several of those sites actively decide to join our study. As far as the actual data that Pfizer had in this population, they did not share that with this other than -- once again, other than the state that Pfizer was not pursuing this indication.

因此，研究人員聯繫我們參與研究，因為當他們基本上是透過小道消息聽到這個消息時，坦白說，甚至在我們的數據披露之前，因為我們與這些研究人員會面，我們根據 CDA 與他們會面，他們將我們的數據視為 TNBC 術後的一個有希望的機會。坦白說，對於他們的病人來說，這是唯一的選擇。這就是為什麼我們有幾個網站積極決定加入我們的研究。至於輝瑞公司在該人群中擁有的實際數據，他們沒有與該人群分享，除了——再一次，除了聲明輝瑞公司不會追求這一適應症。

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

我們的問答環節到此結束。我想將會議交還給執行長 Marty Huber 博士，請他致閉幕詞。

Thank you, operator, and thanks, everyone, for dialing in. We'll look forward to seeing many of you at the TD Cowen Healthcare Conference here in Boston tomorrow, as well as at Leerink's Healthcare Conference in Miami next week. That concludes our call, operator. Thank you.

謝謝接線員，也謝謝大家撥入電話。我們期待明天在波士頓舉行的 TD Cowen 醫療保健會議上以及下週在邁阿密舉行的 Leerink 醫療保健會議上見到你們。接線員，我們的通話到此結束。謝謝。

The conference is 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。