Mersana Therapeutics Inc (MRSN) 2025 Q1 法說會逐字稿

Good morning and welcome to the Mersana Therapeutics first-quarter 2025 conference call. (Operator Instructions) I would now like to turn the call over to Mr. Jason Fredette, Senior Vice President, Investor Relations and Corporate Communications. Please proceed, sir.

早安，歡迎參加 Mersana Therapeutics 2025 年第一季電話會議。（操作員指示）現在，我想將電話轉給投資者關係和企業傳播高級副總裁 Jason Fredette 先生。先生，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 in design, addressable market opportunities, anticipated clinical milestones and data presentations 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、我們的臨床試驗設計進展、可尋址的市場機會、預期的臨床里程碑和數據展示以及現金跑道相關的聲明。

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 annual report on Form 10-K filed with the Securities and Exchange Commission on March 3, 2025 and in subsequent SEC filings. Our filings are available at sec.gov and on our website, mersana.com.

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 2025 年 3 月 3 日向美國證券交易委員會提交的 10-K 表年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。

Except as required by law, we assume no obligation to update forward-looking statements publicly even if new information becomes available in the future. 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.

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。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. Let's begin by touching on last week's announcement of Mersana's strategic restructuring and reprioritization plan. This plan includes several cost savings initiatives, among them are the reduction of about 55% of our workforce across functions, the elimination of our internal pipeline development efforts, a reduction of other research activities and a narrowing of our clinical development work with Emi-Le to focus on breast cancer.

謝謝你，傑森，大家早安。首先讓我們來談談上周宣布的 Mersana 策略重組和重新排序計劃。該計劃包括幾項成本節約舉措，其中包括減少各職能部門約 55% 的員工、取消內部管道開發工作、減少其他研究活動以及縮小與 Emi-Le 的臨床開發合作範圍以專注於乳腺癌。

We will continue supporting Phase 1 dose escalation work for XMT-2056 and our ongoing collaborations. Our main objective, however, was to extend our cash runway into mid-2026 to give us the opportunity to generate important objective response rate and durability data for Emi-Le from both of our ongoing Phase 1 dose expansion cohorts.

我們將繼續支持 XMT-2056 的第一階段劑量遞增工作以及我們正在進行的合作。然而，我們的主要目標是將現金流延長至 2026 年中期，以便我們有機會從正在進行的兩個第 1 階段劑量擴展隊列中為 Emi-Le 生成重要的客觀反應率和耐久性數據。

Many of our colleagues learned last week that they will be departing Mersana today, and others will be leaving in the near term. I would like to take a moment to thank them for all they have contributed to our programs and our patient-centric culture.

我們的許多同事上週獲悉，他們將於今天離開梅爾薩納，其他人也將在近期離開。我想花點時間感謝他們為我們的專案和以患者為中心的文化所做的貢獻。

Now let's move on to a very timely topic. Earlier this morning at the ESMO Breast Cancer 2025 Congress in Munich, Dr. Erika Hamilton, who heads up breast cancer research at the Sarah Cannon Research Institute, presented updated clinical data for Emi-Le, our Dolasynthen B7-H4 ADC. The presentation primarily focused on preliminary time-to-event data from patients with triple-negative breast cancer, or TNBC, who are enrolled in our dose escalation and backfill cohorts. Safety and tolerability data in this population remain consistent with those previously reported with no new safety signals.

現在讓我們討論一個非常及時的話題。今天早上早些時候，在慕尼黑舉行的 ESMO 乳癌 2025 大會上，莎拉坎農研究所乳癌研究負責人 Erika Hamilton 博士介紹了我們的 Dolasynthen B7-H4 ADC Emi-Le 的最新臨床數據。該報告主要關注了參與我們劑量遞增和補充隊列的三陰性乳癌 (TNBC) 患者的初步事件發生時間數據。該族群的安全性和耐受性數據與先前報告的數據一致，沒有新的安全訊號。

Now before getting into the clinical activity data, it may be helpful to share a little context upfront. First, it's worth noting that research, as shown B7-H4 expression, is a negative prognostic factor in various cancers, including in TNBC. In other words, clinical outcomes in patients with higher B7-H4 expression are generally worse than those for patients with lower expression. Additionally, it is helpful to know what the performance is for today's standard of care in late-line TNBC, namely single-agent chemotherapy. A key reference for this is ASCENT, Trodelvy's registrational trial in relapsed and refractory TNBC.

現在，在了解臨床活動數據之前，先分享一些背景資訊可能會有所幫助。首先，值得注意的是，研究表明，B7-H4 表達是各種癌症（包括 TNBC）的負面預後因素。換句話說，B7-H4 表達較高的患者的臨床結果通常比較表達較低的患者較差。此外，了解當今晚期 TNBC 的標準治療（即單藥化療）的效果也很有幫助。一個重要的參考是 ASCENT，Trodelvy 在復發和難治性 TNBC 的註冊試驗。

In that trial, patients receiving chemotherapy achieved an objective response rate, or ORR, of only 5%. The median progression-free survival, or PFS was about seven weeks and median overall survival, or OS was about seven months. Those data were from patients who were naive to topo-1 ADCs. Ultimately, we believe that this is the type of time-to-event data that a new agent would need to beat in a potential randomized pivotal trial in post topo-1 TNBC for full approval. And given these low bars, we believe such a randomized trial would not take much longer than a single arm trial.

在該試驗中，接受化療的患者的客觀反應率（ORR）僅為 5%。中位無惡化存活期（PFS）約為七週，中位總存活期（OS）約為七個月。這些數據來自未曾使用過拓樸異構酶-1 ADC 的患者。最終，我們相信，這是一種新藥物需要在拓樸異構酶1治療後三陰性乳癌的潛在隨機關鍵試驗中勝出才能獲得全面批准的時間-事件數據。考慮到這些較低的標準，我們相信這種隨機試驗不會比單組試驗花費更長的時間。

With that, let's briefly recap the clinical activity data presented this morning. The presentation focused on evaluable patients with TNBC, who received intermediate doses of Emi-Le ranging from about 38 milligrams per meter squared up to about 67 milligrams per meter squared. Importantly, more than 80% of these TNBC patients had received a prior topo-1 ADC. Among those patients with B7-H4 low tumors who received four or fewer prior lines of treatment, the ORR was 0%. The median PFS was 6.4 weeks, and the median OS was 5.7 months.

因此，讓我們簡要回顧一下今天上午提供的臨床活動數據。演講的重點是可評估的 TNBC 患者，他們接受了中等劑量的 Emi-Le，劑量範圍從每平方米約 38 毫克到每平方米約 67 毫克。重要的是，超過 80% 的 TNBC 患者曾接受過 topo-1 ADC 治療。對於接受過四線或更少線治療的 B7-H4 低腫瘤患者，ORR 為 0%。中位 PFS 為 6.4 週，中位 OS 為 5.7 個月。

But among those patients with what we have initially characterized as B7-H4 high tumors who received four fewer prior lines of therapy, the ORR was 29%. The median PFS was 16 weeks, and the median OS had not yet been reached as of the data cutoff of March 8.

但是，對於我們最初定義為 B7-H4 高腫瘤且先前接受的治療方案少於四種的患者，ORR 為 29%。中位 PFS 為 16 週，截至 3 月 8 日資料截止日期尚未達到中位 OS。

As a reminder, our current dose expansion cohorts are only enrolling TNBC patients who received four or fewer prior lines of therapy, including at least one prior topo-1 ADC. While some patients with B7-H4 low tumor expression are being enrolled, our primary focus is on the B7-H4 high TNBC population. And so while the sample size from dose escalation of backfill is small, today's presentation sheds further light on why we continue to believe Emi-Le could represent a meaningful improvement over today's standard of care for patients with post topo-1 TNBC.

提醒一下，我們目前的劑量擴展隊列僅招募接受過四種或更少先前療法的 TNBC 患者，包括至少一種先前的 topo-1 ADC。雖然一些 B7-H4 腫瘤表達低的患者正在入組，但我們的主要關注點是 B7-H4 高 TNBC 族群。因此，儘管補充劑量遞增的樣本量很小，但今天的報告進一步闡明了為什麼我們仍然相信 Emi-Le 可以代表對當今拓撲異構酶 1 治療後 TNBC 患者的標準治療的有意義的改善。

The ESMO breast presentation also contained an update on clinical activity observed across all tumor types in dose escalation backfill cohorts as of that data cutoff of March 8. And 8 of 26 evaluable patients with B7-H4 high tumor expression who received intermediate doses of Emi-Le achieved a confirmed response for an ORR of 31%.

ESMO 乳房報告還包含了截至 3 月 8 日數據截止時在劑量遞增補充隊列中觀察到的所有腫瘤類型臨床活動的最新情況。在接受中等劑量 Emi-Le 治療的 26 名可評估 B7-H4 高腫瘤表達患者中，有 8 名獲得了確認反應，ORR 為 31%。

This is an increase from the 23% ORR that was reported based upon our December 2024 data cutoff. Further details are contained in the ESMO breast presentation, which can be accessed on the publication sections of our website at mersana.com. We will be sharing some additional clinical data from dose escalation and backfill cohorts across all tumor types based on that March 8 data cutoff in an oral presentation at ASCO in a couple of weeks.

這比我們根據 2024 年 12 月數據截止報告的 23% ORR 有所增加。更多詳細資訊包含在 ESMO 乳房簡報中，可透過我們網站 mersana.com 的出版物部分查閱。幾週後，我們將在 ASCO 的口頭報告中分享基於 3 月 8 日資料截止日期的所有腫瘤類型劑量遞增和補充隊列的一些額外臨床數據。

So where do we stand with our expansion work with Emi-Le? Well, we're making great progress. Again, in expansion, we are focusing on patients with TNBC who have received one to four prior lines of therapy, including at least one prior topo-1 ADC. Enrollment in our initial expansion cohort that is receiving 67.4 milligrams per meter square dose of Emi-Le every four weeks has advanced rapidly in 2025.

那麼我們與 Emi-Le 擴展工作的進展如何？嗯，我們正在取得很大進展。再次，進一步來說，我們關注的是已經接受過一到四種療法的 TNBC 患者，包括至少一種先前的 topo-1 ADC。我們最初的擴展隊列每四周接受 67.4 毫克/平方公尺劑量的 Emi-Le，2025 年的招募工作進展迅速。

As a reminder, we amended our clinical trial protocol in the first quarter this year with the goal of mitigating proteinuria related dose delays we had seen at higher doses of Emi-Le. These proteinuria management guidelines have now been adopted at our clinical sites.

提醒一下，我們在今年第一季修改了臨床試驗方案，目的是減輕我們在較高劑量的 Emi-Le 中看到的蛋白尿相關的劑量延遲。這些蛋白尿管理指南現已在我們的臨床站點採用。

I'm also happy to share that we recently initiated and have progressed patient enrollment in our second TNBC expansion cohort. These patients are receiving a starting dose of 44.5 milligrams per meter squared of Emi-Le on days 1 and 8 of the first four-week cycle, followed by 80 milligrams per meter square every four weeks. We chose this regiment for a few reasons. First, all four of the evaluable B7-H4 high patients who received the 44.5 milligram per meter squared, day 1, day 8 dose every four weeks in dose escalation of backfill cohorts achieved tumor reductions of at least 30%.

我也很高興地告訴大家，我們最近啟動了第二個 TNBC 擴展隊列的患者招募，並且取得了進展。這些患者在第一個四周週期的第 1 天和第 8 天接受每平方公尺 44.5 毫克的 Emi-Le 起始劑量，之後每四周接受每平方公尺 80 毫克的劑量。我們選擇這個團有幾個原因。首先，在補充治療組的劑量遞增中，所有四名可評估的 B7-H4 高患者每四周接受 44.5 毫克/平方米、第 1 天、第 8 天的劑量，均實現了腫瘤縮小至少 30%。

Second, we believe our recent protocol amendment will enable us to maintain dose intensity and tolerability for our 80-milligram per meter squared Q4 dose. And third, our PK work showed that exposures for this regimen are distinct versus our 67-milligram per meter squared every four-week dose, which we believe may be helpful in the spirit of Project Optimus.

其次，我們相信我們最近的協議修訂將使我們能夠保持每平方公尺 80 毫克 Q4 劑量的劑量強度和耐受性。第三，我們的 PK 工作表明，該方案的暴露量與我們每四周每平方米 67 毫克的劑量不同，我們認為這可能有助於體現 Optimus 項目的精神。

As we continue advancing our work and expansion, we are also witnessing a series of developments that could significantly expand the post topo-1 patient pool. Up until now, in the breast cancer space, topo-1 ADCs have only been approved for relapsed and refractory patients. But in recent months, there have been multiple positive Phase 3 readouts for topos in the frontline setting. Focusing specifically on the TNBC, as we've noted before, global TNBC revenues for Trodelvy in 2025 are projected to exceed $1 billion.

隨著我們不斷推進工作和擴展，我們也見證了一系列可以顯著擴大 topo-1 後患者群體的發展。到目前為止，在乳癌領域，拓樸-1 ADC 僅被批准用於治療復發和難治性患者。但最近幾個月，在前線環境中，拓樸替康的第三階段讀數多次呈現正向態勢。具體關注 TNBC，正如我們之前所指出的，預計 2025 年 Trodelvy 的全球 TNBC 收入將超過 10 億美元。

Just a few weeks ago, positive top line results were shared from ASCENT 4, a clinical trial for the combination of Trodelvy and KEYTRUDA in frontline TNBC. This readout may enable Trodelvy to become the new standard of care for first-line PD-L1 positive TNBC and with results from the Phase 3 ASCENT 3 trial in PD-L1 negative patients, also expected in the weeks ahead, we believe the post-topo-1 TNBC patient population could expand substantially.

就在幾週前，Trodelvy 和 KEYTRUDA 聯合用於治療一線 TNBC 的臨床試驗 ASCENT 4 分享了積極的頂線結果。該讀數可能使 Trodelvy 成為一線 PD-L1 陽性 TNBC 的新護理標準，並且隨著針對 PD-L1 陰性患者的 3 期 ASCENT 3 試驗的結果（預計在未來幾週內公佈），我們相信 topo-1 後 TNBC 患者群體可能會大幅增加。

In summary, we remain excited about Mersana's prospects. We're making great progress with expansion enrollment, and we are looking forward to sharing initial clinical data from expansion in the second half of this year.

總而言之，我們仍然對 Mersana 的前景感到興奮。我們在擴大招生方面取得了很大進展，我們期待在今年下半年分享擴大招生的初步臨床數據。

With that, let's turn the call over to Brian for our financial review.

有了這些，讓我們把電話轉給 Brian 進行財務審查。

Thank you, Marty. Beginning with our balance sheet. We ended the first quarter of 2025 with $102.3 million in cash and cash equivalents. due in part to the restructuring and reprioritization plan we announced last week. We expect that our capital resources will enable us to support our current operating claim commitments into mid-2026.

謝謝你，馬蒂。從我們的資產負債表開始。截至 2025 年第一季度，我們的現金和現金等價物為 1.023 億美元。部分原因是我們上週宣布的重組和重新優先排序計劃。我們預計，我們的資本資源將使我們能夠支持目前的營運索賠承諾，直至 2026 年中期。

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. Net cash used in operating activities for the first quarter of 2025 was $29.3 million.

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。2025年第一季經營活動所用淨現金為2,930萬美元。

Turning to our income statement. Collaboration revenue for the first quarter of 2025 was $2.8 million compared to $9.2 million for the same period in 2024. The year-over-year change was primarily related to reduced revenue recognized under our collaboration and license agreement with J&J and Merck KGaA.

轉向我們的損益表。2025 年第一季的合作收入為 280 萬美元，而 2024 年同期為 920 萬美元。與去年同期相比的變化主要與我們與強生公司和默克公司的合作和許可協議下確認的收入減少有關。

Research and Development expenses for the first quarter of 2025 were $18.3 million compared to $18.7 million for the same period in 2024. For the most recent quarter, approximately $1.4 million of this spending was related to noncash stock-based compensation. The year-over-year change was primarily related to our lower head count and related employee compensation costs partially offset by an increase in costs related to Emi-Le clinical development activities.

2025 年第一季的研發費用為 1,830 萬美元，而 2024 年同期為 1,870 萬美元。最近一個季度，其中約有 140 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我們的員工人數減少和相關員工薪酬成本有關，但與 Emi-Le 臨床開發活動相關的成本增加部分抵消了這一變化。

General and administrative expenses for the first quarter of 2025 declined to $8.9 million compared to $11.6 million during the same period in 2024. Approximately $1.3 million in noncash stock-based compensation expenses were included in G&A for the most recent quarter.

2025 年第一季的一般及行政費用從 2024 年同期的 1,160 萬美元下降至 890 萬美元。最近一個季度的一般及行政費用中包括約 130 萬美元的非現金股票薪酬費用。

The year-over-year decline was primarily related to a reduction in consulting and professional services fees as well as the company's lower head count and related employee compensation costs. And finally, Mersana's net loss for the first quarter of 2025 was $24.1 million compared to a net loss of $19.3 million for the same period in 2024.

年比下降主要與諮詢和專業服務費用的減少以及公司員工人數和相關員工薪酬成本的減少有關。最後，Mersana 2025 年第一季的淨虧損為 2,410 萬美元，而 2024 年同期的淨虧損為 1,930 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。

(Operator Instructions)

（操作員指示）

Tara Bancroft, TD Cowen.

塔拉·班克羅夫特（Tara Bancroft），TD Cowen。

Hi, good morning and thanks for taking the question. So I was hoping you could expand a little bit more even qualitatively on the high dose, especially regarding safety and the updated protocol. I know you mentioned that the PK profiles were pretty distinct, but I'd love to hear more about that. And if an update here will be included in the ASCO update at all. Thanks so much.

大家好，早安，謝謝您回答這個問題。因此，我希望您能夠更詳細地闡述高劑量，特別是關於安全性和更新的方案。我知道您提到過 PK 設定檔非常獨特，但我很想聽到更多有關該設定檔的資訊。並且此處的更新是否會包含在 ASCO 更新中。非常感謝。

Thanks, Tara. Well, just last one first. This is part of the second dose level, the 44.5 is part of expansion. And just to be clear, the data we are sharing at ASCO is based on escalation of backfill only. There is not going to be expansion data at ASCO.

謝謝，塔拉。好吧，先說最後一個。這是第二劑量水平的一部分，44.5 是擴展的一部分。需要明確的是，我們在 ASCO 上分享的數據僅基於回填的升級。ASCO 上不會有擴展數據。

So these data would not be included in that presentation. With regards to the rationale, I think I'm going to work backwards to the PK, one of the things you want to look for when you study a second dose is make sure that from an exposure point of view, it's a discrete dose level, and it's not overlapping.

因此這些數據不會包含在該簡報中。關於基本原理，我想我將逆向推導 PK，研究第二劑時要注意的一件事是確保從暴露的角度來看，它是一個離散的劑量水平，並且不會重疊。

In other words, it needs to be a meaningfuly higher dose because if you think about the Project Optimus project, if you have two doses that are 80% of the patients are overlapping an exposure, it's really not a second dose. So we were looking for a dose that is meaningfully higher than 67.4. So the dose we're putting forward at 44.5-day 1 day followed by 80 is a meaningfully higher exposure than you achieved with 67.

換句話說，它需要一種有意義的更高劑量，因為如果你考慮 Optimus 項目，如果你有兩劑，其中 80％ 的患者重疊暴露，那麼它實際上不是第二劑。因此，我們正在尋找明顯高於 67.4 的劑量。因此，我們提出的劑量是 44.5 天，第 1 天加上第 80 天，比 67 天的暴露量高得多。

And then the final part of, why we believe it's doable is when we evaluated our data, one of the observations we found is the 44.5 day 1, day 8 was the most effective dose in ensuring a tumor reduction at week six. So it clearly had -- I mean I said four out of four patients who were B7-H4 with measurable to it to baseline who got that dose, we fixed. The problem we had with 44.5 was the proteinuria also resulted in patients interrupting treatment. So now we believe with the proteinuria mitigation efforts in place that we will be able to maintain it.

最後，我們相信這是可行的，因為我們評估了數據，我們發現的觀察結果之一是第 1 天、第 8 天的 44.5 劑量是確保第六週腫瘤縮小的最有效劑量。所以很明顯——我的意思是，我說四分之四的 B7-H4 患者在基線時可以測量到該劑量，我們進行了修復。我們在 44.5 時遇到的問題是蛋白尿也導致病人中斷治療。因此，現在我們相信，透過採取緩解蛋白尿的措施，我們將能夠維持這一目標。

Now the question then is, well, why did you go from a day 1, day 8 to then an 80. Well, an 80 is also a meaningfully higher exposure. But fundamentally, you do run into a problem of trying to do a day 1, day 8 and maintaining that every cycle just gets to be challenging, whereas 80 every four weeks gives you an exposure in the ballpark of 44.5 day 1, day 8, But it's much -- when we talk to our investigators, there was a lot of negative feedback about trying to maintain a day 1, day 8 schedule on an ongoing basis. But we do think it's worth it trying to get it in for that -- or didn't get into that first cycle because that really is our best shot at efficacy.

那麼現在的問題是，為什麼你從第 1 天、第 8 天到第 80 天。嗯，80 也意味著更高的曝光率。但從根本上來說，你確實會遇到一個問題，那就是嘗試進行第 1 天、第 8 天的試驗，並且堅持每個週期都會很有挑戰性，而每四周 80 次的試驗可以讓你獲得大約 44.5 次第 1 天、第 8 天的暴露機會，但這太多了——當我們與我們的調查人員交談時，發現很多關於第 8 天的負面計劃。但我們確實認為值得為此嘗試——或者沒有進入第一個週期，因為這確實是我們實現療效的最佳機會。

Okay, great. Thank you so much.

好的，太好了。太感謝了。

Charles Zhu, LifeSci Capital.

Charles Zhu，生命科學資本。

Hey. Good morning, everyone. Thanks for taking the questions. Congrats on the progress and nice to see some of these response rates ticking upwards a bit. I have a question regarding maybe some of the ASCENT 3 and ASCENT 4 studies, either having already read out or about to read out. How might these -- assuming a sense the results are successful, like change standard of care and impact, if at all, your clinical development claims in the post topo setting?

嘿。大家早安。感謝您回答這些問題。恭喜您的進展，很高興看到部分回覆率上升。我有一個關於 ASCENT 3 和 ASCENT 4 的一些研究的問題，要么已經讀過，要么即將讀出。假設結果是成功的，這些會如何改變護理標準和影響（如果有的話），您的臨床開發主張在術後環境中如何？

And really, what I'm getting at here is, would you expect any sort of like different patients based on characteristics or outcomes based on whether or not they get this new standard of care versus getting the prior/current standard of care? Thank you.

實際上，我在這裡要說的是，您是否會根據患者是否接受這種新的護理標準而不是接受以前/當前的護理標準而期望根據患者的特徵或結果對他們產生任何差異？謝謝。

Sure. Maybe I'll take that one. As you know, our expansion cohort is exclusively looking at post topo-1 TNBC. And so I think while we certainly have activity, and we've shown this in the January data disclosure in non-topo pretreated patients in the US and in Western Europe, the penetration of these topo delivering ADCs has been very, very rapid.

當然。也許我會選擇那個。如您所知，我們的擴展隊列專門關注 topo-1 後的 TNBC。因此我認為，雖然我們確實有活動，並且我們已經在 1 月份美國和西歐未接受拓撲替康治療的患者的數據披露中證明了這一點，但這些拓撲替康遞送 ADC 的滲透速度非常非常快。

Each of the recurrent setting, as Marty noted in his remarks. I think what this provides the opportunity for is the earlier those agents are used, the more and more patients fall into this post topo-1 category. And we know that very uniquely we retain activity in that space. In fact, we've been deliberately studying that space because it's one of the highest unmet need in breast cancer.

正如馬蒂在評論中指出的那樣，每一個都是重複出現的場景。我認為這提供了一個機會，越早使用這些藥物，就會有越多的患者屬於這種拓樸異構酶 1 後類別。我們知道，我們以非常獨特的方式保留了該空間的活動。事實上，我們一直在刻意研究這個領域，因為它是乳癌領域未滿足的最大需求之一。

What do you do once you induced resistance phenotype in a patient post topo-1? It's a serious question for many of the physicians. We have been uniquely in the space for B7-H4, recruiting those types of patients to ask that hard question. And so we view this as a very positive development for patients and for the size of the opportunity that we're pursuing.

一旦在患者體內誘導出拓樸異構酶-1 抗性表型，您會怎麼做？對許多醫生來說，這是一個嚴重的問題。我們在 B7-H4 領域獨樹一幟，招募這類患者來提出這個難題。因此，我們認為這對於患者以及我們所追求的機會是一個非常積極的發展。

Got it. Great. Thank you.

知道了。偉大的。謝謝。

Michael Schmidt, Guggenheim.

古根漢美術館的麥可·施密特。

Hey, good morning. Thanks for taking my questions. Yeah, maybe just a couple of follow-ups. Again, nice to see the additional two responses in the -- at the intermediate dose. Could you just comment on what types of patients those were? Were those two TNBC patients or perhaps some of the other histologies? And then yeah, just curious if you could provide some qualitative sort of perhaps comment on the impact of some of the product or amendments that you've implemented to manage some of the proteinuria and prophylaxis.

嘿，早安。感謝您回答我的問題。是的，也許只是一些後續行動。再次，很高興看到中等劑量下另外兩種反應。您能否評論一下這些患者是什麼類型的？這兩名患者是 TNBC 患者還是其他組織學類型的患者？是的，我只是好奇您是否可以提供一些定性的評論，關於您為管理蛋白尿和預防措施而實施的一些產品或修正的影響。

How has that sort of -- what was the experience with that so far? And has that indeed resulted in pre-lowering, proteinuria or delay some of these treatment holes? And then lastly, could you just give us a sense of enrollment at the 67-milligram cohort and how that's been progressing and how substantial this update in the second half later this year will be. Thanks so much.

這種情況如何——到目前為止，這種體驗如何？這是否確實導致了預降低、蛋白尿或延遲了一些治療漏洞？最後，您能否向我們介紹 67 毫克劑量組的招募情況、進展以及今年下半年的更新內容。非常感謝。

I'm going to start work backwards. So on the 67 enrollment, we're not giving further guidance. I think what we -- suffice it to say, we've seen sufficient enrollment that we felt comfortable issuing a new guidance. We kind of -- since we kind of went out of guidance for the year because we'd actually achieved all the stuff we see do.

我要開始倒著做工作了。因此，對於 67 名學生的入學情況，我們不會提供進一步的指導。我認為，我們已經看到足夠的入學人數，因此我們感到可以放心發布新的指導方針。我們有點——因為我們有點超出了今年的指導，因為我們實際上已經實現了我們看到的所有目標。

So we decided that when we looked at our enrollment, we have enough patients that we felt confident we would have a data set. And one of the questions we want to do is make sure we have a data set that had enough durability because that's, as you all recall, from our initial data set that was one of the questions.

因此，我們決定，當我們查看我們的招生情況時，我們有足夠的患者，我們有信心我們會有一個資料集。我們想要解決的問題之一是確保我們擁有一個具有足夠持久性的資料集，因為正如大家所記得的那樣，這是我們最初的資料集中的問題之一。

So I think as far as -- we're not giving actual sample sizes yet. But I think the fact that we've switched from 67 to the second dose should indicate we're doing fine on enrollment. And I think for any of you who happen to get up at 2 AM and listen to Erika's call. And from our people on the ground in Munich have been telling us, the investigator enthusiasm has been hot, and we're seeing that in the enrollment.

所以我認為就目前而言——我們還沒有給出實際的樣本量。但我認為，我們已經從 67 劑轉為第二劑，這一事實表明我們的招生工作進展順利。我想，對於任何在凌晨 2 點起床並聽到 Erika 電話的人來說。我們在慕尼黑的實地人員告訴我們，研究人員的熱情很高，我們在招生中看到了這一點。

So I think this niche of post topo now, we've clearly become if you can -- if you have this trial available for your patients, you're putting your patients on it. So this is -- so that's why I think we're comfortable putting out the new guidance for second half.

所以我認為現在這個 post topo 的利基市場，我們顯然已經變成瞭如果你可以的話 - 如果你為你的病人提供這個試驗，你就讓你的病人參與其中。所以這就是——這就是為什麼我認為我們願意發布下半年的新指導方針。

With regards to the proteinuria, once again, we're not giving a data yet. And I think probably a couple of things that are important to understand about that is the mitigations that we're doing, we do not anticipate them ever taking proteinuria to 0. So we want to be very clear. Our expectation is you're still going to see an AE of proteinuria in these patients. What it is about is managing the other consequences of avoiding the development of serum hypoalbuminemia changes in creatinine.

關於蛋白尿，我們還沒有提供數據。我認為可能需要了解的幾件重要的事情是，我們正在採取的緩解措施並不能將蛋白尿降至 0。所以我們希望說得非常清楚。我們預計您仍然會在這些患者中看到蛋白尿的不良反應。其目的在於管理其他避免血清低白蛋白血症肌酸酐變化的後果。

And I think we're at the point now we're confident enough in our mitigation efforts that we are comfortable opening the expansion at the new dose and regimen. We will at some -- when we share the data on this dose in the second half, then we can get into more details of exactly what that looks like.

我認為，現在我們對我們的緩解措施有足夠的信心，我們可以放心地按照新的劑量和方案開始擴張。當我們在下半年分享有關此劑量的數據時，我們就可以更詳細地了解其具體情況。

And the first question was the 31% ORR --

第一個問題是 31% ORR——

Tumor types. Yeah, those both were ACC 1s. But as far as the more details of that, we -- in our upcoming ASCO presentation, whereas ESMO kind of covered the focused-on TNBC, Erika is going to focus on the other tumor types, including the 31% at the ASCO presentation. and a few more things that we can't disclose yet on that base.

腫瘤類型。是的，它們都是 ACC 1。但就更多細節而言，在我們即將舉行的 ASCO 演示中，ESMO 重點介紹了 TNBC，而 Erika 將重點關注其他腫瘤類型，包括 ASCO 演示中的 31%。還有一些我們目前還不能透露的事情。

Right. Thank you.

正確的。謝謝。

(Operator Instructions)

（操作員指示）

Jonathan Chang, Leerink Partners.

Jonathan Chang，Leerink Partners。

Hi, guys, good morning. Thanks for taking my questions. First question, are there additional dosing regimens that could be further evaluated beyond dose A and B in the expansion? Or have you settled on these two dose cohorts? And second question, can you help set expectations on the upcoming ASCO presentation? What could we learn at ASCO relative to the disclosure today? Thank you.

大家好，早安。感謝您回答我的問題。第一個問題，在擴展中，除了劑量 A 和 B 之外，是否還有其他給藥方案可以進一步評估？還是您已經確定了這兩個劑量組？第二個問題，您能幫忙設定即將舉行的 ASCO 演示的期望嗎？關於今天披露的信息，我們可以在 ASCO 上了解到什麼？謝謝。

First of all, with regards to the doses, these are the two doses that we are taking into expansion. We do not anticipate any others. Obviously, we always were data-driven if we learn something new from the data. But the go-forward plan is that it would be either of these two doses.

首先，關於劑量，這是我們正在擴大的兩劑。我們並不期待任何其他事件。顯然，如果我們從數據中了解到新的東西，我們總是以數據為驅動。但未來的計劃是採用這兩種劑量中的一種。

And in fact, that's one of the reasons we kind of scheduled on this kind of loading that switched to 84 because we believe doing the loading for one cycle and then switching to 80 Q4 is a viable dosing schedule to take forward assuming the data supports it. But we do not -- we've obviously looked at other doses and schedules as part of our backfill. But at this point in time, we don't have any plans to take any of those forward.

事實上，這就是我們安排這種轉換為 84 的負荷的原因之一，因為我們相信進行一個週期的負荷然後轉換為 80 Q4 是一個可行的給藥方案，假設數據支持它。但我們沒有——我們顯然已經考慮過其他劑量和時間表作為補充。但目前，我們還沒有任何計劃推進這些計劃。

And with regards to the ASCO presentation, I think really probably knowing that companies have gotten in trouble for violating embargo, we don't. I mean this is our first oral presentation as a company. And the last thing I would hate to do is be the guy who lost it because I blew it embargo. But the thing I think we can be very clear on to set expectations. This is the backfill and escalation data. There is not going to be expansion data at ASCO.

關於 ASCO 的報告，我認為我們可能真的知道公司會因為違反禁運而陷入麻煩，但我們不知道。我的意思是這是我們作為一家公司第一次口頭陳述。我最不想做的事就是因為違反了禁令而成為失敗者。但我認為我們可以非常清楚地設定期望。這是回填和升級資​​料。ASCO 上不會有擴展數據。

Understood. Thanks for taking my questions.

明白了。感謝您回答我的問題。

Colleen Kusy, Baird.

科琳·庫西，貝爾德。

Hi, good morning. Congrats on all the progress and thanks for taking our questions. Marty, I think you mentioned something about a randomized Phase 3 taking that much longer than a single arm. So could you just provide a little bit more color on what you're thinking on a potential pivotal study? And I have a follow-up, please.

嗨，早安。恭喜您取得的所有進展，並感謝您回答我們的問題。馬蒂，我想你提到過隨機化第 3 階段比單臂研究花費的時間要長得多。那麼，您能否更詳細地介紹一下您對一項潛在的關鍵研究的看法？我還有一個後續問題，請回答。

I mean a lot of people ask us questions of, is your response rate going to be high enough for an accelerated approval. And I think one of the things we're looking -- we think that's actually kind of a relevant question. because fundamentally, if you can do a randomized trial in a similar time frame as a nonrandomized trial, that's always the better way to go.

我的意思是很多人問我們這樣的問題：你們的回覆率是否夠高，能否加速批准？我認為我們正在研究的事情之一——我們認為這實際上是一個相關的問題。因為從根本上來說，如果您可以在與非隨機試驗相似的時間範圍內進行隨機試驗，那麼這始終是更好的方法。

And there's -- I'll give you three reasons to that. One is, from a regulatory point of view, and now you have to think beyond the US on a global basis, a randomized trial, you could file anywhere. A lot of companies have decovery to these accelerated approval strategies with a single log trial, and then you can't go anywhere else and then you're kind of stuck waiting for a randomized trough.

對此，我給三個理由。一是從監管的角度來看，現在你必須從全球角度考慮，超越美國，你可以在任何地方提交隨機試驗。許多公司已經透過單次日誌試驗發現了這些加速審批策略，然後你就無法去其他地方，然後你就只能等待隨機低谷。

The second is you still end up having to do the randomized confirmatory trial. And if that randomized confirmatory trial, it's not well underway or near complete, you can get in trouble of not getting an approval because you haven't progressed your confirmatory trial. And that's a point where the agency has gotten very, very sticky. They really, really want to know that the definition of well underway. It's getting -- they basically want to trial is going to read out before they approve you.

第二，你最終還是必須進行隨機確認試驗。如果隨機確認試驗沒有順利進行或接近完成，您可能會因為尚未進行確認試驗而無法獲得批准。這正是該機構變得非常棘手的一點。他們真的非常想知道「順利進行」的定義。他們基本上是想先進行試驗，然後再批准你。

And then the other area where it comes in, and this is one of the things we were very pleased with sharing at ESMO is things like if you look at diseases like TNBC, post topo especially, where patients are progressing in 6 weeks and dying in six months or less is what's important for physicians is to understand not only the response rate, but stable disease as well.

然後是另一個領域，這是我們非常高興在 ESMO 上分享的事情之一，例如，如果您觀察 TNBC 等疾病，尤其是在拓撲替康治療後，患者在 6 週內病情進展並在 6 個月或更短時間內死亡，那麼對於醫生來說，重要的是不僅要了解反應率，還要了解病情穩定性。

In TNBC post-topo a patient who doesn't progress in 18 weeks is deriving a meaningful benefit from the treatment because we know the natural history of that patient as they progress in six weeks. And then finally, you can actually, in a randomized trial in TNBC by the time you finish enrollment, you'll probably already have enough end points for PFS.

在 TNBC 術後，如果患者在 18 週內病情沒有進展，那麼他將從治療中獲益匪淺，因為我們知道該患者在六週內病情進展的自然病程。最後，實際上，在 TNBC 的隨機試驗中，當您完成註冊時，您可能已經擁有足夠的 PFS 終點。

So you could basically complete your enrollment and almost turn around and look at your PFS endpoint the next day. And then your survival endpoint is literally coming in within months of that. So we think there's an opportunity with a randomized trial to avoid a confirmatory trial and get OS data, even if it's a secondary endpoint rapidly.

因此，您基本上可以完成註冊，第二天就可以轉身查看您的 PFS 端點。然後你的生存終點實際上會在幾個月內到來。因此，我們認為，透過隨機試驗可以避免確認性試驗並快速取得 OS 數據，即使它是次要終點。

And then once you have that data set, we think that makes it all this churn you're seeing at the FDA about are they going to accept randomized trials or do they want placebo-controlled or all that nonsense just goes away if you run a randomized trial because you're walking in with what everybody would agree is the gold standard of trials. Just to be clear, we have not had a formal regulatory advice on this. But on that point, I think I would be shocked if the FDA wouldn't accept a randomized trial with PFS and OS as you're in place.

然後，一旦你有了這個數據集，我們認為這會引起你在 FDA 看到的所有這些混亂，關於他們是否會接受隨機試驗，或者他們是否想要安慰劑對照，或者如果你進行隨機試驗，所有這些廢話都會消失，因為你帶著每個人都同意的試驗黃金標準。需要明確的是，我們尚未就此收到正式的監管建議。但就這一點而言，我認為如果 FDA 不接受您所進行的 PFS 和 OS 隨機試驗，我會感到震驚。

Got it. Okay. Super helpful. And then can you -- in that context, can you just talk about the cutoff for B7-H4 expression and how much additional work needs to be done before you feel like you can totally confirm that?

知道了。好的。超有幫助。然後你能——在這種情況下，你能談談 B7-H4 表達的截止值嗎？以及在你覺得可以完全確認這一點之前還需要做多少額外的工作？

We're doing that work in expansion. There were -- would you switch to a pre-commercial assay; there were a few tweaks in the assay between escalation and backfill and expansion. So in expansion, it is possible that the TPS score comes out to be a slightly different place. But I think what's important to understand is, even if the TPS score shifts a little bit, we still fully anticipate that 40% to 50% of patients are going to be positive. So the actual score may change a little bit, but we would be surprised if the percent of patients who are positive dramatically changed.

我們正在擴大這項工作。有——你會轉換到商業化前檢測嗎？在升級和回填與擴展之間​​的分析中有一些調整。因此，從擴展角度來看，TPS 得分可能會略有不同。但我認為重要的是要明白，即使 TPS 評分略有變化，我們仍然完全預期 40% 到 50% 的患者會呈現陽性。因此實際分數可能會有一點變化，但如果陽性患者的百分比發生顯著變化，我們會感到驚訝。

And that's probably an important point as you think about the competitive landscape because people have different specifications around their research assays, the specification doesn't matter so much sustaining conditions, a standing time the temperature. What you're looking for in B7-H4 is about 40% to 50% of the population. And so regardless of what -- someone describes the conditions of their assay, they're likely identifying the same patients.

當您考慮競爭格局時，這可能是一個重要點，因為人們對其研究分析有不同的規範，規範並不那麼重要，維持條件、靜置時間和溫度。您在 B7-H4 中尋找的是約 40% 到 50% 的人口。因此，無論如何——有人描述了他們的檢測條件，他們很可能識別的是同一個病人。

Got it. That's great. Thanks for taking the questions.

知道了。那太棒了。感謝您回答這些問題。

Andy Hsieh, William Blair.

安迪謝、威廉布萊爾。

Thanks for taking our questions. Two quick ones from us. One is about the post-topo dynamic. I think at the conference, Dr. Tolaney presented almost 200 patients worth of data. showing similar PFS for the intermediates or after an intermediary chemo for topo ADC rechallenge.

感謝您回答我們的問題。我們快速說兩句話。一是關於後地形動態。我認為在會議上，Tolaney 博士展示了近 200 名患者的數據。對於中間體或拓樸異構酶 ADC 再次挑戰的中間化療後顯示出相似的 PFS。

And so that, I guess, from my perspective, statically on resistant phenotype is more longer term, I'm curious about your take on that data. And then secondarily, in the January update for the triple-negative cohort, there were three patients with treatment ongoing. I'm just curious about the status of these three patients for the March update. Thank you.

因此，我想，從我的角度來看，靜態抗性表型是更長期的，我很好奇您對這些數據的看法。其次，在三陰性隊列的 1 月更新中，有三名患者正在接受治療。我只是好奇這三位病人三月的狀況。謝謝。

With regard to your first question, I mean I'm not in Munich. I mean I stay behind because of the restructuring and the earnings. So I cannot -- I want to be careful commenting on my presentation, which I did not see. So I'll have to go back and look at that. We do have people on the ground have to -- we'll find out from them.

關於您的第一個問題，我不在慕尼黑。我的意思是，我留下來是因為重組和收益。所以我不能——我想謹慎地評論我的演講，因為我沒有看到。所以我必須回去看看。我們確實有實地人員——我們會從他們那裡找到答案。

With regards to the details of the ongoing status. I think I would defer that, as I said to the ASCO, we will be giving an update -- the March update for all patients at the ASCO presentation, and I really don't want to front run that.

關於當前狀況的詳細資訊。我想我會推遲這一點，正如我對 ASCO 所說的那樣，我們將在 ASCO 演示中為所有患者提供更新信息 - 三月份的更新信息，我真的不想搶先做到這一點。

Asthika Goonewardene, Truist.

Asthika Goonewardene，Truist。

Hi. This is Karina, for Asthika. Thanks for taking my question. I had a follow-up on the B7-H4 expression. What proportion of patients have been expression rate in your previous presentation, you have 40 out of 130 patients. So should we assume around roughly 30% of the population.

你好。我是卡琳娜 (Karina)，代表阿斯蒂卡 (Asthika)。感謝您回答我的問題。我對 B7-H4 表達進行了追蹤。您之前的報告中有多少比例的患者有表達率，130 名患者中有 40 名。因此，我們應假設約有 30% 的人口。

I think we for TNBC, we're comfortable that a number will be somewhere between 40% and 50% of the population.

我認為對於 TNBC 來說，我們很放心這個數字將在總人口的 40% 到 50% 之間。

Okay. So 40% to 50%. And then also regarding the proteinuria medication strategies for the ACE inhibitor prophylaxis, is that initiated only once the patient exhibits size of proteinuria or at a specific grade threshold?

好的。所以是 40% 到 50%。然後，關於 ACE 抑制劑預防的蛋白尿藥物策略，是否僅在患者出現蛋白尿量或達到特定等級閾值時才開始？

In the new amendment that has now been adopted at most of the sites, you are encouraged to start that prophylactically prior -- I mean, basically at the initiation of treatment unless the patient has a contraindication for the ACE arm.

在目前大多數站點已採用的新修正案中，鼓勵您在治療前就開始預防性治療 - 我的意思是，基本上在治療開始時就開始預防性治療，除非患者對 ACE 組有禁忌症。

Okay. Thank you.

好的。謝謝。

(inaudible) BTIG.

（聽不清楚） BTIG。

Hey, good morning. Thank you for taking the question. Maybe two quick questions from me. With the 67.4 and 44.5 mg doses now moving forward in expansion, what would you ultimately want to see from a target product profile perspective to justify moving 44.5 over the other dose and into pivotal studies? And just in terms of the expansion update later this year, will it be strictly in TNBC patients? Or could we also expect to see, say, ovarian or endometrial patients for that update? Thanks.

嘿，早安。感謝您回答這個問題。我想問兩個簡單問題。隨著 67.4 和 44.5 毫克劑量的不斷擴展，從目標產品概況的角度來看，您最終希望看到什麼，以證明將 44.5 移至其他劑量並進入關鍵研究是合理的？就今年稍後的擴展更新而言，它是否嚴格針對 TNBC 患者？或者我們也可以期待看到卵巢或子宮內膜患者的更新？謝謝。

With regards to your first question, I mean, with -- if the efficacy for the higher dose is not meaningfully better than Q4, 67 Q4 is the dose we would take forward because it's just it is the Prodea is much less of an issue there, and it's just a fairly straightforward and easy regimen to do. The intent of the higher dose intensity upfront is getting patients into response faster, which is important and a very aggressive disease like TNBC, especially these late line post topo patients. What -- with regards to the -- your other question was -- sorry --

關於您的第一個問題，我的意思是，如果較高劑量的療效並不比 Q4 好很多，那麼 67 Q4 就是我們會採取的劑量，因為 Prodea 在那裡的問題不大，而且這是一種相當直接和容易的治療方案。預先採用更高劑量強度的目的是讓患者更快地產生反應，這對於像 TNBC 這樣非常侵襲性的疾病來說非常重要，尤其是這些晚期拓撲替康患者。關於你的另一個問題是——抱歉--

Just in terms of the expansion --

就擴張而言--

And actually, this is -- I'm glad you asked that because this is one of the areas I think we probably did the impact of restructuring, when people are saying, what did we stop doing as part of this, one of the things that we are not doing is we originally had planned to be starting multiple extensions across multiple tumor types. And so one of the reasons we can get by with a smaller organization is it's going to be a very breast cancer-focused expansion program.

實際上，這是——我很高興你問這個問題，因為我認為這是我們可能受到重組影響的領域之一，當人們說，我們作為其中的一部分停止做什麼時，我們沒有做的事情之一就是我們最初計劃在多種腫瘤類型中開始多次擴展。因此，我們能夠透過較小規模的組織實現這一目標的原因之一是，它將是一個以乳癌為重點的擴展計劃。

So the ovarian and endometrial data that we have already in backfill and escalation that will get the ASCO presentation, but there will not be in 2025. new expansion data beyond breast cancer. And that is just an unfortunate consequence of extending cash runway. But we still want to look at those two indications. It's just we had to prioritize at this point in time.

因此，我們已經補充和升級的卵巢和子宮內膜數據將獲得 ASCO 展示，但在 2025 年將不會有乳癌以外的新擴展數據。這只是延長現金流的一個不幸後果。但我們仍然想看看這兩個跡象。只是我們現在必須確定優先事項。

Thank you.

謝謝。

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

我們的問答環節到此結束。我想將會議交還給 Marty Huber 博士，請他做最後發言。先生，請繼續。

Thank you, operator, and thanks, everyone, for dialing in. We look forward to seeing many of you in Chicago and ASCO in a couple of weeks. That concludes our call. Thank you.

謝謝接線員，也謝謝大家撥入電話。我們期待幾週後在芝加哥和 ASCO 見到你們。我們的通話到此結束。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。