Mersana Therapeutics Inc (MRSN) 2023 Q1 法說會逐字稿

Good morning, and welcome to Mersana Therapeutics First Quarter 2023 Conference Call and Webcast. (Operator Instructions) Please note, this event is being recorded.

早上好，歡迎來到 Mersana Therapeutics 2023 年第一季度電話會議和網絡直播。 （操作員說明）請注意，正在記錄此事件。

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

我現在想把電話轉給投資者關係和企業傳播高級副總裁 Jason Fredette。請繼續。

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 include, but are not limited to, those related to the therapeutic potential of our product candidates and the potential of our platforms, business strategy, clinical trial design, execution and data releases regulatory plans and objectives, commercial opportunities, collaborations and potential associated payments, operating expenses and cash runway.

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。這些聲明包括但不限於與我們候選產品的治療潛力和我們平台的潛力、業務戰略、臨床試驗設計、執行和數據發布監管計劃和目標、商業機會、合作和潛在相關的聲明付款、運營費用和現金跑道。

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 February 28, 2023, and in subsequent SEC filings.

這些前瞻性陳述中的每一個都受到風險和不確定性的影響，這些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存在重大差異。這些風險和不確定性在我們於 2023 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美國證券交易委員會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.

我們的文件可在 sec.gov 和我們的網站 mersana.com 上找到。除非法律要求，否則我們不承擔公開更新前瞻性陳述的義務，即使將來有新信息可用也是如此。

So with that, let me turn the call over to Anna Protopapas, our President and Chief Executive Officer.

因此，讓我把電話轉給我們的總裁兼首席執行官 Anna Protopapas。

Thank you, Jason, and hello, everyone. Welcome to our conference call. Joining me today with prepared remarks are Mersana's Chief Medical Officer, Arvin Yang; and Chief Financial Officer, Brian DeSchuytner. We also have other members of management here who will be available to answer your questions. 2023 is shaping up to be a potentially transformational year for Mersana. We are on the verge of a top line data readout for a first-in-class ADC, UpRi, while we also execute other comprehensive clinical development plans for this candidate with the potential to address significant unmet medical needs for patients suffering from ovarian cancer.

謝謝你，傑森，大家好。歡迎參加我們的電話會議。 Mersana 的首席醫療官 Arvin Yang 今天和我一起發表準備好的講話；和首席財務官 Brian DeSchuytner。我們這裡還有其他管理人員可以回答您的問題。 2023 年將成為 Mersana 潛在的轉型年。我們即將獲得一流 ADC UpRi 的頂級數據讀數，同時我們還為該候選人執行其他全面的臨床開發計劃，有可能解決卵巢癌患者未滿足的重大醫療需求。

We are advancing our own pipeline and are also collaborating with several other organizations utilizing our 3 proprietary ADC platforms and [sensing] a large part to the successes we've had on the business development front, we are doing all of this on a strong financial footing.

我們正在推進我們自己的管道，並與其他幾個組織合作，利用我們的 3 個專有 ADC 平台，並且[感覺到]我們在業務發展方面取得的成功在很大程度上，我們在強大的財務基礎上做這一切立足點。

We are pursuing our objectives during a historic period for ADCs, as evidenced by numerous new collaborations, additional approvals, exciting new data presentations and one of the largest biotech acquisitions to date. In platinum resistant ovarian case specifically, mirvetuximab just recently reaffirmed the single-arm accelerated approval pathway. And from a commercial perspective, the early uptake of testing and treatment for this product has demonstrated both the high unmet medical need in platinum resistant ovarian cancer and the willingness of treating physicians to appraise a targeted approach to therapy.

我們正在 ADC 的歷史時期追求我們的目標，許多新的合作、額外的批准、令人興奮的新數據演示和迄今為止最大的生物技術收購之一證明了這一點。特別是在鉑耐藥卵巢病例中，mirvetuximab 最近重申了單臂加速批准途徑。從商業角度來看，該產品的早期檢測和治療表明，鉑耐藥卵巢癌的醫療需求尚未得到滿足，而且治療醫師願意評估有針對性的治療方法。

And so we're in the midst of a very exciting period, thanks to a decade of hard work by the team here at Mersana, the innovative approach that we have taken to ADC platform development and our advanced stage of clinical development with UpRi. We believe we're well positioned to add to the momentum in the field.

因此，我們正處於一個非常激動人心的時期，這要歸功於 Mersana 團隊十年的辛勤工作、我們在 ADC 平台開發中採用的創新方法以及我們與 UpRi 臨床開發的高級階段。我們相信我們已做好準備，可以增加該領域的勢頭。

We are putting a heavy emphasis on our strategy to establish a foundational medicine in ovarian cancer. As we advanced 3 ongoing clinical trials that seek to address areas of high unmet medical need. The first is UPLIFT, a single-arm registration trial in platinum-resistant ovarian cancer. And then [we experienced] a rapid enrollment of approximate 270 patients in this trial and recent product uptick in the platinum-resistant space with unmet medical need from these late-stage patients is very high. UP-NEXT is our Phase III clinical trial of UpRi as a monotherapy maintenance treatment in recurrent platinum-sensitive ovarian cancer.

我們非常重視建立卵巢癌基礎醫學的戰略。我們推進了 3 項正在進行的臨床試驗，旨在解決醫療需求未得到滿足的領域。第一個是 UPLIFT，一項針對鉑耐藥卵巢癌的單臂註冊試驗。然後 [we experienced] 大約 270 名患者快速入組該試驗，最近這些晚期患者的醫療需求未得到滿足的鉑耐藥領域的產品數量增加非常多。 UP-NEXT 是我們的 UpRi III 期臨床試驗，作為複發性鉑敏感卵巢癌的單一療法維持治療。

This trial is designed to serve as a post-approval confirmatory trial of UpRi in the U.S., significantly increase our potential market opportunities by supporting expansion into earlier lines of therapy and support potential approvals outside the U.S. And this UPGRADE-A, our Phase I combination trial of UpRi with carboplatin in platinum-sensitive ovarian cancer. We hope this data will inform our path to earlier lines of treatment.

該試驗旨在作為 UpRi 在美國的批准後確認試驗，通過支持擴展到更早的治療線並支持美國以外的潛在批准，顯著增加我們的潛在市場機會。而這個 UPGRADE-A，我們的 I 期組合UpRi 聯合卡鉑治療鉑敏感卵巢癌的試驗。我們希望這些數據能為我們提供更早治療的途徑。

With top line data from UPLIFT planned for midyear after the upcoming oncology conferences in June and a potential BLA submission around the end of the year, we have begun to prepare for potential commercialization. For instance, we have a platform of small core team of commercial professional with deep ovarian cancer experience. Those are medical affairs function and we're working diligently to ensure we can hit the ground running with NaPi2b testing.

在 6 月即將召開的腫瘤學會議之後，UPLIFT 計劃在年中提供頂線數據，並且可能在年底左右提交 BLA，我們已經開始為潛在的商業化做準備。例如，我們擁有一個由具有深厚卵巢癌經驗的商業專業人士組成的小型核心團隊平台。這些是醫療事務功能，我們正在努力工作以確保我們能夠通過 NaPi2b 測試開始運行。

Beyond UpRi, we continue to make progress in our Phase I trial of XMT-1660, our B7-H4 Dolasynthen product candidate and are working to address the clinical hold the FDA recently placed on our Phase I clinical trial of XMT-2056. To further discuss our clinical plans and progress, I'll turn the call over to Arvin.

除了 UpRi 之外，我們在 XMT-1660（我們的 B7-H4 Dolasynthen 候選產品）的 I 期試驗中繼續取得進展，並正在努力解決 FDA 最近對我們的 XMT-2056 I 期臨床試驗提出的臨床擱置問題。為了進一步討論我們的臨床計劃和進展，我會將電話轉給 Arvin。

Thank you, Anna. Let's begin by discussing UPLIFT. Platinum-resistant ovarian cancer remains an area of significant unmet medical need. Patients at this most advanced stage of disease are heavily pretreated and have a very poor prognosis. For most patients, treatment options are limited to single-agent chemotherapy, which has consistently demonstrated an objective response rate of approximately 12% in previous trials. We're seeking to fill this significant gap in care with UpRi.

謝謝你，安娜。讓我們從討論 UPLIFT 開始。鉑耐藥卵巢癌仍然是一個重大未滿足醫療需求的領域。處於疾病最晚期的患者接受了大量的預處理，預後非常差。對於大多數患者，治療選擇僅限於單藥化療，在之前的試驗中一直顯示出大約 12% 的客觀反應率。我們正在尋求通過 UpRi 填補這一重大的護理空白。

Following the release of data from MIRASOL and based on mirvetuximab's label, it is worth noting several key differences in our trial populations. In UPLIFT, we enrolled an all-comers population and retrospectively are determining NaPi2b positive status as compared to MIRASOL, which preselected for folate receptor alpha-positive patients. We believe that at least a majority of ovarian cancer patients have NaPi2b positive expression. In fact, the large NaPi2b data set that has been presented to date, assessing roughly 400 unique tissue samples suggest that 59% of ovarian cancer patients are NaPi2b positive.

在 MIRASOL 發布數據後，根據 mirvetuximab 的標籤，值得注意的是我們試驗人群的幾個關鍵差異。在 UPLIFT 中，我們招募了一個所有人，並回顧性地確定了與 MIRASOL 相比的 NaPi2b 陽性狀態，MIRASOL 是為葉酸受體 α 陽性患者預選的。我們相信至少大部分卵巢癌患者都有NaPi2b陽性表達。事實上，迄今為止已提供的大型 NaPi2b 數據集評估了大約 400 個獨特的組織樣本，表明 59% 的卵巢癌患者為 NaPi2b 陽性。

In contrast, available data suggests that only a minority of ovarian cancer patients have folate receptor alpha-positive expression. We also enrolled patient in UPLIFT, who have received 1 to 4 prior lines of therapy compared to both SORAYA and MIRASOL, which enrolled patients who had received 1 to 3 prior lines. We believe the differences observed between SORAYA and MIRASOL serve as a reminder how ORR can be influenced by the type and level of patient pretreatment.

相比之下，現有數據表明，只有少數卵巢癌患者俱有葉酸受體 α 陽性表達。我們還在 UPLIFT 中招募了患者，與 SORAYA 和 MIRASOL 相比，他們之前接受過 1 到 4 線治療，後者招募的患者之前接受過 1 到 3 線治療。我們認為，在 SORAYA 和 MIRASOL 之間觀察到的差異提醒了 ORR 如何受到患者預處理類型和水平的影響。

We also enrolled patients with Grade II underlying neuropathy in UPLIFT, while these patients were excluded from both SORAYA and MIRASOL. Our broad inclusion criteria were based largely on the encouraging data from our dose expansion cohort. UPLIFT's primary endpoint is the investigator-assessed objective response rate or ORR in the NaPi2b-positive population. The primary endpoint will aim to exclude the 12% objective response rate for single-agent chemotherapy from the 95% confidence interval.

我們還在 UPLIFT 中招募了具有 II 級潛在神經病變的患​​者，而這些患者被排除在 SORAYA 和 MIRASOL 之外。我們廣泛的納入標準主要基於我們劑量擴展隊列中令人鼓舞的數據。 UPLIFT 的主要終點是研究者評估的客觀反應率或 NaPi2b 陽性人群的 ORR 。主要終點將旨在從 95% 置信區間中排除單藥化療的 12% 客觀反應率。

In addition to ORR, we expect the FDA to evaluate duration of response, or DoR, along with safety and tolerability in the overall context of the UPLIFT data. In addition to UPLIFT, we are continuing to enroll patients in our Phase III UP-NEXT trial. There is a substantial need for new ovarian cancer maintenance treatments as many patients have already exhausted available maintenance options by the time they have recurrent disease.

除了 ORR 之外，我們希望 FDA 評估反應持續時間或 DoR，以及 UPLIFT 數據整體背景下的安全性和耐受性。除了 UPLIFT，我們還在繼續招募患者參加我們的 III 期 UP-NEXT 試驗。由於許多患者在疾病復發時已經用盡了可用的維持治療方案，因此迫切需要新的卵巢癌維持治療。

And with the recent label restrictions related to PARP inhibitors, this need is only getting larger. UP-NEXT is enrolling 350 patients. These patients must be NaPi2b positive and they must have achieved stable disease or better in response to their prior induction chemotherapy. In recognition of the lack of standard of care in the recurrent maintenance, the trial is randomizing patients 2:1 to receive UpRi or placebo. Our primary endpoint for the trial is progression-free survival or PFS by blinded independent control reviews.

隨著最近與 PARP 抑製劑相關的標籤限制，這種需求只會越來越大。 UP-NEXT 正在招募 350 名患者。這些患者必須是 NaPi2b 陽性，並且他們必須已經達到穩定的疾病或更好地響應他們之前的誘導化療。認識到在復發性維持治療中缺乏護理標準，該試驗以 2:1 的比例隨機分配患者接受 UpRi 或安慰劑。我們試驗的主要終點是無進展生存期或 PFS，通過盲法獨立對照審查。

Our third ongoing UpRi trial, UPGRADE-A, is evaluating UpRi in combination with carboplatin. Historically, the combination of carboplatinum and paclitaxel has served as the standard of care in earlier lines of ovarian cancer treatment. However, distinct tolerability challenges, including high rates of severe neutropenia, peripheral neuropathy and alopecia have limited the ability to dose this combination beyond 6 cycles.

我們正在進行的第三項 UpRi 試驗 UPGRADE-A 正在評估 UpRi 與卡鉑的結合。從歷史上看，卡鉑和紫杉醇的組合一直是早期卵巢癌治療的標準療法。然而，明顯的耐受性挑戰，包括嚴重中性粒細胞減少、周圍神經病變和脫髮的高發生率，限制了這種組合給藥超過 6 個週期的能力。

In UPGRADE-A, patients receive UpRi in combination with carboplatinum for up to 6 cycles as an induction treatment and UpRi is then continued as a monthly maintenance monotherapy. We believe the differentiated tolerability profile we observed for UpRi in our monotherapy dose expansion trial without toxicities commonly seen with other ADC platforms, may position it well for used in combinations.

在 UPGRADE-A 中，患者接受 UpRi 聯合卡鉑作為誘導治療長達 6 個週期，然後 UpRi 繼續作為每月維持單一療法。我們相信，我們在單一療法劑量擴展試驗中觀察到的 UpRi 差異化耐受性概況沒有其他 ADC 平台常見的毒性，可能適合聯合使用。

We were pleased to complete dose escalation in UPGRADE-A and move into dose expansion in the first quarter, and we're looking forward to sharing initial interim data in the second half of this year. Before delving into our other clinical stage cytotoxic ADC, XMT-1660, let's touch on XMT-2056 which is our HER2 directed Immunosynthen STING-Agonist ADC.

我們很高興在 UPGRADE-A 中完成劑量遞增並在第一季度開始劑量擴展，我們期待在今年下半年分享初步中期數據。在深入研究我們的其他臨床階段細胞毒性 ADC XMT-1660 之前，讓我們先了解一下 XMT-2056，這是我們的 HER2 定向免疫合成 STING 激動劑 ADC。

In March, we voluntarily suspended our Phase I trial of this product candidate following a Grade V serious adverse event, or SAE, that was deemed to be related to XMT-2056. The FDA then placed the trial on clinical hold. The SAE occurred in the second patient enrolled at the initial dose level in the dose escalation portion of the trial, and it was obviously quite unfortunate and unexpected. In recent weeks, we've received plasma PK and cytokine data for the 2 patients who are dosed in the trial prior to the clinical hold, and we're continuing to analyze these data. We're evaluating next steps for the program, and we'll prepare a response to the FDA's clinical hold letter. We will provide an update on our plans once they've been solidified.

3 月，在發生被認為與 XMT-2056 相關的 V 級嚴重不良事件 (SAE) 後，我們自願暫停了對該候選產品的 I 期試驗。隨後，FDA 將該試驗置於臨床暫停狀態。 SAE 發生在試驗劑量遞增部分以初始劑量水平入組的第二名患者中，這顯然是非常不幸和出乎意料的。最近幾週，我們收到了在臨床試驗前接受試驗給藥的 2 名患者的血漿 PK 和細胞因子數據，我們正在繼續分析這些數據。我們正在評估該計劃的後續步驟，我們將準備對 FDA 的臨床保留函做出回應。一旦我們的計劃得到鞏固，我們將提供更新。

Now let's turn to XMT-1660. Our Dolasynthen product candidate targeting B7-H4. We see B7-H4 as a particularly compelling target, given its high expression in a variety of tumors and its limited expression in healthy tissue. XMT-1660 is equipped with a precise target optimized drug-to-antibody ratio of 6 and our DolaLock payload with controlled bystander effects.

現在讓我們轉向 XMT-1660。我們針對 B7-H4 的 Dolasynthen 候選產品。我們認為 B7-H4 是一個特別引人注目的目標，因為它在多種腫瘤中高表達，而在健康組織中表達有限。 XMT-1660 配備了 6 的精確目標優化藥物抗體比和我們的 DolaLock 有效載荷，具有可控的旁觀者效應。

I'm happy to report that we are making good progress in the dose escalation portion of our multicenter Phase I trial, which is enrolling patients with breast, endometrial and ovarian cancers, and remain firmly on track to complete this portion of the trial later this year.

我很高興地報告，我們在多中心 I 期試驗的劑量遞增部分取得了良好進展，該試驗正在招募患有乳腺癌、子宮內膜癌和卵巢癌的患者，並堅定地按計劃在今年晚些時候完成這部分試驗年。

With that, let's turn the call over to our Chief Financial Officer, Brian DeSchuytner, for an update on our financials. Brian?

有了這個，讓我們把電話轉給我們的首席財務官 Brian DeSchuytner，了解我們財務的最新情況。布萊恩？

Thank you, Arvin. We are approaching our upcoming top line data readout in a strong financial position. Beyond the $170 million in upfront payments we received from collaborations over the past year, we're beginning to see a downstream benefit of those transactions in the form of initial discovery milestone revenues.

謝謝你，阿爾文。我們正在以強勁的財務狀況接近即將到來的頂線數據讀數。除了我們在過去一年中從合作中收到的 1.7 億美元預付款外，我們開始看到這些交易的下游收益，即初始發現里程碑收入的形式。

We ended the first quarter with approximately $274 million in cash, cash equivalents and marketable securities, and we also have a line of credit available to us. We expect our available funds to support our operating plan commitments into the second half of 2024, well past several potential milestones of significance. It should also be noted 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.

第一季度結束時，我們擁有大約 2.74 億美元的現金、現金等價物和有價證券，而且我們還有可用的信貸額度。我們預計我們的可用資金將支持我們到 2024 年下半年的運營計劃承諾，遠遠超過幾個潛在的重要里程碑。還應該注意的是，我們的現金跑道指南不假設我們當前合作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。

Now for a brief recap of our P&L for the first quarter. Net cash used in operating activities was approximately $29 million for the first quarter of 2023. Collaboration revenue for the first quarter of 2023 was $7.8 million compared to $2 million for the same period in 2022. The year-over-year increase was primarily related to our collaboration agreements with Merck KGaA and Asana. Research and development expenses for the first quarter of 2023 were $47.3 million, compared to $35.8 million for the same period in 2022, noncash R&D-related stock-based compensation expense for the first quarter of 2023 was $3.3 million. The year-over-year increase in R&D expenses was primarily related to higher manufacturing and clinical costs related to UpRi and an increase in head count. General and administrative expenses for the first quarter of 2023 were $18.3 million compared to $12.8 million during the same period in 2022.

現在簡要回顧一下我們第一季度的損益表。 2023 年第一季度用於經營活動的現金淨額約為 2900 萬美元。2023 年第一季度的合作收入為 780 萬美元，而 2022 年同期為 200 萬美元。同比增長主要與我們與 Merck KGaA 和 Asana 的合作協議。 2023 年第一季度的研發費用為 4730 萬美元，而 2022 年同期為 3580 萬美元，2023 年第一季度非現金研發相關的股票補償費用為 330 萬美元。研發費用的同比增長主要與 UpRi 相關的製造和臨床成本增加以及員工人數增加有關。 2023 年第一季度的一般和行政費用為 1830 萬美元，而 2022 年同期為 1280 萬美元。

Noncash G&A-related stock-based compensation expense for the first quarter of 2023 was $3.1 million. The year-over-year increase in G&A expenses was primarily related to increases in medical affairs and pre-commercial activities and head count. Mersana's net loss for the first quarter of 2023 was $56.2 million compared to a net loss of $47.3 million for the same period in 2022.

2023 年第一季度與非現金 G&A 相關的股票薪酬費用為 310 萬美元。 G&A 費用的同比增長主要與醫療事務和預商業活動以及員工人數的增加有關。 Mersana 2023 年第一季度的淨虧損為 5620 萬美元，而 2022 年同期為淨虧損 4730 萬美元。

Now I'll turn the call back over to Anna for a few closing remarks.

現在，我將把電話轉回給安娜，聽取一些結束語。

Thanks, Brian and Arvin. In summary, 2023 is lining up to be a transformative year for Mersana, and we are excited by all that lies ahead. We expect to report top line data for UPLIFT midyear following the major oncology conferences in June with a potential BLA submission plan for around the end of the year. We plan to significantly advance enrollment in our confirmatory trial UP-NEXT. We will also advance the dose expansion portion of UPGRADE-A and expect to report initial interim data from this trial in the second half of the year. Our team will continue to work to evaluate next steps related to our development of XMT-2056.

謝謝，布賴恩和阿爾文。總而言之，2023 年將成為 Mersana 變革的一年，我們對未來的一切感到興奮。我們預計將在 6 月的主要腫瘤學會議之後報告 UPLIFT 年中的頂線數據，並可能在年底左右提交 BLA 提交計劃。我們計劃大幅推進我們的確認試驗 UP-NEXT 的註冊。我們還將推進 UPGRADE-A 的劑量擴展部分，並期望在今年下半年報告該試驗的初步中期數據。我們的團隊將繼續努力評估與我們開發 XMT-2056 相關的後續步驟。

And finally, we plan to complete the dose escalation portion of our Phase I trial of XMT-1660 this year. We look forward to keeping you updated on all our progress. Now let's open the call to your questions. Operator, would you please provide the instructions?

最後，我們計劃在今年完成 XMT-1660 I 期試驗的劑量遞增部分。我們期待著讓您了解我們所有的進展。現在讓我們打開您的問題的電話。接線員，請提供說明好嗎？

(Operator Instructions) And today's first question comes from Brian Cheng with JPMorgan.

（操作員說明）今天的第一個問題來自摩根大通的 Brian Cheng。

Maybe just one on ASCO. Heading into ASCO, we saw that you have a presentation there on expressions of folate receptor alpha and also NaPi2b. So can you shed some light on what that presentation entail? And what should we be looking for there? And then I have a follow-up.

也許只有一個在 ASCO 上。在進入 ASCO 時，我們看到您在那裡做了關於葉酸受體 alpha 和 NaPi2b 表達的演講。那麼，您能否闡明該演示文稿的內容？我們應該在那裡尋找什麼？然後我有一個後續行動。

Thanks, Brian. This is Arvin. I can address that question. So we look forward to sharing information at ASCO and it's a data set that comes from our expansion cohort of our UpRi study, the Phase I study, and really, the purpose of it is to evaluate NaPi2b expression and folate receptor alpha expression, recognizing that in our other data sets, external to the one that we're presenting. We've described how NaPi2b is approximately 59% based on 400 tumor samples are relative to what we've seen from the FDA review of mirvetuximab where 29% was the positivity for folate receptor alpha.

謝謝，布萊恩。這是阿爾文。我可以解決這個問題。所以我們期待在 ASCO 上分享信息，它是來自我們 UpRi 研究擴展隊列的數據集，即第一階段研究，實際上，它的目的是評估 NaPi2b 表達和葉酸受體α表達，認識到在我們的其他數據集中，在我們展示的數據之外。我們已經描述了基於 400 個腫瘤樣本的 NaPi2b 是如何大約 59% 與我們從 FDA 對 mirvetuximab 的審查中看到的相關，其中 29% 是葉酸受體 alpha 的陽性。

Great. And maybe just one on UPLIFT top line. Heading into UPLIFT top line later this year -- later midyear, outside of overall response rate and duration of response, are there any additional efficacy measures that we could get at the top of the top line?

偉大的。也許只有一個在 UPLIFT 頂線。今年晚些時候進入 UPLIFT 頂線 - 年中晚些時候，除了總體反應率和反應持續時間之外，我們是否可以在頂線獲得任何額外的療效措施？

So I think, as we've said, the top line will be midyear after the June oncology conferences. And we will be showing overall response rate in the primary endpoint as well as the secondary endpoint, duration of response and of course, the key safety overview of the -- for the study.

所以我認為，正如我們所說，最重要的是在 6 月腫瘤學會議之後的年中。我們將展示主要終點的總體反應率以及次要終點、反應持續時間，當然還有研究的關鍵安全性概述。

And our next question today comes from Jonathan Chang with SVB Securities.

我們今天的下一個問題來自 SVB 證券公司的 Jonathan Chang。

First question, on the recent MIRASOL results, how does that impact your thinking on the UpRi opportunity and strategy?

第一個問題，關於最近的 MIRASOL 結果，這如何影響您對 UpRi 機會和戰略的思考？

We remain very excited about the UpRi opportunity, Jonathan. As you know, and this is evident from what we've seen from ImmunoGen, this is an area of high unmet medical need. There's a desperate need by physicians and patients for new agents and we remain very excited about UpRi. We've shown robust efficacy and a differentiated tolerability profile in the expansion cohort. And of course, as Arvin just alluded to, we have an agent that has a very significantly different prevalence and the overlap between folate high and NaPi2b high is quite limited. So there's a desperate need for new agents for these patients, and we hope UpRi will fill that gap.

喬納森，我們對 UpRi 的機會仍然感到非常興奮。如您所知，從我們從 ImmunoGen 中看到的情況可以明顯看出，這是一個醫療需求未得到滿足的領域。醫生和患者迫切需要新藥，我們對 UpRi 仍然感到非常興奮。我們在擴展隊列中顯示出強大的療效和差異化的耐受性。當然，正如 Arvin 剛才提到的那樣，我們有一種具有非常顯著不同流行率的藥物，葉酸高和 NaPi2b 高之間的重疊非常有限。因此，這些患者迫切需要新藥，我們希望 UpRi 能夠填補這一空白。

Got it. And second question, when could we see initial data from the B7-H4 program?

知道了。第二個問題，我們什麼時候可以看到 B7-H4 程序的初始數據？

What we've guided to, and I think Arvin mentioned on the call is that, we expect to complete dose escalation by the end of this year. Our dose escalation is proceeding as planned. And at that point, I think we will have not yet guided to data disclosures. But we're very excited about the program. We think this is a great target for an ADC and for our platform. So we'll make that decision on data disclosure as we approach completion of the dose escalation.

我們所指導的，我認為 Arvin 在電話會議上提到的是，我們希望在今年年底之前完成劑量升級。我們的劑量遞增正在按計劃進行。到那時，我認為我們還沒有指導數據披露。但我們對該計劃感到非常興奮。我們認為這是 ADC 和我們平台的一個很好的目標。因此，我們將在接近完成劑量遞增時就數據披露做出決定。

And our next question today comes from Colleen Kusy with Baird.

我們今天的下一個問題來自 Baird 的 Colleen Kusy。

On the UPLIFT readout that's coming up in midyear, would you expect to also report data in the overall patient population? And do you have any expectations on what you need to show in the NaPi2b low patient population to get a broad label?

在年中即將公佈的 UPLIFT 讀數中，您是否希望也報告整個患者群體的數據？您對需要在 NaPi2b 低患者人群中展示什麼才能獲得廣泛的標籤有什麼期望嗎？

Sure. Thanks, Colleen. So we do expect to share data not only in the NaPi2b population, which is our primary endpoint, but the overall population is a key secondary endpoint. So response rate in the key secondary end point could also support a broader indication. This alludes to actually your second question in relationship to what would you need to see in the low population.

當然。謝謝，科琳。因此，我們確實希望不僅在 NaPi2b 人群中共享數據，這是我們的主要終點，而且整個人群也是一個關鍵的次要終點。因此，關鍵次要終點的反應率也可以支持更廣泛的適應症。這實際上暗示了你的第二個問題，即你需要在低人口中看到什麼。

So keeping in mind that the benchmark for approval for both of these populations in discussion with FDA really is a single-agent chemotherapy response rates of 12%. Now that being said, the response rate in the overall population, we would imagine cannot not be completely driven by the NaPi2b positive population in order to generate that overall population response rate.

因此請記住，與 FDA 討論的這兩種人群的批准基準實際上是 12% 的單藥化療反應率。話雖這麼說，總人口的反應率，我們可以想像不能完全由 NaPi2b 陽性人口驅動，以產生總人口反應率。

Got it. That's helpful. And then on the UPGRADE data later this year, are you able to say roughly how many patients you'd expect and how much follow-up you'd expect to have?

知道了。這很有幫助。然後在今年晚些時候的 UPGRADE 數據上，你能大致說出你期望有多少患者以及你期望有多少後續行動嗎？

So we had announced last year that we had completed or -- with that we had approximately 12 patients within the dose escalation portion. And then in the first quarter of this year, we had indicated that we had completed dose escalation and initiated the expansion phase.

因此，我們去年宣布我們已經完成或 - 我們在劑量升級部分內有大約 12 名患者。然後在今年第一季度，我們表示我們已經完成了劑量升級並啟動了擴展階段。

So you can approximate in relationship to how many patients we would have within dose escalation, and the determination will be made just in relationship to how many patients would then be available for presentation in the second half of this year. That also gives you some sense of the follow-up that would be available for those patients.

因此，您可以近似地估計我們在劑量遞增期間會有多少患者，並且將根據今年下半年有多少患者可以進行展示來做出決定。這也讓您對這些患者可以進行的後續行動有所了解。

Got it. That's helpful. And then just last follow-up on the UPGRADE study that's reading out later. So would the focus there be mainly on safety? Or can you kind of help us set a bar for efficacy in that readout?

知道了。這很有幫助。然後只是對升級研究的最後一次跟進，稍後會讀出。那麼重點會不會主要放在安全上呢？或者你能幫我們設定一個讀數的效率標準嗎？

Sure. So the primary focus absolutely is safety is a Phase I study, and it is really driven off the premise that UpRi provides a differentiated profile with nonoverlapping toxicities affording a great opportunity to combine with standard of care platinum for instance.

當然。因此，主要重點絕對是安全性是一項 I 期研究，它確實脫離了 UpRi 提供具有非重疊毒性的差異化概況的前提，從而提供了與標準護理鉑金相結合的絕佳機會。

In addition to that, obviously, being able to continue the UpRi portion of it after completion of the 6 cycles of combination into the monotherapy. So safety will be the primary focus of this presentation, recognizing that the follow-up to get into the maintenance may not be sufficient at that time point. We will plan to present also efficacy for the available information, but it's in the context, obviously, recognizing safety is the primary focus.

除此之外，很明顯，在完成 6 個週期的聯合治療後，能夠繼續使用 UpRi 部分進入單一療法。因此，安全將是本次演講的主要重點，認識到進入維護的後續行動在那個時間點可能還不夠。我們將計劃還展示可用信息的有效性，但在上下文中，顯然，認識到安全是主要焦點。

(Operator Instructions) Our next question today comes from Kaveri Pohlman with BTIG.

（操作員說明）我們今天的下一個問題來自 BTIG 的 Kaveri Pohlman。

For the upcoming ASCO data for expression studies, is that specifically for platinum-resistant population, do you expect to see any changes in NaPi2b expression or the overlap when you move to earlier lines?

對於即將發布的表達研究的 ASCO 數據，是否專門針對鉑類耐藥人群，當您轉向早期細胞係時，您是否期望看到 NaPi2b 表達或重疊的任何變化？

Thanks for the question, Kaveri. So just for context, obviously, we want to share the presentation for ASCO. But as I mentioned earlier, this will be on a data set that comes from our Phase I study. And so that included primarily platinum-resistant ovarian cancer patients. There was a proportion of patients that were fourth line plus that could have been platinum sensitive. But again, these were a minority of the patients.

謝謝你的問題，Kaveri。因此，很明顯，就上下文而言，我們想分享 ASCO 的演示文稿。但正如我之前提到的，這將基於來自我們第一階段研究的數據集。因此，這主要包括對鉑耐藥的卵巢癌患者。有一部分患者為四線以上，可能對鉑敏感。但同樣，這些只是少數患者。

But to your second point in relationship to the prevalence of NaPi2b, we shared actually a variety of different presentations in the past from tumor banks, from our own internal studies that support the consistency of NaPi2b expression by line of therapy as well as from a local and metastatic site perspective. There, I'll remind folks that 59% was the NaPi2b positivity when looking at one of the largest -- the largest tumor bank analysis of individual tissue samples of approximately 400 samples.

但是關於你關於 NaPi2b 流行的第二點，我們實際上分享了過去來自腫瘤庫的各種不同的介紹，來自我們自己的內部研究，這些研究支持治療線以及當地的 NaPi2b 表達的一致性和轉移部位的觀點。在那裡，我會提醒人們，當查看最大的一個——最大的腫瘤庫分析時，NaPi2b 是 59% 的陽性，對大約 400 個樣本的個體組織樣本進行了分析。

That's very helpful. And for the UP-NEXT study, it's a novel design, but any insight you could provide on addressable patient population, how different it is from the platinum-resistant market? And in terms of benchmarks for PFS, what would you expect out of the placebo arm?

這很有幫助。對於 UP-NEXT 研究，這是一個新穎的設計，但您可以提供有關可尋址患者人群的任何見解，它與鉑耐藥市場有何不同？就 PFS 的基準而言，您對安慰劑組有何期望？

So maybe Arvin can talk to the placebo arm and the potential benefit here. As for the size of the market, we have not given specific numbers, but we do believe that this trial will bring us to a large area, unmet medical need, potentially larger than platinum-resistant with a positive UP-NEXT trial.

所以也許 Arvin 可以談談安慰劑組和這裡的潛在好處。至於市場規模，我們沒有給出具體數字，但我們確實相信，這項試驗將把我們帶到一個大面積、未滿足的醫療需求，可能比 UP-NEXT 試驗陽性的鉑耐藥更大。

And maybe just before I jump into the placebo effect, I'll just comment that given the emerging landscape of the PARP inhibitors, with the recent FDA changes, where PARP inhibitors are no longer approved in the -- or restricted primarily to the BRCA and HRD positives, we see that actually as increasing the unmet need in that recurrent platinum maintenance setting -- in platinum-sensitive maintenance setting.

也許就在我進入安慰劑效應之前，我只想評論一下，鑑於 PARP 抑製劑的新興前景，隨著最近 FDA 的變化，PARP 抑製劑不再被批准用於 - 或主要限於 BRCA 和HRD 積極因素，我們認為這實際上增加了該週期性鉑金維護設置中未滿足的需求——在對鉑金敏感的維護設置中。

Kaveri, just to your second question as far as the activity of placebo. One of the best benchmarks maybe the NOVA study. So it's a study of a PARP inhibitor in the recurrent platinum-sensitive maintenance setting. And there, the placebo arm had a performance of PFS of approximately 4.5 months. But I do want to provide context to that figure because that was a study performed in an earlier time period where patients may not have received or would not have actually received prior PARP or bev in that era of where the study was conducted.

Kaveri，關於安慰劑活性的第二個問題。最好的基準之一可能是 NOVA 研究。所以這是對 PARP 抑製劑在復發性鉑敏感維持治療中的研究。在那裡，安慰劑組的 PFS 表現約為 4.5 個月。但我確實想為這個數字提供背景，因為這是一項在較早時期進行的研究，在進行研究的那個時代，患者可能沒有接受過或實際上不會接受過 PARP 或 bev。

In addition to that, this patient population was less heavily pretreated and platinum-refractory because they did not include stable disease patients to the prior platinum therapy, in acknowledgment that the PARP inhibitor and platinum mechanism of action has sufficient similarity that they did not want to include stable disease patients for their study as opposed to in UP-NEXT, where we're doing for these patients.

除此之外，該患者群體的預處理和鉑類耐藥性較低，因為他們不包括先前鉑類治療的穩定疾病患者，承認 PARP 抑製劑和鉑類作用機制具有足夠的相似性，他們不想在他們的研究中包括病情穩定的患者，而不是在我們為這些患者做的 UP-NEXT 中。

Got it. And maybe the last one on B7-H4 ADC. From the competitive landscape standpoint and from your experience with UpRi and 1529, can you tell us what advantages the single-species ADCs provide?

知道了。也許是 B7-H4 ADC 上的最後一個。從競爭格局的角度以及您使用 UpRi 和 1529 的經驗來看，您能告訴我們單一物種 ADC 提供哪些優勢嗎？

We didn't hear the second part of your question. You're asking for the differentiation versus other B7-H4 ADCs, Kaveri, was that the question?

我們沒有聽到你問題的第二部分。你問的是與其他 B7-H4 ADC 的區別，Kaveri，是這個問題嗎？

Yes. And you have intensive experience with UpRi and 1529, which was also a single-species ADCs. So I just wanted to get some sense what advantages the homogeneous ADCs provides.

是的。你對 UpRi 和 1529 有豐富的經驗，這也是一個單一物種的 ADC。所以我只是想了解一下同構 ADC 提供了哪些優勢。

Sure. I can start and if the team wants to add to that. So I mean, first off, we're very excited about B7-H4. We think it's a good target. Given the competitive landscape, I would argue that others agree with us in relationship to that. Before diving into that, actually, let me just clarify. We do actually have extensive knowledge with the Dolaflexin molecule and its differentiated safety profile, given that it's the same payload that's utilized in UpRi.

當然。我可以開始，如果團隊想加入的話。所以我的意思是，首先，我們對 B7-H4 感到非常興奮。我們認為這是一個很好的目標。鑑於競爭格局，我認為其他人同意我們的看法。實際上，在深入探討之前，讓我澄清一下。我們確實對 Dolaflexin 分子及其差異化的安全性有廣泛的了解，因為它與 UpRi 中使用的有效載荷相同。

Again, without the severe neutropenias, the ocular toxicities or the neuropathies, we did evaluate it also in the 1592 program. I just wanted to clarify that, that was a Dolasynthen molecule with the same payload, just to clarify, it wasn't 1529. Now with that being said, we are excited about B7-H4 because it does differentiate relative to -- and I'll flag 2 different companies that are also developing B7-H4.

同樣，在沒有嚴重的中性粒細胞減少症、眼部毒性或神經病的情況下，我們也在 1592 計劃中對其進行了評估。我只是想澄清一下，那是一個具有相同有效載荷的 Dolasynthen 分子，只是為了澄清一下，它不是 1529。話雖如此，我們對 B7-H4 感到興奮，因為它確實相對於 - 而且我將標記 2 個不同的公司，它們也在開發 B7-H4。

So Seagen is developing a B7-H4 molecule. But we have a DAR of -- a homogeneous DAR of 6, alluding to sort of the point you're raising. And we believe that through our preclinical data that the DAR of 6 did have differential benefit from the standpoint of greater efficacy when looking at our preclinical models. In addition to that, we do expect that from a payload perspective, it will have that differentiated safety profile relative to vcMMAE the procedure molecules being developed at, where they also have a lower DAR of approximately 2.5. So I think that addresses your question just as far as the differentiated profile.

所以 Seagen 正在開發 B7-H4 分子。但是我們有一個 DAR 是——一個 6 的同質 DAR，暗示了你提出的某種觀點。我們相信，通過我們的臨床前數據，在查看我們的臨床前模型時，從更高療效的角度來看，6 的 DAR 確實具有不同的益處。除此之外，我們確實希望從有效載荷的角度來看，它與正在開發的程序分子 vcMMAE 相比具有差異化的安全性，它們的 DAR 也較低，約為 2.5。因此，我認為就差異化配置文件而言，這可以解決您的問題。

Yes, that's very helpful. And yes, I meant 92 instead of 29, sorry about that.

是的，這很有幫助。是的，我的意思是 92 而不是 29，抱歉。

Yes. No problem.

是的。沒問題。

And our next question today comes from Ashiq Mubarack with Citi.

我們今天的下一個問題來自花旗的 Ashiq Mubarack。

Anna, you made some comments related to building out commercial infrastructure in the past quarter. Can you comment at all on the size and the reach of the sales force for UpRi that you're building out? And maybe any general commentary on how much of an educational UPLIFT you think there needs to be with the NaPi2b biomarker testing in the sort of real-world setting?

安娜，你在上個季度發表了一些與構建商業基礎設施相關的評論。您能否對您正在為 UpRi 建立的銷售隊伍的規模和範圍發表評論？也許任何關於您認為在現實世界環境中進行 NaPi2b 生物標誌物測試需要多少教育提升的一般性評論？

So our commercial efforts are very much focused on prelaunch activities, we're some ways away from really defining the exact size and details of the sales force. So let me focus on what we are doing now. We have a very small, but impactful medical affairs group that is really working with investigators to increase the awareness of the importance of NaPi2b as a biomarker and to educate on UpRi as a potential therapy in ovarian cancer.

因此，我們的商業努力非常專注於啟動前活動，我們距離真正定義銷售隊伍的確切規模和細節還有一些距離。因此，讓我專注於我們現在正在做的事情。我們有一個非常小但有影響力的醫療事務小組，它真正與研究人員合作，以提高人們對 NaPi2b 作為生物標誌物的重要性的認識，並就 UpRi 作為卵巢癌的潛在療法進行教育。

We have really a handful of people with deep ovarian cancer commercial expertise that are really preparing the market plans and ensuring that our diagnostic is available on day 1. So that is the effort. A very small group of people has, I believe, been very impactful in ensuring all the work is done for us to be ready with positive data, with the BLA and then potentially an upcoming approval to be able to build out that effort.

我們確實有少數具有深厚卵巢癌商業專業知識的人正在真正準備市場計劃並確保我們的診斷在第一天就可用。這就是努力。我相信，一小群人在確保完成所有工作以準備好獲得積極數據、BLA 以及可能即將獲得的批准以加強這項工作方面發揮了非常大的影響。

Got it. That's really helpful. If I can ask one more also on the commercial plan. I think in the past, you've alluded to your plan to partner UpRi in Europe and in other regions globally. And I'm just wondering if you can remind us why that's the right move? I think Immunogen made some commentary last week related to the idea that the European market is actually pretty concentrated around a limited number of centers, which maybe covers the majority of the market. So I'm wondering why if you think -- or thinking about the European opportunity in a similar or a very different way given you're planning to partner?

知道了。這真的很有幫助。如果我可以在商業計劃上再問一個。我想在過去，你曾提到過在歐洲和全球其他地區與 UpRi 合作的計劃。我只是想知道你是否可以提醒我們為什麼這是正確的舉動？我認為 Immunogen 上週發表了一些評論，認為歐洲市場實際上非常集中在有限數量的中心周圍，這些中心可能涵蓋了大部分市場。所以我想知道為什麼如果你考慮 - 或者考慮到你計劃合作的方式以類似或非常不同的方式考慮歐洲機會？

Yes. Our thoughts are really based on extensive experience across the biotech industry, really investing in an infrastructure in Europe, although eventually might be -- my playoff is a significant investment. And as you're aware, getting reimbursement in Europe always takes time. So by the time that European infrastructure becomes cash flow positive, it takes a lot longer to get there than in the U.S.

是的。我們的想法實際上是基於整個生物技術行業的廣泛經驗，真正投資於歐洲的基礎設施，儘管最終可能是——我的季后賽是一項重大投資。如您所知，在歐洲獲得報銷總是需要時間。因此，當歐洲基礎設施的現金流轉為正值時，比美國要花更長的時間才能到達那裡。

And I think that's what's driving our thinking, which, of course, will be refined as we get top line data, that will be further refined. But I think history will say that small biotech companies that expand to both the U.S. and Europe can -- would require a significant investment before that commercial infrastructure can really begin to be cash flow positive.

而且我認為這就是推動我們思考的原因，當然，隨著我們獲得頂級數據，我們會進一步完善我們的想法，這將進一步完善。但我認為歷史會證明，向美國和歐洲擴張的小型生物技術公司可以——在商業基礎設施真正開始產生正現金流之前需要大量投資。

And our next question comes from Boris Peaker with Cowen.

我們的下一個問題來自 Boris Peaker 和 Cowen。

First question on the UPLIFT study. Can you set expectations for duration of response? And if that is something that you've discussed with the FDA what the agency may be looking for in terms of duration of response?

關於 UPLIFT 研究的第一個問題。你能設定響應持續時間的期望值嗎？如果這是您與 FDA 討論過的事情，該機構可能會在響應持續時間方面尋找什麼？

Thanks for the question, Boris. So in discussions with FDA, we've aligned that response rate is the primary endpoint for evaluation of efficacy and that's 12% based upon the multiple Phase III studies that we've described in the past. Duration of response certainly will be expected. It will be in the context again of the overall efficacy and safety profile on that, it will be taken into context.

謝謝你的問題，鮑里斯。因此，在與 FDA 的討論中，我們一致認為反應率是評估療效的主要終點，根據我們過去描述的多項 III 期研究，反應率是 12%。響應的持續時間當然是可以預料的。它將再次在整體有效性和安全性的背景下，將被納入背景。

Great. And maybe in terms of baseline characteristic, you mentioned that you allowed baseline Grade II, I guess, lower neuropathy in the UPLIFT trial, while these patients were excluded from SORAYA and MIRASOL. Just curious, can you comment what fraction of these platinum-refractory patients have this baseline neuropathy?

偉大的。也許就基線特徵而言，你提到在 UPLIFT 試驗中你允許基線 II 級，我猜，較低的神經病變，而這些患者被排除在 SORAYA 和 MIRASOL 之外。只是好奇，您能評論一下這些鉑難治性患者中有多少患有這種基線神經病變嗎？

So we know that most of the patients, actually, if not all, of the patients that become platinum-resistant will have received an agent that can induce neuropathy. Given that Taxol is a heavy offender and other chemotherapies certainly contribute to that. I don't have the numbers specifically for the expansion data available in reference to that.

所以我們知道，大多數對鉑產生耐藥性的患者，實際上，如果不是全部，都接受了一種可以誘發神經病變的藥物。鑑於紫杉醇是一個嚴重的罪犯，其他化學療法肯定會對此有所貢獻。我沒有專門針對可參考的擴展數據的數字。

But based on what I just described earlier is that, we do expect a fair proportion of patients to have some degree of neuropathy. That could obviously be impacted if they were to receive further therapy, that could cause neuropathy, whereby with UpRi, we have not seen the severe neuropathies.

但根據我剛才描述的情況，我們確實預計相當一部分患者會出現某種程度的神經病變。如果他們接受進一步的治療，這顯然會受到影響，這可能會導致神經病變，而對於 UpRi，我們還沒有看到嚴重的神經病變。

And our next question comes from Asthika Goonewardene with Truist.

我們的下一個問題來自 Asthika Goonewardene 和 Truist。

So the MIRASOL study, the ORR supplied is positively getting to the 40%-plus range. And I guess, one could attribute that to being the start of recruiting a homogenous population than the Phase I and essentially a less sicker patient population than SORAYA. You guys have already set a very high bar with ORR in your Phase I expansion work. So would it be unreasonable to expect your ORR to look better on UPLIFT as well?

因此，MIRASOL 研究提供的 ORR 正達到 40% 以上的範圍。我想，人們可以將其歸因於招募同質人群的開始，而不是第一階段，並且基本上比 SORAYA 病情更輕的患者人群。你們已經在第一階段擴展工作中為 ORR 設定了很高的標準。那麼，期望您的 ORR 在 UPLIFT 上也看起來更好是不合理的嗎？

Well, thanks for the question. We saw robust activities expansion cohort, particularly with the 36-milligram per meter square. But I think the differences in overall response rate between MIRASOL and SORAYA do serve as a reminder that the type and level of patient pretreatment can influence impact.

好吧，謝謝你的提問。我們看到了強勁的活動擴張隊列，特別是每平方米 36 毫克。但我認為 MIRASOL 和 SORAYA 之間總體反應率的差異確實提醒我們，患者預處理的類型和水平會影響影響。

And again, as Arvin mentioned on the call, we do have a population that is more heavily pretreated than SORAYA and definitely even more heavily pretreated than MIRASOL. So I think we'll have to wait and see the results mid-year, but we're confident based on the robust activity we saw in the expansion cohort.

再一次，正如 Arvin 在電話中提到的那樣，我們確實有一個比 SORAYA 更嚴格預處理的人群，而且肯定比 MIRASOL 更嚴格預處理。所以我認為我們將不得不等待年中的結果，但我們有信心基於我們在擴展隊列中看到的強勁活動。

Great. And then maybe just two quick questions. Do you plan to report the UPGRADE-A data at a medical meeting? Or would that be more geared towards investment community? And then on the diagnostic test, our KOL suggested that there were some bottlenecks faced with the diabetic test for mirvetuximab with one of the centers in particular, take a little bit of a while to turn the test around. What have you learned from that from your competitor experience? And what are you doing to kind of make sure that you don't run into the same issues.

偉大的。然後可能只是兩個簡單的問題。您打算在醫學會議上報告 UPGRADE-A 數據嗎？還是更適合投資界？然後在診斷測試中，我們的 KOL 建議，特別是其中一個中心的 mirvetuximab 糖尿病測試面臨一些瓶頸，需要一點時間來扭轉測試。您從競爭對手的經歷中學到了什麼？你在做什麼來確保你不會遇到同樣的問題。

On the diagnostic, we're working with our diagnostic partner to ensure that the test is available on day 1 and that we appropriately prepare in terms of supply of reagents to ensure there is no disruption in availability of the test. And what was the other question? The other -- was there a second question?

在診斷方面，我們正在與我們的診斷合作夥伴合作，以確保在第一天就可以進行測試，並且我們在試劑供應方面進行了適當的準備，以確保測試的可用性不會中斷。另一個問題是什麼？另一個——還有第二個問題嗎？

Yes, I can address the first question. Just as far as UPGRADE-A, we've indicated that we'll share the data in the second half of this year. We haven't expressed sort of what type of forum that will be in, and we'll disclose that at the appropriate time.

是的，我可以回答第一個問題。就UPGRADE-A而言，我們已經表示我們將在今年下半年共享數據。我們還沒有說明將在什麼類型的論壇中，我們會在適當的時候披露。

And our next question today comes from David Nierengarten with Wedbush Securities.

我們今天的下一個問題來自 Wedbush Securities 的 David Nierengarten。

And maybe as a follow-up on diagnostic or the testing question. Just if you had any particularly updated thoughts on how physicians would -- when presented with a patient in earlier lines -- or I guess, in any line of setting, react to the patients, should they test with folate first? Are they going to do both tests, do you think, kind of how -- and treat appropriately, kind of how do you see that evolving with the positive MIRASOL results?

也許作為診斷或測試問題的後續行動。如果您對醫生在較早階段與患者接觸時會如何做出任何特別更新的想法，或者我猜想，在任何情況下，對患者的反應，他們應該先用葉酸進行測試嗎？他們是否會進行這兩項測試，你認為，如何 - 並適當地對待，你如何看待隨著積極的 MIRASOL 結果而演變？

We are very encouraged by the testing that is taking place with folate positive patients. And we believe that what will happen once both agents are in the market is that when a patient is diagnosed with ovarian cancer, they will undergo a set of tests that will include both folate and NaPi2b. And that is the desired sort of state of affairs in the future. And I think the uptake we've seen on the following test is encouraging that, that will be -- that will be the case. And David, we are definitely working to make sure that our test is available on day 1 after launch for anyone at any stage who wants to take the test, at any stage of their disease.

我們對正在對葉酸陽性患者進行的檢測感到非常鼓舞。我們相信，一旦這兩種藥物上市，將會發生的事情是，當患者被診斷出患有卵巢癌時，他們將接受一系列測試，其中包括葉酸和 NaPi2b。這就是未來所希望的事態。而且我認為我們在以下測試中看到的吸收令人鼓舞，那就是 - 情況將會如此。大衛，我們肯定會努力確保我們的測試在發布後的第一天就可以提供給任何想要接受測試的人，無論他們處於疾病的任何階段。

(Operator Instructions) Our next question is a follow-up from Colleen Kusy with Baird.

（操作員說明）我們的下一個問題是 Colleen Kusy 和 Baird 的後續問題。

Just one more. So on the UPLIFT readout and kind of understanding that the patient pretreatment is going to impact the ORR, can you remind us how many patients in the dose expansion were fourth line or later. And would you expect that proportion of patients to be similar or different in the UPLIFT study?

還有一個。因此，關於 UPLIFT 讀數和對患者預處理將影響 ORR 的理解，您能否提醒我們劑量擴展中有多少患者是第四線或更晚的。您認為 UPLIFT 研究中的患者比例會相似還是不同？

Thanks for the question, Colleen. So approximately 33% of the patients in the expansion portion of the Phase I study for UpRi was fourth line or later. Obviously, we'll disclose broader demographics at the top line per se. But for context, we enrolled in the U.S. as well as in the EU for the UPLIFT study globally in relationship with the UPLIFT study, but we would expect practice patterns to be relatively similar in the platinum-resistant space.

謝謝你的問題，科琳。因此，在 UpRi I 期研究的擴展部分中，大約 33% 的患者是第四線或更晚的。顯然，我們將在頂線本身披露更廣泛的人口統計數據。但就背景而言，我們在美國和歐盟註冊了與 UPLIFT 研究相關的全球 UPLIFT 研究，但我們預計在鉑耐藥領域的實踐模式相對相似。

Colleen, I would add one other point. The fact that we have enrolled so robustly in UPLIFT, I think, it might give us an opportunity to look at how pretreatment impacts overall response in sub-group analysis and really help us better under the profile of the agent.

科琳，我還要補充一點。事實上，我們在 UPLIFT 中的參與度如此之高，我認為，這可能會讓我們有機會了解預處理如何影響亞組分析中的整體反應，並真正幫助我們更好地了解代理人的情況。

And ladies and gentlemen, this concludes our question-and-answer session. I'd like to turn the conference back over to Anna Protopapas for any closing remarks.

女士們，先生們，我們的問答環節到此結束。我想將會議轉回給 Anna Protopapas，聽取任何閉幕詞。

Thank you, operator, and thanks to all those who listened in and for your continued support. We are looking forward to participating in the Bank of America Healthcare Conference tomorrow, sharing several poster presentations at ASCO next month, and presenting at the Jefferies Healthcare Conference a few days later. Hope to see many of you at those events. Enjoy the rest of the day.

謝謝接線員，也感謝所有收聽的人和您一直以來的支持。我們期待著參加明天的美國銀行醫療保健會議，下個月在 ASCO 上分享幾張海報，並在幾天后的 Jefferies 醫療保健會議上發表演講。希望在這些活動中見到你們中的許多人。享受剩下的一天。

Thank you. Ladies and gentlemen, this concludes today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines, and have a wonderful day.

謝謝。女士們，先生們，今天的電話會議到此結束。感謝大家出席今天的演講。您現在可以斷開線路，度過美好的一天。