ImmunoGen Inc (IMGN) 2023 Q3 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to ImmunoGen's Third Quarter 2023 Financial and Operating Results Conference Call. Today's conference is being recorded. At this time, I'd like to turn the call over to Anabel Chan, Head of Investor Relations. Please go ahead.

早安，女士們、先生們，歡迎參加ImmunoGen 2023 年第三季財務與營運業績電話會議。今天的會議正在錄製中。現在，我想將電話轉給投資人關係主管 Anabel Chan。請繼續。

Good morning, and thank you for joining today's call. Earlier today, we issued a press release that includes a summary of our recent operating progress and third quarter financial results. This press release, a recording of this call and an updated corporate deck can be found under the Investors & Media section of our website at immunogen.com.

早安，感謝您參加今天的電話會議。今天早些時候，我們發布了一份新聞稿，其中包括我們最近的營運進度和第三季財務業績的摘要。本新聞稿、本次電話會議錄音以及更新的公司資料可在我們網站immunogen.com 的投資者與媒體部分找到。

With me today are Mark Enyedy, our President and CEO; and Isabel Kalofonos, our Chief Commercial Officer; Michael Vasconcelles, our EVP of Research, Development and Medical Affairs; and Lauren White, our CFO.

今天與我在一起的有我們的總裁兼執行長 Mark Enyedy；以及我們的首席商務官 Isabel Kalofonos； Michael Vasconcelles，我們的研究、發展和醫療事務執行副總裁；和我們的財務長勞倫·懷特（Lauren White）。

During today's call, we will review recent progress for the business, our financial results and highlight upcoming anticipated events. We will be making forward-looking statements based on our current expectations and beliefs. These statements are subject to risks and uncertainties, and our actual results may differ materially. Please consult the risks outlined in our press release issued this morning in the Risk Factors section of our most recent annual report on Form 10-K and quarterly report on Form 10-Q and in our other SEC filings, which are available at sec.gov and immunogen.com. With that, I'll turn the call over to Mark.

在今天的電話會議中，我們將回顧最近的業務進展、我們的財務業績，並重點介紹即將發生的預期事件。我們將根據我們目前的期望和信念做出前瞻性陳述。這些陳述存在風險和不確定性，我們的實際結果可能存在重大差異。請查閱我們今天上午發布的新聞稿中概述的風險，該新聞稿位於我們最新的10-K 表年度報告和10-Q 表季度報告的風險因素部分，以及我們其他SEC 備案文件（可在sec. gov 上取得）和immunogen.com。這樣，我會將電話轉給馬克。

Thanks, Anabel. Good morning, everyone, and thank you for joining us today. This has been another productive quarter for ImmunoGen, highlighted by the ongoing exemplary execution of the commercial launch for ELAHERE in the U.S., progress made towards both geographic and label expansion for ELAHERE and the advancement of our portfolio.

謝謝，安娜貝爾。大家早安，感謝您今天加入我們。對於ImmunoGen 來說，這是另一個富有成果的季度，突出表現在 ELAHERE 在美國商業發布的持續示範執行、ELAHERE 的地理和標籤擴張方面取得的進展以及我們產品組合的進步。

Starting with the commercial update. We delivered a strong quarter with ELAHERE generating just over $105 million in net sales, resulting in over $210 million in revenue year-to-date, which puts us on track with one of the most successful oncology launches in a decade. This performance is driven by a combination of factors, including strong adoption of FR alpha testing and corresponding product ordering in a population with high unmet need with robust uptake in our labeled indication across both academic and community settings as well as discretionary use in a broader patient population based on NCCN guidelines, including use of ELAHERE monotherapy in later lines and in combination with bevacizumab. Rapid achievement of broad access and reimbursement increased breadth and depth of prescribing, driven in part by penetration into priority accounts and increased awareness of ELAHERE driven by engagement by our medical affairs team, the compelling data for MIRASOL and positive physician and patient experiences.

從商業更新開始。我們的季度表現強勁，ELAHERE 的淨銷售額略高於 1.05 億美元，年初至今收入超過 2.1 億美元，這使我們有望成為十年來最成功的腫瘤產品之一。這一表現是由多種因素推動的，包括在需求未滿足的人群中大力採用FR α 測試和相應的產品訂購，在學術和社區環境中廣泛採用我們的標籤適應症，以及在更廣泛的患者中酌情使用基於 NCCN 指南的人群，包括在後期治療中使用 ELAHERE 單藥治療以及與貝伐單抗聯合治療。快速實現廣泛的准入和報銷增加了處方的廣度和深度，部分原因是滲透到優先帳戶以及我們的醫療事務團隊的參與、MIRASOL 令人信服的數據以及積極的醫生和患者體驗推動的ELAHERE 意識的提高。

Looking forward, we expect continued growth, albeit at a moderating pace supported by continued focus on execution with respect to our launch imperatives, a strong and growing prescriber base, and ELAHERE becoming the medicine of choice for patients with FR alpha-positive disease. Isabel will have more to say about our current and future business in a moment.

展望未來，我們預計會持續成長，儘管成長速度會放緩，這得益於我們繼續專注於執行我們的上市要求、強大且不斷增長的處方者基礎，以及ELAHERE 成為FR α 陽性疾病患者的首選藥物。伊莎貝爾稍後將詳細介紹我們目前和未來的業務。

As we aim to expand the geographic footprint for ELAHERE and look to bring this novel ADC to patients globally, we are pleased to share that the EMA has accepted our marketing application to support potential European approval and our partner Huadong received acceptance of the NDA in China. In addition, we announced a collaboration with Takeda to develop and commercialize ELAHERE in Japan and submitted a supplemental BLA to FDA to support the conversion of the accelerated approval of ELAHERE to full approval here in the U.S.

由於我們的目標是擴大ELAHERE 的地理覆蓋範圍，並希望將這種新型ADC 帶給全球患者，我們很高興地宣布，EMA 已接受我們的行銷申請，以支持潛在的歐洲批准，並且我們的合作夥伴華東在中國已接受NDA 。此外，我們還宣布與武田合作在日本開發和商業化 ELAHERE，並向 FDA 提交了補充 BLA，以支持 ELAHERE 在美國從加速批准轉變為全面批准。

In step with our commercial efforts, we are advancing the broader ELAHERE development program to support label expansion into platinum-sensitive disease and to position ELAHERE as the combination agent of choice in ovarian cancer. In this context, we are pleased to share that our PICCOLO Phase II trial evaluating ELAHERE monotherapy in platinum-sensitive ovarian cancer has met its primary endpoint of objective response rate. Noting that PICCOLO is ongoing and patients are continuing to receive ELAHERE, to date, we've observed no new safety signals in this patient population. These data represent an important step towards expanding ELAHERE into the platinum-sensitive setting, and Mike will discuss these data in more detail shortly. Turning briefly to the rest of the pipeline.

隨著我們的商業努力，我們正在推進更廣泛的 ELAHERE 開發計劃，以支持標籤擴展到鉑類敏感疾病，並將 ELAHERE 定位為卵巢癌的首選組合藥物。在這種背景下，我們很高興地與大家分享，我們評估 ELAHERE 單藥治療鉑敏感卵巢癌的 PICCOLO II 期試驗已經達到了客觀緩解率的主要終點。注意到 PICCOLO 正在進行中並且患者繼續接受 ELAHERE，迄今為止，我們在該患者群體中沒有觀察到新的安全訊號。這些數據代表著將 ELAHERE 擴展到鉑敏感環境的重要一步，Mike 將很快更詳細地討論這些數據。簡單地轉向管道的其餘部分。

In our second pivotal program, PVEK, we look forward to reporting data from our PVEK triplet in frontline AML later this year at ASH, and we are on track with top line data from the pivotal frontline de novo cohort in BPDCN expected in 2024. In addition, IMGC936 and IMGN151 are progressing, and we remain focused on reinvesting in our research capabilities and expanding our pipeline.

在我們的第二個關鍵計劃 PVEK 中，我們期待今年稍後在 ASH 報告一線 AML 中的 PVEK 三聯體數據，並且我們預計將於 2024 年獲得 BPDCN 中關鍵一線 de novo 隊列的頂線數據。此外，IMGC936和IMGN151正在取得進展，我們仍然專注於對我們的研究能力進行再投資並擴大我們的產品線。

Lastly, I'm pleased to report that we strengthened our leadership team with the recent appointment of Lauren White as Chief Financial Officer; and commensurate with our expanding commitment to continued innovation of our ADC platform, we welcome Heather Huet as Chief Scientific Officer. With an experienced management team in place and a strong balance sheet, we are well positioned to expand the commercial opportunity for ELAHERE and in parallel, continuing to advance and invest in our pipeline.

最後，我很高興地向大家報告，最近任命勞倫懷特 (Lauren White) 為首席財務官，我們加強了我們的領導團隊；與我們不斷擴大對 ADC 平台持續創新的承諾相稱，我們歡迎 Heather Huet 擔任首席科學長。憑藉經驗豐富的管理團隊和強大的資產負債表，我們有能力擴大 ELAHERE 的商業機會，同時繼續推動和投資我們的產品線。

With that, I'll turn the call over to Isabel to cover our commercial progress. Isabel?

這樣，我會將電話轉給伊莎貝爾，介紹我們的商業進展。伊莎貝爾？

Thank you, Mark. The commercial team built upon the strong momentum established in the first half of the year and delivered another strong quarter as we continue to make progress towards positioning ELAHERE as the standard of care for folate receptor alpha positive ovarian cancer. In the third quarter, we saw a 35% sequential growth versus the prior quarter. We are pleased with our performance since launch and believe it is due to a combination of 4 key factors, including: a strong adoption in an area of high unmet need; rapid access and reimbursement coverage; the solid execution of our commercial customer-facing teams; and increased physician experience and awareness of the benefits this novel treatment brings to patients with advanced ovarian cancer.

謝謝你，馬克。隨著我們繼續在將 ELAHERE 定位為葉酸受體 α 陽性卵巢癌的護理標準方面取得進展，商業團隊在上半年建立的強勁勢頭的基礎上，又實現了另一個強勁的季度。第三季度，我們看到與上一季相比較上季成長了 35%。我們對自推出以來的表現感到滿意，並相信這是由於 4 個關鍵因素的綜合作用，包括： 在需求未滿足的領域得到廣泛採用；快速取得和報銷範圍；我們面向商業客戶的團隊的紮實執行力；增加醫生的經驗和對這種新療法對晚期卵巢癌患者帶來的好處的認識。

Let me take some time to address each of these key factors in more detail. First, let me share some insight into the dynamics observed while launching into an area of high unmet need. Starting with the identification of eligible patients, almost a year into our launch, we have seen the overall awareness for FR alpha testing increase and rapid adoption of the FOLR1 diagnostics being incorporated as a standard component of the initial panel conducted on newly diagnosed patients and for patients moving to the next line of therapy.

讓我花一些時間更詳細地討論每個關鍵因素。首先，讓我分享一些在進入需求未被滿足的領域時觀察到的動態的一些見解。從識別符合條件的患者開始，在我們推出近一年後，我們看到人們對FR alpha 測試的整體意識有所提高，並且FOLR1 診斷的快速採用被納入對新診斷患者進行的初始小組的標準組成部分，以及患者進入下一線治療。

Our market research indicates that over 80% of physicians are familiar with FR alpha testing, up from a baseline of under 50% at the time of approval. It is becoming the standard of care that will enable oncologists to rapidly incorporate ELAHERE into their treatment decision, needless to say, testing has not been a barrier to adoption.

我們的市場研究表明，超過 80% 的醫生熟悉 FR alpha 測試，而批准時的基線不足 50%。它正在成為一種護理標準，使腫瘤學家能夠迅速將 ELAHERE 納入他們的治療決策中，不用說，測試並不是採用的障礙。

Since launch, we have endeavored to provide the market with a number of tests conducted at our 3 largest centralized labs. As of the end of the quarter, that number stood at roughly 16,000 tests. However, with approximately 40 labs now certified to run the tests, our visibility into the number of tests performed has decreased and will discontinue reporting on this metrics on subsequent calls. We will, however, continue to report the folate receptor alpha positive rate which remains between 35% and 40%, in line with our expectations.

自推出以來，我們一直致力於為市場提供在我們 3 個最大的集中實驗室進行的多項測試。截至本季末，該數字約為 16,000 次測試。然而，由於現在大約有 40 個實驗室獲得了運行測試的認證，我們對所執行測試數量的可見性有所下降，並且將停止在後續電話中報告此指標。然而，我們將繼續報告葉酸受體α陽性率仍維持在35%至40%之間，符合我們的預期。

Looking at patient adoption. ELAHERE addresses a high unmet need among platinum-resistant ovarian cancer patients. As indicated by the initial strong uptake in later life where the need has been great. In the first quarter, the vast majority of patients were from later lines of therapy. And as the launch has progressed, will shift to earlier lines. This is slow and steady trend, and we expect this to become a key driver of future growth.

正在考慮患者收養。 ELAHERE 解決了鉑類抗藥性卵巢癌患者未滿足的高度需求。正如後來生活中最初的強烈吸收所表明的那樣，那裡的需求很大。在第一季度，絕大多數患者都接受過較晚的治療。隨著發布的進展，將轉向早期的產品線。這是緩慢而穩定的趨勢，我們預計這將成為未來成長的關鍵驅動力。

Moving to our second key factor, access and reimbursement. Driven by the effort of our access team, we secured coverage policies aligned to our level for over 95% of both Medicare and commercial lives within the first 7 months of launch, exceeding another benchmark ADCs. In addition, with the inclusion of ELAHERE NCCN guidelines, we have seen utilization in a broad population, including the use of monotherapy related lines and in combination with bevacizumab in low, medium and high FR alpha presentations. Third, a strong execution by our commercial team driving adoption of ELAHERE. Our customer-facing team have been highly active since launch. During the third quarter, they continues to engage priority targets to broaden our reach resulting in continued growth in both academic and community accounts.

轉向我們的第二個關鍵因素，訪問和報銷。在我們的准入團隊努力的推動下，我們在推出後的前 7 個月內為超過 95% 的醫療保險和商業生活確保了符合我們水平的承保政策，超過了另一個基準 ADC。此外，隨著 ELAHERE NCCN 指南的納入，我們已經看到在廣泛人群中的使用，包括使用單一療法相關系列以及在低、中和高 FR α 表現中與貝伐單抗聯合使用。第三，我們商業團隊的強大執行力推動了 ELAHERE 的採用。自推出以來，我們面向客戶的團隊一直非常活躍。在第三季度，他們繼續致力於優先目標，以擴大我們的影響範圍，從而導致學術和社區帳戶的持續成長。

Complementing new account generation is a significant percentage of accounts with repeat orders. While academic institutions continue to comprise our largest customers, roughly 70% awarded during the quarter came from nonacademic institutions and community-based oncology groups, consistent with the prior quarter. And lastly, increased physician experience and awareness. We place a high priority on increasing awareness and cultivating a positive physician and patient experience. Based on our market research, in August we over 120 physicians across the academic and community setting, over 80% of physicians are aware of ELAHERE. This has nearly doubled since April, and we are especially pleased to see awareness increasing with medical oncology.

大量重複訂單的帳戶是新帳戶產生的補充。雖然學術機構仍然是我們最大的客戶，但本季約 70% 的授予來自非學術機構和社區腫瘤學團體，與上一季一致。最後，增加了醫生的經驗和意識。我們高度重視提高意識並培養積極的醫生和患者體驗。根據我們的市場調查，8 月我們對學術界和社區環境中的 120 多名醫生進行了調查，其中超過 80% 的醫生了解 ELAHERE。自四月以來，這一數字幾乎翻了一番，我們特別高興地看到腫瘤內科的認識不斷提高。

We attribute this to the compelling data from MIRASOL and to the robust engagement by our medical affairs team, who has continued to provide a full suite of support to ensure positive physician and patient experience. As a testament to their efforts, reports from the field consistently relate enthusiastic feedback from clinicians regarding their experience with ELAHERE.

我們將此歸功於 MIRASOL 令人信服的數據以及我們的醫療事務團隊的積極參與，他們持續提供全套支持，以確保積極的醫生和患者體驗。作為他們努力的證明，來自現場的報告一致反映了臨床醫生對 ELAHERE 體驗的熱情回饋。

In summary, we are very pleased with our performance to date. And based on the market research, I just referenced, we expect continuous growth due primarily by number one, increasing FR alpha testing. Awareness of FR alpha testing as a biomarker is already high, and physicians indicate a 30% growth with the convenience of an in-house testing and testing earlier in the patient journey. Two, increasing awareness of the benefits ELAHERE brings to patients with advanced ovarian cancer. As physicians gain experience and our medical affairs team continues to educate on our clinical data in both monotherapy and in combination, our research shows that physician education translates into increased depth and breadth of prescribing with current prescribers projecting higher rates of utilization in both monotherapy and combination. Also, we anticipate physicians previously unaware becoming new adopters.

總而言之，我們對迄今為止的表現非常滿意。根據我剛才提到的市場研究，我們預計持續成長主要歸功於第一，增加 FR alpha 測試。人們對 FR α 測試作為生物標記的認識已經很高，醫生表示，由於內部測試和患者早期測試的便利性，這一數字增長了 30%。第二，提高人們對 ELAHERE 為晚期卵巢癌患者帶來的益處的認識。隨著醫生經驗的累積以及我們的醫療事務團隊繼續對單一療法和聯合療法的臨床數據進行教育，我們的研究表明，醫師教育轉化為處方深度和廣度的增加，目前的處方者預計單一療法和聯合療法的利用率更高。此外，我們預計以前不知道的醫生會成為新的採用者。

Third, we also expect to see increase in premium rates over historical benchmarks given the compelling efficacy of ELAHERE and increased experience with the treatment, including the management of adverse events. Fourth, lines of therapy. Improving perceptions relative to the standard of care will support moving into earlier lines of therapeutic treatment in the platinum-resistant setting. Finally, we are also currently fielding a demand study, and we expect to gain additional insight into the current and future utilization of ELAHERE.

第三，鑑於 ELAHERE 令人信服的療效以及治療經驗的增加（包括不良事件的管理），我們也預期保費率將高於歷史基準。第四，線路治療。改善對護理標準的認識將支持在鉑類抗藥性環境中進入早期治療方案。最後，我們目前正在進行一項需求研究，我們希望對 ELAHERE 目前和未來的使用情況有更多的了解。

With that, I would like to turn the call over to Mike to provide additional color on the ELAHERE development program and our broader pipeline. Mike?

說到這裡，我想將電話轉給 Mike，為 ELAHERE 開發計劃和我們更廣泛的管道提供更多資訊。麥克風？

Thanks, Isabel. We were pleased to present additional data from MIRASOL, our randomized Phase III trial of ELAHERE in platinum-resistant ovarian cancer at the 24th Annual European Society of Gynecologic Oncology Congress in September. Dr. Van Gorp, Professor of Gynecologic/Oncology at the University of Leuven presented 2 subset analyses in an oral session, highlighting efficacy benefits with ELAHERE versus investigator choice or IC chemotherapy in progression-free survival, objective response rate and overall survival. Dr. Van Gorp reported on subsets defined by the number of prior lines of therapy or prior PARP inhibitor exposure. With no new safety signals arising from these analyses, these findings provide valuable insights for physicians and to ELAHERE's consistent clinical benefit compared to IC chemotherapy in both subsets.

謝謝，伊莎貝爾。我們很高興在 9 月舉行的第 24 屆歐洲婦科腫瘤學會年會上展示 MIRASOL 的更多數據，MIRASOL 是我們的 ELAHERE 治療鉑耐藥卵巢癌的隨機 III 期試驗。魯汶大學婦科/腫瘤學教授Van Gorp 博士在口頭會議中介紹了2 個子集分析，強調了ELAHERE 相對於研究者選擇或IC 化療在無進展生存期、客觀緩解率和總生存期方面的療效優勢。 Van Gorp 博士報告了先前治療線數或先前 PARP 抑制劑暴露定義的子集。由於這些分析沒有產生新的安全訊號，這些發現為醫生提供了寶貴的見解，並為 ELAHERE 與 IC 化療相比在兩個亞組中的一致臨床益處提供了寶貴的見解。

Turning now to the broader mirvetuximab clinical development program, we aim to expand the ELAHERE label into platinum-sensitive ovarian cancer and further position ELAHERE as the standard of care in fully receptor alpha-positive disease. We are currently advancing 3 sponsored clinical trials in support of these objectives.

現在轉向更廣泛的mirvetuximab臨床開發計劃，我們的目標是將ELAHERE標籤擴展到鉑敏感卵巢癌，並進一步將ELAHERE定位為完全受體α陽性疾病的護理標準。我們目前正在推進 3 項贊助的臨床試驗來支持這些目標。

Let's start with PICCOLO, our single-arm Phase II trial evaluating mirvetuximab monotherapy efficacy and safety in patients with FR alpha high platinum-sensitive ovarian cancer who have received at least 2 prior lines of platinum-containing therapy or have a documented platinum allergy. The unmet medical need in this patient population is noteworthy and growing, driven predominantly by 2 key factors. First, even if a patient meets the clinical criteria of platinum-sensitive disease, each subsequent line of platinum containing therapy is associated with both decreased efficacy as measured by a lower probability of achieving an objective response and meaningful response duration and decreased tolerability. But this reality, available therapy for these patients today is limited.

讓我們從PICCOLO 開始，這是我們的單臂II 期試驗，評估mirvetuximab 單藥治療對FR α 高鉑敏感卵巢癌患者的療效和安全性，這些患者之前至少接受過2 種含鉑治療或有鉑過敏記錄。該患者群體中未滿足的醫療需求值得注意且不斷增長，主要由兩個關鍵因素驅動。首先，即使患者符合鉑類敏感疾病的臨床標準，後續的每一種含鉑療法都與療效降低（透過實現客觀反應的機率較低和有意義的反應持續時間衡量）以及耐受性降低有關。但現實是，目前這些患者可用的治療方法是有限的。

Second, emerging clinical data indicate that treatment with a PARP inhibitor may negatively impact the efficacy of subsequent platinum containing therapy. Given the importance of PARP inhibitors in the maintenance setting in the first-line treatment regimen for many patients, the observations further reinforce the need for treatment alternatives. No randomized Phase III data exist for the patient population enrolled and treated in PICCOLO. No level one evidence, if you will. As such there is no agreed upon established standard of care for patients with later-line platinum-sensitive disease. Therefore, to design this trial, we synthesized historic data of both non-platinum monotherapy and platinum-containing regimens in similar patient populations. These analyses drove the trial to standard Simon two-stage design and its statistical assumptions. Regarding the former we defined objective response rate as the primary endpoint. The key secondary endpoint was (inaudible) duration of response. Safety and tolerability were important additional study objectives.

其次，新出現的臨床數據表明，PARP 抑制劑治療可能會對後續含鉑療法的療效產生負面影響。鑑於 PARP 抑制劑在許多患者第一線治療方案的維持環境中的重要性，這些觀察結果進一步強化了對治療替代方案的需求。尚無 PICCOLO 入組和治療患者群體的隨機 III 期數據。如果你願意的話，沒有一級證據。因此，對於晚期鉑類敏感疾病患者，目前尚無商定的既定照護標準。因此，為了設計這項試驗，我們綜合了類似患者族群中非鉑類單一療法和含鉑療法的歷史數據。這些分析促使試驗採用標準西蒙兩階段設計及其統計假設。對於前者，我們將客觀緩解率定義為主要終點。關鍵的次要終點是（聽不清楚）反應持續時間。安全性和耐受性是重要的額外研究目標。

Based upon the assumed or hypothesized objective response rate, we established the trial size to rule out a confirmed objective response rate by investigators of 28%. Because an observed objective response rate exceeding 28%, would set these data apart from the historic benchmark data I referenced above. In other words, and positive trial results would require an observed or actual objective response rate that excluded 28% based upon 95% confidence intervals. In the fully enrolled PICCOLO trial, a total of 79 patients have been treated, most of whom have received prior PARP inhibitor therapy. As of today, a number of those patients remain on treatment, continuing to receive mirvetuximab. Based upon the prespecified trial design until the response duration for the entire study population is mature, the trial remains ongoing. However, we are able to share today that based on an interim assessment of response and safety, the primary end point of the study has been achieved. The investigator-assessed objective response rate excludes 28%, and we anticipate an overall objective response rate of at least 48% when we report the full data in 2024.

根據假定或假定的客觀緩解率，我們確定了試驗規模，以排除研究人員確認的 28% 的客觀緩解率。因為觀察到的客觀回應率超過 28%，這些數據將與我上面引用的歷史基準數據區分開來。換句話說，積極的試驗結果需要觀察到的或實際的客觀反應率，根據 95% 置信區間排除 28%。在完全入組的 PICCOLO 試驗中，共有 79 名患者接受了治療，其中大多數人之前接受過 PARP 抑制劑治療。截至今天，其中一些患者仍在接受治療，並繼續接受米維妥昔單抗治療。根據預先指定的試驗設計，直到整個研究族群的反應持續時間成熟為止，試驗仍將持續進行。然而，我們今天可以分享的是，根據對反應和安全性的中期評估，研究的主要終點已經實現。研究者評估的客觀緩解率排除了 28%，我們預期當我們在 2024 年報告完整數據時，整體客觀緩解率至少為 48%。

Also of note, to date, we have detected no new safety signal bevacizumab. The insights I've shared today from the ongoing PICCOLO trial are meaningful as the numerically largest data set for mirvetuximab reported thus far in patients with platinum-sensitive disease, we believe these data reinforce earlier previously published data sets of mirvetuximab in combination that demonstrate mirvetuximab's potential in FR-alpha expressing platinum-sensitive ovarian cancer or PSOC. Assuming the tolerability and safety profile in PSOC that remains consistent with that observed across the mirvetuximab development program, we've seen mirvetuximab eventually becoming a new standard of care in PSOC assuming a trajectory similar to that already underway in platinum-resistant disease.

另外值得注意的是，迄今為止，我們尚未檢測到貝伐珠單抗的新安全訊號。我今天從正在進行的PICCOLO 試驗中分享的見解是有意義的，因為迄今為止在鉑類敏感疾病患者中報道的mirvetuximab 數據集最大，我們相信這些數據強化了先前發布的mirvetuximab 數據集，這些數據集證明了mirvetuximab 的在表達 FR-α 的鉑敏感卵巢癌或 PSOC 中具有潛力。假設PSOC 的耐受性和安全性與整個mirvetuximab 開發計劃中觀察到的情況保持一致，我們已經看到mirvetuximab 最終成為PSOC 的新護理標準，假設其軌跡類似於鉑類抗藥性疾病中已經發生的軌跡。

In addition to evaluating mirvetuximab monotherapy in PICCOLO, we are advancing 2 trials designed to establish mirvetuximab as the combination agent of choice in platinum-sensitive ovarian cancer. The first is GLORIOSA, our Phase III trial evaluating mirvetuximab plus bevacizumab maintenance versus standard of care, bevacizumab maintenance, in the second-line platinum-sensitive setting. This study builds upon our robust mirvetuximab plus bevacizumab data in the platinum-resistant setting, which led to the NCCN compendia listing for this combination. This combination in the maintenance setting is designed to establish the opportunity for patients to benefit from even longer durations of therapy with mirvetuximab.

除了評估 PICCOLO 中的 mirvetuximab 單藥療法外，我們還在推進兩項試驗，旨在將 mirvetuximab 確立為鉑敏感卵巢癌的首選聯合用藥。第一個是 GLORIOSA，我們的 III 期試驗在二線鉑敏感環境中評估了 mirvetuximab 加貝伐珠單抗維持治療與標準護理、貝伐珠單抗維持治療。這項研究建立在我們在鉑類抗藥性環境中可靠的米維妥昔單抗加貝伐珠單抗數據的基礎上，該數據導致該組合被列入 NCCN 藥典。這種維持治療組合的目的是讓患者有機會從更長的米維妥昔單抗治療中獲益。

The second is Trial 420, a single-arm Phase II study evaluating mirvetuximab plus carboplatin with mirvetuximab continuation until disease progression in platinum-sensitive ovarian cancer patients with low, medium or high levels of folate receptor alpha expression. Both GLORIOSA and Trial 420 are enrolling in the U.S. and advancing in Europe.

第二個試驗是試驗420，這是一項單組II 期研究，評估葉酸受體α 表達水平低、中或高的鉑敏感卵巢癌患者中米韋妥昔單抗聯合卡鉑以及持續使用米韋妥昔單抗直至疾病進展。 GLOROSA 和 Trial 420 均正在美國註冊並在歐洲推進。

Moving to our second pivotal program. We continue to anticipate top line data from the Phase II CADENZA trial of pivekimab sunirine or PVEK, in patients with frontline and relapsed/refractory blastic plasmacytoid dendritic cell neoplasm or BPDCN in 2024. Given the encouraging efficacy and tolerability data we have observed as presented at the European Hematology Association Annual Meeting earlier this year, we are excited about PVEK as a potential new option in this rare indication. In our AML program with PVEK, we continue to advance enrollment in our A02 trial of PVEK in combination with venetoclax and azacitidine which we refer to as the PVEK triplet. We expect to report data from this study at ASH in December. Two cohorts enrolled patients with newly diagnosed acute myeloid leukemia and each were designed to inform the optimal schedule of venetoclax in the PVEK triplet, a critical first step to guide further clinical development, including planned pivotal development in frontline AML.

轉向我們的第二個關鍵計劃。我們繼續預期2024 年pivekimab sunirine 或PVEK 在第一線和復發/難治性母細胞性漿細胞樣樹突細胞腫瘤或BPDCN 患者中進行的II 期CADENZA 試驗的主要數據。鑑於我們觀察到的令人鼓舞的療效和耐受性數據，如在今年早些時候的歐洲血液學協會年會上，我們對 PVEK 作為這一罕見適應症的潛在新選擇感到興奮。在我們與 PVEK 的 AML 專案中，我們繼續推進 PVEK 聯合維奈托克和阿扎胞苷的 A02 試驗的入組，我們將其稱為 PVEK 三聯體。我們預計 12 月在 ASH 上報告這項研究的數據。兩個隊列招募了新診斷的急性髓性白血病患者，每個隊列都旨在告知PVEK 三聯體中維奈托克的最佳用藥方案，這是指導進一步臨床開發的關鍵的第一步，包括計劃在一線AML 中進行關鍵開發。

As for our earlier stage programs, on IMGC936, our first-in-class ADAM9-targeting ADC in co-development with MacroGenics, we continue to progress our non-small cell lung cancer expansion cohort, and we plan to provide an update after the protocol specified interim analysis is completed, which we now expect to next year. Lastly, we are progressing our Phase I trial of IMGN151, our next-generation antifolate receptor alpha targeting ADC, to address a broader range of folate receptor alpha-expressing tumors. Initial exploration is in ovarian and endometrial cancers and dose escalation is proceeding as anticipated.

至於我們的早期項目，在 IMGC936（我們與 MacroGenics 共同開發的一流 ADAM9 靶向 ADC）上，我們繼續推進我們的非小細胞肺癌擴展隊列，我們計劃在協議規定的中期分析已完成，我們現在預計明年完成。最後，我們正在推進 IMGN151（我們的下一代抗葉酸受體 α 靶向 ADC）的 I 期試驗，以解決更廣泛的葉酸受體 α 表達腫瘤。初步探索是針對卵巢癌和子宮內膜癌，並且劑量遞增正在按預期進行。

With that, I will turn the call over to Lauren to cover our financials. Lauren?

這樣，我會將電話轉給勞倫，詢問我們的財務狀況。勞倫？

Thanks, Mike. For the third quarter of 2023, we generated $113.4 million in revenue, including $105.2 million in net product sales of ELAHERE, with the remainder primarily from noncash royalty revenues. Operating expenses were $85.3 million, comprised of $47.6 million of R&D expenses and $37.7 million of SG&A expenses. We recorded net income of $30.7 million and EPS of $0.10. We ended the quarter with $605.5 million in cash on the balance sheet.

謝謝，麥克。 2023 年第三季度，我們實現了 1.134 億美元的收入，其中 ELAHERE 的產品淨銷售額為 1.052 億美元，其餘部分主要來自非現金特許權使用費收入。營運費用為 8,530 萬美元，其中包括 4,760 萬美元的研發費用和 3,770 萬美元的銷售、一般管理費用。我們的淨利潤為 3,070 萬美元，每股收益為 0.10 美元。本季末，我們的資產負債表上有 6.055 億美元現金。

Our financial guidance for 2023 remains unchanged. We continue to expect revenues, excluding ELAHERE sales, between $45 million and $50 million and operating expenses between $350 million and $365 million. Lastly, since we are quickly approaching the end of 2023, I'd like to share that we anticipate providing full year ELAHERE revenue guidance for 2024 when we announce fourth quarter and full year 2023 financial results.

我們對 2023 年的財務指導保持不變。我們仍預期收入（不包括 ELAHERE 銷售額）在 4,500 萬至 5,000 萬美元之間，營運費用在 3.5 億至 3.65 億美元之間。最後，由於我們很快就要到 2023 年年底了，我想告訴大家，當我們宣布 2023 年第四季度和全年財務業績時，我們預計將提供 2024 年全年 ELAHERE 收入指引。

With that, we'll open the call for questions.

至此，我們將開始提問。

(Operator Instructions) And our first question coming from the line of John Newman with Canaccord.

（操作員說明）我們的第一個問題來自 Canaccord 的 John Newman。

Great continued work, successful launch. Just had two questions. On ELAHERE, I'm curious, if you're seeing ELAHERE use in combination with Avastin continue to grow as a share of total ELAHERE use? And also if you are expecting to see increased duration of therapy here? And then second, just a quick question on what we should be looking for in terms of the pivekimab data at ASH this year?

偉大的持續工作，成功啟動。只是有兩個問題。關於 ELAHERE，我很好奇，您是否看到 ELAHERE 與阿瓦斯汀聯合使用在 ELAHERE 總使用量中所佔的份額繼續增長？另外，您是否期望在這裡看到治療持續時間延長？其次，我想問今年 ASH 上的 pivekimab 數據我們應該尋找什麼？

I'll ask Isabel to answer those questions?

我會請伊莎貝爾回答這些問題嗎？

John, yes, well, we continue -- we are very pleased with the performance in the third quarter, as we said, over $100 million in sales. We continue to drive the utilization both in monotherapy in combination. While we have preliminary data on that, we could say, yes, there is growth involved, and we continue to see that, and our market research indicates that, that will continue to grow in the next few months. Can you please repeat your question on PVEK?

約翰，是的，我們繼續——我們對第三季的業績非常滿意，正如我們所說，銷售額超過 1 億美元。我們繼續推動單一療法的聯合應用。雖然我們有這方面的初步數據，但我們可以說，是的，確實存在成長，而且我們繼續看到這一點，而且我們的市場研究表明，未來幾個月將繼續成長。您能重複一下關於 PVEK 的問題嗎？

John, it's Mike. Yes, with respect to our upcoming data at ASH, as I mentioned in the prepared comments, we're going to have as much data as we -- essentially, as we have on the 2 cohorts that have solidified the dose and schedule of the triplet as we move forward in 802. So efficacy data, safety data, obviously, it's an ongoing study. And so sort of the maturation of those data with respect to response duration is something that's going to take more time. But I think we'll be able to expand a fair bit on what I just shared.

約翰，是麥克。是的，關於我們在ASH 上即將發布的數據，正如我在準備好的評論中提到的，我們將擁有盡可能多的數據——本質上，就像我們在2 個隊列中獲得的數據一樣多，這些數據已經鞏固了劑量和時間表隨著我們在 802 中前進，三重奏。因此，功效數據、安全數據，顯然，這是一項正在進行的研究。因此，這些數據相對於響應持續時間的成熟需要更多時間。但我認為我們將能夠對我剛剛分享的內容進行相當多的擴展。

Our next question coming from the line of Michael Schmidt with Guggenheim.

我們的下一個問題來自邁克爾·施密特與古根漢的合作。

Congrats on reaching cash flow positivity this quarter. Amazing job on the launch so far. Mark, or Isabel, could you comment a bit more what you think your treatment share is at this point in time in the platinum-resistant ovarian cancer setting as opposed to other patient subsets in this market? It's been a very strong launch, obviously. And then secondly, could you comment on how the PICCOLO trial result potentially reads through to other trials you have ongoing in platinum-sensitive ovarian cancer setting?

恭喜本季實現正現金流。到目前為止，發布的工作非常出色。 Mark 或 Isabel，您能多評論一下您認為目前在鉑類抗藥性卵巢癌治療中相對於該市場中其他患者亞群的治療份額嗎？顯然，這是一次非常強勁的發布。其次，您能否評論一下 PICCOLO 試驗結果如何影響您在鉑敏感卵巢癌環境中正在進行的其他試驗？

Mike, I'll start and then ask Isabel and Mike to address the additional points here. So we aren't in a position to quote you a specific share at this point. The way we are looking at the business is we see some important trends. I think we've characterized this slow but steady growth as we look at the utilization of the product as monotherapy. So when we started out, the majority of the patients were fourth and later line as time has gone by what we see in the claims data is movement into earlier lines of therapy. And in parallel with that, we see combination use of the products growing as well. And so -- but to sort of stand back at this point and give you a specific share number, just not in a position to do that. Isabel, I don't know if you want to add anything to that? .

麥克，我將首先請伊莎貝爾和麥克解決這裡的其他問題。因此，我們目前無法向您提供具體份額的報價。我們看待業務的方式是看到一些重要的趨勢。我認為，當我們將該產品用作單一療法時，我們已經描述了這種緩慢但穩定的增長。因此，當我們開始時，大多數患者都處於第四線及之後的一線治療，隨著時間的流逝，我們在索賠數據中看到，正在進入早期的治療線。同時，我們看到產品的組合使用也在成長。所以，但此時退後一步，給你一個具體的股數，就是無法做到這一點。伊莎貝爾，我不知道你是否想補充什麼？ 。

No, I just would like to say that this is an area of high unmet need and what we are pleased is to see a steady adoption across all the accounts, and significant depth and breadth in both academic and community savings. So we expect this will continue to increase in terms of market share, we are not in a position to comment at this time.

不，我只是想說，這是一個需求未被滿足的領域，我們很高興看到所有帳戶的穩定採用，以及學術和社區儲蓄的顯著深度和廣度。因此，我們預計市場份額將繼續增加，目前我們無法發表評論。

Thanks, Mike, for the question. In terms of the PICCOLO data. I can't imagine a better foundation on which to build in platinum-sensitive ovarian cancer than interim assessment that we've been able to share with respect to PICCOLO. This is a -- just to remind you, this is a heavily pretreated population of patients with platinum-sensitive disease. And when we look across the available therapy, which is very heterogeneous because there are so few options. We see single-agent monotherapy, objective response rates in the high single digits to low double digits, and we see a platinum-based doublet objective response rates anywhere between the high 20s and high 30s. And here we are with an interim assessment of an ongoing study where we expect at least 48% objective response rate. So this sets a really nice foundation for the continued work of mirvetuximab in platinum-sensitive disease.

謝謝邁克提出這個問題。就 PICCOLO 數據而言。我無法想像比我們就 PICCOLO 分享的中期評估更好的基礎來建立鉑敏感卵巢癌的基礎。這是一個——只是提醒您，這是一個經過大量預先治療的患有鉑敏感疾病的患者群體。當我們審視現有的治療方法時，會發現這些治療方法非常多樣化，因為選擇太少了。我們看到單藥單一療法的客觀緩解率在高個位數到低兩位數之間，我們看到基於鉑類的雙藥客觀緩解率在 20 多歲到 30 多歲之間。我們對一項正在進行的研究進行了中期評估，預計客觀反應率至少為 48%。因此，這為米維妥昔單抗在鉑類敏感疾病的持續研究奠定了良好的基礎。

And our next question coming from the line of Etzer Darout with BMO Capital Markets.

我們的下一個問題來自 BMO 資本市場的 Etzer Darout。

Congrats on continued ELAHERE execution here. Maybe on PICCOLO, and thanks for the additional color on the study. Just wanted to know if you could comment at all on sort of the standard of care, duration of response and sort of just sort of level-setting expectations from sort of a standard of care perspective for that study? And I had a question on ADAM9 as well. Just thinking about sort of some of the recent data we got at ESMO from the TROP2 mechanism. In terms of the response dynamics potentially and sort of a squamous versus non-squamous non-small cell cancer population, if you could comment at all on sort of the ADAM9 mechanism and whether or not there's sort of a preference or first preference for a particular sort of non-squamous histology.

恭喜 ELAHERE 在這裡繼續執行。也許在 PICCOLO 上，感謝您為研究提供了額外的色彩。只是想知道您是否可以從該研究的護理標準角度對護理標準、反應持續時間以及設定水平的期望發表評論？我也有一個關於 ADAM9 的問題。想想我們最近在 ESMO 從 TROP2 機制獲得的一些數據。就潛在的反應動態以及鱗狀細胞癌與非鱗狀細胞非小細胞癌群體的排序而言，您是否可以評論一下 ADAM9 機制以及是否對特定的偏好或第一偏好一種非鱗狀組織學。

Sure. This is Mike. Let me respond to the second question first. I think the long and the short of it is that ADAM9 is broadly expressed and we look forward if there's any -- if there's any signal that we see that is distinguishable based on histology, when we have that expansion data, we'll obviously be looking forward to sharing that. But at this point, given the broad expression across epithelial cancers, we're continuing to look broadly in that cohort. .

當然。這是麥克。我先回答第二個問題。我認為總而言之，ADAM9 被廣泛表達，我們期待是否有任何信號 - 如果我們看到任何信號可以根據組織學進行區分，當我們擁有擴展數據時，我們顯然會期待分享。但目前，鑑於上皮癌的廣泛表達，我們將繼續在該族群中進行廣泛的研究。 。

With respect to the first question, I just want to reinforce that we're really looking forward next year, sharing the full data from PICCOLO. And it's -- your questions are really going to be relevant in the context of the specific demographics, even more detail than what we're able to share today with respect to, for example, more detail around the platinum-free interval in this patient population to be able to better interpret not just the interim assessment objective response rate that we're seeing, but also the durability of response and other factors that are going to be important to essentially round out this interim assessment with the full data. So we're really looking forward to that. And like I said, I think we've shared that we expect that in next year.

關於第一個問題，我只想強調，我們非常期待明年分享 PICCOLO 的完整數據。您的問題確實與特定人口統計背景相關，甚至比我們今天能夠分享的內容更詳細，例如，有關該患者無鉑間隔的更多詳細信息人口不僅能夠更好地解釋我們所看到的中期評估客觀反應率，而且能夠更好地解釋反應的持久性和其他因素，這些因素對於利用完整數據基本上完善中期評估非常重要。所以我們真的很期待這一點。就像我說的，我想我們已經分享了我們對明年的期望。

Next question our next question coming from the line of Boris Peaker with TD Cowen.

下一個問題 我們的下一個問題來自 Boris Peaker 和 TD Cowen 的對話。

Congratulations on the progress. Two questions for me. So first, on ELAHERE, I'm just curious what is the current duration of therapy? And how do you expect, I guess, to increase in PICCOLO patients? And the second is maybe kind of get your general thoughts on the competitive products, DS-6000 from Daiichi that's in early stage development?

祝賀取得的進展。有兩個問題問我。首先，在 ELAHERE 上，我只是好奇目前的治療時間是多久？我想，您預計 PICCOLO 患者的數量會如何增加？第二個可能是您對處於早期開發階段的競爭產品 DS-6000 的整體看法？

Yes. Boris, the claims data that we have at this point are not sufficient to allow us to project duration of therapy among the patients that have been treated. As a general rule, what we observe is that patients in earlier lines tend to have higher response rates and stay on drug longer. We reserve that same phenomenon with the use in combination.

是的。鮑里斯，我們目前掌握的索賠數據不足以讓我們預測已接受治療的患者的治療持續時間。作為一般規則，我們觀察到，早期治療的患者往往有更高的緩解率，並且服藥時間更長。我們保留與組合使用相同的現象。

Boris, it's Mike. And with respect to your second question, Yes, clearly, the data you referenced that were presented, I think, last week are interesting. It's the Phase I experience. It looks to me, at least from the data, there's some work to do with respect to identifying the appropriate dose. It's going to be something that we're going to want to keep an eye on and think about ways in which those data progress, but we're years ahead in terms of the platinum-resistance space, and candidly, the platinum-sensitive space in terms of where we're at with ELAHERE.

鮑里斯，是麥克。關於你的第二個問題，是的，顯然，我認為你上週提到的數據很有趣。這是第一階段的經驗。在我看來，至少從數據來看，在確定適當的劑量方面還有一些工作要做。這將是我們想要密切關注並思考這些數據進展方式的事情，但我們在鉑電阻領域以及坦率地說，在鉑敏感領域方面領先了數年就我們與 ELAHERE 的情況而言。

Our next question coming from the line of Brian Cheng with JPMorgan.

我們的下一個問題來自摩根大通的 Brian Cheng。

Congrats on the quarter. Mark, how should we think about the sales trajectory next year from the dynamics of patients on combo with bev and the use in early line versus discontinuation just due to natural progression. How should we think about the trajectory moving forward? And then two on PICCOLO. How should we think about the regulatory path look like post your PICCOLO final analysis? And do you think the final analysis will give you a sufficient leverage for conversation for label expansion next year?

恭喜本季。馬克，我們應該如何從 Bev 聯合用藥患者的動態以及早期使用與僅僅由於自然進展而停藥的患者動態來考慮明年的銷售軌跡。我們該如何思考前進的軌跡？然後是 PICCOLO 上的兩個。在 PICCOLO 最終分析之後，我們應該如何考慮監管路徑？您認為最終的分析會為您帶來足夠的影響力來進行明年品牌擴張的對話嗎？

Thanks, Brian. I'll start. Look, we expect to see continued growth. We will give guidance in conjunction with our earnings call in February of next year when we report our full year results. But for the reasons that Isabel articulated in her opening comments. What we see from our market research is increased testing, and that trend should continue, increasing awareness. Right now, the survival data are not currently in the label and so we can't directly promote that information. With the submission of the SBLA and subsequent approval, we'll be able to go to the market with that. And what we observed from the market research at this point is with increased education, we also see increase the breadth and depth of prescribing both as it relates to the monotherapy as well as in combination. We think there are rising treatment rates. So this is a new therapy in an area of unmet need.

謝謝，布萊恩。我開始吧。看，我們預計會看到持續成長。我們將在明年 2 月報告全年業績時結合財報電話會議提供指導。但出於伊莎貝爾在開場白中闡述的原因。我們從市場研究中看到測試的增加，這種趨勢應該會持續下去，從而提高人們的意識。目前，生存數據尚未出現在標籤中，因此我們無法直接宣傳該資訊。隨著 SBLA 的提交和隨後的批准，我們將能夠將其推向市場。我們從目前的市場研究中觀察到，隨著教育程度的提高，我們也看到處方的廣度和深度都在增加，因為它與單一療法以及聯合療法有關。我們認為治療率正在上升。因此，這是一個未滿足需求領域的新療法。

We've pointed out earlier that this is the first drug approved specifically in ovarian cancer in almost the last decade. And so the expectation here is that treatment rates will increase. And then in particular, with the MIRASOL data, we have the ability to compare and contrast against the standard of care. And when we do that, what we observed again in the research is an inclination to use the drug earlier in the treatment cascade. And so we do anticipate these questions over the course of the call and today. And so -- what I would say again is that we do expect continued growth, but I think it's also fair to say that coming off of $100-plus million base, the slope of the curve will not be as steep as it was in the past couple of quarters.

我們之前已經指出，這是近十年來第一種專門用於治療卵巢癌的藥物。因此，這裡的預期是治療率將會增加。特別是，透過 MIRASOL 數據，我們能夠與護理標準進行比較和對比。當我們這樣做時，我們在研究中再次觀察到的是治療級聯的早期使用該藥物的傾向。因此，我們確實在電話會議和今天的過程中預料到了這些問題。因此，我要再說一遍的是，我們確實預計會持續成長，但我認為也可以公平地說，從 1 億多美元的基數來看，曲線的斜率不會像 2019 年那樣陡峭。過去幾個季度。

And this is Mike. Regarding -- yes. This is Mike. Regarding your -- yes, your second question. So first of all, let's just keep in mind where we're at, right? This is a foundational data that will unequivocally be clinically meaningful in this patient population. And the reason that the full data set won't be available until mid-2024 is because of the importance of presenting mature durability of response data. And just to keep in mind, the last patient was enrolled in this study early this year. So it gives you a sense of the importance of what that mature response durability data will be. I fully expect, given what we know today, that these data will support compendia listing eventually when we see the full data. And I'd like to reserve judgment on dialogue with regulatory authorities until we have that full data because there's just no way to put an overall objective response rate into context with that the durability of response.

這是麥克。關於——是的。這是麥克。關於你的——是的，你的第二個問題。首先，讓我們記住我們現在所處的位置，對吧？這是一個基礎數據，對於該患者群體具有明確的臨床意義。完整資料集要到 2024 年中期才能提供，是因為提供成熟的回應資料持久性非常重要。請記住，最後一位患者是在今年年初參加這項研究的。因此，它讓您了解成熟的響應耐久性資料的重要性。鑑於我們今天所了解的情況，我完全期望當我們看到完整的數據時，這些數據最終將支持概要清單。在我們獲得完整數據之前，我想保留對與監管機構對話的判斷，因為沒有辦法將整體客觀回應率與回應的持久性聯繫起來。

Our next question coming from the line of Alexandra Ramsey with William Blair.

我們的下一個問題來自亞歷珊卓·拉姆齊和威廉·布萊爾。

Congrats on all the progress this quarter. So two quick questions. I guess first on PICCOLO. That 48% response rate that you mentioned that you'll present -- potentially present with the full data. I just want to confirm that, that's a confirmed 48% response rate? And then, looking at the MIRASOL data presented earlier at ASCO, it appears that the PARP-treated patients actually responded better than the PARP-naive patients. So I was just wondering if you could provide some color on why that might be the case?

恭喜本季取得的所有進展。那麼兩個簡單的問題。我想首先是短笛。您提到您將呈現的 48% 回應率 - 可能會呈現完整的數據。我只是想確認一下，這就是確認的 48% 回覆率嗎？然後，查看先前在 ASCO 上提供的 MIRASOL 數據，似乎接受 PARP 治療的患者實際上比未接受 PARP 的患者反應更好。所以我只是想知道你是否可以提供一些解釋為什麼會發生這種情況？

Yes. So this is Mike. Regarding your second question, it's important in that subset analysis to look at the demographics of the patient population when the MIRASOL data set is parsed by prior exposure to PARP inhibitor or not. We tried to point that out in the presentation, and I'd encourage you to go back and look at that. But the long and short of it is, there are some differences that are more apparent in the PARP-naive population. And generally, in terms of outcomes, it's not surprising necessarily that we see slightly better outcomes in patients that are appropriate based on the molecular profiling for PARP inhibitors. .

是的。這就是麥克。關於第二個問題，在子集分析中，當 MIRASOL 資料集是否透過先前是否接觸 PARP 抑制劑進行解析時，查看患者群體的人口統計資料非常重要。我們試圖在演示中指出這一點，我鼓勵您回去看看這一點。但總而言之，在未接受過 PARP 的族群中存在一些更明顯的差異。一般來說，就結果而言，我們在基於 PARP 抑制劑的分子分析的適當患者中看到稍微更好的結果，這並不奇怪。 。

And with respect to the first question, yes, so this is an interim assessment. It was a planned interim assessment following full enrollment. And these data are confirmed. The one caveat I'll say, and I think Mark mentioned this as well, is that this is an ongoing trial, right, with patients -- a number of patients that are still receiving therapy. And so in the parlance of a clinical researcher, we confirm the data when we share something like this. But of course, we need to reserve the caveat that when the full data are presented mid next year that in the process of providing those full data, there could be minor shifts in the data, and that's why we're really clear to talk about an objective response rate of at least 48%.

關於第一個問題，是的，所以這是一個臨時評估。這是全面註冊後計劃進行的中期評估。而這些數據都得到了證實。我要說的一個警告是，我想馬克也提到了這一點，這是一項正在進行的試驗，對吧，針對的是患者——許多仍在接受治療的患者。因此，用臨床研究人員的話來說，當我們分享這樣的事情時，我們確認了數據。但當然，我們需要保留一個警告，即當明年年中提供完整數據時，在提供這些完整數據的過程中，數據可能會出現微小的變化，這就是為什麼我們非常清楚地談論客觀回應率至少為48%。

Okay. No, that makes sense. And so you are seeing kind of durability increase over time. It sounds like based on how long people have been on treatment but just confirming that.

好的。不，這是有道理的。所以你會看到耐久性隨著時間的推移而增加。這聽起來像是基於人們接受治療的時間，但只是證實了這一點。

Yes. I mean the issue of the maturity of the duration of response is exactly why we're providing some guidance today that we would expect the full data in 2024.

是的。我的意思是，回應持續時間的成熟度問題正是我們今天提供一些指導的原因，我們預計將在 2024 年獲得完整數據。

Our next question coming from the line of Peter Lawson with Barclays.

我們的下一個問題來自巴克萊銀行的彼得勞森。

Just going back to your comments around Daiichi's CDH6 ADC. Just curious on what you thought of the data and if kind of that response rate and durability kind of holds up kind of how you think physicians will make a pick between Daiichi's molecule and your molecule? And then on PICCOLO, if I could just go back to that. Does the 48% mean there's kind of unconfirms there and it should get to above 48% or are at 48%. So any details around that kind of any detailed commentary you made, would be great.

回到您對 Daiichi CDH6 ADC 的評論。只是好奇你對這些數據的看法，以及這種反應率和持久性是否能支持你認為醫生會如何在第一的分子和你的分子之間做出選擇？然後在 PICCOLO 上，如果我可以回到那個。 48% 是否意味著存在某種不確定性，它應該達到 48% 以上或處於 48%。因此，有關您所做的任何詳細評論的任何細節都會很棒。

Yes. Well, I'll say to the second point, which kind of relates to the prior question is that we do see late responses in our data sets generally. And as I mentioned, there are a number of patients that remain on mirvetuximab. So at this interim assessment, we can confidently say that we see an objective response rate of 48%, but we just need to be cognizant of those number of patients that remain on therapy. So could the objective response rate at the final day to be higher? Yes, it could be higher.

是的。好吧，我要說的是第二點，與前面的問題相關的是，我們通常會在資料集中看到較晚的回應。正如我所提到的，有許多患者仍在服用米維妥昔單抗。因此，在這次中期評估中，我們可以自信地說，我們看到的客觀緩解率為 48%，但我們只需要了解仍在接受治療的患者數量。那麼最後一天的客觀回覆率能不能更高一些呢？是的，它可能會更高。

With respect to your first question, it's so conjectural. I mean, like you said, we've got a Phase I molecule that has a really interesting early signal. Like I said earlier, looks like to me, we're trying to figure out dose that I think there were some grade 5 interstitial lung disease-related deaths. So gosh, I hope for patients that were able to work through that and it becomes potentially someday a meaningful therapy in ovarian cancer. But I think it's a little premature from where I sit to try to hypothesize about how physicians are going to make treatment choices compared to a medicine that has demonstrated survival benefit in platinum-resistant ovarian cancer.

關於你的第一個問題，這是非常推測的。我的意思是，就像你說的，我們已經有了一個具有非常有趣的早期訊號的第一階段分子。就像我之前說的，在我看來，我們正在試圖找出我認為存在一些與 5 級間質性肺病相關的死亡的劑量。所以天哪，我希望患者能夠克服這個問題，並且有一天它可能成為卵巢癌的一種有意義的療法。但我認為，與已證明對鉑類抗藥性的卵巢癌有生存益處的藥物相比，嘗試假設醫生將如何做出治療選擇還為時過早。

Perfect. Thanks for the additional detail. What's the overlap between FR alpha and CDH6?

完美的。感謝您提供更多詳細資訊。 FR alpha 和 CDH6 有什麼重疊？

Yes. We're looking hard to understand that. I can't give you any numbers today. But when we have a better understanding of that, of course, we'll be able to share that.

是的。我們很難理解這一點。今天我無法給你任何數字。但是，當我們對此有了更好的理解時，當然，我們就能夠分享這一點。

Our next question coming from the line of Kelly Shi with Jefferies.

我們的下一個問題來自凱莉·史（Kelly Shi）和杰弗里斯（Jefferies）的電話。

Congrats on another great quarter. I have two. Firstly, on the regulatory approval, would you be able to share your launch of strategy in Europe at the moment? And also, how should we consider the cost associated with the launch? And another question regarding the ADAM9 program. So for the upcoming update in non-small cell lung cancer, could you share what interim analysis? Is it based on is -- is it a response rate or the durability of response?

恭喜又一個偉大的季度。我有兩個。首先，關於監管審批，您能否分享一下您目前在歐洲推出的策略？另外，我們應該如何考慮與發布相關的成本？還有一個關於 ADAM9 程式的問題。那麼對於即將到來的非小細胞肺癌的更新，您能分享一下什麼中期分析嗎？它是基於回應率還是回應的持久性？

I'll just briefly respond to the second question, and I think Mark or Isabel may tackle your question about Europe. So this is a cohort expansion of a Phase I study. And so it's essentially -- think about it as sort of fully enrolling that cohort and having the sufficient data to be able to share that in totality. It's nothing really more complicated than that and if patients remain in the cohort, it's just prudent to -- on therapies it's prudent to wait for that to mature and we look forward to sharing those data next year.

我將簡單回答第二個問題，我認為馬克或伊莎貝爾可以回答你關於歐洲的問題。這是第一階段研究的隊列擴展。因此，本質上，可以將其視為完全註冊該群體並擁有足夠的數據以便能夠整體共享這些數據。沒有什麼比這更複雜的了，如果患者留在隊列中，謹慎的做法是——在治療方面，謹慎的做法是等待成熟，我們期待明年分享這些數據。

Great. And so in terms of Europe, I'll start and then ask Isabel to comment further. But we were very pleased to announce last week that the EMA had validated our marketing authorization application. And we think that sets us up very nicely for an approval late next year. In terms of the launch sequence, we're on the ground already in Europe with established headquarters in Switzerland and a small staff to support the key functions around market access, regulatory and the like and are starting to build a team to support initial sales in Germany, and then there'll be subsequent countries added on as we go forward. And then I'll let Isabel talk a little bit about the market. And overall, the comment here is that we can address this market with a modest incremental investment for the business. But maybe just talk a little bit about the dynamics there.

偉大的。因此，就歐洲而言，我將首先請伊莎貝爾進一步發表評論。但我們上週非常高興地宣布 EMA 已經驗證了我們的行銷授權申請。我們認為這為我們明年晚些時候獲得批准做好了很好的準備。就啟動順序而言，我們已經在歐洲落地，在瑞士設立了總部，並配備了少量員工來支持市場准入、監管等關鍵職能，並開始組建一個團隊來支持歐洲的初始銷售。德國，然後隨著我們的進展，還會增加後續國家。然後我會讓伊莎貝爾談談市場。總的來說，這裡的評論是，我們可以透過適度的增量投資來應對這個市場。但也許只是談談那裡的動態。

Yes, Mark, thank you. Well, as we have shared previously, the market in Europe is highly concentrated, and really the majority of the 65 centers account for about 80% of the patients there. So as Mark alluded to, with a small investment, we are able to reach these customers. We also have started already our engagement. And as you saw, we presented at ASCO and ESMO, and we have very strong relationships with KOLs in Europe that are really excited to have this therapy available to them and of course are very much supporting our efforts in this. In addition to that, we are building up our team in Swiss and Germany, in other countries, and we are very excited to start our market research, our preparations to basically replicate the success of the launch that we had seen in the U.S.

是的，馬克，謝謝你。那麼，正如我們之前所分享的，歐洲市場高度集中，實際上65個中心中的大多數佔據了那裡約80%的患者。因此，正如馬克所提到的，只需少量投資，我們就能夠接觸到這些客戶。我們也已經開始了我們的合作。正如您所看到的，我們在ASCO 和ESMO 上進行了展示，並且我們與歐洲的KOL 建立了非常牢固的關係，他們非常高興能夠為他們提供這種療法，當然也非常支持我們在這方面的努力。除此之外，我們正在瑞士和德國以及其他國家建立我們的團隊，我們非常高興開始我們的市場研究，我們的準備工作基本上複製了我們在美國看到的成功發布。

And one other point to add to that, which is Kelly, our physician base there has tremendous experience with the drug already. So when we look at MIRASOL, we look at SORAYA more than 70% of the patients were enrolled outside of the United States, and the vast majority of those were enrolled in Europe. And so this is a group of physicians that has already significant experience with the drug. So we're excited about our prospects there.

還有一點要補充的是，凱利，我們那裡的醫生基地已經擁有該藥物的豐富經驗。因此，當我們查看 MIRASOL 和 SORAYA 時，超過 70% 的患者在美國以外的地區入組，其中絕大多數在歐洲入組。因此，這是一群已經在該藥物方面擁有豐富經驗的醫生。因此，我們對那裡的前景感到興奮。

And our next question coming from the line of Asthika Goonewardene from Truist.

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

First off, congrats on another robust quarter for you guys especially coming in line with the aggressive buy side expectation. That's good to see. Totally understand that you can't be too specific on off-label use here, but can you at least give us some sort of a bit of color here on what off-label population is the largest in what you're seeing so far? And what is growing the most rapidly. I think that could just be a little helpful here for us as we're tweaking our models here.

首先，恭喜你們又一個強勁的季度，特別是符合積極的買方預期。很高興看到這一點。完全理解，您不能在這裡對標籤外使用過於具體，但是您至少可以給我們一些顏色，說明迄今為止您所看到的標籤外人群最多的情況嗎？以及成長最快的是什麼。我認為這對我們來說可能有點幫助，因為我們在這裡調整我們的模型。

And then on PICCOLO, good to hear about what the ORR is trending at, but what about duration of response? As you've given us what the statistical bars for ORR, can you tell us what you need to beat for DOR? And I'll also add in previous calls, I think Anna and some of you guys have mentioned that suggested that this could be also an area where PICCOLO could look good. So I just want to see if you feel confident about that as well now that you're seeing more of the data in-house? And then lastly, do you need to publicly present PICCOLO in order to discuss it with the NCCN? Or can you share that with the NCCN ahead of a public presentation?

然後在 PICCOLO 上，很高興聽到 ORR 的趨勢，但是響應持續時間呢？既然您已經向我們提供了 ORR 的統計標準，您能告訴我們您需要擊敗 DOR 嗎？我還要在之前的電話中補充一下，我認為 Anna 和你們中的一些人已經提到，這也可能是 PICCOLO 看起來不錯的一個領域。所以我只是想看看，既然您看到了更多的內部數據，您是否對此也有信心？最後，您是否需要公開展示 PICCOLO 才能與 NCCN 進行討論？或者您可以在公開演講之前與 NCCN 分享這一點嗎？

So let me start with the market question. And you can talk about PICCOLO and NCCN. So in terms of discretionary use of this product outside the label, the first thing to keep in mind is that our label is platinum-resistant ovarian cancer in patients who've received 1 to 3 prior lines of therapy who are FR alpha positive. So what we observed very early on was that consistent with the NCCN guidelines that physicians were using the product in later line patients. So beyond a patient who had 3 prior therapies, and that continues as we speak. We then observed that there are patients who might not be -- might not qualify as FR alpha high who nonetheless are getting therapy as monotherapy, where the FR alpha expression is close to what would be considered FR alpha high.

讓我從市場問題開始。您還可以談論 PICCOLO 和 NCCN。因此，就在標籤外酌情使用該產品而言，首先要記住的是，我們的標籤適用於已接受過 1 至 3 種既往治療且 FR α 陽性的患者的鉑耐藥性卵巢癌。因此，我們很早就觀察到，醫生在後期患者中使用該產品與 NCCN 指南一致。因此，除了接受過 3 次先前治療的患者之外，這種情況在我們說話時仍在繼續。然後我們觀察到，有些患者可能不符合 FR α 高水平，但仍在接受單一療法，其中 FR α 表達接近被認為是 FR α 高的水平。

Just as a reminder to folks, FR alpha high is defined as 75% of the patient's tumor sample expressing FR alpha at 2-plus intensity staining. And so when a pathology report comes back from our labs, it has 2 readouts. One is positive or negative based on whether it meets that cut point of 75% at 2-plus intensity staining. But also, there's a numerical score with respect to the expression level. So it's stated in 5 percentage point increments, so 75, 80, 85, up to 100 and then downwards for 70, 65 and so on. What we hear anecdotally through market research in our advisory boards is that many physicians with a 70% reading will initiate monotherapy. As the FR alpha expression levels go down, there's the opportunity to engage around combination use.

提醒人們，FR α 高被定義為患者腫瘤樣本中 75% 在 2 以上強度染色時表達 FR α。因此，當我們實驗室返回病理報告時，它有 2 個讀數。一種是陽性還是陰性取決於它是否滿足 2+ 強度染色時 75% 的臨界點。而且，還有一個關於表達水平的數字分數。因此，它以 5 個百分點的增量表示，即 75、80、85，最高為 100，然後向下為 70、65，依此類推。我們透過諮詢委員會的市場研究得知，許多擁有 70% 閱讀率的醫生將開始單一療法。隨著 FR α 表現量下降，就有機會參與組合使用。

And again, the NCCN guidelines are supportive here where they include use of the product for patients with medium and low levels of expression. And so we -- as I said, we see use in later lines. It's a little hard to -- we can't sort of match a patient who had a 70% level of expression with monotherapy use at this point, the data -- we're not able to from a data perspective to match those 2 things. And then we do see an increasing use of combination and it comes through most prominently in our market research relative to the claims data, which lag a little bit. And I think a number of you on the call have produced your own sort of market research studies that show both existing and anticipated increasing use of combination therapy. I don't know if you want to add anything to that?

NCCN 指南再次提供了支持，其中包括將該產品用於中度和低度表達的患者。因此，正如我所說，我們在後面的線路中看到了使用。這是有點困難 - 我們無法將表達水平為 70% 的患者與單一療法的使用在這一點上進行匹配，數據 - 我們無法從數據的角度來匹配這兩件事。然後我們確實看到組合的使用越來越多，並且它在我們的市場研究中相對於索賠數據最為突出，而索賠數據有點滯後。我認為在座的一些人已經進行了自己的市場研究，顯示了現有的和預期的聯合療法的增加使用。不知道你是否還想補充什麼？

Yes. I just want to say awareness of NCCN guidelines has increased and it has been included in some of the pathways to some of the centers. And NCCN guidelines has guidelines around high, medium to low on monotherapy in addition to lifting the value of the combination. So in addition to being used in later lines of therapy, yes, we see use on mediums and lows, particularly in combination.

是的。我只想說，人們對 NCCN 指南的認識有所提高，並且它已包含在通往某些中心的一些途徑中。 NCCN 指南除了提高聯合治療的價值外，還針對單藥治療的高、中、低水平制定了指南。因此，除了用於後期治療之外，是的，我們還看到了中度和低度治療的使用，特別是聯合使用。

And this is Mike. With respect to your second, third and fourth questions. Let me make a point about this patient population that perhaps haven't been quite explicit enough about. But when a patient with natural history, who has still platinum-sensitive disease in third or subsequent lines, there's an important dichotomization around the relative platinum sensitivity that a clinician is thinking about when they think about appropriate therapy at this stage. And that's important as we think about the full data when we see those data next year because the durability of response, just like the objective response rate are going to be influenced whether the patient population has a platinum-free interval that's relatively short versus a platinum-free interval that's relatively long. .

這是麥克。關於你的第二、第三、第四個問題。讓我對這個患者群體提出一個可能不夠明確的觀點。但是，當具有自然病史的患者在三線或後續線中仍患有鉑類敏感疾病時，臨床醫生在現階段考慮適當的治療時會考慮相對鉑類敏感性的重要二分法。這很重要，因為當我們明年看到這些數據時，我們會考慮完整的數據，因為反應的持久性，就像客觀反應率一樣，是否會影響患者群體的無鉑治療間隔是否相對較短，而不是鉑類治療- 免費間隔時間相對較長。 。

And you can imagine or hypothesize that if the clinician is even considering a monotherapy non-platinum agent in the clinical trial like mirvetuximab that when we see the final data, I would expect that we'd have a substantial proportion of patients that have a short -- relatively short platinum-free interval. And that's really important to help interpret the full data set, along with the proportion of patients that have prior exposure to PARP inhibitors and bevacizumab. So it's all of those clinical factors and demographics that needs to be incorporated into the interpretation of the data to be able to put the data into context with respect to the objective response rate and durability of response.

您可以想像或假設，如果臨床醫生甚至在臨床試驗中考慮使用米維妥昔單抗等單一療法非鉑類藥物，那麼當我們看到最終數據時，我預計我們會有相當大比例的患者出現短期症狀。— 無鉑間隔相對較短。這對於幫助解釋完整的資料集以及先前接觸過 PARP 抑制劑和貝伐珠單抗的患者比例非常重要。因此，所有這些臨床因素和人口統計數據都需要納入數據解釋中，以便能夠將數據置於客觀緩解率和緩解持久性方面。

And with respect to your question around NCCN, I think a working assumption should be that the NCCN is looking for published data sets to review in the context of updating their guidelines.

關於您關於 NCCN 的問題，我認為一個可行的假設應該是 NCCN 正在尋找已發布的資料集，以便在更新其指南的背景下進行審查。

We have time for 1 more question.

我們還有時間回答 1 個問題。

Certainly. Our last question coming from the line of Li Chen with H.C. Wainwright.

當然。我們的最後一個問題來自 Li Chen 和 H.C.溫賴特。

This is Li Chen for Arthur. Can you hear me okay?

這是亞瑟的李晨。你聽得到我說話嗎？

Yes.

是的。

Yes. So just upon the conversion from accelerated approval of ELAHERE to full approval, I believe that Takeda -- under the license agreement with Takeda, there's additional payment. Can you provide more details on that?

是的。因此，就在 ELAHERE 從加速批准轉換為完全批准時，我相信武田——根據與武田的許可協議，會有額外的付款。能否提供更多細節？

So I can comment on the Huadong license, and that does call for additional milestone payments upon full approval. I won't comment on the exact amount of those. I would have to get back to you on the Takeda license.

因此，我可以對華東許可證發表評論，這確實需要在完全批准後支付額外的里程碑付款。我不會評論這些的具體數量。我必須回覆您武田許可證問題。

Okay. Well, thank you all for joining us today. Obviously, we are very pleased with the progress in the business. We've got an important and growing product. We look forward to continued progress there. So we look to expand geographically and also moving this drug into earlier lines of therapy. We've got an important second pivotal program ongoing as we speak, an exciting portfolio. And you'll hear more from us as we go forward about reinvesting in the pipeline and our research capabilities.

好的。好的，謝謝大家今天加入我們。顯然，我們對業務的進展感到非常滿意。我們有一個重要且不斷成長的產品。我們期待在那裡繼續取得進展。因此，我們希望擴大地域範圍，並將這種藥物轉移到早期的治療中。就在我們說話的時候，我們正在進行第二個重要的關鍵計劃，這是一個令人興奮的投資組合。當我們繼續對管道和我們的研究能力進行再投資時，您會聽到我們更多的消息。

We think that ADCs are an important and growing class of therapeutics. We've got a highly differentiated skill set as it relates to that class of therapy. So again, I look forward to keeping you updated, and we'll see many of you at ASH. Thanks.

我們認為 ADC 是一類重要且不斷成長的治療藥物。我們擁有與此類治療相關的高度差異化的技能。再次強調，我期待為您提供最新消息，我們將在 ASH 上見到你們。謝謝。

Ladies and gentlemen, that does end our conference for today. Thank you for your participation. You may now disconnect.

女士們先生們，今天的會議到此結束。感謝您的參與。您現在可以斷開連線。