ImmunoGen Inc (IMGN) 2023 Q2 法說會逐字稿

Good morning, and welcome to ImmunoGen's Second 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.

早上好，歡迎參加ImmunoGen 2023 年第二季度財務和運營業績電話會議。今天的會議正在錄製中。現在，我想將電話轉給投資者關係主管 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 second quarter financial results. This press release, a recording of this call and an updated corporate deck can be found under the Investors and Media section of our website at immunogen.com.

早上好，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運營進展和第二季度財務業績的摘要。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 的投資者和媒體部分找到。

With me today are Mark Enyedy, our President and CEO; Isabel Kalofonos, our Chief Commercial Officer; Anna Berkenblit, our Chief Medical Officer; and Renee Lentini, our Interim CFO. Michael Vasconcelles, our EVP of Research, Development and Medical Affairs, will also join us for Q&A.

今天與我在一起的有我們的總裁兼首席執行官 Mark Enyedy； Isabel Kalofonos，我們的首席商務官； Anna Berkenblit，我們的首席醫療官；和我們的臨時首席財務官 Renee Lentini。我們的研究、開發和醫療事務執行副總裁 Michael Vasconcelles 也將加入我們的問答環節。

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.

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。我們將根據我們當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 上獲取）和immunogen.com。

With that, I'll turn the call over to Mark.

這樣，我會將電話轉給馬克。

Thanks, Anabel. Good morning, everyone, and thank you for joining us today. You will have seen this morning's press release announcing that Anna will be stepping down from her position as ImmunoGen's Chief Medical Officer, to take a well-deserved professional hiatus prior to pursuing new opportunities. I would like to take a moment to personally acknowledge and thank her for the essential role she has played in the transformation of this company.

謝謝，安娜貝爾。大家早上好，感謝您今天加入我們。您將會看到今天早上的新聞稿，宣布 Anna 將辭去 ImmunoGen 首席醫療官的職務，在尋求新機會之前進行一段理所應當的職業中斷。我想花一點時間親自承認並感謝她在公司轉型中所發揮的重要作用。

We've encountered no small amount of adversity as we navigated the last 4 years at ImmunoGen through it all Anna rose to the challenge with intellect, grit and good humor. Of particular note, she led the design and execution of the pivotal development program for ELAHERE that culminated in an FDA accelerated approval late last year and the unprecedented survival data shared at ASCO in June that have transformed the treatment landscape for patients with FR alpha positive ovarian cancer.

在過去 4 年裡，我們在 ImmunoGen 度過的過程中遇到了不小的逆境，安娜以智慧、勇氣和幽默感迎接了挑戰。特別值得注意的是，她領導了ELAHERE 關鍵開發項目的設計和執行，該項目最終在去年年底獲得了FDA 的加速批准，並於6 月份在ASCO 上分享了前所未有的生存數據，這些數據改變了FR α 陽性卵巢患者的治療前景癌症。

In parallel, under her leadership, we've also advanced our broader clinical pipeline, including a second pivotal program and built a highly talented development organization. Anna, I value you as a colleague and wish you the very best in your future endeavors. On behalf of ImmunoGen, our collaborators and most importantly, patients in need of more good days. Thank you.

與此同時，在她的領導下，我們還推進了更廣泛的臨床管道，包括第二個關鍵項目，並建立了一個高素質的開發組織。安娜，我重視你作為一名同事，並祝你在未來的工作中一切順利。我代表ImmunoGen、我們的合作者以及最重要的是需要更多美好時光的患者。謝謝。

Moving to our second quarter results. Since our last call, we made great progress on multiple fronts and achieved a significant milestone for patients in our organization with our confirmatory Phase III MIRASOL trial meeting not only the primary endpoint of progression-free survival, but also objective response rate and most importantly, overall survival. This is an unprecedented result in platinum-resistant ovarian cancer, making ELAHERE the first novel therapy to demonstrate an overall survival benefit versus chemotherapy in a Phase III trial. With these results now in hand, we anticipate submitting an MAA in Europe and the sBLA in the U.S., both in the fourth quarter of this year.

轉向我們的第二季度業績。自上次電話會議以來，我們在多個方面取得了巨大進展，並通過我們的驗證性III 期MIRASOL 試驗為我們組織中的患者實現了一個重要的里程碑，不僅達到了無進展生存期的主要終點，而且還達到了客觀緩解率，最重要的是，總體生存率。這是鉑類耐藥卵巢癌中前所未有的結果，使 ELAHERE 成為第一個在 III 期試驗中證明相對於化療具有總體生存獲益的新療法。有了這些結果，我們預計將在今年第四季度在歐洲提交 MAA，在美國提交 sBLA。

Turning to our commercial performance. We delivered a strong quarter with ELAHERE generating over $75 million and net sales more than doubling our Q1 result with increasing breadth and depth of adoption. Isabel will provide more detail on our progress with the launch in a moment. As an initial point, given that this is just our second full quarter on the market, coupled with recent developments with both ELAHERE and the broader ovarian cancer landscape, we have elected not to provide full year guidance for ELAHERE revenue today. The basis for this decision is this. We simply have not yet accumulated sufficient data and experience to confidently project the trajectory for ELAHERE over the back half of this year. The key variables underlying this decision include evolution of treatment rates, given the compelling efficacy of ELAHERE, we believe treatment rates may be increasing over historical benchmarks, particularly for later line patients. Shifting from prevalent to incident populations, which may potentially affect the growth rate of new patient starts.

轉向我們的商業表演。我們的季度表現強勁，ELAHERE 創造了超過 7500 萬美元的收入，隨著採用廣度和深度的不斷增加，淨銷售額是第一季度業績的兩倍多。伊莎貝爾稍後將提供有關我們發布進展的更多詳細信息。首先，考慮到這只是我們在市場上的第二個完整季度，再加上 ELAHERE 和更廣泛的卵巢癌領域的最新發展，我們選擇今天不提供 ELAHERE 全年收入指引。這個決定的依據是這樣的。我們只是還沒有積累足夠的數據和經驗來自信地預測 ELAHERE 今年下半年的發展軌跡。這一決定背後的關鍵變量包括治療率的演變，鑑於 ELAHERE 令人信服的療效，我們相信治療率可能會比歷史基準有所增加，特別是對於晚期患者。從流行人群轉向發病人群，這可能會影響新患者的增長率。

Duration of therapy. The claims data, which lagged the market by 90 days or more are not mature enough for us to provide a reliable forecast of how long patients are remaining on therapy at this time. Mix of testing and initial diagnosis versus testing to initiate treatment. And finally, monotherapy versus combination use. We are tapping multiple data sources to assess the percentage of combination use which have yielded somewhat disparate outputs up to this point.

治療持續時間。索賠數據滯後於市場 90 天或更長時間，還不夠成熟，無法讓我們對患者目前仍需接受治療的時間進行可靠預測。混合測試和初步診斷與測試以開始治療。最後，單一療法與聯合使用。我們正在利用多個數據源來評估組合使用的百分比，到目前為止，這些數據已經產生了一些不同的輸出。

Our clinical data suggests that combination use tends to generate higher response rates and longer durations of response. So an accurate assessment of this use is important. You will appreciate that each of these variables can have a significant impact on adoption and adherence to better assess the evolving market here, we have commissioned a demand study with the goal of increasing our confidence in assessing trends and the growth trajectory for the product.

我們的臨床數據表明，聯合使用往往會產生更高的緩解率和更長的緩解持續時間。因此，準確評估這種用途非常重要。您會意識到，這些變量中的每一個都可以對採用和遵守產生重大影響，以便更好地評估不斷變化的市場，我們委託進行了一項需求研究，目的是增強我們對評估產品趨勢和增長軌蹟的信心。

In addition, our existing vendors are updating their databases, and we are evaluating additional sources to gather more insights into the market. We look forward to updating you on our progress on these activities during subsequent calls.

此外，我們現有的供應商正在更新他們的數據庫，我們正在評估其他來源以收集更多關於市場的見解。我們期待在後續電話會議中向您通報這些活動的最新進展。

In terms of ongoing development, we are advancing our efforts to move ELAHERE into broader patient populations and to position it as the combination of choice in ovarian cancer. We look forward to our next milestone for the ELAHERE program with ORR data from our PICCOLO trial expected before the end of the year.

在持續開發方面，我們正在努力將 ELAHERE 推向更廣泛的患者群體，並將其定位為卵巢癌治療的首選組合。我們期待著 ELAHERE 項目的下一個里程碑，我們的 PICCOLO 試驗的 ORR 數據預計將在今年年底前實現。

Moving to our PVEK program. We've completed enrollment in the pivotal de novo patient cohort of the CADENZA trial and expect top line data in 2024. In addition, we progressed our 802 trial with PVEK in combination with VEN-AZA, for newly diagnosed AML patients and look forward to reporting data from these frontline cohorts at ASH later this year. Looking at the rest of the pipeline, IMGC936 and IMGN151 are progressing and we remain focused on reinvesting in our research capabilities and expanding our pipeline.

轉向我們的 PVEK 計劃。我們已經完成了 CADENZA 試驗的關鍵從頭患者隊列的入組，預計將於 2024 年獲得頂線數據。此外，我們還針對新診斷的 AML 患者開展了 PVEK 聯合 VEN-AZA 的 802 試驗，並期待今年晚些時候將在ASH 報告這些一線人群的數據。看看其餘的產品線，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。

Together with a strong balance sheet bolstered by our follow-on offering, our progress over the first 6 months of the year has positioned us well to create meaningful value for our patients and our shareholders in the second half of 2023 and well beyond. With that, I'll turn the call over to Isabel to cover our commercial progress. Isabel?

加上後續產品支撐的強勁資產負債表，今年前 6 個月的進展使我們能夠在 2023 年下半年及以後為患者和股東創造有意義的價值。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. We continue to successfully execute across the 4 launch imperatives as we work to position ELAHERE as the standard of care portfolio receptor alpha positive ovarian cancer. In the second quarter, we generated $77.4 million in net sales. We are very pleased with another strong quarter of performance and believe this is due to the combination of factors, including the solid execution of the commercial teams, robust engagement by our medical team increased breadth and depth of adoption driven by recognition of the benefits, this novel treatment brings to patients with advanced ovarian cancer and the compelling MIRASOL data increasing awareness and interest from both patients and physicians. Uptake in the quarter continues to be brought and deep with a significant percentage of accounts with repeat orders complemented by consistent ordering from these accounts while academic institutions comprise our largest customer, roughly 65% of orders during the quarter came from nonacademic institutions and community-based oncology groups versus 70% in the first quarter.

謝謝你，馬克。我們繼續成功執行 4 項上市要求，努力將 ELAHERE 定位為受體 α 陽性卵巢癌治療組合的標準。第二季度，我們實現了 7740 萬美元的淨銷售額。我們對又一個強勁的季度業績感到非常高興，並相信這是多種因素共同作用的結果，包括商業團隊的紮實執行、我們醫療團隊的積極參與、由於對好處的認可而增加了採用的廣度和深度，這新穎的治療方法為晚期卵巢癌患者帶來了新的治療方法，而令人信服的 MIRASOL 數據也提高了患者和醫生的認識和興趣。本季度的吸收繼續深入，相當大比例的帳戶有重複訂單，並通過這些帳戶的一致訂購進行補充，而學術機構是我們最大的客戶，本季度大約 65% 的訂單來自非學術機構和社區腫瘤學組的比例在第一季度為70%。

We anticipate the mix of orders to continue to shift with an increase in percentage coming from academic accounts as satellite centers of major academic institutions start infusion. Regarding testing in response to the continued strong demand for the folate receptor diagnostic tests, additional labs are actively being certified to run the test. As of the end of the quarter, we had 33 labs comprised of 15 centralized labs and 18 in-house labs, fully certified with 15 additional labs in the process of validation. Of note, as testing becomes more decentralized we'll have the decreased visibility into the number of tests performed.

我們預計，隨著主要學術機構的衛星中心開始注入資金，來自學術賬戶的訂單比例將繼續發生變化。為了滿足對葉酸受體診斷測試的持續強勁需求，其他實驗室正在積極獲得運行測試的認證。截至本季度末，我們擁有 33 個實驗室，其中包括 15 個集中實驗室和 18 個內部實驗室，並已獲得全面認證，另有 15 個實驗室正在驗證過程中。值得注意的是，隨著測試變得更加分散，我們對所執行測試數量的可見性將會降低。

Based on the information visible to us, we estimate that roughly 11,800 tests have been performed launch to date through the end of June with a significant percentage of this test being for newly diagnosed patients. In addition, the folate receptor as a positive rate remains between 35% and 40%, in line with our expectations.

根據我們掌握的信息，我們估計截至 6 月底為止，已進行了大約 11,800 次測試，其中很大一部分測試是針對新診斷的患者。此外，葉酸受體的陽性率保持在35%至40%之間，符合我們的預期。

Moving on to access. We continue to be very pleased with how quickly payers have included ELAHERE and coverage policies aligned with our label. We ended the quarter with roughly 95% of both Medicare and commercial lives covered. Lastly, our customer-facing field teams remain highly active.

繼續訪問。我們仍然對付款人如此迅速地納入 ELAHERE 以及與我們的標籤一致的承保政策感到非常滿意。本季度末，我們承保了大約 95% 的醫療保險和商業保險。最後，我們面向客戶的現場團隊仍然高度活躍。

As of the end of June, our commercial team has engaged roughly 90% of their priority targets, and our medical affairs team continues to provide a full suite of support to ensure positive physician and patient experiences.

截至 6 月底，我們的商業團隊已參與了大約 90% 的優先目標，我們的醫療事務團隊繼續提供全套支持，以確保積極的醫生和患者體驗。

Reports from the field consistently relate enthusiastic feedback from clinicians regarding their experience with ELAHERE, which is a testament to our customer and healthcare professional phase in organization.

來自現場的報告一致反映了臨床醫生對 ELAHERE 體驗的熱情反饋，這證明了我們的客戶和醫療保健專業人員在組織中的階段。

In summary, we are very pleased with our performance and look forward to carrying this momentum into the second half of the year.

總而言之，我們對我們的表現感到非常滿意，並期待將這一勢頭延續到下半年。

With that, I would like to turn the call over to Anna to provide additional color on the Mirasol data on our ongoing development program. Anna?

說到這裡，我想將電話轉給 Anna，為我們正在進行的開發計劃的 Mirasol 數據提供更多信息。安娜？

Thanks, Isabel. Before I get into my update, thank you, Mark, for your kind words at the top of today's call. It has been a pleasure and a privilege to serve this organization. I take immense pride and having been part of this leadership team and having built a clinical development team comprised of top talent that executed effectively during a global pandemic, leading to the accelerated approval of ELAHERE with a broader-than-anticipated initial label and the first ever overall survival benefit for a novel therapy in platinum-resistant ovarian cancer. What we have done together is remarkable. Thank you for the opportunities you have given me and for your leadership.

謝謝，伊莎貝爾。在介紹最新情況之前，馬克，謝謝你在今天的電話會議上所說的客氣話。為這個組織服務是我的榮幸。我非常自豪能夠成為這個領導團隊的一員，並建立了一支由頂尖人才組成的臨床開發團隊，在全球大流行期間有效執行，導致ELAHERE 加速獲得批准，其初始標籤範圍比預期更廣泛，並且是第一個鉑耐藥卵巢癌新療法的總體生存獲益。我們共同所做的事情是非凡的。感謝您給我的機會以及您的領導。

Now moving on to our review of the clinical programs. We were thrilled that shortly after we press released the top line data on May 3, Dr. Kathleen Moore was able to present the key efficacy and safety results from the confirmatory MIRASOL trial in a late-breaker oral presentation at ASCO in early June. Since then, we have continued to engage with stakeholders across the ovarian cancer community and the enthusiasm for these data and the broader mirvetuximab program is high. As a reminder, MIRASOL is the randomized confirmatory Phase III trial of mirvetuximab versus investigator's choice with chemotherapy, weekly paclitaxel, pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer whose tumors express high levels of folate receptor alpha and who have received up to 3 prior regimens. The trial was a resounding success, and we are pleased that our compelling efficacy data with an unprecedented overall survival advantage were complemented by a consistent safety profile aligned to our prior clinical trial experience.

現在繼續我們對臨床計劃的審查。我們很高興在 5 月 3 日發布主要數據後不久，Kathleen Moore 博士就能夠在 6 月初在 ASCO 的最新口頭報告中介紹 MIRASOL 驗證性試驗的關鍵療效和安全性結果。從那時起，我們繼續與卵巢癌界的利益相關者進行接觸，對這些數據和更廣泛的 mirvetuximab 項目的熱情很高。提醒一下，MIRASOL 是一項隨機驗證性III 期試驗，比較mirvetuximab 與研究者選擇的化療、每周紫杉醇、聚乙二醇化脂質體多柔比星或託泊替康，治療腫瘤表達高水平葉酸受體α 且已接受化療的鉑耐藥性卵巢癌患者。至 3 個先前的治療方案。該試驗取得了巨大成功，我們很高興看到我們令人信服的療效數據以及前所未有的總體生存優勢，並得到與我們之前的臨床試驗經驗一致的一致安全性的補充。

Starting with safety. The AE profile continues to consist of predominantly low-grade ocular and gastrointestinal events with no new safety signals identified. Notably, compared with chemotherapy, MIRV was associated with lower rates of grade 3 or greater treatment-emergent adverse events, serious adverse events and importantly, a lower rate of treatment-emergent adverse events leading to discontinuation of study drug.

從安全開始。 AE 概況仍然主要由低級別的眼部和胃腸道事件組成，沒有發現新的安全信號。值得注意的是，與化療相比，MIRV 與3 級或以上治療中出現的不良事件、嚴重不良事件的發生率較低相關，更重要的是，導致研究藥物停藥的治療中出現的不良事件發生率較低。

On the primary efficacy endpoint of progression-free survival by investigator, MIRASOL achieved a hazard ratio of 0.65 and a p-value of less than 0.0001, representing a 35% reduction in the risk of progression or death for the ELAHERE treated population compared with chemotherapy. The key secondary endpoint objective response rate was also highly statistically significant. On the MIRV arm, ORR was nearly triple compared to chemotherapy at 42.3% with 12 complete responses compared with 15.9% and no complete responses on the chemotherapy control arm as reported by investigators.

在研究者無進展生存期的主要療效終點上，MIRASOL 實現了 0.65 的風險比和小於 0.0001 的 p 值，這意味著與化療相比，ELAHERE 治療人群的進展或死亡風險降低了 35% 。關鍵次要終點客觀緩解率也具有高度統計顯著性。據研究人員報告，MIRV 組的 ORR 幾乎是化療的三倍，為 42.3%，有 12 例完全緩解，而化療對照組為 15.9%，沒有完全緩解。

PFS and ORR results by blinded independent central review were concordant with investigator assessment. Turning to the most meaningful clinical endpoint, overall survival with 204 events reported ELAHERE demonstrated a statistically significant improvement in survival compared to chemotherapy with a hazard ratio of 0.67 and a p-value of 0.0046. This corresponds to a 33% reduction in the risk of death with ELAHERE compared to chemotherapy. The median overall survival with ELAHERE was 16.46 months compared with 12.75 months on the chemotherapy control arm.

通過盲法獨立中央審查得出的 PFS 和 ORR 結果與研究者評估一致。轉向最有意義的臨床終點，ELAHERE 報告的 204 個事件的總生存率顯示，與化療相比，生存率有統計學顯著性改善，風險比為 0.67，p 值為 0.0046。與化療相比，ELAHERE 治療的死亡風險降低了 33%。 ELAHERE 組的中位總生存期為 16.46 個月，而化療對照組的中位總生存期為 12.75 個月。

As Mark noted earlier, ELAHERE is the first drug to demonstrate an OS benefit in a Phase III trial in platinum-resistant ovarian cancer. Quite simply, these data are practice-changing.

正如 Mark 之前指出的，ELAHERE 是第一個在鉑耐藥性卵巢癌 III 期試驗中證明具有 OS 益處的藥物。很簡單，這些數據正在改變實踐。

Let me now turn to the broader mirvetuximab development program, which has the potential to meaningfully expand the ELAHERE label by moving into platinum-sensitive disease and positioning MIRV as the combination agent of choice in ovarian cancer. Specifically, we are progressing 3 studies.

現在讓我談談更廣泛的 mirvetuximab 開發計劃，該計劃有可能通過進入鉑類敏感疾病並將 MIRV 定位為卵巢癌的首選聯合用藥，從而有意義地擴展 ELAHERE 標籤。具體來說，我們正在進行 3 項研究。

The first is PICCOLO, a single-arm Phase II trial evaluating MIRV monotherapy in folate receptor alpha high platinum-sensitive ovarian cancer. Enrollment was completed in January, and we anticipate sharing ORR data by the end of this year with duration of response data expected in 2024. The second is GLORIOSA, our Phase III trial evaluating MIRV plus bevacizumab maintenance versus standard of care bevacizumab maintenance in the second-line platinum-sensitive setting. This study levers our robust MERV plus BEV data in the treatment setting, which led to NCCN Compendium listing for MIRV BEV in platinum-resistant ovarian cancer into the platinum-sensitive maintenance setting, where patients may stand to benefit from even longer durations of therapy.

第一個是 PICCOLO，這是一項單臂 II 期試驗，評估 MIRV 單藥療法治療葉酸受體 α 高鉑敏感卵巢癌的效果。入組工作已於1 月份完成，我們預計在今年年底之前共享ORR 數據，預計緩解數據的持續時間將在2024 年完成。第二個是GLORIOSA，我們的III 期試驗評估MIRV 加貝伐單抗維持與標準護理貝伐單抗維持在第二個試驗中的效果線鉑金敏感設置。這項研究利用了我們在治療環境中可靠的MERV 加BEV 數據，這導致NCCN 綱要將鉑類耐藥卵巢癌中的MIRV BEV 納入鉑敏感維持環境中，患者可能會從更長的治療持續時間中受益。

And the third is Trial 420, a single-arm Phase II trial evaluating MIRV plus carboplatin followed by MIRV continuation in platinum-sensitive ovarian cancer patients with low, medium or high levels of folate receptor alpha expression.

第三個是試驗 420，這是一項單組 II 期試驗，評估 MIRV 加卡鉑，然後繼續使用 MIRV，治療葉酸受體 α 表達水平低、中或高的鉑敏感卵巢癌患者。

Both combination trials, GLORIOSA and Trial 420 are enrolling in the U.S. and are getting going in Europe.

GLORIOSA 和 Trial 420 兩項聯合試驗均已在美國入組，並正在歐洲開展。

Moving to our second typical program. We presented data from an interim analysis of the Phase II Cadenza trial of PVEK in patients with frontline and relapsed/refractory BPDCN at the EHA or EHA conference in June. PVEK demonstrated encouraging clinical activity and tolerability, especially in light of the toxicities of the available therapy.

轉向我們的第二個典型程序。我們在 6 月份的 EHA 或 EHA 會議上展示了 PVEK 在一線和復發/難治性 BPDCN 患者中進行的 II 期 Cadenza 試驗的中期分析數據。 PVEK 表現出令人鼓舞的臨床活性和耐受性，特別是考慮到現有療法的毒性。

In the frontline setting, we observed a composite CR rate of over 70% and a median duration of response of over 12 months in the relapsed/refractory setting, which included patients previously treated with PVAC plus, we observed a CCR rate of 20% and a median duration of response of over 7 months. Commensurate with the increasing awareness of the potential of PVAC in this ultra-rare indication, we are pleased to share that we have completed enrollment in the pivotal frontline de novo BPDCN cohort of CADENZA and anticipate top line data in 2024.

在一線環境中，我們觀察到復發/難治性環境中的綜合CR 率超過70%，中位緩解持續時間超過12 個月，其中包括先前接受PVAC 加治療的患者，我們觀察到CCR 率為20 %，中位緩解持續時間超過 7 個月。隨著人們對PVAC 在這種極其罕見的適應症中的潛力的認識不斷提高，我們很高興地告訴大家，我們已經完成了CADENZA 關鍵一線新BPDCN 隊列的入組，並預計2024 年將獲得頂線數據。

For our 802 trial of PVEK, in combination with venetoclax and azacitidine in frontline AML, we have enrolled 25 patients in both the venetoclax 14 days plus and the 28-day minus triplet cohorts. These data will help us optimize the duration of the venetoclax for the triplet and guide pivotal development in frontline AML. We look forward to reporting data from these cohorts at ASH later this year.

在我們的 802 項 PVEK 試驗中，結合 Venetoclax 和阿扎胞苷治療一線 AML，我們在 Venetoclax 14 天加和 28 天減三聯隊列中招募了 25 名患者。這些數據將幫助我們優化三聯體的維奈托克的持續時間，並指導一線 AML 的關鍵開發。我們期待在今年晚些時候在 ASH 上報告這些隊列的數據。

As for our earlier-stage assets on IMGC936, our first-in-class ADAM9-targeting ADC in co-development with MacroGenics enrollment progressed in 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 expect later this year. Lastly, we are progressing our Phase I trial of IMGN151, our next-generation anti-folate 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.

至於我們在 IMGC936 上的早期資產，我們與 MacroGenics 共同開發的一流 ADAM9 靶向 ADC 在我們的非小細胞肺癌擴展隊列中取得了進展，我們計劃在指定的協議後提供更新中期分析已完成，我們預計將在今年晚些時候完成。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。

In closing, I want to thank all my ImmunoGen colleagues for their ongoing commitment to delivering more good days for patients with cancer. I will cherish my time with this business, both professionally and personally. As to what's next, I look forward to spending time with my family continuing my board work and pursuing consulting in the coming months while I watch ImmunoGen's bright future unfold.

最後，我要感謝所有免疫基因同事一直致力於為癌症患者帶來更多美好的日子。我會珍惜在這個行業的時間，無論是在職業上還是個人上。至於接下來的事情，我期待著在接下來的幾個月裡與家人一起繼續我的董事會工作並尋求諮詢服務，同時我會看到ImmunoGen 光明的未來展現出來。

With that, I'll turn the call over to Renee to cover our financials. Renee?

這樣，我會將電話轉給蕾妮，詢問我們的財務狀況。蕾妮？

Thanks, Anna. For the second quarter of 2023, we generated $83.2 million in revenue, including $77.4 million in net product sales of ELAHERE and the remainder from noncash royalty revenues. Operating expenses were $86.5 million, comprised of $50.1 million of R&D expenses and $36.4 million of SG&A expenses. In May, pursuant to an equity offering, we further strengthened our balance sheet, generating approximately $351 million in net proceeds. We ended the second quarter with $572 million in cash on the balance sheet.

謝謝，安娜。 2023 年第二季度，我們實現了 8320 萬美元的收入，其中包括 ELAHERE 的產品淨銷售額 7740 萬美元，其餘部分來自非現金特許權使用費收入。運營費用為 8,650 萬美元，其中包括 5,010 萬美元的研發費用和 3,640 萬美元的銷售、一般管理費用。 5 月份，根據股票發行，我們進一步強化了資產負債表，產生了約 3.51 億美元的淨收益。第二季度結束時，我們的資產負債表上有 5.72 億美元的現金。

Our financial guidance for 2023 has been updated, and we now expect operating expenses between $350 million and $365 million. This increase reflects greater spending in support of ELAHERE including preparations for a launch in Europe in addition to expanding our research capabilities and pipeline. Revenue guidance, excluding ELAHERE sales remains unchanged at between $45 million and $50 million. We expect that our existing cash and cash equivalents, together with anticipated future products and collaboration revenues will fund operations for more than 2 years. With that, we'll open the call for questions.

我們更新了 2023 年的財務指引，目前預計運營費用在 3.5 億至 3.65 億美元之間。這一增長反映出支持 ELAHERE 的支出增加，包括除了擴大我們的研究能力和管道之外，還準備在歐洲推出。收入指引（不包括 ELAHERE 銷售額）保持在 4500 萬美元至 5000 萬美元之間不變。我們預計現有的現金和現金等價物以及預期的未來產品和合作收入將為兩年以上的運營提供資金。至此，我們將開始提問。

(Operator Instructions) The first question comes from John Newman with Canaccord.

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

So Anna, first, I just want to say congrats on all the great work at ImmunoGen. You'll certainly be missed. And the best companies in biotech are the ones that can execute their clinical studies near perfect and ImmunoGen certainly included in that bucket. Just had one question, which is we know that mirvetuximab in MIRASOL was tested in patients with FR alpha high confirmed by 3-plus expression level. Just curious if you can talk about whether you expect MIRV or I should say ELAHERE now will be used in patients with 2-plus expression levels and perhaps if we're seeing that at the moment.

因此，安娜，首先，我只想對 ImmunoGen 所做的所有出色工作表示祝賀。你一定會被想念的。生物技術領域最好的公司是那些能夠近乎完美地執行臨床研究的公司，ImmunoGen 無疑也屬於其中。只是有一個問題，我們知道 MIRASOL 中的 mirvetuximab 在 FR α 高的患者中進行了測試，經 3+ 表達水平證實。只是好奇你是否可以談談你是否期望 MIRV 或者我應該說 ELAHERE 現在將用於表達水平超過 2 的患者，也許我們目前正在看到這一點。

Thanks, John. Thank you for your kind words. Just to clarify, the definition of FR alpha high expression by our companion diagnostic is at least 75% of tumor cells, at least 2-plus positive by immunohistochemistry staining, so 2 plus and 3 plus. And that comprises between 35% and 40% of all ovarian cancer patients and the commercial testing has performed as we've seen in clinical trials. We have previously explored mirvetuximab in patients with lower levels of FR alpha expression as monotherapy.

謝謝，約翰。感謝您的客氣話。澄清一下，我們的伴隨診斷對 FR α 高表達的定義是至少 75% 的腫瘤細胞，免疫組織化學染色至少 2+ 陽性，因此 2+ 和 3+。這佔所有卵巢癌患者的 35% 到 40%，商業測試的效果正如我們在臨床試驗中所看到的那樣。我們之前曾探索過米妥昔單抗作為單一療法治療 FR α 表達水平較低的患者。

As you can recall from FORWARD I, and we know from that study that patients with medium levels of FR alpha expression, which is at least 50% of cells. So medium is between 50% and 75% of cells with at least 2-plus expression by immunohistochemistry. And that encompasses about another 20% of ovarian cancer patients. We know that they do about as well with mirvetuximab as with investigator choice chemotherapy based on a post-hoc exploratory analysis and certainly, based on that data as well as some preclinical data that we have showing synergy with various agents, we are exploring patients with lower levels of FR alpha expression in our combination strategies.

正如您可以從 FORWARD I 中回憶起的那樣，我們從該研究中知道，患者俱有中等水平的 FR α 表達，至少有 50% 的細胞。因此，通過免疫組織化學檢測，培養基中 50% 至 75% 的細胞具有至少 2+ 的表達。這還包括大約另外 20% 的卵巢癌患者。我們知道，他們使用米妥昔單抗與基於事後探索性分析的研究者選擇化療效果一樣好，當然，根據這些數據以及我們顯示與各種藥物具有協同作用的一些臨床前數據，我們正在探索患有以下疾病的患者：我們的組合策略中 FR α 表達水平較低。

We also know that when we combine mirvetuximab with bevacizumab across a broad range of FR alpha expression, so low, medium and high, lows being at least 25% to 50% of cells with at least 2-plus expression that we get very nice data that were published earlier this year in the [Dynox] journal, and that led to compendia listing for MIRV plus BEV for patients with low, medium or high FR alpha expression, and that encompasses about 80% of ovarian cancer patients. Looking to the future, we're also combining MERV with carboplatin in patients with low, medium and high FR alpha expression in our 420 study. So our initial approval in patients with high FR alpha expression for MERV monotherapy is just the beginning.

我們還知道，當我們將mirvetuximab 與貝伐珠單抗結合使用時，FR α 表達範圍廣泛，包括低、中和高，低值是至少25% 至50% 的細胞具有至少2+ 的表達，我們得到了非常好的數據今年早些時候發表在[Dynox] 雜誌上，這導致MIRV 加BEV 的概要列出，用於治療低、中或高FR α 表達的患者，涵蓋約80% 的卵巢癌患者。展望未來，我們還在 420 名研究中將 MERV 與卡鉑聯合治療 FR α 低、中和高表達的患者。因此，我們對 FR α 高表達患者的 MERV 單藥治療的初步批准僅僅是一個開始。

If I could ask one quick additional question on combination with bevacizumab, just curious if you're seeing anything at the moment from your data with regard to perhaps the uptake their combination with the best.

如果我可以問一個關於與貝伐珠單抗組合的快速附加問題，我只是好奇您目前是否從數據中看到了有關其與最佳組合的吸收情況的任何信息。

Yes. The answer is yes. So when we look at the claims data, and I'm sure we'll have lots of questions on that. It's early days, but we absolutely do see combination use as part of the claims set and the feedback that we get anecdotally certainly supports that.

是的。答案是肯定的。因此，當我們查看索賠數據時，我確信我們對此會有很多疑問。現在還處於早期階段，但我們確實看到組合使用是聲明中的一部分，並且我們得到的反饋肯定支持這一點。

The next question comes from Michael Schmidt with Guggenheim.

下一個問題來自古根海姆的邁克爾·施密特。

Congrats on another very strong quarter. And let me just add my congratulations to Anna as far as all the success at ImmunoGen you will be missed, obviously, by many. I have a question on the evolving testing paradigm. So in our due diligence, we've heard that many of the large academic institutions prefer in-house testing over using the centralized labs that you have established and I was wondering if you could confirm that and how many of the big centers are not yet certified for in-house testing in the U.S?

祝賀又一個非常強勁的季度。讓我向 Anna 表示祝賀，顯然，很多人都會想念你在 ImmunoGen 所取得的成功。我有一個關於不斷發展的測試範式的問題。因此，在我們的盡職調查中，我們聽說許多大型學術機構更喜歡內部測試，而不是使用您建立的集中實驗室，我想知道您是否可以證實這一點，以及有多少大型中心還沒有這樣做獲得美國內部測試認證？

Thank you. As you know, we had a very strong demand for testing so far. And in the second quarter, we surpassed 11,400 tests. And now we are over [17,000]tests. We can confirm that as of today. And when it comes to the labs, we have 33 labs that are operational, of which 15 are academic centers. And in those centers, we have less visibility about the data that we have. In process, we have another 15 labs that are in the process of being certified. So we continue to see very strong testing, as I just mentioned.

謝謝。如您所知，到目前為止我們對測試的需求非常強烈。第二季度，我們進行了超過 11,400 次測試。現在我們已經進行了超過 [17,000] 次測試。截至今天，我們可以確認這一點。說到實驗室，我們有 33 個正在運行的實驗室，其中 15 個是學術中心。在這些中心，我們對所擁有的數據的可見性較低。目前，我們還有另外 15 個實驗室正在接受認證。因此，正如我剛才提到的，我們繼續看到非常強大的測試。

Okay. And regarding the PICCOLO study, how should we think about the regulatory bar for response rate in that platinum-sensitive setting? Is the bar similar to that was applied to the SORAYA study, for example, or is it higher or lower?

好的。關於 PICCOLO 研究，我們應該如何考慮鉑類敏感環境中緩解率的監管門檻？例如，該標準與 SORAYA 研究中應用的標準相似，還是更高或更低？

I think the bar is to be determined, Michael, because the landscape has evolved with the incorporation of PARP inhibitor maintenance particularly now in the frontline setting. And we know from multiple studies that unfortunately PARP maintenance therapy seems to induce resistance to subsequent DNA damaging agents, particularly things like platinum as well as topotecan and Doxil, which also are DNA damaging agents. But what that means is that patients who are technically platinum-sensitive post a PARP inhibitor. In other words, they've recurred greater than 6 months after the last dose of their last platinum may not be as sensitive to platinum as they were previously.

我認為這個標準還有待確定，邁克爾，因為隨著 PARP 抑製劑維護的納入，情況已經發生了變化，特別是現在在前線環境中。我們從多項研究中得知，不幸的是，PARP 維持治療似乎會誘導對後續 DNA 損傷劑的耐藥性，特別是鉑、拓撲替康和 Doxil 等藥物，它們也是 DNA 損傷劑。但這意味著技術上對鉑敏感的患者需要使用 PARP 抑製劑。換句話說，他們在最後一次鉑類藥物最後一劑後超過 6 個月復發，可能不再像以前那樣對鉑類敏感。

So that coupled with the fact that there were not -- there are no robust randomized Phase III Level 1 evidence studies in later line platinum-sensitive disease to begin with, even in the pre-PARP days, we don't really know what the benchmark is. That said, more studies are coming out, again, showing that more platinum for these post-PARP patients may not be in their best interest. So the way we're thinking about it is that the higher the response rate, the longer the duration of response in PICCOLO, the easier the conversation will be with regulators about what an appropriate bar would be for us to beat. So at this point, we're really excited about the PICCOLO study. We're on track for ORR data before the end of the year. We know these patients are doing well, and so we will anticipate having DOR data next year.

因此，再加上事實上，即使在 PARP 之前的日子裡，也沒有針對後期鉑敏感疾病進行強有力的隨機 III 期 1 級證據研究，我們真的不知道基準是。也就是說，越來越多的研究再次表明，對於這些 PARP 後患者來說，更多的鉑可能不符合他們的最佳利益。因此，我們的想法是，響應率越高，PICCOLO 的響應持續時間越長，與監管機構討論我們需要打破的適當標準就越容易。因此，此時此刻，我們對 PICCOLO 研究感到非常興奮。我們有望在年底前獲得 ORR 數據。我們知道這些患者狀況良好，因此我們預計明年將獲得 DOR 數據。

Okay. And then last question, just regarding the 802 study of PVEK in AML, could you just remind us of the 2 cohorts that you're running in frontline? And what are you looking for here in the ASH data that would support initiation of Phase III trials? Is it a primary look at safety or certain efficacy measures are important as well for you?

好的。最後一個問題，關於 PVEK 在 AML 中的 802 研究，您能提醒我們一下您在一線進行的 2 個隊列嗎？您在 ASH 數據中尋找什麼來支持 III 期試驗的啟動？這是對安全性的主要考慮還是某些功效措施對您也很重要？

Sure. So just as background, Ven-AZA has become the new standard of care for unfit frontline AML patients, which is about all of -- about half of AML patients, although even the definition of unfit is being evolved so that more patients do get VEN-AZA. That said, it's a tough regimen in and of itself at the labeled doses and schedules. Many compounds have tried to combine with VEN-AZA, and have failed because of just excess toxicity of the triplets. Ours is not one of those. We are one of the few that has been able to combine successfully. And so we started out, I would say, in an appropriately conservative manner to protect patient safety with what's called a 14-day plus regimen of venetoclax in the relapsed/refractory setting.

當然。因此，正如背景一樣，Ven-AZA 已成為不健康的一線 AML 患者的新護理標準，這大約佔 AML 患者的一半左右，儘管甚至不健康的定義也在不斷發展，以便更多的患者確實接受 VEN -阿扎。也就是說，按照標籤上的劑量和時間表，這本身就是一個艱難的治療方案。許多化合物嘗試與 VEN-AZA 結合，但由於三聯體的毒性過多而失敗。我們的不是其中之一。我們是少數能夠成功合併的公司之一。因此，我想說，我們開始以適當保守的方式，在復發/難治性環境中使用所謂的 14 天加維奈托克療法來保護患者安全。

We proved safety of that regimen and moved it up into the frontline setting, where we had 10 patients worth of data we presented at ASH last year with the 14-day plus regimen. In conversation with FDA, FDA made it clear their expectation is that we combine with a standard or a labeled dose and schedule of VEN-AZA and venetoclax is generally given per label up to 28 days in a row. But the problem is many patients can't tolerate that extended duration of venetoclax because of profound myelosuppression. And so we have basically completed accrual now in 25 patients using what we call the 14-day plus and 25 patients in the 28-day minus regimens. So what happens is for each of these patients do get a bone marrow around 14 days in the 14-day plus or later in the 28-day minus and regimen.

我們證明了該方案的安全性，並將其轉移到一線環境中，去年我們在 ASH 上展示了 10 名患者的 14 天加方案數據。在與 FDA 的對話中，FDA 明確表示他們的期望是我們將 VEN-AZA 與標准或標籤劑量和時間表相結合，並且 Venetoclax 通常按照標籤連續 28 天給藥。但問題是，許多患者由於嚴重的骨髓抑製而無法耐受延長的維奈托克治療時間。因此，我們現在基本上已經完成了 25 名患者使用我們所謂的 14 天+ 方案的累積治療，以及 25 名患者使用我們所謂的 28 天減號方案的累積治療。因此，對於這些患者中的每一位來說，在 14 天加號或 28 天減號方案中的 14 天左右都會獲得骨髓。

And if patients have residual blasts, they continue with the venetoclax, if the bone marrow shows no blast, then they stop the venetoclax because at that point, venetoclax would just be adding toxicity. And so we're going to combine the data from those sets to understand the safety of the triplets, understand the efficacy both in terms of CR rate as well as MRD or measurable residual disease rate. And both safety and efficacy will guide how we're thinking about a frontline pivotal triplet AML registrational trial. So stay tuned for ASH.

如果患者有殘留的原始細胞，他們會繼續使用維奈托克，如果骨髓顯示沒有原始細胞，那麼他們會停止使用維奈托克，因為此時，維奈托克只會增加毒性。因此，我們將結合這些數據集的數據來了解三胞胎的安全性，了解 CR 率以及 MRD 或可測量殘留病率方面的功效。安全性和有效性將指導我們如何考慮一線關鍵三聯體 AML 註冊試驗。所以請繼續關注 ASH。

Our next question comes from 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 wanted of -- my congratulations and I also wanted to mention as it has been a pleasure talking to you, Anna, and best of luck with the next step. Just as we think about the duration of use, I wonder if you could kind of provide some color. It sounds like it's a range you're getting from your estimates, but if there's anything you can give around that range for the duration of use, kind of the line of therapy and whether you're mostly seeing it in combination with Bev?

只是想——我的祝賀，我也想提一下，因為很高興與你交談，安娜，祝下一步好運。正如我們考慮使用的持續時間一樣，我想知道您是否可以提供一些顏色。聽起來這似乎是您根據估計得出的一個範圍，但如果在使用期間您可以在該範圍內提供任何信息，治療方案的類型以及您是否主要將其與 Bev 結合使用？

So it starts with the claims data, right? And so it trickles in. So as we gather those data. So for example, if you look at the last claims data I saw was earlier this month, we had 4 patients reported, right? And so it's a little hard to think about extrapolating that over the back half of the year when you sort of have to back up the 90 days and try and accumulate the totality of the experience and then project that forward. And so duration of therapy falls exactly into that bucket, which is -- it's difficult to ascertain at this point. When we look at the accounts versus the claims data to assess what's happening commercially with the brand at this point.

所以它從索賠數據開始，對吧？所以當我們收集這些數據時，它就會慢慢地進來。舉例來說，如果你看一下我在本月早些時候看到的最後一次索賠數據，我們報告了 4 名患者，對嗎？因此，要在今年下半年進行推斷有點困難，因為你必須回溯 90 天，嘗試積累全部經驗，然後將其向前推進。因此，治療持續時間恰好屬於這一範圍，目前很難確定。當我們查看賬戶與索賠數據來評估該品牌目前的商業狀況時。

And so -- our experience that we've related is with the SORAYA data where it's complete, where we saw a mean number of cycles 7 in that population. That population certainly was the most heavily pretreated that we've observed in our clinical experience. And so I think that's a baseline for duration of therapy. What we can say, Peter, generally, is that in the initial stages of the launch, the claims data indicate that we were starting in later line patients particularly with the MIRASOL data, what we see is moving into earlier line patients, which we think will correspond with longer durations of therapy generally.

因此，我們的經驗是與 SORAYA 數據相關的，它是完整的，我們在該群體中看到平均週期數為 7。該人群無疑是我們在臨床經驗中觀察到的接受最嚴格預處理的人群。所以我認為這是治療持續時間的基線。 Peter，總的來說，我們可以說的是，在啟動的初始階段，索賠數據表明我們是從後期患者開始，特別是 MIRASOL 數據，我們看到的是進入早期患者，我們認為通常與較長的治療持續時間相對應。

In addition to that, what we see are combination use, the results from that, as we shared in the prepared remarks for today, are disparate across the databases. So we're making a concerted effort to try and reconcile those databases and supplement that with a demand study in order to get a better assessment of what's going on. But it was those factors. As we think about this, the commercial team here has put together essentially a matrix. And on one axis is the impact that it has on revenue and on the other is our confidence level. So when we look at things that have high impact and high confidence, we include there our FR alpha positivity rate because we've run the experiment on over 13,000 tests and have a pretty high degree of confidence in terms of the positivity rate.

除此之外，我們看到的是組合使用，正如我們在今天準備的評論中分享的那樣，其結果在各個數據庫中是不同的。因此，我們正在齊心協力嘗試協調這些數據庫，並通過需求研究對其進行補充，以便更好地評估正在發生的情況。但正是這些因素。當我們思考這個問題時，這裡的商業團隊本質上已經構建了一個矩陣。一方面是它對收入的影響，另一方面是我們的信心水平。因此，當我們考慮具有高影響力和高置信度的事物時，我們會將 FR alpha 陽性率納入其中，因為我們已經對超過 13,000 次測試進行了實驗，並且對陽性率具有相當高的置信度。

In terms of duration of therapy, we just -- we simply have an incomplete data set when we look over the claims data. And similarly, we just see an evolving picture in terms of lines of therapy. So again, it's something that we are working on aggressively in order to have a very clear view of the market that we could articulate to the investment community.

就治療持續時間而言，當我們查看索賠數據時，我們只是擁有不完整的數據集。同樣，我們只是看到治療方案不斷演變的情況。再說一次，我們正在積極致力於這件事，以便對市場有一個非常清晰的看法，以便我們可以向投資界闡明。

Got you. Your conversations with physicians, does that point into most of the combination use? Or is it again, kind of a broad range?

明白你了。您與醫生的對話是否表明大多數聯合用藥都是如此？或者又是一個寬泛的範圍？

We see a significant percentage. We have physicians report to us in their practices that a significant percentage of the uses in combination.

我們看到了很大的比例。我們的醫生在他們的實踐中向我們報告說，很大比例的藥物是聯合使用的。

The next question comes from Etzer Darout with BMO Capital Markets.

下一個問題來自 BMO 資本市場的 Etzer Darout。

Great. Congrats on the quarter and also would like to echo my colleagues sentiment on the contribution Anna that you have had to ImmunoGen's story. First question for me is, I just wondered if you can maybe talk a little bit about some of the major differences in ovarian cancer treatment or practice, I guess, in the U.S. versus some of the major countries in the EU. And what impact maybe those differences could have on sort of the launch trajectory or maybe your overall strategy in Europe versus what we've seen early on here in the U.S.? And then I have a follow-up.

偉大的。祝賀本季度，也想表達我的同事對 Anna 對ImmunoGen 故事所做貢獻的看法。我的第一個問題是，我只是想知道您是否可以談談美國與歐盟一些主要國家在卵巢癌治療或實踐方面的一些主要差異。這些差異可能會對發射軌跡或您在歐洲的總體戰略與我們早期在美國看到的情況產生什麼影響？然後我有一個後續行動。

Sure. So I'll start with practice pattern differences and then turn it over to my colleagues to discuss how that influences our launch strategy in Europe. The one real difference, Etzer, is how and when physicians use bevacizumab or Avastin. And we've known that. It was approved in 2014, 2015, it has 3 approvals in the U.S. and Europe. It's approved in combination with chemotherapy in platinum-resistant disease. It's approved in combination with chemotherapy in recurrent platinum-sensitive disease and then continued as maintenance and in the frontline setting in combination with chemotherapy, and as continued as maintenance.

當然。因此，我將從實踐模式差異開始，然後將其交給我的同事，討論這如何影響我們在歐洲的發布策略。 Etzer，真正的區別在於醫生如何以及何時使用貝伐珠單抗或阿瓦斯汀。我們都知道這一點。它於2014年、2015年獲得批准，在美國和歐洲有3個批准。它被批准與化療聯合治療鉑類耐藥疾病。它被批准與化療聯合治療復發性鉑敏感疾病，然後繼續維持治療，在一線環境中與化療聯合治療，然後繼續維持治療。

The problem with Bev is that it's never shown an overall survival advantage in any of these settings, except in a core prognosis high-risk subset in the frontline setting. So these are patients who present with Stage 4 disease or parenchymal metastasis. They have ascites. They're suboptimally debulked. In that subset, the addition of bevacizumab does improve overall survival. So particularly in Europe, oftentimes, bevacizumab is only reimbursed or patients only have access to bevacizumab in that frontline poor risk setting.

Bev 的問題在於，除了一線環境中的核心預後高風險子集外，它從未在任何這些環境中顯示出總體生存優勢。這些患者患有第四期疾病或實質轉移。他們有腹水。他們的減重效果不佳。在該子集中，添加貝伐單抗確實可以改善總體生存率。因此，特別是在歐洲，貝伐單抗通常只能得到報銷，或者患者只能在一線低風險環境中獲得貝伐單抗。

And in fact, that kind of bore out in our SORAYA study where the majority of patients were enrolled in the U.S. -- excuse me, in Europe, and that study had a higher percentage of Stage IV patients than is typically seen in a relapsed or recurrent ovarian cancer study. So because of that, in Europe, a higher percentage of patients in the platinum-resistant setting get single agent chemotherapy, and that's important for how we're thinking about ELAHERE when we get it approved.

事實上，這種情況在我們的SORAYA 研究中得到了證實，其中大多數患者是在美國入組的——對不起，是在歐洲入組的，該研究中IV 期患者的比例高於通常在復發或複發患者中看到的比例。復發性卵巢癌研究。因此，在歐洲，鉑類耐藥環境中接受單藥化療的患者比例較高，這對於我們在 ELAHERE 獲得批准時如何考慮它非常重要。

Yes. And the way this translates through the launch is that the unmet need there is even higher, and the number of patients that will be eligible for ELAHERE is also higher. Our goal, therefore, is to, as mentioned by Mark, it to file by the end of this year, and we are making significant progress towards the launch. First, we are working on our global value share and pricing and payers in Europe tend to value overall survival data. So we feel very confident that, that will give us a strong initial position there.

是的。通過推出，這意味著未滿足的需求甚至更高，並且符合 ELAHERE 資格的患者數量也更多。因此，正如馬克所提到的，我們的目標是在今年年底之前提交文件，並且我們正在朝著發布方向取得重大進展。首先，我們正在研究我們的全球價值份額和定價，歐洲的付款人傾向於重視整體生存數據。因此，我們非常有信心，這將為我們提供強有力的初始地位。

Second, we are really pleased that we have a very solid engagement with KOLs there. As you remember, over 70% of our patients in the clinical trials were enrolled is U.S. So those very strong relationships, we are leveraging that. We will be having two oral presentations at ASCO in Istanbul at the end of September, and we also will have a present at ESMO. So we'll continue to have this one-on-one engagement, and we are also partnering with the community in preparation for the launch. Finally, we are ramping up the team towards preparing for execution, and we feel very confident that we have a successful launch in -- us in the U.S.

其次，我們非常高興與那裡的 KOL 建立了非常牢固的合作關係。如您所知，我們參與臨床試驗的患者中有超過 70% 是在美國註冊的，因此我們正在利用這些非常牢固的關係。我們將於 9 月底在伊斯坦布爾的 ASCO 上進行兩次口頭報告，並且還將在 ESMO 上進行演示。因此，我們將繼續進行這種一對一的互動，並且我們還將與社區合作，為發布做準備。最後，我們正在加強團隊準備執行，我們非常有信心我們在美國成功推出。

Maybe the only other thing to add there, Etzer, is that it's just a very highly concentrated market. So when we do the market research across both the 5 largest markets and expanding that into 16 markets. We see a relatively consistent pattern, which is a small number of centers treat a high percentage of the patients. So when we look at the 5 key markets, for example, 60 odd centers treating 80% of the market. So this is something that we can address with a modest incremental commercial investment and particularly given the data that we have. And as Isabel mentioned, the relationships that we have, we expect a very robust launch there.

也許唯一需要補充的一點是，Etzer，這是一個非常高度集中的市場。因此，當我們對 5 個最大市場進行市場研究並將其擴展到 16 個市場時。我們看到一個相對一致的模式，即少數中心治療高比例的患者。所以當我們看5個關鍵市場時，例如，60多個中心佔據了80%的市場。因此，我們可以通過適度增量商業投資來解決這個問題，特別是考慮到我們擁有的數據。正如伊莎貝爾提到的，我們擁有的關係，我們預計在那裡會有非常強勁的推出。

Great. And then the follow-up was on IMGC936. Sort of the market here is paying a lot of attention to sort of another ADC mechanism, the TROP2 in non-small cell lung cancer. And for sort of the interim analysis that you have maybe in the back half of this year, how you're thinking about what the go/no-go is? Is it going to be on response rate, on duration of response? Is it maybe PFS, if you could maybe provide a little bit of color on how you're thinking about sort of the go-forward strategy on that asset?

偉大的。然後後續是IMGC936。這裡的市場非常關注另一種 ADC 機制，即非小細胞肺癌中的 TROP2。對於今年下半年可能進行的中期分析，您如何考慮什麼是繼續/不繼續？是根據響應率、響應持續時間嗎？是否可能是 PFS，您能否提供一些關於您如何考慮該資產的前進策略的信息？

So IMGC936 is our ADAM9-targeting ADC that ADAM9 is expressed across a broad array of solid tumors, and we prioritize non-small cell lung cancer based on what we saw early in development. And so we have expanded the first stage of a 2-stage design, if you will, to understand the activity of IMGC936 in non-small cell lung cancer. And I think the initial hurdle at there would be just overall response rate or objective response rate in the initial cohort of patients. And at that point, that data would guide further expansion into the second stage, at which point we would have a larger data set where we would look at ORR and DOR to assess how we're thinking about further development.

因此，IMGC936 是我們的 ADAM9 靶向 ADC，ADAM9 在多種實體瘤中表達，我們根據早期發展情況優先考慮非小細胞肺癌。因此，如果您願意的話，我們擴展了兩階段設計的第一階段，以了解 IMGC936 在非小細胞肺癌中的活性。我認為最初的障礙只是初始患者群體的總體緩解率或客觀緩解率。到那時，該數據將指導進一步擴展到第二階段，此時我們將擁有更大的數據集，我們將在其中查看 ORR 和 DOR 來評估我們如何考慮進一步的開發。

Just in terms of single-arm studies and PFS data, typically, it's hard to make robust decisions based on PFS. So it's typically ORR and DOR data that will guide further decision-making.

僅就單臂研究和 PFS 數據而言，通常很難根據 PFS 做出穩健的決策。因此，通常 ORR 和 DOR 數據將指導進一步的決策。

The next question comes from Boris Peaker with Cowen.

下一個問題來自鮑里斯·皮克和考恩。

I'd like to add my congratulations to Anna specifically and the entire ImmunoGen team for the excellent progress. So maybe my first question is on the testing centers. You've obviously mentioned that there's been an increasing in testing centers being brought online. But how much do you estimate maybe the current revenue being potentially limited based on the existing testing infrastructure in the second quarter?

我要特別祝賀 Anna 和整個 ImmunoGen 團隊取得的出色進展。所以也許我的第一個問題是關於測試中心的。您顯然已經提到，越來越多的測試中心上線。但是，根據第二季度現有的測試基礎設施，您估計當前收入可能會受到多少限制？

Yes. Not at all. I mean, we just -- testing is simply not a barrier to entry. We do know that the institutions at present have a preference for in-house testing, but that didn't prevent them from sending tests out to -- so before their centers were open we could see ordering from accounts and testing from accounts that didn't have in-house testing. And as we've mentioned, as time progresses, a number of those institutions are taking it in-house.

是的。一點也不。我的意思是，我們只是——測試根本不是進入的障礙。我們確實知道，這些機構目前更傾向於內部測試，但這並沒有阻止他們將測試發送給——所以在他們的中心開放之前，我們可以看到從賬戶訂購和從沒有測試的賬戶進行測試。沒有內部測試。正如我們所提到的，隨著時間的推移，其中許多機構正在將其納入內部。

What I will also say, Boris, is we've actually had some interesting conversations about this phenomenon as it related to PD-1, PD-L1 testing. And what we hear is, initially, there was great enthusiasm among the academic institutions to take that testing in-house. However, over time, that enthusiasm waned some degree and they began sending their tests back out to centralized labs. So we -- as we've discussed, we see the migration in-house over time, whether that's a sustainable phenomenon I think, is an open question at this point. But just to be very clear, we've done over 13,000 tests launched to date. It has simply not been a barrier to entry.

Boris，我還要說的是，我們實際上就這一現象進行了一些有趣的對話，因為它與 PD-1、PD-L1 測試相關。我們聽到的是，最初，學術機構對內部測試抱有極大的熱情。然而，隨著時間的推移，這種熱情有所減弱，他們開始將測試發送回集中實驗室。因此，正如我們所討論的，隨著時間的推移，我們看到內部遷移，我認為這是否是一種可持續的現象，目前是一個懸而未決的問題。但需要明確的是，迄今為止我們已經進行了超過 13,000 次測試。它根本就不是進入的障礙。

Great. And my second question is in terms of the NCCN guidelines, do you anticipate any future updates incorporating with MIRASOL or any other data in the near future?

偉大的。我的第二個問題是關於 NCCN 指南，您預計在不久的將來會有與 MIRASOL 或任何其他數據合併的未來更新嗎？

Yes. So we anticipate with MIRASOL being the only study to show an overall survival advantage in a randomized Phase III setting for a novel agent. We anticipate MIRASOL could move our ELAHERE compendia listing from 2A to Category 1 and it would be the only medication in the NCCN platinum-resistant treatment guideline that would have that level of evidence. We also are anticipating that the PICCOLO data could support NCCN compendia for later line platinum-sensitive ovarian cancer for MIRV monotherapy. And also, we are generating 3 data sets at this point for mirvetuximab plus carboplatin, the 420 study that is our sponsored study in low, medium and high FR alpha expressing patients as well as we are supporting 2 investigator-sponsored trials, neoadjuvant study and a randomized Phase II study in Germany led by Philip Harter and those data could absolutely support compendia listing as well.

是的。因此，我們預計 MIRASOL 是唯一一項在隨機 III 期環境中顯示新型藥物具有總體生存優勢的研究。我們預計 MIRASOL 可以將我們的 ELAHERE 藥典清單從 2A 轉移到 1 類，並且它將是 NCCN 鉑類耐藥治療指南中唯一具有該級別證據的藥物。我們還預計 PICCOLO 數據可以支持 NCCN 概要，用於 MIRV 單藥治療的後期鉑敏感卵巢癌。此外，我們目前正在為mirvetuximab 加卡鉑生成3 個數據集，這項420 研究是我們贊助的針對低、中和高FR α 表達患者的研究，並且我們正在支持2 項研究者贊助的試驗、新輔助研究和由 Philip Harter 領導的德國一項隨機 II 期研究，這些數據也絕對可以支持藥典列出。

Yes. We also hope that we can move -- sorry, the compendia listing of the combination from 2B to 2A for MIRV BEV.

是的。我們還希望我們能夠將 MIRV BEV 的組合從 2B 更改為 2A 的概要列表。

Do you have a sense of timing for that?

你對此有把握嗎？

Well, we are aiming to make some changes for the listing of ELAHERE monotherapy in October and similarly for the combination of MIRV BEV from 2b to 2A.

嗯，我們的目標是對 10 月份上市的 ELAHERE 單藥療法做出一些改變，同樣對 MIRV BEV 的組合從 2b 到 2A 進行一些改變。

Yes, we will work with NCCN around their scheduled meetings.

是的，我們將與 NCCN 圍繞他們安排的會議進行合作。

Congratulations once again.

再次祝賀。

The next question comes from Andy Hsieh with William Blair.

下一個問題來自安迪·謝和威廉·布萊爾。

Congrats on the another full out quarter and it's bit of pleasure working with you, Anna. I wish you the best of luck. So I have a question about kind of the strength of the community in nonacademic centers. So I'm curious if you have a view on that or any sort of market dynamics you're seeing there? And I also have a follow-up in terms of the R&D and your P&L. Obviously, strength from ELAHERE could fuel your R&D. I'm just curious about maybe the near- and midterm vision about R&D, what's in store, what do you expect the R&D to look like in the next 3 years? In terms of P&L. Obviously, you're pretty close to breakeven this quarter. I'm just curious if that's the goal. How do you think about your income statement as ELAHERE continues to ramp at this just incredible pace?

祝賀又一個完整的季度，很高興與您合作，安娜。祝你好運。所以我有一個關於非學術中心社區的力量的問題。所以我很好奇您對此或您在那裡看到的任何市場動態有何看法？我還有研發和損益方面的後續行動。顯然，ELAHERE 的實力可以為您的研發提供動力。我只是好奇研發的近期和中期願景，即將發生什麼，您預計未來三年的研發會是什麼樣子？就損益而言。顯然，本季度您已經非常接近收支平衡。我只是好奇這是否是目標。隨著 ELAHERE 繼續以令人難以置信的速度增長，您如何看待您的損益表？

Sure. Thanks, Andy. So I'm going to ask Isabel to start, and then Mike to talk about R&D and then some combination of Renee and I can tackle the P&L.

當然。謝謝，安迪。所以我要請伊莎貝爾開始，然後邁克談談研發，然後蕾妮和我的一些組合可以解決損益問題。

Sure. So we are very pleased with the strong adoption in both the community and academic centers. And if you remember early in the launch, we thought that the academic centers will start at first and community with fall. What we have seen is a very strong adoption in community and that's a testament to the unmet need and the target profile of the drug. We also see that academics have to follow the normal process. They have to wait for the (inaudible) committees. They have to wait for hub in some centers, they test in in-house but they have now starting to test, and we are very pleased that pretty much all the major institutions are already ordered ELAHERE.

當然。因此，我們對社區和學術中心的大力採用感到非常高興。如果您還記得在啟動之初，我們認為學術中心將首先啟動，社區將在秋季啟動。我們所看到的是社區中非常廣泛的採用，這證明了該藥物的未滿足需求和目標概況。我們也看到學術界必須遵循正常的流程。他們必須等待（聽不清）委員會的到來。他們必須等待一些中心的中心，他們在內部進行測試，但他們現在已經開始測試，我們很高興幾乎所有主要機構都已經訂購了 ELAHERE。

We have additional events that will create additional growth in both. We have the J code since July 1. We have been included in pathways. And we think that, that's going to continue driving the growth in both academic and nonacademic institutions. In terms of the mix, we think it will remain relatively similar with more 65% to 35% with more growth maybe coming from academic institutions in the second quarter.

我們還有其他活動將在這兩個方面帶來額外的增長。我們從 7 月 1 日起就有 J 代碼。我們已被納入途徑。我們認為，這將繼續推動學術和非學術機構的增長。就結構而言，我們認為第二季度將保持相對相似，即 65% 至 35% 左右，更多增長可能來自學術機構。

And Andy, this is Mike. Regarding your question about continued investment in R&D, just to remind you, and it's nicely summarized, we have a broad ongoing life cycle management program with mirvetuximab. It's important for us to think about every woman with ovarian cancer that express folate receptor alpha to have the right medicine at the right time that will include investigation of ELAHERE in platinum-sensitive ovarian cancer. You already heard about that, but I wanted to also remind you about IMGN151, which we continue to move through Phase I development. And has the potential to broadly impact FR alpha expressing cancers, not only in ovarian cancer, but beyond in cancer, such as endometrial, nonsmall cell lung cancer and others. You've also heard about the continued investment of PVEK in frontline AML, and we look forward to those data informing continued clinical development there.

安迪，這是邁克。關於您關於持續投資研發的問題，只是提醒您，並且總結得很好，我們有一個廣泛的、持續的 mirvetuximab 生命週期管理計劃。對於我們來說，重要的是要考慮到每一位患有表達葉酸受體 α 的卵巢癌的女性在正確的時間使用正確的藥物，其中包括對 ELAHERE 在鉑敏感卵巢癌中的研究。您已經聽說過這一點，但我還想提醒您有關 IMGN151，我們將繼續進行第一階段的開發。並且有可能廣泛影響表達 FR α 的癌症，不僅限於卵巢癌，還包括子宮內膜癌、非小細胞肺癌等其他癌症。您還聽說過 PVEK 在一線 AML 方面的持續投資，我們期待這些數據為該領域的持續臨床開發提供信息。

And then importantly, as a reminder, we have 3 broad classes of payloads with associated linkers that form the basis of our portfolio, by the maytansinoids, the IGN and importantly, a camptothecin group of compounds that have yet to be formally tested in clinical development. So we look forward to work that's already ongoing with collaborators to link forward novel antibodies, linkers and test those payloads in a broad swath of cancers. So we're really very committed across the spectrum and look forward to sharing this earlier, progress of molecules and research as we move forward closer to IND.

然後重要的是，提醒一下，我們有3 類廣泛的有效負載以及相關的連接器，它們構成了我們產品組合的基礎，其中包括美登木素生物鹼、IGN 以及重要的是尚未在臨床開發中進行正式測試的喜樹鹼化合物組。因此，我們期待著與合作者正在進行的工作，以連接新型抗體、接頭，並在廣泛的癌症中測試這些有效負載。因此，我們確實非常致力於整個領域，並期待在我們接近 IND 時分享分子和研究的早期進展。

So Andy, as Mike just articulated and we've also talked about the expansion globally of ELAHERE with the labeled indications. We do expect to invest heavily in the business in the coming years. So we've given cash guidance to say that we've got more than 2 years' worth of cash, and that is a reflection of both the existing balance sheet as well as the strength of the ELAHERE here launch. But we aspire to be a fully integrated oncology company. We're fortunate to have one marketed product and 3 additional clinical candidates. But our goal is, again, to expand our preclinical capabilities.

安迪，正如邁克剛才所闡述的那樣，我們還討論了 ELAHERE 的全球擴張以及標籤適應症。我們確實希望在未來幾年對該業務進行大量投資。因此，我們給出的現金指導表明，我們擁有超過 2 年的現金價值，這既反映了現有的資產負債表，也反映了 ELAHERE 在這裡推出的實力。但我們渴望成為一家完全一體化的腫瘤學公司。我們很幸運擁有一種已上市產品和另外 3 種臨床候選產品。但我們的目標還是擴大我們的臨床前能力。

We've done so incrementally with a number of partnerships, and we look to continue that activity and also rebuild some in-house capabilities as it relates to our core areas of expertise, as Mike has outlined. So the focus is, again, international expansion for the business, supporting the launch life cycle management and rebuilding our preclinical pipeline. So again, areas of investment on a go-forward basis.

正如邁克所概述的，我們已經通過許多合作夥伴逐步做到了這一點，我們希望繼續這項活動，並重建一些與我們的核心專業領域相關的內部能力。因此，重點再次是業務的國際擴張，支持啟動生命週期管理並重建我們的臨床前管道。再次強調，投資領域是前瞻性的。

The next question comes from Kelly Shi with Jefferies.

下一個問題來自 Jefferies 的 Kelly Shi。

Congrats for another great quarter, and also please allow me to add my congrats to Anna. My first question is for PICCOLO trial, what kind of treatment duration could we expect and also in this platinum-sensitive setting is the proportion of FR alpha high patients (inaudible) as in the platinum-resistant settings around 35% to 40%?

祝賀又一個偉大的季度，也請允許我向安娜表示祝賀。我的第一個問題是，對於PICCOLO 試驗，我們可以預期什麼樣的治療持續時間，以及在鉑類敏感的環境中，FR α 高患者的比例（聽不清），與鉑類耐藥環境中的比例約為35% 至40%？

Thanks, Kelly. So let me address your second question first. The vast majority of patients who have participated in mirvetuximab trials and who are receiving commercial ELAHERE do so based on archival tumor tissue testing. So patients generally have debulking surgery at the time of diagnosis, and that's when they're for alpha. That's when they have tumor taken for FR alpha testing. So the 35% to 40% is true regardless of what setting the patient is in.

謝謝，凱利。那麼讓我先回答你的第二個問題。絕大多數參加了 mirvetuximab 試驗並接受商業 ELAHERE 治療的患者都是根據檔案腫瘤組織檢測進行試驗的。因此，患者通常在診斷時就進行減瘤手術，那時他們就需要接受阿爾法治療。那時他們會取出腫瘤進行 FR α 測試。因此，無論患者處於何種環境，35% 到 40% 都是正確的。

Going back to your first question about treatment duration for PICCOLO, these are later line platinum-sensitive patients, but we know that platinum-sensitive patients in general do better than platinum-resistant patients regardless of therapy, although again, that does seem to be possibly changing for the subset of platinum-sensitive patients post-PARP who get more platinum. That said, we anticipate the treatment duration for the PICCOLO study is going to be appreciably longer than, for example, in MIRASOL or SORAYA. So stay tuned.

回到關於PICCOLO 治療持續時間的第一個問題，這些是後期鉑類敏感患者，但我們知道，無論治療如何，鉑類敏感患者總體上比鉑類耐藥患者效果更好，儘管同樣，這似乎確實是可能會改變 PARP 後鉑類敏感患者接受更多鉑類藥物的情況。也就是說，我們預計 PICCOLO 研究的治療持續時間將明顯長於 MIRASOL 或 SORAYA 等研究的治療持續時間。所以請繼續關注。

Okay. Great. And also, for 936 in non-small cell lung cancer cohort. Just curious, is this precise by the interim analysis applied to post the P1 setting?

好的。偉大的。此外，還有 936 名非小細胞肺癌患者。只是好奇，用於發布 P1 設置的臨時分析是否準確？

So it's not specifically in the post-PD-1 setting but this is a Phase I study where patients with non-small cell lung cancer have had the appropriate prior therapies and the vast majority, if not all of them have had a checkpoint inhibitor.

因此，這並不是專門針對PD-1 治療後的情況，而是一項I 期研究，其中非小細胞肺癌患者已經接受過適當的先前治療，並且絕大多數（如果不是全部）都接受過檢查點抑製劑。

The next question comes from RK with H.C. Wainright.

下一個問題來自 RK 和 H.C.溫賴特。

Anna, congratulations and nothing like signing off on a high note. I will certainly miss you, especially on all the helpful conversations that we have had in the last few years. And additionally, both my dog and I'm going to miss you on our Zoom calls, future Zoom calls with ImmunoGen. So in terms of expectations that the ESGO what additional analysis could we see at that conference?

安娜，恭喜你，沒有什麼比高調結束更好的了。我肯定會想念你，尤其是過去幾年我們進行的所有有益的對話。此外，我和我的狗都會在我們的 Zoom 通話中想念您，以及未來與 ImmunoGen 進行的 Zoom 通話。那麼，就 ESGO 的期望而言，我們能在這次會議上看到哪些額外的分析呢？

Yes. ESGO is in Istanbul this fall. I think it's the end of September. And we have 2 abstracts that have been accepted for oral presentation in terms of additional subset analyses from MIRASOL. The ones that we'll be focused on in this initial -- are the subsets based on a number of prior lines of therapy as well as patients who have or have not had a prior PARP inhibitor. So those are the key subsets because physicians are quite interested to understand where to position ELAHERE in the treatment paradigm. And I think these subset data will be very informative for them.

是的。 ESGO 今年秋天將在伊斯坦布爾舉行。我認為這是九月底。我們有 2 篇摘要已被接受用於 MIRASOL 額外子集分析的口頭報告。我們將在本文中重點關注的是基於多種先前治療方案以及先前使用過或未使用過 PARP 抑製劑的患者的子集。因此，這些是關鍵的子集，因為醫生非常有興趣了解 ELAHERE 在治療範式中的定位。我認為這些子集數據將為他們提供非常豐富的信息。

Also, as you plan to file the MAA in Europe during the next 6 months, what -- how should we think about the commercialization there? Would this be directly by yourselves? Or would you -- or you're seeking for the commercial partner there? I'm just trying to understand the commercial structure that could be set up in it.

另外，由於您計劃在未來 6 個月內在歐洲提交 MAA，我們應該如何考慮在那裡的商業化？這會是你自己直接做的嗎？或者您會——或者您正在那裡尋找商業合作夥伴？我只是想了解其中可以建立的商業結構。

Sure, RK. So we plan to go direct in the 5 largest markets and there's a pretty leveraged approach that one can take by clustering so we can add 11 additional markets. So we expect to be direct in 16 markets in Europe. Of course, that takes place over time, just given the cadence of reimbursement in those markets. And then we would use distributors outside of the -- what we call the EU16.

當然，RK。因此，我們計劃直接進入 5 個最大的市場，並且可以通過集群採取一種非常有效的方法，這樣我們就可以添加 11 個額外的市場。因此我們預計將直接進入歐洲 16 個市場。當然，考慮到這些市場的報銷節奏，這種情況會隨著時間的推移而發生。然後我們會使用我們所說的歐盟 16 國以外的分銷商。

The next question comes from Asthika Goonewardene with Truist.

下一個問題來自 Asthika Goonewardene 和 Truist。

Asthika from Truist here. I'm going to also offer my congratulations on very elegant execution to the team and on a personal note to Anna, we only launched coverage 9 months ago, but in a limited time, it's been a pleasure to get to know you and appreciate your discipline. We wish you the best for your next adventure. Just a couple of quick mop-up questions for us here. You're clearly getting a nice boost from what one might call off-label use in the U.S. But in general, in oncology, do you think off-label use in Europe can be as strong as you do get in the U.S.? Or do you think the doctor there in Europe are going to stick to the script a bit more?

來自 Truist 的 Asthika。我還要向團隊的出色執行表示祝賀，並向安娜表示個人的祝賀，我們在 9 個月前才推出報導，但在有限的時間內，很高興認識您並感謝您的支持。紀律。我們祝您下次冒險一切順利。這裡只是向我們提出幾個快速清理問題。顯然，您從美國所謂的超適應症使用中得到了很好的推動。但總的來說，在腫瘤學領域，您認為歐洲的超適應症使用會像在美國一樣強勁嗎？或者你認為歐洲的醫生會更堅持劇本嗎？

Second question is I'd like to test and see if I can get any sort of color on time lines for GLORIOSA? I know that's one of the next things that people are going to be looking at as well here, after PICCOLO. And then lastly, Mark, when do you feel confident that you'll get enough example from the claims data to give us some guidance on a product level basis in ELAHERE.

第二個問題是我想測試一下是否可以在 GLORIOSA 的時間線上獲得任何顏色？我知道，繼 PICCOLO 之後，這也是人們接下來會關注的事情之一。最後，馬克，您什麼時候有信心從索賠數據中獲得足夠的示例，以便為我們提供有關 ELAHERE 產品級別的一些指導。

As to the first question, it's not so much the physicians that make the decisions with respect to the use outside the label in Europe is just the reimbursement there. And it's very stringent. There are very limited instances where you can see off-label coverage there, and that's distinct from what we see in the U.S. market, particularly where drugs are listed in the compendia, as we've seen with ELAHERE both in terms of no restriction on prior lines of therapy and the combination with Avastin.

關於第一個問題，在歐洲，決定是否在標籤外使用的決定因素並不是醫生，而是那裡的報銷。而且非常嚴格。在那裡您可以看到標籤外覆蓋的情況非常有限，這與我們在美國市場上看到的情況不同，特別是在藥典中列出的藥物，正如我們在ELAHERE 上看到的那樣，兩者都沒有限制先前的治療方案以及與阿瓦斯汀的聯合治療。

So it's -- they are fundamentally different markets as it relates to reimbursement, and that's what drives it. So the expectation should be -- the use there will be within the label approved by the EMA. In terms of GLORIOSA, it's early days, so we haven't given any guidance there. And then sorry, your third question was?

所以它們是根本不同的市場，因為它與報銷有關，這就是推動它的原因。因此，預期應該是——使用將在 EMA 批准的標籤範圍內。就嘉蘭而言，現在還處於早期階段，所以我們還沒有給出任何指導。抱歉，你的第三個問題是？

Yes, yes. I think it needs to be driven by 2 things, the 2 key factors that are most opaque at this point are duration of therapy and really importantly, discontinuations, which of course, are related to duration of therapy. And I think it's going to be some time before we get to that. I certainly would expect us by the beginning of next year when we all get together at JPMorgan or in conjunction with our year-end earnings call to have a reasonably clear eye view on that. And as I say, we've got this demand study going, and we'll see what that tells us as well.

是的是的。我認為它需要由兩件事驅動，目前最不透明的兩個關鍵因素是治療持續時間，以及非常重要的停藥，這當然與治療持續時間有關。我認為我們還需要一段時間才能做到這一點。我當然希望我們在明年初在摩根大通聚會時或在年終財報電話會議上對此有一個相當清晰的看法。正如我所說，我們正在進行這項需求研究，我們也會看看它能告訴我們什麼。

The next question comes from Joe Catanzaro with Piper Sandler.

下一個問題來自 Joe Catanzaro 和 Piper Sandler。

Congrats on the nice quarter. Congrats to you, Anna, on a nice tenure here. Maybe just 2 for me. I'm wondering if you had a sense around the cadence of new patient starts in 2Q and whether it was evenly distributed not and relatedly, whether you saw an uptick in usage in June and July following the MIRASOL presentation at ASCO. And then my second question, Mark, you mentioned sort of the difficulty in modeling prevalent to incidents. I'm wondering sort of where you think you are in that curve and what metrics you're looking at that will give you an indication that you're shifting to majority usage in the incident population?

祝賀這個美好的季度。安娜，祝賀你在這裡度過了愉快的任期。也許對我來說只有2個。我想知道您是否對第二季度新患者啟動的節奏有一定的了解，是否分佈均勻，相關的，在 ASCO 上 MIRASOL 演示之後，您是否看到 6 月和 7 月的使用量有所上升。然後我的第二個問題，馬克，你提到了對事件普遍存在的建模困難。我想知道您認為自己處於該曲線的哪個位置，以及您正在查看哪些指標可以表明您正在轉向事件人群中的大多數使用？

Okay. So when it comes to the incidents versus prevalent population and how we are looking at the patient data, we have a longitudinal data and claims. The issue with that, frankly, is that is lagging 90 days. So we have very few patient data at this point. We get it from DRG by lines of therapy. And we are tracking that, and we think we'll need additional time before we can tell you what is happening there.

好的。因此，當涉及到事件與流行人群以及我們如何看待患者數據時，我們有縱向數據和聲明。坦率地說，問題是滯後了 90 天。所以目前我們的患者數據非常少。我們通過一系列治療從 DRG 獲得它。我們正在跟踪這一情況，我們認為我們需要更多時間才能告訴您那裡發生了什麼。

We had seen though that the MIRASOL data does have an impact in terms of uptake of more patients, as you saw in the second quarter. And we also can see early signs from the claims that patients are moving to treat in earlier lines of therapy pretty much as a science of first resistance.

但我們已經看到，MIRASOL 數據確實對更多患者的接受產生了影響，正如您在第二季度看到的那樣。我們還可以從患者正在轉向早期治療的說法中看到早期跡象，這幾乎就像一門首次耐藥的科學。

The next question is from Jonathan Chang with Leerink Partners.

下一個問題來自 Leerink Partners 的 Jonathan Chang。

Congrats on the quarter and best wishes Anna on next steps. Just one question for me. How are you guys thinking about potential business development opportunities for ELAHERE and strategic interest broadly?

祝賀本季度，並祝愿安娜下一步順利。只是問我一個問題。你們如何看待 ELAHERE 的潛在業務發展機會和廣泛的戰略利益？

Yes. So what we've done with ELAHERE is we've decided to go direct in the largest markets where we can with modest investment support a robust launch. So starting here in the U.S., as we have talked a bit on this call, going to Europe, in markets where that's not feasible for example, in China, we've elected to go with partners. We're exploring partnerships for Japan in a similar vein. And outside of that, I think we plan to use distributors because we think that with the time limited distribution agreement, we can call back those when we're ready to move to a direct model.

是的。因此，我們對 ELAHERE 所做的就是決定直接進入最大的市場，在那裡我們可以通過適度的投資支持強勁的發布。因此，從美國開始，正如我們在這次電話會議上談到的那樣，到歐洲，在那些不可行的市場，例如在中國，我們選擇與合作夥伴一起去。我們正在以類似的方式探索與日本的合作夥伴關係。除此之外，我認為我們計劃使用分銷商，因為我們認為，通過有時間限制的分銷協議，當我們準備好轉向直接模式時，我們可以收回這些分銷商。

So in terms of more broadly business development, as we've talked, we want to rebuild the front end of the pipeline and some of the deals that we've done, OBT and more recently, a very small deal with ImmunoBiochem, again to build the front end of the pipeline. So we're very excited about this business. We love the momentum that's been generated this quarter in the marketplace, and that's paired very nicely with data progress with the pipeline. So we're excited about our long-term prospects here.

因此，就更廣泛的業務發展而言，正如我們所說，我們希望重建管道的前端以及我們已經完成的一些交易，OBT 以及最近與ImmunoBiochem 的一項非常小的交易，再次是為了構建管道的前端。所以我們對這項業務感到非常興奮。我們喜歡本季度市場產生的勢頭，這與管道的數據進展非常匹配。因此，我們對這裡的長期前景感到興奮。

I show no further questions at this time. I would now like to turn the call back to Mark for closing remarks.

我目前沒有提出任何進一步的問題。現在我想將電話轉回給馬克，讓他發表結束語。

Great. Well, thank you all very much for joining us today. We had a very strong first half. We do expect to carry this momentum for the remainder of the year as we look to deliver more good days for our patients and importantly, create value for our shareholders. So we look forward to keeping you updated on our progress as we move through the second half. So thanks again for your time today.

偉大的。非常感謝大家今天加入我們。我們上半場表現非常強勁。我們確實希望在今年剩餘時間內保持這種勢頭，因為我們希望為我們的患者帶來更多美好的日子，更重要的是，為我們的股東創造價值。因此，我們期待在下半年向您通報我們的最新進展。再次感謝您今天抽出時間。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。