Blueprint Medicines Corp (BPMC) 2023 Q1 法說會逐字稿

Good morning. My name is Kelly, and I will be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicines First Quarter 2023 Financial Results Conference Call. (Operator Instructions) Jenna Cohen, please begin.

早上好。我叫凱利，今天我將擔任你們的會議操作員。現在，我歡迎大家參加 Blueprint Medicines 2023 年第一季度財務業績電話會議。 （操作員指示）Jenna Cohen，請開始。

Thank you, and good morning, everyone. Welcome to the Blueprint Medicines First Quarter 2023 Financial and Operating Results Conference Call.

謝謝大家，大家早上好。歡迎參加 Blueprint Medicines 2023 年第一季度財務和運營業績電話會議。

This morning, we issued a press release, which outlines the topics we plan to discuss today. You can access the press release as well as the slides that we'll be reviewing by going to the Investors section of our website at www.blueprintmedicines.com.

今天早上，我們發布了一份新聞稿，概述了我們今天計劃討論的主題。您可以訪問我們網站 www.blueprintmedicines.com 的投資者部分，訪問新聞稿以及我們將審閱的幻燈片。

Joining today with prepared remarks are Kate Haviland, Chief Executive Officer; Philina Lee, Chief Commercial Officer; Becker Hewes, Chief Medical Officer; and Mike Landsittel, Chief Financial Officer. Fouad Namouni, President of Research and Development; and Christy Rossi, Chief Operating Officer, are also joining our call and will be available for Q&A.

今天，首席執行官凱特·哈維蘭 (Kate Haviland) 發表了事先準備好的講話； Philina Lee，首席商務官；貝克·休斯 (Becker Hewes)，首席醫療官；和首席財務官 Mike Landsittel。 Fouad Namouni，研發總裁；首席運營官克里斯蒂·羅西 (Christy Rossi) 也將加入我們的電話會議並接受問答。

Before we begin, I'd like to remind you that some of the statements made during the call today are forward-looking statements and are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in our reports filed with the SEC.

在我們開始之前，我想提醒您，今天電話會議中所做的一些陳述屬於前瞻性陳述，並受到許多風險和不確定性的影響，這些風險和不確定性可能導致我們的實際結果出現重大差異，包括中所述的風險和不確定性。我們向美國證券交易委員會提交的報告。

I'll now hand the call over to Kate.

我現在將電話轉給凱特。

Thanks, Jenna, and good morning, everyone. Last year, we introduced our 2027 blueprint, a 5-year growth strategy to achieve what we call precision at scale.

謝謝，珍娜，大家早上好。去年，我們推出了 2027 年藍圖，這是一項五年增長戰略，旨在實現我們所說的大規模精準化。

What lies at the heart of that vision is our ability to scale our business operations as we execute on commercial launches, advance our clinical programs and bring even more innovative compounds into the clinic. Our progress in the first quarter of 2023 has certainly shown that we are driving performance and are poised to deliver tremendous value in the years ahead.

這一願景的核心是我們在執行商業上市、推進臨床項目並將更多創新化合物引入臨床時擴大業務運營的能力。我們在 2023 年第一季度取得的進展無疑表明我們正在推動業績增長，並準備在未來幾年創造巨大的價值。

First, we delivered strong commercial performance in Q1. We achieved $39.1 million in AYVAKIT net product revenue for the quarter, driven by growth in demand as well as by strong execution that resulted in favorable dynamics into proportion of patients on commercial drug.

首先，我們在第一季度取得了強勁的商業業績。在需求增長以及強有力的執行力的推動下，本季度我們的 AYVAKIT 產品淨收入達到了 3910 萬美元，這導致使用商業藥物的患者比例出現了有利的變化。

In a moment, Philina will discuss in more detail our continued success in driving AYVAKIT uptake in advances. Second, we continue to advance our pipeline. We are resuming the VELA trial of BLU-222 after working with the FDA to expeditiously resolve a partial clinical hold within weeks.

稍後，Philina 將更詳細地討論我們在推動 AYVAKIT 的普及方面持續取得的成功。其次，我們繼續推進我們的管道。在與 FDA 合作以在幾週內迅速解決部分臨床擱置問題後，我們將恢復 BLU-222 的 VELA 試驗。

Our team's fast progress in coordination with the FDA emphasize how well we collaborate with regulatory agencies in the face of an ever-evolving regulatory landscape and the urgency with which we are working to bring our investigational medicines to patients in need.

我們的團隊與 FDA 協調的快速進展強調了我們在面對不斷變化的監管環境時與監管機構的合作程度，以及我們努力將我們的研究藥物帶給有需要的患者的緊迫性。

Third, we advanced toward key data inflection points for our best-in-class innovative investigational medicines. We announced that next month at ASCO, we will present dose escalation data across 3 of our development programs. Becker will share more about what you can expect at ASCO later on the call.

第三，我們朝著一流的創新研究藥物的關鍵數據拐點邁進。我們宣布，下個月在 ASCO 上，我們將展示我們 3 個開發項目的劑量遞增數據。貝克爾將在稍後的電話會議上分享更多有關 ASCO 的信息。

Blueprint is distinguished by having a breadth of new product opportunities across our pipeline, while at the same time, we are heading into a major commercial launch with the expansion of our AYVAKIT label. We are now a couple of weeks out from our PDUFA date for AYVAKIT in indolent SM. Our field teams are in the market delivering on prelaunch activities and are ready to support health care providers and patients upon approval. This approval will further solidify Blueprint's leadership in SM.

Blueprint 的特點是在我們的產品線中擁有廣泛的新產品機會，同時，隨著我們的 AYVAKIT 標籤的擴展，我們正在進入一項重大的商業發布。現在距離惰性 SM 中 AYVAKIT 的 PDUFA 日期還有幾週時間。我們的現場團隊正在市場上開展啟動前活動，並準備在獲得批准後為醫療保健提供者和患者提供支持。此次批准將進一步鞏固 Blueprint 在 SM 領域的領導地位。

As the cornerstone of our SM franchise, AYVAKIT establishes the bar as both the first and best-in-class therapy for ISM, enabling our team to accelerate the realization of what we are confident will be a greater than $1.5 billion market opportunity. Now let me turn it over to Philina to discuss our commercial progress with AYVAKIT and the confidence we have in our go-to-market execution. Philina?

作為我們 SM 特許經營權的基石，AYVAKIT 確立了 ISM 首個也是同類最佳療法的標準，使我們的團隊能夠加速實現我們相信將超過 15 億美元的市場機會。現在讓我把它交給 Philina，討論我們與 AYVAKIT 的商業進展以及我們對上市執行的信心。菲莉娜？

Thanks, Kate. Good morning, everyone. We had a strong first quarter, generating AYVAKIT net product revenue of $39.1 million, including $34.9 million in the U.S. Let's look at the key sources of revenue growth in more detail. Half of this growth was due to greater demand and strength across several fundamentals in our AYVAKIT base business.

謝謝，凱特。大家，早安。我們第一季度表現強勁，AYVAKIT 產品淨收入為 3910 萬美元，其中美國收入為 3490 萬美元。讓我們更詳細地看看收入增長的主要來源。這一增長的一半歸因於我們 AYVAKIT 基礎業務的多個基本面的更大需求和實力。

We grew the number of patients on therapy, exiting the quarter with approximately 520 patients on AYVAKIT in the U.S. We added over 70 new accounts increasing the breadth of prescribing to nearly 460 accounts with AYVAKIT experience, and we continue to capture more than 75% of new patient starts and switches.

我們增加了接受治療的患者數量，本季度美國有約 520 名患者接受 AYVAKIT 治療。我們增加了 70 多個新賬戶，將處方範圍擴大到近 460 個擁有 AYVAKIT 經驗的賬戶，並且我們繼續獲得超過 75% 的客戶新病人開始並切換。

The remaining half of this growth we saw this quarter was driven by a reduction in the percent of patients on free drug as some patients were instead able to receive AYVAKIT commercially. We expect this benefit to be temporary and the proportion of patients on free drug to return to more typical levels by the end of Q2.

我們本季度看到的增長的剩餘一半是由免費藥物患者百分比的減少推動的，因為一些患者能夠接受商業 AYVAKIT。我們預計這種好處是暫時的，接受免費藥物的患者比例將在第二季度末恢復到更典型的水平。

We've also completed the hiring and training of our expanded field team members who have been activated and engaged in customers since the end of the quarter. With the full force of our highly experienced team in place, we expect to drive continued growth in advanced SM, and we are ready for ISM. The year is off to a strong start, giving us great momentum as we head into the ISM launch.

我們還完成了對擴大的現場團隊成員的招聘和培訓，這些團隊成員自本季度末以來已被激活並與客戶互動。憑藉我們經驗豐富的團隊的全部力量，我們期望推動先進 SM 的持續增長，並為 ISM 做好準備。今年有一個良好的開端，為我們邁向 ISM 的推出提供了巨大的動力。

We have never been so ready to unlock the opportunity and deliver for many more patients living with SM. Let's look to that next. We are just 18 days from our PDUFA date in ISM and the energy at Blueprint Medicines is electric. Our team is ready, the market is ready and patients are waiting for AYVAKIT.

我們從未如此準備好釋放機會，為更多 SM 患者提供服務。接下來讓我們看一下。距離 ISM 的 PDUFA 日期僅剩 18 天，Blueprint Medicines 的能源是電力。我們的團隊已準備就緒，市場已準備就緒，患者正在等待 AYVAKIT。

We have shared previously the 3 pillars of our launch strategy: Health care provider engagement, patient activation and patient access. We have consolidated our ISM launch preparations across each of these 3 areas. First, provider engagement. Among Heme/Oncs and allergist/immunologists managing patients with ISM we have grown unaided awareness of AYVAKIT to approximately 40% or double what you would expect from industry benchmarks.

我們之前已經分享過我們推出戰略的三大支柱：醫療保健提供者參與、患者激活和患者訪問。我們已經在這三個領域整合了 ISM 啟動準備工作。首先，提供者的參與。在管理 ISM 患者的 Heme/Oncs 和過敏症專家/免疫學家中，我們已將 AYVAKIT 的獨立認知度提高到大約 40%，即您對行業基準的預期的兩倍。

Our field teams have profiled and built relationships with hundreds of high-volume health care providers to identify patients in need who are most likely to initiate AYVAKIT.

我們的現場團隊已經與數百家大容量醫療保健提供者進行了分析並建立了關係，以確定最有可能啟動 AYVAKIT 的有需要的患者。

Second, patient activation. It's something our unbranded disease awareness campaign is drawing thousands of people who are signed up to receive more information about SM and AYVAKIT upon approval. And third, access. Our patient support program, Your Blueprint, continues to secure industry-leading times to fill and the 25 mg dosage strength is already in the channel with broad payer coverage.

第二，患者激活。我們的無品牌疾病意識活動吸引了數千人報名，以便在獲得批准後獲得有關 SM 和 AYVAKIT 的更多信息。第三，訪問。我們的患者支持計劃“您的藍圖”繼續確保行業領先的填補時間，並且 25 毫克劑量強度已經進入廣泛付款人覆蓋的渠道。

These 3 strategic pillars also frame the performance metrics that we'll focus on to frame our launch progress post approval. For provider engagement and patient activation, our goal is to drive to a decision to treat with AYVAKIT.

這三個戰略支柱還構建了我們將重點關注的績效指標，以框架批准後的發布進度。對於提供者參與和患者激活，我們的目標是推動做出使用 AYVAKIT 治療的決定。

And to measure our progress, we'll look at prescriber breadth particularly in allergist/immunologists as well as growth in the number of patients in therapy. In a chronic disease like ISM, growth in patients on therapy is an important lead indicator of continued revenue growth.

為了衡量我們的進展，我們將關注處方醫生的廣度，特別是過敏科醫生/免疫科醫生，以及接受治療的患者數量的增長。對於 ISM 這樣的慢性疾病，接受治療的患者數量的增長是收入持續增長的重要先行指標。

We'll also be looking to maintain strong patient access for AYVAKIT and will track payer coverage relative to label through the ISM launch. As I shared with our team at our national field meeting last month, the SM story is a Blueprint story. We are the pioneers. The opportunity is there, and we're ready to deliver for patients.

我們還將尋求保持 AYVAKIT 的強大患者訪問權限，並將通過 ISM 發布跟踪與標籤相關的付款人覆蓋範圍。正如我上個月在全國現場會議上與我們的團隊分享的那樣，SM 故事是一個藍圖故事。我們是先鋒。機會就在那裡，我們已準備好為患者提供服務。

We have the right medicine, the right team, and we are ready to launch. And with that, I'll hand it over to Becker, who will share progress across our burgeoning portfolio as we prepare for ASCO.

我們有正確的藥物、正確的團隊，我們已準備好推出。接下來，我將把它交給 Becker，他將在我們為 ASCO 做準備時分享我們不斷發展的產品組合的進展情況。

Thanks, Philina, and good morning, everyone. Blueprint has an exciting pipeline of potential first-in-class and best-in-class therapies targeting CDK2, EGFR and other key targets. We operate on the premise that if the preclinical profiles of our compounds are borne out in the clinic, multiple Blueprint Medicines could become future cornerstones of treatment. We continue to make progress towards that goal. And last week, we announced the acceptance of data presentations at ASCO that will provide an update on dose escalation as we work towards defining recommended doses across 3 of our Phase I/II programs.

謝謝菲莉娜，大家早上好。 Blueprint 擁有一系列令人興奮的潛在一流和一流療法，針對 CDK2、EGFR 和其他關鍵靶點。我們的運作前提是，如果我們化合物的臨床前特徵在臨床中得到證實，多種藍圖藥物可能成為未來治療的基石。我們繼續朝著這一目標取得進展。上週，我們宣布接受 ASCO 上的數據演示，該數據演示將提供有關劑量遞增的最新信息，因為我們致力於確定 3 個 I/II 期項目的推薦劑量。

First, we have our initial clinical data for BLU-222, our selective CDK2 inhibitor focused on advancing treatment of breast cancer and other CDK2 vulnerable cancers. The data at ASCO will demonstrate evidence of monotherapy safety and pathway modulation. The safety profile is particularly important here as we anticipate that the maximum benefit of BLU-222 will be in combination with other agents such as CDK4/6 inhibitors like ribociclib.

首先，我們擁有 BLU-222 的初步臨床數據，BLU-222 是我們的選擇性 CDK2 抑製劑，專注於推進乳腺癌和其他 CDK2 易受影響癌症的治療。 ASCO 的數據將證明單一療法的安全性和通路調節的證據。安全性在此尤為重要，因為我們預計 BLU-222 的最大益處將與其他藥物（例如 ribociclib 等 CDK4/6 抑製劑）聯合使用。

Following ASCO, we will continue enrollment in monotherapy cohorts and in parallel, continued dose escalation of the combination of ribociclib in breast cancer patients. Second, we have our initial clinical data disclosure for BLU-451 in EGFR exon 20 mutant non-small cell lung cancer.

在 ASCO 之後，我們將繼續納入單一療法隊列，同時繼續增加乳腺癌患者中 ribociclib 組合的劑量。其次，我們披露了 BLU-451 在 EGFR 外顯子 20 突變非小細胞肺癌中的初步臨床數據。

These data will show safety and early clinical activity, including evidence of CNS activity that reinforce best-in-class potential for BLU-451. We're continuing to work through dose escalation cohorts to optimize a dose and regimen and at ASCO we'll show progress to date.

這些數據將顯示安全性和早期臨床活性，包括強化 BLU-451 同類最佳潛力的中樞神經系統活性證據。我們正在繼續通過劑量遞增隊列來優化劑量和治療方案，在 ASCO 上我們將展示迄今為止的進展。

Third, we will present updated dose escalation data on BLU-945, both as monotherapy and in combination with osimertinib in a heavily pretreated EGFR mutant patient population. A key focus of this presentation will be the safety and tolerability of BLU-945 in combination with osimertinib.

第三，我們將提供 BLU-945 的最新劑量遞增數據，無論是作為單藥治療還是與奧西替尼聯合治療，在接受過多次治療的 EGFR 突變患者群體中進行。本次演講的重點是 BLU-945 與奧希替尼聯合使用的安全性和耐受性。

This tolerability is remarkable given the failure of previous EGFR targeted combinations with other EGFR inhibitors and osimertinib due to additive wild-type EGFR toxicity. We are on track for our other important pipeline milestones as well, including nomination of a development candidate targeting wild-type kit for chronic urticaria in the middle of this year.

考慮到先前的 EGFR 靶向組合與其他 EGFR 抑製劑和奧希替尼由於野生型 EGFR 的附加毒性而失敗，這種耐受性是顯著的。我們也有望實現其他重要的管道里程碑，包括在今年年中提名針對慢性蕁麻疹野生型試劑盒的開發候選藥物。

We look forward to sharing more data next month as we reach these milestones and make progress towards our 2027 Blueprint.

隨著我們達到這些里程碑並在 2027 年藍圖方面取得進展，我們期待在下個月分享更多數據。

With that, I'll turn the call over to Mike to review our financial updates.

這樣，我會將電話轉給邁克，以查看我們的財務最新情況。

Thanks, Becker. Earlier this morning, we reported detailed financial results in our press release. And for the call, I'll touch on a few highlights from the quarter.

謝謝，貝克爾。今天早上早些時候，我們在新聞稿中報告了詳細的財務業績。在電話會議中，我將談談本季度的一些亮點。

In the first quarter, total revenues were $63.3 million, including $39.1 million in net product revenues from sales of AYVAKIT and $24.2 million in collaboration and license revenues. As Philina noted, we saw continued growth in AYVAKIT demand that helped drive quarter-on-quarter revenue growth as well as onetime free goods favorability that we expect to unwind in Q2.

第一季度總收入為 6330 萬美元，其中包括 AYVAKIT 銷售帶來的 3910 萬美元產品淨收入以及 2420 萬美元合作和許可收入。正如 Philina 指出的那樣，我們看到 AYVAKIT 需求持續增長，這有助於推動季度收入增長，以及我們預計在第二季度將取消的一次性免費商品優惠。

We are pleased with our progress earlier this year and are now updating our AYVAKIT net product revenue guidance for 2023 to reflect the patient mix favorability that we observed in the first quarter.

我們對今年早些時候的進展感到滿意，現在正在更新 2023 年 AYVAKIT 淨產品收入指引，以反映我們在第一季度觀察到的患者組合偏好。

We now anticipate approximately $135 million to $145 million for our currently approved indications of advanced SM and GIST. Based on our PDUFA date, Q1 is our last full quarter of revenue prior to our anticipated ISM launch.

目前，我們預計用於目前批准的晚期 SM 和 GIST 適應症的費用約為 1.35 億至 1.45 億美元。根據我們的 PDUFA 日期，第一季度是我們預期 ISM 推出之前的最後一個完整季度的收入。

As we have noted, we do not plan to issue guidance, including ISM this year as it will be too early in the launch to do so. We expect to see continued growth in advanced SM through this year, driven by patient demand. Our anticipated label expansion into ISM will be the main driver of AYVAKIT growth in the second half of the year.

正如我們所指出的，我們今年不打算發布包括 ISM 在內的指導意見，因為現在發布還為時過早。我們預計，在患者需求的推動下，先進 SM 的業務今年將持續增長。我們預計標籤向 ISM 的擴張將成為下半年 AYVAKIT 增長的主要推動力。

Turning now to expenses. Our total costs and operating expenses were $187.5 million for the first quarter. Financial discipline remains a priority for Blueprint, and we saw that play out as we showed quarter-over-quarter operating expenses declined for the third consecutive quarter. Similar to our expense guidance from last quarter, we expect a slight increase in operating expenses in the first half of the year related to launch preparations and clinical pipeline investments and then expect a quarter-on-quarter OpEx to be relatively flat for the remainder of the year.

現在轉向費用。第一季度我們的總成本和運營費用為 1.875 億美元。財務紀律仍然是 Blueprint 的首要任務，我們看到了這一點，因為我們顯示季度運營費用連續第三個季度下降。與我們上季度的費用指引類似，我們預計上半年與上市準備和臨床管道投資相關的運營費用將略有增加，然後預計剩餘時間的季度運營支出將相對持平那一年。

In February, we announced that we are in the process of regaining development and commercialization rights for GAVRETO from Roche. We do not anticipate any incremental OpEx impact related in 2023 related to this transition. We have initiated a process to repartner GAVRETO as we believe that this is the best model to drive value going forward as we prioritize our focus on SM. We are in a unique position in that AYVAKIT is a breakthrough medicine that has been significantly derisked and Blueprint Medicines has a clean growth story as we continue to generate commercial revenue and make progress on multiple assets across our clinical pipeline.

今年二月，我們宣布正在從羅氏手中重新獲得 GAVRETO 的開發和商業化權利。我們預計 2023 年不會因這一轉變而產生任何增量運營支出影響。我們已經啟動了與 GAVRETO 重新合作的流程，因為我們相信這是推動價值發展的最佳模式，因為我們優先關注 SM。我們處於獨特的地位，因為 AYVAKIT 是一種突破性藥物，已顯著降低了風險，而 Blueprint Medicines 則擁有乾淨的增長故事，因為我們繼續創造商業收入並在整個臨床管道的多個資產上取得進展。

We remain in an exceptionally strong financial position with nearly $1 billion in cash and a planned reduction in our annual operating cash burn, a trend that we expect will continue as we grow revenues and remain disciplined around operating expenses. This continued financial strength will help fuel our 2027 Blueprint to achieve precision at scale and create transformative value for patients and shareholders.

我們仍然保持著異常強勁的財務狀況，擁有近 10 億美元的現金，併計劃減少年度運營現金消耗，隨著我們收入的增長和運營支出的嚴格控制，我們預計這一趨勢將持續下去。這種持續的財務實力將有助於推動我們的 2027 年藍圖，以實現大規模的精確性，並為患者和股東創造變革性的價值。

With that, I'll now turn the call over to the operator for questions. Operator?

現在，我將把電話轉給接線員詢問問題。操作員？

(Operator Instructions) Your first question comes from Eun Kyung of Jefferies.

（操作員說明）您的第一個問題來自 Jefferies 的 Eun Kyung。

Could you talk about what -- really what types of patients in advanced SM population actually drove increased uptake. And based on why you saw quarter-over-quarter, do you think the third quarter last year is kind of a normal kind of seasonality that you might expect?

您能否談談晚期 SM 人群中哪些類型的患者實際上推動了攝取量的增加。基於您看到季度環比的原因，您認為去年第三季度是您可能期望的正常季節性嗎？

So thank you, Eun. So I think what you're asking is we lost the first part of your question, but I believe what you're asking is, what was the mix kind of the base growth in terms of advanced SM patients. And then just the dynamic quarter-over-quarter. And I think what we've mentioned before is the advanced systems rare disease, and we're going to see lumpiness quarter-over-quarter. It's really kind of what we see over the course of the year that's going to be important there. And we're to see the dynamics that happened here in Q1 and to be able to raise our guidance to $135 million to $145 million. Philina, do you want to talk about the mix in the SM growth?

所以謝謝你，恩。所以我認為你要問的是我們丟失了你問題的第一部分，但我相信你要問的是，晚期 SM 患者的基礎增長的混合類型是什麼。然後就是季度環比的動態。我認為我們之前提到的是先進系統罕見疾病，我們將看到季度環比的情況。這確實是我們在這一年中看到的非常重要的事情。我們將看到第一季度發生的動態，並能夠將我們的指導提高到 1.35 億美元至 1.45 億美元。 Philina，你想談談SM成長中的組合嗎？

Thanks, Eun. So starting with the mix, we were really pleased to see growth across many subtypes of advanced SM especially in the subset of patients who have SM-AHN, which is the most common subtype where we saw a 15% growth in the market share of AYVAKIT into patients with SM-AHN.

謝謝，恩。因此，從混合開始，我們非常高興看到晚期 SM 的許多亞型的增長，尤其是 SM-AHN 患者的子集，這是最常見的亞型，我們看到 AYVAKIT 的市場份額增長了 15% SM-AHN 患者。

To your question about quarter-over-quarter growth, again, I'd say we were extremely encouraged to see 30% growth in Q1 coming out of Q4. As we've talked about growth in advanced SM is something that we continue to see, albeit at a more measured pace than in the early stages of launch. But our greatest growth driver ahead is our pending ISM launch with approval, which we expect to be the most significant source of AYVAKIT growth going forward.

對於你關於季度環比增長的問題，我想說，看到第一季度比第四季度增長 30%，我們感到非常鼓舞。正如我們所討論的，我們將繼續看到先進 SM 的增長，儘管增長速度比發布的早期階段更加謹慎。但我們未來最大的增長動力是我們即將推出並獲得批准的 ISM，我們預計這將成為 AYVAKIT 未來增長的最重要來源。

Follow-up to ISM. So in the past, you mentioned that you were expecting a broad label from the FDA. I don't know if you want to make a comment that we are so close to the FDA action date. But is that still what you are expecting broader label for ISM?

ISM 的後續行動。所以在過去，您提到您期待 FDA 的廣泛標籤。我不知道您是否想發表評論，我們已經接近 FDA 的行動日期了。但這仍然是您所期望的 ISM 更廣泛的標籤嗎？

So Eun, this is Kate. So I don't think we've talked really about what we expect from a label perspective on ISM. And as you said, this close the action date. We don't really talk about the kind of the discussions we're having with the regulatory agencies. Things are on track. We're having a good collaborative discussion, and we're on track for our PDUFA.

所以恩，這是凱特。因此，我認為我們還沒有真正討論過從標籤角度對 ISM 的期望。正如你所說，行動日期就此結束。我們並沒有真正談論我們與監管機構進行的討論。事情正在步入正軌。我們正在進行良好的協作討論，並且我們的 PDUFA 已步入正軌。

(Operator Instructions) our next question comes from Salveen Richter of Goldman Sachs.

（操作員指令）我們的下一個問題來自高盛的 Salveen Richter。

On for Salveen. Just one on the guidance. Are there any other underlying assumptions outside of patient mix that's driving the rate? And then just quickly on the ISM launch. Could you just walk us through how you're planning to target the physicians that have the patients that are adequately controlled with the best supportive care. Do you have a mechanism in place for switching those patients?

薩爾文上場。只是一份指導。除了患者組合之外，是否還有其他潛在的假設推動了這一比率？然後很快就推出了 ISM。您能否向我們介紹一下您計劃如何針對那些通過最佳支持性護理充分控制患者病情的醫生。您是否有適當的機制來轉換這些患者？

So thank you for the question. Just talking about the first part of your question, which is, was there a change in the mix? I mean, really, the 30% growth that we saw was a composition of 2 different dynamics. One is the increase in the base business, which Philina mentioned in her prepared remarks. And the other was a shift in the free goods, the number of patients on free goods, which is a temporary shift. The team did a great job to find a way for the patients who would have traditionally been on free goods in Q1 to get into paid therapy just for the quarter. And so that was a very innovative thing our team was able to do and certainly provided tailwinds in the quarter.

謝謝你的提問。只是談論你問題的第一部分，即組合是否有變化？我的意思是，實際上，我們看到的 30% 的增長是由兩種不同的動力組成的。一是基礎業務的增長，菲莉娜在準備好的發言中提到了這一點。另一個是免費物品的變化，即使用免費物品的患者數量，這是暫時的變化。該團隊做得很好，為那些傳統上在第一季度接受免費商品的患者找到了一種方法，讓他們在本季度接受付費治療。因此，這是我們團隊能夠做的一件非常創新的事情，並且肯定在本季度提供了推動力。

But the growth that we saw was -- it's very much in line with what we've seen before. And there's really no change in patient mix. and in line with how we thought about our previous guidance. Philina, do you want to talk about ISM?

但我們看到的增長與我們之前看到的非常一致。患者組合確實沒有變化。並符合我們對之前指導的看法。 Philina，你想談談 ISM 嗎？

Yes. So I think I heard your second question is really around how are we targeting providers who have patients in need and what are we doing to activate that urgency to treat and sort of move from symptom directed polypharmacy alone to treatment with AYVAKIT.

是的。所以我想我聽說你的第二個問題實際上是關於我們如何針對有需要的患者的提供者，以及我們正在做什麼來激活治療的緊迫性，並從單獨針對症狀的多藥治療轉向 AYVAKIT 治療。

And so really a key focus of our strategy is to target the highest volume AIs and Heme/Oncs. The top 350, as we've talked about, are treating approximately 1,500 already diagnosed moderate to severe ISM patients. Who today are actively engaging with the health care system, seeing their provider on average a couple of times a year.

因此，我們戰略的真正重點是瞄準產量最高的 AI 和血紅素/Onc。正如我們所討論的，前 350 名醫院正在治療大約 1,500 名已診斷為中度至重度 ISM 患者。如今，他們積極參與醫療保健系統，平均每年去看醫生幾次。

In addition to that, we have a substantial armamentarium of tools, right? So every territory is not created equal. And so where there are those high-volume centers, our ABMs are targeting them. They also have extremely powerful data capabilities, as we've talked about in terms of patient journeys that are now equipped for them to be able to see those most severe ISM patients who are engaging with their providers. And on top of that, leveraging their local intel and relationships with customers.

除此之外，我們還有大量的工具，對吧？因此，並非所有領土都是生而平等的。因此，哪裡有那些高流量中心，我們的反導系統就瞄準它們。他們還擁有極其強大的數據能力，正如我們在患者旅程方面所討論的那樣，現在他們能夠看到那些正在與其提供者接觸的最嚴重的 ISM 患者。最重要的是，利用他們的本地情報以及與客戶的關係。

The second part of your question, I think, was around kind of how to drive that switching. I might reframe that actually is sort of activating for the urgency to treat with AYVAKIT. And again, I think that's really a combination of conveying the burden of disease with providers, and there's substantial literature on that front. And secondly, really engaging with patients and caregivers to activate them and let them know when a new treatment option becomes available.

我認為你問題的第二部分是關於如何驅動這種切換。我可能會重新定義，這實際上是一種激活 AYVAKIT 治療的緊迫性。再說一次，我認為這實際上是向提供者傳達疾病負擔的結合，並且在這方面有大量文獻。其次，真正與患者和護理人員接觸，激活他們，並讓他們知道何時有新的治療選擇。

Our next question comes from Ren Benjamin of JMP Securities.

我們的下一個問題來自 JMP 證券的任本傑明。

Can you talk just maybe quantify a little bit of the provider engagement stats that you mentioned. You talked about growing unaided awareness growing to 40%. And is that 40% of the top 350, I mean what's the denominator that we should be thinking about?

您能談談量化一下您提到的提供商參與度統計數據嗎？您談到將獨立意識提高到 40%。我的意思是，我們應該考慮前 350 名中的 40% 的分母是什麼？

And I guess, ultimately, as you get closer to launch, is this something that can go even higher to 60% to 80%? Or do you think this is kind of plateauing here? And just as a follow-up, can you just give us an update as to how payer discussions are progressing.

我想，最終，當你接近發佈時，這個比例是否可以更高到 60% 到 80%？或者你認為現在已經趨於穩定了嗎？作為後續行動，您能否向我們介紹一下付款人討論的最新進展情況。

Thanks for that question, Ren. And we are really pleased with where we sit today and the receptivity of both the data coming out AAAAI. And just as Philina mentioned, about how physicians are aware of innovative medicine that is possibly coming to them. But in, do you want to talk about some of the details on that?

謝謝你提出這個問題，任。我們對今天所處的位置以及對 AAAAI 數據的接受度感到非常滿意。正如菲利娜提到的，關於醫生如何意識到可能到來的創新醫學。但是，您想談談一些細節嗎？

Yes. So I think the first part of your question was around the awareness metric. So again, I think we're just really encouraged to see unaided awareness at 40%, and that's really among the Heme/Oncs and the allergists/immunologists who are actively treating ISM patients today.

是的。所以我認為你問題的第一部分是圍繞意識指標的。再說一遍，我認為我們真的很高興看到 40% 的無輔助意識，而這確實是在當今積極治療 ISM 患者的血紅素/Oncs 和過敏科醫生/免疫學家中。

So including and beyond the top 350 providers we saw a strong bump in this awareness coming out of AAAAI, especially among the allergists/immunologist. And in addition to that, the aided awareness of AYVAKIT is well above 60% at this point. So I would say certainly not plateauing. There's further work to do as we get into sort of lower volume and out towards sort of the tail of treaters and referers.

因此，包括 350 家頂級提供商在內，我們看到 AAAAI 的這種意識大幅提高，特別是在過敏症專家/免疫學家中。除此之外，AYVAKIT 的輔助認知度目前遠高於 60%。所以我想說肯定不會停滯不前。當我們進入較低的數量並朝著治療者和推薦者的尾部發展時，還有更多的工作要做。

The second part of your question, I think, was getting at access and sort of maybe what expectations are in terms of access with payers upon launch. So as we've said, based on our payer insights and sort of the current performance of what we see, we anticipate and we'll be really focused on maintaining strong patient access post approval. All 5 doses of AYVAKIT are on the market, including the 25-milligram and we are certainly seeing strong reimbursement. There's 1 code for SM as well. So for the small proportion of scripts with ISM that we are seeing today, we are seeing those getting good coverage as well.

我認為，你的問題的第二部分是獲得訪問權限，以及在啟動後與付款人的訪問方面的期望是什麼。因此，正如我們所說，根據我們對付款人的見解以及我們所看到的當前表現，我們預計並將真正專注於在批准後保持強大的患者訪問權限。所有 5 劑 AYVAKIT 均已上市，包括 25 毫克劑量，我們當然會看到強勁的報銷。 SM 也有 1 個代碼。因此，對於我們今天看到的一小部分帶有 ISM 的腳本，我們也看到它們得到了很好的覆蓋。

Our next question comes from Brad Canino.

我們的下一個問題來自布拉德·卡尼諾。

I want to ask on the ISM launch really after meeting with physicians since AAAAI, hear are your thoughts around the -- preliminary thoughts, I guess, around how ISM treatment durations may shape up in the real world. I particularly get questions on the 40% of trial patients that received less than a 30% symptom reduction after a year. And if that cohort in the real world may be at risk for shorter durations.

在與 AAAAI 以來的醫生會面後，我想問一下關於 ISM 啟動的問題，我猜想听聽您對 ISM 治療持續時間在現實世界中如何形成的初步想法。我特別收到關於 40% 的試驗患者一年後症狀減輕不到 30% 的問題。如果現實世界中的這個群體可能在較短的時間內面臨風險。

So Brad, thanks for your question. And Becker, can you weigh in on that?

布拉德，謝謝你的提問。貝克爾，你能對此發表意見嗎？

Yes. I think it's -- Brad, it's important to remember that TSS score is not a binary measure patients derive benefit on their most bothersome symptom. Sometimes that includes the total TSS score going down, sometimes it doesn't. But for most of the patients on the study derived benefit -- and what's really important is that patients at all TSS levels have remained on drug for a very long time in the study, including the patients that -- from Part 1 that remain on after many years.

是的。我認為——布拉德，重要的是要記住，TSS 評分不是一個二元衡量標準，患者可以從最煩人的症狀中獲益。有時這會導致 TSS 總分下降，有時則不會。但對於參與該研究的大多數患者而言，真正重要的是，處於所有 TSS 水平的患者在研究中都長期服用藥物，包括從第 1 部分開始，在治療後仍繼續服用藥物的患者。很多年。

So I don't think we're in a position yet to say what the duration is going to be. This is going to be a lifelong treatment, I believe, for many patients. And then we're going to continue to learn of all the ways that AYVAKIT benefits patients beyond what's measured by the TSS score.

因此，我認為我們還不能確定持續時間。我相信，對於許多患者來說，這將是終生的治療方法。然後我們將繼續了解 AYVAKIT 為患者帶來的所有益處，超出了 TSS 評分所衡量的範圍。

And I would just add, Brad, I mean we've said this before, is that when you see the 96% of patients who are on AYVA and Part 2, roll over into Part 3 and continue on therapy in the context of a clinical trial, with having to be part of a protocol. I mean I think that's really a testament and patients really vote with their feet.

我想補充一點，Brad，我的意思是我們之前說過，當你看到 96% 的患者正在接受 AYVA 和第 2 部分時，請轉入第 3 部分並在臨床背景下繼續治療試驗，並且必須成為方案的一部分。我的意思是，我認為這確實是一個證明，患者確實用腳投票。

We've also mentioned that as we've gone out broadly with this data, the response rate criteria that we put in place is really not relevant to the AI community. It's certainly something that hematologist oncologists are familiar with, and we certainly have strong data there that we can discuss with them. But AIs don't really think about that response rate as a metric for which they think about patient benefit.

我們還提到，當我們廣泛使用這些數據時，我們制定的響應率標準實際上與人工智能社區無關。這當然是血液腫瘤學家所熟悉的，我們當然有強有力的數據可以與他們討論。但人工智能並沒有真正將響應率視為他們考慮患者利益的指標。

Our next question comes from Marc Frahm of TD Cowen.

我們的下一個問題來自 TD Cowen 的 Marc Frahm。

This is Ernesto Rodriguez on for Marc. Congratulations on the quarter. We just have a couple on -- a follow-up on the AYVAKIT [bit] and the guidance. So you mentioned some of the growth came from a reduction in the percentage of patients on free drug I was wondering what drove -- what exactly drove that? And why do you think it will be temporary? So how should we think about it going forward?

我是馬克的埃內斯托·羅德里格斯。祝賀本季度。我們剛剛發布了一些內容——關於 AYVAKIT [bit] 的後續行動和指南。所以你提到一些增長來自於免費藥物患者比例的減少，我想知道是什麼推動了這一增長——到底是什麼推動了這一增長？為什麼你認為這將是暫時的？那麼我們應該如何思考未來的發展呢？

And then also wondering if you saw any off-label use of the drug given that we're getting so close to the expect FDA approval in ISM. And then a second question on guidance. Have you guys determined how you plan to address AYVAKIT guidance once the label is expanded?

然後還想知道您是否看到了該藥物的任何超說明書使用，因為我們已經非常接近 FDA 在 ISM 中的預期批准。然後是關於指導的第二個問題。你們是否已決定在標籤擴展後計劃如何處理 AYVAKIT 指南？

Thanks for those questions, and I appreciate that everybody has a lot of questions. We're going to try to keep this given the queue. So maybe I'll answer your last 2 questions quickly. Ernie, and then we can get -- (inaudible) weigh in on how we thought about the growth.

感謝大家提出這些問題，我也很高興大家都有很多問題。我們將盡力在隊列中保持這個狀態。所以也許我會很快回答你的最後兩個問題。厄尼，然後我們可以——（聽不清）權衡我們對增長的看法。

So no, we do not anticipate providing any additional guidance upon the ISM approval. It's going to be early days in a launch, the first therapy ever approved in this disease state, so we will not be issuing guidance. And then we've had very little off-label usage at up. So that remains the same as it was last quarter. We have a few patients, but not many. So maybe Philina, can you weigh in on how we thought about the kind of growth and what happened with the free goods patients.

因此，我們預計不會在 ISM 批准後提供任何額外指導。這是有史以​​來在這種疾病狀態下批准的第一種療法，現在還處於啟動的早期階段，因此我們不會發布指導意見。然後我們很少有超適應症使用。因此，這與上季度相同。我們有一些病人，但不多。那麼菲莉娜，您能否談談我們對這種增長的看法以及免費商品患者發生的情況。

Yes. So what we saw this quarter is that half of the growth that we saw was due to a shift to a greater proportion of patients receiving commercial therapy instead of free goods. And so what happens in Q1 is that patients go through a process where they reverify their benefits and their status.

是的。因此，我們本季度看到的增長有一半是由於越來越多的患者接受商業治療而不是免費商品。因此，第一季度發生的情況是，患者會經歷一個重新驗證其福利和狀態的過程。

We have a very robust patient support program, Your Blueprint, and it's part of their normal process to help in reverifying patient status. In some cases, patients may qualify for additional sources of financial assistance, such as third-party charitable foundations. And if they're able to go on to this, then they are able to move off of free drug and on to commercial therapy. The resources available here are finite. And so for that reason, we expect this to be a temporary onetime benefit that unwinds over the course of second quarter.

我們有一個非常強大的患者支持計劃“您的藍圖”，這是他們幫助重新驗證患者狀態的正常流程的一部分。在某些情況下，患者可能有資格獲得額外的經濟援助來源，例如第三方慈善基金會。如果他們能夠繼續這樣做，那麼他們就能夠擺脫免費藥物並轉向商業治療。這裡可用的資源是有限的。因此，出於這個原因，我們預計這將是一個暫時的一次性好處，將在第二季度結束。

So I just also had one comment that it's important to note that AIs don't typically prescribe off-label. They -- and most of the ones we talked about are anticipating and waiting anxiously for the label, but that's not a general trend like it is with Heme/Oncs.

所以我也有一個評論，重要的是要注意人工智能通常不會開適應症外的處方。他們——以及我們談論的大多數人都在期待和焦急地等待這個標籤，但這並不是像 Heme/Oncs 那樣的總體趨勢。

Our next question comes from Dane Leone of Raymond James.

我們的下一個問題來自 Raymond James 的 Dane Leone。

So just 2 for me. Just clarifying that actually the last point that was made there. I think people are just trying to understand the cadence going into the second quarter where, obviously, you're going to get an approval this month. What we should expect with ASM? So to frame it more broadly, you raised your guidance. Obviously, you feel confident coming out of the first quarter, that things are going well. You're picking up momentum in ASM on the commentary that there's going to be some shift back to patients on free drug.

所以對我來說只有2個。只是澄清一下實際上是那裡提出的最後一點。我認為人們只是想了解進入第二季度的節奏，顯然，你將在本月獲得批准。我們對 ASM 應該有什麼期待？因此，為了更廣泛地構建它，您提出了指導意見。顯然，你對第一季度的表現充滿信心，一切進展順利。有評論稱 ASM 將會重新向患者提供免費藥物，這讓您在 ASM 中獲得了動力。

Can you maybe just help us frame it a little bit. So we were all kind of more dialed into what we should expect maybe the second quarter Q-on-Q to look like for ASM with all those moving pieces. And then could you just frame quickly for us to your expectations for the 945 plus osimertinib first data we'll see at ASCO. Obviously, that seems to be a curtain razor for the L858R patient population that we'll get later in the year. But we would expect to see maybe some initial signs of efficacy between that combination just based on the mechanism of action. So anything there could be helpful as well.

你能幫我們設計一下嗎？因此，我們更加深入地了解了 ASM 第二季度 Q-on-Q 的情況，以及所有這些移動部件。然後，您能否快速向我們描述一下您對我們將在 ASCO 上看到的 945+ 奧希替尼第一個數據的期望。顯然，這似乎是我們將在今年晚些時候獲得的 L858R 患者群體的一把窗簾剃須刀。但我們希望僅根據作用機制就可以看到該組合之間的一些初步功效跡象。所以那裡的任何事情也可能有幫助。

Sure. So Mike, maybe you can take the first point that Dane was making just around how to think about Q2 expectations for the core business and then Becker, we'll hand it over to you for ASCO.

當然。所以邁克，也許你可以採納 Dane 提出的第一點，即如何思考對核心業務的第二季度預期，然後 Becker，我們將把它交給 ASCO 的你。

Yes. So Dane, yes, so as Philina mentioned, we expect to see continued growth in our AYVAKIT business and growth in patient demand but it's not going to be at the same quarter-over-quarter run rate that we saw in Q1 due to this reversal of the free goods impact that we mentioned.

是的。所以 Dane，是的，正如 Philina 提到的，我們預計 AYVAKIT 業務將持續增長，患者需求也將增長，但由於這一逆轉，季度環比運行率不會與第一季度相同。我們提到的免費商品的影響。

And you can think about it almost as -- so we've increased our guidance by $5 million. That's approximately what the impact of the free goods was. And so you can almost think about the base to grow revenue off of for Q2 as being like closer to $34 million. And we still expect to see moderate growth off of that going forward, consistent with what Philina said, and that is consistent with our increase in guidance.

您幾乎可以將其視為 - 所以我們將指導增加了 500 萬美元。這大約就是免費商品的影響。因此，您幾乎可以認為第二季度收入增長的基礎接近 3400 萬美元。我們仍然預計未來會出現溫和增長，這與菲利納所說的一致，也與我們增加的指導一致。

I think the other important point for Q2 is, yes, we are going to be getting anticipated ISM approval. This quarter, we expect the ISM impact to be pretty minimal. Where you're going to see the growth for ISM really come in as the back half of the year.

我認為第二季度的另一個重要點是，是的，我們將獲得預期的 ISM 批准。本季度，我們預計 ISM 的影響非常小。您將在今年下半年看到 ISM 的真正增長。

Becker, do you want to take the 945 question for ASCO?

Becker，您想回答 ASCO 的 945 問題嗎？

Yes. So Dane, thanks for mentioning the 945 plus combination. That is a combination we're very excited about. This is an update on our Phase I part of the study. As you know, patients in Phase I are heavily pretreated and have quite complex tumors. What we're looking at here is really safety and tolerability of this combination. This is really the first time that full doses of 2 EGFR inhibitors with different side effect profiles are being combined. We look to the activity data to validate that the compounds hit the mutations that they're expected to, and we've shared some of that data in the past. And so that's really the expectation with respect to efficacy in a heavily appreciated patient population, but the safety is what we are focusing on at ASCO.

是的。 Dane，感謝您提及 945 plus 組合。這是我們非常興奮的組合。這是我們第一階段研究部分的更新。如您所知，第一階段的患者接受了大量的預處理，並且腫瘤相當複雜。我們在這里關注的是這種組合的真正安全性和耐受性。這確實是第一次將兩種具有不同副作用的 EGFR 抑製劑的全劑量組合起來。我們通過活性數據來驗證這些化合物是否能夠達到預期的突變，並且我們過去已經分享過其中的一些數據。因此，這確實是對深受好評的患者群體的療效的期望，但安全性是 ASCO 關注的重點。

Our next question comes from Michael Schmidt of Guggenheim.

我們的下一個問題來自古根海姆的邁克爾·施密特。

This is Paul on for Michael. I have one on BLU-451 data at ASCO. Just wondering if you could set some expectations how are you thinking about the bar for next-gen exon 20 targeted therapy to sort of shift the treatment practice in the second-line plus setting.

這是保羅替補邁克爾。我在 ASCO 上有一份 BLU-451 數據。只是想知道您是否可以設定一些期望，您如何看待下一代外顯子 20 靶向治療的標準，以改變二線及以上環境中的治療實踐。

And then maybe if I could squeeze a quick one in on GAVRETO. Anything you can share on those potencies that you've initiated to repartner and sort of how your confidence is in finding a new partner in the near term, that would be helpful.

然後也許我可以快速擠進加夫雷托。您可以分享的任何關於您已開始重新尋找合作夥伴的潛力以及您對在短期內尋找新合作夥伴的信心如何，這都會有所幫助。

Yes. So thank you for the question. Becker can take the 451, but maybe I'll just address GAVRETO first. So from a GAVRETO perspective, we are very confident that we will be able to find a great partner for this product, and it is an important medicine that has a tremendous impact on patients with RET-driven cancers, and we've got a lot of interest. And so we're highly confident that we're going to be able to find a great partner for that. And then maybe, Becker, do you want to go to BLU-451?

是的。謝謝你的提問。貝克爾可以乘坐 451，但也許我會先談談加夫雷托。所以從 GAVRETO 的角度來看，我們非常有信心能夠為這個產品找到一個很好的合作夥伴，它是一種重要的藥物，對 RET 驅動的癌症患者有巨大的影響，我們已經有很多出於興趣。因此，我們非常有信心能夠為此找到一個優秀的合作夥伴。然後也許，Becker，你想去 BLU-451 嗎？

Yes. So just to remind everyone, BLU-451 51 is a compound we acquired for its ability to cross the blood-brain barrier, and so you've hit exon 20 without hitting wild-type EGFR. So to spare patients the toxicity of what we've seen with some of the other compounds and then to be able to address the most common area for relapse, which is the central nervous system.

是的。所以提醒大家，BLU-451 51 是我們獲得的一種化合物，因為它能夠穿過血腦屏障，因此您已經擊中了外顯子 20，而沒有擊中野生型 EGFR。因此，為了讓患者免受我們在其他一些化合物中看到的毒性的影響，然後能夠解決最常見的複發區域，即中樞神經系統。

So we're in dose escalation right now, still escalating. So I'm not -- don't expect an ORR from this early study. But what we are anticipating showing is the level of activity that we've seen, we've already shared that we've seen activity at all of the dose levels. So this will be an update on this and central nervous system activity as we continue to escalate the compound.

所以我們現在正處於劑量遞增階段，而且還在不斷增加。所以我不——不要指望這項早期研究能產生 ORR。但我們期望顯示的是我們所看到的活動水平，我們已經分享過我們已經看到了所有劑量水平的活動。因此，隨著我們繼續升級該化合物，這將是有關該藥物和中樞神經系統活動的更新。

Our next question comes from Joel Beatty of (inaudible).

我們的下一個問題來自（聽不清）的喬爾·比蒂。

This is Benjamin Paluch on for Joel. I just had a clarifying question. What's driving the 15% growth in SM-AHN? And then would you expect that to continue?

這是喬爾的本傑明·帕魯克。我只是有一個澄清的問題。是什麼推動 SM-AHN 增長 15%？然後你會期望這種情況繼續下去嗎？

Sure. Philina, do you want to talk about the SM-AHN, and the work we've been doing there?

當然。 Philina，您想談談 SM-AHN 以及我們在那裡所做的工作嗎？

Yes. Thanks for that question. So as you mentioned, we were really encouraged to see 15% growth in the market share into SM-AHN. I think just for context, into the overall advanced SM market. It's still a relatively small proportion of the patients who are being treated for their SM.

是的。謝謝你提出這個問題。正如您提到的，看到 SM-AHN 市場份額增長 15%，我們感到非常鼓舞。我認為只是為了背景，進入整個先進的 SM 市場。在接受 SM 治療的患者中，這一比例仍然相對較小。

And the dynamic there is that most of these patients have SM-AHN and really the education there is focused on the awareness of the SM and the urgency to treat the SM where providers, Heme/Oncs, have traditionally been attuned more to treating the AHN.

動態是，這些患者中的大多數患有 SM-AHN，實際上，那裡的教育重點是對 SM 的認識以及治療 SM 的緊迫性，而提供者、Heme/Oncs 傳統上更傾向於治療 AHN 。

I think to answer your question, primarily, there's still a lot of head space because it is on the order of just a minority of overall patients who are being treated for their SM.

我想回答你的問題，首先，仍然有很大的空間，因為只有少數正在接受 SM 治療的患者。

Our next question comes from Matt Biegler of Oppenheimer.

我們的下一個問題來自奧本海默的馬特·比格勒。

So I guess as we think about modeling AYVAKIT sales going forward, assuming the positive PDUFA, and I appreciate you don't want to give concrete guidance yet, but will you break out ISM sales relative to ASM sales? And do you expect to get a separate J-code for ISM and is that needed to be able to provide concrete guidance?

因此，我想，當我們考慮對未來的 AYVAKIT 銷售進行建模時，假設 PDUFA 為正值，我理解您還不想提供具體指導，但您會列出相對於 ASM 銷售的 ISM 銷售嗎？您是否期望獲得 ISM 的單獨 J 代碼？這是否需要能夠提供具體指導？

So thanks for the question. So what we've talked about before is that the code for SM is actually the same. So we will not be breaking out ISM versus advanced SM. We certainly have a certain level of insight into that dynamic, but we do not have full visibility just based on the channels through which the product flows.

謝謝你的提問。所以我們之前講的是SM的代碼其實是一樣的。因此，我們不會將 ISM 與高級 SM 進行區分。我們當然對這種動態有一定程度的洞察力，但僅僅基於產品流動的渠道，我們並沒有完全的可見性。

We are -- we will be making sure we've talked about some of the KPIs we'll be using around launch and how to help you all think about the impact of the launch, and that's going to include putting out new patient starts, which we started last quarter, and we've updated here looking at the breadth of prescribers and the activation of new accounts. So those are the types of metrics we'd suggest that people look towards as we think about the health of the ISM launch. Philina, do you want to add to that?

我們將確保我們已經討論了我們將在發布過程中使用的一些關鍵績效指標，以及如何幫助大家思考發布的影響，這將包括啟動新的患者，我們從上個季度開始，我們在這裡更新了處方者的廣度和新帳戶的激活情況。因此，當我們考慮 ISM 發布的健康狀況時，我們建議人們關注這些類型的指標。菲莉娜，你想補充一下嗎？

Yes, just to jump in and clarify completely agree with what Kate said. Just to clarify, the one point is it's not the new patient starts, but the total patients on therapy with AYVAKIT that we'll report going forward.

是的，只是想介入並澄清完全同意凱特所說的。需要澄清的是，我們接下來報告的不是新患者開始的情況，而是接受 AYVAKIT 治療的患者總數。

Our next question comes from Ami Fadia of Needham.

我們的下一個問題來自尼達姆的 Ami Fadia。

Can you talk about some of the physicians that you've identified that are already subscribing AYVAKIT? And if you can give us some color on how many ISM patients are under their care. And maybe at least qualitatively, how quickly do you see them prescribing AYVAKIT to their ISM patients?

您能談談您確定的一些已經訂閱 AYVAKIT 的醫生嗎？您能否告訴我們有多少 ISM 患者正在接受他們的護理？也許至少從質量上來說，您看到他們向 ISM 患者開出 AYVAKIT 處方的速度有多快？

Thanks, Ami. So I think what you're kind of asking about is, how do we think about the dynamics early in launch, who will be those early adopters? And are the physicians who have some current experience, we expect that to be one of those groups. But Philina, do you want to weigh in on that?

謝謝，阿米。所以我認為你想問的是，我們如何看待發布初期的動態，誰將是那些早期採用者？目前擁有一些經驗的醫生，我們希望他們成為這些群體之一。但是菲莉娜，你想對此發表意見嗎？

Yes. To the first part of your question, as we've talked about, there's around 460 accounts, so really good breadth of prescribing for AYVAKIT for the current indications, which is a great foundation heading into the ISM launch.

是的。對於你問題的第一部分，正如我們所討論的，大約有 460 個賬戶，因此針對當前適應症的 AYVAKIT 處方範圍確實很廣，這為 ISM 的推出奠定了良好的基礎。

We estimate that the current prescriber base is managing around 400 already diagnosed moderate to severe ISM patients. The second part of your question was really around the speed of the ramp, and we expect that to come both from existing prescribers as well as new prescribers, particularly as we are engaging a number of allergists/immunologist have received, I think, a really excited reception, and they are really waiting for AYVAKIT approval.

我們估計，目前的處方者正在管理約 400 名已確診的中度至重度 ISM 患者。你問題的第二部分實際上是關於坡道的速度，我們希望這既來自現有的處方者，也來自新的處方者，特別是當我們正在與一些過敏症專家/免疫學家合作時，我認為他們已經收到了真正的接待很興奮，他們真的在等待 AYVAKIT 的批准。

And truly the exact cadence of that ramp is going to be hard to predict, right? So these are early quarters in a first-to-market new therapy. And so it's always harder to predict those early quarters until we have a couple under our belt. And again, that's why those KPIs that Kate alluded to are going to be so important in tracking the trajectory of our early launch.

事實上，該斜坡的確切節奏很難預測，對嗎？因此，目前還處於首次上市新療法的早期階段。因此，在我們掌握一些情況之前，預測早期的幾個季度總是比較困難。再說一次，這就是為什麼凱特提到的那些關鍵績效指標對於跟踪我們早期發布的軌跡如此重要。

And maybe a quick follow-up there. So out of these 460 accounts are almost then mostly sort of oncologist because they presumably prescribing AYVAKIT to ASM patients. Are they predominantly...

也許會有一個快速的後續行動。因此，這 460 個賬戶中幾乎大部分都是腫瘤科醫生，因為他們大概給 ASM 患者開了 AYVAKIT 處方。他們主要是...

So the answer to your question is yes, because the current indications are primarily managed by oncology.

所以你的問題的答案是肯定的，因為目前的適應症主要是由腫瘤學來管理的。

Our next question comes from Andrew Berens of SVB Securities.

我們的下一個問題來自 SVB 證券的安德魯·貝倫斯 (Andrew Berens)。

Two questions for me. Maybe the first one is for Mike. I know you said that integrated in the GAVRETO program wouldn't impact expenses in 2023 and you're trying to repartner it, what is the potential impact in 2024 if you have to integrate the program and manage the ongoing trials without a partner.

有兩個問題問我。也許第一個是給邁克的。我知道您說過，整合到 GAVRETO 計劃中不會影響 2023 年的費用，並且您正在嘗試重新合作，如果您必須整合該計劃並在沒有合作夥伴的情況下管理正在進行的試驗，那麼 2024 年的潛在影響是什麼。

Does your cash runway assume divestiture of GAVRETO and then maybe a question on the CDK2 program. What did you have to add to the trial protocol to have the clinical hold renewed?

您的現金跑道是否假設剝離 GAVRETO，然後可能是關於 CDK2 計劃的問題。您必須在試驗方案中添加哪些內容才能更新臨床保留？

Maybe starting to GAVRETO, Mike, do you want to weigh in on how we're thinking about any additional expenditure and just our discipline around our view on that. And then Becker, you can go to 222.

也許從加夫雷托開始，邁克，你想談談我們如何考慮任何額外支出以及我們對此的看法。然後貝克爾，你可以去222。

Yes. I think -- yes, so Andy, like as we mentioned, we're in the process to repartner GAVRETO. We feel very confident about how that is going. And that leads to our belief that we will not see any operating expense -- incremental operating expense impact this year or in future years beyond what we've planned. If anything, we could possibly see a benefit going forward.

是的。我想 - 是的，所以安迪，就像我們提到的那樣，我們正在與加夫雷托重新合作。我們對事情的進展非常有信心。這使我們相信，我們不會看到任何運營費用——今年或未來幾年增量運營費用的影響不會超出我們的計劃。如果有的話，我們可能會看到未來的好處。

So we feel very confident about that position. We don't anticipate any impact on how we guide to our long-term sustainability.

所以我們對這個職位非常有信心。我們預計不會對我們指導長期可持續發展的方式產生任何影響。

And I'll just add to that, Andy. This is an area that we have a lot of control over as we think about our operating expenses and what we choose to allocate our capital to and spend on. I know a lot of you have in your models that we're going to be raising in significant amounts of money going forward. And again, that is not our assumption nor do we intend in any way shape or form to do that. Becker, do you want to talk about BLU-222?

安迪，我要補充一點。當我們考慮我們的運營支出以及我們選擇的資本分配和支出時，我們可以在這個領域擁有很大的控制權。我知道你們中的很多人都有自己的模型，我們將在未來籌集大量資金。再說一次，這不是我們的假設，我們也不打算以任何方式或形式這樣做。 Becker，你想談談 BLU-222 嗎？

Yes. Andy, part of the reason the hold was lifted so quickly is because the changes were minimal and the concern was allayed when we went through the data. So we added baseline ophthalmologic exams for patients. And then if patients had symptoms, they'll get a follow-up. But that was -- that and the FDA toxicity criteria were the only real addition to the protocol.

是的。安迪，如此快地解除保留的部分原因是變化很小，並且當我們查看數據時，擔憂得到了緩解。因此我們為患者增加了基線眼科檢查。如果患者出現症狀，他們將得到隨訪。但那就是——FDA 毒性標準是該方案唯一真正的補充。

And you don't anticipate that will change anything around the cadence of enrollment or anything like that?

您預計這不會改變招生節奏或類似的事情嗎？

No, there's no change expected for patients.

不，預計患者不會發生任何變化。

Our next question comes from David Lebowitz of Citi.

我們的下一個問題來自花旗銀行的大衛·勒博維茨。

Regarding the change in guidance for AYVAKIT, can we assume that the incremental increase is primarily from the onetime charge in the quarter or that's the one time charge for one time benefit.

關於 AYVAKIT 指引的變化，我們是否可以假設增量增長主要來自本季度的一次性費用，或者是一次性福利的一次性費用。

Onetime benefit, that's exactly. Everything else we expect to be the same.

一次性的好處，就是這樣。我們期望的其他一切都是一樣的。

Got it. And on the ISM launch, when you look forward, I understand you're not going to or not able to give any guidance or anything like that. But when you look forward to the launch, what dynamics should we be attuned for given the differences between the ASM and ISM population in terms of potential cadence how long it takes to get the patient from prescription to being on therapy and other such items.

知道了。關於 ISM 的發布，當您展望未來時，我知道您不會或無法提供任何指導或類似的內容。但是，當您期待該產品的推出時，考慮到 ASM 和 ISM 人群在潛在節奏、患者從處方到接受治療所需的時間以及其他此類項目方面的差異，我們應該調整哪些動態。

So Philina has mentioned or talked a little bit on the call today already about how to think about that ramp cadence and the KPIs. Philina, do you want to reiterate that?

Philina 在今天的電話會議上已經提到或談到瞭如何考慮斜坡節奏和 KPI。菲莉娜，你想重申一下嗎？

Yes. I mean I would start with, I think the biggest difference is really the number of prevalent patients who have already been diagnosed and are really actively seeking treatment and are on symptom directed polypharmacy right. So starting off with -- they're about 15 fold greater starting patient population for ISM.

是的。我的意思是，我首先認為，最大的區別實際上是已經被診斷出來、正在積極尋求治療並且正在接受針對症狀的多藥治療的患病患者的數量。因此，首先，ISM 的起始患者人數大約是原來的 15 倍。

To your question around cadence. The area we're really, I think, most highly focused around is driving that urgency to treat, right? While these patients have significant need and are taking polypharmacy and are still facing limitations on their activities of daily living, their ability to work or participate in family activities.

關於你關於節奏的問題。我認為，我們真正最關注的領域是推動治療的緊迫性，對嗎？雖然這些患者有很大的需求並且正在服用多種藥物，但他們的日常生活活動、工作或參與家庭活動的能力仍然面臨限制。

It still is a behavior switch for these patients to move from symptom directed therapy to being treated with a disease-modifying agent. And so that really is one of the core focus areas of our work engaging both providers and educating them on disease burden and activating the patients. We've talked about the cadence of these patient visits are on average about 2x a year.

對於這些患者來說，從症狀導向治療轉向接受疾病緩解藥物治療仍然是一種行為轉變。因此，這確實是我們工作的核心重點領域之一，讓醫療服務提供者參與進來，對他們進行有關疾病負擔的教育，並激活患者。我們已經討論過這些患者就診的頻率平均每年大約 2 次。

And so this education is really important to maximize the urgency to treat and the decision to treat with AYVAKIT at these visits.

因此，這種教育對於最大限度地提高治療的緊迫性和在這些就診時使用 AYVAKIT 治療的決定非常重要。

Our next question come from Peter Lawson of Barclays.

我們的下一個問題來自巴克萊銀行的彼得勞森。

It is (inaudible) on for Peter. So it sounds like there was 2 key dynamics here for the bump in product revenue, both with the free drug dynamics and also some growth in ASM. Could you add a little more color on how much was really driven by organic growth in the ASM market? And maybe what we could be thinking about for growth trajectory there for ASM for the rest of the year?

彼得（聽不清）已經開始了。因此，聽起來產品收入的增長有兩個關鍵動力，既包括免費藥物的動力，也包括 ASM 的一些增長。您能否進一步說明一下 ASM 市場的有機增長到底有多大推動力？也許我們可以考慮一下今年剩餘時間內 ASM 的增長軌跡？

Yes, sure. So what we said is we had a 30% quarter-over-quarter growth. About half was due to the base business growth that's in the advanced SM and about half was due to the favorability around the free goods mix. Thanks for the question.

是的，當然。所以我們所說的是我們的季度環比增長了 30%。大約一半是由於高級 SM 中的基礎業務增長，大約一半是由於對免費商品組合的青睞。謝謝你的提問。

Our next question comes from Zhiqiang Shu of Berenberg.

我們的下一個問題來自貝倫貝格的舒志強。

First one, I want to ask the earlier comment you made around 25 mg dose strength is already in the channel. I wonder if you can talk about the significance of that, both in terms of the launch readiness as well as the importance of that metric for you internally and for analysts to track the use of describing in the ISM patient population.

首先，我想問一下您之前發表的關於 25 毫克劑量強度的評論已經在頻道中了。我想知道您是否可以談談這一點的重要性，無論是在發布準備情況方面，還是該指標對於您內部以及分析師跟踪 ISM 患者群體中描述使用情況的重要性。

And then the second question is around the CDK2 BLU-222 program. Maybe can you talk about the safety matrix that we're going to see at the vascular and also around the pathway modulation signal you were referring to.

第二個問題是圍繞CDK2 BLU-222程序的。也許您可以談談我們將在血管以及您提到的通路調製信號周圍看到的安全矩陣。

Thank you for those questions. Starting with the 25 mg question, I mean I think one thing that's really unique about this launch and this opportunity is the fact that AYVAKIT is available in all dosage strengths are already in the channel. They're being covered by payers. And that really gives us kind of a very fast out of the gate opportunity. And Philina, I don't know if we'll add any more color to that.

謝謝你提出這些問題。從 25 毫克的問題開始，我的意思是，我認為這次發布和這次機會的真正獨特之處在於，AYVAKIT 的所有劑量規格均已在渠道中提供。他們被付款人覆蓋。這確實給了我們一個非常快速的機會。菲利娜，我不知道我們是否會為此添加更多色彩。

Yes. I mean I think we've to the access part already. I think that the difference between this and a de novo launch is for a first-time launch or a dosage strength that wasn't yet kind of on the market. There would be additional lag time needed, right, upon the label coming in and getting that product into the channel. And that doesn't exist for the situation that we are in.

是的。我的意思是我認為我們已經進入了訪問部分。我認為這與從頭推出之間的區別在於首次推出或市場上尚未出現的劑量強度。在標籤進入並將該產品進入渠道時，將需要額外的延遲時間，對吧。對於我們所處的情況來說，這是不存在的。

So that's a great strength that we have coming into this launch. So -- and then Becker, do you want to talk a little bit about BLU-222 and what do you expect from a safety, like what are you looking for from a safety perspective?

因此，這是我們此次發布的強大優勢。那麼，Becker，你想談談 BLU-222 以及你對安全性的期望嗎？比如從安全角度來看你在尋找什麼？

Yes. So just a reminder, BLU-222 was designed and selected to be highly selective such that it hits CDK2 but does not hit CDK1.

是的。所以提醒一下，BLU-222 的設計和選擇具有高度選擇性，因此它可以擊中 CDK2，但不會擊中 CDK1。

And when you hit CDK1, you can get hematologic and gastrointestinal toxicity. So really showing that we're in an active range without seeing that type of side effects is going to be important, both as a single agent and when we think about combination with ribociclib.

當您擊中 CDK1 時，您可能會出現血液學和胃腸道毒性。因此，無論是作為單一藥物還是當我們考慮與 ribociclib 聯合使用時，真正表明我們處於活性範圍內而沒有看到此類副作用將是很重要的。

And then your second question was about what to expect in the biomarker front. What I'll say is that we have both circulating and tumor-based biomarkers, and we look to show at various doses, modulation of that to ensure people that this is a bona fide CDK2 inhibitor that has a pretty wide active range.

然後你的第二個問題是關於生物標記物方面的預期。我要說的是，我們擁有循環生物標誌物和基於腫瘤的生物標誌物，並且我們希望以不同劑量展示其調節，以確保人們這是一種真正的 CDK2 抑製劑，具有相當廣泛的活性範圍。

There are no further questions at this point. Ms. Haviland, I will turn the call over back to you.

目前沒有其他問題。哈維蘭女士，我會將電話轉回給您。

Thanks, operator, and thank you all for taking the time to join us today and for your continued support of Blueprint Medicines. It is going to be an exciting month for us, and we really look forward to talking to all of you again soon.

感謝操作員，感謝大家今天抽出時間加入我們，並感謝你們對 Blueprint Medicines 的持續支持。這對我們來說將是令人興奮的一個月，我們真誠地期待很快再次與大家交談。

And given that it's May 4th, I'd be remiss to not end the call by saying, "May the 4th Be With You" for all the Star Wars fans out there. So again, look forward to talking to you all hopefully in a couple of weeks.

鑑於今天是 5 月 4 日，我在電話結束時沒有對所有星球大戰迷說“願 4 日與你同在”，那就太失職了。所以，再次期待在幾週內與大家交談。

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

謝謝。今天的電話會議到此結束。您現在可以斷開連接。