Blueprint Medicines Corp (BPMC) 2024 Q2 法說會逐字稿

Hello, everyone. At this time, I would like to welcome everyone to the Blueprint Medicines second quarter 2024 financial results conference call. My name is Bruno and I'll be operating your call today. (Operator Instructions)

大家好。現在，我歡迎大家參加 Blueprint Medicines 2024 年第二季財務業績電話會議。我的名字是布魯諾，今天我將接聽您的電話。（操作員說明）

I'll now hand over to your host Jenna Cohen. Please you may begin your conference.

現在我將請主持人珍娜·科恩 (Jenna Cohen) 發言。請開始您的會議。

Thank you, Bruno. Good morning, everyone, and welcome to Blueprint Medicines' second quarter 2024 financial and operating results conference call. 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 Investor's section of our website at www.blueprintmedicines.com.

謝謝你，布魯諾。大家早安，歡迎參加 Blueprint Medicines 2024 年第二季財務與營運業績電話會議。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。您可以造訪我們網站 www.blueprintmedicines.com 的投資者部分，造訪新聞稿以及我們將審查的幻燈片。

Joining me today are Kate Haviland, Chief Executive Officer; Philina Lee, Chief Commercial Officer; Christin Rossi, Chief Operating Officer; and Michael Landsittel, Chief Financial Officer. Fouad Namouni, President, Research and Development is also on the line and available during Q&A.

今天加入我的是執行長凱特哈維蘭 (Kate Haviland)； Philina Lee，首席商務長；克莉絲汀‧羅西，營運長；和財務長 Michael Landsittel。研發部總裁 Fouad Namouni 也在線上並在問答環節中提供協助。

Before we begin, I'd like to remind you that some of the statements made during the call today are forward-looking statements as outlined on slide 3 and are subject to a number of risks and uncertainties. These may cause our actual results to differ materially including those described in our reports filed with the SEC. You are cautioned not to place any undue reliance on these forward-looking statements and Blueprint disclaims any obligation to update such statements.

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是幻燈片 3 中概述的前瞻性陳述，並受到許多風險和不確定性的影響。這些可能導致我們的實際結果有重大差異，包括我們向 SEC 提交的報告中所述的結果。請您注意不要過度依賴這些前瞻性陳述，Blueprint 不承擔任何更新此類陳述的義務。

I'll now hand the call over to Kate.

我現在將電話轉給凱特。

Thank you, Jenna and good morning, everyone. This quarter marks a milestone one full year since the US approval of AYVAKIT for indolent systemic mastocytosis. At the beginning of the year, we laid out that our top priority of the company is AYVAKIT launch execution.

謝謝你，珍娜，大家早安。本季標誌著自美國批准 AYVAKIT 治療惰性系統性肥大細胞增多症以來整整一年的里程碑。今年年初，我們提出公司的首要任務是 AYVAKIT 的推出執行。

And we have delivered yet another very strong quarter of revenue, one that exceeded our own expectations as we continue to build this new rare disease market. This is one of the most exciting rare disease launches happening today, as each quarter makes AYVAKIT path to a greater than $2 billion peak revenue opportunity not much clear.

隨著我們繼續打造這個新的罕見疾病市場，我們又實現了非常強勁的季度收入，超出了我們自己的預期。這是當今最令人興奮的罕見疾病發布之一，因為每個季度 AYVAKIT 通往超過 20 億美元峰值收入機會的道路都不太明確。

Our conviction in AYVAKIT multibillion-dollar market opportunity is based on the positive reception and adoption of AYVAKIT, we are seeing across physicians, patients and payers, as we successfully change the treatment paradigm for patients with SM.

我們對 AYVAKIT 數十億美元市場機會的信念是基於 AYVAKIT 的積極接受和採用，我們在醫生、患者和付款人中看到，隨著我們成功改變 SM 患者的治療模式。

AYVAKIT offers a unique and multidimensional value proposition, a medicine that targets the source of SM, driving deep and durable benefits, while importantly, also being very well tolerated, enabling patients to stay on AYVAKIT over the long term.

AYVAKIT 提供了獨特的多維價值主張，這種藥物針對 SM 的來源，帶來深遠而持久的益處，同時重要的是，它的耐受性也非常好，使患者能夠長期留在 AYVAKIT 上。

As we increase the number of ISM patients on therapy, the cumulative effects of patients staying on therapy will be a significant driver of revenue this year and beyond. Today, we're raising revenue guidance based on our strong performance in the first half of this year.

隨著我們增加接受治療的 ISM 患者數量，繼續接受治療的患者的累積效應將成為今年及以後收入的重要推動力。今天，我們根據今年上半年的強勁表現上調了收入指引。

With a full year of launch now under our belts and our growing experience with the range of factors that drive our business, we have more confidence in this guidance and how we will end the year. Philina will discuss these factors driving commercial performance in more detail in a few minutes.

隨著我們推出一整年的產品，以及我們對推動我們業務的一系列因素的經驗不斷增長，我們對這項指導以及我們將如何結束這一年更有信心。Philina 將在幾分鐘內更詳細地討論這些推動商業績效的因素。

We have just started scratching the surface on reaching the patients with SM, who could potentially benefit from treatment with AYVAKIT. And we expect the AYVAKIT will drive continued and sustainable revenue growth over the long term, enabling us to invest in our prioritized areas of research and development, focus in mast cell driven disorders, where there is high medical need in large patient populations and where we can leverage our expertise and infrastructure to drive the next phase of value inflection of Blueprint Medicine.

我們剛開始觸及 SM 患者的表面，他們可能會從 AYVAKIT 的治療中受益。我們預計AYVAKIT 將在長期內推動持續、可持續的收入成長，使我們能夠投資於我們的優先研發領域，重點關注肥大細胞驅動的疾病，在這些領域，大量患者群體有很高的醫療需求，並且我們可以利用我們的專業知識和基礎設施來推動 Blueprint Medicine 下一階段的價值轉變。

We are pleased to have received I&D clearance for BLU-808, our wild-type KIT inhibitor and we have initiated the healthy volunteer study. We believe BLU-808 has the potential to impact core biology across a number of muscle diseases by targeting KIT. Christy will review our progress today across our entire portfolio later on the call.

我們很高興獲得 BLU-808（我們的野生型 KIT 抑制劑）的 I&D 許可，並且我們已經啟動了健康志願者研究。我們相信 BLU-808 有潛力透過靶向 KIT 來影響多種肌肉疾病的核心生物學。克里斯蒂將在稍後的電話會議上回顧我們今天整個投資組合的進展。

With the foundation of significant and growing revenue from AYVAKIT, a next wave of therapies in our pipeline that address important medical needs and even larger scale patient opportunities and a financial profile anchored by sustainable top line revenue growth, we have the financial flexibility to invest in innovation and we have compelling opportunities in our portfolio that will drive the next wave of value creation as we continue building Blueprint Medicines. Mike will add more color to our financials to close us out.

憑藉AYVAKIT 的可觀且不斷增長的收入基礎，AYVAKIT 是我們管道中的下一波療法，可滿足重要的醫療需求，甚至更大規模的患者機會，以及以可持續的收入增長為基礎的財務狀況，我們擁有財務靈活性來投資創新，我們的產品組合中擁有令人信服的機會，隨著我們繼續打造 Blueprint Medicines，這些機會將推動下一波價值創造。麥克將為我們的財務狀況增添更多色彩，以使我們結束。

With that, I'll turn it over to Philina for more detail on our commercial performance.

接下來，我會將其交給 Philina，以了解有關我們商業表演的更多詳細資訊。

Thanks, Kate. In the second quarter, AYVAKIT achieved $114.1 million in net product revenue, including $101.5 million in the US and $12.7 million, ex-US. AYVAKIT revenue has grown by more than 185% year-over-year, reflecting our strong execution as we capture this unique rare disease opportunity.

謝謝，凱特。第二季度，AYVAKIT 實現產品淨收入 1.141 億美元，其中美國市場收入 1.015 億美元，美國以外市場收入 1,270 萬美元。AYVAKIT 營收年增超過 185%，反映出我們在抓住這一獨特的罕見疾病機會時的強大執行力。

Second quarter growth in the US was driven by continued positive trends across key business fundamentals, growth in patients on AYVAKIT driven by new patient starts and low discontinuation rates, high compliance and continued upside in our commercial versus free goods mix. And our international team had an exceptional quarter.

美國第二季度的成長得益於關鍵業務基本面的持續積極趨勢、新患者入院率推動的 AYVAKIT 患者數量增長、低停藥率、高合規性以及我們的商業商品與免費商品組合的持續上升。我們的國際團隊度過了一個出色的季度。

Let's take a closer look at what drove our business this quarter and what we expect to see for the rest of the year. First, we continue to see strong and steady growth in patients on AYVAKIT driven by new patient starts and low discontinuation rates.

讓我們仔細看看本季業務的推動因素以及我們對今年剩餘時間的預期。首先，在新患者入院率和低停藥率的推動下，我們持續看到 AYVAKIT 患者數量強勁且穩定的成長。

We've seen a consistent pace of new patient starts over the first half of the year. These new patient starts are coming from an expanding AYVAKIT prescriber base that continues to grow in breadth and depth.

我們看到今年上半年新病患的入院速度始終如一。這些新患者來自不斷擴大的 AYVAKIT 處方者基礎，該基礎的廣度和深度持續增長。

We continue to see low discontinuation rates consistent with a multiyear duration of therapy in ISM. Once patients start AYVAKIT, they're staying on treatment. This will continue to drive our base of patients on therapy and be an increasingly important growth driver over time. Patient compliance also remains strong, further reflecting how the compelling clinical profile in PIONEER is playing out in the real world.

我們繼續看到較低的停藥率與 ISM 的多年治療持續時間一致。一旦患者開始使用 AYVAKIT，他們就會繼續接受治療。這將繼續推動我們的患者接受治療，並隨著時間的推移成為越來越重要的成長動力。患者的依從性也仍然很高，這進一步反映了 PIONEER 令人信服的臨床特徵在現實世界中的表現。

Second, free goods favorability was another source of strength this quarter, reaching an average free goods share of just below 20% since ISM launch. Our free goods share has been a significant source of strength in the first half of the year as the mix of patients on AYVAKIT skews increasingly towards ISM and as the IRA Part D redesign has enabled more patients to access paid therapy.

其次，免費商品的受歡迎程度是本季的另一個成長動力，自 ISM 推出以來，免費商品的平均份額略低於 20%。我們的免費商品份額是今年上半年的重要力量來源，因為 AYVAKIT 上的患者結構越來越傾向於 ISM，而 IRA D 部分重新設計使更多患者能夠獲得付費治療。

Finally, the strong trends we have seen in our US launch are playing out in our international business. Our international team is driving strong performance with the ISM launch underway in Germany where the prescriber base is growing across both academic and community settings.

最後，我們在美國推出時看到的強勁趨勢正在我們的國際業務中反映出來。隨著 ISM 在德國的啟動，我們的國際團隊正在推動強勁的業績，德國的處方醫生群體在學術和社區環境中都在不斷增長。

And we are working AYVAKIT to market for ISN in additional countries in 2025, both through our own global footprint and through distributors. We're just getting started and expect our international business to be an important contributor to our growth going forward.

我們正在與 AYVAKIT 合作，透過我們自己的全球足跡和分銷商，於 2025 年在其他國家/地區銷售 ISN。我們才剛起步，預計我們的國際業務將為我們未來的成長做出重要貢獻。

Our year-to-date performance across key growth drivers has been strong and our conviction in this blockbuster opportunity has never been stronger. As we enter the second half of the year, we expect continued strength across the business and we're also keeping our eye on a few things like seasonality, something common across our industry that we anticipate will impact the timing of patient starts.

今年迄今為止，我們在主要成長動力方面的表現一直強勁，我們對這一重大機會的信念也從未如此堅定。隨著進入今年下半年，我們預計整個業務將持續強勁，我們還將密切關注季節性等一些因素，這是我們行業中常見的因素，我們預計這將影響患者開始治療的時間。

Our share of free goods, which we believe has stabilized and will remain at a steady rate for the remainder of the year and the revenue impact of German pricing negotiations, which should be finalized at the end of the year.

我們的免費商品份額已經穩定，並將在今年剩餘時間內保持穩定，以及德國定價談判對收入的影響，該談判應在年底敲定。

The most important part of seasonality now that we understand it better is that we don't expect it will impact annual performance. Patients are out there and it's not a question of if, but when they'll start on AYVAKIT. And once they start, we know they'll stay on for a long time. As we enter the second half of the year, we're focused on driving increased breadth and depth of prescribing and activating patients to seek treatment.

現在我們對季節性的最重要部分有了更好的理解，我們預計它不會影響年度業績。患者就在那裡，問題不是是否開始服用 AYVAKIT，而是何時開始服用 AYVAKIT。一旦他們開始，我們知道他們會持續很長時間。進入今年下半年，我們的重點是擴大處方的廣度和深度，並鼓勵患者尋求治療。

Let's look at these areas next. As I mentioned, we continue to expand the breadth and depth of the AYVAKIT prescriber base. Prescriber breadth is growing steadily across all specialties including allergy. Prescriber depth is growing as first positive experiences lead to repeat prescriptions.

接下來我們來看看這些領域。正如我所提到的，我們繼續擴大 AYVAKIT 處方者基礎的廣度和深度。包括過敏在內的所有專業的處方醫生範圍都在穩步增長。隨著第一次的正面經驗導致重複處方，處方者的深度正在不斷增長。

For the first time, this quarter, we're seeing prescribers with more than 10 patients on therapy with AYVAKIT and we see a clear trend of experienced prescribers broadening their view of who's an appropriate patient for AYVAKIT.

本季度，我們首次看到超過 10 名患者接受 AYVAKIT 治療的處方者，並且我們看到經驗豐富的處方者拓寬了他們對 AYVAKIT 合適患者的看法的明顯趨勢。

Long-term safety and efficacy data are highly motivating for providers and patients, which is why we continue to show that AYVAKIT clinical profile is durable with long-term follow-up data. This past quarter at the EAACI conference in Spain, we showed that AYVAKIT leads to deep and sustained symptom alleviation and a well-tolerated safety profile, now over multiple years of treatment.

長期安全性和有效性數據對提供者和患者俱有高度激勵性，這就是為什麼我們繼續透過長期追蹤數據證明 AYVAKIT 臨床特徵的持久性。上個季度在西班牙舉行的 EAACI 會議上，我們表明，經過多年的治療，AYVAKIT 可以深度、持續地緩解症狀，並具有良好的耐受性安全性。

The chronic burden of ISM is often underappreciated and a key part of our ongoing strategy is redefining expectations for control for patients and providers. Trying a new treatment is a big step for patients who are accustomed to managing their disease by limiting their daily activities, taking symptom directed medications and avoiding triggers.

ISM 的長期負擔常常被低估，我們持續策略的關鍵部分是重新定義對患者和提供者的控制期望。對於習慣透過限制日常活動、服用針對症狀的藥物和避免觸發因素來控制疾病的患者來說，嘗試新的治療方法是邁出的一大步。

Patients living with ISM have made a lot of compromises. Oftentimes they don't realize until after they've started AYVAKIT, how good their lives can be again. But they need to get ready to make that change.

患有 ISM 的患者做出了很多妥協。通常，他們直到開始 AYVAKIT 後才意識到，他們的生活可以再次變得多麼美好。但他們需要做好改變的準備。

What we've been hearing in this first year of launch is that we are beginning to change the experience of living with ISM. Patients are sharing that AYVAKIT is life-changing enabling them to return to work school and family activities, reducing unpredictable symptom flares and helping them feel better. And they're starting to tell each other about it. This patient-to-patient dialogue is very powerful, and we're scaling several key initiatives to enable this further.

在推出的第一年，我們聽到的是，我們正在開始改變 ISM 的生活體驗。患者表示 AYVAKIT 改變了他們的生活，使他們能夠重返工作學校和家庭活動，減少不可預測的症狀發作並幫助他們感覺更好。他們開始互相講述這件事。這種患者與患者之間的對話非常有力，我們正在擴展幾項關鍵措施以進一步實現這一目標。

Building on the success of our virtual patient educational series, we recently launched our first in-person patient ambassador program in conjunction with the Mast Cell Disease Society's Mast Cell Con last month. Throughout that meeting, it was incredible to see firsthand, the impact of patient sharing experiences with other patients.

基於我們虛擬患者教育系列的成功，我們最近與肥大細胞疾病協會的肥大細胞大會聯合推出了我們的第一個面對面患者大使計畫。在整個會議期間，我親眼目睹了患者與其他患者分享經驗的影響，這令人難以置信。

In closing, our first full year of launch has been highly successful and sets us firmly on the path to achieve a more than $2 billion opportunity for AYVAKIT. We are proud of the effort our commercial and medical teams have put forward. We understand every step of the patient journey and the education and support patients and providers need.

最後，我們的第一個全年發布非常成功，使我們堅定地走上為 AYVAKIT 實現超過 20 億美元機會的道路。我們為我們的商業和醫療團隊所做的努力感到自豪。我們了解患者旅程的每一步以及患者和提供者所需的教育和支持。

Our strategies are working and AYVAKIT is making a difference. And we see a critical mass of both provider experience and patient activation that creates a nice compounding effect and bodes well for future growth.

我們的策略正在發揮作用，AYVAKIT 正在發揮作用。我們看到提供者的經驗和患者的積極性達到了臨界點，這創造了良好的複合效應，並預示著未來的成長。

With that I'll turn it over to Christy.

這樣我就把它交給克莉絲蒂。

Thanks, Philina. In addition to the continued execution of the AYVAKIT launch, we are focused on driving the next wave of innovation and growth at Blueprint Medicines. And today, I'd like to speak briefly about progress against our 2024 portfolio milestones.

謝謝，菲莉娜。除了繼續執行 AYVAKIT 的推出外，我們還致力於推動 Blueprint Medicines 的下一波創新和成長。今天，我想簡單談談我們 2024 年投資組合里程碑的進展。

Let's start with the franchise, we are building in mast cell disorders with AYVAKIT, elenestinib and BLU-808. SM is a multibillion-dollar market opportunity and we are committed to extending our leadership position and patient impact.

讓我們從特許經營權開始，我們正在利用 AYVAKIT、elenestinib 和 BLU-808 來治療肥大細胞疾病。SM 是一個價值數十億美元的市場機會，我們致力於擴大我們的領導地位和病患影響力。

Through our engagement with physicians and patients and the unparalleled depth of clinical data and real-world experience, we have amassed, we have unique insights into the biology of SM and the next frontiers of innovation that can move us further towards our goal of eradicating this disease.

Through our engagement with physicians and patients and the unparalleled depth of clinical data and real-world experience, we have amassed, we have unique insights into the biology of SM and the next frontiers of innovation that can move us further towards our goal of eradicating this疾病.

We have been advancing elenestinib, our next-generation KIT D816 V inhibitor to the registration directed Part two of the HARBOR study. We are on track to initiate Part two of HARBOR by year end. And as we do, we will be sharing more details about our plans.

我們一直在將下一代 KIT D816 V 抑制劑 elenestinib 推進到 HARBOR 研究第二部分的註冊階段。我們預計在年底前啟動 HARBOR 第二部分。同時，我們將分享有關我們計劃的更多細節。

In addition, today, I'm happy to share that we've reached an important milestone in our efforts to bring BLU-808 our wild-type KIT inhibitor to a broad range of patients suffering from allergic and inflammatory diseases. We've moved BLU-808 into the clinic with the initiation of our healthy volunteer study and are eagerly anticipating initial data early next year.

此外，今天，我很高興與大家分享，我們在將 BLU-808 野生型 KIT 抑制劑帶給廣大患有過敏性和發炎性疾病的患者方面取得了一個重要的里程碑。隨著健康志願者研究的啟動，我們將 BLU-808 轉移到臨床，並熱切期待明年初的初步數據。

We believe this data could mark an important inflection point for the program supporting our hypothesis that we can achieve tunable biological activity with a wide therapeutic window and enabling us to rapidly establish clinical proof of concept in a range of mast cell disorders including and beyond urticaria.

我們相信，這些數據可能標誌著該計劃的一個重要轉折點，支持我們的假設，即我們可以透過廣泛的治療窗口實現可調節的生物活性，並使我們能夠在包括蕁麻疹在內的一系列肥大細胞疾病中快速建立臨床概念證明。

Our goal is to raise the bar on what a disease-modifying treatment can offer considering the full patient experience, efficacy, safety and the burden associated with administration. And we will share more about our development strategy in the second installment of our scientific webinar series planned for this fall.

我們的目標是考慮到患者的完整體驗、療效、安全性和與給藥相關的負擔，提高疾病緩解治療的標準。我們將在計劃於今年秋天舉行的科學網路研討會系列的第二期中分享更多有關我們的發展策略的資訊。

Mast cell disorders are the key pillar in our R&D strategy. And our second focus area of cell cycle inhibition, the clinical data we are generating with BLU-222 is validating the importance of CDK2 as a target and gives us conviction that the next frontier in the treatment of breast cancer is the complete inhibition of the cell cycle achieved by targeting cell cycle regulators in combination.

肥大細胞疾病是我們研發策略的關鍵支柱。我們的第二個重點領域是細胞週期抑制，我們用 BLU-222 產生的臨床數據驗證了 CDK2 作為靶標的重要性，並讓我們相信乳腺癌治療的下一個前沿是細胞的完全抑制通過組合靶向細胞週期調節劑來實現週期。

We believe that the optimal approach to bring BLU-222 forward to patients, is in the context of a partnership to maximize the transformative potential of this target and these discussions are ongoing.

我們相信，將 BLU-222 帶給患者的最佳方法是在合作關係的背景下，最大限度地發揮該目標的變革潛力，並且這些討論正在進行中。

We are also making significant progress, advancing cell cycle degraders, which are poised to represent the first development candidate out of our targeted protein degradation platform. This platform was established just a few years ago under Percy Carter's leadership and is already an integral part of our R&D engine, across both allergy inflammation and oncology.

我們也在推進細胞週期降解劑方面取得了重大進展，這些降解劑有望代表我們的目標蛋白質降解平台的第一個開發候選產品。該平台幾年前在 Percy Carter 的領導下建立，現已成為我們研發引擎不可或缺的一部分，涵蓋過敏發炎和腫瘤學領域。

With that I will turn it over to Mike.

這樣我就把它交給麥克了。

Thanks, Christy. Earlier this morning, we reported detailed financial results in our press release. And for today's call, I'll touch on a few highlights from the quarter. In the second quarter, total revenues were $138.2 million, including $114.1 million in net product revenues from sales of AYVAKIT and $24 million in collaboration license and other revenues.

謝謝，克里斯蒂。今天早些時候，我們在新聞稿中報告了詳細的財務表現。在今天的電話會議中，我將談談本季的一些亮點。第二季總收入為 1.382 億美元，其中包括 AYVAKIT 銷售帶來的 1.141 億美元產品淨收入以及 2,400 萬美元的合作許可和其他收入。

As Philina noted earlier on the call, we are raising our AYVAKIT product revenue guidance and now expect to achieve $435 million to $450 million in net product revenue in 2024. This guidance update continues to reflect our evolving view of the fundamentals driving the business, patients on therapy, including a greater understanding of the role that seasonality plays in ISM, free goods favorability and its impact on revenue growth in the second half compared to the first half of the year, continued strength in compliance and duration of therapy and the potential impact of the ISM price negotiations in Germany.

正如 Philina 早些時候在電話會議中指出的那樣，我們正在提高 AYVAKIT 產品收入指引，目前預計 2024 年產品淨收入將達到 4.35 億至 4.5 億美元。本指南更新繼續反映了我們對推動業務發展的基本面、接受治療的患者的不斷變化的看法，包括對季節性在ISM 中發揮的作用、免費商品優惠及其對下半年收入增長的影響（與上半年相比）有了更深入的了解今年上半年，依從性和治療持續時間持續強勁，以及德國 ISM 價格談判的潛在影響。

First half growth trajectory was influenced by stronger than expected performance, with upside across a combination of variables that drove results above the strong and steady growth that we have always expected.

上半年的成長軌跡受到強於預期的業績的影響，多種變數組合的上行推動業績高於我們一直預期的強勁而穩定的成長。

Throughout the year, we have talked about our philosophy in setting guidance and our goal of providing estimates that are relevant and reflective of our own expectations. We have also talked about the inherent challenges in setting guidance so early in the launch into a brand-new market that we are building.

在這一年中，我們一直在談論我們制定指導的理念以及提供與我們自己的期望相關且反映的估計的目標。我們也討論了在進入我們正在建立的全新市場的早期階段製定指導意見所面臨的固有挑戰。

I'm thrilled that our performance year to date has enabled us to raise guidance twice, and we are also now in a position to have better insight into the variables that will drive performance in the second half of the year, and the range of likely outcomes on those variables. And this is reflected in our update today.

我很高興我們今年迄今為止的業績使我們能夠兩次提高指引，而且我們現在也能夠更好地洞察將推動下半年業績的變量，以及可能的範圍這些變量的結果。這反映在我們今天的更新中。

Turning to expenses. Our total cost and operating expenses were relatively flat at $181.2 million for the second quarter and we anticipate that both our research and development expenses and our SG&A expenses will remain relatively flat for the remainder of this year.

轉向開支。第二季我們的總成本和營運費用相對持平，為 1.812 億美元，我們預計今年剩餘時間裡，我們的研發費用和銷售、一般管理費用將保持相對持平。

We remain in a solid financial position with $868.5 million in cash on hand. And with the ongoing success of the AYVAKIT launch and our commitment to manage operating expenses, we are in a great position to continue to drive long-term shareholder value.

我們的財務狀況依然穩健，手頭現金為 8.685 億美元。隨著 AYVAKIT 推出的持續成功以及我們對管理營運費用的承諾，我們處於繼續推動長期股東價值的有利位置。

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

這樣，我現在將把電話轉回給接線員詢問問題。操作員？

(Operator Instructions) Salveen Richter, Goldman Sachs.

（操作員指令）Salveen Richter，高盛。

Good morning. Thanks for taking my question here.

早安.感謝您在這裡提出我的問題。

With regard to the ISM launch here, now that your full year post approval, how are you thinking of quarterly dynamics here? And could you discuss any impact you've seen to date from the Part D redesign and how this might be evolved?

關於此處推出的 ISM，既然您已全年批准，您對此處的季度動態有何看法？您能否討論一下迄今為止您從 D 部分重新設計中看到的任何影響以及它可能如何演變？

And for your wild-type KIT, should we expect healthy volunteer data this year or early next year? And how are you thinking about the importance of this data set, as it relates to PK/PD such as potential for flexible dosing? Thank you.

對於你們的野生型 KIT，我們應該期待今年或明年初的健康志工數據嗎？您如何看待該資料集的重要性，因為它與 PK/PD（例如靈活劑量的潛力）相關？謝謝。

Thank you, Salveen. For the question, Philina, why don't you talk a little bit more about those quarterly dynamics and how we're seeing some of the Part D reform impacting that? And then Fouad, if you can talk a little bit more about the wild-type KIT, healthy volunteer data that'd be great.

謝謝你，薩爾文。對於這個問題，Philina，您為什麼不多談談這些季度動態以及我們如何看待 D 部分改革對其產生的影響？然後，Fouad，如果您能多談談野生型 KIT、健康志願者數據，那就太好了。

Hi, Salveen. First off, I think we're just really pleased with yet another strong quarter in our launch and this has strengthened our conviction to the greatest degree, I think we've ever had really to see the degree of provider feedback, the growing prescriber base and how activated patients are coming. These are the factors that will really portend towards the peak potential of AYVAKIT.

嗨，薩爾文。首先，我認為我們對我們的推出又一個強勁的季度感到非常高興，這在最大程度上增強了我們的信念，我認為我們確實看到了提供者反饋的程度以及不斷增長的處方者基礎以及患者的活躍程度如何。這些因素將真正預示著 AYVAKIT 的最大潛力。

Speaking to the quarterly dynamics, I think as we dig in and learn more about this chronic rare disease opportunity, one of the things that we're learning is to expect some seasonal dynamics right? And so for patients with chronic rare disease trying something new is really a big step and they may be more hesitant to do that around times of vacations and holidays.

談到季度動態，我認為當我們深入研究並更多地了解這種慢性罕見疾病機會時，我們正在學習的一件事就是預期一些季節性動態，對嗎？因此，對於患有慢性罕見疾病的患者來說，嘗試新事物確實是一大進步，他們在假期和假日期間可能會更加猶豫是否要這樣做。

We saw some of this dynamic last year around Q4. But more importantly is to note that the opportunity is absolutely there. The patient funnel is strong. There are a number of patients in need who are not well controlled. And it's not a question of time of if, but when they go on therapy.

去年第四季左右，我們看到了一些這種動態。但更重要的是要注意，機會是絕對存在的。患者漏斗很強大。還有不少有需要的患者沒有得到很好的控制。這不是時間問題，而是他們何時接受治療的問題。

The timing of when they start depends on a few things. We talked about seasonal impacts. We talked about and the timing of when they happen to have patient visits. Another component that's important is how they're feeling when they show up at that visit which impacts the provider's ability to recognize their -- the disease burden.

他們開始的時間取決於一些因素。我們討論了季節性影響。我們討論了他們碰巧拜訪病人的時間。另一個重要的組成部分是他們在就診時的感受，這會影響提供者認識到他們的疾病負擔的能力。

And so importantly, the opportunity is absolutely there. It's not a question of if but when. If a patient doesn't start in August, they will likely started a subsequent visit. And when they start we know they'll stay on AYVAKIT. These are the most important factors that give us confidence in that peak opportunity.

更重要的是，機會絕對存在。這不是是否的問題，而是何時的問題。如果患者沒有在八月開始就診，他們可能會開始後續就診。當他們開始時，我們知道他們會留在 AYVAKIT。這些是讓我們對這個高峰機會充滿信心的最重要因素。

To your question about Part D redesign, we've highlighted the proportion of free goods as one of the important fundamentals in our launch. And that with the strong execution of our team, we've been able to convert a number of patients over to access commercial therapy.

對於您有關 D 部分重新設計的問題，我們強調免費商品的比例是我們發布的重要基礎之一。憑藉我們團隊的強大執行力，我們已經能夠使許多患者轉而接受商業治療。

We believe at this point that the proportion of free goods has stabilized. We've reached just under 20% on average launch to date, and we expect this to remain relatively stable for the rest of the year.

我們認為目前免費商品的比例已經穩定。迄今為止，我們的平均發布率已達到略低於 20%，我們預計這一數字在今年剩餘時間內將保持相對穩定。

Maybe just one thing to add on that Salveen is that, as we think about ISM really this is much more of an I&I type of footprint in terms of payer mix. These patients tend to skew younger have more commercial payer. And so that's obviously part of that favorability that we're seeing as well. So I'm going to move on to BLU-808?

也許 Salveen 需要補充的一件事是，當我們考慮 ISM 時，就付款人組合而言，這實際上更像是一種 I&I 類型的足跡。這些患者往往更年輕，擁有更多的商業付款人。因此，這顯然也是我們所看到的好感度的一部分。那我要轉向 BLU-808 嗎？

Yeah. Thank you, Kate and Salveen. So I'm very, very happy that the FDA review process IND was very smooth and that now the healthy volunteers study is up and running. We expect the SADMAT data to be available early in 2025.Aand it is an important milestone, an important inflection point for us to show the PK the PD and the safety data in healthy volunteers.

是的。謝謝凱特和薩爾文。所以我非常非常高興 FDA 的 IND 審查過程非常順利，現在健康志願者研究已經啟動並運行。我們預計 SADMAT 數據將於 2025 年初提供。

We all know wild-type KIT as a target in chronic spontaneous urticaria or CSU now in cold-induced urticaria has been already demonstrated. So showing good profile is consistent with our expectations from 808 will be really a major inflection point for us. So that data will be very important early next year.

我們都知道野生型 KIT 作為慢性自發性蕁麻疹或 CSU 的靶標，目前在寒冷誘發的蕁麻疹中已經得到證實。因此，表現出良好的形象符合我們對 808 的期望，這對我們來說確實是一個重大轉折點。因此，這些數據明年初將非常重要。

Brad Canino, Stifel.

布拉德·卡尼諾，斯蒂菲爾。

Thank you. Nice quarter. One of the main discussions I still have is around how to think about the right eligibility proportion for AYVAKIT. And there is this thesis and you even talked about this that this number is likely dynamic over time where you might see there is a threshold for use around disease severity declines with physician experience.

謝謝。不錯的季度。我仍然在討論的主要問題之一是如何考慮 AYVAKIT 的正確資格比例。有這篇論文，您甚至談到這個數字可能會隨著時間的推移而動態變化，您可能會發現隨著醫生經驗的增加，疾病嚴重程度下降存在一個使用閾值。

So I'm looking at this and you now have initial practices that have been installed for a year. You're highlighting that many of the practices have up to 10 or more patients on therapy. So I want to ask what is your initial read?

所以我正在研究這個，你現在已經有了已經安裝了一年的初步實踐。您強調，許多診所都有多達 10 名或更多的患者接受治療。所以我想問你最初讀的是什麼？

What are you seeing on the ground of the type of patient that's starting therapy today at those legacy practices where there is good AYVAKIT experience? And what is your vision for where this eligibility number goes long term? Thank you.

對於今天在那些擁有良好 AYVAKIT 經驗的傳統診所開始治療的患者類型，您有何看法？您對這個資格數字的長期發展有何願景？謝謝。

Thank you, Brad for that question. And it's a great question. As we really do see this as a growing overall pie. Philina, do you want to talk a little bit more about that?

謝謝布拉德提出這個問題。這是一個很好的問題。我們確實認為這是一個不斷增長的整體蛋糕。菲莉娜，你想再談這個嗎？

Yeah. Thanks Brad. I think your hypothesis is really on point, and we really do see a trend towards providers with that first positive experience on AYVAKIT where they're likely to select the one or two most symptomatic patients within their practice.

是的。謝謝布拉德。我認為你的假設確實是正確的，我們確實看到了一種趨勢，即在 AYVAKIT 上獲得第一次積極體驗的醫療服務提供者可能會在他們的實踐中選擇一兩個症狀最嚴重的患者。

We are really seeing a trend towards them broadening the lens on who's an appropriate patient for AYVAKIT towards patients who may have one or two predominant symptoms that are significantly impacting their quality of life.

我們確實看到了一種趨勢，他們將誰是 AYVAKIT 的合適患者的範圍擴大到可能具有一兩種顯著影響其生活品質的主要症狀的患者。

Having interacted with a number of these providers firsthand and through our field intelligence, we see multiple signs of that deepening and we also see it reflected in our claims data as we look at the degree of symptom burden ER visits and other measures of disease severity.

透過我們的現場情報與許多此類提供者進行第一手互動後，我們看到了這種加深的多種跡象，並且當我們查看急診室就診的症狀負擔程度和疾病嚴重程度的其他衡量標準時，我們也看到它反映在我們的索賠數據中。

What we're starting to see is a real trend towards that broadening lens of providers opening their minds to who's eligible for AYVAKIT. And so we think that portends very well towards us achieving the peak opportunity.

我們開始看到一種真正的趨勢，即醫療服務提供者的視角不斷擴大，他們對誰有資格獲得 AYVAKIT 持開放態度。因此，我們認為這預示著我們將獲得最大的機會。

Yeah. And maybe just add on to that Brad, a couple of things. One to Philinia's point, really almost every SM patient United States is eligible for AYVAKIT. And we have such a broad label.

是的。也許只是補充一下布拉德的一些事情。Philinia 指出，實際上幾乎所有美國 SM 患者都有資格接受 AYVAKIT。我們有一個如此廣泛的標籤。

And I think to Philinia's point what we're seeing is that both prescribers and patients are widening their lens on the benefits of treatment, which increasingly we're beginning to understand go beyond just sort of resolution of symptoms, but really addressing some of the underlying drivers of the disease that we think could have longer-term implications for these patients.

我認為，就菲利尼亞的觀點而言，我們看到的是，處方者和患者都在擴大對治療益處的認識，我們越來越多地開始理解，這不僅僅是解決症狀，而是真正解決一些問題。 我們認為疾病的潛在驅動因素可能會對這些患者產生長期影響。

The other really interesting aspect of this market is sort of our increasing understanding that the prevalence may actually be underestimated and may be growing, right? So we know that the number of diagnosed patients has been growing over time.

這個市場的另一個真正有趣的方面是我們越來越多地認識到流行率實際上可能被低估並且可能正在增長，對嗎？所以我們知道，隨著時間的推移，確診患者的數量一直在增加。

There's also increasingly data out there that suggests that the true prevalence of the disease could be twice what we thought it was. So I think the dynamics are really interesting and how they will play out to drive what ultimately could be a peak potential that's even greater than what we've estimated to-date.

越來越多的數據表明，這種疾病的真實盛行率可能是我們想像的兩倍。因此，我認為這些動態非常有趣，以及它們將如何發揮作用，最終推動峰值潛力，甚至比我們迄今為止估計的還要大。

Marc Frahm, TD Cowen.

馬克·弗拉姆，TD·考恩。

Thanks for taking my questions. Congrats on another strong quarter for AYVAKIT. Maybe over the last few quarters investment year or so AYVAKIT have been growing like $15 million, $20 million a quarter at least. Just your guidance seems to assume quite a significant slowdown from that I guess. And then all the commentary around your huge patient population still to access and everything would be kind of pointing to the opposite.

感謝您回答我的問題。恭喜 AYVAKIT 又一個強勁的季度。也許在過去幾季的投資年中，AYVAKIT 的成長幅度約為 1,500 萬美元，至少每季 2,000 萬美元。僅您的指導似乎就假設了我猜測的顯著放緩。然後，圍繞龐大患者群體的所有評論仍然有待訪問，一切都將指向相反的方向。

I guess is there some sort of dynamic beyond just maybe people pushing out a month or two start because of summer vacations that is driving that? Was there some sort of stocking impact in Q2 or something else, we should be thinking about?

我想除了人們因為暑假而推遲一兩個月的開始時間之外，是否還有某種動力推動了這一點？我們應該考慮第二季是否存在某種庫存影響或其他影響？

And then maybe longer term to the last point of Christy is that maybe this opportunity is even bigger than$ 2 billion. I guess what do you need to see to what needs to happen to kind of give you confidence that is $2.5 billion or $3 billion or something bigger than $2 billion?

從長遠來看，克里斯蒂最後一點是，這個機會可能比 20 億美元還要大。我想你需要看到什麼才能給你 25 億美元或 30 億美元或超過 20 億美元的信心？

Yeah. Thank you Mark for the question. Philina, do you want to talk a little bit about how we've considered the range of variables that inform guidance? I mean, maybe I'll just clarify very quickly. There is no stocking impact, MarK. We actually -- as we've mentioned this on some other calls where we actually have kind of guidance and contractual guidelines within our channel that doesn't allow for that. But maybe Philina you can talk a little bit more about how we're thinking about guidance, those range of variables.

是的。謝謝馬克提出的問題。Philina，您想談談我們如何考慮指導指導的變數範圍嗎？我的意思是，也許我會很快澄清。沒有庫存影響，Mark。實際上，正如我們在其他一些電話中提到的那樣，我們的管道內實際上有某種指導和合約準則，不允許這樣做。但也許菲利娜，你可以多談談我們如何考慮指導，這些變數的範圍。

Yeah. And I think maybe first off, Mark to your question about what do we need to see. I think it's exactly what we're seeing, which is giving us that conviction in the peak opportunity and that we're marching along the path to achieve that peak.

是的。我想也許首先請回答你的問題，即我們需要看到什麼。我認為這正是我們所看到的，這讓我們對巔峰機會充滿信心，並且我們正在沿著實現巔峰的道路前進。

I think it's valuable to sort of look to where we started this year and where we are now at the midpoint where our updated guidance represents a more than doubling and of our revenue over last year.

我認為，看看我們今年的起點和現在的中點是有價值的，更新後的指導代表我們的收入比去年增加了一倍多。

To your question, more about the dynamics and the growth rate so certainly, I think the guidance provides the best signpost for the continued growth. As I've alluded to this represents substantial revenue growth year-over-year.

對於你的問題，更多關於動態和成長率，所以當然，我認為該指導為持續成長提供了最好的路標。正如我所提到的，這代表著收入同比大幅增長。

The guidance factors in a number of variables. And so we've talked about how it's patients on therapy which is a function both of new patient starts and discontinuation rates which have been very low attending chronic durations of therapy.

此指導因素考慮了許多變數。因此，我們已經討論了患者如何接受治療，這是新患者開始治療和停藥率的函數，在長期治療期間，停藥率非常低。

I think we've spoken a couple of times to the potential for seasonal impacts and which we wouldn't be surprised to see around the times of the holidays. But importantly is that even if quarter-over-quarter is variable. It's the year-over-year that remains strong and puts us marching towards that impact.

我想我們已經多次討論過季節性影響的可能性，如果在假期期間看到這種影響，我們不會感到驚訝。但重要的是，即使季度環比有所變化。正是逐年保持強勁，使我們朝著這種影響邁進。

Other factors that are important, we talked about the proportion of free goods compliance and international where we certainly see potential growth and contribution there from our expanding geographic contribution.

其他重要因素，我們討論了免費商品合規性和國際性的比例，我們當然看到了我們不斷擴大的地域貢獻帶來的潛在成長和貢獻。

Yeah. Thanks Mark. I just to reiterate what Philina said. First of all, just on the sort of dynamics. I think we've had these conversations as we've talked about guidance for the year and how we think about quarter-on-quarter dynamics.

是的。謝謝馬克。我只是重申菲莉娜所說的話。首先，就動態而言。我認為我們已經進行了這些對話，因為我們討論了今年的指導以及我們如何看待季度環比動態。

This launch is not about sort of one quarter versus the next. It's about sort of the journey that we're on towards this incredible peak opportunity. And I think what this year has demonstrated is that we are -- that opportunity is absolutely there. We are we are capturing it.

這次發布並不是一個季度與下一個季度的比較。這是我們邁向這個令人難以置信的巔峰機會的旅程。我認為今年已經證明了我們——機會絕對存在。我們正在捕捉它。

And then big picture, we're in a place where we started the year with a guide of $3.60 to $3.90 and we've raised substantially, right. So we really are very pleased with where we are right now and what that portends for future growth.

從大局來看，我們今年年初的指導價為 3.60 美元至 3.90 美元，我們已經籌集了大量資金，對吧。因此，我們對我們現在的處境以及這對未來成長的預示感到非常滿意。

In terms of what we need to see to raise the peak we have been strong in our conviction. I mean, I have seen this as a blockbuster opportunity going back to 2019. I think, we have been on a journey of building a market that from scratch really.

就我們需要看到什麼來達到頂峰而言，我們的信念一直很堅定。我的意思是，早在 2019 年我就認為這是一個巨大的機會。我認為，我們一直在從頭開始建立一個市場。

And so I think, we're bringing everybody along with us, as we demonstrate that a market opportunity is really there. We'll raise the peak as we feel it is meaningful to kind of bring everybody along and as we continue to execute the launch and really show that opportunity is there. But some of the things we're going to be looking at are exactly the dynamics definitely that philina said right that broadening of the lens on who may be an appropriate patient to treat.

所以我認為，我們正在讓所有人加入我們，因為我們證明市場機會確實存在。我們將提高峰值，因為我們認為讓每個人都參與其中是有意義的，並且隨著我們繼續執行發布並真正表明機會就在那裡。但我們要關注的一些事情正是菲利納所說的正確的動態，擴大了對誰可能是合適治療患者的視野。

The continued growth in diagnosed patients where suddenly we're seeing the number of diagnosed patients, the United States approach our initial estimates of what the actual prevalence of the disease. It would not surprise me to be in a place where we could see more patients diagnosed than the 32,000 estimate that we had at launch.

確診患者的持續成長，我們突然看到美國確診患者的數量接近我們對該疾病實際盛行率的初步估計。如果我們看到的確診患者數量比啟動時估計的 32,000 名患者還要多，我並不感到驚訝。

And so I think we'll continue to look at those dynamics, but this is really one of the most exciting launch opportunities that I've had a chance to experience in my career where you have the first disease-modifying therapy and a really serious prevalence rare disease.

因此，我認為我們將繼續關注這些動態，但這確實是我在職業生涯中經歷過的最令人興奮的啟動機會之一，您將獲得第一個疾病緩解療法和一個真正嚴肅的治療機會。罕見疾病的流行。

Michael Schmidt, Guggenheim.

邁克爾·施密特，古根漢。

Yeah. Hey guys. Good morning. Congrats from me as well on a great continued AYVAKIT launch here. Just one more on that. So uou mentioned obviously treatment duration being one very important growth driver here. And so when you think about patients what do you seeing in terms of patients that are using the drug continuously versus perhaps in a more intermittent way? And what are you seeing for refill rate and how you're thinking about that dynamic longer term ultimately?

是的。嘿夥計們。早安.我也祝賀 AYVAKIT 在這裡繼續精彩發布。就這一點還有一點。因此，您顯然提到治療持續時間是一個非常重要的成長動力。因此，當您考慮患者時，您對連續使用該藥物與間歇性使用該藥物的患者有何看法？您對補充率有何看法？

Philina do you may want to talk a little more about compliance and kind of how we're seeing patients continue on therapy here?

Philina，您想多談談依從性以及我們如何看待病人繼續在這裡接受治療嗎？

Yeah. Thanks for the question, Michael. We're really pleased to see that that strong profile of AYVAKIT from PIONEER is playing out exactly as we hoped in the real world. I mean, I think we've shared earlier that advanced SM duration of therapy is now trending to 25 months and longer.

是的。謝謝你的提問，麥可。我們非常高興看到 PIONEER 的 AYVAKIT 強大形像在現實世界中完全按照我們的希望發揮出來。我的意思是，我想我們之前已經分享過，高級 SM 治療持續時間現在趨向於 25 個月甚至更長。

If we look at our ISM trends relative to that of patients who have started on therapy are trending towards an even longer duration of therapy with very few discontinuations consistent with a multiyear chronic duration of therapy in the real world.

如果我們觀察相對於已開始治療的患者的 ISM 趨勢，就會發現治療持續時間更長，很少有中斷治療，這與現實世界中的多年慢性治療持續時間一致。

To your question on compliance again, I think really pleased to see how high compliance remains in the real world certainly towards the upper bound of analogs that we have seen. And we're really pleased to see all these impacts. We think as Kate alluded to, this is going to become increasingly important contribution to our growth as we march towards that peak opportunity.

對於你再次提出的關於合規性的問題，我認為很高興看到現實世界中的合規性有多高，當然也達到了我們所看到的類似物的上限。我們非常高興看到所有這些影響。我們認為，正如凱特所提到的，隨著我們邁向高峰機會，這將對我們的成長做出越來越重要的貢獻。

Reni Benjamin, JMP.

雷尼·本傑明，JMP。

Hey, good morning, guys. Thanks for taking the questions, and congratulations on an amazing quarter and an update of guidance. Maybe for us just the top 400 or 450 docs that you're originally targeting, how many are prescribing? And is the idea to get all of them to kind of 10 plus patients? Or is there kind of a strategy to also start expanding beyond the original number of targeted physicians as you go through this launch.

嘿，早上好，夥計們。感謝您提出問題，並祝賀您度過了一個精彩的季度並更新了指導意見。也許對我們來說，您最初的目標只是前 400 名或 450 名醫生，有多少是開處方的？是不是要把這些都提供給 10 名以上的患者？或者是否有某種策略可以在您完成此次發佈時開始擴大目標醫生的原始數量。

Yeah. Thanks for that question, Reni. And Philina, you want to talk a little bit more about the strength we've seen in the breadth and depth here and physicians adopting AYVA?

是的。謝謝你提出這個問題，雷尼。Philina，您想多談談我們在這裡看到的廣度和深度的優勢以及採用 AYVA 的醫生嗎？

Yeah, Reni maybe just to be clear our adoption and our breadth has been tremendous launch to date and continues to grow. It's certainly not limited towards just the top 400 providers by volume. That top 400 snapshot I think is most important to illustrate the dynamics of deepening that we've talked about. And we're really pleased to see that are now providers who are treating more than 10 ISM patients. I think, we would expect to continue to see deepening among those top 400.

是的，Reni 也許只是為了明確我們的採用情況和我們的廣度，迄今為止已經推出了巨大的產品，並且還在繼續增長。當然，它不僅限於數量排名前 400 名的提供者。我認為前 400 名快照對於說明我們所討論的深化動態最為重要。我們非常高興地看到這些提供者現在正在治療 10 多名 ISM 患者。我認為，我們預計前 400 名的排名將繼續加深。

But importantly, the breadth and depth that we're seeing is far more expansive beyond this. We see a growing number of hematologists oncologists, allergists in the academic and community settings, who are adopting AYVAKIT.

但重要的是，我們所看到的廣度和深度遠不止於此。我們看到越來越多的學術和社區環境中的血液學家、腫瘤學家、過敏症專家正在採用 AYVAKIT。

And in fact, we also see these dynamics of deepening happening across that entire tranche of providers who are prescribing, which we think just really reflects again the strength of the profile in the real world and how providers can become comfortable with AYVAKIT and putting those repeat patients on therapy over time.

事實上，我們也看到了正在開處方的整批提供者中發生的這些深化動態，我們認為這再次真正反映了現實世界中的實力，以及提供者如何適應 AYVAKIT 並重複這些內容患者隨著時間的推移接受治療。

Laura Prendergast, Raymond James.

勞拉·普倫德加斯特，雷蒙德·詹姆斯。

Hey guys, congrats on a great quarter. Two quick ones from me. First, what -- I know they're obviously low, but what are the railroad discontinuation rates of AYVAKIT shaking out to be? And then for 808, how much of that clinical development fits into your financial into your guidance or financial self-sustainability assuming once you have the healthy volunteer data you'll probably want to move pretty rapidly into a Phase II for CSU and possibly other indications?

嘿夥計們，恭喜您度過了一個精彩的季度。我的兩個快的。首先，我知道它們顯然很低，但是 AYVAKIT 的鐵路停運率是多少？然後對於 808，臨床開發在多大程度上適合您的財務指導或財務自我可持續性，假設一旦您擁有健康的志願者數據，您可能希望快速進入 CSU 的第二階段以及可能的其他適應症？

Yeah. Thanks for that question, Laura. Maybe Philina can you just comment on the discontinuation? And then Michael you take that question about how much we have allocated to wild-type KIT. So let's go.

是的。謝謝你提出這個問題，蘿拉。也許菲莉娜你能就停產發表評論嗎？然後麥可問了我們為野生型 KIT 分配了多少資金的問題。那我們走吧。

Yeah, Laura, I think as we've alluded to the -- in the real world discontinuation rates that we're seeing are very low, right? So once patients start on therapy they're staying on therapy. They're doing that in a highly compliant way. I mean, these are patients who have a very sticky preference.

是的，勞拉，我認為正如我們所提到的——在現實世界中，我們看到的停藥率非常低，對吧？因此，一旦患者開始接受治療，他們就會繼續接受治療。他們以高度合規的方式做到這一點。我的意思是，這些患者有非常黏性的偏好。

I think when it comes to really balancing all the things that they're doing in their lives to gain control over their disease, which includes both the behaviors that they're taking to avoid triggers as well as how they're taking medications. It turns out this an extremely compliant patient population.

我認為，當真正平衡他們在生活中為控制疾病所做的所有事情時，其中包括他們為避免觸發因素而採取的行為以及他們如何服用藥物。事實證明，這是一個非常順從的患者群體。

And so mapping that over to some of the data I alluded to in EAACI where we presented just strong and sustained symptom alleviation, sustained QOL benefit as well as a very well-tolerated safety profile that was seen over a median of two years and with patients on therapy as long as four years and ongoing. And so we absolutely expect this profile to be playing out in the real world as well.

因此，將其映射到我在EAACI 中提到的一些數據，其中我們展示了強烈且持續的症狀緩解、持續的QOL 益處以及在中位數兩年的時間裡在患者中觀察到的非常耐受的安全性。因此，我們絕對希望這個配置文件也能在現實世界中發揮作用。

And, Mike, can you talk a little bit about wild-type KIT.

Mike，您能談談野生型 KIT 嗎？

Yeah. And then just with respect to kind of our financial guidance so to answer your questions Laura, yes like on the development plan for wild-type KIT is baked into our guidance that we gave about our confidence to be able to get to a self-sustaining financial profile.

是的。然後就我們的財務指導而言，勞拉，是的，就像野生型 KIT 的開發計劃已納入我們的指導中，我們有信心能夠實現自我維持財務概況。

Our priorities as we look beyond AYVAKIT are to continue to allocate capital to high value R&D opportunities like BLU-808 that are going to drive our long term growth rate. And so that is factored in. And obviously, we'll share more color on specific financial guidance as we get into that trial and see how the data plays out.

當我們放眼 AYVAKIT 之外時，我們的首要任務是繼續將資金分配給 BLU-808 等高價值研發機會，這將推動我們的長期成長率。所以這是考慮在內的。顯然，當我們進入試驗並查看數據如何發揮作用時，我們將分享更多有關具體財務指導的資訊。

And to your point, Laura, I mean, with a really strong proof of concept that targeting KIT impacts core biology of disease that we've seen and that we believe it's really potentially the most promising way to improve patient symptoms and outcomes across a range of diseases. We're very excited about this BLU-808 program. And as we said, I think this that healthy volunteer data will be a significant inflection point for us, hat will help us think about how broad do we think that this molecule could go. And that we'll certainly look at that data to define. We have it as an absolute priority for investment, as Mike said, and we will consider even going beyond that as we anticipate this data to be very strong.

Laura，就你的觀點而言，我的意思是，有一個非常有力的概念證明，即靶向KIT 會影響我們所看到的疾病的核心生物學，並且我們相信這確實是改善患者症狀和結果的最有希望的方法。我們對這個 BLU-808 計劃感到非常興奮。正如我們所說，我認為健康志工數據對我們來說將是一個重要的轉捩點，這將幫助我們思考這種分子的應用範圍有多大。我們肯定會查看這些數據來定義。正如麥克所說，我們將其作為投資的絕對優先事項，我們甚至會考慮超越這一點，因為我們預計該數據將非常強勁。

Mike Ulz, Morgan Stanley.

麥克烏爾茲，摩根士丹利。

Hi, this is [Ryan] on for Mike Ulz. Thanks for taking our questions. On the ex-US front, you mentioned expanding AYVAKIT to additional countries in 2025. Can you just talk about the opportunity and expectations there?

大家好，我是 Mike Ulz 的 [Ryan]。感謝您回答我們的問題。在美國以外的地區，您提到 2025 年將 AYVAKIT 擴展到其他國家。您能談談那裡的機會和期望嗎？

Yeah. Thanks Mike. Christy, do you want to talk about our international expansions?

是的。謝謝邁克。克里斯蒂，您想談談我們的國際擴張嗎？

Yeah. So we are really pleased with what we're seeing from our international business. We had a great quarter this quarter. And importantly, we're really in the beginning stages of bringing AYVAKIT to patients globally and expect this to be a continued driver of top-line revenue growth as we go forward from here.

是的。因此，我們對國際業務所看到的情況感到非常滿意。本季我們度過了一個很棒的季度。重要的是，我們確實處於將 AYVAKIT 帶給全球患者的起步階段，並預計隨著我們的前進，這將成為營收成長的持續驅動力。

The nature of the business outside the US is that often pricing reimbursement is sort of a gating factor. And so launches tend to lag what we see in the United States. So what we're seeing right now is primarily Germany launching in ISM, but a number of other markets continuing to launch in advanced SM.

美國以外的業務的本質是，定價報銷通常是一個限制因素。因此，發布往往落後於我們在美國看到的情況。因此，我們現在看到的主要是德國在 ISM 中推出，但許多其他市場繼續在高級 SM 中推出。

We have a footprint throughout Europe. We also bring AYVAKIT to patients through distributors in Eastern Europe and other geographies. And so we have a great opportunity to continue to expand our revenue base.

我們的足跡遍佈歐洲。我們也透過東歐和其他地區的經銷商將 AYVAKIT 帶給患者。因此，我們有很好的機會繼續擴大我們的收入基礎。

I'd expect ISM launches to start to come online next year, primarily in some of the other major markets beyond Germany, where we're actively engaged in pricing and reimbursement procedures and sort of walking through that process now.

我預計 ISM 的發布將於明年開始上線，主要是在德國以外的其他一些主要市場，我們正在積極參與定價和報銷程序，並且現在正在逐步完成該流程。

So we would expect as those come online, we'll be able to start to commercialize in the larger ISM opportunity. So bottom-line is continue to expect that to be an important driver of growth and is certainly a contributor to that peak potential that we see for AYVAKIT globally.

因此，我們預計，隨著這些產品上線，我們將能夠開始在更大的 ISM 機會中商業化。因此，最重要的是，我們繼續期望這將成為成長的重要驅動力，並且肯定會為我們在全球範圍內看到的 AYVAKIT 峰值潛力做出貢獻。

Thank you.

謝謝。

Ami Fadia, Needham.

阿米法迪亞，尼達姆。

Good morning. Thanks for taking my question. I have two questions, one for Philina and just a follow-up to Brad's question from earlier. Can you talk through the spectrum of severity of patients across the 32,000-plus patients?

早安.感謝您提出我的問題。我有兩個問題，一個是問菲莉娜的，另一個是布拉德早些時候提出的問題的後續問題。能否詳細介紹一下 32,000 多名患者的嚴重程度？

And is there a way to in some way objectively quantify and map these patients in terms of sort of that decreasing sort of threshold for treatment? You've sort of done your patient activation efforts and gotten feedback from physicians. What's sort of your current thinking around that?

有沒有一種方法可以以某種方式客觀地量化和繪製這些患者，以降低治療閾值？您已經完成了患者激活工作並獲得了醫生的回饋。您目前對此有何想法？

And then I have another one for Becker.

然後我還有另一封信要送給貝克爾。

Please go ahead with your second question, Ami because we'll shut the line after.

阿米，請繼續回答你的第二個問題，因為我們稍後會掛斷電話。

Sounds good. Just with regards to BLU-808, is there some sort of a biomarker or a metric that we should be looking for in order to understand the breadth of application of the data from the healthy volunteer study that will read out next year? Thanks.

聽起來不錯。就 BLU-808 而言，我們是否應該尋找某種生物標記或指標，以便了解明年將發表的健康志願者研究數據的應用廣度？謝謝。

Thanks Ami. So Philina, I think the first question around the spectrum of kind of disease burden that we're seeing as patients are coming on AYVAKIT and how we think about that.

謝謝阿米。Philina，我認為第一個問題是關於我們在接受 AYVAKIT 治療的患者中看到的一系列疾病負擔以及我們如何看待這個問題。

An then for BLU-808, Fouad, you would talk a little bit about how we're how we're going to be looking at target engagement in the healthy volunteer study?

那麼對於 BLU-808，Fouad，您會談談我們將如何看待健康志願者研究中的目標參與？

Yeah. Thanks for the question Ami. I think as Christy alluded to given the breadth of the label, virtually all patients who are adults living with ISM are eligible for AYVAKIT. And certainly, I think the dynamic we're seeing playing out in our launch to date is really starting with patients who tend to be on the more severe end of symptomology, but broadening towards an ever-widening lens and on who is an appropriate patient.

是的。謝謝阿米的提問。我認為，正如 Christy 所提到的，考慮到標籤的廣泛性，幾乎所有患有 ISM 的成年患者都有資格接受 AYVAKIT。當然，我認為我們在迄今為止的發布中所看到的動態實際上是從那些往往症狀更嚴重的患者開始的，但逐漸擴大到一個不斷擴大的視角以及誰是合適的患者。

And we're seeing that I think both on the provider side as they gain experience as well as on the patient side as patients who were on that step is considering AYVAKIT are encountering more of their providers gaining that experience, having comfort managing AYVAKIT and identifying I have an opportunity to address these one or two symptoms that are really impacting my quality of life.

我們看到，我認為無論是在提供者方面，因為他們獲得了經驗，還是在患者方面，因為正在考慮AYVAKIT 的患者都遇到了更多的提供者獲得了這種經驗，能夠舒適地管理AYVAKIT 並辨識我有機會解決真正影響我生活品質的一兩個症狀。

I think importantly just the way we think about ISM two is really it's not just a static disease. It's not necessarily even just treating the symptoms that's important. This is a disease where you have cumene mast cells, too many abnormal or mutated mast cells in the bone marrow and other organs of the body that's leading to worsening of symptoms over time, that's leading progressively to impacts on bone health and other elements of the biology, that's leading to the potential for progression.

我認為重要的是，我們對 ISM 2 的思考方式其實不僅僅是一種靜態疾病。僅僅治療症狀並不一定很重要。這是一種異丙苯肥大細胞疾病，骨髓和身體其他器官中存在過多異常或突變的肥大細胞，隨著時間的推移，症狀會惡化，逐漸對骨骼健康和身體其他因素產生影響。 ，這導致了進步的潛力。

And so I think one piece we're also seeing on the leading edge with key opinion leaders is really that urgency to treat ISM in an attempt to improve that natural history of the disease.

因此，我認為我們在關鍵意見領袖中看到的最前沿的一篇文章確實是治療 ISM 的緊迫性，以試圖改善疾病的自然史。

Maybe just add one thing Ami, is at the beginning of this year, we did have as we look at claims data which Christy already could have talked through how we believe that that's likely an undercall of what the overall disease prevalence is.

也許只是補充一件事，阿米，在今年年初，當我們查看索賠數據時，克里斯蒂已經可以談論我們如何相信這可能低估了整體疾病流行率。

But we said there's just about a little under 10,000 patients who would qualify as moderate to severe. So those are patients that are kind of right in line with our PIONEER clinical trial.

但我們說大約有不到 10,000 名患者符合中度至重度的標準。這些患者與我們的 PIONEER 臨床試驗相符。

And so if you think about 10,000, there plus this broadening aperture, really we are just scratching the surface of this opportunity and there're thousands of patients who could potentially benefit from AYVAKIT, which again leads to our conviction on this peak opportunity.

因此，如果你考慮10,000 名患者，再加上不斷擴大的光圈，實際上我們只是觸及了這個機會的表面，還有成千上萬的患者可能會從AYVAKIT 中受益，這再次讓我們對這個高峰機會充滿信心。

Fouad do you want to talk little bit about BLU-808.

您想談談 BLU-808 嗎？

Hey Ami, for BLU-808 and the data that we'll see from healthy volunteers will cover obviously the safety which is important, but also the pharmacology and pharmacodynamics. And we're looking at a wide number of pharmacodynamic markers in the healthy volunteer study.

嘿，Ami，對於 BLU-808，我們將從健康志願者那裡看到的數據顯然將涵蓋重要的安全性，但也涵蓋藥理學和藥效學。我們正在健康志願者研究中研究大量藥效學標記。

As we all know when we talked about it at our past webinar a few months ago, wild-type KIT as a target is really an ideal target to tackle type two inflammation or inflammatory diseases and the range of applicability is a pretty broad.

眾所周知，當我們在幾個月前的網路研討會上談到這一點時，野生型KIT作為靶點確實是解決二型發炎或發炎性疾病的理想靶點，並且適用範圍相當廣泛。

The way we are thinking about it the way we are tackling that and increasing our confidence in the opportunity for BLU-808 is really not looking at biomarker, but rapidly looking at clinical -- multiple clinical proof of concept as we finish the execution of the very early study that we just started. That will give us even an idea on the breadth of the diseases with type two inflammation diseases that we will go to with the BLU-808.

我們思考這個問題的方式，我們解決這個問題的方式，以及增強我們對BLU-808 機會的信心的方式，實際上並不是著眼於生物標誌物，而是在我們完成執行項目時快速著眼於臨床— —多個臨床概念驗證。這甚至可以讓我們了解 BLU-808 所涉及的二型發炎疾病的範圍。

Matt Biegler, Oppenheimer.

馬特·比格勒，奧本海默。

Hey, good morning guys. Congrats on the front from us as well. Can you comment on whether there's been any net pricing increases quarter-over-quarter? And if so, could you break down revenue growth by price versus volumes is a question that a few investors have asked us. Thanks.

嘿，早上好，夥計們。我們也對前面的情況表示祝賀。您能否評論一下淨定價是否比上一季有所成長？如果是這樣，您是否可以按價格與銷售來細分收入成長，這是一些投資者問我們的問題。謝謝。

Thanks for the question, Matt. I think that's an easy one. I can just take that. But no we have not had any quarter-over-quarter net pricing increases. So that's not that's not one of the contributing factors.

謝謝你的提問，馬特。我認為這是一件容易的事。我可以接受。但我們並沒有出現任何季度環比的淨定價上漲。所以這並不是促成因素之一。

Thank you.

謝謝。

David Lebowitz, Citi.

大衛‧勒博維茨，花旗銀行。

Hi. John on for David. Thanks for taking our question. On AYVAKIT can you contextualize some of the trends you're seeing for prescribers at academic centers versus community centers? And in the slides, it appears that the relative proportion of community docs has ticked slightly down from the last quarter. So just any color there would be helpful. Thanks.

你好。約翰替補大衛。感謝您提出我們的問題。在 AYVAKIT 上，您能否將您所看到的學術中心與社區中心的處方醫生的一些趨勢結合起來？在幻燈片中，社群文件的相對比例似乎比上季略有下降。所以任何顏色都會有幫助。謝謝。

Yeah, John, thanks for the question. I think one of the things that we've been really pleased about is the participation of the community so early even in the first quarter of our launch. But Philina do want to talk a bit more about that split?

是的，約翰，謝謝你的提問。我認為我們真正感到高興的一件事是，即使在我們發布的第一季度，社區也這麼早就參與了。但菲莉娜確實想多談談這次分手嗎？

Yeah sure. So as Kate alluded to, I think really the breadth of prescribing is one of the most important lead indicators in a chronic rare disease launch like this one. We see that as a great sort of lead for continued growth and prescribing. The trends that you're speaking to in terms of academic and community so I think first off, we've just been pleased to see broad adoption across all specialties as well as settings on academic and community, hematology oncology, as well as an increasing number of allergists.

是的，當然。因此，正如凱特所提到的，我認為處方的廣度確實是像這樣的慢性罕見疾病推出中最重要的先導指標之一。我們認為這是持續增長和處方的一個很好的領導。您在學術和社區方面談到的趨勢，所以我認為首先，我們很高興看到所有專業以及學術和社區、血液腫瘤學以及越來越多的領域的廣泛採用過敏症專科醫生的數量。

The trend that we're seeing this quarter, I think probably speaks more to the extent of deepening that we're seeing which is likely occurring more within those centers of excellence. But as I alluded to before, we're really seeing deepening along that entire curve of providers who have adopted AYVAKIT. And so we expect both continued breadth as well as continued depth across all specialties and settings over time.

我認為我們本季看到的趨勢可能更多地說明了我們所看到的深化程度，這可能更多地發生在這些卓越中心內。但正如我之前提到的，我們確實看到採用 AYVAKIT 的供應商在整個曲線上不斷深化。因此，我們期望隨著時間的推移，所有專業和環境的廣度和深度都會持續成長。

Peter Lawson, Barclays.

彼得·勞森，巴克萊銀行。

Hey, good morning. This is Alex on for Peter at Barclays. Thank you for taking our question. Just on elenestinib, just wondering if you could remind us how that molecule differentiates or improves and the profile of AYVAKIT. And then how should we think about the time needed to complete the pivotal study? Thank you.

嘿，早安。我是巴克萊銀行的亞歷克斯 (Alex) 替補彼得 (Peter)。感謝您提出我們的問題。就 elenestinib 而言，只是想知道您能否提醒我們該分子如何區分或改善以及 AYVAKIT 的概況。那我們應該如何考慮完成關鍵研究所需的時間呢？謝謝。

Thanks for the question. Christy, do you want to talk about elenestinib?

謝謝你的提問。克里斯蒂，你想談談埃萊替尼嗎？

Sure. So we're moving out on elenestinib forward. It's our next-generation KIT D816 inhibitor. As we said before, it's another very potent selective molecule. Primary point of differentiation is around brain penetrants although increasingly we know we don't think that's necessarily relevant in ISM. So our strategy is really to bring this forward in a way where we can really clinically differentiate and address where the disease is going in ISM.

當然。因此，我們將繼續使用 elenestinib。它是我們的下一代 KIT D816 抑制劑。正如我們之前所說，它是另一種非常有效的選擇性分子。主要的區別點是大腦滲透劑，儘管我們越來越知道我們認為這與 ISM 不一定相關。因此，我們的策略實際上是以一種我們能夠真正在臨床上區分和解決 ISM 中疾病發展方向的方式來推進這一進程。

So we now understand the biology of the disease, the spectrum of the disease in a much deeper way than we did 10 years ago at Blueprint Medicines. And I think the frontier has really moved in terms of what the expectations are for treating patients and really moving towards that goal of really eradicating what is a very serious chronic disease in that patient setting.

因此，我們現在比 10 年前在 Blueprint Medicines 更深入地了解了這種疾病的生物學和疾病譜。我認為，在治療患者的期望方面，前沿確實發生了變化，並且真正朝著真正根除患者環境中非常嚴重的慢性疾病的目標邁進。

And so when we think about Part two of HARBOR we're really being thoughtful in terms of how we bring elenestinib forward to really demonstrate that differentiated clinical impact on ISM. And again, we'll be sharing more about that as we head into the end of the year.

因此，當我們考慮 HARBOR 的第二部分時，我們確實在考慮如何將 elenestinib 向前推進，以真正證明對 ISM 的差異化臨床影響。再次，當我們進入年底時，我們將分享更多相關資訊。

Andrew Berens, Leerink.

安德魯貝倫斯，萊林克。

Thanks and congrats on the numbers. Two questions from me. I was wondering if you could give us some insight into the 20% free drug number. I recall in Q1 of last year, you told us a bit over $5 million of the ISM revenues, orphan free drug purchase by charitable organizations. Can you give us some number this quarter?

感謝並祝賀這些數字。我有兩個問題。我想知道您能否給我們一些關於 20% 免費藥品數量的見解。我記得去年第一季度，您告訴我們 ISM 收入中超過 500 萬美元是由慈善組織購買孤兒免費藥品。您能給我們一些本季的數字嗎？

Do these patients have their drug purchased by charitable organizations? Are they ultimately converted to paying patients? Just trying to get a sense, whether they're expected to grow as the patient numbers increase in order to maintain this sub 20%. And then the second question would be on what percentage of the ISM patients escalate to 50 milligrams or higher? Thanks.

這些患者的藥物是由慈善組織購買的嗎？他們最終會轉變為付費病患嗎？只是想了解一下，他們是否會隨著患者數量的增加而增長，以維持在 20% 以下的水平。那麼第二個問題是 ISM 患者中有多少比例升級到 50 毫克或更高？謝謝。

Thanks for the question Andy. Christy, do you want to take both of those?

謝謝安迪的提問。克里斯蒂，你想把這兩個都拿走嗎？

Sutre. Nice to hear from you, Andy. We are, as you said, really happy to see kind of the dynamics that we're seeing with free jog in this in this launch. And a lot of the evolution comes from the underlying dynamics in the patient population, right.

蘇特。很高興收到你的來信，安迪。正如您所說，我們非常高興看到我們在這次發布中看到的自由慢跑的動態。很多演變來自於患者群體的潛在動態，對吧。

So as Kate said, we are launching really more into our chronic immunology space with ISM. Patients are younger. The payer mix is different so we see more commercial commercial patients. And that naturally will help start to reduce our exposure to free drug.

正如 Kate 所說，我們正在透過 ISM 向慢性免疫學領域進行更多工作。患者年齡較輕。付款人組合不同，因此我們看到更多商業患者。這自然有助於開始減少我們接觸免費毒品的機會。

In addition, we see some benefit this year from the IRA redesign, which has limited patient out of pocket and basically means that more patients can afford to access pain therapy, whether that's on their own or with the addition of external sources of support that patients may find on their own. The dynamic is very different than what we saw last year that you're alluding to.

此外，我們看到今年IRA 的重新設計帶來了一些好處，它限制了患者自掏腰包，基本上意味著更多的患者有能力接受疼痛治療，無論是單獨治療還是在患者獲得外部支持的情況下進行治療。這種動態與我們去年看到的你提到的情況非常不同。

The reason why we quantified and were able to quantify that dynamic last year was because it was in the setting of advanced SM and we knew that that that sort of tailwind was temporary and would unwind right?

去年我們量化並能夠量化這種動態的原因是因為它是在先進 SM 的背景下，我們知道這種順風是暫時的並且會減弱，對嗎？

So we knew that we had a proportion of patients who would access free drug, but unfortunately or paid therapy, but that would have to move back to free drug.

所以我們知道我們有一部分患者可以獲得免費藥物，但不幸的是或付費治療，但這必須回到免費藥物。

In this case, what we're seeing is that patients who access commercial therapy, we expect that to be a permanent situation for as long as they're clinically indicated to be on treatment, which again, an ISM tend to be for long periods of time. So we expect that that benefit to continue.

在這種情況下，我們看到的是，接受商業治療的患者，只要臨床表明需要接受治療，我們預計這種情況就會成為永久性的情況，同樣，ISM 往往會持續很長時間的時間。因此，我們預計這種好處將持續下去。

As Philina said, we think that the rate of free drug overall has reached a relatively steady state. So as we think about guidance going forward, we wouldn't expect that to be a big driver one way or the other.

正如菲利納所說，我們認為整體免費毒品率已經達到了一個相對穩定的狀態。因此，當我們考慮未來的指導時，我們並不認為這會成為一個重要的推動因素。

You want talk a little bit about what we're seeing in terms of the 50 milligram usage?

您想談談我們在 50 毫克劑量方面所看到的情況嗎？

Yeah. So we continue to report our patients starting at 25 milligrams being the vast majority of patients are seeing across SM. We really don't see a lot of utilization of 50 milligram. Where we've seen it tends to primarily be utilized in centers of excellence where they're really treating the full spectrum of SM patients.

是的。因此，我們繼續報告我們的患者從 25 毫克開始，絕大多數患者都在接受 SM。我們確實沒有看到 50 毫克的大量使用。我們看到它主要用於卓越中心，在那裡他們真正治療所有 SM 患者。

And we know it's the spectrum right? We see patients from advance to indolent. It's a very clinically heterogeneous patient population and that each patient need is unique. And so the fact that we have a range of safe and effective doses available for patients that prescribers can easily access is a huge strength of this profile.

我們知道這是頻譜，對嗎？我們看到病人從晚期到惰性。這是一個臨床上非常多樣化的患者群體，每個患者的需求都是獨特的。因此，我們為患者提供了一系列安全有效的劑量，處方者可以輕鬆獲得，這是這一概況的巨大優勢。

One of the things you've learned about SM is that it's not a one-size-fits-all disease. It's not a one dose fits all patients' disease. But for the as majority of ISM patients, 25 milligrams is the right dose and that's certainly what we are continuing to see in the real world.

關於 SM，您了解到的一件事是，它不是一種一刀切的疾病。它不是一種適合所有患者疾病的劑量。但對於大多數 ISM 患者來說，25 毫克是正確的劑量，這肯定是我們在現實世界中繼續看到的情況。

Sudan Loganathan, Stephens.

蘇丹·洛加納森，史蒂芬斯。

Hi, everyone. Good morning and congratulations again on your great quarter. My first question is more big picture on your views on business development. With the growing cash position and ongoing acceleration of AYVAKIT launch, do you have the appetite for bolt-on deals to bring in earlier late-stage clinical assets into the mix that may benefit from the groundwork that vacant AYVAKIT has set?

大家好。早上好，再次恭喜您度過了美好的季度。我的第一個問題是關於您對業務發展的看法。隨著現金狀況的不斷增長和 AYVAKIT 推出的持續加速，您是否有興趣進行補充交易，將早期的後期臨床資產納入組合中，從而受益於空缺的 AYVAKIT 奠定的基礎？

Or is the focus still on developing the pipeline from discovery stage kind of endeavors akin to what you're doing with the targeted protein degradation portfolio?

或者，重點仍然是開發從發現階段開始的管道，類似於您對目標蛋白質降解產品組合所做的工作？

And then secondly, on HARBOUR study, do you anticipate there would be any challenges with enrolling for ISM patients for the study with the effective AYVAKIT on the market for the same indication? Will there be any patients enrolled in this program that may actually be refractory to AYVAKIT, getting on with that profile fit test out there?

其次，關於 HARBOR 研究，您預計招募 ISM 患者參加市場上針對相同適應症的有效 AYVAKIT 的研究是否會遇到任何挑戰？是否會有任何參加該計劃的患者實際上可能對 AYVAKIT 耐藥，並繼續進行個人資料適合性測試？

Thank you, Sudan for the questions and welcome. We really appreciate your kind of joining the Blueprint coverage team here. So in terms of those questions maybe Christy, you can start with BD and then Fouad, you want to talk about HARBOR.

謝謝蘇丹提出的問題並表示歡迎。我們非常感謝您加入 Blueprint 覆蓋團隊。因此，就這些問題而言，克里斯蒂，您可以從 BD 開始，然後是福阿德，您想談談 HARBOR。

But -- and Sudan one of the things that I think has been a strength of Blueprint Medicines in the almost nine years that I've been here is that we consistently think about business development, both on the buy-side and sell-side as ways of achieving and optimizing our corporate goals and optimizing our business, but maybe Christy, do you want to talk a bit more specifically on how we're thinking about BD?

但是，我認為蘇丹在我任職的近九年裡一直是 Blueprint Medicines 的優勢之一，那就是我們始終如一地考慮業務發展，無論是在買方還是賣方方面實現和優化我們的企業目標以及優化我們的業務的方法，但也許克里斯蒂，您想更具體地談談我們如何看待BD 嗎？

Yeah. So as Kate said, I mean, this is to us a strategic lever to optimize the portfolio in terms of both inbound and outbound business development. We are constantly sort of engaged on that front scanning kind of the external environment, looking for things that could be a fit, talking to strategic companies again both from an inbound and outbound business development perspective.

是的。正如凱特所說，我的意思是，這對我們來說是一個策略槓桿，可以在入境和出境業務發展方面優化投資組合。我們不斷地對外部環境進行正面掃描，尋找合適的東西，從入境和出境業務發展的角度再次與策略公司交談。

We are very clear about what our priorities are, right? So we've been very clear in terms of capital allocation, our time and attention and effort. It's very much from a clinical and commercial perspective particularly focused on advancing our muscle disorder franchise. And that's really around continuing to execute the AYVAKIT launch as well as the AYVAKIT clinical development program which continues to be prolific and generate a lot of important data and bringing elenestinib forward.

我們非常清楚我們的優先事項是什麼，對嗎？所以我們在資本配置、時間、注意力和努力方面都非常清楚。這在很大程度上是從臨床和商業角度出發，特別注重推進我們的肌肉疾病專營權。這實際上是圍繞繼續執行 AYVAKIT 上市以及 AYVAKIT 臨床開發計劃而言的，該計劃不斷豐富並產生大量重要數據並推動 elenestinib 向前發展。

And then, very importantly, BLU-808, which as we said on the call, we are really moving towards we think an inflection point here as we get that Phase 1 data and believe that we could advance across a number of fronts to bring this forward to patients suffering from mast cell disorders.

然後，非常重要的是，BLU-808，正如我們在電話中所說，我們確實正在邁向拐點，因為我們獲得了第一階段的數據，並相信我們可以在多個方面取得進展，以實現這一目標轉發給患有肥大細胞疾病的患者。

So it is our focus and nothing from a BD perspective is distracting from that focus. But of course, we're going to continue to look and are open to things that makes sense strategically both from an inbound and outbound perspective.

所以這是我們的重點，從 BD 的角度來看，沒有任何事情可以分散我們的注意力。但當然，我們將繼續尋找並願意接受從入站和出站角度來看具有戰略意義的事情。

And maybe to just add one other thing is that we have been -- we would be remiss not to talk about the fact that our discovery team has been prolific in driving innovation at Blueprint Medicines. I think we're now at 17 development candidates that come out of our labs.

也許要補充的另一件事是，如果我們不談論這樣一個事實，即我們的發現團隊在推動 Blueprint Medicines 的創新方面取得了豐碩成果，那就太失職了。我想我們現在有 17 位來自我們實驗室的開發候選人。

Like we're the only company that brought two candidates from our lab, two FDA approval in less than 10 years, our research and development teams are just absolutely top notch, top quality and that just gives us an incredible opportunity to have that internal innovation engine that really enables us to keep a high bar as we think about external innovation.

就像我們是唯一一家在不到10 年的時間裡從我們的實驗室帶來兩名候選人、兩名FDA 批准的公司一樣，我們的研發團隊絕對是一流的、一流的質量，這給我們提供了一個難以置信的機會來進行內部創新真正使我們在考慮外部創新時保持高標準的引擎。

Fouad, do you want to talk about HARBOR?

Fouad，你想談談 HARBOR 嗎？

I mean, I'm going to build on the innovation team. And I'm very happy to really say that our teams continue to innovate to really design a registrational strategy for HARBOR that will differentiate elenestinib from AYVAKIT. In answer to Christy's earlier point major questions that will be -- we are needed to be answered in many years from now.

我的意思是，我將加強創新團隊的建立。我很高興地說，我們的團隊不斷創新，真正為 HARBOR 設計了註冊策略，這將使 elenestinib 與 AYVAKIT 區分開來。為了回答克里斯蒂之前提出的主要問題，我們需要在多年後得到答案。

In terms of execution of elenestinib and the availability of AYVA as the standard of care today, we didn't expect major challenges in terms of recruiting patients. First because institution that do clinical trial that really have that skill set and that performance aspect, but at the same time doing clinical trial, but also treating patients and they know how to do this.

就 elenestinib 的執行以及 AYVA 作為當今護理標準的可用性而言，我們預計在招募患者方面不會遇到重大挑戰。首先，因為進行臨床試驗的機構確實擁有相應的技能和績效方面，但在進行臨床試驗的同時，也要治療患者，他們知道如何做到這一點。

Also, I mean, the study will open in the US. And as we did with Pioneer the study will also open in a number of international sites to support the recruitment and to also have patients from other countries to get access to elenestinib trial. So we are very confident about our ability to execute elenestinib HARBOR Part 2 study.

另外，我的意思是，這項研究將在美國展開。正如我們與 Pioneer 所做的那樣，該研究也將在許多國際站點開放，以支持招募，並讓來自其他國家的患者參與 elenestinib 試驗。因此，我們對執行 elenestinib HARBOR 第 2 部分研究的能力非常有信心。

We currently have no further questions. So I would like to turn the call back to the CEO, Kate Haviland, for closing remarks. Please go ahead.

目前我們沒有進一步的問題。因此，我想將電話轉回給執行長凱特哈維蘭 (Kate Haviland)，讓其致閉幕詞。請繼續。

Thank you, operator. And as we cross into the second half of 2022, we are in a tremendously strong position. Thanks to our people who are driving the success of Blueprint Medicines.

謝謝你，接線生。當我們進入 2022 年下半年時，我們處於非常有利的地位。感謝推動 Blueprint Medicines 成功的我們的員工。

I'm extremely proud of the hard work, contributions and dedication of our entire team at Blueprint Medicines as we deliver on our commitment to patients with systemic mastocytosis and beyond.

我對 Blueprint Medicines 整個團隊的辛勤工作、貢獻和奉獻感到非常自豪，因為我們兌現了對系統性肥大細胞增多症及其他患者的承諾。

Thank you all for taking the time to join us today. And we'll thank you for your continued support of Blueprint Medicines.

感謝大家今天抽空加入我們。我們將感謝您對 Blueprint Medicines 的持續支持。

Ladies and gentlemen, this concludes today's call. Thank you for joining. You may now disconnect your lines.

女士們、先生們，今天的電話會議到此結束。感謝您的加入。現在您可以斷開線路。