Blueprint Medicines Corp (BPMC) 2024 Q3 法說會逐字稿

Good morning. My name is Nadia, and I'll be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicines third-quarter 2024 financial results conference call. (Operator Instructions)

早安.我叫納迪亞，今天我將擔任你們的會議接線生。此時此刻，我歡迎大家參加 Blueprint Medicines 2024 年第三季財務業績電話會議。（操作員說明）

Jenna Cohen, you may begin your conference.

珍娜·科恩，您可以開始會議了。

Thank you, Nadia. Good morning, everyone, and welcome to Blueprint Medicines third-quarter 2024 financial and operating results conference call.

謝謝你，納迪亞。大家早安，歡迎參加 Blueprint Medicines 2024 年第三季財務與營運業績電話會議。

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 today, 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。您可以造訪我們網站 www.blueprintmedicines.com 的投資者部分，造訪新聞稿以及我們今天將要審查的幻燈片。

Joining me today are Kate Haviland, Chief Executive Officer; Philina Lee, Chief Commercial Officer, Christy Rossi; Chief Operating Officer; and Mike 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，克里斯蒂·羅西首席商務官；首席營運長；和財務長 Mike Landsittel。研發總裁 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屬於前瞻性陳述，如幻燈片 3 中所述，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 morning, we reported another strong quarter of AYVAKIT revenue growth, adding additional momentum to our impressive year-to-date results and providing a strong foundation for us to drive long-term shareholder value creation in 2025 and beyond.

謝謝你，珍娜，大家早安。今天早上，我們報告了 AYVAKIT 收入又一個強勁的季度增長，為我們迄今為止令人印象深刻的業績增添了額外動力，並為我們在 2025 年及以後推動長期股東價值創造奠定了堅實的基礎。

AYVAKIT's sales trajectory has given us the confidence to raise our revenue expectations significantly over the course of this year. And we now estimate that we will end the year between $475 million and $480 million in product revenue. We are on a $0.5 billion dollar run rate in our first full year of ISM launch, placing AYVAKIT firmly on the path to realizing its more than $2 billion peak revenue opportunity and positioning AYVAKIT's launch in ISM to be among the most successful rare disease launches to date.

AYVAKIT 的銷售軌跡讓我們有信心大幅提高今年的營收預期。我們現在估計年底產品收入將在 4.75 億至 4.8 億美元之間。在ISM 推出的第一個全年，我們的運行率為5 億美元，這使AYVAKIT 堅定地走上實現其超過20 億美元峰值收入機會的道路，並使AYVAKIT 在ISM 中的推出成為最成功的罕見疾病推出之一。

To build a blockbuster medicine, we must demonstrate a significantly meaningful and differentiated clinical impact that transforms treatment paradigms in diseases with high medical need. This is so simple to say and not easy to do. At Blueprint, we have demonstrated that AYVAKIT drives clinically meaningful, deep, and sustained symptom impact for patients with ISM, now over several years in the PIONEER study, with a consistent and well-tolerated safety profile.

為了打造一款重磅藥物，我們必須證明其具有顯著意義和差異化的臨床影響，能夠改變醫療需求高的疾病的治療模式。這說起來簡單，做起來卻不容易。在 Blueprint，我們已經證明 AYVAKIT 對 ISM 患者俱有臨床意義、深度和持續的症狀影響，目前已經在 PIONEER 研究中進行了數年，並且具有一致且耐受性良好的安全性。

Treatment with AYVAKIT is allowing ISM patients to reclaim control of their lives and is transforming the treatment paradigm in ISM. With continued long-term data generation and strong commercial adoption, we believe AYVAKIT is setting up to be the durable market leader across the spectrum of both advanced and indolent SM for years to come.

AYVAKIT 治療使 ISM 患者重新掌控自己的生活，並正在改變 ISM 的治療模式。憑藉持續的長期數據生成和強大的商業應用，我們相信 AYVAKIT 在未來幾年將成為先進 SM 和惰性 SM 領域持久的市場領導者。

Building a blockbuster brand has never been easy. And it has only become harder as therapeutic areas have become saturated, as legislative, regulatory, and market access headwinds have strengthened, all on the backdrop of what has been a challenging macro environment in recent years.

建立一個轟動的品牌從來都不是一件容易的事。隨著治療領域的飽和，立法、監管和市場准入的阻力加大，這一切都在近年來充滿挑戰的宏觀環境的背景下變得更加困難。

At Blueprint, we have successfully managed through all of these challenges. Our commercial and medical teams have done a tremendous job navigating the range of short-term quarterly dynamics we face, including the industry-wide dynamics all medicines face, the dynamics that are intrinsic to rare disease markets and launches, as well as the dynamics that are unique and specific to the SM market.

在 Blueprint，我們成功處理了所有這些挑戰。我們的商業和醫療團隊在應對我們面臨的一系列短期季度動態方面做了巨大的工作，包括所有藥物面臨的全行業動態、罕見疾病市場和上市所固有的動態，以及是SM 市場獨有且特定的。

While managing all these short-term dynamics, we have always maintained conviction in AYVAKIT's more than $2 billion peak revenue opportunity. And we continue to be focused on building a foundation for long-term growth and delivering compelling results year over year. Philina will talk in more detail about our commercial results shortly.

在管理所有這些短期動態的同時，我們始終堅信 AYVAKIT 擁有超過 20 億美元的最高收入機會。我們將繼續致力於為長期成長奠定基礎，並逐年提供引人注目的成果。Philina 很快就會更詳細地討論我們的商業成果。

Leveraging our leadership in SM and our deep expertise in mast cell biology, we are working to broaden our impact by addressing the significant medical needs of thousands of patients with BLU-808, our wild-type KIT inhibitor. We designed BLU-808 to raise the bar on what a treatment for chronic urticaria and other mast cell-mediated inflammatory diseases can offer by taking into account the full patient experience, efficacy, tolerability, and the burden associated with administration.

憑藉我們在SM 領域的領導地位和在肥大細胞生物學方面的深厚專業知識，我們正在努力透過使用我們的野生型KIT 抑制劑BLU-808 來滿足數千名患者的重大醫療需求，從而擴大我們的影響力。我們設計 BLU-808 的目的是透過考慮完整的患者體驗、療效、耐受性以及與給藥相關的負擔，提高慢性蕁麻疹和其他肥大細胞介導的發炎性疾病的治療標準。

We see the opportunity for BLU-808 as twofold: to command a large share of significant established markets and to drive further growth by expanding the treated populations in those markets. Christy will provide an update on the progress we have made across our portfolio later on the call.

我們認為 BLU-808 有雙重機會：在重要的成熟市場中佔據很大份額，並透過擴大這些市場的治療人群來推動進一步成長。克里斯蒂將在稍後的電話會議上介紹我們在投資組合方面取得的最新進展。

As we report our Q3 results today, AYVAKIT's strong revenue ramp, coupled with our disciplined investment and our most compelling product opportunities, places us in a position to realize a significant decline in cash burn this year while maintaining our focus on long-term growth and value creation. We are building a solid financial foundation for Blueprint's future. Mike will talk more about our financial results later on the call, and we look forward to reviewing our portfolio priorities in early 2025.

當我們今天報告第三季業績時，AYVAKIT 強勁的收入成長，加上我們嚴格的投資和最引人注目的產品機會，使我們能夠在今年實現現金消耗的大幅下降，同時保持對長期增長的關注和價值創造。我們正在為 Blueprint 的未來奠定堅實的財務基礎。麥克稍後將在電話會議上詳細討論我們的財務業績，我們期待在 2025 年初審查我們的投資組合優先事項。

I will now turn it over to Philina to discuss this quarter's commercial performance in more detail.

我現在將把它交給 Philina，更詳細地討論本季的商業表現。

Thanks, Kate.

謝謝，凱特。

In the third quarter, AYVAKIT achieved $128.2 million in net product revenue, with $113.1 million in the US and $15.1 million ex-US. This represents a 137% increase year over year, and our conviction in this blockbuster brand has never been stronger. Our team's efforts are coming to fruition as we build this market, and AYVAKIT's strong launch trajectory proves our success.

第三季度，AYVAKIT 實現產品淨收入 1.282 億美元，其中美國市場收入 1.131 億美元，美國以外市場收入 1,510 萬美元。這意味著同比增長 137%，我們對這個熱門品牌的信念從未如此堅定。隨著我們建立這個市場，我們團隊的努力正在取得成果，AYVAKIT 強勁的上市軌跡證明了我們的成功。

Growth this quarter was driven by strengths in our key business fundamentals. First, we continue to see strong and steady growth in patients on AYVAKIT, driven by new patient starts and low discontinuations. Growth in patients on therapy is driving AYVAKIT's successful launch. At our last call, we anticipated seasonal dynamics around summer holidays might impact patient starts and compliance, but this turned out to be less of an issue than expected.

本季的成長是由我們關鍵業務基本面的優勢所推動的。首先，在新患者入院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。接受治療的患者數量的增長推動了 AYVAKIT 的成功上市。在我們上次的電話會議中，我們預計暑假前後的季節性動態可能會影響患者的開始和依從性，但事實證明這並不像預期的那樣是一個問題。

Our team did a great job managing through these dynamics, resulting in strong demand towards the end of Q3. We have a large base of patients on therapy, and we expect this to continue growing. Compliance remained high, consistent with what we've seen, and trends in duration therapy remained strong, demonstrating the real-world benefit patients see on AYVAKIT.

我們的團隊在應對這些動態方面做得非常出色，導致第三季末出現了強勁的需求。我們有大量接受治療的患者，我們預計這一數字將繼續增長。依從性仍然很高，與我們所看到的一致，而且治療持續時間的趨勢仍然強勁，證明了患者在 AYVAKIT 上看到的現實益處。

Second, our mix of free and commercial goods remains stable. Our average free goods rate since ISM approval is in the mid-teens and has stabilized over the past two quarters. We expect this to remain consistent for the remainder of the year.

其次，我們的免費和商業產品組合保持穩定。自 ISM 批准以來，我們的平均免費商品率處於十幾歲左右，並且在過去兩個季度中已趨於穩定。我們預計這一情況在今年剩餘時間內將保持一致。

Finally, our international team delivered strong results this quarter, driving growth in advanced SM across several geographies and in ISM with the launch underway in Germany. Germany comprises the majority of international sales, and the ISM launch dynamics we're seeing there mirror what we've seen in the US. In the third quarter, strong growth and volume offset a lower price accrual from our planned German price reassessment process, which will be complete by early next year. We anticipate geographic expansion across both advanced SM and ISM to continue to drive growth in 2025 and beyond as we launch ISM in additional markets.

最後，我們的國際團隊在本季度取得了強勁的業績，推動了多個地區的先進 SM 以及 ISM 的成長（在德國推出）。德國佔國際銷售的大部分，我們在那裡看到的 ISM 發布動態與我們在美國看到的情況相似。第三季度，強勁的成長和銷售抵消了我們計劃的德國價格重新評估過程帶來的較低的應計價格，該過程將於明年初完成。我們預計，隨著我們在其他市場推出 ISM，先進 SM 和 ISM 的地理擴張將繼續推動 2025 年及以後的成長。

Breadth and depth of prescribing are strong lead indicators of continued growth. This chart shows how first positive experience with AYVAKIT leads to repeat prescribing among the top 400 providers by SM patient volume. But this is just part of the story. We're engaging with several thousand providers beyond the top 400, and adoption is growing across this broader range.

處方的廣度和深度是持續成長的有力先行指標。這張圖表顯示了 AYVAKIT 的首次積極體驗如何導致 SM 患者數量排名前 400 名的醫療服務提供者重複處方。但這只是故事的一部分。我們正在與 400 強之外的數千家提供者合作，並且在更廣泛的範圍內採用率正在不斷增長。

As AYVAKIT experience grows, we see new hemoncs and allergists prescribing, with adoption evenly split across academic and community settings. These dynamics are exactly what you'd want to see in a strong launch, and they plant the seeds for continued growth.

隨著 AYVAKIT 經驗的增長，我們看到新的血紅素和過敏專家開出處方，學術和社區環境中的採用率均勻。這些動態正是您希望在強勁的發布中看到的，它們為持續成長播下了種子。

We've also seen the first examples of prescribing by additional specialties, such as dermatologists. For example, we're seeing cases where dermatologists can become the local SM champion, motivated to diagnose and move more patients to treatment. This dynamic bodes well, proving yet another opportunity to further grow the market and our ability to capture it with AYVAKIT. Awareness of SM continues to grow across a broadening spectrum of specialists who touch the constellation of disease symptoms.

我們也看到了由皮膚科醫生等其他專業人士開處方的第一個例子。例如，我們看到皮膚科醫生可以成為當地 SM 冠軍，積極診斷並讓更多患者接受治療。這種動態是個好兆頭，證明了進一步發展市場的另一個機會，以及我們透過 AYVAKIT 抓住這個市場的能力。越來越多接觸疾病症狀的專家對 SM 的認識不斷提高。

We understand the SM market better than anyone else. What activates patients to start a therapy that targets the root cause of ISM? What drives urgency to treat among providers? And how to streamline access to therapy?

我們比任何人都更了解SM市場。是什麼促使患者開始針對 ISM 根本原因的治療？是什麼促使醫療服務提供者迫切需要治療？以及如何簡化治療的取得？

Now, let's dive into some of our latest provider and patient initiatives. Our team recently launched a new branded campaign for providers, designed to challenge the notion of well controlled, along with resources that highlight the two-year safety and efficacy data we presented at the European Academy of Allergy and Clinical Immunology Conference. These data are valuable to providers considering AYVAKIT, and Christy will share more on this.

現在，讓我們深入了解一些最新的提供者和患者計劃。我們的團隊最近為提供者發起了一項新的品牌活動，旨在挑戰良好控制的概念，並提供強調我們在歐洲過敏和臨床免疫學會議上提出的兩年安全性和有效性數據的資源。這些數據對於考慮 AYVAKIT 的提供者來說非常有價值，Christy 將分享更多相關內容。

Having made progress educating the provider base and growing AYVAKIT experience among hemoncs and allergists, we can now further expand on our direct-to-patient initiatives. We recently launched a patient campaign to raise awareness and spotlight how AYVAKIT targets the source of the disease. We also launched a new patient mentor program, increased support for face-to-face patient events, and expanded our patient ambassador programs. We know that patients find it helpful to hear from other patients as they consider starting AYVAKIT, and an educated patient is a catalyst for treatment.

在教育提供者群體方面取得了進展，並在血紅素和過敏症專家中不斷積累 AYVAKIT 經驗後，我們現在可以進一步擴展我們的直接面向患者的計劃。我們最近發起了一項患者運動，以提高人們的認識並關注 AYVAKIT 如何針對疾病來源。我們還推出了新的患者導師計劃，增加了對面對面患者活動的支持，並擴大了我們的患者大使計劃。我們知道，患者在考慮開始 AYVAKIT 時發現聽取其他患者的意見很有幫助，而受過教育的患者是治療的催化劑。

Our efforts with the SM community are working. AYVAKIT is helping more patients every quarter, and we are continually enhancing and expanding our initiatives as we drive this launch towards its peak potential.

我們與 SM 社群的努力正在發揮作用。AYVAKIT 每個季度都在幫助更多患者，我們將不斷加強和擴大我們的舉措，推動此次發布發揮其最大潛力。

I'll now turn it over to Christy to share more about our data generation efforts and near-term catalysts as we head into 2025.

現在，我將把它交給 Christy，讓她分享更多關於我們在邁入 2025 年時的數據生成工作和近期催化劑的信息。

Thanks, Philina.

謝謝，菲莉娜。

We've been treating SM patients with AYVAKIT in clinical trials since 2016 and have spent the last eight-plus years amassing a significant body of evidence on its long-term impact across the spectrum of this disease. In advanced SM, we've been able to demonstrate significantly improved overall survival versus prior standard-of-care therapies. And in ISM, we know that HCPs and patients find longer-term data on the safety and clinical impact of AYVAKIT meaningful and motivating in the setting of a chronic, lifelong disease.

自 2016 年以來，我們一直在臨床試驗中使用 AYVAKIT 治療 SM 患者，並在過去八年多的時間裡積累了大量證據，證明其對該疾病的長期影響。在高級 SM 中，我們已經能夠證明與先前的標準護理療法相比，整體存活率顯著提高。在 ISM 中，我們知道 HCP 和患者發現有關 AYVAKIT 的安全性和臨床影響的長期數據對於慢性終身疾病而言具有意義和激勵作用。

We've continued to publish long-term follow-up data from the open-label extension of the PIONEER study. Most recently, we presented updated data demonstrating that with median follow-up of more than two years, and with some patients treated as long as four years, AYVAKIT showed durable efficacy and a favorable safety profile. Safety data were consistent for a subset of patients who dose escalated to 50 milligrams once daily, reinforcing the flexibility that HCPs have to customize treatment based on the individual needs of their patients.

我們持續發布 PIONEER 研究開放標籤擴展的長期追蹤資料。最近，我們提供的更新數據表明，中位追蹤時間超過兩年，並且某些患者的治療時間長達四年，AYVAKIT 顯示出持久的療效和良好的安全性。部分患者的安全性數據是一致的，這些患者的劑量增加到每天一次 50 毫克，這增強了醫療保健專業人員根據患者的個人需求量身定制治療的靈活性。

What sets Blueprint apart, however, is not just the mountain of evidence we continue to amass with AYVAKIT. Our team has developed a tremendous command of the SM market by being at the table with a broad group of healthcare providers diagnosing and treating patients every day. We have an unparalleled depth of knowledge and expertise across the continuum, from research, through development, to commercialization, which affords us an evolved understanding of patient and provider needs over the long term. This creates a virtuous cycle where insight fuels innovation, enabling us to drive progress with AYVAKIT and guiding us on how to deliver an evolved value proposition with elenestinib, our next-generation KIT D816V inhibitor.

然而，Blueprint 的與眾不同之處不僅僅是我們透過 AYVAKIT 不斷累積的大量證據。我們的團隊每天與眾多醫療保健提供者一起診斷和治療患者，從而在 SM 市場上佔據了巨大的主導地位。我們在從研究、開發到商業化的整個過程中擁有無與倫比的知識和專業知識深度，這使我們能夠不斷深入地了解患者和醫療服務提供者的長期需求。這創造了一個良性循環，洞察力推動創新，使我們能夠推動 AYVAKIT 的進步，並指導我們如何透過我們的下一代 KIT D816V 抑制劑 elenestinib 提供不斷發展的價值主張。

And we're establishing this same virtuous cycle in mast cell disorders more broadly. It was insight and feedback from allergists that inspired us to pursue a potent, selective, and tunable oral wild-type KIT inhibitor, resulting in BLU-808. And just last weekend at the American College of Allergy, Asthma and Immunology Meeting in Boston, I saw firsthand evidence of scientific exchange, sparking new ideas and driving strategy and impact across our mast cell portfolio.

我們正在更廣泛地在肥大細胞疾病中建立同樣的良性循環。過敏症專家的見解和回饋激勵我們追求一種有效的、選擇性的、可調節的口服野生型 KIT 抑制劑，最終誕生了 BLU-808。就在上週末，在波士頓舉行的美國過敏、氣喘和免疫學院會議上，我看到了科學交流的第一手證據，激發了新的想法，推動了我們肥大細胞組合的策略和影響。

As we approach the end of what has truly been an exceptional year and look ahead to 2025, I'd like to touch on some of the near-term milestones and catalysts our team is focused on, starting with our primary strategic priority of advancing this mast cell portfolio. This includes the successful global commercial launch of AYVAKIT, which Philina discussed today.

隨著我們真正不平凡的一年即將結束並展望 2025 年，我想談談我們團隊關注的一些近期里程碑和催化劑，首先是我們推進這一目標的首要戰略重點肥大細胞組合。這包括 Philina 今天討論的 AYVAKIT 的成功全球商業發布。

It also includes the advancement of elenestinib, where we remain on track to initiate the registration-enabling Part 2 of the HARBOR study by year-end, and BLU-808, which has been moving through a Phase 1 study in healthy volunteers. We anticipate sharing this data early next year, including initial data on BLU-808's safety profile, drug-like properties, and early biomarker responses that will help to inform how we think about the potential for broad disease impact. I hope you have a chance to dial in for the second in our series of science-focused seminars on November 14, where we plan to talk more about the strategic development plans for our mast cell therapy franchise.

它還包括 elenestinib 的進展，我們仍有望在年底前啟動 HARBOR 研究的註冊第 2 部分，以及 BLU-808，該藥物一直在健康志願者中進行第一階段研究。我們預計明年初分享這些數據，包括 BLU-808 安全性、類藥特性和早期生物標記反應的初步數據，這將有助於我們如何看待廣泛疾病影響的潛力。我希望您有機會參加 11 月 14 日舉辦的以科學為主題的系列研討會的第二場，我們計劃在會上更多地討論我們肥大細胞療法特許經營權的戰略發展計劃。

Regarding our cell cycle portfolio, we have been closely tracking the emerging data sets, including those shared at ESMO, that continue to validate the promise of targeting CDK2. We are nearing the end of the combination dose escalation portion of the Phase 1 VELA study, and in parallel, we have also advanced our next-generation programs, particularly our CDK2 degrader, more quickly than we originally expected.

關於我們的細胞週期組合，我們一直在密切追蹤新興資料集，包括在 ESMO 共享的資料集，這些資料集繼續驗證針對 CDK2 的承諾。我們的 VELA 一期研究的聯合劑量遞增部分已接近尾聲，與此同時，我們也比我們最初預期的更快地推進了下一代項目，特別是我們的 CDK2 降解劑。

Given the significant investment and capabilities required to move into later stage breast cancer trials, we've been clear that we will not move BLU-222 forward beyond this phase of development on our own and have been engaging in strategic partnership discussions. Through these conversations, we are evaluating the emerging data from CDK2 inhibitors, as well as the profiles of our next-generation assets, to determine what may be the best-in-class approach and, therefore, what the optimal structure and timing of a potential partnership would look like. We anticipate sharing more about our plans and priorities early next year.

鑑於進入後期乳癌試驗所需的大量投資和能力，我們已經明確表示，我們不會自行推動 BLU-222 超越這一開發階段，並一直在參與戰略合作夥伴關係討論。透過這些對話，我們正在評估 CDK2 抑制劑的新數據以及我們下一代資產的概況，以確定什麼可能是同類最佳的方法，從而確定藥物的最佳結構和時機。樣子。我們預計明年初分享更多有關我們的計劃和優先事項的資訊。

In 2024, our team has executed to both drive exceptional top-line revenue growth and prioritize our investments in our highest-value programs, laying a strong financial foundation for sustainable corporate growth. I will now turn it over to Mike to discuss our financial results.

到 2024 年，我們的團隊既要推動卓越的營收成長，又要優先投資於最高價值的項目，為永續的企業成長奠定堅實的財務基礎。我現在將把它交給麥克討論我們的財務表現。

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.

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業績，在今天的電話會議中，我將談論本季度的一些亮點。

In the third quarter, total revenues were $128.2 million from net product sales of AYVAKIT. And as mentioned earlier, we are raising our AYVAKIT product revenue guidance and now expect to achieve $475 million to $480 million in net product revenue in 2024. This updated guidance is based on continued growth in total patients on therapy, continued favorability and compliance and other factors, and stronger-than-expected performance outside of the US.

第三季度，AYVAKIT 產品淨銷售額總收入為 1.282 億美元。如前所述，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 4.75 億至 4.8 億美元。這項更新的指導意見是基於接受治療的患者總數的持續增長、持續的好感度和依從性以及其他因素，以及美國以外地區的表現強於預期。

Our gross-to-net margin remains stable in the mid-80s, and our international business is on track to break even by the end of this year.

我們的毛利率與淨利潤率保持穩定在 80 年代中期，我們的國際業務預計將在今年年底實現收支平衡。

Our total costs and operating expenses remain relatively flat at $177.2 million for the third quarter. We anticipate that both our R&D and SG&A expenses will remain relatively consistent as we close out the remainder of this year.

第三季我們的總成本和營運費用保持相對穩定，為 1.772 億美元。我們預計，隨著今年剩餘時間的結束，我們的研發和銷售、一般行政費用將保持相對穩定。

As we look ahead to 2025, our capital allocation priorities remain squarely focused on investment in our mast cell portfolio. This is to ensure that we're capturing the clear opportunity that the SM market represents with the commercialization of AYVAKIT and advancing our pipeline of other mast cell therapies to drive long-term growth in areas where our conviction around disease biology is clear. We plan to share more perspective on our 2025 capital allocation strategy early next year.

展望 2025 年，我們的資本配置重點仍集中在對肥大細胞投資組合的投資。這是為了確保我們能夠抓住 AYVAKIT 商業化所代表的 SM 市場的明確機遇，並推進我們其他肥大細胞療法的研發管線，以推動我們對疾病生物學信念明確的領域的長期增長。我們計劃在明年初就 2025 年資本配置策略分享更多觀點。

We continue to strengthen our financial position with $882.4 million in cash on hand at the end of the quarter. And importantly, we've seen our cash burn drop significantly in 2024. And we expect this trend to continue in 2025, reinforcing our clear path to financial sustainability.

我們繼續加強我們的財務狀況，截至本季末手頭現金為 8.824 億美元。重要的是，我們的現金消耗在 2024 年大幅下降。我們預計這一趨勢將在 2025 年持續下去，從而加強我們實現財務可持續性的明確道路。

With the ongoing success of the AYVAKIT launch and our commitment to disciplined investment to drive growth, we are in a great position to continue to create long-term shareholder value.

隨著 AYVAKIT 推出的持續成功以及我們對嚴格投資以推動成長的承諾，我們處於繼續創造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) Marc Frahm, TD Cowen.

（操作員說明）Marc Frahm，TD Cowen。

Hi. Thanks for taking my questions, and congrats on another strong quarter.

你好。感謝您回答我的問題，並祝賀又一個強勁的季度。

Maybe just on the ISM side to start, you're getting a meaningful number of patients out at 6, 12 months now. Any type of reauthorization criteria you're seeing or any type of maybe headlines we should expect in terms of discontinuation starting to kind of factor into the launch trajectory?

也許從 ISM 方面開始，您現在可以在 6、12 個月時讓大量患者出院。您看到的任何類型的重新授權標準或我們應該預期的任何類型的頭條新聞都開始影響發布軌跡？

And then as we get to the wild-type KIT inhibition data next year, just curious kind of where you think the thresholds are of kind of target engagement to kind of induce a response? And do you really need to kind of hit those levels clinically, or do you think more of a pulsatile or induction maintenance might be the best approach?

然後，當我們明年獲得野生型 KIT 抑制數據時，只是好奇您認為誘導反應的目標參與閾值在哪裡？您是否真的需要在臨床上達到這些水平，或者您認為更多的脈衝或感應維持可能是最好的方法？

Thanks, Marc. So Philina, maybe you can talk about what we're seeing in terms of reauthorizations for patients. And then, Fouad, I'll hand it over to you for more on BLU-808 and what we're expecting there.

謝謝，馬克。Philina，也許你可以談談我們在病人重新授權方面所看到的情況。然後，Fouad，我將把它交給您，以了解有關 BLU-808 以及我們對此的期望的更多資訊。

Yeah. Hi, Marc. As you mentioned, we are seeing a significant and growing patient base of patients on therapy, and we expect this to continue to grow.

是的。嗨，馬克。正如您所提到的，我們看到接受治療的患者數量龐大且不斷增長，我們預計這一數字將繼續增長。

In terms of reauthorizations, I think, overall, we are incredibly pleased with the strength of access that continues. We have secured and maintained strong payer coverage. We have not seen problems with reauthorization.

就重新授權而言，我認為總體而言，我們對持續的訪問強度感到非常滿意。我們已確保並維持強大的付款人覆蓋範圍。我們還沒有看到重新授權的問題。

In terms of the discontinuation rates, that remains very low. And as you know, I think the two things that continue to drive this launch is growing that strong patient base, as well as our ability to retain patients on therapy. So we're really pleased to see the trends in duration of therapy, which really connect to the potential for long-term chronic treatment.

就停藥率而言，這一比例仍然很低。如您所知，我認為繼續推動此次推出的兩件事是不斷擴大強大的患者基礎，以及我們保留患者接受治療的能力。因此，我們非常高興看到治療持續時間的趨勢，這確實與長期慢性治療的潛力有關。

And Marc, thank you for the question, on wild-type KIT, as we all know now, wild-type KIT is a very well-validated target and we have seen a lot of good work from biologics there. I think developing a small oral molecule like 808 give us the flexibility to really tune and titrate the development and the schedule of this molecule in a variety of diseases and allow us really to navigate between the inhibition of the activity and the degranulation of mast cell all the way to the depletion of mast cell. And I think having such a molecule like 808 give us that flexibility, we are happy to work with this type of small molecules.

Marc，謝謝你提出關於野生型 KIT 的問題，眾所周知，野生型 KIT 是一個經過充分驗證的靶標，我們已經看到了生物製劑的許多出色工作。我認為開發像 808 這樣的小口服分子使我們能夠靈活地真正調整和滴定該分子在各種疾病中的發育和時間表，並使我們真正能夠在活性抑制和肥大細胞脫粒之間進行導航。細胞耗竭的方法。我認為像 808 這樣的分子給我們帶來了靈活性，我們很高興與這種類型的小分子合作。

Okay. Thank you.

好的。謝謝。

Brad Canino, Stifel.

布拉德·卡尼諾，斯蒂菲爾。

Morning. Great quarter. I would actually consider this to be the most aggressive guide you've provided in terms of implied growth in forward quarters. I think feedback I've gotten from investors, and I imagine what you've heard as well, is that some of the previous guides appeared a bit too conservative. Can you help us understand how your forecasting views and abilities have changed, particularly as you think about how to incorporate variables for the 2025 guidance coming up next year? Thank you.

早晨。很棒的季度。實際上，我認為這是您在未來幾季的隱含成長方面提供的最積極的指南。我認為我從投資者那裡得到的回饋，我想你也聽到了，以前的一些指南似乎有點過於保守。您能否幫助我們了解您的預測觀點和能力發生了怎樣的變化，特別是當您考慮如何將變數納入明年即將發布的 2025 年指南時？謝謝。

Yeah. Brad, thank you. I mean, we're incredibly pleased to be at a point, at this point in the year, where we can now say that we're going to be nearing $500 million in revenue this year, which is a really tremendous place to be. And as you said, we've raised the guide. We've also tightened the range to $475 million to $480 million.

是的。布拉德，謝謝你。我的意思是，我們非常高興能夠在今年的這個時候，我們現在可以說我們今年的收入將接近 5 億美元，這確實是一個巨大的成就。正如你所說，我們已經提出了指南。我們還將範圍收窄至 4.75 億至 4.8 億美元。

But Christy, do you want to talk more about philosophy on guidance, which I know we've talked about before, and how we think about this for this year, as well as next year?

但是克里斯蒂，你想多談談指導哲學嗎？

Yeah. Thanks for the question, Brad. So our philosophy throughout the year has been to try and look at the range of variables that influence revenue, provide our best estimates on how we think what the range of outcomes on those variables may look like, and then what do we think that could imply for revenue.

是的。謝謝你的提問，布拉德。因此，我們全年的理念是嘗試研究影響收入的變數範圍，就我們如何看待這些變數的結果範圍提供最佳估計，然後我們認為這可能意味著什麼為了收入。

In the context of a launch into a category that did not exist before, a market that we are building for the first time, and the first disease-modifying therapy in that market, which is an incredible privilege and such an opportunity. So many markets -- you're fighting for market share and trying to have patients switch off of therapies, and we are really building an entirely new market opportunity, which is compelling but has its challenges, and certainly, I think, forecasting the first year of sales in that context can be a little bit difficult.

在進入一個以前不存在的類別的背景下，我們正在首次建立一個市場，並在該市場上推出第一個疾病緩解療法，這是一個令人難以置信的特權和機會。如此多的市場——你正在爭奪市場份額並試圖讓患者停止治療，而我們確實正在建立一個全新的市場機會，這是引人注目的，但也面臨著挑戰​​，當然，我認為，預測第一個在這種情況下，今年的銷售可能會有點困難。

We've definitely done our best, and we are thrilled that we have exceeded our own view, frankly, of how these variables might fall through the year. We're now in a place where we're 10 months into the year, and so we are providing a guide essentially on Q4. Our ability to forecast how we will land one quarter is obviously much tighter than when we're looking at a whole year. And so this guidance really represents our best thinking on how we will end the year, and it's really as simple as that.

我們確實已經盡力了，而且坦白說，我們對這些變數在這一年中可能會如何下降的看法超出了我們自己的看法，對此我們感到很興奮。現在距離今年已經過去 10 個月了，因此我們主要提供有關第四季度的指南。我們預測一個季度的著陸情況的能力顯然比我們預測全年的能力要嚴格得多。因此，這份指導方針確實代表了我們對如何結束這一年的最佳思考，而且就是這麼簡單。

As we go into guidance for next year, clearly, we will now be more than a year -- well more than a year into the launch, so we know this market quite well. We're still, of course, forecasting new therapy at a new market, but I think have a good sense of some of the key variables that will impact. We typically set guidance, as you know, on our Q4 call, having some early experience next year with aspects like, for example, free drug in the context of the IRA changes will be really informative and helpful to us as we think about setting that guide. But philosophy will stay the same.

當我們進入明年的指導時，很明顯，我們現在已經推出一年多了——遠遠超過一年，所以我們非常了解這個市場。當然，我們仍在預測新市場的新療法，但我認為對一些會產生影響的關鍵變數有很好的了解。如您所知，我們通常會在第四季度的電話會議上製定指導方針，明年在諸如IRA 變更背景下的免費藥物等方面獲得一些早期經驗，當我們考慮制定這一指導方針時，這對我們來說將是真正的訊息和幫助。但哲學將保持不變。

Great. Thank you.

偉大的。謝謝。

Ren Benjamin, Citizen JPM.

任本傑明，公民摩根大通。

Thanks very much, guys, for taking the questions, and congratulations on a great quarter. Can you talk a little bit about the direct-to-patient ad campaign and the new patient mentor program? How does it potentially impact SG&A, and how do you evaluate whether this is working or not? And if it isn't working, what are the other options that you have at your fingertips to grow market share?

非常感謝夥計們提出問題，並祝賀您度過了一個美好的季度。您能談談直接面向病患的廣告活動和新的病患導師計畫嗎？它對 SG&A 有何潛在影響？如果它不起作用，您還有哪些其他選擇可以增加市場份額？

Thanks, Ren, for the question. I think, first and foremost, we're at such a wonderful place in this launch where we have critical mass, where it now makes a lot of sense for us to be kind of doubling down and pushing forward on some of these direct-to-patient campaigns and initiatives that Philina talked about.

謝謝任的提問。我認為，首先也是最重要的是，我們在這次發布中處於如此美妙的位置，我們擁有臨界質量，現在對我們來說加倍努力並推進其中一些直接目標是很有意義的。談到的病患活動和倡議。

But Philina, do you want to talk a little bit about how you think about that relative to SG&A spend and the impact of these types of efforts as we look to kind of activate and educate patients?

但是 Philina，您是否想談談您對 SG&A 支出的看法，以及當我們希望激活和教育患者時這些類型的努力的影響？

Yeah. Ren, I think maybe just first off, starting at the enterprise level, we've talked about how our top priorities for investment in Blueprint's growth are really across our mast cell portfolio, including the AYVAKIT launch, elenestinib, and 808, and we will certainly look to continue to find opportunities to invest where we see the most impactful benefit in terms of return on investment.

是的。Ren，我想也許首先，從企業層面開始，我們已經討論了我們對 Blueprint 增長的投資的首要任務實際上是在我們的肥大細胞產品組合中，包括 AYVAKIT 的推出、elenestinib 和 808，我們將當然，我們會繼續尋找在投資回報方面最有影響力的投資機會。

And so in terms of how that translates into the AYVAKIT launch, you've just seen with our updated guidance that we are well on the course to deliver nearly $0.5 billion in revenue firmly on the path to achieve that peak. Conviction has never been this strong. Now is the time for us to be leaning in further into these direct-to-patient initiatives. Now that we have secured an activated and growing prescriber base that continues to grow, we have the opportunity to lean in and further engage and activate patients.

因此，就如何轉化為 AYVAKIT 的發布而言，您剛剛透過我們更新的指導方針看到，我們正在穩步實現近 5 億美元的收入，堅定地實現這一峰值。信念從未如此強烈。現在是我們進一步致力於這些直接面向患者的措施的時候了。現在，我們已經獲得了活躍且不斷增長的處方者基礎，並且還在繼續增長，我們有機會深入了解並進一步吸引和激活患者。

Why that's important is we continue to see that challenging that notion of well-controlled is critically important to open patients' aperture to what may be possible in terms of starting on a disease-modifying therapy. While patients may have become acclimated to this sense of a new normal or sort of coping with the disease and like restricting their behaviors and their activities, there's nothing more compelling than just hearing from another patient their experience on AYVAKIT and what it can feel like, how transformative that can be to reclaim what that new normal is like. And so going into those direct-to-patient initiatives, both in terms of raising awareness, talking about the importance of targeting the source of the disease and creating more of these opportunities for patients to hear from other patients, will be a critically important component of continuing to drive in this launch.

為什麼這很重要，因為我們繼續看到，挑戰良好控制的概念對於打開患者接受疾病緩解治療的可能性至關重要。雖然患者可能已經習慣了這種新常態或某種應對疾病的感覺，並且喜歡限制自己的行為和活動，但沒有什麼比從另一位患者那裡聽到他們在AYVAKIT 上的經歷及其感覺更引人注目的了，恢復新常態將帶來多大的改變。因此，開展這些直接面向患者的舉措，無論是在提高認識、談論針對疾病來源的重要性以及為患者創造更多聽取其他患者意見的機會方面，都將是至關重要的組成部分繼續推動本次發布。

Thanks, guys, and congrats.

謝謝你們，恭喜你們。

Michael Schmidt, Guggenheim.

邁克爾·施密特，古根漢。

Hi. This is Paul on for Michael. Thanks for taking our question, and congrats on the quarter.

你好。這是保羅替補邁克爾。感謝您提出我們的問題，並祝賀本季。

Just a quick one on AYVAKIT performance in third quarter. Was the sort of anticipated summer seasonality actively counterbalanced by efforts on your end, or did it simply play out less than expected? It would be great to hear your thinking on seasonality and ISM in general over the balance of the full 12 months now that you've had 1.5 years on the market.

簡單介紹一下 AYVAKIT 第三季的表現。預期的夏季季節性是否被您的努力積極抵消了，或者只是沒有達到預期？既然您已經進入市場 1.5 年，那麼很高興聽到您在過去 12 個月的時間裡對季節性和 ​​ISM 的總體看法。

And then my second one is just on BLU-808 and early signals of activity that we might see. How do you think about some of the classic markers like mast cell depletion and tryptase reduction for the oral agent compared to what's been shown by the KIT antibodies? And what's the right way to think about correlation between those biomarkers and clinically relevant endpoints like the [urinary] activity score? Thank you.

然後我的第二個是關於 BLU-808 和我們可能看到的早期活動訊號。與 KIT 抗體所顯示的結果相比，您如何看待口服藥物的一些經典標記物，例如肥大細胞消耗和類胰蛋白酶減少？思考這些生物標記與臨床相關終點（如[排尿]活動評分）之間的相關性的正確方法是什麼？謝謝。

Yeah. Thanks, Paul. There's a lot in that. So maybe Philina, if you could take the first piece, and then we'll hand it to Fouad.

是的。謝謝，保羅。其中有很多內容。所以也許菲莉娜，如果你能拿走第一塊，然後我們會把它交給福阿德。

One thing I would just say is that the commentary that we have been making around -- as we think about new patient starts since before we even launched is this is a rare disease and we expect there to be variability and lumpiness on a week-by-week type of basis. But over the longer perspective, we continue to believe there'll be strong and steady growth in patients on therapy.

我想說的一件事是，我們一直在進行的評論 - 當我們在推出之前就開始考慮新患者時，這是一種罕見的疾病，我們預計一周內會出現變異和塊狀現象- 週類型的基礎。但從長遠來看，我們仍然相信接受治療的患者人數將會強勁且穩定地成長。

And the commentary made on the last quarter was that this is not about if patients start, it's about when. And I think what has been really clear is both of those things have played out exactly as we have described.

上個季度的評論是，這不是關於患者是否開始，而是關於何時開始。我認為非常清楚的是，這兩件事的發展完全正如我們所描述的。

So Philina, would you like to talk more about that?

菲莉娜，你想多談談這個嗎？

Yeah. So I think Kate teed it up really well. We've alluded to some of the short-term quarterly dynamics that can impact a particular quarter. We know that holidays have the potential to impact the timing of patient starts to go to the next visit.

是的。所以我認為凱特做得很好。我們已經提到了一些可能影響特定季度的短期季度動態。我們知道假期可能會影響患者開始下次就診的時間。

What we saw in the third quarter is that our team has done an incredible job managing through these dynamics with a strong increase of demand through the back half of the year. But I think most importantly sort of lasering out from the quarter to quarter is really that year-over-year trajectory. And we can see from the updated guidance we are on a path to deliver over 100% growth year over year. And again, I think that places us firmly on the path of marching towards that greater than $2 billion peak.

我們在第三季看到的是，我們的團隊在管理這些動態方面做得非常出色，下半年需求強勁成長。但我認為最重要的是逐季度的大幅成長實際上是逐年成長的軌跡。從更新後的指導中我們可以看到，我們正走在逐年增長超過 100% 的道路上。我再次認為，這使我們堅定地走在邁向超過 20 億美元高峰的道路上。

And then Fouad, do you want to talk a little bit about wild-type KIT and what we're thinking about from a biomarker and correlation perspective?

然後，Fouad，您想談談野生型 KIT 以及我們從生物標記和相關性角度思考的問題嗎？

Yeah. Thank you, Paul, for the question. We are developing the small molecule, as I said earlier answering Marc's question, with the idea that with a small molecule we can really tune the dosing on the schedule to really navigate the wide range of the activity of the mast cell and target a number of type 2 inflammatory diseases.

是的。謝謝保羅提出這個問題。正如我之前回答馬克問題時所說，我們正在開發小分子，我們的想法是，透過小分子，我們可以真正調整時間表上的劑量，以真正駕馭肥大細胞的廣泛活動並靶向許多細胞。型發炎性疾病。

As Christy mentioned, we anticipate to report the data early from the SAD-MAD study early in 2025. And we'll look at overall subject safety. We'll look at our pharmacology. We expect the pharmacology to be a very good one and really allowing us to do the tunability and the titration that I talked about earlier. And we will report a number of biomarkers, including the level of tryptase.

正如 Christy 所提到的，我們預計將於 2025 年初報告 SAD-MAD 研究的數據。我們將關注整體受試者安全性。我們將看看我們的藥理學。我們期望藥理學是一個非常好的藥理學，並且真正允許我們進行我之前談到的可調性和滴定。我們將報告許多生物標記物，包括類胰蛋白酶水平。

More specifically to your question, tryptase is a supportive pharmacodynamic marker for the activity of the agents and varies from disease to another. So we would like to see tryptase decrease in these healthy volunteers. We also know that in some more complex diseases where there is already a POC, like chronic urticaria, tryptase is a part of the story but in a much more complex environment.

更具體地說，對於您的問題，類胰蛋白酶是藥物活性的支持性藥效標記物，並且因疾病而異。因此，我們希望看到這些健康志願者的類胰蛋白酶減少。我們也知道，在一些已經存在 POC 的更複雜的疾病中，例如慢性蕁麻疹，類胰蛋白酶是其中的一部分，但環境要複雜得多。

As an example, when we go to type 2 asthma, diseases are more complex than just looking at the tryptase. We can look at other markers. So we have the opportunity to share data with tryptase and beyond tryptase.

舉個例子，當我們研究第 2 型氣喘時，疾病比僅僅看類胰蛋白酶更複雜。我們可以看看其他標記。因此，我們有機會與類胰蛋白酶以及類胰蛋白酶以外的領域分享數據。

And this is where I -- maybe I'll just plug in again for our seminar coming up November 14, where we'll talk more about how we're thinking about 808 in our overall kind of development strategy in mast cell. So please do tune in if you can.

這就是我——也許我會再次參加 11 月 14 日舉行的研討會，我們將更多地討論我們如何在肥大細胞的整體開發策略中考慮 808。所以，如果可以的話，請收聽。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Thanks for taking our question. This is Tammie on for Salveen, and congrats on the quarter.

感謝您提出我們的問題。這是 Salveen 的 Tammie，恭喜本季。

So to follow up from some of the previous questions on 808, overall, how derisking do you think that the healthy volunteer data will be with regard to navigating a therapeutic window? And what's your view on the differentiation here from strategies such as MRGPRX2?

那麼，從先前關於 808 的一些問題來看，總體而言，您認為健康志願者數據對於導航治療窗口的風險有多大？您對 MRGPRX2 等策略的差異化有何看法？

And then just one on ISM. As we look to 2025, maybe lay out some of the moving parts that we should be aware here, especially as ex-US starts to play a larger role. Thank you.

然後只有一篇關於 ISM 的文章。當我們展望 2025 年時，也許會列出一些我們應該注意的變化部分，特別是當美國以外的國家開始發揮更大的作用時。謝謝。

Yes, thank you very much for the question. Fouad will talk about 808, and of course, we'll be talking more about 2025 on the Q4 call, but maybe you can just give a high level on that.

是的，非常感謝你的提問。Fouad 將談論 808，當然，我們將在第四季度電話會議上更多地談論 2025 年，但也許你可以對此進行高水準的討論。

So from an 808 perspective, our development strategy is really to target wild-type KIT to fine-tune the mast cell and go to a variety of diseases.

所以從808的角度來看，我們的開發策略確實是針對野生型KIT來微調肥大細胞，去多種疾病。

In terms of derisking, to your question, if we look today at wild-type KIT POC, I think biologics did a very good job showing a strong proof of concept in chronic urticaria [subcutaneous] and also cold-induced. Therefore, the data that we anticipate to share early in 2025 will be a major inflection point for us and for patients to really benefit from what we hope and expect to be a good drug profile for 808.

就您的問題而言，就消除風險而言，如果我們今天看看野生型KIT POC，我認為生物製劑做得非常好，在慢性蕁麻疹（皮下）和寒冷誘發的蕁麻疹方面展示了強有力的概念證明。因此，我們預計在 2025 年初分享的數據將成為我們和患者真正受益於我們希望和期望的 808 良好藥物概況的一個主要轉折點。

Now, there is a lot of room to improve from the overall therapeutic index for these therapies. And we believe having a small molecule that we can fine-tune with completely different type of pharmacology from biologics will help us achieve such a goal, not only in chronic urticaria, but in a variety of diseases. And as Kate mentioned earlier, we will talk about these diseases at our seminar in a few weeks.

現在，這些療法的整體治療指數還有很大的進步空間。我們相信，擁有一種可以與生物製劑完全不同類型的藥理學進行微調的小分子將有助於我們實現這一目標，不僅在慢性蕁麻疹方面，而且在多種疾病方面。正如凱特之前提到的，我們將在幾週後的研討會上討論這些疾病。

Regarding your question on different mast cell targets, and much specifically MRGPRX2, there are a number of targets on the mast cell. We believe, and as the scientific community does too, that such a target is probably organ restricted potentially to the skin. And we need to see more clinical data because, I mean, it's a really data-free zone, if I can use this analogy.

關於您關於不同肥大細胞標靶的問題，特別是 MRGPRX2，肥大細胞上有許多標靶。我們相信，科學界也相信，這樣的目標可能是只限於皮膚的器官。我們需要看到更多的臨床數據，因為，我的意思是，如果我可以使用這個類比的話，這確實是一個沒有數據的區域。

On our strategy, by going to wild-type KIT, we know that we will target the mast cell wherever it is, either in the lung or in the gut or in the skin. And so we believe going after the inhibition of wild-type KIT is a much broader strategy than other targets.

根據我們的策略，透過使用野生型 KIT，我們知道我們將靶向肥大細胞，無論它在哪裡，無論是在肺部、腸道或皮膚中。因此，我們相信抑制野生型 KIT 是比其他目標更廣泛的策略。

Yeah. And then Christy, do you want to talk a little bit about, just at a high level, what we think about 2025? Obviously, we'll spend a lot more time with you all on this going into next year.

是的。然後克里斯蒂，您想從高層次談談我們對 2025 年的看法嗎？顯然，明年我們將花更多時間與大家一起討論這個問題。

Yeah. So we'll provide guidance, again, on the Q4 call. I think the variables that we'll be thinking about are going to be broadly very similar to sort of what we've been talking about this year.

是的。因此，我們將在第四季度的電話會議上再次提供指導。我認為我們將考慮的變數將與我們今年討論的變數大致非常相似。

At a macro level, what's driving this launch is new patients starting on therapy and keeping those patients on therapy over time. And what, of course, is becoming more and more important as we progress through the launch is we now have a very substantial number of patients being treated with AYVAKIT that we will be carrying into next year and then, of course, growing from that base. We'll have new markets coming on internationally, as you mentioned, as we negotiate pricing and reimbursement and move through additional launches.

從宏觀層面來看，推動此次推出的原因是新患者開始接受治療，並隨著時間的推移讓這些患者繼續接受治療。當然，隨著我們推出的進展，變得越來越重要的是，我們現在有大量患者正在接受 AYVAKIT 治療，我們將在明年繼續使用這些患者，當然，還會在此基礎上不斷增長。正如您所提到的，當我們協商定價和報銷並推出更多產品時，我們將在國際上出現新的市場。

Every year has its own factors. I'm sure we'll talk a bit about free drugs, IRA impacts, et cetera, as we get into next year and sort of see how the first couple months of the year play out. But the big picture, again, is that we are in the early innings of a launch with a substantial amount of room for continued growth. And look forward to providing more on that view as we get into next year.

每一年都有它自己的因素。我確信，當我們進入明年時，我們會討論免費藥物、愛爾蘭共和軍的影響等等，看看今年的前幾個月會如何發展。但總體情況是，我們正處於產品發布的早期階段，還有很大的持續成長空間。並期待在明年我們能提供更多關於這一觀點的資訊。

Derek Archila, Wells Fargo.

德里克·阿奇拉，富國銀行。

Hey. Good morning, and congrats on the updates here and on the quarter. Just two, one clarifying and then just one question.

嘿。早上好，恭喜此處和本季的更新。只有兩點，一是澄清，然後是一個問題。

So just on 3Q relative to the second quarter, just in terms of the net patient adds, I guess what does that look like Q over Q? And then I guess in terms of the seasonal factor here, can you kind of just kind of give us some qualitative information on the magnitude and how it might impact 4Q?

因此，就第三季相對於第二季而言，就淨患者增加而言，我猜這看起來像 Q 與 Q 相比？然後我想就季節性因素而言，您能否向我們提供一些有關其影響程度及其如何影響第四季度的定性資訊？

And then just on 808, you guys have been talking a lot about it on the call, very exciting. I guess is your expectation tryptase reductions in line with antibodies and safety better than the antibody? Or how do you think the overall profile will look when all is said and done? Thanks.

然後就在 808 上，你們在電話中談論了很多，非常令人興奮。我猜您期望的類胰蛋白酶減少是否與抗體一致且安全性比抗體更好？或者說，當一切都說完了之後，你認為整體形象會是什麼樣子？謝謝。

Yeah. Thanks, Derek, for the question. So Philina, as we moved away from talking about kind of that projected estimated number on therapy at the end of the quarter last year, Derek, but we can certainly provide kind of qualitative commentary around how we're thinking about seasonality and what we've seen there. And I know we've touched on that, but Philina, do you want to kind of reiterate there how you're thinking about seasonality?

是的。謝謝德里克提出的問題。所以，菲利娜，當我們不再討論去年季度末預計的治療人數時，德里克，但我們當然可以就我們如何看待季節性以及我們的內容提供定性評論。我知道我們已經談到了這一點，但是 Philina，您想重申您對季節性的看法嗎？

Yeah. I think I would just reiterate by starting with the expectation that we continue to expect strong and steady growth in the number of patients on therapy. This is what we have always said. There might be variations month to month based on factors like holidays. We know that in Q4, for example, there are fewer business days.

是的。我想我想重申一下，首先我們預計接受治療的患者數量將繼續強勁而穩定地增長。這是我們一直在說的。由於假期等因素，每月可能會有變化。例如，我們知道第四季的工作日較少。

But I think maybe going back to what Christy just articulated, the most important piece that's driving this launch is that continued growth in patients on therapy, strong and steady. Quarters are going to be more steady than months in a rare disease launch such as this one. And most importantly, the arc of that overall trajectory is that we're showing significant growth on a year-to-year basis, significant headroom to continue to grow, and we're really focused on marching towards that peak potential.

但我認為也許回到克里斯蒂剛剛闡述的內容，推動此次推出的最重要因素是接受治療的患者人數持續強勁且穩定地成長。在像本次這樣的罕見疾病推出中，季度將比幾個月更加穩定。最重要的是，整體軌蹟的弧線是，我們每年都顯示出顯著的增長，繼續增長的空間很大，而且我們真正專注於邁向峰值潛力。

And I think, Derek, now that we're kind of coming into like the end of our first full year of launch, we have a lot of confidence around the dynamics that we see in any given quarter. And those are, as I said in my prepared remarks, like dynamics that everyone faces, dynamics that are specific to rare diseases, and those that are unique to SM.

我認為，德里克，現在我們已經進入了發布的第一個完整年度的尾聲，我們對任何特定季度看到的動態充滿信心。正如我在準備好的演講中所說，這些就像每個人都面臨的動態、罕見疾病特有的動態以及 SM 獨有的動態。

And I think we now have shown and demonstrated that our team is able to understand those and work through those in a very constructive way. The goal here is to move towards a $2 billion plus product, and we're going to do that year by year. So that is our focus and will continue to be our focus.

我認為我們現在已經表明並證明我們的團隊能夠理解這些問題並以非常有建設性的方式解決這些問題。我們的目標是推出價值超過 20 億美元的產品，我們將年復一年地實現這一目標。所以這是我們的重點，並將繼續是我們的重點。

And then Fouad, do you want to talk a little bit about BLU-808 and how you're thinking about that relative to what we've seen from some of the data that's come out from the antibody approach?

然後，Fouad，您想談談 BLU-808 嗎？

Yeah. I think, clearly the data from the antibody approaches validates the target specifically in two subsets of urticaria, which is chronic spontaneous urticaria and cog-induced urticaria, which is a really good thing. And as I mentioned earlier, this makes our SAD and MAD data report, and we anticipate early next year, extremely important and a major inflection point for patients and for Blueprint Medicines.

是的。我認為，顯然，抗體方法的數據特別驗證了蕁麻疹的兩個子集的目標，即慢性自發性蕁麻疹和齒輪誘發的蕁麻疹，這是一件非常好的事情。正如我之前提到的，這使得我們的 SAD 和 MAD 數據報告（我們預計明年初）對於患者和 Blueprint Medicines 來說非常重要，也是一個主要的轉捩點。

Developing a small molecule in this area gives us the opportunity to really navigate the targeting of mast cell all the way from depleting the mast cell when we need to do that to inhibiting the activation and the degranulation without getting full depletion. It will allow us also to have a very good therapeutic index by, on one hand, having activity on the disease and on the other hand not reaching that far and that deep to myeloid progenitor to generate adverse events of toxicity that we don't need to.

在這一領域開發小分子使我們有機會真正引導肥大細胞的靶向，從我們需要時耗盡肥大細胞到抑制激活和脫顆粒而不完全耗盡。它也將使我們能夠擁有非常好的治療指數，一方面對疾病有活性，另一方面不會到達骨髓祖細胞那麼遠和那麼深，從而產生我們不需要的毒性不良事件到。

It is very difficult to do with biologics. We believe our strategy with a small molecule is very differentiated and will allow us to fine-tune and titrate and achieve these goals.

用生物製劑來做到這一點非常困難。我們相信我們的小分子策略非常與眾不同，將使我們能夠進行微調和滴定並實現這些目標。

Mike Ulz, Morgan Stanley.

麥克烏爾茲，摩根士丹利。

Good morning. Thanks for taking the question, and congrats on the quarter as well. Maybe just on the AYVAKIT, you highlighted sort of strength OUS and being better than expected. Maybe you could provide some more color there and how you expect those trends to sort of evolve as we get into next year. Thanks.

早安.感謝您提出問題，也恭喜本季。也許就在 AYVAKIT 上，您強調了 OUS 的某種優勢並且比預期更好。也許您可以在那裡提供更多的顏色，以及您期望這些趨勢在我們進入明年時如何演變。謝謝。

Yeah. Thanks, Mike. We're incredibly pleased with how the international launch has been going, and the team has done just a tremendous job in terms of kind of delivering well beyond expectations.

是的。謝謝，麥克。我們對國際發布的進展感到非常滿意，團隊在交付方面做得非常出色，遠遠超出了預期。

And Christy, I don't know if you want to talk a little bit more about that international launch.

克里斯蒂，我不知道你是否想多談談這次國際發表會。

Yes, we were really, really pleased with the strength of the quarter. Of course, we talk a lot about Germany, which is the first out of the gate on ISM and where we've seen, as Philina said, dynamics that look very similar to the US in terms of uptake, which has been really gratifying to see, including prescribing coming from both academic centers and in the community. So very, very similar dynamics.

是的，我們對本季的強勁表現感到非常非常滿意。當然，我們談論了很多關於德國的事情，德國是第一個走出 ISM 大門的國家，正如菲利娜所說，我們看到德國的動態在採用方面與美國非常相似，這確實令人欣慰。 請參閱，包括來自學術中心和社區的處方。非常非常相似的動態。

And in the quarter, what we saw was the strength of that uptake really overcoming some of the price headwinds that we had referred to. Of course, we're still working through the process with negotiations in Germany, and we'll have a sense of where that lands early next year. But the demand growth is really more than offsetting that, which has been great to see. And then, of course, we continue to see growth in other markets, which are still launching in advance of them.

在本季度，我們看到這種吸收的力量確實克服了我們提到的一些價格阻力。當然，我們仍在與德國進行談判，我們將在明年初了解其進展。但需求成長確實足以抵消這一影響，這一點令人高興。當然，我們繼續看到其他市場的成長，這些市場仍然先於它們推出。

As we get into next year, we expect to see more of the major markets in Europe start to come online as we work through ISM pricing negotiations. So we've talked about international being an important driver of top-line revenue growth. I expect that to continue. Of course, the US will represent the lion's share of the opportunity in the short term, but we would expect international to continue to become a more and more important part of the opportunity. And certainly when we think about the peak, we're excited about the potential we see both in the US, as well as outside the US.

進入明年，我們預計隨著 ISM 定價談判的進行，歐洲更多主要市場將開始上線。因此，我們已經討論過國際化是營收成長的重要驅動力。我希望這種情況能夠持續下去。當然，短期內美國將佔據最大的機遇，但我們預期國際將繼續成為機會中越來越重要的一部分。當然，當我們想到高峰時，我們對在美國以及美國以外看到的潛力感到興奮。

And then one thing to add to that, in Mike's commentary, he mentioned that actually at the end of this year our international organization is going to break even. And so this team is really driving kind of tremendous top-line growth in a very financially efficient and disciplined way. So that is -- I think that's a great place for us to be.

然後補充一點，在麥克的評論中，他提到實際上到今年年底我們的國際組織將實現收支平衡。因此，這個團隊確實以一種非常經濟高效和紀律嚴明的方式推動了巨大的營收成長。所以我認為這對我們來說是一個很棒的地方。

Great. Thank you.

偉大的。謝謝。

Ami Fadia, Needham.

阿米法迪亞，尼達姆。

Hi. Good morning. Congrats on the nice quarter. Two quick questions. Firstly, on an estimate would be Part 2 of the HARBOR study initiating by the end of the year. Can you talk about how your development strategy differs from that of AYVAKIT and how do you see it being differentiated from AYVAKIT?

你好。早安.恭喜這個美好的季度。兩個簡單的問題。首先，據估計，HARBOR 研究的第二部分將在今年底啟動。您能否談談您的發展策略與 AYVAKIT 有何不同？

And with regards to BLU-808, the tunability of a small-molecule strategy, I think you've sort of talked about quite a bit in the Q&A. As we see the data from the healthy volunteer study -- dose escalation study, how would you take that information and then think about the different diseases where you could apply it? And maybe sort of what are some of the indications that you're thinking about taking it into from initial thoughts? That would be helpful. Thank you.

關於 BLU-808，即小分子策略的可調性，我認為您在問答中已經談論了很多。當我們看到來自健康志願者研究——劑量遞增研究的數據時，您將如何獲得這些信息，然後考慮可以應用它的不同疾病？也許有哪些跡象表明您正在考慮從最初的想法中考慮這一點？那會有幫助的。謝謝。

Yeah. Thank you, Ami. And I think maybe we'll start -- I'll hand -- Christy can talk a little bit more about elenestinib and Fouad will take the question about BLU-808.

是的。謝謝你，阿米。我想也許我們會開始——我會——Christy 可以多談談 elenestinib，Fouad 將回答有關 BLU-808 的問題。

I think just stepping back for one moment is that the position we're in at Blueprint Medicines with AYVAKIT becoming the standard of care and a durable leader across advanced SM and ISM and then the opportunity we now have to bring elenestinib forward to really maximize the longer-term performance and innovation across the SM franchise is really a unique and incredible position.

我想先退後一步，我們在 Blueprint Medicines 所處的位置是，AYVAKIT 成為護理標準，並且是先進 SM 和 ISM 領域的持久領導者，然後我們現在有機會將 elenestinib 向前推進，以真正最大化SM特許經營權的長期績效和創新確實是一個獨特且令人難以置信的地位。

Do you want to talk a little bit, Christy, about how we're thinking about bringing ele forward to do just that?

克里斯蒂，你想談談我們如何考慮讓 ele 來做到這一點嗎？

Yeah. So as Kate has said, our strategy with elenestinib is really to extend a franchise that we think is incredibly important both for patients and for Blueprint as we get into really the next decade and beyond. This is an opportunity that we are growing into and we think we have a significant amount of headroom in SM to continue to grow.

是的。因此，正如 Kate 所說，我們對 elenestinib 的策略實際上是擴大特許經營權，我們認為，隨著我們進入下一個十年及以後，這對患者和 Blueprint 都非常重要。這是我們正在成長的機會，我們認為 SM 有很大的空間可以繼續發展。

Our expectation is that AYVAKIT will be the durable market leader for quite some time and will be growing for years to come. And the value of elenestinib is really to be able to bring a therapy that delivers additional differentiated clinical impact over the long term so that we can continue to drive growth in the franchise into the latter part of the next decade.

我們的預期是，AYVAKIT 將在相當長的一段時間內成為持久的市場領導者，並將在未來幾年持續成長。elenestinib 的價值實際上在於能夠帶來一種能夠在長期內提供額外差異化臨床影響的療法，以便我們能夠在下一個十年的後半段繼續推動該系列產品的成長。

And so we will be initiating Part 2 of HARBOR. We'll obviously share more about what the design of that study looks like. But we know that the only way that you get to extend the value of a franchise like this is by delivering clinical differentiation. We understand more about the full manifestations of the disease now and much more about that than we did 5 or 10 years ago. And so I think our ability to measure clinical impact and really demonstrate what a targeted therapy can do in this space is different now than it was when we started the PIONEER study.

因此，我們將啟動 HARBOR 的第二部分。顯然，我們將分享更多有關該研究設計的資訊。但我們知道，擴大此類特許經營價值的唯一方法是提供臨床差異化。我們現在對這種疾病的全部表現有了更多的了解，而且比 5 或 10 年前也了解更多。因此，我認為我們現在衡量臨床影響並真正證明目標治療在這個領域的作用的能力與我們開始 PIONEER 研究時不同。

So in terms of what the actual design of HARBOR will look like, we'll obviously have more to say about that as we open the study. And again, I would point everybody to our mast cell webinar that we have scheduled on November 14, where we're planning on sharing more about our development strategy across our mast cell portfolio.

因此，就港口的實際設計而言，當我們開始研究時，我們顯然會有更多話要說。再次，我想向大家介紹我們定於 11 月 14 日舉行的肥大細胞網路研討會，我們計劃在會議上分享更多有關我們肥大細胞產品組合的開發策略的資訊。

Thank you, Christy, and thank you, Ami, for the question. So your first question is really how would the data from the SADMAD study help us understand the tunability profile of 808?

謝謝克里斯蒂，也謝謝阿米提出的問題。所以你的第一個問題其實是 SADMAD 研究的數據如何幫助我們了解 808 的可調性概況？

I would say, as we all know, SADMAD study, we are exploring a number of doses, a variety of cohorts of patients over time, and we are also looking at pharmacodynamic markers. So when we look at the totality of the pharmacology and the data in healthy volunteers at a variety of doses of a different level of inhibition and their impact on the pharmacodynamic marker, it will give us really a good understanding of how we can develop tunable and titrable schedules for a variety of diseases.

我想說的是，眾所周知，在 SADMAD 研究中，我們正在探索多種劑量、一段時間內的各種患者隊列，我們也在研究藥效學標記。因此，當我們查看健康志願者在不同劑量的不同抑製水平下的藥理學和數據的整體性及其對藥效標記物的影響時，這將使我們真正更好地了解如何開發可調節和針對多種疾病的滴定時間表。

For the second part of your question on what is the breadth in terms of number of diseases and what other diseases we'll go to, I think we're targeting type 2 inflammation in a broad way. We'll have the opportunity in a few weeks from now at our seminar to talk really about these diseases and how we think about them. But you can think about really targeting a broad variety of type 2 inflammation. How we will do it, as we mentioned in the past, is through some or a number of POC cohorts or studies to really, early on, see the activity across a wide range of diseases and start step-by-step derisking 808 toward the selection of the major indication for registrational development.

對於你的問題的第二部分，即疾病數量的廣度以及我們將討論哪些其他疾病，我認為我們正在廣泛地針對 2 型發炎。幾週後我們將有機會在我們的研討會上真正討論這些疾病以及我們如何看待它們。但您可以考慮真正針對多種 2 型發炎。第 808 章選擇註冊開發的主要適應症。

[Marcus Schreider], Oppenheimer.

[馬庫斯·施雷德]，奧本海默。

Hi. This is Marcus on for Matt. Thank you for taking the questions. You've shown already some nice preclinical data on asthma. Is it fair to say that this will be one of your focus there?

你好。這是馬庫斯替馬特發言。感謝您提出問題。您已經展示了一些關於氣喘的不錯的臨床前數據。可以公平地說，這將是您在那裡的重點之一嗎？

Great question. Obviously, asthma, type 2 asthma, more precisely, is one of the key type 2 inflammatory diseases. We'll be looking at the range of these diseases. Obviously, I think in a matter of a few weeks, we'll be able to get in a little bit more specific about the diseases. But I mean, it is safe to say that many diseases in the type 2 inflammation range or area will be part of our thinking.

很好的問題。顯然，氣喘，更準確地說，是2型氣喘，是關鍵的2型發炎性疾病之一。我們將研究這些疾病的範圍。顯然，我認為在幾週內，我們將能夠更具體地了解這些疾病。但我的意思是，可以肯定地說，2 型發炎範圍或區域的許多疾病將成為我們思考的一部分。

Peter Lawson, Barclays.

彼得·勞森，巴克萊銀行。

Great. Thank you. Thanks for the update. Really appreciate it.

偉大的。謝謝。感謝您的更新。真的很感激。

On slide 6 for your data around breadth and depth, just the -- I thought it was an interesting dynamic, the number of physicians with greater than 10 patients. Just wondering if you could kind of talk through that, if there's room to grow there, if this is how -- if that's how it kind of plateaus out, or if there's ability to grow beyond greater than 10 patients, and if these are centers of excellence. Thank you.

在第 6 張投影片中，關於廣度和深度的數據，我認為這是一個有趣的動態，即治療超過 10 名患者的醫生數量。只是想知道你是否可以談談這個問題，那裡是否有增長的空間，是否是這樣的——是否是這樣的，是否會趨於穩定，或者是否有能力增長到超過10 名患者，以及這些是否是中心卓越的。謝謝。

Yeah. Thank you for the question, Peter. And as Philina has -- as we've been saying this kind of across the launch, the breadth and depth dynamics that we're seeing here have just been a tremendous strength in the launch, and that graph is a snapshot of some of the providers.

是的。謝謝你的提問，彼得。正如 Philina 所言——正如我們在整個發布過程中所說的那樣，我們在這裡看到的廣度和深度動態是發布過程中的巨大優勢，該圖是一些內容的快照。

But Philina, do you just want to talk about our opportunity, as I know that we continue to believe will drive quite a bit of depth as well?

但是菲莉娜，你只想談談我們的機會嗎？

Yeah. Peter, to your question, I think the bottom line is significant headroom to grow across all metrics and measures that we see across this market in both providers and patients. So if we look at our provider base, so we're really excited to see the uptick in the number of providers who are treating 10 or more patients.

是的。彼得，對於你的問題，我認為最重要的是，我們在這個市場上看到的提供者和患者的所有指標和措施都有巨大的成長空間。因此，如果我們看看我們的提供者基礎，我們真的很高興看到正在治療 10 名或更多患者的提供者數量增加。

Again, that, even within those top 400 providers, substantial headroom to continue to grow and treat more patients on therapy within those top 400, as I said on the call, that's just a tiny part of the picture. There are additional -- many additional providers across that top 400 as well, where we continue to see growing breadth as well as depth. And we haven't even really yet explored the potential of additional specialties such as dermatology and others who are treating the broader constellation of patients based on their symptomology.

再次強調，即使在這400 家頂級醫療服務提供者中，也有巨大的空間來繼續發展並治療更多在這400 家頂級醫療服務提供者中接受治療的患者，正如我在電話會議上所說，這只是整個情況的一小部分。前 400 強中還有許多其他供應商，我們繼續看到這些提供者的廣度和深度都在不斷增長。我們甚至還沒有真正探索其他專業的潛力，例如皮膚科和其他根據症狀治療更廣泛患者群體的專業。

So bottom line, significant headroom to grow. And we're confident that places us on a path to achieve really more than $2 billion peak.

因此，最重要的是，成長空間很大。我們相信，這將使我們走上真正實現超過 20 億美元高峰的道路。

Laura Prendergast, Raymond James.

勞拉·普倫德加斯特，雷蒙德·詹姆斯。

Hey, guys. Congrats on the great quarter. So I know you said you expect pre-drug dynamics to generally remain steady below 20% or mid-teens, as you said, on average. But are you seeing or do you expect any month-to-month or quarter-to-quarter variability in these dynamics?

嘿，夥計們。恭喜這個偉大的季度。所以我知道您說過，您預計用藥前動態通常會穩定在 20% 或十幾歲左右，正如您所說，平均而言。但是您是否看到或預期這些動態會出現每月或每季的變化？

And then just a quick second question for me. Any guidance on how to think about gross margin moving forward? Thanks.

然後問我第二個問題。關於如何考慮未來毛利率有什麼指引嗎？謝謝。

Yeah. So thank you, Laura, for those questions. Philina, do you want to talk about how we're thinking about pre-drug as we close out this year? Of course, this is all reset in 2025. And as Christy mentioned, we're going to be paying close attention to that in January as we look at the impacts of the rest of the IRA.

是的。勞拉，謝謝你提出這些問題。菲莉娜，你想談談我們在今年結束時如何看待戒毒前的事情嗎？當然，這一切都在2025年重置。正如克里斯蒂所提到的，我們將在一月份密切關注這一點，因為我們將研究愛爾蘭共和軍其他成員的影響。

But Philina, how do you want to think about it for the rest of this year?

但是菲莉娜，今年剩下的時間你想怎麼想？

Yeah. Laura, so we've talked about how, launch to date, the proportion of patients on free drug has reached the mid-teens. That has been relatively consistent over the past couple quarters. And we expect that to remain consistent through the end of this year.

是的。勞拉，我們已經討論過，到目前為止，接受免費藥物的患者比例已達到十幾歲。在過去的幾個季度中，這一情況相對穩定。我們預計到今年年底這一情況將保持一致。

As Kate alluded to, I think one thing we'll want to keep our eye on is this resets next year due to the changes in sort of Part D from the IRA. And really, at this point, we have such a substantial patient base on therapy that small changes in these factors like free drug can have impacts on revenue. So another piece to look at, along with all the other variables that Christy alluded to, that will influence how we think about 2025.

正如凱特所提到的，我認為我們需要關注的一件事是，由於愛爾蘭共和軍 D 部分的變化，明年會重置。事實上，在這一點上，我們有如此龐大的接受治療的患者基礎，免費藥物等這些因素的微小變化可能會對收入產生影響。因此，另一件值得關注的事情，以及克里斯蒂提到的所有其他變量，將影響我們對 2025 年的看法。

And Mike, do you want to talk a little bit about the gross margin question that Laura had?

麥克，你想談談勞拉提出的毛利率問題嗎？

Yeah. Thanks, Laura. Just with respect to gross margin, first of all, we think we are in a solid position with AYVAKIT. We have relatively low cost of goods sold, and so we expect our gross margins to be high and remain really relatively stable at this point in the launch that we have enough volume coming through.

是的。謝謝，勞拉。就毛利率而言，首先，我們認為 AYVAKIT 的地位穩固。我們的銷售成本相對較低，因此我們預計我們的毛利率會很高，並且在推出時保持相對穩定，因為我們有足夠的銷售量。

We do see some variation due to sales of product to partners like CStone. So month -- or quarter to quarter, sorry, you might see some variability. But fundamentally, we expect margins to be stable and strong.

由於向基石藥業等合作夥伴銷售產品，我們確實看到了一些變化。因此，每個月或每個季度，抱歉，您可能會看到一些變化。但從根本上講，我們預計利潤率將穩定且強勁。

Great. Thank you very much.

偉大的。非常感謝。

David Lebowitz, Citi.

大衛‧勒博維茨，花旗銀行。

Thank you very much for taking my questions. I have two for you. First, on physician mix, in the past, you've broken down the academic versus community doctors. If you could just update us on that -- update on that in case I missed it.

非常感謝您回答我的問題。我有兩個給你。首先，在醫生組合方面，過去，您已經將學術醫生與社區醫生進行了細分。如果你能告訴我們最新的情況——更新一下，以防我錯過了。

And then number two, I just wanted to ask about elenestinib and the HARBOR 2 trial that's being studied in ISM. I know it's getting underway soon. A competitive therapy out there is studying it, but also in ISM and smoldering mastocytosis. I'm just curious as to why it would be ISM only as opposed to including ESM patients. Thanks for taking my questions.

第二，我只是想問 elenestinib 和 ISM 正在研究的 HARBOR 2 試驗。我知道它很快就會開始。一種競爭性療法正在研究它，但也在 ISM 和悶燒性肥大細胞增多症中進行研究。我只是好奇為什麼只包括 ISM 而不是包括 ESM 患者。感謝您回答我的問題。

Yeah. Thanks, David. And maybe, Philina, you could just talk about the mix of physicians, and then I'll hand it to Fouad to talk a little bit more about elenestinib and how we're thinking about the kind of inclusion criteria there.

是的。謝謝，大衛。Philina，也許你可以只討論醫生的組合，然後我將把它交給 Fouad 來更多地討論 elenestinib 以及我們如何考慮那裡的納入標準。

Yeah. So one of the most important leading indicators is the prescriber base, which continues to grow for AYVAKIT. We see that across all specialties and settings. So in terms of the mix, continues to be pretty evenly split between the academic and community setting. We continue to see additional hemoncs, as well as allergist immunologists, trying AYVAKIT for the first time. And as they have that first positive experience, going on to repeat prescribe and really broadening the lens on the patients that they see as addressable for treatment.

是的。因此，最重要的領先指標之一是 AYVAKIT 的處方者基礎，該基礎持續成長。我們在所有專業和環境中都看到了這一點。因此，就混合而言，學術和社區環境之間的比例仍然相當均勻。我們繼續看到更多的血液學家以及過敏免疫學家首次嘗試 AYVAKIT。當他們有了第一次積極的經歷時，就會繼續重複開處方，並真正擴大他們認為可以接受治療的患者的視野。

And importantly, we're really encouraged to see the growing interest and receptivity from a broader range of specialties as well. We alluded to an example in dermatology, and we see potential there for continued growth and interactions to really grow this market and move more patients towards treatment.

重要的是，我們真的很高興看到更廣泛的專業領域日益增長的興趣和接受度。我們提到了皮膚科的一個例子，我們看到了持續成長和互動的潛力，可以真正發展這個市場並使更多患者接受治療。

And David, to your question on the design of HARBOR Part 2, our pivotal registrational study, I think as Christy mentioned earlier, over the last many years, we have been really working with the SM overall community on this disease all the way from indolent to advanced and see and explore and all the spectrum of the subtypes of this disease. And we have a good understanding of SM as a disease, not only from subtypes of patients, but what really patients and physicians will be looking for in the next many years. I think all these data and this knowledge is factored in our development. We'll be able to share more in the next weeks and months on these data.

大衛，對於你關於HARBOR 第2 部分（我們的關鍵註冊研究）設計的問題，我認為正如克里斯蒂之前提到的，在過去的許多年裡，我們一直在與SM 整個社區就這種疾病進行真正的合作，從惰性到無痛先進、觀察和探索這種疾病的所有亞型。我們對 SM 作為一種疾病有了很好的了解，不僅來自患者的亞型，而且還來自患者和醫生在未來幾年真正尋求的東西。我認為所有這些數據和知識都是我們發展的因素。我們將在接下來的幾週和幾個月內分享更多有關這些數據的資訊。

Smoldering to your specific question, as we all know, it's a very, very small group of patients, about 2% or 2.5% of the SM. And clearly, dedicated studies for these patients are very difficult to execute. But it is a group of patients that are very interesting that we know very well, including the way we work it. And our data are influencing the changes of definitions of this disease with the expert community.

悶悶不樂地回答你的具體問題，眾所周知，這是一個非常非常小的患者群體，大約佔 SM 的 2% 或 2.5%。顯然，針對這些患者的專門研究非常難以執行。但這是一群非常有趣的患者，我們非常了解，包括我們的工作方式。我們的數據正在影響專家界對這種疾病的定義的變化。

Sudan Loganathan, Stephens.

蘇丹·洛加納森，史蒂芬斯。

Hi. Thank you for squeezing me in, and congrats on the great quarter and taking my questions.

你好。感謝您讓我參與進來，祝賀這個偉大的季度並回答了我的問題。

With the strong long trajectory for AYVAKIT and the market know-how that you have established, do you have any interest in M&A or other business development activities to bolster any late-stage assets that can benefit from the synergies that you have with AYVAKIT's market that you've established? Or is the focus kind of looking towards capital allocations into the in-house pipeline that you're developing with elenestinib and BLU-808 and maybe some other areas that you're interested in?

憑藉 AYVAKIT 強大的長期發展軌跡以及您已建立的市場專業知識，您是否有興趣進行併購或其他業務開發活動來支持任何後期資產，這些資產可以從您與 AYVAKIT 市場的協同效應中受益你已經建立了嗎？還是重點關注您正在使用 elenestinib 和 BLU-808 開發的內部管道以及您感興趣的其他一些領域的資本分配？

Yeah. Thank you, Sudan, for the question. I think we have just the tremendous kind of benefit at Blueprint Medicines to be able to drive our growth organically. And our research team has been over the, since our founding, 13-ish years ago, has had a tremendous productivity in bringing forth innovative new molecules against targets of interest.

是的。謝謝蘇丹提出的問題。我認為 Blueprint Medicines 為我們帶來了巨大的好處，能夠推動我們的有機成長。自 13 年前成立以來，我們的研究團隊一直在針對感興趣的目標開發創新的新分子方面取得了巨大的生產力。

And so our focus and our capital allocation is really on internal programs between AYVAKIT, elenestinib, and BLU-808 has this potential to go very broad. Those are really where we're prioritizing how we think about capital. There's a lot going on in our own labs that we don't talk about with all of you. And so as those progress, we look forward to be able to discuss those.

因此，我們的重點和資本分配實際上是 AYVAKIT、elenestinib 和 BLU-808 之間的內部項目，具有非常廣泛的潛力。這些確實是我們對資本的優先考慮的地方。我們自己的實驗室裡發生了很多事情，我們不會與你們所有人談論。因此，隨著這些進展，我們期待能夠討論這些問題。

We're always out talking to everybody from a BD perspective, and that is to optimize our own portfolio and how we allocate our own dollars and thinking about how we can partner on our programs. And also if there is anything externally, that would make sense. But really, our focus is internally and really driving that operating leverage both based on -- and financial efficiency to continue to bring innovation forward for patients who have significant medical needs.

我們總是從 BD 的角度與每個人交談，那就是優化我們自己的投資組合以及我們如何分配自己的資金，並考慮如何在我們的專案上合作。而且如果有任何外在因素，那就有意義了。但實際上，我們的重點是內部並真正推動基於財務效率的營運槓桿，以繼續為有重大醫療需求的患者帶來創新。

Thank you. That concludes today's Q&A. Ms. Kate Haviland, I turn the call back over to you.

謝謝。今天的問答就到此結束。凱特哈維蘭女士，我將電話轉回給您。

Thank you, everyone, for joining us today.

謝謝大家今天加入我們。

As we come into closing out 2024, really, AYVAKIT's strong revenue ramp, coupled with our disciplined investment and our most compelling product opportunities, as we just talked about with the last question, has put us on a path to drive sustainable growth while we enhance long-term shareholder value. And we're setting up for a very, very exciting 2025 at Blueprint Medicines, and we look forward to, in a few short weeks here, talking more about that when we kick off the year.

事實上，隨著2024 年即將結束，AYVAKIT 強勁的收入成長，加上我們嚴格的投資和最引人注目的產品機會，正如我們剛剛在最後一個問題中談到的那樣，使我們走上了推動可持續成長的道路，同時我們增強了長期股東價值。我們正在為 Blueprint Medicines 迎接一個非常非常激動人心的 2025 年，我們期待在短短幾週內，在新的一年開始時更多地討論這一問題。

So thank you, all, and thank you for your continued support of Blueprint.

謝謝大家，也謝謝你們對 Blueprint 的持續支持。

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。您現在可以斷開連線。