Blueprint Medicines Corp (BPMC) 2023 Q4 法說會逐字稿

Good morning. My name is Drew. I'll be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicines fourth quarter and full year 2023 financial results conference call. (Operator Instructions) Thank you.

早安.我叫德魯。今天我將擔任你們的會議操作員。此時，我歡迎大家參加 Blueprint Medicines 第四季和 2023 年全年財務業績電話會議。（操作員說明）謝謝。

Jenna Cohen, you may begin your conference.

珍娜·科恩，您可以開始會議了。

Thank you, Drew. Good morning, everyone. Welcome to Blueprint Medicines fourth quarter and full year 2023 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 slides that will be reviewing today by going to the Investors section of our website at www.blueprintmedicines.com.

謝謝你，德魯。大家，早安。歡迎參加 Blueprint Medicines 2023 年第四季和全年財務和營運業績電話會議。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，造訪今天將要審查的新聞稿和幻燈片。

Joining me are Kate Haviland, Chief Executive Officer; Philina Lee, Chief Commercial Officer; Fouad Namouni, President, Research & Development; Mike Landsittel, Chief Financial Officer; Christina Ross, Chief Operating Officer; Becker Hewes, Chief Medical Officer, are also on the line and available during Q&A.

與我一起出席的還有執行長凱特哈維蘭 (Kate Haviland)； Philina Lee，首席商務長； Fouad Namouni，研發總裁；麥克‧蘭西特爾 (Mike Landsittel)，財務長；克里斯蒂娜·羅斯，營運長；首席醫療官 Becker Hewes 也在線上並在問答環節中提供幫助。

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 through 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，包括我們向美國證券交易委員會提交的報告中所述的結果，請注意不要過度依賴這些前瞻性陳述，藍圖不承擔任何更新此類陳述的義務。

With that, I'll now hand the call over to Kate.

現在，我將把電話轉給凱特。

Thank you, Jenna, and good morning, everyone. 2023 with a pivotal year for Blueprint Medicines as we successfully brought forward AYVAKIT to become the first and only approved medicine for patients with indolent systemic mastocytosis, or ISM. As we enter 2024 AYVAKIT, it will continue to be the foundation of our thriving business. With our early launch momentum, putting AYVAKIT firmly on the path to becoming a multibillion-dollar product.

謝謝你，珍娜，大家早安。 2023 年對 Blueprint Medicines 來說是關鍵的一年，我們成功推出 AYVAKIT 成為第一個也是唯一一個獲準治療惰性系統性肥大細胞增多症 (ISM) 患者的藥物。隨著我們進入 2024 年 AYVAKIT，它將繼續成為我們業務蓬勃發展的基礎。憑藉我們早期的推出勢頭，AYVAKIT 堅定地走上了成為價值數十億美元產品的道路。

Our growing revenue also enabled us to invest in additional compelling opportunities in our pipeline to drive longer-term growth and deliver even more transformational medicines in the future. To achieve our goals this year, we're focusing on three key aspects of the business.

我們不斷增長的收入也使我們能夠在管道中投資更多引人注目的機會，以推動長期成長並在未來提供更多變革性藥物。為了實現今年的目標，我們將重點放在業務的三個關鍵方面。

Let's start with AYVAKIT's blockbuster potential and its ability to drive durable revenue growth for Blueprint well into the next decade. We know that the first few quarters of launch are critical in dividing the sales trajectory for a product and we have driven a very strong first six months of results in this ISM launch, establishing the foundation for future growth.

讓我們從 AYVAKIT 的巨大潛力及其在未來十年推動 Blueprint 收入持續成長的能力開始。我們知道，發布的前幾季對於劃分產品的銷售軌跡至關重要，並且我們在此次 ISM 發布中推動了非常強勁的前六個月業績，為未來的成長奠定了基礎。

We've clearly demonstrated our ability to reach patients and drive revenue, achieving $204 million in global AYVAKIT revenue in 2023 and 84% increase over 2022. This compelling growth was primarily driven by the uptake in patients with ISM, who comprise about 95% of all patients with SM. A sizable rare disease patient population that we estimate at 70,000 prevalent patients in the US and Europe alone.

我們清楚地展示了我們接觸患者和增加收入的能力，2023 年 AYVAKIT 全球收入達到 2.04 億美元，比 2022 年增長 84%。這種引人注目的成長主要是由 ISM 患者的接受所推動的，這些患者約佔所有 SM 患者的 95%。據我們估計，光在美國和歐洲就有 7 萬名罕見疾病患者。

Today, we are pleased to provide 2024 AYVAKIT revenue guidance of $350 million to $390 million, putting us on pace to nearly double our sales this year. This revenue trajectory is very similar to other notable rare disease product launches, such as Soliris and Jakafi. With additional similarities being a compelling new first in class medicine approved to address a significant medical need in building a new multi-billion dollar market. These similar attributes and importantly similar sales trajectory is why we believe the launch of AYVAKIT is in SM is one of the most exciting rare disease launches happening across the industry today, and we are just now scratching the surface.

今天，我們很高興提供 2024 年 AYVAKIT 收入指導，為 3.5 億至 3.9 億美元，這使我們今年的銷售額有望實現近一倍。這一收入軌跡與其他著名的罕見疾病產品發布非常相似，例如 Soliris 和 Jakafi。其他相似之處是一種引人注目的新型一流藥物，已被批准用於滿足建立新的數十億美元市場的重大醫療需求。這些相似的屬性和重要的是相似的銷售軌跡是為什麼我們相信 AYVAKIT 在 SM 中的推出是當今整個行業最令人興奮的罕見疾病產品之一，而我們現在才剛剛觸及表面。

In 2024, our primary focus is on reaching more patients with SM in the US and also now in Europe with our EMA approval in ISM this past December. AYVAKIT's compelling efficacy and safety profile, coupled with the chronic nature of ISM, meaning that both new patient starts and the cumulative effect of patients staying on therapy for longer durations are important drivers of revenue this year and beyond.

2024 年，我們的主要重點是涵蓋美國和歐洲的更多 SM 患者，去年 12 月我們的 ISM 獲得了 EMA 批准。AYVAKIT 引人注目的療效和安全性，加上 ISM 的長期性質，意味著新患者的開始治療和患者長期接受治療的累積效應都是今年及以後收入的重要驅動力。

I will hand it over to Philina next on the call and she'll go into more detail on AYVAKIT’s performance in Q4 and why we expect our strong and steady growth to continue, as we drive towards peak sales of greater than $2 billion.

我將在接下來的電話會議中將其交給Philina，她將更詳細地介紹AYVAKIT 第四季度的業績，以及為什麼我們預計我們將繼續強勁而穩定的增長，因為我們正朝著超過20 億美元的銷售額高峰邁進。

And yes, we are now pointing you all to a peak opportunity for AYVAKIT that is greater than $2 billion. For the past 12 to 18 months, since before our FDA approval on ISM, we have been citing a peace opportunity for AYVAKIT of greater than $1.5 billion. Now, based on the strong underlying fundamentals that are driving our early sales trajectory and the rapid growth and diagnosis that has led to an expanding SM market, our conviction has grown. The AYVAKIT will be able to achieve peak global sales of greater than $2 billion.

是的，我們現在向大家指出 AYVAKIT 價值超過 20 億美元的巔峰機會。在過去的 12 到 18 個月裡，自從 FDA 批准 ISM 以來，我們一直在為 AYVAKIT 帶來超過 15 億美元的和平機會。現在，基於推動我們早期銷售軌蹟的強勁基本面，以及導致 SM 市場不斷擴大的快速成長和診斷，我們的信念更加堅定。AYVAKIT 將能夠實現超過 20 億美元的全球高峰銷售額。

Now let's turn to our second area of focus, advancing our portfolio targeting allergic inflammatory diseases where mast cells play a central role. Last month, I shared how we are focusing our investment in our most exciting research and development programs with opportunities to address high medical needs in large patient populations, and importantly, in therapeutic areas that play to our strengths by leveraging our expertise and our infrastructure.

現在讓我們轉向我們的第二個重點領域，推進我們針對肥大細胞發揮核心作用的過敏性發炎疾病的產品組合。上個月，我分享了我們如何將投資重點放在最令人興奮的研發項目上，這些項目有機會滿足大量患者群體的高醫療需求，更重要的是，投資於透過利用我們的專業知識和基礎設施發揮我們優勢的治療領域。

A primary area of focus for us this year is to advance our portfolio of approved and investigational programs targeting mast cell mediated diseases. Blueprint is uniquely positioned to drive novel science in this space, because of our scientific leadership and targeting KIT and our proprietary insights into mast cell biology, an important area of science that has been historically underappreciated.

今年我們的主要關注領域是推進針對肥大細胞介導疾病的已批准和研究計畫組合。Blueprint 在推動這一領域的新穎科學方面處於獨特的地位，因為我們的科學領導力和目標KIT 以及我們對肥大細胞生物學的專有見解，肥大細胞生物學是一個歷史上一直被低估的重要科學領域。

With AYVAKIT and Elenestinib, we are fully covering mast cell diseases driven by mutated kit, and this year we are expanding into a much larger opportunity driven by wild-type KIT with BLU-808.

憑藉 AYVAKIT 和 Elenestinib，我們全面涵蓋了由突變試劑盒驅動的肥大細胞疾病，今年我們將透過 BLU-808 擴展到由野生型 KIT 驅動的更大機會。

We are particularly excited about the potential for BLU-808 to impact fundamental biology and a number of large diseases with significant medical need starting the chronic urticaria. We believe this program will move quickly with a higher than typical probability of success at this stage, given our track record of translating our discovery expertise and targeting KIT into clinical impact and now commercial success.

我們對 BLU-808 影響基礎生物學和以慢性蕁麻疹為代表的許多具有重大醫療需求的重大疾病的潛力感到特別興奮。鑑於我們將我們的發現專業知識轉化為 KIT 並將其轉化為臨床影響和現在的商業成功的記錄，我們相信該計劃將在現階段以高於典型成功機率的方式快速推進。

Next week, we'll have a huge presence at the American Academy of Allergy, Asthma and Immunology meetings, often known as AAAAI, which is the largest allergy and immunology conference in the US and taking place in Washington, DC this year. Later on the call, Fouad will go into more depths on what we will be showcasing at AAAAI, as well as provide an update on our development stage portfolio.

下週，我們將大量出席美國過敏、氣喘和免疫學會會議（通常稱為 AAAAI），這是美國最大的過敏和免疫學會議，今年在華盛頓特區舉行。稍後在電話會議上，Fouad 將更深入地介紹我們將在 AAAAI 上展示的內容，並提供我們開發階段產品組合的最新資訊。

The third area of focus for us is maintaining a strong and durable financial position. Cash management will continue to be a priority area for us to focus on in 2024. And as we sit here today, we see a clear path to profitability through the combination of strong revenue ramp and disciplined operating expenses, which will result in significant decrease in operating cash burn in 2024 and beyond.

我們關注的第三個領域是維持強大且持久的財務狀況。現金管理仍將是我們2024年重點關注的領域。當我們今天坐在這裡時，我們看到了透過強勁的收入成長和嚴格的營運支出相結合來實現盈利的清晰途徑，這將導致 2024 年及以後的營運現金消耗大幅減少。

Mike will talk more about our financial results and our approach to balancing disciplined capital allocation and investing at the same time in our compelling near and long-term growth opportunities.

麥克將更多地談論我們的財務表現以及我們平衡嚴格的資本配置和同時投資於我們引人注目的近期和長期成長機會的方法。

Business development will also continue to be core to how we build and optimize our business in a sustainable way. To that end, I'm very pleased to say that we have made significant progress on a deal that will enable GAVRETO to continue to be commercially available to patients in the US, while minimizing the financial impact to Blueprint. We look forward to updating you in the near future once that deal is finalized.

業務發展也將繼續成為我們以永續方式建立和優化業務的核心。為此，我很高興地說，我們在一項交易上取得了重大進展，該交易將使 GAVRETO 能夠繼續向美國患者商業化銷售，同時最大限度地減少對 Blueprint 的財務影響。一旦交易敲定，我們期待在不久的將來向您通報最新情況。

Now, I'll hand it over to Philina, who will go into more detail in our commercial performance. Philina?

現在，我將把它交給菲莉娜，她將在我們的商業表演中詳細介紹。菲莉娜？

Thanks, Kate. AYVAKIT achieved $204.2 million in net product revenues in 2023, representing 84% revenue growth over last year. Fourth quarter, revenues grew 30% quarter on quarter to $71 million with $63.6 million in the US. This growth was driven by several key factors. New patient starts a decline in our share of free goods, low discontinuation rates and high compliance. ISM is the clear growth driver with the majority of new starts at the 25 mg dose.

謝謝，凱特。AYVAKIT 2023 年產品淨收入達 2.042 億美元，較去年成長 84%。第四季度，營收季增 30%，達到 7,100 萬美元，其中美國營收為 6,360 萬美元。這一增長是由幾個關鍵因素推動的。新患者開始減少我們的免費商品份額、低停藥率和高依從性。ISM 是明顯的成長動力，大多數新產品的劑量為 25 毫克。

Starting with patients on therapy. We hit a major milestone in January with approximately 1000 patients on AYVAKIT in the US. We were looking to see if this would come in December or January, and we're encouraged by the strong demand we see coming into Q1. We are thrilled to hit this thousand patient milestone this early in the launch, and we are focused on driving continued growth.

從接受治療的患者開始。我們在一月達到了一個重要的里程碑，在美國 AYVAKIT 上有大約 1000 名患者。我們想看看這是否會在 12 月或 1 月發生，我們對第一季的強勁需求感到鼓舞。我們很高興在推出之初就達到了千名患者的里程碑，我們致力於推動持續成長。

Today, we're setting revenue guidance that reflects the strong and steady continued growth we expect in 2024. As we get closer to realizing AYVAKIT's blockbuster potential. Our guidance range of $360 million to $390 million, assumed another year of more than 80% year over year revenue growth at the midpoint.

今天，我們制定的收入指引反映了我們預計 2024 年強勁、穩定的持續成長。隨著我們越來越接近實現 AYVAKIT 的巨大潛力。我們的指引範圍為 3.6 億至 3.9 億美元，假設中點營收年增率又超過 80%。

We have good insight into the fundamentals driving our revenue, namely new patient starts, compliance, duration, free goods, and our international performance. This range reflects the inherent variability in those fundamentals. With guidance now in place, we're going to move away from providing a quarterly patient on therapy number. We will continue to share commentary on how the launch is progressing.

我們對推動我們收入的基本面有深入的了解，即新患者開始、合規性、持續時間、免費商品和我們的國際業績。這個範圍反映了這些基本面的固有變化。有了現在的指導，我們將不再按季度提供一次患者的治療號碼。我們將繼續分享有關發布進度的評論。

Looking next at persistence, we expected strong persistence in ISM based on AYVAKIT’s clinical profile and the chronic nature of the disease. And even though it's early days, all signs point to extended durations of therapy with low discontinuation rates and high compliance launch to date.

接下來看看持久性，根據 AYVAKIT 的臨床特徵和疾病的慢性性質，我們預期 ISM 具有很強的持久性。儘管現在還處於早期階段，但所有跡像都表明治療持續時間較長，停藥率較低，迄今為止啟動的依從性較高。

It has been a surprise upside is how quickly we've moved the needle on our free goods share dropping to approximately 25%, as we grow the number of ISM patients on therapy. We have just reported our second strong quarter of revenue from our ISM launch. Let me tell you why we expect to sustain this growth in 2024 and beyond. Our commercial strategy is grounded in strong continued execution across multiple paths that will drive sustained growth in this market.

令人驚訝的好處是，隨著接受治療的 ISM 患者數量的增加，我們的免費商品份額下降到了大約 25%，速度如此之快。我們剛剛報告了 ISM 推出帶來的第二個強勁收入季度。讓我告訴您為什麼我們預計在 2024 年及以後保持這種增長。我們的商業策略基於多條路徑的強有力的持續執行，這將推動該市場的持續成長。

First, we're ramping up our direct to patient marketing to further drive awareness and activate patients to seek treatment. The SM market is growing and we've only captured a small fraction of it so far. Today, there are more than 20,000 diagnosed patients in the US alone and about half are not well controlled on symptom directed therapies. We know this is a chronic market where patient preference is sticky. Once patients start AYVAKIT that positive clinical experience bodes well for chronic duration of therapy.

首先，我們正在加強對患者的直接行銷，以進一步提高意識並鼓勵患者尋求治療。SM 市場正在成長，但到目前為止我們只佔據了其中的一小部分。如今，光在美國就有超過 2 萬名確診患者，其中約一半患者在症狀導向治療中病情未得到良好控制。我們知道這是一個長期市場，患者的偏好具有黏性。一旦患者開始使用 AYVAKIT，積極的臨床經驗預示著長期治療的良好前景。

Second, we're expanding AYVAKIT's prescriber base across all specialties and settings, and we're nowhere near saturation. We are seeing strong receptivity to AYVAKIT's profile among both hem/oncs and allergists in the academic and community settings. Breadth of prescribing is happening exactly where we want as we're motivating more allergists to prescribe AYVAKIT, and we're adding more prescribers at the top of the concentration curve.

其次，我們正在擴大 AYVAKIT 的所有專業和環境的處方者基礎，而且我們還遠遠沒有達到飽和。我們看到學術界和社區環境中的 hem/oncs 和過敏症專家對 AYVAKIT 的形像有很強的接受度。處方的廣度正在按照我們想要的方式進行，因為我們正在激勵更多的過敏症專家開出 AYVAKIT 處方，並且我們在濃度曲線的頂部添加了更多的處方者。

You can see this in the chart on the left, which shows early AYVAKIT adoption among the top 400 SM providers who see about 4,300 unique SM patients. We continue to grow the breadth of prescribing here in light green, and we're also beginning to see depth of prescribing with providers who have already started two, three or more patients on therapy in darker green.

您可以在左側的圖表中看到這一點，該圖表顯示了 400 家頂級 SM 提供者的早期採用 AYVAKIT，他們接待了大約 4,300 名獨特的 SM 患者。我們繼續擴大淺綠色處方的廣度，並且我們也開始看到已經開始對兩個、三個或更多患者進行深綠色治療的提供者的處方深度。

As we expected the first positive experience is leading providers to recommend AYVAKIT to the next patients who are coming in for their scheduled appointments. Breadth of prescribing is an important lead indicator for long-term growth. We are highly encouraged to see prescriber breadth and early signs of prescriber depth at this point in launch. Over time, we expect to see the cumulative impact of growing this motivated prescriber base together with activating more patients to seek what's possible with AYVAKIT.

正如我們預期的那樣，第一個積極的體驗是引導提供者向下一個前來預約的患者推薦 AYVAKIT。處方的廣度是長期成長的重要先行指標。我們非常高興地看到處方者的廣度和處方者深度的早期跡象。隨著時間的推移，我們預計會看到擴大這種積極的處方者基礎以及激勵更多患者尋求 AYVAKIT 的可能性所產生的累積影響。

That's why I'm so confident about our ability to both grow and capture this market. We understand the SM market better than anyone else. What activates patients to move away from the symptom directed polypharmacy, they're habituated to and try therapy designed to address the underlying driver of disease, what drives providers urgency to treat, what influences their prescribing behavior and how to ensure that access is seamless for patients and providers. We are making great headway to disrupt entrenched attitudes and behaviors about disease control and treatment and to drive patients and providers to take action.

這就是為什麼我對我們發展和佔領這個市場的能力充滿信心。我們比任何人都更了解SM市場。是什麼促使患者放棄以症狀為導向的多重用藥，他們習慣並嘗試旨在解決疾病潛在驅動因素的治療，是什麼促使提供者迫切需要治療，什麼影響他們的處方行為，以及如何確保無縫獲取患者和提供者。我們正在取得巨大進展，以打破有關疾病控制和治療的根深蒂固的態度和行為，並推動患者和醫療服務提供者採取行動。

With two quarters of strong performance and our guidance today, we are in the early innings of a pioneering rare disease launch. We are exactly where we thought we would be and we're delivering what we’ve said we would deliver. As we've seen from the launch trajectory of other rare disease blockbusters, we are right on track to capture AYVAKIT peak opportunity of over $2 billion.

憑藉兩個季度的強勁表現和我們今天的指導，我們正處於開創性罕見疾病推出的早期階段。我們正處於我們所設想的位置，並且我們正在兌現我們所說的我們將兌現的承諾。正如我們從其他罕見疾病大片的上市軌跡中看到的那樣，我們正朝著抓住 AYVAKIT 超過 20 億美元的峰值機會的方向前進。

With that, I'll hand it to Fouad to share what you can expect from Blueprint Medicines at AAAAI.

接下來，我將把它交給 Fouad，分享您對 AAAAI 的 Blueprint Medicines 的期望。

Thank you, Philina. With more than 10 years of experience in systemic mastocytosis, we have built an extensive repository of knowledge to uncover insights into SM disease biology, our patient's journey, our prescriber management of the disease spectrum from ISM to ASM.

謝謝你，菲莉娜。憑藉在系統性肥大細胞增多症方面 10 多年的經驗，我們建立了廣泛的知識庫，以揭示對 SM 疾病生物學、患者旅程、從 ISM 到 ASM 疾病譜的處方者管理的見解。

At Blueprint Medicines, we are redefining how SM is treated across a broad network of academic leaders and prescribers with whom we are not only expanding the frontiers of innovation in SM, but also in many other mast cell driven diseases.

在 Blueprint Medicines，我們正在廣泛的學術領袖和處方者網絡中重新定義 SM 的治療方式，我們不僅擴大了 SM 的創新前沿，而且還擴大了許多其他肥大細胞驅動疾病的創新前沿。

With two oral presentations and seven posters, Blueprint will lead SM Science and Medicine at the 2024 AAAAI Conference. The long-term efficacy and safety data from Pioneer will continue to establish AYVAKIT as the standard of care and the only available option to treat the root cause of systemic mastocytosis. Additional data will include health outcomes measures and reduction in polypharmacy.

Blueprint 將透過兩次口頭報告和七張海報在 2024 年 AAAAI 會議上引領 SM 科學與醫學。Pioneer 的長期療效和安全性數據將繼續將 AYVAKIT 確立為護理標準和治療系統性肥大細胞增多症根本原因的唯一可用選擇。其他數據將包括健康結果測量和複方用藥的減少。

Turning now to our pipeline. The extensive data we generated from Pioneer and from real world evidence in SM coupled with the regulatory experience we gained it with AYVAKIT development are enabling us to build a robust differentiated development path for Elenestinib, our next generation D816V mutated KIT inhibitor.

現在轉向我們的管道。我們從 Pioneer 和 SM 的真實世界證據中產生的大量數據，加上我們在 AYVAKIT 開發中獲得的監管經驗，使我們能夠為下一代 D816V 突變 KIT 抑製劑 Elenestinib 建立強大的差異化開發路徑。

We very recently presented data showing an AYVAKIT inhibitor driver clinically meaningful symptom improvement across those levels with well-tolerated safety profile. We see a lot of potential with Elenestinib as a core part of expanding our SM franchise.

我們最近提供的數據顯示，AYVAKIT 抑制劑可在這些層面上推動臨床上有意義的症狀改善，並具有良好的耐受性安全性。我們看到 Elenestinib 作為擴大 SM 特許經營權的核心部分的巨大潛力。

Mast cells are well-established key drivers for many allergic and inflammatory diseases, where there is still a high medical need. However, their role as therapeutic targets for inflammation has often been underappreciated in our industry. At Blueprint Medicines, we are building on our expertise in mast cell biology to identify targets and develop therapies for variety of mast cell driven inflammatory diseases.

肥大細胞是許多過敏和發炎疾病的公認關鍵驅動因素，這些疾病仍然有很高的醫療需求。然而，它們作為發炎治療標靶的作用在我們的行業中常常被低估。在 Blueprint Medicines，我們正在利用肥大細胞生物學的專業知識來確定標靶並開發針對各種肥大細胞驅動的發炎性疾病的療法。

Last month, we presented for the first time more detail on the preclinical profile of BLU-808. A profile that met or exceeded all our key criteria. It is potent on wild-type kit, highly selective and it has drug properties compatible with once daily oral administration.

上個月，我們首次介紹了 BLU-808 臨床前概況的更多細節。符合或超過我們所有關鍵標準的個人資料。它對野生型試劑盒有效，選擇性高，並且具有與每日一次口服給藥相容的藥物特性。

Next week, we'll also share compelling in vivo activity of BLU-808 in models of mast cell activation and asthma that support our development strategy into the diseases and beyond. We are on track to submit an IND in the second quarter of this year, and then we will initiate the [SAB/MAB]study.

下週，我們還將分享 BLU-808 在肥大細胞活化和氣喘模型中令人信服的體內活性，這些活性支持我們針對疾病及其他疾病的開發策略。我們預計在今年第二季提交 IND，然後我們將啟動 [SAB/MAB] 研究。

Finally, on the solid tumor part of our pipeline, we are advancing our CDK2 inhibitor BLU-222 one of the most exciting programs that we have in clinical development. BLU-222 is an important value driver for Blueprint Medicine and one that we are looking to move forward in the context of a partnership.

最後，在我們管道的實體腫瘤部分，我們正在推進我們的 CDK2 抑制劑 BLU-222，這是我們臨床開發中最令人興奮的項目之一。BLU-222 是 Blueprint Medicine 的重要價值驅動因素，我們希望在合作關係的背景下向前邁進。

CDK2 is a clinically validated cell target with the potential to impact a large patient population with HER1 positive, HER2 negative breast cancer. BLU-222 has a very encouraging profile with a broad therapeutic window and best in class selectivity. Our goal is to pursue it in combination with approved CDK4/6 medicines to prolong breast cancer patient survival. We have had significant engagement on this program with the range of potential partners and those conversations continue very productively.

CDK2 是一種經過臨床驗證的細胞標靶，有可能影響大量 HER1 陽性、HER2 陰性乳癌患者群體。BLU-222 具有非常令人鼓舞的特點，具有廣泛的治療窗口和一流的選擇性。我們的目標是將其與已批准的 CDK4/6 藥物結合，以延長乳癌患者的生存期。我們與眾多潛在合作夥伴就該計劃進行了深入的接觸，並且這些對話繼續非常富有成效。

With that, I will turn a call over to Mike to review our financial updates.

這樣，我將打電話給麥克，以查看我們的財務最新情況。

Thanks, Fouad. Earlier this morning, we reported detailed financial results in our press release. For today's call, I'll touch on a few highlights.

謝謝，福阿德。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，我將談幾個要點。

For the full year, total revenues were $249.4 million, including $204.2 million in net product revenues from sales of AYVAKIT and $45.2 million in collaboration and license revenues. Of these full year revenues, [$71 billion] of AYVAKIT net product revenues were recorded in the fourth quarter.

全年總收入為 2.494 億美元，其中包括 AYVAKIT 銷售帶來的 2.042 億美元產品淨收入以及 4,520 萬美元的合作和授權收入。在這些全年收入中，AYVAKIT 產品淨收入 [710 億美元] 記錄於第四季。

In 2024, we anticipate that we will achieve $360 million to $390 million in AYVAKIT net product revenues. We expect that the ex-US AYVAKIT revenue split in 2024 will be approximately consistent with what we observed in 2023, as we launch first in Germany before expanding to other countries as pricing and reimbursement is negotiated.

到 2024 年，我們預計 AYVAKIT 產品淨收入將達到 3.6 億至 3.9 億美元。我們預計 2024 年除美國以外的 AYVAKIT 收入分配將與我們在 2023 年觀察到的情況大致一致，因為我們首先在德國推出，然後在協商定價和報銷後擴展到其他國家。

Today's guidance illustrates we are on the path to capturing AYVAKIT's peak opportunity of $2 billion. This revenue growth coupled with expense, discipline and focused investment is what is accelerating our path to profitability.

今天的指引顯示我們正在抓住 AYVAKIT 20 億美元的巔峰機會。這種收入成長加上費用、紀律和集中投資正在加速我們的獲利之路。

We do not anticipate any material collaboration revenue from existing collaborations in 2024. We are nearing a path forward for GAVRETO in the US and plan to provide an update next week to coincide with a termination date for our existing agreement with Roche. We continue to expect that the wind down of the Roche collaboration for GAVRETO will result in significantly lower year over year operating expenses related to GAVRETO and will have no material impact to our overall expense plans in 2024.

我們預期 2024 年現有合作不會產生任何實質合作收入。我們正在接近 GAVRETO 在美國的發展道路，並計劃在下週提供最新信息，以配合我們與羅氏現有協議的終止日期。我們仍然預計，羅氏與加夫雷托 (GAVRETO) 合作的結束將導致與加夫雷托 (GAVRETO) 相關的營運費用同比大幅下降，並且不會對我們 2024 年的總體費用計劃產生重大影響。

Our total costs and operating expenses continue to decline and were $735.7 million for the full year and $177.1 million for the fourth quarter. We anticipate our R&D expenses will continue to decline in 2024, as we wind down our early stage EGFR clinical programs partially offset by increased investments in our programs for mast cell mediated diseases, specifically BLU-808. We expect only a small increase in SG&A expense as we gain operating leverage from our commercial infrastructure and continue to drive significant increases in revenues.

我們的總成本和營運費用持續下降，全年為 7.357 億美元，第四季為 1.771 億美元。我們預計我們的研發費用將在 2024 年繼續下降，因為我們逐漸結束了早期 EGFR 臨床項目，部分抵消了對肥大細胞介導疾病項目（特別是 BLU-808）的投資增加。隨著我們從商業基礎設施中獲得營運槓桿並繼續推動收入大幅成長，我們預計 SG&A 費用只會小幅增加。

Last month, Kate shared our vision for maintaining financial strength at Blueprint. We have a focused spending plan that allows for continued reduction in operating expenses, while also investing in opportunities for longer term growth. We have prioritized capital allocation towards a portfolio built around mast cell mediated diseases, solid tumors implicated by cycling dependent kinase biology and ongoing early research efforts, as we believe that these areas provide the best opportunity to drive long-term value.

上個月，Kate 分享了我們保持 Blueprint 財務實力的願景。我們有一個有針對性的支出計劃，可以持續減少營運支出，同時也投資於長期成長的機會。我們優先將資本配置到圍繞肥大細胞介導的疾病、循環依賴性激酶生物學涉及的實體瘤以及正在進行的早期研究工作構建的投資組合，因為我們相信這些領域提供了推動長期價值的最佳機會。

Entering 2024, we are in an exceptionally strong and durable financial position with $767.2 million in cash. We are commercializing AYVAKIT globally a first and best-in-class medicine that is growing revenues on the way to blockbuster status. We expect our operating cash burn to further decline in 2024, even as we advance our portfolio of high potential medicines like BLU-808. Our pathway to profitability is becoming clearer, solidifying our financial profile and our ability to generate long-term value.

進入 2024 年，我們的財務狀況異常強勁且持久，擁有 7.672 億美元現金。我們正在全球範圍內將 AYVAKIT 商業化，這是一種一流的藥物，該藥物正在不斷增加收入，邁向重磅炸彈的地位。我們預計，即使我們推進 BLU-808 等高潛力藥物組合，我們的營運現金消耗也會在 2024 年進一步下降。我們的獲利之路變得更加清晰，鞏固了我們的財務狀況和創造長期價值的能力。

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

這樣，如果有任何問題，我現在會將電話轉回接線生。操作員？

(Operator Instructions) Brad Canino, Stifel.

（操作員說明）Brad Canino，Stifel。

Good morning and Congrats on the quarter. It would be great to hear a description of how the team viewed its overall approach coming into guidance here, and then what you believe this guide now represents about the opportunity? And then I've got a follow up.

早上好，恭喜本季。很高興聽到團隊如何看待這裡的整體方法的描述，然後您認為本指南現在代表了哪些機會？然後我有後續行動。

Thank you, Brad very much. We really appreciate that. Chris, you want to take the question on guidance?

非常感謝你，布拉德。我們真的很感激。克里斯，你想回答有關指導的問題嗎？

Sure, Brad. So as Kate said, you know, we now have two full quarters of experience under our belts with AYVAKIT, and those two quarters have set an incredibly strong foundation for the trajectory that we see for this product. We also have a sense now based on those two quarters of what some of the key drivers are of revenue performance and Philina walked through those. Things like new patient starts, duration of therapy, which increasingly in a chronic market like this is becoming a very important driver of revenue growth as we have a strong and growing base of patients on therapy. And then factors like compliance et cetera, free drug rates.

當然，布拉德。正如 Kate 所說，您知道，我們現在在 AYVAKIT 方面擁有兩個完整季度的經驗，這兩個季度為我們看到的該產品的發展軌跡奠定了極其堅實的基礎。現在，我們也根據這兩個季度對營收表現的一些關鍵驅動因素有了一定的了解，菲利娜也詳細介紹了這些因素。新患者開始治療、治療持續時間等因素在這樣的長期市場中日益成為收入增長的一個非常重要的驅動因素，因為我們擁有強大且不斷增長的接受治療的患者基礎。然後是依從性等因素，免費藥物率。

And so as we've understood those variables and we understand what reasonable ranges are around those variables that's really informed our guide, which like other external milestones, et cetera, that we communicate, we're really putting out so that we can help everyone understand what we think is a reasonable expectation for revenue this year.

因此，當我們了解了這些變量，並且了解了這些變量的合理範圍時，這些變量真正為我們的指南提供了信息，就像我們溝通的其他外部里程碑等一樣，我們確實正在推出，以便我們可以幫助每個人都了解我們認為今年收入的合理預期。

One important factor is that we are not even 12 months into this launch. And so one of the things that we're understanding as we go through are some of the quarter on quarter dynamics and how those things will play in. Philina talked about, for example, seasonality in Q4. We know that Q1 is often a quarter, in many and pharma generally where you see impacts around compliance versus that et cetera. So we're understanding how those factors will also play in as we think about the quarter on quarter ramp through the year.

一個重要因素是，我們推出這款產品不到 12 個月。因此，我們在經歷過程中正在了解的一件事是一些季度動態以及這些事情將如何發揮作用。例如，菲利娜談到了第四季的季節性。我們知道，第一季通常是一個季度，在許多製藥行業，通常您會看到合規性與其他方面的影響。因此，當我們考慮全年逐季度的成長時，我們正在了解這些因素將如何發揮作用。

I think the important thing as we pull back is that this guide represents more than 80% year on year growth, again for AYVAKIT. And it is very, very clear if you look at the revenue trajectory that we are on, that we are very much marching down that road towards a $2 billion peak. The trajectory is very much aligned with what we've seen with other compelling rare disease launches. And so, we feel like we're in incredibly strong place and very much demonstrating with each quarter the opportunity that we've been saying is there in SM.

我認為，我們撤回的重要一點是，本指南代表了超過 80% 的同比增長，同樣是 AYVAKIT 的增長。如果你看看我們目前的收入軌跡，就會非常非常清楚地發現，我們正在沿著這條路邁向 20 億美元的頂峰。這一軌跡與我們在其他引人注目的罕見疾病上市中看到的情況非常一致。因此，我們覺得我們處於令人難以置信的強勢地位，並且每個季度都在展示我們一直在說的 SM 中存在的機會。

Great. And then I want to ask on Slide 7, which was a very helpful visualization of the proportion of practices where only one or two patients have started AYVAKIT,. But what were the key execution steps that got that disclosed minority of activated accounts to 3 to 10 patients? And how are you going to replicate that in the remaining, majority that are at 1 to 2?

偉大的。然後我想問幻燈片 7，這是一個非常有用的視覺化，顯示了只有一兩個患者開始 AYVAKIT 的實踐比例。但是，向 3 到 10 名患者揭露少數啟動帳戶的關鍵執行步驟是什麼？你將如何在剩下的大多數 1 到 2 的情況下複製這一點？

Thanks, Brad. Philina, do you want to talk more about that dynamic?

謝謝，布拉德。Philina，你想多談談這種動態嗎？

Thanks for the question Brad. We're really encouraged this early in the launch to see both strong signs of growing prescriber breadths across all specialties and settings. So [hemoc], [AI] and an even split across academic and community, that therein represents how well that real world experience with AYVAKIT's strong profile is playing out and the receptivity. To the point of what's leading providers with their first experience to put on two or more patients, it's really as simple as they start AYVAKIT and can see that positive benefit. It brings it to life in these providers of what's possible with patients. And that is leading to further repeat prescribing and deepening in these accounts.

謝謝布拉德的提問。我們在推出之初就看到了所有專業和環境中處方醫生廣度不斷增長的強烈跡象，對此我們感到非常鼓舞。因此，[hemoc]、[AI] 以及學術界和社區之間的均勻分佈，這代表了 AYVAKIT 強大形象的現實世界經驗的發揮效果以及接受度。對於首次為兩名或更多患者提供治療經驗的領先醫療服務提供者來說，這真的很簡單，只要他們開始使用 AYVAKIT 就可以看到積極的益處。它讓這些提供者為患者帶來了可能的生活。這導致這些帳戶的進一步重複和深化。

From an executional standpoint, I would highlight the efforts of our team that have the greatest amount of promotional focus on the providers who are seeing the greatest number of SM patients. And it's really the strength of both our data analytics that inform that targeting as well as the strong relationships that our team has forged with these top volume prescribers on the ground.

從執行的角度來看，我要強調我們團隊所做的努力，他們將最大程度的促銷重點放在了接待最多 SM 患者的醫療服務提供者身上。這確實是我們的數據分析的優勢，可以告知目標，以及我們的團隊與這些頂級處方醫生建立的牢固關係。

Thanks and congrats again.

再次感謝並恭喜。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Good morning and thanks for taking my question. Here two on the pipeline, for BLU-263 following positive data from the part one portion of the Phase 2/3 trial and ISM, the next key event is in the part two trial. How will you demonstrate the differentiation of this asset relative to AYVAKIT in that portion? And then separately on the CDK2 program, we are going to see data in the first half. Just walk us through your expectations, what you present and the benchmarks here for success and differentiation versus the other CDK2 inhibitors. Thank you.

早安，感謝您提出我的問題。這裡有兩個正在醞釀中，對於 BLU-263，繼 2/3 期試驗第一部分和 ISM 的積極數據之後，下一個關鍵事件是在第二部分試驗中。您將如何展示該資產相對於 AYVAKIT 在那部分的差異？然後單獨在 CDK2 程式上，我們將看到上半年的數據。請向我們介紹您的期望、您提出的內容以及與其他 CDK2 抑制劑相比的成功和差異化基準。謝謝。

Yeah, thank you for the question, Salveen. I'll hand it over to Fouad but we look at our Elenestinib as being a really core part of how we're going to maximize the long-term performance of our overall SM franchise. And as we said before, AYVAKIT set the very, very high bar. I'll hit over to Fouad to talk about how we're going to be able to bring elements important in an innovative way.

是的，謝謝你的提問，薩爾文。我會將其交給 Fouad，但我們將 Elenestinib 視為我們如何最大限度地提高整個 SM 特許經營權的長期績效的真正核心部分。正如我們之前所說，AYVAKIT 設定了非常非常高的標準。我將聯繫福阿德，討論我們如何以創新的方式引入重要的元素。

We presented at ASH a few weeks ago, very robust data on the activity in terms of improving the symptoms with the validated PSS tool for the Elenestinib in patients with indolent systemic mastocytosis. We also show very good safety and tolerability profile. So the Phase 2 POC is very solid there. We are and we continue to gain scientific information from Pioneer. We show some of it at this upcoming AAAAI meeting. We have information from real world evidence. We also gained a very robust experience from a regulatory perspective, not only in the United States, but also in Europe and elsewhere.

幾週前，我們在 ASH 上展示了非常可靠的數據，顯示 Elenestinib 經驗證的 PSS 工具在改善惰性系統性肥大細胞增多症患者症狀方面的活性。我們也表現出非常好的安全性和耐受性。所以第二階段的 POC 非常可靠。我們正在並將繼續從先鋒公司獲得科學資訊。我們將在即將舉行的 AAAAI 會議上展示其中的一些內容。我們有來自現實世界證據的資訊。從監管角度來看，我們也獲得了非常豐富的經驗，不僅在美國，而且在歐洲和其他地方。

All these items are being put together to really put together a differentiated strategy to develop an Elenestinib for what we believe ISM patients will be in a few years from now, not what they were back in 2016, 2017. And think you will see this, reflected in our development strategy as we start the registrational trials.

所有這些項目正在整合在一起，真正制定出差異化策略，為我們認為幾年後 ISM 患者的情況開發 Elenestinib，而不是 2016 年、2017 年的情況。我想您會在我們開始註冊試驗時看到這一點，這反映在我們的發展策略中。

For the CDK-2 question and I think we're happy that the study is continuing the dose escalation in the Phase 1. We're mostly focused on the combination, as I mentioned in my prepared notes on the combination with CDK4/6 medicines. We would be presenting the early safety data from the combination of ribociclib and BLU-222, all with the characteristic and the profile of this combination together. The goal there is really to show that as we go to hormone positive, HER2 and negative breast cancer, the goal is to show that we can combine safely and that safe combination will drive the efficacy in the short and the long-term. Stay tuned for data coming from the VELA study.

對於 CDK-2 問題，我認為我們很高興研究在第一階段繼續劑量遞增。我們主要關注聯合用藥，正如我在準備的關於與 CDK4/6 藥物聯合用藥的筆記中提到的那樣。我們將展示 ribociclib 和 BLU-222 組合的早期安全數據，以及該組合的特徵和概況。我們的目標實際上是要表明，當我們研究荷爾蒙陽性、HER2 和陰性乳癌時，我們可以安全地聯合治療，並且安全的聯合治療將提高短期和長期的療效。請繼續關注 VELA 研究的數據。

Thank you.

謝謝。

Marc Frahm, TD Cowen.

馬克·弗拉姆，TD·考恩。

Yes, thanks for taking my questions and congrats on all the growth in the quarter. Maybe going to that slide of the patient per prescriber, can you maybe give a sense of kind what's the opportunity from the breadth side right? Just deepening at those existing kind 400 treaters versus the depth of -- sorry, the depth of that but then what's the opportunity more at expanding out to many more prescribers and kind of related to that guidance, implies yet the midpoint maybe like a 125, 150 patients per quarter kind of being added to the franchise versus the recent trends been more like 200. I guess maybe can you kind of square those?

是的，感謝您回答我的問題，並祝賀本季的所有成長。也許轉到每個處方者的患者幻燈片，您能否從廣度方面給出一種機會是什麼？只是加深現有的 400 名治療師與深度 - 抱歉，深度，但是擴展到更多處方者以及與該指導相關的機會更多，意味著中點可能像 125，每季度增加150 名患者，而最近的趨勢是增加200 名患者。我想也許你能把這些平方嗎？

Yeah, thanks Marc. I'm going to hit over Philina. I also just wanted to reiterate from the point that Christy made about the guidance. We are 6 months into a launch, we have not had an opportunity to see a full year of ISM revenue and we're continuing to get a sense of some of the seasonal dynamics. And we're incredibly excited that this guidance puts us on the trend line for kind of comparable rare disease products that have just created really compelling markets. Philina, you want to talk about some of the specifics?

是的，謝謝馬克。我要打敗菲莉娜。我也想重申克里斯蒂提出的指導觀點。我們已經推出 6 個月了，我們還沒有機會看到全年的 ISM 收入，我們正在繼續了解一些季節性動態。我們非常興奮的是，這項指導使我們走上了類似罕見疾病產品的趨勢線，這些產品剛剛創造了一個真正引人注目的市場。Philina，你想談一些具體細節嗎？

Yeah, hi Marc. To your question about sort of the opportunity that this represents, when we look at the top 400 treaters by SM patient volume, collectively they are seeing about 4,300 already diagnosed SM patients today. There's substantial headroom to grow both in breadth as well as depth just within these top 400. When we look at the penetration, only about 20% of these top 400 have yet prescribed AYVAKIT, and we see this growing steadily in that sort of light green curve on the top.

是的，嗨馬克。對於您關於這代表的機會的問題，當我們按 SM 患者數量查看排名前 400 的治療師時，他們今天總共治療了約 4,300 名已確診的 SM 患者。在這 400 強中，無論是廣度或深度都有很大的成長空間。當我們觀察滲透率時，這 400 名患者中只有大約 20% 尚未服用 AYVAKIT，我們看到這一比例在頂部的淺綠色曲線中穩步增長。

You also see that substantial opportunity for deepening, and we sort of talked about how the first positive experience leads to repeat prescribing and that's both recognition of the clinical benefit, which is leading providers to think of AYVAKIT for a broader range of their patients.

您還看到了深化的巨大機會，我們談到了第一次積極的經歷如何導致重複處方，這都是對臨床益處的認可，這導致提供者考慮將 AYVAKIT 用於更廣泛的患者。

They typically start with a more severe symptomatic type of patient and they are broadening that lens over time. It's also exciting to see the growth in allergy penetration within and beyond this segment as they become familiar with AYVAKIT, accustomed to the access process. And then again, are sort of phishing and identifying those next patients as they're coming in for treatment.

他們通常從症狀更嚴重的患者開始，隨著時間的推移，他們會擴大視野。令人興奮的是，隨著他們逐漸熟悉 AYVAKIT、習慣了獲取流程，該細分市場內外的過敏滲透率不斷增長。然後，又是一種網路釣魚，並在下一批患者前來接受治療時識別他們。

I think the take home there is, we see significant potential for growth as this continues to accumulate over time both breadth and depth.

我認為，我們看到了巨大的成長潛力，隨著時間的推移，這種成長的廣度和深度都在不斷累積。

To the second part of your question -- pardon me. This is not a sort of 125 to 150 per quarter story alone. I think that the limitations of patients on therapy at the end of every quarter just -- it doesn't tell you when those new patients starts are happening what the duration of therapy is for these patients. We've highlighted how much more important duration will be as a contributor going forward in this launch.

對於你問題的第二部分——請原諒。這不僅僅是每季 125 到 150 個故事。我認為患者在每個季度末接受治療的局限性只是 - 它並沒有告訴你這些新患者何時開始發生這些患者的治療持續時間是多少。我們強調了作為本次發布的貢獻者，持續時間將變得更加重要。

It's a rare disease, we're early, there's variability month over month as Kate alluded to. We're learning those quarterly dynamics. I think a better lens to take is probably that moving average, as well as a breadth of factors that are contributing to that revenue guidance that Christy just highlighted, I think taken together, we're really pleased with the first two quarters. And when we look at the other blockbuster opportunity comparators that Kate mentioned, like we're well within the pack of the trajectory that they've been on towards realizing that blockbuster opportunity for AYVAKIT.

這是一種罕見的疾病，我們還很早，正如凱特所提到的那樣，每個月都有變化。我們正在了解這些季度動態。我認為更好的視角可能是移動平均線，以及有助於克里斯蒂剛才強調的收入指引的廣泛因素，我認為綜合起來，我們對前兩個季度感到非常滿意。當我們看到凱特提到的其他重磅機會比較器時，我們完全處於他們為 AYVAKIT 實現重磅機會的軌跡中。

Okay. Thank you.

好的。謝謝。

Reni Benjamin, Citizens, JMP.

雷尼·本傑明，公民，JMP。

Hey, good morning. Thanks for taking the questions. Congratulations on a great quarter and even more impressive guide. Can you talk a little bit about the trajectory in Europe and maybe what contribution of the guidance is coming from Europe? I know you mentioned in the prepared remarks the launch will start in Germany, but can you maybe just talk us through the cadence of how the countries come online and who's doing the actual selling? And just as a follow up, you've talked now about the $2 billion peak revenues. How do you think about how long it might take to get to peak revenues?

嗨，早安。感謝您提出問題。恭喜您取得了出色的季度業績和更令人印象深刻的指南。您能否談談歐洲的發展軌跡以及歐洲對指南的貢獻？我知道您在準備好的演講中提到該產品將在德國啟動，但您能否向我們介紹一下這些國家/地區如何上線以及誰在進行實際銷售的節奏？作為後續，您現在談到了 20 億美元的高峰收入。您如何看待收入達到高峰可能需要多長時間？

Yeah, Ren. Thank you for those questions. Christy, do you want to talk about European peak actually?

是的，任。謝謝你提出這些問題。克里斯蒂，你真的想談歐洲巔峰嗎？

Sure. Thanks Ren. So we were pleased to see the European approval come through before the end of last year. As I think everyone knows and even more pleased to see that we saw ISM patients being treated in Germany even before the holidays, which was great to see. So we're out of the gates in Europe and ISM. Germany is really going to be the primary market that's driving ISM this year, due to the cadence of pricing and reimbursement. So other markets will start to come online, but I would expect that more towards kind of end of this year into next year.

當然。謝謝任。因此，我們很高興看到歐洲在去年年底之前獲得批准。我想每個人都知道，更高興的是我們在假期之前就看到 ISM 患者在德國接受治療，這真是太好了。所以我們已經走出了歐洲和 ISM 的大門。由於定價和報銷的節奏，德國確實將成為今年推動 ISM 的主要市場。因此，其他市場將開始上線，但我預計今年年底到明年會出現更多情況。

I think the important thing is if we're thinking about from a revenue perspective, certainly our guide does encompass international and that's yet another variable actually, we think about sort of the guidance range as that launch gets underway. My general expectation is that if you look at the percent of revenue that the international business contributed to AYVAKIT, say in 2023, it's probably going to be roughly in the same range as the US continues to grow very robustly. So, 10-ish percent plus or minus is probably not a bad assumption there to think about Europe.

我認為重要的是，如果我們從收入的角度考慮，當然我們的指南確實涵蓋了國際市場，這實際上是另一個變量，隨著發布的進行，我們會考慮某種指導範圍。我的整體預期是，如果你看看國際業務為 AYVAKIT 貢獻的收入百分比，例如 2023 年，它可能會與美國繼續強勁增長的情況大致相同。因此，對於歐洲來說，10%左右的上下浮動可能並不是一個糟糕的假設。

In terms of the peak, I think again, Kate mentioned, we're on a very clear trajectory that I think looks a lot like other rare disease launches, the time to peak in those launches, you know, it varies, right? These are never markets that are sort of up to saturation within two or three years, and then flattening. I expect AYVAKIT revenue to drive growth for Blueprint for several years to come. One thing that I think is often interesting about time to peak is that there is often a positive relationship between time to peak and what the peak is.

就峰值而言，我再次想到，凱特提到，我們正處於一個非常清晰的軌跡上，我認為它看起來很像其他罕見疾病的發布，這些發布的峰值時間，你知道，它各不相同，對吧？這些市場絕不會在兩三年內達到飽和，然後趨於平緩。我預計 AYVAKIT 營收將在未來幾年推動 Blueprint 的成長。我認為關於達到峰值時間經常有趣的一件事是，達到峰值時間與峰值之間通常存在正相關關係。

So, we just talked about our view of the peak kind of coming up to $2 billion. If you look at markets like HAE, if you look at even Jakafi or Soliris, those drugs have continued to grow and the peak opportunity has also continued to grow because the market grows underneath the drug launch. And so, we'll see what happens. It wouldn't surprise me if our view of the peak continues to evolve as we move through this launch.

所以，我們剛剛討論了我們對 20 億美元高峰的看法。如果你看看像 HAE 這樣的市場，如果你看看 Jakafi 或 Soliris 等市場，你會發現這些藥物持續成長，高峰機會也持續成長，因為市場在藥物上市的情況下成長。所以，我們會看看會發生什麼。如果我們對峰值的看法隨著這次發布的進行而繼續發展，我不會感到驚訝。

Michael Schmidt, Guggenheim.

邁克爾·施密特，古根漢。

Hey, guys, good morning. Thanks for taking my question. I had one on BLU-808. As we sort of head towards AAAAI next week, how do you think about the overall development opportunity for this oral wild-type KIT inhibitor? And talk a bit about how you see potential for differentiation from biologics that are in development for a wild-type kit? Thanks so much.

嘿，夥計們，早安。感謝您提出我的問題。我在 BLU-808 上有一個。下週我們即將迎來 AAAAI，您如何看待這種口服野生型 KIT 抑制劑的整體開發機會？並談談您如何看待與正在開發的野生型試劑盒的生物製劑的差異化潛力？非常感謝。

Thank you, Michael. We're really excited about BLU-808. Fouad, do you want to talk a little bit more about that?

謝謝你，麥可。我們對 BLU-808 感到非常興奮。Fouad，你想再談這個嗎？

Thank you, Michael. So a lot our question first, I have to say I'm very happy today to see a proof-of-concept having been achieved in inhibit -- by inhibiting wild-type KIT with a strategy using monoclonal antibodies. So the POC is there. Now, BLU-808 is a small molecule TK inhibitor that is highly wild-type KIT, very selective, which will have a promise and safety profile as we run the [SAB/MAB] studies, I believe. It is very flexible way to administer a drug and it will be very simple to give compared to all the strategies.

謝謝你，麥可。首先，我們的問題很多，我必須說，今天我很高興看到透過使用單株抗體的策略抑制野生型 KIT，在抑制方面實現了概念驗證。所以 POC 就在那裡。現在，BLU-808 是一種小分子 TK 抑制劑，它是高度野生型 KIT，非常有選擇性，我相信，當我們進行 [SAB/MAB] 研究時，它將具有前景和安全性。這是一種非常靈活的給藥方式，與所有策略相比，給藥都非常簡單。

The most important thing that in my opinion will be a key inflection pointing for us in BLU-808, is the safety and pharmacology data that we will gather from the [SAB/MAB]. After that, I think the POC of wild-type could be the superior strategy of inhibition in CSU has already been shown in some Phase 2 data.

我認為 BLU-808 中最重要的一點是我們將從中收集的安全性和藥理學數據[SAB/MAB]。之後，我認為野生型的 POC 可能是 CSU 的更好的抑制策略，這已經在一些 2 期數據中得到了證明。

Beyond CSU or chronic spontaneous urticaria, there is cold and used urticaria as we all know, but overall mast cell, as I mentioned in my earlier remarks has been really underappreciated target in Type 2 inflammation. And now that we started knowing this in our industry, IBD, the opportunity to leverage blow it weight and wild-type KIT inhibition overall in the number of inflammatory disorders such as Type 2 asthma or MCAS and others, will be very important. I think patients will -- at the end of the day, like an oral agent that we can die up and down depending on the need for the diseases.

除了 CSU 或慢性自發性蕁麻疹之外，眾所周知，還有寒冷性蕁麻疹和二手性蕁麻疹，但正如我在先前的評論中提到的，整體肥大細胞在 2 型發炎中確實被低估了。現在我們開始在 IBD 行業中了解這一點，在 2 型氣喘或 MCAS 等發炎性疾病中充分利用野生型 KIT 抑制的機會將非常重要。我認為患者最終會像口服藥物一樣，根據疾病的需要而上下死亡。

Yeah, thanks Fouad for this. I just wanted to add one thing. This is Becker. I get the question a lot about how a wild-type KIT inhibitor, what might compare with what is currently being developed. And I think one thing to remember is we're talking about a very wide spectrum of disease with different manifestations and different tissues and different levels of severity, and using a blunt instrument like an antibody that might eliminate a number of mast cells isn't where you want to go with a lot of these diseases. And so we think that at tuneable solution that is -- we can titrate to what each patient or patient population needs is the right thing in this population or in these diseases.

是的，謝謝福阿德。我只是想補充一件事。這是貝克爾。我收到很多關於野生型 KIT 抑制劑如何與目前正在開發的抑制劑進行比較的問題。我認為要記住的一件事是，我們正在談論一種非常廣泛的疾病，具有不同的表現、不同的組織和不同的嚴重程度，並且使用像抗體這樣可能消除大量肥大細胞的鈍器是不可行的。你想去的地方有很多這樣的疾病。因此，我們認為，在可調整的解決方案中，我們可以滴定到每個患者或患者群體的需求，這對於該族群或這些疾病是正確的。

The other thing to remember is that most of these approach, whether it's BTK or antibodies, don't directly address the true driver of the mast cell, which is KIT. BTK inhibits activation and degranulation but really doesn't address the biology of the mast cells and even the antibodies they're active in asthma are really an orthogonal approach to the disease methodology. So really KIT is the Achilles heel of these diseases.

另一件要記住的事情是，大多數這些方法，無論是 BTK 還是抗體，都無法直接解決肥大細胞的真正驅動因素，即 KIT。BTK 抑制活化和脫顆粒，但實際上並沒有解決肥大細胞的生物學問題，甚至它們在氣喘中活躍的抗體實際上也是疾病方法學的正交方法。所以 KIT 確實是這些疾病的致命弱點。

Thank you.

謝謝。

Derek Archila, Wells Fargo.

德里克·阿奇拉，富國銀行。

Hey, good morning and congrats on the results here. Just two questions from us. You talked about kind of an increasing rate of diagnosis for ISM. I guess I'm just curious, do you think current estimates might be still slow for the number of patients out there? And I guess, what inning do you think we are in terms of the increasing diagnosis rate? And then just as a follow up, any additional kind of quantitative color on the current discontinuation rate you're seeing?

嘿，早安，祝賀這裡的結果。我們只有兩個問題。您談到了 ISM 診斷率的增加。我想我只是好奇，你認為目前對患者數量的估計可能仍然緩慢嗎？我想，您認為診斷率上升到了第幾局？然後，作為後續行動，您所看到的當前停藥率是否有任何其他類型的定量顏色？

Thank you, Derek for the question. Maybe just starting with the epidemiology. I mean, we updated epidemiology at JP Morgan. We've seen really nice growth in the diagnosis of SM that is predominantly ISM, right. Because advanced SM patients are -- have a smaller or less intense diagnostic odyssey just given the manifestations of that disease. And we're in very early innings on understanding the size of this market and we anticipate it'll continue to grow very substantially over the next set of years.

謝謝德里克的提問。也許只是從流行病學開始。我的意思是，我們更新了摩根大通的流行病學。我們已經看到 SM 診斷的成長非常快，主要是 ISM，對吧。因為晚期 SM 患者－僅考慮到該疾病的表現，就需要進行較小或較不強烈的診斷過程。我們正處於了解這個市場規模的早期階段，我們預計它將在未來幾年繼續大幅成長。

Just as Christy talked about what we've seen in other rare disease launches. So anyone want to talk a bit about the durability we're seeing and how that becomes such a big part of the kind of future value prospect of AYVAKIT?

正如克里斯蒂談到我們在其他罕見疾病發布會上所看到的那樣。那麼有人想談談我們所看到的耐用性以及它如何成為 AYVAKIT 未來價值前景的重要組成部分嗎？

Yes, sure. We have been really pleased to see the clinical profile of AYVAKIT really playing out positively in terms of real world experience. Compliance has been really high and while we're really early in the launch, but very low discontinuation rates which bode well for chronic durations of therapy with AYVAKIT. And at this point in the launch, as we continue to add more patients that duration and the cumulative impact of adding more patients and more patients staying on therapy is going to be a substantial contributor to the revenue growth going forward.

是的，當然。我們非常高興看到 AYVAKIT 的臨床概況在現實世界的經驗方面確實發揮了積極作用。依從性非常高，雖然我們還處於推出初期，但停藥率非常低，這對 AYVAKIT 的長期治療來說是個好兆頭。在推出的這個階段，隨著我們繼續增加更多的患者，持續時間以及增加更多患者和更多接受治療的患者的累積影響將成為未來收入成長的重大貢獻者。

Understood. Thank you.

明白了。謝謝。

Laura Prendergast, Raymond James.

勞拉·普倫德加斯特，雷蒙德·詹姆斯。

Hey, guys, Congrats on the big day today. Very exciting to see. Just two questions from me. First, what is driving these new patients starts? Do you think it's more so from the patient awareness side or education from providers during routine visits?

嘿，夥計們，恭喜今天是個大日子。非常令人興奮。我只想問兩個問題。首先，是什麼推動了這些新患者的開始？您認為這更多的是來自患者意識方面還是來自提供者在例行就診期間的教育？

And then my second question is as you guys think about the CDK2 partnerships, is this focusing on just partnering the BLU-222 asset or are you more so thinking about partnering the whole CDK2 franchise in the next gen and the degrader you guys brought up at JP Morgan?

然後我的第二個問題是，當你們考慮 CDK2 合作夥伴關係時，這只是專注於與 BLU-222 資產合作還是你們更考慮在下一代和你們養大的降級者中與整個 CDK2 特許經營合作摩根大通？

Yeah, thank you Laura for the question. Philina, do you want to talk a little bit about how we see the drivers new patients starts, then Christy, we'll hand it over to you to talk about this development around CDK2.

是的，謝謝勞拉提出的問題。Philina，您想談談我們如何看待新患者啟動的驅動程式嗎？然後 Christy，我們將把它交給您來討論圍繞 CDK2 的開發。

Yeah, thanks for the question Laura. We entered the launch already with strong awareness among our targeted hemoc and AI. Initially the drivers, obviously some of the hemocs were coming in with experience with AYVAKIT from advanced SM. That was what we shared in some of our very earliest adoptions. But what's honestly been really exciting to see is an expansion in the breadth of new prescribing, in hematology oncology as well.

是的，謝謝勞拉提出的問題。我們在啟動時就已經對我們的目標 hemoc 和人工智慧有了強烈的認識。最初的司機，顯然有些 hemocs 是從先進的 SM 那裡獲得 AYVAKIT 經驗的。這就是我們在一些最早的收養中所分享的內容。但說實話，真正令人興奮的是新處方範圍的擴大，血液腫瘤學也是如此。

They are motivated, they are so much more excited about ISM and the opportunity and the need here as well as an increasing proportion of allergy immunology who are prescribing. Significant growth to date there, significant headroom to grow, as we've said.

他們充滿動力，對 ISM 以及這裡的機會和需求以及越來越多的過敏免疫學患者開處方感到更加興奮。正如我們所說，迄今為止，該地區增長顯著，增長空間巨大。

To date, the majority of that growth has been driven by provider engagement. We've talked about how out of the gate we have made available a lot of really patient facing, initiatives and JP Morgan, we shared that we almost doubled patient awareness of AYVAKIT, which activates them to speak to their provider about it.

迄今為止，大部分的成長都是由提供者參與推動。我們已經討論過我們如何從一開始就提供了許多真正面向患者的舉措和摩根大通，我們分享了我們幾乎使患者對 AYVAKIT 的認識增加了一倍，這促使他們與他們的提供者談論這一點。

But I would say with the patient activation that's early days and that's even more headroom to grow on that front. We know patients are a critical stakeholder in this type of chronic disease where they're a key part of that shared decision making with their providers.

但我想說，隨著患者的激活，這還處於早期階段，在這方面還有更大的發展空間。我們知道，患者是此類慢性病的關鍵利益相關者，他們是與醫療服務提供者共同決策的關鍵部分。

And so this year, we're really embarking on deeper direct to patient initiatives to promote, increase the awareness of AYVAKIT and really encourage them to seek options that can give them better disease control. We're excited to share more about that. And we're also doing that I should say in a very resource effective way based on our deep knowledge of where these patients are going to look for information, learn about the disease and engage with providers.

因此，今年，我們真正開始開展更深入的直接面向患者的舉措，以促進、提高 AYVAKIT 的認識，並真正鼓勵他們尋求能夠更好地控制疾病的選擇。我們很高興能分享更多相關內容。我應該說，我們也在以一種非常資源有效的方式這樣做，基於我們對這些患者將在哪裡尋找資訊、了解疾病並與提供者接觸的深入了解。

And one thing I would just add to that is, nothing is as impactful to patients as hearing from other patients who've been on the therapy. And now that as we see here today where we're over a thousand patients, estimate a thousand patients in the US and we see patients who are on therapy sharing those experiences in chat rooms and online. And we're also have some more formalized programming around that where we can connect patients who are on AYVAKIT, with patients who are considering it as a therapy, which I think is going to be very impactful this year. Christy, do you want to talk about the CDK2?

我想補充的一件事是，沒有什麼比聽取其他接受過治療的患者的意見更能影響患者的了。現在，正如我們今天在這裡看到的，我們有超過一千名患者，估計美國有一千名患者，我們看到正在接受治療的患者在聊天室和網路上分享這些經驗。我們還制定了一些更正式的計劃，可以將使用 AYVAKIT 的患者與考慮將其視為療法的患者聯繫起來，我認為這將在今年產生非常大的影響。Christy，你想談談 CDK2 嗎？

Sure. So as you said, we have a significant amount of strategic interest in the target, right? I think the target is clearly now one that's going to be incredibly important to any company that wants to be a player in the breast cancer market going forward. The focus of conversation from a BD perspective has been on 222 certainly. We have a next generation asset that could be a part of those conversations we're exploring and open to different possibilities there. But I think there's also a lot of interest in our degrader platform broadly. And we really look at that as essentially a different modality and approach to addressing this target. So, we'll see how these conversations evolve. Certainly open to different collaboration structures, but our overall goal is really maximizing the value of the franchise in totality.

當然。正如您所說，我們對該目標擁有大量戰略利益，對嗎？我認為現在的目標顯然對於任何想要成為乳癌市場參與者的公司來說都非常重要。從 BD 的角度來看，談話的焦點當然是 222。我們擁有下一代資產，它可以成為我們正在探索的對話的一部分，並對那裡的不同可能性持開放態度。但我認為人們對我們的降解器平台也很感興趣。我們確實將其視為實現這一目標的本質上不同的模式和方法。因此，我們將看看這些對話如何演變。當然對不同的合作結構持開放態度，但我們的總體目標實際上是最大化特許經營的整體價值。

Great, thank you. And just when can we expect to see more information on this degrader platform?

太好了謝謝。我們什麼時候可以看到有關這個降級器平台的更多資訊？

Fouad, do you want to talk a little bit more about that?

Fouad，你想再談這個嗎？

We are very happy with the variety of the progress that we made on our degrader platform. As you may remember, we started this a little bit more than two years ago. And today we have a number of degraders in development. We mentioned CDK2 degraders in the cyclin dependent kinase space, but this is only the tip of the iceberg that we and that Kate shared at the JP Morgan conference. I think down the road, you will see some good degraders CDK2 clearly other targets are our key targets in the treatment of cancer. And we will really give more timeline and guidance as we get closer and ready to share that type of information.

我們對我們在 degrader 平台上取得的各種進展感到非常滿意。您可能還記得，我們​​在兩年多前就開始了這項工作。今天我們有許多降解劑正在開發中。我們提到了細胞週期蛋白依賴性激酶領域中的 CDK2 降解劑，但這只是我們和 Kate 在摩根大通會議上分享的冰山一角。我認為在未來，你會看到一些良好的 CDK2 降解劑，顯然其他標靶是我們治療癌症的關鍵標靶。當我們越來越接近並準備好分享此類資訊時，我們確實會提供更多的時間表和指導。

And I think one other thing to mention too is, and I know we said it in our press release, I mean, we're also doing quite a bit of work in the mast cell and looking at other mast cell driven targets as well. And so stay tuned on that as we move forward.

我認為另一件事也值得一提，我知道我們在新聞稿中說過，我的意思是，我們還在肥大細胞方面做了相當多的工作，並研究了其他肥大細胞驅動的目標。因此，隨著我們的進展，請繼續關注這一點。

Mike Ulz, Morgan Stanley.

麥克烏爾茲，摩根士丹利。

Hi, good morning. This is [Rohan] on from Mike. Can you just talk about the breakdown of your 2024 guidance? How much do you attribute to ASM versus ISM? And then can you talk about any trends you're seeing thus far for 2024? Thank you.

早安.這是麥克的[Rohan]。能簡單談談您對 2024 年指引的具體分析嗎？與 ISM 相比，您對 ASM 的貢獻有多大？那麼您能談談迄今為止您所看到的 2024 年趨勢嗎？謝謝。

Yes, Christy, do you want to take the guide? I mean, the one thing I'll say about 2024 is that we're a few weeks in here where -- this is our first experience with the Q1 dynamics that Christy mentioned. You see often in pharma with ISM. So we're just -- teams working through that well to see how that plays out. But really the underlying demand from both new and existing patients appears very strong this year and very early days. Christy, do you want to talk about the guidance?

是的，克里斯蒂，你想跟著導遊嗎？我的意思是，關於 2024 年，我要說的一件事是，我們已經在這裡待了幾週了——這是我們第一次體驗克里斯蒂提到的第一季動態。您經常在製藥廠看到 ISM。所以我們只是——團隊正在努力解決這個問題，看看結果如何。但實際上，今年和早期的新患者和現有患者的潛在需求似乎都非常強勁。克里斯蒂，你想談談指導嗎？

Sure. So as you all have heard us say many times, we don't break out revenue by indication. However, ISM is clearly driving our revenue growth, right? We've seen that clear inflection upon the first two quarters of launch and I think if you look at the revenue trajectory Rohan, it's obviously that growth is coming from ISM.

當然。正如你們多次聽到我們說過的那樣，我們不會按指標來細分收入。然而，ISM 顯然正在推動我們的營收成長，對嗎？我們已經看到了發布前兩個季度的明顯變化，我認為如果你看看 Rohan 的營收軌跡，很明顯成長來自 ISM。

Philina shared that more than 70% of our new starts are coming at the 25 milligram dose, which is an imperfect sort of way of looking at ISM. But I think it's a relevant data point that again, just highlights that we're really seeing the growth coming from ISM and would expect that to continue well into the future, as we capitalize on this $2 billion opportunity for AYVAKIT.

Philina 表示，我們超過 70% 的新產品採用的是 25 毫克劑量，這是看待 ISM 的一種不完美的方式。但我認為這是一個相關的數據點，再次強調我們確實看到了 ISM 帶來的成長，並預計這種成長將持續到未來，因為我們利用了 AYVAKIT 的這個 20 億美元的機會。

As Kate said, we are early in Q1. The one thing I would highlight is we were really pleased to hit the thousand patient marks in January. So I think that speaks to certainly the continued demand that we're seeing in terms of new patient starts, et cetera. That we're seeing. There's other dynamics in Q1 that I wouldn't be surprised if we faced our first quarter of launch.

正如凱特所說，我們處於第一季的早期。我要強調的一件事是，我們非常高興在一月達到了一千名病患的目標。因此，我認為這肯定說明了我們在新患者開始等方面看到的持續需求。我們正在看到。第一季還有其他動態，如果我們面對第一季的發布，我不會感到驚訝。

Certainly in my previous experience, especially in these types of chronic immunology markets, you do often see hits around compliance, growth to net and copay dynamics, et cetera. So we're only part of the way through the quarter, obviously. We'll see how that all plays out. But Q1 is often more of a challenging one. Just if you look at quarter on quarter dynamics of the year.

當然，根據我先前的經驗，尤其是在這些類型的慢性免疫學市場中，您確實經常會看到有關合規性、淨成長和共付動態等方面的問題。顯然，本季我們只完成了一部分。我們將看看這一切如何進行。但第一季往往更具挑戰性。只要你看看一年中每季的動態就知道了。

Matt Biegler, Oppenheimer.

馬特·比格勒，奧本海默。

Hi guys, congrats from us as well. Can you give us more granularity on the prescriber mix? I think last quarter, we saw around 25% of new scripts from allergists, like has that figure continued to increase? And also what's the contribution of dermatologists and GI docs as well? Thanks.

大家好，我們也向您表示祝賀。您能否為我們提供更多有關處方組合的詳細資訊？我想上個季度，我們看到大約 25% 的新處方來自過敏症專家，這個數字是否還在繼續增加？皮膚科醫生和胃腸科醫生也做出了哪些貢獻？謝謝。

Yeah, thanks Matt. I’ll hand that to Philina. I mean we've been really pleased to see that contribution from allergist immunology, which is a key prescriber target for us has continued to grow. Philina, do you want to talk more about that?

是的，謝謝馬特。我會把它交給菲莉娜。我的意思是，我們非常高興看到過敏免疫學的貢獻不斷增長，這是我們的關鍵處方目標。菲莉娜，你想再談這個嗎？

Yeah. Thanks for the question Matt. We do continue to see the allergist contribution grow. It's now over 30% probably in the mid-30s. I think we had talked about 20%, 25% previously. We're really excited to be motivating this prescriber base among allergists. It's also adoption among the academic as well as the community setting. They're finding AYVAKIT easy. They're obviously very attuned to the symptom management and the quality of life impacts of ISM on these patients and are motivated to try a disease modifying option.

是的。謝謝馬特的提問。我們確實繼續看到過敏症專家的貢獻不斷增長。現在大概在30多歲左右，這個比例已經超過30%了。我想我們之前討論過20%、25%。我們非常高興能夠激勵過敏症專家中的處方者基礎。它也在學術界和社區環境中被採用。他們發現 AYVAKIT 很容易。他們顯然非常了解 ISM 對這些患者的症狀管理和生活品質影響，並有動力嘗試疾病改變方案。

Among derm and GI, in our experience derm and GI it's really much more of a referring specialty, whereas allergist immunologists and hematologist, oncologists are the primary prescribing specialties. And that really has been our focus to date from a promotional standpoint.

在皮膚和胃腸道中，根據我們的經驗，皮膚和胃腸道實際上更多的是轉介專業，而過敏免疫學家和血液學家、腫瘤學家是主要的處方專業。從促銷的角度來看，這確實是我們迄今為止的重點。

For example, when you look at the top 400 treaters that is completely dominated by hemoc and AI, and that continues to be our primary focus to drive the adoption where we're most likely to see repeat prescribing. When it comes to derm and GI, I would say, they do play an important role in diagnosis and multidisciplinary care and so we do have other sort of arms of educating to help these specialties identify patients.

例如，當您查看完全由 hemoc 和 AI 主導的前 400 名治療師時，這仍然是我們推動最有可能看到重複處方的採用的主要焦點。當涉及皮膚和胃腸道時，我想說，它們確實在診斷和多學科護理中發揮重要作用，因此我們確實有其他類型的教育部門來幫助這些專業識別患者。

And just to add to that, our medical team has done a really great job here actually, and they've been focusing on some of these other specialties to Philina’s point, but making sure we're finding kind of the right medical dermatologist, who actually have an interest in SM, CSM patients and tend to be kind of part of those patient's journeys. And it's a full group effort here but as the allergy, immunology and hematology, oncology are going to be the drivers of this opportunity for the foreseeable future.

除此之外，我們的醫療團隊在這裡實際上做得非常出色，他們一直專注於菲利娜的其他一些專業，但要確保我們找到合適的醫療人員皮膚科醫生，他們實際上對SM、CSM患者感興趣，並且往往成為這些患者旅程的一部分。這是整個團隊的努力，但在可預見的未來，過敏學、免疫學和血液學、腫瘤學將成為這個機會的驅動力。

Ami Fadia, Needham.

阿米法迪亞，尼達姆。

Thank you. Let me add my congratulations on the strong quarter and guidance. But I had a follow-up on guidance and I'm trying to square away what are some of the variables, as I think about what the guidance implies, it seems to be that in fourth quarter you had added more than 200 patients and guidance implies roughly a little over a 100 patient ads per quarter. So what are some of the other variables we should be thinking about? What's your assumption with regards to discontinuation of patients from the thousand patients that you have -- and had in January? And then how should we think about duration of treatment? And is there any other sort of important variables we should be thinking about?Thank you.

謝謝。讓我對強勁的季度業績和指導表示祝賀。但我對指導進行了後續跟踪，我正在嘗試消除一些變量，當我思考指導意味著什麼時，似乎在第四季度您增加了 200 多名患者和指導意味著每個季度大約有100 多個患者廣告。那我們應該考慮哪些其他變數呢？對於您一月份收治的數千名患者中的停藥，您有何假設？那我們該如何考慮治療的持續時間呢？我們還應該考慮其他類型的重要變數嗎？謝謝你。

Yeah, thanks Amy. Christy, do you want to dive into guidance a bit?

是的，謝謝艾米。克里斯蒂，你想深入了解一下指導嗎？

Sure. Ami, I would say the guidance does not imply that and I would -- I know Mark asked a similar question earlier. There's a range of assumptions on each of these variables that you can kind of think about to get into that guidance range. We're obviously thinking about a number of inputs here. So, new patients prescribed discontinuation rates.

當然。阿米，我想說的是，指導意見並不意味著這一點，而且我會——我知道馬克早些時候問過類似的問題。對於每個變數都有一系列假設，您可以考慮將其納入該指導範圍。顯然，我們在這裡考慮了一些輸入。因此，新患者規定了停藥率。

Both of those things kind of impact net patient ads on a quarter, factors like compliance, what our percent of free drug looks like, et cetera, and then we talked about the international launch. You could probably get to more than a thousand scenarios, if you play with those variables depending on the assumptions. And I think there's some people at Blueprint that have probably done that.

這兩件事都會影響一個季度的淨患者廣告，諸如合規性、我們的免費藥物百分比等因素，然後我們討論了國際發布。如果您根據假設來處理這些變量，您可能會遇到一千多個場景。我認為 Blueprint 的一些人可能已經做到了這一點。

But what's safe to say is that our first couple of quarters of launch and our experience there really set the foundation for sort of what are the key assumptions that we're taking forward. And certainly one of those is that we're continuing -- we're going to continue to have very steady, consistent, new patient starts and discontinuation rates that are very much in line with what we've been seeing, which support extended durations of therapy that we think could be multiple years.

但可以肯定地說，我們發布的前幾季和我們在那裡的經驗確實為我們正在推進的關鍵假設奠定了基礎。當然，其中之一是我們正在繼續——我們將繼續保持非常穩定、一致的新患者入院率和停藥率，這與我們所看到的情況非常一致，這支持延長治療期限我們認為治療可能需要多年。

That is sort of the forms of foundation of our assumptions based on the last two quarters of experience. That was where we started. And then you kind of think about reasonable ranges and assumptions around each of those things. And that really informed how we got to the guidance range.

這就是我們根據過去兩個季度的經驗所做的假設的基礎形式。這就是我們開始的地方。然後你會思考圍繞每件事的合理範圍和假設。這確實告訴我們如何達到指導範圍。

Peter Lawson, Barclays.

彼得·勞森，巴克萊銀行。

Thanks for the update and guidance and all the details. Was there anything that happened during 4Q or the P&L of 1Q that kind of changes the view that GS and SM revenues should essentially be flat in '24?

感謝您的更新和指導以及所有詳細資訊。第四季或第一季損益表中是否發生了任何事情改變了 GS 和 SM 收入在 24 年基本持平的觀點？

Yeah, thanks Peter for that question. I mean, the answer is no, but I know if you have any more color, I mean, we've been very just as consistent. I mean, we have said for maybe 18 months now that just, it contributes about $8, $9 a quarter. That is steady Eddie. That is been very, very consistent quarter over quarter for a long period of time. Now, SM continues to have growth in it, it's just not the same growth rate as ISM. And Christy do you want to talk about that?

是的，謝謝彼得提出這個問題。我的意思是，答案是否定的，但我知道如果你還有更多的顏色，我的意思是，我們一直都非常一致。我的意思是，我們已經說過大約 18 個月了，它每季貢獻約 8 美元、9 美元。那是穩定的艾迪。在很長一段時間內，每季的情況都非常非常一致。現在，SM持續成長，只是與ISM的成長速度不一樣。克里斯蒂，你想談談這個嗎？

Yeah. The short answer, Peter, is no. The launch is not flattening. I think that our guidance is the clearest signal of that with over 80% of growth at the midpoint and all leading indicators being very positive.

是的。彼得，簡短的回答是否定的。發射並沒有趨於平緩。我認為我們的指導是最明確的訊號，中間成長超過 80%，所有領先指標都非常正面。

Colleen Kusy, Baird.

科琳·庫西，貝爾德。

Great. Thanks. Good morning. Congrats on the progress and thanks for taking our questions. So I think you talked about 20% of the top 400 docs based on volume have prescribed AYVAKIT. So is those 80% of docs that haven't, can you explain, again, what's been the hurdle for them and what might convince them to start prescribing AYVAKIT?

偉大的。謝謝。早安.恭喜您的進展，並感謝您提出我們的問題。所以我認為您談到了根據數量排名前 400 名的醫生中有 20% 開出了 AYVAKIT 處方。那麼，對於 80% 的醫生來說，您能再次解釋一下他們面臨的障礙是什麼以及什麼可能說服他們開始開 AYVAKIT 處方嗎？

Yes, so Philina, you should dive in here. Just to be clear that's been since the ISM approval. Just to be clear, we're trying to track here like physicians who see FM generally, but we're looking at the -- we can't, as Christy has said, Philina, we can't really distinguish between advanced SM and ISM all the time based on diagnosis codes. We do look at the dosage 25 milligram as an imperfect proxy for that. So this is really looking at the physicians who have been prescribing since Q3 and Q4, right? So, I don't know Philina, if you want to talk?

是的，所以菲莉娜，你應該潛入這裡。需要明確的是，這是自 ISM 批准以來的情況。需要明確的是，我們試圖像醫生一般檢查 FM 一樣在這裡進行跟踪，但我們正在研究 - 我們不能，正如克里斯蒂所說，菲莉娜，我們無法真正區分高級 SM 和ISM 始終基於診斷代碼。我們確實將 25 毫克劑量視為對此的不完美替代品。所以這實際上是在關注自第三季和第四季以來一直在開處方的醫生，對嗎？那麼，我不認識菲莉娜，你想談談嗎？

This is a market where the cadence, the timing of patient visits is a really critical factor in when they're able to engage and have that conversation about indolent SM with their providers. And so, I would say at this point, this early in the launch, we're actually really excited to have had penetration into 20% of this group, with room to grow the adoption both within that group as well as broadening beyond to those who haven't.

在這個市場中，患者就診的節奏和時間是他們能否與醫療服務提供者就惰性 SM 進行互動和對話的真正關鍵因素。因此，我想說，在這一點上，在發布的早期階段，我們真的很高興能夠滲透到該群體的 20%，並且在該群體內以及擴大到其他群體的採用方面都有空間。誰沒有。

I would say awareness among this group is very strong. They are all having personally engaged a number of these providers, they're all motivated, they are excited about AYVAKIT's benefit risk profile, and they're waiting for those next patients to come in and have that conversation.

我想說這個群體的意識非常強烈。他們都親自與許多這樣的提供者接觸，他們都很積極，他們對 AYVAKIT 的利益風險狀況感到興奮，他們正在等待下一批患者進來並進行對話。

That's helpful. Thank you.

這很有幫助。謝謝。

We are coming up on the hour and going to end the call. Ms. Haviland, I turn the call back over to you.

我們準時到了並要結束通話。哈維蘭女士，我將電話轉回給您。

Thank you, operator. And I want to thank you all for taking the time to join us today and thank you for your questions. We look forward to seeing you in the near-term here, many of you at AAAAI in Washington DC and so, have a great day and we'll see you soon.

謝謝你，接線生。我要感謝大家今天抽出時間加入我們，並感謝你們提出的問題。我們期待在不久的將來在這裡見到您，華盛頓特區 AAAI 的許多人，祝您度過愉快的一天，我們很快就會見到您。

That concludes today's call. You may now disconnect your line.

今天的電話會議到此結束。現在您可以斷開線路。