SpringWorks Therapeutics Inc (SWTX) 2024 Q3 法說會逐字稿

Good morning. My name is Tanya, and I will be your conference operator today. At this time, I would like to welcome everyone to the SpringWorks Therapeutics third quarter 2024 earnings conference call. (Operator Instructions)

早安.我叫 Tanya，今天我將擔任您的會議主持人。現在，我歡迎大家參加 SpringWorks Therapeutics 2024 年第三季財報電話會議。（操作員指令）

Thank you. I would now like to turn the conference over to Kim Diamond, Vice President of Corporate Communications at SpringWorks Therapeutics. Kim, you may now begin the conference.

謝謝。現在，我想將會議交給 SpringWorks Therapeutics 公司企業傳播副總裁 Kim Diamond。金，現在你可以開始會議了。

Thank you, and good morning, everyone. Welcome to the SpringWorks Therapeutics third quarter 2024 earnings conference call. This morning, we issued a press release, which outlines our financial and operational results for the third quarter. You can access the press release as well as the slides that we will be presenting today by going to the Investors & Media section of our website at www.springworkstx.com.

謝謝大家，早安。歡迎參加 SpringWorks Therapeutics 2024 年第三季財報電話會議。今天早上，我們發布了一份新聞稿，概述了我們第三季的財務和營運表現。您可以透過造訪我們網站 www.springworkstx.com 的投資者和媒體部分來存取新聞稿以及我們今天將要展示的幻燈片。

Joining me today are Saqib Islam, Chief Executive Officer; Bhavesh Ashar, Chief Commercial Officer; Dr. Jim Cassidy, Chief Medical Officer; Frank Perier, Chief Financial Officer; and Dr. Badreddin Edris, Chief Operating Officer.

今天與我一起出席的還有執行長 Saqib Islam； Bhavesh Ashar，首席商務長；首席醫療官 Jim Cassidy 博士；佩里爾 (Frank Perier)，財務長；以及營運長 Badreddin Edris 博士。

Before we begin, I would like to remind you that some of the statements made during the call today are forward-looking statements that 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 SpringWorks disclaims any obligation to update statements.

在我們開始之前，我想提醒您，今天電話會議中發表的一些陳述是前瞻性陳述，受許多風險和不確定性的影響。這些可能會導致我們的實際結果大不相同，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，且 SpringWorks 不承擔更新陳述的任何義務。

I will now turn the call over to Saqib.

現在我將電話轉給薩奇布。

Thank you, Kim, and thank you all for joining this morning. I'm pleased to share our third quarter results as well as an update on how we are delivering on our objective to make a profound impact on the lives of patients with devastating diseases.

謝謝你，金，也謝謝大家今天早上的參加。我很高興與大家分享我們第三季度的業績以及我們如何實現目標以對患有毀滅性疾病的患者的生活產生深遠影響的最新進展。

Starting with OGSIVEO, for patients with desmoid tumors, we are very pleased with the continued strong momentum of our US launch. In the third quarter, we reported $49.3 million in net product revenue, which represents a 23% growth quarter-over-quarter. This strong and steady growth is driven by robust demand, both from new patient starts as well as existing patients who are continuing to experience meaningful antitumor activity and substantial improvements in their quality of life on OGSIVEO.

從 OGSIVEO 開始，對於患有纖維瘤的患者來說，我們對美國上市的持續強勁勢頭感到非常高興。第三季度，我們報告的淨產品收入為 4,930 萬美元，季增 23%。這種強勁而穩定的成長是由強勁的需求推動的，無論是來自新患者還是現有患者，他們都在繼續體驗有意義的抗腫瘤活性以及 OGSIVEO 對其生活品質的顯著改善。

As we approach one-year mark of our launch, we are very pleased with our progress in making OGSIVEO the standard of care systemic therapy for patients with desmoid tumors. Our commercial execution to date has been exceptional, and our market research shows we have only reached a small portion of people with desmoid tumors who can potentially benefit from OGSIVEO.

隨著我們推出該產品已接近一年，我們對 OGSIVEO 成為纖維瘤患者標準全身治療所取得的進展感到非常高興。我們迄今為止的商業執行非常出色，我們的市場調查顯示，只有一小部分患有纖維瘤的人可能從 OGSIVEO 中受益。

In a few moments, our Chief Commercial Officer, Bhavesh, will highlight key metrics from the launch, including those related to patients, prescribers and evolving treatment trends that inform our view of the significant opportunity ahead of us. In these data, you will see high enthusiasm for OGSIVEO, increasing likelihood and desire to treat and an addressable patient population that appears to be meaningfully larger than initially estimated.

稍後，我們的商務長 Bhavesh 將重點介紹此次發表會的關鍵指標，包括與患者、處方人員和不斷發展的治療趨勢相關的指標，這些指標讓我們了解了未來重大機會。在這些數據中，您將看到人們對 OGSIVEO 的高度熱情、治療的可能性和願望不斷增加，而可處理的患者群體似乎比最初估計的要大得多。

Our conviction is further reinforced by insights we have gained from our early launch and measures we have taken to position ourselves for long-term success. Four key drivers underscore our confidence and the significant opportunity in front of us.

我們從早期發布中獲得的見解以及為長期成功而採取的措施進一步增強了我們的信念。四個關鍵驅動因素凸顯了我們的信心和麵臨的重大機會。

First, this quarter, we successfully introduced 150-milligram and 100-milligram strength tablets of OGSIVEO and blister packaging to increase patient convenience, adherence and renewal times. Second, we now have real-world data that strongly suggests that the addressable patient population is larger than we initially had estimated.

首先，本季度，我們成功推出了 150 毫克和 100 毫克強度的 OGSIVEO 片劑和泡罩包裝，以增加患者的便利性、依從性和更新時間。其次，我們現在擁有的真實數據強烈表明可解決的患者群體比我們最初估計的要大。

Third, we have continued to see very high satisfaction from physicians and expect that the majority will increase their usage of OGSIVEO in the coming year. And fourth, we have continued to generate data on the benefits of longer-term treatment with OGSIVEO.

第三，我們繼續看到醫生的滿意度非常高，並預計大多數醫生將在未來一年增加對 OGSIVEO 的使用。第四，我們繼續收集有關 OGSIVEO 長期治療益處的數據。

We will review all four of these factors over the course of this morning's presentation to highlight our increased confidence that we have only scratched the surface of OGSIVEO's opportunity to benefit patients with desmoid tumors and are poised for success to help this patient community going forward.

我們將在今天早上的演講中回顧所有這四個因素，以強調我們更有信心，我們只觸及了 OGSIVEO 造福纖維瘤患者的機會的表面，並準備成功地幫助這個患者群體向前發展。

Turning to mirdametinib, there is a substantial unmet need for the approximately 40,000 people living with NF1-PN in the United States alone, 30,000 of whom are adults and 10,000 are children. Our NDA for adults and children with NF1-PN was granted priority review, and launch preparations are on track ahead of our February 28 PDUFA date.

談到 mirdametinib，光在美國就有大約 40,000 名 NF1-PN 患者，其中 30,000 名是成人，10,000 名是兒童，因此存在大量未滿足的治療需求。我們針對成人和兒童 NF1-PN 患者的 NDA 已獲得優先審查，上市準備工作正在按計劃於 2 月 28 日 PDUFA 日期之前完成。

Data from our pivotal Phase 2b ReNeu trial formed the basis of NDA and provide the potential for mirdametinib to become the first FDA-approved treatment for adults with NF1-PN and a best-in-class option for children. Our team is excited by the opportunity to deliver a medicine that has the potential to provide deeper responses in existing therapies, a manageable tolerability profile, improved quality of life and a dispersible tablet formation for children and adults unable to swallow pill. We look forward to continuing to work with the FDA throughout the NDA review process, while simultaneously advancing our commercial preparations in anticipation of a potential approval in early 2025.

我們關鍵的 2b 期 ReNeu 試驗的數據構成了 NDA 的基礎，並使 mirdametinib 有可能成為 FDA 批准的首個治療成人 NF1-PN 的藥物以及治療兒童 NF1-PN 的最佳藥物。我們的團隊很高興有機會提供一種藥物，這種藥物有可能在現有療法中提供更深層的反應、可控的耐受性、改善生活質量，並為無法吞嚥藥丸的兒童和成人提供可分散的片劑形式。我們期待在整個 NDA 審查過程中繼續與 FDA 合作，同時推進我們的商業準備以期在 2025 年初獲得批准。

In parallel, we are advancing our efforts to bring our innovative therapies to patients globally, with EU regulatory reviews for OGSIVEO and mirdametinib underway. With the potential for both approvals to come in 2025, we have onboarded European commercial and medical leadership to further advance these efforts and prepare to bring our medicines to market.

同時，我們正在加強將創新療法帶給全球患者，OGSIVEO 和 mirdametinib 正在接受歐盟監管審查。由於這兩項藥物都有可能在 2025 年獲得批准，我們已經與歐洲商業和醫學領導層合作，進一步推進這些努力，並準備將我們的藥物推向市場。

Beyond our work in desmoid tumors and NF1-PN, we continue to advance our emerging portfolio, which Jim Cassidy, will provide an update on later in the call. Lastly, we have a strong balance sheet that we expect to fund us through profitability, which we are on track to achieve in the first half of 2026.

除了在纖維瘤和 NF1-PN 方面的工作外，我們還將繼續推進我們的新興產品組合，Jim Cassidy 將在稍後的電話會議上提供最新資訊。最後，我們擁有強勁的資產負債表，我們預計透過獲利能力為我們提供資金，我們預計在 2026 年上半年實現這一目標。

I'll now turn the call to Bhavesh to discuss our progress with OGSIVEO for patients with desmoid tumors and our prelaunch preparations for mirdametinib for patients with NF1-PN. Bhavesh?

現在我將電話轉給 Bhavesh，討論我們針對纖維瘤患者使用 OGSIVEO 的進展，以及針對 NF1-PN 患者的 mirdametinib 的上市前準備。巴韋什？

Thank you, Saqib. Nearly a year into our launch, OGSIVEO has continued to consolidate and expand its leadership position as the most prescribed systemic therapy for adults with desmoid tumors. In the third quarter, we generated $49.3 million in net product revenue, representing a 23% growth over the second quarter. We've seen strong adoption of OGSIVEO in newly diagnosed patients and in those seeking their next line of therapy after unsatisfactory outcomes with previous interventions. We're also seeing continued depth of prescribing amongst physicians at centers of excellence and an increase in prescribing amongst the community physicians.

謝謝你，Saqib。推出近一年後，OGSIVEO 持續鞏固並擴大其作為成人纖維瘤最常使用全身性治療藥物的領導地位。第三季度，我們創造了4,930萬美元的淨產品收入，較第二季度成長23%。我們看到，新診斷的患者和先前幹預結果不滿意而尋求下一輪治療的患者廣泛採用了 OGSIVEO。我們也看到卓越中心醫生的處方不斷深入，社區醫生的處方不斷增加。

As we expected, the month of July was a transition period as patients switched to the 150- and 100-milligram blister packs, which were developed to enhance the patient experience and improve adherence. While the transition to this new product form caused some short-term delays due to the need for a new prescription for some patients, the transition is now largely complete, and we expect to see the positive benefits of the blister packs in the coming quarters, including the impact of flat pricing across doses.

正如我們所預料的那樣，七月份是一個過渡期，患者開始使用 150 毫克和 100 毫克的泡罩包裝，這種包裝旨在增強患者體驗並提高依從性。雖然由於某些患者需要新的處方，因此向這種新產品形式的過渡造成了一些短期延遲，但過渡現已基本完成，我們預計將在未來幾個季度看到泡罩包裝的積極效益，包括不同劑量統一定價的影響。

In addition, and as is common with many therapies, we experienced some summer seasonality that impacted new patient starts in July. However, we were pleased to see strong demand return in August and September, with each month successively representing our best performance since launch.

此外，與許多療法一樣，我們經歷了一些夏季季節性變化，影響了 7 月新患者的開始治療。然而，我們很高興看到8月和9月需求強勁回升，每個月都連續呈現出自推出以來的最佳表現。

Importantly, OGSIVEO is providing meaningful clinical benefit in the real-world setting that are consistent with the robust data in our FDA-approved label, and we are seeing limited discontinuations, which we expect will be further supported by the new long-term data from DeFi, which show that with longer-term use, patients are experiencing further reduction in tumor size and sustained symptomatic relief contributing to their overall improved quality of life and desire to stay on therapy. These positive treatment experiences, combined with our focused commercial execution and real-time patient identification efforts, make us confident that we are well positioned for continued growth in the fourth quarter and beyond.

重要的是，OGSIVEO 在現實世界中提供了有意義的臨床益處，這與我們 FDA 批准標籤中的可靠數據一致，並且我們看到停藥的情況有限，我們預計 DeFi 的新長期數據將進一步支持這一點，這些數據表明，隨著長期使用，患者的腫瘤大小進一步縮小，症狀持續緩解，從而有助於改善他們整體的生活質量和繼續接受治療的願望。這些積極的治療體驗，加上我們專注的商業執行和即時患者識別工作，使我們相信，我們已做好準備，在第四季度及以後繼續實現成長。

As we approach the one-year mark in our launch, we're now in a position to share some learnings and metrics from the past year, all of which increased our understanding of key prescribing and patient dynamics and underscores our confidence in the magnitude of the commercial opportunity. First, I'll touch on the patient population. In September, over 800 unique patients filled a prescription for OGSIVEO.

隨著我們推出該產品即將迎來一周年，我們現在可以分享過去一年的一些經驗和指標，所有這些都增加了我們對關鍵處方和患者動態的理解，並強調了我們對商業機會規模的信心。首先，我想談談患者族群。9 月份，超過 800 名患者開出了 OGSIVEO 處方。

As you might recall, we've observed median durations of treatment between 3 and 4.5 years in our clinical trials. While it's still too early to know what our median treatment duration will be in the real-world setting, we are pleased by the low rates of discontinuation we are seeing thus far and believe that the new long-term follow-up data from DeFi will support extended treatment durations and enable patients to continue receiving the life-changing benefits of our medicine.

您可能還記得，我們​​在臨床試驗中觀察到治療的平均持續時間為 3 至 4.5 年。雖然現在還無法知道在現實世界中我們的平均治療持續時間是多少，但我們對迄今為止看到的低停藥率感到高興，並相信來自 DeFi 的新長期隨訪數據將支持延長治療時間並使患者能夠繼續接受我們藥物改變生活的好處。

Now it's important to note that the number of patients filling a script in any given month underrepresents the total number of actively treated patients since not all of them refill exactly on time. The introduction of the blister packs gives us greater visibility into dosing and administration patterns. And given their flat pricing, the blister packs also allow us to capture commensurate value at the dose best suited for each patient.

現在值得注意的是，任何一個月內開立處方的患者數量都低於接受積極治療的患者總數，因為並不是所有的患者都按時續藥。泡罩包裝的引入使我們更加了解劑量和給藥模式。由於泡罩包裝採用固定定價，我們也能以最適合每位患者的劑量獲取相應的價值。

We're already seeing the timing and predictability of refills improve with the adoption of the blister packs. As of the end of September, approximately 65% of OGSIVEO patients are on the blister pack and are experiencing the convenience, reduced pill burden and improved compliance that this product format offers. We expect to complete the transition to the blister packs by the end of the year. We're gratified with the increasing number of patients we've had the opportunity to serve, but we believe that we've only scratched the surface, and here's why. Growing use of the desmoid-specific ICD-10 code, which was launched right before our FDA approval in October 2023, has better informed our understanding of the overall market size.

隨著泡罩包裝的採用，我們已經看到補充藥物的時間性和可預測性得到改善。截至九月底，約有 65% 的 OGSIVEO 患者採用泡罩包裝，並體驗到該產品形式帶來的便利性、減少的藥丸負擔和提高的依從性。我們預計在今年年底前完成泡罩包裝的過渡。我們很高興能為越來越多的患者提供服務，但我們認為這只是觸及了表面，原因如下。在我們於 2023 年 10 月獲得 FDA 批准之前推出的針對纖維瘤的 ICD-10 代碼的使用日益廣泛，這讓我們更好地了解了整體市場規模。

Based on our prior analysis, we originally calculated that there were 5,500 to 7,000 desmoid tumor patients under active management each year in the US out of a diagnosed prevalent population of approximately 30,000 patients.

根據我們先前的分析，我們最初計算出，在美國確診的患病人群約 30,000 名中，每年有 5,500 至 7,000 名纖維瘤患者接受積極治療。

Through August of this year, approximately 10,000 unique desmoid tumor patients have already been identified through the new diagnosis code data. This strongly suggests that our earlier estimate of patients under active management was markedly conservative.

截至今年 8 月，已有約 1 萬名獨特的纖維瘤患者透過新的診斷代碼數據得到識別。這強烈表明我們先前對接受積極管理的患者人數的估計明顯保守。

Although not every patient captured by these codes may require active treatment immediately, the transparency afforded by a desmoid tumor-specific code enables our team to reach prescribers as they're making treatment decisions. We also know that these desmoid tumor-specific codes have not yet been fully adopted, as is the case with any new ICD-10 rollout. So we expect these numbers will continue to grow, and we will revise our estimates accordingly in the future.

儘管並非每個被這些代碼捕獲的患者都需要立即接受積極治療，但特定於纖維瘤的代碼所提供的透明度使我們的團隊能夠在處方醫生做出治療決策時與他們取得聯繫。我們也知道，這些針對纖維瘤的特定代碼尚未被完全採用，就像任何新的 ICD-10 推出的情況一樣。因此，我們預計這些數字將繼續增長，並且我們將在未來相應地修改我們的估計。

Moving on to the physician community. As of quarter end, we see in our data that provide us at approximately 420 treatment centers have prescribed OGSIVEO, which is far beyond the approximately 90 Sarcoma Centers of Excellence. Physicians at these centers were our earliest adopters, and OGSIVEO is firmly established as a systemic standard of care therapy for desmoid tumors in these centers.

轉向醫生社區。截至季度末，我們從數據中看到，大約有 420 家治療中心開出了 OGSIVEO，遠遠超出了約 90 家肉瘤卓越中心的數量。這些中心的醫生是我們最早的採用者，OGSIVEO 已牢固確立為這些中心針對纖維瘤的系統性標準治療。

One of our key goals has been to reach physicians and patients outside of these centers, and our strong commercial execution, coupled with high awareness and robust demand, has allowed us to broaden our reach to community physicians. As it stands today, 57% of OGSIVEO prescribers are practicing in the community setting.

我們的主要目標之一是接觸這些中心以外的醫生和患者，我們強大的商業執行力，加上高度的知名度和強勁的需求，使我們能夠擴大到社區醫生的覆蓋範圍。目前，57% 的 OGSIVEO 處方人員在社區環境中行醫。

Lastly, robust and broad payer coverage has been an area of strength since our FDA approval and remains strong with the introduction of the blister packs. When patients are prescribed OGSIVEO, they have been able to access it efficiently due to strong reimbursement.

最後，自 FDA 批准以來，強大而廣泛的付款人覆蓋一直是我們的強項，並且隨著泡罩包裝的推出而保持強勁勢頭。當患者被處方 OGSIVEO 時，由於強大的報銷管道，他們能夠有效地獲得藥物。

Our feedback from physicians started off positive and has only continued to improve. In our market research, we ask physicians how well the treatments they use perform on a number of important attributes. On this chart, you can see that OGSIVEO far outperforms across every attribute, most notably from an efficacy perspective, but also along the dimensions of tolerability, improvements in pain and overall quality of life. The positive feedback on OGSIVEO's profile translates into strong physician intent to prescribe. Specifically from our research, approximately 90% of prescribers surveyed said that they're likely to use OGSIVEO as a frontline treatment.

我們從醫生那裡得到的回饋一開始是正面的，而且不斷改善。在我們的市場調查中，我們詢問醫生他們所使用的治療方法在許多重要屬性上的表現如何。在這張圖表上，您可以看到 OGSIVEO 在各個屬性上都表現優異，最顯著的是從功效的角度來看，而且在耐受性、疼痛改善和整體生活品質等方面也表現出色。OGSIVEO 簡介上的正面回饋意味著醫生有強烈的開處方意願。具體來說，從我們的研究來看，大約 90% 接受調查的處方者表示他們可能會使用 OGSIVEO 作為第一線治療。

Second, our research indicates that nearly all physicians surveyed not only expect to continue using OGSIVEO, about 60% also expect to increase their usage in the coming year. Collectively, this supports the potential for strong growth ahead.

其次，我們的研究表明，幾乎所有受訪的醫生不僅希望繼續使用 OGSIVEO，約 60% 的醫生還希望在來年增加使用量。總體而言，這支持了未來強勁成長的潛力。

I would now like to share some evolving treatment dynamics that further underpin our confidence in the desmoid tumor opportunity, starting with overall attitudes towards how and when to intervene for patients with desmoid tumors, which point to the urgency to treat at the earliest sign of progression.

現在，我想分享一些不斷發展的治療動態，以進一步增強我們對纖維瘤治療機會的信心，首先是對於如何以及何時對纖維瘤患者進行幹預的總體態度，這些態度表明在出現進展的最早跡象時進行治療至關重要。

We're seeing increasing levels of alignment with guideline-based treatment, which favors systemic therapy over surgery for patients who require active treatment. However, more recently, we have also observed a growing emphasis on prescribers initiating treatment based on a range of clinical symptoms of progression, not only radiographic evidence of progression. In fact, 87% of physicians surveyed indicated likelihood to use OGSIVEO for symptomatic patients without radiographic progression.

我們看到，基於指引的治療越來越受到重視，對於需要積極治療的患者，系統治療比手術更受青睞。然而，最近我們也觀察到，醫生越來越重視根據病情進展的一系列臨床症狀來開始治療，而不僅僅是根據病情進展的放射學證據。事實上，87% 受訪的醫生表示可能會對有症狀且無放射學進展的患者使用 OGSIVEO。

As shown on this slide, 67% of doctors view new or worsening pain, 75% view worsening symptoms overall and 51% considered decline in function as factors for initiating treatment. Each of these responses is higher than what we saw at this time last year, and we expect that the sentiment will continue to grow amongst the treating community and drive urgency to treat.

如本投影片所示，67% 的醫生認為新的或惡化的疼痛、75% 的醫生認為整體症狀惡化、51% 的醫生認為功能下降是開始治療的因素。每個反應都比我們去年此時看到的要高，我們預計這種情緒將在治療界中繼續增長，並推動治療的緊迫性。

As a reminder, OGSIVEO's label covers treatment based on either symptomatic or radiographic progression. So with these shifting treatment landscape dynamics, we expect that more patients will become candidates for OGSIVEO earlier in the course of their disease.

提醒一下，OGSIVEO 的標籤涵蓋基於症狀或放射學進展的治療。因此，隨著治療格局的不斷變化，我們預計更多的患者將在疾病早期成為 OGSIVEO 治療的候選人。

We also continue to make important progress to bring OGSIVEO to patients outside the US. In the EU, our marketing authorization application is currently under review, and we anticipate approval in the first half of next year. Our plan for the EU launch is to begin with Germany and then expand to other countries.

我們也持續取得重要進展，將 OGSIVEO 帶給美國以外的患者。在歐盟，我們的行銷授權申請目前正在審查中，預計明年上半年將獲得批准。我們在歐盟推出的計畫是從德國開始，然後擴展到其他國家。

To support these efforts, we've established European headquarters in Switzerland and hired commercial and medical leadership as well as medical science liaisons with other key personnel and field team members in the process of being onboarded. We're also conducting comprehensive pricing and market access work in each of these key European markets to facilitate a successful series of launches. The European market represents an attractive opportunity for us, with a proportionate number of desmoid tumor patients to that in the US. We see a number of characteristics that are conducive to a successful launch. First, prescribers recognize the high unmet need with available treatment options, which are limited, given that there are currently no EMA-approved therapies and access to off-label treatments is not broad.

為了支持這些努力，我們在瑞士設立了歐洲總部，並聘請了商業和醫療領導以及醫學科學聯絡員以及其他正在入職的關鍵人員和現場團隊成員。我們也在每個主要的歐洲市場開展全面的定價和市場准入工作，以促進一系列產品的成功發布。歐洲市場對我們來說是一個相當吸引人的機會，因為這裡的纖維瘤患者數量與美國相當。我們看到了許多有利於成功發布的特徵。首先，由於目前尚無 EMA 批准的療法，且非說明書用途治療的可及性不強，處方人員認識到現有治療方案有限，存在很大的未滿足需求。

Further, while surgery is considered for some patients, it is selected less frequently for the treatment of desmoid tumors in some European countries.

此外，雖然有些患者會考慮手術，但在某些歐洲國家，手術治療纖維瘤的情況較少。

Our survey work indicates high enthusiasm for the potential approval of OGSIVEO. Based on a blinded profile, more than 90% of oncologists are likely to prescribe and believe that OGSIVEO offers clinical benefits not offered by other therapies.

我們的調查工作表明，人們對 OGSIVEO 的潛在批准熱情很高。根據盲法分析，超過 90% 的腫瘤學家可能會開處方並相信 OGSIVEO 具有其他療法無法提供的臨床益處。

Importantly, several key opinion leaders and sites already have experience with OGSIVEO through DeFi as well as through our compassionate use program, which is more than 250 active patients. And finally, the care of desmoid tumors is relatively centralized in Europe, enabling the use of an efficient commercial footprint.

重要的是，幾位關鍵意見領袖和網站已經透過 DeFi 以及我們的同情使用計劃使用 OGSIVEO，該計劃有超過 250 名活躍患者。最後，纖維瘤的治療相對集中在歐洲，從而能夠利用高效的商業足跡。

Turning briefly to Japan. We've had several successful discussions with the PMDA over the course of the preceding months, and we expect to initiate a bridging study next year. We are very pleased with the commercial performance of OGSIVEO to date in the US and are confident in the significant opportunity for growth ahead of us on a global basis.

簡要談談日本。在過去的幾個月裡，我們與 PMDA 進行了幾次成功的討論，我們預計明年啟動一項橋接研究。我們對 OGSIVEO 迄今為止在美國的商業表現感到非常滿意，並對我們在全球範圍內未來巨大的成長機會充滿信心。

To recap just a few of the tailwinds supporting continued strong growth, there is a large and growing patient population, which is larger than our original estimates, and increasing propensity to treat with systemics based on treatment guidelines, a shift towards initiating treatment based on symptoms rather than radiographic criteria, strong physician preference for OGSIVEO across efficacy, safety and quality of life metrics as well as long-term data that support durable benefits with continued use of OGSIVEO. We are gratified that OGSIVEO is changing the lives of patients with desmoid tumors and look forward to serving many more patients in the months and years ahead.

回顧一下支持持續強勁增長的幾個有利因素，患者數量龐大且不斷增長，超過了我們最初的估計，並且越來越傾向於根據治療指南進行系統治療，轉向根據症狀而不是放射學標準開始治療，醫生在療效、安全性和生活質量指標方面強烈偏好 OGSIVEO，長期數據也支持繼續使用 OGSIVEO 帶來持久的益處。我們很高興看到 OGSIVEO 改變了患有纖維瘤的患者的生活，並期待在未來的歲月裡為更多的患者提供服務。

Turning now to mirdametinib. We are very excited about the significant opportunity ahead of us to make a profound impact on lives of patients and families living with this chronic and highly debilitating disease. There are approximately 100,000 people in the United States living with NF1. These individuals have a 30% to 50% lifetime risk of developing plexiform neurofibromas, which are tumors that grow along peripheral nerve sheets and can cause severe disfigurement, pain and functional impairment.

現在來談談 mirdametinib。我們對眼前這個重大機會感到非常興奮，我們將為患有這種慢性和高度衰弱性疾病的患者和家庭的生活帶來深遠的影響。美國約有 10 萬人患有 NF1。這些人一生中罹患叢狀神經纖維瘤的風險為 30% 至 50%，這種腫瘤沿著週邊神經片生長，可導致嚴重毀容、疼痛和功能障礙。

We estimate that there are approximately 40,000 patients with NF1-PN in the US today, 75% of whom are adults who currently do not have an FDA-approved therapy. As there is no specific demographic leaning for this disease, we estimate that there are a proportionate number of people living with NF1-PN outside of the United States as well.

我們估計，目前美國約有 4 萬名 NF1-PN 患者，其中 75% 是目前尚未接受 FDA 核准治療的成年人。由於這種疾病沒有特定的人口統計傾向，我們估計在美國以外也有一定比例的人群患有 NF1-PN。

While MEK inhibitors have emerged as a validated class of treatment for NF1-PN, there is currently no standard of care, no formal treatment guidelines and a highly fragmented treatment landscape with significant use of off-label therapies, even for pediatric patients for whom there is an approved medicine. Our market research shows that only a small portion of NF1 patients have been treated with a targeted therapy and that this community is desperately in need of new options.

儘管 MEK 抑制劑已成為治療 NF1-PN 的有效方法，但目前尚無標準治療方法和正式治療指南，治療格局高度分散，大量使用非說明書療法，即使對於已有核准藥物的兒科患者也是如此。我們的市場調查顯示，只有一小部分NF1患者接受了針對性治療，而這個族群迫切需要新的選擇。

Data from our Phase 2b ReNeu trial support mirdametinib's potential to be a differentiated therapy for both adults and children with NF1-PN. The ReNeu trial results that were presented at ASCO this year and the additional data that will be presented in a few weeks at the Society of Neuro-Oncology meeting, which Jim will share in a few moments, emphasize robust efficacy across both the adult and pediatric cohorts. These results show not only significant reductions in the size of PN tumors, with robust objective response rates confirmed by blinded independent central review, but also very deep responses, which we believe represent an important differentiator for us.

我們的 2b 期 ReNeu 試驗數據支持 mirdametinib 成為針對成人和兒童 NF1-PN 患者的差異化治療方法的潛力。今年在 ASCO 上公佈的 ReNeu 試驗結果以及幾週後在神經腫瘤學會會議上公佈的更多數據（Jim 稍後將分享這些數據）強調了該療法在成人和兒童群體中均具有強大的療效。這些結果不僅表明 PN 腫瘤的尺寸顯著減小，並且具有透過盲法獨立中央審查確認的穩健的客觀反應率，而且反應非常深度，我們認為這對我們來說是一個重要的區別因素。

In addition, both adults and children experienced early and sustained improvements in health-related quality of life over their course treatment with mirdametinib, including clinically significant reductions in pain. These outcomes are very meaningful since, in many cases, the primary goal of treatment is to improve pain and other PN-associated morbidities.

此外，成人和兒童在接受 mirdametinib 治療的過程中，健康相關生活品質均得到了早期和持續的改善，包括臨床上疼痛的顯著減輕。這些結果非常有意義，因為在許多情況下，治療的主要目標是改善疼痛和其他 PN 相關疾病。

Mirdametinib also demonstrated a manageable safety profile in both children and adults, with low rates of Grade 3 related adverse events and low discontinuation rates due to AEs. We believe mirdametinib's tolerability profile supports the potential for extended treatment durations, which is important in a chronic disease like NF1-PN, where there are high rates of recurrence after stopping therapy.

Mirdametinib 也顯示對兒童和成人均具有可控制的安全性，3 級相關不良事件發生率低，因不良事件導致的停藥率低。我們相信，mirdametinib 的耐受性特徵支持延長治療時間的潛力，這對於像 NF1-PN 這樣的慢性疾病來說很重要，因為停止治療後復發率很高。

Lastly, we believe that mirdametinib's convenient dosing regimen, which provides a built-in treatment holiday and a pediatric-friendly dispersible tablet for oral suspension could further optimize the patient experience and potentially enhance compliance. With our NDA accepted under priority review and our marketing authorization application validated by the EMA, we are moving full steam ahead with commercial preparations.

最後，我們相信，mirdametinib 方便的給藥方案，提供內建的治療假期和適合兒科的口服混懸液分散片，可以進一步優化患者體驗並可能提高依從性。隨著我們的 NDA 獲得優先審查並被 EMA 批准上市授權申請，我們正在全力推進商業化準備。

We are leveraging our commercial infrastructure and learnings from the successful OGSIVEO launch to serve patients with NF1-PN. We've spent the past several years collecting important insights from treating physicians and working to thoroughly understand the needs of the NF1-PN patient and caregiver community. These efforts have been especially critical on behalf of adult patients who have had to face this devastating disease without an approved therapy.

我們正在利用我們的商業基礎設施和從 OGSIVEO 成功發布中獲得的經驗為 NF1-PN 患者提供服務。過去幾年來，我們一直在收集治療醫生的重要見解，並努力徹底了解 NF1-PN 患者和照護者群體的需求。這些努力對於那些不得不面對這種沒有得到批准的治療方法的毀滅性疾病的成年患者來說尤其重要。

Our disease state education campaign, entitled Coping Isn't Care, focuses on educating and empowering young adult patients to advocate for themselves and to engage in ongoing treatment. This campaign has received high engagement and positive feedback from patients and physicians alike.

我們的疾病狀態教育活動名為“應對不是護理”，旨在教育和鼓勵年輕成年患者為自己爭取權益並參與持續治療。本次活動得到了患者和醫生的高度參與和積極回饋。

We've also developed a launch plan that focuses on the aspects that differentiate mirdametinib from other systemic treatments based on our robust efficacy and safety data in patients of all ages. As we did for those with desmoid tumors, we will offer comprehensive patient services through our SpringWorks CareConnections program, which is designed to support the unique needs of patients with NF1-PN and ensure that eligible patients have access to therapy.

我們還制定了一項上市計劃，該計劃基於我們在各個年齡段患者中提供的強大的療效和安全性數據，重點關注將 mirdametinib 與其他全身性治療區分開來的方面。正如我們為患有纖維瘤的患者所做的那樣，我們將透過 SpringWorks CareConnections 計劃提供全面的患者服務，該計劃旨在支持 NF1-PN 患者的獨特需求並確保符合條件的患者能夠接受治療。

We've also hired and started training our sales team, which consists of 35 field representatives. Their initial focus will be on the 70-or-so NF clinical network centers across the United States, many of which have experience with mirdametinib from our ReNeu trial as well as other key treatment sites in both the academic and community setting. These teams will be equipped with comprehensive resources and data to assist with patient identification and enable them to target physicians who are currently managing patients with NF1-PN.

我們還僱用並開始培訓我們的銷售團隊，該團隊由 35 名現場代表組成。他們最初的重點將放在美國各地 70 多個 NF 臨床網路中心，其中許多中心在我們的 ReNeu 試驗中擁有使用 mirdametinib 的經驗，並且在學術和社區環境中的其他關鍵治療場所也有經驗。這些團隊將配備全面的資源和數據，以協助識別患者，並使他們能夠找到目前正在管理 NF1-PN 患者的醫生。

We are incredibly excited by the opportunity ahead of us to serve NF1-PN patients, and we will share more on our commercial plans as we get closer to our February 28 PDUFA date. With that, I'll turn the call over to Jim to discuss recent data highlights and provide an update on our emerging pipeline programs. Jim?

我們對為 NF1-PN 患者服務的機會感到非常興奮，隨著 2 月 28 日 PDUFA 日期的臨近，我們將分享更多有關我們的商業計劃的資訊。說完這些，我將把電話轉給吉姆，討論最近的數據亮點，並提供有關我們新興管道計劃的最新資訊。吉姆？

Thank you, Bhavesh. I am pleased to take you through some of our recent data and important updates on our pipeline programs.

謝謝你，Bhavesh。我很高興向大家介紹我們的一些最新數據和管道計劃的重要更新。

Starting with nirogacestat, long-term follow-up data from our Phase 3 DeFi trial will be presented in our late-breaking oral session at the Connective Tissue Oncology Society this weekend. These results, utilizing an August 2024 data cutoff and with a median duration of therapy of approximately three years, showed that longer-term treatment with nirogacestat was associated with further reductions in tumor size, an increase in the objective response rate with additional partial responses and complete responses, sustained improvements in desmoid tumor symptoms, including pain, and a consistent safety profile compared to the April 2022 data cut utilized for the primary results of the trial. Given the debilitating and chronic nature of desmoid tumors, these results are very important for clinicians and patients as they provide valuable insights on the longer-term use of our medicine.

從 nirogacestat 開始，我們將於本週末在結締組織腫瘤學會的最新口頭會議上公佈第 3 階段 DeFi 試驗的長期追蹤數據。這些結果採用了 2024 年 8 月的數據截止時間，中位治療時間約為 3 年，結果表明，與試驗主要結果所採用的 2022 年 4 月的數據截止時間相比，長期使用 nirogacestat 治療可進一步縮小腫瘤大小，提高客觀反應率並出現額外的部分反應和完全反應，持續改善疼痛的安全性並具有一致的安全性）並具有一致的安全性疼痛。鑑於纖維瘤的殘疾和慢性性質，這些結果對臨床醫生和患者非常重要，因為它們為我們藥物的長期使用提供了寶貴的見解。

Other DeFi data to be presented at CTOS include an oral presentation of a post-hoc analysis assessing the effect of nirogacestat in subgroups of patients with desmoid tumors who have risk factors associated with poor prognosis and a poster on patients with beta-catenin and APC mutations. We are very pleased that the growing evidence from DeFi continues to support the significant benefit that OGSIVEO can provide for a broad range of patients with desmoid tumors.

CTOS 上將展示的其他 DeFi 數據包括事後分析的口頭報告，該分析評估了 nirogacestat 對具有與不良預後相關的風險因素的纖維瘤患者亞群的影響，以及一張關於 β-catenin 和 APC 突變患者的海報。我們非常高興，來自 DeFi 的越來越多的證據繼續支持 OGSIVEO 可以為廣大患有纖維瘤的患者提供顯著的益處。

Turning to mirdametinib, we are pleased that our Phase 2b ReNeu trial was recently published in the Journal of Clinical Oncology, and that new data from ReNeu will be presented at the upcoming Society for Neuro-Oncology meeting. The first data set being presented at SNO is a review of patients achieving deep responses on mirdametinib.

談到 mirdametinib，我們很高興我們的 2b 期 ReNeu 試驗最近發表在《臨床腫瘤學雜誌》上，並且 ReNeu 的新數據將在即將舉行的神經腫瘤學會會議上公佈。SNO 上展示的第一個資料集是對使用 mirdametinib 獲得深度反應的患者的回顧。

We observed impressive depth of response in ReNeu for both children and adults, which was confirmed by blinded independent central review. Depth of response is acknowledged by many clinicians and patients to be an important indicator of treatment success, especially when the tumor is in a critical sight like the head and neck region.

我們觀察到 ReNeu 對兒童和成人的反應深度令人印象深刻，這得到了盲法獨立中央審查的證實。許多臨床醫師和患者認為反應深度是治療成功的重要指標，尤其是當腫瘤位於頭頸部等關鍵部位時。

As highlighted in our abstract, 62% of adults and 52% of children who achieved an objective response -- had a deep response, which we defined as a greater than 50% reduction in tumor volume from baseline. Patients who had a deep response were on treatment longer than those who did not. And importantly, our data identified no baseline characteristics that predict which patients will achieve a deep response, suggesting that the ability of a patient to stay on therapy is an important factor. We believe that mirdametinib, with its differentiated tolerability profile and tablet for oral suspension formulation offers patients a meaningful chance to achieve long-term disease control, tumor shrinkage and symptomatic improvement.

正如我們在摘要中所強調的，62% 的成人和 52% 的兒童獲得了客觀反應——深度反應，我們將其定義為腫瘤體積相對於基線減少 50% 以上。反應強烈的患者接受治療的時間比反應不強烈的患者長。而且重要的是，我們的數據沒有確定可以預測哪些患者將獲得深度反應的基線特徵，這表明患者堅持治療的能力是一個重要因素。我們相信，mirdametinib 憑藉其差異化的耐受性特徵和口服混懸劑型片劑，為患者提供了實現長期疾病控制、腫瘤縮小和症狀改善的重要機會。

Also to be presented at SNO is an analysis of patient health-related quality of life on mirdametinib. Patients with NF1-PN have significant morbidities, which include pain and other symptoms that negatively impact quality of life. Addressing these symptoms is an important goal of treatment.

SNO 上也將展示對 mirdametinib 患者健康相關生活品質的分析。NF1-PN 患者有嚴重的病症，包括疼痛和其他對生活品質有負面影響的症狀。解決這些症狀是治療的重要目標。

In the ReNeu trial, patients on mirdametinib experience clinically-meaningful improvements in their health related to quality of life, which emerged early and sustained during the course of treatment. Nearly half of the base achieved clinically meaningful improvements at Cycle 13, which was the prespecified analysis point. And improvements were noted in subscales, measuring patients' physical, emotional and social experience as well.

在 ReNeu 試驗中，使用 mirdametinib 的患者在生活品質相關的健康狀況方面經歷了具有臨床意義的改善，這種改善在治療過程中早期就出現了，並且持續存在。近一半的基底在第 13 個週期（即預先指定的分析點）實現了具有臨床意義的改善。此外，衡量患者身體、情緒和社會體驗的分量表也得到了明顯改善。

Next, I will cover a few highlights from our earlier state programs and collaborations. Beyond desmoid tumors, nirogacestat is being studied as a monotherapy in a Phase 2 trial in patients with ovarian granulosa cell tumors. We now expect the top line data from this trial to be released in the first half of 2025.

接下來，我將介紹我們早期國家計劃和合作的一些亮點。除了纖維瘤以外，nirogacestat 還在卵巢顆粒細胞瘤患者的 2 期試驗中作為單一療法進行研究。我們目前預計該試驗的頂線數據將於 2025 年上半年發布。

The Phase 2 St. Jude-sponsored study of mirdametinib in children and young adults with low-grade glioma is ongoing. Exciting data from 23 patients enrolled in this study will be presented in an oral presentation at SNO and suggests promising clinical activity in patients with recurrent or progressive low-grade glioma across a variety of MAPK pathway aberrations.

由聖猶達兒童研究醫院贊助的針對患有低度膠質瘤的兒童和年輕人的 mirdametinib 第二階段研究正在進行中。參與這項研究的 23 名患者的令人興奮的數據將在 SNO 的口頭報告中呈現，並表明在多種 MAPK 通路異常的複發性或進行性低級別膠質瘤患者中具有良好的臨床活性。

Our combination studies of mirdametinib with brimarafenib and lifirafenib are also ongoing, and the next set of data from the monotherapy trial of brimarafenib in patients with MAPK operations is on track for release in the second half of 2025.

我們對 mirdametinib 與 brimarafenib 和 lifirafenib 的聯合研究也在進行中，下一組針對 MAPK 手術患者的 brimarafenib 單藥治療試驗數據預計將於 2025 年下半年發布。

Lastly, the Phase 1 trial of SW-682 in patients with Hippo-mutant tumors is underway, with dose escalation currently ongoing. At the recent triple meeting held in Barcelona, we presented two preclinical data sets, elaborating on the potential of SW-682 as well as a monotherapy and in combination with mirdametinib in patients with head and neck cancer and also as a combination partner with KRAS G12C inhibitors in patients with non-small cell lung cancer.

最後，SW-682 對 Hippo 突變型腫瘤患者進行的 1 期試驗正在進行中，目前正在進行劑量遞增。在最近於巴塞隆納舉行的三方會議上，我們展示了兩組臨床前數據集，詳細闡述了 SW-682 作為單一療法和與 mirdametinib 聯合治療頭頸癌患者的潛力，以及作為與 KRAS G12C 抑製劑聯合治療非小細胞肺癌患者的潛力。

Now I'll turn it over to Frank to discuss our final results. Frank?

現在我將把話題交給弗蘭克來討論我們的最終結果。坦率？

Thank you, Jim. I'll now summarize a few highlights from our third quarter 2024 financial results. Starting with revenues. We recorded $49.3 million of OGSIVEO net product revenue in the third quarter. This brings our 2024 year-to-date OGSIVEO net product revenue to $110.5 million.

謝謝你，吉姆。現在，我將總結我們 2024 年第三季財務業績的一些亮點。從收入開始。我們在第三季記錄了 4,930 萬美元的 OGSIVEO 淨產品收入。這使得我們 2024 年迄今的 OGSIVEO 淨產品收入達到 1.105 億美元。

Our total operating expenses increased compared to the third quarter of 2023, driven by the commercial activities to support the US launch of OGSIVEO and the anticipated US launch of mirdametinib. We have a strong balance sheet with $498 million in cash, cash equivalents and marketable securities as of the end of the third quarter.

我們的總營運費用與 2023 年第三季相比有所增加，這主要得益於支持 OGSIVEO 在美國上市以及 mirdametinib 預期在美國上市的商業活動。截至第三季末，我們的資產負債表強勁，現金、現金等價物和有價證券達 4.98 億美元。

We believe our balance sheet will be sufficient to fully fund our operations through profitability, an important milestone, which we expect to achieve in the first half of 2026. Lastly, we have a durable operating plan designed to fund multiple global product launches and to enable the continued investment and expansion opportunities across our pipeline.

我們相信，我們的資產負債表將足以透過獲利為我們的營運提供足夠的資金，這是一個重要的里程碑，我們預計將在 2026 年上半年實現這一目標。最後，我們有一個持久的營運計劃，旨在資助多個全球產品的發布，並確保我們的產品線有持續的投資和擴張機會。

With that, I'll hand the call back over to Saqib.

說完這些，我會把電話轉回給薩奇布。

Thank you, Frank. We are very pleased with our accomplishments to date and have several important milestones ahead of us. The long-term follow-up data from our DeFi trial being presented at CTOS are highly supportive of the benefits of extended treatment durations with OGSIVEO in desmoid tumors. And we believe the data from our ReNeu trial being presented at SNO reinforce the differentiated profile of mirdametinib for patients with NF1-PN. Looking ahead, we have multiple readouts in our emerging portfolio expected in the first half of 2025 as well, and are continuing to advance our early-stage discovery programs.

謝謝你，弗蘭克。我們對迄今為止所取得的成就感到非常高興，並且面前還有幾個重要的里程碑。我們在 CTOS 上展示的 DeFi 試驗的長期追蹤數據強烈支持使用 OGSIVEO 延長治療纖維瘤時間的益處。我們相信，在 SNO 上展示的 ReNeu 試驗數據強化了 mirdametinib 對 NF1-PN 患者的差異化優勢。展望未來，我們預計在 2025 年上半年我們的新興投資組合中也會有多個讀數，並且我們正在繼續推進我們的早期發現計劃。

To close, we are very pleased that OGSIVEO has rapidly become the standard of care for adults with desmoid tumors. As we discussed this morning, there is a large and growing population of desmoid tumor patients in need of the transformative benefits that OGSIVEO offers. And our performance to date represents exceptional progress in terms of market uptake, patient-focused product innovation, physician experience and data supporting long-term use for OGSIVEO and evolving treatment preferences that highlight the growing importance of earlier intervention and systemic therapies for this disease.

最後，我們非常高興 OGSIVEO 已迅速成為成人纖維瘤的治療標準。正如我們今天早上所討論的，越來越多的纖維瘤患者需要 OGSIVEO 提供的變革性益處。我們迄今為止的表現在市場吸收、以患者為中心的產品創新、醫生經驗和支持長期使用 OGSIVEO 的數據以及不斷變化的治療偏好方面取得了非凡的進步，這些都凸顯了早期幹預和全身治療對這種疾病日益增長的重要性。

We have strong conviction that we are just getting started in serving this community in the United States and have a significant opportunity on a global basis as well. We are working with urgency to bring mirdametinib to children and adults with NF1-PN in the US, following our PDUFA date of February 28, and have begun our expansion to serve patients in Europe starting next year.

我們堅信，我們才剛開始為美國的這個社區提供服務，並且在全球範圍內也擁有巨大的機會。根據 2 月 28 日的 PDUFA 日期，我們正在緊急努力將 mirdametinib 帶給美國的 NF1-PN 兒童和成人，並且已開始將服務範圍擴大到從明年開始的歐洲患者。

In parallel, we are advancing our emerging portfolio to serve additional patients living with devastating diseases. We are confident that our strong foundation will support our continued success as we deliver on our mission to make a profound impact on patients' lives.

同時，我們正在推動我們的新興產品組合，為更多患有毀滅性疾病的患者提供服務。我們堅信，我們堅實的基礎將支持我們繼續取得成功，履行我們的使命，為患者的生活帶來深遠的影響。

As always, I would like to thank the patients and investigators who participate in our clinical trials, our patient advocacy partners and collaborators and our team of SpringWorkers working on behalf of patients in multiple community settings. We are now happy to take questions. Operator?

像往常一樣，我要感謝參與我們臨床試驗的患者和研究人員、我們的患者權益夥伴和合作者以及在多個社區環境中代表患者工作的 SpringWorkers 團隊。我們現在很樂意回答問題。操作員？

(Operator Instructions) Anupam Rama, JPMorgan.

(操作員指示) Anupam Rama，摩根大通。

Could you give us a little bit more color on how the blister pack transitions progressed over 3Q and how we should think about sort of that remaining 35% progressing through 4Q? I'm just trying to understand what have been the biggest sort of challenges to this transition and how you guys have been working through those and getting around some of the challenges.

您能否向我們詳細介紹第三季泡罩包裝轉型的進展情況，以及我們應該如何看待剩下的 35% 在第四季的進展？我只是想要了解這種轉變過程中最大的挑戰是什麼，以及你們是如何克服和處理這些挑戰的。

Thanks, Anupam. So listen, we made the choice to make the transition this quarter, knowing that it was going to pose some challenges over the course of the quarter, and we're very happy with where we've come out. And so what it means -- what it meant over the course of the quarter is we saw about a two-week delay for many patients in getting their prescriptions refilled as they transitioned from bottle to blister pack refills.

謝謝，Anupam。所以聽著，我們選擇在本季進行轉型，知道這將在本季帶來一些挑戰，但我們對目前的結果感到非常滿意。這意味著——在本季度，我們發現許多患者在從瓶裝藥物過渡到泡罩包裝藥物時，大約需要兩週的時間才能獲得續藥。

And so over the course of that time, we saw the impact of that largely in July. We finished, as we've said on the call, with our strongest month ever in August and an even stronger month in September. And I think it positions us really well.

因此，在這段時間裡，我們在 7 月主要看到了其影響。正如我們在電話會議上所說的那樣，八月是我們有史以來表現最強勁的月份，九月的表現甚至更加強勁。我認為這對我們非常有利。

Now the reason we made this transition, quite frankly, for patients, it's a reduced pill burden. It tends to result in improved compliance and adherence and improved convenience for those patients. For SpringWorks, it improves our tracking of dose reductions, and we've got flat pricing between 100 milligrams and 150 milligrams. And so where that positions us going forward is to accelerate. And that's what we're seeing over the course of the third quarter.

坦白說，我們進行這種轉變的原因是為了減輕患者的藥物負擔。它往往會提高患者的依從性和堅持性，並為患者帶來更多便利。對於 SpringWorks，它改進了我們對劑量減少的跟踪，並且我們在 100 毫克和 150 毫克之間獲得了統一的定價。因此，我們前進的方向就是加速。這就是我們在第三季看到的情況。

That's what we expect to see going forward.

這正是我們期望看到的未來​​。

And I think that as you've mentioned, Anupam, we're 2/3 through that transition, with the bulk of the patients who actually were going to benefit from that transition in the third quarter and obviously, well through that now and expect to be through it by the end of the year.

我認為，正如您所提到的，Anupam，我們已經完成了這一轉變過程的 2/3，大多數患者實際上將在第三季度從這一轉變中受益，顯然，他們現在已經順利完成了這一轉變，預計到今年年底將會完成。

Yaron Werber, TD Cowen.

Yaron Werber，TD Cowen。

This is Jaena on for Yaron. You mentioned on the call that your ICD-10 data suggests that you've underestimated the desmoid tumor population. Could you elaborate a little bit on this? And specifically, what does your ICD-10 data indicate to you about the size of the overall opportunity in desmoid tumor?

這是 Jaena 代替 Yaron 上場。您在電話中提到，您的 ICD-10 數據顯示您低估了纖維瘤的數量。能進一步詳細說明一下嗎？具體來說，您的 ICD-10 數據告訴您關於纖維瘤的整體機會大小是多少？

Sure. Thank you for the question. So just to level set, right, these 10,000 patients were identified between the introduction of the desmoid tumor-specific ICD-10 codes in October 2023 and August of this year. So just a little under one year. The number is meaningfully higher than the 5,500 to 7,000 patients that we've spoken about in the past.

當然。感謝您的提問。因此，只是為了水平設置，這 10,000 名患者是在 2023 年 10 月和今年 8 月引入針對纖維瘤的 ICD-10 代碼之間確定的。所以還不到一年。這個數字明顯高於我們過去談到的 5,500 至 7,000 名患者。

And we know it's actually an undercount since new codes actually take several years to become fully adopted. Proof of this fact is that in our data, we are seeing many desmoid tumor patients being prescribed OGSIVEO that are still being coded on the old code, which is for the general soft tissue neoplasms D48.1 ICD-10 code. And for a chronic and debilitating disease like desmoid tumors, it's not a matter of if, but when they will get prescribed on therapy.

我們知道這實際上是一個低估，因為新法規實際上需要幾年才能完全採用。這一事實的證明是，在我們的數據中，我們看到許多被處方 OGSIVEO 的纖維瘤患者仍然使用舊代碼進行編碼，即針對一般軟組織腫瘤的 D48.1 ICD-10 代碼。對於像纖維瘤這種慢性且使人衰弱的疾病，治療不再是是否的問題，而是何時的問題。

Peter Lawson, Barclays.

巴克萊銀行的彼得勞森 (Peter Lawson)。

And just on the -- thanks for the demand dynamics. I wonder if you could kind of dig in a little bit around that. What does demand look like beyond September? And did you see month-over-month growth in Q3? And how does that continue through Q4?

非常感謝您對需求動態的關注。我想知道您是否可以對此進行深入探討。九月以後需求狀況如何？您看到第三季的環比成長了嗎？第四季的情況如何？

Sure. Thank you, Peter. Listen, I think we are -- as we said, we're poised for acceleration from here. And within the quarter, you saw that our largest ever month was August, and then that was superseded by our largest ever month being September within that quarter, adjusting for certainly the decision we made to get -- to do the blister packs with the impact of that in July.

當然。謝謝你，彼得。聽著，我想我們—正如我們所說的，我們已準備好從現在開始加速。在本季度中，您會發現我們有史以來最大的月份是 8 月，然後被我們有史以來最大的月份所取代，即該季度的 9 月，這當然是根據我們在 7 月份做出的決定進行調整的——生產泡罩包裝。

But if we step back, let's think about where we are in this journey to get to the larger group of patients. We already have 800 unique prescriptions in September. We've been steadily adding a consistent number of patients throughout the year with no reduction from where we are now to where we were then. And we're starting to see the benefits of the blister pack, both in the third quarter and then going forward here, right, with parity pricing between the 100-milligram and 150-milligram dose.

但如果我們退一步思考，我們想一想，在接觸更大群體的患者的過程中，我們處於什麼位置。9 月我們已經有 800 張獨特處方。我們全年都在穩定增加患者數量，與以前相比沒有減少。我們開始看到泡罩包裝的好處，無論是在第三季還是未來，100 毫克和 150 毫克劑量之間的價格都是平價。

Add to that the fact that this is a larger addressable market than the one we anticipated and by quite a bit as we think of 10,000 ICD-10 claims already processed within a year, and that we believe is an under account of that patient population going forward. Combine that with the fact that the physician satisfaction is not just very high, but the likelihood to treat is higher and those -- the large majority of those physicians say they expect to be using it more going forward.

此外，事實上，這個潛在市場比我們預期的要大得多，考慮到一年內已經處理了 10,000 份 ICD-10 索賠，我們認為這仍然低估了未來的患者人數。再加上醫生的滿意度不僅非常高，而且治療的可能性也更高，絕大多數醫生表示，他們希望在未來能更多地使用它。

Quite frankly, the question here on the treatment use of OGSIVEO for desmoid tumor patients is not if, but when. As patients need the treatment, we believe they will come to us. If not at the outset, we are certainly seeing them steadily being added to our patient roles over the course of the year.

坦白說，關於使用 OGSIVEO 治療纖維瘤患者的問題不是是否使用，而是何時使用。由於患者需要治療，我們相信他們會來找我們。即使一開始沒有，我們肯定會看到他們在這一年中穩步增加到我們的患者角色。

Now I think the important element to all of this, that not only are we seeing -- it's a bigger patient population, physicians are getting more familiar with the medicine and are much more likelihood to treat. We have patients on the blister pack, which is going to improve refill rates and certainly be pricing neutral to us. But on top of that, we are going to be sharing data at CTOS next weekend showing the benefits of continued treatment.

現在我認為這一切的重要因素是，我們不但看到了——患者人數越來越多，醫生對藥物也越來越熟悉，治療的可能性也越來越大。我們有一些患者使用泡罩包裝，這將提高補充率，並且對我們來說肯定是價格中立的。但除此之外，我們將於下週末在 CTOS 上分享數據，以展示持續治療的好處。

So not only is there kind of the rational benefit of they feel having reduction in pain, but we are seeing continued reduction in tumor size, continued benefits on patient-reported outcome scores, increased complete responses, partial responses from the benefit -- from the data that we have from our open-label extension that's now out to three years. So put that together, we feel great about the fourth quarter, but even well beyond the fourth quarter, Peter, going forward, knowing that we made the conscious decision in the third quarter to set ourselves up for it going forward.

因此，他們不僅感覺到疼痛減輕，而且我們還看到腫瘤大小持續縮小、患者報告結果評分持續改善、完全緩解率增加、部分緩解率提高——從我們開放標籤擴展試驗目前已持續三年的數據來看。綜上所述，我們對第四季度的表現非常滿意，但即使在第四季度之後，彼得，展望未來，我們知道我們在第三季度做出了明智的決定，為未來的發展做好了準備。

Corinne Johnson, Goldman Sachs.

高盛的科琳·約翰遜 (Corinne Johnson)。

Helpful commentary on that last question, Saqib. I'm hoping you could expand a little bit on that. It sounds like all the trends are kind of pointing in the right direction. So is there any reason to expect that trends into October, November, December would reverse what you've seen thus far, which is month-over-month growth every quarter? And can you just help clarify what you're seeing now as we get into this fourth quarter?

對最後一個問題的評論很有幫助，Saqib。我希望您能就這一點稍微展開一下。聽起來所有的趨勢都指向正確的方向。那麼，是否有理由預期 10 月、11 月和 12 月的趨勢會逆轉您迄今為止所看到的趨勢，即每季的環比成長？您能否幫助澄清一下我們目前進入第四季時看到的情況？

Yes. I see nothing here certainly over the long-term trend that does not bode well for us in terms of stacking patients, getting better refill rates, certainly pricing, obviously being set and now getting to people showing that benefit to physicians for longer-term dosing. So the stacking of patients, the acceleration that I see currently and what I expect to see, I don't see any abatement there.

是的。從長期趨勢來看，我在這裡看到的一切都對我們不利，包括堆積患者、獲得更好的補充率、當然還有顯然已經確定的定價，現在人們開始向醫生展示長期用藥的好處。因此，就我目前所看到的以及我預期看到的病人堆積速度而言，我沒有看到任何減緩的跡象。

David Nierengarten, Wedbush Securities.

韋德布希證券公司的 David Nierengarten。

If we could dig into the patients being treated at the moment. Are they -- who come on to OGSIVEO treatment, are they typically active progressors? Are they transitioning from watch and wait to active treatment? Are they switching from other treatments? Maybe if you could dig into that and if that's been changing over summer to include more -- maybe more watchful waiting or vice versa, I don't know, but if you could comment on that, that would be great.

如果我們可以深入了解目前正在治療的患者。接受 OGSIVEO 治療的人是否通常都是積極進展者？他們是否從觀察等待轉向積極治療？他們是否從其他治療方法轉而採用其他治療方法？也許如果您可以深入研究這一點，並且如果這種情況在夏季有所變化，包括更多 - 也許是更多的警惕等待或反之亦然，我不知道，但如果您可以對此發表評論，那就太好了。

No. Thank you for the question. Obviously, we are very pleased with the number of patients we see at the end of September. Specific to your question, we are seeing patients across the treatment continuum in our data, right? We're seeing newly diagnosed patients.

不。感謝您的提問。顯然，我們對九月底接診的病患數量感到非常滿意。具體到您的問題，我們在數據中看到了整個治療過程中的患者，對嗎？我們正在接診新診斷的病人。

We've seen patients who came off of watchful waiting. We're seeing switch patients from TKIs, chemotherapy. And as you've seen from the data we presented also, patients who had surgery have seen regrowth in their tumor. So we've seen a mix across the -- there is no particular leaning towards any specific group.

我們見過一些不再密切觀察的病人。我們看到患者從 TKI 轉為化療。正如您從我們提供的數據中看到的，接受手術的患者的腫瘤已經重新生長。因此，我們看到了混合情況——並沒有特別傾向於任何特定群體。

So David, what I would add to that is kind of what I was saying before is that we really believe it's not a function of if but when with this patient group. And as with most rare diseases, with greater awareness, greater familiarity with the medicine from the prescriber community, we expect to see greater urgency to treat. All of the clinical data, including what we'll share at CTOS actually argues for that. And so what we see, as we've seen in many other situations with rare diseases, you cross that threshold of awareness and you will continue to add patients. And particularly in this disease, patients do go through other treatments before they get to us, and we expect more and more to come to us first.

所以，大衛，我想補充的是，我之前說過，我們確實相信，對於這個患者群體來說，這不是一個是否發生的問題，而是一個何時發生的問題。與大多數罕見疾病一樣，隨著醫生群體對罕見疾病的認識不斷提高、對藥物越來越熟悉，我們預計治療的緊迫性會越來越大。所有臨床數據，包括我們將在 CTOS 上分享的數據實際上都證明了這一點。因此，我們看到，正如我們在許多其他罕見疾病的情況中看到的那樣，一旦跨越了認知的門檻，患者人數就會不斷增加。特別是對於這種疾病，患者在接受我們的治療之前確實會接受其他治療，我們預計越來越多的患者會先接受我們的治療。

Alec Stranahan, Bank of America.

美國銀行的亞歷克·斯特拉納漢（Alec Stranahan）。

Bhavesh mentioned limited OGSIVEO discontinuations to date. Do you have a sense of how prescribers are approaching this? And maybe what the patient profiles were who did discontinue? And as a follow-up, what percentage of patients have had dose reductions? And are maybe drug holidays also being considered for some patients perhaps in the context of ovarian dysfunction?

Bhavesh 提到，迄今為止，OGSIVEO 的停產有限。您是否了解處方人員如何處理這個問題？也許那些停止治療的患者的情況是怎麼樣的？作為後續調查，有多少比例的患者減少了劑量？對於某些卵巢功能障礙的患者，是否也考慮實行藥物假期？

Yes. So I think rate of discontinuations, as I said, have been generally low. And what we'd expect, given the clinical trial experience indicating that patients are having a positive experience on OGSIVEO and they're able to stay on therapy, right? So overall, I think -- I'm trying to recall the other part of the question. We've seen fewer than 10% of patients overall who started OGSIVEO discontinuing a year -- roughly a year into launch at this point in time.

是的。因此我認為，正如我所說，停產率總體上一直很低。而且，根據臨床試驗經驗，我們預期患者對 OGSIVEO 的體驗良好，能夠繼續接受治療，對嗎？所以總的來說，我認為——我正在嘗試回憶問題的另一部分。我們發現，在開始使用 OGSIVEO 一年後，停用該藥物的患者不到 10%——目前大約是推出一年後。

From a dose reduction perspective, we -- with the transparency afforded by the bottles, we did not have full visibility. We're starting to get more visibility with patients switching to the 100- and 150-milligram blister packs. And based on the conversion data we've seen so far, we're seeing a majority of the patients are still on the 150 milligram, which actually portends well from being able to tolerate therapy at the maximum dose. But we do see a proportion of patients at the 100-milligram dose as well. We will get much better transparency into that overall mix by the end of Q4 when the transition is complete.

從減少劑量的角度來看，由於瓶子的透明度，我們無法完全看到它。隨著患者開始使用 100 毫克和 150 毫克泡罩包裝，我們開始獲得更多的可見度。根據我們目前看到的轉換數據，我們發現大多數患者仍服用 150 毫克，這實際上預示著能夠耐受最大劑量的治療。但我們也確實看到一部分患者服用了 100 毫克劑量。到第四季末，當過渡完成時，我們將對整體組合有更好的透明度。

And what I'd say, Alec, is you can use the reference of the DeFi study where you had about 40% of patients by clinical protocol dose reduced down. So as we think of the opportunity for the blister packs going forward, we haven't seen that yet. We'll have greater clarity, as Bhavesh says, with -- once you've got people on the 100-milligram dose. But if that is the amount that goes down, that is the capture that we see possible through the introduction of the blister pack and 100 milligrams. I hope that's --

我想說的是，亞歷克，你可以參考 DeFi 的研究，其中大約 40% 的患者按臨床方案減少了劑量。因此，當我們思考泡罩包裝未來的發展機會時，我們還沒有看到這一點。正如 Bhavesh 所說，一旦人們服用 100 毫克劑量，我們就會更加清楚。但如果數量下降的話，我們認為透過引入泡罩包裝和 100 毫克的劑量就有可能實現這一目標。我希望這是--

Rosy Liao, Guggenheim.

廖淑儀，古根漢。

This is Rosy on for Michael Schmidt. So I guess for OGSIVEO looking forward to 2025, how should we think about the trajectory for the second year of OGSIVEO launch relative to the first year and perhaps the longer-term effects of the new formulation?

這是邁克爾·施密特 (Michael Schmidt) 的 Rosy。因此，我猜對於 2025 年的 OGSIVEO，我們應該如何看待 OGSIVEO 推出的第二年相對於第一年的軌跡，以及新配方的長期影響？

And I guess switching things up a little bit. With respect to mirdametinib with your PDUFA coming up at the end of February, I guess, how should we think about the trajectory there for that launch relative to that of OGSIVEO?

我想，這會稍微改變一些事情。關於 mirdametinib，您的 PDUFA 將於 2 月底出台，我想，我們該如何看待產品相對於 OGSIVEO 的上市軌跡？

So thank you, Rosy. Listen, I think I'll come back to where we are. I think we are positioned incredibly well for 2025 and beyond, right? All of the stage has been set. And let me take you through the parameters once again, right?

所以謝謝你，Rosy。聽著，我想我會回到我們所在的地方。我認為我們為 2025 年及以後做好了非常有利的準備，對嗎？一切舞台都已準備就緒。讓我再帶您了解這些參數，好嗎？

Already, we talked about unique -- 800 unique prescriptions going forward. But what gives us the confidence going forward from here is the fact that it is a larger patient population. We talked about the 10,000-plus ICD-10 claims, which we think is an under call.

我們已經討論了獨特的——未來將有 800 種獨特的處方。但讓我們對未來充滿信心的是，患者人數將會更加龐大。我們討論了超過 10,000 起 ICD-10 索賠，我們認為這是一個低估數字。

Our -- the enthusiasm of physicians with OGSIVEO, we are already the systemic standard of care. And we expect that only to improve with doctors indicating their desire to use it more going forward. We now will be, by the end of the year, as we get into 2025, through the blister pack transition. So you'll be able to benefit from better refill rates, the better compliance for patients who are now required to take fewer pills and certainly, as I said, parity between the 100 and 150-milligram dosing for us.

我們的－OGSIVEO 醫師的熱情，我們已經是系統性的照護標準。我們期望，隨著醫生表示希望在未來更多地使用它，這種情況會有所改善。今年底，也就是進入 2025 年，我們將經歷泡罩包裝的轉型期。因此，您將能夠受益於更好的補充率，對於現在需要服用更少藥片的患者來說，更好的依從性，當然，正如我所說的，對於我們來說，100 毫克和 150 毫克的劑量是平等的。

And then certainly, that benefit of longer-term duration dosing. And now we've got clinical data, not just patient data who clearly benefit from a pain reduction standpoint, but clinical data supporting why those patients are benefiting from continued dosing here with OGSIVEO.

當然，長期服藥也有好處。現在我們獲得了臨床數據，不僅是從減輕疼痛的角度明顯受益的患者數據，還有支持為什麼這些患者會從繼續使用 OGSIVEO 中受益的臨床數據。

So I think we are in a very good position for 2025 and beyond and the ability to stack patients to have a medicine that these patients do need, better awareness of what is out there. And now with the transition of the blister pack largely behind us, we think we are very well positioned going forward. Thank you.

因此，我認為我們在 2025 年及以後處於非常有利的地位，能夠為患者提供他們真正需要的藥物，並更好地了解現有的藥物。現在，泡罩包裝的轉型已基本結束，我們認為，我們為未來的發展做好了充分準備。謝謝。

And this concludes today's call. Thank you for joining. You may now disconnect.

今天的電話會議到此結束。感謝您的加入。您現在可以斷開連線。