SpringWorks Therapeutics Inc (SWTX) 2024 Q2 法說會逐字稿

Good morning. My name is Gigi, and I'll be your conference operator today. I would like to welcome everyone to the SpringWorks Therapeutics second-quarter 2024 earnings conference call. (Operator Instructions) Thank you.

早安.我叫 Gigi，今天我將擔任你們的會議操作員。歡迎大家參加 SpringWorks Therapeutics 2024 年第二季財報電話會議。（操作員說明）謝謝。

I would now like to hand the conference over to Samantha Sandler, Senior Director of Investor Relations at SpringWorks Therapeutics.

我現在想將會議交給 SpringWorks Therapeutics 投資者關係高級總監 Samantha Sandler。

Samantha, you may now begin the conference.

莎曼珊，你現在可以開始會議了。

Thank you and good morning, everyone. Welcome to SpringWorks Therapeutics second-quarter 2024 earnings conference call. This morning, we issued a press release, which outlines our financial and operational results for the second 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 年第二季財報電話會議。今天早上，我們發布了一份新聞稿，概述了我們第二季的財務和營運表現。您可以造訪我們網站 www.springworkstx.com 的投資者和媒體部分，造訪我們今天將展示的新聞稿以及投影片。

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

今天加入我的是執行長 Saqib Islam； Bhavesh Ashar，首席商務長； Jim Cassidy 博士，首席醫療官；法蘭西斯‧佩里爾，財務長；和首席營運長 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. This 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 such statements.

在開始之前，我想提醒您，今天電話會議中所做的一些陳述屬於前瞻性陳述，存在許多風險和不確定性。這可能會導致我們的實際結果有重大差異，包括我們向 SEC 提交的報告中所述的結果。請您注意不要過度依賴這些前瞻性陳述，SpringWorks 不承擔任何更新此類陳述的義務。

I will now turn the call over to Saqib.

我現在將把電話轉給 Saqib。

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

謝謝你，山姆，也謝謝大家今天早上的加入。我很高興分享我們第二季度的業績，以及我們如何實現對毀滅性疾病患者的生活產生深遠影響的目標。

Starting with OGSIVEO for patients with desmoid tumors, we are encouraged by the strong momentum of our US launch. In the second quarter of 2024, we reported $40.2 million in net product revenue. This robust and continued growth is driven by the transformative clinical benefits from OGSIVEO, high demand from patients and physicians across treatment settings, and strong commercial execution.

從針對硬纖維瘤患者的 OGSIVEO 開始，我們對美國上市的強勁勢頭感到鼓舞。2024 年第二季度，我們的產品淨收入為 4,020 萬美元。這種強勁而持續的成長是由 OGSIVEO 的變革性臨床效益、患者和醫生在治療環境中的高需求以及強大的商業執行力所推動的。

Since our FDA approval last November, OGSIVEO has rapidly become the standard of care systemic therapy for patients with desmoid tumors. As Bhavesh will discuss in more detail, we are seeing steady growth in new patient starts as well as strong persistence from those, who previously initiated OGSIVEO therapy. Importantly, patients are reporting rapid and meaningful symptomatic relieves, which is contributing to their overall improved quality of life and their enthusiasm for OGSIVEO for their treatment.

自去年 11 月 FDA 批准以來，OGSIVEO 已迅速成為硬纖維瘤患者的護理全身治療標準。正如 Bhavesh 將更詳細討論的那樣，我們看到新患者數量的穩定增長以及先前開始 OGSIVEO 治療的患者的強烈堅持。重要的是，患者報告症狀得到快速且有意義的緩解，這有助於他們整體生活品質的提高以及他們對 OGSIVEO 治療的熱情。

We are pleased with our early launch experience and believe that we have only reached a small proportion of people with desmoid tumors, who can benefit from OGSIVEO. Our confidence in the overall patient population has continued to increase as we have gained further insights from the launch and from emerging desmoid tumor-specific claims data. Our conviction remains high in the opportunity we have in front of us to serve an increasing number of desmoid tumor patients.

我們對早期的推出體驗感到滿意，並相信我們只涵蓋了一小部分患有硬纖維瘤的患者，他們可以從 OGSIVEO 中受益。隨著我們從上市和新出現的硬纖維瘤特異性索賠數據中獲得更多見解，我們對整體患者群體的信心持續增強。我們仍然堅信我們有機會為越來越多的硬纖維瘤患者提供服務。

Turning to our investigational MEK inhibitor, mirdametinib. In the second quarter, we completed our NDA submission to the FDA for the treatment of children and adults with neurofibromatosis type 1 associated plexiform neurofibromas, or NF1-PN. Our NDA submission is based on positive data from our pivotal Phase 2b ReNeu trial which support the potential for mirdametinib to be a best-in-class therapy for both children and adults living with these devastating lifelong tumors.

轉向我們的研究性 MEK 抑制劑 Mirdametinib。第二季度，我們完成了向 FDA 提交的 NDA 申請，用於治療患有 1 型神經纖維瘤病相關叢狀神經纖維瘤（NF1-PN）的兒童和成人。我們提交的 NDA 是基於我們關鍵的 2b 期 ReNeu 試驗的積極數據，該試驗支持 Mirdametinib 有可能成為患有這些毀滅性終身腫瘤的兒童和成人的同類最佳療法。

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 were adults and 10,000 are pediatric patients. Challenges with administration and tolerability limit the use of currently available options for children, and there are no FDA-approved therapies for adults. We look forward to working with the FDA throughout our NDA review process and to advancing our commercial preparations in anticipation of our second medicine introduced to patients in 2025.

僅在美國就有約 40,000 名 NF1-PN 患者，其中 30,000 名成人和 10,000 名兒科患者，其需求尚未得到滿足。給藥和耐受性方面的挑戰限制了目前可用的兒童治療方案的使用，並且沒有 FDA 批准的成人治療方法。我們期待在整個 NDA 審查過程中與 FDA 合作，並推進我們的商業準備工作，以期在 2025 年向患者推出第二種藥物。

We are also excited about the opportunities in our emerging portfolio. We have several important efforts in development to serve additional patient populations with high unmet needs, including patients with ovarian granulosa cell tumors, multiple myeloma, and MAPK mutant solid tumors.

我們也對新興投資組合中的機會感到興奮。我們正在進行幾項重要的開發工作，為更多需求未被滿足的患者群體提供服務，包括卵巢顆粒細胞瘤、多發性骨髓瘤和 MAPK 突變實體瘤患者。

In addition, we recently began enrollment in our Phase 1 study of our investigational TEAD inhibitor SW-682, in Hippo mutant solid tumors, which represent up to 10% of cancers. Finally, we have durable IP protections for our lead molecules and a robust balance sheet that we expect to fund us through profitability.

此外，我們最近開始招募我們的研究性 TEAD 抑制劑 SW-682，用於治療 Hippo 突變實體腫瘤（佔癌症的 10%）。最後，我們為我們的先導分子提供持久的智慧財產權保護，並擁有穩健的資產負債表，我們希望透過獲利能力為我們提供資金。

I'll now hand the call to Bhavesh to discuss our progress with OGSIVEO for patients with desmoid tumors. Bhavesh?

現在，我將致電 Bhavesh，討論我們與 OGSIVEO 治療硬纖維瘤患者的進展。巴維什？

Thank you, Saqib. I'm happy to share an update on the US launch of OGSIVEO. Two full quarters into our launch, OGSIVEO is already the most prescribed systemic therapies for adults with desmoid tumors. As Saqib highlighted, in the second quarter of 2024, we generated $40.2 million in net product revenue, driven by strong demand for OGSIVEO by patients and physicians across treatment sites, real-world experience of OGSIVEO meaningful benefits, and focused commercial execution in delivering the first and only FDA-approved medicine to the desmoid tumor community.

謝謝你，薩奇布。我很高興與大家分享 OGSIVEO 在美國推出的最新消息。在我們推出整整兩個季度後，OGSIVEO 已經成為成人硬纖維瘤患者處方最多的全身療法。正如Saqib 所強調的那樣，在2024 年第二季度，我們產生了4020 萬美元的產品淨收入，這得益於各個治療地點的患者和醫生對OGSIVEO 的強勁需求、OGSIVEO 有意義的益處的實際經驗以及在交付第一個也是唯一一個獲得 FDA 批准用於硬纖維瘤領域的藥物。

We're seeing robust adoption with broad use aligned with our FDA-approved label including in newly diagnosed patients and in those seeking their next line of therapy after unsatisfactory outcomes with previous interventions.

我們看到該藥物得到了強勁的採用和廣泛的使用，符合 FDA 批准的標籤，包括新診斷的患者以及在先前幹預結果不滿意後尋求下一行治療的患者。

Physicians at centers of excellence with strong early adopters of OGSIVEO, the majority of them have now treated multiple patients and continue to add new patients. We're also pleased with the continued uptake amongst physicians and other academic and community centers, where we are also seeing steady new patient starts.

卓越中心的醫生是 OGSIVEO 的早期採用者，其中大多數現在已經治療了多名患者，並繼續增加新患者。我們也對醫生和其他學術和社區中心的持續採用感到高興，我們也看到穩定的新患者開始使用。

In addition, we've received consistent feedback from both patients and physicians on OGSIVEO's life altering impact. Patients are experiencing rapid and significant symptom relief, notably pain reduction, helping them to get back to their daily lives. Enhancing the patient experience with OGSIVEO has been an area of focus this quarter.

此外，我們也收到了患者和醫生對 OGSIVEO 改變生活的影響的一致回饋。患者的症狀迅速顯著緩解，特別是疼痛減輕，幫助他們恢復日常生活。透過 OGSIVEO 增強患者體驗一直是本季的重點領域。

We're pleased with the successful introduction of the 150-milligram and 100-milligram strength OGSIVEO tablets in convenient blister packaging. The new product format has seen strong adoption to date, validating the importance of this innovation for patients.

我們很高興成功推出採用方便泡罩包裝的 150 毫克和 100 毫克濃度 OGSIVEO 片劑。迄今為止，新產品形式已被廣泛採用，證實了這項創新對患者的重要性。

Patients prescribed OGSIVEO continue to have broad access with reimbursement across payers. Commercial and government insurers are broadly reimbursing OGSIVEO and formal coverage policies are in place for over 90% of commercially covered lives. Across the payer landscape, there is clear recognition of the clinical value of our medicine as an NCCN Category 1 preferred treatment.

開立 OGSIVEO 處方的患者可以繼續獲得廣泛的付款人報銷。商業和政府保險公司廣泛補償 OGSIVEO，並且超過 90% 的商業承保人壽都有正式的承保政策。在整個付款人格局中，我們的藥物作為 NCCN 1 類首選治療的臨床價值得到了明確的認可。

And in June, the Desmoid Tumor Working Group guidelines were published in JAMA Oncology, highlighting OGSIVEO's incorporation into the treatment algorithm as the first and only approved drug for desmoid tumors.

6 月，硬纖維瘤工作小組指南在《美國醫學會雜誌腫瘤學》上發表，強調 OGSIVEO 已納入治療流程，成為第一個也是唯一一個核准的硬纖維瘤藥物。

In just seven months on market, OGSIVEO has become the systemic standard of care for desmoid tumors based on our analysis of prescription data and we're excited to leverage this position of strength to reach many more patients with this disease. We've also continued to receive highly positive feedback from prescribers and patients on their experiences with OGSIVEO.

根據我們對處方數據的分析，OGSIVEO 上市僅七個月，就已成為硬纖維瘤的系統護理標準，我們很高興能夠利用這一優勢來幫助更多患有這種疾病的患者。我們也持續收到處方者和患者對 OGSIVEO 體驗的高度正面回饋。

In a recent survey of 110 oncologists, 95% of OGSIVEO prescribers expressed satisfaction with their experience. More than 85% of prescribers prefer it over off-label systemics, which are known to have inconsistent efficacy and tolerability challenges, further supporting OGSIVEO's position as a systemic therapy of choice. In addition, most physicians said that they are likely to use OGSIVEO as a frontline treatment, indicating treatment with OGSIVEO at the earliest opportunity for their adult patients.

最近對 110 名腫瘤科醫生進行的一項調查顯示，95% 的 OGSIVEO 處方醫生對他們的體驗表示滿意。超過 85% 的處方者更喜歡它，而不是標籤外系統用藥，眾所周知，後者俱有不一致的療效和耐受性挑戰，這進一步支持了 OGSIVEO 作為首選全身治療的地位。此外，大多數醫生表示他們很可能使用 OGSIVEO 作為第一線治療，這表明他們的成年患者儘早接受 OGSIVEO 治療。

Further, we're hearing consistent feedback from patients of profound symptom relief on OGSIVEO, including patients experiencing rapid and meaningful improvements in pain within days of initiating treatment. The strength of the real-world feedback, which is consistent with our clinical trial experience, we'll continue to solidify OGSIVEO as the standard of care systemic treatment for patients with desmoid tumors.

此外，我們聽到患者對 OGSIVEO 症狀明顯緩解的一致回饋，包括在開始治療後幾天內疼痛得到快速且有意義的改善的患者。現實世界回饋的強度與我們的臨床試驗經驗一致，我們將繼續鞏固 OGSIVEO 作為硬纖維瘤患者的護理系統治療標準。

Turning now to the opportunity we see ahead of us. There are up to 1,650 newly diagnosed patients annually. Our market research supports that the vast majority of physicians are likely to use OGSIVEO as a frontline treatment and we're already seeing uptake of OGSIVEO as the first intervention. Our research has previously pointed to up to 7,000 actively managed patients in the US each year.

現在轉向我們看到的機會。每年新診斷患者多達1,650名。我們的市場研究表明，絕大多數醫生可能會使用 OGSIVEO 作為一線治療，並且我們已經看到 OGSIVEO 作為第一種幹預措施。我們先前的研究表明，美國每年有多達 7,000 名接受積極管理的患者。

Our early launch results, as well as desmoid tumor specific ICD-10 claims data, have continued to validate the size of this currently addressable patient pool, and we now view this estimate as conservative.

我們的早期發布結果以及硬纖維瘤特異性 ICD-10 索賠數據繼續驗證了當前可尋址患者庫的規模，我們現在認為這一估計是保守的。

The role of systemic therapy is continuing to increase among patients who require active treatment with surgery being deprioritized in treatment guidelines. With OGSIVEO as the first choice systemic, we're confident that there continues to be a substantial opportunity for growth in this patient population. In addition, there's a sizable diagnosed prevalent population of 30,000 people overall.

在需要積極治療的患者中，全身性治療的作用不斷增強，而手術在治療指引中已不再優先考慮。由於 OGSIVEO 作為首選系統，我們相信該患者群體仍然存在巨大的成長機會。此外，確診流行人群總數達 3 萬人。

We know that the majority of desmoid tumor patients receive active intervention over the course of their disease and hence, a meaningful proportion of these patients who, are currently on the sidelines, could potentially be addressed with a new treatment option. We have seen robust adoption to date and continue to have strong conviction in the sizable opportunity ahead of us to continue serving adults with desmoid tumors at all stages of treatment.

我們知道，大多數硬纖維瘤患者在病程中都會接受積極的干預，因此，目前處於觀望狀態的這些患者中有很大一部分可能會透過新的治療方案得到解決。到目前為止，我們已經看到了廣泛的採用，並且仍然堅信我們面前有巨大的機會，可以繼續為患有硬纖維瘤的成人患者提供各個治療階段的服務。

Our success thus far positions us well for continued momentum in the second half of the year and beyond. We're gratified to have earned the advocacy of Desmoid tumor experts through their collaboration in the DeFi study as well as engagement following the approval of OGSIVEO.

迄今為止，我們的成功為我們在下半年及以後的持續發展奠定了良好的基礎。我們很高興透過 DeFi 研究中的合作以及 OGSIVEO 批准後的參與贏得了 Desmoid 腫瘤專家的支持。

Our commercial efforts aim to amplify their voices to educate and improve outcomes for patients. This comes in the form of providing opportunities for these leaders to educate the broader desmoid tumor community including physicians, nurses, advocates, patients, and caregivers on guideline recommended treatment approaches.

我們的商業努力旨在擴大他們的聲音，以教育和改善患者的治療結果。其形式是為這些領導者提供機會，向更廣泛的硬纖維瘤社區（包括醫生、護士、倡導者、患者和護理人員）提供指南推薦的治療方法的教育。

Importantly, this includes educating on the role of systemic, the limitations of surgical intervention and the availability of OGSIVEO as an FDA-approved and NCCN Category 1 preferred treatment option. Education and peer-to-peer information and experience sharing are critical avenues to increasing awareness of OGSIVEO and will continue to support increased breadth and depth of prescribing. Continuing to address the needs of patients also remains paramount, and we're highly focused on supporting positive experiences with OGSIVEO.

重要的是，這包括宣傳全身治療的作用、手術幹預的局限性以及 OGSIVEO 作為 FDA 批准的和 NCCN 1 類首選治療選擇的可用性。教育以及同儕資訊和經驗分享是提高 OGSIVEO 認識的重要途徑，並將繼續支持擴大處方的廣度和深度。持續滿足患者的需求仍然至關重要，我們高度重視支持 OGSIVEO 的正面體驗。

In mid-May, we successfully introduced our 150-milligram and 100-milligram strength tablets in convenient blister packaging. This new product format was developed as an innovation for patients to increase convenience and adherence by reducing the daily pill intake and simplifying morning and evening dosing. We have seen a strong transition to this new format through the second quarter and expect this transition to continue over the next three months.

5 月中旬，我們成功推出了採用方便泡罩包裝的 150 毫克和 100 毫克規格片劑。這種新產品形式的開發是對患者的創新，透過減少每日藥丸攝取量和簡化早晚給藥來提高便利性和依從性。我們在第二季度看到了向這種新格式的強勁過渡，並預計這種過渡將在未來三個月內持續下去。

Additionally, we're expanding our educational resources and delivering best-in-class patient services through SpringWorks Care connections to further support the treatment journey with OGSIVEO. We also continue to generate data to support the strong clinical profile of OGSIVEO and are advancing our efforts to expand OGSIVEO into additional geographies.

此外，我們正在擴大我們的教育資源，並透過 SpringWorks Care 連結提供一流的患者服務，以進一步支持 OGSIVEO 的治療之旅。我們也繼續產生數據來支援 OGSIVEO 強大的臨床概況，並正在努力將 OGSIVEO 擴展到其他地區。

In the second quarter, we presented additional data from our Phase 3 DeFi trial at ASCO that reinforced the robust efficacy and manageable safety profile of OGSIVEO including in hard-to-treat subgroups, such as patients with characteristics associated with poor prognosis and those with APC mutations, which can be a more aggressive form of the disease.

第二季度，我們提供了來自ASCO 的3 期DeFi 試驗的更多數據，這些數據增強了OGSIVEO 的穩健療效和可管理的安全性，包括在難以治療的亞組中，例如具有不良預後相關特徵的患者和患有APC 的患者突變，這可能是一種更具侵襲性的疾病形式。

In an oral presentation at ASCO, the file was also showcased as an exemplar of one of the most comprehensive assessments of ovarian function in an oncology clinical trial to date and a best practice for evaluating a drug's effect on ovarian function for future cancer trials in accordance with ASCO guidelines.

在 ASCO 的口頭報告中，該文件也被展示為迄今為止腫瘤學臨床試驗中最全面的卵巢功能評估之一的範例，也是評估藥物對卵巢功能影響的最佳實踐，以供未來癌症試驗使用。符合ASCO 指南。

This analysis included updated data on investigator-reported resolution of ovarian toxicity and DeFi which further supported the transient nature of ovarian toxicity in both the majority of patients who stay on OGSIVEO therapy and all those who stopped treatment for any reason.

這項分析包括研究者報告的卵巢毒性和 DeFi 解決方案的最新數據，進一步支持了大多數繼續接受 OGSIVEO 治療的患者和所有因任何原因停止治療的患者的卵巢毒性的短暫性。

Turning to upcoming milestones. We're working closely with the European regulators as they review our marketing authorization application and we are excited by the potential to receive approval from the European Commission in 2025.

轉向即將到來的里程碑。我們正在與歐洲監管機構密切合作，審查我們的行銷授權申請，我們對 2025 年獲得歐盟委員會批准的可能性感到興奮。

We also look forward to sharing long-term follow-up data from DeFi at a medical conference before the end of the year. In our Phase 1 and Phase 2 studies, patients remain on OGSIVEO for a median of over four years. And at the time of the Phase 3 DeFi trial data cutoff, median treatment duration was approaching two years.

我們也期待在年底前的醫學會議上分享 DeFi 的長期追蹤數據。在我們的第 1 期和第 2 期研究中，患者繼續服用 OGSIVEO 的時間中位數超過四年。在第三階段 DeFi 試驗數據截止時，中位治療持續時間接近兩年。

With these long-term follow-up data from DeFi, we plan to provide an update on the continued anti-tumor activity and overall clinical benefit provided by OGSIVEO with longer durations of treatment. The ability for patients to stay on therapy is critical, given the persistent morbidities associated with this disease and we believe these longer-term results from DeFi will further support the potential for extended treatment durations.

借助來自 DeFi 的這些長期追蹤數據，我們計劃提供 OGSIVEO 在較長治療時間內提供的持續抗腫瘤活性和整體臨床益處的最新資訊。考慮到與這種疾病相關的持續發病率，患者堅持治療的能力至關重要，我們相信 DeFi 的這些長期結果將進一步支持延長治療持續時間的潛力。

I'll now turn it over to Dr. Jim Cassidy, our Chief Medical Officer, to discuss the progress we're making with our MEK inhibitor, mirdametinib with children and adults with NF1-PN. Jim?

現在我將把它交給我們的首席醫療官 Jim Cassidy 博士，討論我們的 MEK 抑制劑 Mirdametinib 在治療患有 NF1-PN 的兒童和成人方面所取得的進展。吉姆？

Thanks, Bhavesh. I'm glad to provide an update on our progress developing mirdametinib as a potentially best-in-class therapy for patients with NF1-PN, which is a highly morbid and lifelong disease that affects both children and adults.

謝謝，巴維什。我很高興向大家介紹我們開發 Mirdametinib 的最新進展，該藥物可能是 NF1-PN 患者的同類最佳療法，NF1-PN 是一種高發病率和終生疾病，影響兒童和成人。

To start, there is a significant opportunity to improve outcomes for these patients that 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 sheaths and can cause severe disfigurement, pain, and functional impairment.

首先，這是一個改善這些患者預後的重大機會，這些患者在美國約有 10 萬名 NF1 患者。這些人終生有 30% 至 50% 的風險患有叢狀神經纖維瘤，沿著周圍神經鞘生長，可導致嚴重的毀容、疼痛和功能障礙。

We estimate that there are approximately 40,000 patients with NF1-PN in the US today. The majority of them are adults who currently do not have an approved therapy. As there is no specific demographic win 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。其中大多數是目前尚未獲得批准治療的成年人。由於這種疾病沒有特定的人口統計勝利，我們估計在美國以外也有一定比例的 NF1-PN 患者。

While systemic therapies or treatment of choice and MEK inhibitors have been clinically validated as a class in this indication, there are no formal treatment guidelines and our market research shows that only a small portion of NF1-PN patients have been treated with a targeted therapy.

雖然全身療法或首選療法和MEK 抑制劑已被臨床驗證為該適應症的一類，但尚無正式的治療指南，而且我們的市場研究表明，只有一小部分NF1-PN 患者接受了標靶療法。

We have done considerable work to understand the disease state, current treatment paradigm, and physician and patient preferences, and taken as a whole, our research supports that patients are in need of new options. This is illustrated by a highly fragmented treatment landscape with significant use of off-label therapies even in pediatric patients for whom there is an approved medicine.

我們做了大量工作來了解疾病狀況、目前的治療模式以及醫生和患者的偏好，總的來說，我們的研究支持患者需要新的選擇。高度分散的治療模式就說明了這一點，即使在有核准藥物的兒科患者中，也大量使用標籤外療法。

People living with NF1-PN have substantial needs that are not met by current options and bringing to market a new systemic therapy could allow many more patients to be treated. As we'll discuss, the positive results from our pivotal Phase 2b ReNeu support mirdametinib's to be a first-in-class therapy for adults with in NF1-PN and the best-in-class option for pediatric patients. The new results were presented at three medical conferences in the second quarter, including during an oral session at ASCO.

NF1-PN 患者有大量需求，但目前的選擇無法滿足，將新的全身療法推向市場可以讓更多患者得到治療。正如我們將討論的，我們的關鍵 2b 期 ReNeu 的積極結果支持 mirdametinib 成為成人 NF1-PN 患者的一流療法，也是兒科患者的一流選擇。新結果在第二季的三場醫學會議上公佈，其中包括 ASCO 的口頭會議。

These presentations are improving awareness and building enthusiasm for our positive results amongst the physician community. The FCC data across both adult and pediatric cohorts in ReNeu showed significant reductions in the size of NF1-PN tumors with robust objective response rate confirmed by blinded independent central review.

這些演講提高了醫生界對我們積極成果的認識並激發了熱情。ReNeu 成人和兒童群的 FCC 數據顯示，NF1-PN 腫瘤的大小顯著減小，且盲法獨立中央審查證實了穩健的客觀緩解率。

In addition, we saw very deep responses that have not been seen before in published studies of this disease. The majority of patients with a confirmed object of response experienced a tumor reduction of greater than 50% and reductions of up to 90% were seen in both cohorts.

此外，我們也看到了非常深刻的反應，這是以前發表的針對這種疾病的研究中從未見過的。大多數已確認緩解的患者的腫瘤縮小了 50% 以上，兩個隊列中的腫瘤縮小幅度高達 90%。

This is particularly significant when you consider the hard-to-treat patients that were enrolled in our study. Importantly, physician feedback suggests that these are unprecedented data and have the potential to be a meaningful differentiator.

當您考慮到我們研究中納入的難以治療的患者時，這一點尤其重要。重要的是，醫生的回饋表明這些是前所未有的數據，並且有可能成為有意義的差異化因素。

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

在兒童和成人中，mirdametinib 表現出可控制的安全性，3 級不良事件發生率較低，並且由於 AE 導致的停藥率較低。我們相信 Mirdametinib 的耐受性支持了延長治療持續時間的潛力，這對於 NF1-PN 等當前疾病非常重要，因為停止治療後治癒率很高。

In ReNeu across both cohorts, the median time on treatment was approaching two years with some patients on mirdametinib therapy for nearly four years at the time of the primary analysis. Nearly all patients that completed the treatment phase continued on therapy in the long-term follow-up portion of the study. The potential for mirdametinib to enhance patient quality of life is also very meaningful.

在 ReNeu 的兩個隊列中，中位治療時間接近兩年，其中一些患者在初步分析時接受了 Mirdametinib 治療近四年。幾乎所有完成治療階段的患者都在研究的長期追蹤部分繼續接受治療。Mirdametinib 提升病患生活品質的潛力也非常有意義。

Pain is a common symptom in NF1-PN and current clinical practice recommendations indicate that this is a critical factor in treatment initiation decisions. Further, in many cases, the primary goal of treatment is improvement of such PN associated mobilities.

疼痛是 NF1-PN 的常見症狀，目前的臨床實踐建議表明這是開始治療決策的關鍵因素。此外，在許多情況下，治療的主要目標是改善與 PN 相關的活動能力。

Pain was the most commonly reported baseline mobility in the ReNeu trial, so significant both adults and children, including those with the most ability taking pain, reported early sustained and claimed significant reductions in pain severity and pain interference over the course of mirdametinib's treatment.

疼痛是ReNeu 試驗中最常報告的基線活動度，因此，成人和兒童，包括那些最有能力承受疼痛的人，都報告了早期持續的疼痛嚴重程度和疼痛幹擾，並聲稱在Mirdametinib 治療過程中疼痛嚴重程度和疼痛幹擾顯著降低。

Lastly, we believe that mirdametinib's convenient dosing regimen, which provides adult-treatment of holiday and a pediatric-friendly dispersible formulation to further optimize the patient experience and potentially enhance compliance. In ReNeu children and caregiver reports were highly positive in this regard, with maximum acceptability scores for ease of slowing and willingness to continue to take the dispersible tablet.

最後，我們相信 Mirdametinib 方便的給藥方案，提供成人假期治療和兒科友善的分散製劑，可進一步優化患者體驗並可能提高依從性。在 ReNeu 中，兒童和照顧者在這方面的報告非常積極，對於放慢速度的輕鬆程度和繼續服用分散片的意願給出了最高可接受分數。

The totality of the ReNeu data reinforces our belief that mirdametinib can address strong desire amongst both physicians and patients for our new therapy that offers robust tumor and symptomatic control, a manageable safety profile, and convenient dosing regimen, all of which, we expect will enable patients to remain on therapy for an extended period of time.

ReNeu 數據的整體強化了我們的信念，mirdametinib 可以滿足醫生和患者對我們新療法的強烈渴望，該療法提供強大的腫瘤和症狀控制、可管理的安全性和方便的給藥方案，我們預計所有這些都將能夠實現患者需要長期接受治療。

Looking ahead, we are making meaningful progress advancing mirdametinib towards potential regulatory approval in 2025. Mirdametinib was granted orphan drug designation by both the FDA and the European Commission.

展望未來，我們正在取得有意義的進展，推動 Mirdametinib 預計將在 2025 年獲得監管機構批准。Mirdametinib 被 FDA 和歐盟委員會授予孤兒藥稱號。

And the FDA also granted fast track and rare pediatric disease designations for NF1-PN. We completed our NDA submission to the FDA at the end of June, and we anticipate announcing our PDUFA date in the coming weeks.

FDA 也授予 NF1-PN 快速通道和罕見兒科疾病資格。我們於 6 月底完成了向 FDA 提交的 NDA 申請，預計將在未來幾週內宣布 PDUFA 日期。

We're also on track to complete the submission of our European marketing authorization within this half. In addition, that our new results will continue to be showcased at upcoming medical congresses and we expect the results to be published in our peer review journal later this year.

我們也預計在今年上半年完成歐洲行銷授權的提交。此外，我們的新結果將繼續在即將舉行的醫學大會上展示，我們預計結果將在今年稍後發表在我們的同行評審期刊上。

And now Frank Perier, our Chief Financial Officer, will discuss our second-quarter financial results. Frank?

現在，我們的財務長 Frank Perier 將討論我們第二季的財務表現。坦率？

Thank you, Jim. I'll now summarize a few highlights from our second quarter 2024 financial results. Starting with revenues. We recorded $40.2 million of OGSIVEO net product revenue in the second quarter. This brings our 2024 year-to-date OGSIVEO net product revenue to $61.2 million.

謝謝你，吉姆。現在，我將總結 2024 年第二季財務業績的一些亮點。從收入開始。第二季 OGSIVEO 產品淨收入為 4,020 萬美元。這使得我們 2024 年迄今的 OGSIVEO 產品淨收入達到 6,120 萬美元。

Our total operating expenses increased compared to the second quarter and the first half of 2023, driven by the commercial activities to support the US launch of OGSIVEO and the anticipated US launch of mirdametinib in both adults and children with NF1-PN.

與2023 年第二季和上半年相比，我們的總營運費用有所增加，這是由於支持在美國推出OGSIVEO 的商業活動以及預計在美國推出治療NF1-PN 成人和兒童的Mirdametinib 的商業活動推動的。

We have a strong balance sheet supporting our clear path to profitability with $522 million in cash, cash equivalents, and marketable securities as of the end of the second quarter. Lastly, we have a durable operating plan designed to fund multiple global product launches and to enable the continued investment in expansion opportunities across our pipeline.

截至第二季末，我們擁有強大的資產負債表，擁有 5.22 億美元的現金、現金等價物和有價證券，支持我們明確的獲利之路。最後，我們制定了持久的營運計劃，旨在為多個全球產品的發布提供資金，並持續投資於我們產品線的擴張機會。

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

這樣，我會將電話轉回 Saqib。

Thank you, Frank. As we've discussed this morning, we are very pleased with the continued strong momentum of our US launch of OGSIVEO for adults with desmoid tumors and are working with urgency to bring mirdametinib to children and adults with NF1-PN.

謝謝你，弗蘭克。正如我們今天早上所討論的，我們對在美國推出針對成人硬纖維瘤的 OGSIVEO 的持續強勁勢頭感到非常高興，並正在緊急努力將 Mirdametinib 帶給患有 NF1-PN 的兒童和成人。

In parallel with these commercial efforts, we are enthusiastic about our emerging portfolio. Nirogacestat is being studied in a Phase 2 trial in ovarian granulosa cell tumors, which is fully enrolled. These tumors account for approximately 5% of all ovarian cancers and like desmoid tumors, this is a meaningful patient population for which there are no FDA-approved therapies.

在這些商業努力的同時，我們對我們的新興產品組合充滿熱情。Nirogacestat 正在進行卵巢顆粒細胞瘤的 2 期試驗，該試驗已全部入組。這些腫瘤約佔所有卵巢癌的 5%，與硬纖維瘤一樣，這是一個有意義的患者群體，目前尚無 FDA 批准的治療方法。

In multiple myeloma, we've established clinical proof-of-concept for nirogacestat in combination settings with several BCMA-directed agents and are continuing to collaborate with a number of industry and academic partners to further this strategy.

在多發性骨髓瘤中，我們已經建立了 nirogacestat 與幾種 BCMA 導向藥物聯合治療的臨床概念驗證，並繼續與許多行業和學術合作夥伴合作，以推進這項策略。

We're also pursuing expansion opportunities for mirdametinib in several monotherapy and combination therapy settings, promising data from a Phase 1/2 study of mirdametinib in pediatric low-grade glioma were recently presented at the International Symposium on Pediatric Neuro-oncology meeting and several combination studies are currently ongoing, including the trial with MAP kinase lifirafenib in advanced solid tumors with MAP kinase mutations and with BeiGene's lifirafenib in NRAS-mutant solid tumors.

我們也正在尋求Mirdametinib 在多種單一療法和聯合療法中的擴展機會，最近在兒科神經腫瘤學國際研討會上公佈了mirdametinib 在兒科低級別膠質瘤中的1/2 期研究的有希望的數據，以及一些聯合療法目前正在進行的研究包括 MAP 激酶 lifirafenib 在 MAP 激酶突變的晚期實體瘤中的試驗以及百濟神州的 lifirafenib 在 NRAS 突變實體瘤中的試驗。

Brimarafenib is also being explored as a monotherapy in adults with RAF mutant solid tumors. And we're looking to confirm the efficacy signal we reported last year in the dose escalation study in several ongoing dose expansion cohorts.

Brimarafenib 也正在探索作為 RAF 突變實體瘤成人的單一療法。我們希望確認我們去年在幾個正在進行的劑量擴展隊列的劑量遞增研究中報告的療效訊號。

Additionally, SW-682, our oral TEAD inhibitor is now in the clinic. This program is designed to treat tumors with Hippo pathway mutations, which can occur in up to 10% of cancers, including mesothelioma and head and neck cancer. We believe that there is a meaningful opportunity with SW-682 for SpringWorks to develop a novel medicine for these cancers.

此外，我們的口服 TEAD 抑制劑 SW-682 現已進入臨床。該計畫旨在治療具有 Hippo 通路突變的腫瘤，這種突變可能發生在高達 10% 的癌症中，包括間皮瘤和頭頸癌。我們相信 SW-682 為 SpringWorks 提供了一個有意義的機會來開發一種治療這些癌症的新藥。

Lastly, we are also advancing several internally discovered preclinical stage programs, and we look forward to sharing more about these efforts as they progress.

最後，我們也正在推動幾個內部發現的臨床前階段項目，我們期待在這些項目取得進展時分享更多有關這些工作的資訊。

To close, we are very pleased with our accomplishments in the first half of this year and have multiple milestones and data readouts ahead that we look forward to sharing. These include long-term follow-up data from our DeFi trial, which we believe will support the benefits of extended treatment durations with OGSIVEO in desmoid tumors.

最後，我們對今年上半年的成就感到非常滿意，並且我們期待分享未來的多個里程碑和數據讀數。其中包括我們 DeFi 試驗的長期追蹤數據，我們相信這些數據將支持 OGSIVEO 延長治療時間對硬纖維瘤的益處。

It also includes initial data from our Phase 2 trial of nirogacestat in ovarian granulosa cell tumors and we expect the full ReNeu trial results to be published in a peer-reviewed journal. Our focus for the remainder of the year will be to continue building on OGSIVEO's momentum in the US, while working to bring this medicine to patients in Europe and other geographies, to advance our regulatory and commercial preparations for mirdametinib in anticipation of serving patients with NF1-PN in the US and Europe, and to progress our diversified emerging portfolio in an efficient manner.

它還包括我們的 nirogacestat 治療卵巢顆粒細胞瘤 2 期試驗的初步數據，我們預計完整的 ReNeu 試驗結果將在同行評審期刊上發表。今年剩餘時間裡，我們的重點將是繼續鞏固OGSIVEO 在美國的發展勢頭，同時努力將這種藥物帶給歐洲和其他地區的患者，推進我們對Mirdametinib 的監管和商業準備工作，以期為NF1 患者提供服務-在美國和歐洲的PN，並以有效的方式推進我們多元化的新興投資組合。

We are confident that our strong foundation will support our continued success as we deliver on our mission to change the lives of people suffering from devastating diseases.

我們相信，在我們履行改變遭受毀滅性疾病之苦的人們的生活的使命時，我們堅實的基礎將支持我們不斷取得成功。

As always, I would like to thank the patients and investigators who participated in our clinical trials, our patient advocacy partners and collaborators, and our team of SpringWorks workers.

一如既往，我要感謝參與我們臨床試驗的患者和研究人員、我們的患者倡導夥伴和合作者以及我們的 SpringWorks 工作人員團隊。

We're now happy to take questions. Operator?

我們現在很樂意回答問題。操作員？

(Operator Instructions) Anupam Rama, JPMorgan.

（操作員指令）Anupam Rama，摩根大通。

Hey, guys. Congrats on all the progress. Just a quick one for me. What are you seeing from both new prescribers and repeat prescribers for OGSIVEO and in the early innings, the wait-and-watch population that's coming in to seek treatment for OGSIVEO? Thanks so much.

嘿，夥計們。祝賀所有的進步。對我來說只是一個快速的。您對 OGSIVEO 的新處方者和重複處方者以及在早期幾局中前來尋求 OGSIVEO 治療的觀望人群有何看法？非常感謝。

Bhavesh, I'll let you take that.

巴韋什，我會讓你接受的。

Yeah. Thanks, Anupam. On the repeat versus new, obviously, we saw a good amount of new prescribers in the initial months of the launch. As you'd expect, we've started to see repos coming in at a regular pace from these initial starts, but supported by continued new patient starts from new patients not being acquired in the second quarter as well.

是的。謝謝，阿努帕姆。顯然，在重複與新處方方面，我們在推出的最初幾個月看到了大量新處方者。正如您所期望的那樣，我們已經開始看到回購從最初的開始就以正常的速度進行，但受到第二季度未獲得的新患者的持續新患者的支持。

As you would expect, the total proportion of business coming from existing patients versus new patient starts is increasing over time. And so that's a positive development. From a wait-and-watch perspective, we do know, obviously, that the proportion of the DT patient population there is -- is under active surveillance at any point in time. However, we do know that over 90% of these patients received some active intervention during the course of their disease.

正如您所期望的那樣，來自現有患者的業務總比例與新患者的業務總比例隨著時間的推移而增加。這是一個積極的發展。從觀望的角度來看，我們顯然知道 DT 患者群體的比例在任何時間點都處於積極監測之下。然而，我們確實知道，超過 90% 的患者在患病過程中接受了一些積極的干預。

Now with the availability of the first and only FDA-approved treatment, the opportunity ahead of us and supported by treatment guidelines, which favor systemic therapy, supported by the positive experiences that patients and physicians are seeing with OGSIVEO in the early innings of the launch, the opportunity ahead of us is to try and drive faster treatment for these patients under active surveillance. And so we do expect the proportion of active surveillance patients to be dropping over time.

現在，隨著第一個也是唯一一個FDA 批准的治療方法的出現，我們面臨著機會，並得到治療指南的支持，這些指南有利於全身治療，並得到患者和醫生在OGSIVEO 上市初期看到的積極體驗的支持擺在我們面前的機會是嘗試為這些處於主動監測的患者提供更快的治療。因此，我們確實預期主動監測患者的比例會隨著時間的推移而下降。

Yaron Werber, TD Cowen.

亞龍·韋伯，TD·考恩。

Great. Thanks for taking my questions. Congrats also on a nice quarter. Maybe I have a couple of interrelated questions. One, can you just give us a sense on inventories for the quarter for OGSIVEO?

偉大的。感謝您回答我的問題。也恭喜您度過了一個美好的季度。也許我有幾個相互關聯的問題。第一，您能為我們介紹一下 OGSIVEO 本季的庫存狀況嗎？

And then secondly, just a follow-on Anupam's question. It's -- one would imagine that the academic centers are probably the early adopters, and they're moving quickly as patients are coming in to use OGSIVEO. What are you seeing in the community? Maybe just give us a little bit of sense of the breadth of usage. Thank you.

其次，這是 Anupam 的後續問題。人們可以想像，學術中心可能是早期採用者，隨著患者開始使用 OGSIVEO，他們正在迅速採取行動。你在社區看到了什麼？也許只是讓我們對使用的廣度有一點了解。謝謝。

Bhavesh, I will turn to you again for that.

Bhavesh，我會再向你求助。

Yeah. Thank you. So from an inventory standpoint, the overall impact of inventory in the second quarter was minimal. The stocking levels were generally aligned with the demand that we're seeing. And similar to prior quarters, inventory was not a key driver of performance this quarter.

是的。謝謝。所以從庫存的角度來看，第二季庫存的整體影響很小。庫存水準總體上與我們看到的需求一致。與前幾季類似，庫存並不是本季業績的關鍵驅動因素。

From a community dynamic perspective, first of all, I'll say that from -- as we said in our prepared comments, there is a deeper pool of patients overall than we originally estimated. And we started to break into this aggregate to the patients that are up greater than 7,000 actively managed patients.

從社區動態的角度來看，首先，我要說的是，正如我們在準備好的評論中所說，總體上患者數量比我們最初估計的要多。我們開始將這群人細分為超過 7,000 名積極管理的患者。

We are -- as you highlighted, we are pleased with the update in the Centers of Excellence, we saw breadth of prescribing in the early months of the launch, we saw depth of prescribing in the second quarter.

正如您所強調的，我們對卓越中心的更新感到滿意，我們在推出的最初幾個月看到了處方的廣度，我們在第二季度看到了處方的深度。

Specifically addressing your question around community, we've started to see good adoption in the community centers, where we continue to drive breadth and -- but we still have an opportunity, right? With the broad pool of patients, we have an opportunity both to continue to drive breadth of prescribing, but also those who experience -- who do prescribe OGSIVEO to drive depth of prescribing.

具體來說，針對您關於社區的問題，我們已經開始在社區中心看到良好的採用，我們繼續擴大社區的廣度，但我們仍然有機會，對嗎？有了廣泛的患者群體，我們有機會繼續推動處方的廣度，也有機會那些有經驗的人——那些確實開過 OGSIVEO 處方的人來推動處方的深度。

Now, I'll highlight a couple of things in that regard. First of all, our ability to be in the right place at the right time for these community clinics has been significantly enhanced by the availability of the desmoid tumor-specific ICD-10 codes. And so we're able to direct our sales team to be in those clinics when a patient is available for treatment.

現在，我將強調這方面的一些事情。首先，由於硬纖維瘤特異性 ICD-10 代碼的可用性，我們在正確的時間出現在正確的地點為這些社區診所提供服務的能力得到了顯著增強。因此，當患者可以接受治療時，我們能夠指導我們的銷售團隊前往這些診所。

And then secondly, the educational efforts that we're driving both around the availability of OGSIVEO as the first and only treatment option for desmoid tumor patients, but also treatment guidelines, which do favor systemic therapy, gives us confidence in the ability for us to drive depth in that community segment as well.

其次，我們圍繞 OGSIVEO 作為硬纖維瘤患者的第一個也是唯一的治療選擇的可用性以及確實有利於全身治療的治療指南所推動的教育工作，使我們對我們的能力充滿信心也推動該社區部分的深度。

Corinne Jenkins, Goldman Sachs.

科琳·詹金斯，高盛。

Hey. Good morning, guys. I guess you've talked a little bit about having some more visibility on this patient population given the ICD-10 codes and potentially as you move to these blister packs going forward. I guess, as you look at that, where have you identified the pockets where you see the greatest opportunity for near and intermediate-term growth and what are you doing tactically to reach that patient population and keep them on therapy?

嘿。早安，夥計們。我想您已經談過，考慮到 ICD-10 代碼，以及隨著您今後轉向這些泡罩包裝，對這群患者有更多的了解。我想，當您看到這一點時，您在哪裡找到了近期和中期增長的最大機會，以及您在戰術上採取了哪些措施來接觸患者群體並讓他們繼續接受治療？

And then I did want to ask also on mirdametinib, maybe with the launch next year, where do you see like the low-hanging fruit with respect to initial adoption and how should we think about the trajectory of the early launch compared to what you've accomplished here with OGSIVEO?

然後我確實想問一下關於 Mirdametinib 的問題，也許是明年推出，您認為初步採用方面容易實現的目標在哪裡？事嗎？

Thanks, Corinne, for the series of questions, but we're going to try and answer all of them. I think as we think of mirdametinib, we view that opportunity is actually quite meaningful. And as I think of low-hanging fruit, I think we're very comfortable saying that this is an opportunity that is actually at least as large as what we see in desmoid tumors. And that's driven by a number of factors. One, by the size of the patient population, right?

謝謝科琳提出一系列問題，但我們將嘗試回答所有這些問題。我認為當我們想到mirdametinib時，我們認為這個機會實際上是非常有意義的。當我想到唾手可得的成果時，我認為我們可以很輕鬆地說，這是一個實際上至少與我們在硬纖維瘤中看到的機會一樣大的機會。這是由許多因素所驅動的。一，依照患者人數的大小，對吧？

We talked about 40,000 patients in the US and a proportionate number outside the US. And one-third of those are -- excuse me, one-quarter of those are pediatric and three-quarters of those are adults. So the opportunity for us to have a best-in-class treatment for pediatric and a first-in-class treatment for adults, we think gives us a meaningful target.

我們討論了美國的 40,000 名患者以及美國以外的相應數量的患者。其中三分之一是──對不起，其中四分之一是兒科，四分之三是成人。因此，我們認為，我們有機會為兒科提供一流的治療，為成人提供一流的治療，這給了我們一個有意義的目標。

Second, the physicians in this space actually themselves, even in the pediatric setting, believe that their patients are not being served as broadly as they could be. And so we think there's an opportunity there. And third, you can use Koselugo revenues, which now run rate just in the pediatric setting of about $500 million annually as a proxy for the opportunity just in that one-quarter of the market.

其次，這個領域的醫生實際上自己，即使是在兒科領域，也認為他們的病人沒有得到盡可能廣泛的服務。所以我們認為那裡有機會。第三，您可以使用 Koselugo 的收入（目前兒科領域每年約 5 億美元）作為該四分之一市場機會的代表。

And as you know, we're filing for both adults and peds. So we think the opportunity beyond, I think, the low hanging fruit implies that it's all easy. None of it is, but you've got a medicine that people are waiting for, an opportunity that is sizable and data that we believe supports a potentially best-in-class profile for mirdametinib for this disease.

如您所知，我們正在為成人和兒童進行申請。因此，我們認為，我認為，唾手可得的成果之外的機會意味著這一切都很容易。這些都不是，但你已經有了一種人們正在等待的藥物，一個巨大的機會，而且我們相信數據支持 Mirdametinib 對於這種疾病可能是同類最佳的。

Bhavesh, I'll turn to you talk about OGSIVEO.

Bhavesh，我來談談 OGSIVEO。

Yeah. No, I'd just reiterate a couple of the points. First and foremost, we're fortunate to have with OGSIVEO to be in a position of delivering a drug with transformative benefit to desmoid tumor patients, right? That is the foundation for the high awareness we have, the high satisfaction that we shared in the prepared comments as well as the strong preference that we see amongst prescribers and patients supported by broad access by the payer community.

是的。不，我只是重申幾點。首先也是最重要的是，我們很幸運能夠與 OGSIVEO 合作，為硬纖維瘤患者提供具有變革性益處的藥物，對嗎？這是我們的高度認識、我們在準備好的評論中所分享的高度滿意度以及我們在付款人社區的廣泛支持下在處方者和患者中看到的強烈偏好的基礎。

So with just seven months on the market, we become the systemic standard of care and the most prescribed systemic therapy for adult patients with desmoid tumors. And so the opportunity for us is to continue to drive depth within the centers of excellence as well as drive depth and breadth in the community segment, as I mentioned before.

因此，僅上市七個月，我們就成為成年硬纖維瘤患者的系統護理標準和最常用的系統治療方法。因此，正如我之前提到的，我們的機會是繼續推動卓越中心的深度以及社區領域的深度和廣度。

With the large pool of 7,000 -- more than 7,000 actively managed patients, we do see that we have a significant opportunity ahead of us to see continued growth for OGSIVEO.

憑藉 7,000 名（超過 7,000 名積極管理的患者）的龐大群體，我們確實看到我們面前有一個重大機會，可以看到 OGSIVEO 的持續增長。

Peter Lawson, Barclays.

彼得·勞森，巴克萊銀行。

Great. Thanks for taking the questions. Thanks for the update and congrats on the progress. First question is really just about the patient trends, how they've been looking at the month and particularly into July and then whether you're seeing any patients discontinuing? Thank you.

偉大的。感謝您提出問題。感謝您的更新並祝賀取得的進展。第一個問題實際上是關於患者趨勢，他們如何看待這個月，特別是 7 月份，然後您是否看到任何患者停止治療？謝謝。

Yeah. Thanks for the question, Peter. I think we aren't seeing any exceptional discontinuations. It's what we would have expected from the DeFi study, and I think that gives us confidence going into not just the third quarter, but the fourth quarter as well.

是的。謝謝你的提問，彼得。我認為我們沒有看到任何異常的中斷。這是我們對 DeFi 研究的預期，我認為這不僅讓我們對第三季充滿信心，而且對第四季也充滿信心。

So I think that the trend holds well. As Bhavesh highlighted, we think the patient pool is actually deeper than what we had originally estimated. And I think that portends well for the aggregate opportunity here.

所以我認為這種趨勢保持得很好。正如巴韋什所強調的那樣，我們認為患者庫實際上比我們最初估計的要深。我認為這預示著這裡的整體機會。

Fundamentally, where we are perhaps most excited is the feedback that we're getting, though. You've got patients seeing deep immediate and persistent benefits to their pain, that is causing them to want to get on therapy and want to stay on therapy. So we believe that the opportunity here continues to be sizeable.

從根本上說，我們最興奮的可能是我們收到的回饋。讓患者看到對他們的疼痛有深刻的、直接的和持久的好處，這促使他們想要接受治療並想要繼續接受治療。因此，我們相信這裡的機會仍然很大。

Michael Schmidt, Guggenheim.

邁克爾·施密特，古根漢。

Hey, guys. Good morning and congrats on a strong second-quarter result. Just a follow-up on OGSIVEO. As we think about the third quarter here coming up, some other products sometimes experience seasonality over the summer months. Is that something you may expect as well with this OGSIVEO?

嘿，夥計們。早安，恭喜第二季的強勁業績。只是 OGSIVEO 的後續行動。當我們考慮即將到來的第三季時，其他一些產品有時會在夏季經歷季節性變化。這也是您對 OGSIVEO 的期望嗎？

And then a follow-up on mirdametinib as we think about the launch next year. Obviously, you have already a product on the market. Do you expect initial switching from Koselugo over to mirdametinib -- or would you expect a predominantly penetration into the currently untreated patients with NF1-PN as we think about that next year? Thanks so much.

然後是 Mirdametinib 的後續行動，我們正在考慮明年的推出。顯然，您已經在市場上有了產品。您是否預計最初會從 Koselugo 轉向 mirdametinib？ 或者您預計明年我們會考慮主要滲透到目前未經治療的 NF1-PN 患者嗎？非常感謝。

Thank you, Michael. So I'll take the OGSIVEO question. I'll ask Dr. Edris to take the mirdametinib question. I don't think that we're immune from seasonality, I think, as we see in many other products.

謝謝你，麥可。那麼我將回答 OGSIVEO 問題。我會請 Edris 博士回答有關 Mirdametinib 的問題。我認為，正如我們在許多其他產品中看到的那樣，我認為我們不能免受季節性影響。

I would expect to see some seasonality in the summer months. But obviously, as we've said from the outset, we think the pool is deep, and we think the opportunity is significant. Badreddin?

我預計夏季會出現一些季節性變化。但顯然，正如我們從一開始就說過的，我們認為池子很深，而且我們認為機會很大。巴德雷丁？

Yeah. So with respect to our opportunity within NF1-PN for mirdametinib, I'll remind you that our NDA filing is for both pediatric and adult patients, the latter of whom represent three-quarters of the market and do not have unapproved therapy. And so we think there's quite a bit of white space there with respect to being able to serve patients who are previously untreated.

是的。因此，關於我們在NF1-PN 中為Mirdametinib 提供的機會，我要提醒您的是，我們的NDA 申請適用於兒童和成人患者，後者佔市場的四分之三，並且沒有未經批准的治療方法。因此，我們認為在為以前未經治療的患者提供服務方面還有相當多的空白。

Within the pediatric population, I think there will certainly be some patients who have been treatment experience over the years that are seeking their next line of therapy, but our market research shows that, that market is minimally penetrated as well with respect to systemic therapy. So we think there's a significant number of pediatric patients, who are also looking for their first systemic therapy option when mirdametinib becomes available.

在兒科人群中，我認為肯定會有一些多年來有治療經驗的患者正在尋求下一種治療方法，但我們的市場研究表明，該市場在全身治療方面的滲透率也很低。因此，我們認為，當 Mirdametinib 上市時，有大量兒科患者也在尋找第一個全身性治療選項。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

Hey, guys. Thanks for taking my question and congrats from us on the strong front. Any framing you can provide around the focus of the longer-term follow-up data from DeFi later this year? And maybe one quick one, if I can sneak it in. Is your expectation that you will receive accelerated review from mirdametinib, just to clarify. Thank you.

嘿，夥計們。感謝您提出我的問題，並對我們的堅強表示祝賀。您可以圍繞今年稍後 DeFi 的長期後續數據的焦點提供任何框架嗎？如果我能偷偷溜進去的話，也許可以快一點。您是否期望收到 Mirdametinib 的加速審查，只是為了澄清。謝謝。

Thank you, Alec. I'll turn to be the Badreddin.

謝謝你，亞歷克。我將成為巴德雷丁。

Sure. So with respect to the longer-term follow-up data, Alec, I'll remind you that at the time of our primary analysis, the median time on treatment for patients that were randomized to the nirogacestat arm was just under two years. And the majority of those patients were not remaining on therapy.

當然。因此，關於長期追蹤數據，Alec，我要提醒您，在我們進行初步分析時，隨機接受 nirogacestat 組的患者的中位數治療時間不到兩年。大多數患者沒有繼續接受治療。

And so what we hope to be able to share an update on later this year. It's certainly a more mature median time on treatment figure for nirogacestat treated patients as well as the trends that we see in terms of responses, how they evolve over time and the benefits that we are seeing with a longer-dated data cut on the patient reported outcomes as well.

因此，我們希望能夠在今年稍後分享最新情況。對於接受nirogacestat 治療的患者來說，這無疑是一個更成熟的中位數治療時間，以及我們在反應方面看到的趨勢、它們如何隨時間演變以及我們透過對患者報告的較長期數據削減看到的益處結果也是如此。

So that's what we're gearing up to be able to share. And I'll remind you that in Phase 1 and Phase 2, our median time on treatment was over four years in each of those studies. So there's the opportunity to really present longer-term data.

這就是我們準備分享的內容。我要提醒您的是，在第一階段和第二階段，每項研究的中位數治療時間都超過四年。因此，我們有機會真正呈現長期數據。

Thank you.

謝謝。

With respect any expectations on review timing and then review designations for the mirdametinib filing, we have not given any guidance on that topic. We'll be in a position to receive the PDUFA date from FDA about 60 days from filing, so that will be sometime late in August.

考慮到對 Mirdametinib 申請的審查時間和審查指定的任何期望，我們尚未就該主題提供任何指導。我們將能夠在提交後約 60 天收到 FDA 的 PDUFA 日期，所以這將是 8 月下旬的某個時間。

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

謝謝。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。