Crinetics Pharmaceuticals Inc (CRNX) 2025 Q1 法說會逐字稿

Welcome to the Crinetics Pharmaceuticals First Quarter 2025 Financial Results Conference Call.

歡迎參加 Crinetics Pharmaceuticals 2025 年第一季財務業績電話會議。

(Operator Instructions) I would now like to turn the call over to Gayathri Diwakar, Head of Investor Relations. Please go ahead.

（操作員指示）現在，我想將電話轉給投資者關係主管 Gayathri Diwakar。請繼續。

Thank you, operator. Good afternoon, everyone, and thank you for joining us to discuss the first quarter 2025 results. Today on the call, we have Dr. Scott Struthers, Founder and Chief Executive Officer; Dr. Dana Pizzuti, Chief Medical and Development Officer; Isabel Kalofonos, Chief Commercial Officer; and Toby Schilke, Chief Financial Officer; Dr. Alan Krasner, Chief Endocrinologist, will also be joining for the Q&A portion.

謝謝您，接線生。大家下午好，感謝大家加入我們討論 2025 年第一季的業績。今天參加電話會議的是創始人兼首席執行官 Scott Struthers 博士；首席醫療和發展官 Dana Pizzuti 博士；伊莎貝爾·卡洛福諾斯 (Isabel Kalofonos)，首席商務官；以及首席財務官 Toby Schilke；首席內分泌學家 Alan Krasner 博士也將參加問答環節。

Please note, there is a slide deck for today's presentation, which is in the Events and Presentations section of the Investor's page on the Crinetics website. In addition, a press release was issued earlier today and is also available on the corporate website.

請注意，今天的簡報有一個幻燈片，位於 Crinetics 網站投資者頁面的「活動和簡報」部分。此外，今天早些時候發布了一份新聞稿，也可在公司網站上查閱。

Slide 2, as a reminder, we will be making forward-looking statements, and I invite you to learn more about the risks and uncertainties associated with these statements as disclosed in our SEC filings. Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's news release. the company's other news releases and Crinetics' SEC filings, including its annual report on Form 10-K and quarterly reports on Form 10-Q.

投影片 2，提醒一下，我們將做出前瞻性陳述，我邀請您詳細了解我們在美國證券交易委員會 (SEC) 文件中揭露的與這些陳述相關的風險和不確定性。此類前瞻性陳述並非績效保證，由於與本公司業務相關的風險和不確定性，本公司的實際結果可能與此類陳述中明示或暗示的結果有重大差異。這些前瞻性陳述完全受到今天新聞稿中的警示性聲明的限制。該公司的其他新聞稿和 Crinetics 的 SEC 文件，包括其 10-K 表年度報告和 10-Q 表季度報告。

I would also like to specify that the content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, May 8, 2025. Crinetics takes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call.

我還想指出，本次電話會議的內容包含時間敏感信息，這些信息僅截至本次直播之日，即 2025 年 5 月 8 日是準確的。Crinetics 不承擔修改或更新任何前瞻性陳述以反映本次電話會議日期之後的事件或情況的義務。

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

說完這些，我就把電話交給史考特。

Thank you, Gayathri, and good afternoon to everyone joining in today's call. We're pleased to share our first quarter results and highlight the great progress we're making towards our mission of transforming the lives of patients with serious endocrine and endocrine adjacent diseases.

謝謝你，Gayathri，祝今天參加電話會議的各位下午好。我們很高興分享我們的第一季業績，並強調我們在改變嚴重內分泌和內分泌相關疾病患者生活的使命方面取得的巨大進展。

Turning to slide 3. Crinetics has never been stronger, and I want to emphasize that. We're strategically positioned for long-term sustainable growth. Our immediate focus is on the anticipated commercial launch of our first product this year. This is a pivotal milestone for the company. We believe paltusotine has the potential to deliver meaningful improvements for people living with acromegaly.

翻到幻燈片 3。Crinetics 從未如此強大，我想強調這一點。我們的策略定位是實現長期可持續成長。我們的當務之急是今年推出我們第一款產品的商業版本。這對公司來說是一個關鍵的里程碑。我們相信帕妥索汀有潛力為肢端肥大症患者帶來有意義的改善。

Backed by an experienced team deeply embedded in the endocrinology community and driven by a strong commitment to patients and science, we're well on our way to becoming a fully integrated global commercial organization. We're advancing a robust pipeline, in parallel, including 2 late-stage candidates, recently clearing IND and 3 additional candidates in preclinical studies.

在一支深耕內分泌學界的經驗豐富的團隊的支持下，在對患者和科學的堅定承諾的推動下，我們正朝著成為一個完全整合的全球商業組織的道路上邁進。我們正在同時推進強大的產品線建設，其中包括 2 個後期候選藥物（最近已批准 IND）和 3 個處於臨床前研究中的另外候選藥物。

With $1.3 billion on the balance sheet, we're able to continue to invest in our pipeline, support prospective launches and thoughtfully pursue opportunities that enhance value across our portfolio. We have never been stronger.

憑藉 13 億美元的資產負債表，我們能夠繼續投資於我們的產品線，支持未來的產品發布，並深思熟慮地尋求提升我們整個投資組合價值的機會。我們從未如此強大。

I'd like to take a moment to welcome Toby Schilke, who you'll be hearing from towards the end of today's call. Toby recently joined as Chief Financial Officer, and he brings over 25 years of global experience with a proven track record of guiding companies through the transition from R&D-focused ventures into fully integrated commercial organizations. Toby's extensive financial and operational experience will be invaluable as we accelerate our growth trajectory and position Crinetics for long-term success.

我想花點時間歡迎 Toby Schilke，在今天的電話會議結束時您將聽到他的演講。Toby 最近加入公司擔任財務官，他擁有超過 25 年的全球經驗，在指導公司從以研發為重點的企業轉型為完全整合的商業組織方面有著良好的記錄。隨著我們加速成長軌跡並使 Crinetics 獲得長期成功，Toby 豐富的財務和營運經驗將發揮無價的作用。

I also wanted to reassure you that regulatory engagement with the FDA and paltusotine NDA for acromegaly as well as our other clinical development activities have been proceeding on track. We're grateful for the ongoing professionalism and commitment of the staff at FDA with whom we interact. We remain proactive in monitoring the evolving regulatory environment, and maintaining active dialogue with key stakeholders, both in the administration and on Capitol Hill.

我還想向您保證，與 FDA 的監管合作以及用於治療肢端肥大症的 paltusotine NDA 以及我們的其他臨床開發活動一直在按計劃進行。我們感謝與我們互動的 FDA 員工的持續專業和奉獻精神。我們將繼續積極監控不斷變化的監管環境，並與政府和國會山莊的主要利益相關者保持積極對話。

As you'll hear from Isabel, we're laser-focused on preparing for the anticipated launch of paltusotine in September. This will be our first product approval and a defining milestone for our ambition to become a fully integrated pharmaceutical company. On today's call, we'll walk through some of the launch initiatives we are executing and reflect on the progress the team has made to date.

正如伊莎貝爾所說，我們正全神貫注地為預計在九月推出的 paltusotine 做準備。這將是我們的首個產品獲批，也是我們成為完全一體化製藥公司的宏偉目標的決定性里程碑。在今天的電話會議上，我們將介紹我們正在執行的一些啟動計劃，並回顧團隊迄今為止的進展。

Turning to atumelnant. We remain very encouraged by its potential to establish an uncompromising treatment goal for people living with congenital adrenal hyperplasia. We're moving forward with a Phase III study for adults with CAH that Dana will describe in some detail. At a high level, this study is designed to redefine the standard of care as the achievement of normal adrenal androgen levels with only physiologic levels of glucocorticoid replacement. We believe atumelnant should be used to treat the disease and glucocorticoid should only be used for physiologic replacement, not treatment.

轉向 atumelnant。我們仍然對其為患有先天性腎上腺增生症的人建立不妥協的治療目標的潛力感到非常鼓舞。我們正在針對患有 CAH 的成年人進行第三階段研究，Dana 將對此進行詳細描述。從高層次上講，這項研究旨在將治療標準重新定義為僅透過生理層面的糖皮質激素替代即可達到正常的腎上腺雄激素水平。我們認為應使用 atumelnant 來治療該疾病，而糖皮質激素僅應用於生理替代，而不是治療。

With that, I'll hand the call over to Isabel to update on our acromegaly launch preparations. Isabel?

說完這些，我將把電話交給伊莎貝爾，讓她報告我們的肢端肥大症發射準備。伊莎貝爾？

Thanks, Scott. As described on slide 4, our mission with paltusotine is to provide the next generation of care for people living with acromegaly. While we have a long-term global vision, and we are building out our infrastructure to support commercialization of our whole pipeline, we are currently focused on executing on the anticipated U.S. launch.

謝謝，斯科特。如同幻燈片 4 所述，我們對 paltusotine 的使命是為肢端肥大症患者提供下一代護理。雖然我們有一個長期的全球願景，並且我們正在建立基礎設施以支持我們整個管道的商業化，但我們目前專注於執行預期的美國發布。

We are making significant progress in building our infrastructure, educating and driving awareness among health care professionals and patients, and engaging with payers. We also have a strong long-standing patient advocacy partnerships in place as we continue to engage with the broader acromegaly community.

我們在建立基礎設施、教育和提高醫療保健專業人員和患者的意識以及與付款人的接觸方面取得了重大進展。我們也建立了長期且強大的患者倡議夥伴關係，並繼續與更廣泛的肢端肥大症社群接觸。

On the health care professional side, we have held advisory boards with nurses and endocrinologists, and they have provided positive feedback on the potential value proposition of paltusotine in both biochemical control of IGF-1 and symptom control. We are working on the final sales force mapping, and we expect to have approximately 30 reps in place over the summer.

在醫療保健專業人士方面，我們與護理師和內分泌學家組成了顧問委員會，他們對帕妥索汀在 IGF-1 生化控制和症狀控制方面的潛在價值主張提供了積極的反饋。我們正在製定最終的銷售隊伍規劃，預計今年夏天將有大約 30 名銷售代表到位。

We will cover health care professionals in pituitary treatment centers, academic centers of excellence and in community endocrinology practices. We are making powerful strides in advancing awareness and visibility for paltusotine and our broader pipeline at conference attended by academic endocrinologists like ENDO and by community endocrinologists like ACE. We will share exciting new scientific data that reinforce the long-term value of paltusotine and the need for innovation in acromegaly treatment.

我們將涵蓋腦下垂體治療中心、卓越學術中心和社區內分泌實踐中的醫療保健專業人員。我們正在大力提高帕妥索汀和我們更廣泛的產品線在 ENDO 等學術內分泌學家和 ACE 等社區內分泌學家參加的會議上的知名度和可見度。我們將分享令人興奮的新科學數據，以強化帕妥索汀的長期價值以及肢端肥大症治療創新的必要性。

Notably, we'll present data from our 4-year optional open-label extension or OLE study. Demonstrating that patients on paltusotine maintain biochemical control in IGF-1 over a 96-week period. Equally important, 87% of patients prefer paltusotine over prior injectable SRL therapy, highlighting the patient-centric benefits of our once-daily oral treatment.

值得注意的是，我們將展示我們為期 4 年的可選開放標籤擴展或 OLE 研究的數據。證明服用帕妥索汀的患者在 96 週內維持 IGF-1 的生化控制。同樣重要的是，87% 的患者更喜歡使用 paltusotine 而不是先前的注射 SRL 療法，這凸顯了我們每日一次口服治療的以患者為中心的優勢。

We will also share real-world evidence that current SRL therapies are associated with persistent breakthrough symptoms and low compliance and adherence. Patients experience symptom exacerbations more than one-third of days each month, and those days are not always concentrated in the weeks leading up to the next injection.

我們也將分享現實世界的證據，證明目前的 SRL 療法與持續的突破性症狀以及低依從性和依從性有關。患者每月有超過三分之一的時間會出現症狀加重，而且這些日子並不總是集中在下次注射前的幾週內。

Data from PATHFNDR-1 demonstrates that patients treated with paltusotine experienced decreased symptom exacerbation rates over time. Additionally, based on real-world data compiled over a 4-year period, 80% of patients with acromegaly who are newly treated either discontinue or switch from their initial treatment within their first year. This data highlights paltusotine's scientific and clinical relevance in an area of significant unmet need to improve the lives of patients living with acromegaly.

PATHFNDR-1 的數據表明，接受帕妥索汀治療的患者的症狀惡化率隨著時間的推移而降低。此外，根據 4 年來收集的真實世界數據，80% 接受新治療的肢端肥大症患者在第一年內停止治療或改變治療方案。這些數據凸顯了帕妥索汀在改善肢端肥大症患者生活這一尚未滿足的重大需求領域的科學和臨床相關性。

On slide 5, education and awareness are critical elements of our plan to reach patients as part of our activate, adopt, access, adhere launch strategy. We are focused on elevating awareness of the burden of disease experienced by patients, even those currently being treated. Our insights consistently show that while patients might achieve biochemical control, they often continue to experience persistent symptoms that impact quality of life.

在第 5 張投影片上，教育和意識是我們接觸病患計畫的關鍵要素，也是我們啟動、採用、存取、堅持啟動策略的一部分。我們致力於提高人們對患者（甚至是正在接受治療的患者）所承受的疾病負擔的認識。我們的見解始終表明，儘管患者可能實現生化控制，但他們通常會繼續經歷影響生活品質的持續症狀。

Our educational initiatives are designed to address both aspects of disease control to ensure patients are better informed, more empowered and fully activated to advocate for treatment that addresses the unmet need of the current standard of care.

我們的教育措施旨在解決疾病控制的兩個方面，以確保患者能夠更好地了解情況、更有權力、更充分地倡導治療，以滿足當前標準護理中未滿足的需求。

We recently launched our CrinetiCARE patient support service platform to act as a partner to patients on their treatment journey from the very beginning. We opened our hub before the anticipated approval because the acromegaly community faces significant unmet need in patient support. CrinetiCARE connects patients with nurses to discuss their symptoms and offers interactive tools to help them locate experience health care providers. The CrinetiCARE platform will serve as a continuous connection between us and the patients we serve. Once paltusotine is approved, CrinetiCARE will provide a white glove experience for patients from the time they receive prescriptions to initiation of therapy, all the way to long-term maintenance.

我們最近推出了 CrinetiCARE 病患支援服務平台，從一開始就成為病患治療過程中的合作夥伴。我們在預期批准之前開設了我們的中心，因為肢端肥大症患者群體在患者支持方面面臨巨大的未滿足需求。CrinetiCARE 將患者與護理人員聯繫起來討論他們的症狀，並提供互動式工具來幫助他們找到經驗豐富的醫療保健提供者。CrinetiCARE 平台將成為我們與我們服務的患者之間的持續連結。一旦帕妥索汀獲得批准，CrinetiCARE 將為患者提供從收到處方到開始治療直至長期維持的全程白手套治療體驗。

We also recently revealed our unbranded disease state education campaign. This campaign leveraged our learnings from our ongoing engagement with health care professionals, patients and acromegaly community partners to amplify patients' voices and provide educational materials.

我們最近也推出了無品牌疾病狀態教育活動。這項活動利用我們與醫療保健專業人員、患者和肢端肥大症社區合作夥伴持續接觸的經驗，擴大患者的聲音並提供教育材料。

Turning to slide 6. We continue our preapproval conversations with payers, and we are encouraged by their feedback. In particular, we anticipate that prior authorization for paltusotine will reflect the label, which will help us drive the success of reimbursement. Paltusotine value proposition is resonating with payers because the unmet need with injectable SRL, long titration times, incorrect injections and inconsistent symptom control collectively result in higher cost overall.

翻到幻燈片 6。我們繼續與付款人進行預先批准對話，他們的回饋令我們感到鼓舞。特別是，我們預計帕妥索汀的事先授權將反映該標籤，這將有助於我們推動報銷的成功。Paltusotine 的價值主張引起了付款人的共鳴，因為注射 SRL 的未滿足需求、較長的滴定時間、不正確的注射和不一致的症狀控制共同導致了總體成本的增加。

First, patients starting on SRLs typically have their dose titrated every 3 months. With 3 different dose strengths available, it might take patients up to 9 months to get to the right dose where the disease is under control. Payers bear the cost of treatment for many months before the patient sees a benefit. In contrast, daily dosing of paltusotine will allow titration to the optimal levels within weeks if titration is needed.

首先，開始服用 SRL 的患者通常每 3 個月調整一次劑量。由於有 3 種不同劑量可供選擇，患者可能需要長達 9 個月的時間才能達到控制病情的正確劑量。在患者看到療效之前，付款人必須承擔數月的治療費用。相反，如果需要滴定，每日服用帕妥索汀可以在幾週內達到最佳水平。

Second, SRLs are not always correctly delivered, which can lead to higher cost to manage the resulting symptoms and side effects. For context, SRL injections are given with a large 18, 19 gauge needle. The injections are unpleasant to receive and challenging to give.

其次，SRL 並非總是能夠正確輸送，這會導致處理由此產生的症狀和副作用的成本更高。就上下文而言，SRL 注射採用較大的 18、19 號針頭進行。注射的過程令人不快，而且注射起來也很困難。

A recent research conducted at MD Anderson, one of the leading centers, found that half of long-acting octreotide injections administered by experienced nurses were not injected into the intramuscular space. The depot of octreotide instead persisted in the subcutaneous layer where they form nodules that sometimes became granula. It is important to note that if the drug is not administered properly, it might not achieve its intended efficacy.

領先的醫療中心之一 MD Anderson 最近進行的一項研究發現，由經驗豐富的護士注射的長效奧曲肽有一半沒有註射到肌肉內。奧曲肽的儲存庫反而停留在皮下層，在那裡形成結節，有時變成顆粒。值得注意的是，如果藥物使用不當，可能無法達到預期的療效。

In addition, payers understand that injectable SRLs often do not provide adequate disease control for the duration of an injection cycle. According to our real-world data analysis, one-third of acromegaly patients on injectable SRL received more than the 13 injections per year expected based on an approved dosing, which is every 4 weeks. Consequently, this increases cost substantially for payers. Furthermore, uncontrolled acromegaly is associated with comorbidities and additional procedures, which are costly for payers and very burdensome for patients. Lastly, paltusotine once-daily oral dosing offers an opportunity to improve patient adherence for more consistent control.

此外，付款人明白注射用 SRL 通常無法在註射週期內提供足夠的疾病控制。根據我們的真實世界數據分析，三分之一的接受注射 SRL 的肢端肥大症患者每年接受的注射次數超過了根據批准劑量（每 4 週一次）預期的 13 次注射。因此，這大大增加了付款人的成本。此外，不受控制的肢端肥大症與合併症和額外手術有關，這對付款人來說成本高昂，對患者來說負擔也很重。最後，每日一次口服帕妥索汀可以提高患者的依從性，從而實現更一致的控制。

In sum, there remains a significant unmet need for safe, highly efficacious, easy-to-administer treatments that offer daily control. And the economic and clinical value that an option like paltusotine could provide to all stakeholders is clear. These and other market insights continue to highlight meaningful unmet need in acromegaly and a strong enthusiasm for paltusotine. During early launch, we anticipate measured uptake as we educate both health care providers and patient communities.

總而言之，對於安全、高效、易於管理且能夠進行日常控制的治療方法仍然存在很大的未滿足需求。而像帕妥索汀這樣的選擇可以為所有利害關係人提供的經濟和臨床價值是顯而易見的。這些和其他市場洞察繼續凸顯了肢端肥大症領域尚未滿足的重要需求以及對帕妥索汀的強烈熱情。在早期發布期間，我們預計在教育醫療保健提供者和患者社區的過程中，會出現適度的吸收。

As with any new therapy, we expect coverage to build progressively, and we will work through the formulary review process with payers over the first 6 to 9 months. Our team is highly prepared and confident in navigating these initial steps to unlock the full opportunity of paltusotine.

與任何新療法一樣，我們預計覆蓋範圍將逐步擴大，並且我們將在前 6 到 9 個月內與付款人一起完成處方審查流程。我們的團隊已做好充分準備，並有信心完成這些初步步驟，以充分發揮帕妥索汀的潛力。

As the value proposition continues to resonate with patients, health care professionals and payers, we are optimistic that over time, paltusotine could become the new standard of care in acromegaly.

隨著價值主張繼續引起患者、醫療保健專業人員和付款人的共鳴，我們樂觀地認為，隨著時間的推移，帕妥索汀可能成為肢端肥大症治療的新標準。

And now Dana will share a regulatory update and additional detail on our CAH late-stage development strategy. Dana?

現在，Dana 將分享監管更新以及有關我們的 CAH 後期開發策略的更多細節。戴娜？

Thank you, Isabel. Starting with paltusotine, we continue to make progress in both the U.S. and EU, where our regulatory reviews remain on track. We have not experienced any disruptions with our interactions with the FDA and continue to expect a decision by September 25th. And as previously mentioned, we do not anticipate an advisory committee meeting as part of the NDA review.

謝謝你，伊莎貝爾。從帕妥索汀開始，我們在美國和歐盟都不斷取得進展，我們的監管審查仍在按計劃進行。我們與 FDA 的互動沒有遇到任何中斷，並將繼續期待在 9 月 25 日之前做出決定。如同前面提到的，我們預計在 NDA 審查過程中不會召開諮詢委員會會議。

The European Medicines Agency has validated our MAA submission and granted orphan drug designation. We believe the orphan drug designation highlights the unmet need in acromegaly and the potential benefit that paltusotine can offer patients compared to existing therapies. Our team continues to work with regulatory authorities in the U.S. and EU on all aspects of the review process.

歐洲藥品管理局已驗證我們的MAA提交並授予孤兒藥資格。我們相信，孤兒藥資格認定凸顯了肢端肥大症領域尚未滿足的需求，以及與現有療法相比，帕妥索汀可以為患者帶來的潛在益處。我們的團隊將繼續與美國和歐盟的監管機構就審查過程的各個方面進行合作。

In preparation for launch, our growing medical affairs team has been connecting with the endocrinology community. Our experienced endocrinologists at Crinetics have been making warm introductions for our medical sites liaisons to all the top KOLs. We've hosted roundtable discussions to deepen our understanding of the patient journey and gaps in treatment. As Isabel highlighted, we have submitted multiple abstracts to upcoming endocrinology meetings that showcase paltusotine's differentiation.

為了準備發布，我們不斷成長的醫療事務團隊一直與內分泌學界保持聯繫。Crinetics 經驗豐富的內分泌學家一直在熱情地向我們的醫療站點聯絡員介紹所有頂級 KOL。我們舉辦了圓桌討論會，以加深對患者治療歷程和治療差距的了解。正如伊莎貝爾所強調的，我們已經向即將召開的內分泌學會議提交了多份摘要，展示了帕妥索汀的差異化。

Moving to carcinoid syndrome. We expect to initiate the CAREFNDR Phase III trial in the second half of 2025.

轉向類癌症候群。我們預計 2025 年下半年啟動 CAREFNDR 第三階段試驗。

Turning to atumelnant on slide 7. We added a fourth cohort to our Phase II study due to the significant amount of enthusiasm and interest from sites and investigators. Cohort 4 is just one part of our larger development plan for atumelnant in CAH, and it is an exploratory analysis in a small group of 6 to 12 patients to evaluate 80 milligrams with morning dosing as opposed to evening dosing in the prior cohorts and to allow for glucocorticoid reduction.

前往幻燈片 7 上的 atumelnant。由於來自各個站點和研究人員的極大熱情和興趣，我們在第二階段研究中增加了第四個隊列。隊列 4 只是我們針對 CAH 的 atumelnant 更大開發計劃的一部分，它是對 6 至 12 名患者的小組進行的探索性分析，以評估早晨服用 80 毫克（而非之前隊列中的晚上服用）的情況，並允許減少糖皮質激素。

As previously shared, we are also conducting an open-label extension study, which will provide real-world insights into atumelnant's efficacy and safety over the long term. Investigators will have the opportunity to titrate both the dose of atumelnant and the dose of GCs as they see fit. Study participants from the Phase II study are given the opportunity to enroll in the OLE. This study is ongoing and will eventually also include patients who complete Phase III.

如同先前所分享的，我們也正在進行一項開放標籤擴展研究，這將為 atumelnant 的長期功效和安全性提供真實世界的見解。研究人員將有機會根據自己的需求調整 atumelnant 和 GC 的劑量。第二階段研究的參與者有機會參與 OLE。這項研究仍在進行中，最終還將包括完成第三階段的患者。

Turning to slide 8. Our Phase III study for atumelnant in adult CAH patients builds on the strong top line results we shared from cohorts 1 through 3 of the Phase II study. It is designed to provide a potential new therapeutic paradigm for patients. As Scott mentioned, there is a significant need for new treatments in CAH that not only allow patients to lower their GC dose to physiologic levels, but also to control their androgens, which account for many of the signs and symptoms of the underlying disease.

翻到幻燈片 8。我們針對成年 CAH 患者進行的 atumelnant III 期研究建立在我們分享的 II 期研究第 1 至第 3 組患者的強勁頂線結果的基礎上。其旨在為患者提供一種潛在的新治療模式。正如斯科特所提到的，CAH 迫切需要新的治療方法，不僅可以讓患者將 GC 劑量降低到生理水平，還可以控制他們的雄激素，雄激素是造成許多潛在疾病的體徵和症狀的原因。

With this in mind, we are pursuing a novel primary endpoint that combines both goals. The proportion of participants with A4 levels less than or equal to the upper limit of normal and who are on physiologic doses of GC replacement at week 32. Patients should not have to sacrifice one or the other in treating CAH.

考慮到這一點，我們正在追求一個結合這兩個目標的新穎的主要終點。在第 32 週時 A4 水準小於或等於正常上限且接受生理劑量 GC 替代治療的參與者比例。患者在治療 CAH 時不應該犧牲其中一種治療手段。

In this study, we will enroll 150 participants who will be treated for 32 weeks. We will offer investigators 2 periods of time over which they can reduce GCs with 4 assessment visits in each period. Investigators are given additional flexibility for physician-guided reductions. We designed this individualized approach in response to feedback we received from investigators, who prefer to use their discretion in titrating GCs as they would in a real-world scenario with the goal of reaching physiologic doses.

在這項研究中，我們將招募 150 名參與者，接受 32 週的治療。我們將為研究人員提供 2 個時間段，每個時間段內他們可以進行 4 次評估訪問來減少 GC。研究人員可以更靈活地根據醫生的指導減少劑量。我們根據研究人員的回饋設計了這種個人化方法，他們更喜歡像在現實世界中一樣自行決定滴定 GC，以達到生理劑量。

Based on the early and profound decrease in A4 seen without atumelnant treatment in the Phase II study, we are measuring A4 at just 2 weeks after the study initiation and allowing investigators to assess glucocorticoid reduction immediately thereafter.

根據 II 期研究中未接受 atumelnant 治療時觀察到的 A4 早期大幅下降情況，我們在研究開始後僅 2 週就對 A4 進行了測量，以便研究人員在此之後立即評估糖皮質激素的減少情況。

Midway through the study, participants will be on stable GC doses for several weeks, so their A4 can be measured. Investigators will then have the option to titrate patients up to 120-milligram dose of atumelnant if the patient needs more A4 control. Otherwise, participants will continue on 80 milligrams. The key secondary and other endpoints are designed to demonstrate potential benefits beyond what has been achieved with existing standard of care for CAH patients.

在研究進行到中期時，參與者將服用穩定劑量的 GC 數週，以便測量他們的 A4。如果患者需要更多的 A4 控制，研究人員可以選擇將患者的 atumelnant 劑量滴定至 120 毫克。否則，參與者將繼續服用 80 毫克。關鍵的次要終點和其他終點旨在展示超越 CAH 患者現有護理標準所取得的潛在益處。

In addition to reductions in key disease biomarkers such as A4 and 17-OHP and other androgens, we will study improvement in the clinical signs and symptoms of CAH, including, but not limited to, restoration of menses, testicular adrenal rest tumors or TARTs and adrenal size.

除了減少 A4 和 17-OHP 以及其他雄性激素等關鍵疾病生物標記外，我們還將研究 CAH 臨床體徵和症狀的改善，包括但不限於月經的恢復、睪丸腎上腺殘餘腫瘤或 TART 和腎上腺大小。

Our primary endpoint will use morning androgen measurement post GC dosing, consistent with the previous regulatory precedent. However, in our secondary endpoints, measuring these hormone levels pre-GC dosing is a rigorous test of efficacy because the androgen levels can be influenced by morning GC administration. Consistent with our patient-centric approach to drug development, we will include a novel disease-specific patient-reported outcomes tool as part of the study design.

我們的主要終點將使用 GC 給藥後的早晨雄激素測量，這與先前的監管先例一致。然而，在我們的次要終點中，測量 GC 給藥前的這些荷爾蒙水平是對療效的嚴格測試，因為雄性激素水平會受到早晨 GC 給藥的影響。與我們以患者為中心的藥物開發方法一致，我們將在研究設計中加入一種針對特定疾病的新型患者報告結果工具。

The last piece of our CAH development program is the combined Phase II/III study in pediatric patients. We are finalizing our specific plans for integrating each age group into the registrational study, and we have already received helpful feedback from FDA and European authorities on our proposed study design.

我們的 CAH 開發計劃的最後一部分是針對兒科患者的 II/III 期聯合研究。我們正在敲定將每個年齡組納入註冊研究的具體計劃，並且我們已經收到了來自 FDA 和歐洲當局對我們提出的研究設計的有益反饋。

In summary, as illustrated on slide 9, we believe atumelnant has the potential to establish uncompromising treatment goals for people living with CAH, by addressing both elevated androgens and reducing the need for supraphysiologic glucocorticoid dosing, which could lead to negative side effects for patients. We believe glucocorticoids should ideally only be used to provide physiologic replacement, not to treat the underlying disease.

總之，如幻燈片 9 所示，我們相信 atumelnant 有潛力為 CAH 患者建立不妥協的治療目標，透過解決雄激素升高的問題並減少對超生理糖皮質激素劑量的需求，這可能會給患者帶來負面副作用。我們認為，糖皮質激素最好只用於提供生理替代，而不是治療潛在疾病。

Our Phase III trial aims to provide a tailored approach to treatment for individual patients, enroll a broad patient population, inclusive of patients who could benefit from GC normalization, androgen normalization or both, and measure clinical outcomes that are paramount to both HCPs and patients. Our vision is to lower the burden of disease overall and provide a new standard of care for the 17,000-plus people living with CAH.

我們的 III 期試驗旨在為個別患者提供量身定制的治療方法，招募廣泛的患者群體，包括可以從 GC 正常化、雄激素正常化或兩者中受益的患者，並衡量對 HCP 和患者都至關重要的臨床結果。我們的願景是降低整體疾病負擔，並為 17,000 多名 CAH 患者提供新的護理標準。

Moving to slide 10. We are making steady progress on the rest of our pipeline, and we are pleased to announce IND clearance for 9682, the first candidate from our non-peptide drug conjugate or NDC platform. 9682 is being studied for SST2 positive tumors, including neuroendocrine tumors or NETs, to complement our carcinoid syndrome indication with paltusotine. Additionally, our discovery team continues to identify new ways to leverage the NDC platform for novel targets to address unmet needs in endocrine oncology.

移至投影片 10。我們在其餘研發線上也取得了穩定進展，並且很高興地宣布 9682 獲得 IND 批准，這是我們非肽類藥物偶聯物或 NDC 平台的首個候選藥物。 9682 正在針對 SST2 陽性腫瘤（包括神經內分泌腫瘤或 NET）進行研究，以補充我們對帕妥索汀的類癌症候群適應症。此外，我們的發現團隊繼續尋找新方法利用 NDC 平台尋找新目標來解決內分泌腫瘤學中未滿足的需求。

As mentioned in our press release, IND-enabling studies for the TSH antagonist are continuing as expected. Also, we continue to progress our SST3 agonist candidate. Based on emerging data from IND-enabling studies, our PTH antagonist candidate preclinical development has been substituted with another candidate expected to exhibit an improved profile. This new candidate is in IND-enabling studies, which we intend to complete next year. This decision is reflective of the rigorous process we followed with paltusotine and atumelnant and that we apply to all our pipeline programs.

正如我們在新聞稿中提到的，TSH 拮抗劑的 IND 支持研究正在按預期繼續進行。此外，我們也持續推進我們的 SST3 激動劑候選藥物。根據 IND 支持研究的新數據，我們的 PTH 拮抗劑候選藥物臨床前開發已被另一種預計會表現出更好特性的候選藥物所取代。這位新候選人正在進行 IND 支持研究，我們計劃明年完成。這項決定體現了我們在 paltusotine 和 atumelnant 方面所遵循的嚴格流程，並且我們將其應用於所有管道項目。

We look forward to highlighting our early-stage pipeline in more detail at our upcoming R&D Day on June 26. Of note, we will cover NET and beyond with 9682 for SST2 expressing tumors and paltusotine for carcinoid syndrome. We will also present our TSH antagonist for Graves, a thyroid eye disease and our SST3 agonist for ADPKD. These programs represent the next generation of Crinetics innovation and have the potential to positively impact the lives of patients and their caregivers across multiple communities.

我們期待在 6 月 26 日即將舉行的研發日上更詳細地介紹我們的早期產品線。值得注意的是，我們將涵蓋 NET 及其他領域，其中 9682 用於治療 SST2 表達腫瘤，paltusotine 用於治療類癌症候群。我們還將介紹用於治療格雷夫茲病（一種甲狀腺眼疾）的 TSH 拮抗劑和用於治療 ADPKD 的 SST3 激動劑。這些計畫代表了 Crinetics 的下一代創新，並有可能對多個社區的患者及其照護者的生活產生積極影響。

With that, Toby will now provide the financial update.

現在，托比將提供財務更新資訊。

Thank you, Dana. Turning to slide 11. I am pleased to be participating in my first earnings call at Crinetics. It is a privilege to join a team with a patient-centric mission and leading-edge science. We are poised for growth, and importantly, well capitalized to execute on our ambition.

謝謝你，達娜。翻到第 11 張投影片。我很高興參加 Crinetics 的第一次財報電話會議。我很榮幸能夠加入以病人為中心、擁有尖端科學的團隊。我們已準備好實現成長，而且重要的是，我們擁有充足的資金來實現我們的目標。

Now I will present the financial results for the first quarter of 2025. I will not read aloud the full results as they are available in our press release and on our Form 10-Q filing. Beginning with our income statement, we recognized $0.4 million of revenue during the first quarter of 2025 compared to $0.6 million during the same period in 2024. As a reminder, this revenue is noncash and is based on amortization of payments we received in connection with our paltusotine licensing arrangement with our Japanese partner, SKK.

現在我將介紹2025年第一季的財務表現。我不會大聲宣讀完整的結果，因為它們已在我們的新聞稿和 10-Q 表格文件中公佈。從我們的損益表開始，我們在 2025 年第一季確認了 40 萬美元的收入，而 2024 年同期為 60 萬美元。提醒一下，這筆收入是非現金的，是基於我們與日本合作夥伴 SKK 達成的 paltusotine 許可協議所收到的付款的攤銷。

Our research and development expenses in the first quarter of 2025 were $76.2 million, a 43% increase compared to the same period in 2024. Excluding depreciation, amortization and stock-based compensation, R&D expense was $64.4 million. The increase in R&D expenses was primarily due to additional personnel, increased manufacturing costs and higher outside services costs to advance our clinical programs and expand our preclinical portfolio. We expect quarterly R&D spend to increase sequentially through the remainder of the year, primarily driven by Phase III clinical trials for paltusotine and atumelnant.

我們 2025 年第一季的研發費用為 7,620 萬美元，與 2024 年同期相比成長了 43%。不包括折舊、攤提和股票薪酬，研發費用為 6,440 萬美元。研發費用的增加主要是由於為推進我們的臨床項目和擴大我們的臨床前產品組合而增加的人員、增加的製造成本和更高的外部服務成本。我們預計，今年剩餘時間內季度研發支出將季比增加，主要受 paltusotine 和 atumelnant 的 III 期臨床試驗推動。

Our selling, general and administrative expenses for the first quarter of 2025 were $35.5 million, a 71% increase compared to the same period in 2024. Excluding depreciation, amortization and stock-based compensation, SG&A expense was $26.2 million. The increase in SG&A expense was primarily driven by growth to support our ongoing programs and the planned commercial launch of paltusotine. We expect quarterly SG&A investment to increase sequentially through the remainder of the year as we continue to build our commercial infrastructure and prepare for the anticipated launch of paltusotine.

我們 2025 年第一季的銷售、一般和行政費用為 3,550 萬美元，與 2024 年同期相比成長了 71%。不包括折舊、攤提和股票薪酬，銷售、一般及行政費用為 2,620 萬美元。銷售、一般及行政費用的增加主要是為了支持我們正在進行的項目和計劃中的 paltusotine 商業發布。隨著我們繼續建造商業基礎設施並為預計推出的 paltusotine 做準備，我們預計今年剩餘時間內季度銷售、一般及行政費用 (SG&A) 投資將環比增加。

Our cash used in operations for the 3 months ending March 31, 2025, was $88.5 million compared to $52.9 million for the same period in 2024. For 2025, we continue to anticipate our cash used in operations to be between $340 million and $380 million. This compares to $226 million of cash used in operations in 2024. Approximately 60% of the increase relative to 2024 is due to R&D investments, with the balance due to SG&A.

截至 2025 年 3 月 31 日的 3 個月，我們的營運現金使用量為 8,850 萬美元，而 2024 年同期為 5,290 萬美元。到 2025 年，我們預計營運現金流將在 3.4 億美元至 3.8 億美元之間。相比之下，2024 年營運中使用的現金為 2.26 億美元。與 2024 年相比，約 60% 的成長來自研發投資，其餘成長來自銷售、一般及行政費用。

Turning to slide 12. We ended the first quarter of 2025 on strong financial footing with approximately $1.3 billion in cash, cash equivalents and investments, which we continue to expect to fund our operations into 2029. As a reminder, we could potentially receive up to $250 million, if Lilly exercises its option to acquire Radionetics.

翻到第 12 張投影片。截至 2025 年第一季度，我們的財務狀況良好，擁有約 13 億美元的現金、現金等價物和投資，我們預計這些資金將繼續為我們到 2029 年的營運提供資金。提醒一下，如果禮來公司行使其收購 Radionetics 的選擇權，我們可能會獲得高達 2.5 億美元的資金。

Crinetics has always been disciplined with capital allocation, and we continue to take a prudent approach to execute on the compelling opportunities ahead of us. We believe our strong balance sheet positions us to deliver on our near-term milestones, including the anticipated approval and launch of paltusotine and advance our deep and rich pipeline in parallel.

Crinetics 始終嚴格執行資本配置，我們將繼續採取審慎的方式來抓住我們面前的誘人機會。我們相信，我們強勁的資產負債表使我們能夠實現近期的里程碑，包括預期的 paltusotine 的批准和推出，並同時推進我們深度和豐富的管道。

I'll now turn it over to Scott for closing remarks. Scott?

現在我將把發言時間交給史考特，請他作最後發言。史考特？

Thank you, Toby. Moving on to slide 13. At Crinetics, our core mission is to improve patients' lives and transform the treatment paradigm in areas of serious unmet need like acromegaly. For over 10 years, we have partnered with patients for their direct input on our discovery effort, clinical designs and patient resources.

謝謝你，托比。移至幻燈片 13。在 Crinetics，我們的核心使命是改善患者的生活並改變肢端肥大症等嚴重未滿足需求領域的治療模式。十多年來，我們一直與患者合作，讓他們直接參與我們的發現工作、臨床設計和患者資源。

We design our therapies to allow patients to live their best lives instead of letting their disease define them. With our strong pipeline of late and early-stage candidates and the support of our robust balance sheet, we are well positioned to deliver on our clinical, regulatory and commercial priorities in 2025 and beyond.

我們設計的治療方法是讓患者過最好的生活，而不是讓疾病定義他們。憑藉我們強大的後期和早期候選藥物儲備以及穩健的資產負債表的支持，我們有能力在 2025 年及以後實現我們的臨床、監管和商業優先事項。

With that, I'll hand the call back to the operator to begin the Q&A. Please limit yourselves to one question each in the interest of time. Operator?

說完這些，我將把電話交還給接線員，開始問答。為了節省時間，請每個人只問一個問題。操作員？

Thank you, Scott. (Operator Instrcutions)

謝謝你，斯科特。（操作員指令）

Yasmeen Rahimi with Piper Sandler.

亞斯明‧拉希米 (Yasmeen Rahimi) 與派珀‧桑德勒 (Piper Sandler)。

Two quick questions. The first question is, could you talk about the powering of your very innovative primary endpoint, which is a co-primary? And then short question for Cohort 4. Have you been able to collect any data from that cohort yet? And I'll jump back in the queue.

兩個簡單的問題。第一個問題是，您能否談談您非常創新的主要終點（即共同主要終點）的動力？然後是針對第 4 組的簡短問題。你已經從該群體中收集到任何數據了嗎？我將重新回到隊列中。

Thank you again.

再次感謝您。

I'll hand that over to Alan to answer.

我會把這個問題交給艾倫來回答。

So with regard to powering of the study, it is, I would say, very highly powered to detect statistically significant differences between the treatment arm and the placebo arm, across a range of potential deltas between groups. And I think that atumelnant is well situated to achieve this endpoint that Dana discussed earlier, showing both normalization of A4 and physiologic dosing of glucocorticoid.

因此，就研究的功效而言，我想說，它具有極高的功效，可以在組間一系列潛在差異中，檢測出治療組和安慰劑組之間的統計學顯著差異。我認為 atumelnant 非常適合實現 Dana 之前討論的這個終點，即顯示 A4 的正常化和糖皮質激素的生理劑量。

With regard to Cohort 4, this is enrolling, and I can't speak yet to timing of data. I think what we would do, of course, is show new data at scientific meetings. But the timing of that, I can't comment on quite yet. One other thing I'd like to mention is the kind of primary endpoint we're talking about, I think it's better described as a composite endpoint rather than a co-primary endpoint.

關於第 4 組，這是招募，我還不能說出數據的時間。我認為我們當然會在科學會議上展示新數據。但目前我還不能對具體時間發表評論。我想提及的另一件事是我們正在討論的主要終點類型，我認為最好將其描述為複合終點，而不是共同主要終點。

There are 2 components to the endpoint. A co-primary, though is something else where you kind of have to -- each component has to statistically stand by itself. Whereas a co-primary is -- it's basically a responder analysis where a responder is defined as having both normal glucocorticoid doses and normal A4 levels.

端點有 2 個組件。然而，共同主要性是你必須做到的另一件事——每個組成部分都必須在統計上獨立存在。而共同原發性——它基本上是一種反應者分析，其中反應者被定義為具有正常的糖皮質激素劑量和正常的 A4 水平。

Jessica Fye with JPMorgan.

摩根大通的傑西卡費伊 (Jessica Fye)。

Hey guys, good afternoon. Is the CALM-CAH study design fully signed off on by FDA as a trial that could support registration? And what indication statement would you hope to secure assuming the trial is successful? Do you think you need 1 or 2 trials to get approved for CAH?

大家好，下午好。CALM-CAH 研究設計是否已獲得 FDA 完全批准，可以作為支持註冊的試驗？假設試驗成功，您希望獲得什麼指示聲明？您認為需要 1 或 2 次試驗才能獲得 CAH 批准嗎？

Thank you.

謝謝。

I'll let Dana answer that one.

我請達娜來回答這個問題。

Yes. Sure, Jess. Thanks for the question. The protocol was put together based upon input from FDA as well as other health authorities, and they are aware of the final study design. I think that the other parts of your question.

是的。當然，傑西。謝謝你的提問。該協議是根據 FDA 以及其他衛生當局的意見制定的，他們了解最終的研究設計。我認為您問題的其他部分。

About the indication statement.

關於指示聲明。

Yes. It's hard to say right now on indication. But I think what -- and the data, of course, we will define what we can talk with the agency about. But the basic difference that we have is, what we are trying to develop here is a drug that will treat the disease, the CAH, right. And will only need glucocorticoids for the prevention of adrenal insufficiency, right. So if you look at the chronicity indication, it's as an adjunct to glucocorticoids for the control of androgens. And so that implies that the glucocorticoids are necessary to control the androgens.

是的。目前還很難說具體指徵。但我認為——當然還有數據，我們將定義我們可以與該機構談論的內容。但我們之間的根本區別在於，我們在這裡試圖開發的是一種可以治療 CAH 的藥物。並且只需要使用糖皮質激素來預防腎上腺功能不全，對吧。因此，如果您看一下慢性適應症，它是作為糖皮質激素的輔助手段來控制雄激素。這意味著糖皮質激素對於控制雄性激素是必要的。

In our situation, based upon our Phase II data, it's the atumelnant that's really going to drive the reduction in androgens. And therefore, you don't need glucocorticoids to treat that part of the disease. And as I mentioned when we did the call, we really only expect that the glucocorticoids will be used for physiologic replacement. So we expect that that could result in a slight difference in how the indication is granted.

在我們的情況下，根據我們的第二階段數據，真正推動雄激素減少的是雄激素。因此，您不需要使用糖皮質激素來治療該部分疾病。正如我在通話時提到的那樣，我們實際上只希望使用糖皮質激素進行生理替代。因此，我們預計這可能會導致批准方式略有不同。

Gavin Clark-Gartner with Evercore ISI.

Evercore ISI 的 Gavin Clark-Gartner。

Hey guys, thanks for taking the questions. First, just on the primary endpoint for the Phase III, what's the rationale to test the endpoint at a single point in time at 32 weeks as opposed to averaging across multiple time points? Is there any risk that A4 variability may lead to some non-responders who maybe shouldn't be non-responders?

嘿夥計們，感謝你們回答問題。首先，僅就 III 期臨床試驗的主要終點而言，在 32 週的某個時間點測試終點而不是在多個時間點進行平均的理由是什麼？A4 變異性是否可能導致一些不應該對免疫療法無反應的患者出現免疫療法無反應？

I think generally, responder analyses are conducted at single points in time rather than averages. There is always variability with biochemical markers. Before I think of all the choices in this disease state is one of the least variable. And again, there's a lot of confidence that this compound can achieve both components of the composite primary endpoint.

我認為一般來說，響應者分析是在單一時間點進行的，而不是平均值。生化標記總是存在變化的。在我之前認為這種疾病狀態下的所有選擇是變化最少的一個。再次強調，我們非常有信心這種化合物可以實現複合主要終點的兩個組成部分。

And therefore, the odds that variability would -- variability might explain one of these endpoints hitting it once in a while on an occasional patient, but hitting both is quite, I think, specific. And I would anticipate pretty strong results that are clearly delineated from placebo.

因此，變異性的幾率——變異性可能解釋其中一個終點偶爾發生在某個患者身上，但同時發生在兩個終點上，我認為是相當具體的。我預計會有與安慰劑明顯不同的顯著效果。

Tyler Van Buren with TD Securities.

道明證券的泰勒範布倫 (Tyler Van Buren)。

This is Francis on for Tyler. So just one question about the fourth atumelnant in cohort. So what is the rationale for looking at the morning dosing versus the evening dosing?

這是法蘭西斯代替泰勒上場的。所以我只想問一下關於第四批 atumelnant 的問題。那麼，比較早晨服藥和晚上服藥的理由是什麼呢？

This is Scott. I think for many of us, it'd be more convenient to perhaps take the drug in the morning rather than in the evening. And we just wanted to explore that to provide future optionality for patients. And maybe just to clarify a little bit, reminder that there's a strong diurnal rhythm in this axis, including in CAH patients. And so you just want to be sure that the timing of the drug in respect to the diurnal rhythm doesn't have a significant effect.

這是斯科特。我認為對我們許多人來說，早上服藥可能比晚上服藥更方便。我們只是想探索這一點，為患者提供未來的選擇。也許只是為了稍微澄清一下，提醒一下，這個軸有一個強烈的晝夜節律，包括 CAH 患者。因此，您只需要確保藥物的服用時間不會對晝夜節律產生顯著影響。

Corey Joinville with Lifei Capital.

Corey Joinville 與 Lifei Capital 合作。

So you folks have recently received acceptance for your marketing application for paltusotine in Europe. Curious how you're thinking about launch strategy in these different geographies. You previously discussed patient concentration in the U.S. is largely at these pituitary centers of excellence. Is patient concentration similar to those in Europe and or Latin America? And what, if any, are some of the material differences in the way that acromegaly patients might be treated in those geographies that might be important to consider for a launch?

因此，你們最近已獲得歐洲對 paltusotine 的營銷申請的批准。好奇您是如何考慮在這些不同地區實施發布策略的。您之前討論過，美國的患者主要集中在這些腦下垂體卓越中心。患者集中度是否與歐洲或拉丁美洲相似？那麼，在這些地區，肢端肥大症患者的治療方式是否存在一些實質差異，這些差異對於產品的上市可能具有重要意義？

So yes, I was going to hand that off to Isabel, who is on the line here. Go ahead, Isabel. Sorry.

是的，我打算把這個交給線上的伊莎貝爾。繼續吧，伊莎貝爾。對不起。

Sure. No problem. Yes. So we are very excited to have the filing approved, and we are preparing for the launch in Germany where also there is a significant unmet need for patients with acromegaly. So to your question, the European markets tend to be more concentrated in terms of even more patients are part of the centers of excellence. There is a little bit more of community in Germany than the rest of the market, but still a ratio of about 70% to 30%, 70% on key centers. We continue to do research to confirm that. And so highly concentrated.

當然。沒問題。是的。因此，我們非常高興申請能夠獲得批准，我們正在為在德國推出該產品做準備，因為德國對肢端肥大症患者的需求也存在很大的未滿足需求。所以對於您的問題，歐洲市場往往更加集中，因為更多的患者是卓越中心的一部分。德國的社區比其他市場稍微多一點，但主要中心的比例仍在 70% 到 30% 之間，即 70%。我們將繼續進行研究來證實這一點。而且濃度如此高。

We are working extensively in our market access strategy and in our discussions with GBA and the different markets. And we are going to be very progressive and be very thoughtful about how we continue to expand there. So right now, we have a footprint instill. We have our team in place in Germany, and it's a very small group of resources that we think will help us maximize the opportunity there and help as many patients as possible.

我們正在廣泛制定市場准入策略並與大灣區和不同市場進行討論。我們將非常積極進取，並認真考慮如何繼續在那裡擴張。所以現在，我們已經有一個足跡灌輸了。我們在德國設有團隊，我們認為這個由極少數人組成的團隊能夠幫助我們最大限度地利用那裡的機會，幫助盡可能多的患者。

Regarding Latin America, you have seen also that there is a high unmet need and a lot of patients that have been identified. So the one country that we have considered as a country for expansion is Brazil. As you have seen in our clinical trials, over 30 patients in our acromegaly studies were recruited there. We have very good relationships with the different centers, and it's also concentrated. So we see the opportunity there to also serve the patients beyond in the United States. So it's a commitment for Crinetics to actually serve patients not only in the U.S. but in as many countries as possible, but we will be very gradual about our geographic expansion.

關於拉丁美洲，您也看到那裡存在大量未滿足的需求，並且已經確定了許多患者。因此，我們考慮擴張的國家是巴西。正如您在我們的臨床試驗中看到的，我們在肢端肥大症研究中招募了 30 多名患者。我們與不同的中心保持著非常好的關係，而且也很集中。因此，我們看到了為美國以外的患者提供服務的機會。因此，Crinetics 承諾不僅為美國患者提供服務，而且為盡可能多的國家的患者提供服務，但我們將逐步推進地域擴張。

John Wolleben with Citizens.

約翰·沃勒本 (John Wolleben) 與公民們在一起。

This is Catherine on for John. I had a quick question about the 9682 program and the Phase I/II trial, which are about to, I guess, that you're planning to begin soon. Any details you could share on the trial design and kind of what you want to learn? And also any particular safety issues that you're going to be looking out for in this trial?

我是凱瑟琳，代替約翰。我有一個關於 9682 計劃和 I/II 期試驗的快速問題，我猜您計劃很快就要開始這些計劃了。您能分享任何關於試驗設計的細節以及您想要了解的內容嗎？另外，在這次試驗中您要注意哪些特別的安全問題？

Yes. This is Dana. And we look forward to actually sharing a little bit more about this at the R&D Day that we're going to have in June. And so that will be sort of front and center for those discussions. But our general approach is that it's fairly -- it's going to be a fairly standard dose escalation design protocol for oncology.

是的。這是達娜。我們期待在六月的研發日上分享更多相關資訊。因此這將成為這些討論的核心。但我們的整體方法是相當標準的腫瘤劑量遞增設計方案。

And obviously, when you're treating patients as opposed to healthy volunteers in your Phase I, you have additional safeguards and sort of parameters that you're looking at, particularly around safety. But we'll be very excited to share more details on that later.

顯然，當您在第一階段治療患者而不是健康志願者時，您需要採取額外的保護措施並考慮一些參數，特別是在安全方面。但我們稍後會非常高興分享更多細節。

Alex Thompson with Stifel.

亞歷克斯湯普森 (Alex Thompson) 與 Stifel 合作。

Great, thanks for taking our question. Another on the CAH Phase III. Just wondering if you could talk a little bit about your design here in the context of glucocorticoid reduction and investigator discretion. Are there any overall guidelines for how to do this? Or how confident are you that you're not going to see a significant amount of variability here in the study?

太好了，感謝您回答我們的問題。另一個是關於 CAH 第三階段的。只是想知道您是否可以從糖皮質激素減少和研究者判斷的角度來談談您的設計。對於如何做到這一點，是否有任何整體指導方針？或者您有多大信心認為您不會在研究中看到顯著的差異？

Well, I think part of the sort of overall sort of mindset that we're trying to convey in the trial conduct here was that we wanted it to be as similar as possible to the real world in what investigators would want to do in terms of reducing glucocorticoids. Obviously, patients can come in with quite a lot of differences in what their glucocorticoid levels are and some may have very, very high levels.

嗯，我認為我們在試驗過程中試圖傳達的整體心態的一部分是，我們希望它在減少糖皮質激素方面盡可能地與現實世界中的研究人員想要做的事情相似。顯然，患者的糖皮質激素水平可能存在很大差異，有些患者的糖皮質激素水平可能非常非常高。

And so what we wanted to do was allow enough time in the first part and the second part of the trial so that that can be done judiciously and carefully with the investigator deciding what increments they want to use in decreasing that. We have some general guidance that we put in the protocol about what the limits on those increments should be. But in general, we'd like to leave it up to the PIs to decide what's best for their patients that are in the trial.

因此，我們希望在試驗的第一部分和第二部分留出足夠的時間，以便研究人員可以明智而謹慎地進行研究，並決定他們想要使用什麼增量來減少時間。我們在協議中提出了一些關於這些增量限制的一般指引。但總的來說，我們希望讓 PI 決定什麼對參加試驗的患者最有利。

Maxwell Skor with Morgan Stanley

摩根士丹利的 Maxwell Skor

I was just wondering, I recognize you're not interacting directly with CDER for paltusotine. But I was wondering if you'd comment on the evolving regulatory environment overall and how you're thinking about any potential implications for the rare disease space?

我只是好奇，我知道您沒有直接與 CDER 就 paltusotine 進行互動。但我想知道您是否會對不斷變化的整體監管環境發表評論，以及您如何看待這對罕見疾病領域的任何潛在影響？

Thank you.

謝謝。

Yes. As you know, we're working with the CDER part of FDA. And so far, we really haven't seen much of a difference in terms of how things are progressing and across all of the programs, not just with paltusotine. So right now, it seems like regular order for the way that FDA is working, particularly with programs like ours. And most of our programs are rare disease programs. So we don't really see any differences at this point.

是的。如您所知，我們正在與 FDA 的 CDER 部門合作。到目前為止，我們確實沒有看到事情進展和所有項目（不僅僅是帕妥索汀）有太大差異。因此，目前看來，FDA 的工作方式似乎是正常的，特別是對於像我們這樣的計畫。我們的大多數項目都是罕見疾病項目。因此，我們目前確實沒有看到任何差異。

Joseph Schwartz with Leerink Partners.

Leerink Partners 的 Joseph Schwartz。

This is Will on for Joe. Congrats on the progress this quarter. So one on paltusotine. Now that we're getting closer to the eventual commercial launch, could you provide any preliminary comments on how you might be thinking about pricing? And then with the recent MFN pricing headlines, does this change your thinking around the general strategy at all? And finally, can you just remind us of where the drug is manufactured? Thanks so much.

這是威爾代替喬上場。恭喜本季取得的進展。因此，關於 paltusotine 有一個。現在我們越來越接近最終的商業發布，您能否就定價問題提供一些初步意見？那麼，根據最近的最惠國定價新聞，這是否會改變您對整體策略的看法？最後，可以提醒我們一下這種藥物是在哪裡生產的嗎？非常感謝。

So I'll answer the manufacturing and then leave it to Isabel to not answer your question on pricing directly, but give you some thoughts about how we're thinking.

因此，我將回答製造問題，然後讓伊莎貝爾不直接回答您關於定價的問題，而是告訴您一些我們的想法。

In terms of manufacturing, the final tablets are made here in the U.S. and packaging here in the U.S., although we get precursors and final API from Europe and originally in India. So that answers that part. But maybe, Isabel, can you talk just a little bit about the value we're hoping to deliver?

在製造方面，最終的藥片是在美國製造並在美國包裝，儘管我們從歐洲和印度獲得前體和最終的 API。這回答了那部分內容。但是，伊莎貝爾，您能否稍微談談我們希望實現的價值？

Yes, of course. As I mentioned before, the value proposition of paltusotine is resonating really well with payers, fast and set of action, durable effect, easy to use once daily dosage for patients. And also the fact that they don't have to deal with the breakthrough symptoms and the wastage currently associated with injectables. At this time, we're not commenting on price. Of course, it's something that we're looking at very closely. We're conducting market research, advisory works with payers.

是的當然。正如我之前提到的，帕妥索汀的價值主張與付款人產生了很好的共鳴，其作用快速、持久，患者每天只需服用一次即可。而且他們不必處理目前與注射劑相關的突破性症狀和浪費。目前，我們不對價格發表評論。當然，這是我們正在密切關注的事情。我們正在進行市場研究，並為付款人提供諮詢工作。

And as I mentioned, what is very positive for us is that the value proposition is resonating very well, and we are tracking on that. We don't see at this point -- to answering your second question -- any impact in our strategy based on the recent dynamics. But of course, we are closely monitoring that with our government affairs group as well. And we'll continue to do so considering that about 40% of the population is in Medicare and Medicaid -- 30% Medicare, 10% Medicaid -- and we want to continue to monitor the potential impact in the future. But for now, there are no dynamics.

正如我所提到的，對我們來說非常積極的是價值主張引起了很好的共鳴，我們正在追蹤這一點。回答您的第二個問題，我們目前沒有看到最近的動態對我們的策略產生任何影響。當然，我們也與政府事務小組密切關注此事。考慮到大約 40% 的人口享有醫療保險和醫療補助（30% 享受醫療保險，10% 享受醫療補助），我們將繼續這樣做，並且我們希望繼續監測未來的潛在影響。但目前還沒有任何動態。

Dennis Ding with Jefferies.

傑富瑞 (Jefferies) 的丹尼斯丁 (Dennis Ding)。

This is Anthea on for Dennis. On CAH, the long-term extension, can you give an update on enrollment and follow-up there? And what is the critical mass that you need to give another update to investors?

這是丹尼斯的安西婭。關於 CAH 的長期延期，您能否介紹一下招生和後續工作的最新情況？那麼，您需要向投資者提供另一份更新資訊的臨界質量是多少？

Thank you.

謝謝。

Well, enrollment is proceeding, and we will, of course, once we have a critical mass, we would present at the scientific meeting. I can't really comment on numbers and exact timing at this time. But again, the OLE is another way for us to assess how the compound performs in sort of a more real-world setting, which the doctors have control over the dosing of the compound as well as over the dosing of the glucocorticoids. It's always very valuable data for us, and we look forward to reporting that when we can.

嗯，招生正在進行中，當然，一旦達到臨界人數，我們就會在科學會議上展示。我現在無法對數字和具體時間發表評論。但是，OLE 是我們評估化合物在更現實的環境中表現的另一種方式，醫生可以控制化合物的劑量以及糖皮質激素的劑量。對我們來說，這始終是非常寶貴的數據，我們期待在可能的情況下報告這些數據。

David Lebowitz with Citi.

花旗銀行的 David Lebowitz。

Thank you very much for taking my question. The new primary endpoint seems to be a higher bar. And I am curious, do you reserve the ability to maintain also the same primary endpoint as crinecerfont to potentially use if needed for FDA approval?

非常感謝您回答我的問題。新的主要終點似乎是一個更高的標準。我很好奇，您是否保留了與 crinecerfont 相同的主要終點的能力，以便在 FDA 批准時可能使用？

So I think you're right, it is a higher bar. We're asking the study to see if atumelnant can really be the treatment for CAH. And give patients an option so that they don't have to compromise on either glucocorticoid levels or the adrenal precursors that are being produced. And so it's intentionally a high bar, but I think it's designed specifically for atumelnant because that's the type of study that this drug deserves. And maybe I'll let Dana talk about the endpoint cascade.

所以我認為你是對的，這是一個更高的標準。我們要求進行這項研究，以了解 atumelnant 是否真的可以治療 CAH。並為患者提供一個選擇，這樣他們就不必在糖皮質激素水平或正在產生的腎上腺前體上做出妥協。因此，它故意設定了一個高標準，但我認為它是專門為 atumelnant 設計的，因為這種藥物值得進行這種類型的研究。也許我會讓達娜 (Dana) 談論端點級聯。

Well, yes. And I think just along the lines of what Scott was just saying, the patient population is also different from what Crenessity studied in that we have a broader patient population. And as you recall, in their study, basically what they were looking at was trying to reduce GCs and A4 was sort of a side issue. It had to be roughly where it started, okay, which could have been normal, could have been sort of above normal.

嗯，是的。我認為，正如史考特剛才所說的那樣，患者群體也與 Crenessity 所研究的不同，因為我們的患者群體更廣泛。您還記得，在他們的研究中，他們基本上是在嘗試減少 GC，而 A4 只是一個次要問題。它應該大致位於開始的位置，好吧，這可能是正常的，也可能略高於正常水平。

And so what we like to do is be able to address the full population of patients who have CAH, who may have high A4s and not so high GCs, high GCs and normal A4 and high both, right. And so in order to do that, you really can't have the same endpoint as Crenessity had, okay.

因此，我們希望能夠解決所有 CAH 患者的問題，這些患者可能 A4 水平高而 GC 水平不太高，或者 GC 水平高而 A4 水平正常，或者兩者都高，對吧。因此，為了做到這一點，你真的不能擁有與 Crenessity 相同的終點，好吧。

So now we also have a cascade, as I mentioned in the call, of secondary endpoints. And some of those are looking at certain aspects of how quickly we work and then sort of other combinations of particular sort of endpoints of interest. But we also will look in the same way that they did at somewhat similar endpoint for theirs, too, but that's not what we intend to use for the FDA. And you can't -- if we make the primary endpoint, this broader endpoint, that's what it is required to have to get approved. So we can't change the endpoint.

因此，正如我在電話中提到的那樣，現在我們也擁有了次要端點的級聯。其中一些正在研究我們工作速度的某些方面，然後對特定類型的感興趣的端點進行其他組合。但是，我們也會以與他們相同的方式看待他們的類似終點，但這不是我們打算為 FDA 使用的方法。你不能——如果我們將這個更廣泛的端點作為主要端點，那麼它就必須獲得批准。所以我們無法改變端點。

And I think it's maybe important to remind all of us that we're building a study that measures a variety of different parameters of the impact of atumelnant on the lives of CAH patients. And it's that whole package that will be the basis for guiding physicians about how this might be used, should it be approved. And so we're interested in developing a broad profile, and the primary endpoint is one thing, and I know we'll all focus on that. But also getting to how much do we reduce the A4 levels or 17-OHP, which are a couple of our first secondary endpoints because those lowering is important too, even if you only get to slightly above the upper limit of normal.

我認為也許有必要提醒大家，我們正在進行一項研究，測量 atumelnant 對 CAH 患者生活影響的各種不同參數。一旦獲得批准，這整套方案將成為指導醫生如何使用它的基礎。因此，我們有興趣發展一個廣泛的概況，主要終點是一回事，我知道我們都會關注這一點。但也要考慮我們將 A4 水平或 17-OHP 降低多少，這是我們的幾個首要次要終點，因為降低這些水平也很重要，即使你只達到略高於正常上限的水平。

So the goal of the study is to capture all of this to provide ability to guide physicians and then eventually to use in our commercialization efforts.

因此，研究的目標是捕捉所有這些信息，以提供指導醫生的能力，並最終用於我們的商業化努力。

And we also intend to look closely at the other clinical endpoints and adrenal size as well.

我們還打算密切關注其他臨床終點和腎上腺大小。

Brian Skorney with Baird

布萊恩·斯科尼與貝爾德

Just also on the CAH study. In terms of enrollment criteria, how do you kind of compare exclusion/inclusion criteria to the CATALYST study? Are there differences in criteria and GC dose A4, 17-OHP to consider? And the pediatric plan you have built as a Phase II/III, is this just nomenclature? Or is there a dose-finding portion to the ped study that proceeds full Phase III enrollment?

也涉及 CAH 研究。就入學標準而言，您如何將排除/納入標準與 CATALYST 研究進行比較？標準和 GC 劑量 A4、17-OHP 是否有差異需要考慮？而您所製定的 II/III 期兒科計畫只是一種命名法嗎？或在進行完整 III 期招募的兒科研究中是否有劑量探索部分？

Okay. Just to make sure that I understand, like the -- you asked about the entry criteria for our trial, first for the adult trial. And I think that, as I mentioned before, what we're trying to do is to capture a broader population than the previous trial from crinecerfont. So now in terms of our pediatric program, we've also received feedback from health authorities on that.

好的。只是為了確保我理解，就像——您詢問我們的試驗的入選標準，首先是成人試驗。我認為，正如我之前提到的，我們正在嘗試做的是涵蓋比 crinecerfont 之前的試驗更廣泛的人群。因此，就我們的兒科計畫而言，我們也收到了衛生當局的回饋。

And we're going to try to achieve the same things that we're doing for the adult program, and we just need to make sure that we have the doses right for the right size kids. And so we'll be gradually working through that. But we don't plan to do it differently. And as you will recall in the crinecerfont trial, they didn't -- they held the GCs constant, right, in that one. So there was no GC reduction. So that's sort of one of the big differences.

我們將努力實現與成人計劃相同的目標，我們只需要確保為適當體型的孩子提供合適的劑量。因此我們將逐步解決這個問題。但我們並不打算採取不同的做法。你會記得，在 crinecerfont 審判中，他們沒有 — — 他們在那次審判中保持 GC 不變，對吧。所以 GC 沒有減少。這就是最大的區別之一。

Douglas Tsao with H.C. Wainwright.

Douglas Tsao 與 H.C.溫賴特。

Welcome to Toby to the Crinetics call. [We hope to hear from you, not on a recent ad call]. But maybe just as a follow-up on CAH and the pediatric study. I'm just curious how you think about that program moving forward. Do you anticipate sort of -- Dana, you referred to sort of need to do some dose exploration. Would you anticipate needing potentially to do 2 studies there? Or do you think there's an opportunity to do an adaptive design, which would enable you to only run one study?

歡迎 Toby 參加 Crinetics 電話會議。[我們希望收到您的來信，而不是最近的廣告電話]。但也許只是作為 CAH 和兒科研究的後續研究。我只是好奇您對該計劃的未來發展有何看法。您是否預料到—達娜，您提到需要做一些劑量探索。您是否預計可能需要在那裡進行兩項研究？或者您認為是否有機會進行自適應設計，使您能夠只進行一項研究？

And again, would you anticipate -- you just said that you anticipate sort of having the same goals as with the CALM-CAH study. Does that imply that you would think about the same endpoint in terms of normalization A4 and physiologic GC? Or is there some other potential sort of similar endpoint, but perhaps a slightly different one for targeted for the pediatric population?

再說一次，您是否預期—您剛才說您預期會實現與 CALM-CAH 研究相同的目標。這是否意味著您會從正常化 A4 和生理 GC 的角度考慮相同的終點？或者是否存在其他潛在的類似終點，但針對兒科族群的終點可能略有不同？

Thank you.

謝謝。

Well, I think to answer your first part of your question, and maybe Alan can comment on the sort of treatment objectives. But as far as the first question, the way we've designed this study is to be sort of a seamless design, right, as opposed to 2 separate trials. And so the way that it will work is the Phase II part will guide the Phase III part. And so we don't plan on doing separate trials on that. But I think maybe if Alan can comment on the treatment objectives for the pediatricians on this.

好吧，我想回答你問題的第一部分，也許艾倫可以對治療目標進行評論。但就第一個問題而言，我們設計這項研究的方式是一種無縫設計，對吧，而不是兩個獨立的試驗。因此，其運作方式是第二階段部分將指導第三階段部分。因此我們不打算對此進行單獨試驗。但我想也許艾倫可以就兒科醫生的治療目標發表評論。

Yes. The reason I'm really excited and very supportive of this endpoint that we're talking about, normal GCs and normal A4s, is because this really is the treatment goal for this disease. And by the way, it's same for pediatric patients and adult patients. This is what you want to achieve in clinic. It's very hard to do that these days with available treatments. We really think atumelnant has a lot to offer here to achieve that binary -- 2-part goal. So yes, I think it would be very similar in pediatric patients ultimately.

是的。我之所以對我們正在討論的這個終點（正常的 GC 和正常的 A4）感到非常興奮和支持，是因為這確實是這種疾病的治療目標。順便說一句，兒科患者和成人患者的情況是一樣的。這就是您想在臨床上實現的目標。目前現有的治療方法很難做到這一點。我們確實認為 atumelnant 可以提供很多幫助來實現二元目標。所以是的，我認為最終兒科患者的情況會非常相似。

Andy Chen with Wolfe Research.

沃爾夫研究公司的安迪陳 (Andy Chen)。

Hey, thank you for taking the question. And back to your Phase III trial design. So I understand that the speed of reduction is individualized, but is it mandatory reduction at each stage of GC reduction? Or is it optional reduction for patients? If it's optional, does that make the primary endpoint very wonky and highly dependent on baseline characteristics of patients? Is that a worry here or no?

嘿，謝謝你回答這個問題。回到您的第三階段試驗設計。所以我明白減少的速度是因人而異的，但 GC 減少的每個階段都是強制減少的嗎？或者說，這是病人可選擇的減量嗎？如果它是可選的，那是否會使主要終點變得非常不穩定並且高度依賴於患者的基線特徵？這是否是一個值得擔心的問題？

Thank you.

謝謝。

Well, maybe just -- this is Scott, just as a quick reminder. We may have patients in who have physiologic replacement, but their A4 levels are already high. So they don't need a glucocorticoid reduction. So you have to account for that in the way you design the protocol. But maybe you want to explain a little bit more, Alan.

好吧，也許只是——我是斯科特，只是一個快速提醒。我們可能有患者進行了生理替代，但他們的 A4 水平已經很高了。所以他們不需要減少糖皮質激素。因此，您必須在設計協議時考慮到這一點。但是也許你想進一步解釋一下，艾倫。

Right. That's a good point, Scott. And those who do come in on high glucocorticoid doses, I want to be clear that, yes, this is not optional. The protocol requires, particularly at certain predefined visits, glucocorticoid dose reductions. Of course, the investigator has to make the -- individualize these dose reductions based on toleration and safety. But these dose reductions are expected and would be very carefully monitored and followed. And I agree, it's important to reduce the doses of glucocorticoid in those who come in on high doses in order to achieve this endpoint, and also to achieve the goal in clinic, which is the same. So yes.

正確的。斯科特，你的觀點很好。對於那些確實需要服用高劑量糖皮質激素的人，我想明確指出，這是必須的。該方案要求減少糖皮質激素劑量，特別是在某些預定的訪問中。當然，研究人員必須根據耐受性和安全性來個性化地減少劑量。但這些劑量的減少是預料之中的，並且會受到非常仔細的監測和追蹤。我同意，對於接受高劑量治療的患者，減少糖皮質激素的劑量非常重要，這樣才能達到這個終點，同時也能達到臨床的目標，這是一樣的。是的。

(Operator Instructions)

（操作員指示）

Catherine Novak with Jones.

凱瑟琳·諾瓦克和瓊斯。

Hi, afternoon, everyone. Just wanted to ask one question about paltusotine. So based on PATHFNDR-2, we know you can go into treatment-naive patients, but do you anticipate any possible step-through requirements for payers based on price? How are you thinking about that?

大家下午好。只是想問一個關於 paltusotine 的問題。因此，基於 PATHFNDR-2，我們知道您可以進入未接受治療的患者，但您是否預期付款人可能會根據價格提出任何逐步要求？您對此有何看法？

Isabel?

伊莎貝爾？

Well, as you know, we had PATHFNDR-2 was looking at naive patients, also washout patients and patients that had discontinued and continuing therapy. Our current discussions with payers don't anticipate any step therapy. And so far, the feedback is that they will really just hold us to the label in terms of prior authorization, which in general is a very positive sign for us. And at this point, we don't anticipate the price.

嗯，如您所知，我們的 PATHFNDR-2 正在研究初治患者、洗脫患者以及已停止和繼續治療的患者。我們目前與付款人的討論並不預期任何逐步療法。到目前為止，回饋是他們實際上只會在事先授權方面要求我們遵守標籤，這對我們來說總體上是一個非常積極的信號。目前，我們還沒有預測價格。

We currently have no further questions. I'll now hand back to Scott Struthers for closing remarks.

目前我們沒有其他問題。現在我將把發言交還給斯科特·斯特拉瑟斯，請他作最後發言。

Thank you, everybody, for being with us today. And maybe I'll just take a brief moment to also thank our colleagues at the FDA for their hard work on multiple different programs we're working on and keeping up the normal course of business, at least as far as we've seen. So thank you all, and have a great afternoon and weekend.

謝謝大家今天與我們在一起。也許我只是想花一點時間來感謝 FDA 的同事們，感謝他們在我們正在進行的多個不同項目上所做的努力，並保持著正常的業務進程，至少就我們所見而言。謝謝大家，祝大家下午和週末愉快。

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

今天的電話會議到此結束。感謝您的加入。現在您可以斷開線路了。