Cytokinetics Inc (CYTK) 2024 Q4 法說會逐字稿

Good afternoon, and welcome to Cytokinetics' fourth-quarter 2024 conference call. At this time, I would like to inform you that this call is being recorded. (Operator Instructions)

下午好，歡迎參加 Cytokinetics 2024 年第四季電話會議。此時，我想通知您，本次通話正在錄音。（操作員指示）

I will now turn the call over to Diane Weiser, Cytokinetics' Senior Vice President of Corporate Affairs. Please go ahead.

現在我將電話轉給 Cytokinetics 公司事務資深副總裁 Diane Weiser。請繼續。

Good afternoon, and thanks for joining us on the call today. Robert Blum, President and Chief Executive Officer, will begin with an overview of the quarter and recent developments. Andrew Callos, EVP and Chief Commercial Officer will address commercial readiness activities for aficamten. Fady Malik, EVP of R&D, will provide updates related to clinical development program for aficamten.

下午好，感謝您今天參加我們的電話會議。總裁兼執行長羅伯特布魯姆 (Robert Blum) 將首先概述本季的情況和近期發展情況。執行副總裁兼商務長 Andrew Callos 將負責 aficamten 的商業準備活動。研發執行副總裁 Fady Malik 將提供有關 aficamten 臨床開發計劃的最新資訊。

Isaac Ciechanover, EVP Corporate Development and Chief Business Officer, will provide update on recently announced business development deal in the context of our corporate development. Stuart Kupfer, SVP and Chief Medical Officer, will provide updates regarding omecamtiv mecarbil, CK-586 and our earlier stage development pipeline. Sung Lee, EVP and Chief Financial Officer, will provide a financial overview of the past quarter and discuss our 2025 financial guidance. And finally, Robert will review expected key milestones for year ahead.

企業發展執行副總裁兼商務長 Isaac Ciechanover 將在企業發展背景下介紹最近宣布的業務發展協議的最新情況。高級副總裁兼首席醫療官 Stuart Kupfer 將提供有關 omecamtiv mecarbil、CK-586 和我們早期開發管道的最新資訊。執行副總裁兼財務長 Sung Lee 將提供上個季度的財務概覽並討論我們的 2025 年財務指導。最後，羅伯特將回顧未來一年預期的關鍵里程碑。

Please note that portions of the following discussion, including our responses to questions, contain statements that relate to future events and performance rather than historical facts and constitute forward-looking statements. Our actual results might differ materially from those projected in these forward-looking statements.

請注意，以下討論的部分內容（包括我們對問題的回答）包含與未來事件和表現而非歷史事實相關的陳述，並構成前瞻性陳述。我們的實際結果可能與這些前瞻性陳述中預測的結果有重大差異。

Additional information concerning factors that could cause our actual results to differ materially from those in these forward-looking statements is contained in our SEC filings, including our current report regarding our fourth quarter 2024 financial results filed on Form 8-K that was furnished to the SEC today. We undertake no obligation to update any forward-looking statements after this call. And now I will turn the call over to Robert.

有關可能導致我們的實際結果與這些前瞻性陳述中的結果存在重大差異的因素的其他資訊包含在我們向美國證券交易委員會提交的文件中，包括我們今天向美國證券交易委員會提交的 8-K 表格中關於我們 2024 年第四季度財務業績的最新報告。我們不承擔本次電話會議後更新任何前瞻性聲明的義務。現在我將把電話轉給羅伯特。

Thank you, Diane and thanks to all for joining us on the call today. The fourth quarter of 2024 was an exceptionally productive quarter that rounded out a successful year. Most notably, we made major strides towards potential regulatory approvals and subsequent commercial launches of aficamten across multiple geographies. Our NDA was accepted by FDA. Our MAA was validated by EMA and our NDA was accepted by the NMPA in China with priority review.

謝謝你，黛安，也謝謝大家今天參加我們的電話會議。2024 年第四季是一個異常高產的季度，為成功的一年畫上了圓滿的句號。最值得注意的是，我們在獲得潛在監管部門批准以及隨後在多個地區推出 aficamten 的商業化方面取得了重大進展。我們的 NDA 已被 FDA 接受。我們的 MAA 已獲得 EMA 的驗證，我們的 NDA 已被中國 NMPA 接受並獲得優先審查。

Now with regulatory submissions on file in the US, Europe and China, we're engaging in parallel regulatory interactions that may deliver aficamten to patients around the world. With our PDUFA date of September 26, 2025, our commercial readiness activities in the United States are reaching a peak, while we also lay the foundation for our go-to-market activities in Europe. In the near term, we expect to continue already ongoing activities with FDA in support of their review of the NDA. We have been responding to questions as well as preparing for clinical site and other inspections and we recently submitted our 120-day safety update to FDA.

目前，我們已向美國、歐洲和中國提交了監管申請，正在進行平行的監管互動，以便為世界各地的患者提供阿菲卡姆汀。隨著我們的 PDUFA 日期為 2025 年 9 月 26 日，我們在美國的商業準備活動正在達到頂峰，同時我們也為我們在歐洲的上市活動奠定了基礎。在短期內，我們期望繼續與 FDA 進行正在進行的活動，以支持他們對 NDA 的審查。我們一直在回答問題並為臨床現場和其他檢查做準備，最近我們向 FDA 提交了 120 天安全更新。

In March, we expect to participate in a mid-cycle meeting with FDA. Ahead of that meeting, I want to level set that we do not plan to share detailed updates following that meeting given that the FDA review of the NDA will still be ongoing. However, we maintain our expectation for a differentiated label and [Indiscernible] profile for aficamten were it to be approved by FDA.

三月份，我們預計將參加與 FDA 的中期會議。在那次會議之前，我想明確表示，由於 FDA 對 NDA 的審查仍在進行中，我們不打算在那次會議之後分享詳細的更新資訊。然而，如果 aficamten 獲得 FDA 批准，我們仍然期望它具有差異化的標籤和 [音訊不清晰] 特性。

In both SEQUOIA-HCM and FOREST-HCM, in patients with oHCM, we observed a favorable overall safety profile, LVEF stability, rapid dose titration, as well as a lack of treatment interruptions related to episodes of heart failure or heart failure of heart failure or heart failure hospitalizations related to LVEF nor did we observe any clinically meaningful drug-drug interactions. We believe all of these characteristics are consistent with the intrinsic properties of aficamten.

在 SEQUOIA-HCM 和 FOREST-HCM 中，對於 oHCM 患者，我們觀察到良好的整體安全性、LVEF 穩定性、快速劑量滴定，以及缺乏與心臟衰竭發作或心臟衰竭或與 LVEF 相關的心臟衰竭住院相關的治療中斷，也沒有觀察到任何具有臨床意義的藥物交互作用。我們相信所有這些特徵都與 aficamten 的固有屬性一致。

Moving on to the regulatory review of aficamten in Europe, following the validation of our MAA in late December, we expect to continue to engage with EMA during their review by responding to request for information and preparing for inspections. Our next key milestone for these regulatory interactions with EMA is receipt of the day 120 list of questions expected in April. As you know, we plan to commercialize aficamten in ourselves in the US and Western Europe.

繼續進行歐洲對 aficamten 的監管審查，在 12 月下旬我們的 MAA 獲得驗證之後，我們希望在 EMA 審查期間繼續與其合作，回應資訊請求並準備接受檢查。我們與 EMA 監管互動的下一個重要里程碑是收到預計在 4 月發出的第 120 天的問題清單。如您所知，我們計劃在美國和西歐自行實現 aficamten 的商業化。

In other key geographies in the fourth quarter, Sanofi acquired with our participation from CORXEL the rights to develop and commercialize aficamten in China. Additionally, in November, we announced our new collaboration with Bayer that entails a license agreement for aficamten in Japan. These two strong pharmaceutical company partners in the two leading markets outside The US and Europe both align with Cytokinetics in their commitment to cardiology and each brings great expertise, resources and reach to enable us to hopefully deliver aficamten to a greater number of HCM patients in need and contribute to our goal to reach patients globally with our medicines.

在第四季度的其他主要地區，賽諾菲透過我們的參與從CORXEL手中獲得了在中國開發和商業化aficamten的權利。此外，11 月，我們宣布與拜耳達成新的合作，其中包括在日本簽署 aficamten 的授權協議。這兩家實力雄厚的製藥公司在美國和歐洲以外的兩個主要市場均與 Cytokinetics 合作，致力於心臟病學研究，並各自帶來豐富的專業知識、資源和影響力，使我們能夠為更多有需要的 HCM 患者提供阿菲卡姆汀，並幫助我們實現讓全球患者享受到我們藥物的目標。

Simultaneously, we're advancing our later stage development program for aficamten with multiple ongoing potential label expansion clinical trials. In the near term, we expect to share top line results from MAPLE-HCM in Q2 and if positive data from this trial may represent again a label expansion opportunity for aficamten following potential FDA approval. Meanwhile, we continue to expand our specialty cardiology franchise and innovative pipeline advancements ensuring that we're more than simply a one product company.

同時，我們正在推動 aficamten 的後期開發計劃，並正在進行多項潛在標籤擴展臨床試驗。短期內，我們預計將在第二季度分享 MAPLE-HCM 的頂線結果，如果此次試驗的積極數據可能再次代表 aficamten 在獲得 FDA 批准後有標籤擴展的機會。同時，我們繼續擴大我們的專業心臟病學特許經營權和創新管道進步，確保我們不僅僅是一家單一產品的公司。

In Q4, we started COMET-HF, a confirmatory Phase three clinical trial of omecamtiv in patients with heart failure with severely reduced ejection fraction. And more recently we started AMBER- HFpEF, a Phase 2 clinical trial of CK-586 in patients with heart failure and preserved ejection fraction.

在第四季度，我們啟動了 COMET-HF，這是一項針對射血分數嚴重降低的心臟衰竭患者的 omecamtiv 驗證性三期臨床試驗。最近，我們啟動了 AMBER-HFpEF，這是針對心臟衰竭和射血分數保留的患者進行的 CK-586 第 2 期臨床試驗。

Our successes over the past quarter reflect our clear vision, strategic execution and responsible investment in our muscle biology platform. This year, we're approaching a defining moment with key milestones ahead that will shape our future as multiple programs advance in our specialty cardiology franchise alongside progress in our early-stage neuromuscular pipeline as well as continued innovation in our research labs, we're poised to drive meaningful progress to positively impact the lives of patients as well as create enduring value for shareholders who support our mission.

我們過去一個季度的成功反映了我們對肌肉生物學平台的清晰願景、策略執行和負責任的投資。今年，我們即將迎來一個決定性的時刻，隨著我們專業心臟病學特許經營中的多個項目取得進展、早期神經肌肉管道取得進展以及研究實驗室持續創新，我們將迎來塑造未來的關鍵里程碑，我們準備推動有意義的進展，對患者的生活產生積極影響，並為支持我們使命的股東創造持久的價值。

With that, I'll now turn the call over to Andrew.

說完這些，我現在將電話轉給安德魯。

Thanks, Robert. Our launch preparations for aficamten are well underway with significant momentum in 2024 and setting up what is the final stretch towards a potential US approval and launch of our first medicine in September. The priorities we are guiding towards for a successful launch are as follows: broadening category awareness and effectively communicating the differentiated attributes of aficamten, galvanizing and activating new cardiologist prescriptions, securing access and an affordable copay for people with HCM and providing exceptional patient support. Of note, we are pleased to see continued category expansion of the number of patients treated with a cardiac myosin inhibitor or CMI.

謝謝，羅伯特。我們對 aficamten 的上市準備工作正在順利進行中，2024 年的勢頭十分強勁，為 9 月份獲得美國批准和推出我們的第一種藥物做好了最後衝刺。為了成功推出該產品，我們採取的優先措施如下：擴大類別意識並有效傳達阿菲卡姆滕的差異化屬性、激發和激活新的心臟病專家處方、確保 HCM 患者能夠獲得藥物並獲得可負擔的自付費用，並提供卓越的患者支持。值得注意的是，我們很高興看到接受心肌肌球蛋白抑制劑或 CMI 治療的患者數量不斷擴大。

Continued market growth and broad awareness is good news for Cytokinetics as it reflects a growing opportunity for aficamten to capture what is largely still an untapped market. Cytokinetics will be focused on increasing market awareness and category penetration and broader cardiology adoption for CMIs with aficamten. Toward that objective in the fourth quarter, we are proud to drive increased education and awareness of HCM with the launch of HCM Beyond The Heart, an unbranded disease awareness campaign featuring real people with HCM. In October, we launched the campaign directed to HCPs to inspire them to look deeper for HCM and practice whole person care.

持續的市場成長和廣泛的知名度對 Cytokinetics 來說是個好消息，因為這反映出 aficamten 有越來越多的機會佔領尚未開發的市場。Cytokinetics 將致力於提高市場知名度和類別滲透率，並擴大含有阿菲卡汀的 CMI 在心臟病學中的應用。為了實現第四季度的這一目標，我們很榮幸能夠透過推出「HCM Beyond The Heart」來推動對 HCM 的教育和認識，這是一項非品牌疾病宣傳活動，以真實的 HCM 患者為對象。十月份，我們發起了針對 HCP 的活動，以激勵他們更深入地了解 HCM 並實踐全人護理。

Initial engagement metrics with the website and emails are above industry benchmark for our target audience. In January, we expanded HCM Beyond the Heart inclusive of patients, incorporating a website, educational tools and resources focused not just on the condition, but in the impact it has on a patient's lives beyond their heart. This represents another exciting milestone as we move forward toward the PDUFA date later this year. Meanwhile, we continue developing, refining our branded HCP promotional campaign for aficamten, which is currently being tested with HCPs.

對於我們的目標受眾來說，網站和電子郵件的初始參與度指標高於行業基準。今年 1 月，我們將 HCM 擴展到心臟以外的領域，納入患者，建立了網站、提供教育工具和資源，不僅關注病情，還關注其對患者心臟以外生活的影響。這是我們在今年稍後向 PDUFA 日期邁進的又一個令人興奮的里程碑。同時，我們持續開發並完善針對 aficamten 的品牌 HCP 促銷活動，目前正在與 HCP 進行測試。

To support our goal of ensuring product and market access post approval, we have continued our engagement with payers while advancing implementation of a robust patient support program. This includes contracting with strategic partners, determining the size and approach of our customer facing Nurse Navigator team and creating a bespoke patient experience offering. We also advanced operational planning for our sales force, including finalizing the sales training curriculum and sales territory configurations and deployment, and we finalized our sales representative recruiting process, which will be initiated in late Q1.

為了支持我們確保產品和市場准入後獲得批准的目標，我們繼續與付款人合作，同時推動實施強有力的患者支持計劃。這包括與策略合作夥伴簽訂合同，確定面向客戶的護理人員導航團隊的規模和方法，以及創建客製化的患者體驗服務。我們還為銷售團隊制定了先進的營運規劃，包括確定銷售培訓課程和銷售區域配置和部署，並完成了銷售代表招募流程，該流程將於第一季末啟動。

Beyond the US launch, we're also scaling up commercial launch related activities in international infrastructure to support a potential European approval of aficamten. At the end of last year, we hired key leadership positions in Europe, inclusive of leaders in marketing, finance, human resources and in country leadership in both France and the UK, following our previous hiring of a leader in Germany earlier in the prior year.

除了在美國推出之外，我們還在擴大國際基礎設施的商業發布相關活動，以支持歐洲可能批准阿菲卡姆汀。繼去年年初我們在德國聘請了一位領導人之後，去年年底，我們在歐洲聘用了關鍵領導職位，包括行銷、財務、人力資源以及法國和英國的國家領導。

Recent planning activities are ahead of a potential European approval, including validation of our reimbursement strategy and initial preparation of dossiers for HTA submission across the UK and Western EU markets. I'm pleased with the progress we've made to prepare for both the US and European commercial launches of aficamten and where we are positioned today on our commercial readiness roadmap.

最近的規劃活動是為了獲得歐洲的批准，包括驗證我們的報銷策略以及初步準備向英國和西歐市場提交 HTA 的文件。我對我們為在美國和歐洲商業發布 aficamten 所取得的進展以及我們目前在商業準備路線圖上所處的位置感到滿意。

With that, I'll turn the call over to Fady.

說完這些，我將把電話轉給 Fady。

Thanks, Andrew. As Robert mentioned, we recently submitted the 120-day safety update to FDA with an additional ten months of safety data from FOREST-HCM. These longer-term data are consistent with the previously presented data from FOREST-HCM and the safety profile of aficamten as reflected in the NDA submission with, we believe, no evidence of an increased risk of EF excursions or heart failure events. As FDA reviews the NDA, we're continuing to answer their questions and prepare for clinical site and other inspections. As Robert mentioned, we also expect to participate in a mid-cycle meeting with FDA in March.

謝謝，安德魯。正如羅伯特所提到的，我們最近向 FDA 提交了 120 天的安全更新，其中還包含來自 FOREST-HCM 的另外 10 個月的安全數據。這些長期數據與先前提供的 FOREST-HCM 數據以及 NDA 提交中反映的阿菲卡姆滕的安全性概況一致，我們認為沒有證據表明 EF 偏差或心臟衰竭事件的風險增加。在 FDA 審查 NDA 時，我們將繼續回答他們的問題並為臨床現場和其他檢查做準備。正如羅伯特所提到的，我們也預計將於 3 月參加與 FDA 的中期會議。

Moving on to our work in the fourth quarter to expand the evidence base for aficamten. At the American Heart Association Scientific Sessions in November, we presented data from two prespecified analyses of SEQUOIA-HCM and one analysis of FOREST-HCM. Expanding on our activities to make data from this program available to the medical community. These presentations included analyses of post exercise oxygen uptake recovery, patient quality of life and guideline eligibility for septal reduction therapy, all favorably impacted by aficamten.

我們將在第四季繼續開展工作，擴大 aficamten 的證據基礎。在 11 月的美國心臟協會科學會議上，我們展示了兩項預先指定的 SEQUOIA-HCM 分析和一項 FOREST-HCM 分析的數據。擴大我們的活動，使該計劃的數據可供醫學界使用。這些報告包括對運動後氧攝取量恢復、患者生活品質和間隔縮小治療指南資格的分析，所有這些都受到了阿菲卡姆滕的積極影響。

In addition to disseminating data during the quarter, our managed healthcare MSL team continued preapproval information exchange to actively engage national and regional payers in scientific discussions related to oHCM and aficamten and notified payers of our PDUFA date. Scientific engagement with HCM specialists also continued with discussions focused on the results from SEQUOIA-HCM, including the primary results and secondary data analyses.

除了在本季度傳播數據外，我們的管理醫療 MSL 團隊還繼續進行預先批准資訊交換，積極讓國家和地區付款人參與與 oHCM 和 aficamten 相關的科學討論，並通知付款人我們的 PDUFA 日期。與 HCM 專家的科學交流也持續進行，討論重點是 SEQUOIA-HCM 的結果，包括主要結果和二次資料分析。

Now shifting to the ongoing clinical trials program for aficamten, having completed enrollment in MAPLE-HCM in the third quarter of last year, we continue to conduct the trial, collect data and progress towards database lock. We're on track to share top line results in the second quarter of this year, which we expect to be followed by a presentation of the full results at a subsequent medical meeting. If the results of MAPLE-HCM are positive, it'll provide an opportunity to elevate aficamten as a potential monotherapy for the treatment of oHCM following approval.

現在轉向正在進行的 aficamten 臨床試驗計劃，我們已於去年第三季度完成 MAPLE-HCM 的註冊，我們將繼續進行試驗、收集數據並推進資料庫鎖定。我們預計在今年第二季分享最重要的結果，並預計隨後的醫學會議上展示完整的結果。如果 MAPLE-HCM 的結果是正面的，那麼它將為阿菲卡汀在獲批後作為治療 oHCM 的潛在單一療法提供機會。

Meanwhile, we've continued to conduct ACACIA-HCM pivotal Phase three clinical trial in non-obstructive HCM, CEDAR-HCM in pediatric population of patients with symptomatic oHCM, and of course, FOREST-HCM, the ongoing open label extension clinical study.

同時，我們繼續在非阻塞性HCM中進行ACACIA-HCM關鍵性第三期臨床試驗，在有症狀的兒科oHCM患者中進行CEDAR-HCM，當然還有正在進行的開放標籤擴展臨床研究FOREST-HCM。

FOREST-HCM continues to grow with now over 400 patients enrolled, nearly 300 patients have at least a year of follow-up and over 90 have two years of follow-up. We're pleased to report that patient enrollment in ACACIA-HCM has progressed rapidly over the last few months, thanks to our highly engaged sites. We've completed site activations in North and South America, Europe and Israel and are pleased with the baseline characteristic of the population. Results from this trial represent a key future milestone for the potential label expansion trajectory for aficamten into non-obstructive HCM.

FOREST-HCM 持續發展，目前已招募超過 400 名患者，近 300 名患者至少接受一年的隨訪，超過 90 名患者接受兩年的隨訪。我們很高興地報告，由於我們高度參與的站點，ACACIA-HCM 的患者招募在過去幾個月中進展迅速。我們已經完成了北美、南美、歐洲和以色列的站點激活，並對人口的基線特徵感到滿意。該試驗的結果代表了阿法卡坦在非阻塞性 HCM 中的潛在標籤擴展軌跡未來的一個重要里程碑。

While today representing about 1/3 of the HCM population, nHCM appears to be growing at a faster rate than oHCM in terms of diagnoses, such that we expect it to eventually represent nearly half of HCM diagnoses. So it's an important segment of the population that needs to be addressed, in particular because nHCM lacks effective medical or surgical therapy unlike oHCM.

儘管目前 nHCM 約佔 HCM 人口的 1/3，但就診斷而言，nHCM 的成長速度似乎比 oHCM 更快，因此我們預計它最終將佔 HCM 診斷的近一半。因此，這是需要解決的重要族群群體，特別是因為與 oHCM 不同，nHCM 缺乏有效的藥物或手術治療。

Overall from a clinical development perspective, our work in the fourth quarter wrapped up a truly monumental year, highlighted by numerous data presentations and publications in high impact journals. We look forward to building on and publishing that growing clinical evidence in support of aficamten as we approach the potential approval and the launch of aficamten in oHCM this year.

總體而言，從臨床開發的角度來看，我們在第四季度的工作為真正具有里程碑意義的一年畫上了圓滿的句號，其中最引人注目的是大量數據演示和在高影響力期刊上發表的出版物。隨著我們今年接近 aficamten 在 oHCM 的潛在批准和上市，我們期待在此基礎上建立並發布支持 aficamten 的越來越多的臨床證據。

Now I'll turn it over to Isaac.

現在我將把話題交給艾薩克。

Thanks, Fady. As Robert mentioned, we secured two new partnerships in the fourth quarter, which together will support the development and commercialization of aficamten in critical global geographies. We were pleased to enter into a collaboration and licensing agreement with Bayer for the development and commercialization of aficamten in Japan. This deal stands alone in terms of its favorable economics for a cardiovascular drug. EUR50 million in upfront payments to Cytokinetics, eligibility to receive an additional EUR90 million tied to milestones through the commercial launch, EUR490 million in commercial milestone payments from Bayer upon their achievement of certain sale milestones and tiered royalties on net sales of aficamten in Japan.

謝謝，法迪。正如羅伯特所提到的，我們在第四季度獲得了兩個新的合作夥伴關係，它們將共同支持阿菲卡姆汀在全球關鍵地區的開發和商業化。我們很高興與拜耳達成合作和許可協議，以在日本開發和商業化阿菲卡姆汀。就心血管藥物的有利經濟效益而言，這筆交易是獨一無二的。向 Cytokinetics 支付 5000 萬歐元預付款，有資格透過商業發布獲得與里程碑相關的額外 9000 萬歐元，在拜耳實現某些銷售里程碑後向其支付 4.9 億歐元商業里程碑付款，以及根據日本 aficamten 的淨銷售額分級支付特許權使用費。

To support the potential marketing authorization of aficamten in Japan, Bayer will conduct a Phase 3 clinical trial in Japanese patients with oHCM to support SEQUOIA-HCM and FOREST-HCM, while Cytokinetics plans to expand both ACACIA-HCM and CEDAR-HCM into Japan.

為了支持 aficamten 在日本的潛在行銷授權，拜耳將在日本 oHCM 患者中進行 3 期臨床試驗，以支持 SEQUOIA-HCM 和 FOREST-HCM，而 Cytokinetics 計劃將 ACACIA-HCM 和 CEDAR-HCM 都擴展到日本。

As you know, we have been pursuing a deal like this in Japan for some time. Bayer, like Cytokinetics, has a deep commitment to cardiology and through this process ultimately rose to the top of the right partner who is well equipped to bring aficamten to patients in Japan.

如您所知，我們在日本已經尋求達成這樣的交易一段時間了。拜耳與 Cytokinetics 一樣，對心臟病學有著深厚的承諾，並透過這個過程最終成為合適的合作夥伴，有能力為日本患者提供 aficamten。

Additionally, during the fourth quarter, Sanofi acquired exclusive rights to develop and commercialize the aficamten from CORXEL, formerly Ji Xing in China. Through this transaction, Cytokinetics remains eligible to receive up to $150 million in development and commercial milestone payments from Sanofi and royalties in the low to high teens on sales of aficamten in China. Cytokinetics is now also eligible to receive additional payments in connection with the execution of the agreement between Sanofi and CORXEL.

此外，賽諾菲在第四季度從 CORXEL（前身為吉星）獲得了在中國開發和商業化阿法卡因的獨家權利。透過此交易，Cytokinetics 仍有資格從賽諾菲獲得高達 1.5 億美元的開發和商業里程碑付款，以及阿菲卡汀在中國銷售的十幾億美元的特許權使用費。Cytokinetics 現在還可以獲得與賽諾菲和 CORXEL 之間的協議執行相關的額外付款。

Over the years, we have enjoyed a highly productive collaboration with CORXEL and now we are pleased to partner with Sanofi, harnessing their expertise in cardiology to bring aficamten to patients in China. Both of these recent deals serve to expand the potential reach of aficamten in key geographies worldwide.

多年來，我們與 CORXEL 保持著高效的合作，現在我們很高興與賽諾菲合作，利用他們在心臟病學方面的專業知識將阿菲卡姆汀帶給中國患者。這兩筆最新交易都有助於擴大 aficamten 在全球主要地區的潛在影響力。

Now with partners on board in China and Japan and our own commercial infrastructure scaling in the US and Europe, we're turning our attention to how we may further expand our geographic reach with aficamten and how we may also catalyze external R&D activities and pursue new business objectives to augment our existing pipeline alongside innovation from our own labs. To that end, our goal is to bring additional new chemical entities into clinical development through external innovation, seeking complementary potential therapies to support our late-stage cardiovascular franchise and emerging neuromuscular pipeline.

現在，我們在中國和日本擁有合作夥伴，並且我們自己的商業基礎設施在美國和歐洲不斷擴大，我們將注意力轉向如何透過 aficamten 進一步擴大我們的地理覆蓋範圍，以及如何催化外部研發活動並追求新的業務目標，以在我們自己的實驗室進行創新的同時擴大我們現有的產品線。為此，我們的目標是透過外部創新將更多新的化學實體引入臨床開發，尋求補充的潛在療法來支持我們後期的心血管特許經營和新興的神經肌肉管線。

As stated in our Vision 2030, we also seek to expand into new modalities through a combination of both building internal capabilities and identifying external collaborations with industry partners and academic institutions. In the year to come, you can expect more activity on the business and corporate development fronts at Cytokinetics as it relates to bringing aficamten to more patients worldwide, as well as how we may augment our R&D pipeline in more ways that read on progress towards our stated vision. I look forward to sharing more of these matters as they progress.

正如我們的「2030願景」中所述，我們還尋求透過建立內部能力和與產業合作夥伴和學術機構建立外部合作來擴展到新的模式。在未來的一年裡，您可以期待 Cytokinetics 在業務和企業發展方面開展更多活動，因為這涉及到將阿菲卡姆汀帶給全球更多患者，以及我們如何以更多方式擴充我們的研發管道，以推進我們既定願景的進展。我期待著隨著這些事項的進展分享更多相關資訊。

Now I'll hand it over to Stuart.

現在我將把它交給史都華。

Thanks, Isaac. I'm pleased to provide updates on the later stage development programs within our specialty cardiology franchise as well as our earlier stage neuromuscular clinical research. I will start with omecamtiv mecarbil a cardiac myosin activator. During the quarter, we started COMET-HF a confirmatory Phase 3 clinical trail in patients with symptomatic heart failure with severely reduced ejection fraction less than 30%. Since starting the trial, we've seen a great deal of enthusiasm from our investigators who recognize the considerable unmet need in this high-risk population and are eager to enroll patients.

謝謝，艾薩克。我很高興提供有關我們專業心臟病學特許經營中的後期開發計劃以及早期神經肌肉臨床研究的最新資訊。我將從心臟肌球蛋白激活劑 omecamtiv mecarbil 開始。本季度，我們啟動了 COMET-HF 驗證性 3 期臨床試驗，針對射血分數嚴重降低至低於 30% 的症狀性心臟衰竭患者。自試驗開始以來，我們看到研究人員表現出極大的熱情，他們認識到這一高風險族群中存在大量未滿足的需求，並渴望招募患者。

Currently, this trial is enrolling in the United States and regulatory submissions have been completed in Canada, the UK and the rest of Europe. Investigators with prior experience with omecamtiv mecarbil have been reaching out to us regularly to inquire about participating in COMET-HF, and our steering committee is now fully seated with the foremost heart failure leaders from countries where the trial will be conducted.

目前，該試驗正在美國進行招募，並已在加拿大、英國和歐洲其他地區完成監管提交。具有 omecamtiv mecarbil 使用經驗的研究人員一直定期與我們聯繫，詢問參與 COMET-HF 的情況，我們的指導委員會現已完全由來自將進行試驗的國家的最重要的心臟衰竭領導人組成。

Now I'll move on to CK-586, our next cardiac myosin inhibitor. In January of this year, we began AMBER-HFpEF, a Phase 2 placebo controlled double-blind trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamic profile of CK-586 in patients with symptomatic heart failure with preserved ejection fraction and LVEF greater than or equal to sixty percent.

現在我將討論我們的下一個心臟肌球蛋白抑制劑 CK-586。今年 1 月，我們啟動了 AMBER-HFpEF，這是一項 2 期安慰劑對照雙盲試驗，旨在評估 CK-586 對射血分數保留且 LVEF 大於或等於 60% 的症狀性心臟衰竭患者的安全性、耐受性、藥物動力學和藥效學特徵。

AMBER-HFpEF is expected to enroll approximately 60 patients in three 12-week dose escalation cohorts with doses ranging from 160 mg to 600 mg once daily. Potential treatment benefits of CK-586 include increased cardiac relaxation leading to improved diastolic function, improvement of heart failure symptoms and increased exercise capacity, and we expect to build a body of evidence in support of these outcomes through this trial. Our goal is to complete enrollment of the first two cohorts in the second half of the year.

AMBER-HFpEF 預計將招募約 60 名患者，分為三個為期 12 週的劑量遞增組，劑量範圍為每日一次 160 毫克至 600 毫克。CK-586 的潛在治療益處包括增加心臟放鬆從而改善舒張功能、改善心臟衰竭症狀和提高運動能力，我們希望透過這次試驗建立支持這些結果的證據。我們的目標是在今年下半年完成前兩批學生的招生。

Finally, beyond our specialty cardiology franchise, during the fourth quarter, we were pleased to begin a Phase one study of CK-089, a fast skeletal muscle troponin activator. The study comprises both single and multiple ascending dose cohorts. CK-089 arose from our pioneering research in neuromuscular disease and was optimized by our prior learnings. CK-089 is designed to amplify skeletal muscle response to nerve input, extending time to fatigue and increase in muscle force and power with potential therapeutic application to a specific type of muscular dystrophy. We expect to complete this Phase 1 study within 2025 and look forward to keeping you updated on our progress in this key area of clinical research as it underscores a second vertical for our company.

最後，除了我們的專業心臟病學特許經營權之外，在第四季度，我們很高興開始對快速骨骼肌肌鈣蛋白激活劑 CK-089 進行第一階段研究。研究包括單劑量和多劑量遞增組。CK-089 源自於我們在神經肌肉疾病方面的開創性研究，並根據我們先前的研究進行了優化。CK-089 旨在增強骨骼肌對神經輸入的反應，延長疲勞時間並增加肌肉力量和功率，對特定類型的肌肉營養不良症有潛在的治療作用。我們預計將在 2025 年內完成第一階段研究，並期待向您通報我們在這一關鍵臨床研究領域的進展，因為它凸顯了我們公司的第二個垂直領域。

With that, I'll pass it to Sung.

說完這些，我就把它傳給宋了。

Thanks, Stuart. We're pleased to report our fourth quarter and full year 2024 financial results. Starting with the balance sheet, we finished the fourth quarter of 2024 with approximately $1.2 billion in cash, cash equivalents and investments compared to $1.3 billion at the end of the third quarter of 2024.

謝謝，斯圖爾特。我們很高興地報告 2024 年第四季和全年財務表現。從資產負債表開始，到 2024 年第四季末，我們的現金、現金等價物和投資約為 12 億美元，而 2024 年第三季末為 13 億美元。

Cash, cash equivalents and investments declined by approximately $60 million during the fourth quarter of 2024 and benefited from the receipt of $52.4 million or €50 million payment from Bayer for the exclusive license to develop and commercialize aficamten in Japan.

2024 年第四季度，現金、現金等價物和投資減少了約 6,000 萬美元，這得益於拜耳支付了 5,240 萬美元或 5,000 萬歐元，用於獲得在日本開發和商業化 aficamten 的獨家許可。

Moving on to the income statement, the revenues in the fourth quarter of 2024 were $16.9 million compared to $1.7 million for the same period in 2023. The revenues for the full year of 2024 were $18.5 million compared to $7.5 million in 2023. Total revenues in the fourth quarter of 2024 and full year 2024 benefited from a $15 million upfront payment from CORXEL in connection with the assignment of CORXEL’s rights for the development and commercialization of aficamten in Greater China to Sanofi.

再來看損益表，2024 年第四季的營收為 1,690 萬美元，而 2023 年同期的營收為 170 萬美元。2024 年全年營收為 1,850 萬美元，而 2023 年為 750 萬美元。2024 年第四季和 2024 年全年的總收入受益於 CORXEL 支付的 1500 萬美元預付款，該款項與 CORXEL 將其在大中華區開發和商業化阿法卡因的權利轉讓給賽諾菲有關。

R&D expenses for the fourth quarter were $93.6 million compared to $85 million for the same period in 2023. R&D expenses for the full year of 2024 were $339.4 million compared to $330.1 million in 2023. The increase year-over-year for both the fourth quarter and full year was primarily due to advancing our clinical trials and higher personnel related costs including stock-based compensation.

第四季研發費用為 9,360 萬美元，而 2023 年同期為 8,500 萬美元。2024 年全年研發費用為 3.394 億美元，而 2023 年為 3.301 億美元。第四季度和全年同比增長主要歸因於臨床試驗的推進以及包括股票薪酬在內的人員相關成本的增加。

G&A expenses for the fourth quarter of 2024 were $62.3 million compared to $44.1 million for the same period in 2023. G&A expenses for the full year of 2024 were $215.3 million compared to $173.6 million in 2023. The increase year-over-year for both the fourth quarter and full year was primarily driven by investments toward commercial readiness and higher personnel related costs including stock-based compensation.

2024 年第四季的一般及行政費用為 6,230 萬美元，而 2023 年同期為 4,410 萬美元。2024 年全年的 G&A 費用為 2.153 億美元，而 2023 年為 1.736 億美元。第四季和全年的同比增長主要得益於商業準備方面的投資以及包括股票薪酬在內的人員相關成本的增加。

Net loss for the fourth quarter of 2024 was $150 million or $1.26 per share compared to a net loss of $136.9 million or $1.38 per share for the same period in 2023. Net loss for the full year of 2024 was $589.5 million or $5.26 per share compared to a net loss of $526.2 million or $5.45 per share in 2023.

2024 年第四季淨虧損為 1.5 億美元，即每股 1.26 美元，而 2023 年同期淨虧損為 1.369 億美元，即每股 1.38 美元。2024 年全年淨虧損為 5.895 億美元，即每股 5.26 美元，而 2023 年淨虧損為 5.262 億美元，即每股 5.45 美元。

Turning now to our financial guidance for 2025, we expect our GAAP operating expense which is comprised of R&D and SG&A expenses to be between $670 million and $710 million. Stock based compensation included in the GAAP operating expense is expected to be between $110 million and $120 million. Excluding stock-based compensation from GAAP operating expense results in a range of $550 million to $600 million.

現在談到我們 2025 年的財務指導，我們預計我們的 GAAP 營運費用（包括研發和銷售、一般及行政費用）將在 6.7 億美元至 7.1 億美元之間。包含在 GAAP 營運費用中的股票薪酬預計在 1.1 億美元至 1.2 億美元之間。如果從 GAAP 營業費用中剔除股票薪酬，則該數字將在 5.5 億美元至 6 億美元之間。

Our capital allocation priorities remain the same and our resources will be focused on the following. First, on preparing for the potential US commercial launch of aficamten in September of this year, including the hiring of up to 150 sales reps in the US in the third quarter of 2025. Second, on advancing our pipeline with important label expansion opportunities for aficamten and clinical trials of omecamtiv mecarbil and CK-586 and third, on investments in our muscle biology platform.

我們的資本配置重點保持不變，我們的資源將集中在以下方面。首先，為今年 9 月在美國商業推出 aficamten 做準備，包括在 2025 年第三季在美國招聘多達 150 名銷售代表。第二，透過 aficamten 的重要標籤擴展機會以及 omecamtiv mecarbil 和 CK-586 的臨床試驗來推進我們的產品線；第三，對我們的肌肉生物學平台進行投資。

The anticipated year-over-year growth in operating expense will primarily be driven by the investments toward commercial readiness for the potential launch of aficamten for patients with obstructive HCM. Our strong balance sheet and access to further capital position us well to execute on our strategy, which we believe could lead to sustainable growth driven by specialty cardiology franchise.

預計營業費用年增率主要源自於為治療阻塞性 HCM 患者而可能推出的 aficamten 的商業化準備進行的投資。我們強大的資產負債表和進一步的資本獲取能力使我們能夠很好地執行我們的策略，我們相信這可以帶來由專業心臟病學特許經營推動的可持續成長。

With that, I'll hand it back to Robert.

說完這些，我就把它交還給羅伯特。

Thank you, Sung. Our progress in the fourth quarter 2024 has set the stage for a pivotal year ahead as we approach the potential US approval and commercial launch of aficamten in 2025, we are strategically aligning our longer-term vision while sharpening our operational focus for near term milestones and progress. With the right infrastructure, capabilities, partners and team in place, we are confident in our ability to execute and achieve multiple successes within our growing reach.

謝謝你，宋。我們在 2024 年第四季的進展為未來的關鍵一年奠定了基礎，因為我們即將在 2025 年獲得美國批准和商業推出 aficamten，我們正在策略性地調整我們的長期願景，同時加強我們的營運重點以實現近期里程碑和進展。憑藉合適的基礎設施、能力、合作夥伴和團隊，我們有信心在不斷擴大的業務範圍內執行並取得多項成功。

Earlier this year, we laid out our Vision 2030, our five-year strategic objectives designed to propel Cytokinetics to become the leading muscle focused specialty biopharmaceutical company intent on meaningfully improving the lives of patients through global access to innovative medicines. Vision 2030 serves as an aspirational roadmap made up of five objectives: innovation, ignition, impact, inspiration and ingenuity. These objectives articulate how we want to deliver product approvals, achieve broader access to our medicines, promote more equitable access and advance our pioneering research to benefit patients, shareholders and employees.

今年早些時候，我們制定了“2030 願景”，這是我們的五年戰略目標，旨在推動 Cytokinetics 成為領先的專注於肌肉治療的專業生物製藥公司，致力於通過全球範圍內獲得創新藥物，切實改善患者的生活。2030年願景是一份理想路線圖，由五個目標組成：創新、點燃、影響、啟發和獨創性。這些目標闡明了我們希望如何獲得產品批准、實現更廣泛地獲得我們的藥品、促進更公平的獲取以及推進我們的開創性研究以造福患者、股東和員工。

Aligned with this vision for our future, we recently announced the appointment of Robert Landry to our Board of Directors. Bob brings over three decades of financial and operational expertise in the pharmaceutical industry, most recently serving as Regeneron's Chief Financial Officer for 11 years, during which time he helped guide the company as it scaled and commercialized medicines globally. We're pleased to have him join our Board at this time in our corporate development.

為了實現這個未來願景，我們最近宣布任命羅伯特·蘭德里 (Robert Landry) 為董事會成員。鮑伯在製藥業擁有超過 30 年的財務和營運經驗，最近擔任再生元公司財務長長達 11 年，在此期間，他幫助指導公司在全球擴大和商業化藥品。我們很高興他在我們公司發展的這個時刻加入我們的董事會。

Looking at the year ahead in 2025, we will continue to focus on FDA approval and US Commercial launch readiness for aficamten and the execution of our ongoing clinical trials programs. Last year, we raised over $1 billion between existing cash and access to new capital and which affords us the runway to execute the US launch of aficamten, while also advancing our R&D pipeline and making investments in a fiscally prudent capital efficient way to build enduring value for shareholders. I'm optimistic about what our future holds in 2025.

展望 2025 年，我們將繼續關注 FDA 批准和美國商業上市對 aficamten 的準備以及我們正在進行的臨床試驗計劃的執行。去年，我們在現有現金和新資本之間籌集了超過 10 億美元，這為我們在美國推出 aficamten 提供了平台，同時也推進了我們的研發管道，並以財政審慎、資本高效的方式進行投資，為股東創造持久價值。我對 2025 年的未來充滿樂觀。

So now I'll recap our upcoming milestones. For aficamten, we expect to advance NDA review activities with FDA to support the potential US approval of aficamten in the second half of this year. We expect to advance go-to-market strategies and prepare to commercially launch aficamten in the US in the second half of this year subject to approval by the FDA. We expect to continue go-to-market plans in Germany and expand commercial readiness activities in Europe in 2025 in preparation for potential approval by the EMA in the first half of 2026.

現在我將回顧我們即將實現的里程碑。對於阿菲卡姆汀，我們預計將與 FDA 推進 NDA 審查活動，以支持今年下半年美國可能批准阿菲卡姆汀。我們預計將推動市場進入策略，並準備在今年下半年獲得 FDA 批准後在美國推出 aficamten。我們預計在 2025 年繼續在德國實施上市計劃，並擴大在歐洲的商業準備活動，為 2026 年上半年獲得 EMA 的批准做準備。

We expect to coordinate with Sanofi to support the potential approval of aficamten in China in the second half of 2025 pending approval by the NMPA. And we expect to report top line results from MAPLE-HCM in Q2 of this year. We also expect to complete enrollment of ACACIA-HCM in the second half of this year and to complete enrollment of the adolescent cohort in CEDAR-HCM also in the second half of 2025. For omecamtiv mecarbil, we expect to continue patient enrollment in COMET-HF through 2025 to enable completion of enrollment in 2026.

我們預計將與賽諾菲協調，以支持阿菲卡汀在 2025 年下半年獲得中國國家藥品監督管理局的批准。我們預計將在今年第二季報告 MAPLE-HCM 的頂線業績。我們也預計將在今年下半年完成 ACACIA-HCM 的招生，並在 2025 年下半年完成 CEDAR-HCM 的青少年群體招生。對於 omecamtiv mecarbil，我們預計在 2025 年之前繼續在 COMET-HF 中招募患者，以便在 2026 年完成招募。

For CK-586, we expect to complete enrollment of the first two patient cohorts in AMBER-HFpEF in the second half of this year. And for CK-089, we expect to complete the Phase 1 study this year. And finally for our preclinical development and ongoing research, we expect to continue ongoing preclinical development and research activities directed to additional muscle biology focused programs.

對於 CK-586，我們預計在今年下半年完成 AMBER-HFpEF 前兩組患者的招募。對於 CK-089，我們預計今年完成第一階段研究。最後，對於我們的臨床前開發和正在進行的研究，我們希望繼續進行更多肌肉生物學重點項目的臨床前開發和研究活動。

Operator, with that, we can now open the call to questions, please.

接線員，好了，我們現在可以開始提問了。

(Operator Instructions) Paul Choi, Goldman Sachs.

（操作員指示）高盛的 Paul Choi。

Hi, everyone. Good afternoon to you too. This is Kahlil calling in for Paul. I guess our question could be on MAPLE-HCM. If the results are positive, how should we think about the timeline for potential label expansion assuming approval in September? And then how would the positive results fit into the company's marketing strategy in the interim? Thank you so much.

大家好。祝你下午好。我是卡利爾 (Kahlil)，替保羅 (Paul) 打來的。我想我們的問題可能是關於 MAPLE-HCM 的。如果結果是正面的，假設 9 月獲得批准，我們應該如何考慮潛在標籤擴展的時間表？那麼，這些正面成果如何與公司在此期間的行銷策略相適應呢？太感謝了。

So I'll turn first to Fady to answer the first part and then to Andrew the second part please.

因此，我會先請 Fady 回答第一部分，然後請 Andrew 回答第二部分。

Yes, hi. I think in terms of timing to label expansion, we would certainly be looking to at the results and deciding whether to -- with the timing for that, I would expect it to come into 2026 as opposed to 2025, given our PDUFA date right now is September 26, 2025. But I think it all depend on timing and whatever else is going on at that time.

是的，你好。我認為，就標籤擴展的時間而言，我們肯定會關注結果並決定是否 - 考慮到時間安排，我預計它將在 2026 年而不是 2025 年實現，因為我們目前的 PDUFA 日期是 2025 年 9 月 26 日。但我認為這完全取決於時機以及當時發生的其他事情。

And in terms of the marketing strategy, the second study really offers confirmatory evidence of a primary study, both safety and efficacy, which is reassuring to physicians seeing a lot of the same primaries and secondaries. It opens up a cohort of cardiologists who really treat with beta blockers alone. There's really about 2,000 cardiologists of 500 or with some vast majority of prescribers of CMI today. And per our market research, this would open up to more prescribers who many of them feel like maybe beta blockers is good enough. And it offers that additional evidence and maybe even influencing guidelines and move treatment to first line over time, but that certainly takes a lot longer.

就行銷策略而言，第二項研究確實提供了主要研究的確認證據，包括安全性和有效性，這讓看到許多相同的主要研究和次要研究的醫生感到放心。它開闢了一批真正單獨使用β受體阻斷劑治療的心臟科醫生。目前，大約有 2,000 名心臟科醫生，佔 500 名 CMI 處方者的絕大多數。根據我們的市場調查，這將吸引更多的處方醫生，他們中的許多人認為β受體阻斷劑可能已經足夠了。它提供了額外的證據，甚至可能影響指導方針並隨著時間的推移將治療轉移到第一線，但這肯定需要更長的時間。

Maybe ask what Andrew is saying. Sorry, just to comment to Andrews. I do believe that MAPLE-HCM were to be positive could contribute to more category growth as potentially more cardiologists would be more comfortable prescribing a cardiac myosin inhibitor. And on top of that we would hope it would add to more category penetration for aficamten into that larger market. But I would consider it more incremental than transformative to what we would hope would be the label opportunity provided by SEQUOIA-HCM.

也許可以問問安德魯在說什麼。抱歉，只是想對安德魯斯發表評論。我確實相信，如果 MAPLE-HCM 能夠發揮積極作用，那麼它可能會促進更多類別的成長，因為更多的心臟科醫生可能會更願意開立心臟肌球蛋白抑制劑。最重要的是，我們希望它能增加 aficamten 在更大市場中的品類滲透率。但我認為，對於我們所希望的 SEQUOIA-HCM 提供的標籤機會而言，它更多的是一種漸進而非變革。

Great. Thank you.

偉大的。謝謝。

Thank you.

謝謝。

Cory Kasimov, Evercore ISI

Cory Kasimov，Evercore ISI

Hey, good afternoon. Thanks for taking the question. So following up on Andrew's prepared comments on market expansion, I think it's pretty well established that HCM is a highly under diagnosed condition. So curious, as to your expectations as to how this changes over time when there's two companies on the market educating and promoting the benefits of cardiac myosin inhibitors. If it really is on the order of 70% to even 80% percent of patients as yet undiagnosed, is there a good proxy of where this rate may get to say 3 to 5 years from now? Thank you.

嘿，下午好。感謝您回答這個問題。因此，根據安德魯關於市場擴張的準備好的評論，我認為已經充分證實 HCM 是一種嚴重未被診斷出來的疾病。我很好奇，當市場上有兩家公司宣傳和推廣心臟肌球蛋白抑制劑的益處時，您對這種情況如何隨時間變化的期望是什麼。如果確實有 70% 甚至 80% 的患者尚未得到診斷，那麼有沒有一個很好的指標可以預測 3 至 5 年後這一比例會達到什麼程度？謝謝。

Thank you. I'll turn to Andrew, please.

謝謝。請轉至安德魯。

Sure. It's a great question. I think as you know, when guidelines get adjusted, when studies are out, when us and others are at congresses where physicians go to learn about emerging data, those certainly increase penetration of market and increased diagnosis with awareness and education. I think what we've seen over the last few years is obstructive HCM has continued to increase diagnosis rates around with population, but the non-obstructive is growing at a double-digit rate.

當然。這是一個很好的問題。我認為，如你所知，當指導方針得到調整時，當研究結果出來時，當我們和其他人參加醫生大會以了解新興數據時，這些肯定會增加市場滲透率，並透過意識和教育提高診斷率。我認為我們在過去幾年中看到的是，阻塞性 HCM 的診斷率隨著人口的增長而持續增加，但非阻塞性 HCM 的診斷率正以兩位數的速度增長。

So I think over time, non-obstructive maybe even 50-50 or slightly larger than obstructive in terms of overall patient population. The estimate we have right now is about 30% or so of the population is diagnosed. And given these rates and kind of where they're going, that certainly could be in the fifty percent range in the next say three to five years.

因此我認為隨著時間的推移，就整體患者人數而言，非阻塞性​​患者人數可能與阻塞性患者人數各佔一半，或略多。我們目前的估計是大約有 30% 的人口被診斷出患有這種疾病。考慮到這些利率和未來的走勢，未來三到五年內，這一比例肯定會達到 50% 左右。

In terms of comps, we're reviewing the landscape as well. And I do believe that the amyloidosis space and the pulmonary arterial hypertension space both afford comps in terms of what a next in class drug could mean in terms of increased diagnosis and also category penetration. We look at those as good proxies.

就同​​類產品而言，我們也在審查其市場狀況。我確實相信，澱粉樣變性領域和肺動脈高壓領域都具有可比性，因為下一代藥物在提高診斷率和類別滲透率方面具有可比性。我們認為這些是很好的代理。

All right. Sounds good. Appreciate it. Thanks, guys.

好的。聽起來不錯。非常感謝。謝謝大家。

Thank you.

謝謝。

Salim Syed, Mizuho.

薩利姆賽義德，瑞穗。

Hello, Salim.

你好，薩利姆。

Hey, Robert. Thanks for the question. One question we're getting a lot on, I'm sure you guys are as well, I would just love to get your view, is just the upcoming Edgewise dataset, the 28-day. We just sort of look to see how your framework in it, anything you're looking out for there?

嘿，羅伯特。謝謝你的提問。我們常被問到的一個問題，我相信你們也是一樣，我很想聽聽你們的看法，就是即將發布的 Edgewise 資料集，也就是 28 天的資料集。我們只是想看看您的框架在其中是怎樣的，您在那裡尋找什麼？

And also, just related to that, do you think there's any even remote possibility that they if they were to progress come out of this without any REMS at all? Thank you, based on the preclinical data at least. Thank you.

而且，與此相關的是，您是否認為，如果他們要取得進展，有沒有可能完全不使用任何 REMS？謝謝，至少基於臨床前數據。謝謝。

Yes, it's a very slippery slope obviously that we won't go down to comment on another company's ongoing development program. But I still appreciate the question. With that said, it's early days and I'll turn to Fady to comment on this matter much as he has been asked by others, but I would suggest that we let the data and evidence speak for itself. Fady?

是的，這顯然是一個非常危險的舉動，我們不會去評論另一家公司正在進行的開發計畫。但我仍然很感謝你提出這個問題。話雖如此，現在還為時過早，我會讓 Fady 對此事發表評論，就像其他人問過他一樣，但我建議我們讓數據和證據來說話。法迪？

Yes. Hi, Salim. I think it's still, as Robert said, early in the program, I think in order to understand the safety profile of the drug that's going to be used in thousands of people, you're going to need hundreds of people's worth of data. And until you understand that, it's premature to comment, even if I were to comment on their eventual safety profile and monitoring. So I'll probably just leave it there.

是的。你好，薩利姆。我認為，正如羅伯特所說，在專案早期，為了了解將在數千人中使用的藥物的安全性，您將需要數百人的數據。在您理解這一點之前，現在發表評論還為時過早，即使我要評論他們最終的安全狀況和監控。所以我可能就把它留在那裡了。

We're looking forward to seeing the data. Obviously, these data will be telling as to whether there is an opportunity to land a new mechanism treatment in oHCM that would be potentially differentiated. We're very pleased with the data we have supporting aficamten both as it relates to efficacy as well as safety, ease of use and other things that were designed into aficamten consistent with intrinsic properties. And as we look forward to potential approval and potential commercial launch, we're very confident that we're situated in a very positive place. With that said, we'll take a look at these data as they may come out later, I guess, in the first quarter from what we gather.

我們期待看到數據。顯然，這些數據將告訴我們是否有機會在 oHCM 中找到一種具有潛在差異化的新機制治療方法。我們對支援 aficamten 的數據感到非常滿意，因為它涉及功效、安全性、易用性以及與 aficamten 的內在特性一致的其他方面。當我們期待潛在的批准和潛在的商業發佈時，我們非常有信心我們處於非常積極的位置。話雖如此，我們還是會查看這些數據，因為根據我們收集到的信息，我猜它們可能會在第一季稍後公佈。

Okay, perfect.

好的，完美。

Thank you so much. Thank you.

太感謝了。謝謝。

James Condulis, Stifel

詹姆斯·康杜利斯（Stifel）

Good afternoon. Thanks for taking my question and congrats on all the progress. I just want to ask one kind of quick question on the REMS and totally appreciate there's only so much you can say, but wanted to get your thoughts on if you expect mavacamten's REMS to be eased in The U. S. As well and sort of if that happens like how does that change how you sort of think about the range of scenarios for kind of what aficamten 's REMS looks like?

午安.感謝您回答我的問題，並祝賀您取得的所有進展。我只想問一個關於 REMS 的快速問題，我完全理解您能說的只有這麼多，但我想聽聽您的看法，您是否預計美國也會放寬 mavacamten 的 REMS？如果這種情況真的發生，這會如何改變您對 aficamten 的 REMS 的各種情景的看法？

Again, sort of like in that scenario, would you define differentiated REMS as still differentiated in sort of the maintenance setting as well? Or does that become more about some of the other aspects of the REMS? Just curious what you can share there. Thanks.

再次，有點像在那種情況下，您是否會將差異化的 REMS 定義為在維護設定中仍然具有差異化？或者這是否更多地涉及 REMS 的其他一些方面？只是好奇您可以在那裡分享什麼。謝謝。

Yes, here again, I'm going to be careful not to make any comparative statements. But I will say we noted with interest the BMS earnings call and its reporting on the changes as it relates to EMA label and we look forward to learning I guess in Q2 how FDA may respond to an application to ease certain restrictions relating to the existing REMS for mavacamten, Camzyos.

是的，在這裡我再次要小心，不做任何比較性的陳述。但我要說的是，我們饒有興趣地註意到了 BMS 收益電話會議及其有關與 EMA 標籤相關的變化的報告，我們期待在第二季度了解 FDA 將如何回應一項申請，以放寬與 mavacamten、Camzyos 現有 REMS 相關的某些限制。

We've done a lot of market research and there are points of differentiation that we continue to believe are quite meaningfully important for aficamten as are consistent with intrinsic properties. And echo frequency is one of those, but so are there several others. And maybe I'll ask Andrew to comment on the market research we've done and our expectations for a differentiated risk mitigation profile if approved.

我們做了大量的市場調查，我們仍然相信，對於 aficamten 來說，差異點非常重要，因為它們與內在屬性一致。迴聲頻率就是其中之一，但還有其他幾個頻率。也許我會請安德魯對我們所做的市場研究以及如果獲得批准，我們對差異化風險緩解概況的期望發表評論。

Thanks, Robert. So differentiation, I mean, maybe we'll just start with the data. The data should inform the label the label, which is our guidelines for claims around differentiation. There are many aspects of differentiation that we're exploring and that are going well from a market research point of view. So this could be one of them or this could be in parallel, but there's others.

謝謝，羅伯特。所以區分，我的意思是，也許我們只是從資料開始。數據應該告知標籤，這是我們針對差異化聲明的指導方針。我們正在探索差異化的許多方面，從市場研究的角度來看，進展順利。因此，這可能是其中之一，也可能是並行的，但還有其他的。

I think if this does get relaxed for the whole category, this is actually good for the category. The vast majority of patients are not treated today with a CMI. If less frequent monitoring in the maintenance phase gets more patients on board with the CMI, gets more physicians to treat with the CMI, it's kind of high tide lifts all both. So, we look forward to what the FDA has to say. I believe the date is April and we'll certainly go from a differentiation given how our label is informed by the data.

我認為，如果整個類別確實放寬了這個限制，這實際上對該類別來說是件好事。如今，絕大多數患者並未接受 CMI 治療。如果維持階段的監測頻率較低，可以讓更多的患者接受 CMI，讓更多的醫生使用 CMI 進行治療，那麼這對兩者都是一種提升。因此，我們期待 FDA 的回應。我相信日期是四月，考慮到我們的標籤是如何根據數據得出的，我們肯定會從差異化的角度出發。

We've said this many times that our goal is to ensure that more cardiac myosin inhibitors are used by more cardiologists for more patients. And still to our estimates, there are over 80% of eligible patients who could stand to benefit from use of a cardiac myosin inhibitor and with prevalence growing that number increases. We believe strongly that aficamten if approved will have a differentiated profile, both as it relates to label and risk mitigation. So we'll wait and see, but I hope that answers your question.

我們已經多次說過，我們的目標是確保更多的心臟科醫生為更多的患者使用更多的心肌肌球蛋白抑制劑。據我們估計，超過 80% 的合格患者可以從使用心肌肌球蛋白抑制劑中受益，而且隨著盛行率的增加，這個數字還會增加。我們堅信，如果獲得批准，aficamten 將在標籤和風險緩解方面具有差異化優勢。所以我們拭目以待，但我希望這能回答你的問題。

Yes, I appreciate the color. Thank you.

是的，我很欣賞這個顏色。謝謝。

Tess Romero, JPMorgan

泰絲羅梅羅，摩根大通

Hi, Robert and team. Thanks for taking our questions tonight and look forward to ACC. So do you think based on your physician and KOL interactions that it is appreciated that there is not the same pharmacogenomic and DDI liability with aficamten as there is with Camzyos due to the way that the drug is metabolized related to a patient's CYP2C19 genotype versus yours?

嗨，羅伯特和他的團隊。感謝您今晚回答我們的問題，並期待 ACC。那麼，您是否認為，根據您的醫生和 KOL 的互動，可以認識到，由於藥物代謝方式與患者的 CYP2C19 基因型有關，而與您的 CYP2C19 基因型不同，aficamten 並不具有與 Camzyos 相同的藥物基因組學和 DDI 責任？

If not, how do you think you will go about educating doctors around this point? And then relatedly, to be clear, will any monitoring be needed by the pharmacy around concomitant meds with aficamten? Thanks so much.

如果沒有，您認為您將如何針對這一點對醫生進行教育？然後相關地，需要明確的是，藥房是否需要對與阿菲卡汀同時使用的藥物進行任何監測？非常感謝。

Good questions. Maybe I'll ask Fady and Stuart to comment and then Andrew if he wants to add anything.

好問題。也許我會請 Fady 和 Stuart 發表意見，然後請 Andrew 補充一些內容。

I think, Jess, your question really ultimately is going to depend on the labeling that we achieved with aficamten, but the, I think physicians that we've interacted with, even that have conducted our clinical trials, recognize a difference, say, that the drug interaction profile of aficamten doesn't involve 2C19, that it has a very few meaningful drug interactions, and certainly have been educated to that fact and act accordingly.

傑西，我認為你的問題最終將取決於我們對阿菲卡汀的標籤，但我認為與我們互動過的醫生，甚至進行過臨床試驗的醫生，都認識到了其中的區別，比如，阿菲卡汀的藥物相互作用概況不涉及 2C19，它具有極少有意義的藥物相互作用，他們肯定已經了解了這一事實並採取了相應的行動。

The monitoring of concomitant medications is something that's always done. There's no drug the universe that is not susceptible at all to any drug interactions even aficamten, but any drug interactions we have would be reasonably rare and uncommon, and physicians would be educated on those as well. But I doubt that there's necessarily need for a monitoring program or anything like that. We haven't done that in our clinical trials and haven't had any issues to date.

伴隨用藥的監測是始終需要進行的工作。宇宙中沒有任何藥物完全不受任何藥物交互作用的影響，即使是 aficamten，但我們所遇到的任何藥物交互作用都相當罕見且不常見，醫生也會接受有關這些方面的教育。但我懷疑是否真的需要監控程式或類似的東西。我們在臨床試驗中沒有這樣做過，到目前為止也沒有遇到任何問題。

For clarification, you asked about pharmacy. Stuart or Andrew, do you want to comment on that? Pharmacy.

為了澄清起見，您詢問了藥房的情況。斯圖爾特或安德魯，你們想對此發表評論嗎？藥局。

I mean, we're not expecting I think in our base case that a from any REMS program that pharmacy monitoring would be part of a REMS program where a pharmacy has to call a patient and talk about existing drugs and potential drug interactions. That is not something that we're anticipating.

我的意思是，我認為在我們的基本情況下，我們並不期望任何 REMS 計劃中的藥房監控都成為 REMS 計劃的一部分，在該計劃中，藥房必須致電患者並討論現有藥物和潛在的藥物交互作用。這不是我們所期待的。

Thank you, guys.

謝謝你們。

Leonid Timashev, RBC Capital Markets

Leonid Timashev，加拿大皇家銀行資本市場

Good afternoon, guys. Yes. Thanks for taking my I wanted to ask on the endpoints for ACACIA and maybe some comparisons to the competitor in HCM study. And I don't mean a corner unit commenting on someone else's study, but can you talk about any potential differences in KCCQ-23 versus KCCQ-12? And maybe why you settled on a single primary focusing on KCCQ rather than also including pVO2 as a primary and sort of whether that was based on your own diligence of your own data or in consultation with the FDA? Just any thoughts, I would appreciate it. Thank you.

大家下午好。是的。感謝您接受我的詢問，我想詢問一下 ACACIA 的終點以及與 HCM 研究中的競爭對手的一些比較。我並不是指角落單元評論別人的研究，而是你能談談 KCCQ-23 與 KCCQ-12 之間的任何潛在差異嗎？也許您為什麼選擇將 KCCQ 作為主要關注點，而不是將 pVO2 作為主要關注點，這是否是基於您自己對數據的盡職調查，還是與 FDA 協商後做出的？只要有任何想法，我都會很感激。謝謝。

Sure. I'll ask Fady and also Stuart if he wants to comment.

當然。我會詢問 Fady 和 Stuart 是否願意發表評論。

Well, let me say, I think the KCCQ is a patient reported outcome. We examined its impact the impact of aficamten on KCCQ in our Phase 2 study in nHCM. And while that was an open label experience, there was a meaningful impact on KCCQ. That said, I think that regulators in general would like to see an impact of a drug on more than just KCCQ. They like to see improvements in exercise and in NYHA class, a consistency, if you will, across functional and symptomatic endpoints.

好吧，我想說，我認為 KCCQ 是患者報告的結果。我們在 nHCM 的第 2 階段研究中檢查了 aficamten 對 KCCQ 的影響。雖然這是一次開放標籤體驗，但對 KCCQ 產生了重大影響。話雖如此，我認為監管機構總體上希望看到一種藥物對 KCCQ 以外其他方面的影響。他們希望看到運動和 NYHA 等級的改善，如果願意的話，在功能和症狀終點方面保持一致。

And ACACIA is currently designed has both. It has an exercise endpoint as a secondary endpoint as KCCQ as a primary endpoint. As you pointed out, ODYSSEY has a dual primary endpoint with both Peak VO2 and KCCQ in parallel, assessed as part of a primary.

而ACACIA目前的設計正是兼具了這兩點。它以鍛鍊終點作為次要終點，以 KCCQ 作為主要終點。正如您所指出的，ODYSSEY 具有雙重主要終點，即峰值 VO2 和 KCCQ 同時存在，作為主要終點的一部分進行評估。

I think practically speaking, there's not that much of a difference between the two approaches. They both are both designed to assess the strength of the evidence with respect to patient reported outcome and other functional metrics. And I think regulators clearly want to see a consistency across those both of those domains. Hopefully that answers your question, Leo.

我認為從實際角度來說，這兩種方法之間並沒有太大的差異。它們都旨在評估與患者報告的結果和其他功能指標相關的證據的強度。我認為監管機構顯然希望看到這兩個領域的一致性。希望這能回答你的問題，Leo。

That's great. Thank you.

那太棒了。謝謝。

Akash Tewari, Jefferies.

Akash Tewari，傑富瑞。

Hi. This is Zaki on for Akash. Thanks so much for taking the question. So in terms of non-obstructive HCM, so it looks like Bristol's ODYSSEY and your ACACIA trial, you're both looking to dose patients up to achieve higher exposures. And so when I look at Redwood cohort 4, it looks like the final proBNP levels are similar to MAVERICK's lower dose cohort. But I think the key question is whether you can actually show more efficacy by getting patients onto the 20 mg dose in ACACIA.

你好。這是 Zaki 代替 Akash 上場的。非常感謝您回答這個問題。因此，就非阻塞性 HCM 而言，布里斯託的 ODYSSEY 和您的 ACACIA 試驗似乎都希望增加患者的劑量，以獲得更高的暴露量。因此，當我查看 Redwood 隊列 4 時，看起來最終的 proBNP 水平與 MAVERICK 的低劑量隊列相似。但我認為關鍵問題是讓患者服用 20 毫克劑量的 ACACIA 是否真的能顯示出更高的療效。

So based on like the SEQUOIA data you've seen so far, how easily do you think you can actually keep patients on the 20 mg dose without EF issues for like the whole 36-week period? And also, is there any sense on whether slower titration like we're seeing in ODYSSEY might be better in the nHCM population?

那麼，根據您目前看到的 SEQUOIA 數據，您認為如何讓患者在整個 36 週內持續服用 20 毫克劑量且不出現 EF 問題？此外，我們在 ODYSSEY 中看到的較慢滴定是否對 nHCM 族群更有利？

That's a multipart question and I'll ask Fady and Stuart to tackle it.

這是一個由多部分組成的問題，我會請 Fady 和 Stuart 來解決這個問題。

Well, maybe I'll take it. I think just to be simple and concise, the REDWOOD data, we dosed patients between 5 mg and 15 mg, 85% of patients got up to 15 mg and were there within six weeks of initiation of therapy, many of those patients were still eligible to up titrate to 20 mg. And I don't think fundamentally there's any difference between the cardiac function of an nHCM patient and an oHCM patient. So, one could expect a similar dose distribution in the two groups perhaps even a bit skewed to the high side in NHM because you don't stop titrating based on achieving the targets with respect to gradients.

好吧，也許我會接受它。我認為，簡單來說，根據 REDWOOD 數據，我們給患者服用 5 毫克至 15 毫克之間的劑量，85％ 的患者在開始治療後六週內劑量增加到 15 毫克，其中許多患者仍有資格增加到 20 毫克。我認為 nHCM 患者和 oHCM 患者的心臟功能從根本上沒有任何區別。因此，可以預期兩組的劑量分佈相似，甚至可能在 NHM 中略微偏向高側，因為您不會根據梯度實現目標而停止滴定。

And what we saw in REDWOOD was that NT-proBNP decreased in a dose dependent manner, the higher doses produced greater decrements in NT-proBNP. And so I think the strategy that we've adopted in ACACIA is built very tightly on what we did in REDWOOD, right? It's a one to one, the dosing strategy is almost the same, the speed of dosing is almost the same. And I think all of those things are helpful when you design a Phase 3 study on the basis of a Phase 2 study. So I think we're pretty confident with how we've addressed dosing in that trial.

我們在 REDWOOD 中看到，NT-proBNP 以劑量依賴性方式減少，劑量越高，NT-proBNP 的減少量越大。所以我認為我們在 ACACIA 中採用的策略與我們在 REDWOOD 中採取的策略緊密相關，對嗎？是一對一的，加藥策略幾乎是一樣的，加藥速度也幾乎是一樣的。我認為，當您在第 2 階段研究的基礎上設計第 3 階段研究時，所有這些都是有幫助的。所以我認為我們對該試驗中如何解決劑量問題非常有信心。

Thank you, guys so much.

非常感謝你們。

David Lebowitz, Citi

花旗銀行 David Lebowitz

Hi. This is [Ike Lee] on for David Lebowitz. Thanks for taking the question. We are wondering if you can orient us on expectations, particularly on the exercise capacity primary endpoint heading into the MAPLE-HCM read out. Are we looking for a similar level of benefit this time head-to-head versus beta blockers as we did in SEQUOIA, something like 5% to 8%, maybe 10% improvement over baseline exercise capacity? And is there any change in the level of clinical meaningfulness for this one as opposed to the trials run before since the endpoint is the same? Thanks.

你好。這是 [Ike Lee] 為 David Lebowitz 主持的。感謝您回答這個問題。我們想知道您是否可以為我們提供一些預期，特別是關於 MAPLE-HCM 讀數中的運動能力主要終點。我們這次是否希望與 β 受體阻斷劑進行正面交鋒時獲得與 SEQUOIA 類似的益處，即比基線運動能力提高 5% 到 8%，甚至 10%？由於終點相同，因此與先前進行的試驗相比，本次試驗的臨床意義水準是否有任何變化？謝謝。

Good questions. We'll probably want to answer them in terms of how the study was designed, what it was powered to demonstrate, and I'll ask Fady to comment on that please.

好問題。我們可能想從研究的設計方式、研究的目的來回答他們，我會請 Fady 對此發表評論。

Sure. So, MAPLE was designed as a trial with a to assess the impact of aficamten and metoprolol on exercise capacity and it's powered to about a 2.0 difference between the two. And as we had in SEQUOIA achieved 1.75, I think that's pretty reasonable expectation, 1.75 was very, very highly statistically significant.

當然。因此，MAPLE 被設計為一項試驗，用於評估阿非卡坦和美托洛爾對運動能力的影響，並且其功率為兩者之間的差異約為 2.0。正如我們在 SEQUOIA 中實現的 1.75 一樣，我認為這是相當合理的預期，1.75 具有非常非常高的統計意義。

I think when you get to questions of clinical meaningfulness, anything above 1 is thought to be clinically meaningful, and certainly the 1.74 that we achieved in SEQUOIA is we consider that clinically meaningful.

我認為，當你談到臨床意義的問題時，任何高於 1 的值都被認為具有臨床意義，當然，我們在 SEQUOIA 中取得的 1.74 就是我們認為具有臨床意義的。

There are data that show that mortality and morbidity are potentially tied to Peak VO2 and then changes in Peak VO2 of that magnitude have substantial impacts on long term morbidity and mortality. So I think any of those changes by 5% to 8%, 10% would represent clinically meaningful differences between the two.

有數據表明，死亡率和發病率可能與峰值攝氧量有關，而峰值攝氧量的這種幅度的變化會對長期發病率和死亡率產生重大影響。因此我認為任何 5% 到 8% 或 10% 的變化都代表兩者之間具有臨床意義的差異。

And again, as I said earlier, it's not necessarily just going to be all about what's the difference between Peak VO2, but it's going to be a consistency of treatment effect across endpoints. It's going to be safety. It's going to be tolerability. All of those things I think are should be considered in considering how aficamten performs as monotherapy compared to metoprolol performing as monotherapy. Thanks for the question.

正如我之前所說，這不一定只是關於峰值攝氧量之間的差異，而是跨終點的治療效果的一致性。這將是安全的。這將是可容忍的。我認為在考慮阿非卡坦作為單一療法的效果與美托洛爾作為單一療法的效果相比時，應該考慮所有這些因素。謝謝你的提問。

Sean McCutcheon, Raymond James

肖恩麥卡琴、雷蒙德詹姆斯

Hi, guys. Good afternoon and thanks for taking the question. Maybe to build on the last question. For MAPLE, you're enrolling patients with percent predicted Peak VO2 of less than 100%, whereas in SEQUOIA, for the most part, outside of one patient, you are enrolling less than 80% predicted. How should we be thinking of this patient population as it relates to obstruction driving exercise capacity deficits and how that contrasts with SEQUOIA, if at all? Thanks.

嗨，大家好。下午好，感謝您回答這個問題。也許可以基於最後一個問題。對於 MAPLE，您招募的患者峰值攝氧量預測百分比低於 100%，而在 SEQUOIA 中，大多數情況下，除了一名患者外，您招募的患者峰值攝氧量百分比低於預測值的 80%。我們應該如何看待這群患者，因為它與導致運動能力缺陷的阻塞有關，以及它與 SEQUOIA 有何不同（如果有的話）？謝謝。

Hi, this is Stuart Kupfer. I think that what we observed in SEQUOIA was that threshold less than 90% or less than 80 did not make significant difference in terms of the incapacity of these patients. I think it was apparent that because of the degree of obstruction and the fact that these patients were significantly symptomatic, they already had a significant deficit in their exercise capacity. So we just realized that we could relax that criteria and still enroll patients with quite significant deficit that we believe that aficamten that these patients could benefit from aficamten treatment.

你好，我是 Stuart Kupfer。我認為，我們在 SEQUOIA 中觀察到的是，低於 90% 或低於 80 的閾值對這些患者的無行為能力沒有顯著影響。我認為很明顯，由於阻塞程度和這些患者的明顯症狀，他們的運動能力已經有嚴重缺陷。因此，我們意識到我們可以放寬該標準，但仍然可以招募具有相當嚴重缺陷的患者，我們相信這些患者可以從治療中受益。

Srikripa Devarakonda, Truist Securities.

Sriripa Devarakonda，Truist 證券公司。

Hi, it's Alex on for Srikripa. Thanks. We are excited about the progress in 2025. One commercial question for us. We've heard with mavacamten that treatment by cardiologists and their practice centers may be limited to insufficient numbers of monitoring equipment to adjust the large volumes that they see, and patients have been referred to more specialist centers. Wanted to know on your end, have you heard this? Is there potential for future treatment with aficamten to be administered by a broader range of HCPs? And does your market research highlight any bottlenecks related to equipment readiness in target markets outside the US as well as the US?

大家好，我是 Srikripa 的 Alex。謝謝。我們對 2025 年的進展感到興奮。問我們一個商業問題。我們聽說，心臟科醫生及其診所的治療可能受限於監測設備數量不足以調整他們所看到的大量數據，因此患者已被轉診到更專業的中心。想知道你聽過這個嗎？未來是否有可能讓更廣泛的醫療保健提供者使用阿菲卡汀進行治療？您的市場研究是否強調了美國以外目標市場以及美國境內與設備準備相關的任何瓶頸？

Yes. So we noted your equity research analyst note to that effect and where some of the echo infrastructure was perhaps impeding adoption beyond centers of excellence. Maybe I'll ask Andrew to comment on what he's learned from market research with regard to that and how that may or may not extrapolate to learnings in Europe.

是的。因此，我們注意到您的股票研究分析師指出，一些迴聲基礎設施可能會阻礙卓越中心以外的採用。也許我會請安德魯評論他從市場研究中了解到了什麼，以及這些了解是否適用於歐洲的經驗。

So we looked at echo capacity across the US both within specialized centers, academic centers, city centers, as well as community. And it is currently not a burden or anything that's kind of reducing the capacity is not allowing patients to potentially get treated. So I think there's other challenges with starting treatment outside maybe academic centers and centers of excellence, but it's not related to echo capacity largely.

因此，我們研究了美國各地的迴聲容量，包括專業中心、學術中心、城市中心以及社區。目前，這還不算是一種負擔，也不算什麼降低治療能力的因素，也不會讓患者無法接受治療。因此，我認為在學術中心和卓越中心之外開始治療還有其他挑戰，但這與迴聲能力無關。

When we looked at Europe, Europe is a more concentrated market than US, typically Europe, you have to start in a hospital, in a community center. It's not as diverse in terms of the number of physician’s offices you have to go to, usually going actually to a center. And because Europe has a single payer system generally by country. And they as part of the reimbursement process for a specialty medication. It's pretty typical for prescribing to be limited to one of these institutions and these institutions have capacity as well.

當我們看歐洲時，歐洲是一個比美國更集中的市場，通常在歐洲，你必須從醫院、社區中心開始。就你必須去的醫生辦公室數量而言，情況並沒有什麼不同，通常實際上是去一個中心。而且由於歐洲一般都實行按國家劃分的單一付款人制度。它們是專科藥物報銷流程的一部分。處方通常僅限於其中一個機構，而這些機構也具有能力。

It's difficult sometimes to distinguish between what's cause and effect or which the cart and which is the horse. We do believe that a majority of Camzyos use currently is amongst a concentrated number of prescribers who happen to be in centers of excellence. And with more experience comes ability to navigate through a REMS program.

有時很難區分什麼是原因，什麼是結果，什麼是馬車。我們確實相信，目前大多數 Camzyos 使用者都是來自卓越中心的少數處方者。隨著經驗的增加，您將能夠更好地駕馭 REMS 程序。

So can you extrapolate that to mean that there's less of an issue outside of centers of excellence? We look at this as experience with cardiac myosin inhibitors in general is correlated with broader and more adoption of the existing cardiac myosin inhibitor. Our hope is if aficamten is approved that we can contribute to more education, more awareness, more category growth and expansion beyond centers of excellence as could be a rising tide to lift the class. And that could hopefully confer benefit to aficamten as we hope it becomes a category leader independent of what may be any concerns relating to echo capacity. I hope that helps.

那麼，您能否推斷這意味著卓越中心之外的問題較少？我們認為，總體而言，心臟肌球蛋白抑制劑的使用經驗與現有心臟肌球蛋白抑制劑的更廣泛和更多採用有關。我們希望，如果 aficamten 獲得批准，我們將能夠為更多的教育、更多的認識、更多的類別成長和超越卓越中心的擴展做出貢獻，從而成為提升階層的潮流。我們希望這能為 aficamten 帶來好處，因為它能夠成為類別領導者，而不受與迴聲容量相關的任何擔憂的影響。我希望這能有所幫助。

Yes, it makes a lot of sense and thanks. We're all looking towards the year ahead.

是的，這很有意義，謝謝。我們都對新的一年充滿期待。

Roanoke Ruiz, Leerink Partners

魯伊斯（Roanoke Ruiz），Leerink Partners

Good afternoon.

午安.

Hi, good afternoon, everyone. So slightly different question for me. I was curious if you could elaborate a bit more on your future goals for, I think you mentioned BD and corporate development in the coming years. It sounds like you're willing to consider augmenting your R&D pipeline, curious of any color on stage of asset, mechanisms, indications, etcetera that you'd be interested in internally or externally? And how would you balance that with your current cash runway expectations today?

大家好，下午好。所以對我來說這個問題稍微有點不同。我很好奇您是否可以更詳細地闡述您未來的目標，我想您提到了未來幾年的 BD 和企業發展。聽起來您願意考慮擴大您的研發管道，想知道您在內部或外部對資產、機制、指示等任何階段的顏色感興趣嗎？您如何平衡這與目前的現金流預期？

Yes. So I'll ask Isaac to comment first followed by Sung and then I may have a few comments after that.

是的。因此，我會先請 Isaac 發表評論，然後請 Sung 發表評論，之後我可能會發表一些評論。

Sure. Thanks so much for the question. The most important thing for us is to make sure that we continue to focus on our expertise in the muscle biology and be able to look at the landscape, both of what's being developed externally as well as internally to make sure that we can help advance the most advanced programs that are available. So from a licensing perspective, we have been and are actively I mean, discussions with both academics and research centers where there are preclinical programs, but also looking at early stage clinical development programs where we can use our own expertise to advance these programs forward.

當然。非常感謝您的提問。對我們來說，最重要的是確保我們繼續專注於我們在肌肉生物學方面的專業知識，並能夠觀察外部和內部正在開發的內容，以確保我們能夠幫助推進現有的最先進的項目。因此，從許可的角度來看，我們一直在積極地與擁有臨床前項目的學術機構和研究中心進行討論，同時也在研究早期臨床開發項目，我們可以利用自己的專業知識來推進這些項目的發展。

We're obviously looking at that from being prudent from a financial perspective and where we think we can have the greatest impact. Our focus has been on small molecules and as we've made comments earlier in our talk that being able to look at other modalities is something that is very important to us because we see that happening within the field and we want to make sure that we are in the forefront.

顯然，我們從財務角度謹慎地看待這個問題，並認為我們可以在這個問題上產生最大的影響。我們的重點一直放在小分子上，正如我們在之前的談話中所說的那樣，能夠研究其他模式對我們來說非常重要，因為我們看到該領域正在發生這種情況，我們希望確保我們處於領先地位。

Yes. And Roanoke, in terms of cash runway, we believe we have multiple years of runway as we start the year, and this is supported by our starting cash balance of $1.2 billion. Also, we have access to further capital, as you know, from Royalty Pharma up to $500 million. We'll also benefit from some near-term milestones from the BD deals we closed last year related to aficamten ex-US. So we're in a very strong position here.

是的。就羅阿諾克的現金流而言，我們相信，從今年開始，我們擁有多年的現金流，而這要歸功於我們 12 億美元的初始現金餘額。此外，如您所知，我們還可以從 Royalty Pharma 獲得高達 5 億美元的額外資金。我們也將受益於去年與美國以外地區的 aficamten 相關的 BD 交易的一些近期里程碑。因此，我們在這裡處於非常有利的地位。

Specific to this year, we expect cash utilization to be in the low $500 million. So you can kind of work out the math there that with all the things that I've described in terms of sources of capital, we believe we have multiple years on the runway right now.

具體到今年，我們預期現金利用率將在 5 億美元以下。因此，您可以計算一下，根據我所描述的所有資金來源，我們相信我們現在已經擁有多年的營運經驗。

And just to elaborate a little bit, our focus to be clear remains on aficamten and our later stage pipeline and that's where our investment capital is best deployed. The things that Isaac was referring to are more intentional to augment, complement and provide adjacency to things we're doing in earlier stage of our research and the capital investments alongside of that will be modest relative to the overall spend.

稍微詳細一點，我們的重點仍然明確在 aficamten 和我們的後期管道上，這也是我們的投資資本最佳部署的地方。艾薩克所指的事情更有意圖地增強、補充和提供與我們在研究早期階段所做的事情的相鄰性，而與此同時的資本投資相對於總體支出而言將是適度的。

So this is more about building training wheels for Cytokinetics as we want to execute on our Vision 2030 alongside of the things we're doing organically to provide some inorganic complement especially as could be adjacent to things we're already doing where we can mitigate risk and with new modalities enable a transition to some non-small molecule approaches. Don't confuse that to mean we're going to go into more expensive modalities like gene therapies and cell therapies that's not our intention.

因此，這更多的是為 Cytokinetics 構建訓練輪，因為我們希望在執行我們的 2030 願景的同時，也進行一些有機補充，特別是因為可以與我們已在做的事情相鄰，我們可以在其中降低風險，並通過新的方式過渡到一些非小分子方法。請不要誤以為我們會採用基因療法和細胞療法等較昂貴的療法，這不是我們的本意。

Understood. Thanks.

明白了。謝謝。

Thank you.

謝謝。

Joe Pantginis, H.C. Wainwright.

喬·潘吉尼斯（H.C.）溫賴特。

Hello, Joe.

你好，喬。

Hey, everybody. Thank you for taking the question. Good afternoon. So I'm not sure if you could discuss this right now because everything is active. But upcoming to your mid cycle meeting with the FDA, anything you could discuss about key questions that are still outstanding or any potential rate limiting steps?

嘿，大家好。感謝您回答這個問題。午安.所以我不確定你現在是否可以討論這個問題，因為一切都很活躍。但是，在您與 FDA 舉行中期會議之前，您可以討論尚未解決的關鍵問題或任何潛在的限速措施嗎？

And then also with regard to omecamtiv, something anything you might be that you can share regarding COMET-HF and the enrollment trajectory, say, related to GALACTIC, since there are additional screening criteria? Thanks.

然後關於 omecamtiv，您可以分享一些有關 COMET-HF 和招生軌蹟的資訊嗎，例如與 GALACTIC 相關的信息，因為還有其他篩選標準？謝謝。

Sure. So you answered your own question with respect to ongoing FDA interactions. We can't really comment other than to say that we feel very good about how we're situated in light of the ongoing activities. And as we approach a mid-cycle meeting, we believe we're in a good position to address any questions we may be getting from FDA. As it relates to comment and enrollment sites relative to GALACTIC, maybe I could ask Fady or Stuart to comment on that.

當然。因此，您就正在進行的 FDA 互動回答了您自己的問題。我們真的無法發表評論，只能說，鑑於正在進行的活動，我們對自己的處境感到非常滿意。隨著中期會議的臨近，我們相信我們能夠很好地回答 FDA 可能提出的任何問題。由於它與 GALACTIC 的評論和註冊網站有關，也許我可以請 Fady 或 Stuart 對此發表評論。

Thanks, Joe. So as you know, we began enrollment in COMET-HF late last year. And we have an advantage of leveraging all the information we have from GALACTIC in terms of the best investigators to participate in the trial. And we have the advantage of a great data set to draw from demonstrating the, I think, the hypothesis that omecamtiv mecarbil will be even more effective in these higher risk patients.

謝謝，喬。如您所知，我們在去年年底開始招募 COMET-HF 人員。我們的優勢在於能夠利用 GALACTIC 提供的所有資訊來選擇最優秀的研究人員參與試驗。我們擁有大量數據的優勢，可以證明 omecamtiv mecarbil 對這些高風險患者更有效的假設。

And so enrollment is proceeding as estimated. We will continue all through the year. We plan to complete enrollment next year. And so studies are proceeding according to plan.

因此招生工作正在按計劃進行。我們將全年繼續下去。我們計劃明年完成招生。研究正在按計劃進行。

To your question, we're borrowing a lot of learnings from GALACTIC and we believe we're in an advantaged situation for having conducted GALACTIC to know where to go for COMET, so that trial can enroll rapidly. We'll have more to say about that through the year.

對於您的問題，我們借鑒了 GALACTIC 的許多經驗，我們相信，透過進行 GALACTIC，我們處於有利地位，知道 COMET 應該如何開展，以便試驗能夠迅速開展。今年我們將會就此進行更多討論。

Thanks again.

再次感謝。

Thank you.

謝謝。

Mayank Mamtani, B. Riley Securities.

Mayank Mamtani，B. Riley 證券。

Good afternoon.

午安.

Good afternoon, team. Thanks for taking our questions and congrats on the progress. Just maybe switching gears to CK-586 HFpEF study. I think you mentioned the first two cohorts, low and mid dose level enrolling and completion by end of this year. Could you maybe just talk to the higher dose cohort is contingent on completion of the first two cohorts and maybe just what you're looking to learn on both the tolerability and obviously the biomarkers there in the HFpEF study? Thanks for taking our question.

大家下午好。感謝您回答我們的問題，並祝賀取得的進展。也許只是轉向 CK-586 HFpEF 研究。我想您提到了前兩個隊列，低劑量和中劑量水平的招募將在今年年底前完成。您能否談談，較高劑量組是否取決於前兩個組別的完成情況，以及您是否希望了解 HFpEF 研究中耐受性和生物標記的情況？感謝您回答我們的問題。

Maybe I'll ask Stuart to tackle that please.

也許我應該請史都華來解決這個問題。

Thank you. So the study is designed intentionally designed to be flexible. And so as you noted, our intent is to complete the first two cohorts by the end of the year and based on the information that we treat from those two cohorts then we would consider if we need to proceed with the third cohort or perhaps with a different dose. So it is a flexible design and that I think that really strengthens the study.

謝謝。因此，這項研究的設計是有意設計的，具有彈性。如您所說，我們的目標是在今年年底前完成前兩批治療，並根據這兩批治療的結果，考慮是否需要繼續進行第三批治療，或採用不同的劑量。所以這是一個靈活的設計，我認為這確實加強了研究。

With respect to the endpoints in the trial, first and foremost, we're evaluating safety and tolerability in this HFpEF population. We'll be collecting biomarker data, cardiac biomarkers, anti proBNP, as well as assessing pharmacokinetics and evaluating effects on ejection fraction. And so those are some of the key endpoints that we'll be evaluating to this is mainly a dose finding type of study. Thank you. Is there any other hopefully that answers your question?

關於試驗的終點，首先，我們正在評估 HFpEF 族群的安全性和耐受性。我們將收集生物標記數據、心臟生物標記、抗 proBNP，以及評估藥物動力學和評估對射血分數的影響。這些是我們將要評估的一些關鍵終點，這主要是劑量探索類型的研究。謝謝。還有其他可以回答您的問題的嗎？

Yes, it does. Thank you. Appreciate it.

是的。謝謝。非常感謝。

Thank you.

謝謝。

Yasmeen Rahimi, Piper Sandler

亞斯明·拉希米，派珀·桑德勒

Hello, Yasmeen.

你好，Yasmeen。

Hi, Robert. Thank you so much for all the great updates. I guess one of the questions that we were wondering about is recently the baseline demographics of the odyssey study was published. And I would love to maybe get Fady's thoughts on that study and what stood out to you. Just some commentary. I appreciate the commentary throughout the call that positive data from ODYSSEY, from MAPLE continue to grow the uptake of CMIs in this big market. I mean, we're talking about a million patients, which is a big mark, a high addressable population.

你好，羅伯特。非常感謝您提供的所有精彩更新。我想我們想知道的一個問題是最近公佈了奧德賽研究的基線人口統計。我很想了解 Fady 對這項研究的看法以及您認為最突出的一點。只是一些評論。我很欣賞整個通話過程中的評論，ODYSSEY 和 MAPLE 的積極數據繼續推動 CMI 在這個大市場的普及。我的意思是，我們談論的是一百萬患者，這是一個很大的數字，是一個很高的可尋址人群。

So if you could just kind of comment around that. I know, ACACIA is currently fully in enrollment mode but maybe is there any some differences that stand out to you as you look at that baseline population would be helpful. And I'll jump back in the queue.

所以如果你能就此發表一些評論的話。我知道，ACACIA 目前已全面進入招生模式，但當您查看基線人口時，也許存在一些對您來說突出的差異，這會有所幫助。我將重新回到隊列中。

Yes. Hi. I mean, I think the baseline characteristics were not unsurprising, and these are people that have significant symptoms. They have elevated biomarkers, reduced exercise capacity, all of those things that we expect to see in a population that is an HCM population. I think what is surprising is how similar they are to the oHCM patients with the exception of a gradient in the biomarker and other deficits that they have.

是的。你好。我的意思是，我認為基線特徵並不令人驚訝，這些人有明顯的症狀。他們的生物標記升高，運動能力下降，所有這些都是我們預計在 HCM 族群中會看到的現象。我認為令人驚訝的是，除了生物標記梯度和他們所具有的其他缺陷外，他們與 oHCM 患者有多相似。

So I think that it speaks to the fact that there are a lot of highly impacted patients with nHCM. We've seen both their trial enroll very well. We've seen our trial enroll very well. This is a condition that's probably not as uncommon as people originally thought. And I think the effectiveness of CMIs in them should -- will be elucidated by the results. But there's similarity in lots of ways to the oHCM patients, I think bode well for what we might expect to see.

所以我認為這表示有很多 nHCM 患者受到了嚴重影響。我們看到他們的試驗報名情況非常好。我們看到我們的試驗報名情況非常好。這種情況可能並不像人們最初想的那麼罕見。我認為 CMI 的有效性應該透過結果來闡明。但在很多方面與 oHCM 患者有相似之處，我認為這預示著我們可能看到的結果很好。

Thank you, Fady.

謝謝你，法迪。

Charles Duncan, Cantor Fitzgerald

查爾斯鄧肯、康托菲茨傑拉德

Hello, Charles.

你好，查爾斯。

Hey, good afternoon. Hey, Robert and team, congrats on a great year of progress. Lots of good questions asked, so I will send one in, in terms of biz dev. I'm just kind of wondering if you could characterize the kind of work that Sanofi did in terms of the China market. It seems like, obviously, it could be quite large. Wondering if you could provide any color on call it the unmet need there and how you might see it pace in terms of it being developed. And would you anticipate milestones yet this year in terms of cash payments or even early next year? Thanks.

嘿，下午好。嘿，羅伯特和他的團隊，祝賀你們取得了巨大的進步。提出了很多好問題，因此我將就業務開發方面提出一個問題。我只是想知道您是否可以描述一下賽諾菲在中國市場所做的工作。顯然，它看起來可能相當大。想知道您是否可以提供任何細節來說明它是否是尚未滿足的需求，以及您如何看待它的發展速度。您預計今年或明年年初在現金支付方面會取得里程碑式的進展嗎？謝謝。

Yes. So we've been very impressed by the degree to which Sanofi has jumped in and dialed up and stepped up in meaningful ways. I'll ask Isaac to comment on that and then Sung to speak to your second part of your question.

是的。因此，賽諾菲的參與和努力以及採取的有意義的行動令我們印象深刻。我將請艾薩克對此作出評論，然後請宋回答你問題的第二部分。

Sure. So as Robert said, we've been very impressed with Sanofi and their process. To be clear, this was a transaction that was done through CORXEL and Sanofi. But what we understand is there were multiple parties interested. There's a clear understanding of an unmet need in China. There are no REMS programs in China. So I think from that perspective, it went into Sanofi's value proposition of being able to go and take advantage of all the benefits of aficamten. And so they stepped into the collaboration.

當然。正如羅伯特所說，賽諾菲及其流程給我們留下了深刻的印象。需要明確的是，這是透過 CORXEL 和賽諾菲完成的交易。但據我們了解，有多方對此感興趣。人們清楚地認識到中國尚未滿足的需求。中國沒有REMS專案。因此，我認為從這個角度來看，它符合賽諾菲的價值主張，即能夠充分利用 aficamten 的所有優勢。於是他們開始了合作。

I can tell you that since then we have a very active dialogue with them as part of the potential approval this year. There are, as you know, milestones associated with approval, but again, they depend on that event happening in this calendar year. If not, they'll be pushed into 2026.

我可以告訴你，從那時起，作為今年可能批准的一部分，我們與他們進行了非常積極的對話。如您所知，批准過程中存在一些里程碑，但這些里程碑取決於該日曆年內發生的事件。如果不是，他們將被推遲到 2026 年。

Yes. And Charles, just expanding on the milestone question, we do expect meaningful milestones this year. And I would say these milestones, of course, we have multiple partners here, so I'm not going to be specific to a single partner, but these milestones are tied to clinical and regulatory milestones. So just to give you some color, we could be eligible up to $35 million in total across our partners.

是的。查爾斯，關於里程碑問題，我們確實期待今年取得有意義的里程碑。我想說這些里程碑，當然，我們在這裡有多個合作夥伴，所以我不會具體針對某個合作夥伴，但這些里程碑與臨床和監管里程碑有關。僅供大家參考，我們的合作夥伴總共可以獲得高達 3500 萬美元的資助。

And then as I mentioned, they've stepped up in some meaningful ways in terms of timelines, forecasts, manufacturing and supply requirements. Maybe I'll ask Andrew to comment on market sizing in China. Andrew, are you on mute?

正如我所提到的，他們在時間表、預測、製造和供應要求方面取得了一些有意義的進展。也許我會請安德魯評論中國的市場規模。安德魯，你靜音了嗎？

Yes, Charles. So in terms of population, China is also a concentrated market. There's around 400,000 diagnosed patients and there's a little over 1,000 hospitals where the vast majority over 80% of those patients are. There's likely a lot more patients in the rural and community settings that aren't diagnosed, so that could certainly pick up over time. The KOL universe is pretty small too, it's less than 500.

是的，查爾斯。所以從人口來看，中國也是一個集中的市場。確診患者約有 40 萬，而超過 80% 的患者就診於 1,000 多家醫院。在農村和社區環境中可能還有更多未被診斷的患者，因此隨著時間的推移，這一數字肯定會上升。KOL 的範圍也相當小，不到 500 個。

That's really the starting point for the market in China in terms of where it's going to take off. So certainly a high unmet need. And again, like a rare disease, this certainly is a concentrated market and a lot of available patients in China.

就中國市場即將起飛而言，這確實是個起點。因此，這肯定是一個很大的未滿足需求。再說一次，就像罕見疾病一樣，這肯定是一個集中的市場，在中國有很多患者。

I think the opportunity in China potentially could be under recognized and we would encourage equity research analysts to do their own work there, but we're very impressed by how Sanofi is embracing this opportunity. Operator?

我認為中國市場的機會可能被低估，我們鼓勵股票研究分析師在中國開展自己的工作，但賽諾菲如何抓住這個機會給我們留下了深刻的印象。操作員？

Jason Butler, Citizens JMP

Jason Butler，公民JMP

Hello, Jason.

你好，傑森。

Hi, Robert. Thanks for taking the question. You mentioned that the safety update submitted to FDA had additional data from FOREST-HCM. Can you talk to how much of that data in terms of patients or patient years is from after the protocol amendment was implemented to lower the frequency of echo monitoring?

你好，羅伯特。感謝您回答這個問題。您提到提交給 FDA 的安全性更新包含來自 FOREST-HCM 的附加資料。您能否談談，在實施協議修正案以降低超音波心動圖監測頻率之後，有多少患者數據或患者年份數據來自此？

And if you can make any comment as to whether the safety profile appears consistent before and after that protocol amendment was made? And then just lastly, are there any additional protocol amendments you're considering for forest in terms of echo monitoring? Thanks.

您能否評論一下在修改協議之前和之後的安全性概況是否一致？最後，在迴聲監測方面，您是否考慮對森林進行任何額外的協議修訂？謝謝。

Good questions. I'll turn to Fady, please.

好問題。請讓 Fady 發言。

Yes. Hi, Jason. I think the protocol amendment was put in place last year, but I would say that there isn't a lot of data yet that's accumulated from patients that have had every six-month monitoring echoes. That said, I'll remind you that we've literally thousands of six months -- about three-month monitoring echoes and you see very little impact of those either on dosing changes or patient safety. So as time goes on, probably this year, we'll see more six-month monitoring accumulate in those patients.

是的。你好，傑森。我認為該協議修正案是去年實施的，但我想說的是，目前還沒有從每六個月進行一次監測迴聲的患者身上累積大量數據。話雖如此，我要提醒您，我們實際上已經進行了數千次六個月至大約三個月的監測迴聲，並且您會發現這些迴聲對劑量變化或患者安全的影響非常小。因此，隨著時間的推移，可能在今年，我們將看到對這些患者進行更多的六個月監測。

At the moment, we don't have any other planned protocol amendments for forest. And, I don't think, I think the thing that I pointed out during my comments was that it seems to just, as we gain more data, the profile of aficamten doesn't seem to change and the safety that we've observed and presented on previously remains rather strong. We'll be updating those data with these new data cuts in the near future.

目前，我們還沒有計劃對森林協議進行任何其他修訂。而且，我不認為，我認為我在評論中指出的是，隨著我們獲得更多數據，aficamten 的概況似乎並沒有改變，而且我們之前觀察和呈現的安全性仍然相當強。我們將在不久的將來使用這些新的數據來更新這些數據。

And you'll see those data presented publicly. But to underscore what Fadi said, the good news is that whether it was ECHO monitored every three months or every six months, we believe strongly in aficamten, its safety and tolerability and we continue to see encouraging data that we think supports our expectation for a differentiated risk mitigation. Thank you, Jason.

你會看到這些數據被公開呈現。但要強調法迪所說的，好消息是，無論是每三個月還是每六個月監測一次 ECHO，我們都堅信阿菲卡姆滕、它的安全性和耐受性，而且我們繼續看到令人鼓舞的數據，我們認為這些數據支持我們對差異化風險緩解的預期。謝謝你，傑森。

Jason Zemansky, BofA

傑森‧澤曼斯基（Jason Zemansky），美國銀行

Hello, Jason.

你好，傑森。

Congrats on the progress. And appreciate you slipping us in. I was hoping to get some additional color on your comments regarding expansion into the first line setting. I was hoping you could speak to your strategy here, maybe if not to expand wholly into the community-based setting, but at least out of the centers of excellence where these patients are a lot more common. What are some of the challenges here getting prescribers on board who are maybe less comfortable administering a CMI? How dependent is it on the REMS itself and realistically you expect an uptake here?

恭喜你取得進展。感謝您讓我們加入。我希望能夠對您關於擴展到第一行設定的評論獲得一些額外的資訊。我希望您能在這裡談談您的策略，也許不是完全擴展到社區環境，但至少要擴展到這些患者更為常見的卓越中心之外。讓那些可能不太習慣管理 CMI 的開藥者加入進來面臨哪些挑戰？它對 REMS 本身的依賴程度如何？您實際上預期它會在這裡得到應用嗎？

Sure. So that's again a multi part question. We'll try to tackle it as best we can. I'll ask Andrew, caveated by underscoring that as relates to specific strategy, we probably won't elaborate in detail, but rather in a general term. Andrew?

當然。所以這又是一個由多部分組成的問題。我們將盡力解決這個問題。我會問安德魯，但需要強調的是，由於涉及具體策略，我們可能不會詳細闡述，而是用一個籠統的術語來表達。安德魯？

Yes. So first part of your question around first line setting, that's really not a concern in the near term. Generally, the way it goes is guidelines would get updated. The payers certainly and physicians certainly want to try beta blockers first. They're easy to use. They're relatively inexpensive wide access. But over time, you certainly may see first line treatment, and this will certainly provide the evidence.

是的。因此，您問題的第一部分涉及第一線設置，這在短期內確實不是一個問題。一般來說，指導方針會得到更新。付款人和醫生肯定想先嘗試β受體阻斷劑。它們很容易使用。它們價格相對便宜，使用範圍廣。但隨著時間的推移，你肯定會看到一線治療，這肯定會提供證據。

There are those that can't take beta blockers, those that have contraindications, those who can't tolerate, this provides the evidence that a CMI like aficamten is certainly if those studies positive, effective. There are those physicians, especially in the community in our market research that are maybe less educated and a bit apathetic around the prime of new therapy like a CMI, especially when you add on the monitoring requirements. This is a motivating factor for a segment of those physicians to recognize that a disease modifying therapy is a good kind of reason to believe and kind of get them on board.

有些人不能服用β受體阻斷劑，有些人有禁忌症，有些人不能耐受，這提供了證據，證明像阿菲卡姆滕這樣的 CMI 肯定是有效的，如果這些研究是積極的。有些醫生，尤其是在我們市場調查的社區中，可能受教育程度較低，對 CMI 等新療法的黃金時期有點冷漠，尤其是當你增加監測要求時。這是一個激勵因素，讓一部分醫生認識到，改變疾病的療法是值得相信並讓他們接受的好理由。

So I think the other thing is when you look at cardiovascular launches and launches in general, launches are generally linear for two to four years. We've looked at the last 8 to 10 cardiovascular launches. And then there's a high growth curve, Vehemently, it's because you're getting more prescribers on board, not just the KOLs, in this case, the specialized centers and academic centers.

所以我認為另一件事是，當你觀察心血管產品的發布和一般產品的發佈時，會發現產品發布通常在兩到四年內呈線性增長。我們研究了最近 8 到 10 次心血管發射。然後有一個高成長曲線，強烈地說，這是因為你獲得了更多的處方者，而不僅僅是 KOL，在這種情況下，是專門的中心和學術中心。

And once you can expand to beyond, say, 500 or 600 physicians who are the vast majority of the CMI market today around 80% to the thousands of cardiologists who currently know and treat this disease today, that's really where you'll see the market take off these patients and maintenance will start to go into the community, be maintained by a physician, they'll be attending congresses. So it's just the normal kind of growth and adoption curves that maybe is a little bit slowed by the monitoring requirement, but certainly maple for the reasons I stated should help.

一旦您可以將規模擴大到 500 或 600 名醫生以上，他們佔據了當今 CMI 市場的絕大多數，目前了解和治療這種疾病的數千名心臟病專家中約有 80% 是這樣的，您就會看到市場真正騰飛，這些患者和維護將開始進入社區，由醫生維護，他們將參加會議。因此，這只是正常的成長和採用曲線，可能會因監控要求而稍微減慢，但出於我所述的原因，maple 肯定會有所幫助。

Hopefully that answers your question.

希望這能回答你的問題。

Yes. Appreciate the color. Thanks.

是的。欣賞色彩。謝謝。

Thank you.

謝謝。

Thank you. And I am showing no further questions from our phone lines. I'd now like to turn the conference back over to Robert Blum, President and CEO, for any closing remarks.

謝謝。我沒有從我們的電話線中提出其他問題。現在，我想將會議交還給總裁兼執行長羅伯特布魯姆 (Robert Blum) 來做結束語。

Thank you, operator, and thank you to all the participants on our call today. We thank you for your continued support and your interest in Cytokinetics. We believe that 2024 was a very strong year for Cytokinetics and sets the table nicely for 2025, a year in which we hope to be delivering on the promise of our science and over 25 years of commitment to this area of biology now for the potential benefit of patients. We believe that we're executing very well on strategy, and we've outlined for you key milestones for this coming year. We look forward to keeping you abreast of our progress.

謝謝接線員，也感謝今天通話的所有參與者。我們感謝您對 Cytokinetics 的持續支持和關注。我們相信，2024 年對 Cytokinetics 來說是非常強勁的一年，並為 2025 年奠定了良好的基礎，我們希望在這一年兌現我們的科學承諾以及 25 年來對這一生物學領域的承諾，為患者帶來潛在的利益。我們相信我們的策略執行得很好，並且我們已經為您概述了來年的關鍵里程碑。我們期待讓您了解我們的進展。

And with that, operator, we can now conclude the call.

接線員，我們現在可以結束通話了。

Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect.

謝謝。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。