Zevra Therapeutics Inc (ZVRA) 2025 Q1 法說會逐字稿

Good afternoon and thank you for joining Zevra's first-quarter 2025 financial results and corporate update conference call. Today's call is being recorded and will be available via the Investor Relations section of the company's website later today. The host for today's call is Nichol Ochsner, Zevra's Vice President. Please go ahead.

下午好，感謝您參加 Zevra 2025 年第一季財務業績和公司更新電話會議。今天的電話會議正在錄音，並將於今天晚些時候透過公司網站的投資者關係部分提供。今天電話會議的主持人是 Zevra 副總裁 Nichol Ochsner。請繼續。

Thank you, and welcome to those who are joining us. Today, we will provide an overview of our recent accomplishments, followed by a review of first-quarter financial results. I encourage you to read our financial results news release, which was distributed this afternoon and is available in the Investor section of our website. Before we begin the call, please note that certain information shared today will include forward-looking statements.

謝謝大家，歡迎大家加入我們。今天，我們將概述我們最近的成就，然後回顧第一季的財務表現。我鼓勵您閱讀我們今天下午發布的財務業績新聞稿，您可以在我們網站的「投資者」部分找到。在我們開始通話之前，請注意，今天分享的某些資訊將包括前瞻性陳述。

Actual results may differ materially from those stated or implied by any forward-looking statements due to risks and uncertainties associated with Zevra's business. Forward-looking statements are not promises or guarantees and are inherently subject to risks, uncertainties, and other important factors that may lead to actual results differing materially from projections made.

由於與 Zevra 業務相關的風險和不確定性，實際結果可能與任何前瞻性陳述明示或暗示的結果有重大差異。前瞻性陳述並非承諾或保證，本質上受風險、不確定性和其他重要因素的影響，可能導致實際結果與預測有重大差異。

These forward-looking statements should be evaluated together with the cautionary statements contained in the risk factors section in our most recently quarterly report on Form 10-Q, annual report on Form 10-K, and our other filings with the SEC. I am pleased to welcome Zevra's management team members participating in today's call, Neil McFarlane, Zevra's President and Chief Executive Officer; LaDuane Clifton, our Chief Financial Officer; and Josh Schafer, our Chief Commercial Officer. Our Chief Medical Officer, Adrian Quartel, will also be available for today's question-and-answer session.

這些前瞻性陳述應與我們最近的 10-Q 表季度報告、10-K 表年度報告以及我們向美國證券交易委員會提交的其他文件中風險因素部分所包含的警示性陳述一起進行評估。我很高興歡迎 Zevra 管理團隊成員參加今天的電話會議，他們是 Zevra 總裁兼執行長 Neil McFarlane、財務長 LaDuane Clifton 和首席商務長 Josh Schafer。我們的首席醫療官 Adrian Quartel 也將出席今天的問答環節。

Now it's my pleasure to turn the call over to Neil.

現在我很高興將電話轉給尼爾。

Thank you, Nicole, and thank you for joining us this afternoon to review our strong progress and the ongoing execution of our four strategic pillars. Let me start with commercial excellence. We are delivering on our two commercial launches to bring innovative therapies to people living with rare diseases. We have exceeded our internal expectations for the MIPLYFFA launch and have enrolled over one-third of those diagnosed with Niemann-Pick disease type C, or NPC, in the United States.

謝謝你，妮可，也謝謝你今天下午加入我們，回顧我們取得的重大進展以及四大戰略支柱的持續執行。讓我先從商業卓越性說起。我們正在進行兩項商業發布，為患有罕見疾病的人提供創新療法。我們已經超越了對 MIPLYFFA 上市的內部預期，並在美國招募了超過三分之一的 C 型尼曼匹克病（NPC）患者。

With OLPRUVA for the treatment of certain urea cycle disorders, or UCDs, we refined our marketing efforts to further increase awareness and access for patients and providers. Moving on to pipeline and innovation, we are focused on where our capabilities have the greatest impact for patients as we progress our development programs.

透過 OLPRUVA 治療某些尿素循環障礙（UCD），我們改進了行銷力度，進一步提高患者和提供者的認知度和可及性。在管道和創新方面，隨著我們開發專案的推進，我們專注於我們的能力對患者產生最大影響的地方。

Our Phase 3 DISCOVER trial of Celiprolol, are late-stage assets for the potential treatment of Vascular Ehlers-Danlos syndrome, or VEDS, which has received both Orphan Drug and Breakthrough Therapy designations, continues to progress with patient enrollments. Additionally, we continue assessing value-enhancing strategic alternatives for our Phase 3 Ready asset, KP1077, for rare sleep disorders. These clinical-stage assets provide optionality and diversification to our portfolio.

我們對塞利洛爾進行的 III 期 DISCOVER 試驗是用於治療血管性埃勒斯-丹洛斯綜合徵（VEDS）的後期資產，該藥物已獲得孤兒藥和突破性療法認定，並且患者招募工作仍在繼續推進。此外，我們繼續評估針對罕見睡眠障礙的 3 期就緒資產 KP1077 的增值策略替代方案。這些臨床階段資產為我們的投資組合提供了選擇性和多樣化。

Turning to talent and culture, we have a passionate, highly motivated, experienced, and mission-driven team focused on our vision to bring life-changing therapies to people living with rare diseases. Our team's strong execution is being acknowledged. For example, we earned a spot on Fast Company's Top 10 Most Innovative Companies list in the medicines, therapeutics, and pharmaceuticals category.

談到人才和文化，我們擁有一支充滿熱情、積極進取、經驗豐富、以使命為導向的團隊，專注於我們的願景，為患有罕見疾病的人們帶來改變生活的治療方法。我們團隊的強大執行力正在被認可。例如，我們在《Fast Company》雜誌的醫藥、治療和製藥類別十大最具創新力公司榜單中佔有一席之地。

Finally, corporate foundation. This underpins all other pillars and allows us to responsibly invest in our long-term transformation through disciplined capital allocation while maintaining our position of financial strength. With the recent monetization of our pediatric rare disease Priority Review Voucher or PRV, we added $148.3 million of non-dilutive capital to our balance sheet, bolstering our financial strength. With this, we have ample resources and financial flexibility to execute on our strategic priorities independent from the capital markets.

最後，企業基礎。這是所有其他支柱的基礎，使我們能夠透過嚴格的資本配置負責任地投資於我們的長期轉型，同時保持我們的財務實力。隨著我們最近將兒科罕見疾病優先審查券或 PRV 貨幣化，我們在資產負債表中增加了 1.483 億美元的非稀釋性資本，增強了我們的財務實力。由此，我們擁有充足的資源和財務彈性，可以獨立於資本市場執行我們的策略重點。

Driving a little deeper into our commercial programs, we are pleased with the early success in the MIPLYFFA launch for the treatment of NPC, which is an ultra-rare neurodegenerative progressive and fatal disease. The launch is characterized by three unique patient cohorts: those who are participants of our Expanded Access Program, or EAP; those who are diagnosed and may or may not be receiving treatment; and finally, those who are undiagnosed and living with MPC for whom we seek to accelerate diagnosis and treatment.

深入研究我們的商業項目，我們對 MIPLYFFA 在治療 NPC 方面取得的早期成功感到高興，NPC 是一種極為罕見的神經退化性進行性疾病和致命疾病。此次發布的特點是針對三個獨特的患者群體：那些參與我們的擴展訪問計劃 (EAP) 的患者；那些已被診斷但可能正在接受或尚未接受治療的患者；最後，那些尚未被診斷但患有 MPC 的患者，我們尋求為他們加速診斷和治療。

We received a total of 122 prescription enrollment forms from launch through March 31, with 13 in the first quarter of 2025. Even in these early days of the launch, we have received prescription enrollment forms from all three patient cohorts, affirming the early impact of our commercial strategy.

從推出到 3 月 31 日，我們共收到 122 份處方登記表，其中 2025 年第一季收到 13 份。即使在推出初期，我們就已經收到了來自所有三個患者群體的處方登記表，這肯定了我們商業策略的早期影響。

Notably, as we have previously reported, all active US EAP participants have been enrolled to receive MIPLYFFA, and we have now closed the program, including locking the database and deactivating study centers ahead of our previously stated guidance. We are focused on providing MIPLYFFA to people living with NPC and have been educating prescribers and payers on the clinical benefit which demonstrates, in combination with migalastat, a halting of disease progression through 12 months of treatment.

值得注意的是，正如我們之前報導的那樣，所有活躍的美國 EAP 參與者都已報名參加 MIPLYFFA，而我們現在已經關閉了該計劃，包括鎖定資料庫並在我們之前發布的指導之前停用學習中心。我們專注於為患有 NPC 的人提供 MIPLYFFA，並一直在向處方者和付款人宣傳其臨床益處，該研究表明，與 migalastat 結合使用，可以透過 12 個月的治療阻止病情進展。

Beyond the pivotal trial, MIPLYFFA's safety profile and the long-term treatment effect have been evaluated in open-label extension studies and through our multi-center EAP with patients having as many as five to seven years of experience on treatment, which significantly differentiates MIPLYFFA and positions it as the cornerstone therapy. Josh will provide additional details related to our launch metrics later in today's call.

除了關鍵試驗之外，MIPLYFFA 的安全性和長期治療效果已在開放標籤擴展研究中得到評估，並透過我們的多中心 EAP 對擁有多達五至七年治療經驗的患者進行了評估，這顯著地區別於 MIPLYFFA 並將其定位為基石療法。喬希將在今天稍後的電話會議中提供與我們的發布指標相關的更多詳細資訊。

Beyond the successful US launch, our goal is to provide access to as many people living with NPC as possible by expanding the availability of MIPLYFFA outside of the US. We are diligently working towards expanding our regulatory submissions with an immediate focus on a Marketing Authorization Application or MAA in Europe in the second half of this year, where we estimate approximately 1,100 people are living with MPC.

除了在美國成功推出之外，我們的目標是透過擴大 MIPLYFFA 在美國以外的應用範圍，讓盡可能多的 NPC 患者能夠使用該藥物。我們正在努力擴大我們的監管提交範圍，並立即關註今年下半年在歐洲的營銷授權申請或 MAA，我們估計歐洲約有 1,100 人患有 MPC。

As a reminder, the European market is already well established, with access to a marketed treatment for more than a decade. Further, we're expanding our global EAP, which has recently increased to approximately 85 NPC patients compared to the previously reported 70 to 80 patients. Our continued investment in MIPLYFFA's global EAP in combination with a more established market could accelerate commercialization upon approval in Europe.

需要提醒的是，歐洲市場已經很成熟，並且已有十多年的市場銷售治療經驗。此外，我們正在擴大全球 EAP，最近已將 NPC 患者人數從先前報告的 70 至 80 名增加到約 85 名。我們對 MIPLYFFA 全球 EAP 的持續投資，加上更成熟的市場，可以加速其在歐洲獲得批准後的商業化進程。

Turning to OLPRUVA. From initial product availability in July of 2023, and including Zevra's promotion of OLPRUVA in late January of 2024, through the end of the first quarter, 2025, we've received a total of 28 prescription enrollment forms, with five prescription enrollment forms during the first quarter of this year. In November, we outlined a plan to refine our commercial strategy towards the adult and OTC-deficient populations for whom OLPRUVA's portability and ease of administration may provide the greatest benefit.

轉向 OLPRUVA。從 2023 年 7 月產品首次上市，包括 Zevra 於 2024 年 1 月下旬推廣 OLPRUVA，到 2025 年第一季末，我們共收到 28 份處方登記表，其中今年第一季收到 5 份處方登記表。11 月，我們制定了一項計劃，旨在完善我們的商業策略，面向成人和 OTC 缺乏人群，OLPRUVA 的便攜性和易於管理性可能為他們帶來最大的益處。

The enrollments received in the first quarter were all within this patient segment, suggesting early signs that this strategy is gaining traction. Before turning the call over to Josh, I'll share a few more updates on our clinical stage assets. Through our Phase 3 DISCOVER trial, celiprolol is being evaluated as a potential treatment of VEDS, a devastating connective tissue disorder caused by the COL3A1 gene mutation and characterized by spontaneous arterial aneurysms, hollow organ ruptures, and aortic dissections.

第一季收到的註冊患者全部屬於這一患者群體，這表明該策略正在獲得關注。在將電話轉給喬希之前，我將分享一些關於我們臨床階段資產的最新消息。透過我們的 3 期 DISCOVER 試驗，塞利洛爾正在被評估為 VEDS 的潛在治療方法，VEDS 是一種由 COL3A1 基因突變引起的破壞性結締組織疾病，其特徵是自發性動脈瘤、空腔器官破裂和主動脈夾層。

In the US, approximately 7,500 people are living with VEDS, where the standard of care relies on reactive and invasive surgical interventions with no approved treatments. Celiprolol is also currently used off label as a standard of care for VEDS in certain European countries. During the first quarter, we enrolled five additional subjects in the DISCOVER trial, bringing the total to 32. This is an event-driven trial, and the rate of enrollment is important, and we're implementing various strategies, including increasing our efforts to focus on providers and clinics specializing in genetically confirmed COL3A1-positive patients.

在美國，大約有 7,500 人患有 VEDS，其護理標準依賴反應性和侵入性手術幹預，而沒有核准的治療方法。目前，在某些歐洲國家，塞利洛爾也被用作 VEDS 的標準治療方法。在第一季度，我們又在 DISCOVER 試驗中招募了 5 名受試者，使總數達到 32 名。這是一項事件驅動的試驗，入組率很重要，我們正在實施各種策略，包括加強關注專門治療基因確診的 COL3A1 陽性患者的提供者和診所。

During the first quarter, we began receiving leads from a recently initiated genetic testing program, providing our team with a new group of confirmed VEDS patients for outreach. Importantly, we are optimistic in this strategy to drive enrollment and expect to see an increase in the enrollment rate in the upcoming quarters.

在第一季度，我們開始收到來自最近啟動的基因檢測計劃的線索，為我們的團隊提供了一組新的確診 VEDS 患者以供外展。重要的是，我們對這項推動入學的策略持樂觀態度，並預計未來幾季入學率將會上升。

There are also several updates related to the review of our extensive IP portfolio as we seek to extract value by determining where we continue to invest as well as where we choose to stop investing based on our strategic plan. I'm pleased to report that earlier this month, we've outlicensed intellectual property related to a pre-clinical prodrug, an undisclosed party for a nominal upfront payment, potential future milestones, and mid-single-digit royalties on net sales. We will continue to optimize and curate our IP portfolio through a variety of avenues to realize value for the company and our shareholders.

我們力求透過根據策略計畫確定繼續投資的地方以及選擇停止投資的地方來獲取價值，同時也對我們廣泛的智慧財產權組合的審查進行了多項更新。我很高興地報告，本月早些時候，我們已將與臨床前藥物相關的知識產權授權給未公開的一方，並向其支付了象徵性的預付款、潛在的未來里程碑以及淨銷售額的中等個位數特許權使用費。我們將繼續透過各種途徑優化和管理我們的知識產權組合，為公司和股東實現價值。

Additionally, regarding Apadaz, which was previously approved for the treatment of pain and has not been commercially available since 2023, we have made a strategic decision to formally withdraw the NDA. By eliminating the regulatory activities associated with maintaining approval, we are further reducing costs. We are continuing Zevra's transformation into a patient-centric, commercial-stage rare disease therapeutics company.

此外，對於先前核准用於治療疼痛但自2023年起尚未上市的Apadaz，我們已做出策略決策，正式撤回NDA。透過消除與維持批准相關的監管活動，我們進一步降低了成本。我們正在繼續推動 Zevra 轉型為一家以患者為中心、商業階段的罕見疾病治療公司。

With our bolstered cash balance, we are well-positioned to support our stated strategic priorities and execute on our long-term vision for the company by establishing MIPLYFFA as a cornerstone treatment for NPP globally, maximizing our commercial opportunity with OLPRUVA, and supporting our growth through our development pipeline, including the ongoing Phase 3 trial for celiprolol. We continue to build on our track record of execution, positioning us to make future investments that are in alignment with our strategic plan.

憑藉增強的現金餘額，我們完全有能力支持既定的策略重點，並實現公司的長期願景，將 MIPLYFFA 確立為全球 NPP 的基石治療方法，最大限度地利用 OLPRUVA 的商業機會，並透過我們的開發管道支持我們的成長，包括正在進行的塞利洛爾 3 期試驗。我們將繼續鞏固我們的執行記錄，使我們能夠進行符合我們策略計畫的未來投資。

Let me turn the call over to Josh, who will give an update on our commercial products.

讓我把電話轉給喬希，他將介紹我們的商業產品的最新情況。

Thank you, Neil, and good afternoon. Today, while discussing our commercial products, we will provide the following metrics, prescription enrollment forms for the quarter, the percent of covered lives, and net revenue. Beginning with MIPLYFFA, As Neil stated, the launch is progressing well and exceeding our expectations. With our EAP cohort fully enrolled, we are focused on reaching the diagnosed and undiagnosed cohorts.

謝謝你，尼爾，下午好。今天，在討論我們的商業產品時，我們將提供以下指標、本季的處方登記表、受保人次百分比和淨收入。從 MIPLYFFA 開始，正如 Neil 所說，發布進展順利，超出了我們的預期。隨著我們的 EAP 隊列完全入學，我們專注於接觸已確診和未確診的隊列。

We have seen steady growth in the first quarter with 13 prescription enrollment forms, all representing individuals new to MIPLYFFA, which indicates a broadening of both the patient and prescriber base. This is a result of our ongoing efforts to raise awareness of NPC and to educate prescribers about MIPLYFFA's clinically differentiated profile.

我們在第一季看到了穩定成長，共有 13 份處方登記表，均來自 MIPLYFFA 的新用戶，這表明患者和處方者群體都在擴大。這是我們不斷努力提高人們對 NPC 的認識並讓處方者了解 MIPLYFFA 的臨床差異化特徵的結果。

We estimate that there are approximately 900 people living with NPC in the US, of which only 300 to 350 have been diagnosed. Since launch through March 31, we have received a total of 122 prescription enrollment forms, meaning that roughly one-third of the estimated individuals diagnosed with NPC in the US have been enrolled to receive MIPLYFFA. As a reminder, a prescription enrollment form is a prescription submitted to our specialty pharmacy, initiating the benefits investigation process to determine reimbursement and can lead to a 30-day paid dispense of MIPLYFFA.

我們估計，美國大約有 900 人患有鼻咽癌，其中只有 300 至 350 人被診斷出來。自推出以來至 3 月 31 日，我們共收到 122 份處方登記表，這意味著美國大約三分之一的 NPC 確診患者已登記接受 MIPLYFFA 治療。提醒一下，處方登記表是提交給我們專科藥房的處方，用於啟動福利調查流程以確定報銷，並可獲得 30 天的 MIPLYFFA 付費配藥。

Regarding market access, many payers have not yet formalized their formulary coverage or reimbursement policies, and our team has been actively engaging with payers to secure reimbursement. Through the end of the first quarter, we have achieved 38% of covered lives, which is in line with our expectations at this stage of launch.

關於市場准入，許多付款人尚未正式確定其處方集覆蓋範圍或報銷政策，我們的團隊一直在積極與付款人合作以確保報銷。截至第一季末，我們的覆蓋率已達 38%，這符合我們在此階段推出的預期。

We have been able to secure reimbursement authorization for many of our patients through direct formulary coverage or via the medical exception process. While initial denials are commonplace among rare disease products, we are very pleased with our team's ability to swiftly address payer challenges by presenting MIPLYFFA's robust and differentiated clinical data.

我們已經能夠透過直接處方集覆蓋或醫療例外流程為許多患者獲得報銷授權。雖然罕見疾病產品最初被拒絕的情況很常見，但我們很高興我們的團隊能夠透過提供 MIPLYFFA 強大且差異化的臨床數據來迅速應對付款人的挑戰。

NPC is a lysosomal storage disorder that is caused by progressive lipid buildup leading to cell death and ultimately organ dysfunction in the spleen, liver, and brain. The difficulty in diagnosing NPC patients centers around variability in age of disease onset and the heterogeneity of symptoms. As a result, the disease progression is measured by the only clinically validated tool, the four-domain NPC Clinical Severity Scale, which evaluates four key domains deemed by NPC experts to be the most important, including ambulation, fine motor skills, speech, and importantly, swallow abilities.

NPC 是一種溶小體貯積症，由進行性脂質積聚引起，導致細胞死亡，最終導致脾臟、肝臟和大腦的器官功能障礙。鼻咽癌患者診斷的困難主要在於發病年齡的多變性和症狀的異質性。因此，疾病進展由唯一經過臨床驗證的工具——四領域 NPC 臨床嚴重程度量表來衡量，該量表評估 NPC 專家認為最重要的四個關鍵領域，包括行走、精細運動技能、語言以及重要的吞嚥能力。

MIPLYFFA is the only product approved by the FDA based on the NPC Clinical Severity Scale. And the data in our label demonstrate that MIPLYFFA, in combination with migalastat, halts disease progression through 12 months of treatment, as shown by a greater than 2-point improvement in patients receiving MIPLYFFA and migalastat compared to those receiving migalastat alone. It is important to note that only a 1-point improvement is needed to demonstrate a clinically meaningful difference with a well-tolerated safety profile.

MIPLYFFA 是唯一根據 NPC 臨床嚴重程度量表獲得 FDA 核准的產品。我們標籤中的數據表明，MIPLYFFA 與米加拉司他聯合使用，經過 12 個月的治療可以阻止病情進展，接受 MIPLYFFA 和米加拉司他聯合治療的患者與單獨接受米加拉司他治療的患者相比，病情改善超過 2 個百分點。值得注意的是，僅需 1 點的改善即可證明具有良好耐受性的安全性和臨床上有意義的差異。

Additionally, MIPLYFFA is the only FDA-approved product for NPC with more than five years of clinical data in its label and with more than 270 NPC patients who have participated in our pivotal trial, our open-label extension study, or our EAP. In our view, these data, in addition to its well-tolerated safety profile, establishes MIPLYFFA as the cornerstone of therapy for NPC.

此外，MIPLYFFA 是唯一獲得 FDA 批准的 NPC 產品，其標籤上有超過五年的臨床數據，並且有超過 270 名 NPC 患者參與了我們的關鍵試驗、開放標籤擴展研究或 EAP。我們認為，這些數據以及其良好的耐受性安全性使 MIPLYFFA 成為 NPC 治療的基石。

Building on our strong body of evidence, we recently issued a publication discussing mechanistic insights into MIPLYFFA's mediated effects on lysosome function in NPC in the Journal of Molecular Genetics and Metabolism. The elucidation of MIPLYFFA's differentiated mechanism of action marks a critical step in understanding its interactions with NPC at a cellular level. These insights substantiate how MIPLYFFA addresses the underlying pathology of NPC and supports the long-term benefit observed in our clinical trials.

基於我們強有力的證據，我們最近在《分子遺傳學和代謝雜誌》上發表了一篇出版物，討論了 MIPLYFFA 對 NPC 溶酶體功能介導影響的機制見解。MIPLYFFA 差異化作用機制的闡明標誌著在細胞層面上理解其與 NPC 相互作用的關鍵一步。這些見解證實了 MIPLYFFA 如何解決 NPC 的潛在病理學並支持我們在臨床試驗中觀察到的長期益處。

During our fourth-quarter call, we unveiled numerous initiatives to reach the NPC patient cohorts namely those who are diagnosed and may or may not be receiving treatment, as well as the undiagnosed population. We continue to analyze claims data to identify existing patients, and we are employing targeting techniques to identify new and undiagnosed patients based on related symptoms and conditions.

在第四季度電話會議上，我們公佈了多項舉措，以涵蓋鼻咽癌患者群體，即那些已確診但可能正在接受或可能未接受治療的患者，以及未確診的人群。我們繼續分析索賠數據以識別現有患者，並且我們正在採用定位技術根據相關症狀和狀況識別新的和未確診的患者。

In addition, our targeted media campaign to build awareness and educate about early signs and symptoms of NPC is proving to be successful. We have expanded to a national scale reaching households across the US. Our team is amplifying the reach of these new segments through branded geo-targeting efforts in the corresponding regions. And these new segments are increasing awareness of NPC and the availability of treatment options and are primarily designed to resonate with individuals who have been diagnosed but are not yet receiving treatment.

此外，我們為提高公眾意識和普及鼻咽癌早期症狀而進行的有針對性的媒體宣傳活動已被證明是成功的。我們的業務已擴展到全國範圍，覆蓋美國各地的家庭。我們的團隊正在透過在相應地區進行品牌地理定位工作來擴大這些新細分市場的覆蓋範圍。這些新的部分正在提高人們對鼻咽癌和治療方案可用性的認識，主要是為了引起那些已被診斷但尚未接受治療的個人的共鳴。

We also launched our disease state awareness campaign, Learn NPC, Read Between the Signs, on Rare Disease Day this past February, and it's driving disease recognition and early diagnosis. Treatment of NPC is multifaceted, and our program provides education and genetic testing options for individuals with suspected lysosomal storage disorders.

我們還在今年二月的罕見疾病日發起了疾病狀態意識活動“了解 NPC，讀懂體徵”，以推動疾病識別和早期診斷。NPC 的治療是多方面的，我們的計畫為疑似患有溶小體貯積症的個人提供教育和基因檢測選項。

We have already seen the impact of this initiative with new patients who were not previously diagnosed with NPC being identified, enabling us to facilitate earlier diagnosis and offer MIPLYFFA as a treatment option. In summary, we are encouraged by the early results of our efforts to engage the diverse patient cohorts and we're looking forward to sharing our ongoing progress and future success with the program.

我們已經看到了這項措施的影響，一些先前未被診斷出患有鼻咽癌的新患者得以識別，這使我們能夠促進早期診斷並提供 MIPLYFFA 作為治療選擇。總而言之，我們對吸引不同患者群體的努力所取得的早期成果感到鼓舞，我們期待與該計劃分享我們正在進行的進展和未來的成功。

Now let's turn to OLPRUVA, our commercial product for the treatment of certain UCDs. UCDs are a group of rare inherited metabolic disorders resulting from a defect in one of the six enzymes, or two transporters, in the urea cycle, causing an accumulation of ammonia, known as hyperammonemia, which can be toxic and lead to neurocognitive damage or even death.

現在讓我們來談談 OLPRUVA，這是我們用於治療某些 UCD 的商業產品。UCD 是一組罕見的遺傳性代謝紊亂，由尿素循環中的六種酶或兩種轉運蛋白中的一種缺陷引起，導致氨的積累，稱為高氨血症，這種疾病可能具有毒性並導致神經認知損傷甚至死亡。

As we have discussed in prior quarters, we have moderated our expectations for the pace of the launch, given the unique dynamics of the UCD commercial landscape. From initial product availability in July of 2023, and including Zevra's promotion of OLPRUVA from January 2024 through the end of this first quarter, 28 total prescription enrollment forms for OLPRUVA have been received, including five in this first quarter of 2025. In the case of OLPRUVA, our prescription enrollment forms may also include our 30-day free trial program.

正如我們在前幾個季度所討論的那樣，考慮到 UCD 商業格局的獨特動態，我們已經降低了對發布速度的預期。從 2023 年 7 月產品首次上市，包括 Zevra 從 2024 年 1 月到今年第一季末對 OLPRUVA 的推廣，共收到 28 份 OLPRUVA 處方登記表，其中 2025 年第一季收到 5 份。就 OLPRUVA 而言，我們的處方登記表可能還包括 30 天免費試用計劃。

As Neil highlighted, we have refined our marketing strategy to more specifically target the adult patient seeking more independence as well as the OTC-deficient and carrier population who may receive greater benefit from the portability and palatability offered by OLPRUVA while encountering fewer reimbursement obstacles.

正如 Neil 所強調的，我們已經改進了行銷策略，更具體地針對尋求更多獨立性的成年患者以及 OTC 缺乏和攜帶者人群，他們可以從 OLPRUVA 提供的便攜性和適口性中獲得更大的好處，同時遇到更少的報銷障礙。

All enrollment forms in the first quarter align with our targeted patient segment, suggesting that this positioning resonates with prescribers. Given that patients with this disease typically only see their physician one to two times a year, we anticipate that the impact of our refined marketing strategy will require additional quarters to gain further traction.

第一季的所有登記表都與我們的目標患者群體一致，這表明這種定位與處方者產生了共鳴。鑑於患有這種疾病的患者通常每年只看醫生一到兩次，我們預計我們改進的營銷策略的影響將需要額外的幾個季度才能獲得進一步的牽引力。

For both our commercial products, we remain committed to patient access and focus on delivering comprehensive patient services through our in-house program, Amplify Assist. Our field case managers who support both MIPLYFFA and OLPRUVA are demonstrating early impact through their ability to assist with reimbursement hurdles.

對於我們的兩種商業產品，我們始終致力於患者訪問，並專注於透過我們的內部計劃 Amplify Assist 提供全面的患者服務。我們支援 MIPLYFFA 和 OLPRUVA 的現場案例經理透過協助解決報銷障礙的能力展示了早期影響。

And currently, our market access team continues to engage with payers to identify opportunities for OLPRUVA to improve its formulary position. We maintain regular communication with payers and have increased covered lives to 78%. I look forward to sharing additional updates in the coming quarters.

目前，我們的市場准入團隊繼續與付款人合作，尋找 OLPRUVA 改善其處方地位的機會。我們與付款人保持定期溝通，並將受保人數提高到 78%。我期待在接下來的幾個季度分享更多更新。

I will now pass the call to LaDuane, who will present the financial results for the first quarter of 2025.

現在我將把電話轉給拉杜安，他將介紹 2025 年第一季的財務表現。

Thank you, Josh. And good afternoon, everyone. In addition to the financial details included in today's call, we encourage you to refer to Zevra's quarterly report on Form 10-Q for more detailed information which we intend to file shortly. In the first quarter of 2025, we reported net revenue of $20.4 million, comprised of $17.1 million from MIPLYFFA revenue, $0.1 million from OLPRUVA revenue, $2.3 million in net reimbursements from the French EAP for arimoclomol, and $0.9 million from royalties and other reimbursements under the Astaris license.

謝謝你，喬希。大家下午好。除了今天電話會議中包含的財務細節外，我們還鼓勵您參考 Zevra 的 10-Q 表季度報告，以獲取我們打算很快提交的更多詳細資訊。2025 年第一季度，我們報告的淨收入為 2040 萬美元，其中包括 MIPLYFFA 收入 1710 萬美元、OLPRUVA 收入 10 萬美元、來自法國 EAP 的 arimoclomol 淨報銷 230 萬美元，以及 Astaris 許可下的特許權使用費和其他 90 萬美元報銷。

For our commercial products, MIPLYFFA and OLPRUVA, we recognize revenue when shipments are received by the specialty pharmacy. Our operating expense for the first quarter was $22.8 million, which was a decrease of [$0.6 million] compared to the same quarter a year ago. R&D expenses were [$3.3 million] for Q1 2025, which was a decrease of [$9 million] compared to Q1 2024 due primarily to a decrease in third-party costs upon completion of the KP1077 Phase 2 trial combined with a decrease in personnel-related costs.

對於我們的商業產品 MIPLYFFA 和 OLPRUVA，我們在專科藥房收到貨物時確認收入。我們第一季的營運費用為 2,280 萬美元，與去年同期相比減少了 60 萬美元。2025 年第一季的研發費用為 [330 萬美元]，與 2024 年第一季相比減少了 [900 萬美元]，主要原因是 KP1077 第 2 階段試驗完成後第三方成本減少，同時人員相關成本減少。

SG&A expenses were $19.5 million for Q1 2025, which was an increase of $9.6 million. Period-over-period increase in SG&A expenses was primarily related to an increase in personnel-related costs, professional fees, and other expenses associated with our commercial, medical, and launch activities. Net loss for the first quarter of 2025 was $3.1 million or $0.06 per basic and diluted share, compared to $16.6 million or $0.40 per basic and diluted share for the same quarter a year ago.

2025 年第一季的銷售、一般及行政費用為 1,950 萬美元，較上年同期增加 960 萬美元。銷售、一般及行政費用的增加主要與人員相關成本、專業費用以及與我們的商業、醫療和發布活動相關的其他費用的增加有關。2025 年第一季淨虧損為 310 萬美元，即每股基本虧損和稀釋虧損均為 0.06 美元，而去年同期淨虧損為 1,660 萬美元，即每股基本虧損和稀釋虧損均為 0.40 美元。

As of March 31, 2025, total cash, cash equivalents, and investments were $68.7 million which was a decrease of [$6.8 million] compared to December 31, 2024. Combined with the net proceeds of $148.3 million from the sale of the PRV received just after the end of the quarter on April 1, cash, cash equivalents, and investments would be $217 million. Total debt was approximately [$60 million].

截至 2025 年 3 月 31 日，現金、現金等價物及投資總額為 6,870 萬美元，與 2024 年 12 月 31 日相比減少了 [680 萬美元]。加上 4 月 1 日本季結束後出售 PRV 所獲得的 1.483 億美元淨收益，現金、現金等價物和投資將達到 2.17 億美元。總債務約為[6000萬美元]。

As mentioned earlier, adding the non-dilutive capital from the PRV sale has further enhanced our financial flexibility to support our strategic priorities, which includes executing on the commercial launches of MIPLYFFA and OLPRUVA, and supporting our ongoing Phase 3 trial for celiprolol.

如前所述，增加 PRV 銷售中的非稀釋性資本進一步增強了我們的財務靈活性，以支持我們的戰略重點，包括執行 MIPLYFFA 和 OLPRUVA 的商業發布，以及支持我們正在進行的塞利洛爾 3 期試驗。

We currently have ample resources to execute on our strategic priorities independent from the capital markets. Our financial results for Q1 2025 reflect the solid momentum in building a leading rare disease therapeutics company, and we are pleased with the opportunities we have in 2025 and beyond to drive value creation through disciplined investments where we can win.

我們目前擁有充足的資源來獨立於資本市場執行我們的策略重點。我們 2025 年第一季的財務表現反映了我們打造領先罕見疾病治療公司的強勁勢頭，我們對 2025 年及以後的機會感到高興，我們將透過有紀律的投資來推動價值創造，從而贏得勝利。

Now I'll turn the call back to Neil for his closing remarks.

現在我將把電話轉回給尼爾，請他作最後發言。

2025 is off to a terrific start for Zevra. The launch of MIPLYFFA is exceeding expectations, our course corrections and marketing strategy for OLPRUVA are gaining traction, and we're advancing our development pipeline. Today, driven by our sustained execution, we believe we're well positioned for future growth and see Zevra as a promising commercial-stage rare disease therapeutics company with a clear plan to drive shareholder value. Our vision for the future is bright, and we have many opportunities to serve the needs of patients and caregivers as we execute on our mission.

2025 年對 Zevra 來說是一個美好的開始。MIPLYFFA 的推出超出了預期，我們對 OLPRUVA 的路線修正和行銷策略正在獲得關注，我們正在推進我們的開發管道。今天，在我們持續執行的推動下，我們相信我們已為未來的成長做好了準備，並將 Zevra 視為一家有前途的商業階段罕見病治療公司，擁有明確的計劃來提升股東價值。我們對未來的願景是光明的，在執行我們的使命時，我們有很多機會滿足病人和照護人員的需求。

Thank you for joining the call, and we'll now open the call for questions. Operator?

感謝您參加電話會議，我們現在開始提問。操作員？

(Operator Instructions) Sumant Kulkarni at Canaccord.

（操作員指示）Canaccord 的 Sumant Kulkarni。

Good afternoon. It's nice to see the progress, and thanks for taking our questions. I have a couple. So first, relative to the 122 patient enrollment forms, could you give us any details on the number of patients that are actually on MIPLYFFA right now and what the spread of reimbursed patients might be?

午安.很高興看到進展，並感謝您回答我們的問題。我有一對。那麼首先，相較於 122 份病患登記表，您能否向我們提供有關目前實際接受 MIPLYFFA 治療的病患人數以及報銷病患分佈的詳細資訊？

Thanks, Sumant. And just before I answer that question, I want to let everybody know that we're taking the call from multiple locations, so it may necessitate a slight delay in responding as we get the folks who are going to be answering the question. I'll hand that question directly off to Josh in regards to the strong performance we've seen with MIPLYFFA so far.

謝謝，蘇曼特。在我回答這個問題之前，我想讓大家知道，我們正在從多個地方接聽電話，因此在我們聯繫將要回答這個問題的人時，可能需要稍微延遲回复。關於我們迄今為止看到的 MIPLYFFA 的強勁表​​現，我將直接把這個問題交給 Josh。

Thanks, Sumant. So as noted, we have seen 122 or received 122 enrollments since the launch through the end of the first quarter. We do not report on how many of those are actively on drug, but I can say that the majority of them are on drug, and those who are not yet are going through a process of benefits investigation and are in some stage of pending. Some might be receiving what we call Quick Start, which is free drug while we investigate the benefits and then intend to convert those patients to paid. And then there may be others that are just in some various stage of benefits investigation.

謝謝，蘇曼特。正如所指出的，自推出到第一季末，我們已經看到或收到了 122 份報名。我們沒有報告其中有多少人正在積極吸毒，但我可以說，他們中的大多數人都在吸毒，而那些還沒有吸毒的人正在經歷福利調查過程，並處於待決階段。有些人可能會獲得我們所謂的「快速啟動」服務，即免費藥物，同時我們會調查其益處，然後打算將這些患者轉為付費患者。可能還有其他人正處於福利調查的不同階段。

Got it. And one more before I hop into the queue. You mentioned denials of reimbursement at early stages in rare disease launches are to be expected. That's understandable, but could you give us any sense of what the top reason might be for the denial of MIPLYFFAw?

知道了。在我排隊之前，我還要再說一句話。您提到，在罕見疾病藥物研發初期拒絕報銷是意料之中的事。這是可以理解的，但是您能否告訴我們拒絕 MIPLYFFAw 的主要原因是什麼？

Absolutely, and those are two different data points. The 38% of covered lives is looking at the total number of patients out there, excuse me, the total number of people out there with insurance. 38% of those total covered lives who are receiving commercial insurance, federal insurance, VA, are covered currently. And then any challenges that we're finding right now, we haven't seen some initial denials, and that's totally to be expected with the rare disease product.

絕對如此，這是兩個不同的數據點。38% 的受保人數指的是所有病人，不好意思，是指所有有保險的人數。目前，接受商業保險、聯邦保險和退伍軍人事務部保險的總受保人數中有 38% 得到了保險。對於我們目前遇到的任何挑戰，我們還沒有看到一些最初的否認，這對於罕見疾病產品來說是完全可以預料到的。

And that is typical of products that have to go through some sort of prior authorization before they can get approved. We've been able to get coverage for almost all of our patients, either through direct formulary -- either direct formulary status or through some sort of medical exception process, which might require a physician writing a letter of medical necessity, but we've had great success in getting that covered.

這對於必須經過某種事先授權才能獲得批准的產品來說是很典型的。我們已經能夠為幾乎所有患者提供保險，要么通過直接處方集 - 要么通過直接處方集狀態，要么通過某種醫療例外程序，這可能需要醫生寫一份醫療必要性證明，但我們在獲得保險方面取得了巨大的成功。

And it's largely due to the demonstrated differentiation that MIPLYFFA has, with it being the only drug that's demonstrated the halting of disease progression through 12 months. It's got five to seven years of patient experience with more than 270 patients treated. And we have the only clinically validated endpoint for NPC, which is the Niemann-Pick clinical severity scale.

這很大程度上歸功於 MIPLYFFA 所展現出的差異化，它是唯一被證明能夠在 12 個月內阻止病情進展的藥物。該醫院擁有五至七年的病患治療經驗，已治療超過 270 名病患。我們擁有唯一經過臨床驗證的 NPC 終點指標，即尼曼-匹克臨床嚴重程度量表。

Thank you.

謝謝。

Yes. Sumant, maybe I'll just bring to the forefront. Josh laid it out beautifully. Our differentiation in the clinical profile is what's really driving the strong performance. The feedback from physicians and so far how we've been able to address the market access challenges that come up with every product that's in the specialty space is really demonstrating the strength of the data. That's really what's driving a lot of our performance today. Thanks.

是的。蘇曼特，也許我只會把它帶到最前面。喬希把它佈置得很漂亮。我們在臨床表現上的差異化才是真正推動強勁表現的因素。來自醫生的回饋以及迄今為止我們如何應對專業領域中每種產品所面臨的市場准入挑戰確實證明了數據的實力。這確實是我們今天表現的動力。謝謝。

(Operator Instructions) Jason Butler, Citizens.

（操作員指示）傑森·巴特勒，公民。

Hi, thanks for taking the questions and congrats on the quarter. A couple for me on MIPLYFFA. First of all, how much visibility do you have into whether patients are coming from that undiagnosed bucket versus diagnosed but not on a therapy right now? And just how should we think about bringing those patients on board, the cadence you can bring those patients on board throughout the year. And then second question, just qualitatively, can you speak to how inventory levels end of the quarter versus the end of 2024? Thank you.

嗨，感謝您回答問題並祝賀本季取得佳績。我在 MIPLYFFA 上見過幾對。首先，您能多大程度上了解患者是來自未確診患者群體，還是來自已確診但尚未接受治療的患者群體？我們應該如何考慮讓這些患者加入我們，全年以什麼樣的節奏讓這些患者加入我們。然後第二個問題，從品質上講，您能否談談本季末與 2024 年底的庫存水準如何？謝謝。

So Jason, thanks for the question. I'll try to quarterback this a little bit. I'll ask Josh to talk a little bit specifically in regards to the three cohorts that we talked about and the visibility. And then I'll ask -- hand it off to LeDuane, which, again, may take a quick second to talk about inventory levels and our targets and where we are today.

傑森，謝謝你的提問。我會盡力控制住局面。我會請喬希具體談談我們討論過的三個群體和可見性。然後我會問 - 將其交給 LeDuane，他可能需要花一點時間來談論庫存水平和我們的目標以及我們目前的狀況。

Jason, as we've mentioned, there are three distinct cohorts that we think about. The total prevalence for NPC is roughly 900 patients, 600 of which or so that are undiagnosed, living with the disease and don't even yet know it. And there are about 300 to 350 that are diagnosed in either receiving some sort of treatment or just sort of waiting and watching.

傑森，正如我們所提到的，我們考慮的是三個不同的群體。鼻咽癌的總患病人數約為 900 名患者，其中約 600 名患者未被診斷出患有該疾病，甚至還不知道自己患有該疾病。其中約有 300 至 350 人確診患有此病，要么接受某種治療，要么只是等待和觀察。

Of that subset, we had 83 patients who were in our expanded access program. And those patients have all been enrolled to receive MIPLYFFA. We reported at the end of the fourth quarter 109 patients, and that included those EAP patients plus a combination of diagnosed and undiagnosed. We continue to see a number of the two cohorts, the diagnosed and undiagnosed patients, coming in as a direct response to the initiatives that we've rolled out to bring more awareness to the disease and also to MIPLYFFA as a treatment option.

在這群患者中，有 83 名參加了我們的擴大准入計畫。這些患者均已報名接受 MIPLYFFA 治療。我們在第四季度末報告了 109 名患者，其中包括 EAP 患者以及確診和未確診的患者。我們不斷看到大量兩組患者（確診患者和未確診患者）前來就診，這是對我們推出的舉措的直接響應，旨在提高人們對這種疾病的認識，並將 MIPLYFFA 作為一種治療選擇。

LaDuane, if you can come off mute.

LaDuane，如果你能保持沉默的話。

Sure. Thank you. And so, Jason, with regard to inventory, these are the early days of the launch, and we seek to support patients and remain very nimble. So we're managing that closely using a target days on hand. When we reported out in Q4, we explained that we had reached it and stocked at that target level, and we are maintaining that as we come into the end of Q1 as well.

當然。謝謝。因此，傑森，就庫存而言，這是推出的早期階段，我們尋求支持患者並保持非常靈活的狀態。因此，我們利用現有目標天數來嚴密管理。當我們在第四季度發布報告時，我們解釋說我們已經達到了目標水平並保持了庫存，並且在進入第一季末時我們也會保持這一水平。

Great. Thanks for taking the questions.

偉大的。感謝您回答這些問題。

Eddie Hickman, Guggenheim.

古根漢美術館的艾迪希克曼。

Hey, good afternoon. Thanks for taking my questions and congrats on this progress so far. Any qualitative metrics on refill rates or patient retention or average net price that you can give us that might be helpful for modeling the durability and treatment effects or trajectory going into the second half of the year? Should we expect this cadence of de novo patients of maybe around three to four per month to continue throughout 2025? And what are the challenges in continuing to penetrate those non-EAP patients? Thanks.

嘿，下午好。感謝您回答我的問題，並祝賀迄今為止的進展。您能否提供任何有關補充率或患者保留率或平均淨價的定性指標，可能有助於模擬下半年的持久性和治療效果或軌跡？我們是否可以預期這種每月新增患者約三至四人的節奏會持續到 2025 年？那麼，繼續滲透那些非 EAP 患者面臨哪些挑戰？謝謝。

Yes. So I can give you a little bit of color to say that of those patients that have come in and for whom we've received enrollments and who are receiving active drug, the vast majority of them have received refills and are continuing to stay on drug. Certainly, as we continue through the launch, we would expect to see that maybe diminish a little bit. But it really -- if you reflect back to our EAP, we had patients who stayed on drug for as long as five to seven years, and so that really speaks to the clinical benefit of MIPLYFFA as well as the durability of response, and we would expect to see that commercially as well.

是的。因此，我可以給你一些信息，那就是在那些來就診、我們已經接收登記並正在接受活性藥物治療的患者中，絕大多數都已獲得續藥並將繼續服用藥物。當然，隨著發布的不斷進行，我們預計這種情況可能會減少。但事實上——如果你回顧一下我們的 EAP，我們有一些患者服用該藥物長達五到七年，所以這確實說明了 MIPLYFFA 的臨床益處以及反應的持久性，我們也希望在商業上看到這一點。

Your other questions were around net price. And again, what we're seeing in commercial is something very similar to the distribution of doses that we saw in the EAP, with the vast majority of patients receiving one or two of the higher doses. So that can give you kind of a sense of what the WAC price is and give you a sense of how that's trending as well.

您的其他問題與淨價有關。再次強調，我們在商業中看到的劑量分佈與我們在 EAP 中看到的劑量分佈非常相似，絕大多數患者接受一到兩次較高劑量。這樣您就可以大致了解 WAC 價格是多少，並了解其趨勢如何。

Yes, Eddie, before -- maybe you have a follow-up question here. But before we move forward, when we actually launched the program back in September, we talked about the fact that we were utilizing the average dosing of our EAP patients, which the clinical trial leaned more to younger, lighter-weight patients.

是的，艾迪，之前——也許你在這裡有一個後續問題。但在我們繼續前進之前，當我們在九月真正啟動該計劃時，我們談到了這樣一個事實，即我們正在利用 EAP 患者的平均劑量，而臨床試驗更傾向於年輕、體重較輕的患者。

And then our expanded access program really brought more adult patients in, too. What our real-world experience has been so far in the average pricing that we had reported out based on the weight distribution of our 83 patients has really kind of continued the same. So that guidance that we provided is guidance that I would continue to have you move forward with.

我們的擴大就診計畫也確實吸引了更多成年患者。到目前為止，我們根據 83 名患者的體重分佈報告的平均定價的實際經驗實際上與此相同。因此，我們提供的指導就是我將繼續讓您遵循的指導。

Thanks. And then I was curious about the cadence of those new patient starts throughout the year. Should we continue to think about 12 to 13 per quarter, or will that diminish or grow throughout the year?

謝謝。然後我很好奇這些新病人全年的開始節奏。我們是否應該繼續考慮每季 12 到 13 個，還是全年會減少或增加？

Thanks again for the question. I think it's difficult for us. We're not going to provide guidance. We're going to continue to be disciplined in what we do around the metrics that Josh talked about and new patient enrollment forms as well as market access and then revenue to be able to pull through. What I would say to you, though, is that as we went through the three cohorts and accelerating the expanded access programs and continuing to get them really rapidly enrolled, which we would originally think would take us 12 months, we got it done in the quarter just a little bit.

再次感謝您的提問。我認為這對我們來說很困難。我們不會提供指導。我們將繼續嚴格按照 Josh 談到的指標、新病患登記表、市場准入和收入來開展工作，以實現目標。不過，我想告訴你們的是，隨著我們完成了三個隊列，並加速了擴大准入計劃，並繼續快速地讓他們入學，我們最初認為這將需要 12 個月的時間，但我們在本季度就完成了一點點。

We're now in the process of getting to these two other cohorts, the diagnosed patients who have not been on therapy as well as those patients who have not yet been diagnosed. We've seen all three of those cohorts in Q1, and we expect that we'll continue to see all three of those cohorts -- well, not the EAP. Those are done. But the other two cohorts, those patients who are diagnosed and undiagnosed, continue as the strength of the product and the benefits lead to getting patients on therapy. So I can't give you guidance in terms of where the cadence is going to be, but I can tell you that the strong performance today is based on our data.

我們現在正在處理另外兩類患者，即已確診但尚未接受治療的患者以及尚未確診的患者。我們在第一季就看到了這三個群體，我們預計我們將繼續看到這三個群體——嗯，但不是 EAP。這些都完成了。但另外兩組患者，即已確診和未確診的患者，仍繼續接受治療，因為該產品的優點和益處促使患者接受治療。因此，我無法就節奏給您指導，但我可以告訴您，今天的強勁表現是基於我們的數據。

That's all right. Thank you so much.

沒關係。太感謝了。

(Operator Instructions) Lachlan Hanbury-Brown, William Blair.

（操作員指示）Lachlan Hanbury-Brown，William Blair。

Hey, guys. Thanks for taking the questions, and congrats on the progress. I wanted to ask on the coverage. You said 38% of lives are covered. Can you just elaborate on what that coverage looks like, what the requirements are? Did you contract for that? And maybe how much of an impact does having that coverage make in terms of the time to get a patient from sort of prescription enrollment form to actually on drug, because I assume it still requires a prior authorization?

嘿，大家好。感謝您回答問題，並祝賀您的進展。我想問一下報道的情況。您說 38% 的生命得到了保障。您能詳細說明一下該保險的具體內容以及要求嗎？您簽訂合約嗎？而且，就患者從填寫處方登記表到實際用藥的時間而言，這種保險可能有多大影響，因為我認為這仍然需要事先授權？

And then if I could just clarify as well, on the EAP patients, you said that they had all been enrolled. Just to clarify, are they all receiving drug through the commercial channel now, or are some of them still sort of in the benefits investigation stage?

然後，如果我也可以澄清一下，關於 EAP 患者，您說他們都已入組。只是想澄清一下，他們現在都是透過商業管道獲得藥物嗎，還是其中一些仍處於效益調查階段？

Great. Well, I'll take your first question around what the 38% of covered lives means. So again, most commercial plans and federal plans will evaluate a drug based on its clinical merits, and some plans will not, by policy, evaluate a product until it's been on the market for six months, and some it might be as long as 12 months. And so the 38% of covered lives means that those plans, roughly 75 to 100 plans out there covering several hundreds of millions of lives, have reviewed MIPLYFFA and have made it available to their patients. And that represents about 38% of the total lives out there that have insurance.

偉大的。好吧，我先回答你的第一個問題，38% 的受保生命意味著什麼。因此，大多數商業計劃和聯邦計劃將根據藥物的臨床價值對其進行評估，並且根據政策，有些計劃在產品上市六個月後才會對其進行評估，而有些計劃則可能需要長達 12 個月。因此，38% 的受保人次意味著這些計劃（大約有 75 到 100 個計劃，涵蓋數億人的生命）已經審查了 MIPLYFFA，並已將其提供給患者。這意味著擁有保險的總人數約佔 38%。

That does not mean that only 38% of our patients will receive drug or be able to get drug reimbursed. That just means that there's a direct route through a formulary status or position. All plans have a medical exception pathway, and we've been very successful in getting our patients reimbursed through a medical exception pathway. We expect that 38% to increase as more plans evaluate MIPLYFFA going forward, and we will continue to see that number increase, and we will continue to have patients reimbursed either through direct formulary status or through the medical exception pathway.

這並不意味著只有 38% 的患者能夠獲得藥物或獲得藥物報銷。這僅僅意味著有一條通過處方狀態或職位的直接途徑。所有計劃都有醫療例外途徑，並且我們在透過醫療例外途徑讓患者獲得報銷方面非常成功。我們預計，隨著越來越多的計劃對 MIPLYFFA 進行評估，這一數字將會增加 38%，而且我們將繼續看到這一數字增加，並且我們將繼續透過直接處方集狀態或醫療例外途徑為患者報銷。

Just to follow up on your question, you asked if all of the patient enrollment forms have been put onto a commercial product. And that's a process that we work through this medical exception pathway as well as others to get patients through and convert them from an enrollment form to a paid prescription, if you will, or commercial product. That timeline is not immediate. Some of them are within 24 hours. They can get through the process. And others take time to work through this peer-to-peer medical exception, so on, and so forth process of getting specialty pharmacy products through.

為了跟進您的問題，您詢問是否所有患者登記表都已放入商業產品中。這是我們透過這種醫療例外途徑以及其他途徑讓患者通過並將其從登記表轉換為付費處方或商業產品的過程。該時間表並不是立即的。有些是在 24 小時內。他們可以完成這個過程。其他人則需要花時間來完成這種點對點醫療例外等獲取專業藥品的過程。

What I'm very proud of is the team has actually worked diligently to be able to ensure that when a prescription form comes in, we do everything that we can to make sure that patient and their family receive the product as soon as possible while we're going through the benefits investigation process. And they're actually rapidly working through this really large number, again, 122 enrollment forms, a dramatic number of forms and really strong performance and getting through that process.

令我感到非常自豪的是，團隊實際上一直在努力工作，以確保在收到處方表時，我們會盡一切努力確保患者及其家人在我們進行福利調查過程時盡快收到產品。他們實際上正在快速處理數量龐大的 122 份入學表格，數量驚人，而且他們表現非常出色，順利完成了整個流程。

Some are going to take 30 days. Some are going to take 24 hours. Some are going to take 30 days. Some are going to take much longer than that. So I would say that right now, our team is doing a great job, and you see that based on the revenue numbers that we've got in just our first full-quarter post-launch of converting those patients.

有些需要 30 天。有些需要 24 小時。有些需要 30 天。有些則需要更長的時間。所以我想說，現在我們的團隊做得非常出色，從我們在轉換這些患者後的第一個完整季度所獲得的收入數字就可以看出這一點。

Thanks.

謝謝。

Sumant Kulkarni, Canaccord.

Sumant Kulkarni，Canaccord。

Thanks for the follow up. This is on celiprolol, which seems to be flying under the radar a little bit. You said you have 32 patients enrolled. It's an event-driven trial where you're increasing efforts to drive enrollment. If I remember right, this is a 150-patient trial. It looks like the last update on clinicaltrials.gov came about a year ago. Given that the Phase 3 trial for a competitor, Enzastaurin, has been suspended for some time now. What does that mean in terms of your ability to give us a timeline on when enrollment might be complete?

感謝您的跟進。這是關於塞利洛爾的，它似乎有點不受關注。您說您有 32 位患者入組。這是一項事件驅動的試驗，您將加強推動註冊。如果我沒記錯的話，這是一項有 150 名患者參與的試驗。看起來 clinicaltrials.gov 的最後一次更新大約是在一年前。鑑於競爭對手 Enzastaurin 的 3 期試驗已暫停一段時間。就您能否告訴我們何時可以完成招生而言，這意味著什麼？

Your numbers are absolutely accurate, Sumant. You talked about an n of 150 patients in a two-to-one randomization. I think it's important to just take a quick step back. We inherited this trial after it had actually paused enrollment for some time with a large number, as we've said publicly previously, of screenings that were ready to go into the trial. We kicked that off in Q3 with our first patients being reenrolled and redosed in the trial.

您的數字絕對準確，Sumant。您談到了二比一隨機分組的 150 名患者。我認為快速退一步很重要。我們在這項試驗暫停招募一段時間後接手了它，正如我們之前公開所說的，有大量的篩選結果已準備好投入試驗。我們從第三季開始這項試驗，第一批患者重新入組並重新服用藥物。

And then we've been actually investing in getting through the screening of the previous patients, but also now targeting how we're going to be able to drive and future enrollment. We talked about our ability to go to call 3A1 patient centers and physicians to be able to find more readily diagnosed patients who are more keen to be able to go into the trial. And we also talked about some genetic testing that we're also doing as part of our screening so we get more patients who are already diagnosed, have the genetic defect, and we can then offer them the opportunity to be in the trial.

然後，我們實際上一直在投資完成對先前患者的篩檢，但現在也致力於如何推動未來的招募。我們討論了我們聯繫 3A1 患者中心和醫生的能力，以便能夠找到更容易確診且更渴望參加試驗的患者。我們也討論了作為篩檢的一部分進行的一些基因檢測，以便我們能夠獲得更多已被診斷患有基因缺陷的患者，然後我們可以為他們提供參加試驗的機會。

Those activities, we feel very confident, will continue to drive and now accelerate enrollment of the trial. But it's really only been two quarters since we got the trial up and going, the learnings as we've walked through, and now we've got these five additional patients, 32 patients enrolled to date. And there's a high unmet need and no approved therapy, as you know, but we're working through with these clinics and testing centers now to really ramp it. In a nutshell, I can't tell you exactly when we will finalize it, but the strategies are starting to pay off in terms of our commitment to moving forward.

我們非常有信心，這些活動將繼續推動並加速試驗的招募。但實際上，從我們開始試驗到現在只過了兩個季度，我們在過程中累積了經驗，現在我們又有 5 名患者，迄今為止共有 32 名患者入組。如你所知，存在著很大的未滿足需求，也沒有批准的療法，但我們現在正在與這些診所和檢測中心合作，以真正提高治療效果。簡而言之，我無法確切地告訴您我們何時能夠完成它，但就我們向前邁進的承諾而言，這些策略已開始獲得回報。

Got it. Thanks.

知道了。謝謝。

And that will conclude the Q&A session. I want to now turn the program back over to Neil McFarlane for any additional or closing remarks.

問答環節到此結束。現在我想將節目交還給尼爾麥克法蘭 (Neil McFarlane)，請他發表任何補充或結束語。

Thanks, operator. And thanks, everybody, for joining our call today. We look forward to keeping you appraised of future progress and look to see you in Q2.

謝謝，接線生。感謝大家今天參加我們的電話會議。我們期待向您通報未來的進展，並期待在第二季見到您。

Thank you, sir. This does conclude today's program. We thank you for your participation. You may disconnect at any time.

謝謝您，先生。今天的節目到此結束。我們感謝您的參與。您可以隨時斷開連線。