Zevra Therapeutics Inc (ZVRA) 2023 Q2 法說會逐字稿

Good morning, and welcome to the Zevra Therapeutics Second Quarter 2023 Corporate and Financial Results Conference Call. (Operator Instructions) Please be advised that today's call is being recorded.

早上好，歡迎參加 Zevra Therapeutics 2023 年第二季度公司和財務業績電話會議。 （操作員說明）請注意，今天的通話正在錄音。

I will now turn the call over to Nichol Ochsner, Zevra Therapeutics Vice President, Investor Relations and Corporate Communications. Thank you. You may begin.

我現在將把電話轉給 Zevra Therapeutics 投資者關係和企業傳播副總裁 Nichol Ochsner。謝謝。你可以開始了。

Good morning, and thank you for joining us today to review Zevra Therapeutics progress in the second quarter of 2023, outlining our clinical progress, operational achievements, and financial results.

早上好，感謝您今天與我們一起回顧 Zevra Therapeutics 在 2023 年第二季度的進展，概述我們的臨床進展、運營成就和財務業績。

Before we get started, let me take a moment to provide some important information. First, I encourage you to access the webcast slides and the press release both of which were released this morning and are available in the Investors Section of Zevra's website. These documents provide comprehensive insights into our results for this quarter.

在我們開始之前，讓我花點時間提供一些重要信息。首先，我鼓勵您訪問今天上午發布的網絡廣播幻燈片和新聞稿，可在 Zevra 網站的投資者部分獲取。這些文件提供了對我們本季度業績的全面見解。

As we move forward with the presentation, it is important to highlight that today's discussions will include forward-looking statements. These encompass various topics, including updates on clinical development, and regulatory journey of arimoclomol, the achievements and revenue milestones of AZSTARYS, and our French Early Access Program or EAP program. The achievement of our pipeline programs, time lines for clinical trial enrollment, initiation, completion and data reporting from our clinical trials. However, forward-looking statements are not promises or guarantees and are inherently subject to risks, uncertainties and other significant factors that may lead to actual results differing materially from those projections made. For a comprehensive understanding of these factors, please refer to the Risk Factors section of our annual report on Form 10-K.

隨著我們繼續進行演示，重要的是要強調今天的討論將包括前瞻性陳述。這些內容涵蓋各種主題，包括臨床開發的最新情況、arimoclomol 的監管歷程、AZSTARYS 的成就和收入里程碑，以及我們的法國早期訪問計劃或 EAP 計劃。我們的管道計劃的實現、臨床試驗註冊、啟動、完成和臨床試驗數據報告的時間表。然而，前瞻性陳述並非承諾或保證，本質上會受到風險、不確定性和其他重大因素的影響，這些因素可能導致實際結果與預測存在重大差異。要全面了解這些因素，請參閱我們 10-K 表年度報告的風險因素部分。

I am pleased to welcome Zevra's management team members participating in today's call. I'm joined by Christal Mickle, our Co-Founder, Chief Development Officer and interim Chief Executive Officer. LaDuane Clifton, our Chief Financial Officer; and Josh Schafer, our Chief Commercial Officer and Executive Vice President of Business Development.

我很高興歡迎 Zevra 的管理團隊成員參加今天的電話會議。我們的聯合創始人、首席開發官兼臨時首席執行官 Christal Mickle 也加入了我的行列。 LaDuane Clifton，我們的首席財務官；以及我們的首席商務官兼業務開發執行副總裁 Josh Schafer。

Now I'd like to turn the call over to Christal Mickle.

現在我想把電話轉給 Christal Mickle。

Thank you, Nichol. Good morning, and thank you all for joining us today. The year-to-date has been a dynamic time for Zevra and second quarter was quite productive for our team. We're very encouraged by the continued advancement of our rare disease pipeline programs towards multiple near-term clinical and regulatory milestones as well as by the progress that we are making to add in-house commercial capabilities needed to bring therapies to market directly. In addition, we continue to enhance our patient advocacy efforts, which include ongoing support of our early access programs for arimoclomol.

謝謝你，尼科爾。早上好，感謝大家今天加入我們。今年迄今為止對 Zevra 來說是一個充滿活力的時期，第二季度對我們的團隊來說非常富有成效。我們的罕見病管道項目朝著多個近期臨床和監管里程碑的持續進展，以及我們在增加將療法直接推向市場所需的內部商業能力方面所取得的進展感到非常鼓舞。此外，我們繼續加強患者宣傳工作，其中包括持續支持我們的阿莫洛莫早期使用計劃。

Nichol, can you advance to the next slide, please?

Nichol，您可以轉到下一張幻燈片嗎？

Our balance sheet remains strong, and we believe that we have made solid progress towards our strategic mission of delivering much-needed innovative therapy to people with rare diseases. An important update today is regarding our progress with the resubmission of the NDA for arimoclomol. Our product candidate for the treatment of Niemann-Pick Disease Type C or NPC.

我們的資產負債表仍然強勁，我們相信我們在實現為罕見疾病患者提供急需的創新療法的戰略使命方面取得了堅實的進展。今天的一個重要更新是關於我們重新提交阿莫洛莫 NDA 的進展情況。我們的候選產品用於治療 C 型尼曼匹克病或鼻咽癌。

Earlier this month, we participated in a pre-submission meeting with the FDA, which focused on a preview of the complete package that we anticipate resubmitting for review. The meeting was productive and collaborative, and we gain valuable insight that we believe will help us to complete the package and give us our best chance for success. Our strategy for resubmission remains unchanged, and we are targeting resubmission by the end of this year.

本月早些時候，我們參加了 FDA 的提交前會議，會議重點是預覽我們預計重新提交審查的完整方案。這次會議富有成效和協作性，我們獲得了寶貴的見解，我們相信這些見解將幫助我們完成一攬子計劃，並為我們提供成功的最佳機會。我們的重新提交策略保持不變，我們的目標是在今年年底前重新提交。

Regarding the development program for KP1077, our product candidate intended for the treatment of IH and narcolepsy. Our Phase II trial in IH is advancing with interim data expected by the end of this quarter. And we look forward to sharing that information as soon as it's available. Based on the pace of enrollment, top line results for the Phase II trial are expected to be available during the first half of 2024. In addition, the IND opening Phase I trial in our narcolepsy program has been initiated with enrollments now underway.

關於 KP1077 的開發計劃，我們的候選產品旨在治療 IH 和發作性睡病。我們的 IH II 期試驗正在推進，預計將在本季度末獲得中期數據。我們期待盡快分享該信息。根據入組進度，第二階段試驗的主要結果預計將在 2024 年上半年獲得。此外，我們的發作性睡病項目中的 IND 開放第一階段試驗已經啟動，目前正在進行入組。

We ended the second quarter with a solid financial position. As of June 30, 2023, cash, cash equivalents and investments were $87.4 million, which supports our forecasted operating cash runway into 2026. In addition, year-to-date net sales of AZSTARYS surpassed $25 million, triggering the first net sales milestone payment of $5 million, which was received after quarter end this month. Earning the first net sales milestone for the AZSTARYS program was an important milestone, providing momentum towards the possibility of earning a second net sales milestone in 2023. Our balance sheet continues to be a source of strength for our business, especially given the prevailing conditions of the capital markets.

我們以穩健的財務狀況結束了第二季度。截至2023 年6 月30 日，現金、現金等價物和投資為8740 萬美元，這支持了我們預測的2026 年運營現金跑道。此外，AZSTARYS 年初至今的淨銷售額超過2500 萬美元，觸發了第一筆淨銷售額里程碑付款500 萬美元，於本月季度結束後收到。 AZSTARYS 計劃實現第一個淨銷售額里程碑是一個重要的里程碑，為2023 年實現第二個淨銷售額里程碑提供了動力。我們的資產負債表仍然是我們業務實力的源泉，特別是考慮到當前的情況資本市場。

To round out recent events, just last week, we welcomed Tom Anderson to our Board of Directors. He is a highly accomplished industry veteran with both commercial and rare disease expertise, and in addition, is another important step within the ongoing Board refreshment plan. As we welcome Tom to our Board, we also want to express our gratitude to retiring board member, Matt Plooster. Matt has been with the company since before our initial public offering in April 2015, and his efforts to play a fundamental role in shaping our growth and advancing our mission. As a co-founder of Zevra, I want to extend my personal thanks to you, Matt, for your many years of service. As we move forward, the Board continues to be unified in its support of Zevra's rare disease strategy.

為了結束最近的活動，就在上週，我們歡迎湯姆·安德森 (Tom Anderson) 加入我們的董事會。他是一位成就卓著的行業資深人士，擁有商業和罕見疾病方面的專業知識，此外，他也是正在進行的董事會更新計劃中的另一個重要步驟。在我們歡迎 Tom 加入董事會的同時，我們還要向即將退休的董事會成員 Matt Plooster 表示感謝。 Matt 自 2015 年 4 月首次公開募股之前就一直在公司工作，他努力在塑造我們的發展和推進我們的使命方面發揮基礎性作用。作為 Zevra 的聯合創始人，我想對您多年來的服務表達我個人的謝意。隨著我們的前進，董事會將繼續一致支持 Zevra 的罕見病戰略。

Now more than ever, developing and commercializing therapies for rare diseases with the patient's first approach remains our mission as we work to build a best-in-class rare disease company.

現在，我們比以往任何時候都更加註重以患者為先的方法來開發和商業化罕見疾病療法，這仍然是我們的使命，因為我們致力於打造一流的罕見疾病公司。

Since acquiring arimoclomol, our team has been engaged in multiple interactions with the FDA as we prepare an optimized NDA data package showcasing the safety and efficacy of arimoclomol. As I've mentioned previously, earlier this month, we held a pre-submission meeting with the FDA. We were encouraged by the productive and collaborative nature of the meeting, and we received important guidance from the agency that we will incorporate in the NDA package. As a result, we have refined our expectations that we will resubmit the full NDA to the FDA by the end of this year.

自從收購阿莫洛莫以來，我們的團隊一直與 FDA 進行多次互動，準備了優化的 NDA 數據包，展示了阿莫洛莫的安全性和有效性。正如我之前提到的，本月早些時候，我們與 FDA 舉行了一次提交前會議。我們對這次會議的富有成效和協作性感到鼓舞，並且我們收到了該機構的重要指導，我們將把這些指導納入 NDA 一攬子計劃中。因此，我們調整了我們的預期，即我們將在今年年底前向 FDA 重新提交完整的 NDA。

As you may recall, the Complete Response Letter that Orphazyme received from the FDA in June of 2021 identified 3 main issues. The first issue was related to the validation and reliability of the NPCCSS instrument in measuring NPC disease progression. To address this issue, we plan to provide additional evidence to support the use of the scale as the primary instrument used in the efficacy trial. For example, the FDA confirmed that it is acceptable to conduct a new analysis of the original 5-domain NPCCSS by removing the cognition domain. The FDA also encouraged the company to conduct a qualitative study to assess the validity and robustness of the swallowing domain.

您可能還記得，Orphazyme 於 2021 年 6 月從 FDA 收到的完整回复函確定了 3 個主要問題。第一個問題與 NPCCSS 儀器在測量 NPC 疾病進展方面的驗證和可靠性有關。為了解決這個問題，我們計劃提供額外的證據來支持使用量表作為功效試驗中使用的主要工具。例如，FDA確認通過刪除認知域來對原始5域NPCCSS進行新的分析是可以接受的。 FDA 還鼓勵該公司進行定性研究，以評估吞嚥領域的有效性和穩健性。

The second issue that was related -- the second issue was related to the appropriateness of how to handle data affected by certain patient events and the method of primary endpoint analysis. To address this issue, we will be using an FDA preferred primary analysis together with additional supportive analyses.

相關的第二個問題——第二個問題與如何處理受某些患者事件影響的數據以及主要終點分析方法的適當性有關。為了解決這個問題，我們將使用 FDA 首選的初步分析以及其他支持性分析。

The third issue is related to the strength of the confirmatory evidence to support a single efficacy study. To address the third issue, we plan to provide additional data from multiple new nonclinical studies as well as data from the 4-year open-label extension of the Phase II/III clinical trial. The recent interaction with the FDA was constructive and provided us with additional information that we believe will further bolster the quality of our resubmission and ultimately support regulatory success for the benefit of the NPC community.

第三個問題與支持單一功效研究的確證性證據的強度有關。為了解決第三個問題，我們計劃提供來自多項新的非臨床研究的額外數據以及來自 II/III 期臨床試驗 4 年開放標籤擴展的數據。最近與 FDA 的互動是建設性的，為我們提供了更多信息，我們相信這些信息將進一步提高我們重新提交的質量，並最終支持監管成功，造福 NPC 群體。

In parallel with the preparation of the NDA resubmission, we are laying the groundwork for the potential commercial launch of arimoclomol in the U.S. is approved. With the goal of making this groundbreaking therapy accessible to patients as soon as possible.

在準備重新提交 NDA 的同時，我們正在為阿莫洛莫在美國獲得批准的潛在商業上市奠定基礎。目標是讓患者盡快獲得這種突破性的療法。

There are several strategic imperatives to ensure a successful arimoclomol launch. We are working to develop the NPC market through disease awareness with payers and prescribers. We believe patients can benefit from arimoclomol through key patient finding initiatives, such as genetic testing programs, early diagnosis tools such as newborn screening, and the development of other patient identification guidelines and resources.

確保阿莫洛莫的成功上市有幾個戰略要務。我們正在努力通過付款人和處方者的疾病意識來開發 NPC 市場。我們相信，通過關鍵的患者發現舉措，例如基因檢測計劃、新生兒篩查等早期診斷工具以及開發其他患者識別指南和資源，患者可以從阿莫洛莫中受益。

We also work to establish arimoclomol as a foundational treatment for NPC patients by continuing to engage key opinion leaders and educating treating physicians of its clinical profile. Our goal is to decrease the time from diagnosis to treatment through market access and create a best-in-class patient and caregiver experience through education, patient services and reimbursement assistance.

我們還通過繼續與關鍵意見領袖合作並向治療醫生介紹其臨床概況，努力將阿莫洛莫建立為鼻咽癌患者的基礎治療方法。我們的目標是通過市場准入縮短從診斷到治療的時間，並通過教育、患者服務和報銷援助創造一流的患者和護理人員體驗。

We are developing a tailored patient services program to support insurance approvals, patient access and positive treatment experiences. And we will seek to continue our close collaboration with key stakeholders including key opinion leaders and patient advocates to establish Zevra as a trusted and committed partner within the NPC community.

我們正在開發量身定制的患者服務計劃，以支持保險審批、患者獲取和積極的治療體驗。我們將尋求繼續與關鍵利益相關者（包括關鍵意見領袖和患者倡導者）密切合作，將 Zevra 打造成 NPC 社區中值得信賴和忠誠的合作夥伴。

Throughout this journey, we are committed to working on inside people with NPC, their families and caregivers, advocates and medical community members. We are extremely grateful for everyone who continues to participate in trials FDA meetings and discussions and all of those who are supporting the development of treatments for NPC.

在整個過程中，我們致力於為 NPC 內部人員、他們的家人、護理人員、倡導者和醫學界成員提供幫助。我們非常感謝所有繼續參加 FDA 試驗會議和討論的人以及所有支持鼻咽癌治療方法開發的人。

Now let's turn our attention to KP1077. Our development program for rare sleep disorders. Beginning with idiopathic hypersomnia, or IH, we are pleased to report that our Phase II clinical trial evaluating KP1077 is progressing nicely. We are currently enrolling at over 30 sites across the U.S. As you may recall, the trial is a dose optimizing double-blind, placebo-controlled randomized-withdrawal study to evaluate the safety of KP1077 as well as potential efficacy endpoints such as sleepiness, brain fog and sleep inertia.

現在讓我們把注意力轉向KP1077。我們針對罕見睡眠障礙的開發計劃。從特發性嗜睡症（IH）開始，我們很高興地報告，我們評估 KP1077 的 II 期臨床試驗進展順利。我們目前正在美國30 多個地點進行招募。您可能還記得，該試驗是一項劑量優化雙盲、安慰劑對照隨機停藥研究，旨在評估KP1077 的安全性以及潛在的療效終點，例如嗜睡、大腦霧和睡眠慣性。

Interim Phase II data that will be used to inform the design of the Phase III clinical trial are expected by the end of Q3 2023. Potential key differentiators include alignment of peak efficacy with patient need through dose optimized timing and expanded exposure range through unique pharmacokinetics. Based on the current pace of enrollment, we anticipate reporting top line data for the Phase II trial sometime during the first half of next year.

預計將於2023 年第三季度末獲得中期II 期數據，用於為III 期臨床試驗的設計提供信息。潛在的關鍵差異化因素包括通過劑量優化時間調整峰值療效與患者需求，以及通過獨特的藥代動力學擴大暴露範圍。根據目前的入組速度，我們預計將在明年上半年的某個時候報告第二階段試驗的主要數據。

In addition to the ongoing Phase II trial in IH, we expanded our KP1077 clinical program in April by opening an investigational new drug application, or IND, in narcolepsy. With the goal of exploring the possibility of adding an indication for narcolepsy and thereby expanding the potential that KP1077 could address multiple sleep disorders.

除了正在進行的 IH II 期試驗外，我們還在 4 月份擴大了 KP1077 臨床計劃，啟動了一項針對發作性睡病的研究性新藥申請（IND）。目標是探索增加發作性睡病適應症的可能性，從而擴大 KP1077 解決多種睡眠障礙的潛力。

The IND opening study, which is a Phase I clinical trial in healthy adults was initiated during the second quarter and enrollment has begun. As we move forward with programs in both IH and narcolepsy, we plan to evaluate the potential to initiate a Phase III trial in narcolepsy by seeking to leverage key data points from our IH program as well as leaning on the robust data generated for serdexmethylphenidate or SDX, as part of the AZSTARYS development program.

IND 開放研究是在健康成人中進行的 I 期臨床試驗，於第二季度啟動，並已開始入組。隨著我們推進 IH 和嗜睡症項目，我們計劃通過尋求利用我們的 IH 項目的關鍵數據點以及依靠哌醋甲酯或 SDX 生成的可靠數據來評估啟動嗜睡症 III 期試驗的可能性，作為AZSTARYS 開發計劃的一部分。

As you may recall, SDX is a sole active pharmaceutical ingredient in KP1077. This strategic approach is aimed at enhancing our efficiency in developing KP1077 and bringing this potentially life-changing therapy to people in need across both indications. As you can see, we have been working diligently to drive progress in our regulatory and development programs.

您可能還記得，SDX 是 KP1077 中的唯一活性藥物成分。這一戰略方法旨在提高我們開發 KP1077 的效率，並將這種可能改變生活的療法帶給有需要的人，涵蓋這兩種適應症。正如您所看到的，我們一直在努力推動我們的監管和開發計劃取得進展。

Now I'll hand the call over to LaDuane, who will provide an update on our financial results and outlook. LaDuane?

現在我將把電話轉交給拉杜安，他將提供我們財務業績和前景的最新信息。拉杜安？

Thanks, Christal, and good morning, everyone. As Christal mentioned, we are pleased to announce that AZSTARYS has reached a key milestone in the second quarter, surpassing $25 million in annual net sales for the first time. This achievement triggered a $5 million milestone payment to Zevra, which has also been received after quarter end in August 2023. This underscores the growing demand for this important therapy within the ADHD treatment landscape.

謝謝克里斯塔爾，大家早上好。正如 Christal 提到的，我們很高興地宣布 AZSTARYS 在第二季度達到了一個重要的里程碑，年度淨銷售額首次超過 2500 萬美元。這一成就觸發了向 Zevra 支付的 500 萬美元里程碑付款，這筆款項也在 2023 年 8 月季度末後收到。這突顯了 ADHD 治療領域對這種重要療法的需求不斷增長。

We also earned royalties on net sales of $800,000 for the second quarter, and we are encouraged to see AZSTARYS continuing to attain new record weekly prescription counts. With the momentum that AZSTARYS is exhibiting through second quarter, the trend supports the potential to earn a second net sales milestone by the end of 2023. We also anticipate that the quarterly royalties on net sales will continue to grow over the next several years. Beyond the first and second net sales milestones, there are several more, we believe are attainable in the near future bringing the potential to drive increased value for our shareholders.

我們還獲得了第二季度 800,000 美元淨銷售額的特許權使用費，我們很高興看到 AZSTARYS 繼續創下每周處方數新紀錄。憑藉 AZSTARYS 在第二季度表現出的勢頭，這一趨勢支持到 2023 年底實現第二個淨銷售額里程碑的潛力。我們還預計，淨銷售額的季度特許權使用費將在未來幾年繼續增長。除了第一個和第二個淨銷售額里程碑之外，我們相信在不久的將來還可以實現更多里程碑，從而為我們的股東帶來增加價值的潛力。

For Q2 2023, net revenue was $8.5 million, which was driven by the $5.8 million from AZSTARYS including the net sales milestone and royalties earned in the second quarter and $2.8 million in reimbursements from the French Early Access Program for arimoclomol. We ended with a net loss for Q2 of 2023, which was $5.1 million or $0.15 per basic and diluted share, driven primarily by R&D expenses of $7.4 million and G&A expenses of $7 million offset in part by the $8.5 million in revenue and $1.5 million in other income.

2023 年第二季度，淨收入為850 萬美元，主要由AZSTARYS 的580 萬美元推動，其中包括第二季度的淨銷售里程碑和特許權使用費，以及法國阿莫洛莫早期訪問計劃的280 萬美元報銷。我們結束了2023 年第二季度的淨虧損，為510 萬美元或每股基本股和稀釋股0.15 美元，這主要是由於740 萬美元的研發費用和700 萬美元的一般管理費用部分被850 萬美元的收入和150 萬美元的營收所抵消。其他的收入。

R&D expenses reflect the ongoing investments in the KP1077 clinical program as well as our ongoing work to prepare the arimoclomol NDA for resubmission to the FDA. G&A expenses reflect the investments we're making in our in-house commercial capabilities as well as operational support needed to underpin the need of our team as we prepare for success.

研發費用反映了對 KP1077 臨床項目的持續投資，以及我們正在進行的準備阿莫洛莫新藥申請以重新提交給 FDA 的工作。一般管理費用反映了我們對內部商業能力的投資，以及在我們為成功做準備時支持我們團隊的需求所需的運營支持。

As of June 30, 2023, total cash, cash equivalents and investments were $87.4 million, a decrease of $7.9 million compared to $95.3 million as of March 31, 2023. The decrease was driven in part by increased third-party R&D costs related to the ongoing Phase II trial for KP1077. The arimoclomol program and increased G&A expenses during the period. Of note, our available cash as of June 30, 2023, does not include the cash payment of the $5 million net sales milestone from AZSTARYS, which was received at the quarter end.

截至 2023 年 6 月 30 日，現金、現金等價物和投資總額為 8,740 萬美元，比截至 2023 年 3 月 31 日的 9,530 萬美元減少 790 萬美元。這一下降的部分原因是與正在進行KP1077 的II期試驗。在此期間阿莫洛莫計劃和一般管理費用增加。值得注意的是，截至 2023 年 6 月 30 日，我們的可用現金不包括 AZSTARYS 於季度末收到的 500 萬美元淨銷售額里程碑的現金支付。

The total shares of common stock outstanding as of June 30 were 33,928,005 and the fully diluted common shares outstanding were 49,315,197, which includes about 4.3 million shares issuable upon exercise of warrants.

截至6月30日，已發行普通股總數為33,928,005股，完全稀釋後已發行普通股為49,315,197股，其中包括約430萬股因行使認股權證而發行的股份。

The company's current operating forecast, existing cash and cash equivalents and investments are expected to support our cash runway into 2026. Our forecast includes the ongoing reimbursements from the print early access program for arimoclomol, completion of the arimoclomol-NDA resubmission, commercial activities to support the launch of arimoclomol, if approved, and completion of the 1077 development program for IH up to and including NDA submission.

公司當前的運營預測、現有現金和現金等價物以及投資預計將支持我們到2026 年的現金跑道。我們的預測包括阿莫洛莫印刷版早期訪問計劃的持續報銷、阿莫洛莫新藥申請的重新提交的完成、支持的商業活動如果獲得批准，將推出阿莫洛莫，並完成 IH 的 1077 開發計劃，包括 NDA 提交。

Our forecast notably does not include revenue from arimoclomol or the potential sale of the priority review voucher, which would be received upon approval of arimoclomol. It also does not include the investments needed if we determined to proceed with a Phase III trial for KP1077 in narcolepsy. Zevra remains committed to strategic financial management, focusing on prudent approach -- prudent approach to capital allocation to support the advancement of our pipeline programs and ensure the successful development of transformative therapies.

我們的預測特別不包括來自阿莫洛莫的收入或優先審評券的潛在銷售，這些收入將在阿莫洛莫獲得批准後收到。它還不包括如果我們決定繼續進行 KP1077 治療發作性睡病的 III 期試驗所需的投資。 Zevra 仍然致力於戰略財務管理，注重審慎的方法——審慎的資本配置方法，以支持我們的管道項目的進展並確保變革療法的成功開發。

In addition, we continue to be vigilant in our business development efforts. We continue to scan for opportunities where, in addition to our internal development programs, we may be able to add other rare disease product candidates to our pipeline. As we look forward to the second half of this year and into next year, there are multiple catalysts that have the potential to deliver value for our shareholders. We are encouraged by our progress to date.

此外，我們在業務發展工作中繼續保持警惕。我們繼續尋找機會，除了我們的內部開發計劃之外，我們還可以將其他罕見疾病候選產品添加到我們的管道中。當我們展望今年下半年和明年時，有多種催化劑有可能為我們的股東帶來價值。我們對迄今為止所取得的進展感到鼓舞。

And with that, we will now return the call to the operator for questions.

現在，我們將向接線員回電以詢問問題。

(Operator Instructions) We will take our first question from Louise Chen with Cantor.

（操作員說明）我們將回答 Louise Chen 和 Cantor 提出的第一個問題。

This is [Harvey] on for Louise from Cantor. My first question is on a potential second net sales milestone you might achieve in 2023. How big is this potential milestone.

我是[哈維]為來自康託的路易絲發言。我的第一個問題是關於您可能在 2023 年實現的第二個淨銷售額里程碑。這個潛在里程碑有多大。

Secondly, what are the expectations heading into the interim Phase II IH readout, what caused it to be a home run scenario?

其次，對第二階段 IH 中期讀數的期望是什麼，是什麼導致它成為全壘打？

Well, thanks for your question, and I'll take the first one, Christal. The second milestone, we've not been able to disclose its magnitude or the sales threshold that we have to achieve in order to earn that milestone, but I think it's safe to say that it will be larger than the one we just earned in Q2, which was $5 million. So I'm a bit limited there, but I think that we can look forward to a continued sort of growth not only in net sales, but also in royalties, and the size of the milestones. Christal?

好吧，謝謝你的問題，我會回答第一個問題，Christal。第二個里程碑，我們無法透露其規模或我們必須達到的銷售門檻才能獲得該里程碑，但我認為可以肯定地說它將比我們在第二季度剛剛獲得的更大，這是 500 萬美元。所以我的能力有限，但我認為我們不僅可以期待淨銷售額、特許權使用費和里程碑規模的持續增長。克里斯塔爾？

Yes. Great. And as far as your question regarding the interim data, as you may remember, the point of the interim data is really to inform us on the Phase III trial moving forward. And so what we're really interested in is looking at the multiple dosings that we're looking at. So if you remember, we're looking at either a once dosing and the evening prior to going to sleep or twice dosing once in the evening and before waking.

是的。偉大的。至於你關於中期數據的問題，你可能還記得，中期數據的目的實際上是告訴我們第三階段試驗的進展情況。因此，我們真正感興趣的是我們正在研究的多重劑量。因此，如果您還記得的話，我們正在研究要么在晚上睡覺前服用一次，要么在晚上和醒來前服用兩次。

So looking at that and then also looking at the doses that are being used and seeing that those doses are higher than, than what is being used for other stimulants that are out there and making sure that we're in the right range for us as we move forward.

因此，看看這一點，然後再看看正在使用的劑量，看看這些劑量高於其他興奮劑的使用劑量，並確保我們處於正確的範圍內，因為我們繼續前進。

And our next question comes from Oren Livnat with H.C. Wainwright.

我們的下一個問題來自 Oren Livnat 和 H.C.溫賴特。

Congrats on the AZSTARYS progress. But I wanted to focus on arimoclomol. I just want to make sure I'm hearing correctly, not misinterpreting. I think you said in terms of how to deal with missing data and certain patient events. You said you're going to move forward with the FDA preferred primary analysis. I can't remember if that's like a change from your prior expectations or ambitions. I know there was a couple of different (inaudible) you had highlighted earlier when you did the deal, sort of like a rescored without cognition, some swallowing changes versus sort of an FDA analysis, which I think originally had a different p-value. And so can you just help us understand what compromises were made? What changes, if any, were there? And I have a follow-up.

祝賀 AZSTARYS 取得進展。但我想專注於阿莫洛莫。我只是想確保我聽得正確，而不是誤解。我認為您所說的是如何處理丟失的數據和某些患者事件。您說過您將繼續進行 FDA 首選的初步分析。我不記得這是否意味著你之前的期望或抱負發生了變化。我知道您之前在進行交易時強調了一些不同的（聽不清），有點像沒有認知的重新評分，一些吞嚥變化與 FDA 分析的比較，我認為最初有不同的 p 值。那麼你能幫助我們了解做出了哪些妥協嗎？如果有的話，有哪些變化？我有一個後續行動。

Appreciate the question. So no, we actually are continuing with our strategy as we're moving forward with the resubmission. So going with the FDA recommended analysis is not something that is new. And then when you -- we're talking about the validation and those other points, those are also things that are -- that will be included in the NDA. So those are all still moving ahead as we had originally planned to do.

感謝這個問題。所以不，我們實際上正在繼續我們的策略，因為我們正在推進重新提交。因此，採用 FDA 推薦的分析並不是什麼新鮮事。然後，當我們談論驗證和其他要點時，這些也將包含在 NDA 中。所以這些都仍在按照我們最初的計劃進行。

Okay. And so the timing change, which is not material necessarily, but I'm just curious if that's just more calibrating after your meeting with the FDA? Or is there a new stuff you've been working on, whether it's nonclinical stuff in animals or just analysis or reanalysis of the data?

好的。所以時間上的改變，這不一定是實質性的，但我只是好奇，在你與 FDA 會面後，這是否只是更加校準？或者您一直在研究新的東西，無論是動物的非臨床研究還是只是對數據的分析或再分析？

So it really boils down to -- we had our FDA meeting very recently, and so it's a refinement of making sure that we present the data in a way that the FDA would like to see it. And so with that, there are a few additional analyses. There's refinement in the way that we're presenting our arguments and our data. So even though what we're planning to present hasn't changed, there is some nuances there that we are going to look at. And so that pushes that a little bit out from that end of Q3 that we had originally talked about.

因此，歸根結底，我們最近召開了 FDA 會議，因此這是一項改進，以確保我們以 FDA 希望看到的方式呈現數據。因此，還有一些額外的分析。我們提出論點和數據的方式有所改進。因此，儘管我們計劃展示的內容沒有改變，但我們還是要考慮一些細微差別。因此，這比我們最初討論的第三季度末的情況稍微晚一些。

Okay. And I guess to characterize this meeting as, I think, collaborative or productive or both, which is great. I think in the past, maybe -- I don't know if it's in response to questions or if you volunteered upfront, you talked about, if necessary, you could take, I guess, less collaborative or more aggressive approach with dispute resolution and things like that, if necessary, is -- am I detecting a change in tone here because of that was mentioned or in the deck, I don't think that you feel actually more optimistic now, maybe after your meeting with the FDA, then than you did before and that you don't think you're going to have to pursue anything like that? And do you expect to request an ADCOM sort of upfront?

好的。我想，我認為這次會議是協作性的、富有成效的，或者兩者兼而有之，這非常棒。我想在過去，也許——我不知道這是為了回答問題，還是你事先自願提出的，你談到，如果有必要，我想你可以採取更少合作或更積極的方式來解決爭議，類似的事情，如果有必要的話，是——我是否發現這裡的語氣發生了變化，因為提到的或在甲板上，我不認為你現在實際上感到更樂觀，也許在你與FDA 會面之後，然後比你以前做的更好，並且你認為你不需要追求這樣的事情？您是否希望預先請求 ADCOM？

So to answer your first question, those options are always still available and still on the table. We do -- we were hopeful with this meeting that we had because it was a collaborative meeting, we were appreciative of the tone that the FDA had. And so they do seem to be working with us to get this resubmission in. And then as far as -- what was your second point there or your last point?

因此，回答你的第一個問題，這些選項始終仍然可用並且仍然在桌面上。我們確實對這次會議充滿希望，因為這是一次合作會議，我們對 FDA 的基調表示讚賞。因此，他們似乎確實正在與我們合作，重新提交。然後，您的第二點或最後一點是什麼？

Whether you expect, I guess, upfront to request an FDA, an ADCOM meeting...

我想，無論您是否期望預先請求 FDA、ADCOM 會議……

So that's an interesting question. I don't think we will as for upfront. We welcome it if it comes from the FDA, and that's still a consideration if the FDA does not ask for it that we may ask for it ourselves, but it's not something that we'll ask for immediately upon resubmission.

這是一個有趣的問題。我認為我們不會提前。如果它來自 FDA，我們表示歡迎，如果 FDA 不要求，這仍然是一個考慮因素，我們可能會自己要求，但我們不會在重新提交後立即要求。

Okay. And if I just may look a little further down the line, assuming this all goes well. Any progress that (inaudible) talking about on remarkable life cycle management. I think there was some hopes to improve dosing, get some more additional IP around the project? Anything to report there?

好的。假設一切順利，我可以再往下看一點。 （聽不清）談論卓越生命週期管理方面的任何進展。我認為有人希望改進劑量，圍繞該項目獲得更多額外的知識產權？那裡有什麼要報告的嗎？

So right now, we are focused on approval. But those are always things that we will look for as we move forward.

所以現在我們的重點是批准。但這些始終是我們前進過程中會尋找的東西。

(Operator Instructions) Our next question comes from Sumant Kulkarni with Canaccord.

（操作員說明）我們的下一個問題來自 Canaccord 的 Sumant Kulkarni。

I have a couple. So on the [lease] commitment of the arimoclomol NDA, you mentioned the productive and collaborative process with the FDA, which portion of the 3 parts of the Complete Response Letter and your ongoing response. Would you say that the majority of your last interaction with the FDA was focused on? And then I have a follow-up.

我有一對。因此，在 arimoclomol NDA 的[租賃]承諾中，您提到了與 FDA 的富有成效的合作過程，完整回复信的 3 個部分中的哪一部分以及您正在進行的回复。您是否認為您上次與 FDA 的互動主要集中在？然後我有一個後續行動。

So we really -- we presented everything because we did treat this as a pre-submission meeting, but we have -- a large part of it was also focused on the confirmatory evidence that the FDA hasn't seen in the past.

所以我們確實--我們展示了所有內容，因為我們確實將其視為提交前會議，但我們--其中很大一部分也集中在 FDA 過去沒有見過的確認性證據上。

Got it. And then in the last meeting with the FDA, did the agency state specifically that no additional clinical data would be required, or did the FDA making suggestions that additional clinical data that may be required but left to the discussion of Zevra on whether to run those are not prior to these submission?

知道了。然後在上次與 FDA 的會議上，該機構是否明確表示不需要額外的臨床數據，或者 FDA 是否建議可能需要額外的臨床數據，但留給 Zevra 討論是否運行這些數據這些不是之前提交的嗎？

There was no discussion about additional clinical data being needed.

沒有討論是否需要額外的臨床數據。

And our next question comes from Jonathan Aschoff with ROTH MKM.

我們的下一個問題來自 ROTH MKM 的 Jonathan Aschoff。

I was curious, so that was just the [$670,000] booking for AZSTARYS revenue versus [$630] in the prior quarter. I was just kind of curious if that math is correct, because you said arimoclomol was $2.8 million, $5 million milestone, just leave [$670]. Why was that kind of flat like that after the growth in the last couple of quarters?

我很好奇，所以這只是 AZSTARYS 收入的 [670,000 美元] 預訂，而上一季度的 [630 美元]。我只是有點好奇這個數學是否正確，因為你說阿莫洛莫是 280 萬美元，500 萬美元的里程碑，就離開 [670 美元]。為什麼在過去幾個季度的增長之後，情況卻如此平淡？

No. So it was not flat. So I guess when I read through all the components of revenue, when you -- if you add it all together, there is the cost of revenue of [$677], which I guess if you look at the press release in the detail. So to be clear, we had $800,000 in net sales royalties from AZSTARYS. So it was not flat.

不，所以它並不平坦。所以我想，當我通讀收入的所有組成部分時，如果你把它們加在一起，就會有 [677 美元] 的收入成本，如果你詳細查看新聞稿，我想這是。需要明確的是，我們從 AZSTARYS 獲得了 800,000 美元的淨銷售特許權使用費。所以它並不平坦。

Okay. So the net arimoclomol is not $2.8 million. It's a little less or it is $2.8 million, and it kind of can't be $2.8 million.

好的。因此，阿莫洛醇的淨值不是 280 萬美元。少一點或者是 280 萬美元，但又不可能是 280 萬美元。

There is a cost of revenue associated with the milestone. If you remember, we pay a 10% royalty to request it. And so we had to recognize a 10% reduction based on that. That's the difference that you're thinking of.

與里程碑相關的是收入成本。如果您還記得，我們會支付 10% 的版稅來請求它。因此我們必須在此基礎上減少 10%。這就是你所想的差異。

Okay. And I was curious, in your response to the first question, you were talking about the interim IH data to inform a Phase III trial. But I was thinking, why do you even care about that, the final data is a few months away, isn't that vastly more important and informative in the Phase III than what comes at the end of this quarter?

好的。我很好奇，在您對第一個問題的回答中，您談論的是為 III 期試驗提供信息的臨時 IH 數據。但我在想，為什麼你還要關心這個，最終的數據還要幾個月才能出來，第三階段的數據不是比本季度末的數據更重要、信息更豐富嗎？

So actually, no. The whole point of the Phase II trial was to inform the Phase III trial. It's ultimately, this prodrug is a stimulant. And so we know that there's going to be an effect. And so what we wanted to get out of this trial is really those nuances that we'll need to understand as we're preparing for the Phase III trial and preparing the protocol for the Phase III trial.

所以實際上，不。第二階段試驗的全部目的是為第三階段試驗提供信息。最終，這種前藥是一種興奮劑。所以我們知道這將會產生影響。因此，我們希望從這次試驗中得到的實際上是我們在準備 III 期試驗和準備 III 期試驗方案時需要了解的細微差別。

So this -- getting this interim data is going to allow us to kind of refine that Phase III trial move forward with FDA meetings and further preparations for those -- for the Phase III trial while we finish up to Phase II.

因此，獲得這些中期數據將使我們能夠通過 FDA 會議和進一步的準備工作來完善 III 期試驗，同時我們完成 II 期試驗。

Okay. And lastly, I guess it's fair to assume maybe you can say this is your AZSTARYS milestone that they will substantially decrease as a percentage of the sales figure that triggers that. Here, it's a 20% ratio, but that should substantially decrease as we go forward. Is that at least fair to say?

好的。最後，我想可以公平地假設，也許您可​​以說這是您的 AZSTARYS 里程碑，它們佔觸發該事件的銷售數字的百分比將大幅下降。這裡的比例是 20%，但隨著我們的前進，這個比例應該會大幅下降。至少可以這麼說嗎？

I haven't made that statement. So no, I wouldn't say that.

我沒有發表過這樣的聲明。所以不，我不會這麼說。

So they might actually stay fairly in line with that 20% payout kind of ratio?

那麼他們實際上可能會保持與 20% 的支付比率相當一致嗎？

I mean I think that would be a great outcome as it did. And I'd say this just -- I would just remind you that when we went back and had a chance to renegotiate these milestones back in April of '21. We really were looking for a way to pull milestones forward, if you will. And so those ratios are probably a little bit different than what you might think are typical of a market license. So the fact that the first few are in this range I think, speaks to some of those amendments we were able to get agreed to back in that time frame.

我的意思是，我認為這將是一個很好的結果。我想說的是——我只是提醒你們，當我們在 21 年 4 月回去並有機會重新談判這些里程碑時。如果你願意的話，我們確實在尋找一種推動里程碑向前發展的方法。因此，這些比率可能與您認為的典型市場許可比率略有不同。因此，我認為前幾個在這個範圍內的事實說明了我們能夠在該時間範圍內同意支持的一些修正案。

Yes. I mean to have $25 million trigger sales milestone at any time is a pleasant surprise for sure. So you guys really did a good job on the front end of that.

是的。我的意思是，任何時候達到 2500 萬美元觸發銷售里程碑肯定是一個驚喜。所以你們在前端確實做得很好。

And this does conclude the Q&A portion of today's call. I would now like to turn the call back over to Christal Mickle for any additional or closing remarks.

今天電話會議的問答部分到此結束。我現在想將電話轉回給 Christal Mickle，以徵求任何補充或結束語。

Great. Thank you very much. We're excited about our progress in the first half of 2023 and are looking ahead to continue our momentum. As we look forward to the second half and into 2024, we're focused on the following 3 top priorities: First, to resubmit the arimoclomol NDA to the FDA and strengthened key functions and capabilities to support a successful launch of approved. Second, to complete the Phase II trial of idiopathic hypersomnia and prepare to advance KP1077 into a Phase III trial sometime next year. And third, to continue our work to expand our KP1077 program into narcolepsy.

偉大的。非常感謝。我們對 2023 年上半年取得的進展感到興奮，並期待繼續保持這一勢頭。展望下半年和 2024 年，我們將重點關注以下 3 個首要任務：首先，向 FDA 重新提交阿莫洛莫 NDA，並加強關鍵職能和能力，以支持批准的成功上市。其次，完成特發性嗜睡症的II期試驗，並準備明年某個時候將KP1077推進到III期試驗。第三，繼續我們的工作，將我們的 KP1077 項目擴展到發作性睡病。

Corporate development also remains a priority as we actively engage in conversations to potentially acquire new pipeline assets that would be complementary to our portfolio, and that could benefit from the potential application of our prodrug technology.

企業發展仍然是一個優先事項，因為我們積極參與對話，以潛在收購新的管道資產，這些資產將補充我們的產品組合，並可能從我們的前藥技術的潛在應用中受益。

We're building something really special here at Zevra. We have a legacy of drug development success upon which we are expanding our capabilities by adding an innovative patient-first commercial team, which we believe has the potential to drive meaningful value for our shareholders. But not only that, we're fully committed to our mission of bringing much needed therapies to people living with rare disease.

我們正在 Zevra 打造一些非常特別的東西。我們擁有藥物開發成功的傳統，在此基礎上，我們正在通過增加一個以患者為先的創新商業團隊來擴展我們的能力，我們相信該團隊有潛力為我們的股東帶來有意義的價值。不僅如此，我們完全致力於為罕見病患者提供急需的治療方法的使命。

Patients, caregivers, and all of those who are supporting the rare disease communities that we serve are at the forefront of everything that we do. I want to thank our shareholders for your continuing support of our efforts.

患者、護理人員以及所有支持我們所服務的罕見疾病社區的人都處於我們所做的一切的最前沿。我要感謝我們的股東對我們努力的持續支持。

Additionally, I want to give a special thanks to our employees for their energy, enthusiasm and relentless commitment to make Zevra's success. We're excited about the prospects, opportunities and potential for success in front of us. Thank you for joining us today, and we look forward to speaking with you in the future.

此外，我要特別感謝我們的員工，他們的精力、熱情和不懈的努力使 Zevra 取得了成功。我們對眼前的前景、機遇和成功潛力感到興奮。感謝您今天加入我們，我們期待將來與您交談。

This concludes today's Zevra Therapeutics second quarter 2023 earnings call and webcast. You may disconnect your line at this time, and have a wonderful day.

今天的 Zevra Therapeutics 2023 年第二季度財報電話會議和網絡廣播到此結束。此時您可以斷開線路，度過美好的一天。