Zevra Therapeutics Inc (ZVRA) 2022 Q4 法說會逐字稿

Good day, and welcome to the Zevra Therapeutics Fourth Quarter and Full Year 2022 Update Call. (Operator Instructions) Please be advised that today's call is being recorded.

美好的一天，歡迎來到 Zevra Therapeutics 第四季度和 2022 年全年更新電話會議。 （接線員說明）請注意，今天的通話正在錄音中。

I want to hand the call over to Zevra's Vice President of Investor Relations and Corporate Communications, Nichol Ochsner. Thank you. You may begin.

我想把電話轉給 Zevra 的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. Thank you for joining us today to review Zevra's Fourth quarter and full year 2022 clinical operational progress and financial results. A few housekeeping items before we start. I invite you to view the webcast slides and the press release, both of which were issued this morning and can be found in the Investors section of our website.

早上好。感謝您今天加入我們，回顧 Zevra 第四季度和 2022 年全年的臨床運營進展和財務業績。在我們開始之前先做一些清潔用品。我邀請您觀看今天上午發布的網絡廣播幻燈片和新聞稿，可以在我們網站的投資者部分找到。

As outlined on Slide 2, during today's presentation, we will be making several forward-looking statements. These forward-looking statements include, but are not limited to, the clinical and regulatory path for arimoclomol, AZSTARYS, revenue milestones and expected revenue from the French EAP program, the planned next steps in our pipeline programs; the timing for enrollment, initiation, the completion and reporting of data from our clinical trials and the upcoming Annual Meeting of Stockholders. These statements are neither promises nor guarantees and involve risks and uncertainties and other important factors that may cause actual results to differ materially from those discussed here. Important factors that could cause actual results to differ from forward-looking statements can be found in the Risk Factors section of our annual report on Form 10-K for the full year ended December 31, 2022, expected to be filed with the SEC today.

如幻燈片 2 所述，在今天的演示中，我們將發表幾項前瞻性陳述。這些前瞻性陳述包括但不限於 arimoclomol、AZSTARYS 的臨床和監管路徑、法國 EAP 計劃的收入里程碑和預期收入、我們管道計劃中計劃的後續步驟；我們的臨床試驗數據的註冊、啟動、完成和報告時間以及即將召開的股東年會。這些陳述既不是承諾也不是保證，涉及風險和不確定性以及其他可能導致實際結果與此處討論的結果存在重大差異的重要因素。可能導致實際結果與前瞻性陳述不同的重要因素可以在我們截至 2022 年 12 月 31 日全年的 10-K 表格年度報告的風險因素部分找到，預計將於今天向美國證券交易委員會提交。

Finally, you can view the agenda for today's call on Slide 3. I'm pleased to welcome Zevra's management team members participating in today's call. I'm joined today by our CEO, Richard Pascoe, our President and Co-Founder; Dr. Travis Mickle; our Chief Financial Officer; LaDuane Clifton, our Chief Product Development Officer and Co-Founder; Christal Mickle; and Joshua Schafer, Chief Commercial Officer and Executive Vice President, Business Development.

最後，您可以在幻燈片 3 上查看今天電話會議的議程。我很高興地歡迎 Zevra 的管理團隊成員參加今天的電話會議。今天，我們的首席執行官、總裁兼聯合創始人理查德·帕斯科 (Richard Pascoe) 加入了我的行列；特拉維斯·米克爾博士；我們的首席財務官；我們的首席產品開發官兼聯合創始人 LaDuane Clifton；克里斯塔爾·米克爾；首席商務官兼業務發展執行副總裁 Joshua Schafer。

I will now turn the call over to Rich Pascoe.

我現在將把電話轉給 Rich Pascoe。

Thank you, Nichol, and thank you all for joining us today to review our Q4 and full year 2022 results. Before we get into the highlights of the successful year, I want to take a step back and talk about where we are today and provide an overview of our strategic evolution over the past 18 months. A lot has happened with a new name and focus, it is important to walk our investors through how we got here and share my enthusiasm for our future. (inaudible) Zevra Therapeutics, a nimble and focused rare disease company. Our team has a successful track record of success in championing patients in need as well as tackling and overcoming challenges in drug development and regulatory approval.

謝謝 Nichol，也感謝大家今天加入我們，回顧我們的第四季度和 2022 年全年業績。在我們進入成功的一年的亮點之前，我想退後一步，談談我們今天所處的位置，並概述我們過去 18 個月的戰略演變。有了新的名稱和重點，發生了很多事情，重要的是要讓我們的投資者了解我們是如何走到這一步的，並分享我對我們未來的熱情。 （聽不清）Zevra Therapeutics，一家靈活而專注的罕見病公司。我們的團隊在支持有需要的患者以及應對和克服藥物開發和監管審批方面的挑戰方面有著成功的記錄。

We are leveraging our years of expertise and unique insights to chart a new course for drug development and forging pathways to success for promising product candidates. As we move Zevra forward, we will continue to leverage our legacy platform to target internally discovered rare disease product opportunities and extend our pipeline assets exclusivity through life cycle management. In this way, we bring transformational therapies and hope to patients with rare diseases and their families and create value for our shareholders.

我們正在利用我們多年的專業知識和獨特的見解來規劃藥物開發的新課程，並為有前途的候選產品開闢成功之路。隨著我們推動 Zevra 向前發展，我們將繼續利用我們的遺留平台來瞄準內部發現的罕見疾病產品機會，並通過生命週期管理擴展我們的管道資產排他性。通過這種方式，我們為罕見病患者及其家人帶來轉化療法和希望，為我們的股東創造價值。

Importantly, we are well positioned for success, we have a robust pipeline of promising rare disease product candidates with multiple value-creating milestones expected over the coming year. We have a world-class leadership team with the experience of numerous successful product approvals and an equally accomplished Board of Directors that align with our strategic trajectory in rare disease. Supporting it all, we have a strong balance sheet. So how did we get here? We've worked hard to evolve the company's strategy over the past 2 years, thoughtfully led by our management team in collaboration with our Board of Directors and supported by our shareholders.

重要的是，我們為成功做好了充分準備，我們擁有強大的有前途的罕見疾病候選產品管道，預計在來年將實現多個創造價值的里程碑。我們擁有一支世界一流的領導團隊，擁有眾多成功產品批准的經驗，以及一個同樣成就卓著的董事會，與我們在罕見病領域的戰略軌跡保持一致。支持這一切，我們有一個強大的資產負債表。那麼我們是怎麼到這裡的呢？在我們的管理團隊與董事會的合作下，在我們的股東的支持下，我們在過去 2 年中努力發展公司的戰略。

After the approval, licensing and commercialization of AZSTARYS, and our actions to put the company on a firmer financial footing, the management team and Board pause to evaluate where we were and what we learned in getting AZSTARYS to the market. Our objective was to determine our best path forward to create value in a time frame and at a scale that our shareholders deserve. We concluded that we have strong capabilities and success in the scientific, development and regulatory areas. However, focusing exclusively on a pipeline of product candidates that will eventually compete in heavily generic markets and out-licensing those products as a commercial strategy would likely fail to meet our objective of delivering a significant return on investment to our shareholders.

在 AZSTARYS 獲得批准、許可和商業化，以及我們採取行動使公司處於更穩固的財務基礎之後，管理團隊和董事會停下來評估我們在將 AZSTARYS 推向市場的過程中所處的位置和我們學到的東西。我們的目標是確定我們的最佳前進道路，以在我們的股東應得的時間範圍內和規模上創造價值。我們的結論是，我們在科學、發展和監管領域擁有強大的能力和成功。然而，僅專注於最終將在高度仿製藥市場中競爭的一系列候選產品，並將這些產品作為商業策略對外授權可能無法實現我們為股東帶來可觀投資回報的目標。

We then work thoughtfully -- we then work to thoughtfully, set a new course for the company, focusing on bringing the organization's existing strengths together with a refined strategic focus on rare disease indications with the goal of commercializing our products in the United States. We took a series of transformative actions that align perfectly with our strategy, highlighted by the acquisition of arimoclomol an NDA-stage product candidate upon which we intend to build commercial capabilities that will allow Zevra to create value for the benefit of shareholders. This new direction capitalizes on our strengths and cash position to enable us to retain the value of our hard-earned approvals and control our commercial destiny while delivering much needed therapeutics to patients with limited or no treatment options.

然後我們深思熟慮地工作——然後我們深思熟慮地工作，為公司設定新的路線，專注於將組織的現有優勢與對罕見疾病適應症的精細戰略重點結合起來，目標是在美國將我們的產品商業化。我們採取了一系列與我們的戰略完全一致的變革行動，其中突出的是收購了 arimoclomol，這是一種處於 NDA 階段的候選產品，我們打算在此基礎上建立商業能力，使 Zevra 能夠為股東的利益創造價值。這一新方向利用我們的優勢和現金狀況，使我們能夠保留我們來之不易的批准的價值並控制我們的商業命運，同時為治療選擇有限或沒有治療選擇的患者提供急需的治療。

It is important to note that rare disease is not an entirely new focus for us. We were already working in rare disease with our prodrug technology applied in rare sleep disorders with KP1077 for idiopathic hypersomnia. From that experience, we recognize that rare disease drug development offers several significant advantages over development in large mass market indications.

值得注意的是，罕見病對我們來說並不是一個全新的關注點。我們已經在研究罕見疾病，我們的前藥技術應用於罕見睡眠障礙，KP1077 用於治療特發性嗜睡症。從那次經驗中，我們認識到罕見病藥物開發與大規模市場適應症的開發相比具有幾個顯著優勢。

First and foremost, we have the privilege of partnering with patients, families and advocacy groups to deeply understand their needs and ensure that our therapeutic approaches are answering their biggest quality of life and disease management concerns. This ensures our products are relevant and capable of commercial success.

首先，我們有幸與患者、家屬和倡導團體合作，深入了解他們的需求，並確保我們的治療方法能夠解決他們最大的生活質量和疾病管理問題。這確保了我們的產品具有相關性並能夠取得商業成功。

Rare disease drug development time lines are often shorter and involve much smaller studies than larger indications resulting in lower cost of research and development. Through the Orphan Drug Act, the company benefits from incentives, such as priority review voucher and a 6-month review window for pursuing therapeutics for rare diseases and the resulting products receive extended patent protection for longer market exclusivity.

與較大的適應症相比，罕見病藥物的開發時間線通常更短並且涉及的研究規模小得多，從而降低了研發成本。通過《孤兒藥法》，公司受益於優先審評憑證和 6 個月的審評窗口等激勵措施，以尋求罕見疾病的治療方法，由此產生的產品獲得延長的專利保護，以獲得更長的市場獨占性。

Rare Disease products also do not experience significant generic competition once patents expire. Moreover, with a small patient population treated primarily by specialist clinicians, we can bring those products to commercialization with our own in-house commercial team.

一旦專利到期，罕見病產品也不會經歷重大的仿製藥競爭。此外，由於主要由專業臨床醫生治療的患者人數較少，我們可以通過我們自己的內部商業團隊將這些產品商業化。

Taking this together, we saw that rare disease drug development creates an ideal platform for maximizing value creation for patients and shareholders. This led to our decision to focus exclusively on rare disease and our strategic acquisition of arimoclomol. Through that acquisition, we acquired a high potential product candidate for Niemann-Pick disease Type C. We also onboarded an amazing European team with deep connections to the NPC patient community and significant rare disease drug development expertise. As we began focusing on rare diseases, we recognize that our name and branding is KemPharm no longer reflected who we are as a company. So we underwent a process to redefine our messaging and brand story. The outcome of that process is our new name, Zevra Therapeutics and branding to reflect our commitment to the rare disease patients we deserve.

綜上所述，我們看到罕見病藥物開發為最大限度地為患者和股東創造價值創造了一個理想的平台。這導致我們決定專注於罕見疾病和我們對 arimoclomol 的戰略收購。通過那次收購，我們獲得了尼曼匹克病 C 型的高潛力候選產品。我們還聘請了一支與 NPC 患者社區有著深厚聯繫並擁有重要罕見病藥物開發專業知識的出色歐洲團隊。當我們開始關注罕見疾病時，我們認識到我們的名稱和品牌 KemPharm 不再反映我們作為一家公司的身份。因此，我們經歷了一個重新定義我們的信息和品牌故事的過程。這一過程的結果是我們的新名稱 Zevra Therapeutics 和品牌，以反映我們對我們應得的罕見病患者的承諾。

The word Zevra is Greek for zebra, which is the internationally recognized symbol for rare disease community. Interestingly, a group of Zevra is also called (inaudible), these expressions capture our team perfectly as we are [sells] about empowering people with rare diseases. We are confident that Zevra is a name that will resonate with patients, and we envision a dazzling future for the rare disease communities that we serve.

Zevra一詞在希臘語中是斑馬的意思，是國際公認的罕見病群落的象徵。有趣的是，一群 Zevra 也被稱為（聽不清），這些表達完美地抓住了我們的團隊，因為我們正在 [銷售] 為患有罕見疾病的人提供支持。我們相信 Zevra 是一個會引起患者共鳴的名字，我們為我們所服務的罕見病社區設想了一個令人眼花繚亂的未來。

Zevra is better positioned today than at any point in its history as we work towards our key priorities to secure regulatory approval for our pipeline assets, build top-tier commercial capabilities, and enhance our pipeline through internal and external efforts. We have two very strong product candidates with multiple value-creating milestones expected this year. We continue to explore new product opportunities both through our prodrug platform and business development activities focused on rare disease. We are a rare beast in that we already have a growing revenue stream as a development stage company, which bolsters our already strong financial position.

Zevra 今天比其歷史上任何時候都處於更好的位置，因為我們致力於我們的關鍵優先事項，以確保對我們的管道資產獲得監管批准，建立頂級商業能力，並通過內部和外部的努力增強我們的管道。我們有兩個非常強大的候選產品，預計今年將實現多個創造價值的里程碑。我們繼續通過我們的前藥平台和專注於罕見病的業務開發活動探索新的產品機會。我們是一隻罕見的野獸，因為作為一家處於發展階段的公司，我們已經擁有不斷增長的收入來源，這鞏固了我們本已強大的財務狀況。

I am confident in the team and our strong financial foundation and diverse portfolio of multiple clinical programs and in our ability to deliver value in 2023 and beyond. Importantly, we have a fully engaged and supportive Board of Directors that has been deeply involved in our strategic evolution and can help us to advance our company. 2022 was a pivotal year for our organization and our evolution into a rare disease company with the acquisition of arimoclomol and the completion of a 4-year safety study of that product candidate in NPC. Our ongoing collaborative dialogue with the FDA around the program has been highly productive in preparing us for NDA resubmission.

我對團隊和我們強大的財務基礎以及多個臨床項目的多樣化組合以及我們在 2023 年及以後實現價值的能力充滿信心。重要的是，我們有一個充分參與和支持的董事會，他們深入參與了我們的戰略發展，可以幫助我們推動公司發展。 2022 年是我們組織的關鍵一年，也是我們通過收購 arimoclomol 並在 NPC 完成了該候選產品為期 4 年的安全性研究而發展成為一家罕見病公司的關鍵一年。我們與 FDA 圍繞該計劃進行的持續合作對話在我們為重新提交 NDA 做準備方面非常有成效。

We've also made tremendous headway in our KP1077 program for rare sleep disorders over the last year, including positive data from our cardiovascular trial of SDX, a primary component of KP1077 in a Phase II trial initiation in idiopathic hypersomnia. Orphan drug designation for this product candidate in IH provides the advantages I highlighted earlier, including regulatory incentives and extended market exclusivity after approval.

去年，我們在治療罕見睡眠障礙的 KP1077 項目中也取得了巨大進展，包括來自 SDX 心血管試驗的積極數據，SDX 是 KP1077 在特發性嗜睡症 II 期試驗啟動中的主要組成部分。 IH 中該候選產品的孤兒藥指定提供了我之前強調的優勢，包括監管激勵和批准後延長的市場獨占性。

We continue to bolster our strong financial position, earning a onetime fee of nearly $2 million from Corium following the FDA approval of ADLARITY. Our net revenue for the full year was $10.5 million. Cash, cash equivalents and investments as of December 31, 2022, were $102.9 million. Our available capital is expected to extend our cash runway into 2026, an enviable position for any biotech company in today's capital markets.

我們繼續鞏固我們強大的財務狀況，在 FDA 批准 ADLARITY 後，從 Corium 獲得了近 200 萬美元的一次性費用。我們全年的淨收入為 1050 萬美元。截至 2022 年 12 月 31 日，現金、現金等價物和投資為 1.029 億美元。我們的可用資金預計會將我們的現金跑道延長至 2026 年，這對於當今資本市場上的任何生物技術公司來說都是令人羨慕的地位。

In 2022, we began our efforts to further build our team by appointing Nichol Ochsner, as VP of Investor Relations and Corporate Communications. In addition, the Board appointed Christopher Posner as an independent director, another great addition to the team. As you can see from this slide, we've had tremendous momentum in the fourth quarter of 2022 and the beginning of 2023 on several fronts. I want to point out a few of those. Notably, a recent development in the arimoclomol program was the presentation of the data from the interim analysis of the Phase II/III 4-year safety study at the 2023 WORLDSymposium. These data, which demonstrate the clinical benefit of arimoclomol will be a cornerstone of our resubmission of a new drug application expected as early as the third quarter of this year.

2022 年，我們開始努力進一步建設我們的團隊，任命 Nichol Ochsner 為投資者關係和企業傳播副總裁。此外，董事會任命 Christopher Posner 為獨立董事，這是對團隊的又一重要補充。正如您從這張幻燈片中看到的那樣，我們在 2022 年第四季度和 2023 年初在多個方面取得了巨大的發展勢頭。我想指出其中的一些。值得注意的是，arimoclomol 計劃的最新進展是在 2023 年 WORLDSymposium 上展示了 II/III 期 4 年安全性研究的中期分析數據。這些數據證明了 arimoclomol 的臨床益處，將成為我們重新提交新藥申請的基石，預計最早將於今年第三季度提交。

Notably, the data suggests that arimoclomol may reduce the progression of NPC. This underscores our understanding that if you can improve lysosomal function, you can improve outcomes for patients. We also underwent our strategic rebrand to Zevra Therapeutics in alignment with our identity as a rare disease company and to further engage with the rare disease community we joined, the NORD Corporate Counsel.

值得注意的是，數據表明 arimoclomol 可能會減緩 NPC 的進展。這強調了我們的理解，即如果可以改善溶酶體功能，就可以改善患者的預後。我們還對 Zevra Therapeutics 進行了戰略重塑，以符合我們作為罕見病公司的身份，並進一步與我們加入的罕見病社區 NORD 公司顧問進行互動。

Since the beginning of the year, we have made several additional key appointments and changes to our leadership and Board of Directors, strengthening a team that I'm confident can lead Zevra into the future with success. Shown here are our executive team and our Board of Directors, not only are we an accomplished group of decades of experience in R&D and commercialization leadership, but we are also a blend of legacy team members and new talent with skills that can take us into the future. The team is aligned with our direction and transformation into a rare disease company.

自今年年初以來，我們對我們的領導層和董事會進行了數次額外的重要任命和變動，加強了我相信可以帶領 Zevra 成功走向未來的團隊。這裡顯示的是我們的執行團隊和我們的董事會，我們不僅是一個在研發和商業化領導方面擁有數十年經驗的成功團隊，而且我們也是傳統團隊成員和新人才的混合體，他們的技能可以讓我們進入未來。該團隊與我們的方向和轉型為一家罕見疾病公司的方向一致。

Now I'd like to turn our attention to our arimoclomol program for Niemann-Pick Disease Type C. Arimoclomol is administered orally and is formulated for ease of use in varying patient circumstances. This product candidate has been studied in 10 Phase I, 4 Phase II and 3 pivotal Phase II/III trials. Arimoclomol has received orphan drug designation for NPC in the United States and the European Union and Fast Track designation, breakthrough therapy designation and rare pediatric disease designation from the FDA for NPC. If approved in the U.S., arimoclomol would also be eligible to receive a pediatric priority review voucher.

現在，我想將注意力轉移到我們針對 C 型尼曼匹克病的 arimoclomol 計劃。Arimoclomol 是口服給藥，其配方易於在不同的患者情況下使用。該候選產品已在 10 個 I 期、4 個 II 期和 3 個關鍵的 II/III 期試驗中進行了研究。 Arimoclomol 已獲得美國和歐盟針對 NPC 的孤兒藥指定，以及 FDA 對 NPC 的快速通道指定、突破性治療指定和罕見兒科疾病指定。如果在美國獲得批准，arimoclomol 也將有資格獲得兒科優先審查憑證。

We are on track to submit the new drug application to the FDA as early as the third quarter of this year for arimoclomol. One of the most attractive aspects of the arimoclomol program is that it should it be approved, we have the near-term opportunity to commercialize the product ourselves to retain the full market value for our shareholders.

我們有望最早在今年第三季度向 FDA 提交 arimoclomol 的新藥申請。 arimoclomol 計劃最吸引人的方面之一是，如果它獲得批准，我們將有機會在短期內自行將該產品商業化，從而為我們的股東保留全部市場價值。

We believe a small and nimble commercial team could fully serve the specialists and medical centers treating the NPC patient population. The benefit of a small commercial team is the lower cost of market entry. We believe that our established and new advocacy relationships in the NPC community will help support the adoption of arimoclomol, and we have already established market entry with this patient population through our U.S. and EU early access programs. Beyond our immediate focus on a successful U.S. commercial launch, we also see the commercial potential for arimoclomol outside of the U.S., in the EU, Japan, China and other geographies.

我們相信，一個小型而靈活的商業團隊可以為治療 NPC 患者群體的專家和醫療中心提供全面服務。小型商業團隊的好處是進入市場的成本較低。我們相信，我們在 NPC 社區中建立的和新的宣傳關係將有助於支持 arimoclomol 的採用，並且我們已經通過我們的美國和歐盟早期訪問計劃與這些患者群體建立了市場准入。除了我們當前關注的是在美國成功上市外，我們還看到了 arimoclomol 在美國以外、歐盟、日本、中國和其他地區的商業潛力。

Now I will highlight our KP1077 program for rare sleep disorders, beginning with idiopathic hypersomnia, which is currently enrolling patients and dosing patients in a Phase II clinical study in the U.S. The market potential for idiopathic hypersomnia is also highly compelling with limited treatment options available for this small underserved patient segment. KP1077 has been designated by the FDA as an orphan drug as well as possible eligibility for fast-track review status and designation as a breakthrough treatment.

現在我將重點介紹我們針對罕見睡眠障礙的 KP1077 計劃，從特發性嗜睡開始，該項目目前正在美國的 II 期臨床研究中招募患者並給患者給藥。這個服務不足的小患者群體。 KP1077已被 FDA 指定為孤兒藥，並可能符合快速審查狀態和指定為突破性治療的資格。

In addition, we believe that a differentiated from other treatment options, pricing KP1077 in between products like Teva Pharmaceuticals' PROVIGIL, which is approximately a $24,000 per year treatment at the highest dose, and Jazz Pharmaceuticals' Xywav, which is approximately $187,000 per year at the highest dose that leads to capture -- capturing significant market share. Because this is a rare indication, our intent is the commercialization of this product ourselves, which is aligned with our strategy for arimoclomol and therefore, allows us to keep a larger portion of the economic value.

此外，我們認為，與其他治療方案不同，KP1077 的定價介於 Teva Pharmaceuticals 的 PROVIGIL 和 Jazz Pharmaceuticals 的 Xywav 等產品之間，前者在最高劑量下每年治療費用約為 24,000 美元，後者約為每年 187,000 美元導致捕獲的最高劑量 -- 捕獲顯著的市場份額。因為這是一個罕見的跡象，我們的目的是自己將該產品商業化，這與我們的 arimoclomol 戰略一致，因此使我們能夠保留更大一部分的經濟價值。

We expect interim data from Phase II -- from the Phase II trial of KP1077 in idiopathic hypersomnia by the third quarter of this year and top line data by the end of 2023. Importantly, the interim data will also be an open-label titration phase, which is meaningful because it will allow us to start designing the Phase III study in IH. We are also planning a development program for KP1077 in narcolepsy. The IND filing for this additional program is expected during the second quarter of 2023.

我們預計來自 II 期的中期數據——來自今年第三季度 KP1077 治療特發性嗜睡症的 II 期試驗和 2023 年底的一線數據。重要的是，中期數據也將是一個開放標籤滴定階段，這很有意義，因為它將允許我們開始設計 IH 的 III 期研究。我們還計劃針對發作性睡病的 KP1077 開發計劃。該附加項目的 IND 申請預計在 2023 年第二季度提交。

With that, I will turn the call over to our CFO, LaDuane Clifton. LaDuane?

有了這個，我將把電話轉給我們的首席財務官 LaDuane Clifton。拉杜安？

Thank you, Rich, and good morning, everyone. Let's jump right into the numbers with an update on the commercial progress of AZSTARYS. Like many of you, we closely track the prescription trends for AZSTARYS and the trend line since the third quarter of last year has become more encouraging. While the early days of the launch were impacted by COVID-related challenges, and the need for greater formulary coverage with the largest PBMs, there has been a meaningful change in prescription volumes starting in July of 2022. You may recall that we had reported to you that as of Q3 2022, Corium had achieved coverage with the three largest PBMs and double the size of their field force to 175 reps.

謝謝你，里奇，大家早上好。讓我們直接進入數字，了解 AZSTARYS 商業進展的最新情況。像你們中的許多人一樣，我們密切跟踪 AZSTARYS 的處方趨勢，自去年第三季度以來趨勢線變得更加令人鼓舞。雖然發布的早期受到 COVID 相關挑戰的影響，以及最大 PBM 需要更大的處方覆蓋範圍，但從 2022 年 7 月開始處方量發生了有意義的變化。您可能還記得我們曾向你知道截至 2022 年第三季度，Corium 已經實現了三個最大的 PBM 的覆蓋範圍，並將其現場力量的規模增加了一倍，達到 175 個代表。

The growth trajectory of the product since that time has continued, and we are optimistic about the possibility of reaching one or more milestones during 2023. With an improving prescription trend, the amount of the royalties realized from the license is meaningful, though modest. The table provided here shows actual royalties earned by quarter and the corresponding prescription count estimates based on publicly available data. These trends suggest that royalties will contribute more revenue in the future. Still, we realize that achieving the sales milestones may be a more significant driver of value from this license. This leads to another critical point. Our legacy model for developing an asset and then out-license for commercialization is not expected to drive strong growth for Zevra in the short or medium term.

該產品自那時以來的增長軌跡一直在延續，我們對在 2023 年達到一個或多個里程碑的可能性持樂觀態度。隨著處方趨勢的改善，從許可中實現的特許權使用費數額雖然不大，但意義重大。此處提供的表格顯示了按季度賺取的實際特許權使用費以及根據公開數據估計的相應處方藥數量。這些趨勢表明，特許權使用費將在未來貢獻更多收入。儘管如此，我們意識到實現銷售里程碑可能是該許可帶來的更重要的價值驅動力。這導致了另一個臨界點。我們開發資產然後授權商業化的傳統模式預計不會在短期或中期推動 Zevra 的強勁增長。

Back in 2021, as we began thinking strategically about rebuilding our pipeline, we knew this had to be addressed. The ability to directly commercialize a product we develop and get approved became a primary criterion in evaluating where we would focus our pipeline investments.

早在 2021 年，當我們開始從戰略上考慮重建管道時，我們知道必須解決這個問題。將我們開發並獲得批准的產品直接商業化的能力成為評估我們將重點關注管道投資的主要標準。

Our decision to focus on the rare disease space positions us to field a small, nimble commercial team that can be highly effective and drive better return on capital than the results we have had to date with the out-licensed model. We see the AZSTARYS as foundational to where we are as a company but we also look forward to the potential for growth that we may be able to unlock with the direct commercialization of both arimoclomol and KP1077, if approved.

我們決定專注於罕見疾病領域，這使我們能夠組建一支小型、靈活的商業團隊，該團隊可以非常有效地推動資本回報，而不是我們迄今為止使用外授權模式所獲得的結果。我們將 AZSTARYS 視為我們作為一家公司的基礎，但我們也期待著如果獲得批准，我們可以通過 arimoclomol 和 KP1077 的直接商業化釋放增長潛力。

Now let's focus on the financial results for Q4 and full year 2022. In 2022, we took significant steps to improve our financial position. We continue to have a solid balance sheet and adding the arimoclomol program has begun to provide a steady revenue stream to support our ongoing regulatory and product development initiatives. For Q4, net revenue was $2.3 million, driven primarily by reimbursements from the French EAP program.

現在讓我們關注第四季度和 2022 年全年的財務業績。2022 年，我們採取了重大措施來改善我們的財務狀況。我們繼續擁有穩健的資產負債表，並且添加 arimoclomol 計劃已經開始提供穩定的收入來源，以支持我們正在進行的監管和產品開發計劃。第四季度，淨收入為 230 萬美元，主要受法國 EAP 計劃的報銷推動。

Full year net revenue was $10.5 million. We reported a Q4 net loss of $9 million or $0.26 per share, which was driven by our R&D investments and increased G&A, all associated with the KP1077 and arimoclomol programs. For the full year, net loss was $41.5 million or $1.20 per share, which includes a onetime noncash charge of $17.7 million related to the in-process R&D assets we acquired from Orphazyme.

全年淨收入為 1050 萬美元。我們報告第四季度淨虧損 900 萬美元或每股 0.26 美元，這是由我們的研發投資和增加的 G&A 推動的，所有這些都與 KP1077 和 arimoclomol 計劃有關。全年淨虧損為 4150 萬美元或每股 1.20 美元，其中包括與我們從 Orphazyme 收購的正在進行的研發資產相關的一次性非現金費用 1770 萬美元。

On a non-GAAP basis, FY 2022 net loss, excluding the onetime noncash charge was $23.9 million or $0.69 per basic and diluted share. And as Rich has already noted, our cash position remains solid with $102.9 million on the balance sheet as of December 31, 2022. Looking ahead to 2023, we reiterate our guidance that our existing available capital on the balance sheet is expected to extend our cash runway into 2026. This includes the reimbursement from the French EAP, what we need for the arimoclomol NDA resubmission, the completion of the development program for KP1077 through its NDA submission and potential PDUFA as well as our preparations for the possible U.S. launch of arimoclomol if approved.

按非公認會計原則計算，2022 財年扣除一次性非現金費用後的淨虧損為 2390 萬美元，即每股基本股和稀釋股 0.69 美元。正如 Rich 已經指出的那樣，截至 2022 年 12 月 31 日，我們的現金狀況仍然穩固，資產負債表上為 1.029 億美元。展望 2023 年，我們重申我們的指導意見，即我們資產負債表上的現有可用資本預計將擴大我們的現金到 2026 年的跑道。這包括法國 EAP 的報銷，我們重新提交 arimoclomol NDA 所需的條件，通過提交 NDA 和潛在的 PDUFA 完成 KP1077 的開發計劃，以及我們為美國可能推出 arimoclomol 所做的準備，如果得到正式認可的。

In addition, we anticipate that the prescription trend for AZSTARYS will allow us to earn at least one and possibly two of the sales milestones under that license agreement during 2023. Net revenue from the French EAP program is expected to continue at the rate of about $2 million per quarter throughout the year.

此外，我們預計 AZSTARYS 的處方藥趨勢將使我們能夠在 2023 年根據該許可協議獲得至少一個甚至兩個銷售里程碑。法國 EAP 計劃的淨收入預計將繼續保持在 2 美元左右的速度全年每季度百萬。

To conclude, we believe we are in a solid financial position with numerous opportunities to create value for our shareholders as we execute our business plans. And now I'll return the call back to Rich.

總而言之，我們相信我們的財務狀況穩固，在執行業務計劃時有許多機會為股東創造價值。現在我會把電話回給 Rich。

Thank you, LaDuane. As we look to 2023, I'm excited about what lies ahead as we continue to transform Zevra and work to enhance value creation for our shareholders. We continue our ongoing discussions with regulatory agencies and are preparing to refile the arimoclomol new drug application as soon as the third quarter of this year.

謝謝你，拉杜安。展望 2023 年，我對未來的前景感到興奮，因為我們將繼續改造 Zevra 並努力為股東創造更高的價值。我們繼續與監管機構進行持續的討論，並準備最快在今年第三季度重新提交 arimoclomol 新藥申請。

For the KP1077 program in rare sleep disorders, we are on track to file an IND for 1077 in narcolepsy in the second quarter of this year, and we also anticipate interim data from the Phase II trial in idiopathic hypersomnia, as early as the third quarter, with top line results in that trial by the time -- by the end of this year. Those data have the potential to not just support the advancement of KP1077 into a Phase III study in IH but also may support a Phase III trial in narcolepsy. We anticipate ongoing revenue from our arimoclomol expanded access program in France and we have the potential to realize additional sales milestones and revenue for AZSTARYS.

對於治療罕見睡眠障礙的 KP1077 項目，我們有望在今年第二季度提交 1077 治療發作性睡病的 IND，我們還預計最早將於第三季度獲得特發性嗜睡症 II 期試驗的中期數據，到今年年底，該試驗的最高結果。這些數據不僅有可能支持將 KP1077 推進 IH 的 III 期研究，而且還可能支持發作性睡病的 III 期試驗。我們預計我們在法國的 arimoclomol 擴展訪問計劃將持續帶來收入，我們有可能為 AZSTARYS 實現額外的銷售里程碑和收入。

This provides further capital flexibility and the potential to further extend our cash runway, which already extends into 2026. In closing, I want to reiterate our commitment to creating value for our shareholders and bringing life-enhancing products to patients suffering from rare diseases.

這提供了進一步的資本靈活性，並有可能進一步延長我們的現金跑道，該跑道已經延伸到 2026 年。最後，我想重申我們為股東創造價值並為患有罕見疾病的患者提供改善生活的產品的承諾。

As I look around our industry, I see small-cap biotech companies dealing with failed clinical programs, employee layoffs, toxic financings and bankruptcies among other challenges. In contrast, Zevra is financially sound with two promising late-stage assets, and we are growing the company in a thoughtful and measured fashion.

當我環顧我們的行業時，我看到小型生物技術公司正在應對臨床項目失敗、員工裁員、有毒融資和破產等挑戰。相比之下，Zevra 的財務狀況良好，擁有兩項有前途的後期資產，而且我們正在以深思熟慮和慎重的方式發展公司。

Before we open the call for questions, I want to briefly address the alternative slate of 3 director candidates proposed by 1 of our shareholders. Zevra Board believes that electing any of these candidates would diminish the overall quality of and experience represented on the Board.

在我們開始提問之前，我想簡要介紹一下我們的一位股東提出的 3 位董事候選人的備選名單。 Zevra 董事會認為，選舉這些候選人中的任何一個都會降低董事會的整體素質和經驗。

By contrast, the 3 incumbent directors collectively bring decades of biotech and pharmaceutical experiences both the senior executives and as public company Board members. Their backgrounds cover a range of relevant areas, including drug development, medical, finance, business development and commercialization, all of which are essential to driving continued momentum and shareholder value as we execute our transformative growth strategy.

相比之下，三位現任董事共同帶來了數十年的生物技術和製藥經驗，包括高級管理人員和上市公司董事會成員。他們的背景涵蓋一系列相關領域，包括藥物開發、醫療、金融、業務發展和商業化，所有這些對於我們執行轉型增長戰略時推動持續發展勢頭和股東價值至關重要。

Your Board regularly seeks to maintain open communication with our shareholders and values constructive input. In fact, many of the changes I discussed on this call today are in direct response to feedback received from our shareholders. We heard you loud and clear that you want to change that you value revenue and that you wanted the Board and management to be bold. We heated that call. We took a hard look at our organizational strengths, we invested in a better understanding of where and how to invest the resources entrusted to us by our shareholders.

您的董事會定期尋求與我們的股東保持開放的溝通，並重視建設性意見。事實上，我今天在電話會議上討論的許多變化都是對股東反饋的直接回應。我們清楚地聽到您想要改變，您重視收入，並且希望董事會和管理層大膽。我們加熱了那個電話。我們仔細審視了我們的組織優勢，我們投資於更好地了解股東委託給我們的資源的投資地點和方式。

We continue to leverage the team that got us to higher ground, and we added new talent where needed. We undertook an ongoing Board refreshment program to bring new and critical thinking to the boardroom, and we focused on creating value to the commercialization of rare novel disease products in areas of significant unmet need.

我們繼續利用讓我們取得更高成就的團隊，並在需要時增加新的人才。我們進行了一項持續的董事會更新計劃，為董事會帶來新的和批判性的思維，我們專注於在重大未滿足需求的領域為罕見的新型疾病產品的商業化創造價值。

I believe that today, the company is in the strongest position to succeed at any time in its history. And I'm so excited for our future as a company and what we aim to accomplish for patients and shareholders alike. Thank you for your continued support as we work to transform lives with new therapies for rare diseases with limited or no treatment options.

我相信，今天，公司正處於其歷史上任何時候取得成功的最有利地位。我對我們作為一家公司的未來以及我們為患者和股東實現的目標感到非常興奮。感謝您一直以來的支持，因為我們致力於通過治療方案有限或沒有治療方案的罕見疾病的新療法來改變人們的生活。

Please note that we will not be commenting further on the proxy matter during the Q&A, and I would appreciate it if you would keep your questions directed to our performance, results and strategy.

請注意，我們不會在問答環節進一步評論代理事宜，如果您將問題直接針對我們的業績、結果和戰略，我將不勝感激。

With that, I will now return the call to the operator for questions. Operator?

有了這個，我現在將把電話返回給接線員詢問問題。操作員？

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

（操作員說明）我們的第一個問題來自 Canaccord Genuity 的 Sumant Kulkarni。

This is Kyle speaking for Sumant Kulkarni. Two questions from us. Has there been any specific interactions with the FDA since your last update that gives you more confidence and your ability to potentially refile the arimoclomol NDA as early as 3Q?

我是 Kyle 代表 Sumant Kulkarni 發言。我們有兩個問題。自上次更新以來，是否與 FDA 有任何具體的互動，讓您更有信心並有能力最早在第 3 季度重新提交 arimoclomol NDA？

And then the second question, has the FDA already seeing the open-label extension data presented recently -- if not, when do you expect the agency to see that data? Would it be prior to the filing or as part of the buying packaging?

然後是第二個問題，FDA 是否已經看到最近提供的開放標籤擴展數據——如果沒有，您希望該機構何時看到該數據？是在備案之前還是作為購買包裝的一部分？

Kyle, it's Rich. Thanks for the question. I'm going to ask Travis Mickle to address those questions.

凱爾，它很豐富。謝謝你的問題。我要請 Travis Mickle 來解決這些問題。

Yes, sure. No problem. So as far from our last update, we have not had a more formal interaction with the FDA as to the resubmission. And then which really answers the next part of your question as well, which is, no, the FDA hasn't seen the data yet. We do plan to submit the information, the ongoing clinical data, the 4-year wrap-up study as well as additional confirmatory evidence that was collected, and we will either provide that to them in a form of a formal meeting or we will actually just provide that to them and ask questions. So the format of that in our ongoing dialogue hasn't been decided yet, but we will update as soon as we have any new information.

是的，當然。沒問題。因此，自我們上次更新以來，我們還沒有與 FDA 就重新提交進行更正式的互動。然後這也真正回答了你問題的下一部分，不，FDA 還沒有看到數據。我們確實計劃提交信息、正在進行的臨床數據、4 年總結研究以及收集到的其他確認證據，我們將以正式會議的形式提供給他們，或者我們將實際只需將其提供給他們並提出問題即可。因此，我們正在進行的對話的形式尚未確定，但我們會在獲得任何新信息後立即更新。

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。

What sales threshold trigger that first and second AZSTARYS milestone, and I think they are $10 million and $20 million each, if I remember correctly. When in 2023, do you think you would intend to achieve those two sales thresholds that would trigger the $10 million and the $20 million?

什麼銷售門檻觸發了 AZSTARYS 的第一個和第二個里程碑，如果我沒記錯的話，我認為它們分別是 1000 萬美元和 2000 萬美元。到 2023 年時，您認為您會打算達到觸發 1000 萬美元和 2000 萬美元的這兩個銷售門檻嗎？

Yes. Jonathan, thank you for the questions. So while we've tried to provide more information today than we have in the past from publicly available data, we're still not able to give the exact sales thresholds or the actual amount of the milestones. So with that said, we do expect likely if we achieve 1 or [costly] 2 of those, it would most likely be toward the second half of 2023.

是的。喬納森，謝謝你的提問。因此，儘管我們今天試圖通過公開數據提供比過去更多的信息，但我們仍然無法給出確切的銷售門檻或里程碑的實際數量。因此，話雖如此，我們確實預計，如果我們實現其中的 1 個或 [代價高昂的] 2 個，那很可能會在 2023 年下半年實現。

And Jonathan, it's Rich. I might just add, the way that deal is constructed, which is good for the company, they were lower thresholds than you might typically find in a license agreement for the achievement of certain milestones. And so we try to front-load as much of it as we could with respect to those types of outcomes. And so I think -- it's why, in large part, we're very optimistic that we'll hit one perhaps more than one this year.

喬納森，它很豐富。我可能只是補充說，交易的構建方式對公司有利，它們的門檻低於您通常在許可協議中找到的實現某些里程碑的門檻。因此，我們嘗試盡可能多地提前加載這些類型的結果。所以我認為——這就是為什麼在很大程度上，我們非常樂觀地認為我們今年會達到一個以上。

Okay. You mentioned narcolepsy once in the press release. So will you be waiting for the outcome in IH before starting perhaps a Phase III trial in narcolepsy or are you still going to start a Phase II/III trial before getting any data in IH?

好的。你在新聞稿中提到過發作性睡病。那麼，在開始嗜睡症的 III 期試驗之前，您是否會等待 IH 的結果，或者在獲得 IH 的任何數據之前，您是否仍將開始 II/III 期試驗？

So this is Christal Mickle. We are actually -- we will look to see what data we get from this Phase II study with IH and determine whether or not we go with the parallel program with narcolepsy and IH for a Phase III study that would help with enrollment and other cost savings there. But again, we will wait for the readout with the Phase II study before we make any of those decisions.

這是 Christal Mickle。我們實際上 - 我們將看看我們從 IH 的 II 期研究中獲得了什麼數據，並確定我們是否與發作性睡病和 IH 的平行計劃一起進行 III 期研究，這將有助於註冊和其他成本節省那裡。但同樣，在我們做出任何這些決定之前，我們將等待 II 期研究的讀數。

Okay. And I'm guessing just briefly the arimoclomol 4Q data. I mean 4Q revenue was about $1.9 million? Or was there a bunch of other nondrug revenue in there?

好的。我只是簡單地猜測 arimoclomol 4Q 數據。我的意思是第 4 季度的收入約為 190 萬美元？或者那裡有一堆其他非藥物收入？

No, that's right, Jonathan. That was (inaudible). And just keep in mind that, that includes this clawback liability that we have to record. So we often talk about gross revenue of $1 million a month from that for about [EUR 1 million] a month. And then we have to clawback the liability. I think you may be familiar with that from prior quarters.

不，是的，喬納森。那是（聽不清）。請記住，這包括我們必須記錄的追回責任。因此，我們經常談論每月 100 萬美元的總收入，而每月的總收入約為 [100 萬歐元]。然後我們必須收回責任。我想你可能對前幾個季度的情況很熟悉。

(Operator Instructions) Our next question comes from Louise Chen with Cantor Fitzgerald.

（操作員說明）我們的下一個問題來自 Louise Chen 和 Cantor Fitzgerald。

Congratulations on all the progress this quarter. So I have two questions for you. I wanted to ask you about IH and the readouts that are coming, the interim and then the top line data readout later this year? And what would you consider a successful outcome that would make you competitive in the market?

祝賀本季度取得的所有進展。所以我有兩個問題要問你。我想問你關於 IH 和即將到來的讀數，今年晚些時候的中期和頂線數據讀數？您認為什麼是能讓您在市場上具有競爭力的成功結果？

And then also, the other question I have for you is when you think about expanding your rare disease pipeline, are you going to do that through M&A, internal development? What kind of resources can you put behind it? And when could we see additional products being added? I know you're very busy with what you have on your plate right now, but just kind of curious, thinking longer term?

然後，我要問你的另一個問題是，當你考慮擴大你的罕見病管道時，你會通過併購、內部開發來實現嗎？你可以在背後投入什麼樣的資源？我們什麼時候可以看到添加更多產品？我知道你現在正忙著處理你盤子裡的東西，但只是有點好奇，從長遠考慮？

So this is Christal Mickle to answer your first question. With the interim data, we're really looking at a number of things such as do we have the right amount of patients to power a study in a future study and really looking at what a future study would look like, dosing regimen things like that. So those are all still playing out. Obviously, we expect with our [FDA profile], looking different than saying what's on the market as far as off-label use of methylphenidate and things like that. We look to that as a differentiator with our product as we have with the start in the past.

我是 Christal Mickle 來回答你的第一個問題。有了中期數據，我們真的在研究很多事情，比如我們是否有合適數量的患者來為未來的研究提供動力，真正在研究未來的研究會是什麼樣子，給藥方案之類的.所以這些都還在發揮作用。顯然，我們希望我們的 [FDA 簡介] 看起來與市場上關於哌醋甲酯的標籤外使用等類似情況的說法不同。我們將其視為我們產品的差異化因素，就像我們過去的開始一樣。

This is Joshua Schafer. I'll take the second question. We are very actively looking to add new products to the portfolio, whether that would be through internal development and leveraging our prodrug platform to bring new products into the pipeline. But we're also looking very actively at potential M&A licensing deals, any number of constructs to bring additional products into our portfolio that can really accelerates and advance our transition into a rare disease company.

我是約書亞謝弗。我來回答第二個問題。我們非常積極地尋求將新產品添加到產品組合中，無論是通過內部開發還是利用我們的前藥平台將新產品引入管道。但我們也在非常積極地尋找潛在的併購許可交易，任何數量的結構都可以將額外的產品引入我們的產品組合，從而真正加速和推進我們向罕見病公司的轉型。

Having said that, we're looking for opportunities that are synergistic with arimoclomol and where we can leverage a commercial organization and a development organization that is really focused in on the rare disease capabilities that we're building.

話雖如此，我們正在尋找與 arimoclomol 協同的機會，並且我們可以利用商業組織和真正專注於我們正在建立的罕見疾病能力的開發組織。

Louise, this is Rich. Just to add to all of that. I think clearly, the priorities today are the resubmission and approval and potential launch for arimoclomol followed closely by completing the Phase II program in idiopathic hypersomnia for 7 -- 1077 and advancing that into a Phase III trial.

路易絲，這是里奇。只是為了添加所有這些。我清楚地認為，今天的優先事項是 arimoclomol 的重新提交和批准以及潛在的啟動，緊隨其後的是完成 7-1077 名特發性嗜睡症的 II 期計劃，並將其推進到 III 期試驗。

To your question, we want to generate the necessary data in this Phase II program for 1077 to tee up Phase III pivotal program that can differentiate the product in the marketplace, and that's the goal there. Beyond that, we're always looking for good opportunities. At the same time, we understand the priorities are advancing the existing pipeline.

對於你的問題，我們希望在 1077 的第二階段計劃中生成必要的數據，以啟動可以在市場上區分產品的第三階段關鍵計劃，這就是那裡的目標。除此之外，我們一直在尋找好的機會。同時，我們了解到優先事項是推進現有管道。

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。

I have a few. Actually, you mentioned actually in your press release and in the script, specifically extending exclusivity of your pipeline assets with a life cycle management, and that kind of jumped out at me. I was wondering, can you just remind us what is the current, I guess, IP landscape of your development assets? And what are we thinking about in terms of life cycle management. Is this just new IP you're working on? Or are there actual product innovations that are already in the hopper longer term? And then I have a follow-up.

我有幾個。實際上，您實際上在新聞稿和腳本中提到過，特別是通過生命週期管理來擴展您的管道資產的排他性，這讓我大吃一驚。我想知道，您能否提醒我們您的開發資產的當前 IP 格局是什麼？我們在生命週期管理方面考慮了什麼。這只是您正在開發的新 IP 嗎？或者是否有長期存在於料斗中的實際產品創新？然後我有一個後續行動。

Yes. Oren, I'll ask Travis to address specifically. But 1 of the things I'll preface it by saying 1 of the things that really excited me about these opportunities in rare diseases and looking at products like arimoclomol as we have this terrific internal capability to not only discover new assets, but to extend life cycle of those assets. And so we are very intent on doing both. And so unlike a lot of companies, I mentioned in my prepared remarks, we're a development stage company with revenue.

是的。奧倫，我會請特拉維斯具體說明。但我會先說一件事，讓我對罕見疾病的這些機會感到非常興奮，並研究像 arimoclomol 這樣的產品，因為我們擁有這種強大的內部能力，不僅可以發現新資產，還可以延長生命這些資產的循環。因此，我們非常有意做到這兩點。因此，與許多公司不同，我在準備好的發言中提到，我們是一家有收入的發展階段公司。

We're also a development stage company focusing on rare diseases with this internal capability that I'm not sure other companies can mimic. So bringing all of that to bear in terms of creating value for the future is really important to us. And so I think that's the underpinnings, if you will, behind those statements. With that, Travis, do you want to address maybe a little more specifically the mechanics of what we're doing?

我們也是一家專注於罕見疾病的發展階段公司，我不確定其他公司能否模仿這種內部能力。因此，將所有這些用於為未來創造價值對我們來說非常重要。所以我認為這就是這些陳述背後的基礎，如果你願意的話。那麼，特拉維斯，你想更具體地談談我們正在做的事情的機制嗎？

Yes. As far as the IP question, Oren, arimoclomol has patents issued and pending that would run well into the 20/40s. Now those patents are not based on composition of matter like we would like to focus on. So of course, that's where Rich is alluding to our ability to expand upon IP. You're always aware too, with a rare drug in a pediatric area, it's going to be 7.5 years of orphan exclusivity. For KP1077, those patents run until 2037 and beyond. Those are, of course, composition of matter-based patents.

是的。至於知識產權問題，Oren，arimoclomol 已經發布和正在申請的專利將持續到 20/40 年代。現在這些專利並不像我們想要關注的那樣基於物質的組成。當然，這就是 Rich 暗示我們擴展 IP 的能力的地方。你也總是知道，在兒科領域使用一種罕見的藥物，這將是 7.5 年的孤兒獨占期。對於 KP1077，這些專利將持續到 2037 年及以後。當然，這些是基於物質的專利的組合。

Okay. Appreciate it. So we're thinking primarily about extending arimoclomol exclusivity well beyond the orphan period. is how I'm interpreting that, correct?

好的。欣賞它。因此，我們主要考慮將 arimoclomol 的獨家經營權延長到孤儿期之後。我是這樣解釋的，對嗎？

That's right.

這是正確的。

Right Okay. And on arimoclomol, I guess, to build upon the first question today -- regarding that confirmatory evidence and the 4-year safety data and everything you need to do for the FDA filing should I think of this 4-year data as sort of clearing the lane and in and of itself potentially addressing any FDA skepticism to the extent it might have existed at some point going forward? Or is there significantly more "confirmatory evidence" that you still need to do separate from that? And where does that stand? Can you give us any clarity on sort of progress on that front?

好吧。關於 arimoclomol，我猜想，以今天的第一個問題為基礎——關於確認證據和 4 年安全數據，以及你需要為 FDA 備案做的一切，我是否應該將這 4 年數據視為一種清理車道及其本身可能會解決任何 FDA 的懷疑，以至於它可能在未來的某個時候存在？還是有更多的“確鑿證據”你還需要分開做？那是什麼意思呢？您能否讓我們清楚地了解這方面的進展情況？

Travis, do you want to fill that?

特拉維斯，你想填補嗎？

Sure. No more clarity, unfortunately, Oren, than what we kind of stated before, what I said before. The data, I believe, from the 4-year extension arm is very helpful, especially if you look in light of the [Amylyx] approval earlier this year where they use the extension arm to show increased survivability. Here, we're looking at kind of the robustness of the effect and how it sustain kind of this lower trend of progression in the disease for a long period of time. Now of course, without a placebo in that portion.

當然。不幸的是，Oren，沒有比我們之前所說的更清楚的了，我之前說過的。我相信，來自 4 年延長臂的數據非常有幫助，特別是如果你看看今年早些時候 [Amylyx] 的批准，他們使用延長臂來顯示更高的生存能力。在這裡，我們正在研究這種效果的穩健性，以及它如何在很長一段時間內維持這種疾病進展的較低趨勢。現在當然，那部分沒有安慰劑。

But for the most part, that's the additional step of what's not been disclosed, the additional information that we have available to us to provide. I think that and everything that Orphazyme generated in the past as well as putting that all together an accretive story will be compelling, more compelling certainly than at the time of the CRL and certainly something that we'll at least in part, if not in its entirety discussed with the agency before the resubmission.

但在大多數情況下，這是未披露的額外步驟，我們可以提供的額外信息。我認為，Orphazyme 過去產生的一切，以及將所有這些放在一起，一個增值的故事將是引人注目的，肯定比 CRL 時更引人注目，當然我們至少會部分地，如果不是在在重新提交之前與該機構進行了整體討論。

Okay. And lastly on KP1077. I think you mentioned brain fog on multiple occasions as a key end points you're looking at, can you just remind us based on your interactions with the FDA or understanding of the landscape in general, what do you see as the necessary hurdle in terms of endpoints for approvability? And to what extent do you believe you need to show additional end points like brain fog or others to differentiate from off-label wakefulness or agents or stimulants?

好的。最後是 KP1077。我認為你多次提到腦霧是你正在尋找的關鍵終點，你能否根據你與 FDA 的互動或對總體景觀的理解來提醒我們，你認為在術語方面的必要障礙是什麼端點的批准？您認為在多大程度上需要顯示額外的終點，如腦霧或其他終點，以區別於標籤外的清醒或藥物或興奮劑？

Oren, it's Rich. I'll just maybe preface to comment here by stating that clearly, the brain fog and other exploratory endpoints are being looked at in this Phase II trial. We're obviously focusing on approvability, which will be driven by the primary but then enhancing the label and the commercial opportunity for the product in a competitive set or a competitive world with some of these other endpoints. I think it's perhaps too early to comment, specifically on the magnitude of effect.

奧倫，它是豐富的。我可能只是在這裡發表評論的序言，清楚地說明，在這個 II 期試驗中正在研究腦霧和其他探索性終點。我們顯然專注於認可度，這將由主要驅動，但隨後會在競爭環境或具有其他一些端點的競爭世界中增強產品的標籤和商業機會。我認為現在評論可能還為時過早，特別是影響的程度。

But clearly, we'll assess that in this Phase II program and build whatever is appropriate into the Phase III protocol, which will then serve as a basis for approvability in a label. But fair to say that it's a little too early to call. But I want to reemphasize that as we think about the company moving forward and we think about commercializing these assets ourselves, we want to ensure that we're creating products that can be highly competitive, command premium pricing in the market. And moreover, allow us to go out and create the sort of value that we foresee for the company through that process.

但很明顯，我們將在這個第二階段計劃中對其進行評估，並將任何合適的內容構建到第三階段協議中，然後將其作為標籤批准的基礎。但公平地說，現在下結論還為時過早。但我想再次強調，當我們考慮公司向前發展並考慮自己將這些資產商業化時，我們希望確保我們正在創造具有高度競爭力的產品，並在市場上獲得溢價。此外，讓我們走出去，通過這個過程為公司創造我們預見的那種價值。

Our next question comes from Sumant Kulkarni with Canaccord Genuity.

我們的下一個問題來自 Canaccord Genuity 的 Sumant Kulkarni。

This is Kyle for Sumant again. A quick follow-up. On EAP gross revenue, we see that the new guidance is roughly [$2 million] annualized versus a prior estimate of $12 million. We are curious what are the factors affecting this number? And do you think this new guidance is driven more so by a function of price or a function of patient size?

這又是蘇曼特的凱爾。快速跟進。在 EAP 總收入方面，我們看到新指南的年化率約為 [200 萬美元]，而之前的估計為 1200 萬美元。我們很好奇影響這個數字的因素有哪些？你認為這個新指南更多地是由價格函數或患者規模函數驅動的嗎？

Well, thanks for the question. And really, it's actually not new guidance. I think sometimes when we spoke, we talked about gross revenue being about EUR 1 million per month, and that really is unchanged. What we tried to do in today's guidance though is to account for the around 30% or 35% clawback liability, which we always have to recognize when we put out our financial statements. So that's really the difference there is simply giving you guidance of net revenue, which is around $2 million a quarter versus the gross revenue that we've sometimes spoken about before.

好吧，謝謝你的提問。實際上，這並不是新的指南。我想有時候我們說話的時候，我們談到的總收入約為每月 100 萬歐元，但實際上並沒有改變。不過，我們在今天的指南中試圖做的是解釋大約 30% 或 35% 的回撥責任，我們在發布財務報表時始終必須承認這一點。所以這就是真正的區別，只是給你淨收入的指導，淨收入大約是每季度 200 萬美元，而我們之前有時會談到總收入。

Thank you. This concludes the Q&A portion of today's call. I would now like to turn the call over back to Richard Pascoe for any additional or closing remarks.

謝謝。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 Richard Pascoe，以徵求任何補充意見或結束意見。

Thank you, operator. And first of all, I want to thank all of our employees and leaders, in particular, my colleagues here today around the table for their tireless efforts to bring Zevra Therapeutics into a very strong position for 2023 and beyond. It's an exciting time for us, and I appreciate their support and hard efforts to get us to where we want to be. I also want to thank all of our shareholders for your continued support and for all of those that have joined us today on the call, we appreciate your interest and your questions, and we look forward to speaking with you in the future. Thank you.

謝謝你，運營商。首先，我要感謝我們所有的員工和領導者，特別是今天坐在桌旁的我的同事們，感謝他們不懈努力，使 Zevra Therapeutics 在 2023 年及以後處於非常有利的地位。這對我們來說是一個激動人心的時刻，我感謝他們的支持和辛勤努力，讓我們達到了我們想要的目標。我還要感謝我們所有的股東一直以來的支持，感謝今天加入我們電話會議的所有人，我們感謝您的興趣和問題，我們期待著在未來與您交談。謝謝。

This concludes today's Zevra Therapeutics Fourth Quarter and Full Year 2022 Earnings Call and webcast. You may disconnect your line at this time, and have a wonderful day.

今天的 Zevra Therapeutics 第四季度和 2022 年全年收益電話會議和網絡廣播到此結束。您可以在此時斷開您的線路，並度過美好的一天。