Talphera Inc (TLPH) 2022 Q4 法說會逐字稿

Welcome to the AcelRx 2022 Full Year and Fourth Quarter Financial Results Conference Call. This call is being webcast live via the Events page on the Investors section of AcelRx's website at www.acelrx.com. This call is the property of AcelRx, and any recording, reproduction or transmission of this call without the expressed written consent of AcelRx is strictly prohibited.

歡迎參加 AcelRx 2022 年全年和第四季度財務業績電話會議。此電話會議通過 AcelRx 網站 www.acelrx.com 投資者部分的活動頁面進行網絡直播。此通話是 AcelRx 的財產，未經 AcelRx 明確書面同意，嚴禁錄製、複製或傳輸此通話。

As a reminder, today's webcast presentation is being recorded. You may listen to a replay of this webcast by going to the Investors section of AcelRx's website. (Operator Instructions)

提醒一下，今天的網絡廣播演示正在錄製中。您可以訪問 AcelRx 網站的投資者部分收聽該網絡廣播的重播。 （操作員說明）

I would now like to turn the call over to Raffi Asadorian, AcelRx Chief Financial Officer.

我現在想把電話轉給 AcelRx 首席財務官 Raffi Asadorian 。

Thank you, Andrew. Thank you for joining us on the call today. This afternoon, we announced our full year and fourth quarter 2022 financial results and associated business updates in a press release. This press release can be found with the investors within the Investors section of our website. With me today are Vince Angotti, our Chief Executive Officer; and Dr. Pam Palmer, AcelRx's Founder and Chief Medical Officer.

謝謝你，安德魯。感謝您今天加入我們的電話會議。今天下午，我們在新聞稿中公佈了 2022 年全年和第四季度的財務業績以及相關業務更新。本新聞稿可在我們網站的投資者部分與投資者一起找到。今天和我在一起的是我們的首席執行官 Vince Angotti； AcelRx 的創始人兼首席醫療官 Pam Palmer 博士。

Before we begin, I want to remind listeners that during this call, we will likely make forward-looking statements within the meaning of the federal securities laws. These forward-looking statements involve risks and uncertainties regarding the operations and future results of AcelRx. Please refer to our press release in addition to the company's periodic, current and annual reports filed with the Securities and Exchange Commission for a discussion of the risks associated with such forward-looking statements.

在我們開始之前，我想提醒聽眾，在這次電話會議中，我們可能會做出聯邦證券法意義上的前瞻性陳述。這些前瞻性陳述涉及與 AcelRx 的運營和未來結果有關的風險和不確定性。請參閱我們的新聞稿以及公司向證券交易委員會提交的定期、當前和年度報告，以討論與此類前瞻性陳述相關的風險。

I'll now hand the call over to Vince.

我現在將電話轉給文斯。

Thank you, Raffi, and good afternoon, everyone. This past year has been a transformative one for AcelRx. We're pleased to update you today after executing on our previously stated goal of divesting DSUVIA, our first commercial product to Alora Pharmaceuticals. Alora is a well-resourced operation with extensive experience commercializing products in hospitals, expertise in the manufacturing and sales of controlled substances and a team of over 200 salespersons.

謝謝你，Raffi，大家下午好。過去的一年對 AcelRx 來說是變革性的一年。在執行我們之前宣布的將我們的第一個商業產品 DSUVIA 剝離給 Alora Pharmaceuticals 的目標之後，我們很高興今天向您更新。 Alora 是一家資源充足的公司，擁有豐富的醫院產品商業化經驗、受控物質製造和銷售方面的專業知識以及一支由 200 多名銷售人員組成的團隊。

In addition to the 15% royalty on net commercial sales and the $116.5 million in sales-based milestones in our agreement with Alora, we're able to leverage our invested time and resources working with the Department of Defense, the single largest customer for DSUVIA through a 75% royalty on DoD net sales. In today's press release, we announced a new replay of this webcast by going to the via, including a presentation at the Anesthesiology Annual Meeting 2022 by the Uniform Services University of the Health Sciences on DSUVIA for Battlefield Pain Management. In the presentation, the authors once again recommended the adoption of DSUVIA by the Department of Defense to improve pain management in the battlefield setting.

除了我們與 Alora 達成的協議中淨商業銷售額的 15% 特許權使用費和基於銷售額的 1.165 億美元里程碑之外，我們還能夠利用我們投入的時間和資源與 DSUVIA 的最大單一客戶國防部合作通過 DoD 淨銷售額的 75% 的特許權使用費。在今天的新聞稿中，我們通過 via 宣布了該網絡廣播的新重播，包括健康科學統一服務大學在 2022 年麻醉學年會上關於 DSUVIA 戰場疼痛管理的演講。在演示中，作者再次建議國防部採用 DSUVIA 來改善戰場環境中的疼痛管理。

These and other recent publications provide continued endorsement of the value of DSUVIA for acute pain management. Now the DoD has many different purchasing points across various areas of the armed services. We remain focused on the U.S. Army since the largest opportunity for DSUVIA is within their sets, kits and outfits or SKOs for deploying troops. The DoD is a very important relationship, and we believe that this will provide long-term value for our shareholders.

這些和其他最近的出版物繼續認可 DSUVIA 在急性疼痛管理中的價值。現在，國防部在武裝部隊的各個領域都有許多不同的採購點。我們仍然關注美國陸軍，因為 DSUVIA 的最大機會在於他們的佈景、裝備和裝備或用於部署部隊的 SKO。國防部是一個非常重要的關係，我們相信這將為我們的股東提供長期價值。

After the expected closing of the DSUVIA transaction in the coming days, we'll have transformed the company and are confident that we can leverage our successful development expertise and obtaining approval for our late-stage high-value assets.

在未來幾天預期完成 DSUVIA 交易後，我們已經對公司進行了轉型，並且有信心我們可以利用我們成功的開發專業知識並獲得對我們後期高價值資產的批准。

In particular, we're focusing on our lead nafamostat program, Niyad, which has FDA breakthrough designation and is being developed for use in the U.S. as an anticoagulant for extra carpool circuits in particular, such as dialysis. As such, we wanted to provide visibility into Niyad's potential, which we believe is a key component of the company's value.

特別是，我們專注於我們的領先 nafamostat 項目 Niyad，它具有 FDA 的突破性指定，並且正在開髮用於在美國用作額外拼車迴路的抗凝劑，特別是透析等。因此，我們希望展示 Niyad 的潛力，我們認為這是公司價值的關鍵組成部分。

Nafamostat is approved and widely used as an anticoagulant for dialysis in Japan and South Korea. We, AcelRx, are the first developer for such use in the United States. And if approved of Niyad would be the only regional anticoagunant labeled for use in this indication in the U.S. Clotting in the dialysis filter during continuous renal replacement therapy or CRRT is a major limitation to the patient receiving effective dialysis. In addition, filter clotting results in loss of red blood cells, platelets and clotting factors often requiring transfusions for the patient.

Nafamostat 在日本和韓國被批准並廣泛用作透析抗凝劑。我們 AcelRx 是美國第一家此類用途的開發商。如果 Niyad 獲得批准，將成為美國唯一標示用於該適應症的區域性抗凝劑。在連續腎臟替代治療或 CRRT 期間，透析過濾器中的凝血是患者接受有效透析的主要限制。此外，過濾器凝血導致紅細胞、血小板和凝血因子的損失，通常需要為患者輸血。

For these reasons, the international CRRT guidelines recommend the use of an anticoagulant infused into the dialysis circuit. So today, 2 anticoagulant options exist for CRRT, first Heparin and then their citrate, which is only available under an EUA. Our recent U.S. quantitative market research confirms the urgent medical need for an alternative anticoagulant for use in CRRT.

由於這些原因，國際 CRRT 指南建議使用注入透析迴路的抗凝劑。所以今天，CRRT 有 2 種抗凝劑選擇，首先是肝素，然後是檸檬酸鹽，後者僅在 EUA 下可用。我們最近的美國定量市場研究證實，迫切需要一種替代抗凝劑用於 CRRT。

The study results show that the inherent risks of the currently used products, Heparin, which has used 43% of the time in patients and citrate, which is used in 28% of patients lead physicians cannot use anticoagulants, which again, is below the international standard of care, and the remaining 29% of patients are undergoing CRRT.

研究結果表明，目前使用的產品的固有風險，肝素（43% 的患者使用時間）和檸檬酸鹽（28% 的患者使用時間）導致醫生不能使用抗凝劑，再次低於國際水平護理標準，其餘 29% 的患者正在接受 CRRT。

Consistent with the published literature and our recent quantitative market research, 84% of physicians reported that frequent filter changes occurred when not using an anticoagulant. This not only leads to increased blood loss and an increase in the number of transfusions, but also results in delayed or prolonged treatment time and imposes a burden on health care resources.

與已發表的文獻和我們最近的定量市場研究一致，84% 的醫生報告說，在不使用抗凝劑時會頻繁更換過濾器。這不僅會導致失血量增加和輸血次數增加，還會導致治療時間延誤或延長，給醫療資源造成負擔。

And addition to our market research, detailing the specific adverse events physicians were concerned about regarding Citrate, it included hypocalcemia, citrate safety, alkalosis and others. So in conclusion, we believe that the market opportunity for Niyad is 29% of the patients that are receiving no anticoagulant as well as the 28% of patients that are receiving citrate. This totals almost 60% of the CRRT patients.

除了我們的市場研究外，還詳細說明了醫生擔心的有關檸檬酸鹽的具體不良事件，包括低鈣血症、檸檬酸鹽安全性、鹼中毒等。因此，總而言之，我們認為 Niyad 的市場機會是 29% 的未接受抗凝劑的患者以及 28% 的接受檸檬酸鹽的患者。這幾乎佔 CRRT 患者的 60%。

This market research is significant. We plan to submit it for peer-reviewed publication in the second quarter. We've already completed the production of the initial development batch in Niyad and are now completing stability product testing in preparation for planned EUA submission. We remain on target to submit this EUA in the second quarter. And in addition, having already received an ICD-10 CMS procedural code for reimbursement, we're proceeding with early commercial planning. Niyad is estimated to have a peak sales potential of $200 million, and this is attributed to just the inpatient and outpatient dialysis markets, excluding use in any other extracorporeal circuits. We anticipate that we'll need only a very modest sales force for launching Niyad. Our market research has reinforced that it is clearly an important unmet patient need and we look forward to initiating a single registrational trial in the second half of 2023, of which the primary end points have already been agreed upon by FDA for 160 patient study.

這個市場調查意義重大。我們計劃在第二季度將其提交給同行評審的出版物。我們已經在 Niyad 完成了初始開發批次的生產，現在正在完成穩定性產品測試，為計劃中的 EUA 提交做準備。我們仍按目標在第二季度提交此 EUA。此外，在收到 ICD-10 CMS 報銷程序代碼後，我們正在著手進行早期商業規劃。據估計，Niyad 的最高銷售潛力為 2 億美元，這僅歸因於住院和門診透析市場，不包括在任何其他體外迴路中的使用。我們預計我們將只需要非常適度的銷售人員來推出 Niyad。我們的市場研究證實，這顯然是一個重要的未滿足的患者需求，我們期待在 2023 年下半年啟動一項註冊試驗，FDA 已經就 160 名患者研究的主要終點達成一致。

Consistent with our priority to advance our pipeline of late-stage assets, we continue to make progress towards filing NDAs for our ephedrine and phenylephrine prefilled syringes. As such, our other near-term corporate milestone expected by the end of Q2 2023 is the filing of a new drug application for our prefilled syringe of ephedrine branded as Fedsyra, again, branded as Fedsyra. The benefits of prefilled syringes include less waste, improved safety and the convenience of not having to dilute and prepare the surrendering advance of procedures, resulting in a shift towards their use.

與我們推進後期資產管道的優先事項一致，我們繼續在為我們的麻黃鹼和去氧腎上腺素預裝注射器提交 NDA 方面取得進展。因此，我們預計到 2023 年第二季度末的另一個近期公司里程碑是為我們的麻黃鹼預裝注射器提交新藥申請，該注射器品牌為 Fedsyra，再次品牌為 Fedsyra。預充式註射器的好處包括減少浪費、提高安全性以及無需稀釋和準備放棄程序的便利性，從而轉向使用。

Based on our partner Aguettant experience in Europe, the expected shelf life of Fedsyra is 3 years. Nearly all of the currently used to ephedrine prefilled syringes are made by compounding pharmacies, which have an inherent short shelf life and well-known risks for contamination. The ability of physicians to have available a convenient pre-filled terminally sterilized efferent syringe that has a 3-year self-life will be a significant improvement and advantage for the overall health care system.

根據我們在歐洲的合作夥伴 Aguettant 的經驗，Fedsyra 的預期保質期為 3 年。幾乎所有目前使用的麻黃鹼預充式註射器都是由複合藥房生產的，它們具有固有的保質期短和眾所周知的污染風險。醫生能夠使用方便的預填充末端滅菌輸出注射器，其使用壽命為 3 年，這將是整個醫療保健系統的重大改進和優勢。

As stated previously, we believe that the market opportunities for the assets exceeds $100 million, and we believe that we'll be able to obtain a significant share of this market with minimal investment since much of the commercialization efforts are expected to be through contracting with group purchasing organizations and hospital networks.

如前所述，我們相信資產的市場機會超過 1 億美元，我們相信我們將能夠以最少的投資獲得該市場的重要份額，因為大部分商業化工作預計將通過與團購組織和醫院網絡。

And just to put the market potential for a pre-filled syringe into better context, A ready-to-use bowl of ephedrine, not a prefilled syringe, but a ready-to-use [phenylephrine] launched in 2020 and reported that $30 million in sales in only its second year of launch. With potential approval of the NDA for Fedsyra, commercialization could occur as soon as the first half of next year.

為了更好地了解預裝注射器的市場潛力，一碗即用型麻黃鹼，不是預裝注射器，而是 2020 年推出的即用型 [去氧腎上腺素]，據報導價值 3000 萬美元僅在推出第二年的銷售額。隨著 Fedsyra 的 NDA 可能獲得批准，商業化最早可能在明年上半年發生。

As we stated in today's press release, both the Niyad and Fedsyra regulatory submissions will bring us closer to delivering important advancements for the health care system and increasing value for our shareholders.

正如我們在今天的新聞稿中所述，Niyad 和 Fedsyra 提交的監管文件將使我們更接近於為醫療保健系統提供重要進步並為我們的股東增加價值。

In conclusion, I'm pleased to report that we believe we're well positioned to execute on a new successful chapter for AcelRx. We've divested our opioid product to focus on our proprietary anticoagulant program which we believe has the potential to reach $200 million in peak sales. We've made significant progress in our clinical development program of Niyad, and we're preparing to move to a registrational trial with endpoints agreed upon by FDA and later this year.

總之，我很高興地報告，我們相信我們已經做好準備，為 AcelRx 開啟一個新的成功篇章。我們已經剝離了我們的阿片類藥物產品，專注於我們專有的抗凝血劑項目，我們相信該項目的銷售高峰期有可能達到 2 億美元。我們在 Niyad 的臨床開發計劃中取得了重大進展，我們正準備進行一項註冊試驗，其終點將在今年晚些時候獲得 FDA 的同意。

We're also on track to file our NDA for our first prefilled syringe product candidate, Fedsyra, which also has significant upside potential for the company if approved. Importantly, we'll continue with our efficient approach to managing cash as we accomplish these key milestones. I'll now hand the call over to Raffi to take you through the fourth quarter financial results.

我們也有望為我們的第一個預充式註射器候選產品 Fedsyra 提交 NDA，如果獲得批准，它對公司也有巨大的上行潛力。重要的是，在我們完成這些關鍵里程碑時，我們將繼續採用有效的方法來管理現金。我現在將電話轉給拉菲，讓您了解第四季度的財務業績。

Thank you, Vince. The planned closing of the DSUVIA transaction with Alora Pharmaceuticals in the coming days, is expected to add value through reduced cash burn and leveraging via Alora commercial infrastructure to collect royalties and milestones on DSUVIA sales. We're excited to work with Alora on the transition and supporting the potential long-term value creation from the transaction.

謝謝你，文斯。計劃在未來幾天內完成與 Alora Pharmaceuticals 的 DSUVIA 交易，預計將通過減少現金消耗和利用 Alora 商業基礎設施收取 DSUVIA 銷售的特許權使用費和里程碑來增加價值。我們很高興與 Alora 合作進行轉型，並支持交易中潛在的長期價值創造。

Our full year 2022 DSUVIA sales totaled $1.8 million which was a 76% increase over 2021 despite a significant reduction in our commercial investment to conserve cash. We believe Alora's ownership of DSUVIA will deliver a significant increase in DSUVIA sales after the initial transition period. As Vince mentioned, our focus now turns to our lead program in nafamostat for which significant potential near-term milestones exist as well as our first prefilled syringe NDA submission, Fedsyra.

我們 2022 年全年的 DSUVIA 銷售額總計 180 萬美元，比 2021 年增長了 76%，儘管我們大幅減少了商業投資以節省現金。我們相信 Alora 對 DSUVIA 的所有權將在最初的過渡期後顯著增加 DSUVIA 的銷售額。正如 Vince 提到的，我們現在的重點轉向了我們在 nafamostat 的領先項目，該項目存在重要的潛在近期里程碑，以及我們提交的第一個預填充注射器 NDA 提交，Fedsyra。

We continue to focus on our cash and ended the year with $20.8 million in cash and investments. Our debt continued to amortize and the balance at the end of the year was $5.4 million. Combined R&D and SG&A expenses for the fourth quarter of 2022 totaled $7.3 million compared to $6.9 million for the fourth quarter of 2021.

我們繼續專注於我們的現金，並在年底以 2080 萬美元的現金和投資結束。我們的債務繼續攤銷，年底餘額為 540 萬美元。 2022 年第四季度的研發和 SG&A 總支出為 730 萬美元，而 2021 年第四季度為 690 萬美元。

Excluding noncash depreciation and stock-based compensation expense, these amounts were $6.6 million for the fourth quarter of 2022 compared to $5.6 million for the fourth quarter of 2021. The increase in combined R&D and SG&A expense in the fourth quarter of 2022 was primarily due to costs associated with the December financing and other legal costs, partially offset by net decreases in R&D and SG&A expenses compared to the fourth quarter of 2021.

不包括非現金折舊和基於股票的補償費用，這些金額在 2022 年第四季度為 660 萬美元，而 2021 年第四季度為 560 萬美元。2022 年第四季度研發和 SG&A 合併費用的增加主要是由於與 12 月融資和其他法律費用相關的費用，部分被研發和 SG&A 費用與 2021 年第四季度相比的淨減少所抵消。

We expect our cash operating expenses in 2023 to range from $16 million to $20 million, which include costs related to a planned launch of Niyad under an EUA, initiating the single registrational study for Niyad and the PDUFA fee for Fedsyra for which an NDA submission is expected in the second quarter of this year.

我們預計我們 2023 年的現金運營費用將在 1600 萬美元至 2000 萬美元之間，其中包括與根據 EUA 計劃推出 Niyad 相關的費用、啟動 Niyad 的單一註冊研究以及 Fedsyra 的 PDUFA 費用，其 NDA 提交是預計在今年第二季度。

'll now turn the call back over to Vince.

現在將電話轉回文斯。

Thank you, Raffi. I'd now like to open the line for any questions you might have. Andrew?

謝謝你，拉菲。我現在想為您可能有的任何問題打開熱線。安德魯？

(Operator Instructions) The first question comes from Brandon Folkes with Cantor Fitzgerald.

（操作員說明）第一個問題來自 Brandon Folkes 和 Cantor Fitzgerald。

Congratulations on all the progress. Maybe I'll just start on DSUVIA. Can you just talk about who drives the military procurement with this deal? Are there any current DoD orders? And then just to sort of -- will you have a continued involvement on the DoD side or just staying ahead of the DOD? I'll ask my second question, then I'll hop across to Niyad.

祝賀所有的進步。也許我會從 DSUVIA 開始。你能談談誰推動了這筆交易的軍事採購嗎？有任何當前的國防部命令嗎？然後只是有點 - 你會繼續參與國防部方面的工作還是只是保持領先於國防部？我會問我的第二個問題，然後我會跳到 Niyad。

Sure. So the DoD purchasing is decentralized when you consider it from the different branches of the military, that being that the Navy, the Air Force the Coast Guard and the Army all purchased through different avenues. And even within the Army, in particular, you have different avenues that drive it.

當然。因此，當你從軍隊的不同部門考慮時，國防部的採購是分散的，即海軍、空軍、海岸警衛隊和陸軍都是通過不同的渠道採購的。甚至在陸軍內部，你也有不同的途徑來推動它。

So for instance, we have relationships that we work with, with the Defense Health Agency, the Defense Logistics Agency, (inaudible). Working on contingency contracts with the Army outside of those particular channels and of course, the (inaudible) so it's a myriad of different channels within the military. The largest driver, though, will be through these SKOs which are often driven centrally by a single purchaser for troop deployment and readiness.

因此，例如，我們與國防衛生局、國防後勤局（聽不清）有合作關係。在這些特定渠道之外與陸軍簽訂應急合同，當然還有（聽不清），所以它是軍隊內部的無數不同渠道。不過，最大的驅動力將來自這些 SKO，這些 SKO 通常由單一購買者集中驅動，用於部隊部署和戰備。

These relationships have been fostered over time. It takes time. But we feel like we're really advancing them here just in the course of the past year to a new level. And part of it, honestly, is the tension that builds around the world and the challenges with the conflict and the creation for potential more deployments, unfortunately for our U.S. armed services. So we're going to continue to maintain those relationships, drive them and hopefully be able to supply them at the right quantity and timing as those things escalate.

隨著時間的推移，這些關係得到了培養。這需要時間。但我們覺得，就在過去的一年裡，我們真的把它們推進到了一個新的水平。老實說，部分原因是世界各地的緊張局勢、衝突帶來的挑戰以及可能的更多部署的創造，不幸的是我們的美國武裝部隊。因此，我們將繼續維持這些關係，推動它們，並希望隨著這些事情的升級，能夠在正確的數量和時間提供它們。

Yes. It's our responsibility, Brandon. That remains with us.

是的。這是我們的責任，布蘭登。這仍然與我們同在。

Okay. Great. as good to hear. And then so maybe just shifting gears to Niyad. Maybe just a 2 part that probably go together. Any color on the steps outstanding from here on in, in terms of submitting the EUA, would you -- you sound quite confident. We're almost at 2Q. So is it fair to just think of it as procedural from here on in. And then along those lines, in terms of manufacturing of Niyad, can you just remind us on this EUA will you need an inspection? And then secondly, staying on manufacturing, can you just talk about your ability to supply the market just given that 60% figure you put out today?

好的。偉大的。好聽。然後也許只是換檔到 Niyad。也許只有一個 2 部分可能在一起。從現在開始，在提交 EUA 方面，任何突出步驟的顏色，你會不會 - 你聽起來很自信。我們快到第二季度了。因此，從現在開始將其視為程序是否公平。然後沿著這些思路，就 Niyad 的製造而言，您能否就此 EUA 提醒我們您是否需要檢查？然後其次，繼續製造，你能談談你今天提出的 60% 的數字供應市場的能力嗎？

Sure. I can address the first part of that question, and I'll continue to turn it over to Raffi and Pam as it relates to some of the supply. So we've been working on the EUA for a year at least in preparation. And part of -- just to give you an example of the quantitative market research we just completed that started, I think, in the fourth quarter last year with results in the first quarter this year to continue to show the FDA the elevated use of CRRT in the hospitals from a post-COVID standpoint, pre and post, if you really want to consider it post right now.

當然。我可以解決這個問題的第一部分，我會繼續把它交給 Raffi 和 Pam，因為它與一些供應有關。因此，我們至少在準備期間就 EUA 工作了一年。並且部分 - 只是給你一個我們剛剛完成的定量市場研究的例子，我認為，從去年第四季度開始，今年第一季度的結果繼續向 FDA 展示 CRRT 的使用增加從後 COVID 的角度來看，在醫院裡，如果你真的想現在就考慮它的話。

So we have put all of our work together related to the package and the 1 remaining aspect, most importantly, has remained CMC. So we've got the balance of the package basically ready to go. If you recall, in the early discussions around the EUA with the FDA, and I apologize for all these 3-letter acronyms. The FDA's concentration was on the proper manufacturing of the product. So over the course of the past year, that has been our focus.

因此，我們將所有與軟件包相關的工作放在一起，剩下的 1 個方面，最重要的是，仍然是 CMC。所以我們基本上已經準備好了包裹的餘額。如果你還記得，在與 FDA 圍繞 EUA 的早期討論中，我為所有這些 3 個字母的首字母縮略詞道歉。 FDA 的重點是產品的正確製造。因此，在過去的一年中，這一直是我們的重點。

And as we mentioned, we've got product up on stability. It's important that we've got accelerated stability. Some people might not know what that means. What that really means is stability testing beyond the normal ranges of temperature and humidity. So the concept is if degradation is going to be happening over time, you can simulate degradation in extreme environments, and that will show you a longer period of time based off of that simulation of stability of the product.

正如我們提到的，我們已經在穩定性上提高了產品。重要的是我們獲得了加速的穩定性。有些人可能不知道這意味著什麼。這真正意味著超出正常溫度和濕度範圍的穩定性測試。所以這個概念是，如果退化會隨著時間的推移發生，你可以模擬極端環境中的退化，這將根據產品穩定性的模擬向你展示更長的時間。

For us, humidity is a nonevent. It's obviously a sealed vial. We've got 3 months of good solid data at room and accelerated temperatures, that being 25 degrees centigrade 40 degrees integrate in the accelerated portion. And our GMP initial release test data looks very good with only 1 test still remaining, and that's in sterility.

對我們來說，濕度是小事。這顯然是一個密封的小瓶。我們在室溫和加速溫度下獲得了 3 個月的良好固體數據，即 25 攝氏度 40 度集成在加速部分。我們的 GMP 初始發布測試數據看起來非常好，只剩下 1 個測試，而且是無菌狀態。

So we feel very good about the progress we've made on CMC. We have partnerships related to supply relative to ex-U.S. suppliers for both the API and finished products. So we're well on our way as it relates to this.

因此，我們對在 CMC 上取得的進展感到非常滿意。我們有與美國以外的供應相關的合作夥伴關係。 API 和成品的供應商。所以我們在這方面進展順利。

I think you had 1 more question. The question about inspection. The need for inspection for EUA. There's no need for an inspection for an EUA. Obviously, for a full approval, which would come after our clinical study, which we expect to start in the second half of next year. Did that answer all your questions, Brandon?

我想你還有 1 個問題。關於檢查的問題。 EUA檢查的必要性。無需檢查 EUA。顯然，要獲得完全批准，這將在我們的臨床研究之後進行，我們預計該研究將於明年下半年開始。布蘭登，這回答了你所有的問題嗎？

The next question comes from Ed Arce with H.C. Wainwright.

下一個問題來自 Ed Arce 和 H.C.溫賴特。

This is Thomas asking a couple of questions for Ed. So while we are a topic for Niyad, can you discuss what are your expectations under the EUA this year is approved what were commercial traction we expect and perhaps initial thoughts about pricing and annual borrowing used per patient some details on commercial launch?

這是 Thomas 向 Ed 問了幾個問題。因此，雖然我們是 Niyad 的話題，但您能否討論一下您對今年 EUA 的期望是什麼？

Yes. So for Niyad, again, under the EUA, we're confident in our ability to submit I'm sure there'll be dialogue with the FDA as it goes through the process hopefully, for that approval this year. Beyond that, we have to prep either way for a potential commercialization with the EUA. And as we mentioned in the most recent study, we believe our target market is clear.

是的。因此，對於 Niyad，再次，根據 EUA，我們對我們提交的能力充滿信心，我相信在今年獲得批准的過程中，我們會與 FDA 進行對話。除此之外，我們必須為 EUA 的潛在商業化做任何準備。正如我們在最近的研究中提到的，我們相信我們的目標市場是明確的。

That's the market where people are receiving no anticoagulant in CRRT, which is considered below standard of care, which obviously will be a real shame for the United States and our ability to provide health care.

這是人們在 CRRT 中不接受抗凝劑的市場，這被認為低於護理標準，這顯然對美國和我們提供醫療保健的能力來說是一個真正的恥辱。

And the second is the citrate market, in particular, because of the complications and side effects associated with it. When you combine those 2 markets as an opportunity for Niyad's penetration, it's 60% of the CRRT market. We're working on our commercial planning now. As a matter of fact, Dr. Palmer and I are spending time at the CRRT meeting in San Diego tonight and tomorrow.

第二個是檸檬酸鹽市場，尤其是因為與之相關的並發症和副作用。當您將這兩個市場結合起來作為 Niyad 滲透的機會時，它佔 CRRT 市場的 60%。我們現在正在製定商業計劃。事實上，Palmer 博士和我今晚和明天將花時間參加在聖地亞哥舉行的 CRRT 會議。

We've got an advisory board with some of the key experts for CRRT in the United States as well as internationally known next week, a week from this Saturday. We're beginning to start on pricing evaluations, but it's something I won't comment on this call just from a competitive standpoint. But again, we feel very good about the preparation we have for this moving forward in the size of the target market.

下週，也就是從本週六開始的一周，我們已經成立了一個顧問委員會，其中包括美國和國際知名的 CRRT 的一些主要專家。我們開始進行定價評估，但我不會僅從競爭的角度對此次電話會議發表評論。但同樣，我們對在目標市場規模上向前邁進所做的準備感到非常滿意。

I think the other important aspect of this is even though the market is large. When we talk about a $200 million peak sales opportunity and 60% of the existing practice that's occurring in the United States based off the citrate (inaudible) anticoagulant segments. This is not one that we anticipate to require a large commercial infrastructure. We expect it to be very modest. It's a top-down approach based off the key opinion leaders in the nation that drive CRRT guidelines.

我認為另一個重要方面是即使市場很大。當我們談論 2 億美元的銷售高峰機會以及美國 60% 的現有實踐基於檸檬酸鹽（聽不清）抗凝劑部分時。我們預計這不需要大型商業基礎設施。我們希望它非常適度。這是一種自上而下的方法，基於全國推動 CRRT 指南的主要意見領袖。

I think the other important aspect of this is nafamostat is not a new concept to them. Niyad/nafamostat has been used, as we've mentioned, for 30 years in separate countries, including Japan and South Korea. The thought leads in the United States cross mingle and share expertise with those outside of the U.S. So nafamostat is a known entity to them. And they're often asking us when we think we'll be able to have this available for the U.S. so they can provide this anticoagulant to their at-risk patients.

我認為另一個重要方面是 nafamostat 對他們來說並不是一個新概念。正如我們所提到的，Niyad/nafamostat 已經在不同的國家使用了 30 年，包括日本和韓國。美國的思想領袖與美國以外的思想領袖交叉融合併分享專業知識。因此，nafamostat 對他們來說是一個眾所周知的實體。他們經常問我們什麼時候我們認為我們能夠為美國提供這種藥物，這樣他們就可以為他們的高危患者提供這種抗凝劑。

I hope that helps give a bit of a color to it, Thomas. Pam, do you have anything to add relative to the market research that we've conducted most recently relative to CRRT?

Thomas，我希望這有助於給它一些色彩。 Pam，關於我們最近進行的與 CRRT 相關的市場調查，您有什麼要補充的嗎？

No, we're writing up the data right now. It will be submitted in Q2 and likely published in Q3. And we're really excited about possibly being able to in very near term address this sort of deficit in the medical treatment of patients during CRRT. I mean, it's amazing to me that 29% do not get any anticoagulation during CRRT just because of the issues with Heparin and Citrate.

不，我們現在正在寫數據。它將在第二季度提交並可能在第三季度發布。我們真的很高興能夠在很短的時間內解決 CRRT 期間患者醫療方面的這種缺陷。我的意思是，令我驚訝的是，僅因為肝素和檸檬酸鹽的問題，29% 的患者在 CRRT 期間沒有接受任何抗凝治療。

Thomas, I would just add, we don't know -- should we receive an EUA. We don't know when that would come. There's no specific time frame on the FDA review of that. So we don't know if that's going to come in 1 month or it's going to come in 6 months. So to give any expectations on sales would not be a reasonable way to estimate this at this point. I think we can give more detail when we receive an EUA later this year.

Thomas，我只想補充一點，我們不知道——我們是否應該收到 EUA。我們不知道那會在什麼時候到來。 FDA 對此的審查沒有具體的時間框架。所以我們不知道它會在 1 個月內出現還是會在 6 個月內出現。因此，在這一點上給出任何銷售預期都不是一種合理的估計方式。我認為我們可以在今年晚些時候收到 EUA 時提供更多細節。

Got it. So I guess just to clarify, so the decision after the EUA is filed a decision is expected by the end of this year.

知道了。所以我想只是為了澄清一下，所以 EUA 提交決定後的決定預計將在今年年底前做出。

Well, you'd hope that they have no firm guidelines on review time lines like they do for classic PDUFA. So as we research EUAs that have been reviewed in the past, month or 2 months could be longer. So we just can't give you a defined time line on that.

好吧，你會希望他們沒有像經典 PDUFA 那樣的嚴格的審查時間表指南。因此，當我們研究過去審查過的 EUA 時，一個月或兩個月可能會更長。所以我們不能給你一個明確的時間線。

I think what's important even beyond that, Thomas, and maybe some people are asking about is we are intending even beyond the EUA to move forward with the registrational trial in the second half of this year. And this is a very clear design trial with endpoints already agreed upon by the FDA. So there's not a lot of, what I'll call, debate left on how to execute this trial.

Thomas，我認為更重要的是，Thomas，也許有些人會問，我們打算在 EUA 之外繼續推進今年下半年的註冊試驗。這是一個非常明確的設計試驗，其終點已經得到 FDA 的同意。因此，關於如何執行該試驗的爭論不多，我稱之為爭論。

Pam, maybe you can comment on the preparation we've made the endpoints, et cetera, on the trial, so people are clear on how we feel it's very simple to execute.

帕姆，也許你可以評論我們在試驗中為終點等所做的準備，這樣人們就會清楚我們認為它執行起來非常簡單。

Yes, the end of the 160 patients, which is actually quite a small trial. It's 80 active placebo has already been agreeable to the FDA as is the primary and key secondary endpoints for the trial. And so yes, CRO selection, getting -- moving forward with the finalization of the statistics for the protocol and picking clinical sites is what we're actively doing right now. So and that's a key part of our Advisory Board coming up.

是的，160 名患者結束，這實際上是一個相當小的試驗。它的 80 種活性安慰劑已經獲得 FDA 的認可，該試驗的主要和關鍵次要終點也是如此。所以是的，CRO 的選擇，得到 - 推進協議統計數據的最終確定和選擇臨床站點是我們現在正在積極做的事情。所以這是我們即將成立的諮詢委員會的一個關鍵部分。

And Pam, can you also comment on the active versus the control in that trial. So it will be obviously nafamostat versus.

Pam，你能否也評論一下該試驗中的活性藥物與對照藥物。所以這顯然是 nafamostat 與。

Versus saline.

對抗生理鹽水。

Saline. and the primary end point over the first 24 hours is?

鹽水。前 24 小時內的主要終點是？

Activated clotting time. So it's basically a powerful anticoagulant versus saline and then looking at clotting time as your primary endpoint over the first 24 hours of the study. pretty straightforward.

活化凝血時間。所以它基本上是一種強大的抗凝血劑，而不是生理鹽水，然後在研究的前 24 小時內將凝血時間作為主要終點。非常簡單。

Got it. Yes. Well, I really appreciate all the details for being so looking forward to -- and just as 1 more question from us regarding the prefilled syringe products. Can you discuss any ongoing commercial path for a potential launch with the NDA closing? And also, just to clarify, PFS-01, so that's the first NDA to be submitted should we expect commercial launch of both prefilled syringe products or there will be market as soon as approved?

知道了。是的。好吧，我真的很感謝所有的細節讓我如此期待——還有一個關於預充式註射器產品的問題。您能否討論 NDA 關閉後可能推出的任何正在進行的商業路徑？而且，只是為了澄清，PFS-01，所以這是第一個提交的 NDA，我們應該期望這兩種預充式註射器產品的商業發布，還是一旦獲得批准就會有市場？

Yes. So the prefilled syringe products are being developed in a staggered fashion. The first one is the ephedrine or PFS-01 product. again, trade name or trademark right now as Fedsyra, ephedrine syringe, as you can imagine. So Fedsyra, something to that effect. So that will be on a 10-month review clock. During that period of time, we'll be discussing contracting with the IDNs as well as the group purchasing organizations. We're really encouraged by the uptake we've seen in the market of what I'll call similar, but potentially less advantageous products.

是的。因此，預充式註射器產品正在以交錯的方式開發。第一個是麻黃鹼或 PFS-01 產品。同樣，商品名稱或商標現在是 Fedsyra，麻黃鹼注射器，正如您想像的那樣。所以 Fedsyra，類似的東西。所以這將是一個為期 10 個月的審查時鐘。在那段時間裡，我們將討論與 IDN 以及團購組織的合同。我們在市場上看到我稱之為類似但可能不太有利的產品，這讓我們感到非常鼓舞。

And what do I mean by that? We mentioned in the script that and following the most recent launch of an ephedrine ready-to-use vial not in syringe form, but in the vial. So they still have to draw it up, having prepared to the table. And if they don't use it, they're going to have to discard it, which is significant waste. So it requires time, energy and potential waste is on -- or completed $30 million in sales in only its second year of launch. So there's clearly a need to advance the efficiency safety and quality of this product, in particular in this market. And so we're going to try to submit that here in very short order and get on that 10-month clock.

那是什麼意思？我們在腳本中提到，在最近推出的麻黃鹼即用型小瓶中，不是注射器形式，而是在小瓶中。所以他們仍然需要起草它，準備好擺在桌面上。如果他們不使用它，他們將不得不丟棄它，這是一種巨大的浪費。因此它需要時間、精力和潛在的浪費——或者僅在推出的第二年就完成了 3000 萬美元的銷售額。因此，顯然需要提高該產品的效率、安全性和質量，尤其是在這個市場上。因此，我們將嘗試以非常短的順序在這裡提交它，並在 10 個月的時間內完成。

The balance of the prefilled syringe that you're asking would be the phenylephrine. We're continuing to do work on that with Aguettant. It will be a staggered submission, so it will be delayed to after ephedrine. That will do 2 things for us, allow us to get a read from the FDA on ephedrine, which we feel very confident in and continue to work on development to fine-tune that submission as well.

你問的預裝注射器的餘額是去氧腎上腺素。我們將繼續與 Aguettant 合作。這將是一個交錯的提交，所以它會延遲到麻黃鹼之後。這將為我們做兩件事，使我們能夠從 FDA 那裡獲得關於麻黃鹼的信息，我們對此非常有信心，並繼續致力於開發以微調該提交。

The next question comes from James Molloy with Alliance Global Partners.

下一個問題來自 Alliance Global Partners 的 James Molloy。

This is actually Laura calling in for James Molloy. And also, congratulations on the recent divestment with DSUVIA with Alora Pharma. And with this, do you think you could possibly walk through your expectations for the ramp-up of sales? And then also, I have another question. So in regard to your Niyad, when do you expect the registrational trial to be commenced and then the expected study design that you're expecting to hold at this year?

這實際上是 Laura 為 James Molloy 打電話。此外，祝賀最近與 Alora Pharma 撤資 DSUVIA 。有了這個，你認為你可以實現你對銷售增長的期望嗎？然後，我還有另一個問題。那麼關於您的 Niyad，您預計什麼時候開始註冊試驗，然後是您希望在今年進行的預期研究設計？

Sure, Laura. So we can't comment on the ramp-up of sales. I think you were referring to DSUVIA on that 1 based off its divestment to Alora. What I can tell you is we are in deep transfer mode with them or transition mode between our commercial team, their commercial team. As a matter of fact, they're absorbing our commercial personnel, all except one to maintain the momentum we have in the procedural suites. I know that they will be expanding and training even further their hospital sales team based off their communication to us and they've got deep distribution. So we're excited about what they're going to do. I can't comment on a forecast from them, I can only comment on their commitment and resources that they're putting against it, which is impressive.

當然，勞拉。所以我們不能評論銷售的增長。我認為你指的是基於 DSUVIA 撤資給 Alora 的 1。我可以告訴你的是，我們與他們處於深度轉移模式，或者我們的商業團隊與他們的商業團隊之間處於過渡模式。事實上，他們正在吸納我們的商業人員，除了一個人以外，其他人員都是為了保持我們在程序套件中的勢頭。我知道他們將根據與我們的溝通進一步擴大和培訓他們的醫院銷售團隊，並且他們有深入的分銷。所以我們對他們將要做的事情感到興奮。我不能對他們的預測發表評論，我只能評論他們為此付出的承諾和資源，這令人印象深刻。

As it relates to Niyad, again, we mentioned that the study design has been agreed upon with the FDA. The end points have been agreed upon with the FDA. Those endpoints as a primary or activated clotting time. And as a secondary that we didn't mention are?

由於與 Niyad 相關，我們再次提到研究設計已與 FDA 達成一致。終點已與 FDA 達成一致。這些終點作為主要或激活的凝血時間。作為我們沒有提到的次要因素是什麼？

Yes, they're looking at basically the filter life span -- so we anticipate, obviously, when you're profusing saline into the circuit and you're not inhibiting (inaudible) that those filters lot much more frequently. And they're also looking at platelets, a number of transfusions how efficient the dialysis is looking at urea concentrations, et cetera.

是的，他們主要關注的是過濾器的使用壽命——所以我們預計，很明顯，當你在電路中大量注入鹽水並且你沒有抑制（聽不清）這些過濾器會更頻繁地使用。他們還在研究血小板、大量輸血、透析的效率如何以及尿素濃度等等。

So there's just a whole host of key secondary endpoints that are clinically important, but the primary end point again being activated clotting time over the first 24 hours of a powerful anticoagulant versus placebo, we feel pretty confident in that.

因此，只有一大堆關鍵的次要終點在臨床上很重要，但主要終點再次被激活，在強效抗凝劑與安慰劑的前 24 小時內凝血時間，我們對此非常有信心。

And I think you asked about timing, Laura. Again, we're just guiding to the second half of this year. Dr. Palmer team are working with the CROs as we sit here now based off of selection sites, et cetera. So again, we're excited to get that one going as quickly as we can.

我想你問過時間問題，勞拉。同樣，我們只是指導今年下半年。 Palmer 博士團隊正在與 CRO 合作，因為我們現在坐在這裡，基於選擇地點等。因此，我們再次很高興能盡快完成這項工作。

This concludes our question-and-answer session. I would like to turn the conference back over to Vince Angotti for any closing remarks.

我們的問答環節到此結束。我想將會議轉回給 Vince Angotti 作閉幕詞。

Thanks, Andrew, and thank you for all of you for joining us today and for your continued support of AcelRx. We're really excited about our execution on the stated plan. the significant progress we continue to make with Niyad and our prefilled syringes, in particular, Fedsyra. And we look and remain focused on driving long-term shareholder value with advancing this high-value, late-stage pipeline. I look forward to answering any additional questions you might have offline and sharing our future developments with you. Again, thank you for your attendance, and please be safe.

謝謝，安德魯，感謝你們所有人今天加入我們，感謝你們對 AcelRx 的持續支持。我們對執行既定計劃感到非常興奮。我們在 Niyad 和我們的預充式註射器（尤其是 Fedsyra）方面繼續取得的重大進展。我們期待並繼續專注於通過推進這一高價值的後期管道來推動長期股東價值。我期待著回答您離線時可能提出的任何其他問題，並與您分享我們未來的發展。再次感謝您的出席，請注意安全。

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

會議現已結束。感謝您參加今天的演講。您現在可以斷開連接。