NRX Pharmaceuticals Inc (NRXP) 2025 Q1 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the at NRx Pharmaceuticals first-quarter 2025 earnings call. (Operator Instructions) This call is being recorded on Thursday, May 15, 2025.

女士、先生們，下午好，歡迎參加 NRx Pharmaceuticals 2025 年第一季財報電話會議。（操作員指示）此通話於 2025 年 5 月 15 日星期四錄製。

I would now like to turn the conference over to Matthew Duffy, Chief Business Officer. Please go ahead.

現在我想將會議交給首席商務官馬修·達菲 (Matthew Duffy)。請繼續。

Thank you, Andrew, and welcome, everyone. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under US federal securities laws. These statements are subject to risks and uncertainties that could cause results to differ materially from historical experience or present expectations. Additional information concerning factors that could cause actual results to differ from statements made on this call is contained in our periodic reports filed with the SEC.

謝謝你，安德魯，歡迎大家。在我們繼續電話會議之前，我想提醒大家，根據美國聯邦證券法，本次電話會議中所做的某些聲明屬於前瞻性聲明。這些聲明受風險和不確定性的影響，可能導致結果與歷史經驗或當前預期有重大差異。有關可能導致實際結果與本次電話會議中的陳述不同的因素的更多信息，包含在我們向美國證券交易委員會提交的定期報告中。

The forward-looking statements made during this call speak only as of the date hereof. And the company undertakes no obligation to update or revise the forward-looking statements. Information presented on this call is contained in the press release issued today in the company's Form 10-Q, may be accessed from the Investor page of the NRx pharmaceuticals website.

本次電話會議中所做的前瞻性陳述僅代表截至本次電話會議當天的觀點。且本公司不承擔更新或修改前瞻性陳述的義務。本次電話會議中提供的資訊包含在該公司今天發布的 10-Q 表新聞稿中，可從 NRx 製藥網站的投資者頁面存取。

Joining me today on the call are Jonathan Javitt, our Founder, Chairman and CEO; and Michael Abrams, our Chief Financial Officer. Dr. Javitt will provide an overview of our company's progress as reported in today's Form 10-Q filing, which Mike will review our company's financial results. Following their prepared remarks, we will address investor questions.

今天與我一起參加電話會議的還有我們的創始人、董事長兼首席執行官喬納森·賈維特 (Jonathan Javitt)；以及我們的首席財務官邁克爾·艾布拉姆斯（Michael Abrams）。Javitt 博士將概述我們公司在今天的 10-Q 表格文件中報告的進展情況，Mike 將審查我們公司的財務結果。在他們發表準備好的發言之後，我們將回答投資人的問題。

I will now turn the call over to Jonathan. Jonathan?

現在我將把電話轉給喬納森。喬納森？

Thank you, Matt. Good evening, everyone, and thank you for joining us. NRx has had an exceptional start to 2025 with important advances across each of our programs.

謝謝你，馬特。大家晚上好，感謝大家的收看。NRx 在 2025 年取得了非凡的開端，我們的每個專案都取得了重要進展。

Suicidality remains a national epidemic. Approximately 13 million Americans seriously consider suicide every year, and 3.8 million of those make an active plan to do so according to the CDC. An American die from suicide every 11 minutes, and worldwide somebody said every minute. These appalling statistics drive our mission.

自殺傾向依然是全國性的流行病。根據美國疾病管制與預防中心統計，每年約有 1,300 萬美國人認真考慮自殺，其中 380 萬人制定了積極的自殺計畫。每 11 分鐘就有一名美國人自殺身亡，而全世界每分鐘就有一人自殺身亡。這些令人震驚的統計數據推動了我們的使命。

We've advanced our lead candidate, NRX-100 and NRX-101, in the regulatory process with FDA. We've taken concrete steps toward establishing the HOPE Therapeutics clinic network across the United States. We've also substantially reduced our corporate expenses. We're ending our quarter with more cash on the balance sheet than in prior quarters. We have capital on the balance sheet for the end of the year and anticipate clinic revenue well before. Clinic acquisition is being financed in a manner that does not require dilution of NRx stock.

我們已經推進了我們的主要候選藥物 NRX-100 和 NRX-101 的 FDA 監管流程。我們已採取具體措施，在全美範圍內建立 HOPE Therapeutics 診所網絡。我們也大幅削減了公司開支。本季末，我們的資產負債表上的現金比前幾季更多。我們在年底的資產負債表上有資本，並且預計診所的收入會提前到來。診所收購的融資方式不需要稀釋 NRx 股票。

The founding of NRx is based on our mission to help patients and caregivers address our country's national epidemic of suicidality, depression, PTSD and related disorders. We aim to do so with innovative medicines and now with HOPE Therapeutics to offer direct patient care for these legal conditions. Our mission has not changed. Importantly, we've accelerated our path to revenue with all three of our lead programs having potential to generate revenue in the foreseeable future.

NRx 的成立是基於我們的使命，即幫助患者和照護者解決我國普遍存在的自殺、憂鬱、創傷後壓力症候群和相關疾病問題。我們的目標是透過創新藥物來實現這一目標，現在我們與 HOPE Therapeutics 合作，為這些合法疾病的患者提供直接護理。我們的使命沒有改變。重要的是，我們加快了創收步伐，我們的三個主要項目均有可能在可預見的未來產生收入。

This extraordinary progress has been facilitated by the dedicated team at NRx and HOPE, as well as our committed investors. I'd like to take a moment to thank everyone for their tremendous efforts and support. Our timing is fortuitous as well. The US government, and in particular, the new administration has increased focus on treatment of suicidal depression and PTSD with particular emphasis on our military and veteran's communities.

這項非凡的進步得益於 NRx 和 HOPE 的專業團隊以及我們忠誠的投資者。我想藉此機會感謝大家的巨大努力和支持。我們的時機也是偶然的。美國政府，特別是新政府更加重視自殺性憂鬱症和創傷後壓力症候群的治療，特別強調我們的軍隊和退伍軍人社群。

Two weeks ago in the televised White House cabinet meeting, the president asked VA Secretary Collins what was being done to address suicide in veterans. The secretary's response included the need for psychedelic therapy. Ketamine, a drug we are developing, is one such therapy. The secretary of health and other members of the administration have specifically endorsed our class of medicines, as well as clinical approaches that are central to our business.

兩週前，在電視直播的白宮內閣會議上，總統詢問退伍軍人事務部部長柯林斯正在採取哪些措施來解決退伍軍人自殺問題。國務卿的回應包括迷幻療法的必要性。我們正在開發的一種藥物氯胺酮就是這樣一種療法。衛生部長和其他政府成員特別認可我們的藥品類別以及對我們的業務至關重要的臨床方法。

NRx has two separate operating groups: NRx Pharmaceutical, a traditional biotech drug development company with multi-billion-dollar opportunities; and HOPE Therapeutics, our patient care company, currently a wholly owned subsidiary, that is expected to be revenue generating, profitable in the near term, and ultimately spun out as its own company.

NRx 有兩個獨立的營運集團：NRx Pharmaceutical，一家擁有數十億美元商機的傳統生物技術藥物開發公司； HOPE Therapeutics 是我們的患者護理公司，目前是一家全資子公司，預計將在短期內產生收入並盈利，並最終分拆為獨立的公司。

With NRx, we have initiated filing of a new drug application, or NDA, for NRX-100, our preservative-free intravenous ketamine for the treatment of suicidal depression. There are no medicines approved to help people with this condition. We aim to change that this year.

我們與 NRx 合作，開始為 NRX-100 提交新藥申請（NDA），NRX-100 是一種用於治療自殺性憂鬱症的無防腐劑靜脈注射氯胺酮。目前尚無任何藥物已被批准用於治療這種疾病。我們的目標是今年改變這種狀況。

The application is supported by data from four well-controlled clinical trials, showing that the preferred dosing of ketamine has strong statistical efficacy compared to placebo, to active comparators such as midazolam, and to electroshock therapy. No other drug in history has demonstrated efficacy that meets or exceeds that of ECT without the debilitating memory loss and the other side effects of ECT.

該應用得到了四項嚴格控制的臨床試驗數據的支持，結果表明，與安慰劑、咪達唑侖等活性對照劑以及電擊療法相比，氯胺酮的優選劑量具有很強的統計功效。歷史上，沒有其他藥物能夠顯示出與 ECT 同等或超過 ECT 的療效，且不會引起嚴重的記憶喪失和 ECT 的其他副作用。

The FDA new drug application is further supported by stability data that now support three years of labeled-room temperature shelf stability, the maximum allowed by FDA. To protect NRX-100 exclusivity, this month, we filed a patent for our novel preservative-free formulation of NRX-100 with the US Patent and Trademark Office, potentially protecting our ketamine product into 2045 with a potential Orange Book listing.

FDA 新藥申請得到了穩定性數據的進一步支持，目前數據支持三年的標示室溫貨架穩定性，這是 FDA 允許的最長期限。為了保護 NRX-100 的獨家經營權，本月，我們向美國專利商標局申請了我們新型無防腐劑配方 NRX-100 的專利，有可能將我們的氯胺酮產品保護到 2045 年，並​​有可能將其列入橙皮書。

Crucially for Americans and the disproportionately impacted veteran and war fighter communities, together with first responders and others who suffer from this condition, we have manufacturing capacity to supply more than 1 million doses a month should we gain FDA approval.

對於美國人和受影響最大的退伍軍人和作戰人員群體，以及急救人員和其他患有這種疾病的人來說，至關重要的是，如果我們獲得 FDA 的批准，我們有能力每月供應超過 100 萬劑。

Because of our success in achieving long-term stability for preservative-free ketamine, we are also filing an abbreviated new drug application, or aNDA, for this product because of the administration's new focus on eliminating toxic substances, such as preservatives and dyes from the food and drug supply. The benzethonium chloride family of preservatives currently used in all commercial forms of ketamine has been shown to be neurotoxic and also toxic to epithelial cells. Now that we've shown there's no need for that preservative in the setting of modern drug manufacturing, we have the potential to deliver a ketamine-based product for all current uses of ketamine, not just to treat psychiatric conditions.

由於我們成功實現了無防腐劑氯胺酮的長期穩定性，我們也為該產品提交了一份簡化新藥申請（aNDA），因為政府現在將重點放在從食品和藥品供應中消除防腐劑和染料等有毒物質。目前所有商業形式的氯胺酮中使用的芐索氯銨類防腐劑已被證明具有神經毒性，並且對上皮細胞也有毒性。現在我們已經證明在現代藥物製造環境中不需要這種防腐劑，我們有可能為氯胺酮的所有當前用途提供基於氯胺酮的產品，而不僅僅是用於治療精神疾病。

In parallel, we're preparing a new drug application requesting accelerated approval for NRX-101. Our fixed dose oral combination of D-cycloserine and lurasidone for the treatment of suicidal depression in patients with suicidality or akathisia with the anticipation that we will initiate the filing in the current quarter.

同時，我們正在準備一份新藥申請，請求加速批准 NRX-101。我們的固定劑量口服組合藥物 D-環絲氨酸和魯拉西酮用於治療有自殺傾向或靜坐不能症患者的自殺性抑鬱症，預計我們將在本季度開始提交申請。

NRX-101 is the only antidepressant ever shown to decrease akathisia compared to standard-of-care antidepressants. Akathisia is the side effect of all previously marketed antidepressants, most closely associated with suicidality. In our clinical trial, NRX-101 was also associated with a more rapid resolution of suicidal ideation than the standard-of-care antidepressants.

NRX-101 是唯一一種與標準抗憂鬱藥物相比能夠降低靜坐不能的抗憂鬱藥物。靜坐不能是所有先前上市的抗憂鬱藥物的副作用，與自殺傾向最為密切相關。在我們的臨床試驗中，NRX-101 也與標準抗憂鬱藥物相比更快消除自殺意念有關。

Last year, we organized HOPE Therapeutics, a wholly owned subsidiary, in order to develop a national network of clinics to provide treatment directly to patients with suicidality, depression, PTSD, and other life-threatening conditions. These clinics focus on delivering integrated neuroplastic therapies, all under one safe, reliable umbrella. Although people talk about psychedelic drugs, focusing on the hallucinations that may be a side effect of many drugs in the class, science continues to teach us that these drugs work by stimulating the brain to form new connections or synapses, a process known as neuroplasticity.

去年，我們成立了全資子公司 HOPE Therapeutics，旨在建立一個全國性的診所網絡，直接為有自殺傾向、憂鬱症、創傷後壓力症候群和其他危及生命的疾病的患者提供治療。這些診所專注於提供全面神經可塑性療法，所有療法均在一個安全可靠的框架下進行。儘管人們談論迷幻藥時，重點關注的是該類藥物可能產生的副作用——幻覺，但科學不斷告訴我們，這些藥物透過刺激大腦形成新的連結或突觸來發揮作用，這個過程被稱為神經可塑性。

New treatments such as transcranial magnetic stimulation or TMS and some forms of hyperbaric therapy also have neuroplastic effects. The treatment paradigm for these diseases is rapidly evolving, and we intend to be on the forefront of that paradigm. The totality of evidence as we see it suggests that no one treatment can dependably yield the long-term remission from a disease that claims the lives of well over 50,000 Americans each year.

經顱磁刺激或 TMS 等新療法以及某些形式的高壓療法也具有神經可塑性作用。這些疾病的治療模式正在迅速發展，我們打算走在該模式的前沿。我們看到的所有證據表明，沒有一種治療方法能夠可靠地長期緩解這種每年奪走超過 50,000 美國人生命的疾病。

The clinical data, along with practitioners' experience, suggest that most patients contacting interventional psychiatry clinics for care will require a combination of NMDA antagonist drugs plus additional neuroplastic therapies, such as TMS and/or digital therapeutics in order to achieve long-term remission. These approaches are believed to work by raising the level of glutamate and other chemicals in the brain and causing the brain to form new healthy connections.

臨床數據以及從業人員的經驗表明，大多數聯繫介入性精神病診所接受治療的患者需要結合 NMDA 拮抗劑藥物和額外的神經可塑性療法（例如 TMS 和/或數位療法）才能實現長期緩解。人們認為這些方法透過提高大腦中的谷氨酸和其他化學物質的水平並使大腦形成新的健康連接而發揮作用。

As we become increasingly familiar with pioneers in the field, we routinely hear that as isolated therapies, a 60% or so remission from suicidal depression and PTSD can be seen. However, when therapies are integrated, some practitioners believe they're seeing sustained remission rates approaching 90%. The fact that successful clinics are able to provide patients with integrated care continue to grow, as distinct from the pump-up ketamine clinics that come and go, tells us that patients and their families embrace this model.

隨著我們越來越熟悉該領域的先驅者，我們經常聽說，作為單獨的療法，自殺性憂鬱症和創傷後壓力症候群的緩解率可達 60% 左右。然而，當綜合治療時，一些醫生相信他們看到的持續緩解率接近 90%。成功的診所能夠為患者提供全面護理，並且數量不斷增長，這與來來去去的氯胺酮診所截然不同，這告訴我們患者及其家人都接受這種模式。

HOPE has signed purchase agreements and a binding letter of intent to acquire three state-of-the-art interventional psychiatry practices: Kadima Neuroscience Institute in La Jolla; Dura Medical in Southwest Florida; and Neurospa TMS in the Tampa Bay area of Florida. The expansion in pipeline includes a number of additional clinics in Florida, the Mid-Atlantic and Midwest with whom we are in discussion for active negotiation.

HOPE 已簽署購買協議和具有約束力的意向書，以收購三家最先進的介入精神病學機構：位於拉霍亞的 Kadima 神經科學研究所；位於佛羅裡達州西南部的 Dura Medical；以及佛羅裡達州坦帕灣地區的 Neurospa TMS。正在擴建的診所包括佛羅裡達州、大西洋中部地區和中西部地區的一些其他診所，我們正在與這些診所進行積極的談判。

We continue to navigate the complexities of purchasing medical treatment facilities under state regulations as we move forward to closing and consummating these transactions. As reported earlier, HOPE signed a term sheet with Universal Capital, a global investment firm, for $7.8 million in debt facility to fund HOPE's growth and acquisition strategy. This, in addition to the previously announced term sheet with the strategic investor, brings $10.3 million in expected capital to HOPE in the coming weeks, providing sufficient resources for clinic acquisition and growth in a manner that is anticipated to be non-dilutive to shareholders of NRx stock.

在完成這些交易的過程中，我們將繼續根據國家法規處理購買醫療設施的複雜問題。根據先前通報，HOPE 與全球投資公司 Universal Capital 簽署了一份條款清單，以 780 萬美元的債務融資為 HOPE 的成長和收購策略提供資金。加上先前與策略投資者宣布的條款清單，這項交易將在未來幾週為 HOPE 帶來 1,030 萬美元的預期資本，為診所的收購和成長提供充足的資源，預計不會對 NRx 股票股東造成稀釋。

As you can see, we're making important progress building NRx into a company that will bring life-saving treatment to patients and financial returns to our investors. Shareholders routinely ask us when and why we expect to become a revenue-generating company. We believe that if we continue to execute according to plan, we'll be able to offer our proprietary ketamine drug, NRX-100, to the marketplace by early next year.

如您所見，我們在將 NRx 打造成為一家能夠為患者帶來救命治療並為投資者帶來財務回報的公司方面取得了重要進展。股東經常詢問我們何時以及為什麼我們預計會成為一家創收公司。我們相信，如果我們繼續按計劃執行，我們將能夠在明年年初向市場推出我們的專有氯胺酮藥物 NRX-100。

Ketamine, for example, is available today almost exclusively to those who can afford to pay out of pocket. It will remain so until FDA approval for ketamine to treat suicidal depression is obtained. We've initiated filing our NDA for NRX-100, the intravenous preservative-free ketamine for treatment of suicidal depression. And as noted, the NDA is supported with powerful efficacy data from multiple well-controlled trials, accelerated stability data sufficient to support a three-year shelf life, and an already filed manufacturing module.

例如，如今氯胺酮幾乎只提供給那些有能力自掏腰包的人。在 FDA 批准使用氯胺酮治療自殺性憂鬱症之前，這種情況將持續下去。我們已開始提交 NRX-100 的保密申請，NRX-100 是一種用於治療自殺性憂鬱症的靜脈注射無防腐劑氯胺酮。如上所述，NDA 得到了多個控制良好的試驗的強大功效數據、足以支持三年保質期的加速穩定性數據以及已提交的製造模組的支持。

Once filed, we expect receiving a PDUFA date from the FDA for later this year. Long-term ketamine safety is an issue that we believe will receive increased attention in the future as clinician prescribing and patient acceptance of ketamine becomes more widespread. They are data available not just from primate studies but from human studies as well that show repeated ketamine doses on the order of 60 doses or more of its currently available commercial formulations of intravenous ketamine may be toxic to the brain.

一旦提交申請，我們預計將於今年稍後收到 FDA 的 PDUFA 日期。我們相信，隨著臨床醫生開立的氯胺酮處方越來越廣泛以及患者對氯胺酮的接受度越來越高，長期氯胺酮安全性問題將在未來受到越來越多的關注。這些數據不僅來自靈長類動物研究，也來自人類研究，顯示重複注射氯胺酮（大約 60 劑或更多目前可用的商業配方靜脈注射氯胺酮）可能會對大腦產生毒性。

Repeated ketamine use is associated with damage to the urinary tract and bladder. The currently available ketamine preparation was designed in the 1970s in a multi-use vial in order for the product to be used in anesthesia. This multi-dose vial was anticipated to be drawn for multiple doses in various patients, necessitating the addition of a preservative.

反覆使用氯胺酮會導致泌尿道和膀胱損害。目前可用的氯胺酮製劑是 20 世紀 70 年代設計的多用途小瓶，以便用於麻醉。預計該多劑量藥瓶將為不同的患者抽取多劑量，因此需要添加防腐劑。

Back in the 1960s when this preparation was formulated, they used a potentially toxic preservative, benzethonium chloride. While there's no evidence that benzothonium chloride is toxic at its current concentration for the intended one-time use in anesthesia, its safety has never been shown or even proposed for repeated use.

早在 1960 年代配製這種製劑時，他們就使用了一種具有潛在毒性的防腐劑—芐索氯銨。雖然沒有證據表明苯並氯銨在目前的濃度下一次性用於麻醉會產生毒性，但其安全性從未得到證實，甚至從未被提議重複使用。

Indeed, the manufacturers of benzothonium chloride identify it as caustic, toxic, and capable of causing severe burns. This class of preservatives has already been removed from many eye drop formulations because of clear evidence of toxicity to the cornea and conjunctiva, even at the currently allowed levels.

事實上，苯扎氯銨的製造商認定它具有腐蝕性、毒性，並且能夠造成嚴重燒傷。由於有明顯證據表明即使在目前允許的水平下也會對角膜和結膜產生毒性，因此此類防腐劑已從許多眼藥水配方中去除。

Chronic use of ketamine is associated with development of ulcerative cystitis, potentially a dangerous bladder condition. This condition may be caused by the excretion of the preservative rather than by ketamine itself. We also note that we are not aware of any cases of interstitial cystitis reported following the use of Spravato, a nasal form of S-ketamine that does not contain benzothonium chloride. Accordingly, we're filing a citizen's petition with the FDA to remove ketamine preparations with benzothonium chloride from the market, given that this substance is now shown to be unnecessary for stability and sterility of ketamine.

長期使用氯胺酮會導致潰瘍性膀胱炎，這是一種潛在的危險膀胱疾病。這種情況可能是由防腐劑的排泄而不是氯胺酮本身引起的。我們也注意到，我們尚未發現任何在使用 Spravato（一種不含苯扎氯銨的 S-氯胺酮鼻腔劑型）後報告出現間質性膀胱炎的病例。因此，我們向 FDA 提交了一份公民請願書，要求將含有苯並氯銨的氯胺酮製劑從市場上撤出，因為現在已證明這種物質對於氯胺酮的穩定性和無菌性來說是不必要的。

The company also plans to file an abbreviated NDA or aNDA for preservative-free ketamine so that this drug can be used as broadly as possible. Although we'll never lose sight of our core mission to treat lethal CNS diseases, including suicidal depression and PTSD, the market for NRX-100 may be far larger than originally anticipated based on the current scenario.

該公司還計劃為不含防腐劑的氯胺酮提交一份簡化的 NDA 或 aNDA，以便該藥物盡可能廣泛地使用。儘管我們永遠不會忘記治療致命中樞神經系統疾病（包括自殺性憂鬱症和創傷後壓力症候群）的核心使命，但根據目前的情況，NRX-100 的市場可能比最初預期的要大得多。

As I discussed previously, we have current manufacturing capacity to supply 1 million vials of ketamine each month. We also have potential to scale up capacity if needed. As noted, we have taken steps to protect our preservative-free formulation with the filing of a patent that has the potential to protect the product into 2045.

正如我之前所討論的，我們目前的生產能力是每月供應 100 萬瓶氯胺酮。如果需要，我們還有潛力擴大產能。如上所述，我們已採取措施保護我們的無防腐劑配方，並申請了專利，該專利有可能將產品保護到 2045 年。

The toxic preservative is not the only challenge associated with currently available 60-year-old ketamine formulation. As produced, ketamine hydrochloride has a pH of less than 4. This isn't a problem for intravenous use where it's diluted. But precludes subcutaneous administration as dosing of any drug with this pH can cause pain and even cause skin ulcers. If you try to raise the pH of the current ketamine formulation, the ketamine precipitates out of solution, rendering it unusable.

有毒防腐劑並不是目前已有 60 年歷史的氯胺酮配方面臨的唯一挑戰。產生的鹽酸氯胺酮的 pH 值小於 4。對於稀釋後的靜脈注射來說，這不是問題。但排除皮下給藥，因為任何具有這種 pH 值的藥物的劑量都會引起疼痛，甚至導致皮膚潰瘍。如果您嘗試提高目前氯胺酮配方的 PH 值，氯胺酮就會從溶液中沉澱出來，從而變得無法使用。

Further, administration challenges face those who've tried to give it by now. So aside from the obvious safety risks of unmonitored administration of a schedule-free drug, people have learned that the resulting blood levels from oral ketamine administration are highly inconsistent. Similar products have occurred with ketamine intranasal spray.

此外，那些試圖給予幫助的人現在還面臨管理挑戰。因此，除了不受監控地使用不受計劃約束的藥物所帶來的明顯安全風險之外，人們還了解到口服氯胺酮所產生的血液濃度高度不一致。類似的產品還有氯胺酮鼻內噴劑。

While intravenous administration is completely reliable in achieving the blood levels, this requires skilled nurses in clinic facilities. With these challenges to administration, we hope to offer an attractive alternative, subcutaneous ketamine delivered in the same way that insulin and newer obesity drugs are given. However, this route of administration is only possible with a pH neutral form of ketamine. We've now developed that patentable version of pH neutral ketamine, one that remains stable at room temperature and is expected to begin human bioequivalence trials this year.

雖然靜脈注射可以完全可靠地達到血液水平，但這需要診所裡熟練的護士。面對這些管理挑戰，我們希望提供一種有吸引力的替代方案，以與胰島素和新型減肥藥物相同的方式皮下注射氯胺酮。然而，這種給藥途徑僅對 pH 值中性的氯胺酮才有可能。我們現在已經開發出可獲得專利的 pH 中性氯胺酮，它在室溫下保持穩定，預計今年將開始人體生物等效性試驗。

As is well known, bioequivalence is far simpler and less expensive to prove than safety and efficacy. Our goal in gaining FDA approval for NRX-100 is to significantly expand the number of patients who have access to the benefit from this important treatment. The current off-label use of ketamine and CNS disorders is generally only available to patients who can pay out of pocket because insurance companies do not pay for unlabeled treatments. We expect NRX-100, once approved, to be widely reimbursed, thus providing access for the vast majority of people in need, not just those with means to spend thousands of dollars in cash for treatment.

眾所周知，生物等效性的證明比安全性和有效性的證明要簡單得多，而且成本也低得多。我們獲得 FDA 對 NRX-100 的批准的目標是大幅增加能夠從這項重要治療中受益的患者數量。目前，氯胺酮和中樞神經系統疾病的未列入藥品說明書的使用通常只適用於那些能夠自掏腰包的患者，因為保險公司不支付未列入藥品說明書的治療費用。我們預計，NRX-100 一旦獲得批准，將得到廣泛的報銷，從而為絕大多數有需要的人提供治療機會，而不僅僅是那些有能力花費數千美元現金進行治療的人。

NRX-100 represents a major opportunity for our company. The current market for intranasal ketamine is significant. J&J recently released first-quarter 2025 sales data on Spravato and is on track to generate $1.3 billion in sales this year, all while the label states that Spravato has not demonstrated anti-suicidal properties. Thus NRX-100 represents the multi-billion-dollar opportunity for NRx, and we are getting closer and closer to providing this lifesaving opportunity to patients.

NRX-100 對我們公司來說是一個重大機會。目前鼻腔內氯胺酮的市場規模很大。強生公司最近發布了 Spravato 2025 年第一季的銷售數據，預計今年的銷售額將達到 13 億美元，但標籤上卻顯示 Spravato 並未顯示出抗自殺特性。因此，NRX-100 代表著 NRx 數十億美元的機會，我們也越來越接近為患者提供這項拯救生命的機會。

Let's now discuss our treatment for bipolar depression in patients with suicidality or akathisia, NRX-101. While bipolar depression affects approximately 7 million people in the US, people with bipolar depression, akathisia, or suicidality are at imminent risk of self-harm. There are no medications approved to treat these patients in the US. Current treatment options all carry the risk of suicide and akathisia, which are known side effects of serotonin-active antidepressants. These patients need better treatment options urgently.

現在讓我們討論一下針對有自殺傾向或靜坐不能症的雙相憂鬱症患者的治療方法，NRX-101。雖然雙相憂鬱症影響了美國約 700 萬人，但患有雙相憂鬱症、靜坐不能或自殺傾向的人面臨著自我傷害的迫在眉睫的風險。美國目前尚無批准用於治療這些患者的藥物。目前的治療方案都存在自殺和靜坐不能的風險，這是已知的血清素活性抗憂鬱藥物的副作用。這些患者迫切需要更好的治療選擇。

Today, the only approved FDA treatment, or the only FDA approved treatment, is electroshock therapy. NRX-101 is our oral combination of D-cycloserine, an NMDA receptor blocker, and lurasidone, the standard of care in bipolar depression. NRX-101 has the opportunity to offer a breakthrough in the care of patients with bipolar depression. In clinical trials, we've demonstrated comparable or greater antidepressant effect compared to the standard of care with a statistically significant improvement in the safety of NRX-101 due to a reduction in suicidality and akathisia.

如今，唯一獲得 FDA 批准的治療方法，或者說唯一獲得 FDA 批准的治療方法是電擊療法。NRX-101 是我們口服的 D-環絲胺酸（一種 NMDA 受體阻斷劑）和魯拉西酮（雙相憂鬱症的標準治療方法）的組合。NRX-101 有機會為雙極性憂鬱症患者的照護帶來突破。在臨床試驗中，我們證明了與標準治療相比，NRX-101 具有相當或更好的抗憂鬱效果，並且由於自殺傾向和靜坐不能的減少，其安全性在統計上顯著提高。

In our clinical trials, NRX-101 demonstrated strong antidepressant efficacy comparable to the standard of care with a more favorable safety profile, a recently completed Phase 2b/3 clinical trial of NRX-101 presented last May at the American Society of Clinical Psychopharmacology, demonstrated both a reduction in depression scores as well as symptoms of suicidality and is now the first oral antidepressant to reduce symptoms of akathisia compared to standard of care of potentially lethal side effects of nearly all antidepressants. This would represent a new paradigm for the treatment of bipolar depression, if approved.

在我們的臨床試驗中，NRX-101 表現出與標準治療相當的強大抗憂鬱功效，且具有更佳的安全性。去年 5 月在美國臨床精神藥理學會上發表的 NRX-101 2b/3 期臨床試驗結果顯示，該藥物既可以降低憂鬱評分，又可以減輕自殺症狀。目前，與幾乎所有抗憂鬱藥物都具有致命副作用的標準治療相比，NRX-101 是第一種可以減輕靜坐不能症狀的口服抗憂鬱藥物。如果獲得批准，這將代表治療雙相憂鬱症的新範例。

Akathisia is not commonly discussed as a side effect of serotonin-active medications. However, key opinion leaders and patients who've suffered from akathisia regard it as the worst side effect of these antidepressants. Patients frequently describe it as a feeling of jumping out of their skin. Patients with akathisia are known to jump off of roofs and in front of oncoming trains.

靜坐不能症通常不會被討論為血清素活性藥物的副作用。然而，關鍵意見領袖和患有靜坐不能症的患者認為這是這些抗憂鬱藥物最嚴重的副作用。患者經常將其描述為一種從皮膚裡跳出來的感覺。患有靜坐不能症的患者會從屋頂跳下並跳到迎面駛來的火車前。

In fact, in 2024, a petition at the British Columbia Supreme Court for the right to end her life rather than continue to suffer from akathisia. Currently, patients have no option other than simply enduring this side effect in order to achieve the critical antidepressant effects that are needed to control bipolar depression or choose to have electroshock therapy.

事實上，2024 年，她向不列顛哥倫比亞省最高法院提交了一份請願書，要求獲得結束生命的權利，而不是繼續遭受靜坐不能症的折磨。目前，患者除了忍受這種副作用以達到控制雙相憂鬱症所需的關鍵抗憂鬱效果或選擇電擊療法之外別無選擇。

The data we presented at ASCP confirms data from our earlier STABIL-B trial, demonstrating that NRX-101 is the first oral antidepressant that have effective antidepressant properties while simultaneously decreasing akathisia and suicidality. We believe this product profile could lead to NRX-101, becoming the drug of choice in bipolar depression.

我們在 ASCP 上展示的數據證實了我們早期 STABIL-B 試驗的數據，表明 NRX-101 是第一種具有有效抗憂鬱特性同時降低靜坐不能和自殺傾向的口服抗憂鬱藥物。我們相信該產品特性可能使 NRX-101 成為治療雙相憂鬱症的首選藥物。

We plan to initiate filing of our NDA for accelerated approval of NRX-101 for suicidal bipolar depression in patients at risk of akathisia or suicidality this quarter. With the lack of treatment options for this segment of people with bipolar depression and our strong data, we and our regulatory council believe this to be a vital unmet medical need and appropriate for consideration of accelerated approval. We anticipate a 2025 PDUFA date. Based on prevalence data, prescribing frequency of serotonin-active medications and bipolar depression, and the risk of akathisia, the company anticipates that the market for the initial indication is over $2 billion, while the broad bipolar market could markedly exceed $5 billion.

我們計劃於本季開始提交 NDA，以加速批准 NRX-101 用於治療患有靜坐不能或自殺風險的自殺性雙相憂鬱症患者。由於這部分患有躁鬱症的人缺乏治療選擇，而且我們擁有強大的數據，我們和我們的監管委員會認為，這是一個至關重要的未滿足的醫療需求，適合考慮加速批准。我們預計 PDUFA 日期為 2025 年。根據盛行率數據、血清素活性藥物和雙相憂鬱症的處方頻率以及靜坐不能的風險，該公司預計初始適應症的市場規模超過 20 億美元，而廣泛的雙相情感障礙市場規模可能顯著超過 50 億美元。

Since the beginning of the year, we've accelerated progress towards establishing the HOPE Therapeutics' Interventional Psychiatry Clinic Network. We've outlined our plan to establish and grow the HOPE network as a national and ultimately international network of interventional psychiatry centers. These centers would be designed to combine the latest neuroplastic treatments and protocols in an integrated and reproducible manner across the HOPE platform.

自今年年初以來，我們加快了建立 HOPE Therapeutics 介入精神科診所網絡的進程。我們已經制定了建立和發展 HOPE 網絡的計劃，使其成為一個全國性的、並最終成為國際性的介入精神病學中心網絡。這些中心將旨在透過 HOPE 平台以整合和可重複的方式結合最新的神經可塑性治療和方案。

The business model for HOPE Therapeutics is somewhat similar to that of DaVita, a company that was instrumental in making kidney dialysis reliable and reproducible in a manner that has transformed the industry and continued to reward its investors. So far in 2025, we've signed definitive purchase agreements to acquire Kadima Neuroscience Institute, pioneering interventional psychiatry clinic in La Jolla, California, and Dura Medical, an extraordinary clinic group in Southwest Florida. Further, we've executed a binding letter of intent with Neurospa TMS Holdings, a pioneer in TMS offerings to acquire their clinic group in the Tampa Bay area on the west coast of Florida.

HOPE Therapeutics 的商業模式與 DaVita 有點相似，DaVita 公司在使腎臟透析變得可靠和可重複方面發揮了重要作用，從而改變了整個行業並繼續為其投資者帶來回報。到 2025 年為止，我們已經簽署了最終購買協議，收購位於加州拉霍亞的先驅介入精神病學診所 Kadima 神經科學研究所和位於佛羅裡達州西南部的非凡診所集團 Dura Medical。此外，我們還與 TMS 產品的先驅 Neurospa TMS Holdings 簽署了具有約束力的意向書，以收購其位於佛羅裡達州西海岸坦帕灣地區的診所集團。

Our objective for the year is to create a ring of Hope Therapeutics Clinics that starts in Naples on the southwest coast runs through Tampa and Orlando back down to Miami. But these three clinics, collectively on a forward-looking revenue, are anticipated to represent $15 or more in annual revenue just on their own. Kadima's founder, Dr. David Feifel, has agreed to serve as HOPE's Chief Medical Innovation Officer, post-acquisition.

我們今年的目標是創建一個希望治療診所環線，從西南海岸的那不勒斯開始，穿過坦帕和奧蘭多，然後回到邁阿密。但就前瞻性收入而言，這三家診所預計每年的收入將達到 15 美元或更多。Kadima 的創辦人 David Feifel 博士已同意在收購後擔任 HOPE 的首席醫療創新長。

He's one of the first academic psychiatrists to move ketamine and TMS therapy to the community care model and is frequently featured in the national media, such as in Rolling Stone, on Peacock. He's one of their most knowledgeable experts on the safe and appropriate use of ketamine and other advanced therapies in mental health treatment. Some of you may have seen his recent interview with Dr. Sanjay Gupta.

他是首批將氯胺酮和 TMS 療法引入社區護理模式的學術精神病學家之一，並經常出現在國家媒體上，例如《滾石》雜誌和《孔雀》雜誌。他是他們在安全和適當使用氯胺酮和其他先進療法進行精神健康治療方面最有知識的專家之一。你們中的一些人可能已經看過他最近接受桑傑·古普塔博士的採訪。

Over the remaining months of 2025, we expect to announce the inclusion of additional EBITDA positive centers in the HOPE network. Looking at the market, we anticipate that the acquisition of 20 clinics, each with current revenue of approximately $5 million, will enable us to meet our forward-looking revenue targets. Looking ahead, these best-in-class clinics can generate operating margins of 30% or higher, with significant opportunities for future growth.

在 2025 年剩餘的幾個月裡，我們預計將宣佈在 HOPE 網路中納入更多 EBITDA 正值中心。放眼市場，我們預計收購 20 家診所（每家診所的當前收入約為 500 萬美元）將使我們能夠實現前瞻性的收入目標。展望未來，這些一流的診所可以產生 30% 或更高的營業利潤率，並具有巨大的未來成長機會。

On the financing front, HOPE has announced signing term sheets for more than $10 million in acquisition capital in the form of both debt and equity, to fuel our initial acquisitions with strong interest expressed by investors in continuing to support our roll-up strategy. As we've always said and as these term sheets illustrate, we continue to expect funding for HOPE to be independent of NRx stock and thus non-dilutive to NRx shareholders.

在融資方面，HOPE 已宣布簽署超過 1000 萬美元的收購資本條款清單，以債務和股權的形式提供資金，以支持我們的初步收購，投資者也表現出濃厚的興趣，將繼續支持我們的整合策略。正如我們一直所說的以及這些條款清單所表明的那樣，我們繼續預期 HOPE 的融資將獨立於 NRx 股票，因此不會稀釋 NRx 股東的權益。

Additionally, we expect that a portion of the earnings generated through HOPE may support NRx's path to profitability and our plan's spin-out of HOPE and subsequent listing on a national stock exchange will provide balance sheet value both to NRx and to its shareholders. As you can see in our 10-Q, we have substantially reduced operating expenses and are forecasting profitability on a going forward run rate basis by the end of 2025 with revenue and EBITDA from HOPE Therapeutics, along with potential sales of our medications.

此外，我們預計 HOPE 產生的部分收益可能支持 NRx 實現盈利，而我們計劃分拆 HOPE 並隨後在國家證券交易所上市將為 NRx 及其股東提供資產負債表價值。正如您在我們的 10-Q 中所看到的，我們大幅削減了營運費用，並預測到 2025 年底，憑藉 HOPE Therapeutics 的收入和 EBITDA 以及我們藥物的潛在銷售額，我們將在未來運行率基礎上實現盈利。

I'll now ask Mr. Michael Abrams, our CFO, to review our financial results from the first quarter of 2025. Mike?

現在，我請我們的財務長麥可‧艾布拉姆斯先生回顧我們 2025 年第一季的財務表現。麥克風？

Thank you, Jonathan. So three months ended March 31, 2025, the company reported a net loss to $5.5 million versus a net loss of $6.5 million for the comparable quarter in 2024 and a loss from operations of $3.8 million versus a loss from operations of $6 million for the comparable quarter in 2024.

謝謝你，喬納森。因此，截至 2025 年 3 月 31 日的三個月，該公司報告淨虧損為 550 萬美元，而 2024 年同期淨虧損為 650 萬美元，營業虧損為 380 萬美元，而 2024 年同期營業虧損為 600 萬美元。

Research and development and general administrative expenses were $0.8 million and $2.9 million as compared to $1.7 million and $4.3 million for the comparable quarter ended March 31, 2024, respectively. As of March 31, 2025, NRx Pharmaceuticals had approximately $5.5 million in cash and cash equivalents. The company believes that its current capital position combined with ongoing financing discussions and partnerships will support operations through at least the end of 2025. NRx continues to implement operational efficiencies to extend cash runway and maintain focus on our path to generating revenue and value for our shareholders.

研發和一般管理費用分別為 80 萬美元和 290 萬美元，而截至 2024 年 3 月 31 日的同期分別為 170 萬美元和 430 萬美元。截至 2025 年 3 月 31 日，NRx Pharmaceuticals 擁有約 550 萬美元的現金和現金等價物。該公司相信，其目前的資本狀況加上正在進行的融資談判和合作夥伴關係將支持至少 2025 年底的營運。NRx 繼續實施營運效率以延長現金流量並繼續專注於為股東創造收入和價值。

With that, I turn it back to Jonathan. Jonathan?

說完，我把它轉回給喬納森。喬納森？

Thank you, Mike. So we founded NRx with the goal of preventing and treating suicidality in patients with depression and PTSD. This is close to my heart and to the hearts of everybody who works with us. Our plan 2025 PDUFA date with two NDAs in this space and continuing the development of HOPE Therapeutics national network for care delivery are transformative steps for the company and for the treatment of mental health in the United States.

謝謝你，麥克。因此，我們成立了 NRx，目標是預防和治療憂鬱症和創傷後壓力症候群患者的自殺傾向。這是我以及與我們一起工作的每一個人的心頭之事。我們計劃在 2025 年簽署 PDUFA 協議，在該領域簽署兩份 NDA，並繼續開發 HOPE Therapeutics 全國醫療服務網絡，這對於公司和美國的精神健康治療來說都是變革性的一步。

I'd like to thank the NRx team, our investors, and most importantly, the patients who participated in our clinical trials for their steadfast support of our pursuit of this vision. We're ready to take questions from the audience.

我要感謝 NRx 團隊、我們的投資者，最重要的是，感謝參與我們臨床試驗的患者對我們追求這一願景的堅定支持。我們已準備好回答觀眾的提問。

(Operator Instructions) Tom Shrader, BTIG.

（操作員指示）Tom Shrader，BTIG。

Good afternoon. Congratulations on the whirlwind of progress. I had a remedial question on the recent IP. What does that buy you if in fact you get approved? And as far as I understand it, the IP you really care about is the pH neutral version. So just your thoughts on, one, how strong the patent application is to leave the preservative out? And two, how important is it for you to get that if you get approval? Thanks.

午安.恭喜你所取得的快速進步。我最近有一個關於IP的補習問題。如果您確實獲得批准，那會為您帶來什麼？據我了解，您真正關心的 IP 是 pH 中性版本。那麼，您認為，第一，專利申請的強度有多大，可以排除防腐劑？第二，如果獲得批准，這對您來說有多重要？謝謝。

Well, I would never make predictions about how strong any individual patent is. I know that the Patent Council filing the patent is highly experienced and strongly believes in the claims that we're filing with the USPTO.

好吧，我永遠不會預測任何單一專利有多強。我知道，申請專利的專利委員會經驗豐富，並且堅信我們向美國專利商標局提交的權利要求。

Why does it matter? It matters because, in our view, drugs with toxic preservatives are going to be withdrawn from the market. And if we're coming to market with an Orange Book patented form of ketamine, we potentially have market exclusivity for an extended period of time. We always said that ketamine was a generic drug. And by adding a new use, the maximum we were going to get was three years of data exclusivity under Paragraph 4 from the FDA.

這為什麼重要？這很重要，因為我們認為含有有毒防腐劑的藥物將會被撤出市場。如果我們將橙皮書專利形式的氯胺酮推向市場，我們可能會在較長時間內擁有市場獨佔權。我們總是說氯胺酮是一種仿製藥。透過增加新用途，我們最多可以根據 FDA 第 4 款獲得三年的資料獨佔權。

And then we kind of surprised ourselves. And it turns out that we may have much longer exclusivity on racemic ketamine in a preservative-free preparation than we originally anticipated. So if that happens, that's certainly good for our shareholders. The pH neutral form of ketamine is certainly proprietary, certainly patentable, and is expected to have long-term protection. But it turns out we may have longer-term protection than we ever predicted from a better version of old-fashioned racemic ketamine, given the focus of the current Secretary of Health and Human Services on getting toxic preservatives out of the food and drug supply.

然後我們自己都感到驚訝。事實證明，我們在無防腐劑製劑中對外消旋氯胺酮的獨佔期可能比我們最初預期的要長得多。如果發生這種情況，對我們的股東來說肯定是好事。pH 值中性的氯胺酮當然是專有的，當然可以獲得專利，並且有望獲得長期保護。但事實證明，考慮到現任衛生與公眾服務部部長致力於從食品和藥品供應中清除有毒防腐劑，我們可能從更好的老式外消旋氯胺酮中獲得比我們預期更長期的保護。

Good. Thank you. That's a useful answer. Thank you.

好的。謝謝。這是一個有用的答案。謝謝。

Ed Woo, Private investor.

Ed Woo，私人投資者。

Yes, I'm actually with Ascendian Capital. Congratulations on all the progress. And obviously, it's going to be a very exciting year for you guys. Have you given any consideration for NRX-100 and also HOPE that (inaudible) either be able to go internationally beyond the US?

是的，我實際上是在 Ascendian Capital 工作的。祝賀你取得的所有進展。顯然，對你們來說，這將會是個非常令人興奮的一年。您是否考慮過 NRX-100，並且希望（聽不清楚）能夠在美國以外走向國際？

Certainly, we intend to make NRX-100 available more broadly. European countries are actually more sensitive to toxic substances and foods and drugs than the United States historically has been. So if we're able to make this case in the US, we would anticipate that there is significant international potential for NRX-100. And in fact, we've been approached by a number of international entities for that specific purpose.

當然，我們打算讓 NRX-100 得到更廣泛的應用。事實上，歐洲國家對有毒物質、食品和藥物的敏感度比美國歷史上更高。因此，如果我們能夠在美國實現這一目標，我們預計 NRX-100 將具有巨大的國際潛力。事實上，許多國際實體已經就這一特定目的與我們聯繫。

Great, that sounds good. Thanks for answering my questions and I wish you guys good luck. Thank you.

太好了，聽起來不錯。謝謝你們回答我的問題並祝你們好運。謝謝。

There are no further questions at this time. Please proceed.

目前沒有其他問題。請繼續。

That's all the time we have for questions, folks. Thank you very much for joining us this evening. We're extremely excited about the year ahead with two potential drug approvals and a subsidiary targeting multiple large, profitable mental health clinics moving ahead. This concludes the NRx Pharmaceuticals first quarter 2025 results conference call. Thank you all for participating.

各位，我們的提問時間就到這裡了。非常感謝您今晚參加我們的活動。我們對未來一年感到非常興奮，因為有兩種潛在的藥物獲批，而且一家子公司正在瞄準多家大型、盈利的心理健康診所。NRx Pharmaceuticals 2025 年第一季業績電話會議到此結束。感謝大家的參與。

Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.

女士們、先生們，今天的電話會議到此結束。感謝您的參與，並請您斷開線路。