NRX Pharmaceuticals Inc (NRXP) 2023 Q3 法說會逐字稿

Thank you for standing by. This is the conference operator. Welcome to the NRX Pharmaceuticals third-quarter 2023 earnings conference call. As a reminder, all participants are in listen-only mode, and the conference is being recorded. (Operator Instructions)

謝謝你的支持。這是會議操作員。歡迎參加 NRX Pharmaceuticals 2023 年第三季財報電話會議。提醒一下，所有與會者都處於僅聽模式，並且正在錄製會議。 （操作員說明）

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

我現在想將會議交給首席商務官 Matthew Duffy。請繼續。

Thank you, [Ashia], 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 actual results to differ materially from historical precedent experience or present expectations. Additional information concerning factors that could cause actual results to differ from the statements made on this call is contained in our periodic reports filed with the SEC.

謝謝你，[Ashia]，歡迎大家。在我們進行電話會議之前，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陳述屬於前瞻性陳述。這些陳述存在風險和不確定性，可能導致實際結果與歷史先例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聲明不同的因素的更多資​​訊包含在我們向 SEC 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 yesterday and in the company's Form 10-Q that was filed earlier today, which may be accessed from the Investors page on the NRX Pharmaceuticals, Inc. website.

本次電話會議中所做的前瞻性陳述僅代表截至本新聞稿發布之日的情況，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昨天發布的新聞稿和今天早些時候提交的公司 10-Q 表格中，可以從 NRX Pharmaceuticals, Inc. 網站的投資者頁面訪問該表格。

Joining me on today's call are Stephen Willard, Chief Executive Officer; Dr. Jonathan Javitt, our Founder and Chief Scientist; and Richard Narido, Chief Financial Officer and Treasurer. Stephen and Jonathan will provide a summary of the company's progress, Rich will review the company's financial results, and then Stephen will review upcoming milestones before making closing comments. Following their prepared remarks, we will address investor questions.

與我一起參加今天電話會議的還有執行長 Stephen Willard；喬納森·賈維特博士，我們的創始人兼首席科學家；財務長兼財務主管理查德‧納裡多 (Richard Narido)。史蒂芬和喬納森將提供公司進展的摘要，里奇將審查公司的財務業績，然後史蒂芬將在發表總結評論之前審查即將到來的里程碑。在他們準備好的發言之後，我們將回答投資人的問題。

I'll now turn the call over to Stephen. Steve?

我現在將把電話轉給史蒂芬。史蒂夫？

Thank you, Matt. Good afternoon, everyone, and thank you for joining us. The third quarter represents a potential turning point for our company. As we are approaching our clinical trial enrollment goals for our partnered foundation product, NRX-101, while opening new clinical initiatives in chronic pain, urinary tract infection, and NRX-100 for suicidal depression.

謝謝你，馬特。大家下午好，感謝您加入我們。第三季是我們公司潛在的轉捩點。隨著我們正在接近我們的合作基礎產品 NRX-101 的臨床試驗註冊目標，同時在慢性疼痛、泌尿道感染和治療自殺性憂鬱症的 NRX-100 方面開展新的臨床計劃。

We expect four potential upcoming milestones. First, our core clinical trial of NRX-101 for treatment-resistant bipolar depression with suicidality. Second, the near-term readout of the Department of Defense funded clinical trials of D-cycloserine for chronic pain. Third, our program to seek a new drug approval for intravenous ketamine, which we have designated as NRX-100 and establish that drug in a new, freshly capitalized company that aims to be cash flow positive by year end 2024. And four, the near-term approval of our investigational new drug application and award of qualified infectious disease product classification to NRX-101 in complicated urinary tract infection, which is called cUTI.

我們預計即將出現四個潛在的里程碑。首先，我們的 NRX-101 治療具有自殺傾向的難治性雙相憂鬱症的核心臨床試驗。其次，國防部近期發表資助 D-環絲胺酸治療慢性疼痛的臨床試驗。第三，我們尋求靜脈注射氯胺酮新藥批准的計劃，我們將其指定為NRX-100，並在一家新資本化的新公司中建立該藥物，目標是到2024 年底實現正現金流。第四，近期的現金流量- NRX-101治療複雜性尿路感染（稱為cUTI）的研究新藥申請得到長期批准，並獲得合格的傳染病產品分類。

Achieving any one of those catalysts has the potential to unlock substantial shareholder value. Our success on more than one front has the potential to unlock exponential growth. I am incredibly proud of our team, our collaborators and partners, and most of all, the patients who have made such an important contribution to these efforts. All of us at NRX are deeply grateful to the many shareholders who have reached out to us, encourages us, and supported us for a period of immense challenge in the biotechnology market. Together, we are pursuing and NRX's goal of bringing hope to life on a daily basis.

實現這些催化劑中的任何一種都有可能釋放巨大的股東價值。我們在多個方面的成功有可能帶來指數級成長。我為我們的團隊、我們的合作者和合作夥伴，尤其是為這些努力做出如此重要貢獻的患者感到無比自豪。 NRX 的所有人都深深感謝許多股東，他們在生技市場面臨巨大挑戰的時期向我們伸出援手、鼓勵我們、支持我們。我們和 NRX 共同追求為日常生活帶來希望的目標。

Now, I would like to invite Dr. Jonathan Javitt, our Chief Scientist, to review our clinical development program.

現在，我想邀請我們的首席科學家喬納森·賈維特博士來回顧我們的臨床開發計劃。

Thank you, Steve. Let's lead off with our foundational program NRX-101 for suicidal bipolar depression. We restarted this program in March 2022 on the tail of the COVID pandemic. In the subsequent 18 months, we've transferred our manufacturing to the US, gained FDA alignment for our CMC and stability program, manufactured approximately 1 million capsules of NRX-101, and relaunched our clinical program.

謝謝你，史蒂夫。讓我們從治療自殺性雙極性憂鬱症的基礎計畫 NRX-101 開始。我們在 2022 年 3 月新冠疫情大流行結束後重新啟動了該計劃。在接下來的 18 個月中，我們將生產轉移到了美國，獲得了 FDA 對我們的 CMC 和穩定性計劃的認可，生產了大約 100 萬粒 NRX-101 膠囊，並重新啟動了我們的臨床計劃。

We're excited to announce today that the company is near completing enrollment of the originally targeted 70 patients in the Phase 2b/3 trial. I believe as of yesterday, the number was 69. We've decided to continue enrollment through the end of the month and to target 74 evaluable patients randomized to NRX-101 versus standard of care medicine.

我們今天很高興地宣布，該公司即將完成 2b/3 期試驗最初目標 70 名患者的招募。我相信截至昨天，這個數字是 69 人。我們決定在本月底繼續入組，並針對 74 名可評估患者隨機分配 NRX-101 與標準護理藥物。

The results of this trial have the potential to be used for registrational filing. Just target populations based on the company's January 2023 meeting with the FDA in which the company was guided to expand its intended use of NRX-101 from the original population of patients with acute suicidality, who might be treated in a hospital environment to the broader population of patients with subacute suicidal ideation, which we now describe as treatment-resistant bipolar depression. In other words, patients who are treated in the outpatient setting.

該試驗的結果有可能用於註冊備案。僅針對該公司2023年1月與FDA舉行的會議，會議指導該公司將NRX-101的預期用途從最初可能在醫院環境中接受治療的急性自殺患者人群擴大到更廣泛的人群具有亞急性自殺意念的患者，我們現在將其描述為難治性雙相憂鬱症。換句話說，就是在門診接受治療的患者。

Based on the guidance of the FDA and the company's completion of manufacturing from Phase 3 commercial stage investigational products, we upgraded the ongoing clinical trial to a Phase 2b/3 trial early this year. In our last call, I shared with you the steps that we've taken to set a new standard for reliability on the MADRS, that is the Montgomery-Åsberg Depression Rating Scale measurements in trials such as this. The MADRS scale is our primary endpoint in this study and in virtually all industry depression studies.

根據 FDA 的指導以及公司已完成 3 期商業階段研究產品的生產，我們於今年年初將正在進行的臨床試驗升級為 2b/3 期試驗。在我們上次的電話會議中，我與大家分享了我們為 MADRS 可靠性制定新標準所採取的步驟，即在此類試驗中進行的蒙哥馬利-安斯伯格抑鬱量表測量。 MADRS 量表是我們在本研究以及幾乎所有產業蕭條研究中的主要終點。

The industry has previously accepted a six-point disparity between psychometric graders at study sites and master raters who checks those evaluations. Moreover, the industry has often settled for comparing only the baseline ratings between site raters and master raters.

該行業先前已經接受了研究中心的心理測量評分者與檢查這些評估的主評分者之間存在六分的差異。此外，業界通常只比較網站評估者和主評估者之間的基準評級。

Over the past year, several clinical trials of promising investigational medicine for depression have failed. So we decided to set a far more rigorous standard. First, we set our standards for agreements between the sites and the master raters at 3 points of difference on a 60-point rating scale rather than 6 points of difference. Second, we decided to require 90% agreement between sites and master raters in order to keep the site and the program. Third, we decided to check the agreement on every patient rating, not just the baseline rating.

在過去的一年裡，一些有希望的憂鬱症研究藥物的臨床試驗都失敗了。因此我們決定制定一個更嚴格的標準。首先，我們將網站和主評分者之間的協議標準設定為 60 分評分量表上的 3 分差異，而不是 6 分差異。其次，我們決定要求網站和主評估者之間達成 90% 的協議，以保留網站和項目。第三，我們決定檢查每個患者評分的一致性，而不僅僅是基線評分。

As of today, I'm pleased to tell you that our clinical team has maintained 95% agreement between study sites and master raters. That doesn't mean that our drug will work. It still has to be the standard of care. It does mean, however, that we have markedly increased the chance of determining a difference between the drug group and the standard of care group.

截至今天，我很高興地告訴您，我們的臨床團隊在研究中心和主要評估者之間保持了 95% 的一致性。這並不意味著我們的藥物會起作用。它仍然必須是護理標準。然而，這確實意味著我們顯著增加了確定藥物組和標準護理組之間差異的機會。

In our last call, I shared with you the steps that we took to implement a nationwide recruiting strategy with 1nHealth. That investment paid off with a substantial acceleration in our enrollment rate over the past quarter, a capability that will serve us well should the drug demonstrated efficacy in this upcoming readout.

在上次電話會議中，我與您分享了我們與 1nHealth 實施全國性招募策略所採取的步驟。這項投資得到了回報，上個季度我們的入組率大幅提高，如果該藥物在即將到來的讀數中顯示出療效，這種能力將為我們帶來很大幫助。

Also on that last call, I described the advances we made in manufacture of NRX-101, resulting in more than 1 million commercial-grade capsules in our warehouse. Product stability work has continued to support the targeted two-year plus shelf life at potential drug launch. In other words, at such time as this drug is approved, we intend to be immediately ready to ship it to patients.

同樣在最後一次電話會議上，我描述了我們在 NRX-101 製造方面的進步，使我們的倉庫中擁有超過 100 萬個商業級膠囊。產品穩定性工作繼續支持潛在藥物上市時兩年以上的目標保質期。換句話說，一旦這種藥物獲得批准，我們打算立即準備好將其運送給患者。

As you know, last June, we entered into an exclusive global development supply marketing and license agreement with Alvogen, Inc., and affiliated companies. Alvogen will pay NRX a $10 million milestone upon delivery of positive Phase 2b/3 results and the FDA's concurrence followed by $330 million of additional milestones and royalties of up to 15%. Further, Alvogen assumes essentially all development and commercialization costs associated with this indication from that point forward. The company solidified its working relationship with Alvogen over the last quarter. We've begun working in unison to plan the final development and commercialization of NRX-101.

如您所知，去年 6 月，我們與 Alvogen, Inc. 及其附屬公司簽訂了獨家全球開發供應行銷和授權協議。在獲得 2b/3 期積極結果並獲得 FDA 同意後，Alvogen 將向 NRX 支付 1000 萬美元的里程碑付款，隨後將支付 3.3 億美元的額外里程碑付款和高達 15% 的特許權使用費。此外，從那時起，Alvogen 基本上承擔了與該適應症相關的所有開發和商業化成本。該公司在上個季度鞏固了與 Alvogen 的合作關係。我們已經開始齊心協力規劃 NRX-101 的最終開發和商業化。

Based on the milestones achieved during this quarter, the NRX-101 project is on track for completion of a pivotal trial in coordination with the commercial stage partner in less than two years from three initiation in March 2022.

根據本季取得的里程碑，NRX-101計畫預計將在與商業階段合作夥伴的協調下，自 2022 年 3 月啟動三項試驗以來，在不到兩年的時間內完成一項關鍵試驗。

So now, let's talk about NRX-101 for chronic pain. That's an indication that we only began talking to you about a quarter ago. The company has previously detailed the scientific basis for treatment of chronic pain with D-cycloserine as outlined in 2016 scientific paper published by Dr. Schnitzer and his colleagues and in the white paper that we've posted on our website and on the scientific servers.

現在，讓我們來談談 NRX-101 治療慢性疼痛的情況。這表明我們大約一個季度前才開始與您交談。該公司先前詳細介紹了用 D-環絲氨酸治療慢性疼痛的科學依據，如 Schnitzer 博士及其同事發表的 2016 年科學論文以及我們在我們的網站和科學伺服器上發布的白皮書中所述。

In the third quarter, we licensed the US patent for the use of D-cycloserine in treating chronic pain. And now, we filed an Investigational New Drug application [that] was accepted by the FDA to initiate commercial drug development of NRX-101 in chronic pain.

第三季度，我們獲得了使用 D-環絲胺酸治療慢性疼痛的美國專利。現在，我們提交了一項新藥研究申請，該申請已被 FDA 接受，以啟動 NRX-101 治療慢性疼痛的商業藥物開發。

As you know, chronic pain affects more than 15 million American adults compared to the approximately 3 million who report thoughts of suicide on an annual basis. There's been no new non-opioid class of drugs to treat no susceptive pain. That pain that's caused by stimulation of peripheral nerves, such as low back pain, knee pain, the most common pain that people talk about in the past two decades, and NRX-101 has the potential to be the first NMDA-antagonist drug to seek approval for this indication.

如你所知，慢性疼痛影響超過 1500 萬美國成年人，而每年約有 300 萬美國人有自殺念頭。目前還沒有新的非鴉片類藥物可以治療非敏感性疼痛。那些由周邊神經刺激引起的疼痛，例如腰痛、膝蓋痛，這是過去二十年來人們談論最多的疼痛，NRX-101有潛力成為第一個尋求的NMDA拮抗劑藥物批准該適應症。

Today, ketamine is used off-label to treat no susceptive pain despite its clear limitations, which we've described as the addiction, neurotoxicity, hallucination, and the need for IV administration. We now await results for 200 person randomized prospective trial funded by the US Department of Defense in which patients with chronic pain were randomly assigned to 400 milligrams a day of D-cycloserine versus placebo. The investigators have identified primary completion of these trials occurring this month.

如今，儘管氯胺酮有明顯的局限性，但它已被超適應證用於治療非敏感性疼痛，我們將其描述為成癮、神經毒性、幻覺和靜脈注射的需要。我們現在正在等待美國國防部資助的 200 人隨機前瞻性試驗的結果，其中慢性疼痛患者被隨機分配每天服用 400 毫克的 D-環絲氨酸與安慰劑。研究人員已確定這些試驗將於本月初步完成。

We've received a communication from the investors yesterday that the Investigational Review Board has cleared the study database for analysis, and the study statisticians are now beginning their final work. Should these trial results support efficacy of DCS in the treatment of chronic low back pain, the results are expected to provide a breakthrough therapy path toward treatment of chronic pain with D-cycloserine and DCS-containing medicines.

昨天我們收到了投資者的來信，表示研究審查委員會已清理研究資料庫以進行分析，研究統計學家現在正在開始他們的最後工作。如果這些試驗結果支持 DCS 治療慢性下背痛的功效，則預計該結果將為使用 D-環絲胺酸和含有 DCS 的藥物來治療慢性疼痛提供突破性的治療途徑。

Today, we're announcing that we've entered NRX-101 for consideration by the multibillion dollar National Institute of Health HEAL initiative, that's HEAL, and its national consortium of clinical trial sites known as EPPICNET. This initiative was funded by the US Congress to test innovative non-opioid pain medicines for chronic pain. We believe that NRX-101 represents the first NMDA-targeted non-addictive medicine to be offered to this program. Should the DoD-funded trial yielded encouraging data, we anticipate that nondilutive sources of capital will be available to us, given the national focus on the opioid crisis, progress in treating chronic pain with NRX-101. They open a far larger market for NRX-101 than anything we've talked about related to the psychiatry indications.

今天，我們宣布我們已將 NRX-101 納入 NRX-101 供耗資數十億美元的國家衛生研究院 HEAL 計劃（即 HEAL）及其國家臨床試驗站點聯盟（稱為 EPPICNET）考慮。該計劃由美國國會資助，旨在測試治療慢性疼痛的創新非鴉片類止痛藥。我們相信 NRX-101 代表了第一個針對該計畫的 NMDA 標靶非成癮藥物。如果國防部資助的試驗產生令人鼓舞的數據，鑑於國家對阿片類藥物危機的關注以及 NRX-101 治療慢性疼痛的進展，我們預計我們將獲得非稀釋性資本來源。它們為 NRX-101 開闢了一個比我們所討論的任何與精神病學適應症相關的市場都要大得多的市場。

Now, let's discuss our other NMDA-target therapy, NRX-100, which is a proprietary presentation of IV ketamine for suicidal depression. Prior to this past quarter, we didn't prioritize this initiative because frankly, we expected intranasal racemic ketamine to demonstrate efficacy in reducing suicidality in depressed patients. Unfortunately, the intranasal drug failed two months ago in clinical trials in patients for suicidal ideation. That's a drug that's obviously not connected to our company.

現在，我們來討論我們的另一種 NMDA 標靶療法 NRX-100，它是靜脈注射氯胺酮治療自殺性憂鬱症的專有產品。在上個季度之前，我們沒有優先考慮這項舉措，因為坦白說，我們預計鼻內外消旋氯胺酮能夠有效降低憂鬱症患者的自殺率。不幸的是，兩個月前，這種鼻內藥物在自殺意念患者的臨床試驗中失敗了。那是一種顯然與我們公司無關的藥物。

Intranasal ketamine previously failed for the treatment of chronic pain in 2006. So in our view, the manner in which ketamine is absorbed through the nose may be fundamentally different from its effect as an IV drug. When we met with FDA in January 2023, the agency strongly encouraged us to develop ketamine as a label drug rather than rely on prior stabilization suicidality and depression that's achieved through the common clinical practice -- through today's clinical practice of infusing generic ketamine that's compounded in licensed pharmacies.

鼻內氯胺酮先前在2006年治療慢性疼痛時失敗了。因此我們認為，氯胺酮透過鼻子吸收的方式可能與其作為靜脈注射藥物的效果有根本不同。當我們在2023 年1 月與FDA 會面時，該機構強烈鼓勵我們開發氯胺酮作為標籤藥物，而不是依賴於透過常見的臨床實踐（透過今天的輸注通用氯胺酮的臨床實踐）來穩定自殺傾向和憂鬱症。持牌藥局。

Shortly thereafter, the FDA issued the first of two advisory letters warning against the practice of compounding of ketamine, and FDA began a program of rigorous inspections of compounding pharmacies, significantly upgrading the standards that FDA requires and forcing some pharmacies to close. The challenge we faced in responding to FDA's guidance is that a definitive trial of IV ketamine in large numbers of patients with acute suicidality is far more complex and expensive than could be achieved by small companies such as ours. Moreover, it would take an additional two to three years. Indeed, no US entity has performed a large clinical trial or a multicenter clinical trial of ketamine in suicidal patients.

此後不久，FDA 發布了兩封警告信中的第一封，警告人們不要配製氯胺酮，並且FDA 開始了一項對配製藥房進行嚴格檢查的計劃，顯著提高了FDA 要求的標準，並迫使一些藥房關閉。我們在響應 FDA 指導時面臨的挑戰是，在大量急性自殺患者中進行靜脈注射氯胺酮的最終試驗比我們這樣的小公司所能實現的要復雜和昂貴得多。而且，還需要兩三年的時間。事實上，美國還沒有實體對自殺患者進行大型臨床試驗或多中心氯胺酮臨床試驗。

Fortunately, however, the government of France did invest in such a trial starting in 2015. A trial conducted in seven French psychiatric hospitals among 156 patients with acute suicidality. So based on the FDA's advice on ketamine, we established a scientific collaboration with Professor Marion Leboyer of Inserm, one of France's leading universities; and Professor Mocrane Abbar of Lyon, France, under which we gained government support to obtain the patient-level results from their groundbreaking trial and to submit those results to FDA in support of a new drug approval for intravenous ketamine.

不過幸運的是，法國政府確實從 2015 年開始投資了這樣的一項試驗。一項試驗在法國七家精神病院進行，受試者為 156 名患有急性自殺傾向的患者。因此，根據 FDA 對氯胺酮的建議，我們與法國頂尖大學之一 Inserm 的 Marion Leboyer 教授建立了科學合作；和法國里昂的Mocrane Abbar 教授，在該計畫下，我們獲得了政府的支持，從他們的開創性試驗中獲得了患者水平的結果，並將這些結果提交給FDA，以支持靜脈注射氯胺酮新藥的批准。

As you have seen in our presentations, the findings of the trial demonstrated overwhelmingly positive statistically significant reduction in both suicidality, the primary endpoint of the trial, and depression, the secondary endpoint among patients treated with intravenous ketamine compared to those treated with placebo. The patient-level deidentified data from France have now been received by our team of statisticians and are being assembled in the electronic format required for submission to the FDA.

正如您在我們的演示中所看到的，該試驗的結果表明，與接受安慰劑治療的患者相比，靜脈注射氯胺酮治療的患者自殺率（試驗的主要終點）和抑鬱症（次要終點）均顯著降低，具有統計意義。我們的統計學家團隊現已收到來自法國的患者級去識別化數據，並正在以提交給 FDA 所需的電子格式進行組裝。

Today, I'm pleased to share that the company is now negotiating access and has a preliminary agreement on confirmatory patient-level data from a US-based trial performed at a leading university and funded by the National Institutes of Health. Having taken advice from our regulatory legal consultants, we believe that these two multicenter randomized prospective trials that encompass more than 240 participants combined with randomized prospective data on more than 200 US patients when submitted for review provide evidence of safety and efficacy of intravenous ketamine in reducing both suicidality and depression among suicidal patients. We expect to transmit those data to FDA by the end of the quarter.

今天，我很高興地告訴大家，該公司正在就訪問進行談判，並就來自美國一所領先大學進行的、由美國國立衛生研究院資助的一項試驗的驗證性患者級數據達成了初步協議。在聽取了我們的監管法律顧問的建議後，我們相信，這兩項多中心隨機前瞻性試驗涵蓋了240 多名參與者，結合提交審查時涉及200 多名美國患者的隨機前瞻性數據，提供了靜脈注射氯胺酮在降低風險方面的安全性和有效性的證據。自殺患者的自殺傾向和憂鬱症。我們預計在本季末將這些數據傳輸給 FDA。

Although the biotech industry rightly focuses on safety and efficacy is key to securing drug approval, submission of an NDA for the use of IV ketamine is also dependent on documenting the manufacture and packaging of a new drug presentation in a long-term shelf, stable manner with control of impurities and other hallmarks of good manufacturing practices.

儘管生物技術行業正確地關注安全性和有效性是獲得藥物批准的關鍵，但提交靜脈注射氯胺酮使用的新藥申請還取決於以長期、穩定的方式記錄新藥的生產和包裝控制雜質和良好生產規範的其他標誌。

Indeed, Phase 3 biotechnology products are often delayed by unexpected manufacturing failures, perhaps more often, than by unexpected clinical trial results. That's why we're excited to announce the signing of a development and manufacturing agreement with Nephron Pharmaceuticals, Inc., to develop a single patient presentation of ketamine that's expected to overcome some of the formulation deficiencies of existing forms of ketamine that were originally developed for anesthesia and is expected to have diversion-resistant and tamper-resistant features.

事實上，第三階段生物技術產品常常因意外的製造失敗而被推遲，或許比意外的臨床試驗結果更常見。這就是為什麼我們很高興地宣布與 Nephron Pharmaceuticals, Inc. 簽署開發和製造協議，開發一種氯胺酮單一患者演示，有望克服現有氯胺酮形式的一些配方缺陷，這些形式最初是為麻醉，預計具有防轉移和防篡改功能。

We believe this latter aspect is important because of the well-known uses of ketamine has a drug of abuse and also as a vehicle for daybreak. We've worked with Nephron and its [visionary] founder and owner, Lou Kennedy, on previous projects and have great confidence in the Nephron team. In this case, Nephron is particularly suited as a partner because of their enormous investment in sterile blow-fill-seal technology that's ideally suited to our planned commercial presentation.

我們認為後一個方面很重要，因為氯胺酮的眾所周知的用途是一種濫用藥物，也是黎明的工具。我們曾與 Nephron 及其[富有遠見的]創始人兼所有者 Lou Kennedy 在先前的專案中合作過，並對 Nephron 團隊充滿信心。在這種情況下，Nephron 特別適合作為合作夥伴，因為他們在無菌吹灌封技術方面進行了大量投資，該技術非常適合我們計劃的商業演示。

Our current timeline project submission of a new drug application for ketamine in the first quarter of 2024 with a targeted to-do for date in the fourth quarter of 2024. Now, we don't anticipate funding the ketamine initiative with core and NRX assets and our guidance in today's queue advises investors of our plan to establish a ketamine-focused spin-off company that will potentially provide current and new investors with both capital appreciation and a royalty stream.

我們目前的時間表項目是在 2024 年第一季提交氯胺酮新藥申請，目標是在 2024 年第四季度完成。現在，我們預計不會利用核心資產和 NRX 資產為氯胺酮計劃提供資金，我們今天隊列中的指南向投資者建議我們計劃建立一家專注於氯胺酮的分拆公司，該公司將有可能為現有和新投資者提供資本增值和特許權使用費。

Last week, we received a term sheet for up to $30 million in anchor financing for this new business entity. In this plan, a portion of the equity to be built in the ketamine asset will be allocated to existing shareholders as of record date to be established potentially with an ongoing royalty stream to NRX, to those shareholders, and to the new investors. This structure will be discussed at the upcoming annual meeting of shareholders, which will hope all of you will attend.

上週，我們收到了一份為這個新業務實體提供高達 3,000 萬美元錨定融資的條款清單。在該計劃中，氯胺酮資產中的部分股權將分配給截至登記日的現有股東，可能會向 NRX、這些股東和新投資者持續收取特許權使用費。這個架構將在即將召開的股東年會上討論，希望大家都能參加。

Facing acute public health need for safely manufactured diversion and abuse-resistant form of ketamine, particularly in light of drug shortages caused by newly and appropriately rigorous FDA manufacturing standards. NRX anticipates pursuing a near-term potential solution to address this public health need by the end of 2024.

公共衛生部門迫切需要安全生產氯胺酮的轉移和抗濫用形式，特別是考慮到新的、適當嚴格的 FDA 生產標準導致藥物短缺。 NRX 預計在 2024 年底尋求近期潛在解決方案來滿足這項公共衛生需求。

Finally, we expect that our focus on urinary tract infection is a bit surprising, given our identity as a CNS-focused company. Although treatment of UTI is quite different from the use of NRX-101 to treat central nervous system disorders, D-cycloserine was originally developed as an antibiotic because of its role in disrupting the cell wall of certain bacteria. Now, surprising as that may sound, that's true of a number of drugs used in psychiatry today. They all began as antibiotics.

最後，考慮到我們作為一家專注於中樞神經系統的公司的身份，我們預計我們對泌尿道感染的關注有點令人驚訝。儘管泌尿道感染的治療與使用 NRX-101 治療中樞神經系統疾病有很大不同，但 D-環絲氨酸最初是作為抗生素開發的，因為它具有破壞某些細菌細胞壁的作用。現在，儘管這聽起來可能令人驚訝，但當今精神病學中使用的許多藥物都是如此。它們都是從抗生素開始的。

D-cycloserine fell out of favor as an antibiotic in the 1970s because of the CNS effects caused by NMDA-blocking properties. And because of the widespread availability of effective first- and second-generation antibiotics. However, DCS is unique as an antibiotic, and that is nearly 100% excreted on metabolized in the urine. And therefore, it achieves high urinary tract levels with oral administration.

由於 NMDA 阻斷特性引起中樞神經系統影響，D-環絲氨酸在 20 世紀 70 年代作為抗生素不再受歡迎。而且由於有效的第一代和第二代抗生素的廣泛使用。然而，DCS 作為一種抗生素是獨特的，幾乎 100% 會透過尿液代謝排出體外。因此，口服給藥可達到較高的尿道水平。

As you probably know, many of the newer third- and fourth-generation antibiotics require intravenous administration to treat complicated UTI. Our clinical experience in psychiatry suggests that the lurasidone component of NRX-101 blocks unwanted CNS side effects and unlocks the potential of D-cycloserine to treat antibiotic-resistant urinary tract infection with a decreased propensity to cause unwanted CNS effects.

您可能知道，許多較新的第三代和第四代抗生素需要靜脈注射來治療複雜的泌尿道感染。我們在精神病學方面的臨床經驗表明，NRX-101 的魯拉西酮成分可以阻止不必要的CNS 副作用，並釋放D-環絲氨酸治療抗生素抗藥性尿路感染的潛力，同時降低引起不必要的CNS 影響的可能性。

In recent years, increased antibiotic resistance to common pathogens that cause urinary tract infections and urosepsis. In other words, sepsis that originates in the urinary tract has resulted in a market increase in complicated urinary tract infection hospitalization and death from urosepsis.

近年來，對引起泌尿道感染和尿膿毒症的常見病原體的抗生素抗藥性增加。換句話說，起源於泌尿道的敗血症導致複雜性泌尿道感染住院和尿膿毒症死亡的市場增加。

Probably everyone on this call knows someone who's developed a UTI and ended up receiving IV antibiotics in the hospital or at home. The US Center for Disease Control and Prevention reports that more than 1.7 million Americans contract sepsis each year, of whom at least 350,000 die during their hospitalization or discharge to hospice. In 2015, DCS was demonstrated to be effective against pathogens that are increasingly likely to cause sepsis and increasingly resistant to first- and second-line antibiotics.

也許這次通話中的每個人都認識患有泌尿道感染並最終在醫院或家中接受靜脈注射抗生素的人。美國疾病管制與預防中心報告稱，每年有超過 170 萬美國人感染敗血症，其中至少 35 萬人在住院或出院到臨終關懷中心期間死亡。 2015年，DCS被證明可以有效對抗越來越有可能引起敗血症並且對第一線和第二線抗生素抗藥性越來越強的病原體。

So in Q3, we tested NRX-101 and its components against resistant pathogens that appear on the congressionally mandated qualified infectious disease product list. And we proved in vitro effectiveness that is effectiveness in the laboratory against antibiotic-resistant E. coli, Pseudomonas, and Acinetobacter. These are bugs that kill patients every day, and in vitro effectiveness is what's required to meet the requirements of the QIDP program.

因此，在第三季度，我們測試了 NRX-101 及其成分針對國會授權的合格傳染病產品清單中出現的抗藥性病原體的情況。我們在體外證明了其有效性，即在實驗室中對抗抗生素抗藥性大腸桿菌、假單胞菌和不動桿菌的有效性。這些細菌每天都會導致患者死亡，而體外有效性是滿足 QIDP 計劃要求的必要條件。

Qualification for QIDP affords a sponsor five years of additional market exclusivity from FDA regardless of whether or not you have a patent on the drug. And we do have a composition of patent on NRX-101. Together with Fast Track Designation and priority review, we believe that NRX-101 as an oral medicine has the potential to demonstrate benefit in patients who would otherwise require intravenous third- and fourth-generation antibiotics. We believe there are approximately 3 million such patients a year for contract with complicated UTI.

QIDP 資格為申辦者提供 FDA 五年的額外市場獨佔權，無論您是否擁有該藥物的專利。我們確實擁有NRX-101的專利組合物。結合快速通道指定和優先審查，我們相信 NRX-101 作為口服藥物有可能為那些需要靜脈注射第三代和第四代抗生素的患者帶來益處。我們相信每年約有 300 萬此類患者患有複雜性泌尿道感染。

Should NRX-101 succeed in clinical trials, the company has a planned follow-on product that's anticipated to achieve another 20 years of patent exclusivity. Based on the in vitro study that we've performed, we now have submitted an Investigational New Drug application, requesting QIDP status, Fast Track Designation, and priority review from the FDA. We're expecting the FDA to approve this IND by the end of this year, by the end of 2023.

如果 NRX-101 在臨床試驗中取得成功，該公司計劃推出後續產品，預計將獲得另外 20 年的專利獨佔權。根據我們進行的體外研究，我們現在已提交研究性新藥申請，請求 QIDP 狀態、快速通道指定以及 FDA 的優先審查。我們預計 FDA 將在今年底（2023 年底）之前批准該 IND。

As with the ketamine development project, we don't anticipate funding this initiative with core NRX assets, and we're exploring structures for a new entity that would provide current and new investors with both capital appreciation and a royalty stream. However, the cost of bringing NRX-101 to market as an antibiotic is far lower than one might imagine. Because we've already manufactured the drug, we already have the necessary preclinical safety, toxicity, pharmacokinetics, pharmacodynamics data in our hands from our bipolar program.

與氯胺酮開發項目一樣，我們預計不會使用 NRX 核心資產為該計劃提供資金，並且我們正在探索新實體的結構，該實體將為現有和新投資者提供資本增值和特許權使用費。然而，將 NRX-101 作為抗生素推向市場的成本遠低於人們的想像。因為我們已經生產了該藥物，所以我們已經從雙極計劃中獲得了必要的臨床前安全性、毒性、藥物動力學、藥效學數據。

We've already begun conversations with investor groups who recognize the extraordinary public health need. Should the company succeed in serving 10% of the cUTI market. We believe the revenue from NRX-101 for this indication as the potential to reach hundreds of millions of dollars annually based on 3 million cases per year in the US.

我們已經開始與認識到特殊公共衛生需求的投資者團體進行對話。公司是否能夠成功服務 10% 的 cUTI 市場。我們相信，基於美國每年 300 萬例，NRX-101 針對該適應症的收入每年有可能達到數億美元。

Finally, I'd like to address a challenging issue that's frequently raised with us by investors. Investors have contacted us with the belief that the company's share price may be adversely affected by short sales of stock that may frequently accompany positive news. While covered short sales such as those sales better associated with borrowing in existing share of stock are legal, naked shorting, without an underlying borrowed share, is clearly illegal.

最後，我想談談投資人經常向我們提出的一個具有挑戰性的問題。投資人與我們聯繫，認為該公司的股價可能會受到經常伴隨利好消息的股票賣空的不利影響。雖然有擔保賣空（例如與現有股票借入更相關的銷售）是合法的，但沒有基礎借入股票的裸賣空顯然是非法的。

Importantly, a recent federal court decision holds brokerages liable for damages to companies associated with persistent naked short positions. Based on these queries from investors, in Q3, we contracted with ShareIntel, Inc., to examine disparities between NRX stock positions as reported by brokerages and NRX shares reported by DTC, the electronic clearinghouse for the Nasdaq exchange.

重要的是，聯邦法院最近的一項裁決要求經紀公司對與持續裸空頭寸相關的公司造成的損失承擔責任。根據投資者的這些詢問，我們在第三季度與 ShareIntel, Inc. 簽訂了合同，檢查經紀公司報告的 NRX 股票頭寸與納斯達克交易所電子清算所 DTC 報告的 NRX 股票頭寸之間的差異。

Today, we're announcing that persistent disparities of approximately 1 million to 1.5 million shares were identified. In other words, those may be naked short positions. The company has now instructed this counsel to initiate outreach to compliance departments of the identified -- identifying that all uncovered short positions in the company stock be closed via a forced delivery of shares. The company has been advised by counsel that this action has resulted in positive share action in the past when implemented by other issuers of Nasdaq stock.

今天，我們宣布發現了大約 100 萬至 150 萬股的持續差異。換句話說，這些可能是裸空頭部位。該公司現已指示該律師開始與已確定的合規部門進行聯繫，確定該公司股票中所有未覆蓋的空頭部位都將透過強制交付股票來平倉。該公司律師告知，納斯達克股票的其他發行人過去實施這項行動時，已導致積極的股票行動。

Now, I'm going to ask Rich Narido, our Chief Financial Officer, to review the third-quarter financials. Rich?

現在，我將請我們的財務長 Rich Narido 審查第三季的財務狀況。富有的？

Thank you Jonathan, and good afternoon, everyone. I will now review the highlights of our third-quarter 2023 financial results. Before reviewing the numbers, it's important to recognize that we have consistently reduced our cash expenditures and expect to further reduce those expenditures as we complete the NRX-101 clinical trial.

謝謝喬納森，大家下午好。我現在將回顧我們 2023 年第三季財務表現的要點。在查看這些數字之前，重要的是要認識到我們一直在減少現金支出，並預計在完成 NRX-101 臨床試驗後進一步減少這些支出。

In August, the company entered into a securities purchase agreement, pursuant to which the company issued 3 million shares of the company's Series A convertible preferred stock and one investor warrant for every share of Series A preferred stock issue. The aggregate proceeds of the company from the private placement was approximately $1.2 million before expense. The company intends to use the net proceeds from such offering for working capital and general corporate purposes.

8月，公司簽訂了證券購買協議，根據該協議，公司發行300萬股A系列可轉換優先股，每發行一股A系列優先股發行一份投資者認股權證。該公司私募配售的總收益約為 120 萬美元（未計費用）。該公司打算將此次發行的淨收益用於營運資金和一般公司用途。

For the three months ended September 30, 2023, and NRX Pharmaceuticals recorded $3.3 million of research and development expenses compared to $4.1 million for the three months ended September 30, 2022. The decrease is related primarily to clinical development expenses and fees paid to regulatory and product development before.

截至2023 年9 月30 日止三個月，NRX Pharmaceuticals 的研發費用為330 萬美元，而截至2022 年9 月30 日止三個月為410 萬美元。這項減少主要與臨床開發費用以及支付給監管機構和機構的費用有關。先前的產品開發。

For the same three-month period, we recorded a 50% reduction in general and administrative expenses from $5 million in the third quarter of 2022 to $2.5 million for the three months ended September 30, 2023. The decrease of $2.5 million is related primarily to decreases in employee-related expenses, legal, insurance, and accounting costs. The nine-month period from January to September 2023 similarly shows decreased expenditures as reflected in our financial statements compared to the prior year.

在同一三個月期間，我們的一般和管理費用減少了50%，從2022 年第三季的500 萬美元減少到截至2023 年9 月30 日的三個月的250 萬美元。減少250 萬美元主要與與員工相關的費用、法律、保險和會計費用減少。正如我們的財務報表所反映的，與前一年相比，2023 年 1 月至 9 月的九個月期間支出也有所減少。

As of September 30, 2023, we had $8.9 million in cash and cash equivalents. These working capital assets are expected to fund the company's operations through the expected achievement of the four key milestones discussed today. Additionally, we are evaluating operational efficiencies associated with the completion of manufacturing activities to extend this runway.

截至 2023 年 9 月 30 日，我們擁有 890 萬美元的現金和現金等價物。這些營運資本資產預計將為公司的營運提供資金，以實現今天討論的四個關鍵里程碑的預期成果。此外，我們正在評估與完成製造活動相關的營運效率，以擴展這條跑道。

With that, I will turn it back to Steve for closing remarks. Steve?

至此，我將把它轉回給史蒂夫做總結發言。史蒂夫？

Thanks, Rich. In the next several months, we expect to see multiple efforts at NRX come to fruition, which we believe may provide significant upside to our investors. We are near completion of enrollment in our suicidal bipolar depression trial with NRX-101 and are moving toward data early next year. We await data from Northwestern University's Department of Defense-funded trial in chronic pain. We expect to receive a response from FDA on our Qualified Infectious Disease Product request for NRX-101 in urinary tract infection, and we expect to position NRX-101 in a new entity to file an NDA for IV ketamine in suicidal depression in the first part of next year.

謝謝，里奇。在接下來的幾個月中，我們預計 NRX 的多項努力將取得成果，我們相信這可能會為我們的投資者帶來巨大的好處。我們即將完成 NRX-101 自殺性雙極性憂鬱症試驗的入組工作，並將於明年初獲取數據。我們正在等待西北大學國防部資助的慢性疼痛試驗的數據。我們期望收到FDA 對NRX-101 治療尿路感染的合格傳染病產品請求的回應，並且我們期望將NRX-101 定位在一個新實體中，以便在第一部分提交IV 氯胺酮治療自殺抑鬱症的新藥申請(NDA)明年的。

Investors have expressed some concern about whether we will maintain compliance with Nasdaq listing requirements. We are working closely with Nasdaq staff and outside consultants in that regard. As we said in our 8-K filing, achieving any of the four milestones identified above has the potential to lift our stock price range required by Nasdaq. As those milestones play out, we will continue to act in a manner that is most supportive of our shareholders.

投資者對我們是否會繼續遵守納斯達克上市要求表示一些擔憂。在這方面，我們正在與納斯達克工作人員和外部顧問密切合作。正如我們在 8-K 文件中所說，實現上述四個里程碑中的任何一個都有可能提高納斯達克要求的股價範圍。隨著這些里程碑的實現，我們將繼續以最支持股東的方式行事。

For a small biotechnology company, we have tremendous amount of opportunity to rebuild shareholder value arriving in the near term. I'm incredibly proud of our team, our collaborators and partners, and most of all, the patients who have made such an important contribution to these efforts. Together, we are pursuing NRX's goal of bringing hope to life on a daily basis.

對於一家小型生技公司來說，我們有大量機會在短期內重建股東價值。我為我們的團隊、我們的合作者和合作夥伴，最重要的是為這些努力做出如此重要貢獻的患者感到無比自豪。我們共同追求 NRX 的目標，即為日常生活帶來希望。

Operator, we are ready to take questions.

接線員，我們準備好回答問題。

(Operator Instructions) Ed Woo, Ascendiant Capital.

（操作員指令）Ed Woo，Ascendiant Capital。

Yeah. Thank you for taking my question. My question is, as you guys start pursuing new opportunities with chronic pain and infectious disease, does this affect your partnership with Lotus or Alvogen? And do they have any opportunities to have first rights to get involved with this -- with you?

是的。感謝您回答我的問題。我的問題是，當你們開始尋求治療慢性疼痛和傳染病的新機會時，這是否會影響你們與 Lotus 或 Alvogen 的合作關係？他們是否有機會擁有優先權來參與這件事——和你一起？

There is a right of -- thank you. There is a right of first negotiation, but not a right of first refusal.

有權利——謝謝。有優先談判權，但沒有優先拒絕權。

Great. And what kind of a negotiation process and when do they have to make a decision process? Or is this something that's going to be ongoing with your clinical trials?

偉大的。他們需要什麼樣的談判過程以及何時做出決策？或者這是您的臨床試驗中正在進行的事情嗎？

I believe it will be ongoing, but I believe that they have 10 days from when we make a proposal to give us a decision. And then they're free to partner the product right in ways that are no less favorable to NRX.

我相信這將會持續下去，但我相信從我們提出提案後他們有 10 天的時間做出決定。然後他們就可以自由地以同樣有利於 NRX 的方式來合作產品。

Great. Thank you for providing the question -- answers to my question. Thank you, and I wish you guys good luck.

偉大的。感謝您提出問題—回答我的問題。謝謝你們，祝你們好運。

Ashia, this is Matt Duffy. And I have received some electronic questions for management here. The first one, I think would go to Steven? It looks like it dovetails off that last one which is, how is the partnership with Alvogen going so far in general?

阿希亞，這是馬特·達菲。我在這裡收到了一些針對管理層的電子問題。第一個，我想會是史蒂文？看起來它與最後一個問題相吻合，即到目前為止與 Alvogen 的合作進展如何？

I think it's going really well. I mean, I have a good working relationship with the CEO of Alvogen. We've established a number of committees. We meet regularly, and it seems like we're generally forging alignment on our goals for development and commercialization of the project.

我認為一切進展順利。我的意思是，我與 Alvogen 執行長有著良好的工作關係。我們成立了多個委員會。我們定期會面，似乎我們總體上正在就專案的開發和商業化目標達成一致。

Great. Another question came in, I think for Dr. Javitt. Can you tell us more about your plans for the ketamine spin-off? These assets, potential funding benefit to our shareholders?

偉大的。另一個問題出現了，我想是針對賈維特醫生的。您能告訴我們更多有關氯胺酮分拆計畫的資訊嗎？這些資產，潛在的資金效益對我們的股東有什麼好處？

Well, I think it's important to start out by understanding the challenge that we have where on one hand, we've been working for many years to develop NRX-101. It's a core asset, a drugs that could readily be worth multiple billions of dollars if it succeeds in clinical trials as compared to the projects in ketamine and complicated UTI. While they're enormously attractive and they're nearer term in terms of their opportunity, ultimately, their smaller revenue opportunities, but very meaningful revenue opportunities.

嗯，我認為首先了解我們所面臨的挑戰很重要，一方面，我們多年來一直致力於開發 NRX-101。這是一項核心資產，與氯胺酮和複雜尿路感染計畫相比，如果它在臨床試驗中取得成功，這種藥物的價值可能會達到數十億美元。雖然它們具有巨大的吸引力，而且就機會而言，它們的期限也比較近，但最終，它們的收入機會較小，但卻是非常有意義的收入機會。

Now, imagine, for example, if ketamine generated $100 million a year of profit, you're talking about a company like ours at its current cap table. That's more than a dollar a share. So they are enormously attractive opportunities for shareholders and at the same time, creating dilution within the core company wouldn't make all that much sense for shareholders. And that's why, in our view, the most attractive opportunity for our current shareholders is to create these spin-offs, where we've already seen appetite from new investors to come in, help fund the spin-offs, but do it in a way that current investors will benefit in proportion to their current shareholder. Now, we can't talk too much about the details because that's something that's going to be part of our upcoming annual meeting and deliberation with our shareholders. But that's the general reason for thinking about the spin-off structure.

現在，想像一下，如果氯胺酮每年產生 1 億美元的利潤，那麼您談論的是像我們這樣的公司，目前的上限表。這比每股一美元還要多。因此，它們對股東來說是極具吸引力的機會，同時，在核心公司內部造成稀釋對股東來說沒有太大意義。這就是為什麼，在我們看來，對我們現有股東來說最有吸引力的機會是創建這些分拆，我們已經看到新投資者有興趣加入，幫助為分拆提供資金，但要以一種適當的方式進行。現有投資者將按照其現有股東的比例受益。現在，我們不能過多談論細節，因為這將成為我們即將舉行的年度會議和與股東審議的一部分。但這是考慮分拆結構的一般原因。

Okay. Sticking with the IV ketamine, one other question is it's for a clinical one for you, I think Dr. Javitt. Is IV ketamine really that much better than inhaled?

好的。堅持靜脈注射氯胺酮，另一個問題是它適合您的臨床用途，我認為賈維特博士。靜脈注射氯胺酮真的比吸入好嗎？

Well, we know from extensive literature and now from two well-controlled randomized prospective trials that IV ketamine works against acute suicidality. And in health ketamine has never demonstrated that in a large multicenter trial. What's important to recognize is that when you give ketamine IV, you know exactly what your blood levels are at every moment of the infusion.

嗯，我們從大量文獻和現在的兩項對照良好的隨機前瞻性試驗中得知，靜脈注射氯胺酮可以對抗急性自殺。在健康方面，氯胺酮從未在大型多中心試驗中證明過這一點。重要的是要認識到，當您靜脈注射氯胺酮時，您可以準確地知道輸注每個時刻的血液濃度。

When you put ketamine in the nose, you get an immediate spike of ketamine, followed by a tailing off, and you have a much less stable blood level. But more importantly, just because you put ketamine in the nose, you don't really know how it's going to get into the bloodstream of any individual patient. Some will go down the back of the throat, into the stomach can get absorbed. Some may go across the tissues of the nose directly into the bloodstream, and it's going to vary patient by patient. It's going to vary in terms of how the our nasal administration is carried out. And in fact, you wind up in a situation where you're creating a drug-device combination with a nasal sprayer that has to be regulated as a medical device.

當您將氯胺酮放入鼻子中時，氯胺酮會立即升高，然後逐漸下降，並且您的血液濃度會變得不穩定。但更重要的是，僅僅因為您將氯胺酮放入鼻子中，您並不真正知道它會如何進入任何患者的血液中。有些會順著喉嚨後面，進入胃裡才能被吸收。有些可能會穿過鼻子組織直接進入血液，具體情況因人而異。我們的鼻腔給藥方式會有所不同。事實上，您最終會遇到這樣的情況：您正在創建帶有鼻噴霧器的藥物設備組合，而該組合必須作為醫療設備進行監管。

So nasal ketamine has a history of disappointing industry. In 2006, there was a major failure associated with the US clinical trial for nasal ketamine and treatment of chronic pain. So from our perspective, IV ketamine is something that's ready for the market. It's being used widely off-label. It's essentially become a national standard of care. And we believe that an FDA-labeled tamper-resistant, diversion-resistant form of ketamine that's manufactured to current standards, not just the standards that were in place when ketamine was developed as an anesthetic, but manufactured to current standards is an important public health initiatives. And that's why we've chosen to embrace it.

因此鼻用氯胺酮有著令人失望的行業歷史。 2006年，美國鼻用氯胺酮治療慢性疼痛的臨床試驗發生重大失敗。因此，從我們的角度來看，靜脈注射氯胺酮已經為市場做好了準備。它被廣泛用於標籤外。它基本上已成為國家護理標準。我們相信，FDA 標記的防篡改、防轉移形式的氯胺酮，按照現行標準（不僅僅是開發氯胺酮作為麻醉劑時制定的標準）製造，而且按照現行標準製造，對公共健康至關重要倡議。這就是我們選擇擁抱它的原因。

Okay. Very good. Thanks. We have time for one more question, and here it is. With the Department of Defense study in pain is positive, what do you see as the clinical and regulatory pathway for NRX-101 in pain?

好的。非常好。謝謝。我們還有時間再問一個問題，就在這裡。鑑於國防部對疼痛的研究是積極的，您認為 NRX-101 治療疼痛的臨床和監管途徑是什麼？

Well, we've already filed an Investigational New Drug application with the FDA for the use of NRX-101 in pain and received an enthusiastic response, or response that we've seen this enthusiastic from the FDA Division of Anesthesia, Analgesia, and Addiction Products, which is the division that regulates pain products.

嗯，我們已經向 FDA 提交了一份使用 NRX-101 治療疼痛的研究性新藥申請，並收到了熱烈的回應，或者說我們已經從 FDA 麻醉、鎮痛和成癮部門看到了這種熱情的回應產品部門，負責監管疼痛產品。

Clearly, if the DoD trial is positive, that will be a critical piece of evidence. But additional randomized, controlled trials with NRX-101 in a commercial presentation would be required. We've talked about some of the nondilutive capital that's available not only through the NIH, but we would expect that the Department of Defense would want to continue development of this drug because there's such an acute need within DoD and elsewhere for a non-addictive, non-opioid pain medication. And certainly, a major initiative in chronic pain would require a capital raise from NRX's side, but we have ample belief that that capital would be available in the face of a positive readout in the 200-person trial.

顯然，如果國防部的試驗是積極的，那將是一個關鍵的證據。但還需要在商業演示中對 NRX-101 進行更多隨機對照試驗。我們已經討論了一些非稀釋性資本，這些資本不僅可以透過 NIH 獲得，而且我們預計國防部會希望繼續開發這種藥物，因為國防部和其他地方對非成癮性藥物的需求如此迫切，非阿片類止痛藥。當然，針對慢性疼痛的重大舉措需要 NRX 方面籌集資金，但我們有充分的理由相信，面對 200 人試驗的積極結果，這筆資金將可用。

Thanks. Thank you very much. Thank you, everyone. That's all the time we have for questions tonight. We appreciate you joining us. Let's talk about our journey, reaching these important milestones for the company over the coming months. And look forward to your participation in future calls.

謝謝。非常感謝。謝謝大家。今晚我們的提問時間就到此為止。我們感謝您加入我們。讓我們來談談我們的歷程，以及公司在未來幾個月內實現這些重要里程碑的歷程。並期待您參與未來的通話。

This concludes NRX Pharmaceuticals' third-quarter conference call. Thank you all for participating.

NRX Pharmaceuticals 第三季電話會議到此結束。感謝大家的參與。

This concludes today's conference call. You may disconnect your lines. Thank you for participating and have a pleasant day.

今天的電話會議到此結束。您可以斷開線路。感謝您的參與並祝您有個愉快的一天。