NRX Pharmaceuticals Inc (NRXP) 2023 Q2 法說會逐字稿

Good day and welcome to the NRX Pharmaceuticals Incorporated second-quarter 2023 earnings conference call. (Operator Instructions)

美好的一天，歡迎參加 NRX 製藥公司 2023 年第二季度收益電話會議。 （操作員說明）

Please note this event is being recorded.

請注意此事件正在被記錄。

I would now like to turn the conference over to Mr. Matthew Duffy, the company's Chief Business Officer. Please go ahead, sir.

現在我想將會議轉交給公司首席商務官 Matthew Duffy 先生。請繼續，先生。

Thank you, Joe. 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 experience or present expectations.

謝謝你，喬。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經驗或當前預期存在重大差異。

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. 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.

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信息包含在我們向 SEC 提交的定期報告中。本次電話會議期間做出的前瞻性陳述僅代表截至本新聞稿發布之日的情況，公司不承擔更新或修改前瞻性陳述的義務。

Information presented on this call is contained in the press release issued earlier today and the company's Form 10-Q filed today, which may be accessed from the Investor page of the NRX Pharmaceuticals, Inc. website.

本次電話會議中提供的信息包含在今天早些時候發布的新聞稿和公司今天提交的 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 the call are Stephen Willard, our Chief Executive Officer; Jonathan Javitt, our Chief Scientist; and Seth Van Voorhees, our Chief Financial Officer and Treasurer. Stephen and Jonathan will provide a summary of the company's progress. Seth 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.

與我一起參加電話會議的還有我們的首席執行官 Stephen Willard；喬納森·賈維特，我們的首席科學家；以及我們的首席財務官兼財務主管 Seth Van Voorhees。斯蒂芬和喬納森將總結公司的進展。塞思將審查公司的財務業績，然後斯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，我們將回答投資者的問題。

I'll now turn the call over to Stephen.

我現在將把電話轉給斯蒂芬。

Thank you, Matt. Good afternoon, everyone, and thank you for joining us. Our second quarter reflects an important inflection point for the company as we advance our novel NMDA platform. This expansion of our pipeline is driven by our signed partnership agreement with Alvogen and Lotus Pharmaceuticals related to the use of NRX-101, our breakthrough investigational medicine in bipolar depression with suicidality.

謝謝你，馬特。大家下午好，感謝您加入我們。隨著我們推進新穎的 NMDA 平台，第二季度反映了公司的一個重要轉折點。我們與 Alvogen 和 Lotus Pharmaceuticals 簽署的合作協議推動了我們產品線的擴張，該協議涉及 NRX-101 的使用，NRX-101 是我們治療伴有自殺傾向的雙相抑鬱症的突破性研究藥物。

The milestones and commitments within that partnership, as disclosed in our filings and described in the press release, provide the extensive financial resources needed to fund Phase 3 and commercialization of NRX-101 in this indication without additional dilution to our shareholders, should we deliver a statistically significant data readout.

正如我們在文件中披露的和新聞稿中所述，該合作夥伴關係中的里程碑和承諾提供了資助NRX-101 在該適應症中的第3 階段和商業化所需的廣泛財務資源，而無需對我們的股東進行額外稀釋，如果我們提供具有統計意義的數據讀出。

When we met with FDA last January, and FDA guided us to broaden our clinical indication and to develop a 1,500 person safety database, investors asked how we were going to fund this program. The Alvogen deal answers this question.

去年 1 月，當我們與 FDA 會面時，FDA 指導我們擴大臨床適應症並開發一個 1,500 人的安全數據庫，投資者詢問我們將如何為該項目提供資金。 Alvogen 交易回答了這個問題。

In our previous calls, we have explained the urgent unmet need for a medicine to treat this group of patients who have a 50% lifetime risk of suicide attempts and who have been excluded from trials of all previous antidepressants. The urgent need is detailed on our website and validated by FDA and an award of breakthrough therapy designation and a special protocol agreement.

在我們之前的電話會議中，我們解釋了對一種藥物的迫切需求未得到滿足，用於治療這組患者，這些患者終生有50% 的自殺未遂風險，並且已被排除在所有先前抗抑鬱藥的試驗之外。我們的網站詳細介紹了這一迫切需求，並經過 FDA 驗證，並授予突破性治療指定和特殊協議協議。

As further validation of the life-saving applications of this therapy, this week, we published the previously announced results of STABIL-B in the International Journal of Bipolar Disorders, a peer-reviewed, high-impact journal published by Springer Nature. The lead author is Professor Andrew Nierenberg who leads bipolar research at Mass General Hospital.

為了進一步驗證該療法的救生應用，本週，我們在 Springer Nature 出版的同行評審、高影響力期刊《國際雙相情感障礙雜誌》上發表了之前公佈的 STABIL-B 結果。主要作者是麻省總醫院領導雙相情感障礙研究的安德魯·尼倫伯格教授。

The article documents a nearly 8-point difference on the MADRS depression scale when NRX is tested against lurasidone, a difference approximately twofold greater than the difference seen when typical antidepressants are tested against placebo. Moreover, to our knowledge, this is the first oral drug to demonstrate a statistically significant reduction in suicidality, the benefits seen only previously with IV ketamine.

該文章記錄了當 NRX 與魯拉西酮進行測試時，MADRS 抑鬱量表上存在近 8 分的差異，這一差異大約是典型抗抑鬱藥與安慰劑進行測試時所見差異的兩倍。此外，據我們所知，這是第一種在統計上顯示出顯著降低自殺率的口服藥物，這種益處以前只有靜脈注射氯胺酮才能看到。

Now we are engaged in the Phase 2b/3 trial that seeks to document the benefits of NRX-101 in suicidal patients without prior IV ketamine. We have formed a joint steering committee with our partner. Our scientific and management teams are now working regularly in partnership with teams from Alvogen and Lotus in order to collaboratively bring a life-saving drug to market.

現在我們正在進行 2b/3 期試驗，旨在記錄 NRX-101 對未事先靜脈注射氯胺酮的自殺患者的益處。我們與合作夥伴成立了聯合指導委員會。我們的科學和管理團隊現在定期與 Alvogen 和 Lotus 的團隊合作，共同將救命藥物推向市場。

I am pleased to announce that our clinical trial is now within 20 patients, have an anticipated data readout. We are now establishing a broad base of study sites in anticipation of a substantially larger Phase 3 initiatives funded by our partners. And more importantly, we are seeing promising indications of quality, with 90% medication compliance and 94% concurrent of depression scores measured at the study site with the scores measured by our central master psychometric raters. Dr. Javitt will provide some insights into the quality metrics we are observing.

我很高興地宣布，我們的臨床試驗現已在 20 名患者中進行，並已獲得預期的數據讀數。我們現在正在建立廣泛的研究基地，預計我們的合作夥伴將資助更大規模的第三階段計劃。更重要的是，我們看到了有希望的質量跡象，在研究地點測量的藥物依從性為 90%，抑鬱分數與我們的中央心理測量大師測量的分數同時為 94%。 Javitt 博士將對我們正在觀察的質量指標提供一些見解。

The Alvogen partnership affords us an opportunity to explore new and broader indications for NRX-101. Because we completed our Phase 3 commercial manufacturing program in Q1, we are able to seamlessly introduce these indications to FDA and have more than 1 million doses of medicine in the warehouse with which to initiate new programs. Specifically, we are exploring the use of NRX-101 in chronic pain and post-traumatic stress disorder.

Alvogen 合作夥伴關係為我們提供了探索 NRX-101 新的更廣泛適應症的機會。由於我們在第一季度完成了第 3 階段的商業生產計劃，因此我們能夠無縫地將這些適應症引入 FDA，並在倉庫中擁有超過 100 萬劑藥物，可用於啟動新計劃。具體來說，我們正在探索 NRX-101 在慢性疼痛和創傷後應激障礙中的用途。

Jonathan, would you review the science results achieved during Q2 and reflect on our near-term goals?

喬納森，您能否回顧一下第二季度取得的科學成果並反思我們的近期目標？

Thank you, Steve. So as Steve shared with all of you on the phone, our near term priority remains the delivery of data for NRX-101 in bipolar depression with suicidality, sufficient to trigger the first $10 million milestone payment in our partnership agreement.

謝謝你，史蒂夫。因此，正如Steve 在電話中與大家分享的那樣，我們近期的首要任務仍然是提供NRX-101 治療伴有自殺傾向的雙相抑鬱症的數據，足以觸發我們合作協議中第一筆1000 萬美元的里程碑付款。

As you know, we're the first pharmaceutical company to enroll patients with suicidal bipolar depression in a clinical trial of a potentially life-saving oral medicine. These are patients who have been excluded from the clinical trials of all previous anti-depressant drugs. The high-risk nature of this population has required us to take a high level of caution in recruiting, selecting, and monitoring the care of these vulnerable patients.

如您所知，我們是第一家招募患有自殺性雙相抑鬱症患者參加可能挽救生命的口服藥物臨床試驗的製藥公司。這些患者已被排除在之前所有抗抑鬱藥物的臨床試驗之外。該人群的高風險性質要求我們在招募、選擇和監測這些弱勢患者的護理時必須高度謹慎。

In March, we advised you that the Independent Data Safety Monitoring Board identified no safety concerns and no futility. And now we're pleased to share with you that no unexpected serious adverse events have occurred in this high-risk population since that time.

三月份，我們通知您，獨立數據安全監控委員會沒有發現任何安全問題，也沒有發現任何無效的信息。現在我們很高興與您分享，自那時以來，這一高危人群中沒有發生意外的嚴重不良事件。

More importantly, clinical trials in psychiatry succeed or fail based on patient compliance with study medicine and the consistency with which depression and other key endpoints are measured from one study to another. And that the things I'm about to talk about are scientifically complex. We've posted a paper to the free-print service, which are free to read and reflect on what I'm about to say.

更重要的是，精神病學臨床試驗的成功或失敗取決於患者對研究藥物的依從性以及一項研究與另一項研究測量抑鬱症和其他關鍵終點的一致性。我要談論的事情在科學上是複雜的。我們已經在免費打印服務上發布了一篇論文，您可以免費閱讀並思考我將要說的內容。

So the quality metrics we're seeing in terms of study retention, safety, medication compliance, and rating reliability give us added confidence that the trial in which we are engaged has the potential to be submitted for drug registration should we prove efficacy. In other words, we don't know that the drug is going to work, but we do have increased confidence that we're measuring the results of the trial in such a way that we will be able to identify efficacy if it's there.

因此，我們在研究保留、安全性、用藥依從性和評級可靠性方面看到的質量指標讓我們更有信心，如果我們證明療效，我們參與的試驗有可能提交藥物註冊。換句話說，我們不知道這種藥物是否會起作用，但我們確實更有信心，我們正在以這樣的方式衡量試驗結果，以便我們能夠確定藥物是否有效。

We track the execution of this trial in a number of ways on a daily and weekly basis. Today, I'd like to share the results to date from three of the key metrics we evaluate namely compliance with the prescribed treatment; concordance of efficacy evaluations, otherwise known as inter-rater reliability conducted at the study sites compared to those conducted by the central raters at our company; and lastly, patient enrollment.

我們每天和每週通過多種方式跟踪該試驗的執行情況。今天，我想分享我們評估的三個關鍵指標的迄今為止的結果，即對處方治療的依從性；與我們公司的中央評估者進行的評估相比，在研究地點進行的功效評估（也稱為評估者間可靠性）的一致性；最後是患者登記。

So first, treatment compliance. So far in our trials, we've seen greater than 90% compliance with patients prescribed regimen as measured by pill counts at patient visits. We're encouraged by the high level of compliance as we believe this is key to patients experiencing relief from their symptoms.

首先，治療依從性。到目前為止，在我們的試驗中，根據患者就診時的藥丸計數來衡量，我們發現患者對處方治療方案的依從性超過 90%。我們對高水平的依從性感到鼓舞，因為我們相信這是患者症狀緩解的關鍵。

Now let's talk about concordance or inter-rater reliability. Psychiatry trial is it's either fail based on their ability to control the accuracy with which the endpoints of the trial are measured. In our case, those endpoints are relief from depression and relief from suicidality.

現在我們來談談一致性或評估者間的可靠性。精神病學試驗的失敗取決於他們控制試驗終點測量準確性的能力。在我們的案例中，這些終點是抑鬱症的緩解和自殺傾向的緩解。

During the first quarter of 2023, we refined our ability to validate the psychometric ratings that are used to assess those efficacy endpoints. We rely on a team of veteran psychometric graders, master's level or PhD, who both train the raters at the independent study sites and rate and monitor the technical quality of each rating.

在 2023 年第一季度，我們改進了驗證用於評估這些功效終點的心理測量評級的能力。我們依靠一支由經驗豐富的心理測量評分員（碩士或博士）組成的團隊，他們在獨立研究地點對評分員進行培訓，並對每個評分的技術質量進行評分和監控。

In other words, we get an audio file of each and every psychometric rating from the study sites and our in-house raters. We review that information to see whether they agree with the information obtained by the study site.

換句話說，我們從研究網站和我們的內部評估者那裡獲得每個心理測量評級的音頻文件。我們審查這些信息，看看他們是否同意研究網站獲得的信息。

We set a standard that requires the measurements reported from study sites on a patient-by-patient basis to be within 3 points of the master raters score on the standard 60-point Montgomery-Åsberg Depression Rating Scale or MADRS. This rating scale is the primary efficacy endpoints that FDA has required for all recently approved antidepressant drugs.

我們制定了一個標準，要求研究中心逐個患者報告的測量結果與標準 60 分蒙哥馬利-安斯伯格抑鬱量表 (MADRS) 的主評分者評分相差在 3 分以內。該評級量表是 FDA 對所有最近批准的抗抑鬱藥物所要求的主要療效終點。

Now the 3-point standard we prespecified in our protocol is substantially stricter than the looser 6-point standard recommended in the literature. But we felt it was essential to reducing site-to-site variables that diminishes the statistical reliability of psychiatry studies.

現在，我們在協議中預先指定的 3 點標準比文獻中推薦的更寬鬆的 6 點標準要嚴格得多。但我們認為減少站點間變量至關重要，因為這些變量會降低精神病學研究的統計可靠性。

In fact, people have often asked how can we obtain a statistically significant endpoint in the STABIL-B study with such a small population? And we attribute that to really tight measurements around those endpoints with very low variance to be accounted for.

事實上，人們經常問我們如何才能在如此小的人群中獲得具有統計顯著性的 STABIL-B 研究終點？我們將其歸因於圍繞這些端點的非常嚴格的測量，並且需要考慮的方差非常低。

So we also set a standard of 90% or better inter-rater reliability, which is the measure of what percent of ratings meet that 3-point standard. Today, we've posted a research report or blinded results from the first 50 patients enrolled in our clinical trial and interviewed in their primary spoken language, documenting 94% inter-rater reliability across study sites.

因此，我們還設定了 90% 或更高的評分者間可靠性標準，這是衡量滿足 3 分標準的評分百分比的標準。今天，我們發布了一份研究報告或來自前 50 名參加我們臨床試驗並以他們的主要口語進行訪談的患者的盲法結果，記錄了各個研究中心 94% 的評估者間可靠性。

In other words, we have no idea who is on drug and who's on lurasidone. All we know is how the ratings obtained in the study site stacks up against the ratings obtained from the same patients, same audio files, by our master raters. This finding substantially exceeds their pre-specified baseline requirements and also exceeds the inter-rater reliability that's routinely published in the literature of the trials. We believe that this rigorous approach to measuring our primary endpoints is key to being able to successfully prove efficacy in our clinical trials should there be efficacy to prove.

換句話說，我們不知道誰在吸毒，誰在服用魯拉西酮。我們所知道的是，在研究網站中獲得的評級如何與我們的主評級員從相同患者、相同音頻文件中獲得的評級進行比較。這一發現大大超出了他們預先指定的基線要求，也超出了試驗文獻中常規發布的評估者間的可靠性。我們相信，如果有療效需要證明，這種嚴格的測量主要終點的方法是能夠在臨床試驗中成功證明療效的關鍵。

In order to meet our safety objectives, we need the ability to recruit substantial number of patients over a short period of time. As we previously noted in April 2023, we contracted with 1nHealth to initiate a recruitment campaign that may cover up to 45 states in the US to recruit sufficient patients for our Phase 3 program.

為了實現我們的安全目標，我們需要能夠在短時間內招募大量患者。正如我們之前在 2023 年 4 月指出的那樣，我們與 1nHealth 簽訂了合同，啟動了一項招募活動，該活動可能覆蓋美國多達 45 個州，以便為我們的第 3 階段計劃招募足夠的患者。

The company has similarly broadened its previously announced relationship with Science 37, a CRO that's conducting decentralized clinical trials to enroll participants identified by the 1nHealth initiatives and to randomize them to be treated within the broadened clinical trials.

該公司同樣擴大了之前宣布的與 Science 37 的關係，Science 37 是一家 CRO，正在進行分散的臨床試驗，以招募 1nHealth 計劃確定的參與者，並將他們隨機分配到擴大的臨床試驗中接受治療。

So let me explain that process. In most clinical trials, you set up study sites in particular locations. Those study sites recruit patients. They treat patients. They measure the results. But somebody who lives to 100 miles or 50 miles away from those study sites is really unable to participate.

讓我解釋一下這個過程。在大多數臨床試驗中，您會在特定地點設置研究中心。這些研究中心招募患者。他們治療病人。他們衡量結果。但居住在距這些研究地點 100 英里或 50 英里的地方的人確實無法參加。

Science 37 has the ability to recruit patients nearly anywhere in the country and send a team of nurses to their door in order to administer the investigational medicine, in order to measure the endpoints of the study. So that our dependence on brick-and-mortar study sites is substantially diminished.

Science 37 能夠在全國幾乎任何地方招募患者，並派出一組護士上門進行研究藥物的管理，從而衡量研究的終點。這樣我們對實體研究場所的依賴就大大減少了。

And now, 1nHealth has additionally engaged The Mighty, a voice-of-a-patient organization with national reach to publicize the clinical trial to their 800,000-plus subscribers, who've indicated a personal focus on bipolar depression and suicidality. And all of you on the phone are welcome to read the latest press articles that The Mighty is sharing with the bipolar community. Based on these broad coordinated efforts, we expect that data will be available near year end of 2023 to meet the Alvogen milestone.

現在，1nHealth 還聘請了 The Mighty（一家具有全國影響力的患者之聲組織）向其超過 800,000 名訂閱者宣傳該臨床試驗，這些訂閱者表示個人對躁鬱症和自殺傾向的關注。歡迎所有打電話的人閱讀 The Mighty 與躁鬱症社區分享的最新新聞文章。基於這些廣泛的協調努力，我們預計將在 2023 年底前提供數據，以實現 Alvogen 里程碑。

As you know, we began talking to public investors about NRX-101 in March 2022 on the tail of the COVID pandemic. And what we've explained the potential impact of our combined formulation of D-cycloserine and lurasidone for bipolar depression, it's also important to recognize the broader applications of this drug class combination.

如您所知，我們於 2022 年 3 月新冠大流行結束後開始與公眾投資者討論 NRX-101。我們已經解釋了 D-環絲氨酸和魯拉西酮聯合製劑對雙相抑鬱症的潛在影響，認識到這種藥物組合的更廣泛應用也很重要。

At NRX-101, we discover the unique synergies between NMDA and 5-HT2A-targeted drugs, those being two different chemical receptors in the brain. Specifically that each component effectively block the potential adverse events effect of the other, creating a potent new therapy with an advantageous safety profile. Additionally, we've identified and patented the critical doses at which D-cycloserine may be effective in various conditions.

在 NRX-101，我們發現 NMDA 和 5-HT2A 靶向藥物之間的獨特協同作用，它們是大腦中的兩種不同的化學受體。具體來說，每個成分都能有效阻止另一個成分潛在的不良事件影響，從而創造出一種具有有利安全性的有效新療法。此外，我們還確定了 D-環絲氨酸在各種條件下可能有效的關鍵劑量併申請了專利。

These discoveries are at the core of our company and at the core of our NMDA platform. These discoveries have resulted in a portfolio of 90 patents around the world, 48 of which have now been issued related to the treatment of bipolar depression, major depressive disorder, PTSD, and other central nervous system conditions.

這些發現是我們公司的核心，也是我們 NMDA 平台的核心。這些發現在全球範圍內產生了 90 項專利，其中 48 項現已授權，涉及雙相抑鬱症、重度抑鬱症、創傷後應激障礙 (PTSD) 和其他中樞神經系統疾病的治療。

Now the Alvogen agreement anticipates that NRx will develop additional products containing D-cycloserine or other NMDA antagonists in combination with one or more antidepressants or anti-psychotic ingredients for use outside the field of bipolar depression with suicidality, such as chronic pain with or without depression and post-traumatic stress disorder or PTSD.

現在，Alvogen 協議預計NRx 將開發含有D-環絲氨酸或其他NMDA 拮抗劑與一種或多種抗抑鬱藥或抗精神病成分組合的其他產品，用於伴有自殺傾向的雙相抑鬱症領域之外，例如伴有或不伴有抑鬱症的慢性疼痛和創傷後應激障礙或創傷後應激障礙。

Last week, we announced the licensure of Professor Apkarian, carrying patent, for the use of D-cycloserine in the treatment of chronic pain therapy. There are approximately 7 million Americans who live with bipolar disorder and episodes of depression. In contrast, more than 50 million Americans live with chronic pain.

上週，我們宣布獲得 Apkarian 教授使用 D-環絲氨酸治療慢性疼痛的專利許可。大約有 700 萬美國人患有雙相情感障礙和抑鬱症。相比之下，超過 5000 萬美國人患有慢性疼痛。

Just as those with bipolar depression, suicidality have no approved treatments other than electric shock therapy. Those who live with chronic pain are frequently dependent on opioid-based medications; the risks of which have become tragically visible to all over the past few years.

就像雙相抑鬱症患者一樣，除了電擊療法之外，自殺傾向沒有經過批准的治療方法。那些患有慢性疼痛的人經常依賴阿片類藥物；過去幾年，其風險已為所有人所悲慘地認識到。

Just a few weeks ago, the White House announced that 165,000 Americans died from opioids annually. We've now posted a paper to the scientific literature, which you can see on our website, documenting more than 20 years of research, which demonstrates the extensive nonclinical and early clinical evidence that D-cycloserine interrupts the pain pathway at each step between the peripheral pain sensors and the central nervous system while potentially decreasing craving for opioids and those who are afflicted with chronic pain.

就在幾週前，白宮宣布每年有 165,000 名美國人死於阿片類藥物。我們現在在科學文獻中發布了一篇論文，您可以在我們的網站上看到，該論文記錄了20 多年的研究，證明了廣泛的非臨床和早期臨床證據，表明D-環絲氨酸會中斷疼痛通路之間的每一步。外周疼痛傳感器和中樞神經系統，同時可能減少對阿片類藥物和患有慢性疼痛的人的渴望。

We've recently published peer-reviewed studies documenting that NRX-101 is not neurotoxic and is not addictive. We believe that chronic pain affords a unique opportunity for NRX-101 and for our shareholders.

我們最近發表的同行評審研究表明，NRX-101 不具有神經毒性，也不具有成癮性。我們相信，慢性疼痛為 NRX-101 和我們的股東提供了獨特的機會。

When we began our work in bipolar depression, opioids were a predominant and widely accepted treatment for chronic pain. At that time, market wisdom suggested that non-addictive, innovative, analgesic drugs could not compete effectively with generic opioids.

當我們開始治療雙相抑鬱症時，阿片類藥物是治療慢性疼痛的主要且被廣泛接受的治療方法。當時，市場智慧表明，非成癮性創新鎮痛藥物無法與仿製阿片類藥物有效競爭。

Today, the situation is quite different. Today, an overwhelming shift in public health policy and public awareness, as reflected in the popular press, recent television series, and multi-jurisdictional litigation, documents a widespread movement against the use of opioids and creates a unique opportunity for non-addictive, non-neurotoxic treatments for chronic pain, an established $72 billion market that is expected to grow to more than $100 billion by 2030.

今天，情況已大不相同。如今，公共衛生政策和公眾意識發生了壓倒性的轉變，正如大眾媒體、最近的電視連續劇和多司法管轄區訴訟所反映的那樣，記錄了反對使用阿片類藥物的廣泛運動，並為非成癮性、非成癮性、非成癮性人群創造了獨特的機會。 -慢性疼痛的神經毒性治療，這是一個價值 720 億美元的成熟市場，預計到 2030 年將增長到超過 1000 億美元。

Of key importance is the recognition by the US Department of Defense of the 2016 study published by Northwestern University Research Group that identified a statistically significant reduction in pain scores at a 400-milligram daily dose of D-cycloserine. That's the threshold dose that also predicted in our patent portfolio. The DOD acted on this finding by funding a $5 million congressionally directed medical research program award to Northwestern University to study D-cycloserine in several hundred patients with chronic pain.

至關重要的是美國國防部對西北大學研究小組 2016 年發表的研究的認可，該研究發現每天服用 400 毫克劑量的 D-環絲氨酸可顯著降低疼痛評分。這也是我們的專利組合中預測的閾值劑量。國防部根據這一發現採取了行動，向西北大學提供了 500 萬美元國會指導的醫學研究項目資助，以研究 D-環絲氨酸對數百名慢性疼痛患者的作用。

As shown on clinicaltrials.gov, patient recruitment in this trial is complete and study results are anticipated in the near future. Thus, a large public investment in chronic pain therapy, completely non-dilutive to our shareholders, using the key ingredients of our drug, namely D-cycloserine, already has the potential to provide a rapid path to drug approval for the efficacy be shown.

如 ClinicalTrials.gov 上所示，該試驗的患者招募已完成，預計研究結果將在不久的將來出現。因此，對慢性疼痛治療的大量公共投資，完全不會稀釋我們的股東，使用我們藥物的關鍵成分，即 D-環絲氨酸，已經有可能為藥物批准提供快速途徑，以顯示療效。

The lurasidone component of our drug may also independently treat chronic pain. As previously announced, we've completed our Phase 3 and commercial manufacturing program for NRX-101. This week, we're opening an investigational new drug file with the FDA for use of NRX-101 to treat chronic pain. The rationale for treatments of chronic pain with D-cycloserine is outlined in the review article that we've recently posted and is on our website and in the 2016 scientific paper published by Professor Schnitzer of carrying on their cohorts.

我們藥物中的魯拉西酮成分也可以獨立治療慢性疼痛。正如之前宣布的，我們已經完成了 NRX-101 的第三階段和商業製造計劃。本週，我們將向 FDA 開放一份使用 NRX-101 治療慢性疼痛的研究性新藥文件。我們最近發布的評論文章、我們的網站以及 Schnitzer 教授發表的 2016 年科學論文中概述了用 D-環絲氨酸治療慢性疼痛的基本原理。

In brief, D-cycloserine, which act in NMDA antagonist drug above threshold doses, has demonstrated extensive nonclinical and early clinical efficacy in: one, decreasing the response to no susceptible pain, that is the pain that's triggered by pain receptors in the body; and two, decreasing craving for opioid drugs with evidence that DCS is both non-addictive and non-neurotoxic.

簡而言之，D-環絲氨酸在高於閾值劑量的NMDA 拮抗劑藥物中發揮作用，已在以下方面表現出廣泛的非臨床和早期臨床功效：第一，減少對非敏感疼痛的反應，即由體內疼痛受體觸發的疼痛；第二，減少對阿片類藥物的渴望，有證據表明 DCS 既不成癮，也不具有神經毒性。

Regarding post-traumatic stress disorder or PTSD, we've previously identified the rationale for treating PTSD with NMDA antagonist drug and shared with you evidence that DCS decreases that pure memory associated with PTSD in nonclinical studies. We plan to investigate NRX-101 in PTSD as an additional indication and to commence planning for that Phase 2 clinical trial in 2023.

關於創傷後應激障礙或 PTSD，我們之前已經確定了用 NMDA 拮抗劑藥物治療 PTSD 的基本原理，並與您分享了非臨床研究中 DCS 會降低與 PTSD 相關的純記憶的證據。我們計劃將 NRX-101 作為 PTSD 的額外適應症進行研究，並於 2023 年開始計劃 2 期臨床試驗。

In summary, I believe our progress this quarter solidifies our ability to reach patients with suicidal bipolar depression. While the results of our ongoing trial remain blinded, we've shown scientific evidence that the trial is being effectively executed and rigorously monitored. Additionally, our chronic pain program has expanded the company's market opportunity tenfold and positions the company for future growth with near-term data readouts.

總之，我相信我們本季度取得的進展鞏固了我們接觸自殺性雙相抑鬱症患者的能力。雖然我們正在進行的試驗結果仍然是盲目的，但我們已經提供了科學證據，表明試驗正在有效執行和嚴格監控。此外，我們的慢性疼痛計劃將公司的市場機會擴大了十倍，並通過近期數據讀數為公司未來的增長奠定了基礎。

Our programs address more than $100 billion in market opportunity while serving patients with significant unmet medical needs. As always, I'd like to express my gratitude to the patients, the NRX team, the clinical trial investigators, and most importantly, you, our shareholders for your continued support.

我們的計劃解決了超過 1000 億美元的市場機會，同時為醫療需求未得到滿足的患者提供服務。一如既往，我要向患者、NRX 團隊、臨床試驗研究人員表示感謝，最重要的是，感謝您，我們的股東，感謝您的持續支持。

Seth Van Voorhees will now discuss our financial performance.

Seth Van Voorhees 現在將討論我們的財務業績。

Thank you, Jonathan, and good afternoon, everyone. I will now review the highlights from our second-quarter 2023 financial results. In June, the company raised $6.3 million in a registered direct offering and negotiated an amendment with Streeterville Capital, the company's current debt holder, to address the company's current debt facility to best support the ongoing needs of the clinical trial. The amendment targets reduced monthly redemptions of the loan to $400,000 per month through year-end 2023.

謝謝喬納森，大家下午好。我現在將回顧 2023 年第二季度財務業績的要點。 6 月，該公司通過註冊直接發行籌集了630 萬美元，並與該公司當前債務持有人Streeterville Capital 協商了一項修正案，以解決該公司當前的債務融資問題，以最好地支持臨床試驗的持續需求。該修正案的目標是，到 2023 年底，每月償還貸款額減少至 40 萬美元。

For the three months ended June 30, 2023, NRX recorded $3.9 million of R&D expenses compared to $3 million for the three months ended June 30, 2022. The increase is related primarily to an increased clinical trial enrollment in our ongoing Phase 2b/3 trial.

截至2023 年6 月30 日的三個月，NRX 的研發費用為390 萬美元，而截至2022 年6 月30 日的三個月為300 萬美元。這一增長主要與我們正在進行的2b/3期試驗的臨床試驗註冊人數增加有關。

For the same three-month period, we recorded a 38% reduction in general and administrative expenses from $6.6 million in the second quarter of 2022 to $4.1 million for the three months ended June 30, 2023. The decrease of $2.5 million is related primarily to decrease in legal, insurance, and accounting costs.

在同一三個月期間，我們的一般和管理費用減少了38%，從2022 年第二季度的660 萬美元減少到截至2023 年6 月30 日止三個月的410 萬美元。減少250 萬美元主要與法律、保險和會計成本減少。

The six-month period from January through June of 2023 similarly shows decreased expenditures as reflected in our financial statement compared to the prior year.

正如我們的財務報表所反映的，與上一年相比，2023 年 1 月至 6 月的六個月期間支出也有所減少。

As of June 30, 2023, we had $15 million in cash and cash equivalents. These working capital assets are expected to fund the company's operations through the fourth quarter of this year, which is the expected delivery of data for our Phase 2b/3 trial. Additionally, we are evaluating operational efficiencies to extend this runway.

截至 2023 年 6 月 30 日，我們擁有 1500 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運營提供資金直至今年第四季度，這是我們 2b/3 期試驗的預期數據交付。此外，我們正在評估延長這條跑道的運營效率。

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

說到這裡，我將把它轉回給史蒂夫做結束語。史蒂夫？

Thanks, Seth. 2023 has been incredibly productive so far and we look forward to advancing our NMDA platform in general and specifically our NRX-101 program in suicidal bipolar depression with our partners at Alvogen, as well as our very exciting chronic pain program all in the near term.

謝謝，塞思。到目前為止，2023 年已經取得了令人難以置信的成果，我們期待著與Alvogen 的合作夥伴一起推進我們的NMDA 平台，特別是我們在自殺性雙相抑鬱症方面的NRX-101 項目，以及我們非常令人興奮的慢性疼痛項目，所有這些都在短期內完成。

We believe that NRX-101 is a potentially life-saving medicine that could change the treatment paradigm for a wide range of serious and life-threatening conditions, which is the driving force behind our mission of meeting the needs of these underserved patients.

我們相信 NRX-101 是一種潛在的救命藥物，可以改變多種嚴重和危及生命的疾病的治療模式，這是我們滿足這些服務不足的患者需求的使命背後的驅動力。

With the shared commitment of our investors, our team, and our researchers, we aim to bring hope to life for the millions of patients who may benefit from our unique products.

在我們的投資者、團隊和研究人員的共同承諾下，我們的目標是為數百萬可能受益於我們獨特產品的患者帶來希望。

Operator, we are ready to take questions from the audience.

接線員，我們準備好回答觀眾的問題。

(Operator Instructions)

（操作員說明）

Operator, we've received a couple of written questions that I'll proceed with now.

接線員，我們收到了幾個書面問題，我現在將繼續處理。

This one is for the company. How is the partnership with Alvogen going so far?

這個是給公司的。目前與 Alvogen 的合作進展如何？

I think it is going very well. We had a joint executive meeting in person last week. The teams are melding well. I think it's going very well.

我認為一切進展順利。上週我們親自召開了一次聯合執行會議。球隊融合得很​​好。我認為一切進展順利。

Thanks. This one is for Dr. Javitt. How potent do you believe D-cycloserine in NRX-101 may be in treatment of chronic pain?

謝謝。這是給賈維特博士的。您認為 NRX-101 中的 D-環絲氨酸治療慢性疼痛的功效如何？

Please let me hear the question again. I didn't read the second word.

請讓我再聽一次這個問題。我沒讀第二個字。

Sorry. How potent do you believe D-cycloserine in NRX-101 may be in chronic pain?

對不起。您認為 NRX-101 中的 D-環絲氨酸對慢性疼痛的療效如何？

Well, if you look at the 2016 publication by Schnitzer and of carrying on their coworkers, the reduction seen in treating chronic pain was certainly deemed clinically meaningful. It's a reduction that is probably larger than what you can obtain from non-opioid pain medicine and may even be comparable to what you can obtain from safe doses of opioid medicines.

好吧，如果你看看 Schnitzer 及其同事在 2016 年發表的文章，就會發現治療慢性疼痛的減少肯定被認為具有臨床意義。這種減少量可能大於從非阿片類止痛藥中獲得的減少量，甚至可能與從安全劑量的阿片類藥物中獲得的減少量相當。

We're going to know an awful lot more when the DOD trial reads out because that's a couple of hundred patients treated over 12 weeks. But there's reason to hope that NMDA antagonist drug may be quite potent. And in fact, anesthesiologists already treat chronic pain with IV ketamine. But of course, recognize that to get IV ketamine, you've got to be in a hospital environment. It's not a simple process.

當國防部試驗結果出來時，我們將會了解更多信息，因為在 12 週內有數百名患者接受了治療。但我們有理由相信 NMDA 拮抗劑藥物可能非常有效。事實上，麻醉師已經用靜脈注射氯胺酮來治療慢性疼痛。但當然，要認識到要獲得靜脈注射氯胺酮，您必須在醫院環境中。這不是一個簡單的過程。

But there's no question that an NMDA antagonist drug block the pain pathway at each step. There are three nerve cells that go between your fingertip and your frontal cortex. And at each step, the connection between nerve cells is regulated by the NMDA receptor.

但毫無疑問，NMDA 拮抗劑藥物會阻斷疼痛通路的每一步。您的指尖和額葉皮層之間存在三個神經細胞。每一步，神經細胞之間的連接都受到 NMDA 受體的調節。

Another question. Can you talk a little bit about the patients who are going into the Phase 3 study? How they're doing? And are they continuing through the trial and how that's going sort of in the big picture?

另一個問題。您能談談即將進入 3 期研究的患者嗎？他們怎麼樣？他們是否會繼續進行審判？總體情況如何？

Well, I think we shared just about everything we can in the context of a randomized double-blind trial. We're steadily enrolling patients. We're doing it with a great degree of caution.

嗯，我認為我們在隨機雙盲試驗的背景下分享了我們所能分享的一切。我們正在穩步招募患者。我們在做這件事時非常謹慎。

So for instance, a study site will identify if patient is potentially eligible. They'll review the eligibility criteria with us ahead of enrolling the patient. And then they'll submit the audio files of the MADRS score, rating session, the suicidality rating sessions.

例如，研究中心將確定患者是否有潛在資格。他們將在招募患者之前與我們一起審查資格標準。然後他們將提交 MADRS 評分、評級會議、自殺評級會議的音頻文件。

And our in-house master raters will validate those floors before somebody gets into the clinical trial. So I think we're being as careful as we can possibly be about who gets them and how the primary and secondary endpoints are ascertained once they're in the trial.

我們的內部主評估員將在有人進入臨床試驗之前驗證這些底線。因此，我認為我們會盡可能謹慎地關注誰獲得這些藥物，以及一旦進入試驗，如何確定主要和次要終點。

Very good. Last written question that we've received. Can you talk about the genesis of the Department of Defense study in their -- with D-cycloserine and the genesis of a larger trial, the bigger picture around that?

非常好。我們收到的最後一個書面問題。您能談談國防部研究 D-環絲氨酸的起源以及更大規模試驗的起源嗎？

Well, we had nothing to do with the Department of Defense study. So Dan Javitt, the Co-Founder of this company, began engaging with D-cycloserine as a potential anti-depressant drug around 2004, professor of carrying and his coworkers, similarly, began studying the potential for D-cycloserine to be used to treat chronic pain.

好吧，我們與國防部的研究無關。因此，該公司的聯合創始人Dan Javitt 在2004 年左右開始研究D-環絲氨酸作為一種潛在的抗抑鬱藥物，同樣，Carry 教授和他的同事也開始研究D-環絲氨酸用於治療抑鬱症的潛力。慢性疼痛。

They've developed a substantial basic science base, which is cited in the review paper that we've posted for you. And they perform that first 40 person trial, which yielded the positive results. The trial itself was not deemed to have met its primary endpoint because they studied patients at 50 milligrams, 100 milligrams, 200 milligrams, and 400 milligrams of D-cycloserine, and they didn't see a benefit across all of those doses. They saw statistically significant benefit only at the highest dose.

他們已經建立了堅實的基礎科學基礎，我們在為您發布的評論論文中引用了這些基礎科學基礎。他們進行了首次 40 人試驗，取得了積極的結果。該試驗本身未被認為已達到其主要終點，因為他們研究了服用 50 毫克、100 毫克、200 毫克和 400 毫克 D-環絲氨酸的患者，並且沒有發現所有這些劑量都有益處。他們僅在最高劑量下才看到統計上顯著的益處。

They reported that out in 2016. And they applied to the Department of Defense who responded with a $5 million grant to do a larger confirmatory trial. And we don't know any more about that trial. It's available to the public; you can read about it on clinicaltrials.gov.

他們於 2016 年報告了這一情況。他們向國防部申請了 500 萬美元的撥款，以進行更大規模的驗證性試驗。我們對那次審判一無所知。它向公眾開放；您可以在 ClinicalTrials.gov 上閱讀相關內容。

But we do know that data collection is complete and the study is anticipating a readout this year. So we're very excited that the study happened. And we're making plans to initiate registration study should that study yield a positive readout.

但我們確實知道數據收集已經完成，並且該研究預計將於今年公佈。所以我們對這項研究的發生感到非常興奮。我們正在計劃啟動註冊研究，如果該研究產生積極的結果。

Thank you.

謝謝。

Ed Woo, Ascendiant Capital.

艾德·吳，Ascendian Capital。

Yeah. Congratulations on the progress. My question is on the partnership that you guys found recently with Lotus and Alvogen. A lot of this obviously very strong in Asia. How much efforts are you going to be doing to expand these drugs into Asia? Or is it pretty much just focused on US approval first before you move into Asia? Thank you.

是的。祝賀取得的進展。我的問題是關於你們最近與 Lotus 和 Alvogen 建立的合作夥伴關係。其中很多在亞洲顯然非常強大。您將付出多少努力將這些藥物擴展到亞洲？或者在進入亞洲之前，它只是首先關注美國的批准？謝謝。

Thanks for that question, Ed. I think it's significant that Lotus is a full partner in this because they are very strong on in Asia. I think as we go through into the Phase 3 trial and get closer to commercialization, some of those decisions will be made.

謝謝你提出這個問題，艾德。我認為路特斯成為這方面的全面合作夥伴意義重大，因為他們在亞洲非常強大。我認為，當我們進入第三階段試驗並接近商業化時，將會做出其中一些決定。

But I know that, for example, in our meetings on the commercial side, Lotus is always present at the table. And I think that bodes well for a major effort in Asia as well as in the US. That said, of course, the US is a much larger market for the product.

但我知道，例如，在我們的商業方面的會議中，Lotus 總是出現在會議桌上。我認為這對於亞洲和美國的重大努力來說是個好兆頭。當然，美國是該產品更大的市場。

Great. Well, thank you for answering my questions, and I wish you guys good luck. Thank you.

偉大的。好的，謝謝您回答我的問題，祝大家好運。謝謝。

Thank you.

謝謝。

(Operator Instructions)

（操作員說明）

This concludes our question-and-answer session. I would like to turn the conference back over to Mr. Steve Willard for any closing remarks. Please go ahead, sir.

我們的問答環節到此結束。我想將會議轉回史蒂夫·威拉德先生髮表閉幕詞。請繼續，先生。

Thank you very much and we very much appreciate your interest in NRX Pharmaceuticals. We thank you for listening to our presentation on this very exciting quarter. And we hope that you will follow us closely in the weeks and months to come. Thank you very much.

非常感謝您，我們非常感謝您對 NRX Pharmaceuticals 的興趣。我們感謝您聆聽我們關於這個激動人心的季度的演講。我們希望您在未來幾周和幾個月內密切關注我們。非常感謝。

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。