NRX Pharmaceuticals Inc (NRXP) 2023 Q1 法說會逐字稿

Good day, everyone, and welcome to the NRX Pharmaceuticals' first-quarter 2023 earnings conference call. (Operator Instructions)

大家好，歡迎參加 NRX Pharmaceuticals 2023 年第一季度收益電話會議。 （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 Suzanne Messere with Stern Investor Relations. Please go ahead.

我現在想將會議轉交給 Stern 投資者關係部的 Suzanne Messere。請繼續。

Thank you, Vashnavi. 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. 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，瓦什納維。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。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。

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 earlier today and in the company's Form 10-K, which was re-filed on May 1, which may be accessed from the Investors page of the NRX Pharmaceuticals, Inc. website.

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。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於 5 月 1 日重新提交的 10-K 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 from NRX Pharmaceuticals are Stephen Willard, Chief Executive Officer; and Seth Van Voorhees, Chief Financial Officer and Treasurer. Stephen will provide a summary of the company's progress, Seth will review the company's financial results, and then Stephen will review upcoming milestone before making closing comments.

今天與我一起參加 NRX Pharmaceuticals 的還有首席執行官 Stephen Willard；以及首席財務官兼財務主管 Seth Van Voorhees。斯蒂芬將提供公司進展的摘要，賽斯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。

Following their prepared remarks, Stephen and Seth will be joined by Jonathan Javitt, the company's Chief Scientist; and Matthew Duffy, the company's Chief Business Officer to address investor questions.

在斯蒂芬和賽斯發表準備好的講話後，該公司的首席科學家喬納森·賈維特 (Jonathan Javitt) 將加入其中。該公司首席商務官 Matthew Duffy 回答了投資者的問題。

I will now turn the call over to Stephen.

我現在將把電話轉給斯蒂芬。

Thank you, Suzanne. Good morning, everyone, and thank you for joining us to discuss our continued success as we advance our pipeline of innovative therapeutics for patients facing psychiatric disorders with great unmet need, including treatment-resistant suicidal bipolar depression, post-traumatic stress disorder, and potentially chronic pain related to depression.

謝謝你，蘇珊娜。大家早上好，感謝您與我們一起討論我們持續取得的成功，我們為面臨巨大未滿足需求的精神疾病患者推進創新療法，包括難治性自殺性雙相抑鬱症、創傷後應激障礙和潛在的精神疾病。與抑鬱症有關的慢性疼痛。

Today, we will discuss first-quarter 2023 results and provide a business update. 2023 is off to a great start as we continue to build our leading brain health franchise, advancing our compelling science, and building long-term value for our shareholders. In recent months, we've made great strides in our clinical trials for our lead product candidate, NRX-101, while continuing to execute on our corporate strategy.

今天，我們將討論 2023 年第一季度業績並提供業務更新。 2023 年是一個良好的開端，我們將繼續打造領先的腦健康專營權，推進令人信服的科學發展，並為股東創造長期價值。近幾個月來，我們的主要候選產品 NRX-101 的臨床試驗取得了巨大進展，同時繼續執行我們的企業戰略。

To summarize, we aligned with the FDA on the chemistry manufacturing and controls of NRX-101, as well as a path to commercial-stage product, and continue to align with the FDA on a potential path for approval of NRX-101 in a Type B meeting.

總而言之，我們在 NRX-101 的化學製造和控制以及商業階段產品的路徑上與 FDA 保持一致，並繼續與 FDA 在批准 NRX-101 的潛在路徑上保持一致乙會議。

We announced encouraging findings of our independent Data Safety and Monitoring Board or DSMB, whose first evaluation of unblinded data identified no safety concerns and subsequent evaluation indicated that no safety or futility signals were reported in the first 50 patients treated, and provided a positive recommendation to continue enrollment. And based on FDA interactions and DSMB findings, we are consolidating our two clinical trials of NRX-101 in suicidal bipolar depression into one study for patients with suicidal treatment-resistant bipolar depression.

我們宣布了獨立數據安全和監測委員會 (DSMB) 的令人鼓舞的發現，該委員會對非盲數據的首次評估未發現任何安全問題，隨後的評估表明，前 50 名接受治療的患者沒有報告安全性或無效信號，並提供了積極的建議繼續報名。根據 FDA 的相互作用和 DSMB 的發現，我們正在將 NRX-101 治療自殺性雙相抑鬱症的兩項臨床試驗合併為一項針對自殺治療抵抗性雙相抑鬱症患者的研究。

I'll begin by reviewing recent progress made for NRX-101 in suicidal treatment-resistant bipolar depression, PTSD, and chronic pain. NRX-101 is a fixed dose combination of D-cycloserine, an NMDA receptor modulator, and lurasidone, a standard-of-care medicine for use in treatment-resistant bipolar depression. There are approximately 7 million people living with bipolar depression in the US and the risk of suicide is very high with this population. Data indicates that 50% or more of these patients will attempt suicide in their lifetime.

首先，我將回顧 NRX-101 在自殺難治性雙相抑鬱症、創傷後應激障礙 (PTSD) 和慢性疼痛方面取得的最新進展。 NRX-101 是 D-環絲氨酸（一種 NMDA 受體調節劑）和魯拉西酮（一種用於治療難治性雙相抑鬱症的標準治療藥物）的固定劑量組合。在美國，大約有 700 萬人患有雙相抑鬱症，這一人群的自殺風險非常高。數據表明，50% 或更多的患者在一生中會嘗試自殺。

However, there are currently no approved medicines for people with suicidal bipolar depression. To our knowledge, NRX is first company to attempt to bring a medicine to people whose only FDA-approved treatment alternative is electroshock therapy. This is a potentially life-saving advance, because antidepressants carry black box warning labels regarding the potential for increased risk of suicide in vulnerable populations. Based on NRX's differentiated therapeutic profile, we believe that we have the potential to address a significant unmet need for patients who are currently underserved by available treatment options.

然而，目前還沒有批准用於自殺性雙相抑鬱症患者的藥物。據我們所知，NRX 是第一家嘗試向 FDA 批准的唯一治療替代方案是電擊療法的患者提供藥物的公司。這是一項可能挽救生命的進步，因為抗抑鬱藥帶有黑框警告標籤，提示弱勢群體自殺風險可能增加。基於 NRX 的差異化治療方案，我們相信我們有潛力解決目前可用治療方案服務不足的患者的重大未滿足需求。

Turning to the science behind NRX-101. NMDA antagonist drugs have been shown to reduce symptoms of depression and suicidal ideation. And neither D-cycloserine nor lurasidone have shown potential for abuse, which is an important consideration when treating psychiatric disorders with suicidal thoughts.

轉向 NRX-101 背後的科學原理。 NMDA 拮抗劑藥物已被證明可以減輕抑鬱症狀和自殺意念。 D-環絲氨酸和魯拉西酮都沒有表現出濫用的可能性，這是治療有自殺念頭的精神疾病時的一個重要考慮因素。

At NRX, we discovered the unique synergy between NMDA and 5-HT2A targeted drugs, as well as the critical dosages at which D-cycloserine may be effective in these conditions. These discoveries resulted in a portfolio of 90 patents around the world, 48 of which have now been issued, relating to the treatment of bipolar depression, major depressive disorder, PTSD, and other central nervous system conditions.

在 NRX，我們發現了 NMDA 和 5-HT2A 靶向藥物之間的獨特協同作用，以及 D-環絲氨酸在這些情況下可能有效的關鍵劑量。這些發現在全球產生了 90 項專利，其中 48 項現已發布，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。

We initially introduced NRX-101 as a drug that showed benefit in conjunction with ketamine in acute care patients, proof-of-concept data from the Phase 2 STABIL-B clinical trial, which administered NRX-101 following stabilization of hospitalized bipolar patients with acute suicidal ideation after treatment with ketamine, demonstrated a highly differentiated therapeutic profile in a patient population with no drug therapy options. Based on this data, the FDA granted breakthrough therapy designation and a special protocol agreement or SPA for NRX-101 in bipolar depression with acute suicidality.

我們最初推出 NRX-101 作為一種藥物，與氯胺酮聯合使用對急性護理患者有益，2 期 STABIL-B 臨床試驗的概念驗證數據，該試驗在住院雙相情感障礙患者病情穩定後給予 NRX-101氯胺酮治療後的自殺意念在沒有藥物治療選擇的患者群體中表現出高度差異化的治療特徵。基於這些數據，FDA 授予 NRX-101 治療伴有急性自殺傾向的雙相抑鬱症的突破性療法稱號和特殊方案協議或 SPA。

In January 2023, the company initiated a Phase 3 registrational clinical trial of NRX-101 for the treatment of severe bipolar depression with acute suicidal ideation and behavior. Based on recent comments from the FDA at a Type B meeting of NRX-101 for hospitalized patients with acute suicidality, this study has been converged with our Phase 2 clinical trial of NRX-101 and bipolar depression with sub-acute suicidal ideation, a study initiated in 2022 for a much broader potential patient population.

2023年1月，該公司啟動了NRX-101的3期註冊臨床試驗，用於治療伴有急性自殺意念和行為的嚴重雙相抑鬱症。根據 FDA 最近在 NRX-101 針對急性自殺住院患者的 B 類會議上的評論，這項研究已與我們的 NRX-101 和具有亞急性自殺意念的雙相抑鬱症的 2 期臨床試驗趨同，這是一項研究於 2022 年啟動，面向更廣泛的潛在患者群體。

This decision was made in March of this year when we announced encouraging findings from our outpatient trial of NRX-101 in the sub-acute population versus lurasidone. Our independent DSMB examined unblinded data from the first 50 patients and found no futility signal at this time in the trial. Similarly, no safety signals were identified in association with NRX-101 and the DSMB recommended that enrollment in the trial continued as planned.

這一決定是在今年 3 月做出的​​，當時我們宣布了 NRX-101 與魯拉西酮在亞急性人群中的門診試驗的令人鼓舞的結果。我們的獨立 DSMB 檢查了前 50 名患者的非盲數據，目前在試驗中沒有發現無效信號。同樣，沒有發現與 NRX-101 相關的安全信號，DSMB 建議繼續按計劃參加試驗。

According to the study's statistical analysis plan, the failure to identify futility requires that an advantage, though not yet a statistically significant advantage, of the investigational drug relative to the comparator treatment must be observed by the DSMB. The newly converged and upgraded Phase 2b/3 clinical trial includes patients with suicidal bipolar depression -- suicidal bipolar patient population, which represents a broader indication. We believe the results of this study could be used in a future registrational filing should the trial prove successful.

根據該研究的統計分析計劃，如果未能確定無效性，則 DSMB 必須觀察到研究藥物相對於比較治療藥物的優勢（儘管尚未具有統計顯著優勢）。新融合和升級的2b/3期臨床試驗包括自殺性雙相抑鬱症患者——自殺性雙相情感障礙患者群體，這代表了更廣泛的適應症。我們相信，如果試驗成功，這項研究的結果可以用於未來的註冊申請。

In this trial, we have focused our outpatient clinical trial first on those of greatest unmet medical needs, specifically those patients who are under care of the physician for bipolar depression and who have ongoing depressive symptoms and active thoughts of self-harm despite treatment of available medicines.

在這項試驗中，我們的門診臨床試驗首先將重點放在那些醫療需求未得到滿足的患者身上，特別是那些因雙相抑鬱症而接受醫生護理的患者，以及儘管接受了現有治療但仍有持續抑鬱症狀和積極自殘想法的患者。藥物。

The objective of this multicenter randomized double-blind controlled potentially registrational study is to demonstrate NRX's ability to significantly improve symptoms of depression and suicidality over six weeks when taken twice a day on a home-use basis. This study has the potential to expand the use of our medicine to the nearly 1 million people who currently suffer from severe depression and suicidal ideation despite expert medical care with currently available medicines. We anticipate that this is a market of approximately $2.2 billion a year.

這項多中心隨機雙盲對照潛在註冊研究的目的是證明 NRX 在家庭每天服用兩次的情況下，在六週內能夠顯著改善抑鬱和自殺症狀。這項研究有可能將我們的藥物的使用範圍擴大到近 100 萬人，儘管他們使用現有藥物進行了專家醫療護理，但目前仍患有嚴重抑鬱症和自殺意念。我們預計這是一個每年約 22 億美元的市場。

The company believes that this strategy to converge the ongoing clinical trials and broaden the indication could enable more patients with suicidal bipolar depression the option of an outpatient therapy in the coming years. Data from the ongoing Phase 2b/3 clinical trials are expected in the fourth quarter of 2023. This broader indication may also up significant advantages in commercialization in the matter consistent with the FDA's recommendations.

該公司相信，這一融合正在進行的臨床試驗並擴大適應症的策略可以使更多患有自殺性雙相抑鬱症的患者在未來幾年內選擇門診治療。正在進行的 2b/3 期臨床試驗的數據預計將於 2023 年第四季度獲得。這一更廣泛的適應症也可能會在符合 FDA 建議的情況下在商業化方面帶來顯著優勢。

Importantly, in January 2023, we also reached alignment with the FDA on our proposed manufacturing plan based on a Type C meeting to review our chemistry, manufacturing, and controls. As a result, NRX is now positioned to conduct registrational trials of NRX-101 and able to make NRX-101 available through expanded access and right-to-drug programs for patients who have exhausted approved treatment options.

重要的是，2023 年 1 月，我們還根據 C 類會議審查我們的化學、製造和控制，就我們提議的製造計劃與 FDA 達成一致。因此，NRX 現在準備進行 NRX-101 的註冊試驗，並能夠通過擴大使用範圍和藥物權計劃，為已用盡批准治療方案的患者提供 NRX-101。

We are excited about this milestone, in particular, as we believe that adopting a commercial-ready manufacturing process at this stage of our development can lead to a more seamless NDA submission, review and approval process under the potential breakthrough therapy designation, without the need for bridging studies.

我們對這一里程碑感到特別興奮，因為我們相信，在我們開發的現階段採用商業化生產工藝可以在潛在突破性療法指定下實現更加無縫的 NDA 提交、審查和批准流程，而無需用於橋樑研究。

During the first quarter of 2023, the company refined its ability to validate the psychometric ratings that are used to assess the efficacy endpoints for the clinical trial. The company relies upon a team of veteran raters who both train independent site raters and monitor the technical quality of each rating. A standard was set of 90% or better concordance between the company's veteran rating team and site raters. This standard was met for all study participants whose ratings were obtained in their primary language. And management believes that this standard can be maintained for the duration of the trial.

2023 年第一季度，該公司改進了驗證用於評估臨床試驗療效終點的心理測量評級的能力。該公司依靠一支經驗豐富的評級員團隊，他們既培訓獨立的網站評級員，又監控每個評級的技術質量。公司的資深評級團隊和網站評級人員之間的一致性設定為 90% 或更高。所有以主要語言獲得評分的研究參與者都符合這一標準。管理層認為，在試驗期間可以維持這一標準。

In April 2023, the company contracted with 1nHealth to initiate a recruitment campaign that may cover up to 45 states in the US to recruit sufficient participants for this enlarged trial. The company has similarly broadened its previously disclosed relationship with Science 37, a contract research organization that conducts decentralized clinical trials, to enroll participants identified by the 1nHealth recruitment initiative and to randomize them to be treated within the broad clinical trial. 1nHealth has additionally engaged a voice-of-the-patient organization with national reach to publicize the clinical trial to the 800,000-plus subscribers who have indicated a focus on bipolar depression and suicidality.

2023年4月，該公司與1nHealth簽訂合同，發起一項可能覆蓋美國多達45個州的招募活動，為這次擴大試驗招募足夠的參與者。該公司同樣擴大了之前披露的與 Science 37 的關係，Science 37 是一家進行分散臨床試驗的合同研究組織，以招募 1nHealth 招募計劃確定的參與者，並將他們隨機分配到廣泛的臨床試驗中接受治療。 1nHealth 還聘請了一家具有全國影響力的患者之聲組織，向超過 80 萬訂閱者宣傳該臨床試驗，這些訂閱者表示關注雙相抑鬱和自殺傾向。

Additionally, last quarter, we continued to work to advance our development plans for NRX-101 in post-traumatic stress disorder or PTSD, another area of high unmet medical need, which is also associated with suicidality. Approximately 9 million individuals in our country experienced PTSD, and one-third have severe PTSD with 10% experiencing suicidality.

此外，上個季度，我們繼續努力推進 NRX-101 在創傷後應激障礙或 PTSD 方面的開發計劃，這是另一個醫療需求未得到高度滿足的領域，也與自殺有關。我國大約有 900 萬人經歷過 PTSD，其中三分之一患有嚴重的 PTSD，其中 10% 有自殺傾向。

Between 17 and 22 members of our armed forces or veterans are lost every day to suicide. Depression and PTSD may be driven by pathways that are similar to those that drive depression and other conditions. However, NMDA antagonist as a class and D-cycloserine, in particular, may have a more specific effect in treatment of PTSD.

每天有 17 至 22 名武裝部隊成員或退伍軍人因自殺身亡。抑鬱症和創傷後應激障礙 (PTSD) 的驅動途徑可能與抑鬱症和其他病症的驅動途徑相似。然而，NMDA拮抗劑作為一類，尤其是D-環絲氨酸，可能在治療PTSD方面具有更特異的作用。

In a preclinical PTSD study, D-cycloserine demonstrated the ability to extinguish reoccurring images of traumatic events, also known as fear memory, in a validated WKY model of PTSD. This model has been similarly used by others to document a PTSD-specific effect of ketamine.

在一項臨床前 PTSD 研究中，D-環絲氨酸在經過驗證的 PTSD WKY 模型中證明了能夠消除創傷事件反復出現的圖像（也稱為恐懼記憶）。其他人也類似地使用該模型來記錄氯胺酮對 PTSD 的特異性作用。

Repeated IV ketamine has also been demonstrated to improve PTSD scores in a randomized controlled trial. Unlike ketamine, however, NRX-101 is not neurotoxic and not addictive, and has not caused psychedelic side effects on clinical trials.

在一項隨機對照試驗中，重複靜脈注射氯胺酮也被證明可以改善創傷後應激障礙 (PTSD) 評分。然而，與氯胺酮不同的是，NRX-101 不具有神經毒性，也不具有成癮性，並且在臨床試驗中未引起迷幻副作用。

We anticipate that our investigational drug will show antidepressant effect in PTSD compared to placebo and we hope that it will demonstrate specific effects on the fear memory components of PTSD and directly reduce symptoms of PTSD itself. Today, there is no approved medicine for these specific PTSD symptoms. We are on track to initiate a study of NRX-101 in PTSD in 2023.

我們預計，與安慰劑相比，我們的研究藥物將在 PTSD 中顯示出抗抑鬱作用，我們希望它能對 PTSD 的恐懼記憶成分產生特定的作用，並直接減輕 PTSD 本身的症狀。目前，還沒有批准的藥物可以治療這些特定的 PTSD 症狀。我們有望於 2023 年啟動 NRX-101 治療 PTSD 的研究。

We are incredibly excited about potential life-saving effect of NRX-101. And in order to support a continued clinical development of these programs, we announced the close of a $2.9 million registered direct offering to support our pipeline efforts, and more specifically, the initiation of an expanded access protocol and safety database for NRX-101's study in treatment-resistant bipolar depression with risk of self-harm.

我們對 NRX-101 潛在的救生作用感到非常興奮。為了支持這些項目的持續臨床開發，我們宣布完成 290 萬美元的註冊直接發行，以支持我們的管道工作，更具體地說，啟動 NRX-101 研究的擴展訪問協議和安全數據庫具有自殘風險的難治性雙相抑鬱症。

This database allows us to investigate the expanded indication put forward by the FDA's psychiatric division in our Type B meeting for our registrational trial. And we look forward to providing you all with an update of our clinical activity in the months to come.

該數據庫使我們能夠調查 FDA 精神科部門在我們的註冊試驗 B 類會議上提出的擴展適應症。我們期待在未來幾個月為大家提供我們臨床活動的最新信息。

The continued financial support from our existing shareholders, based on our existing data and ongoing trials, demonstrates their commitment to people living with serious CNS disorders and the potential of NRX-101 to become commercially successful.

基於我們現有的數據和正在進行的試驗，我們現有股東的持續財政支持表明了他們對患有嚴重中樞神經系統疾病的患者的承諾以及 NRX-101 取得商業成功的潛力。

We have achieved the number of significant corporate milestones in recent months. In February, we received notice of the issuance of the US patent for NRX-101, which covers the use of NRX-101 to treat patients suffering from depression, including bipolar depression or major depression with or without suicidality. This patent strengthens the company's intellectual property position until at least 2033.

近幾個月來，我們實現了許多重要的企業里程碑。今年 2 月，我們收到了 NRX-101 獲得美國專利的通知，該專利涵蓋使用 NRX-101 治療抑鬱症患者，包括雙相抑鬱症或伴有或不伴有自殺傾向的重度抑鬱症。該專利至少在 2033 年之前加強了公司的知識產權地位。

We also strengthened our deep bench of healthcare executives and world-class psychiatrists in recent months. We announced the appointment of Professor Andrew Nierenberg and Professor Marion Leboyer to our Advisory Board in March. Professor Nierenberg is a Chair, Professor of Psychiatry at Harvard Medical School, and is the Director of the Dauten Family Center for Bipolar Research at Massachusetts General Hospital. He is one of the world's most published scientists in the area of psychiatric research, particularly as it relates to bipolar disease. We are honored to have him as principal investigator of our ongoing clinical trial in suicidal bipolar depression.

近幾個月來，我們還加強了醫療保健高管和世界級精神科醫生的陣容。我們於三月份宣布任命 Andrew Nierenberg 教授和 Marion Leboyer 教授為我們的顧問委員會成員。 Nierenberg 教授是哈佛醫學院精神病學系主任、教授，也是馬薩諸塞州總醫院 Dauten 家庭雙相情感障礙研究中心主任。他是世界上精神病學研究領域發表論文最多的科學家之一，特別是與雙相情感障礙相關的研究。我們很榮幸邀請他作為我們正在進行的自殺性雙相抑鬱症臨床試驗的首席研究員。

Professor Leboyer is one of France's leading psychiatrist, an extensively published researcher in the field of neuropsychiatry, particularly as it relates to bipolar disease and autism. In addition to her academic achievements, Professor Leboyer chairs the Fondation FondaMental and has facilitated an important collaboration between NRX and French psychiatry researchers, studying ketamine for the treatment of acute suicidality among hospitalized patients, particularly patients with bipolar depression. Please see their biographies on our website.

勒博耶教授是法國頂尖的精神病學家之一，也是神經精神病學領域發表了大量論文的研究人員，特別是在雙相情感障礙和自閉症方面。除了學術成就外，Leboyer 教授還擔任 FondaMental 基金會主席，並促進了 NRX 和法國精神病學研究人員之間的重要合作，研究氯胺酮用於治療住院患者（尤其是雙相抑鬱症患者）的急性自殺傾向。請在我們的網站上查看他們的傳記。

Also, the company has continued to engage in a strategic conversation focused on funding the drug approval and commercialization of our products. In parallel, the company has established an ongoing dialogue with Streeterville Capital LLC, the company's current debt lender, to address the company's current debt facility to best support the ongoing needs of the clinical trial.

此外，該公司繼續進行戰略對話，重點是為我們產品的藥物審批和商業化提供資金。與此同時，該公司已與該公司當前的債務貸款人 Streeterville Capital LLC 建立了持續對話，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。

We are confident that we have achieved a strong foundation for NRX that enables us to efficiently advance our clinical trials and make a difference in the lives of patients with life-threatening psychiatric disorders.

我們相信，我們已經為 NRX 奠定了堅實的基礎，使我們能夠有效地推進我們的臨床試驗，並改變患有危及生命的精神疾病患者的生活。

I would like to express my gratitude to the patients, the NRX team, clinical trial investigators, and shareholders for their continued support.

我謹向患者、NRX 團隊、臨床試驗研究者和股東的持續支持表示感謝。

With that, I'll turn it over to Seth for a brief overview of our financial results.

接下來，我將把它交給 Seth，讓他簡要概述我們的財務業績。

Good morning, everyone. Thank you, Stephen. I will now review the highlights for first quarter 2023 financial results.

大家，早安。謝謝你，斯蒂芬。我現在將回顧 2023 年第一季度財務業績的要點。

For the three months ended March 31, 2023, NRX Pharmaceuticals recorded $3.7 million of R&D expenses compared to $5.5 million for the quarter ended March 31, 2022. The decrease of $1.8 million is related primarily to a reduction in clinical trials and development expense related to our discontinued activities related to ZYESAMI.

截至 2023 年 3 月 31 日的三個月，NRX Pharmaceuticals 的研發費用為 370 萬美元，而截至 2022 年 3 月 31 日的季度為 550 萬美元。減少 180 萬美元主要與臨床試驗和開發費用的減少有關我們已停止與 ZYESAMI 相關的活動。

For the three months ended March 31, 2023, NRX Pharmaceuticals recorded $5.8 million of G&A expenses compared to $10.2 million for the three months ended March 31, 2022. The decrease of $4.4 million was primarily related to a decrease in legal, professional and accounting fees.

截至 2023 年 3 月 31 日止的三個月，NRX Pharmaceuticals 的一般管理費用為 580 萬美元，而截至 2022 年 3 月 31 日止的三個月為 1,020 萬美元。減少 440 萬美元主要與法律、專業和會計費用的減少有關。

Our net loss for the quarter was $11 million, an improvement of $2.4 million compared to the net loss of $13.4 million for the comparable quarter in 2022.

我們本季度的淨虧損為 1100 萬美元，比 2022 年同期淨虧損 1340 萬美元減少了 240 萬美元。

On the financial side, our cash resources were enhanced in March when we entered into a securities purchase agreement with accredited investors who had previously established positions in the company. This transaction involved the sale of approximately 3.9 million shares of the company's common stock and a five-year warrant in a registered direct offering priced slightly above the market at $0.75 per unit for the securities.

在財務方面，我們的現金資源在三月份得到了增強，當時我們與先前在該公司建立頭寸的合格投資者簽訂了證券購買協議。此次交易涉及出售約 390 萬股公司普通股以及註冊直接發行的五年期認股權證，證券價格略高於市場價格，每單位 0.75 美元。

The investors agreed not to sell these shares of common stock or exercise the warrants for six months following the issuance date. The aggregate gross proceeds from -- to the company for the offering was approximately $2.9 million.

投資者同意在發行日後六個月內不出售這些普通股或行使認股權證。該公司此次發行的總收益約為 290 萬美元。

As of March 31, 2023, we had approximately $16.5 million in cash. Assuming future debt payments can continue to be made in stock, the $16.5 million of cash and cash equivalents at the end of the first quarter of 2023 is expected to fund the company's operations through the expected delivery of data in the fourth quarter of this year from our Phase 2b/3 trial.

截至 2023 年 3 月 31 日，我們擁有約 1650 萬美元現金。假設未來債務支付可以繼續以庫存方式支付，預計到 2023 年第一季度末的 1650 萬美元現金和現金等價物將通過今年第四季度預計交付的數據為公司的運營提供資金。我們的 2b/3 期試驗。

Additionally, we are evaluating operation efficiencies associated with the completion of our manufacturing activities as well as considering capital raising activities to extend this runway.

此外，我們正在評估與完成製造活動相關的運營效率，並考慮融資活動來擴展這條跑道。

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. The past quarter has been incredibly productive. And we look forward to advancing our NRX-101 program in suicidal bipolar depression, PTSD, and chronic pain in the months to come. Based on the experience we have as a clinical trial company working in CNS, NRX is uniquely positioned for success in future growth.

謝謝，塞思。過去的一個季度非常富有成效。我們期待在未來幾個月內推進我們的 NRX-101 項目在自殺性雙相抑鬱症、創傷後應激障礙 (PTSD) 和慢性疼痛方面的進展。根據我們作為中樞神經系統臨床試驗公司的經驗，NRX 擁有獨特的優勢，能夠在未來的發展中取得成功。

We plan to build on a momentum in the remainder of 2023 as we continue to execute on multiple regulatory and clinical catalysts. We believe that NRX-101 is a potentially life-saving medicine that could change the treatment paradigm for life-threatening psychiatric conditions which is the driving force behind our mission to meeting the needs of underserved patients with serious CNS disorders.

我們計劃在 2023 年剩餘時間內繼續保持勢頭，繼續執行多種監管和臨床催化劑。我們相信 NRX-101 是一種潛在的挽救生命的藥物，可以改變危及生命的精神疾病的治療模式，這是我們滿足服務不足的嚴重中樞神經系統疾病患者需求的驅動力。

We look forward to updating you on the near-term milestones, which are on-track for the coming year, including the initiation of our study of NRX-101 and PTSD, the advancement of NRX-101 in chronic pain associated with depression, as well as future updates on breakthrough therapy designation meeting for NRX-101 in treatment-resistant suicidal bipolar depression, as well as data from our Phase 2b/3 study in the fourth quarter.

我們期待向您通報來年有望實現的近期里程碑的最新進展，包括啟動 NRX-101 和 PTSD 的研究、NRX-101 在與抑鬱相關的慢性疼痛方面的進展，以及以及 NRX-101 治療難治性自殺性雙相抑鬱症突破性療法指定會議的未來更新，以及我們第四季度 2b/3 期研究的數據。

With the shared commitment of our investors, our team, and our researchers, we aim to bring hope to the millions of patients with suicidal bipolar depression and PTSD who have been systematically excluded from trials of previous antidepressants.

在我們的投資者、我們的團隊和研究人員的共同承諾下，我們的目標是為數百萬患有自殺性雙相抑鬱症和創傷後應激障礙的患者帶來希望，他們被系統地排除在先前的抗抑鬱藥試驗之外。

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

接線員，我們已準備好回答電話中的問題。

All right then. We will begin the question-and-answer session. (Operator Instructions)

那好吧。我們將開始問答環節。 （操作員說明）

Ed Woo, Ascendiant Capital.

艾德·吳，Ascendian Capital。

Yes. Thank you for taking my question. My question is on PTSD additional indication. Do you anticipate starting filing the IND this quarter or the next quarter in order to start a trial by the fourth quarter?

是的。感謝您回答我的問題。我的問題是關於創傷後應激障礙（PTSD）的額外指示。您預計本季度或下季度開始提交 IND 申請，以便在第四季度開始試驗嗎？

Thank you, Ed. This is Jonathan Javitt. Yes, we do anticipate filing that IND.

謝謝你，艾德。這是喬納森·賈維特。是的，我們確實預計會提交 IND。

Great. And then in terms of how large the possible trial can be, do you have any indications of how big it may be?

偉大的。那麼就可能的試驗規模而言，您是否有任何跡象表明它可能有多大？

Well, I think from a registration perspective, there were some precedents from the anti-depressant recent approvals. But until there's a formal meeting with FDA, it's not possible to know exactly what the sample size would be. But I think there's some good precedence in recent approvals of anti-depressants.

嗯，我認為從註冊的角度來看，最近抗抑鬱藥的批准有一些先例。但在與 FDA 舉行正式會議之前，不可能確切知道樣本量是多少。但我認為最近抗抑鬱藥的批准有一些良好的先例。

Great. And then my last question is: in terms of what you guys have learned with your current study, do you think that you'll be able to use any of that data in order facilitate the trial possibly being easier or being able to go faster?

偉大的。然後我的最後一個問題是：就你們目前的研究中學到的東西而言，你們認為你們能夠使用這些數據來促進試驗變得更容易或能夠進行得更快嗎？

Well, certainly, a trial for any indication adds to the safety database for all indications, and clinical experience with a drug is always helpful. But the endpoints in PTSD are a little different than the endpoints in depression. Because in PTSD, you're primarily relying on the CAPS-5 scale looking at symptoms of flashbacks and recurring memory -- sorry, recurring fear memory.

當然，任何適應症的試驗都會增加所有適應症的安全數據庫，並且藥物的臨床經驗總是有幫助的。但 PTSD 的終點與抑鬱症的終點略有不同。因為在 PTSD 中，你主要依靠 CAPS-5 量表來觀察閃回和重複記憶的症狀——抱歉，是重複出現的恐懼記憶。

Some of that's been demonstrated with ketamine, which as you know is a very potent NMDA antagonist. So there's reason to be optimistic that a more controllable NMDA antagonist might also relieve symptoms of PTSD.

其中一些已通過氯胺酮得到證實，如您所知，氯胺酮是一種非常有效的 NMDA 拮抗劑。因此，我們有理由樂觀地認為，更可控的 NMDA 拮抗劑也可能緩解 PTSD 症狀。

Great. Well, thanks for giving me the answer, and I wish you guys good luck. Thank you.

偉大的。嗯，謝謝你給我答案，祝你們好運。謝謝。

Thank you, Ed.

謝謝你，艾德。

(Operator Instructions)

（操作員說明）

Jason Kolbert, Dawson James.

傑森·科爾伯特，道森·詹姆斯。

Hi, guys. Congratulations on the progress.

嗨，大家好。祝賀取得的進展。

Good morning, Jason. Thank you.

早上好，傑森。謝謝。

Good morning. Can you talk a little bit about the dynamics of actually enrolling these bipolar depressed patients with suicide ideology? How do they come to you? How do they end up being referred into the trial? What's the entry criteria on these patients? And then I want to talk a little bit about what are the endpoints of the trial.

早上好。您能談談實際招募這些具有自殺意識形態的雙相抑鬱患者的動態嗎？他們怎麼來找你？他們最終如何被轉介參加審判？這些患者的進入標準是什麼？然後我想談談試驗的終點是什麼。

Thank you, Jason. As you know, we put the protocol for the trial on to www.clinicaltrials.gov, so people are free to read it. And the trial enrolls patients who have severe depression as measured by a score of 30 or higher on the MADRS scale and also have suicidal ideation to the extent that they have a score of 3 or higher on the Columbia Suicide Severity Rating Scale.

謝謝你，傑森。如您所知，我們將試驗方案放在 www.clinicaltrials.gov 上，以便人們可以自由閱讀。該試驗招募的患者患有嚴重抑鬱症（MADRS 量表得分為 30 或更高），並且有自殺意念（哥倫比亞自殺嚴重程度評定量表得分為 3 或更高）。

So historically, we've relied on traditional study sites to recruit these patients either from the patients that they already know in their clinical treatment programs or patients that they're able to reach out to in the community.

因此，從歷史上看，我們一直依靠傳統的研究場所來招募這些患者，要么是他們在臨床治療計劃中已經認識的患者，要么是他們能夠在社區中接觸到的患者。

As Steve discussed earlier in the call, we've decided to go broader than that. And we've engaged 1nHealth really to stand up a recruitment effort that's licensed in 45 states so far, in conjunction with a decentralized clinical trials organization called Science 37. Such that we're able to recruit patients in most of the country. And we're in the process of reaching out to a very large pool of people who've identified themselves as having bipolar depression.

正如史蒂夫早些時候在電話會議中討論的那樣，我們決定擴大範圍。我們已經與 1nHealth 合作，與一家名為 Science 37 的分散臨床試驗組織合作，開展招募工作，迄今為止已在 45 個州獲得許可。這樣我們就能夠在全國大部分地區招募患者。我們正在接觸一大批自認為患有雙相抑鬱症的人。

And rather than demand that those patients come to a study site that could be some distance away from them, we have teams of nurses who are able to go do the initial screening at a location convenient to the potential participant, including their home, to draw blood as needed by the protocol, again, at their location, And then we have psychometric raters who are able to do the assessments associated with the primary and secondary endpoints for the study on a remote basis.

我們並沒有要求這些患者來到離他們有一定距離的研究地點，而是有護士團隊，他們能夠在潛在參與者方便的地方（包括他們的家）進行初步篩查，以進行初步篩查。再次按照方案的需要，在他們的所在地進行血液，然後我們有心理測量評估員，他們能夠遠程進行與研究的主要和次要終點相關的評估。

And we anticipate that by opening up our recruitment in that manner, we can much more efficiently recruit patients into the study, make it easier for them to stay in the study, and at the same time, be able to control the quality of the data through a very small pool of very highly experienced raters.

我們預計，通過以這種方式開放招募，我們可以更有效地招募患者參與研究，使他們更容易留在研究中，同時能夠控制數據的質量通過一小群經驗豐富的評估者進行評估。

Yeah. I mean, I can appreciate the infrastructure required to accomplish all of that. And given where you are, how confident are you in the velocity of enrollment that supports that statement that you're funded through kind of the data read at the end of the year?

是的。我的意思是，我很欣賞完成所有這些所需的基礎設施。考慮到您所處的位置，您對支持您通過年底讀取的數據獲得資助的聲明的註冊速度有多大信心？

Well, prediction is challenging, especially as Yogi Berra once said, when you're talking about the future. What we can tell you is that in the first week of the 1nHealth initiative, there were 150 inbound inquiries of which 75 were patients who were deemed to potentially meet the study criteria.

好吧，預測是具有挑戰性的，尤其是正如 Yogi Berra 曾經說過的，當你談論未來時。我們可以告訴您的是，在 1nHealth 計劃實施的第一周，有 150 起入站詢問，其中 75 名患者被認為可能符合研究標準。

So the interest in this study is very palpable. And by the time we speak again, I think we'll have a very good handle on the velocity with which enrolment can be achieved.

因此，人們對這項研究的興趣是非常明顯的。當我們再次發言時，我認為我們將很好地掌握實現註冊的速度。

Okay. Thank you. And can you break down for me -- just review with me the primary endpoint and what exactly the components of it are that are measured?

好的。謝謝。您能否幫我分析一下——與我一起回顧一下主要終點以及測量的具體組成部分是什麼？

So the primary endpoint is very clear cut. It's the same primary endpoint that was used to approve lurasidone. It's the same primary endpoint that was used to approve [Abilify], which is change in the MADRS and depression score, the Montgomery-Asberg Depression Rating Scale, over 42 days using what's called a mixed model repeated measures regression. All of that's described in detail in our protocol, which people are free to read.

所以主要終點非常明確。這與批准魯拉西酮的主要終點相同。這與批准 [Abilify] 所使用的主要終點相同，即 MADRS 和抑鬱評分（蒙哥馬利-阿斯伯格抑鬱評定量表）在 42 天內使用所謂的混合模型重複測量回歸的變化。所有這些都在我們的協議中進行了詳細描述，人們可以免費閱讀。

And the secondary endpoint, the key secondaries are measurement, what time to treatment failure? In other words, how long is it between the time you start the study and the time that the treating physicians determine that the medicine you were randomized to isn't working? That's one secondary endpoint.

次要終點，關鍵的次要是測量，什麼時候治療失敗？換句話說，從您開始研究到治療醫生確定您隨機服用的藥物無效，需要多長時間？這是一個次要終點。

And the other secondary endpoint is change on the Clinical Global Impression Suicides Severity Scale, which is a scale that we saw significant change on -- in the STABIL-B study, in the Phase 2 studies that are in this breakthrough therapy designation. So the endpoints are quite transparent in that regard.

另一個次要終點是臨床總體印象自殺嚴重程度量表的變化，我們在 STABIL-B 研究和屬於這一突破性治療指定的 2 期研究中看到了顯著變化。因此，端點在這方面是相當透明的。

Really appreciate the update. Thank you. We'll be watching the progress.

真的很感謝更新。謝謝。我們將關注進展。

Thank you.

謝謝。

As we have no further questions, this concludes our question-and-answer session.

由於我們沒有其他問題，我們的問答環節到此結束。

I would like to turn the conference back over to Suzanne for any closing remarks.

我想將會議轉回給蘇珊，讓她發表閉幕詞。

Thank you, everyone. That is all the time we have for questions. Thank you for joining us this morning. This concludes the NRX Pharmaceuticals' first-quarter 2023 financial results conference call. Have a great day.

謝謝大家。這就是我們提問的全部時間。感謝您今天早上加入我們。 NRX Pharmaceuticals 2023 年第一季度財務業績電話會議至此結束。祝你有美好的一天。

The conference is now concluded. Thank you for your participation. You may now disconnect.

會議現已結束。感謝您的參與。您現在可以斷開連接。