NRX Pharmaceuticals Inc (NRXP) 2022 Q3 法說會逐字稿

Good morning, and welcome to the NRx Pharmaceuticals Third Quarter 2022 Earnings Conference Call. All participants will be in listen-only mode. (Operator Instructions) After today's presentation, there will be an opportunity to ask questions. (Operator Instructions) Please note this event is being recorded. I would now like to turn the conference over to Suzanne Messere with Stern Investor Relations. Please, go ahead.

早安，歡迎參加 NRx Pharmaceuticals 2022 年第三季財報電話會議。所有參與者將處於僅聽模式。 （操作員說明）今天的演示結束後，將有機會提問。 （操作員說明）請注意此事件正在被記錄。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, Andrea. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under U.S. 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，安德里亞。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's speak only as 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-Q being filing today as well, which maybe accessed from the investor's page of the NRx Pharmaceuticals website.

本次電話會議期間所做的前瞻性陳述僅以本新聞稿發布之日為準。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今天稍早發布的新聞稿中以及該公司今天提交的 10-Q 表格中，可以從 NRx Pharmaceuticals 網站的投資者頁面存取該表格。

Joining me on today's call 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 the review of the company's financial results, and then Stephen will review upcoming milestones before making closing comments and opening up for questions.

參加今天 NRx Pharmaceuticals 電話會議的還有執行長 Stephen Willard 和財務長兼財務主管 Seth Van Voorhees。史蒂芬將提供公司進展的總結；塞斯將審查公司的財務業績，然後史蒂芬將審查即將到來的里程碑，然後做出總結評論並提出問題。

During the Q&A session, Stephen and Seth will be joined Robert Besthof, Head of Operations and Chief Commercial Officer; and Jonathan Javitt, the Company's Chief Scientific Officer to address investor questions. I will now turn the call over to Stephen.

在問答環節中，Stephen 和 Seth 將與營運主管兼首席商務官 Robert Besthof 一起參加；公司首席科學官喬納森·賈維特 (Jonathan Javitt) 回答了投資者的問題。我現在將把電話轉給史蒂芬。

Thank you, Suzanne. Good morning, everyone, and thank you for joining us. Today we will discuss the third quarter results for our company and provide a business update. In March, we announced that our primary strategic focus going forward is on our psychiatry franchise and the late-stage development of NRX-101, our lead investigational compound.

謝謝你，蘇珊娜。大家早安，感謝您加入我們。今天我們將討論我們公司第三季的業績並提供業務更新。今年 3 月，我們宣布未來的主要策略重點是我們的精神病學特許經營權和我們的主要研究化合物 NRX-101 的後期開發。

Today, we estimate the U.S. annual peak sales potential for bipolar depression with suicidality to be around $2 billion. There are only five drugs currently approved for bipolar depression, none of which is indicated for patients with suicidality. In fact, such patients were excluded from their clinical trials.

如今，我們估計美國患有自殺傾向的雙相憂鬱症的年高峰銷售潛力約為 20 億美元。目前只有五種藥物被批准用於治療雙相憂鬱症，其中沒有一種藥物適用於有自殺傾向的患者。事實上，此類患者被排除在臨床試驗之外。

Our Phase 2 study specifically enrolled patients with high levels of suicide risk and showed that NRX-101 has the potential to provide improved clinical outcomes in such patients, who is only currently approved therapeutical alternative is electroshock therapy. That is why the FDA gave us breakthrough therapy designation and a special protocol agreement allowing for registrational study with 72 patients.

我們的 2 期研究專門招募了自殺風險較高的患者，並表明 NRX-101 有潛力為此類患者提供改善的臨床結果，而目前唯一批准的治療替代方案是電擊療法。這就是為什麼 FDA 給予我們突破性治療指定和特殊協議協議，允許對 72 名患者進行註冊研究。

In recent months, we have made substantial progress in advancing our development of NRX-101 for the treatment of bipolar depression with suicidality and PTSD, while also exploring other psychiatric indications. In March, we announced the strategic decision to initiate our Phase 3 trial following the release of NRX-101 using processes suitable for ultimate commercial sale of our medicine should we demonstrate safety and efficacy. That milestone was completed and announced last week.

近幾個月來，我們在推進NRX-101 的開發方面取得了實質性進展，該NRX-101 用於治療伴有自殺傾向的雙相抑鬱症和創傷後應激障礙(PTSD)，同時還在探索其他精神科適應症。今年 3 月，我們宣布了一項戰略決定，即在 NRX-101 發布後啟動我們的 3 期試驗，如果我們證明安全性和有效性，則使用適合我們藥物最終商業銷售的流程。這一里程碑已於上週完成並宣布。

Thus, we anticipate initiating our Phase 3 trial under the FDA special protocol agreement in 72 patients as pre-specified with the FDA by the end of this year. We expect to report top line data in the second half of 2023 with initiation of a potential NDA submission by year-end 2023, assuming efficacy and safety has been met.

因此，我們預計在今年年底之前根據 FDA 的特別協議協議在 72 名患者中啟動我們的 3 期試驗。假設功效和安全性已得到滿足，我們預計將在 2023 年下半年報告頂線數據，並在 2023 年底前啟動潛在的 NDA 提交。

Last week, we also announced a debt financing that we project provide this with adequate capital to support this Phase 3 program. NRX-101 is a fixed dose combination of d D-cycloserine, an NMDA-receptor modulator and lurasidone, the drug commonly used for bipolar disorder. To our knowledge, NRX-101 is the only oral antidepressant either approved or in development that targets patients with bipolar depression and active suicidality, which typically is an exclusion criteria in clinical studies of depression in PTSD.

上週，我們還宣布了一項債務融資，我們預計將為該專案提供足夠的資金來支持第三階段計劃。 NRX-101 是 d-D-環絲胺酸（一種 NMDA 受體調節劑）和魯拉西酮（常用於治療躁鬱症的藥物）的固定劑量組合。據我們所知，NRX-101 是唯一一種已批准或正在開發的口服抗憂鬱藥，針對雙相憂鬱症和主動自殺患者，這通常是 PTSD 憂鬱症臨床研究的排除標準。

The tragic reality of bipolar depression is that if you know two people with this condition, the odds are that one will attempt suicide. And if you know five people with this condition, the odds are that one will die from suicide.

躁鬱症的悲慘現實是，如果你認識兩個患有這種疾病的人，那麼其中一個很可能會嘗試自殺。如果你認識五個患有這種疾病的人，那麼其中一個很可能會死於自殺。

Our Phase 2 and non-clinical evidence suggests that NRX-101 may achieve many of the therapeutic benefits seen with ketamine, which is increasingly used to treat patients with depression and suicidality. Ketamine is known to induce [hallucinogens]. Ketamine is also well known to be neurotoxic, ensuring to kill brain cells in both animal models and in human and clinical reports.

我們的第 2 期和非臨床證據表明，NRX-101 可以實現氯胺酮的許多治療益處，氯胺酮越來越多地用於治療憂鬱症和自殺患者。已知氯胺酮會誘發[致幻劑​​]。眾所周知，氯胺酮具有神經毒性，在動物模型以及人類和臨床報告中都能殺死腦細胞。

FCA has issued warnings about repeated use of ketamine and anesthesia for this reason. We have demonstrated that the ingredients of NRX-101 had not shown potential generic toxicity even at 10 times the expected deaths. We have released preclinical findings demonstrating that unlike ketamine, the NMDA component in NRX-101 is non-addictive.

為此，FCA 對重複使用氯胺酮和麻醉發出了警告。我們已經證明，即使是預期死亡人數的 10 倍，NRX-101 的成分也沒有表現出潛在的一般毒性。我們發布的臨床前研究結果表明，與氯胺酮不同，NRX-101 中的 NMDA 成分不會成癮。

Our stage would be Phase 2 proof-of-concept study showed a statistically significant reduction in both depression and suicidality, compared to standard therapy in patients with bipolar depression, who were acutely suicidal and who were initially stabilized the academy.

我們的第二階段概念驗證研究顯示，與雙相憂鬱症患者的標準治療相比，憂鬱症和自殺率在統計上顯著降低，這些患者有嚴重的自殺傾向，並且最初在學院穩定下來。

To our knowledge, no oral drug therapy has ever been able to demonstrate a reduction in both depression and suicidal tendencies in this patient population. This is clinically relevant because antidepressants carry black box warning labels regarding potential for increased risk of suicide in vulnerable populations.

據我們所知，沒有任何口服藥物療法能夠證明該患者族群的憂鬱症和自殺傾向均降低。這具有臨床相關性，因為抗憂鬱藥物帶有黑框警告標籤，提示弱勢群體自殺風險可能增加。

Based on NRX-101 differentiated therapeutic profile, we believe that we have the potential to address a significant unmet medical need for patients, who are currently underserved by available treatment options. Please see our press release today issued earlier for our NRX-101 clinical and regulatory milestones achieved to-date.

基於 NRX-101 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未滿足的重大醫療需求。請參閱我們今天早些時候發布的新聞稿，以了解我們迄今為止所實現的 NRX-101 臨床和監管里程碑。

This previous milestone established a strong foundation that enables us to embark on a highly efficient registrational Phase 3 program with FDA's advanced commitment to accept the regulatory finding from us. Should we successfully determine safety and efficacy and demonstrate the truth. This foundation also allows us to significantly expand the addressable population of patients with bipolar depression and sub-acute suicidality to patients, who are treated in an outpatient setting enter those with PTSD.

先前的這一里程碑奠定了堅實的基礎，使我們能夠開展高效的註冊第 3 階段計劃，FDA 已提前承諾接受我們的監管調查結果。我們是否應該成功地確定安全性和有效性並證明真相。這項基礎也使我們能夠將雙相憂鬱症和亞急性自殺患者的可尋址人群顯著擴大到在門診接受治療的患者和創傷後壓力症候群患者。

Now I would like to cover some of our achievements in the third quarter. We are on track to report top line clinical data for our ongoing Phase 2 clinical trial of NRX-101 in patients with bipolar depression and sub-acute suicidal ideation in the first quarter of 2023. The objective of the double-blind study is to demonstrate NRX-101's ability to significantly improve both depression and suicidality over six weeks when taken twice daily.

現在我想介紹一下我們第三季所取得的一些成就。我們預計在 2023 年第一季報告我們正在進行的 NRX-101 2 期臨床試驗的主要臨床數據，該試驗針對雙相憂鬱症和亞急性自殺意念患者。雙盲研究的目的是證明每天服用兩次，NRX-101 在六週內能夠顯著改善憂鬱症和自殺傾向。

The study involves patients with bipolar depression and sub-acute suicidality and does not require the use of ketamine. As mentioned previously, this is one of the studies that could enable us to expand the potential indication for NRX-101, as well as offer a more convenient treatment option on an outpatient setting. We are also on track with plans to initiate registrational Phase 3 clinical trial of NRX-101 by year-end in patients with severe bipolar depression and acute suicidal ideation. This trial will be randomized double-blind trial of NRX-101 versus lurasidone alone in 72 patients.

該研究涉及雙相憂鬱症和亞急性自殺患者，不需要使用氯胺酮。如前所述，這是一項研究，可以使我們擴大 NRX-101 的潛在適應症，並在門診環境中提供更方便的治療選擇。我們也計劃在年底前針對嚴重雙相憂鬱症和急性自殺意念患者啟動 NRX-101 的註冊 3 期臨床試驗。該試驗將在 72 名患者中進行 NRX-101 與單獨魯拉西酮的隨機雙盲試驗。

We expect to confirm our Phase 2 trial findings following a successful response to a single infusion of ketamine, treatment with NRX-101 would be superior to lurasidone, the current standard-of-care in the patient population. We will do this by showing improvement in symptoms of depression as measured by the Montgomery and Asberg Depression Rating Scale. Because of the acute nature of these patients, we agreed with the FDA to compare our drug to lurasidone, a standard-of-care medication rather than to placebo and successful this will provide clear commercial differentiation.

我們希望在單次注射氯胺酮成功緩解後確認我們的 2 期試驗結果，NRX-101 治療將優於魯拉西酮（目前患者群體的護理標準）。我們將透過蒙哥馬利和亞斯伯格症評定量表測量憂鬱症狀的改善來做到這一點。由於這些患者的急性性質，我們同意 FDA 將我們的藥物與魯拉西酮（一種標準治療藥物）而不是安慰劑進行比較，如果成功，這將提供明顯的商業差異化。

In September, we announced plans for an additional indication in PTSD approximately 9 million individuals in our country experienced PTSD, one-third of the room at severe PTSD, between 17 million and 22 million is our (inaudible) are back in the last every day to suicide.

9 月，我們宣布了針對PTSD 的額外適應症的計劃，我國約有900 萬人經歷過PTSD，三分之一的人患有嚴重PTSD，我們（聽不清楚）每天有1700 萬到2200 萬之間的人回來自殺。

We view this as another area of very high unmet medical need. We expect that our medicine will show antidepressant effects in PTSD. However, we are also hopeful that our medicine will demonstrate specific effects on the peer memory components of PTSD and directly reduce symptoms of PTSD beyond depression. Today, there is no approved medicine for these specific PTSD symptoms and our preclinical studies have shown reduction in fear memory associated with D-cycloserine.

我們認為這是醫療需求未被滿足的另一個領域。我們期望我們的藥物能夠在創傷後壓力症候群（PTSD）中顯示出抗憂鬱作用。然而，我們也希望我們的藥物能對 PTSD 的同儕記憶成分產生特定的效果，並直接減輕憂鬱症以外的 PTSD 症狀。如今，還沒有批准的藥物可以治療這些特定的 PTSD 症狀，我們的臨床前研究表明，D-環絲氨酸可以減少恐懼記憶。

As announced last week, we submitted our expected commercial stage manufacturing process to the FDA, so that we can include this drug product in our upcoming registrational Phase 3 trial. We're excited about this milestone in particular, as we believe that adopting a commercial ready manufacturing process now could lead to a more seamless NDA submission, review and approval process with net -- without the need [to begin] studies.

正如上周宣布的那樣，我們向 FDA 提交了預期的商業階段生產工藝，以便我們可以將該藥品納入即將進行的註冊 3 期試驗。我們對這一里程碑尤其感到興奮，因為我們相信，現在採用商業化的製造流程可以帶來更無縫的 NDA 提交、審查和批准流程，而無需[開始]研究。

Yesterday, we announced with Relief Therapeutics Holding that we have entered into a definitive settlement agreement to resolve pending litigation at closing to be held within the next 30-days. More details on the settlement terms will be found in the unit release published on November 13, 2022 and will be in a future 8-K filing with the SEC upon settlement.

昨天，我們宣布與 Relief Therapeutics Holding 達成最終和解協議，以在未來 30 天內解決懸而未決的訴訟。有關和解條款的更多詳細資訊將在 2022 年 11 月 13 日發布的單位新聞稿中找到，並將在和解後向 SEC 提交的 8-K 文件中找到。

We believe that this settlement is in our shareholder's interest for the following reasons: we have committed to focusing on our core CNS franchise and a book-to-bill is not part of that franchise. The institutional investors, who have capitalized our company and the analysts, who evaluate our company advise us to focus on our CNS franchise.

我們認為，這項和解符合我們股東的利益，原因如下：我們致力於專注於我們的核心 CNS 特許經營權，而訂單到帳單業務不屬於該特許經營權的一部分。為我們公司提供資本的機構投資者和評估我們公司的分析師建議我們專注於 CNS 特許經營權。

Under the terms of the settlement Relief is committed to all further costs of the risk to build development, while paying us up to $43 million in milestones and royalties should they succeed. The failure of the -- of book-to-bill in both the NIH and BARDA trial indicates limited potential for (inaudible) in widespread use. So it's a deal that I think is a real benefit for NRX shareholder.

根據和解條款，Relief 承諾承擔建設開發風險的所有進一步費用，同時如果開發成功，將向我們支付高達 4,300 萬美元的里程碑費用和特許權使用費。 NIH 和 BARDA 試驗中「從訂單到帳單」的失敗表明（聽不清楚）廣泛使用的潛力有限。因此，我認為這筆交易對 NRX 股東來說是真正有利的。

Finally, we announced debt financing with net proceeds to $10 million on November 7, 2022, that is expected to support our clinical development activities for NRX-101. With that, I will turn it over to Seth for a brief overview of our financial results. Seth?

最後，我們在 2022 年 11 月 7 日宣布進行債務融資，淨收益達到 1,000 萬美元，預計將支持我們的 NRX-101 臨床開發活動。接下來，我將把它交給賽斯，讓他簡要概述我們的財務表現。賽斯？

Thank you, Stephen, and good morning, everyone. It's a pleasure to speak with you again today. And I would now like to review the highlights of our third financial results.

謝謝你，史蒂芬，大家早安。很高興今天再次與您交談。現在我想回顧一下我們第三次財務表現的亮點。

For the three month period ended September 30, 2022 R&D expenses totaled $4.1 million, compared to $6.3 million for the same period in 2021. The decrease in R&D expenses related primarily to a decrease in clinical trials and development expenses related to ZYESAMI. As announced in March of this year, we are focusing most of our R&D expenditures on our psychiatry franchise going forward.

截至2022年9月30日的三個月期間，研發費用總計為410萬美元，而2021年同期為630萬美元。研發費用的減少主要與ZYESAMI相關的臨床試驗和開發費用的減少有關。正如今年 3 月宣布的那樣，我們將把大部分研發支出集中在我們的精神病學特許經營權上。

For the nine month period ended September 30, 2022, R&D expenses totaled $12.6 million, as compared to $13.8 million for the same period in 2021. The net increase of $1.3 million is related to a decrease of $1.5 million in clinical trials and development expenses related to ZYESAMI, a decrease of $0.5 million in fees paid to regulatory and process development consultants, partially offset by an increase of $0.7 million in regulatory and process development costs.

截至 2022 年 9 月 30 日的九個月期間，研發費用總計 1,260 萬美元，而 2021 年同期為 1,380 萬美元。淨增加 130 萬美元與臨床試驗和相關開發費用減少 150 萬美元有關。向ZYESAMI 支付。的監管和工藝開發顧問費用減少了50 萬美元，但被監管和製程開發成本增加了70 萬美元部分抵銷。

The nine month period includes R&D costs related to both to ZYESAMI and to COVID vaccine development, costs that we do not anticipate to incur going forward.

這九個月的期限包括與 ZYESAMI 和新冠疫苗開發相關的研發成本，我們預期未來不會產生這些成本。

For the three month period ended September 30, 2022, G&A expenses totaled $5.0 million, compared to $13.8 million for the same period in 2021. The decrease from G&A expenses was partially related to a reduction in consulting fees in 2022.

截至 2022 年 9 月 30 日的三個月期間，一般及行政費用總計 500 萬美元，而 2021 年同期為 1,380 萬美元。一般及行政費用的減少部分與 2022 年諮詢費的減少有關。

For the nine month period ended September 30, 2022, G&A expenses totaled $21.9 million, as compared to $28.4 million for the same period in 2021. The decrease of $6.6 million was primarily related to a decrease of $12.3 million in consulting fees, a decrease of $3.4 million in stock-based compensation expense, partially offset by an increase of $4.1 million legal, professional and accounting fees and an increase of $3.7 million insurance expenses.

截至 2022 年 9 月 30 日的九個月期間，一般及行政費用總計 2,190 萬美元，而 2021 年同期為 2,840 萬美元。減少 660 萬美元主要與諮詢費減少 1,230 萬美元有關，減少了340 萬美元的股票補償費用，部分被增加的410 萬美元的法律、專業和會計費用以及增加的370 萬美元的保險費用所抵消。

The nine month period also includes G&A costs related to ZYESAMI and to COVID vaccine development, which are costs that we do not expect to incur going forward.

這九個月的時間還包括與 ZYESAMI 和新冠疫苗開發相關的一般管理費用，我們預計未來不會產生這些費用。

With the three month period ended September 30, 2022, our net loss was $9.1 million, as compared to a net loss of $37.0 million for the three month period ended September 30, 2021. For the nine month period ended September 30, 2022, our net loss was $29.5 million, as compared to -- with the net loss of $62.7 million for the same period in 2021.

截至2022年9月30日的三個月期間，我們的淨虧損為910萬美元，而截至2021年9月30日的三個月期間的淨虧損為3700萬美元。在截至2022年9月30日的九個月期間，我們的淨虧損為3,700萬美元。淨虧損為 2,950 萬美元，而 2021 年同期淨虧損為 6,270 萬美元。

In the first quarter of 2021, the company recorded a non-cash settlement expense of $21.4 million to reflect the increased fair value of the Gen warrant on its grant date. We had no settlement expenses for the nine month period ended September 30, 2022.

2021年第一季度，該公司記錄了2,140萬美元的非現金結算費用，以反映Gen認股權證在授予日公允價值的增加。截至 2022 年 9 月 30 日的九個月期間，我們沒有結算費用。

Now I'd like to comment on our cash resources. As of September 30, 2022, we reported a cash balance of $18.2 million. Last week, we announced the debt financing that added net proceeds of $10 million to our balance sheet that will support our clinical trials and other operational activities. This note has an interest rate of 9% per annum and has a maturity date of 18-months. Additional details regarding the note may be found in the company's Form 8-K, which was filed on November 9, with the Securities and Exchange Commission.

現在我想談談我們的現金資源。截至 2022 年 9 月 30 日，我們報告的現金餘額為 1,820 萬美元。上週，我們宣布了債務融資，為我們的資產負債表增加了 1000 萬美元的淨收益，這將支持我們的臨床試驗和其他營運活動。該票據的年利率為 9%，到期日為 18 個月。有關該票據的更多詳細資訊可以在該公司於 11 月 9 日向美國證券交易委員會提交的 8-K 表格中找到。

With this financing, we believe that we have sufficient funds to support our clinical development plans for at least the next 12-months and if necessary the ability to reduce non-core G&A expenses if necessary. With that, I will turn it back to Stephen for closing remarks.

透過這筆融資，我們相信我們有足夠的資金來支持至少未來 12 個月的臨床開發計劃，並在必要時有能力減少非核心管理費用。說到這裡，我將把它轉回給史蒂芬做總結發言。

Thanks, Seth. This is an exciting time for NRX. We believe that NRX-101 is a potentially life saving medicine that could change the treatment paradigm for individuals with bipolar depression, but are also experiencing suicidality. This is a driving force behind our mission of meeting the needs of underserved patients with serious CNS disorders.

謝謝，塞思。對於 NRX 來說，這是一個令人興奮的時刻。我們相信 NRX-101 是一種潛在的挽救生命的藥物，可以改變雙相憂鬱症患者的治療模式，但也有自殺傾向。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 have a variety of options with regard to commercial development. Our technology and robust IP portfolio have attracted strong interest and we have been approached by a number of potential partners regarding commercial partnerships for NRX-101.

我們在商業開發方面有多種選擇。我們的技術和強大的智慧財產權組合引起了人們的濃厚興趣，許多潛在合作夥伴已就 NRX-101 的商業合作夥伴關係與我們接洽。

However, we are also prepared to support the commercial launch of this product still appove will be granted for NRX-101. We believe that due to the relatively small number of specialized psychiatric facilities in the U.S., a small company such as us is capable of marketing a first-in-class medicine to support this very high unmet medical need should our drug be approved.

不過，我們也準備好支持該產品的商業推出，但仍會批准 NRX-101。我們相信，由於美國專業精神科設施的數量相對較少，如果我們的藥物獲得批准，像我們這樣的小公司有能力銷售一流的藥物來滿足這種非常高的未滿足的醫療需求。

In addition, our team includes professionals, who have managed major debt launches to some of the world's largest pharmaceutical company. We plan to carefully evaluate all available options and make the decision that best meets the needs of patients, shareholders and NRX.

此外，我們的團隊還包括專業人士，他們曾管理過一些世界上最大的製藥公司的重大債務發行。我們計劃仔細評估所有可用選項，並做出最能滿足患者、股東和 NRX 需求的決定。

We continue to execute across our portfolio with multiple near-term catalysts on track for the fourth quarter and next year, assuming the efficacy endpoints and Phase 3 (inaudible) and Phase 3 clinical trial, we plan to initiate the rolling submission of a new drug application for the FDA by the end of next year. Operator, we are ready to take questions.

我們將在第四季度和明年繼續在我們的產品組合中執行多種近期催化劑，假設功效終點和第 3 期（聽不清楚）和第 3 期臨床試驗，我們計劃啟動新藥的滾動提交明年年底前向FDA 申請。接線員，我們準備好回答問題。

(Operator Instructions) Our first question comes from Vernon Bernadino of H.C. Wainwright.

（操作員說明）我們的第一個問題來自 H.C. 的 Vernon Bernadino。溫賴特。

Hi. Thanks for taking my question. And Steve, congrats on the progresses made since coming on board. Just a few questions regarding the clinical trials, what type of data could we expect in first quarter from the ongoing Phase 2 with NRX-101 [MDB] with SSIB, sub-acute suicidal ideation behavior? And what end points are you considering for the Phase 2study with NRX in the PTSD?

你好。感謝您提出我的問題。史蒂夫，祝賀自加入以來所取得的進步。關於臨床試驗的幾個問題，我們可以在第一季從正在進行的 NRX-101 [MDB] 與 SSIB、亞急性自殺意念行為的 2 期中期待什麼類型的數據？您考慮 NRX 在 PTSD 的第二階段研究的終點是什麼？

Could I turn that to one of my experts? Yes, let me -- go ahead, Jonathan. Go ahead.

我可以將其轉給我的專家嗎？是的，讓我——繼續，喬納森。前進。

Thank you, Vernon. On the Phase 2 trial that's currently underway, the trial is actively enrolling and we expect that by the end of the first quarter we'll be able to talk about top line data, where the endpoint is depression is measured by the mattress scale and suicidality is measured by the CTISS scale. Those are the scales where superiority was demonstrated in the Phase 2b trial.

謝謝你，弗農。目前正在進行的第二階段試驗正在積極招募中，我們預計到第一季末我們將能夠討論頂線數據，其中終點是透過床墊量表和自殺率來衡量的憂鬱症透過CTISS 量表進行測量。這些是在 2b 期試驗中證明其優越性的量表。

With regard to PTSD, again, the depression scale will be a primary endpoint. However, in that case, we're also hoping to see a difference on the CAP-5, which is a scale that directly measures symptoms of PTSD in terms of your memory, what people commonly call flashbacks and other debilitating symptoms of PTSD.

對於 PTSD，憂鬱量表將再次成為主要終點。然而，在這種情況下，我們也希望看到 CAP-5 的差異，該量表可以根據記憶力直接測量 PTSD 症狀，即人們通常所說的閃回和 PTSD 的其他衰弱症狀。

Terrific and as one follow-up regarding the manufacturing that you mentioned, what if any activities are needed to fully establish such as testing runs, the manufacturing capability or process in the U.S.? And when do you expect to have supplies from that process for your clinical trials? Thank you.

太棒了，作為您提到的製造的後續行動，如果需要任何活動來完全建立諸如測試運行、美國的製造能力或流程，該怎麼辦？您預計什麼時候可以從該流程中獲得臨床試驗的供應品？謝謝。

Well, the press release that was issued announced that the supplies for the Phase 3 clinical trial has been released and the module three manufacturing file has been filed with FDA. So there will be additional replication runs in order to demonstrate the replicability of the manufacturing practice.

那麼，發布的新聞稿宣布，三期臨床試驗的物資已經發布，並且模組三的生產文件已經向 FDA 備案。因此，將進行額外的複製運行，以證明製造實踐的可複製性。

And of course, we're sure FDA will have some comments around the manufacturing file. But as Steve emphasized, the material that's now been released for Phase 3 use was manufactured using commercial processes, so that we hope when should we demonstrate safety and efficacy that we'd be able to move directly to distribution and plant inspection with F&A for additional bridging studies.

當然，我們確信 FDA 會對生產文件提出一些評論。但正如Steve 所強調的，現在發布用於第3 階段使用的材料是使用商業流程製造的，因此我們希望何時應該證明安全性和有效性，以便我們能夠直接進行分銷和工廠檢查，並通過F&A進行額外的檢查橋樑研究。

Perfect. That's all of the questions I had today. Thank you.

完美的。這就是我今天提出的所有問題。謝謝。

Thank you for your question, Vernon.

謝謝你的提問，弗農。

The next question comes from Ed Woo of Ascendiant Capital.

下一個問題來自 Ascendiant Capital 的 Ed Woo。

Yes. Also congratulations on the progress. For PSTD, do you guys have a specific timeline when you guys would initiate for that indication?

是的。也祝賀你們的進展。對於 PSTD，你們有具體的時間表嗎？

No, I think it's too early. Our work with PTSD is in its developing stages. So once we've got some work under our belt, we'll be able to give you more of a timeline for it.

不，我認為現在還太早。我們針對創傷後壓力症候群 (PTSD) 的工作正處於發展階段。因此，一旦我們完成了一些工作，我們將能夠為您提供更多的時間表。

Great. And my last question is, have you guys thought about the international opportunity for NRX-101?

偉大的。我的最後一個問題是，你們考慮過 NRX-101 的國際機會嗎？

Yes. We have, as I mentioned, we have interest from people who are -- would like to partner with us and they have appreciated the international interest -- an international potential of NRX-101 to a great deal.

是的。正如我所提到的，我們引起了人們的興趣，他們願意與我們合作，並且他們讚賞國際上的興趣，即 NRX-101 的國際潛力。

And, you know, those who follow the literature closely will note that France has actually published perhaps the most extensive trial of ketamine for treatment of suicidal depression, both in the context of major depressive disorder and bipolar depression. And in fact, that trial showed that bipolar depression was much more susceptible to effective treatment with an NMDA antagonist, the major depressive disorder. So there is considerable interest being demonstrated in our pipeline if you follow the published literature.

而且，你知道，那些密切關注文獻的人會注意到，法國實際上已經發表了可能是最廣泛的氯胺酮治療自殺性憂鬱症的試驗，無論是在重度憂鬱症還是雙相憂鬱症的背景下。事實上，該試驗顯示雙相憂鬱症更容易受到 NMDA 拮抗劑（重度憂鬱症）的有效治療。因此，如果您關注已發表的文獻，就會對我們的管道表現出相當大的興趣。

Great. Well, thanks for answering my question and I wish you guys good luck. Thank you.

偉大的。好的，感謝您回答我的問題，祝你們好運。謝謝。

Thank you, Ed, We appreciate your being with us.

謝謝你，艾德，我們謝謝你和我們在一起。

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

我們的問答環節到此結束。我想將會議轉交蘇珊梅塞雷 (Suzanne Messere) 發表閉幕詞。

Thank you, Andrea. We would also like to address a couple of questions that we have received. And this question will go to our management team, and it is how is NRX Pharmaceuticals preparing for the Phase 3 study and potential NDA submission in 2023?

謝謝你，安德里亞。我們也想回答我們收到的幾個問題。這個問題將向我們的管理團隊提出，即 NRX Pharmaceuticals 如何準備 3 期研究和 2023 年潛在的 NDA 提交？

Well, as we've said in the call, we are planning to initiate the Phase 3 targeting bipolar with a acute suicidality by year end. We have identified as CRO, we are working with our principal investigator, we have several confirmed clinical sites for our trial. Further information will be on the website clinicaltrials.gov.

嗯，正如我們在電話中所說，我們計劃在年底前啟動針對具有急性自殺傾向的躁鬱症的第三階段。我們已經確定為 CRO，我們正在與我們的首席研究員合作，我們有幾個已確認的臨床試驗地點。更多資訊將在 ClinicalTrials.gov 網站上公佈。

We've invested in developing commercial manufacturing processes, full tech transfer was recently completed and corresponding manufacturing file update was submitted to the FDA. So those are some of the things, but not all by any means than we're doing as we prepare for our Phase 3.

我們投資開發商業製造工藝，最近完成了全面的技術轉讓，並向 FDA 提交了相應的製造文件更新。這些是其中一些事情，但絕不是我們在為第三階段做準備時所做的全部事情。

Thank you, Stephen. And then we have one additional question. The healthcare environment is increasingly cost constrained. What feedback have you gotten from payers regarding the use of your investigational medicine?

謝謝你，史蒂芬。然後我們還有一個問題。醫療保健環境的成本日益受到限制。關於您的研究藥物的使用，您從付款人那裡得到了哪些回饋？

In today's reality, the only approved therapy patients with suicidal bipolar depression have is electroshock therapy. Our analysis of payer data suggests that such patients incur more than $40,000 in annual healthcare costs, experienced multiple hospitalizations and tragically harmed themselves all too often.

在當今的現實中，自殺性雙相憂鬱症患者唯一被批准的治療方法是電擊療法。我們對付款人數據的分析表明，此類患者每年要承擔超過 40,000 美元的醫療費用，經歷過多次住院治療，並且經常悲慘地傷害自己。

A research with payers and prescribers regarding the likely marketplace acceptance of an oral medication that could benefit patients with suicidal ideation and behavior show the high interest. The feedback we received demonstrated strong support for such a mitigation, payers are aware of the high-class of hospitalization that can go up to two weeks and indicated that costs of less than $10,000 per patient for therapy should we experience no formulary restrictions for treating patients might be a positive development.

一項針對付款人和處方者的研究表明，市場對口服藥物可能的接受程度可能使有自殺意念和行為的患者受益，這項研究顯示出人們的高度興趣。我們收到的回饋表明了對這種緩解措施的強烈支持，付款人知道住院治療的等級可能長達兩週，並表明如果我們對治療患者沒有規定的限制，每位患者的治療費用將低於10,000 美元可能是一個積極的發展。

Thank you, Stephen. Actually one last question. If your drug ingredients have previously been used for other reasons, why do you have composition of matter patent protection?

謝謝你，史蒂芬。其實還有最後一個問題。如果您的藥物成分之前曾因其他原因使用過，為什麼您有物質成分專利保護？

So it's terrific. And I think I'm glad we got to have this question, because we are so -- it is so important that we have composition of medical effects with regard to our drug, it clears the field of competitors quite nicely.

所以這太棒了。我想我很高興我們有這個問題，因為我們非常重要，我們擁有與我們的藥物有關的醫療效果的成分，它很好地清除了競爭對手的領域。

D-cycloserine has been used worldwide to treat tuberculosis, but it has largely been replaced by newer anti-infectives in part because of its propensity to cause hallucinations. Lurasidone has been used to treat schizophrenia and bipolar depression, but bears a black box warning, because of its propensity when shared with all drugs of its class to cayse Akathisia and suicidal ideation.

D-環絲胺酸已在世界各地用於治療結核病，但它已在很大程度上被新型抗感染藥物所取代，部分原因是它容易引起幻覺。魯拉西酮已被用於治療精神分裂症和雙相抑鬱症，但帶有黑框警告，因為它與所有同類藥物共用時有導致靜坐不能和自殺意念的傾向。

Our co-founder, Professor Daniel Javitt, who is one of the world's 1000 most quoted scientists, discovered the unique synergy to between NMDA antagonist, such as D-cycloserine and 5HT2a antagonist, such as lurasidone, when these classes of drugs are administered together, the 5HT2s component is shown to block the hallucinations that would otherwise be caused by the NMDA drug.

我們的共同創辦人Daniel Javitt 教授是世界上被引用最多的1000 名科學家之一，他發現當這些類別的藥物一起服用時，NMDA 拮抗劑（例如D-環絲氨酸）和5HT2a 拮抗劑（例如魯拉西酮）之間存在獨特的協同作用，5HT2s 成分被證明可以阻止 NMDA 藥物引起的幻覺。

And the NMDA component is shown to block the active seizure that would otherwise be caused by 5HT2a drugs prior to this discovery by Dan Jevitt, the synergy had never been identified and it's now deemed by patent examiners all over the world to constitute a novel composition of matter.

在 Dan Jevitt 發現這一發現之前，NMDA 成分被證明可以阻止由 5HT2a 藥物引起的主動癲癇發作，這種協同作用從未被確定，現在世界各地的專利審查員認為它構成了一種新的組合物事情。

Thank you once again. And thank you to everyone for participating today, that is all the time we have for questions. And this concludes the NRX Pharmaceuticals third quarter 2022 results conference call. And again, thank you all for participating. Andrea, we're ready to close the call.

再一次感謝你。感謝大家今天的參與，這是我們提問的時間。 NRX Pharmaceuticals 2022 年第三季業績電話會議至此結束。再次感謝大家的參與。安德里亞，我們準備結束通話了。

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

會議現已結束。感謝您參加今天的演示，您現在可以斷開連接了。