Spero Therapeutics Inc (SPRO) 2024 Q2 法說會逐字稿

Good afternoon, and welcome to the Spero Therapeutics second-quarter 2024 financial results conference call. (Operator Instructions) Please be advised that this call is being recorded and a replay will be available.

下午好，歡迎參加 Spero Therapeutics 2024 年第二季財務業績電話會議。（操作員說明）請注意，此通話正在錄音，並且可以重播。

You can find information on the replay and further information related to today's announcements on the Spero Therapeutics' website at www.sperotherapeutics.com.

您可以在 Spero Therapeutics 網站 www.sperotherapeutics.com 上找到有關重播的資訊以及與今天公告相關的更多資訊。

At this time, I would like to turn the call over to Shai Biran, Senior Director, Investor Relations. Mr. Biran, please go ahead.

現在，我想將電話轉給投資者關係高級總監 Sha Biran。比蘭先生，請繼續。

Thank you, operator, and thank you, all, for participating in today's conference call. This afternoon, Spero Therapeutics released financial results and provided a business update for the second quarter of 2024. The press releases available on the investor page of the Spero Therapeutics' website.

謝謝接線員，也謝謝大家參加今天的電話會議。今天下午，Spero Therapeutics 發布了財務業績，並提供了 2024 年第二季的業務更新。新聞稿可在 Spero Therapeutics 網站的投資者頁面上查看。

Before we begin, I would like to remind you that some of the information presented on this conference call contains forward-looking statements under the securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our actual clinical programs, future results, progress, timing, performances or achievements to differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties associated with our business and factors that could cause or contribute to such differences are described in detail in Spero Therapeutics' filings with the SEC, including in the risk factors section of its earnings and earnings report on Form 10-Q for the quarter ended June 30, 2024 filed with the SEC today.

在開始之前，我想提醒您，本次電話會議中提供的一些資訊包含證券法規定的前瞻性陳述。這些前瞻性陳述涉及重大風險和不確定性，可能導致我們的實際臨床計劃、未來結果、進展、時間安排、績效或成就與此類前瞻性陳述明示或暗示的內容有重大差異。Spero Therapeutics 向 SEC 提交的文件中詳細描述了與我們業務相關的這些風險和不確定性以及可能導致或促成此類差異的因素，包括其收益和 10-Q 表收益報告的風險因素部分。年6 月30 日的季度已於今天向SEC 提交。

We also ask that you reference the cautionary statements are forward-looking statements included with the slide presentation accompanying this conference call. Participating in today's call are Sath Shukla, Chief Executive Officer; and Esther Rajavelu, Chief Financial Officer and Chief Business Officer. Sath Shukla will begin the discussion. Please go ahead, sir.

我們也要求您參考本次電話會議附帶的投影片簡報中所包含的前瞻性聲明。參加今天電話會議的有執行長 Sath Shukla；財務長兼首席商務官 Esther Rajavelu。薩斯·舒克拉將開始討論。請繼續，先生。

Thank you, Shai. Good afternoon, everyone, and thank you for joining our conference call today. I am pleased to provide an update on the ongoing progress across our portfolio of clinical stage assets.

謝謝你，謝。大家下午好，感謝您今天參加我們的電話會議。我很高興提供有關我們臨床階段資產組合的持續進展的最新資訊。

Before that, I would like to note a change in our executive leadership team with the departure of our Chief Medical Officer, Dr. Kamal Hamed. On behalf of the Board, management and all of our employees, we thank Dr. Hamed for his many contributions to Spero and wish him every success for the future. We are pleased to announce that Dr. John Pottage, a distinguished industry veteran in our field and a member of Spero's Board for the last six years, will help oversee and provide strategic guidance for our clinical programs during this transitionary period while we continue the search for our next Chief Medical Officer.

在此之前，我想指出隨著我們的首席醫療官 Kamal Hamed 博士的離職，我們的執行領導團隊發生了變化。我們代表董事會、管理層和所有員工感謝 Hamed 博士為 Spero 做出的眾多貢獻，並祝福他未來一切順利。我們很高興地宣布，John Pottage 博士是我們領域的一位傑出的行業資深人士，也是過去六年 Spero 董事會的成員，他將在我們繼續尋找的過渡期間幫助監督我們的臨床項目並提供戰略指導。我們的下一任首席醫療官。

Moving to our clinical pipeline. Let me begin with SPR720, which we are developing as a first-line oral agent for nontuberculous mycobacterial pulmonary disease, or NTMPD. NTMPD has an estimated patient population of 245,000 patients in the US, EU, and Japan, with approximately 95,000 of those patients in the US. There is currently no approved first-line therapy for these patients.

轉向我們的臨床管道。讓我從 SPR720 開始，我們正在開發它作為非結核分枝桿菌肺病 (NTMPD) 的一線口服藥物。NTMPD 在美國、歐盟和日本估計有 245,000 名患者，其中約 95,000 名患者在美國。目前還沒有批准用於這些患者的第一線治療。

The current guidelines recommend off-label TV drugs, which have a history of lack of efficacy as well as serious tolerability issues. SPR720 has a novel mechanism of action that is different from other standard of care agents, as well as those in development for NTMPD. Spero has conducted extensive in vitro and in vivo studies, which have shown no evidence of cross resistance against marketed antibiotics as well as a low propensity for selection of resistance. Further, we have demonstrated SPR720 to be potent against multiple NTM pathogens.

目前的指引建議使用標籤外電視藥物，這些藥物歷史上缺乏療效並且有嚴重的耐受性問題。SPR720 具有不同於其他標準護理藥物以及正在開發的 NTMPD 藥物的新穎作用機制。Spero 進行了廣泛的體外和體內研究，沒有證據表明對市售抗生素存在交叉抗藥性，且抗藥性選擇的傾向也較低。此外，我們也證明 SPR720 對多種 NTM 病原體有效。

Overall, we believe the preclinical data supports SPR720's potential for therapeutic benefit. In Q4, we expect to share a comprehensive data set from our ongoing and recently completed clinical studies. This is anticipated to include data from the Phase 2A proof-of-concept study in treatment-naive and treatment-experienced non-refractory patients.

總體而言，我們相信臨床前數據支持 SPR720 的治療益處潛力。在第四季度，我們預計將分享我們正在進行和最近完成的臨床研究的全面數據集。預計這將包括未接受治療和經歷過治療的非難治性患者的 2A 期概念驗證研究的數據。

We will also report data from two supported Phase 1 studies in healthy volunteers. One of which assesses SPR720 exposure in lung as monotherapy, and the second of which assesses exposure in plasma when co-administered with standard-of-care agents azithromycin and ethambutol. The Phase 2A clinical trial compares two doses of SPR720, 500 mgs and 1,000 mgs, administered as monotherapy versus placebo in patients with NTMPD due to M-avium complex, or MAC.

我們也將報告兩項支持的健康志願者第一階段研究的數據。其中一項評估單藥治療時 SPR720 在肺部的暴露，第二項評估與標準治療藥物阿奇黴素和乙胺丁醇聯合給藥時血漿中的暴露。2A 期臨床試驗比較了兩種劑量的 SPR720（500 毫克和 1,000 毫克），分別作為單一療法與安慰劑治療因 M-avium 複合物（MAC）引起的 NTMPD 患者。

We have enrolled a total of 25 patients, including those treatment-naive and treatment-experienced patients who do not have treatment refractory disease. It is our hope that the data from this study further indicate that SPR720 as a monotherapy can decrease the NTM bacteria load over the treatment course of 56 days. To analyze this early bactericidal activity, we are measuring changes in bacterial loads in patients’ distribution, including the rate of change in long-term colony forming units per millimeter, which is our primary endpoint in this study.

我們總共入組了 25 名患者，包括那些未曾接受過治療和接受過治療但沒有治療難治性疾病的患者。我們希望這項研究的數據進一步表明，SPR720 作為單一療法可以在 56 天的治療過程中降低 NTM 細菌負荷。為了分析這種早期殺菌活性，我們正在測量患者分佈中細菌負荷的變化，包括每毫米長期菌落形成單位的變化率，這是我們本研究的主要終點。

We are also looking at the rate of change in time to positivity, which is a key secondary endpoint in the study. A clear numerical difference in these measures between the treated arm and placebo could indicate that SPR720 has a potential therapeutic effect in patients with NTMPD. We anticipate that success on these endpoints would also make SPR720 the only oral agent in development that we are aware of to demonstrate early bactericidal activity in patients with NTMPD due to MAC and which enable us to move confidentially into late-stage development.

我們也正在研究積極性時間的變化率，這是研究的一個關鍵的次要終點。治療組和安慰劑組之間這些指標的明顯數值差異可能表明 SPR720 對 NTMPD 患者俱有潛在的治療作用。我們預計，這些終點的成功也將使 SPR720 成為我們所知的唯一一種正在開發的口服藥物，可在 MAC 引起的 NTMPD 患者中顯示出早期殺菌活性，這使我們能夠秘密地進入後期開發。

Ultimately, we believe that SPR720 could be used as part of combination treatment regimens. And if the ongoing strategy confirms our expectations that the drug has monotherapy activity, we anticipate the future registration-enabling studies to be designed to include standard-of-care agents.

最終，我們相信 SPR720 可以用作聯合治療方案的一部分。如果正在進行的策略證實了我們對該藥物具有單一治療活性的預期，我們預計未來的註冊研究將包括標準治療藥物。

Complementing the Phase 2A data, as previously mentioned, we will also share data from two Phase 1 studies in healthy volunteers. The first study used a bronchoalveolar lavage, or BAL, to examine intrapulmonary pharmacokinetics of SPR719, the active moiety of the prodrug SPR720. We expect to share PK measures showing the extent of exposures in the lungs, that is the site of infection.

如前所述，為了補充 2A 期數據，我們也將分享兩項針對健康志願者的 1 期研究的數據。第一項研究使用支氣管肺泡灌洗 (BAL) 來檢查前驅藥物 SPR720 的活性部分 SPR719 的肺內藥物動力學。我們希望分享 PK 措施，顯示肺部（即感染部位）的暴露程度。

The second strategy evaluates changes in plasma PK when an SPR720 is co-administered with azithromycin and ethambutol. We anticipate this data to be informative than selecting doses in future combination studies.

第二種策略評估當 SPR720 與阿奇黴素和乙胺丁醇共同給藥時血漿 PK 的變化。我們預計這些數據比在未來的聯合研究中選擇劑量更有價值。

Lastly, we recently completed an in vitro resistant study of SPR719 in combination with standard-of-care agents and anticipate sharing these data at IDWeek in October. The team is excited about this upcoming data readout in Q4. These studies are expected to provide us with a robust data set that we will use to determine the registrational path for SPR720 as first-line oral treatment for NTMPD.

最後，我們最近完成了一項 SPR719 與標準護理藥物聯合的體外抗藥性研究，並預計在 10 月的 IDWeek 上分享這些數據。該團隊對第四季度即將公佈的數據感到興奮。這些研究預計將為我們提供可靠的數據集，我們將使用它來確定 SPR720 作為 NTMPD 一線口服治療藥物的註冊路徑。

Turning now to tebipenem HBr, which we are developing as the first potential oral carbapenem antibiotic for the treatment of complicated urinary tract infections, or cUTI. Enrollment in our ongoing Phase 3 global PIVOT-PO clinical trial is on track, and we are pleased with the progress made since the beginning of the year. Our goal remains to complete enrollment in the second half of 2025.

現在轉向氫溴酸替比培南，我們正在開發它作為第一個潛在的口服碳青黴烯類抗生素，用於治療複雜的泌尿道感染（cUTI）。我們正在進行的 3 期全球 PIVOT-PO 臨床試驗的註冊工作正在按計劃進行，我們對今年以來的進展感到滿意。我們的目標仍然是在 2025 年下半年完成入學。

Patients are randomized 1-to-1 in this pivotal Phase 3 clinical trial to receive tebipenem HBr 600 mgs orally every six hours or imipenem cilastatin 500 mgs intravenously every six, for a total of 7 to 10 days. Target enrollment is approximately 2,648 patients.

在這項關鍵的3 期臨床試驗中，患者被依照1 對1 的比例隨機分配，每6 小時口服替比培南HBr 600 毫克，或每6 小時靜脈注射亞胺培南西司他丁500 毫克，總共7 至10 天。目標入組人數約 2,648 名患者。

The primary efficacy endpoint is overall response, which is a composite of clinical and microbiological response and the test-of-cure visit. The primary analysis for the trial will be an assessment of non-inferiority in the microbiological intent-to-treat population based on a 10% non-inferiority margin. As a reminder, tebipenem HBr is partnered with GSK. We are responsible for the execution of the ongoing Phase 3 trial, and GSK is responsible for ex-US development and worldwide commercialization, excluding search and rights in Asian territories held by another partner, Meiji Seika.

主要療效終點是整體反應，它是臨床和微生物反應以及治癒測試訪視的綜合結果。本試驗的主要分析將基於 10% 的非劣效性裕度評估微生物意圖治療族群的非劣效性。提醒一下，氫溴酸替比培南是與 GSK 合作的。我們負責執行正在進行的第三階段試驗，葛蘭素史克負責美國以外的開發和全球商業化，不包括另一個合作夥伴明治精化在亞洲地區的搜尋和權利。

cUTI infections are a leading cause of hospitalization in the US. The incidence is estimated to be over 3 million cases per year, which translates into a significant version on the healthcare system. Tebipenem HBr is, to our knowledge, the only oral carbapenem in development. If approved, it could address the need for an oral carbopenem in patients with complicated urinary tract infections caused by multidrug-resistant uropathogens, potentially eliminating the need for hospitalization or reducing length of stay with transition from intravenous to oral carbopenem therapy.

cUTI 感染是美國住院的主要原因。據估計，每年的發病率超過 300 萬例，這對醫療保健系統來說是一個重大影響。據我們所知，氫溴酸替比培南是唯一正在開發的口服碳青黴烯類藥物。如果獲得批准，它可以解決由多重抗藥性泌尿道病原體引起的複雜尿路感染患者對口服碳青黴烯的需求，有可能消除住院需求或減少從靜脈注射到口服碳青黴烯治療過渡的住院時間。

Finally, wrapping up with SPR206. SPR206 an innovative, investigational, intravenously administered direct-acting polymyxin partnered with Pfizer for European markets. We announced that in the first quarter of this year, the FDA cleared the IND to advance SPR206 into a Phase 2 clinical trial in patients with hospital-acquired or ventilator-associated bacterial pneumonia and that the FDA also awarded SPR206 fast-track designation. As a reminder, we plan to initiate a Phase 2 study contingent on availability of non-dilutive funding.

最後以SPR206結束。SPR206 是一種創新、在開發、靜脈注射的直接作用多粘菌素，與輝瑞合作開發歐洲市場。我們宣布，今年第一季度，FDA 批准了 IND，將 SPR206 推進到醫院獲得性或呼吸器相關細菌性肺炎患者的 2 期臨床試驗中，FDA 也授予 SPR206 快速通道資格。提醒一下，我們計劃根據非稀釋資金的可用性啟動第二階段研究。

With that, I'll turn the call over to Esther to review our quarterly financial results.

這樣，我會將電話轉給艾絲特，以審查我們的季度財務表現。

Thank you, Sath, and good afternoon to all of you joining us on the call. I'll begin with our cash guidance first and then summarize our GAAP financials. Spero ended the second quarter with $63.5 million in cash and cash equivalents. In addition to the cash on our balance sheet, we anticipate three remaining tranches of development milestone payments from GSK in the approximate amount of $24 million every six months.

謝謝您，薩斯，祝所有參加我們電話會議的人下午好。我將首先從我們的現金指導開始，然後總結我們的 GAAP 財務狀況。Spero 第二季末現金及現金等價物為 6,350 萬美元。除了資產負債表上的現金之外，我們預計葛蘭素史克將每六個月支付三筆剩餘的開發里程碑付款，金額約為 2,400 萬美元。

As a reminder, upon initiation of the Phase 3 PIVOT-PO clinical trial, Spero qualified for $95 million in development milestones from GSK, which are payable in four equal installments over two years. The second tranche of approximately $24 million is payable in the third quarter of this year.

提醒一下，在 PIVOT-PO 3 期臨床試驗啟動後，Spero 有資格從 GSK 獲得 9,500 萬美元的開發里程碑資金，該資金將在兩年內分四次等額支付。第二筆約 2,400 萬美元將於今年第三季支付。

We estimate that our cash and cash equivalents, together with other non-dilutive funding commitments, will be sufficient to fund our operating expenses and capital expenditure requirements into late 2025.

我們估計，我們的現金和現金等價物以及其他非稀釋性融資承諾將足以滿足我們到 2025 年底的營運費用和資本支出需求。

Now moving on to summarize our GAAP financials. Total revenue for the second quarter of 2024 was $10.2 million compared with total revenue of $2.7 million for the second quarter of 2023. The revenue increase for the second quarter of '24 was primarily due to an increase in collaboration revenue related to our agreement with GSK and an increase in grant revenue related to our BARDA contract, both for tebipenem HBr. These were partially offset by a decrease under our NIAID agreement relating to SPR206 and collaboration revenue related to our agreement with Pfizer for SPR206.

現在繼續總結我們的 GAAP 財務狀況。2024 年第二季的總收入為 1,020 萬美元，而 2023 年第二季的總收入為 270 萬美元。2024 年第二季的營收成長主要是由於與我們與 GSK 的協議相關的合作收入的增加以及與我們的 BARDA 合約相關的贈款收入的增加，兩者都是針對氫溴酸替比培南。這些收入被我們與 SPR206 相關的 NIAID 協議的減少以及與我們與輝瑞就 SPR206 的協議相關的合作收入所部分抵消。

Research and development expenses for the second quarter of 2024 were $23.7 million compared to $9.5 million for the same period in '23. The increase in research and development expenses year over year was primarily due to higher direct costs related to the pivotal Phase 3 trial for tebipenem HBr and the Phase 2A clinical trial for SPR720, partially offset by lower direct costs related to SPR206.

2024 年第二季的研發費用為 2,370 萬美元，而 2023 年第二季的研發費用為 950 萬美元。研發費用較去年增加主要是由於氫溴酸替比培南關鍵3期試驗和SPR720 2A期臨床試驗相關的直接成本增加，部分被SPR206相關直接成本降低所抵銷。

G&A expenses for the second quarter of 2024 were $5.5 million compared to $6.1 million for the same period in '23. This year-over-year decrease was primarily due to a decrease in G&A personnel-related costs, partially offset by increases in professional and consulting.

2024 年第二季的一般管理費用為 550 萬美元，而 2023 年第二季的一般管理費用為 610 萬美元。這一同比下降主要是由於與一般管理人員相關的成本減少，但部分被專業和諮詢費用的增加所抵消。

Spero reported a net loss of $17.9 million, or $0.33 per share of common stock, basic and diluted, for the second quarter ended June 30, 2024. This compares with a net loss of $11.9 million, or $0.23 per share of common stock for the comparable period in 2023. For further details on our financials, please refer to our 10-Q filed with the SEC today.

Spero 報告稱，截至 2024 年 6 月 30 日的第二季淨虧損為 1,790 萬美元，即每股普通股（基本股和稀釋股）虧損 0.33 美元。相較之下，2023 年同期淨虧損為 1,190 萬美元，即每股普通股虧損 0.23 美元。有關我們財務狀況的更多詳細信息，請參閱我們今天向 SEC 提交的 10-Q 報告。

We will now open the call for questions. Operator?

我們現在開始提問。操作員？

(Operator Instructions) Louise Chen, Cantor Fitzgerald.

（操作員說明）Louise Chen，Cantor Fitzgerald。

Hi. Congratulations on all the progress and thanks for taking my questions here. So I have two quick questions for you.

你好。恭喜所有的進展，並感謝您在這裡提出我的問題。我有兩個簡單的問題想問你。

First one, I wanted to ask you what's the significance of the IDWeek data that you're going to present and what we think we should learn from all of this? And then second question is just on Kamal departure. You didn't give a lot of details here, but obviously, ahead of the data, people are wondering what happened here. So any color you give would be great. Thank you.

首先，我想問您將要展示的 IDWeek 資料的意義是什麼？第二個問題是關於卡邁勒的離開。您在這裡沒有提供很多細節，但顯然，在數據出現之前，人們想知道這裡發生了什麼。所以你給的任何顏色都會很棒。謝謝。

Hey, Louise. Thanks for the questions and great to hear from you. I'll answer your questions in reverse order. Kamal's departure, obviously, is an event for the company, but it has nothing to do with the data or the programs. That we can share with you. Like the rest of you, we are looking forward to the unblinding and reporting of the top-line data for SBR720 in 4Q, and then, of course, for tebipenem next year, where our enrollment continues on track and is expected to be completed in the second half of next year.

嘿，路易絲。感謝您的提問，很高興收到您的來信。我會以相反的順序回答你的問題。顯然，卡邁勒的離職對公司來說是一件大事，但與數據或程序無關。我們可以與您分享。和你們其他人一樣，我們期待第四季度 SBR720 的頂線數據揭盲和報告，當然還有明年的替比培南，我們的註冊工作將繼續按計劃進行，預計將於 2019 年完成。下半年。

Moving to your first question for IDWeek, we are particularly excited about presenting resistance data. So one of the value propositions for SPR720, as you know, is that with that novel MOA, the data we have seen to date has shown a low propensity for resistance and no evidence of cross resistance. So for IDWeek in particular, that will be a dataset we will build on.

轉向 IDWeek 的第一個問題，我們對提供阻力數據感到特別興奮。因此，如您所知，SPR720 的價值主張之一是，透過這種新穎的 MOA，我們迄今為止看到的數據顯示抗藥性傾向較低，並且沒有交叉抗藥性的證據。因此，特別是對於 IDWeek，這將是我們建立的資料集。

Thank you.

謝謝。

Gavin Clark-Gartner, Evercore ISI.

Gavin Clark-Gartner，Evercore ISI。

Hey, guys. Thanks for taking my question. I just had one. So I appreciate that you're doing the PK substudy, which includes BALs. But for both of the doses that you're testing in your Phase 2A, over a given day, roughly what duration of MIC90 coverage do you believe that 720 has at both of the doses and specifically at the site of infection? Thanks.

嘿，夥計們。感謝您提出我的問題。我剛喝了一個。所以我很感激您正在進行 PK 子研究，其中包括 BAL。但是，對於您在 2A 階段測試的兩種劑量，在給定的一天內，您認為 720 在這兩種劑量下，特別是在感染部位的 MIC90 覆蓋時間大致是多長？謝謝。

Thanks for the question, Gavin. I'll have to look back on what we have disclosed on that question and perhaps come back to you, but I do not believe that we have disclosed that data just yet. Obviously, that data will be part of what we report out. But for today, I'm not sure I can elaborate on it to the degree you ask.

謝謝你的提問，加文。我將不得不回顧我們在這個問題上所披露的內容，也許還會回到你身邊，但我不認為我們已經披露了這些數據。顯然，這些數據將成為我們報告的一部分。但今天，我不確定我能否按照您要求的程度詳細闡述它。

Great. We look forward to seeing more. Thanks.

偉大的。我們期待看到更多。謝謝。

Thanks, Gavin.

謝謝，加文。

Ritu Baral, TD Cowen.

裡圖·巴拉爾，TD·考恩。

Good afternoon, everyone. Thanks for taking the questions. So I wanted to make sure that I heard you correctly. You said that the 25 patients enrolled were -- I'm sorry if I get this wrong, were the 25 patients were all treatment-naive or did you have treatment-experienced patients in there? And, well, I'll let you answer that before my follow-up.

大家下午好。感謝您提出問題。所以我想確保我沒聽錯。你說入組的 25 名患者——如果我弄錯了，我很抱歉，這 25 名患者都沒有接受過治療，還是有接受過治療經驗的患者？而且，好吧，我會讓你在我的後續行動之前回答這個問題。

Sure. So we've always said that this trial which have treatment-naive and non-refractory treatment-experienced patients, Ritu. And that is the expectation for those 25 patients. Did that answer your question?

當然。所以我們一直說這項試驗有未接受過治療且非難治性治療經歷過的患者，Ritu。這就是這 25 名患者的期望。這回答了你的問題嗎？

Yeah. Can you speak to the mix that you ended up with final enrollment and how it might impact both the primary and secondary endpoint expectations? And then I have a follow-up.

是的。您能否談談您最終註冊的組合以及它可能如何影響主要和次要終點預期？然後我有一個後續行動。

Unfortunately, right now, we can't, Ritu, because most of those data are blinded to us. So even the mix of treatment-naive and treatment-experienced patients is not something we have disclosed just yet.

不幸的是，現在我們不能，Ritu，因為大多數數據對我們來說是盲目的。因此，即使是未接受過治療的患者和有過治療經驗的患者的混合情況也不是我們目前所揭露的。

Got it. I wanted to also ask about the secondary endpoint of time to positivity. Can you elaborate on that? I think previous drugs have discussed time to sputum negativity. Can you go into a little detail on what time to positivity is and what sort of a meaningful timepoint in that end point?

知道了。我還想問一下積極性時間的次要終點。能詳細說明一下嗎？我認為以前的藥物已經討論了痰液陰性的時間。您能否詳細說明什麼是積極的時間以及該終點的有意義的時間點是什麼？

Yeah. So I think for context, for both the primary endpoint, which is the reduction in the log10 CFU per milliliter as well as time for positivity, these are metrics that are well established and covered in TB, for example. But in NTM, of course, this being a relatively new therapeutic space, there is limited academic and medical literature that creates cutoffs, for example.

是的。因此，我認為，就背景而言，對於主要終點（即每毫升 log10 CFU 的減少以及陽性時間），這些都是已在 TB 中建立並涵蓋的指標。但當然，在 NTM 中，這是一個相對較新的治療領域，例如，學術和醫學文獻造成的限制是有限的。

But the way time to positivity works is that it's basically the daily prolongation of time to positivity. So it measures the time growth. In this process, the liquid media are inoculated with a sputum sample. And then when that reaches a pre-defined signal for the evidence of bacterial growth, that can indicate the efficacy of the treatment in question.

但積極性時間的運作方式基本上是每天延長積極性時間。所以它衡量的是時間成長。在此過程中，將痰液樣本接種到液體培養基中。然後，當達到細菌生長證據的預先定義訊號時，就可以顯示相關治療的功效。

So really, the longer that time to positivity, the better it is. In TB, this measure is well established. For us, it's always been a key secondary endpoint. But within TB, there's usually a high degree of correlation between what we have characterized as a primary endpoint, the log reduction, and the time to positivity. So what we hope is that as we report both of these out they will show a activity of the drug on microbial reduction.

所以說，保持積極態度的時間越長越好。在結核病領域，這項措施已充分確立。對我們來說，它一直是關鍵的次要終點。但在結核病中，我們所描述的主要終點、對數減少和陽性時間之間通常存在高度相關性。因此，我們希望當我們報告這兩種情況時，它們將顯示出該藥物對減少微生物的活性。

Thank you for the question.

謝謝你的提問。

Ram Selvaraju, HC Wainwright.

拉姆‧塞爾瓦拉朱 (Ram Selvaraju)，HC 溫賴特 (HC Wainwright)。

Hi. Thanks very much for taking my questions and congrats on all the progress. Wanted to ask about the tebipenem Phase 3 program. And if you could give us an additional granularity regarding the total number of clinical sites that are currently involved and what factors you expect to impact enrollment either positively or negatively with respect to being able to get to that enrollment completion timeline target that you disclosed in today's press release. Thank you.

你好。非常感謝您提出我的問題並祝賀所有的進展。想詢問替比培南第三階段計畫。如果您能為我們提供更多詳細信息，說明目前涉及的臨床中心總數，以及您期望哪些因素會對註冊產生積極或消極的影響，以實現您在今天披露的註冊完成時間表目標新聞稿。謝謝。

Sure. Thanks, Ram, for the question. We haven't given a precise number yet, but if you were to assume somewhere in the triple digits, it's a global study for multiple countries, you would be in the ballpark. It's a larger trial than the last one, as you know, and as we mentioned on the call, on track for enrollment.

當然。謝謝拉姆提出這個問題。我們還沒有給出準確的數字，但如果你假設是三位數，這是針對多個國家的全球研究，那麼你就差不多了。如您所知，這是比上一次更大的試驗，正如我們在電話中提到的，註冊工作正在按計劃進行。

To date, we have not seen headwinds like the one we saw for ADAPT, where COVID, of among other features, was a districting factor for us. So at this moment in time, we continue to hold to our expectation of that completion of enrollment in the second half of next year. And as you know, our partners at GSK are also setting out their timelines for an NDA submission that is also conduit for that timeframe. So the bottom line for tebi is on track, and we are excited to see the data.

到目前為止，我們還沒有看到像 ADAPT 那樣的逆風，其中新冠疫情等因素對我們來說是一個區區因素。所以此時此刻，我們仍然堅持明年下半年完成招生的期望。如您所知，我們在 GSK 的合作夥伴也制定了 NDA 提交的時間表，這也是該時間範圍的管道。因此，tebi 的底線已步入正軌，我們很高興看到這些數據。

Okay. And then just two technical questions regarding 720. First is, can you just give us a brief description of the manner in which the pro-drug 720 is converted into the active moiety 719? And secondly, if you can comment on what additional combinations or permutations, if any, you might want to look at to assess in terms of variability in plasma PK beyond azithromycin and ethambutol in the context of use of 720. Thanks.

好的。然後是關於 720 的兩個技術問題。首先，您能給我們簡單描述一下前藥720轉化為活性部分719的方式嗎？其次，如果您可以評論哪些額外的組合或排列（如果有的話），您可能需要考慮評估在使用 720 的情況下除阿奇黴素和乙胺丁醇之外的血漿 PK 的變異性。謝謝。

Sure. For the first question, Ram, we'll dig into the publications we have and send them to you. What we have stated in calls is that 720 has a very rapid conversion to its active moiety. But on the granularity, we'll just have to forward to you what we have published, so we can ensure that after the call.

當然。對於第一個問題，拉姆，我們將深入研究我們擁有的出版物並將其發送給您。我們在電話會議中指出，720 能夠非常快速地轉化為其活性部分。但就粒度而言，我們只需將我們已發布的內容轉發給您，這樣我們就可以在通話後確保這一點。

For your second question right now, so azithromycin serves as a macrolide. And so with a macrolide under discussion, we feel that, that is an appropriate measure to evaluate co-administration bid along with the ethambutol.

對於你現在的第二個問題，阿奇黴素是一種大環內酯類藥物。因此，對於正在討論的大環內酯類藥物，我們認為這是評估與乙胺丁醇共同給藥的適當措施。

But as the landscape for NTM evolves, obviously, we will be open to evaluation of what makes sense as we enter later-stage development. For today, as a oral therapy, right now, the only one in development, as you know, in first line, those are the oral therapies that make the most sense to us. But certainly, after we see the data and in discussions with the FDA, we will be evaluating all the optionality that would make sense in progressing the asset.

但顯然，隨著 NTM 格局的發展，我們將在進入後期開發時對有意義的評估持開放態度。就今天而言，作為一種口服療法，目前唯一正在開發的療法，如您所知，在第一線，這些是對我們最有意義的口服療法。但當然，在我們看到數據並與 FDA 討論後，我們將評估對推進資產有意義的所有選擇。

Thank you very much.

非常感謝。

Thank you.

謝謝。

Thank you. Ladies and gentlemen, this concludes our question-and-answer session. I would now hand the conference over to Sat Shukla for his closing comments.

謝謝。女士們先生們，我們的問答環節到此結束。我現在將會議交給薩特舒克拉 (Sat Shukla) 聽取他的總結意見。

Thank you, everyone, for dialing in. We look forward to updating you as we progress our pipeline. Have a great day.

謝謝大家撥通電話。我們期待在我們的管道進展過程中向您通報最新情況。祝你有美好的一天。

Thank you. The conference of Spero Therapeutics has now concluded. Thank you for your participation. You may now disconnect your lines.

謝謝。Spero Therapeutics 的會議現已結束。感謝您的參與。現在您可以斷開線路。