Spero Therapeutics Inc (SPRO) 2024 Q4 法說會逐字稿

Good afternoon and welcome to the Spero Therapeutics fourth-quarter and full-year 2024 earnings conference call. At this time, all participants are on listen-only mode. Following the company's formal remarks, we will open up the call for questions. Please be advised that this call is being recorded and a replay will be available. You can find information on the replay and further information related to today's announcement on the Spero Therapeutics website at www.sperotherapeutics.com.

下午好，歡迎參加 Spero Therapeutics 2024 年第四季和全年財報電話會議。此時，所有參與者都處於只聽模式。在公司正式發表演說後，我們將開始回答問題。請注意，本次通話正在錄音，並將提供重播。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 Shai Biran。Biran先生，請講。

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 fourth-quarter and full-year 2024. The press release is available on the Investors page of the Spero Therapeutics website.

謝謝您，接線生。感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 年第四季和全年的業務更新。新聞稿可在 Spero Therapeutics 網站的投資者頁面上查閱。

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 report on Form 10-K for the year ended December 31, 2024, filed with the SEC today.

在我們開始之前，我想提醒您，本次電話會議中提供的一些資訊包含證券法下的前瞻性陳述。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、表現或成就與這些前瞻性陳述表達或暗示的存在重大差異。與我們的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在 Spero Therapeutics 向美國證券交易委員會提交的文件中進行了詳細描述，包括其今天向美國證券交易委員會提交的截至 2024 年 12 月 31 日的年度 10-K 表收益報告中的「風險因素」部分。

Joining me on the call today are Esther Rajavelu, our Interim Chief Executive Officer and Chief Financial Officer; and Tim Keutzer, Spero's Chief Operating Officer. There will be a Q&A session following the prepared remarks.

今天與我一起參加電話會議的還有我們的臨時執行長兼財務長 Esther Rajavelu；以及 Spero 營運長 Tim Keutzer。準備好的發言後將有一個問答環節。

I will now turn the call over to Esther to begin.

現在我將把發言權交給 Esther。

Thank you, Shai. Good afternoon, everyone, and thank you for joining our full-year 2024 earnings and business update call.

謝謝你，Shai。大家下午好，感謝您參加我們的 2024 年全年收益和業務更新電話會議。

Spero Therapeutics is a clinical stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and multi-drug-resistant bacterial infections with high unmet medical need. Our most advanced clinical stage product candidate, tebipenem HBr, is in a Phase 3 trial with the potential to be the first broad-spectrum oral carbapenem to treat adult patients with complicated urinary tract infections, including acute pyelonephritis. These are patients who have limited or no alternative treatment options and would otherwise likely be treated with an IV carbapenem. Spero is co-developing tebipenem HBr with our partner, GSK.

Spero Therapeutics 是一家臨床階段生物製藥公司，專注於發現和開發針對罕見疾病和多重抗藥性細菌感染等尚未滿足的醫療需求的新療法。我們最先進的臨床階段候選產品替比培南氫溴酸桿菌正在進行 3 期試驗，有可能成為首個用於治療成年患者複雜性泌尿道感染（包括急性腎盂腎炎）的廣譜口服卡巴培南藥物。這些患者的替代治療選擇有限或根本沒有，因此他們很可能接受靜脈注射卡巴培南類藥物治療。Spero 正在與我們的合作夥伴 GSK 共同開發 tebipenem HBr。

Today, we announced that a pre-specified interim analysis in the Phase 3 PIVOT-PO clinical trial is expected to be completed in the second quarter of 2025. Our top priority for this year is the continued advancement of the tebipenem program which, if approved, has the potential to fundamentally change the treatment paradigm for complicated UTI by offering patients and prescribers a convenient oral treatment option.

今天，我們宣布，第三階段 PIVOT-PO 臨床試驗中預先指定的中期分析預計將於 2025 年第二季完成。我們今年的首要任務是繼續推進替比培南項目，一旦獲得批准，將有可能透過為患者和處方者提供便捷的口服治療選擇，從根本上改變複雜性尿路感染的治療模式。

Next, on to SPR720, our novel gyrase B inhibitor that was in a Phase 2A proof-of-concept study as an oral treatment for non-tuberculous mycobacterial pulmonary disease or NTMPD. The trial was randomized double-blind, placebo-controlled, and enrolled 25 treatment-naive or treatment-experienced patients with non-refractory NTM pulmonary disease caused by Mycobacterium avium complex or MAC infections. The primary endpoint of the study was change in bacterial load and sputum samples from baseline to the end of the 56-day treatment period. Key secondary endpoints included assessments of safety and tolerability, clinical response, PK, and certain other measures. Enrollment concluded in July 2024.

接下來介紹 SPR720，這是我們的新型促旋酶 B 抑制劑，該藥物作為非結核分枝桿菌肺病或 NTMPD 的口服治療藥物，目前處於 2A 期概念驗證研究階段。該試驗為隨機雙盲、安慰劑對照試驗，招募了 25 名患有由鳥分枝桿菌複合群或 MAC 感染引起的非難治性 NTM 肺部疾病且未接受過治療或接受過治療的患者。研究的主要終點是從基線到 56 天治療期結束的細菌負荷和痰液樣本的變化。關鍵次要終點包括安全性和耐受性評估、臨床反應、PK 和某些其他措施。報名將於 2024 年 7 月結束。

In October 2024, we completed a planned interim analysis which included 16 patients who had completed dosing and post-dose follow-up visits. Results from the interim analysis showed that the study did not meet its primary endpoint. While there was some evidence of antimicrobial activity, the treated arm did not show sufficient separation from placebo. In addition, we saw potential dose-limiting safety signals, including three cases of reversible Grade 3 hepatotoxicity in the high-dose cohort, dosed at 1,000 milligrams once daily. We are completing assessment of the full data set of all 25 patients dosed in the trial, and plan to determine next steps for the program once that is complete.

2024 年 10 月，我們完成了計畫中的中期分析，其中包括 16 名已完成給藥和給藥後追蹤的患者。中期分析結果顯示，研究未達其主要終點。儘管有一些抗菌活性的證據，但接受治療的組別與安慰劑組並沒有顯示出足夠的差異。此外，我們還看到了潛在的劑量限制性安全訊號，包括高劑量組（每天一次，劑量為 1,000 毫克）中出現三例可逆性 3 級肝毒性。我們正在完成試驗中所有 25 名接受治療的患者的完整數據集的評估，並計劃在完成後確定該計劃的下一步行動。

Lastly, on our pipeline, following a thorough review and reprioritization, we made the decision to discontinue development of SPR206, an IV-administered next-gen polymyxin antibiotic that cleared an IND in 2024 for a Phase 2 trial in hospital-acquired and ventilator-associated bacterial pneumonia.

最後，在我們的產品線中，經過徹底的審查和重新確定優先順序後，我們決定停止開發 SPR206，SPR206 是一種靜脈注射的下一代多粘菌素抗生素，該抗生素於 2024 年獲得 IND 批准，用於治療醫院獲得性和呼吸機相關性細菌性肺炎的 2 期試驗。

To date, we have made good progress on the Phase 3 trial for our lead asset, tebipenem HBr, and we look forward to completing the pre-specified interim analysis next quarter and with our partner, GSK, share an update on next steps for the program. As a reminder, following completion of the tebipenem HBr Phase 3 trial, GSK is expected to assume responsibility for regulatory and commercialization efforts. And if these are successfully pursued, Spero could qualify for about $400 million in contingent milestones, including $25 million when GSK submits an NDA and subsequent milestones based on commercialization and sales ramp.

到目前為止，我們的主要資產替比培南氫溴酸的 3 期試驗取得了良好進展，我們期待著下個季度完成預先指定的中期分析，並與我們的合作夥伴葛蘭素史克分享該計劃的下一步進展。提醒一下，在完成替比培南 HBr 第 3 期試驗後，GSK 預計將承擔監管和商業化工作的責任。如果這些目標順利實現，Spero 可以獲得約 4 億美元的或有里程碑付款，其中包括葛蘭素史克提交 NDA 時的 2500 萬美元以及基於商業化和銷售增長的後續里程碑付款。

With that, I'll turn the call over to Tim.

說完這些，我會把電話轉給提姆。

Thank you, Esther. I'll begin with tebipenem HBr and the opportunity for this product to address the unmet need in complicated UTI. There are an estimated 3.4 million episodes of complicated UTIs reported annually in the U.S. and they are a leading cause of hospitalizations. Complicated infections, as a reminder, are those that occur in patients who have a structural or functional abnormality of the urinary tract or those requiring catheterization. There can also be comorbidities such as kidney stones or kidney infections. Complicated UTIs are also more likely to be caused by multi-drug-resistant or MDR pathogens. If inadequately treated, these can recur frequently or progress to more severe conditions.

謝謝你，Esther。我首先會介紹氫溴酸替比培南以及該產品解決複雜性泌尿道感染未滿足需求的機會。據估計，美國每年報告的複雜性泌尿道感染病例約為 340 萬例，是住院的主要原因。需要提醒的是，複雜性感染是指發生在泌尿道結構或功能異常或需要導尿的患者身上的感染。也可能出現腎結石或腎臟感染等合併症。複雜性泌尿道感染也更有可能是由多重抗藥性或 MDR 病原體引起的。如果治療不充分，這些症狀可能會經常復發或發展為更嚴重的病症。

The current standard of care for many MDR gram-negative infections, including complicated UTIs, is treatment with carbapenems. However, carbapenems are currently only available as intravenous formulations. So they require inpatient admission or outpatient IV therapy, and this adds to the complexity of treatment.

目前，對於許多 MDR 革蘭氏陰性細菌感染（包括複雜性泌尿道感染）的標準治療方法是使用卡巴培南類藥物治療。然而，卡巴培南類藥物目前僅以靜脈注射劑型提供。因此他們需要住院或門診靜脈治療，這增加了治療的複雜性。

The lack of an effective, well tolerated oral alternative for MDR complicated UTIs means that patients are often subjected to prolonged IV antibiotic use. If approved, we believe tebipenem HBr has the potential to reduce length of hospitalization for patients who transition from intravenous to oral carbapenem therapy.

由於缺乏有效且耐受性良好的口服替代療法來治療多重抗藥性複雜性泌尿道感染，因此患者經常需要長期接受靜脈注射抗生素治療。如果獲得批准，我們相信氫溴酸替比培南有可能縮短從靜脈注射轉為口服卡巴培南療法的患者的住院時間。

The ongoing Phase 3 trial of PIVOT-PO, designed to support regulatory approval, is a global randomized double-blind, double-dummy clinical trial comparing tebipenem HBr to IV imipenem/cilastatin in hospitalized adult patients with complicated UTIs, including acute pyelonephritis.

PIVOT-PO 正在進行的 3 期試驗旨在支持監管部門的批准，這是一項全球隨機雙盲雙模擬臨床試驗，比較了氫溴酸替比培南與靜脈注射亞胺培南/西司他丁在住院成人複雜性尿路感染（包括急性腎盂腎炎）患者中的療效。

Patients are being randomized 1-to-1 to receive either tebipenem at a dose of 600 milligrams orally every 6 hours or IV imipenem/cilastatin given as 500 milligrams every 6 hours for a total of 7 to 10 days.

患者以 1:1 的比例隨機分配接受替比培南（劑量為每 6 小時口服 600 毫克）或靜脈注射亞胺培南/西司他丁（劑量為每 6 小時注射 500 毫克），總共 7 至 10 天。

The primary efficacy endpoint is overall response which is a composite of clinical cure and microbiological eradication. This is assessed at the test of cure visit. The primary analysis will assess non-inferiority in the microbiological intent to treat population using a 10% margin.

主要療效終點是整體反應，即臨床治癒和微生物根除的綜合。這是在治療訪問測試中進行評估的。主要分析將使用 10% 的邊界值來評估治療族群的微生物學非劣效性。

Briefly on SPR720, our decision to spin the oral development program in NTM pulmonary disease followed a pre-planned interim analysis based on 16 patients in the Phase 2A proof-of-concept trial. We're now in the process of completing analysis of the remaining data from all 25 patients that were dosed in the trial and plan to determine next steps for this program thereafter.

簡單介紹一下 SPR720，我們決定在 NTM 肺部疾病領域開展口服藥物開發計劃，這是根據第 2A 階段概念驗證試驗中的 16 名患者進行的預先計劃的中期分析做出的。我們目前正在完成對試驗中接受治療的所有 25 名患者的剩餘數據的分析，並計劃確定該計劃的後續步驟。

I'll now turn the call back to Esther to review the financials.

我現在將把電話轉回給 Esther 來審查財務狀況。

Thank you, Tim. I'll now walk you through our fourth-quarter and full-year financials. As of December 31, 2024, Spero had cash and cash equivalents of $52.9 million. We estimate that our existing cash and cash equivalents, together with the remaining $47.5 million in earned and non-contingent development milestone from GSK, will be sufficient to fund our operating expenses and capital expenditures into Q2 2026.

謝謝你，提姆。現在我將向您介紹我們第四季和全年的財務狀況。截至 2024 年 12 月 31 日，Spero 的現金和現金等價物為 5,290 萬美元。我們估計，我們現有的現金和現金等價物，加上葛蘭素史克剩餘的 4,750 萬美元收入和非或有開發里程碑，將足以資助我們到 2026 年第二季的營運費用和資本支出。

Total revenue for the fourth quarter of 2024 was $15 million, compared with total revenue of $73.5 million for the fourth quarter of 2023. Total revenue for the year ended December 31, 2024, was $48 million, compared to $103.8 million for the year ended December 31, 2023. The revenue decrease compared with the prior-year period was primarily due to a decrease in collaboration revenue from our agreements with GSK and Pfizer.

2024 年第四季總營收為 1,500 萬美元，而 2023 年第四季總營收為 7,350 萬美元。截至 2024 年 12 月 31 日止年度的總收入為 4,800 萬美元，而截至 2023 年 12 月 31 日止年度的總收入為 1.038 億美元。與去年同期相比，收入減少主要是因為我們與葛蘭素史克和輝瑞達成的協議的合作收入減少。

R&D expenses for the fourth quarter of 2024 were $28.8 million, compared to $16.6 million for the same period in 2023. R&D expenses for the year ended December 31, 2024 were $97 million, compared to $51.4 million for the year ended December 31, 2023. The increase in R&D expenses year-over-year was primarily due to increased clinical trial activity related to the Phase 3 PIVOT-PO trial for tebipenem HBr.

2024 年第四季的研發費用為 2,880 萬美元，而 2023 年同期為 1,660 萬美元。截至 2024 年 12 月 31 日止年度的研發費用為 9,700 萬美元，而截至 2023 年 12 月 31 日止年度的研發費用為 5,140 萬美元。研發費用年增主要是由於氫溴酸替比培南 3 期 PIVOT-PO 試驗相關的臨床試驗活動增加。

G&A expenses for the fourth quarter of 2024 were $7.1 million, compared to $6.4 million for the same period in 2023. This year-over-year increase was primarily due to increased consulting and professional fees in the last quarter of the year. G&A expenses for the year ended December 31, 2024, were $23.7 million, compared to $25.6 million for the year ended December 31, 2023, with lower full-year '24 expenses primarily due to decreases in personnel-related costs.

2024 年第四季的 G&A 費用為 710 萬美元，而 2023 年同期為 640 萬美元。年比成長主要由於去年最後一個季度諮詢和專業費用的增加。截至 2024 年 12 月 31 日止年度的 G&A 費用為 2,370 萬美元，而截至 2023 年 12 月 31 日止年度的 G&A 費用為 2,560 萬美元，24 年全年費用較低主要是由於人員相關成本減少。

The company reported a net loss of $20.7 million for the fourth quarter and net loss of $68.4 million for the year ended December 31, 2024. Diluted net loss per share was $0.38 and $1.27 for these periods, respectively. We reported a net income of $51.2 million for the fourth quarter of 2023 and net income of $22.8 million for the year ended December 31, 2023, respectively. Net income per share was $0.96 and $0.43 for these periods, respectively.

該公司報告第四季淨虧損為 2,070 萬美元，截至 2024 年 12 月 31 日的年度淨虧損為 6,840 萬美元。這兩個期間的每股攤薄淨虧損分別為 0.38 美元和 1.27 美元。我們報告稱，2023 年第四季的淨收入為 5,120 萬美元，截至 2023 年 12 月 31 日的年度淨收入為 2,280 萬美元。這些期間的每股淨收入分別為 0.96 美元和 0.43 美元。

For further details on our financials, please refer to our 10-K filed with the SEC today.

有關我們財務狀況的更多詳細信息，請參閱我們今天向美國證券交易委員會 (SEC) 提交的 10-K 文件。

With that, we will now open the call for questions. Operator?

現在，我們將開始提問。操作員？

Thank you. We will now begin the question-and-answer session. (Operator Instructions)

謝謝。我們現在開始問答環節。（操作員指令）

Gavin Clarke-Gartner, Evercore ISI.

加文·克拉克-加特納（Gavin Clarke-Gartner），Evercore ISI。

Thanks for taking the questions. I had a few on the tebipenem interim analysis. Maybe first, does the trial get unblinded if the interim is successful?

感謝您回答這些問題。我對替比培南的中期分析做了一些分析。也許首先，如果中期試驗成功，試驗是否會揭曉？

If the interim is successful, yes. The interim process is going to be managed by an independent data monitoring committee. And if their recommendation is that we stop the trial or stop enrollment, the management team will be unblinded at that time.

如果過渡期成功的話，是的。此臨時流程將由獨立的資料監測委員會管理。如果他們建議我們停止試驗或停止招募，管理團隊屆時將會揭曉答案。

Got it. So if it does get unblinded early, I guess what I'm wondering is even if the trial's positive early on on the ITT population, is there any reason to keep running the trial longer in order to narrow some of the error bars for some of the subgroup analyses, like specifically in the ESBL-positive population?

知道了。因此，如果確實提前揭盲，我想知道的是，即使試驗在 ITT 人群中早期就取得了陽性結果，是否有理由繼續進行更長時間的試驗，以縮小某些亞組分析的誤差範圍，特別是在 ESBL 陽性人群中？

We can't speculate on that at the moment given we're blinded and just preparing for the interim analysis. So we'll hopefully be able to respond to that once we've gotten the recommendation from the IDMC.

由於我們還沒有確定答案，而且只是在為中期分析做準備，因此我們目前無法對此進行推測。因此，我們希望在收到 IDMC 的建議後能夠對此作出回應。

Got it. What's the alpha spend on the interim?

知道了。中期的 alpha 支出是多少？

We'll be spending a small amount of alpha for the pre-specified (inaudible), but since this is a pre-specified interim, we've accounted for that alpha spend in determining the overall sample size for the study.

我們將為預先指定的（聽不清楚）花費少量的 alpha，但由於這是一個預先指定的中期，因此我們在確定研究的總體樣本量時已經考慮了該 alpha 支出。

Got it. And just my last quick question, any comments you can make on the bar for success for the interim and when in the trial it's actually conducted?

知道了。我的最後一個問題是，您能對臨時的成功標準以及審判實際進行的時間發表什麼評論嗎？

Basically, I mean, there are three scenarios that are likely, right? So either the trial meets the primary endpoint with this pre-specified interim which is the 10% non-inferiority margin. And we stop the trial or it fails or we stop the trial for futility or lastly, we continue enrolling.

基本上，我的意思是，有三種可能的情況，對嗎？因此，試驗要麼以預先指定的中期目標滿足主要終點，要麼以 10% 的非劣效性邊界。然後我們停止試驗，或試驗失敗，或我們因無效而停止試驗，或最後，我們繼續招募。

Got it. That's helpful. Thanks.

知道了。這很有幫助。謝謝。

(Operator Instructions)

（操作員指令）

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

Hi guys. Thanks for taking my question. This is [Athena Chin], on for Ritu Baral. I have a question on SPR720. As you see it now, what are the potential paths forward for SPR720? And when can we expect an update? Thank you.

嗨，大家好。感謝您回答我的問題。我是 [Athena Chin]，代替 Ritu Baral。我對 SPR720 有疑問。如您現在所見，SPR720 的潛在發展路徑有哪些？我們什麼時候可以看到更新？謝謝。

Sure. Hey there. The first step is to complete the data analysis of the full 25 patients dosed in the trial. Once we have the full picture on the data, we'll be in a better position to decide on the best path forward for the program which may include a reformulation strategy.

當然。嘿。第一步是完成對試驗中全部 25 名接受治療的患者進行數據分析。一旦我們全面掌握數據，我們將能夠更好地決定該計劃的最佳前進道路，其中可能包括重新制定策略。

We have determined that an oral path for NTMPD is unlikely given the dose -limiting Grade 3 tox at the 1,000 mg dose even though they were reversible once the drug was stopped. So step number one, complete the data analysis on the full 25 patients, and then determine the next steps.

我們已確定，鑑於 1,000 毫克劑量下的劑量限制性 3 級毒性，即使停藥後毒性可逆，NTMPD 也不太可能透過口服途徑治療。因此第一步是完成全部 25 名患者的數據分析，然後再確定下一步。

Understood. Thank you.

明白了。謝謝。

This concludes the question-and-answer session. I would like to turn the conference back over to management for any closing remarks. Please go ahead.

問答環節到此結束。我想將會議交還給管理階層，以便他們發表結束語。請繼續。

Thank you. We have a very excited setup for the year end. And we're looking forward to completing the interim analysis and providing you an update in the second quarter. Thank you for listening.

謝謝。我們對年底有一個非常興奮的安排。我們期待完成中期分析並在第二季向您提供最新情況。感謝您的聆聽。

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

會議現已結束。感謝您參加今天的演講。您現在可以斷開連線。