Spero Therapeutics Inc (SPRO) 2025 Q2 法說會逐字稿

Good afternoon, and welcome to Spero Therapeutics Second Quarter 202 Earnings Conference Call. (Operator Instructions) Please be advised that this call is being recorded, and a replay will be available. You can find the 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 202 年第二季財報電話會議。（操作員指示）請注意，此通話正在錄音，並且可以重播。您可以在 Spero Therapeutics 網站 www.sperotherapeutics.com 上找到重播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。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 2025. The press release is 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 2025 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 Private Securities Litigation Reform Act of 1995 as amended. These forward-looking statements are based on management's current expectations and beliefs and are subject to risks, uncertainties and other factors that may cause actual results to differ materially from those indicated by such forward-looking statements. These risks, uncertainties and other factors are described in detail in Spero Therapeutics' filings with the SEC, including in the risk factors set forth in the periodic report on Form 10-Q for the second quarter ended June 30, 2025, 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根據經修訂的 1995 年《私人證券訴訟改革法案》做出的前瞻性陳述。這些前瞻性陳述是基於管理階層目前的預期和信念，並受風險、不確定性和其他因素的影響，這些因素可能導致實際結果與此類前瞻性陳述所示的結果有重大差異。這些風險、不確定性和其他因素在 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，包括今天向美國證券交易委員會提交的截至 2025 年 6 月 30 日的第二季度 10-Q 表定期報告中列出的風險因素。

Leading our call today will be Esther Rajavelu, our Chief Executive Officer and Chief Financial Officer. She will be joined by our Chief Operating Officer, Tim Keutzer. Esther will provide an update on our lead clinical program, Tebipenem HBr for complicated urinary tract infections or cUTIs. Then Tim will provide an overview of the cUTI therapeutic landscape and the unmet need we believe Tebipenem HBr could fill, followed by a brief update on SPR720. Esther will then conclude with a review of our financials before opening the call for questions.

今天主持我們電話會議的是我們的執行長兼財務長 Esther Rajavelu。我們的營運長 Tim Keutzer 將與她一起參加這項活動。Esther 將提供我們的主要臨床項目 Tebipenem HBr 的最新進展，該項目用於治療複雜性泌尿道感染或 cUTI。然後，Tim將概述 cUTI 治療前景以及我們認為 Tebipenem HBr 可以滿足的未滿足需求，然後簡要介紹 SPR720 的最新情況。然後，Esther 將對我們的財務狀況進行回顧，然後開始提問。

I will now turn the call over to Esther.

現在我將把電話轉給 Esther。

Thank you, Shai. Good afternoon, everyone, and thank you for joining our second quarter 2025 earnings and business update call. I'm very pleased to share that in May of this year, together with our development partner, GSK, we announced that the Phase 3 PIVOT-PO trial evaluating Tebipenem HBr in patients with cUTI, including pyelonephritis successfully met its primary endpoint and was stopped early for efficacy. This decision follows a recommendation from the Independent Data Monitoring Committee, or IDMC, which reviewed data from a prespecified interim analysis based on 1,690 patients enrolled in the trial.

謝謝你，Shai。大家下午好，感謝您參加我們的 2025 年第二季財報和業務更新電話會議。我很高興地告訴大家，今年 5 月，我們與開發合作夥伴 GSK 共同宣布，評估 Tebipenem HBr 對包括腎盂腎炎在內的 cUTI 患者療效的 3 期 PIVOT-PO 試驗成功達到了其主要終點，並因療效而提前停止。這項決定是根據獨立數據監測委員會 (IDMC) 的建議做出的，該委員會審查了基於參與試驗的 1,690 名患者的預先指定的中期分析數據。

The primary endpoint was overall response at the test of cure visit, a composite of clinical cure plus microbiological eradication. Tebipenem HBr demonstrated non-inferiority to intravenous imipenem-cilastatin in hospitalized adult patients with cUTI, including pyelonephritis. The positive outcome from the PIVOT-PO trial further supports our thesis that Tebipenem HBr and oral carbapenem can deliver comparable treatment outcomes to standard of care IV carbapenem therapy. The IDMC review did not identify any new safety concerns beyond what had been reported in prior Tebipenem studies. Diarrhea and headache were the two most reported adverse events.

主要終點是治癒測試時的整體反應，即臨床治癒加上微生物根除的綜合結果。對於患有複雜泌尿道感染（包括腎盂腎炎）的住院成年患者，氫溴酸替比培南的療效不劣於靜脈注射亞胺培南-西司他丁。PIVOT-PO 試驗的正面結果進一步支持了我們的論點，即氫溴酸替比培南和口服卡巴培南可以提供與標準靜脈注射卡巴培南療法相當的治療效果。IDMC 審查並未發現先前 Tebipenem 研究報告之外的任何新的安全問題。腹瀉和頭痛是報告最多的兩種不良事件。

We and GSK plan to submit the full results from PIVOT-PO for presentation at an upcoming scientific conference and for publication in a peer-reviewed journal. GSK is responsible for regulatory filings and has communicated that they plan to work with the FDA to include the PIVOT-PO data as part of an FDA filing at year-end 2025. We currently believe that FDA action is likely in the second half of 2026. Spero will support GSK in the preparation of the filing and any potential pre-approval communications with the FDA.

我們和葛蘭素史克計劃提交 PIVOT-PO 的完整結果，以便在即將舉行的科學會議上展示並在同行評審期刊上發表。GSK 負責監管備案，並已表示計劃與 FDA 合作，將 PIVOT-PO 數據納入 2025 年底的 FDA 備案文件的一部分。我們目前認為 FDA 可能會在 2026 年下半年採取行動。Spero 將協助 GSK 準備文件以及與 FDA 進行任何潛在的批准前溝通。

The PIVOT-PO study is covered by the special protocol assessment agreement entered into with the FDA in 2023. The FDA has indicated that positive and persuasive results from the PIVOT-PO, together with results from previously completed studies could be sufficient to support approval of Tebipenem HBr as a treatment for cUTI, including pyelonephritis for a limited use indication.

PIVOT-PO 研究受 2023 年與 FDA 簽訂的特殊方案評估協議的涵蓋。FDA 表示，PIVOT-PO 的積極和有說服力的結果，加上先前完成的研究的結果，足以支持批准氫溴酸替比培南作為 cUTI（包括腎盂腎炎）的有限使用適應症的治療。

As a reminder, our agreement with GSK grants them an exclusive license to develop and commercialize Tebipenem HBr in all territories, except for Japan and certain other Asian countries that are covered by our partnership with Meiji Seika Pharma Co. While Spero is responsible for the execution and cost of the PIVOT-PO trial, GSK is responsible for the execution and cost of the planned regulatory filings and commercialization activities as well as any future clinical development activities. Assuming these activities are successfully pursued, Spero could qualify for up to $351 million in contingent milestones, including $25 million when GSK submits the US regulatory filing and subsequent milestones based on commercialization and sales ramp as well as tiered royalties on net sales.

提醒一下，我們與 GSK 的協議授予他們在所有地區開發和商業化 Tebipenem HBr 的獨家許可，但日本和我們與明治製果製藥公司合作涵蓋的其他某些亞洲國家除外。 Spero 負責 PIVOT-PO 試驗的執行和成本，而 GSK 負責計劃中的監管備案和商業化活動以及任何未來臨床開發活動的執行和成本。假設這些活動成功進行，Spero 可以獲得高達 3.51 億美元的或有里程碑，其中包括葛蘭素史克提交美國監管文件時的 2500 萬美元以及基於商業化和銷售增長的後續里程碑以及淨銷售額的分級特許權使用費。

Our press release and 10-Q filed this evening include additional details on these contingent payments. Importantly, with the trial stopping early for efficacy, we have achieved meaningful cost savings in the near term, which we anticipate will extend our cash runway into 2028 based on our current operating plan.

我們今晚提交的新聞稿和 10-Q 包含有關這些或有付款的更多詳細資訊。重要的是，由於試驗因療效而提前停止，我們在短期內實現了顯著的成本節約，根據我們目前的營運計劃，我們預計這將使我們的現金流延長至 2028 年。

I will now turn the call over to Tim, who will provide additional details on the Tebi program and SPR720.

現在我將把電話轉給 Tim，他將提供有關 Tebi 計劃和 SPR720 的更多詳細資訊。

Thank you, Esther, and hello, everyone. We estimate that there are approximately 2.9 million episodes of complicated urinary tract infections each year in the United States alone. These infections typically occur in patients with structural or functional abnormalities of the urinary tract in patients requiring catheters or in patients with comorbidities such as kidney infections. They are also more likely to involve multidrug-resistant or MDR pathogens. If not properly treated, complicated UTIs can recur repeatedly or escalate into more severe conditions, including sepsis and septic shock. They are a leading cause of hospitalization and contribute to over $6 billion per year in US health care costs.

謝謝你，Esther，大家好。我們估計，光是在美國，每年就有約 290 萬例複雜性泌尿道感染。這些感染通常發生在需要導尿管的患者或患有腎臟感染等合併症的患者身上。它們也更有可能涉及多重抗藥性或 MDR 病原體。如果不及時治療，複雜性泌尿道感染可能會反覆復發或發展為更嚴重的疾病，包括敗血症和感染性休克。它們是住院的主要原因，每年造成美國醫療保健費用超過 60 億美元。

Currently, the standard of care for many infections caused by MDR gram-negative bacteria, including cUTIs, is carbapenem antibiotics. However, carbapenems are currently only available in IV form. This means patients often require inpatient admission or prolonged outpatient IV therapy, adding significant complexity and cost to their treatment. The lack of an effective, well-tolerated oral alternative has left a major gap in care.

目前，包括 cUTI 在內的多種由 MDR 革蘭氏陰性菌引起的感染的標準治療方法是卡巴培南類抗生素。然而，卡巴培南類藥物目前僅以靜脈注射形式提供。這意味著患者通常需要住院或延長門診靜脈治療時間，這大大增加了治療的複雜性和成本。由於缺乏有效且耐受性良好的口服藥物，導致治療方面存在重大空白。

If approved, we believe Tebipenem hydrobromide is well positioned to change the treatment landscape for patients with cUTIs, offering an oral option where currently IV therapy is the standard of care. We believe the product would represent a major clinical advance for patients and has the potential to create significant economic benefits for the health care system.

如果獲得批准，我們相信氫溴酸替比培南將有望改變複雜尿路感染患者的治療格局，為目前以靜脈注射療法為標準治療方法的患者提供一種口服治療選擇。我們相信該產品將代表患者的重大臨床進步，並有可能為醫療保健系統創造顯著的經濟效益。

Next, on to SPR720, our novel gyrase B inhibitor that was in a Phase 2a proof-of-concept study as an oral treatment for patients with Nontuberculous mycobacterial pulmonary disease or NTM-PD. In October of 2024, we completed a planned interim analysis of the trial, results from which 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 receiving 1,000 milligrams once daily. The assessment of the full data set of all 25 patients dosed in the trial is now complete, and we are currently determining the next steps for the program.

接下來，我們介紹 SPR720，這是我們的新型旋轉酶 B 抑制劑，目前正處於 2a 期概念驗證研究中，作為非結核分枝桿菌肺病或 NTM-PD 患者的口服治療藥物。2024 年 10 月，我們完成了該試驗的計劃中期分析，結果顯示研究未達到其主要終點。雖然有一些抗菌活性的證據，但治療組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，包括每天接受 1,000 毫克的高劑量組出現三例可逆性 3 級肝毒性。試驗中所有 25 名接受治療的患者的完整數據集的評估現已完成，我們目前正在確定該計劃的下一步。

I will now hand the call back to Esther for a review of our financials. Thank you for your attention.

我現在將把電話交還給 Esther，讓她審查我們的財務狀況。感謝您的關注。

Thank you, Tim. As of June 30, Spero had cash and cash equivalents of $31.2 million. We estimate that our existing cash and cash equivalents, together with the remaining $23.8 million in earned and noncontingent development milestone payments received from GSK in August 2025 will be sufficient to fund the company's current operating and capital expenditures into 2028.

謝謝你，提姆。截至 6 月 30 日，Spero 的現金和現金等價物為 3,120 萬美元。我們估計，我們現有的現金和現金等價物，加上 2025 年 8 月從葛蘭素史克收到的剩餘 2380 萬美元已賺取和非或有開發里程碑付款，將足以資助公司到 2028 年的當前運營和資本支出。

As I mentioned during the first part of the call, we achieved meaningful cost savings as the PIVOT-PO trial met the primary endpoint following the prespecified interim analysis with fewer enrolled patients than originally planned. These trial cost offsets are the primary driver of our extended runway.

正如我在通話第一部分中提到的那樣，我們實現了顯著的成本節約，因為 PIVOT-PO 試驗在預先指定的中期分析後達到了主要終點，而且入組的患者數量比原計劃要少。這些試驗成本抵銷是我們延長跑道的主要驅動力。

Total revenue for the second quarter of 2025 was $14.2 million compared with total revenue of $10.2 million for the second quarter of 2024. The revenue increase compared with the prior year period was primarily due to collaboration revenue from GSK.

2025 年第二季總營收為 1,420 萬美元，而 2024 年第二季總營收為 1,020 萬美元。與去年同期相比，營收增加主要得益於葛蘭素史克的合作收入。

R&D expenses for the second quarter of '25 were $10.7 million compared to $23.7 million for the same period in 2024. The decrease in R&D expenses year-over-year was primarily due to reduced clinical expense related to the PIVOT-PO study.

2025 年第二季的研發費用為 1,070 萬美元，而 2024 年同期為 2,370 萬美元。研發費用較去年同期下降主要是由於與 PIVOT-PO 研究相關的臨床費用減少。

G&A expenses for the second quarter of '25 were $5.9 million compared to $5.5 million for the same period in '24. This increase compared with the prior year period was primarily due to increased personnel and professional services expenses.

25 年第二季的一般及行政費用為 590 萬美元，而 24 年同期為 550 萬美元。與去年同期相比，這一增長主要是由於人員和專業服務費用的增加。

The company reported a net loss of $1.7 million for the second quarter of '25 compared with a net loss of $17.9 million for the second quarter of '24. Diluted net loss per share of common stock was $0.03 and $0.33 for these periods, respectively. For further details on our financials, please refer to our 10-Q filed with the SEC this evening.

該公司報告稱，25 年第二季淨虧損 170 萬美元，而 24 年第二季淨虧損 1,790 萬美元。這兩個期間的每股普通股稀釋淨虧損分別為 0.03 美元和 0.33 美元。有關我們財務狀況的更多詳細信息，請參閱我們今晚向美國證券交易委員會提交的 10-Q 報表。

Before opening the call for questions, I want to reiterate how excited we are about the positive PIVOT-PO result. We believe that Tebipenem HBr is now one step closer to being the first commercial product to emerge from Spero's pipeline with the potential to meaningfully improve the standard of care for patients with cUTI.

在開始提問之前，我想重申我們對 PIVOT-PO 的正面結果感到多麼興奮。我們相信，Tebipenem HBr 現在距離成為 Spero 管道中出現的第一個商業產品又近了一步，並有可能顯著改善 cUTI 患者的護理標準。

I want to take this opportunity to thank the patients and investigators who participated in our clinical program, our partner, GSK, for their ongoing commitment to fulfill unmet medical needs within the anti-infective therapeutic area and my colleagues here at Spero for their hard work and dedication to improve patient outcomes.

我想藉此機會感謝參與我們臨床計畫的患者和研究人員、我們的合作夥伴葛蘭素史克（GSK）對滿足抗感染治療領域未滿足的醫療需求的持續承諾，以及 Spero 的同事們為改善患者治療結果所做的辛勤工作和奉獻精神。

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

現在，我們將開始提問。操作員？

Gavin Clark, Evercore.

加文·克拉克（Gavin Clark），Evercore。

This is Gautam on for Gavin. So we have one question on the capital allocation. How working in terms of allocating capital? Would you be focusing on BD or would it go to more pipeline? Any guidance there would be helpful.

這是 Gautam 為 Gavin 表演的。因此，我們對資本配置有一個疑問。在資本配置方面如何運作？您會專注於 BD 還是會轉向更多的管道？任何指導都會有幫助。

Sure. Thanks for the question. So our primary objective is to make sure that Tebi gets through the regulatory process and gets to approval because that would be the real value driver going forward. So our runway currently considers funding, making sure that we're well funded to get that to the finish line. Following that, we would make decisions on what happens with the capital once we have line of sight into approval.

當然。謝謝你的提問。因此，我們的主要目標是確保 Tebi 通過監管流程並獲得批准，因為這將是未來真正的價值驅動力。因此，我們的跑道目前正在考慮資金，以確保我們有足夠的資金來完成這一目標。隨後，一旦獲得批准，我們就會決定如何處理資金。

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

我們的問答環節到此結束。我想將會議交還給管理階層，請他們發表閉幕詞。

Thank you, everyone, for joining the call. We will talk to you soon.

感謝大家參加此次電話會議。我們很快會和您聯絡。

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

謝謝。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。謝謝。