Company Performance - Spero Therapeutics reported a quarterly loss of $0.25 per share, which was better than the Zacks Consensus Estimate of a loss of $0.55, representing an earnings surprise of 54.55% [1] - The company posted revenues of $5.87 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 46.60%, compared to revenues of $9.27 million a year ago [2] - Over the last four quarters, Spero Therapeutics has surpassed consensus EPS estimates two times and topped consensus revenue estimates two times [2] Stock Outlook - Spero Therapeutics shares have declined approximately 40.8% since the beginning of the year, while the S&P 500 has only declined by 0.6% [3] - The current consensus EPS estimate for the upcoming quarter is -$0.32 on $11 million in revenues, and for the current fiscal year, it is -$2.32 on $60 million in revenues [7] - The estimate revisions trend for Spero Therapeutics is currently unfavorable, resulting in a Zacks Rank 4 (Sell), indicating expected underperformance in the near future [6] Industry Context - The Medical - Biomedical and Genetics industry, to which Spero Therapeutics belongs, is currently in the top 35% of over 250 Zacks industries, suggesting a favorable industry outlook [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can impact Spero Therapeutics' stock performance [5]

[Spero Therapeutics First Quarter 2025 Operating Results](index=1&type=section&id=Spero%20Therapeutics%20First%20Quarter%202025%20Operating%20Results) [Business Overview and Highlights](index=1&type=section&id=Business%20Overview%20and%20Highlights) Spero Therapeutics reported Q1 2025 results, highlighting the successful execution of the tebipenem HBr clinical program with an interim analysis of the Phase 3 PIVOT-PO trial expected in Q2 2025, and confirmed financial runway into Q2 2026 with existing cash and GSK milestone payments - The company's top priority is the execution of the tebipenem HBr clinical program, which aims to provide an oral carbapenem option for complicated urinary tract infections (cUTI) to reduce hospital stays[2](index=2&type=chunk) - A pre-specified interim analysis of the ongoing Phase 3 PIVOT-PO clinical trial of tebipenem HBr is on track for completion in Q2 2025[5](index=5&type=chunk)[6](index=6&type=chunk) - Spero projects its existing cash, combined with earned development milestones from GSK, will fund operating expenses and capital expenditures into Q2 2026[5](index=5&type=chunk) [Pipeline Update](index=1&type=section&id=Pipeline%20Update) The company's pipeline focuses on the lead candidate tebipenem HBr for cUTI, advancing in a Phase 3 trial with GSK, while the SPR720 program for NTM-PD was suspended in late 2024 after its Phase 2a study failed to meet its primary endpoint [Tebipenem HBr](index=1&type=section&id=Tebipenem%20HBr) Tebipenem HBr is an investigational oral carbapenem antibiotic for cUTI and AP, currently in a Phase 3 PIVOT-PO trial comparing it to intravenous imipenem-cilastatin, with commercialization rights licensed to GSK for most territories - Tebipenem HBr is being developed as an oral treatment for cUTI and AP, potentially reducing the duration of in-patient therapy[3](index=3&type=chunk) - The Phase 3 PIVOT-PO trial's primary endpoint is a combination of clinical cure and favorable microbiological response at the Test-of-Cure (TOC) visit[6](index=6&type=chunk) - GSK holds an exclusive license to commercialize tebipenem HBr in all territories except for certain Asian territories retained by Meiji[3](index=3&type=chunk) [SPR720](index=1&type=section&id=SPR720) SPR720, an investigational oral prodrug for NTM-PD, had its development program suspended in Q4 2024 after a Phase 2a study's interim analysis did not meet its primary endpoint, with full data analysis underway to determine future steps - SPR720 targets the ATPase site of DNA gyrase B in mycobacteria, a mechanism distinct from other antibiotics used for NTM-PD[4](index=4&type=chunk) - The oral development program in NTM-PD was suspended in Q4 2024 after a Phase 2a study's interim analysis of 16 patients did not meet its primary endpoint[11](index=11&type=chunk) - Spero is completing the analysis of data from all 25 patients dosed in the Phase 2a study to decide on the future of the program[11](index=11&type=chunk) [Corporate Update](index=2&type=section&id=Corporate%20Update) Spero announced the appointment of Esther Rajavelu as President and Chief Executive Officer, effective May 2, 2025, who will also continue as Chief Financial Officer and Treasurer and has been nominated for the Board of Directors - Esther Rajavelu was appointed President and Chief Executive Officer, effective May 2, 2025[7](index=7&type=chunk) - Ms. Rajavelu will continue to hold her roles as Chief Financial Officer and Treasurer and has been nominated for election to the Board of Directors[7](index=7&type=chunk) [First Quarter 2025 Financial Results](index=2&type=section&id=First%20Quarter%202025%20Financial%20Results) Spero Therapeutics reported a net loss of **$13.9 million** for Q1 2025, an increase from **$12.7 million** in Q1 2024, with total revenues decreasing to **$5.9 million** from **$9.3 million** primarily due to lower grant revenue, ending the quarter with **$48.9 million** in cash and cash equivalents [Financial Performance Summary](index=2&type=section&id=Financial%20Performance%20Summary) For Q1 2025, Spero's revenue declined to **$5.9 million** from **$9.3 million** in Q1 2024 primarily due to reduced grant revenue, leading to a net loss of **$13.9 million** or **$(0.25)** per share, despite decreased R&D expenses and increased G&A expenses Q1 2025 vs Q1 2024 Key Financials | Metric | Q1 2025 ($M) | Q1 2024 ($M) | | :--- | :--- | :--- | | Total Revenue | $5.9M | $9.3M | | R&D Expenses | $13.6M | $17.3M | | G&A Expenses | $6.8M | $5.9M | | Net Loss | $(13.9)M | $(12.7)M | | Net Loss Per Share | $(0.25) | $(0.24) | - The decrease in revenue was primarily due to a decrease in grant revenue, partially offset by higher collaboration revenue related to the GSK agreement[11](index=11&type=chunk) - The decrease in R&D expenses was primarily due to lower expenditure on the SPR720 clinical program[11](index=11&type=chunk) [Condensed Consolidated Balance Sheet](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheet%20Data) As of March 31, 2025, Spero's total assets decreased to **$77.7 million** from **$110.5 million** at year-end 2024, with cash and cash equivalents at **$48.9 million** and total liabilities decreasing to **$43.9 million** from **$64.4 million** Balance Sheet Data (in thousands) | Account | March 31, 2025 (USD Thousands) | December 31, 2024 (USD Thousands) | | :--- | :--- | :--- | | Cash and cash equivalents | $48,887 | $52,889 | | Total assets | $77,709 | $110,543 | | Total liabilities | $43,895 | $64,420 | | Total stockholder's equity | $33,814 | $46,123 | [Condensed Consolidated Statements of Operations](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) For Q1 2025, Spero reported total revenues of **$5.9 million**, down from **$9.3 million** in Q1 2024, resulting in an increased net loss of **$13.9 million** or **$(0.25)** per share, compared to a net loss of **$12.7 million** or **$(0.24)** per share in the prior-year period, despite reduced total operating expenses Statement of Operations for the Three Months Ended March 31 (in thousands) | Account | 2025 (USD Thousands) | 2024 (USD Thousands) | | :--- | :--- | :--- | | Total revenues | $5,874 | $9,267 | | Research and development | $13,606 | $17,332 | | General and administrative | $6,824 | $5,917 | | Loss from operations | $(14,731) | $(13,982) | | Net loss | $(13,866) | $(12,669) | | Net loss per share, diluted | $(0.25) | $(0.24) |

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2025 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38266 SPERO THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware 46-4590683 (State or other juris ...

Core Viewpoint - Spero Therapeutics is focused on advancing its tebipenem HBr clinical program, which aims to provide an oral carbapenem option for complicated urinary tract infections, with an interim analysis of the ongoing Phase 3 PIVOT-PO trial expected in Q2 2025 [2][7][8]. Financial Results - For Q1 2025, Spero reported a net loss of $13.9 million, compared to a net loss of $12.7 million in Q1 2024, resulting in a diluted net loss per share of $0.25 versus $0.24 in the prior year [9][18]. - Total revenue for Q1 2025 was $5.9 million, down from $9.3 million in Q1 2024, primarily due to a decrease in grant revenue, although collaboration revenue increased [9][10]. - Research and development expenses decreased to $13.6 million in Q1 2025 from $17.3 million in Q1 2024, mainly due to lower spending on the SPR720 clinical program [15]. - General and administrative expenses rose to $6.8 million in Q1 2025 from $5.9 million in Q1 2024, attributed to higher personnel-related costs and consulting fees [15]. - As of March 31, 2025, Spero had cash and cash equivalents of $48.9 million, which, along with expected milestone payments from GSK, is projected to fund operations into Q2 2026 [15]. Pipeline Update - Tebipenem HBr is being developed for the treatment of complicated urinary tract infections (cUTI), including acute pyelonephritis (AP), with the goal of reducing inpatient therapy duration [3][8]. - The oral development program for NTM-PD was suspended in Q4 2024 after an interim analysis indicated it did not meet its primary endpoint [8]. Corporate Update - Esther Rajavelu was appointed as President and CEO of Spero effective May 2, 2025, and has been nominated for election to the Board of Directors [5].

Core Viewpoint - Spero Therapeutics has appointed Esther Rajavelu as President and CEO, effective May 2, 2025, following her role as Interim President since January 2025, and she will also be nominated for the Board of Directors [1][2][3] Leadership Transition - Esther Rajavelu has been recognized for her leadership and focus on advancing Spero's programs and partnerships, particularly with GSK [2] - Rajavelu will continue her roles as Chief Financial Officer and Treasurer while succeeding Sath Shukla, who will step down from both his CEO position and the Board of Directors [3] Clinical Development Focus - The company is prioritizing the PIVOT-PO Phase 3 trial for tebipenem HBr, with an update expected this quarter [3] - The clinical program for tebipenem HBr is highlighted as the highest priority for Spero, indicating a strong commitment to advancing this treatment [3] Company Overview - Spero Therapeutics is a clinical-stage biopharmaceutical company based in Cambridge, Massachusetts, focusing on novel treatments for rare diseases and multi-drug resistant bacterial infections [4]

Spero Therapeutics (SPRO) Q4 2024 Earnings Call March 27, 2025 10:33 PM ET Company Participants Shai Biran - Investor RelationsEsther Rajavelu - Interim CEO & CFOTimothy Keutzer - COO Conference Call Participants Gavin Clark-Gartner - AnalystAthena Chin - Biotechnology Equity Research Analyst Operator Good afternoon, and welcome to the Spirit Therapeutics Fourth Quarter and Full Year twenty twenty four Earnings Conference Call. At this time, all participants are in listen only mode. Following the company's ...

Financial Data and Key Metrics Changes - As of December 31, 2024, Spero had cash and cash equivalents of $52.9 million [22] - Total revenue for Q4 2024 was $15 million, down from $73.5 million in Q4 2023; total revenue for the year ended December 31, 2024, was $48 million compared to $103.8 million in 2023 [23] - R&D expenses for Q4 2024 were $28.8 million, up from $16.6 million in Q4 2023; for the year, R&D expenses were $97 million compared to $51.4 million in 2023 [24] - The company reported a net loss of $20.7 million for Q4 2024 and a net loss of $68.4 million for the year [25] Business Line Data and Key Metrics Changes - The tebipenem HBr program is the most advanced, currently in a Phase 3 trial aimed at treating complicated urinary tract infections [7] - SPR720, a novel gyrase B inhibitor, did not meet its primary endpoint in a Phase IIa proof-of-concept study [10][11] - Development of SPR206 has been discontinued following a thorough review and reprioritization [12] Market Data and Key Metrics Changes - There are an estimated 3.4 million episodes of complicated UTIs reported annually in the U.S., which are a leading cause of hospitalizations [14] - Complicated UTIs are often caused by multidrug-resistant pathogens, highlighting the need for effective treatments [15] Company Strategy and Development Direction - The primary focus for 2025 is the advancement of the tebipenem program, which could change the treatment paradigm for complicated UTIs by providing an oral option [8] - Following the completion of the tebipenem HBr Phase 3 trial, GSK is expected to take over regulatory and commercialization responsibilities [12] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about completing the interim analysis for the tebipenem trial in Q2 2025 and the potential for significant milestones from GSK [13][45] - The company is assessing the full data set from the SPR720 trial to determine next steps, indicating a cautious but proactive approach to its pipeline [41] Other Important Information - The company has approximately $47.5 million in earned and noncontingent development milestones from GSK, which will support operations into Q2 2026 [22] Q&A Session Summary Question: Does the trial get unblinded if the interim is successful? - Yes, if the interim is successful, the independent data monitoring committee will manage the unblinding process [29] Question: Is there any reason to keep running the trial longer even if the trial is positive early on? - Management cannot speculate on that until the interim analysis is completed [32] Question: What are the potential paths forward for SPR720? - The first step is to complete the data analysis of the full 25 patients dosed in the trial, which will inform the next steps [40]

Company Performance - Spero Therapeutics reported a quarterly loss of $0.38 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.35, and a significant decline from earnings of $0.96 per share a year ago, indicating an earnings surprise of -8.57% [1] - The company posted revenues of $15.04 million for the quarter ended December 2024, surpassing the Zacks Consensus Estimate by 21.32%, but this represents a decline from year-ago revenues of $73.52 million [2] - Over the last four quarters, Spero Therapeutics has surpassed consensus EPS estimates only once and has topped consensus revenue estimates two times [2] Stock Performance - Spero Therapeutics shares have declined approximately 13.6% since the beginning of the year, contrasting with the S&P 500's decline of -2.9% [3] - The current consensus EPS estimate for the upcoming quarter is -$0.33 on $11 million in revenues, and for the current fiscal year, it is -$0.79 on $60 million in revenues [7] Industry Outlook - The Medical - Biomedical and Genetics industry, to which Spero Therapeutics belongs, is currently ranked in the top 28% of over 250 Zacks industries, suggesting a favorable outlook compared to lower-ranked industries [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can be tracked by investors [5]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2024 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ____to____ Commission file number 001-38266 SPERO THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware 46-4590683 State or other juri ...

Pre-specified interim analysis of Phase 3 PIVOT-PO clinical trial of tebipenem HBr in complicated urinary tract infection (cUTI) is expected to be completed in Q2 2025Company expects to complete analysis of full data set from the Phase 2 study of SPR720 for treatment of Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD) and determine next steps for the programSPR206, a Phase 2 ready program for hospital and ventilator acquired bacterial pneumonia (HABP/VABP), discontinued following a review and reprior ...