Financial Data and Key Metrics Changes - Total revenue for 2025 was $14.2 million, compared to $10.2 million for 2024, indicating a year-over-year increase [16] - R&D expenses for 2025 were $10.7 million, down from $23.7 million in 2024, primarily due to reduced clinical expenses related to the PIVOT PO study [17] - The company reported a net loss of $1.7 million for 2025, significantly improved from a net loss of $17.9 million in 2024, with diluted net loss per share of $0.03 compared to $0.33 for the previous year [18] Business Line Data and Key Metrics Changes - The PIVOT PO trial for tebipenem HBr successfully met its primary endpoint and was stopped early for efficacy, which is expected to lead to cost savings and extend the cash runway into 2028 [6][10] - The positive outcome from the PIVOT PO trial supports the potential of tebipenem HBr as an oral alternative to IV carbapenem therapy for complicated urinary tract infections (CUTIs) [7][8] Market Data and Key Metrics Changes - There are approximately 2.9 million episodes of complicated urinary tract infections annually in the United States, contributing to over $6 billion in healthcare costs [11][12] - The current standard of care for many infections caused by multi-drug resistant (MDR) gram-negative bacteria is IV carbapenem antibiotics, highlighting a significant gap for effective oral alternatives [12][13] Company Strategy and Development Direction - The company aims to ensure that tebipenem HBr reaches the regulatory process and approval, which is seen as a key value driver for future growth [22] - The agreement with GSK allows for potential contingent milestones of up to $351 million, including $25 million upon GSK's submission of the U.S. regulatory filing [9][10] Management's Comments on Operating Environment and Future Outlook - Management expressed excitement about the positive results from the PIVOT PO trial, believing it brings tebipenem HBr closer to becoming the first commercial product from the company's pipeline [18] - The company is currently assessing the next steps for SPR720 after the phase 2A study did not meet its primary endpoint, indicating a cautious approach to future development [14] Other Important Information - The company had cash and cash equivalents of $31.2 million as of June 30, 2025, with additional milestone payments expected to fund operations into 2028 [15] - The trial's early stopping for efficacy has resulted in meaningful cost savings, which is a primary driver for the extended cash runway [10][15] Q&A Session Summary Question: Capital allocation strategy - The company indicated that the primary objective is to ensure tebipenem HBr reaches the regulatory process and approval, with future capital allocation decisions to be made once there is clarity on approval [21][22]

Tebipenem HBr (cUTI) - Tebipenem HBr is in Phase 3 clinical trials for complicated urinary tract infections (cUTI)[3] - The Phase 3 trial met its primary endpoint following a pre-specified interim analysis (IA) of data from 1,690 enrolled patients[18] - Approximately 2.9 million annual cUTI treatment episodes are attributed to $6+ billion in US healthcare costs[16] - Spero granted GSK an exclusive license for Tebipenem HBr (ex-Asia) and received $66 million upfront and $9 million in common stock investment[32] - Spero is eligible to receive up to $400 million in additional potential regulatory, commercial, and sales milestone payments, as well as royalties from GSK[32] - Spero qualified to receive $95 million in development milestones, with $23.75 million to be received in 2H 2025[33] SPR720 (NTM-PD) - The company has suspended its current development program for SPR720[6, 34] - An interim analysis of a Phase 2a oral study did not show sufficient separation from placebo, highlighting potential oral dose-limiting safety issues in subjects dosed at 1,000 mg orally once daily[37] Financial Foundation - Spero received $30 million upon SPA agreement with the FDA[33] - Spero to receive tiered low-single digit to low-double digit (if sales exceed $1 billion) tiered royalties on net product sales of Tebipenem HBr[33]

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].

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]