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]

Group 1 - Spero Therapeutics has decided to stop its PIVOT-PO Phase 3 trial early, following the recommendation of the IDMC [1] - The trial's objective of non-inferiority to intravenous imipenem-cilastatin was achieved [1]

Core Viewpoint - GSK and Spero Therapeutics announced the early termination of the pivotal phase 3 PIVOT-PO trial for tebipenem HBr due to efficacy, leading to a significant increase in Spero's stock price by 245.89% [1] Group 1: Trial Results and Efficacy - The trial demonstrated non-inferiority of tebipenem HBr compared to intravenous imipenem-cilastatin in treating complicated urinary tract infections (cUTIs) [3] - The Independent Data Monitoring Committee (IDMC) found no new safety concerns, with diarrhea and headache being the most reported adverse events [3] Group 2: Market Implications and Regulatory Plans - If approved, tebipenem HBr would be the first oral carbapenem antibiotic for cUTIs in the U.S., enhancing GSK's anti-infectives portfolio and addressing antimicrobial resistance [2][4] - GSK plans to collaborate with U.S. regulatory authorities to submit data for approval in 2025 [4] Group 3: Financial and Healthcare Context - The development of tebipenem HBr is supported by federal funds from various U.S. health departments, highlighting the drug's significance in addressing drug-resistant infections [5] - An estimated 2.9 million cases of cUTIs are treated annually in the U.S., with current treatments primarily requiring intravenous administration [5] Group 4: Previous Developments - This marks GSK's second anti-infective program to be halted early for efficacy in Phase 3, following the gepotidacin trials in 2022 [6] - GSK's Blujepa (gepotidacin) was approved by the FDA for uncomplicated urinary tract infections in March [6] Group 5: Licensing Agreement - In September 2022, GSK entered an exclusive license agreement with Spero Therapeutics for the development and commercialization of tebipenem HBr, excluding certain Asian markets [7]

Group 1: Market Overview - The three major U.S. stock indices opened slightly higher on May 28, with the Dow Jones up 0.05%, S&P 500 up 0.01%, and Nasdaq down 0.03% [1] - Investor focus has shifted from trade war tensions to the latest U.S. tax reform bill, with significant attention on Nvidia's upcoming earnings report [1][10] - Major tech stocks showed mixed performance, with Nvidia down 0.2% ahead of its earnings release [1] Group 2: Trade War Developments - Recent signals indicate a de-escalation in the U.S. trade war, including President Trump's postponement of high tariffs on the EU [5] - The ASEAN leaders expressed concerns over the uncertainty brought by U.S. tariffs and emphasized the need for trade diversification [5] - Current baseline tariffs are at 10%, with potential reductions for countries providing favorable conditions [5] Group 3: Tax Reform Concerns - The latest U.S. tax reform bill is projected to increase the deficit by $3.8 trillion over the next decade, with $2.2 trillion (approximately 58%) occurring in the first five years [8] - Analysts from Deutsche Bank and Morgan Stanley highlight that the deficit will remain above 6% of GDP in the coming years, with the tax reform contributing to this increase [9] Group 4: Nvidia's Earnings Expectations - Nvidia is set to release its earnings report, with analysts expecting revenue of $43.28 billion for the quarter, a year-over-year growth of 66% [11] - The anticipated net profit is around $19 billion, reflecting a 31% increase, although this growth rate is significantly lower than the previous year's 260% [11] - Market attention is on the supply situation of Nvidia's new Blackwell chips and its performance in the Middle East and China [11]

Core Insights - Spero Therapeutics and GSK announced that the Phase 3 PIVOT-PO trial for tebipenem HBr met its primary endpoint and will stop early for efficacy [1][2][3] Company Overview - Spero Therapeutics is a clinical-stage biopharmaceutical company focused on developing treatments for rare diseases and multi-drug resistant bacterial infections [10] - GSK is a global biopharma company aiming to unite science, technology, and talent to combat diseases [9] Trial Details - The PIVOT-PO trial evaluated tebipenem HBr against intravenous imipenem-cilastatin in hospitalized adult patients with complicated urinary tract infections (cUTIs) [6][7] - The trial enrolled 1,690 patients and assessed non-inferiority based on a 10% margin [7] - The primary endpoint was the overall response, which is a composite of clinical cure and microbiological eradication [2][7] Market Potential - An estimated 2.9 million cases of cUTIs are treated annually in the US, contributing to over $6 billion in healthcare costs [3][6] - Tebipenem HBr, if approved, could be the first oral carbapenem antibiotic for US patients with cUTIs [6][7] Future Plans - GSK plans to work with US regulatory authorities to include trial data in a filing expected in the second half of 2025 [2][6] - Full results from the trial will be submitted for presentation at a scientific congress and for publication in a peer-reviewed journal [2]

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) |

Financial Position - The company has an accumulated deficit of $473.5 million as of March 31, 2025, with cash and cash equivalents of $48.9 million[190]. - Cash and cash equivalents as of March 31, 2025, were $48.9 million, consisting of cash and money market accounts[254]. - Management has concluded that substantial doubt exists about the company's ability to continue as a going concern[190]. - The company expects to incur significant expenses and operating losses for at least the next year, with a cash runway sufficient to fund operations into the second quarter of 2026[190]. - Net cash used in operating activities for Q1 2025 was $4.002 million, compared to a net cash provided of $5.938 million in Q1 2024[237]. Revenue and Expenses - Total revenues for the three months ended March 31, 2025, were $5.874 million, a decrease of $3.393 million (approximately 36.6%) compared to $9.267 million in the same period of 2024[222]. - Grant revenue decreased by $4.3 million (approximately 85.0%) to $763,000 in Q1 2025, primarily due to a reduction in committed funds under the BARDA contract for tebipenem HBr[222]. - Collaboration revenue increased by $907,000 (approximately 21.6%) to $5.111 million in Q1 2025, driven by a $1.035 million increase from the GSK agreement[223]. - Total operating expenses decreased by $2.644 million (approximately 11.4%) to $20.605 million in Q1 2025, with research and development expenses down by $3.726 million (approximately 21.5%) to $13.606 million[225]. - Net loss for the three months ended March 31, 2025, was $13.866 million, an increase of $1.197 million (approximately 9.4%) compared to a net loss of $12.669 million in Q1 2024[222]. Development and Clinical Trials - Tebipenem HBr is in Phase 3 development, aiming to be the first broad-spectrum oral carbapenem for complicated urinary tract infections[189]. - The development of SPR720 has been suspended after failing to meet primary endpoints in a Phase 2a clinical trial[189]. - The company plans to prioritize advancing Phase 3 clinical trial activities for tebipenem HBr under the GSK License Agreement[190]. - Direct research and development expenses for the tebipenem HBr program increased by $869,000 (approximately 11.1%) to $8.669 million in Q1 2025[225]. Strategic Actions and Risks - The company anticipates incurring approximately $1.1 million in costs related to workforce reduction due to strategic restructuring, with $0.9 million already incurred[215]. - The company plans to mitigate funding risks through raising additional capital, potential new collaborations, and reducing cash expenditures[245]. - If the company is unable to raise additional funds, it may need to delay or terminate research and product development efforts[249]. - The company expects to finance operations through equity offerings, debt financings, government funding, collaborations, and licensing arrangements, which may dilute stockholder ownership[247]. - The company may have to relinquish valuable rights to technologies or revenue streams if it raises funds through collaborations or licensing arrangements[249]. Compliance and Market Conditions - The company received a deficiency letter from Nasdaq on February 25, 2025, due to its stock price closing below $1.00 for 30 consecutive business days[195]. - The company received a deficiency letter from Nasdaq on February 25, 2025, due to the bid price of its common stock closing below $1.00 per share for 30 consecutive business days, with a compliance deadline of August 25, 2025[250]. - The company is subject to market risk primarily related to interest income sensitivity due to changes in U.S. Treasury interest rates[254]. - The company faces exposure to foreign currency exchange rate movements, primarily the Euro, British Pound, and Australian Dollar against the U.S. dollar, although historical fluctuations have not materially impacted financial statements[254]. - The company has no off-balance sheet arrangements as defined by SEC rules[252].

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].

Investor Relations Contact: Shai Biran, PhD Spero Therapeutics IR@Sperotherapeutics.com Media Inquiries: media@sperotherapeutics.com CAMBRIDGE, Mass., May 05, 2025 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc. (Nasdaq: SPRO), a clinical-stage biopharmaceutical company, focused on identifying and developing novel treatments for rare diseases and multi-drug resistant (MDR) bacterial infections, today announced that it will report its first quarter 2025 financial results and provide a business update on Tuesday ...