Spero Therapeutics, Inc. · NASDAQ:SPRO

Spero Therapeutics — Investor Presentation (November 2025)

20 slides from Spero Therapeutics's investor presentation, Nov 13, 2025

  1. Slide 1: Corporate Presentation October 2025

    Exhibit 99.2 Corporate Presentation October 2025

  2. Slide 2: Forward-looking Statement

    Forward-looking Statement This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including without limitation, statements regarding, among other things, the potential number of patients who could be treated by tebipenem H

  3. Slide 3: Developing Therapies for Rare and Multi-drug Resistant Infectious Diseases

    Developing Therapies for Rare and Multi-drug Resistant Infectious Diseases Tebipenem HBr Clinical stage positioned as first Strong financial portfolio oral carbapenem foundation for cUTI • cUTI represents an important • Indications with high • Healthy balance sheet with cash health issue, with ~2.9

  4. Slide 4: Maturing Pipeline with Differentiated Clinical Assets

    Maturing Pipeline with Differentiated Clinical Assets Asset Indication Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestone Partnered Assets Tebipenem HBr Phase 3 complete; cUTI US regulatory submission Worldwide, Asia 1 expected in 2H 2025 ex. Asia Wholly Owned First-line Complete data analysi

  5. Slide 5: Tebipenem HBr Oral Carbapenem for cUTI

    Tebipenem HBr Oral Carbapenem for cUTI 5

  6. Slide 6: Complicated Urinary Tract Infection (cUTI)

    Complicated Urinary Tract Infection (cUTI) Complicated Uncomplicated • cUTIs are associated with an abnormality of Functional or anatomical No functional or anatomical the urinary tract or in the presence of abnormality of urinary tract abnormality of urinary tract catheterization 1 • Patients with

  7. Slide 7: Overview of cUTI Therapeutic Landscape

    Overview of cUTI Therapeutic Landscape Resistance and lack of effective treatments Lack of effective oral treatment options has result in a large addressable cUTI patient resulted in increased – population • Outpatient visits • Emergency department visits IV Therapy/ nd • Outpatient IV use 2 line Or

  8. Slide 8: Tebipenem HBr: Positioned to Change the Treatment Landscape for cUTI Patients

    Tebipenem HBr: Positioned to Change the Treatment Landscape for cUTI Patients Potential first-to-market Phase 3 stopped for Global commercial oral carbapenem efficacy partnership • Orally bioavailable carbapenem • Trial met primary endpoint • Out-licensed global prodrug that rapidly converts to foll

  9. Slide 9: Tebipenem HBr Phase 3 Clinical Trial in cUTI (PIVOT-PO)

    Tebipenem HBr Phase 3 Clinical Trial in cUTI (PIVOT-PO) A Phase 3, Randomized, Double-blind, Double-dummy, Multi-center Study to Assess the Efficacy and Safety of Orally Administered Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr), Compared to Intravenously Administered Imipenem-cilastatin in Patients w

  10. Slide 10: Phase 3 Met Primary Endpoint

    Phase 3 Met Primary Endpoint Trial stopped early for efficacy at pre-specified Interim Analysis Tebipenem HBr Imipenem-cilastatin Adjusted treatment (oral, 600 mg, every 6 hours) (IMI-CIL) (IV, 500 mg, difference every 6 hours) Overall response at test 58.5% (261/446) 60.2% (291/483) −1.3%; 95% CI:

  11. Slide 11: Tebi Positioned As First Oral Carbapenem for cUTI

    Tebi Positioned As First Oral Carbapenem for cUTI Oral candidates for Complicated UTIs : Company Product Pharmacological Class Development Stage Spero Tebipenem HBr BL (Carbapenem) Phase 3 – stopped for efficacy Basilea Ceftibuten-ledaborbactam etzadroxil BL (cephalosporin)/BLI Phase 1 Shionogi/Qpex

  12. Slide 12: Out-Licensed to GSK for Regulatory Filings and Commercialization

    Out-Licensed to GSK for Regulatory Filings and Commercialization Global Collaboration (ex-Asia) Financial Terms Received $66 Million upfront and $9 Million in common stock investment Received $30 Million upon SPA agreement with the FDA SPRO granted GSK exclusive license to: Received $95 Million in d

  13. Slide 13: SPR720 Antibiotic for Non-Tuberculosis Mycobacterium Pulmonary Disease (NTM-PD)

    SPR720 Antibiotic for Non- Tuberculosis Mycobacterium Pulmonary Disease (NTM-PD) The company has suspended its current development for SPR720 13

  14. Slide 14: SPR720: Inhibits Gyrase B in Bacterial Cells

    SPR720: Inhibits Gyrase B in Bacterial Cells • Novel mechanism of action for NTM-PD not exploited by current antibiotics • No evidence of cross resistance against marketed antibiotics based on in vitro trials • Low propensity for development of resistance as monotherapy and in combination with SOC a

  15. Slide 15: Thank You

    THERAPEUTICS Thank You

  16. Slide 16: Clinical Experience Supports Safety, Efficacy of Tebipenem

    1 Clinical Experience Supports Safety, Efficacy of Tebipenem • 741 Adult subjects evaluated, across 17 efficacy and pharmacology trials Tebipenem Pivoxil evaluated in 23 • 440 pediatric subjects evaluated, across 6 efficacy and pharmacology trials trials enrolling over 1,300 • Generally well tolerat

  17. Slide 17: Activity of Tebipenem and Comparator Carbapenems against Uropathogens

    Activity of Tebipenem and Comparator Carbapenems against Gram-negative and - positive Uropathogens MIC (µg/mL) 90 Pathogen N Tebipenem Imipenem Meropenem Ertapenem Enterobacterales (Surveillance US & EU, 2022) E. coli 1,444 0.03≤0.12 0.03 0.015 K. pneumoniae 404 0.12 0.5 0.06 0.25 170 0.25 4 0.12 0.

  18. Slide 18: Tebipenem is Active Against Clinically Important Resistant Enterobacterales UTI Pathogens

    Tebipenem is Active Against Clinically Important Resistant Enterobacterales UTI Pathogens from Europe and the USA in 2022 MIC (µg/mL) 90 Organism/ Phenotype N phenotype Tebipenem Imipenem Meropenem Ertapenem Enterobacterales All 2,447 0.12 1 0.06 0.06 All 1,444 0.03≤0.12 0.03 0.015 ESBL* 205 0.03 0.

  19. Slide 19: Compound Structures and Definitions

    Compound Structures and Definitions Tebipenem Tebipenem Pivoxil Tebipenem Pivoxil Hydrobromide Active drug Orally bioavailable prodrug of Spero’s orally bioavailable prodrug + tebipenem (Orapenem® fine granules HBr salt, enabling high dosage and for pediatrics; Meiji Seika, Japan) room temperature-s

  20. Slide 20: Tebipenem Pharmacokinetic Profile

    Tebipenem Pharmacokinetic Profile • Prodrug rapidly converts to tebipenem in enterocytes of GI tract • Plasma Half-life ~1 hour • Dose-proportional PK relationship when administered fed or fasted state • Low potential for drug-drug interactions • No CYP450-dependent metabolism • No induction of CYP4

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