Here are 1-3 brief analogies for Spero Therapeutics (SPRO):

• They are like a specialized Vertex Pharmaceuticals, but intensely focused on developing new treatments for multi-drug resistant bacterial infections and specific rare lung diseases.
• Imagine an early-stage Gilead Sciences, concentrating on creating breakthrough drugs for the global crisis of antibiotic resistance rather than viral infections.

• Tebipenem HBr: An investigational oral antibiotic designed for complicated urinary tract infections caused by certain Gram-negative bacteria.
• SPR720: An investigational oral drug candidate for the treatment of non-tuberculous mycobacterial (NTM) lung disease.
• SPR206: An investigational intravenous drug candidate for multi-drug resistant Gram-negative infections, including hospital-acquired and ventilator-associated bacterial pneumonia.

Spero Therapeutics (SPRO) is a biopharmaceutical company focused on developing and commercializing novel treatments for multi-drug resistant bacterial infections. As such, it does not sell directly to individuals. Instead, Spero Therapeutics sells primarily to other companies, specifically other pharmaceutical companies through licensing agreements and, for its commercialized products, to pharmaceutical wholesalers.

The major customers and strategic partners for Spero Therapeutics are:

• Pfizer Inc. (NYSE: PFE): Spero has an exclusive license agreement with Pfizer for the commercialization of its lead product, XACERPAX (cefepime-taniborbactam), outside of the U.S. Pfizer also holds a right of first negotiation for XACERPAX in the U.S. This partnership involves upfront payments, potential milestone payments, and royalties on future sales.
• GSK plc (NYSE: GSK): Spero has a worldwide license agreement with GSK for its investigational oral antibiotic, tebipenem HBr. This agreement includes upfront and potential milestone payments, as well as royalties on future sales.

For its direct commercialization efforts of XACERPAX in the U.S., Spero's immediate customers are large pharmaceutical wholesalers and distributors (e.g., McKesson, Cardinal Health, AmerisourceBergen). These companies then distribute the drug to hospitals, clinics, and pharmacies. While these distributors are critical to market access, the strategic pharmaceutical partners (Pfizer and GSK) represent the most significant named "customer" relationships in terms of collaboration and direct revenue streams like license fees and milestones for a company at Spero's stage.

Esther Rajavelu, Interim President and Chief Executive Officer, Chief Financial Officer, and Chief Business Officer

Ms. Rajavelu has over two decades of experience in the life sciences sector, encompassing equities research, investment banking, and strategy consulting. She currently serves as Interim President and CEO, CFO, and CBO at Spero Therapeutics. Prior to joining Spero, she was the Chief Financial Officer at Fulcrum Therapeutics, a clinical-stage biopharmaceutical company. Her Wall Street career included roles as a senior equities research analyst covering SMID-cap biotechnology companies at UBS, Oppenheimer, and Deutsche Bank, and as a healthcare investment banker at Bank of America Merrill Lynch and EY Capital Advisors.

Timothy Keutzer, Chief Operating Officer

Mr. Keutzer has over 30 years of experience in the pharmaceutical industry across multiple functional and therapeutic areas. He previously served as Spero's Chief Development Officer. Before joining Spero, he was the Vice President of Program and Portfolio Management at Cubist Pharmaceuticals, where he was the program leader for ceftolozane/tazobactam, guiding it from Phase 1 to Phase 3 and its eventual approval in the US. His career also includes experience at Genetics Institute and Wyeth.

Ankit Mahadevia, MD, Co-founder and Board Member

Dr. Mahadevia is a co-founder of Spero Therapeutics and previously served as its President and CEO. He has co-founded nine therapeutics companies, including Spero Therapeutics itself, Synlogic (Nasdaq: SYBX), and Arteaus Therapeutics (acquired by Eli Lilly). He led three of these companies as Acting CEO, including Synlogic. Companies he was involved with, such as Arteaus Therapeutics (acquired by Lilly), Translate Bio (acquired by Sanofi), and Rodin Therapeutics (acquired by Alkermes), have been sold to acquirers. Prior to Spero, he was a Venture Partner in the life sciences group at Atlas Venture, an early-stage life sciences and technology venture capital firm.

John C. Pottage, Jr., M.D., Special Advisor to oversee medical function; Board Member and Chair of Development Committee

Dr. Pottage has over 20 years of experience in advancing therapeutics for infectious diseases. He currently serves as a Special Advisor to oversee Spero's medical function and is a member of its Board of Directors and Chair of the Development Committee. Prior to his current role, he was Senior Vice President and Head of the Infectious Disease Medicine Development Center at GSK (formerly GlaxoSmithKline). Before that, he served as Vice President of Global Clinical Development of Antivirals at GSK and held senior clinical development roles at Achillion Pharmaceuticals and Vertex Pharmaceuticals.

1. Discontinuation of the SPR720 Program: Spero Therapeutics has suspended the development of its SPR720 program for Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD). This decision followed an interim analysis of a Phase 2a study, which indicated that the drug did not meet its primary endpoint and raised potential dose-limiting safety concerns, including cases of reversible grade 3 hepatotoxicity. This discontinuation represents a significant setback for the company's pipeline diversification beyond its lead asset.
2. High Reliance on Tebipenem HBr and GSK Partnership: The future success and valuation of Spero Therapeutics are heavily dependent on the successful regulatory approval and commercialization of Tebipenem HBr for complicated urinary tract infections (cUTIs), as well as the ongoing partnership with GSK. While the Phase 3 PIVOT-PO trial for Tebipenem HBr met its primary endpoint and was stopped early for efficacy, the actual approval by the FDA (anticipated in mid-2026) and the subsequent commercial success and associated milestone and royalty payments are contingent on GSK's execution and market acceptance. GSK will assume all commercial responsibilities, meaning Spero will not bear these costs or risks directly but its financial upside is tied to this partnership's success.
3. Contingent Development of SPR206 and Limited Pipeline Beyond Tebipenem HBr: Beyond Tebipenem HBr, Spero's pipeline appears limited, with the advancement of SPR206, an investigational intravenously administered antibiotic, being contingent on securing non-dilutive funding. This reliance on external funding for further pipeline development highlights a risk to building a robust product portfolio if such funding is not secured, reinforcing concerns about an otherwise "empty pipeline" apart from the partnered asset.

Spero Therapeutics' primary product with a quantifiable addressable market is Tebipenem HBr.

• Tebipenem HBr: This investigational oral antibiotic is being developed for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis. The addressable market in the U.S. alone is estimated at $6 billion annually.
• SPR720: Null
• SPR206: Null

1. Commercialization and Royalty Revenue from Tebipenem HBr: The most significant driver of future revenue is the potential commercial launch and subsequent sales of Tebipenem HBr, an oral carbapenem antibiotic for complicated urinary tract infections (cUTI). Following positive Phase 3 trial results, Spero's partner, GSK, is expected to submit a New Drug Application (NDA) in the second half of 2025, with potential approval anticipated in mid-2026 in the U.S. and 2027 in the EU. GSK will be responsible for all commercial activities globally, excluding certain Asian territories. Spero is entitled to receive royalties on net product sales of Tebipenem HBr, with estimates suggesting blockbuster potential with annual sales exceeding one billion dollars.
2. Development and Sales Milestone Payments from GSK: Spero is eligible to receive substantial milestone payments from GSK under their licensing agreement. Approval of Tebipenem HBr is expected to trigger $175 million in milestone payments over the subsequent 12 months, with additional sales milestone payments totaling $225 million contingent upon commercialization and sales ramp. Spero has already received significant milestone payments, including a $23.8 million payment in August 2025, which contributes to its financial runway.
3. Grant Revenue: Spero Therapeutics expects to continue generating a portion of its revenue from payments under active government awards and any potential future awards. While collaboration revenue from the GSK partnership has recently increased, grant revenue has historically been a component of Spero's total revenue.

Share Issuance

• In January 2020, Spero Therapeutics announced a fully backstopped rights offering to raise $30.0 million, involving the potential issuance of up to 3,333,333 shares of common stock at $9.00 per share.
• In September 2020, the company priced a public offering of 4,785,000 shares of common stock and 3,215,000 shares of non-voting Series D Convertible Preferred Stock at $10.00 each, aiming for gross proceeds of $80.0 million.
• Pfizer Inc. made a $40 million equity investment in Spero Therapeutics in June 2021, purchasing 2,362,348 shares of common stock at $16.93 per share.

Inbound Investments

• In June 2021, Spero Therapeutics received a $40 million equity investment from Pfizer Inc. as part of the Pfizer Breakthrough Growth Initiative. The associated licensing agreement for SPR206 also made Spero eligible for up to $80 million in development and sales milestones, plus royalties.
• Spero entered into an exclusive license agreement with GSK in 2023 for tebipenem HBr, which included a $66.0 million upfront payment and eligibility for potential future development and commercial milestone payments (up to $101 million for commercial milestones after trial changes) and tiered royalties. GSK also purchased $9 million in Spero common stock as part of this deal.
• The company reported committed BARDA funding of $65.6 million as of August 2025, with $61.1 million of this recognized to date.

Capital Expenditures

• As of August 2025, Spero Therapeutics estimates that its existing cash and cash equivalents, combined with earned and non-contingent development milestone payments from GSK (including a $23.8 million payment received in August 2025), will be sufficient to fund its operating expenses and capital expenditures into 2028.
• In March 2025, the company had projected its cash runway to fund operating expenses and capital expenditures into Q2 2026.