Spero Therapeutics, Inc. (SPRO): Business Model Canvas [Dec-2025 Updated]

You're looking to cut through the noise and see exactly how Spero Therapeutics, Inc. (SPRO) plans to turn its late-stage antibiotic, tebipenem HBr, into a commercial success, and honestly, the model is razor-focused right now. As someone who's mapped these biotech plays for two decades, I can tell you this: the entire structure-from the $5.4 million in Q3 2025 collaboration revenue to the $48.6 million cash reserve on September 30, 2025-is built around the 4Q 2025 NDA submission to the FDA, heavily supported by the GSK license. It's a classic de-risked asset play, where the value proposition is a potential first oral carbapenem to cut hospital stays, but the risk is all tied to that single filing. Dig into the Canvas below to see the precise partnerships, costs, and revenue triggers that define Spero Therapeutics, Inc.'s near-term fate.

Spero Therapeutics, Inc. (SPRO) - Canvas Business Model: Key Partnerships

You're looking at the core alliances that power Spero Therapeutics, Inc.'s strategy as of late 2025. These deals are where the heavy lifting-and the cash flow-is happening, especially around tebipenem HBr.

GSK: Exclusive Global Commercialization Partner

The relationship with GSK centers on the late-stage asset, tebipenem HBr. Spero Therapeutics granted GSK an exclusive license to commercialize tebipenem HBr across all territories, with the exception of certain Asian territories retained by Meiji Seika Pharma Co. Ltd.

The pivotal PIVOT-PO Phase 3 trial concluded with an efficacy stop following a pre-specified interim analysis in Q2 2025, with results presented at IDWeek in October 2025. GSK plans to submit the data to the US Food and Drug Administration (FDA) in the fourth quarter of 2025, with a regulatory decision anticipated in the second half of 2026.

Financial interactions with GSK directly impact Spero Therapeutics, Inc.'s top line. For instance, total revenue in the second quarter of 2025 was $14.2 million, which was primarily due to collaboration revenue from GSK. However, total revenue for the third quarter of 2025 was $5.4 million, showing a decrease that was partly attributed to decreased collaboration revenue with GSK.

Key financial terms related to this partnership include:

• Final development milestone payment received from GSK in August 2025: $23.8 million.
• Maximum potential commercial milestone payments contingent upon first sales were adjusted to up to $101.0 million after the PIVOT-PO trial stopped early.
• GSK made a common stock investment of $9 million in Spero in Q4 2022, purchasing 7,450,000 shares at approximately $1.20805 per share.

Meiji Seika Pharma: Asian Territory Rights

Meiji Seika Pharma Co. Ltd. retains the development and commercialization rights for tebipenem HBr in Japan and certain other Asian countries. Meiji Seika Pharma has marketed the oral formulation, tebipenem pivoxil (as Orapenem), in Japan since 2009 for pediatric infections like pneumonia, otitis media, and sinusitis.

Clinical Research Organizations (CROs) and Academic/Scientific Collaborators

While Spero Therapeutics is responsible for the execution and costs of the PIVOT-PO Phase 3 trial, GSK is responsible for the execution and costs of planned regulatory filings and commercialization activities. The decrease in Research and Development expenses for the third quarter of 2025 to $8.6 million (down from $26.9 million in Q3 2024) was primarily due to reduced clinical expenses related to the PIVOT-PO Trial.

The table below summarizes the key financial impacts and status of the major external relationships as of late 2025:

Partner/Entity Type	Primary Role/Asset	Key Financial/Statistical Data (Latest Reported)
GSK	Exclusive global commercialization for tebipenem HBr (ex-Asia)	Final development milestone payment of $23.8 million received in August 2025.
Meiji Seika Pharma	Development/commercialization rights in certain Asian territories	Marketed tebipenem pivoxil in Japan since 2009.
GSK Collaboration Revenue	Tebipenem HBr development support	Contributed to Q2 2025 revenue of $14.2 million.
Government Agencies (BARDA/HHS)	Funding support for antibiotic development (historical/ongoing)	SPR206 program discontinued in Q1 2025; historical funding for SPR994 reached up to $54.2 million commitment.
Internal Cash Runway	Overall financial planning	Cash and cash equivalents of $48.6 million as of September 30, 2025, funding operations into 2028.

Government Agencies: Funding Support

Government funding has played a role in pipeline support, though grant revenue has fluctuated. Grant revenue decreased in the first quarter of 2025, contributing to lower total revenue of $5.9 million compared to $9.3 million in Q1 2024. Similarly, grant revenue decreased in Q3 2025.

Historically, federal agencies provided significant support:

• Biomedical Advanced Research and Development Authority (BARDA) funding for SPR994 (tebipenem) included an initial $15.7 million, with provisions for up to an additional $28.5 million over five years.
• Total federal agencies committed up to $54.2 million for the SPR994 project as of 2018.
• Select tebipenem HBr studies were partially funded by DHHS/ASPR/BARDA under contract number HHSO100201800015C.

Spero Therapeutics discontinued the SPR206 program in the first quarter of 2025, noting gratitude to government agencies that helped finance that program.

Spero Therapeutics, Inc. (SPRO) - Canvas Business Model: Key Activities

You're managing a company right at the inflection point of a major regulatory submission, so the key activities are laser-focused on execution and partnership support. Here's the breakdown of what Spero Therapeutics, Inc. is driving right now.

Regulatory Filing: Preparing and submitting the tebipenem HBr NDA to the FDA in 4Q 2025

The primary activity here is enabling the New Drug Application (NDA) submission for tebipenem HBr. Spero's development partner, GSK, plans to submit the data package to the US Food and Drug Administration (FDA) in the 4Q 2025 timeframe. This follows the successful presentation of the Phase 3 PIVOT-PO trial results at IDWeek in October 2025. The drug already benefits from both Qualified Infectious Disease Product (QIDP) and Fast Track designations from the FDA, which should help streamline the review process. Honestly, the focus is on timely handover to GSK for this critical filing.

The anticipated regulatory decision date, should the filing be accepted, is set for the 2H 2026 period.

Clinical Data Analysis: Completing analysis of the positive PIVOT-PO Phase 3 trial results

The analysis of the PIVOT-PO trial is essentially complete, as the results were presented in October 2025. The trial was stopped early for efficacy back in May 2025 following an Independent Data Monitoring Committee (IDMC) review of 1,690 enrolled patients. The core finding was meeting the primary endpoint of non-inferiority against intravenous imipenem-cilastatin.

Here are the key statistical outcomes from that analysis:

Metric	Tebipenem HBr (Oral)	Imipenem-Cilastatin (IV)
Overall Success Rate	58.5% (261/446 participants)	60.2% (291/483 participants)
Adjusted Treatment Difference	-1.3%	N/A
95% Confidence Interval (CI)	-7.5% to 4.8%	N/A
Clinical Cure Rate	93.5%	95.2%

This activity directly impacted operating costs; Research and development expenses for the third quarter of 2025 were $8.6 million, a significant drop from $26.9 million in the same period of 2024, largely because clinical expenses related to PIVOT-PO were reduced. That's the quick math on cost savings from stopping the trial early.

Pipeline Management: Strategic review and discontinuation of non-core programs like SPR720 (Q3 2025)

Spero Therapeutics made a sharp strategic pivot, which is a tough but necessary activity for resource concentration. The company officially discontinued the SPR720 program in Q3 2025 after reviewing data from its Phase 2a and Phase 1 trials for NTM-PD. To be fair, this followed the earlier discontinuation of the SPR206 program in Q1 2025 during a pipeline reprioritization. This streamlining resulted in a workforce reduction of approximately 39%. The goal of this restructuring was to ensure the company's existing cash and cash equivalents, reported at $48.6 million as of September 30, 2025, will fund operations into 2028.

The focus is now clearly on tebipenem HBr and supporting the GSK collaboration.

Intellectual Property Management: Maintaining and expanding patent protection for tebipenem HBr

Intellectual Property (IP) management centers on the exclusive license agreement with GSK. Spero Therapeutics granted GSK worldwide rights to commercialize tebipenem HBr, except for certain Asian territories retained by Spero's partner, Meiji Seika Pharma Co. Ltd. Spero itself holds the rights and responsibility for development work, including the PIVOT-PO study, after which NDA sponsorship transfers to GSK. This structure means Spero is actively managing its sub-licensing rights under the Meiji agreement while relying on GSK for global commercial IP defense post-launch. We don't have specific IP maintenance dollar figures, but the structure itself is a key activity.

Partner Collaboration: Supporting GSK's pre-commercialization and global development efforts

This is a massive operational component, as GSK is driving the commercialization efforts. Spero's key activity is supporting GSK's pre-commercialization work leading up to the 4Q 2025 filing. Financially, this partnership is critical for Spero's runway. Spero received a $23.8 million final development milestone payment from GSK in August 2025. However, collaboration revenue fluctuates; Total revenue for Q3 2025 was $5.4 million, down from $13.5 million in Q3 2024, primarily due to decreased collaboration revenue with GSK. Still, the potential upside is substantial.

The financial structure of the collaboration includes:

• Initial upfront payment received from GSK: $66 million.
• Potential milestone payments remaining: up to $400 million.
• Contingent commercial milestone payments (adjusted): up to $101.0 million.
• Tiered royalties on net product sales: in the low single to double digits.

If approved, tebipenem HBr could address an estimated $6 billion per year in US healthcare costs associated with cUTIs, which is the market GSK will target. Finance: draft 13-week cash view by Friday.

Spero Therapeutics, Inc. (SPRO) - Canvas Business Model: Key Resources

You're looking at the core assets Spero Therapeutics, Inc. is relying on right now to push tebipenem HBr toward a potential approval. These aren't just ideas; they are hard numbers and legal agreements that define the company's current operational capacity.

Tebipenem HBr: Late-stage oral carbapenem antibiotic asset with QIDP/Fast Track status

The key asset is tebipenem HBr, an investigational oral carbapenem antibiotic for complicated urinary tract infections (cUTI), including pyelonephritis. The pivotal Phase 3 PIVOT-PO trial was stopped early for efficacy in May 2025. Results presented at IDWeek in October 2025 showed non-inferiority against the intravenous standard of care. The asset carries Qualified Infectious Disease Product (QIDP) and Fast Track designations from the FDA, which are critical regulatory advantages.

Here's a look at the key efficacy data from the PIVOT-PO trial:

Metric	Tebipenem HBr (Oral 600 mg)	Imipenem-Cilastatin (IV 500 mg)
Participants Evaluated	446	483
Overall Success Rate	58.5% (261/446)	60.2% (291/483)
Adjusted Treatment Difference (95% CI)	1.3% (-7.5%, 4.8%)

Intellectual Property: Patents and regulatory exclusivity protecting the tebipenem HBr formulation

The value here is tied directly to the regulatory pathway. The QIDP designation grants ten years of market exclusivity upon approval, independent of patent life, which is a significant barrier to entry for competitors. The Fast Track status helps expedite the FDA review process, which is crucial for near-term revenue potential.

Cash Reserves: $48.6 million in cash and equivalents as of September 30, 2025

Financially, Spero Therapeutics, Inc. is operating with a defined runway. As of the end of the third quarter of 2025, the balance sheet held $48.6 million in cash and cash equivalents. This figure, combined with noncontingent milestone receipts, is projected to fund the company's operating expenses and capital expenditures well into 2028. The net loss for Q3 2025 was $7.4 million.

GSK License Agreement: Provides funding, development expertise, and global commercial infrastructure

The partnership with GSK is a major resource, providing validation and commercial muscle. GSK is responsible for the planned FDA submission in Q4 2025, with an anticipated regulatory decision in 2H 2026. Spero Therapeutics, Inc. received a final development milestone payment of $23.8 million from GSK in August 2025. Following the early trial stop, the aggregate potential commercial milestone payments contingent upon first sales were adjusted down from up to $150.0 million to up to $101.0 million.

• Exclusive commercialization rights for GSK in all territories, except certain Asian territories.
• Meiji holds development and commercialization rights in certain Asian territories.
• Total potential commercial milestones: up to $101.0 million.
• Final development milestone received in August 2025: $23.8 million.

Specialized Personnel: Small team of R&D and regulatory experts focused on anti-infectives

The human capital is lean and highly focused. The team is centered on executing the final steps for the tebipenem HBr submission and managing the partnership obligations. Esther Rajavelu took on the role of President and Chief Executive Officer in May 2025, also maintaining the CFO and Treasurer roles, indicating a tight operational structure.

The team's focus areas include:

• Regulatory interaction for the planned Q4 2025 New Drug Application (NDA) submission.
• Managing the ongoing relationship with GSK for commercial planning.
• Internal financial oversight to maintain the runway into 2028.

Finance: draft 13-week cash view by Friday.

Spero Therapeutics, Inc. (SPRO) - Canvas Business Model: Value Propositions

You're looking at the core reasons why Spero Therapeutics, Inc. (SPRO)'s lead asset, tebipenem HBr, is so compelling to the market right now, especially following the late 2025 data readouts. This isn't just about a new drug; it's about changing the standard of care for serious infections.

Oral Carbapenem: Potential first oral carbapenem in the US for cUTI/pyelonephritis

The primary value is the mechanism: tebipenem HBr successfully demonstrated non-inferiority to the intravenous (IV) standard-of-care, imipenem-cilastatin, in the Phase 3 PIVOT-PO trial for complicated urinary tract infections (cUTI). This positions tebipenem HBr to potentially become the first oral carbapenem approved in the US. The trial involved around 1,690 adult patients. The company plans to submit the New Drug Application (NDA) to the FDA in the second half of 2025.

This asset is the linchpin of Spero Therapeutics, Inc. (SPRO)'s current valuation, with peak sales estimates for tebipenem HBr exceeding $500 million and a total market potential cited around $2.5 billion. If the NDA is submitted in H2 2025, Spero is entitled to receive a milestone payment of $25 million.

Reduced Hospitalization and Cost Savings

Shifting from IV to oral therapy for a significant portion of treatment directly impacts healthcare economics. An oral carbapenem offers a clear path to reducing the length of time patients need acute care. While Spero Therapeutics, Inc. (SPRO)'s specific reduction in hospitalization days isn't quantified in the trial data, the general principle holds: oral antibiotics for severe infections are associated with significant cost savings compared to IV therapy. For instance, one retrospective study noted that patients treated with an alternative non-intravenous regimen had a shorter hospital stay [median (IQR) 7 (5-10) days vs. 12 (9-18) days for the carbapenem group]. The cost-effectiveness of moving to an oral option is a major driver for formulary adoption.

Here's a quick look at the comparative profile based on clinical data points:

Attribute	IV Standard of Care (Imipenem-cilastatin)	Oral Candidate (Tebipenem HBr)
Route of Administration	Intravenous (IV)	Oral Tablet
cUTI Trial Endpoint	Comparator Arm	Met non-inferiority to IV
Potential Hospital Stay Impact	Associated with longer median stay (e.g., 12 days in one comparator study)	Potential to shorten hospital stays by allowing outpatient completion
Regulatory Status (Late 2025)	Established	NDA submission planned for H2 2025

Combatting Resistance

The value proposition is amplified by the critical need for new agents against resistant bacteria. Spero Therapeutics, Inc. (SPRO) is focused on novel treatments for multi-drug resistant (MDR) bacterial infections. Carbapenems are often reserved for serious infections caused by pathogens that resist other antibiotics, so offering an oral option preserves the activity of other agents while providing a potent oral treatment for susceptible MDR strains.

Patient Convenience

The ability to complete treatment at home is a huge quality-of-life improvement. This means fewer clinic visits or home health nursing requirements for IV infusions. The value here is tangible patient benefit, which translates to better adherence and outcomes.

The convenience allows for at-home treatment completion, improving patient quality of life.

The company's financial health supports this focus, with Q2 2025 results showing a reduced net loss of $1.7 million and a cash position of $31.2 million, extending the cash runway into 2028, contingent on milestone payments.

• Potential peak sales estimates: $500 million.
• Total potential milestone payments from GSK: up to $400 million.
• Cash runway extends into 2028.

Finance: draft 13-week cash view by Friday.

Spero Therapeutics, Inc. (SPRO) - Canvas Business Model: Customer Relationships

You're looking at the relationships Spero Therapeutics, Inc. maintains to drive its late-stage asset forward, which is key for any pre-commercial biotech. These aren't just polite exchanges; they are contractual obligations and critical dependencies.

Strategic Partner Management: High-touch, collaborative relationship with GSK for co-development and regulatory support

The relationship with GSK, the exclusive commercialization partner for tebipenem HBr outside of certain Asian territories, dictates much of Spero Therapeutics' near-term activity. This partnership is financially significant; Spero received an upfront payment of $66 million back at the initial agreement in 2022, and more recently, a final development milestone payment of $23.8 million in August 2025, on top of a $23.75 million non-contingent payment earlier that quarter. Collaboration revenue from GSK was $14.2 million in the second quarter of 2025, though it decreased in the third quarter of 2025, contributing to a total Q3 2025 revenue of $5.4 million. The structure of future upside is also defined here, with Spero entitled to up to $225 million in additional sales milestone payments plus tiered royalties on net product sales.

Here's a quick look at the commercial milestone potential tied to this relationship:

Sales Threshold	Potential Milestone Payment
Exceeds $200 million	$25 million
Exceeds $500 million	$50 million
Exceeds $1,000 million	$50 million

The PIVOT-PO trial stopping early reduced the aggregate potential commercial milestone payments contingent upon first sales from up to $150.0 million to up to $101.0 million. Still, GSK assumes all commercial responsibilities post-approval, meaning Spero Therapeutics avoids post-launch costs and risks.

Regulatory Body Engagement: Direct, formal communication with the FDA for NDA submission and review

The primary focus of regulatory engagement is the New Drug Application (NDA) for tebipenem HBr. Spero Therapeutics, working with GSK, plans to submit the data package from the Phase 3 PIVOT-PO trial to the US Food and Drug Administration (FDA) in the 4Q 2025. This submission is bolstered by the drug's existing designations: Qualified Infectious Disease Product (QIDP) and Fast Track. Following the submission, Spero anticipates a regulatory decision in the 2H 2026. This formal, data-driven dialogue is the gate to market access.

Key Opinion Leader (KOL) Relations: Presenting clinical data at major scientific conferences (e.g., IDWeek 2025)

Engaging the infectious disease community through data presentation is crucial for establishing the value proposition of tebipenem HBr. Spero Therapeutics presented the Phase 3 PIVOT-PO results at the IDWeek 2025 annual meeting, which took place in Atlanta, Georgia, between October 19 - 22, 2025. The late-breaking oral presentation occurred on Monday October 20, 2025, from 1:45 PM - 3:00 PM Eastern Time. Two supporting poster presentations followed on Tuesday 21 October, from 12:15 to 1:30 pm. These presentations showcased the trial met its primary endpoint of non-inferiority versus intravenous imipenem-cilastatin.

Key data points shared with KOLs included:

• Phase 3 PIVOT-PO trial met primary endpoint of non-inferiority.
• Oral tebipenem HBr compared to intravenous imipenem-cilastatin.
• Most frequent adverse events were diarrhea and headache (in 3% of patients).
• Trial stopped early after 1,690 patients were enrolled.

Investor Relations: Transparent updates on clinical milestones and cash runway (into 2028)

You, as an investor, need clear visibility on the company's financial sustainability. As of the end of the third quarter, September 30, 2025, Spero Therapeutics reported cash and cash equivalents of $48.6 million. Management projects that this existing cash, combined with other expected funds, will be sufficient to fund operating expenses and capital expenditures into 2028. This runway extends well past the anticipated regulatory decision date in 2H 2026, providing significant operational breathing room. For context, the net loss for Q3 2025 was $7.4 million, an improvement from the $17.1 million loss reported in Q3 2024.

Clinical Site Support: Managing relationships with investigators and hospitals for trial execution

The successful completion of the PIVOT-PO trial relied on managing relationships with clinical investigators and the hospitals they represent. The trial was stopped early following a pre-specified interim analysis. This early stop was based on data from 1,690 patients enrolled. The original plan required full enrollment of 2,637 patients to trigger the maximum potential milestone payment of $150.0 million, so the early termination altered the financial relationship with GSK but validated the clinical execution by the sites.

Spero Therapeutics, Inc. (SPRO) - Canvas Business Model: Channels

You're looking at how Spero Therapeutics, Inc. (SPRO) gets its value proposition-a potential first-in-class oral carbapenem for complicated urinary tract infections (cUTIs)-to the customer. For Spero Therapeutics, Inc., the channels are heavily weighted toward its strategic partner, GSK, for the post-approval phase, but Spero Therapeutics, Inc. maintains critical internal channels for data dissemination and investor relations right up to the expected New Drug Application (NDA) transfer.

GSK's Global Commercial Infrastructure: Primary channel for market access, sales, and distribution post-approval

The primary commercial channel for tebipenem HBr, if approved, rests with GSK. Spero Therapeutics, Inc. granted GSK an exclusive license to commercialize tebipenem HBr in all territories, excluding specific Asian territories retained by Meiji Seika. This structure means GSK leverages its established global commercial reach for market access and distribution, which is a huge advantage given the high unmet medical need. Spero Therapeutics, Inc. is set to receive tiered royalties on net product sales, ranging from low-single digit to low-double digit if sales exceed $1 billion.

Here's a look at the financial relationship that underpins this channel:

Financial Metric/Event	Value/Date	Context
Upfront Payment from GSK (2022)	$66 million	Initial payment for exclusive license rights.
GSK Stock Investment	$9 million	Shares purchased at approximately $1.20805 per share.
Final Development Milestone Received (August 2025)	$23.8 million	Earned upon PIVOT-PO success and prior to NDA submission.
Adjusted Max Potential Commercial Milestones	Up to $101.0 million	Adjusted from $150.0 million after the trial stopped early for efficacy.

This partnership defines the post-approval channel strategy. Honestly, Spero Therapeutics, Inc. relies on GSK's expertise for the heavy lifting of global launch.

Regulatory Submissions: FDA and other global health authorities for market authorization

The regulatory pathway is a critical, near-term channel to market. GSK, as the responsible party for regulatory filings, plans to submit data from the PIVOT-PO trial to the US Food and Drug Administration (FDA) as part of a planned filing in 4Q 2025. Spero Therapeutics, Inc. is supporting GSK in preparing this filing. The PIVOT-PO study itself was covered by a Special Protocol Assessment (SPA) agreement entered into with the FDA in 2023. Following the submission, Spero Therapeutics, Inc. currently anticipates an FDA regulatory decision in 2H 2026.

Key regulatory milestones leading to this point include:

• Phase 3 PIVOT-PO trial stopped early for efficacy in May 2025.
• Primary endpoint met: non-inferiority to IV imipenem-cilastatin.
• Trial involved 1,690 patients.
• FDA designations received: Qualified Infectious Disease Product (QIDP) and Fast Track.

Scientific Publications/Conferences: Disseminating clinical data to infectious disease specialists and prescribers

Before the NDA submission, disseminating positive clinical data is essential to build awareness among key prescribers-infectious disease specialists. Spero Therapeutics, Inc. and GSK presented the results from the Phase 3 PIVOT-PO trial as a late-breaker oral abstract session at IDWeek 2025 in October 2025. This is a prime channel for establishing the clinical profile of tebipenem HBr. The data showed an overall success rate of 58.5% for oral tebipenem HBr versus 60.2% for IV imipenem-cilastatin, with an adjusted difference of -1.3%, falling within the non-inferiority margin.

The internal development team's focus has shifted following program decisions:

• Discontinued the SPR720 program in Q3 2025.
• Discontinued the SPR206 program following a pipeline review.

This focus sharpens the scientific communication channel directly onto tebipenem HBr.

Investor Communications: Press releases and SEC filings (Form 10-Q) for financial and business updates

For the financial community, Spero Therapeutics, Inc. uses formal filings and press releases as a direct channel to communicate operational status. For example, the Third Quarter 2025 Operating Results were announced on November 13, 2025. These communications detail the cash position and runway, which are key for analysts modeling future financing needs.

Here are the latest figures from the Q3 2025 update:

Financial Metric	Value/Date	Source
Market Capitalization (as of Nov 13, 2025)	$128.45M
Total Revenue (Q3 2025)	$5.4 million
Cash and Cash Equivalents (as of Sep 30, 2025)	$48.6 million
Estimated Cash Runway	Into 2028

The decrease in R&D expenses for Q3 2025 to $8.6 million (down from $26.9 million in Q3 2024) reflects the completion of the PIVOT-PO trial execution.

Direct Development Team: Spero's internal team manages the final development work before NDA transfer

While GSK handles commercialization, Spero Therapeutics, Inc.'s internal team managed the execution and costs of the Phase 3 PIVOT-PO trial. This internal capability is the bridge channel that ensures the data package is ready for transfer to GSK for the NDA submission. The team's work on the PIVOT-PO trial was a major focus, which, upon early stopping, resulted in meaningful cost savings in the near term. The team's direct efforts culminated in the successful data readout and presentation, setting up the final regulatory push.

Finance: draft 13-week cash view by Friday.

Spero Therapeutics, Inc. (SPRO) - Canvas Business Model: Customer Segments

You're looking at the core groups Spero Therapeutics, Inc. (SPRO) targets with its lead asset, tebipenem HBr, based on late 2025 operational data. This is all about who benefits from, pays for, or partners on the drug.

Global Pharmaceutical Companies: This segment is dominated by the partnership with GlaxoSmithKline (GSK). GSK is the entity seeking late-stage, de-risked antibiotic assets to bolster its infectious disease portfolio. Spero Therapeutics is entitled to significant future value from this relationship, which is structured around commercialization outside of specific Asian territories. GSK is responsible for the execution and costs of additional clinical development, including regulatory submission and commercialization activities in their licensed regions.

The financial structure tied to this partnership is key to Spero Therapeutics' near-term outlook. As of the third quarter of 2025, Spero Therapeutics expected its current cash and cash equivalents to fund operations into 2028. This runway is supported by the successful Phase 3 trial and expected milestone receipts from GSK.

Hospitalized cUTI Patients: These are the adults with complicated urinary tract infections, including pyelonephritis, who are the direct recipients of the potential therapy. The need is substantial, as an estimated 2.9 million cases of cUTIs are treated annually in the US. Tebipenem HBr is designed to be an effective oral therapeutic taken outside a hospital setting, offering an alternative to intravenous (IV) carbapenem therapies. The Phase 3 PIVOT-PO trial confirmed non-inferiority to the IV standard, imipenem-cilastatin, based on an overall success rate of 58.5% for tebipenem HBr versus 60.2% for the IV comparator.

Infectious Disease Specialists: These are the prescribing physicians who face the challenge of treating serious, often multi-drug resistant, infections. They are the gatekeepers for adopting a new oral step-down therapy like tebipenem HBr. The drug's potential to provide an oral option after initial IV treatment could significantly impact their prescribing patterns for cUTI management.

Payers/Hospitals: This segment is focused on the economic impact of treatment duration and route of administration. Hospitalized cUTIs contribute to over $6 billion per year in US healthcare costs. The value proposition here is reducing hospital resource utilization and shortening hospital stays by allowing for an earlier, effective oral step-down from IV therapy. Spero Therapeutics' partner, GSK, plans to submit data to the US Food and Drug Administration (FDA) in the fourth quarter of 2025, with an anticipated regulatory decision in the second half of 2026.

Here's a quick look at the financial context for Spero Therapeutics as of the end of Q3 2025, which underpins their ability to support this customer segment strategy:

Metric	Value (as of Q3 2025 or related event)
Cash and Cash Equivalents (Sep 30, 2025)	$48.6 million
Estimated Cash Runway	Into 2028
Net Loss (Q3 2025)	$7.4 million
Total Revenue (Q3 2025)	$5.4 million
Total US cUTI Cases Treated Annually	2.9 million
Estimated US cUTI Healthcare Costs Annually	Over $6 billion

Asian Markets: This segment involves the territories where Spero Therapeutics' original partner, Meiji Seika Pharma Co. Ltd., retains development and commercialization rights. Spero Therapeutics granted GSK an exclusive license for all territories except Japan and certain other Asian countries retained by Meiji Seika. This means Meiji Seika is the direct customer segment contact in these specific Asian territories.

The potential upside for Spero Therapeutics from the GSK deal, which covers markets outside of Meiji Seika's, includes significant future payments:

• Total potential milestone payments: up to $400 million.
• Tiered royalties on net product sales: in the low single to double digits (if sales exceed $1bn).

Finance: draft 13-week cash view by Friday.

Spero Therapeutics, Inc. (SPRO) - Canvas Business Model: Cost Structure

When you look at Spero Therapeutics, Inc. (SPRO)'s cost structure as of late 2025, you see a company heavily weighted toward its clinical and discovery efforts, though costs are shifting due to recent program decisions. The primary spending categories reflect the biopharma reality: getting a drug from the lab to the market.

Research & Development (R&D) Expenses

Research & Development is definitely the main cost driver here. For the third quarter of 2025, Spero Therapeutics reported R&D expenses totaling $8.6 million. This is a significant drop from the $26.9 million reported in the third quarter of 2024. The reason for this reduction is key: it reflects lower spending on clinical activities and the discontinuation of a program.

• R&D Expenses (Q3 2025): $8.6 million
• R&D Expenses (Q3 2024): $26.9 million
• Primary driver for decrease: Reduced clinical expenses and SPR720 program wind-down.

Clinical Trial Costs

The PIVOT-PO trial, which evaluated tebipenem HBr for complicated urinary tract infection (cUTI), was a major cost component that has now largely been contained. The trial was stopped early for efficacy in May 2025 following a pre-specified interim analysis with 1,690 patients enrolled, which reduced Spero's overall costs for that study. The data analysis for this trial is a current focus, as Spero is working with GSK to enable an FDA filing in Q4 2025. The early stoppage also impacted potential future payments under the collaboration agreement.

Here's how the PIVOT-PO trial stoppage adjusted the financial structure related to that development:

Metric	Original Potential Value	Adjusted Potential Value (Post-Early Stop)
Maximum Potential Milestone Payment (Contingent on Full Enrollment)	Up to $150.0 million	Up to $101.0 million
Total Potential Milestone Payments (All Contingencies)	Up to $525 million (as of late 2022)	Up to $400 million (as of mid-2025)

General & Administrative (G&A) Expenses

Corporate overhead, which covers things like executive salaries, legal, and general office expenses, came in at $4.2 million for the third quarter of 2025. This is down from $5.2 million in the same period last year. Honestly, that reduction points to effective cost management, primarily driven by lower personnel-related costs.

• G&A Expenses (Q3 2025): $4.2 million
• Primary reason for decrease: Lower personnel-related costs.

Licensing/Collaboration Costs

While the primary financial interaction with the GSK collaboration is revenue-based (milestone payments and royalties), Spero initially bore the costs for the Phase 3 PIVOT-PO trial execution. The structure is now largely cost-neutral for future commercialization, as GSK assumes responsibility for the regulatory filing and commercialization activities outside of the retained Asian territories. The agreement entitles Spero to significant future consideration, including royalties in the low single to double digits on net product sales, plus sales milestone payments up to $225 million.

Intellectual Property Costs

Specific, recurring line items for Intellectual Property (IP) costs, like patent maintenance fees or new filings, aren't explicitly broken out in the public Q3 2025 summary figures. However, the value of Spero's IP is intrinsically tied to the exclusive license agreement with GSK for tebipenem HBr. Maintaining the patent portfolio is a necessary, ongoing cost within the overall R&D or G&A structure to protect the assets that underpin the collaboration and future royalty streams. The company's cash position as of September 30, 2025, was $48.6 million, which they estimate is sufficient to fund operating expenses into 2028.

Finance: draft 13-week cash view by Friday.

Spero Therapeutics, Inc. (SPRO) - Canvas Business Model: Revenue Streams

You're looking at the core income drivers for Spero Therapeutics, Inc. as of late 2025. Honestly, the story here is almost entirely about the partnership with GlaxoSmithKline (GSK) on tebipenem HBr. Everything else is either historical or a future possibility contingent on regulatory success.

Collaboration Revenue

The primary, recurring revenue stream right now is the collaboration revenue from the GSK license agreement. This isn't product sales yet, but payments tied to the development progress of tebipenem HBr. For the third quarter of 2025, this collaboration revenue totaled $5.4 million. To give you some context on the variability, the collaboration revenue in the preceding quarter, Q2 2025, was reported at $11.802 million. This fluctuation is typical as development activities ebb and flow, but it remains the main source of operational cash flow outside of the balance sheet.

Milestone Payments

Milestone payments are the lumpy, but significant, cash injections that validate the science and de-risk the balance sheet. You saw a major one hit in August 2025: Spero Therapeutics received a non-contingent development payment of $23.8 million from GSK. That payment was the final development milestone under the GSK License Agreement, and management noted that this, combined with existing cash, extends the runway into 2028.

The remaining potential is now weighted toward commercial success, but the structure is important to map out. Here's a quick look at the key remaining contingent milestones tied to the GSK deal, keeping in mind that the first commercial sales trigger was recently adjusted:

Milestone Event Category	Contingent Amount (Up To)	Source of Data
Contingent on First Commercial Sales	$101.0 million
Net Sales Milestones (Post-First Sale)	Up to $250 million (based on remaining tiers)
Total Potential Remaining (Excluding Royalties)	Approximately $351 million

Future Commercial Milestones

The big money is tied to the market performance of the drug post-approval. Specifically, the potential payment contingent on the very first commercial sales is up to $101.0 million. This figure was adjusted following the early stop of the PIVOT-PO trial, which reduced the maximum potential payment tied to that initial sales trigger because the trial did not continue to full enrollment. Still, securing that first commercial milestone is a massive step for Spero Therapeutics.

Tiered Royalties

Once GSK launches tebipenem HBr, Spero Therapeutics becomes entitled to tiered royalties on net product sales. The structure is designed to reward early success with higher rates. You should expect these royalties to start in the low double digits and then step down to the low single digits once certain annual net sales thresholds are met. This provides a long-tail revenue stream that scales directly with the drug's market adoption.

Grant Revenue

Grant revenue, which historically provided non-dilutive funding for R&D from government agencies, is definitely a decreasing source of income for Spero Therapeutics. The Q3 2025 total revenue of $5.4 million reflected a decrease due to lower collaboration revenue and decreased grant revenue compared to the prior year. This trend aligns with the company's strategic decision to cease development of the SPR720 program and focus resources entirely on the GSK-partnered asset.

You'll want Finance to track the Q4 2025 revenue closely to see if the final development milestone payment in August was enough to offset the drop in recurring collaboration and grant income.