SPRO

Image source: The Motley Fool. Wednesday, Aug. 12, 2026 at 5:00 p.m. ET President and Chief Executive Officer - Esther Rajavelu Chief Medical Officer - Debra Zack Head of Investor Relations - Shai Biran Need a quote from a Motley Fool analyst? Email [email protected] Operator: Good afternoon, and welcome to the Spero Therapeutics Second Quarter 2026 Earnings Conference Call. Please be advised that this call is being recorded, and a replay will be available. You can find the information on the replay and further information related to today's announcement on the Spero Therapeutics website at sperotx.com. At this time, I would like to turn the call over to Shai Biran, Head of Investor Relations. Mr. Biran, please go ahead. Shai Biran: Thank you, operator, and thank you all for participating in today's conference call. This afternoon, Spero Therapeutics released financial results and provided a business update for the second quarter of 2026. A press release is available on the Investor page of the Spero Therapeutics website. Before we begin, I would like to remind you that some of the information presented on this conference call contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as amended. These forward-looking statements are based on Spero's current expectations and assumptions and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties associated with our business and factors that could cause or contribute to such differences are described in Spero's filings with the Securities and Exchange Commission, including in the Risk Factors section of the earnings report on Form 10-Q for the quarter ended June 30, 2026, filed today. Leading the call today are Esther Rajavelu, our President and Chief Executive Officer; and Dr. Debra Zack, our Chief Medical Officer. There will be a Q&A session following the prepared remarks. I will now turn the call over to Esther to begin. Esther Rajavelu: Thank you, Shai. Good afternoon, everyone, and thank you for joining us on our second quarter earnings and business update call. I will begin with key highlights from the quarter, outline our strategy and priorities going forward and then review our financial results. In the last 90 days, we had 4 major milestones. The FDA approved Utebzi, the first and only oral carbapenem for the treatment of complicated urinary tract infections, including pyelonephritis, which we developed with our licensing partner, GSK. We in-licensed SP001 and repositioned the company's pipeline to focus on immune-mediated diseases. We closed $105 million nondilutive, nonrecourse financing, and we hired a Chief Medical Officer. Let me start with the last one by welcoming Dr. Debra Zack to the Spero team as our CMO. Deb is a Board-certified rheumatologist with a PhD in immunology and extensive drug development experience spanning research, clinical development and medical affairs. She brings more than 25 years of leadership in developing therapeutics for immune-mediated diseases, most recently as CMO at Exagen and before that in clinical leadership roles at Amgen, Xencor and Novartis. She officially joined Spero as CMO on August 3 to lead our clinical development strategy as we advance SP001 into the clinic. Deb Welcome. We are so glad you're here and look forward to your comments on SP001 later during this call. Let me now turn to the quarter. On June 17, the FDA approved Utebzi or tebipenem pivoxil infections, including pyelonephritis caused by certain susceptible pathogens in patients who have limited or no alternative oral treatments. It is the first and only oral carbapenem antibiotic approved in the United States. The approval was based on PIVOT-PO, the Phase III study we ran under our license agreement with GSK. The study was stopped early for efficacy in May 2025. GSK holds exclusive commercialization rights worldwide, excluding certain Asian territories where Meiji retains rights. GSK expects Utebzi to be available to U.S. patients in the second half of this year. Following more than a decade of commitment and work by the Spero team to progress this asset through the clinic, Utebzi's approval provided the company an opportunity to pursue other growth prospects in immunological diseases with high unmet medical need, which brings me to our announcements in July. On July 8, we announced an exclusive license agreement with Innovent Biologics for SP001, also known as IBI355 for an estimated $1.1 billion in total contingent deal value. Separately, on July 8, we also announced $105 million nondilutive, nonrecourse royalty financing with affiliates of Healthcare Royalty, a business of KKR. Let me begin with our newly in-licensed asset, SP001. Our agreement with Innovent provides us with exclusive worldwide rights, excluding Greater China, to develop and commercialize SP001 for all indications. Innovent retains rights in Greater China. SP001 is a third-generation fully humanized Fc silent IgG1 monoclonal antibody targeting CD40 ligand. In the clinic, SP001 completed 2 Phase I studies in healthy volunteers, including a single ascending dose and a multiple ascending dose study as well as a Phase Ib multiple ascending dose study in primary Sjogren's disease. Data from the Sjogren's disease trial were presented in a poster at the EULAR Congress in June this year. We intend to advance SP001 in immunoglobulin G4-related disease or IgG4-RD with a Phase II trial expected to begin in the second quarter of 2027. In parallel, we will also evaluate additional development opportunities to potentially expand the SP001 value proposition. Dr. Zack will cover details on the drug, the CD40 ligand mechanism and our development plan in IgG4-RD. Moving on to our financing. We closed $105 million nondilutive nonrecourse royalty financing with Healthcare Royalty. The structure of the financing, which is also discussed in our 10-Q filed today and our 8-K filed on July 8 is as follows: A special purpose subsidiary issued $105 million in senior secured notes. The notes carry a 10% annual interest rate and a 9-year maturity. Principal and interest are payable quarterly and are derived solely from the milestone and royalty payments GSK owes us on Utebzi. After the notes are repaid, Spero retains 35% of additional GSK milestone and royalty proceeds. Let me take a moment to emphasize that the notes are nonrecourse to Spero and our other assets are not exposed to Utebzi launch or sales risk. This transaction further strengthened our balance sheet and provided non-dilutive capital as we embark on an immunology-focused strategy. By unlocking immediate value from a portion of future Utebzi milestone and royalty streams, we are well positioned to execute on the clinical development for SP001. Following the transaction, we updated our cash runway guidance into the second half of 2029. Spero was founded with the strategy of in-licensing promising clinical stage assets and with an experienced and focused team advancing those programs through clinical development to commercialization. Following these transactions, we believe we continue to be well positioned to execute on our business strategy. I will now turn the call over to Deb to provide an overview of SP001, CD40 ligand as a target and our development plan for IgG4-RD. Debra Zack: Thank you, Esther. I'm thrilled to join the Spero team as CMO, and I look forward to working together to bring this important candidate to patients. I will begin today with an overview of the asset, SP001, then I will share our preliminary development plans for IgG4-RD, subject to future discussions with the FDA. SP001 is a third-generation fully humanized Fc silent IgG1 monoclonal antibody targeting CD40 ligand. Let me explain why this target and this molecule are attractive opportunities for clinical development. CD40 ligand is an upstream immune activation signal. It sits at the interface of adaptive and innate immunity, orchestrating the interactions between T cell, B cell and antigen-presenting cells. Blocking CD40 ligand interrupts a critical activation signal. Patients with immune-mediated diseases could experience meaningfully different therapeutic benefits by inhibiting CD40 ligand because we would be modulating the conversation between immune cells before they become pathogenic. The biology of this pathway has been well studied for over 2 decades and therapeutic targeting has been clinically validated. T cells talk to B cells and macrophages using the same molecule, the CD40 ligand, which serves as a go signal. The antigen-presenting cell, which is the immune system's alarm, gets the signal and acts to release more inflammatory cytokines, survive longer and continue to support the T cells. The B cell gets the signal and acts to proliferate, switch antibody class and produce more antibodies, including IgG4. We believe this mechanism has the potential to modulate multiple components of the disease process simultaneously, which is why this target could be attractive across multiple autoimmune indications and not just one. We will advance SP001 first in IgG4-related disease with a Phase II trial expected to begin in the second quarter of 2027. IgG4-related disease is a serious chronic fibroinflammatory disease that can affect nearly every organ system, including the pancreas, kidneys, salivary and tear glands, the aorta, lungs, even the lining of the brain. Patients are typically 50 to 70 years old. Over time, that inflammation causes scarring and fibrosis and if left undertreated, it can progress to organ failure. A successful treatment should aim to reduce flares and treat the underlying course of disease. There are an estimated 20,000 to 40,000 diagnosed patients in the U.S., and we believe diagnosis rates should increase as a disease-specific diagnostic code was just implemented 2.5 years ago in October of 2023. Treatment guidelines are being revised, which we believe will broaden the addressable market. IgG4-RD is defined by B cells and the antibodies they make. But B cells don't act alone in this disease, the disease burden can also be attributed to T cells and macrophages along with the B cells, all creating inflammatory and profibrotic signals. Targeting CD40 ligand, which sits upstream of all of these could theoretically turn down several sources of pathology at once, including antibody production, antigen presentation and potentially fibrotic signals. Currently, diagnosed patients are monitored until the disease flares. And at that point, one of a few off-label options such as steroids with or without disease-modifying antirheumatic drugs are used to control the flare for most patients. If the flare remains uncontrolled, then patients often progress to B-cell depleters such as off-label rituximab and the recently approved Uplizna. The result is that these patients continue on a cycle of remission and relapse as the depleted B cells repopulate over time, and there's no option at the present time for durable long-term disease control for these patients. The current development landscape for IgG4-RD, where all the other biologic agents either deplete or inhibit B cells only leaves room for an additional mechanism to enter development. We believe that CD40 ligand inhibition may offer a differentiated approach relative to therapies that target B cells alone by disrupting the pathologic interaction between T cells and the B cells that contribute to disease activity. We believe it is important to target the B/T cell co-stimulation process in IgG4-RD because it can potentially help to stop the fibroinflammatory process from worsening while also controlling flares more consistently. Our planned Phase II trial is aimed at establishing proof of concept in IgG4-RD. We anticipate running an open-label trial with 6 monthly dosing in 2 dosing arms, enrolling up to 15 patients in each arm. I will now turn the call back to Esther to review the quarterly financials. Esther Rajavelu: Thank you, Deb. Let me now review Spero's financial results for the second quarter ended June 30, 2026. As of June 30, the company had cash and cash equivalents of $50.8 million. This balance does not reflect the net proceeds from the royalty financing we completed in July 2026. We expect that our cash and cash equivalents at June 30, together with the proceeds of the royalty financing will be sufficient to fund the $35 million nonrefundable upfront payment to Innovent and our operating expenses and capital expenditures into the second half of 2029. There was no revenue for the second quarter of 2026 compared with total revenue of $14.2 million for the second quarter of 2025. The change compared with the prior year period was primarily due to the collaboration revenue from Pfizer and GSK being fully realized in prior periods and all funding having been received under the government awards. Research and development expenses for the second quarter of 2026 were $3.4 million compared to $10.7 million for the same period in 2025. The decrease in R&D expenses year-over-year was primarily due to reduced clinical activity following the early completion of the Phase III trial for Utebzi in the first half of 2025, together with lower personnel-related costs. G&A expenses for the second quarter of 2026 were $6.5 million compared to $5.9 million for the same period in 2025. The increase was primarily due to increases in business development, legal and consulting expenses. The company reported a net loss of $9.6 million for the second quarter of 2026 compared with a net loss of $1.7 million for the second quarter of 2025. Diluted net loss per share was $0.16 and $0.03 for the second quarters of 2026 and 2025, respectively. For further details on our financials, please refer to our 10-Q filed with the SEC today. With that, I will turn it back to the operator for Q&A. Operator: [Operator Instructions] Our first question today is from Ram Selvaraju with H.C. Wainwright. Raghuram Selvaraju: Congratulations on all of the recent progress. Progress made on many fronts, I might add. I was wondering if I could ask Deb to perhaps elaborate on the following 3 aspects as it pertains to the envisioned clinical program. How are you thinking about specifically assessing the magnitude and significance of clinical benefit? And in particular, how does this dovetail with the way in which you envision the product ultimately being positioned as and when it might get to market in IgG4-RD? Is this, for example, with respect to flare suppression, symptom control, achievement of long-term remission and/or reduction in use of steroidal therapy or DMARDs or something else or some combination of all of these factors? And then I was hoping you could also elaborate on the structural features of this molecule and why that might point to its potentially being best-in-class in the CD40 ligand category. Debra Zack: Thank you so much for this question. Let me start with your second question first, the structural features of this particular molecule. There are several other molecules, which are in the CD40 ligand type arena. Two of those are fusion proteins, whereas the other 3 are very -- are quite similar to the SP001, we think that the particular features of SP001 that we have seen in preclinical and other suggest that it might have some additional or a bit of better control -- interaction with the molecule, forgive me. But the PK of the antibody itself and the fact that it's very specific are key features, making a monoclonal antibody molecule very, very attractive for use in this area. When you talk about the Phase II trial, magnitude and clinical benefit for IgG4 relates to how we think about this impacting the upstream nature rather than just affecting the B cells, also going towards inhibiting that crosstalk between T cells, innate immunity and the B cells. In the trial itself, in the Phase II trial itself, we will be looking for symptom control and also for control over the period of time as well as reduction in steroids and DMARD use. The way that the Phase III trials are done are quite opposite. The flare suppression, we're looking to establish rather than that we're inhibiting recurrent flares, although we will see that in 6 months. But what we're really looking for is that the molecule controls the symptoms and has a good safety profile and that we can take away the other steroids that are detrimental to patients often in this age group and with these disease and concomitant features. Phase III would be where we would look at the flare suppression because there, you do the opposite, you control the disease and then put your agent on and see that the flares do not resume. Does that answer your question? Or are there further features? Raghuram Selvaraju: Yes. No, that's very, very helpful. And I understand that there's a lot that cannot be definitively answered at this specific point. I also wanted to touch upon 2 other aspects. One of these pertains to the way in which a drug like this might be deployed in IgG4-RD given the current armamentarium. In other words, would you anticipate that it could be seamlessly inserted into the existing toolbox, so to speak, and potentially deployed alongside or as an adjunct to therapy with B-cell depleters as a replacement for B-cell depleters and perhaps most importantly, how it might play alongside a drug like Uplizna. And then just maybe Esther, you and Esther could comment on this aspect. If we look at the commercial opportunity, how has the commercial experience with Uplizna to whatever extent you have information on market uptake and so on since the label was extended into IgG4-RD inform how you're thinking about the magnitude of the commercial opportunity here? Esther Rajavelu: Thanks, Ram. Maybe I'll take the first stab at least the last part of your question, which is on the commercial opportunity here with IgG4 and then Deb can cover some of the other positioning questions that you asked. So we can't comment on Uplizna uptake, but what I will share is that this disease is fairly early in its life cycle. It was only defined just about a couple of decades ago, and the patient communities are just coming together and even rheumatologists who treat this disease are still getting their arms around understanding the patient profiles as well as the treatment regimens that are available, both on -- both as approved agents as well as off-label use of some of the other therapies that Deb walked you through in the prior question. We do expect to see diagnosis rates improving in this disease increasing, especially because there was a diagnostic code that was established just a couple of years ago. And as we've seen with other rare diseases, when the patient communities come together and there are approved therapies that are available and prescribers are awareness increases, you do see a much higher uptake and increasing diagnosis rate. So that's our expectation over the next several years for this market commercially. Let me turn it over to Deb to answer your other question. Debra Zack: Yes. You wanted to know how this would fit with other things that are in use. The ones that are currently in use are B-cell ablators and steroids, both of which have -- work well, but have potential downsides for this age group, especially with comorbidities present. The other piece that's a little bit different is that what currently happens is that patients are treated when they flare, they're brought down under control, they go off medication and then it's a waiting game until the disease comes back. So I can see where a molecule such as this by continuing control of the disease, you smooth out that treatment regimen so that the patient continues to be under control, thereby not adding to the damage that may already be there and progressing to further damage. It could certainly be used after one of the other agents in order to control following that because the disease is pretty relentless and coming back even if once controlled. We tend not to cure things in rheumatology, but we do try to control them very well. Operator: [Operator Instructions] Showing no further questions, this concludes our question-and-answer session. I would like to turn the conference back to Esther Rajavelu for any closing remarks. Esther Rajavelu: Thanks, operator. To close, Spero has entered an exciting new chapter as an immunology company. We move forward with a focus on immune-mediated diseases anchored by our lead asset, SP001 and a strengthened balance sheet. These provide us with cash runway into the second half of 2029. We look forward to keeping you updated on our progress in the quarters ahead. Thank you all again for joining us today and for your continued interest in Spero. This concludes our call. Operator: The conference has now concluded. Thank you for attending today's presentation. You may now disconnect. Before you buy stock in Spero Therapeutics, consider this: The Motley Fool Stock Advisor analyst team just identified what they believe are the 10 best stocks for investors to buy now… and Spero Therapeutics wasn’t one of them. The 10 stocks that made the cut could produce monster returns in the coming years. Consider when Netflix made this list on December 17, 2004... if you invested $1,000 at the time of our recommendation, you’d have $419,408!* Or when Nvidia made this list on April 15, 2005... if you invested $1,000 at the time of our recommendation, you’d have $1,348,694!* Now, it’s worth noting Stock Advisor’s total average return is 966% — a market-crushing outperformance compared to 213% for the S&P 500. Don't miss the latest top 10 list, available with Stock Advisor, and join an investing community built by individual investors for individual investors. See the 10 stocks » *Stock Advisor returns as of August 19, 2026. This article is a transcript of this conference call produced for The Motley Fool. While we strive for our Foolish Best, there may be errors, omissions, or inaccuracies in this transcript. As with all our articles, The Motley Fool does not assume any responsibility for your use of this content, and we strongly encourage you to do your own research, including listening to the call yourself and reading the company's SEC filings. Please see our Terms and Conditions for additional details, including our Obligatory Capitalized Disclaimers of Liability. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy. Spero Therapeutics (SPRO) Q2 2026 Earnings Call Transcript was originally published by The Motley Fool

This article first appeared on GuruFocus. Cash and Cash Equivalents: $50.8 million as of June 30, 2026, excluding net proceeds from the July 2026 royalty financing. Revenue: No revenue for Q2 2026, compared to $14.2 million in Q2 2025, primarily due to prior collaboration revenue from Pfizer and GSK being fully realized. R&D Expenses: $3.4 million in Q2 2026, down from $10.7 million in Q2 2025, due to reduced clinical activity following the early completion of the Utebzi Phase 3 trial. G&A Expenses: $6.5 million in Q2 2026, up from $5.9 million in Q2 2025, driven by higher business development, legal, and consulting costs. Net Loss: $9.6 million for Q2 2026, compared to a net loss of $1.7 million in Q2 2025. Diluted Net Loss Per Share: $0.16 for Q2 2026, versus $0.03 in Q2 2025. Cash Runway Guidance: Updated to fund operations into the second half of 2029, including the $35 million nonrefundable upfront payment to Innovent. Warning! GuruFocus has detected 4 Warning Signs with SPRO. Is SPRO fairly valued? Test your thesis with our free DCF calculator. Release Date: August 12, 2026 For the complete transcript of the earnings call, please refer to the full earnings call transcript. FDA approval of Utebzi, the first oral carbapenem antibiotic, provides a significant commercial milestone and potential revenue stream through GSK partnership. In-licensing of SP001, a third-generation anti-CD40L antibody, diversifies pipeline into high-unmet-need immunology, with potential across multiple autoimmune indications. Closed $105 million non-dilutive, non-recourse royalty financing, strengthening balance sheet and extending cash runway into the second half of 2029. Appointment of Dr. Debra Zack as CMO brings deep immunology expertise, enhancing clinical development capabilities for SP001. SP001's mechanism targeting CD40L offers a differentiated approach by modulating upstream immune activation, potentially addressing multiple disease pathways in IgG4-RD. No revenue recorded in Q2 2026, down from $14.2 million in Q2 2025, due to completion of prior collaboration agreements. Net loss widened to $9.6 million in Q2 2026 from $1.7 million in Q2 2025, reflecting increased expenses and lack of revenue. SP001 is still in early clinical stages, with Phase 2 trial not expected to begin until Q2 2027, indicating a long path to potential commercialization. The royalty financing carries a 10% annual interest rate and nine-year maturity, with payments derived solely from Utebzi milestones/royalties, which may be uncertain. Dependence on GSK's successful launch and sales of Utebzi for future royalty income, which is subject to market and regulatory risks. Q: How are you thinking about assessing the magnitude and significance of clinical benefit in the planned Phase 2 trial for SP001 in IgG4-RD, and how does this align with the product's potential market positioning? Additionally, what structural features of the molecule suggest it could be best-in-class in the CD40 ligand category?A: Dr. Debra Zack (CMO): For the Phase 2 trial, we will focus on symptom control, disease control over time, and reduction in steroid and DMARD use, rather than flare suppression, which is typically reserved for Phase 3 trials. The structural features of SP001, being a fully humanized, Fc-silent IgG1 monoclonal antibody, offer a very specific interaction with the target and favorable pharmacokinetics compared to other molecules in the CD40 ligand space, which are often fusion proteins. This specificity makes it a very attractive candidate. Q: How might SP001 be deployed in the current treatment landscape for IgG4-RD, and how does the commercial experience with Uplizna inform your view of the market opportunity?A: Esther Rajavelu (CEO): We cannot comment on Uplizna's uptake, but the IgG4-RD market is early in its life cycle. Diagnosis rates are expected to improve, especially with the new diagnostic code established in October 2023. As patient communities and prescriber awareness grow, we anticipate a higher uptake and increasing diagnosis rates, similar to other rare diseases. Dr. Zack added that SP001 could be used to maintain disease control, smoothing out the current cycle of flares and remissions, and could be used after other agents like B-cell depleters to provide sustained control. Q: Can you elaborate on the key highlights and strategic milestones for Spero in the second quarter of 2026?A: Esther Rajavelu (CEO): We achieved four major milestones: the FDA approved Utebzi, the first oral carbapenem for complicated UTIs; we in-licensed SP001 and repositioned the pipeline toward immune-mediated diseases; we closed a $105 million non-dilutive, non-recourse royalty financing; and we hired Dr. Debra Zack as our Chief Medical Officer. These events have strengthened our balance sheet and positioned us to execute on our new immunology-focused strategy. Q: What is the significance of the FDA approval of Utebzi, and what are the next steps for commercialization?A: Esther Rajavelu (CEO): The FDA approved Utebzi on June 17, 2026, for complicated urinary tract infections, including pyelonephritis. It is the first and only oral carbapenem approved in the US. GSK holds exclusive commercialization rights worldwide (excluding certain Asian territories) and expects Utebzi to be available to US patients in the second half of 2026. This approval provides Spero with the opportunity to pursue growth in immunological diseases. Q: Can you provide details on the $105 million royalty financing and its impact on the company's cash runway?A: Esther Rajavelu (CEO): We closed a $105 million non-dilutive, non-recourse royalty financing with Healthcare Royalty. The notes carry a 10% annual interest rate and a nine-year maturity, with payments derived solely from GSK's milestone and royalty payments on Utebzi. After the notes are repaid, Spero retains 35% of additional proceeds. This transaction strengthens our balance sheet and extends our cash runway into the second half of 2029, providing capital to fund SP001's clinical development. Q: What is the rationale for targeting CD40 ligand with SP001, and why is this mechanism attractive for immune-mediated diseases?A: Dr. Debra Zack (CMO): CD40 ligand is an upstream immune activation signal at the interface of adaptive and innate immunity. Blocking it interrupts a critical activation signal, modulating the conversation between T cells, B cells, and antigen-presenting cells before they become pathogenic. This mechanism has the potential to modulate multiple components of the disease process simultaneously, making it attractive across multiple autoimmune indications, not just IgG4-RD. Q: What is the current treatment landscape for IgG4-RD, and where does SP001 fit in?A: Dr. Debra Zack (CMO): IgG4-RD is a serious, chronic fibroinflammatory disease affecting nearly every organ system. Currently, patients are monitored until flares, then treated with off-label options like steroids or DMARDs. If uncontrolled, they may progress to B-cell depleters like rituximab or Uplizna. This creates a cycle of remission and relapse. SP001, by targeting CD40 ligand upstream, could disrupt the pathologic interaction between T cells and B cells, potentially stopping the fibroinflammatory process and providing more consistent disease control. Q: What are the financial results for the second quarter of 2026?A: Esther Rajavelu (CEO): As of June 30, 2026, the company had cash and cash equivalents of $50.8 million, which does not reflect the July royalty financing proceeds. There was no revenue for Q2 2026, compared to $14.2 million in Q2 2025, due to prior collaboration revenue being fully realized. R&D expenses decreased to $3.4 million from $10.7 million, primarily due to reduced clinical activity. G&A expenses increased to $6.5 million from $5.9 million. The net loss was $9.6 million, or $0.16 per share, compared to a net loss of $1.7 million, or $0.03 per share, in the prior year period. For the complete transcript of the earnings call, please refer to the full earnings call transcript.

Interested in Spero Therapeutics, Inc.? Here are five stocks we like better. Utebzi was approved by the FDA for certain complicated urinary tract infections, with GSK expected to launch the first U.S. oral carbapenem in the second half of 2026. Spero also secured $105 million in non-recourse royalty financing tied to future Utebzi payments, extending funding into the second half of 2029. Spero is shifting toward immunology through its exclusive license for SP001, a CD40 ligand antibody with up to $1.1 billion in potential deal value. The company plans to begin a Phase II trial in IgG4-related disease in the second quarter of 2027. Second-quarter revenue fell to zero and net loss widened to $9.6 million, or $0.16 per diluted share, from $1.7 million a year earlier. Spero ended the quarter with $50.8 million in cash, excluding the July financing proceeds. Spero Therapeutics (NASDAQ:SPRO) used its second-quarter update to outline a strategic shift toward immune-mediated diseases, supported by the FDA approval of Utebzi and a new licensing agreement for SP001, an antibody candidate the company plans to develop initially for IgG4-related disease. President and Chief Executive Officer Esther Rajavelu said the company reached four major milestones during the past 90 days: FDA approval of Utebzi, the in-licensing of SP001, completion of a $105 million royalty financing arrangement, and the appointment of Dr. Debra Jeske Zack as chief medical officer. → SoundHound AI Sends a Loud Signal After Its Q2 Earnings Beat The company reported no revenue for the second quarter of 2026 and a net loss of $9.6 million, or $0.16 per diluted share. Spero ended the quarter with $50.8 million in cash and cash equivalents, excluding proceeds from the financing completed in July. On June 17, the FDA approved Utebzi, or tebipenem HBr, for the treatment of complicated urinary tract infections, including pyelonephritis, caused by certain susceptible pathogens in patients with limited or no alternative oral treatment options. Rajavelu described Utebzi as the first and only oral carbapenem antibiotic approved in the United States. → AST SpaceMobile Earnings Just Reminded Investors How Risky Space Can Be The approval was based on the Phase III PIVOT-PO study, which was stopped early for efficacy in May 2025. GSK holds exclusive worldwide commercialization rights for the drug outside certain Asian territories retained by Meiji. GSK expects Utebzi to become available to U.S. patients during the second half of 2026, according to Rajavelu. Spero subsequently closed a $105 million non-dilutive, non-recourse royalty financing with affiliates of HealthCare Royalty Partners, a business of KKR. A special-purpose subsidiary issued senior secured notes with a 10% annual interest rate and a nine-year maturity. Principal and interest payments will be funded solely by milestone and royalty payments that GSK owes Spero related to Utebzi. → First Solar’s Profit Engine Faces a New Policy Test in Washington After the notes are repaid, Spero will retain 35% of additional GSK milestone and royalty proceeds. Rajavelu said the financing is non-recourse to Spero and does not expose the company’s other assets to Utebzi launch or sales risks. Management said its June 30 cash balance, together with proceeds from the financing, is expected to fund the $35 million non-refundable upfront payment to Innovent Biologics as well as operating expenses and capital expenditures into the second half of 2029. On July 8, Spero announced an exclusive license agreement with Innovent Biologics for SP001, also known as IBI355, with an estimated $1.1 billion in total contingent deal value. The agreement gives Spero worldwide development and commercialization rights outside Greater China, where Innovent retains rights. SP001 is a third-generation, fully humanized Fc-silent IgG1 monoclonal antibody targeting CD40 ligand. The candidate has completed Phase I single-ascending-dose and multiple-ascending-dose studies in healthy volunteers, as well as a Phase Ib multiple-ascending-dose study in patients with primary Sjögren’s disease. Data from the Sjögren’s trial were presented at the EULAR Congress in June. Zack, who joined Spero on Aug. 3, said CD40 ligand is an upstream immune activation signal involved in interactions among T cells, B cells and antigen-presenting cells. She said blocking the pathway could potentially affect several components of immune-mediated disease, including antibody production, antigen presentation and inflammatory signaling. Spero intends to advance SP001 first in IgG4-related disease, or IgG4-RD, with a Phase II trial expected to begin in the second quarter of 2027. The company also plans to evaluate additional development opportunities for the asset. IgG4-RD is a chronic fibroinflammatory disease that can affect multiple organ systems, including the pancreas, kidneys, salivary and tear glands, aorta and lungs. Zack said untreated or undertreated inflammation can lead to scarring, fibrosis and potentially organ failure. Spero estimates there are 20,000 to 40,000 diagnosed patients in the United States. Management expects diagnosis rates to increase following the implementation of a disease-specific diagnostic code in October 2023 and anticipated updates to treatment guidelines. Zack said current treatment can include steroids, disease-modifying antirheumatic drugs, off-label rituximab and recently approved Uplizna. She said patients commonly cycle through remission and relapse as B cells repopulate over time, and that no option currently provides durable long-term disease control. The planned Phase II trial is expected to be open label, with dosing every six months and two dose arms enrolling up to 15 patients each. Zack said the study is intended to establish proof of concept and will assess symptom control, disease control over time, safety, and potential reductions in steroid and disease-modifying drug use. “What we are really looking for is that the molecule controls the symptoms and has a good safety profile,” Zack said, adding that the company aims to determine whether other treatments, including steroids, can be reduced. Second-quarter 2026 revenue was zero, compared with $14.2 million in the second quarter of 2025. Research and development expense fell to $3.4 million from $10.7 million a year earlier, primarily reflecting reduced clinical activity after Utebzi’s Phase III study concluded early and lower personnel costs. General and administrative expense increased to $6.5 million from $5.9 million, driven by higher business development, legal and consulting costs. Net loss was $9.6 million, compared with a $1.7 million net loss in the prior-year period. Diluted net loss per share was $0.16, compared with $0.03 a year earlier. Rajavelu said Spero is now moving forward as an immunology-focused company, with SP001 as its lead asset and funding expected to support the company through the second half of 2029. Spero Therapeutics is a clinical‐stage biopharmaceutical company focused on the discovery and development of novel therapies to address multidrug‐resistant bacterial infections. Headquartered in Boston, Massachusetts, the company aims to advance a pipeline of oral and intravenous antibiotic candidates designed to treat serious infectious diseases that pose significant public health challenges. The company's lead candidate, tebipenem HBr, is an oral carbapenem antibiotic being developed for the treatment of complicated urinary tract infections caused by resistant Gram‐negative pathogens. This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to [email protected]. The article "Spero Therapeutics Q2 Earnings Call Highlights" was originally published by MarketBeat. View MarketBeat's top stocks for August 2026.

Our analysts just identified a stock with the potential to be the next Nvidia. Tell us how you invest and we'll show you why it's our #1 pick. Tap here. Transitioned the corporate focus to immune-mediated diseases following the FDA approval of Utebzi, the first oral carbapenem for complicated urinary tract infections. In-licensed SP001, a third-generation fully humanized Fc silent IgG1 monoclonal antibody targeting CD40 ligand, to serve as the new lead clinical asset. Secured $105 million in non-dilutive, non-recourse royalty financing from Healthcare Royalty to fund the immunology pipeline without exposing core assets to Utebzi commercial risk. Appointed Dr. Debra Zack as Chief Medical Officer to leverage her 25 years of experience in rheumatology and immunology for the development of SP001. Attributed the year-over-year revenue decline to the full realization of collaboration revenue from Pfizer and GSK and the completion of government award funding. Reduced R&D expenses significantly due to the early completion of the Utebzi Phase III trial and associated lower personnel-related costs. Positioned the company with a cash runway extending into the second half of 2029, covering the $35 million upfront payment for SP001 and future clinical operations. Plans to initiate a Phase II trial for SP001 in IgG4-related disease (IgG4-RD) in the second quarter of 2027, focusing on establishing proof of concept. Anticipates increased diagnosis rates for IgG4-RD driven by the implementation of a specific diagnostic code in October 2023 and evolving treatment guidelines. Expects GSK to make Utebzi available to U.S. patients in the second half of 2026, which will trigger the milestone and royalty streams used to service the new debt. Intends to evaluate additional development opportunities for SP001 beyond IgG4-RD to expand the asset's value proposition across multiple autoimmune indications. Assumes a clinical strategy for IgG4-RD that aims to disrupt the pathologic interaction between T cells and B cells to stop fibroinflammatory progression. The $105 million royalty financing is structured as senior secured notes with a 10% interest rate, payable solely from Utebzi-related proceeds from GSK. Spero retains 35% of Utebzi milestone and royalty proceeds after the notes are fully repaid, preserving long-term upside from the antibiotic asset. Management highlighted that the financing is non-recourse, meaning Spero's other assets and cash are protected regardless of Utebzi's commercial performance. Identified the current IgG4-RD landscape as having high unmet need, as existing off-label treatments often lead to a cycle of remission and relapse. One stock. Nvidia-level potential. 30M+ investors trust Moby to find it first. Get the pick. Tap here. Management stated that SP001's specific PK profile and monoclonal antibody structure offer potentially better control and specificity compared to fusion protein competitors. The Phase II trial will prioritize symptom control and reduction in steroid/DMARD use, while flare suppression will be the primary focus of a subsequent Phase III trial. The mechanism targets the 'crosstalk' between T cells and B cells, aiming to modulate the immune response before it becomes pathogenic. Management envisions SP001 as a way to 'smooth out' treatment regimens by providing durable long-term control, unlike current B-cell depleters that allow disease return upon repopulation. The drug could potentially be used as an adjunct or follow-up to existing therapies to prevent the relentless return of fibroinflammatory damage. The company expects the market to expand as rheumatologists become more aware of the disease and patient communities coalesce around new approved therapies.

Entered an exclusive license agreement with Innovent Biologics for SP001, a Phase 2-ready, third-generation anti-CD40L antibody for immune-mediated diseases U.S. Food and Drug Administration approved Utebzi™ (tebipenem pivoxil), the first and only oral carbapenem antibiotic for adults with complicated urinary tract infections (cUTIs), including pyelonephritis Closed $105 million non-recourse, non-dilutive financing backed by a portion of future Utebzi milestones and royalties, extending cash runway into the second half of 2029 Appointed Debra Zack, M.D., Ph.D., as Chief Medical Officer Conference call today at 5pm EDT CAMBRIDGE, Mass., Aug. 12, 2026 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc. (Nasdaq: SPRO), a clinical-stage biopharmaceutical company focused on advancing next-generation medicines in immunology and inflammation, today announced financial results for the second quarter ended June 30, 2026, and provided a corporate update. "During the second quarter, we achieved several defining milestones that have fundamentally strengthened Spero's business. We entered the quarter as a company preparing for an important regulatory milestone and have since then announced the FDA approval of Utebzi; a new Phase 2-ready immunology program with SP001; and financing that positions us to continue executing on our mission to deliver transformative therapies to patients,” said Esther Rajavelu, President and Chief Executive Officer of Spero. "As we look to the remainder of 2026, our priorities are to advance SP001 toward a Phase 2 study in IgG4-related disease and continue evaluating additional development opportunities in immune-mediated diseases to expand the SP001 value proposition, while maintaining our disciplined approach to execution.” Recent Business Highlights Exclusive License Agreement with Innovent Biologics for SP001 In July 2026, Spero entered into an exclusive license agreement with Innovent Biologics, Inc. for SP001. Spero gained exclusive rights to develop, research, manufacture, and commercialize SP001 worldwide, excluding Greater China (Mainland China, Hong Kong, Macau, and Taiwan), where Innovent retains rights. SP001 is a third-generation, fully humanized, Fc-silent IgG1 monoclonal antibody targeting CD40L, an upstream immune activation signal involved in T-cell, B-cell, antigen-presenting cell, and platelet biology. Innovent completed two healthy volunteer Phase 1 trials, a single ascending dose (“SAD”) study and a multiple ascending dose (“MAD”) study, as well as a Phase 1b MAD study in patients with primary Sjögren’s disease (“SjD”). Data from the Phase 1b SjD study were presented in a poster session at the EULAR 2026 Congress. Spero plans to advance SP001 into a Phase 2 study in IgG4-related disease (IgG4-RD), a serious, rare chronic fibroinflammatory disease with significant treatment burden and limited therapeutic options. Utebzi (tebipenem pivoxil) U.S. FDA Approval In June 2026, Spero and GSK announced that the U.S. Food and Drug Administration (FDA) approved Utebzi for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, caused by certain susceptible pathogens in adult patients who have limited or no alternative oral treatment options. Utebzi is the first and only oral carbapenem antibiotic approved for these patients. The product is expected to be made available by GSK to U.S. patients by the end of 2026. GSK holds commercialization rights in the U.S. and Europe. $105 Million Non-Recourse, Non-Dilutive Royalty Financing In July 2026, Spero announced a non-recourse, non-dilutive royalty financing with affiliates of HealthCare Royalty Partners, a business of KKR (HCRx), for $105 million in gross proceeds, in exchange for rights to a portion of the anticipated payments from sales of Utebzi owing from GSK (GSK Proceeds). The transaction is structured as a non-recourse Note Purchase and Guaranty Agreement (NPA) generally payable solely from the GSK proceeds, and a Royalty and Milestone Payment Interest Purchase and Sale Agreement (RPA) under which the Company may retain 35% interest in the GSK Proceeds arising after required payments under the NPA, preserving potential long-term upside from the asset. The proceeds will primarily support advancement of SP001. Corporate In July 2026, Spero announced the appointment of Debra Jeske Zack, M.D., Ph.D., as Chief Medical Officer. Dr. Zack is a board-certified rheumatologist with a Ph.D. in immunology and brings more than 25 years of leadership in developing therapeutics for immune-mediated diseases. She will oversee Spero's clinical development strategy and organization as the Company advances its immunology program. Second Quarter 2026 Financial Results Spero reported a net loss of $9.6 million for the second quarter of 2026 compared to a net loss of $1.7 million for the second quarter of 2025, or a diluted net loss per share of common stock of $0.16 and $0.03, respectively. No revenue was recognized for the second quarter of 2026, compared to total revenue of $14.2 million for the second quarter of 2025, as all deferred revenue under the collaboration agreements was recognized in prior periods and all grant revenue has been fully recognized, and the awards have been completed and closed out. Research and development expenses for the second quarter of 2026 were $3.4 million, compared to $10.7 million of research and development expenses for the same period in 2025. The decrease in research and development expenses was a result of decreased clinical activities related to our pivotal Phase 3 clinical trial of Utebzi, which was stopped early for efficacy in the first half of 2025, and a decrease in personnel related costs. General and administrative expenses for the second quarter of 2026 were $6.5 million, compared to $5.9 million of general and administrative expenses for the same period in 2025. The increase was a result of increased legal and business development costs, offset partially by a decrease in personnel related costs. As of June 30, 2026, cash and cash equivalents were $50.8 million. This balance does not reflect the proceeds from the royalty financing completed in July 2026. The company expects that its cash and cash equivalents at June 30, 2026, together with the proceeds of the royalty financing, will be sufficient to fund operating expenses and capital expenditure into the second half of 2029. For further details on Spero’s financials, refer to Spero’s Quarterly Report on Form 10-Q, filed with the U.S. Securities and Exchange Commission (SEC) today. Conference call and webcast Management will host a conference call and live audio webcast at 5:00 pm EDT today, August 12, to discuss the results and provide a business and pipeline update. To access the call, please dial 1-877-407-0789 (domestic) or 1-201-689-8562 (international) and refer to conference ID 13762082, or click on this link to request a return call. The webcast for the event can be accessed live on this link, or on the Investor Relations page of the Spero Corporate website at https://www.sperotx.com/. The archived webcast will be available for 30 days following the call. About SP001 SP001 is a third-generation, potential best-in-class, fully humanized, Fc-silent IgG1 monoclonal antibody targeting CD40L, an upstream immune activation signal involved in T-cell, B-cell, antigen-presenting cell, and platelet biology. By blocking CD40L, SP001 has the potential to provide a targeted non-B-cell-depleting treatment across multiple immune-mediated diseases where immune-cell interactions drive chronic inflammation, relapse, and tissue damage. SP001 is designed to address platelet activation concerns associated with earlier anti-CD40L antibodies, while preserving key monoclonal antibody properties, including FcRn interaction that supports IgG-like half-life. About Spero Therapeutics Spero Therapeutics is a clinical-stage biopharmaceutical company focused on advancing next-generation medicines for patients with serious immune-mediated diseases. The company’s lead program, SP001, is a third-generation, Fc-silent anti-CD40L monoclonal antibody being advanced first in IgG4-related disease, with potential for development in additional immunological & inflammatory diseases. For more information, visit www.sperotx.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include, but are not limited to, statements relating to Spero’s plans to advance SP001 into a Phase 2 study in IgG4-related disease; Spero’s plans to explore the use of SP001, and the role of CD40L inhibition, in additional autoimmune and inflammatory diseases; the anticipated benefits of the non-dilutive royalty-backed transaction, including the anticipated use of proceeds; Spero’s expectation that Utebzi will be made available to U.S. patients by the end of 2026; anticipated cash runway, and future milestones. Forward-looking statements are based on Spero’s current expectations and assumptions and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include, among others, risks related to the completion and integration of the Innovent transaction; Spero’s ability to successfully develop SP001; the timing and outcome of clinical trials and regulatory interactions; the ability to obtain and maintain regulatory approvals; potential safety, efficacy, manufacturing, supply, intellectual property, financing, competitive, and market risks; and other risks described in Spero’s filings with the Securities and Exchange Commission. Spero undertakes no obligation to update any forward-looking statements, except as required by law. Investor Relations Contact:Shai Biran, PhDSpero [email protected] Media Inquiries:[email protected]

New Drug Application (NDA) for tebipenem HBr for complicated urinary tract infections (cUTI), including pyelonephritis, is under review at the FDA, with PDUFA date of June 18, 2026 Spero maintains its cash runway guidance into 2028 CAMBRIDGE, Mass., May 13, 2026 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc. (Nasdaq: SPRO), a clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and diseases with high unmet need, today announced financial results for the first quarter ended March 31, 2026, and provided a business update. “We continue to make solid progress on the tebipenem HBr program alongside our licensing partner, GSK, as we prepare for the FDA’s decision expected in June,” said Esther Rajavelu, President and CEO of Spero Therapeutics. “With GSK's leadership in anti-infectives, tebipenem HBr, if approved, has the potential to meaningfully improve treatment options for cUTI patients. Looking ahead, we are positioning the company for the next phase by advancing other corporate activities, including exploring opportunities to grow our portfolio of clinical-stage product candidates.” Program Update Tebipenem HBr Tebipenem HBr is an investigational oral carbapenem antibiotic being developed for the treatment of cUTI, including pyelonephritis, to provide an effective oral therapeutic alternative to IV carbapenems. Spero granted GSK an exclusive license to commercialize tebipenem HBr in all territories, except certain Asian territories where Meiji holds development and commercialization rights. In February 2026, GSK announced that the U.S. Food and Drug Association (FDA) set the Prescription Drug User Fee Act (PDUFA) date to complete the review of the tebipenem HBr NDA as June 18, 2026. The NDA was submitted by GSK in December 2025, supported by results from the Phase 3 PIVOT-PO trial. The trial was stopped early for efficacy in May 2025, demonstrating non-inferiority of tebipenem HBr compared to intravenous imipenem-cilastatin in hospitalized patients with cUTI, including pyelonephritis, based on the overall response (composite of clinical cure plus microbiological eradication of the bacteria causing the infection) at the test of cure visit. The safety and tolerability profile of tebipenem HBr in PIVOT-PO was consistent with results reported in other studies with tebipenem and in line with that of the carbapenem antibiotic class. The most frequently reported adverse events were diarrhea and headache; these events were all mild or moderate and non-serious. For more information on the PIVOT-PO trial, please refer to ClinicalTrials.gov ID NCT06059846. First Quarter 2026 Financial Results Spero reported a net loss of $7.2 million for the first quarter of 2026 compared to a net loss of $13.9 million for the first quarter of 2025, or a diluted net loss per share of common stock of $0.13 and $0.25, respectively. Total revenue for the first quarter of 2026 was $0.3 million, compared to total revenue of $5.9 million for the first quarter of 2025. Research and development expenses for the first quarter of 2026 were $2.9 million, compared to $13.6 million of research and development expenses for the same period in 2025. The decrease was a result of decreased clinical activities related to our pivotal Phase 3 clinical trial of tebipenem HBr, which was stopped early for efficacy during the first half of 2025, and a decrease in personnel-related costs. General and administrative expenses for the first quarter of 2026 were $4.9 million, compared to $6.8 million of general and administrative expenses for the same period in 2025. The decrease was a result of decreased legal and personnel-related costs. As of March 31, 2026, cash and cash equivalents were $56.1 million. Spero maintains its cash runway guidance into 2028. For further details on Spero’s financials, refer to Spero’s Quarterly Report on Form 10-Q, filed with the U.S. Securities and Exchange Commission (SEC) today. Government Agency Research Support The views expressed in this press release are those of the authors and may not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government. Tebipenem HBr Research Support Select tebipenem HBr studies have been funded in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; and Biomedical Advanced Research and Development Authority, under contract number HHSO100201800015C. About Spero Therapeutics Spero Therapeutics, headquartered in Cambridge, Massachusetts, is a clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and diseases with high unmet need. For more information, visit www.sperotherapeutics.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the potential for tebipenem HBr to meaningfully improve treatment options for cUTI patients, if approved; the anticipated PDUFA date set by the FDA as June 18, 2026; Spero’s exploration of opportunities to expand its portfolio of clinical stage product candidates; the potential of tebipenem HBr to be the first oral carbapenem antibiotic for US patients with cUTI, including pyelonephritis, and to set a new standard of care; the potential receipt of milestone payments under Spero’s license and collaboration agreements; Spero’s estimation that its cash and cash equivalents as of March 31, 2026 will be sufficient to fund operations into 2028; and the potential benefits of any of Spero’s current or future product candidates in treating patients. In some cases, forward-looking statements may be identified by terms such as “may,” “will,” “should,” “expect,” “plan,” “aim,” “anticipate,” “could,” “intent,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue,” the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of important risks, uncertainties and other factors that may cause actual results to differ materially from those indicated by such forward looking statements, including whether the FDA will ultimately approve tebipenem HBr and, if so, the timing of any such approval, taking into account the effects of possible regulatory delays; whether the FDA will require any additional clinical data or place labeling restrictions on the use of tebipenem HBr that would delay approval and/or reduce the commercial prospects of tebipenem HBr; whether a successful commercial launch can be achieved and market acceptance of tebipenem HBr can be established; Spero’s reliance on third parties to manufacture, develop, and commercialize its product candidates, if approved; Spero’s reliance on GSK, pursuant to the exclusive GSK License Agreement, to advance development of tebipenem HBr and GSK’s right thereunder to determine, in its sole discretion, whether to further develop and commercialize tebipenem HBr; Spero’s need for additional funding; Spero’s ability to retain key personnel; whether Spero’s cash resources will be sufficient to fund its continuing operations for the periods anticipated; and other factors discussed in the “Risk Factors” set forth in filings that Spero periodically makes with the SEC. The forward-looking statements included in this press release represent Spero’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Spero explicitly disclaims any obligation to update any forward-looking statements. Investor Relations Contact: Shai Biran, PhD Spero Therapeutics [email protected] Media Inquiries: [email protected] -- Tables –

Spero announced the resubmission of tebipenem HBr New Drug Application (NDA) to the FDA for complicated urinary tract infections (cUTI), including pyelonephritis in December 2025 In February, Spero’s licensing partner, GSK announced the FDA had set the PDUFA date as June 18, 2026 Spero estimates cash and cash equivalents as of December 31, 2025 are sufficient to fund current operations into 2028 CAMBRIDGE, Mass., March 26, 2026 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc. (Nasdaq: SPRO), a clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and diseases with high unmet need, today announced financial results for the fourth quarter and full year ended December 31, 2025, and provided a business update. “2025 was marked by important progress across the tebipenem HBr program in cUTI, including completion of the global Phase 3 trial and resubmission of the NDA,” said Esther Rajavelu, President and CEO of Spero. “With our licensing partner GSK’s global leadership in anti-infectives, tebipenem HBr, if approved, has the potential to address an important need and meaningfully improve treatment options for patients with cUTI. We look forward to the FDA’s decision in late June as we continue to execute our business strategy to deliver innovative therapies.” Spero remains focused on completing its obligations under its License Agreement with GSK while advancing other corporate activities, including exploring opportunities to expand its portfolio of clinical-stage product candidates. Program Update Tebipenem HBr Tebipenem HBr is an investigational oral carbapenem antibiotic being developed for the treatment of cUTI, including pyelonephritis, to provide an effective oral therapeutic alternative to IV carbapenems. Spero granted GSK an exclusive license to commercialize tebipenem HBr in all territories, except certain Asian territories where Meiji holds development and commercialization rights. In December 2025, GSK resubmitted the tebipenem HBr NDA to the FDA. In February 2026, GSK announced that the FDA set the Prescription Drug User Fee Act (“PDUFA”) date as June 18, 2026. The NDA is supported by results from the successful Phase 3 PIVOT-PO trial that evaluated tebipenem HBr. The trial, which was stopped early for efficacy in May 2025, demonstrated non-inferiority of tebipenem HBr compared to intravenous imipenem-cilastatin in hospitalized patients with cUTI, including pyelonephritis, based on the overall response (composite of clinical cure plus microbiological eradication of the bacteria causing the infection) at the test of cure visit. Detailed results were presented in a late-breaking oral abstract session at IDWeek 2025. The safety and tolerability profile of tebipenem HBr in PIVOT-PO was consistent with results reported in other studies with tebipenem and in line with that of the carbapenem antibiotic class. The most frequently reported adverse events were diarrhea and headache; these events were all mild or moderate and non-serious. For more information on the PIVOT-PO trial, please refer to ClinicalTrials.gov ID NCT06059846. Fourth Quarter and Full Year 2025 Financial Results Spero reported net income of $31.5 million for the fourth quarter of 2025 compared to a net loss of $(20.9) million for the fourth quarter of 2024, or a diluted net gain and net income per share of common stock of $0.53 and a diluted net loss and net loss per share of common stock of $(0.38), respectively. Net income for the year ended December 31, 2025, was $8.6 million compared to a net loss for the year ended December 31, 2024, of $(68.6) million, or a diluted net gain per share of common stock of $0.15 and a diluted net loss per share of common stock of $(1.27), respectively. Total revenue for the fourth quarter of 2025 was $41.3 million, compared to total revenue of $15.0 million for the fourth quarter of 2024. The revenue increase for the fourth quarter of 2025 was primarily due to an increase in collaboration revenue from our agreements with GSK and Pfizer. Total revenue for the year ended December 31, 2025, was $66.8 million, compared to $48.0 million for the year ended December 31, 2024. The revenue increase for the year was primarily due to the aforementioned collaboration revenue related to our agreements with GSK and Pfizer. Research and development expenses for the fourth quarter of 2025 were $5.6 million, compared to $28.8 million of research and development expenses for the same period in 2024. Research and development expenses for the year ended December 31, 2025, were $38.5 million, compared to $96.8 million for the year ended December 31, 2024. The decrease in research and development expenses year-over-year was primarily due to decreased clinical trial activity related to the PIVOT-PO trial. General and administrative expenses for the fourth quarter of 2025 were $4.3 million, compared to $7.1 million of general and administrative expenses for the same period in 2024. This decrease was primarily due to decreased legal and personnel related costs. General and administrative expenses for the year ended December 31, 2025, were $21.2 million, compared to $23.7 million for the year ended December 31, 2024, with lower expenses in 2025 compared to 2024 primarily due to decreases in legal, consulting and personnel related costs. As of December 31, 2025, Spero had cash and cash equivalents of $40.3 million. Spero estimates that its cash and cash equivalents as of December 31, 2025 will be sufficient to fund current operations into 2028. In Q1 2026, Spero received a $25 milestone payment from GSK, triggered by the tebipenem HBr NDA resubmission. For further details on Spero’s financials, refer to Spero’s Annual Report on Form 10-K, filed with the U.S. Securities and Exchange Commission (SEC) today. Government Agency Research Support The views expressed in this press release are those of the authors and may not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government. Tebipenem HBr Research Support Select tebipenem HBr studies have been funded in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; and Biomedical Advanced Research and Development Authority, under contract number HHSO100201800015C. About Spero Therapeutics Spero Therapeutics, headquartered in Cambridge, Massachusetts, is a clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and diseases with high unmet need. For more information, visit www.sperotherapeutics.com. Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the anticipated PDUFA date set by the FDA as June 18, 2026;; Spero’s exploration of opportunities to expand its portfolio of clinical stage product candidates; the potential of tebipenem HBr to be the first oral carbapenem antibiotic for US patients with cUTI, including pyelonephritis, and to set a new standard of care; the potential receipt of milestone payments under Spero’s license and collaboration agreements; Spero’s estimation that its cash and cash equivalents as of December 31, 2025 will be sufficient to fund operations into 2028; and the potential benefits of any of Spero’s current or future product candidates in treating patients. In some cases, forward-looking statements may be identified by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intent," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue," the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of important risks, uncertainties and other factors that may cause actual results to differ materially from those indicated by such forward looking statements, including whether the FDA will ultimately approve tebipenem HBr and, if so, the timing of any such approval, taking into account the effects of possible regulatory delays; whether the FDA will require any additional clinical data or place labeling restrictions on the use of tebipenem HBr that would delay approval and/or reduce the commercial prospects of tebipenem HBr; whether a successful commercial launch can be achieved and market acceptance of tebipenem HBr can be established; Spero's reliance on third parties to manufacture, develop, and commercialize its product candidates, if approved; Spero’s reliance on GSK pursuant to the exclusive GSK License Agreement advance development of tebipenem HBr and GSK’s right thereunder to determine, in its sole discretion, whether to further develop and commercialize tebipenem HBr; Spero's need for additional funding; Spero's ability to retain key personnel; whether Spero's cash resources will be sufficient to fund its continuing operations for the periods anticipated; and other factors discussed in the "Risk Factors" set forth in filings that Spero periodically makes with the SEC. The forward-looking statements included in this press release represent Spero's views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Spero explicitly disclaims any obligation to update any forward-looking statements. Investor Relations Contact: Shai Biran, PhD Spero Therapeutics [email protected] Media Inquiries: [email protected]

Results from PIVOT-PO Phase 3 trial evaluating tebipenem HBr in complicated urinary tract infection (cUTI) presented as IDWeek late-breaker in October 2025 Spero’s development partner, GSK, plans to submit data from the PIVOT-PO trial as part of a planned US Food and Drug Administration (FDA) filing in 4Q 2025 Company expects current cash and cash equivalents to fund operations into 2028 CAMBRIDGE, Mass., Nov. 13, 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 financial results for the third quarter ended September 30, 2025, and provided a business update. “We are pleased to have shared the Phase 3 PIVOT-PO study results for tebipenem HBr with the medical community at this year’s IDWeek conference in October,” said Esther Rajavelu, Chief Executive Officer of Spero. “We are working alongside our partner, GSK, to enable them to submit the FDA filing this quarter and we anticipate regulatory decision in 2H 2026. If approved, tebipenem HBr as an oral option could provide an important alternative to IV carbapenem therapies for complicated urinary tract infections, with the potential to shorten hospital stays and improve treatment burden for patients.” Pipeline Update Tebipenem HBr Tebipenem HBr is an investigational oral carbapenem antibiotic being developed for the treatment of cUTI, including pyelonephritis, to provide an effective oral therapeutic taken outside a hospital setting. Spero granted GSK an exclusive license to commercialize tebipenem HBr in all territories, except certain Asian territories where Meiji holds development and commercialization rights. In October 2025, results from the Phase 3 PIVOT-PO trial evaluating tebipenem HBr, were presented in a late-breaking oral abstract session at IDWeek 2025. The trial, which was stopped early for efficacy in May 2025, demonstrated non-inferiority of tebipenem HBr compared to intravenous imipenem-cilastatin in hospitalized patients with cUTI, including pyelonephritis, based on the overall response (composite of clinical cure plus microbiological eradication of the bacteria causing the infection) at the test of cure visit. Tebipenem HBr (oral, 600 mg) achieved a 58.5% overall success rate (261/446 participants) compared to 60.2% overall success rate (291/483 participants) for imipenem-cilastatin (intravenous, 500 mg) (adjusted treatment difference: 1.3%; 95% CI: 7.5%, 4.8%). The safety and tolerability profile of tebipenem HBr in PIVOT-PO was consistent with results reported in other studies with tebipenem and in line with that of the carbapenem antibiotic class. The most frequently reported adverse events (in 3% of patients who received tebipenem HBr) were diarrhea and headache; these events were all mild or moderate and non-serious. The PIVOT-PO results will form part of GSK’s planned FDA submission in Q4 2025. For more information on the PIVOT-PO trial, please refer to ClinicalTrials.gov ID NCT06059846. SPR720 SPR720 is an investigational prodrug that was studied as an antibiotic for nontuberculous mycobacterium pulmonary disease (NTM-PD). The Company has discontinued the SPR720 program in Q3 2025, following a review of the complete data from Phase 2a and Phase 1 trials in patients with NTM-PD. Third Quarter 2025 Financial Results Spero reported a net loss of $7.4 million for the third quarter of 2025 compared to a net loss of $17.1 million for the third quarter of 2024, or a diluted net loss per share of common stock of $0.13 and $0.32, respectively. Total revenue for the third quarter of 2025 was $5.4 million, compared with total revenue of $13.5 million for the third quarter of 2024. The revenue decrease for the third quarter of 2025 was primarily due to decreased collaboration revenue with GSK, as well as a decrease in grant revenue. Research and development expenses for the third quarter of 2025 were $8.6 million, compared to $26.9 million of research and development expenses for the same period in 2024. The decrease in research and development expenses compared with the prior year period was primarily due to reduced clinical expenses related to the PIVOT-PO Trial and lower expenses on the SPR720 clinical program. General and administrative expenses for the third quarter of 2025 were $4.2 million, compared to $5.2 million of general and administrative expenses for the same period in 2024. This decrease compared with the prior year-period was primarily due to a decrease in personnel-related costs. As of September 30, 2025, Spero had cash and cash equivalents of $48.6 million. Spero estimates that its existing cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditures into 2028. For further details on Spero’s financials, refer to Spero’s Quarterly Report on Form 10-Q, filed with the U.S. Securities and Exchange Commission (SEC) today. Government Agency Research Support The views expressed in this press release are those of the authors and may not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government. Tebipenem HBr Research Support Select tebipenem HBr studies have been funded in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; and Biomedical Advanced Research and Development Authority, under contract number HHSO100201800015C. About Spero Therapeutics Spero Therapeutics, headquartered in Cambridge, Massachusetts, is a clinical-stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and MDR bacterial infections with high unmet need. For more information, visit www.sperotherapeutics.com. Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the timing and results of Spero's Phase 3 PIVOT-PO trial; the timing of a planned FDA filing in 4Q 2025 for tebipenem HBr and the timing of a regulatory decision for tebipenem HBr in 2H 2026; the potential of tebipenem HBr to be the first oral carbapenem antibiotic for US patients with cUTI, including pyelonephritis, and to set a new standard of care; the potential receipt of milestone payments under Spero’s license and collaboration agreements; Spero’s anticipated cash runway; and the potential benefits of any of Spero’s current or future product candidates in treating patients. In some cases, forward-looking statements may be identified by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intent," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue," the negative of these terms or other similar expressions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of important risks, uncertainties and other factors that may cause actual results to differ materially from those indicated by such forward looking statements, including whether the results of any of Spero’s clinical trials will warrant submission for approval from the FDA or equivalent foreign regulatory agencies; whether the FDA will ultimately approve tebipenem HBr and, if so, the timing of any such approval, taking into account the effects of possible regulatory delays; whether the FDA will require any additional clinical data or place labeling restrictions on the use of tebipenem HBr that would delay approval and/or reduce the commercial prospects of tebipenem HBr; whether a successful commercial launch can be achieved and market acceptance of tebipenem HBr can be established; Spero's reliance on third parties to manufacture, develop, and commercialize its product candidates, if approved; Spero’s reliance on GSK pursuant to the exclusive GSK License Agreement to develop tebipenem HBr and GSK’s right thereunder to determine, in its sole discretion, whether to further develop tebipenem HBr; Spero's need for additional funding; Spero's ability to retain key personnel; whether Spero's cash resources will be sufficient to fund its continuing operations for the periods anticipated; and other factors discussed in the "Risk Factors" set forth in filings that Spero periodically makes with the SEC. The forward-looking statements included in this press release represent Spero's views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Spero explicitly disclaims any obligation to update any forward-looking statements. Investor Relations Contact: Shai Biran, PhD Spero Therapeutics [email protected] Media Inquiries: [email protected]