Spero Therapeutics, Inc.

Good afternoon and welcome to Sparrow Therapeutics second quarter 2025 earnings conference call. At this time, all participants are in the listen-only mode. Following the company's formal remark, we will open up the call for questions. Please be advised that this call is being recorded and a replay will be available. You can find the information in the replay and further information related to today's announcement on the Sparrow Therapeutics website at www.sperrotherapeutics.com. At this time, I would like to turn the call over to Shahi Biran, Senior Director, Investor Relations. Mr. Biran, please go ahead.

Thank you, Operator, and thank you all for participating in today's conference call. This afternoon, Sparrow Therapeutics released financial results and provided a business update for the second quarter of 2025. The press release is available on the investor page of the Sparrow 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 under the Private Securities Litigation Reform Act of 1995 as amended. These forward-looking statements are based on management's current expectations and beliefs and are subject to risks, uncertainties, and other factors that may cause actual results to differ materially from those indicated by such forward-looking statements. These risks uncertainties, and other factors are described in detail in Sphero-Therapeutics filings with the SEC, including in the risk factors set forth in the periodic report on Form 10-Q for the second quarter ended June 30, 2025, filed with the SEC today. Leading our call today will be Esther Rajavelu, our Chief Executive Officer and Chief Financial Officer. She will be joined by our Chief Operating Officer, Tim Koitzer. Esther will provide an update on our lead clinical program, Tevipenem HBR, for complicated urinary tract infections, or COTIs. Then, Tim will provide an overview of the COTI therapeutic landscape and the unmet need we believe Tevipenem HBR could fill, followed by a brief update on SPR 720. Esther will then conclude with a review of our financials before opening the call for questions. I will now turn the call over to Esther.

Thank you, Shai. Good afternoon, everyone, and thank you for joining our second quarter 2025 earnings and business update call. I'm very pleased to share that in May of this year, together with our development partner, GSK, We announced that the Phase III PIVOT-PO trial evaluating tebupenem HVR in patients with CUTI, including pyelonephritis, successfully met its primary endpoint and was stopped early for efficacy. This decision follows a recommendation from the Independent Data Monitoring Committee, or IDMC, which reviewed data from a pre-specified interim analysis based on 1,690 patients enrolled in the trial. The primary endpoint was overall response at the test of cure visit, a composite of clinical cure plus microbiological eradication. Tebupenem HBR demonstrated non-inferiority to intravenous imipenem psilostatin in hospitalized adult patients with CUTI, including pyelonephritis. The positive outcome from the PIVOT-PO trial further supports our thesis that tebupenem HBR and oral carbapenem can deliver comparable treatment outcomes to standard-of-care IV carbapenem therapy. The ID&C review did not identify any new safety concerns beyond what had been reported in prior carbapenem studies. Diarrhea and headache were the two most reported adverse events. We and GSK plan to submit the full results from Pivot-PO for presentation at an upcoming scientific conference and for publication in a peer-reviewed journal. GSK is responsible for regulatory filings and has communicated that they plan to work with the FDA to include the PIVOT PO data as part of an FDA filing at ERN 2025. We currently believe that FDA action is likely in the second half of 2026. Sparrow will support GSK in the preparation of the filing and any potential pre-approval communications with the FDA. The PivotPO study is covered by the Special Protocol Assessment Agreement entered into with the FDA in 2023. The FDA has indicated that positive and persuasive results from the PivotPO, together with results from previously completed studies, could be sufficient to support approval of tebupenem-HBR as a treatment for CUTIs, including pyelonephritis, for a limited use indication. As a reminder, our agreement with GSK grants them an exclusive license to develop and commercialize tebupenem-HBR in all territories except for Japan and certain other Asian countries that are covered by our partnership with Meiji Seika Pharmaco. While Sparrow is responsible for the execution and cost of the PIVOT-PO trial, GSK is responsible for the execution and cost of the planned regulatory filings and commercialization activities, as well as any future clinical development activities. Assuming these activities are successfully pursued, Sparrow could qualify for up to 351 million in contingent milestones, including 25 million when GSK submits the U.S. regulatory filing. and subsequent milestones based on commercialization and sales ramp, as well as tiered royalties on net sales. Our press release and 10-Q filed this evening include additional details on these contingent payments. Importantly, with the trial stopping early for efficacy, we have achieved meaningful cost savings in the near term, which we anticipate will extend our cash runway into 2028 based on our current operating plan. I will now turn the call over to Tim, who will provide additional details on the TEBI program and FPR 720.

Thank you, Esther, and hello, everyone. We estimate that there are approximately 2.9 million episodes of complicated urinary tract infections each year in the United States alone. These infections typically occur in patients with structural or functional abnormalities of the urinary tract, in patients requiring catheters, or in patients with comorbidities such as kidney infections. They are also more likely to involve multidrug-resistant, or MDR, pathogens. If not properly treated, complicated UTIs can recur repeatedly or escalate into more severe conditions, including sepsis and septic shock. They are a leading cause of hospitalization and contribute to over $6 billion per year in U.S. healthcare costs. Currently, the standard of care for many infections caused by MDR gram-negative bacteria including CUTIs, is carbapenem antibiotics. However, carbapenems are currently only available in IV form. This means patients often require inpatient admission or prolonged outpatient IV therapy, adding significant complexity and cost to their treatment. The lack of an effective, well-tolerated oral alternative has left a major gap in care. If approved, we believe tebupenem and hydrobromide is well-positioned to change the treatment landscape for patients with CUTIs. offering an oral option where currently IV therapy is the standard of care. We believe the product would represent a major clinical advance for patients and has the potential to create significant economic benefits for the healthcare system. Next, on to SPR-720, our novel gyrase B inhibitor that was in a Phase IIa proof-of-concept study as an oral treatment for patients with non-tuberculous mycobacterial pulmonary disease, or NTMPD. In October of 2024, we completed a planned interim analysis of the trial, results from which showed that the study did not meet its primary endpoint. While there was some evidence of antimicrobial activity, the treated arm did not show sufficient separation from placebo. In addition, we saw potential dose-limiting safety signals, including three cases of reversible grade 3 hepatotoxicity in the high-dose cohort receiving 1,000 milligrams once daily. The assessment of the full data set of all 25 patients dosed in the trial is now complete, and we are currently determining the next steps for the program. I will now hand the call back to Esther for a review of our financials. Thank you for your attention.

Thank you, Tim. As of June 30th, Sparrow had cash and cash equivalents of $31.2 million. We estimate that our existing cash and cash equivalents Together with the remaining $23.8 million in earned and non-contingent development milestone payments received from GSK in August 2025 will be sufficient to fund the company's current operating and capital expenditures into 2028. As I mentioned during the first part of the call, we achieved meaningful cost savings as the Pivot PO trial met the primary endpoint following the pre-specified interim analysis with fewer enrolled patients than originally planned. These trial cost aspects are the primary driver of our extended runway. Total revenue for the second quarter of 2025 was $14.2 million compared with total revenue of $10.2 million for the second quarter of 2024. The revenue increase compared with the prior year period was primarily due to collaboration revenue from GSK. R&D expenses for the second quarter of 25 were 10.7 million compared to 23.7 million for the same period in 2024. The decrease in R&D expenses year over year was primarily due to reduced clinical expense related to the PIVOT-PO study. G&E expenses for the second quarter of 25 were 5.9 million compared to 5.5 million for the same period in 24. This increase compared with the prior year period was primarily due to increased personnel and professional services expenses. The company reported a net loss of $1.7 million for the second quarter of 25 compared with a net loss of $17.9 million for the second quarter of 24. Diluted net loss per share of common stock was $0.03 and $0.33 for these periods respectively. For further details on our financials, please refer to our 10Q filed with the SEC this evening. Before opening the call for questions, I want to reiterate how excited we are about the positive PIVOT-PO results. We believe that Tebipenem HBR is now one step closer to being the first commercial product to emerge from Sparrow's pipeline, with the potential to meaningfully improve the standard of care for patients with CUTI. I want to take this opportunity to thank the patients and investigators who participated in our clinical program, our partner, GSK, for their ongoing commitment to fulfill unmet medical needs within the anti-infective therapeutic area, and my colleagues here at Sparrow for their hard work and dedication to improve patient outcomes.

With that, we will now open the call for questions. Operator?

Thank you. We will now begin the question and answer session. To ask a question, you may press star then 1 on your touch tone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then 2. At this time, we will pause momentarily to assemble our oyster.

The first question comes from Gavin Clark with Evercore.

Please go ahead.

Yeah, hi, this is Gautam on for Gavin. Thanks for taking our question. So we have one question on the capital allocation. How are you working in terms of, you know, capital would be, would you be focusing on BD or would go to more pipeline? Any guidance there would be helpful.

Thanks for the question.

Our primary objective is to make sure that PEBI gets through the regulatory process and gets to approval because that would be the real value driver going forward. Our runway currently considers funding, making sure that we're well-funded to get that to the finish line. Following that, we would make decisions on what happens with the capital once we have line of sight into approval.

Got it. Thank you. Thank you.

To ask a question, you may press star N1.

Again, if you have a question, please press star then 1. Thank you.

This concludes our question and answer session. I would like to turn back the conference over to the management for closing remarks.

Thank you everyone for joining the call. We will talk to you soon.

Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect. Thank you.