Q2 2025 Spero Therapeutics Inc Earnings Call & Business Update

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: Esther will provide an update on our lead clinical program, Pevipenem 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 Pevipenem HBR could fill, followed by a brief update on SBR 720.

Speaker #1: 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.

Speaker #2: 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 3 PivotPO trial evaluating Pevipenem HBR in patients with COTI, including pyelonephritis, successfully met its primary endpoint and was stopped early for efficacy.

Speaker #2: This decision follows a recommendation from the Independent Data Monitoring Committee (IDMC), which reviewed data from a pre-specified interim analysis based on 1,690 patients enrolled in the trial.

Speaker #2: The primary endpoint was overall response at the test of cure visit, a composite of clinical cure plus microbiological eradication. Pevipenem HBR demonstrated non-inferiority to intravenous imipenem silistatin in hospitalized adult patients with COTI, including pyelonephritis.

Speaker #2: The positive outcome from the PivotPO trial further supports our thesis that Pevipenem HBR and oral carbapenem can deliver comparable treatment outcomes to standard of care IV carbapenem therapy.

Speaker #2: The IDMC review did not identify any new safety concerns beyond what had been reported in prior Pevipenem studies. Diarrhea and headache were the two most reported adverse events.

Speaker #2: We in GSK plan to submit the full results from PivotPO for presentation at an upcoming scientific conference and for publication in a peer-reviewed journal.

Speaker #2: GSK's responsible for regulatory filings and has communicated that they plan to work with the FDA to include the PivotPO data as part of an FDA filing at 2025.

Speaker #2: We currently believe that FDA action is likely in the second half of 2026. Spero will support GSK in the preparation of the filing and any potential pre-approval communications with the FDA.

Speaker #2: 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 Pevipenem HBR as a treatment for COTIs including pyelonephritis for a limited use indication.

Speaker #2: As a reminder, our agreement with GSK grants them an exclusive license to develop and commercialize Pevipenem HBR in all territories except for Japan and certain other Asian countries that are covered by our partnership with Meiji Seika Pharmaco.

Speaker #2: While Spero's responsible for the execution and cost of the PivotPO 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.

Speaker #2: Assuming these activities are successfully pursued, Spero could qualify for up to $350 million in contingent milestones. Including $25 million when GSK submits the US regulatory filing, and subsequent milestones based on commercialization and sales ramp, as well as tiered royalties on net sales.

Speaker #2: Our press release and 10-Q filed this evening includes 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.

Speaker #2: I will now turn the call over to Tim, who will provide additional details on the TEPI program and SBR 720.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: They are also more likely to involve multi-drug resistant or MDR pathogens. If not properly treated, complicated UTIs can recur repeatedly or escalate into more severe conditions, including sepsis and septic shock.

Speaker #1: They are a leading cause of hospitalization and contribute to over $6 billion per year in U.S. healthcare costs, or prolonged outpatient IV therapy, adding significant complexity and cost to their treatment.

Speaker #1: The lack of an effective, well-tolerated oral alternative has left a major gap in care. If approved, we believe Pevipenem Hydrobromide is well positioned to change the treatment landscape for patients with COTIs.

Speaker #1: 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.

Speaker #1: Next, on to SBR 720, our novel diurease B inhibitor that was in a Phase 2A proof-of-concept study as an oral treatment for patients with non-tuberculosis mycobacterial pulmonary disease, or NTMPD.

Speaker #1: 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.

Speaker #1: 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 III hepatotoxicity in the high-dose cohort receiving 1,000 milligrams once daily.

Speaker #1: The assessment of the full dataset of all 25 patients dosed in the trial is now complete, and we are currently determining the next steps for the program.

Speaker #1: I will now hand the call back to Esther for a review of our financials. Thank you for your attention.

Speaker #2: Thank you, Tim. As of June 30, Spero had cash-in-cash equivalents of $31.2 million. We estimate that our existing cash-in-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.

Speaker #2: As I mentioned during the first part of the call, we achieved meaningful cost savings as the PivotPO trial met the primary endpoint following the pre-specified interim analysis with fewer enrolled patients than originally planned.

Speaker #2: These trial cost offsets 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.

Speaker #2: 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.

Speaker #2: The decrease in R&D expenses year over year was primarily due to reduced clinical expense related to the PivotPO 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.

Speaker #2: 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 2025, compared with a net loss of $17.9 million for the second quarter of 2024.

Speaker #2: 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 10-Q filed with the SEC this evening.

Speaker #2: Before opening the call for questions, I want to reiterate how excited we are about the positive PivotPO result. We believe that Pevipenem HBR is now one step closer to being the first commercial product to emerge from Spero's pipeline, with the potential to meaningfully improve the standard of care for patients with COTI.

Speaker #2: 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 fulfilling unmet medical needs within the anti-infective therapeutic area, and my colleagues here at Spero for their hard work and dedication to improving patient outcomes.

Speaker #2: With that, we will now open the call for questions. Operator?

Speaker #1: Thank you. We will now begin the question and answer session. To ask a question, you may press Start, then 1 on your touchstone phone.

Speaker #1: 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 Start, then 2.

Speaker #1: At this time, we will pause momentarily to assemble our roster. The first question comes from Gavin Clark with Evercrow. Please go ahead.

Speaker #3: Yeah, hi, this is Gautam on for Gavin. Thanks for taking our question. So, we have one question on capital allocation. How are we paying in terms of, you know, allocating capital? Would you be focusing on BD, or would it go to more pipeline?

Speaker #3: Any guidance there would be helpful.

Speaker #2: Sure. Thanks for the question. So, you know, our primary objective is to make sure that PEPI gets through the regulatory process and gets to approval because that would be the real value driver.

Speaker #2: 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.

Speaker #3: Got it, thank you.

Speaker #1: Thank you. To ask a question, you may press Start and 1. Again, if you have a question, please press Start, then 1. Thank you.

Speaker #1: This concludes our question and answer session. I would like to turn back the conference over to the management for closing remarks.

Speaker #4: Thank you, everyone, for joining the call. We will talk to you soon.