Spero Therapeutics, Inc.

Good afternoon and welcome to the Spear Therapeutics fourth quarter and full year 2024 earnings conference call. At this time, all participants are in listen-only mode. Following the company's formal remarks, 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 information on the replay and for further information related to today's announcement on the Spear Therapeutics website at www.speartherapeutics.com. At this time, I would like to turn the call over to Shai Biren, Senior Director, Investor Relations. Mr. Biren, 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 fourth quarter and full year 2024. 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 securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our actual clinical programs, future results, progress, timing, performances, or achievements to differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties associated with our business and factors that could cause or contribute to such differences are described in detail in Sparrow Therapeutics' filings with the SEC, including in the risk factors section of its earnings report on Form 10-K for the year ended December 31, 2024, filed with the SEC today. Joining me on the call today are Esther Ajavelu, our Interim Chief Executive Officer and Chief Financial Officer, and Tim Koitzer, Sparrow's Chief Operating Officer. There will be a Q&A session following the prepared remarks. I will now turn the call over to Esther to begin.

Thank you, Shai. Good afternoon, everyone, and thank you for joining our full year 2024 earnings and business update call. Sparotherapeutics is a clinical stage biopharmaceutical company focused on identifying and developing novel treatments for rare diseases and multidrug-resistant bacterial infections with high unmet medical need. Our most advanced clinical stage product candidate, tebupenem HVR, is in a phase three trial with the potential to be the first broad-spectrum oral carbapenem to treat adult patients with complicated urinary tract infections, including acute pyelonephritis. These are patients who have limited or no alternative treatment options and would otherwise likely be treated with an IV carbapenem. Sparrow is co-developing tebupenem HBR with our partner GSK. Today, we announced that a pre-specified interim analysis in the Phase III PIVOT-PO clinical trial is expected to be completed in the second quarter of 2025. Our top priority for this year is the continued advancement of the tebupenem program, which, if approved, has the potential to fundamentally change the treatment paradigm for complicated UTI by offering patients and prescribers a convenient oral treatment option. Next, on to SPR720, our novel gyrase B inhibitor that was in a phase 2A proof-of-concept study as an oral treatment for non-tuberculous mycobacterial pulmonary disease, or NTMPD. The trial was randomized, double-blind, placebo-controlled, and enrolled 25 treatment-naive or treatment-experienced patients with non-refractory NTM pulmonary disease. caused by mycobacterium avium complex or MAC infections. The primary endpoint of the study was change in bacterial load in sputum samples from baseline to the end of the 56-day treatment period. Key secondary endpoints included assessments of safety and tolerability, clinical response, PK, and certain other measures. Enrollment concluded in July 2024. In October 2024, we completed a planned interim analysis, which included 16 patients who had completed dosing and post-dose follow-up visits. Results from the interim analysis 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, dosed at 1,000 milligrams once daily. We are completing assessment of the full data set of all 25 patients dosed in the trial and plan to determine next steps for the program once that is complete. Lastly, on our pipeline, following a thorough review and reprioritization, we made the decision to discontinue development of SPR-206, an IV-administered next-gen polymyxin antibiotic that cleared an IND in 2024 for a Phase II trial in hospital-acquired and ventilator-associated bacterial pneumonia. To date, we have made good progress on the Phase III trial for our lead asset, tebupenem HBR, and we look forward to completing the pre-specified interim analysis next quarter, and with our partner, GSK, share an update on next steps for the program. As a reminder, following completion of the Tebby Penham HBR Phase III trial, GSK is expected to assume responsibility for regulatory and commercialization efforts. And if these are successfully pursued, Sparrow could qualify for about $400 million in contingent milestones, including $25 million when GSK submits an NDA and subsequent milestones based on commercialization and sales ramp. With that, I'll turn the call over to Tim.