Spero Therapeutics Shares SPR720 Phase 2a Interim Results and Business Update

Spero Therapeutics, Inc., a clinical-stage biopharmaceutical company based in Cambridge, Massachusetts, has announced that its Phase 2a proof-of-concept study of SPR720 for the treatment of Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD) did not achieve its primary endpoint. This conclusion was based on an interim analysis involving 16 patients. While the data demonstrated antimicrobial activity connected with SPR720, the analysis did not show a significant difference from the placebo. Furthermore, potential dose-limiting safety concerns were noted, including three instances of reversible grade 3 hepatotoxicity in patients administered 1,000 mg orally once daily.

Given these results, Spero has decided to halt the current development of SPR720, opting to analyze the remaining data before determining future steps. This decision will also lead to a restructuring and a workforce reduction by approximately 39%, which is expected to extend the company's cash runway into mid-2026. The restructured operations will enable Spero to focus on the development of its other key programs, including tebipenem HBr and SPR206, and pursue potential strategic initiatives.

Sath Shukla, Spero’s President and CEO, expressed gratitude to the team and trial participants for their efforts, despite the disappointing outcome. He reiterated Spero's commitment to developing new treatments for patients with critical needs, highlighting the continued advancements in the tebipenem HBr and SPR206 programs.

Spero's financial status at the end of Q3 2024 showed an unaudited cash balance of $76.3 million. The company believes that, with the restructuring and anticipated funding, it has adequate resources to support its operations into mid-2026. This includes the ongoing global Phase 3 PIVOT-PO clinical trial for tebipenem HBr and preparation for a Phase 2 trial for SPR206, contingent on securing additional non-dilutive funding.

SPR720 is an oral prodrug that converts rapidly in the body to SPR719, targeting DNA gyrase B in mycobacteria, a mechanism distinct from other antibiotics used for NTM-PD. The Phase 2a trial, completed in July 2024, enrolled 25 patients but failed to meet its primary endpoint, demonstrating no significant difference from placebo in reducing bacterial colony counts.

Tebipenem HBr, an oral carbapenem antibiotic, is being developed for complicated urinary tract infections (cUTI) to potentially reduce hospital stays. Spero has licensed the rights to commercialize tebipenem HBr to GSK, excluding certain Asian territories. The licensing agreement, signed in 2022, included an upfront payment of $66 million, with additional milestone payments totaling $30 million by Q3 2023. The company stands to receive further milestone payments upon patient enrollment in the PIVOT-PO trial and subsequent commercial achievements, potentially reaching up to $400 million, alongside royalties on net sales.

The PIVOT-PO Phase 3 trial is set to enroll approximately 2,648 patients, comparing oral tebipenem HBr with intravenous imipenem-cilastatin in hospitalized adults with cUTI or acute pyelonephritis. The trial aims to complete enrollment by the second half of 2025, with the primary endpoint being an overall response at the Test-of-Cure visit.

SPR206 is another promising candidate, an intravenously administered next-generation polymyxin, effective against multi-drug resistant Gram-negative bacteria. The FDA has approved Spero's Investigational New Drug (IND) application for a Phase 2 trial in patients with hospital-acquired or ventilator-associated bacterial pneumonia, pending additional funding.

Spero Therapeutics continues its mission to develop innovative treatments for rare diseases and multi-drug resistant bacterial infections, with a focus on addressing significant unmet medical needs.