Spero Therapeutics Publishes SPR720 Phase 1 Lung Data in AAC

Spero Therapeutics, Inc., a clinical-stage biopharmaceutical company based in Cambridge, Massachusetts, has announced promising results from its Phase 1 clinical trial of SPR719, the active moiety of SPR720. The study, aimed at evaluating the intrapulmonary pharmacokinetics (PK) of SPR719, has been published in the journal Antimicrobial Agents and Chemotherapy. SPR720, an orally administered, chemically stable phosphate ester prodrug, is rapidly converted to SPR719 in the body. This active compound targets the ATPase site of DNA gyrase B in mycobacteria, a unique mechanism compared to other antibiotics used for Non-Tuberculous Mycobacterial Pulmonary Disease (NTM-PD).

NTM-PD is caused by bacteria found in natural environments like soil, dust, and water. These bacteria belong to the Mycobacterium family, but do not include the ones causing tuberculosis or leprosy. Notably, the Mycobacterium avium complex (MAC) is the most frequent cause of NTM infections. Despite being relatively rare, the incidence of NTM-PD is growing globally, with around 130,000 cases reported in the U.S. and Europe combined, increasing at an annual rate of 8%. Patients suffering from NTM lung disease face chronic symptoms, progressive lung damage, and a significantly reduced quality of life, prompting the need for better treatment options.

The Phase 1 study focused on the safety and intrapulmonary PK of SPR719, including its concentrations in pulmonary epithelial lining fluid (ELF) and alveolar macrophages (AM). Conducted as a single-center, open-label study, it involved healthy adult male and female volunteers who received a daily dose of 1,000 mg of SPR720 for seven days. The study's safety population included 33 subjects, while the PK population comprised 30 subjects.

During the trial, blood samples were collected for plasma pharmacokinetic assessments, and each participant underwent a standardized bronchoscopy and bronchoalveolar lavage (BAL) on the final day. The study found no significant concentrations of SPR720 in the plasma. However, the mean plasma concentrations of SPR719 peaked at approximately four hours post-administration and then gradually decreased over the next 24 hours.

Importantly, the concentrations of SPR719 in the ELF and AM were higher than in the plasma, suggesting significant lung uptake and enhanced presence in these compartments. This finding is critical, as effective oral therapy for NTM lung disease requires adequate drug concentrations in the pulmonary epithelial lining fluid and alveolar macrophages where the mycobacteria reside and proliferate. The study observed no unexpected safety concerns, bolstering the potential of SPR720 as an oral treatment for NTM-PD.

Sath Shukla, President and CEO of Spero, emphasized that these results are part of a broader series of studies exploring SPR720's potential as a treatment for NTM-PD. Given the significant lung uptake and enhanced ELF and AM concentrations observed, the data supports further investigation into SPR720 as a viable oral agent for NTM-PD treatment.

Additionally, data from an in vitro evaluation of microbial resistance development against SPR719 will be presented at the upcoming IDWeek conference in Los Angeles, scheduled for October 16-19, 2024.

Spero Therapeutics continues to make strides in developing novel treatments for rare diseases and multi-drug resistant bacterial infections. Its recent findings contribute to the growing body of evidence supporting SPR720's potential as an effective treatment for patients with NTM lung disease, addressing a significant unmet medical need in this field.