Spero Therapeutics to Present SPR719 In Vitro Data on Low Resistance at IDWeek 2024

In vitro data on SPR719 show low propensity for resistance development in NTM-PD MAC strains when administered as a single agent and in combination with standard of care agents.

A study highlighting the potential benefits of SPR720 for prolonged combination regimens typical to NTM-PD treatment was presented at IDWeek 2024 by Spero Therapeutics, Inc., a biopharmaceutical company focused on developing treatments for rare diseases and multi-drug resistant bacterial infections. The poster, titled “Evaluation of the Spontaneous Mutation Frequencies of SPR719 Alone and in Combination with Other Agents Used to Treat Mycobacterium avium Complex Pulmonary Disease,” was presented on October 18, 2024.

SPR720 is an oral prodrug that converts in the body to SPR719, targeting the ATPase site of DNA gyrase B in mycobacteria. This mechanism is distinct from other antibiotics used to treat nontuberculous mycobacterium pulmonary disease (NTM-PD).

The research was conducted in collaboration with Microbiologics, a contract research and manufacturing organization. Chris Pillar, Ph.D., Director of Science and Operations at Microbiologics, emphasized the significance of SPR719's activity against MAC NTM-PD. He highlighted the issue of antibiotic resistance, particularly in diseases like NTM-PD that require long treatment courses where resistance can develop. According to the data presented at IDWeek 2024, SPR719 showed high potency against both macrolide susceptible and resistant MAC strains, with a low tendency for spontaneous resistance development. These properties were maintained when SPR719 was combined with current standard care antibiotics, showing lower resistance compared to the standard care antibiotics alone.

The poster presentation highlighted several points:
- The activity of SPR719 and current standard care antibiotics (clarithromycin, ethambutol, and rifampin) was assessed for potency, the propensity for spontaneous drug-resistance development, and potential interactions for combination treatment against both macrolide susceptible and resistant MAC strains.
- SPR719 at concentrations as low as 2-fold the minimum inhibitory concentration (MIC) suppressed resistance emergence against both tested MAC isolates.
- Mutation frequencies for SPR719 were approximately 3 orders of magnitude lower than those for standard care comparators.
- SPR719 demonstrated high potency with MIC values of 2 µg/mL for both macrolide susceptible and resistant strains, and no resistant colonies emerged when combined with clarithromycin or ethambutol in the spontaneous mutation frequency assay.
- The study concluded that SPR719 had a low propensity for developing resistance and showed no antagonism when combined with clarithromycin or ethambutol, suggesting its potential for use in extended combination regimens required for NTM-PD treatment.

Nontuberculous Mycobacterium Pulmonary Disease (NTM-PD), also known as NTM lung disease, is caused by bacteria found in soil, dust, and water. These bacteria belong to the Mycobacterium family, which is distinct from tuberculosis and leprosy. The most common cause of NTM infections is the Mycobacterium avium complex (MAC). NTM is a growing global health concern with significant unmet medical needs. Although rare, the incidence of NTM pulmonary disease is increasing worldwide, affecting approximately 130,000 patients in the U.S. and Europe, with an annual growth rate of 8%. NTM lung disease leads to progressive symptoms, lung damage, and reduced quality of life due to chronic symptoms and impaired lung function. NTM infections can occur post-surgery, trauma, injections, or exposure to contaminated water. Prevention involves effective water management programs in healthcare facilities, and treatment typically requires consultation with infectious disease or pulmonary specialists. Currently, patients have limited treatment options for NTM lung disease.

Spero Therapeutics, headquartered in Cambridge, Massachusetts, is focused on developing treatments for rare diseases and multi-drug resistant bacterial infections with high unmet need.