SPR720 / Spero Therap - LARVOL DELTA

Pyrimidine-Based Compounds in Tuberculosis Management: A Review of their Biological and Medicinal Importance. (PubMed, Med Chem) - "Three medications-GSK-286, TBA- 7371, and SPR-720 are now undergoing clinical testing. This study aims to emphasize the structural variety of anti-tuberculosis pyrimidine-containing compounds by providing an overview of current developments in drug discovery investigations."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SPR720 as Compared With Placebo for the Treatment of Participants With Mycobacterium Avium Complex (MAC) Pulmonary Disease (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: Spero Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

Intrapulmonary pharmacokinetics of SPR719 following oral administration of SPR720 to healthy volunteers. (PubMed, Antimicrob Agents Chemother) - P1 | "Results from this study of the intrapulmonary disposition of SPR719 support further investigation of SPR720 as a potential oral agent for the treatment of patients with NTM-PD. This study is registered with ClinicalTrials.gov as NCT05955586."

Journal • PK/PD data • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SPR720 as Compared With Placebo for the Treatment of Participants With Mycobacterium Avium Complex (MAC) Pulmonary Disease (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: Spero Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

A Study to Assess the Intrapulmonary Pharmacokinetics (PK) of SPR719 by Comparing the Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations Following the Oral Administration of Multiple Doses of SPR720 in Healthy Volunteers. (clinicaltrials.gov) - P1 | N=33 | Completed | Sponsor: Spero Therapeutics | Recruiting ➔ Completed

Trial completion

A Study to Evaluate the Effect of Co-administration on the Pharmacokinetics of SPR720, Azithromycin, and Ethambutol in Healthy Participants (clinicaltrials.gov) - P1 | N=39 | Completed | Sponsor: Spero Therapeutics | Trial completion date: Oct 2023 ➔ Feb 2024 | Trial primary completion date: Oct 2023 ➔ Jan 2024

Trial completion date • Trial primary completion date

Efficacy of SPR720 in murine models of non-tuberculous mycobacterial pulmonary infection. (PubMed, J Antimicrob Chemother) - "In vitro activity of SPR720 against common NTM pathogens and efficacy in murine infections warrant the continued clinical evaluation of SPR720 as a new oral option for the treatment of NTM-PD."

Journal • Nontuberculous mycobacteria • Preclinical • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SPR720 as Compared With Placebo for the Treatment of Participants With Mycobacterium Avium Complex (MAC) Pulmonary Disease (clinicaltrials.gov) - P2 | N=35 | Recruiting | Sponsor: Spero Therapeutics | Trial completion date: Nov 2023 ➔ Oct 2024 | Trial primary completion date: Nov 2023 ➔ Oct 2024

Trial completion date • Trial primary completion date • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

Nontuberculous mycobacterial pulmonary disease and the potential role of SPR720. (PubMed, Expert Rev Anti Infect Ther) - "Treatment guidelines for Mycobacterium avium complex (MAC) pulmonary disease involve a three-drug regimen with azithromycin, ethambutol, and rifampin, and those of Mycobacterium abscessus complex (MAB) pulmonary disease involve a combination of three or more antimicrobials including macrolides, amikacin, and a β-lactam or imipenem. The current antimicrobial management options for NTM-PD are limited in number and there exists a large unmet need for new treatments. SPR720 has encouraging data that warrant further study in the context of a multidrug regimen."

Journal • Nontuberculous mycobacteria • Gastrointestinal Disorder • Nontuberculous Mycobacterial Disease • Pain • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate the Effect of Co-administration on the Pharmacokinetics of SPR720, Azithromycin, and Ethambutol in Healthy Participants (clinicaltrials.gov) - P1 | N=33 | Completed | Sponsor: Spero Therapeutics | Recruiting ➔ Completed

Trial completion

A Study to Assess the Intrapulmonary Pharmacokinetics (PK) of SPR719 by Comparing the Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations Following the Oral Administration of Multiple Doses of SPR720 in Healthy Volunteers. (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Spero Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Evaluate the Effect of Co-administration on the Pharmacokinetics of SPR720, Azithromycin, and Ethambutol in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Spero Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Evaluate the Effect of Co-administration on the Pharmacokinetics of SPR720, Azithromycin, and Ethambutol in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Spero Therapeutics

New P1 trial

A Study to Assess the Intrapulmonary Pharmacokinetics (PK) of SPR719 by Comparing the Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations Following the Oral Administration of Multiple Doses of SPR720 in Healthy Volunteers. (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Spero Therapeutics

New P1 trial

A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SPR720 as Compared With Placebo for the Treatment of Participants With Mycobacterium Avium Complex (MAC) Pulmonary Disease (clinicaltrials.gov) - P2 | N=31 | Recruiting | Sponsor: Spero Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

Pyrimidine derivatives with antitubercular activity. (PubMed, Eur J Med Chem) - "Small molecules with antitubercular activity containing the pyrimidine motif in their structure have gained more attention after three drugs, namely GSK 2556286 (GSK-286), TBA-7371 and SPR720, have entered clinical trials. In the first part, the review discusses the pyrimidine compounds according to their targets, pinpointing the structure-activity relationships of each pyrimidine family. The second part of this review is concentrated on antitubercular pyrimidine derivatives with a yet unexplored or speculative target, dividing the compounds according to their structural types."

Journal • Review • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of SPR720 as Compared With Placebo for the Treatment of Participants With Mycobacterium Avium Complex (MAC) Pulmonary Disease (clinicaltrials.gov) - P2 | N=31 | Not yet recruiting | Sponsor: Spero Therapeutics

New P2 trial • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

"$SPRO Announces Immediate Cessation of Tebipenem HBr Commercialization Initiatives. Company to Shift Focus to Advancement of SPR720 and SPR20 https://t.co/Gg20M0SkVb" (@BioStocks)

In Vitro Resistance against DNA Gyrase Inhibitor SPR719 in Mycobacterium avium and Mycobacterium abscessus. (PubMed, Microbiol Spectr) - "Here, we characterized in vitro resistance against SPR719, a drug candidate for the treatment of lung disease caused by non-tuberculous mycobacteria (NTM). The identified resistance associated mutations and the observed differential resistance behavior of the two characterized NTM species provide a basis for follow-up studies of resistance in vivo to further inform clinical development of SPR719."

Journal • Preclinical • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

First-in-Human Evaluation of the Safety, Tolerability, and Pharmacokinetics of SPR720, a Novel Oral Bacterial DNA Gyrase (GyrB) Inhibitor for Mycobacterial Infections. (PubMed, Antimicrob Agents Chemother) - "However, plasma AUC was comparable between Days 7 and 14. Results of this first-in-human study suggest that predicted therapeutic exposures of SPR719 can be attained with a once-daily oral administration of SPR720."

Clinical • Journal • P1 data • PK/PD data • Gastrointestinal Disorder • Infectious Disease • Nontuberculous Mycobacterial Disease • Pain • Pulmonary Disease • Respiratory Diseases • Tuberculosis

In vitro activity of SPR719 against Mycobacterium ulcerans, Mycobacterium marinum and Mycobacterium chimaera. (PubMed, PLoS Negl Trop Dis) - "We show that SPR719 is active against these NTM species with a MIC range of 0.125-4 μg/ml and that this compares favorably with the commonly utilized antimycobacterial antibiotics, rifampicin and clarithromycin. Our findings suggest that SPR720 should be further evaluated for the treatment of NTM infections."

Journal • Preclinical • Infectious Disease • Respiratory Diseases • Tuberculosis

[VIRTUAL] Characterization of Resistance to DNA Gyrase Inhibitor SPR719 in Mycobacterium avium (WMF 2021) - "Recently, the aminobenzimidazole SPR720 entered development for the treatment of M. avium disease...Moxifloxacin and clarithromycin, included as comparators, yielded similar frequencies of resistance of ~10-8/CFU...In conclusion, in vitro resistance analyses of SPR719 in M. avium revealed a frequency of resistance of 10-9 to 10-8/CFU and associated polymorphisms mapped to the ATPase domain of the GyrB subunit of DNA gyrase. These results demonstrate a low propensity for the development of resistance and confirm the mechanism of action of the novel DNA gyrase inhibitor in M. avium."

Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

Phase 2a Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease (clinicaltrials.gov) - P2a; N=2; Terminated; Sponsor: Spero Therapeutics; N=90 ➔ 2; Trial completion date: Feb 2022 ➔ Jan 2021; Suspended ➔ Terminated; Trial primary completion date: Jan 2022 ➔ Jan 2021; Business decision pending resolution of clinical hold with FDA

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Respiratory Diseases

Phase 2a Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease (clinicaltrials.gov) - P2a; N=90; Suspended; Sponsor: Spero Therapeutics; Recruiting ➔ Suspended

Clinical • Trial suspension • Respiratory Diseases

The benzimidazole SPR719 shows promising concentration-dependent activity and synergy against nontuberculous mycobacteria. (PubMed, Antimicrob Agents Chemother) - "We recorded potential for combination therapy with ethambutol against M. kansasii and M. avium and synergy with clarithromycin against M. abscessus Ethambutol increased the SPR719 kill rate against M. kansasii but only prevented SPR719 resistance in M. aviumSPR719 is active in vitro against NTM; its activity is strongest against M. kansasii, followed by MAC and M. abscessus SPR719 shows promise for combination therapy with ethambutol against MAC and M. kansasii and synergy with clarithromycin against M. abscessus The parent drug SPR720 could have a role especially in MAC pulmonary disease treatment. Further studies in dynamic models and trials are ongoing to advance clinical development."

Journal • Nontuberculous Mycobacterial Disease • Respiratory Diseases