Spero Therapeutics Announces Positive Topline Results From Phase 1 Bronchoalveolar Lavage Clinical Trial 

Spero Therapeutics, Inc. recently announced topline findings from its Phase 1 bronchoalveolar lavage (BAL) clinical trial of SPR206, an intravenously (IV)-administered next-generation polymyxin product candidate. SPR206 was derived from Spero’s potentiator platform and is in development to treat serious multi-drug resistant (MDR) gram-negative infections in the hospital setting.

The Phase 1 BAL study evaluated the safety and pharmacokinetics (PK) of SPR206 when administered at 100 mg, three times daily. Results showed that SPR206 was generally well-tolerated with a mean lung epithelial lining fluid (ELF) to plasma concentration ratio of 0.264, with area under the curve (AUC) from 0-8 hours used to estimate the total uptake of SPR206. Importantly, the mean concentration of SPR206 in the lung ELF exceeds the SPR206 MIC (minimum inhibitory concentration) for targeted gram-negative pathogens for the entirety of the 8-hour dosing period.

“Many of the patients we hope to serve suffer from extensive drug-resistant bacterial lung infections with fewer treatment options available to them each day,” said David Melnick, MD, Chief Medical Officer of Spero Therapeutics. “These promising results show that SPR206 achieves concentrations in lung epithelial lining fluid which may be sufficient to advance the development of SPR206 into clinical trials of patients with serious life-threatening pulmonary infections.”

“SPR206 has achieved an important milestone, as these data support our belief that SPR206 has the potential to offer therapeutic activity against MDR gram-negative lung infections,” said Ankit Mahadevia, MD, Chief Executive Officer of Spero. “Together with our prior Phase 1 and preclinical data, we look forward to engaging with regulators as we plan the continued development of SPR206.”

The Phase 1 BAL clinical trial was an open-label study designed to enroll 30 healthy volunteers into five cohorts. Subjects received three 100 mg doses of SPR206 infused every eight hours over one day. The objectives of the study were to evaluate the intrapulmonary pharmacokinetics (PK), including epithelial lining fluid (ELF) and alveolar macrophage (AM) concentrations of SPR206 compared to plasma concentrations to establish dose requirements for clinical efficacy of SPR206 in the setting of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP). This study was conducted in collaboration with, and with financial support from, the US Department of Defense (Award No. W81XWH1910295).

SPR206 is an IV-administered next generation polymyxin product candidate designed to act directly on Gram-negative bacterial infections through the molecule’s interactions with the bacterial outer membrane. In preclinical studies, SPR206 has demonstrated potent broad-spectrum activity against Gram-negative bacteria, including organisms identified by the Centers for Disease Control and Prevention and the World Health Organization as urgent and serious threats to human health. Spero has completed a first-in-human Phase 1 assessment of SPR206 in which the product candidate was generally well tolerated and demonstrated no evidence of nephrotoxicity at anticipated therapeutic doses. A Phase 1 bronchoalveolar lavage (BAL) clinical trial assessing the penetration of SPR206 into the pulmonary compartment has been completed and a Phase 1 renal impairment clinical trial of SPR206 is ongoing. For more information on these trials and their design, see ClinicalTrials.gov identifiers NCT04868292 (BAL trial) and NCT04865393 (renal impairment trial). SPR206 has been granted Qualified Infectious Disease Product (QIDP) designation by the USFDA for the treatment of complicated urinary tract infections and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).

SPR206 clinical trials have been supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Joint Warfighter Medical Research Program under Award No. W81XWH1910295. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. The U.S. Army Medical Research Acquisition Activity, 839 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office.

Spero Therapeutics, Inc. is a multi-asset, clinical-stage biopharmaceutical company focused on identifying, developing and commercializing novel treatments for MDR bacterial infections and rare diseases. Spero’s lead product candidate, tebipenem HBr (tebipenem pivoxil hydrobromide; formerly SPR994), is being developed as the first oral carbapenem antibiotic for use in cUTI, including pyelonephritis. On January 3, 2022, Spero announced that the FDA has accepted its NDA for tebipenem HBr tablets. Tebipenem HBr is an investigational drug in the US and is currently not approved for the treatment of complicated urinary tract infection, including pyelonephritis.

Spero is also developing SPR720 as a novel oral therapy product candidate for the treatment of a rare, orphan pulmonary disease caused by non-tuberculous mycobacterial infections. Spero also has an IV-administered next generation polymyxin product candidate, SPR206, developed from its potentiator platform, which is being developed to treat MDR Gram-negative infections in the hospital setting. For more information, visit https://sperotherapeutics.com.