SPR206 / Spero Therap, Everest Medicines - LARVOL DELTA

In vitro activity of SPR206 and comparator agents against Pseudomonas aeruginosa, Acinetobacter species, and Enterobacterales responsible for infection in United States, European, Israeli, and Turkish hospitals. (PubMed, Microbiol Spectr) - "Additional treatment options are needed as antimicrobial resistance emerges and spreads. The results presented in this manuscript show potent SPR206 activity against resistant and difficult-to-treat gram-negative organisms."

Journal • Preclinical • Infectious Disease

Antibiotics and non-traditional antimicrobial agents for carbapenem-resistant Acinetobacter baumannii in Phase 1, 2, and 3 clinical trials. (PubMed, Expert Opin Investig Drugs) - "Specifically, 9 antibiotics are in Phase 1 (R-327, xeruborbactam/QPX-7728, upleganan/SPR-206, MRX-8, QPX-9003, zifanocycline/KBP-7072, apramycin/EBL-1003, zosurabalpin/RG-6006, and ANT-3310), two in Phase 2 (BV-100, OMN-6), and two in Phase 3 (zidebactam/WCK-5222, funobactam/XNW-4107) clinical trials...In particular, two monoclonal antibodies (TRL-1068, CMTX-101), a phage therapy (Phagebank), an immune-modulating agent (recombinant human plasma gelsolin/Rhu-pGSN), a microbiome-modulating agent (SER-155), and an engineered cationic antibiotic peptide (PLG-0206). Several agents with promising characteristics against CRAB infections are in clinical development (Phases 1, 2, and 3). The urgent need for therapeutic options against CRAB infections necessitates optimizing efforts and time for introducing successfully studied agents into clinical practice."

Journal • Review • Infectious Disease • GSN

The novel polymyxin analogue SPR206 exhibits higher activity than colistin against both colistin-susceptible and colistin-resistant strains of Acinetobacter baumannii. (PubMed, Antimicrob Agents Chemother) - "SPR206 exhibited higher activity against colistin-susceptible and colistin-resistant strains (MIC50/MIC90 = 0.12/0.25 mg/L), and resistance was only detected in 1/118 strains (MIC ≥4 mg/L). Mutations in pmrCAB, linked to colistin resistance, do not seem to confer resistance to the novel polymyxin, which retains a high level of activity."

Journal • Infectious Disease

Spero Therapeutics Announces Fourth Quarter and Full Year 2024 Operating Results and Provides a Business Update (GlobeNewswire) - "Together with GSK, we are conducting a pre-specified interim analysis of the Phase 3 PIVOT-PO clinical trial of tebipenem HBr. This pre-specified interim analysis is expected in Q2 2025....SPR206: The Company announced discontinuation of the SPR206 program following a reprioritization of the pipeline in Q1 2025."

Discontinued • P3 data • Infectious Disease

Enhanced antimicrobial activity of the novel polymyxin analogue SPR206 compared to colistin against colistin-susceptible and colistin-resistant Acinetobacter baumannii (ESCMID Global 2025) - No abstract available

Innovative Antibiotic Therapies for Carbapenem-Resistant Gram-Negative Bacterial Infections: Clinical Efficacy, Safety, and Comparative Studies. (PubMed, Microorganisms) - "Cefiderocol has shown superior outcomes in complicated urinary tract infections (cUTI) compared to imipenem-cilastatin. A comparison of colistin monotherapy versus combination therapy with meropenem for carbapenem-resistant infections revealed no significant improvement in clinical outcomes with combination therapy but noted delays in resistance development. Colistin-rifampicin combination therapy showed potential benefits for colistin-resistant Acinetobacter baumannii, although results were not statistically significant. SPR206, a polymyxin derivative, and durlobactam, a β-lactamase inhibitor, show promise in addressing these resistant strains, with durlobactam demonstrating efficacy in combination with sulbactam and imipenem-cilastatin. Additional studies investigated antibiotic strategies for resistant infections, including cefoperazone-sulbactam versus combination therapy with tigecycline, and examined infection-prevention strategies in surgical settings, comparing..."

Journal • Review • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

Potentially effective antimicrobial treatment for pneumonia caused by isolates of carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii complex species: what can we expect in the future? (PubMed, Expert Rev Anti Infect Ther) - "Doubling the routine intravenous maintenance dosages of conventional tigecycline (100 mg every 12 h) and minocycline (200 mg every 12 h) might be recommended for the effective treatment of pneumonia caused by CR/XDR-Abc. Nebulized polymyxin E, novel parenteral rifabutin BV100, and new polymyxin derivatives (SPR206, MRX-8, and QPX9003) could be considered supplementary combination options with other antibiotic classes. Regarding other novel antibiotics, the potency of sulbactam-durlobactam (1 g/1 g infused over 3 h every 6 h intravenously) combined with imipenem-cilastatin, and the β-lactamase inhibitor xeruborbactam, is promising. Continuous infusion of full-dose cefiderocol is likely an effective treatment regimen for CR/XDR-Abc pneumonia. Zosurabalpin exhibits potent anti-CR/XDR-Abc activity in vitro, but its practical use in clinical therapy remains to be evaluated. The clinical application of antimicrobial peptides and bacteriophages requires validation."

Journal • Review • Infectious Disease • Pneumonia • Respiratory Diseases

Pharmacokinetics and safety of EVER206, a novel polymyxin antimicrobial, in healthy Chinese subjects. (PubMed, Antimicrob Agents Chemother) - "The exposure of EVER206 in Chinese healthy subjects was higher than that in Australian healthy subjects. These results could enable further clinical development of EVER206 in Chinese patients with severe MDR Gram-negative pathogen infections.CLINICAL TRIALSThis study was registered at the Chinese Clinical Trial Registry under identifier ChiCTR2200056692."

Clinical • Journal • PK/PD data • Infectious Disease

SPR206: a novel polymyxin with broad-spectrum Gram-negative efficacy has potent synergy with macrolide and tetracycline antibiotics (ECCMID 2024) - No abstract available

Clinical • Gram negative • Infectious Disease

Pharmacokinetics/pharmacodynamics and safety of EVER206, a novel polymyxin antimicrobial, in healthy Chinese subjects (ECCMID 2024) - No abstract available

Clinical • PK/PD data

Determining Susceptibility and Potential Mediators of Resistance for the Novel Polymyxin Derivative, SPR206, in Acinetobacter baumannii. (PubMed, Antibiotics (Basel)) - "With the increase in carbapenem-resistant A. baumannii (CRAB) infections, there has been a resurgence in the use of polymyxins, specifically colistin (COL). Finally, SPR206-based combination regimens exhibited increased synergistic and bactericidal activity compared with COL-based combination regimens irrespective of the multiple resistance genes detected. The results of this study highlight the potential utility of SPR206 in the treatment of COL-resistant A. baumannii infections."

Journal • Infectious Disease

Novel drug candidates against antibiotic-resistant microorganisms: A review. (PubMed, Iran J Basic Med Sci) - "This review focuses on the resistance mechanisms of the top five threatening pathogens identified by the World Health Organization's global priority pathogens list: carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin, vancomycin-resistant Staphylococcus aureus...The novel drugs against carbapenem-resistant bacteria include LCB10-0200, apramycin, and eravacycline, while for Enterobacteriaceae, the drug candidates are LysSAP-26, DDS-04, SPR-206, nitroxoline, cefiderocol, and plazomicin. TNP-209, KBP-7072, and CRS3123 are agents against E. faecium, while Debio 1450, gepotidacin, delafloxacin, and dalbavancin are drugs against antibiotic-resistant S. aureus. In addition to these identified drug candidates, continued in vitro and in vivo studies are required to investigate small..."

Journal • Review

Safety and pharmacokinetics of SPR206 in subjects with varying degrees of renal impairment. (PubMed, Antimicrob Agents Chemother) - "SPR206 was excreted in urine within 12 h in healthy subjects and subjects with mild RI (Cohort 2) but was prolonged in those with moderate and severe RI (Cohorts 3 and 4, respectively). In summary, SPR206 was generally safe and well tolerated, and the PK of SPR206 was well characterized in subjects with RI."

Journal • PK/PD data • Chronic Kidney Disease • Infectious Disease • Nephrology • Pneumonia • Renal Disease

Safety and Pharmacokinetics of SPR206 in Subjects with Varying Degrees of Renal Impairment (IDWeek 2023) - No abstract available

Clinical • PK/PD data • Infectious Disease

Pharmacokinetics of SPR206 in Plasma, Pulmonary Epithelial Lining Fluid, and Alveolar Macrophages following Intravenous Administration to Healthy Adult Subjects. (PubMed, Antimicrob Agents Chemother) - "The most frequent TEAEs were oral paresthesia (10 subjects [29.4%]) and nausea (2 subjects [5.9%]). This study demonstrates pulmonary penetration of SPR206 and supports further development of SPR206 for the treatment of patients with serious infections caused by MDR Gram-negative pathogens."

Journal • PK/PD data • Infectious Disease

In Vivo Pharmacodynamic Profile of EVER206, a Novel Polymyxin Antimicrobial, against Gram-Negative Bacteria in the Murine Thigh Infection Model. (PubMed, Antimicrob Agents Chemother) - "Mice were pretreated with cyclophosphamide (induce neutropenia) and uranyl nitrate (increase the exposure of test compound through predictable renal dysfunction). Using the murine thigh model, the fAUC/MIC targets of EVER206 were assessed across a broad MIC distribution. Integrating these data with microbiologic and clinical exposure data will aid in determining the clinical dose of EVER206."

Gram negative • Journal • PK/PD data • Preclinical • Hematological Disorders • Infectious Disease • Nephrology • Neutropenia • Pneumonia • Renal Disease

Activity of SPR206 and comparator agents against Pseudomonas aeruginosa and Acinetobacter baumannii causing infections in Europe and adjacent regions (ECCMID 2023) - No abstract available

Infectious Disease

In vitro activity of SPR206 and comparator compounds against Enterobacterales isolates responsible for infections in hospitals in Europe and adjacent Regions (ECCMID 2023) - No abstract available

Preclinical • Infectious Disease

"We need Antibiotics for CRAB , but Polymyxins, again ? 🆕️⚡️ @antibioticsmdpi @AbdullahTarikA1 @davidantibiotic et Al Next-Generation Polymyxin Class of Antibiotics: A Ray of Hope Illuminating a Dark Road SPR206, MRX-8, and 📍QPX9003📍,others ? https://t.co/zUVaJK4Ffa" (@ABsteward)

SPR206 Pharmacokinetics (PK) in Plasma, Epithelial Lining Fluid (ELF), and Alveolar Macrophages (AM) in Healthy Adult Subjects (IDWeek 2022) - No abstract available

Clinical • PK/PD data • Infectious Disease

Combination Therapy for the Investigational Polymyxin SPR206 and Meropenem (MEM) Increases the Rapidity and Extent of Killing of Pseudomonas aeruginosa (PA) and Prevents the Bacterium from Emerging Resistant to Both Antibiotics (IDWeek 2022) - No abstract available

Combination therapy • Infectious Disease

In vitro Activity of SPR206 and Comparator Compounds against Enterobacterales Isolates Responsible for Infections in United States Hospitals (IDWeek 2022) - No abstract available

Preclinical • Infectious Disease

Activity of SPR206 and Comparator Agents Against Pseudomonas aeruginosa and Acinetobacter baumannii Causing Infections in United States Hospitals (IDWeek 2022) - No abstract available

Clinical • Infectious Disease

Spr206, a Novel Polymyxin with Gram-Negative Coverage, Remediates Acinetobacter Baumannii Infections In Vivo (ASM Microbe 2022) - "We have identified SPR206 as a drug candidate for potentially broad clinical indications. The results of the lung and wound models suggest that this compound could be efficacious in a hospital acquired bacterial pneumonia clinical scenario, as well as a wound infection setting for treatment of acute bacterial skin and skin structure infection. SPR206 is a potent, new polymyxin for expanded clinical use against Gram-negative pathogens."

Preclinical • Infectious Disease • Pneumonia • Respiratory Diseases • Septic Shock

REMOTE SPEAKER - In Vivo Pharmacodynamic Profile of EVER206, a Next Generation Polymyxin, Against Gram-Negative Bacteria in the Murine Thigh Infection Model (ASM Microbe 2022) - " PSA (n=10), EC (n=9), ECL (n=2), Enterobacter (now Klebsiella) aerogenes (EA) (n=1), and KP (n=5) were assessed including meropenem-resistant (n=13) and cefepime-resistant (n=16) isolates...Mice were pretreated with cyclophosphamide to induce neutropenia and uranyl nitrate to yield a predictable degree of renal impairment to produce more humanized PK... The present study evaluated the fAUC/MIC targets of EVER206 across a broad MIC distribution in murine thigh efficacy models. These data integrated with the microbiologic and clinical exposure data will aid in determining the clinical dose of EVER206."

PK/PD data • Preclinical • Hematological Disorders • Infectious Disease • Neutropenia • Pneumonia • Renal Disease • Respiratory Diseases