Motif Bio plc (LON:MTFB), a clinical stage biopharmaceutical company specialising in developing novel antibiotics, announced today that new pre-clinical data with its investigational drug candidate iclaprim were presented today during the IDWeek 2017™ conference, held in San Diego, CA, 4-8 October 2017.
Efficacy Evaluation of Iclaprim in a Neutropenic Rat Lung Infection Model with Methicillin-Resistant Staphylococcus aureus Entrapped in Alginate Microspheres
David Huang, M.D., Ph.D., Chief Medical Officer of Motif Bio, presented data from an in vivo study evaluating the therapeutic potential of iclaprim in methicillin-resistant Staphylococcus aureus (MRSA) lung infections. In an in vivo model mimicking the pathophysiology observed in patients with cystic fibrosis, rats received either iclaprim 80 mg/kg (n=16), iclaprim 60 mg/kg (n=16), vancomycin 50 mg/kg (n=24) or placebo (n=29). Regardless of dose, the iclaprim-treated rats demonstrated 100% survival (33/33), while the vancomycin group demonstrated 91.7% survival (22/24) and the control group showed 48.3% survival (14/29). In addition to the improved survival rates, iclaprim treatment resulted in a significantly greater reduction in bacterial colony forming units (CFUs) compared to vancomycin (iclaprim 80 mg/kg vs vancomycin: p=0.0002; iclaprim 60 mg/kg vs vancomycin: p=0.05).
Dr Huang commented: “Following the recently announced positive, top-line Phase 3 REVIVE-2 clinical trial results for iclaprim for acute bacterial skin and skin structure infections (ABSSSI), the data presented today at IDWeek underscore the potential utility of iclaprim in a range of patient populations with suspected MRSA infections, including cystic fibrosis patients with Staphylococcus aureus lung infections. Staphylococcus aureus is a common cause of pneumonia in patients with cystic fibrosis and we do not believe that any antibiotic has been approved for this indication. Some 80% or more of patients with cystic fibrosis die as a result of respiratory infections caused by a variety of bacteria, and MRSA infections have been growing in recent years. The encouraging new data presented today support developing iclaprim as a potential treatment option for MRSA infections in patients with cystic fibrosis, and iclaprim was recently granted Orphan Drug Designation in the U.S. for Staphylococcus aureus lung infections in this patient group.”
Effects of Iclaprim and Trimethoprim on Exotoxin Production by Methicillin-Resistant Staphylococcus aureus.
Amy Bryant, PhD, VA Medical Center, Boise, ID presented data from an in vitro study evaluating the effects of sub-inhibitory doses of dihydrofolate reductase inhibitors (iclaprim and trimethoprim), compared to cell wall-active agents (nafcillin, vancomycin) on the exotoxin production from two clinical MRSA isolates. Exotoxins such as alpha-hemolysin (AH) and Toxic shock syndrome toxin 1 (TSST-1) mediate the development of disease, and inhibition of toxin production is an important consideration in choosing appropriate treatments for MRSA infections. Vancomycin is recommended for severe MRSA infections; however, increasing vancomycin resistance, poor clinical outcomes and kidney toxicity are serious concerns. The results, showed that iclaprim and trimethoprim delayed the onset of mRNA production, suppressed AH production, and delayed maximal TSST-1 in two community-acquired MRSA strains.
Dr. Huang, Chief Medical Officer of Motif Bio plc said: “Toxin suppression is an important therapeutic goal for severe infections due to toxin-producing Gram-positive pathogens such as MRSA. The in vitro data presented show that Iclaprim, at concentrations below those that inhibit bacterial growth, suppress toxin production. Iclaprim is 15-fold more active than trimethoprim, supporting the use of iclaprim to treat serious MRSA infections in hospitalised patients.”
