Ramoplanin™ is a glycolipodepsipeptide antibiotic that is bactericidal for many gram-positive aerobic and anaerobic bacteria, including C. difficile and has previously been evaluated in clinical development programs for both vancomycin-resistant enteroccocus (VRE) as well as the active treatment of CDI. Ramoplanin™ has been reported to also have activity against C. difficile spores, both in vitro and in an animal model. Recent in vitro work sponsored by Nanotherapeutics has confirmed that effect which seems to not be sporicidal per se. The mechanism is relatively novel in that the exosporium may be the target for Ramoplanin™ binding, permitting an “ambush” type of vegetative cell killing. The natural history of CDI, regretfully, does not end with successful treatment of the infection. Approximately 25% of patients will experience a recurrence with higher rates among older age groups as well as increasing comorbidities. These relapses are thought to be at least partially due to residual spores in the human gut in clinically cured patients. Elimination of these spores could reduce relapse rates, decreasing the risk of readmission, further treatment requirements, or adverse clinical outcomes. An innovation gap exists for a compound that can successfully reduce such relapse rates as it reduce the risk of other nosocomial infections (e.g., VRE) and add a therapeutic regimen to the current armamentarium where currently none exists. Nanotherapeutics believes that ramoplanin, based on its relatively novel mechanism of action, non-absorbable kinetics (enhanced by dosing to non-inflamed gut mucosa) and established safety profile from prior studies would fill this innovation gap.
NTI-851 (Ramoplanin™) is being developed for the targeted prophylaxis of recently treated patients with C. difficile infection (CDI) at high risk for infection relapse. Twelve phase 1 studies, two phase 2 studies (one in CDI and one in VRE) as well as one phase 3 study (in CDI) have been conducted by prior Ramoplanin™ sponsors. Nanotherapeutics is now targeting a new indication for development, relapse prevention, for Ramoplanin™ and a phase 2b study is under development with first patient in scheduled for 2016.
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