BAP5191 (Lefleuganan): An Investigational Peptide-Based Therapeutic for Cutaneous Leishmaniasis

I. Executive Summary

BAP5191, identified by DrugBank accession number DB18021, is an investigational drug primarily recognized under the name lefleuganan. It is a synthetic nonapeptide developed by the Swiss biopharmaceutical company Bacoba AG, with a primary therapeutic focus on cutaneous leishmaniasis (CL), a neglected tropical disease with significant unmet medical needs.[1] Despite its classification in DrugBank as a "Small Molecule," detailed chemical analyses reveal lefleuganan to be a peptide derivative inspired by the natural antimicrobial peptide leucinostatin A.[1]

The development of lefleuganan represents a significant advancement in medicinal chemistry, successfully modifying a highly potent but overtly toxic natural product, leucinostatin A, to retain desired antiprotozoal efficacy while substantially mitigating host toxicity. Leucinostatin A's clinical utility was previously hindered by its severe side effects, primarily linked to the inhibition of mitochondrial ATP synthase.[4] Lefleuganan, through specific structural alterations, particularly the substitution of a critical hydroxyleucine residue, exhibits a distinct primary mechanism of action. Its antiprotozoal effects are now attributed to the energetic uncoupling of negatively charged membranes, rather than direct ATP synthase inhibition, leading to a markedly improved safety profile.[4] Preclinical studies have demonstrated lefleuganan's potent antiprotozoal activity in the nanomolar range, comparable to its parent compound, but with significantly reduced acute systemic toxicity and cytotoxicity in mammalian cells.[4]