Insects are incredible survivors. Not only have they survived for close to 400 million years, but they have done so with a low “speciation rate” as well as a low “extinction rate”; they are well-suited to their environment. Many questions surround their success; the ones surrounding their success regarding infectious diseases, however, interest Arrevus. Given their short life spans, insect rely on innate (rapid) immune response and not on adaptive responses. A critical element to the innate response are host antimicrobial peptides which are small, anti-infectious peptides released quickly to host infectious threats. Previous studies have demonstrated that in response to an experimental infection of insects, seven to ten inducible antimicrobial peptides are generated and released into insects’ circulatory system. While the antibacterial peptides made by a single insect are not homologous at all, many other species produce peptides very similar to these peptides in size and composition; the most active against Gram-negative bacteria being “proline-rich” antimicrobial peptides (PrAMPs).
The question initially posed was straightforward then: if many other species produce peptides of similar size and composition, are there amino acid residues that are conserved across species? When we designed ARV-1502, we first aligned the sequences of all known native PrAMPs in insects. The most frequent residues were identified in their specific relative positions. These residues resulted in distinct “partial” sequences that were then integrated into a single peptide, becoming Arrevus’s lead product, ARV-1502 (aka, APO; “APO” an acronym for “All Peptides Optimized”). Essentially, we are capitalizing on very slow throughput screening by nature, over millions of years, to identify peptide regions that we have integrated into compounds for use in human infectious diseases, against pathogens to which these peptides have already been optimized, through evolutionary pressure. These sequences serve as rational drug designs that leverage evolution to hopefully, limit the development of resistance, and bolster clinicians’ toolbox against the growing threat of antibiotic resistant infections.