Amphoraxe is developing replacements for conventional antibiotics based on antimicrobial peptides (AMPs). AMPs are short host defense proteins produced naturally by all living organisms as part of their immune systems. Our lead candidates can eliminate various bacteria, including medically important antibiotic-resistant strains, without toxicity against animal cells.

Antimicrobial Resistance - An Urgent Global Problem

Antimicrobial drugs, based on small-molecule antibiotic compounds, have saved countless lives since the discovery of penicillin in 1928. However, these drugs have now lost or are losing effectiveness as microbes become resistant. Antimicrobial resistance threatens to cause 10 million deaths per year by 2050, and to slow or even reverse modern medical advances in surgery, organ transplantation, and cancer treatment.

Antibiotics were routinely used in North American farms until recently, to keep animals healthy and protect human health by preventing foodborne illness outbreaks. The practice also had a positive effect on animal growth. In response to antimicrobial resistance, regulators in the US (2017) and Canada (2018) have restricted veterinary use of all medically important antimicrobials to prescription-only applications. These necessary changes have created an economic burden for farmers, who are seeking antibiotic replacements.

Antimicrobial Peptides as Alternatives to Conventional Small Molecule Antibiotics

Attempts to discover new small-molecule antibiotics using conventional methods have not been very successful; only 12 antibiotics have been approved since 2000, all iterations of existing drugs. No new class of antibiotics has been brought to market since daptomycin in 1986. New approaches are clearly needed.

Antimicrobial peptides are one potential alternative to conventional small-molecule antibiotics. AMPs act faster than small-molecule antimicrobials and do not cause DNA damage. Consequently, they do not induce resistance to the same degree as conventional antibiotics. Furthermore, AMPs used in the agricultural sector would be broken down in farm animals' bodies and by the enzymes in farm microbiomes, and would not persist in meat, eggs, or agricultural waste products.

AMP Discovery and Optimization at Amphoraxe

We have developed a high-throughput AMP discovery pipeline. Our computational methods identify novel AMPs from genome (DNA) sequences and use machine learning techniques to optimize the peptides for improved efficacy and safety. We then test our candidate AMPs against a range of bacterial species, including antibiotic-resistant strains, and conduct safety tests. Controlled animal trials of our lead candidates are in progress.