Amphoraxe is developing replacements for conventional antibiotics that are based on antimicrobial peptides (AMPs). AMPs are short host defense proteins that all living organisms produce naturally as part of their immune systems. Our lead candidates can kill many different kinds of 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 kill 10 million people a 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 food-borne 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 looking for 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. As a result, they do not induce resistance to the same degree as conventional antibiotics. Further, AMPs used in the agricultural sector would be broken down in farm animals' bodies and would not persist in the meat or eggs, nor in 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 perform safety tests. Farm trials of our lead candidates will begin in 2021.
AMPs are produced by all living organisms. Our pipeline is based on rich databases of genome sequences and does not require expensive, specialised proteomics approaches. Our ability to identify new AMPs is limited only by the genome sequences available to us – and plans to sequence the genomes of all ~1.5 million species on earth within a decade are already underway.