Adapsyn Bioscience is a chemical bioinformatics company that discovers and develops novel small molecule therapeutics. The company was spun out of McMaster University in Hamilton, Ontario, in 2016 based on an early collaboration with Pfizer. More recently, Adapsyn announced a collaboration with Evotec SE and funding from the Bill & Melinda Gates Foundation. Adapsyn is backed by Genesys Capital, Pfizer Ventures, and other private investors.
The company is focused on the discovery and development of novel drug-like small molecules from microbes. Traditional methods for the identification, isolation, and testing of microbial metabolites are labor-intensive, frequently leading to the rediscovery of known compounds and often detecting only the most overt cytotoxin produced by the microbe. The first wave of “genome mining” technologies was also largely unsuccessful due to limited throughput and reliance on a technique called heterologous gene expression. As a result of these challenges, natural product research was largely deprioritized over the past 20 years in favor of combinatorial chemistry, fragment-based discovery, and DNA-encoded library approaches to small molecule discovery. This decline has coincided with an explosion of knowledge in the molecular drivers of human disease and infection. As a result, this class of chemistry has largely been ignored in the hunt for new therapeutics against emerging targets. Moreover, we now have a much better understanding of how microbes make small molecules and how they can be linked to specific biological activity.
Adapsyn’s platform analyzes metabolomic and genomic data from microbes to identify, isolate, characterize, and assay novel drug-like molecules, and the company has established the capability to screen thousands of compounds per year. The platform can identify gene clusters that encode small molecules that target specific proteins and can evaluate a molecule’s potential to be developed as a therapeutic based on our analysis of the gene cluster alone. The technology can be used to find new drugs in the fields of oncology; bacterial, fungal, and viral infections; autoimmune disorders; cardiovascular and lipid metabolism disorders; neuroscience; and other indications. In partnership with other companies, Adapsyn has also been using the platform to explore the microbiome, and for select applications in agriculture, food, and nutrition.
The biosynthetic gene clusters (BGCs) that encode the enzymes responsible for producing small molecules are often co-localized and co-expressed with bacterial self-resistance genes that protect the producing organism from the bioactivity of the molecule. Adapsyn has developed the ability to search molecular targets for self-resistance gene matches associated with novel BGCs. Using this approach, the company has identified bacterial strains containing BGCs associated with self-resistance genes matched to established and emerging targets in Mycobacterium tuberculosis, the microorganism responsible for tuberculosis. With funding from the Bill & Melinda Gates Foundation, Adapsyn is working with leading academics to evaluate a focused library of small molecule candidates for development as novel therapeutics for tuberculosis. Notably, this approach can be applied far more broadly, including to antibiotic-resistant priority pathogens identified by Health Canada and the WHO as growing threats to global health.
Despite technological advances in antibiotic discovery and increased recognition of the threat antibiotic resistance and pandemics pose to society, traditional funding models for the discovery, development, and reimbursement do not readily apply to novel anti-infectives. Put simply, increased antibiotic use can foment resistance to that specific compound, and as a result, novel therapeutics that can overcome antibiotic resistance are used sparingly. As such, novel antibiotics do not generate significant revenue, making it difficult for traditional investors and pharmaceutical companies to generate a financial return on antibiotic discovery and development.
Non-profit efforts, such as CARB-X (a global consortium of governments and foundations), the Bill & Melinda Gates Foundation, and the Innovative Medicines Initiative, have stepped up to fund the global discovery and development gap. In September 2022, BIOTECanada convened the BIONATION policy forum in Ottawa and welcomed Jean-Yves Duclos, Minister of Health. Minister Duclos’ remarks highlighted pandemic preparedness and antimicrobial resistance as a priority for the Federal government. A funding mechanism dedicated to the discovery and development of novel antibiotics and a comprehensive reimbursement strategy for novel antibiotics brought to market would support more innovation and ultimately better protect Canadians from the threat of antimicrobial resistance. Until such a mechanism is established, Canadian companies working to solve these problems will continue to rely on foreign funding sources to undertake this important work.
Beyond antibiotics, Adapsyn is focused on discovering novel therapeutics for emerging intracellular targets, including those implicated in tumorigenesis, tumor progression, and cancer metabolism. The company recently announced a screening collaboration with Evotec SE, under which they will screen novel chemical libraries discovered against high-value targets for internal projects and external partners. Adapsyn is also actively collaborating with companies in agriculture and food & nutrition to discover and characterize novel compounds for a range of applications.
Adapsyn’s approach to small molecule discovery from microbes represents a major technological advancement over traditional natural product discovery methods. Because these historic methods failed to keep pace with our rapidly evolving understanding of human disease, the full potential of this class of chemistry has yet to be realized. The company’s discovery platform combines the power of bioinformatics, genomics, and metabolomics to identify novel drug-like molecules from microbes in high throughput. With the support of strategic partnerships and funding from venture capital firms and non-profit organizations, Adapsyn is well-positioned to continue driving innovation in the field of small molecule drug discovery and developing much-needed therapeutics for patients worldwide.