Roche unit Genentech has signed an approximately $1bn alliance with Lodo Therapeutics to delve into the genomes of microbes in soil in the hope of finding new drug therapies.
The agreement is the first big pharma deal signed to date by Lodo, which only came out of stealth mode in 2016 with $17m in backing from Accelerator Life Science Partners. It includes an undisclosed upfront payment and up to $969m in R&D and commercial milestones, as well as tiered royalties on sales if products reach the market. For now, the disease categories being pursued under the alliance haven’t been divulged.
A large proportion of drugs developed in the last few decades have originated in natural products, and in particular microorganisms and plants. For example, an estimated three quarters of cancer drugs since the 1980s were derived this way, as well as a sizeable slice of drugs used to treat infections and chronic illnesses such as type 2 diabetes.
More recently, an increased focus on biologic large-molecule drugs, as well as synthetic small-molecules based on rational design and combinatorial chemistry has pegged back investment in this area, but the latest deal shows there is still interest in breaking into nature’s medicine chest.
Under the terms of the Genentech deal, Lodo will deploy its genome mining and biosynthesis expertise – drawn from the research of co-founder Sean Brady who heads up Rockefeller University’s Laboratory of Genetically Encoded Small Molecules in New York – to seek out naturally-occurring small molecules with therapeutic potential from microbial DNA.
Lodo launched just over two years ago on the strength of a platform that differs from other natural drug discovery systems; it does not rely on culturing known strains of bacteria, and focuses instead on isolating microbial DNA from soil samples and identifying gene clusters involved in the synthesis of bioactive molecules. It’s estimated that every gram of soil will contain at least 1,000 bacterial species.
The approach increases the number and diversity of natural products that are available for screening, as the majority of bacteria aren’t easy to culture in the lab, and according to Lodo could reduce the time and cost of drug discovery.
Brady’s lab work has already resulted in some interesting drug leads, including a new class of antibiotics dubbed ‘malacidins’ that have never been described in culture-based natural product discovery but seem to be active against resistant pathogens including vancomycin-resistant enterococci (VRE and methicillin-resistant Staphylococcus aureus.