Genentech signed a broad, open-ended drug discovery collaboration with Lodo Therapeutics that could be worth nearly $1 billion, focused on deriving unique, natural products from the microbial DNA found in soil.
The drugmaker plans to use Lodo’s metagenome-prospecting platform to identify novel small molecules with therapeutic potential against a wide range of diseases and targets. While the upfront payment was not disclosed, Lodo is eligible for development milestone bonuses totaling up to $969 million, as well as tiered royalties based on future sales.
Most of the discovery work will be conducted at Lodo’s facility in New York City, while Genentech will be largely responsible for preclinical and clinical development, said David Pompliano, Lodo’s co-founder and chief scientific officer. The companies hope the approach will reduce the overall time and cost of drug discovery, and allow for work focused on more difficult targets.
Previously, Lodo has looked to unearth molecules aimed at treating cancer, infectious diseases and inflammation. Launched just over two years ago by Accelerator Life Science Partners, the company has received support from Eli Lilly, AbbVie and Johnson & Johnson, as well as the Bill and Melinda Gates Foundation.
Lodo’s process involves collecting soil samples from around the U.S.—volunteers can send in their own in return for an Amazon gift card—which are then boiled down and analyzed for naturally occurring chemical structures that may already be known to have a biological effect, Pompliano said.
This can yield novel DNA and molecular scaffolds that have previously been too complicated to modify or manufacture synthetically, he said.
“Some of the drug targets that companies are interested in might be difficult to approach—such as protein-protein interactions that are typically difficult to drug by small molecules,” said Pompliano, who previously helped lead drug discovery efforts at Merck and GlaxoSmithKline.
“Natural products are larger and more architecturally complex molecules, so the thinking is that they would have a better chance of interfering with those types of difficult targets,” he said. The collaboration may also discover variations or analogs of products that are already available, and improve upon their pharmaceutical properties or combat drug resistance.
In addition, searching the soil allows the company to examine strains of bacteria and DNA that cannot be cultivated in a lab, allowing for a potentially huge number of overlooked new products to be explored, Pompliano said. This could include new methods of manipulation and semisynthetic products as well.
Some of these discoveries may work “out of the box,” he described, such as rapamycin, which was derived from bacteria found on Easter Island and is used to prevent the rejection of kidney transplants. Others may still need to be manipulated through other, more traditional drug development means.