Grove Biopharma launches to develop therapeutic protein-like polymers

Grove Biopharma has raised a $30 million series A round to develop Bionic Biologics, also known as protein-like polymers (PLP), which were invented by Nathan Gianneschi at Northwestern University.

A PLP is a polymer of peptides that mimics a protein but is more stable and more cell permeable. It is composed of a hydrophobic, semiflexible backbone and hydrophilic ends. That structure causes the PLP to fold in on itself in an aqueous solution, mimicking a globular protein. According to Gianneschi, this property confers resistance to proteolytic degradation. But the polymer’s semiflexible, lipophilic backbone allows it to pass through cell membranes via passive diffusion, making PLPs ideal for targeting protein-protein interactions in the cell cytosol because they are not trapped in an endosome upon entry.

“Small molecules are really good at inhibiting enzymes or binding to specific pockets on proteins,” says Grove CEO Geoffrey Duyk. But he adds that to handle protein-protein interactions, “as Nathan likes to say, we need protein-scale solutions for protein-scale problems.”

One of the protein-protein interactions Grove is targeting is between Keap1 and NRF2, a pair of proteins involved in the stress response in cardiomyocytes after a heart attack. NRF2 has a protective effect against oxidative stress, but in normal circumstances, Keap1 binds to it and marks it for degradation. When more NRF2 is needed, such as after a traumatic event like a heart attack, Grove’s PLPs can bind to Keap1, stopping it from binding to NRF2 and allowing that protein to protect the cell from oxidative stress. Grove published a paper in Advanced Materials proving this concept in vivo today (DOI: 10.1002/adma.202417885).

Duyk says Grove will focus primarily on cancer for its clinical candidates. The firm is developing an androgen receptor degrader for treatment-resistant prostate cancer and an inhibitor for RAS, a notorious oncogene. Grove says it will be working on identifying specific drug candidates over the next 12–18 months.