Extracellular degrader firm raises $130 million to advance into the clinic

GlycoEra is in the sweet spot, raising $130 million to advance sugar-tagged biologics that can drive the degradation of extracellular targets. A first program targeting immunoglobulin G4 (IgG4) antibodies is set to enter the clinic later this year.

“Being able to pull out disease-causing antibodies while leaving all the good antibodies is a really exciting opportunity,” says GlycoEra CEO Ganesh Kaundinya. Disease-associated antibodies are “the low-hanging fruit” for extracellular degraders, he adds, but the technology is also perfect for targeting circulating and membrane-bound proteins that are intractable for small molecules or antibodies.

GlycoEra, like others in the extracellular-protein-degrading space, is harnessing the biology of asialoglycoprotein receptors (ASGPRs) to take on these troublesome targets. ASGPRs sit on liver cells, snagging exposed sugars on circulating aging proteins and then shunting the captured molecules into protein-destroying organelles called lysosomes. By building bifunctional molecules that can bridge the gap between a target of interest and an ASGPR, drug developers hope to trick liver cells into clearing out disease-associated proteins.

GlycoEra’s molecules of choice to bring troublesome proteins to ASGPRs are antibodies and antibody fragments. It makes these in a single-celled eukaryotic organism that belongs to the Kinetoplastida family and that can tag the proteins with sugars that bind ASGPR.

Several groups have used the N-acetylgalactosamine sugar to bind ASGPR, but GlycoEra uses a different sugar moiety. “Our ASGPR engager is completely differentiated from what has been publicly disclosed by others,” Kaundinya says.

GlycoEra’s first test of its technology builds on growing enthusiasm for immunoglobulin G (IgG)–depleting therapies. Biologics that block the neonatal fragment crystallizable receptor (FcRN) have been shown to prevent antibody recycling, driving down IgG levels for the treatment of autoantibody-driven diseases. Johnson & Johnson forecasts peak annual sales of over $5 billion for its FcRN blocker nipocalimab, which the US Food and Drug Administration recently approved and which the company acquired in its $6.5 billion purchase of Momenta Pharmaceuticals, cofounded by Kaundinya.

But whereas FcRN blockers deplete all forms of the IgG antibodies, GlycoEra’s lead program GE8820 uses an antibody fragment to bind only the IgG4 isotype.

IgG4 accounts for just 5% of the total IgG protein load, adds Kaundinya, and so GE8820 should be able to drive faster and deeper degradation than a pan-IgG degrader. By sparing isotypes IgG1, IgG2, and IgG3, GE8820 should also leave patients with functioning immune systems to fight off viral infections.

The company will start a Phase 1 trial of its lead candidate in healthy volunteers later this year. Future trials will test the biologic in IgG4-associated diseases including pemphigus, muscle-specific kinase myasthenia gravis, primary membranous nephropathy, and autoimmune encephalitis.