J&J, GV back a new single-cell approach for tackling inflammatory diseases and hacking the tumor microenvironment
Most biotechs trying to tackle inflammatory disorders like IBD or attempting to boost the potency of immunotherapies for cancer have focused, logically, on targeting, blocking or redirecting immune cells.
J&J, GV and Northpond Ventures, though, are backing a company with a different approach, seeding UK-based Mestag Therapeutics with $45 million to explore whether drugging fibroblasts — the cells that create and form the body’s connective tissue — can help get at the underlying mechanisms that let tumors evade the immune systems and keep patients with diseases like IBD in a constant state of inflammation.
“There’s lots of activity looking at the immune cells: B cells, T cells, mast cells,” Mestag CEO Susan Hill told Endpoints News. “But actually the surrounding tissues and the role they might be playing are often overlooked.”
Mestag builds off work at Harvard, The Broad Institute, Cold Spring Harbor and elsewhere that used a relatively new technology, single-cell sequencing, to discover different subtypes of fibroblasts in diseased tissue and show how certain ones were implicated in disease. Harvard’s Soumya Raychaudhuri and Oxford’s Chris Buckley, alongside Mark Coles and Michael Brenner at Brigham and Women’s Hospital, found fibroblasts driving inflammation in arthritis. At Cold Spring Harbor, David Tuveson found fibroblasts implicated in pancreatic cancer.
Fibroblasts, they showed, don’t simply form the structure of tissues. They also secrete signals that communicate with other cells and particularly immune cells, directing them on where to go.
Hill said Mestag will try to develop drugs that can effectively reprogram a subset of fibroblasts around a tumor so that the cells go from immune-suppressive to immune-activating. The goal would be to use the drug in combination with checkpoint inhibitors, one of a phalanx of approaches researchers have deployed in an effort to boost immunotherapies or apply them to more patients.
The company will similarly try to change the signals coming from fibroblasts implicated in inflammation. Hill said she believed the company could get at a more underlying mechanism for inflammation than current therapies that try to suppress the immune system.
“Often in many inflammatory indications, the top therapeutic approaches are targeting immune effector cells. But when you look at the clinical data, the majority of patients never really reach proper clinical remission,” Hill said. “So there must be something” continuing to drive disease.
Mestag announced an initial seed in April, with $11 million from J&J and SV Health Investors. They announced a $34 million extension Monday led by Forbion and joined by GV and Northpond alongside the previous two backers.
In addition to providing early investment, J&J also inked a partnership the now 25-person company. The two will use single-cell analysis and other tools to find novel targets for inflammatory diseases.
Those efforts remain early stage, though. Hill said the company is still in discovery and would not be in the clinic for at least a couple of years.