Going after fibroblasts to bust through the ceiling of cancer and inflammatory disease treatments
CEO: Susan Hill, Ph.D.
Scientific co-founders: Michael Brenner, M.D., David Tuveson, M.D., Ph.D., Dr. Chris Buckley, MBBS, Soumya Raychaudhuri, M.D., Ph.D., Mark Coles, Ph.D.
Based: Cambridge, U.K.
Clinical focus: Targeting fibroblasts to treat cancer and inflammatory disease
The scoop: Mestag Therapeutics is pursuing treatments for cancer and inflammatory diseases by going after an oft-overlooked type of connective tissue cell. Fibroblasts have long been studied in the areas of wound healing and fibrosis, or scarring, but were considered bit players when it came to tumors and inflammation.
In recent years, researchers have started to understand that fibroblasts play not just a supporting role but a central one in inflammation. And Mestag’s co-founders realized that not all fibroblasts are created equal—different kinds of fibroblasts play different roles in different diseases. With this understanding, Mestag aims to create new medicines for patients for whom current treatments don’t work or don’t work for long.
What makes Mestag fierce: Targeting fibroblasts isn’t as straightforward as targeting other cells involved in inflammation.
“There’s no obvious answer. It’s not quite as easy as targeting T cells where they are easy to deplete,” said Michael Brenner, M.D., one of Mestag’s founding investigators.
Between the vast literature, the research of its founding team and its computational skills, Mestag is working on new ways to change how fibroblasts are activated and how they expand, Brenner said. It’s also figuring out which types of fibroblasts drive disease and which ones are helpful, or reparative. Some fibroblasts are unique to specific tissues, while others are found across different tissues.
“We’ve got some great ideas about how to target them, which no one has been able to do before,” Brenner added.
One of the major barriers to targeting fibroblasts directly was the old way of thinking. Some players have neglected fibroblasts and focused on how T cells or macrophages get activated, while others have tried to target fibroblasts indirectly.
“People have said, ‘Gee, maybe there is this factor, TGF-beta for example, that’s well studied in the literature and it activates fibroblasts and fibrosis. Maybe we can block that and block fibrosis,'” Brenner said. “That hasn’t worked, by and large.”
Besides a different way of thinking, technological advances have enabled Mestag to pursue fibroblasts.
“Single-cell RNA sequencing… is a really important enabler for some of the work that is now happening,” said Mestag CEO Susan Hill, Ph.D.
Mestag co-founder Soumya Raychaudhuri, M.D., Ph.D. worked closely with Brenner and the other founders to develop single-cell algorithms that allow the company to see subtle differences between fibroblast cell populations, Hill added.
Named for a castle found on the Scottish island of Stroma—also the name of the tissue that surrounds disease—Mestag launched in April with $11 million in seed funding. It extended that round to $45 million in August.
The company hopes its medicines will help patients surmount a threshold in their response to current treatments, Hill said. They could be used alone or in combination with checkpoint inhibitors to make the latter work for more cancer patients, or in combination with rheumatoid arthritis drugs in patients whose disease is not well controlled.
It is working on four discovery-stage antibodies spanning different aspects of fibroblast biology in inflammatory disease and cancer. As it plugs away at its own pipeline, Mestag is also partnering with Johnson & Johnson’s Janssen unit to discover new targets. Janssen has the option to license up to two targets that come out of the collaboration.
Mestag expects to grow to about 60 staffers by the end of the year and advance its lead programs into pre-IND development in 2022. It’s going after cancer and inflammatory disease first, but its work could be useful for a variety of diseases including autoimmune, infectious or neurodegenerative.
“In due course, we may be thinking about other partnerships with other companies because this is a very rich source of biology,” Hill said.
Investors: Forbion, GV, Johnson & Johnson Innovation, Northpond Ventures SV Health Investors.