Michael Gilman has been in this position before. About 10 years ago, he left an executive research position at Biogen Idec, hooked up with Atlas Venture, and formed a startup called Stromedix—one that got funded, developed a drug, and incidentally was later sold to the big biotech, bringing Gilman back into the Biogen fold.
Now Gilman is at it again. Last summer, over a year after the Stromedix deal closed, Gilman left Biogen again, and reunited with Atlas as an entrepreneur-in-residence. And now his new five-employee startup, Padlock Therapeutics, has secured a big venture round to get going.
“I’m basically a small company guy,” Gilman says. “It’s just what I love to do, I’m good at it, and I want to do it again.”
Cambridge, MA-based Padlock today is announcing it’s raised a $23 million Series A round led by Atlas. Johnson & Johnson Innovation, MS Ventures (the VC arm of Merck KGaA), and Index Ventures are in on the financing as well. The cash will fuel Padlock’s efforts to zero in on what are known as protein-arginine deiminases, or “PAD” enzymes—think of them as rocket fuel for the immune system—and exploit them to make new drugs for autoimmune diseases. Rheumatoid arthritis, lupus, and multiple sclerosis are potential applications for these drugs, though Gilman says Padlock hasn’t decided which way it’ll go first.
Those are big, competitive fields of course. There are several biologic drugs for rheumatoid arthritis—like adalimumab (Humira)—that bring in billions of dollars. But Gilman says that Padlock is trying to combat autoimmune diseases in a fundamentally different way.
Autoimmune diseases occur when the immune system misfires and attacks some part of one’s own body. Almost every drug for an autoimmune disorder counteracts this process by tamping down something in the immune system. Adalimumab, for instance, binds to tumor necrosis factor, a molecule involved in the immune response that characterizes rheumatoid arthritis and a bunch of other autoimmune diseases. But by suppressing the activity of the immune system, such drugs make patients more vulnerable to infections and other complications. The concept that led to the formation of Padlock is, rather than targeting the immune system itself, what if a drug could instead block the antigens, or the molecular beacons that the immune system is being drawn to?
“If you could get rid of the antigens instead, then you have obviously a completely different profile for a drug,” Gilman says.
Presumably, that would mean a drug that wouldn’t leave the body vulnerable to nasty infections and complications. Padlock is attempting to do this by building on work coming out of the Scripps Research Institute from Paul Thompson and Kerri Mowen into PAD enzymes. These enzymes are thought to be implicated in certain autoimmune diseases by transforming normal proteins into slightly modified forms that behave as antigens, spurring the immune system to attack otherwise healthy tissue.
“If you could treat those patients with a PAD inhibitor, and essentially extinguish the supply of fuel to the immune system, you ought to be able to cool the whole thing down,” Gilman says (“Padlock” is a reference to the strategy of locking up the PAD enzymes).
So what makes this a big deal if it works? Take rheumatoid arthritis, for instance. This is where Padlock feels the science, at least so far, is the strongest. Gilman notes that patients with the ailment produce certain unusual antibodies that aren’t seen in healthy people. Many of those antibodies target the antigens produced by PAD enzymes—and they can show up years before the problem has escalated to the point that a person is actually diagnosed with disease. In theory, then, a PAD inhibitor might not just treat rheumatoid arthritis when the disease is established, but
