Padlock Therapeutics

Padlock CEO Michael Gilman

Padlock Therapeutics
Rethinking autoimmune disease

CEO: Michael Gilman
Based: Cambridge, MA
Founded: 2014
Clinical focus: Autoimmune disease
Company website

The scoop: Today, most treatments for autoimmune disease rely on a fairly simple principle: If the body's natural defenses start acting up, weaken its weaponry to smooth things over. The problem, of course, is that the immune system does a whole lot of important things, too, and curtailing its power can put patients at risk. Padlock Therapeutics, founded last year, is working on some new chemicals that intervene at an earlier stage in the immune process, targeting the enzymes responsible for triggering the body's alarms in the first place in hopes of finding new therapies for some common diseases.

What makes Padlock Therapeutics Fierce: Led by biotech veteran Michael Gilman, the company is pressing forward with hopes of upending the conventional wisdom in immunomodulation. As Gilman puts it, "I think that we may have gotten autoimmune disease entirely wrong for all these years."

The long-held theory in rheumatoid arthritis, lupus and other diseases is that a defect in the immune system leads to "friendly fire," Gilman said, in which the body mistakenly goes after healthy tissues it should leave well alone. But what Padlock has come to understand is that the immune system is simply doing its job; the problem is that it's being tipped off to material it was never meant to see.

That's because of a process called protein citrullination, through which otherwise innocent material is transformed into an antigen and thrust into the immune system's crosshairs. And proteins get citrullinated by enzymes called protein-arginine deiminases, or PADs. Padlock's plan is to block the activity of PADs with small-molecule drugs, shutting off the supply of antigens and thus treating autoimmune disease without having to suppress the immune system.

With all that mapped out, Padlock raised $23 million in December from Atlas Venture, Index Ventures, Johnson & Johnson ($JNJ) Development and MS Ventures, the biotech investment arm of Merck KGaA. That money is now paying for the dirty work of early-stage drug development, and Padlock has its "sleeves rolled up and heads down" with hopes of nailing down drug candidates in both RA and lupus in the next year.

In RA, Padlock believes targeting PADs can not only be an effective treatment for current sufferers but also create a first-of-its-kind upstream therapy for patients who have already broken tolerance to certain antigens but haven't yet developed the disease, Gilman said. And in lupus, the company is fleshing out the role neutrophils--white blood cells that drive inflammation--play in the disease, crafting a PAD inhibitor that might block their reproduction and thus treat lupus. Padlock is pressing forward in both diseases in tandem, and the company expects to identify a top clinical prospect in the next 6 to 12 months, Gilman said.

In the long term, Padlock plans to dig in and explore the wide applications of its portfolio, bolstered earlier this year with the acquisition of some PAD-blocking molecules from GlaxoSmithKline ($GSK). The company's current cash will carry it well into next year, Gilman said, after which Padlock will either mount a Series B or strike some sort of partnership to replenish its coffers.

And while the rising tide of biotech valuations has raised all ships over the past few years, Gilman has seen enough lean times to know how to keep a cool head. Moving from Biogen ($BIIB) to tiny Stromedix and back to Biogen again, Gilman has learned the value of prioritization no matter the capital climate. He looks at portfolio creation as a series of concentric circles with a bull's-eye in the middle.

"With Stromedix there was just a bull's-eye. For Padlock we know our circles," Gilman said. "If we're really constrained, no problem: Focus on the lead program and turn it into something beautiful. If we get more money, we go into the next circle," and so on, leveraging past discoveries and inflection points to widen the scope of R&D.

Investors: Atlas Venture, Index Ventures, Johnson & Johnson Development and MS Ventures

For more:
Atlas' Padlock scoops up some GlaxoSmithKline assets in autoimmunity
Padlock banks $23M with a fresh approach to autoimmune disease

-- Damian Garde (email | Twitter)

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