BMS obviously feels the potential payoff justifies the risks and the steep price for Padlock. “Other companies have tried, but none were able to get the kind of [chemical] traction that we were able to get,” says Padlock co-founder Paul Thompson, a biochemist at the University of Massachusetts in Worcester. Thompson, then at the Scripps Research Institute, cofounded Padlock in late 2013 with Kerri Mowen, a Scripps molecular immunologist who recently died at a tragically young age of a brain aneurysm, and Michael Gilman, CEO of Padlock and venture partner at Atlas. The company set up with seed funds from Atlas Venture followed by a $23-million series A financing, which included Atlas, Johnson & Johnson Innovation–JJDC (the venture arm of Johnson & Johnson), MS Ventures and Index Ventures (now Medici Ventures). Other biotechs in this space are 4SC Discovery in Planegg-Martinsried, Germany, with a PAD inhibitor program in the discovery stage, and ModiQuest in Oss, Netherlands, which is developing a monoclonal antibody against a PAD-modified substrate.
PADs are a novel target in autoimmunity. The enzymes catalyze citrullination, the conversion of the amino acid arginine to citrulline. As a post-translational modification, citrullination removes a positive charge from the protein surface, a small change that can have major consequences by altering hydrogen bonding, and by modifying the protein's structure and even function. In people with certain genetic backgrounds citrullinated proteins can be immunogenic.
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