Rozanolixizumab

Inflammation is like a fire you just can’t put out—inflammatory disorders are chronic conditions after all. If your house is ablaze and you know a gas leak is the cause, dousing the entire home isn’t a targeted way to stop what’s feeding the flames, says John Puisis, co-founder and CEO of Cour Pharmaceuticals. He compares his startup’s drugs to stopping fire at the source. “We go into the basement, and we turn off the fuel valve completely,” Puisis said. Cour’s technology found early validation in the hands of a large pharmaceutical company that picked up one of the biotech’s programs and is currently testing it in mid-stage clinical trials. Now the Chicago-based startup wants to do the same with its internal pipeline and it has raised $105 million for its plans. In doing so, Cour aims to show how its approach to inflammation stands apart from the company’s immunology peers. One of the hottest areas of autoimmune disease research involves harnessing regulatory T cells, or Tregs. These cells in our bodies counteract excessive immune responses. A slew of Treg startups—Sonoma Biotherapeutics, Gentibio, Abata Therapeutics, Quell Therapeutics, and Tr1X—are engineering Tregs to treat a variety of inflammation-driven conditions. The jury is still out on these experimental cell therapies, which have limited, if any, clinical data so far. But Puisis, whose experience includes serving as CEO of autoimmune disorder drug developer Tolera Therapeutics, said one problem with Tregs is that immune suppression from these engineered cells can spread beyond their targets, leading to unwanted effects. “What’s interesting with us versus the others—I won’t name them—they’re doing generalized Tregs, you can actually get off-target spreading,” Puisis said. “We’re basically telling the body ‘don’t attack these cells anymore.’” Cour does not engineer cell therapies. The company works with nanoparticles that trick the body into thinking that they’re cells. Inside of these particles is an antigen for a particular autoimmune disease. The composition of all Cour drug candidates is the same, with the exception of the disease-causing antigen encapsulated within. Cour’s nanoparticles are about the same size as a cell, which is important as they circulate throughout the body. Too large, and they could cause clotting problems, Puisis said. Too small, and the immune system won’t recognize them. Recognition is key to how Cour’s therapies reprogram the immune system, Puisis said. Immune cells that provide surveillance for the immune system pick up the nanoparticles and take them to the spleen, which makes white blood cells, and the liver, which plays a role in the adaptive immune response. Released in these organs without any accompanying inflammatory signals, the immune system perceives the antigens as belonging to the body. The body then produces Tregs that migrate to the site of disease to tamp down immune responses to that antigen. Cour’s technology is based on decades of research by Stephen Miller, a professor of microbiology-immunology at Northwestern University. The startup’s initial focus was celiac disease, an immune response to gluten in certain foods. Preclinical research presented and published in 2015 described how nanoparticles can be generated from biocompatible compounds and used to deliver an antigen to restore immune tolerance. Soon after, Takeda Pharmaceutical began a partnership on the Cour celiac disease therapy. Takeda licensed this therapy in 2019 and is now responsible for its clinical development. Meanwhile, Ironwood Pharmaceuticals holds an option to license a different Cour therapy for primary biliary cholangitis, a rare autoimmune disease affecting the bile ducts of the liver. Puisis isn’t ruling out more pharma alliances, but for now, he said Cour is focusing on developing its own pipeline. Cour’s nanoparticles can encapsulate multiple antigens to address diseases driven by more than one antigen, such as type 1 diabetes. That disease and the rare muscle disorder myasthenia gravis are Cour’s lead indications. Cour selected these diseases because the few available therapies for them leave patients wanting for something better, Puisis said. Drug hunters have pursued antibody therapies for both diseases. The 2022 approval of Provention Bio’s antibody Tzield made that therapy the first FDA-approved treatment for delaying type 1 diabetes progression. Sanofi acquired Provention for $2.9 billion last year. In myasthenia gravis, Argenx markets two antibody fragments, Vyvgart and Hytrulo. Last year, UCB won FDA approval for two myasthenia gravis therapies, Rystiggo and Zilbrysq. While Rystiggo is an antibody that works similarly to Argenx’s drugs, Zilbrysq is a peptide that addresses a different target. The approved type 1 diabetes and myasthenia gravis therapies are chronic treatments, like regular applications of fire suppression that do not extinguish the fire for good. In addition to potentially better efficacy, Cour aims to offer patients long-lasting effects. Puisis said preclinical research suggests the effect of Cour’s therapies last for the lifetime of the animal. To be fair, developers of engineered Tregs also say their therapies may offer long-lasting effects. The durability of both types of treatments still must be shown in human testing. But one advantage that Cour could have over Tregs is manufacturability. Making a therapy from nanoparticles is less expensive and more easily scalable compared to engineering a patient’s cells or donor cells into cell therapies. Cour’s Series A financing was co-led by Lumira Ventures and Alpha Wave Ventures. Other investors include Roche Venture Fund; Pfizer, through its Pfizer Breakthrough Growth Initiative; Bristol Myers Squibb; Angelini Ventures; and the JDRF T1D Fund. Puisis said the financing will support the advancement of both of its programs through Phase 2a clinical development. As for Cour’s name, Puisis said it’s derivative of the word “courage” and is the brainchild of one of the startup’s scientists. “You need a lot of courage to be in biotech and to be in the discovery business,” Puisis explained. Photo by Flickr user Peter Hill via a Creative Commons license