Inflammation is like a fire that cannot be put out. After all, inflammatory diseases are chronic diseases. If your house is on fire and you know a gas leak is the culprit, dousing the entire house with water is not a targeted way to stop what's causing the blaze, says Cool Pharma. John Puisis, co-founder and CEO of Ceuticals, said: He likens his startup drug to stopping a fire at its source.
“We go into the basement and shut off the fuel valve completely,” Puisi said.
Cour's technology was early validated by a major pharmaceutical company that adopted one of the biotech's programs and is currently being tested in mid-stage clinical trials. Now, the Chicago-based startup wants to do the same with its internal pipeline, for which he has raised $105 million. In doing so, Cour aims to demonstrate how its approach to inflammation differs from its immunology competitors.
One of the hottest areas of autoimmune disease research concerns the use of regulatory T cells (Tregs). These cells in our body fight an excessive immune response. A number of Treg startups, including Sonoma Biotherapeutics, Gentibio, Abashi 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, and so far there is limited, if any, clinical data. However, Puisis, who previously served as CEO of Tolera Therapeutics, a company developing treatments for autoimmune diseases, said one of the problems with Tregs is that these genetically engineered cells can cause immunity. He said the suppression could spread beyond the target and have undesirable effects.
“What's interesting compared to other companies, I won't name names, is that they're doing generalized Tregs, which could actually lead to off-target spread,” Puisis said. he said. “We're basically saying to the body, 'Don't attack these cells anymore.'”
Kool does not develop cell therapies. The company is developing nanoparticles that trick the body into thinking they are cells. Inside these particles are antigens from certain autoimmune diseases. The composition of all Cour drug candidates is the same except for the disease-causing antigens encapsulated inside. Cour's nanoparticles are about the same size as cells, which is important for their circulation throughout the body. If it's too large, it can cause clotting problems, Puissis said. If they are too small, the immune system cannot recognize them.
Awareness is key to how cool therapy reprograms the immune system, Puisi said. Immune cells that monitor the immune system pick up the nanoparticles and transport them to the spleen, where they produce white blood cells, and the liver, where they play a role in the adaptive immune response. When released in these organs without inflammatory signals, the immune system recognizes the antigen as belonging to the body. The body then produces Tregs, which travel to the disease site and suppress the immune response to that antigen.
Cour's technology is based on decades of research by Stephen Miller, a professor of microbiology and immunology at Northwestern University. The startup's initial focus was on celiac disease, an immune response to gluten in certain foods. Preclinical studies published and published in 2015 described how to generate nanoparticles from biocompatible compounds and use them to deliver antigens to restore immune tolerance. Shortly thereafter, Takeda Pharmaceutical began a collaboration on a treatment for cool celiac disease. Takeda approved the treatment in 2019 and is currently in charge of clinical development. Meanwhile, Ironwood Pharmaceuticals has an option to approve another cool therapy for primary biliary cholangitis, a rare autoimmune disease that affects the bile ducts of the liver.
Mr. Puisis did not rule out the possibility of further pharmaceutical partnerships, but said that for now Kool is focused on developing its own pipeline. Cour's nanoparticles can encapsulate multiple antigens to address diseases caused by multiple antigens, such as type 1 diabetes. This disease and the rare muscle disease myasthenia gravis are Kuhl's main indications. Kuhl chose these diseases because there are fewer treatments available and patients want better treatments, Puysis said.
Drug hunters have been pursuing antibody treatments for both diseases. With the approval of Provention Bio's antibody Tzield in 2022, the treatment became the first FDA-approved treatment to slow the progression of his type 1 diabetes. Sanofi acquired Provention last year for $2.9 billion. For myasthenia gravis, Argenx markets two of his antibody fragments, Vyvgart and Hytrulo. Last year, UCB won FDA approval for two myasthenia gravis treatments, Rystiggo and Zilbrysq. Rystiggo is an antibody that works similarly to his Argenx drug, but Zilbrysq is a peptide that addresses a different target.
Approved treatments for type 1 diabetes and myasthenia gravis are long-term treatments such as regular firefighting that does not permanently put out the fire. In addition to potentially greater efficacy, Cour aims to provide long-lasting effects for patients. Puisi said preclinical studies suggest that the effects of cool therapy last for the life of the animal. To be fair, the developers of genetically engineered Tregs also say their treatments may have long-lasting effects. The durability of both types of treatments still needs to be demonstrated in human trials. However, one of the advantages that Cour can have over his Tregs is ease of manufacture. Creating therapies from nanoparticles is cheaper and more easily scalable than processing patient cells or donor cells into cell therapies.
Cour’s Series A funding was co-led by Lumira Ventures and Alpha Wave Ventures. Other investors include Roche Venture Fund. Pfizer, through the Pfizer Breakthrough Growth Initiative; Bristol-Myers Squibb; Angelini Ventures; JDRF T1D Fund. Puisis said the funding will support the advancement of both programs through Phase 2a clinical development. Regarding Cour's name, Puisis said it is derived from the word “courage” and was the brainchild of one of the startup's scientists.
“It takes a lot of courage to be in biotechnology and be in the discovery business,” Puisis explained.
Photo by Flickr user Peter Hill (via Creative Commons License)