Steve P. Miller, PhD, has spent much of his career figuring out how to shut off autoimmune responses when he observed dying cells acting as carriers of autoantigens that could modulate the immune system. More than 20 years ago, while a professor at Northwestern University’s Feinberg School of Medicine, Miller discovered that dendritic cells (DCs), a subtype of antigen-presenting cells (APCs), could be changed or turned off to send the right signals to make immunologically tolerant T cells, also known as “tolerogenic.”
Miller’s attention turned toward investigating how best to mimic the apoptotic cells, overriding the expression of dendritic cells. So, Miller partnered with polymer chemist Lonnie D. Shea, PhD, who was at the McCormick School of Engineering, to develop a nanoparticle that interacts effectively with dendritic cells.
In 2013, Miller and Shea helped launch a company spun out of Northwestern University, when Shea was still in Chicago, called Cour Pharmaceutical Development Company, to develop innovative nanobiological therapeutics for acute inflammation, autoimmune, and allergic conditions. After years of experimentation, they developed a formula for nanoparticles of the right size and charge that interact well with the immune system, which is the foundation for their proprietary antigen-specific immune tolerance platform.
Behind what must be some convincing preclinical and clinical data reprogramming the immune system to address the underlying root cause of immune-mediated diseases, the company is hitting its stride more than a decade after its inception.
Today, the company, which now goes by COUR, announced the closing of a Series A investment round, securing approximately $105 million to develop therapies to treat patients with autoimmune and inflammatory diseases. COUR is developing product candidates in myasthenia gravis and type 1 diabetes (T1D) in addition to having partnered products in celiac disease (with Takeda Pharmaceuticals) and primary biliary cholangitis (with Ironwood Pharmaceuticals).
“We think this could be a therapeutic vaccine,” said John Puisis, COUR’s co-founder, CEO, and president. “When we look at our clinical outcomes, people look like they’ve—I don’t want to use the ‘C’ word—but people don’t have the relapse event anymore.”
The investment was co-led by Lumira Ventures and Alpha Wave Ventures, with participation from Roche Venture Fund, Pfizer (as part of the Pfizer Breakthrough Growth Initiative), Bristol Myers Squibb, Angelini Ventures, and the JDRF T1D Fund.
Nanoparticles vs. cell therapies
COUR’s nanoparticles have a functionalized surface that improves uptake and targeted delivery. These nanoparticles contain antigens that are transported to the spleen and liver, where they are released and collected by APCs. These APCs can now initiate immune tolerance by presenting specific antigens as well as harmful co-stimulating factors to the adaptive immune system.
The induction of tolerogenic APCs can quell cellular autoimmune responses by reprogramming autoreactive T cells, causing one of three outcomes: T cell inactivation (anergy), deletion, or conversion to a Treg phenotype. Puisis said that their approach focuses on T cell anergy.
Puisis is confident that COUR has a product superior to competitors using cell therapies, such as those using chimeric antigen receptor (CAR) approaches, like Kyverna’s autologous CAR T cells and Artiva’s allogeneic CAR NK cells, as well as those using regulatory T (Treg) cells, like QuellTx.
Though Puisis didn’t discuss the use of their technology for other indications, reprogramming T cells could be therapeutic in several settings, including cancer. Indeed, there is published research on methods for antigen self-presentation and immunosuppression reversal as a personalized cancer immunotherapy strategy.
COUR’s website does list work being done in the gene therapy space. As many gene therapies can lead to an immune response of neutralizing antibodies to biologics, COUR’s nanoparticle platform could be used to build tolerance to gene therapy treatments potentially.
Interestingly, Puisis said that COUR’s nanoparticles have the potential to reprogram T cells that can pass through the blood-brain barrier and into cerebrospinal fluid. Theoretically, these T cells could regulate the microglia that act as the nervous system’s APCs. Given the extensive research on neuroinflammatory responses triggered by multiple sclerosis and caused by neurodegenerative diseases, this is particularly intriguing. However, Puisis didn’t comment on any work being done with COUR’s technology in the nervous system.
Before hanging a hat on the broad potential of COUR’s tolerogenic nanoparticles, the company still has to navigate ongoing clinical trials. That’s where the funding announcement comes into play, as the funds will be used to support the advancement of COUR’s myasthenia gravis and T1D product candidates into Phase IIa clinical trials. According to Puisis, COUR’s work on celiac disease is in the hands of their partner, Takeda.
As for the CAR field, which has blossomed of late, it must keep its eyes on the tolerogenic nanoparticle space. Or perhaps the two technologies could come together someday. But for now, it is a race to capture as big a slice as possible in the massive autoimmune disease space.