Historically, treatments for autoimmune diseases such as type 1 diabetes, myasthenia gravis, and primary biliary cholangitis have relied upon immune suppression. That approach can be effective, but suppressing a sizeable part of the immune system can leave patients vulnerable to infections and side effects such as weight gain and fatigue.
Traditional antigen-specific immune tolerance (ASIT) strategies are not fully specific and do not address the root cause of the disease. Instead, they train the immune system to recognize antigens that have become pathogenic as “self,” essentially resetting the immune system and stopping disease progression. In contrast, COUR Pharmaceuticals is developing a different and highly specific immunological approach that treats the underlying cause of disease.
COUR’s tolerogenic therapeutic approach reprograms the immune system, using nanoparticles that travel to the spleen and liver where they bind to and reprogram monocytes (Figure 1). The body routinely reinforces tolerance to “self” antigens through the processing of apoptotic bodies from dying cells, which is performed through a clearing process by antigen-presenting cells (APCs). These APCs present these nanoparticle-encapsulated antigens as “self” to the T cells, which then launch a T regulatory response at the disease site, down-regulating the immune response.
Dannielle Appelhans, president and CEO of COUR Pharmaceuticals, tells GEN, “This advanced modality lacks many of the challenges that cell and gene therapy face.” It also could be a game-changer for patients.
When the technology was initially out-licensed from Northwestern University it worked with coupled cells, which had some challenges with manufacturing regarding reproducibility and robustness, she says. They were addressed by including a biodegradable polymer that encapsulated the antigen or antigens. Appelhans says that made the process scalable and “really predictable, in that we know how much protein we’re putting in.”
As the tolerogenic technology developed, the business plan was fine-tuned to focus on what the company perceives as the best way to ultimately help patients and the best way to grow COUR into a freestanding biotech company with a platform technology.
“It’s really a targeted approach,” Appelhans emphasizes. “It only affects the antigens that are pathogenic or that are driving disease. Only a little protein is needed. That’s only one to two percent of the overall drug product that we administer. The rest is polymer.”
Programs in the clinic
“We have three proprietary programs in the clinic,” Appelhans says. “This is really exciting and, from a platform technology perspective, it’s great to have clinical data from different programs.”
“We recently shared the results of our first-in-human study in primary biliary cholangitis (PBC) last November at The Liver Meeting™—the annual conference of the American Association for the Study of Liver Diseases. We saw statistically significant improvement in liver stiffness at day 120—just four months into the trial,” she says.
“Furthermore, for myasthenia gravis (MG), we started human dose escalation (in 2024),” Appelhans continues.
Additionally, “Takeda has fully licensed our celiac program and is enrolling patients in a Phase IIb trial.” One of the benefits of targeting celiac disease is that investigators can “use a gluten challenge and see straight away whether it’s having the desired effects on patients.”
A Phase Ib/IIa trial targeting type 1 diabetes is on track to begin administration in diabetic subjects, mid-year, she adds.
Trial data to date suggests the treatments are well-tolerated, with no related severe adverse events. Treatment durability, however, is not yet established. Consequently, COUR is evaluating the possibility of boosters during the first year, but, Appelhans says, “no more often than quarterly.”
Under the radar
This tolerogenic approach “…was a serendipitous discovery that came out of Stephen Miller’s [PhD, professor emeritus] lab at Northwestern University. He’s been working on immune tolerance for about 40 years,” Appelhans says. Miller is now one of COUR’s scientific advisors.
COUR licensed the technology about a decade ago and, since then, has flown under the radar. Appelhans says that’s partially because of, “an atypical history of fundraising.” Despite having three programs in the clinic, “We just completed our Series A round in 2024.” Until then, the company operated off non-dilutive funding from partners such as Takeda.
Its low profile also may be related to its location. The company isn’t in either of the major coastal biotech centers. “The biotech market in Chicago is growing, but it’s not where people first think of (for this industry),” she says.
In-house manufacturing
Initially, like most young companies, COUR outsourced its manufacturing. “Recently, we’ve internalized the drug substance manufacturing,” Appelhans says.
The reason came down to limited contract development manufacturing organization (CDMO) capabilities. “For our type 1 diabetes program, there weren’t any CDMOs that were confident they could produce the four different recombinant proteins we wanted.” Subsequently, “We’ve developed a protein production system using cell-free technology.”
That’s impressive on its own, but this also adds depth to COUR’s capabilities. “With these four recombinant proteins, we cover over 70 epitopes that can drive type 1 diabetes disease…which helps address epitope spreading,” Appelhans says. “Having this wide coverage allows us to not need to know the single antigen that’s driving a disease.” As a result, she expects COUR to be able to produce drug substances in-house for future programs and additional indications.
Selecting exactly which indications to pursue is a key challenge, she admits. “There are about 150 autoimmune diseases and, with our platform, we feel confident we can address any antigen-specific autoimmune disease that’s T cell-mediated or T cell-dependent.” Consequently, with a broadly applicable platform, the company has the option of targeting a wide range of conditions or consolidating treatment around particular organ systems.
“When there’s such potential to help additional patient populations, it’s hard not to want to think about what’s next and to at least get work started in those areas,” Appelhans says.
Deciding what to pursue comes down to identifying the areas of greatest need and balancing them against the company’s capability and capacity to address those needs, as well as the presence of clear animal models, known endpoints, available patients to recruit into trials, and a realistic clinical development plan.
Looking forward
Currently, the programs for type 1 diabetes, PBC, and MG are top of mind for COUR’s scientists, but Appelhans recently announced a new program with
Genentech for an additional indication. She can’t discuss the indication or details, but says, “That will be a big project for us in 2025 and beyond. It’s very exciting.”
“We really view ourselves as a completely different category (of ASIT),” compared to what’s available today, Appelhans emphasizes. As rationale, she points out the potential of their tolerogenic approach to stop disease progression, and possibly even to reverse it.
