Celiac disease is a genetic autoimmune disorder that aﬀects approximately 1% of the global population. In celiac disease, ingestion of gluten leads to damage of the villi in the small intestine causing malabsorption of nutrients. This can lead to long-term health conditions such as nutritional and vitamin deﬁciencies often precipitating early onset of osteoporosis or osteopenia. Furthermore, it can lead to more malignant conditions such as Non-Hodgkin lymphoma and small intestinal adenocarcinoma. Failure to comply with a gluten-free diet will typically lead to relapse as the underlying pathology of celiac disease remains unaddressed.
COUR has developed CNP-101 otherwise known as TAK-101, a biodegradable nanoparticle encapsulating gliadin proteins – the major component of dietary gluten. CNP-101 is the ﬁrst investigational agent to induce antigen-speciﬁc immune tolerance in any autoimmune disease. In a Phase 2, double-blind, placebo-controlled clinical trial, patients with celiac disease were treated with CNP-101 and, starting one week later, were fed wheat gluten for 14 days. While patients receiving placebo developed severe immune responses to gliadin and damaging inﬂammation in their small intestine, patients treated CNP-101 showed signiﬁcantly less inﬂammation.
In addition, CNP-101 showed a trend toward protecting the intestines from gluten-related injury when compared to untreated patients. Based on these Phase 2 clinical results, Takeda acquired the license to CNP-101 in October 2019 and will lead further clinical development.
To our knowledge, this is the first clinical trial to demonstrate induction of antigen specific immune tolerance in any autoimmune disease
Ciarán Kelly, Md, Professor of Medicine at Harvard Medical School
CNP-104 Primary Biliary Cholangitis
Biliary Cholangitis is a rare autoimmune disease targeting the liver; it aﬀects 133,000 people in the U.S. PBC is caused by the dysregulated immune response towards proteins of liver bile duct cells which leads to immune-mediated destruction of bile ducts. As a result, bile acids build up progressively in the liver leading to irreversible damage and scarring of the liver tissue ultimately requiring liver transplant. COUR is developing CNP-104, a biodegradable nanoparticle encapsulating PDC-E2. CNP-104 is design to potentially address the underlying dysregulated immune system responsible for disease progression or recovery of the damaged tissue. CNP-104 received Fast Track designation by the FDA in January 2022.
Myasthenia Gravis (MG) is a debilitating autoimmune disease aﬀecting the neuromuscular system. In MG, dysregulation of the immune system results in immune mediated destruction of the neuromuscular cells resulting in weakening of the skeletal system. CNP-106 is an antigen speciﬁc investigational therapeutic designed to potentially prevent immune mediated neuromuscular destruction. In doing so, CNP-106 aims to reprogram the immune system to address the immunological root cause of disease in Myasthenia Gravis.
Type-1 Diabetes (T1D) is an autoimmune condition driven by immune autoreactivity to proteins found in insulin producing islet cells in the pancreas. Immune mediated destruction of pancreatic islet cells results in loss of insulin production leading to high blood glucose levels which can aﬀect normal functioning of multiple organs in the body. CNP-103 has the potential to address the underlying immunological drivers of T1D and return balance to the immune system via antigen-speciﬁc immune reprogramming to stop immune mediated destruction of pancreatic islet cells. COUR believes that the highly speciﬁc mechanism of action of CNP-103 could achieve long term therapeutic eﬃcacy without causing broad immune suppression.
Vitiligo is a chronic skin disorder caused by selective autoimmune destruction of melanocytes which are specialized cells critical for producing the protective skin darkening pigment melanin. The destruction of these cells leads to skin lesions and depigmentation, and in some cases discomfort due to itchy skin. CNP-107 is an antigen speciﬁc investigational therapeutic designed to potentially address the underlying immune dysfunction driving vitiligo disease pathology. COUR believes that CNP-107 may prevent autoimmune mediated skin depigmentation allowing for skin re-pigmentation via the body’s normal regenerative processes.
Immune Thrombocytopenia Purpura (ITP) is a rare autoimmune disease targeting blood cells called platelets which are required for normal blood clotting. This targeting is caused by the dysregulated immune response towards proteins found on the surface of platelets leading to immune-mediated platelet destruction. As a result, ITP patients experience excessive and frequent bleeding and bruising due to extremely low platelet counts in blood. CNP-105 is an investigational therapeutic designed to reprogram the immune system, stopping it from attacking platelets, and allowing platelet levels in blood to be restored to normal levels.
CNP-108 T Cell Immunogenicity in Gene & Protein Therapies
COUR is developing CNP-108, a biodegradable nanoparticle encapsulating AAV protein replacement, which neutralizes antibodies by harnessing the immune system’s learning power to induce the immune system to build a tolerance to gene therapy treatments.
COUR’s lead program in allergy is directed against the growing threat of peanut allergies in adults and children. Peanut allergy aﬀects approximately 3 million Americans. It is characterized by gastrointestinal, respiratory, skin, and systemic manifestations; in extreme cases anaphylaxis occurs and can rapidly become life-threatening. CNP-201 is a biodegradable nanoparticle encapsulating peanut protein. It has the potential to treat patients with peanut allergy by reducing the need for strict peanut avoidance and reducing the potentially fatal health risks associated with peanut allergy. COUR ﬁled an IND for CNP-201 in December 2020.