Opportunity in
Autoimmune Disease
People living with these debilitating diseases need groundbreaking new therapies that are tissue-specific and long-lasting and promote repair.
Despite the development of innovative therapies for some severe autoimmune diseases, the majority of patients – including those with progressive multiple sclerosis (MS) and type 1 diabetes (T1D) – have inadequate or no disease-modifying therapeutic options.
Progressive MS
Progressive Multiple Sclerosis
MS is an autoimmune disease of the central nervous system (CNS).
Myelin, a critical component of a functioning CNS, wraps and insulates nerve fibers to protect them and enable proper transmission of electrical signals. In the CNS of MS patients, myelin is damaged by the body’s own immune cells, thereby exposing nerve fibers. This myelin damage disrupts neural circuits in the brain, hampers communication between the brain and the rest of the body, and makes nerves vulnerable to cell death and neurodegeneration, with long-lasting, often irreversible impact. Progressive MS is characterized by increasing clinical disability independent of acute relapsing pathology.
Our lead program targets MS patients with non-relapsing progressive disease, imaging evidence of ongoing inflammatory tissue injury and an HLA genotype of DRB1*15:01 – estimated to be about 45,000 patients in the U.S. today. There are no approved therapies for non-relapsing secondary progressive MS.
Success in this program supports expansion in two ways: additional HLA haplotypes and ultimately all progressive MS patients, including those who still experience relapses.
Our Treg cell therapy will be armed with a TCR that selectively recognizes degraded myelin. The figure below illustrates progressive MS pathology and how our TCR-Tregs will work.
HEALTHY BRAIN TISSUE
T cells transiently scan the surfaces of APCs but don’t recognize their specific antigen and move on. As a result, no immune response is initiated.
PROGRESSIVE MS: CHRONIC LESION
Inflammatory T cells in a stable, long-lasting aggregate release inflammatory mediators (dotted arrows) that activate macrophages. Macrophages at the lesion edge continuously degrade myelin. Existing MS therapies do not directly address this pathology.
TREG CELL THERAPY FOR PROGRESSIVE MS
A TCR enables Treg activation through antigen-dependent APC interaction. Activated Tregs release factors (green arrows) that suppress lymphoid aggregates, block new lymphocytes and inhibit macrophages. Tregs also produce factors that may promote myelin repair.
T1D
Type 1 Diabetes
Modulating T cells has been clinically demonstrated to affect disease progression in patients with Type 1 diabetes (T1D). Our T1D program will treat patients with a genetic HLA haplotype that occurs in over half of patients. We intend to intervene early, while patients still have beta-cell function, preserve that function and in doing so improve outcomes. Our initial target population is new onset patients with residual beta-cell function; ultimately, we aim to treat patients even earlier in autoimmune pathogenesis to prevent the onset of symptomatic disease and insulin dependence.