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) – have inadequate or no therapeutic options.

Pipeline

Progressive Multiple Sclerosis

Abata is rapidly advancing its early programs with plans to initiate three clinical studies by 2025.

Our initial pipeline includes our lead program for progressive multiple sclerosis (MS), as well as programs in Type 1 diabetes and inclusion body myositis – all tissue-specific autoimmune diseases with substantial unmet need and a strong rationale for our Treg approach. We will also develop therapies for other tissue-specific inflammatory and autoimmune diseases where we believe Tregs can make a difference.

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 DR2a/b – estimated to be about 45,000 patients in the U.S. today. There are no approved therapies for non-relapsing 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.

Additional Programs

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 the genetic HLA haplotype DR3-DQ2 (over half of patients) who are early in autoimmune pathogenesis, ultimately aiming to prevent the onset of symptomatic disease and insulin dependence.

Inclusion Body Myositis

Inclusion body myositis (IBM) is a debilitating disease characterized by inflammation that leads to muscle damage and weakness. Today, there are no therapies. Because Tregs play a role in muscle regeneration, we believe Treg cell therapies have the potential to address the unique pathogenic process in IBM. Our Treg cell therapy will treat patients with the genetic HLA haplotype DR3, an estimated 75% of patients.