Targeting a genetic cause of poor treatment response in autoimmune disease
Many people with autoimmune disease do not respond adequately to standard treatment.
Autoimmunity BioSolutions is developing ABS-2103, an antibody that selectively targets soluble IL-7 receptor (sIL7R). This immune protein is genetically elevated in about half of patients and is linked to poor treatment response. Our biomarker assays identify the patients most likely to benefit, starting with rheumatoid arthritis.
Our goal is to help these patients respond to the treatments they already receive.
The problem
30 to 50+ percent of patients have an incomplete or inadequate response to standard of care therapies. Many switch treatments, and some progress to more severe disease.
A genetic cause
A common variant in the IL7R gene raises sIL7R levels. About half of people carry the high-sIL7R form (CC genotype), which makes about three times more sIL7R on average, and they tend to respond less well to treatment.
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Our approach
ABS-2103 is designed to lower excess sIL7R concurrent with standard treatment, while sparing the receptor the immune system needs to protect against infections and cancer. Genetic and protein biomarker assays identify who carries the excess.
Helping standard treatment work
When first-line treatment such as methotrexate falls short, many patients move on to a biologic such as adalimumab or infliximab, and many still do not reach a good response. Much of today’s innovation targets patients after first-line treatment fails.
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ABS wants second-line treatment to have a better chance of succeeding across all patients: by lowering genetically elevated sIL7R, ABS-2103 is designed to help these patients respond to the standard of care they receive, before persistent disease activity leads to more severe disease.
What we have done
Defined the genetic mechanism
ABS founders showed how a common IL7R variant changes the way the gene is spliced, increasing production of sIL7R. The work was published in Nature Genetics (2007), in RNA (2013, 2021, 2022), and in Cell (2017).
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Shown that sIL7R makes disease worse
In mouse models of rheumatoid arthritis and multiple sclerosis, adding sIL7R made disease more severe. That points to sIL7R as a cause of worse disease, not just a marker of it.
Validated biomarker assays
A genetic test identifies the variant and a protein test measures sIL7R levels. Both have been validated in a CLIA-certified lab, and together they help define who may benefit.
Linked genotype to treatment response in rheumatoid arthritis
In the BRASS study at Brigham and Women’s Hospital, part of Mass General Brigham, we found that patients without the CC genotype were 5.6 times more likely to reach a good response after a therapy switch.
Shown that ABS-2103 can block that effect
In a mouse model of multiple sclerosis (EAE) that is the most robust and predictive animal model of autoimmune disease, ABS-2103 mitigated the disease worsening and loss of motor function caused by excess sIL7R.
ABS-2103
ABS-2103 is a monoclonal antibody in preclinical development that binds only the soluble form of the IL-7 receptor (sIL7R). We plan to study it with standard treatment in rheumatoid arthritis, in patients selected by CC genotype and elevated sIL7R level.
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The goal is to bring their response closer to that of patients with naturally low sIL7R.
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