SCIENCE
Our Target: The Soluble Interleukin 7 Receptor (sIL7R)
sIL7R is a novel T cell activator involved in the immunopathogenesis of multiple sclerosis (MS) and various other autoimmune diseases.
Genetically-Driven: sIL7R is upregulated by genetic variants that increase the risk of MS and other autoimmune diseases.
Significant Population: sIL7R is elevated in up to 66% of MS patients and patients of other autoimmune diseases (SS, SLE, RA, T1D).
Validated Pathway: sIL7R enhances T cell activity and autoimmunity in mouse model of MS.
Pathway Selectivity: pathway has shown preferential expansion of auto-reactive T cells.
Multiple Indications: sIL7R is upregulated and correlates with disease activity in numerous autoimmune diseases (MS, SS, SLE, RA, T1D).
Significant Population: sIL7R is elevated in up to 66% of MS patients and patients of other autoimmune diseases.
Pathway Selectivity: pathway has shown preferential expansion of auto-reactive T cells.
Elevated levels of sIL7R drive the expansion, activation, and migration of effector T cells, in particular memory T cells, and promotes self-reactive immune responses that drive autoimmunity and anti-tumor immunity.
Our Approach: ABS Accurately Dials Immunity for Treatment of Autoimmune Diseases and Cancer by Controlling the Levels of sIL7R.
sIL7R is elevated in MS and other autoimmune diseases by MS risk variants that alter splicing of IL7R pre-mRNAs. ABS leverages this splicing mechanism to control the expression of sIL7R for treatment of autoimmune diseases and solid tumors.
ABS reduces the levels of sIL7R to treat autoimmune diseases.
ABS enhances the levels of sIL7R to treat solid tumors.
ABS Approach to Treat Autoimmune Diseases: To correct the levels of sIL7R to restore immune homeostasis instead of causing immunosuppression.
ABS is developing two drug candidates that restore the elevated levels of sIL7R in patients to normal. This approach eliminates the immunopathological effects of sIL7R and restores immune homeostasis while avoiding profound immunosuppression.
ABS-066 is a splicing-modulating antisense oligonucleotide that reduces the expression of sIL7R.
sIL7R is elevated in MS and other autoimmune diseases by MS risk variants that alter splicing of IL7R pre-mRNAs. ABS-066 reduces the expression of sIL7R by correcting this alteration in splicing of IL7R pre-mRNAs.
ABS-2005 is a monoclonal antibody that specifically inhibits sIL7R while sparing the canonical membrane-bound IL7R.
ABS-2005 is the first monoclonal antibody that discriminates between the soluble (sIL7R) and membrane-bound (mIL7R) isoforms of IL7R. By inhibiting sIL7R and not mIL7R, ABS-2005 selectively drives the therapeutic effects of sIL7R inhibition without inducing the immunosuppressive side effects associated with mIL7R inhibition.
ABS Approach to treat solid tumors: Enhance the expression of sIL7R to increase tumor infiltration and anti-tumor activity of T cells.
Given the pro-T cell properties of sIL7R, upregulation of sIL7R is a novel approach to activate anti-tumor immunity. ABS is developing two drug candidates that enhance the expression of sIL7R to increase the expansion, activation, and tumor infiltrating capacity of tumor-specific T cells.
ABS-001 is a splicing-modulating antisense oligonucleotide that enhances the expression of sIL7R.
ABS-001 enhances the expression of sIL7R by increasing the splicing alteration that produces it.