Abcuro is advancing first-in-class programs in autoimmunity and cancer in which highly cytotoxic immune cells play a critical role.
Our lead product candidate, ABC008, is a monoclonal antibody which binds to highly cytotoxic T cells (KLRG1+ T cells), which are then depleted via antibody-dependent cellular cytotoxicity (ADCC). The ADCC potency of ABC008 has been enhanced by modification of the level of fucosylation in its Fc region. We are currently studying ABC008 in a Phase 1 clinical trial.
Inclusion Body Myositis (IBM)
Inclusion body myositis (IBM) is the most prevalent myopathy in adults older than age fifty, with over 50,000 patients estimated in the United States and Europe. This debilitating disease is characterized by progressive weakness and atrophy of muscles of the arms and the legs, as well as muscles involved in swallowing. IBM is chronically progressive and results in severe disability and premature death.
IBM is an autoimmune condition in which highly cytotoxic T cells attack muscle which leads to degeneration of the tissue. Muscle tissue from patients with IBM shows the presence of highly differentiated, KLRG1+ cytotoxic T cells destroying muscle fibers.
There are currently no available therapeutic options for IBM. Non-specific immunosuppressants or corticosteroids have not demonstrated efficacy in IBM and thus, are not widely used.
T Cell Large Granular Lymphocytic Leukemia (T-LGLL)
T cell large granular lymphocytic leukemia (T-LGLL) is an autoimmune disorder characterized by clonally expanded CD3+CD8+ cytotoxic T lymphocytes attacking neutrophils and red blood cell precursors, leading to neutropenia and anemia. Neutropenia causes frequent infections, which are a major cause of premature death in patients with T-LGLL. Anemia results in transfusion-dependence in approximately one third of patients.
Given the lack of approved therapeutic options for T-LGLL, about 50% of patients utilize off-label therapies such as the non-specific immunosuppressant methotrexate. Limited efficacy of current standard of care is reflected in an overall reduced life expectancy for T-LGLL patients.
Additional Indications
We are actively advancing ABC008 in preclinical studies for the potential treatment of a number of KLRG1+-driven T/NK cell lymphomas in which the malignant expansion of highly cytotoxic KLRG1+ T and NK cells leads to substantial morbidity and mortality.
Additional indication expansion opportunities may also exist for ABC008 across a number of autoimmune disorders that have been found to have a significant presence of highly cytotoxic KLRG1+ T cells.
ABC015 is a monoclonal antibody product candidate designed to interrupt the interaction of KLRG1 with E- and N-cadherin, its cognate ligands found on the surface of cancer cells.
Blocking KLRG1, an inhibitory immune checkpoint receptor, on mature T and NK cells, from binding to its ligands on cancer cells could allow these immune cells to more effectively kill cancer cells.
In comparison to PD-1, KLRG1 has superior attributes such as expression on the most potent highly cytotoxic lymphocytes, including the most differentiated T cells and NK cells.
REFERENCES:
ABC008
- Pereira et al., The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity, MAbs 2018 Jul;10(5):693-711
IBM
- Shelly et al., Epidemiology and Natural History of Inclusion Body Myositis: A 40-Year Population-Based Study, Neurology 2021 May 25;96(21):e2653-e2661
T-LGLL
- Shah et al., A population-based study of large granular lymphocyte leukemia, Blood Cancer J, 2016 Aug 5;6(8):e455
- Dinmohamed et al., Population-based analyses among 184 patients diagnosed with large granular lymphocyte leukemia in the Netherlands between 2001 and 2013, Leukemia, 2016 Jun;30(6):1449-51
