NEWTON, Mass.--(BUSINESS WIRE)-- Abcuro, Inc., a clinical-stage biotechnology company developing therapies for autoimmune diseases and cancer through precise modulation of highly cytotoxic T and NK cells, will present initial results from a Phase 1 open-label trial of ABC008 in inclusion body myositis (IBM) at American College of Rheumatology Convergence 2021. ABC008, a first-in-class monoclonal antibody, binds KLRG1 (killer cell lectin-like receptor G1), a marker for highly cytotoxic T cells. In the first cohort of individuals with IBM, selective and sustained depletion of highly cytotoxic T cells coincided with early signals of functional improvement. The abstract can be viewed here.

IBM is an autoimmune disease in which cytotoxic T cells chronically attack muscle tissue leading to progressive weakness and limb muscle atrophy.¹ Three individuals with IBM in the open-label, first-in-human, dose-escalation study received 0.1 mg/kg ABC008 subcutaneously, which has been well tolerated to date. The single dose resulted in sustained depletion of highly cytotoxic T cells for at least two months, while sparing regulatory T cells (Tregs). Preliminary data also show potential improvement in disease severity of IBM in the first cohort and evidence of a dose response in the second cohort with ABC008 0.5 mg/kg for depletion of highly cytotoxic T cells.

“We are extremely encouraged and excited by these early clinical results from our study,” said Niti Goel, M.D., Chief Medical Officer of Abcuro. “Our ability to deplete the immune cells contributing to the underlying pathogenesis of IBM represents an important potential breakthrough in an area of significant unmet medical need for this autoimmune disease. Importantly, by demonstrating the mechanism of action of ABC008 in IBM, we have the opportunity to treat other diseases mediated by highly cytotoxic T cells, such as T-LGLL (T cell large granular lymphocytic leukemia) and mature T cell malignancies.”

The IBM clinical trial is being led by Professor Merrilee Needham, a recognized leader in the myositis field, head of the Myositis Research Group at The Perron Institute, and Foundation Chair of Neurology at the Fiona Stanley Hospital in Australia.

“IBM is a refractory autoimmune disease with no disease-modifying treatment options,” said Professor Needham. “ABC008 is a potential first-in-class immunotherapy for IBM that has been shown to reduce the number of harmful cells known to attack muscle in this initial group of IBM patients. We believe ABC008 may result in an effective therapy to modify progression of this debilitating disease and offer the potential for reduced toxicity compared to existing, less selective therapeutic approaches for T cell modulation.”

The IBM Phase 1 study is expected to enroll up to 27 patients at multiple sites in Australia and is designed to primarily assess the safety and tolerability of ABC008. Additional details about the trial are available on ClinicalTrials.gov (NCT04659031).

Based on the promising IBM clinical study results, a study evaluating ABC008 for the treatment of T‑LGLL is planned to be initiated in 2022. Evaluation of additional doses of ABC008 in IBM will inform the selection of doses and schedule to use in upcoming studies.

T-LGLL is characterized by a clonal expansion of highly cytotoxic T cells, which may induce cellular damage and subsequent cytopenia by one of several mechanisms leading to anemia, neutropenia, or pancytopenia. Many IBM patients have expansions of aberrant highly cytotoxic T cells and meet standard diagnostic criteria for T-LGLL.² This disease is often initially treated using immunosuppressive agents such as methotrexate with a complete response rate of <30%³, with a high rate of relapse occurring in more than half of individuals who receive methotrexate therapy.⁴

About ABC008

ABC008 is a first-in-class monoclonal antibody selective for KLRG1 capable of selectively depleting highly cytotoxic T cells, while sparing regulatory and central memory T cells. ABC008 has been designed to treat diseases mediated by highly cytotoxic T cells, including the autoimmune muscle disease inclusion body myositis (IBM), T cell large granular lymphocytic leukemia (T-LGLL), and other mature T cell malignancies. The US Food and Drug Administration (FDA) has granted Orphan Drug Designation to ABC008 for the treatment of IBM.

About Inclusion Body Myositis

IBM is the most prevalent acquired myopathy in adults older than age fifty, impacting at least 50,000 patients in the United States and Europe, with an estimated prevalence in the US of ~180 cases per million adults over fifty. The disease becomes apparent during the later stages of adulthood and is characterized by progressive weakness, atrophy of limb muscles, and difficulty swallowing. IBM can progress to cause severe disability and premature death. Muscle tissue from patients with IBM shows the presence of highly cytotoxic T cells that express KLRG1.

About Abcuro

Abcuro is a clinical stage biotechnology company developing first-in-class immunotherapies for autoimmune diseases and cancer through precise modulation of highly cytotoxic T and NK cells. The company’s lead program is ABC008, which is currently in clinical trials for inclusion body myositis (IBM). ABC008 is also advancing into clinical trials for additional disease indications such as T cell large granular lymphocytic leukemia (T-LGLL) and mature T cell malignancies. The company is also developing ABC015 to selectively activate highly cytotoxic T and NK cells to treat cancer. For more information, visit abcuro.com.

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¹ Greenberg, S.A. Inclusion body myositis: clinical features and pathogenesis. Nat Rev Rheumatol. 2019; 15, 257–272 (2019). https://doi.org/10.1038/s41584-019-0186-x

² Greenberg SA, Pinkus JL, Amato AA, Kristensen T, Dorfman DM. Association of inclusion body myositis with T cell large granular lymphocytic leukaemia. Brain. 2016 May;139(Pt 5):1348-60. doi: 10.1093/brain/aww024.

³ Moignet A, Lamy T. Latest advances in the diagnosis and treatment of large granular lymphocytic leukemia. Am Soc Clin Oncol Educ Book. 2018 May 23;38:616-25. doi: 10.1200/EDBK_200689.

⁴ Bareau B, Rey J, Hamidou M, Donadieu J, Morcet J, Reman O, Schleinitz N, Tournilhac O, Roussel M, Fest T, Lamy T. Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases. Haematologica. 2010 Sep;95(9):1534-41. doi: 10.3324/haematol.2009.018481.

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