POS1342 depletion of KLRG1+ T CELLS in a first-in-human clinical trial of ABC008 in Inclusion Body Myositis (IBM)

Background Inclusion body myositis (IBM), a relentlessly progressive autoimmune skeletal muscle disease, has no effective available pharmacological therapy. A prominent feature of IBM on microscopy is highly differentiated effector CD8+ cytotoxic T (Tc) cells invading non-necrotic myofibers [1]. These Tc cells, known to be relatively resistant to apoptosis, express markers including killer cell lectin-like receptor G1 (KLRG1) [2]. ABC008, a first-in-class humanized, afucosylated monoclonal antibody (mAb) specific for KLRG1, selectively depletes these highly differentiated Tc cells while sparing other blood cell populations, e.g., naïve, central memory, and regulatory T cells and B cells. ABC008 has been designed to treat diseases mediated by these Tc cells, including IBM and T-cell large granular lymphocytic leukemia (T-LGLL). IBM and rheumatoid arthritis overlap clinically with T-LGLL and share similar expansions of large granular lymphocytes (LGLs), which also express KLRG1. We report here our preliminary data from our ongoing trial of ABC008 in IBM (NCT04659031)..

Biologic and clinical activity of tivozanib (AV-951, KRN-951), a selective inhibitor of VEGF receptor-1, -2, and -3 tyrosine kinases, in a 4-week-on, 2-week-off schedule in patients with advanced solid tumors

Purpose: To assess the maximum tolerated dose (MTD)/dose-limiting toxicities (DLT), safety, pharmacokinetics, and pharmacodynamics of tivozanib, a potent and selective oralVEGF receptor (VEGFR) tyrosine kinase inhibitor. Experimental Design: Dose levels of 1.0, 1.5, and 2.0 mg/d tivozanib for 28 days followed by 14 days of medication were explored in patients with advanced solid tumors. Results: Forty-one patients were enrolled. Animal data incorrectly predi