Schematic overview of mavorixafor in WHIM syndrome. (A) Gain of function mutations in the CXCR4 receptor. Heterozygous autosomal dominant gain-of-function CXCR4 mutations cause WHIM syndrome. Schematic diagram of the human CXCR4 receptor showing extracellular, transmembrane, and intracellular domains and known mutated C-terminal (COOH) residues reported to cause WHIM syndrome. CXCR4 mutations truncate the C terminus by premature termination (red) or frameshift (gray). A stop mutation and a single amino acid substitution that causes WHIM syndrome are reported in position 343 (red and blue). (B) Chemical structure of mavorixafor (X4P-001). (S)-N¹-((¹H-benzo[d]imidazol-2-yl)methyl)-N¹-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine. (C) Study flowchart. Patient P5 discontinued early because of a psoriasiform rash. Patients P3 and P4 did not continue on the extension phase because of personal preference and trial fatigue. (D) Mean (+ standard error) plasma concentration vs time profile of mavorixafor by dose presented on a semilog scale. The horizontal dotted line represents the IC₅₀ of mavorixafor for CXCR4 inhibition, corrected for total (bound and unbound) drug levels.