X4P-001 in WHIM Syndrome
X4 is developing X4P-001 as a first-in-class, oral, allosteric inhibitor of CXCR4 for the treatment of WHIM syndrome. WHIM syndrome is a rare genetic primary immunodeficiency that results from a “gain of function” mutation in the single gene that encodes for the CXCR4 receptor. This genetic mutation causes premature truncations in the CXCR4 protein, causing the receptor to remain in an “on” state longer than normal, resulting in compromised immune cell trafficking and surveillance.
X4 has achieved clinical proof of concept for X4P-001 in WHIM syndrome where, in the completed Phase 2 trial, X4 observed clinically meaningful increases in neutrophil and lymphocyte counts and a favorable safety profile. Additionally, patients experienced improved infection rates, as reported by patients and the trial investigators. Substantial and visible reductions in wart lesions were also reported in a patient with a history of untreatable severe wart lesions. Based on the positive Phase 2 results, X4 plans to initiate the Phase 3 pivotal trial of X4P-001 in WHIM syndrome.
Currently, there are no approved therapies for the treatment of WHIM syndrome. Care is currently limited to the treatment of the different symptoms of WHIM syndrome. The care of WHIM patients is mainly focused on the prevention and management of infections. None of these treatments, however, have been clinically proven to be effective for treating WHIM syndrome nor do they address the underlying cause of this multi-faceted disease, the genetic defect of the CXCR4 receptor.