We have developed a pipeline of small molecule, oral antagonists of the chemokine receptor CXCR4. We believe that inhibition of the CXCR4 receptor creates the potential to provide therapeutic benefit across a wide variety of diseases, including chronic neutropenic disorders and certain types of cancer. While internally we are solely focused on developing our lead candidate, mavorixafor, for chronic neutropenia indications, we are also pursuing partnership opportunities to further advance our oncology programs.
Our lead product candidate is mavorixafor, a first-in-class, oral, selective small molecule CXCR4 antagonist that inhibits receptor binding by CXCL12, its cognate ligand. Mavorixafor is designed to correct the abnormal signaling caused by the dysfunction of the receptor/ligand interaction and enable mobilization of immune cells, increasing levels of circulating white blood cells, including neutrophils, to improve immune system function.
To date, more than 200 individuals in clinical trials have been dosed with mavorixafor, which has demonstrated a favorable tolerability profile across multiple clinical trials.
- In November 2022, we reported positive top-line results from a global, Phase 3 clinical trial (4WHIM) evaluating the safety and efficacy of mavorixafor in people with WHIM syndrome, a rare, inherited, primary immunodeficiency disease typically caused by genetic mutations in the CXCR4 receptor gene. The 4WHIM trial met its primary endpoint and a key secondary endpoint, and we continue to anticipate submitting a U.S. New Drug Application for mavorixafor in WHIM early in the second half of 2023.
- We are also assessing mavorixafor in people with chronic neutropenic disorders, including idiopathic, cyclic, and congenital neutropenia. Following positive results from a Phase 1b clinical trial, we are initiating a Phase 2 trial and expecting additional data announcements and clarity on the potential regulatory path forward for mavorixafor in the treatment of chronic neutropenia in the first half of 2023.
- We have also evaluated mavorixafor in combination with ibrutinib for the treatment of Waldenström’s macroglobulinemia, a rare type of B-cell lymphoma caused by mutations to the MYD88 and CXCR4 genes. We reported positive results from a Phase 1b clinical trial in August 2022 and are seeking partnership(s) to further advance this program.
Mavorixafor has received multiple special designations from global regulatory authorities: in WHIM syndrome, mavorixafor has been granted Breakthrough Therapy Designation, Fast Track Designation, and Rare Pediatric Designation in the U.S., and Orphan Drug Status in both the U.S. and European Union; mavorixafor has also been granted Orphan Drug Status in the U.S. in Waldenström’s macroglobulinemia, regardless of CXCR4 mutation status. In addition, X4 is eligible to receive a Priority Review Voucher (PRV) as a result of mavorixafor’s Rare Pediatric Designation in the U.S.