Leveraging our unparalleled expertise in diseases of the immune system and CXCR4 biology, we aim to bring innovative treatments to patients with chronic neutropenic disorders.
Chronic neutropenic disorders are rare blood conditions where patients of all ages experience low levels of certain white blood cells called neutrophils. Neutrophils play an important role in the body’s defense against infection. Neutropenia can be defined as a primary immunodeficiency when caused by a genetic abnormality, but dysfunction can also be acquired later in life or a result of as yet unknown causes. Depending on the blood levels of circulating neutrophils (known as absolute neutrophil count, or ANC), disease can be categorized as mild (ANC between 1,000 and 1,500 cells per microliter), moderate (ANC between 500 and 1,000 cells per microliter), or severe (ANC less than 500 cells per microliter).
CXCR4, or C-X-C receptor type 4, is the cell receptor for the chemokine ligand, CXCL12. Chemokines are signaling proteins that guide the movement of immune cells within the body by binding to receptors on the surface of target cells. CXCR4 receptor stimulation by CXCL12 has been shown to play a key role in the expansion, maturation, and mobilization of immune cells, including neutrophils and other types of white blood cells, including lymphocytes and monocytes, into the bloodstream. When the CXCR4/CXCL12 pathway is overstimulated, immune cells become trapped in the bone marrow, leading to immunodeficiency. Conversely, blocking hyperactivated signaling through CXCR4 results in normalized trafficking of immune cells into peripheral blood. We believe that therapeutic inhibition of the CXCR4/CXCL12 axis has the potential to improve immune cell mobilization and human health whether caused by CXCR4 mutation or not.
Our deep understanding of the biology of the CXCR4 pathway has enabled us to advance our lead candidate, mavorixafor, a small-molecule, orally available antagonist of CXCR4, into clinical development. In clinical trials to date, mavorixafor has demonstrated the ability to improve the mobilization of neutrophils, lymphocytes, and monocytes into the blood stream in people with moderate to severe chronic neutropenic disorders, including WHIM syndrome, and certain cancers.
We believe that commercializing mavorixafor and providing a new therapeutic option to individuals with life-threatening CNDs has the potential to revolutionize the treatment landscape, which is currently only served by injectable therapies that have been associated with high-burden side effects and increased cancer risk in some patients.
We also believe that the diagnosis and treatment of chronic neutropenic disorders can be improved through greater access to genetic testing. In partnership with Invitae, we have launched the PATH4WARD program, providing no-cost genetic testing and counseling for individuals who may carry genetic mutations known to be associated with chronic neutropenia