Not just a WHIM - X4P-001-RD shows promise

CAMBRIDGE, Mass.—X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 allosteric antagonist drugs to improve immune cell trafficking to treat cancer and rare disease, announced today the presentation of clinical data demonstrating safety and promising activity of X4P-001-RD in patients with WHIM syndrome. The X4P-001-RD clinical data is from the ongoing open-label Phase 2 portion of a Phase 2/3 study in patients with WHIM syndrome, and the presentation was made at the 23rd Congress of the European Hematology Association (EHA) taking place on June 14-17, 2018 in Stockholm, Sweden.

WHIM syndrome is a primary immunodeficiency disease caused by a mutation in the C-X-C receptor type 4 (CXCR4) gene resulting in susceptibility to certain types of infections. WHIM is an abbreviation for the characteristic clinical symptoms of the syndrome: warts, hypogammaglobulinemia, infections and myelokathexis. Because patients are highly susceptible to infections, WHIM syndrome is associated with significant morbidity beginning in early childhood and continuing throughout life. Current therapy is limited to treatment of acute infections with antibiotics or prevention through the use of intravenous immunoglobulin or G-CSF.

X4P-001-RD, an oral, small molecule inhibitor of CXCR4 is being developed for use as a life-long treatment for patients with WHIM syndrome and other primary genetic immunodeficiencies. Within the bone marrow, a normally functioning CXCR4 receptor controls the release of neutrophils and leukocytes into the blood stream, thereby ensuring normal immune surveillance functions throughout the body. X4P-001-RD is designed to normalize the signaling for the mutant CXCR4 receptor to promote the release of neutrophils and leukocytes, thereby restoring healthy immunity.

The interim results from the Phase 2 portion of the study demonstrated promising activity of X4P-001-RD with dose-dependent increases in absolute neutrophil and lymphocyte counts in patients with WHIM syndrome. Most patients enrolled in the study to date had meaningful increases in the levels of neutrophil and lymphocyte counts with daily oral administration of X4P-001-RD. Measurement of circulating neutrophils and lymphocytes are endpoints in the X4P-001-RD clinical study because in WHIM syndrome patients, leukocytes are retained in the patient’s bone marrow, causing severe chronic panleukopenia, including neutropenia and lymphopenia. This results in inadequate immune surveillance and function for WHIM syndrome patients.

“In this study, X4P-001-RD showed consistent increases in neutrophils and lymphocytes, the primary biomarker for response to therapy. Increases in these biomarkers are an indication of an improvement in the pathophysiology underlying WHIM syndrome. One exciting example of improvement was a reduction in HPV-related warts following X4P-001-RD therapy in one patient,” noted David C. Dale, MD, Professor of Medicine at the University of Washington, Seattle, WA and lead investigator of the study. “These results are very encouraging and represent a milestone in X4P-001-RD’s development as an oral therapy for WHIM syndrome patients.”

X4P-001-RD was observed to be safe and well tolerated for durations up to 400 days and including doses up to 400 mg daily. Based on this safety profile, along with results of dose-dependent neutrophil and lymphocyte activity, the recommended dose of X4P-001-RD in the future Phase 3 study has been determined to be 400 mg once daily. X4 is completing the Phase 2 portion and plans to initiate the Phase 3 portion towards the end of 2018.

The poster presentation at EHA describes results from the first 8 patients with genetically confirmed WHIM syndrome who were enrolled in the Phase 2 portion of the ongoing Phase 2/3 study (as of data cutoff date of March 20, 2018), and includes the following highlights: all patients demonstrated a dose-dependent increase in neutrophils and lymphocytes from screening values; X4P-001-RD drug exposure showed a dose-dependent increase that correlated with increases in absolute neutrophil count; X4P-001-RD was observed to be well tolerated for durations up to 400 days and up to doses including 400 mg daily, with no serious adverse events (AEs) observed; and preliminary evidence of clinical activity in the form of improvement in warts in one patient has been observed.

“Our clinical program with X4P-001-RD in WHIM syndrome has made significant progress, with the establishment of the recommended dose for our future Phase 3 study in WHIM syndrome,” said Sudha Parasuraman, MD, Chief Medical Officer of X4. “We look forward to moving expeditiously toward starting the pivotal Phase 3 study.”