X4P-002 / X4 Pharma - LARVOL DELTA

CXCR4 antagonism reduces pneumonia severity in a pharmacological mouse model of CXCR2 loss-of-function-mediated neutropenia. (ASH 2025) - "Mavorixafor, an oralCXCR4 antagonist, has demonstrated a clinical benefit that includes increased neutrophil count andconcomitant reductions in infections for WHIM patients5...The current study aims to address these criticalquestions.MethodsFemale BALB/c mice (10-15 per group) were administered the CXCR2 antagonist navarixin (3 mg/kg) viaoral gavage, followed by daily doses of the CXCR4 antagonist X4P-002 (10 mg/kg) or a vehicle control for 4or up to 14 days, administered two hours after the navarixin dose...Notably, CXCR4 antagonism reduces the severity of pneumonia,likely associated with the normalization of neutrophil counts in infected tissues. In conjunction with ourprevious findings6, which showed that CXCR4 antagonism corrected blood and BM neutrophilabnormalities as well as reduced BM myelokathexis frequency, our data provide strong support forCXCR4 antagonist therapy as a promising treatment strategy for patients with CXCR2 LOF."

Preclinical • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Pneumococcal Infections • Pneumonia • Primary Immunodeficiency • Respiratory Diseases • CXCR2

CXCR4 Antagonism Corrects Peripheral Neutropenia and Mature Neutrophil Accumulation in Bone Marrow in a Pharmacological Mouse Model of CXCR2 Loss-of-Function (ASH 2024) - "Additional clinical manifestations in patients with WHIM syndrome may include warts, hypogammaglobulinemia and lymphocytopenia.1,2 Interestingly, patients with loss-of-function (LoF) variants in CXCR2 display phenotypic features similar to those observed in patients with WHIM syndrome, such as neutropenia, increased infection susceptibility, and myelokathexis.3,4 Mavorixafor, an orally bioavailable CXCR4 antagonist, has demonstrated clinically meaningful increases in absolute neutrophil and lymphocyte counts and concomitant reductions in infections in patients aged 12 years and older with WHIM syndrome, leading to its recent approval by the U.S. Food and Drug Administration.5 Whether CXCR4 antagonist therapy can similarly correct the common pathogenic phenotypes observed in patients with CXCR2 LoF variants as are seen in patients with WHIM syndrome has yet to be determined...Methods Female BALB/c mice (6 mice per group) were dosed with the CXCR2 antagonist navarixin (3..."

Preclinical • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Primary Immunodeficiency • CXCR2

X4 Pharmaceuticals Announces Strategic Prioritization of Programs and Resources Extending Cash Runway Through Expected Key Clinical and Regulatory Milestones (GlobeNewswire) - "Progressing oncology efforts only via potential partnership(s) for the company’s clinical and pre-clinical programs: Waldenström’s macroglobulinemia (WM): Additional Phase 1b clinical data anticipated in early August 2022 in patients with WM caused by both MYD88 and CXCR4 mutations; recently disclosed preclinical data highlight broad potential for treatment of leukemias and lymphomas in wild-type CXCR4; X4P-002: IND-enabling toxicology studies are being finalized for the pre-clinical candidate, a novel, small-molecule CXCR4 antagonist that has demonstrated potential across a number of leukemias and lymphomas and that has been shown to cross the blood-brain barrier; IND filing will now be subject to completing a strategic partnership."

P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia