Xolremdi (mavorixafor) / X4 Pharma, Abbisko, Norgine, taiba - LARVOL DELTA

Trial in progress: A pivotal Phase 3 study to investigate efficacy, safety, and tolerability of mavorixafor in participants with primary chronic neutropenia – trial update (ASH 2025) - P3 | "This pivotal study, evaluating the efficacy, safety, and tolerability of mavorixafor in participants with CN experiencing recurrent and/or serious infections, is expected to support the registration of mavorixafor, alone or in combination with G-CSF, for the treatment of primary chronic neutropenia.This trial (NCT06056297), initiated in 2024, has close to 100 study centers activated and continues to enroll participants with 1 of 3 primary CN types (congenital, acquired idiopathic, and acquired autoimmune), including those who have been inadequately controlled (ANC <1000 cells/µL) while on a stable G-CSF regimen from baseline. Multiple sites are recruiting; many are accepting patient referrals."

Clinical • P3 data • Aplastic Anemia • Dermatology • Glomerulonephritis • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lupus Nephritis • Musculoskeletal Pain • Myelodysplastic Syndrome • Nephrology • Neutropenia • Osteoporosis • Rheumatology • Thrombocytopenia • Vasculitis

Role of genetic testing in diagnosing patients with severe congenital neutropenia: Results from PATH4WARD genetic testing program (ASH 2025) - P1/2 | "In 2022, at age 11 years, the male patient was found to harbor CXCR2 c.865C>T,p.Arg289Cys, a variant associated with SCN due to CXCR2 deficiency.1 In 2023 the patient was enrolled ina Phase 1b and Phase 2 clinical trial investigating mavorixafor in participants with congenital neutropeniaand chronic neutropenia disorders, including chronic idiopathic neutropenia (NCT04154488)...Despite this substantial reduction in G-CSF, the patient'sabsolute neutrophil count remained at or above approximately 1000 cells/µL throughout the study. Thiscase highlights the value of genetic testing in establishing a molecular diagnosis and enabling access toinvestigational agents through clinical trial participation, with the potential to improve clinical outcomes."

Clinical • Hematological Disorders • Immunology • Neutropenia • Primary Immunodeficiency • CD40LG • CSF3R • CXCR2 • CXCR4 • ELANE • GATA2 • TCIRG1

EMU-116: An oral CXCR4 antagonist as mobilizer of stem and immune cells in normal, neutropenic and sickle cell mice. (ASH 2025) - "The use of CXCR4 antagonists as cell mobilization agents has resulted in 3 FDA approved drugs for use inhematopoietic stem cell transplantation (Plerixafor, Motixafortide) and for treating neutropenia(Mavorixafor). In Swiss mice, EMU-116 dosed orally providesenhanced responses to cyclophosphamide indicating a potential use in chemotherapy-inducedneutropenia. In sickle cell mice, EMU-116 boosts LSKs when dosed orally and could possibly be utilizedfor a future in vivo gene therapy setting with superior effects to Plerixafor."

Immune cell • Preclinical • Bone Marrow Transplantation • Chemotherapy-Induced Neutropenia • Gene Therapies • Genetic Disorders • Hematological Disorders • Neutropenia • Sickle Cell Disease

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

Mavorixafor for Patients with Chronic Neutropenic Disorders Treated with G-CSF: Preliminary Response Data and G-CSF Dose Reduction in an Ongoing Phase 2, Open-Label, Multicenter Study Support Reduction in G-CSF Dosing (ASH 2023) - P1/2, P3 | "Our report shows that chronic treatment with oral, once-daily mavorixafor in combination with G-CSF resulted in durable increases in ANC compared with BL for ≥3 months in 3 study participants. Reduction of injectable G-CSF dosing was implemented in 2 study participants with CIN following robust ANC increase observed after the first 2 months of combination treatment. These preliminary data also support the safety of concomitant treatment with G-CSF and mavorixafor."

Clinical • P2 data • Dermatology • Hematological Disorders • Infectious Disease • Neutropenia • ELANE

A Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious Infections (clinicaltrials.gov) - P3 | N=176 | Recruiting | Sponsor: X4 Pharmaceuticals | Trial completion date: Aug 2026 ➔ Nov 2027 | Trial primary completion date: Jul 2026 ➔ Sep 2027

Trial completion date • Trial primary completion date • Hematological Disorders • Immunology • Infectious Disease • Neutropenia

Mavorixafor, a Novel CXC4 Agonist for WHIM Syndrome: Challenges in Successful Drug Development in Rare Hematologic Disorders (ASH 2024) - No abstract available

Hematological Disorders

Mavorixafor for Treatment of WHIM Syndrome (ASH 2024) - No abstract available

Rare Diseases

Trials in Progress: A Phase 3 Study to Investigate Efficacy, Safety, and Tolerability of Mavorixafor in Participants with Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders (ASH 2024) - "All efforts will be made to ensure home health visits are conducted to the same standard as in-person study visits. In conclusion, this randomized, double-blind, pivotal study aims to evaluate the efficacy, safety, and tolerability of mavorixafor in participants with CN experiencing recurrent and/or serious infections and will support the registration of mavorixafor for the treatment of congenital, acquired primary autoimmune, or idiopathic as a monotherapy and in combination with G-CSF."

Clinical • P3 data • Anemia • Aplastic Anemia • Dental Disorders • Dermatology • Fatigue • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Periodontitis • Pneumonia • Primary Immunodeficiency • Respiratory Diseases • Septic Shock

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

Efficacy and Safety Study of Mavorixafor in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome (clinicaltrials.gov) - P3 | N=31 | Active, not recruiting | Sponsor: X4 Pharmaceuticals | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Dermatology • Infectious Disease • CXCR4

Drug-Drug Interaction Potential of Mavorixafor (clinicaltrials.gov) - P1 | N=38 | Completed | Sponsor: X4 Pharmaceuticals | Recruiting ➔ Completed

Trial completion

EVALUATING THE SAFETY AND EFFICACY OF MAVORIXAFOR, AN ORAL CXCR4 ANTAGONIST, IN PATIENTS WITH CHRONIC NEUTROPENIC DISORDERS: RESULTS FROM THE PHASE 2 STUDY (EHA 2025) - "Treatment with mavorixafor, alone or with stable dosage or dosage-adjusted G-CSF, was generally well tolerated and meaningfully and durably increased ANC levels in participants with CN regardless of subtype."

Clinical • P2 data • Hematological Disorders • Infectious Disease • Neutropenia • ELANE • SRP54

MAVORIXAFOR, AN ORAL CXCR4 ANTAGONIST, ALLOWS FOR GRANULOCYTE-COLONY STIMULATING FACTOR DOSE DE-ESCALATION IN PATIENTS WITH CHRONIC IDIOPATHIC NEUTROPENIA AND CONGENITAL NEUTROPENIA (EHA 2025) - "The majority of participants and investigators were willing to substantially reduce or discontinue G-CSF use with mavorixafor treatment. All participants with congenial neutropenia concurrently treated with G-CSF, including one with ELANE, were able to decrease G-CSF while maintaining normal mean ANC levels. This study provides the first evidence that a significant subset of patients with CIN may be able to successfully transition off G-CSF to mavorixafor, providing an oral option to treat chronic neutropenia."

Hematological Disorders • Infectious Disease • Neutropenia • ELANE

CXCR4-R334X MOUSE: A MODEL TO INVESTIGATE THE PATHOGENESIS OF WHIM SYNDROME AND ASSESS NOVEL GENE CORRECTION THERAPY (EHA 2025) - "Treatment is conservative with immunoglobulin supplementation, administration of recombinant G-CSF, low-dose Plerixafor/Mavorixafor, HPV vaccination; haematopoietic stem cell transplantation (HSCT) has anecdotally reported to be curative. These preliminary results show that murine HSPC are highly permissive to mRNA delivery by LNPs transfection, ex vivo. Next, we will apply this protocol to HSPC isolated from WHIM mice for gene correction of Cxcr4-R334X mutation by testing ABE-machinery and ultimately prove the efficacy of this approach in the preclinical disease model."

Preclinical • Bone Marrow Transplantation • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Leukopenia • Neutropenia • Primary Immunodeficiency • CXCR4

X4 Pharmaceuticals Presents Positive Phase 2 Chronic Neutropenia Trial Data in Poster Presentations at the 30th Annual Congress of the European Hematology Association (EHA) (GlobeNewswire) - P1b/2 | N=32 | NCT04154488 | Sponsor: X4 Pharmaceuticals | "Results from participants receiving oral, once-daily mavorixafor monotherapy showed that mavorixafor durably increased mean ANC from baseline over the 6-month trial. Further analysis showed that those with severe CN achieved nearly 3-fold increases in mean ANC levels out to six months, reaching levels typically targeted by physicians for patients with severe chronic neutropenia; In addition, a sub-study comparing the mean percentage of functional neutrophils in samples from healthy donors (n=5) to participants from the Phase 2 CN study (n=9) showed that the mean percentage of functional circulating neutrophils in CN participants in this sub-study was comparable to that of healthy donors after six months of mavorixafor dosing; Mavorixafor was generally well tolerated as monotherapy and in combination with injectable G-CSF during the trial."

P2 data • Neutropenia

X4 Pharmaceuticals Granted Fast Track Designation for Mavorixafor for the Treatment of Chronic Neutropenia by U.S. FDA (GlobeNewswire) - "X4 Pharmaceuticals...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to mavorixafor, an oral CXCR4 antagonist, for the treatment of chronic neutropenia (CN). The company is currently conducting a global, pivotal Phase 3 clinical trial (4WARD) evaluating mavorixafor in certain primary CN conditions....'With enrollment ongoing in our Phase 3 4WARD trial of mavorixafor in CN, we continue to expect full enrollment in the third or fourth quarter of this year and potential top-line data in late 2026'."

Enrollment status • Fast track • P3 data: top line • Neutropenia

Synthesis and 64Cu-Radiolabeling Strategies of Small Organic Radioconjugates Based on the AMD070 Scaffold. (PubMed, ChemMedChem) - "These are based mainly on nitrogen-rich scaffolds, such as AMD070, and cyclic polyamines such as cyclam in the AMD3100 skeleton. Herein, we describe the synthesis of two novel CXCR4-directed radiopharmaceuticals, combining the AMD070 scaffold as a targeting unit, and bifunctional te1pa macrocycle as a strong 64Cu chelator. The synthesis of the conjugates and optimization of 64Cu-radiolabeling are presented, opening the way for future in vitro and in vivo studies."

Journal • Oncology • CXCR4

WHIM Syndrome Diagnosis in a Parent and Child (CIS 2025) - "Mavorixafor was started and pegfilgrastim discontinued with no sinopulmonary infections or hospitalizations since initiation. However, skin rashes worsened, and he developed an axillary abscess requiring trimethoprim-sulfamethoxazole and cephalexin therapy...PIDs with milder phenotypes are often not considered in adult patients until severe manifestations occur, as seen in Case 1. Diagnosis of PIDs should prompt early immune evaluation with consideration of genetic testing in family members."

Clinical • Dermatology • Immunology • Infectious Disease • Otorhinolaryngology • Pneumococcal Infections • Pneumonia • Primary Immunodeficiency • Respiratory Diseases • Tetanus • CD4 • CD8 • CXCR4

Clinical Response Among Participants with Warts in the Phase 3 Trial, Mavorixafor, an Oral CXCR4 Antagonist, for Treatment of Patients with WHIM Syndrome (CIS 2025) - P3 | "Plerixafor, an injectable CXCR4 antagonist, has shown improvement in warts in WHIM syndrome; however, the question remains whether CXCR4 antagonism shows a wart benefit in this population. Two-year treatment with chronic oral mavorixafor was associated with marked clinical improvement in wart severity, providing further evidence that CXCR4 antagonism leads to wart improvement in patients with WHIM syndrome."

Clinical • P3 data • Dermatology • Immunology • Infectious Disease • Primary Immunodeficiency

Mavorixafor Inhibits Pathogenic Cxcr4 Signaling and Function in T Lymphocytes from Patients with WHIM Syndrome in vitro (CIS 2025) - P3 | "This study represents the first comprehensive characterization of CXCR4 GOF phenotypes in T lymphocytes from a large cohort of individuals with WHIM syndrome. The correction of underlying molecular defects may be linked to improved leukocyte mobilization observed in participants in the mavorixafor WHIM syndrome phase 3 trial."

Preclinical • Dermatology • Hematological Disorders • Immunology • Infectious Disease • Primary Immunodeficiency • CXCL12

Norgine strengthens rare disease portfolio with acquisition of Theravia (PRNewswire) - "Norgine and Theravia announced today that they have entered into a definitive agreement under which Norgine will acquire Theravia, an international pharmaceutical company specialising in cutting-edge treatments for patients with rare and debilitating conditions....With the acquisition of Theravia, Norgine will now have...core products in its rare disease portfolio (PEDMARQSI, eflornithine, mavorixafor, SIKLOS) thereby comprising a franchise of critical scale with the ability to be a key growth driver in the medium-to-long-term."

M&A • Dermatology • Genetic Disorders • Hematological Disorders • Otorhinolaryngology

Mavorixafor: a CXCR4 antagonist for WHIM syndrome. (PubMed, Immunopharmacol Immunotoxicol) - "Mavorixafor 400mg daily effectively increases WBC count, reduces disease symptoms and infection burden in WHIM syndrome patients ≥12 years. Future clinical programs will continue to evaluate the safety and efficacy of mavorixafor in patients with chronic neutropenic disease."

Journal • Review • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Neutropenia • Primary Immunodeficiency • Thrombocytopenia • CXCL12

Mavorixafor, CXCR4 antagonist, a novel treatment for WHIM syndrome, first FDA approval 2024. (PubMed, Ann Med Surg (Lond)) - "Traditionally, WHIM syndrome has been managed with intravenous immunoglobulin (IVIG) and filgrastim (granulocyte colony-stimulating factor). These findings underscore the potential of Mavorixafor to significantly improve clinical outcomes for patients with WHIM syndrome, offering a more effective and targeted treatment option. The approval of Mavorixafor not only enhances current therapeutic strategies but also paves the way for future research into CXCR4 antagonists, potentially revolutionizing the management of WHIM syndrome and similar immunodeficiencies."

FDA event • Journal • Dermatology • Hematological Disorders • Infectious Disease • Neutropenia

Drug-Drug Interaction Potential of Mavorixafor (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: X4 Pharmaceuticals

New P1 trial