On March 25, 2025 X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, reported financial results for the fourth quarter and full year ended December 31, 2024, and highlighted key 2024 and recent events and expected upcoming milestones (Press release, X4 Pharmaceuticals, MAR 25, 2025, View Source [SID1234651397]).
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"As expected, 2024 was a transformative year for the company and our momentum has continued into 2025," said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. "With the U.S. approval and launch of our first product, XOLREMDI (mavorixafor) in WHIM syndrome, we are now a fully integrated company advancing our mission to serve those with rare immunodeficiencies and few treatment options. As we await word from the EU regulatory authority on the potential approval of mavorixafor for WHIM in that region, we’ve continued to expand our potential reach to the global WHIM community through our recently completed commercialization partnerships in the EU, Australia, New Zealand, and the Middle East and North Africa (MENA) territories."
Dr. Ragan continued: "In addition, we continue to make meaningful progress in our efforts to develop mavorixafor for the larger immunodeficiency population with chronic neutropenia (CN). Following positive results from our Phase 2 trial of mavorixafor in certain CN populations, we are currently conducting a global, pivotal Phase 3 trial in CN. With a large number of sites now activated and global screening ongoing, we expect full trial enrollment in the third or fourth quarter of this year and top-line trial data in the second half of 2026."
Dr. Ragan concluded: "Market research and patient testimonials continue to strengthen our belief that there remains significant untapped potential for XOLREMDI for the U.S. and possibly global WHIM patient populations. We are equally confident in mavorixafor’s future potential to address unmet needs in the global CN community."
Key 2024 and Recent Corporate Highlights
Commercializing XOLREMDI (mavorixafor) in WHIM Syndrome, a Rare Primary Immunodeficiency
•FDA Approval and Launch of XOLREMDI: In May 2024, X4 launched XOLREMDI (mavorixafor) following approval by the U.S. Food and Drug Administration (FDA) for its use in patients 12 years of age and older with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) to increase the number of circulating mature neutrophils and lymphocytes. Concurrent with the approval of XOLREMDI, X4 received a priority review voucher (PRV), which it subsequently sold to another drug developer for $105 million.
•U.S. Launch Update: X4 is continuing to execute on its commercialization of XOLREMDI in the U.S., generating $2.6 million in sales from its mid-May launch through December 2024. During the year, the company advanced disease awareness by engaging with physicians and rare disease patient advocacy groups through a combination of in-person and targeted digital education campaigns. The company’s suite of patient services, including its X4Connect and nurse educator programs, continue to provide access and support for patients prescribed XOLREMDI.
•Clinical Data Publications and Presentations: Journal publications and presentations of clinical data results at top medical meetings, including those of the American Society of Hematology (ASH) (Free ASH Whitepaper), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the Clinical Immunology Society (CIS), have provided further visibility on the XOLRMEDI approval.
•Maximizing the Global Opportunity for Mavorixafor in WHIM Syndrome:
MAA Acceptance. In January 2025, X4 announced that its submitted Marketing Authorization Application (MAA) for mavorixafor in the treatment of WHIM syndrome was validated for review by the European Medicines Agency (EMA), meeting an important corporate milestone. Given a typical 12- to 15-month review process, the company believes approval to be possible in the first half of 2026.
EU/ANZ Partnership. Also in January 2025, the company announced that it had entered into an exclusive licensing and supply agreement under which Norgine Pharma UK will commercialize mavorixafor in Europe, Australia, and New Zealand following any regulatory approvals in those territories. X4 received €28.5 million as an upfront payment and is eligible to receive up to €226 million in potential regulatory and commercial milestone payments in addition to tiered, double-digit royalties.
MENA Partnership. In addition, X4 announced in February 2025, that it had entered into an agreement with taiba rare to distribute and commercialize XOLREMDI for the treatment of WHIM syndrome in Saudi Arabia, United Arab Emirates, Qatar, Oman, Kuwait, Bahrain, and Egypt, following any approvals in those countries. Pending regulatory approvals in the region, taiba expects to be able to make XOLREMDI available to WHIM patients through a named-patient (compassionate use) program that allows physicians to prescribe medicines approved in other countries to local patients with no other treatment options.
Advancing Mavorixafor in Chronic Neutropenia (CN)
•Phase 2 Clinical Data De-Risk Ongoing Phase 3 4WARD Clinical Trial. Throughout 2024, X4 presented positive interim and full data sets from its Phase 2 trial that evaluated mavorixafor in the treatment of people with chronic neutropenia (CN), as a monotherapy and in combination with injectable granulocyte colony-stimulating factor (G-CSF), the only therapy approved in the U.S. for severe chronic neutropenia. The six-month, open-label clinical trial enrolled a total of 23 participants and demonstrated that:
◦Once-daily oral mavorixafor was generally well tolerated +/- G-CSF, with no drug-related serious adverse events reported, consistent with previous clinical studies;
◦Mavorixafor treatment durably and meaningfully increased participants’ mean absolute neutrophil counts (ANC) across all study populations; and
◦Physicians were willing and able to reduce the use of G-CSF in participants also treated with mavorixafor, maintaining mean ANC levels in the normal range.
•Ongoing Phase 3 4WARD Trial. In June 2024, the company announced the initiation of its global, pivotal Phase 3 clinical trial (NCT06056297), evaluating oral, once-daily mavorixafor (+/- G-CSF) in people with congenital, acquired primary autoimmune, or idiopathic CN who are experiencing recurrent and/or serious infections. The 52-week 4WARD trial is a randomized, double-blind, placebo-controlled, multicenter study aiming to enroll 150 participants.
•4WARD Trial Updates. X4 announced today that this first-of-its-kind trial is now activated at ~90% of targeted sites worldwide.
Refining the 4WARD Protocol: Based on FDA and EMA guidance, an amendment to the 4WARD protocol has been implemented, focusing enrollment on those with the highest unmet needs and refining a co-primary endpoint. The trial is now only enrolling participants with moderate and severe neutropenia (ANC below 1,000 cells per microliter), an ANC level consistent with the company’s targeted patient population for mavorixafor, if approved. In addition, the ANC component of the primary endpoint will now be uniform across all participants, seeking to demonstrate infection benefit from an ANC increase of at least 500 cells per microliter in study participants on active drug.
Enrollment Update: Given the average screening rates currently observed, the company expects the trial to be fully enrolled in the third or fourth quarter of 2025, and disclosure of top-line data in the second half of 2026.
Strategic Restructuring
In February 2025, X4 announced a strategic restructuring to sharpen focus and maximize the opportunity for mavorixafor in chronic neutropenia. Related activities included reducing overall headcount, discontinuing research efforts, pausing pre-clinical drug candidate programs, and closing the company’s facility in Vienna, Austria, as well as right-sizing its U.S. commercial field team and streamlining other spending. X4 continues to expect that these efforts will decrease spending by $30-35 million annually.
Fourth-Quarter and Full-Year 2024 Financial Results
•Cash position: X4 had $102.8 million in cash, cash equivalents, restricted cash, and marketable securities as of December 31, 2024. Pro-forma for the €28.5 million payment received from Norgine in January 2025 and the expected financial impact of the strategic restructuring announced in February 2025, the company believes it has sufficient funds to support operations into the first half of 2026.
•Revenue and Cost of Revenue: For the fourth quarter and full year ended December 31, 2024, X4 reported net product revenue of $1.4 million and $2.6 million, respectively, and cost of revenue of $0.3 million and $0.8 million, respectively, related to sales of XOLREMDI.
•Research and Development (R&D) Expenses were $21.7 million and $81.6 million for the fourth quarter and full year ended December 31, 2024, respectively, as compared to $15.3 million and $72.0 million for the comparable periods in 2023. R&D expenses included $1.2 million and $4.3 million of certain non-cash expenses for the fourth quarter and full year ended December 31, 2024, respectively.
•Selling, General, and Administrative (SG&A) Expenses were $15.1 million and $61.5 million for the fourth quarter and full year ended December 31, 2024, respectively, as compared to $9.9 million and $35.5 million for the comparable periods in 2023. SG&A expenses included $1.0 million and $3.9 million of certain non-cash expenses for the fourth quarter and full year ended December 31, 2024, respectively.
•Gain on Sale of Non-Financial Asset: For the year ended December 31, 2024, X4 recognized a gain on the sale of a priority review voucher (PRV) to a third party for $105.0 million in cash. The PRV was awarded to X4 by the FDA under its Rare Pediatric Disease program upon the approval of XOLREMDI. Under this program, the FDA awards PRVs to sponsors of rare pediatric disease product applications that meet certain criteria to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases.
•Net Loss: X4 reported a net loss of $39.8 million and $37.5 million for the fourth quarter and full year ended December 31, 2024, respectively, as compared to $19.1 million and $101.2 million for the comparable periods in 2023. Net loss for the year ended December 31, 2024 includes the sale of a PRV for $105.0 million, as noted above. Net loss included $2.2 million and $8.2 million of stock-based compensation expenses for the fourth quarter and full year ended December 31, 2024, respectively.
Conference Call and Webcast
X4 will host a conference call and webcast today at 8:30 am ET to discuss these financial results and business highlights. The conference call can be accessed by dialing 1-800-267-6316 from the United States or 1-203-518-9783 internationally, followed by the conference ID: X4PHARMA. The live webcast will be accessible through the investor relations section of X4 Pharmaceuticals’ website at www.x4pharma.com. Following the completion of the call, a webcast replay will be available on the website.
About WHIM Syndrome
WHIM syndrome is a rare, combined primary immunodeficiency and chronic neutropenic disorder caused by CXCR4 receptor dysfunction that results in impaired mobilization of white blood cells from the bone marrow into peripheral circulation. WHIM syndrome is named for its four classic manifestations: warts, hypogammaglobulinemia, infections, and myelokathexis, although only a minority of patients experience all four manifestations in the acronym. People with WHIM syndrome characteristically have low blood levels of neutrophils (neutropenia) and lymphocytes (lymphopenia), and as a result, experience serious and/or frequent infections.
About XOLREMDI (mavorixafor)
XOLREMDI (mavorixafor) is a selective CXCR4 receptor antagonist approved in the U.S. as a once-daily oral treatment for use in patients 12 years of age and older with WHIM syndrome to increase the number of circulating mature neutrophils and lymphocytes. XOLREMDI is the only treatment specifically approved for patients with WHIM syndrome in the U.S.
About Chronic Neutropenia and Mavorixafor
Chronic neutropenia is a primary, rare blood condition lasting more than three months, persistently or intermittently, and characterized by increased risk of infections and reduced quality of life due to abnormally low levels of neutrophils circulating in the blood. Neutrophils are retained in the bone marrow by the CXCR4/CXCL12 axis, creating a reserve of cells. Downregulation of the CXCR4 receptor by mavorixafor, an orally active CXCR4 antagonist, has been shown to mobilize functional neutrophils from the bone marrow into the peripheral blood across multiple disease states. The level of circulating neutrophils is typically measured by drawing blood to determine the absolute neutrophil count (ANC).
About the 4WARD Clinical Trial
The 4WARD trial is a global, pivotal Phase 3 clinical trial (NCT06056297) evaluating the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without G-CSF) in people with congenital, acquired primary autoimmune, or idiopathic chronic neutropenia who are experiencing recurrent and/or serious infections. The 52-week trial is a randomized, double-blind, placebo-controlled, multicenter study aiming to enroll 150 participants with confirmed trough ANC levels less than 1,000 cells per microliter at baseline screening and histories of two or more serious and/or recurrent infections in the prior year. The primary endpoint of the trial is based on two outcome measures: annualized infection rate and positive ANC response.