X4 Pharmaceuticals Details Mavorixafor Phase 3 Push, Cost Cuts and Chronic Neutropenia Market Plan

X4 Pharmaceuticals (NASDAQ:XFOR) Executive Chair Adam Craig said the company’s near-term focus is centered on advancing mavorixafor in chronic neutropenia, as the company seeks to position itself as a developer of new therapies for rare blood disorders. Speaking at a Guggenheim-hosted fireside chat with Senior Biotech Analyst Michael Schmidt, Craig outlined operational changes made over the past six months, the rationale for prioritizing the Phase 3 program, and how the company is thinking about the addressable market and commercialization approach.

Strategic focus on chronic neutropenia and cost reductions

Craig said the management team has spent the last six months “focusing the team” on completing a successful Phase 3 program for chronic neutropenia and bringing that indication to patients. He added that X4 has reduced costs and headcount, describing the company as now being “focused on completing our phase III trial successfully.”

The company’s lead asset, mavorixafor, is being developed for patients with low neutrophil counts who are “very exposed to getting infections,” Craig said.

Mavorixafor’s positioning versus G-CSF and other CXCR4 agents

Craig contrasted mavorixafor—an oral CXCR4 inhibitor—with current treatment patterns in chronic neutropenia, where G-CSF is widely used but has limitations. He said about 40% of chronic neutropenia patients receive G-CSF therapy, but noted drawbacks including subcutaneous administration, bone pain, and what he described as a risk of long-term transformation to leukemia with long-term use. Craig also said patients often use G-CSF intermittently rather than continuously, based on his market research description and his experience as a pediatric oncologist.

On competitive dynamics, Craig said plerixafor is an IV CXCR4 compound that has shown limited benefit in WHIM syndrome—mavorixafor’s first indication—and is used in an estimated 2% to 3% of the chronic neutropenia market. He said X4 does not see plerixafor as a main competitor, citing route of administration and limited data in chronic neutropenia.

WHIM commercialization deprioritized, but data seen as validating

Mavorixafor is FDA-approved for WHIM syndrome, which Craig described as “ultra-rare.” He said that when the new leadership team took over in August of last year, the company “was spending more than it was bringing in revenue,” prompting X4 to deprioritize active commercialization in WHIM. Craig emphasized that the company will continue to provide the drug to patients who require it and that it remains available, but said it is “not feasible” to spend more commercial dollars than the revenue coming in for that indication.

Even so, Craig said WHIM data has been helpful in informing chronic neutropenia expectations. He described WHIM as a form of severe neutropenia, with patients having absolute neutrophil counts (ANCs) below 500, along with hypogammaglobulinemia and susceptibility to infections. According to Craig, WHIM experience showed that mavorixafor treatment can improve ANC and infections, albeit in a small sample typical of an ultra-rare disease. He said that is “very validating” for the broader chronic neutropenia hypothesis.

Craig also noted the company has continued to add WHIM patients even after it stopped active promotion, though he characterized the numbers as “very, very small.” He suggested physician awareness of mavorixafor could provide some benefit to WHIM uptake, while reiterating that WHIM is not a commercial priority given the cost-revenue equation.

Market sizing and unmet need in symptomatic chronic neutropenia

Craig cited market research conducted with ClearView Partners estimating roughly 15,000 patients with symptomatic, severe or moderate chronic neutropenia, defined as ANCs below 1,000 or below 500. He said X4’s base case assumption is treating about one-third of those patients—around 5,000—initially as monotherapy, with potential for more combination use with G-CSF over time as data and prescriber experience grow.

On unmet need, Craig pointed to patients who require escalating doses of G-CSF over time, including what he referred to as “super doses,” and to patients who avoid G-CSF due to tolerability and long-term concerns. He highlighted infection burden in the company’s Phase 3 population, stating that about 70% of patients entering the clinical trial have three or more infections per year, and that these are infections requiring emergency room visits, possible hospitalization, and antibiotics.

4WARD Phase 3 design, enrollment plans, and upcoming milestones

Craig outlined the design of X4’s Phase 3 4WARD trial in chronic neutropenia:

• Population: All groups of chronic neutropenia
• Size: 176 patients
• Randomization: 1:1 mavorixafor vs placebo
• Background therapy: Patients in each arm can receive G-CSF (“plus or minus G-CSF”)
• Eligibility: Two infections in the past year
• Endpoints: Increase in ANC (primary) and reduction in infections (co-primary)

Craig said the company’s aim is to complete enrollment by the end of the third quarter of this year, adding that the team inherited a trial “that wasn’t functioning properly” and has focused heavily on improving operational execution and enrollment. He described reallocating medical science liaison resources away from commercialization and toward patient recruitment, using AI to search databases, and building relationships with physicians and investigators to identify and refer patients to trial sites.

Craig said chronic neutropenia patients “eventually end up with hematologists,” and estimated that about 80% of patients are treated in the community setting, primarily by hematologists.

He also flagged a study-design limitation: in consultation with the FDA, the Phase 3 trial uses fixed G-CSF dosing, meaning it will not generate data on how to titrate G-CSF when used with mavorixafor. Craig said X4 is discussing a small Phase 2 study to explore G-CSF titration alongside mavorixafor, with an objective of having published treatment guidance by the time of a potential chronic neutropenia approval, which he said “should be in 2028.”

On safety, Craig said the independent data monitoring committee met last quarter and did not recommend changes. He said he reviews blinded safety data monthly and has not seen new safety signals, though he noted gastrointestinal toxicity that may require symptomatic treatment.

Looking ahead, Craig cited several items as potential investor-focused milestones for the year: an enrollment update, a potential plan for a G-CSF titration study, and a presentation to investors on the market opportunity and supporting work. He said he expects to provide a clearer update later in the year as the impact of operational changes becomes more apparent.

On pricing, Craig said the company has not completed formal pricing research but believes reduced infections and avoided hospitalizations could support premium pricing in a rare disease setting. He added that he does not expect pricing to remain at the current level associated with WHIM—“in the $500,000 range”—and expects it to be lower for chronic neutropenia, while still potentially “very healthy.”

Craig said X4 is not aware of other competitors in development for chronic neutropenia at this time. He acknowledged interest in additional indications—including secondary neutropenias and potentially milder chronic neutropenia—but said the current priority is establishing a “beachhead” in severe and moderate chronic neutropenia before expanding.

About X4 Pharmaceuticals (NASDAQ:XFOR)

X4 Pharmaceuticals, Inc is a clinical-stage biopharmaceutical company focused on the development of novel therapies targeting the C-X-C chemokine receptor type 4 (CXCR4) for the treatment of rare immunological diseases and oncology indications. The company’s lead asset, mavorixafor, is an orally administered, selective small-molecule CXCR4 antagonist designed to mobilize white blood cells and enhance immune function, with a primary focus on WHIM syndrome, a rare congenital immunodeficiency.

Beyond its WHIM syndrome program, X4 is advancing mavorixafor in clinical trials for additional hematologic and solid tumor settings—such as Waldenström’s macroglobulinemia and chronic lymphocytic leukemia—where modulation of the CXCR4 pathway may improve patient outcomes.