Positive Results from Six-Month Phase 2 Trial of Mavorixafor in Chronic Neutropenia
On November 13, 2024, X4 Pharmaceuticals, Inc. (NASDAQ:XFOR) announced positive topline results from the Phase 2 trial of mavorixafor in patients with chronic neutropenia (CN). This was a six-month, open label trial that enrolled a total of 23 participants diagnosed with either idiopathic, congenital, or cyclic CN. There were two study groups in the trial: mavorixafor monotherapy (n=10 at baseline) and mavorixafor in combination with granulocyte colony-stimulating factor (G-CSF; n=13 at baseline). The following slide give an overview of the study population.
The results showed that for the 10 participants on mavorixafor monotherapy there was a durable and meaningful increase in absolute neutrophil count (ANC). The figure on the left shows that for all participants, the mean ANC was ≥ 1,500 cells/µL after three and six months of treatment. The figure on the right shows that participants with severe CN (defined as an ANC ≤500 cell/µL) on mavorixafor monotherapy achieved >2x baseline mean ANC through Month 6.
In the mavorixafor + G-CSF cohort, of 12 eligible patients (one patient withdrew from the study prior to the Month 1 assessment) nine had their G-CSF reduced and three of them were taken off G-CSF prior to the Month 6 visit. The following graph shows the reduction in G-CSF over time. By Month 3, eight participants had an average reduction in G-CSF dosing of 52% while at Month 6, nine participants had an average reduction in G-CSF dosing of 70%. In addition, the mean ANC for those patients was maintained at normal levels (>1,500 cell/µL) through Month 6. Patients and physicians typically report that anything >25% reduction in G-CSF dosing corresponds with clinically meaningful differences in short- and long-term toxicities.
In regards to safety and tolerability, overall the safety profile was similar to what has been seen in prior studies. There were no new safety issues observed when mavorixafor was dosed with G-CSF and there were no deaths or drug-related serious adverse events. The most frequently reported treatment-emergent adverse events (TEAEs) were gastrointestinal (GI) related (nausea and diarrhea).
Phase 3 4WARD Study Ongoing
X4 is continuing participant enrollment in the Phase 3 4WARD trial of mavorixafor in CN patients with congenital, autoimmune, or idiopathic chronic neutropenia. The trial is expected to enroll 150 participants with an ANC <1500 cells/mL and a history of two or more infections requiring intervention in the last 12 months. The primary endpoint is a two-component endpoint based on a positive ANC response and annualized infection rate, with secondary endpoints evaluating severity and duration of infection, antibiotic use, fatigue, quality of life, and safety. Thus far, approximately 40% of planned sites are initiated and we continue to expect enrollment to complete by mid-2025.
Financial Update
On November 13, 2024, X4 announced financial results for the third quarter of 2024. Revenue in the third quarter of 2024 totaled $0.6 million. X4 sells XOLREMDI exclusively to a specialty pharmacy that dispenses the product to patients that have had it prescribed to them. Gross product revenue is recorded based on the amount of drug product delivered to the specialty pharmacy at the wholesale acquisition cost. The cost of revenue for the three months ending September 30, 2024 was $0.2 million.
R&D expenses for the third quarter of 2024 were $19.2 million compared to $19.1 million for the third quarter of 2023. SG&A expenses for the third quarter of 2024 were $15.7 million compared to $8.1 million for the third quarter of 2023. The increase was primarily due to an increase in legal costs, outside consulting fees, and increased sales and marketing expenses as the company continues to build out the sales and marketing infrastructure to support the launch activities of XOLREMDI.
The company exited the third quarter of 2024 with approximately $135.8 million in cash, cash equivalents, restricted cash, and short-term marketable securities. We estimate the company has sufficient capital to fund operations into late 2025, and this estimate does not include any potential future XOLREMDI revenues. As of November 11, 2024, X4 had approximately 170.5 million shares outstanding and, when factoring in stock options, warrants, and restricted stock units, a fully diluted share count of 299.0 million.
Conclusion
The results from the Phase 2 chronic CN trial are encouraging, particularly the large percentage of patients that were able to reduce G-CSF dosing, and these results bolster our confidence in the ongoing Phase 3 4WARD trial. Assuming enrollment continues on the current pace, that trial should be fully enrolled by mid-2025.
Revenues for XOLREMDI this quarter were lower than we had originally projected, however the company shared that 100% of launch targets have been reached (3,400 unique HCPs) and a recent market research report by the company stated that the knowledge of WHIM syndrome has increased >75%, ~60% of HCPs reported increases in screening for WHIM syndrome, and >80% of HCPs would consider prescribing XOLREMDI for WHIM patients. All of these statistics should contribute to a ramp in revenues in 2025, however for now we have lowered projected revenues over the next couple of years and increased the discount rate in our model to account for a slower uptake than originally anticipated. Our valuation is now $3.00 per share.
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