Business Overview

Positive Interim Update for Phase 2 Chronic Neutropenia Trial

On June 27, 2024, X4 Pharmaceuticals, Inc. (NASDAQ:XFOR) held a webinar to provide an interim update for the ongoing Phase 2 clinical trial of mavorixafor in patients with chronic neutropenia (CN). The Phase 2 study is fully enrolled with 23 participants across three groups: mavorixafor monotherapy, mavorixafor + stable-dose G-CSF, and mavorixafor + G-CSF with dose-adjustments.

All six participants achieved the target increase in absolute neutrophil count (ANC) of ≥ 500 cells/µL by month 6. For the mavorixafor monotherapy group, the results showed a durable increase in mean ANC across that cohort, with the average ANC for the group starting in what would be considered "moderate neutropenia" and by month six the average participant exceeded the lower limit of normal. For the mavorixafor + stable-dose G-CSF cohort, the results showed a robust increase in ANC with a mean increase of >1,000 cells/µL from baseline at all timepoints. Mavorixafor was well tolerated as both a monotherapy and in combination with G-CSF, as there were no deaths or drug-related serious adverse events reported.

Phase 3 4WARD Study Initiated

X4 has initiated participant screening for 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 <1,500 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.

Financials

In May 2024, X4 announced it completed the sale of its Rare Pediatric Disease Priority Review Voucher (PRV) for $105 million. In addition, the company drew down an additional tranche of $20 million under its existing loan facility with Hercules Capital. This infusion of capital has extended the company's cash runway into late 2025, which does not include revenues from expected commercial sales of XOLREMDI™.

For the first quarter of 2024, X4 reported a net loss of $51.8 million, compared to a net loss of $24.0 million in the same period of 2023. Research and development expenses were $19.9 million in Q1 2024, compared to $22.1 million in Q1 2023. Selling, general and administrative expenses were $17.4 million in Q1 2024, compared to $7.2 million in Q1 2023. As of March 31, 2024, the company had $81.6 million in cash, cash equivalents, restricted cash and short-term marketable securities.

Conclusion

The positive interim update from the ongoing Phase 2 trial of mavorixafor in CN patients is encouraging. No new safety issues were identified, 100% of patients achieved the target increase in ANC after six months of treatment, and the robust increase in ANC in patients receiving mavorixafor + G-CSF supports the potential for decreasing the G-CSF dose. The company's financial position has been strengthened by the sale of the PRV and additional debt financing, extending the cash runway into late 2025. However, the pace of enrollment for the Phase 3 trial may be a concern for investors, which the company hopes will be mitigated by the greater number of clinical sites across multiple countries. Overall, the reaction in the stock since the interim update has been overdone and represents a nice buying opportunity for long-term investors.

X4 Pharmaceuticals is a biopharmaceutical company discovering, developing, and commercializing novel therapeutics for the treatment of rare diseases and those with limited treatment options, with a focus on conditions resulting from dysfunction of the immune system. The company's lead product candidate, mavorixafor, is an orally active bioavailable selective antagonist of chemokine receptor CXCR4, a key regulator of the movement of immune cells throughout the body.

In April 2024, the FDA approved mavorixafor, which is being marketed under the trade name XOLREMDI™, for use as an oral, once-daily therapy in patients 12 years of age and older with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, to increase the number of circulating mature neutrophils and lymphocytes. WHIM syndrome is a rare combined primary immunodeficiency and chronic neutropenic disorder. The company is currently engaged in the U.S. launch of XOLREMDI in WHIM syndrome while also planning to seek regulatory approvals to commercialize mavorixafor outside of the U.S.

Due to mavorixafor's ability to increase the mobilization of white blood cells from the bone marrow into the bloodstream, the company believes that it has the potential to provide therapeutic benefit across a variety of immune system disorders in addition to WHIM syndrome. As a result, the company is conducting a Phase 2 clinical trial evaluating the safety and efficacy of mavorixafor as a monotherapy and in combination with human granulocyte colony-stimulating factor (G-CSF) in people with certain chronic neutropenic disorders. Interim data from this Phase 2 trial are expected to be presented in June 2024.

The company also plans to initiate a global Phase 3 clinical trial of mavorixafor in the second quarter of 2024 that aims to evaluate the efficacy, safety, and tolerability of oral once-daily mavorixafor with or without G-CSF in people with congenital or acquired primary autoimmune and idiopathic chronic neutropenia who are experiencing recurrent and/or serious infections.

For the full year 2023, X4 Pharmaceuticals reported a net loss of $101.2 million, with no revenue generated. The company's operating cash flow for 2023 was -$96.5 million, and its free cash flow was -$96.6 million. As of March 31, 2024, the company had $81.6 million in cash, cash equivalents, restricted cash and short-term marketable securities.

The company's success will depend on its ability to successfully commercialize XOLREMDI in the U.S. and obtain regulatory approvals to commercialize mavorixafor in other markets, as well as advance the development of mavorixafor for the treatment of chronic neutropenic disorders. Key risks include the ability to enroll patients in clinical trials in a timely manner, obtain regulatory approvals, manage the commercial launch of XOLREMDI, and secure additional funding to support the company's operations and development programs.

Overall, the positive interim data from the Phase 2 chronic neutropenia trial and the company's strengthened financial position provide a solid foundation for X4 Pharmaceuticals to advance the development of mavorixafor and potentially expand its commercial opportunity beyond the WHIM syndrome indication. The upcoming Phase 3 trial in chronic neutropenia will be a critical next step in demonstrating the broader potential of this novel CXCR4 antagonist.