X4 targets year-end start for phase 3 WHIM trial after determining dose in midphase readout

X4 Pharmaceuticals has established the X4P-001-RD dose to take forward into the pivotal stage of its phase 2/3 WHIM syndrome trial. Setting the dose of the CXCR4 inhibitor tees X4 up to start the phase 3 portion of the rare primary immunodeficiency disease trial before the end of the year.

WHIM, an acronym of warts, hypogammaglobulinemia, immunodeficiency and myelokathexis, is a rare syndrome that renders people susceptible to fatal bacterial infections. X4 thinks X4P-001-RD can help these patients by countering the overactive CXCR4 signaling that underpins the syndrome. That could correct patient’s immune system dysfunctions and thereby improve their prospects.

The ongoing open-label phase 2/3 trial is yet to validate the hypothesis. But with biomarkers trending in the right direction and the safety data coming in fairly clean, X4 has seen enough to commit to pushing into the next stage of development.

Of the eight patients treated as of the March cutoff, all experienced dose-dependent increases in circulating neutrophils and lymphocytes. WHIM patients suffer from abnormally low levels of both types of white blood cell as a result of the retention of leukocytes in bone marrow. As such, X4 thinks increased levels of the white blood cells will correlate to improved clinical outcomes.     

Investigators may have seen the first sign of that happening in the phase 2—one patient experienced an improvement in warts—but the truer test will come once X4 moves into phase 3 later in the year.   

The targeted start date for the phase 3 portion of the study continues the rapid rise of X4P-001-RD. The candidate is a formulation of X4P-001, the drug X4 set out to advance in cancer in 2015 when it raised a $37.5 million series A round. Cancer remained X4’s top priority over the next couple of years. But in that time, it saw a chance to truncate its path to market by branching out into WHIM.  

X4 filed to run a phase 2/3 trial late in 2016. If all goes to plan, the biotech will move into the phase 3 portion of the study within two years of publicly expressing an interest in the indication.