Cellenkos' CK0804 Regulatory T Cell Therapy Shows Promise in JAK Inhibitor-Resistant Myelofibrosis
核心洞察
Cellenkos (搜索)' CK0804 regulatory T cell therapy demonstrated significant clinical benefits in myelofibrosis (搜索) patients who had inadequate responses to JAK inhibitors, with 45% achieving spleen volume reduction of at least 10%.
All three transfusion-dependent patients showed reduced monthly transfusion requirements, while 78% of patients experienced greater than 50% reduction in symptom burden following the dose-intensive regimen.
The therapy showed particular promise in thrombocytopenic patients, with all three achieving 100% reduction in symptom burden and two achieving meaningful spleen volume reduction.
Cellenkos (搜索)' investigational regulatory T cell therapy CK0804 demonstrated promising clinical activity in patients with myelofibrosis (搜索) who had inadequate responses to standard JAK inhibitor (搜索) therapy, according to data presented at the 67th American Society of Hematology Annual Meeting in Orlando, Florida.
The study evaluated 13 patients receiving CK0804, with 11 patients evaluable for efficacy analysis. Among these patients, 45% achieved at least 10% spleen volume reduction (SVR10), 27% achieved SVR25, and 18% achieved SVR35. All three transfusion-dependent patients demonstrated reduced monthly transfusion requirements by study end.
Clinical Outcomes and Patient Response
The dose-intensive regimen showed substantial impact on patient symptoms, with 78% of patients (9 of 11) experiencing greater than 50% reduction in total symptom burden. Clinical responses correlated with reductions in key inflammatory biomarkers including FGF, sCD40L, PDGF-AA, and PDGF-AA/BB.
"Patients almost immediately started to feel better, and they do not want to stop CK0804 infusions," said Mehrdad Abedi, MD, Principal Investigator and Professor of Medicine at University of California, Davis. "Even in patients with thrombocytopenia (搜索) and poor renal function, CK0804 was well tolerated, and patients reported improvements in abdominal distention and early satiety, which paralleled reductions in spleen volume."
Thrombocytopenic Patient Subgroup
The therapy showed particularly encouraging results in the challenging thrombocytopenic patient population. All three thrombocytopenic patients tolerated the intensive CK0804 regimen, achieved 100% reduction in symptom burden, and two patients achieved SVR10. This represents a significant clinical advance given the limited treatment options for this patient subset.
Treatment Protocol and Mechanism
The study employed two dosing regimens: nine patients received monthly infusions, while four patients received a dose-intensive regimen consisting of weekly infusions for four weeks followed by monthly infusions for five additional doses. Each infusion contained a fixed dose of 100 million regulatory T cells.
CK0804 is designed to exploit the CXCR4 (搜索)/CXCL12 (搜索) axis to suppress inflammatory cytokines implicated in myelofibrosis (搜索) pathogenesis. The therapy is derived from clinical-grade umbilical cord blood and manufactured using Cellenkos (搜索)' proprietary CRANE® process.
"Intensifying the CK0804 Treg regimen appears to counter the high inflammatory burden in myelofibrosis (搜索)," said Simrit Parmar, MD, MSCI, Founder of Cellenkos (搜索). "The depth and durability of responses in thrombocytopenic patients who had failed or had suboptimal benefit from prior JAK inhibitor (搜索) therapy are particularly encouraging and pave way for phase 2 trial."
Therapeutic Advantages
The allogeneic, off-the-shelf Treg cell therapy offers several practical advantages. CK0804 does not require HLA matching and is supplied cryopreserved with a shelf life exceeding two years, enabling rapid, on-demand use. The product is administered intravenously through a peripheral line in an outpatient setting.
Cellenkos (搜索)' CRANE® platform isolates highly suppressive, stable Tregs from allogeneic umbilical cord blood. These cord blood-derived Tregs remain stable suppressor cells without converting to pro-inflammatory phenotypes, even in hostile inflammatory environments. The cells express chemokine receptors including CXCR3 (搜索), CXCR4 (搜索), CXCR7 (搜索), and LFA-1 (搜索), allowing precise homing to inflamed tissues.
Next Steps
Based on these encouraging results, Cellenkos (搜索) plans to initiate a phase 2 trial of CK0804 in JAK inhibitor (搜索)-resistant or suboptimal myelofibrosis (搜索) patients. The company operates an in-house cGMP manufacturing facility in Houston, Texas, overseeing the full value chain from process development through clinical supply.