CK0804 Receives FDA Orphan Drug Designation for Myelofibrosis

The FDA has granted orphan drug designation to the first-in-class, allogeneic, CXCR4^hi regulatory T-cell (Treg) therapy CK0804 for the treatment of myelofibrosis.¹

This regulatory decision is supported by data from 13 patients treated in a phase 1 trial (NCT05423691). Findings from the dose-intensive expansion cohort, as well as 1-year follow-up data from the safety run-in cohort of this study, were presented during the 2025 ASH Annual Meeting and Exposition.^1,2 Treatment with CK0804 led to a spleen volume reduction greater than 10% in 45% of evaluable patients (n = 11) who had experienced disease progression on JAK inhibitors; symptom burden reduction greater than 50% in 78% of evaluable patients (n = 9); and improvement in transfusion burden in all 3 evaluable patients.

"Receiving orphan drug designation is an important milestone in the clinical development of CK0804 for myelofibrosis and underscores our commitment to advance CK0804 into phase 2 trials to address the unmet need for patients who have not responded to currently available therapies", Simrit Parmar, MD, founder of Cellenkos, stated in a news release.¹ "The observed increase in interleukin 10 [IL-10] and decreases in TGFβ levels in CK0804 responders, together with reductions in pathogenic monocytes in plasma and bone marrow, support the disease-modifying potential of CK0804 Tregs as a distinct and differentiated therapeutic class in myelofibrosis."

CK0804 is an investigational, allogeneic, off‑the‑shelf therapy composed of CXCR4^hi Tregs that selectively traffic to gradients of its ligand, CXCL12. In patients with myelofibrosis, this ligand is overexpressed in the bone marrow and at sites of extramedullary hematopoiesis, such as the spleen.

After homing in to target tissues, CK0804 Tregs interact with antigen-presenting cells, undergo in vivo expansion, and secrete IL-10. This engenders the resolution of inflammation through a nonmajor histocompatibility complex–dependent mechanism while modulating platelet-derived growth factor–driven pathways implicated in disease remodeling.

Preclinical studies have demonstrated that CXCR4-enriched Tregs preferentially migrate to the bone marrow and suppress proinflammatory cytokine signaling, and preliminary efficacy signals have been previously reported in myelofibrosis.

What was the design of this phase 1 study?

This phase 1 study is evaluating the safety, tolerability, and preliminary activity of CK0804 as an add-on to steady-dose ruxolitinib (Jakafi) in patients 18 years of age or older with primary myelofibrosis or post–polycythemia vera or essential thrombocythemia myelofibrosis who had experienced a suboptimal response on ruxolitinib.^2,3 Ruxolitinib must have been administered for at least 12 weeks, with a stable dose for the preceding 8 or more weeks. Patients could have palpable splenomegaly at least 5 cm below the costal margin; active myeloproliferative neoplasm symptoms; and grade 2 or higher anemia/thrombocytopenia. An ECOG performance status between 0 and 2 and adequate hematologic and organ function were also required.

Of the 13 patients enrolled onto the study, 9 received CK0804 on a monthly infusion schedule and 4 received the agent on a dose‑intensive regimen consisting of weekly infusions for 4 weeks followed by monthly infusions for 5 additional doses, with a fixed number of 100 million Tregs per infusion.² The median age of enrolled patients was 68 years (range, 55-84), and patients had received a median of 2 prior lines of therapy (range, 1-6).¹

What additional efficacy, safety, and pharmacokinetic data were reported from this study?

Additional results showed that 10 patients were alive at a median follow‑up of 195 days (range 41-809).¹ Of these, 3 patients proceeded to stem cell transplant, 2 switched to a different class of therapy, and 5 continued their initial treatment with ruxolitinib.

In the thrombocytopenic subgroup, all 3 patients tolerated the intensive CK0804 regimen; all had a 100% reduction in symptom burden, and 2 achieved a spleen volume reduction of at least 10%.⁴

Notably, CK0804 responders demonstrated decreased circulating levels of TGFβ1, TGFβ2, FGF, PDGF, and sCD40L, reduced plasma and bone marrow monocytes, and normalization of the bone marrow myeloid‑to‑erythroid ratio.¹ CK0804 Tregs also improved packed red blood cell transfusion requirements, and CK0804 Treg–induced responses lasted over 1 year after treatment cessation.

Next steps for this research include the initiation of a phase 2 study evaluating CK0804 in patients with JAK inhibitor–resistant/suboptimal myelofibrosis.⁴

References

1. FDA grants orphan drug designation to Cellenkos' CK0804 Treg therapy for treatment of myelofibrosis. News release. Cellenkos. January 6, 2026. Accessed January 6, 2026. https://www.prnewswire.com/news-releases/fda-grants-orphan-drug-designation-to-cellenkos-ck0804-treg-therapy-for-treatment-of-myelofibrosis-302653827.html
2. Masarova L, Abedi M, Pemmaraju N, et al. Dose intensive regimen of CK0804 Tregs in myelofibrosis. Blood. 2025;146(suppl 1):5602. doi:10.1182/blood-2025-5602
3. Leading in MPNs beyond ruxolitinib in combo with T-regs (TREG108). ClinicalTrials.gov. Updated April 13, 2025. Accessed January 6, 2026. https://www.clinicaltrials.gov/study/NCT05423691
4. Dose-intensive CK0804 regimen reduces spleen volume and transfusion needs in JAK inhibitor-resistant/suboptimal myelofibrosis with thrombocytopenia. News release. Cellenkos. December 10, 2025. Accessed January 6, 2026. https://www.prnewswire.com/news-releases/dose-intensive-ck0804-regimen-reduces-spleen-volume-and-transfusion-needs-in-jak-inhibitorresistant-suboptimal-myelofibrosis-with-thrombocytopenia-302637978.html