FDA Grants Orphan Drug Designation to CK0804 in Myelofibrosis

CK0804, an investigational allogeneic regulatory T cell (Treg) therapy, has received orphan drug designation (ODD) from the FDA for the treatment of myelofibrosis.¹

ODD is granted to agents in development for prevention or treatment of rare diseases and conditions affecting less than 200,000 patients in the US.² Myelofibrosis, a rare myeloproliferative neoplasm, is characterized by altered bone marrow function, fibrosis, spleen enlargement, significant inflammation, and fatigue, greatly impacting patients’ quality of life.³

The intravenously administered CK0804 leverages targeted immune regulation to address inflammation driven by the disease. The agent is made of CXCR4^hi Tregs that are drawn to CXCL2, a chemokine highly expressed in the bone marrow and extramedullary hematopoietic tissues including the spleen. Once in the affected tissue, the cells interact with antigen-presenting cells, proliferate in vivo, and secrete and deliver the anti-inflammatory cytokine interleukin-10 (IL-10).

"Receiving [ODD] 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," said Simrit Parmar, MD, of Cellenkos, in a news release.¹ "The observed increase in 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."

With this designation, Cellenkos, the sponsor, will be eligible for incentives including tax credits for clinical trials, user fee exemptions, and a potential 7 years of market exclusivity upon approval.

CK0804: Early Clinical Data

A phase 1 trial (NCT05423691) in the United States is currently investigating the safety, tolerability, and preliminary activity of CK0804 as add-on therapy to steady-dose ruxolitinib (Jakafi).⁴ The trial is accruing an estimated 24 patients with myelofibrosis, including primary myelofibrosis and myelofibrosis arising from polycythemia vera and essential thrombocythemia, who have had a previous inadequate response to ruxolitinib.

Initial results from the safety run-in portion were read out in 2024. This portion, which aimed to assess the safety and tolerability of up to 6 doses of the treatment, demonstrated CK0804’s generally well-tolerated safety profile, with no myelosuppressive adverse events (AEs).⁵ Additionally, 4 of 6 evaluable patients at the time had experienced spleen volume reduction.

The FDA’s designation follows a recent presentation of updated data from the study’s safety run-in and expansion cohort at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition. Here, findings from the expansion cohort showed a reduction in symptom burden and no occurrence of grade 3 or 4 treatment-related AEs after 28 infusions of CK0804.⁶

Additional data from the safety run-in showed a 49% average decrease in symptom burden, notably fatigue and early satiety, among those who responded to therapy. Furthermore, there was evidence of reduction of pro-inflammatory cytokines, as well as an increase in the anti-inflammatory IL-10 in most patients, indicating favorable shifts in patients’ immune system following treatment with CK0804.

Next Steps in Development

The early clinical data suggest that CK0804 could emerge as a differentiated option for patients with limited benefit from current standard therapies. If confirmed in later-stage trials, the agent may help address a significant unmet need in myelofibrosis and potentially broaden the role of Treg-based therapies in hematologic malignancies.

As revealed by Parmar, the sponsor intends to advance CK0804 into phase 2 trials to further evaluate its therapeutic potential. These trials will be critical to validating preliminary efficacy signals and further establishing CK0804’s clinical niche for patients with this rare disease.

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://tinyurl.com/4sfwftm3

2. Designating an orphan product: drugs and biological products. US Food & Drug Administration. Updated August 12, 2024. Accessed January 6, 2026. https://tinyurl.com/5n77pu2w

3. Breccia M, Palandri F, Polverelli N, et al. Epidemiology and disease characteristics of myelofibrosis: a comparative analysis between Italy and global perspectives. Front Oncol. 2024;14:1382872. Published 2024 Jul 24. doi:10.3389/fonc.2024.1382872

4. 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

5. Masarova L, Huang M, Goel S, et al. A phase Ib, open-label study of add-on therapy with CK0804 in participants with myelofibrosis and suboptimal response to ruxolitinib. Blood. 2024;144(Supplement 1):999-999. doi:10.1182/blood-2024-211587

6. Masarova L, Abedi M, Pemmaraju N, et al. Dose intensive regimen of CK0804 tregs in myelofibrosis. Blood. 2025;146(Supplement 1):5602-5602. doi:10.1182/blood-2025-5602