Kamau Therapeutics has reported early clinical evidence that its gene-editing therapy nula-cel can correct the sickle cell mutation and restore production of adult haemoglobin.

Results from three patients treated with an optimised manufacturing process in the Phase 1/2 RESTORE trial showed transfusion independence and no vaso-occlusive events following treatment. Two patients followed for more than six months had predominantly adult haemoglobin, with sickle haemoglobin below 20%.

The investigational therapy is designed to correct the disease-causing mutation in the HBB gene using homology-directed repair (HDR), rather than increasing fetal haemoglobin to compensate for the defective gene.

Nula-cel uses a patient’s own blood-forming stem cells. These are collected, genetically corrected outside the body and returned following myeloablative busulfan conditioning.

Gene editing aims to restore normal adult haemoglobin

Sickle cell disease is caused by a mutation in the HBB gene, which produces abnormal haemoglobin S (HbS). HbS can cause red blood cells to become rigid and sickle-shaped, leading to blockages in blood vessels, painful vaso-occlusive episodes and progressive organ damage.

Unlike approaches that increase fetal haemoglobin to reduce the effects of HbS, nula-cel is designed to convert the sickle mutation directly to the normal adult haemoglobin sequence.

In the three patients treated with the revised manufacturing process, all achieved neutrophil engraftment, with a median time of 21 days. All three also achieved transfusion independence before hospital discharge, and no vaso-occlusive events were reported following infusion.

The two patients with more than six months of follow-up had total haemoglobin levels of 10.2 g/dL at 12 months and 11.1 g/dL at eight months. Their HbS levels were 17.6% and 19.1%, respectively, while adult haemoglobin (HbA) accounted for 76.8% and 66.8%.

Bone marrow analysis showed HDR allele frequencies stabilising at approximately 20%, which the company said was consistent with engraftment of gene-corrected stem cells. Single-cell analysis also found that more than 90% of circulating red blood cells contained protective levels of anti-sickling haemoglobin.

John F DiPersio, director of the Center for Gene and Cellular Immunotherapy at Washington University School of Medicine, said: “Achieving hemoglobin levels above 10 g/dL, with sickle hemoglobin below 20% and adult hemoglobin predominant, in patients who also remain free of vaso-occlusive events is an encouraging early signal. Seeing that profile alongside stable engraftment of corrected cells is what we would hope to see from a durable correction of the underlying mutation. These are early data in a small number of patients, and longer follow-up will be essential, but they support continued evaluation of this approach.”

Revised manufacturing process shows early consistency

The results include the first three patients treated using Kamau’s revised V2.0 manufacturing process. Drug product HDR allele frequencies ranged from 32% to 38%, exceeding the company’s 20% target. Patients required a median of one apheresis cycle to reach the target cell dose.

No serious adverse events related to nula-cel or the gene-editing procedure were reported in these three patients. Reported adverse events were consistent with busulfan conditioning and autologous stem cell transplantation, while off-target editing remained low and unchanged.

The company also reported continued follow-up of the first patient treated with nula-cel using its original V1.0 process, who was four years post-infusion at the time of the announcement. These results provide a separate, longer-term observation and should not be confused with follow-up from the three V2.0-treated patients.

Nula-cel receives FDA regulatory designation

Nula-cel is being evaluated in RESTORE, an ongoing Phase 1/2, open-label study designed to assess safety, preliminary efficacy and pharmacodynamic activity in people with severe sickle cell disease.

The clinical findings are due to be presented by DiPersio at the 68th American Society of Hematology Annual Meeting on 14 December 2026.

On 12 November, Kamau announced that the US Food and Drug Administration had granted nula-cel Regenerative Medicine Advanced Therapy (RMAT) designation, based on preliminary clinical evidence from RESTORE. The therapy also holds Fast Track and Orphan Drug designations.

RMAT designation provides opportunities for closer FDA engagement and support during development, but does not mean the therapy has been approved.

The findings represent early clinical evidence for precise correction of the sickle cell mutation. Further patient enrolment and longer follow-up will be needed to establish the durability of the response and assess the therapy’s safety and efficacy in a larger population.