First multi-patient data show precise sickle cell gene correction restores adult haemoglobin
Kamau Therapeutics has reported that all three patients treated with its nula-cel therapy in the RESTORE trial became transfusion-independent with no pain crises, as precise correction of the sickle cell mutation restored a predominantly adult haemoglobin profile.
A California biotechnology company has reported the first multi-patient clinical data for a therapy that precisely corrects the mutation behind sickle cell disease, rather than working around it, with all three patients treated with its updated manufacturing process becoming free of blood transfusions.
Kamau Therapeutics announced the results on 4 November 2026 from the ongoing Phase 1/2 RESTORE trial of nula-cel, an experimental treatment that engineers a patient's own blood stem cells outside the body and returns them by a single infusion. The data are to be presented in full at the American Society of Hematology annual meeting in New Orleans in December.
Sickle cell disease is caused by a single-point mutation in the beta-globin gene, which makes red blood cells sickle, break down and block blood vessels, causing severe pain crises, anaemia and organ damage. Nula-cel uses homology-directed repair, a form of gene editing, to replace the faulty sickle haemoglobin allele with a healthy copy, one for one, so the edited cells produce normal adult haemoglobin under the body's own regulation.
That direct approach sets it apart from the already approved gene therapy Casgevy, which overcomes the mutation indirectly by switching back on production of foetal haemoglobin. Kamau's co-founder, Stanford physician-scientist Matthew Porteus, has argued that correcting the underlying mutation itself is the more durable route, and the new data are the first test of that claim in more than one patient.
The RESTORE trial, registered as NCT04819841, is a single-arm, open-label study in adults with severe sickle cell disease, enrolling about 15 participants who receive one infusion of nula-cel after myeloablative busulfan conditioning, a chemotherapy step that clears space in the bone marrow for the edited stem cells to engraft.
In the three patients treated with the revised V2.0 manufacturing process, all achieved transfusion independence before leaving hospital, and none has had a vaso-occlusive event, the painful blockages that define the disease, since infusion. Neutrophil engraftment, the return of infection-fighting white blood cells, came at a median of 21 days, ranging from 19 to 32 days.
The haemoglobin numbers are the centrepiece of the announcement. In the two patients with more than six months of follow-up, total haemoglobin rose above 10 grams per decilitre, reaching 10.2 and 11.1, while sickle haemoglobin fell below 20 per cent, to 17.6 per cent at 12 months and 19.1 per cent at eight months. Adult haemoglobin predominated, at 76.8 per cent and 66.8 per cent respectively, and single-cell analyses found more than 90 per cent of circulating red blood cells carried protective levels of anti-sickling haemoglobin.
The company also reported continued follow-up of the very first patient ever treated with nula-cel, under an earlier V1.0 process, who is now four years beyond infusion, a longer horizon that will matter greatly when the full data are scrutinised, since durability is the central question for any one-time gene therapy.
The full results will be presented by John F. DiPersio of Washington University School of Medicine on 14 December, in a session titled on the precise correction of the beta-globin gene by homology-directed repair. Nula-cel has already received Fast Track and Orphan Drug designations from the United States Food and Drug Administration, which allow closer regulatory engagement for a serious condition with unmet need.
Caution is still essential. Three patients are a very small cohort, the results so far come from a conference abstract rather than a peer-reviewed paper, and longer-term safety, including any risk from the conditioning chemotherapy and from the editing process itself, cannot be judged from this early readout. Kamau says it is now enrolling more patients at full speed and moving towards discussions with regulators about the design of a registration trial, which will decide whether this precise correction approach can become a treatment rather than a promising experiment.
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