Sickle cell pipeline gets edited down
The pipeline for gene-edited ex vivo projects for sickle cell disease, once full to bursting, now looks a lot less crowded. Three contenders have dropped out of the race in the past two days: Intellia/Novartis’s OTQ923, Graphite’s nula-cel and Sangamo’s BIVV003. The writing was already on the wall for OTQ923 and nula-cel following disappointing data at Ash 2022 and a clinical hold respectively. Intellia is now focused on an in vivo editing approach in sickle cell, which is in preclinical development. Sangamo produced decent data with SAR445136; Sanofi handed back its rights to the project around 12 months ago after deciding to refocus on allogeneic approaches. Sangamo is now looking for a new partner, but the project might be too far behind Crispr/Vertex’s exa-cel to draw much interest. Attention now turns to Editas, which expects to give a mid-year update on the Ruby study of EDIT-301.
| Selected ex vivo gene-edited sickle cell projects in development | |||
|---|---|---|---|
| Project | Company | Description | Status/trial details |
| CTX001 | Crispr/Vertex | Crispr/Cas9 gene-edited cell therapy targeting BCL11a | Filed in EU and UK Dec 2022; US submission expected to conclude by the end of Q1 2023 |
| EDIT-301 | Editas | Crispr/Cas12a gene-edited cell therapy targeting beta-globin to increase foetal haemoglobin | Update from Ph1/2 Ruby trial expected mid-2023 |
| BEAM-101 | Beam Therapeutics | Base-edited cell therapy promoting foetal haemoglobin | Ph1/2 Beacon trial could report 2025 |
| SAR445136 (BIVV003) | Sangamo | Zinc finger nuclease gene-edited cell therapy targeting BCL11a | Ph1/2 Precizn-1 trial will be completed, but no further investment will be made; company seeking a partner for Ph3 trials |
| GPH101 | Graphite Bio | Homology-directed repair gene-edited cell therapy targeting underlying beta-globin mutation | Discontinued following case of pancytopenia in Ph1/2 Cedar trial |
| OTQ923 & HIX763 | Intellia/Novartis | Crispr/Cas9 gene-edited cell therapy targeting BCL11a | Discontinued following poor Ph1/2 data |
| BEAM-102 | Beam Therapeutics | Base-edited cell therapy recreating HbG Makassar variant | Deprioritised in favour of BEAM-101 and other technologies |
| Source: Evaluate Pharma & clinicaltrials.gov. | |||
