Graphite Bio, Inc. announced the presentation of preclinical data for GPH101, an investigational therapy designed to directly correct the genetic mutation responsible for sickle cell disease (SCD). Data were presented at the 49th Annual Sickle Cell Disease Association of America (SCDAA) National Convention in a poster presentation. Graphite Bio presented data establishing the reproducibility of the company’s gene editing platform to generate gene-corrected hematopoietic stem cells (HSCs) for the treatment of SCD. Using Graphite Bio’s gene correction platform, which uses an engineered high fidelity Cas9 to reduce off-target cleavage by 30-fold, the company was able to achieve greater than 60% of gene-corrected beta-globin alleles in vitro with minimal off-target activity. After transplant into mice, long-term engraftment (16 weeks) of gene-corrected cells in vivo was achieved, with gene correction frequencies much greater than the predicted curative threshold of 15% gene correction, which is equivalent to 20% cell correction. These correction frequencies support the potential for this approach to be equivalent or superior to allogeneic hematopoietic stem cell transplant (allo-HSCT) in restoring the expression of normal adult hemoglobin and red blood cell biology. Additionally, the data showed that gene-corrected red blood cells went from producing 100% sickle hemoglobin to expressing more than 90% normal adult hemoglobin. Long-term preclinical safety data revealed no evidence of abnormal hematopoiesis, genotoxicity or tumorigenicity, including no detectable chromosomal translocations. These preclinical data support Graphite Bio’s CEDAR clinical trial, a Phase 1/2 study evaluating the safety, pharmacodynamics, engraftment success, gene correction rates and total hemoglobin, as well as other clinical and exploratory endpoints of GPH101 in patients with severe SCD.