The investigational gene editing therapy GPH101 for sickle cell disease is cleared for clinical testing

GPH101 (Graphite Bio Inc.) is an investigational gene-editing autologous hematopoietic stem cell (HSC) therapy designed to directly correct the genetic mutation that causes sickle cell disease (SCD). Preclinical data presented at Sickle Cell Disease Association of America 49th Annual National Convention 2021 highlights the potential of GPH101 to correct the underlying disease-causing mutation to decrease production of sickle hemoglobin and restore the expression of normal adult hemoglobin with minimal off-targeting, thereby supporting the initiation of Graphite Bio’s Phase 1/2 CEDAR clinical trial to evaluate GPH101 in SCD. The company plans to enroll the first patient before the end of the year. Briefly, GPH101 has the potential to achieve over 60% of gene-corrected beta-globin alleles in vitro with a reduced off-target cleavage by 30-fold, and achieve long-term engraftment (16 weeks) of gene-corrected cells in vivo (NSG mice) with no evidence of genotoxicity, abnormal hematopoiesis, or tumorigenicity, including no detectable chromosomal translocations. In addition, the data showed that gene-corrected red blood cells went from producing 100% sickle hemoglobin to expressing more than 90% normal adult hemoglobin. A copy of the poster presentation is available here. For more information: Graphite Bio’s press release