Graphite Bio, Inc.Graphite Bio, Inc. (NASDAQ:GRPH), a clinical-stage, next-generation gene editing company focused on therapies that harness targeted gene integration to treat or cure serious diseases, today presented a trial-in-progress poster for the company’s Phase 1/2 CEDAR trial for GPH101, an investigational therapy designed to directly correct the genetic mutation responsible for sickle cell disease (SCD). The poster is being presented at the 63rd American Association of Hematology (ASH) Annual Meeting and Exposition taking place virtually and at the Georgia World Congress Center in Atlanta from December 11-14. GPH101 was recently granted orphan drug designation from the U.S. Food and Drug Administration (FDA).
“Sickle cell disease is a devastating illness for which a cure is desperately needed. By directly correcting the mutation that causes sickle cell disease, we believe that GPH101 has the potential to be a one-time cure that restores normal physiology and alleviates the life-threatening morbidities associated with the disease,” said Josh Lehrer, M.Phil., M.D., chief executive officer at Graphite Bio. “We are excited to share details about our CEDAR clinical trial for GPH101, in which we recently enrolled our first patient, and we look forward to continuing to advance GPH101’s development in anticipation of sharing initial proof-of-concept data by the end of next year.”
The trial-in-progress poster is being presented by Julie Kanter, M.D., associate professor of medicine and co-director of the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham and an investigator in the CEDAR trial.
“While allogeneic transplant is the only available cure for sickle cell disease, the procedure has several limitations, mainly lack of available donors and risk of graft-versus-host disease. Other available therapies are considered palliative as they do not specifically reverse end-organ damage. This type of gene therapy – reducing sickle hemoglobin production at the same time as restoring adult hemoglobin expression through direct gene correction – would be an ideal curative option in sickle cell disease,” said Dr. Kanter. “As an investigator in the CEDAR trial, I look forward to assessing GPH101’s potential to be a curative option for patients.”
The CEDAR trial is an open-label, single-dose, multi-site clinical trial evaluating GPH101 in approximately 15 participants with severe SCD. GPH101 is an autologous hematopoietic stem cell therapy developed using Graphite Bio’s next-generation targeted gene integration platform, which uses high-fidelity Cas9 and a non-integrating DNA template to precisely find the genetic mutation in the beta-globin gene and directly correct the mutation through the cell’s natural homology directed repair (HDR) cellular pathway. GPH101 has demonstrated in preclinical studies the potential to permanently reduce sickle hemoglobin (HbS) production and restore adult hemoglobin (HbA) expression. The trial-in-progress poster provides an overview of the GPH101 treatment process, which includes local stem cell selection and cryopreservation before shipment to a central manufacturing facility.
The primary objective of the CEDAR trial is to evaluate the safety of GPH101. Secondary objectives include pharmacodynamic and efficacy read-outs such as levels of HbA, HbS and total hemoglobin and effect on clinical manifestations such as vaso-occlusive crisis and acute chest syndrome. Additionally, characterization of gene correction rates, changes in the function of organs like the brain, heart, kidney and liver, and assessment of red blood cell health and function will be explored.