Our Science: Pipeline
Graphite Bio brings an ambitious vision to advance gene editing from the bench to the bedside – transforming our founders’ ground-breaking discoveries into therapies that are intended to make a meaningful difference in patients’ lives. The Company is uniting advancements in hematopoietic stem cell (HSC) transplantation and gene editing with the goal of ultimately creating next-generation therapies with broad potential.
GPH101: Distinct approach in sickle cell disease
Graphite Bio’s first clinical candidate, GPH101, is an investigational next-generation gene-edited autologous HSC product candidate that is designed to directly correct the genetic mutation responsible for sickle cell disease (SCD) and restore normal adult hemoglobin by directly targeting the ß globin gene. With an IND cleared by the U.S. Food & Drug Administration (FDA), GPH101 is anticipated to enter clinical testing in 2021 in the CEDAR trial. CEDAR is a Phase 1/2, multi-center, open-label clinical trial designed to evaluate the safety, engraftment success, gene correction rates, total hemoglobin, as well as other clinical and exploratory endpoints and pharmacodynamics of GPH101 in patients with severe SCD.
Learn more about the Phase 1/2 CEDAR clinical trial here.
GPH201: Novel gene replacement product candidate for XSCID
Graphite Bio is developing GPH201 for the treatment of XSCID, a rare, life-threatening disease where multiple mutations in a single gene (IL2RG) prevent normal immune system function. The company’s gene replacement approach is designed to lead to normal regulated expression of the IL2RG gene. The survival advantage of the progeny of gene edited cells combined with Graphite Bio’s high efficiency of gene replacement could enable patients to benefit from GPH201 without undergoing chemotherapy-based conditioning.
GPH201 is intended to be evaluated with non-genotoxic HSC targeted antibody-based bone-marrow conditioning regimens. GPH201 has the potential to generate preliminary data on combining autologous HSC therapies with non-genotoxic HSC targeted conditioning. Graphite Bio’s clinical experience could accelerate the ability to use non-genotoxic HSC targeted conditioning with the company’s other product candidates.
GPH301: Novel gene replacement product candidate for Gaucher disease
GPH301 is a next generation gene-edited autologous HSC product candidate leveraging the CCR5 locus technology for the treatment of Gaucher disease. With GPH301, a functional copy of the gene for glucocerebrosidase (GCase) is inserted into the chromosomal location of the CCR5 gene. This locus is known as a safe harbor both due to the lack of serious deleterious effects in humans with CCR5 mutations and because the expression of genes inserted there can be precisely controlled by regulatory elements inserted together with the gene of interest.
Graphite Bio intends to develop GPH301 for the treatment of both Type 1 and Type 3 Gaucher disease. Type 3 disease will likely require standard chemotherapy-based conditioning. In Type 1 disease, Graphite Bio will explore targeted conditioning regimens. This same approach can be used for production of therapeutic proteins for other diseases including other lysosomal storage diseases. Proof of concept in Gaucher may accelerate development of a pipeline of CCR5 safe harbor protein production candidates.