Graphite Bio is a biotechnology company focused on developing gene editing therapies. Established to address serious and life-threatening conditions, their work centers on precise gene editing techniques, offering a unique approach to correct underlying genetic defects.
Understanding Graphite Bio
Graphite Bio, founded in 2018, is a clinical-stage biotechnology company dedicated to developing cures for a range of severe diseases. The company’s core mission involves advancing gene editing technologies to repair or replace damaged genes. Within the broader landscape of genetic medicine, Graphite Bio strives to develop transformative therapies by targeting the root causes of inherited disorders.
Its foundational purpose is to pioneer a precision gene editing approach that can transform human health by precisely “finding and replacing” any gene in the genome. Its focus on precision gene editing and clinical-stage status distinguishes it.
Their Approach to Gene Editing
Graphite Bio’s gene editing technology is built upon the principle of homologous recombination, a natural cellular DNA repair process. Their platform, known as UltraHDR™, aims to move beyond simple gene cutting, harnessing high-efficiency precision DNA repair to accurately correct genetic mutations.
This method allows for the precise correction of genetic defects, replacement of entire disease-causing genes with functional ones, or the insertion of new genes into specific, safe locations within the genome. The company’s approach seeks to replace defective genes at their original chromosomal location, enabling the production of normal gene expression within the modified cells. This targeted gene integration aims for durable expression while minimizing toxicity from insertions in unintended places.
The technology, developed at Stanford University, incorporates tools to achieve targeted and permanent DNA integration with high efficiency. Studies have demonstrated an increase in integration efficiency from less than 1% to greater than 50% across various genetic lesions and cell types. This improved efficiency is important for therapeutic applications.
Diseases Under Investigation
Graphite Bio has historically focused its gene editing efforts on several specific genetic diseases. Their lead program targeted sickle cell disease (SCD) with a therapy known as nulabeglogene autogedtemcel, or nula-cel. SCD is a serious inherited blood disorder caused by a single-point mutation in the beta-globin (HBB) gene, affecting millions globally.
The therapeutic strategy for nula-cel aimed to correct this specific mutation in patient-derived hematopoietic stem cells. The goal was to decrease the production of sickle hemoglobin and restore healthy adult hemoglobin expression. Other conditions previously under investigation included beta-thalassemia with therapy GPH102, X-linked severe combined immunodeficiency (XSCID), and Gaucher disease (Types 1 and 3).
Clinical Development and Outlook
Graphite Bio initiated a Phase 1/2 clinical trial, known as CEDAR, for its lead candidate, nula-cel, in sickle cell disease. The first patient in this study was dosed in August 2022. In January 2023, the company voluntarily paused the CEDAR study following a serious and unexpected adverse event in the first patient, specifically prolonged low blood cell counts requiring ongoing support.
The company concluded the event was related to the treatment. In February 2023, Graphite Bio announced the discontinuation of nula-cel’s development and stated it would seek a partnership for external development. This decision was based on the resources needed to resume the CEDAR study and the evolving treatment landscape for sickle cell disease.
In December 2023, Kamau Therapeutics emerged, acquiring an option to obtain Graphite Bio’s genome editing assets, including the platform technology and the nula-cel program. Kamau Therapeutics intends to continue studying nula-cel, with data from the first patient being presented at the American Society of Hematology annual meeting.