Our Focus: Overview

Developing best-in-disease, gene-edited, hematopoietic stem cell-based therapies

Graphite Bio’s emerging therapeutic pipeline is focused on developing best-in-disease curative genetic therapies for patients suffering from serious diseases. The Graphite Bio gene editing platform uses a site-directed approach to precisely correct genetic defects or insert new genes which can correct the underlying causes of genetic diseases. This novel approach holds broad potential in applications well beyond genetic diseases by engineering disease-fighting functions into cells.

Targeted Integration: The Next Revolution of Gene Editing

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 make a meaningful difference in patients’ lives. The Company is uniting advancements in hematopoietic stem cell (HSC) transplantation and gene editing to ultimately create next-generation therapies with broad potential.

Initially, Graphite Bio is focused on correcting genetic defects and inserting genes within HSCs, which are the somatic stem cells that give rise to all blood and immune cells for the lifetime of an individual. The corrected self-renewing HSCs, once reinfused into patients, are able to differentiate into the appropriate blood and immune cells with restored function – providing the promise of long-term disease remissions and even cures.

Graphite Bio’s gene editing platform repairs genetic defects at their source by combining exquisite targeting of the gene editing machinery to genomic locations with DNA mutations, along with a DNA donor template that harnesses a cell’s own high-fidelity DNA repair mechanism called homology directed repair (HDR). The platform works similar to a computer’s “cut” and “paste” functions, CRISPR precisely cuts the mutated DNA in the defective gene or targeted location and the HDR process, utilizing the Graphite Bio DNA template, then “pastes” in the new DNA to correct the defect or insert a new gene.

Graphite Bio’s first clinical candidate, GPH101, is for sickle cell disease (SCD) and is anticipated to enter clinical testing in 2021 in the CEDAR trial. CEDAR is a Phase 1/2, multi-center, open-label clinical study designed to evaluate the safety, preliminary efficacy and pharmacodynamics of GPH101 in adult and adolescent patients with severe SCD. An inherited blood disorder affecting 100,000 Americans and millions of people worldwide, SCD is caused by a single mutation in the ß globin gene that leads to damaged and misshapen red blood cells resulting in anemia, blood flow blockages, intense pain, increased risk of stroke and organ damage, and reduced life span. Graphite Bio is the first company advancing a potentially curative genetic therapy into the clinic for SCD that aims to fully correct the underlying disease-causing mutation and lead to the production of normal red blood cells with normal hemoglobin.