Biotech Spotlight: Graphite Bio seeks sickle cell cure with a next-gen approach

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Welcome to Biotech Spotlight, a series featuring companies with breakthrough technologies and strategies. Today, we’re looking at Graphite Bio, a gene editing company advancing a treatment for sickle cell disease that makes use of precise methods of targeted gene integration.

Graphite Bio CEO Josh Lehrer

Graphite Bio CEO Josh Lehrer

Permission granted by Graphite Bio/Josh Lehrer

In focus with: Josh Lehrer, Graphite Bio CEO

Graphite Bio’s vision: With it’s gene editing platform, Graphite is seeking to bring its lead candidate for sickle cell disease through early stage clinical trials, as well as preclinical therapies for other genetic conditions like beta-thalassemia, alpha-1 antitrypsin deficiency, X-linked severe combined immunodeficiency. syndrome and Gaucher disease. CEO Josh Lehrer also believes the company’s platform could be used in collaboration with other companies to augment their gene editing capabilities.

Why it matters: CRISPR gene editing technology is still a rather new development in the life sciences, and many companies are looking to harness its potential to treat and even cure genetic diseases. Among those conditions is sickle cell disease, which affects almost 6.5 million people worldwide. Graphite’s platform is designed to replace defective genes with a next-generation approach that could help reduce the side effects sometimes brought on by gene editing.

There is currently no cure for sickle cell disease besides risky bone marrow transplants reserved for children with a severe form of the disease. And the disease predominantly affects people of color with one out of every 365 Black or African-American births in the US representing a case of sickle cell, according to the Centers for Disease Control and Prevention.

The company’s strategy: Graphite is beginning a phase 1/2 study in patients with sickle cell disease using a gene editing platform that can rewrite DNA, changing the way proteins are expressed. The platform stands apart from others in its class by building on CRISPR technology to make therapies that more precisely replaces sections of genetic code with donor DNA to correct a single mutation.

At a glance: Lehrer says the No. 1 goal at Graphite is bringing forward the sickle cell treatment, screening and enrolling patients at Stanford University, the University of Alabama and Washington University, and adding more sites. The first patient data is expected to read out in 2023.

In PharmaVoice’s conversation with Lehrer, he discussed how Graphite’s technology provides a uniquely precise option for targeting genetic diseases, how challenges like manufacturing are one of the biggest hurdles in gene editing, and how the company approaches the social aspects of sickle cell disease even at this very early stage of research.

PharmaVoice: How does Graphite Bio’s technology platform stand apart from the many others in the gene editing space?

Josh Lehrer: There are a lot of companies with a lot of different approaches in the gene editing space, and what we’re doing is really unique in terms of our focus. It comes from a scientific approach developed at Stanford by our main founder Matt Porteus, who’s one of the elder statesmen in the field. Going back to those early days prior to the discovery of CRISPR, the holy grail of gene editing was to actually rewrite genetic sequences to use precision repair processes in the cell to provide a template and change DNA genotypes to the normal sequence and be a definitive cure for a range of genetic diseases.

The first generation of approaches don’t do precision repair because it turns out to be a lot harder, and instead rely on the default, which is essentially cutting and breaking genes. [Porteus] stayed focused and asked how he could combine a set of tools to actually cure these diseases by returning DNA sequences to normal — so the way that we’re doing that is building on CRISPR technology. We’re focusing initially on hematopoietic stem cells because we know that these kinds of cells can be one-time lifelong cures. The traditional balance between error-prone repair and position repair has been 10 to one — and [Porteus] succeeded in inverting that to where we’re getting as high as 70% precision repair.

What are some of the fundamental challenges for companies in the gene editing space?

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