RARE Daily

Graphite Bio Launches with $45 Million to Advance Therapies for Genetic Diseases

September 16, 2020

Rare Daily Staff

Graphite has raised $45 million in a series A financing to advance a platform that marries gene editing with gene therapy to improve targeted DNA integration and precisely insert genetic payloads to treat a variety of severe genetic diseases.

Founding investor Versant Ventures led the financing together with Samsara BioCapital. Graphite Bio’s co-founders are pioneers in the fields of gene editing and gene therapy and the company says it has a rapidly maturing pipeline with an upcoming Investigational New Drug application and several other candidates advancing toward the clinic in the next 12-18 months.

Graphite Bio’s technology platform draws from gene-editing research from the lab of Stanford professor Matthew Porteus, an academic founder of CRISPR Therapeutics, and gene therapy expertise from Stanford professor Maria Grazia Roncarolo, who helped advance multiple gene therapy products into the clinic when she served as director of Telethon Institute for Cell and Gene Therapy at the San Raffaele Scientific Institute in Milan.

While many existing gene editing and gene therapy approaches are based on knocking out or randomly integrating genes, Graphite Bio is focused on correcting defective genes by high-efficiency site-specific integration of new genetic sequences. This technology has the potential to precisely repair a damaged portion of a gene, completely replace a malfunctioning gene while retaining normal regulatory control, or to insert a wide range of therapeutic genetic cargoes into precise regions of the genome.

In addition, Graphite says its technology has the potential to provide for durable expression while minimizing toxicity from off-target insertions.

“Our flexible, site-specific approach is extremely powerful and could be used to definitively correct the underlying causes of many severe genetic diseases, and also is applicable to broader disease areas,” said Josh Lehrer, CEO of Graphite Bio, and formerly chief medical officer at Global Blood Therapeutics where he played a key role in the clinical development and 2019 approval of the company’s Oxbryta therapy for sickle cell disease.

While CRISPR-Cas9 gene editing has transformed the biotechnology landscape due to its ability to specifically induce double-stranded DNA breaks that can disrupt genes or genetic control regions, it has been challenging to harness it for the high-efficiency insertion of new genetic cargo.

Graphite Bio’s gene editing platform includes several complementary technologies that enable targeted and permanent DNA integration at very high efficiency. The platform builds on seminal work led by Danny Dever in the laboratory of Matt Porteus at Stanford University demonstrating an increase in integration efficiency from less than 1 percent to greater than 50 percent across diverse genetic lesions in a wide range of cell types.

The efficiency improvements enable clinically meaningful levels of targeted integration for therapeutic applications. The company says its medicines therefore can replace defective genes, insert genetic cargo into specific loci and significantly limit undesirable, indiscriminate transgene expression.

“Achieving high-efficiency targeted gene integration has been a critical objective of gene editing for more than 15 years, but only now is this technologically possible,” said Jerel Davis, managing director at Versant and a Graphite Bio board member. “As the founding investor of CRISPR Therapeutics, Versant has seen first-hand the rapid evolution of the gene editing field. Our collaboration with Matt Porteus on CRISPR Therapeutics was highly productive.”

Based on progress to date, Graphite Bio expects to commence phase 1 studies of its first development candidate in early 2021. The company’s lead program specifically corrects the single nucleotide point mutation in the sickle β globin gene. In cells from patients with the disease, Graphite Bio has shown that its gene correction approach efficiently restores healthy hemoglobin protein and eliminates sickle cell hemoglobin.

Photo: Josh Lehrer, CEO of Graphite Bio

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