The technology being developed at Graphite is designed to target a specific gene and repair it in living cells with high accuracy and efficacy. The company’s lead candidate aims to repair the genetic mutation responsible for sickle cell disease.
Given the recent funding — with primary investments coming from Versant Ventures and Samsara BioCapital — and the progress made during development so far, Graphite plans to launch a Phase 1 clinical trial for sickle cell patients in early 2021.
“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,” Josh Lehrer, MD, CEO of Graphite Bio, said in a press release. “[W]e look forward to progressing our novel medicines into the clinic for patients with high unmet needs.”
CRISPR/Cas9, which is short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9, is a technique that scientists can use to directly and specifically edit the DNA of an organism.
The machinery of the CRISPR/Cas9 system is derived from proteins naturally found in bacteria, which allow the bacteria to defend against viral infection by eliminating unwanted viral DNA from the bacterial genome.
The adaptation of this DNA detection system to animal cells has been widely used in laboratory research because of its high level of specificity in identifying and replacing sequences of DNA.
However, one drawback to CRISPR is that the efficiency of integrating new DNA into cells is generally less than 1%, meaning that fewer than 1 out of every 100 cells contains the desired DNA inserted into its genome.
This is believed to be because it relies on an error-prone DNA repair mechanism to glue the piece of DNA into the cell’s genome.
To improve CRISPR efficiency, the team at Graphite Bio paired the technique with AAVs, non-harmful viruses, to deliver a template molecule that enables cells to used a more accurate DNA repair mechanism to insert that new piece of DNA. According to the company, the efficiency of this technique is greater than 50%.
“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, PhD, managing director at Versant and a board member of Graphite. “As the founding investor of CRISPR Therapeutics, Versant has seen first-hand the rapid evolution of the gene editing field.”
With its lead therapeutic candidate, Graphite is developing this technique for the targeted repair of the beta globin component of the HBB gene, which is mutated in people with sickle cell.
The company intends to expand this technology to treat other diseases, with plans to file an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) and launch additional clinical studies in the next 12 to 18 months.
“It is gratifying to see our work on new gene editing approaches being translated into novel therapies,” said Matthew Porteus, MD, PhD, a professor at Stanford University and a scientific founder of Graphite Bio. “I’m very excited to be working with Versant again on a start-up and I look forward to collaborating with Samsara and the Graphite Bio team to bring a new generation of genetic treatments to patients.”
The $45 million in new funding was raised during a Series A financing round, the first round of investments fielded by a start-up company that typically already has initial seed money and an established business plan.
Graphite Bio reported having recruited a team that includes researchers who previously worked at organizations like CRISPR Therapeutics and San Raffaele Telethon Institute for Cell and Gene Therapy.