Graphite Bio has filed to raise up to $100 million in an IPO. The money will support the development of gene editing drugs for sickle cell disease, X-linked severe combined immunodeficiency syndrome (XSCID) and Gaucher disease.

South San Francisco-based Graphite debuted with $45 million and a plan to cure sickle cell in 2020 before going on to reel in a further $150 million just months later. Now, Graphite is working to keep up the pace of its whirlwind arrival on the biotech scene by pulling in still more money from public investors. 

The IPO filing comes in the run-up to the enrollment of the first sickle cell patient in a phase 1/2 trial of Graphite’s lead candidate GPH101. Graphite designed GPH101 to correct the genetic mutation responsible for sickle cell disease and thereby create a pool of hematopoietic stem and progenitor cells capable of producing functionally normal red blood cells expressing normal adult hemoglobin.

Graphite, which expects to have initial proof-of-concept data by the end of next year, has generated preclinical evidence of the effectiveness of its approach, for example in a mouse study that linked the gene correction therapy to an increase in red blood cell life span from two days to 19 days. 

However, the novelty of Graphite’s approach means it faces many risks and uncertainties, as it sets out in the IPO filing. The submission identifies off-target cuts as a “significant potential risk,” noting they “could lead to disruption of a gene or a genetic regulatory sequence at an unintended site in the DNA.” Graphite said delayed adverse events could happen because of the potential for the persistent biological activity of the genetic material.

The biotech is putting together a financial foundation that could enable it to cope with any bumps in the road. Graphite ended March with $177 million in cash. Once the size of the IPO is finalized, that figure could swell toward $300 million or beyond.

Graphite will use the money to advance GPH101 alongside several other candidates. Gene replacement therapy GPH201 is in IND-enabling studies in XSCID, a disease in which multiple mutations in a single gene prevent normal immune system function. Graphite expects to file an IND by mid-2023.

The XSCID candidate is being followed down the pipeline by GPH301, a therapy designed to treat Gaucher by inserting a functional copy of the gene for glucocerebrosidase into the chromosomal location of the CCR5 gene. Graphite is aiming to file an IND for GPH301 by mid-2023.

Graphite’s areas of focus puts it up against a raft of other gene editing and gene therapy biotechs such as Beam Therapeutics, bluebird bio, CRISPR Therapeutics, Editas Medicine, Intellia Therapeutics and Sangamo Therapeutics.

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