Graphite Bio gives up on lead sickle cell program, halves staff in wake of safety scare

It took a little more than a month for Graphite Bio to conclude that there’s no way out of the safety issues unearthed in the first clinical trial of its first gene editing program. Not now.

Having paused a Phase I/II trial in the beginning of 2023 after the first patient to receive the product developed a serious side effect, Graphite says it’s shelving the program, nulabeglogene autogedtemcel, and kicking off a process to explore strategic alternatives — something that often results in a sale, reverse merger or even wind-down these days.

As part of that reorg, Graphite is laying off about 50% of its employees. Jane Grogan, a Genentech vet who had jumped from ArsenalBio to become Graphite’s chief scientific officer, and chief business officer Philip Gutry are both leaving by the second quarter.

It’s a major disappointment for an approach that the biotech once said could lead to a “definitive cure.”

Graphite had 114 full-time employees as of Sept. 30, 2022, and counted a little more than $283 million in cash, cash equivalents and investments in marketable securities at the end of 2022.

Josh Lehrer

“We believe that gene correction is the optimal way to treat sickle cell and many other genetic diseases,” said CEO Josh Lehrer in a statement. “However, after an extensive assessment of the nula-cel program, we made the difficult decision to discontinue nula-cel development based on the time and resources needed to resume the CEDAR study and the evolving treatment landscape for sickle cell disease.”

In the statement, Graphite said it will continue research on non-genotoxic conditioning regimens before transplants, but didn’t specify whether it plans to pursue other programs listed in the pipeline, including other uses of its gene editing platform.

Founded with scientific insight drawn from Matthew Porteus, Maria Grazia Roncarolo and Daniel Dever out of Stanford, Graphite set out to apply a next-gen gene editing tool to stem cell transplants. To make nula-cel, scientists took stem cells from patients and edited them to correct the genetic mutation causing red blood cells to form a sickle shape.

But the first patient in its Phase I/II, who was dosed in August, experienced pancytopenia, a condition marked by low blood cell counts over a long period of time. As a result, the patient needed “ongoing transfusion and growth factor support,” Graphite revealed in January.

Analysts wrote at the time that finding exactly what caused the issue could be a long and uncertain process.

In the meantime, companies leveraging earlier gene editing technologies are leaping ahead. Vertex and CRISPR say they’re on track to complete a BLA filing for their ex vivo gene-edited therapy, which works similarly to nula-cel, as does bluebird bio with lovo-cel. Earlier players include Beam Therapeutics.

Others are concentrating efforts on more traditional methods. Lehrer himself was an executive at Global Blood Therapeutics, the biotech that got a small molecule drug approved for sickle cell before getting acquired by Pfizer for $5.4 billion.

therapeutics
stem cells
crispr
gene editing
biotech