Graphite Bio abandons sickle cell therapy, half of staff

Josh Lehrer, GraphiteBio

Graphite Bio abandons sickle cell therapy, half of staff

Published: Feb 23, 2023

By Tristan Manalac


A once highly touted gene therapy for sickle cell disease (SCD) has come to an end, at least internally, as Graphite Bio announced Thursday it is discontinuing the development of nulabeglogene autogedtemcel (nula-cel), its lead asset.

Simultaneously, the Bay Area biotech is launching a corporate restructuring program that will shave off about 50% of its workforce, among other initiatives, “to reduce cash burn,” according to the announcement. As of year-end 2022, Graphite had around $283.5 million in cash, cash equivalents and marketable securities.

Nula-cel is an autologous hematopoietic stem cell therapeutic leveraging gene editing designed to precisely correct the mutation in the beta-globin gene that causes SCD. It seeks to suppress the production of sickle hemoglobin while also restoring levels of healthy adult hemoglobin.

Graphite was studying nula-cel in the Phase I/II, open-label CEDAR trial, which enrolled 15 participants to evaluate the candidate’s safety, engraftment success, gene correction rate and effect on total hemoglobin levels. The company dosed its first patient for CEDAR in August 2022.

A few months later, however, Graphite voluntarily put the trial on hold after a patient experienced prolonged periods of low blood cell counts, a condition called pancytopenia. While this alone did not meet the threshold to pause the study, the company deemed the serious and unexpected adverse event likely related to the study drug.

While the patient in question achieved neutrophil engraftment as defined by CEDAR, and has shown no signs of myelodysplasia, the episode of pancytopenia required ongoing transfusion and growth factor support.

Graphite had been working on risk factor mitigation strategies, including changing its manufacturing process for nula-cel into a commercial process, Stephanie Yao, VP, communications and investor relations, told BioSpace at the time. Yao said Graphite would “assess whether these modifications could address important drug product attributes.”

In Thursday’s announcement, however, Josh Lehrer, CEO, said it was no longer a sound business decision to continue nula-cel’s development, given “the time and resources needed to resume the CEDAR study and the evolving treatment landscape” for SCD.

The company still believes in its gene-correction approach to treat SCD and will explore potential external development for nula-cel.

In line with the strategic realignment, Graphite will continue research activities for its early-stage non-genotoxic conditioning program for hematopoietic stem cell transplantation, which aims to make the company’s gene therapies accessible to a wider range of disease and patients.

Graphite has yet to detail plans for its remaining assets in development, including its beta-thalassemia gene replacement therapy GPH-102 and its targeted gene insertion candidate for alpha-1 antitrypsin deficiency.

Source: BioSpace