Development of Promising Gene-Edited Therapies for Sickle Cell Disease Get Disrupted

Rare Daily Staff

Graphite Bio said it was discontinuing development of its experiment sickle cell disease gene-edited stem cell therapy and will lay off about half its staff following a review of its business.

Following the review of its programs, resources, and capabilities, the company said it is exploring a range of strategic alternatives.

The news came as two other companies announced disruptions to the development of their own sickle cell disease (SCD) therapies. Intellia Therapeutics in reporting its earnings, said its partner Novartis chose to discontinue the development of its autologous ex-vivo CRISPR-edited hematopoietic stem cell program targeting fetal hemoglobin for the treatment of SCD. Sangamo Therapeutics in its earnings release said it made a strategic decision to halt further investments in its zinc finger nuclease gene-edited cell therapy program for SCD beyond completion of the phase 1/2 study. It said it would redeploy resources to Fabry and TX200 programs and seek a potential collaboration partner to progress this asset to a potential phase 3 trial.

Nula-cel, formerly known as GPH101, is Graphite’s investigational, next-generation, gene-edited autologous stem cell-based therapy that is currently in development for SCD, a serious, life-threatening inherited blood disorder that affects approximately 100,000 people in the United States and millions of people around the world, making it the most prevalent, monogenic disease worldwide. Nula-cel seeks to correct the underlying mutation that causes SCD to decrease the production of sickle hemoglobin and restore the expression of adult hemoglobin, thereby potentially curing the disease.

The U.S. Food and Drug Administration granted Fast Track and Orphan Drug designations to nula-cel for the treatment of SCD.

“We believe that gene correction is the optimal way to treat sickle cell and many other genetic diseases,” said Josh Lehrer, CEO of Graphite Bio. “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.”

Graphite Bio is exploring the potential to continue nula-cel development externally. The company intends to continue research activities associated with its early-stage non-genotoxic conditioning program, with the goal of advancing toward potential development candidate(s).

As of December 31, 2022, the company had a preliminary unaudited amount of approximately $283.5 million in cash, cash equivalents and investments in marketable securities. It said it was cutting staff and taking other steps to reduce its cash burn.

Photo: Josh Lehrer, CEO of Graphite Bio