CRISPR lauds easy scale-out of autologous sickle cell therapy

The autologous nature of its gene-edited stem cell candidate CTX001 means scaling manufacturing from clinical to commercial will be relatively easy, says CRISPR Therapeutics.

Codeveloped with Vertex Pharmaceuticals, CRISPR Therapeutics’ CTX001 is an autologous CRISPR/Cas9 gene-edited hematopoietic stem cell therapy targeting patients suffering from β-thalassemia and sickle cell disease.

Production of the candidate involves collecting a patient’s own blood stem cells via mobilization and apheresis and editing them with CRISPR/Cas9 to increase fetal hemoglobin (HbF) expression. When the edited cells are returned to the patient, they are expected to generate red blood cells that have increased levels of HbF, which may reduce or eliminate patients’ symptoms.

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The firm recently presented positive Phase I/II data for the autologous candidate and now has an eye on scaling-up production as it progresses through the clinic.

“We don’t believe we will need to make any major modifications to the manufacturing process that we started with, to take it into commercialization, and that’s a huge benefit,” Lawrence Klein, CRISPR’s COO said at the 20th Annual Needham Virtual Healthcare Conference this week. “And that’s just by virtue of the fact that our initial manufacturing process led to the type of efficacy that we saw, and we purpose built that process to enable commercial scale.”

Therefore, to increase production the firm needs to add more suites: scaling-out, rather then scaling-up.

“You can basically just clone those suites, and the more suites you have the more throughput you have,” he told delegates. “It’s not like if you’re moving from a 10-liter reactor to a 10,000-liter reactor [when] things change in terms of the biochemistry of the process.”

To augment production – “adding people and facility and instrumentation” – the firm uses undisclosed contract manufacturing organizations (CMO).

“When we started the trial, we had one,” said Klein. “We’ve added CMOs since that point, different facilities and we intend to continue doing that to enable broader scale in different geographies.

“The CMOs that we’ve chosen, they’re scalable. And you can see the major CMO’s are making heavy investments in this space of gene and cell therapy. And so, we think we’ll be able to scale that capacity as we move forward into commercialization.”

CRISPR Therapeutics is also building a cell therapy manufacturing facility in Framingham, Massachusetts being designed to provide GMP manufacturing in compliance with US Food and Drug Administration (FDA) and European Medicines Agency (EMA) regulations and guidelines.