Manufacturing is the differentiator for CAR-T success, says Allogene

Allogene has tweaked the manufacturing process for its allogeneic CAR-T candidate ALLO-501 to produce more robust and consistent product.

Since raising $324 million (€283 million) in an initial public offering (IPO) last October, Allogene Therapeutics has announced plans to build a 118,000 square foot cell therapy manufacturing facility in Newark, California and reported its first fourth quarter financials.

In the call discussing the latter, the firm’s CEO David Chang told stakeholders that success for chimeric antigen receptor (CAR) T-cell therapies is reliant on the manufacturing process.

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“In our cell therapy experience, we know manufacturing and the strength of the technical operations team can make the difference in successful outcomes for patients or manufacturing products in time for patients.”

Chang has experience in this burgeoning field, having been one of the driving forces of bringing Yescarta (axicabtagene ciloleucel) to commercialization before selling his firm Kite Pharma to Gilead Sciences for $11.9 billion in 2017.

With Allogene’s off-the-shelf CAR-T products, manufacturing is “one of our top priorities,” he said, with “considerable time and resources” being devoted to the process.

Tweaking

As such, the firm has tweaked the manufacturing process of its ALLO-501 candidate, its CAR-T product set to be investigated in Phase I trials for lymphoma. While the molecular construct of ALLO-501 is nearly identical to lead candidate UCART19, being codeveloped with Servier, the manufacturing process is different.

He said for the manufacturing of the product there are many different aspects to consider, especially around the supply chain. “This includes raw materials, viral vectors, and any reagents that go into the manufacturing, and then there is a stepwise manufacturing process that also includes the assays in between, intermediate assays to understand what’s going on during the entire manufacturing process.”

He continued: “We haven’t really made what I would consider as a large big change, but incrementally in each of those area we have improved, and the end result is that [the] manufacturing process is more robust and consistent.”

The firm estimates that with the process it can produce enough material to treat upwards of 100 patients from each production run, ample to complete the Phase I study of 24 patients. “We believe that this yield will continue to go up as we introduce additional improvement to the manufacturing.”

In January, the firm received clearance from the US Food and Drug Administration (FDA) to commence the ALPHA trial of ALLO-501, designed to assess the safety and tolerability at increasing dose levels of ALLO-501 in the most common non-Hodgkin lymphoma (NHL) subtypes of R/R large B-cell lymphoma.