Juno Therapeutics Invests Heavily in Process Development and Manufacturing

Juno Therapeutics shared some of its business strategies related to process development and manufacturing in a second-quarter earnings call on Aug. 12, 2015. According to CEO Hans Bishop, the company believes its progress in the manufacture of chimeric antigen receptor (CAR or CAR-T) T-cell products will drive the company’s success for all of its product candidates and will be especially important for JCAR015, its investigational treatment for acute lymphoblastic leukemia (ALL). FDA cleared the investigational new drug application for JCAR015 on July 30, 2015.

“We made significant investments in developing a manufacturing approach that is scalable and commercially viable,” noted Bishop during the call. “We believe the skills we’ve developed in CAR-T product characterization were an important part of our success getting [the JCAR015] IND accepted.” Bishop added, “we’re confident our capability related to process development and manufacturing is going to pay dividends across our portfolio of clinical-stage product candidates.”

After successfully scaling up the production of its CAR-T therapeutic from a lab setting to a commercial manufacturing setting, Bishop says Juno has identified parameters that help a drug’s efficacy as it relates to its pharmacodynamic and pharmacokinetic properties. Bishop said that improving cell persistence and cell expansion parameters-prior to administration to a patient-helps improve drug response rate and durability of a medication within a patient’s body. According to data on JCAR015, “By improving lymphodepletion prior to infusing CAR T-cells in patients with NHL [non-Hodgkin’s lymphoma], we showed a 100-fold increase in the peak number of CAR T-cells, a key mark of expansion, and 1000-fold increase in the number of CAR T-cells at day 28-a meaningful improvement in cell persistence.”

Juno’s Steve Harr, CFO and head of corporate development, said Juno’s “best-in-class cell activation technology” will allow for meaningful improvements in the way the company activates and grows cells in its manufacturing process. Coupled with its novel cell-selection abilities and its improvements in automation, the company says it believes its technologies will help better control its supply chain and cost of goods. Harr added that Juno’s new technologies allow the company to manufacture cells from a simple blood draw, rather than through having to perform “leukophoresis or by growing the cells after transduction of the novel gene.”

A fully human single-chain variable fragment (scFv)
Harr said immunogenicity data suggest that fully humanized antibodies work best to fight blood cancers and cancers involving solid tumors. He added that Juno’s protein engineering capabilities will be key to Juno’s success in the manufacture of cell-therapy products and will make Juno stand out among its potential competitors in the T-cell therapy space. “It is not as simple as making fully human antibodies and then utilizing the scFvs in the CAR T-cell,” Harr said, adding that its license to use Editas' technology will enhance Juno’s CRISPR gene-editing capabilities. Hy Levitsky, Juno's CSO and executive vice-president, said the company will also be using Editas' gene-editing technology for other genetic modification projects; Levitsky specifically mentioned cytokine IL-12 and 4-1BB ligand as potential future targets.

Source: Seeking Alpha (registration required)