Juno amps up its CAR-T tech in drive toward a pivotal test

Juno Therapeutics, one of the most closely watched biotechs in the hot CAR-T space, turned up at ASCO on Monday to tell the industry that it has made some significant upgrades to its therapeutic design that should help it move closer to commercialization with a product that can be efficiently manufactured by the fast-growing company.

Juno's Mark Frohlich

A Phase I/II study of JCAR014 used a new process to maximize cell expansion and persistence, and registered some dramatic results for B-cell cancers, particularly improving its outlook for non-Hodgkin lymphoma (NHL). And while JCAR014 is being sidelined now, the biotech says that it gained some important translational insights that can now be used in advancing JCAR017 toward a multicenter study set to begin soon.

Juno ($JUNO) already established its proof-of-concept data in the field, offering some jaw-dropping early results from a technology that reengineers T cells into a swarm of attackers that can fight cancers. What it's looking for now is the data it will need to stay in the lead, with new ways to amp up the efficacy, control a deadly side effect and make a personalized cancer therapy that will be relatively easy to manufacture. Juno also wants to move quickly beyond this first set of leukemia patients and target a wider number of cancers, including solid tumors.

This particular study was done in 52 patients with acute lymphoblastic leukemia, NHL and chronic lymphoblastic leukemia. Using a new regimen for lymphodepleting chemotherapy, the investigators at the Fred Hutch said that the therapy achieved improved peak level and duration of persistence of both CD4+ and CD8+ CAR-T cells. Remissions were tracked in 21 of 23 B-cell ALL patients (91%); complete or partial remissions in NHL in 12 of 19 evaluable patients (63%); with two of the 5 CLL patients achieving remission.

"Early indications that these improved kinetic properties are translating to improved clinical activity with complete or partial responses in 6/7 (86%) of evaluable NHL patients," Juno said in a release.

Significantly, there were 11 serious cases of cytokine release syndrome, with two patients dying after receiving a 2X107 cells/kg dose. There were no deaths in the 2x106 dose group, or lower.

In an interview with FierceBiotech, Juno EVP of development and portfolio strategy Mark Frohlich and CFO Steve Harr say they'll be taking what they learned from this study and applying it to a study for JCAR017, a drug that Harr adds has all the characteristics of a therapy that they can manufacture more readily than JCAR014. And this Phase II study now in the works could be sufficient to satisfy regulators as a registration study, says Frohlich.

Juno has benefited enormously from the frenzy of investor interest in CAR-T and related TCRs over the past 18 months. The company seemingly came out of nowhere, and went from a startup to a successful IPO in a year's time--an unheard of speed in an industry that's been known to require a lot of time to develop new classes of treatments.

But time is a luxury that Juno doesn't have. It has to move lead programs straight ahead into late-stage studies while working out manufacturing challenges and learning how to swiftly drive fresh adaptations using new technologies that are also being picked up by rivals like Novartis ($NVS), Kite ($KITE), Adaptimmune ($ADAP), Cellectis ($CLLS), Intrexon ($XON) and more. That sense of urgency and innovation was in the air just days ago when Juno struck a deal to use the CRISPR/Cas9 gene editing tools that Editas has been developing.

- here's the release

Special Reports: The 25 most influential people in biopharma in 2015 - Hans Bishop - Juno Therapeutics | FierceBiotech's 2014 Fierce 15 - Juno Therapeutics