Despite deaths and trial halts, Leerink sees Juno positives

Juno took a major hit last year when a number of patients died in its experimental CAR-T test, which for months has remained under a cloud and another halt. But analysts at Leerink see reasons to be cheerful about its second next-gen blood cancer candidate.

The Rocket trial, which was testing its leading CAR-T candidate JCAR015, was put on a brief hold by the FDA in the summer of last year in blood cancer patients after a series of deaths from cerebral oedema. This was however quickly lifted a few days later, when Juno said it was another drug, fludarabine, which was used alongside its med that caused the deaths. It said it would stop using it.

But in November, the biotech put its own hold on Rocket when several more deaths were reported, again from cerebral oedema, but this time without the use of fludarabine. The drug and the company have been in limbo since then.

Related: Juno CAR-T study put on hold, again, after cerebral edemas and fatality, again

Juno said in a brief update at the annual J.P. Morgan biopharma conference last month it had a series of options for JCAR015, which include changing up the trial, or focus on its other CAR-T med, JCAR017.

Juno’s management sat down with Leerink and said that any changes to Rocket and moving forward with the test would necessitate “a high bar.” But the company was keen to highlight several differences for JCAR017 over its halted med.

This includes, Juno said, costimulatory domains (JCAR015 uses CD28 while JCAR017 utilizes 4-1BB), as well as cells (JCAR015 has T cells selected and JCAR017 has a defined cell composition with a 1:1 ratio of CD4/CD8 cells), manufacturing (with the JCAR017 process designed to deliver more naïve and quiescent cells), and the viral vector (JCAR015 employing a gamma retrovirus and JCAR017 employing a lentivirus).

Leerink said in a note to clients about the meeting: “Management emphasized that 4-1BB cells show a slower early rate of growth and last longer, and the longer persistence could lead to a more durable response in the clinic, and a defined cell product has the potential for a better therapeutic window.

“Juno also pointed to their JCAR017 data presented at ASH 2016 in diffuse large B cell lymphoma (DLBCL) as reasons for confidence, noting that their phase 1 study enrolls patients with ECOG 0,1, and 2 (vs. competitor studies enrolling just ECOG 0 and 1) with ECOG 2 patients representing a quarter to half the patient population.”

In terms of the Rocket trial, Juno’s management told the analysts that the “first phase of analysis is wrapping up and they should be in a position to talk about that relatively soon.”

The biotech, which has a market cap of around $2.6 billion and still enjoys the backing of Big Biotech Celgene, ended the day up more than 6% yesterday, but its share price, which was just shy of $24, is still half of its peak last year, before Rocket was brought back to earth. 

It had been in the leading pack to get the first-ever CAR-T med to market in the U.S., but it has now fallen behind rivals Kite Pharma and Novartis, which could both see approvals for their candidates within the next 12 months.