Arie Belldegrun and David Chang steered Kite Pharma last year to a historic FDA approval and a $12 billion bear hug from Gilead Sciences. Now they’ve re-emerged with a new startup, Allogene, which has $300 million in backing and the rights to a CAR-T cell therapy program which is quite different from the one they brought to market with Kite.
With its cash haul, Allogene will take over U.S. development of UCART19, a cell therapy that Pfizer licensed in 2015. Pfizer has traded its rights for a 25 percent stake in Allogene. One year ago, Pfizer vice president of CAR-T research Barbra Sasu told Xconomy that products like UCART19, meant to be cheaper and easier to produce than the first wave of CAR-T, would be “the next big leap in the field.”
Now, Pfizer has handed over the reins to people with late-stage clinical CAR-T experience.
French drug firm Servier holds UCART19 rights outside the U.S. Allogene and Servier will co-sponsor Phase 2 studies in 2019, Allogene spokeswoman Christine Cassiano said, but declined to say which type of cancer will be the target.
The phase 1 studies run by Servier were for kids and adults with acute lymphoblastic leukemia (ALL), an aggressive form of the blood cancer. It’s a fairly crowded field. The first CAR-T ever approved by the FDA, tisagenlecleucel (Kymriah) from Novartis (NYSE: NVS), is for kids with ALL. Researchers at Seattle Children’s are working on next-generation CAR-T versions for pediatric ALL.
And while Yescarta, the CAR-T that Belldegrun and Chang (pictured) shepherded to approval, is for adults with non-Hodgkin lymphoma, new owner Gilead is testing it for other types of cancer including pediatric and adult ALL. (Juno Therapeutics, now owned by Celgene, failed in its first CAR-T try in adult ALL; it has said it plans to try again.)
But UCART19 is a different proposition. All CAR-T therapy is made from human T cells engineered outside the body to better recognize and kill tumors once reintroduced to a cancer patient.
UCART19, and others like it, use T cells drawn from a donor pool. If they come to market, these so-called off-the-shelf cell therapies—also called allogeneic, hence the name of Belldegrun and Chang’s new startup—are expected to be cheaper and easier to produce than the first two CAR-T products approved last year, which are autologous—that is, they require a patient to be his or her own cell donor. Compared to autologous CAR-T, relatively few allogeneic treatments have reached human studies.
One major question, not yet sufficiently answered, is whether off-the-shelf therapies like UCART19 will trigger serious or even deadly reactions such as graft-versus-host disease, in which the transplanted donor cells attack the patient’s healthy tissues. Genetic modifications to the cell are meant to prevent such attacks.
UCART19 originated with Franco-American biotech Cellectis (NASDAQ: CLLS), which owns the gene-editing technology behind the product. Cellectis cut a deal with Servier in 2014, which in turn sold U.S. rights to Pfizer.
Cellectis no longer controls UCART19 but stands to gain if it succeeds. Its shares were up 6.7 percent in midday trading Tuesday to $37.43, their highest mark since late 2015.
UCART19 first gained worldwide attention when doctors in London used it to treat two infants with ALL. The treatments worked; the children’s cancer went into remission. But the results were not part of a clinical study.
Belldegrun was Kite’s president and CEO and will be Allogene’s executive chairman. Chang was Kite’s chief medical officer and will be Allogene’s president and CEO. Belldegrun has skin in the game, too. The BellCo Capital fund, run by his wife Rebecka, is an Allogene investor, as is Belldegrun’s new $295 million venture fund Vida Ventures.
According to the agreement, San Francisco-based Allogene also gains rights to 16 preclinical CAR-T therapies that Pfizer had licensed from Cellectis in 2014, separate from the UCART19 deal. The main focus, however, is on UCART19, one of only a few allogeneic CAR-T therapies to reach human studies.
Cellectis has other CAR-T programs under its roof. Its first wholly owned treatment to reach clinical trials, UCART123, had problems last year. In a phase 1 trial, one patient died and another fell ill from an overcharged immune system, called a cytokine storm. The FDA halted the trial for two months, then lifted the hold after Cellectis agreed to lower the amount of cells per dose and make other changes.
Autologous T cell treatments can trigger similar storms; clinicians are learning how to manage them with steroids and other drugs.
Besides Pfizer, Vida Ventures, and BellCo, the investors joining Allogene’s $300 million Series A financing include TPG and the University of California Office of the Chief Investment Officer. The handoff from Pfizer to Allogene is expected to close later in the second quarter.
Frank Vinluan contributed to this report.