- Pfizer Inc. on Tuesday inked a deal to hand rights to a slate of "universal" CAR-T cancer immunotherapy candidates to Allogene Therapeutics Inc., taking a 25% stake in the newly-launched biotech.
- Allogene, which will be led by former Kite Pharma executives, will take the reins in developing an early-stage candidate for leukemia called UCART19 and 16 preclinical assets. Pfizer had originally licensed the so-called "off-the-shelf" programs from Cellectis SA and Servier.
- The biotech will continue Pfizer's partnership with Cellectis, which had lined up nearly $3 billion in clinical and commercial milestones across 15 targets under the 2014 deal. UCART19 was separately licensed from Servier.
Allogene, a brand-new company, has leaders who are no strangers to the CAR-T game. The company is co-founded and led by former executives of Kite Pharma: Arie Belldegrun, who will serve as executive chairman, and David Chang, who will serve as president and CEO. They were instrumental in developing what became Yescarta (axicabtagene ciloleucel) at Kite and successfully negotiated the sale of the biotech to Gilead Sciences Inc. for $11.9 billion.
Allogene's lead asset UCART19 (once a Servier/Pfizer asset), an allogeneic CAR-T therapy currently in Phase 1 development for the treatment of acute lymphoblastic leukemia (ALL), is of primary interest. The candidate has somewhat of a spotty past — although it helped some patients achieve remission, efficacy appeared to wane over time and one patient passed away due to transplant complications.
While much evidence has shown CAR-T based therapies can work for blood cancers — as supported by recent FDA approvals for Novartis AG's Kymriah (tisagenlecleucel) and Gilead's Yescarta — these therapies are highly personalized, with cells from donors being manipulated ex vivo on a case-by-case basis.
Universal CAR-T therapies, therefore, are an attractive alternative to pursue, holding out the promise of easier commercialization without as much high-touch manufacturing and handling of patient cells.
Other potential benefits have attracted interest as well. Cells are taken from healthy donors in allogeneic treatment, while in autologous CAR-T therapy cells may potentially be exhausted from prior treatment attempts such as chemotherapy.
Plus, vein-to-vein turnaround time for autologous therapies is currently about three weeks, whereas allogeneic treatment could be available faster — potentially helping the technology's commercial potential.
But the risk of manufacturing failure may be high, with some experts saying that universal therapies could be more complicated to manufacture and may have a long way to go before they are safe. Potential risk factors also include concerns over immunogenicity triggered by the donor cells.
There is also some evidence that autologous CAR-T therapies demonstrate better cell persistence, or their ability to promote long-term anti-tumor effects after initial adoptive T cell transfer.
Cellectis itself has been on the hunt to develop these universal treatments for some time now, and has come up with some novel constructs for CAR-T it thinks could help set its CAR-T apart from other designs.
Alexandre Juillerat, a scientist at Cellectis, said in 2016 that UCART123 is the first IND filing for a gene-edited CAR-T cell product in the U.S. It is worth mentioning that Allogene will harness older gene-editing technologies — TALEN technology, not the currently more popular CRISPR — to edit their T cell therapies. Cellectis has CRISPR on deck, too, although Allogene only mentions TALEN in conjunction with UCART19.
Chang already has identified that certain cell culture conditions must be maintained to get the optimal type of cells to use for CAR-T. While still in his role at Kite, Chang said the company was looking into optimizing the manufacture of T cells so that it could identify and expand the more naïve set of cells (those with a younger phenotype). He said at the time that optimization of the cell expansion phase could lead to better cell persistence and in turn, better antitumor activity.
Chang has also suggested using different cytokines during the cell manufacturing process or using inhibitors of certain pathways to keep the cells from differentiating from their young state.