With the acquisition of Neogene Therapeutics this week and a CAR-T now in phase 1 courtesy of a Chinese deal, AstraZeneca hopes to add the first volumes to a planned “library” of off-the-shelf cell therapies.
The U.K.-headquartered Big Pharma may be a relative latecomer to the cell therapy game, but it's making up for lost time. Last week, the company announced the acquisition of Neogene, which sees T-cell receptor therapies (TCR-Ts) as the best way to tackle solid tumors—a key indication for many cell therapy-focused biotechs.
In an interview with Fierce Biotech, AstraZeneca’s executive vice president of oncology R&D Susan Galbraith, Ph.D., was keen to position the acquisition as part of a broader cell therapy strategy that also encompasses traditional and next-generation CAR-Ts.
"If you're going to bring cell therapy effectively to a large number of patients with solid tumors, then you really need this TCR-based capability to complement the cell surface-targeted therapies," Galbraith says.
While AstraZeneca did not join Big Pharma contemporaries Johnson & Johnson, Novartis and Bristol Myers Squibb in the first generation of CAR-T developers, Galbraith explains that the company now has its own autologous version in the clinic courtesy of an agreement with China-based Cellular Biomedicine Group. The therapy, which is directed at a cell surface receptor called oncofetal antigen glypican 3, or GPC3, entered phase 1 trials in May for hepatocellular cancer.
The asset in question is a so-called “armored” CAR-T. In essence, this means the T-cell has received additional engineering to “help it survive and create signaling and activation in a more immunosuppressive environment,” she says.
Galbraith points to emerging evidence this year that CAR-Ts trained on targets like the antigen claudin-6 could be effective against solid tumors but says there are a couple hurdles to overcome: “One is increasing the range of cancers that can be targeted by adding the T cell receptors to the spectrum of cell surface receptors. Secondly, we need to learn about the other things that we need to do with these T cells to enable them to overcome the microenvironment in solid tumors, which is more immunosuppressive.”
This is where Neogene comes in, as incorporating TCR technology “increases the spectrum of cancers that can then be targeted,” Galbraith says. “You probably need to put that together with armoring and maybe in combination with some of our bispecific immune therapies to help overcome the potential for exhaustion.”
Can we expect to see more CAR-T trials from AstraZeneca in the coming months? “We've been building our internal cell therapy capability over the last three years,” Galbraith says. “So you can imagine that we have plans for several different agents to come into the clinic over the next few years.”
The aim of these various cell therapy efforts is to create what AstraZeneca described last week as a “library of off-the-shelf patient-ready therapies already developed from the cells of healthy donors.” The vision for the library is a screening system to match patients with the most relevant cell therapy quicker, leading to better outcomes.
These T cell receptor-based therapies need to be matched to each patient's HLA haplotype, according to Galbraith.
“So that means that you've got a big screening effort to identify a relatively small number of patients that might be suitable for an individual therapy. If you knew what the patient's haplotype was, and you knew what mutation they had ahead of time, you could potentially design something from the library," she said.
This week’s acquisition, as well as the agreement with Cellular Biomedicine, suggests AstraZeneca is happy to search for other authors to contribute books to the Big Pharma’s growing library. So should we expect more M&A announcements in the near future?
“We're always looking on the outside for technologies and capabilities that can be complementary to what we already have,” Galbraith says. “The science is really exciting in the space and it's evolving.”