If blood cancer treatments Kymriah and Yescarta were chapter one for cell therapy, Allogene Therapeutics’ pipeline of off-the-shelf CAR-T therapies is chapter two. But the company, founded by the executives who created Yescarta, is getting a head start on chapter three: Allogene is teaming up with Notch Therapeutics to create cancer treatments made from stem cells rather than mature T cells.
Though treatments made from induced pluripotent stem cells may take longer to get into the clinic than Allogene’s current pipeline—which is based on donor T cells—they will be the “next chapter” in cell therapy, said David Chang, M.D., Ph.D., Allogene’s president and CEO.
“It became something I really did not want to pass up,” Chang told FierceBiotech. “... Given our position in allogeneic cell therapy, I felt that Allogene had to step into this field and start shaping it rather than just being a bystander and watching the field evolve from the sidelines.”
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The partners will use Notch’s Engineered Thymic Niche (ETN) technology to develop T-cell or natural killer cell treatments for three kinds of blood cancers: multiple myeloma, leukemia and non-Hodgkin lymphoma. The platform works by mimicking the environment of the human thymus, where stem cells go to mature into T cells, Ulrik Nielsen, Ph.D., executive chairman of Notch, told FierceBiotech.
Allogene is handing over $10 million upfront and picking up a 25% stake in Notch but is promising much more in the backloaded deal, according to a statement. Notch could net another $7.25 million in research payments and $4 million per target if it meets certain preclinical milestones. After that, the amounts skyrocket, with Allogene promising up to $283 million per target and cell type. The partners did not disclose how many targets or cell types this could total.
Notch’s technology comes out of the labs of Juan-Carlos Zúñiga-Pflücker, Ph.D., at Sunnybrook Research Institute in Toronto and Peter Zandstra, Ph.D., at the University of Toronto. It can help surmount some of the pain points in the manufacturing of T-cell treatments, namely scalability and consistency.
Unlike treatments made from donor cells or a patient’s own cells, the therapies Allogene and Notch want to make would come from a renewable source of genetically identical cells. This would make cell therapy available for many more people.
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“Each of those T cells you pull out of the blood from a donor, or even a patient if it’s an autologous cell therapy, each of those will be a little bit different,” Nielsen said. “Maybe they have different T-cell receptors, maybe they’re at different sets of differentiation. There are lots of genetic differences between them as well. We don’t have that when we start with a clonal [stem cell] population.”
Nielsen estimates that 50 to 100 patients could be treated using a heterogeneous population of donor T cells. With a bank of uniform stem cells, one batch could treat hundreds or even thousands of patients, he said.
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Notch will get right to work creating the stem cell lines and manufacturing T cells for the Allogene collaboration, but the Canadian company wants to develop its own internal programs. It is expanding the company both in Toronto and Vancouver and hopes to move its own programs “aggressively toward patient use,” Nielsen said.
It hasn’t disclosed which disease areas it’s interested in just yet, but Zandstra, Notch’s chief scientific officer and co-founder, may have left a clue: “This work with Allogene may also pave the way for additional off-the-shelf cell therapeutics that are custom-designed to treat other immunity-related diseases such as infectious diseases, autoimmune diseases and aging,” he said in the statement.