Astellas Pharma vowed to grow into a global leader in cell therapy and other forms of regenerative medicine when it promoted Kenji Yasukawa, PhD, to CEO in 2018.
Today, Yasukawa will lead Astellas in celebrating one of its most tangible examples of that commitment, as the Japanese pharma giant formally opened its $120 million expanded Astellas Institute for Regenerative Medicine (AIRM) facility in Westborough, MA.
About 180 employees will be based at the 262,000-square-foot facility. Manufacturing employees will account for about half of AIRM’s workforce in Westborough; the other half includes R&D and clinical staffers.
“One of the focuses of the new facility is to reinforce our manufacturing capability and capacity,” AIRM President Yoshitsugu (Yoshi) Shitaka, PhD, told GEN.
To that end, the new AIRM facility houses seven GMP clean rooms compliant with global requirements from regulators that include the FDA, the European Medicines Agency, and Japan’s Pharmaceuticals and Medical Devices Agency. AIRM’s former 60,000-square-foot site, 9 miles northeast of Westborough in Marlborough, MA, housed three GMP clean rooms.
The Westborough site will cover manufacturing of clinical trial material or CTM and initial commercialization of cell therapies. Astellas’ cell therapy pipeline is led by ASP7317, a human retinal pigment epithelial (RPE) cell therapy candidate derived from pluripotent human stem cells and developed in-house.
ASP7317 is under study in a three-stage Phase I/II trial (NCT03178149) assessing the cell therapy candidate in adults ages 50+ who have been diagnosed with dry age-related macular degeneration (AMD).
“We have the capacity to not only pursue the current RPE program, but also to expand into some of the new areas that we’re very excited about,” said Robert Lanza, MD, a pioneer in induced pluripotent stem cell (iPSC) research, who is now AIRM Global Head/Chief Scientific Officer. “We have the ability now to expand and also pursue possibly downstream various other ocular programs.”
Those programs, Lanza said, include cell therapies based on photoreceptors, retinal ganglion cells and corneal endothelial cells.
Looking Beyond Ophthalmology
But Astellas’ cell therapy efforts are progressing beyond ophthalmology.
The company’s other pipeline cell therapy candidate is ASP7517, the lead program among those based on an artificial adjuvant vector cell (aAVC) formulation loaded with Wilms Tumor 1 (WT1), an antigen highly expressed in patients with acute myeloid leukemia (AML) and other cancers. aAVC formulations contain modified human cells to which glycolipids and cancer antigens are loaded.
Astellas agreed to license aAVC for oncology last year from Japan’s RIKEN research institute, through an agreement whose value was not disclosed. Astellas reasons that aAVC could effectively attack cancer cells by activating both innate immunity and adaptive immunity: The glycolipids activate innate immunity via natural killer T cells, while the cancer antigens induce antigen-specific T cells designed to activate adaptive immunity.
Long-lasting anti-tumor effects are also expected from inducing antigen-specific memory T cells, activations that depend on the full activation of dendritic cells in the body.
ASP7517 is under study in a Phase I/II open label trial (NCT04079296) designed to evaluate its safety, tolerability and efficacy in patients with relapsed/refractory AML and relapsed/refractory higher risk myelodysplastic syndrome. The first patient was treated with ASP7517 in October 2019.
“We also are pursuing programs to treat heart, kidney, lung, and vascular diseases, as well as autoimmune and neuroinflammatory disorders,” Lanza said. “One of our lead pipeline candidates is to treat Crohn’s disease. But we’re also interested in stroke, just to name a few. So this facility allows us to do all this work in one location.”
The first of those candidates could reach IND status and enter the clinic “in the coming one to two years,” Shitaka said.
Astellas expanded into cell therapy in 2016 when it acquired Ocata Therapeutics for $379 million. Lanza was Chief Scientific Officer of Ocata (formerly Advanced Cell Technology), which focused on developing regenerative medicine and cell therapy technologies for eye diseases, both iPSC and human embryonic stem cell (hESC). Ocata’s “regenerative ophthalmology” approach identified cell types that were compromised or lost due to disease, then replaced those missing cells with the same cell generated from a stem cell source.
Lanza cloned the world’s first early-stage human embryos in 2001, and 13 years later was first to successfully generate stem cells from adults using therapeutic cloning. When Astellas bought Ocata, it hired Lanza to lead its global regenerative medicine efforts.
Astellas’ efforts to build up cell therapy included additional acquisitions. Astellas bought Seattle-based Universal Cells in 2018, inheriting its technology for creating allogeneic or “off-the-shelf” cell therapies based on producing pluripotent stem cells with lower immunological rejection.
In December 2019, Astellas completed its up-to-$665 million acquisition of Xyphos, a South San Francisco company whose deal intended to bolster the buyer’s cancer immunotherapy pipeline with Xyphos’ Advanced Cellular Control through Engineered Ligands (ACCEL) technology platform. ACCEL is designed to enable a patient’s own natural immune cells to be redirected by bispecific antibodies or to be re-programmed to express a highly flexible and versatile chimeric antigen receptor (CAR).
A month later, Astellas-owned Universal Cells agreed to partner with Adaptimmune Therapeutics to co-develop and co-commercialize up to three stem-cell derived allogeneic T-cell therapies for cancer, applying both Astellas’ Universal Donor Cell Platform and Adaptimmune’s stem-cell derived allogeneic T-cell platform. The collaboration could generate more than $897.5 million for Adaptimmune and up to $552.5 million for Astellas.
“Universal Cells and Xyphos have developed unique ways to engineer cells. So in addition to the primary cells that we generate, we also are very interested in engineering these primary cells into next-generation stem cells, to avoid immune rejection but also to improve the stem cell functionality to responsiveness and persistence beyond what people thought was possible,” Lanza said. “They are very synergistic, and definitely add to the ability of us to generate the next generation of cells.”
Lanza and Yasukawa were among dignitaries that led a virtual dedication of the new AIRM facility. Joining them and AIRM leaders were Massachusetts Lt. Governor Karyn Polito; Robert Langer, ScD, David H. Koch Institute Professor at MIT; and Robert Coughlin, President & CEO of the Massachusetts Biotechnology Council (MassBio), the Bay State’s life sciences industry group.
“We’ve been around a while, so there’s been a lot of work in the research and discovery phase, figuring out how to turn the pluripotent stem cells into all the various vital differentiated cell types,” Lanza said. “Now comes the really exciting part, which is the chance to basically revolutionize medicine, and to actually bring them into the clinic where they can actually help people.”