Nobel Prizewinner David Baltimore, Ph.D. has always dreamed of turning Los Angeles into a biotech hub. He tried to help it along as president of the California Institute of Technology some 20 years ago, but the idea didn’t seem to stick. Now, he’s getting another crack at it with a new cancer cell therapy company co-founded with a group of Caltech and Kite Pharma alums.
(Appia Bio)
Appia Bio launches with $52 million to develop off-the-shelf cell therapies for cancer based on hematopoietic, or blood-forming, stem cells. Its platform, dubbed ACUA, allows the programming of stem cells to become invariant natural killer T (iNKT) cells, a powerful subtype of T cell that “some folks think of as a hybrid between a natural killer (NK) cell and a T cell,” said JeenJoo “JJ” Kang, Ph.D., CEO of Appia Bio.
Though everybody has iNKT cells in their body, these cells are exceedingly rare. They make up just a fraction of white blood cells found in the peripheral blood, so it’s hard to produce them in the traditional way, which is to draw blood and expand those cells, Kang said.
“[iNKT] cells have multiple tumor cell-killing mechanisms through the natural killer and T cell pathway,” she added. “We’re going to engineer them with a CAR and we think that is positive because it can address more heterogeneous tumor antigen presentations and get around antigen loss.”
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Antigen loss or antigen escape is a process in which cancer cells stop expressing the antigen the CAR-T is designed to hunt down, such as CD19. Targeting more than one antigen could disrupt that escape mechanism and prevent relapse. It could also improve the odds of cell therapy working in solid tumors—a major pain point.
Besides solving these problems, Appia also hopes to address the barrier of access. Autologous cell therapies—that is, those made from a patient’s own cells—are complex, expensive and time-consuming to make. Some patients don’t have enough T cells or T cells of good enough quality to make those treatments.
Producing large amounts of iNKT cells from stem cells that can be stored until they’re needed could make cell therapy available to more patients and at a lower cost.
“Being able to mass-produce a cell therapy product that can be dosed to thousands of patients out of a single manufacturing run can significantly affect the economics of what the viable price point is,” Kang said. “That is another aspect that is a part of our goals: to bring that price down.”
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The ACUA technology is based on research out of the laboratory of co-founder Lili Yang, Ph.D., an associate professor at the University of California, Los Angeles who worked under Baltimore as a student and postdoc at Caltech.
Appia’s founding team also includes Pin Wang, Ph.D., of the University of Southern California and Kite alums Edmund Kim, Ph.D., and Jeff Wiezorek, M.D. Kim, who led corporate development at Kite, is Appia’s chief operating officer. Wiezorek, who led cell therapy development at Kite, is Appia’s chief medical officer.
Gilead acquired Kite in 2017, the same year its first CAR-T therapy, Yescarta, scored FDA approval. Later on, Wiezorek and Kim’s search for their next project coincided with the maturation of Yang’s technology at UCLA.
“Bringing the two together made a lot of sense, so we did that,” Baltimore said. Kang came on board from The Column Group, the VC shop she joined in 2015 after completing her Ph.D. at—you guessed it—Caltech.
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With the series A round in the bank, the team will turn to company building and advancing its lead programs in blood cancers and solid tumors, with plans to be in the clinic by the end of 2023, Kang said. 8VC led the financing, while Two Sigma Ventures, Sherpa Healthcare Partners and Freeflow Ventures also chipped in.
The company is setting up shop in Los Angeles County.
“I’m overjoyed that we’re getting space in Culver City and the people that we found really appreciate Los Angeles,” Baltimore said. “Maybe we can make it a biotech hub—we'll see—but at least we can get this company going."