The cancer cell therapies available today are made by tweaking a patient’s own immune cells to better recognize and fight the disease. Orca Bio is developing what it says is the next generation of cell therapy: custom preparations made without modifying cells or genes.
Orca is already testing its technology in humans, though it has kept that research mostly under wraps. As the startup prepares to reveal its preliminary findings and ramp up its manufacturing capability, the Menlo Park, CA-based biotech announced on Wednesday the close of $192 million in financing.
The immune system is comprised of many cells that work in concert, says CEO Ivan Dimov. Some cells stimulate activity while other cells block it. But the effects of these immune cells can be dampened by the other cells around them. Orca’s therapies are allogeneic—they’re made by taking stem and immune cells from healthy donors rather than from the patients themselves, as is the case with autologous treatments. But rather than just taking those healthy cells and putting them into a patient, Orca chooses certain cells from the donor sample and combines them in specific ways. Dimov says each mixture, created from certain cell types that it has assembled in the proper ratio, forms a “custom immune army” that seeks out cancer cells and leaves healthy tissue alone.
“We’ve created a novel class of precision therapies—precise, optimal therapeutic mixtures,” he says.
Orca’s first disease targets are aggressive blood cancers that require bone marrow transplants as a treatment of last resort. These procedures offer patients a potential cure, but they also come with risks, such as rejection by the immune system.
In recent years, cell therapy has emerged as a new option for aggressive blood cancers that haven’t responded to treatment. Chimeric antigen receptor T cell therapies, or CAR-Ts, are made by engineering a patient’s own T cells, multiplying them in a lab, and then infusing them back into the patient to target and fight the cancer. The first CAR-Ts that reached the market were developed by Novartis (NYSE: NVS) and Gilead Sciences (NASDAQ: GILD). These therapies pose the risk of a potentially fatal immune system reaction.
There are other biotechs that are trying to advance CAR-T therapy by making it safer and more scalable. Some of them, like Orca, are developing allogeneic cell therapies. Two such companies, Allogene Therapeutics (NASDAQ: ALLO) and Precision Biosciences (NASDAQ: DTIL), use gene editing to eliminate parts of an immune cell that could prompt an adverse response. Those companies are testing their respective therapies in clinical trials.
Dimov says Orca’s custom therapies are meant to allow patients to avoid the complications associated with bone marrow transplants and CAR-T drugs. The descriptor “custom” needs a bit of clarification: An Orca therapy is not tailored to each patient, but rather customized to generate a particular therapeutic effect, Dimov says. If it works, the right mix not only provides the optimal treatment, it also avoids any adverse immune response. This approach offers a new way to reset and rebuild the immune system, Dimov says.
Orca has two programs in clinical trials. TRGFT-201 is a formulation of T cells and regulatory T cells (a type of cell that tamps down an immune response) that is in Phase 1/2 testing in patients with certain blood cancers. A second program, OGFT-0001, is a formulation of T cells that is in Phase 1, also in blood cancers. The new cash is expected to be enough for Orca to complete Phase 1 tests of the lead program, as well as build the startup’s manufacturing capacity.
Preliminary data from the studies have not yet been reported but Dimov says a terminally ill cancer patient who received one of the Orca therapies got well enough to leave the hospital. Anecdote aside, while full data are expected in 2022, some early findings are being prepared for peer review.
Orca traces its origins to the laboratory of Irv Weissman, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. Dimov joined Weissman’s group in 2010 as the field of cell therapy was heating up. At that time, a central obstacle to its progress was figuring out how to make cell therapy manufacturing scalable. Meanwhile, the scientific community’s understanding of immune cells continued to advance. Orca’s intellectual property covers both the cell therapy manufacturing technology, which offers the capability to sort stem and immune cells, and the therapeutic mixtures of cells. The startup spun out of Stanford in 2016 and started its first clinical trial about two years later, Dimov says.
Though cancer is Orca’s focus for now, Dimov says the company’s technology has potential applications in other diseases. Rare inherited disorders such as beta thalassemia and severe combined immunodeficiency are possible targets. Autoimmune diseases represent another opportunity. For each one, Orca would develop an appropriate mixture of immune and stem cells to treat the condition and restore immune system function, Dimov says.
Including the latest financing, Dimov says Orca has raised nearly $300 million. The new capital, a Series D round of funding, was co-led by Lightspeed Venture Partners and an unnamed investor. The other investors Orca has disclosed are 8VC, DCVC Bio, ND Capital, Abu Dhabi sovereign wealth fund Mubadala Investment Company, Kaiser Permanente, and the Illinois Municipal Retirement Fund.