Notch Therapeutics
Making Cell Therapy Mainstream

David Main, CEO and President

Today’s Challenge for Cell Therapies

Access to a uniform and unlimited supply of cells is a critical limiting factor in the development of cell therapies to treat cancer and many other diseases. Current therapeutic white blood cell (T cell) therapies require a complex, patient-specific and time-consuming manufacturing process to modify and alter a patient’s T cells. This approach can lead to delays and variability in the cells produced, negatively impacting patient outcomes. To date, clinical-trial results for cell therapies have been widely mixed and it has been difficult for researchers to determine whether this variability in patient response has been due to the disease itself, or to the cells being administered.

Canadian biotech company, Notch Therapeutics – headquartered in Vancouver, British Columbia, with facilities in Toronto, Ontario, and Seattle, Washington – is working hard to change the game for cellular immunotherapies. The company’s proprietary technology platform enables the development of uniform, iPSC-derived T cells and other immune cells, from any source of pluripotent stem cells. These iPSC-derived cells are specifically engineered to address the underlying biology of complex disease systems.

“Our platform unlocks the ability to generate T cells and other immune cells from renewable stem cell lines, simplifying manufacturing, and giving us the ability to produce immune cells at scale, without the use of animal components or feeder cell lines,” says David Main, Notch’s CEO and President.

Induced pluripotent stem cells were first discovered in 2006 and are a type of master cell, able to produce any cell or tissue to repair the body, self-renew, and create endless copies of themselves. These cells can be cultured at scale and, in their undifferentiated state, represent a potentially limitless source of starting materials for the production of therapeutically relevant cells. Notch signaling is critical to the transformation of stem cells into mature T cells.

Drawing on more than a century of milestones in stem cell and Notch signaling research, Notch has built a platform that enables precision control of cell fate during the differentiation and expansion of stem cells in suspension bioreactors. Notch know what signals to give developing hematopoietic cells, and when to give them, to direct their development. By mimicking the niche of the human thymus, precursor cells differentiate through a series of stable intermediate populations and emerge as fully functional immune cells. Notch is then able to leverage this unprecedented control of notch signaling to achieve scale and reproducibility of complex T cell differentiation processes. The ability to deliver reliable notch signals to developing cells means Notch can take an engineering approach to solve major bottlenecks in iPSC-derived T cell manufacturing.

“Control of notch signaling is the game-changer in cell manufacturing, and is what our company is named for,” Main continues. “Our technology enables sophisticated product design in a commercially compatible stem cell manufacturing process. This is going to lead to best-in-class products, ours and our customers’.”

The Path Forward

While Notch is a young company, it is already attracting significant interest from companies and investors that view Notch’s technology platform as a path to commercialization for future generations of cell therapies. In 2019, Notch partnered with Allogene Therapeutics to apply Notch’s T cell production platform to develop CAR-targeted, iPSC-derived or natural killer (NK) therapies for hematologic cancer indications. And in 2020, the company closed an oversubscribed Series A financing.

This year, Notch is focused on delivering a clinically representative process—including equipment, procedures, materials, and cell lines—to produce batches of T cells for in vivo testing.

Notch’s internal T cell product pipeline is today focused on developing treatments for solid tumors, though the company recognizes its platform holds strong potential for non oncology indications and diseases. The company is developing intellectual property around each of the six key elements of cell therapy: the nuclease, preventing graft-versus-host disease (GVHD) and graft rejection, binder and receptor architecture, solid tumor payload, and the kill switch.

As Notch moves towards the clinic, with partners and its own product pipeline, the company is focused on balancing clinical, regulatory, and commercial needs and requirements. In spite of the pandemic, the company has seen explosive growth over the last three years and with more than 80 employees working in Canada and the United States.

“We may be early-stage, but we have revolutionary science and technology,” Main continues. “And we have a world-class team, comprising some of the most brilliant minds in preclinical science, advanced cell manufacturing, bioengineering, and systems biology. All of us, laser focused on solving the complex challenge of making cellular immunotherapies mainstream.”