Notch Therapeutics – Maximizing the Benefit of Cell Therapies through a Proprietary T Cell-Production Platform

Cell therapy is the transplantation of human cells to replace or repair damaged tissue and/or cells. With new technologies, innovative products, and limitless imagination, many different types of cells may be used as part of a therapy or treatment for a variety of diseases and conditions. Some of the cells that may be used include hematopoietic (blood-forming) stem cells (HSC), skeletal muscle stem cells, mesenchymal stem cells, lymphocytes, dendritic cells, and pancreatic islet cells.

While the research is evolving, various cell types will be developed into treatments as novel cell therapies and studied for potential applications. Hematopoietic stem cell transplantation (also called bone marrow transplant) is the most frequently used cell therapy and is used to treat a variety of blood cancers and hematologic conditions. Potential applications of cell therapies include treating cancers, autoimmune disease, urinary problems, and infectious disease, rebuilding damaged cartilage in joints, repairing spinal cord injuries, improving a weakened immune system, and helping patients with neurological disorders.

Notch therapeutics is an early-stage biotech company, working to maximize the benefit of cell therapies through a proprietary T cell-production platform which combines sophisticated product design with commercial-compatible processes to enhance patient outcomes. Notch’s iPSC-based technology platform allows for precision control of notch signaling, which removes several critical limiting factors in the development of cell therapies, delivering the ability to design and manufacture a uniform and unlimited supply of therapeutic T cells.

Notch Signaling and T Cell Differentiation

It has been more than 100 years since scientists first described unusual fruit flies born with “notched” wings that looked as though a small bite had been taken out of them. When the causal gene of this trait was cloned in the 1980s, it was named “Notch” and hypothesized to code for a cell membrane protein involved in cell-cell interactions.

Today that the Notch genes encode a family of receptors that drive cell fate decisions by binding ligands and transmitting signals between adjacent cells. The Notch Signaling Pathway is a conserved and critical component of development for most organs and tissues, and mutations in related genes result in a wide range of phenotypes ranging from “notched” wings in fruit flies to various congenital disorders in humans. In the late 1990s, it was discovered that bone marrow cells from mice carrying mutations in the Notch1 gene could give rise to all hematopoietic lineages except T cells. Shortly thereafter, Notch Therapeutics scientific co-founder, Juan Carlos Zúñiga-Pflücker, made the seminal discovery that by artificially expressing Notch ligands (Delta-like, DL) in mouse OP9 stromal cells and co-culturing those OP9-DL cells with hematopoietic progenitor cells, one could finally generate human T cells in a dish without a thymus. Dr. Zúñiga-Pflücker has continued to advance strategies to generate T cells from stem cells.

Induced Pluripotent Stem Cells Manufacturing

Current T cell therapies require a complex, patient-specific manufacturing process. This “vein-to-vein” processing of a CAR-T therapy leads to delays and variability that negatively impact patient outcomes. iPSCs were discovered in 2006 by Shinya Yamanaka, who was later awarded the Nobel Prize for the discovery that terminally differentiated mature cells can be reprogrammed to once again have the capability to give rise to any cell of the body when given the appropriate developmental signals.

Since iPSCs can be cultured at massive scale in their undifferentiated state, they serve as a potentially limitless source of starting materials for the production of therapeutically relevant cells. The fact that iPSCs can be cultured at massive scale makes it possible to modify the genome of the cells to encode desirable attributes that will be present and active in the final differentiated cell product. For example, iPSCs can be modified to control stem cell division and differentiation, alter the tumor microenvironment, and prevent immune activity or susceptibility of the final product.To fulfill the promise of a cell therapy that can be delivered as an off-the-shelf, fully characterized medicine, Notch Therapeutics is manufacturing T cells from induced pluripotent stem cells (iPSCs).

The Visionary Leader Upfront

David Main is the President and Chief Executive Officer of Notch Therapeutics. Previously, as Chairman and CEO of Aquinox Pharmaceuticals, a company he co-founded in 2006, Mr. Main oversaw the advancement of the company’s lead product from target validation through Phase 3 clinical trials. He also led the transition of Aquinox from a private company to a NASDAQ-listed public company with approximately $300 million raised in equity capital and then completed the successful merger of Aquinox with Neoleukin Therapeutics. Prior to his leadership of Aquinox, Mr. Main served as President and CEO of INEX Pharmaceuticals and as a Vice President of QLT. He formerly served as the Chair of LifeSciences BC (formerly BC Biotech), BIOTECanada, and Accel-Rx as well as a Director of BIO.org. Mr. Main began his career as a licensed pharmacist at the Royal Columbian Hospital in New Westminster, B.C.

Mr. Main holds a BSc (Pharmacy) and an MBA from the University of British Columbia (UBC).

"Notch is working to maximize the benefits of cellular immunotherapies, with an initial focus on cancer where cell therapies offer transformational benefits over existing standards of care."