Delivering on the Promise of New Modalities: An Interview with David Main, President & CEO, Notch Therapeutics

Innovation That Matters
David Main

As part of WuXi AppTec’s ongoing efforts to collaboratively foster new thinking and actionable approaches in advancing breakthroughs for patients, we have launched a new interview series in 2022 – “Delivering on the Promise of New Modalities” – so leading voices of R&D can share how their approaches are addressing the barriers standing in the way of breakthroughs.

Our next installment of this interview series features David Main, President & CEO of Notch Therapeutics based in Vancouver, Canada. Notch has unlocked the ability for large-quantity production of T cells and other cells from any source of stem cells to bring best-in-class cell therapies for cancer and other immune disorders. In February of 2021, Notch Therapeutics closed $85 million Series A financing to develop their pipeline of renewable stem-cell derived cancer immunotherapies.

Thank you for joining us today David. Looks like Notch’s pipeline will cover a number of therapeutic areas such as cancer and autoimmune diseases. What are your considerations behind those? 

David: Notch is primarily interested in treating cancer. Current cancer therapy challenges, which have remained unchanged for decades, include trying to improve treatment specificity and reduce toxicity. But now, significant cancer research and therapy development is focused on the immune system’s response, with cell therapies offering transformational benefits over existing standards of care. Where chemotherapies act on the cancerous tumours themselves, immunotherapies focus on harnessing immune cells to identify and destroy cancer cells directly.

Cell therapy does bring its own set of challenges. Access to a uniform and unlimited supply of cells is a critical limiting factor. Further, administering cells that are not produced by a particular patient, could introduce new toxicities such as potential rejection or triggering other immune issues.

What is your approach helping to address these challenges? How is it different from existing approaches?

David: The principles of cell therapy treatment for cancer are well established. We can take immune cells from a patient, do some engineering, and then give these cells back to the patient, to attack the cancer. However, this approach is limited to very few patients. Not all patients are well enough to donate their own immune cells. Due to a long manufacturing process, by the time we are ready to give the patient back their cells, their disease could have progressed. Even the variability in the manufacturing process means the cells may not work as expected.

Thus, Notch’s approach is to create immune cells from renewable cell sources. Our

proprietary technology platform enables the development of uniform, T cells from any source of pluripotent stem cells. These cells are now not dependant on an individual patient and can be “sitting on the shelf”, ready to treat the patient.

Any potential risks or challenges associated with this approach?

David: The benefits of cell therapy have been demonstrated scientifically but our approach is in progress and not yet proven.  We must move forward to demonstrate in clinical trials the cells we produce work to kill cancer and have an acceptable safety profile. To advance our technology, we have already attracted significant interest from companies and investors who view Notch’s technology platform as a means to maximize the benefit for future generations of cell therapies. In 2019, we 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, we closed an oversubscribed Series A financing.

This year, we are focused on delivering a clinically representative process—including equipment, procedures, materials, and cell lines—to produce batches of T cells for in vivo testing. This is a critical step in Notch’s move towards IND (Investigational New Drug) studies and ultimately clinical trials.

Look forward to your development David. Entering clinic will be an exciting milestone. Looking at the cell and gene therapy field at large, what do you see as a critical challenge to overcome?     

David: We will need to work on reducing costs. Applying new technology will help. Also because costs arise not only from how we do research, but from the amount of research required for a drug to be approved, reducing costs requires not only excellent technology, but a strong commitment from and collaboration with Regulators.

We are supportive of a strong regulatory progress. We all want to know the drugs going into our body, or that of a loved one, are safe and effective. However, with the current regulatory process, we typically see an annual increase in the body of knowledge and the addition of more regulations. It takes a strong-willed person to say it’s time to streamline the process by reviewing everything at once and then reforming the approvals process.  Dr. Richard Pazdur, Head of Oncology Center of Excellence at the FDA, is one such person. He demonstrated the commitment to revisiting potential cancer drug development and approval process and looked for ways to expedite paths to approval.

What’s your outlook for the future of cell and gene therapies? Say 2030?

David: I expect cell therapy and gene therapy will be two prominent treatment modalities. Cell and gene therapies are allowing us to harness a natural process to treat disease and to treat diseases at the gene level.  This means we can think cures, and not just treating symptoms. It means eradicating chronic diseases.

So, in 2030, I think we will have several cell therapies and a number of gene therapies approved, and these will be the mainstay approach to treating disease.

And I also believe that 100 new drugs are achievable by 2030. There is a proliferation of innovation within the industry and the progressive way we tackle treatments is accelerating every year.

Thank you David for sharing Notch’s approaches in help advancing the potential of cell and gene therapies. Best of luck in your endeavor.

David: Thank you.



David Main

President & CEO of Notch Therapeutics

David Main is 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 Mr. Main began his career as a licensed pharmacist at the Royal Columbian Hospital in New Westminster, B.C. He holds a BSc (Pharmacy) and an MBA from the University of British Columbia (UBC).

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