THE FAST TRACK FOR REGENERATIVE MEDICINE

Canada is well positioned in a highly competitive global race to scale-up advanced cell manufacturing. Can we keep up with the competition?

from penicillin to the Tesla Model 3, every great modern invention that has solved a problem plaguing the human condition has faced a significant hurdle – scaling up from the lab bench to meet demand efficiently and cost-effectively, with no loss in quality.

As breakthroughs in regenerative medicine continue to make headlines worldwide, research communities are redoubling efforts to develop sustainable technologies and processes to usher potential cell therapies into the clinic. It is perhaps one of the most technically and logistically complex quests to date in the commercialization of scientific breakthroughs. Overcoming manufacturing challenges so that cell therapies scale out, and up, reliably into affordable and efficacious treatments will unlock a potentially astronomical return on investment in terms of economic activity and improvements in human health.

The good news is that Canada, despite having relatively smaller investments from funders compared with the U.K. or the U.S., is poised to make significant headway in advanced manufacturing thanks to a unique home-grown innovation model.

“On the commercialization side, there are very few people in the world who really understand what manufacturing a cell therapy at scale may look like – nobody’s done it yet,” explains Philip Vanek PhD, general manager of GE Healthcare’s cell therapy growth strategy. “There is a lot of substantial process development work going on, new technologies that are evolving and new therapeutic indications being pursued [globally]. These things require a huge organizational ecosystem and industrialization effort, and this is where Canada stacks up in terms of the most competitive areas – understanding that industrialization and supply-chain thinking is required for these therapies to become mainstream.”

culture of collaboration

Even if the total investment in advanced manufacturing research pales in comparison to other international programs – the U.K.’s Cell and Gene Therapy Catapult program has invested over £100 million to date in R&D and commercialization efforts, with significant support for cell manufacturing – Canada maintains some advantages. Vanek credits Canada’s unique culture of collaboration and entrepreneurship for keeping the country ahead of the manufacturing curve. He highlights the work of the Stem Cell Network, the Centre for Commercialization of Regenerative Medicine (CCRM, for which he serves as a board member), the Ontario Institute for Regenerative Medicine, the BC Regenerative Medicine Cluster and others for creating an ecosystem here that encourages collaboration within and across traditional disciplines and sectors, including industry.

This supportive environment has already borne significant fruit. Last year, GE Healthcare contributed $20 million to match federal funding via CCRM to create the Centre for Advanced Therapeutic Cell Technologies (CATCT), the world’s first cell therapy development facility to adopt a collaborative model of problem-solving between the research community and industry. The facility boasts unparalleled resources in terms of bioprocess technologies and analytical systems, along with a world-class staff, that will allow researchers to develop and optimize scalable cell and gene therapy manufacturing processes quickly and effectively. In 2015, the federal government of Canada’s First Research Excellence Fund also earmarked $114 million to create Medicine by Design at the University of Toronto. Its research program is devoted solely to research and clinical translation in regenerative medicine.

taping into the talent pool

Perhaps the most significant testimonial to the value of Canada’s ecosystem is the creation of BlueRock Therapeutics, announced in December 2016. The result of a US$225 million deal between San Francisco-based venture capital firm Versant Ventures and pharmaceutical giant Bayer AG, BlueRock aims to rapidly develop cell therapies and bring them to market, with an initial focus on treatments for brain and heart ailments.

The ability to tap into the deep talent pool of Toronto’s stem cell research community topped the long list of advantages the city offered the start-up. Internationally renowned stem cell innovators Dr. Gordon Keller of the McEwen Centre for Regenerative Medicine, based at University Health Network (UHN) – North America’s largest research hospital – and Dr. Michael Laflamme of the Toronto General Hospital Research Institute have both signed on to BlueRock Therapeutics as cofounders. The new venture was also attracted to Canada thanks, in part, to efforts from the federal government to entice and retain talent in regenerative medicine, as well as CCRM’s unique plan to scale-up stem cell production through CATCT.

There may be even more good news on the way for collaborative efforts in regenerative medicine. This past May, the federal government announced a $950 million supercluster funding initiative to stimulate job creation and

We need to create an ecosystem of regenerative medicine innovation in Canada that has a critical mass.

CCRM: Delivering Economic and Health Benefits for Canadians

Regenerative medicine (RM), which aims to harness the power of stem cells, biomaterials and molecules to repair, regenerate or replace diseased cells, tissues and organs, has the promise to treat, manage and perhaps cure some of the most devastating and costly diseases in the world today.

*Here are some of the major contributions that Canadian researchers and institutions have made: Dr. John Dick, The Hospital for Sick Children and the University of Toronto, confirmed that brain tumours originate from cancer stem cells, which maintain and fuel tumour growth. 2004

Researchers led by Dr. Michael Rudnicki, Ottawa Hospital Research Institute, discovered a trigger that turns muscle stem cells into brown fat. 2013

Researchers led by Dr. Guy Sauvageau, University of Montreal, discovered a new molecule that allows for the 10-fold multiplication of stem cells in cord blood. 2015

*CANADA’S LEADERSHIP IN RM

1961

Drs. James Till & Ernest McCulloch (left, illustrated) advanced medical research across the globe with the discovery of blood stem cells. 2008

Dr. Gordon Keller, University Health Network, demonstrated cardiac specific differentiation of embryonic stem (ES) cells in culture.

THE GLOBAL MARKET

2014

Dr. Tim Kieffer, University of British Columbia, published the discovery of a protocol that can turn stem cells into insulin-producing cells in a matter of weeks.

850+ RM Companies Worldwide

Predicted RM Market Revenue Growth:

$18.9B $53.7B

2016 2021

$2.7B Gene Therapy

Global financing $5.2B (2016) 804 RM Clinical Trials

$0.5B Tissue Engineering

21%

INCREASE from 2015

$3.0B Cell Therapy CCRM’S BENEFITS TO CANADA

68% of trials moving to Phase II or III

Portfolio of Companies: Products in the Clinic or Market: New Highly Skilled Jobs:

Today 5 Years 10 Years Today 5 Years 10 Years Today 5 Years 10 Years

6 35 66 2 30 80 123 1,000 10,000

CONTACT US ccrm.ca | 416-973-3751

global growth for Canadian companies. The program encourages consortiums of large and small companies, universities and non-profits to work together to turn ideas into marketable products and services in highly innovative industries, including biosciences and advanced manufacturing. Given the potential upside from the commercialization of cell therapies in a rapidly growing global market, and our strength in Canadian-grown companies such as STEMCELL Technologies (Vancouver, BC) that enable regenerative medicine research, supercluster investment in regenerative medicine would seem a natural fit.

“The supercluster approach is perfect for regenerative medicine; we need all sectors to come together to make a difference in human health, from the government to lay the framework, entrepreneurs to build the companies, and research to drive invention and innovation. Of course, ideas and people are critical,” says Dr. Molly Shoichet, a Canada Research Chair in tissue engineering at the University of Toronto’s Donnelly Centre and an expert in science and engineering engagement. “The problems that we are trying to solve require careful, diligent and reproducible studies. Regenerative medicine requires significant investment over long periods of time and long-term vision.”

Building critical mass

Dr. Peter Zandstra, Canada Research Chair in stem cell bioengineering, director of UBC’s School of Biomedical Engineering and Michael Smith Laboratories, and co-founder and chief scientist at CCRM, stresses that despite recent advances it’s not the time for Canada to rest on its laurels. Even with significant leadership in regenerative medicine from organizations like CCRM and a robust and rapidly expanding ecosystem, opportunities to commercialize cell therapies are being aggressively pursued worldwide. That has major implications for attracting and retaining highly qualified researchers, workers, and entrepreneurs with expertise in regenerative medicine and bioengineering.

“The next step is really to start building anchor companies in the cellular therapeutics space,” he says. “We don’t yet have one, but some of the opportunities we have are already in play in partnership with CCRM spinoffs such as ExCellThera, and associated companies; and that’s really exciting.”

Further industrialization will expand the ecosystem to the point where successful companies have the potential to compete for the best trainees, creating a sustainable knowledge base so that talent can move around in the same jurisdiction, he adds.

“We’re not quite there yet. We are at the exciting stage where there are just not enough people to fill the opportunities we are creating and seeing. We need to create an ecosystem of regenerative medicine innovation in Canada that has a critical mass. Training people for jobs, whether they are undergrads that work in the industry directly or graduates that lead it, is a really a great opportunity for Canada. Certainly, we are much better off than we were 10 years ago, and CCRM has really driven that.”

CCRM’s President and CEO, Michael May PhD, notes that Canada’s ability to punch above its weight in regenerative medicine is the result of a step-wise, strategic plan to build an industry by leveraging scientific excellence, key networks, infrastructure and academic institutions. The next critical step, he says, is to engage Canadian risk capital to achieve critical mass.

“It will be risk capital that will truly scale and drive the industry here, so we need to execute and build successes to drive investment,” he stated. “That’s how we are truly going to exploit our chances to win. We also need investors to be Canadian, so the companies they create are ‘sticky’ here.”

“When you tie that investor piece to CCRM’s focus on manufacturing, you get a doublebarrelled tool for stickiness. That’s been the heart of CCRM’s approach.”

While we’re not celebrating in the winner’s circle just yet, all signs suggest it’s a strategy that has shifted Canada into the fast lane toward producing cell therapies at scale — and on the road to a win-win for the health of Canadians and our economy.

To see this story online visit www.biotechnologyfocus.ca/the-fasttrack-for-regenerative-medicine/