inno2 0 1 3 STEM CELL NETWORK vation ading through le
Stem Cell Network 2012–2013 Annual Report
Directors’ Message...... 1
Targeting New Treatments...... 4
Brain Power ...... 10
Delivering a Hard Punch with Soft Skills...... 15
Propelling Clinical Trials...... 20
Building Banks for Stem Cells...... 26
Network Community ...... 32
Financial Statements...... 37
Hot Spot Indicators Throughout this document you will find Hot Spot nodes such as this. These icons indicate a link to online media such as video, blogs, etc. To view these properly please ensure you have a browser with an active internet connection. Drew Lyall Verna Skanes Michael Rudnicki Executive Chair of the Board Scientific Director of Directors Director A message from SCN’s Board Chair, Scientific Director and Executive Director
After 12 years of innovative support and “The Stem Cell Network has investment, the Stem Cell Network is very proud of the international respect held for propelled Canada to become Canada’s stem cell research community. Through catalyzing grants and its incubation a global leader in many aspects of a strong network of stem cell scientists, SCN has propelled Canada to become a global of stem cell research, including leader in many aspects of stem cell research— including four areas highlighted in this report: drug discovery, clinical trials, drug discovery, clinical trials, stem cell banking and ethical, legal and social issues. stem cell banking and ethical,
A major reason for SCN’s success in translating legal, and social issues.” basic research to that which promises new and innovative therapies is the highly targeted and focused approach taken with the Impact and These programs demonstrate the Network’s Drug Discovery grant programs. Both of these commitment to the future of stem cell research funding channels seek out highly advanced re- in Canada, a future that will remain bright even search projects, many on the verge of clinical as the Network approaches the end of its fund- trials, and offer transitional funding to help them ing term. As a further indicator of the Network’s take the final steps from initial identification of success in moving stem cell research forward promising drugs or techniques towards clinical towards disease treatments, more than ten trials. Our article on page five features both Network-funded projects have entered the clini- Dr. Mick Bhatia and Dr. Patrick Gunning, two cal trial phase or are expected to do so within SCN researchers who used Drug Discovery the next fiscal year—including a potentially grants to rapidly move their research forward; revolutionary trial to treat degenerative brain Bhatia is about to launch a clinical trial for his disorders led by Dr. Freda Miller of Sick Kids work, while Gunning has developed a product Hospital, which is highlighted on page 11. that has industrial partners lining up to commer- Although work remains to be done before cialize. The Drug Discovery program has been these treatments are used regularly, the stem highly successful for the Network and its cell field is now maturing rapidly, and the researchers, and based on that success the Stem Cell Network’s strategic investments Network has recently increased the funding have ensured that Canada is and will continue available for these targeted projects. to be at the forefront of this dynamic discipline.
P A G E O N1 E For example, future clinical trials and treatments is ensuring Canada has a role in developing a will require a developed and cohesive infrastruc- principled stem cell banking system to serve ture of cell manufacturing facilities to supply as a role model for other countries, as well. researchers and medical professionals with reli- able and safe stem cell products. The Network As the selected accounts presented in this identified the need to align these interests and, Annual Report will attest, the Canadian stem as described on page 20, continues to incubate cell community is maturing and developing as and support CellCAN, an organization designed a world leader in the field. Work remains to be to serve as a hub for Canadian cell therapy de- done, and the role of the Network as a facilitator velopment. In addition, the Network’s recent Cell and partner for research is as important as ever. Therapy Accelerator grant program invested in But the results of the Network’s funding are the development of current good manufacturing being seen today, entering the clinical trial practice (cGMP) facilities to contain and expand process and on the way to providing novel necessary materials for present and future stem and better treatments for devastating diseases. cell trials and therapies. There are now five The pioneering legacy of Ernest McCulloch and affiliated cGMP stem cell manufacturing facilities James Till, the Canadian researchers who first in Canada, and SCN has been a major player in identified stem cells in 1961, remains strong in the initiation and growth of these facilities. Canada—and is gaining strength worldwide.
When considering the future of stem cell We are also very pleased to welcome the Inter- research, it’s important to consider future national Society of Stem Cell Research (ISSCR) stem cell researchers as well. The Network has back to Canada in June 2014 for the third time always invested heavily in training the next gen- in eight years, led by SCN’s Deputy Scientific eration of Canadian scientists, and 187 trainees Director, Dr. Janet Rossant. It is always a privi- attended at least one Network-supported lege to welcome the international community to workshop in the last fiscal year. The Network’s Canada, and we are delighted to see this coun- innovative curriculum of science-based and soft- try remains at the centre of the stem cell field. skills workshops, detailed on page 15, is ensuring that these future leaders have the technical Finally, we would like to take this opportunity knowledge necessary to conduct their research, to offer our thanks to Drew Lyall for his tremen- but also the skills necessary to communicate dous contributions to the Stem Cell Network. this research effectively to funding agencies, After 12 years of leadership, it is almost impossible policy makers and public audiences. to quantify his impact on the Network and the Canadian stem cell community, but we do wish While scientific progress is offering hugely to note Drew’s invaluable expertise that led to the promising advances for medicine, it remains prominence of the Till and McCulloch Meetings, necessary that research be done in an ethically the formation of the Cancer Stem Cell Consortium, sound and responsible manner. The Stem Cell the International Consortium of Stem Cell Net- Network is the Canadian representative in the works, the Canadian Stem Cell Foundation, and International Stem Cell Forum, and Canadian CellCAN, as well as the recognition and respect the ethicists and legal scholars—with the support Network now enjoys in international and Canadian of the Network—are prominent leaders in the circles. In short, his vision and hard work have been ISCF’s Ethics Working Party and International instrumental in the success of SCN, and we all Stem Cell Banking Initiative, both of which are wish him the best as he leaves to pursue new discussed in more detail on page 26. Their work opportunities with CIHR.
P A G E T W O “The pioneering legacy of Ernest McCulloch and James Till, the Canadian researchers who first identified stem cells in 1961, remains strong in Canada – and is gaining strength worldwide.”
P A G E T H R E E 3 Targeting New Treatments
P A G E F O U R Investing in a more rapid way of developing new drugs for devastating diseases The Stem Cell Network is taking a highly targeted and focused approach to drug discovery in order to identify novel drugs and move them through the development pipeline and into clinical use more quickly.
Picking the low-hanging fruit
The rigorous and complex nature of scientific discovery can make it a long process, a fact that can oftentimes correlate to equally long times to move a discovery from theory into practical use. However, with the wealth of scientific knowl- edge today, the Stem Cell Network’s Drug Discovery Program is working to help stem cell researchers build on what’s known to develop novel medical treatments for many diseases. “The Stem Cell Network’s Drug Discovery SCN’s Drug Discovery Program is a highly Program is rescuing science that otherwise targeted and focused funding commitment wouldn’t have progressed,” said Dr. Mick Bhatia of $2 million over five years. In that span, the of McMaster University, a Stem Cell Network Network plans to fund 20-25 distinct one-year Principal Investigator who received a Drug initiatives, pursuing specific research questions Discovery grant in 2012. “It’s very hard to get to identify compounds that affect stem cell funding for these projects. We know a lot function and demonstrate potential clinical about these compounds, but we need to know applications. Many projects funded to date a little bit more, and a lot of agencies want have focused on FDA-approved and off-patent you to know a lot more before they can offer compounds, a conscious choice which offers funding. The Stem Cell Network is very speed and cost benefits for potential clinical wisely funding a gap.” applications. Although the individual grants are relatively These grants serve as a bridge between basic and small (up to $100,000 per project), SCN’s clinical research, from the point where an assay— strategic and targeted placement of these funds a sample against which compounds are tested— means that money goes very far in helping is developed to where the optimized specific promising research move forward into clinical drug compounds are ready for a clinical trial. trials and, hopefully, novel medical treatments.
P A G E F I V E 5 “The Stem Cell Network’s Drug Discovery Program is rescuing science that otherwise wouldn’t have progressed”
– Dr. Mick Bhatia of McMaster University 69 2,600 Number of Impact and Number of compounds tested Drug Discovery grants against Dr. Mick Bhatia’s awarded since 2005 exceptional cancer stem cell assay
P A G E S I X “A screen is only as good as its assay” regimen for certain patients with acute myeloid leukemia (AML). The trial is expected to Dr. Mick Bhatia of McMaster University's Stem launch at up to three sites, including McMaster Cell and Cancer Research Institute is one of University, before the end of 2013. Thioridazine Canada’s most prominent stem cell researchers has also shown potential for treating other cancers, including breast and colon, and clinical today. His research team was recently awarded trials may move into testing against those a Drug Discovery Grant to validate the effective- ailments in the future. ness of thioridazine, an antipsychotic drug that demonstrated potential in targeting cancer Gunning for a novel cancer treatment stem cells. Even the most aggressive diseases can Before pursuing thioridazine specifically, have weaknesses, and some of the Stem Cell Dr. Bhatia tested more than 2,600 chemical Network’s researchers are identifying those compounds for their effects against a human weak spots to hone in on them and find ways cancer stem cell assay that took more than four to take advantage of them with novel treatment years to develop. Several compounds were ef- options. Dr. Patrick Gunning’s research with the fective at killing the cancer stem cells, but thiori- University of Toronto – Mississauga, which has dazine was unique in its ability to target cancer received two separate Drug Discovery Grants, stem cells specifically, while allowing normal is using this strategy to seek new treatment stem cells to continue regular functioning. options for certain brain cancers.
“For each compound there’s a concentration, In researching potential treatments for glioblas- sort of a sweet spot, to kill cancer stem cells,” toma multiforme (or GBM, an aggressive brain explained Dr. Bhatia. “At that same concentra- cancer with poor survival rates and high resist- tion, we have to assure that it doesn’t equally kill ance to currently available drug therapies), normal stem cells. So we put a further filter on Dr. Gunning focused on finding a way to inhibit the compound list, and that’s where we really a well-known cancer-promoting protein (STAT- started to reduce the number. Thioridazine can 3). His lab work discovered a particular drug- kill cancer stem cells and not have the same like molecule that tracks down STAT-3 and effect on normal stem cells, and a compound inhibits it, which ends up killing the cancerous with that kind of property is the kind we want to cells. The molecule is most effective when move forward with. From a clinical perspective, taken orally, and has shown so much promise that’s really the ideal scenario.” that multiple industrial partners are competing to collaborate with him to commercialize the With this information in hand, Dr. Bhatia is product. For his research, Dr. Gunning was currently finalizing approvals for a clinical named one of the University of Toronto’s trial using thioridazine as part of a treatment 2013 Inventors of the Year.
Video Mick Bhatia talking about how thiorizadine targets cancer stem cells without impacting healthy stem cells.
HOT SPOT
P A G E S E V E N 100,000 20 Funding available, in dollars, Number of Impact and to each Impact and Drug Drug Discovery grants to be Discovery grantee funded over next two years
Dr. Gunning’s strategic research focus on targeting There are three sub-categories of Drug Discovery and killing cancer-causing brain tumour stem cells Grants, which proceed from general identification demonstrates the type of work that benefits from of potential “hits”, to validation of specific com- SCN’s timely and results-oriented Drug Discovery pounds, and then to optimization aimed at clinical Program. And, like the work of Dr. Mick Bhatia, or commercial use. Although SCN is still funding the the chemical compound is moving towards first category of general grants, research teams are clinical trials—yet another example of how now beginning to advance through the development the Drug Discovery grants are shepherding sequence and following up on original identification promising research into the clinic. successes with validation and optimization projects. The trend reflects the efficacy of the Network’s That’s just the first half program design to carry these highly promising research ideas from their original genesis towards Since the Stem Cell Network’s Drug Discovery clinical trials and into medical treatments. Program began in 2011, the Network has funded 12 projects researching compounds that have Even though it’s still the early stages of this demonstrated potential to treat leukemia, brain innovative program, SCN has already seen very cancer, osteoporosis, spinal cord injury and other exciting research conclusions from specific projects. diseases. SCN plans to double that number of That is only expected to increase as researchers projects by 2015, leading to a grand total of up to focus in on the most promising results and push 25 Drug Discovery projects funded within a five-year those forward through product development period and a total funding envelope of $2 million. and commercialization.
P A G E E I G H T 1997 The year Canadian research and SCN PI Dr. John E. Dick first identified cancer stem cells
HOT SPOT
Video Mick Bhatia speaking about how stem cells are the key to curing cancer.
P A G E N I N E 9 Brain Power
Getting damaged brains back on track
P A G E T E N Traumatic injuries and degenerative Luck favours the prepared mind diseases of the brain are uniquely dev- Scientific discovery is no stranger to serendipity— astating conditions that have drawn the accidental discovery of something good or useful while not specifically searching for it—and significant attention from researchers, examples of it exist throughout history, from Isaac and for good reason. Stem Cell Net- Newton to Louis Pasteur. A more recent example occurred at The Hospital for Sick Children, where work Principal Investigator Dr. Freda Stem Cell Network Principal Investigator Dr. Freda Miller and her team found that metformin, a drug Miller and her team have uncovered commonly used to treat diabetes, may be able to a readily available and commonly used stimulate damaged brains to repair themselves. drug that holds great promise in In 2010, Dr. Miller’s research team was conducting stimulating stem cells in the brain to basic research on the development of neural stem cells (the stem cells that give rise to cells improve or restore brain function, and necessary in brain development and function) and discovered that one particular neural pathway the team is set to embark on a clinical was vital in their differentiation. When this path- trial this year. way is damaged, brain development is impaired, such as in the case of Rubinstein-Taybi syndrome, a developmental disorder that can cause a wide range of mental and physical disabilities.
This pathway is also associated with diabetes, and the antidiabetes drug called metformin is known to activate it. With this in mind, Dr. Miller’s team conducted further research and found that
PAGE ELEVEN metformin turned on this pathway, which When people are suffering from brain cancers, resulted in improved brain development and one conventional treatment is whole-brain spatial memory in mice as well as in vitro human radiation, which, unfortunately, has a side models. With these promising results in hand, effect of severely impairing brain development, Dr. Miller is moving forward with her colleagues especially in children. At The Hospital for Sick Drs. Donald Mabbott and Eric Bouffet to pursue Children, there are a number of young people a clinical trial at The Hospital for Sick Children who’ve undergone this treatment, but are left investigating the use of metformin in overcom- with cognitive problems that, without interven- ing brain damage in children aged 10-17 who tion, will persist for the rest of their lives. have acquired a brain injury as a consequence of their treatment for brain cancer. “The good news is that these kids survived, whereas without the treatment, they wouldn’t “This is a classic example of the importance of have,” said Dr. Miller. funding basic research,” said Dr. Miller of the findings, which she also described as serendipi- In order to offset the brain trauma, Dr. Miller is tous. “We never thought that this was going to working with Dr. Donald Mabbott, a develop- be a therapeutically-oriented study, and yet mental psychologist at The Hospital for Sick here we are, about to embark on a clinical trial.” Children, to conduct a clinical trial using met- formin to undo the damage to the developing Kick-starting brain development brains of these children.
Building on her recent research findings, “Metformin is kind of like a ‘kick,’ to make neural Dr. Freda Miller will collaborate with Drs. Donald stem cells differentiate into their progeny,” Mabbott and Eric Bouffet in leading a pending described Dr. Miller. “This clinical trial will clinical trial to help repair the brains of adoles- attempt to use metformin in these young cents that have been damaged in cancer treat- 10-17-year-old adolescents to ask if we can ment. The trial is to take place at The Hospital promote recovery, cognitively or structurally.” for Sick Children in Toronto.
120 320km/h Number of different types Speed at which signals are of primary brain tumours sent between nerve cells
HOT 18 SPOT Approximate age at Video which the brain stops Video synopsis of Dr. Miller’s research growing under normal and findings. circumstances
PAGE TWELVE “This is a classic example of the importance of funding basic research. We never thought that this was going to be a therapeutically-oriented study, and yet here we
are, about to embark on a clinical trial.” – Dr. Freda Miller
PAGE THIRTEEN On the fast track
Clinical trials are often criticized for the length With the majority of funding in place, the group of time and amount of funding required to go expects to start their clinical trial before the end from an initial discovery to actual clinical use. of 2013. While this first trial is investigating the Although that due diligence is justified in order effects of metformin on restoring brain function to protect public health, there is a safe shortcut in a very specific subset of people (namely, researchers can pursue for drug-based trials: adolescents between 10-17 who have suffered Examining the previously unknown effects of neural development problems due to whole- already-approved drugs. Dr. Freda Miller’s work brain radiation), there is realistic potential for with metformin, a commonly used anti-diabetic the treatment of numerous other degenerative drug, is a prime example. diseases of the brain. This could include other traumatic brain injuries, stroke, Alzheimer’s dis- “The advantage to a drug like metformin is that ease, and multiple sclerosis. There is much work it’s already been used chronically in our target remaining to do before these treatments are group, so we know that it’s basically safe,” widely available, but the potential is certainly Dr. Miller said. “Of course, we’re going to check there—and is very promising. that when we do our pilot trial, but nonetheless it makes a huge difference.” [Metformin] is a very safe drug that’s already used chronically in people from five years old to 105, and it might be helpful for treating
various kinds of injury or even neurodegeneration. – Dr. Freda Miller
100,000,000,000
Approximate numberof nerve cells encased in the brain
PAGE FOURTEEN Delivering a hard punch with soft skills
The Stem Cell Network is giving its young scientists Da competitive edge with an innovative suite of programs aimed at honing important soft skills.
PAGE FIFTEEN 70 129 Trainees at SCN’s Communications for SCN trainees received stipend Scientists workshop on March 20, 2013 support from SCN in 2012
HOT SPOT HOT SPOT
Blog Post Blog Post Why the pen is sometimes Social media and stem cells mightier than the pipette. time to start tweeting.
Training the next generation of scientists after the popular Dragon’s Den television series. doesn’t start and end in the lab. With tighter The Dragon panel consisted of Kevin Canning competition for academic grants and a corre- from GlaxoSmithKline, a self-described scout for sponding trend for highly qualified personnel academic-industrial collaborations; Jamie Stiff, a to seek work outside academia, it’s increasingly partner at biotech venture capital firm Genesys important that they acquire skills—such as com- Capital; and Terry Thomas, a Senior Vice-Presi- munications, writing and commercialization— dent at STEMCELL Technologies. The Dragons that will make them marketable in a knowledge were asked to judge the pitches from 12 trainee economy. The Stem Cell Network has devel- teams and were given a fictional $500,000 oped several programs and workshops to investment to award to the best pitch. For their help its trainees gain those vital skills. part, the trainees had each been tasked with homework reading and had to work within Pitching to dragons pre-assigned groups to identify their pitch prior to the workshop. Approaching industry partners to request research funding is no easy task. Often the As the HQP discovered, the biggest challenge biggest challenge lies in communicating the re- was in realizing that what’s interesting from an ac- search and its potential in a way that resonates ademic perspective might not be so from a com- with the intended audience. To help its HQP mercial point of view. The perspectives can be acquire this fundamental skill, the Stem Cell different, so the approach must be different, too. Network’s Trainee Communications Committee organized a unique and challenging commercial- “The experience was a challenging one, with the ization workshop of… dragonesque proportions. biggest obstacle facing teams was learning how to set aside academically interesting ideas that More than 70 stem cell trainees attended the wouldn’t help commercialize their technology,” March 20, 2013 workshop, which was modeled wrote Paul Krzyzanowski, who participated in
PAGE SIXTEEN 187
SCN trainees attended an SCN event in 2012
the challenge, in a post on Signals Blog The presenters showed how to target specific following the workshop. audiences—from patient groups to general public to those who may not be scientists By the end of the day, participants had learned but nevertheless have a keen interest and the importance of truly understanding their knowledge about scientific issues. Each should target audience and tailoring their messaging be considered when writing messages for to make it relevant and interesting—a lesson public consumption. This message resonated especially important when pitching to a poten- with the roughly 70 highly-qualified personnel tial partner with $500,000 (whether real or in the room. imaginary) in its back pocket. “It’s a refreshing reminder to any researcher “No one cares about your stupid science.” who wants to have a wide impact,” wrote Paul Krzyzanowski in a blog post following the event. This was one of the statements made by guest “When writing manuscripts, too often it seems presenter, John Rennie during SCN’s Communi- that there are only four people in the audience: cating to Public Audiences: Storytelling is not an editor and three referees.” Telling Stories session held on March 20 in Toronto. The session was part of a full day The workshop, which was organized by SCN’s “Communications for Scientists” workshop, Trainee Communications Committee, also pro- aimed at developing vital soft skills and expand- vided insights into audience demographics, how ing career options for young scientists. Rennie, to begin crafting messages for public consump- former editor-in-chief of Scientific American, tion right from the grant application stage, and used the statement to illustrate the challenge how to use social media not just to communi- faced by scientists in communicating to the cate research, but to learn about and connect media and general public. Overcoming that with other researchers as well. The half-day challenge involves three key steps; 1) identifying session was a follow-up to a complementary the audience, 2) identifying a problem the workshop held a year earlier that focused audience cares about, and 3) describing, in on the basics of writing in lay language to very broad terms, how research helps solve journalists and via social media. that problem.
“Our goal has been to create professional development programs that respond to these needs and deliver high quality training that has direct relevance to stem cell/regenerative medicine.” – Dr. Eva Szabo, outgoing chair of the SCN TCC
PAGE SEVENTEEN “These training opportunities will enable the HQP to succeed in career paths within regenerative medicine/stem cells spanning both academia
and industry.” – Dr. Eva Szabo, outgoing chair of the SCN TCC
these important skills. The first was a full-day Grant Review Workshop in which trainees became part of a mock review panel tasked with assessing and grading recent grant applications that were generously provided by a number of (brave) SCN investigators. The participants learned what elements constitute a successful grant application and how organize and focus their writing so they can better meet review requirements and increase their odds of receiving research grants. Academics of success The second workshop tackled journal-writing skills with a specific emphasis on how to While there are a myriad of career options produce strong journal articles, how scientific available to highly-qualified personnel (HQP) in journals work and what editors are looking for stem cell and regenerative medicine research, when they make decisions to accept or reject including those in industry, government or submissions. The session included presentations NGOs, the academic career remains one of the from journal editors and SCN investigators, who most coveted. For many young researchers, a shared their experiences and provided concrete position and lab in a respected university is the tips and examples on how to write strong titles, pinnacle of career success. But these positions abstracts and cover letters. are rare, so competitions naturally favour those who have the most impressive credentials. “Even though I helped create many of these workshops, I also found immense value in the “If you're an early career scientist, much skills that I gained, which helped me to obtain of your success is dependent on obtaining an academic placement at McMaster University research grants, writing good journal articles and to forge collaborations within academia and communicating your research to the and industry,” Szabo said. scientific community as well as the public, and yet quite often you are not taught how to Both workshops were launched at the 2012 Till & do these things,” said Dr. Eva Szabo, Assistant McCulloch Meeting as pre-conference events for Professor at McMaster University and Chair of groups of about 40 registered HQP. Due to their the SCN Trainee Communications Committee success, the two workshops are being offered a (TCC) from 2011 to 2013. second time at the 2013 Meetings to take place October 23-25 in Banff, Alberta. This prompted the SCN TCC to develop specialized workshops aimed at addressing
HOT SPOT 552 Blog Post SCN trainees and HQP who have The tooth tattoo a novel found employment upon leaving biosensor for disease detection. the Network from 2001 to 2012
PAGE EIGHTEEN Blog Post 3D patterning of blood vessels creating a fertile landscape for engineered tissues.
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Training by trainees
Logic would suggest that the people best able to identify professional development needs of early career researchers are the early career researchers themselves. That’s why the Trainee Communications Committee (TCC) plays such an important role in assisting the Network in the “development, implementation and communica- Where do they go? tion of training opportunities for SCN trainees.” Career paths of SCN Members of the TCC are selected among appli- cants from across Canada to ensure representa- Trainees after leaving tion in all Network research disciplines, including basic, clinical and translational research, the Network, 2001-2012: engineering and ethical, legal and social issues. Comprised of 10-15 members, the TCC is respon- sible for the development and organization of the majority of the Network’s professional development portfolio, including the soft skills 357 workshops, networking events and mentorship Academia programs, most of which take place at the annual Till & McCulloch Meetings. Industry 90 “Because the TCC is comprised of trainees at different stages of their careers and with differ- Government 20 ent research backgrounds, we have been able to identify a wide range of needs and areas of skill development,” said Dr. Eva Szabo, Assistant Professor at McMaster University and Chair of 85 the Trainee Communications Committee (2011- 2013). “Quite often this type of skills training is Other/unknown either not offered as part of a typical academic program, or does not adequately address the stem cell/regenerative medicine community.”
“Our goal has been to create professional devel- opment programs that respond to these needs and deliver high quality training that has direct relevance to stem cell/regenerative medicine HQP,” said Szabo. “These training opportunities will enable the HQP to succeed in career paths within regenerative medicine/stem cells spanning both academia and industry.” PAGE19 NINETEEN Propelling Clinical Trials
Building a national cell manufacturing infrastruc- ture to advance Canadian stem cell research
PAGE TWENTY Propelling Clinical Trials
PAGE TWENTY ONE 55 323,000 Number of stem cell-based Phase I/II Number of patients who have clinical trials projected to begin by been treated with cell-based 2015 in Canadian stem cell centres therapies since 1988
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Video Video Dr. Donna Johnston Allogeneic and discusses Canada’s autologous cord need for a National blood units. Public Cord Blood Bank
The Stem Cell Network is investing in the individuals rather than the patient’s own cells,” development of a cooperative, national net- explained Dr. Stewart. “This makes treatment work of cell manufacturing facilities to provide easier since we’ll have off-the-shelf products the materials necessary for stem cell-based ready to go, which is what you need in order clinical trials and therapeutic procedures. to be able to intervene within a few hours. We don’t have the luxury of taking several An off-the-shelf solution weeks to develop a product.”
Sepsis is a devastating medical condition in The team focused in on an MSC-based which the body’s immune system over-responds treatment after years of pre-clinical research to a bacterial infection. Millions of people are that identified MSCs as able to execute a diagnosed with sepsis or septic shock each year, coordinated suppression of the immune system and roughly one in four people succumb to the without interfering with its ability to clear the disease. It presents a massive challenge for initial bacterial infection. They’re also capable health care given that there is no specific of flying “under the radar” of the immune therapy that works—patients are usually system, meaning that they aren’t rejected as given antibiotics, but results vary widely. foreign and therefore avoid potential problems with graft-versus-host disease (GVHD). Responding to this huge challenge, Stem Cell Network PI Dr. Duncan Stewart and his research In order to enable this clinical trial, Dr. Stewart team are embarking on a clinical trial at the took advantage of SCN’s Cell Therapy Accelera- Ottawa Hospital Research Institute (OHRI) tor Grant program, which sought to propel to test a mesenchymal stem cell (MSC)-based pending trials into the clinic. treatment for septic shock. At the OHRI’s cell-manufacturing facility, Dr. Stewart’s team “The Stem Cell Network’s Cell Therapy collected bone marrow samples from healthy Accelerator Grant enabled us to initiate the donors, and then expanded those cells in cell manufacturing processes,” said Dr. Stewart. order to make a cell-based product that— “Health Canada needs to know every compo- importantly—is readily available as a viable nent and every step in your manufacturing treatment for septic shock. process before they’ll approve pending trials. You have to have everything worked out and “For this trial, we’ve used what are called validated beforehand, and that’s what the allogeneic cells, which are cells from other SCN grant allowed us to do.”
PAGE TWENTY TWO “We’ve put a lot of effort, time,work,and expense into developing our cell-manufacturing facilities and developing expertise in-house.”
– Dr. Duncan Stewart
100
Amount, in millions of dollars, already invested in building Canada’s five largest cGMP cell manufacturing facilities
PAGE TWENTY THREE Cell manufacturing facilities in Canada
SPOT RollUniversityHôpitalOttawa your Maisonneuve-Rosemont,Hospital cursor ofHealth Alberta,Laval, over Research Network, Québec theEdmonton map Institute, TorontoCity indicators Montréal Ottawa
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MSCs have also shown potential in treating represent the engines that will power present diseases other than septic shock, including the and future cell-based clinical trials in Canada. aforementioned GVHD as well as heart failure, Through its Cell Therapy Accelerator Program, heart attack, irritable bowel syndrome and SCN has provided funds for the development, even multiple sclerosis. The development of a standardization and sharing of best practices consistent and quality-controlled MSC product between these facilities. Although it rarely for septic shock has laid the groundwork for garners headlines, the end result of this kind potential further clinical trials and therapeutic of collaboration and knowledge sharing is a treatments for these diseases. mutually beneficial increase in efficiency that allows greater resources to be devoted to the “We’ve put a lot of effort, time, work, and important work of research and clinical trials. expense into developing our cell-manufacturing facilities and developing expertise in-house,” CellCAN: A hub for Canadian said Dr. Stewart. “We certainly have the ability cell therapy development to manufacture this product, and we can do it quite efficiently from a cost perspective, Given its rich history in the field, Canada as well.” is uniquely placed to be one of the earliest beneficiaries of stem cell research. As of fall Knowledge-sharing and collaboration 2013, more than 50 early-phase clinical trials deploying transplanted cells were expected to There are presently five current good manufac- commence within four years in Canada, pending turing practice (cGMP) cell manufacturing the alignment of the required physical, opera- facilities across Canada, in Québec, Montréal, tional and regulatory infrastructure necessary Ottawa, Toronto and Edmonton. These facilities to support them. 1,000,000 Typical cost for a 10-12 patient Phase I clinical trial
PAGE TWENTY FOUR Much has already been accomplished towards will assure accelerated trials. The end result this goal. In recent years, $80 million of federal, is the proposed establishment of CellCAN, provincial and philanthropic funds have been a new not-for-profit corporation that would invested in building new cGMP cell manufactur- act as a catalyst for the continued development ing facilities across the country. More recently, of cellular therapies. there has been complementary funding through the Centre for the Commercialization of Regen- CellCAN would offer three distinct and neces- erative Medicine to catalyze the development of sary services for researchers to conduct clinical new technologies that will support the cell man- trials: First, co-funding for Phase I/II clinical ufacturing process, as well as novel biomaterials trials, following peer review by a panel of inter- and complex tissues that could be integrated national experts; second, a national network to into cell-based products. streamline access to and use of approved cell handling and manufacturing facilities across However, while Canada appears to be well Canada; and third, flexible and nimble programs positioned, there remain profound challenges and activities to manage bottlenecks in the inhibiting the effective and timely migration clinical translation process, and promote the of these innovative treatment concepts into continued sharing of best practice. standard clinical practice, including significant fixed operating costs, a shortage of qualified SCN is continuing to foster and incubate technical personnel, and the regulatory uncer- CellCAN while seeking funding commitments, tainty typical of any new field of medicine. based on strong support for the concept from industry, the host institutions of cell processing Through a series of workshops funded by SCN, facilities, national health charities, and Health stakeholders from all sectors came to recognize Canada. If successful, this highly integral piece that goodwill and collaboration between of the cell therapy puzzle will go a long way researchers, regulators, funders and industry to ensuring the future of Canada’s stem cell can readily address these impediments and community eclipses its illustrious past. 5,000,000,000 Expected dollar value of annual worldwide sales for cell-based products by 2015
PAGE TWENTY FIVE Building Banks for Stem Cells
Stem Cell Network researchers are forging a path towards a principled public stem cell banking system in Canada and around the world
PAGE TWENTY SIX “In Canada, a national cord blood bank is particularly important because we truly value our health care system as an equitable, accessible, usable, and universal approach to health care. Collecting something from the public for the public is in harmony with the Canadian mindset.”
Dr. Bartha Knoppers, McGill University Centre of Genomics and Policy
What is a stem cell bank?
A stem cell bank is a systematically organized and searchable collection of stem cells. It’s a term often used to describe the physical collections of stem cell lines, but it’s also used to describe registries containing information about stem cell lines stored in other facilities. These banks supply high-quality cells to researchers conducting their work, and higher-quality clinical-grade lines intended for therapeutic use.
The most commonly stored stem cells today are derived from umbilical cord blood—drawn from a newborn’s umbilical cord, formerly considered medical waste, which is a rich source of blood stem cells. Stem cell banks also house embryonic stem cells, induced pluripotent stem cells, and adult stem cells (such as neural [brain] stem cells and epidermal [skin] stem cells), and those cell lines will become more commonly stored as expansion techniques continue to improve.
By centralizing stem cell lines in banks, their quality and reliability can be guaranteed. In the contemporary globalized health care landscape, however, stem cell banks stand to benefit greatly from international coordination efforts to ensure optimized best practices for storage and manipu- lation as well as common ethical and regulatory principles. That’s where McGill researchers and SCN members Dr. Bartha Knoppers and Ms. Rosario Isasi take the lead.
PAGE TWENTY SEVEN 20,000 Approximate number of cord blood transplants performed worldwide to date
Canadian leadership landscape forward, but they’re also actively
O SPOT HOT engaging stakeholders in Canada to ensure that At the McGill University Centre of Genomics and this country leads by example, as well. Working Policy, Dr. Bartha Knoppers and Ms. Rosario Isasi, with colleagues as well as with policymakers, head the International Stem Cell Forum’s Ethics Knoppers and Isasi have developed policy state- Working Party (ISCF-EWP). The group, which ments, including the aforementioned “From Knoppers chairs, is composed of stem cell re- Banking to International Governance” project, search funding agencies from around the world that have offered analysis, strategies and solu- and was launched to develop strategies “to fos- tions for moving towards translational stem cell ter the scientific and ethical integrity of research research within Canada and on the global stage. in a global context.” Their work, supported by the Stem Cell Network, has laid the foundation Building Canadian capacity for international collaboration in stem cell re- search and stem cell banking. In 2012, Knoppers In order to take advantage of the therapeutic received a Public Policy Grant from the Stem and research potential of cord blood, Canadian Video Cell Network to develop policy recommenda- Blood Services (CBS) is implementing a National SCN PI Dr. Ian Rogers tions based on the ISCF-EWP’s engagement Public Cord Blood Bank based in part on policy (Samuel Lunenfeld with national bioethics committees. recommendations from the Stem Cell Network Research Institute) that built on the research of Dr. Bartha Knop- discusses what types Over the course of nearly two decades, Knop- pers and many other SCN principal investiga- of stem cells can pers has been studying the ethical, legal and tors. The CBS national public bank began be banked. social issues surrounding biobanking in Canada collecting donations at select Ottawa hospitals and around the world. Since 2009, she and Isasi in September 2013, and will expand to the have focused in on stem cell banks. Knoppers’ Greater Toronto Area, Edmonton and latest SCN-funded project, “From Banking to Vancouver in 2014. International Governance: Fostering Innovation in Stem Cell Research,” is investigating the ethi- Stem cells are poised to greatly expand cal, legal, social and commercialization issues treatment in the Canadian health care system, surrounding stem cell banks in order to devise and cord blood represents a simple and readily international regulatory frameworks to optimize available source for them. Although there are the development of stem cell treatments. still some challenges in stem cell banking, espe- cially in terms of expanding stem cells prior to Both Knoppers and Isasi have worked with implantation, establishing a public bank gives the United Nations in establishing international Canada the infrastructure necessary to keep standards on bioethical issues. Knoppers was a up with new and improved medical procedures member of the International Bioethics Commit- for its citizens. Offering a public banking tee of the UNESCO while Isasi was very active in option, in contrast to the private banks already the development of the UN’s 2005 Declaration available, aligns well with the Canadian health on Human Cloning. They’re both frequently care system. invited to speak at international stem cell conferences, which is a reflection of their “In Canada, a national cord blood bank is international standing as global leaders. particularly important because we truly value our health care system as an equitable, accessi- Through their work, Knoppers and Isasi are ble, portable and universal approach to health pushing the international stem cell regulatory care,” said Knoppers about the National
PAGE TWENTY EIGHT Ms. Rosario Isasi, McGill University Centre of Genomics and Policy
6
Number of years before the Canadian National Cord Blood Bank reaches its target inventory of 20,000 cord blood units stored
PAGE TWENTY NINE Public Cord Blood Bank. “Collecting something Canada rolls out the welcome mat from the public for the public is in harmony with the Canadian mindset.” This autumn, the ISCF and the ISCF-EWP will be coming to Canada. Their meetings are hosted Synergy among international stem cell banks by the Stem Cell Network and organized by is especially important to Canadians given the Ms. Rosario Isasi and Dr. Bartha Knoppers in multicultural nature of our population. Blood order to demonstrate Canada’s commitment to types are largely determined by the ethnic international leadership in the sphere of stem backgrounds of patients, and finding stem cells cell banking. that will be accepted remains a major hurdle for treatment. By working to align the policies of ISCF’s Canadian meetings will take place international stem cell banks, Knoppers and alongside the 2013 Till & McCulloch Meetings Isasi are ensuring that participating countries in Banff, Alberta, and will offer ISCF members can take advantage of quantities of stem cell from 18 countries the opportunity to meet many types to ensure a match can be found for the of Canada’s stem cell researchers as a result. vast majority of patients. Since medical research has become an interna- tional venture, it’s more important than ever to This National Public Cord Blood Bank sets the encourage international collaboration and policy stage for potential future growth into banking harmonization through organizations such as other types of stem cells, as well. The Stem Cell ISCF. That fact is a driving force behind the work Network is working with leading Canadian of Knoppers and Isasi, and it’s also why SCN researchers to prepare standards and interoper- stepped up to host the upcoming meetings. able protocols that will encourage the develop- ment of a public stem cell bank to maintain not By bringing the ISCF to Banff, SCN will not only only cord blood units, but also other cellular encourage increased collaboration among the products for therapeutic uses. It’s a future international stem cell networks, but will also ex- that’s becoming more apparent by the day. pose them to the best Canadian research during the course of the Till & McCulloch Meetings. 1978 80 Transplantable stem cells are first Number of diseases that have discovered in human cord blood been treated with cord blood
HOT SPOT HOT SPOT
Video Blog Post SCN PI Dr. Ian Rogers How many facilities? (Samuel Lunenfeld Centralized vs. decentralized Research Institute) manufacturing strategies discusses the costs of for cell therapy banking cord blood.
PAGE THIRTY “It’s incredible to remember that until about ten years ago, cord blood was gener- ally considered medical waste. The understanding that the placenta and cord blood can actually contain stem cells with therapeutic potential is quite recent, and could be of significant benefit for health care.”
Dr. Bartha Knoppers, McGill University 48 Centre of Genomics and Policy
Millions of dollars required for the National Cord Blood Bank’s launch and initial operation
PAGE THIRTY ONE Network Community
PAGE THIRTY TWO Board of Directors Molecular Medicine Program, William Stanford Ottawa Health Research Institute Senior Scientist, Sprott Centre Verna Skanes (Chair) for Stem Cell Research, Ottawa Former Chair of the Board, Mick Bhatia Hospital Research Institute Canadian Blood Services Director and Senior Scientist, Stem Cell & Cancer Research Eva Szabo J. Andrew McKee (Vice-Chair) Institute, Michael DeGroote Assistant Professor, President and CEO, Juvenile Centre for Learning & Discovery, McMaster University Diabetes Research Foundation McMaster University Terry Thomas Allen Eaves Kevin Canning Vice President of President & CEO, STEMCELL Director, Research and Research and Development, Technologies, Inc. Development Alliances, STEMCELL Technologies GlaxoSmithKline Canada Jacques Galipeau Peter W. Zandstra Professor of Hematology and Timothy A. Caulfield Professor, Institute of Biomateri- Medical Oncology and Pediatrics, Professor, Health Law Institute, als and Biomedical Engineering, Emory School of Medicine University of Alberta University of Toronto
Andrew Lyall Sharon Colle International Scientific Executive Director, President and CEO, Foundation Advisory Board Stem Cell Network Fighting Blindness – Canada Michael D. Schneider (Chair) Geoff MacKay David Glass Professor, Imperial College, President and CEO, Global Head of Muscle Diseases, London Organogenesis Inc. Novartis Institutes for Biomedical Research Irwin Berstein Roderick R. McInnes Professor, Fred Hutchinson Director, Lady Davis Institute, Geoff Hicks Cancer Research Center, Jewish General Hospital Senior Investigator, Manitoba Clinical Research Division Institute of Cell Biology, Mona Nemer University of Manitoba George Daley Professor and Vice-President, Director, Stem Cell Research, University of Ottawa Judy Illes Transplantation Program, Professor of Neurology, National Children’s Hospital Boston Fabio Rossi Core for Neuroethics, University Associate Professor, Department of British Columbia Chris Mason of Medical Genetics, University of Professor, University British Columbia Tim Kieffer College London Professor, University of Michael A. Rudnicki British Columbia Lee Rubin Senior Scientist and Director, Director of Translational Medi- Regenerative Medicine Program, Michael J. Parr cine, Harvard Stem Cell Institute Ottawa Hospital Research Director, Commercial Project Institute Development, The Centre for Ethical, Legal and Social Drug Research and Development Issues (ELSI) Scientific Sue Smith Advisory Board Executive Director, Stem Cells, Janet Rossant Canadian Blood Services Chief of Research, Hospital Linda Hogle for Sick Children Professor, Department of Robert Young Medical History & Bioethics, Merck Frosst-BC Leadership Denis-Claude Roy University of Wisconsin-Madison Chair Professor, Department Director, Research Centre & of Chemistry, Simon Fraser Cellular Therapy Laboratory, Jeff Kahn University Hôpital Maisonneuve-Rosemont Professor, Johns Hopkins Berman Institute of Bioethics Research Management Cheryle Séguin Committee Assistant Professor, University Debra Matthews of Western Ontario Professor, Johns Hopkins Michael A. Rudnicki (chair) Berman Institute of Bioethics Senior Scientist & Director,
PAGE THIRTY THREE Principal Investigators Ontario Cancer Institute, Carl Hansen and Institutions Princess Margaret Hospital Keith Humphries Jim Till Judy Illes B.C. Cancer Agency James Johnson Samuel Aparicio Ottawa Hospital Research Aly Karsan Donna Hogge Institute Timothy Kieffer Peter Lansdorp Harry Atkins Brian Kwon David Courtman Francis Lynn Dalhousie University May Griffith Marc Marra Stephen Couban Caryn Ito Michael McDonald Kerry Goralski Michael Rudnicki Kelly McNagny Ivar Mendez William Stanford James Piret Christopher Sinal Duncan Stewart Fabio Rossi Bernard Thebaud Michael Underhill Hôpital Maisonneuve-Rosemont Valerie Wallace Bruce Verchere Gilbert Bernier Ron Worton Garth Warnock Jean-Sébastien Delisle Queen’s University University of Calgary Hospital for Sick Children David Lillicrap Leo Behie Peter Dirks Jeff Biernaskie James Ellis Robarts Research Institute Fiona Costello David Kaplan Arthur Brown Edna Einsiedel Freda Miller Gregory Dekaban Vincent Gabriel Janet Rossant Michael Kallos Sunnybrook and Women's Roman Krawetz Institut de recherches College Health Sciences Centre Artee Luchmann cliniques de Montréal Juan Carlos Zúñiga-Pflücker Luanne Metz Jacques Drouin Aru Narendran Université de Montréal Derrick Rancourt International Collaboration Anne Marnier Carol Schuurmans On Repair Discoveries (ICORD) Bernard Massie Samuel Weiss Wolfram Tetzlaff Denis-Claude Roy Von Wee Yong Guy Sauvageau Lawson Health Research Institute University of Manitoba David Hill Université Laval Donna Wall François Auger McGill University Frédéric Barabé University of Ottawa Jack Antel Alain Garnier Jennifer Chandler Richard Gold Lucie Germain Yann Joly Jacques Tremblay University of Regina Bartha Knoppers Amy Zarzeczny Vural Ozdemir University Health Network Lawrence Rosenberg John Dick University of Saskatchewan Norman Iscove Barbara von Tigerstrom McMaster University Armand Keating Mick Bhatia Gordon Keller University of Toronto Jon Draper Gary Levy Julie Audet John Hassell Mark Minden Benjamin Blencowe Sheila Singh Aaron Schimmer John Davies Michael Fehlings Montréal Heart Institute University of Alberta Denis Grant Hung Ly Tania Bubela Patrick Gunning Sean Caulfield Rebecca Laposa Mount Sinai Hospital (Samuel Timothy Caulfield Jason Moffat Lunenfeld Research Institute) Liz Ingram Cindi Morshead Andras Nagy Christopher McCabe Vince Tropepe Ian Rogers Devidas Menon Rachel Tyndale Jeff Wrana Derek Van der Kooy University of British Columbia Peter Zandstra Raymond Anderson Connie Eaves
PAGE THIRTY FOUR University of Waterloo University College, London Industry (29) Eric Jervis University of Cambridge Amorchem Paul Spagnuolo University of Edinburgh Astellas University of Leicester BD BioSciences University of Western Ontario University of Oxford Beckman Coulter Dean Betts University of Sheffield BioE Cheryle Seguin BioSpherix United States (23) Cellular Dynamics International York University American University Cormex Research Anthony Scime Baylor College of Medicine Deloitte Touche Case Western Reserve University Fate Therapeutics Inc. Collaborating Colorado State University GE Healthcare Institutions (58) Emory University GlaxoSmithKlineWelcome Georgia Institute of Technology Illumina Canada (19) Georgetown University Life Technologies Carleton University Harvard University Lonza Dalhousie University Indiana University Millipore McGill University Massachusetts Institute of Miltenyi Biotech McMaster University Technology Novartis Memorial University of Northwestern University Northern Therapeutics Inc. Newfoundland Stanford University Octane Inc Queen's University University of California Organogenesis Simon Fraser University University of Kansas Pfizer Canada Université de Montréal University of Maryland Reveille Université Laval University of Massachusetts Roche Diagnostics University of Alberta University of Minnesota StemCell Technologies University of British Columbia University of North Carolina Stem Cell Therapeutics University of Calgary University of Pennsylvania TAP Biosystems University of Lethbridge University of Pittsburgh Therapure BioPharma University of Manitoba University of Southern California Tissue Regeneration University of Ottawa University of Texas Therapeutics University of Saskatchewan University of Wisconsin University of Toronto Health Institutes, University of Waterloo Government Departments NGOs and Others (85) University of Western Ontario and Agencies (11) Alberta Cell Therapy Alliance Australia Federal (6) Art Gallery of Alberta Swinburn University Canada Foundation for BC Cancer Agency Foundation Innovation BrainCanada Finland Canadian Institutes of Health British Columbia Cancer Agency University of Helsinki Research Department of Foreign Brown Foundation Institute of Affairs & Intl. Trade Molecular Medicine France Genome Canada California Institute of University of Poitiers Health Canada Regenerative Medicine Intra-Agency Secretariat on Calgary FireFighters Burn Germany (2) Research Ethics Treatment Society Max-Delbrrueck Centre for Canadian Association of Molecular Medicine Provincial (5) Research Ethics Boards University of Bonn Alberta Innovates Canadian Blood Services Ministry of Economic Canadian Breast Cancer Sweden (2) Development, Innovation and Foundation Linkoping University Exports (Quebec) Canadian Stem Cell Foundation Lund University Michael Smith Foundation Cancer Stem Cell Consortium for Medical Research Centre for Commercialization Taiwan (British Columbia) of Regenerative Medicine National Chengchi University Ontario Ministry of Research Centre for Drug Research & & Innovation Development United Kingdom (8) Ontario Institute for Cancer Chelsea Art Museum Durham University Research College of Physicians and Imperial College London Surgeons of Alberta
PAGE THIRTY FIVE Creative Commons Ottawa Hospital Research Enterprise Square Gallery Institute European hESC Registry Princess Margaret Hospital Foundation Caroline-Durand Foundation Foundation Fighting Rick Hansen Man in Motion Blindness (Canada) Foundation Foundation GO Royal College of Physicians GCS Research Society and Surgeons Genetics Policy Institute Sage BioNetwork Heart & Stroke Foundation Sam's Day Fund of Canada Scottish Stem Cell Network Hôpital Enfant-Jesus Science Media Centre of Canada Hôpital Maisonneuve-Rosemont Sheridan College INSERM SickKids Foundation Institut de recherches cliniques Sir Mortimer B. Davis Jewish de Montréal General Hospital Interstate Alliance for Stem Cell Solving Kids Cancer Research Spanish National Stem Cell Bank International Consortium of Stem Cells Australia Stem Cell Networks Stem Cell Network North Rhine International Society of Stem Cell Westphalia Research St. Michael's Hospital International Stem Cell Sunnybrook and Women's Banking Initiative College Health Sciences Centre International Stem Cell Forum Terry Fox Research Institute IRICoR TheCell Research Network John P. Robarts Research The Hospital for Sick Children Institute The James Birrel Fund for Johns Hopkins Medical Centre Neuroblastoma Research Juvenile Diabetes Research Three-to-Be Foundation Toronto General and Western Lawson Health Institute Hospital Foundation Leukemia & Lymphoma Society University Health Network Let's Talk Science UK Stem Cell Bank MaRS Innovation Vancouver General Hospital Massachusetts Human Stem Cell WiCell Research Institute Bank McEwen Centre for Regenerative Medicine McMaster Museum of Art Medical Research Council Memorial Sloan Kettering Hospital Montreal Heart Institute Mount Sinai Hospital National Cell Therapy Network of Brazil National Institutes of Health New York Stem Cell Foundation Ontario Cancer Research Ethics Board Ontario College of Art &0 Design Ontario Consortium for Regeneration Inducing Therapies Oregon Biomedical Research Institute Organization for Economic Cooperation and Development
PAGE THIRTY SIX Stem Cell Network
Financial Statements March 31, 2013 and 2012
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