Creating a diverse group of future scientists

Students in CIRM’s Bridges program showing posters of their work

If you have read the headlines lately, you’ll know that the COVID-19 pandemic is having a huge impact on the shipping industry. Container vessels are forced to sit out at anchor for a week or more because there just aren’t enough dock workers to unload the boats. It’s a simple rule of economics, you can have all the demand you want but if you don’t have the people to help deliver on the supply side, you are in trouble.

The same is true in regenerative medicine. The field is expanding rapidly and that’s creating a rising demand for skilled workers to help keep up. That doesn’t just mean scientists, but also technicians and other skilled individuals who can ensure that our ability to manufacture and deliver these new therapies is not slowed down.

That’s one of the reasons why CIRM has been a big supporter of training programs ever since we were created by the voters of California when they approved Proposition 71. And now we are kick-starting those programs again to ensure the field has all the talented workers it needs.

Last week the CIRM Board approved 18 programs, investing more than $86 million, as part of the Agency’s Research Training Grants program. The goal of the program is to create a diverse group of scientists with the knowledge and skill to lead effective stem cell research programs.

The awards provide up to $5 million per institution, for a maximum of 20 institutions, over five years, to support the training of predoctoral graduate students, postdoctoral trainees, and/or clinical trainees.

This is a revival of an earlier Research Training program that ran from 2006-2016 and trained 940 “CIRM Scholars” including:

• 321 PhD students
• 453 Postdocs
• 166 MDs

These grants went to academic institutions from UC Davis in Sacramento to UC San Diego down south and everywhere in-between. A 2013 survey of the students found that most went on to careers in the industry.

  • 56% continued to further training
  • 14% advanced to an academic research faculty position
  • 10.5% advanced to a biotech/industry position
  • 12% advanced to a non-research position such as teaching, medical practice, or foundation/government work

The Research Training Grants go to:

AWARDINSTITUTIONTITLEAMOUNT
EDUC4-12751Cedars-SinaiCIRM Training Program in Translational Regenerative Medicine    $4,999,333
EDUC4-12752UC RiversideTRANSCEND – Training Program to Advance Interdisciplinary Stem Cell Research, Education, and Workforce Diversity    $4,993,115
EDUC4-12753UC Los AngelesUCLA Training Program in Stem Cell Biology    $5 million
EDUC4-12756University of Southern CaliforniaTraining Program Bridging Stem Cell Research with Clinical Applications in Regenerative Medicine    $5 million
EDUC4-12759UC Santa CruzCIRM Training Program in Systems Biology of Stem Cells    $4,913,271
EDUC4-12766Gladstone Inst.CIRM Regenerative Medicine Research Training Program    $5 million
EDUC4-12772City of HopeResearch Training Program in Stem Cell Biology and Regenerative Medicine    $4,860,989
EDUC4-12782StanfordCIRM Scholar Training Program    $4,974,073
EDUC4-12790UC BerkeleyTraining the Next Generation of Biologists and Engineers for Regenerative Medicine    $4,954,238
EDUC4-12792UC DavisCIRM Cell and Gene Therapy Training Program 2.0    $4,966,300
EDUC4-12802Children’s Hospital of Los AngelesCIRM Training Program for Stem Cell and Regenerative Medicine Research    $4,999,500
EDUC4-12804UC San DiegoInterdisciplinary Stem Cell Training Grant at UCSD III    $4,992,446
EDUC4-12811ScrippsTraining Scholars in Regenerative Medicine and Stem Cell Research    $4,931,353
EDUC4-12812UC San FranciscoScholars Research Training Program in Regenerative Medicine, Gene Therapy, and Stem Cell Research    $5 million
EDUC4-12813Sanford BurnhamA Multidisciplinary Stem Cell Training Program at Sanford Burnham Prebys Institute, A Critical Component of the La Jolla Mesa Educational Network    $4,915,671  
EDUC4-12821UC Santa BarbaraCIRM Training Program in Stem Cell Biology and Engineering    $1,924,497
EDUC4-12822UC IrvineCIRM Scholars Comprehensive Research Training Program  $5 million
EDUC4-12837Lundquist Institute for Biomedical InnovationStem Cell Training Program at the Lundquist Institute    $4,999,999

These are not the only awards we make to support training the next generation of scientists. We also have our SPARK and Bridges to Stem Cell Research programs. The SPARK awards are for high school students, and the Bridges program for graduate or Master’s level students.

CIRM funds clinical trials targeting heart disease, stroke and childhood brain tumors

Gary Steinberg (Jonathan Sprague)

Heart disease and stroke are two of the leading causes of death and disability and for people who have experienced either their treatment options are very limited. Current therapies focus on dealing with the immediate impact of the attack, but there is nothing to deal with the longer-term impact. The CIRM Board hopes to change that by funding promising work for both conditions.

Dr. Gary Steinberg and his team at Stanford were awarded almost $12 million to conduct a clinical trial to test a therapy for motor disabilities caused by chronic ischemic stroke.  While “clot busting” therapies can treat strokes in their acute phase, immediately after they occur, these treatments can only be given within a few hours of the initial injury.  There are no approved therapies to treat chronic stroke, the disabilities that remain in the months and years after the initial brain attack.

Dr. Steinberg will use embryonic stem cells that have been turned into neural stem cells (NSCs), a kind of stem cell that can form different cell types found in the brain.  In a surgical procedure, the team will inject the NSCs directly into the brains of chronic stroke patients.  While the ultimate goal of the therapy is to restore loss of movement in patients, this is just the first step in clinical trials for the therapy.  This first-in-human trial will evaluate the therapy for safety and feasibility and look for signs that it is helping patients.

Another Stanford researcher, Dr. Crystal Mackall, was also awarded almost $12 million to conduct a clinical trial to test a treatment for children and young adults with glioma, a devastating, aggressive brain tumor that occurs primarily in children and young adults and originates in the brain.  Such tumors are uniformly fatal and are the leading cause of childhood brain tumor-related death. Radiation therapy is a current treatment option, but it only extends survival by a few months.

Dr. Crystal Mackall and her team will modify a patient’s own T cells, an immune system cell that can destroy foreign or abnormal cells.  The T cells will be modified with a protein called chimeric antigen receptor (CAR), which will give the newly created CAR-T cells the ability to identify and destroy the brain tumor cells.  The CAR-T cells will be re-introduced back into patients and the therapy will be evaluated for safety and efficacy.

Joseph Wu Stanford

Stanford made it three in a row with the award of almost $7 million to Dr. Joe Wu to test a therapy for left-sided heart failure resulting from a heart attack.  The major issue with this disease is that after a large number of heart muscle cells are killed or damaged by a heart attack, the adult heart has little ability to repair or replace these cells.  Thus, rather than being able to replenish its supply of muscle cells, the heart forms a scar that can ultimately cause it to fail.  

Dr. Wu will use human embryonic stem cells (hESCs) to generate cardiomyocytes (CM), a type of cell that makes up the heart muscle.  The newly created hESC-CMs will then be administered to patients at the site of the heart muscle damage in a first-in-human trial.  This initial trial will evaluate the safety and feasibility of the therapy, and the effect upon heart function will also be examined.  The ultimate aim of this approach is to improve heart function for patients suffering from heart failure.

“We are pleased to add these clinical trials to CIRM’s portfolio,” says Maria T. Millan, M.D., President and CEO of CIRM.  “Because of the reauthorization of CIRM under Proposition 14, we have now directly funded 75 clinical trials.  The three grants approved bring forward regenerative medicine clinical trials for brain tumors, stroke, and heart failure, debilitating and fatal conditions where there are currently no definitive therapies or cures.”

Physicians and patient advocates on the front lines of the fight for a more equitable health system

Over the last year there has been increasing awareness of the inequalities in the American healthcare system. At every level there is evidence of bias, discrimination and unequal access to the best care. Sometimes unequal access to any care. That is, hopefully, changing but only if the new awareness is matched with action.

At the recent World Stem Cell Summit CIRM helped pull together a panel of physicians and patient advocates who have been leading the charge for change for years. The panel was called ‘Addressing Disparities, Promoting Equity and Inclusion in Clinical Research.’

The panelists include:

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Ysabel Duron – Founder of The Latino Cancer Institute & CIRM Board member
Adrienne Shapiro – sickle cell disease patient advocate, Founder of Axis Advocacy – Sickle Cell Disease support and advocacy group
Dr. Leah Ke‘ala‘aumoe Dowsett – Clinical geneticist, serves on hospital DEI committee, Board member Association of Native Hawaiian Physicians
Dr. Nathan Chomilo – Co-Founder, Minnesota Doctors for Health Equity and head of the Minnesota COVID Vaccine Equity Program

The conversation they had was informative, illuminating and fascinating. But it didn’t sugar coat where we are, and the hard work ahead of us to get to where we need to be.

Enjoy the event, with apologies for the inept cameo appearance by me at the beginning of the video. Technology clearly isn’t my forte.

A word from our Chair, several in fact

In 2005, the New Oxford American Dictionary named “podcast” its word of the year. At the time a podcast was something many had heard of but not that many actually tuned in to. My how times have changed. Now there are some two million podcasts to chose from, at least according to the New York Times, and who am I to question them.

Yesterday, in the same New York Times, TV writer Margaret Lyons, wrote about how the pandemic helped turn her from TV to podcasts: “Much in the way I grew to prefer an old-fashioned phone call to a video chat, podcasts, not television, became my go-to medium in quarantine. With their shorter lead times and intimate production values, they felt more immediate and more relevant than ever before.”

I mention this because an old colleague of ours at CIRM, Neil Littman, has just launched his own podcast and the first guest on it was Jonathan Thomas, Chair of the CIRM Board. Their conversation ranged from CIRM’s past to the future of the regenerative field as a whole, with a few interesting diversions along the way. It’s fun listening. And as Margaret Lyons said it might be more immediate and more relevant than ever before.

UCSF Nursing Professor Joins CIRM Board

Elena Flowers, PhD, RN, newest member of the CIRM Board: Photo courtesy UCSF

Elena Flowers, PhD, RN, an associate professor of physiological nursing at the University of California, San Francisco (UCSF) is joining the Board of the California Institute for Regenerative Medicine (CIRM), the state’s Stem Cell Agency.

Dr. Flowers was appointed to the Board by State Controller Betty T. Yee who said: “Ms. Flowers’ experience and express commitment to equitable health outcomes for California’s diverse communities will bring a valued perspective to the work ahead.”

Dr. Flowers is a member of the UCSF Institute for Human Genetics and the International Society of Nurses in Genetics. As a researcher her work focuses on genomics involving precision medicine and risk factors for cardiovascular health and type 2 diabetes. She is also a teacher and has lectured internationally on issues such as topics from racial disparities in Type 2 Diabetes to the implications of genomic technologies for the nursing workforce.

CIRM Board Chair, Jonathan Thomas, PhD, JD, welcomed the appointment: “Dr. Flowers brings a wealth of experience and expertise to our Board and, as a nurse, she will bring a different perspective to the work we do and help us in trying to better address the needs of underserved communities.” 

“I am honored to have the opportunity to serve the citizens of California in this capacity,” says Dr. Flowers. “CIRM has ambitious goals, seeking to improve upon common limitations of public research agencies by its commitment to delivering meaningful findings and ultimately treatments for patients as rapidly as possible. I’m particularly committed to improving inclusion and access to these treatments across the entire diverse California population.”

Dr. Flowers got her undergraduate degree at UC Davis and then served as a research assistant at Zuckerberg San Francisco General Hospital. She then went on to get her MS and Doctor of Philosophy degrees at the UCSF School of Nursing.

In her spare time she has no spare time because she is the mother of two young daughters.

Month of CIRM: Reviewing Review

Dr. Gil Sambrano, Vice President Portfolio & Review

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. Today we take a look at our Review team.

Many people who have to drive every day don’t really think about what’s going on under the hood of their car. As long as the engine works and gets them from A to B, they’re happy. I think the same is true about CIRM’s Review team. Many people don’t really think about all the moving parts that go into reviewing a promising new stem cell therapy.

But that’s a shame, because they are really missing out on watching a truly impressive engine at work.

Just consider the simple fact that since CIRM started about 4,000 companies, groups and individuals have applied to us for funding. Just take a moment to consider that number. Four thousand. Then consider that at no time have there been more than 5 people working in the review team. That’s right. Just 5 people. And more recently there have been substantially fewer. That’s a lot of projects and not a lot of people to review them. So how do they do it? Easy. They’re brilliant.

First, as applications come in they are scrutinized to make sure they meet specific eligibility requirements; do they involve stem cells, is the application complete, is it the right stage of research, is the budget they are proposing appropriate for the work they want to do etc. If they pass that initial appraisal, they then move on to the second round, the Grants Working Group or GWG.

The GWG consists of independent scientific experts from all over the US, all over the world in fact. However, none are from California because we want to ensure there are no possible conflicts of interest. When I say experts, I do mean experts. These are among the top in their field and are highly sought after to do reviews with the National Institutes of Health etc.

Mark Noble, PhD, the Director of the Stem Cell and Regenerative Medicine Institute at the University of Rochester, is a long-time member of the GWG. He says it’s a unique group of people:

“It’s a wonderful scientific education because you come to these meetings and someone is putting in a grant on diabetes and someone’s putting in a  grant on repairing the damage to the heart or spinal cord injury or they have a device that will allow you to transplant cells better and there are people  in the room that are able to talk knowledgeably about each of these areas and understand how this plays into medicine and how it might work in terms of actual financial development and how it might work in the corporate sphere and how it fits in to unmet medical needs . I don’t know of any comparable review panels like this that have such a broad remit and bring together such a breadth of expertise which means that every review panel you come to you are getting a scientific education on all these different areas, which is great.”

The GWG reviews the projects for scientific merit: does the proposal seem plausible, does the team proposing it have the experience and expertise to do the work etc. The reviewers put in a lot of work ahead of time, not just reviewing the application, but looking at previous studies to see if the new application has evidence to support what this team hope to do, to compare it to other efforts in the same field. There are disagreements, but also a huge amount of respect for each other.

Once the GWG makes its recommendations on which projects to fund and which ones not to, the applications move to the CIRM Board, which has the final say on all funding decisions. The Board is given detailed summaries of each project, along with the recommendations of the GWG and our own CIRM Review team. But the Board is not told the identity of any of the applicants, those are kept secret to avoid even the appearance of any conflict of interest.

The Board is not required to follow the recommendations of the GWG, though they usually do. But the Board is also able to fund projects that the GWG didn’t place in the top tier of applications. They have done this on several occasions, often when the application targeted a disease or disorder that wasn’t currently part of the agency’s portfolio.

So that’s how Review works. The team, led by Dr. Gil Sambrano, does extraordinary work with little fanfare or fuss. But without them CIRM would be a far less effective agency.

The passage of Proposition 14 means we now have a chance to resume full funding of research, which means our Review team is going to be busier than ever. They have already started making changes to the application requirements. To help let researchers know what those changes are we are holding a Zoom webinar tomorrow, Thursday, at noon PST. If you would like to watch you can find it on our YouTube channel. And if you have questions you would like to ask send them to info@cirm.ca.gov

A Month of CIRM: Where we’ve been, where we’re going

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. We kick off this event with a letter from our the Chair of our Board, Jonathan Thomas.

When voters approved Proposition 14 last November, they gave the Stem Cell Agency a new lease on life and a chance to finish the work we began with the approval of Proposition 71 in 2004. It’s a great honor and privilege. It’s also a great responsibility. But I think looking back at what we have achieved over the last 16 years shows we are well positioned to seize the moment and take CIRM and regenerative medicine to the next level and beyond.

When we started, we were told that if we managed to get one project into a clinical trial by the time our money ran out we would have done a good job. As of this moment we have 68 clinical trials that we have funded plus another 31 projects in clinical trials where we helped fund crucial early stage research. That inexorable march to therapies and cures will resume when we take up our first round of Clinical applications under Prop 14 in March.

But while clinical stage projects are the end game, where we see if therapies really work and are safe in people, there’s so much more that we have achieved since we were created. We have invested $900 million in  basic research, creating a pipeline of the most promising stem cell research programs, as well as investing heavily on so-called “translational” projects, which move projects from basic science to where they’re ready to apply to the Food and Drug Administration (FDA) to begin clinical trials.

We have funded more than 1,000 projects, with each one giving us valuable information to help advance the science. Our funding has helped attract some of the best stem cell scientists in the world to California and, because we only fund research in California, it has persuaded many companies to either move here or open offices here to be eligible for our support. We have helped create the Alpha Stem Cell Clinics, a network of leading medical centers around the state that have the experience and expertise to deliver stem cell therapies to patients. All of those have made California a global center in the field.

That result is producing big benefits for the state. An independent Economic Impact Analysis reported that by the end of 2018 we had already helped generate an extra $10.7 billion in new sales revenue and taxes for California, hundreds of millions more in federal taxes and created more than 56,000 new jobs.

As if that wasn’t enough, we have also:

  • Helped develop the largest iPSC research bank in the world.
  • Created the CIRM Center of Excellence in Stem Cell Genomics to accelerate fundamental understanding of human biology and disease mechanisms.
  • Helped fund the construction of 12 world class stem cell institutes throughout the state.
  • Reached a unique partnership with the National Heart, Lung and Blood Institutes to find a cure for sickle cell disease.
  • Used our support for stem cell research to leverage an additional $12 billion in private funding for the field.
  • Enrolled more than 2700 patients in CIRM funded clinical trials

In many ways our work is just beginning. We have laid the groundwork, helped enable an extraordinary community of researchers and dramatically accelerated the field. Now we want to get those therapies (and many more) over the finish line and get them approved by the FDA so they can become available to many more people around the state, the country and the world.

We also know that we have to make these therapies available to all people, regardless of their background and ability to pay. We have to ensure that underserved communities, who were often left out of research in the past, are an integral part of this work and are included in every aspect of that research, particularly clinical trials. That’s why we now require anyone applying to us for funding to commit to engaging with underserved communities and to have a written plan to show how they are going to do that.

Over the coming month, you will hear more about some of the remarkable things we have managed to achieve so far and get a better sense of what we hope to do in the future. We know there will be challenges ahead and that not everything we do or support will work. But we also know that with the team we have built at CIRM, the brilliant research community in California and the passion and drive of the patient advocate community we will live up to the responsibility the people of California placed in us when they approved Proposition 14.

A model for success

Dr. Maria Millan, CIRM’s President & CEO

Funding models are rarely talked about in excited tones.  It’s normally relegated to the dry tomes of academia. But in CIRM’s case, the funding model we have created is not just fundamental to our success in advancing regenerative medicine in California, it’s also proving to be a model that many other agencies are looking at to see if they can replicate it.

A recent article in the journal Cell & Gene Therapy Insights looks at what the CIRM model does and how it has achieved something rather extraordinary.

Full disclosure. I might be a tad biased here as the article was written by my boss, Dr. Maria Millan, and two of my colleagues, Dr. Sohel Talib and Dr. Shyam Patel.

I won’t go into huge detail here (you can get that by reading the article itself) But the article “highlights 3 elements of CIRM’s funding model that have enabled California academic researchers and companies to de-risk development of novel regenerative medicine therapies and attract biopharma industry support.”

Those three elements are:

1. Ensuring that funding mechanisms bridge the entire translational “Valley of Death”

2. Constantly optimizing funding models to meet the needs of a rapidly evolving industry

3. Championing the portfolio and proactively engaging potential industry partners

As an example of the first, they point to our Disease Team awards. These were four-year investments that gave researchers with promising projects the time, support and funds they needed to not only develop a therapy, but also move it out of academia into a company and into patients.  Many of these projects had struggled to get outside investment until CIRM stepped forward. One example they offer is this one.

“CIRM Disease Team award funding also enabled Dr. Irving Weissman and the Stanford University team to discover, develop and obtain first-in-human clinical data for the innovative anti-CD47 antibody immunotherapy approach to cancer. The spin-out, Forty Seven, Inc., then leveraged CIRM funding as well as venture and public market financing to progress clinical development of the lead candidate until its acquisition by Gilead Sciences in April 2020 for $4.9B.”

But as the field evolved it became clear CIRM’s funding model had to evolve too, to better meet the needs of a rapidly advancing industry. So, in 2015 we changed the way we worked. For example, with clinical trial stage projects we reduced the average time from application to funding from 22 months to 120 days. In addition to that applications for new clinical stage projects were able to be submitted year-round instead of only once or twice a year as in the past.

We also created hard and fast milestones for all programs to reach. If they met their milestone funding continued. If they didn’t, funding stopped. And we required clinical trial stage projects, and those for earlier stage for-profit companies, to put up money of their own. We wanted to ensure they had “skin in the game” and were as committed to the success of their project as we were.

Finally, to champion the portfolio we created our Industry Alliance Program. It’s a kind of dating program for the researchers CIRM funds and companies looking to invest in promising projects. Industry partners get a chance to look at our portfolio and pick out projects they think are interesting. We then make the introductions and see if we can make a match.

And we have.

“To date, the IAP has also formally enrolled 8 partners with demonstrated commitment to cell and gene therapy development. The enrolled IAP partners represent companies both small and large, multi-national venture firms and innovative accelerators.

Over the past 18 months, the IAP program has enabled over 50 one-on-one partnership interactions across CIRM’s portfolio from discovery stage pluripotent stem cell therapies to clinical stage engineered HSC therapies.”

As the field continues to mature there are new problems emerging, such as the need to create greater manufacturing capacity to meet the growth in demand for high quality stem cell products. CIRM, like all other agencies, will also have to evolve and adapt to these new demands. But we feel with the model we have created, and the flexibility we have to pivot when needed, we are perfectly situated to do just that.

Perseverance: from theory to therapy. Our story over the last year – and a half

Some of the stars of our Annual Report

It’s been a long time coming. Eighteen months to be precise. Which is a peculiarly long time for an Annual Report. The world is certainly a very different place today than when we started, and yet our core mission hasn’t changed at all, except to spring into action to make our own contribution to fighting the coronavirus.

This latest CIRM Annual Reportcovers 2019 through June 30, 2020. Why? Well, as you probably know we are running out of money and could be funding our last new awards by the end of this year. So, we wanted to produce as complete a picture of our achievements as we could – keeping in mind that we might not be around to produce a report next year.

Dr. Catriona Jamieson, UC San Diego physician and researcher

It’s a pretty jam-packed report. It covers everything from the 14 new clinical trials we have funded this year, including three specifically focused on COVID-19. It looks at the extraordinary researchers that we fund and the progress they have made, and the billions of additional dollars our funding has helped leverage for California. But at the heart of it, and at the heart of everything we do, are the patients. They’re the reason we are here. They are the reason we do what we do.

Byron Jenkins, former Naval fighter pilot who battled back from his own fight with multiple myeloma

There are stories of people like Byron Jenkins who almost died from multiple myeloma but is now back leading a full, active life with his family thanks to a CIRM-funded therapy with Poseida. There is Jordan Janz, a young man who once depended on taking 56 pills a day to keep his rare disease, cystinosis, under control but is now hoping a stem cell therapy developed by Dr. Stephanie Cherqui and her team at UC San Diego will make that something of the past.

Jordan Janz and Dr. Stephanie Cherqui

These individuals are remarkable on so many levels, not the least because they were willing to be among the first people ever to try these therapies. They are pioneers in every sense of the word.

Sneha Santosh, former CIRM Bridges student and now a researcher with Novo Nordisk

There is a lot of information in the report, charting the work we have done over the last 18 months. But it’s also a celebration of everyone who made it possible, and our way of saying thank you to the people of California who gave us this incredible honor and opportunity to do this work.

We hope you enjoy it.