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.
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.
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.
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.
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.
In the addition to the innovative scientists and clinicians who conceive and develop novel experimental therapies, it takes a village to drive a promising experimental therapy through phases of clinical trials, regulatory marketing approval, and commercialization before it becomes broadly accessible to patients with unmet medical needs. In this case, the village is the broader industry including institutional investors and biopharma companies that have the capital, resources and expertise to carry the development programs past the finish line.
A big part of what CIRM does revolves around nurturing projects at the very early stages. By providing funding and guidance through our collaborative team of experts, CIRM de-risks its therapy development programs through pre-clinical and clinical stages, thereby readying them for industry partnerships to support them through the last mile. CIRM funding to California academic institutions has enabled the launch of more than 40 spinout companies, one of which we will highlight below.
On April 7th, 2020, Forty Seven, Inc. was acquired by Gilead Sciences for $4.9 billion. CIRM funded the preclinical and early clinical development of an anti-CD47 antibody candidate for cancer at Stanford and subsequently funded two Forty Seven clinical trials. Now, Gilead will leverage all of its resources to accelerate the development of this promising cancer immunotherapy.
Dr. Mark Chao, Co-Founder, Forty Seven, Inc. had this to say about CIRM.
“CIRM’s support has been instrumental to our early successes and our ability to rapidly progress Forty Seven’s CD47 antibody targeting approach with magrolimab. CIRM was an early collaborator in our clinical programs and it’s support was instrumental in helping us reach a point where we could become a part of Gilead and move forward with our research.”
To proactively enable more partnering successes such as Forty Seven, CIRM has established the Industry Alliance Program (IAP) as a direct opportunity for the industry to partner with CIRM grantees in accelerating the most promising stem cell, gene and regenerative medicine therapy programs to commercialization. Through the IAP, CIRM is a dedicated and proactive partner to industry and CIRM grantees.
We recently launched a website for those interested in knowing more about these partnerships. It describes the IAP program in more detail can be accessed by clicking here.
If you are a potential industry partner wishing to learn more about CIRM’s IAP, please contact:
It’s not every day that a company and a concept that you helped support from the very beginning gets snapped up for $4.9 billion. But that’s what is happening with Forty Seven Inc. and their anti-cancer therapies. Gilead, another California company by the way, has announced it is buying Forty Seven Inc. for almost $5 billion.
The deal gives Gilead access to Forty Seven’s lead antibody therapy, magrolimab, which switches off CD47, a kind of “do not eat me” signal that cancer cells use to evade the immune system.
CIRM has supported this program from its very earliest stages, back in 2013, when it was a promising idea in need of funding. Last year we blogged about the progress it has made from a hopeful concept to an exciting therapy.
When Forty Seven Inc. went public in 2018, Dr. Irv Weissman, one of the founders of the company, attributed a lot of their success to CIRM’s support.
“The story of the funding of this work all of the way to its commercialization and the clinical trials reported in the New England Journal of Medicine is simply this: CIRM funding of a competitive grant took a mouse discovery of the CD47 ‘don’t eat me’ signal through all preclinical work to and through a phase 1 IND with the FDA. Our National Institutes of Health (NIH) did not fund any part of the clinical trial or preclinical run up to the trial, so it is fortunate for those patients and those that will follow, if the treatment continues its success in larger trials, that California voters took the state’s right action to fund research not funded by the federal government.”
Dr. Maria Millan, CIRM’s President & CEO, says the deal is a perfect example of CIRM’s value to the field of regenerative medicine and our ability to work with our grantees to make them as successful as possible.
“To say this is incredible would be an understatement! Words cannot describe how excited we are that this novel approach to battling currently untreatable malignancies has the prospect of making it to patients in need and this is a major step. Speaking on behalf of CIRM, we are very honored to have been a partner with Forty Seven Inc. from the very beginning.
CIRM Senior Science Officer, Dr. Ingrid Caras, was part of the team that helped a group of academic scientists take their work out of the lab and into the real world.
“I had the pleasure of working with and helping the Stanford team since CIRM provided the initial funding to translate the idea of developing CD47 blockade as a therapeutic approach. This was a team of superb scientists who we were fortunate to work closely with them to navigate the Regulatory environment and develop a therapeutic product. We were able to provide guidance as well as funding and assist in the ultimate success of this project.”
Forty Seven Inc. is far from the only example of this kind of support and collaboration. We have always seen ourselves as far more than just a funding agency. Money is important, absolutely. But so too is bringing the experience and expertise of our team to help academic scientists take a promising idea and turn it into a successful therapy.
After all that’s what our mission is, doing all we can to accelerate stem cell therapies to patients with unmet medical needs. And after a deal like this, Forty Seven Inc. is definitely accelerating its work.
An independent Economic Impact Report says the California Institute for Regenerative Medicine (CIRM) has had a major impact on California’s economy, creating tens of thousands of new jobs, generating hundreds of millions of dollars in new taxes, and producing billions of dollars in additional revenue for the state.
The report, done by Dan Wei and Adam Rose at the Price School of Public Policy at the University of Southern California, looked at the impacts of CIRM funding on both the state and national economy from the start of the Stem Cell Agency in 2004 to the end of 2018.
The total impacts on the California economy are estimated
billion of additional gross output (sales revenue)
million of additional state/local tax revenues
million of additional federal tax revenues
additional full-time equivalent (FTE) jobs, half of which offer salaries
considerably higher than the state average
Millan, M.D., CIRM’s President and CEO, says the report reflects the Agency’s
role in building an ecosystem to accelerate the translation of important stem
cell science to solutions for patients with unmet medical needs. “CIRM’s
mission on behalf of patients has been the priority from day one, but this
report shows that CIRM funding brings additional benefits to the state. This report
reflects how CIRM is promoting economic growth in California by attracting
scientific talent and additional capital, and by creating an environment that
supports the development of businesses and commercial enterprises in the state”
In addition to the benefits to California, the impacts
outside of California on the US economy are estimated to be:
billion of additional gross output (sales revenue)
million of additional state (non-Californian) & local tax revenue
million of additional federal tax revenues
additional full-time equivalent (FTE) jobs
researchers summarize their findings, saying: “In terms of economic impacts, the
state’s investment in CIRM has paid handsome dividends in terms of output, employment,
and tax revenues for California.”
The estimates in the report are based on the economic stimulus
created by CIRM funding and by the co-funding that researchers and companies
were required to provide for clinical and late-stage preclinical projects. The
estimates also include:
Investments in CIRM-supported projects from private funders such
as equity investments, public offerings and mergers and acquisitions,
Follow-on funding from the National Institutes of Health and other
organizations due to data generated in CIRM-funded projects
Funding generated by clinical trials held at CIRM’s Alpha Stem
Cell Clinics network
researchers state “Nearly half of these impacts emanate from the $2.67 billion
CIRM grants themselves.”
economic impact of California’s investment in stem and regenerative cell
research is reflective of significant progress in this field that was just
being born at the time of CIRM’s creation,” says Dr. Millan. “We fund the most
promising projects based on rigorous science from basic research into clinical
trials. We partnered with researchers and companies to increase the likelihood
of success and created specialized infrastructure such as the Alpha Clinics
Network to support the highest quality of clinical care and research standards
for these novel approaches. The
ecosystem created by CIRM has attracted scientists, companies and capital from outside
the state to California. By supporting promising science projects early on,
long before most investors were ready to come aboard, we enabled our scientists
to make progress that positioned them to attract significant commercial
investments into their programs and into California.”
think one of the greatest strengths of CIRM has been their focus on development
of new stem cell therapies that can become real medicines,” says UCLA and
Orchard Therapeutics’ Don Kohn, M.D. “This has meant guiding academic
investigators to do the things that may be second nature in
industry/pharmaceutical companies but are not standard for basic or clinical
research. The support from CIRM to perform the studies and regulatory
activities needed to navigate therapies through the FDA and to form alliances
with biotech and pharma companies has allowed the stem cell gene therapy we
developed to treat SCID babies to be advanced and licensed to Orchard
Therapeutics who can make it available to patients across the country.”
support has been instrumental to our early successes and our ability to rapidly
progress Forty Seven’s CD47 antibody targeting approach with magrolimab,” says
Mark Chao, M.D., Ph.D., Founder and Vice President of Clinical Development at
Forty Seven Inc. “ CIRM was an early collaborator in our clinical
programs, and will continue to be a valued partner as we move forward with our
MDS/AML clinical trials.”
researchers say the money generated by partnerships and investments, what is
called “deal-flow funding”, is still growing and that the economic benefits
created by them are likely to continue for some time: “Deal-flow funding
usually involves several waves or rounds of capital infusion over many years,
and thus is it expected that CIRM’s past and current funding will attract
increasing amounts of industry investment and lead to additional spending
injections into the California economy in the years to come.”
They conclude their report by saying: “CIRM has led to
California stem cell research and development activities becoming a leader
among the states.”
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are both types of blood cancers that can be difficult to treat. CIRM is fundingForty Seven, Inc. to conduct a clinical trial to treat patients with these blood cancers with an antibody called 5F9. CIRM has also given multiple awards prior to the clinical trial to help in developing the antibody.
Cancer cells express a signal known as CD47, which sends a “don’t eat me” message to macrophages, which are white blood cells that are part of the immune system designed to “eat” and destroy unhealthy cells. The antibody works by blocking the signal, enabling the body’s own immune system to detect and destroy the cancer cells.
In a press release, Forty Seven, Inc. announced early clinical results from their CIRM funded trial using the antibody to treat patients with AML and MDS. Some patients received just the antibody while others received the antibody in combination with azacitidine, a chemotherapy drug used to treat these cancers.
Here is a synopsis of the trial:
35 patients treated in a Phase 1 clinical trial have been evaluated for a response assessment to-date.
10 of these have MDS or AML and only received the 5F9 antibody.
11 of these have higher-risk MDS and received the 5F9 antibody along with the chemotherapy drug azacitidine.
14 of these have untreated AML and received the 5F9 antibody along with the chemotherapy drug azacitidine.
For the 11 patients with higher-risk MDS treated with the antibody and chemotherapy, they found that:
All 11 patients achieved an objective response rate (ORR),meaning that there was a reduction in tumor burden of a predefined amount.
Six of these patients achieved a complete response (CR), indicatinga disappearance of all signs of cancer in response to treatment.
For the 14 patients with untreated AML treated with the antibody and chemotherapy, they found that:
Nine of these patients achieved an ORR.
Five of theseninepatients achieved a CR.
Two of these nine patientsachieved a morphologic leukemia-free state (MLFS), indicating the disappearance of all cells with formal and structural characteristics of leukemia, accompanied by bone marrow recovery, in response to treatment.
The remaining five patients achieved stable disease (SD), meaning that the tumor is neither growing nor shrinking.
The results also showed that:
There was no evidence of increased toxicities when the antibody was used alongside the chemotherapy drugs, demonstrating tolerance and safety of the treatment.
No responding MDS or AML patient has relapsed or progressed on the antibody in combination with chemotherapy, with a median follow-up of 3.8 months.
The median time to response was rapid at 1.9 months.
Several patients have experienced deepening responses over time resulting in complete remissions.
Based on the favorable results observed in this clinical trial to-date, expansion cohorts have been initiated, meaning that additional patients will be enrolled in a phase I trial. This will include patients with both higher-risk MDS and untreated AML as well as using the antibody in combination with chemotherapy.
In the press release, Dr. David Sallman, an investigator in the clinical trial, is quoted as saying,
“These new data for 5F9 show encouraging clinical activity in a broad population of patients with MDS and AML, who may be unfit for existing therapeutic options or at higher-risk for developing rapidly-advancing disease. Despite an evolving treatment landscape, physicians continue to seek new therapies for MDS and AML that can be used safely in combination with standard-of-care to help patients more rapidly achieve durable responses. To that end, I am excited to see meaningful clinical activity in a majority of patients treated with 5F9 in combination with azacitidine, with a median time to response of under two months and no relapses or progressions among responding patients.”
The Golden State Warriors, the current US basketball champions – and your favorite Stem Cell Agency’s neighbors in Oakland – have a slogan, “Strength in Numbers”. That could well apply to the field of Regenerative Medicine because the field is growing in numbers, growing in strength, and growing in influence.
Yesterday, the Alliance for Regenerative Medicine (ARM), the organization that represents the field, held its annual State of the Industry briefing in San Francisco, detailing what happened in 2018. It was pretty impressive.
In fact, just the number of people in the room was impressive. More than 800 RSVP’d for the event, more than for any previous meeting, but even then the room was filled over capacity with many standing around the edges because there were no seats left.
ARM itself is growing, 32 percent last year, and now has more than 300 members. Other impressive numbers include:
906 gene and cell therapy companies worldwide
484 gene and cell therapy companies in the US alone
1,028 clinical trials taking place worldwide
598 of those clinical trials (58 percent of the total) are targeting cancer
59,575 patients are slated to be enrolled in those trials
All those numbers are up dramatically on last year. You can see all the details on the ARM website.
Another sign the industry is growing comes in the amount of money being invested. When people are willing to pony up hard cash you know it’s a sign they believe in you. Last year the field raised $13.8 billion worldwide, that’s up a whopping 73 percent on 2017. That represented a strong year across all fronts from corporate partnerships to Initial Public Offerings (several CIRM-supported companies such as Orchard Therapeutics and Forty Seven Inc. are in that number) and venture capital investments.
Clearly there are still challenges ahead, such as figuring out ways to pay for these therapies when they are approved so that they are available to the people who need them, the patients.
One of the issues that is going to be front and center in 2019 is reimbursement and developing new payment models. But that in itself is a sign of a maturing field. In past years the emphasis was on developing new treatments. Now that those are in the pipeline, we’re working on ways to pay for them.
The “Valley of Death” sounds like a scary place from “Lord of the Rings” or “Game of Thrones” that our heroes have to navigate to reach safety. The reality is not that different. It’s the space that young companies have to navigate from having a good idea to getting financial backing, so they can move their projects towards the clinic. At the other side of the Valley are deep-pocket investors, waiting to see what makes it through before deciding if they want to support them.
It’s a Catch 22 situation. Without financing companies can’t make it through the Valley; but they need to get through before the folks with money will considering investing. As a result many companies languish or even fail to make it through the Valley of Death. Without that financial support promising therapies are lost before they even get a chance to show their potential.
CIRM was created, in part, to help those great ideas get through the Valley. That’s why it is so gratifying to hear the news today from ViaCyte – that is developing a promising approach to treating type 1 diabetes – that they have secured $80 million in additional financing.
The money comes from Bain Capital Life Sciences, TPG and RA Capital Management and several other investors. It’s important because it is a kind of vote of confidence in ViaCyte, suggesting these deep-pocket investors believe the company’s approach has real potential.
In a news release Adam Koppel, a Managing Director at Bain, said:
“ViaCyte is the clear leader in beta cell replacement, and we are excited about the lasting impact that it’s stem cell-derived therapies can potentially have on improving treatment and quality of life for people living with insulin-requiring diabetes. We look forward to partnering with ViaCyte’s management team to accelerate the development of ViaCyte’s transformative cell therapies to help patients.”
CIRM has been a big supporter of ViaCyte for several years, investing more than $70 million to help them develop a cell therapy that can be implanted under the skin that is capable of delivering insulin to people with type 1 diabetes when needed. The fact that these investors are now stepping up to help it progress suggests we are not alone in thinking this project has tremendous promise.
But ViaCyte is far from the only company that has benefitted from CIRM’s early and consistent support. This year alone CIRM-funded companies have raised more than $1.0 billion in funding from outside investors; a clear sign of validation not just for the companies and their therapies, but also for CIRM and its judgement.
Humacyte raising $225 million for its program to help people battling kidney failure
Forty Seven Inc. raising $113 million from an Initial Public Offering for its programs targeting different forms of cancer
We have shown there is a path through the Valley of Death. We are hoping to lead many more companies through that in the coming years, so they can bring their therapies to people who really need them, the patients.
Sometimes even courage and determination are not enough. Karl Trede had courage and determination in droves as he fought a 12 year battle against cancer. He recently lost that battle. But he remains an inspiration for all who knew him.
I got to know Karl for our 2016 Annual Report. Karl had been diagnosed with throat cancer in 2006. He underwent surgery to remove his vocal cords and the cancer seemed to be in remission. But then it returned, this time having spread to his lungs. His doctors said they had pretty much run out of options but would Karl consider trying something new, something no one else had tried before; stem cells.
Karl told me he didn’t hesitate.
“I said “sure”. I don’t believe I knew at the time that I was going to be the first one but I thought I’d give it a whirl. It was an experience for me. It was eye opening. I wasn’t real concerned about being the first, I figured I was going to have to go someday so I guess if I was the first person and something really went wrong then they’d definitely learn something. So, to me, that was kind of worth my time.”
Happily nothing went wrong and the team behind the therapy (Forty Seven Inc.) definitely learned something, they learned a lot about the correct dosage for patients; invaluable information in treating future patients.
Karl’s cancer was held at bay and he was able to do the one thing that brought him more pleasure than anything else; spend time with his family, his wife Vita, their four sons and their families. He doted on his grand kids and got to see them grow, and they got to know him.
Recently the cancer returned and this time there was no holding it at bay. To the end Karl remained cheerful and positive.
In our office is a huge poster of Karl with the words “Every Moment Counts” at the bottom. It’s a reminder to us why we come to work every day, why the people at Forty Seven Inc. and all the other researchers we support work so hard for years and years; to try and give people like Karl a few extra moments with his family.
At the top of the poster the word “Courage” is emblazoned across it. Karl has a huge smile on his face. Karl was certainly courageous, a stem cell pioneer willing to try something no one else ever had. He was also very modest.
The context was the recent initial public offering (IPO) of Forty Seven Inc.. a company co-founded by Dr. Weissman. That IPO followed news that two Phase 2 clinical trials being run by Forty Seven Inc. were demonstrating promising results against hard-to-treat cancers.
Dr. Weissman says the therapies used a combination of two monoclonal antibodies, 5F9 from Forty Seven Inc. and Rituximab (an already FDA-approved treatment for cancer and rheumatoid arthritis) which:
“Led to about a 50% overall remission rate when used on patients who had relapsed, multi-site disease refractory to rituximab-plus-chemotherapy. Most of those patients have shown a complete remission, although it’s too early to tell if this is complete for life.”
5F9 attacks a molecule called CD47 that appears on the surface of cancer cells. Dr. Weissman calls CD47 a “don’t eat me signal” that protects the cancer against the body’s own immune system. By blocking the action of CD47, 5F9 strips away that “don’t eat me signal” leaving the cancer vulnerable to the patient’s immune system. We have blogged about this work here and here.
The news from these trials is encouraging. But what was gratifying about Dr. Weissman’s statement is his generosity in sharing credit for the work with CIRM.
Here is what he wrote:
“What is unusual about Forty Seven is that not only the discovery, but its entire preclinical development and testing of toxicity, etc. as well as filing two Investigational New Drug [IND] applications to the Food and Drug Administration (FDA) in the US and to the MHRA in the UK, as well as much of the Phase 1 trials were carried out by a Stanford team led by two of the discoverers, Ravi Majeti and Irving Weissman at Stanford, and not at a company.
The major support came from the California Institute of Regenerative Medicine [CIRM], funded by Proposition 71, as well as the Ludwig Cancer Research Foundation at the Ludwig Center for Cancer Stem Cell Research at Stanford. CIRM will share in downstream royalties coming to Stanford as part of the agreement for funding this development.
This part of the state initiative, Proposition 71, is highly innovative and allows the discoverers of a field to guide its early phases rather than licensing it to a biotech or a pharmaceutical company before the value and safety of the discovery are sufficiently mature to be known. Most therapies at early-stage biotechs are lost in what is called the ‘valley of death’, wherein funding is very difficult to raise; many times the failure can be attributed to losing the expertise of the discoverers of the field.”
Dr. Weissman also had praise for CIRM’s funding model which requires companies that produce successful, profitable therapies – thanks to CIRM support – to return a portion of those profits to California. Most other funding agencies don’t have those requirements.
“US federal funds, from agencies such as the National Institutes of Health (NIH) similarly support discovery but cannot fund more than a few projects to, and through, early phase clinical trials. And, under the Bayh-Dole Act, the universities keep all of the equity and royalties derived from licensing discoveries. In that model no money flows back to the agency (or the public), and nearly a decade of level or less than level funding (at the national level) has severely reduced academic research. So this experiment of funding (the NIH or the CIRM model) is now entering into the phase that the public will find out which model is best for bringing new discoveries and new companies to the US and its research and clinical trials community.”
We have been funding Dr. Weissman’s work since 2006. In fact, he was one of the first recipients of CIRM funding. It’s starting to look like a very good investment indeed.
Thelma, participant in the CAMELLIA clinical trial
You have almost certainly never heard of Thelma, or met her, or know anything about her. She’s a lady living in England who, if it wasn’t for a CIRM-funded therapy, might not be living at all. She’s proof that what we do, is helping people.
Thelma is featured in a video about a treatment for acute myeloid leukemia, one of the most severe forms of blood cancer. Thelma took part in a clinical trial, called CAMELLIA, at Oxford Cancer Centre in Oxford, UK. The clinical trial uses a therapy that blocks a protein called CD47 that is found on the surface of cancer cells, including cancer stem cells which can evade traditional therapies. The video was shot to thank the charity Bloodwise for raising the funds to pay for the trial.
Prof. Paresh Vyas of Oxford University, who was part of the clinical trial team that treated Thelma, says patients with this condition face long odds.
“Patients with acute myeloid leukemia have the most aggressive blood cancer. We really haven’t had good treatments for this condition for the last 40 years.”
While this video was shot in England, featuring English nurses and doctors and patients, the therapy itself was developed here in California, first at Stanford University under the guidance of Irv Weissman and, more recently, at Forty Seven Inc. That company is now about to test their approach in a CIRM-funded clinical trial here in the US.
This is an example of how CIRM doesn’t just fund research, we invest in it. We help support it at every stage, from the earliest research through to clinical trials. Without our early support this work may not have made it this far.
The Forty Seven Inc. therapy uses the patient’s own immune system to help fight back against cancer stem cells. It’s looking very promising. But you don’t have to take our word for it. Take Thelma’s.