Transplanted stem cells used to grow fully functional lungs in mice

Illustration of a human lung

According to organ donation statistics from the Health Resources & Services Administration, over 113,000 men, women, and children are on the national transplant waiting list as of July 2019. Another person is added to the waiting list every 10 minutes and 20 people die each day waiting for a transplant.

As these statistics highlight, there is a tremendous need for obtaining viable organs for people that are in need of a transplant. It is because of this, that scientists and researchers are exploring ways of using stem cells to potentially grow fully functional organs.

Dr. Hiromitsu Nakauchi, Stanford University

In a CIRM-supported study, Dr. Hiromitsu Nakauchi at Stanford University, in collaboration with Dr. Wellington Cardoso at Columbia University, were able to grow fully functional lungs in mouse embryos using transplanted stem cells. The full study, published in Nature Medicine, suggests that it may be possible to grow human lungs in animals and use them for patients in dire need of transplants or to study new lung treatments.

In the study, the researchers took stem cells and implanted them into modified mouse embryos that either lacked the stem cells necessary to form a lung or were not able to produce enough cells to make a lung. It was found that the implanted stem cells formed fully functional lungs that allowed the mice to live well into adulthood. Additionally, there were no signs of the mouse’s body rejecting the lung tissue composed of donor stem cells.

In a press release, Dr. Cardoso expressed optimism for the study and the potential the results hold:

“Millions of people worldwide who suffer from incurable lung diseases die without treatment due to the limited supply of donor lungs for transplantation. Our study shows that it may eventually be possible to develop new strategies for generating human lungs in animals for transplantation as an alternative to waiting for donor lungs.”

The challenges of living with IPEX

Last week the CIRM Board awarded $5.53 million to Dr. Rosa Bacchetta at Stanford to complete the work necessary to conduct a clinical trial for IPEX syndrome. This is a rare disease caused by mutations in the FOXP3 gene which leaves people with the condition vulnerable to immune system attacks on their organs and tissues. These attacks can be devastating, even fatal.

At the Board meeting Taylor Lookofsky, a young man with IPEX syndrome, talked about the impact the condition has had on his life. The transcript of his talk is below.

It’s a powerful reminder that syndromes like this, because they affect a small number of people, are often overlooked and have few resources devoted to finding new treatments and cures. After reading Taylor’s story you come to appreciate his courage and determination, and why the funding CIRM provides is so important in helping researchers like Dr. Bacchetta find therapies to help people like Taylor.

Brian Lookofsky (Taylor’s father), Taylor Lookofsky and Dr. Rosa Bacchetta at the CIRM Board meeting

“Good morning, my name is Taylor Lookofsky and I would first like to thank Rosa, who is one of the many doctors in my life. Rosa presented me with this amazing opportunity to come and speak to you today about my life and the challenges living with IPEX.

  • I’d like to give you some background into my health challenges I’ve faced my entire life. Now to give some context to my years of struggle, I am 28 years old, not 10 years younger as some may have assumed.
  • My first diagnosis came at the age of 1 ½ years old -type 1 diabetes.
  • Soon after being diagnosed with type 1 diabetes, I had to have a feeding tube inserted in my abdomen as I was restricted from eating almost all foods due to unknown food allergies. I was not allowed to ingest ANY food until the age of 6 years old. When I was finally introduced to food, any food ingested was tasteless and felt like sandpaper on my tongue since I had to train myself to eat.
  • Around age 10, I would be faced with the beginning of a never-ending battle with my dermatitis. I remember specific details where my mother had taken me to a dermatologist to try and figure out what was happening to my skin as it was red, blotchy, oozing. I remember shivering so badly that my mom had to ask the doctor’s office to turn the air down.
  • At age 18 I had been formally diagnosed with IPEX. I lost my hair and my skin started a battle that was more intense than any previous episode. I remember taking showers and clumps of my hair would fall out, and I would cry in the shower not knowing what was going on.
  • At age 20, I would go through the most horrific episode with my skin to date. I was bed ridden, on pain meds and could not sleep. I had gone to all of my doctors trying to figure out what had triggered this event, and no doctor could figure out what was happening, leaving me extremely frustrated, depressed and drained of all energy. I went to the burn center as a last resort and was then treated like a burn patient. To care for these wounds, I would bathe, take a sponge and physically scrape these wounds to keep them infection free and as clean as possible. When I would exit the bath, I felt like a dried-up sponge and my skin was so tight that any movement would make my skin crack open and start bleeding. To add to this, I had to use medicated wraps to help with the healing process.
  • In an ongoing attempt to treat my many symptoms, I took a series of medications that came with side effects. I have had at least 15 surgeries to remove squamous cells caused by one of the medications: In 2018, my colon perforated. As a result, I now have a colostomy bag.

The IPEX symptoms have affected me not just physically, but mentally as well. I had lost all my hair and growth has been permanently stunted, and I have not reached the point in puberty as my male counterparts. I would go day by day and see all my peers and be envious that they were tall, had beards and hair, had relationships, and the confidence that I was lacking and admittedly, still lack to this day at times.

I’ve felt hopeless because there have been so few treatment options and with the treatment currently available, I have tried hundreds of medications and creams, and have had my blood drawn countless times in hopes of finding a medication that works for me, or a cure for this insufferable disease. However, nothing. As a result, I have been battling depression singe age 20. There were days that went by where I thought “I just don’t want to be here if this is what life is going to be like.” 

The funding needed for Dr. Rosa’s therapy would be life changing in the way of new treatment options and potentially lead to a cure for this horrific disease.

I am determined to see that there is so much more to life than what society is telling me. I’ve decided that I would not conform to societies rules, and instead, tell society how I am going to live my unique and authentic life with IPEX.

I appreciate your time and consideration to fund this important research.”

CIRM Board Awards $15.8 Million to Four Translational Research Projects

Last week, the CIRM Board approved $32.92 million in awards directed towards four new clinical trials in vision related diseases and Parkinson’s Disease.

In addition to these awards, the Board also approved investing $15.80 million in four awards in the Translational Research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.

Before we go into more specific details of each one of these awards, here is a table summarizing these four new projects:

ApplicationTitleInstitutionAward Amount
TRAN1 11536Ex Vivo Gene Editing of Human Hematopoietic Stem Cells for the Treatment of X-Linked Hyper IgM Syndrome  UCLA $4,896,628
TRAN1 11555BCMA/CS1 Bispecific CAR-T Cell Therapy to Prevent Antigen Escape in Multiple Myeloma  UCLA $3,176,805
TRAN1 11544 Neural Stem cell-mediated oncolytic immunotherapy for ovarian cancer  City of Hope $2,873,262
TRAN1 11611Development of a human stem cell-derived inhibitory neuron therapeutic for the treatment of chronic focal epilepsyNeurona Therapeutics$4,848,750
Dr. Caroline Kuo, UCLA

$4.89 million was awarded to Dr. Caroline Kuo at UCLA to pursue a gene therapy approach for X-Linked Hyper IgM Syndrome (X-HIM).

X-HIM is a hereditary immune disorder observed predominantly in males in which there are abnormal levels of different types of antibodies in the body.  Antibodies are also known as Immunoglobulin (Ig) and they combat infections by attaching to germs and other foreign substances, marking them for destruction.  In infants with X-HIM, there are normal or high levels of antibody IgM but low levels of antibodies IgG, IgA, and IgE.  The low level of these antibodies make it difficult to fight off infection, resulting in frequent pneumonia, sinus infections, ear infections, and parasitic infections.  Additionally, these infants have an increased risk of cancerous growths. 

The gene therapy approach Dr. Kuo is continuing to develop involves using CRISPR/Cas9 technology to modify human blood stem cells with a functional version of the gene necessary for normal levels of antibody production.  The ultimate goal would be to take a patient’s own blood stem cells, modify them with the corrected gene, and reintroduce them back into the patient.

CIRM has previously funded Dr. Kuo’s earlier work related to developing this gene therapy approach for XHIM.

Dr. Yvonne Chen, UCLA

$3.17 million was awarded to Dr. Yvonne Chen at UCLA to develop a CAR-T cell therapy for multiple myeloma (MM).

MM is a type of blood cancer that forms in the plasma cell, a type of white blood cell that is found in the bone marrow.  An estimated 32,110 people in the United States will be diagnosed with MM in 2019 alone.  Several treatment options are available to patients with MM, but there is no curative therapy.

The therapy that Dr. Chen is developing will consist of a genetically-modified version of the patient’s own T cells, which are an immune system cell that can destroy foreign or abnormal cells.  The T cells will be modified with a protein called a chimeric antigen receptor (CAR) that will recognize BCMA and CS1, two different markers found on the surface of MM cells.  These modified T cells (CAR-T cells) are then infused into the patient, where they are expected to detect and destroy BCMA and CS1 expressing MM cells.

Dr. Chen is using CAR-T cells that can detect two different markers in a separate clinical trial that you can read about in a previous blog post.

Dr. Karen Aboody, City of Hope

$2.87 million was awarded to Dr. Karen Aboody at City of Hope to develop an immunotherapy delivered via neural stem cells (NSCs) for treatment of ovarian cancer.

Ovarian cancer affects approximately 22,000 women per year in the United States alone.  Most ovarian cancer patients eventually develop resistance to chemotherapy, leading to cancer progression and death, highlighting the need for treatment of recurring ovarian cancer.

The therapy that Dr. Aboody is developing will use an established line of NSCs to deliver a virus that specifically targets these tumor cells.  Once the virus has entered the tumor cell, it will continuously replicate until the cell is destroyed.  The additional copies of the virus will then go on to target neighboring tumor cells.  This process could potentially stimulate the body’s own immune response to fight off the cancer cells as well.

Dr. Cory Nicholas, Neurona Therapeutics

$4.85 million was awarded to Dr. Cory Nicholas at Neurona Therapeutics to develop a treatment for epilepsy.

Epilepsy affects more than 3 million people in the United States with about 150,000 newly diagnosed cases in the US every year. It results in persistent, difficult to manage, or uncontrollable seizures that can be disabling and significantly impair quality of life. Unfortunately, anti-epileptic drugs fail to manage the disease in a large portion of people with epilepsy. Approximately one-third of epilepsy patients are considered to be drug-resistant, meaning that they do not adequately respond to at least two anti-epileptic drugs.

The therapy that Dr. Nicholas is developing will derive interneurons from human embryonic stem cells (hESCs). These newly derived interneurons would then be delivered to the brain via injection whereby the new cells are able to help regulate aberrant brain activity and potentially eliminate or significantly reduce the occurrence of seizures.

CIRM has previously funded the early stage development of this approach via a comprehensive grant and discovery grant.

Stem Cell Agency Approves Funding for Clinical Trials Targeting Parkinson’s Disease and Blindness

The governing Board of the California Institute for Regenerative Medicine (CIRM) yesterday invested $32.92 million to fund the Stem Cell Agency’s first clinical trial in Parkinson’s disease (PD), and to support three clinical trials targeting different forms of vision loss.

This brings the total number of clinical trials funded by CIRM to 60.

The PD trial will be carried out by Dr. Krystof Bankiewicz at Brain Neurotherapy Bio, Inc. He is using a gene therapy approach to promote the production of a protein called GDNF, which is best known for its ability to protect dopaminergic neurons, the kind of cell damaged by Parkinson’s. The approach seeks to increase dopamine production in the brain, alleviating PD symptoms and potentially slowing down the disease progress.

David Higgins, PhD, a CIRM Board member and patient advocate for Parkinson’s says there is a real need for new approaches to treating the disease. In the US alone, approximately 60,000 people are diagnosed with PD each year and it is expected that almost one million people will be living with the disease by 2020.

“Parkinson’s Disease is a serious unmet medical need and, for reasons we don’t fully understand, its prevalence is increasing. There’s always more outstanding research to fund than there is money to fund it. The GDNF approach represents one ‘class’ of potential therapies for Parkinson’s Disease and has the potential to address issues that are even broader than this specific therapy alone.”

The Board also approved funding for two clinical trials targeting retinitis pigmentosa (RP), a blinding eye disease that affects approximately 150,000 individuals in the US and 1.5 million people around the world. It is caused by the destruction of light-sensing cells in the back of the eye known as photoreceptors.  This leads to gradual vision loss and eventually blindness.  There are currently no effective treatments for RP.

Dr. Henry Klassen and his team at jCyte are injecting human retinal progenitor cells (hRPCs), into the vitreous cavity, a gel-filled space located in between the front and back part of the eye. The proposed mechanism of action is that hRPCs secrete neurotrophic factors that preserve, protect and even reactivate the photoreceptors, reversing the course of the disease.

CIRM has supported early development of Dr. Klassen’s approach as well as preclinical studies and two previous clinical trials.  The US Food and Drug Administration (FDA) has granted jCyte Regenerative Medicine Advanced Therapy (RMAT) designation based on the early clinical data for this severe unmet medical need, thus making the program eligible for expedited review and approval.

The other project targeting RP is led by Dr. Clive Svendsen from the Cedars-Sinai Regenerative Medicine Institute. In this approach, human neural progenitor cells (hNPCs) are transplanted to the back of the eye of RP patients. The goal is that the transplanted hNPCs will integrate and create a protective layer of cells that prevent destruction of the adjacent photoreceptors. 

The third trial focused on vision destroying diseases is led by Dr. Sophie Deng at the University of California Los Angeles (UCLA). Dr. Deng’s clinical trial addresses blinding corneal disease by targeting limbal stem cell deficiency (LSCD). Under healthy conditions, limbal stem cells (LSCs) continuously regenerate the cornea, the clear front surface of the eye that refracts light entering the eye and is responsible for the majority of the optical power. Without adequate limbal cells , inflammation, scarring, eye pain, loss of corneal clarity and gradual vision loss can occur. Dr. Deng’s team will expand the patient’s own remaining LSCs for transplantation and will use  novel diagnostic methods to assess the severity of LSCD and patient responses to treatment. This clinical trial builds upon previous CIRM-funded work, which includes early translational and late stage preclinical projects.

“CIRM funds and accelerates promising early stage research, through development and to clinical trials,” says Maria T. Millan, MD, President and CEO of CIRM. “Programs, such as those funded today, that were novel stem cell or gene therapy approaches addressing a small number of patients, often have difficulty attracting early investment and funding. CIRM’s role is to de-risk these novel regenerative medicine approaches that are based on rigorous science and have the potential to address unmet medical needs. By de-risking programs, CIRM has enabled our portfolio programs to gain significant downstream industry funding and partnership.”

CIRM Board also awarded $5.53 million to Dr. Rosa Bacchetta at Stanford to complete work necessary to conduct a clinical trial for IPEX syndrome, a rare disease caused by mutations in the FOXP3 gene. Immune cells called regulatory T Cells normally function to protect tissues from damage but in patients with IPEX syndrome, lack of functional Tregs render the body’s own tissues and organs to autoimmune attack that could be fatal in early childhood.  Current treatment options include a bone marrow transplant which is limited by available donors and graft versus host disease and immune suppressive drugs that are only partially effective. Dr. Rosa Bacchetta and her team at Stanford will use gene therapy to insert a normal version of the FOXP3 gene into the patient’s own T Cells to restore the normal function of regulatory T Cells.

The CIRM Board also approved investing $15.80 million in four awards in the Translational Research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.

The TRAN1 Awards are summarized in the table below:

ApplicationTitleInstitutionAward Amount
TRAN1 11536Ex Vivo Gene Editing of Human Hematopoietic Stem Cells for the Treatment of X-Linked Hyper IgM Syndrome  UCLA $4,896,628
TRAN1 11555BCMA/CS1 Bispecific CAR-T Cell Therapy to Prevent Antigen Escape in Multiple Myeloma  UCLA $3,176,805
TRAN1 11544 Neural Stem cell-mediated oncolytic immunotherapy for ovarian cancer  City of Hope $2,873,262
TRAN1 11611Development of a human stem cell-derived inhibitory neuron therapeutic for the treatment of chronic focal epilepsyNeurona Therapeutics$4,848,750

How early CIRM support helped an anti-cancer therapy overcome obstacles and help patients

Dr. Catriona Jamieson, UC San Diego

When you read about a new drug or therapy being approved to help patients it always seems so simple. Researchers come up with a brilliant idea, test it to make sure it is safe and works, and then get approval from the US Food and Drug Administration (FDA) to sell it to people who need it.

But it’s not always that simple, or straight forward. Sometimes it can take years, with several detours along the way, before the therapy finds its way to patients.

That’s the case with a blood cancer drug called fedratinib (we blogged about it here) and the relentless efforts by U.C. San Diego researcher Dr. Catriona Jamieson to help make it available to patients. CIRM funded the critical early stage research to help show this approach could help save lives. But it took many more years, and several setbacks, before Dr. Jamieson finally succeeded in getting approval from the FDA.

The story behind that therapy, and Dr. Jamieson’s fight, is told in the San Diego Union Tribune. Reporter Brad Fikes has been following the therapy for years and in the story he explains why he found it so fascinating, and why this was a therapy that almost didn’t make it.

A bridge to the future: training the next generation of stem cell scientists

At CIRM we don’t just invest in stem cell research, we invest in people. One prime example of that is our Bridges to Stem Cell Research program. This is helping train the next generation of scientists by preparing Californian undergraduate and master’s students for careers in stem cell research.

The students who go through the Bridges program get up to a year-long internship, hands-on training and education in stem cell research. Just as importantly, they also get to work directly with patients to help them understand why we do this work; to help people in need.

One of our recent Bridges graduates is Zach Wagoner. Zach was a biology student and wondering what to do next to help him get some experience for a job when someone told him about the Bridges program. That set him on a course that is changing his life.

So how did the random conversation impact Zach? The team at the UC Irvine Sue and Bill Gross Stem Cell Research Center shot this video to answer that question.

It’s not just Zach who benefited from the program.  Of the 1257 alumni who graduated from the program by March of this year: 

  • 50% are working full time in academic or biotech research related positions
  • 30% enrolled in graduate or professional school

We think it’s been a wise investment.

USC study shows how tumor cells in the bloodstream can target distant organs

Various types of cancer can become particularly aggressive and difficult to treat once they spread from their initial point of origin to other parts of the body. This unfortunate phenomenon, known as metastasis, can make treatment very challenging, decreasing the chance of survival for the patient.

In order to better understand this process, a CIRM supported study at USC looked at breast cancer cells circulating in the blood that eventually invade the brain. The findings, which appear in Cancer Discovery, shed light on how tumor cells in the blood are able to target a particular organ, which may enable the development of treatments than can prevent metastasis from occurring.

Dr. Min Yu

Dr. Min Yu and her lab at USC were able to isolate breast cancer cells from the blood of breast cancer patients whose cancer had already metastasized. The team then expanded the number of cancer cells through a process known as cell culture. These expanded human tumor cells were then injected into the bloodstream of animal models. It was found that these cells migrated to the brain as was predicted.

Upon further analysis, Dr. Yu and her lab discovered a protein on the surface of the tumor cells in the bloodstream that enable them to breach the blood brain barrier, a protective layer around the brain that blocks the passage of certain substances, and enter the brain. Additionally, Dr. Yu and her team discovered another protein inside the tumor cells that shield them from the brain’s immune response, enabling these cells to grow inside the brain.

In a news release in Science Magazine, Dr. Yu talks about how these findings could be used to improve treatment and prevention options for those with aggressive cancers:

“We can imagine someday using the information carried by circulating tumor cells to improve the detection, monitoring and treatment of the spreading cancers. A future therapeutic goal is to develop drugs that get rid of circulating tumor cells or target those molecular signatures to prevent the spread of cancer.”

CIRM has also funded a separate clinical trial related to the treatment of breast cancer related brain metastases.

CIRM funded research could lead to treatment to prevent recurrence of deadly blood cancer

Chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is a cancer of the white blood cells. It causes them to increase in number, crowd out other blood cells, leading to anemia, infection or heavy bleeding. Up until the early 2000’s the main weapon against CML was chemotherapy, but the introduction of drugs called tyrosine kinase inhibitors changed that, dramatically improving long term survival rates.

However, these medications are not a cure and do not completely eradicate the leukemia stem cells that can fuel the growth of the cancer, so if people stop taking the medication the cancer can return.

Dr. John Chute: Photo courtesy UCLA

But now Dr. John Chute and a team of researchers at UCLA, in a CIRM-supported study, have found a way to target those leukemia stem cells and possibly eliminate them altogether.

The team knew that mice that had the genetic mutation responsible for around 95 percent of CML cases normally developed the disease and died with a few months. However, mice that had the CML gene but lacked another gene, one that produced a protein called pleiotrophin, had normal white blood cells and lived almost twice as long. Clearly there was something about pleiotrophin that played a key role in the growth of CML.

They tested this by transplanting blood stem cells from mice with the CML gene into healthy mice. The previously healthy mice developed leukemia and died. But when they did the same thing from mice that had the CML gene but lacked the pleiotrophin gene, the mice remained healthy.

So, Chute and his team wanted to know if the same thing happens in human cells. Studying human CML stem cells they found these had not just 100 times more pleiotrophin than ordinary cells, they were also producing their own pleiotrophin.

In a news release Chute, said this was unexpected:

“This provides an example of cancer stem cells that are perpetuating their own disease growth by hijacking a protein that normally supports the growth of the healthy blood system.”

Next Chute and the team developed an antibody that blocked the action of pleiotrophin and when they tested it in human cells the CML stem cells died.

Then they combined this antibody with a drug called imatinib (better known by its brand name, Gleevec) which targets the genetic abnormality that causes most forms of CML. They tested this in mice who had been transplanted with human CML stem cells and the cells died.

“Our results suggest that it may be possible to eradicate CML stem cells by combining this new targeted therapy with a tyrosine kinase inhibitor,” said Chute. “This could lead to a day down the road when people with CML may not need to take a tyrosine kinase inhibitor for the rest of their lives.”

The next step is for the researchers to modify the antibody so that it is better suited for humans and not mice and to see if it is effective not just in cells in the laboratory, but in people.

The study is published in the Journal of Clinical Investigation

Encouraging Progress for Two CIRM Supported Clinical Trials

This past Wednesday was Stem Cell Awareness Day, a day that is meant to remind us all of the importance of stem cell research and the potential it has to treat a wide variety of diseases. On this day, we also released an independent Economic Impact Report that showed how $10.7 Billion (yes, you read that right) was generated as a direct result of the the legacy we have built as a state agency that funds groundbreaking research.

Aside from the monetary incentive, which is an added bonus, the research we fund has made encouraging progress in the scientific field and has demonstrated the positive impact it can have on various disease areas. This week, two clinical trials supported by CIRM funding have released very promising updates.

Duchenne Muscular Dystrophy

Capricor Therapeutics, Inc. has presented positive results for a clinical trial related to a treatment for duchenne muscular dystrophy (DMD), a genetic disorder. DMD leads to progressive muscle degeneration and weakness due to its effect on a protein called dystrophin, which helps keep muscle cells intact.

The treatment that Capricor is testing is called CAP-1002 and consists of a unique population of cells that contain cardiac progenitor cells, a type of stem cell, that help encourage the regeneration of cells. CIRM funded an earlier clinical trial for this treatment.

The early results of this current trial describe how teens and young men in the advanced stages of DMD saw improvements in skeletal, lung, and heart measurements after receiving multiple doses of the treatment.

In a news release, Dr. Linda Marban, Chief Executive Officer of Capricor, expresses optimism for this clinical trial by saying,

“We are very pleased that the interim analysis from this double-blind placebo-controlled study, has demonstrated meaningful improvements across three clinically relevant endpoints in older patients with limited remaining treatment options.”

In the same news release, Dr. Craig McDonald, the national principal investigator for the trial, echoes the same sentiment by stating,

“The results from this trial to date are very promising in that the cells appear to positively impact skeletal, pulmonary and cardiac assessments in older DMD patients who have few, if any, remaining treatment options. We are eager to meet with the FDA to discuss the next steps for this promising program.”

Mantle Cell Lymphoma

Additionally, Oncternal Therapeutics has decided, because of positive results, to open an expansion of its CIRM-funded clinical trial aimed at treating patients with mantle cell lymphoma (MCL). The treatment involves an antibody called cirmtuzumab, named after us, in combination with a drug called ibrutinib.

The preliminary results were from the first six patients with MCL that were treated in the trial. One patient with MCL, who had relapsed following an allogeneic stem cell transplant, experienced a confirmed complete response (CR) after three months of cirmtuzumab plus ibrutinib treatment. This complete response appears to be sustained and has been confirmed to be ongoing after completing 12 months of the combination treatment. A second confirmed complete response occurred in a patient who had progressive disease after failing several different chemotherapy regimens, bone marrow transplant and CAR-T therapy. 

In a news release, Dr. Hun Lee, an investigator in the trial, states that,

“It is encouraging to see that the drug has been well tolerated as well as the early signal of efficacy of cirmtuzumab with ibrutinib in MCL, particularly the rapid and durable complete responses of the heavily pre-treated patients after three months of therapy, which is an unusually fast response in this patient population.”

New Report Says CIRM Produces Big Economic Boost for California

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 to be:

  • $10.7 billion of additional gross output (sales revenue)
  • $641.3 million of additional state/local tax revenues
  • $726.6 million of additional federal tax revenues
  • 56,549 additional full-time equivalent (FTE) jobs, half of which offer salaries considerably higher than the state average

Maria 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:

  • $4.7 billion of additional gross output (sales revenue)
  • $198.7 million of additional state (non-Californian) & local tax revenue
  • $208.6 million of additional federal tax revenues
  • 25,816 additional full-time equivalent (FTE) jobs

The 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

The researchers state “Nearly half of these impacts emanate from the $2.67 billion CIRM grants themselves.”

“The 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.”

These partnerships have helped move promising therapies out of the lab and into clinical trials for companies like Orchard Therapeutics’ successful treatment for Severe Combined Immunodeficiency and Forty Seven Inc.’s innovative approach to treating cancer.

Dr. Don Kohn: Photo courtesy UCLA Jonsson Comprehensive Cancer Center

“I 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.”

Dr. Mark Chao: Photo courtesy Forty Seven Inc.

“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,” 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.”

The 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.”