CIRM Board Meeting Highlights Important Updates to Clinical Trials

Dr. Maria T. Millan, President and CEO of CIRM, presenting the President’s Report

This past Thursday the governing Board of the California Institute for Regenerative Medicine (CIRM) were presented with an update on CIRM’s clinical portfolio, which to date includes 60 clinical trials in various areas including kidney failure, cancer, and other rare diseases.  The full President’s Report gives an update on 15 of these trials, in addition to our landmark Cure Sickle Cell Initiative with the NIH and our various educational programs.

Although we won’t be diving into extensive detail for all of these trials, we wanted to highlight several key updates made in this presentation to demonstrate how our clinical portfolio is maturing, with many of these trials moving towards registration. Classically, registration trials are large Phase 3 trials. Notably, some of the highlighted CIRM trials are small Phase 2 or earlier trials that seek to gain enough safety and efficacy data to support final FDA marketing approval. This is a trend with regenerative medicine programs where trial sizes are often small due to the fact that the affected populations are so small with some of these rare diseases. Despite this, the approaches could allow a so called “large effect size,” meaning the signal of clinical benefit per patient is strong enough to give a read of whether the therapy is working or not. CIRM programs often address rare unmet needs and utilize this approach.

For example, Orchard Therapeutics, which is conducting a phase 2 clinical trial for ADA Severe Combined Immunodeficiency (ADA-SCID), a rare immune disorder caused by a genetic mutation, has shown a long-term recovery of the immune system in 20 patients two years post treatment.  Orchard plans to submit a Biologics License Application (BLA) sometime in 2020, which is the key step necessary to obtain final approval from the Food and Drug Administration (FDA) for a therapy.

“We are thrilled to see encouraging results for this genetically modified cell therapy approach and a path forward for FDA approval,” says Maria T. Millan, MD, President and CEO of CIRM. “CIRM is proud of the role it has played in this program.  We funded the program while it was at UCLA and it is now in partnership with Orchard Therapeutics as it takes the program through this final phase toward FDA marketing approval.  Success in this program is a game changer for patients with ADA-SCID who had no other options and who had no bone marrow transplant donors. It also opens up possibilities for future approaches for this dieaseas as well as the other 6,000 genetic diseases that currently have no treatment.”    

The trial uses a gene therapy approach that takes the patient’s own blood stem cells, introduces a functional version of the ADA gene, and reintroduces these corrected blood stem cells back into the patient. From blood tests, one can readily detect whether the approach is successful from the presence of ADA and from the presence of immune cells that were not previously present. To date, it has been awarded approximately $19 million in CIRM funding.  Additionally, it has received FDA Breakthrough Therapy as well as Orphan Drug Designations, both of which are designed to accelerate  the development of the treatment.

Another trial that was highlighted is Rocket Pharmaceutical’s clinical trial for Leukocyte Adhesion Deficiency-1 (LAD-1), a rare and fatal pediatric disease that affects the body’s ability to combat infections. They have just released initial results from their first patient. This is also a gene therapy approach using the patient’s own blood stem cells. The notable aspect of this trial is that the investigators designed this small phase 1 trial of nine patients to be “registration enabling.”  This means that, if they find compelling data, they intend to bring the experience and data from this trial to the FDA to seek agreement on what would be required to get final marketing approval in order to get this treatment to patients with severe unmet medical needs in the most timely way possible.     

Preliminary results demonstrate early evidence of safety and potential efficacy.  There were visible improvements in multiple disease-related skin lesions after receiving the therapy. They are collecting more data on more patients.  To date, it has received $6.6 million in CIRM funding.

As a unique immuno-oncology approach (using the body’s immune system to battle cancer), CIRM is funding Forty Seven Inc. to conduct a clinical trial for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), both of which are forms of cancer.  They have received Fast Track and Orphan Drug designation from the FDA.

The trial is using an antibody blocking CD47, a “don’t eat me” signal, which allows the body’s own immune cells to seek and destroy cancerous stem cells.  This is combined with chemotherapy to render the cancer stem cells more susceptible to immune destruction.  This trial has received $5 million in CIRM funding thus far.

Other registration phase trials in the CIRM portfolio include the following Phase 3 trials:

Brainstorm Cell Therapeutics, for a fatal debilitating neurodegenerative disease, Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease).  That company has completed enrollment and expects top line results in the final quarter of 2020.

Humacyte, which is testing bioengineered de-cellularized vessels that are implanted to create vascular access that is repopulated by the patients own stem cells to make it more like native vessel.  The company is conducting two Phase 3 trials to compare this bioengineered vessel to synthetic grafts and to the patients’ own vessels for use in hemodialysis, a “life line” for patients with end stage renal disease. Humacyte was the first US FDA Cell Therapy program to receive the Regenerative Medicine Advanced Technologies (RMAT) in March 2017. To date, these trials have been awarded $24 million in CIRM funding.

Medeor Therapeutics has received $11.2M in CIRM funding to conduct a Phase 3 trial in combined blood stem cell and kidney transplantation to induce immunologic tolerance so that the blood stem cells teach the patient’s immune system to recognize the transplanted kidney as its own.  The goal is to remove the need for chronic immunosuppressive medications, that have its own complications. If successful, transplant recipients would not need to “trade one chronic condition for another.”

CIRM’s Alpha Stem Cell Clinics Given High Profile Role in Clinical Trials Network

Sue and Bill Gross Hall Photo by Hoang Xuan Pham/ UC Irvine

There are a growing number of predatory clinics in California and around the US, offering unproven stem cell therapies. For patients seeking a legitimate therapy it can often be hard finding a reliable clinic, one offering treatments based on the rigorous science required in a clinical trial sanctioned by the US Food and Drug Administration (FDA). That’s one of the reasons why the California Institute for Regenerative Medicine (CIRM) created the CIRM Alpha Stem Cell Clinic Network and we are delighted the clinics have now been chosen as a Core program of the American Society of Hematology (ASH) Sickle Cell Disease (SCD) Collaborative Trials Network. 

The Alpha Clinics are a network of top California medical centers that specialize in delivering stem cell clinical trials to patients. It consists of five leading medical centers throughout California: City of Hope, University of California (UC) San Diego, UC Irvine & UC Los Angeles, UC Davis and UC San Francisco.

The mission of the ASH Research Collaborative SCD Clinical Trials Network is to improve outcomes for individuals with Sickle Cell Disease by promoting innovation in therapy development and clinical trial research.

Like CIRM, the ASH Clinical Trials Network is a member of the National Heart, Lung and Blood Institute’s Cure Sickle Cell Initiative. This is a collaborative partnership to accelerate the development of genetic therapies to cure SCD within five to ten years.

“The key to finding a cure for this crippling disease, and finding it quickly, is to work together”, says Maria T. Millan, MD, President & CEO of CIRM. “That’s why we are delighted to be chosen as a core program for the ASH Sickle Cell Disease Clinical Trials Network. This partnership means we can share data and information about best practices to help us improve the quality of the research being done and the clinical care we can offer patients. We already have 23 clinical stage therapies in cell and gene therapy, including two clinical trials targeting SCD, so we feel we have a lot to bring to the partnership in terms of experience and expertise.”

Sickle Cell disease is a life-threatening blood disorder that affects 100,000 people, mostly African Americans, in the US. It is caused by a single genetic mutation that results in the production of “sickle” shaped red blood cells that can block blood vessels causing intense pain, recurrent hospitalization, multi-organ damage and strokes.    

According to Mark Walters, MD, Director of UCSF Benioff Children’s Hospital Oakland’s Blood and Marrow Transplantation program, ”the currently available drugs treat the symptoms of  sickle cell disease but are not a cure.

“We hear a lot about the moonshot for curing cancer, but a moonshot for curing sickle cell disease should also be possible. Sickle cell disease was the first genetic disease that was discovered, and wouldn’t it be great if it is also one of the first ones we can cure in everyone?”

It is hoped that creating this network of clinical trial sites across the US will better serve an historically under-served population.

  • Establishing links and educational materials across these sites can increase patient engagement and recruitment
  • Standardizing resources across the network can ensure efficiency and coordination
  • Improving the training of clinical research staff can promote patient safety and trust and increase research quality

The CIRM Alpha Clinics Network has a proven track record of creating a faster, more streamlined approach in running clinical trials. It has developed the tools and systems to simultaneously launch clinical trials at multiple sites; created model non-disclosure agreements to make it easier for clinical trial sponsors to sign up; created a system to enable one Institutional Review Board (IRB) to approve a trial to be carried out at multiple sites rather than requiring each site to have its own IRB approval; developed best practices to quickly share experience and expertise across the network; and set up a database of over 20 million Californians to improve patient recruitment.

An Executive Summary prepared for the Western States Sickle Cell Disease Clinical Trials Network said: “the ASCC provides a formidable clinical trial unit uniquely qualified to deliver the next generation of cell and gene therapy products for SCD.”

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

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.”

CIRM Board Approves New Clinical Trial for Breast Cancer Related Brain Metastases

Dr. Saul Priceman

Yesterday the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $9.28 million to Dr. Saul Priceman at City of Hope to conduct a clinical trial for the treatment of breast cancer related brain metastases, which are tumors in the brain that have spread from the original site of the breast cancer.

This award brings the total number of CIRM-funded clinical trials to 56. 

Breast cancer is the second-most common cancer in women, both in the United States (US) and worldwide.  It is estimated that over 260,000 women in the US will be diagnosed with breast cancer in 2019 and 1 out of 8 women in the US will get breast cancer at some point during her lifetime. Some types of breast cancer have a high likelihood of metastasizing to the brain.  When that happens, there are few treatment options, leading to a poor prognosis and poor quality of life. 

Dr. Priceman’s clinical trial is testing a therapy to treat brain metastases that came from breast cancers expressing high levels of a protein called HER2.   The therapy consists 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 are modified with a protein called a chimeric antigen receptor (CAR) that recognizes the tumor protein HER2.  These modified T cells (CAR-T cells) are then infused into the patient’s brain where they are expected to detect and destroy the HER2-expressing tumors in the brain.

CIRM has also funded the earlier work related to this study, which was critical in preparing the therapy for Food and Drug Administration (FDA) approval for permission to start a clinical trial in people.

“When a patient is told that their cancer has metastasized to other areas of the body, it can be devastating news,” says Maria T. Millan, M.D., the President and CEO of CIRM.  “There are few options for patients with breast cancer brain metastases.  Standard of care treatments, which include brain irradiation and chemotherapy, have associated neurotoxicity and do little to improve survival, which is typically no more than a few months.  CAR-T cell therapy is an exciting and promising approach that now offers us a more targeted approach to address this condition.”

The CIRM Board also approved investing $19.7 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.

Dr. Mark Tuszynski at the University of California San Diego (UCSD) was awarded $6.23 million to develop a therapy for spinal cord injury (SCI). Dr. Tuszynski will use human embryonic stem cells (hESCs) to create neural stem cells (NSCs) which will then be grafted at the injury site.  In preclinical studies, the NSCs have been shown to help create a kind of relay at the injury site, restoring communication between the brain and spinal cord and re-establishing muscle control and movement.

Dr. Mark Humayun at the University of Southern California (USC) was awarded $3.73 million to develop a novel therapeutic product capable of slowing the progression of age-related macular degeneration (AMD), the leading cause of vision loss in the US.

The approach that Dr. Humayun is developing will use a biologic product produced by human embryonic stem cells (hESCs). This material will be injected into the eye of patients with early development of dry AMD, supporting the survival of photoreceptors in the affected retina, the kind of cells damaged by the disease.

The TRAN1 awards went to:

Stay tuned for our next blog which will dive into each of these awards in much more detail.

CIRM public events highlight uncertain future of stem cell research

When governments cut funding for scientific research the consequences can be swift, and painful. In Canada last week for example, the government of Ontario cut $5 million in annual funding for stem cell research, effectively ending a project developing a therapy to heal the damaged lungs of premature babies.

Here in the US the federal government is already placing restrictions on support for fetal tissue research and there is speculation embryonic stem cell research could be next. That’s why agencies like CIRM are so important. We don’t rely on a government giving us money every year. Instead, thanks to the voters of California, we have had a steady supply of funds to enable us to plan long-term and support multi-year projects.

But those funds are due to run out soon. We anticipate funding our last new awards this year and while we have enough money to continue supporting all the projects our Board has already approved, we won’t be able to take on any new projects. That’s bad news for the scientists and, ultimately, really bad for the patients who are in need of new treatments for currently incurable diseases.

We are going to talk about that in two upcoming events.

UC San Diego Sanford Stem Cell Clinical Center

The first is a patient advocate event at UC San Diego on Tuesday, May 28th from 12.30pm to 1.30pm. It’s free, there is parking and snacks and refreshments will be available.

This will feature UC San Diego’s Dr. Catriona Jamieson, CIRM’s President and CEO Dr. Maria Millan and CIRM Board member and Patient Advocate for Parkinson’s Disease, David Higgins PhD. The three will talk about the exciting progress being made at UC San Diego and other programs around California, but also the uncertain future and the impact that could have for the field as a whole.

Here’s a link to an Eventbrite page that has more information about the event and also a link to allow you to RSVP ahead of time.

For all of you who don’t live in the San Diego Area – or who do but can’t make it to the event – we are holding a similar discussion online on a special Facebook Live: Ask the Stem Cell Team About the Future of Stem Cell Research event on Thursday, May 30th from noon till 1pm PDT.

This also features Dr. Millan and Dr. Higgins, but it also features UC Davis stem cell scientist, CIRM-grantee and renowned blogger Paul Knoepfler PhD.

Each brings their own experience, expertise and perspective on the field and will discuss the impact that a reduction in funding for stem cell research would have, not just in the short term but in the long run.

Because we all have a stake in what happens, both events – whether it’s in person or online – include time for questions from you, the audience.

You can find our Facebook Live: Ask the Stem Cell Team About the Future of Stem Cell Research on our Facebook page at noon on May 30th PDT

Advancing stem cell research in many ways

Speakers at the Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

From Day One CIRM’s goal has been to advance stem cell research in California. We don’t do that just by funding the most promising research -though the 51 clinical trials we have funded to date clearly shows we do that rather well – but also by trying to bring the best minds in the field together to overcome problems.

Over the years we have held conferences, workshops and symposiums on everything from Parkinson’s disease, cerebral palsy and tissue engineering. Each one attracted the key players and stakeholders in the field, brainstorming ideas to get past obstacles and to explore new ways of developing therapies. It’s an attempt to get scientists, who would normally be rivals or competitors, to collaborate and partner together in finding the best way forward.

It’s not easy to do, and the results are not always obvious right away, but it is essential if we hope to live up to our mission of accelerating stem cell therapies to patients with unmet medical needs.

For example. This past week we helped organize two big events and were participants in another.

The first event we pulled together, in partnership with Cedars-Sinai Medical Center, was a workshop called “Brainstorm Neurodegeneration”. It brought together leaders in stem cell research, genomics, big data, patient advocacy and the Food and Drug Administration (FDA) to tackle some of the issues that have hampered progress in finding treatments for things like Parkinson’s, Alzheimer’s, ALS and Huntington’s disease.

We rather ambitiously subtitled the workshop “a cutting-edge meeting to disrupt the field” and while the two days of discussions didn’t resolve all the problems facing us it did produce some fascinating ideas and some tantalizing glimpses at ways to advance the field.

Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

Two days later we partnered with UC San Francisco to host the Fourth Annual CIRM Alpha Stem Cell Clinics Network Symposium. This brought together the scientists who develop therapies, the doctors and nurses who deliver them, and the patients who are in need of them. The theme was “The Past, Present & Future of Regenerative Medicine” and included both a look at the initial discoveries in gene therapy that led us to where we are now as well as a look to the future when cellular therapies, we believe, will become a routine option for patients. 

Bringing these different groups together is important for us. We feel each has a key role to play in moving these projects and out of the lab and into clinical trials and that it is only by working together that they can succeed in producing the treatments and cures patients so desperately need.

Cierra Jackson: Photo by Marco Sanchez

As always it was the patients who surprised us. One, Cierra Danielle Jackson, talked about what it was like to be cured of her sickle cell disease. I think it’s fair to say that most in the audience expected Cierra to talk about her delight at no longer having the crippling and life-threatening condition. And she did. But she also talked about how hard it was adjusting to this new reality.

Cierra said sickle cell disease had been a part of her life for all her life, it shaped her daily life and her relationships with her family and many others. So, to suddenly have that no longer be a part of her caused a kind of identity crisis. Who was she now that she was no longer someone with sickle cell disease?

She talked about how people with most diseases were normal before they got sick, and will be normal after they are cured. But for people with sickle cell, being sick is all they have known. That was their normal. And now they have to adjust to a new normal.

It was a powerful reminder to everyone that in developing new treatments we have to consider the whole person, their psychological and emotional sides as well as the physical.

CIRM’s Dr. Maria Millan (right) at a panel presentation at the Stanford Drug Discovery Symposium. Panel from left to right are: James Doroshow, NCI; Sandy Weill, former CEO Citigroup; Allan Jones, CEO Allen Institute

And so on to the third event we were part of, the Stanford Drug Discovery Symposium. This was a high level, invitation-only scientific meeting that included some heavy hitters – such as Nobel Prize winners Paul Berg and  Randy Schekman, former FDA Commissioner Robert Califf. Over the course of two days they examined the role that philanthropy plays in advancing research, the increasingly important role of immunotherapy in battling diseases like cancer and how tools such as artificial intelligence and big data are shaping the future.

CIRM’s President and CEO, Dr. Maria Millan, was one of those invited to speak and she talked about how California’s investment in stem cell research is delivering Something Better than Hope – which by a happy coincidence is the title of our 2018 Annual Report. She highlighted some of the 51 clinical trials we have funded, and the lives that have been changed and saved by this research.

The presentations at these conferences and workshops are important, but so too are the conversations that happen outside the auditorium, over lunch or at coffee. Many great collaborations have happened when scientists get a chance to share ideas, or when researchers talk to patients about their ideas for a successful clinical trial.

It’s amazing what happens when you bring people together who might otherwise never have met. The ideas they come up with can change the world.

Mending Stem Cells: The Past, Present and Future of Regenerative Medicine

To Mend: (verb used with object) to make (something broken, worn, torn or otherwise damaged) whole, sound or usable by repairing.

It’s remarkable to believe, but today doctors literally have the tools to repair damaged cells. These tools are being used to treat people with diseases that were once incurable. The field of regenerative medicine has made tremendous progress in the last 15 years, but how did these tools come about and what is the experience of patients being treated with them?

These questions, and hopefully yours too, are going to be answered at the fourth annual CIRM Alpha Stem Cell Clinics Symposium on April 18, 2019 at the University of California at San Francisco.

UCSF Mission Bay Campus

The symposium is free, and the program is designed with patients and the public in mind, so don’t be shy and put your scientific thinking caps on! A complete agenda may be found here

Perhaps one of the most remarkable discoveries in the past decade are new tools that enable doctors to “edit” or correct a patient’s own DNA. DNA correction tools came about because of a remarkable string of scientific breakthroughs. The symposium will dive into this history and discuss  how these tools are being used today to treat patients.

One specific example of the promise that DNA editing holds is for those with sickle cell disease (SCD), a condition where patients’ blood forming stem cells contain a genetic error that causes the disease. The symposium will describe how the CIRM Alpha Stem Cell Clinics Network, a series of medical centers across California whose focus is on stem cell clinical trials, are supporting work aimed at mending blood cells to cure debilitating diseases like SCD.

Doctors, nurses and patients involved with these trials will be telling their stories and describing their experiences. One important focus will be how Alpha Clinic teams are partnering with community members to ensure that patients, interested in new treatments, are informed about the availability of clinical trials and receive sufficient information to make the best treatment choices.

The fourth annual CIRM Alpha Stem Cell Clinics Symposium is an opportunity for patients, their families and the public to meet the pioneers who are literally mending a patients own stem cells to cure their disease.

For registration information go here.


Rare Disease Gets Big Boost from California’s Stem Cell Agency

UC Irvine’s Dr. Leslie Thompson and patient advocate Frances Saldana after the CIRM Board vote to approve funding for Huntington’s disease

If you were looking for a poster child for an unmet medical need Huntington’s disease (HD) would be high on the list. It’s a devastating disease that attacks the brain, steadily destroying the ability to control body movement and speech. It impairs thinking and often leads to dementia. It’s always fatal and there are no treatments that can stop or reverse the course of the disease. Today the Board of the California Institute for Regenerative Medicine (CIRM) voted to support a project that shows promise in changing that.

The Board voted to approve $6 million to enable Dr. Leslie Thompson and her team at the University of California, Irvine to do the late stage testing needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people. The therapy involves transplanting stem cells that have been turned into neural stem cells which secrete a molecule called brain-derived neurotrophic factor (BDNF), which has been shown to promote the growth and improve the function of brain cells. The goal is to slow down the progression of this debilitating disease.

“Huntington’s disease affects around 30,000 people in the US and children born to parents with HD have a 50/50 chance of getting the disease themselves,” says Dr. Maria T. Millan, the President and CEO of CIRM. “We have supported Dr. Thompson’s work for a number of years, reflecting our commitment to helping the best science advance, and are hopeful today’s vote will take it a crucial step closer to a clinical trial.”

Another project supported by CIRM at an earlier stage of research was also given funding for a clinical trial.

The Board approved almost $12 million to support a clinical trial to help people undergoing a kidney transplant. Right now, there are around 100,000 people in the US waiting to get a kidney transplant. Even those fortunate enough to get one face a lifetime on immunosuppressive drugs to stop the body rejecting the new organ, drugs that increase the risk for infection, heart disease and diabetes.  

Dr. Everett Meyer, and his team at Stanford University, will use a combination of healthy donor stem cells and the patient’s own regulatory T cells (Tregs), to train the patient’s immune system to accept the transplanted kidney and eliminate the need for immunosuppressive drugs.

The initial group targeted in this clinical trial are people with what are called HLA-mismatched kidneys. This is where the donor and recipient do not share the same human leukocyte antigens (HLAs), proteins located on the surface of immune cells and other cells in the body. Around 50 percent of patients with HLA-mismatched transplants experience rejection of the organ.

In his application Dr. Meyer said they have a simple goal: “The goal is “one kidney for life” off drugs with safety for all patients. The overall health status of patients off immunosuppressive drugs will improve due to reduction in side effects associated with these drugs, and due to reduced graft loss afforded by tolerance induction that will prevent chronic rejection.”

Stem Cell Agency Board Approves 50th Clinical Trial

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Rich Lajara, the first patient treated in a CIRM-funded clinical trial

May 4th, 2011 marked a landmark moment for the California Institute for Regenerative Medicine (CIRM). On that day the Stem Cell Agency’s Board voted to invest in its first ever clinical trial, which was also the first clinical trial to use cells derived from embryonic stem cells. Today the Stem Cell Agency reached another landmark, with the Board voting to approve its 50th clinical trial.

“We have come a long way in the past seven and a half years, helping advance the field from its early days to a much more mature space today, one capable of producing new treatments and even cures,” says Jonathan Thomas, JD, PhD, Chair of the CIRM Board. “But we feel that in many ways we are just getting started, and we intend funding as many additional clinical trials as we can for as long as we can.”

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The project approved today awards almost $6.2 million to Angiocrine Bioscience Inc. to see if genetically engineered cells, derived from cord blood, can help alleviate or accelerate recovery from the toxic side effects of chemotherapy for people undergoing treatment for lymphoma and other aggressive cancers of the blood or lymph system.

“This is a project that CIRM has supported from an earlier stage of research, highlighting our commitment to moving the most promising research out of the lab and into people,” says Maria T. Millan, MD, President & CEO of CIRM. “Lymphoma is the most common blood cancer and the 6th most commonly diagnosed cancer in California. Despite advances in therapy many patients still suffer severe complications from the chemotherapy, so any treatment that can reduce those complications can not only improve quality of life but also, we hope, improve long term health outcomes for patients.”

The first clinical trial CIRM funded was with Geron, targeting spinal cord injury. While Geron halted the trial for business reasons (and returned the money, with interest) the mantle was later picked up by Asterias Biotherapeutics, which has now treated 25 patients with no serious side effects and some encouraging results.

Rich Lajara was part of the Geron trial, the first patient ever treated in a CIRM-funded clinical trial. He came to the CIRM Board meeting to tell his story saying when he was injured “I knew immediately I was paralyzed. I thought this was the end, little did I know this was just the beginning. I call it being in the wrong place at the right time.”

When he learned about the Geron clinical trial he asked how many people had been treated with stem cells. “Close to none” he was told. Nonetheless he went ahead with it. He says he has never regretted that decision, knowing it helped inform the research that has since helped others.

Since that first trial the Stem Cell Agency has funded a wide range of projects targeting heart disease and stroke, cancer, diabetes, HIV/AIDS and several rare diseases. You can see the full list on the Clinical Trials Dashboard page on our website.

Rich ended by saying: “CIRM has proven how much can be achieved if we invest in cutting-edge medical research. As most of you here probably know, CIRM’s funding from Proposition 71 is about to run out. If I had just one message I wanted people to leave with today it would be this, I will do everything I can to make sure the agency gets refunded and I hope that all of you will join me in that fight. I’m excited for the world of stem cells, particularly in California and can’t wait to see what’s on the horizon.”

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The CIRM Board also took time today to honor Dr. Bert Lubin, who is stepping down after serving almost eight years on the Board.

When he joined the Board in February, 2011 Dr. Lubin said: “I hope to use my position on this committee to advocate for stem cell research that translates into benefits for children and adults, not only in California but throughout the world.”

Over the years he certainly lived up to that goal. As a CIRM Board member he has supported research for a broad range of unmet medical needs, and specifically for curative treatments for children born with a rare life-threatening conditions such as Sickle Cell Disease and Severe Combined Immunodeficiency (SCID) as well as  treatments to help people battling vision destroying diseases.

As the President & CEO of Children’s Hospital Oakland (now UCSF Benioff Children’s Hospital Oakland) Dr. Lubin was a leader in helping advance research into new treatments for sickle cell disease and addressing health disparities in diseases such as asthma, diabetes and obesity.

Senator Art Torres said he has known Dr. Lubin since the 1970’s and in all that time has been impressed by his devotion to patients, and his humility, and that all Californians should be grateful to him for his service, and his leadership.

Dr. Lubin said he was “Really grateful to be on the Board and I consider it an honor to be part of a group that benefits patients.”

He said he may be stepping down from the CIRM Board but that was all: “I am going to retire the word retirement. I think it’s a mistake to stop doing work that you find stimulating. I’m going to repurpose the rest of my life, and work to make sure the treatments we’ve helped develop are available to everyone. I am so proud to be part of this. I am stepping down, but I am devoted to doing all I can to ensure that you get the resources you need to sustain this work for the future.”