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

2018-12-13 01.18.50Rich Lajara

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.”

angiocrinelogo

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.”

lubinbert-mug

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.”

Promising Approach to Curing Spina Bifida Gets $5.6 Million from Stem Cell Agency

300px-Spina-bifida

Every day in the U.S. four children are born with spina bifida. It is the most common cause of lifelong paralysis and also frequently leads to other serious health problems affecting the bowel and bladder. The impact on families is enormous. A new approach to repairing the defect that causes spina bifida was today awarded $5.66 million by the Board of the California Institute for Regenerative Medicine (CIRM).

In spina bifida the spinal cord doesn’t form properly, in many cases leaving a section of it open, exposing tissues and nerves. The current standard of care is surgery, but even this leaves almost 60% of children unable to walk independently. Diana Farmer MD, and Aijun Wang PhD at U.C. Davis will use mesenchymal stem cells, taken from a donor placenta, and place them on a form of synthetic scaffold over the injury site in the womb. Tests in animals show this approach was able to repair the defect and prevent paralysis.

“Spina bifida is a devastating condition for babies born with this disorder and the families who care for them,” says Maria T. Millan, MD, President & CEO of CIRM. “CIRM has funded this important work from its earliest stages and we are committed to working with Dr. Farmer’s team to moving this work to the stage where it can be tested in patients.”

The CLIN1 award will provide funding to enable the UC Davis team to do the final testing and preparations needed to apply to the FDA for permission to start a clinical trial.

Dr. Farmer says she and Dr. Wang, have been working on this approach for more than ten years and are excited about being able to take the next step.

“There were many times of frustration, many times when cell types we explored and worked with didn’t work,” says Dr. Farmer. “But it’s the patients, seeing them, talking to them and working with them, that keeps me motivated to do the science, to keep persevering.”

If this therapy is successful it will have a huge economic impact on California, and on the rest of the world. Because spina bifida is a lifelong condition involving many operations, many stays in the hospital and, in some cases, lifelong use of a wheelchair this has a huge financial, and psychological, burden on the family.

“It affects them in so many ways; parents having to miss work or take time off work to care for their child, other children in the family feeling neglected because their brother or sister needs so much attention,” says Dr. Farmer. “That’s why we are so grateful to CIRM. Because this is a rare disease and finding funding for those is hard. CIRM has been a perfect partner in helping bring this approach, blending stem cell therapy and tissue engineering, together to help these families.”

This video shows English bulldogs treated with this approach who are now able to walk:

Stem Cell Agency Invests in New Immunotherapy Approach to HIV, Plus Promising Projects Targeting Blindness and Leukemia

HIV AIDS

While we have made great progress in developing therapies that control the AIDS virus, HIV/AIDS remains a chronic condition and HIV medicines themselves can give rise to a new set of medical issues. That’s why the Board of the California Institute for Regenerative Medicine (CIRM) has awarded $3.8 million to a team from City of Hope to develop an HIV immunotherapy.

The City of Hope team, led by Xiuli Wang, is developing a chimeric antigen receptor T cell or CAR-T that will enable them to target and kill HIV Infection. These CAR-T cells are designed to respond to a vaccine to expand on demand to battle residual HIV as required.

Jeff Sheehy

CIRM Board member Jeff Sheehy

Jeff Sheehy, a CIRM Board member and patient advocate for HIV/AIDS, says there is a real need for a new approach.

“With 37 million people worldwide living with HIV, including one million Americans, a single treatment that cures is desperately needed.  An exciting feature of this approach is the way it is combined with the cytomegalovirus (CMV) vaccine. Making CAR T therapies safer and more efficient would not only help produce a new HIV treatment but would help with CAR T cancer therapies and could facilitate CAR T therapies for other diseases.”

This is a late stage pre-clinical program with a goal of developing the cell therapy and getting the data needed to apply to the Food and Drug Administration (FDA) for permission to start a clinical trial.

The Board also approved three projects under its Translation Research Program, this is promising research that is building on basic scientific studies to hopefully create new therapies.

  • $5.068 million to University of California at Los Angeles’ Steven Schwartz to use a patient’s own adult cells to develop a treatment for diseases of the retina that can lead to blindness
  • $4.17 million to Karin Gaensler at the University of California at San Francisco to use a leukemia patient’s own cells to develop a vaccine that will stimulate their immune system to attack and destroy leukemia stem cells
  • Almost $4.24 million to Stanford’s Ted Leng to develop an off-the-shelf treatment for age-related macular degeneration (AMD), the leading cause of vision loss in the elderly.

The Board also approved funding for seven projects in the Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Application Title Institution CIRM Committed Funding
DISC2-10979 Universal Pluripotent Liver Failure Therapy (UPLiFT)

 

Children’s Hospital of Los Angeles $1,297,512

 

DISC2-11105 Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer

 

Stanford $1,415,016
DISC2-10973 Small Molecule Proteostasis Regulators to Treat Photoreceptor Diseases

 

U.C. San Diego $1,160,648
DISC2-11070 Drug Development for Autism Spectrum Disorder Using Human Patient iPSCs

 

Scripps $1,827,576
DISC2-11183 A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs

 

University of Southern California $833,971
DISC2-11199 Modulation of the Wnt pathway to restore inner ear function

 

Stanford $1,394,870
DISC2-11109 Regenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion Syndrome

 

Stanford $1,415,016

Finally, the Board approved the Agency’s 2019 research budget. Given CIRM’s new partnership with the National Heart, Lung, Blood Institute (NHLBI) to accelerate promising therapies that could help people with Sickle Cell Disease (SCD) the Agency is proposing to set aside $30 million in funding for this program.

barbara_lee_official_photo

Congresswoman Barbara Lee (D-CA 13th District)

“I am deeply grateful for organizations like CIRM and NHLBI that do vital work every day to help people struggling with Sickle Cell Disease,” said Congresswoman Barbara Lee (D-CA 13th District). “As a member of the House Appropriations Subcommittee on Labor, Health and Human Services, and Education, I know well the importance of this work. This innovative partnership between CIRM and NHLBI is an encouraging sign of progress, and I applaud both organizations for their tireless work to cure Sickle Cell Disease.”

Under the agreement CIRM and the NHLBI will coordinate efforts to identify and co-fund promising therapies targeting SCD.  Programs that are ready to start an IND-enabling or clinical trial project for sickle cell can apply to CIRM for funding from both agencies. CIRM will share application information with the NHLBI and CIRM’s Grants Working Group (GWG) – an independent panel of experts which reviews the scientific merits of applications – will review the applications and make recommendations. The NHLBI will then quickly decide if it wants to partner with CIRM on co-funding the project and if the CIRM governing Board approves the project for funding, the two organizations will agree on a cost-sharing partnership for the clinical trial. CIRM will then set the milestones and manage the single CIRM award and all monitoring of the project.

“This is an extraordinary opportunity to create a first-of-its-kind partnership with the NHLBI to accelerate the development of curative cell and gene treatments for patients suffering with Sickle Cell Disease” says Maria T. Millan, MD, President & CEO of CIRM. “This allows us to multiply the impact each dollar has to find relief for children and adults who battle with this life-threatening, disabling condition that results in a dramatically shortened lifespan.  We are pleased to be able to leverage CIRM’s acceleration model, expertise and infrastructure to partner with the NHLBI to find a cure for this condition that afflicts 100,000 Americans and millions around the globe.”

The budget for 2019 is:

Program type 2019
CLIN1 & 2

CLIN1& 2 Sickle Cell Disease

$93 million

$30 million

TRANSLATIONAL $20 million
DISCOVER $0
EDUCATION $600K

 

 

Maria Millan Opens Up About the Current State of CIRM

In an article published to the SF Chronicle last week, reporter Erin Allday and Joaquin Palomino discussed CIRM, and how our work as an agency has paid off since our inception in 2004.

The article, which is a part of a four part series, explores the hope and reality of the revolutionary science of stem cell therapy. It focuses on what has transpired since 2004, when California voters approved a $3 billion bond measure to fund stem cell research with the promise that it soon would produce new treatments for incurable diseases.

In four parts, it follows the stories of patients desperately seeking remedies; probes the for-profit clinics where unproven and unregulated treatments are being offered; takes you into the labs and hospital rooms where scientists are testing new therapies; and provides a comprehensive accounting of what California’s multi billion dollar bet on stem cells has achieved.

Our CEO Maria Millan shared her thoughts in response to some of the questions raised by this article.

Q: There have been many critics who say it’s taking too long for CIRM to deliver cures, and they expected more. What is your response to these people?

A: Many of us can relate that relief cannot come quickly enough for our relatives and friends who suffer from debilitating and devastating medical conditions— I believe that is why many of us are at CIRM, an organization whose mission is to accelerate stem cell treatments to patients with unmet medical needs. Through the years, we have enabled the creation of an incredible ecosystem of top scientists and researchers and partnered with patients and patient advocates to pursue this mission.  We continually strive to improve and to become more efficient  and we share the sense of urgency to harness the potential of stem cell biology to deliver relief to those in need.

Q: Given all of the differences between CIRM and the NIH, why do you think the reporter compared CIRM to the NIH?

A: The NIH is the largest health research funder world-wide, has been around a lot longer, has a much larger budget >$30B this past year alone and the NHLBI alone has a $3B annual budget—NHLBI is just one of the 27 NIH Institutes. The reason that CIRM was formed is that the advocates of Proposition 71 wanted to make sure that scientists and developers can pursue vital research opportunities that may not have access to funding by traditional funders, including the NIH. CIRM has a total budget of $3B available to fund research and support operations and we have been managing that budget since the passage of Proposition 71 in 2004.  If we consider  the number of stem cell trials for given available budget, CIRM has funded a disproportionately higher number of translational and clinical programs in stem cell and regenerative medicine. In fact, the NHLBI has entered into a collaboration with CIRM on their Cure Sickle Cell initiative because of CIRM’s specialization in funding and enabling cell-gene regenerative medicine research.  I take this as a validation of CIRM’s value proposition in this new area– acceleration, translation, and clinical trials.

Q: Given the visibility being given to stem cell tourism and direct to consumer marketing of unproven and unregulated therapies, what value does CIRM bring to patients?

A: CIRM is positioned as the trusted agency for delivering on high quality trials, for being on the side of patients for safe trials and treatments and is a credible partner for patient, industry, government stakeholders to tackle this issue of stem cell tourism. We only fund clinical trials backed by solid scientific data with FDA permission to test it in patients. We have funded research being conducted at top tier medical centers and created the Alpha Stem Cell Clinic Network to provide people with high quality clinical trials. We are remaining in close contact with our legislators, including Speaker Pro Tem Kevin Mullin, Chair of the Assembly Select Committee on Biotechnology, to evaluate potential ways to protect patients from illegitimate clinics while progress is being made with legitimate approaches.

Q: Do you feel that enough money is being put towards basic research?

A: If we had the budget to do so, we would like to be able to fund more discovery research as well as translational and clinical research.  However, approximately $880M CIRM funds have gone into basic research thus far.  CIRM has a specialized and very unique role that supports and fosters rigorous stem cell and regenerative medicine science but, CIRM has distinguished itself as an agency that specializes in accelerating the translation of this science to therapies for patients.

Dr. Millan also appeared with SF Chronicle reporter Erin Allday and UC Davis stem cell scientist Paul Knoepfler on a Facebook Live talk about the work of the stem cell agency.

Research Targeting Prostate Cancer Gets Almost $4 Million Support from CIRM

Prostate cancer

A program hoping to supercharge a patient’s own immune system cells to attack and kill a treatment resistant form of prostate cancer was today awarded $3.99 million by the governing Board of the California Institute for Regenerative Medicine (CIRM)

In the U.S., prostate cancer is the second most common cause of cancer deaths in men.  An estimated 170,000 new cases are diagnosed each year and over 29,000 deaths are estimated in 2018.  Early stage prostate cancer is usually managed by surgery, radiation and/or hormone therapy. However, for men diagnosed with castrate-resistant metastatic prostate cancer (CRPC) these treatments often fail to work and the disease eventually proves fatal.

Poseida Therapeutics will be funded by CIRM to develop genetically engineered chimeric antigen receptor T cells (CAR-T) to treat metastatic CRPC. In cancer, there is a breakdown in the natural ability of immune T-cells to survey the body and recognize, bind to and kill cancerous cells. Poseida is engineering T cells and T memory stem cells to express a chimeric antigen receptor that arms these cells to more efficiently target, bind to and destroy the cancer cell. Millions of these cells are then grown in the laboratory and then re-infused into the patient. The CAR-T memory stem cells have the potential to persist long-term and kill residual cancer calls.

“This is a promising approach to an incurable disease where patients have few options,” says Maria T. Millan, M.D., President and CEO of CIRM. “The use of chimeric antigen receptor engineered T cells has led to impressive results in blood malignancies and a natural extension of this promising approach is to tackle currently untreatable solid malignancies, such as castrate resistant metastatic prostate cancer. CIRM is pleased to partner on this program and to add it to its portfolio that involves CAR T memory stem cells.”

Poseida Therapeutics plans to use the funding to complete the late-stage testing needed to apply to the Food and Drug Administration for the go-ahead to start a clinical trial in people.

Quest Awards

The CIRM Board also voted to approve investing $10 million for eight projects under its Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Among those approved for funding are:

  • Eric Adler at UC San Diego is using genetically modified blood stem cells to treat Danon Disease, a rare and fatal condition that affects the heart
  • Li Gan at the Gladstone Institutes will use induced pluripotent stem cells to develop a therapy for a familial form of dementia
  • Saul Priceman at City of Hope will use CAR-T therapy to develop a treatment for recurrent ovarian cancer

Because the amount of funding for the recommended applications exceeded the money set aside, the Application Subcommittee voted to approve partial funding for two projects, DISC2-11192 and DISC2-11109 and to recommend, at the next full Board meeting in October, that the projects get the remainder of the funds needed to complete their research.

The successful applications are:

 

APPLICATION

 

TITLE

 

INSTITUTION

CIRM COMMITTED FUNDING
DISC2-11131 Genetically Modified Hematopoietic Stem Cells for the

Treatment of Danon Disease

 

 

U.C San Diego

 

$1,393,200

 

DISC2-11157 Preclinical Development of An HSC-Engineered Off-

The-Shelf iNKT Cell Therapy for Cancer

 

 

U.C. Los Angeles

 

$1,404,000

DISC2-11036 Non-viral reprogramming of the endogenous TCRα

locus to direct stem memory T cells against shared

neoantigens in malignant gliomas

 

 

U.C. San Francisco

 

$900,000

DISC2-11175 Therapeutic immune tolerant human islet-like

organoids (HILOs) for Type 1 Diabetes

 

 

Salk Institute

 

$1,637,209

DISC2-11107 Chimeric Antigen Receptor-Engineered Stem/Memory

T Cells for the Treatment of Recurrent Ovarian Cancer

 

 

City of Hope

 

$1,381,104

DISC2-11165 Develop iPSC-derived microglia to treat progranulin-

deficient Frontotemporal Dementia

 

 

Gladstone Institutes

 

$1,553,923

DISC2-11192 Mesenchymal stem cell extracellular vesicles as

therapy for pulmonary fibrosis

 

 

U.C. San Diego

 

$865,282

DISC2-11109 Regenerative Thymic Tissues as Curative Cell

Therapy for Patients with 22q11 Deletion Syndrome

 

 

Stanford University

 

$865,282

 

 

CIRM invests in stem cell clinical trial targeting lung cancer and promising research into osteoporosis and incontinence

Lung cancer

Lung cancer: Photo courtesy Verywell

The five-year survival rate for people diagnosed with the most advanced stage of non-small cell lung cancer (NSCLC) is pretty grim, only between one and 10 percent. To address this devastating condition, the Board of the California Institute for Regenerative Medicine (CIRM) today voted to invest almost $12 million in a team from UCLA that is pioneering a combination therapy for NSCLC.

The team is using the patient’s own immune system where their dendritic cells – key cells in our immune system – are genetically modified to boost their ability to stimulate their native T cells – a type of white blood cell – to destroy cancer cells.  The investigators will combine this cell therapy with the FDA-approved therapy pembrolizumab (better known as Keytruda) a therapeutic that renders cancer cells more susceptible to clearance by the immune system.

“Lung cancer is a leading cause of cancer death for men and women, leading to 150,000 deaths each year and there is clearly a need for new and more effective treatments,” says Maria T. Millan, M.D., the President and CEO of CIRM. “We are pleased to support this program that is exploring a combination immunotherapy with gene modified cell and antibody for one of the most extreme forms of lung cancer.”

Translation Awards

The CIRM Board also approved investing $14.15 million in four projects under its Translation Research Program. The goal of these awards is to support promising stem cell research and help it move out of the laboratory and into clinical trials in people.

Researchers at Stanford were awarded almost $6 million to help develop a treatment for urinary incontinence (UI). Despite being one of the most common indications for surgery in women, one third of elderly women continue to suffer from debilitating urinary incontinence because they are not candidates for surgery or because surgery fails to address their condition.

The Stanford team is developing an approach using the patient’s own cells to create smooth muscle cells that can replace those lost in UI. If this approach is successful, it provides a proof of concept for replacement of smooth muscle cells that could potentially address other conditions in the urinary tract and in the digestive tract.

Max BioPharma Inc. was awarded almost $1.7 million to test a therapy that targets stem cells in the skeleton, creating new bone forming cells and blocking the destruction of bone cells caused by osteoporosis.

In its application the company stressed the benefit this could have for California’s diverse population stating: “Our program has the potential to have a significant positive impact on the lives of patients with osteoporosis, especially in California where its unique demographics make it particularly vulnerable. Latinos are 31% more likely to have osteoporosis than Caucasians, and California has the largest Latino population in the US, accounting for 39% of its population.”

Application Title Institution CIRM funding
TRAN1-10958 Autologous iPSC-derived smooth muscle cell therapy for treatment of urinary incontinence

 

 

Stanford University

 

$5,977,155

 

TRAN2-10990 Development of a noninvasive prenatal test for beta-hemoglobinopathies for earlier stem cell therapeutic interventions

 

 

Children’s Hospital Oakland Research Institute

 

$1,721,606

 

TRAN1-10937 Therapeutic development of an oxysterol with bone anabolic and anti-resorptive properties for intervention in osteoporosis  

MAX BioPharma Inc.

 

$1,689,855

 

TRAN1-10995 Morphological and functional integration of stem cell derived retina organoid sheets into degenerating retina models

 

 

UC Irvine

 

$4,769,039