Under her leadership, CIRM has generated a robust and growing portfolio as a patient-centric funder, partner, accelerator, and de-risker for over 1,000 projects in basic, translational, and clinical research, as well as infrastructure and education programs.
In addition to highlighting her achievements at CIRM, Dr. Millan also shared some of her personal background with the publication.
“I immigrated to the U.S. from the Philippines at 6 years old with my younger siblings one year after my mother, accompanied by my father, was recruited as a nurse to New York City,” she said. “I honed down my English watching ‘Sesame Street’ and the ‘Electric Company.’”
When asked about the biggest obstacle facing women leaders, Dr. Millan said, “Work-life balance, learning that ‘good’ is enough in certain circumstances to achieve ‘great,’ and embracing what makes us unique — our experiences as women and as mothers and to leveraging those skills to leadership roles.”
Congratulations to Dr. Millan and this year’s winners! To see the full list of award recipients, click here.
The use of antiretroviral drugs has turned HIV/AIDS from a fatal disease to one that can, in many cases in the US, be controlled. But these drugs are not a cure. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) voted to approve investing $6.85 million in a therapy that aims to cure the disease.
This is the 82nd clinical trial funded by CIRM.
There are approximately 38 million people worldwide living with HIV/AIDS. And each year there are an estimated 1.5 million new cases. The vast majority of those living with HIV do not have access to the life-saving antiretroviral medications that can keep the virus under control. People who do have access to the medications face long-term complications from them including heart disease, bone, liver and kidney problems, and changes in metabolism.
The antiretroviral medications are effective at reducing the viral load in people with HIV, but they don’t eliminate it. That’s because the virus that causes AIDS can integrate its DNA into long-living cells in the body and remain dormant. When people stop taking their medications the virus is able to rekindle and spread throughout the body.
Dr. William Kennedy and the team at Excision Bio Therapeutics have developed a therapeutic candidate called EBT-101. This is the first clinical study using the CRISPR-based platform for genome editing and excision of the latent form of HIV-1, the most common form of the virus that causes AIDS in the US and Europe. The goal is to eliminate or sufficiently reduce the hidden reservoirs of virus in the body to the point where the individual is effectively cured.
“To date only a handful of people have been cured of HIV/AIDS, so this proposal of using gene editing to eliminate the virus could be transformative,” says Dr. Maria Millan, President and CEO of CIRM. “In California alone there are almost 140,000 people living with HIV. HIV infection continues to disproportionately impact marginalized populations, many of whom are unable to access the medications that keep the virus under control. A functional cure for HIV would have an enormous impact on these communities, and others around the world.”
In a news release announcing they had dosed the first patient, Daniel Dornbusch, CEO of Excision, called it a landmark moment. “It is the first time a CRISPR-based therapy targeting an infectious disease has been administered to a patient and is expected to enable the first ever clinical assessment of a multiplexed, in vivo gene editing approach. We were able to reach this watershed moment thanks to years of innovative work by leading scientists and physicians, to whom we are immensely grateful. With this achievement, Excision has taken a major step forward in developing a one-time treatment that could transform the HIV pandemic by freeing affected people from life-long disease management and the stigma of disease.”
The Excision Bio Therapeutics team also scored high on their plan for Diversity, Equity and Inclusion. Reviewers praised them for adding on a partnering organization to provide commitments to serve underserved populations, and to engaging a community advisory board to help guide their patient recruitment.
Venous skin ulcers are open sores on the legs that can take weeks, sometimes even years, to heal and that can cause serious complications if not treated. Around 1% of Americans have venous skin ulcers. They are usually caused by insufficient blood flow from the veins of the legs back to the heart. The resulting increased blood pressure and swelling in the legs can cause an open wound to form that is painful and difficult to heal, seriously impacting quality of life. Those most at risk of developing venous leg ulcers are older people, women and non-white populations.
There are no drugs approved by the US Food and Drug Administration (FDA) for this condition and sometimes these ulcers can lead to serious skin and bone infections and, in rare cases, even skin cancer.
In a news release from UCLA, Dr. Ribas describes how his team were testing a drug called vemurafenib on patients with melanoma. Vemurafenib falls into a category of targeted cancer drugs called BRAF inhibitors, which can shrink or slow the growth of metastatic melanoma in people whose tumors have a mutation to the BRAF gene.
“We noticed that in the first two months of taking this BRAF inhibitor, patients would begin showing a thickening or overgrowth of the skin. It was somewhat of a paradox – the drug stopped the growth of skin cancer cells with the BRAF mutation, but it stimulated the growth of healthy skin cells.”
That’s when the team realized that the drug’s skin stimulating effect could be put to good use for a whole other group of patients – those with chronic wounds.
“Aside from a few famous cases, discovering a side effect that becomes a therapeutic isn’t that common,” Ribas said. “For this reason, I had to work hard to convince somebody in my lab to follow my crazy idea and take time away from immunotherapy research and do wound healing experiments.”
Thanks to that “crazy idea” Dr. Ribas and his team are now testing a gel called LUT017 that stimulates skin stem cells to proliferate and produce more keratinocytes, a kind of cell essential for repairing skin and accelerating wound healing.
The CLIN1 grant of $5,005,126 will help them manufacture and test LUT017 in pre-clinical models and apply to the FDA for permission to study it in a clinical trial in people.
Maria T. Millan, CIRM’s President and CEO says “This program adds to CIRM’s diverse portfolio of regenerative medicine approaches to tackle chronic, debilitating that lead to downstream complications, hospitalization, and a poor quality of life.”
It’s hard to get somewhere if you don’t know where you are going. Without a map you can’t plan a route to your destination. That’s why the CIRM Board approved a new Strategic Plan laying out a roadmap for the Stem Cell Agency for the next five years.
The plan builds on the achievements of Proposition 71, the voter approved ballot initiative that created the Agency in 2004, including:
Supporting 76 clinical trials.
Helping cure more than 40 children born with a rare, fatal immune disorder.
Creating the Alpha Clinics Network that specializes in the delivery of stem cell therapies to patients.
Training over 3000 students and scholars to become the future workforce of regenerative medicine.
Stimulating California’s economy with $10.7 Billion in additional sales revenue and the creation of 56,000 new jobs (between 2004-2018)
The passage of Proposition 14 in 2020 has positioned CIRM to continue to accelerate research from discovery to clinical; to drive innovative, real-world solutions resulting in transformative treatments for patients; and to ensure the affordability and accessibility of those treatments to a diverse community of patients in an equitable manner, including those often overlooked or underrepresented in the past.
“We achieved a lot in the last 15 years and this provides a solid foundation for our strategy to bring us to the new era of CIRM and to deliver the full potential of regenerative medicine, says Dr. Maria T. Millan, the President and CEO of CIRM. “This plan lays out a roadmap for us to overcome the challenges in developing transformative therapies and making them accessible and affordable in an equitable fashion to a diverse California. The plan will guide us in that work through the development of novel scientific endeavors, effective healthcare delivery models, and expanded education and training programs.”
The Strategic Plan is organized into three main themes:
Advance World Class Science – Foster a culture of collaborative science by creating knowledge networks and shared research tools and technologies that encourage and facilitate data and resource sharing.
Deliver Real World Solutions – Accelerate approval of therapies by optimizing our support models for CIRM-funded clinical trials with attention to including underserved communities; build the California Manufacturing Network to overcome manufacturing hurdles; and expand the Alpha Clinics network and create the Community Care Centers of Excellence to deliver therapies to a diverse patient population often in underserved communities.
Provide Opportunity for All – Build a racially, ethnically and experientially diverse and highly skilled workforce to support the growing regenerative medicine economy in California; deliver a roadmap for access and affordability of regenerative medicine for all California patients.
Reflecting these goals, CIRM’s new mission statement is: Accelerating world class science to deliver transformative regenerative medicine treatments in an equitable manner to a diverse California and world.
“We realize that these are ambitious goals but they are achievable,” says Dr. Millan, “If CIRM is going to continue to be a global leader in the field of regenerative medicine, and to live up to the faith shown in us by the people of California, we believe we have to aim high. We have a terrific team, a clear vision and a determination to fulfill our mission. And that’s what we intend to do.”
Hematologic malignancies are cancers that affect the blood, bone marrow and lymph nodes and include different forms of leukemia and lymphoma. Current treatments can be effective, but in those patients that do not respond, there are few treatment options. Today, the governing Board of the California Institute for Regenerative Medicine (CIRM) approved investing $4.1 million in a therapy aimed at helping patients who have failed standard therapy.
Dr. Ezra Cohen, at the University of California San Diego, and Oncternal Therapeutics are targeting a protein called ROR1 that is found in B cell malignancies, such as leukemias and lymphomas, and solid tumors such as breast, lung and colon. They are using a molecule called a chimeric antigen receptor (CAR) that can enable a patient’s own T cells, an important part of the immune system, to target and kill their cancer cells. These cells are derived from a related approach with an antibody therapy that targets ROR1-binding medication called Cirmtuzumab, also created with CIRM support. This CAR-T product is designed to recognize and kill cancer stem cells that express ROR1.
This is a late-stage preclinical project so the goal is to show they can produce enough high-quality cells to treat patients, as well as complete other regulatory measures needed for them to apply to the US Food and Drug Administration (FDA) for permission to test the therapy in a clinical trial in people.
If given the go-ahead by the FDA the therapy will target patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and acute lymphoblastic leukemia (ALL).
“CAR-T cell therapies represent a transformational advance in the treatment of hematologic malignancies,” says Dr. Maria T. Millan, CIRM’s President and CEO. “This approach addresses the need to develop new therapies for patients whose cancers are resistant to standard chemotherapies, who have few therapeutic options and a very poor chance or recovery.”
Yesterday the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $8.39 million to the University of California, San Francisco (UCSF) to fund a clinical trial for sickle cell disease (SCD). An additional $51.08 million was awarded to fifteen community colleges and universities across California to fund undergraduate and master’s level programs that will help train the next generation of stem cell researchers.
SCD is an inherited blood disorder caused by a single gene mutation that changes a single base in the B globin gene leading to the production of defective hemoglobin that polymerizes and damages red blood cells thus the “sickle” shaped red blood cells. The damaged cells cause blood vessels to occlude/close up and that can lead to multiple organ damage as well as reduced quality of life and life expectancy.
Mark Walters, M.D., and his team at UCSF Benioff Children’s Hospital Oakland will be conducting a clinical trial that uses CRISPR-Cas9 gene editing technology to correct the genetic mutation in the blood stem cells of patients with severe SCD. The corrected blood stem cells will then be reintroduced back into patients with the goal of correcting the defective hemoglobin and thus producing functional, normal shaped red blood cells.
This clinical trial will be eligible for co-funding under the landmark agreement between CIRM and the National Heart, Lung, and Blood Institute (NHLBI) of the NIH. The CIRM-NHLBI agreement is intended to co-fund cell and gene therapy programs under the NHLBI’s “Cure Sickle Cell” initiative. The goal is to markedly accelerate the development of cell and gene therapies for SCD. CIRM has previously funded the preclinical development of this therapy through a Translational award as well as its IND-enabling studies through a Late Stage Preclinical award in partnership with NHLBI.
The CIRM Bridges to Stem Cell Research and Therapy program provides undergraduate and master’s students with the opportunity to take stem cell related courses and receive hands on experience and training in a stem cell research related laboratory at a university or biotechnology company. Fifteen institutions received a total of $51.08 million to carry out these programs to train the next generation of scientists.
The awards are summarized in the table below.
Bridges to Stem Cell Research and Therapy at Pasadena City College
Pasadena City College
CIRM Bridges to Stem Cell Research and Therapy Training Grant
CSU San Marcos
Bridges to Stem Cell Research Internship Program
San Diego State University
CIRM Bridges 3.0
CIRM Regenerative Medicine and Stem Cell Research Biotechnology Training Program
CSU Long Beach
Stem Cell Internships in Laboratory-based Learning (SCILL) continue to expand the scientific workforce for stem cells research and therapies.
San Jose State University
Strengthening the Pipeline of Master’s-level Scientific and Laboratory Personnel in Stem Cell Research
CIRM Bridges Science Master’s Program
San Francisco State University
CIRM Graduate Student Training in Stem Cell Sciences in the Stem Cell Technology and Lab Management Emphasis of the MS Biotechnology Program
CSU Channel Islands
CSUN CIRM Bridges 3.0 Stem Cell Research & Therapy Training Program
Stem Cell Scholars: a workforce development pipeline, educating, training and engaging students from basic research to clinical translation.
CSU San Bernardino
Training Master’s Students to Advance the Regenerative Medicine Field
Cal Poly San Luis Obispo
Building Career Pathways into Stem Cell Research and Therapy Development
City College of San Francisco
Bridges to Stem Cell Research and Therapy: A Talent Development Program for Training Diverse Undergraduates for Careers in Regenerative Medicine
CIRM Bridges to Stem Cell Research and Therapy
Berkeley City College
“We are pleased to fund a promising trial for sickle cell disease that uses the Nobel Prize winning gene editing technology CRISPR-Cas9,” says Maria T. Millan, M.D., President and CEO of CIRM. “This clinical trial is a testament to how the CIRM model supports promising early-stage research, accelerates it through translational development, and advances it into the clinics. As the field advances, we must also meet the demand for promising young scientists. The CIRM Bridges programs across the state of California will provide students with the tools and resources to begin their careers in regenerative medicine.”
This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $11.99 million to Cedars-Sinai to fund a clinical trial for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.
ALS is a neurodegenerative disease that results in the death of nerve cells in the brain and spinal cord, causing the muscles in the body to gradually weaken, leading to loss of limb function, difficulty breathing, paralysis, and eventually death. There are medications that can slow down the progression of ALS, but unfortunately there is no cure for the disease.
Clive Svendsen, Ph.D., executive director of Cedars-Sinai’s Board of Governors Regenerative Medicine Institute, and his team will be conducting a trial that uses a combined cell and gene therapy approach as a treatment for ALS. The trial builds upon the Stem Cell Agency’s first ALS trial, also conducted by Cedars-Sinai and Svendsen.
Genetically engineered stem cells will be transplanted into the motor cortex, an area of the brain responsible for voluntary movements. These transplanted cells then become astrocytes, a type of support cell that help keep nerve cells functioning. The astrocytes have been genetically altered to deliver high doses of a growth factor which has been shown to protect nerve cells. The goal of this approach is to protect the upper motor neurons controlling muscle function and meaningfully improve the quality of life for ALS patients.
“ALS is a devastating disease that attacks the spinal cord and brain and results in the progressive loss of the ability to move, to swallow and eventually to breathe. ” says Maria T. Millan, M.D., President and CEO of CIRM. “This clinical trial builds on Dr. Svendsen’s work previously funded by CIRM. We are fortunate to be able to support this important work, which was made possible by California citizens who voted to reauthorize CIRM under Proposition 14 this past November.”
Brain Neurotherapy Bio, Inc. (BNB) is pleased to announce the treatment of the first patient in its Parkinson’s gene therapy study. The CIRM-funded study, led by Dr. Krystof Bankiewicz, is one of the 64 clinical trials funded by the California state agency to date.
Parkinson’s is a neurodegenerative movement disorder that affects one million people in the U.S alone and leads to shaking, stiffness, and problems with walking, balance, and coordination. It is caused by the breakdown and death of dopaminergic neurons, special nerve cells in the brain responsible for the production of dopamine, a chemical messenger that is crucial for normal brain activity.
The patient was treated at The Ohio State University Wexner Medical Center with a gene therapy designed 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 treatment seeks to increase dopamine production in the brain, alleviating Parkinson’s symptoms and potentially slowing down the disease progress.
“We are pleased to support this multi-institution California collaboration with Ohio State to take a novel first-in-human gene therapy into a clinical trial for Parkinson’s Disease.” says Maria T. Millan, M.D., President and CEO of CIRM. “This is the culmination of years of scientific research by the Bankiewicz team to improve upon previous attempts to translate the potential therapeutic effect of GDNF to the neurons damaged in the disease. We join the Parkinson’s community in following the outcome of this vital research opportunity.”
CIRM Board Member and patient advocate David Higgins, Ph.D. is also excited about this latest development. For Dr. Higgins, advocating for Parkinson’s is a very personal journey since he, his grandmother, and his uncle were diagnosed with the disease.
“Our best chance for developing better treatments for Parkinson’s is to test as many logical approaches as possible. CIRM encourages out-of-the-box thinking by providing funding for novel approaches. The Parkinson’s community is a-buzz with excitement about the GDNF approach and looks to CIRM to identify, fund, and promote these kinds of programs.”
In a news release Dr. Sandra Kostyk, director of the Movement Disorders Division at Ohio State Wexner Medical Center said this approach involves infusing a gene therapy solution deep into a part of the brain affected by Parkinson’s: “This is a onetime treatment strategy that could have ongoing lifelong benefits. Though it’s hoped that this treatment will slow disease progression, we don’t expect this strategy to completely stop or cure all aspects of the disease. We’re cautiously optimistic as this research effort moves forward.”
Other trial sites located in California that are currently recruiting patients are the University of California, Irvine (UCI) and the University of California, San Francisco (UCSF). Specifically, the Irvine trial site is using the UCI Alpha Stem Cell Clinic, one of five leading medical centers throughout California that make up the CIRM Alpha Stem Cell Clinic (ASSC) Network. The ASSC Network specializes in the delivery of stem cell therapies by providing world-class, state of the art infrastructure to support clinical research.
For more information on the trial and enrollment eligibility, you can directly contact the study coordinators by email at the trial sites listed:
Today the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $750,000 to Dr. Xiaokui Zhang at Celularity to conduct a clinical trial for the treatment of COVID-19. This brings the total number of CIRM clinical trials to 64, including three targeting the coronavirus.
This trial will use blood stem cells obtained from the placenta to generate natural killer (NK) cells, a type of white blood cell that is a vital part of the immune system, and administer them to patients with COVID-19. NK cells play an important role in defense against cancer and in fighting off viral infections. The goal is to administer these cells to locate the active sites of COVID-19 infection and destroy the virus-infected cells. These NK cells have been used in two other clinical trials for acute myeloid leukemia and multiple myeloma.
The Board also approved two additional awards for Discovery Stage Research (DISC2), which promote promising new technologies that could be translated to enable broad use and improve patient care.
One award for $100,000 was given to Dr. Albert Wong at Stanford. Dr. Wong has recently received an award from CIRM to develop a vaccine that produces a CD8+ T cell response to boost the body’s immune response to remove COVID-19 infected cells. The current award will enable him to expand on the initial approach to increase its potential to impact the Latinx and African American populations, two ethnicities that are disproportionately impacted by the virus in California.
The other award was for $249,996 and was given to Dr. Preet Chaudhary at the University of Southern California. Dr. Chaudary will use induced pluripotent stem cells (iPSCs) to generate natural killer cells (NK). These NK cells will express a chimeric antigen receptor (CAR), a synthetic receptor that will directly target the immune cells to kill cells infected with the virus. The ultimate goal is for these iPSC-NK-CAR cells to be used as a treatment for COVID-19.
“These programs address the role of the body’s immune T and NK cells in combatting viral infection and CIRM is fortunate enough to be able to assist these investigators in applying experience and knowledge gained elsewhere to find targeted treatments for COVID-19” says Dr. Maria T. Millan, the President & CEO of CIRM. “This type of critical thinking reflects the resourcefulness of researchers when evaluating their scientific tool kits. Projects like these align with CIRM’s track record of supporting research at different stages and for different diseases than the original target.”
The CIRM Board voted to endorse a new initiative to refund the agency and provide it with $5.5 billion to continue its work. The ‘California Stem Cell Research, Treatments and Cures Initiative of 2020 will appear on the November ballot.
The Board also approved a resolution honoring Ken Burtis, PhD., for his long service on the Board. Dr. Burtis was honored for his almost four decades of service at UC Davis as a student, professor and administrator and for his 11 years on the CIRM Board as both a member and alternate member. In the resolution marking his retirement the Board praised him, saying “his experience, commitment, knowledge, and leadership, contributed greatly to the momentum of discovery and the future therapies which will be the ultimate outcome of the dedicated work of the researchers receiving CIRM funding.”
Jonathan Thomas, the Chair of the Board, said “Ken has been invaluable and I’ve always found him to have tremendous insight. He has served as a great source of advice and inspiration to me and to the ICOC in dealing with all the topics we have had to face.”
Lauren Miller Rogen thanked Dr. Burtis, saying “I sat next to you at my first meeting and was feeling so extraordinarily overwhelmed and you went out of your way to explain all these big science words to me. You were always a source of help and support, and you explained things to me in a way that I always appreciated with my normal brain.”
Dr. Burtis said it has been a real honor and privilege to be on the Board. “I’ve been amazed and astounded at the passion and dedication that the Board and CIRM staff have brought to this work. Every meeting over the years there has been a moment of drama and then resolution and this Board always manages to reach agreement and serve the people of California.”
The COVID-19 virus targets many different parts of the body, often with deadly or life-threatening consequences. This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved investments in three early-stage research programs taking different approaches to battling the virus.
Dr. Jianhua Yu at the Beckman Research Institute of City of Hope was awarded $150,000 to use stem cells from umbilical cord blood to attack the virus. Dr. Yu and his team have many years of experience in taking cord blood cells and turning them into what are called chimeric antigen receptor (CAR) natural killer (NK) cells. The goal is to deploy these CAR NK cells to specifically target cells infected with COVID-19. This leverages the body of work at the City of Hope to develop this technology for cancer.
Dr. Helen Blau of Stanford University was awarded $149,996 to target recovery of muscle stem cells of the diaphragm in COVID-19 patients who have an extended period on a ventilator.
Patients with severe coronavirus often suffer respiratory failure and end up on mechanical ventilation that takes over the work of breathing. Over time, the diaphragm, the main muscle responsible for inhaling and exhaling, weakens and atrophies. There is no treatment for this kind of localized muscle wasting and it is anticipated that some of these patients will take months, if not years, to fully recover. Dr. Blau’s team proposes to develop a therapy with Prostaglandin E2 and Bupivacaine based on data generated by Dr. Blau’s group that these drugs, already approved by the FDA for other indications, have the potential to stimulate muscle stem cell recovery.
Dr. Albert Wong, also from Stanford University, was awarded $149,999 to develop vaccine candidates against COVID-19.
Most vaccine candidates are focused on getting the body to produce an antibody response to block the virus. However, Dr. Wong thinks that to be truly effective, a vaccine also needs to produce a CD8+ T cell response to augment an effective immune response to remove the COVID-19 infected cells that are hijacked by the virus to spread and cause illness. This team will use the experience it gained using CIRM funds to vaccine against glioblastoma, a deadly brain cancer, to advance a similar approach to produce an effective cellular immune response to combat COVID-19.
“CIRM is committed to supporting novel, multi-pronged approaches to battle this COVID-19 crisis that leverage solid science and knowledge gained in other areas.” says Dr. Maria T. Millan, the President & CEO of CIRM. “These three projects highlight three very different approaches to combatting the acute devastating health manifestations of COVID-19 as well as the debilitating sequelae that impact the ability to recover from the acute illness. Through this COVID funding opportunity, CIRM is enabling researchers to re-direct work they have already done, often with CIRM support, to quickly develop new approaches to COVID-19.”