It is estimated that as many as 90 percent of people in industrialized countries who die every day, die from diseases of aging such as heart disease, stroke, and cancer. Of those still alive the numbers aren’t much more reassuring. More than 80 percent of people over the age of 65 have a chronic medical condition, while 68 percent have two or more.
Current medications can help keep some of those conditions, such as high blood pressure, under control but regenerative medicine wants to do a lot more than that. We want to turn back the clock and restore function to damaged organs and tissues and limbs. That research is already underway and we are inviting you to a public event to hear all about that work and the promise it holds.
On June 16th from 3p – 4.30p PST we are holding a panel discussion exploring the impact of regenerative medicine on aging. We’ll hear from experts on heart disease and stroke; we will look at other ground breaking research into aging; and we’ll discuss the vital role patients and patient advocates play in helping advance this work.
The discussion is taking place in San Francisco at the annual conference of the International Society for Stem Cell Research. But you can watch it from the comfort of your own home. That’s because we are going to live stream the event.
While there have been some encouraging advances in treating cancer in recent decades, there are still many cancers that either resist treatment or recur after treatment. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved investing in a therapy targeting some of these hard-to-treat tumors.
BioEclipse Therapeutics Inc. was awarded nearly $8M to test a therapy using immune cells loaded with a cancer-killing virus that targets cancer tissue but spares healthy tissue.
BioEclipse combines two approaches—an immune cell called a cytokine-induced killer (CIK) cell and a virus engineered to kill cancer cells called an oncolytic virus (OV)—to create what they call “a multi-mechanistic, targeted treatment.”
They will use the patient’s own immune cells and, in the lab, combine them with the OV. The cell/virus combination will then be administered back to the patient. The job of the CIK cells is to carry the virus to the tumors. The virus is designed to specifically attack and kill tumors and stimulate the patient’s immune system to attack the tumor cells. The goal is to eradicate the primary tumor and prevent relapse and recurrence.
“With the intent to develop this treatment for chemotherapy-resistant or refractory solid tumors—including colorectal cancer, triple negative breast cancer, ovarian cancer, gastric cancer, hepatocellular carcinoma, and osteosarcoma—it addresses a significant unmet medical need in fatal conditions for which there are limited treatment options,” says Dr. Maria T. Millan, President and CEO of CIRM.
The CIRM Board also approved more than $18 million in funding four projects under the Translation Projects program. The goal of this program is to support promising regenerative medicine (stem cell-based or gene therapy) projects that accelerate completion of translational stage activities necessary for advancement to clinical study or broad end use.
The awards went to:
Application
Title
Institution
Award Amount
TRAN1-133442
Optogenetic therapy for treating retinitis pigmentosa and other inherited retinal diseases
Paul Bresge Ray Therapeutics Inc.
$3,999,553
TRAN3-13332
Living Synthetic Vascular Grafts with Renewable Endothelium
Aijun Wang UC Davis
$3,112,567
TRAN1-13370
Next generation affinity-tuned CAR for prostate cancer
Preet Chaudhary University of Southern California
$5,805,144
TRAN1-3345
Autologous MPO Knock-Out Hematopoietic Stem and Progenitor Cells for Pulmonary Arterial Hypertension
Dr. Antoni Ribas in his research lab on the UCLA Campus: Photo courtesy Ann Johansson
When UCLA’s Dr. Antoni Ribas was researching a potential therapy for melanoma, a form of skin cancer, he stumbled upon something unexpected. That unexpected discovery has now resulted in him getting a $5 million dollar award from the the governing Board of the California Institute for Regenerative Medicine (CIRM) to develop a therapy to accelerate wound healing in legs.
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.”
Dr. Turbeville has almost 20 years of experience in Medical Affairs, creating strategies and teams for biopharma and digital healthcare companies. He has experience supporting the development of therapies in cancer, neurology, metabolic and genetic disorders and in working with Regulatory Authorities such as the Food and Drug Administration, EMA and others.
Sean has a PhD in Epidemiology from the University of Oklahoma Health Sciences Center where he later taught courses as an Adjunct Associate Professor. He is the owner of two global regulatory resources for biopharma, “The Global Regulatory Framework for Medical Information in the Pharmaceutical Industry” and “The Global Guide to Compassionate Use Programs”. Before joining CIRM, Dr. Turbeville was the President of Matanzas Group, a Medical Affairs consultancy providing a range of Medical Affairs services to over 20 small, growing biopharmaceutical companies.
CIRM’s Vice Chair, Sen. (ret) Art Torres says Dr. Turbeville is a great addition to the team: “Sean’s expertise will be invaluable to our working group and to our coordination with the Governor and Legislature on affordability and accessibility issues affecting patients.”
“I am honored to work at CIRM, where science, business, regulatory and policy work together to accelerate world class science and provide Californians equal accessibility to novel therapies,” says Dr. Turbeville. “It’s a unique opportunity to give back to the state that has given me and my family so much.”
The VP of Medical Affairs and Policy is a new position and Dr. Turbeville will have responsibility for overseeing a Medical Affairs Team that will work with the CIRM team, the Accessibility and Affordability Working Group and the board to develop healthcare policy, reimbursement strategy, post-market activities and research. He will also oversee and develop CIRM’s infrastructure programs for clinical trials and the delivery of therapies, in particular the Alpha Clinics Network and the future Community Care Centers of Excellence.
“As CIRM drives more transformative regenerative therapies to the clinics, we set a bold strategic goal to deliver a roadmap for access and affordability of these treatments to all patient communities. We are extremely excited to have Sean as a qualified leader and expert in the field to lead this charge,” says Maria Millan, CIRM’s President and CEO. “He has been a mission-driven patient advocate and board member of the Cholangiocarcinoma Foundation which he joined after losing his father. In this role, he drove the creation of alliances with companies to increase access to clinical trials for patients with this devastating cancer.”
Dr. Turbeville joins the growing ranks of new team members that CIRM has hired since the passage of Proposition 14 in November 2020. CIRM is rebuilding and expanding its team to meet new challenges and advance the mission of the agency.
Among the new hires is Linda Nevin, PhD, who joined us as a Senior Science Officer on the Review and Portfolio Development Team. Linda is a former Associate Editor for the journal PLOS Medicine and brings detailed experience with data sharing, health equity research, large cohort studies, and machine learning in medicine.Linda got her PhD in Neuroscience from UCSF and has a BS/MS in Biological Sciences from Stanford.
Katie Sharify is the new Communications Team Coordinator, but she has a long history of involvement with CIRM. More than ten years ago Katie was a patient in the first clinical trial CIRM funded, a stem cell therapy aimed at helping people with spinal cord injuries. Since then, Katie has been a tireless supporter and advocate on behalf of CIRM, so we were delighted to be able to make her a full-time member of the team.
Maziar Shah Mohammed, PhD, a Senior Science Officer in our Scientific Programs group, has undergraduate and master’s degrees in Materials Science and Engineering and he got his PhD in Biomaterials and Tissue Engineering from McGill University in Canada. He comes to CIRM with experience in academic research, the medical device industry and, most recently as a Lead Reviewer at the U.S. Food and Drug Administration (FDA) in the Center for Devices and Radiological Health (CDRH).
Lisa McGinley, PhD, joined CIRM as a Senior Science Officer in Therapeutics and Development. She has expertise in stem cell therapy discovery, development and translation in cardiovascular and neurology spaces. She received her PhD in Regenerative Medicine from the National University of Ireland, Galway and completed her postdoctoral fellowship in Bioengineering at the Georgia Institute of Technology. Most recently she was an Assistant Professor in Neurology at the University of Michigan, where she led an NIH-funded collaborative stem cell initiative developing therapeutics for ALS and Alzheimer’s disease.
Treecy Truc Nguyen is CIRM’s new Project Manager in the Therapeutics Development group. Treecy got her BSHS and MPH from Massachusetts College of Pharmacy and Health Sciences. Before joining CIRM she was the Senior Systems Manager at The Unity Council, a non-profit community development organization committed to social equality and improving the quality of life in traditionally underserved communities.
The new team members are:
Claudette Mandac Project Manager, Review
Mitra Hooshmand SSO, Special Projects and Strategic Initiatives
Vanessa Singh HR Manager
Pouneh Simpson Director of Finance
Alexandra Caraballo Grants Management Specialist
Kevin Marks General Counsel
Michael Bunch Business Services Officer
Rosa Canet-Aviles Vice President, Science
Uta Grieshammer SSO, Science
Linda Nevin SSO, Review and Portfolio
Stephanie Bautista Executive Assistant to the President
It’s hard to think of something as being rare when it affects up to 30 million Americans and 300 million people worldwide. But the truth is there are more than 6,000 conditions – those affecting 200,000 people or fewer – that are considered rare.
Today, February 28th, is Rare Disease Day. It’s a day to remind ourselves of the millions of people, and their families, struggling with these diseases. These conditions are also called or orphan diseases because, in many cases, drug companies were not interested in adopting them to develop treatments.
At the California Institute for Regenerative Medicine (CIRM), we have no such reservations. In fact last Friday our governing Board voted to invest almost $12 million to support a clinical trial for IPEX syndrome. IPEX syndrome is a condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. This leads to the development of Type 1 diabetes, severe eczema, damage to the small intestines and kidneys and failure to thrive. It’s diagnosed in infancy, most of those affected are boys, and it is often fatal.
Taylor Lookofsky (who has IPEX syndrome) and his father Brian
IPEX is one of two dozen rare diseases that CIRM is funding a clinical trial for. In fact, more than one third of all the projects we fund target a rare disease or condition. Those include:
Some might question the wisdom of investing hundreds of millions of dollars in conditions that affect a relatively small number of patients. But if you see the faces of these patients and get to know their families, as we do, you know that often agencies like CIRM are their only hope.
Dr. Maria Millan, CIRM’s President and CEO, says the benefits of one successful approach can often extend far beyond one rare disease.
“Children with IPEX syndrome clearly represent a group of patients with an unmet medical need, and this therapy could make a huge difference in their lives. Success of this treatment in this rare disease presents far-reaching potential to develop treatments for a larger number of patients with a broad array of immune disorders.”
CIRM is proud to fund and spread awareness of rare diseases and invites you to watch this video about how they affect families around the world.
Taylor Lookofsky (center), a person with IPEX syndrome, with his father Brian and Dr. Rosa Bacchetta
IPEX syndrome is a rare condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. The syndrome mostly affects boys, is diagnosed in the first year of life and is often fatal. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) invested almost $12 million in a therapy being tested in a clinical trial to help these patients.
Children born with IPEX syndrome have abnormalities in the FOXP3 gene. This gene controls the production of a type of immune cell called a T Regulatory or Treg cell. Without a normal FOXP3 +Treg cells other immune cells attack the body leading to the development of IPEX syndrome, Type 1 diabetes, severe eczema, damage to the small intestines and kidneys and failure to thrive.
Current treatments involve the use of steroids to suppress the immune system – which helps ease symptoms but doesn’t slow down the progression of the disease – or a bone marrow stem cell transplant. However, a transplant requires a healthy, closely matched donor to reduce the risk of a potentially fatal transplant complication called graft vs host disease, in which the donated immune cells attack the recipient’s tissues.
Dr. Rosa Bacchetta and her team at Stanford University have developed a therapy using the patient’s own natural CD4 T cells that, in the lab, have been genetically modified to express the FoxP3 gene and converted into Treg cells. Those cells are then re-infused into the patient with a goal of determining if this approach is both safe and beneficial. Because the cells come from the patients there will be fewer concerns about the need for immunosuppressive treatment to stop the body rejecting the cells. It will also help avoid the problems of finding a healthy donor and graft vs host disease.
Dr. Bacchetta has received approval from the Food and Drug Administration (FDA) to test this approach in a Phase 1 clinical trial for patients suffering with IPEX syndrome.
“Children with IPEX syndrome clearly represent a group of patients with an unmet medical need, and this therapy could make a huge difference in their lives,” says Dr. Maria T. Millan, the President and CEO of CIRM. “Success of this treatment in this rare disease presents far-reaching potential to develop treatments for a larger number of patients with a broad array of immune disorders resulting from dysfunctional regulatory T cells.”
In addition to a strong scientific recommendation to fund the project the review team also praised it for the applicants’ commitment to the principles of Diversity, Equity and Inclusion in their proposal. The project proposes a wide catchment area, with a strong focus on enrolling people who are low-income, uninsured or members of traditionally overlooked racial and ethnic minority communities.
When Hataalii Begay was born in a remote part of the Navajo nation he was diagnosed with a rare, usually fatal condition. Today, thanks to a therapy developed at UCSF and funded by CIRM, he’s a normal healthy four year old boy running around in cowboy boots.
That stem cell therapy could now help save the lives of other children born with this deadly immune disorder because it has been granted fast-track review status by the US Food and Drug Administration (FDA).
The disorder is Artemis-SCID, a form of severe combined immunodeficiency disease. Children born with this condition have no functioning immune system so even a simple infection can prove life-threatening or fatal.
Currently, the only approved treatment for Artemis-SCID is a bone-marrow transplant, but many children are unable to find a healthy matched donor for that procedure. Even when they do find a donor they often need regular injections of immunoglobulin to boost their immune system.
In this clinical trial, UCSF Doctors Mort Cowan and Jennifer Puck are using the patient’s own blood stem cells, taken from their bone marrow. In the lab, the cells are modified to correct the genetic mutation that causes Artemis-SCID and then re-infused back into the patients. The goal is that over the course of several months these cells will create a new blood supply, one that is free of Artemis-SCID, and that will in turn help repair the child’s immune system.
So far the team has treated ten newly-diagnosed infants and three older children who failed transplants. Dr. Cowan says early data from the trial is encouraging. “With gene therapy, we are seeing these babies getting older. They have normal T-cell immunity and are getting immunized and vaccinated. You wouldn’t know they had any sort of condition if you met them; it’s very heartening.”
Because of that encouraging data, the FDA is granting this approach Regenerative Medicine Advanced Therapy (RMAT) designation. RMAT is a fast-track designation that can help speed up the development, review and potential approval of treatments for serious or life-threatening diseases.
“This is great news for the team at UCSF and in particular for the children and families affected by Artemis-SCID,” says Dr. Maria T. Millan, the President and CEO of CIRM. “The RMAT designation means that innovative forms of cell and gene therapies like this one may be able to accelerate their route to full approval by the FDA and be available to all the patients who need it.”
CIRM Bridges student discusses her poster presentation
At CIRM, the bread and butter of what we do is funding research and hopefully advancing therapies to patients. But the jam, that’s our education programs. Helping train the next generation of stem cell and gene therapy scientists is really inspiring. Watching these young students – and some are just high school juniors – come in and grasp the science and quickly become fluent in talking about it and creating their own experiments shows the future is in good hands.
Right now we fund several programs, such as our SPARK and Bridges internships, but they can’t cover everything, so last week the CIRM Board approved a new training program called COMPASS (Creating Opportunities through Mentorship and Partnership Across Stem Cell Science). The program will fill a critical need for skilled research practitioners who understand and contribute at all levels in the translation of science to medicine, from bench to bedside.
The objective of the COMPASS Training Program is to prepare a diverse group of undergraduate students for careers in regenerative medicine through the creation of novel recruitment and support mechanisms that identify and foster untapped talent within populations that are historically under-represented in the biomedical sciences. It will combine hands-on research with mentorship experiences to enhance transition of students to successful careers. A parallel objective is to foster greater awareness and appreciation of diversity, equity and inclusion in trainees, mentors, and other program participants
The CIRM Board approved investing $58.22 million for up to 20 applications for a five-year duration.
“This new program highlights our growing commitment to creating a diverse workforce, one that taps into communities that have been historically under-represented in the biomedical sciences,” says Dr. Maria T. Millan, President and CEO of CIRM. “The COVID19 pandemic made it clear that the benefits of scientific discovery are not always accessible to communities that most need them. CIRM is committed to tackling these challenges by creating a diverse and dedicated workforce that can meet the technical demands of taking novel treatment ideas and making them a reality.”
The Board also approved a new $80 million concept plan to expand the CIRM Alpha Stem Cell Clinic Network. The Network clinics are all in top California medical centers that have the experience and the expertise to deliver high-quality FDA-authorized stem cell clinical trials to patients.
There are currently five Alpha Clinics – UC San Diego; UCLA/UC Irvine; City of Hope; UCSF; UC Davis – and since 2015 they have hosted more than 105 clinical trials, enrolled more than 750 patients in these trials, and generated more than $95 million in industry contracts.
Each award will provide up to $8 million in funding over a five-year period. The clinics will have to include:
A demonstrated ability to offer stem cell and gene therapies to patients as part of a clinical trial.
Programs to help support the career development of doctors, nurses, researchers or other medical professionals essential for regenerative medicine clinical trials.
A commitment to data sharing and meeting CIRM’s requirements addressing issues of diversity, equity and inclusion and meeting the needs of California’s diverse patient population.
If you want to know if a new drug or therapy is going to work in the people it affects the most you need to test the drug or therapy in the people most affected by the disease. That would seem blindingly obvious, wouldn’t it? Apparently not.
Case in point. A new asthma medication, one that seemingly shows real promise in reducing attacks in children, was tested on an almost entirely white patient population, even though Black and Puerto Rican children are far more likely to suffer from asthma.
The study enrolled more than 400 children, between the ages of 6 and 11, with moderate to serious uncontrolled asthma and treated them with a medication called Dupixent. The results, published in the New England Journal of Medicine, were impressive. Children given Dupixent had an average drop in severe asthma attacks of 65 percent compared to children given a placebo.
The only problem is 90 percent of the children in the study were white. Why is that a problem? Because, according to the Asthma and Allergy Foundation of America, only 9.5 percent of white children have asthma, compared to 24 percent of Puerto Rican children and 18 percent of Black children. So, the groups most likely to suffer from the disease were disproportionately excluded from a study about a treatment for the disease.
Some people might think, “So what! If the medication works for one kid it will work for another, what does race have to do with it?” Quite a lot actually.
A study in the Journal of Allergy and Clinical Immunology concluded that: “Race/ethnicity modified the association between total IgE (an antibody in the blood that is a marker for asthma) and asthma exacerbations. Elevated IgE level was associated with worse asthma outcomes in Puerto Ricans… Our findings suggest that eligibility for asthma biologic therapies differs across pediatric racial/ethnic populations.”
The article concluded by calling for “more studies in diverse populations for equitable treatment of minority patients with asthma.” Something that clearly didn’t happen in the Dupixent study.
While that’s more than disappointing, it’s not surprising. A recent study of vaccine clinical trials in JAMA Network Open found that:
Overall, white individuals made up almost 80 percent of people enrolled.
Black individuals were represented only 10.6 percent of the time.
Latino participants were represented just 11.6 percent of the time.
Additionally, in pediatric trials, Black participants were represented just over 10 percent of the time and Latino participants were represented 22.5 percent of the time. The study concluded by saying that “diversity enrollment targets are needed for vaccine trials in the US.”
I would expand on that, saying they are needed for all clinical trials. That’s one of the many reasons why we at the California Institute for Regenerative Medicine (CIRM) are making Diversity, Equity and Inclusion an important part of everything we do, such as requiring all applicants to have a written DEI plan if they want funding from us. Dr. Maria Millan, our President and CEO, recently co-authored an article in Nature Cell Biology, driving home the need for greater diversity in basic science and research in general.
DEI has become an important part of the conversation this past year. But the Dupixent trial shows that if we are truly serious about making it part of what we do, we have to stop talking and start acting.
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.”
The Stem Cellar 