Building Bridges to a Brighter Future – Celebrating 11 Years of Workforce Development

By: Dr. Kelly Shepard, Associate Director, Discovery and Translation, CIRM

CIRM 2020 Bridges Conference via Zoom

Every July, CIRM is thrilled to announce the arrival a new generation of stem cell scientists who are ready to hit the ground running as laboratory technicians, educators, communicators, or future leaders of their chosen profession. These diverse and remarkable individuals are the latest graduates of the CIRM Bridges Program, which provides students the opportunity to take coursework at California state schools and community colleges and conduct stem cell research at top universities and industry labs. The culmination of this experience is an annual conference where students are able to network with their peers and share their research outcomes with one another.

While the Bridges program has been operating in full force for 11 years now, 2020 brought some new challenges to everyone in the form of a global pandemic. Shelter in place orders- cancellation of in person classes- travel restrictions…. these are only a few of the factors that have touched our lives in recent months. But sometimes challenges bring opportunities and a new way of doing things. Through the collective efforts of program directors, institutional officials, mentors and students, the 2020 Bridges alumni were able to complete their training requirements at their institutions and present their research at the Annual Bridges Conference, which was conducted virtually this year. While visiting students posters via Zoom, we at CIRM were thrilled to learn that many of them already had jobs waiting for them or had been accepted into PhD or MD programs, similar to alumni from previous years, which now number over 1400.

While we cannot predict all of the twists and turns that life may bring us, we can be confident that scientific research and discovery will remain essential to creating a brighter future, and that Bridges alumni will be there to help us navigate it.

Perseverance: from theory to therapy. Our story over the last year – and a half

Some of the stars of our Annual Report

It’s been a long time coming. Eighteen months to be precise. Which is a peculiarly long time for an Annual Report. The world is certainly a very different place today than when we started, and yet our core mission hasn’t changed at all, except to spring into action to make our own contribution to fighting the coronavirus.

This latest CIRM Annual Reportcovers 2019 through June 30, 2020. Why? Well, as you probably know we are running out of money and could be funding our last new awards by the end of this year. So, we wanted to produce as complete a picture of our achievements as we could – keeping in mind that we might not be around to produce a report next year.

Dr. Catriona Jamieson, UC San Diego physician and researcher

It’s a pretty jam-packed report. It covers everything from the 14 new clinical trials we have funded this year, including three specifically focused on COVID-19. It looks at the extraordinary researchers that we fund and the progress they have made, and the billions of additional dollars our funding has helped leverage for California. But at the heart of it, and at the heart of everything we do, are the patients. They’re the reason we are here. They are the reason we do what we do.

Byron Jenkins, former Naval fighter pilot who battled back from his own fight with multiple myeloma

There are stories of people like Byron Jenkins who almost died from multiple myeloma but is now back leading a full, active life with his family thanks to a CIRM-funded therapy with Poseida. There is Jordan Janz, a young man who once depended on taking 56 pills a day to keep his rare disease, cystinosis, under control but is now hoping a stem cell therapy developed by Dr. Stephanie Cherqui and her team at UC San Diego will make that something of the past.

Jordan Janz and Dr. Stephanie Cherqui

These individuals are remarkable on so many levels, not the least because they were willing to be among the first people ever to try these therapies. They are pioneers in every sense of the word.

Sneha Santosh, former CIRM Bridges student and now a researcher with Novo Nordisk

There is a lot of information in the report, charting the work we have done over the last 18 months. But it’s also a celebration of everyone who made it possible, and our way of saying thank you to the people of California who gave us this incredible honor and opportunity to do this work.

We hope you enjoy it.

A new voice and vision added to CIRM Board

UC Davis School of Medicine Dean, Dr. Allison Brashear: Photo courtesy UCD

We have a new member on the CIRM Board – Dr. Allison Brashear is the Dean of the UC Davis School of Medicine, overseeing one of the nation’s top research, academic and medical training institutions.

Dr. Brashear is an internationally known researcher in movement disorders and an expert in ATP1A3-related diseases, a spectrum of rare neurologic disorders.

Before joining UC Davis, Dr. Brashear was professor and chair of the Department of Neurology for 14 years at Wake Forest School of Medicine.

She serves on the American Board of Psychiatry and Neurology, and has served on the boards of the American Neurological Association and the American Academy of Neurology, where she was instrumental in crafting a leadership program for women, now expanded to include leadership development for minorities.

You can read more about her background in this news release. But we wanted to get a sense of what motivates and inspires Dr. Brashear. So we asked her. And she told us.

Dean Brashear being sworn in – virtually – on the CIRM Board. Top left, James Harrision CIRM General Counsel; Jonathan Thomas, CIRM Board Chair; Dr. Brashear; and Dr. Jim Kovach, Director of Industry Alliances at UC Davis, alternative Board member.

When did you get interested in science? Was this always something you knew you wanted to do?

I loved math and science in middle school and continued with science in college. I grew up hearing my parents talk about caring for patients and the impact you could have on them and their family’s lives. My father is a pulmonologist and my mother was a Ph.D. in marriage and family therapy. Together they taught me the value of patient-centered care. 

My mother was a tremendous advocate for women. When I was in middle school she took my friend and I to the state legislature and we watched the ERA (Equal Rights Amendment) debates. It’s a powerful memory but not always flattering about what people thought at the time. So, from an early age I really became a strong advocate for women, to make sure women had opportunities and that we were an inclusive culture wherever I was. 

As a woman going into a male dominated field, how did you manage to push past the skeptics and doubters to succeed? 

Early on I recognized the need to work with senior faculty who would give me an opportunity to lead and learn.  I became a chair of neurology at Wake Forest when I was 44 and was the only woman chair for 4 years. When I was appointed to the Wake Forest Baptist Medical Center Board of Directors as one of two faculty, I was the only woman. I learned early on that it was important to have sponsorship from senior leaders to succeed. I learned that, when opportunities presented themselves, to say “yes.” This is how I became the lead investigator into ATP1A3 related diseases in 1991. That project, now 11 years funded by the NIH, is one that is led by me and three other women. 

It’s still not uncommon for me to walk into a room and be the only woman. And so, making sure that there is appropriate support for women leaders is really key.

Did you have mentors to help you along the way – what was their advice to you?

I prefer the term sponsorship. Mentors advise – which is important, but more important is the role of the sponsor. A sponsor goes out of their way to advance another career. This can be a public call-out, a well-placed phone call or giving a resident what ends up being a new pathway of research.  I appreciate the many sponsors in my life, and that includes men and women.  I aspire to be a similar sponsor. This is my way to pay it forward. 

How do you sponsor others to help them overcome barriers, etc.? 

I advise women to get extra leadership training, learn about money and to make sure to have a network of advocates. I also remind them to say thank you to those who pave the way. 

I think it goes down to the message that you meet these key people in your life and they go the extra mile to help you and you, as a leader, need to take that opportunity and really just launch from it. Along the way I found I really wanted to bring people in and grow them and that was the best part of being chair of the department and one of the reasons I wanted to be a dean. When faculty join our health system I want to set them up to succeed. Celebrating others’ success with them is a great feeling. Fostering these successes is how we can be a catalyst to research and care innovations that improve health, which is at the heart of our work.  

These are interesting times to head a major university, what advice and encouragement do you have for students just starting out who face their first year “at university” at home? 

Every change brings opportunity. University at home is hard – interpersonal relationships are so important to learning and we miss that when we are on Zoom. I advise students and faculty to nurture those social connections.

When you are not working what do you do for fun?  

I hang out with my husband and our two rescue dogs. We are making plans to go explore California when the COVID-19 pandemic settles down. We had our two adult children home during the shutdown, but both are back at school on the East Coast. 

Saying farewell to an old friend

There are some people who, when you think of them, always bring a smile to your face. Dr. Bert Lubin was one of those people. Sadly, we lost Bert to brain cancer two days ago. But the impact he had, not just as an advocate for stem cell research but as a pioneer in sickle cell disease research and a champion for children’s health, will live on.

Bert had a number of official titles but probably the one he was most proud of was President & CEO of Children’s Hospital Oakland (now UCSF Benioff Children’s Hospital Oakland). But it wasn’t the title that he cared about, it was the opportunity it gave him to make a difference in the life of children in Oakland, to create a program to find new treatments and cures for a life-threatening disease. And he has made a difference.

As I started to write this tribute to Bert, I thought about who I should ask for a quote. And then I realized I had the perfect person. Bert himself. I was fortunate enough to interview him in December 2018, when he decided to step down after eight years on the CIRM Board.  As always, he had his own positive spin on that, saying: “I don’t see myself leaving. I’m just repurposing what is my role in CIRM. I’m recycling and reinventing.”

And Bert was always full of invention.

He grew up in Bellevue, a small town outside Pittsburgh, PA. His parents ran a fruit and vegetable market there and, growing up, Bert often worked in the store. It wasn’t something he enjoyed but he said he learned some valuable lessons.

“I think what happened in my childhood is that I learned how to sell. I am a salesman. I hated working in that store, I hated it, but I liked the communication with people, they trusted me, I could sell things and they were good things. Like Christmas. I’m Jewish, we were the only Jews in that community, and at Christmas we sold Christmas trees, but the trees were sometimes crooked and they were $2.99 a tree so I convinced families that I could go to their house and set the tree so it looked straight and I helped them decorate it and they loved it.”

He said, thinking back on his life it’s almost as if there were a plan, even if he wasn’t aware of it.

“I started thinking about that more recently, I started wondering how did this even happen? I’m not a religious person but it’s almost like there’s some fate. How did I get there? It’s not that I planned it that way and it’s certainly not that my parents planned it because I was the first in my family to go to high school let alone college. My parents, when I went to medical school and then decided I wanted to spend more time in an academic direction, they were upset. They wanted me to go into practice in a community that I grew up in and be economically secure and not be on the fringe in what an academic life is like.”

And then, fate stepped in and brought him to the San Francisco Bay Area.

“What happened was, I was at the University of Pennsylvania having trained at Boston Children’s and Philadelphia Children’s, where I had started a sickle cell disease program, and was asked to look at a job in southern California to start a sickle cell program there. So, I flew to San Francisco because a lot of people I’d studied with were now working at UCSF and I thought it would be fun to see them before going down to southern California. They took me out to dinner and showed me around and I said this place is beautiful, I can play tennis out here all year round, there’s lots of music – I love jazz – and they said ‘you know Bert, have you looked at Oakland Children’s hospital? We want to start a sickle cell program center, but the patients are all in Oakland and the patient population that would be served is in Oakland. But if you came out to the Bay Area we could partner with you to start that program. 

“So, when I walked in the door here (at Oakland) and said ‘I want to create this northern California sickle cell center with UC’ the staff that was here said ‘you know we’re not a research hospital, we are a community based hospital’. I said, ‘I’m not saying you shouldn’t be that but I’m trying to create an opportunity here’ and they said to me ‘as long as you don’t ask for any money you can go and do whatever you want’.

‘They recognized that I had this fire in me to really create something that was novel. And the warmth and community commitment from this place is something that attracted me and then allowed me to build on that.

“For example, when I became the director of the research program we had $500,000 in NIH grants and when I left we had $60 million. We just grew. Why did we grow? Because we cared about the faculty and the community. We had a lovely facility, which was actually the home of the Black Panther party. It was the Black Panthers who started screening for sickle cell on street corners here in Oakland, and they were the start of the national sickle cell act so there’s a history here and I like that history.

“Then I got a sense of the opportunities that stem cell therapies would have for a variety of things, certainly including sickle cell disease, and I thought if there’s a chance to be on the CIRM Board, as an advocate for that sickle cell community, I think I’d be a good spokesperson. So, I applied. I just thought this was an exciting opportunity.

“I thought it was a natural fit for me to add some value, I only want to be on something where I think I add value.”

Bert added value to everything he did. And everyone he met felt valued by him. He was a mentor to so many people, young physicians and nurses, students starting out on their careers. And he was a friend to those in need.

He was an extraordinary man and we are grateful that we were able to call him a colleague, and a friend, for as long as we did.

When Burt stepped down from Children’s his colleagues put together this video about his life and times. It seems appropriate to share it again and remind ourselves of the gift that he was to everyone fortunate enough to know him.

CIRM Board Expands Efforts of COVID-19 Program

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) expanded efforts related to the $5 million in emergency funding for the CIRM COVID-19 program.

The new guidelines mean that inception discovery projects (DISC1), whose goal is developing new and transformational ideas, will now be eligible for CIRM COVID-19 funding.  These projects can receive up to $150,000 and must have data to confirm or reject their hypothesis within 6 months. In addition to this, quest discovery projects (DISC2), which promote the discovery of new technologies that could be translated to enable broad use, can now receive up to $250,000 in funding.

The Board approved using $1 million from the program in supplemental support for CIRM-funded COVID-19 clinical trials. Under the change an existing clinical trial can receive up to $250,000 in additional funding but must demonstrate sufficient progress and specific activities in order to be eligible.  The Board will also require that all clinical trial projects include a plan for outreach and study participation by underserved and disproportionately affected populations.

The Board also strongly encouraged those that meet the stem cell component for vaccine development for COVID-19 to apply for funding.

“We continue to receive large amounts of inquiries and applications to the COVID-19 program announcement,” said Maria T. Millan, M.D., President and CEO of CIRM. “The amendments passed by our Board today will provide additional opportunities for CIRM to support novel vaccine development, fundamental discoveries and the acceleration of clinical programs.”

CIRM Board Approves Clinical Trials Targeting COVID-19 and Sickle Cell Disease

Coronavirus particles, illustration.

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved new clinical trials for COVID-19 and sickle cell disease (SCD) and two earlier stage projects to develop therapies for COVID-19.

Dr. Michael Mathay, of the University of California at San Francisco, was awarded $750,000 for a clinical trial testing the use of Mesenchymal Stromal Cells for respiratory failure from Acute Respiratory Distress Syndrome (ARDS). In ARDS, patients’ lungs fill up with fluid and are unable to supply their body with adequate amounts of oxygen. It is a life-threatening condition and a major cause of acute respiratory failure. This will be a double-blind, randomized, placebo-controlled trial with an emphasis on treating patients from under-served communities.

This award will allow Dr. Matthay to expand his current Phase 2 trial to additional underserved communities through the UC Davis site.

“Dr. Matthay indicated in his public comments that 12 patients with COVID-related ARDS have already been enrolled in San Francisco and this funding will allow him to enroll more patients suffering from COVID- associated severe lung injury,” says Dr. Maria T. Millan, CIRM’s President & CEO. “CIRM, in addition to the NIH and the Department of Defense, has supported Dr. Matthay’s work in ARDS and this additional funding will allow him to enroll more COVID-19 patients into this Phase 2 blinded randomized controlled trial and expand the trial to 120 patients.”

The Board also approved two early stage research projects targeting COVID-19.

  • Dr. Stuart Lipton at Scripps Research Institute was awarded $150,000 to develop a drug that is both anti-viral and protects the brain against coronavirus-related damage.
  • Justin Ichida at the University of Southern California was also awarded $150,00 to determine if a drug called a kinase inhibitor can protect stem cells in the lungs, which are selectively infected and killed by the novel coronavirus.

“COVID-19 attacks so many parts of the body, including the lungs and the brain, that it is important for us to develop approaches that help protect and repair these vital organs,” says Dr. Millan. “These teams are extremely experienced and highly renowned, and we are hopeful the work they do will provide answers that will help patients battling the virus.”

The Board also awarded Dr. Pierre Caudrelier from ExcellThera $2 million to conduct a clinical trial to treat sickle cell disease patients

SCD is an inherited blood disorder caused by a single gene mutation that results in the production of “sickle” shaped red blood cells. It affects an estimated 100,000 people, mostly African American, in the US and can lead to multiple organ damage as well as reduced quality of life and life expectancy.  Although blood stem cell transplantation can cure SCD fewer than 20% of patients have access to this option due to issues with donor matching and availability.

Dr. Caudrelier is using umbilical cord stem cells from healthy donors, which could help solve the issue of matching and availability. In order to generate enough blood stem cells for transplantation, Dr. Caudrelier will be using a small molecule to expand these blood stem cells. These cells would then be transplanted into twelve children and young adults with SCD and the treatment would be monitored for safety and to see if it is helping the patients.

“CIRM is committed to finding a cure for sickle cell disease, the most common inherited blood disorder in the U.S. that results in unpredictable pain crisis, end organ damage, shortened life expectancy and financial hardship for our often-underserved black community” says Dr. Millan. “That’s why we have committed tens of millions of dollars to fund scientifically sound, innovative approaches to treat sickle cell disease. We are pleased to be able to support this cell therapy program in addition to the gene therapy approaches we are supporting in partnership with the National Heart, Lung and Blood Institute of the NIH.”

Cashing in on COVID-19

Coronavirus particles, illustration. Courtesy KTSDesign/Science Photo Library

As the coronavirus pandemic continues to spread, one of the few bright spots is how many researchers are stepping up and trying to find new ways to tackle it, to treat it and hopefully even cure it. Unfortunately, there are also those who are simply trying to cash in on it.

In the last few years the number of predatory clinics offering so-called “stem cell therapies” for everything from Alzheimer’s and multiple sclerosis to autism and arthritis has exploded in the US. The products they offer have not undergone a clinical trial to show that they work; they haven’t been approved by the US Food and Drug Administration (FDA); they don’t have any evidence they are even safe. But that doesn’t stop them marketing these claims and it isn’t stopping some of them from now trying to cash in on the fears created by the coronavirus.

One company is hawking what it calls a rapid COVID-19 test, one that can determine if you have the virus in under ten minutes (many current tests take days to produce a result). All it takes is a few drops of blood and, from the comfort of your own home, you get to find out if you are positive for COVID-19. And best of all, it claims it is 99 percent accurate.

What could be the problem with that? A lot as it turns out.

If you go to the bottom of the page on the website marketing the test it basically says “this does not work and we’re not making any claims or are in any way responsible for any results it produces.” So much for 99 percent accurate.

It’s not the only example of this kind of shameless attempt to cash in on COVID-19. So it’s appropriate that this week the Alliance for Regenerative Medicine (ARM), issued a statement strongly condemning these attempts and the clinics behind them.

ARM warns about the growing number of “stem cell clinics” (that) are taking advantage of the “hype” around stem cells – and, in certain cases, the current concern about COVID-19 – and avoiding regulation by falsely marketing illegal and potentially harmful products to patients seeking cures.” 

These so called “therapies” or tests do more than just take money – in some cases tens of thousands of dollars – from individuals: “Public health is at risk when unscrupulous providers offer stem cell products that are unapproved, unproven and fail to adhere to established rules for good manufacturing practices. Many of these providers put patients at risk by falsely marketing the benefits of treatments, and often promoting the stem cells for conditions that are outside of their area of medical expertise.”

It’s sad that even in times when so many people are working hard to find treatments for the virus, and many are risking their lives caring for those who have the virus, that there are unscrupulous people trying to make money out of it. All we can do is be mindful, be careful and be suspicious of anything that sounds too good to be true.

There are no miracle cures. No miracle treatments. No rapid blood tests you can order in the mail. Be aware. And most importantly of all, be safe.

The CIRM Board recently held a meeting to approve $5 million in emergency funding for rapid research into potential treatments for COVID-19.

An advocate’s support for CIRM’s COVID-19 funding

Patient Advocates play an important role in everything we do at the stem cell agency, helping inform all the decisions we make. So it was gratifying to hear from one of our Advocates par excellence, Adrienne Shapiro, about her support for our Board’s decision to borrow $4.2 million from our Sickle Cell Cure fund to invest in rapid research for COVID-19. The money will be repaid but it’s clear from Adrienne’s email that she thinks the Board’s action is one that stands to benefit all of us.

Adrienne Shapiro and her daughter Marissa, who has sickle cell disease

Last Friday the CIRM Board voted to borrow $4.2 million dollars from the Sickle Cell Stem Cell Cure’s budget to fund Covid-19 research. The loan will be paid back at the end of the year from funds that are returned to the CIRM budget from projects that did not use them.  At first I thought “that makes sense, if the money is not being used …” then I thought how wonderful it was that the SCD budget was there and could be used for Covid-19 research.

Wonderful because Covid-19 is a great threat to the SCD community. Sickle cell patients are at risk of dying from the virus as many have no spleens, are immune-compromised and suffer from weakened lung function due to damage from sickling red blood cells and low oxygen levels. 

Wonderful because CIRM sponsored the first large clinical stem cell trials for a cure to SCD. Their funding and commitment to finding a universal cure for SCD opened what feels like a flood gate of research for a cure and new treatments.

Wonderful because it gives CIRM an opportunity to show the world what a government organization — that is committed to tackling complex medical problems — can accomplish using efficient, inclusive, responsible and agile methodologies.

I am eager to see what happens. We all hope that new treatments and even a cure will be found soon. If it does not come from CIRM funding we know that whatever is proven using these funds will help future researchers and patients. 

After all: the SCD community is living proof that science done well leads to a world with less suffering

CIRM Board invests $5 million in emergency funding for coronavirus

Coronavirus

In response to the crisis caused by the COVID-19 virus in California and around the world the governing Board of the California Institute for Regenerative Medicine (CIRM) today held an emergency meeting to approve $5 million in rapid research funds targeting the virus.

“These are clearly extraordinary times and they require an extraordinary response from all of us,” says Dr. Maria T. Millan, President and CEO of CIRM. “Our mission is to accelerate stem cell treatments to patients with unmet medical needs. California researchers have made us aware that they are pursuing potential stem cell based approaches to the COVID-19 crisis and we felt it was our responsibility to respond by doing all we can to support this research and doing so as quickly as we possibly can.”

The Board’s decision enables CIRM to allocate $5 million in funding for peer-reviewed regenerative medicine and stem cell research that could quickly advance treatments for COVID-19. The funding will be awarded as part of an expedited approval process.

To qualify applicants would go through a full review by CIRM’s independent Grants Working Group.

  • Approved projects will be immediately forwarded to the CIRM Board for a vote
  • Projects approved by the Board would go through an accelerated contract process to ensure funds are distributed as quickly as possible

“Our hope is that we can go from application to funding within 30 to 40 days,” says Jonathan Thomas, PhD, JD, Chair of the CIRM Board. “This is a really tight timeframe, but we can’t afford to waste a moment. There is too much at stake. The coronavirus is creating an unprecedented threat to all of us and, as one of the leading players in regenerative medicine, we are committed to doing all we can to develop the tools and promote the research that will help us respond to that threat.”

Only projects that target the development or testing of a treatment for COVID-19 are eligible. They must also meet other requirements including being ready to start work within 30 days of approval and propose achieving a clear deliverable within six months. The proposed therapy must also involve a stem cell or a drug or antibody targeting stem cells.

The award amounts and duration of the award are as follows:

Award Amount and Duration Limits

Project StageSpecific ProgramAward Amount*Award Duration
Clinical trialCLIN2$750,00024 months
Late stage preclinicalCLIN1$400,00012 months
TranslationalTRAN1$350,00012 months
DiscoveryDISC2$150,00012 months

CIRM Board members were unanimous in their support for the program. Al Rowlett, the patient advocate for mental health, said: “Given the complexity of this situation and the fact that many of the individuals I represent aren’t able to advocate for themselves, I wholeheartedly support this.”

Dr. Os Steward, from UC Irvine agreed: “I think that this is a very important thing for CIRM to do for a huge number of reasons. The concept is great and CIRM is perfectly positioned to do this.”

“All hands are on deck world-wide in this fight against COVID-19.” says Dr. Millan. “CIRM will deploy its accelerated funding model to arm our stem cell researchers in this multi-pronged and global attack on the virus.”

You can learn more about the program, including how to apply, on our website.

CIRM Board Meeting Highlights Important Updates to Clinical Trials

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

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

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

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

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

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

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

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

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

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

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

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

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

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