Everything you wanted to know about COVID vaccines but never got a chance to ask

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. Today we feature a rare treat, an interview with Moderna’s Dr. Derrick Rossi.

Moderna co-founder Dr. Derrick Rossi

It’s not often you get a chance to sit down with one of the key figures in the fight against the coronavirus and get to pick his brain about the best ways to beat it. We were fortunate enough to do that on Wednesday, talking to Dr. Derrick Rossi, the co-founder of Moderna, about the vaccine his company has developed.

CIRM’s President and CEO, Dr. Maria Millan, was able to chat to Dr. Rossi for one hour about his background (he got support from CIRM in his early post-doctoral research at Stanford) and how he and his colleagues were able to develop the COVID-19 vaccine, how the vaccine works, how effective it is, how it performs against new variations of the virus.

He also told us what he would have become if this science job hadn’t worked out.

All in all it was a fascinating conversation with someone whose work is offering a sense of hope for millions of people around the world.

If you missed it first time around you can watch it here.

How a CIRM scholar helped create a life-saving COVID vaccine

Dr. Derrick Rossi might be the most famous man whose name you don’t recognize. Dr. Rossi is the co-founder of Moderna. Yes, that Moderna. The COVID-19 vaccine Moderna. The vaccine that in clinical trials proved to be around 95 percent effective against the coronavirus.

Dr. Rossi also has another claim to fame. He is a former CIRM scholar. He did some of his early research, with our support, in the lab of Stanford’s Dr. Irv Weissman.

So how do you go from a lowly post doc doing research in what, at the time, was considered a rather obscure scientific field, to creating a company that has become the focus of the hopes of millions of people around the world?  Well, join us on Wednesday, January 27th at 9am (PST) to find out.

CIRM’s President and CEO, Dr. Maria Millan, will hold a live conversation with Dr. Rossi and we want you to be part of it. You can join us to listen in, and even post questions for Dr. Rossi to answer. Think of the name dropping credentials you’ll get when say to your friends; “Well, I asked Dr. Rossi about that and he told me…..”

Being part of the conversation is as simple as clicking on this link:

After registering, you will receive a confirmation email containing information about joining the webinar.

We look forward to seeing you there.

A guide to healing

Dr. Evan Snyder

Having grown up in an era where to find your way around you had to use paper maps, a compass and a knowledge of the stars (OK, I’m not actually that old!) I’m forever grateful to whoever invented the GPS. It’s a lifesaver, and I daresay has also saved more than a few marriages!

Having a way to guide people where they need to be is amazing. Now researchers at Sanford Burnham Prebys Medical Discovery Institute have come up with a similar tool for stem cells. It’s a drug that can help guide stem cells to go where they need to go, to repair damaged tissue and improve the healing process.

In a news release Evan Snyder, MD, PhD, the senior author of the study, explained in wonderfully simply terms what they have done:

“The ability to instruct a stem cell where to go in the body or to a particular region of a given organ is the Holy Grail for regenerative medicine. Now, for the first time ever, we can direct a stem cell to a desired location and focus its therapeutic impact.”

More than a decade ago Snyder and his team discovered that when our body suffers an injury the result is often inflammation and that this then sends out signals for stem cells to come and help repair the damage. This is fine when the problem is a cut or sprain, short term issues in need of a quick fix. But what happens if it’s something more complex, such as a heart attack or stroke where the need is more long term.

In the study, funded in part by CIRM, the team took a molecule, called CXCL12, known to help guide stem cells to damaged tissue, and used it to create a drug called SDV1a. Snyder says this new drug has several key properties.

“Since inflammation can be dangerous, we modified CXCL12 by stripping away the risky bit and maximizing the good bit. Now we have a drug that draws stem cells to a region of pathology, but without creating or worsening unwanted inflammation.”

To test the drug to see how well it worked the team implanted SDV1a and some human brain stem cells into mice with Sandhoff disease, a condition that progressively destroys cells in the brain and spinal cord. They were able to demonstrate that the drug helped the stem cells migrate to where they were needed and to help in repairing the damage. The treated mice had a longer lifespan and better motor function, as well as developing symptoms later than untreated mice.

The team is now testing this drug to see if it has any impact on ALS, also known as Lou Gehrig’s disease. And Snyder says there are other areas where it could prove effective.

“We are optimistic that this drug’s mechanism of action may potentially benefit a variety of neurodegenerative disorders, as well as non-neurological conditions such as heart disease, arthritis and even brain cancer. Interestingly, because CXCL12 and its receptor are implicated in the cytokine storm that characterizes severe COVID-19, some of our insights into how to selectively inhibit inflammation without suppressing other normal processes may be useful in that arena as well.”

CIRM’s President & CEO, Dr. Maria Millan, says this kind of work highlights the important role the stem cell agency plays, in providing long-term support for promising but early stage research.

“Thanks to decades of investment in stem cell science, we are making tremendous progress in our understanding of how these cells work and how they can be harnessed to help reverse injury or disease. Dr. Snyder’s group has identified a drug that could boost the ability of neural stem cells to home to sites of injury and initiate repair. This candidate could help speed the development of stem cell treatments for conditions such as spinal cord injury and Alzheimer’s disease.”

The discovery is published in the Proceedings of the National Academy of Sciences (PNAS)

Much to be Thankful for

It’s traditional this time of year to send messages of gratitude to friends and family and colleagues. And we certainly have much to be thankful for.

Thanks to the voters of California, who passed Proposition 14, we have a bright, and busy, future. We have $5.5 billion to continue our mission of accelerating stem cell treatments to patients with unmet medical needs.

That means the pipeline of promising projects that we have supported from an early stage can now apply to us to help take that work out of the lab and into people.

It means research areas, particularly early-stage work, where we had to reduce our funding as we ran out of money can now look forward to increased support.

It means we can do more to bring this research, and it’s potential benefits, to communities that in the past were overlooked.

We have so many people to thank for all this. The scientists who do the work and championed our cause at the ballot box. The voters of California who once again showed their support for and faith in science. And the patients and patient advocates, the reason we were created and the reason we come to work every day.

As Dr. Maria Millan, our President & CEO, said in a letter to our team; “We are continually faced by great opportunities brilliantly disguised as insoluble problems.”  Here’s to the opportunities made possible by CIRM and for its continuation made possible by Prop 14!”

And none of this would be possible without the support of all of you. And for that we are truly Thankful.

From everyone at CIRM, we wish you a happy, peaceful and safe Thanksgiving.

CIRM-funded therapy to ease the impact of chemotherapy

Treatments for cancer have advanced a lot in recent years, but many still rely on the use of chemotherapy to either shrink tumors before surgery or help remove cancerous cells the surgery missed. The chemo can be very effective, but it’s also very toxic. Angiocrine Bioscience Inc. is developing a way to reduce those toxic side effects, and they just got a nice vote of confidence for that approach.

The US Food and Drug Administration (FDA) has granted Angiocrine Regenerative Medicine Advanced Therapy (RMAT) designation for their product AB-205.

RMAT is a big deal. It means the therapy, in this case AB-205, has already shown it is safe and potentially beneficial to patients, so the designation means that if it continues to be safe and effective it may be eligible for a faster, more streamlined approval process. And that means it can get to the patients who need it, outside of a clinical trial, faster.

What is AB-205? Well it’s made from genetically engineered cells, derived from cord blood, designed to help alleviate or accelerate recovery from the toxic side effects of chemotherapy for people undergoing treatment for lymphoma and other aggressive cancers of the blood or lymph system.

CIRM awarded Angiocrine Bioscience $6.2 million in 2018 to help carry out the Phase 2 clinical trial testing the therapy. In a news release ,CIRM President & CEO, Dr. Maria Millan, said there is a real need for this kind of therapy.

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

In a news release Dr. Paul Finnegan, Angiocrine’s CEO, welcomed the news.

“The RMAT designation speaks to the clinical meaningfulness and the promising efficacy data and safety profile of AB-205 based on our Phase 1b/2 study. This is an important step in accelerating the development of AB-205 towards its first market approval. We appreciate the thorough assessment provided by the FDA reviewers and the support from our partner, the California Institute for Regenerative Medicine.” 

The investment in Angiocrine marked a milestone for CIRM. It was the 50th clinical trial we had funded. It was a cause for celebration then. We’re hoping it will be a cause for an even bigger celebration in the not too distant future.

The company hopes to start a Phase 3 clinical trial in the US and Europe next year.

CIRM-Funded Clinical Trial for Sickle Cell Gives Hope to People Battling the Disease

Marissa Cors (right) with her mother Adrienne Shapiro

Marissa Cors has lived with Sickle Cell Disease (SCD) for more than 40 years. The co-founder of The Sickle Cell Experience Live, an online platform designed to bring more awareness to Sickle Cell Disease around the world, says it’s hard, knowing that at any moment you may have to put your life on hold to cope with another attack of excruciating pain.

“It is incredibly frustrating to have a disease that is constantly disrupting and interfering with your life. The daily pain and fatigue make it difficult to have a normal life. You may be experiencing manageable pain one minute and then a crisis will hit – knocking you to the ground with horrible pain and requiring pain management and hospitalization. It makes going to school or having a job or even a normal adult relationship near impossible.”

SCD is an inherited disease caused by a single gene mutation resulting in abnormal hemoglobin, which causes red blood cells to ‘sickle’ in shape.  Sickling of red blood cells clogs blood vessels and leads to progressive organ damage, pain crises, reduced quality of life, and early death. 

The disease affects around 100,000 Americans, mostly Black Americans but also members of the Latinx community. Marissa says coping with it is more than just a medical struggle. “Born into the cycle of fatigue, pain and fear. Depending on a healthcare system filled with institutionalized bias and racism. It is a life that is difficult on all facets.” 

CIRM is committed to trying find new treatments, and even a cure for SCD. That’s why the CIRM Board recently awarded $8,333,581 to Dr. David Williams at Boston Children’s Hospital to conduct a gene therapy clinical trial for sickle cell disease.  This is the second project that is part of an agreement between CIRM and the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, to co-fund cell and gene therapy programs under the NHLBI’s  “Cure Sickle Cell” Initiative.  The goal of this agreement is to markedly accelerate clinical development of cell and gene therapies to cure SCD.

In recent years we have made impressive strides in developing new approaches to treating sickle cell disease,” says Dr. Maria T. Millan, President & CEO of CIRM. “But we still have work to do. That’s why this partnership, this research is so important. It reflects our commitment to pushing ahead as fast as we can to find a treatment, a cure, that will help all the people battling the disease here in the U.S. and the estimated 20 million worldwide.”

The team will take a patient’s own blood stem cells and insert a novel engineered gene to silence abnormal hemoglobin and induce normal fetal hemoglobin expression.  The modified blood stem cells will then be reintroduced back into the patient.  The goal of this therapy is to aid in the production of normal shaped red blood cells, thereby reducing the severity of the disease. 

For Marissa, anything that helps make life easier will be welcome not just for people with SCD but their families and the whole community. “A stem cell cure will end generations of guilt, suffering, pain and early death. It will give SCD families relief from the financial, emotional and spiritual burden of caring someone living with SCD. It will give all of us an opportunity to have a normal life. Go to school, go to work, live with confidence.” 

CIRM Board Approves Four New Clinical Trials

A breakdown of CIRM’s clinical trials by disease area

This past Thursday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved four new clinical trials in addition to ten new discovery research awards.

These new awards bring the total number of CIRM-funded clinical trials to 68.  Additionally, these new additions have allowed the state agency to exceed the goal of commencing 50 new trials outlined in its five year strategic plan.

$8,970,732 was awarded to Dr. Steven Deeks at the University of California San Francisco (UCSF) to conduct a clinical trial that modifies a patient’s own immune cells in order to treat and potentially cure HIV. 

Current treatment of HIV involves the use of long-term antiretroviral therapy (ART).  However, many people are not able to access and adhere to long-term ART.

Dr. Deeks and his team will take a patient’s blood and extract T cells, a type of immune cell.  The T cells are then genetically modified to express two different chimeric antigen receptors (CAR), which enable the newly created duoCAR-T cells to recognize and destroy HIV infected cells.  The modified T cells are then reintroduced back into the patient.

The goal of this one time therapy is to act as a long-term control of HIV with patients no longer needing to take ART, in effect a form of HIV cure.  This approach would also address the needs of those who are not able to respond to current approaches, which is estimated to be 50% of those affected by HIV globally. 

$3,728,485 was awarded to Dr. Gayatri Rao from Rocket Pharmaceuticals to conduct a clinical trial using a gene therapy for infantile malignant osteopetrosis (IMO), a rare and life-threatening disorder that develops in infancy.  IMO is caused by defective bone cell function, which results in blindness, deafness, bone marrow failure, and death very early in life. 

The trial will use a gene therapy that targets IMO caused by mutations in the TCIRG1 gene.  The team will take a young child’s own blood stem cells and inserting a functional version of the TCIRG1 gene.  The newly corrected blood stem cells are then introduced back into the child, with the hope of halting or preventing the progression of IMO in young children before much damage can occur. 

Rocket Pharmaceuticals has used the same gene therapy approach for modifying blood stem cells in a separate CIRM funded trial for a rare pediatric disease, which has shown promising results.

$8,996,474 was awarded to Dr. Diana Farmer at UC Davis to conduct a clinical trial of in utero repair of myelomeningocele (MMC), the most severe form of spina bifida.  MMC is a birth defect that occurs due to incomplete closure of the developing spinal cord, resulting in neurological damage to the exposed cord.  This damage leads to lifelong lower body paralysis, and bladder and bowel dysfunction.

Dr. Farmer and her team will use placenta tissue to generate mesenchymal stem cells (MSCs).  The newly generated MSCs will be seeded onto an FDA approved dural graft and the product will be applied to the spinal cord while the infant is still developing in the womb.  The goal of this therapy is to help promote proper spinal cord formation and improve motor function, bladder function, and bowel function. 

The clinical trial builds upon the work of CIRM funded preclinical research.

$8,333,581 was awarded to Dr. David Williams at Boston Children’s Hospital to conduct a gene therapy clinical trial for sickle cell disease (SCD).  This is the second project that is part of an agreement between CIRM and the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, to co-fund cell and gene therapy programs under the NHLBI’s  “Cure Sickle Cell” Initiative.  The goal of this agreement is to markedly accelerate clinical development of cell and gene therapies to cure SCD.

SCD is an inherited disease caused by a single gene mutation resulting in abnormal hemoglobin, which causes red blood cells to ‘sickle’ in shape.  Sickling of red blood cells clogs blood vessels and leads to progressive organ damage, pain crises, reduced quality of life, and early death. 

The team will take a patient’s own blood stem cells and insert a novel engineered gene to silence abnormal hemoglobin and induce normal fetal hemoglobin expression.  The modified blood stem cells will then be reintroduced back into the patient.  The goal of this therapy is to aid in the production of normal shaped red blood cells, thereby reducing the severity of the disease.

“Today is a momentus occasion as CIRM reaches 51 new clinical trials, surpassing one of the goals outlined in its five year strategic plan,” says Maria T. Millan, M.D., President and CEO of CIRM.  “These four new trials, which implement innovative approaches in the field of regenerative medicine, reflect CIRM’s ever expanding and diverse clinical portfolio.”

The Board also approved ten awards that are part of CIRM’s Quest Awards Prgoram (DISC2), which promote promising new technologies that could be translated to enable broad use and improve patient care.

The awards are summarized in the table below:

  APPLICATION  TITLE  INSTITUTION  AWARD AMOUNT  
    DISC2-12169  Human-induced pluripotent stem cell-derived glial enriched progenitors to treat white matter stroke and vascular dementia.  UCLA  $250,000
  DISC2-12170Development of COVID-19 Antiviral Therapy Using Human iPSC-Derived Lung Organoids  UC San Diego  $250,000
  DISC2-12111Hematopoietic Stem Cell Gene Therapy for X-linked Agammaglobulinemia  UCLA  $250,000
  DISC2-12158Development of a SYF2 antisense oligonucleotide (ASO) treatment for ALSUniversity of Southern California  $249,997
    DISC2-12124Dual angiogenic and immunomodulating nanotechnology for subcutaneous stem cell derived islet transplantation for the treatment of diabetes  Lundquist Institute  $250,000
  DISC2-12105Human iPSC-derived chimeric antigen receptor-expressing macrophages for cancer treatment  UC San Diego  $250,000
  DISC2-12164Optimization of a human interneuron cell therapy for traumatic brain injury  UC Irvine  $250,000
  DISC2-12172Combating COVID-19 using human PSC-derived NK cells  City of Hope  $249,998
  DISC2-12126The First Orally Delivered Cell Therapy for the Treatment of Inflammatory Bowel Disease  Vitabolus Inc.  $249,000
    DISC2-12130Transplantation of Pluripotent Stem Cell Derived Microglia for the Treatment of Adult-onset Leukoencephalopathy (HDLS/ALSP)  UC Irvine  $249,968

Cures, clinical trials and unmet medical needs

When you have a great story to tell there’s no shame in repeating it as often as you can. After all, not everyone gets to hear first time around. Or second or third time. So that’s why we wanted to give you another opportunity to tune into some of the great presentations and discussions at our recent CIRM Alpha Stem Cell Clinic Network Symposium.

It was a day of fascinating science, heart-warming, and heart-breaking, stories. A day to celebrate the progress being made and to discuss the challenges that still lie ahead.

There is a wide selection of topics from “Driving Towards a Cure” – which looks at some pioneering work being done in research targeting type 1 diabetes and HIV/AIDS – to Cancer Clinical Trials, that looks at therapies for multiple myeloma, brain cancer and leukemia.

The COVID-19 pandemic also proved the background for two detailed discussions on our funding for projects targeting the coronavirus, and for how the lessons learned from the pandemic can help us be more responsive to the needs of underserved communities.

Here’s the agenda for the day and with each topic there’s a link to the video of the presentation and conversation.

Thursday October 8, 2020

View Recording: CIRM Fellows Trainees

9:00am Welcome Mehrdad Abedi, MD, UC Davis Health, ASCC Program Director  

Catriona Jamieson, MD,  View Recording: ASCC Network Value Proposition

9:10am Session I:  Cures for Rare Diseases Innovation in Action 

Moderator: Mark Walters, MD, UCSF, ASCC Program Director 

Don Kohn, MD, UCLA – View Recording: Severe combined immunodeficiency (SCID) 

Mark Walters, MD, UCSF, ASCC Program Director – View Recording: Thalassemia 

Pawash Priyank, View Recording: Patient Experience – SCID

Olivia and Stacy Stahl, View Recording: Patient Experience – Thalassemia

10 minute panel discussion/Q&A 

BREAK

9:55am Session II: Addressing Unmet Medical Needs: Driving Towards a Cure 

Moderator: John Zaia, MD, City of Hope, ASCC Program Direction 

Mehrdad Abedi, MD, UC Davis Health, ASCC Program Director – View Recording: HIV

Manasi Jaiman, MD, MPH, ViaCyte, Vice President, Clinical Development – View Recording: Diabetes

Jeff Taylor, Patient Experience – HIV

10 minute panel discussion/Q&A 

BREAK

10:40am Session III: Cancer Clinical Trials: Networking for Impact 

Moderator: Catriona Jamieson, MD, UC San Diego, ASCC Program Director 

Daniela Bota, MD, PhD, UC Irvine, ASCC Program Director – View Recording:  Glioblastoma 

Michael Choi, MD, UC San Diego – View Recording: Cirmtuzimab

Matthew Spear, MD, Poseida Therapeutics, Chief Medical Officer – View Recording: Multiple Myeloma  

John Lapham, Patient Experience –  View Recording: Chronic lymphocytic leukemia (CLL) 

10 minute panel discussion/Q&A 

BREAK

11:30am Session IV: Responding to COVID-19 and Engaging Communities

Two live “roundtable conversation” sessions, 1 hour each.

Roundtable 1: Moderator Maria Millan, MD, CIRM 

CIRM’s / ASCC Network’s response to COVID-19 Convalescent Plasma, Cell Therapy and Novel Vaccine Approaches

Panelists

Michael Matthay, MD, UC San Francisco: ARDS Program

Rachael Callcut, MD, MSPH, FACS, UC Davis: ARDS Program 

John Zaia, MD, City of Hope: Convalescent Plasma Program 

Daniela Bota, MD, PhD, UC Irvine: Natural Killer Cells as a Treatment Strategy 

Key questions for panelists: 

  • Describe your trial or clinical program?
  • What steps did you take to provide access to disproportionately impacted communities?
  • How is it part of the overall scientific response to COVID-19? 
  • How has the ASCC Network infrastructure accelerated this response? 

Brief Break

Roundtable 2: Moderator Ysabel Duron, The Latino Cancer Institute and Latinas Contra Cancer

View Recording: Roundtable 2

Community Engagement and Lessons Learned from the COVID Programs.  

Panelists

Marsha Treadwell, PhD, UC San Francisco: Community Engagement  

Sheila Young, MD, Charles R. Drew University of Medicine and Science: Convalescent Plasma Program in the community

David Lo, MD, PhD,  UC Riverside: Bringing a public health perspective to clinical interventions

Key questions for panelists: 

  • What were important lessons learned from the COVID programs? 
  • How can CIRM and the ASCC Network achieve equipoise among communities and engender trust in clinical research? 
  • How can CIRM and the ASCC Network address structural barriers (e.g. job constrains, geographic access) that limit opportunities to participate in clinical trials?

Exploring tough questions, looking for answers

COVID-19 and social and racial injustice are two of the biggest challenges facing the US right now. This Thursday, October 8th, we are holding a conversation that explores finding answers to both.

The CIRM Alpha Stem Cell Clinic Network Symposium is going to feature presentations about advances in stem cell and regenerative research, highlighting treatments that are already in the clinic and being offered to patients.

But we’re also going to dive a little deeper into the work we support, and use it to discuss two of the most pressing issues of the day.

One of the topics being featured is research into COVID-19. To date CIRM has funded 17 different projects, including three clinical trials. We’ll talk about how these are trying to find ways to help people infected with the virus, seeing if stem cells can help restore function to organs and tissues damaged by the virus, and if we can use stem cells to help develop safe and effective vaccines.

Immediately after that we are going to use COVID-19 as a way of exploring how the people most at risk of being infected and suffering serious consequences, are also the ones most likely to be left out of the research and have most trouble accessing treatments and vaccines.

Study after study highlights how racial and ethnic minorities are underrepresented in clinical trials and disproportionately affected by debilitating diseases. We have a responsibility to change that, to ensure that the underserved are given the same opportunity to take part in clinical trials as other communities.

How do we do that, how do we change a system that has resisted change for so long, how do we overcome the mistrust that has built up in underserved communities following decades of abuse? We’ll be talking about with experts who are on the front lines of this movement.

It promises to be a lively meeting. We’d love to see you there. It’s virtual – of course – it’s open to everyone, and it’s free.

Here’s where you can register and find out more about the Symposium