According to the Podcasthosting.org website there are some two million podcasts in the world. Make that two million and one. That’s because CIRM is launching its own podcast and doing it with one of the biggest names in biotech.
Our podcast is called – with a nod to The Who – “Talking ’bout (Re)Generation” and the first episode features our President & CEO Dr. Maria Millan interviewing Dr. Derrick Rossi, the co-founder of Moderna. Moderna, as I am sure you know, is the maker of one of the most effective vaccines against COVID.
In the interview Dr. Rossi talks about his early days as a postdoc at Stanford – supported by CIRM – and the career arc that led him to help create the company behind the vaccine, and what his plans are for the future. It’s a fun, chatty, lively interview; one you can listen to in the car, at home or wherever you listen to your podcasts.
We want the podcast to be fun for your ear holes and interesting and engaging for your brain. We’re going to be talking to scientists and researchers, doctors and nurses, patients and patient advocates and anyone else we think has something worth listening to.
We have other episodes planned and will share those with you in the near future. In the meantime, if you have any ideas or individuals you think would make a good subject for a podcast let us know, we are always happy to hear from you.
The University of California, San Francisco (UCSF), in collaboration with UC Berkeley (UCB) and UC Los Angeles (UCLA), have been given permission by the US Food and Drug Administration (FDA) to launch a first-in-human clinical trial using CRISPR technology as a gene-editing technique to cure Sickle Cell Disease.
This research has been funded by CIRM from the early stages and, in a co-funding partnership with theNational Heart, Lung, and Blood Institute under the Cure Sickle Cell initiatve, CIRM supported the work that allowed this program to gain FDA permission to proceed into clinical trials.
Sickle Cell Disease is a blood disorder that affects around 100,000 people, mostly Black and Latinx people in the US. It is caused by a single genetic mutation that results in the production of “sickle” shaped red blood cells. Normal red blood cells are round and smooth and flow easily through blood vessels. But the sickle-shaped ones are rigid and brittle and clump together, clogging vessels and causing painful crisis episodes, recurrent hospitalization, multi-organ damage and mini-strokes.
The three UC’s have combined their respective expertise to bring this program forward.
The CRISPR-Cas9 technology was developed by UC Berkeley’s Nobel laureate Jennifer Doudna, PhD. UCLA is a collaborating site, with expertise in genetic analysis and cell manufacturing and UCSF Benioff Children’s Hospital Oakland is the lead clinical center, leveraging its renowned expertise in cord blood and marrow transplantation and in gene therapy for sickle cell disease.
The approach involves retrieving blood stem cells from the patient and, using a technique involving electrical pulses, these cells are treated to correct the mutation using CRISPR technology. The corrected cells will then be transplanted back into the patient.
In a news release, UCSF’s Dr. Mark Walters, the principal investigator of the project, says using this new gene-editing approach could be a game-changer. “This therapy has the potential to transform sickle cell disease care by producing an accessible, curative treatment that is safer than the current therapy of stem cell transplant from a healthy bone marrow donor. If this is successfully applied in young patients, it has the potential to prevent irreversible complications of the disease. Based on our experience with bone marrow transplants, we predict that correcting 20% of the genes should be sufficient to out-compete the native sickle cells and have a strong clinical benefit.”
Dr. Maria T. Millan, President & CEO of CIRM, said this collaborative approach can be a model for tackling other diseases. “When we entered into our partnership with the NHLBI we hoped that combining our resources and expertise could accelerate the development of cell and gene therapies for SCD. And now to see these three UC institutions collaborating on bringing this therapy to patients is truly exciting and highlights how working together we can achieve far more than just operating individually.”
The 4-year study will include six adults and three adolescents with severe sickle cell disease. It is planned to begin this summer in Oakland and Los Angeles.
The three UCs combined to produce a video to accompany news about the trial. Here it is:
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.
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.
2020 has been, to say the very least, a difficult and challenging year for all of us. But while the focus of the world has, understandably, been on the coronavirus there was also some really promising advances in stem cell research. Those advances are captured in a great new documentary called Ending Disease.
The documentary is by Emmy award-winning filmmaker Joe Gantz. In it he follows ten people who are facing life-threatening or life-changing diseases and injuries and who turn to pioneering stem cell therapies for help.
It’s an inspiring documentary, one that reminds you of the real need for new treatments and the tremendous hope and promise of stem cell therapies. Here’s a look at a trailer for Ending Disease.
You can see an exclusive screening of Ending Disease on Friday, January 8th, 2021 at 5:00pm PST.
After the livestream, there will be a live Q&A session where former members of the successful Proposition 14 campaign team – which refunded CIRM with an additional $5.5 billion – will be joined by CIRM’s President and CEO Dr. Maria Millan, talking about what lies ahead for CIRM and the future of stem cell research.
To purchase a ticket, click here. It only costs $12 and 50% of the ticket sales proceeds will go to Americans for Cures to help them continue to advocate for the advancement of stem cell research, and more importantly, for the patients and families to whom stem cell research provides so much hope.
If you need any extra persuading that it’s something you should definitely put on our calendar, here’s a letter from the film maker Joe Gantz.
I am the director of the documentary Ending Disease: The Stem Cell, Anti-Cancer T-Cell, & Antibody Revolution In Medicine, a film that will help inform people about the progress that’s been made in this field and how people with their lives on the line are now able to benefit from these new regenerative therapies.
I was granted unprecedented access to ten of the first generation of clinical trials using stem cell and regenerative medicine to treat and cure many of the most devastating diseases and conditions including: brain cancer, breast cancer, leukemia and lymphoma, HIV, repairing a broken spinal cord, retinitis pigmentosa and SCID. The results are truly inspiring.
This is personal for me. After spending four years making this documentary, I was diagnosed with bladder cancer. Upon diagnosis, I immediately felt the same desperation as millions of families who are in search of a medical breakthrough. I understood, on a personal level, what the patients we followed in the film all knew: when you are diagnosed with a disease, there is a narrow window of time in which you can effectively seek a life-saving treatment or cure. If treatment becomes available outside of that window, then it is too late. However, Ending Disease shows that with continued support for regenerative medicine, we can create a near future in which one-time cures and highly mitigating therapies are available to patients for a whole host of diseases.
The US Food and Drug Administration (FDA) has granted Investigational New Drug (IND) permission enabling Graphite Bio to test the investigational, potentially revolutionary gene editing therapy GPH101 developed under the supervision of Matthew Porteus, MD, PhD, in a clinical trial for people with sickle cell disease (SCD).
The California Institute for Regenerative Medicine (CIRM) has been supporting this project with a $5.2 million grant, enabling Dr. Porteus and his team at the Institute of Stem Cell Biology and Regenerative Medicine at Stanford University to conduct the preclinical manufacturing and safety studies required by the FDA.
“We congratulate the Graphite Bio team for obtaining the IND, a critical step in bringing the GPH101 gene therapy forward for Sickle Cell Disease,” says Dr. Maria T. Millan, CIRM’s President & CEO. “CIRM is committed to the national Cure Sickle Cell initiative and are delighted that this technology, the product of CIRM funded research conducted by Dr. Porteus at Stanford, is progressing to the next stage of development”
Sickle cell disease is caused by a genetic mutation that turns normally smooth, round red blood cells into rigid, sickle shaped cells. Those cells clump together, clogging up blood vessels, causing intense pain, damaging organs and increasing the risk of strokes and premature death. There are treatments that help control the damage, but the only cure is a bone marrow stem cell transplant, which can only happen if the patient has a stem cell donor (usually a close relative) who has matching bone marrow.
The investigational therapy GPH101 harnesses the power of CRISPR and natural DNA repair mechanisms to cut out the single mutation in the sickle globin gene and paste in the correct “code.” Correction of this mutation would reverse the defect and result in healthy non-sickling red blood cells.
CEDAR, a Phase 1/2, multi-center, open-label clinical study is designed to evaluate the safety, preliminary efficacy and pharmacodynamics of GPH101 in adult and adolescent patients with severe SCD.
For patient advocate Nancy Rene, the news is personal: “It’s always exciting to hear about the progress being made in sickle cell research. If successful it will mean that my grandson, and especially other young adults, can look forward to a life free of pain and organ damage. They can actually begin to plan their lives, thinking about careers and families. I want to thank Dr. Porteus and all of the scientists who are working so hard for people with sickle cell disease. This is wonderful news.”
CIRM has funded four clinical trials for Sickle Cell Disease using different approaches and has a unique partnership with the National Heart, Lung and Blood Institutes under the NIH “Cure Sickle Cell” initiative.
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.
Funding models are rarely talked about in excited tones. It’s normally relegated to the dry tomes of academia. But in CIRM’s case, the funding model we have created is not just fundamental to our success in advancing regenerative medicine in California, it’s also proving to be a model that many other agencies are looking at to see if they can replicate it.
A recent article in the journal Cell & Gene Therapy Insights looks at what the CIRM model does and how it has achieved something rather extraordinary.
Full disclosure. I might be a tad biased here as the article was written by my boss, Dr. Maria Millan, and two of my colleagues, Dr. Sohel Talib and Dr. Shyam Patel.
I won’t go into huge detail here (you can get that by reading the article itself) But the article “highlights 3 elements of CIRM’s funding model that have enabled California academic researchers and companies to de-risk development of novel regenerative medicine therapies and attract biopharma industry support.”
Those three elements are:
1. Ensuring that funding mechanisms bridge the entire translational “Valley of Death”
2. Constantly optimizing funding models to meet the needs of a rapidly evolving industry
3. Championing the portfolio and proactively engaging potential industry partners
As an example of the first, they point to our Disease Team awards. These were four-year investments that gave researchers with promising projects the time, support and funds they needed to not only develop a therapy, but also move it out of academia into a company and into patients. Many of these projects had struggled to get outside investment until CIRM stepped forward. One example they offer is this one.
“CIRM Disease Team award funding also enabled Dr. Irving Weissman and the Stanford University team to discover, develop and obtain first-in-human clinical data for the innovative anti-CD47 antibody immunotherapy approach to cancer. The spin-out, Forty Seven, Inc., then leveraged CIRM funding as well as venture and public market financing to progress clinical development of the lead candidate until its acquisition by Gilead Sciences in April 2020 for $4.9B.”
But as the field evolved it became clear CIRM’s funding model had to evolve too, to better meet the needs of a rapidly advancing industry. So, in 2015 we changed the way we worked. For example, with clinical trial stage projects we reduced the average time from application to funding from 22 months to 120 days. In addition to that applications for new clinical stage projects were able to be submitted year-round instead of only once or twice a year as in the past.
We also created hard and fast milestones for all programs to reach. If they met their milestone funding continued. If they didn’t, funding stopped. And we required clinical trial stage projects, and those for earlier stage for-profit companies, to put up money of their own. We wanted to ensure they had “skin in the game” and were as committed to the success of their project as we were.
Finally, to champion the portfolio we created our Industry Alliance Program. It’s a kind of dating program for the researchers CIRM funds and companies looking to invest in promising projects. Industry partners get a chance to look at our portfolio and pick out projects they think are interesting. We then make the introductions and see if we can make a match.
And we have.
“To date, the IAP has also formally enrolled 8 partners with demonstrated commitment to cell and gene therapy development. The enrolled IAP partners represent companies both small and large, multi-national venture firms and innovative accelerators.
Over the past 18 months, the IAP program has enabled over 50 one-on-one partnership interactions across CIRM’s portfolio from discovery stage pluripotent stem cell therapies to clinical stage engineered HSC therapies.”
As the field continues to mature there are new problems emerging, such as the need to create greater manufacturing capacity to meet the growth in demand for high quality stem cell products. CIRM, like all other agencies, will also have to evolve and adapt to these new demands. But we feel with the model we have created, and the flexibility we have to pivot when needed, we are perfectly situated to do just that.
This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved two new discovery research project as part of the $5 million in emergency funding for COVID-19 related projects. This brings the number of COVID-19 projects CIRM is supporting to 17, including three clinical trials.
$249,974 was awarded to Dr. Karen Christman at UC San Diego to develop a treatment for Acute Respiratory Distress Syndrome (ARDS), a life-threatening lung injury that occurs when fluid leaks into the lungs and is prevalent in COVID-19 patients. Dr. Christman and her team will develop extracellular matrix (ECM) hydrogels, a kind of structure that provides support to surrounding cells. The goal is to develop a treatment that can be delivered directly to site of injury, where the ECM would recruit stem cells, treat lung inflammation, and promote lung healing.
$250,000 was awarded to Dr. Lili Yang at UCLA to develop a treatment for COVID-19. Dr. Yang and her team will use blood stem cells to create invariant natural killer T (iNKT) cells, a powerful kind of immune cell with the potential to clear virus infection and mitigate harmful inflammation. The goal is to develop these iNKT cells as an off the shelf therapy to treat patients with COVID-19.
These awards are part of CIRM’s Quest Awards Program (DISC2), which promotes promising new technologies that could be translated to enable broad use and improve patient care.
“The harmful lung inflammation caused by COVID-19 can be dangerous and life threatening,” says Maria T. Millan, M.D., the President and CEO of CIRM. “Early stage discovery projects like the ones approved today are vital in developing treatments for patients severely affected by the novel coronavirus.”
Earlier in the week the Board also approved changes to both DISC2 and clinical trial stage projects (CLIN2). These were in recognition of the Agency’s remaining budget and operational timeline and the need to launch the awards as quickly as possible.
For DISC2 awards the changes include:
Award limit of $250,000
Maximum award duration of 12 months
Initiate projects within 30 days of approval
All proposals must provide a statement describing how their overall study plan and design has considered the influence of race, ethnicity, sex and gender diversity.
All proposals should discuss the limitations, advantages, and/or challenges in developing a product or tools that addresses the unmet medical needs of California’s diverse population, including underserved communities.
Under the CLIN2 awards, to help projects carry out a clinical trial, the changes include:
Adjust award limit to the following:
Phase 1, Phase 1/2, Feasability Award Cap
Phase 2 Award Cap
Phase 3 Award Cap
Adjust the award duration to not exceed 3 years with award completion no later than November 2023
Initiate projects within 30 days of approval
All proposals must include a written plan in the application for outreach and study participation by underserved and disproportionately affected populations. Priority will be given to projects with the highest quality plans in this regard.
The changes outlined above for CLIN2 awards do not apply to sickle cell disease projects expected to be funded under the CIRM/NHLBI Cure Sickle Cell Disease joint Initiative.
This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved two additional discovery research projects as part of the $5 million in emergency funding for COVID-19 related projects. This brings the number of COVID-19 projects CIRM is supporting to 15, including three clinical trials.
The Board awarded $249,999 to Dr. Evan Snyder at the Sanford Burnham Prebys Medical Discovery Institute. The study will use induced pluripotent stem cells (iPSCs), a type of stem cell that can be created by reprogramming skin or blood cells, to create lung organoids. These lung organoids will then be infected with the novel coronavirus in order to test two drug candidates for treatment of the virus. The iPSCs and the subsequent lung organoids created will reflect diversity by including male and female patients from the Caucasian, African-American, and Latinx population.
This award is part of CIRM’s Quest Awards Program (DISC2), which promotes promising new technologies that could be translated to enable broad use and improve patient care.
The Board also awarded $150,000 to Dr. Steven Dowdy at UC San Diego for development of another potential treatment for COVID-19.
Dr. Dowdy and his team are working on developing a new, and hopefully more effective, way of delivering a genetic medicine, called siRNA, into the lungs of infected patients. In the past trying to do this proved problematic as the siRNA did not reach the appropriate compartment in the cell to become effective. However, the team will use an iPSC lung model to help them identify ways past this barrier so the siRNA can attack the virus and stop it replicating and spreading throughout the lungs.
This award is part of CIRM’s Inception Awards Program (DISC1), which supports transformational ideas that require the generation of additional data.
A supplemental award of $250,000 was approved for Dr. John Zaia at City of Hope to continue support of a CIRM funded clinical study that is using convalescent plasma to treat COVID-19 patients. The team recently launched a website to enroll patients, recruit plasma donors, and help physicians enroll their patients.
“The use of induced pluripotent stem cells has expanded the potential for personalized medicine,” says Dr. Maria T. Millan, the President & CEO of CIRM. “Using patient derived cells has enabled researchers to develop lung organoids and lung specific cells to test numerous COVID-19 therapies.”
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.”