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.
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 blog written by two of our fabulous Discovery and Translation team Science Officers, Dr. Kent Fitzgerald and Dr. Ross Okamura.
Dr. Ross Okamura
If you believe that you can know a person by their deeds, the partnership opportunities offered by CIRM illustrate what we, as an agency, believe is the most effective way to deliver on our mission statement, accelerating regenerative medicine treatments to patients with unmet medical needs.
Dr. Kent Fitzgerald
In our past, we have offered awards covering basic biology projects which in turn provided the foundation to produce promising therapies to ease human suffering. But those are only the first steps in an elaborate process.
In order to bring these potential therapies to the clinic, selected drug candidates must next go through a set of activities designed to prepare them for review by the Food and Drug Administration (FDA). For cell therapies, the first formal review is often the Pre- Investigational New Drug Application Consultation or pre-IND. This stage of drug development is commonly referred to as Translational, bridging the gap between our Discovery or early stage research and Clinical Trial programs.
One of our goals at CIRM is to prepare Translational projects we fund for that pre-IND meeting with the FDA, to help them gather data that support the hope this approach will be both safe and effective in patients. Holding this meeting with the FDA is the first step in the often lengthy process of conducting FDA regulated clinical trials and hopefully bringing an approved therapy to patients.
What type of work is required for a promising candidate to move from the Discovery stage into FDA regulated development? To address the needs of Translational science, CIRM offers the Translational Research Project funding opportunity. Activities that CIRM supports at the Translational stage include:
Process Development to allow manufacturing of the candidate therapy under Good Manufacturing Practices (GMP). This is to show that they can manufacture at a large enough scale to treat patients.
Assay development and qualification of measurements to determine whether the drug is being manufactured safely while retaining its curative properties.
Studies to determine the optimal dose and the best way to deliver that dose.
Pilot safety studies looking how the patient might respond after treatment with the drug.
The development of a clinical plan indicating under what rules and conditions the drug might be prescribed to a patient.
These, and other activities supported under our Translational funding program, all help to inform the FDA when they consider what pivotal studies they will require prior to approving an Investigational New Drug (IND) application, the next step in the regulatory approval process.
Since CIRM first offered programs specifically aimed at addressing the Translational stage of therapeutic candidates we have made 41 awards totaling approximately $150 million in funding. To date, 13 have successfully completed and achieved their program goals, while 19 others are still actively working towards meeting their objective. Additionally, three (treating Spina Bifida, Osteonecrosis, and Sickle Cell Disease) of the 13 programs have gone on to receive further CIRM support through our Clinical Stage programs.
During our time administering these awards, CIRM has actively partnered with our grantees to navigate what is required to bring a therapy from the bench to the bedside. CIRM operationalizes this by setting milestones that provide clear definitions of success, specific goals the researchers have to meet to advance the project and also by providing resources for a dedicated project manager to help ensure the project can keep the big picture in mind while executing on their scientific progress.
Throughout all this we partner with the researchers to support them in every possible way. For example, CIRM provides the project teams with Translational Advisory Panels (TAPs, modeled after the CIRM’s Clinical Advisory Panels) which bring in outside subject matter experts as well as patient advocates to help provide additional scientific, regulatory and clinical expertise to guide the development of the program at no additional cost to the grantees. One of the enduring benefits that we hope to provide to researchers and organizations is a practical mastery of translational drug development so that they may continue to advance new and exciting therapies to all patients.
Through CIRM’s strong and continued support of this difficult stage of development, CIRM has developed an internal practical expertise in advancing projects through Translation. We employ our experience to guide our awardees so they can avoid common pitfalls in the development of cell and gene therapies. The end goal is simple, helping to accelerate their path to the clinic and fulfilling the mission of CIRM that has been twice given to us by the voters of California, bringing treatments to patients suffering from unmet medical needs.
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…..”
Last November Marissa Cors, a patient advocate in the fight against Sickle Cell Disease (SCD), told the Stem Cellar “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.” With each passing month it seems we are getting closer to that day.
CIRM is funding four clinical trials targeting SCD and another project we are supporting has just been given the green light by the Food and Drug Administration to start a clinical trial. Clearly progress is being made.
Yesterday we got a chance to see that progress. We held a Zoom event featuring Marissa Cors and other key figures in the fight against SCD, CIRM Science Officer Dr. Ingrid Caras and Evie Junior. Evie is a pioneer in this struggle, having lived with sickle cell all his life but now hoping to live his life free of the disease. He is five months past a treatment that holds out the hope of eradicating the distorted blood cells that cause such devastation to people with the disease.
You can listen to his story, and hear about the other progress being made. Here’s a recording of the Zoom event.
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 have a guest blog by CIRM Senior Science Officer Lisa Kadyk, outlining how she and her colleagues actively search for the best science to fund.
Lisa Kadyk, Ph.D.
Hi everyone,
This is Lisa Kadyk, a Science Officer from the CIRM Therapeutics team, here to tell you about some of the work our team does to support the CIRM mission of accelerating stem cell treatments to patients with unmet medical needs. Our job involves seeking out and recruiting great scientists to apply to CIRM and supporting those we fund.
Therapeutics team members manage both the awards that fund the final preclinical studies required before testing a therapeutic in a clinical trial (CLIN1), and the awards that fund the clinical trials themselves (CLIN2).
I mentioned above that we actively recruit new applicants for our CLIN1 and CLIN2 awards – which is not an activity that is typical of most funding agencies – so why and how do we do this?
It all comes down to our mission of accelerating the development of therapies to help patients with unmet medical needs. It turns out that there are many potential applicants developing cutting edge therapies who don’t know much or anything about CIRM, and the ways we can help them with getting those therapies to the clinic and through clinical trials. So, to bridge this gap, we Science Officers attend scientific conferences, read the scientific literature and meet regularly with each other to stay abreast of new therapeutic approaches being developed in both academia and industry, with the goal of identifying and reaching out to potential applicants about what CIRM has to offer.
What are some of the things we tell potential applicants about how partnering with CIRM can help accelerate their programs? First of all, due to the efforts of a very efficient Review team, CIRM is probably the fastest in the business for the time between application and potential funding. It can be as short as three months for a CLIN1 or CLIN2 application to be reviewed by the external Grants Working Group and approved by the CIRM Board, whereas the NIH (for example) estimates it takes seven to ten months to fund an application. Second, we have frequent application deadlines (monthly for CLIN1 and CLIN2), so we are always available when the applicant is ready to apply. Third, we have other accelerating mechanisms in place to help grantees once they’ve received funding, such as the CIRM Alpha Stem Cell Clinics network of six clinical sites throughout California (more efficient clinical trial processes and patient recruitment) and Clinical Advisory Panels (CAPs) – that provide technical, clinical or regulatory expertise as well as patient advocate guidance to the grantee. Finally, we Science Officers do our best to help every step of the way, from application through grant closeout.
We now feel confident that our recruitment efforts, combined with CIRM’s more efficient funding pipeline and review processes, are accelerating development of new therapies. Back in 2016, a new CIRM Strategic Plan included the goal of recruiting 50 successful (i.e., funded) clinical trial applicants within five years. This goal seemed like quite a stretch, since CIRM had funded fewer than 20 clinical trials in the previous ten years. Fast-forward to the end of 2020, and CIRM had funded 51 new trials in those five years, for a grand total of 68 trials.
Now, with the passage of Proposition 14 this past November, we are looking forward to bringing more cell and gene therapeutic candidates into clinical trials. If you are developing one yourself, feel free to let us know… or don’t be surprised if you hear from us!
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 look at a way of making blood stem cell transplants safer and more readily available
Unfortunately, there is still a certain degree of risk that accompanies this procedure. Before a blood stem cell transplant can be performed, diseased or defective blood stem cells in the patient’s bone marrow need to be removed using chemotherapy or radiation to make room for the transplant. This leaves the patient temporarily without an immune system and at risk for a life-threatening viral infection. Additionally, viral infections pose a serious risk to patients with immune deficiency disorders, with viruses accounting upwards of 40% of deaths in these patients.
That’s why in October 2017, the CIRM ICOC Board awarded $4.8M to fund a clinical trial conducted by Dr. Michael Pulsipher at the Children’s Hospital of Los Angeles. Dr. Pulsipher and his team are using virus-specific T cells (VSTs), a special type of cell that plays an important role in the immune response, to treat immunosuppressed or immune deficient patients battling life-threatening viral infections. This trial includes patients with persistent viral infections after having received a blood stem cell transplant as well as those with immune deficiency disorders that have not yet received a blood stem cell transplant. The VSTs used in this trial specifically treat cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus infections. They are manufactured using cells from healthy donors and are banked so as to be readily available when needed.
One challenge of receiving a stem cell transplant can be finding a patient and donor that are a close or identical match. This is done by looking at specific human leukocyte antigens (HLA), which are protein molecules we inherit from our parents. To give you an idea of how challenging this can be, you only have a 25% chance of being an HLA identical match with your sibling.
Because VSTs are temporary soldiers that are administered to fight the viral infection and then disappear, Dr. Pulsipher and his team are using partially HLA-matched VSTs to treat patients in their trial. Previous studies have indicated that partially HLA-matched T-cells can be effective in treating patients. The availability of partially HLA-matched VST banks that can be used “off the shelf” improves accessibility and shortens the time for patients to receive VST therapy, which will save lives.
To learn more about Dr. Pulsipher’s work, please view the video below:
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 take a deeper dive into CIRM’s Alpha Stem Cell Clinics Network. The following is written by Dr. Geoff Lomax, Senior Officer of CIRM Therapeutics and Strategic Infrastructure.
The year 2014 has been described as the regenerative medicine renaissance: the European Union approved its first stem cell-based therapy and the FDA authorized ViaCyte’s CIRM funded clinical trial for diabetes. A path forward for stem cell treatments had emerged and there was a growing pipeline of products moving towards the clinic. At the time, many in the field came to recognize the need for clinical trial sites with the expertise to manage this growing pipeline. Anticipating this demand, CIRM’s provided funding for a network of medical centers capable of supporting all aspect of regenerative medicine clinical trials. In 2015, the Alpha Stem Cell Clinics Network was launched to for this purpose.
The Alpha Clinics Network is comprised of leading California medical centers with specific expertise in delivering patient-centered stem cell and gene therapy treatments. UC San Diego, City of Hope, UC Irvine and UC Los Angeles were included in the initial launch, and UC San Francisco and UC Davis entered the network in 2017. Between 2015 and 2020 these sites supported 105 regenerative medicine clinical trials. Twenty-three were CIRM-funded clinical trials and the remaining 82 were sponsored by commercial companies or the Alpha Clinic site. These trials are addressing unmet medical needs for almost every disease where regenerative medicine is showing promise including blindness, blood disorders (e.g. sickle cell disease) cancer, diabetes, HIV/AIDS, neurological diseases among others.
As of spring of 2020 the network had inked over $57 million in contracts with commercial sponsors. High demand for Alpha Clinics reflects the valuable human and technical resources they provide clinical trial sponsors. These resources include:
Skilled patient navigators to educate patients and their families about stem cell and gene therapy treatments and assist them through the clinical trial process.
Teams and facilities specialized in the manufacturing and/or processing of patients’ treatments. In some instances, multiple Alpha Clinic sites collaborate in manufacturing and delivery of a personalized treatment to the patient.
Nurses and clinicians with experience with regenerative medicine and research protocols to effectively deliver treatments and subsequently monitor the patients.
The multi- site collaborations are an example of how the network operates synergistically to accelerate the development of new treatments and clinical trials. For example, the UC San Francisco Alpha Clinic is collaborating with UC Berkeley and the UC Los Angeles Alpha Clinic to develop a CIRM-funded gene therapy for sickle cell disease. Each partner brings a unique expertise to the program that aims to correct a genetic mutilation in the patients’ blood stem cells to effectively cure the disease. Most recently, City of Hope has partnered with UC Irvine and UC San Diego as part of CIRM’s COVID-19 research program to study how certain immune system antibodies might be used as a treatment for respiratory disease in infected patients. In another COVID-19 study, UC Irvine and UC Davis are working with a commercial sponsor to evaluate a treatment for infected adults.
The examples above are a small sample of the variety of collaborations CIRM funding has enabled. As the Alpha Clinics track record grown, sponsors are increasingly coming to California to enable the success of their research programs. Sponsors with trials running across the country have noted a desire to expand their number of Alpha Clinic sties because they consistently perform at the highest level.
Back in 2014, it was hard to imagine over one hundred clinical trials would be served by the CIRM network in just five years. Fortunately, CIRM was able to draw on the knowledge of its internal team, external advisors and the ICOC to anticipate this need and provide California infrastructure to rise to the occasion.
All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the people of California 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.
Dr. John Zaia, City of Hope stem cell researcher
The news that effective vaccines have been developed to help fight COVID-19 was a truly bright spot at the end of a very dark year. But it will be months, in some countries years, before we have enough vaccines to protect everyone. That’s why it’s so important to keep pushing for more effective ways to help people who get infected with the virus.
One of those ways is in a clinical study that CIRM is funding with City of Hope’s Dr. John Zaia. Dr. Zaia and his team, in partnership with the Translational Genomics Research Institute (TGen) in Flagstaff, Arizona, are using something called convalescent plasma to try and help people who have contracted the virus. Here’s the website they have created for the study.
Plasma is a part of our blood that carries proteins, called antibodies, that help defend our bodies against viral infections. When a patient recovers from COVID-19, their blood plasma contains antibodies against the virus. The hope is that those antibodies can now be used as a potential treatment for COVID-19 to help people who are newly infected.
For the study to succeed they’ll first need people who have recovered from the virus to donate blood. That’s particularly appropriate in January because this is National Volunteer Blood Donor Month.
The team has three elements to their approach:
A rapid-response screening program to screen potential COVID-19 convalescent plasma donors, particularly in underserved communities.
A laboratory center that can analyze the anti-SARS-CoV-2 antibodies properties in COVID-19 convalescent plasma.
An analysis of the clinical course of the disease in COVID-19 patients to identify whether antibody properties correlate with clinical benefit of COVID-19 convalescent plasma.
There’s reason to believe this approach might work. A study published this week in the New England Journal of Medicine, found that blood plasma from people who have recovered from COVID-19 can help older adults and prevent them from getting seriously ill with the virus if they get the plasma within a few days of becoming infected.
We are used to thinking of blood donations as being used to help people after surgery or who have been in an accident. In this study the donations serve another purpose, but one that is no less important. The World Health Organization describes blood as “the most precious gift that anyone can give to another person — the gift of life. A decision to donate your blood can save a life, or even several if your blood is separated into its components — red cells, platelets and plasma.”
That plasma could help in developing more effective treatments against the virus. Because until we have enough vaccines for everyone, we are still going to need as much help as we can get in fighting COVID-19. The recent surge in cases throughout the US and Europe are a reminder that this virus is far from under control. We have already lost far too many people. So, if you have recently recovered from the virus, or know someone who has, consider donating blood to this study. It could prove to be a lifesaver.
For more information about the study and how you can be part of it, click here.
Dr. Gil Sambrano, Vice President Portfolio & Review
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 take a look at our Review team.
Many people who have to drive every day don’t really think about what’s going on under the hood of their car. As long as the engine works and gets them from A to B, they’re happy. I think the same is true about CIRM’s Review team. Many people don’t really think about all the moving parts that go into reviewing a promising new stem cell therapy.
But that’s a shame, because they are really missing out on watching a truly impressive engine at work.
Just consider the simple fact that since CIRM started about 4,000 companies, groups and individuals have applied to us for funding. Just take a moment to consider that number. Four thousand. Then consider that at no time have there been more than 5 people working in the review team. That’s right. Just 5 people. And more recently there have been substantially fewer. That’s a lot of projects and not a lot of people to review them. So how do they do it? Easy. They’re brilliant.
First, as applications come in they are scrutinized to make sure they meet specific eligibility requirements; do they involve stem cells, is the application complete, is it the right stage of research, is the budget they are proposing appropriate for the work they want to do etc. If they pass that initial appraisal, they then move on to the second round, the Grants Working Group or GWG.
The GWG consists of independent scientific experts from all over the US, all over the world in fact. However, none are from California because we want to ensure there are no possible conflicts of interest. When I say experts, I do mean experts. These are among the top in their field and are highly sought after to do reviews with the National Institutes of Health etc.
Mark Noble, PhD, the Director of the Stem Cell and Regenerative Medicine Institute at the University of Rochester, is a long-time member of the GWG. He says it’s a unique group of people:
“It’s a wonderful scientific education because you come to these meetings and someone is putting in a grant on diabetes and someone’s putting in a grant on repairing the damage to the heart or spinal cord injury or they have a device that will allow you to transplant cells better and there are people in the room that are able to talk knowledgeably about each of these areas and understand how this plays into medicine and how it might work in terms of actual financial development and how it might work in the corporate sphere and how it fits in to unmet medical needs . I don’t know of any comparable review panels like this that have such a broad remit and bring together such a breadth of expertise which means that every review panel you come to you are getting a scientific education on all these different areas, which is great.”
The GWG reviews the projects for scientific merit: does the proposal seem plausible, does the team proposing it have the experience and expertise to do the work etc. The reviewers put in a lot of work ahead of time, not just reviewing the application, but looking at previous studies to see if the new application has evidence to support what this team hope to do, to compare it to other efforts in the same field. There are disagreements, but also a huge amount of respect for each other.
Once the GWG makes its recommendations on which projects to fund and which ones not to, the applications move to the CIRM Board, which has the final say on all funding decisions. The Board is given detailed summaries of each project, along with the recommendations of the GWG and our own CIRM Review team. But the Board is not told the identity of any of the applicants, those are kept secret to avoid even the appearance of any conflict of interest.
The Board is not required to follow the recommendations of the GWG, though they usually do. But the Board is also able to fund projects that the GWG didn’t place in the top tier of applications. They have done this on several occasions, often when the application targeted a disease or disorder that wasn’t currently part of the agency’s portfolio.
So that’s how Review works. The team, led by Dr. Gil Sambrano, does extraordinary work with little fanfare or fuss. But without them CIRM would be a far less effective agency.
The passage of Proposition 14 means we now have a chance to resume full funding of research, which means our Review team is going to be busier than ever. They have already started making changes to the application requirements. To help let researchers know what those changes are we are holding a Zoom webinar tomorrow, Thursday, at noon PST. If you would like to watch you can find it on our YouTube channel. And if you have questions you would like to ask send them to info@cirm.ca.gov
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.We kick off this event with a letter from our the Chair of our Board, Jonathan Thomas.
When voters approved Proposition 14 last November, they gave the Stem Cell Agency a new lease on life and a chance to finish the work we began with the approval of Proposition 71 in 2004. It’s a great honor and privilege. It’s also a great responsibility. But I think looking back at what we have achieved over the last 16 years shows we are well positioned to seize the moment and take CIRM and regenerative medicine to the next level and beyond.
When we started, we were told that if we managed to get one project into a clinical trial by the time our money ran out we would have done a good job. As of this moment we have 68 clinical trials that we have funded plus another 31 projects in clinical trials where we helped fund crucial early stage research. That inexorable march to therapies and cures will resume when we take up our first round of Clinical applications under Prop 14 in March.
But while clinical stage projects are the end game, where we see if therapies really work and are safe in people, there’s so much more that we have achieved since we were created. We have invested $900 million in basic research, creating a pipeline of the most promising stem cell research programs, as well as investing heavily on so-called “translational” projects, which move projects from basic science to where they’re ready to apply to the Food and Drug Administration (FDA) to begin clinical trials.
We have funded more than 1,000 projects, with each one giving us valuable information to help advance the science. Our funding has helped attract some of the best stem cell scientists in the world to California and, because we only fund research in California, it has persuaded many companies to either move here or open offices here to be eligible for our support. We have helped create the Alpha Stem Cell Clinics, a network of leading medical centers around the state that have the experience and expertise to deliver stem cell therapies to patients. All of those have made California a global center in the field.
That result is producing big benefits for the state. An independent Economic Impact Analysis reported that by the end of 2018 we had already helped generate an extra $10.7 billion in new sales revenue and taxes for California, hundreds of millions more in federal taxes and created more than 56,000 new jobs.
Used our support for stem cell research to leverage an additional $12 billion in private funding for the field.
Enrolled more than 2700 patients in CIRM funded clinical trials
In many ways our work is just beginning. We have laid the groundwork, helped enable an extraordinary community of researchers and dramatically accelerated the field. Now we want to get those therapies (and many more) over the finish line and get them approved by the FDA so they can become available to many more people around the state, the country and the world.
We also know that we have to make these therapies available to all people, regardless of their background and ability to pay. We have to ensure that underserved communities, who were often left out of research in the past, are an integral part of this work and are included in every aspect of that research, particularly clinical trials. That’s why we now require anyone applying to us for funding to commit to engaging with underserved communities and to have a written plan to show how they are going to do that.
Over the coming month, you will hear more about some of the remarkable things we have managed to achieve so far and get a better sense of what we hope to do in the future. We know there will be challenges ahead and that not everything we do or support will work. But we also know that with the team we have built at CIRM, the brilliant research community in California and the passion and drive of the patient advocate community we will live up to the responsibility the people of California placed in us when they approved Proposition 14.
The Stem Cellar 