A word from our Chair, several in fact

In 2005, the New Oxford American Dictionary named “podcast” its word of the year. At the time a podcast was something many had heard of but not that many actually tuned in to. My how times have changed. Now there are some two million podcasts to chose from, at least according to the New York Times, and who am I to question them.

Yesterday, in the same New York Times, TV writer Margaret Lyons, wrote about how the pandemic helped turn her from TV to podcasts: “Much in the way I grew to prefer an old-fashioned phone call to a video chat, podcasts, not television, became my go-to medium in quarantine. With their shorter lead times and intimate production values, they felt more immediate and more relevant than ever before.”

I mention this because an old colleague of ours at CIRM, Neil Littman, has just launched his own podcast and the first guest on it was Jonathan Thomas, Chair of the CIRM Board. Their conversation ranged from CIRM’s past to the future of the regenerative field as a whole, with a few interesting diversions along the way. It’s fun listening. And as Margaret Lyons said it might be more immediate and more relevant than ever before.

You can’t take it if you don’t make it

Biomedical specialist Mamadou Dialio at work in the Cedars-Sinai Biomanufacturing Center. Photo by Cedars-Sinai.

Following the race to develop a vaccine for COVID-19 has been a crash course in learning how complicated creating a new therapy is. It’s not just the science involved, but the logistics. Coming up with a vaccine that is both safe and effective is difficult enough, but then how do you make enough doses of it to treat hundreds of millions of people around the world?

That’s a familiar problem for stem cell researchers. As they develop their products they are often able to make enough cells in their own labs. But as they move into clinical trials where they are testing those cells in more and more people, they need to find a new way to make more cells. And, of course, they need to plan ahead, hoping the therapy is approved by the Food and Drug Administration, so they will need to be able to manufacture enough doses to meet the increased demand.

We saw proof of that planning ahead this week with the news that Cedars-Sinai Medical Center in Los Angeles has opened up a new Biomanufacturing Center.

Dr. Clive Svendsen, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, said in a news release, the Center will manufacture the next generation of drugs and regenerative medicine therapies.

“The Cedars-Sinai Biomanufacturing Center leverages our world-class stem-cell expertise, which already serves scores of clients, to provide a much-needed biomanufacturing facility in Southern California. It is revolutionary by virtue of elevating regenerative medicine and its therapeutic possibilities to an entirely new level-repairing the human body.”

This is no ordinary manufacturing plant. The Center features nine “clean rooms” that are kept free from dust and other contaminants. Everyone working there has to wear protective suits and masks to ensure they don’t bring anything into the clean rooms.

The Center will specialize in manufacturing induced pluripotent stem cells, or iPSCs. Dhruv Sareen, PhD, executive director of the Biolmanufacturing Center, says iPSCs are cells that can be turned into any other kind of cell in the body.

“IPSCs are powerful tools for understanding human disease and developing therapies. These cells enable us to truly practice precision medicine by developing drug treatments tailored to the individual patient or groups of patients with similar genetic profiles.”

The Biomanufacturing Center is designed to address a critical bottleneck in bringing cell- and gene-based therapies to the clinic. After all, developing a therapy is great, but it’s only half the job. Making enough of it to help the people who need it is the other half.

CIRM is funding Dr. Svendsen’s work in developing therapies for ALS and other diseases and disorders.  

Thank you

Bob Klein

These last few days have been interesting on so many levels. First the presidential race has kept the nation on tenterhooks. Closer to home the vote count for Proposition 14, to refunded CIRM, has been painstakingly slow (by the way, painstakingly means “with great care and thoroughness” for which we thank all the vote counters). But now, finally, happily, we have a verdict.

WE WON.

 It was close, desperately so. In the end the Associated Press called the race with the count at 51% yes, to 49% no. You can understand why so many of us were so nervous for so long. But now we have something to celebrate.

As Jonathan Thomas, JD, PhD, the Chair of our Board said: “We are thrilled to see Proposition 14 approved by the voters of California. We are proud of what we have achieved so far – the cures and therapies we helped develop, the billions we brought into the state in additional investments, and the tens of thousands of jobs we created – and we look forward to continuing that work.

“We are honored by the trust the people of California have placed in us, and by the support of our extraordinary patient advocate community and by the many Chambers of Commerce around California who have all recognized our historic achievements.

“We are already working on ways to repay that trust and bring stem cell and regenerative therapies to all the people of this great state, particularly for communities that have traditionally been overlooked or underserved.” 

In a news release on the Californians for Cures website, Bob and Danielle Klein, who led the Yes on 14 campaign, were understandably delighted:  

“The success of Prop. 14 sends a clear message from California voters that one of the most important investments our state can make is in the future health of our families. Over the past decade, California has made incredibly thoughtful and impactful investments in developing stem cell therapies and cures for diseases and conditions like diabetes, cancer, blindness, Parkinson’s, paralysis and many more; now we know this progress and work to mitigate human suffering, restore health and improve the human condition will continue. A special thank you to California’s voters and our supporters in passing this critical measure. Today would not have been possible without our historically unprecedented coalition of patient advocate organizations and individuals – the heart and soul of this campaign – who worked tirelessly to overcome all obstacles and help secure a victory for patients and their families, and deliver hope to those searching for a cure for generations to come.”

To all of you who voted for us, thank you from the bottom of our hearts.

To all the people who worked so hard to get Prop 14 passed, thank you. We are indebted to you.

OK, gotta go. We have work to do.

Stem cell therapy for deadly childhood immune disorder goes four for four

The gold standard for any new therapy in the U.S. is approval by the Food and Drug Administration (FDA). This approval clears the therapy for sale and often also means it will be covered by insurance. But along the way there are other designations that can mean a lot to a company developing a new approach to a deadly disease.

That’s what recently happened with Mustang Bio’s MB-107. The therapy was given Orphan Drug Designation for the treatment of X-linked Severe Combined Immunodeficiency (SCID) also known as “bubble baby disease”, a rare but deadly immune disorder affecting children. This is the same therapy that CIRM is funding in a clinical trial we’ve blogged about in the past.  

Getting Orphan Drug Designation can be a big deal. It is given to therapies intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S. It comes with some sweet incentives, such as tax credits toward the cost of clinical trials and prescription drug user fee waivers. And, if the product becomes the first in its class to get FDA approval for a particular disease, it is entitled to seven years of market exclusivity, which is independent from intellectual property protection.

This is not the first time Mustang Bio’s MB-107 has been acknowledged as a potential gamechanger. It’s also been given three other classifications both here in the US and in Europe.

  • Rare Pediatric Disease Designation: this also applies to treatments for diseases affecting fewer than 200,000 people in the US that have the potential to provide clinically meaningful benefits to patients. It provides the company with a “voucher” that they can use to apply for priority review for another therapy they are developing. The hope is that this will encourage companies to develop treatments for rare childhood diseases that might not otherwise be profitable.
  • Regenerative Medicine Advanced Therapy (RMAT) designation: this allows for faster, more streamlined approvals of regenerative medicine products
  • Advanced Therapy Medicinal Product classification: this is granted by the European Medicines Agency (EMA) to medicines that are based on genes, tissues or cells and can offer groundbreaking opportunities for the treatment of disease.

Of course, none of these designations are a guarantee that Mustang Bio’s MB-107 will ultimately get FDA approval, but they’re a pretty good indication that a lot of people have confidence they’ll get there.

A model for success

Dr. Maria Millan, CIRM’s President & CEO

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.

Battling COVID and turning back the clock on stem cell funding

Coronavirus

Battling the virus that causes COVID-19 is something that is top of everyone’s mind right now. That’s why CIRM is funding 17 different projects targeting the virus. But one of the most valuable tools in helping develop vaccines against a wide variety of diseases in the past is now coming under threat. We’ll talk about both issues in a live broadcast we’re holding on Wednesday, October 14th at noon (PDT).

That date is significant because it’s Stem Cell Awareness Day and we thought it appropriate to host a meeting looking at two of the most important issues facing the field.

The first part of the event will focus on the 17 projects that CIRM is funding that target COVID-19. This includes three clinical trials aiming to treat people who have been infected with the virus and are experiencing some of the more severe effects, such as damaged lungs.

We’ll also look at some of the earlier stage research that includes:

  • Work to help develop a vaccine
  • Using muscle stem cells to help repair damage to the diaphragm in patients who have spent an extended period on a ventilator
  • Boosting immune system cells to help fight the virus

The second part of the event will look at ways that funding for stem cell research at the federal level is once again coming into question. The federal government has already imposed new restrictions on funding for fetal tissue research, and now there are efforts in Congress to restrict funding for embryonic stem cell research.

The impacts could be significant. Fetal tissue has been used for decades to help develop some of the most important vaccines used today including rubella, chickenpox, hepatitis A, and shingles. They have also been used to make approved drugs against diseases including hemophilia, rheumatoid arthritis, and cystic fibrosis.

We’ll look at some of the reasons why we are seeing these potential restrictions on the medical research and what impact they could have on the ability to develop new treatments for the coronavirus and other deadly diseases.

You can watch the CIRM Stem Cell Awareness Day live event by going here: https://www.youtube.com/c/CIRMTV/videos at noon on Wednesday, October 14th.

Feel free to share news about this event with anyone you think might be interested.

We look forward to seeing you there.

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.

Enabling the Best Choice for Patients: The Need for Effective Patient Navigation

Making sure patients get the treatment they need and not a “snake oil” substitute

We are at a turning point in regenerative medicine as the first wave of treatments have obtained FDA approval. But at the same time as we see the advance of scientifically rigorous research and regulated products we are also witnessing the continued proliferation of “unproven treatments.” This dueling environment can be overwhelming and distracting to individuals and families trying to manage life-threatening diseases.

How does a patient navigate this environment and get trusted and reliable information to help sort through their options?

CIRM teamed up with the CURA Foundation to organize a roundtable discussion intended to answer this question. The conversation included thought leaders involved in patient advocacy, therapy research and development, public policy and research funding. The roundtable was divided into three segments designed to discuss:

  1. Examples of state-of-the-art patient navigation systems,
  2. Policy, research and infrastructure needs required to expand navigation systems, and
  3. Communication needs for engaging patients and the broader community.

Examples of Navigation Systems:

This session was framed around the observation that patients often do not get the best medicines or treatments available for their condition. For example, in the area of cancer care there is evidence that the top 25% of cancers are not being treated optimally. Historic barriers to optimal treatment include cost pressures that may block access to treatments, lack of knowledge about the available treatments or the absence of experts in the location where the patient is being treated.  Much of the session focused on how these barriers are being overcome by partnerships between health care provides, employers and patients.

For example, new technologies such as DNA sequencing and other cell-based markers enable better diagnosis of a patient’s underlying disease. This information can be collected by a community hospital and shared with experts who work with the treating doctor to consider the best options for the patient. If patients need to access a specialty center for treatment, there are new models for the delivery of such care. Emphasis is placed on building a relationship with the patient and their family by surrounding them with a team that can address any questions that arise. The model of patient-centered care is being embraced by employers who are purchasing suites of services for their employees.

Patient advocacy groups have also supported efforts to get the best information about the patients’ underlying disease. Advocacy organizations have been building tools to connect patients with researchers with the aim of allowing secure and responsible sharing of medical information to drive the patient-centered development of new treatments. In a related initiative, the American Society of Hematology is creating a data hub for clinical trials for sickle cell disease. Collectively, these efforts are designed to accelerate new treatments by allowing critical data to be shared among researchers.

Essential Policy Infrastructure for Regenerative Medicine:

Session two dovetailed nicely with first discussion. There was continued emphasis on the need for additional evidence (data) to demonstrate that regenerative medicine treatments are having a significant effect on the patient’s disease. Various speakers echoed the need for patients in clinical trials to work with researchers to determine the benefits of treatments. Success stories with gene therapies in blood diseases were cited as proof of concept where treatments being evaluated in clinical trials are demonstrating a significant and sustained impact on diseases. Evidence of benefit is needed by both regulatory bodies that approve the treatments, such as the FDA, and by public and private payers / insurers that pay for treatments and patients that need to know the best option for their particular disease.

In addition, various speakers cited the continued proliferation of “unproven treatments” being marketed by for-profit centers. There was broad concern that the promotion of treatment where there is no evidence of effectiveness will mislead some patients and potentially harm the scientifically rigorous development of new treatments. Particularly for “stem cell” treatments, there was a desire to develop evaluation criteria that are clear and transparent to allow legitimate treatments to be distinguished from those with no evidence of effectiveness. One participant suggested there be a scorecard approach where specific treatments could be rated against specific indicators of safety, medical benefit and value in relation to alternative treatments. The idea would be to make this information widely available to patients, medical providers and the public to inform everything from medical decision making to advertising.

Communicating the Vision

The final session considered communication needs for the field of regenerative medicine. Patients and patient advocacy organizations described how they are using social media and other networking tools to share information and experiences in navigating their treatment options. Patient advocacy groups also described the challenges from providers of unproven treatments. In one case, a for profit “pop up” clinic had used the group’s videos in an attempt to legitimize their unproven treatment.

There was general consensus among the panelists that the field of regenerative medicine needs “trusted intermediaries” who can evaluate claims and help patients distinguish between high quality research and “snake oil”. These intermediaries should have the capacity to compile the most reliable evidence and utilize it to determine what options are available to patients. In addition, there needs to be shared decision making model where patients have the opportunity to explore options in an unbiased environment so they may make the best decision based on their specific needs and values.

Creating this kind of Navigation System will not be easy but the alternative is unacceptable. Too many vulnerable patients are being taken advantage of by the growing number of “predatory clinics” hawking expensive therapies that are both unproven and unapproved. We owe it to these patients to create a simple way for them to identify what are the most promising therapies, ones that have the highest chance of being both safe and effective. The roundtable discussion marked a starting point, bringing together many of the key players in the field, highlighting the key issues and beginning to identify possible solutions.

It’s official: the state of regenerative medicine is strong

A panel discussion to a packed house at the annual ARM State of the Industry briefing

Calling it a “year of dramatic impact for patients” Janet Lambert, the CEO of the Alliance for Regenerative Medicine (ARM), gave the annual “State of the Industry” briefing today in San Francisco.

The briefing is a traditional kick-off event to mark JP Morgan week in the City, a time when hotel rooms go for $1,000 a night and just reserving a table in the lobby for meetings can set you back hundreds of dollars. Fortunately, the ARM briefing is free. And worth every penny.

Janet Lambert, CEO Alliance for Regenerative Medicine

Lambert ran down the numbers that highlighted how the field is growing and expanding:

  • 987 companies world wide – most of those in the US
  • 1,000 + clinical trials
  • $9.8 billion in revenue/investments

Saying “for many of these patients these therapies don’t just bring improvements, they bring dramatic improvements” Lambert pointed out that when those 1,000 clinical trials are fully enrolled it will mean 60,000 patients getting stem cell and gene therapies. She says it’s estimated that in the coming years around half a million patients in the US alone will get one of those therapies.

More and more of the clinical trials are at advanced stages:

  • 100 Phase 3
  • 591 Phase 2
  • 381 Phase 1

The biggest sector for clinical trials is cancer, but there are also substantial numbers for central nervous system therapies, muscular skeletal and even rare diseases.

Lambert said there are two key issues facing the field in the coming year. One is improving the industry’s manufacturing capability to ensure we are able to produce the cells needed to treat large numbers of patients. As evidence she cited the fact that Pfizer and Novartis are investing hundreds of millions of dollars in in-house manufacturing facilities. 

The second key issue is reimbursement, so that companies can get paid for delivering those treatments to patients.  “There is appetite and interest in this from people around the world, but right now most conversations about reimbursement are taking place one at a time. We haven’t yet evolved to the point where we have standard models to help get products to market and help them be commercially successful.”

The forecast for the year ahead? “Sunny with some clouds. 2019 was a year of significant growth and we enter 2020 with hopes of continued expansion, as we look to grow the impact on patients.” 

The podcast that sounds like a science thriller but for the patients involved is all too real

Laura Beil, writer and producer of the Bad Batch podcast

As we get close to the end of the year there is no shortage of lists of the “best of the year” and even this year the “best of the decade”. But when it comes to podcasts it would be hard to think of a better one than “Bad Batch”. It’s part stem cell research, part medical mystery and altogether engrossing.

It’s the work of Laura Beil, an award-winning journalist who follows the trail of a stem cell therapy that was supposed to help patients but instead left them battling life-threatening infections. It highlights how some clinics are able to find loopholes in the law that allow them to offer unproven and unapproved therapies, and how those therapies can put people’s lives at risk.

We have written about the dangers of predatory stem cell clinics several times, but in “Bad Batch” you get to hear the voices of the people affected, and ultimately the people responsible. It’s great journalism and fascinating story telling. And it’s a reminder of the work that needs to be done to stop this ever happening again.