Collaborative Funding Partnerships

Creating a ‘bespoke’ approach to rare diseases

/ Kevin McCormack / 2 Comments

THIS BLOG IS ALSO AVAILABLE AS AN AUDIO CAST

Up until recently the word “bespoke” meant just one thing to me, a hand-made suit, customized and fitted to you. There’s a street in London, Saville Row, that specializes in these suits. They’re gorgeous. They’re also very expensive and so I thought I’d never have a bespoke anything.

I was wrong. Because CIRM is now part of a bespoke arrangement. It has nothing to do with suits, it’s far more important than that. This bespoke group is aiming to create tailor-made gene therapies for rare diseases.

It’s called the Bespoke Gene Therapy Consortium (BGTC). Before we go any further I should warn you there’s a lot of acronyms heading your way. The BGTC is part of the Accelerating Medicines Partnership® (AMP®) program. This is a public-private partnership between the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), and multiple public and private organizations, such as CIRM.

The program is managed by the Foundation for the NIH (FNIH) and it aims to develop platforms and standards that will speed the development and delivery of customized or ‘bespoke’ gene therapies that could treat the millions of people affected by rare diseases.

Why is it necessary? Well, it’s estimated that there are around 7,000 rare diseases and these affect between 25-30 million Americans. Some of these diseases affect only a few hundred, or even a few dozen people. With so few people they almost always struggle to raise the funds needed to do research to find an effective therapy. However, many of these rare diseases are linked to a mutation or defect in a single gene, which means they could potentially be treated by highly customizable, “bespoke” gene therapy approaches.

Right now, individual disease programs tend to try individual approaches to developing a treatment. That’s time consuming and expensive. The newly formed BGTC believes that if we create a standardized approach, we could develop a template that can be widely used to develop bespoke gene therapies quickly, more efficiently and less expensively for a wide array of rare diseases.

“At CIRM we have funded several projects using gene therapy to help treat, and even cure, people with rare diseases such as severe combined immunodeficiency,” says Dr. Maria T. Millan, the President and CEO of CIRM. “But even an agency with our resources can only do so much. This agreement with the Bespoke Gene Therapy Consortium will enable us to be part of a bigger partnership, one that can advance the field, overcome obstacles and lead to breakthroughs for many rare diseases.”

With gene therapy the goal is to identify the genetic defect that is causing the disease and then deliver a normal copy of the gene to the right tissues and organs in the body, replacing or correcting the mutation that caused the problem. But what is the best way to deliver that gene? 

The BGTC’s is focusing on using an adeno-associated virus (AAV) as a delivery vehicle. This approach has already proven effective in Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), and spinal muscular atrophy. The consortium will test several different approaches using AAV gene therapies starting with basic research and supporting those all the way to clinical trials. The knowledge gained from this collaborative approach, including developing ways to manufacture these AAVs and creating a standard regulatory approach, will help build a template that can then be used for other rare diseases to copy.

As part of the consortium CIRM will identify specific rare disease gene therapy research programs in California that are eligible to be part of the AMP BGTC. CIRM funding can then support the IND-enabling research, manufacturing and clinical trial activities of these programs.

“This knowledge network/consortium model fits in perfectly with our mission of accelerating transformative regenerative medicine treatments to a diverse California and world,” says Dr. Millan. “It is impossible for small, often isolated, groups of patients around the world to fund research that will help them. But pooling our resources, our skills and knowledge with the consortium means the work we support here may ultimately benefit people everywhere.”

IBSC directors bring in nearly $12 million to fund the future of bimolecular research at UC Santa Cruz

/ Katie Sharify / 1 Comment

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Left to right: Lindsay Hinck and Camilla Forsberg

UC Santa Cruz professors Camilla Forsberg and Lindsay Hinck are not only pushing boundaries in their field as the female-led program directors of the Institute for the Biology of Stem Cells (IBSC), they’ve also been looking for ways to enhance the environment within the academic research infrastructure.

“We really wanted to make an effort to elevate everyone’s capacity for doing more research,” explains Forsberg. It was this drive that led the researchers to focus on bringing in grants to support students at different stages of their education to participate in research training programs.

So far, Fosberg and Hinck’s efforts have provided nearly $12 million in extramural funding for predoctoral and undergraduate training programs. The California Institute for Regenerative Medicine (CIRM), which provides graduate and postdoctoral funding, is one of the five funding institutions that have supported IBSC. This funding will shape the future of the IBSC, which brings together more than 30 laboratories across the Engineering and Physical and Biological Sciences divisions, as well as the Science & Justice Research Center.

“We didn’t set out to have five training programs, but then there were more opportunities, so we kept pitching our basic mentoring philosophies to different funders,” Forsberg said. “Now we have five different programs. I guess we found a secret sauce that made our funders excited.”

Forsberg and Hinck’s secret sauce is perhaps in part due to their devotion to forming strong peer connections amongst a group of talented graduate and postdoctoral researchers. The programs aim to connect cohorts of trainees who can interact and network through the IBSC in order to form a peer support ecosystem.

Additionally, IBSC strives to build cohorts that welcome and foster diverse perspectives as they will host an upcoming pilot program that aims to demystify the lengthy path from academia to a research career.

With their lastest $1 million training grant from the National Institute of Child Health and Human Development (NICHD), Forsberg and Hinck hope to provide support for postdoctoral scholars interested in the biotech industry. So far, biotech companies Jasper Therapeutics and Roche have joined the collaborative effort with IBSC to create shadowing opportunities for trainees to learn outside of the academic environment.

Furthermore, pre and postdoctoral trainees supported by these training grants can be hosted by several labs in the IBSC and beyond.

“The key thing about all these training programs is that they implement new ideas about structured graduate and postdoctoral training,” Hinck said. “While getting a training grant position is competitive, we try to make the structured training provided by the grants widely available so that all graduate students and postdoctoral scholars at UCSC can increase their skill sets. The environment that’s built around these training programs elevates opportunities for everyone.”

Read the full release here.

A Match Made in Heaven, if heaven were in Oakland!

/ Kevin McCormack / Leave a comment
The Matchmaker – by Gerrit van Honthorst

Throughout history, matchmakers have played an important role in bringing together couples for arranged marriages. Fast forward to today and CIRM is now playing a similar role. We’re not looking to get anyone hitched, what we are trying to do is create partnerships between people we are funding and companies looking for the next hot thing.

So far, I’d say we are doing a pretty decent job. Over the years we have leveraged our funding to bring in some $13 billion in additional investments in stem cell research. But there’s still a lot of untapped potential out there. That’s why tomorrow, March 9th, we’re joining with BIOCOM to host a Partner Day.

The idea is to highlight some of the most promising programs we are funding and see if we can find partners for them, partners who want to help advance the research and ultimately – we hope – bring those therapies to patients.

The webinar and panel discussion will feature a presentation from the CIRM Business Development team about our portfolio. That’s a pretty extensive list because it covers all stages of research from Discovery or basic, through Translational and all the way to Clinical. We’ll show how our early investment in these programs has helped de-risk them and given them the chance to get the data needed to demonstrate their promise and potential.

So, who are we interested in having join us? Pretty nearly everyone involved in the field:

  • Academic institutions
  • Research organizations
  • Entrepreneurs
  • Venture capital firms
  • Companies

And the areas of interest are equally broad:

  • Stem or progenitor cell-based therapy
  • Cell Therapy
  • Gene therapy
  • Biologic
  • Small molecule
  • Medical Device
  • Diagnostic
  • Tools/Tech
  • Other

And for those who are really interested and don’t want to waste any time, there’s an opportunity to set up one-on-one meetings right away. After all, if you have found the perfect match, why wait!

But here’s the catch. Space is limited so you need to register ahead. Here’s where you go to find out all the details and sign up for the event.

A model for success

/ Kevin McCormack / Leave a comment
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.

Charting a new course for stem cell research

/ Kevin McCormack / 1 Comment

What are the latest advances in stem cell research targeting cancer? Can stem cells help people battling COVID-19 or even help develop a vaccine to stop the virus? What are researchers and the scientific community doing to help address the unmet medical needs of underserved communities? Those are just a few of the topics being discussed at the Annual CIRM Alpha Stem Cell Clinic Network Symposium on Thursday, October 8th from 9am to 1.30pm PDT.

Like pretty nearly everything these days the symposium is going to be a virtual event, so you can watch it from the comfort of your own home on a phone or laptop. And it’s free.

The CIRM Alpha Clinics are a network of leading medical centers here in California. They specialize in delivering stem cell and gene therapies to patients. So, while many conferences look at the promise of stem cell therapies, here we deal with the reality; what’s in the clinic, what’s working, what do we need to do to help get these therapies to patients in need?

It’s a relatively short meeting, with short presentations, but that doesn’t mean it will be short on content. Some of the best stem cell researchers in the U.S. are taking part so you’ll learn an awful lot in a short time.

We’ll hear what’s being done to find therapies for

  • Rare diseases that affect children
  • Type 1 diabetes
  • HIV/AIDS
  • Glioblastoma
  • Multiple myeloma

We’ll discuss how to create a patient navigation system that can address social and economic determinants that impact patient participation? And we’ll look at ways that the Alpha Clinic Network can partner with community care givers around California to increase patient access to the latest therapies.

It’s going to be a fascinating day. And did I mention it’s free!

All you have to do is go to this Eventbrite page to register.

And feel free to share this with your family, friends or anyone you think might be interested.

We look forward to seeing you there.

CIRM & CZI & MOU for COVID-19

/ Kevin McCormack / Leave a comment

Too many acronyms? Not to worry. It is all perfectly clear in the news release we just sent out about this.

A new collaboration between the California Institute for Regenerative Medicine (CIRM) and the Chan Zuckerberg Initiative (CZI) will advance scientific efforts to respond to the COVID-19 pandemic by collaborating on disseminating single-cell research that scientists can use to better understand the SARS-CoV-2 virus and help develop treatments and cures.

CIRM and CZI have signed a Memorandum of Understanding (MOU) that will combine CIRM’s infrastructure and data collection and analysis tools with CZI’s technology expertise. It will enable CIRM researchers studying COVID-19 to easily share their data with the broader research community via CZI’s cellxgene tool, which allows scientists to explore and visualize measurements of how the virus impacts cell function at a single-cell level. CZI recently launched a new version of cellxgene and is supporting the single-cell biology community by sharing COVID-19 data, compiled by the global Human Cell Atlas effort and other related efforts, in an interactive and scalable way.

“We are pleased to be able to enter into this partnership with CZI,” said Dr. Maria T. Millan, CIRM’s President & CEO. “This MOU will allow us to leverage our respective investments in genomics science in the fight against COVID-19. CIRM has a long-standing commitment to generation and sharing of sequencing and genomic data from a wide variety of projects. That’s why we created the CIRM genomics award and invested in the Stem Cell Hub at the University of California, Santa Cruz, which will process the large complex datasets in this collaboration.”  

“Quickly sharing scientific data about COVID-19 is vital for researchers to build on each other’s work and accelerate progress towards understanding and treating a complex disease,” said CZI Single-Cell Biology Program Officer Jonah Cool. “We’re excited to partner with CIRM to help more researchers efficiently share and analyze single-cell data through CZI’s cellxgene platform.”

In March 2020, the CIRM Board approved $5 million in emergency funding to target COVID-19. To date, CIRM has funded 17 projects, some of which are studying how the SARS-CoV-2 virus impacts cell function at the single-cell level.

Three of CIRM’s early-stage COVID-19 research projects will plan to participate in this collaborative partnership by sharing data and analysis on cellxgene.   

  • Dr. Evan Snyder and his team at Sanford Burnham Prebys Medical Discovery Institute are using 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 treating the virus.
  • Dr. Brigitte Gomperts at UCLA is studying a lung organoid model made from human stem cells in order to identify drugs that can reduce the number of infected cells and prevent damage in the lungs of patients with COVID-19.
  • Dr. Justin Ichida at the University of Southern California is trying to determine if a drug called a kinase inhibitor can protect stem cells in the lungs and other organs, which the novel coronavirus selectively infects and kills.

“Cumulative data into how SARS-CoV-2 affects people is so powerful to fight the COVID-19 pandemic,” said Stephen Lin, PhD, the Senior CIRM Science Officer who helped develop the MOU. “We are grateful that the researchers are committed to sharing their genomic data with other researchers to help advance the field and improve our understanding of the virus.”

CZI also supports five distinct projects studying how COVID-19 progresses in patients at the level of individual cells and tissues. This work will generate some of the first single-cell biology datasets from donors infected by SARS-CoV-2 and provide critical insights into how the virus infects humans, which cell types are involved, and how the disease progresses. All data generated by these grants will quickly be made available to the scientific community via open access datasets and portals, including CZI’s cellxgene tool.

Super stem cell exhibit opens in San Diego

/ Kevin McCormack / Leave a comment

Stem cell exhibit

The best science museums are like playgrounds. They allow you to wander around, reading, watching and learning and being amazed as you go. It’s not just a feast for the mind; it’s also fun for the hands.  You get to interact with and experience science, pushing buttons, pulling levers, watching balls drop and electricity spark.

The best science museums bring out the kid in all of us.

This Saturday a really great science museum is going to be host to a really great exhibition. The Reuben H. Fleet Science Center in San Diego is the first stop on a California tour for “Super Cells: The Power of Stem Cells”. The exhibit is coming here fresh from a successful tour of Canada and the UK.

The exhibit is a “hands-on” educational display that demonstrates the importance and the power of stem cells, calling them “our body’s master cells.” It uses animations, touch-screen displays, videos and stunning images to engage the eyes and delight the brain.

stem cell exhibit 2Each of the four sections focuses on a different aspect of stem cell research, from basic explanations about what a stem cell is, to how they change and become all the different cells in our body. It has a mini laboratory so visitors can see how research is done; it even has a “treatment” game where you get to implant and grow cells in the eye, to see if you can restore sight to someone who is blind.

 

In a news release the Fleet Science Center celebrated the role that stem cells play in our lives:

“Stem cells are important because each of us is the result of only a handful of tiny stem cells that multiply to produce the 200 different types of specialized cells that exist in our body. Our stem cells continue to be active our whole lives to keep us healthy. Without them we couldn’t survive for more than three hours!”

It is, in short, really fun and really cool.

Of course we might be a tad biased here as we helped produce and develop the exhibit in collaboration with the Sherbrooke Museum of Science and Nature in Canada, the Canadian Stem Cell Network, the Centre for Commercialization of Regenerative Medicine in Canada; the Cell Therapy Catapult in the UK, and EuroStemCell.

stem cell exhibit 3

The exhibit is tri-lingual (English, Spanish and French) because our goal was to create a multi-lingual global public education program. San Diego was an obvious choice for the first stop on the California tour (with LA and the Bay Area to follow) because it is one of the leading stem cell research hubs in the U.S., and a region where CIRM has invested almost $380 million over the last ten years.

As our CIRM Board Chair, Jonathan Thomas, said:

“One of our goals at CIRM is to help spread awareness for the importance of stem cell research. San Diego is an epicenter of stem cell science and having this exhibition displayed at the Reuben H. Fleet Science Center is a wonderful opportunity to engage curious science learners of all ages.”

The Super Cells exhibit runs from January 23 to May 1, 2016, in the Main Gallery of the Reuben H. Fleet Science Center. The exhibition is included with the cost of Fleet admission.

For more information, visit the Reuben H. Fleet Science Center website.

Roadmap to our epigenome reveals the genetic switches that make one adult cell type different from others

/ Don Gibbons / 2 Comments

A decade ago scientists made a huge news splash when they announced the completion of the human genome project declaring it the first road map of our genes. But it did not take long to realize that the early road map was like some of the early days of GPS systems: it lacked knowledge of many on-ramps, off-ramps and one-way streets.

Today, the scientific world announced a massive fix to its genetic GPS. While all of our cells carry the same genes, their function varies wildly based one which genes are turned off, which are turned on, and even which are turned on in a hyper active way. Complex chemical and structural changes in the chromosomes that house our genes—collectively called the epigenome—determine that activity.

This video from Nature explaining the epigenome with music metaphors is linked in the last paragraph.

This video from Nature explains the epigenome with music metaphors.


A massive project, mostly funded by the National Institutes of Health through a consortium of research teams around the country, published a series of papers today in Nature. The Roadmap Epigenomic Consortium did extensive analysis of 111 epigenomes from different types of cells: normal heart tissue and immune cells, for example, as well as cells from patients with diseases such as neurons from patients with Alzheimer’s. The Scientist this morning quoted one member of the Consortium, MIT’s Manolis Kellis:

“The human epigenome is this collection of . . . chemical modifications on the DNA itself and on the packaging that holds DNA together. All our cells have a copy of the same book, but they’re all reading different chapters, bookmarking different pages, and highlighting different paragraphs and words.”

CIRM funding contributed to two of the papers authored by a team at the University of California, San Diego. One of the papers looked at how the genetic structure of stem cells changes as they mature and differentiate into specific types of adult tissue. The other looked at how structural differences determine which of the chromosomes we inherit—the one from mom or the one from dad—has a stronger influence on specific traits. The senior author on the studies, Bing Ren, noted in a university press release that these differences will be important as we think about individualizing therapies:

“Both of these studies provide important considerations for clinicians and researchers who are developing personalized medicines based on a patient’s genomic information”

The consortium’s publications today resulted from a massive data analysis. A press release from the Broad Institute in Cambridge, Massachusetts, describes the effort that required grouping two million predicted areas of change in the chromosomes into 200 sets or modules and then looking for how those modules impacted different cell types.

But if you are still having trouble understanding the concept of the epigenome, I highly recommend taking the five minutes it takes to watch this video produced by Nature. It equates the process to a symphony and what occurs when you change notes and intensity in the score.

How partnering with someone half way around the world could help develop new treatments here in California

/ Kevin McCormack / Leave a comment

Much as we love California, and we really do, even we have to admit that genius knows no boundaries and that great scientific research is taking place all over the world. As our goal as an agency is to accelerate the development of successful therapies for people in need it only makes sense that we would try and tap into that genius, wherever it is, in whatever way we can. That’s where our Collaborative Funding Partnership (CFP) program comes in.

Michel Hivert, Executive Director at MATIMOP (L) and ICOC Chairman Jonathan Thomas

Michel Hivert, Executive Director at MATIMOP (L) and ICOC Chairman Jonathan Thomas

Under Proposition 71, the voter-approved initiative that created the stem cell agency, all the research we fund has to be in California. But that doesn’t mean we can’t help create collaborations between researchers here – that we fund – and researchers in other parts of the world who get funding from other sources. And we do just that. In fact we now have 24 CFPs stretching from New York state to Brazil, Japan, the UK and Australia.

And now we have added two more. One with Poland two weeks ago  and today, with Israel. As the Chair of our governing Board, Jonathan Thomas said in a news release , the goal of these agreements is simple, to advance stem cell research around the world:

“Israel has long had a robust stem cell research community. Through this newly announced collaboration, we hope to generate partnerships between Israeli and California scientists that build on our complementary strengths and generate joint research projects that will benefit patients everywhere.”

Dr. Andy David, Consul General of Israel to the Pacific North West, echoed those sentiments:

“It represents a practical expression of shared interests that is unusual for its depth and range. Israel and California are on opposite corners of the globe geographically, but they are practically coming closer every day. The reason for this thriving relationship is the understanding that we are strong mutual assets.”

But nice as these partnerships are the only questions that really matter are do these collaborations really make a difference; do they really help increase the likelihood of a successful therapy? The answer from our experience is yes. For example, a team we are funding at Stanford is collaborating with a team from the Medical Research Council in the UK, focused on solid tumor cancers. The Stanford team has been given approval by the Food and Drug Administration (FDA) to run a clinical trial testing this approach on solid tumors, while the UK team is using the same approach to tackling acute myeloid leukemia (AML) an often-fatal cancer of the blood and bone marrow. Knowledge gained from one trial may well benefit the other and could ultimately lead to approaches to treating other solid tumor cancers such as breast, ovarian, bladder and colon.

Disease does not stop at the border and we see no reason for our engagement with the best science, and the best scientists, to stop there either. Our goal is to find cures, and we’ll go wherever we have to and work with whoever we can to meet that goal.