Proposition 71

Early CIRM support helps stem cell pioneer develop promising new therapy for cancer

/ Kevin McCormack / Leave a comment
Irv Weissman

Irv Weissman, Ph.D., Photo: courtesy Stanford University

When you get praise from someone who has been elected to the National Academy of Sciences and has been named California Scientist of the Year you know you must be doing something right.

That’s how we felt the other day when Irv Weissman, Director of the Stanford Institute of Stem Cell Biology and Regenerative Medicine, issued a statement about how important the support of CIRM was in advancing his research.

The context was the recent initial public offering (IPO) of Forty Seven Inc.. a company co-founded by Dr. Weissman. That IPO followed news that two Phase 2 clinical trials being run by Forty Seven Inc. were demonstrating promising results against hard-to-treat cancers.

Dr. Weissman says the therapies used a combination of two monoclonal antibodies, 5F9 from Forty Seven Inc. and Rituximab (an already FDA-approved treatment for cancer and rheumatoid arthritis) which:

“Led to about a 50% overall remission rate when used on patients who had relapsed, multi-site disease refractory to rituximab-plus-chemotherapy. Most of those patients have shown a complete remission, although it’s too early to tell if this is complete for life.”

5F9 attacks a molecule called CD47 that appears on the surface of cancer cells. Dr. Weissman calls CD47 a “don’t eat me signal” that protects the cancer against the body’s own immune system. By blocking the action of CD47, 5F9 strips away that “don’t eat me signal” leaving the cancer vulnerable to the patient’s immune system. We have blogged about this work here and here.

The news from these trials is encouraging. But what was gratifying about Dr. Weissman’s statement is his generosity in sharing credit for the work with CIRM.

Here is what he wrote:

“What is unusual about Forty Seven is that not only the discovery, but its entire preclinical development and testing of toxicity, etc. as well as filing two Investigational New Drug [IND] applications to the Food and Drug Administration (FDA) in the US and to the MHRA in the UK, as well as much of the Phase 1 trials were carried out by a Stanford team led by two of the discoverers, Ravi Majeti and Irving Weissman at Stanford, and not at a company.

The major support came from the California Institute of Regenerative Medicine [CIRM], funded by Proposition 71, as well as the Ludwig Cancer Research Foundation at the Ludwig Center for Cancer Stem Cell Research at Stanford. CIRM will share in downstream royalties coming to Stanford as part of the agreement for funding this development.

This part of the state initiative, Proposition 71, is highly innovative and allows the discoverers of a field to guide its early phases rather than licensing it to a biotech or a pharmaceutical company before the value and safety of the discovery are sufficiently mature to be known. Most therapies at early-stage biotechs are lost in what is called the ‘valley of death’, wherein funding is very difficult to raise; many times the failure can be attributed to losing the expertise of the discoverers of the field.”

Dr. Weissman also had praise for CIRM’s funding model which requires companies that produce successful, profitable therapies – thanks to CIRM support – to return a portion of those profits to California. Most other funding agencies don’t have those requirements.

“US federal funds, from agencies such as the National Institutes of Health (NIH) similarly support discovery but cannot fund more than a few projects to, and through, early phase clinical trials. And, under the Bayh-Dole Act, the universities keep all of the equity and royalties derived from licensing discoveries. In that model no money flows back to the agency (or the public), and nearly a decade of level or less than level funding (at the national level) has severely reduced academic research. So this experiment of funding (the NIH or the CIRM model) is now entering into the phase that the public will find out which model is best for bringing new discoveries and new companies to the US and its research and clinical trials community.”

We have been funding Dr. Weissman’s work since 2006. In fact, he was one of the first recipients of CIRM funding.  It’s starting to look like a very good investment indeed.

 

Emotions and gratitude at changing of the guard at Stem Cell Agency

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RandyFarewellFamily

Randy Mills and his family

Randy, as regular readers of this blog know, is, or rather was, the President and CEO of CIRM. James Harrison is less well known to the outside world but his imprint on CIRM, as our General Counsel and one of the key figures behind Proposition 71, is even bigger than that of Randy’s.

Randy came to the stem cell agency a little over three years ago and in pretty quick order completely refashioned us. Under his guidance CIRM 2.0 became a sleek, streamlined funding machine, turning what had been an almost two-year process from application to funding into one that took just 120 days. He revamped the frequency with which we offered specific programs, making it more predictable and so easier for researchers to know when the next round was coming up. He helped usher in a new Strategic Plan that is a blueprint for us until 2020.

But the changes he implemented were not just about the way we worked, it was also about how we worked and particularly how we worked together. He turned the agency into a true team, one where everyone felt they not only had a role to play but that what they did was important in determining the success of the agency.

Not surprisingly there was no shortage of people ready to praise him. CIRM Board Chair Jonathan Thomas (JT) thanked Randy for turning the agency around, transforming it into an organization that even the National Institutes of Health (NIH) now looks to as a model (more on that in a subsequent blog). Vice Chair Art Torres thanked Randy for his leadership and for his compassion toward patients, always putting them first in everything that he and the agency did. Board member Sherry Lansing called Randy “a genius and visionary”.

But perhaps the most moving tributes came from patients advocates.

Don Reed said; “When I first met Randy I didn’t like him. I thought CIRM was one of the best, if not the best, organization out there and who was this person to say they were going to come in and make it better. Well, you did Randy and we are all so very grateful to you for that.”

Adrienne Shapiro from Axis Advocacy, an organization dedicated to finding a cure for sickle cell disease, presented Randy with the “Heart of a Mother” award, thanking him for his tireless support of patients and their families.

Jake Javier, a participant in the Asterias spinal cord injury trial, wrote a note saying: “You positively affect so many through your amazing funding efforts for life changing research, and should be very proud of that. But something I will always remember is how personal and genuine you were while doing it. I hope you got the chance to meet as many of the people you helped as possible because I know they would remember the same.”

Randy – who is leaving to become President/CEO of the National Marrow Donor/Be The Match program – was clearly deeply moved by the tributes, but reminded everyone that he was leaving us in good hands. The Board named Dr. Maria Millan as the interim President and CEO, pending a meeting of a search committee to determine the steps for appointing a permanent replacement.

Randy praised Maria for her intelligence, compassion and vision:

“Maria Millan has been a great partner in all that we have achieved at CIRM. She was a key part of developing the Strategic Plan; she  understands it inside out and has been responsible for administering it. She is a wonderful leader and is going to be absolutely phenomenal.”

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James Harrison (left) with CIRM Board members Jonathan Thomas and Bert Lubin

The tributes for James Harrison were ever bit as moving. James has been a part of CIRM since before there was a CIRM. He helped draft Proposition 71, the ballot initiative that created the stem cell agency, and has played a key role since as General Counsel.

JT: “James has been a part of literally every decision and move that CIRM has made in its entire history. He’s been integral in everything. When I first came to CIRM, I was told by Bob Klein (JT’s predecessor as Chair) ‘Don’t brush your teeth without checking with James first’ suggesting a level of knowledge and expertise that was admirable.”

Jeff Sheehy “We would not be here without James. He organized the defense when we were sued by our opponents in the early days, through the various leadership challenges we had, all of the legal difficulties we had James was there to guide us and it’s been nothing short of extraordinary. Your brilliance and steadiness is amazing. While we are screaming and pulling our hair out there was James. Just saying his name makes me feel more relaxed.”

Sherry Lansing: “One thing I never worried about was our ethics, because you protected us at all times. You have such strong ethical values, you are always calm and rational and no matter what was going on you were always the rock who could explain things to everyone and deal with it with integrity.”

James is leaving to take a more active role in the law firm Remcho, Johansen & Purcell, where he is partner. Succeeding him as General Counsel is Scott Tocher, who has been at CIRM almost as long as James.

Randy; “To have someone like Scott come in and replace someone who wrote Proposition 71 speaks for the bench strength of the agency and how we are in very good hands.”

Art Torres joked “Scott has been waiting as long as Prince Charles has to take over the reins and we’re delighted to be able to work with him.”

We wish Randy and James great good luck in their next adventures.

 

Stem cell stories that caught our eye: turning on T cells; fixing our brains; progress and trends in stem cells; and one young man’s journey to recover from a devastating injury

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Healthy_Human_T_Cell

A healthy T cell

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Directing the creation of T cells. To paraphrase the GOP Presidential nominee, any sane person LOVES, LOVES LOVES their T cells, in a HUGE way, so HUGE. They scamper around the body getting rid of viruses and the tiny cancers we all have in us all the time. A CIRM-funded team at CalTech has worked out the steps our genetic machinery must take to make more of them, a first step in letting physicians turn up the action of our immune systems.

We have known for some time the identity of the genetic switch that is the last, critical step in turning blood stem cells into T cells, but nothing in our body is as simple as a single on-off event. The Caltech team isolated four genetic factors in the path leading to that main switch and, somewhat unsuspected, they found out those four steps had to be activated sequentially, not all at the same time. They discovered the path by engineering mouse cells so that the main T cell switch, Bcl11b, glows under a microscope when it is turned on.

“We identify the contributions of four regulators of Bcl11b, which are all needed for its activation but carry out surprisingly different functions in enabling the gene to be turned on,” said Ellen Rothenberg, the senior author in a university press release picked up by Innovations Report. “It’s interesting–the gene still needs the full quorum of transcription factors, but we now find that it also needs them to work in the right order.”

Video primer on stem cells in the brain.  In conjunction with an article in its August issue, Scientific American posted a video from the Brain Forum in Switzerland of Elena Cattaneo of the University of Milan explaining the basics of adult versus pluripotent stem cells, and in particular how we are thinking about using them to repair diseases in the brain.

The 20-minute talk gives a brief review of pioneers who “stood alone in unmarked territory.” She asks how can stem cells be so powerful; and answers by saying they have lots of secrets and those secrets are what stem cell scientist like her are working to unravel.  She notes stem cells have never seen a brain, but if you show them a few factors they can become specialized nerves. After discussing collaborations in Europe to grow replacement dopamine neurons for Parkinson’s disease, she went on to describe her own effort to do the same thing in Huntington’s disease, but in this case create the striatal nerves lost in that disease.

The video closes with a discussion of how basic stem cell research can answer evolutionary questions, in particular how genetic changes allowed higher organisms to develop more complex nervous systems.

kelley and kent

CIRM Science Officers Kelly Shepard and Kent Fitzgerald

A stem cell review that hits close to home.  IEEE Pulse, a publication for scientists who mix engineering and medicine and biology, had one of their reporters interview two of our colleagues on CIRM’s science team. They asked senior science officers Kelly Shepard and Kent Fitzgerald to reflect on how the stem cell field has progressed based on their experience working to attract top researchers to apply for our grants and watching our panel of outside reviewers select the top 20 to 30 percent of each set of applicants.

One of the biggest changes has been a move from animal stem cell models to work with human stem cells, and because of CIRM’s dedicated and sustained funding through the voter initiative Proposition 71, California scientists have led the way in this change. Kelly described examples of how mouse and human systems are different and having data on human cells has been critical to moving toward therapies.

Kelly and Kent address several technology trends. They note how quickly stem cell scientists have wrapped their arms around the new trendy gene editing technology CRISPR and discuss ways it is being used in the field. They also discuss the important role of our recently developed ability to perform single cell analysis and other technologies like using vessels called exosomes that carry some of the same factors as stem cells without having to go through all the issues around transplanting whole cells.

“We’re really looking to move things from discovery to the clinic. CIRM has laid the foundation by establishing a good understanding of mechanistic biology and how stem cells work and is now taking the knowledge and applying it for the benefit of patients,” Kent said toward the end of the interview.

jake and family

Jake Javier and his family

Jake’s story: one young man’s journey to and through a stem cell transplant; As a former TV writer and producer I tend to be quite critical about the way TV news typically covers medical stories. But a recent story on KTVU, the Fox News affiliate here in the San Francisco Bay Area, showed how these stories can be done in a way that balances hope, and accuracy.

Reporter Julie Haener followed the story of Jake Javier – we have blogged about Jake before – a young man who broke his spine and was then given a stem cell transplant as part of the Asterias Biotherapeutics clinical trial that CIRM is funding.

It’s a touching story that highlights the difficulty treating these injuries, but also the hope that stem cell therapies holds out for people like Jake, and of course for his family too.

If you want to see how a TV story can be done well, this is a great example.

Taking stock: ten years of the stem cell agency, progress and promise for the future

/ Kevin McCormack / 1 Comment

Under some circumstances ten years can seem like a lifetime. But when lives are at stake, ten years can fly by in a flash.

Ten years ago the people of California created the stem cell agency when they overwhelmingly approved Proposition 71, giving us $3 billion to fund and support stem cell research in the state.

In 2004 stem cell science held enormous potential but the field was still quite young. Back then the biology of the cells was not well understood, and our ability to convert stem cells into other cell types for potential therapies was limited. Today, less than 8 years after we actually started funding research, we have ten projects that are expected to be approved for clinical trials by the end of the year, including work in heart disease and cancer, HIV/AIDS and diabetes. So clearly great progress has been made.

Dean Carmen Puliafito and the panel at the Tenth Anniversary event at USC

Dean Carmen Puliafito and the panel at the Tenth Anniversary event at USC

Yesterday we held an event at the University of Southern California (USC) to mark those ten years, to chart where we have come from, and to look to where we are going. It was a gathering of all those who have, as they say, skin in the game: researchers, patients and patient advocates.

The event was held at the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research. As Dr. Carmen Puliafito, Dean of USC’s Keck School of Medicine noted, without CIRM the building would not even exist.

“With this funding, our researchers, and researchers in 11 other facilities throughout the state, gained a dedicated space to hunt for cures for some of the most pernicious diseases in the world, including heart disease, stroke, cancer, diabetes, Alzheimer’s and Parkinson’s disease.”

Dr. Dhruv Sareen from Cedars-Sinai praised CIRM for creating a whole new industry in the state:

“What Silicon Valley has done for technology, CIRM is doing for stem cell research in California.”

One of the beneficiaries of that new industry has been ViaCyte, a San Diego-based company that is now in clinical trials with a small implantable device containing stem cell-derived cells to treat type 1 diabetes. ViaCyte’s Dr. Eugene Brandon said without CIRM none of that would have been possible.

“In 2008 it was extremely hard for a small biotech company to get funding for the kind of work we were doing. Without that support, without that funding from CIRM, I don’t know where this work would be today.”

As with everything we do, at the heart of it are the patients. Fred Lesikar says when he had a massive heart attack and woke up in the hospital his nurse told him about a measure they use to determine the scale of the attack. When he asked how big his attack had been, she replied, “I’ve never seen numbers that large before. Ever.”

Fred told of leaving the hospital a diminished person, unable to do most basic things because his heart had been so badly damaged. But after getting a stem cell-based therapy using his own heart cells he is now as active as ever, something he says doesn’t just affect him.

“It’s not just patients who benefit from these treatments, families do too. It changes the life of the patient, and the lives of all those around them. I feel like I’m back to normal and I’m so grateful for CIRM and Cedars-Sinai for helping me get here.”

The team behind that approach, based at Cedars-Sinai, is now in a much larger clinical trial and we are funding it.

The last word in the event was left to Bob Klein, who led the drive to get Proposition 71 passed and who was the agency’s first Chair. He said looking at what has happened in the last ten years: “it is beyond what I could have imagined.”

Bob noted that the field has not been without its challenges and problems to overcome, and that more challenges and problems almost certainly lie in the future:

“But the genius of the people of this state is reflected in their commitment to this cause, and we should all be eternally grateful for their vision in supporting research that will save and transform people’s lives.”

Ten at ten at the stem cell agency: sharing the good news about progress from the bench to the bedside

/ Kevin McCormack / Leave a comment

Ten years ago this month the voters of California overwhelmingly approved Proposition 71, creating the state’s stem cell agency, the California Institute for Regenerative Medicine, and providing $3 billion to fund stem cell research in California.

That money has helped make California a global leader in stem cell research and led to ten clinical trials that the stem cell agency is funding this year alone. Those include trials in heart disease, cancer, leukemia, diabetes, blindness, HIV/AIDS and sickle cell disease.

To hear how that work has had an impact on the lives of patients we are holding a media briefing to look at the tremendous progress that has been made, and to hear what the future holds.

When: Thursday, November 20th at 11am

Where: Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at the University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033

Who: Hear from patients who have benefited from stem cell therapies, the researchers who have done the work, and the key figures in the drive to make California the global leader in stem cell research

To listen in to the event by phone:

Call in: 866.528.2256  Participant code: 1594399

For more information contact: Kevin McCormack, Communications Director, CIRM kmccormack@cirm.ca.gov

Cell: 415-361-2903