Stem Cell Agency Board meeting now LIVE

MEETING NOTICE AND AGENDA
REGULAR MEETING OF THE
INDEPENDENT CITIZENS OVERSIGHT COMMITTEE
CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE AND
THE APPLICATION REVIEW SUBCOMMITTEE
Organized Pursuant To The
CALIFORNIA STEM CELL RESEARCH AND CURES ACT

Thursday, May 21, 2015
9:00 a.m.- 5:00 p.m.

Main Location

  • Claremont Hotel 41 Tunnel Road Berkeley, CA 94705

Other Locations

  • 10996 Torreyana Road, Suite 200 San Diego, CA 92121
  • University of California, Irvine 4125 Natural Sciences II  Irvine, CA 92697-1450
  • Cedars-Sinai Medical Center 8700 Beverly Blvd.  Davis 5090 Los Angeles, CA 90048
  • 40 Taylor St. Danbury, Conn.

Dial In Information
Dial in: (866) 320-4709
Access Code: 360431

Listen Online Only
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Conference ID#:  360431

WebEx Information

1. Go to https://cirm.webex.com/cirm/onstage/g.php?MTID=ed1777f2c2d2300f26215255e…
2. Click “Join Now”.

[Members of the Public will be invited to provide testimony before or during consideration of each item. Makers of public comments are asked to limit their testimony to three (3) minutes.]

REPORTS & DISCUSSION ITEMS

1. Call to Order.

2. Pledge of Allegiance.

3. Roll Call.

4. Chairman’s Report.

5. President’s Report. (PDF)

ACTION ITEMS

6. Consideration of rule of order authorizing a consent calendar. (PDF)

PROPOSED CONSENT CALENDAR ITEMS 7-9

7. Consideration of appointment of new scientific members to the Grants Working Group. (PDF)

8. Consideration of amendment to GWG bylaws. (PDF)

9. Consideration of minutes from the January and March ICOC Board meetings. (PDF)

ACTION ITEMS

10. Consideration of CIRM Budget for Fiscal Year 2015-2016. (PDF)

11. Consideration of amendment to Interim Grants Administration Policy for Clinical Stage Programs (PA 15-01, 15-02 and 15-03) to permit awardee to elect to treat its award as a loan.

12. Consideration of concept plan for CIRM Conference Grant program. (PDF)

13. Consideration of amendment to CIRM organization chart. (PDF)

14. Resolution honoring Patient Advocate Joan Samuelson. (PDF)

15. Consideration of applications submitted in response to PA 15-01 (Late Stage Pre-Clinical Projects) and 15-02 (Clinical Stage Projects).

CLOSED SESSION

16. Discussion of confidential intellectual property or work product, prepublication data, financial information, confidential scientific research or data, and other proprietary information relating to applications for PA 15-01 (Late Stage Pre-Clinical Projects) and 15-02 (Clinical Stage Projects) (Health & Safety Code 125290.30(f) (3) (B) and (C)).

DISCUSSION ITEMS

17. Presentation by Moss Adams regarding Performance Audit. (PDF)

18. Discussion of CIRM Strategic Plan. (PDF)

19. Public comment.  The Committee will accept public testimony on any matter under its jurisdiction that is not on the agenda, but the Committee cannot act on any such matter at this meeting.

THE ORDER OF BUSINESS MAY BE CHANGED WITHOUT NOTICE.

**NOTICE**

The California Institute for Regenerative Medicine and its Independent Citizens Oversight Committee, and any subcommittees thereof, comply with the Americans with Disabilities Act (ADA) by ensuring that the meeting facilities are accessible to persons with disabilities, and providing that this notice and information given to the Members of the Committee is available to the public in appropriate alternative formats when requested. If you need further assistance, including disability-related modifications or accommodations, you may contact Maria Bonneville at the California Institute for Regenerative Medicine at 415-396-9100 no later than the day prior to the meeting.

Questions or requests for additional information prior to the Independent Citizens Oversight Committee meeting may be referred to Maria Bonneville at the California Institute for Regenerative Medicine at mbonneville@cirm.ca.gov or 415-396-9100.

This meeting agenda is also available on the website for the California Institute for Regenerative Medicine at http://www.cirm.ca.gov.

Stem cells, Darth Vader and the high cost of hope and hype

Darth Vader: Photo by Stefano Buttafoco

Darth Vader: Photo by Stefano Buttafoco

It’s not very often that you get stories about stem cells that mention Darth Vader, Obi Wan Kenobi, the Pittsburgh Steelers and a Beverly Hills plastic surgeon, but those references all popped up in a recent flurry of articles that are shining – yet again – the light on many of the unproven, unregulated uses of stem cells to treat everything from arthritis to Parkinson’s disease.

Let’s start with an article by Associated Press (AP) writer Will Graves who digs into the use of stem cells in sports.  Graves does a good job of highlighting all the reasons why an athlete would try a stem cell therapy quoting Dr. Jim Bradley, a team physician with the Steelers:

“They want the cutting edge, anything that is cutting edge that can get their guys a couple more years in the league. If I was an agent, I’d want the same thing.”

But Graves also does a fine job of pointing out that these therapies are unproven, and that in many cases athletes go overseas to get them because those clinics do not have to meet the same strict regulations as clinics here in the US.

“Traveling to a place like the Caymans, that’s like saying ‘I’m going to Mexico to have an appendectomy to save $80,'” said Dr. Matthew Matava, head physician for the St. Louis Rams and the NHL’s St. Louis Blues. “It looks like it’s not very smart or you’re grasping at straws.”

He also quotes Dr. Freddie Fu, head physician for the University of Pittsburgh athletics program, saying there is far too much uncertainty to take risks. Fu says in many cases the people delivering the therapies don’t even know where these stem cells might go, or what they might do:

“You can have one cell be Obi Wan Kenobi, the other is Darth Vader. You’re not sure which way it’s going to go.”

Matthew Perrone starts his piece in the Huffington Post, with a paragraph that is both gripping and disgusting:

“The liquid is dark red, a mixture of fat and blood, and Dr. Mark Berman pumps it out of the patient’s backside. He treats it with a chemical, runs it through a processor — and injects it into the woman’s aching knees and elbows.”

Berman, the co-founder of the largest chain of stem cell clinics in the US, admits he doesn’t know what’s in the mixture he is injecting into patients. But he says it can help treat more than 30 different diseases and conditions from Lou Gehrig’s disease to lupus and even erectile dysfunction.

Perrone’s piece is a long, detailed and thoughtful look at the finances that drive this business and how many stem cell clinics charge as much as $9,000 for unproven therapies. He quotes UC Davis stem cell researcher – and CIRM grantee – Dr. Paul Knoepfler:

“It’s sort of this 21st century cutting-edge technology. But the way it’s being implemented at these clinics and how it’s regulated is more like the 19th century. It’s a Wild West.”

But the price tag at those US-based clinics is tiny compared to how much some people are paying at overseas facilities. Los Angeles Times reporter Alan Zarembo focuses on the case of William Rader and his company Stem Cell of America.

Rader, a psychiatrist, had his medical license revoked by the Medical Board of California citing negligence, false or misleading advertising and professional misconduct. The Board said: “His dishonesty permeates every aspect of his business and practices.”

Yet Rader continues to charge up to $30,000 for stem cell procedures at the clinic he runs in Mexico. He uses the same procedure for different conditions, offers no scientific evidence it works but claims he’s helped many people and even cured a patient of HIV/AIDS.

For patients battling life-threatening diseases and disorders it is easy to see why they would be willing to take a chance on a therapy, any therapy, that might save their life.

And that’s where the danger in all this lies. What might be seen by an athlete as something worth trying to see if it might help extend their career a year or two, for people at the other end of life this may be their last chance, and that vulnerability means they’ll pay whatever they have to, for something that may be of no benefit whatsoever.

Telling an athlete this might help them play longer is one thing. Playing on a patient’s life or death fears is entirely another.

For more information on how you can make an informed decision about whether a stem cell therapy is right for you, particularly one offered overseas, go to our page on stem cell tourism.

Taking a step back, to move forward

Progress doesn’t always come in straight lines. Particularly when you are a pioneer in a whole new field of medicine like stem cells where virtually everything you do is being done for the first time, and the therapies you are developing are going to be tested in people for the first time. That’s why everything you do has to be done with extra caution to make sure the best interests of the patients come first. Sometimes that means not rushing ahead, but pausing, while you decide what is the best approach.

SangamoThat’s what Sangamo have done in announcing they are delaying the start of their clinical trial in beta thalassemia – a trial we are funding.

They are taking what amounts to a “time-out” so that they can make a small change in direction, one they – and we – hope will ultimately prove most effective for patients.

Βeta thalassemia is a genetic disease that results in patients producing red blood cells with poorly functioning hemoglobin, the protein that carries oxygen to all our tissues. If not properly managed the condition can be fatal.

The approach Sangamo are taking to cure the problem involves using zinc finger nuclease (ZFN), a kind of molecular scissors, to genetically edit the patient’s own stem cells, correcting the problem and enabling them to produce healthy hemoglobin and healthy red blood cells.

But as they geared up for the clinical trial, one that was approved by the Food and Drug Administration (FDA), they did some preclinical testing and saw that an approach they were using on a similar disease – sickle cell disease (SCD) – appeared to be more efficient and effective at correcting the underlying genetic problem. Both used ZFN to edit the defective gene, but they both had slightly different targets on those genes. The one targeting SCD seemed to have some key advantages, so they have decided to switch to this approach for both conditions.

In a news release Edward Lanphier, Sangamo’s President and CEO, says it wasn’t an easy decision to make, but it is the right decision:

“While our joint decision will result in a delay in the initiation of the beta-thalassemia Phase 1 clinical trial, we believe that the efficiency of the consolidated development path and potential benefit to patients clearly support this decision.”

The next step is for Sangamo to go back to the FDA and file a new Investigational New Drug or IND application for this new approach to beta-thalassemia. They’re hopeful they’ll be able to get that approval, and move ahead with their clinical trial next year.

The good news is that thanks to our new way of funding under CIRM 2.0, Sangamo will have the opportunity to seek CIRM’s support for its work through both our preclinical program, as they make their changes, and then our clinical program if and when they get FDA approval to move ahead. This uninterrupted support is what CIRM 2.0 was set up to achieve, to move promising projects like this to patients as quickly as possible.

For the team at Sangamo it’s obviously disappointing to have to stop and change direction. It’s also disappointing for the patients hoping this would lead to a more effective therapy, even a cure.

But this is not a set back. Rather, it’s a step back. One that allows Sangamo to choose what they believe is a better option, one that will ultimately be much better for patients.

How stimulating! A new way to repair broken bones

For those of us who live in earthquake country the recent devastating quakes in Nepal are a reminder, as if we needed one, of the danger and damage these temblors can cause. Many of those injured in the quake suffered severe bone injuries – broken legs, crushed limbs etc. Repairing those injuries is going to take time and expert medical care. But now a new discovery is opening up the possibility of repairing injuries like this, even regenerating the broken bones, in a more efficient and effective way.

shutterstock_18578173A study published in Scientific Reports  shows that it is possible to regrow bone tissue using protein signals from stem cells. Even more importantly is that this new bone tissue seems to be just as effective, in terms of the quantity and quality of the bone created, as the current methods.

In a news release senior author Todd McDevitt, Ph.D., said this shows we might not even need whole stem cells to regenerate damaged tissue:

“This proof-of-principle work establishes a novel bone formation therapy that exploits the regenerative potential of stem cells. With this technique we can produce new tissue that is completely stem cell-derived and that performs similarly with the gold standard in the field.”

McDevitt – who is now at the Gladstone Institutes thanks to a research leadership award from CIRM  – extracted the proteins that stem cells produce to help regenerate damaged tissues. They then isolated the particular factors they needed to help regenerate bones, in this case bone morphogenetic protein or BMP. That BMP was then transplanted into mice to stimulate bone growth. And it worked.

While this compares favorably to current methods of regenerating or repairing damaged bones it has a few advantages. Current methods rely on getting bones from cadavers and grinding them up to get the growth factors needed to stimulate bone growth. But bones from cadavers can often be in short supply and the quality is highly variable.

As McDevitt says:

“These limitations motivate the need for more consistent and reproducible source material for tissue regeneration. As a renewable resource that is both scalable and consistent in manufacturing, pluripotent stem cells are an ideal solution.”

He says the next step is to build on this research, and try to find ways to make this method even more efficient. If he succeeds he says it could open up new ways of treating devastating injuries such as those sustained by soldiers in battle, or by earthquake victims.

A hopeful sight: therapy for vision loss cleared for clinical trial

Rosalinda Barrero

Rosalinda Barrero, has retinitis pigmentosa

Rosalinda Barrero says people often thought she was rude, or a snob, because of the way she behaved, pretending not to see them or ignoring them on the street. The truth is Rosalinda has retinitis pigmentosa (RP), a nasty disease, one that often attacks early in life and slowly destroys a person’s vision. Rosalinda’s eyes look normal but she can see almost nothing.

“I’ve lived my whole life with this. I told my daughters [as a child] I didn’t like to go Trick or Treating at Halloween because I couldn’t see. I’d trip; I’d loose my candy. I just wanted to stay home.”

Rosalinda says she desperately wants a treatment:

“Because I’m a mom and I would be so much a better mom if I could see. I could drive my daughters around. I want to do my part as a mom.”

Now a promising therapy for RP, funded by the stem cell agency, has been cleared by the Food and Drug Administration (FDA) to start a clinical trial in people.

The therapy was developed by Dr. Henry Klassen at the University of California, Irvine (UCI). RP is a relatively rare, inherited condition in which the light-sensitive cells at the back of the retina, cells that are essential for vision, slowly and progressively degenerate. Eventually it can result in blindness. There is no cure and no effective long-term treatment.

Dr. Klassen’s team will inject patients with stem cells, known as retinal progenitors, to help replace those cells destroyed by the disease and hopefully to save those not yet damaged.

In a news release about the therapy Dr. Klassen said the main goal of this small Phase I trial will be to make sure this approach is safe:

“This milestone is a very important one for our project. It signals a turning point, marking the beginning of the clinical phase of development, and we are all very excited about this project.”

Jonathan Thomas, the Chair of our Board, says that CIRM has invested almost $20 million to help support this work through early stage research and now, into the clinic.

“One of the goals of the agency is to provide the support that promising therapies need to progress and ultimately to get into clinical trials in patients. RP affects about 1.5 million people worldwide and is the leading cause of inherited blindness in the developed world. Having an effective treatment for it would transform people’s lives in extraordinary ways.”

Dr. Klassen says without that support it is doubtful that this work would have progressed as quickly as it has. And the support doesn’t just involve money:

“CIRM has played a critical and essential role in this project. While the funding is extremely important, CIRM also tutors and guides its grantees in the many aspects of translational development at every step of the way, and this accelerates during the later pre-clinical phase where much is at stake.”

This is now the 12th project that we are funding that has been approved by the FDA for clinical trials. It’s cause for optimism, but cautious optimism. These are small scale, early phase trials that in many cases are the first time these therapies have been tested in people. They look promising in the lab. Now it’s time to see if they are equally promising in people.

Considering we didn’t really start funding research until 2007 we have come a long way in a short time. Clearly we still have a long way to go. But the news that Dr. Klassen’s work has been given the go-ahead to take the next, big step, is a hopeful sign for Rosalinda and others with RP that we are at least heading in the right direction.

One of our recent Spotlight on Disease videos features Dr. Klassen and Rosalinda Barrero talking about RP.

This work will be one of the clinical trials being tested in our new Alpha Stem Cell Clinic Network. You can read more about that network here.

Using stem cells to mend a broken heart and winning $6,000 to boot

It’s no secret that the members of the CIRM blog team are all big fans of scientists who are good public communicators. We feel that the more scientists talk about their research, the better the public will understand the importance of science and it’s ability to help them or someone they love.

Grad Slam winner, Ashley Fong from UC Irvine

Grad Slam winner, Ashley Fong from UC Irvine

So on Monday when University of California, Irvine researcher Ashley Fong won the $6,000 top prize in the Grad Slam competition for the terrific explanation of her work in using stem cells to treat heart disease, it was doubly gratifying. You see, not only is Ashley a great communicator, but she’s also someone we have helped support in her career.

The Grad Slam is an “elevator pitch” competition sponsored by the University of California Office of the President. Ten graduate students from across the UC system were given three minutes to explain their work to a live audience, using everyday language and avoiding jargon or technical lingo.

All the students were good. Ashley was great. Want proof? Here you go (Ashley comes on at 39.20 into the video.)

She says she discovered her passion for stem cell research thanks to a CIRM-funded summer undergraduate internship. Now she is working in the lab of Chris Hughes at UCI.

In a UCI News story about the competition Frances Leslie, dean of the Graduate Division who hosted the campus-level competition in April, said:

“It’s important for graduate students to explain their research to the general public in ways that are easy to understand. And it’s also critical for the taxpayers of California to see the benefits of their support of graduate education.”

We couldn’t have put it any better.

Charting a new, faster way to fund science and help patients

Change is never easy. In fact, sometimes it can be downright hard. But change is also essential if you want to grow, to get faster and better.

When we launched CIRM 2.0 we set out to produce a better, faster, more effective and efficient way to deliver stem cell therapies to patients with unmet medical needs. Yesterday we got a chance to see how those changes are starting to play out. And it was very encouraging.

Our Grants Working Group (GWG – we love our acronyms at CIRM. See!) is the independent panel of experts that we bring in to review all the applications for agency funding. They come from all over the US, except California, and Monday was the first chance they got to meet in person and vote on our new 2.0 applications.

The day began with a really in-depth look at how 2.0 works and how it differs quite dramatically from the old system. One of the things that always impresses me about the GWG is the extraordinary quality of the questions they ask and the level of detail they want to help them make the best possible decisions. While we would never divulge any applicant’s confidential or proprietary information, we were able to hold much of the meeting in open session – furthering our commitment to transparency.

I think Sen. Art Torres, the Vice Chair and a Patient Advocate member of our governing Board, summed it up best in a note that he sent to the CIRM Team following the meeting:

“Yesterday was a historic day for CIRM.  It was one of the best meetings I have attended and gave me renewed confidence in speaking to the public of how we continue to be responsible stewards of the taxpayers’ dollars while at the same time keeping patients as our number one priority.

I cannot speak for all the patient advocates but I think they were all impressed with the candor and meaningful dialogue that took place.

It also gave the GWG members time to bond in a very welcoming setting to express their ideas and their commitments.  I do not recall ever having a session with GWG members where they shared their personal views other than their reviews of a proposed grant.  It was revealing about how we can work more closely together with our common bonds.”

The results of the review of the first two applications under CIRM 2.0 will go to the Board for a vote on May 21, but the more important outcome will be the long-term benefit to the way we work. The in-person meeting helped the members of the GWG really understand how the changes to the way they work will speed up our ability to fund the most promising science.

This is all new, so it’s likely we’ll hit some bumps along the way. And as we roll out our new versions of 2.0 that cover funding Discovery (or basic) and Translational research later this year we’ll probably have more adjustments to make. You can’t change this much this fast and not run into problems.

But as the meeting yesterday showed so clearly, with the right team behind you even the biggest changes can be taken in stride.

Pioneering treatments: planning first-in-human stem cell clinical trials

Sometimes the reason for the most complex of projects can be boiled down to the most simple of phrases.

Dr. John Adams, Dr. Catriona Jamieson & Dr. John Zaia at the Alpha Stem Cell Clinic network meeting

(left to right) Dr. John Adams, Dr. Catriona Jamieson & Dr. John Zaia at the Alpha Stem Cell Clinic network meeting

At a meeting last week to help plan for our Alpha Stem Cell Clinic network there were lots of great presentations and discussions about the role of the network, how to structure it, what its goals would be. But in the end it was all beautifully, and succinctly, summed up by Dr. Catriona Jamieson who said: “This is great for humanity and this is why we have to do it.”

Dr. Jamieson is heading the University of California, San Diego (UCSD) part of the network. Other partners in this program are City of Hope, UC Los Angeles (UCLA) and UC Irvine (UCI). The goal is to create a network of stem cell-focused clinics that will attract and conduct high quality clinical trials. The stem cell agency is investing $24 million to help create that network.

Why do we need this? Well, stem cells are a whole new way of treating disease, one that requires new skills and expertise, and a new way of working with patients so they understand exactly what is happening.

Many of these clinical trials will be the first time these therapies have been tested in people so Shirley Johnson, RN, the Chief Nursing Officer overseeing the City of Hope program, says you need to have specially trained staff involved.

“We really look to our research patients as being our heroes and particularly our patients that are participating in those first-in-human studies. So having nurses who understand the study protocols, who understand the potential side effects that might be occurring, the symptoms that might be manifested are critical points as we think about first-in-human studies and those things that might occur, and then how best to respond to them.”

One of the reasons we are creating the Alpha Stem Cell Clinic network is because it fits in perfectly with our mission of accelerating the development of stem cell therapies to help patients with unmet medical needs. The network will not just focus on planning and carrying out clinical trials, but will also focus on how those treatments will be paid for, so that life-changing therapies won’t cost patients an arm and a leg.

Dr. John Adams, who heads the UCLA-UCI program, says there will be many obstacles to overcome, but that this is an exciting time:

“The idea behind the Alpha Clinics is to provide an infrastructure to accelerate and make it dead easy for the researchers doing this work to get their work done efficiently, effectively and faster, so that it’s more beneficial for the patients who are undergoing the treatment. And certainly it will allow us to collect more data, and better data, during the course of these clinical trials.”

The data gathered in these trials, and the lessons learned in doing them, will then be shared with others in the network to help create a system of best practices, to make it easier to carry out future clinical trials.

As Dr. John Zaia, who heads the program at City of Hope says: “This is really the beginning of a new era, the era of regenerative medicine.”

You can read more about our Alpha Stem Cell Clinic network, and find links to the individual programs here.

A new approach to killing blood cancer

It’s not often that you get a therapy named after you, particularly one that has so much promise for helping to save lives. So when researchers at the University of California, San Diego Moores Cancer Center named the treatment Cirmtuzumab after us it’s understandable we should feel just a little pride. After all, we provided the funding and support needed to develop it. Now Cirmtuzumab is being used in a clinical trial to treat chronic lymphocytic leukemia (CLL) a deadly blood cancer. Cirmtuzumab is a monoclonal antibody drug and is designed to attach itself to a protein called ROR1 that CLL cells need to survive and spread. The idea is that if you block ROR1, you can block the growth of the cancer. Ivanhoe Broadcasting, a company that syndicates medical stories to TV stations around the US, recently featured this trial. You can see that report here. kipps2013Dr. Thomas Kipps, who is heading the trial, told Ivanhoe that CLL is an important disease to target: “This is the most common adult leukemia in western societies. We have early data now to suggest this antibody may be effective at preventing the relapse and metastasis of cancer.” It’s always encouraging when a promising therapy moves out of the lab and into clinical trials. Reaching this point is the culmination of years, sometimes decades, of hard work and while this is an important milestone, it’s just the first step in a long journey. But now we get to put it to the test and see if it will work in people. If it does, then that will be something to be truly proud of.

Why TED Talks are ChildX’s Play

When the TED (Technology, Entertainment, Design) talks began in 1984 they were intended to be a one-off event. So much for that idea! Today they are a global event, with TED-sponsored conferences held everywhere from Scotland to Tanzania and India. They have also spawned a mini-industry of copycat events. Well, their slogan is “Ideas Worth Spreading” so in a way they only have themselves to blame for having such a great idea.

Dr. Maria Grazia Roncarolo

Dr. Maria Grazia Roncarolo

The latest place for that idea to take root is Stanford, which is holding a TED-style event focused on critical issues facing child and maternal health. The event – April 2nd and 3rd at Stanford – is called ChildX where x = medicine + technology + innovative treatment + wellbeing. ChildX will bring together some of the leading experts in the field for a series of thoughtful, powerful presentations on the biggest problems facing child and maternal health, and the most exciting research aimed at resolving those problems. One of the main tracks during the two-day event is a section on stem cell and gene therapy. It will raise a number of key questions including:

  • What advances have occurred to enable these therapies to move from science fiction less than a decade ago to the promise of next generation transformative therapeutics?
  • In coming years, how will these therapies allow children with presently incurable diseases to become children living free of disease and reaching their maximum potential?

The moderator for that discussion is Dr. Maria Grazia Roncarolo, and you can hear her talking about the most recent advances in the clinical use of stem cell and gene therapies on this podcast. Anytime you get a chance to hear some of the most compelling speakers in their field talk about exciting innovations that could shape the future, it’s worth taking the time to listen.