UC Researcher on Stem Cells and California's Stem Cell Agency

The California stem cell agency recently highlighted a brief look at the field with a Q&A that ranged from the impact of the agency itself to dealing with questions about "miraculous" stem cell "cures."

The item appeared on the agency's blog and originated at UC Davis, which is among the top five recipients of funds from the agency, known formally as the California Institute for Regenerative Medicine (CIRM).

The school has received $143 million, making it fifth on the list of recipients in terms of dollars.

The Q&A involved Jan Nolta, head of the stem cell program at UC Davis. Some excerpts from what Nolta had to say:

Jan Nolta, UC Davis photo

"Perhaps the most promising and exciting research right now comes from combining blood-forming stem cells with gene therapy. 

"Along with treating the famous bubble baby disease, where I had started my career, this approach looks very promising for sickle cell anemia. We’re hoping to use it to treat several different inherited metabolic diseases.... 

"The beauty of this therapy is that it can work for the lifetime of a patient. All of the blood cells circulating in a person’s system would be repaired. It’s the number one stem cell cure happening right now. Plus, it’s a therapy that won’t be rejected. These are a patient’s own stem cells. It is just one type of stem cell, and the first that’s being commercialized to change cells throughout the body."

About the five Alpha stem cell clinics initiated by CIRM, Nolta said,

"These are clinics where the patients can go for high-quality clinical stem cell trials approved by the FDA [U.S. Food and Drug Administration]. They don’t need to go to 'unapproved clinics'a and spend a lot of money. And they actually shouldn’t."

A Chance to Peek Inside a $50 Million California Stem Cell Program

Video from 2017 Alpha Clinic symposium

One of the better stem cell, show-and-tell conferences is coming up this spring in San Francisco, plus it is free and open to the public.

The day-long session will provide a peek inside one of the signature efforts of California's 14-year-old, $3 billion stem cell research program, which is edging closer to ever more critical financial times. 

The meeting April 18 is the fourth annual Alpha Clinic symposium. The Alpha Clinic Network was created in 2015 by the California Institute for Regenerative Medicine(CIRM), as the stem cell agency is formally known. 

CIRM has pumped $50 million into the network, which is aimed at delivering clinical trials to patients, creating strategic relationships between science and industry and leveraging statewide resources. Sites for the network are located at the City of Hope and at UC campuses in San Francisco, Davis/Sacramento, San Diego, UCLA and UC Irvine.

For those interested in California public policy issues dealing with health, medical mattters and research, the symposium will offer an up-close opportunity to check out the impact of the state stem cell agency. 

The session promises updates on stem cell research and clinical trials on afflictions ranging from sickle cell disease to cancer along with a look at gene editing. Scientists and patient advocates will be telling their stories and detailing the research.

CIRM is scheduled to run out of cash for new awards this year. It is attempting to raise privately $220 million to bridge a financial gap before hoped-for voter approval of $5 billion more in funding in November 2020.

Geoff Lomax, CIRM's senior officer for strategic infrastructure, told the California Stem Cell Report via email last week:

"It’s an exciting time in medicine as we have the tools to literally mend cells at the DNA level. The annual symposium is an opportunity to hear from the pioneers who developed these tool, the Alpha Clinic doctors and nurses that use them and the patients that have benefited from them."

Here are links to more information about the Alpha Clinic Network: Agenda for the symposium. CIRM's Alpha Clinic page, a CIRM blog item on the April meeting. 

The session this spring is financed with $60,000 from the stem cell agency.

California's $50 Million Alpha Network: Managing the Complexity of Stem Cell Clinical Trials

Clinical Leader, an online publication dealing with clinical trials, yesterday carried a piece exploring the $50 million Alpha Clinic program initiated by the California stem cell agency.

Written by Geoff Lomax, a senior officer at the agency for its strategic initiatives, the article discussed the complexity of stem cell clinical trials and the use of a network of high-powered medical centers to support the novel research and treatment, particularly involving the FDA's programs to speed use of some therapies. 

Lomax's concluding statement in the article said,

"(R)egenerative medicine therapies are treating and curing debilitating and deadly diseases. The FDA’s RMAT (regenerative medicine advanced therapy) and breakthrough designations have created a streamlined environment for product sponsors. To effectively leverage this regulatory policy environment, sponsors must conduct high-quality clinical trials that are often operationally complex.

"Clinical trial networks, capable of managing the array of regenerative medicine technologies, are well suited to manage this complexity. The CIRM Alpha Clinic network is a current highly functioning proof of the concept. Patients with unmet medical need and product sponsors will benefit from the replication of this model nationally and internationally."

The agency, formally known as the California Institute for Regenerative Medicine or CIRM, initiated the Alpha network in 2015. It has since enlarged the effort with a total of $50 million and locations at UC San Francisco, UC Davis, UCLA, UC Irvine, City of Hope and UC San Diego. 

The Clinical Leader piece said, 

"Recognizing this operational complexity and limitations in clinical experience, the California Institute for Regenerative Medicine (CIRM) pioneered the development of infrastructure to support regenerative medicine clinical trials. Launched in 2015, the CIRM Alpha Clinics are a network of six California medical centers. The clinics conduct FDA-authorized and IRB approved clinical trials. The aim of the network is to achieve greater and more efficient results than the member organizations could if they acted independently. Each of the Alpha Clinics has formed teams with specialized knowledge and experience with regenerative medicine clinical research involving human cell and tissue products. These teams work across their respective centers. As of September 1, 2018, the network is supporting 49 clinical trials — and has supported 60 clinical trials since 2015 — across a range of indications."

Lomax continued,

"This network model of conducting therapeutically diverse clinical trials lies in contrast to the traditional disease-based clinical trial networks that tend to be located in specific clinical units – oncology, cardiology, neurology, etc. The Alpha Clinic teams are horizontally integrated across the centers, so they can support the diverse range of indications where regenerative medicine therapies are currently being evaluated. This technology-based approach facilitates the conduct of clinical trials, particularly in clinical units that may have limited experience with cell and gene therapy products."

California's Alpha Stem Cell Clinics: A 21-Video Overview of the $40 Million Effort

The great mysteries and not-so-great mysteries of the stem cells and their likely applications are the subject of a host of videos drawn from a day-long meeting this month at the City of Hope in California.

The occasion for presentation of the clips on You Tube was a symposium on California's Alpha Clinic network, which is scheduled to expand from three to five sites this year. That will boost the state investment in the network to $40 million.

The March 23 session included discussion of the results of some of the research at the sites -- City of Hope, UC San Diego and UCLA/UC Irvine. Patients spoke as well, and there were discussions of the economic barriers involving commercialization of stem cell therapies.

Of particular interest was a nine-minute look at "stem cell therapy value and reimbursement considerations" by Jennifer Malin of United Healthcare.  That video is at the top of this item.

The Alpha network was initiated by California's $3 billion stem cell agency. Geoff Lomax, the agency's senior officer for strategic initiatives, presented an overview of the program. Below is a video of Bob Klein, the agency's former chairman, in which he indicates he will be backing a $5 billion bond measure to keep the agency going beyond 2020, when its funds run out.

Twenty-one videos are available. Here is a link to the agenda, which is useful as a guide to pick videos that are more likely to be relevant to a viewer's particular interests.

Slim Coverage of California's Ambitious Alpha Stem Cell Clinic Network

CIRM chart showing jump in clinical trials at institutions
 currently in the Alpha Clinic Network

Last week California's soon-to-be $40 million Alpha stem cell clinic network drew attention from within the stem cell community but little notice in the media.

A symposium last Thursday at the City of Hope on the effort covered aspects of the effort ranging from its results to what patients had to say. As of this morning, only one story had surfaced.

Claudia Palma of the Pasadena Star-News wrote a piece that sketched out something of an overview, including quotes from John Zaia, the principal investigator for the Alpha clinic at the City of Hope. Other clinics are in place at UC San Diego and UCLA/UC Irvine.

The $3 billion, California stem cell agency initiated the program in 2014 and plans to add two more sites this year.

Capitol Weekly, an online news service focusing on state government, picked up the article from the symposium by the California Stem Cell Report on an effort to keep the agency going after it runs out of money in 2020.

Stem cell agency officials also appeared at the conference, including Geoff Lomax, senior officer for strategic initiatives, who laid out the Alpha Clinic program. His presentation highlighted the boost in number of stem cell trials at the three institutions plus

CIRM graphic on Alpha trials and range of afflictions

California Popping for $40 Million for its Alpha Clinic Stem Cell Centers

CIRM video

California this year expects to add two new Alpha stem cell clinics to the three already in Southern California, boosting its investment in the effort to as much as $40 million.

The move came last Thursday when directors of the state's $3 billion stem cell agency approved seeking additional Alpha Clinic applications this spring. The purpose of the clinics is to accelerate development of stem cell therapies, a key goal of Proposition 71, the ballot measure that created the California Institute for Regenerative Medicine or CIRM as the Oakland-based program is known.

Expansion of the program could also mean that an Alpha site may be located somewhere in Northern California by the end of this year. One of the objectives of the latest proposal is to broaden the "geographic reach" of the Alpha network.

According to CIRM, the existing Alpha clinics already have 33 clinical trials underway for 12 different afflictions. Randy Mills, president of the agency, said in an interview Friday with the California Stem Cell Report that the clinics doubled the number of stem cell trials that they had prior to launching their CIRM Alpha programs. Many of those trials do not require agency funding, which allows the cash to be used elsewhere.

Maria Millan, CIRM's vice president for therapeutics, told CIRM directors last week,

"Once we built it, they did come."

The latest expansion is aimed at increasing capacity and access to stem cell trials, training physician/scientists in clinical trials and bringing additional assets to California's Alpha clinic network, which is also positioned to help establish the state as the global leader in stem cell treatment.

The request for applications, with a deadline of May 15, will also require that the clinics -- whether non-profit or for-profit -- create a "sustainability plan," which will keep them operating after the CIRM funding terminates in four years. The agency itself expects to run out of cash for any new awards even sooner -- June 2020.

CIRM is offering to provide two winners in the Alpha round $8 million each over a four-year period with milestones required to keep the cash flowing.

During Friday's interview, Mills said that applicants from Northern California will need to make a case for the "added value" that they will bring to their proposals and demonstrate that their populations are underserved. Additional applications are likely to come in from Southern California, which has the bulk of the state's population and patients.

The current Alpha Clinics are located at the City of Hope in Duarte, which is in the Los Angeles area, UC San Diego and UCLA/UC Irvine.

A symposium on Alpha Clinics is scheduled for March 23 at the City of Hope. Advance registration is requested.  

City of Hope video

California to Hand Out $32 Million for Stem Cell Research Next Week

The California stem cell agency next week is expected to award as much as $32 million for late stage research and clinical trials involving therapies for arthritis of the knee, type 1 diabetes, an immunodeficiency affliction and ALS. 

Also on tap for the Feb. 23 governing board meeting are concept proposals for expansion of the Alpha Clinic program along with unspecified changes in the $3 billion agency's discovery, translation and clinical plans. 

Four awards are already approved by the agency's reviewers and are scheduled for routine ratification by the board. Their review summaries can be found on the agenda. The reviewers also rejected one proposal for research involving Parkinson's disease. That summary can also be found on the agenda.

More details on the concept plans are expected to be posted soon. The meeting will take place in Oakland with public teleconference locations in in San Diego, Los Angeles and two in La Jolla. Addresses can be found on the agenda. 

$16 Million Expansion of Alpha Stem Cell Clinics Planned for California

California's stem cell agency plans to expand its Alpha Clinic network this year with two more locations, including probably the first in Northern California, and financing the effort with $16 million. 

The proposal comes before the agency's Science Subcommittee one week from today (Jan. 25) and could be of considerable interest to enterprises, both public and private, that are ready to move quickly. The $3 billion agency has set a deadline of May 15 for applications. 

The Alpha Clinic program is aimed at being sort of a one-stop center for clinical trials and stem cell research. Currently sites are all located in Southern California at UC San Diego, the City of Hope in the Los Angeles area, UCLA and UC Irvine. 

The agency, known formally as the California Institute for Regenerative Medicine (CIRM), said in its proposal, 

"Twenty-nine clinical trials are being conducted at these sites and hundreds of patients have been enrolled. These trials emanate from CIRM’s funding pipeline as well as non-CIRM funded investigator and industry-sponsored projects."

One of the goals of the expansion is to enhance the value of the network. The agency said, 

“Proposed sites could enhance the value by, for example, broadening the network’s geographic reach, providing expertise in new disease areas, providing new/unique technical capability, or other elements that accelerate/support stem cell clinical trials.”

The session next week will provide an opportunity for potential applicants to ask questions and make suggestions. The proposal will also go to the governing board of the agency, but most of the work by board members goes on at the committee level.

Applicants may also be interested in a CIRM symposium on Alpha Clinics scheduled for March 23 at the City of Hope.

Next week's committee meeting will be based at the agency's Oakland headquarters with five telephonic locations, all public, two in Los Angeles, and one each in San Diego, Irvine and La Jolla, where the public can participate. The meeting will also be audiocast with listen-only capabilities. Details are on the agenda.

Also on the agenda are unspecified changes in three other types of CIRM award rounds: Discovery, Translation and Clinical. The agency has not yet posted material spelling out what is to be considered.

California's $30 Million Stem Cell 'Pitching Machine'

LOS ANGELES -- Above is a look at the California's stem agency's plan to support efforts to advance research into clinical trials. Two, $15 million centers are planned. They would perform the "back room" work that does not have appeal to research scientists.

California's Alpha Stem Cell Clinics Garner Little News Coverage

The California stem cell agency’s $34 million Alpha clinic venture last week received minimal attention from the mainstream media.

The effort was also was subordinated by the agency itself, which issued a press release that focused heavily instead on the plan by its new president, Randy Mills, to improve operations at the agency.

News stories, however, led with the action on the Alpha clinics. Articles appeared by Bradley Fikes in the San Diego U-T, Rebecca Kheel in the Orange County Register and in The Sacramento Bee by yours truly. John Schreiber of City News Service in Los Angeles also wrote a brief article that was picked up by smaller outlets.

The occasion was approval of the first stage of the Alpha clinic plan, which was originally budgeted for $70 million by former agency president Alan Trounson and the agency board.

Last Thursday, the agency’s board handed out three awards of $8 million each, trimming the applicants’ proposals by as much as 26 percent.  Next year, the agency is expected to add a $10 million information/data center to the Alpha effort. The center was cut from $15 million earlier this year.

The winners last week were the City of Hope, Duarte, Ca.; UC San Diego and UCLA/UC Irvine. The latter two issued press releases quickly (see here and here), but the City of Hope has still not issued one.

The press releases provided a few more details about the research, including the names of the principal investigators. At UC San Diego, it is Catriona Jamieson, deputy director of the Sanford Stem Cell Clinical Center. For the UCLA/Irvine effort, it is John Adams, a member of the UCLA Broad Stem Cell Research Center and professor in the department of orthopaedic surgery. Donald Kohn and Antoni Ribas are directing the two clinical trials. Normally the stem cell agency identifies the principal investigators in a press release following board action but did not do so in this case.

(An earlier version of this incorrectly said Kohn and Aribas were the principal investigators for UCLA-Irvine.)

California's Alpha Stem Cell Clinic Plan Hits Budget Buzz Saw

The $3 billion California stem cell agency today put the squeeze on applicants in its ambitious Alpha stem cell clinic round, which is aimed at helping to make the Golden State a global leader in stem cell treatment and research.

The action came as one rejected applicant, UC Davis, publicly appealed to the agency’s governing board to overturn tomorrow a negative decision by the agency’s out-of-state reviewers.  Cedar-Sinai in Los Angeles also filed a letter aimed at beefing up consideration of its application, which wound up on the reviewers’ funding fence.

                                                                                                                                                         

A proposal by Randy Mills, the agency’s new president, however, contained the most surprising news – a plan to cut millions from the budgets of the expected winning applicants – City of Hope (application AC1-07659), UC San Diego (AC1-07764) and UCLA (AC1-07675).

The cuts were specified in a slide presentation  posted  yesterday or today for the board meeting in Los Angeles tomorrow. The presentation recommended approval of the three applications but with revised budgets to hit a funding cap of $8 million each. The reviewers had recommended approval of the three with budgets ranging from about $11 million to $11.7 million. 

The presentation and another document based on the closed-door review indicated that reviewers were concerned about duplicative clinical trial costs and expenses associated with a proposed $10 million information center, which was trimmed earlier this year from $15 million. The request for applications to create the center is being rewritten to sharpen its focus.­­­

The other document from the review represented the first time that such a commentary has been prepared and released publicly. It was requested by an unidentified agency board member who was present at the review session.  (When queried, the agency later identified the member as Os Steward, director of the Reeve-Irvine Research Center at UC Irvine.)

 The unusual document said, among other things,

“Some reviewers had questions regarding the wording of the RFA and the potential for duplication of costs. Specifically, there was confusion over the portion of the RFA that listed ‘Clinical Trial Costs’ as specifically being outside the scope of the RFA, while simultaneously permitting  a funded Alpha Clinic to ‘defray some costs, such as clinical operations.’”

As originally proposed, the Alpha plan would have hit $70 million with up to five clinics, although there was no requirement to fund that many. It is now down to something around $40 million if four applications are approved tomorrow at $8 million each, and the information center moves forward with $10 million.

The four-page letter from the Cedars-Sinai Medical Center in Los Angeles to the directors of the stem cell agency was signed by Timothy Henry, director of the division of cardiology.  Reviewers gave the $11 million application (AC1-07650) a scientific score of 68 and said,

“Given the large expansion into regenerative medicine that the institution has undertaken, many of the activities described as elements of the (Alpha clinic) have already been initiated or will soon be put in place. Some reviewers questioned whether the additional resources provided by (Alpha) funding would substantially supplement ongoing activities and if the (Alpha clinic) would add significant value." 

Henry’s letter did not appear to break new ground but emphasized the strengths of Cedars-Sinai, declaring that one of the clinical trials proposed is “the furthest advanced of any CIRM-funded trials.”

The score for the UC Davis’ $10.8 million application (AC1-07637) was not released by the agency.  Reviewers said,

 “While some reviewers felt that the large number of trials ongoing or planned would clearly benefit from additional resources, others questioned the added value of establishing a (an Alpha clinic) at this site and did not think the application clearly conveyed how CIRM funds would be used to leverage and enhance the already ongoing activities.”

The three-page Davis appeal letter was signed by Ted Wun,  chief of hematology oncology, Jan Nolta, director of the UC Davis stem cell program, and Frederick Meyers, vice dean of the UC Davis School of Medicine.

The letter said that since the review of its application, it has received a favorable FDA judgment on a proposed clinical trial for HIV that would begin in 2015.  In an attempt to deal with concerns about personnel, Davis said the Alpha clinic would pull over the most experienced researchers with their old positions being “backfilled.”

The letter also noted Davis’ location in Northern California. All of the top-ranked applications are situated in Southern California, presenting a scientific-geopolitical issue for the statewide stem cell agency.

(The stem cell agency does not release the names of winning applicants prior to board action. However, they were derived by the California Stem Cell Report from a variety of sources.  All of the reviews can be found on this document.) 

No Appeals Filed Yet in California's $44 Million Alpha Stem Cell Clinic Round

None of the rejected California universities seeking multimillion dollar grants to join the Golden State’s new, ambitious network of Alpha Stem Cell Clinics has yet filed an appeal of the decisions, the state stem cell agency said today.

That word comes from Don Gibbons, a spokesman for the $3 billion enterprise. In response to a query from the California Stem Cell Report, he said, however, the deadline for appeals is Friday.

If appeals are filed as expected, they will handled behind closed doors by the agency’s staff. Under state law, the applicants can also appear publicly before the agency’s governing board on Oct. 23 in Los Angeles to make their case. The board, however, has not responded favorably to most such pitches in the last year or so.

The Oct. 23 meeting will be the first public vetting of the proposals, which are outlined briefly in review summaries. The summaries were prepared by the agency's staff following closed-door meetings in which out-of-state scientific reviewers voted the applications up or down. The board almost never rejects a positive decision by its reviewers. Occasionally, it will approve an application that is rejected by reviewers.

Three applications survived the private review and total about $33.6 million. A fourth is on the fence for $11 million more. The agency refuses most of the time to disclose the names of applicants. But based on the review summaries and other information, the City of Hope, UC San Diego and UCLA appear to be the top-ranked applications. 

California to Spend Up to $44 Million for Ambitious Alpha Stem Cell Clinic Plan

California late next week is expected to plunk down as much as $44 million to help make the Golden State the global leader in stem cell research as well as a go-to location worldwide for patient stem cell therapies.

The ambitious proposal comes from the state's $3 billion stem cell agency which aims to create high-powered Alpha Stem Cell Clinics at major universities around the state. The clinics would be one-stop centers for stem cell treatment and would be designed to attract patients from throughout the world.

Afflictions under attack include cancer and heart disease along with diabetes and spinal cord injury.

Just who will get the cash will be determined on Oct. 23 when directors of the agency will meet in Los Angeles to consider seven proposals. The directors will be working from summaries of the closed-door review and subsequent decisions on the applications by the agency’s blue-ribbon panel of out-of-state reviewers. 

The reviewers approved three proposals for a total of $33.6 million. A fourth, $11 million application received partial support but fell short of a flat recommendation for funding, which agency directors almost never reject. However, the board could decide to back the proposal despite reviewers' concerns. 

All of the applications come from the cream of California universities. The agency withholds the identities of grant applicants in nearly all cases until after the board acts. However, proposals from the City of Hope and UC San Diego appear to be ranked No. 1 and No. 2. UCLA is ranked No. 3, based on the review summaries and other information.

Other likely applicants include USC,  UC San Francisco and Children’s Hospital Oakland,  UC Davis, Stanford and UC Irvine. Some of the proposals brought together two or three institutions. 

All of the institutions have representatives on the 29-member governing board of the California Institute of Regenerative Medicine(CIRM), as the agency is formally known. They will not be allowed to vote on or discuss applications involving their institutions or businesses.

Viacyte, Inc., of San Diego, also appears to be a beneficiary because of its involvement in a trial with UC San Diego, one of the three top applicants (see the review summary for application 7764.) Viacyte has already received $55 million from the agency.

All of the clinical trials proposed or underway are early stage efforts. With early trials, the general odds of a specific therapy becoming available for widespread use are slim and could take a decade or more. 

The three apparent winners are all located in Southern California, leaving Northern California unrepresented, which poses a ticklish scientific-political problem. If the 4th-ranked application is located in Northern California, that fact could well push it into approval.

However, the review summary of the application said,

"The PD and institution have ties to one of the lead clinical trials, which could result in the appearance of a conflict of interest. Reviewers commented that policies should be in place to ensure that the relationships are clearly defined and separated."

The candidates rejected outright by reviewers may well appeal the decisions. The California Stem Cell Report has queried the agency concerning appeals, but the agency has moved much of the appeals process behind closed doors to be handled by its staff. Previously appeals often came directly to the board in public. However, applicants still have the right to appear before the board on any matter.  

Also undisclosed is the full amount of matching funds and other commitments offered by the competing applicants, which appear to be substantial. One applicant (application 7650) mentioned $10 million in its review summary.  Another applicant, which appears to be UC San Diego, touted a single, large private donor. Multibillionaire Denny Sanford has funneled $100 million into stem cell research through a linkage with the San Diego university.

The Alpha Clinic plan is the brainchild of former stem cell agency president, Alan Trounson, who is not expected to attend next week’s meeting. Trounson earlier this year resigned to return to Australia. Seven days after he left the agency, he accepted an appointment to the board of StemCells, Inc., which has received $19 million from CIRM. The agency was shocked by the move and suffered a spate of bad publicity as a result.

Trounson first broached the Alpha concept in 2011.  And in 2013, he told the Los Angeles Times, 

“It will make California a go-to place for stem cell therapies. I want to make sure it's part of our medical fabric."

An article in the journal Nature Medicine said the proposal would create the first-ever “clinical trials network focused around a broad therapeutic platform.”

To dig into the applications and scores, see this document. All of the review summaries are jumbled into the document, but you can scroll through or use a search tool to find specifics. 

California's Far-Reaching Alpha Stem Cell Clinic Plan Likely to Take a Hit

The new president of the California stem cell agency today recommended cutting $5 million from the agency’s ambitious Alpha stem cell clinic plan, declaring that the proposal’s $70 million cost is “not clearly justified.”

If the agency’s board goes along with the recommendation at Thursday’s meeting, it will be the first time the $3 billion agency has so radically and retroactively reduced a proposal in its nearly 10-year history.

Randy Mills

In a memo posted early today on the agency’s Web site, Randy Mills, who joined the agency in May, said,  

“While all of the aims of the concept plan are individually laudable, it is my firm belief that the proposal as written is too broad and overly complex to be successful. In a word, it lacks focus. As a result of its overly wide-ranging scope, I also believe that there is a real possibility of incurring significant duplicative costs. Following a thorough review and conversations with senior members of the CIRM team, it is my opinion that the $70 million price tag is not clearly justified in terms of the benefits it will deliver to the people of California.”

The Alpha stem cell clinic program was heavily promoted by the former president of the stem cell agency, Alan Trounson. It is aimed at making the Golden State the world’s “go-to” location for stem cell therapies.

Mills said, however, that a $15 million component creating a data/information center should be stripped from the plan and whittled down to $10 million.

He said the center’s efforts to combine aspects of clinical operations, data sharing, education/marketing and lobbying for insurance coverage of stem cell therapies would create an “unwieldy program.” Instead, he said the Alpha effort should focus on early stage clinical operations  – “efforts directly related to high quality stem cell clinical trials.”

Mills’ proposal comes late in the game for the Alpha awards. Applicants have already submitted their proposals. The review of the applications was originally scheduled to occur last month. However, in one of his first public acts, Mills postponed the review, which is now scheduled for September.  The reason for the delay, the agency said in June, was the difficulty in finding reviewers.

However, the information center component is contained in a separate RFA and could be easily discarded. The only damage would be the time that the five applicants spent on preparing their applications, which is no small task, and the work that the CIRM staff has done so far.

Mills told the board in the memo,

“I realize that making this recommendation after the submission of applications for the CIMC (the data center) is not optimal. However, given the magnitude of the spending proposed, not sharing this critical assessment with the board would be a greater disservice. I believe that these recommendations are not only fiscally responsible, but more importantly, give the program the greatest chance of success to accomplish our mission of getting stem cell treatments to patients in need.”

Mills is also recommending alterations in the clinical portion of the Alpha plan, which involves eight separate applications, all of which are likely to have come from institutions with representation on the stem cell board.  Mills said he wanted  “a staged approach to funding, where we evaluate with proper metrics, the effectiveness of the program in a limited number of sites before expanding.”

Mills’ Alpha memo does not appear to envision modifying the RFA, so presumably the staged funding would be dealt with in negotiations following board action on the applications, which will probably occur later this year.  Up to five awards are scheduled to be made.

Mills’ Alpha cuts are virtually certain to be approved by the board. Rejection of his recommendations would amount to a vote of no-confidence in Mills and would likely result in his resignation. (On Thursday, however, he assured the board he would not quit if it did not go along.)

Even earlier this year, Mills, who has made his career in business, demonstrated his parsimony. Trounson’s proposed operations 2014-15 budget for the agency was submitted in early May at $17.9 million, an increase of 9.5 percent increase over estimated 2013-14 spending. Mills sliced the spending plan to $17.3 million, maintaining it at virtually same level as last year – lower if inflation is factored in.

(An earlier version of this item incorrectly stated that Mills wanted to cut the program by $15 million.)

California Stem Cell Agency to Alter $70 Million Alpha Clinic Proposal

The California stem cell agency is moving to revise a significant component of its $70 million plan to create one-stop Alpha clinics aimed at establishing the Golden State as the leading location worldwide for stem cell therapies.

Details of the changes that will be considered at the July 24 meeting of the agency’s board are not yet available. However, they deal with creation of a $15 million data and information management center that would be involved in clinical trial support, outreach and education and “development of healthcare economic resources.” The last area would involve efforts to convince insurance companies and the government to pay for what are likely to be very expensive treatments. 

The Alpha clinic applications were scheduled to be reviewed last month behind closed doors by the agency’s out-of-state reviewers. However, the June review was postponed shortly after Randy Mills became the new president of the agency. The agency said it was having difficulty getting qualified reviewers.  The review is now set for mid-September.

The Alpha clinic proposal has been championed for several years by the agency’s former president, Alan Trounson, who is now involved in a conflict-of-interest flap. Last week, he was appointed to the board of StemCells, Inc., of Newark, Ca., which is the recipient of a $19.4 million award from CIRM. The agency has launched a review of all activities involving the publicly traded firm and banned CIRM employees from speaking to Trounson about StemCells, Inc., matters.  

Mills began his presidential duties May 15 at which time Trounson was designated as a senior scientific advisor. Early in May, Kevin McCormack, CIRM spokesman, said that Trounson would remain with the agency until June 30. McCormack said that Trounson would  “help shepherd through a number of projects and commitments he has made,” which some assumed included the review of the Alpha applications in June.

McCormack did not response to a question on June 6 about whether Trounson would be participating in the review.

Eight, unidentified major institutions are competing for the Alpha clinic awards. Five are specifically shooting for the information management center.  StemCells, Inc., is not expected to be involved because of the terms of the RFA, but Stanford University is quite likely to be among the applicants.

Stanford scientist Irv Weissman, founder of StemCells, Inc., and currently a member of its board and chairman of its scientific advisory board, is head of the Palo Alto school’s Institute of Stem Cell Biology and Regenerative Medicine.

The CIRM board meeting will be held in Millbrae but two teleconference locations, where the public can participate, will be available in Los Angeles  and one in La Jolla. Specific locations can be found on the agenda.

California's Trounson Wants to 'Shame' the 'Malefactors' of Stem Cell Medicine

Alan Trounson at Cornell
Cornell photo

The former president of the California stem cell agency, Alan Trounson, has kept busy since leaving his post last month. Just this week he authored an opinion piece in The Scientist. Earlier this month he was at Cornell decrying the lack of federal funding for research.

In his article in The Scientist, Trounson called for the outing of stem cell clinics that sell untested and expensive treatments to desperate people.  “Malefactors” is what he called them.

He wrote,

 “It is time that a ‘shame file’ of unregistered and unscientific treatment centers is constructed and widely communicated to warn patients of the dangers of these unregulated and inadequately managed therapies being offered internationally.”

Trounson suggested that the Institute of Medicine could host such a file and help protect uninformed patients. But he also said Alliance for Regenerative Medicine, an industry group that is also engaged in lobbying, could do better in helping to expose dubious stem cell clinics.

He said,

“While this organization and its members do not approve of unregistered clinical trials, they ought to be more active in ensuring the scientific integrity of all studies going forward.”

Trounson said that the $70 million Alpha clinic effort that he championed at the California stem cell agency is also aimed at tackling the problem. Grant applications in that program are due to be reviewed this fall. 

Trounson warned that fringe stem cell clinics damage the entire field.

“The activities of these medical tourism centers are a major barrier to the delivery of genuine cell therapeutic clinical trials by bringing the whole field of cell-based therapies into disrepute.”

At Cornell on June 6, Trounson, who is a senior scientific advisor at CIRM until the end of this month, was the keynote speaker for a symposium on stem cells that also featured broadcast journalist Charlie Rose.

The university put out an item on the appearance. Trounson was quoted as saying,

"The [federal] government looks handicapped in this area. You've got a budget situation where you cannot seem to put more money into research — in fact, less money is going into research. We have to convince the people elected to government that this is an incredible revolution and that we need to keep funding the science."

That could be a pitch for the California stem cell agency as well. It is scheduled to run out of money for new grants in less than three years and is currently looking at ways to develop new funding sources.

California's $70 Million Alpha Stem Cell Clinic Competition Ratchets Up

A $70 million race was kicked off last month as the California stem cell agency invited eight institutions to compete to create what it calls Alpha Clinics, enterprises that would attract patients from throughout the world for stem cell therapies.

The agency hopes the plan will lay a foundation for the stem cell industry in California and capitalize on the growing allure of stem cell treatments. CIRM President Alan Trounson, who plans to leave the agency this year, has been pushing the Alpha Clinic plan since 2011.

Beyond the agency's millions, CIRM has told applicants rather delicately that they have an obligation as well. “Show us the money” is the message obliquely contained in the agency's request for applications (RFA) for the Alpha awards.

The issue of matching funds is a tender spot for the agency this week given the flap that arose in the recent $40 million stem cell genomics round. A requirement for contributions was not mentioned in that RFA, leading some unsuccessful applicants to not include any. Stanford won with what it says is $7 million in matching funds.

CIRM's Alpha Clinic RFA does not mention cash, matching or money. But it does say the selection criteria involves in-kind or “other forms of support” and “sustainability,” which usually means a plan for raising cash or showing that cash is in hand. A coupled RFA is a tad more explicit. It mentions criteria involving “financial strength,” leveraging “assets” and “effectiveness in attracting a funding steam” after the award runs out. One or more applicants may think that the best way to show effectiveness in funding is to demonstrate it from the very beginning with a handsome sum.

Eight existing academic centers with hospitals were invited to apply last month to become Alpha Clinics, which will be one of CIRM's signature efforts, given the size of the round and its scope. Up to five awards will be made in that $55 million plan.

In a related RFA, five applicants have been invited to apply for one $15 million award to create a stem cell information and data management center. Not all of the five have been invited to apply in the clinic round. Awards in both categories will be for five years.

Kevin McCormack, senior director for communications at CIRM, said the invitations to compete were culled from 14 letters of intent to apply. The stem cell agency generally declines to disclose the identities of applicants for awards, although it has done so on at least one occasion in the past.

CIRM says its Alpha Clinic plan is aimed at providing “critical operational support for the conduct of clinical trials for investigational stem cell therapies” and to create “centers of excellence” for approved stem cell therapies. Applicants should show that at least two “lead clinical trials” will be conducted at their institutions along with a “committed source of funding” for each trial. CIRM said it would not pay for the trials or construction or renovation of facilities.

In addition to gathering medical data, the $15 million information center will be involved in marketing to potential patients and public communication. The RFA calls for the center to campaign against the “dangers of stem cell tourism,” which is increasingly growing overseas. The information center will also be involved in developing data to convince insurance companies and governments to cover the cost of stem cell therapies, which are predicted to be very expensive.

Because no more than five clinics may be funded, the chances for the eight are good. However, the CIRM governing board is increasingly feeling financially pinched as the agency's funds dwindle. Cash for new grants is expected to run out in the latter part of 2017. The board could back away from the idea of five clinics depending on what grant reviewers say.

Applications are due March 14. Board action is expected this summer with funds going out next fall or shortly thereafter.

$70 Million Alpha Stem Cell Clinic Project Garners Mainstream Media Attention

California's $70 million plan for a chain of “Alpha” stem cell clinics today received its first major attention from the mainstream media.

The story came in the state's largest circulation newspaper, appearing this morning on the home page of the website of Los Angeles Times.

The Alpha project would create five clinics around the state and a coordination/information center under a concept that comes before the governing board of the state's $3 billion stem cell agency at its meeting tomorrow in Burlingame, Ca. Funds could be awarded as early as a year from now. (For more information, see here and here.)

Reporter Eryn Brown quoted Natalie DeWitt, special projects officer for CIRM, as the stem cell agency is known, and Maria Millan, a CIRM medical officer. Brown wrote,

“Clinics to conduct trials of stem cell therapies have different needs than clinics designed to deliver conventional therapies, DeWitt and Millan said. They need special facilities for handling the cells safely, as well as imaging equipment to track the cells once they're delivered into a patient’s body.  Some of this infrastructure already exists, but other parts of it still need to be perfected.  Establishing clinics to house multiple trials might create the critical mass needed to get the infrastructure in place, they said....

"Additionally, they said, CIRM hopes that such collaboration would encourage stem cell companies to share information -- speeding their own work and also helping out policymakers and insurers who are trying to figure out how they'll pay for stem cell therapies in the future.”

The Times quoted the California Stem Cell Report as saying last week,

 “The Alpha clinics are aimed at creation of a sturdy foundation for the stem cell industry in California, capitalizing on the burgeoning, international lure of stem cell treatments.”

The proposal envisions Alpha stem cell clinics at major, established institutions around the state. It is possible that two could be located in the Los Angeles area at institutions such as UCLA, USC, Cedars-Sinai or the City of Hope, all of which have representatives on the stem cell agency's governing board. Other likely locations are in the San Francisco Bay area and San Diego, again at facilities such as Stanford, UC San Francisco and UC San Diego that have representation on the agency board.

Institutions competing for the grants, including businesses, will be subject to closed-door. peer review prior to final action by the full governing board.  

Inside the Business in California's $70 Million Alpha Stem Cell Clinic Proposal

Want to know more about the business aspects of a $70 million proposal to create a chain of “Alpha” stem cell clinics in California?

More details can be found in a report from the California stem cell agency titled “Alpha Stem Cell Clinics: Delivering a New Kind of Medicine.”

Among other things, the 23-page report discusses how the plan would guide efforts to build profits into stem cell therapies and to develop strategies to attract investors and philanthropists. Not all of the business questions are answered. However, the report does paint a more complete picture of how the clinics would lead to actual production and marketing of a therapy. Overall, the proposal is aimed at creating a sturdy foundation for the stem cell industry in California, one that surpasses anything found elsewhere in the world.

The stem cell agency's governing board is set to move forward on the Alpha clinics at its meeting on Thursday. This week's action involves approval of the concept with an RFA coming in October. Awards to six recipients could be made as early as July of next year.

The business aspects of the proposal are critical because without a clear pathway to profits no stem cell therapies will be available on anything approaching a significant scale. 

CIRM President Alan Trounson first advanced the Alpha concept two years ago. Last fall the $3 billion agency brought together 70 folks from the stem cell world to ponder the idea and to make suggestions. CIRM's report on the discussions at the workshop served as the basis for the proposal to be considered by its governing board this week. Here are excerpts from the report.

“Workshop participants...emphasized the need for engaged experts who can consider and implement strategies for reimbursement (i.e.generating profits) for stem cell therapies, and to gather evidence for their value and effectiveness that will be important for coverage by payers. Having clear pathways in place will help in building financially sustainable clinics as stem cell therapies gain approval and are implemented as standard medical practice. The Alpha Coordinating Center (funded at $15 million) would work with Accountable Care Organizations (funding gouprs that tie performance to payment) and multi-stakeholder collaborations to generate evidence for informing coverage and payment policies.”

“Incentivizing company sponsors of clinical trials to participate in data sharing will be challenging, and it will be important to protect their interests as appropriate, by respecting confidentiality of proprietary information, while at the same time requiring an appropriate degree of data sharing to advance the mission of the Alpha Stem Cell Clinics Network(five clinics funded at $11 million each). It is interesting to note that at this time, the landscape of disclosing clinical trial results is in flux, and there is increasing international pressure for companies to disclose information on safety and efficacy to the research and medical communities.”

“Alpha Stem Cell Clinics will create unique models for assessing the financial viability of stem cell therapies in a clinical setting. Cost and revenue data may serve as the basis for developing reimbursement options among the public and private sector as therapies accumulate. Identification of reimbursement options can reduce investor uncertainties and encourage further investment by pharmaceutical companies, investors, funding agencies and philanthropists.
“The elements of the Alpha Stem Cell Clinics Network, namely the clinical sites and central coordinating center, will interact with external entities to generate revenue streams that would ultimately ensure financial sustainability independent of CIRM funding (Figure 3).”

“The Coordinating and Information Management Center could develop a fee for service model for its consulting services, and operate like a CRO. Sponsors could choose whether to use the consulting services and whether to use the Alpha Stem Cell Clinics Sites. The Alpha Stem Cell Clinics Sites would generate operating revenue by running the clinical trials and could perhaps support the Center with revenues, as the volume of trials grows and the Network builds steam.

“In a second model, clinical trial sponsors would all contract with the Coordinating and Information Management Center, which would then set prices according to services needed. From this revenue, the Center would pay the Alpha Stem Cell Clinics Sites for costs associated with the clinical trials.

“By the time the CIRM seed money is depleted, the clinics should have established a strong track record and brand for excellence in conducting clinical trials in stem cell therapies, which would attract more clinical trial sponsors, including companies. To have the largest possible impact on healthcare, it will be desirable to increase industry involvement for cell therapies. However engaging corporate involvement could be challenging, given that many cell therapies are not considered patentable, and many of the ongoing trials are conducted in academic settings. It was suggested that the Alpha Stem Cell Clinics Network align as much as possible with corporate “mentality” to maximize corporate participation.

“Overall, the Alpha Stem Cell Clinics Network will help companies increase their 'bandwidth' and run stem cell therapy clinical trials more effectively and successfully. Many companies will already have sufficient in-house expertise for administration and regulatory guidance, and may not need to engage the Center’s consulting services. They would be attracted to the Alpha Stem Cell Clinics Network because of advantages for clinical trials such as benefiting from the collective databases, know-how and experience of the 'brain trust,' positive interactions and lines of communication with the FDA and regulatory experts, positive branding, quality control, accreditation for their trials, access to patient registries for outreach and patient recruitment and, through its clinical trial management resources, help with enrollment.

“Workshop participants also emphasized that attaining reimbursement for stem cell therapies will be necessary for delivering approved therapies into medical practice. It is likely that the business models for at least some of the clinics will resemble bone marrow/HSC transplant clinics, where for stem cell therapies that are proven superior to the standard of care, the clinic will directly receive reimbursement from insurers for the procedure and follow-up care.

“Reaching this point will require advance advocacy and preparation, and the engagement with the CMS at an early stage of product development. It was recommended that the Alpha Stem Cell Clinics Coordinating and Information Management Center should employ experts in reimbursement methodologies to facilitate entry of approved products into healthcare delivery. One workshop participant, Jeff Sheehy(a stem cell agency board member), suggested that early engagement with Accountable Care Organizations (ACOs) could be helpful, given that stem cell therapies offer the promise of cures, which in the long run will offer high value and effectiveness, albeit with ' high front end costs and the necessity of developing the appropriate infrastructure for delivering complex cell based procedures.' Consortiums such as the Green Park Collaborative are being established to develop methodological standards to demonstrate the effectiveness and value of new technologies. These data could be used to inform healthcare payers of the overall benefits of cell therapies and their long-term value, as compared with existing therapies."

“In 2016 and beyond, CIRM will initiate the 'Delivery' phase, in which priorities will be 'facilitating commercialization (and non-commercial adoption, where appropriate) of therapies, advancing therapies to patients, and enabling business models for stem cell-based therapies.' Connecting this network to other networks and centers with a similar mission outside of California will further accelerate the development and delivery of stem cell therapies, through the global exchange of information and expertise. International testing of experimental therapies developed in California will be essential for ensuring their sustainability, as regulatory approval and widespread delivery of these products in major markets throughout the world will ensure commercial viability and sustainability of companies and universities that produce them, which will in turn help deliver returns to investors. Ultimately, establishing a solid foundation for investor engagement will ensure the viability of stem cell therapies as they move into clinical practice.'”

California's $70 Million 'Alpha' Stem Cell Clinic Plan Headed for Approval Next Week

Alpha clinic organizational diagram
Graphic by CIRM

California's stem cell agency next week is likely to approve a $70 million plan to build a taxpayer-financed chain of  “Alpha” stem cell clinics in what could be a major step towards making California the stem cell capital of the world,

The proposal would create five centers at existing institutions or businesses to be funded at up to $11 million each over five years. Also proposed is a coordination and information center that would receive $15 million over five years.

A story in Nature Medicine said that the Alpha clinics would be the first-ever “clinical trials network focused around a broad therapeutic platform.”

The clinics are expected to draw stem cell projects from the around the world as well as those funded by the $3 billion California stem cell agency. The proposal would be one of the largest single research efforts funded by the agency, formally known as the California Institute for Regenerative Medicine (CIRM) and use about 10 percent of its remaining cash.

The Alpha clinics are aimed at creation of a sturdy foundation for the stem cell industry in California, capitalizing on the burgeoning, international lure of stem cell treatments. Indeed, one of the objectives of the information center is to divert people from dubious treatments elsewhere.

The plan would fill a “profound gap” in quality information about stem cell treatments, according to a CIRM document, which said,

“By providing this resource, the public and potential patients would be better educated and informed, whether or not they should opt to enroll in clinical trials or approved treatments at any of the Alpha clinics.”

The Alpha concept was first broached two years ago publicly by CIRM President Alan Trounson, a pioneer in IVF research and the IVF business. His proposal has received early and heavy attention on the CIRM website with a video, blog items and a white paper.

The plan has received little critical attention although a researcher from an institution that could be a candidate for an Alpha clinic commented harshly in May on the California Stem Cell Report, calling the proposal “an irresponsible waste”and a “boondoggle for some medical schools.” The researcher, who asked that he/she not be identified, said,

“CIRM will pay for an unneeded infrastructure that will be empty space and staff sitting on their hands 99 percent of the time.  Or worse yet, CIRM will pay but the space will be used for other things, other clinic procedures paid for by insurance.”  

Elie Dolgin's July 8 piece in Nature Medicine quoted Mahendra Rao, director of the Center for Regenerative Medicine at the US National Institutes of Health (NIH), as applauding the concept. However, Rao said he doesn't anticipate the approach being tried nationally soon.

Dolgin wrote,

“Rao regularly asks researchers hoping to advance promising stem cell therapies whether they require additional clinical infrastructure. 'So far, what they've told us is they'll let us know if they need anything more than (the) programs that we have already established,' he says.”

The question of the size of the demand for Alpha clinics is not addressed in the CIRM concept plan. Also absent is much discussion of the business aspects of the proposal. It does mention “corporate sponsors” in passing. In a CIRM blog item yesterday, Natalie DeWitt, special project director at the agency, touched on business elements, declaring,

“(The proprosal) will yield better clinical trial design, accelerated approval of high quality treatments, and data and know-how to inform regulatory and reimbursement decisions.”

Reimbursement is the industry euphemism for creating ways to generate profits for stem cell firms.

The proposal said applicants would have to bring substantial support from their own institutions and “demonstrate the potential to bring in a pipeline of additional stem cell-based therapeutic trials as well as future funding streams to sustain the clinic.” Applicants would also be “evaluated in their ability to create a positive 'brand' that would attract clinical trials.”

Also up in the air was whether grant reviewers, all of whom come from out-of-state, would have special expertise to evaluate the business aspects of each applicant's proposal along with their business track record.

What is before the CIRM directors July 25 at their meeting in Burlingame, Ca., is a request for approval of the concept, which would be fleshed out for the RFA. The governing board almost always approves staff concepts, although they may modify them slightly. A number of directors come from institutions that are likely to be applicants in the program. They can participate in voting on the concept plan but would be barred from voting on any applications that come in later. The two RFAs could go out as early as October with approval of funding of applications one year from now.

In addition to the Burlingame meeting site, members of the public can participate from two teleconference locations in the Los Angeles area. The specific locations can be found on the meeting agenda.

The California Stem Cell Report will provide live coverage of the entire meeting, filing reports as warranted based on the Internet audiocast.

Here are excerpts from CIRM's staff document on the plan.

“To accelerate therapeutic development and delivery of stem cell therapies, CIRM proposes establishing the CIRM Alpha Stem Cell Clinics Network (CASC Network). The network will be designed to support projects emanating from CIRM’s funding pipeline, as well as scientifically outstanding stem cell products being developed worldwide and brought to California. Conceptually, the CASC Network is intended to be a sustainable infrastructure designed to support academic- and industry-initiated clinical trials, and delivery of therapies proven safe and effective.”

“The major thrusts (of the overall plan) will be:
• Development of clinical capacity and associated resources designed to support the effective implementation and execution of clinical trials and delivery of registered stem cell therapies
• Compilation of data and information concerning clinical trial experience and therapy outcomes to further inform the research, regulatory, and general community about the status of investigational stem cell interventions and long-term outcomes
• Dissemination of information to the public and counseling of patients and potential trial subjects about therapeutic options and clinical trials involving stem cells in the network and elsewhere.”

“The long-term vision is for the Alpha Clinics to expand and accommodate a broad array of stem cell-based clinical trials, where the trial meets the scientific, clinical trial design and ethical standards set forth by the Alpha Clinics Network, as well as FDA approved treatments.”

The coordinating and information center would be expected to :
“Build relationships with Accountable Care Organizations, and participate in initiatives for informing coverage and payment decisions
“Design strategies to attract investors and philanthropists to CASC network
“Create business plans, and marketing and branding strategies for financial sustainability of the Alpha Clinics Sites and (the coordination/information center)”.