From Cystic Fibrosis to Zika: California Awards $21 Million for Stem Cell Research

The California stem cell agency last week approved nearly $21 million for research to tackle afflictions ranging from cystic fibrosis to Zika.

Awards were made to only 11 researchers although the agency's reviewers had earlier approved 14 awards totaling $25.5 million. The governing board, however, had allotted only $21 million for the awards, and it decided to stick to its budget.

The awards are part of an effort by the agency to finance projects that can move forward rapidly within the next two years.

Six scientists sent letters to the board prior to the meeting discussing details of their research and dealing with concerns of the agency's reviewers, who approved awards earlier in a closed-door session, prior to ratification by the board.

Here are links to letters of each researcher: Rosa Bacchetta, Stanford, application number DISC2-
09526; Tejal A. Desai, UC San Francisco, DISC2-09559; Mark Mercola, Stanford, DISC2-09542 (rejected); Julie Sneddon, UC San Francisco, DISC2-09635; Jin Nam, UC Riverside, DISC2-09645 (rejected), and Matthew Porteus, Stanford, DISC2-09637.

Reviewers rejected any application that scored below 85. All of the three applications denied by the board stood right at the cutoff line with scores of 85. Mercola was the only one of the three to write a letter to the board. The agency did not disclose the names of the other two on its web site since they had not written a letter, which is a public record. The Nam application scored 84 and was not recommended for funding by reviewers.

Here is a link to a document that contains summaries of the reviews of all applications scored at 65 or above.

Here is a link to the agency's press release that contains the names of all the winners and a one line summary of their research. More details can be found in the summaries of the reviews.

Latest Targets of the California Stem Cell Agency: $26 Million for Zika, Heart Disease and Much More

The California stem cell agency next Thursday expects to award nearly $26 million to 14 scientists to seek therapies for afflictions ranging from cystic fibrosis to Zika.

The awards have all been approved by the agency's out-of-state reviewers in a round called "Quest." The $3 billion agency's board is scheduled to ratify reviewers' decisions at a telephonic meeting next week. The board almost never overturns its reviewers' decisions.

The expected outcome of a Quest award is "a candidate therapeutic, medical device, diagnostic or tool that is ready for translational stage activities."

The application receiving the highest score, 95, is seeking to develop "CRISPR/Cas9 mediated FOXP3 gene editing in patient-derived hematopoietic stem cells as a cure for IPEX syndrome."

The review summary on the $1.1 million proposal said,

"Using CRISPR/Cas9 gene editing, we will insert a wild type copy of the FOXP3 gene into patient derived HSCs, enabling pre-clinical proof of concept data for clinical trials that could reduce IPEX patient pathologies. This work will the first-in-man demonstration of the curative potential of edited HSCs and will help maintain California’s lead position in stem cell research and cure."

IPEX syndrome is a rare disease that can lead to diabetes and severe enlargement of secondary lymphoid organs.

The Zika award received the second highest score, 93. It is aimed at determining the "the impact of the Zika virus during human neurodevelopment and to test a FDA-approved therapeutic candidate to treat Zika infection." The research is budgeted for $2.1 million. 

The largest award, $2.4 million, is aimed at a gene therapy to "regenerate heart muscle for the 23 million adult and pediatric patients with heart failure, for whom there are currently no disease-modifying therapeutic approaches."  It received a score of 88.

The cystic fibrosis application was scored at 85, which was right at the cutoff line for funding. The proposal is aimed at "genome editing to correct cystic fibrosis mutations in airway  stem cells."  The application sought $2.2 million.

The reviews of 14 applications can be found here along with the reviews of unsuccessful applicants who scored from 84 to 65. None of the names of the applicants have been released yet by the agency, which withholds the information until after the board ratifies the reviewer decisions. 

Here is a link to the agenda for the meeting, which includes remote locations throughout the state at which the public can participate in the meeting and speak to the board. The meeting is also expected to be available through an audiocast. 

Remote locations include Oakland, San Diego, Napa, Irvine, Los Gatos, Elk Grove and San Francisco. Specific addresses can be found on the agenda.  

Openness and Transparency: Backsliding at California Stem Cell Agency

Highlights
$34 million Alpha Clinics involved
Information failure on proposal
Discourages public/researcher participation
California’s stem cell agency this past couple of weeks skidded significantly backwards in its efforts to improve clarity and transparency in its $3 billion operation.

The latest example came this week and involved its ambitious, $34 million Alpha stem cell clinic program at four major California institutions: the City of Hope, UCLA and UC Irvine and UC San Diego. 

A proposed, multimillion dollar project involving the effort was scheduled for action next Tuesday by the Science Subcommittee of the agency’s governing board.  As of early this morning -- only one full business day from the meeting -- the agency had released only nine words about it to the public. Here is the full text:

“Consideration of concept plan for Alpha Clinics Accelerating Center.” 

Opaque is the only way to describe the process. And it was bound to create issues with affected parties, which it has in this case.

Such cryptic notices make it impossible for the public to comment intelligently or otherwise, given the lack of information. The failure to provide the information in a timely fashion also feeds suspicion and distrust.

Clarity is one of the watch words that Randy Mills has invoked in his 15-month tenure at the California Institute for Regenerative Medicine(CIRM), as the agency is formally known. He has done much to sharpen CIRM’s focus and provide additional clarity through his analysis of the agency’s work.  

But failing to provide material in a timely fashion removes more than the shine on his efforts. The meetings of the agency’s directors are CIRM’s most important public events.  They are where patients, advocates, researchers, biotech executives and even the unwashed public can come together to hear and see the board in action and discuss issues informally with directors and the CIRM staff. Attendance should be encouraged – not discouraged. Which is what happens when important information is withheld from the public.

Last Friday the California Stem Cell Report carried an item on another mysterious agenda item, one that involved forgiveness of agency loans and potential royalty revenue, something that was promised in the election campaign that created the agency in 2004. 

That too was a case of missing information until it was much too late for the public or affected parties to make thoughtful comments. (See here and here.)

CIRM can and should do better than this. 

(The California Stem Cell Report this morning asked CIRM for comment on the failure to provide information on the Alpha proposal scheduled for Tuesday.  About ninety minutes later, CIRM spokesman Don Gibbons responded, saying that the item was now being postponed "to allow more time for refinement and consideration.")

(By this afternoon, the agency had also posted the first explanation of another cryptic item on the Tuesday agenda for the Science Subcommittee. This one would eliminate the specific schedule for RFAs in the upcoming basic research (discovery) and translational RFAs. The reason for the change is to provide more flexibility.)

(Editor's note: The last paragraph of this item was added several hours after the original posting.)

Sunlight on California's Stem Cell Loan Effort; Info Missing on Changes in $127 Million Research Programs

Highlights

Some details on loan changes

New Alpha clinic center proposed; no details

Unspecified changes upcoming in $93 million award programs

A little sunshine popped up over the weekend on a bit of fiscal alchemy at the $3 billion California stem cell agency, and a little clarity emerged.

The matter involves the agency’s loan program, which affects multi-million awards to businesses. The awards are called loans but are forgiven if no viable product emerges.

The matter surfaced as a result of a cryptic agenda item for Thursday’s meeting of the agency’s directors’ Intellectual Property Subcommittee. Here is what happened:

About a week ago, the agency posted the agenda for the meeting. The agenda contained a 24-word line that said that it was going to change its policies “to permit existing loan recipient whose loan has been forgiven to convert its award to a grant.”

The need for change and its financial impact on the agency was not discussed. The specific language being changed was not spelled out. The timetable for the changes was not specified. Nor was it discussed whether the move was desired by any recipients of the agency’s largess.

Given the opaque nature of the agenda item, the California Stem Cell Report carried an item Friday morning that said,

“In just four business days, the $3 billion California stem cell agency is going to perform a bit of financial alchemy. But like most alchemists, its methods are less than transparent.” 

Much later that day or possibly early Saturday, the agency posted a brief memo and regulatory language that provided a better look at the loan rule changes, which could have an impact on royalties the state might receive on a successful stem cell therapy.

Based on what is now on the agency’s Web site, the proposal would clarify what happens if a loan-financed therapy is dropped and then revived, leading to actual revenue. Under existing rules, such a situation could trigger an ambiguous financial burden that would have to show on the company books. And business executives and investors do not like ambiguous financial burdens. 

The memo from the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, said,

“To provide clarity regarding future obligations, CIRM proposes giving existing loan recipients whose loan has been forgiven by CIRM the option to convert their loan to a grant and forego reinstatement of a forgiven loan. In this way, loan recipients will be automatically governed by the revenue sharing (and other) principles of the agency’s intellectual property regulations in the event future revenue streams are realized. This will be particularly important in the event future revenues are realized after CIRM has exhausted its funding.” 

The directors’ subcommittee is likely to approve the change on Thursday. It would then go to the full board at its Sept. 24 in San Diego for action before it enters the state’s regulatory process, which will open it to further public comment.

The Thursday meeting will also take up changes in the “loan election policy” for this year’s $100 million clinical award program. Details on that are still not available as of this morning, but one assumption would be that they are an extension of the proposed loan changes to that particular program.

The weekend’s memo on the loan changes was dated  Aug. 20.  One can only assume that it was lingering on some CIRM executive’s desk for eight days until it was made available to the public, researchers and likely affected businesses.  

Problems with timely posting of agenda material are not new to the agency. In the more distant past, they were significant but have diminished. That is, until this case and others earlier this year.

The agency also has another directors’ subcommittee coming up in just five business days. The session involves two significant, multimillion dollar programs. One proposal calls for creation of an “Alpha Clinics Accelerating Center” in connection with the $34 million Alpha clinics effort.

The other proposal before the Science Subcommittee deals with unspecified changes in the agency’s upcoming, $93 million “discovery and translational” award rounds.

This morning, no additional details were available on those two matters.

The Science Subcommittee teleconference session on Sept. 8 will be based in San Francisco. Interested parties can weigh in at public locations in Irvine, La Jolla, Los Angeles and Duarte. Addresses are on the agenda.

The meeting Thursday of the Intellectual Property Subcommittee is also a teleconference session based in San Francisco. Public locations are available in San Diego, Hawaii, Woodside and Redwood City with two in San Francisco.

The only public access to these meetings is at their physical locations. No participation is available via the Internet.  However, comments may be submitted in advance or later by emailing them to mbonneville@cirm.ca.gov.

California Ready to Approve $243 Million for New Stem Cell Research

CIRM President Randy Mills uses a railroad analogy for therapy development

The California stem cell agency Thursday is set to approve $243 million to finance everything from testing therapies on patients to exposing high school students to research.

The multi-faceted effort will come before the 29 directors of the agency at their meeting on Thursday at the Oakland Marriot City Center. The initiatives have already cleared the directors’ Scientific Subcommittee.

The effort is the second installment in the CIRM 2.0 program begun earlier this year by the agency’s president Randy Mills. He assumed his post in May 2014 at the California Institute of Regenerative Medicine or CIRM, as the $3 billion agency is formally known.

Mills has described his changes as radical. He says they are aimed at improving the quality of applications and speeding development of therapies. He also has called for deeper involvement by the agency in the direction and work of researchers.

Mills, who has made his entire career in the biotech business, says he wants to provide a relatively smooth track, a “continuous, predictable pathway” from basic research to clinical applications. He uses a railroad analogy to illustrate the desired progression of research(see graphic above).

The $243 million up for approval this week is about 30 percent of the agency's remaining $800 million. However, the money will be spent over the next several years -- not just this year. Under Mills' spending projections, the agency will not run out of cash until 2020. 

The largest program coming before CIRM directors this week is $100 million during 2015-16 for more advanced research related to clinical development. Directors earlier approved $50 million for the effort for the first six months of this year. However, they have awarded only $25 million as of the end of June.

Another $53 million is set for a variety of mostly basic research, which Mills calls “discovery.” Requests for applications are scheduled to begin late this summer or fall. Some of the rounds will have application openings twice a year.  Cash is scheduled to flow to researchers within about 10 months of application.

Mills is also asking the board for substantial delegation of authority to him during the reviews and is calling for an “optimized review process” because of a high anticipated volume of applications in discovery.

Under the $40 million translation research round, Mills would also be delegated authority in the grant review process to pluck out applications and advance them even if reviewers disagreed. Applications will be accepted in September and March. Cash will flow to researchers about nine months after applications are submitted.

Both the discovery and translation rounds are open to both businesses and nonprofit enterprises.

A revised training program called “Bridges 2.0” for college level students is budgeted for $46 million over a five-year period. A training program for high school students, changed and rebranded as “Spark,” will receive $4 million over five years. Applications for that program are due Oct. 1. It is open to colleges, universities and non-profit academic institutions. 

Applications for the Bridges program are also due Oct. 1. They will be limited to “California public universities or colleges or private, nonprofit academic institutions, which did not receive a CIRM-funded Major Facility or Shared Research Laboratory Award (and, hence, do not have a major stem cell research program or a critical mass of stem cell researchers).”

In addition to the Oakland location of the directors' meeting, the public can participate at teleconference locations in San Diego, South San Francisco, Stanford and two in La Jolla. Addresses can be found on the agenda, which includes directions for listening to the Internet audiocast of the meeting.

Email comments for the CIRM directors on items on the agenda may be sent to mbonneville@cirm.ca.gov.