With more than 3.0 million page views and more than 5,000 items, this blog provides news and commentary on public policy, business and economic issues related to the $3 billion California stem cell agency. David Jensen, a retired California newsman, has published this blog since January 2005. His email address is djensen@californiastemcellreport.com.
Wednesday, July 25, 2012
Live Coverage for Tomorrow's Board Meeting of the California Stem Cell Agency
The California Stem Cell Report will
provide gavel-to-gavel coverage of tomorrow's meeting of the
governing board of the $3 billion California stem cell agency. Among
other things, the board is scheduled to give away anywhere from $113
million to $243 million to help push research into the clinic. Stories will be filed as warranted, based on the Internet audiocast. Instructions for listening directly to the audiocast can be found on the agenda. The meeting is scheduled to begin at 9 a.m. PDT in Burlingame, Ca., with
remote teleconference locations in Los Angeles, La Jolla and
Pleasanton. The public can participate and comment from those
locations. Addresses can be found on the agenda.
Tuesday, July 24, 2012
Record Appeals by Researchers in Huge California Stem Cell Agency Round
The California stem cell agency's
latest grant round – which is budgeted for $243 million – has
drawn an extraordinary and record outpouring of appeals from more
than half of the scientists rejected by the grant reviewers.
Nine of the 15 applicants who were
turned down have filed appeals to the governing board for its meeting
Thursday in Burlingame. No other CIRM grant round has drawn
as high a percentage of appeals, formally known as extraordinary
petitions. (See here
for a story on the previous record for percentage of
appeals.)
Only six applicants were approved for funding in the second of the agency's signature disease team rounds.
Their applications totaled $113 million, although $243 million was
allotted by the board, which would make it the largest in the
agency's history. The round is aimed at bringing
proposed clinical trials to the FDA for approval or possibly starting
trials within four years.
The rejected applicants come from both
biotech firms and nonprofit institutions, including at least two that
are ready to begin clinical trials next year, a much-sought goal of
the stem cell agency.
The appeals, posted late yesterday on the CIRM web site,
deal mainly with the details of the research although they also say,
in some cases, that reviewers did not grasp the facts or were dealing
with information that is now outdated. Here are some samples of what
the applicants had to say in their petitions.
Linda Marban, CEO of Capricor, Inc.,
said her firm's heart disease therapy proposal, which was rejected by
reviewers, is set for a clinical trial beginning next year. She said
that since the time of the review last April the firm has “made
major advances in both our clinical development program and our
management and operational team.”
Marban noted that Frank Litvack,
former CEO of Conor Medsystems Inc. of Menlo Park, Ca., is now
executive chairman of the Capricor and will provide “experienced
operational leadership.” In June 2011, Litvack was nominated to chair the CIRM board. However, directors chose J.T. Thomas, a Los
Angeles bond financier who has filled that post since then.
In another appeal, researcher Stuart Lipton of Sanford-Burnham said,
“Some reviewers were concerned about the PI's (principal investigator's) lack of experience in developing a cell therapy for clinical transplantation. Reply: Since there is currently no FDA-approved stem cell product for transplantation therapy for (the) brain, no PI could possibly have the experience requested here.”
Alexandra Capela of StemCells, Inc.
said reviewer comments on her application “were inconsistent with previous guidance provided by CIRM.” She said
reviewers “objected to a clinical approach that was already supported by the CIRM in a successful early translational research
grant and the planning grant(for her application).” Capela said
this “contradicts previous acceptance of this strategy by CIRM and
constitutes a central reason for our appeal to the (CIRM board).”
Henry Klassen of UC Irvine said
reviewers “overlooked facts” in his application and “had no real way of gauging
the extraordinary rate of our progress.”
He said trials are already scheduled for next year, far earlier than
time frames set up in the RFA for this round.
In addition to the written appeals,
scientists can appear before the full board at its meeting and often
have. Sometimes they bring patients, who make emotional presentations. The board does not have to discuss any of the appeals. Unless a
board member makes a motion on an appeal, it does not even come up for a vote. Directors are generally reluctant to approve an appeal. Here is a link to a CIRM description of the petition process.
Here is a list of researchers appealing
their rejections along with links to their appeals. The list is in
the order in which CIRM posted them on the board agenda. The review
summaries for all the grants can be found here.
For more on the CIRM grant appeal
process, see here.
Monday, July 23, 2012
California Stem Cell Agency Shy This Week on Openness
In the past year, since J.T. Thomas has
served as chairman of the California stem cell agency, the $3 billion
enterprise has done well in providing the public with important
information about matters that come before its governing board – a
welcome change from the grievously
deficient past performance.
However, that new, high standard for
openness and transparency is coming up short this month.
With less than three days remaining
before Thursday's
meeting of the governing board, important information
remains missing on significant matters scheduled to be discussed
later this week in Burlingame.
At the top of the list is the response
by CIRM President Alan Trounson to the first-ever
performance audit of the nearly eight-year-old agency. The $234,944
study said the agency is laboring under a host of problems, ranging
from protection of its intellectual property and management of
its nearly 500 grants to an inadequate ability to track its own
performance. Trounson's response could have come much earlier than
this week, even last May when the results were unveiled publicly, although the agency had been briefed privately on them still earlier.
Also missing from the agenda is an
important update on what Thomas has called a “communications war”
– shorthand for the efforts by CIRM to generate more and favorable
news coverage of the agency along with solidifying support among its
constituent groups. The agency's weak PR effort, which is now
improving, has troubled many directors for some time. The CIRM story
is critical to the agency's financial future as it looks to
private funding to continue its life beyond 2017 when its money runs
out.
Also not be found is an explanation of an
item before the directors' Science Subcommittee on Wednesday evening
that appears to have interesting implications, given CIRM efforts to
embrace the biotech industry more warmly. The proposal calls
for establishing “responsible budgeting as a criterion
for evaluating applications for funding.” No further information is available. But one wonders whether the proposal could reflect CIRM's unfortunate experience with Geron, which signed
a $25 million loan agreement with CIRM last summer only to dump its hESC program a little more than three months later. Geron cited
financial reasons. One also wonders whether the need to focus on
“responsible budgeting” reflects problems with some researchers
or whether it is intended to help businesses pick up a larger share
of awards.
Posting details on issues to be decided by directors -- in a
timely fashion -- should be a routine matter for the agency. It is also
key to engaging the public, industry and researchers – not to
mention that it is good policy, good management and good government. Without adequate notice, it
is impossible for interested parties to comment on proposals or make
well-considered suggestions. Given the agency's improved performance
during the past year, this month's slippage may only be an aberration. We
hope so.
Sunday, July 22, 2012
From Patient Advocates to Presidents: Decision-making Roles on Billions in Research
Directors of the California stem cell
agency are moving to spell out the roles of the players who make the
de facto decisions on its $3 billion in research funding.
This Wednesday evening in Burlingame,
Ca., the directors' Science Subcommittee is scheduled to consider
delineating the functions of members of the grant review group, also known as the Grants Working Group, along with CIRM staff in connection with grant reviews. Although the full CIRM
board has legal authority to approve or reject grants, it almost
never overturns a positive decision by the Grants Working Group on an
application.
The agenda for Wednesay's meeting
contains the full text of the addition to the working group's bylaws,
but it does not say why changes are needed in the reviewers' closed-door procedures. However, from time to
time, CIRM directors have commented during their public meetings that it is
not always clear to the scientific reviewers what the full process
entails.
Among other things, the bylaws addition
spells out the role of the CIRM president, Alan Trounson, and other CIRM
staff. It says the president can participate in discussions but
cannot assign scores or vote. The president, however, has the top decision authority on grant pre-applications, which are a separate process.
The new language makes it clear
that the high-powered scientific reviewers can be expected, from time
to time, to be asked by staff to explain themselves, or as the new
bylaw phrases it, to “clarify their views or address specific
issues in order to present a complete and useful” public review
summary report to the CIRM governing board.
Also added to thebylaws would be this
language,
“Prior to governing board consideration of GWG recommendations, the president and scientific staff should consider whether there are applications which they believe warrant particularly close review by the board, or whether specific modifications may be needed to successfully execute a particular proposal.”
The bylaw change also deals the roles
of the eight patient advocates on the grant review group -- all of
whom are also members of the CIRM governing board. They play a key role during “programmatic review,” an extremely broad-ranging process.
The bylaws addition states:
“Programmatic review is led by one of the GWG (Grants Working Group) vice chairs, who is a patient advocate, or a patient advocate member designated by the vice chairs. During programmatic review, patient advocate members of the GWG join the scientist members to make and vote on programmatic motions and funding recommendations to the gtoverning board. Programmatic review is intended to allow consideration of issues beyond scientific merit, such as disease representation and societal impact. In making funding recommendations to the governing board, GWG members consider the scientific merit of each application, as reflected in the scientific score, as well as any programmatic issues raised.”
The chairman of the CIRM Scientific
Subcommittee is a patient advocate, Jeff Sheehy, who is also vice
chair of the review group and plays the leading patient advocate role
in the CIRM working group. Additionally, Sheehy, a communications
manager at UCSF and nationally known HIV/AIDs advocate, almost
invariably leads the full board discussion prior to action on grant
applications.
In addition to the meeting location,
the public can participate in the session at a teleconference site at
UC Irvine. The address can be found on the agenda.
$70 Million Translational Round Proposed by California Stem Cell Agency
The latest California stem cell
research round is expected to commit $70 million to advance “promising
stem cell discoveries toward clinical development.”
The concept proposal, expected to be
approved at Thursday's CIRM board meeting, would fund as many as 20
grants and loans. Grants would go to nonprofit entities. Businesses
would have a choice of a loan or grant, which carry different rules
regarding intellectual property.
The translational grant proposal said two categories
would be funded:
“Research that results in a stem cell-derived development candidate (DC) to treat an unmet medical need where all necessary activities to move into IND-enabling preclinical development have been completed.
OR
“Research conducted to identify and/or establish the feasibility of a potential stem cell-derived development candidate. The goal of these development candidate feasibility (DCF) awards is to achieve preclinical (in vitro/in vivo) proof of concept. CIRM is particularly interested in proposals for DCF awards that address unique new opportunities for regenerative medicine that are potentially transformative therapeutic approaches to unmet medical needs (e.g. direct reprogramming).”
The RFA is expected to be posted in
September with funding in the summer of next year.
Researcher Alert: Grant Rule Changes at Stem Cell Agency
The $3 billion California stem cell agency is changing
the rules for how it handles its grants, ranging from research
milestones and budgets to training programs and unspent
funds.
A CIRM staff memo, prepared for this Thursday's CIRM board meeting, said,
“Some of the proposed amendments are clarifying amendments and others are more substantive.”
The memo said that the changes are
intended to improve the 45-page grant administration policy and
remove provisions that are hard for the staff or grantees to
“understand and follow.” The memo said the changes were
developed after input from grantees and others.
Grant recipients and others seeking
CIRM cash would be well-advised to examine the proposed changes,
which are scheduled to be approved on Thursday at the board meeting
in Burlingame.
The modifications will then go into the
state's administrative law process and are
scheduled to go into effect in October.
Friday, July 20, 2012
Royalty Rules at the California Stem Cell Agency: Business Friendly Changes Proposed
If you are looking to follow the money
trail at the $3 billion California stem cell agency, next Thursday's meeting of its 29-member board of directors is a good place to start.
On the agenda are revisions in its
intellectual property rules, which are all about who gets paid and how much and when – should an agency-financed product generate
significant cash.
The key question about the proposed changes is whether they will generate an appropriate return for the state, given its $6 billion investment, including interest on the bonds that finance CIRM. The impact of the changes is not crystal clear. And the staff memo does not mention two important definition changes that appear to be quite business friendly.
The key question about the proposed changes is whether they will generate an appropriate return for the state, given its $6 billion investment, including interest on the bonds that finance CIRM. The impact of the changes is not crystal clear. And the staff memo does not mention two important definition changes that appear to be quite business friendly.
During the 2004 ballot campaign that
created the stem cell agency, California voters were told that the
state would share as much as $1 billion or more in royalties. Eight
years later, no royalties have materialized since CIRM research has
not yet resulted in a commercial therapy.
At next week's meeting in Burlingame,
directors will be asked to modify CIRM rules for royalties that CIRM
staff said "could be a disincentive" for business. A staff memo said the proposals would alter provisions that create "administrative challenges and uncertainty." The memo asserted
the proposed changes would ensure "a comparable economic
return to California" equal to the existing provisions.
However, the memo provided no explanation or evidence for how that
result would come about. The proposed changes could also be applied
retroactively with the agreement of CIRM and the grantee.
Currently CIRM grantees and
collaborators must share as much as 25 percent of their licensing
revenue in excess of $500,000, depending on the proportion of agency
funding for the product. The IP rules also contain a provision for
payments in the event of development of a "blockbuster" therapy.
The staff memo described how that would work.
“It provides that grantees and collaborators must share revenues resulting from CIRM funded research as follows: after revenues exceed $500,000, three times the grant award, paid at a rate of 3% per year, plus upon earning $250M(million) in a single calendar year, a onetime payment of three times the award, plus upon earning revenues of $500M in a single calendar year, an additional onetime payment of three times the award and, finally, in the instance where a patented CIRM funded invention or CIRM funded technology contributed to the creation of net commercial revenue greater than $500M in a single calendar year, and where CIRM awarded $5 million or more, an additional 1% royalty on revenues in excess of $500 million annually over the life of the patents.”
The proposed changes would exempt "pre-commercial revenues" from the state's revenue sharing, the
memo said, in order to maximize the amount businesses can "re-invest
in product development." The proportionality payment provision
would be changed to require only 15 percent of licensing revenues if
CIRM's investment is less than 50 percent and 25 percent if it is
more than 50 percent. Revenue sharing would be extended to "commercializing entities." No definition of "commercializing entities" was provided in the board agenda material, but a June version of the changes defined them as "A For-Profit Grantee and its Collaborator or Licensee that sells, offers for sale or transfers a Drug, product(s) or services resulting in whole or in part from CIRM-Funded Research."
Not mentioned in the CIRM staff memo were two new provisions in the rules involving the definition of licensing revenue and the sale of a therapy. Both could be construed as quite favorable to businesses. According to the June version of the changes, licensing revenues are defined as a figure minus "a proportion of expenses reasonably incurred in prosecuting, defending and enforcing related patent rights equal to CIRM’s percentage of support for development." The sale provision says that royalties on "net commercial revenue" are not due until received from sales in the United States or Europe. That provision would appear to exclude California from receiving royalties on product sales in most of the world, where it is easier to receive regulatory approval for sale of new therapies and drugs. (See here -- page 2 -- for royalty provision and here for definition of "first commercial sale"-- page 3.)
The existing IP regulations are
enshrined in a 2011 state law. However, the law also provided that
they can be altered by the agency, the CIRM memo said, “if it
determined that it was necessary to do so either to ensure that
research and therapy development are not unreasonably hindered as a
result of CIRM’s regulations or to ensure that the State of
California has an opportunity to share in the revenues derived from
such research and therapy development.”
The memo continued,
"The proposed amendments re-strike the balance both to ensure that industry will partner with CIRM and to ensure that the State has the opportunity to benefit from successful therapy development."
Board action next week will give the
go-ahead for posting the proposals as part of the official state
administrative rules process. They are subject to additional changes
in that process.
The agenda originally contained the full text of the changes. However, that material has been dropped from the board agenda. An earlier version can be found here and here. We have queried the agency about the reason for dropping the text in the board agenda.
(Editor's note: The agency has now reposted the version of the text of the changes that was on the agenda earlier, saying that it was having problems with its web site. For the definitions of terms, however, it is still necessary to refer to the June documents.)
(Editor's note: The agency has now reposted the version of the text of the changes that was on the agenda earlier, saying that it was having problems with its web site. For the definitions of terms, however, it is still necessary to refer to the June documents.)
Thursday, July 19, 2012
Correction
The stem cell lure item today incorrectly
said the total of the two grants was $13.4 million. The correct
figure is $12.4 million.
California's $12.4 Million Stem Cell Recruitment Lure
Directors of the California stem cell
agency next Thursday are likely to approve spending $12.4 million to
lure a couple of stem cell stars to the Golden State.
(Editor's note: an earlier version of this item incorrectly said the total of both grants was $13.4 million.)
It is part of a $44 million recruitment
program that has brought three highly regarded scientists to three
California research institutions, all of which have representatives
on the CIRM board. (See here, here and here.)
As usual, the $3 billion stem cell agency does not
identify the potential recipients in advance of the meeting or the
institutions that are recruiting them. However, if you have a modicum
of knowledge about the specific fields involved, it is likely that
you can identify them based on the information in CIRM's review summaries and some Internet searching.
One of the proposed research grants–a
$5.7 million award--would go a scientist who won raves from CIRM's
reviewers. The researcher was described as an “exceptional
scientist and one of the leading young developmental biologists.”
Reviewers gave his proposal a score of 90 and, in summary, said,
“Major strengths include the candidate's exceptional productivity and contributions to the fields of mammalian embryology and kidney development, the significance and potential of the research program, the PI's proven leadership capabilities, and the outstanding institutional commitment.”The other grant was larger–$6.7 million–but reviewers raised a number of questions about the candidate although they recommended it for funding. The review summary ranked the application at 57 and said,
“In summary, this is an application from an established leader in NSC biology to pursue research focused on disease mechanisms in PD. Strengths of the proposal include the quality of the PI, the focus of the project on an interesting hypothesis, and the leadership in basic science that the candidate would bring to the applicant institution. Weaknesses included deficiencies in the research plan, the limited track-record of the PI in PD research and an institutional environment lacking adequate support for basic science investigations.“
Last January, in a rare move, CIRM
directors rejected a $6.3 million recruitment grant with a score of
76 sought by the Buck Institute, which is not represented on the
board.
The proposals are scheduled to be acted
on at a public CIRM board meeting in Burlingame, Ca.
(Editor's note: an earlier version of this item incorrectly said the total of both grants was $13.4 million.)
Wednesday, July 18, 2012
UC Davis Researchers Score Big in $113 Million Stem Cell Award Round
Scientists at the University of
California at Davis are set to win nearly half of $113 million
expected to be awarded next week by the California stem cell agency
as it pushes aggressively to turn research into marketplace cures.
Directors of the $3 billion agency are
virtually certain to approve awards to three researchers at UC Davis,
which operates its medical school and other research facilities in
nearby Sacramento. The other three expected winners are from UCLA,
Stanford and StemCells, Inc., of Newark, Ca., a publicly traded firm.
The $113 million round is the second largest research round in CIRM's history, surpassed only by an
another, earlier $211 million “disease team” round. The latest
effort is aimed at bringing proposed clinical trials to the FDA for approval or possibly starting trials within four years. That deadline
is close to the time when CIRM is scheduled to run out of cash unless
new funding sources are developed.
CIRM is currently exploring seeking
private financing. It could also ask voters to approve another state
bond issue. (Bonds currently provide the only real source of cash for
CIRM.) In either case, the agency needs strong, positive results from
its grantees to support a bid for continued funding.
The CIRM board is scheduled to approve
the latest awards one week from tomorrow at a public meeting in Burlingame in the San Francisco area. The agency's policy is to
withhold the identities of applicants and winners until after formal
board action. The California Stem Cell Report, however, has pieced
together their identities from public records.
Here are the winners and links to the
grant review summaries, listed in order of the CIRM scientific
scores:
- Vicki Wheelock, UC Davis, $19 million, for development of a genetically modified cell therapy for Huntington's disease, an inherited neurodegenerative disorder. Scientific score 87.
- Antoni Ribas, UCLA, $20 million, for genetic reprogramming of cells to fight cancer. Scientific score 84.
- Nancy Lane, UC Davis, $20 million, for development of a small molecule to promote bone growth for the treatment of osteoporosis. Scientific score 80.
- John Laird, UC Davis, $14.2 million, for development of mesenchymal stem cells genetically modified for treatment of critical limb ischemia, which restricts blood flow in the lower leg and can lead to amputation. Scientific score 79.
- StemCells, Inc., (principal investigator not yet known), $20 million, for development of human neural stem cells to treat chronic cervical spinal cord injury. The company, founded by Stanford scientist Irv Weissman, who serves on its board, said earlier this year that it had filed two applications in this round, one of which dealt with cervical cord spinal injury. No other applicants filed a proposal for such research. Scientific score 79.
- Robert Robbins, Stanford, $20 million, development of a human embryonic stem cell treatment for end-stage heart failure. Scientific score 68.
CIRM's Grant Working Group earlier this
year approved the applications during closed door sessions. The full
CIRM board has ultimate authority on the applications, but it has
almost never rejected a positive action by the grant reviewers.
The board originally allotted $243 million for this round. Directors could reach into the 15
applications rejected by reviewers and approve any of them, which the
board has done in other rounds. In this round, three rejected
applications scored within seven points of the lowest rated
application approved by reviewers, which could lead some directors
to argue that the scores are not significantly different. One of the
three came from Alexandra Capela of StemCells, Inc., and was scored at 61. The other two and their scores are Clive Svendsen of
Cedars-Sinai, score 64, for ALS research, and Roberta Brinton of
USC, score 63, for an Alzheimer's project.
Rejected applicants also can appeal
reviewer decisions to the full CIRM board in writing and in public
appearances before directors.
Twenty-three researchers were eligible
to apply for funding, CIRM told the California Stem Cell Report.
Applicants qualified by either winning a related planning grant from
CIRM last year or by being granted an exception to that requirement
by CIRM staff. Of the 22 researchers who ultimately applied(one
nonprofit dropped out), six came from biotech businesses. Three of
those qualified through exceptions. Three other businesses won
planning grants last year out of the eight businesses that applied.
CIRM has come under fire for its
negligible funding of stem cell firms and is moving to embrace
industry more warmly.
Only one of the grants approved by
reviewers involves research with human embryonic stem cells, which
was the critical key to creation of the California stem cell agency.
California voters established the agency in 2004 on the basis that it
was needed because the Bush Administration had restricted federal
funding of human embryonic stem cell research.
Sunday, June 17, 2012
California Stem Cell Report Going Dark for a Few Weeks
The California Stem Cell Report will be offline for the most part until about the middle of July. Its editor and publisher, David Jensen, is sailing off to the Perlas Islands south of Panama.
Parsing Geron's Stem Cell Foray: A Nature Journal Commentary
Why did Geron "fail" in its
much ballyhooed pursuit of the first-ever human embryonic stem cell
therapy?
Christopher Scott, senior
research scholar at Stanford, and Brady Huggett,
business editor of the journal Nature, took a crack at
answering that question in a commentary in the June edition of
Nature.
Following the sudden abandonment last
fall by Geron of its hESC business and the first-ever clinical trial
of an hESC therapy, Scott and Huggett scrutinized the history of the
company. The financial numbers were impressive. They wrote,
"How did Geron’s R&D program meet such a demise? After all, the company raised more than $583 million through 23 financings, including two venture rounds, and plowed more than half a billion dollars into R&D (about half of that into hESC work) through 2010.
"There are problems with being at the forefront of unknown territory. Of Geron’s development efforts, the hESC trial was the most prominent, and fraught. Therapies based on hESCs were new territory for the US Food and Drug Administration (FDA), and it eyed Geron warily. The investigational new drug application (IND), filed in 2008, was twice put on clinical hold while more animal data were collected among fears that nonmalignant tumors would result from stray hESCs that escaped the purification process. Geron says it spent $45 million on the application, and at 22,000 pages, it was reportedly the largest the agency had ever received."
The California stem cell agency also
bet $25 million on the company just a few months before it pulled the
plug. Geron repaid all the CIRM money that it had used up to that point.
Geron suffered from a lack of revenue
despite its vaunted stem cell patent portfolio. Scott and Huggett
reported that Geron received only $69 million from 1992 to 2010 from
collaborations, license and royalties. At the same time losses were
huge – $111 million in 2010.
The Nature article noted all of that
was occurring while other biotech companies – such as Isis
and Alnylam – found ample financial support, revenue and
success.
Scott's and Huggett's directed their
final comment to Advanced Cell Technology, now the only
company in the United States with a clinical trial involving a human
embryonic stem cell therapy.
"Your technology may be revolutionary, your team may be dedicated and you may believe. But it does not matter if no one else will stand at your side."
Our take: The California stem cell
agency obviously has learned something from its dealings with Geron.
The company's hESC announcement was an unpleasant surprise, to put it
mildly, coming only about three months after CIRM signed the Geron
loan agreement. Today, however, the agency has embarked on more,
equally risky ventures with other biotech enterprises. Indeed, CIRM
is forging into areas that conventional investment shuns. It is all
part of mission approved by California voters in 2004.
The dream of cures from human embryonic
stem cells or even adult stem cells is alluring. And CIRM is feeling
much justifiable pressure to engage industry more closely. All the
more reason for CIRM's executives and directors to maintain a steely
determination to terminate research programs that are spinning their
wheels and instead pursue efforts that are making significant
progress in commercializing research and attracting other investors.
The California Stem Cell Agency and an HIV Cure: Pushing for a Clinical Trial in 2014
The California stem cell agency's
leading efforts to find a cure for HIV – one tied to the famous "Berlin Patient" – received a plug today in a piece in the
state capital's largest circulation newspaper, The Sacramento Bee.
The article by David Lesher focused on
a $14 million CIRM grant to the City of Hope in Los Angeles that also
involves Sangamo BioSciences of Richmond, Ca. The team hopes to
launch a clinical trial by the end of next year.
The Berlin Patient is Timothy Brown,
now of San Francisco, who is the only person in the world known to
have been cured of HIV/AIDs. It came about as a side effect of a
blood transfusion carrying a rare mutation of a gene found almost
entirely among northern Europeans. Lesher, director of governmental
affairs for the Public Policy Institute in Sacramento, wrote,
"The possibility of curing a global pandemic like AIDS with funding from the California bond is exactly the kind of exciting potential that inspired voters to approve Proposition 71 by a wide margin. But the HIV research is also a good example of the challenge facing the state's stem cell agency as it tries to show voters that they made a good investment.
“None of the research under way will reach patients until long after the 10 years of funding by the ballot measure runs out. With the HIV project, researchers hope to be in human trials by 2014, but it is likely to be at least 10 years before they can show it might work in humans. And in the case of a stem cell cure for AIDS, it would be many years after that before a treatment is widely available.”
Jeff
Sheehy, a prominent AIDS activist and a board member at the stem
cell agency,
described the effort as "the global home run. That's not in 10
years. … But this could be the beginning of something really
amazing."
Lesher also wrote,
"Nobody thought stem cells might be used to cure HIV when the bond (funding for the stem cell agency) passed. Far from the embryonic stem cell treatments that inspired the ballot measure, the HIV research involves a new and growing integration of stem cell and genetic science."
Indeed,
the ballot initiative that created the $3 billion California stem
cell agency trumpeted its devotion to human embryonic stem cell
research, which had been throttled by the Bush Administration. The
agency has veered away from hESC research, which now amounts
to less than $450 million out of the $1.4 billion in grants approved
since 2004.
Labels:
clinical trials,
Grant-making,
media coverage
Wednesday, June 13, 2012
$30 Million Round Attracts Strong Industry Interest; More Cash Coming?
The California stem cell agency is
considering adding more cash to its upcoming $30 million award round
aimed at aiding projects that can complete – within the next four
years – a clinical trial for a therapy.
CIRM Chairman J.T. Thomas,
a Los Angeles bond financier, last month told agency directors that
there is "some real quality in the mix" among the firms
that have expressed initial interest. Depending on the judgment of
CIRM award reviewers later this year, Thomas said the board could
well be asked to increase the funding.
The "strategic partnership"
round has already exceeded expectations in terms of volume. CIRM told
the California Stem Cell Report that the agency has received
letters of intent from 37 enterprises, including 29 biotech
companies.
The round is an outgrowth of
recommendations two years ago from an "external review"
panel that said that CIRM needed to do a better job of engaging the
biotech industry. The RFA for the round said the agency's intent is
to "enhance the likelihood that CIRM-funded projects will obtain
funding for phase III clinical trials" and attract additional
financing.
Elona Baum, the agency's general
counsel and vice president for business development,, said in a news release earlier this spring,
“The Strategic Partnership Funding Program represents a new era for CIRM, one that is increasingly focused on moving therapies from the lab to the clinic, while still recognizing the importance of maintaining investments in early stage science,”
As the RFA is currently configured, CIRM
will provide grants or loans of up to $10 million to three
recipients. Applicants will have to match the size of the award. For
the first time, CIRM will also require applicants to demonstrate the
financial ability to carry the project forward.
In response to a query, CIRM spokesman
Kevin McCormack said,
"We received 37 letters of intent (LOIs), including 8 from non-profits and 29 from biotech companies. Based on the information in the LOIs, and on discussions with applicants, we were able to determine that some of the proposals were for projects that were outside the scientific scope of the RFA and that some of the applicants did not meet the minimum specified criteria in the RFA for 'Commercial Validation.' We currently expect to receive 10-15 applications for projects that appear to be eligible."
A "commercial validation"
review is scheduled for this fall by the directors' Intellectual
Property and Industry Subcommittee, which is co-chaired by
Stephen Juelsgaard, former executive vice president of Genentech,
and Duane Roth, CEO of CONNECT, a San Diego nonprofit
that supports technology and life sciences business development. The
others on the six-member panel are Chairman Thomas, Michael
Goldberg, a general partner at the MDV venture capital
firm, and two academics, Os Steward, chair and director of the
Reeve-Irvine Research Center for Spinal Cord Injury at UC
Irvine, and Susan Bryant, former vice chancellor for research,
also at UC Irvine.
CIRM's short version of commercial
validation says that applications must have "the financial
capacity to move the project through development or of being able to
attract the capital to do so. This may be evidenced by, for example,
(i) significant investment by venture capital firms, large
biotechnology or pharmaceutical companies and/or disease foundations;
(ii) a licensing and development agreement with a large biotechnology
or pharmaceutical company, or a commitment to enter into such an
agreement executed prior to the disbursement of CIRM funding; and/or
(iii) financial statements evidencing significant liquid assets."
Applications are due June 26 with
reviews in September. The directors' Industry Subcommittee will meet
following the reviews. CIRM said funding would come no earlier than
January of next year.
Tuesday, June 12, 2012
Stem Cell Agency and its $2.4 Million Legal Costs: Proposal to Add Staff Lawyer Slips Away
The California stem cell agency has
dropped a plan to add an additional lawyer to its staff on top of its
$2.4 million yearly legal budget.
The proposal was eliminated from the
agency's spending plan for the fiscal year beginning in July after it
ran afoul of complaints in April from Art Torres, co-vice chairman of
the agency, that legal spending was "awfully bloated."
At the time, CIRM's President Alan
Trounson and general counsel Elona Baum argued, however, that the
position was needed to protect CIRM's intellectual property. They
said that grantee institutions were failing to take necessary steps
to protect the IP and were putting CIRM "at risk."
The discussion occurred during a public
meeting, but was settled behind the scenes before last month's
approval of the budget by the CIRM board of directors. Instead of
containing $221,000 for salary and benefits for another lawyer, the
budget contained $203,000 for an external contract for the IP legal
work.
The issue of hiring additional staff
has implications beyond the most obvious. CIRM is laboring under a
legal budget cap that hampers its operational flexibility. Plus the
agency will move into a shutdown mode in about five years unless it
derives a new source of financing.
During the April discussion, Baum cited
a "very in-depth memo" justifying the addition of an
attorney but did not present it at the time. The California Stem
Cell Report subsequently asked the agency for a copy. The first
version that CIRM supplied consisted of a single page and was mostly
a list of tasks. It was also heavily expurgated by CIRM, although the
agency did not initially disclose that information had been removed.
The actual document turned out to be two pages long but still was
something less than in-depth.
CIRM said the information was removed
under attorney-client privilege. CIRM spokesman Kevin McCormack said
it contained "reflections and advice about particular legal
issues" from Baum to Trounson.
Our take: It is poor management to
place privileged information in what should be a routine budget
justification for adding staff. The result is a breakdown in
openness on the part of the California stem cell agency. It is not
the first time that CIRM has hidden information under attorney-client
privilege. In 2008, the agency concealed public relations advice from
a New York firm using that rationale. The matter involved an
Australian researcher "under investigation for
improprieties who worked in the stem cell laboratory run by CIRM's
incoming President Dr. Alan Trounson," CIRM said at the
time.
A final note on budget matters at the
May board meeting: With little discussion, the board approved an
overall budget of $17.9 million for coming fiscal year, an 8.5
percent increase over the estimated $16.5 million spending for the
current fiscal year. The budget calls for a handful of new hires,
raising the size of the staff of the $3 billion agency to the
equivalent of 59.
CIRM Chairman J.T. Thomas also told the
board the agency is assured of cash for its operations and research
funding through the end of this year. CIRM relies on money borrowed by
the state – general obligation bonds. However, under an arrangementarrived at last year, the funding is being provided through short-term
borrowing – commercial paper. The state expects to offer another
round of bonds this fall, but it is not clear whether CIRM bonds will
be included. Gov. Jerry Brown is adamant about reducing the cost of
state borrowing, which has skyrocketed in recent years.
Here is a copy of Baum's memo.
Sunday, June 10, 2012
Finding on 'Evil' Stem Cells Boosts Stem Cell Agency PR
The California stem cell agency, which
is struggling to spread the word about its good deeds, made a bit of
progress last week when it was praised – not once but three times –
on a widely followed national media outlet.
Jill Helms, Stanford photo |
The PR bonus occurred on Science
Friday, the NPR program that is a favorite on PBS radio stations
around the country. It has 1.4 million listeners and 600,000 podcast downloads each week.
Jill Helms, a surgery professor at
Stanford and a specialist in regenerative medicine, was the guest
last Friday. She talked about what Science Friday host Ira
Flatow called a "paradigm-shifting" finding that
cholestrol and fat are not the likely villains in clogging arteries.
Instead the villain is a stem cell – an evil one.
While evil stem cells are not a matter that is pushed by the California stem cell agency, Helms said her
collaboration began as a result of a CIRM-sponsored meeting in Japan.
Although she and lead researcher Song Li, an associate professor of bioengineering at UC Berkeley, work nearly within shouting distance,
they had never met. She said,
Zhenyu Tang (at microscope) examines vascular stem cells in culture along with Aijun Wang (left) and Song Li. UC Berkeley/Zoey Huang photo |
"Even though he works just across the (San Francisco) Bay from me - I met him at a meeting in Japan that was sponsored by the California Institute for Regenerative Medicine, or CIRM, and they fund a lot of stem cell research in California."
Later she said,
"I will tell you that cancer is certainly a disease that looks very much like a stem cell gone out of control. And so if we understand what normally regulates a stem cell's behavior, then we gain some crucial insights into what regulates maybe a cancer cell's behavior. It's that kind of approach that I think that CIRM is largely funding initiatives to try to target human diseases, the big ones, and the ones that make us all sort of quake in our shoes, and attempt to come up with new therapies."
And then still later, she said,
"Most basic scientists that work in stem cells and in the area of stem cell are trying as hard as possible to move this into translational therapies, things that can be used in humans. And, of course, CIRM, our funding institution, is very adamant about this being the trajectory. So, you know, I'll be taking a stab at it about five to seven years. I think that the ability to rapidly screen existing drugs for their ability to target this cell population is why we think that it might have a shorter course to getting into humans."
We should note that Helms has not
received a grant from the stem cell agency nor is she even one of the
featured players in CIRM's many videos. Song Li does have a $1.3million grant from the agency.
The three-pronged push by Helms is just
what the agency needs if it is to sell its efforts, which are almost
totally ignored by the mainstream media. However, the Science Friday
audience consists almost entirely of "true believers" in
the virtues of science and research. If CIRM is to accomplish its
PR-communications-marketing goals it also has to reach the unwashed
heathens, who are, however, unlikely converts. But most importantly,
CIRM needs to persuade fence-sitters. All of which will require a
long, hard and sometimes frustrating campaign.
One final note: The UC Berkley press release on the research said it was supported by cash from CIRM, the
NIH and the United States Army. According to CIRM's research blog post
on Li's work, his team included two researchers who were
part of Berkeley’s CIRM-funded training program.
Friday, June 08, 2012
Business-friendly Changes Proposed for Revenue Sharing by Stem Cell Agency
The $3 billion California stem cell
agency, which hopes to generate income for the state through the sale
of stem cell therapies, is moving to make its profit-sharing rules
more friendly to business.
The proposed changes will come up Monday morning before the Intellectual Property and Industry Subcommittee of the
CIRM governing board.
No stem cell research funded by CIRM
has yet been commercialized. Its intellectual property regulations,
which determine payback criteria, were developed shortly after CIRM
was created in 2004. Ed Penhoet, one of the founders of
Chiron and now a venture capitalist, chaired the panel that worked
out the rules. He has since left the CIRM board.
A CIRM staff memo described the payment
rules in the case of a "blockbuster" therapy as "uneven"
and "lumpy." The memo said they "could be a
disincentive for the engagement of industry." Other rules were described as creating
"administrative challenges and uncertainty." The proposed changes, the memo said,
would address those issues and ensure a "comparable economic
return to California."
Public sites where interested parties
can take part in the discussion are located in San Francisco, La
Jolla, Los Angeles and Irvine. Specific addresses can be found on themeeting agenda.
The proposed changes must go before the
full governing board and then into the state's administrative law
process before taking full effect.
Thursday, June 07, 2012
Business Success Rate at Stem Cell Agency: Zero in Latest Round After 14 Fail
California biotech companies chalked up
a zero in the latest funding round by the state's $3 billion stem
cell agency, although 14 tried to run a gauntlet that industry has
complained about for years.
All $69 million in last month's
translational research round went to 21 academic and nonprofit insitutions. No business received an award. One firm, Eclipse
Therapeutics of San Diego, appealed to the agency's governing board but was not successful despite having a higher scientific score
than at least two winners.
The miniscule amount of funding for
commercial enterprises – less than 4 percent of $1.4 billion handed
out so far – has been a matter of concern for some time for both
industry and some members of the CIRM governing board. Most
recently, industry executives complained at an April hearing of the
Institute of Medicine panel looking into CIRM's operations.
Even a 2010 review commissioned by CIRM said the agency needed to do
better by business.
The question of funding goes beyond a
simple matter of fairness or "good science," as CIRM
describes its funding goal. Without efforts by industry to turn
research into cures, CIRM will not be able to fulfill promises to
voters in 2004 when they approved creation of the stem cell agency.
CIRM last month approved a set of five-year goals that push more
aggressively for development of commercial products, but the goals
lacked such things as a financing round devoted solely to business
applicants.
In last month's translational round,
applicants went through a three-step process, which is conducted
primarily behind closed doors. First came what CIRM calls
pre-applications. Those were reviewed by CIRM staff with the help of
outside advisors if necessary. Applicants who cleared that hurdle were allowed to apply for the full, peer-reviewed round. During that
process, the CIRM Grants Working Group reviews applications,
makes decisions and sends them to the full CIRM board for
ratification and possible changes. The board almost never has
rejected a grant approved by reviewers. But the board has ultimate
authority and sometimes funds applications that reviewers have
rejected. The applicants' names are withheld from the board and the
public during the process, although some of the board discussion and
the final vote is conducted in public. CIRM does not release the
names of rejected applicants unless they appeal.
In the translational round, a total of 42
pre-applications out of 167 were approved by staff, according to
CIRM. Thirty-eight came from nonprofits and academics out of the 153
such institutions that applied. Four out of 14 business
pre-applications advanced to full applications but none made the
final cut. All of the winning applications were linked to
institutions that have representatives on the CIRM governing board.
Those representatives are not allowed to vote on or take part in
discussion involving applications to their institutions.
The primary decision tool used by the
grant review group is a scientific score. In last month's round,
scores of approved grants ranged from 88 to 53. However, eight grants
that were ranked above 53 were rejected by the board. One of those
higher-ranking applications came from San Diego's Eclipse
Therapeutics, which scored 58. The low-ranking grants were approved
for what CIRM describes as "programmatic" reasons.
More than three weeks ago, the
California Stem Cell Report asked CIRM for figures on the
numbers of applications in the translational round, including those
for business. CIRM said the figures had not been compiled and would
not be available until after the awards were made on May 24. The
numbers were finally supplied yesterday.
Our take: The number of applicants, and
their breakdown, is basic information that should be part of board's
decision-making process. The statistics should be routinely available
well in advance of the board's meeting. Indeed, the agency in its
earlier days used to routinely publish the figures. It may be now
that generating them is more time-consuming than necessary. The
recent performance evaluation of the agency said CIRM needs to make
major improvements in how it handles critical information needed for
its top management and board.
Whatever the reason, given CIRM's poor
track record with business, the agency's directors should diligently
track industry's success rate on applications. If proposals ranked as
low as 53 are approved while higher ranking applications from
business are bypassed, it warrants more than cursory examination.
Monday, June 04, 2012
'Ugly' Stem Cell Headlines and a Stem Cell Essay Contest
California stem cell researcher Paul Knoepfler has been busy recently pumping out a plethora of items on his blog, including his own stem cell essay contest and a summary of "ugly" stem cell headlines.
He also rails, albeit briefly, against the Los Angeles Times "hate fest" against the California stem cell agency and offers some advice on developments involving prostate cancer, an affliction that he suffered from a few years ago.
Knoepfler, a UC Davis scientist, puts some cash on the line in his essay contest, with a prize of a $50 iTunes card plus publication of the winning piece. He is looking for a "convincing, non-fiction essay on stem cells thinking entirely outside the box." No more than 500 words. He has two categories, one for persons under 18 and one for persons over that age. June 30 is the deadline for submissions.
Knoepfler also wrote about Twitter and how it can be used by scientists in a useful item called "The scientist's top 10 guide to Twitter." We recommend it.
Two California Stem Cell Agency Directors Plump for Proposition 29
Two directors of the $3 billion
California stem cell agency have popped up in the battle over the
anti-tobacco initiative on tomorrow's ballot in the Golden State.
They are Sherry Lansing and
Kristiina Vuori, who were the subjects of a column by Michael
Hiltzik of the Los Angeles Times dealing with Proposition
29, the "Son of CIRM" measure that would raise
$800 million for research by increasing the price of cigarettes by $1
a pack. In addition to serving on the CIRM board, Lansing heads her
own anti-cancer foundation and is chair of the board of the UC
regents. Vuori is head of the Sanford-Burnham Institute in La
Jolla.
Proposition 29 is patterned after the
measure that created the stem cell agency. The organization established by Proposition 29 would also be governed by a board that is run by
representatives of organizations almost certain to receive the bulk
of the funding, as is the case with CIRM.
In an op-ed piece on Friday, Lansing and
Vuori said the Times and Hiltzik had fallen for "a smokescreen"
put up by tobacco companies which are spending something in the
neighborhood of $40 million to defeat the initiative. Lansing and
Vuori said the measure is needed to stop smoking by young people as
well as providing cash for research for tobacco-related diseases.
Young people are more sensitive to price increases of cigarettes than
adults, according to research.
Lansing and Vuori referred to a column
in which Hiltzik opposed the measure because it would divert money
from more immediate state needs, including health and welfare
programs for children, education and the poor. (See here for thecolumn and here, here and here for related items.)
In his most recent column, Hiltzik
said,
"The...problem with Proposition 29 is its pigeonholing of the money for cancer research rather than for immediate needs here in California that are absolutely dire. It’s all well and good to say that cancer research benefits everyone, but the real question is whether it should be the absolute top priority for a state that can’t afford to keep its children fed or offer them medical care in the here and now.
"Lansing and Vuori say the fact that Prop. 29 'fails to provide funding for schools, roads or affordable housing' is irrelevant, because it was 'was never intended to solve these problems.'
"In the context of the state’s needs, this is a rather callous approach to take. Let’s spell out why, so Lansing and Vuori won’t be so inclined to dismiss these necessities of life so casually."
Hiltzik cited a list of state
government cuts that have meant the loss of health coverage for
400,000 California children, eliminated welfare benefits for 578,000
poor California families and would mean an end to state college
student aid for 72,000 young people from less affluent families.
Hiltzik continued,
"That’s just the beginning of what might be cut because the state needs money—and won’t be able to lay its hands on the hundreds of millions of dollars that Lansing, Vuori, and their research colleagues are angling for. They don’t want voters to be reminded that there are competing demands for the tobacco money, and they do so by failing to mention that they exist, and also by presenting the spending on cancer research as the voters’ only choice.
"It’s the only choice because the promoters of Proposition 29 designed it that way. Advocates of programs like this love to pass them in via voter initiatives because they leave no room to measure them against alternative needs."
A final note: The New York Times
carried a piece yesterday on Proposition 29 that drew 481 comments.
The article said,
"Organizers argued that the tax would have less chance of passing if voters thought it would go into the state coffers, and said that their only goal here was cutting down on smoking."
Also yesterday, Willie Brown, the former mayor
of San Francisco and a keen observer of California politics,
predicted voter approval of the measure along with an increase in
cigarette smuggling from adjacent states and the sale of discount
smokes at the 58 Indian casino sites in the state.
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