Stem Cell Blowback from Proposition 71


Proposition 71 last week once again
stood in the way of action by the $3 billion California stem cell
agency.

This time it was a bit of minutia
embedded in state law that prevented the agency's governing board
from going forward. The result is that the board will have to hold
another meeting in August to approve matters that need to be acted on
in a timely fashion.
The minutia involves the supermajority
quorum requirement for the board, the percentage of board members
needed to conduct business legally. Proposition 71, the 10,000-word
ballot initiative that created the agency in 2004, stipulates that 65
percent of the 29 members of the board be present for action.
Here is what happened: Late last
Thursday afternoon, CIRM directors were moving fast after a long day
of dealing with $151 million in research awards. But as they
attempted to act on proposed changes in the agency's important
intellectual property rules, one of the board members left the
meeting, presumably to catch a flight. The result was that the
meeting quickly ended after it was decided to deal with the IP
proposal and another matter during a telephonic meeting this month.
The quorum problem has plagued the CIRM
board since its inception, although the situation has eased since
J.T. Thomas
, a Los Angeles bond financier, was elected chairman in
2011. A few years back, the board also changed its rules to allow a
limited number of board members to participate in meetings by
telephone, reducing the pressure on board members to physically
attend meetings.
The obvious solution would be to change
the quorum to 50 percent, a reasonable standard. However, the board
is legally barred from doing that. To make the change would require a super, supermajority vote, 70 percent of
each house of the state legislature and the signature of the
governor. That is another bit that is embedded in state law, courtesy of Proposition 71. To attempt to win a  70 percent legislative vote would involve a political process
that could be contentious and also involve some horse-trading that
the stem cell agency would not like to see.
Why does the 65-percent quorum
requirement exist? Normally, one would think such internal matters
are best left to the governing board itself. It is difficult to know
why former CIRM Chairman Bob Klein and his associates wrote that
requirement into law. But it does allow a minority to have effective
veto power over many actions by the governing board.
Of course, there is another way to look
at the problem: CIRM board members could change their flights and
stick around until all the business is done. But that would ignore
the reality that all of them are extremely busy people and have
schedules that are more than full.
All of this goes to one of the major policy issues in California -- ballot box budgeting and the use of initiatives that are inflexible and all but impossible to change, even when the state is in the midst of a financial crisis in which the poor, the elderly and school children are the victims. One California economist has called the situation "our special hell."

Source:
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Text of CIRM Response on the Weakening of Financial Disclosure Requirements


On April 24, the California Stem Cell
Report
asked the state stem cell agency about its proposed changes
in its requirements for financial disclosures from its officials.
Here are the key elements from that query with the stem cell agency's
response following.
The agency was invited to respond to
the following: "The new code appears
to give discretion to the employee to determine what enterprise is
'the type to receive grants or other monies' from CIRM. Additionally,
it would not appear to require disclosure of an investment with or
income from, for example, Kleiner Perkins, which is a major investor
in iPierian, which holds $7 million in CIRM grants and could well be
a future applicant...(T)he weakening of the code comes at a time when
the agency is moving to cozy up to industry and looking to raise
funds to continue its existence, all of which raises even greater
conflict of interest issues than earlier in CIRM's existence."
Here is the text of the response April
25 from Kevin McCormack, CIRM's new senior director for public
communications and patient advocate outreach.

"In answer to your question, we
are proposing changes to the Conflict of Interest Code based upon
recommendations from the California Fair Political Practices
Commission (FPPC). The Political Reform Act requires state
agencies like CIRM to review their Conflict of Interest Codes every
two years.  The FPPC, which is charged with enforcing the
Political Reform Act, is responsible for reviewing and approving
CIRM's Conflict of Interest Code.  In preparation for this
review, CIRM's counsel met with the FPPC staff who suggested the
proposed amendments which are the subject of the upcoming Governance
Subcommittee meeting.  The proposed amendments to CIRM's
Conflict of Interest Code are consistent with the FPPC's position
that agencies should tailor their disclosure categories to type of
work performed by the agency.  For example, CalPERS's
conflict of interest code requires CalPERS officials to disclose
investments in, and income from, entities that are of the type with
which CalPERS contracts and entities in which funds administered by
CalPERS could be invested.  Likewise, the State Board of
Education requires its members to disclose investments, business
positions, and income from a publisher, manufacturer, or vendor of
instructional materials, or services offered to educational
institutions in the State of California and investments, positions of
management and income from any private school in the State of
California.  Similar to these codes, the FPPC proposed that
CIRM's Code be tailored to the nature of CIRM's work.  Thus,
the FPPC proposed that CIRM require its board members and high-level
employees to disclose investments in, and income from, entities that
are of the type with which CIRM would contract or from which CIRM
could procure goods or services as well as investments in, and income
from, biotech and pharmaceutical companies.  Because these
are the types of entities that are likely to create potential
conflicts of interest, we believe the disclosure categories are
appropriate.  It is important to remember, however, that
this is a preliminary proposal.  CIRM will seek input from
the Governance Subcommittee, the Board, and members of the public
before seeking approval of the amendments."

Source:
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California Stem Cell Agency Wants to Weaken Financial Disclosure for Execs and Board


The $3 billion California stem cell agency, which is moving to engage the biotech industry ever more closely, is proposing a major weakening of the financial disclosure requirements for its board of directors and executives.

The move comes as the agency is also seeking to raise cash from the private sector to continue the state research effort's existence.  CIRM's dimming of transparency runs counter to government trends nationally for more disclosure rather than less, including regulations enacted last year by the NIH.

The proposed changes will be considered next Thursday by the CIRM directors' Governance Subcommittee, which will have public teleconference sites in San Francisco and Irvine and two each in Los Angeles and La Jolla.

Currently CIRM board members and top executives must disclose all their investments and income – in a general way – along with California real property that they hold. Under the changes, disclosures would instead be required only "if the business entity or source of income is of the type to receive grants or other monies from or through the California Institute for Regenerative Medicine." CIRM offered no explanation of what it means by "of the type to receive" funds from the agency.

The proposal further narrows disclosure in connection with income or investments in enterprises that provide facilities or services used by CIRM. With the removal of the requirement for reporting all investments, CIRM's changes also specified disclosure of income and investments connected to business entities (nonprofits are not mentioned) that are engaged in biomedical research or the manufacture of biomedical pharmaceuticals.

The new code would appear to give CIRM directors and executives wide personal latitude in determining what should be disclosed. The current language simply states that "all" investments, etc., must be disclosed. That language originated in the 1974 ballot initiative that created the state disclosure requirements. The initiative's intent was to give the public and interested parties access to key information that would allow them to determine what forces are at work in government and whether conflicts of interests exist – as opposed to simply trusting the assertions of officials without additional substantiation.

The new code also appears to relieve CIRM officials of reporting investment in or income from venture capital or other firms that may be engaged in financing biotech or stem cell enterprises, since the firms do not receive cash from CIRM or engage in biomedical research.

While the code appears to provide more reporting freedom for board members and executives, it also may indirectly impose a burden on them to determine whether any of their investments may involve biomedical research or enterprises that could possibly receive funds from CIRM at some point

Earlier this week, the California Stem Cell Report asked the stem cell agency about such issues. Kevin McCormack, CIRM's new senior director of public communications and patient advocate outreach, replied that the changes were "proposed" by the state Fair Political Practices Commission, which oversees state disclosure laws.

He said the FPPC says agencies "should tailor their disclosure categories to type of work performed by the agency."

McCormack cited as examples the State Board of Education and the state retirement system.

As for the specific changes in CIRM's code, McCormack said,

"Because these are the types of entities that are likely to create potential conflicts of interest, we believe the disclosure categories are appropriate."

McCormack did not comment on whether the proposed code would give board members more reporting latitude or whether it relieve them of reporting investments tied to the financing of biotech or stem cell firms. (The text of his response can be found here.)

The California Stem Cell Report is querying the FPPC concerning its policy regarding disclosure codes. CIRM's new code is expected to go before the the full CIRM board in late May. The changes are subject to review by the FPPC and then must formally go through the state administrative law process during which the public can comment and the code modified before final adoption.

Our take? The proposed changes are not in the best interests of CIRM or the people of California. The absence of transparency and disclosure only breeds suspicious speculation of the worst sort. The agency is already burdened by conflicts of interest that are built in by the ballot measure that created it in 2004. Nearly all of the $1.3 billion that CIRM has handed out has gone to institutions linked to CIRM directors. Weakening disclosure at a time when the biotech industry will become more closely tied to CIRM inevitably raises questions about financial linkages – present and future – between CIRM directors and executives and industry. For the past seven years, CIRM directors and staff have been able to comply with
more complete disclosure. They should continue to do so for the life of the agency, which will expire in less than a decade unless it finds additional sources of cash.

Source:
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The Afterlife of the California Stem Cell Agency: Venture Philanthropy and Big Pharma


The $3 billion California stem cell agency, which is facing its possible demise in five years, is exploring an afterlife that dips into "venture philanthropy" on a national level as well as investment ties with Big Pharma.

The Golden State's unprecedented research program laid out those possibilities in a "transition plan" sent this week to Gov. Jerry Brown and the state legislature. The plan was required under a law passed two years ago. The agency's future direction was also aired at a meeting last month in Los Angeles.

The California Institute for Regenerative Medicine(CIRM) will run out of funds for new grants in 2017. Its only real source of funding is cash that the state borrows (bonds). CIRM says that only $864 million remains for new research awards, and some of its recent grant rounds exceed $200 million. The current position of the agency is that it is "premature" to consider asking voters in financially strapped California to approve another multi-billion dollar bond measure.

The venture philanthropy effort involves creation of a nonprofit organization. CIRM Chairman Jonathan Thomas said in January that he is "test-driving (the proposal) with some high net worth donors we know to be interested in the stem cell space." Thomas was addressing the Citizens Financial Accountability and Oversight Committee, the only state entity specified charged with overseeing the agency and its directors. He said,

"We're busily putting together in conjunction with a national organization called the Alliance for Regenerative Medicine the plans for a nonprofit venture philanthropy fund."

He said it would "would accept applications for awards from researchers and companies all over the country, not just those funded by CIRM, but those funded by NIH or the New York Stem Cell Foundation or the state of Maryland or whatever."

The Alliance for Regenerative Medicine is an industry-dominated lobbying group, based in Washington, D.C.  The group's executive director and co-founder is Michael Werner, a longtime pharma and health industry lobbyist, who is also a partner in the influential Washington law firm of Holland and Knight.

The "biopharma investment fund" proposed by CIRM is less well developed. CIRM said it plans to explore opportunities with companies to fund stem cell research in California. The transition document uses as an example an $85 million deal between Pfizer and UC San Francisco, which gives the company special access to biomedical research.

The transition plan also touches on other issues such as winding down grants after its new grant money runs out, along with protecting intellectual property.

The plan could be considered a marketing tool for the agency's afterlife efforts. The document devotes a good portion of its nine pages to recounting the history of CIRM and touting its accomplishments.

Thomas used the occasion of the submission of the plan as a springboard for a piece yesterday on the CIRM research blog.He concluded his item by quoting from the plan itself. CIRM's achievements during the past seven years, he wrote, "will allow California to continue world (stem cell) leadership in the coming decades."

Source:
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CEO of Biotime's Comments on Stem Cell Agency and Development of Therapies


Michael West, CEO of Biotime, Inc.of Alameda, Ca., has published the text of his prepared remarks to the Institute of Medicine panel examining the performance of the $3 billion California stem cell agency.

Here is one excerpt from the statement by West, who was also CEO at Advanced Cell Technology and founded Geron.

"To put it simply, stem cell research by itself will not lead to cures. Research and DEVELOPMENT leads to cures. In my opinion, if CIRM fails to deliver on its goal to deliver cures, it will not be a result of internal governance issues. Instead, it will be a result of inefficient capital allocation. A graphic way of visualizing my point is to say that CIRM has historically funded primarily research, and little product development, i.e. large “R” little “d”. Approximately 5% of CIRM’s expenditures have been allocated to biotechnology and health science entities whose expertise is product development, and 95% has been allocated to nonprofit institutions in the state for basic research. Human therapeutic product development in the United States requires a very intense and expensive process for approval that is primarily focused on development side of the equation. In this respect, therapeutic approvals differ significantly from the discovery and development of silicon-based technologies that have been so successfully commercialized in California."

Here is a link to the full text of what West posted on the Biotime web site.

Source:
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California Stem Cell Agency Launches $30 Million Plan to Lure Industry


Just one week after the $3 billion California stem cell agency was sharply criticized for its failure to adequately support biotech firms, the agency formally kicked off a $30 million effort to engage industry more closely.

The initiative, in the works since the middle of last year, was heralded as the beginning of a "new era" for CIRM, which is moving to transform into cures the stem cell research it has funded over the last seven years. The agency has scheduled a webinar for April 25 for prospective applicants.

CIRM's press release, crafted by the agency's new PR/communications director, Kevin McCormack, yesterday quoted CIRM President Alan Trounson as saying,

"This initiative is a major new development in the progress towards providing new medical treatments for patients by engaging the most effective global industry partners."

Elona Baum, the agency's s general counsel and vice president of business development, said the program "represents a new era for CIRM."

Under the RFA, the agency will award up to $10 million each for three grants or loans. The program, however, is not limited to businesses. Non-profits may apply as well. Representatives from industry have complained about a strong tilt on the part of CIRM towards academic and non-profit research enterprises. The CIRM board is dominated by representatives from those two sectors.

The program grew out of recommendations in November 2010 from an "external review" panel put together by CIRM that said the agency needed to do better with business. The refrain was heard again directly from stem cell firms at last week's hearing by the Institute of Medicine on the stem cell agency's performance. According to CIRM's figures, businesses have received $54 million in grants and loans since 2005, the first year the CIRM board approved grants, out of a total of $1.3 billion.

Only one news outlet has written a story so far about the posting of the RFA and the press release, as far as can be determined.

Ron Leuty of the San Francisco Business Times said,

"The most likely candidates to attract industry funding would be CIRM’s 'disease team' grant winners, who face a deadline of 2014 to bring a project to the point of first-in-human clinical trials. CIRM has weighed options for pushing those projects — there are 13 of them now — deeper into the FDA approval process."

CIRM said in the RFA material,

"The intent of the initiative is to create incentives and processes that will: (i) enhance the likelihood that CIRM funded projects will obtain funding for Phase III clinical trials (e.g. follow-on financing), (ii) provide a source of co-funding in the earlier stages of clinical development, and (iii) enable CIRM funded projects to access expertise within pharmaceutical and large biotechnology partners in the areas of discovery, preclinical, regulatory, clinical trial design and manufacturing process development.

"This initiative requires applicants to show evidence of either having 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; or (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.

"The objective of the first call under this initiative, the Strategic Partnership I Awards, is to achieve, in 4 years or less, the completion of a clinical trial under an Investigational New Drug (IND) application filed with the Food and Drug Administration (FDA)."

CIRM has scheduled a webinar on the RFA for prospective applicants for next Wednesday, April 25. It is asking for registration and questions in advance.



(Editor's note: An earlier version of this article did not contain the sentence about businesses receiving $54 million out of $1.3 billion awarded by CIRM.)

Source:
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International Stem Cell Corporation Updates on Marketing Strategy of Its Subsidiary Lifeline Skin Care

International Stem Cell Corporation (OTCBB:ISCO) http://www.internationalstemcell.com, a California-based biotechnology company focused on therapeutic and research products, announced today the selection of the Richards Partners as agency of record for its wholly owned subsidiary Lifeline Skin Care, Inc. ("Lifeline"). Lifeline offers luxury anti-aging skin care products based on its proprietary stem cell technology. Based in Dallas, the Richards Partners is the nation's largest independent branding agency.

Lifeline's skin care products were developed by a team of ISCO research scientists in collaboration with world-renowned cosmetic experts, and offer a comprehensive approach to skin care using patent pending moisture serums for day and night use. Made with human parthenogenetic stem cell extracts, the serums deliver anti-aging benefits, resulting in healthier and younger-looking skin. These products were launched in November 2010 and are available for purchase through the http://www.lifelineskincare.com website and selected luxury spas across the United States.

Adding Richards Partners to the Lifeline Skin CareTM team is part of Lifeline's plan to build on its initial successful product launch last year, and the Web based sales that have followed, by initiating a series of new marketing campaigns to further develop the Lifeline Skin CareTMbrand identity. These new marketing initiatives include traditional print and news media campaigns, as well as a new digital strategy focused on Internet and social media. "We are looking forward to working closely with the Richards Partners and leveraging their expertise in these areas to enhance the profile of Lifeline Skin CareTM and its revolutionary new skin care products," says Lifeline CEO Ruslan Semechkin, PhD. "Building a globally recognizable brand is a long-term process and this is an important step towards creating Lifeline's name. We believe this is a good time to begin these campaigns and continue our sales momentum resulting from our successful initial launch," Dr. Semechkin continued.

As previously announced the Mauldin Group, Lifeline's marketing partner, will be managing the day to day relationship with the Richards Partners and planning additional direct marketing initiatives similar to the successful initial launch in 2010. Tiffani Mauldin-Frederick, marketing partner of Lifeline Skin CareTM, says, "We're excited about working together with Richards Partners. We believe the collaboration will provide additional momentum and increase brand recognition for Lifeline Skin CareTM and help educate the public about the revolutionary science behind these products."

ABOUT INTERNATIONAL STEM CELL CORPORATION (ISCO.OB)

International Stem Cell Corporation is a California-based biotechnology company focused on the therapeutic applications of human parthenogenetic stem cells and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells with minimal immune rejection after transplantation into hundreds of millions of individuals of differing sexes, ages and racial groups. This offers the potential to create the first true stem cell bank, UniStemCell™, while avoiding the ethical issue of using fertilized eggs. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology and cell-based skin care products through its subsidiary Lifeline Skin Care. More information is available at ISCO's website, http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications please click on the following link:http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

FORWARD-LOOKING STATEMENTS

Statements pertaining to anticipated developments, product introduction plans and related support, the potential benefits of products, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products and the management of collaborations, regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update forward-looking statements.

Key Words: Stem cells, parthenogenesis, biotechnology, skin care, anti-aging

http://cts.businesswire.com/ct/CT?id=bwnews&sty=20110419005649r1&sid=14230&distro=ftp

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
1-760-940-6383
kaldrich@intlstemcell.com

or
Lifeline Skin Care, Inc.
Ruslan Semechkin, PhD, President & CEO
Vice President, ISCO
ras@intlstemcell.com

International Stem Cell Corporation Completes First Series of Pre-Clinical Testing of Hepatocytes Derived from Human Parthenogenetic Stem Cells

Data from successful animal study using liver cells derived from human parthenogenetic stem cells to be presented at two upcoming scientific conferences

Company also announces collaboration with Cedars-Sinai Medical Center for liver disease research, and completion of research on cytochrome P450 activity

International Stem Cell Corporation (OTCBB:ISCO) (ISCO) announces successful completion of the first series of preclinical testing of hepatocytes derived in the lab from human parthenogenetic stem cells (hpSC). In the transplantation mouse model, inoculated cells were capable of engrafting and surviving in specific niches within the liver, and were further developing into cells with essential hepatocyte-like features. Moreover, the transplanted cells could be identified in recipient tissue for a prolonged period of time.

The findings of these studies will be presented at the annual meeting of American Society of Gene & Cell Therapy, May 18-21 in Seattle, and at the International Society for Stem Cell Research annual conference, June 15-18 in Toronto.

"These results mark the achievement of a key milestone in our preclinical research," said Andrey Semechkin, Ph.D., ISCO's Chief Executive Officer. "Specifically, we have perfected the technique to transplant hepatocytes, an extremely fragile cell type, into the liver of animals, which is an easily injured organ. This preclinical research helps us develop our collaborations with clinics."

Nikolay Turovets, Ph.D., ISCO's Director of Research and Therapeutic Development commented "The next phase of research is to conduct experiments to demonstrate the ability of the transplanted cells to perform the vital functions of normal hepatocytes and, accordingly, their ability to modify disease by restoring the missing function of a patient's diseased liver."

The Company also announces the signing of a joint collaboration agreement with Cedars-Sinai Medical Center in Los Angeles to conduct research to develop therapies for liver diseases, in particular urea cycle disorders. Jeffrey Fair, MD., a liver transplant surgeon and Director of Translational Research for the Cedars-Sinai Comprehensive Transplant Center and Department of Surgery, will lead the Cedars-Sinai research team.

Dr. Fair said, "Urea cycle disorders are genetic deficiencies of liver function, which mostly affect newborns and oftentimes cause catastrophic neurological injury. It has been shown that transplantation of donor hepatocytes can save patient lives. Therefore, derivation of hepatocytes from hpSCs that can be immune-matched to the patient is a very pressing goal."

The Company also announces the completion of research focused on the investigation of cytochrome P450 activity and corresponding genes in hepatocytes derived from hpSC. According to the results, the differentiation technology developed by ISCO allows the creation of hepatocytes in the fetal stage of development. This research may contribute to the design of a product for future drug testing and discovery.

About International Stem Cell Corporation

International Stem Cell Corporation is focused on the therapeutic applications of human parthenogenetic stem cells and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in the creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells with minimal immune rejection after transplantation into hundreds of millions of individuals of differing genders, ages and racial background. This offers the potential to create the first true stem cell bank, UniStemCell™. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology, and cell-based skin care products through its subsidiary Lifeline Skin Care. More information is available at http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications, please click on the following link:http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

Forward-looking Statements

Statements pertaining to anticipated developments, research and development goals and related potential therapeutic treatments, the potential benefits of products, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products and the management of collaborations, regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update forward-looking statements.

http://cts.businesswire.com/ct/CT?id=bwnews&sty=20110426005697r1&sid=14230&distro=ftp

International Stem Cell Corporation
Kenneth C Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com

or
Nikolay Turovets, Ph.D.
Director, Research and Therapeutic Development
nturovets@intlstemcell.com

A Primer on the Use of Stem Cells in Ophthalmology by Irving J. Arons

An extremely comprehensive article about stem cell programs in opthalmology by Irving J. Arons

A Primer on the Use of Stem Cells in Ophthalmology
by Irving J. Arons

I recently came across an interesting news release from International Stem Cell Corporation (ISCO) announcing that it had formed a new business unit, Cytovis, to focus on stem cell programs in ophthalmology, including CytoCor for the cornea and CytoRet for the retina.

That got me thinking about how little I knew about what was going on in stem cell research in ophthalmology, despite having written about two developments in the field, the London Project to Cure Blindness and the University of California Irvine (UCI) program to develop an artificial retina based on stem cell research.

I decided to become better informed by taking a closer look at what was happening in this field, and presenting that story.

Introduction
Commenting on a EuroRetina Meeting held earlier in 2008, John Morrow of Newport Biotech Consultants noted, as reported by Ophthalmology Times Europe in September 2008, “Stem Cells are looked upon as either an ethical train wreck or the gateway to the alleviation of human illness, depending on which side of the political spectrum one resides. This unfortunate notoriety has resulted in unprecedented coverage in the media, but this has not done much to advance the cause of this technology. Yet recent ophthalmologic research suggests that the medical applications of stem cells hold notable promise for the treatment of ocular degenerative conditions and that realization of this potential may come about in the near future.”

I think Dr. Morrow’s thoughts eloquently sum up the subject. Stem cell research is politically charged but holds tremendous promise for the future, especially in ophthalmology.

What are Stem Cells?
Every organ and tissue in our bodies is made up of specialized cells that originally come from a pool of stem cells in the very early embryo (“embryonic stem cells”). Throughout our lives we rely to a much more limited degree on rare deposits of stem cells in certain areas of the body (“adult stem cells”) to regenerate organs and tissues that are injured or lost, such as our skin, our hair, our blood and the lining of our gut.

Stem cells are like a blank microchip that can be programmed to perform particular tasks. Under proper conditions, stem cells develop or “differentiate” into specialized cells that carry out a specific function, such as in the skin, muscle, liver, or in the eye. Additionally, stem cells can grow extensively without differentiating and give rise to more stem cells...

To read the full article, please visit - http://irvaronsjournal.blogspot.com/2010/09/primer-on-use-of-stem-cells-in.html

Kenneth Aldrich, Chairman and Co-Founder of International Stem Cell Corporation will be making two public appearances this week on behalf of ISCO.

On Monday, September 13, 2010, Mr. Aldrich will be speaking as part of a panel at the Stem Cells USA & Regenerative Medicine Congress in Philadelphia, discussing the topic, "Autologous vs. Allogeneic Business Models".
On Wednesday, September 15, 2010 at 9:35AM EDT, Mr. Aldrich will present at the Rodman and Renshaw Annual Global Investment Conference in New York. The webcast can be viewed live at: http://www.wsw.com/webcast/rrshq18/isco.ob. The presentation will be archived and viewable at the same link for 90 days. After the Rodman and Renshaw Conference, a link to the presentation will also be posted to the ISCO website, http://www.internationalstemcell.com.

Notes from The Chairman Concerning ISCO Price Fluctuations

As a matter of policy, we at ISCO refrain from commenting on movements in the price of our stock. However, events yesterday were so unusual and have resulted in so many questions, that I think it is our duty to our shareholders to tell you what we know.

As best we can determine, Patrick Cox, who has been and continues to be a strong supporter of our company, was required yesterday by his publisher to cease coverage of our stock and issue a sell recommendation because he has an equity interest in a company with which we do business that could have been perceived as a conflict of interest. That has resulted in numerous negative comments on investor message boards that referred to the sell recommendation without giving the background or a full explanation. As a result, I felt it was important that we put the day's events into proper context. The following are what I believe to be the relevant excerpts from Patrick's article:

As you know, I've been a huge promoter of International Stem Cell Corp.'s (OTCBB: ISCO) parthenogenic stem cell technology. I've not only told you about the company, but I appeared on John Mauldin's podcast show with ISCO board chairman Ken Aldrich about six months ago. Aldrich and Mauldin subsequently became friends and found that their organizations were a perfect fit for marketing ISCO's cosmeceutical skin care product.

John Mauldin asked me to be a part of that organization. We looked hard at Agora Financial's policies as well as applicable SEC regulations and concluded that there would be no conflict of interest because the position gave me no direct interest in ISCO or its stock price....

My publisher, however, has grown increasingly uncomfortable with this arrangement. The reason is not that Agora Financial believes that there would be an actual conflict of interest. Rather, it is that it might be perceived as one by some, in particular SEC lawyers....

My publisher's trading policy's aim, however, is to keep me purely objective and disinterested. This policy is debatable, but I respect it. My only option, therefore, is to issue a sell order or face the wrath of a disappointed spouse.

You can probably guess what that means. I'm going to have to issue a sell order.

Patrick followed that with a supplement, in which he said, in part,

Just to re-iterate, now that I've seen the price action from this afternoon's sell alert, I'm not parting with the shares of International Stem Cell Corp. (OTCBB: ISCO) because I believe they are a bad investment (my feelings, as you probably know, are quite the opposite)...ISCO still has the transformational potential that I've told you about. The only real change is that I won't be able to update you from here on out -- due to an over abundance of caution from my publisher.

Obviously, we can't know for certain if these articles caused the price movement yesterday, but we believe they were a major factor. Moreover, the comments and the response of investors to them are beyond our control, but we do want to reassure all interested parties that there is no information of which we are aware to justify the price fluctuation that occurred yesterday.

I hope this will prove helpful.

Sincerely,

Ken Aldrich

Chairman

FORWARD-LOOKING STATEMENTS:

Statements pertaining to anticipated developments, the potential benefits of collaborations, affiliations, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products and the management of collaborations, regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update forward-looking statements.

More about salinomycin

New mission for salinomycin in cancer by Cord Naujokat, SciTopics, July 15, 2010. Excerpt (in the "continue reading" section):

In addition, a very recent study demonstrates that salinomycin overcomes ATP-binding cassette (ABC) transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like cells (3).

Reference #3: Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells, by Dominik Fuchs and 4 co-authors, including Cord Naujokat, Biochem Biophys Res Commun 2010(Apr 16);394(4): 1098-104 [Epub 2010(Mar 27)][PubMed citation].

Comments: Near the end of this article about salinomycin is the comment that "the investigation of its safety, toxicity, pharmacology and anticancer activity in humans will be a challenge." The author then mentions a preliminary study of "a small cohort of patients with metastatic breast cancer or metastatic head and neck cancers". The results of this preliminary study of the toxicity of salinomycin are summarized. They have not yet been published in the peer-reviewed literature, although a manuscript has been submitted [see reference #4 in the article]. The implication of these preliminary results is that there may be a "therapeutic window" for salinomycin, that is, a drug dosage that yields clinically significant benefits in the absence of excessive toxicity.

For a previous commentary on salinomycin, see: Cancer stem cell breakthrough by Kat Arney, Science Update blog, Cancer Research UK, August 14, 2009. Excerpt:

We need to stress that these were laboratory experiments, and there is no evidence yet that salinomycin can treat cancer in humans. Salinomycin is currently used as an antibiotic for chickens and cows, and it can be toxic or even fatal to humans, causing serious muscle and heart problems.

If there is a "therapeutic window" for salinomycin, it could be a small one, and is likely to vary from one tumor to another.

For a previous post to this blog about salinomycin, see: Identification of selective inhibitors of breast CSCs in mice, August 14, 2009.

Disagreement about melanoma CSCs

The Evolving Science of Cancer Stem Cells by Carmen Phillips, NCI Cancer Bulletin 2010(Jul 27); 7(15). Excerpt:

Researchers from Stanford University earlier this month reported in Nature that they had found a marker, CD271, that identified a somewhat unique population of cells that could produce melanoma in highly immunocompromised mice; anywhere from 2.5 percent to 41 percent of cells in their human tumor samples expressed the marker. In additional experiments using similar mice on which human skin was engrafted, only tumor cells with the marker could produce tumors and metastases in the mice. (In his lab, Dr. Morrison noted, the same marker did not differentiate tumor-forming from nontumor-forming cells.)

The publication about CD271 is: Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 by Alexander D Boiko and 11 colleagues, Nature 2010(Jul 1); 466(7302): 133-7. [PubMed citation].

Comments: The sentence: "In his lab, Dr. Morrison noted, the same marker did not differentiate tumor-forming from nontumor-forming cells" is noteworthy. Why the difference in results for CD271?

The publication by Boiko and co-authors was cited in a previous post to this blog, "Melanoma-initiating cells identified", dated July 1, 2010.

See also an earlier post to this blog, "Tumorigenic cells not rare in human melanoma", dated December 3, 2008.

International Stem Cell Corporation Engages Leading Immunogeneticists to Advance its Industry-first, Immune-matched Stem Cells

International Stem Cell Corporation (OTCBB:ISCO), http://www.intlstemcell.com, today added two world-leading immunogeneticists to its scientific advisory board. They and ISCO scientists will study the immune-matching properties of ISCO's human parthenogenetic stem cell (hpSC) technology and the potential for each hpSC-derived therapeutic cell to be an immune-match for millions of people.

Dr. Hans-Dieter Volk, Professor of Immunology and Chair of the Institute of Medical Immunology and Berlin-Brandenburg Center for Regenerative Therapies (BCRT) at Charité Universitätsmedizin in Berlin, and Dr. Matthias von Herrath, Professor at the La Jolla Institute of Allergy and Immunology at University of San Diego, have agreed to join ISCO's scientific advisory board. Both have dedicated their careers to experimental and clinical immunology and are highly regarded immunogenetics experts internationally. They will be most valuable as ISCO attempts to demonstrate the unique immune-matching benefits of the hpSC technology experimentally and in clinical practice.

"We believe that providing human cells that can minimize rejection though immune-matching to the recipient is one of the most important tasks in developing effective regenerative medicine therapies," says Dr. Simon Craw, Vice President at ISCO. "We look forward to Drs. Volk and von Herrath helping us try to demonstrate how that need can be met with our parthenogenetic stem cells."

Embryonic stem cells (hESC) almost invariably have different forms of genes (called "alleles") at each genetic position of the paternal and maternal chromosomes, i.e. they are "heterozygous." This includes the human leukocyte antigen ("HLA") genes that are largely responsible for the distinction between "self" and "foreign," and thus acceptance or rejection of transplants. Since hESC are derived from fertilized embryos, they carry the genes of a unique individual, thus the therapeutic cells derived from hESC will carry HLA alleles that can be recognized as foreign and be rejected by most patients unless they receive immunosuppressive therapy. Such therapy is costly, has significant side effects, and often is disabling in the long term.

Like most individuals in the population, induced pluripotent stem cells ("iPS" cells) and adult stem cells are also predominantly heterozygous because they carry paternal and maternal chromosomes. They are a perfect immune match to the patient they came from and are therefore typically administered back to that same individual ("autologous therapy"). However, they would likely be rejected by most other recipients. Autologous therapy is time-consuming and expensive, which goes against the cost containment pressures globally. In addition, the quality of the therapy is directly related to the ability to secure clinically sufficient numbers of functional cells from the patient, which often poses a significant problem in clinical practice.

In contrast, the hpSCs developed by ISCO are derived from unfertilized eggs ("oocytes") that have been shown in peer-reviewed journals to exhibit unlimited proliferation potential and are pluripotent (can become cells from all three germ layers that form a human being). Most significantly, hpSC can be created in a "homozygous" state, where the alleles, including the HLA alleles, are the same at each genetic position. When these HLA alleles are also found with a high frequency in a population, these "HLA-homozygous" stem cells and their therapeutic derivatives have the potential to be immune matched to millions of people. For example, ISCO's first homozygous stem cell line with high-frequency HLA alleles has the potential to be immune matched to an estimated 75 million people worldwide.

Dr. Volk says: "Using my experience from transplantation immunology and medicine during the past three decades, I am very pleased to help ISCO in their efforts to make its hpSC technology a clinical reality where therapeutic cell derivatives will be immune matches for millions of people worldwide." Dr. von Herrath continues: "While stem cell technologies generally offer great regenerative potential, most clinical applications will be limited by immune rejection. I look much forward to joining ISCO in their quest for making stem cell-derived therapy a practical and attractive clinical option for many degenerative diseases."

Besides the immunogenetic developments, ISCO is advancing its hpSC technology into the differentiation of hpSC into therapeutic cells and tissues and into the establishment of processes and facilities to produce clinical-grade cells. The company is seeking to demonstrate the therapeutic potential of its hpSC technology as a safe, efficient, and superior alternative to other sources of stem cells for human therapy.

ABOUT INTERNATIONAL STEM CELL CORPORATION (ISCO.OB):

International Stem Cell Corporation is a California-based biotechnology company focused on therapeutic and research products. ISCO's core technology, parthenogenesis, results in creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells with minimal immune rejection after transplantation into hundreds of millions of individuals of differing sexes, ages and racial groups. This offers the potential to create the first true stem cell bank, UniStemCell™, while avoiding the ethical issue of using fertilized eggs. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology. More information is available at ISCO's website, http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

FORWARD-LOOKING STATEMENTS

Statements pertaining to anticipated technological developments and therapeutic applications, and other opportunities for the company and its subsidiary, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "should," "believes," "plans," "anticipates," "expects," "estimates") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update these forward-looking statements.

Key Words: Stem Cells, Biotechnology, Parthenogenesis

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
or
Brian Lundstrom, President
760-640-6383
bl@intlstemcell.com

Sessions on CSC Therapeutics at AACR10

There were two poster sessions on Cancer Stem Cell Therapeutics at the 101st Annual Meeting of the American Association for Cancer Research (AACR). The sessions, Cancer Stem Cell Therapeutics 1 and Cancer Stem Cell Therapeutics 2, took place on the morning and afternoon of April 20, 2010 [FriendFeed entry].

Two posters presented in the 2nd session have been highlighted in a news release. See: Alchemia’s HyACT Technology Enhances the Killing of Cancer Stem Cell Populations in Breast and Colorectal Cancer, Business Wire, April 20, 2010 [FriendFeed entry]. One of these is Poster #4293: Evaluation of activated CD44 as a biological target in the eradication of breast cancer stem cells, by Vera J Evtimov and Tracey J Brown [Presentation Abstract]. The other is Poster #4278: HA-Irinotecan targeting of activated CD44 is an effective therapy for the eradication of putative colon cancer stem cells [Presentation Abstract].

CSC news links 2010-05-08

For links to recent news items about CSC, visit this [Topsy] page. Examples of two news items that have received attention in the past week:?

New research links ovarian hormones with breast stem-cell growth - Globe and Mail http://bit.ly/brT71E. Hashtag: #cancerSC. Posted to Twitter on Wed May 06, 2010 via TweetDeck. [PubMed Citation]


Broccoli compound limits breast cancer (about sulforaphane) http://bit.ly/9blnNP & http://bit.ly/aOTSDv. Hashtag: #cancerSC. Posted to Twitter on Wed May 05, 2010 via TweetDeck. [PubMed Citation]

Irradiating brain's stem cell niche

Irradiating brain's stem cell niche doubles survival time for patients with brain cancers by Kim Irwin, News Release, UCLA Newsroom, July 23, 2010. Excerpt:

Patients with deadly glioblastomas who received high doses of radiation that hit a portion of the brain which harbors neural stem cells had double the progression-free survival time as patients who had lower doses or no radiation targeting the area, a study from the radiation oncology department at UCLA's Jonsson Comprehensive Cancer Center has found.

The news release is based on this OA publication: Irradiation of the Potential Cancer Stem Cell Niches in the Adult Brain Improves Progression-free Survival of Patients with Malignant Glioma by Patrick Evers and 6 co-authors, including Frank Pajonk, BMC Cancer 2010(Jul 21); 10(1):384. [Epub ahead of print][FriendFeed entry].

Comment: On the brain as a model system to study the impact of radiation dose given to stem cell niches. Provides clinical evidence, based on an improvement in progression-free survival, to support the hypothesis that higher radiation doses to neural stem cell (NSC) niches improves patient survival by eradicating CSCs.

Critical molecular pathways in CSCs of CML

Critical molecular pathways in cancer stem cells of chronic myeloid leukemia by Y Chen, C Peng, C Sullivan, D Li and S Li, Leukemia 2010(Sep); 24(9): 1545-54. Epub 2010 Jun 24. [Connotea bookmark][PubMed citation][Full text]. The abstract of this OA review:

Inhibition of BCR-ABL with kinase inhibitors in the treatment of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML) is highly effective in controlling but not curing the disease. This is largely due to the inability of these kinase inhibitors to kill leukemia stem cells (LSCs) responsible for disease relapse. This stem cell resistance is not associated with the BCR-ABL kinase domain mutations resistant to kinase inhibitors. Development of curative therapies for CML requires the identification of crucial molecular pathways responsible for the survival and self-renewal of LSCs. In this review, we will discuss our current understanding of these crucial molecular pathways in LSCs and the available therapeutic strategies for targeting these stem cells in CML.

Painful Decisions Coming Up at Stem Cell Agency


The
Sacramento Bee
today ran a piece by yours truly in its California
Forum
section.

Here
is an excerpt. You can find the entire article here.

"They're
talking about pain at the $3 billion 
California stem
cell agency. And mortality. But not the end of life as you and I know
it.

"They're
talking about the pain that comes from cutting off millions of
dollars for scientists. They're talking about what will happen when
the state stops borrowing money to finance 
stem
cell research
 –
a final-breath moment that arrives in about five years....

"CIRM's
changing priorities create 'stark tension,' said one board
member, Michael Friedman, CEO of the City of Hope in the Los Angeles
area, in January. 'We're going to have to make some really
painful and difficult decisions,' he told directors.

"CIRM's
success – or lack of it – will play a critical role in its future
finances, whether they are based on another bond measure or private
support."

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Stem Cell Agency Hires Tech Chief to Solve a Myriad of Problems


In a move that was long overdue, the $3
billion California stem cell agency last week hired a director of
information technology to straighten out key problems ranging from
its grants management system to how it handles its website.

The new hire comes as the CIRM
governing board faces the results of its first-ever performance audit, which is markedly critical of how the agency handles its
information. Half of the audit's 20 highest priority recommendations for improvement focus on information deficiencies, including
critical information necessary for CIRM executives to determine the
agency's performance.
Solving those problems will fall on
the shoulders of Bill Gimbel, who is no stranger to CIRM. He has been
working with the agency as an information technology advisor since
2010 through a contract with Infonetica, Inc., of Pleasanton, Ca., according to CIRM spokesman Kevin McCormack.  Gimbel is now the first staff person in a chief technology position at CIRM since October 2007, when about 25 percent of CIRM employees left.
Bill Gimbel
A graduate of MIT, Gimbel, who will be
paid $180,000 annually, has a broad range of experience in computer
technology and software dating back to 1992. According to his
Linkedin web site, he was most recently director of IT at Infonetica.
He lists himself as owner of aptReader, an app for reference books.
He has also worked for LearningExpress and Scholastic, Inc.
The stem cell agency has been wrestling with information technology issues for years. The critical grants
management system has been an issue at least since 2007, when
directors were told its costs would not exceed $757,000. No figures
for the total spent since then have been made public by CIRM, which
is attempting to build a custom system, but the amount clearly and
easily surpasses the 2007 estimate, based on some of the outside
consulting costs. Although the agency hopes to resolve many of the
problems by the end of this calendar year, the grant system was the
target of considerable attention by Moss Adams, the firm that
prepared the performance audit.
Over the years, CIRM directors have received
intermittent, sketchy CIRM staff reports about the grants management
system, but the Moss Adams discussion is the most
comprehensive.
Among other things, the Moss Adams report said in bureaucratically delicate language,

 "Integration
of website content management has not been an integral part of the
GMS (grants management system) development process, which could
result in suboptimal operational efficiency and effectiveness.

"Grants management system
development is effectively managed at a tactical level, but it lacks
dedicated, strategic governance and oversight, which has resulted in
an elongated development process and requirements conflicts."

Moss Adams said,

"The new grants management system
intellectual property module, currently under development, does not
include provisions to address commercialization activity."

The performance audit additionally
said,

"CIRM board members and senior
management do not receive regularly updated, enterprise-level
performance information. The ability to evaluate performance against
strategic goals is critical to effective leadership and program
monitoring, evaluation, and reporting. CIRM does not currently have a
formal performance reporting program."

Moss Adams continued on other
information technology topics:

"Data and document access are
inefficient as a result of CIRM operating without a document
management system.....In most cases, CIRM staff cannot access
information without human interface. Information is stored in
multiple locations, which are not linked or indexed."

The audit said that the agency has
tried to solve its information problems without a plan. 

 "CIRM’s
information system needs have been met by a variety of tools,
including in-house developed applications, off-the-shelf
applications, databases, and spreadsheets, most of which are not
integrated," the audit stated.

One of the effects of all this is much
wasted time when CIRM's tiny staff tries to extract information from
the hodge-podge of systems. It is time that cannot be spared as the
workload increases in the next few years, as it is certain to do. 
CIRM's 29-member board is scheduled to consider the performance audit at its meeting this Thursday. 

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss