Correction

A June 30 item involving the Alpha clinic program incorrectly stated that the program involved $34 million. The correct figure is $24 million.

Three Top Execs Named Today at $3 Billion California Stem Cell Agency

The California stem cell agency today marked the completion of a year-long reorganization with the appointment of three top executives, including a veteran of Genentech.

Randy Mills, who became president of the $3 billion agency in May 2014, said the appointments represent a “significant inflection point.”

Mills said in a press release,

“People are everything when it comes to the potential and performance of an organization.  With the appointment of these three exceptionally talented individuals to the leadership team, CIRM is now better positioned to achieve its mission and forever change the practice of medicine.”

The trio consists of Ramona Doyle, vice president of therapeutics; Maria Millan, senior director of medical affairs and stem cell centers, and Maria Bonneville, director of administration. Millan and Bonneville both were promoted from within the organization.

Ramona Doyle, Rhodes Project photo

Doyle comes from Genentech. She was senior group medical director for respiratory product development at the South San Francisco business, where she has worked since 2009. She worked for Gilead Sciences for two years. Doyle has also taught at UC San Francisco and at the Stanford Medical School, where she worked with Millan.

Beginning Monday, Doyle will oversee projects involving neurological and ocular, cancer and blood related and cardiovascular, lung, liver and other organ system-related conditions. She is also the only person designated as vice president within the agency, formally known as the California Institute for Regenerative Medicine (CIRM).

Doyle received her M.D. from Emory University and was a Rhodes Scholar after receiving an undergraduate degree in English and literature from Sewanee: The University of the South. When she was at Sewanee, she was editor of the Mountain Goat literary magazine and wrote prize-winning poetry.

Also named today as senior director of medical affairs was Maria Millan, who formerly was a

Maria Millan

medical officer at CIRM, which she joined in 2012. Prior to that, she was vice president and chief medical officer at StemCells, Inc., and director of the pediatric liver and kidney transplant program at Stanford, where was also an associate professor. Millan, a surgeon, is overseeing the agency's $34 million Alpha stem cell clinic program. 

Prior to Bonneville's appointment today as director of administration, she was executive director of the CIRM board. She will have oversight over the agency’s board relation, human resources, communications and information technology departments. Before joining CIRM, she was a consultant with Tramultola LLC and worked for former state Treasurer Bill Lockyer as finance director for Northern California.

Other members of the agency’s “leadership team” are Chila Silva-Martin, finance director, Gil Sambrano, director of review; James Harrison, general counsel; Gabe Thompson, director of grants management, and Patricia Olson, executive director of discovery(basic research).

All have been with the agency for some time. Harrison is an outside contractor.

Not including Mills, the 8-member leadership team at CIRM now consists of five women and three men. 

California's Stem Cell Program, Brain Cancer and the City of Hope

The City of Hope said yesterday that it has treated the first brain tumor patient at its state-financed Alpha stem cell clinic, part of an ambitious program aimed at creating four one-stop stem cell treatment centers in California.

The City of Hope announced that the unidentified patient was involved in a clinical trial using genetically modified neural stem cells to help deliver chemotherapy to brain cancer cells.

The press release said,

“The aim of this neural stem cell research is to develop a treatment that is more potent and less toxic than existing treatments for brain tumors.” 

 The Alpha Clinic program was created last October by the $3 billion California stem cell agency. It awarded $24 million for clinics involving UCLA, UC San Diego and UC Irvine in addition to the City of Hope, which is located in Duarte in the Los Angeles area.

Karen Aboody, co-leader of the Developmental Cancer Therapeutics Program at City of Hope, said,

Karen Aboody, City of Hope photo

  “Rather than putting chemotherapy through the whole body and possibly causing significant side effects that affect quality of life, the neural stem cells produce active chemotherapy only at the sites of the tumor, killing surrounding cancer cells.”

Maria Millan, who oversees the Alpha program for the stem cell agency, said,

 “This work does more than help just one person. Because they are part of the Alpha Clinics Network, City of Hope is demonstrating how by working together, providing collective expertise, efficiencies and critical resources, we can help accelerate the development of stem cell treatments for patients with unmet medical needs.”

 The City of Hope study now has several patients and is looking for more.­­­­­

Today is the Last Day to Weigh in on the Direction of the California Stem Cell Agency

Don't like what the California stem cell agency is doing? Want more clinical trials and less basic research? Do you think the agency is too cozy with business or not cozy enough?

Here is your chance to tell the agency directly what it should do. But today is the last day that you can participate in the survey of the public -- that includes researchers -- concerning the direction of the state's $3 billion enterprise.

The agency has mounted an online questionnaire that can be completed anonymously. It has 13 questions -- possibly the agency's lucky number -- with plenty of space to add comments.

The survey is part of the agency's revision of its plan for spending its remaining $800 million over the next few years.

"No one has a monopoly on good ideas," said Randy Mills, president of the agency, in soliciting comments from every quarter. Mills is expected to bring his latest thinking on changes in the agency's strategic plan to its governing board in late July.

The California Stem Cell Agency Celebrates a First

The California stem cell agency today marked a signal event in its most advanced clinical trial by declaring: 

“Some things never get old. Like watching the sunset over the Grand Canyon. Listening to a baby laugh. Watching the San Francisco Giants win the baseball World Series. Now you can add to that list learning that one of the clinical trials we are funding has just treated their first patient.”

­­­­­­­­

The piece by Kevin McCormack, senior communications director for the agency, referred to Caladrius Biosciences, Inc., which in May was awarded nearly $18 million by the agency. (Caladrius was formerly known as NeoStem.)

The money is going into a phase three trial for a treatment of metastatic cancer, the most lethal form of skin cancer. It is the first phase three trial in which the agency has participated.

McCormack wrote,

“Caladrius’ approach is a personalized one. They use the patient’s own tumor cells to create a therapeutic vaccine called (for now at least) CLBS20. It’s designed to engage the patient’s own immune system and destroy the cancer.

“This first patient was treated at Thomas Jefferson University Hospital in Philadelphia. Altogether Caladrius hopes to enroll some 250 patients at more than 40 sites worldwide, for the trial. Seven of those sites are here in California; that’s the portion of the project we are funding.”

Caladrius, which is headquartered in New York City, also issued a press release in which David Mazzo, CEO of the firm, described the enrollment of the first patient as a “milestone.”

Caladrius recently announced that it had “entered into a material transfer agreement with the University of Southern California and the California Institute of Technology, concerning next-generation strategies for its core cancer technology.”

The company’s stock today closed at $2.00, down 3.85 percent. Its 52 week low is $1.82. The 52-week high is $7.22.

The California Stem Cell Agency Wants Help in Charting New Directions

How to spend $800 million?

Friday deadline for comments

Want to tell the $3 billion California stem cell agency where to go? Here’s your chance.

The agency said today it wants to hear from you. It is open to suggestions, rude and otherwise. But it really wants to hear constructive comments and critiques.

“No one has a monopoly on good ideas,” said Randy Mills, president of the agency, in a statement that unveiled the enterprise’s most recent effort to elicit proposals and thoughts from the public.

What this is all about is revision of the agency’s strategic plan, which is an indirect way of asking the question of “how are we going to spend our last $800 million.”

The agency has mounted an online questionnaire with plenty of room for comments beyond the formal structure of the survey. Thirteen questions are posed. They include such matters as how much risk the agency should take and just how it should be measured. The agency wants to know whether the top three measurements should include such things as the number of scientific articles published or the number of patients treated. It wants to know whether you think the agency is sufficiently focused on its mission.

Time is short for persons who want to weigh in on the survey, which is designed to be answered anonymously. It must be completed by this Friday.

Jonathan Thomas, chairman of the agency board, noted that the effort is part of the agency’s responsibility to the public. He said,  

“We are a state agency. We were created by the people of California, and we answer to the people of California.”

 Mills said,

“That’s why we want to hear from a diverse group of people, scientists and non-scientists alike, to learn what they think about how we should best use our money, resources, and expertise to reach our goal. This new strategic plan will help create a clear vision for how we move forward, one that sets priorities and an actionable approach to accomplish our mission.” 

At the end of July the board is scheduled to hear what Mills has prepared up to that point on the strategic plan for the next five years or so, which is about how long the agency's current funding will last. 

The Hard Business of Stem Cell Economics and Patient Needs

Premature clinical trial shutdown?

Implications for California stem cell agency

The vagaries of Big Pharma and development of stem cell therapies -- plus the frustrations of a prominent Stanford researcher -- were the topic this week in a major California newspaper.

Irv Weissman, Stanford photo

The researcher is Irv Weissman, head of the stem cell program at the Palo Alto university. The companies are Sandoz Pharma, Ciba-Geigy and Novartis. The story also includes a $392 million deal involving Weissman.

The basic storyline, as reported June 14 by Lisa Krieger of the San Jose Mercury News, is that years ago Weissman developed a “unique way to grow and deliver blood stem cells to desperate patients with aggressive cancers, boosting survival rates.”

According to Krieger, Weissman in effect sold the potential stem cell therapy to Sandoz in 1991 for $392 million in an effort to place “his innovation into the hands of a company large and prosperous enough to accelerate research.”

Sandoz then “merged with Ciba-Geigy and became Novartis, which bought the remainder of Weissman's company (Systemix) for $76 million in 1997 -- and, with it, all patents,” according to Krieger.

Novartis shut down the trials in 2000 along with Weissman’s company. Krieger reported that the firm “ended the program because it couldn't produce blood stem cells in large enough numbers to develop a commercial market -- and it was not in the business of producing personalized ‘custom-made’ therapies.”

Krieger continued,

Karuna Jaggar, BCA photo

"'Well before the launch of the War on Cancer, the corporate profit motive has driven the cancer research agenda,' said Karuna Jaggar, executive director of the Breast Cancer Action, a San Francisco-based patient advocacy group. 'Time and again, history has shown that it is not only the possibility of saving lives but the potential of making money that has steered the research agenda toward some areas -- and away from others.

"'As long we have a health care system that puts profits before patients we will always be at the mercy of corporations looking to make profits. Any new innovation needs to be evidence-based and proven safe and effective no matter what money is to or is not to be made,' she said.”

Krieger wrote,

“Now, a quarter-century after it was conceived, the technique is finally back in Weissman's hands at Stanford -- although Novartis still holds the patent.” 

She reported that Weissman hopes to take the potential therapy forward in a non-profit setting.

Krieger has much more in her story, which offers considerable food for thought, particularly in connection with California’s $3 billion effort to bring a stem cell therapy into widespread use. It has not done so yet after nearly 11 years of trying and the expenditure of roughly $1.9 billion.  The agency also suffered a significant blow at the hands of one company, Geron, that dropped -- for financial reasons -- the first-ever clinical trial  for a hESC stem cell therapy, which the agency had backed with a $25 millon loan. 

The agency is currently revising its strategic plan. Randy Mills, president of the agency, says he is serious about developing a solid plan that will be followed assiduously with measurable benchmarks along the way.  

Our view: One important element in the new plan should focus on avoiding situations such as those involving Geron (see here and here) and the morass that Weissman fell into.

Whether one likes it or not, the facts of life in the biomedical world – pleasant or unpleasant – mean that business must be firmly engaged if a stem cell therapy is to be widely available to the public. Government agencies, however, often fall short in their dealings with private firms. For the stem cell agency, that means it needs a keen eye and clear goals when it deals with Big Pharma and stem cell firms. And if the California’s stem cell agency is to deliver on the promises made to the people of California, it must be willing to walk away from a deal if the terms aren’t right.

California Hits Its Mark on Faster Delivery of Cash for Stem Cell Research

• Caladrius to get first installment on nearly $18 million 
• Agency President Randy Mills Pleased with CIRM 2.0 Overhaul

 SAN FRANCISCO -- The California stem cell agency may not be faster than a speeding bullet, but it is running way more quickly than it was a year ago.

For researchers and patients, that means the agency’s millions are moving more rapidly into development of therapies and cures with the goal of beginning to save lives sooner rather than later.

The signal event came last week when the agency, formally known as the California Institute for Regenerative Medicine(CIRM), signed off on a contract with Caladrius Biosciences, Inc., of New York.

As soon as Caladrius signs the agreement, it will receive a check for $3 million, the first installment on a nearly $18 million award that was approved by directors less than a month ago. 

Randy Mills

CIRM President Randy Mills was delighted last Friday when he told the California Stem Cell Report about the action on the Caladrius award. (Caladrius was formerly known as NeoStem.)

Mills, who has been head of the agency for only a little over a year, mentioned the news during a 45-minute conversation in his office at CIRM headquarters.

It was the first award paid out under Mills’ new, CIRM 2.0 program, an effort designed to speed cash to researchers and improve the quality of applications. It is also the first CIRM award in a stage three trial, the last step in the process of winning government approval for widespread public use of a therapy.

The agency approved the actual Caladrius contract last Thursday, 21 days after the directors’ approval. Mills’ goal was to act on the contract within 45 days.

CIRM’s 2.0 clock shows Caladrius’ application for the melanoma therapy coming in at the end of February, 113 days ago. Mills’ goal is to have action completed on an application within 120 days from the time it officially enters the 2.0 system -- instead of up to two years as in the past. 

The firm offered its initial application at the end of January, but it was sent back for improvement. 

Next up in the first round of CIRM 2.0 awards is final action on a $5 million award to Shaomei Wang of Cedars-Sinai that was also approved on May 21 by CIRM directors.

Mills said last Friday that CIRM 2.0 has not been perfect and that in some cases implementation required "brute force." But he is pleased overall. Later this year, Mills and his team plan to apply CIRM 2.0 to basic and translational awards, all of which will mean significant changes for hundreds of California scientists. 

California Stem Cell Agency Symposium: 'Vague Fears' vs. Potential Genetic Alteration of Human Race

California’s $3 billion stem cell agency has called a high-level meeting for next fall to examine a
"red-hot" issue that many prominent researchers say could lead ultimately to alteration of the human race.

The topic is a technique that makes it much easier to alter the genetic make-up of individuals in a way that can be inherited by their offspring.

In April, scientists in China reported genetically modifying human embryos in what was regarded as a “world first.” (See here and here.)

That came after a group of leading scientists in March called for a global moratorium on the genome-editing practice, stating that the therapeutic benefits were tenuous.

More recently Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, wrote on May 28 about how the subject was viewed at a meeting called, “Biotech and the Ethical Imagination: A Global Summit.”

Steven Pinker

“The far end of techno-enthusiastic perspectives, both on human germline modification specifically and on biotech in general, was represented by Harvard experimental psychologist and popular science writer Steven Pinker. In his opening remarks, Pinker counseled bioethicists to ‘stay out of the way of progress.’ In his closing comments, he cast ‘vague fears’ as standing in the way of saving millions of lives. In between, he epitomized the ‘bad boy scientism’ that too frequently characterizes the biotech field.” 

Jonathan Thomas, chairman of the stem cell agency, and Geoff Lomax, the agency’s main person on bioethics, wrote on June 1 about the matter and the upcoming meeting. In an item on the agency’s Stem Cellar blog, they said,

“Given CIRM’s support for research activities where genome editing may be employed, we believe it is important to have effective policies to guide our future funding decisions. Therefore, we have charged the CIRM Medical and Ethical Standards Working Group with convening a public workshop to elucidate the scientific and policy considerations surrounding genome editing in the context of CIRM supported research. This workshop is a first step in evaluating whether CIRM should make changes to its existing policies governing stem cell research.”

 CIRM’s standards group consists of some of the top bioethicists in the country. Early on, they developed the agency’s rules for research on stem cells, which were the most advanced in the country at the time. The chairman of the group is Bernie Lo of UC San Francisco.

The genome-editing issue to be discussed in November was originally scheduled to be brought up at an April meeting of the standards group. However, it was put off for a variety of reasons. Thomas subsequently called the meeting for next fall.

At the April meeting, Ted Peters of the Pacific Lutheran Theological Seminary and a member of the stem cell standards group, said the issue was “red hot.”  Jeff Sheehy, a member of the agency board and a communications manager at UC San Francisco, said the agency needed to clarify where it stood.  

Robert Taylor of the Emory School of Medicine and also a member of the standards group, said,

“There are companies that are offering to do this for your cell line, so it's really out there.”

Lo said,

“I think Jeff has raised a really important, complex and breaking topic. I think the idea of having a symposium to deal with both the science, and the ethics policy could be a really important thing to do.” 

 Suggestions regarding the meeting can be sent to Lomax at glomax@cirm.ca.gov. 

NeoStem's New Name, Backed by $29 Million in New Cash

The caladrius at work

Say hello to the latest recipient of nearly $18 million from the California stem cell agency -- Caladrius Biosciences, Inc.

It is also a firm that is $29 million richer -- on top of the $18 million -- than it was when the $3 billion state research enterprise awarded the firm the money on May 21.

Caladrius is the new name for NeoStem, Inc., of New York, N.Y.  It is also the name of a video game once described by the Giantbomb web site as a “A 2013 bullet hell shooter from Moss.”

Caladrius has a longer history, however, than the video game. According to The Medieval Bestiary web site, the caladrius is an all-white bird – sort of a mythological diagnostic tool – that would refuse to look into the face of patients who were going to die. But the caladrius could also draw out the disease from the sick person and fly away with it.

David Mazzo, president of the firm, said yesterday,

“With the same objective of patient recovery, we, now as Caladrius Biosciences, are committed to bringing significant life-improving therapies to market, driving the evolution of the cell therapy industry and generating industry-leading growth through our innovation and executional excellence.” 

Caladrius sold more than 14 million shares of its stock earlier this month, raising nearly $29 million to help pay for the third stage clinical trial that has been backed by the stem cell agency. The firm is using the proceeds for, among other things, to meet the required match of the California state funding. The four-year trial is aimed at metastatic skin cancer. 

In his letter to shareholders yesterday, Mazzo laid out the future direction of the firm. He also cited the acquisition of an “asset” a year ago that provided the therapy now being funded by California. Mazzo said,

“Given that we acquired this asset approximately one year ago and, in the ensuing months, much of the external focus on our company was on our ischemic repair Phase 2 program, we believe that the market has not yet integrated the full potential of this mature immuno-therapy asset into the value of our company.”

Mazzo referred to the $124 million acquisition of California Stem Cell, Inc., of Irvine, Ca. Hans Keirstead, the president of that firm, is now senior vice president, research, and chief science officer of Caladrius.

Caladrius’ stock closed at $2.21 a share today, down from $2.30 on May 20, the day before it was awarded the California money. The stock has ranged from $2.03 to $7.23 over the last 52 weeks, but it jumped dramatically the day following the award and then fell back.

The Caladrius video game figure is markedly different than the bird depicted by medievalists(see below). For a review of the game, see here.  

Caladrius Blaze, the video game figure

NeoStem Stock Price Falls 22 Percent as It Seeks to Match California Stem Cell Grant

NeoStem, Inc., has had a wild financial ride this past week with its stock price soaring and then plummeting in the wake of a nearly $18 million award last Thursday from the California stem cell agency.

The share price of the New York firm dropped 22 percent today after it announced that it was seeking to raise $25 million by selling 12.5 million shares. The move is aimed at helping to finance its stage three melanoma trial. Terms of the California award require a dollar-for-dollar match of the agency’s funds for the trial.

The market was not happy with the company’s plans to sell more of its stock at a possible price of $2.00 share. The stock today closed at $2.06. Last Thursday it closed at $2.95, up 28 percent for the day. Its 52-week performance has ranged from a low of $2.03 to a high of $7.23.

The Street web site today was critical of the firm, giving its stock a D-minus rating and recommended selling it.  The Street said,

“This is driven by a number of negative factors, which we believe should have a greater impact than any strengths, and could make it more difficult for investors to achieve positive results compared to most of the stocks we cover. The company's weaknesses can be seen in multiple areas, such as its deteriorating net income and generally disappointing historical performance in the stock itself."

Last week, some stem cell agency board members raised questions about the financing of the trial. Steve Juelsgaard, former executive vice president of Genentech, asked about the company’s “plan B.”

David Mazzo, NeoStem photo

David Mazzo, CEO of NeoStem, responded by mentioning a possible stock sale and also said the firm had a $30 million equity line of credit.

The company plans to conclude its stock sale on June 2. The stem cell award is on a fast-track to deliver cash to the company within 45 days of approval of the grant. But that requires evidence of the matching funds.

The prospectus for the offering says the four-year trial will cost $25 million, but one analyst says it could cost as up $51 million.  The prospectus also indicated some of the money raised next week could go for purposes other than the melanoma trial.

$15 Million for Calimmune and California Stem Cell HIV Trial

Calimmune, Inc., which has received $8.3 million from the California stem cell agency, today announced it has rustled up another $15 million to help out with the work that the agency is backing.

Calimmune of Tucson, Ariz., was co-founded by a former agency board member and Nobel Prize winner David Baltimore. It is currently engaged in a clinical trial in Los Angeles and San Francisco involving a treatment for HIV.

John Carroll, writing on Fierce Biotech, said,

“Calimmune hasn't had much of a profile outside of the HIV world, but (CEO Louis) Breton is looking to change that. The company has a staff of 40 now, he says, and is looking to expand and possibly strike a partnership deal with a Big Pharma in the space. And unlike some of the leading gene therapy companies in the industry which are targeting tiny populations, Calimmune is tackling a treatment for a disease with a huge, global population of patients. Discussions about million-dollar therapies, he says, won't work for something like HIV. 

"‘Our mission,’ says Breton, ‘is to provide broad capacity; democratize gene therapy for the masses.’"

Calimmune said the latest investors include a “large pharmaceutical company” and Alexandria Venture Investments of Pasadena, Ca. They are in addition to original investors, RA Capital Healthcare Fund LP and Translational Accelerator LLC.

Carroll is right about Calimmune’s low profile. From its earliest days, it has declined to disclose such things as the number of employees. The figure of 40 that was cited by Carroll was the first time it has been disclosed.

(See here, here and here for more information on Calimmune.)

Cedars-Sinai Researcher Snags $5 Million for Stem Cell Eye Research

Another winner in last week's California stem cell awards was scientist Shaomei Wang of Cedars-Sinai, who will receive nearly $5 million for her work to find a treatment for retinitis pigmentosa. 

Shaomei Wang, Cedars photo

The board last Thursday ratified the decision of 15 reviewers who unanimously approved the Wang application. It was one of two awards approved in the first round of CIRM 2.0, the new effort by the agency to speed cash to researchers. It was the first agency award to Wang.

(The other award last week was for nearly $18 million to NeoStem, Inc., of  New York.)

CIRM, as the agency is known, said in a press release that the funds will go for "the late-stage research needed to apply to the Food and Drug Administration for approval for a clinical trial in people. The therapy will involve injecting neural progenitor cells under the retina at the back of the eye. The hope is that this will slow or even halt the progress of the disease."

The press release oddly, however, did not identify Wang as the recipient, only mentioning that the award went to Cedars. In the past, the agency has identified researchers by name in award press releases and has provided information that has included links to summary information about the research.  

Cedars has been awarded $43 million by the agency, not including the latest $5 million. It has had a representative on the CIRM governing board since its inception as do nearly all of the recipients of funds from the $3 billion state program.

Here is a link to a summary of the review of Wang's proposal. Here is Cedars' press release on the award. 

Texas Scientist to Lead Melanoma Study Backed by $18 Million from California

NeoStem, Inc., yes­­­terday announced that University of Texas researcher Merrick Ross will lead the skin cancer clinical trial that California has backed with nearly$18 million.

Ross is a professor of surgery and chief of the Melanoma Section, Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center. Ross also has a California tie. He held a research fellowship in 1984 at the Scripps Research Institute in La Jolla, but virtually all of his career has been in Texas.

NeoStem says the stage three clinical trial will have seven sites in California. It is currently recruiting patients for the 4-year effort for a treatment for metastatic melanoma. It is calling the program the “Intus Study.” 

The firm says patients must be 18 or over have “recurrent metastatic melanoma (Stage III) or distant metastases (Stage IV).” Other requirements must be met. Initial outcomes are scheduled to be reported in January 2017.

Interested persons can find more information here and here.

NeoStem Sees Whopping Jump in Stock Price on $18 Million Backing from California

A graphic depiction of trading on NeoStem stock last week.
Google chart

The stock price of NeoStem, Inc., shot up 28 percent in one day last week after the California stem cell agency approved a nearly $18 million grant to the firm for a potential therapy that “teaches the immune system which cells to attack and kill.”

The governing board of the state research effort awarded the funds on Thursday May 21. The grant is to assist in a third stage clinical trial involving a treatment for metastatic melanoma, the most deadly form of skin cancer. Following the approval, NeoStem’s stock soared from $2.30 to close at $2.95.

The California Stem Cell Report first disclosed the agency’s virtually certain action on Tuesday May 19.

It was an obvious boon for the New York-based company whose CEO, David Mazzo, told the board that the award would help to raise more cash to finance the trial which is expected to cost $45 million to $51 million, according to analyst Yi Chen of H.C. Wainwright.

For the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is formally known, it will be the first time that it has plunged into a stage three trial and the closest it has come to actually bringing a therapy to market.

Jonathan Thomas, chairman of the $3 billion agency, told the board on Thursday that the NeoStem project has “the greatest chance of success for the people of California that we have funded.”

The agency was created in 2004 when voters approved a ballot initiative whose backers raised expectations of quick development of stem cell therapies. The agency has committed more than $1.9 billion for research. Its money for new awards is expected to run out in 2020.

NeoStem, which has operations in Mountain View and Irvine in California, issued a press release hailing the award. The company called the action a “significant endorsement” of its approach which it said has potential application in other types of cancer.

  

The release quoted Randy Mills, president of the agency and former head of Osiris Therapeutics of Maryland, as saying cash would start flowing to NeoStem in 45 days. He continued,

“But that's just the start. We are not just providing financial support; we are also partnering with these groups to provide expertise, guidance and other kinds of support that these teams need to help them be successful.”

Under a new scoring system introduced by Mills, the agency’s blue-ribbon reviewers voted 6-3-5 to fund the program with the three saying the application needed improvement. That action occurred behind closed doors weeks before last Thursday’s meeting when the board ratified the reviewers’ decision on an 11-0 vote. One CIRM board member, Leon Fine of Cedars Sinai, said that one perspective on the reviewers’ voting could be that eight persons thought the application needed more work or should be rejected.

Board member Steven Juelsgaard, former executive vice president of Genentech, raised questions about what might happen if the board rejected the NeoStem application, given that it has only $19 million on hand at last report. Juelsgaard said that was not sufficient to complete the trial.

Mills declined to speculate on what the company might do.

Juelsgaard returned to the subject a few minutes later when Mazzo addressed the board and asked Mazzo about the company’s “Plan B.” Mazzo said the company could go to the “capital markets.” He also said the company had recently negotiated a $30 million equity line of credit.

Mazzo said that the firm is constantly looking for funds and that the CIRM grant would go “a long ways to advancing the trial.”

The vagaries of the marketplace do, however, play a role in the investment community’s view of the company. After the stock jumped 28 percent on Thursday, it dropped 2 percent on Friday.

The 52-week low for the stock is $2.15 and the high is $7.23.

The trial is currently seeking enrollees worldwide, including at seven sites in California. 

UC Davis Stem Cell Program Cited in Sacramento Bee

Here is one of the photos run by The Bee today with a story
about the UC Davis stem cell program.

The Sacramento Bee today published an article on the rise of UC Davis as a major stem cell research center, largely with a $130 million assist from California’s stem cell agency.

The news article was written by the editor of this blog, David Jensen, on a freelance basis. At the time of this writing, the article ranked No. 1 out of 81,000 results on a Google news search using the term “California stem cell.” 

While the piece focuses on UC Davis, a similar impact has been felt at UC Santa Barbara, whose stem cell program has also benefited greatly from CIRM largess.

CIRM Directors Coverage Delayed

Today's meeting of the directors of the $3 billion California stem cell agency will not be covered live by the California Stem Cell Report. Look for a reprise of the session in the coming weeks.

NeoStem Up For $18 Million Melanoma Award from California

California's stem cell agency is expected to make an $18 million bet this week on a treatment by NeoStem, Inc., for a skin cancer that kills 10,000 persons a year in the United States alone.

Up for approval on Thursday is the company's application for an award to assist in a late stage trial that could produce a commercial product before the agency is expected to run out of money in 2020.

NeoStem is based in New York city but has operations in Irvine and Mountain View in California. It acquired California Stem Cell, Inc., in Irvine in April of 2014 for $124 million. California Stem Cell was founded by Hans Kierstead of UC Irvine, who is now president of NeoStem Oncology.

The $3 billion agency did not disclose the name of the company in keeping with its longstanding practice of concealing the identity of applicants.

However, company documents and SEC filings indicated that NeoStem was the applicant. It would be the first award by the agency to Neostem, which is a publicly traded firm.  

The summary of the agency's review posted on its Web site said the funds would go for completion of a stage three trial for a tumor stem cell-targeted immunotherapy for metastatic melanoma, which accounts for 20,000 new cases annually.

The review cited "compelling results" from the phase two stage of the trial. NeoStem has reported separately that its stage two trial had a 72 percent survival rate after two years compared to 31 percent for the control group.

NeoStem said in SEC filings that the treatment is for the most lethal form of skin cancer and has estimated market size of $1 billion.

Helping to develop a marketable product would be a big score for the agency, which has yet to fund a commerical therapy after 10 years and $1.9 billion.

Its money for new awards will run out in 2020 at its current spending rate. No additional funding sources for the agency have surfaced at this point. Being able to cite development of a commercial therapy would be likely to generate considerable enthusiasm for the agency's continued work.

Both reviewers and the CIRM staff recommended approval of the NeoStem application at the CIRM governing board meeting on Thursday.

The action came on a split vote among reviewers, 6-3-5, with six recommending funding and five against funding, according to a CIRM document.. Three reviewers said the application needed improvement.

The CIRM summary of the review said,

"Reviewers considered the lack of mechanistic data and inadequate plan to gain understanding of therapeutic mechanism of action to be a major weakness and expressed concern regarding the ability of the applicant to enrol the proposal pivotal Ph3 (phase three) study as projected."

CIRM said, however, the vote and staff recommendation to fund the research "reflects both the high risk and the clear potential to impact unmet medical need."

The CIRM governing board almost never overturns approval of an award by its reviewers and staff.

The award would be one of the two first approved in CIRM's 2.0 program to fast-track cash to researchers, speed development of therapies and improve the quality of grant applications. The second award  -- $5 million -- is for work immediately leading up to a clinical trial for a therapy for retinitis pigmentosa. Shaomei Wang and Clive Svendsen at Cedars-Sinai in Los Angeles are the likely key figures in that research. Reviewers voted 15-0 to fund the work.   

California Stem Cell Audit: Praise for Mills but More Work Needed on IP, Conflicts of Interest

The California stem cell agency this week received good marks for changes made by its new president, but it is also being told that it needs to improve how it tracks potential royalties and how it prevents grant reviewer conflicts of interest.

A "performance audit" by Moss-Adams, a Seattle business consulting firm, made 12 recommendations for the $3 billion research enterprise. One of the 12 was to implement the unfulfilled recommendations made by Moss-Adams three years ago.  Seven of the 24 from that audit still need more action, the firm said.

On Thursday, the agency's governing board is scheduled to discuss the latest audit at a meeting in Berkeley.  The study is required by state law every three years. The agency's scientific performance, however,  is specifically excluded from being examined. Moss-Adams is scheduled to receive $230,000 from the agency for the audit, which was for the 2013-14 year.

On Sunday, the California Stem Cell Report covered the deficiencies involving disclosures of the financial interests of grant reviewers.

Other areas of concern included the need for better tracking of intellectual property that could mean royalties for the state, more timely review of progress reports from grantees, more timely, formal evaluation of employees and keeping up-to-date on technology related to grant management and agency efficiency.

Under the subject of "commendations," Moss-Adams said that CIRM had "many strengths."  The consultant said the agency has made "significant strides" in three areas: the grant management system, grants process improvements and "organizational culture."

The grants process comment referred to CIRM 2.0, the fast-track funding program initiated by Randy Mills since he became president a year ago. The organizational culture commendation also involved Mills' efforts, but touched indirectly and delicately on the resignation of Robert Klein as chairman and the election of Jonathan Thomas to replace him in June of 2011. 

Moss-Adams reported "enhanced seamlessness" between the president's and chairman's offices. Proposition 71, which created the agency, dictated a controversial dual executive situation that has troubled the agency since its inception.

The audit found significant deficiencies involving the treatment of CIRM employees, some of which have been addressed in a positive way already by Mills. One example cited by the audit involved performance evaluations that are tied to pay increases. It said that evaluations that were scheduled to occur in 2013-14 did not actually take place until January of this year.  

Moss-Adams said the agency also needs to do better in monitoring and protecting its intellectual property (IP), which could generate royalties. Without tight tracking of the IP and inventions funded by CIRM research, the state could lose out on revenue. Backers of Proposition 71 told voters in 2004 that the state could receive more than $1 billion in royalties from CIRM research. So far, none has resulted. 

Moss-Adams said that royalties are now more possible because the agency is backing late stage research that is more likely to make it into the market place. 

Moss-Adams said more work was needed on implementing the seven recommendations from three years ago, including those involving IP, the transition plan to deal with the possible demise of the agency and a grants outcome database. 

Five Public Sites Set for Thursday's Board Meeting of the California Stem Cell Agency

For those who want to participate in this Thursday's meeting of the governing board of the California stem cell agency, five public locations are available.

The actual meeting will be in Berkeley beginning at 9 a.m. PDT. Oher public locations will be in San Diego and Danbury, Conn., and at UC Irvine and Cedars-Sinai in Los Angeles.

Specific addresses can be found on the agenda for the meeting along with instructions on how to listen in on an audiocast. However, the audiocast does not provide the opportunity to comment.

Written comments to the board for the meeting can be emailed to mbonneville@cirm.ca.gov.