With more than 3.0 million page views and more than 5,000 items, this blog provides news and commentary on public policy, business and economic issues related to the $3 billion California stem cell agency. David Jensen, a retired California newsman, has published this blog since January 2005. His email address is djensen@californiastemcellreport.com.
The history of the stock price of Forty Seven, Inc., since it went public in 2018. Google graphic
The stock price of Forty Seven, Inc., California's "don't eat me," cancer therapy firm, today closed at $$93.91 as the state's stem cell agency hailed the firm's performance as "perfect example" of the agency's value to the field and to the people of California. The closing price represented a stunning increase over the firm's record low of $5.53 last October. It came as Gilead Sciences, Inc., and Forty Seven announced this morning that the firm would be purchased by Gilead for $4.9 billion. Maria Bonneville, a spokeswoman for the agency, said,
"Forty Seven, Inc., is the perfect example of CIRM’s value to the field of regenerative medicine. We take pride in our ability to work with our grantees to make them as successful as possible and get them ready to partner in order to fulfill our mission."
Mathew Herper of Stat news interviewed Daniel O'Day, CEO of Gilead, today about the deal. Here is what Herper wrote,
"So why purchase Forty Seven? "'Because it’s novel,' O’Day said, referring to the company’s lead medicine, magrolimab, an antibody against CD47, a protein that cancer cells use to tell white blood cells 'don’t eat me.' The idea is that blocking this protein will allow the body’s immune system to attack cancer cells.
"'We had our eyes on Forty Seven for a while,' O’Day said. Data presented in two malignancies, myelodysplastic syndrome and acute myeloid leukemia, at last year’s annual meeting of the American Society of Hematology showed that the drug was doing 'some pretty special things,' he said. He said Gilead scientists believe that magrolimab could have 'broader utility' because it could be relatively safe and could be combined with other medicines relatively easily."
California's $3 billion stem cell agency, which turned 14 last month, is expected next Thursday to give away another $6.2 million as it continues its efforts to fulfill the expectations of the voters who created it in 2004. Also possibly on tap is an update on the status of efforts to raise privately some $200 million to tide over the agency as it looks forward to 2020 and a possible ballot measure to provide it with another $5 billion. Known formally as the California Institute for Regenerative Medicine (CIRM), the agency expects to run out of cash for new awards in about 12 months. Its award budget for 2019 now stands at $144 million. Presumably, another $28.4 million can be added, which is the uncommitted cash for research left over from this year. The agency subsists on state bond funds approved by voters. Its bond issuance authority, however, is expiring. No other source of funding was provided by voters, and the agency has no expectations of being financed on annual basis by the legislature. The 2004 ballot campaign that created the first-ever such agency in California history raised high hopes a stem cell therapy was right around the corner. CIRM has not yet backed a treatment that is available for widespread use. However, it is helping to fund 49 clinical trials, the last steps before a treatment is approved for the marketplace. The application (CLIN2-11371) before the board next week has already been approved by the agency's reviewers. Normal practice is for the board to ratify in public earlier decisions made in private by reviewers. The name of the recipient has been withheld by the agency until after ratification, as is the agency's standard practice. The proposal seeks to continue a phase one clinical trial to help treat lymphoma. The CIRM summary of the review of the application said the goal of the research is to "ameliorate or accelerate recovery from toxicities related to high-dose chemotherapy followed by
HDT-ASCT for the treatment of lymphoma and other cancers." CIRM said the method would involve "genetically engineered CD31+ cells derived from human umbilical vein tissue (engineered HUVEC)."
"There are currently only a few moderately effective treatments available to reduce the toxic side effects
associated with aggressive cancer treatments – hence a high unmet medical need. New approaches
are urgently needed to both improve quality of life and reduce the risks of high dose therapy."
The summary said that the $6.2 million award would be backed by $2.7 million from the recipient. CIRM Chaiman Jonathan Thomas has been working to raise the private funds to help support the agency beyond next year. He often reports on his progress at board meetings. The CIRM board meeting will be based in Oakland. Offsite locations where the public can participate are located in Stanford and San Francisco. The public can also log in online and ask questions or make comments. Instructions on how to participate are contained on the meeting agenda. If you are not familiar with the procedure, it is useful to log in about 10 minutes prior to the meeting's start (10 a.m. PST) to avoid technical difficulties.
CRISPR was in the news this week, and it wasn't about how you like your French fries cooked.
CRISPR, for those of you who don't know already, is a relatively easy way to edit genes. The technique is used in at least eight research projects backed by the California stem cell agency, totalling about $13.5 million.
What made CRISPR generate the headlines was research -- as Business Insider reported -- that the "blockbuster gene-editing tool has been linked to cancer." The assessment was described as hype by some scientists.
Paul Knoepfler, the peripatetic stem cell blogger and researcher at UC Davis, explored the implications of the findings in an item earlier this week. He wrote,
"To say that CRISPR-Cas9 gene editing might 'cause cancer' seems premature to me so there probably were and are better ways for people to phrase the big-picture meaning of these new papers and others like them that may pop up in the future. However, to be clear safety is crucial, so this is an important development and risks of any potential therapy including gene editing-based approaches should be carefully weighed against potential benefits as trials are designed and then progress."
The California Stem Cell Report asked the agency, which monitors the research it funds, for a list of its projects involving CRISPR. Here is what the agency provided, including the disease focus, principal investigator and grant number.
California's stem cell agency this week took the relatively unusual step of a firing off a double-barreled salute to the beginning of one of its clinical trials -- a $20 million effort based out of UCLA.
Antoni Ribas, UCLA photo
The press release and blog item heralded research by Antoni Ribas, who received the award in 2012 from the California Institute for Regenerative Medicine (CIRM), as the agency is formally known.
The potential treatment deals with the spread of cancer to other
parts of the body, which the agency said is responsible for 90 percent of cancer deaths. Ribas' trial will test a stem cell-based treatment that is better at tracking down and destroying hard-to-treat cancer stem cells. In a news release from UCLA, which is also funding the research, Ribas said,
"(F)ew options exist for the treatment of patients whose cancers have
metastasized due to resistance to current therapies. This clinical trial
will allow us to try a new approach that engineers the body’s immune
system to fight metastasized tumors similar to how it fights germs and
viruses.”
Siwen Hu-Lieskovan, co-investigator, UCLA photo
Maria Millan, interim president of the stem cell agency, said,
“Backed by rigorous science, the stem cell derived T cell immunotherapy being developed by Dr. Ribas and his team has the potential to address advanced cancers that have spread beyond the primary tumor and which are associated with very low survival.
"This trial is the first step in developing a therapy that could alleviate the complications resulting from cancer metastases as well as potentially improving outcomes in cancer patients where there are currently no effective treatment options. We are confident that CIRM’s funding and partnership, in combination with the expertise provided by our Alpha Stem Cell Clinic network, will give provide critical support for the successful conduct of this important clinical trial.”
The $3 billion stem cell agency is actively supporting 33 clinical trials (five involving cancer), which are the last stage prior to approval of a therapy for widespread use. Why the CIRM salute in this case? The blog item by Todd Dubnicoff said,
"The reality is this: the launch of a clinical trial isn’t a beginning.
It represents many years of effort by many researchers and a lot of
funding to take an idea and develop it into a tangible product that has
been given clearance to be tested in people to potentially save their
lives. That’s why this important milestone deserves to be recognized.
More information on the award (DR2A-05309) can be found here. Persons interested in participating in the trial can contact Clinical Research Coordinator Justin Tran by email at justintran@mednet.ucla.edu or by phone at 310-206-2090.
Cellular treatments of cancer received a big media boost this morning with a front page story in the New York Times that said the door is opening on a radical new class of therapy.
The headline on the piece in the print version of the Times in California said,
The peg for the lengthy story was the expected approval of gene therapy for leukemia in the next few months. Grady wrote,
"Companies
and universities are racing to develop these new therapies, which
re-engineer and turbocharge millions of a patient’s own immune cells,
turning them into cancer killers that researchers call a 'living drug.' One of the big goals now is to get them to work for many other cancers,
including those of the breast, prostate, ovary, lung and pancreas.
"'This
has been utterly transformative in blood cancers,' said Dr. Stephan
Grupp, director of the cancer immunotherapy program at the Children’s
Hospital of Philadelphia, a professor of pediatrics at the University of
Pennsylvania and a leader of major studies. 'If it can start to work in
solid tumors, it will be utterly transformative for the whole field.;'"
High in the story (the fifth paragraph), Grady mentioned that cellular treatments are also being studied in connection with glioblastoma, the type of brain cancer afflicting Sen. John McCain.
The Times carried a host of caveats about the likely new therapy, its dangers and even deaths that have occurred during the research. But "studies are forging ahead," Grady reported, despite the fact that they are expected to cost hundreds of thousands of dollars.
The sky is not falling, says a Scripps Research Institute scientist, despite headlines that seem to link "mutation" and "cancer" and "stem cells."
That comes from Jeanne Loring, head of the stem cell program at Scripps, who was writing on the blog of UC Davis stem cell researcher Paul Knoepfler. Loring said,
Loring said she has been on a soapbox on this issue since 2000. She said,
"Every time a scientific report suggests that human stem cells are
dangerous, I feel the need to reassure both scientists and
non-scientists that we should not panic. The sky is NOT falling
(contrary to Henny Penny), and pluripotent stem cells remain valuable for cell replacement therapies."
Loring went into the rather technical reasons for her position as well as identifying issues having to do with not knowing enough about the cells used in research. She also provided some tools for researchers to use to identify cells with "functionally important mutations."
California’s ambitious, $18 million effort to develop -- in relatively short order -- a stem cell therapy for a deadly form of skin cancer collapsed abruptly last week, apparently the victim of “excessively long development timelines.”
Caladrius Biosciences, Inc., the recipient of the California funding, terminated the late stage clinical trial, declaring that other treatments have outpaced its approach and that it is no longer “optimally leverage(d).”
The award last May marked a big advance for California’s $3 billion stem cell research program. It was the first phase three clinical trial for the agency, known formally as the California Institute for Regenerative Medicine(CIRM). A phase three clinical trial is the last step needed before federal approval for widespread use of a treatment. The award came as the agency is entering what could be the last years of its life and is pushing hard to fulfill the promises of the 2004 ballot initiative campaign that led to its creation.
CIRM, which is based in Oakland, Ca., is scheduled to run out of cash for new awards in 2020. The agency expects to intensify its efforts this year at developing a plan to replace the state bonds that it has used since 2004.
The $18 million award to Caladrius was made last spring with considerable ballyhoo. Jonathan Thomas, chairman of the agency’s governing board, said at the time that the treatment had “the greatest chance of success for the people of California that we have funded.”
After the Caladrius announcement, Randy Mills, president of the agency, said in a news release,
“Ultimately this program suffered from the excessively long development timelines common in cell therapy, a fact that further underscores the need for CIRM to work hard to create faster development pathways as called for in our new strategic plan.”
CIRM’s statement also said,
“Only $3 million of the $17.7 million awarded by our governing board had been distributed to Caladrius, which matched that money with $3 million of its own. CIRM will now make the unused $14.7 million portion available to other applicants for investment into projects that accelerate stem cell therapies to patients with unmet medical needs.”
In a document filed with the Securities and Exchange Commission, Caladrius, formerly known as NeoStem, said the end of the trial would lead to layoffs for about 40 employees in Irvine, Ca., the home of what once was California Stem Cell, Inc. That firm was acquired by Caladrius in 2014 for $124 million. It was founded by Hans Kierstead of UC Irvine, who is senior vice president for research and chief science officer of Caladrius.
The company’s SEC filing said,
“The treatment paradigm in metastatic melanoma was transformed during the course of 2015 by the accelerating adoption of multiple immune checkpoint inhibitors used as monotherapy and in combination treatments. These new drugs have significantly improved outcomes in metastatic melanoma and therefore have altered the opportunity for a monotherapy such as CLBS20 in a landscape that is quickly converting to combination therapies. Therefore, we have concluded that, as designed, our current program in metastatic melanoma will not optimally leverage this asset..."
Cancellation of the phase three trial led to a sharp drop in Caladrius’ stock price. It closed at $1.08 on Jan. 6, the day prior to the announcement. Today, the stock closed at 65 cents. The 52 week high for the stock was $4.26 and the low 40 cents. The chair of Caladrius, Robin Smith, resigned on Dec. 23.
California’s stem cell agency is now participating in only one phase three trial, which is not yet recruiting patients. That effort involves a brain tumor program with ImmunoCellular of Calabasas, Ca. The agency is currently participating in a total of 15 clinical trials at various stages.
ImmunoCellular Therapeutics’ stock price shot up 17 percent
today in the wake of formal approval of a $20 million award from the California
stem cell agency for a clinical trial involving a rare brain cancer.
The price has been climbing since last week when the
California Stem Cell Reportfirst disclosed that the company was set to secure
the funding for the phase three clinical trial, the last step before widespread commercialization.
In an interview today, Andrew Gengos, president of the
Calabasas, Ca., firm, confirmed that the trial is expected to cost $40 million to $50 million.
The company has said it will add $34.4 million to the $20 million from the
California Institute for Regenerative Medicine (CIRM), as the agency is
formally known.
Gengos said the five-year trial is expected to get underway
in November with the enrollment of the first patients. He said it will probably
start in the United States with expansion to Canada and Europe. About 400
patients are expected to participate.
ImmunoCellular has not had any revenues since 2010.
Asked about the source of the $34 million, Gengos said the company had $31
million on hand at the end of June with no debt. He added that the company can
access additional cash through the sale of more stock.
In reponse to a question, Gengos said he first became aware
of the possibility of funding the clinical trial with the help of CIRM as the
result of a conversation with a colleague at the J.P. Morgan health care conference
in San Francisco last January.
Gengos followed up by asking an ImmunoCellular co-worker to look
into the process. As the result, the company made its initial application which
CIRM sent back with suggestions for improvement. In the second review,
reviewers voted 9-0 to fund the project.
Gengos told the CIRM board today that the trial would take
five years to complete.
“Frankly, this time period is outside the interest of most
public market investors in terms of their investment horizon and therefore, in
their eyes, handicaps our project compared to other projects that can execute in
a shorter time frame.
“The result is that investment capital is hard to come by
for these types of promising and highly innovative therapies when the
investment horizon is long, and a small company without product revenues is at
the helm.”
Gengos continued,
“I do not think it is an overstatement to say that without
CIRM’s support, this program would not go forward. California’s innovative
biotechnology community needs institutions like CIRM. Clearly – we need CIRM.
Brain cancer patients need CIRM.”
Here is the text of the company’s press release today.
Here is the text of Gengos statement to the CIRM board.
John S. Yu, chairman, ImmunoCellular -- Cedars-Sinai video
Highlights
Second CIRM bet on phase three trial
$34 million in co-funding
Application initially rejected
California’s stem cell agency next week is expected to award
$20 million to a tiny California firm to help finance a phase three clinical trial
of a therapy for a rare brain cancer.
The move would be the $3 billion agency’s second investment
in a phase three clinical trial, the last major hurdle before a therapy can be
offered for widespread public use. The first was an $18 million bet this spring on NeoStem, Inc., now known as Caladrius.
The two trials offer the best likelihood of
fulfilling -- in relatively short order -- the 2004 campaign promises made to voters
when they created the Golden State's stem cell research effort.
In addition to the state funds, the trial would be backed by
$34.4 million in co-funding, according to the California Institute for
Regenerative Medicine(CIRM), as the agency is formally known. Earlier this
year, ImmunoCellular estimated the total cost of the trial could be about $50
million.
The firm's proposed therapy targets glioblastoma, a
fast-moving cancer that CIRM said is “resistant to current standards of care." It has a survival rate of slightly more than one year. Immunocellular said
that about 10,000 new patients are diagnosed each year in the United States.
The treatment is called ICT-107. Immunocellular reported on
its Web site that the treatment is “an autologous (patient-derived) dendritic
cell immunotherapeutic that targets six different antigens (peptides that are
tumor markers) associated with glioblastoma.”
“Though the survival response observed in the Ph1(phase one) trial was
not fully replicated in the Ph2 trial, results are supportive of continued
clinical development and of the Ph3 trial as designed.”
ImmunoCellular has been around with its current focus since
2006 when it acquired its cellular-based technology from Cedars-Sinai in Los
Angeles. John S. Yu, director of surgical neuro-oncology at Cedars, is listed
as the founder of the firm. He is now chairman of the board and chief
scientific officer.
The firm has four full-time employees and four part-time,
including Yu, according to February 2015 filings with the Securities and Exchange
Commission. The firm said,
“We have a number of consulting agreements for clinical
development, regulatory affairs, investor relations and business development.
We outsource all of our drug discovery research, process development,
manufacturing and clinical development to third parties with expertise in those
areas."
ImmunoCellular reports no revenues for the past several
years. CIRM said, however, the firm has promised $34.4 million in co-funding
for the clinical trial.
In an August closed-door session, CIRM’s scientific reviewers scored the
ImmunoCellular application as having “exceptional merit” on a 9-0 vote.
Ratification of that decision will occur in public
next Thursday in a teleconference meeting of the agency’s 29-member governing
board, which includes one representative from Cedars-Sinai.
The board almost never rejects a positive recommendation from its reviewers. The agency also does not release the names of successful applicants in advance of a board vote. The California Stem Cell Report identified ImmunoCellular through other means.
The firm's original application was deemed by CIRM reviewers to need improvement on a
1-9-2 vote and was sent back to ImmunoCellular for revision. The August review summary said,
“(R)eviewers had feasibility concerns regarding the
applicant’s ability to enroll the trial and maintain the reagent supply chain
to support manufacturing of the product. Reviewers also had concerns with the
trial design, which centered around selection of the patient population
targeted in the registration trial and the lack of immune monitoring proposed
in the trial.
“The applicant was provided the opportunity to address these
concerns in a revised application, and their responses and modifications to the
proposal reassured reviewers that the applicant could enroll and conduct the
Ph3 trial as proposed and that, if endpoints are met, the trial design could
support licensing approval by FDA.”
The price of ImmunoCellular stock closed at $0.425 today, up nearly one cent. The 52-week high of the stock was $1.03 and the low 35 cents.
The Stem Cell Blog run by Stanford's Chris Scott carried an interested commentary the other day from Don Margolis, founder of the adult stem cell company, VesCell, who tackles some of the issues related to reprogramming of adult stem cells.
Among other things, Margolis invokes cancer, criticizes "embryonic cheerleaders" (presumably not unborn pom-pom girls) and attacks "censorship" of those who differ with the heralds of hESC.
Margolis also hails the "refreshing" honesty of such folks as Jamie Thomson, George Daley, Doug Melton and Shinya Yamanaka. You can find the piece here.
