Alpha Clinic Kickoff: Launch of Capricor Trial for Duchenne in $50 Million California Stem Cell Network

UC Davis this week inaugurated its Alpha Clinic program, part of a $50 million, statewide network created by California's 13-year-old stem cell research agency.

The school kicked off its program with the start of a "HOPE-2" clinical trial for Duchenne muscular dystrophy – a fatal genetic disorder mainly affecting boys and young men. About 200,000 persons worldwide suffer with the affliction. There is no cure. Treatment options are limited.

Craig McDonald
UC Davis photo

The lead trial investigator, Craig McDonald of UC Davis, said in a news release,

"Collaborating with the Alpha Clinic team enables us to capitalize on their research infrastructure and expertise for clinical trials focused on cell-based therapies.

"It complements the skills of UC Davis’ Neuromuscular Research Unit, which is a national leader in conducting Duchenne trials. We believe this unique partnership could be a model for translating stem cell discoveries into meaningful treatments for patients with muscular dystrophy and other serious progressive neurologic diseases.”

The trial will test the safety and efficacy of a therapy developed by Capricor, Inc., of Beverly Hills -- CAP-1002. The state's stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), in 2016 awarded the firm $3.4 million, part of a total of $17.8 million that the firm has received from the state. CIRM has also awarded another $7 million to Cedars-Sinai for early development work that led to the creation of Capricor.  

(Here is a link to the summary of the review of the Capricor application, CLIN2-08334, submitted by Deborah Ascheim, chief medical officer at Capricor.)

CIRM governing board member Jeff Sheehy said in 2016,

"This is pretty much a pure CIRM product. They came into our first disease team to develop the product. We've supported two of the three clinical trials. So if this turns out to be a major success, this will be a real feather for CIRM. We've been with them all the way. So I'm optimistic."

Linda Marban, president of the firm, said in a news release that the research is "one of the very few clinical initiatives to focus on helping boys and young men whose ability to walk has been seriously impaired by the loss of muscle function that occurs as Duchenne muscular dystrophy progresses."

Capricor is a publicly traded firm, whose stock closed at $1.32 today. The 52-week high on the stock was $4.25 and its  52-week low 63 cents.

The Alpha Clinics are one of the signature programs of the stem cell agency. In addition to Davis, UC San Francisco, the City of Hope, UCLA, UC Irvine and UC San Diego are part of the network. UC Davis last year received $8 million from CIRM to help create its program. 

A California Scientist's Eight-Year Journey into the Byways of Dubious 'Stem Cell' Clinics

You could call it the "Knoepfler Effect."

It has bounced noticeably around the country in recent months, leading to headlines in the Washington Post, the Atlanta Constitution, the Los Angeles Times and other outlets in Florida, Seattle and elsewhere.

It involves the activities of dubious, so-called "stem cell clinics" -- enterprises once ignored by the mainstream media, the Food and Drug Administration as well as other regulators, including California lawmakers, and much of the established stem cell scientific community.

Not so today. Here is a sampling of the recent news coverage:

• "How ‘stem cell’ clinics became a Wild West for dodgy treatments"
• "Unregulated stem-cell clinics are proliferating across the United States"
• “There's a problem with stem cell therapy in Florida”
• "Patient lawsuits, federal investigations and a 'virtual' PhD: Inside a would-be stem cell empire"

Paul Knoepfler
UC Davis photo 

Over the last several months, these "stem cell" businesses have come under increasing scrutiny by media and regulators. Much of the credit for the attention must go to Paul Knoepfler, a stem cell researcher and blogger at UC Davis. About eight years ago, he began writing -- largely alone and in isolation -- on his blog about the problem. 

He was convinced that the persons lured into the "clinics" were paying large sums for so-called treatments that did not fulfill their promise and that, in fact, could be dangerous. In one case, Knoepfler went undercover -- sort of. He later tangled politely with the leading newspaper in California's state capital about how it was carrying full page ads from an unregulated clinic.

The watershed moment came in 2016 when Knoepfler and Leigh Turner of the University of Minnesota put a number to the matter -- 570 dubious "stem cell" firms nationwide with California leading the nation with 113. That was the key. Readers and regulators like solid numbers. They help focus attention, providing a hook for action and creating a new understanding.  Knoepfler and Turner's peer-reviewed scientific journal piece was the biggest stem cell story in the country that week.

Knoepfler also learned about the media game. He promptly returned media emails and calls and couched his responses in plain English -- "good quotes," as they are known in the trade.

Knoefler persisted even while some of his peers looked disparagingly at his blogging.  Back in 2012, one told Knoepfler that he was "skeptical of scientific social media with its 'twitting and the blobs(cq)'."

In California, however, his work helped to lead to a new law that forces the "stem cell" enterprises to inform their customers more fully about the nature of what might happen to their bodies.

It is a ticklish business to credit a specific individual with triggering a fresh wave of public attention to new and complex issues, such as stem cells and their dubious exploitation. Turner and others have been involved as well and deserve considerable credit. But Knoepfler was at the forefront and did, in fact, take a few arrows for his work.

The California Stem Cell Report asked Knoepfler for his brief thoughts about his stem cell adventures. He replied,

"Some highlights include times when patients decided not to get risky stem cells for themselves or their kids. I also have enjoyed getting to know so many cool people from diverse backgrounds all over the world I’ve only met because of the blog.

"Seeing things like the new California stem cell clinic law sprout up is exciting too, especially as now other states are trying to follow our state's lead it seems and maybe pass even better legislation. I’m also hopeful to have positive impact at the national level such as by somehow working a miracle to get the FDA to do more overall, but we’ll see how that turns out. 

"If that all sounds too cheery, then as my grandma might have said back in the 70s, 'It’s not all peaches and cream.' 

"There have been downsides too like various threats from clinics or their fans. I also feel like at times I’ve stepped in it with something I wrote or said when I could have avoided headaches if I had been wiser. Anyone can do that, but when you do it publicly such as on a blog then it’s got more bite to it. Doing all this stuff has risks to it. But overall it’s been worth it."  

A final note: People often shrug at the likelihood that they can make change in society. Many scientists as well shy from speaking out publicly, surrendering the public arena to snake oil peddlers. But the "Knoepfler Effect" stands as evidence that persistence and first-class work can, in fact, make a real difference in science and public policy. 

California Hits More Than Half-Billion Dollars in Stem Cell Clinical Trials

The stem call agency has an interactive dashboard on its web site, part of which is seen above.

The California stem cell agency this week boosted the number of its clinical trials to 48 -- representing an investment of $553 million -- with the hope of producing its first widely available stem cell therapy and staving off its own demise.

In a 14-minute, telephonic meeting Thursday, directors of the agency ratified three new awards totalling $32 million and increasing its trials from 45. The applications had been approved earlier behind closed doors by the agency's out-of-state reviewers.

The action left the agency, known formally as the California Institute for Regenerative Medicine (CIRM), with $224 million in uncommitted funds, CIRM said in response to a query. The agency was provided with $3 billion when it was created in 2004 by California voters. The $224 million figure could rise $278 million with "recovery" from cancelled grants.

Nonetheless, CIRM expects to run out of cash for new awards by the end of 2019. It is attempting to raise $220 million privately to tide it over until November 2020, the date when voters may be asked to approved an additional $5 billion in bond funding.

Thursday's brief meeting generated no fresh discussion about the financial future of the agency, which is unique in California history and operates with no oversight by the governor or the legislature. Nor was there any discussion of the applications for research funds. 

CIRM said in a news release this morning that while the agency has backed 48 trials, only 42 are active. It has also funded early stage research in 11 additional projects that moved later into the "clinical trial stage" without additional CIRM support. 

The directors made their award decisions Thursday based on a brief CIRM staff presentation and summaries of the reviews of the applications. 

Links to the summaries, the winners and their awards are below. Go to the summaries by clicking on the application number. Updates on the status of CIRM research can also be found as it progresses by searching on the application number.

Sangamo Therapeutics, Inc., of Richmond, Ca., was awarded $8 million to "test a new therapy (phase one/two) for beta-thalassemia, a severe form of anemia (lack of healthy red blood cells) caused by mutations in the beta hemoglobin gene."

The agency said,

Edward Conner
Sangamo photo

"Patients with this genetic disorder require frequent blood transfusions for survival and have a life expectancy of only 30-50 years."

The company, which announced a secondary stock offering of more than $200 million this week, is providing $15 million in co-financing. Its stock closed at $16.75 on Friday. Its 52-week high is $27.50 and its low $4.25. 

The principal investigator is Edward Conner, chief medical officer of the firm, and the application number is CLIN2-11031. 
The company said in a news release that the work also involved Bioverativ.

Stanford University researchers received $12.3 million and provided $2.3 million in matching funds for a a phase one trial for a CAR-T therapy for "patients with B cell leukemias who have relapsed or are not responding after standard treatments, such as chemotherapy."

Maria Millan, president of CIRM, said in the news release,

Crystal Mackall
Stanford photo

“When a patient is told that their cancer has returned it can be devastating news. CAR-T cell therapy is an exciting and promising new approach that offers us a way to help patients fight back against a relapse, using their own cells to target and destroy the cancer.”

The principal investigator is Crystal Mackall and the application number is CLIN2-10846. 

(Here is the link from Stanford on the award. The link was added on April 30 to this item after its initial publication.)

Morton Cowan
UCSF photo

UC San Francisco researchers received $12 million (with no co-funding) for a phase one trial to test a treatment "to restore the defective immune system of children born with severe combined immunodeficiency (SCID), a genetic blood disorder in which even a mild infection can be fatal" and which is often known as "the bubble baby disease."

CIRM said it has"funded two other clinical trials targeting different approaches to different forms of SCID. In one, carried out by UCLA and Orchard Therapeutics, 50 children have been treated and all 50 are considered functionally cured."

The principal researcher is Morton Cowan and the application number is CLIN2-10830.

Weighing California's Stem Cell Trials: An Update from the Golden State's Stem Cell Agency

A sample from the latest information from CIRM on its clinical trial investments. 

California's $3 billion stem cell agency has posted a fresh overview of the 45 clinical trials that it has invested in, ranging from spinal injuries to kidney transplants.

The update is part of the agency's push to better inform the public as well its governing board of the scope and status of its 13-year-old efforts. The clinical trials carry special weight as the agency faces its demise unless it is successful in raising $220 million privately and winning voter approval of a proposed $5 billion bond issue in November 2020.

The Oakland-based agency, formally known as the California Institute for Regenerative Medicine (CIRM), expects to run out of cash for new awards by the end of 2019. Its only funding has been the $3 billion in bonds approved by voters in 2004. The ballot initiative provided no additional source of financing to carry it into the future.

Clinical trials are critical for the agency as it approaches the date when it must ask for more billions. They are the last stage before a therapy is approved for widespread use by the federal government. But even then, a trial can take years. And nine out of 10 proposed, "normal" -- non stem cell -- therapies fail during the clinical trial process, according to studies.  Stem cell trials are so new that their failure rates has not been fully examined.

CIRM is hoping for results in the next year or so that will resonate with voters and lead them to approve additional funding.

The five-page, clinical trial overview sorts the trial information by disease, dollar amount, benefit and date among other things. (See sample of the layout above.) The agency also has additional useful information on its trials on what it calls its clinical trials dashboard, an interactive web page that allows readers to slice and dice the information.

The fresh document on the trials was released as part of the agenda for tomorrow's CIRM meeting during which its governing board is expected to approve $32 million for three additional trials. 

Stem Cell 'Hotbed:' A CIRM Roadshow in Riverside

California's $3 billion stem cell agency took its message of hope for possible therapies to Riverside this week, part of its continuing outreach program that is increasingly taking on additional importance.

Why? Because the agency is scheduled to run out of cash for new awards by the end of next year. It is hoping to raise $220 million to stave off its demise until November 2020 when the plan is to ask state voters to approve an additional $5 billion in funding.

Writing on the agency's blog, Kevin McCormack, senior director of communications for the agency, was enthusiastic. His headline said, 

"A road trip to the Inland Empire highlights a hot bed of stem cell research"

McCormack wrote,

"It was a packed event, with an overflow group watching on monitors outside the auditorium. The questions asked afterwards didn’t just focus on the research being done, but on research that still needs to be done.
"One patient advocate couple asked about clinics offering stem cell therapies for Parkinson’s disease, wondering if the therapies were worth spending more than $10,000 on....
"The visit was a strong reminder that there is exciting stem cell research taking place all over California and that the Inland Empire is a key player in that research, working on projects that could one day have a huge impact in changing people’s lives, even saving people’s lives."

The stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM), is not exactly a household word among most Californians. Events such as the one in Riverside help to spread the word about its activities to voters who might be considering another funding initiative for the agency. However, these type of CIRM events rarely generate news coverage that can amplify their reach. 

The Riverside event was a case in point. A UC Riverside press release earlier this month led to a four-paragraph item in the Riverside Press Enterprise announcing that the event was upcoming. But no news story has yet emerged from the actual event itself. Indeed, the only news story in the newspaper this month about the benefits of stem cell research involved the Vatican, a Riverside girl and, indirectly, a company, Caladrius Biosciences (formerly Neostem) that was awarded $11.6 million from CIRM. The agency, however, was not mentioned.

Tomorrow, another CIRM event will be held at UCLA to highlight the agency's  $50 million, Alpha Clinic program that brings resources together to focus intensely on stem cell therapies and patient treatment.

Fleshing Out the Details: Inside the California Stem Cell Agency's Fledgling Industry Partnership Program

 California's $3 billion stem cell agency has released details on just what is involved in its new collaboration with industry, giving select companies "direct access" to the hundreds of millions of dollars in research that the state has financed. 

The effort involves creation of "robust data rooms," nondisclosure agreements and licensing templates, among other things, and owes a debt to the agency's moribund, $150 million public-private partnership proposal (ATP3).  The new program is aimed at speeding development of stem cell therapies as the agency faces its possible demise in the next couple of years. 

The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, has dubbed the collaboration as the Industry Alliance Program (IAP). It  already has two partners from the private sector, BlueRock Therapeutics of Cambridge, Mass., and Vivo Capital of Palo Alto, and the agency is looking for more. 

Q & A: Data Rooms and More

Neil Littman, CIRM photo

CIRM disclosed more information about the program in response to questions from the California Stem Cell Report (CSCR). Here is the agency's reply from Neil Littman, CIRM's business development officer. It includes a response to a comment filed last week on the original article by an anonymous reader concerning access to research.

CSCR: "What does 'direct access' to CIRM’s growing stem cell portfolio' mean? Will grantees be asked to share their results with these companies....or will CIRM just give out grantees' proprietary information to these companies?"

Littman:  "CIRM will never share proprietary information without the consent of the awardee and the awardee’s institution. In addition, in order to access non-public information, IAP partners (just like everyone else) will need to execute a confidentiality agreement with the awardee’s institution. 'Direct access' implies CIRM’s role in helping IAP partners navigate CIRM’s large and growing portfolio and facilitating introductions when it is mutually agreed upon by the awardee and IAP partner."

CSCR: "It would be useful to discuss with more specificity this language from the IAP agreements: "...diligence process through template legal agreements, such as non-disclosure agreements and licensing templates, and robust data rooms."

Littman: "What does CIRM mean by diligence process? The term due diligence refers to the process of how a company evaluates technology before making an investment. This is often a lengthy review process where the company evaluates items such as preclinical clinical and clinical data, CMC information, and regulatory correspondence. CIRM will help streamline this process by working with the awardee and awardee’s institution to gather all the information in one place for the collaborator to review (this is commonly referred to as a 'data room').

"Why are template agreements useful to collaborators? The template legal agreements provide standardized language which help save time for both the collaborator and the awardee institution. Many features of the agreements will still need to be negotiated, such as the economics of a specific deal, but the templates serve as a starting point."

Son of ATP3

CSCR: These arrangements appear to be descended from CIRM's ATP3 proposal. How did the partnership program emerge? How did those two companies come to be the first to be involved? 

Littman: "Yes, the IAP is descended from ATP3 and is meant to achieve the same goal: increasing the pull from industry in order to increase the number of partnerships. BlueRock and Vivo Capital were selected for a variety of reasons, including: 1) Demonstrated commitment to advancing stem cell treatments to patients (i.e. they have already made investments in the space) 2) Continued commitment to investing in stem cell programs in the future, 3) They are well capitalized with the ability to invest in CIRM-funded programs."

Text of IAP Agreement

Here is the text of the signed agreement with BlueRock, which was requested by the California Stem Cell Report. The agreement with Vivo is identical.

   California stem cell agency agreement with BlueRock Therapeutics by DavidJensen on Scribd

California's $3 Billion Stem Cell Program Partners with BlueRock and Vivo Capital, Looks for More Industry Collaborators

California's drive to produce a stem cell therapy is ratcheting up a notch with announcement of  two new, global industry partners along with a plan to engage more companies and give them "direct access" to hundreds of millions of dollars in state-funded research.

The California Institute for Regenerative Medicine (CIRM), as the $3 billion state stem cell agency is formally known, said the program represents an opportunity "to bring the most promising stem cell, gene therapy and regenerative medicine programs to market where they can help people with unmet medical needs."

The first two participants are BlueRock Therapeutics of  Cambridge, Ma., with offices in Toronto and New York City, and  Vivo Capital of  Palo Alto, Ca., which has offices in Bejing, Shanghai and Tapei. BlueRock was founded in 2016 with $225 million in backing from Versant Ventures and Bayer AG. Vivo has more than $1.7 billion under management, according to the firm's web site.

In addition to venture capital firms, the agency said its Industry Alliance Program (IAP) is looking for pharmaceutical and biotech partners to give them "direct access to CIRM’s growing stem cell portfolio."

Maria Millan, CEO and president of CIRM, said in a news release,

Maria Millan

"The goal of the IAP is to secure industry partnerships and funding for CIRM’s translational and clinical-stage projects. Our agency provides researchers the initial funding to advance promising projects towards the clinic. Now, we’re going a step further by offering a program that facilitates connections between industry partners and our grantees. These companies can offer the support or additional funding needed to give these promising projects the best chance for success and the best chance of helping patients.”

The stem cell agency is nearing its final days and is looking to fulfill promises to California voters who created it 13 years ago through a ballot initiative. The measure provided $3 billion in state bond funding, but no more. The campaign also generated expectations that stem cell cures were just around the corner. The agency has yet to back a therapy that is widely available.

The agency expects to run out of cash for new awards by the end of next year. A $220 million private fundraising effort is being waged to help the agency along until November 2020. That's when CIRM backers hope that the agency's efforts will excite California voters enough for them to approve $5 billion more in funding via another citizen-based initiative.

Deeper involvement with industry is one way to produce quicker results. Venture capital firms are willing to move fast and bet big on research that they deem likely to produce handsome profits.

BlueRock focuses on cell therapies that target severe brain and heart conditions.  According to Biospace, the company expects its most advanced lead therapeutic, a compound for Parkinson’s disease, to begin clinical trials this year.

Vivo focuses on high quality companies in the United States and China but includes building companies from scratch. 

California also brings something to the game.  Karen Ring, the agency's Internet majordomo, noted last week on the agency's blog,

"CIRM is the world’s largest stem cell research funding institution dedicated to helping patients by accelerating the development of quality stem cell treatments. We’re currently funding 244 active stem cell research programs including 39 ongoing clinical trials."

Neil Litman, the agency's director of business development, said CIRM has a "unique vantage point" because of its broad scope. He said the new program is "essentially a built-in concierge service for the stem cell space."

Media Coverage of Stem Cell Therapy for Blindness Loses Sight of California's $36 Million in Support

Dennis Clegg of UC Santa Barbara, one of the leaders in developing a new stem cell treatment for AMD, speaks broadly about the approach in this 2016 video.

The news this week was good for the $3 billion California stem cell agency, which is facing its possible demise in less than two years.

The stories demonstrated what the CEO of the agency, Maria Millan, calls the "value proposition" of the agency's work for the people of California. But only if the agency is mentioned in the news coverage.

Public perceptions are no small matter for supporters of the research agency, formally known as the California Institute for Regenerative Medicine (CIRM).  They wonder as does Millan: How does the agency get real and robust credit for its work, a likely life-or-death question given the agency's hopes to win voter approval of $5 billion more in funding in 2020?

CIRM says it is on track to run out of cash for new awards by the end of 2019 unless its ambitious fundraising plans are successful. And those are only a partial solution until billions more are provided by California citizens.

This week's "good news" stories generated national attention, albeit relatively modest, about CIRM-funded research that has led to to the first-in-human clinical trial for dry, age-related macular degeneration. The treatment uses technology that was described as "very exciting" by one researcher not connected with trial.

The headline on the New Scientist story on Wednesday said,

"Eye implant improves vision in people with age-related blindness"

Reporter Andy Coghlan wrote, 

"A patch implanted at the back of the eye has improved or stabilised sight in four people with severe age-related macular degeneration. The treatment enabled one 69-year-old woman to read 24 letters on a standard eye chart, when she could previously manage only seven.
"The patch is made of eye cells made from human embryonic stem cells, and it has been designed for treating the 'dry' form of macular degeneration, which accounts for 90 per cent of all cases, and affects 1.7 million people in the US."

Nowhere in the New Scientist story was it mentioned, however, that the state of California, through its stem cell agency, has pumped $36 million into the work. 

Likewise for the Los Angeles Times, whose story also did not mention the agency.  And likewise for articles on MIT Review, MedicalXpress, HealthDay, WebMD, US News and World Report, Futurism and FierceBiotech. The list could go on, but you get the idea.

Even the press release from Regenerative Patch Technologies LLC of Portola Valley, Ca., which holds the exclusive license for the implant, buried the Golden State's contribution in the next-to-last paragraph of a nine-paragraph press release.   Plus the company failed to note that the funding was a not insignificant $36 million.

FierceBiotech did mention some private money that was involved in other AMD research, but ignored California's cash.

Readers not familiar with the traditions surrounding news stories about medical research might wonder why the California support received almost no attention. Generally speaking, the amount of cash and the funding source are all but ignored in such stories with some notable exceptions. How that has come about is not clear, but money talks in most circles. The scientist who has lost his or her appointment by failing to bring in sufficient grants can speak to that.

For the California stem cell agency, it is also likely to be a matter of survival. If it fails to receive the widespread public credit for what it believes is a strong and important body of work, it is likely to wither away in very short order. 

$30 Million Cash Infusion for San Diego Firm, On Top of $20 Million from California Stem Cell Agency

A recent recipient of nearly $20 million from the California stem cell agency is on a financial roll this week as it pursues its efforts to translate what it says are "best-in-class gene therapy technologies into lifesaving cell therapies."

The firm is Poseida Therapeutics, Inc., of San Diego. Last October, it was awarded $19.8 million by the California Institute of Regenerative Medicine (CIRM), as the stem cell agency is formally known.

Poseida said yesterday it has hauled in $30.5 million more. The firm said in a news release that the cash will go to "advance a pipeline of autologous and allogeneic CAR-T immunotherapies, as well as gene therapies, using Poseida’s suite of gene engineering technologies."

The firm said its CIRM-backed "P-BCMA-101(product) is a CAR-T therapy currently in Phase 1 clinical development for relapsed/refractory multiple myeloma, with initial clinical data accepted for presentation at the upcoming AACR (American Association for Cancer Research) Annual Meeting." The firm is also tackling prostate cancer.

Jack Murtha of Health Care Analytics News wrote,

"It’s a good day for Poseida Therapeutics, one of the trailblazing precision medicine ventures that aims to transform cancer treatment through cutting-edge gene-editing technologies. But just how good of a day is it? Try $30.5 million good."

Murtha said the company has now raised more than $80 million for its endeavors, including the CIRM award, venture capital of $11.2 million last August and $23 million in 2015. The bulk of today's funding came from Longitude Capital of Menlo Park.

At the time of the CIRM award last fall, Maria Millan, president of CIRM, described the nature of the problem that Poseida was addressing, 

“Multiple myeloma disproportionately affects people over the age of 65 and African Americans, and it leads to progressive bone destruction, severe anemia, infectious complications and kidney and heart damage from abnormal proteins produced by the malignant plasma cells. Less than half of patients with multiple myeloma live beyond 5 years.”

Last fall, CIRM reviewers, meeting behind closed doors, unanimously approved, 10-0, Poseida Therapeutics application (CLIN2-10395), which included Poseida's commitment to provide $8.6 million in co-funding. The agency's governing board later ratified the decision with no discussion.

A public, CIRM-prepared summary of the reviewers' comments said, 

"Reviewers thought that the proposed product has the potential to provide a very high rate of durable response in myeloma patients. There is strong scientific and clinical rationale for targeting BCMA on myeloma cells. Reviewers thought that the proposed improvements to the CAR T cell platform technology are highly innovative and could enhance the efficacy and durability of the treatment. Reviewers unanimously recommended the application for funding."

Job Openings at California's Stem Cell Agency

The California stem cell agency, which is set to basically expire in less than two years, is looking for a few good folks to continue to help it out.

The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, has posted openings for an associate director of marketing communications and interns in the communications and human resources areas.

The associate director's responsibilities include oversight of the agency's Web site plus additional task. The person will replace Karen Ring, who is leaving to join Weber Shandwick, a major public relations firm. Here is the job information for for the marketing position.

The internships are unpaid and part-time. Here are links to the CIRM information on those openings: Communications,which also includes Web work, and human resources.

Currently the Oakland-based agency has a little more than 50 employees. It predicts it will run out of cash for new awards by the end of 2019 unless ambitious private fund-raising plans are successful.

New Tool for Wading Through California's $2.5 Billion in Stem Cell Spending

The $3 billion California stem cell agency this week added a valuable feature that is aimed at giving better access to information concerning its active research portfolio, which currently runs to more than 160 projects.

The feature is called the Active Awards Portfolio Dashboard. Its development was overseen by Karen Ring, the agency's social media honcho. Writing on the agency's blog, she said,

"This interactive tool makes it easy to search through the active research projects that we’re currently funding, and filter these projects by disease focus, technology type or stage of research."

The new dashboard is a companion to the clinical awards dashboard, also engineered by Ring. The agency's website contains vast quantities of information. The dashboards provide tools that help readers wade through it and ferret out what is most relevant to their individual needs.

The California Institute for Regenerative Medicine(CIRM), as the agency is formally known, has funded 969 projects costing nearly $2.5 billion during its 13-year history . It is slated to run out of cash in 2019 unless ambitious fundraising plans fulfill their promise. 

Parkinson's Patient Advocate Pitches for More California Stem Cell Funding

Sometimes things move quickly at meetings of the governing board of the California stem cell agency, which is formally known as the California Institute for Regenerative Medicine(CIRM).  At the meeting this month, it ended before a patient advocate had a chance to make her voice heard.

She is Jenifer Raub, president of the Summit for Stem Cell Foundation of San Diego. She requested that this web site carry the comments she would have made to the board. We are delighted to provide them below.

“On behalf of Summit for Stem Cell Foundation we applaud the efforts of CIRM to move Stem Cell Research forward. We task you specifically with addressing and funding a stem cell-based cell therapy for Parkinson’s Disease  (PD) Research. There is tremendous enthusiasm within the PD community for an autologous iPSC-based therapy. Parkinson’s Advocates are a vocal group as you well know. Funding assistance from CIRM for an autologous iPSC-based therapy for PD would easily result in Parkinson’s Advocates gratefully voicing support for funding for CIRM on the 2020 ballot.”

The California Stem Cell Report welcomes comments and lengthier commentary from persons interested in the $3 billion stem cell agency. Please send them to djensen@californiastemcellreport.com.

Stem Cell Blog Taking Week Off

The California Stem Cell Report is going dark this week. Look for exciting and thrilling fresh postings next week.

California's Alpha Clinic Stem Cell Program Shares Stories and Results Next Month

Brain cancer is the target of this Alpha Clinic effort 
at the City of Hope, which produced this video.

Come April 19th the topic at UCLA will be "Delivery of Stem Cell Therapeutics to Patients" and will feature much of the work being done at the Alpha Clinics that have been generated by the California stem cell agency.

The day-long program is free and open to the public. Registration is required. The session features researchers from throughout the state, ranging from Mehrdad Abedi of UC Davis to Joseph Ciacci of UC San Diego.

Last year's Alpha symposium was held at the City of Hope and was greeted by a packed house.

The Alpha Clinics are located at UC Davis, UC San Francisco, the City of Hope, UC San Diego and UCLA/Irvine and have been financed by the California Institute for Regenerative Medicine(CIRM), as the agency is formally known, at a cost of $50 million.

The clinics have engaged in 48 clinical trials, many of which draw funding from sources other than CIRM. The idea behind the Alpha program is to bring resources together to focus intensely on stem cell therapies and patient treatment.

The agency says the Alpha Clinics feature:

• "Patient-centered clinical trials with the highest standards of care and research
• "Strategic collaboration with academic and industry teams developing innovative stem cell therapies 
• "Leveraging of resources to promote efficiency, acceleration and increased chances of success"

UC Davis and UC San Francisco were added to the list of Alpha Clinics last September. 

Potential Death of California Stem Cell Program Hangs Over Its Performance Evaluation

The looming demise of California's $3 billion stem cell research effort dominated today's meeting of its governing board, which was told both that the agency has made "incredible progress" but needed to do better.

The occasion was the presentation of a $230,000 performance audit required by state law, a task performed by the firm of Moss Adams, one of the largest accounting and consulting firms in the world.

The firm's 38-page report targeted fund-raising, retention of staff and better utilization of board members in its recommendations for improvement and called for a more concrete plan for raising more than $200 million. Excerpts from the report can be found here and an earlier story on the audit findings here.

In its oral presentation, Moss Adams representatives had a number of good things to say about the stem cell agency, formally known as the California Institute for Regenerative Medicine (CIRM). They cited the agency's "incredible progress" and said "we usually see a lot of good things here."

It was the third go-around for Moss Adams, which has performed all three of the CIRM performance audits. (See this for links to the previous audits.) Today's presentation, however, focused more on the issues surrounding the agency's end within a few years, unless ambitious fundraising plans are successful.

The agency expects to run out of cash for new awards next year unless it is successful at raising $200 million from private contributors. That would take care of the agency's needs until a possible $5 billion bond measure might be approved by California voters in 2020.

One board member, Jeff Sheehy, also a member of the San Francisco board of supervisors, raised a number of critical questions, seeking more details about the fund-raising effort. He said there seemed to be a "lot of uncertainty" about it.

Jonathan Thomas, chairman of the agency, said a fund-raising plan is in place. He is leading the effort and being assisted by two other employees. He said some board members have been engaged and he plans to consult with all 29 board members.

David Higgins, a board member from San Diego, asked Thomas about a "double-edged sword" that could come into play because of a successful fund-raising effort. Higgins said the public might be more likely to oppose to a new bond measure if the $200 million is raised, reasoning that public funding was not needed in light of private support. Thomas said he did not think that was a major problem.

The Good and the Not-So-Good: Excerpts From an Evaluation of the California Stem Cell Agency

The latest performance audit of California's $3 billion stem cell agency reports both pluses and minuses on the agency's work. Here are some excerpts from the $230,000 study, the third such audit of the California Institute for Regenerative Medicine (CIRM).

"CIRM has a collaborative, engaged, and performance-oriented culture. Managers, Board members, and staff report improved morale and a more collaborative culture since CIRM 2.0 implementation. CIRM appointed a new president in 2014 and again in 2016. Turnover is often elevated during times of leadership transitions, as noted in 2014 and 2015. However, CIRM’s turnover rate dropped to 10 percent in 2016, suggesting stability in the organization’s leadership and culture."

"CIRM’s uncertain future funding results in employee concerns related to job security. These concerns can, in turn, translate into poor employee morale and reduced organizational productivity. Employees facing potential layoffs often experience elevated stress and anxiety that can become evident in their day-to-day interactions with colleagues and grantees. Because individual employee performance and team performance impact overall organizational performance, declining employee morale can negatively impact CIRM’s ability to efficiently and effectively achieve its mission."

"CIRM’s strategic plan emphasized that CIRM is patient-centered. As such, CIRM has increased its stakeholder engagement, particularly with patient advocates. The agency hosts patient events and trainings across the State of California and has at least 1,000 patient advocates registered. Additionally, CIRM’s Science Officers now proactively search for viable projects, helping engage researchers and increase the quality of proposed grants." 

"As CIRM’s Proposition 71 funding is exhausted, the role of the Communications Department should be elevated to serve a strategic function in educating the public. It is imperative that members of the public are aware of and understand CIRM’s activities and impact while CIRM remains fact-based and objective about its role as a state agency. To achieve this, CIRM should establish metrics focused on external communication and public awareness. Examples of these metrics include: Number of posts on social media accounts, number of press mentions, follower growth on social media accounts, number of 'likes' or 'shares' on social media accounts, growth in website visitors, citations of CIRM-funded research in publications These metrics provide insight on the organization’s communications output, reach, and engagement with audiences beyond patient advocates."

"With the implementation of CIRM 2.0, the organization improved many of its processes to be more efficient and effective. Examples of key process improvements include: ... Establishing “The Wall” by developing a policy clarifying the roles and responsibilities of CIRM employees within and outside the grant review process to ensure it remains fair and impartial.  Streamlined the review summary process by reducing the time to summarize grant applications from six weeks to approximately three weeks.  Reduced grant processing time by reducing the time required to process grants from 22 months to 120 days.  Incorporated milestone-based payments in contracts by shifting the responsibility for project progress to grantees and ultimately holding them responsible for achieving research objectives."

"The ICOC is a large, statewide governing board, with 29 members located across California. There are inherent challenges to this structure: Geography limits the ability of some members to participate in Agenda Item #8 ICOC Meeting March 13th, 2018 California Institute for Regenerative Medicine FY 2016-2017 Performance Audit  17 person and interface with CIRM staff; individuals on a large board may feel less personally responsible and therefore less inclined to participate; and it is difficult for officers and committee chairs to meaningfully build relationships with and identify the best roles for such a large number of members. This is evident in committee participation; while CIRM leverages ICOC expertise through standing and ad-hoc committees, which is a best practice, some members serve on multiple committees while others serve on none. In addition to these challenges, changes to CIRM’s conflict of interest policy in 2013 eliminated the ability of institutional members to participate in grant funding votes. This has limited their overall participation, and several ICOC members reported a reluctance to participate in discussions. Both ICOC members and CIRM staff reported a decline in the engagement of institutional members in all discussions, not just those related to grants."

"In its transition plan, CIRM leadership identified $200 million in additional required funding to continue operating at existing capacity between 2019 and the potential bond measure in 2020. This additional funding would enable the organization to maintain current annual grant awards and staffing levels. Currently, key board members are leading fundraising efforts, which have remained largely confidential. In order to secure this significant amount of funding, additional resources are likely required to demonstrate CIRM’s funding needs, seek donors of varying size and requirements, and provide overall support for fundraising efforts."

"Because the level of funding required to sustain CIRM’s operations is significant, CIRM should develop a formal fundraising plan to identify required resources, activities, and strategies. CIRM’s fundraising plan should identify additional resources and support within the organization required to help potential funders understand the benefit of their investment. For example, the role of the communications team could be expanded to develop fundraising materials that detail CIRM’s goals, plans, and successes as well as funding requirements."

"Transition plans and associated strategies should continue to be deployed as living documents that are continually updated and available to Board members, staff, and external stakeholders. Future iterations should also include organizational structure options during a potential wind-down process. For example, grant funds are currently expected to be exhausted by 2019; grant monitoring, management, clinical trials, and closeout will continue past that date; and intellectual property reporting will be required for 10 years. Eventually, some CIRM activities could be transferred to another state agency. As the transition proceeds, stakeholders and grantees should be made aware of staffing changes to help preserve continuity."

Performance Audit of California Stem Cell Agency: Improvements Needed in $200 Million Fund-Raising Program, Staff Retention and Use of Board Members

A performance audit of California's $3 billion stem cell agency says that more needs to be done to retain the agency's staff as well as exploiting the talents of  board members as the research effort nears what could be its demise.

"There is a significant potential for staff attrition as CIRM plans for a potential wind-down," the $230,000 study by Moss Adams declared. CIRM is the abbreviation for the agency's official name,nthe California Institute for Regenerative Medicine.

The 38-page report also said that expertise of  the 29 board members "could be more effectively leveraged, especially since strong board engagement will be particularly important during organizational transition."

CIRM has estimated it will run out of cash for new awards in 2019 unless ambitious fund-raising plans are successful.  Its ultimate hope is that California voters will approve another multi-billion dollar bond measure in November 2020. To bridge the financial gap between 2019 and the end of 2020, the agency is seeking to raise more than $200 million.

Loss of employees has long been a concern of the agency as it confronts the expiration of the bond funding provided by the ballot initiative that created the program in 2004.

The performance audit said the agency should be "building on efforts to date, continue to regularly communicate transition plans to staff and consider strategies to retain employees, including implementing staff development programs, recognition and reward opportunities, work-life balance initiatives, and cross-functional initiatives."

Beyond its recommendations, the audit had praise for the agency. One example involved its "culture." The report said,

"CIRM has a collaborative, engaged, and performance-oriented culture. Managers, board members, and staff report improved morale and a more collaborative culture since CIRM 2.0 implementation. CIRM appointed a new president in 2014 and again in 2016. Turnover is often elevated during times of leadership transitions, as noted in 2014 and 2015. However, CIRM’s turnover rate dropped to 10 percent in 2016, suggesting stability in the organization’s leadership and culture."

Moss Adams, however, also said more can be done. It said the agency should "develop succession plans for the chair and vice chair, document knowledge of individuals serving in leadership roles, and continue to identify potential highly qualified prospective (board) members."

The audit recommended improvements in the agency's fund-raising efforts. It said the agency has not "formalized its ($200 million) fund development plan." The audit recommended creation of "a formal development plan that identifies roles and responsibilities and the timing of fundraising activities to meet CIRM’s programmatic and administrative funding needs."

Moss Adams additionally recommended improvements in measuring the performance of the agency's public relations program. It said,

"CIRM does not have metrics associated with the effectiveness of the agency’s communication and public education strategy. Recommendation: Develop communications and public education metrics that are integrated into CIRM’s quarterly reporting."

The study, which is required by state law, is the third conducted by Moss Adams. It will be discussed at Tuesday's meeting of the agency's board. The agenda for that meeting said the agency will have a response to the audit findings, but that document is not yet available on the CIRM web site.

The audit, which is required by state law, is the agency's third. Links and excerpts from items involving the previous two can be found here. 

Interested parties can participate in the meeting at 16 different locations throughout California. The  locations can be found on the agenda, but more specifics may be necessary for those who want to attend. They can be had by sending an email to info@cirm.ca.gov.

California Stem Cell Performance Audits and More: Public Has 16 Golden Opportunities to Weigh In

Californians throughout the state next week will have what appears to be a record number of opportunities to participate -- albeit remotely -- in one of the more important, regular public meetings involving the $3 billion state stem cell agency.

The occasion is the March 13 meeting of the governing board of what is known formally as the California Institute for Regenerative Medicine or CIRM. The meetings of the CIRM governing board are the single most important public events that the agency holds.

The board has 29 members. Fifteen of those members will be participating remotely in next week's session, which means that the public can participate as well from those locations in addition to the physical site of the meeting at CIRM HQ in Oakland. The remote locations range from Fresno to La Jolla  and from Riverside to Elk Grove.

And if you are in New York City, you can weigh in from there as well. One of the agency directors will be hooked up from the Big Apple.

During the meeting, the board solicits public comment on each item under consideration plus general comments as well.

The top item on the agenda is the triennial performance audit of the agency, which in the past has

Graphic by Shopify

reported checkered but improving results in the last two reports. Conflict of interest issues surfaced in the last audit(see below).  In 2012, the audit, required by state law, identified 27 areas where improvements were needed.

The actual audit for this year has not yet been posted on the CIRM web site but is likely to pop up any day now.  The audit, which is required by state law, cost the agency $230,000, bringing to $694,944 the total that the agency has spent on its three performance audits.

If you are interested in attending at the remote locations, check the addresses in advance. Sometimes not enough specificity is provided. But an email to info@cirm.ca.gov will provide full directions.

Here is a link to the 2017 CIRM request for a proposal to conduct the performance audit.

Below are excerpts and links to previous items on the two earlier performance reports. At the end is a comparison of performance audit findings to results from other studies of the agency.

SUNDAY, MAY 17, 2015

Conflict-of-Interest Failings Reported in Application Reviews at California Stem Cell Agency

Conflict-of-interest issues have dogged the $3 billion California stem cell agency since its inception, and they are surfacing once again this week in a report commissioned by the agency itself.

This time the matter is being brought up by Moss-Adams, LLP, of Seattle, a business consulting firm that is being paid $230,000 by the agency to conduct a "performance audit."

In a report to be discussed at a CIRM governing board meeting on Thursday, the firm said it discovered serious problems dealing with the reporting of the interests of the agency's blue-ribbon reviewers.

TUESDAY, MAY 19, 2015

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.

SUNDAY, MAY 17, 2015

Conflict-of-Interest Failings Reported in Application Reviews at California Stem Cell Agency

Conflict-of-interest issues have dogged the $3 billion California stem cell agency since its inception, and they are surfacing once again this week in a report commissioned by the agency itself.

This time the matter is being brought up by Moss-Adams, LLP, of Seattle, a business consulting firm that is being paid $230,000 by the agency to conduct a "performance audit."

In a report to be discussed at a CIRM governing board meeting on Thursday, the firm said it discovered serious problems dealing with the reporting of the interests of the agency's blue-ribbon reviewers.

THURSDAY, MAY 24, 2012

CIRM Directors Pleased with Performance Audit Findings

The $3 billion California stem cell agency received a "very favorable" performance audit report compared to other government agencies, CIRM directors were told today.

Representatives of Moss Adams, which was paid $234,944 by CIRM for the study, made the comments during a presentation today to the agency's 29 directors. During their comments, CIRM executives and directors focused on the favorable aspects of the findings of the six-month study.

TUESDAY, MAY 15, 2012

IP to Grant Oversight: Study Calls for Host of Improvements at California Stem Cell Agency

The $3 billion California stem cell agency is laboring under a range of problems that include protection of its intellectual property and management of its nearly 500 grants plus an inadequate ability to track its own performance, a seven-month study said yesterday.

The performance audit by the Moss Adams accounting firm of Seattle, Wash., made 27 recommendations for improvements, including more effort to ease strain connected to the agency's controversial dual executive arrangement. The study said that the nearly eight-year-old agency has many "opportunities" to "enhance performance reporting and decision making, strengthen effectiveness and efficiency, retain essential human resources and leverage technology."

In response to the report, the stem cell agency said, "(M)anagement concurs with the findings and recommendations....The recommendations are focused and constructive. CIRM is already implementing many of these recommendations, and we will be investigating the others in the coming months."

--

Here is a link to the California state controller's comparison of the findings of the 2012 performance audit to previous findings from a number of enterprises ranging from the National Academy of Sciences to the state's Little Hoover Commission. 

Aussie Bioethics Web Site Negative on California Stem Cell Royalties

The California stem cell agency and its royalty news drew attention today from down under in an article that did not exactly view the research effort with warm regards.

The piece appeared on the bioethics blog called Bioedge and was written by Michael Cook, who publishes the web site. He picked up on American news about the royalty matter, largely from the California Stem Cell Report, but also from the $3 billion agency itself.

Cook described the critics as scathing. He concluded,

"During the campaign for Proposition 71, supporters strongly argued that destructive research on human embryos was absolutely necessary for the science to proceed and that cures would certainly come. Almost 14 years later, there have been no cures. The royalty cheque was for a potential therapy for glioblastoma, a deadly brain tumour – but even this not on the market yet. Thus far, it has only passed Stage I clinical trials and been written up in glowing terms in O, The Oprah Magazine."

Full Text of Comments Summarized in Sacramento Bee Royalty Article

Below is the full text of the California stem cell agency response to questions from the California Stem Cell Report in connection with today's article in The Sacramento Bee concerning stem cell agency royalties. The full text of comments from Marcy Darnovsky and Bernard Munos were carried earlier in this piece on the California Stem Cell Report. The quote from Jean Loring of Scripps is verbatim from a comment she made on this item on the California Stem Cell Report. 

Comments from Maria Millan, CIRM CEO
"We view this initial payment as a 'mile marker' and not the destination. It is a good sign that we are going the right direction to a worthwhile destination - treatment and cures for patients with unmet medical needs. The royalty payment is only a piece of the intended return to California. The true return is in treatments & cures and the alleviation of human suffering and the mitigation of the financial burden of the multitude of diseases that CIRM is targeting."

Are there any other royalty possibilities in the pipeline for the next 12 months?

"Once there has been a cheque it means the grantee licensor has exceeded the $500,000 exemption so any subsequent payments to them trigger additional payments to the state. As regards future payments we have already identified another potential payee and are working with the grantee on the calculations involved in determining payment."

What time period does that royalty cover? In other words how long has the licensing been in effect, if that is the proper way to look at it?  

"For this particular payment from City of Hope this covers 4 license agreements over the last 2 years."

Is there anything else that CIRM wants to add to shed more light on this subject? 

"It wasn’t anticipated that revenue sharing would repay the $3b given to us to fund stem cell research in California. The only way that would have been possible is to demand such a high return from any funding we offered that very few companies would be willing to take the money. It would have completely undermined our mission of accelerating stem cell therapies to patients with unmet medical needs. It's also worth noting that an independent Economic Impact Report prepared in 2008 predicted that these kinds of payments would take many years to appear, even saying: “For example, tax receipts were modeled to commence shortly after funding under the proposition began, while improvements in health were modeled as becoming possible in as few as five or as many as 15 years, and receipts from intellectual property only beginning in the latter half of year 14. So, we are on track for where experts predicted we would be."

Sacramento Bee, Royalties and California Stem Cell Payoff

The Sacramento Bee this morning carried an article by this writer on the California stem cell agency and its first $190,345.87, royalty check. The article is aimed at a more general audience including policy makers in the state Capitol. Here is a link to the piece, which carries this headline on The Bee web site:

 "Will California's $3 billion in stem cell spending pay off? First royalty check arrives"

The full text of comments summarized in the piece will be carried later today on the California Stem Cell Report.