Friday, September 21, 2018

California's $72 Million Diabetes/Stem Cell Bet: A New Partner from Massachusetts

CRISPR Therapeutics is the latest firm to become involved in a California-
backed stem cell research effort. It uses gene-editing techniques to devise cures.
The California stem cell agency has invested $72 million in a San Diego firm that is pursuing a a functional cure for diabetes and which announced this week it was moving to dodge a major obstacle facing its potential therapy. 

The firm is Viacyte, Inc., a privately held enterprise that has received more funding by far than any other state-backed stem cell firm. It announced on Monday that it had hooked up with publicly traded CRISPR Therapeutics, Inc., of Cambridge, Mass., to collaborate on a gene-editing treatment that would evade the body's immune response to earlier Viacyte therapies.

In a Q&A with UC Davis researcher Paul Knoepfler, Paul Laikind, CEO of Viacyte, said,
"The advantage of an islet cell replacement therapy that has been gene-edited for immune evasion is simply that patients would not need to take immunosuppressive drugs, which can have side effects. Our main mission is to improve the lives of patients with insulin-requiring diabetes by delivering transformative new therapeutic options. The work we are doing on PEC-Direct, PEC-Encap, and now an immune-evasive approach, known as PEC-QT, are all a part of that mission."
The treatment is principally aimed at type 1 diabetes, which afflicts 1.25 million persons in this country, the stem cell agency said in a piece on its blog about the new collaboration.

Viacyte was one of the earliest firms to receive cash from the agency, officially known as the California Institute for Regenerative Medicine (CIRM). The awards began with only $48,950 in 2008 when Viacyte was known as Novocell.

The arrangement with CRISPR will provide more funding for Viacyte, $15 million from its new partner and possibly another $10 million in the form of a convertible promissory note.

CRISPR's stock closed at $48.99 yesterday, down from $55.36 last Friday. Its 52-week high was $73.90 and its 52-week low $16.16.  The firm announced on Wednesday that it was planning to sell $200 million in common stock.  (Here is a detailed presentation on the firm's strategy and research. Here is a link to one analysis of the firm as an investment.)

In the piece on Knoepfler's blog, Laikind also provided an update on Viacyte's other related research. He said,
"(T)he PEC-Encap (also known as VC-01) product candidate has a bright future! We remain enthusiastic regarding the prospects of PEC-Encap, and are actively working on it. In June, two-year data from ViaCyte’s STEP ONE clinical trial were presented at ADA 2018. Although consistent and robust engraftment has been limited in this study to date, results showed that when engraftment does occur, viable mature insulin-expressing endocrine islet cells can be formed. In some cases, insulin-expressing cells have persisted for up to two years after implantation, the longest time point investigated in the study.
"Building on insights gained during the STEP ONE study, ViaCyte is working with W.L. Gore & Associates, one of the world’s top materials science companies with expertise in medical device development and drug delivery technologies, to modify the Encaptra Cell Delivery System and improve the potential for long-term engraftment. This work has yielded positive results in non-clinical models that, based on clinical experience, have been selected to reflect the response in patients. If the progress continues as expected, we plan to resume STEP ONE trial enrollment in 2019.
"As for PEC-Direct (also known as VC-02), the Phase 1/2 clinical evaluation of that product candidate is also continuing. We are now evaluating patients in the second cohort of the trial. As you know, PEC-Direct has the potential to help the patients with type 1 diabetes with the greatest need."
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Tuesday, September 18, 2018

California's Stem Cell Agency Says It Has Saved Lives and Is Building a Foundation to Save More

Evie Vaccaro, whose life was saved with research backed by the stem cell agency
California's $3 billion stem cell agency took its message this week to the op-ed pages of the
San Francisco Chronicle, declaring that the agency's efforts have saved lives and created a world class network of clinics to develop therapies for all.

Maria Millan, CEO of the agency, and Jonathan Thomas, chairman of its board, said in an op-ed article,
"Have we achieved all we wanted to? Of course not. The first decade of CIRM’s life was laying the groundwork, developing the knowledge and expertise, and refining processes so that we can truly accelerate progress. As a leader in this burgeoning field of regenerative medicine, CIRM needs to continue its mission of accelerating stem cell treatments to patients with unmet medical needs."
The Millan-Thomas article came in the wake of a Chronicle editorial that said the agency, formally known as the California Institute for Regenerative Medicine (CIRM), did not merit additional funding based on its results to date. The Chronicle also carried a lengthy news piece that concluded the agency has not met the expectations of voters who created it through a ballot initiative in 2004. 

The agency expects to run out of cash for new awards at the end of next year. Its hope for survival lie with a yet-to-written bond measure that would appear on the November 2020 ballot. 

Millan and Thomas said the agency is now backing 49 clinical trials and has a host of accomplishments. They said, 
"Today the therapies resulting from the institute’s work are not just changing lives — they are already saving lives.
"Lives like Evie Vaccaro, who is alive today because of a treatment CIRM is funding. Vaccaro was born with SCID, also known as “bubble baby disease,” an immune disorder that often kills babies in their first two years. Vaccaro, now 6, and dozens of other babies were given stem cell treatments thanks to the institute. All are showing improvement; some are now several years past treatment and considered cured. 
"An accident left Jake Javier from Danville paralyzed from the chest down on the eve of his high school graduation. Javier was treated in a CIRM-funded clinical trial. Today, he has regained the use of his arms and hands, is driving a car and is a sophomore at Cal Poly San Luis Obispo. Five other patients treated at the same time as Javier all have experienced improvements meaning that instead of needing round-the-clock care, they can lead independent lives."
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Friday, September 14, 2018

California's $50 Million Alpha Network: Managing the Complexity of Stem Cell Clinical Trials

Clinical Leader, an online publication dealing with clinical trials, yesterday carried a piece exploring the $50 million Alpha Clinic program initiated by the California stem cell agency.

Written by Geoff Lomax, a senior officer at the agency for its strategic initiatives, the article discussed the complexity of stem cell clinical trials and the use of a network of high-powered medical centers to support the novel research and treatment, particularly involving the FDA's programs to speed use of some therapies. 

Lomax's concluding statement in the article said,
"(R)egenerative medicine therapies are treating and curing debilitating and deadly diseases. The FDA’s RMAT (regenerative medicine advanced therapy) and breakthrough designations have created a streamlined environment for product sponsors. To effectively leverage this regulatory policy environment, sponsors must conduct high-quality clinical trials that are often operationally complex.
"Clinical trial networks, capable of managing the array of regenerative medicine technologies, are well suited to manage this complexity. The CIRM Alpha Clinic network is a current highly functioning proof of the concept. Patients with unmet medical need and product sponsors will benefit from the replication of this model nationally and internationally."
The agency, formally known as the California Institute for Regenerative Medicine or CIRM, initiated the Alpha network in 2015. It has since enlarged the effort with a total of $50 million and locations at UC San Francisco, UC Davis, UCLA, UC Irvine, City of Hope and UC San Diego

The Clinical Leader piece said, 
"Recognizing this operational complexity and limitations in clinical experience, the California Institute for Regenerative Medicine (CIRM) pioneered the development of infrastructure to support regenerative medicine clinical trials. Launched in 2015, the CIRM Alpha Clinics are a network of six California medical centers. The clinics conduct FDA-authorized and IRB approved clinical trials. The aim of the network is to achieve greater and more efficient results than the member organizations could if they acted independently. Each of the Alpha Clinics has formed teams with specialized knowledge and experience with regenerative medicine clinical research involving human cell and tissue products. These teams work across their respective centers. As of September 1, 2018, the network is supporting 49 clinical trials — and has supported 60 clinical trials since 2015 — across a range of indications."
Lomax continued,
"This network model of conducting therapeutically diverse clinical trials lies in contrast to the traditional disease-based clinical trial networks that tend to be located in specific clinical units – oncology, cardiology, neurology, etc. The Alpha Clinic teams are horizontally integrated across the centers, so they can support the diverse range of indications where regenerative medicine therapies are currently being evaluated. This technology-based approach facilitates the conduct of clinical trials, particularly in clinical units that may have limited experience with cell and gene therapy products."
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Thursday, September 13, 2018

A Global Stem Cell Perspective: CIRM's Accomplishments in a Field Tougher than Rocket Science

The comments below were emailed to the California Stem Cell Report yesterday in the wake of recent news coverage of the California Institute for Regenerative Medicine (CIRM), as the state's stem cell agency is known. 

The author, who asked not to be identified, has followed the field of stem cell research worldwide since its inception. Here is the text of the remarks.
"As you know, I am usually reticent about putting in my two cents worth regarding CIRM and all the politics swirling around the subject. But the recent published items, as well as radio interviews on the subject, have made me quite uncomfortable. I was not in California when Proposition 71 came on the ballot, so I cannot speak to the hype and campaign promises made that swayed the public. But I have to take issue with some of the nonsense that has been reported as news.   
"Here are some relevant facts: 
"1. People forget that in 2004, the NIH, the major agency in the US funding biomedical research, prohibited funding most of the research needed for this field to move forward. Forget about clinical trials, even basic research was severely curtailed based on unscientific premises. This meant that while other countries could move ahead, US scientists could not step into the arena. Prop. 71 was proposed to unshackle Californian scientists so that they could compete in the research arena on a par with UK, Canada, Australia, and many other countries eager to take advantage of this new discovery.

"2. Lest people forget, the NIH rules at that time were so onerous that anything -- buildings, maintenance, and equipment -- partially or wholly funded by the federal government could not be used to conduct human embryonic stem cell research. Hence the need for CIRM to fund the building of labs, infrastructure and facilities early on. This is not an idea to mindlessly benefit academic institutions, but to allow their investigators to conduct stem cells research without using anything (buildings, equipment, personnel) paid for by federal funds. 
"3. Biomedical research is not like rocket science - it is much harder and much less predictable. Twenty years after the big push by Congress to cure Parkinsons’ Disease by building Udall Centers and mandating funding for this effort - PD is still not cured. Alzheimers Disease has been a target of the NIH for decades; just this year, they are increasing funding for this effort. Yet - no cure in sight. Add to the growing list the “War on Cancer” declared by Nixon in 1971. How much progress was made by 1981? Yet look at all the success today? The fact is that biomedical research is much harder than engineering, and we should be patient instead of whining about the slow rate of progress. It behooves the critics of CIRM to remember that success in research requires time and money. Things are just beginning to ramp up exponentially by the end of the first 10 years. 
"4. Finally, taking a world-wide view of the state of human stem cell research, CIRM has to be considered a great success. CIRM supported the first few clinical trials using human embryonic stem cell products. At the end of 2017, there were 17 clinical trials using human embryonic stem cells. Of these 11 are conducted in the US, and all 11 are initiated in California or conducted in California - this is completely due to CIRM. Of the 11 trials, 6 are directly funded by CIRM, and NONE by the NIH. So without CIRM, there will be few or no clinical trials using this new technology in this country!"
(For some of the news coverage, see here and here.)
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Tuesday, September 11, 2018

SF Chronicle Backs Away From More Cash for California's Stem Cell Agency

The San Francisco Chronicle, which has the largest circulation of any newspaper in Northern California, today said the results generated so far by state's $3 billion stem cell agency "don’t argue for expanded public spending."

The California Institute for Regenerative Medicine (CIRM), as the agency is formally known, expects to run out of cash for new awards at the end of next year. It is seeking to raise privately $220 million to tide it over until November 2020, when it hopes that voters will approve a $5 billion bond measure for continued stem cell research.

However, in a formal unsigned editorial published on its website, the Chronicle said,
"The results to date don’t argue for expanded public spending. The science of stem cell work will need to evolve before more money is provided."
The editorial followed a four-part series  in the Chronicle looking into the state of stem cell research. The final installment last week said the agency had fallen short of the high voter expectations when they approved creation of the agency in 2004. The agency has not yet backed development of a therapy that is available for widespread use, although it currently has investments in 49 clinical trials.

The Chronicle, which says it has a readership of more than 500,000, said,
"California’s pioneering decision to spend $3 billion on stem cell research isn’t producing cures after 14 years of work. Instead, it’s generating a widening scientific field that shows potential but not results.
"It’s a frustrating shortcoming, especially as supporters of the state-sponsored research weigh another bond measure to continue the work. Promised breakthroughs used to sell Proposition 71 in 2004 aren’t panning out, a Chronicle investigation found."
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California's Stem Cell Agency Touts Its "Incredible Ecosystem" of Research

The California stem cell agency today added more of its comments to last week's evaluation of its work by the San Franciso Chronicle in a lengthy piece that said the agency had not measured up to voter expectations.

The forum was The Stem Cellar, the blog of the California Institute for Regenerative Medicine (CIRM), as the nearly 14-year-old agency is formally known. 

Maria Millan, CIRM photo

CIRM CEO Maria Millan, in a Q&A, elaborated on the value proposition offered by the agency and some of the points that were raised in the Chronicle article. Here are two excerpts from the blog. 
"Q: There have been many critics who say it’s taking too long for CIRM to deliver cures, and they expected more. What is your response to these people?
"A: Many of us can relate that relief cannot come quickly enough for our relatives and friends who suffer from debilitating and devastating medical conditions— I believe that is why many of us are at CIRM, an organization whose mission is to accelerate stem cell treatments to patients with unmet medical needs. Through the years, we have enabled the creation of an incredible ecosystem of top scientists and researchers and partnered with patients and patient advocates to pursue this mission. We continually strive to improve and to become more efficient and we share the sense of urgency to harness the potential of stem cell biology to deliver relief to those in need.

"Q: Given all of the differences between CIRM and the NIH (National Institutes of Health), why do you think the reporter compared CIRM to the NIH?
"A: The NIH is the largest health research funder world-wide, has been around a lot 
longer, has a much larger budget >$30B this past year alone and the NHLBI
(National Heart, Lung, and Blood Institute) alone has a $3B annual budget—NHLBI is just one of the 27 NIH Institutes. The reason that CIRM was formed is that the advocates of Proposition 71 wanted to make sure that scientists and developers can pursue vital research opportunities that may not have access to funding by traditional funders, including the NIH. CIRM has a total budget of $3B available to fund research and support operations and we have been managing that budget since the passage of Proposition 71 in 2004. If we consider the number of stem cell trials for given available budget, CIRM has funded a disproportionately higher number of translational and clinical programs in stem cell and regenerative medicine. In fact, the NHLBI has entered into a collaboration with CIRM on their Cure Sickle Cell initiative because of CIRM’s specialization in funding and enabling cell-gene regenerative medicine research. I take this as a validation of CIRM’s value proposition in this new area– acceleration, translation, and clinical trials."
See here for more on the sickle cell initiative.
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Thursday, September 06, 2018

San Francisco Chronicle: California's $3 Billion Stem Cell Program Does Not Measure Up to Voter Expectations

The San Francisco Chronicle, in a long and penetrating look at California's $3 billion stem cell agency, today said the research program has fallen "far short" of the promises made by its backers during the ballot campaign that created the effort.

Written by Erin Allday and Joaquin Palomino, the article said the agency, created by Proposition 71 in 2004, "can take credit for some notable progress," including saving the lives of children with rare immune deficiency diseases. Such efforts have been well supported by the agency, formally known as the California Institute for Regenerative Medicine (CIRM).

"But as thrilling as such advances are, they fall far short of what Prop. 71’s promoters promised." Allday and Palomino wrote.

"Not a single federally approved therapy has resulted from CIRM-funded science. The predicted financial windfall has not materialized. The bulk of CIRM grants have gone to basic research, training programs and building new laboratories, not to clinical trials testing the kinds of potential cures and therapies the billions of dollars were supposed to deliver."

Allday and Palomino worked on the CIRM overview for months, along with three other major pieces on stem cell therapies, both unregulated and those backed by the stem cell agency.  They reviewed the nearly 1,000 grants awarded by the agency and tracked the results, interviewing researchers and patient advocates and quantified the results.

The Chronicle series appeared as the agency nears its financial demise. It expects to run out of cash for new awards next year. The agency hopes that voters will approve a yet-to-be-written, $5 billion ballot measure in November 2020.

The Chronicle noted, however, that much of the research financed by the agency is not likely to resonate with voters.

Nonetheless, the article today contained ample information from the agency about its efforts, including its 49 clinical trials and some high profile results from those trials.  The piece posed the question of whether the nearly 14-year-old program has paid off. And it said,
"It’s not a question that can be answered simply. Science often can’t be measured in quantifiable outcomes. Failures aren’t just common, they’re necessary — it’s impossible to expect every dollar invested in research to lead down a traceable path toward success.... 
"It has helped make California a global leader in the field that’s come to be known as regenerative medicine. Anywhere significant stem cell research is taking place in the state, it almost surely has received support from CIRM."
The Chronicle quoted a member of the CIRM board who has been with it since its first days.
"'What was promised was not deliverable,' said longtime CIRM board member Jeff Sheehy, a former San Francisco supervisor. 'However, I would distinguish the promises from the impact and value. We have developed a regenerative medicine juggernaut.'"
The Chronicle also spoke with Bob Klein, a Palo Alto real estate investment banker who led the 2014 campaign.
"Klein...is unapologetic about the campaign he led. Indeed, as he lines up advocates and testimonials for the coming campaign, his message is familiar: Fund this research and we will save lives. Slow it down and the consequences will be grave.
"'Do you want your son to die? Are you going to wait?' Klein asked recently. 'Is that the price you are prepared to pay?'"
Today's Chronicle piece, roughly 5,000 words long, raises a host of important issues and deals with them in a nuanced and thoughtful manner. It is must reading for all those interested in California's stem cell research effort. 

(Editor's note: An earlier version of this item inadvertently omitted Palomino's name. Allday noted in an email to the California Stem Cell Report: "He played a HUGE role in putting together the CIRM story – he was basically solely responsible for collecting and analyzing the data from CIRM.") Sphere: Related Content

Wednesday, September 05, 2018

'Better Than Hope' to 'No More Cash Without Changes' -- Overviews of California's $3 Billion Stem Cell Program

Looking for a relatively quick, current overview of the activities of the $3 billion California stem cell agency?

You can find it here on the California Stem Cell Report with the links below to recent items growing out of a state legislative hearing.

CEO Millan Makes the Case for California's $3 Billion Stem Cell Research Program

The top executive at California $3 billion stem cell agency, which expects to run out of cash for new awards next year, outlined for state lawmakers last week the benefits of the nearly 14-year-old program.

California Stem Cell Agency Touts its Economic Impact on the Golden State

The California stem cell agency last week told its story to a state Assembly committee on biotechnology, including economic figures from a study financed by the agency itself. 

'Better Than Hope' -- An Advocate's View of California's $3 Billion Stem Cell Research Program

Longtime patient advocate Don Reed appealed to California lawmakers last week to support the state's stem cell research effort, which expects to run out of money for new awards at the end of next year.

A Before and After Story of $138 Million in California Stem Cell Cash

The head of the stem cell program at UC Davis says California is leading the way into a "new era of living medicine," thanks to the efforts of the $3 billion state stem cell agency.

State Lawmakers Hear Story of a Life-Saving Treatment and the California Stem Cell Agency

A father from Folsom, Ca., earlier this month told a state legislative committee about how his baby boy was saved through a clinical trial that was being financed by the Golden State's $3 billion stem cell agency.

California's Stem Cell 'Gold Rush:' Nearly 14 Years of Prospecting

A committee of the California Legislature today examined the state's $3 billion stem cell agency. Officials of the agency and others presented their perspective. Here is the text of prepared remarks by David Jensen, publisher of this blog, who appeared at the invitation of the Legislature. This is a third-party overview that deals with pluses, minuses and policy questions.

A Harsher Look at California's Stem Cell Program: No More Cash Without Changes

California's $3 billion stem cell experiment received a host of accolades last week at a state legislative hearing, but one strong, critical voice was not heard in the proceedings.
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