Embedding the Power of Stem Cell Therapies: California's Efforts and the Quest for $5 billion More

Everett Schmitt, photo by Meg Kumin

California's $3 billion stem cell agency has financed a lot of research that winds up as dense, inaccessible articles -- at least to the general public -- in costly scientific journals with imposing pay walls.

Sometimes, however, stories of hope and stem cell progress do emerge that are likely to resonate with the state's citizens. They are the folks who voted to create and finance the agency in 2004 and who are expected to be asked again for more billions next year.

One such example involves the cases of Evangelina Padilla-Vaccaro of Corona, Ca., Ronnie Kashyap of Folsom, Ca. From birth they suffered from what is known as the "bubble boy" disease.

Both children were born with severe combined immune deficiency (SCID) that is ordinarily fatal. But as the result of clinical trials that were backed with millions from the stem cell agency, both are still alive today. (See here and here.)

The agency is formally known as the California Institute for Regenerative Medicine (CIRM). It has a blog called The Stem Cellar. Today it published an evocative piece written by the mother of another child with the "bubble boy" affliction. 

In her case, the work that has saved her son's life was not financed by CIRM. But the agency carried her story as a powerful affirmation of the importance of stem cell research, wherever and however it is supported. 

Kevin McCormack, director of communications for the agency, wrote, 

"CIRM's mission is very simple: to accelerate stem cell treatments to patients with unmet medical needs. Anne Klein's son, Everett, was a poster boy for that statement. Born with a fatal immune disorder Everett faced a bleak future. But Anne and husband Brian were not about to give up. The following story is one Anne wrote for Parents magazine. It's testament to the power of stem cells to save lives, but even more importantly to the power of love and the determination of a family to save their son."

Anne Klein's article is just what supporters hope will be embedded in the hearts of voters come November 2020 when the next round of financing for CIRM will be on the ballot. 

These sorts of stories, however, have received little attention in the mainstream media, whose reporting resources are ever-diminishing. The media are hard-pressed financially and otherwise nowadays as their once highly profitable business models have been hard hit by the impact of the Internet. 

Nonetheless the agency is assiduously pumping out information and stories on what it calls its value proposition. Here is the final line in the item that CIRM published today:

"You can read about the clinical trials we are funding for SCID here, here, here and here."

Proven Value -- California's Stem Cell Agency Garners Praise in State's Largest Newspaper

California's $3 billion stem cell agency scored a significant media win this morning with an endorsement from one of its harshest critics, a Pulitzer Prize-winning columnist in the state's largest circulation newspaper, the Los Angeles Times.

Michael Hiltzik, who has written two books on massive public projects, wrote in the Times,

"California’s stem cell program has proved its value to the state and to science. It has earned the opportunity to show what it can achieve with an additional 10 years of life and billions more."

Hiltzik's piece appeared this morning in the print version of the newspaper, which says it has a readership of 2.1 million in the print version alone on Sundays. Hundreds of thousands more would be added online, where the column surfaced on Friday. 

Hiltzik began his column with some very bright news for the agency, known formally as the California Institute for Regenerative Medicine(CIRM). He said that Jonathan Thomas, chairman of the agency, told him that a CIRM-funded cure is headed for the marketplace. Hiltzik described it as "a major achievement."

He wrote,

"A stem cell-based cure developed by a team at UCLA for a rare disease — a 'bubble baby' disease that deprives children of a functioning immune system — is on a path toward expected approval by the Food and Drug Administration as early as next year. It would be the first treatment funded by the program to reach the market."

The achievement would come as the agency faces what Hiltzik called an "existential inflection point." CIRM expects to run out of cash for new awards later this year. The agency was created by voters in 2004 with $3 billion that the state borrowed.

The agency's existence depends on whether voters approve an additional $5 billion in additional bonds that would come from a yet-to-be-written ballot measure on the November 2020 ballot. Voters will need to be convinced that the agency has not frittered away its original $3 billion.

Hiltzik noted the agency's "ups and downs," including hype, conflicts of interest concerns and the affordability of stem cell therapies. He said a new ballot initiative offers an opportunity to make improvements in CIRM's operations.

Hiltzik wrote, 

"Klein told David Jensen of the California Stem Cell Report that he is contemplating a provision in the next initiative for “funding the infrastructure to work on access, to work with insurance companies, to work with Covered California, to work with Medicare, to make sure that there’s access, to make certain that public hospitals and public clinics in California get discounted prices.” That would be worthwhile, if it can be done."

Like most state agencies, CIRM labors invisibly. Its story and value proposition receive little public attention despite its attempts at ground-breaking science. Reporters are rarely seen at its meetings. Few articles are written about its affairs. 

That will change somewhat come the 2020 election season. However, media coverage will be dominated by national politics since it will be a presidential election year.  Given the scarce resources of the media nowadays -- along with other, expected, pressing California matters in the 2020 election -- stem cell research is unlikely to be on any front page (print or electronic) except infrequently, at best. 

Nonetheless, Hiltzik's column will be one of the key pieces that other journalists will dredge up electronically next year as they research ballot initiatives. And how the Times and Hiltzik have framed CIRM's work will be an important element in how other news stories are shaped. 

Looking Back and Forward at the California Stem Cell Agency: 1,000 Awards, $2.6 Billion, 1,200 Patients in Clinical Trials

A CIRM slide from tomorrow's presentation
on the stem cell agency's work.

The California stem cell agency has whomped up a fulsome presentation on its progress since it was created in 2004 and plans to unveil it at a public meeting tomorrow in Oakland. 

The presentation covers everything from cell therapy to de-risking stem cell investing for biotech companies. Maria Millan, CEO of the $3 billion enterprise, will run through the agency's 1,000 awards and 53 clinical trials during tomorrow's meeting of the governing board of the research effort. 

Her presentation comes at an increasingly critical time for the agency. It expects to run out of cash for new awards later this year. It is attempting to raise $220 million privately to help tide it over until November 2020, when it hopes to persuade California voters to give it another $5 billion. 

The agency, known formally as the California Institute for Regenerative Medicine (CIRM), is making the meeting available to the public through its usual Internet audiocast in addition to teleconference meeting sites in Riverside, La Jolla, South San Francisco, Fresno, San Diego, Palo Alto and two in Los Angeles.  That is in addition to the main meeting site in Oakland. (Full directions are on the meeting agenda.) The public can also ask questions via the Internet or the teleconference locations. 

Also up for tomorrow's meeting is discussion of possibilities of changes in CIRM's operations that might be embodied in a ballot initiative in 2020. Two governing board committees mulled over a wide range of options at a session last week, but no decisions were made. The measure is yet to be written but will need to be officially filed later this year. 

"Natural Killer" Cells Score Points for $10.6 Million California Stem Cell Investment

This item has been removed because of inaccuracies in its reporting. The information in the item is under review.

The FDA and the Loss of Gottlieb: What Does it Mean for Stem Cell Research?

Scott Gottlieb at his earlier Senate confirmation hearing

"Panic Attack" --That's what the headline this morning said about the resignation of Scott Gottlieb as head of the Food and Drug Administration(FDA). 

The STAT article addressed the general biotech field and its worries. Gottlieb's departure, however, also creates some uncertainty involving California's $3 billion stem cell agency. Known as the California Institute for Regenerative Medicince (CIRM), the agency is backing 51 clinical trials, all of which are regulated by the FDA.

STAT is one of the more authoritative outlets dealing with medical research news. Its Gottlieb piece reviewed his impact on stem cell and regenerative medicine and what his loss might mean. The full headline said, 

"Scott Gottlieb's Sudden Resignation Will Give Biotech a Panic Attack"

The article by Matthew Herper and Adam Feuerstein said,

"Without Gottlieb at the helm, there is uncertainty. And there is nothing that scares investors and biopharma more."

Most of the news coverage of Gottlieb's surprise resignation focused on his efforts regarding vaping and opiods.  But STAT was not alone on discussing the stem cell/regenerative medicine issues. A piece on Politico said, 

"Gottlieb worked to advance cell and gene therapies, a promising new area of medicine. Under his leadership, the FDA put out a framework for regenerative medicines, designed to accelerate the approval of the most promising gene therapies. At the same time, Gottlieb balanced promoting legitimate new treatments with crackdowns on bad actors who were taking advantage of patients by marketing unapproved, unproven and potentially dangerous treatments."

In California, the state has invested roughly $2.5 billion so far in stem cell research with goal of bringing products to market. That is a process that heavily involves the FDA.

Indeed, a top official of the FDA will be speaking next month at a San Francisco conference sponsored by the agency and UC San Francisco. The topic? "Regulation and the Office of Cell Therapy and Gene Therapies Expedited Reviews"

It is far from clear what will emerge at the FDA concerning regenerative medicine or whether Gottlieb's approach will continue.  President Trump may leave the post vacant for some time. He will be heavily lobbied by interests that have opposed Gottlieb's more visible efforts concerning vaping and opiods. 

Trump also will feel pressure from the regenerative medicine industry. But given the multiplicity of issues facing the president, the FDA is not likely to be high on Trump's priority list. And then there are Senate confirmation hearings on any appointment.

Meanwhile we can expect to see more analysis in the coming weeks of what it all means for stem cells and regenerative medicine. 

California's Stem Cell Agency Smacks Stanford for Failing to Deliver on Financial Promises

The California stem cell agency today delivered an unusual and sharp rebuke to Stanford University, declaring that it needs to stand by its financial commitments to help back state-funded research. 

The message came during consideration of a request for more research cash from a Stanford researcher, Judith Shizuru. She sought $6 million for continuation of a clinical trial to develop a potentially "transformative" product that would eliminate the toxic impact of chemotherapy for a number of diseases. 

"It boggles my mind," said Jeff Sheehy, a member of the agency's governing board and chairman of its Science Committee, that Stanford, which has an endowment of $27 billion, has not stepped forward to provide the co-funding. 

The amount involved is $1.7 million and is due May 1. It is connected to an earlier $19 million award to Shizuru that kicked off her clinical trial. 

Sheehy noted that Stanford and its researchers have received $379 million from the agency since 2005. It is the top recipient of funds from the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. Stanford also has a member on CIRM's board. 

Steve Juelsgaard, chairman of the board's Finance Committee and a former top executive at Genentech, said that Stanford is "very well taken care of in terms of its economics." 

He said that the agency requires all institutions and businesses to sign agreements to deliver on promises of co-funding. CIRM cannot have two standards for its grantees, Juelsgaard said. 

Today was the first time that the $3 billion research agency has publicly rebuked a grantee on co-funding. Recipients of awards, be they institutions or individual researchers, are generally  treated tenderly in public.  (The full transcript of the meeting is available here.)

CIRM directors did not take issue with the quality of the research, which they described as good. Specifically, today's application sought to advance Shizuru's phase one clinical trial to develop a way to avoid the necessity of chemotherapy in a genetic affliction, popularly known as the bubble baby syndrome.

Nine researchers in the field sent letters to the CIRM board praising the work. Several called it "transformative" and said it could have use in afflictions ranging from blood cancer to diabetes. 

Shizuru applied for $6 million. However, the CIRM board reduced the award to $3.7 million and only on the condition that the previous co-funding be delivered.  

Shizuru told the CIRM board she accepted responsibility for raising the co-funding, which she said has been difficult. Board members noted that agreements on awards are signed by both the recipient researcher and his/her insitution. She said she would discuss today's action with Stanford officials.

Her application came before directors in January with a seal of approval from the agency's reviewers, who make their decisions behind closed doors. Normally, approval by reviewers means a rubber stamp by directors.

Action in January, however, was deferred until this month after directors raised questions about research delays and financial matters. The agency also publicly released a slough of information concerning Shizuru's work, most of which she provided to them.  

Here are links to key documents involving Shizuru application. 

• CIRM's news release on today's action
• CIRM's summary of reviewer comments on Shizuru's application, CLIN2-11431. The agency does not disclose the full application.
• CIRM staff's presentation today concerning the application
• Transcript of the January directors' meeting, including a relatively lengthy discussion and comments by Shizuru
• Today's meeting agenda, which includes links to the letters of support, most of them from prominent researchers in the field
• CIRM award details on the $19 million award, including three progress reports 
• Shizuru successful appeal letter on her 2012 application, which had a median score of 50 and was rejected by reviewers. 
• Clinicaltrials.gov information on Shizuru's clinical trial (start date and last update, both Nov. 15, 2016

(An early version of this item misspelled Shizuru's last name.)

A Peek Inside the California Stem Cell Research Machine: $25 Million, Babies, Bonds and Dwindling Cash

California's stem cell agency this week dished up rare public details of an advanced effort to create "transformative" therapies that would help cure afflictions ranging from diabetes to always fatal immune disorders.

The disclosure involves Stanford University researcher Judith Shizuru, severely ill babies, toxic chemical treatments, delays in clinical trials and stem cell agency board members who are acutely aware of the $3 billion agency's rapidly dwindling resources.

Judith Shizuru
Photo by Flynn Larsen, Ludwig Institute

All this plus more is on the table Thursday at a meeting of the directors of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. 

The agenda nominally contains one item, an application by Shizuru for $6 million from CIRM. But the issues reach back to 2013 and provide insight into difficult research pathways and how the agency manages its programs. 

At the top of the matter is the fact that the state agency expects to run out of cash for new awards by the end of this year. It is pinning its hopes on a proposed $5 billion bond measure on the November 2020 ballot.  Meanwhile, directors are trying to raise privately $200 million to tide it over until then. 

Avoiding Toxic Chemotherapy

That was the backdrop Wednesday Jan. 30 when directors convened to consider application number CLIN2-11431 by Shizuru for $6 million. She is seeking a way to avoid chemotherapy treatments and their toxic side effects in the case of a rare genetic affliction often referred to as the bubble baby syndrome. 

In December, CIRM's grant reviewers, meeting behind closed doors, approved Shizuru's application, an action that nearly invariably is rubber-stamped by directors. But last month was different, and a bit of CIRM history was brought up.

Shizuru received  a $19 million CIRM award in 2012 which has led to a phase one clinical trial with positive results for her therapy. Cost per each of the six patients so far averages $917,000, according to a CIRM document. 

However, additional patients are needed, along with more funding, before the potential product can reach the marketplace. The average cost of per patient will run about $333,333 during the final portion of the phase one trial.  Her latest application is aimed providing assistance with those costs. 

Questions about Delays and Co-Funding

Last month, questions arose among directors about months of delays in the clinical trial and a current shortfall in co-funding, among other things.

Steve Juelsgaard

Steve Juelsgaard, a former Genentech executive and chair of the directors' Finance Committee, said, 

"It's not clear to me that they're being frugal with the money that they have been given."

Juelsgaard also said,

"Delay doesn't necessarily add up to more money. They obviously spent the money on something that they didn't anticipate or under-budgeted or something. There's something more to it."

Another director, Jeff Sheehy, chair of the board's Science Committee, said,

"Financially, it seems very muddy to me."

Other directors weighed in as well, ultimately leading to a motion to delay action on the application to provide more time to find answers to questions.

At that point, Shizuru, who was in the audience, rose to respond.

"I understand CIRM's concerns, and I can see you're very thoughtful about how this money is being spent," she said, according to the transcript.

 The Sheehy-Shizuru Exchange

The Stanford researcher said that without additional funding the trial would have to suspend enrollment of additional patients, prompting this exchange between her and Sheehy.

"Shiruzu: Budgetarily we're better off using it (the remaining funding) to continue to follow the patients that we've already transplanted. From that budgetary standpoint, we should delay the trial. We should delay treating any more patients on the trial.

"Sheehy: So Stanford won't front you 1.6 million to (treat) patients if we don't give you the money today?

"Shiziru: I hesitate to say what they would do.

"Sheehy: To Stanford...they would actually put patients at risk?

"Shiziru: I'm not at liberty to say what Stanford would do."

Stanford is the No. 1 recipient of CIRM awards, chalking up $379 million over the past 14 years. It also has always had a member on the CIRM board of directors, who is not allowed to speak or vote on awards to Stanford.

Following Shizuru's comments, CIRM directors approved the motion to delay action until this week's meeting. Since the January session, Shizuru has provided the agency with more than five, single-spaced pages of explanation about her research, plus other material that has been kept under wraps for what CIRM has indicated are proprietary and legal reasons.

The information from Shizuru, as well as additional documents from CIRM, provided an unusual, public look into the agency's grant-making process as well as the hurdles encountered in advanced clinical research. In the past, reviews of applications approved by reviewers have received little or no discussion.

Shizuru's Perspective

In her material, which is available on the agenda for this week's meeting, Shiruzu said one, eight-month delay was caused by CIRM itself because of internal concerns. Another nine-month delay was caused by age-restrictions on patients.

"Significant delay" was also caused because of what might be called a supply and demand issue. The bubble baby syndrome is rare. Only one in out of 50,000 to 100,000 births results in a baby with the affliction: severe combined immunodeficiency.

Three other clinical trials are also competing for those rare patients. 

Nine letters of support were received by CIRM supporting the research, with some describing the potential result as "transformative." The letters also said Shizuru's approach could find use in a wide range of other afflictions, an expectation also agreed upon by CIRM. 

Shizuru said she is working on securing the needed co-funding for her first award, which is not yet concluded. As for commercialization, she said she and her colleagues have formed a company, whose name was not disclosed. She said she has a letter of support from one investor regarding "an intention to co-fund pending completion of due diligence."

In a final comment during the vote last month to delay consideration, one CIRM board member, a San Diego patient advocate for Parkinson's disease, praised the board's close examination of the application. David Higgins said, 

"I want to acknowledge fellow board members (for) their continued concern about spending taxpayer's money wisely because I think this is a great example of that."

(The public can listen to and participate in the Thursday meeting via the Internet. Instructions are on the meeting agenda.) 

California Stem Cell Agency Scores 50 Clinical Trials, Says It "Just Getting Started"

OAKLAND, Ca. -- California's ambitious stem cell agency this morning chalked up involvement in 50 clinical trials, an achievement that was regarded by some as unattainable 10 years ago.

The watershed event came when directors of the agency approved a $6.2 million proposal to help fight lymphoma.
Following the action, the first person ever to participate in a CIRM human embryonic stem cell trial, Richard Lajara, praised the efforts of the agency, which is running out of cash. 

He said the people of California have a responsibility to move forward with stem cell research and to continue to fund the agency. Lajara's appeal followed a statement from the agency that 35 persons are alive today because of clinical trials that it has helped to finance.

Lajara, who is paralyzed from the waist down, was enrolled in 2011 in the spinal injury trial initiated by Geron, Inc.,  and backed by the agency. 

Jonathan Thomas, chairman of the agency, which is formally called the California Institute for Regenerative Medicine(CIRM), said in a statement,

"We have come a long way in the past seven and a half years, helping advance the field from its early days to a much more mature space today, one capable of producing new treatments and even cures. 

 "But we feel that in many ways we are just getting started, and we intend funding as many additional clinical trials as we can for as long as we can."

In the early days of the agency, Robert Klein, its first chairman, and others widely regarded major participation in clinical trials, especially phase three, as largely beyond the financial capability of the agency. The cost was prohibitive, they said.

The cost of trials varies widely but can run into hundreds of millions of dollars, which could rapidly devour the $3 billion the agency had to spend, the reasoning went. Clinical trials are the last stage before a treatment is approved for widespread use by the federal government.

CIRM's first strategic plan in December 2006, which covered a 10 year period, anticipated some involvement in phase one and two trials. But it said,

"Because of their expense and because of the time required to reach this stage of clinical development, CIRM is unlikely to fund Phase III trials over the time span of the strategic plan."

The first patient to enroll in a CIRM clinical trial did not come until late 2011. 

Today, the agency has committed $541 million to clinical trials, including four that are in phase three, the ultimate trial hurdle to clear before a treatment wins approval. The phase three trials involve kidney disease and ALS.

The 14-year-old agency is now down to its last $144 million. Money for new awards will run out at the end of next year. CIRM is pinning its hopes for continued life on a proposed $5 billion ballot measure on the November 2020 ballot.

Key to winning approval would be a favorable result from its clinical trials -- one that would resonate with the voters. Their expectations were raised in 2004 by the ballot campaign that led to creation of the agency. However, the agency has yet to produce a stem cell treatment that is widely available.

California Stem Cell Agency Slated to Award $6.2 Million to Fight Lymphoma

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.

An FDA High Sign for a California Stem Cell Agency Bet: San Diego Biotech Business Earns FDA Speed-Up Approval

A San Diego firm backed by nearly $24 million from the California stem cell agency scored this week with a special designation from the federal government that could help speed approval of its therapy for a type of blood cancer. 

The firm is Poseida Therapeutics, Inc., which is testing the safety of a therapy for a type of blood cancer in a phase one clinical trial. 

The firm announced yesterday that the Food and Drug Administration (FDA) had granted Regenerative Medicine Advanced Therapy (RMAT) status for the adult stem cell-connected treatment. The designation is intended to expedite development of the multiple myeloma therapy. 

Eric Ostertag, CEO of the firm, said in a news release, that Poseida's potential treatment, P-BCMA-101, "is the first anti-BCMA CAR-T therapy to receive RMAT designation from the FDA and underscores the urgent need for new treatment options for multiple myeloma." 

He continued, 

“Initial Phase 1 data presented at the CAR-TCR Summit earlier this year included encouraging response rates and safety data, including meaningful responses in a heavily pretreated population...."

Ostertag said the firm expects to have more data by the end of the year. 

The stem cell agency, known formally as the California Institute for Regenerative Medicine (CIRM), has invested in 49 clinical trials. Five have garnered RMAT designation, which can significantly speed development of a commercial product. As of September, the FDA had granted only 24 RMAT designations nationally. 

Last Sepetember, Geoff Lomax, CIRM senior officer for medical affairs and strategic centers, wrote in cell&gene that the two-year-old, RMAT program streamlines therapy development by enabling possible priority FDA review and accelerated federal approval. 

Longitude Capital of Menlo Park, Ca., is a major investor in the firm, pumping in tens of millions of dollars.  

Major Sickle Cell Surge: Feds and California Collaborate on Cell Therapies for the Disease

In August, the stem cell agency staged a live event on Facebook dealing  with 

the current state of sickle cell research. It has since received  more than 2,200

 page views. Here is a link to the event, which featured  Don Kohn of  UCLA  and 

Mark Walters of UCSF Benioff Children’s Hospital. 

California's stem cell agency has embarked on what it calls a "remarkable" collaboration with the federal government aimed at developing cell-based and gene-based therapies for sickle cell disease, which affects 100,000 persons nationwide.

The partnership marks the first time that the state agency has partnered directly with the National Institutes of Health(NIH), which spend $100 million a year on sickle cell research. 

The NIH has committed an additional $7 million to jump start its new effort, dubbed "The Cure Sickle Cell Initiative."   The California stem cell agency has already pumped nearly $39 million into sickle cell research. 

The affliction is caused by a genetic defect that deprives the body of oxygen, "wreaks havoc on the body, damaging organs, causing severe pain, and potentially leading to premature death," says the NIH. 

In the agreement (see below) with California's $3 billion stem cell agency, the NIH said that the agency is "a recognized leader in the development and funding of clinical trials focused on cell-based therapies and is now working to accelerate support for clinical stage candidate treatments that demonstrate scientific excellence."

Millan told directors in in June that the arrangement amounted to a "quite remarkable" recognition of CIRM's capabilities. She said the NIH "made a decision that they needed to partner with us in order to have the best shot at accomplishing what they want to do with this 'cure sickle cell initiative.'"

On Thursday, directors of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, will receive a more complete briefing about the full range of CIRM's involvement.

CIRM will handle the funding processes for the applications for the late stage research program, making funding decisions in as little as 85 days. The agency's work will include scientific peer review, contracting and post-award management, according to CIRM documents. (The documents are part of the presentation that can be found here.)

Millan said that the NIH has recognized the agency's value in terms of accelerating development therapies, building late development research and translating basic research into clinical use. 

The agency said it will provide funding on approved awards for work done in California, according to CIRM rules. It will have the ability, in consultation with the NIH,  to suspend or terminate research if milestones are missed, including taking back unused funds. Kevin McCormack, a spokesman for the agency, said that it will be compensated by the NIH for additional work that it has to perform but that details are yet to be worked out.. 

Last month, the NIH said in a news release:

"Currently, the only cure for sickle cell disease is a bone marrow transplant, a procedure in which a sick patient receives bone marrow from a healthy, genetically-compatible sibling donor. However, transplants are too risky for many adults, and only about 18 percent of children with sickle cell disease have a healthy, matched sibling donor.

"The Cure Sickle Cell Initiative seeks to develop cures for a far broader group of individuals with the disease, and it is initially focusing on gene therapies that modify the patient’s own hematopoietic stem cells (HSCs), which make red and other blood cells. These modified HSCs can then be given back to the patient via a bone marrow transplant, making a cure available to more patients who lack a matched donor."

Below is a CIRM video on sickle cell disease and a copy of the agreement between the stem cell agency and the NIH. 

(Editor's note: An earlier version of this item incorrectly reported that the agency had committed more than $200 million to sickle cell research, based on inaccurate figures on the CIRM web site. The correct amount is $38,8 million. CIRM said the error was created by a computer glitch and that it has corrected the figures on its site.)

Sickle Cell Cirm-nhlbi Mou ... by on Scribd

$10 Million More for Viacyte for a Virtual Stem Cell Cure for Type 1 Diabetes

The San Diego stem cell company that has snagged $72 million from the state of California  announced this week another $10 million infusion from the firm that created the rain gear fabric known as Gore-Tex.

The San Diego firm is Viacyte, Inc., a privately held company that has received more than any other company from the $3 billion California stem cell agency. In 2017, Viacyte became involved with W.L. Gore & Associates, Inc., a materials science company that deals with drug delivery technologies.

Gore is also the enterprise whose Gore-Tex product has shaped the current outerwear industry.

On Tuesday, Viacyte announced the $10 million investment by Gore. The funds are coming in the form of a convertible promissory note.

Paul Laikind, president of Viacyte, said this week that the collaboration with Gore "has been exceptionally productive." He said the use of Gore membranes "has proven invaluable for improving the performance of the PEC-Encap product candidate in non-clinical studies that have been shown to be reflective of the human experience."

He said the additional support "should allow us to resume clinical testing of PEC-Encap as early as the first half of 2019."

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."

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."

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.")

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

Pawash Kashyap and son, Ronnie

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.

"It was a blessing day for us," said Pawash Kashyap, who appeared before the Assembly Select Committee on Biotechnology,  which held a hearing Aug. 15 dealing with the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. Kashyab referred to the occasion when he and his wife, Upasana, received a call from UC San Francisco warning him of the immune deficiency that afflicted their baby, Ronnie.

Researchers told them that the child could well die if he suffered from even a slight infection. The immune deficiency is sometimes known as the "bubble baby" disease, which has sometimes meant children were encased in plastic bubbles to stave off infections.

The problem was detected by routine newborn screening. Kashyap told legislators of their concern after learning the bad news.

"We Googled it, and nothing good was coming out of it."

Ultimately, the Ronnie was treated successfully. His father said that Ronnie has experienced potentially infectious crowds in malls and elsewhere and that he is doing "fantastically well."

Ronnie is now the "cover baby" on CIRM's annual report, which was praised by one lawmaker, Assemblyman Todd Gloria, D-San Diego. He said the report told the nearly 14-year, CIRM story in understandable and compelling language.

The full hearing can be seen here and downloaded. Kashyap's brief remarks begin at 55:36 into the video (he spoke without a prepared text). An audio file is also available at the same URL.

Here are links to the remarks at the hearing by CIRM CEO Maria Millan, CIRM Vice Chair Art Torres, patient advocate Don Reed, Jan Nolta, head of the UC Davis stem cell program, and David Jensen, publisher of this web site.