San Francisco Business Times: Risky Downside to California's $75 Million Stem Cell Venture Plan

The stem cell agency plan is dubbed ATP3. Here is some of the criteria.

California’s $75 million, stem-cell dip into venture capital waters poses an “embarrassing risk,” according to a story in the San Francisco Business Times.

The article by by Ron Leuty said,

“The strategy offers a potential high return for CIRM and the stem cell field in general, and it's not without the classic scientific risk of biotech investing. But it holds a larger, potentially more damaging and embarrassing risk as well if applicants peruse CIRM's shelves but find nothing to buy after the agency has invested hundreds of millions of taxpayer cash.”

Leuty wrote yesterday about the agency’s proposed plan, first reported last week by the California Stem Cell Report. The agency plans to entice -- with $75 million -- Big Pharma or other investors into a partnership. The private partner would also have to pony up $75 million. The combined enterprise would have first pick of the best of CIRM’s unpartnered research.

Leuty wrote,

"'The plan is not without risk, no doubt about that,' said CIRM President and CEO Randy Mills. 'Nothing about this plan is attempting to do something easy or easily achievable. This is hard and requires a lot of effort, but if we're successful the outcome of it should be transformative to CIRM and regenerative medicine.'”

Leuty continued,

“But there's a potential downside as well if nobody shows up to window shop at CIRM, much less to buy, because stem cell therapies are largely unproven, said Andy Schwab, a managing partner at Menlo Park venture capital firm 5AM Ventures.

"’The mechanism of action still is unknown. It's not like gene editing and gene therapy, where it's very specific,’ said Schwab, mentioning two of the hottest areas of medical science and investment action. ‘It's tough when you don't know the mechanism of action.’

“CIRM also hasn't invested in areas around white-hot CAR-T therapies, where chimeric antigen receptors on the surface of immune system T cells are genetically engineered to amp up their recognition and ability to kill cancer cells.

"’CIRM has really missed it,’ Schwab said. ‘They haven't been leaders in the right space.'

“Still, Schwab said, CIRM does have plenty of ‘really interesting research’ in its portfolio that could interest an investor. The issue, he added, is whether science projects can be commercially viable in a short timeframe.”

Luety continued,

"’It's an innovative solution to what they've been trying to do — to rush basic research concepts into actual treatments that meet people's medical needs,’ said John Simpson, an advocate and former stem cell project director with Consumer Watchdog, a Santa Monica nonprofit that for years tracked CIRM policies and spending.

"’There are potential pitfalls if (the spinout) goes to somebody's buddies,’ Simpson said. ‘But as long as the board does its job and closely vets the awards, this could have some real payback.’"

Responding to a query today from the California Stem Cell Report, Kevin McCormack, senior director for CIRM communications, said that "under CIRM’s IP (intellectual property) regulations, a company that licenses CIRM projects and commercializes them would owe a royalty to the general fund of the State of California(not CIRM). However, we are contemplating awarding funds to the successful ATP3 applicant as a loan, and under Proposition 71, the proceeds of a loan are paid to CIRM for the purposes of making additional research awards. So it is possible that, in addition to the royalties it would owe the general fund as a result of licensing and commercializing CIRM projects, the successful awardee may also owe money to CIRM. "

The $75 million proposal comes up for ratification by the agency board next Thursday at a meeting in Los Angeles.

(Editor's note: The paragraph in this item dealing with IP was inserted shortly after the original version of this item was posted.)

Stem Cell Cures: Who is Going to Pay?

Money and the FDA were on the agenda today over at The Stem Cellar.

The Cellar is the blog of the $3 billion California stem cell agency, whose minions were on the scene in Atlanta for the World Stem Cell Summit.

Kevin McCormack, the agency’s senior director for communications, wrote about the FDA, only a couple of weeks after the agency took on the FDA for slowness and excessive caution. Don Gibbons, who also works in communications for the agency, wrote about the minor matter of money -- just who is going to pay for stem cell therapies.

First, the money bit, since as Gibbons points out,

“The bottom line: stem cell therapies will never be widely available if insurers won’t pay for them”

Gibbons wrote about a panel dealing with that dubious euphemism -- “reimbursement:”

“Elizabeth Powers of the IMS Consulting group suggested the audience pay close attention to the cancer market.  She said insurers and other payers of health care services are tired of paying for ‘statistically significant’ improvements in survival that only translate to a few weeks on average. She said payers are moving away from just whether a new therapy is different from prior therapies and want to be shown true value.”

Use of the word “reimbursement” is Big Pharma’s way of NOT saying that profits must be made if treatments are going to be produced. Unfortunately, the use of the term ill serves the industry by creating the impression among the public that they are being hornswoggled with jargon. The word smacks of entitlement, as if someone should guarantee the drug companies billion-dollar earnings.

McCormack focused on what he called a “clarion call” by Robert Califf, the deputy commissioner for the Food and Drug Administration (FDA), who has been with the FDA only eight months. Califf called for deeper patient involvement in drug development decisions.

McCormack also wrote,

“(Califf) says the first goal of the FDA has to be to protect the public, and that it’s hard to balance safety and innovation. ‘That’s an issue we struggle with every day.’”

McCormack did not link to the strong language concerning the FDA found in his agency’s new plan for spending $900 million over the next few years in search of a stem cell therapy.

Underlying both pieces on The Stem Cellar are two issues for the CIRM board to consider next week as it eyes the future. Does the agency, which will cost the California public roughly $6 billion including interest, want to fund research that is likely to lead to enormously expensive treatments that insurers and the federal government (via Medicare and Medicaid) will be reluctant and even refuse to pay for.

The usual argument is that prices will ultimately come down. However, we have already seen strong evidence to the contrary. The concerns have risen to the level of presidential politics and are not likely to vanish, regardless of the hopeful expectations of industry.

As for the FDA, when safety is the all-pervasive driving force of the FDA, it naturally will lead to slower action and caution on new treatments.  California’s stem cell agency, however, is looking for significant results in the next five years. Its money is running out. Cash for new awards will vanish in 2020. And the possibility of raising significant new funds is bleak if the agency cannot show major results after what will be 16 years of effort.

Shameless Family Promotion: World's Best Leather iPhone Case

Looking for a terrific iPhone case with room for cash and cards as well? Look no further. 

The case comes in in different shades. Saddle black here.

You can find it at coveredplanet.com. The case is called The Traveler and is "the world's best leather iPhone wallet case." It provides "easy convenience and rugged protection" for people looking for more than the usual plastic. In other words, a perfect holiday gift.

But first a disclosure: Coveredplanet is an enterprise run by this writer's son out of Santa Barbara. He devised the case initially as a personal solution, inspired by the old days of cattle ranches, vaqueros and saddle-making on the California coast.

Coveredplanet says the case is "handcrafted here in the USA by some of world's best leather craftsmen, and we use only the highest quality materials - saddle grade leather, sturdy parachute thread, black matte finished polycarbonate cases and brass plated rivets - in our products. If you're not 100% satisfied, we also provide a 30-day return policy for your leather iPhone wallet case, but, we think, you'll never want to give it back."

Please check it out.  A 20 percent discount is available until Dec. 15. Type in FAF20 when ordering.

California Stem Cell Agency: FDA Stalling Development of Stem Cell Cures

The FDA is one of the favorite whipping boys in Washington, D.C., but it is not often that a state governmental agency also decides to thrash the body that is charged with assuring the safety of the nation’s drugs and medical treatments.

California’s $3 billion stem cell agency, however, is doing just that. As part of its new plan for spending its last $900 million, the agency is lambasting the FDA for standing in the way of speedy development of stem cell therapies.

The general chorus about the failings of the FDA is large. This morning a Google search on the term “FDA whipping boy” turned up 155,000 results. A search on the term “criticism FDA approval process” produced 569,000 results including an entire Wikipedia entry. Of course, not everyone agrees that the FDA is too stringent in its drug regulation. (See here and here.)

It should also be noted that stem cell therapies provide novel challenges, much more so than conventional, new drug offerings.

Nonetheless, here is the text of what the California Institute for Regenerative Medicine had to say about FDA in its new strategic plan, which is expected to be approved Dec. 17 in Los Angeles.

“FDA Challenges and Obstacles

“We heard a resounding chorus frommost stakeholders of the enormouschallenges with the regulatory burdensplaced on cell therapy in general, andstem cell therapy even more so, by theFDA. Instead of the ever growing bodyof work in cell therapy, with its overallexcellent safety record, making thepathway to approval smoother, it seemsto many that the requirements imposedby the FDA are increasing.

“A recent therapy touted by the FDAas a success had such a high clinicaldevelopment burden placed on it thatby the time it was finally approved,standard of care had evolved andits market was significantly reduced,leading to liquidation of the company.Companies, and sadly patients, mustgo outside the United States, as faraway as Japan, to find regulatoryagencies willing to work successfullytowards approval.

“Ultra-orphan diseases still must reachthe same statistical burden, whichrequires larger effect sizes than seenin the majority of approved, successfuldrugs and biologics. Everyone hastheir own list of how the FDA makesit seemingly impossible to take stemcell therapy through the regulatoryprocess. In 2014, Japan recognizedthe differences in regulatory approachesneeded for regenerative medicine andtook action. However, the FDA does notappear to have the same motivation. Infact, in a disturbing turn of events, FDAhas recently began providing certainmembers of the U.S. Congress withcompletely one-sided information on thedangers of cell therapies encounteredin clinical trials. However, FDA failedto provided any context or balancedinformation regarding the safety recordof cell therapies that comprises the vastmajority published clinical literature. TheFDA appears to be literally lobbyingagainst the very therapeutic modalitythey are responsible for promoting.

“CIRM needs to join with Congress,academia, and patients, to bring aboutreal change to meaningfully balancerisk-benefit in FDA regulations andmore importantly, the FDA’s behaviorand willingness to grant licensure toeffective therapies.”

Attacking Barriers to Stem Cell Cures: California to Put Official Stamp on New Strategy

Call it California’s $900-million road map to a stem cell cure. 

That’s what up for final action next week by the governing board of the state’s $3 billion stem cell agency, officially known as the California Institute for Regenerative Medicine (CIRM).

The plan includes a $105 million lure to entice Big Pharma and other possible investors to join the Golden State’s regenerative medicine bandwagon and create an “industrial stem cell therapeutic powerhouse.” 

Randy Mills, president of the California stem cell agency, and his team are calling for “attacks” on barriers to clinical development of therapies. That includes the FDA which Mills and company say “appears to be literally lobbying against the very therapeutic modality they are responsible for promoting.” (See here and here.)

The key part of the $105 million stem surge would bring together next year the state of California and private investors in a joint enterprise. Under the plan, the private investors would have the pick of the best research from CIRM that has not already attracted partners.

The agency would pony up $75 million with another $75 million coming from investors.

(Here are links to the CIRM description of the three components of the $105 million effort: here, here and here.)

The agenda for the Dec. 17 meeting in Los Angeles includes other matters, such as action on a clinical research applications for millions of dollars. The review summaries of those applications are not yet available online, but most of the additional supporting material for the meeting has been posted. That is a healthy change from some recent past meetings where backup information has been missing until much too late.

(The morning of Wednesday Dec. 9, the agency posted a note on the agenda saying the applications were no longer under consideration. Often that means that the proposals have been withdrawn because of negative recommendations from reviewers.)

Also on tap is a major change in the scoring of applications in non-clinical programs. Here is how the change is described by a CIRM memo:

“For non-Clinical Program applications, therefore, we propose to revert to our former scoring system (1 to 100) with two tiers: (Tier 1) average score of 85 or above, recommended for funding, if funds are available, and (Tier 2) average score of 84 or below, not recommended for funding. In  addition, for those programs for which only one application is expected to be funded, we propose to specify that the application that receives the highest average scientific score shall be deemed to be the GWG’s recommendation for funding.”

These changes would be in effect for the three rounds involved in the $105 million surge.

The board is also being asked to raise the cap on payments to patient advocate members of the board from $15,000 to $30,000 annually. The move would be retroactive to the beginning of this year. 

A CIRM memo said that demands on patient advocate directors have increased dramatically both in terms of the numbers of meetings and their role. The memo said that prior to Mills’ arrival at CIRM patient advocates were involved in only three or four review sessions a year. In 2015, those sessions have already risen to close to a dozen.

While next week’s meeting will be based in Los Angeles, remote, telephonic locations where the public can participate will be located at Stanford and UC San Diego. Specific addresses can be found on the agenda.

California's New $105 Million Stem Cell Surge: The Creation of an Industrial Powerhouse

Highlights

National biotech interest likely

$75 million alone for public-private effort

High risk, high reward

More support for Alpha clinics

California is hoping to fire up the state’s stem cell industry this month with $105 million aimed at creation of an unprecedented, “industrial stem cell therapeutic powerhouse” on the nation’s West Coast. 

The money is coming from the state’s stem cell agency, which has already spent $2 billion on stem cell research in the last decade. The agency is now on its last $900 million and pushing hard to translate stem cells into therapies and cures. It is expected to run out of money for new awards in 2020.

Earlier this week, a key panel of the agency’s governing board approved the $105 million surge, a decision that is certain to be ratified by the full board at a meeting Dec. 17 in Los Angeles. The action will initiate a 2016 competition for the cash, which is likely to draw national interest, although the money can be spent only within the state.

The largest component of the $105 million is $75 million for a program that the agency has dubbed the “Accelerating Therapies through Public-Private Partnership” or ATP3. The award would be one of the largest ever made by the agency, which is formally known as the California Institute for Regenerative Medicine (CIRM).

Also approved was a $15 million round for an "accelerating center" and another $15 million round for a "translating center." All of the awards are scheduled to be made by late 2016. 

Under the ATP3 public-private round, the recipient would be required to match the $75 million from California taxpayers. The program would bundle together for continued CIRM funding the most promising current CIRM projects. Those projects -- a “portfolio of  ‘high risk’ but high reward projects” -- would be selected by the recipient for development for commercialization, the agency said in a memo.

CIRM’s plan for the project said,

“The aggregation of a basket of otherwise unpartnered CIRM projects offers the successful applicant ‘multiple shots on goal.’ This increases the probability of successfully developing and commercializing a stem cell treatment and makes significant industry investment in stem cell technology more attractive.”

The agency said in a presentation that industry is “beginning to show interest” in stem cell therapies but only 8 percent of CIRM’s 71 active therapeutic programs have industry partners.

CIRM’s presentation said the awardee must have a “top-tier” track record and “could be an established company, a spin-off or a new company with a team formed by Pharma, biotechnology or by an investor.”

CIRM said Californians would benefit from "creation of an industrial stem cell therapeutic powerhouse that increases the likelihood of the commercialization of stem cell treatments for patients with unmet medical needs."

The other CIRM award rounds that are up for ratification later this month aim also at bringing stem cell therapies into widespread use.

The $15 million accelerating center round, which is open to non-California-based organizations, would fund the following activities:

• “Regulatory management services (including IND preparation and submission)
• “Clinical trial planning and management, including site selection, contracting, and clinical site management (e.g., patient recruitment and operational and logistical support)
• “ Data management, biostatical and analytical services
• “Provision of services to (CIRM’s) Alpha Clinics Network, CIRM-funded investigators and sponsors with translational and clinical stage projects, and clinical sites seeking to join the Alpha Clinics Network”

The translating center would fund the following activities:

• “Project planning in coordination with CIRM and the Accelerating Center.
• “Project management for pre-clinical IND-enabling development programs, including pivotal pharmacology and toxicology studies.
• “Process development and product manufacturing activities suitable for production of cell products under good manufacturing practices (GMP).
• “Assembly and authorship of documents to support IND submissions and FDA interactions.
• “Development and execution of a business plan to sustain operations beyond CIRM funding.”

Less Than $1 Billion Left: California Stem Cell Agency Lays Out its Five-Year Bucket List

CIRM's spending plans by area -- CIRM graphic

Highlights

Three pages on risk of research

Funding ends in 2020

Two new centers proposed, up to $15 million each

Clear pathways to commercialization

The California stem cell agency today unveiled its plan for spending its last $900 million, calling for 50 new clinical trials and an increasingly hard-eyed focus on turning earlier stage research into therapies.

Between now and 2020, the agency’s strategic plan budgeted $620 million for clinical and translational research compared to $170 million for more basic efforts.   

The proposal builds on “radical” changes already underway at the agency and is not without risk. Indeed, the 45-page page plan devotes three pages to the subject of “risk.” Sherry Lansing, a longtime board member and former chair of the University of California regents, said in a press release,

“It’s an ambitious plan, but you never achieve anything worthwhile by playing it safe.”

Jonathan Thomas, chair of the agency’s governing board, said the strategic plan “began with us throwing out all our preconceived notions of what we do, and instead focused on what was possible with the time and money we have left.”

The California Institute for Regenerative Medicine (CIRM), as the $3 billion agency is formally known, is projected to run out of funds for new awards in 2020. It is unclear what if any cash can be raised from either public or private sources. However, Thomas is scheduled to discuss future funding prospects at the board’s Dec. 17 meeting in Los Angeles.

Much of the plan has been revealed in the past six months as Randy Mills, CEO of CIRM, briefed the governing board on its developing direction. Mills joined the agency in May 2014 after a career in the biotech business. The thrust of the strategic plan reflects his business background and a strong emphasis on measurable benchmarks and organizational clarity.  He launched an effort called CIRM 2.0 earlier this year in an effort to speed funds to clinical efforts and improve the quality of applications. (See here and here for earlier stories on the strategic plan.)

New to the spending plan -- at least in any kind of detail -- were two proposals slated for $12 million to $15 million each. One was dubbed a “translating center.” The other was called an “accelerating center.”

The translating center will be located at a single enterprise and be charged with development of cGMP compliant cell manufacturing processes, providing “core services” leading to FDA investigational new drug applications and coordinating with the FDA and the accelerating center.

The accelerating center will also be located a single enterprise that has stem cell-specific regulatory expertise. It will provide support for clinical trials in an effort to accelerate the regulatory process and conduct of clinical trials.

Over the past six months or so, Mill has repeatedly made the case for capturing promising early research and ensuring that it has a clear pathway to clinical trials and ultimately into the market.  

Under his strategic plan, “every program will be integrated into and coordinated with the overall effort” to fulfill the CIRM mission: “To accelerate stem cell therapies to patients with unmet needs.”

The plan additionally sets concrete standards for measuring the agency’s performance as well as each team’s performance within the agency, including such specifics as the percent of application reviews held as scheduled and percent of projects that advance to the next stage.

The proposal is set for discussion and action at the directors’ Science Subcommittee meeting next Monday and goes to the full board on Dec. 17 for final approval. The meeting will be based at CIRM's new headquarters in Oakland with remote, teleconference locations for the public in San Diego and Los Angeles. Specific addresses are on the agenda.

While the plan is called a draft, it is not likely to undergo significant changes. However, interested parties can weigh in with comments by emailing them to CIRM at this email address kmccormack@cirm.ca.gov by 5 p.m. Dec. 3.

CIRM's goals for the next five years -- CIRM graphic

Inside the Story of Cesca Therapeutics, the California Stem Cell Agency and its Kibosh of an $11 Million Proposal

The Sacramento Bee today carried a story taking a longer look at Cesca Therapeutics, Inc., its travails with the California stem agency and the firm’s application for $11 million to help finance a phase three clinical trial.

The freelance article was written by the publisher of this blog, David Jensen. Here is the full text of the story.

  Rancho Cordova firm comes up empty in bid to win $11 million from stem cell agency _ The Sacramento Bee

Cesca Stock Plunges 50 Percent in Wake of California Stem Cell Agency News

The stock price of Cesca Therapeutics yesterday plummeted about 50 percent after it reported bad news about its application for $10 million from the California stem cell agency.

The stock closed at 30 cents a share in relatively heavy trading, compared to its close of 59 cents the previous day. Over the last 52 weeks, the stock has ranged from 29 cents to $1.24.

On Monday, the company, which is based in the Sacramento suburb of Rancho Cordova, announced that it had withdrawn its application from the $3 billion state-funded agency until it assessed critical reviewer comments. Cesca’s proposal involves a roughly $20 million, phase three clinical trial to test a product aimed at critical limb ischemia.

The firm had raised financing for the trial that was contingent on CIRM approval of a grant.  

In its Monday press release, company president Robin Stracey said,

“We expect to spend the next several weeks re-validating and/or amending select elements of our plan, with a particular focus on the anticipated rate of patient enrollment, the overall timetable and the design of the statistical plan. Having said that, we remain very excited by the prospects for our program.”

California to Nix $6.8 Million for Parkinson's Research, Flawed Proposal Cited

Directors of the California stem cell agency are scheduled to meet Thursday to reject a $6.8 million application to finance late stage research to develop a therapy for Parkinson’s Disease.

Twelve of the agency’s blue-ribbon, scientific reviewers last month voted unanimously against the proposal, declaring it was “flawed” and should not be resubmitted to the agency. Directors of the agency almost never overturn negative decisions of its reviewers.

This week’s meeting focuses unusual attention on the application. It is the only one scheduled to be considered at the meeting, which is part of the fast-track funding efforts this year by the stem cell agency. In the past, final approval or rejection of applications usually involved a number of applications. Reviewers’ decisions against funding have been rubber-stamped with no discussion. Scores on the rejected applications were not disclosed.

One of the goals of the agency’s “CIRM 2.0” effort, in addition to speeding funding, is to improve grant applications. It may well be that the agency is attempting to reinforce, via the application review summary, its message to researchers to step up the quality of their proposals for millions of dollars in taxpayer support.

The review summary found considerable fault with the rationale of the proposal. It said the data presented was “insufficient.” The dosage involved was “not clearly described.” Timelines may be “unrealistic,” the document declared.

The summary also said,

“It is not clear whether the focus of the applicant is an embryonic (ESC) or induced pluripotent stem cell (iPSC) derived product.”

“Reviewers....encouraged the (applicant) team to carefully consider feedback in any earlier stage application.”

The name of the applicant was not disclosed in keeping with the agency’s longstanding practice of withholding such information. Responding to a question, an agency spokesman said the application came from an academic institution. One Parkinson’s researcher who has been mentioned in the news in recent months, Jeanne Loring of Scripps, told the California Stem Cell Report that the application did not involve her. 

The rejection would be only the second in the CIRM 2.0 program, according to Kevin McCormack, senior director of communications for the agency. 

The public can weigh in on any subject during Thursday's meeting at teleconference sites in Beverly Hills, San Diego, South San Francisco, Napa, Irvine,, Los Gatos, Elk Grove, Redwood City, San Francisco and two in Sacramento. Specific addresses can be found on the agenda.