The California Stem Cell Report is going dark for the holidays and will resume during the first week of January 2016, a year that also will bring us the Chinese year of the red fire monkey."Fujifilm believes regenerative medicine (using stem cells to treat diseases) will be a $50 billion market by 2025. Manufacturing will have to ramp up with it. We will have to look at leveraging other technologies to scale the business.
"The concept is that some day, we’ll each have our own iPS cells made and banked. So that when you need heart cells after a heart attack or you have eye damage from age-related macular degeneration, you pull your own cells out of the stem cell bank. Or you can use them to test drugs for toxicity before you take them.
"We’re envisioning replacing existing cells that will stay in the body and not be sloughed off later."
"We have a very aggressive target: 60 percent growth in revenue each year, for the next five years. We want our cells to be used for drug research and screening and for cell therapy — treating diseases."Parker said,
"CDI already has three cell therapy programs going — for age-related macular degeneration; Parkinson’s disease; and to replace scarred heart muscle after a heart attack — all using our iPS-derived cells. We anticipate being profitable by the end of 2017.
"CDI has 160 employees, about 120 of them in Madison. We expect to hire another 15 to 20 by the end of 2016, at least 10 of them in Madison.Hirao said,
"We are trying to change the model. Current drug testing is performed, mostly, using animal cells. By 2019, we want the majority of drug testing to use iPS cells instead.
"Once the market is created, there will be a big jump in sales. That’s why Fujijilm has great expectations for this."
"The poet T. S. Eliot once wrote: 'If you aren’t in over your head, how do you know how tall you are?' Well, everyone at CIRM, California’s stem cell institute, is about to find out how tall we are."Here are links to the other pieces: The Bee (written by yours truly), the San Diego Union-Tribune, Southern California public radio (Stephanie O'Neill did two stories, see here and here) and California Healthline. The Bee piece may get picked up the other Bee newspapers in Fresno and Modesto.
“It’s ambitious, but then isn’t that what the people of California were when they approved Proposition 71. They wanted to create something that was going to change the face of medicine. That’s what we hope to do….”
“There are risks inherent in the development of new, disruptive technology. The bigger risk is failing to deliver on their underlying promise to bring new regenerative therapies to patients…. The bigger risk is not doing anything.”
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| Look at the status of CIRM funding by disease |
“The $30 million is to help ensure that we have funds to cover the administration of all the awards we make in the next five years. As you know those are multi-year awards so if we can continue making new awards till, say, 2020 we also want to make sure we have enough money in our admin bucket (which is separate fro the research bucket) to cover the supervision and support for those awards.
“We are also but separately working on finding other sources of funding so the agency as a whole can continue funding and administering research after our current money runs out , but that is a separate task.”Presentation documents posted online made reference to public funding, but had no specifics. Currently the agency survives on money borrowed by the state under the terms of the ballot initiative that created the research program in 2004. However, that $3 billion source is shrinking, and the agency is down to its last $890 million. The online documents made no mention of plans to continue with new awards or loans beyond 2020. Jonathan Thomas, agency chairman, is expected to provide more details tomorrow to the board on the financing plan.
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| Bill Bowes, UCSB photo |
“These gifts are contingent upon CIRM raising an additional $23 million before June 30, 2019 and not having access to additional funds for its administrative costs.”
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| Randy Mills, MCC photo |
“We have had the current FDA regulatory structure for cell therapy in place for 15 years, and in that 15 years not one stem cell therapy has been approved. The scoreboard is not lying, there’s a zero on it. Not one therapy has been approved. There is an issue here, we can’t ignore that fact and so we made it part of our proposed new Strategic Plan to try and remove this burden.
“There is an excessively long translational pathway to get an Investigational New Drug (IND) approval from the FDA (a necessary step to proceed with testing a therapy in a clinical trial). For non-cell therapies it takes 3-4 years to get an IND. For cell therapies it takes 6-8 years, twice as long.”
“We are not anti-regulation, we are not anti-FDA, and we are not calling for the removal of rules and regulations around stem cell therapies, that would be bad for patients and research. These therapies have risks and we are not proposing any strategy that puts things on the market without any testing or safety data. But right now we are being so careful about safety to ensure patients are not put at risk while those same patients are dying from their disease.”
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| Bob Klein, Elie Dolgin photo |
"Stanford University, Memorial Sloan Kettering Cancer Center, and other prestigious medical research institutions have flagrantly violated a federal law requiring public reporting of study results, depriving patients and doctors of complete data to gauge the safety and benefits of treatments, a STAT investigation has found.
"The violations have left gaping holes in a federal database used by millions of patients, their relatives, and medical professionals, often to compare the effectiveness and side effects of treatments for deadly diseases such as advanced breast cancer
"The worst offenders included four of the top 10 recipients of federal medical research funding from the National Institutes of Health: Stanford, the University of Pennsylvania, the University of Pittsburgh, and the University of California, San Diego. All disclosed research results late or not at all at least 95 percent of the time since reporting became mandatory in 2008."Francis Collins, head of the NIH, said he finds the failure to report "very troubling."
“If all goes according to plan, doctors will implant replacement brain cells into 12 Parkinson’s patients, probably in the first quarter of 2016, said Russell Kern, the company’s chief scientific officer. These are called neural precursor cells, a slightly immature kind of neuron. The cells will finish maturing in the brain into the kind of neurons destroyed by the movement disorder.
“The neural precursor cells are derived from the company’s parthenogenetic stem cells, which are produced from unfertilized human egg cells.”International Stem Cell is a publicly traded firm whose researchers pitched proposals with some regularity to the stem cell agency a few years back. It was not known whether any of the applications involved the Parkinson's therapy. The firm’s personnel also attended CIRM board meetings with some frequency. (For earlier items on the company, see here, here, here, here and here.)
“That’s also the approach Summit for Stem Cell will take, said stem cell scientist Jeanne Loring, a leader of the Summit for Stem Cell project. The cells make proper connections with the brain better when they are still maturing, said Loring, who’s also head of the regenerative medicine program at The Scripps Research Institute in La Jolla.”
“Loring said she views ISCO as a partner in fighting Parkinson’s. One of her former students is working for the company, she said….
“ISCO’s choice of Australia for its streamlined regulatory process makes sense, Loring said. Her team, with U.S.-based academics and medical professionals, doesn’t have the same flexibility as ISCO in looking for clinical trial locations, she said.”
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| The stem cell agency plan is dubbed ATP3. Here is some of the criteria. |
“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.
"'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 bottom line: stem cell therapies will never be widely available if insurers won’t pay for them”
“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.”
“(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.’”
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The case comes in in different shades. Saddle black here. |
“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.”
