Friday, October 19, 2018

Autism to Bladder Cancer: California Awards $25.2 Million For Stem Cell Research

The California stem cell agency yesterday approved $25.2 million for research involving a spate of diseases, ranging from HIV and autism to hearing loss and bladder cancer.

The only application involving clinical stage work was submitted by Xiuli Wang of the City of Hope in Duarte, Ca., for her research on a CAR-T treatment to achieve a functional cure for HIV infection without the need for antiretroviral drug therapy.

The application (CLIN1-11223) sought $3.8 million to take her proposed therapy to the point where it can win approval to begin clinical trials. Here is a link to the summary of the review of her application. 

Directors of the California Institute for Regenerative Medicine(CIRM), as the agency is formally known, also approved $13.5 million in awards to translate basic research into clinical work and $7.9 million for more basic research. 

Here is a list of the principal investigators in the translation round. Summaries of the reviews can be found in this document. Translation refers to research that is moving from the basic stage to clinical.

  • Steven Schwartz of UCLA, $5.1 million, TRAN1-11265, clinical translation of autologous regenerative cell therapy for blindness
  • Karin Gaensler of UCSF, $4.2 million, TRAN1-11259, development of engineered autologous leukemia vaccines to target residual leukemic stem cells
  • Ted Leng of Stanford, also $4.2 million, TRAN1-11300, a purified allogeneic cell therapy product for treatment of dry age-related macular degeneration
Here is a list of awards whose approval was stalled in July for financial reasons. The review summaries with scores can be found in this document.

  • Tracy Grikscheit of Children's Hospital Los Angeles, $1.3 million, DISC2-10979, Universal Pluripotent Liver Failure Therapy (UPLiFT)
  • Philip Beachy of Stanford, $1.4 million, DISC2-11105, pluripotent stem cell-derived bladder epithelialprogenitors for definitive cell replacement therapy of bladder cancer
  • Jonathan Lin of UC San Diego, DISC2-10973, $1.2 million, small molecule proteostasis regulators to treat photoreceptor diseases
  • Stuart Lipton of Scripps, DISC2-11070, $1.8 million, drug development for autism spectrum disorder
  • Neil Segil of USC, DISC2-11183, $833,971, A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs
  • Alan Cheng of Stanford, DISC2-11199, $1.4 million, modulation of the Wnt pathway to restore inner ear function
Sphere: Related Content

Thursday, October 18, 2018

$144 Million California Stem Cell Research Program Set for 2019

Directors of the California stem cell agency this morning approved a $144 million research budget for next year, which could well be its last for dispensing any major cash in its search for stem cell therapies.

The amount compares to $148 million expected to be awarded this year.  At its peak, the agency was handing out close to $300 million a year in research awards, but the amount varied from year to year.

Most of the funds for the next year will be devoted to clinical stage work. The agency, formally known as the California Institute for Regenerative Medicine (CIRM), is already backing 49 clinical trials, the last stage before a therapy is approved for widespread use. But it has yet to help finance a therapy that can be used by the population at large, despite expectations of voters who approved creation of the $3 billion agency in 2004.

CIRM expects to run out of cash for new awards next year. Possibilities exist for continued funding of research in 2020, but the agency is budgeting conservatively. CIRM Chairman Jonathan Thomas is attempting to raise privately $220 million to maintain the agency's funding. Thomas briefed directors today on that effort but notably did not report that specific additional funding had been secured.

CIRM also expects to recover possibly as much as $30 million in 2019 from projects that do not meet their milestones and possibly use the funds for awards next year or in 2020.

The agency is pinning its hopes for ultimate survival on a yet-to-be-written $5 billion bond measure on the November 2020 ballot. Sphere: Related Content

Wednesday, October 17, 2018

Where Has The Money Gone? A 10-cent Look at $3 Billion in California Stem Cell Spending

CIRM graphic
California has spent about $2.6 billion on stem cell research over the last 14 years. It has roughly $144 million left for new awards. Here is a quick overview of where cash has gone, based on the agency's records.

Keep in mind that an examination of the state stem cell agency's spending can be like the blind men and the elephant. A lot depends on what you grab.

And tomorrow directors of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, will  be grabbing a piece of the program to determine what is going to be handed out in 2019.

Since 2004 when the agency was created with $3 billion in funding, CIRM reports that it has spent $898 million on various stages of basic research, which it generally calls "discovery," the largest single category.

It has plowed $632 million into clinically connected research dealing with afflictions ranging from cancer to blindness. The amount involves both more recent clinical research and CIRM's earlier disease team programs. Kevin McCormack, senior director for communications, said the money went for late stage research leading to a clinical trial as well as the trials themselves.

The agency's clinical trial dashboard shows that it has supported 49 clinical trials. The dashboard provides more detail on the status of each trial. (Here is a link to a June CIRM spreadsheet on the trials. Here is a link to a table on the trials released in connection with this week's directors' meeting.) 

CIRM has sunk $482 million into "infrastructure," a term that includes a $271 million building program for new facilities at institutions ranging from Stanford to UC Davis.  (See here and here for more on the infrastructure program.

The agency spent $219 million on education, which probably does not include a more than $40 million program to lure star scientists to the Golden State academic institutions. Those awards were specifically for research projects.

In terms of diseases, CIRM research covers 24 disease areas, ranging from Alzheimer's to strokes. A third of the clinical trial money has gone for cancer. Nineteen percent has targeted blood diseases and 12 percent neuro afflictions.

For a full list of institutions, see here.
Stanford, an already well-endowed institution in 2004, was the top institutional recipient with $360
million. UC Davis was the over-achiever in the top 10 recipient list with $138 million. In 2004, it had what could only be described as a tiny stem cell program.

ViaCyte, Inc., of San Diego, is the only business to make the top ten list, snagging $72 million. With the exception of ViaCyte, all of the institutions in the top ten had or have representatives on the CIRM governing board who are not permitted to vote on awards to their institutions.

As mentioned at the beginning of this item, this was the 10-cent tour of CIRM spending, which may tweak your interest. The high-priced excursion will come another day.
Sphere: Related Content

Tuesday, October 16, 2018

California Stem Cell Agency's Latest Awards: Total of $17 Million for Cancer, Blindness, HIV

The California stem cell agency is set this Thursday to award $3.8 million for research aimed at development of a major improvement in treatment for HIV and another $13.5 million to deal with leukemia and problems that can lead to blindness. 

The proposals have already been approved by the $3 billion agency's reviewers in a closed door session. The governing board of the agency is expected to ratify those decisions at a public meeting on Thursday. 

Xiuli Wang, COH photo
The HIV award is scheduled to go to Xiuli Wang of the City of Hope in the Los Angeles area for work leading to a clinical trial. Wang told the board in a letter, 
"(O)ur approach has the potential to be a single delivery therapy that releases patients from the ART (antiviral drug therapy) regime for the rest of their lives. This strategy could also alleviate the cumulative financial burden that represents life-long medication."
In response to a query from the California Stem Cell Report, Jeff Sheehy, an HIV patient advocate on the CIRM board, said that the proposal (CLIN1-11223) would use a vaccine to "to stimulate one's immune system to proliferate and maintain the engineered anti HIV CAR T cells that are the therapy.
"What makes this especially exciting is that 'the approach of using the CMV vaccine to expand CMV specific T-cells may eliminate the current use of preconditioning chemotherapy that is widely adopted for T cell therapies.'  In short, if successful, this approach would not only give people with HIV the ability to control the virus long term with needing antiretroviral therapy but could also make CAR T therapies in general more efficient and effective as well as safer, plus lead to other uses of CAR T technology."
Theodore Leng, Stanford photo
Karin Gaensler, UCSF photo
Karin Gaensler of UC San Francisco is slated to receive $4.2 million to develop a vaccine that will attack residual leukemia cells.   (Application number TRAN1-11259)

Theodore Leng of Stanford is scheduled to be awarded $4.2 million to develop a "purified allogeneic cell therapy product (called NeuBrightfor treatment of dry age-related macular degeneration."  (Application number TRAN1-11300)

The board is also expected to approve $5.1 million for an "autologous regenerative cell  therapy for blindness." The identity of that investigator has not yet been released by the stem cell agency. (Application number TRAN1-11265)

Sphere: Related Content

Friday, October 12, 2018


Based on inaccurate figures on the stem cell agency web site, the NIH/CIRM sickle cell item on Oct. 9,2018, incorrectly reported that the agency had committed more than $200 million to sickle cell research. The correct amount is $38.8 million. CIRM said that the error was created by a computer glitch and that it has corrected the figures on its site. The item has also been corrected.  Sphere: Related Content

Go-ahead Given on $144 Million California Stem Cell Research Budget for Next Year

The California stem cell agency is moving ahead with a proposed $144 million research budget for the coming year, slightly below the $148 million expected to be handed out this year.

However, the award budget for 2019 is well below the $300 million in awards that were made in some past years.

The 2019 plan yesterday cleared the Science Committee of governing board of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known. It is expected to be approved by the full board at a meeting next Thursday.

The committee also juggled some financing and all but assured that six highly rated applications that were stalled will now receive approval, also probably next Thursday.

You can read more about the 2019 research budget here and the stalled awards here.  Sphere: Related Content

Thursday, October 11, 2018

Stalled California Stem Cell Projects Now Set for Financing: Bladder Cancer, Autism, Deafness, Blindess Among the Targets

Key directors of the California stem cell agency this afternoon moved to juggle some cash and fund six research proposals ranging from bladder cancer to autism, which had been stalled since July.

The action by the directors' Science Subcommittee came only hours after the affected researchers and patients appealed to another board group to approve the funding. It was stalled because of budgetary issues.

Those financial issues came up again before the Science Committee which approved a workaround on the $7.9 million needed to approve the research. The action may receive final approval by the full board next Thursday.

You can read more here about the session earlier in the day.   Sphere: Related Content

Stem Cell Scientists' Hopes for Research Cash Survive Another Round in California

(Late News Break: It looks like the six applications in the story below are now headed for approval, perhaps as early as next Thursday. See this story.)

Six stem cell research proposals targeting bladder cancer, autism, liver failure and more escaped rejection today as the $3 billion California stem cell agency struggles with its finances.

The agency expects to run out of cash for new awards by the end of next year. In 2019, it is considering awarding only $144 million compared to $300 million in some years. "We are coming to the end," said CIRM board member Oswald Steward, director of the Reeve, Irvine Research Center at UC Irvine, in July.

The applications had already been held over from July when the agency's directors were presented with a $19 million list of applications approved by its out-of-state reviewers in an earlier closed-door session.

However, the round was budgeted for only $10 million by the governing board of the agency, known formally as the California Institute for Regenerative Medicine (CIRM).

Ten letters of support were filed on behalf of five rejected awards, whose scores ranged from 90 to 87. The agency in July approved three awards with scores of 85.

Some of the researchers and supporters appeared before the board today. Philip Beachy of Stanford, who is seeking $1.4 million for bladder cancer research, said his team was seeking a long term cure for bladder, which has a tendency to recur and is the most expensive cancer to treat per patient.

Other researchers and patients also made a direct appeal to CIRM directors, and on an 11-0 vote, the board kept the applications alive during a telephonic meeting.

Here is a link to the scores and review summaries in this round. Here is the presentation by staff on its recommendations.

Here is a list of letters supporting applications in this round and their authors:
Sphere: Related Content

Wednesday, October 10, 2018

Dollars Dribbling Away: California Stem Cell Scientists Appeal for More Research Cash

When the cash spigot starts to dry up, the appeals stack up.

Such is the case this week at the now $144 million California stem cell agency, which has been mostly referred to as a $3 billion enterprise. But the cash is dribbling away quickly. And the agency is sticking to its budget in a way that did not happen eight years ago.

The latest evidence comes on the agenda for Thursday's meeting of directors of the agency, known formally as the California Institute for Regenerative Medicine or CIRM. The agenda contains 10 letters appealing to the directors to approve awards for various research projects.

These are projects that have been recommended for funding by the agency's scientific reviewers. However, the reviewers did not have the constraints of meeting the agency's budget for this round of awards.

Only $865,282 is available under the agency's budget. The five applications in question total close to $7 million.

So letters appealing for the cash have been directed to the agency's board.
Here are a couple of samples from the letters.

Phil Beachy, Stanford photo
This one is from Philip Beachy of Stanford University, whose application (DISC2-11105), Beachy wrote, was scored at 90 out of 100 by reviewers. He is seeking $1.4 million for work related to bladder cancer.
"In July we were surprised to learn that our application was not selected for funding, whereas four proposals ranked below ours were funded. We have subsequently learned that an important component of the funding decision made by the ICOC (the CIRM board) is comments from scientists and patient advocates. We wish to have the opportunity to present our comments at the October 11 ICOC meeting, at which our proposal will be considered. Four scientists involved in this proposal will be attending the meeting, including myself (Philip Beachy, Ph.D.), Kyle Loh, Ph.D., Lay Teng Ang, Ph.D., and Joe Liao M.D., Ph.D.)." 
They also enlisted assistance from a patient advocate, Don Reed of Fremont, who is a regular at CIRM board meetings. He wrote,
"Is there a path to defeating the cancer and restoring the bladder’s natural function? Today I had lunch with two people, Drs. Lay Teng Ang and Kyle Loh, who (along with Drs. Philip Beachy and Joe Liao) may have the answer to this particular cancer. Their goal is to use embryonic stem cells to grow a healthy new lining of the bladder....But they need a grant from the California stem cell agency to do it."
Robert Rainey, USC photo
Here is an excerpt from another letter. This one was written by Robert Rainey, the primary research associate involved in an application (DISC2-11183) that seeks $833,282 to create a screen to protect against hearing loss caused by chemotherapy.  The proposal by Neil Segil, co-director of the USC Hearing and Communications Neuroscience Training Program, received a score of 87 from reviewers.

Rainey, who is profoundly deaf, wrote,
"In the entire history of CIRM, only three hearing loss-related grants have been awarded. This is not an oversight of CIRM, but rather a reflection of the paucity of experimental approaches for studying problems related to hearing loss in humans. Our approach can now overcome these problems, and the work described in this proposal will allow us to simultaneously improve the efficiency of our direct-reprogramming technique from human iPSCs, while allowing us to immediately begin pilot testing small libraries of FDA-approved drugs for hair cell-protective qualities during cancer treatment."
(Rainey's letter is in the same file as Segil's.)
Segil wrote,
"Talk about adding insult to injury! Imagine that you are the parent of a 4 year old child who has just been diagnosed with a deadly pediatric cancer. You are told that, in spite of this horrible diagnosis, a cure is possible, with a good chance of success. However, the cure has an extremely common side-effect, namely that your child will likely go deaf as a result of the chemotherapy. In fact, more than 60% of kids treated for pediatric cancer end up profoundly deaf."
Neither Segil's or Beachy's applications will be funded if the board sticks with its budget and abides by staff recommendations, which it has usually done in recent years.

You can find on the meeting agenda all the appeal letters, summaries of the application reviews and CIRM's rationale for the last award in this roundThe transcript from the July board meeting also carries considerable discussion related to the financial pressures generated in this round along with how the initial decisions were made. Sphere: Related Content