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.

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

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.

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 NeuBright) for 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)

Summaries of the application reviews and scores can be found in this document.

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. 

California Researchers Score $16 Million Plus in State Stem Cell Awards

The California stem cell agency today handed out $16.4 million in research grants seeking therapies for afflictions ranging from gum disease and cancer to vision loss and Parkinson's Disease.

The award for Parkinson's was relatively tiny -- only $150,000 -- but represented a rare case in which the agency's governing board overturned its reviewers, who make the de facto decisions on awards.

The reversal came after one board member, David Higgins, of San Diego, who has Parkinson's, noted that the most common drug that Parkinson's patients take is 70 years old. He told the board.

David Higgins, CIRM photo

“I’m a fourth generation Parkinson’s patient and I’m taking the same medicine that my grandmother took. They work but not for everyone and not for long. People with Parkinson’s need new treatment options and we need them now. That’s why this project is worth supporting. It has the potential to identify some promising candidates that might one day lead to new treatments.”

The award went to Zenobia Therapeutics, Inc., of San Diego, whose president and co-founder, Vicki Nienaber, had filed an appeal on the reviewers' decision.  Another applicant rejected by reviewers, Toshio Miki of USC, also filed an appeal with the board. His appeal was not discussed. Miki's application sought $5.9 million for research involving metabolic disorders.

The largest award today, $5.6 million, went to Anthony Oro of Stanford, who will be testing a therapy to treat an affliction that creates wounds that will not heal. Dan Kaufman of UC San Diego received $5.5 million to produce "killer cells" to help people with a form of leukemia. Catriona Jamieson, also of UC San Diego, received $2.7 million for leukemia research.

Here is a link to summaries of reviewer remarks, including scores, on the three winners and the 11 other applications that were rejected in the translational awards category. (Scroll down on the page to see the reviews.)

In addition to the "discovery" award for Parkinson's, here are the names of the other winners in that category:

•  DISC1-10603, Ngan F Huang, iPSC-Derived Smooth Muscle Progenitors for Treatment of Abdominal Aortic Aneurysm, Palo Alto Veterans Institute for Research, $172,621
• DISC1-10475, Semil P Choksi, Generation of human airway stem cells by direct transcriptional reprogramming for disease modeling and regeneration, U.C. San Francisco, $238,408
• DISC1-10643, Dmitriy Sheyn, IVD rejuvenation using iPSC-derived notochordal cells, Cedars-Sinai, $241,992 
• DISC1-10598, Alice F. Tarantal, Enhanced Branching Morphogenesis and Pluripotent Cell Lineage Differentiation for Pediatric Regenerative Therapies, U.C. Davis, $235,80
• DISC1-10583, John R Cashman, Human Pancreatic Cancer Stem Cells: Developing a Novel Drug for Cancer Eradication, Human BioMolecular Research Institute, $303,894 
• DISC1-10555, Hiromitsu Nakauchi, Optimizing self-renewal signaling kinetics to stabilize ex vivo hematopoietic stem cell expansion, Stanford, $235,836 
• DISC1-10620, David J. Baylink, Bone Marrow Targeting of Hematopoietic Stem Cells Engineered to Overexpress 25-OH-VD3 1-α- hydroxylase for Acute Myeloid Leukemia Therapy, Loma Linda University, $178,967 
• DISC1-10513, Guillem Pratx, Novel metabolic labeling method for tracking stem cells to irradiated salivary glands using PET, Stanford, $235,613 
• DISC1-10522, Gerald P Morris, Identification of antigenic neo-epitopes from in vitro reprogrammed human tissue precursors for regenerative therapy, U.C. San Diego, $193,500
• DISC1-10588, Julia J. Unternaehrer-Hamm, Targeting cancer stem cells with nanoparticle RNAi delivery to prevent recurrence and metastasis of ovarian cancer, Loma Linda University, $172,870 
• DISC1-10721, Karl J. Wahlin, An IPSC cell based model of macular degeneration for drug discovery, U.C. San Diego, $232,200 
• DISC1-10516, Alyssa Panitch, Development of treatments to improve healing of ischemic wounds, U.C. Davis, $235,800 
• DISC1-10718, Alireza Moshaverinia, Gingival mesenchymal stem cells as a novel treatment modality for periodontal tissue regeneration, U.C. Los Angeles, $194,483

Here is a link to all the review summaries and scores in the round, including the 28 rejected applications.  Here is a link to the CIRM press release. 

California Stem Cell Agency Spending: Where the Money Is Going

Analysis of CIRM funding by Pat Olson, executive director of CIRM scientific activities July 2013

The California stem cell agency will have committed $472 million to translational research – a key to commercializing stem cell therapies – if it awards the full $70 million in new grants and loans slated to come before its governing board next week.

The nearly $500 million will amount to about 17 percent of its funding so far, according to an analysis last month by Pat Olson, the agency's executive director of scientific activities. The largest percentage of the agency's cash, however, will be going for “development” – 35 percent or $970 million. Olson defined “development” as “essentially our IND enabling, our preclinical development programs and our clinical development programs.”

Basic research is to receive 17 percent or about $469 million with buildings and facilities taking up $443 million or 16 percent. Training and career development has consumed about 15 percent or $414 million.

However, those calculations include $577 million in funds that have been allocated but not yet awarded. Another $491 million is “concept approved” but also not awarded. The agency's governing board could change those allocations or withdraw approval of concepts, although it has not yet shown signs that it might do so.

The agency will run out of money for new grants in 2017 and is examining the possibility of generating more cash through some sort of public-private partnership. To develop support for continued funding, the agency is under pressure to generate results that will resonate with the public and potential private funding sources. Those results are most likely to come from a late stage translational/clinical trial effort.

Here is a link to CIRM's translational portfolio as of September 2012.

(An earlier version of this item incorrectly said that the agency would run out of money for new grants in 2013. The correct year is 2017,.)