California Stem Cell Researchers Compete Next Week for $52 Million in Awards

Directors of the California stem cell agency will make yes-or-no decisions next week  on eight applications for $52 million to seek cures for afflictions ranging from Parkinson's to an incurable eye disease called retinitis pigmentosa.

All eight have been approved behind closed doors by the agency's grant reviewers, but it is yet to be determined whether the agency has enough cash to ratify that action.

Prior to voting on the applications, the 29-member board is scheduled to discuss how the agency's final funding will be parceled out. The agency expects to run out of cash for new awards at the end of the Oct. 31 meeting. However, also on its agenda are a few words promising a report on the status of its search for private donations. 

Below is a table on the applications. It includes links to the review summaries prepared by the agency, which is formally known as the California Institute for Regenerative Medicine. Links to the review summary can be found on the application numbers.

Some of the applicants have filed additional letters with the board seeking to bolster their pitches. The letters can be found by clicking on the researcher's name. Some of the applicants are expected to address the board personally Oct. 31 in Oakland.

The agency has a non-embarrassment policy of not disclosing the names of applicants and their institutions until a vote by its board.  However, when they write the board, their names become a public record. The names of applicants who fail to win approval are never disclosed by the agency.

Look for more stories in the upcoming days from the California Stem Cell Report on the agency's Halloween meeting.

Application Number	Amount In millions	Institution	Principal  Investigator	Target
CLIN1-11591	$5.5	Stanford	Rosa Bacchetta	IPEX
CLIN1-11472	$6.6	Not disclosed	Not disclosed	Retinitis pigmentosa
CLIN2-11620	$10.5	Not disclosed	Not disclosed	Retinitis pigmentosa
CLIN2-11661	$8.0	Brain Neurotherapy Bio	Krystof S. Bankiewicz	Parkinson’s Disease
CLIN2-11650	$10.3	UCLA	Sophia Deng	Limbal stem cell deficiency
TRAN1-11536	$4.9	UCLA	Caroline Y. Kuo	Immune deficiency
TRAN1-11555	$3.2	UCLA	Yvonne Y. Chen	Myeloma
TRAN1-11544	$2.9	Not disclosed	Not disclosed	Ovarian cancer

California's $76 Million Bet: Something Called CAR-T, Cancer and Promises

CIRM-funded researcher Saul Priceman of the City of Hope discusses the CART-T frontier, April 2019. Video by American Association for Cancer Research

California's state stem cell agency has now invested $76 million in treatments sometimes described as "miraculous," whose costs can run upwards of $1.5 million. 

The push into the much-heralded CART-T therapy field is part of the agency's effort to fulfill its 15-year-old campaign promise to state voters to turn stem cells into cures. 

The California Stem Cell Report this week took a look at the  CAR-T slice of the agency's $3 billion research pie in the wake of news that Medicare would now cover major portions of the cost of the cancer-fighting technology.

The decision applied to only two specific therapies. But Seema Verma, the top Medicare executive, said CAR-T was
"an important scientific advancement" and would provide help for "some patients who had nowhere else to turn."

Maria Millan, president of the stem cell agency, called the announcement a big step forward. In an email to the California Stem Cell Report, she said,

“We are encouraged by the announcement that the Centers for Medicare and Medicaid will provide coverage for hospital costs related to CAR-T therapies. This is a major step to providing access to these life-saving treatments for patients in need.”

The CAR-T therapies approved by Medicare can run close to $500,000 plus hundreds of thousands more for related costs. One estimate is that total cost of a CAR-T treatment could hit $1.5 million. 

Their medical promise of CART-T is that it's a cure -- not an ongoing treatment, which also can raise total costs exponentially. The idea behind the therapy is that it powers up a patient's immune system to destroy cancer cells in a targeted fashion.  

"Drugmakers note CAR T-cell therapy is designed to be given just once and to be a potential cure for patients who have run out of other options. But not all patients benefit from it and because it is so new, it’s too soon to know whether it will deliver long-term cures," Laurie McGinley wrote in the Washington Post last week. 

California's stem cell agency, formally known as the California Institute for Regenerative Medicine(CIRM), has approved 11 awards involving CAR-T therapies ranging from basic research to clinical trials. The amounts of the awards run from less than $2 million to nearly $20 million, which went to Poseida Therapeutics, Inc., of San Diego, Ca.

The company has received a total of nearly $24 million from CIRM for its CAR-T work. In May, the Food and Drug Administration approved Poseida's CIRM-backed product as an orphan drug treatment for multiple myleoma, a disease that affects 300,000 Americans every year. The company reports that its Phase Two clinical trial for the treatment is now underway.

Poseida's work has attracted the interest of Big Pharma. In March, Novartis pumped $75 million into the company in a fund-raising round that totalled more than $142 million.  (See here for more information on Poseida.)

Last month, in another CART-T venture, the stem cell agency added more millions to an effort at the City of Hope by Saul Priceman, a breast cancer researcher. He told the CIRM board,

"For the past 20 years, City of Hope has focused intensely on developing CAR-T cell approaches for treating the most intractable solid tumors. In the early 2000s, we were the first to demonstrate solid tumor CART-T cell therapy treatment in patients. And recently we were the first to report our remarkable response for patients with glioblastoma."

CIRM directors added more than $9 million to the $1.4 million already provided to Priceman.

In announcing the award, CIRM CEO Millan said, 

“When a patient is told that their cancer has metastasized to other areas of the body, it can be devastating news. There are few options for patients with breast cancer brain metastases (the target of Priceman's research).

"Standard of care treatments, which include brain irradiation and chemotherapy, have associated neurotoxicity and do little to improve survival, which is typically no more than a few months.  CAR-T cell therapy is an exciting and promising approach that now offers us a more targeted approach to address this condition.”

CAR-T is a gene therapy, which has raised some questions about whether it fits within the scope of the stem cell agency, which was created by a ballot measure in 2004, Proposition 71.  

Kevin McCormack, senior director of CIRM communications, said in response to a query, 

"The programs we’ve funded fit into Proposition 71 because (1) HSC (hematopoietic stem cell) derived CAR-T, (2) CAR T’s enriched for TSCM (stem cell) or gene-engineered T cells qualify as a 'vital research opportunity' as outlined in the proposition." 

Here are links to the CAR-T awards by their CIRM application number, which is very useful in searching for additional information on each grantee's research.

Tran1-10258, $5.6 million, Ezra Cohen, UC San Diego; Clin2-10395, $19.8 million, Matthew Spear, Poseida; Clin1-10999, Devon Shedlock, Poseida; Clin2-10248, $12.8 million, Christine Brown, City of Hope; Clin2-10846, $11 million, Crystal Mackall, Stanford; Clin1-11223, $3.8 million, Xiuli Wang, City of Hope; Disc2-11107, $1.4 million, Saul Priceman, City of Hope; Clin2-11574, $9.3 million, Priceman, City of Hope; Disc2-10748, $1.7 million, Scott Kitchen, UCLA; Disc2-11157, $1.4 million, Lili Yang, UCLA, and Clin2-11380, $4.7 million, Theodore Nowicki, UCLA.

City of Hope video

California Pumping $19 Million More into Stem Cell Effort to Improve Kidney Transplant Success

The California stem cell agency is set to make a nearly $19 million bet next week on a treatment that is aimed at significantly improving the success of  kidney transplants and helping to reduce healthcare costs.

The agency's board is expected to ratify a decision to award $18.8 million to Medeor Therapeutics, Inc.,  of San Mateo, Ca., for a phase 3 clinical trial, the last stage before its proposed product can be widely used.

Next week's award will bring to $25.4 million that the state has invested in the work. The agency awarded $6.7 million for the research in 2016.

The company's chief medical officer, D. Scott Batty, Jr.,  said last spring that its product, dubbed MDR-101, "has the potential to address the two most critical transplant patient needs: preventing organ rejection and mitigating anti-rejection treatment-associated toxicities. " He added that the technology could potentially be used in all solid organ transplant patients.

Fierce Biotech reporter Phil Taylor wrote last April,

"Patients who undergo organ transplants may no longer have to rely on lifelong immune-suppressing drugs, if Medeor Therapeutics has its way."

Taylor continued,

"More than 30,000 Americans get an organ transplant every year, and while success rates for these procedures are improving, it is estimated that up to a third of the most common transplants—such as heart, kidney, and liver—fail within 5 years."

The Medeor treatment uses adult stem cells to create a condition in which the transplanted kidney "is no longer viewed as foreign by the recipient," according a summary of the closed-door review of the company's application (CLIN2-10411). 

The agency's reviewers, who do not have to publicly disclose if they have  potential conflicts of interest, voted 11-1 to fund the research. The agency's board almost never overturns the decisions of its reviewers, who come from out-of-state. The names of persons reviewing specific applications are not disclosed by the agency, which also does not disclose the name of applicants until after board action. The California Stem Cell Report identified the firm from public records.

Samuel Strober, Stanford photo

Last November, Medeor announced it had raised $57 million in Series B financing, "led by RA Capital Management. Additional new investors included Sofinnova Ventures and 6 Dimensions Capital, who were joined by existing investors Vivo Capital and WuXi Healthcare Ventures."

The scientific founder of the firm is Samuel Strober, a professor of medicine at Stanford and who is a member of its scientific advisory board. 

The estimated date of completion of the trial is January 2022, according to clinicaltrials.gov. The governing board of the $3 billion stem cell agency is scheduled to meet Jan. 18 to approve the award. No other action is scheduled.