Friday, July 31, 2015

'Best of Times, Worst of Times' -- A Tale for Stem Cell Fans

Highlights:
Sinking stock prices vs. $40 billion market
Profits drive therapies
Test for the California stem cell agency

During the past week, followers of the stem cell world have been treated to sharply contrasting perspectives on the likely success of therapies involving regenerative medicine.

One perspective was bleak; the other robustly optimistic.

One borrowed slightly from the “Tale of Two Cities,” with a headline that said “Tale of seven stem cell stock woes….”

The other carried a headline that said “global stem cell market predicted to reach $40 billion in five years….”

One was a story about hard-eyed investors backing away from stem cell research. The other was about a bright, near-term future for the field.

Don Gibbons, chief communications officer at California’s stem cell agency, wrote about thatbright global market on his agency’sblog. He said that the $40 billion figure was generated by the worldwide consulting firm Frost and Sullivan, which was promoting its study of the field. The 2014 report is going for as much as $7,500, a price tag that helps illustrate one of the features of the stem cell field: It needs a lot of cash.

Indeed, Gibbons noted that Frost and Sullivan cautioned that funding for early stage, clinical stem cell work is not abundant.

Which brings us to Paul Knoepfler’s tale of stem cell stock “woe.” He is a stem cell researcher and blogger at UC Davis, which has benefited mightily from cash from the $3 billion California stem cell agency.

He wrote,
“Lately, stem cell companies have not been doing so well financially to put it mildly and their stock prices have generally been going down, down, and down further. A lower stock price and market capitalization are not just a headache for investors and bad for the companies, but they also strongly interfere with the progress of the clinical science.”
And he asked,
“To be blunt, why are their stocks doing so miserably?”
Knoepfler did not really attempt to answer that question. However, it is clear that stem cell stock prices are down because nobody wants to buy them. The reason? Investors do not expect to make money any time soon by purchasing shares in those firms, which struggle perennially to raise cash.

That is a financial reality that the $3 billion California stem cell agency needs to fully integrate into its plans for spending its last $800 million, which is slated to run out in less than five years.

The agency’s goal is to produce a stem cell therapy as promised to California voters 11 years ago when they approved creation of the agency, which will cost the state about $6 billion, including interest, before the effort expires.

Without backing of industry, there will be no therapies. But the priorities of a business are not necessarily the same as the agency’s. Profits necessarily come first with a business. Otherwise it will vanish into a financial abyss. Witness the dumping of the nation’s first hESC clinical trial by Geron, in which the agency invested $24 million only three months before the trial was summarily terminated by the company for financial reasons. 

The California stem cell agency’s president, Randy Mills, should understand the vagaries of all this better than most. He made his career as a biotech business executive, not as a researcher. Over the last year, he has done much to sharpen the focus of the agency and begin to create a clear path for emergence of a therapy, a “radical” change he has dubbed CIRM 2.0.

Whether he can successfully put together the needs of business and the needs of science and medicine is perhaps the key question for the California stem cell agency between now and 2020. 
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Monday, July 27, 2015

California's Salk Institute Looking for New CEO

San Diego is a hotbed of biomedical research, so when one of the leaders of its top institutions leaves, it is significant news.

William Brody, Salk photo
William Brody, head of the Salk Institute and a former director of the California stem cell agency, will be retiring at the end of the year, the San Diego Union-Tribune reported yesterday.

Brody, 71, came to Salk in 2009 and has wrapped up a $300 million fundraising effort that has stabilized the nonprofit after a period of financial uncertainty, Gary Robbins reported in the newspaper’s story.

Robbins wrote,
"'Salk has always had a much smaller endowment than other comparable institutions, but with decline in funding for biomedical research we needed a buffer and that is what Bill achieved,' said Terry Sejnowski, a Salk neuroscientist. 'None of his predecessors were able to do this. We don't have wealthy alumni or grateful patients, just the best basic science.'
"But if you compare where we are today with Scripps (Research) and medical schools around the country that are bleeding faculty and debt we are solvent if not plush, and continue to recruit the best young faculty. Looking to the future we need to find another Bill Brody."
Brody served on the governing board of the $3 billion state stem cell agency from August 2009 to the end of 2012. His predecessor at Salk, Richard Murphy, also served on the board and as interim president of the agency. Salk has not had a representative on the board since Brody left. 

Salk had received $52 million from the agency, which ranks the institute 12th on the list of recipients of awards. When Brody left the agency board in late 2011, Salk had chalked up $37 million in stem cell agency awards.

Salk officials said they will launch a nationwide search for a replacement. Scripps Research, also located nearby in the San Diego suburb of La Jolla, is also looking for a new CEO with top notch fundraising abilities. 
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Thursday, July 23, 2015

California Stem Cell Agency Ends Today's Session

OAKLAND, Ca. -- Today's meeting of the governing board of the California stem cell agency has concluded. We will have more on its proceedings during the next few days. Here is a link to the agency's press release on the meeting. It identifies the other recipient of an award ($8.5 million) made today as Mehrdad Abedi of UC Davis. Donald Kohn of UCLA received the other award ($7.4 million). 

Concerning the changes in the basic research and translation award programs, the press release said,,
"By scheduling both the Discovery and Translational awards more regularly CIRM is creating a system that helps move the most promising projects along a pipeline and also provides predictability to the grant system, making it easier for researchers to know when they can apply for funding.
"The stem cell agency estimates that each year there will be up to 50 Discovery awards worth a total of $53 million; 12 Translation awards worth a total of $40 million; and 12 clinical awards worth around $100 million."
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Parkinson's Patients Dismayed by Slow Work at California Stem Cell Agency

OAKLAND, Ca. -- Directors of the California stem cell agency today unanimously approved $40 million for a program to advance or "translate" basic research during a session that was marked by emotional pleas from Parkinson's Disease patients for much faster action.

The contingent from the San Diego area told directors and agency officials they were not moving fast enough to fund a research effort that they supported.

One patient advocate, Jenifer Raub of San Diego, said it was "outrageous" that the effort could not even be considered by reviewers until next March with no funding until about 2017.  Another unidentified patient said,
"Don't let policy, bureacracy and procedures stop this for another year."
Agency officials said that the time is required to meet legal requirements for the competitive grant process and reviews of the proposals that would be submitted.

Individuals appearing at the meeting were largely associated with Summit4StemCell of San Diego and have raised to $2 million to back research by Jeanne Loring, head of the stem cell program at Scripps Research in La Jolla.  The comments appeared spontaneous in reaction to the CIRM staff presentation on the new program. Loring told the California Stem Cell Report she did not organize the comments.

The agency's new, four-round, translation research program promises cash to researchers within nine months of submission. The program says that applications will be accepted in September and March of each year. Asked about the timetable, Mills told the California Stem Cell Report that it will begin in 2016.

Mills later told the board that the agency needed to be responsive to patient needs. He said he would "see if there is anything we can do." He said he would report back to the board on the matter.

(The last paragraph in this item was added about one hour after its initial posting.)


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California Stem Cell Agency Approves $53 Million for Basic Research

OAKLAND, Ca. -- Directors of the California stem cell agency this morning approved a $53 million "discovery" research program that is aimed at funding basic research and creating special incentives to help assure that it will lead to a widely used therapy.

Randy Mills, president of CIRM, said a new, $150,000 bonus award will be created as part of the program. He also said recipients will be newly required to explain how their proposal could lead to a therapy, among other things.

Mills told directors that the new requirements would help to prevent past situations in which only 5 percent of basic research awards advanced along a path towards development.

Directors voted unanimously to go forward with the effort following a discussion that focused mainly on technical details of the plan. (See here and here for additional information on the plan.) Sphere: Related Content

UCLA's Kohn Wins $7.4 Million Stem Cell Research Award

OAKLAND, Ca. -- Donald Kohn of UCLA is the recipient of a $7.4 million award from the California stem cell agency to develop a therapy to treat a rare genetic condition called chronic granulomatous disease.

Kohn's proposal was approved unanimously by the directors of the $3 billion agency meeting here this morning. The agency did not identify Kohn as the recipient. However, it was learned shortly after the approval that the Los Angeles investigator had made the application.

See here for more information on his proposal. Sphere: Related Content

$16 Million in Two Grants Approved by California Stem Cell Agency

OAKLAND, Ca. -- Directors of the California stem cell agency today approved $16 million for two clinical trials involving AIDS lymphoma and another involving a rare genetic affliction that creates immune deficiencies problems.

Names of the recipients were not immediately disclosed. See this item for more information on the awards. Sphere: Related Content

$100 Million for Clinical Stage Stem Cell Research in California

OAKLAND, Ca. -- Directors of the California stem cell agency today approved $100 million for clinical stage research for the 2015-16 fiscal year. The funds were allocated on a unanimous vote with no discussion.

The effort extends the CIRM 2.0 program, which began in January of this year. The agency awarded $25 million during the first half of this year out of a $50 million budget. Sphere: Related Content

Oakland Gains HQ of the California Stem Cell Agency

OAKLAND, Ca. -- The California stem cell agency will be moving to new headquarters this fall in Oakland, across San Francisco Bay from its current home near the San Francisco Giants ballpark.

The address of the new headquaters is 1990 Harrison Street in downtown Oakland. Details of the cost and the square footage were not immediately available. Sphere: Related Content

California Stem Cell Agency: 'Lots of Money and Lots of Time"

OAKLAND, Ca. -- The California stem cell agency today said it has committed $1.97 billion during its nearly 11 years of life and anticipates spending about $170 million to $190 million over the next five years.

Agency President Randy Mills presented the figures at a meeting of the agency's board of directors. 
He said he anticipates a "net commitment" of $170 million annually over the next five years.

He said,
 "We have lots of money and lots of time."
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California Stem Cell Meeting Begins in Oakland

Directors of the California stem cell agency today began their meeting here at 9:11 a.m. PDT with a report from Chairman Jonathan Thomas. Sphere: Related Content

Looking for Clarity at the $3 Billion California Stem Cell Agency

OAKLAND, Ca. -- Scientists and others seeking the short version of the plans for funding of basic and translational research by the $3 billion California stem cell agency should look no further than an 18-page Power Point presentation.

The explanation is available on the agency’s Web site and in some ways is better than the more prolix description offered in three formal memos. While the presentation offers a fast read, seriously interested parties will need to plow through all three documents. (See here, here and here.)

Critical to understand the direction of the agency, however, is another Power Point presentation -- this one by Randy Mills and which is not supported by a memo or other formal document. But some of what Mills lays out in the slides has been brought up at earlier meetings, the voluminous transcripts of which are available on the agency’s Web site, if you can find them.

A search of the agency’s Web site late yesterday using the term “transcript” turned up 879 results. No transcripts of remarks by Mills or of meetings of the agency’s board of directors were found in the first 14 pages of the results.

In his slides today, Mills is covering his thinking on both basic and translational funding and how therapy development should have a continuous and predictable pathway. He likes to talk about it in terms of rail lines, a homely but apt analogy.   

While we are on the subject of Power Point presentations, the agency’s slides have improved greatly since Mills became president of the agency in May 2014.  Nonetheless, Power Point presentations do not necessarily enhance understanding, especially when the presenters do little more than read the notes on the slides. The result is known as Death by PowerPoint!

Slides are no replacement for a single, nuanced, written explanation of a proposal, including charts, something more than the agency usually offers in its memos to the board. That said, their memos have also improved and are more comprehensive and straight forward than under the regime of the agency’s former president, Alan Trounson.
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Coming Up: Full Coverage of California Stem Cell Meeting Today

The California Stem Cell Report will be on the scene today in Oakland as the Golden State's $3 billion stem cell agency is set to allocate $243 million for a wide variety of research efforts plus a high school training program. News reports will be filed as warranted throughout the day.

The public can participate in the meeting at its physical site in Oakland and at teleconference locations in Beverly Hills, San Diego, South San Francisco, Stanford, Sunnyvale and two in La Jolla. An Internet audiocast is also available. Details are available on the agenda for the meeting, which begins at 9 a.m. PDT. Sphere: Related Content

Wednesday, July 22, 2015

NDA Appoints Ellen Feigal as Partner

Ellen Feigal, formerly the No. 2 person at the $3 billion California stem cell agency, yesterday was named as a partner in NDA Partners, an international consulting firm to the medical products industry.

Feigal resigned last fall as senior vice president at the stem cell agency, about five months after Randy Mills was named as its new president.

NDA's web site says it is a "a global strategy consulting firm specializing in expert product development and regulatory advice to medical products industries" and that it deals with "emerging biopharma." The web site does not disclose the names of its clients, and it is not known whether any are involved with the California stem cell agency. Sphere: Related Content

Full Coverage of Tomorrow's Stem Cell Meeting

The California Stem Cell Report will provide gavel-to-gavel coverage tomorrow of the directors' meeting of the $3 billion California stem cell agency. Up for consideration are plans for spending $243 million, among other things.

The public can participate in the meeting at its physical location in Oakland and at teleconference locations in San Diego, South San Francisco, Stanford, Sunnyvale and two in La Jolla. An Internet audiocast is also available. Details are available on the agenda for the meeting, which begins at 9 a.m. PDT. Sphere: Related Content

Tuesday, July 21, 2015

California Ready to Approve $243 Million for New Stem Cell Research

CIRM President Randy Mills uses a railroad analogy for therapy development

The California stem cell agency Thursday is set to approve $243 million to finance everything from testing therapies on patients to exposing high school students to research.

The multi-faceted effort will come before the 29 directors of the agency at their meeting on Thursday at the Oakland Marriot City Center. The initiatives have already cleared the directors’ Scientific Subcommittee.

The effort is the second installment in the CIRM 2.0 program begun earlier this year by the agency’s president Randy Mills. He assumed his post in May 2014 at the California Institute of Regenerative Medicine or CIRM, as the $3 billion agency is formally known.

Mills has described his changes as radical. He says they are aimed at improving the quality of applications and speeding development of therapies. He also has called for deeper involvement by the agency in the direction and work of researchers.

Mills, who has made his entire career in the biotech business, says he wants to provide a relatively smooth track, a “continuous, predictable pathway” from basic research to clinical applications. He uses a railroad analogy to illustrate the desired progression of research(see graphic above).

The $243 million up for approval this week is about 30 percent of the agency's remaining $800 million. However, the money will be spent over the next several years -- not just this year. Under Mills' spending projections, the agency will not run out of cash until 2020. 

The largest program coming before CIRM directors this week is $100 million during 2015-16 for more advanced research related to clinical development. Directors earlier approved $50 million for the effort for the first six months of this year. However, they have awarded only $25 million as of the end of June.

Another $53 million is set for a variety of mostly basic research, which Mills calls “discovery.” Requests for applications are scheduled to begin late this summer or fall. Some of the rounds will have application openings twice a year.  Cash is scheduled to flow to researchers within about 10 months of application.

Mills is also asking the board for substantial delegation of authority to him during the reviews and is calling for an “optimized review process” because of a high anticipated volume of applications in discovery.

Under the $40 million translation research round, Mills would also be delegated authority in the grant review process to pluck out applications and advance them even if reviewers disagreed. Applications will be accepted in September and March. Cash will flow to researchers about nine months after applications are submitted.

Both the discovery and translation rounds are open to both businesses and nonprofit enterprises.

A revised training program called “Bridges 2.0” for college level students is budgeted for $46 million over a five-year period. A training program for high school students, changed and rebranded as “Spark,” will receive $4 million over five years. Applications for that program are due Oct. 1. It is open to colleges, universities and non-profit academic institutions. 

Applications for the Bridges program are also due Oct. 1. They will be limited to “California public universities or colleges or private, nonprofit academic institutions, which did not receive a CIRM-funded Major Facility or Shared Research Laboratory Award (and, hence, do not have a major stem cell research program or a critical mass of stem cell researchers).”

In addition to the Oakland location of the directors' meeting, the public can participate at teleconference locations in San Diego, South San Francisco, Stanford and two in La Jolla. Addresses can be found on the agenda, which includes directions for listening to the Internet audiocast of the meeting.

Email comments for the CIRM directors on items on the agenda may be sent to mbonneville@cirm.ca.gov.

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Monday, July 20, 2015

California to Hand Out $16 Million for Stem Cell Research This Week

The California stem cell agency this Thursday is scheduled to give away nearly $16 million for clinical trials for possible therapies connected to AIDs and a rare genetic affliction involving immune deficiencies.

The larger of the two awards -- $8.5 million -- will go to an unidentified recipient for an early stage trial involving AIDS-lymphoma patients.

The agency’s blue-ribbon reviewers earlier voted 10-0 behind closed doors to approve the application. On Thursday, the full board of the agency will ratify the vote in public. The board has almost never overturned a decision by reviewers to fund an award.

The summary of the review of the application, which was not disclosed, said that the proposed therapy “would be a significant improvement over standard of care in the proposed AIDS lymphoma patient population. 
“With the proposed patient population (AIDS lymphoma patients), impact will be somewhat limited. However, demonstration of success in this limited context would serve as an impetus to solve additional problems such as non-ablative conditioning to achieve engraftment in the larger HIV patient population.” 
Despite another “paucity of patients,” the stem cell agency is also expected to approve $7.4 million for an early stage trial involving X-linked chronic granulomatous disease.

Reviewers voted 5-1-4 to approve the application. The voting translates to five for the application, one indicating it needs improvement and four indicating that it is “sufficiently flawed that it does not warrant funding, and the same project should not be resubmitted for review.” 

“Reviewers were…divided as to the feasibility. Some reviewers did not think that there are sufficient patients afflicted with this disease who also meet the enrollment criteria to allow for completion of the trial with enough patients to yield meaningful outcomes. Other reviewers were optimistic that, given the track record of this team and the willingness of patients with intractable orphan diseases to participate clinical trials, the trial could be fully enrolled and yield results to potentially support moving the therapeutic toward approval by the FDA and/or advance the field.” 
The target of the potential therapy is an inherited condition that weakens the immune system. According to the Rare Disease Network, it occurs in only one out of every 250,000 persons. Only 20 new cases a year are reported in the United States, according to Wikipedia. The review summary used the expression “paucity of patients.”

Reviewers said, however, the approach has “potential value in a number of other diseases.”

The application carried with it $4.6 million in co-funding promised in a publicly unspecified form via the applicant.

Both the applications had been reworked and resubmitted to the agency under its new CIRM 2.0 award process. However, this week is the first time the board has considered them.

(Please note that the agency has cobbled together the review summaries for both applications. That means that some readers seeking the summary related to the $8.5 million award could be misled when the immune deficiency award turns up at the top of the document. The full application is also never disclosed by the agency, only the summary.) 

Rejected by reviewers was a $2.9 million application from another unidentified group. The vote was 2-6-3, meaning that the proposal can be reworked and resubmitted.

The board’s meeting will be in Oakland at the Marriott City Center. Public teleconference locations will be in San Diego, Stanford, South San Francisco and two in La Jolla. The public, including scientists, can participate from those locations as well as in Oakland.

An audiocast is also available. Full details can be found on the agenda.

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Thursday, July 16, 2015

National Controversy Snares California Stem Cell Firm; Congressional Investigation, Presidential Politics Involved

A California stem cell firm is enmeshed today in a national flap linked to abortion, buying and selling body parts and the 2016 presidential race.

The firm is StemExpress of Placerville, just east of Sacramento in the Sierra Nevada foothills. It was mentioned in a YouTube video that was recorded secretly by abortion foes who were posing undercover in a discussion with Planned Parenthood officials.

The video has been viewed nearly two million times as of this writing. The New York Times, the Washington Post and other major news outlets are covering the story.  It has triggered virulent headlines on anti-abortion and conservative web sites.

One headline on inquisitor.com said in red type,
“Buying And Selling Aborted Fetus Body Parts For $30 To $100? ‘Stem Express’ Website Down After Undercover Video Exposes Planned Parenthood” 
StemExpress provides researchers with “high-quality stem cells they need for their research,” an employee of the firm told the California Stem Cell Report in an email last May.  The firm also supplies “human blood, tissue products, primary cells and other clinical specimens to biomedical researchers around the world,”

Reporter Sammy Caiola wrote today in The Sacramento Bee,
“The eight-minute undercover clip, which has garnered over 1 million views (as of yesterday) and inspired the popular anti-abortion Twitter hashtag ‘#PPSellsBabyParts,’ is edited in a way to suggest Planned Parenthood and its affiliates profit from fetal tissue and organs procured during abortions, which is against federal law.”
Caiola said that the video contains “a supposed image of the StemExpress website (that) shows an order form, where users can designate type of order, number of specimens, tissue type and shipping options.”

Caiola continued,
“In a statement released by Planned Parenthood, spokesman Eric Ferrero said that while many women who undergo abortions choose to donate fetal tissue to scientific research, there is no financial benefit for either the patient or Planned Parenthood. Sometimes, Planned Parenthood is reimbursed for the cost of transporting the tissue to labs, he said.
“’We do this just like every other high-quality health care provider does – with full, appropriate consent from patients and under the highest ethical and legal standards,’ Ferrero said.” 
The California Stem Cell Report this morning asked StemExpress for comment and will carry it verbatim when it is received. However, all of the news stories so far say that the company has not responded to similar requests.

(The company responded -- see here for full text -- just as this item was posted and said,
"StemExpress prides itself on complying with all laws. Our compliance protocols and donor consents have been established by an FDA-compliant Independent Review Board. Written donor consent is required for any donation, including bone marrow, tissue of all types or blood."
(The company also said,
"Everything we provide is solely at the request of the nation’s and the world’s great research institutions. Producing the isolated cells researchers need from donated tissues requires the development of complicated, often unique, research techniques using millions of dollars of scientific equipment. We are hopeful the events of the last few days will not diminish our efforts to support the research community or hinder our partners from continuing their important work.")
The company was founded in 2010 by Cate Dyer.  Inc. magazine ranked the firm 363rd on Inc. magazine’s list of the fastest-growing private companies in America last year.

Ariana Eunjung Cha of the Washington Post wrote that GOP presidential hopefuls Ted Cruz, Jeb Bush, Ben Carson and Bobby Jindal all have spoken out on the controversy.

In Congress, Republican leaders have ordered an investigation. Jackie Calmes and Nicholas St. Fleuer of the New York Times said,
"House Republican leaders on Wednesday announced a congressional investigation of Planned Parenthood, a day after anti-abortion activists released a video of an unsuspecting official from the organization explaining how it provides fetal tissue to researchers.
 "Echoing the activists’ allegation, Speaker John A. Boehner and other top Republicans suggested that Planned Parenthood was selling fetal parts, which is illegal if done for profit. But Planned Parenthood said that while it charges for expenses such as processing and transporting, it makes no money from the fetal tissue donated by women who get abortions. The official shown in the video repeatedly says something similar to two activists posing as biotechnology representatives."

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Text of StemExpress Comments

The following is the full text of StemExpress’ comments about the ongoing controversy involving it and Planned Parenthood. The statement was sent by Beau Phillips, a spokesman for the firm, in response to a request this morning by the California Stem Cell Report.
Statement of StemExpress Concerning Recent Media Stories: 
StemExpress is a small life sciences company that supports leading research institutions in the United States and internationally—including medical schools, pharmaceutical companies, and federal agencies—to provide stem cells and other human tissue critical to medical research.  Cells produced by the physicians, scientists, medical technicians and nurses at StemExpress are currently used in research globally aimed at finding cures and treatments for cancer, diabetes, HIV/AIDS, cardiac disease, and other significant medical conditions.  StemExpress prides itself on complying with all laws. Our compliance protocols and donor consents have been established by an FDA-compliant Independent Review Board. Written donor consent is required for any donation, including bone marrow, tissue of all types or blood. 
We are proud of the role we play in helping the global research community as they strive to achieve medical breakthroughs to stamp out global disease and improve quality of life. Everything we provide is solely at the request of the nation’s and the world’s great research institutions.
Producing the isolated cells researchers need from donated tissues requires the development of complicated, often unique, research techniques using millions of dollars of scientific equipment. We are hopeful the events of the last few days will not diminish our efforts to support the research community or hinder our partners from continuing their important work.

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