Dendreon shocked the cancer research world back in April, proving for the first time in a major clinical trial that a drug which actively stimulates the immune system can be effective against tumors. Now the Seattle-based company has to wrestle with a whole new set of challenges to make sure it fully exploits the potential … Continue reading “Five Big Questions For Dendreon’s Analyst Day”
Author: Luke Timmerman
Luke is an award-winning journalist specializing in life sciences. He has served as national biotechnology editor for Xconomy and national biotechnology reporter for Bloomberg News. Luke got started covering life sciences at The Seattle Times, where he was the lead reporter on an investigation of doctors who leaked confidential information about clinical trials to investors. The story won the Scripps Howard National Journalism Award and several other national prizes. Luke holds a bachelor’s degree in journalism from the University of Wisconsin-Madison, and during the 2005-2006 academic year, he was a Knight Science Journalism Fellow at MIT.
The San Diego Biotech Survival Index: Local Firms Make Strong Rebound In First Half of 2009
When Xconomy published its first analysis of the financial health of San Diego’s publicly traded biotech companies last November, half of the nation’s 248 unprofitable biotechs were running on fumes, with less than a year’s worth of cash in the bank. A lot of predictable, painful cuts have followed. Yet a majority of San Diego’s … Continue reading “The San Diego Biotech Survival Index: Local Firms Make Strong Rebound In First Half of 2009”
Biotech Pioneer Steve Gillis on Life as a VC, How Today’s Entrepreneurs Can Make It, and Seattle’s Future in Life Sciences (Part 1)
Most Seattleites would probably list Bill Gates, Paul Allen, Howard Schultz, and Jeff Bezos when asked to name local entrepreneurs who built not just successful companies but entirely new industries. But they’d be forgetting Steve Gillis. Gillis would have to be considered something like the Fifth Beatle in a group like that—you can walk into … Continue reading “Biotech Pioneer Steve Gillis on Life as a VC, How Today’s Entrepreneurs Can Make It, and Seattle’s Future in Life Sciences (Part 1)”
Gov. Gregoire “Committed” to Biotech Fund While Juggling DC Health Reform, Economy
Gov. Chris Gregoire has been in the thick of the health care reform talks in the other Washington. To hear her tell the story, she has been talking with President Obama’s top health policy aide, Nancy Ann DeParle, U.S. Health Secretary Kathleen Sebelius, House Speaker Nancy Pelosi, and one of the leading Senators on health … Continue reading “Gov. Gregoire “Committed” to Biotech Fund While Juggling DC Health Reform, Economy”
The Seattle Biotech Survival Index: Companies Bounce Back in Mid-2009
Seattle’s biotechnology industry is in significantly better financial shape than it was six months ago. The turnaround has been nothing short of amazing, thanks to a frantic run of dealmaking, cost-cutting, and remarkable clinical trial results that have made local companies some of the best-performing stocks this year on the NASDAQ. Indeed, while our first … Continue reading “The Seattle Biotech Survival Index: Companies Bounce Back in Mid-2009”
Lee Hood’s New Idea, Integrative Diagnostics for Early Cancer Detection, Raises $7.5M
[Update: 09/21/09, 6:27 pm. See below.] Leroy Hood’s new idea for a company that detects cancer at its earliest, most treatable stages in the bloodstream has gotten some venture capital after a year of effort. Seattle-based Integrative Diagnostics has secured $7.5 million out of a $30 million equity round, according to a filing with the … Continue reading “Lee Hood’s New Idea, Integrative Diagnostics for Early Cancer Detection, Raises $7.5M”
Seattle Companies Most Flush With Venture Cash Are Still Cutting Jobs
When a startup company raises a big wad of venture capital, logic would say they are likely to hire a bunch more smart people. That may have been true in the past, but lately we’ve spotted a disturbing trend: Some of the Northwest companies with the biggest recent VC cash infusions have instead been cutting … Continue reading “Seattle Companies Most Flush With Venture Cash Are Still Cutting Jobs”
Novo Nordisk’s Historic Mistake is Seattle’s Future Gain, Says Novo CEO
Seattle might never have gotten its newest biotech research center if not for a historic corporate blunder from 30 years ago, according to Lars Rebien Sorensen, the CEO of Novo Nordisk. Novo, the Danish drugmaker that is the world’s biggest producer of insulin for treating diabetes, was approached then by a small biotech company from … Continue reading “Novo Nordisk’s Historic Mistake is Seattle’s Future Gain, Says Novo CEO”
How Did Calypso Raise $50M? The Story Behind Seattle’s Biggest VC Deal of 2009
Word out of Calypso Medical Technologies the past year hasn’t been what most people would call positive. The Seattle-based medical device company cut one-fifth of its staff in December. Even in its third year on the market, it was still struggling to get Medicare to pay for its devices that pinpoint radiation in ways that … Continue reading “How Did Calypso Raise $50M? The Story Behind Seattle’s Biggest VC Deal of 2009”
Ambrx Strikes Deal With Wyeth (Soon-to-be Pfizer) to Make Antibody Drugs
Ambrx has ginned up yet another potentially lucrative Big Pharma deal. The San Diego-based biotech company has struck a worldwide partnership with Madison, NJ-based Wyeth to create new engineered antibody drugs against multiple diseases. Financial terms aren’t being disclosed, but Ambrx says it is raking in an upfront payment, research funding, milestone payments based on … Continue reading “Ambrx Strikes Deal With Wyeth (Soon-to-be Pfizer) to Make Antibody Drugs”
Arena Obesity Drug Passes Second Trial, Aims to Sell Safe Option for Millions of People
Arena Pharmaceuticals can breathe a sigh of relief. Twelve years of work and $1 billion invested in drug development isn’t going down the drain. The San Diego-based company is reporting today that it has passed the second big clinical trial it needs to win FDA approval to sell an obesity drug that has potential to … Continue reading “Arena Obesity Drug Passes Second Trial, Aims to Sell Safe Option for Millions of People”
Calypso Medical Raises $50M to Strengthen Pinpointed Radiation Therapy for Cancer
Calypso Medical, the Seattle-based developer of technology that pinpoints radiation therapy for cancer to minimize side effects, has raised $50 million in the biggest venture financing of the year in the Northwest life sciences industry. The financing for Calypso was led by Skyline Ventures, and the same venture firm that founded the company—Seattle-based Frazier Healthcare … Continue reading “Calypso Medical Raises $50M to Strengthen Pinpointed Radiation Therapy for Cancer”
Tysabri’s Tally of PML Cases Reaches 13
Biogen Idec and Elan’s fast-growing multiple sclerosis drug, natalizumab (Tysabri), has been connected to 13 cases of a potentially fatal brain infection, according to an FDA notice reported on today by Bloomberg News. Cases of progressive multifocal encephalopathy, or PML for short, have been adding up since the drug was re-introduced to the U.S. market … Continue reading “Tysabri’s Tally of PML Cases Reaches 13”
VentiRx, Evangelist for Lean, Mean Virtual Way, Makes Progress With Cancer, Allergy Drugs
Virtual companies have been all the rage for some time with biotech venture capitalists, but I’ve been wondering whether this lean-and-mean outsource-darn-near-everything model is really a better way to develop drugs than the traditional soup-to-nuts approach at companies like Genentech. I haven’t seen a good academic paper on this question, and until I do, I’m … Continue reading “VentiRx, Evangelist for Lean, Mean Virtual Way, Makes Progress With Cancer, Allergy Drugs”
Omeros Moves Closer to IPO, Zymo Drug Fails Arthritis Trials, Uptake Medical Gets $3.4M, & More Seattle-Area Life Sciences News
One of Seattle’s biotech companies showed it’s willing to stick its neck out to see whether the IPO window is really going to open this fall or not. —Omeros, the Seattle biotech company developing a treatment to help people recover faster from knee surgery, has been getting its ducks in a row to go public … Continue reading “Omeros Moves Closer to IPO, Zymo Drug Fails Arthritis Trials, Uptake Medical Gets $3.4M, & More Seattle-Area Life Sciences News”
Autism Gets a Boost: Seaside Therapeutics Raises $30M To Develop First Drugs That Might Work
Seaside Therapeutics, a stealthy biotech startup in Cambridge, MA, has raised $30 million to further develop research from MIT neuroscientist Mark Bear that has the potential to create the first drugs that treat the underlying neurological disorder at work in patients with Fragile X syndrome and autism. Seaside raised the money from a private, family … Continue reading “Autism Gets a Boost: Seaside Therapeutics Raises $30M To Develop First Drugs That Might Work”
Omeros Moves Closer To IPO, Sets Price Goal
Omeros, the Seattle biotech company that’s attempting to pull off the first IPO from a Washington company in two years, took a step closer toward its goal today by updating its prospectus and stating it hopes to go public at a range of $10 to $12 a share. Xconomy broke the news last month based … Continue reading “Omeros Moves Closer To IPO, Sets Price Goal”
3Tier Cuts Staff After Raising $10M to Find Best Spots for Clean Energy
Seattle-based 3Tier Group, the company that raised $10 million in venture capital last December to help developers find ideal locations for renewable energy facilities, had a staff layoff today, according to a company spokesman. Xconomy received a tip today that 19 employees were let go. The company had 85 people on the payroll the last … Continue reading “3Tier Cuts Staff After Raising $10M to Find Best Spots for Clean Energy”
Helicos Biosciences, Running Low on Cash, Snaps Up $10M Lifeline
[Update: 09/16/09, 11:15 am] Helicos Biosciences has gotten a lifeline, at least temporarily. The Cambridge, MA-based maker of genetic analysis instruments which hired an investment banker two weeks ago to seek “strategic alternatives” as it ran low on cash, has raised $10 million from new and existing investors and CEO Ron Lowy. [The deal includes … Continue reading “Helicos Biosciences, Running Low on Cash, Snaps Up $10M Lifeline”
MicroRNA Drug Developer Santaris Establishes Toehold in San Diego With Isis Veteran
Santaris Pharma, the Danish company that has pushed the first microRNA therapy into clinical trials, is opening a U.S. subsidiary in San Diego to take advantage of the talent pool of people familiar with cutting-edge RNA-based therapies. As it turns out, that includes Art Levin, a former leader of drug development at Carlsbad, CA-based Isis … Continue reading “MicroRNA Drug Developer Santaris Establishes Toehold in San Diego With Isis Veteran”
State Hands Out $5.1M Biotech Grants
The state’s Life Sciences Discovery Fund announced today that six new research projects will receive $5.1 million combined in funding. The projects will finance research into bone healing, improving limb amputation procedures, enhancing cancer treatment, and generating a wheat variety that’s safe for people with celiac disease. The grants are going to scientists at the … Continue reading “State Hands Out $5.1M Biotech Grants”
Celladon, Developer of Gene Therapy for Heart Failure, Secures Part of $24.6M Venture Round
Investors haven’t completely turned their backs on gene therapy, at least not on Celladon. The San Diego-based company raised another $2.8 million in recent weeks to keep operating until it sees results from a clinical trial that will show whether it has a groundbreaking gene therapy for people with congestive heart failure. The latest financing … Continue reading “Celladon, Developer of Gene Therapy for Heart Failure, Secures Part of $24.6M Venture Round”
Medical Device Pioneer David Auth Seethes Over $40 Billion Industry Tax Idea, FDA Delays
One of Seattle’s medical device industry pioneers has a beautiful view of Lake Washington from his home office in Kirkland, but a few minutes after I arrived, he was steaming mad. “Our government rewards dummies and punishes geniuses,” says David Auth, the inventor of a less-invasive way to clear out blockages in arteries, called Rotablator. … Continue reading “Medical Device Pioneer David Auth Seethes Over $40 Billion Industry Tax Idea, FDA Delays”
CombiMatrix Gets $1.5M Contract
CombiMatrix, the Mukilteo, WA-based maker of genetic analysis tools, said today it has received a $1.5 million contract from the U.S. Air Force Research Laboratory. The company (NASDAQ: [[ticker:CBMX]]) is being asked to develop semiconductor automated tools that detect biological, chemical, and environmental hazards that may affect the health of soldiers. CombiMatrix has developed other … Continue reading “CombiMatrix Gets $1.5M Contract”
Amylin, Dark Horse of the Obesity Drug Battle, Follows Fast Behind Arena, Orexigen
The competition to create new obesity drugs is usually portrayed as a three-way battle royal among San Diego’s Arena Pharmaceuticals, crosstown rival Orexigen Therapeutics, and Mountain View, CA-based Vivus. Yet there’s one more San Diego biotech company with a drug in an earlier phase of development, Amylin Pharmaceuticals, which may just have the most effective … Continue reading “Amylin, Dark Horse of the Obesity Drug Battle, Follows Fast Behind Arena, Orexigen”
Why Aren’t There Good Drugs for Autism? Ex-MDRNA Exec Takes a Shot at Pharma’s Neglected Disease
[Corrected: 09/14/09, 12:40 pm. See below.] Autism has stumped drug developers for a long time. Scientists say they don’t really know what causes it. There’s a long list of symptoms, from social isolation, to obsessive behaviors like staring at ceiling fans, to difficulty with language. So it’s hard for drug developers to form a strategy … Continue reading “Why Aren’t There Good Drugs for Autism? Ex-MDRNA Exec Takes a Shot at Pharma’s Neglected Disease”
Uptake Medical Nabs $3.4M
Uptake Medical, the Seattle-based developer of a minimally invasive device to treat chronic obstructive pulmonary disease, has raised $3.4 million out of a total equity offering worth $13.3 million, according to a regulatory filing. Uptake is developing a device that’s supposed to seal off access to diseased parts of the lung where air gets trapped, … Continue reading “Uptake Medical Nabs $3.4M”
Acceleron, Bucking Conventional Wisdom, Pushes Ahead Drug For Bone Loss, Anemia
A basic search of scientific literature says that Cambridge, MA-based Acceleron Pharma is trying to do something that won’t work. Past experiments suggest that a drug like its lead candidate is more likely to cause people to get anemia, not help treat it. But Acceleron has witnessed the unexpected in small human studies, and it’s … Continue reading “Acceleron, Bucking Conventional Wisdom, Pushes Ahead Drug For Bone Loss, Anemia”
Quidel, Pulling Off a Turnaround, Predicts Record Profit on Demand for Flu Tests
Quidel’s woes from earlier this year look like ancient history now, thanks to surging worldwide demand for its quick diagnostic flu tests. The San Diego-based company said today that it expects to eclipse its quarterly sales and profit records as health officials stock up in anticipation of a worsening global flu pandemic. Quidel (NASDAQ: [[ticker:QDEL]]) … Continue reading “Quidel, Pulling Off a Turnaround, Predicts Record Profit on Demand for Flu Tests”
Zymo Drug Fails Arthritis Trials
ZymoGenetics (NASDAQ: [[ticker:ZGEN]]), the Seattle-based biotech company, said today in a regulatory filing that the atacicept drug it developed and licensed to Merck KGaA has failed to reach its goal of controlling rheumatoid arthritis in a pair of mid-stage clinical trials. The study confirmed the biological effect of atacicept, and researchers saw no unexpected side … Continue reading “Zymo Drug Fails Arthritis Trials”
What Will Seattle Biotech Be Like in 20 Years? Xconomy Event Looks Far Into Region’s Future
[Updated, 3:15 pm Sept. 11 with added “burst” from Immune Design.] Seattle biotech has taken its share of lumps lately, but beyond the next quarter or next year, what kind of life sciences potential really exists here in the Northwest? Over the next 20 years, will this area have grown as a world leader in … Continue reading “What Will Seattle Biotech Be Like in 20 Years? Xconomy Event Looks Far Into Region’s Future”
Ambit Biosciences, In Third Incarnation, Gears Up for Pivotal Study of Leukemia Drug
Biotech companies run into walls all the time, and either reinvent themselves or die. If they’re fortunate, they get one shot at a turnaround. San Diego-based Ambit Biosciences is getting a third chance, and this time it has some hard data, not just a flashy concept, to offer. Ambit got started in May 2000, just … Continue reading “Ambit Biosciences, In Third Incarnation, Gears Up for Pivotal Study of Leukemia Drug”
Targeted Genetics Lives On, CellCyte Charged With Fraud, Theraclone Finds HIV Weakness, & More Seattle-Area Life Sciences News
There were some striking highs and lows in Seattle biotech this week. —Seattle-based Targeted Genetics (NASDAQ: [[ticker:TGEN]]), the stalwart of gene therapy, needed a lifeline if it was going to survive any longer, and it got one at the last minute this week from Cambridge, MA-based biotech giant Genzyme (NASDAQ: [[ticker:GENZ]]). Targeted is handing over … Continue reading “Targeted Genetics Lives On, CellCyte Charged With Fraud, Theraclone Finds HIV Weakness, & More Seattle-Area Life Sciences News”
Anadys Starts Hep C Trial
San Diego-based Anadys Pharmaceuticals (NASDAQ: [[ticker:ANDS]]) said today it has started a mid-stage clinical trial of its lead drug candidate, ANA598, for patients with hepatitis C. The study will enroll 90 patients on the drug or a placebo, in combination with the standard treatments—pegylated interferon alpha and ribavirin. Initial results on the anti-viral activity of … Continue reading “Anadys Starts Hep C Trial”
Vivus, Rival to Arena and Orexigen, Nails Big Results in Clinical Trials of Obesity Drug
The obesity drug competition just got tougher for a pair of San Diego-based companies. Shares of Mountain View, CA-based Vivus (NASDAQ: [[ticker:VVUS]]) shot up this morning after it said its experimental obesity drug helped people lose a substantial amount of weight in a pair of clinical trials with more than 3,750 patients. Vivus reported the … Continue reading “Vivus, Rival to Arena and Orexigen, Nails Big Results in Clinical Trials of Obesity Drug”
Targeted Genetics Survives Brush With Death, Sells Gene Therapy IP to Genzyme for $7M
Targeted Genetics needed a lifeline and it got one at the last possible minute. The Seattle-based mainstay of gene therapy, which has been running on fumes for months, has struck an 11th-hour deal to stay alive another year by selling off its most valuable intellectual property for $7 million to Genzyme (NASDAQ: [[ticker:GENZ]]). Many of … Continue reading “Targeted Genetics Survives Brush With Death, Sells Gene Therapy IP to Genzyme for $7M”
OVP Company Does 14 Genomes
Complete Genomics, the Mountain View, CA-based company with a goal of sequencing full human genomes for $5,000, is announcing today that it has completed 14 full human genome sequences for commercial customers like March. The company says it has a dozen customers, including Pfizer, Duke University, the Institute for Systems Biology in Seattle, and the … Continue reading “OVP Company Does 14 Genomes”
SEC Charges CellCyte With Stem Cell Fraud
CellCyte Genetics, the Bothell, WA-based company that once said it was on the verge of entering clinical trials with a stem cell compound to repair the heart, has been charged with violating federal securities laws by making false statements to investors. Today in U.S. District Court in Seattle, the company, its former CEO, and former … Continue reading “SEC Charges CellCyte With Stem Cell Fraud”
Seattle Genetics Gets Milestone
Seattle Genetics (NASDAQ: [[ticker:SGEN]]) said today that it achieved a milestone under its partnership with Bayer Schering Pharma AG of Germany. The Bothell, WA-based company provided Bayer with a license to its technology for linking antibodies to toxins, with a goal of making targeted and potent anti-cancer drugs. Bayer has now submitted an application to … Continue reading “Seattle Genetics Gets Milestone”
Facet Rejects Biogen Takeover Bid
Facet Biotech (NASDAQ: [[ticker:FACT]]), the Redwood City, CA-based biotech company, said today that its board has rejected Biogen Idec’s hostile takeover offer of $14.50 a share, or about $355 million. The two companies are partners in developing daclizumab, an antibody for multiple sclerosis. Facet says Biogen is seeking to buy full rights to the drug … Continue reading “Facet Rejects Biogen Takeover Bid”
Clarisonic Skin Cleanser Cracks $40M in Sales on Kudos From Oprah and YouTube Beauty Queen
The same people who invented Sonicare toothbrushes have another emerging hit on their hands. This time, David Giuliani and his team of scientists and engineers in Bellevue, WA, who make the Clarisonic device have created a sonic-wave powered brush that’s designed to give people a cleaner, healthier-looking face. They’re marketing a $195 luxury consumer product … Continue reading “Clarisonic Skin Cleanser Cracks $40M in Sales on Kudos From Oprah and YouTube Beauty Queen”
Arena Eagerly Awaits Answer to $1 Billion Question: Does It Have a Big-Time Obesity Drug?
San Diego-based Arena Pharmaceuticals has spent a dozen years, and raised almost $1 billion from investors and partners, to create a new drug that helps millions of people lose weight. This month, the company will find out whether the time and money was well spent. Arena (NASDAQ: [[ticker:ARNA]]) plans to unveil results of a 4,008-patient … Continue reading “Arena Eagerly Awaits Answer to $1 Billion Question: Does It Have a Big-Time Obesity Drug?”
Biogen Idec Makes Hostile $350M Takeover Bid for Facet Biotech
Biogen Idec isn’t sitting around waiting to get acquired—it wants to be the acquirer. The Cambridge, MA-based biotech company said today it is making an unsolicited bid worth more than $350 million to acquire Redwood City, CA-based Facet Biotech, its partner in developing a new antibody drug for multiple sclerosis. Biogen Idec (NASDAQ: [[ticker:BIIB]]) is … Continue reading “Biogen Idec Makes Hostile $350M Takeover Bid for Facet Biotech”
Elan Breached Tysabri Partnership With Biogen Idec, Federal Judge Says
Irish drugmaker Elan breached its multiple sclerosis drug partnership with Biogen Idec when it tried to cut a separate deal to collaborate with Johnson & Johnson, according to a federal judge. Elan, which made the announcement last night, said it respects the decision of the U.S. District Court for the Southern District of New York. … Continue reading “Elan Breached Tysabri Partnership With Biogen Idec, Federal Judge Says”
Finding HIV’s Weak Spot, Scientists at Seattle’s Theraclone and San Diego’s Scripps See Opening for New Vaccine
Scientists have been trying for years to solve the mystery of why a few rare individuals get infected with HIV, yet somehow retain immune defenses so they never get sick. Today, researchers at a small Seattle biotech company, Theraclone Sciences, and collaborators at San Diego’s Scripps Research Institute say they have found a new vulnerability … Continue reading “Finding HIV’s Weak Spot, Scientists at Seattle’s Theraclone and San Diego’s Scripps See Opening for New Vaccine”
Trubion Scores $20M, Archus Shuts Down, AVI Biopharma’s Hope for Muscular Dystrophy, & More Seattle-Area Life Sciences News
One of the Seattle biotechs that’s been flying low on the radar this year popped back up on the scene with news of an important partnership. —Seattle-based Trubion Pharmaceuticals had its best day of the year last Friday, when it said it secured a partnership with Redwood City, CA-based Facet Biotech (NASDAQ: [[ticker:FACT]]) to co-develop … Continue reading “Trubion Scores $20M, Archus Shuts Down, AVI Biopharma’s Hope for Muscular Dystrophy, & More Seattle-Area Life Sciences News”
Archus Orthopedics, Spine Device Maker that Raised $60M, Shuts Down Amid Cash Crunch
Archus Orthopedics, the Redmond, WA-based developer of implants to help people retain flexibility after back surgery, is shutting down its operations and dissolving after it was unable to raise enough capital to bring the product all the way to the U.S. market, Xconomy has learned. Archus filed paperwork with the Delaware Secretary of State to … Continue reading “Archus Orthopedics, Spine Device Maker that Raised $60M, Shuts Down Amid Cash Crunch”
Gloucester Wins Recommendation from FDA Panel for Lymphoma Drug
Gloucester Pharmaceuticals likely made its venture capitalists some fast money today. The Cambridge, MA-based biotech company—which scored $29 million in venture capital last week—won an unambiguous vote of confidence today from an FDA advisory panel for its drug for a rare form of lymphoma. Gloucester’s drug for cutaneous T-cell lymphoma, romidepsin, was recommended by the … Continue reading “Gloucester Wins Recommendation from FDA Panel for Lymphoma Drug”
Gloucester Gears Up for FDA Panel Vote on Lymphoma Drug
[See update at 3:35 pm Eastern with FDA panel vote in favor.] You can bet that the people who just put $29 million into Gloucester Pharmaceuticals a few days ago will be watching very closely today for signs they got their money’s worth. The Cambridge, MA-based biotech company will try to make its case today … Continue reading “Gloucester Gears Up for FDA Panel Vote on Lymphoma Drug”
The Rosetta Diaspora: Genetics Talent Stays Close to Home After Merck Shuts Down in Seattle
Merck was the only Big Pharma company with a toehold in Seattle a year ago, so when it decided to shut down its Rosetta Inpharmatics research center last October as part of global cost-cutting, some local biotechies moaned about how this was another sign of the apocalypse for a once-thriving life sciences scene. But after … Continue reading “The Rosetta Diaspora: Genetics Talent Stays Close to Home After Merck Shuts Down in Seattle”