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Sleep Gene Switch Means Lights Out, Memory On, for Fruit Flies
24 June 2011. With the invention of a genetic snooze button for fruit flies, scientists will be able to precisely investigate the link between sleep and memory in aging flies as well as flies modeling disease. In today’s Science, researchers report that activating a temperature-sensitive channel in neurons connected to a fly sleep center caused the animals to drop off to sleep. Senior author Paul Shaw of Washington University, St. Louis, Missouri, led the study with first author Jeffrey Donlea, who has since moved to Oxford University, U.K. Putting the new tool to the test, the authors found that a solid nap allowed the flies to remember a courtship experience they normally would forget.
Waking animals up is easy, but putting them to bed is hard, noted John Cirrito, who is also at Washington University but did not participate in the study. Normally, scientists study sleep with sleep-deprived animals; such research has made it clear that lack of sleep interferes with memory. By taking a complementary approach, Cirrito said, the current work shows for the first time that sleep can consolidate memory.
As people and flies age, they sleep less; insomnia is also associated with Alzheimer’s and Parkinson’s diseases. With those sleepless nights comes loss of memory (though insomnia is not thought to cause Alzheimer’s). Unfortunately, Shaw says, regular use of sleeping pills can have side effects. For example, people can become dependent on the medication. Shaw hopes that the new fly model will help prove that sleep can be a good memory tonic as well as reveal chemical pathways that drug makers could tap to induce more natural sleep.
Shaw planned to study aging, not sleep per se. But in the process of activating different nerve groups, he and Donlea discovered that a dorsal, fan-shaped body in the fly brain acted as a sleep center. Although they have not defined the precise circuitry, the researchers found that when they inserted a bacterial sodium channel transgene into the neurons leading to the fan-shaped body, the flies spent more time snoozing. Aside from the extra shuteye they got, the transgenic flies slept normally. They napped in normal one-hour increments; a tap, light, or caffeine woke them; and they were active when awake. In fact, they were more active than other flies: “They have to rush to get things done before they go back to sleep,” Shaw suggested.
The researchers then set out to make flies sleep on demand. Donlea tried using optogenetics to selectively activate neurons leading to the fan-shaped body, but the blue light that activates the neurons also woke up the flies. Instead, the researchers selectively expressed a temperature-sensitive transient receptor potential cation channel in neurons projecting to the fan-shaped body. Upon warming, the channel opens, activating the neurons to fire (Hamada et al., 2008). A toasty 31 degrees Celsius was like a sleeping pill for these flies. “And we can make them take it,” Shaw said (see video).
http://www.alzforum.org/new/detail.asp?id=2816
Because the fan-shaped body and the neighboring ellipsoid body are associated with memory (Liu et al., 2006; Wang et al., 2008), the researchers studied how well their remote-control sleepers remembered. To do that, they used courtship training. Donlea put sexually naïve male flies together with male flies that, unfortunately for both parties, produced female pheromones. The naïve male chased its unreceptive partner around for three hours in vain.
Normally, naïve flies do not recall this incident; two days later, they will chase a female-scented male just as doggedly. But when Donlea put the naïve males to sleep for four hours right after their experience, they retained a memory of it. These well-rested males didn’t bother trying to mate with scented males the second time around. Flies only remembered their humbling experience when they actually slept—activating the fan body but keeping the flies awake produced no memory. Activating the ellipsoid body also made no difference to memory.
The researchers have not yet figured out the mechanism by which activating the fan body causes sleep. Still, their flies should be useful in future studies, researchers said. “One thing that is still missing from the flies is the ability to record, in vivo, from neurons,” said Chiara Cirelli of the University of Wisconsin-Madison. Researchers would like to be able to perform live imaging and electrophysiology on the brain during sleep. But fly brains and neurons are so minute that even the tiniest electrode is quite invasive, and “not conducive to deep sleep,” Cirelli noted. But she and Shaw suspect that being able to activate sleep with temperature will help flies sleep even with an electrode in their brains.—Amber Dance.
More musings from a maniac:
"Just like what Nazi Germany did to the Jews, so liberal America is now doing to the evangelical Christians. It's no different. It is the same thing. It is happening all over again. It is the Democratic Congress, the liberal-based media and the homosexuals who want to destroy the Christians. Wholesale abuse and discrimination and the worst bigotry directed toward any group in America today. More terrible than anything suffered by any minority in history." –Pat Robertson
Ombow-The Beast is probably just a mentality, stemming from intolerance and transcending into violence (or creating fear and paranoia which results in undue and irrational violence, based on deluded ideology). On the other hand, if the Beast is a living, breathing entity, I agree with you, it will disguise itself as Godlike, or a devoted follower of God. Which brings me to Pat Robertson, who I consider a good candidate for the title of Beast:
Pat Robertson Says Gay Marriage Will Bring The Wrath Of God
BY ON TOP MAGAZINE STAFF
PUBLISHED: JUNE 28, 2011
Televangelist Pat Robertson on Monday warned viewers of The 700 Club that gay marriage will bring the wrath of God.
The 81-year-old Christian conservative made his remarks after a segment on New York becoming the sixth – and most populous – state to legalize marriage for gay and lesbian couples.
“I think we need to remember the term sodomy came from a town known as Sodom, and Sodom was destroyed by God Almighty and the thing that they practiced was homosexual activity and even they tried to rape angels who came down there, so that's the kind of people they were,” Robertson said. “But beyond that, Jesus when He spoke of Sodom He didn't say anything about the homosexuality he talked about just the fact that business was as usual until God decided to destroy it. And He sent an angel down there and He said to Lot and his family, 'get out now because I’m gonna destroy this whole area.' That's where sodomy came from, we use the term sodomy and it means Sodom. What's it like? We're heading that way as a nation. In history there's never been a civilization ever in history that has embraced homosexuality and turned away from traditional fidelity, traditional marriage, traditional child-rearing, and has survived. There isn't one single civilization that has survived that openly embraced homosexuality. So you say, 'What’s going to happen to America?' Well if history is any guide, the same thing's going to happen to us.”
Theologians, however, are not uniformly in agreement that the sin of Sodom was homosexuality. Many, if not most, explain that Sodom's sin was instead neglect of needy travelers.
“It's not a pretty world we live in right now,” Robertson added, “and we need all of God's help we can get. And I don't think we are not exactly setting ourselves up for his favor.”
If they can't unlock the potential of ampakines as a novel drug to restore breathing in opiate and barb. induced RD without reversing analgesic affects, I don't expect too much from placing SA as the lead engine. Get a bona fide mgmt team in the cab and my opinion would be revised.
The greatest failure of these underachievers is that they can't acknowledge or adapt to any of their many little failures.
And it only took 10 years to realize this.
Over-the-Counter Drug for Insomnia & Incontinence Can Kill
MyHealthNewsDaily Staff
Date: 24 June 2011 Time: 06:16 PM ET
Common over-the counter and prescription medications known as anticholinergics can cause cognitive impairment and can lead to death, a new study says.
The group includes over-the-counter products containing diphenhydramine, prescription sleep aids and incontinence treatments, many of which are frequently taken by older adults, the researchers said.
"Physicians should review with older patients all the over-the-counter and prescription drugs they are taking to determine exposure," said study researcher Dr. Malaz Boustani, an associate professor and aging researcher at Indiana University School of Medicine.
Older adults and cognitive function
The two-year study looked at the affect of these medications on 13,000 men and women age 65, and is part of a larger United Kingdom-based study looking at health and cognitive function in older adults.
Anticholinergics affect the brain by blocking the neurotransmitter acetylcholine.
The drugs include over-the-counter medications such as those sold under the brand names Benadryl, Dramamine, Excedrin PM, Nytol, Sominex, Tylenol PM and Unisom, the researchers said. Other anticholinergic drugs, such as Paxil, Detrol, Demerol and Elavil are available by prescription.
Medications with anticholinergic effects are used for many diseases, including hypertension and congestive heart failure. The study found that those who were older, had lower incomes and a greater number of health conditions were more likely to use these medications. Women were more likely to report taking anticholinergic medications, due to the greater number of health conditions reported by women than by men.
More work needed
"We looked at drugs with either moderate [or] severe anticholinergic activity. After adjusting for age, sex, baseline mental status, education, income level, number of non-anticholinergic medications and health conditions, we found that taking anticholinergic medications was linked to cognitive impairment and for the first time to death," said study researcher Dr. Chris Fox, a psychiatrist at the University of East Anglia.
"We need follow-up to determine the degree to which anticholinergics are being prescribed for diseases with significant risk of death and the impact of that on our findings," Fox said.
The study was published online today (June 24) in the Journal of the American Geriatrics Society.
Gfp-The Beast has been here all along: It's the Gay movement. What we see as good humor or equal rights, the weirdo-worshippers see as the anti-christ, the great floods coming, the rapture...or just pure sacrilege! I still have love for you Ombow, but you need to face the tolerant God.
Ps. Love the Letterman/Martin clip, and the Diaz/Applegate clip.
I've met Letterman at One Rockefellar Center, and walked past Cameron Diaz on the sidewalk off Brickell Ave. in Miami, when she was filming Something About Mary (Her office in the movie was one floor above where I was working at the time, with the same view)--it was just her and I on the sidewalk, and she was pacing and talking on the cell, I believe with Matt Dillon, when we crossed paths. Steve Martin is probably one of my favorite movie/tv comedian actors (The Jerk; Planes Trains and Automobiles, were probably my favorite of his, along with his SNL credits). Applegate, too, has had a storied career since her earlier, slutty years :)
Bring some of that luck over here. With you buying ICGN at a comparable market cap to Corx (albeit, with far, far, far, fewer shares), you can certainly funnel some of those proceeds/raindrops (and good fortune) on this dried up Cortex Cactus(even the thorns are brittle, brown, and weak or non-existent). Could be a good time to accumulate, or maybe this is the time that your luck changes (and the drought remains for us, over here in never never land...).
The damage control patrol seems to have ceased operation, it may be time to buy. Look and hope for the science to prevail over mgmt.
Good news (particularly because it results in religious fanatics coming out of the closet, and it's good to know who you're dealing with in passing judgement. The more people tweet away or draw public attention, the more they reveal about themselves....):
NY Legislature legalizes gay marriage
By MICHAEL GORMLEY, Associated Press – 14 mins ago
ALBANY, N.Y. – New York lawmakers narrowly voted to legalize same-sex marriage Friday, handing activists a breakthrough victory in the state where the gay rights movement was born.
New York will become the sixth state where gay couples can wed and the biggest by far.
"We are leaders and we join other proud states that recognize our families and the battle will now go on in other states," said Sen. Thomas Duane, a Democrat.
Gay rights advocates are hoping the vote will galvanize the movement around the country and help it regain momentum after an almost identical bill was defeated here in 2009 and similar measures failed in 2010 in New Jersey and this year in Maryland and Rhode Island.
Though New York is a relative latecomer in allowing gay marriage, it is considered an important prize for advocates, given the state's size and New York City's international stature and its role as the birthplace of the gay rights movement, which is considered to have started with the Stonewall riots in Greenwich Village in 1969.
The New York bill cleared the Republican-controlled state Senate on a 33-29 vote. The Democrat-led Assembly, which passed a different version last week, is expected to pass the new version with stronger religious exemptions and Democratic Gov. Andrew Cuomo, who campaigned on the issue last year, has promised to sign it. Same-sex couples can begin marrying begin 30 days after that.
The passage of New York's legislation was made possible by two Republican senators who had been undecided.
Sen. Stephen Saland voted against a similar bill in 2009, helping kill the measure and dealing a blow to the national gay rights movement.
"While I understand that my vote will disappoint many, I also know my vote is a vote of conscience," Saland said in a statement to The Associated Press before the vote. "I am doing the right thing in voting to support marriage equality."
Gay couples in gallery wept during Saland's speech.
Sen. Mark Grisanti, a GOP freshman from Buffalo, also said he would vote for the bill. Grisanti said he could not deny anyone what he called basic rights.
The effects of the law could be felt well beyond New York: Unlike Massachusetts, which pioneered gay marriage in 2004, New York has no residency requirement for obtaining a marriage license, meaning the state could become a magnet for gay couples across the country who want to have a wedding in Central Park, the Hamptons, the romantic Hudson Valley or that honeymoon hot spot of yore, Niagara Falls.
New York, the nation's third most populous state, will join Connecticut, Iowa, Massachusetts, New Hampshire, Vermont and Washington, D.C., in allowing same-sex couples to wed.
For five months in 2008, gay marriage was legal in California, the biggest state in population, and 18,000 same-sex couples rushed to tie the knot there before voters overturned the state Supreme Court ruling that allowed the practice. The constitutionality of California's ban is now before a federal appeals court.
While court challenges in New York are all but certain, the state — unlike California — makes it difficult for the voters to repeal laws at the ballot box. Changing the law would require a constitutional convention, a long, drawn-out process.
The sticking point over the past few days: Republican demands for stronger legal protections for religious groups that fear they will be hit with discrimination lawsuits if they refuse to allow their facilities to be used for gay weddings.
The climactic vote came after more than a week of stop-and-start negotiations, rumors, closed-door meetings and frustration on the part of advocates. Online discussions took on a nasty turn with insults and vulgarities peppering the screens of opponents and supporters alike and security was beefed up in the capitol to give senators easier passage to and from their conference room.
The night before, President Barack Obama encouraged lawmakers to support gay rights during a fundraiser with New York City's gay community. The vote also is sure to charge up annual gay pride events this weekend, culminating with parades Sunday in New York City, San Francisco and other cities.
Despite New York City's liberal Democratic politics and large and vocal gay community, previous efforts to legalize same-sex marriage failed over the past several years, in part because the rest of the state is more conservative than the city.
The bill's success this time reflected the powerful support of Cuomo and perhaps a change in public attitudes. Opinion polls for the first time are showing majority support for same-sex marriage, and Congress recently repealed the "don't ask, don't tell" policy that barred gays from serving openly in the military.
In the week leading up to the vote in New York, some Republicans who opposed the bill in 2009 came forward to say they were supporting it for reasons of conscience and a duty to ensure civil rights.
Pressure to vote for gay marriage also came from celebrities, athletes and New York City Mayor Michael Bloomberg, the Republican-turned-independent who has long used his own fortune to help bankroll GOP campaigns and who personally lobbied some undecided lawmakers. Lady Gaga has been urging her 11 million Twitter followers to call New York senators in support of the bill.
While the support of the Assembly was never in doubt, it took days of furious deal-making to secure two Republican votes needed for passage in the closely divided Senate.
Representatives of the Roman Catholic Church, Orthodox rabbis and other conservative religious leaders fought the measure, and their GOP allies pressed hard for stronger legal protections for religious organizations.
Each side of the debate was funded by more than $1 million from national and state advocates who waged media blitzes and promised campaign cash for lawmakers who sided with them.
But GOP senators said it was Cuomo's passionate appeals in the governor's mansion on Monday night and in closed-door, individual meetings that were perhaps most persuasive.
The bill makes New York only the third state, after Vermont and New Hampshire, to legalize marriage through a legislative act and without being forced to do so by a court.
___
Associated Press writer Michael Virtanen contributed to this report.
More bigotry running amok:
Southwest suspended pilot after radio rant
– Wed Jun 22, 4:15 pm ET
DALLAS – Southwest Airlines Co. suspended a pilot whose disparaging comments about gays and older flight attendants were transmitted over an air-traffic control frequency.
The pilot was talking with another crew member and apparently didn't realize that his microphone was on.
Southwest said Wednesday that the pilot was reinstated after going through diversity training. The incident happened in March and was reported this week by KPRC-TV in Houston.
On a tape of the two-and-a-half minute rant, the pilot can be heard talking about wanting to socialize with co-workers but complaining that many were gay or too old or too heavy. Sometimes using profanity and slurs, he called them "a continuous stream of gays and grannies and grandes." An air-traffic controller in Houston told pilots in the area to check if their microphone was stuck open.
"The actions of this pilot are, without question, inconsistent with the professional behavior and overall respect that we require from our employees," said Southwest spokeswoman Brandy King. She said the pilot was reprimanded and suspended without pay, although she wouldn't say for how long. She said he apologized to air-traffic controllers and their bosses.
King declined to identify the pilot. She said he has worked for Southwest for more than a dozen years and has an otherwise good record.
The Federal Aviation Administration said it alerted Southwest after determining that the pilot on the tape was likely from Southwest.
FAA spokesman Lynn Lunsford said the incident occurred at a time in the flight when personal conversions are allowed in the cockpit but that the FAA "expects a higher level of professionalism from flight crews."
Edit: In that case, the word 'marriage' is meaningless, and by your interpretation of God's word; God is meaningless, religion is meaningless, and morality is meaningless...except to you and similar fanatics...
Maybe you're gay but practicing sexual abstinence, lol. Maybe you had an 'experience' in your trippin' days. Pray tell...
Pure ignorance, ombow. I'm just calling a spade and spade...
If you aren't or haven't been 'gay', it will come as a big surprise to you, how similar you probably are to 'queers,' as you say. You, for instance, are probably overweight, therefore you've suffered similar ridiculing. You also probably haven't procreated, which is a Homo MO. I'm sure you can think of plenty other similarities, such as closeness to Mom, sensitivity, colorful dress (tie-dyes), delusions of grandeur...
I was with you entirely, except for this remark:
Fool you once, shame on them; fool you twice, shame on you.
Talking Deals; Small Companies Try a Partnership
By Lawrence M. Fisher
Published: January 9, 1992
Correction Appended
SAN FRANCISCO— WHEN science-rich but cash-poor biotechnology companies go looking for a savior with deep pockets, they usually turn to one of the giant drug concerns. Cortex Pharmaceuticals Inc., a start-up company focusing on products for treating brain diseases, tried that route at first, but found a better match with a company its own size.
This week Cortex, based in Irvine, Calif., announced a collaborative agreement with Alkermes Inc., a four-year-old company in Cambridge, Mass., that is developing technology to enable drugs to enter the brain more easily. The two companies will co-develop compounds that Cortex is now working on that are believed to counteract the destruction of nerve cells that accompanies strokes. Alkermes will also make a series of investments in Cortex, which could ultimately total as much as $26.5 million.
Cortex's management knew it could not afford to develop the compounds into drug form and bring the drug to market alone, and began looking for possible partners among the large pharmaceutical companies. But after nine months of meetings with several candidates, none of which they would name, they became discouraged with the slow pace and bureaucracy of those concerns. In contrast, the deal with Alkermes came together in just one month.
"I think we fell in love with each other very quickly, began dating intensely and were married soon after," said Raymond T. Bartus, Cortex's executive vice president for research and development and chief operating officer. "Alkermes is very aggressive," he said, noting the rapid progress Alkermes has made moving its own product into human clinical trials.
Another attraction is that a single successful drug will have the same relative importance to both companies. "Having spent 15 years in large pharmaceuticals companies, I greatly appreciate the net value of working with another small company," Dr. Bartus said. "The net value of a success here is not diluted for either of us. The worst thing we could have done is to do a deal where our first-born wasn't treated with the utmost importance."
For Alkermes, which is developing drug-delivery technologies rather than drugs, Cortex presented an opportunity to acquire a drug candidate at an early stage to which that technology can be applied. Although itself a young company, Alkermes has both more capital, as the result of two successful public offerings last year, and more experience taking a product through development into clinical trials.
"If you think of us as being a company building a significant development capability, the smart thing to do is to pump products through it," said Richard F. Pops, president and chief executive of Alkermes. "It is a huge commitment for a company to make, to take a drug from a bench-level lead to a drug in a vial that you can actually inject in a patient."
The collaboration will focus on three classes of enzyme inhibitors discovered by Cortex. They block the action of calpain, an enzyme that appears to be responsible for the destruction of nerve cells after the brain is temporarily deprived of blood, as during a stroke or heart attack. The action of calpain follows the stroke by several hours, providing an opportunity to administer a drug that blocks it.
Under the terms of the agreement, Alkermes will provide $2 million to Cortex in research and development funds this year and an additional $2.5 million in 1993. As products of the collaboration proceed through clinical trials, Cortex will receive up to $10 million in payments tied to passing various hurdles in testing and regulatory review. The agreement gives Alkermes worldwide, exclusive rights to make and market any products resulting from the collaboration; Cortex will receive royalties on sales.
In a related transaction, Alkermes purchased 750,000 newly issued shares of Cortex's common stock for $1.5 million, and warrants to purchase an additional two million shares of common stock -- one million shares at $3 each and another million at $7.50 each. Cortex shares closed yesterday at $3.75, up $1.5625 a share, in over-the-counter trading; Alkermes shares closed at $27, up $4.75 a share.
One reason Cortex decided on the partnership was that its relatively low stock price precluded doing a secondary public offering during the bull market for biotechnology stocks in recent months. Cortex went public several years ago, at a relatively early point in its history, which has limited its subsequent ability to raise capital. Alkermes waited longer, and was able to go public last year at a more favorable stock valuation.
"The check that we write today is very, very manageable, given our balance sheet," Mr. Pops said, noting that Alkermes has about $56 million.
Correction: January 10, 1992, Friday Because of an editing error, the Talking Deals column in Business Day yesterday, about a partnership between biotechnology companies, misstated the Wednesday stock performance of Alkermes Inc. in some editions. The stock closed up $4.75, to $27 a share, in over-the-counter trading. The column also ended with an incomplete sentence in some editions. It should have read: " 'The check that we write today is very, very manageable, given our balance sheet,' Mr. Pops said, noting that Alkermes has about $56 million in cash.
Happy Father's Day to Doc Stoll. The 'Father of Failure' graced himself with $180K in bonuses between '08 and '09. Vintage years they were for the share price, vintage indeed. Well deserved, just like your new title on this special day. But why no bonus last year? Why no options this year, in conjunction with the unaffiliated BOD members? What the hay, it's only another 30K (options). You're no less worthy now then in '08 and '09? At least your salary increased 33k in '10, compared to '09. 2010 was a very good year for us also, no? I believe we appreciated about 70% from Jan thru Dec. We owe it to you, Daddio! Keep up the good pay:
Name and Principal Position
Roger G. Stoll, Ph.D.
Year Salary Bonus
2010 $ 338,218 — — $ — — $ 338,218
Executive Chairman
2009 $ 305,250 — — $ 93,552 — $ 398,802
2008 $ 370,000 — — $ 87,280 — $ 457,280
Really? 3 weeks of suffering, and you're done? Dude, borrow one play from the Cortex playbook, and you could at least finish out the season (but don't borrow more than that, or you will be caught in a vicious spiral). This is about as lame as 4 years of harrowing losses, although maybe you were being forced out by the Administration. Imagine if our BOD was a smidgen more aggressive -- we would be marginally on the right path at worst, and happy at best:
Marlins' Edwin Rodriguez resigns
Marlins manager Edwin Rodriguez has resigned with the team mired in a nine-game losing streak.
Marlins bench coach Brandon Hyde will replace Rodriguez for Sunday's game against the Rays, the team said in a news release.
The Marlins were 1-17 in June entering the game at Tampa Bay and sat last in the NL East at 32-29, 12½ games behind the Phillies.
Rodriguez became the first Puerto Rican manager in the major leagues when the Marlins made him interim manager last June, and the team went 46-46 the rest of the year. He then spent a month after the regular season in limbo before being named to the permanent job.
The Marlins said they had discussed several managerial candidates with Loria, but they conducted no formal interviews.
Rodriguez received only a one-year contract, but said at the time he figured he still got a good deal.
"I'm very confident that our team, even though it's a very young team, we're going to be winning a lot of games," he said. "Watching the World Series and the way it went has given me more reason to believe we have what it takes."
Information from The Associated Press was used in this report.
Why I'm Upgrading Adolor to a Buy
http://seekingalpha.com/article/275563-why-i-m-upgrading-adolor-to-a-buy?source=yahoo
Investment Thesis
Adolor has gained back Glaxo’s (GSK) rights to Entereg (alvimopan) in a transaction that I regard as a highly positive, company changing event. Entereg has the critical sales mass to enable Adolor to be a self-sufficient, cash flow positive company. I believe that the Entereg sales run rate entering 2012 could be on the order of $40 million, $50 million entering 2013, and over the next several years could grow to $100 million.
The terms of the deal were amazingly favorable to Adolor, and the company has much for which to thank Glaxo. On its own, Adolor could not have brought Entereg to this sales level and might not have been able to launch it in the first place. The difficulties of introducing a first-in-class drug to an increasingly cost-conscious hospital marketplace has made the launch and sales ramp of a new product much more difficult, and it can be prohibitively expensive for a small company. Hiring and training a sales force, and then going through the time consuming process of gaining formulary acceptance and implementing the REMS program which was required for Entereg, is something that Adolor could probably not have done on its own. Now after three years of heavy lifting Glaxo is handing this very valuable asset to Adolor on a cheaply bought silver platter.
Based on Entereg potential alone, Adolor is a very interesting company. The patent position of the product is expected to extend protection from generics until 2020. One way of estimating its value is to estimate a multiple of enterprise value to sales based on what comparable companies sell for. Because of its strong patent position, I think that either the stock market or a potential acquirer might value Entereg at a multiplier of 3.0 to 3.5 times (or possibly higher). Appyling the 3.0 to 3.5 multiplier to my year-end 2011 sales run rate estimate of about $40 million results in a potential market capitalization of $120 to $140 million, or a stock price potential of $2.57 to $3.00 per share. This compares to the current stock price of $1.60.
While the above scenario addresses the potential value of Entereg, it does not attribute any value to the sales force that Entereg supports. This sales force provides additional value in that it allows Adolor to acquire or co-promote additional products. Over time, I could argue that the financial leverage of the sales force might have value approaching that of Entereg. Of course, there are so many unknowns that I can’t easily assign a value to this proprietary sales force. I just know that there is substantial value.
Adolor is fast approaching a binary clinical trial event that can significantly impact the investment outlook. The company is developing a new opioid induced constipation product called ADL 5945, and the results of a key phase II trial will be reported in 3Q, 2011. The company would prefer to partner ADL 5945, as the anticipated development cost of around $50 million is probably too much for Adolor to assume on its own. It is not possible for me to predict how positive the results might be-- or even if they will be successful. Investors must be prepared for either a success or failure scenario. Partnering the product-- even with successful phase II results-- is also not a given.
If the trial is reasonably successful, it can only be perceived as adding value and therefore maintaining or increasing the stock price. However, if the trial fails and ADL 5945 is abandoned, there remains an interesting scenario for 2012. As shown later in this report, I am estimating Entereg sales of $45 million in 2012. In the unlikely event that company were to decide to fund all future development of ADL 5945, it might spend about $30 million on R&D, leading to an operating loss of $26 million in 2012. A partnering deal could reduce this amount of R&D spend. If ADL 5945 fails, it is likely that the R&D spend could drop, perhaps to as low as $5 million. Based on my $45 million sales estimate for Entereg in 2012 this could produce an operating loss of $515,000 and EPS of $0.00. For investors, it would highlight the value of Entereg.
The third factor to consider in looking at Adolor is the potential that the company might do a financing regardless of ADL 5945 success or failure. The company ended the first quarter of 2011 with $39.3 million of cash. Assuming quarterly burn rates of $7.0 million in 2Q, 2011, $5.0 million in 3Q, 2011 $6.0 million in 4Q, 2011 and the $2.5 million payment to Glaxo, the company could end the year with $18.8 million of cash. Although it is not a certainty that the company will have to raise cash, it is a possibility that worries some investors.
I think the concern about financing is impacting the stock at this time, so let’s examine the possibilities. If the trial results of ADL 5945 are sufficiently positive to allow a partnering deal, the upfront payment could alleviate the need for any new equity offering. Nektar (NKTR) received an upfront payment of $125 million from Astra Zeneca (AZN) over one year ago for a drug similar to ADL 5945 that was just coming off of positive phase II results. If Adolor could strike a deal with an upfront of just $25 million or higher, it would probably obviate the need for an equity raise.
If ADL 5945 fails, Adolor might be able to avoid an equity offering, but there would be some financial brinksmanship involved. However, I think the company would easily qualify for a debt financing given the predictable cash flow of Entereg. This might allow the company to avoid an equity offering altogether, or to do a much smaller one.
My fundamental judgment is that the intrinsic value of Entereg offsets the risk of the ADL 5945 trial failing or the potential for an equity offering, and so I regard the stock as attractive whether or not the ADL 5945 trial is successful. However, I acknowledge that there remains the headline risk that news of the trial failure or of an equity offering could cause a decline from the current price. I am recommending purchase, but there is a chance that the stock could decline on unfavorable headline news before it meets my expectation of going higher.
Adolor Gains Glaxo’s Rights to Entereg
Adolor has entered into an agreement to acquire Glaxo’s ownership share of Entereg. The two companies have been co-promoting Entereg on a profit / loss sharing basis since its introduction in 3Q 2008. Adolor will pay Glaxo $25 million spread over six years, with the initial payment of $2.5 million payable upon closing the transaction in September of 2011. I assume that none of the subsequent six annual payments will exceed $4.0 million. There may also be a payment of $15 million dependent upon the achievement of certain sales milestones, but this will be some years off. Adolor will also pay Glaxo a mid-single digit royalty on sales that will increase with sales levels.
The initial focus of the Entereg launch was on gaining hospital registration for the REMS program, hospital formulary approval and educating the hospital staff about the product’s attributes. Being first in class and first to market is not an easy road. The early years of a product launch in the hospital marketplace are a daunting challenge. Adolor is acquiring Glaxo’s rights to Entereg after most of the heavy lifting has been done.
Entereg sales were at a run rate of $30 million in the first quarter of 2011 and I believe that run rate entering 2012 will be about $40 million. The previously expressed long term goal is to grow Entereg sales to a level of $100 million. With this new arrangement, management expects that Entereg will contribute meaningful cash flow in year one and into the future. Allowing for the royalty payment to Glaxo, the product contribution to sales in 2012 could be on the order of 30% and longer term it could reach 50%. The new Glaxo arrangement will be accretive over the next year.
The Transition of Entereg to the Adolor Sales Force
The hospital market is focused on post-operative care pathways more than ever, and in particular, length of stay; this is the raison d’etre for Entereg. There has been a continual string of studies done by third party physicians and hospitals that conclude that Entereg can meaningfully shorten length of stay for bowel resection patients. The market place should be increasingly receptive to Entereg.
Adolor has always played an active role and is up to the challenge of taking over marketing Entereg. The NDA approval was obtained by Adolor and they also ran the clinical trial program that led to that approval. They have also managed pharmaco-vigilance programs, administered the REMS program and have driven medical affairs initiatives. Adolor has also been responsible for manufacturing and has led the marketing effort since launch.
The major change going forward will be on detailing. Whereas Adolor has been detailing alongside Glaxo, they will now be solely responsible. The expansion of the sales force is the largest part of this transitional effort, but it is a relatively straightforward process. Up to now, the Adolor account managers have been working alongside the Glaxo account managers in large metropolitan areas where Entereg is being used in several hospitals. It is believed that increased promotional effort will have the greatest impact in this account base. This is based on the premise that your best new customer for Entereg is the best current customer. The current Adolor account managers will remain in their current account geographies. New reps will be added in geographies which were previously only covered by Glaxo representatives.
The company has already started the process to double the size of the field force to 50. They expect to have the sales personnel trained and calling on customers by September 1. The new account structure will be optimized to cover the vast majority of existing customers. Adolor is also planning to increase investment in non-personnel promotional efforts for existing accounts that will not initially be covered by Adolor account managers.
The target list of hospitals that perform 80% of bowel resection procedures in the U.S. is 1600. Adolor currently has 25 people in the field that layer on top of the Glaxo national sales force. The Adolor / Glaxo strategy up to now has been focused on “same store sales” growth in key existing accounts. Over 70% of the targeted 1600 accounts are registered in the EASE program and 50% either have added Entereg to their formularies or otherwise have made Entereg available to their surgeons. There is much growth potential in exisitng accounts, and importantly, they have passed use hurdles and formulary access.
Adolor will also be taking over physical distribution of Entereg and the contracts with GPOs, federal accounts, wholesalers and hospital systems by September 1. Distribution will be largely a turnkey transition using an established third party logistics company that has a proven distribution platform.
On a full time employee basis, management believes that the new Adolor sales force will be nearly identical in account impact to the former combined Adolor / Glaxo sales force. Each Adolor employee will spend 100% of their time on promoting Entereg, as opposed to Glaxo reps who had to focus on a number of other products. Adolor believes that increased productivity in the smaller sales force will compensate for the smaller head count.
Financial Impact of the Entereg Deal
This deal has lowered the bar to cash flow breakeven. Management now believes that the company could reach breakeven somewhere in the area of $40 to $45 million of Entereg sales. However, this excludes expenses for the potential phase III program of ADL 5945.
Sales and Earnings Model for Adolor if the Company Decides to Fund All ADL 5945 Development
FY 2008 FY 2009 FY 2010 FY 2011 FY 2012 FY 2013
Revenues:
Product sales, net 1,247,271 14,609,022 25,386,285 35,671,286 45,000,000 54,000,000
Contract revenues 48,208,224 22,751,584 17,916,233 4,738,944 0 0
Total revenues, net 49,455,495 37,360,606 43,302,518 40,410,230 45,000,000 54,000,000
Operating expenses incurred:
Cost of product sales 203,972 1,515,073 2,876,503 5,146,076 7,515,000 9,018,000
Research and development 52,664,213 43,930,303 33,210,404 26,251,146 30,000,000 32,000,000
Selling, general and administrative 31,114,718 36,947,749 34,053,247 34,197,318 33,000,000 35,000,000
Restructuring charge 0 3,932,582 1,918,701 0 0 0
Total operating expenses 83,982,903 86,325,707 72,058,855 65,594,540 70,515,000 76,018,000
Loss from operations (34,527,408) (48,965,101) (28,756,337) (25,184,310) (25,515,000) (22,018,000)
Non-operating income 4,405,148 1,050,787 1,482,269 476,514 450,000 400,000
Net loss (30,122,260) (47,914,314) (27,274,068) (24,707,796) (25,065,000) (21,618,000)
Basic and diluted net loss per share ($0.65) ($1.03) ($0.59) ($0.53) ($0.53) ($0.45)
Basic and diluted shares 46,158,458 46,296,235 46,338,538 46,738,381 47,205,765 47,677,822
This next model presents a very different scenario in which I assume that ADL 5945 development is abandoned, and the company is based exclusively on Entereg.
Sales and Earnings Model for Adolor if the ADL 5945 Development is Abandoned
FY 2008 FY 2009 FY 2010 FY 2011 FY 2012 FY 2013
Revenues:
Product sales, net 1,247,271 14,609,022 25,386,285 35,671,286 45,000,000 54,000,000
Contract revenues 48,208,224 22,751,584 17,916,233 4,738,944 0 0
Total revenues, net 49,455,495 37,360,606 43,302,518 40,410,230 45,000,000 54,000,000
Operating expenses incurred:
Cost of product sales 203,972 1,515,073 2,876,503 5,146,076 7,515,000 9,018,000
Research and development 52,664,213 43,930,303 33,210,404 26,251,146 5,000,000 7,000,000
Selling, general and administrative 31,114,718 36,947,749 34,053,247 34,197,318 33,000,000 35,000,000
Restructuring charge 0 3,932,582 1,918,701 0 0 0
Total operating expenses 83,982,903 86,325,707 72,058,855 65,594,540 45,515,000 51,018,000
Loss from operations (34,527,408) (48,965,101) (28,756,337) (25,184,310) (515,000) 2,982,000
Non-operating income 4,405,148 1,050,787 1,482,269 476,514 450,000 400,000
Net loss (30,122,260) (47,914,314) (27,274,068) (24,707,796) (65,000) 3,382,000
Basic and diluted net loss per share ($0.65) ($1.03) ($0.59) ($0.53) ($0.00) $0.07
Basic and diluted shares 46,158,458 46,296,235 46,338,538 46,738,381 47,205,765
Neuro accused me of being masochistic. Clearly, I'm not the only one. If you are reading this, chances are, you are in the same club. Guest of honor tonight...management...welcome to your club...
Common sense of reality. I should trademark that :)
Not an evening post since June 14th -- 4 days ago? Everyone is speechless, yet I've been asking mgmt to shut me up for over 4 years, to no avail. Actions speak louder than words of wisdom. From mgmt, we have neither...
Clarence Clemons dead at age of 69
By Jonathan Tully June 18, 2011
Rolling Stone and several other news sources are reporting that Clarence Clemons, the longtime legendary sax player for Bruce Springsteen’s E Street Band, has died at the age of 69.
Mr. Clemons, who made his residence on Singer Island, suffered a stroke on June 12. Initial reports said he was showing signs of improvement, but Rolling Stone reported that he had taken a turn for the worse late in the week.
Mr. Clemons was known as the Big Man in the E Street Band and his sax has been one of the most defining elements of the band’s sound. He has suffered from numerous ailments over the last few years. He had double knee surgery and even had to perform from a wheelchair at one point.
But his health seemed to be improving. Just last month, he performed with Lady Gaga on the season finale of “American Idol.”
Mr. Clemons joined Springsteen’s group in 1971 — Rolling Stone wrote that the initial meeting between Mr. Clemons and Springsteen took on mythical qualities, that the initial meeting between the singer-songwriter and the ex-football player who could play a great sax was on a powerfully rainy night in Asbury Park, N.J.
Whatever the circumstances, Mr. Clemons’ sax left an indelible stamp on Springsteen’s greatest hits. As Ben Sisario wrote in the New York Times, “Mr. Clemons played a central part in Mr. Springsteen’s music, complementing the group’s electric guitar and driving rhythms in songs like ‘Born to Run’ and ‘Tenth Avenue Freeze-Out’ with muscular, melodic saxophone hooks that echoed doo-wop, soul and early rock ’n’ roll.”
Mr. Clemons’ work was known over several generations — not only did he perform with Lady Gaga, but is also featured on her new single, “The Edge of Glory”, and appears in the video.
Locally, Mr. Clemons was known for his work with many charities. He has been an advocate for Home Safe, which aids abused and neglected children, and as recently as March had put together two different events in which he raised more than $70,000.
That too, will not pan out. It's just more God fearing mumbo jumbo, like the rapture.
Judge: Scripps scientist told lies
By JEFF OSTROWSKI
Palm Beach Post Staff Writer
Friday, June 17, 2011
JUPITER — A Scripps Florida cancer researcher has been barred from receiving federal research grants for three years because, investigators say, he published bogus data in scientific journals before he joined Scripps.
Philippe Bois, 40, an assistant professor in the department of cancer biology at Scripps Florida, "knowingly and intentionally falsified data" that appeared in articles in 2005 in The Journal of Cell Biology and Molecular and Cellular Biology, the U.S. Department of Health and Human Services' Office of Research Integrity said last week .
Bois disputes the finding and intends to appeal, The Scripps Research Institute said in a prepared statement. Bois declined to comment.
Bois was a postdoctoral fellow at St. Jude Children's Research Hospital in Memphis when he conducted the research cited by federal investigators. He joined Scripps Florida in 2007.
"In publishing incomplete and inaccurate articles, Respondent Bois committed serious scientific misconduct," Administrative Law Judge Carolyn Cozad Hughes wrote in a May decision.
A National Institutes of Health spokeswoman said it's unclear how last week's finding will affect federal funding for two projects Bois is working on at Scripps Florida. Bois is the principal investigator on two projects funded by NIH - one a $291,750 grant that ends in August, the other a $320,760 grant for work through 2015.
NIH grants are the lifeblood of scientific research in the United States, and they're one of the performance measures that a state oversight board tracks as it monitors taxpayers' investment in Scripps Florida. The institute won $35 million in NIH grants in 2010.
The article in the Journal of Cell Biology was co-authored by Bois and five other scientists, including John Cleveland, now chairman of Scripps Florida's department of cancer biology.
For that article, Bois conducted two 2003 experiments into a protein's effect on certain types of childhood tumors. Only one of the two experiments supported Bois' hypothesis that a malfunction of the FOXO1a gene led to soft-tissue cancer, and he didn't report the experiment that didn't favor his theory, Cozad Hughes wrote.
Bois said a second experiment supported his theory, but there are no lab records to document the findings and the lab couldn't reproduce the results, the judge wrote.
The Journal of Cell Biology retracted the article in 2007, but not before it was cited seven times by other scientists.
"His colleagues in the scientific world studied and were ultimately misled by its contents, causing further waste of time and resources," Cozad Hughes wrote.
The article in Molecular and Cellular Biology was written by Bois and three other scientists, including Tina Izard, Bois' wife and now an associate professor in Scripps Florida's department of cancer biology.
For that article, Bois altered an image that appeared in the journal, then blamed a graduate student, the Office of Research Integrity said. Molecular and Cellular Biology issued a correction in 2007.
Cozad Hughes wrote that Bois described his mistakes as "honest errors" rather than intentional lies but rejected his argument.
A finding of research misconduct can lead to disciplinary action by a scientist's employer and suspension of federal grants, NIH said. Scripps wouldn't say whether any action has been taken against Bois.
Can Diet Influence Alzheimer’s Disease Biomarkers?
17 June 2011. You are what you eat, the old saying goes. This may be particularly true for the brain. In the June Archives of Neurology, researchers led by Suzanne Craft at the Veterans Affairs, Puget Sound, Washington, present new evidence that a healthy diet may help keep brains young and reduce the risk of Alzheimer’s disease. In a study of about 50 elderly volunteers who ate a diet low in saturated fats and simple sugars, or a high-saturated fat, high-sugar diet, for a month, the researchers saw significant and opposing changes in several cerebrospinal fluid (CSF) biomarkers, including dramatic changes in Aß42. Intriguingly, levels of this AD biomarker moved in different directions depending on whether the participants were cognitively healthy or impaired, which Craft suggests might reflect the underlying state of Aß in the brain. Participants who ate the healthy diet also scored better on a visual memory test than they had at baseline, while participants who ate the unhealthy diet performed more poorly than before. Although many questions remain about exactly how diet affects brain chemistry, these data add to the evidence that people can exercise some control over their cognitive destiny through lifestyle choices.
“I was surprised to see significant biomarker movement in a study with so few people and with treatment for such a short amount of time,” said Anne Fagan at Washington University in St. Louis, Missouri. She was not involved in the study. “I think the results lend credibility to pursuing this line of research further.”
In animal models of AD, high-saturated fat diets are known to accelerate amyloid deposition. In people, epidemiological studies have suggested that a diet low in saturated fats and simple sugars, and high in fruits, vegetables, polyunsaturated fats, and lean proteins may help delay or prevent AD (see, e.g., ARF related news story), but there was little evidence linking diet to changes in AD pathology.
To begin to make this connection, first author Jennifer Bayer-Carter looked at the effect of an intensive diet intervention on CSF biomarkers. Bayer-Carter and colleagues provided all food for four weeks to the participants, who consisted of 20 healthy elderly volunteers and about 30 elderly people with amnestic mild cognitive impairment (aMCI). The volunteers were randomly assigned to eat either a diet that was high in saturated fats and simple sugars, or one that was low in both. The researchers designed the meals to have the same number of calories as the participants normally ate, so weight gain or loss was not a factor. Because the researchers provided all food, they could tightly control the diets, which Craft speculates may be one of the reasons they were able to get significant results over such a short time period. The scientists kept the study short to limit any negative health consequences to participants eating high-saturated fat diets. The researchers collected CSF at the beginning and end of the experiment. Participants fasted for 12 hours before donating CSF, which Craft notes is becoming the standard way to do it, as CSF Aß levels change throughout the day in response to metabolism.
After four weeks, the researchers found numerous statistically significant changes between groups. Several measures of health, such as cholesterol levels and insulin sensitivity, improved in both groups on the healthy diet and worsened in both groups on the unhealthy diet. People with aMCI seemed to be more sensitive to the effects of diet, however, in many cases improving twice as much as the healthy controls on the good diet, and worsening twice as much on the bad diet. This effect did not correlate with any difference in baseline diet or weight between controls and people with aMCI, Craft said; instead, it seemed to be a disease-related vulnerability.
When the researchers looked at AD biomarkers, they saw significant changes in levels of CSF Aß42. Low levels of CSF Aß42 are strongly linked to AD, with the explanation being that as Aß42 clumps into plaques, less of it is available to enter the CSF. In this study, however, the authors found that cognitively normal volunteers had lower levels of CSF Aß42 on the healthy diet, and higher levels on the unhealthy diet. People with aMCI, on the other hand, showed a dramatic increase in CSF Aß42 on the healthy diet, and little change on the unhealthy diet. Although puzzling at first, these seemingly contradictory findings would make sense if concentrations of Aß42 in brain reach a “tipping point” where they begin to form plaques, the authors suggest. Under this hypothesis, cognitively normal people have not yet reached this tipping point, so their brain Aß42 remains soluble and moves easily into the CSF. In that case, CSF Aß42 levels would directly reflect brain levels, and dropping levels could actually indicate better brain health, for example, if the brain is producing less Aß. Cognitively impaired people would be past the tipping point, however, with brain Aß42 already tied up in plaques. The healthy diet may begin to break up plaques, resulting in a rise in CSF Aß42 as the newly soluble peptide is cleared from the brain. This model would go against the conventional wisdom that low CSF Aß is bad news, but scientists contacted for this article found the concept intriguing and worthy of further study.
“This idea of a tipping point is a very interesting hypothesis, and one that is supported by the animal literature,” Fagan said. “A lot of us view low CSF Aß as bad and high CSF Aß as good, but that may not be the case, depending on where in the disease trajectory you are.” Animal studies show that CSF Aß rises until deposits begin to form in the brain, after which the levels drop off. People with Down's syndrome, who accumulate Aß throughout life due to an extra copy of the gene for APP, show a similar pattern of initially high CSF Aß followed by low.
Other AD biomarkers changed on the two diets as well. Lipids known as F2-isoprostanes, which mark neuronal injury, decreased in the CSF after four weeks of healthy eating, but increased in tandem with Aß42 in cognitively normal volunteers eating a poor diet. Levels of the cholesterol chaperone ApoE increased on the healthy diet and decreased on the unhealthy diet. A variant of ApoE is the primary genetic risk factor for sporadic AD. Although scientists do not yet fully understand what ApoE does, the data suggest another mechanism by which diet may affect AD risk, Craft speculated.
Importantly, the two diets also had a functional effect. At the end of the study, people on the healthy diet had improved in a test of delayed visual memory, while the performance of cognitively normal volunteers who ate a high-saturated fat, high-sugar diet worsened. Tests of executive function, motor speed, and other forms of memory showed no change. To find any effect on memory in such a short time period is striking, said Mark Mattson at the National Institute on Aging, Bethesda, Maryland. If the results hold true in future studies, it would suggest that “Your diet can affect your learning and memory, and perhaps your vulnerability to cognitive impairment,” Mattson said. Mattson pointed out that lowering total caloric intake slows down disease and improves memory in AD transgenic mice (see also ARF related news stories on the benefits of caloric reduction in animals [ARF related news story] and humans [ARF news story]). Caloric restriction pumps up levels of brain-derived neurotrophic factor (BDNF), which protects neurons, Mattson said. It would be interesting to compare CSF BDNF levels in people on the high-saturated fat, high-sugar diet with those on the healthy diet, Mattson suggested. Mattson also recommended neuroimaging studies, such as functional MRI and MR spectroscopy, to more directly measure what might be happening in the brains of participants.
Fagan agreed that it would be nice to see more direct measures of brain pathology, for example, amyloid imaging, in people on different diets. “The biggest unresolved issue is, What does the change in CSF Aß42 really reflect?” Fagan said. Amyloid imaging and longer-term studies might help answer this question, she suggested.
Craft agrees. She is particularly interested in what happens to CSF Aß during mid-life, the hypothetical tipping point when Aß starts to deposit in some people’s brains. To answer this, Craft is examining CSF Aß from longitudinal studies on middle-aged adults, and notes that the Dominantly Inherited Alzheimer Network might also be a rich source for such data. In addition, Craft is repeating the diet intervention study in middle-aged volunteers to see if they respond differently from the elderly participants, whose average age was close to 70.
In follow-up studies in both animals and humans, Craft and colleagues will look more closely at the biology that underlies the dietary effects. One possibility is that diet alters ApoE’s efficiency in chaperoning Aß, Craft suggested. A high-saturated fat diet induces insulin resistance, and that may interfere with the brain’s ability to clear ß amyloid as well. Although the mechanisms are not yet clear, “Our study shows in a proof-of-concept manner that a controlled diet intervention can modulate levels of critical markers of AD pathology,” Craft said.
Fagan suggested that it would be interesting to look at the biomarker changes in individual participants in the diet study and see if they correlated with people’s baseline biomarker levels. “Ultimately, people are going to want individualized medicine,” Fagan said. “People will want to know, if my diet changes, what’s the change in my AD risk? We are clearly not there yet.”—Madolyn Bowman Rogers.
Didn't Corx begin their public life with a deal with Alkermes? Maybe the unfortunate, unlucky, unimpressive, and undeserving mgmt team can round out the circle by modifying the poison pill, and selling the skeletal remains to them. Just trying to come up with ideas, after all, the visibility offered by mgmt is as dim and empty as the trading shares (and a fair reflection of mgmt's performance no doubt). Anyway, ALKS has $200m cash, is merging with Elan's drug delivery unit, and will primarily focus on developing drugs that address CNS deficiencies:
Alkermes Intros Study on Depression
Zacks Equity Research, On Friday June 17, 2011, 3:15 pm EDT
Alkermes Inc. (NasdaqGS: ALKS - News) announced initiation of an early-stage study of pipeline candidate ALKS-5461 for treating patients suffering from treatment-resistant depression (TRD). ALKS-5461 is a combination of Alkermes’ another pipeline candidate ALKS-33 (an oral opioid modulator) and buprenorphine.
The multicenter, randomized, double-blind, placebo-controlled trial (n=32) will evaluate the safety and efficacy of ALKS-5461 in patients with major depressive disorder who did not respond adequately to previous antidepressant therapy. Topline data from the trial is expected to be presented in the second half of calendar 2011.
Depression is a chronic and serious disease which affects more than 20 million adults in the US annually. TRD is also known as refractory depression. It is characterized by episodes of depression that are not adequately controlled by standard antidepressant therapy.
Alkermes is also developing ALKS-5461 for treating patients suffering from cocaine addiction. The early stage study is being funded by the National Institute on Drug Abuse (NIDA). In October 2010, Alkermes presented encouraging data from the study.
ALKS-33, a component of ALKS-5461, is currently being studied in mid-stage trials for the treatment of alcohol dependence and other central nervous system disorders. Encouraging data from a trial in alcohol dependent patients was released last year.
A major recent development for Alkermes involves a deal entered into with Elan Corporation (NYSE: ELN - News) in May 2011 to buy the latter’s drug delivery unit (EDT) for $960 million in cash and stock. The deal is expected to close in the third quarter of calendar year 2011. The combined company will be known as Alkermes plc and will be headquartered in Ireland. The merged entity will primarily focus on developing therapies for treating deficiencies of central nervous system. We believe that the transaction is a positive for Alkermes. The deal is expected to boost Alkermes’ cash earnings immediately following its closure. The product portfolio at Alkermes will be strengthened following the merger.
Our Recommendation
Currently we have a ‘Neutral’ long-term recommendation for Alkermes. The company carries a Zacks #3 Rank (‘Hold’ rating) in the short run.
To say Pierre Tran was excited when he left Corx would be an understatement...
Buy on rumor, sell on news. Unless God told you otherwise :)
Don't forget the vet pet theory (vet medicine). I believe that was removed from Stoll's future milestone list, and added to his shit-talking list, along with AD, the FDA letter, the HI partnership babble, 'high morale' blabber, etc.
I think the 'morale' now stands at about $1 mill, lol.
Here's a nice turnaround story (note: it took new mgmt to achieve):
Pacira Raises Wall Street Expectations of a New Blockbuster Painkiller
http://www.xconomy.com/new-york/2011/05/19/pacira-raises-wall-street-expectations-of-a-new-blockbuster-painkiller/
Arlene Weintraub 5/19/11
The last time Xconomy checked in with Pacira Pharmaceuticals (NASDAQ: PCRX), in early 2009, the company was laying off a third of its workforce in the wake of a disappointing clinical trial of Exparel, a treatment for post-surgical pain. Pacira was capital-constrained because the market for life-sciences IPOs was all but dead. And the future was far from certain for the company, which has corporate offices in Parsippany, NJ, and manufacturing and R&D operations in San Diego.
Fast-forward two years and it’s pretty clear Pacira’s fortunes have changed, so much so that the company was able to pull off an IPO in February. Pacira’s executives have been busy presenting data on its pain treatment, most recently at a medical meeting on May 17, when they announced positive results in patients undergoing hemorrhoid surgery. Pacira’s stock is now trading at $10.30—a 47 percent premium to its offering price, and a clear signal that Wall Street fully expects the FDA to approve the pain treatment by its scheduled PDUFA date of July 28.
The main conference room in Pacira‘s Parsippany headquarters bears a sign reading “Exparel War Room”—a fitting description of what the company has been through in the years leading up to, and including, the IPO. “This is the hardest thing I ever did in my life,” declares CEO Dave Stack, a pharmaceutical industry veteran and partner at MPM Capital, who did stints at The Medicines Company, Innovex, and others before being brought in to lead Pacira’s turnaround in 2007.
Pacira was originally DepoTech, a San Diego company that developed a controlled-release drug-delivery technology called DepoFoam. UK-based SkyePharma acquired DepoTech in 1998, but struggled to manage the asset, Stack says, so a syndicate of venture capitalists bought it in 2007 and reformed it as Pacira.
The VCs—MPM, HBM BioVentures, OrbiMed Advisors, and Sanderling Ventures—chose Stack to run Pacira primarily because of his track record. At The Medicine’s Company, Stack and his team developed a marketing plan for the blood thinner bivalirudin (Angiomax) that entailed going into large hospital chains and reviewing the charts of patients who had been given heparin—a cheap and well-accepted alternative to the newer product. Stack and nine cohorts (all of whom are now at Pacira) determined a set of characteristics that could predict which patients were most likely to develop bleeding incidents from heparin that would keep them in the hospital for several extra days. “We wrote algorithms that allowed hospital computers to flag patients” who were most likely to respond badly to heparin, Stack explains. “Then they could say, ‘We should be using Angiomax instead.’”
It worked: bivalirudin turned into a $400 million-a-year product.
Stack has developed a similar plan for marketing Exparel, which is a long-acting version of the pain drug bupivacaine. After major surgeries, bupivacaine is commonly injected into the tissues surrounding the surgical wound. It typically provides pain relief for about eight hours, after which patients are given opioids such as morphine, which can cause serious side effects, particularly in the elderly. Pacira’s formulation of the drug is also injected into the wound, but it provides pain relief for up to three days. That may allow patients to reduce their use of opioids—or better, to bypass them all together.
But Pacira’s quest to convince the FDA that its treatment belongs in the crowded market for pain relievers didn’t go well at first. The agency gave Pacira a choice between doing one placebo-controlled trial or two trials of its formulation vs. regular bupivacaine. The company’s original management team chose the second route—a mistake, Stack says, because the trials didn’t shed enough light on whether the Pacira treatment would reduce opioid use post-surgery.
In the new Phase 3 trial, performed under Stack’s watch, patients undergoing bunion or hemorrhoid surgery were randomized to receive placebo or Exparel, but they were all given the choice of receiving opioids like morphine for pain after their surgeries. The study showed that patients on the Pacira drug consistently waited longer to request additional pain relief—and some never requested opioids at all. In the end, Pacira was able to show that overall opioid use was significantly lower with its treatment in both bunion and hemorrhoid patients.
Pacira went public at $7 a share—significantly below the original target of $12 to $14—but the company eventually found a receptive audience on Wall Street. Jonathan Aschoff, an analyst for Brean Murray Carret & Co. wrote in a March report that even if the company’s pain treatment only captures a small portion of the surgical opportunities, “we consider it a likely event that total revenue will eventually exceed $1 billion.” His price target on the stock is $20. Barclay’s, Piper Jaffray, and Wedbush also initiated coverage of Pacira with optimistic outlooks.
Pacira’s sales pitch to hospitals and insurers will be far from easy, however. So Stack is turning his attention to assembling a new set of studies designed to convince healthcare payers that the Pacira product will save them money over the long run. “We’ve written a number of articles on what it cost to control pain in 2010, and a series of articles on opioid adverse events and what the cost of those would likely be,” he says.
Pacira is now teaming up with six large hospital chains to review patients’ charts—similar to what they did when they were launching bivalirudin at The Medicines Company. They plan to pinpoint exactly how inadequate pain control costs hospitals too much money. “We’re determining where post-surgical pain control with morphine leads to inappropriate resource utilization,” Stack says, which often occurs because patients suffer side effects that keep them in the hospital for days on end. “We’re setting the stage for what we’re going to compare ourselves to,” Stack says.
Stack says he’s in the process of rebuilding Pacira, and the company’s headcount has risen from 70 to 100 in advance of Exparel’s expected launch. The company brought in about $42 million in the IPO, roughly half what management was hoping to raise. The offering led the Wall Street Journal to include Pacira in a list inauspiciously titled “Biotech IPOs Continue Bleeding Money,” but Stack wasn’t fazed. “I’m still disappointed with the $7 offering price, but if you ask me if I’m sorry we went public, the answer would be a resounding ‘no,’” Stack says.
Pacira is planning other uses for the DepoFoam platform, including long-acting treatments for cancer and rheumatoid arthritis. Stack also points out that Pacira not only owns the worldwide rights to Exparel for human use, but it also owns the rights to develop it for the veterinary market, where bupivacaine is also the standard of care. Pursuing opportunities like those takes capital. Says Stack: “We have a lot of strategic opportunities to fund the company now that we would not have if we were private.”
Which part? Or do you really not have a point, except to denigrate (as expected)? If you think Stoll/Varney have proven worthy (by shareholders) over the course of their long, failing reign, that too is just cuckoo.
Come to think of it, his actual deals have boded well for shareholders, compared to Stoll (omitting the timing, and length of time, to close) . The amounts, no, but the terms and types of deals, yes. The problem is that nobody knows Varney. Stoll f*k'd this stock up so much, Varney can't get out of his pitch black, massive shadow. Corx & Varney are under the radar, which is a good thing, when it comes to boneheaded remarks, like predicting the signing of a deal in 6 weeks; and boneheaded decisions, like giving yourself a bonus for slaughtering the shareprice and selling the meat well below cost (that hugely positive deal--except for the share price--signed with Biovail)...
Given everything, he should now deal with the reality that it is time to go, along with Stoll, and the effortless BOD to boot. It will take real money to do it--a pharma will skin us and use our derma to blanket the executives and board. I hate to suggest it, but real snakes like R&R, JMP, Renaissance etc. are our best bet...
Relinquish control, leave with dignity, and pray for Cortex. Amen
I agree with your questions and concerns. First and foremost, they are out for their own survival. There is nothing great for shareholders in this approach, when they fail as often as they do. Too much cheerleading/sugarcoating (exaggeratedly positive reactions to salary-swallowing funding) only [falsely] validates their strategy, and encourages their lackluster resolve. One step forward and two steps back.
It is mildly pleasing that their is wiggle room, but I will continue to expect the same poor performance, which we have come to expect, from poor leadership. The wildcard is the already planted seeds--Servier, MJFF, even UAlberta+RD--which I hope propels us to a higher valuation. The lack of effort on AD is a complete tragedy--something, anything, should be happening on that front at any given time, just to have a horse in this revolutionary race for treatment options. I would consider this mgmt's biggest failure.
This would be a good time for mgmt to act selflessly and throw in the towel, and have the BOD throw out the poison pill. Look for new leadership, or just find a savvy M&A guy/firm who can be aligned with shareholders. Too much to ask? Of course, but it never hurts to ask anyway...
It's not really that difficult to admit failure, Lebron James mentioned his over and over again in the Press Conf., after Dirk and the Mav's showed them up to win the finals. I guess it takes integrity, something this mgmt team doesn't seem to have. It's 'yin and yang' guys, not 'ying' or 'yang'.
"Best of Day" posts (but not necessarily in order):
1) MF4:
Cortex Enters into New Agreement with Servier
— CORTEX TO RECEIVE UP TO $3 MILLION IF SERVIER OPTION IS EXERCISED —
Press Release Source: Cortex Pharmaceuticals, Inc. On Monday June 13, 2011, 7:31 am
IRVINE, Calif.--(BUSINESS WIRE)-- Cortex Pharmaceuticals, Inc. (OTCBB:CORX.ob - News) entered into a new agreement with Servier to sell its remaining rights to the jointly discovered high impact AMPAKINE® compound, CX1632 (S47445). Servier, France’s largest privately held pharmaceutical company, has provided an immediate, non-refundable payment of $1,000,000 to Cortex for the option to expand its rights. If Servier exercises the option to acquire sole ownership of the patent rights to CX1632 prior to October 31, 2011, it will pay Cortex an additional $2,000,000, as well as certain royalties and milestone payments to the University of California.
During the option period, Cortex and Servier remain joint owners of the patents and patent applications relating to CX1632.Cortex currently has rights to develop and market CX1632 in all of North America and selected South American countries as well as Australia and New Zealand.
On or before October 31, 2011, Servier may exercise its option to acquire sole ownership of the global patent rights to CX1632, along with a sub-license of Cortex's rights to all indications licensed from the University of California for use with CX1632. Cortex will not be entitled to any royalties or further payments from Servier’s development and commercialization of CX1632. Cortex retains all rights for the remaining AMPAKINE technology on a worldwide basis.
“We are delighted that Servier has chosen to continue to invest in the AMPAKINE program,” said Mark Varney, Ph.D., Cortex’s President and CEO. “The high-impact AMPAKINE technology, which includes CX1632, may represent a disease-modifying approach to treating memory and cognitive impairments in patients with Alzheimer’s disease and other disorders, given the demonstrated ability of the compounds to stimulate protective growth factors within the brain. Cortex is continuing to investigate both its low-impact and high-impact AMPAKINE compounds for indications in the psychiatric and neurological space.”
“We are very pleased to enter into such a new agreement with Cortex. We are committed to find innovative treatments for patients suffering from Alzheimer’s disease, and AMPA modulation is a promising way to improve cognitive disorders in such patients,” said Emmanuel Canet, MD, Head of Servier R&D.
About Servier
Servier is the leading independent French pharmaceutical company, established in 1954 by its founder, Jacques Servier, M.D., Pharm.D. The group is established in 140 countries and 88% of Servier products are prescribed outside of France. Sales turnover in 2010 reached 3.7 billion euros. More than 25% of Servier's turnover is invested in Research and Development. Servier therapeutic research fields are cardiovascular diseases, diabetes, neuropsychiatric disorders, cancer, and osteoarticular diseases. More information is available at: http://www.servier.com/
Cortex Pharmaceuticals, Inc.
Cortex, located in Irvine, California, is a neuroscience company focused on novel drug therapies for treating psychiatric disorders, neurological diseases and sleep apnea. Cortex is pioneering a class of proprietary pharmaceuticals called AMPAKINE compounds, which act to increase the strength of signals at connections between brain cells. The loss of these connections is thought to be responsible for memory and behavior problems in Alzheimer’s disease. Many psychiatric diseases, including schizophrenia, occur as a result of imbalances in the brain’s neurotransmitter system. These imbalances may be improved by using the AMPAKINE technology. Additionally, recent studies have shown that the AMPAKINE compounds also impact areas in the brain stem that control breathing. Recent work has focused on the potential treatment of sleep apnea disorders which can have a deleterious impact on numerous disease states including congestive heart failure. Also, respiratory depression caused by opioid analgesics, anesthetic agents and benzodiazepines can be reduced by AMPAKINE compounds. For additional information regarding Cortex, please visit the Company’s website at http://www.cortexpharm.com
Right. At least that was what Stoll told us. The negotiations were supposedly in progress when the FDA put a stop on the drug. I wonder too, was Stoll playing hardball (likely, because the stock was riding high at the time); were his hands full (probably so, with all the buzz); was he dreaming about the boatload of money he was about to retire on (no doubt)?
If he did get the deal signed before the hold, it could have changed everything. With a big player involved, they might have assisted with the costs associated with the animal study redo's, EM, etc. They may also have been able to exert some influence with the FDA on their ultimate decision regarding ADHD. But that's neither here nor there-- Stoll couldn't have envisioned how things were about to turn--we can't fault Stoll for the unfortunate timing (at least not without more info).
I do wonder, however, if Stoll adhered to acceptable/ethical business practices by not digging into the histo finding when it turned up in the animal (monkey?) data. That, as it happened, turned out to be the critical error which has stranded us in the desert. Is that water out there? Nope, that's a mirage (more dilution ahead).
Does anybody think that if there was a large shareholder(s) with a controlling interest in this company, these 'managers' would still be here? Maybe they should step away from their prolonged 'self-preservation' mode, and look at the situation from another, more objective/honest, perspective.
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