�Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics caller, announced that new presymptomatic data from its hypercholesterolemia program was published in Proceedings of the National Academy of Sciences (Frank-Kamenetsky, M., et al (August 11, 2008) Proc. Natl Acad. Sci. USA, 10.1073/pnas.0805434105). The promulgated, peer-reviewed information demonstrate for the offset time that a chemically synthesized minuscule interfering RNA (or siRNA, the molecules that mediate RNAi) targeting the factor proprotein convertase subtilisin/kexin type 9 (PCSK9) achieves acute and undestroyable lowering of total cholesterol levels in both mice and rats, and LDL cholesterol levels in nonhuman primates. Human genetic studies have correlative increased levels of PCSK9 with an increased risk of cardiovascular disease (Abifadel et al., Nature Genetics, 34 (2): 154-6; 2003). Conversely, human genetic studies have confirmed a most 88 per centum reduced risk of exposure of cardiac events in subjects with decreased levels of PCSK9 (Cohen et al., New England Journal of Medicine, 354: 1264-72; 2006).
The new inquiry, conducted by Alnylam scientists in coaction with scientists at UT Southwestern Medical Center in Dallas, Alnylam Europe (straightaway Roche Kulmbach), and the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, demonstrated in vivo efficaciousness for an RNAi sanative targeting PCSK9 in mice, rats, and non-human order Primates.
Specifically, the data showed:
- potent silencing of PCSK9 mRNA in mouse, rat, nonhuman primate, and in a transgenic model expressing human PCSK9;
- highly selective silencing of the PCSK9 messenger RNA (mRNA) by PCSK9 specific siRNAs as compared with unrelated siRNA controls and want of induction of INF? and TNF? by chemically modified siRNA compounds;
- proof of an RNAi mechanism of action as driven by 5'-RACE measurements;
- acute onset of action and long durability of biologic effect with reductions in total cholesterin levels in rodents and LDL cholesterin in order Primates observed by 48 to 72 hours that lasted 2 to 3 weeks after a single judicature;
- mechanistic rationale for cholesterin lowering as demonstrated by reduction in PCSK9 plasma protein levels and a concomitant addition in LDL-receptor levels in liver;
- therapeutic efficacy as measured by significant reductions in LDL-cholesterol levels by up to 60 pct of pre-dose levels in nonhuman primates; and,
- tolerability as analyzed by legion measurements including liver triglyceride levels with no statistical differences discovered between handling versus control groups.
Partial results of this study were antecedently presented at the XVI International Symposium on Drugs Affecting Lipid Metabolism in October 2007.
"We are very bucked up by the significance of these findings, including information in nonhuman primates, which continue to validate PCSK9 as an attractive aim for a systemic RNAi therapeutic approach given its ability to achieve acute and indestructible reductions in LDL cholesterin," said Victor Kotelianski, M.D., Ph.D., Vice President of Research at Alnylam. "PCSK9 is well validated based on human genetics, simply it has been a difficult protein to objective using traditional drug discovery modalities, such as small molecules and monoclonal antibodies. Thus, RNAi affords mayhap the only viable approaching for new medicines targeting this key mechanism for control of LDL metamorphosis."
"There is a clear unmet medical need for novel agents that john lower LDL cholesterol, and PCSK9 appears to be an fantabulous, genetically validated target for disease intervention," said Jay Horton, M.D., Professor of Internal Medicine and Molecular Genetics, UT Southwestern Medical Center. "Based on its novel mechanism of activeness and presymptomatic data to date, an RNAi remedial targeting PCSK9 has the potential to rapidly lour LDL cholesterin, while mayhap functioning synergistically with statins in the treatment of hypercholesterolemia."
Alnylam is developing ALN-PCS, an RNAi therapeutical targeting PCSK9, for the treatment of hypercholesterolemia; ALN-PCS is a systemically delivered RNAi therapeutical comprised of an optimized siRNA encapsulated in a liposomal nanoparticle formulation.
About PCSK9
PCSK9 is an important cistron involved in the metamorphosis of LDL cholesterol. The normal part of the PCSK9 protein is to break down the cellular phone surface receptor for LDL; when thither is less PCSK9 protein, there is more sensory receptor on the cell surface to remove LDL cholesterol from the bloodstream. In human studies, mutant forms of PCSK9 that take increased activity are linked with a familial form of hypercholesterolemia. Conversely, recent research published in the New England Journal of Medicine (Cohen et al., New England Journal of Medicine, 354: 1264-72; 2006) has demonstrated that former mutations in humans, including those that lower PCSK9 function, ar associated with decreased LDL cholesterol levels and an 88 percentage risk diminution in cardiovascular disease.
About RNA Interference (RNAi)
RNAi (RNA encumbrance) is a revolution in biology, representing a breakthrough in sympathy how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens one time every decennium or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug find today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biologic process of RNAi occurring in our cells, the creation of a major new course of instruction of medicines, known as RNAi therapeutics, is on the purview. RNAi therapeutics target the cause of diseases by potently silencing specific courier RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its curative expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the stream major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most ripe program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide kitchen stove of disease areas, including liver cancers, hypercholesterolemia, and Huntington's disease. The company's leadership position in rudimentary patents, applied science, and know-how relating to RNAi has enabled it to signifier major alliances with preeminent companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, and Kyowa Hakko Kogyo. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established "RNAi 2010" which includes the s be after to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to mannikin four or more new major line collaborations, all by the end of 2010. Alnylam is a joint proprietor of Regulus Therapeutics LLC, a joint venture focused on the discovery, growing, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit http://www.alnylam.com.
Alnylam Forward-Looking Statements
Various statements in this sack concerning Alnylam's future expectations, plans and prospects, appoint forward-looking statements for the purposes of the safe harbor commissariat under The Private Securities Litigation Reform Act of 1995. Actual results whitethorn differ materially from those indicated by these modern statements as a consequence of versatile important factors, including risks related to: Alnylam's approach to discover and acquire novel drugs, including ALN-PCS, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property; Alnylam's ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third base parties; Alnylam's ability to obtain additional funding to support its business activities; Alnylam's ability to understand future milestones and royalties as well as co-development and co-commercialization opportunities; Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory favourable reception for products; competition from others using technology like to Alnylam's and others developing products for similar uses; Alnylam's dependence on collaborators; and Alnylam's unforesightful operating history; as well as those risks more fully discussed in the "Risk Factors" section of its to the highest degree recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In gain, any advanced statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does non assume any obligation to update any forward-looking statements.
Alnylam Pharmaceuticals
More information
Saturday 16 August 2008
Thursday 7 August 2008
Eli Roth Is a �Bastard�
Inglorious Roth: Hostel managing director and Quentin Tarantino BFF Eli Roth will play a baseball-bat-swinging Nazi hunter in Inglorious Bastards. We wouldn't have anticipated this at all, but it totally works. [Variety]
Thurgood Marshall Doing Some Investigative Work: Laurence Fishburne is in talks to replace William Petersen as the star of CBS' linchpin crime drama CSI: Crime Scene Investigation. He's apparently being "heavily courted" to play the new lead, a doctor-scientist who has the same genetic profile as a serial killer but has never acted on the murderous impulse. At least Morpheus's monotone explanations of boring shit will be put to good use. [HR]
Bana Unleashes the Beast Within: Sometimes Hollywood knows you're having a rough morning and decides to cheer you up with something so dumb you can't help but love being alive. For example, Hollywood will say, "Check it out � Eric Bana is making Love the Beast, a documentary about his 25-year love affair with a 1974 Ford Falcon Coupe. That's right, it's nothing but Eric Bana getting sexy with his car, and also Dr. Phil is in part of it." Seriously, Hollywood? You're awesome at making us feel better. [Variety]
Grisham Gets Shanked: Phoenix Pictures has tapped Hairspray's Adam Shankman to direct Playing for Pizza, an adaptation of John Grisham's bestseller about an NFL quarterback who ends up playing semi-pro ball in Italy after blowing a shot at the Super Bowl. "We want to make this grittier than the book," says Shankman, crushing our hopes of finally seeing a football musical. [Variety]
Bayer Neck Deep in Fiasco: Music-video director Sam Bayer ("Smells Like Teen Spirit" (!!!)) will direct the action thriller Fiasco Heights for Universal. Story follows a gunman who teams up with a degenerate gambler to find a femme-fatale and a briefcase. Sound like a boring neo-noir mystery? Think again: Producer Michael Bay's involvement tacitly ensures ample explosions. [HR]
More info
Monday 30 June 2008
Tuesday 24 June 2008
Zombies testing new songs on the road
Kicking off North American tour in July
DETROIT -- The Zombies will have some new music to play for audience this summer -- even if it's not likely to be released until 2009.
Keyboardist Rod Argent said that the resurrected British group, which kicks off a 21-show North American tour on July 3 at the Comerica Tastefest in Detroit, has inserted two fresh songs into the show: his own "I Do Believe" and another, "Any Other Way," written by singer Colin Blunstone. "They go down just as well as anything in the set," Argent reports.
And he said more new material may surface in the near future for the group's followup to 2004's "As Far as I Can See ...."
"What I want to do is play each piece of new material on stage before we record it this time to make sure they work and really break them in on stage as much as possible," Argent explains. "I would also like to record the next album in a very organic way, without lots of overdubs -- just the guys really playing an arrangement that works well on stage and use that very much as the basis of the arrangement that we record."
Argent said the Zombies' "very intense" road schedule is going to make it hard to get the band in the studio for concentrated recording sessions; in that regard he predicts that "it's gonna be a year before a new album's out."
There will be Zombies product this year, though. The group's 40th anniversary performance of the "Odessey & Oracle" album during March at the Shepherd's Bush Empire Theatre in London was recorded for a CD and DVD, titled "The Zombies 'Odessey & Oracle' Revisited: The 40th Anniversary Concert." The CD is due out July 1, with the DVD coming later in the summer.
Argent said he and Blunstone will continue to celebrate the album's anniversary during the Zombies' summer tour, playing at least five songs from it. Meanwhile, the two other surviving founding members -- bassist Chris White and drummer Hugh Grundy, who both took part in the March shows, may factor into the Zombies' future, too.
"Getting back together with those guys was lovely," Argent notes, "and we may do a few selected concerts, one-off concerts, with them. But they don't want to be touring all the time, so I think everyone's happy with the situation as it is."
DETROIT -- The Zombies will have some new music to play for audience this summer -- even if it's not likely to be released until 2009.
Keyboardist Rod Argent said that the resurrected British group, which kicks off a 21-show North American tour on July 3 at the Comerica Tastefest in Detroit, has inserted two fresh songs into the show: his own "I Do Believe" and another, "Any Other Way," written by singer Colin Blunstone. "They go down just as well as anything in the set," Argent reports.
And he said more new material may surface in the near future for the group's followup to 2004's "As Far as I Can See ...."
"What I want to do is play each piece of new material on stage before we record it this time to make sure they work and really break them in on stage as much as possible," Argent explains. "I would also like to record the next album in a very organic way, without lots of overdubs -- just the guys really playing an arrangement that works well on stage and use that very much as the basis of the arrangement that we record."
Argent said the Zombies' "very intense" road schedule is going to make it hard to get the band in the studio for concentrated recording sessions; in that regard he predicts that "it's gonna be a year before a new album's out."
There will be Zombies product this year, though. The group's 40th anniversary performance of the "Odessey & Oracle" album during March at the Shepherd's Bush Empire Theatre in London was recorded for a CD and DVD, titled "The Zombies 'Odessey & Oracle' Revisited: The 40th Anniversary Concert." The CD is due out July 1, with the DVD coming later in the summer.
Argent said he and Blunstone will continue to celebrate the album's anniversary during the Zombies' summer tour, playing at least five songs from it. Meanwhile, the two other surviving founding members -- bassist Chris White and drummer Hugh Grundy, who both took part in the March shows, may factor into the Zombies' future, too.
"Getting back together with those guys was lovely," Argent notes, "and we may do a few selected concerts, one-off concerts, with them. But they don't want to be touring all the time, so I think everyone's happy with the situation as it is."
Monday 23 June 2008
Toby Keith's Cancer Charity Cashes In
Toby Keith has rocked the world of more than a few kids.
A two-day fundraiser presided over by the country music star raised $709,000 for Ally's House, a charity named after the late...
Sunday 22 June 2008
Spears' return to LA begins with scuffle at airport
LOS ANGELES - Britney Spears is back in Los Angeles, and it didn't take long for trouble to find her.
Within moments of arriving at Los Angeles International Airport on Friday evening, Spears' entourage was involved in a scuffle with a paparazzo.
Airport police say between 30 and 35 photographers swarmed her vehicle outside the terminal before a bodyguard pushed a camera into a photographer's face.
They say the paparazzo complained that the shove left a slight mark on the cheek, but cooler heads prevailed and no charges were filed.
The 26-year-old pop star was unscathed, and police say she was able to leave the airport safely.
See Also
Underwood pulls out of Dancing on Ice
'GMTV' presenter Michael Underwood has been forced to pull out of 'Dancing on Ice' after breaking his ankle.
The television presenter was learning his new routine for the next live show when he fell awkwardly on his ankle.
According to the show's official website, Underwood was rushed to hospital by ambulance, with X-rays later showing that he had suffered a break.
Speaking on 'GMTV' he said: "I'd like to say that I was attempting some amazing triple axel or something, but I was just trying to stop."
A 'Dancing on Ice' spokesperson said: "After breaking his ankle last night, Michael Underwood can no longer compete in 'Dancing on Ice'."
"The whole team are sad to see Michael leave the competition in this way and wish him a speedy recovery."
The television presenter was learning his new routine for the next live show when he fell awkwardly on his ankle.
According to the show's official website, Underwood was rushed to hospital by ambulance, with X-rays later showing that he had suffered a break.
Speaking on 'GMTV' he said: "I'd like to say that I was attempting some amazing triple axel or something, but I was just trying to stop."
A 'Dancing on Ice' spokesperson said: "After breaking his ankle last night, Michael Underwood can no longer compete in 'Dancing on Ice'."
"The whole team are sad to see Michael leave the competition in this way and wish him a speedy recovery."
DEVOTCHKAS
Artist: DEVOTCHKAS
Genre(s):
Rock: Punk-Rock
Discography:
Live Fast... Die Young
Year: 2001
Tracks: 14
![[1998] - Oi Toy EP](http://img.mp3fiesta.com/covers/18/18127/alb_73241_th.jpg)
[1998] - Oi Toy EP
Year: 1998
Tracks: 4
Pulser
Artist: Pulser
Genre(s):
Trance
Discography:
Point of Impact Incl Fractal Structure Remix Vinyl
Year: 2005
Tracks: 2
Wire
Dewi
Artist: Dewi
Genre(s):
Other
Discography:
Know Me
Year: 2003
Tracks: 12
Will Ferrell Puts the Funk in the Dunk
Jackson Scraps Plans For European Tour
JANET JACKSON has reportedly scrapped any plans to hit Europe with her forthcoming ROCK WITCHU tour following her record label's decision to cease promoting her latest album, DISCIPLINE.
The Nasty singer was due to play a series of live dates across Europe after embarking on her first series of concert shows for seven years in the U.S. and Canada, with her first gig in Vancouver, Canada on 10 September (08).
However, the singer has now decided to just dedicate herself to the North American leg of her tour, citing frustration with her Def Jam label bosses' lack of support in promoting her new album, according to People.com.
The star tells hip-hop website SOHH.com, "It was definitely in my heart to go to Europe and to support this album... it's about teamwork, it's not something I can totally do on my own.
"Unfortunately, things have turned out the way that they have with the differences between the label and myself."
Earlier this month (Jun08), Jackson told how there will be no further singles from her Discipline album, after record label bosses were disappointed with sales - shifting only 392,000 copies in the U.S.
She explained, "I'm trying to figure out a way to say this, but just to say it and to be quite honest, they just stopped all promotion whatsoever on the album, so I don't think you're going to hear another single off this album."
At the height of her popularity, Jackson scored 19 hit singles from just three LPs - Control, Rhythm Nation: 1812 and janet. And she still holds the record for scoring number ones in America from the same album, over three successive years.
The Nasty singer was due to play a series of live dates across Europe after embarking on her first series of concert shows for seven years in the U.S. and Canada, with her first gig in Vancouver, Canada on 10 September (08).
However, the singer has now decided to just dedicate herself to the North American leg of her tour, citing frustration with her Def Jam label bosses' lack of support in promoting her new album, according to People.com.
The star tells hip-hop website SOHH.com, "It was definitely in my heart to go to Europe and to support this album... it's about teamwork, it's not something I can totally do on my own.
"Unfortunately, things have turned out the way that they have with the differences between the label and myself."
Earlier this month (Jun08), Jackson told how there will be no further singles from her Discipline album, after record label bosses were disappointed with sales - shifting only 392,000 copies in the U.S.
She explained, "I'm trying to figure out a way to say this, but just to say it and to be quite honest, they just stopped all promotion whatsoever on the album, so I don't think you're going to hear another single off this album."
At the height of her popularity, Jackson scored 19 hit singles from just three LPs - Control, Rhythm Nation: 1812 and janet. And she still holds the record for scoring number ones in America from the same album, over three successive years.
M Ward
Artist: M Ward
Genre(s):
Indie
Rock
Discography:
Post War
Year: 2006
Tracks: 12
Transistor Radio
Year: 2005
Tracks: 16
Duet for Guitars #2
Year: 2004
Tracks: 16
Transfiguration of Vincent
Year: 2003
Tracks: 15
End of Amnesia
Year: 2002
Tracks: 14
Live Music and The Voice Of Strangers
Year: 2001
Tracks: 12
OK! Exclusive: Mario Lopez Opens Up About Break-Up
Michael Jackson in talks to become resident Las Vegas performer
LOS ANGELES - Michael Jackson may relaunch his career as a Las Vegas act, thanks to the private equity group that recently bought the loan on his Neverland Ranch in California to help the pop star avert foreclosure.The investment firm Colony Capital is discussing with Jackson various repayment options for the $23 million debt, including a possible long-term engagement as the resident performer of a Vegas casino or nightclub, a source familiar with the talks said.Colony Capital, based in Los Angeles, owns the Las Vegas Hilton and is a major shareholder in the Station Casinos chain.The source emphasized that no deal was in place and that a gig for Jackson in Las Vegas, a city of second chances for many faded superstars, was merely one idea under consideration as Colony Capital explores loan repayment scenarios with him.The talks with Jackson were first reported by the Wall Street Journal, which quoted Colony Capital CEO Tom Barrack as saying, "we've been having discussions with Mr. Jackson about a recapitalization and refinancing of Neverland in addition to various other business opportunities and mutual interests."
A Colony Capital spokesman told Reuters the company was not commenting further on the matter. Jackson's personal spokeswoman was not immediately available for comment.Bringing Jackson to Sin City as a performer would mark the biggest step the 49-year-old performer has taken toward a comeback since a child molestation trial left his career, his reputation and financial status in tatters three years ago.LAST COMEBACK PANNEDJackson became a virtual recluse after a California jury acquitted him of all charges in June 2005, moving his place of residence alternately to Ireland, Dubai and Bahrain. He reportedly is now living with his three young children in Pahrump, Nevada, about 60 miles from Las Vegas.A fleeting "comeback" appearance at a London awards show in 2006 was roundly panned by critics, though a 25th anniversary reissue of his blockbuster "Thriller" album earlier this year posted strong sales.Still, the mercurial performer known for extravagant spending has by all accounts remained mired in debt.In a bid to stave off insolvency in 2006, Jackson reached a deal to refinance more than $200 million in loans secured by his prized stake in the Beatles' song catalog.Those loans held by the New York private equity firm and hedge fund Fortress Investment Group, which in May sold Jackson's note on the Neverland Ranch to Colony Capital in a deal that averted foreclosure proceedings on the property.According to the Journal, Colony is negotiating an arrangement allowing Jackson to delay making payments for the time being in exchange for more money further down the road.Colony also is urging the singer to sell off Neverland as quickly as possible and to emerge from seclusion in Nevada to launch a career comeback in Vegas, the Journal said.One idea under discussion, the newspaper reported, was for Colony to install Jackson as a regular performer at one of its hotel-casinos, playing 180 nights a year. Another would be to create a musical extravaganza in which Jackson would appear 20 or 30 times a year, possibly with his brothers.Colony also is pressing Jackson to go on TV, perhaps on Oprah Winfrey's show, to make a public statement putting the Neverland Ranch and the controversy connected with it behind him, and to perform in a TV special proving to the world that he can still sing and dance.- REUTERS/Nielsen
A Colony Capital spokesman told Reuters the company was not commenting further on the matter. Jackson's personal spokeswoman was not immediately available for comment.Bringing Jackson to Sin City as a performer would mark the biggest step the 49-year-old performer has taken toward a comeback since a child molestation trial left his career, his reputation and financial status in tatters three years ago.LAST COMEBACK PANNEDJackson became a virtual recluse after a California jury acquitted him of all charges in June 2005, moving his place of residence alternately to Ireland, Dubai and Bahrain. He reportedly is now living with his three young children in Pahrump, Nevada, about 60 miles from Las Vegas.A fleeting "comeback" appearance at a London awards show in 2006 was roundly panned by critics, though a 25th anniversary reissue of his blockbuster "Thriller" album earlier this year posted strong sales.Still, the mercurial performer known for extravagant spending has by all accounts remained mired in debt.In a bid to stave off insolvency in 2006, Jackson reached a deal to refinance more than $200 million in loans secured by his prized stake in the Beatles' song catalog.Those loans held by the New York private equity firm and hedge fund Fortress Investment Group, which in May sold Jackson's note on the Neverland Ranch to Colony Capital in a deal that averted foreclosure proceedings on the property.According to the Journal, Colony is negotiating an arrangement allowing Jackson to delay making payments for the time being in exchange for more money further down the road.Colony also is urging the singer to sell off Neverland as quickly as possible and to emerge from seclusion in Nevada to launch a career comeback in Vegas, the Journal said.One idea under discussion, the newspaper reported, was for Colony to install Jackson as a regular performer at one of its hotel-casinos, playing 180 nights a year. Another would be to create a musical extravaganza in which Jackson would appear 20 or 30 times a year, possibly with his brothers.Colony also is pressing Jackson to go on TV, perhaps on Oprah Winfrey's show, to make a public statement putting the Neverland Ranch and the controversy connected with it behind him, and to perform in a TV special proving to the world that he can still sing and dance.- REUTERS/Nielsen
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