Alnylam Pharmaceuticals Inc (ALNY)

[bigstocksnbonds]

Congrats on your plunge today great price you got! Way to go! Great job on the options too! : )

[jrf30]

The options expired with full 100% profit.

Today I took the plunge. PIcked up 400 shares. At a LOT lower price than it was when we were looking at it before. Also may sell some calls soon (NOt yet) and thinking of selling a few more out of the money puts. PIck up on that spread too.

But took a small plunge today on the stock ...

[jrf30]

Finally! Down to $84 now. Down from $109 a week ago. What a drop!!

I am going to make a move on this drop. Don't want to catch a falling knife, but selling puts or buying stock and writing out of the money calls to give a little income even if it goes down, makes sense finally.

I hoped (And sorta called it here) this when it was at $124. NOw I'm ready. ANyone else think it is worth finally buying?

[jrf30]

Last Friday it was at $109 3/4. Down from the $140 high, but still not low enough. today, six days later, it is at $88 3/4, and still falling. Down 20% in a week!

That's more like it.

[DewDiligence]

MDCO/ALNY—RNAi-based cholesterol drug shows durability:

#msg-116612954

[bigstocksnbonds]

Great way to buy it while limiting your risk YES!! Great smart move hope you make a bundle off it!! : )

[jrf30]

Took the plunge. Sold some Sept 18th $90 puts this morning, while it was down. Thought of lowering to the $85s, but if for some reason it is still down by September I can roll them. Got more for the $90s.

Now I either own it at about $84, if it gets put to me, or I make $6 plus per share on the stock, with nothing invested in it. A way to make money off this with some limitations on my risk, as opposed to buying it at $94 today, which is where it is (was).

[bigstocksnbonds]

Selling some puts on this one may be the way to go, smart move! Good thinking there!! Enjoy success!! : )

[jrf30]

I'm thinking of selling some puts on this one. Sell at September $90 put at $3.20, and you either buy it at $86.80 (Not a bad price. Much better than the $120 it was at recently) or you get to keep $3.20 per share and never own it. Not a bad deal either way.

Yes, I think I'll watch Monday's action and see if we can get another good drop. If so, I'll hold off. If not, I'll do the put and place a bet below the market that can pay me even if it goes down from $100 to $91.

[bigstocksnbonds]

Yes it is looking better! May buy soon! THANKS!! : )

[jrf30]

It broke through 100 todAy. I'm still not buying yet, but it's looking better..,

[bigstocksnbonds]

It might be a bargain lower priced!! Thanks!!

[jrf30]

It hit $140 last Tuesday. Now the market is coming down some, and as expected, so is this. Down to $115 today.

Still think we might see a big reversal in the market, so I'm thinking this goes a LOT lower.

Shoot, might even have to look at some puts on this, or a short position. Should have thought of that at $140! Dang.

[bigstocksnbonds]

Thank you much for your analysis on this stock! I too think if it pulls back under 100 it would be a good buy! Thanks will wait too!! Thank you lots!!

[jrf30]

I've done a lot of research over the last week on this. My conclusion (Hence opinion, after digesting the facts) is that it is not an urgent buy. the market in general is high, imo, and this has followed it up. I think we are due for a correction, and maybe a large one, and if that happens this stock will correct too. It is owned mostly by institutions, not retail buyers, so as they lose money and people pull out of the funds (Which is what owns this stock) I see them selling off.

I'm personally going to wait. See if we can see 15,000 on the dow and have this under $100. MIght miss it, but still will wait.

[bigstocksnbonds]

Would you advise taking a position here? Heard this technology is life changing both medically and financially!! Thanks for your reply!!

[Kinny]

Its largely followed/traded by institutions. Not many here are interested.

[jrf30]

The stock up SOO much in 2015, and not a single post since december??

Anyone here?

[Stock_Strategies]

ALNY strong reversal as usual.

[stocktrademan]

$ALNY DD Notes ~ http://www.ddnotesmaker.com/ALNY

bullish

$ALNY recent news/filings

## source: finance.yahoo.com

Tue, 25 Nov 2014 21:32:05 GMT ~ Alnylam to Webcast Presentations at Upcoming Investor Conferences

[at noodls] - 11.25.2014 CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced that management will present a company overview at the ...

read full: http://www.noodls.com/view/8CE2A707E7C2BEF0A5A8C4C01792EFE066605F98
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Tue, 25 Nov 2014 21:00:00 GMT ~ Alnylam to Webcast Presentations at Upcoming Investor Conferences

[Business Wire] - Alnylam Pharmaceuticals, Inc. , a leading RNAi therapeutics company, today announced that management will present a company overview at the 2014 Deutsche Bank BioFEST on Tuesday, December 2, 2014 at 2:15 p.m.

read full: http://finance.yahoo.com/news/alnylam-webcast-presentations-upcoming-investor-210000331.html
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Mon, 17 Nov 2014 22:40:02 GMT ~ Alnylam Reports Positive Initial Phase II Data on Revusiran


read full: http://finance.yahoo.com/news/alnylam-reports-positive-initial-phase-224002949.html
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Mon, 17 Nov 2014 22:08:29 GMT ~ Alnylam Presents New Pre-Clinical Data on RNAi Therapeutic Programs for Cardio-Metabolic Diseases at American Heart Association Scientific Sessions 2014

[at noodls] - 11.17.2014 - New Non-Human Primate Data on ALN-PCSsc Show Clamped Knockdown of PCSK9 up to 92% and LDL-C Reductions of up to 77% with Monthly Subcutaneous Dosing Regimen; Phase 1 Study with ALN-PCSsc on ...

read full: http://www.noodls.com/view/0745AD1E2D372039E11F2D981283CAF2F40C52F7
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Mon, 17 Nov 2014 22:00:00 GMT ~ Alnylam Presents New Pre-Clinical Data on RNAi Therapeutic Programs for Cardio-Metabolic Diseases at American Heart Association Scientific Sessions 2014

[Business Wire] - Alnylam Pharmaceuticals, Inc. , a leading RNAi therapeutics company, announced today that it has presented new pre-clinical data from its investigational RNAi therapeutic programs toward genetically validated targets in development for the treatment of cardiovascular metabolic diseases, including: ALN-PCSsc targeting PCSK9 for the treatment of hypercholesterolemia; ALN-AC3 targeting apolipoprotein ...

read full: http://finance.yahoo.com/news/alnylam-presents-pre-clinical-data-220000218.html
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$ALNY charts

basic chart ## source: stockcharts.com



basic chart ## source: stockscores.com



big daily chart ## source: stockcharts.com



big weekly chart ## source: stockcharts.com


$ALNY company information

## source: otcmarkets.com

Link: http://www.otcmarkets.com/stock/ALNY/company-info
Ticker: $ALNY
OTC Market Place: Not Available
CIK code: 0001178670
Company name: Alnylam Pharmaceuticals, Inc.
Company website: http://www.alnylam.com
Incorporated In: DE, USA


$ALNY share structure

## source: otcmarkets.com

Market Value: $7,735,421,100 a/o Nov 28, 2014
Shares Outstanding: 76,931,090 a/o Oct 31, 2014
Float: Not Available
Authorized Shares: Not Available
Par Value: 0.0001
$ALNY extra dd links

Company name: Alnylam Pharmaceuticals, Inc.
Company website: http://www.alnylam.com

## STOCK DETAILS ##
After Hours Quote (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/after-hours
Option Chain (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/option-chain
Historical Prices (yahoo.com): http://finance.yahoo.com/q/hp?s=ALNY+Historical+Prices
Company Profile (yahoo.com): http://finance.yahoo.com/q/pr?s=ALNY+Profile
Industry (yahoo.com): http://finance.yahoo.com/q/in?s=ALNY+Industry

## COMPANY NEWS ##
Market Stream (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/stream
Latest news (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/news - http://finance.yahoo.com/q/h?s=ALNY+Headlines

## STOCK ANALYSIS ##
Analyst Research (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/analyst-research
Guru Analysis (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/guru-analysis
Stock Report (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/stock-report
Competitors (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/competitors
Stock Consultant (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/stock-consultant
Stock Comparison (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/stock-comparison
Investopedia (investopedia.com): http://www.investopedia.com/markets/stocks/ALNY/?wa=0
Research Reports (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/research
Basic Tech. Analysis (yahoo.com): http://finance.yahoo.com/q/ta?s=ALNY+Basic+Tech.+Analysis
Barchart (barchart.com): http://www.barchart.com/quotes/stocks/ALNY
DTCC (dtcc.com): http://search2.dtcc.com/?q=Alnylam+Pharmaceuticals%2C+Inc.&x=10&y=8&sp_p=all&sp_f=ISO-8859-1
Spoke company information (spoke.com): http://www.spoke.com/search?utf8=%E2%9C%93&q=Alnylam+Pharmaceuticals%2C+Inc.
Corporation WIKI (corporationwiki.com): http://www.corporationwiki.com/search/results?term=Alnylam+Pharmaceuticals%2C+Inc.&x=0&y=0
WHOIS (domaintools.com): http://whois.domaintools.com/http://www.alnylam.com
Alexa (alexa.com): http://www.alexa.com/siteinfo/http://www.alnylam.com#
Corporate website internet archive (archive.org): http://web.archive.org/web/*/http://www.alnylam.com

## FUNDAMENTALS ##
Call Transcripts (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/call-transcripts
Annual Report (companyspotlight.com): http://www.companyspotlight.com/library/companies/keyword/ALNY
Income Statement (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/financials?query=income-statement
Revenue/EPS (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/revenue-eps
SEC Filings (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/sec-filings
Edgar filings (sec.gov): http://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=0001178670&owner=exclude&count=40
Latest filings (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/filings
Latest financials (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/financials
Short Interest (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/short-interest
Dividend History (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/dividend-history
RegSho (regsho.com): http://www.regsho.com/tools/symbol_stats.php?sym=ALNY&search=search
OTC Short Report (otcshortreport.com): http://otcshortreport.com/index.php?index=ALNY
Short Sales (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/short-sales
Key Statistics (yahoo.com): http://finance.yahoo.com/q/ks?s=ALNY+Key+Statistics
Insider Roster (yahoo.com): http://finance.yahoo.com/q/ir?s=ALNY+Insider+Roster
Income Statement (yahoo.com): http://finance.yahoo.com/q/is?s=ALNY
Balance Sheet (yahoo.com): http://finance.yahoo.com/q/bs?s=ALNY
Cash Flow (yahoo.com): http://finance.yahoo.com/q/cf?s=ALNY+Cash+Flow&annual

## HOLDINGS ##
Major holdings (cnbc.com): http://data.cnbc.com/quotes/ALNY/tab/8.1
Insider transactions (yahoo.com): http://finance.yahoo.com/q/it?s=ALNY+Insider+Transactions
Insider transactions (secform4.com): http://www.secform4.com/insider-trading/ALNY.htm
Insider transactions (insidercrow.com): http://www.insidercow.com/history/company.jsp?company=ALNY
Ownership Summary (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/ownership-summary
Institutional Holdings (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/institutional-holdings
Insiders (SEC Form 4) (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/insider-trades
Insider Disclosure (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/insider-transactions

## SOCIAL MEDIA AND OTHER VARIOUS SOURCES ##
PST (pennystocktweets.com): http://www.pennystocktweets.com/stocks/profile/ALNY
Market Watch (marketwatch.com): http://www.marketwatch.com/investing/stock/ALNY
Bloomberg (bloomberg.com): http://www.bloomberg.com/quote/ALNY:US
Morningstar (morningstar.com): http://quotes.morningstar.com/stock/s?t=ALNY
Bussinessweek (businessweek.com): http://investing.businessweek.com/research/stocks/snapshot/snapshot_article.asp?ticker=ALNY



$ALNY DD Notes ~ http://www.ddnotesmaker.com/ALNY

[stocktrademan]

$ALNY DD Notes ~ http://www.ddnotesmaker.com/ALNY

bullish
ascending triangle breakout

target 122 (1.3x gain cash, or 2x on margin)


$ALNY recent news/filings

## source: finance.yahoo.com

Tue, 21 Oct 2014 13:00:36 GMT ~ Alnylam (ALNY) Shares March Higher, Can It Continue?


read full: http://finance.yahoo.com/news/alnylam-alny-shares-march-higher-130036615.html
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Mon, 20 Oct 2014 12:12:44 GMT ~ Alnylam Launches Alnylam Assist™, Dedicated to Providing Support to Patients, Families, and Caregivers in Certain Genetic Diseases

[at noodls] - 10.20.2014 - Initiates Free Screening Support for Genetic Mutations Associated with Familial Amyloidotic Polyneuropathy (FAP) in Transthyretin-Mediated Amyloidosis (ATTR) as Initial Effort under Alnylam ...

read full: http://www.noodls.com/view/04E80C124CA876E8182CA9FCE25695784EA2CA46
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Mon, 20 Oct 2014 12:00:00 GMT ~ Alnylam Launches Alnylam Assist™, Dedicated to Providing Support to Patients, Families, and Caregivers in Certain Genetic Diseases

[Business Wire] - Alnylam Pharmaceuticals, Inc. , a leading RNAi therapeutics company, announced today that it has launched Alnylam Assist™, a program dedicated to providing support to patients, families, and caregivers.

read full: http://finance.yahoo.com/news/alnylam-launches-alnylam-assist-dedicated-120000565.html
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Thu, 16 Oct 2014 11:44:12 GMT ~ The Zacks Analyst Blog Highlights: Auxilium, Gilead, AbbVie, Amgen and Alnylam


read full: http://finance.yahoo.com/news/zacks-analyst-blog-highlights-auxilium-114412296.html
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Thu, 16 Oct 2014 11:25:00 GMT ~ Moving Average Crossover Alert: Alnylam Pharmaceuticals (ALNY)


read full: http://finance.yahoo.com/news/fitch-retains-capital-ones-ratings-163001256.html
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$ALNY charts

basic chart ## source: stockcharts.com



basic chart ## source: stockscores.com



big daily chart ## source: stockcharts.com



big weekly chart ## source: stockcharts.com


$ALNY company information

## source: otcmarkets.com

Link: http://www.otcmarkets.com/stock/ALNY/company-info
Ticker: $ALNY
OTC Market Place: Not Available
CIK code: 0001178670
Company name: Alnylam Pharmaceuticals, Inc.
Company website: http://www.alnylam.com
Incorporated In: DE, USA


$ALNY share structure

## source: otcmarkets.com

Market Value: $7,165,136,027 a/o Oct 24, 2014
Shares Outstanding: 76,354,817 a/o Jul 31, 2014
Float: Not Available
Authorized Shares: Not Available
Par Value: 0.0001
$ALNY extra dd links

Company name: Alnylam Pharmaceuticals, Inc.
Company website: http://www.alnylam.com

## STOCK DETAILS ##
After Hours Quote (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/after-hours
Option Chain (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/option-chain
Historical Prices (yahoo.com): http://finance.yahoo.com/q/hp?s=ALNY+Historical+Prices
Company Profile (yahoo.com): http://finance.yahoo.com/q/pr?s=ALNY+Profile
Industry (yahoo.com): http://finance.yahoo.com/q/in?s=ALNY+Industry

## COMPANY NEWS ##
Market Stream (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/stream
Latest news (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/news - http://finance.yahoo.com/q/h?s=ALNY+Headlines

## STOCK ANALYSIS ##
Analyst Research (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/analyst-research
Guru Analysis (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/guru-analysis
Stock Report (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/stock-report
Competitors (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/competitors
Stock Consultant (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/stock-consultant
Stock Comparison (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/stock-comparison
Investopedia (investopedia.com): http://www.investopedia.com/markets/stocks/ALNY/?wa=0
Research Reports (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/research
Basic Tech. Analysis (yahoo.com): http://finance.yahoo.com/q/ta?s=ALNY+Basic+Tech.+Analysis
Barchart (barchart.com): http://www.barchart.com/quotes/stocks/ALNY
DTCC (dtcc.com): http://search2.dtcc.com/?q=Alnylam+Pharmaceuticals%2C+Inc.&x=10&y=8&sp_p=all&sp_f=ISO-8859-1
Spoke company information (spoke.com): http://www.spoke.com/search?utf8=%E2%9C%93&q=Alnylam+Pharmaceuticals%2C+Inc.
Corporation WIKI (corporationwiki.com): http://www.corporationwiki.com/search/results?term=Alnylam+Pharmaceuticals%2C+Inc.&x=0&y=0
WHOIS (domaintools.com): http://whois.domaintools.com/http://www.alnylam.com
Alexa (alexa.com): http://www.alexa.com/siteinfo/http://www.alnylam.com#
Corporate website internet archive (archive.org): http://web.archive.org/web/*/http://www.alnylam.com

## FUNDAMENTALS ##
Call Transcripts (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/call-transcripts
Annual Report (companyspotlight.com): http://www.companyspotlight.com/library/companies/keyword/ALNY
Income Statement (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/financials?query=income-statement
Revenue/EPS (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/revenue-eps
SEC Filings (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/sec-filings
Edgar filings (sec.gov): http://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=0001178670&owner=exclude&count=40
Latest filings (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/filings
Latest financials (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/financials
Short Interest (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/short-interest
Dividend History (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/dividend-history
RegSho (regsho.com): http://www.regsho.com/tools/symbol_stats.php?sym=ALNY&search=search
OTC Short Report (otcshortreport.com): http://otcshortreport.com/index.php?index=ALNY
Short Sales (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/short-sales
Key Statistics (yahoo.com): http://finance.yahoo.com/q/ks?s=ALNY+Key+Statistics
Insider Roster (yahoo.com): http://finance.yahoo.com/q/ir?s=ALNY+Insider+Roster
Income Statement (yahoo.com): http://finance.yahoo.com/q/is?s=ALNY
Balance Sheet (yahoo.com): http://finance.yahoo.com/q/bs?s=ALNY
Cash Flow (yahoo.com): http://finance.yahoo.com/q/cf?s=ALNY+Cash+Flow&annual

## HOLDINGS ##
Major holdings (cnbc.com): http://data.cnbc.com/quotes/ALNY/tab/8.1
Insider transactions (yahoo.com): http://finance.yahoo.com/q/it?s=ALNY+Insider+Transactions
Insider transactions (secform4.com): http://www.secform4.com/insider-trading/ALNY.htm
Insider transactions (insidercrow.com): http://www.insidercow.com/history/company.jsp?company=ALNY
Ownership Summary (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/ownership-summary
Institutional Holdings (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/institutional-holdings
Insiders (SEC Form 4) (nasdaq.com): http://www.nasdaq.com/symbol/ALNY/insider-trades
Insider Disclosure (otcmarkets.com): http://www.otcmarkets.com/stock/ALNY/insider-transactions

## SOCIAL MEDIA AND OTHER VARIOUS SOURCES ##
PST (pennystocktweets.com): http://www.pennystocktweets.com/stocks/profile/ALNY
Market Watch (marketwatch.com): http://www.marketwatch.com/investing/stock/ALNY
Bloomberg (bloomberg.com): http://www.bloomberg.com/quote/ALNY:US
Morningstar (morningstar.com): http://quotes.morningstar.com/stock/s?t=ALNY
Bussinessweek (businessweek.com): http://investing.businessweek.com/research/stocks/snapshot/snapshot_article.asp?ticker=ALNY



$ALNY DD Notes ~ http://www.ddnotesmaker.com/ALNY

[BiotehPickList]

Good article for Alnylam (ALNY) "Alnylam Keeps Making New Strides In RNAi Research"

http://www.biotechpicklist.com/alnylam-keeps-making-new-strides-in-rnai-research/

[Wildbilly]

Alnylam Initiates EXPLORE, a Prospective Observational Study of Patients with Hepatic Porphyrias

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, and collaborators from the American Porphyria Consortium and The European Porphyria Network have initiated the EXPLORE trial, a prospective observational study of patients with hepatic porphyrias, including Acute Intermittent Porphyria (AIP), Variegate Porphyria, and Hereditary Coproporphyria, suffering from recurrent attacks. With this study, Alnylam and clinical investigators aim to learn more about the clinical course, management, and disease burden of patients with hepatic porphyrias that suffer from recurrent attacks. Alnylam is currently advancing ALN-AS1, a subcutaneously administered investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS-1) for the treatment of hepatic porphyrias, and expects to file an IND or IND equivalent in late 2014 or early 2015.

Read more: .http://www.businesswire.com/portal/site/biospace/index.jsp?ndmViewId=news_view&newsId=20141001005203&newsLang=en



.

[Wildbilly]

The Second Coming of RNAi | The Scientist Magazine®


http://www.the-scientist.com/?articles.view/articleNo/40871/title/The-Second-Coming-of-RNAi/

[Wildbilly]

New nanoparticles offer best-ever gene silencing,
could help treat liver diseases

Posted: Feb 11, 2014 3:46 P:M
(Nanowerk News) Inspired by tiny particles that carry cholesterol through the body, MIT chemical engineers have designed nanoparticles that can deliver snippets of genetic material that turn off disease-causing genes.
This approach, known as RNA interference (RNAi), holds great promise for treating cancer and other diseases. However, delivering enough RNA to treat the diseased tissue, while avoiding side effects in the rest of the body, has proven difficult.
The new MIT particles, which encase short strands of RNA within a sphere of fatty molecules and proteins, silence target genes in the liver more efficiently than any previous delivery system, the researchers found in a study of mice.
“What we’re excited about is how it only takes a very small amount of RNA to cause gene knockdown in the whole liver. The effect is specific to the liver — we get no effect in other tissues where you don’t want it,” says Daniel Anderson, the Samuel A. Goldblith Associate Professor of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research.
Anderson is senior author of a paper describing the particles in the Proceedings of the National Academy of Sciences ("Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates") the week of Feb. 10. Robert Langer, the David H. Koch Institute Professor at MIT, is also an author.

MIT engineers designed nanoparticles that can deliver short strands of RNA (green) into cells (nuclei are stained blue). (Image: Gaurav Sahay, Yizhou Dong, and Omid Veiseh)
The research team, which included scientists from Alnylam Pharmaceuticals, also found that the nanoparticles could powerfully silence genes in nonhuman primates. The technology has been licensed to a company for commercial development.
Natural inspiration
RNA interference is a naturally occurring phenomenon that scientists have been trying to exploit since its discovery in 1998. Snippets of RNA known as short interfering RNA (siRNA) turn off specific genes inside living cells by destroying the messenger RNA molecules that carry DNA’s instructions to the rest of the cell.
Scientists hope this approach could offer new treatments for diseases caused by single mutations, such as Huntington’s disease, or cancer, by blocking mutated genes that promote cancerous behavior. However, developing RNAi therapies has proven challenging because it is difficult to deliver large quantities of siRNA to the right location without causing side effects in other tissues or organs.
In previous studies, Anderson and Langer showed they could block multiple genes with small doses of siRNA by wrapping the RNA in fatlike molecules called lipidoids. In their latest work, the researchers set out to improve upon these particles, making them more efficient, more selective, and safer, says Yizhou Dong, a postdoc at the Koch Institute and lead author of the paper.
“We really wanted to develop materials for clinical use in the future,” he says. “That’s our ultimate goal for the material to achieve.”
The design inspiration for the new particles came from the natural world — specifically, small particles known as lipoproteins, which transport cholesterol and other fatty molecules throughout the body.
Like lipoprotein nanoparticles, the MIT team’s new lipopeptide particles are spheres whose outer membranes are composed of long chains with a fatty lipid tail that faces into the particle. In the new particles, the head of the chain, which faces outward, is an amino acid (the building blocks of proteins). Strands of siRNA are carried inside the sphere, surrounded by more lipopeptide molecules. Molecules of cholesterol embedded in the membrane and an outer coating of the polymer PEG help to stabilize the structure.
The researchers tuned the particles’ chemical properties, which determine their behavior, by varying the amino acids included in the particles. There are 21 amino acids found in multicellular organisms; the researchers created about 60 lipopeptide particles, each containing a different amino acid linked with one of three chemical groups — an acrylate, an aldehyde, or an epoxide. These groups also contribute to the particles’ behavior.
David Putnam, an associate professor of biomedical engineering at Cornell University, says he is impressed with the team’s approach to mimicking how the body transports fatty molecules with lipoprotein particles.
“They hijacked that machinery and made something that looks like the lipoprotein structures and will carry siRNA straight to the liver. They’re building on Mother Nature and making it as efficient as possible,” says Putnam, who was not part of the research team.
Targeted strike
The researchers then tested the particles’ ability to shut off the gene for a blood clotting protein called Factor VII, which is produced in the liver by cells called hepatocytes. Measuring Factor VII levels in the bloodstream reveals how effective the siRNA silencing is.
In that initial screen, the most efficient particle contained the amino acid lysine linked to an epoxide, so the researchers created an additional 43 nanoparticles similar to that one, for further testing. The best of these compounds, known as cKK-E12, achieved gene silencing five times more efficiently than that achieved with any previous siRNA delivery vehicle.
In a separate experiment, the researchers delivered siRNA to block a tumor suppressor gene that is expressed in all body tissues. They found that siRNA delivery was very specific to the liver, which should minimize the risk of off-target side effects.
“That’s important because we don’t want the material to silence all the targets in the human body,” Dong says. “If we want to treat patients with liver disease, we only want to silence targets in the liver, not other cell types.”
In tests in nonhuman primates, the researchers found that the particles could effectively silence a gene called TTR (transthyretin), which has been implicated in diseases including senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy.
The MIT team is now trying to learn more about how the particles behave and what happens to them once they are injected, in hopes of further improving the particles’ performance. They are also working on nanoparticles that target organs other than the liver, which is more challenging because the liver is a natural destination for foreign material filtered out of the blood.
Source: By Anne Trafton, MIT

http://www.nanowerk.com/nanotechnology_news/newsid=34347.php

[sharky]

RSI oversold here IMO




$ALNY

[One Flap]

Wow! Biotech investing can be so exhilarating!

[surf1944]

8:00AM Alnylam Pharma presents new pre-clinical data on pharmacology of GalNAc-siRNA Conjugates; new results demonstrate achievement of steady state liver drug levels during chronic dosing with no evidence for drug accumulation (ALNY) 63.00 :

Co announced today that it has presented new pre-clinical data on the pharmacology of GalNAc-siRNA conjugates at the 12th US-Japan Symposium on Drug Delivery Systems held December 16 -- 20, 2013 in Lahaina, Maui, Hawaii. In a presentation titled "Advances in Systemic Delivery of RNAi Therapeutics,"
Alnylam scientists presented new data on tissue drug levels and sustained target knockdown achieved with long-term chronic dosing of GalNAc-siRNA conjugates.
GalNAc-siRNA conjugates are a proprietary Alnylam delivery platform, and are designed to achieve targeted delivery of RNAi therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor. This targeted delivery platform enables subcutaneous dose administration with a wide therapeutic index, and has demonstrated potent and durable gene silencing, as well as a favorable tolerability profile, in clinical and pre-clinical studies from multiple programs in the company's "Alnylam 5x15" product pipeline.
The new data demonstrate the pharmacodynamic and pharmacokinetic properties of GalNAc-siRNA conjugates following repeat dosing. Specifically, in mouse studies, weekly subcutaneous dosing of ALN-AT3, an RNAi therapeutic targeting antithrombin (AT), resulted in mean steady state liver drug levels of approximately 0.4 and 1.1 micrograms per gram at doses of 0.2 and 0.5 mg/kg, respectively. These drug levels were shown to correspond to roughly 60% and 75% knockdown of serum AT, and compare very favorably with other oligonucleotide platforms requiring greater than 100 micrograms of drug per gram of tissue for similar biologic effects; this corresponds to 100- to 1000-fold lower levels of required tissue exposure for GalNAc-siRNA conjugates, which could underscore the potential for a more favorable tolerability profile.
Further, no evidence of drug accumulation in liver tissue during chronic dosing was observed after the third weekly dose. In addition, data from a long-term pharmacology study were presented with a GalNAc-siRNA conjugate targeting the transthyretin (TTR) mRNA in mice. Weekly dosing at 1.0 and 2.5 mg/kg led to steady TTR knockdown of 50% and 80%, respectively, which was sustained for the entire 196-day time period analyzed. The TTR knockdown effect was found to be highly consistent with very low levels of inter-animal variation. Finally, the steady level of knockdown was achieved with no evidence of tachyphylaxis or sensitization.

[surf1944]

8:07AM Alnylam Pharma initiates phase ii clinical trial with ALN-TTRsc; Pilot Phase II trial now open for enrollment for attr patients with familial amyloidotic cardiomyopathy or senile systemic amyloidosis (ALNY) 59.42 : Co announced that it has initiated a pilot Phase II study with ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting the transthyretin gene in development for the treatment of TTR-mediated amyloidosis (ATTR). The Phase II trial, which is now open for enrollment, is aimed at evaluating the tolerability and preliminary clinical activity of ALN-TTRsc in TTR cardiac amyloidosis patients with familial amyloidotic cardiomyopathy -- which is caused by autosomal dominant mutations in the TTR gene, or senile systemic amyloidosis (SSA) -- which is caused by idiopathic accumulation of wild-type TTR in the heart. The company expects to present data from the Phase II trial in late 2014, and assuming positive results, begin a Phase III trial in TTR cardiac amyloidosis patients by the end of 2014.

The Phase II trial is an open-label, multi-dose study of ALN-TTRsc, designed to enroll approximately 15 TTR cardiac amyloidosis patients with FAC or SSA. The primary objective of the study is to evaluate the general tolerability of ALN-TTRsc. Patients will receive 5 daily doses followed by 5 weekly doses of 5 mg/kg, with follow-up through Day 90; in the Phase I ALN-TTRsc study, this dose resulted in an up to 93% TTR knockdown and a mean nadir knockdown of approximately 88%, and was found to be generally safe and well tolerated. Secondary objectives include assessment of clinical activity as measured by knockdown of serum TTR levels and additional tests, such as cardiac imaging (including echocardiography and cardiac MRI), circulating cardiac biomarkers (NT-proBNP and troponins T and I), 6-minute walk test, New York Heart Association (NYHA) classification, and measures of heart failure symptoms and quality of life (Kansas City Cardiomyopathy Questionnaire and EQ-5D QOL). Patients completing the Phase II trial will be eligible to participate in an open-label extension (OLE) study for further assessment of general tolerability and clinical activity with long-term dosing; the ALN-TTRsc Phase II OLE study is expected to be initiated in mid-2014.

[pete7]

This is going to triple digits

[Inoviorulez]

Very good article about RNAi therapeutics changing the future in medicine, was a good read. http://seekingalpha.com/article/1808312-3-potential-game-changers-in-the-biotech-industry?source=yahoo

[surf1944]

7:02AM Alnylam Pharma reports positive clinical results -- with up to 94% knockdown of serum transthyretin -- for ALN-TTRsc; Multiple doses of aln-ttrsc found to be generally safe and well tolerated in phase I study (ALNY) 57.25 : Key Points:

ALN-TTRsc clinical activity establishes new benchmark for consistent ttr knockdown of ~90%.
Multiple doses of aln-ttrsc found to be generally safe and well tolerated in phase i study.
Results Establish human translation of Alnylam's proprietary galnac-sirna conjugate platform for subcutaneous administration of RNAi Therapeutics with wide therapeutic index
Company to host conference call at 8:00 a.m. today to discuss clinical results.
Co announced positive interim results from its Phase I clinical trial of ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting the transthyretin gene for the treatment of TTR-mediated amyloidosis. The data are being presented today at the Heart Failure Society of America 17th Annual Scientific Meeting being held September 22 -- 25, 2013 in Orlando, Fla. Results show that ALN-TTRsc administration led to robust, consistent, and statistically significant knockdown of serum TTR protein levels of up to 94%. In addition, knockdown of TTR, the disease causing protein in ATTR, was found to be rapid, dose dependent, and durable. To date, ALN-TTRsc has been found to be generally safe and well tolerated in this study.

In addition, knockdown of TTR, the disease causing protein in ATTR, was found to be rapid, dose dependent, and durable. To date, ALN-TTRsc has been found to be generally safe and well tolerated in this study. These human data are the first to be presented for Alnylam's proprietary GalNAc-siRNA conjugate delivery platform, enabling subcutaneous dosing of RNAi therapeutics with a wide therapeutic index, and demonstrate human translation for this platform. Moreover, these results establish a new benchmark for consistent TTR knockdown of approximately 90% for RNA therapeutics in development for the treatment of ATTR.

ALN-TTRsc, which is being developed for the treatment of FAC, is a subcutaneously administered RNAi therapeutic that comprises an siRNA conjugated to a GalNAc ligand that enables receptor-mediated delivery to the liver. ALN-TTRsc is the first GalNAc-siRNA -- and the first subcutaneously delivered systemic RNAi therapeutic -- to enter clinical development stages. Alnylam is also developing ALN-TTR02, an intravenously administered RNAi therapeutic targeting TTR for the treatment of ATTR patients with FAP.

The Phase I trial of ALN-TTRsc is being conducted in the U.K. as a randomized, double-blind, placebo-controlled, single- and multi-dose, dose-escalation study, enrolling up to 40 healthy volunteer subjects. The primary objective of the study is to evaluate the safety and tolerability of single and multiple doses of subcutaneously administered ALN-TTRsc.

Interim data from the 28 subjects enrolled and analyzed in this study to date showed that single- and multi-dose administration of ALN-TTRsc resulted in rapid, dose-dependent, consistent, and durable knockdown of serum TTR levels. In the multi-dose cohorts, there was a statistically significant knockdown of serum TTR at doses of 2.5 mg/kg, 5.0 mg/kg, and 10.0 mg/kg as compared to placebo.

In 2012, Alnylam entered into an exclusive alliance with Genzyme, a Sanofi company, to develop and commercialize RNAi therapeutics, including ALN-TTR02 and ALN-TTRsc, for the treatment of ATTR in Japan and the broader Asian-Pacific region. Alnylam plans to develop and commercialize the ALN-TTR program in North and South America, Europe, and rest of the world.

[pete7]

Looking good soon this will fly

[Nickw]

Interest points discussed at JMP Securities 2013 Healthcare Conference....

http://www.earningsimpact.com/Transcript/82422/ALNY/Alnylam-Pharmaceuticals%2c-Inc----JMP-Securities-2013-Healthcare-Conference

[surf1944]

8:01AM Alnylam Pharma presents key pre-clinical proof-of-concept data for ALN-AS1; RNAi therapeutics targeting ALAS-1 completely block production of toxic heme biosynthesis intermediates that cause symptoms and disease pathology (ALNY) 27.21 : Co announced that it has presented key pre-clinical proof-of-concept data from its RNAi therapeutic program targeting aminolevulinate synthase-1 (ALAS-1) for the treatment of porphyria including acute intermittent porphyria. Specifically, Alnylam scientists and collaborators at the Icahn School of Medicine at Mount Sinai in New York City presented data from pre-clinical models of the human disease showing that RNAi therapeutics targeting ALAS-1 can completely block the abnormal production of toxic intermediates of the heme biosynthesis pathway that cause the symptoms and disease pathology of AIP. Alnylam's AIP drug candidate, ALN-AS1, is part of the co's "Alnylam 5x15" product development and commercialization strategy, in which the co aims to advance five genetic disease target programs into clinical development, including programs in late stages, by the end of 2015.

Prophylactic administration of an ALAS-1 specific siRNA completely protected mice from phenobarbital-induced up-regulation of hepatic ALAS-1 mRNA and the resulting accumulation of the neurotoxic ALA and PBG heme biosynthesis precursors. This protective effect was dose responsive and durable, with a single dose administration resulting in a protective effect that lasted for at least two weeks. Further, in a treatment model, a single dose of ALAS-1 siRNA rapidly reduced the high levels of plasma ALA and PBG that were elevated during a phenobarbital-induced acute attack. Further, preliminary comparative studies show that ALAS-1 siRNA administration was more effective than heme administration in the treatment of an acute attack. Finally, the company presented results from its ongoing GalNAc-siRNA conjugate efforts enabling subcutaneous dose administration. In particular, a prototype GalNAc-siRNA targeting ALAS-1 was shown to be effective in blocking ALA and PBG production in both prophylactic and treatment models of AIP. The company is on track to designate a GalNAc-siRNA development candidate, ALN-AS1, in late 2013 resulting in an IND filing in 2014.

[surf1944]

Alnylam Pharmaceuticals' CEO Discusses Q4 2012 Results - Earnings Call Transcript:

http://seekingalpha.com/article/1167151-alnylam-pharmaceuticals-ceo-discusses-q4-2012-results-earnings-call-transcript?source=yahoo

[Gimmysomeofdat22]

Will RGLS have any affect from ALNY shooting through the roof, or will most of the support come from the two canididates they are supposed to choose this year? Any good info about what's going to happen with them would be great.

[surf1944]

8:01AM Alnylam Pharma presents new pre-clinical data on RNAi Therapeutics for the treatment of Alpha-1 Antitrypsin (AAT) Deficiency; single intravenous dose of the drug resulted in 90% knockdown of liver mRNA and a greater than 80% decrease in serum AAT at 48 hours post-dose (ALNY) 16.94 : ALN-AAT is a new RNAi therapeutic program for the treatment of liver disease associated with AAT deficiency. New data presented at the Liver Meeting are based on an AAT-targeting siRNA formulated in a lipid nanoparticle (LNP). The AAT siRNA was administered at doses ranging from 0.03 to 1.0 mg/kg in mice overexpressing a human Z-AAT transgene, resulting in robust, dose-dependent silencing of the target mRNA and protein. Specifically, a single intravenous dose of the drug resulted in 90% knockdown of liver mRNA and a greater than 80% decrease in serum AAT at 48 hours post-dose. Furthermore, a 90% reduction in soluble protein monomers in the liver was observed at 1.0 mg/kg, with an 80% reduction seen at 0.3 mg/kg. In addition, in long-term dosing studies, in which transgenic mice overexpressing Z-AAT were dosed every other week for 12 weeks at 0.3 mg/kg, ALN-AAT resulted in a 45% reduction of pathogenic protein polymers and a significant decrease in the size and number of AAT globules in hepatocytes. Long-term dosing also significantly decreased hepatocyte proliferation and liver collagen levels, known markers of liver dysfunction and fibrosis, respectively. Further, ALN-AAT administration resulted in marked improvements in hepatocyte cellular morphology as assessed by electron microscopy. Finally, 98% suppression of liver mRNA and serum protein was observed 48 hours after a single dose of the drug in transgenic mice that had fibrotic livers, illustrating key pre-clinical proof of concept for RNAi-mediated treatment in diseased livers. Alnylam has also identified a GalNAc-siRNA targeting AAT that enables subcutaneous dose administration for further development.

[surf1944]

8:02AM Alnylam Pharma and collaborators publish new pre-clinical results on Ex Vivo Applications of RNAi to enhance dendritic cell vaccines for Cancer says 'Ex vivo treatment with siRNA was well tolerated by the isolated DC (ALNY) 17.94 : Co announced that NAi Silencing of PD-1 Ligands Significantly Boosts Dendritic Cell Immunogenicity Toward Tumor Antigens. The new results describe development of a clinical-grade DC vaccine with improved immunogenic potential. Potent siRNA were designed and synthesized toward PD-L1 and PD-L2, key co-inhibitory proteins expressed on antigen-presenting cells that strongly limit activation of T-cells needed for a potent immune response to the tumor. Specifically, lipid nanoparticle (LNP)-formulated siRNA targeting PD-L1 and PD-L2 mediated efficient and specific silencing of PD-L1 and PD-L2 expression on human monocyte-derived DC isolated from healthy donors. Ex vivo treatment with siRNA was well tolerated by the isolated DC, with no measurable effect on phenotype or migratory capacity. Further, siRNA-treated DC were loaded by electroporation with mRNA encoding minor histocompatibility antigen (MiHA) to allow long-lasting presentation of antigenic peptides expressed by malignant cells. The combined LNP siRNA transfection electroporation protocol was found to be well tolerated by the isolated DC. The resulting PD-L silenced, MiHA-expressing DCs were shown to have a significantly enhanced ability to stimulate antigen-specific CD8+ T cell responses in cells from transplanted cancer patients ex vivo. This novel RNAi approach has potential implications for the treatment of cancer and chronic viral infections, where an improvement in DC vaccine potency is needed

[Tim Lento]

I was a little early.

Check out my trade from yesterday here: http://bit.ly/MyTradeList

[surf1944]

8:02AM Alnylam Pharma and Ascletis form strategic collaboration to develop ALN-VSP, an RNAi therapeutic for the treatment of liver cancers; partnership is focused on developing ALN-VSP for hepatocellular carcinoma in China (ALNY) 12.30 : Co and Ascletis Pharmaceuticals, a privately held US-China joint venture pharmaceutical co, announced that they have formed a strategic collaboration for the development of ALN-VSP, a first-in-class, systemically delivered RNAi therapeutic for the treatment of liver cancers including hepatocellular carcinoma (HCC). This collaboration provides Ascletis with the exclusive rights to develop and commercialize ALN-VSP in China including Hong Kong, Macau, and Taiwan. Alnylam will retain all rights in the rest of the world, and is eligible to receive milestones and royalties based on product sales. Ascletis has received an exclusive license from Alnylam to develop and commercialize ALN-VSP in China including Hong Kong, Macau, and Taiwan. The initial focus will be on advancing ALN-VSP into a Phase II study for the treatment of HCC. Ascletis will diligently advance ALN-VSP, and as the program progresses, Ascletis will pay Alnylam development and commercial milestones and royalties on net sales in the Ascletis territory. Alnylam retains all rights to develop and commercialize the product in the rest of the world. Alnylam may use the data generated in China by Ascletis under this strategic collaboration for development of ALN-VSP in the rest of the world, and Ascletis may potentially receive sublicense payments based on any such future partnerships.

[Pyckstocks]

ALNY Alnylam Receives Orphan Drug Designation from U.S. Food & Drug Administration for ALN-TTR02, an RNAi Therapeutic for the Treatment of Transthyretin-Mediated Amyloidosis (ATTR)

CAMBRIDGE, Mass., Jun 19, 2012 (BUSINESS WIRE) -- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that the U.S. Food & Drug Administration (FDA) has provided Orphan Drug Designation to ALN-TTR02 as a therapeutic for the treatment of familial amyloidotic polyneuropathy (FAP), one of the predominant clinical manifestations of transthyretin (TTR)-mediated amyloidosis (ATTR).
"We are very pleased to have received Orphan Drug Designation from the FDA for ALN-TTR02, the lead effort in our 'Alnylam 5x15' product strategy. We believe RNAi therapeutics represent a novel and exciting approach for ATTR patients and have great potential to make a meaningful impact in the treatment of this devastating disease," said Saraswathy (Sara) Nochur, Ph.D., Vice President, Regulatory Affairs and Quality Assurance at Alnylam. "We look forward to sharing Phase I clinical data from our ALN-TTR02 program early in the third quarter, and, assuming continued positive results, we plan to advance to a pivotal trial in 2013. Alnylam is committed to bringing this high impact medicine to patients afflicted with ATTR."

The FDA Office of Orphan Products Development (OOPD) mission is to advance the evaluation and development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions. OOPD provides incentives for sponsors to develop products for rare diseases. The Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S.

About Transthyretin-Mediated Amyloidosis

Transthyretin (TTR)-mediated amyloidosis (ATTR) is a hereditary, systemic disease caused by mutations in the TTR gene. TTR protein is produced primarily in the liver and is normally a carrier for thyroid hormones and retinol binding proteins. Mutations in TTR cause abnormal amyloid proteins to accumulate and damage body organs and tissue such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy. In its severest form, ATTR represents a major unmet medical need with significant morbidity and mortality as an orphan disease; FAP (familial amyloidotic polyneuropathy) affects approximately 10,000 people worldwide and FAC (familial amyloidotic cardiomyopathy) affects at least 40,000 people worldwide. ATTR patients with FAP have a mean life expectancy of five to 15 years from symptom onset and the only treatment options for early stage disease are liver transplantation and tafamidis (approved in Europe); as a result there is a significant need for novel therapeutics to treat patients who have inherited mutations in the TTR gene.

About ALN-TTR Program

ALN-TTR02 is a systemically delivered RNAi therapeutic being developed for the treatment of ATTR. Alnylam has completed enrollment in a Phase I trial with ALN-TTR02 and expects to present data early in the third quarter of 2012. The company recently initiated a Phase II trial in Europe with ALN-TTR02 aimed at evaluating safety, tolerability, and potential clinical activity of multiple once-monthly doses of ALN-TTR02 in ATTR patients. Specifically, the study will evaluate the potential clinical activity of ALN-TTR02 based on measurement of serum levels of TTR, the disease-causing protein in patients with ATTR. ALN-TTR02 is formulated in a proprietary second-generation lipid nanoparticle technology, using the "MC3" lipid. Assuming positive results from the Phase II study, Alnylam expects to start a pivotal trial for ALN-TTR02 in 2013. Alnylam also plans to advance ALN-TTRsc, which utilizes a GalNAc-conjugate delivery approach and subcutaneous dose administration. Alnylam's goal is to advance ALN-TTRsc to an investigational new drug (IND) filing in the second half of 2012 with data in the first half of 2013.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding 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 once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery 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 biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific 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 leading the translation of RNAi as a new class of innovative medicines with a core focus on RNAi therapeutics for the treatment of genetically defined diseases, including ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, ALN-APC for the treatment of hemophilia, and ALN-TMP for the treatment of hemoglobinopathies. As part of its "Alnylam 5x15(TM)" strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in clinical development, including programs in advanced stages, on its own or with a partner by the end of 2015. Alnylam has additional partner-based programs in clinical or development stages, including ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection, ALN-VSP for the treatment of liver cancers, and ALN-HTT for the treatment of Huntington's disease. The company's leadership position on RNAi therapeutics and intellectual property have enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. In addition, Alnylam and Isis co-founded Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics; Regulus has formed partnerships with GlaxoSmithKline and Sanofi. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for applications in biologics manufacturing, including recombinant proteins and monoclonal antibodies. Alnylam's VaxiRNA(TM) platform applies RNAi technology to improve the manufacturing processes for vaccines; GlaxoSmithKline is a collaborator in this effort. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 100 peer-reviewed papers, including many in the world's top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, and Cell. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit www.alnylam.com.

About "Alnylam 5x15(TM)"

The "Alnylam 5x15" strategy, launched in January 2011, establishes a path for development and commercialization of novel RNAi therapeutics to address genetically defined diseases with high unmet medical need. Products arising from this initiative share several key characteristics including: a genetically defined target and disease; the potential to have a major impact in a high unmet need population; the ability to leverage the existing Alnylam RNAi delivery platform; the opportunity to monitor an early biomarker in Phase I clinical trials for human proof of concept; and the existence of clinically relevant endpoints for the filing of a new drug application (NDA) with a focused patient database and possible accelerated paths for commercialization. By the end of 2015, the company expects to have five such RNAi therapeutic programs in clinical development, including programs in advanced stages, on its own or with a partner. The "Alnylam 5x15" programs include ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-APC for the treatment of hemophilia, ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, and ALN-TMP for the treatment of hemoglobinopathies. Alnylam intends to focus on developing and commercializing certain programs from this product strategy itself in the United States and potentially certain other countries; the company will seek development and commercial alliances for other core programs both in the United States and in other global territories.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, statements regarding Alnylam's views with respect to the potential for RNAi therapeutics, including ALN-TTR02 and ALN-TTRsc, its expectations with respect to the timing and success of its clinical trials for ALN-TTR02, its expectations regarding the reporting of data from its ALN-TTR02 clinical trials, and Alnylam's expectations regarding its "Alnylam 5x15" product strategy, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Alnylam's ability to discover and develop novel drug candidates, successfully demonstrate the efficacy and safety of its drug candidates, including ALN-TTR02 and ALN-TTRsc, the pre-clinical and clinical results for these product candidates, which may not support further development of such product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials for such product candidates, obtaining, maintaining and protecting intellectual property, obtaining regulatory approval for products, competition from others using technology similar to Alnylam's and others developing products for similar uses, and Alnylam's ability to establish and maintain strategic business alliances and new business initiatives, as well as those risks more fully discussed in the "Risk Factors" section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking 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 not assume any obligation to update any forward-looking statements.

SOURCE: Alnylam Pharmaceuticals

CONTACT:
Alnylam Pharmaceuticals, Inc. Cynthia Clayton, 617-551-8207 Vice President, Investor Relations and Corporate Communications or Spectrum (Media) Amanda Sellers, 202-955-6222 x2597
Copyright Business Wire 2012

[surf1944]

8:03AM Alnylam Pharma collaborators publish new pre-clinical results with an RNAi therapeutic approach for inducing endogenous erythropoiesis for the treatment of anemia (ALNY) 11.02 : Co announced the publication of new pre-clinical results in the journal Blood that describe targeting the egg-laying nine homolog (EglN) pathway for the treatment of anemia using RNAi therapeutics. The new findings show that activation of hepatic erythropoietin production using systemically delivered siRNA targeting EglN prolyl hydroxylases leads to improved red blood cell production in pre-clinical models of anemia. New approaches that induce endogenous mechanisms for erythropoiesis could address unmet medical needs in the management of anemia in patients who are refractive to current therapies. Specifically, data showed that a systemically administrated RNAi therapeutic targeting the EglN family of proteins achieved dose-dependent silencing of EglN genes in vivo in animal models. The research showed that EglN silencing resulted in sustained increase in circulating erythropoietin that was generated specifically by the liver. The induction of endogenous liver erythropoietin expression recapitulates a developmental pathway for red blood cell production known to exist in the fetus. This increase in erythropoietin was detectable out to two weeks after administration of a single dose of the RNAi therapeutic and was associated with a sustained increased in red blood cell parameters including reticulocyte count, hemoglobin and hematocrit. Further, RNAi therapeutics targeting the EglN pathway were found to significantly correct anemia in models of both renal failure and chronic inflammation. Other changes observed with RNAi therapeutic targeting EglNs, such as decreased production of hepcidin, were also demonstrated and could enhance the effectiveness of endogenous erythropoiesis by improving iron mobilization, thereby lowering the circulating erythropoietin levels needed to promote red blood cell production

[surf1944]

8:02AM Alnylam initiates Phase II clinical trial of ALN-TTR02 (ALNY) 11.04 : Co announced that it has completed enrollment in its Phase I trial with ALN-TTR02, an RNAi therapeutic targeting the transthyretin (TTR) gene for the treatment of TTR-mediated amyloidosis (ATTR). Alnylam also announced today that it has initiated a Phase II trial with ALN-TTR02 aimed at evaluating clinical activity, safety, and tolerability of multiple once-monthly doses of ALN-TTR02 in ATTR patients. Specifically, the study will evaluate the clinical activity of ALN-TTR02 based on measurement of serum levels of TTR, the disease-causing protein in patients with ATTR. ALN-TTR02 utilizes the company's proprietary second-generation lipid nanoparticle (LNP) delivery technology using the "MC3" lipid. The company expects to present data from the Phase I trial early in the third quarter of 2012.

[mlkrborn]

Alnylam Pharma announces top-line results of Phase IIb clinical trial of ALN-RSV01; says study in RSV-infected lung transplant patients narrowly misses primary 'Intent-to-Treat' endpoint (ALNY) 10.12 : Co announced today top-line results from a Phase IIb trial with ALN-RSV01 for the treatment of respiratory syncytial virus infection in lung transplant patients. The primary endpoint of the study was the incidence of new or progressive bronchiolitis obliterans syndrome at 180 days after RSV infection. The study missed the primary endpoint of reduced BOS in an "intent-to-treat" analysis of confirmed RSV infected patients, but achieved statistically significant reductions in prospectively defined analyses of ITTc patients with their "last observation carried forward" with a p-value of 0.028, and of ITTc patients treated "per protocol" with a p-value of 0.025. In all analyses, ALN-RSV01 treatment was associated with a clinically meaningful treatment effect, with a reduction of over 50% in the incidence of day 180 BOS as compared with placebo. Top-line results are detailed in the table below. In the ITTc analysis, ALN-RSV01 narrowly missed the primary endpoint of new or progressive BOS at 180 days. ALN-RSV01 treatment was associated with a statistically significant reduction in the incidence of day 180 BOS in the prospectively defined LOCF and PP analyses. In all analyses, treatment with ALN-RSV01, as compared with placebo, was associated with a clinically meaningful reduction in the incidence of BOS with a treatment effect ranging from approximately 54% to 65%. Following central laboratory testing by PCR analysis, 10 patients could not be confirmed as infected for RSV; these patients happened to include nine patients randomized to receive placebo and one patient randomized to receive ALN-RSV01. ALN-RSV01 was found to be generally safe and well tolerated in the study, with a comparable incidence of reported adverse events in placebo and study drug treatment arms. There were three deaths in the study, two in placebo and one in ALN-RSV01, all of which were determined to be unrelated to treatment. Additional study results are expected to be presented at the European Respiratory Society Annual Congress taking place September 1-5, 2012 in Vienna.

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7:02AM Alnylam Pharma presents final results from a Phase I clinical trial of ALN-TTR01; data shows that administration of ALN-TTR01 resulted in statistically significant reductions in serum TTR protein levels, including both wild-type and mutant TTR protein, in ATTR patients (ALNY) 10.60 : Co announced final results from its completed Phase I clinical trial with ALN-TTR01, an RNAi therapeutic targeting transthyretin for the treatment of TTR-mediated amyloidosis. The data were presented at the XIII International Symposium on Amyloidosis held May 6-10, 2012 in Groningen, The Netherlands. Data from this study show that administration of ALN-TTR01 resulted in statistically significant reductions in serum TTR protein levels, including both wild-type and mutant TTR protein, in ATTR patients. Knockdown of TTR, the disease-causing protein, was found to be dose dependent, rapid, and durable after just a single dose. The full time course for TTR knockdown reveals the potential for once monthly or possibly once every other monthly dose regimens in further studies. ALN-TTR was found to be generally safe and well tolerated in this study. "We believe these data with ALN-TTR01 provide key human proof of concept as we advance ALN-TTR02 as our 'go-to-market' RNAi therapeutic for the treatment of ATTR, a debilitating orphan genetic disease. ALN-TTR02 uses our proprietary second-generation LNP formulation which has demonstrated markedly improved potency in human clinical studies, and we look forward to presenting results from an ongoing Phase I clinical study in the third quarter of 2012. Alnylam is committed to bringing this high impact medicine to patients afflicted with ATTR." ALN-TTR01 was found to be generally safe and well tolerated in ATTR patients. Mild-to-moderate acute infusion reactions were observed in 5 of 24 (20.8%) patients receiving ALN-TTR01 and were readily managed by slowing of the infusion rate where necessary. There were no significant increases in liver function test parameters. All patients on study drug completed the study; there were no discontinuations except for one patient in the placebo group who underwent elective hospitalization for a liver transplant, and was scored as a serious adverse event unrelated to study drug. Co expects to start a Phase II study of ALN-TTR02 in ATTR patients in the second half of 2012 and expects to start pivotal studies in 2013.

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Not even mentioned in the PR by ALNY is Tekmira's role in producing ALN-PCS. This is not surprising since the two companies are embroiled in lawsuits, but TKMR was quick to produce its own spin on the ALNY news.

Tekmira's LNP Technology Enables Alnylam's Positive ALN-PCS Clinical Data4-20-12 10:51 AM EDT

VANCOUVER, British Columbia, April 20, 2012 (GLOBE NEWSWIRE) -- Tekmira Pharmaceuticals Corporation (Nasdaq:TKMR) (TSX:TKM), a leading developer of RNA interference (RNAi) therapeutics, today reported that Alnylam Pharmaceuticals, Inc. presented positive clinical results from its Phase 1 clinical trial of ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of severe hypercholesterolemia, which utilizes Tekmira's lipid nanoparticle (LNP) technology and is manufactured by Tekmira.......

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Alnylam Reports Positive Clinical Results for ALN-PCS, an RNAi Therapeutic Targeting PCSK9 for the Treatment of Severe Hypercholesterolemia

– PCSK9 Synthesis Inhibitor Achieves up to 84% Knockdown of PCSK9 and 50% Lowering of LDL Cholesterol in Single Dose, Statin-Free Phase I Trial –

– New Results Highlight Continued Improved Efficacy and Safety for Alnylam Second-Generation Lipid Nanoparticles (LNP) –
Business WirePress Release: Alnylam Pharmaceuticals, Inc. – 34 minutes ago

CAMBRIDGE, Mass.--(BUSINESS WIRE)--

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY - News), a leading RNAi therapeutics company, announced today positive results from its Phase I clinical trial of ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of severe hypercholesterolemia. ALN-PCS is a PCSK9 synthesis inhibitor that reduces intracellular and extracellular levels of PCSK9 resulting in lowered plasma levels of low-density lipoprotein cholesterol (LDL-C), or “bad” cholesterol. The new data were presented at the American Heart Association’s Arteriosclerosis, Thrombosis and Vascular Biology 2012 Scientific Sessions held in Chicago. Results showed that administration of a single dose of ALN-PCS, in the absence of concomitant lipid-lowering agents such as statins, resulted in statistically significant and durable reductions of PCSK9 plasma levels of up to 84% and lowering of LDL-C of up to 50%. The new data also highlight continued improved efficacy and tolerability for Alnylam’s second-generation lipid nanoparticle (LNP) delivery technology.

“We are very excited by these new ALN-PCS data that demonstrate robust clinical efficacy for this PCSK9 synthesis inhibitor. Indeed, we believe the unique mechanism of action for ALN-PCS, which inhibits the synthesis of PCSK9 in liver cells thereby reducing both its intracellular and extracellular functions, provides a differentiated strategy for PCSK9 antagonism. This mechanism of action for ALN-PCS results in potent and durable LDL-C reductions and consistent clinical activity across a wide range of baseline PCSK9 plasma levels, including individuals with very high PCSK9 levels,” said Akshay K. Vaishnaw, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Alnylam. “These new results show very robust, statistically significant, and dose-dependent lowering of both PCSK9 and LDL-C levels in a single dose study performed in the absence of statin co-administration. In addition, ALN-PCS treatment was well tolerated at all dose levels studied to date indicating the potential to even further dose escalate in future studies.”

“Cardiovascular disease remains the leading cause of mortality worldwide, with elevated LDL-C a major modifiable risk factor. A substantial number of patients cannot achieve target LDL levels with current drugs, such as statins, and it is clear that new therapeutic options are needed,” said Daniel J. Rader, M.D., Director of Preventive Cardiovascular and Associate Director of the Institute for Translational Medicine and Therapeutics at University of Pennsylvania. “As a key regulator of the LDL receptor, liver-expressed PCSK9 is one of the most important and best validated new targets in molecular medicine for the treatment of hypercholesterolemia. An RNAi therapeutic targeting PCSK9 expression in the liver has the potential to rapidly and durably lower LDL cholesterol, thereby reproducing the effects observed in loss-of-function human mutations that are associated with significant clinical benefit. I am very encouraged by the ALN-PCS data generated to date and look forward to continued studies that highlight the unique mechanistic approach of PCSK9 synthesis inhibitors, including the potential magnitude and durability of LDL-C response when ALN-PCS is co-administered with statins.”

The Phase I study was conducted as a randomized, single-blind, placebo-controlled, single-ascending dose study in healthy volunteer subjects with elevated baseline LDL-C (greater than 116mg/dL). The primary objective of the study was to evaluate the safety and tolerability of a single dose of ALN-PCS. Secondary objectives of the study included assessment of pharmacodynamic effects of the drug on plasma PCSK9 protein levels and evaluation of clinical efficacy as measured by LDL-C levels. A total of 32 subjects were enrolled into six sequential dose cohorts ranging from 0.015 to 0.400 mg/kg in a 3:1 randomization of drug to placebo.

In this study, administration of ALN-PCS resulted in rapid, dose-dependent, and durable reductions in LDL-C of up to 50% relative to baseline and placebo, with a statistically significant mean reduction of 41% (p<0.01) at the 0.400 mg/kg dose level. In addition, ALN-PCS administration resulted in rapid, dose-dependent, and durable knockdown of PCSK9 protein levels in plasma of up to 84% relative to baseline and placebo, with a statistically significant mean reduction of 68% in the highest dose group of 0.400 mg/kg (p<0.0001). There was also a dose-dependent increase in the proportion of subjects who achieved “target” levels of LDL-C of less than 100 mg/dL (p<0.05). The effects of a single dose of ALN-PCS support a once-monthly dose administration regimen for future studies. Importantly, ALN-PCS demonstrated consistent clinical activity toward both PCSK9 and LDL-C independent of baseline levels of PCSK9, highlighting the unique mechanism of action for a PCSK9 synthesis inhibitor.

ALN-PCS was shown to be safe and well tolerated in this study and there were no serious adverse events related to study drug administration. There were no drug-related discontinuations and no liver enzyme elevations. There was also no significant change compared to baseline in levels of high-density lipoprotein (HDL), or “good” cholesterol, consistent with the phenotype observed in human PCSK9 loss-of-function mutations.

“These data mark yet another important milestone in our overall ‘Alnylam 5x15’ efforts, as they demonstrate continued safety, tolerability, and robust clinical efficacy of an RNAi therapeutic targeting a liver-expressed disease gene utilizing our second generation lipid nanoparticle delivery technology,” said Barry Greene, President and Chief Operating Officer of Alnylam. “In particular, these new data strongly support continued advancement of ALN-TTR02, an RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR), which employs the same second generation LNP delivery formulation as ALN-PCS. Dosing in our ALN-TTR02 clinical study has recently been initiated and we are on track to report data in the third quarter of this year.”

ALN-PCS is an RNAi therapeutic that utilizes proprietary second-generation LNP technology with the MC3 lipid. This study represents the first human results with this delivery platform. The same RNAi delivery formulation is being used for Alnylam’s ALN-TTR02 program, an RNAi therapeutic targeting TTR for the treatment of ATTR.

The presentation of these data can be found on Alnylam’s website at www.alnylam.com/capella.

Dr. Rader serves as a consultant on Alnylam’s ALN-PCS program, and Alnylam and Dr. Rader collaborate on research for which Alnylam provides materials.

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Future Trends In RNAi Drug Delivery

http://seekingalpha.com/article/462251-future-trends-in-rnai-drug-delivery?source=yahoo

For those interested in RNAi therapeutics, it would be wise to pay attention to every development related to delivery technology. The concept and clinical results behind RNAi are compelling, but perhaps something equally exciting is that there is still room to grow. With human proof of concept demonstrated, RNAi companies can reformulate with new delivery technology and enjoy the benefits. This article will examine next generation LNP delivery the pipeline.

LNP technology for indications involved with the liver is the most mature delivery system within RNAi therapeutics. Current LNP (lipid nanoparticle) technology is in its 2nd generation (such as ALN-PCS, ALN-TTR02) which has ~100-fold increased potency and better safety than 1st generation (such as ALN-VSP, ALN-TTR1) offerings.

One of the issues with the current 2nd generation LNP is that they have long elimination half-lives in plasma and tissues. It is suspected that they might accumulate over time and lead to cytotoxicity in target cells with chronic dosing. Specifically, they end up building up in the liver and spleen.

The idea behind the new 3rd generation LNP technology being researched by Alnylam (ALNY) is to create a rapidly eliminating LNP formulation (reLNP). The idea behind reLNP is to have them be rapidly biodegradable so this accumulation can not occur. Observe these preclinical results of how these rapidly eliminating LNP are eliminated in the plasma, liver and spleen. It looks like 2 reLNP lipids are being evaluated with different elimination half-lives. I assume that 2 reLNPs are being researched so further experimentation can find the sweet spot for therapeutic application.

In addition to this change, Alnylam is investigating subcutaneous (abbreviated SC) administration at smaller (20%), but more frequent intervals as opposed to one bigger dose. This has shown a greater therapeutic index in preclinical animal models. In my opinion, SC administration was always assumed to be better but it is much less convenient for the patient. Never the less, it seems as though Alnylam is warming up to the idea and Tekmira (TKMR) has also chose to do one of their two TKM-PLK1 phase 1 trials subcutaneously also. SC administration may be a trend for RNAi for more serious conditions where it can be justified.

Its interesting to note that Alnylam did the SC reLNP testing with ALN-TTR. They state their plans are to bring this 3rd generation LNP in the clinic in 2013.

Take a look at the comparison between 1st-3rd generation LNP.

The question on my mind is does these rapidly eliminating LNP fall under Tekmira's IP? Tekmira has a patent on all LNP formulations, so reason says that these reLNPs fall under this patent. Upon review of Tekmira's patent and subsequent review of the reLNP information provided by Alnylam, I can find no reason why it does not fall under this patent.

In the context of Tekmira and Alnylam litigation, I can see Alnylam possibly wanting to shift their pipeline offerings from being MC3 dependent to these new generation technologies. MC3 may prove to be toxic (figuratively speaking) as AlCana has been admitted stealing documents from Tekmira then collaborating with Alnylam on the technology. Tekmira has also filed an injunction to prohibit use of MC3 and there is a decent chance it might be granted in my view.

I suspect matters related to delivery expenses may be part of the reason extra funds were needed with their recent capital raise. I cant help but wonder what they intend to do with their pipeline in regards to 3rd generation LNP. Will they redo part (all?) of their Phase I with 3rd generation? Higher doses may be needed with some of their offerings and a formulation with increased safety/efficiency would be desirable.

I have less information about 3rd generation offerings by Tekmira but they are also working on them. In their news reliese for their ALDH2 program, they announced it would be used with next generation LNP formulation that has demonstrated better potency and greater therapeutic index than all previous LNP formulations. I have not seen any specific data on Tekmira's 3rd generation LNP and would love to get my hands on the information. If any readers have any information from Dr. MacLachlan's presentation titled "Progress in the Development of Lipid Nanoparticle siRNA-Based Drugs" from the Asia TIDES Oligonucleotide and Peptide Technology and Product Development Conference, please send me the information.

Much of the information regarding reLNP can be viewed here. I would love for my articles to be more interactive in the comments section, so please feel free to add anything.

[mlkrborn]

stox sale @10.75
Alnylam Pharma prices 7.5 mln shares of commond stock at $10.75 (ALNY) 10.98 :