Top 5 Game Changing Technologies

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Top 5 Game-Changing Drug Delivery

Technologies

October 26, 2010 10:14am ET | By Howard Lovy

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It is not enough to invent a potential new miracle drug. If there is no

efficient way to get the therapeutic to exactly where it is needed,

without harming healthy cells, then the drug is no "miracle" at all. If

the drug produces so many unpleasant side effects that patient

compliance becomes an issue, development is far from over. This

remains true not only with drugs that are in development, but even

those that are already on the market. Just because it has been

approved by the FDA and is being successfully and safely used by

consumers does not mean development of that drug is over.

What new delivery methods bring to the table are not only unique

ways to continue innovating even after the therapeutic goes off patent,

but the ability to give relief to patients who may be suffering from

drug side effects.

Drug delivery is not just about getting a therapeutic to its target. It's

also about finding new materials that can make the journey without

interfering with the drug. One of the major problems facing the

pharmaceutical industry today is the poor solubility of drugs. So,

drugmakers tack on compounds to make it more soluble.

Unfortunately, patients read about the side-effects of those soluble


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compounds in the often-mocked, ubiquitous "fine print" that drug

companies are forced to include in their commercials. The challenge is

to find materials that make those side effects disappear.

The drug delivery industry is not only alive and well, but could be

booming in the near future. Here are the top five technologies catchingdrugmakers' attention.

1. Oral Thin Films2. Microneedles3. Slow release/extended

release for addiction4. Aerosol5. Liposomes

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Oral Thin Films: Game-Chaning Drug

Delivery TechnologiesOctober 26, 2010 10:12am ET | By Howard Lovy



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What are they? Oral thin films are postage-stamp-sized versions of

existing drugs that dissolve under the tongue or against the cheek--

sort of a high-tech version of the breath strips you can buy at your

local convenience store. They can carry very low doses of prescription

that are highly uniform and larger doses up to 80 mg. They are

emerging as a trend in drug delivery in treatments for everything from

Alzheimer's disease to diabetes to erectile dysfunction.

What makes it groundbreaking? Oral thin films are easy to swallow

without water, especially for pediatric, geriatric and neurodegenerative

disease patients where proper dosing can be difficult. In chronic care,

thin films give caregivers the ability to medicate regularly without

injections. They are also a means of differentiated marketing for off-

patent drugs.

Who's working on it:

Monosol Rx markets PharmFilm, which the FDA has given the go-

ahead for an opioid-dependence drug, Suboxone, which is

expected to hit the market after October. The drug was

developed jointly by MonoSol Rx and Reckitt Benckiser

Pharmaceuticals. MonoSol Rx has a continuing mission to take

existing drugs and formulate thin-film versions of them. MonoSol

RX has also collaborated, since 2008, with Midatech Group, a

UK-based company that designs and synthesizes nanoparticle-based proteins and peptides for therapeutic delivery using

pharmaceutical films. Report | Report

Applied Pharma Research (APR) and its development partner

Labtec have entered into an exclusive licensing agreement with

Ferrer Internacional, which will promote and distribute Donepezil

Oral Dispersible Film (ODF) in Spain, Portugal and Germany.

Donepezil ODF is a thin film formulation for symptomatic

treatment of Alzheimer's disease and other types of

dementia. Report

IntelGenx is developing a thin oral film that delivers INT007, whichis the bioequivalent to phosphodiesterase type 5 that is found in

leading ED tablets Viagra and Cialis. IntelGenx has announced

that it's finished a study that indicates its thin film, called

VersaFilm might actually work faster than those leading ED

tablets. Report


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protect health-care workers who would run less of a risk of accidentally

poking themselves with larger needles.


China-based Suzhou Natong Bionanotechnology is developing a5 mm-square "MicroArray" patch that contains about 400 tiny

needles with possible applications in diabetes and pain relief in

addition to the eradication of zits. A product, LiteClear, is

available in China that uses the microneedles to unclog pores.

Report

Researchers from North Carolina State University think they've

found a way to deliver quantum dots into the body using tiny,

specially fabricated, hollow microneedles. Report

Researchers at Purdue University have developed a pump that can

fit in 20-micron-diameter needles, which would go on patches todeliver a wider range of medication than is now possible. Report

Georgia Tech and Emory University have tested on laboratory

animals a vaccine-delivery patch containing hundreds of

microneedles. Report

And one imaging company is developing technology that it believes

microneedle researchers need. Michelson Diagnostics, based

in the U.K., is reporting that its VivoSight OCT imaging system

was used to evaluate the performance of a new microneedle

drug delivery technology by researchers at Queen's University

Belfast. The research by Ryan Donnelly, published in theJournalof Controlled Release, shows how the VivoSight system was used

to directly image the microneedles penetrating the skin. Those

results helped evaluate how far apart the needles were spaced

and how much force is required. Report

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..

Slow release/extended release for

addiction - Game-Changing Drug


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Delivery Technologies


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What is it? This is really an extension of older technology, but new

materials are opening up new applications to enable sustained release

over long periods of time. There are many applications to slow-release

technology, but one prominent one is for addiction treatment and

prevention.

Why is it groundbreaking? All you have to do is follow the news,from your local crime report to celebrities who continuously get in

trouble with the law for failing to remain drug-free. Part of the problem

is that drugs that begin as painkillers are too easily abused and

become gateways to illegal drugs like heroin. The solution? Better drug

delivery for painkillers that get the right amount into the system to do

the job, but avoid user temptation for abuse. Opioid addicts--including

abusers of prescription drugs such as OxyContin--do not get a chance

to backslide because they do not have to think about taking the

treatment every day.


A drug called Vivitrol has received separate FDA approvals to treat

alcohol and opioid addictions through drug-delivery technology

by Alkermes called Medisorb, which enables sustained releases

over long periods of time. The company says the technology

allows us it to encapsulate small molecules, peptides and


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proteins in microspheres made of biodegradable polymers with

extended-release profiles lasting from days to months. Report

Titan Pharmaceuticals' implanted drug-delivery device helped

people fight addiction to heroin and prescription painkillers

better than a placebo, a company-funded study found. Study

participants who used Titan's Probuphine implant hadsignificantly less illicit opioid use, experienced fewer symptoms

of withdrawal and craving, stayed in treatment longer and had

greater overall improvement. Report

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Aerosol - Game-Changing Drug Delivery

Technologies





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What is it? This is not your father's nebulizer. A new range of

materials--and nanomaterials--are being developed for pulminary

delivery via aerosols, metered dose inhaler systems, dry powder


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inhalers or nebulizers. Research into lung delivery is driven by the

potential for successful gene therapy for respiratory diseases such as

cystic fibrosis.

Why is it groundbreaking? Aerosol delivery offers alternative

technologies to meds going off patent. According to a recent report inin-PharmaTechnologist, Big Pharma is biting. Recently, "three of the

world's largest industry companies" expressed interest in using a

platform developed by one company, Stirling, to create inhalable

formulations of their drugs. Studies are ongoing on the benefits of

aerosol vs. oral for treatment of TB.

Who's working on it?

Stirling is one of many companies offering alternative delivery

technologies to meds going off patent. What Stirling offers is itshigh density aerosol technology, which promises to provide the

same efficacy as drugs taken orally, but with far less active drug

content, according to the company. That, the company adds,

means fewer side effects. Report

Savara Pharmaceuticals, based in Austin, Texas, has caught the

attention of investors for its nanoscale powders--called

NanoClusters--to take the place of propellants for delivery via

oral pulmonary or nasal routes. Report

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Liposomes - Game-Changing Drug

Delivery Technologies




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What it is: Artificially made microscopic drug delivery device

consisting of a fatty membrane over a hollow "bubble."

What make it groundbreaking: This class of drug delivery device is

not new. However, recent years have seen such big improvements in

these drug-carrying "bubbles" that they might as well be considered as

new.

Who's working on them:

ThermoDox, by drug developer Celsion, was recently granted fast-

track status by the FDA for treatment of primary liver cancer.

Celsion's technology involves low heat-activated liposomes,

which the company says enables delivery of drugs directly to

cancer sites. They call them lysolipid thermally sensitive

liposomes (LTSL), and they're being billed by Celsion as "the first

in a new generation of liposomes." Report

Marina Biotech recently acquired the rights to "Smarticles"

technology from Germany's Novosom in exchange for $5 million

in common stock. "Smarticles," involve liposomes that can cross

cell membranes to deliver to the target and engage the RNA

interference pathway. They can also change its surface electric

charge to drop off its payload. Report

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Celsion's ThermoDox liver cancer trials


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get fast-tracked

August 25, 2010 1:02am ET | By Howard Lovy




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Drug developer Celsion and sufferers of primary liver cancer received

some good news from the FDA this week as the Columbia, MD-based

company's first drug, ThermoDox, was granted fast-track status.

Developed in partnership with Duke University, Celsion's technology

involves low heat-activated liposomes, which the company says

enables delivery of drugs directly to cancer sites. They call themlysolipid thermally sensitive liposomes (LTSL), and they're being billed

by Celsion as "the first in a new generation of liposomes." ThermoDox,

enhanced with LTSL, treats primary liver cancer and recurrent chest

wall breast cancer.

The specially treated liposomes concentrate at the tumor as an

external microwave device gently heats the tumor tissue to 42 degrees

Celsius over the course of 40 minutes. ThermoDox circulates through

the bloodstream, penetrating tumors through vascular leaks. The

microwave heat accentuates this leaking, opening the tumor door tomore ThermoDox. According to the company, the liposome "melts"

only when the microwave heat is present and releases the oncology

drug doxorubicin only into the tumor in high concentrations.

Celsion says its goal is to improve standard treatment options for

difficult-to-treat cancers, including non-resectable hepatocellular

carcinoma (HCC), commonly referred to as primary liver cancer. For


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liver cancer, the technique is used in conjunction with radio frequency

ablation (RFA), which uses uses extremely high temperatures of 80 to

100 degrees Celsius to ablate tumors. RFA may fail to treat the outer

margins of larger tumors since temperatures in the periphery are not

high enough to destroy the cancer cells. That's where ThermoDox

comes in.

"We are very pleased to receive the Agency's Fast-Track Designation

for ThermoDox," says CEO Michael Tardugno, in a statement. "Fast

Track Designation is an acknowledgement that HCC is a significant

unmet medical need representing a life threatening disorder. It also

recognizes the challenges facing pharmaceutical companies to develop

effective new treatments for this difficult disease."

ThermoDox is currently being evaluated under a Special Protocol

Assessment agreement with the FDA in a 600-patient global Phase IIItrial in patients with primary liver cancer. Celsion hopes to complete

patient enrollment by the end of the year.

- read the Celsion release- take a look at more info at

clinicaltrials.gov- and see a video of ThermoDox in action

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ProNAi tests 'Smarticles' delivery tech

in trials

September 22, 2010 1:40am ET | By Howard Lovy



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Kalamazoo-MI-based ProNAi Therapeutics has launched Phase I clinical

trials in Texas for its anti-tumor drug candidate, PNT2258, using a

drug delivery technology licensed by Marina Biotech.

"We are pleased to move PNT2258 into the clinic and to be able to

gain insights into the safety and promise of this novel delivery

technology," Dr. Wendi Rodrigueza, vice president of product

development at ProNAi, says in a statement.

The company says this clinical trial will test the drug on patients with

advanced solid tumors for which there are no standard therapies.

The drug-delivery technology it uses, called "Smarticles," involves

liposomes that can cross cell membranes to deliver to the target and

engage the RNA interference pathway. It can also change its surface

electric charge to drop off its payload.

As we reported at the beginning of August, Marina Biotech acquiredthe rights to the Smarticles technology from Germany's Novosom in

exchange for $5 million in common stock.

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Marina Biotech acquires RNAi delivery

technology

August 4, 2010 2:22am ET | By Howard Lovy



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Marina Biotech of Bothell, WA, has added more siRNA IP to its toybox

by acquiring the rights to technology from Germany's Novosom inexchange for $5 million in common stock.

Development of gene-silencing RNA therapeutics has been delayed for

years because of difficulties in finding a delivery device that can slip

inside a cell, precisely deliver the therapeutics, then go away

harmlessly.

In-PharmaTechnologistreports that Novosom has applied its

technology to the delivery of antisense, siRNA, LNA and other

oligonucleotides. The technology, called "Smarticles," involvesliposomes that can cross cell membranes to deliver to the target and

engage the RNA interference pathway. It can also change its surface

electric charge to drop off its payload.

- see the Marina Biotech release- read the in-PharmaTechnologist

report - a more technical description can be found on the RNAi

therapeutics blog

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Marina Biotech Acquires RNA Delivery

Assets of Novosom AG

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Posted August 4, 2010

Marina Biotech Acquires RNA Delivery Assets of Novosom AG

Patent Rights to SMARTICLES(R) Technology Strengthens Marina's

Intellectual Property Position and Further Expands Its siRNA Delivery

Technologies BOTHELL, WA, Jul 28, 2010 (MARKETWIRE via COMTEX)-- Marina Biotech, Inc. (NASDAQ: MRNAD) announced today that the

Company has acquired the intellectual property of Novosom AG of

Halle, Germany for its SMARTICLES(R) liposomal-based delivery

system in an all-stock transaction. The transaction further expands

Marina's RNA delivery platform IP estate, which now includes DiLA2

delivery platform, tkRNAi (bacterial delivery platform), peptide

nanoparticle delivery platform, and the SMARTICLES(R) liposomal

delivery platform. This acquisition significantly broadens the number of

approaches Marina may take for systemic and local delivery of its

proprietary UsiRNA therapeutics. The assets were acquired by Marina

for approximately $5 million in unregistered Marina common stock.

Additional terms of the agreement were not disclosed.

"We are pleased to have acquired the SMARTICLES(R) intellectual

property estate of Novosom," stated J. Michael French, President and

CEO of Marina Biotech. "We believe that this technology and

intellectual property estate, resulting from years of hard work and

diligent IP prosecution on the part of Novosom, is a significant addition

to our existing RNA delivery platforms and the IP estate of Marina

Biotech. We plan to take full advantage of our new IP position by

expanding our existing delivery capability to develop additional novelformulations for safe and effective systemic and local delivery of RNAi-

based therapeutics."

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The acquired Novosom patent estate represents a global portfolio


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including 42 issued or allowed patents and 31 pending patent

applications providing broad coverage for liposomal delivery

formulations, lipid compounds and nucleic acid chemistry.

"We believe the team at Marina Biotech is best positioned to further

develop and exploit the advantages of the SMARTICLES(R) siRNAdelivery platform," stated Elias Papatheodorou, Chief Executive Officer

of Novosom, AG. "The addition of this technology to the expanding

capability of Marina provides a truly unique opportunity in the sector to

advance multiple RNAi-based therapeutics to the market."

Novosom's SMARTICLES(R) define a novel class of liposomes: fully

charge-reversible particles. Novosom's liposomal vectors allow delivery

of active substance (siRNA, antisense, decoy, etc.) inside the cell

either by local or systemic administration. SMARTICLES(R) are

designed to ensure: (1) stable passage through the bloodstream and(2) release of the nucleic acid payload within the target cell where it

can engage the RNA interference pathway and exert its therapeutic

effect.

Canaccord Genuity served as Marina's financial advisor on this

transaction and Ferghana Partners Group served as Novosom's

financial advisor.

About Marina Biotech, Inc.

Marina Biotech (formerly known as MDRNA, Inc.) is a biotechnology

company, focused on the development and commercialization of

therapeutic products based on RNA interference (RNAi). Marina's

pipeline currently includes a clinical program in Familial Adenomatous

Polyposis (a precancerous syndrome) and two preclinical programs --

in hepatocellular carcinoma and bladder cancer. Marina's goal is to

improve human health through the development of RNAi-based

compounds and drug delivery technologies that together provide

superior therapeutic options for patients. Additional information about

Marina Biotech is available at http://www.marinabio.com.

Forward-Looking Statements Statements made in this news release may beforward-looking statements within the meaning of Federal Securities lawsthat are subject to certain risks and uncertainties and involve factors thatmay cause actual results to differ materially from those projected orsuggested. Factors that could cause actual results to differ materially fromthose in forward-looking statements include, but are not limited to: (i) the


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ability of Marina Biotech to obtain additional funding; (ii) the ability of MarinaBiotech to attract and/or maintain manufacturing, research, developmentand commercialization partners; (iii) the ability of Marina Biotech and/or apartner to successfully complete product research and development,including preclinical and clinical studies and commercialization; (iv) theability of Marina Biotech and/or a partner to obtain required governmentalapprovals; and (v) the ability of Marina Biotech and/or a partner to developand commercialize products that can compete favorably with those ofcompetitors. Additional factors that could cause actual results to differmaterially from those projected or suggested in any forward-lookingstatements are contained in Marina Biotech's most recent periodic reports onForm 10-K and Form 10-Q that are filed with the Securities and ExchangeCommission under MDRNA Inc. Marina Biotech assumes no obligation toupdate and supplement forward-looking statements because of subsequentevents.

Contacts:

Pete GarciaChief Financial Officer(425) [email protected]

Westwicke Partners (Investors):Stefan Loren, Ph.D.(443) [email protected] John Woolford(443) 213-

[email protected]

McKinney|Chicago (Media):Alan Zachary(312) 944-6784 316 or(708)[email protected]

SOURCE: Marina Biotech, Inc.

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FierceBiotech-FierceBiotech

THURSDAY, JULY 29, 2010

Marina Biotech Continues to DriveSector Consolidation, Acquires


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Novosoms Liposomal Delivery IP

Marina Biotech, formerly known as mdRNA, continues to snapup assets in the oligonucleotide therapeutics and diagnostics

space, this time acquiring the liposomal delivery IP from

Novosom, a privately held drug delivery company based in

Germany. This comes only a week after shareholders approved

mdRNAs merger with tkRNAi company Cequent

Pharmaceuticals to form Marina Biotech. It will be curious to see

whether Marinas strategy of challenging Alnylam's industry-leading position by taking advantage of the depressed market for

oligonucleotide therapeutics will succeed in luring Big Pharma

and pay off for shareholders. The investment this time: $5M in

newly issued stock.

Similar to Silence Therapeutics, Marina acts on the premise that

in order to capture those lucrative partnerships, being able to

provide a choice of delivery technologies, plus some claims inRNAi triggers, too, is key. This, of course, is in contrast to

Tekmiras so far quite successful strategy of doing one thing very

well, meaning clinically maturing and expanding the

applicability of its industry-leading SNALP delivery technology

and avoid some of the deal frenzy and dilution of effort.

By the looks of it, Novosom has to be considered one of the more

bona fide delivery companies. Similar to Tekmiras SNALP,

Novosoms SMARTICLES can change their surface electrical

charge and therefore reconcile (serum and storage) stability with

endosomal release functionality. Unlike SNALPs, however, these

liposomes also contain anionic lipids, in addition to cationic and


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neutral lipids, and do not employ PEG stabilizers. This stability

can be attributed to the negative charge of SMARTICLES at

phyisiologic pH which ought to avoid various interactions with

host factors and resulting toxicities often associated withpositively charged lipids. However, as the pH acidifies upon

endosomal uptake of these particles, they become positively

charged and competent for membrane disruption and

cytoplasmic release. For similar reasons, ionizable SNALPs as

practiced by Tekmira not only employ PEGylation, but are also

essentially uncharged at physiologic pH.

In terms of IP, from the looks of it,Novosom has assembled arespectable IP estate with various fairly broad patents granted

also in the important US market. This should provide Marina

with considerable options to leverage its other liposomal assets,

trp-cage targeting technology and amino acid-derived lipids, that

I have felt lacked robust patent protection when used in

liposomal formulations similar in composition to Tekmiras

SNALPs.

Theory and IP, of course, are only part of the equation. In terms

of actual data, the literature bears out the tolerability of these

liposomes. In terms ofin vivo knockdown efficacy, I havent

really seen much for liposomal delivery of siRNA in the peer-

reviewed literature. There was, however, a paper on the

liposomal delivery of a CD40 antisense oligo (under license from

ISIS) in a rodent inflammatory disease model and that supported

specific CD40 knockdown and disease amelioration while the

unformulated antisense oligo appeared to be inactive. In general,

based on the literature and also Novosoms website, their

technology seems to be in the late rodent stage and yet to be


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validated in larger mammals including non-human primates and

Man.

There should, however, be an open IND for the delivery of a

DNAi compound (no mis-spelling) by PRONAI which makes use

ofNovosoms technology. However, it appears that PRONAIs

funding situation may have delayed actual dosing.

Novosom also entered into at least 2 collaborations with RNAi

companies. One with (now defunct) DNA-directed RNAi

companyNucleonics for treating hepatitis viral infections, and

one with Boehringer-Ingelheim for the validation of drug targetsin the liver and lung. Again, becauseNovosom is a private

company I can only speculate whether the lipids used by

Nucleonics in their soon aborted phase I study stemmed from

the Novosom collaboration. Similarly, the status of the

Boehringer-Ingelheim collaboration is unclear to me. Who

knows, but maybe Boehringer-Ingelheim is actively looking for

(liposomal) delivery and triggers for the development of RN

AiTherapeutics, which raises another point: although the press

release did not specify this, but selling what looks like the entire

IP estate would appear to be tantamount to selling the entire

company, existing partnerships and programs included.

But back to the fundamental question: Consolidating into a one-

stop-shop, almost an anti-Alnylam, a la Marina and Silence

versus technological deep-dive a la Tekmira- which strategy willcreate more shareholder value? The next 3 months should

provide for some of the answers.


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Please let your voice be heard and vote on the right.

Posted by Dirk Haussecker at Thursday, July 29, 2010

Labels:Alnylam, Boehringer-Ingelheim, ISIS, liposomal delivery, Marina

Biotech, Novosom, Nucleonics, Smarticles, SNALP, Tekmira

9 comments:

Anonymous said...

Dirk,Thanks for the new blog entry re; Marina Biotech. That was

much more than I had expected. I will post a link to your blog over atyahoo. Hope you don't mind. Joe/Miami Beach

July 29, 2010 10:28 AM

Dirk Haussecker said...

Joe,That's fine. The reason though I did not respond to your

earlier inquiry is that in some cases such inquiries don't come from

retail investors or other generally interested people like you appear to

be one, but in disguise from those that write reports on RNAiTherapeutics companies that are then sold for good money to

'traders', often of the short/parasitic type. Especially with broad

questions it can be difficult to tell.

July 29, 2010 11:56 AM

Anonymous said...

Dirk,There is an saying, "You can learn more about a person

from what he asks, than from what he says."I found the questionyou posted on the survey, telling.Most recently, you appear to be

a strong proponent of the technologies and general investment

prospects of Alnylam and Tekmira; however, clearly you are debating

the value proposition of the one-stop-shop business model, also.I

am very curious, for companies that you categorize as one-stop-


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shops, which specfic companies would you rank #1 and #2 for

technology and investment prospects?Further, if I now asked you

to rank Alnylam, Tekmira and these two other companies - what

ranking order would you come up with.I know I am posing a

challenging question as I haven't provided specific definitions of

"good technology" or "good investment" prospects... and I know a

good investment for one person, might be a terrible choice for

another; however, consider the same investment thesis you have used

to arrive at the value proposition of Alnylam and Tekmira, and apply

to all four companies.Thank you in advance.

July 29, 2010 8:56 PM

Dirk Haussecker said...

I believe all 4 companies deserve a look here. Clearly, as most

readers here will know very well, my favorite company both

investment and technology-wise is Tekmira- and it has been like this

for the last 2 years. With the industry's most advanced delivery

technology, essentially allowing for knocking down genes at will in

the liver and increasingly also in other tissues and disease states,

Tekmira is in an excellent strategic position in most regards. If you

have read the papers and patents by Tekmira and their collaborators,

I don't know how one cannot be excited about the future of the

company and what it could do for human health. Couple this with one

of the most attractive financial gearing in the small biotech space, an

$80M market cap is very attractive to me. Alnylam at $15 is

clearly attractive, too, but probably with a more limited upside than

Tekmira near to midterm. Simple gravity. Although Alnylam also

practices SNALP quite extensively and is getting better and better at

target picking, the business model is more capital

intensive/aggressive than Tekmira's which is something that Alnylam

ought to look out for. The prospects for clear clinical knockdown

results from their TTR and PCS programs plus Novartis and maybe

another $100M+ deal should put the share price back on track.

Silence and Marina...probably worth wetting the feet at this


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point. I've personally been adding Silence Therapeutics over the last

couple of weeks because of progress on the IP front which should

increase their leverage in partnership negotiations and contentious

relationship with Alnylam. The lipoplex delivery data looks promising

although by far not as extensively validated as Tekmira's SNALP. So

before increasing my position, I will wait for more scientific

validation in the literature. The risk is clearly very high, but so should

be the upside. A $10M upfront deal should probably more than

double its share price (market cap only $20M with about a year of

cash runway). I think it is not totally out of the question. I treat it as

an attractive LEAP option, or a hedge on Alnylam because all these

companies are vying for collaborators.In the case of Marina, I'd

need some more time to digest the recent deal flurry, its impact on its

financials and scientific strategy.

July 30, 2010 8:26 AM

.

Dicerna Gets Glaxos SR One to Join InvestorSyndicateRyan McBride 10/21/10

[Corrected---10/22/10 at 6:25 am ET. See editor's note] Watertown, MA-based Dicerna Pharmaceuticalssaid this morning it has brought in $4

million from SR One, the venture capital arm of London-based drug giant

GlaxoSmithKline. The funding makes Glaxos SR One the latest big-nameinvestor to buy into Dicernas new approach to silencing disease-relatedgenes to treat cancer and other diseases.

SR Ones investment brings Dicernas Series B fundingwhich was

initially announced as a $25 million financing in Augustto $29 million.Dicerna has now raised a total of $50.4 million from a syndicate that

includes Abingworth Management, Domain Associates, Oxford BiosciencePartners, Skyline Ventures, and SR One.

Dicerna, founded in 2007, is a relatively new entrant in the field of RNAinterference (RNAi), which uses short pieces of RNA to knock down


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expression of disease genes. The firms molecules are slightly longer thanearlier RNAi drugs under development at companies such as Cambridge,MA-based Alnylam Pharmaceuticals (NASDAQ:ALNM). Dicerna, which is

focused on treating cancer, says that its RNAi drugs are more potent andoffer a greater duration of gene-silencing activity than previous RNAimolecules. This is because its drugs work at an early point in the gene-silencing pathway. [RNAi drugs are made with short pieces of RNA, not

DNA, as was initially reported in this story. We regret the error.]

Brian Gallagher, a partner at SR One, is joining Dicernas board as anobserver. He and Christoph Westphalthe former CEO of CambridgesSirtris Pharmaceuticals who became president of SR One this yearare

based in Boston. Westphal knows the RNAi field well; he co-founded andserved as the early CEO of Alnylam.

We are very excited about the broad potential for RNAi therapeutics to

treat diseases caused by a large number of gene targets that areconsidered undruggable with todays pharmacologic treatments,Gallagher stated in a press release.

Dicerna is working on advancing its first internal drug candidate into clinical

trials for cancer, but the firm isnt saying what type. Doug Fambrough, thefirms CEO, said yesterday at Xconomys Bostons War on Cancerforum in

Cambridge, that its lead candidate is being developed in partnership with

Japan-based drug maker Kyowa Hakko Kirin.

Ryan McBride is Xconomy's correspondent. You can reach him at

[email protected], or follow him on Twitter at

http://twitter.com/Ryan_McBride.

Dicerna Snags Deal With Japans Kyowa HakkoKirin to Develop RNAi Cancer TreatmentsLuke Timmerman 1/4/10

Dicerna Pharmaceuticals has found some deep pockets to support itsapproach to creating RNA interference drugs. The Watertown, MA-basedcompany is announcing today that it has formed an alliance with Japan-

based Kyowa Hakko Kirin.

Under the deal, Kyowa Hakko Kirin will get access to Dicernas proprietaryRNAi drug technology against one undisclosed target on cancer cells. In


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exchange, Dicerna will get $4 million in upfront cash, plus $120 million inmilestone payments for success in development and commercialization, aswell as royalties on future product sales. The partnership can be

broadened over time to include as many as 10 more drug targets forcancer and other diseases, each with the same financial terms. Dicernaalso has an option to co-promote and equally split the profits in the U.S. onthe initial cancer drug.

This is the first significant partnership for Dicerna, a company founded in

2007 on the idea that it had found a second doorway of RNAinterference. Like Cambridge, MA-based Alnylam Pharmaceuticals andothers, Dicerna is seeking to specifically silence disease-related genes.

One key difference is that Dicernas drugs are a little longer than so-calledsmall interfering RNA molecules, and they interact with an enzyme called

dicer thats involved at an earlier step in the RNAi process. Kyowa HakkoKirin has a long history of manufacturing and marketing biotech drugs inJapan, and it has its own internal teams devoted to RNAi research and

development.

They looked carefully at different siRNA opportunities for some time, andthey chose this one, says Dicerna CEO Jim Jenson. They are committed

to biotech, and they are a strong player in Japan.

Dicerna still has a lot to prove about its method, as none of its treatments

are yet in clinical trials. The partnership does provide cash that will enableDicerna to add a few new faces to its staff of 23 employees, Jenson says.

It also helps provide outside validation that should enable the company toraise a Series B venture round in 2010, which he expects will be worth

NEXT PAGE

Luke Timmerman is the National Biotech Editor of Xconomy, and theEditor of Xconomy Seattle. You can e-mail him [email protected], or follow him at twitter.com/ldtimmerman.

Dicerna Snags Deal With Japans Kyowa HakkoKirin to Develop RNAi Cancer TreatmentsLuke Timmerman 1/4/10

(Page 2 of 2)


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about $25 million, he says.

Dicerna is hopeful that its drugs will be more potent than other RNAitherapies, and that they will last longer in the body. If that can be proven, itcould translate into fewer injections for patients, lower manufacturing

costs, and higher profit margins.

But delivery is the major challenge in RNAi today, because mosttreatments given directly through injection get filtered out by the kidneys

before they can have the desired effect on the target. Lots of energy isbeing poured into new ways to deliver the RNAi drugs in the body, and thatis one important feature of the Kyowa Hakko Kirin collaboration with

Dicerna. The Japanese company has its own technology for usingliposomes to deliver the RNAi drugs. Dicerna is developing its own lipidnanoparticle delivery technology in house, Jenson says, although it istrying a variety of approaches, like using antibodies, peptides, small

molecules, orother ways of getting an RNAi drug where its supposed togo.

Dicerna doesnt envision itself becoming a research wing for Kyowa HakkoKirin. Rather, this partnership will lead to more alliances and help the small

company build up its own pipeline of wholly owned drug candidates,Jenson says. Already, he says the company has commitments from its

existing investorsOxford Bioscience Partners, Abingworth, and Skyline

Venturesto invest in a Series B venture round that just needs a newinvestor to join the syndicate.

That round of investment will go toward building up the Dicerna pipeline,

he says. While the Japanese partnership will focus in the beginning on anovel target for a cancer drug, Dicernas own program will concentrate

instead on a less-risky target that has been validated by other drugs,Jenson says. The strategy is that by silencing a validated target, theresless chance of an unexpected safety problem emerging, which could casta cloud over the whole RNAi field, he says.

Clinical successes in this field are badly needed, Jenson says.

Jenson wouldnt say which target Dicerna is going to pursue first, but hedid offer some clues. Dicernas ideal target will be measured by a validated

biomarker, he says, so the company will be able to take a biopsy frompatients and determine whether its RNAi drug is getting to where it is


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supposed to be in the body, and silencing the intended target. Ideally, thecompany wont have to wait very long for this sort of scientific validation.Dicerna has already been working on a clinical trial design, and expects to

bring that drug into human testing in 2011, Jenson says.


Dicerna, Archemix Team Up to Make Souped UpRNAi Combo DrugsLuke Timmerman 7/21/09

Dicerna Pharmaceuticals has set its sights on silencing problematic genesusing what it calls the second doorway of RNA interferenceanapproach to the burgeoning field that other RNAi companies arent

pursuing. But to get its drugs over the transom and where they need to goin the body, the Watertown, MA-based company will need a little help, andfor that it has turned to Cambridge, MA-basedArchemix.

The two firms have partnered up to develop combination treatments that

will merge Archemixs proprietary aptamer treatments with Dicernas

gene-silencing drugs. Both companies hope the alliance will yield drugsthat can preciselyand potentlyhome in on the molecular roots ofdisease. Specific financial terms of the deal arent being disclosed,although Dicerna and Archemix will split the early development costs, and

Dicerna has an option to get exclusive rights to take the new drugs throughdevelopment, leaving the usual milestone payments and product royaltiesto Archemix if the collaboration bears fruit.

The idea behind RNAi-based drug development is to create speciallyengineered RNA molecules that selectively turn off disease-causing genes.

Entrants to the field typically have to pay some sort of toll to Cambridge,MA-based Alnylam Pharmaceuticals (NASDAQ:ALNY), which has an

extensive RNAi IP estate, but Dicerna insists it has found a seconddoorway. Simply put, its designing drugs that are a little longer than so-called small interfering RNA molecules being developed by Alnylam and

othersand which are therefore not covered by Alnylams patents.Dicerna says its drugs may have the added advantage of being more


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potent that other RNAi-based treatments.

Importantly, these slightly longer RNAi drugs can be made with a handleon them that allows them to be welded together with other drugcompounds that could give them extra kick. NEXT PAGE

Dicerna, Archemix Team Up to Make Souped UpRNAi Combo DrugsLuke Timmerman 7/21/09

(Page 2 of 2)

In this case, they hope to combine the Dicerna molecules with Archemixs

aptamersshort synthetic molecules designed to bind very specificallyand tightly to certain protein targets.

This provides a double-punch with one molecule, says Jim Jenson,Dicernas CEO. This deal is important to Dicerna and to the RNAi field.This will change the game.

There isnt any proof yet such drugs will work in people, so thesetreatments have a long way to go and a lot of high hurdles to clear.

Dicerna is also hedging its bets with a number of partners who bringexpertise with antibody fragments and peptides, which also might be usedto soup up its RNAi drugs. Dicerna already has established a couple of

research collaborations (which it hasnt disclosed) over the past sixmonths, and has several more discussions underway that it hopes will

lead to a partnership with a Big Pharma company this year, Jenson says.

This is an area of great interest in the Big Pharma world, Jenson says.

Archemix, for its part, gets to align itself with a glamorous niche within

biotech and keep itself busy as an independent company, a little more thansix months afterit got dumped at the altarby Lexington, MA-basedNitroMed

, which was looking to merge. Two months ago,Archemix namedKenneth Bate, the former NitroMed CEO, as its new top executive. This is

the first significant R&D deal at Archemix since he came on board.

This collaboration showcases how our proprietary aptamer technologycan be used in conjunction with other therapeutic modalities and we lookforward to beginning this exciting work with Dicerna, Bate said in a


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statement.

Dicerna wasnt about to say when it will enter clinical trials with one ofthese new RNAi-aptamer drugs, although it is most interested intreatments for cancer and metabolic diseases like diabetes, Jenson says.

Dicerna, which closed the last bit of its $21.4 million Series A ventureround last Julyright before the economy tankedis still doing well withits cash balance, Jenson says. But even so, pushing new drugs throughdevelopment will take more money. Dicerna plans to start raising more

money before the end of this year, Jenson says.

Luke Timmerman is the National Biotech Editor of Xconomy, and the

Editor of Xconomy Seattle. You can e-mail him at

[email protected], or follow him at twitter.com/ldtimmerman.


9391062879..Mukeshfor TLCplatesref from manish.

Read more: Marina Biotech Acquires RNA Delivery Assets of Novosom AG -FierceBiotechhttp://www.fiercebiotech.com/press-releases/marina-biotech-acquires-rna-delivery-assets-novosom-ag-0#ixzz13fzTLgjtSubscribe: http://www.fiercebiotech.com/signup?sourceform=Viral-Tynt-FierceBiotech-FierceBiotech

NitroMed and Archemix to MergeRobert Buderi 11/18/08

Last month, when Lexington, MA-based biotech company NitroMed

announced it was selling off all the assets related to its only drug product,CEO Kenneth M. Bate said the company would concentrate on

combining, through one or more strategic transactions, with companiesthat have significant unrealized value or growth potential.

Apparently it didnt take long for Bate to find that partner: the publiclytraded NitroMed (NASDAQ:NTMD) today announced it plans to merge


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with Archemix, a private Cambridge biotech company exploring new ways

to treat cancer, inflammatory conditions, and other illnesses with shortpieces of RNA or DNA known as aptamers. Completion of the deal would

mean that Archemixwhich pulled a planned IPO when the market forsuch offerings went sour early this yearhad found an alternative path tothe public market.

Ryan took a look at Archemix last month, just a few days beforeNitroMeds asset sale announcement, when the company signed a

licensing and options deal with Eli Lilly (NYSE:LLY) that gave theIndianapolis-based drugmaker options to evaluate Archemixs technologyand gain exclusive licenses to aptamers for up to two disease targets.

Archemix itself has not yet received FDA approval for any of its treatments,but is focused initially on developing drugs to treat blood disorders.

Under the all-stock deal announced today, the merged company will retain

the Archemix name and will be based in Archemixs current offices, butNitroMeds Bate will become president and CEO. Archemix shareholderswill own about 70 percent of the new company, while NitroMeds

stockholder will hold 30 percent. The firm plans to apply to relist its sharesof the combined company on NASDAQ, under the symbol ARCH, the

symbol Archemix planned to use when it filed for an IPO worth up to $69million in July of 2007.

Assuming the previously announced sale of NitroMeds assets goesthrough, it is estimated that cash and cash equivalents for the combined

company will be approximately $50-60 million at closing, according to thestatement.

Bob is Xconomy's founder and editor in chief. You can e-mail him [email protected], call him at 617.500.5926, or follow him on Twitterathttp://twitter.com/bbuderi.

NitroMed Takes Buyout Offer from Deerfield,

Dumps Archemix at the AltarRyan McBride 1/27/09

NitroMed (NASDAQ:NTMD), the Lexington, MA-based drug developer thatstruggled to market a heart failure drug for African-Americans, says it has

agreed to be acquired for 80 cents per share in cash by investment firmDeerfield Management. This means NitroMed bailed out of previous


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agreements to sell BiDil to specialty drugmaker JHP Pharmaceuticals andto merge with Cambridge, MA-based biotech firm Archemix.

Archemix issued a separate statement confirming the terminated deal withNitroMed, and the associated fallout. Now that its planning to be

independent again, Archemix said CEO Errol De Souza, who negotiatedthe deal with NitroMed, is resigning from the top job and will remain on theboard of directors. Duncan Higgons, who was previously executive vicepresident of business operations, is replacing him as interim president and

CEO of Archemix. De Souza had planned to step down after the mergerwith NitroMed.

Deerfields buyout offer, which is subject to NitroMed shareholder approvaland other conditions, came last month after NitroMed announced theprevious month that it agreed to an all-stock merger with privately held

Archemix. The offer represents a 25 percent premium above NitroMeds

closing stock price yesterday of 64 cents. The Deerfield bid putsNitroMeds value at about $36.8 million.

In October, before Deerfield made its bid, NitroMed said it would sell allassets related to BiDil (isosorbide dinitrate/hydralazine hydrochloride), its

heart failure drug approved by the FDA for self-identified AfricanAmericans in 2005, for about $26 million. Now Deerfields acquisition of

NitroMed is expected to close in April.

Archemixs and JHPs breakup fees with NitroMed provide some degree ofa silver lining. As part of the firms agreements with NitroMed, Archemix isdue to get a $1.5 million termination fee from NitroMed and JHP is

expected to receive $900,000.

Archemix continues to land lucrative deals related to its drugs calledaptamers, which use short pieces of DNA or RNA to bind with disease-

related proteins. Last month Archemix received $27.5 million in upfrontmoney in a deal to develop aptamer treatments for London-based drug

giant GlaxoSmithKline. Two months before landing the GSK deal, formerArchemix CEO De Souza told me that his firm had enough cash to support

operations through the middle of 2010.

Also, Archemix says that it has just started mid-stage clinical trials of its

lead aptamer drug for treating a rare blood disorder known as thromboticmicroangiopathiesement.


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Ryan McBride is Xconomy's correspondent. You can reach him [email protected], or follow him on Twitter athttp://twitter.com/Ryan_McBride.

NitroMed to Get $2.6M in NO DealRyan McBride 4/23/09[[Updated: see editor's note below]]NitroMed, a Lexington, MA-based drug

development firm, says it has struck a deal with French biotech firm NicOx

to sell and license nitric oxide-based technology to NicOx. NicOx will payNitroMed an initial fee of $2.6 million, and NitroMed is eligible for future

payments of $5.2 million from NicOx based on certain terms. NitroMed(NASDAQ:NTMD), which makes heart failure drug isosorbidedinitrate/hydralazine hydrochloride (BiDil) for self-identified Black patients,

says that the initial fee from NicOx would be distributed to shareholders ifthe payment is received before NitroMed closes its merger with entitiesaffiliated with investment group Deerfield Management. The merger wasapproved at a stockholders meeting this week and is expected to close as

soon as practical. [[Editor's note: this story was updated with the amountof future payments NitroMed could receive in this licensing deal withNicOx.]]

Ryan McBride is Xconomy's correspondent. You can reach him [email protected], or follow him on Twitter athttp://twitter.com/Ryan_McBride.

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