| From: donpat | 3/25/2006 7:18:31 AM | | | | | | Bristol-Myers Squibb
From:
tinyurl.com
*******************************************************
CLASS OF 1980
Title : I am looking for startup capital for a spinoff drug delivery technology company
From : Anil Diwan
Message : Hi guys,
Here is a business oriented recap of TheraCour, a drug delivery technology I have been working on for the past 10 years. This is the first time I am looking for Angel Investor and VC funds. So far, I have driven the ventures solely on direct sales and income from business! Please help. You can email me at adiwan@iitbombay(.)org.
TheraCour Pharma will be a spinoff from AllExcel, Inc., West Haven, CT (near New Haven, Yale U) where the Specialty Drug Delivery Vehicles, trademarked TheraCour have been developed over the last 10 years, and are now ready for commercialization.
TheraCour is an advanced drug delivery technology that helps solve all three major challenges of drug delivery: Solubility, Permeability, and Targeting
TheraCour Pharma has a 3-Tier Revenue Model, with revenue generation starting as early as 2nd year, and net positive cash flow as early as 5th year. [Research Market Sales, Licensing Fees, and Commercial Royalties are the three tiers]. Research Market Sales do not have FDA registration needs.
Investment Needs:
Currently, we need about $2MM in the first year to solidify IP position and solidify some of the nascent PharmaCo partnerships.
A total investment outlay of $25MM will be needed to reach the planned controlled growth with a highly conservative estimated net income of about $25MM p.a. in Year 6, which will double in Year 7, and grow at 20-30% p.a. for another 3 years to a stable plateau. There is opportunity to use the income to develop our own drugs and take the company to multibillion dollar valuation.
An ambitious growth plan that reaches net positive cash flow in 4th year and at higher revenues is possible with a investment of about $40MM.
Clear Milestones that are achievable and can be traced for investment inflows have been developed.
Product Positioning:
The specialty drug delivery marketplace addressed by TheraCour is worth about $10 billion (injectable excipients, liposome technologies, and airway delivery). There are only a handful of players (only 5 significant players) in there, and we have technological edge over all existing players, as well as potential in-comers. The most successful business, Alza, based on liposome technologies, had sales of leading drug Doxil at about $1billion, and was purchased by J&J for $10billion. This is the potential we can reach and probably even go beyond, in ten years.
Barriers for Competition: Our entry into the market will be a great barrier for new companies to surpass since
1. we solve all three major drug delivery challenges, and since
2. commercial usages requires developing expensive FDA registered ToxPackage data and Drug Master Files.
3. We have significant cost and performance advantages over liposome technologies.
IP Proprietary, Patentable, Leading Edge Technologies
The new TheraCour technologies to be commercialized are currently fully proprietary and have international patentability. We have one patent issued on our older technologies, indicative of our leadership position.
Market Need is Addressed
We already have interest from several Pharmaceutical Companies in TheraCour technologies. We are in the process of reaching a Material transfer Agreement with Bristol-Myers-Squibb shortly, for BMS to evaluate TheraCour drug delivery vehicles in a solubility pre-pilot. Our corresponding internal pre-pilot is successful.
Choice of a drug delivery vehicle by a PharmaCo is based purely on performance and cost metrics. We have an edge in both of these (technical details need to be discussed here).
We have a strong Management Team, consisting of Board Members Mr. Harry H. Penner , Jr. (seasoned PharmaCo executive and dignitary, Legal Counsel), Dr. Vivek S. Kavadi (Oncologist, Chair, Cancer Srevices Center of US Oncology; Harvard MD, Rice BA), Mr. Rana Tewari (International Finance Expert), and CEO Anil R. Diwan ( inventor of TheraCour and several other technologies, successfully managed two businesses and navigated through tough times with an eye on thrift, cost consciousness, high productivity metrics and balanced books; Rice Ph.D., IITBombay B.Tech.), COO/Business Development Mr. Joe Kaufman (formerly VP, Informatics at Agilix, Inc., inventor of two Agilix patents), CTO Jayant Tatake (experienced in GMP Production of Pharmaceutical Intermediates, Synthesis and Process Scaleup, UDCT Bombay PhD). All of our exceutives and management team members have 15 to 26 years of experience in the specialty pharmaceuticals related businesses.
We are now preparing scaled presentations for different audiences and with extensive visual impact. We are also refining the story-telling.
Nitin D, Ram K: This is the great thing I had said I was working on in the few years ago's note.
Please review the Terms of Usage provided on the disclaimer page prior to accessing this website.
ACCESSING THIS WEBSITE SIGNIFIES YOUR AGREEMENT TO THE TERMS OF USAGE.
Home | What's New | Contact Us | News | Directory | Alumni | Class Notes | Y-Point | Jobs | Messages | Search
Copyright © 1996-2005 IIT Bombay Heritage Fund, Cupertino, CA, USA
**************************************************** |
| | NNVC - NanoViricides, Inc. | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last Read |
|
| From: donpat | 3/26/2006 8:24:41 AM | | | | | | Pig virus hits Ontario herds
Sun, March 26, 2006
By CP
STRATFORD, Ont. -- A virulent new strain of a common pig virus is wreaking havoc on Ontario hog herds.
Tens of thousands of hogs have been removed from farms by deadstock companies this winter and last year.
They are victims of new strain of porcine circovirus or other illnesses that the autoimmune disease brings on or makes worse.
"It's just terrible the number of animals that are dying from disease this year," said Winnie Linton, who has lost about half of the 2,000 hogs on the farm she and husband Dave run near Mitchell.
"We see the light at the end of the tunnel because our barn is almost empty," she added, managing a weak laugh.
Larry Skinner, chair of Ontario Pork's board, said provincewide mortality rates are running at 10% to 12%, or some five to six times above the norm on affected farms.
On the hardest-hit farms, the figure is 40% to 50% or more and he sympathized with those struggling farmers.
Meat packers are also starting to worry about a pork shortage, he said.
But for hog farmers, it's a double or even triple-whammy.
They're running up costs trying to treat the sick animals, losing revenue when the hogs die and don't make it to market, and feeling the emotional stress of seeing their animals suffer.
And all at the same time as they face market prices of 20 to 30 cents below the break-even mark of roughly $1.50 per kilogram.
edmontonsun.com |
| | NNVC - NanoViricides, Inc. | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last Read |
|
| From: donpat | 3/26/2006 8:35:57 AM | | | | | | Experts hope 1918 virus sheds light on pandemics
By Sandy Kleffman
Knight Ridder Newspapers
Sunday, March 26, 2006
WALNUT CREEK, Calif. — Terrence Tumpey stepped into the laboratory and glanced at the dead mice. Suddenly it hit him — the significance of what scientists were attempting.
A few days earlier, Tumpey had infected the mice with genes from the 1918 influenza virus. The virus killed 40 million to 50 million people in the worst infectious disease outbreak in recorded history, then vanished.
[CONT.]
deseretnews.com |
| | NNVC - NanoViricides, Inc. | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last ReadRead Replies (1) |
|
| From: donpat | 3/26/2006 8:45:34 AM | | | | | | When a Disease Loses Its Most Potent Ally, Fear
Jean-Christophe Kahn/Reuters
STORM BEFORE THE CALM A quarantined medical worker wears a protective mask against SARS in Beijing in 2004, and mad cow testing in western France in 2000. Both diseases are now seen as less of a threat.
By DONALD G. McNEIL Jr.
Published: March 26, 2006
THE obituary for mad cow disease was written earlier this month. Maybe you didn't notice.
The disease isn't really dead. But its power to terrify seems to be.
On March 13, the government said that a cow in Alabama was the third in the country to have the disease. The New York Times ran its article on Page 25, and other papers did roughly the same.
There was no clamor of "press cover-up!" But neither had the disease, formally called spongiform encephalopathy, which turns the brain into a grainy lump of Swiss cheese, become any less horrific since the first mad cow in the United States, discovered in December 2003, led to nervous "Is Beef Safe?" headlines across the country.
Instead, it had finally become clear that any threat to people is very, very remote.
Over the last two years, bending to pressure from consumer groups and its own inspector general, the Agriculture Department had finally tested 650,000 animals instead of a token handful. It had also adopted rapid tests and banned "downer" cattle from the food supply so that the most disgusting aspect of the first case would not be repeated: that the old dairy cow that tested positive had been in a truckload of animals so broken by age, disease and injury that some had to be winched out to the slaughter, and that all had been ground into hamburger and sold before the test results were in.
Mad cow isn't the only disease in recent years to soar into high-flying panic and then collapse into the "I wonder whatever happened to ... ?" category.
One could argue that the obituary for resurgent smallpox was written on June 18, 2003, and that SARS died on Feb. 19, 2005.
The first date is the one on which the Centers for Disease Control admitted that the smallpox vaccination drive ordered by the Bush administration in the lead-up to invading Iraq had ground to a halt. The administration had wanted 500,000 health workers to be vaccinated because Saddam Hussein or others might unleash weaponized smallpox. But barely 38,000 volunteered.
The latter date is the one on which a microbiologist from the University of Colorado, after a review of worldwide scientific literature, announced that the virus that causes SARS, a respiratory illness that had killed about 10 percent of 8,000 victims two years earlier, was no longer found in humans. (Later, scientists found that it thrives in bats, ending hope of total eradication.)
Why, in each of these cases, was a public frenzy whipped up, only to fade again? And what does that say about today's mounting frenzy over avian flu? In the past, "we cried wolf too fast, revving up the emotions and there was nothing to show for it," said Judith Walzer Leavitt, professor of medical history at the University of Wisconsin.
An obvious scapegoat is the media, which is often accused of being alarmist about medical news. But a more important factor was simpler: fear waxed or waned according to whether the public thought government was being honest.
In the case of mad cow disease, there were early accusations that the government was playing down the threat to protect the beef industry. The secretary of agriculture when the first case was found, Ann M. Veneman, was a former food industry lobbyist, her critics noted, and her chief spokeswoman's last job had been press representative for the National Cattlemen's Beef Association.
In the case of smallpox, there was suspicion that the government was exaggerating the threat to whip up support for its drive to war. As skeptics then pointed out, smallpox had been eradicated worldwide in 1977, and if Mr. Hussein had a cache, he presumably would have vaccinated his troops against it, which he had not.
In the case of SARS, it was not the American government, but the Chinese one, whose motives were questioned. It was concealing cases and refusing entry to international disease detectives.
"If you want the public's cooperation, honesty and frankness is much better," Professor Leavitt said.
In 1894, she noted, smallpox sparked a month of rioting in Milwaukee. The cause wasn't the disease itself, but the city's policy of seizing sick children in immigrant Polish and German neighborhoods and taking them to isolation hospitals, while leaving wealthy families alone, saying their larger houses and abundant servants would isolate them. With rioters flinging hot water and pepper in the eyes of the police and their horses, a vaccination drive collapsed and the epidemic spread.
Now the public is nervous about another potential pandemic.
Virologists disagree about whether the A(H5N1) virus that is killing chickens by the millions has the genetic power to do the same to humans, as the flus of 1918, 1957 and 1968 did. It could be a plague of medieval proportions — or it could fade as the swine flu threat of 1976 did.
Right now, the situation is reminiscent of SARS. Like that disease, avian flu originated in China, and some crucial questions have never been answered — like how much Chinese poultry vaccines were to blame for the disease festering in birds for nine years, and whether the virus infected thousands of Chinese who never got sick.
But no one is speculating about an American government cover-up. Its most respected health officials, like Dr. Anthony Fauci and Dr. Julie Gerberding, have admitted that the country is utterly vulnerable.
Nor is any powerful industry, like drugmakers or poultry raisers, accused of having a thumb on the scale of public policy, as the beef industry was during mad cow.
Predicting what a virus will do is impossible. But humans are predictable. John M. Barry, author of "The Great Influenza," a history of the 1918 pandemic argued that even if A(H5N1) becomes a killer, the panic it creates will fade faster than might be expected now, when a sense of mystery still enshrouds a threat that normally would sound silly — a "killer bird flu."
"What people are afraid of is the unknown," he said. "Not eating meat because you're worried about mad cow is like not going in the water because you saw 'Jaws.' But once the threat arrives, even if there's an undercurrent of terror in the whole society, people see the consequences and they get accustomed to it, just as they got accustomed to plague in the Middle Ages."
nytimes.com |
| | NNVC - NanoViricides, Inc. | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last Read |
|
| From: donpat | 3/26/2006 4:59:17 PM | | | | | | “Custom” Nanoparticles Could Improve Cancer Diagnosis and Treatment
Source: American Chemical Society (ACS)
Released: Tue 21-Mar-2006, 18:10 ET
Embargo expired: Sun 26-Mar-2006, 11:30 ET
Keywords
CHEMISTRY/PHYSICS/MATERIALS SCIENCES; MEDICINE/HEALTH; CANCER; NANOTECHNOLOGY/MICROMACHINES; CELL BIOLOGY; PHARMACEUTICAL SCIENCE.
Researchers have developed “custom” nanoparticles that show promise of providing a more targeted and effective delivery of anticancer drugs than conventional medications or any of the earlier attempts to fight cancer with nanoparticles. The nanoparticles also have the potential to reduce side effects associated with chemotherapy.
Newswise — Researchers have developed “custom” nanoparticles that show promise of providing a more targeted and effective delivery of anticancer drugs than conventional medications or any of the earlier attempts to fight cancer with nanoparticles. Designed at the molecular level to attack specific types of cancer without affecting healthy cells, the nanoparticles also have the potential to reduce side effects associated with chemotherapy, the researchers say. Their study was described today at the 231st national meeting of the American Chemical Society, the world’s largest scientific society.
The particles, considered the next generation of cancer therapeutics, are the most uniform, shape-specific drug delivery particles developed to date, according to researchers at the University of North Carolina (UNC) in Chapel Hill. Other potential benefits of the tiny uniform particles include enhanced imaging of cancer cells for improved diagnosis and use as delivery vehicles for gene therapy agents, they say.
To date, the UNC researchers have produced a variety of custom nanoparticles from biocompatible organic materials using techniques they adapted from processes used by the electronics industry to make transistors. In cell studies, they have shown that the uniform nanoparticles can attach to specific cell targets, release important chemotherapy drugs inside cells, and hold MRI contrast agents. Animal studies began recently and human studies are anticipated, the researchers say.
“I think this will transform the way one detects and treats disease,” says study leader Joseph DeSimone, Ph.D., a chemistry professor at UNC and director of the school’s Institute for Advanced Materials, Nanoscience and Technology. He has co-founded a company, Liquidia Technologies, to develop and produce the nanoparticles.
Researchers have been experimenting with nanoparticles as drug delivery vehicles for years but have had only limited success in cell and animal studies, DeSimone says. Each carrier has drawbacks with regard to stability in the bloodstream or ability to be directed toward a specific cancer site. In addition, there has been no general method available that allows precise control of the particle’s size, shape and composition, which are considered key features for the success of targeted drug delivery, he says.
Now, DeSimone and his associates at UNC have developed a new fabrication technique that allows, for the first time, unprecedented control over the structure and function of drug delivery nanoparticles. Called PRINT (Particle Replication In Non-wetting Templates), the technique is similar to injection molding and uses principles borrowed from the electronics industry for transistor fabrication, they say. The technique was first detailed last June in the online version of the Journal of the American Chemical Society.
The manufacturing process starts with a silicon wafer that is etched with the shape and size of the desired nanoparticle, resulting in a template. Next, nonstick liquid fluoropolymers are poured into the template and cured to form a fixed mold. The finished mold is then injected with organic materials that can contain imaging agents, anticancer drugs, DNA (for gene therapy) and other materials, depending on the intended function, DeSimone says. The new manufacturing technique uses gentler processing methods that are less likely to harm important organic components than traditional nanoparticle manufacturing techniques, he adds.
The resulting nanoparticles can be as small as 20 nanometers, or thousands of times smaller than the width of a single human hair. The shapes of the particles can also be made to mimic the shapes of objects found in nature like red blood cells or virus particles, DeSimone says.
Funding for the current study is provided by the National Science Foundation and the National Institutes of Health.
The American Chemical Society — the world’s largest scientific society — is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
The paper on this research, COLL 9, will be presented at 11:35 a.m., Sunday, March 26, OMNI at CNN Center, International Ballroom E, during the symposium “Biomolecular and Polymeric Nanostructures and Interfaces: Fabrication, Characterization, Function, and Applications.”
Joseph M DeSimone, Ph.D., is the William R. Kenan, Jr., Distinguished Professor of Chemistry and Chemical Engineering at the University of North Carolina, Chapel Hill.
© 2006 Newswise. All Rights Reserved.
newswise.com
Refs:
Liquidia Technologies
liquidia.com
United States Patent Application 20020168509
Kind Code A1
DeSimone, Joseph M. ; et al. November 14, 2002
Nano-and micro-cellular foamed thin-walled material, and processes and apparatuses for making the same
Abstract
Polymeric materials having a plurality of cells formed therein are described. The polymeric materials include a foamed layer comprising a plurality of uniform microcells, nanocells or combinations thereof in a closed cell network, a transition layer positioned adjacent to the foamed layer, and at least one unfoamed outer layer positioned adjacent to the transition layer. The foamed layer may be present in a volume ranging from about 80 to about 99 percent based on the volume of the polymeric material, the transition layer may present in a volume ranging from about 0 to about 10 percent based on the volume of the polymeric material, and the at least one outer layer may be present in a volume ranging from about 0.01 to about 10 percent based on the volume of the polymeric material. Methods of making such polymeric materials are also described, as are apparatus for providing foamed polymeric materials.
appft1.uspto.gov |
| | NNVC - NanoViricides, Inc. | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last ReadRead Replies (1) |
|
| To: donpat who wrote (1180) | 3/26/2006 5:01:51 PM | | From: MJ | | | | donpat
Read with interest the article reg. the 1918 flu. We lost two Great Grandparents in New York City-----they were young with a young baby who ended up being our Grandmother.
I have often wondered if the virus could still exist on effects of the family----i.e. old papers,passports, books----a wedding guest book, baby cards etc., deeds etc.------even old eyeglasses and appointment books.
All of the things----we love to collect and preserve.
If it can survive on these itmes, would seem that there is a chance of it being present in the environment without regard to the mice experiment.
Making another leap here----if the virus still exists on the old items, then is it possible this would help in the research such as being done with isolating the parts of the virus.
Any thoughts on this?
mj |
| | NNVC - NanoViricides, Inc. | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last ReadRead Replies (1) |
|
| To: MJ who wrote (1183) | 3/26/2006 5:17:33 PM | | From: donpat | | | | Don't think so - those researchers had to find the virus preserved in tissues of those buried in permafrost. So, unless those memorabilia have been stored in a freezer - not likely - I think the air, light and time in normal storage would have rendered any virus particles safe, IOW - dead.
Freezing stuff, living stuff, like foods and tissues and other living cells seems to preserve them indefinitely. While heat and normal everyday conditions does the exact opposite. I don't know why just that it does. |
| | NNVC - NanoViricides, Inc. | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last ReadRead Replies (1) |
|
| To: donpat who wrote (1184) | 3/26/2006 9:48:25 PM | | From: Solid | | | | Generally good reply about most viruses. They are a portion of RNA [half of the DNA molecule] and have the ability to inject themselves into cells and in effect force the cell to then replicate more viruses in place of normal cellular activity. They tend to exist in hosts or for relatively short time frames outside of hosts and some are more persistent then others. That is why colds can be spread with contact on mucus membranes often through touch but even with someone sneezing on you and tiny particulate matter from the ejecta lodging on your eye or sinus membrane, etc. HIV is tougher to spread and needs to be in body fluid and then transferred to another’s body fluid. Can't get it from the proverbial door knob. Usually blood to blood. That is why once a virus like smallpox is eradicated it may actually be gone from the world stage unless intentionally preserved in cold storage as you stated which is exactly what was done, and how Saddam came by via our intermediaries in '84.
A more interesting and quite dangerous and persistent pathogen is the spongiform for mad cow disease, a prion. One of the most simple and tenacious life forms on our planet. That puppy can exist in the most harsh environments for up to 10,000 years and be unaffected by its lodging awaiting opportunity to enter an available life form and weave its spell. That is why cooking, even well done and drinking strong alcohol with meals or even soaking the meat in it before hand basically has no effect on the prion, nor does sun or wind or rain. One resilient MF'er. Be grateful they are not on the memorabilia from 1918/19's viral outbreak.
Good job of listing some interesting articles and the need for companies to research cures and controls.
Virus may represent the single most dangerous threat and challenge to life on Earth, though as with all life forms ultimately it too is a part of our evolutionary balancing act. Pox virus is one of the most common around and basically has served to be a governor on over population for birds and animals and perhaps insects as well, not sure there. Smallpox is simply a specific virus that affects humans and generally needs a large high density population to take hold, hence the reason for massive outbreaks in urban regions. Spreads easily and takes off quickly with high density populations... Hence over population facilitates natural virus mutations to take hold when they mutate in a way that is beneficial to the virus gaining access to a new population of hosts. These occur all the time as adaptation to their environment. A large dense population of any creature susceptible to a virus potentially allows the virus to take hold more readily then very sparse populations that literally don’t lend a bridge to other hosts and hence can/do die out when other susceptible hosts are not around.
I hope that helps the poster with the old stuff. Not a problem at all. An aside. Those surgical masks that some old photos showed from the 1918/19 outbreak did absolutely nothing. They were like putting a huge fish net over your face, way to porous to stop the tiny virus. But is may have stimulated the immune system with the positive belief that you were doing something very helpful, the placebo effect. |
| | NNVC - NanoViricides, Inc. | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last ReadRead Replies (1) |
|
| To: Solid who wrote (1185) | 3/27/2006 1:19:15 AM | | From: MJ | | | | Yes, helps with understaning. Thanks.
What I would like to see is the development of meds/drugs for cancer that protect the healthy cells as noted in previous message here.
Have a friend just diagnosed with lung cancer after surgery and biopsy-----doctors giving mixed opinions-----this is the same as Dana Reeves had. One doc wants to treat with a med that is in trials that protects the healthy cells and then boost with chemo periodically to target the cancerous cells. Another wants to be agressive with the heavy duty chemo.
Having seen a lot of friends of all ages go through various cancers without success, can see the need for something other than chemo.
Pretty heavy stuff to consider.
mj |
| | NNVC - NanoViricides, Inc. | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last Read |
|
| From: donpat | 3/27/2006 4:15:49 PM | | | | | | RNAi works in monkeys
Apparent absence of toxicity and persistence of silencing may bode well for humans
[Published 27th March 2006 05:52 PM GMT]
A disease-causing gene was silenced in monkeys through RNA interference (RNAi) therapy delivered into the bloodstream, scientists reported online yesterday (March 26) in Nature. This is the first study to show that systemic administration of RNAi works in non-human primates, and the findings affirm the promise of this new type of therapy, scientists say.
In the study, gene silencing using the highest dose persisted for 11 days, without any observed toxicity, a finding that "bodes well for future human systemic trials of RNAi therapies," John Rossi of the Beckman Research Institute of the City of Hope in Duarte, Calif., who did not participate in this study, told The Scientist.
Scientists at Alnylam Pharmaceuticals and Protiva Biotherapeutics gave cynomolgus monkeys a single injection of small interfering RNAs (siRNAs) against the gene for apolipoprotein B (ApoB). This gene is involved in the assembly and secretion of low-density lipoprotein (LDL), and has not proven accessible to targeting with conventional small molecule or protein therapies. The researchers encapsulated the siRNAs in a liposomal formulation designed to target the liver, and modified their backbones to prevent siRNA degradation.
Gene silencing occurred in a dose-dependent manner. Within 48 hours, the maximum level of APOB silencing exceeded 90%, with a more than 75% reduction in plasma ApoB and a more than 80% drop in LDL. The researchers detected no reductions with empty liposomes or those containing mismatched siRNA.
Using 5' rapid amplification of cDNA ends (RACE) analysis, the scientists confirmed that silencing occurred via APOB mRNA cleavage at precisely the predicted site. APOB mRNA levels were substantially reduced for at least 11 days -- a silencing effect far more persistent than results previously obtained with rodents, which suggested APOB mRNA levels would recover within four to seven days. Alnylam president and chief executive officer John Maraganore said that metabolic differences between rodents and primates may explain why silencing persisted longer in this study.
The researchers saw no evidence of toxicity, such as pro-inflammatory cytokine production, a finding Maraganore attributed to in vitro toxicity screening beforehand and to the siRNA backbone modifications. The only detected change was a fleeting increase in liver enzymes in monkeys that received the high dose of the liposome-encased anti-APOB siRNAs, which peaked 48 hours after treatment and varied highly across individual animals. These effects normalized by the sixth day, and did not interfere with biological efficacy.
The researchers ended their study after 11 days because "the durability of the silencing far exceeded what we expected," Maraganore told The Scientist. They plan to continue longer-term experiments in primates, and improve the liposome formulations. Still, Maraganore said he believes they are ready for human clinical trials within the next 18 to 24 months.
However, scientists cautioned many details of the therapy should be investigated further. "The data is all from a single dosing, and it is going to be important to determine what happens after multiple dosing, as will be required for chronic liver problems," Rossi cautioned. While the liposome vectors the researchers used are most effective in delivery to the liver, they could also investigate whether the liposomes can deliver siRNAs to different targets, such as the kidneys or lungs, Rossi added.
Investigations should also tease apart how necessary the backbone modifications are to the therapy's effectiveness, Martin Woodle at RNAi therapeutic company Intradigm in Rockville, Md., who did not participate in this study, told The Scientist. "Nanoparticle and liposomal systems are now quite well accepted and very successful, without invoking the need for chemical modifications of the siRNAs themselves," he said. Future research should also investigate whether systemic delivery localizes siRNAs selectively to the liver, or if the silencer reaches other organs, as well, Woodle added.
Charles Choi
cchoi@the-scientist.com
Links within this article
T.S. Zimmermann et al. "RNAi-mediated gene silencing in non-human primates." Nature, published online March 26, 2006.
nature.com
C. Choi, "Mice tolerate siRNAs," The Scientist, November 24, 2004.
the-scientist.com
A. Adams. "RNA therapeutics enter clinical trials." The Scientist, January 17, 2005.
the-scientist.com
Alnylam Pharmaceuticals
alnylam.com
[[The central dogma of biology is that DNA makes RNA which in turn, makes protein. The abnormal production of proteins is the cause of most human disease. Today's drugs act by blocking the action of disease-causing proteins. RNAi creates the opportunity to silence the production of disease-causing proteins and therefore, represents a whole new approach for innovative medicines.]]
Protiva Biotherapeutics
protivabio.com
[[Protiva Biotherapeutics is a development stage biotechnology company, focused on pharmaceutical products to fight against cancer, metabolic and infectious disease. Protiva's technology, employing lipid nanoparticles to encapsulate and deliver nucleic acid based drugs, such as siRNA, allows for the development of molecular therapeutics that act selectively at sites of disease.]]
J.F. Wilson. "The biological basis for atherosclerosis." The Scientist, October 30, 2000.
the-scientist.com
J. Soutschek et al. "Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs." Nature 432, 173-178, November 11, 2004.
nature.com
John Maraganore
alnylam.com
Martin Woodle
intradigm.com
the-scientist.com |
| | NNVC - NanoViricides, Inc. | Stock Discussion ForumsShare | RecommendKeepReplyMark as Last Read |
|
| |
