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Yeast or Goats ???
What does this GycoFi announcement mean re. GTCB's technique??
The announcement says they have managed to create glycolization in a yeast strain. This is a great accomplishment for them because it allows them to produce the same level of peptide protien complexes available via mamalian cell culture. This does not mean they can create the complex tertiary structure of the type of proteins GTCB will be targeting. Proteins of the most complex three dimensional structure require enzymes, co-enzymes and co-factors eg. zinc, magesium etc for their final shape. These factors actually form chemical bonds with the amino acids to produce finger like projections or other shapes necessary for a functional protein. These factors are not present in yeast cultures. Why is this "equipment" available in the mammary gland? The answer is in most newborn mammals, including humans, the immune system is not well developed. Since the newborn has little immune response of its own. It is provided "passive immunity" via antibodies that it receives in the mothers milk. These antibodies which would be digested in the adult are absorbed intact in the newborn. They are produced by the mammary glands.
Back to AT111
The really interesting thing IMHO about this AT111 study is the effect on reperperfusion. This could translate to a whole new set of markets for Atryn both in the transplant field and possibly CVAs and AMIs.
This is great stuff Flo patents are key.
How about
" The Udder Whey "*
* N,B. Not a reference to how many times the stock has been churned.
The subject of ATIIIs anticoag properties is confusing because Heparin does greatly potentiate the effect ATIII on thrombin (about 1000x) But ATIII being a serine protease inhibitor and most of the cascade being serine proteases, Heparin is not necessary to inhibit factors IXa,Xa,XIa, or contact factor.
I'm not sure you are right about ATIII not posing a threat to coagulation in the absence of Heparin. I might be wrong but my understanding is ATII by itself blocks the coagulation cascade at several levels. Certainly in the JAMA article they mention the risk of hemorhagic complications from ATIII.
The combination of anticoagulant and anti inflamatory actions of ATIII raises some exciting possibilities. I am most intrigued by the potential (as yet not studied) for Atryn to limit cellular apoptosis after CVAs or AMIs. Recently I had a chance to raise these questions with an acquaintence working on neurological diseases. He said he would look into it (he was not familiar with ATIII). He has not got back to me yet.
Imho big pharma has no other choice but to "get on board"
I might be wrong but somewhere I heard the were doing the vaccine in mice????
Good news
I meant it did not seem to be important to Soros that the Russell Index had delisted GTCB earlier this year. Im sure you remember all the discussion on the Google board.
Guess George doesn't get the Russel report.
George Soros
A man of wisdom, judgement and experience; a Wall Street name,a player, one of the big boys has put a million dollar bet on GTCB. That's wonderful news. Those copycat fund managers will be chewing on this one.
market evaluation GTCB
The biggest mistake the market is making in evaluating GTCB is a failure to understand the importance of the company's intellectual property, ie. its patents.
String Theory in physics is a complex theory which attempts to explain the fundamental nature of the universe. String theory has been described as a late 21st century theory which fell into the 20th century. The problem is the mathematics involved in the theory is too complicated for anyone to solve at this time. The solutions await developments in math that will come in the future. Transgenics has some similarities. Transgenics provides a platform which will allow the production of what are at present hard to obtain complex proteins in quanities sufficent for clinical use. The problem is the scarcity of these moieties has pretty much excluded them from use in clinical medicine. Atryn is a good example. Everyone agrees on the HD indication, but AT3's indications in various acquired defficiencies is less clear. This is not Atryn's fault, Atryn may be useful in many conditions, it is a reflection of medicine at present. Clinicians have little motivation to study the effects of drugs that can not be obtained.
Transgenics can also be described in terms of state of current medicine as a method of producing drugs of enormous power and value which are not known to doctors at present. Like physics we must wait for the math. Transgenics will spur developments in medicine by putting these proteins in play.
In the end transgenics represents progress which will not be stopped. There is no clear alternative at present. GTCB controls the patents and they are true value.
This article was interesting. It's incredible how big the anticoagulant market is. Though I can't see how burns will fit into the Atryn story, I wonder now that AT3 will be more widely available if there might be some role for it in treating AMI and stroke. It doesn't seem much of stretch to think a drug which has anticoagulant and anti inflamatory properties might be useful in both conditions.
I think there is some confusion over what happens in burns.
The clinical condition would be a critical third degree burn involving over 30% surface area.
It is true the onset is acute, but the condition has to be considered a chronic one in which a series of acute problems arise. It is however the duration of the treatment period until skin coverage of the burns is accomplished that most effects survival. As mentioned previously burn patients who survive the initial stages ie. don't die of respiratory problems or fluid shifts, go into an extreme hybermetabolic state which persists until coverage is accomplished. It is very difficult to provide sufficient caloric replacement and negative nitrogen balance occurs. This causes protien wasting with muscle and organ loss and most importantly immune imcompetence. The great suseptabilty of these pts to bacterial infection combined to their lack of typical responses to infection eg. no temp rise or white cell response makes diagnosis of infecion an ongoing challenge. The clinical histories of these patients frequently include several episodes of sepsis survived followed by one they don't.
I am therefore uncertain as to how an Atrin trial might be designed.
Re Burns,
Burns as a clinical enity are complex. I offer the following as a Cliff Notes brief explanation of burns and their treatment. There will be a lot left out.
Burns are classified as chemical, electrical, or thermal. Since thermal are the most common and the other two are special cases, we will stick to thermal. Burns are also classified by depth of injury from 1st degree (superficial) to third degree in which the entire thickness of the skin is involved. The important distinction between first and second vs third is that third degree burns require coverage by skin grafting. We will stick to third degree burns (this doesnt mean 2nd degree cant be problematic). The severity of burns and survival rates depend on the percent surface area of skin involved. Excluding critical areas ie. hands, feet, genitalia, face usually burns over 30% would be considered critical.
Burns can be associated with respiratory injury (smoke or toxic inhalation) particularly when the burn occurs inside an inclosure. Wood smoke contains aldehydes (including formaldehyde) and fires in nightclubs may release toxic fumes and carbon monoxide which kill very quickly. The presence of signs inflation of the upper respiratory system is a bad prognostic indicator.
The initial problem severe burns present is in fluid and electrolite management this is related to inflamation and loss of skin coverage which normally slows evaportive water loss from the body. Infection is surprisingly unusal even in 90% burn before the fifth day. The usual regimen calls for lo dose Penicillin to prevent Strep infections which can come early
The real trouble with extensive body burns is that it takes longer to graft a 90% burn than it does a 30% burn. Burn pts must use areas of their bodies which have not been burned to graft the burned areas. If thin split thickness grafts are used, the donor areas may be re-harvested after three weeks. As you can see a patient with 90% burns can only graft from a 10% area so total grafting takes many reharvestings.
Burn patients go into a hypermetabolic state in which they have tremendous caloric requirements. They are similar to advanced cancer pts in that they enter a negative nitrogen balance. It is very hard to keep up with these demands. This altered metabolic state persists until the patient gets coverage. The most serious consequence of this is on the immune system. The combination of large areas of exposed flesh and an impaired immune is the real problem in extensive burn survival because of the suseptability to all kinds of micro organisms.
Thankyou,
Very infomative, subsetting makes alot of sense in this setting.
Yes,,,,, this is quite impressive.
Thank you very much. The Hoffmann et al paper was very helpful. Onward the DIC trials.
I have re-read it (the Warren paper) and can see there are just enough nooks and crannies in the conclusion to justify GTCB taking another try at it. I hope the EMEA's "guidence" means they feel the same. Am I wrong or did one of your posts say Leo was putting up the money at least thru phase 2 ??
Do you know if the company has any interest in re opening the aborted trials involving by-pass surgery?? It seemed to me the indication was good and the trouble was with the surgeons who wanted to continue using Heparin along with Atrin. Six years have passed they might be more receptive.
Dew, Could you please explain.
The AT3 study reported in JAMA (Warren et al) you refer to as the Kyber-Sept study concludes there was no improvement in the 28 day all cause mortality rate in the AT3 treated group over the placebo group. An editorial in the same issue on the role of AT3 states, "Does the study by Warren et al confirm that there is no role for antithrombinIII supplementation in sepsis? The answer is likely yes, at least for patients similar (ie with DIC) to those enrolled in this trial." The editors apparently did not think the Heparin effect was very significant. Is GTCB going to have to prove that Atrin without Heparin improves the 28 day survival???
If this is the case how can Cox (see the Jan 2006 interview) claim treatment of sepsis will be an important indication in the expanded aquired defecincy category. I dont have the charts and may be wrong but I'm almost certain at the stockholders meeting in Waltham he listed the sepsis market as very big for Atrin.
I've also heard burns mentioned as an indication. I have not recently, but in the past I worked clinically on burns, first as a general surgeon in RVN and later during plastic surgery residency in Gainesville Fla. I am currently in practice in the Boston area. Severe burns are extremely complicated clinical situations. It is unclear to me where AT3 might help.
I would appreciate any literature cites you could provide.
Question for Dew or anyone who knows the answers.
1. How firm is the evidence AT3 is of benefit in DIC.
My brief look at the clinical literature on the benefit of AT3 in DIC turned up one major study (Warren B.et al High Dose ATIII in Severe Sepsis, JAMA 2001:286: 1869-1878). This was a large 2314 pts random prospective double blind study. The conclusion was AT3 had no effect on the 28 day all cause mortality. Another study on guinea pigs suggested surpra pharmaceutical doses of AT3 were beneficial (all the gps survived).A later review suggests the reason for the poor showing in Warren's study (not mentioned by name) is the patients were additionally given Heparin. Heparin apparently inhibits some of the actions of AT3.
My concern. which hopefully is unfounded, is the company not pursue a wrong course.
2. In 2002 it was suggested AT3 might have a roll in prevention of angiogenesis. Anyone know any more??
That is a very interesting conjecture.........hmmm
I agree
He's definately from the "Mister we could use a man like Herbert Hoover again" school." Those radio tubes were plenty good enough for us."
Its pretty clear transgenics is the way to go. His type will simply fall behind and be lost.
Dear OKY.
I hope that wasn't too biospeaky. Actually all the hub bub over using goats reflects a poor knowledge of the history of medicine. An embarrasing number of medicines are derived from plants and animals.
Asprin...........from willow bark
morpine .........from poppies
digitalis........from the Foxglove plant
insulin..........from pigs
tetnus vacine....from horses
premarin.........from mares urine
These all all therapeutic agents ie medicines that effect systems. It s just they were all discovered more or less by accident without any real understanding of how they worked at a molecular level. In medicine this is sometimes called the peanut butter method. You start with a disease without a cure and you give it to a thousand monkeys. You then treat the monkeys with all kinds of things. If some of monkeys get better on peanut butter you start a whole bunch on peanut butter, if they get better you have discovered the cure.
We are entering a new era, a paradyme shift brought on by an exponential growth in our ability to understand biological processes on the molecular level. This has been triggered by electronic developments which aid the study and the manipulation of this micro world. The most important of which is the computer whose enormous power has resulted in feats like mapping the human genome.
ATIII is a regulator in the coagulation system. The coagulation system effects blood clotting. Clotting of blood is a complicated sequence of events requiring chemical reactions to produce products which then effect another reaction and so forth. The purpose of such a system is to allow clotting at an injury site, but not allow the clot to continue and involve the whole blood system. The final step in the process is the conversion of fibrinogen to fibrin, which is the clot. Thrombim is the agent which triggers this conversion. Anti Thrombim acts to stop the action of thrombin. If someone is defficient in antithrombin they will be more likely to have problems with blood clots
Dear OKY,
The principal problem with therapeutic proteins derived from blood plasma is the possibility they may be contaminated with infective particles such as HIV, Hepatitis, etc. Plasma products require donors (human) plus complex extraction processes, sometimes have limited shelf life, are heavily regulated, and frequently in short supply eg. ATIII.
Therapeutic protiens are complex organic molecules much too large to be produced in a chem lab, requiring DNA RNA for their specific sequencing. Some protiens, but not all can be produce by bacterial or mammalian cell cultures. This requires expensive manufacturing sites manned by expensive human workers. Transgensics requires less start up capital; (a bio fatory can require three years to build). Transgsgenics can produce a wider range of therapeutic proteins eg. monoclonal antibodies which are difficult to produce by other methods.
The trend in medicine at present is to develop regulatory molecules which control processes within systems ie nervous,
immune etc. The idea is disease processes result from poor or lack of regulation within the systems they effect. The regulators are complex protiens. Transgenics is the best method to produce these regulators at present
Dear Dew,
Please accept my apology. Didn't realize I was being snippy.
Dear OKY,
Good point. Always enjoy your posts. Inciteful and entertaining.
Dear Lancecraft,
I agree 100%.
Dear Dew,
I understand The EU was a rubber stamp, but I like Aslan am very happy to see the rubber stamp stamped. With GTCBs track record I'm sure a lot of long term followers were happy to see the company did not break the record by becoming "the first company to be denied the stamp."
Symbolism is important.
I would agree. I'm sure GTCB understands the true measure of its value is its proprietary intellectual property; ie its all about the patents.
I must confess to being amazed at the comatose reaction of the market to this monumental event anounced today. I guess it's a testamonial to the depth of the company's "fallen angel" status. It was not too long ago the stock was trading over two on anticipation of a posative opinion and was up to fifty dollars ps in 2000 when it was behind where it now sits..........oh my.
Hopefully these short sighted types collecting their 25cent profits will have a good story to tell their grandchildren. How they sold GTCB at $1.40, and how they all could have become rich.
We are fortunate.
For many years, GTCB could be compared to Brazil. Pregnant with potential, but seemingly abandoned by fortune. The company knows heartache and disappointment, not all of which is it's fault. The EMEA decision in Feb was merely the latest.
We have recently debated the wisdom of the latest dilution, but it is really only a side issue. Even though the market has not fully appreciated the importance of the the reversal of the EMEA's opinion, imagine how different things would be for GTBB now. Financial constraints would probabibly forced them to concentrate on the FDA approval. Now it appears they need more money to pursue that goal, imagine the difficulty of raising the capital. The company in all likelyhood would have not seen the OK of Atryn until 2008. As an added benefit, it seems likely with the EU approval GTCB will gain some currency with the FDA as they go through that process.
Somehow I had the incorrect idea they were going for Acquired def. approval. Hereditary is much easier and does not mean they will be restricted from the larger acquired market. The FDA is much more interested in regulating manufacturers than physicians. For example, Botox (Allergin) is FDA approved only for the glabellar area (Scowling), but it is used by physicians for all areas of the face, and more and more to control headaches and facial pain.
I think GTCB is finally having a little luck
Thanx for the reponse
I personally have met and talked with Geoff Cox and think he is very impressive. I am not committed to any position. What bothers me most is I have a number of questions and I can't seem to find the answers. If there are posters who can answer these questions with logic or facts it would be appreciated. I am not a trader and have held a position in this company since the nineties
(1) Why did GTCB choose this time and this method ie. sale of shares to raise money. Please, I understand they think they need money. My perception of the company is one making exciting progress both on a scientific and in the near future a financial level. Most businesses in this situation would probably have considered a loan. Genz. is flush at present and it seems likely could have provided a line of credit, 17.5 million is not an enourmous sum. Selling stock to raise money is a better tactic when you feel your stock is over priced.
(2) Is there a problem with Atrin revinues. I would like Cox to elaborate on why Leo will not be able to begin distribution
of Atrin until 2nd quarter 2007. I understand it has something to do with finalising agreements. If anyone knows about this please explain. Also is GTCB sticking with the 50 million a year for Europe.
(3) Is there trouble brewing with the FDA trials? I remember the unexpected difficulties in the 2000 trials which were also
based on aquired conditions. As a clinician I know the problem with aquired conditions such as DIC is they are usually unplanned. This requires convincing the involved physicians to use the new medicine in lieu of older methods with which they have greater familiarity and are more comfortable with. Maybe someone could elaborate.
Excuse me Your Majesty
I guess when anybody disagrees with your opinion it's venting.
I understand from the patriarchial tone of your editorials, you much prefer opinions which accord with your own.
Sorry, in the midst you editing my posts, and congradulating your subjects; youv'e missed my points. True I do not think the managements decision to do financing at this time or manner was wise. But if you read my vent, I admitted I had insufficent information, and if the management would disclose the reasons for this action I would be delighted to be proven wrong. I'm sorry, but you and Itchy are wrong. Whether management has a personal investment in the company or not does not free them from the obligation of disclosure.
This if a huge offering (not moneywise, but sharewise) Again you probably no more about the distribution, holding periods etc. but it is clear they have the potential of hanging over the stock for sometime.
Comments like sell your shares if you don't like it.. are arrogant.
Sell if you think the management performed poorly.
Urche,,, are you by any chance related to Marie Antoinette??
You seem to be from the "Let them eat cake" school. The problem is after management's "fresh air policy," the peasants have indeed taken a hike. The stock is down about 25% and I'm not too excited about taking that kind of loss on a very big position. It's all well and good to talk about short sellers, selling on the come, short selling against the box etc. but the truth is short selling is only effective when there is no real support for the stock. Since the science is good, a lot of this lack of support has to laid at the feet of management.
On a site like this the possibility of hidden agendas is real. From the information available I do not think this last financing was a good idea. The dilution will be perminent almost 30% the money short and soon gone. I would loved to be proved wrong by the company coming forth with more information, but I don't hold out much hope.
I have a lot of respect for all the work you do to help investors on this site understand the Bizanthiun world of GTCB. Generally your posts are enlightening and educational, but I must respectfully disagree with some of your points. I been a long term investor in GTCB and Tissue Repair before that. I have owned Gilead, Gern, Genz. and quite a few whose names I can't remember. I can not recall another situation quite like this. It's certainly true fledgling biotechs need money like vampires need blood, at least until the company develops a revenue source sufficient to pay its bills. What is unique about this situation is in all other cases the company was smart enough to wait until some 'stellar' news event or some form of prestidigination was preformed to get the share price up and not start a fire sale when the stock has the dwindles. I am fully aware to quote Gecko, "Management has no invesment in this company." They still have a responsibility to the share holders. Since the company is not in straights, and the EU announcenent is coming in a few weeks, why not wait?
You are on record as saying "no one is going to take this company private." I appreciate this is an honest opinion but I wonder if you can be sure. I hope your'e right
Many of you are waundering around blind without a cane.
I have been invested in this company since the nineties when it was Genzyme Transgenics. I have purchased most of my shares at considerably more than two dollars a share, and would be most unhappy to see the company "taken private" at two bucks. That would rep a market cap of 160 million for a company with a potential worth of many billions. Pardon me, but this deal has a peculiar odor. I do not care whether the company approached Harrison or vice versa,, the deal stinks. Sure we all could use a little cash from time to time but we don't sell our house for half price.
You of course are right I should have said EU and not EMEA. I appreciate your insights into Geoff Cox's presentations. I must have been napping during the uplifting parts. I apparently was not able present the important points of my post in a clear and concise manner. (A) I can not see any reason why this company should sell stock at this low price when; (1), they have sufficent capital to meet expenses for the next 6 months at very least, and (2), they have every reason to expect posative developments ie. approvals partnerships, in the oncoming months to increase the PPS and make dilution more palatable. (B) I am uncomfortable with the notion of allowing any individual our group to aquire close to a 25% interest in the company they did not have to purchase in the open market. (C) Publicly traded companies are required by statute to be reponsive to their shareholders. IMO GTCB owes us a better explanation of their actions than has been provided. As shareholders we should demand an explanation.
I am a long time shareholder in this company. As such I have suffered more long term disappointments than any Red Sox fan. I have never been one for conspiracies, but this latest dilution has me thinking. IMO there are few reasons why this company would offer such a large volume of stock at this price when the prospects look so good. If they need money why not wait for the EMEA approval a partnership announcement ect. to move the price up. The first reason might be they have learned the Europeans are coming with a negative opinion. This would push the date when the company could develop a self sustaining revenue stream into 2008. The European decision would make financing even more difficult. I realy do not believe this is the case. They would certainly have to disclose this to the underwriters, or face serious consequences.
It almost seems like theyr'e giving this stock away. Cox's presentation on July 12th bordered on being morbid. Timing is crucial for this company, as it is for all fledgling biotechs. Cox seem to be giving the worst case scenario on every possible coming event, "like a basher trying to get the stock down." And it went down. The effect of this dilution allows William Harrison to gain control of the company without having to buy that rite in the open market.
Mangement is accountable to shareholders. I urge everyone to write the company and insist on an explanation of this recent event.