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Up 9% in after hours trading.
I do find it interesting that a lot RPRX holders are JAV holders as well.
Bought more. I sold all of my IBB and loaded up on RPRX. Christmas in August.
At this price, I would like to buy more to lower my cost basis, however this stock already represents 27% of my portfolio. Hmmm... its going to be a tough call.
yep, this is a stock that nearly touched 20 in january.
I wonder how much money you could make buying this stock every time it touches 99 cents and then selling it at 1.02.
Plasma-derived antithrombin is already approved for DIC/sepsis in Japan and some European countries, but I guess that’s a detail that wasn’t consistent with your message.
And I would refer you to the Kybersept study which showed that AT3 failed in its clinical trial and showed an additional risk of hemorrhage. Please stop now. I dont feel like getting into a dragged out debate about sepsis. Thanks, Dew.
AMGN... word on the street... is that they're going to start sampling Enbrel, which is forcing Abbott to start sampling Humira.
So let me get this straight, at the same time AMGN is firing 2600 scientists, its going to start giving away its multi-thousand dollar per dose TNF blocker for free. Brilliant.
The short interest for GTCB is 0.56% of the float. That is infinitesimally small for a biotech. Basically there is no short interest driving the price of this stock.
Question about AMGN layoffs...
Anyone have specific details about who goes and which site? Thanks in advance.
PC
So lets recap. You are warning about problems with purifying proteins from milk. I then brought up that there are also problems from CHO cells. I bought up CHO cells because that is a production system of wide usage right now. You responded by trying to raise fears (unrealistic in my book) about herd contaminations. I responded that the goats are in a very controlled environment and that you have greater risks from public contact from humans in closed spaces. Where are you going to get your proteins from?
I am trying to figure out what your problem is, assuming you are not simply a fear mongering short. I also stated that compared to purifying proteins (including rATIII) from pooled human blood, GTCB's approach is far superior and safer. Do you disagree and think that it is safer to purify from blood? Here are the choices, ATIII from pooled human blood or purified from goats milk.
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What's there to recap? You originally made a completely unsubstantiated claim that the production of recombinant proteins in CHO cells carries the same risk profile as transgenic milk protein production. That is a distortion of reality and correpsonds to the contribution of a disservice to this board. Therefore I told you that you were full of crap. There's your recap, bud.
You brought up the comparison to CHO cells (not me) when you said the following:
The same issues are in play for purification of proteins or antibodies from CHO cells (Chinese Hamster ovary). It may be worse since they must purify from lower yields in the initial stages. To grow tissue culture cells, the media also has additives such as calf serum, antibiotics, hormones.
Now you're trying to change the argument on the fly.
The study examined results from 22 healthy adults who reported to have never used cocaine. The investigators administered a small, medically approved dose of cocaine nose drops to the study participants, which doubled their sympathetic nerve activity.
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My guess is that they did not have a problem with study enrollment.
There are many similarities. Yes tissue cells are in a more controlled environment but there are still issues, and I was referring in part to the idea that any DNA or RNA would somehow be a problem in isolating protein from milk as opposed to tissue culture cells, which is not he case.
Second, you really are exaggerating when you say god knows what pathogens. The goats are not roaming around on a farm mixing with other animals in the wild, but rather they are in a very controlled environment. You are far more at risk from humans by mixing in large crowd or confined space, say a sporting event, party, subway or airline. Sending your child to school or daycare exposes you to a hell of a lot of dangerous pathogens.
Third, if you are worried about goat proteins contaminating rATIII, then you should also worry to some extent that hamster proteins will contaminate CHO cells derived proteins.
I do understand that the general uninformed public may have issues, but that will be overcome with time. Especially if the DIC indication comes through. Nobody is going to worry about goats milk derived proteins when you are facing a 50% mortality rate unless you take rATIII.
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To your first point, the FDA has approved CHO cells as an expression system, hence it's validated and the technology/process development has been worked out. It's a known entity. Many, many approved biologics are expressed in this format, and many more are in the clinic. Once a master cell bank is obtained, the degree of product heterogeneity in this process is neglible. Let me break it down for you, to the FDA, heterogeneity in a manufacturing process is bad, homogeneity is good. In regards to DNA or viral contamination, the bottom line is that the FDA is convinced that it's not a problem for CHO cells. The verdict is still out on GTCB's expression format.
To the 2nd point, I still submit that there is a far, far, far greater concern about heterogeneity and contamination when dealing with a herd of animals than a fermentation culture of CHO cells. Mother Nature is an extremely powerful force and she has ways of wreaking havoc in a manner which you never imagined. However, as I stated before, I believe that GTCB's scientists have overcome this risk, and in this case, it's a good thing, because this risk is the single most important reason that we all have been able to purchase this stock at a very nice discount.
To your 3rd point, we all hope that the DIC indication (in your words) "comes through". The market certainly is huge and we would all make at least 10X on our investment. The problem with sepsis is that basically the body is in full blown nuclear meltdown. It's a very risky indication where many compounds have failed. There are a lot of unknowns.
I have been in this game for a while and it's my personal philosophy that companies with interesting new technologies should not compound their risk by applying their technology to difficult or intractable targets. Having said that, the DIC sepsis story is tantalizing. Gotta run...
The same issues are in play for purification of proteins or antibodies from CHO cells (Chinese Hamster ovary). It may be worse since they must purify from lower yields in the initial stages. To grow tissue culture cells, the media also has additives such as calf serum, antibiotics, hormones.
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I wouldn't say the same issues are at play. Note even close.
Tissue cultured cells that express recombinant proteins are contained in a far more controlled environment than a herd of goats, which are exposed to God-knows-what in terms of environmental pathogens.
Basically there are a panoply of additional risk factors associated with production of proteins in a herd of transgenic animals vs. a culture of transgenic cells.
If there wasn't, GTCB would be valued at about 100X what it is now. Seriously.
The reason why I am a shareholder (at this valuation) is because I believe that GTCB can overcome this issue. Simple, really.
Interesting, it looks like their following in the footsteps of the their lead program- the digestable crystalline formulation for pancreatic insufficiency.
RE: DNDN
I should have paid much more attention to the stock sale by Gold. That's all you need to know right there.
Although it is not a lot of money, when you consider that he even bought some today under not so ideal market conditions and that he has already plenty of shares and options, there is no other way to interpret this except as extremely bullish. At least this CEO is ready to put his money where his mouth is...
Hey 50 grand is 50 grand. I agree that this is a very bullish maneuver and love to see when a CEO loads up on his own stock- especially when the Street undervalues it so much. I also got the warm fuzzies reading the transcript of the latest conference call. I believe that the future of this company lies in the production of Mabs and FOB's and I appreciated that mgmt stressed this point/approach in the call.
I know the FDA knows this, I just hope the company stresses the alternative MOA.
All that about nevido is well and good, but it doesn't change the fact that exogenous testosterone, will shut down the testes.
Androxal stimulates the pituitary to turn on the testes and make more on their own.
A world of difference if you want your testes functioning normall instead of becoming totally dead and sterile.
Completely agreed, in the upcoming FDA meeting I really hope that mgmt stresses the different MOA of androxal vs testosterone. To me, this is what makes Androxal so compelling.
Altus is definitely a company to watch, but Im not buying in until they get a little closer to news. However, I'm intrigued by their technology platform and I like the pancreatic insufficiency indication.
Thanks for starting the board up, I will be bookmarking it.
Bought in today as well. The market cap today is 250 MM (at the end of trading). At the end of the day when this company has a 1.5B- 2B market cap, its not going to matter if you bought in at a 200 MM or a 250 MM, or a 300 MM market cap for that matter.
Thoughts on JAV?
I've been watching JAV from a distance, waiting for the price to level off in order to buy in. What is going on here? This doesn't just seem to be "summer doldrums" to me. I believe in this company and their technology, but cant come up with an explanation for the hammering it's taking. Thoughts?
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The management inspires significant doubt among many investors. For good reason, although I view it as ancient history.
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Agreed,it's ancient history for me as well. According to the latest corporate presentation, the Street is coming around as well. It's pretty heavily invested-in by some big-time players:
Filing on 10-27-06
Total Reporting Shares: 5,993,082
HBK Management LLC 943,400
ProMed Management LLC 843,485
Great Point Partners LLC 721,100
Xmark Opportunity Partners LLC 698,739
Efficacy Capital Ltd 672,528
UBS Securities LLC 628,801
Quogue 605,754
Caxton Associates LLC 177,505
Barclays Global Investors (CA) 111,424
Joseph Podolski 100,881
Vanguard Group, Inc 89,928
Balyasny Asset Management LLC 80,000
Perceptive Advisors LLC 78,127
Morgan Stanley & Co 78,700
Louis Ploth 32,722
Others (12) 129,988
Filing on 4-5-07
Total Reporting Shares: 4,787,493
Efficacy Capital Ltd 1,014,128
ProMed Management LLC 663,144
Balyasny Asset Management LLC 595,000
FrontPoint Partners LLC 562,426
Great Point Partners LLC 407,900
Wall Street Associates 275,000
Caxton Associates LLC 254,215
Barclays Global Investors (CA) 153,849
Joseph Podolski 106,381
Pequot Capital Management 104,000
Citigroup Investment Research 100,000
Vanguard Group, Inc. 90,174
Portolan Capital Management 83,412
Columbus Circle Investors 79,967
GRT Capital Management 62,880
Fred Alger Management 46,591
Louis Ploth 35,717
Lehman Brothers, Inc. 35,534
Northern Trust Global Investments 24,826
Others (14) 92,349
Ive been watching BMRN in the hopes of getting it at a discount. No such luck, apparently.
Every company has warts. What are the warts here? I just cant seem to find any.
1. Very compelling clinical data in two distinct programs.
2. Clear unmet medical needs for both.
2. Big markets for each
3. Experienced mgmt. team
4. Strong evidence of insider buying since '06
I've been in this game for a while. What am I missing?
As I mentioned, I believe this stock is undervalued so I put my money where my mouth is and bought in today. (I also bought some RPRX on good safety news and ZGEN on the cheap). Take Care everyone (even you, DD).
Bought another 800 shares at 12.87. Best deal in Biotech right now.
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LOL this excedes ridiculous. Give him one more aliais Mabad. The fact we have people on this site that were taken in by this guy is embarrasing. Low point in his comments was his attack on Atryn's use in DIC by dismissing the results as pertaining to a "subset" of patients. Yeah they were a subset alright, those who received AT3 without Heparin. This group was identified by careful analysis and showed a 14% increase in long term survival. This is hugely significant and unless shown to be in error by studies will indeed turn Atryn into a blockbuster drug.
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I expressed concern about the risk involved in starting a clinical trial in sepsis (the graveyard of many a program) based on a subgroup analysis of a previous clinical trial, and you're the one laughing? You obviously haven't been in this game very long. I also stated that the sepsis program "is tantalizing" but that "I'm not pinning my hopes on it".
It's amazing how there appears to be a zero tolerance policy for any critical analysis of this company's programs and/or technology. Talk about group-think. It's like the DNDN board.
As I stated, I believe that the future of this company involves mAbs and FOB's. That's all. And it's undervalued at that. It's called objectivity. Look it up. I would encourage you to try and be a little more open-minded.
I dont see the Factor VII program panning out… Atryn… Thats a real blockbuster there. Oh I forgot, it's going to cure sepsis. My bad… Then there's antitrypsin… Hmmmm.... ok. Sounds like another blockbuster… albumin. Oh wait that program's been shelved…[blah blah]<
Thanks for making it patently clear what your mission here is.
You can selectively edit my posts all you want, but they dont change the facts or my objectivity. This company has great technology, revolutionary in fact. Ive seen this time and time again, is the technology being properly applied? Where is the money going to come from? You've said it yourself in your own posts, GTCB should get about 6-7 MM in revenue and 4 MM in profit from Atryn sales for HD, you know the indication it's in clinical trials for. If you go back and read the original post, you would see that Im not blindly bashing, Im asking tough questions about this company. If you disagree, prove me wrong.
Welcome to the board, Vin.
>[To Pre_Clinical]: It is too soon to dismiss Factor VII and you have no idea how well any second generation Factor VII will pan out.<
Quite true. In fact, one of the second-generation FVIIa programs touted by Pre_Clinical — MAXY-Seven from Maxygen — is not doing so well. Roche recently pulled the plug on this program and returned all rights to MAXY (#msg-17854630, #msg-19911920). Regards, Dew
Nice distortion, Dew. The original partnership between the two parties gave 2nd generation FVIIa rights to Roche for acute indications/trauma only (http://www.biospace.com/news_story.aspx?NewsEntityId=4972 ). Under the terms of the deal, Maxy wisely retained all rights to hemophilia, (a billion dollar market with a clear clinical path, and validated experimental models of disease}. Roche terminated the partnership because there was no clear clinical path for FVIIa in acute/trauma situations. As MAXY stated in their latest conf. call, they plan on entering the clinic early next year with their 2nd generation compound. Having said that, Novo Nordisk's compound is the one you really should be worried about, they've only been working on Factor VII for Ummm, 20 years.
But hey what do I know.
jessellivermore is quite right—GTC will pick its spots judiciously. GTC does not need to go head-to-head with CHO-cell manufacturers will nilly because there are plenty of cases where drugs either can’t be made in CHO cells or can’t be made in CHO cells economically. FVIIa is an example of the latter.
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Lets go over all of GTC's programs. For reasons stated below, Im pinning my hopes on the FOBs.
First, Factor VII (since you mentioned it already). Factor VII has to be manufactured in Vitamin K supplemented BHK cells due to its extraordinary difficult to express GLA domains. Yes it falls into the category of "difficult to express" (I would like to see the transgenic rabbit produced material's in vivo efficacy). Yes its a huge market. However it's all besides the point, Novo's 2nd generation FVIIa, NN1731 is coming down the pipe and MAXI goes into the clinic with their's next spring. The improved players are already in the clinic. I wouldn't pin your hopes too much on a 1st generation Factor VII at that point in time. Im not sure how you can call this a "judiciously picked spot". I dont see the Factor VII program panning out.
Second, there's Atryn. What is that going to bring in, 5-6 MM per year after the partnership? Thats a real blockbuster there. Oh I forgot, it's going to cure sepsis. My bad.
Then there's antitrypsin. What the heck is the indication?I read that its being licensed to a dermo for elsatase induced skin lesions. Hmmmm....ok. Sounds like another blockbuster.
What's next, albumin. Oh wait that program's been shelved too. Apparently you can produce metric tons of it in yeast.
So that leaves us with the mAbs and FOB's. I think this is where the company really has a lot of potential, both in terms of COGS and especially if this ADCC enhancement observation pans out. Unless you're betting on the sepsis indication for Atryn. While its tantalizing, Im not holding my breath on a subgroup analysis of the Kybersept study.
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GTCB did produce Mabs for Abbott and Elan in transgenic goats if my memory serves me correctly. I believe these were derived from cell line sources as well. It is not clear why these collaborations were not pursued further. A speculation would be that if a company has a CHO-cell line protein that works they would go with that platform as it is tried and true. This does not mean that it is better just easier for the company to implement with existing facilities and personnel. Also at the time of these collaborations GTCB had no approved product.
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I agree completely and have found that in my own personal experience as well. Ive seen several instances of companies building up huge CHO cell capacity and then searching for programs to fill the gap when their internal ones fail. If it wasnt something that expressed in CHO's, they werent interested.
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If GTCB/Abbott/Elan has such data comparing their goat derived Mabs with the cell line derived product I doubt that it would be made available. The purpose of these companies is not to get pubs in Nature Biotechnology but to produce profit from patented technology to their competitive (i.e. proprietary) advantage.
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I agree here... to a point. Of course the purpose is to produce profit, not merely publish. However, companies with groundbreaking new technologies can do themselves a huge favor by publishing in top quality, peer reviewed journals. It adds a lot of credibility. For example, Glycofi's papers describing their technology platform were flat out amazing research articles and went a long way to establishing credibility and a buzz for the company.
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In addition one of the foci of GTCB is to produce proteins that are difficult to express in cell systems. They may have to compete down the road if another company decides to produce the same protein in a cell line as they are in the goats. However if they choose wisely (and IMO they have) they won't be competing against CHO-cell derived proteins in the near term. There are plenty of targets in the plasma protein arena that require large quantities of material for therapeutic use that cannot be served by cell systems.
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Fair enough, but the company is putting a mAb into the clinic next year and placed a large emphasis on FOB's in their Venn diagram corporate strategy slide.
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I am a supporter of Dew and am also concerned about possible hidden agendas. It also seems PC is fluent in CC tech. We all form opinions none of which necessarly reflects absolute truth. It is possible for a post to reflect a certain amount of science yet create confusion and dissention by raising issues which are truly irrelivent. Or by another tack create immaginary goals which are unrealistic and do not in any way reflect the goals of management, but if these imaginary goals are excepted by readers lead to the conclusion the company has little chance of suceeding.
For example: The issue Atryn's glycolisation patterns has been rendered moot by the decision of the EMEA. The simple answer is they are ok.
For example: Replacement of CHO cell culture protein production by transgenic goat production is not one of GTCB's goals. Cell culture production is deeply entrenched with previously mentioned layers of bureaucratic resisence and livlyhoods on the line not to mention tradition. The horse was not replaced overnight. GTCB will do very well operating where no cell culture dares to go. Believe me, there is plenty of room. Will GTCB eventually replace CC. No one knows.
Who controls the Spice, controls the universe.
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Hmmm.... now this is a very interesting statement. Look fella, I'm here to inquire about specific questions that I have regarding this company's technology platform, in order to mitigate my risk as a potential investor (as much as possible). If you've read through my posts, all Ive done is ask for data. Now if that data doesn't exist because its not public info, then fine. I will take that into consideration if/when I pull the trigger.
Now, in doing this diligence (publicly on this board), you've accused me above of obfuscating what I like to call "the truth". Well, what is "the truth"? The conventional wisdom on this message board? Is that "the truth"? To illustrate this point, lets take your example above. You stated, "Replacement of CHO cell culture protein production by transgenic goat production is not one of GTCB's goals." I couldn't possibly disagree more with this statement. If you've seen the company's latest presentation (squarely front and center on their home page), in the Venn Diagram "Strategy" slide, there is a huge circle called Fob's or follow on biologics. Please review the README section for a summary of follow on biologics, and then go find out how these proteins are currently being made. In addition, the company has stated it plans on entering Phase 1 in 2008 for the CD137 mAb. Got that? Next year they're putting their first mAb in the clinic. mAbs are typically made in CHO cells. It's abundantly clear that this company has placed the CHO cell expression technology squarely in its crosshairs. Therefore, in regards to the topic of Fob's and the company's own clnical candidate, I dont think its at all unreasonable to ask for a PK/PD comparison of material derived from transgenic milk and CHO cells. That's all I asked for!
Now on to your other point, "The issue of Atryn's glycosylation patterns has been rendered moot by the decision of the EMEA. The simple answer is they are ok." Again, I couldnt disagree more with this statement. As it turned out, the form of Atryn produced in transgenic milk is underglycosylated, and consequently more rapdily cleared. The company themselves admitted they got lucky with this indication, in that the rapid clearance is probably more beneficial. For Atryn, the inconsistent glycosylation didnt appear to affect safety or efficacy, hence the EMEA approval. Now, this result with the company's most advanced compound did lead me to inquire about the degree to which the goat mammary gland secretory pathway diverges from other expressions system, validated ones in particular. I still havent answered my own question, but when if/when I do, I will be sure to share it with the board.
PS- I could really care less if you do or don't "support Dew Diligence" or find a hidden agenda in my posts.
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>So the question is, how common is this, and to what degree does the mammary gland glycosylation pathway differ from other expression systems, in particular CHO cells?<
That's a pretty poorly designed experiment if you're trying to figure out if the PK/PD of goat-derived material is the same as the stuff currently used in the clinic.
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Thanks for your input. I'm trying to evaluate the promise of this company's technology platform as a potential investment. Do you know if an any data exists which compares the PK/PD profiles of a set of goat derived recombinant proteins vs. the same set of proteins expressed in CHO cells? Thanks in advance. -PC
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Expression level is a separate issue from glycosylation variants. (The latter is a red herring, IMO.)
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You can think that all you want, but show me the data to support your point. All that Ive asked (rather politely mind you) is to see a table of proteins produced both in goat milk and CHO cells demonstrating bioequivalent PK/PD. What we do know is that for the company's lead protein, Atryn, the in-vivo half-life is shorter than the dominant form found in plasma. This was due to a difference in glycosylation state. So the question is, how common is this, and to what degree does the mammary gland glycosylation pathway differ from other expression systems, in particular CHO cells?
And sorry, quotes from mgmt that say, "Dont worry" aint gonna cut it.
Wow. You have quite the imagination, Dew Diligence. Based on the advice from numerous private messages, I think I'll take the high road.
aslan2772, thanks for the reply....
You said,
<<<<<For the sake of argument, if GTCB wanted to produce exclusively antithrombin alpha, all they would have to do is make a point mutation, converting serine 137 to a threonine, creating a NXT consensus sequence. This would most likely work just fine.
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I think you've presented a fairly reasonable hypothesis for testing. I guess my point still is, that , it's not that easy.
1. The proteins were tested in insect cells, it's most likely that secretory pathways between goat and insect are quite divergent. Just because one achieves more efficient glycosylation in one organism doesnt mean its going to translate to another.
2. Your mutation has now altered the natural primary sequence of the protein. I know its just one carbon, but Ive seen a valine to an alanine substitution alter protein activity 10-fold. You have to make sure activity of variant doesnt take too big of a hit.
3. Any time you mutate a protein away from its natural sequence, you raise the stakes in the immunogenicity game, (although it's not a factor here, because this an acute indication)
4. You're also assuming that residue is not patented by the original discoverers.
5. The point you raised about the goat expression timelines is EXCELLENT. Because of the work/time involved to set up a transgenic goat, you don't want to use a goat to start screening variants.
Thanks so much for the thoughtful reply. It's FAR more stimulating conversation than, "GTC scientists are smart, they'll figure it out".
Take Care, PC
floblu, as you probably know, GTC’s ADCC patent application is cited in the ReadMeFirst, which Mr. Pre_Clinical claims to have read. What I’m trying to say is that I don’t think Pre_Clinical is looking for information. Regards, Dew
What am I looking for then, guy? Look Ive been more than cordial with you, but you're comments, quite frankly, have been rather glib. And it seems like you take a lot of what the company says at face value. That doesn't sound like good Due Diligence to me. In fact, you didn't know until today the reason why the company's lead compound has a shorter half life than the plasma material. You're handle says "lets talk biotech" but it certainly doesn't seem that way.
Thanks for the kind words Mabgoat, glad that I can be of service.
Speaking of the high cost of biologicals, there was just an article in today's bio world which discussed the fact that the English healthcare system wont even cover a lot of the big market Abs. Something's got to give here, and I believe it will come with breakthroughs in protein expression technologies like GTC's.