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zipjet,
FRE/FNM and, by necessity, the US Gov't, are the remaining bag holders in the worst looting of equity ever seen in our history. Remember that FRE/FNM were limited by their charters to only purchase conventional, documented loans. Exceptions in their portfolios were federally mandated, affordable housing programs to put home-ownership within reach of those with lower economic status. Congress, unable to expand HUD/FHA budgets, went to the GSE's to bring more citizens in on the "prosperity". Still, these programs were tiny compared to the overall book of the GSEs' normal business. Furthermore, those in-house programs of the GSE's are completely eclipsed by the enormity of what commercial banks and retail mortgage people did out in the wild west mortgage market. You must differentiate a key point: that subprime was not the GSE's doing. As the banks pressured their way to gain additional market share of the secondary mortgage market, the instruments they sold became increasingly based on shakier mortgages. And I know that is a massive understatement. The secondary market's former quality was ruined by the explosion of defective issues being auctioned. Ratings agencies and federal oversight were asleep at the helm or kept a blind eye in order to process the volume and maintain the revenue flow. Additionally, there is a very significant foreign investment component to this situation. Pressure to get this under control is coming from around the globe. Another point: deflation of asset values is the main issue about solvency. The original, underlying home values that decrease (as home prices fall in this spiral) has to be GAAP quantified. They are more of a factor than mortgage defaults. The GSE's revenues are sufficient to pay bond investors' their interest and it's not a funny reality that even though people are paying their house payments, the fair market values are putting them underwater. The conundrum here is we're essentially calling these homeowners "insolvent" too; obviously, nobody who makes their note will be kicked out of their home. Cashflow through the GSE's is sufficient at this time to pay the bond investors. The bridge that will be required is this deficit in home value versus mortgage amount. The GSE's are the last men standing, and doing what their charters and corporate missions require: maintaining liquidity in mortgages. Their reserves are designed to weather severe economic downturns, but we see that, of course, they are not unlimited. While the commercial banks can cut and run, there must be a time where the merry-go-round and the buck has to stop. If Paulsen hands over the last vestiges of the GSE's to Wall Street, the looting will be complete.
Sorry, THANKS BIO PETE. --But hey I appreciate lidopete's posts too! --RMc
Thank you lidopete and dewophile. I guess this inquiry into platelet function was not yet investigated by original trials of diclofenac? Is it unique to Javelin's formulation or just smart of them to put it up there now, in a head-to-head comparison to improve the label? --RMc
Can someone help me understand this new trial that recently began? Why are they "assessing platelet function"? --RMc
http://clinicaltrials.gov/ct/show/NCT00548678?order=3
Sorry, defective link. Here's a better one:
http://www.isis-innovation.com/news/articles/Geron.html
How about the future connection between stems and immunotherapy? The ultimate DC vaccine: production capability as scalable as pharmaceuticals, immuno-priviledged for all patients via tolerization, universal activity against all cancers? Isn't it beyond theoretical at this point with proof-of-concept being accomplished with adult stem cells? The individual, allogenic version of this vaccine has cleared circulating prostate cancer cells in patients’ blood, extended PSADT to 100 months and produced major CD8 and CD4 T-cell immunity levels in PhI at Duke. The WARF basic stem patents may go down, but the more specific IP on cell differentiation protocols, methods and use claims, defined growth media, etc. should endure. Anyway, this is one stem cell application I’m looking forward to:
http://www.isis-innovation.com/news/news/geron.html
Preciouslife1,
Did you listen to Geron’s CC the other day?
http://biz.yahoo.com/cc/1/78821.html
CFO’s discussion until 7:58 minutes, then discussion of GRN163L early results presented at NCI-AACR/ Prague and December’s ASH. At 11: 47 minutes, CEO Okarma brings up lab data on 163’s effect on cancer stem cells in myeloma and says it may be the first drug known to knock them down. --RMc
From the editor of the NEJM:
http://content.nejm.org/cgi/content/full/355/12/1189
I would love to know the source of this T activator. Have there been any patent app's anywhere? --RMc
Bob,
What I gather on the CEGE vs Merck virus platforms is that they do work differently while they both use telomerase in their targeting. The layman version from what I can put together is that Merck uses adenoviruses to teach the immune system to go after targets (say, telomerase positive cancer cells) and much differently, CEGE's oncolytic virus goes around and replicates only inside of T+ cancer cells (destroying them from the inside out). The oncolytic virus concept is a direct killer. You can see the immunological synergies with Geron's GRNVAC1 (using DC's) and Merck's vaccine programs. I've read that there is a significant part of the population with built-in immunity or "readily" capable immunity to the adenoviruses (they are mild compared to other viruses), so tweaking the formula later is necessary if you want to keep using it.
Probably not the silver bullet cure, but just think if a vaccine is effective enough to extend survival times when added to conventional standard of care. Think of the potential if trials of stand alone mono use find it matches survivability of current SOC without the toxicity. --IMHO, RMc
Dude,
Mainly, I wanted to welcome nerdseeksblonde. There is no hidden agenda. --RMc
Dude,
Try not to get hung up on the "us vs. them". There are many Pub Med abstracts from the last few years that point to telomere instability as a starting point for cancer, particularly liver. Nerd is right, it is complicated and possibly contradictory that you want to inhibit telomerase knowing this. But I think Geron has more insight on the issue, and furthermore, they aren't the only ones working on TI. The issue isn't new. To date, all kinds of pre-clinical work has been done and Ph 1 in humans should settle the questions. NSB brought us a link to fairly recent 2006 study on the matter; and as an investor, I want to read what *anybody* with scientific insight has to write. --RMc
Welcome nerdseeksblonde,
I hope you continue to post here. Your scientific expertise will be highly regarded by those of us who have read your posts on the Biotech Values board.
The study you posted indicates telomere dysfunction creates a situation favorable to the formation of liver cancer cells, notably if P53 levels are low.
I hope that model isn’t the whole picture, but it does point out the fine line Geron is walking with telomerase in their inhibition and activation programs. --RMc
Bad link, try:
http://80.247.210.88/ciw-06ena/
then type "GRN163L"
Bob,
Here is the R&R weblink:
http://www.wsw.com/webcast/rrshq10/gern/
(c/o Dew from iHub Biotech Values board. High quality bio discussion over there)
--RMc
Dew, here's more on ESC's. Additional installments of esammee's transcript of Geron's recent CC are available at the iHub GERN board:
DR. OKARMA: Thanks, David, and good morning everyone. Thank you for dialing in this morning. In my comments I'll pretty much follow the order of events that are in today's press release in terms of third quarter highlights. So first, starting back on the 5th of July when we press released a summary of about a dozen presentations that our people and our collaborators made in Toronto at the ISSCR annual meeting which is really the year's main event for stem cell research. First, turning to our lead stem cell program, the OPC1, or glial cell for spinal cord injury, we presented some important results that define a second mechanism of action of these cells. You will recall that we have demonstrated exuberant myelination by these human cells when they're injected into an animal model of spinal cord injury which is the reason for the animals' persistent and dramatic regain of locomotor function. But in addition to that remyelination, we've documented that these cells appropriately secrete both in vitro and in the animal spinal cord injured tissues neurotrophins. These are biologicals which impact axonal sprouting and survival. So in vitro we have identified a number of neurotrophin factors that these cells secrete, including TGF Beta 2, although there are others, and in vivo we have over 2-1/2 times more neuron survival and sprouting in the tissue that receives OPCs compared to controls. So this is really important and the significance of it is that these neurotrophins which clearly have activity in vivo will significantly enhance the development of alternative new circuitry in the lesion in addition to the myelination effect which would restore axonal tracks that are in fact intact. So, in sum, these cells actually provide to the injured spinal cord literally all of the appropriate stimuli that are required for repair. That's a really important finding.
A second paper described the scalable production of these same cells, OPC1, from our master cell bank. So this paper demonstrated a production process that's completely consistent with current good manufacturing processes - which is made from our pathogen free H1 ES master cell bank. If you recall, our master cell bank is made from a cell line that is fully qualified for human use and the cell bank is maintained without feeders, without any serum and contains only human or highly purified recombinant reagents, namely, a completely chemically defined media. We demonstrated over 9 months cell survival in the animals with spinal cord injuries - that number is now out to 12 months, which is an important point to document the permanent nature of the survival kinetics of these cells after they are injected into the spinal cord injury.
The last point in this presentation is that the scalability of the process is quite good. Today we can make over 2500 full doses of OPC1s per run and that scale is easily increased.
Thirdly, on the OPC1s, and this is an issue that of course crosses all of our ES derived cell types, has to do with the potential for immune recognition of the cells after they are placed into human subjects. In ‘04 in Stem Cells we published that the undifferentiated embryonic stem cells are immune privileged – namely, they are not detected by human T cells, B cells or sera. This presentation extended those results and showed that the OPC1 product, the very cell we plan to inject into patients is also immune privileged and shares exactly the same characteristics as the undifferentiated line from which it's produced. So the OPC1 does express low levels of Class 1 antigens, but no Class 2 – just like the undifferentiated ESCs. Functionally, there is no reactivity of the OPC1 in a standard mixed lymphocyte reaction from multiple disparate donors, there is neither any activity against human NK cells and sera from over a dozen different individuals had little or no lysis effect in vitro on the OPC1s, and that addresses the misinformation that was published a year ago about these cells potentially being contaminated with murine cyalic acid residues. We find no evidence of that on our lines, directly or indirectly. And all of these immune privileged data were repeated with multiple GMP production runs of OPC1. So we are highly confident now that the low dose cyclosporine transient immune suppression will completely prevent immune recognition of these cells in vivo until the actual lesion heals or a course of a few weeks post op at which time once again the cells will be in the immune protected central nervous system.
Turning to the islets for diabetes. This poster really documented that we have the cell. These islet-like clusters produce insulin which is responsive to glucose concentrations, as well as glucagon and somatastatin, the three main islet hormones. They also express the right transcription factors, giving us a pretty elegant molecular fingerprint that these are the right cells. These cells are now highly enriched, both by sieving and by a more precise production method and are now in Canada at our Edmonton collaborators in the animal models of hyperglycemia, so stay tuned for more news about the in vivo activity of these cells later in the year.
Turning to cardiomyocytes. We've now moved that cell type into the second position for entry into the clinic behind the glial cells. We've demonstrated now scalable methods to produce cardiomyocytes in a very similar serum-free and defined growth factor containing medium as OPC1. There are again no co-culture steps and we achieve now 80 percent purity of cardiomyocytes without any further purification steps. We've demonstrated that these cardiomyocytes can be frozen and thawed and they retain the same electrophysiology, drug responses, and in vivo survival activities as cells injected into animals without prior freezing. These cells have now been adapted to our MCB production methodology and cells made that way when transplanted into the infarct zone of infarcted rats engraft, survive and clearly prevent heart failure. Later this year we expect, or early next year, a publication documenting these effects using ECHOs as well as MRI. It's really a, a seminal paper and I think will show proof of concept for the cardiomyocyte prep that is as elegant and compelling as last year's publication of the glial cells in the spinal cord injured rat model.
We had a few other publications from the Geron Bio-Med operation in Edinburgh that focused on liver cells, further characterizing their molecular markers and their function and the first demonstration that osteo progenitor cells – cells that form bone in vivo – are capable of repairing a full thickness, critical size skull lesion in animals with much greater degree of closure than derived from mesenchymal stem cells as a comparator.
So these papers really emanate and sort of document the multiple shots on goal that we're creating in the embryonic stem cell side of our business which are protected by 63 issued or allowed embryonic stem cell patents and over 221 patent filings worldwide.
Thanks esammee.
Recently, in the SNY/IMCL/Yeda case, a district court did award patent ownership to Yeda scientists that were not part of the initial patent application, based on their lab journals showing earlier inventor notes. There is a question of whether the district court had that authority, and whether *now* the concept will be deemed unpatentable since it got produced from the public domain. The Yeda scientists' may have killed the goose that layed golden egg as it were. Obviously, here on the Geron board, we're talking about a reexamination and it's not the same thing as an ownership dispute, but the outcome could be similar: no patent. With WARF composition of matter declared obvious or too broad, Geron's method/ differentiation patents could move up in the food chain. I think those could even be patentable in the EU, but are still pending the review of being separate from ESC composition of matter. Who else has described a GMP ESC bank and scalable, pharmaceutical-style production of cell therapies? (I don't know and I presume we'll find out shortly). Interesting link on patent reexaminations:
http://www.bakerbotts.com/infocenter/publications/detail.aspx?id=937e69ee-495b-4404-8f71-0923dc20e0a...
100% agree. How well do you think WARF will defend against the allegation of the existance of prior art? All patents are filed with a "background of the invention" section to assert how their claims are different, yet they describe prior art. Composition of matter may fall. --RMc
WARF stem cell IP is in serious danger, pages 6,7,8 :
http://www.consumerwatchdog.org/resources/5843780.pdf
: ) Chromatin transfer, Fusion NT, Micro-injection NT, transgenic biologics... this is 99% of animal cloning, yet to be profitable I think they must stay strictly an IP licenser. Scott Davis has a great background, but unless there's serious revenues rolling in, I don't believe he and stART will be directing any projects unless they involve absorbing more IP. --RMc
I wish I had bought more during those times. Geron's financing was brutal to the share price yet I always had the feeling that "The Science" (apologies to alpha) would get them to higher ground. woofs caught a good bunch of shares in that range. Lately, I've become concerned that the therapeutic goal lines keep moving higher from advances in other targets by biotech and pharma (not to mention others now knocking on telomerase's and stem cells' door). Clinical trials are tough to enroll for these competitive and other reasons, but on the other hand, I am impressed with Geron's relationships with heavy hitters and thought leaders in their disease categories (Ratain, Rai). I think the high road with "The Science" is the way to go, yet strong IP can keep the barbarians at the gate for only so long. I am eager for trial results at this point; we should get a idea of enrollment progress sometime this Fall. I keep checking the ASH and EORTC (Prague) Meetings for accepted abstracts, but nothing so far. Ratain, Clarke( cancer stem cell guy) and Kelland (telomerase) are featured at EORTC. Rai, as president of ASH, will of course be prominent there. We shall see if Geron is ready for primetime (a SNL timestamp there).
Hey BTW, I don't think stART is doing anything but an IP land grab. Licensing animal cloning could be valuable, not as rich as Qualcomm or as ubiquitous as cell phones, but probably worth the few million in investment. Geron and ACT aren't into animals, and the world isn't ready for human NT yet. GTCB (and Dew), I think, deftly sidestep that Atryn "doesn't use the UMass IP" yet they are licensees of ACT. Does that mean the founder animals in the herd require the cloning IP and separately, Atryn is "later" produced, using IP involving biologics (antibodies/proteins/enzymes) production from transgenic milk? I think stART is right in the middle of everything. --RMc
I enjoy your posts essamee. I wonder if maybe UMass/ACT/Geron/stART goes like this: Sperling told the lawyers to ask how much they'd take for animal cloning; he had 75 cents laying around. ACT, between a rock and a hard place, chooses between getting nothing or getting something. Remember, they'd be out the license fee to UMass. Consider in the big scheme of things that stART IP is: Roslin, PPL, and now UMass! Rather than destroy the UMass patents and claims by winning the interference (like when Geron crushed Infigen), stART retains the IP value and it's "scientific reach". Maybe our boys are smarter than people think. UMass IP worth up to $1.25? Read about ACT's sublicensees for the UMass patents: GTCB and through them, Pharming. I expect West was bright enough to negotiate license cost plus % of future products like Geron,WARF and everybody else does. I note GTCB's goatmilk-derived Atryn is now approved in Europe. There is value here or it might be the Shiraz again. --RMc
Here is a pre-clinical immune system enhancer currently testing in a "HIV setting" (ex-vivo cultures, from three donors). Slim on MOA details, but telomerase is increasingly showing up as a research target in Immunology, Oncology and stem cells. Disclosure : Long Geron. --RMc
http://www.pipelinereview.com/joomla/content/view/3299/112/
July 2006 Nature article from Shay/ Wright. Discussion of a telomerase role in the cancer stem cell (CSC) at the end. Disclosure for both authors is linked as they are scientific advisors to Geron. --RMc
http://www.nature.com/nrd/journal/v5/n7/full/nrd2081.html
Gardasil, Merck's new HPV vaccine to prevent cervical cancer costs $120/ shot. --RMc
I think it's a good move, you'll love it at $100. --RMc
Interesting interview with the CEO of Geron's new PR firm:
http://prmachine.blogspot.com/2005/05/euro-rscg-life-pri2i-interview.html
--RM
Dew,
This is what bugs me: you know what it costs to deliver new therapeutics. WARF is completely within bounds to demand an upfront payment and future royalties for commercial use. $75,000 -$250,000 is peanuts for commercial rights and academics already now have access to stem cells for FREE. CIRM and the rest of these so called "researchers" need to stop whining and pay up. I wonder what's the difference between these scientists and another type, say geologists, venturing out and prospecting for new oil. Sorry if there's lots of financial risk involved, it's just the nature of the business. --RMc
rx,
I haven't heard anything different. Past performance and investor presentations are all the data we get to evaluate. Geron is like any other small biotech, sh*t happens. I always hope for the best and plan for the worst. --RMc
Paula,
Hi, glad to see you on iHub. This place was dead 3 years ago.(see my bold post, #18) IMHO, Geron and the FDA are still dancing around with this hot potato. Geron isn't banging on the door demanding anything openly and they are giving the FDA their due. But I hand it to Okarma that they have their act together not only by using a Bush approved cell line but also developing it without mouse feeder cells. Geron has been working with the FDA from the beginning and as you know, the preclinicals were extensive. Also you know that other stem cell research data is coming from all over the place so the FDA/ NIH are in the midst of it.
To anybody considering: Low 6's is a good buy here. If I were newly interested in GERN I'd fish in this range. Also looking for more at a lower sp with the general world situation weighing in will probably happen(and don't dismiss hijinks from the political FDA). I agree that these Geron guys know what they're doing, so it's a matter of time. The IP is coming to fruition. Accumulation window is shrinking: I expect a bump this November when good interim data is presented at ASH from Geron's oncology trials now underway. The stem cell IND data submittal is supposed to be 1Q 2007.
March 2006 Wired interview with Okarma:
http://www.wired.com/news/technology/medtech/0,70521-0.html
--RMc
Here's a competitor (or a contract manufacturer?):
http://www.drugstore.com/qxp83219_333181_sespider/twinlab/mega_b_12_dots_5000mcg_sublingual.htm
Questions for Marty:
1) How will Cobalis be able to keep competitors' B-12 from diluting sales? If the only active ingredient is a well known, completely ubiquitous vitamin, what is it about PreHistin that will cause 4 out of 5 doctors to recommend it?
2) I realize the OTC market is huge, so what is your estimate, cost-wise, to capture customer loyalty with your brand?
--RMc
Current buying opportunity should not be missed. Attempt by AF to smear GERN will fail ultimately. The science is stronger than the media. --RMc