+ 12,3 % bei Geron (902213) Was ist los? o. T.

MENLO PARK, Calif., May 12, 2004 (BUSINESS WIRE) -- Geron Corporation (GERN) today announced that a presentation of additional results of the Phase I/II clinical trial of a telomerase cancer vaccine will occur at the American Society of Clinical Oncology Annual Meeting on June 6, 2004 at 3:45 p.m. as part of the Developmental Therapeutics: Immunotherapy program. Johannes Vieweg, M.D., Associate Professor of Urology and Associate Professor of Immunology at Duke University Medical Center and principal investigator of the clinical trial, will be giving the presentation.

Geron is a biopharmaceutical company focused on developing and commercializing therapeutic and diagnostic products for cancer based on its telomerase technology, and cell-based therapeutics using its human embryonic stem cell technology.

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Rodman & Renshaw Techvest Healthcare Conference
May 13, 2004
www.wall streetwebcasting.com/webcast/rrsh/gern/

Presenting company Geron. Geron is a pharmaceutical company dedicated for cancer vaccines using the telomerase technology as well as cell therapeutic products based on their stem cell technology. Presenting for the company today is Dr. Thomas Okarma. President and CEO of the firm.
DR. OKARMA: Good morning and thank you for coming. Today I'll be giving you an update on our telomerase based programs in cancer and our stem cell based programs for chronic disease and in that context I will of course be making forward looking statements so we call your attention to our risk factors in our SEC filings.
So to start first with the oncology platform. There are over 2,000 papers which now demonstrate the dependence upon telomerase for cancer progression. Telomerase is today's only universally and specifically validated cancer target. Our validation of this target comes first from our work in using the telomerase vaccine which has just completed a Phase I/II study at Duke. We will be presenting – or rather the investigators will be presenting the results of that trial on the 6th of June at ASCO.
In addition to our data in prostate cancer, other academic researchers have demonstrated of prostate vac–telomerase vaccines against a broad range of tumor types, again consistent with the ubiquity of telomerase in cancer. [esammnee, amazingly enough, didn't provide this transcript as he promised]
We recently announced the acquisition of exclusive commercial rights for one of the platforms in this vaccine program, that from Merix Biosciences which I'll talk about in a moment. Our second platform based on telomerase is really our home run hitter here, the telomerase inhibitor drugs. These compounds have been demonstrated to be active in vitro literally against all forms of human cancer and in 5 out of 5 human cancer models in animals. I won't have time to talk about the oncolytic virus which is under development by Cell Genesys under license from us and the bladder cancer diagnostic which is under development by Roche, again, under license from Geron. [how long will it take the thief imposter to re-post this?] Supporting and protecting all four of these programs is a controlling intellectual property estate which has a lock on both the target and the specific clinical programs.
Let's turn briefly first to the license acquisition from Merix Biosciences. We had been evaluating a number of platforms to deliver the telomerase vaccine as antigen and will still continue to do so, but we were quite impressed with the utility of the Merix platform, so we acquired exclusive rights to that platform broadly for telomerase and co-exclusive rights for other defined antigens in chemotherapy for cancer. This acquisition includes all new IP filings over the next three years; it's a fully paid up license with no royalty obligations to Merix. And some of the new improvements that are currently being tested in the clinic enable us to optimize the current ex-vivo process but also will position us for a second generation in-vivo approach that in fact is based on human embryonic stem cells which I'll return to in a few moments.

So while I will not get ahead of the investigators presentation in ASCO, let me just call your attention to some of the salient features that will be described in some detail. This is a dendritic cell based vaccine and it's actually a very sophisticated way to augment the ability of the dendritic cell to present in this case the telomerase antigen. Two patients in this case with advanced hormone refractory prostate cancer. [has the little thief imposter reposted part 1 yet?] We've studied now over 20 patients, there is a full length manuscript under review and the ASCO presentation will detail the results. In the low dose group – patients who got three weekly injections – first, all patients did respond immunologically with T cells directed against telomerase and there have been no adverse reactions. The data supporting clinical utility is really in two camps. First, of the 10 patients who had elevated levels of prostate cancer cells in their blood before the vaccine, nine of them exhibited striking clearance of those metastasizing prostate cancer cells in their bloodstream. Some of the patients as shown in these two examples with striking declines - over a thousand fold from before vaccination to after the vaccination period. Also, consistent with an in vivo effect, is significant changes in the PSA velocity. Here are three subjects in the low dose group with positive slopes before vaccination which turned negative during vaccination and for months thereafter, and after the T cells waned, the PSA slope once again becomes positive. These are all data from the low dose group.

The higher dose group is significant because of the dramatic increase in the level of telomerase T cells. This dotted line is the maximum level of T cells that we achieve in the low dose group, and here are data from two patients in the high dose group demonstrating that nearly 1 to 2 percent of their total T cell pool in the peripheral blood is telomerase specific. This has never been achieved before in the cancer vaccination, vaccination arena. These levels of specific T cells are what you see in infectious disease that result in clearance of viral particles. And as will be presented at ASCO, again no sign of treatment related side effects even in the high dose group; again, correlation with clearing circulating tumor cells; significant stabilization of PSA levels; and clear association between the course of immune responsiveness and surrogate marker effect. So we look forward to that presentation on the 6th of June.

Turning to the telomerase inhibitor program. This is a space occupying model of GRN 163 which is the prototype of our inhibitor program. This is a 13 mer oligonucleotide, a specific inhibitor of the enzyme telomerase. It has no antisense activity. This drug is active in vitro against literally all of the major tumor types in man and in 5 out of 5 animal models of human cancer. We have GLP tox studies underway, we have multiple manufacturing contracts in place, we have received GMP material, and we have issued IP protection for the chemistry that we use to build the drug, the compound itself, the target of course, and even the clinical use of the compound. We have recently made some significant advances and have chosen the, this molecule, 163L, as the compound that we are going to the clinic with. It is the same sequence and the same chemistry as 163, but with the addition of a 16 carbon palmitoyl lipid molecule to the 5 prime end of the molecule

This creates a very attractive drug in terms of its pharmacologic properties. And the simple take home message is less of 163 is better. The data are as follows. 163L is from two to 10 fold more potent in vitro at inhibiting and causing tumor cells to die in the test tube. The compound at much lower doses - 75 mics per kilo compared to 125 of 163 - is much more effective in inhibiting telomerase and in decreasing telomere length in vivo. Thirdly, in another model in liver cancer, a lower dose of 163L - 10 mics per mil - 70% reduction - is as effective as 163 in stopping tumor growth in vivo, in decreasing telomerase activity in the tumor cell in the animal or in decreasing tumor cell proliferation in biopsies of the animals. And lastly, the kinetics and degree of inhibition of telomerase for 163L are striking. So again a low dose of 163L gives us significant inhibition of telomerase activity in vivo after a single IV injection for over 7 days. So this compound will be bolus injected on day one and then injected once per week by IV injection. And the chemistry prevents complement activation so it need not be given by continuous infusion. So we, this compound has successfully met all of our design criteria for a compound with elegant, specific and powerful inhibition of telomerase with very exciting druggable properties.

Turning now to the stem cell based program for chronic disease. We've accomplished a lot in the past months. We validated that human embryonic stem cells are in fact self-renewing sources for the manufacturing of literally any cell in the body. We've learned how to make eight therapeutic cell types from our cell lines and in contrast to other cell therapy companies, we are not ever injecting undifferentiated cells. We are always injecting into the affected tissue differentiated cells that we scalably produce from the self renewing starting material. All of these eight cell types have normal in vitro function. We have learned how to scalably manufacture them much in the same way as a monoclonal antibody or a biological drug. Six of these eight therapeutic cell types are now in animal preclinical testing. We have two of our embryonic lines fully qualified for human use and our first clinical application will be spinal cord injury which I'd like to illustrate now. These cell types here for spinal cord injury are oligodendrocytes, the cells which line and wrap around or myelinate nerve cells -- we've shown these data before, they've been repeated and they are about to be published – where we demonstrate that in the control animals in red who receive under anaesthesia a permanent blow to the spine, these animals have a permanent paresis. In contrast, animals who are given the human oligodendrocytes have statistically significantly improved locomotor activity. This may not seem like very much on a graph so I would like to show you two quick movies.

First of an animal in the control group actually out here, to show you the permanent paresis the model results in and then one of the animals in the treatment group to show you the degree of response. This is a a logarithmic scale. So first the animal in the control group 9 weeks after the injury. You can see the left lower leg is nonfunctional, the animal can't control it, and its tail is dragged across the bottom of the cage. He's trying to stand on his hind legs and he's unable to do so, again, because of the injury to the spinal cord.

In contrast, here's an animal who received human cells a few weeks after the injury and the difference will be quite obvious. The tail is off the cage bottom and there's full weight bearing on both lower extremities. Now this is not the best case, this is typical of the results that we are seeing. Why are these animals improving? When we sacrifice them and look at the site of the injury, which you can see is extensive, what you see first are new neurons that are growing caudal and rostral to the site of injection of the human cells and most importantly, we see profound myelination of the rat axons which are coming out of the screen towards you by human myelin. This is an example of what this platform can do generally, actually repair - permanently - damage done, in this case, by a chronic injury.

We are also making good progress on a second cell type, cardiomyocytes. We have learned now how to scalably make these cells as well, actually following the normal in vitro differentiation pattern as, of how mother nature makes cardiomyocytes. These cells are truly ventricular cardiomyocytes, they light up with all of the appropriate markers that show them to be true human cardiomyocytes.

They have normal responses to cardiac drugs; this is critical when we put these cells into people with heart disease, those patients will be having on board cardioactive drugs and so we have to know that the cells we're adding respond to those drugs in the same way as their normal endogenous cells – and they do so. The calcium channel blockers, the alpha one and beta agonists, the phosphodiesterase inhibitors - they have normal dose response curves, showing, again, that these are normal cardiomyocytes. When we inject these first into normal animals without a heart attack, we see robust engraftment of the human cardiomyocytes that actually integrate structurally with the host myocardium. More importantly, when we inject these cells into animals that have infarctions, we restore their cardiac output. The normal cardiac output in this mouse model of a heart attack is about 30. This is done by echo. The animals in control have lost about 50% of their normal cardiac output when examined a month after the infarction. In contrast, animals that received human cells have their cardiac output restored nearly to normal. Another spectacular result again underscoring the principle generally that these are cells capable of permanently restoring tissue function that is lost, in this case, to an infarction.

We're making progress also on the third cell type, islet cells. We now have a process that makes these cells which make insulin and glucagon in appropriate dose response fashion to changing concentrations in glucose. These cells are in animal studies in Canada. We are seeing biological activity in the animal model of diabetes, but we have not yet made these cells in pure enough form to create significance in the animal data. So we have a little more work to do to clean up the preparation of these cells to make them as pure as the oligodendrocytes and the cardiomyocytes that I showed you earlier.

One other cell type we'll talk about briefly are the hematopoietic cells. These are bone marrow cells that we make from human embryonic stem cells. They are now in animal studies and there is a manuscript under review that demonstrates these cells engraft in the traditional non skid mouse, they make all the lines of blood and so they will be useful not only for bone marrow transplantation procedures, but also for one of the ways we will use to prevent graft rejection of the transplanted cells. Because we can make all of these cell types from each of our cell lines, if we give patients a low dose of these bone marrow cells from Line A, they become tolerant to any differentiated cell type from that same line. This has been demonstrated in bone marrow transplantation and solid organs transplantation in humans. This is also the cell that will be the starting material for our process to make dendritic cells which may be the scalable way to segue into the second generation dendritic cell based telomerase vaccine.

A more near term opportunity in the stem cell arena are these cells – hepatocytes, liver cells. We've demonstrated that these cells have all of the normal biology of liver cells, including inducible drug metabolizing enzymes. Therefore, these cells can be engineered with reporter genes and used for the first time by pharma to first rule out cell–drugs early in development that are toxic to the liver and perhaps more importantly to absolutely quantify the metabolic disposition of a new drug by a bona fide human liver cell that can be scaled and which is reproducible and consistent lot after lot after lot. And we expect to beta test these cells early next year.

The important point about scaleability can't be overemphasized and I illustrate the numbers here for the oligodendrocyte for spinal cord injury. Our typical master cell banks have about 200 vials of the undifferentiated stem cell in them. One vial of the undifferentiated cell in today's process makes enough glial cells for a thousand doses of patients. So therefore, if we dedicated one master bank completely to glial progenitor cells at today's efficiency, we would have enough cells for 200,000 transplants. And that would service the entire prevalence of spinal cord injury in the United States. We have now broken ground within the company for our GMP manufacturing suite for GMP master banks of the undifferentiated cells and a GMP suite for the manufacturing of these oligodendrocytes.

We mentioned that we have two lines fully qualified for human use. This is a partial list of all the tests we have subjected these two lines to and they've passed, demonstrating them at the RT-PCR level to be free of human, pig, mouse and cow viruses, therefore suitable for human use and all of our differentiated therapeutic cell types are being made from these two lines.

So the net net of the platform enables us to segue for the first time from the traditionalized individual cell therapy production method where there are more workers than patients into a closed, automated production facility where we'll be making multi dose production lots of cells for the first time.

Our IP position for these two platforms is rock solid. There are nearly 200 patent applications and issued patents on our telomerase platform, 20 issued on human embryonic stem cells, 190 pending around the world. These are good patents, they have broad claims that are not restricted and they are well exemplified. So we have the telomerase oncology and the human embryonic stem cell fields and their products that we've talked about really locked up.

So the last slide sort of gives a projected summary of where these products are in their development. So starting with oncology, the vaccine with a current indication for prostate cancer has just finished its Phase I/II clinical that will be reported at ASCO in June and we expect by next year to be in a, a Phase II clinical under a corporate IND. [Note: At the shareholders meeting he indicated Ph. II would begin at Duke to complete the ‘tweaking' of the processing before the corporate take over of the IND]

The telomerase inhibitor will be first tested in hematologic malignancies and this is because this is a non-toxic compound, so our ascending dose strategy does not have a toxic endpoint, it has a pharmacodynamic endpoint demonstrating in the tumor cell in the patient telomerase inhibition and shortening of telomere length and that's easily done with hematologic malignancies via a venipuncture. So we expect to file the IND on 163L at the end of this year and be in our Phase I/II study in hematologic malignancies early in ‘05. We expect the telomerase diagnostic for bladder cancer by Roche to be in a pivotal study early next year, and those of you who heard CellGenesys just before me, they are planning to file their IND on this telomerase promoter containing oncolytic virus by the end of this year [Note: he corrected this statement as the shareholders meeting. Not the telomerase promoter containing oncolytic virus.]

On the stem cell side, spinal cord injury will be our first clinical program and this will be in the clinic years before anyone ever predicted human embryonic stem cells therapy would be in man. We expect to file our IND in ‘05 for this indication. We are now in the process of our IND enabling studies.

The hepatocytes for drug screens will be beta tested next year, and our cardiomyocytes and our islet cells and the hematopoietic cells are currently in animal studies and we expect to put them into product development early next year.

So what you see here I think is good evidence of the successful segue of this company from a richly endowed in terms of a product portfolio into very specific product formulations that are in clinical testing or are on their way toward that as evidence of the development of value for the investment in Geron.

Thank you very much

CRX und das Roslin Institute werden ihre Expertise in den Bereichen Leberzellkultivierung sowie der Entwicklung so genannter Reportergen-Assays in die Kollaboration einbringen. Um eine chemische Reaktion ausgelöst durch einen zugesetzten Wirkstoff in einer Leberzelle nachweisen zu können wird nämlich ein so genannter Reporter benötigt. Meist ist dies ein an der Reaktion beteiligtes Enzym, das mit einem Farbstoff gekoppelt ist, welcher im Zuge der Reaktion seine Farbe ändert und damit auf den Ablauf der Reaktion hinweist. So lässt sich zeigen, welche Enzyme am Abbau von Wirkstoffen in der Leber beteiligt sind. Erfolgreich entwickelte Produkte, die die Marktreife erreichen, werden von Geron und CXR vermarktet werden, andere finanzielle Detaills wurden nicht bekannt gegeben.

Mit diesem Schritt gehen Geron und seine Partner ein seit langem bestehendes Problem in der Pharmabrache an. Bisher wurden Leberzellen zum Wirkstoffscreening aus Leichen oder aus operativ entfernten Lebern gewonnen. Allerdings ist der Bedarf sehr viel größer als die Quellen, zudem lassen sich humane Leberzellen in Zellkultur nicht vermehren, ohne dabei einen Teil ihrer Funktionalität zu verlieren. Aus den genannten Gründen greifen Medikamentenhersteller für präklinische Tests meist auf Tiermodelle zurück, welche sich aber nicht eins zu eins auf den Menschen übertragen lassen. Sollte der Geron Ansatz erfolgreich sein, würde dem in vitro Test wohl aus den genannten Gründen ein gigantisches Marktvolumen offen stehen.

What I`ll mention briefly are two programs, one the telomerase vaccine and the results from our recently completed Phase I/II study at Duke will be presented by the Duke investigators at ASCO on the 6th of June. And in that study, as you`ll see in a moment, we`ve demonstrated that this platform induces very strong and clinically efficacious anti cancer immune responses in prostate cancer and others in the academic center have demonstrated that telomerase immunization like the telomerase inhibitor drugs we`ll talk about have broad based activity against multiple tumor types because all tumors express and depend upon telomerase. I`ll talk a little bit about our telomerase inhibitor drug program. Again, we show activity of these compounds against all major human cancers in vitro and in 5 out of 5 animal models of human cancer in animals.

So to move to the vaccine quickly. In the low dose group, there are 10 of these. We had no adverse reactions and all patients responded immunologically to the vaccine. One of the striking surrogate clinical findings was in 10 of the subjects who had elevated levels of prostate cancer cells circulating in their blood before vaccination, 9 of those 10 exhibited striking declines - some of them to below detectable, over a thousand fold - loss or clearance of circulating prostate cancer cells in blood due to the vaccination process. Also some of the subjects in the low dose group exhibited striking changes in their PSA velocity, the rate at which the PSA level is increasing as the disease is progressing. So three out of three subjects here show rising PSAs before vaccination and in the immediate months after the vaccination protocol a negative slope which then returned to positivity as the immune response waned.

The high dose group was striking for the degree of immune responsiveness that we generated. And this to our knowledge has never been seen before in cancer vaccination programs. Literally one to two percent of the patients` T-cells are now specifically reactive against telomerase. That`s the kind of level we see in infectious disease vaccination strategies. So compare these levels here with the peak levels in the low dose group shown on the dotted line and the investigator on the 6th of June will talk about the high dose group in some detail, the immunologic monitoring and the impact of these elevated levels of anti telomerase T cells on PSA levels.

The second program in cancer I`ll mention today briefly is our inhibitor drug program. This is a picture of this molecule which is an oligonucleotide made of 13 building blocks that specifically and potently inhibit telomerase. This not an antisense molecule, it`s a competitive inhibitor active at the picomolar level. We`ve demonstrated the compound to be active against literally all of the major human cancers in vitro and in a wide range of human tumors in animal models. We`ve actually now developed a second generation version of this called 163L for lipid in which we hang a 16 carbon chain permanently on one end of the molecule which makes it more potent in vitro, more potent in vivo, gives it dramatically better bioavailability and much improved pharmacokinetics and we are on track to finishing our IND enabling studies with this compound and we should be in the clinic early next year. We will probably address hematologic malignancies as a first indication because this compound is also extremely nontoxic and so we need a pharmacodynamic endpoint for efficacy rather than a toxicity endpoint which would be hard to achieve with this molecule.

Turning then to the stem cell side. We`ve accomplished a lot in the past few years. We`ve learned now how to make 8 different differentiated therapeutic cell types from our undifferentiated stem cells lines. Six of them are now in animal models of disease. All of them have in fact normal in vitro function. Two of our embryonic lines are now qualified for human use, having passed all the tests asked of us by the agency to subject them to. And, interestingly, our first clinical application which we may file an IND for as early as ‘05, next year, will be in spinal cord injury and I`ll show you the reason for that. And it`s important to recognize that in contrast to most other cell therapy opportunities, this is a high margin product based cell therapy business model, not a service model because the scaleability of production of the therapeutic products is so efficient. So to give you some examples of what these cells are doing in animals, we`ll first look at the glial cells or oligodendrocytes. These are tested in an animal model of spinal cord injury in which - shown in red here - the animal under anesthesia is given a permanent lesion in the spine by a blow which results in a permanent loss of function. And I`ll show you a movie in a moment of one of the animals in the control group to show you their permanent dysfunction. In blue are the animals who received the same injury, but about a week after the injury receive a small number of human oligodendrocytes in the lesion site. And we have statistically significant improvement in the animal`s locomotion which I`ll also illustrate by a movie.

So first, here`s an animal in the control group, about out here, that demonstrates the best the animals do with spontaneous recovery. So you can see the left lower limb is paralyzed, there`s no weight bearing, the tail is being dragged across the cage, there`s the scar site from where the injury was. Animal is now trying to stand on its hind limbs which it really can`t do. This is the best the animals get. In contrast, animals that get cells show the following. Full weight bearing on both lower extremities, the tail is off the cage floor and at the very end you can see the animal can bear weight on its hind limbs, that it stands up, right about there. The reason for the improvements? When we sacrifice the animals and look at the injured site, we see first new nerves traversing the remnant of the spinal cord injury site and, shown here, human myelin wrapping around the neurons which are coming out at you from the screen. So this is an example of what these cells are doing that pills could never do - they are fundamentally re-engineering the tissue that was permanently damaged by an injury. We are showing similar results in an animal model of heart attacks where under anesthesia a mouse is given a massive heart attack and then either given a control or our human cardiomyocytes, heart muscle cells, directly injected into the size, the site of the infarct. We close the animals up, wait a month and then remeasure cardiac output by imaging and what you see is that the control animals have about a 50% loss in their cardiac output which should be about the number 30. In contrast, animals that get human cardiomyocytes directed into their heart have virtually a normal cardiac output. And the histology is similarly supportive of mechanism of improvement. The human cardiomyocytes are viable, living and functioning in the infarct site.

The third cell type are islets. We have now made from embryonic stem cells, with an inefficient process thus far, cells that make both glucagon and insulin and their insulin secretion is in appropriate dose response fashion to changing glucose concentrations. These cells are active in animal models, but as I mentioned, our manufacturing is still a little bit inefficient; we have a ways to go yet before we have a rigorous animal proof of concept.

So that gives you a flavor of what the platform can do. Our IP on both the telomerase cancer side and on the human embryonic stem side, stem cell side, really locks up the field both in terms of the actual numbers of applications or patents, but more importantly, the breadth of the claims, the absence of restrictions on the claims and the degree of exemplification in the body of the IP. And I should also mention that on the stem cell side all of the patents claim the cell types as composition of matter, not just the method to create it. So the depth of patent protection on the embryonic stem cell platform is as deep and broad as it is in the oncology side.

So the last slide, which I`ll just go through really quickly, sort of summarizes where we are in product development. So the telomerase vaccine for prostate cancer is most advanced, having just finished a Phase I/II and we expect to enter a Phase II early next year. Our telomerase inhibitor drug 163L for hematologic malignancies, we will, are finishing our IND enabling studies and plan to be in a Phase I/II hematologic malignancy early next year. The diagnostic by Roche and the oncolytic virus by Cell Genesys are under development by them. We expect both of those programs to advance in ‘05 as well.

On the stem cell side, as I mentioned, our spinal cord injury program is now in IND enabling studies and we hope to submit our IND in ‘05 for spinal cord injury. We announced today a partnership with CXR and the Roslin in the UK on our stem cell derived hepatocytes for drug screens. We expect to put these in pharma beta testing next year, and the three other cells - heart muscle, islets and hematopoetic cells - which are currently in animal studies, we expect to advance into product development experiments next year.

So thank you. That`s the quick summary of some of the examples of products in both of our major portfolios and I`d be happy to answer some questions.

Q Great. I guess first of all you`re saying for the embryonic stem cells there`s just two cell lines right now that are qualified for human use?

A What I meant to say is that we have nine lines all together and two of them are the ones that are the workhorses that we make most of the cell types for and those are the ones that we have subjected to exhaustive RTPCR testing for mouse, human, cow and pig viruses and found none. The other lines –

Q – ah –

A – simply haven`t gone through that exhaustive testing. So these are the two, and the only two that we`re aware of in the universe, that are qualified for human use.

Q And are the others going to be tested?

A Yes, we`ll do that.

Q And do you foresee regulation being a limiting factor as far as moving forward with the technology?

A Not at all, actually. These cells are unique in the world of cell therapy because the product specs that you can apply to them at the end of the process are so narrow, the manufacturing process is rigorous - the cells come out the same way each time, not because we`re clever, but because of the simple biology of the cells, that it`s inherent in them. So the regulatory pathway in terms in terms of IND enabling studies is very straightforward. It`s exactly the same kinds of studies we`re now doing in our telomerase inhibitor drugs.

Q That`s actually very interesting. And then, as far as cost of manufacturing for the cells themselves, is the main thing just the, the cell culture or –

A –that`s right. And even, that`s an important feature of the platform generally. I`ve been in the cell therapy field a long time and the rate limiting step for commercialization has always been cost of goods because all other cell therapies are basically the removal of a cell from an individual and then the workup of that batch which is then given to another individual so there`s no scale. This is like manufacturing monoclonal antibodies or a biological drug. So we make multi-dose production runs each time because of the nature of the replication capacity of the embryonic cell

Q I see. And then also in manufacturing the telomerase inhibitors, is cost a limiting factor there--

A –cost is an issue there. I didn`t mention that this is our own chemistry that we invented at Geron, it`s a thiophosphoramydate bond that`s important in terms of how the drug acts in diffusing through the body. So the good news, it`s new chemistry and it confers novel properties to an oligo. The bad news is it`s new chemistry so our contract manufacturers have to learn how to scale it up.

Q And then as far as maybe strategic partnerships, do you foresee any strategic partnerships to maybe deal with some of these costs –

A –not in the short term. I think it`s our game really to win now and we`d like to pass into the sort of Phase II and beyond stage with these programs before we start thinking even about partnering. Certainly on the stem cell side, we will not bring to the market all eight cell types, but we think we want to demonstrate to the world - medical and industrial - not only safety and efficacy on the spinal cord program and the cardiomyocytes, but also - to the point you made earlier - that these can be manufactured very efficiently to create a real margin that will be attractive to a pharmaceutical partner. So perhaps the islet cell might be the first cell type we would think about partnering.

Q Okay. And then on the same lines, can you elaborate a little bit more about the collaboration with, for the hepatocyte?

A Sure. The hepatocytes that we`ve derived thus far have Phase I and Phase II drug metabolizing enzymes and we can make them scalably and reproducibly. We could of course make them from different lines so you can imagine at some point a vocabulary of liver lines that might have unusual enzyme characteristics that represent certain populations that are at risk for hepatic toxicity. The point is we can make these scalably and reproducibly. We can genetically engineer them in the manufacturing process so we can put reporter systems in them and that`s really the subject of the collaboration between Geron, CXR Biosciences and the Roslin that we announced today. So it includes all of the product development and commercialization strategies to sell this product into the pharmaceutical industry. CXR is very well connected with a consortium of pharma in the UK, so it`s a very convenient conduit for the beta testing. This would enable, frankly, a standardized in vitro hepatocyte assay to perhaps become the gold standard for hepatocyte toxicity testing, not only to rule out drugs that are hepatotoxic but more importantly to actually define in vitro the hepatic metabolite profile of new drugs under development long before people see them because every year there`s a drug pulled off the market for unexpected liver toxicity. This system should prevent that.

Q And as far as the economics for the collaboration, can you –

A –we haven`t described– we haven`t disclosed those.

Q Okay. And I guess you, did , you didn`t really mention the nuclear transfer platform, if you could just –

A –sure. I didn`t because of time, right. We also have the IP lock on nuclear transfer that originated not in Geron but through an acquisition of Roslin Bio-Med which is a company that was spun out from Roslin, the, by the group that cloned Dolly the Sheep. And the significance of Dolly of course was she was the first animal cloned from an adult cell, and the importance to agriculture of that is that you can clone the best producing animal. You don`t, before Dolly, all animals were cloned from embryonic animal cells so you didn`t know whether that cow would turn out to be a good milk producer or a bad one. Now, you can take your adult cell from your best producer, your disease resistant strain, your best breeder and clone it. When the characteristic that`s desired is, already been expressed. So we are not doing any basic research in that field at all, it`s an outlicensing mode. We`ve licensed nine or ten companies with this technology to make it broadly available in the agricultural market.

Q And, I`m not sure if this was in house or licensed out for adenovirus as a replicator in cancer cells?

A You`re talking of the oncolytic virus?

Q Exactly.

A Yes. We published on the use of the promoter of the protein gene for telomerase as a ingredient in an oncolytic virus prep. What it means is that you, you put the promoter of telomerase just before a structural gene in the virus that the virus needs to become a virus. So the only way the virus can make itself is if it finds itself in a telomerase positive tumor cell. So the virus only replicates and kills cancer cells. We licensed that technology to Novartis and last year Cell Genesys did a deal with Novartis in which that license was transferred to them. So Cell Genesys is now developing the whole oncolytic virus program from Novartis, one of which, one or two of which products contain the telomerase promoter.

Q Okay. And is mutation a problem with the virus? Like if there is a mutation, will the virus kick out the insert or perhaps –

A –yeah. That hasn`t been seen. I think you always worry in the manufacturing of live viruses for replication competent revertence. I don`t know whether that has been or not a problem with this particular class of viruses, because, we are really not you know privy to those details. In our hands we`ve never seen that. And in our hands, frankly, what surprised us and what was the basis of the license to Novartis, was the fact that the promoter is very strong. It drives the gene vigorously and it`s not leaky. What that means is some promoters will turn on even if the appropriate signals aren`t there, and the telomerase promoter does not appear to do that.

Q And then if you can give us just a quick snapshot of financially how the company is doing.

A Yup. We have about $100 million in the bank and we are budgeting that to last us through ‘06. We have a core team of people that are focused now exclusively on product development so we have really segued from very difficult basic research you know on the telomerase biochemistry and on differentiation and derivation of embryonic stem cells to doing IND enabling studies, many of which of course we farm out. So we produce the cell and it`s sent out to collaborators to do the animal testing. On the telomerase inhibitor side, people make the drug for us and then we ship it out for IND enabling tox studies. So the composition of the company has changed quite a bit.

Q And looking towards the future as far as timelines, when do you foresee maybe the first IND application?

A Well, we went over that in the last slide. We`ve had, we will have our Phase II IND in the vaccine next year. We will have our Phase I/II on the drug we think this year. And in ‘05 the first IND for embryonic stem cells in the spinal cord injury.

Q Very nice. And with that, let`s end of session.

A Thank you very much.

Q Thank you.

***
The slide and audio presentation will be available at the following website address: www.veracast.com/webcasts/ba.../id66215434.cfm

leider geht es weiter abwärts, im momenz 7,03 dollar und das ist schon der x-te tag in folge

gruss meislo

Although designed primarily as a safety study, it was observed that patients in the high dose group experienced a statistically significant increase in their PSA doubling time during the post-vaccination period when telomerase-specific T-cells were present. PSA doubling time (the rate of increase in PSA levels, expressed as the time it would take for a patient's PSA levels to double) is a clinically used surrogate marker of disease progression. The median PSA doubling time in the high dose group before vaccination was 2.9 months. After vaccination, the median PSA doubling time improved to 100 months. Moreover, of the 10 patients who were found to have elevated levels of circulating prostate cancer cells at the onset of the study, 9 exhibited substantial reduction or complete clearance of their circulating tumor cells during the period in which telomerase specific T-cells were detected in their blood.

" These results are important," said Dr. Vieweg. " First, we are confident in the reliability of the ex vivo cell processing protocol. Second, the effectiveness of the vaccine is very high, with 19 of 20 subjects responding appropriately with the generation of telomerase-specific cytotoxic T-cells in their blood. The clinical utility of the vaccine-induced anti-telomerase immunity is reflected by the clearance of circulating prostate cancer cells from the blood and by the statistically significant prolongation of the PSA doubling time in the patients in the high dose group, which correlated with the time course of anti-telomerase immunity. We are eager to now begin the next series of studies in which patients will also receive monthly booster vaccinations in order to extend the period of telomerase immunity and to establish durable clinical effectiveness."

Significance of the Findings

The goal of therapeutic cancer vaccines is to instruct the patient's own immune system to attack cancer cells while sparing normal cells, by exposing the immune system to a substance (an antigen) that is specific to the cancer cells, thus inducing an immune response to cancer cells that present that antigen. As reported in several publications, academic groups using alternative methods to generate anti-telomerase T-cells in cancer patients have demonstrated that such cells exhibit killing activity against renal, breast, colon, lung, melanoma and hematologic cancers, consistent with the widespread expression of telomerase in all major cancer types. The Duke clinical trial uses an ex vivo (outside the body) process in which dendritic cells (the most efficient antigen-presenting cells in the body) are isolated from the patient's blood, pulsed with telomerase RNA, and then used to vaccinate the patient. With the platform used at Duke, sufficient cells can be generated from one blood draw to manufacture 12 to 15 doses of vaccine.

The new data presented yesterday show that increasing the vaccination schedule from 3 to 6 weekly injections resulted in a significant increase in the level and duration of telomerase specific cytotoxic T-cells without any apparent clinical or laboratory toxicity. The clinical effectiveness of these circulating telomerase cytotoxic T-cells was suggested by two independent surrogate markers which correlated fully with the kinetics of the induction of telomerase immunity: 1) clearance of circulating prostate cancer cells from the patient's blood and 2) significant prolongation of the PSA doubling time.

Intellectual Property

The ex vivo dendritic cell technology used in this clinical trial, developed at Duke by Dr. Vieweg and Dr. Eli Gilboa and their colleagues, was licensed by Duke to Merix Bioscience, Inc., which has supplemented it with other related technologies. Geron recently acquired from Merix co-exclusive rights to use the Merix technology in cancer vaccines using defined antigens, including telomerase. Geron holds numerous patents on telomerase and its use, including an issued U.S. patent covering the use of telomerase in an ex vivo cancer vaccine. Geron thus has exclusive rights for the use of telomerase in vaccines such as the one tested in the Duke trial.

" We are very pleased with these results, which confirm the potency and utility of the dendritic cell-based telomerase vaccine," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. " This is an extremely vigorous T-cell response for a cancer vaccine trial. These high levels of T-cell responses are comparable to those seen after vaccination for infectious diseases that result in clearance of the infection. The absence of toxicity confirms the specificity of the anti-telomerase T-cells and the selective expression of telomerase in cancer cells. The most exciting aspect of the new data is the impact of the vaccine on clearing metastasizing prostate cancer cells and on prolonging patient's PSA doubling times. Our next step is to prolong the anti-telomerase immunity by the use of intermittent vaccination booster injections. We believe that we are developing a vaccination approach that will prove to be clinically meaningful not only in prostate cancer but in other tumor types as well."

The clinical trial conducted by Duke was funded by a grant from the National Institutes of Health.

Geron is a biopharmaceutical company focused on developing and commercializing therapeutic and diagnostic products for cancer based on its telomerase technology, and cell-based therapeutics using its human embryonic stem cell technology.

This news release may contain forward-looking statements made pursuant to the " safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements in this press release regarding potential applications of Geron's technology constitute forward-looking statements involving risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, reliance on collaborators, need for additional capital, need for regulatory approvals or clearances, and the maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Geron's periodic reports, including the quarterly report on Form 10-Q for the quarter ended March 31, 2004.

Stammzellen-Bank: Ethische Konflikte um menschliche Embryos
Präsident Bush hatte im Jahr 2001 strenge Restriktionen für die Stammzellforschung verfügt. Amerikanische Wissenschaftler dürfen demnach nur noch mit 78 existierenden Stammzelllinien arbeiten. Neue Stammzellen aus Embryos zu gewinnen, untersagte Bush aus ethischen Gründen. Konservative Politiker in den USA bekämpfen die Nutzung von Stammzellen genauso wie die Abtreibung.

Angesichts des Todes von Reagan hoffen die Senatoren nun auf einen Sinneswandel beim Präsidenten. Ein Sprecher des Weißen Hauses unterstrich jedoch, dass sich Bushs Position nicht geändert habe. Der Präsident fühle sich der Stammzellforschung verpflichtet, lehne die Tötung menschlicher Embryos jedoch weiterhin ab.

Wissenschaftler hoffen, eines Tages aus Stammzellen beliebige Arten menschlichen Gewebes züchten zu können und damit Krankheiten wie Diabetes, Krebs oder Parkinson zu heilen. Gegenüber adulten Stammzellen, deren Einsatz ethisch unbedenklich ist, haben embryonale Stammzellen deutliche medizinische Vorteile. Allerdings können sie bisher nur durch die Tötung menschlicher Embryos gewonnen werden - weshalb seit Jahren ein heftiger Streit unter Wissenschaftlern, Politikern, Ethikern und Geistlichen tobt.

Deutsche Forscher glauben, eine Alternative zu den umstrittenen Stammzellen entdeckt zu haben. Sie halten die Bauchspeicheldrüse von Menschen und Ratten für eine ergiebige Quelle für Zellen, die sich ähnlich wie embryonale Stammzellen verhalten - und diese künftig ersetzen könnten



gruss meislo


Aus der pr zur asco

The median PSA doubling time in the high dose group before vaccination was 2.9 months. After vaccination, the median PSA doubling time improved to 100 months

um zu verstehen was dass bedeutet sollte man den nächsten abschnitt unbedingt lesen!!



PSA Doubling Time Indicative of Survival in Prostate Cancer Patients



According to results recently presented at the 2004 annual meeting of the American Urological Association, the time it takes for a patient’s PSA level to double is a factor in predicting survival following surgery in patients with localized prostate cancer.

Prostate cancer is the most common cancer diagnosed in men in the United States, ultimately taking the lives of nearly 30,000 men annually. The prostate is a walnut-sized gland that is located between the bladder and rectum, and is responsible for forming a portion of semen. Patients with early prostate cancer, or cancer that has not extended past the prostate, are often treated with surgery to remove the prostate and surrounding tissue, referred to as a radical prostatectomy. Although long-term survival is high following a radical prostatectomy for early-stage prostate cancer, some patients will ultimately develop disease that has spread to distant sites in the body following surgery and will die from prostate cancer. Researchers are trying to determine an association between characteristics of the cancer and/or patient and the development of advanced disease or death, so that patients at a higher risk of a cancer recurrence may be treated in a more aggressive manner to improve long-term outcomes.

Researchers from Baltimore, Maryland recently conducted a clinical study to evaluate different cancer characteristics and associated outcomes in patients with prostate cancer. This study included nearly 6,000 men who had been diagnosed with early prostate cancer and had been treated with a radical prostatectomy since 1982. Previous data from this trial indicated that the duration of time that it took for a patient’s PSA level to double was strongly associated with the progression of their cancer. Following a prostatectomy, patients who had a PSA doubling time of less than 10 months had a significantly stronger likelihood to develop advanced cancer compared to those whose PSA doubling time was less than 10 months. The researchers extended their review to evaluate associations such as PSA and treatment history and its potential effect on survival in the same group of men. At over 8 years of follow-up, the researchers discovered that PSA doubling time also effected survival in these patients. In the group of patients with a PSA doubling time of less than 10 months following a prostatectomy, 42% of patients died from prostate cancer. Conversely, in the group of patients who had a PSA doubling time of greater than 10 months, only 7% of patients died from prostate cancer.

Adding to the list of prospective therapeutic cells already produced from hESCs, Geron scientists demonstrated the differentiation of hESCs into islet-like cells similar to those found in the endocrine pancreas, which could potentially be used for the treatment of Type 1 Diabetes. The differentiated cells express the key islet hormones, insulin, glucagon, and somatostatin, as detected by both gene and protein expression analysis. The insulin-producing cells also secreted C-peptide, a cleavage product generated in islet cells during the secretion of insulin. Moreover, these differentiated cells increased their production of insulin in vitro in response to increasing concentrations of glucose, much like normal adult beta cells in pancreatic islets. "Geron is now focusing its activities on improving the purity and yields of islet cells in these differentiated hESC preparations and in transplanting these cells into animal models of Type I Diabetes," stated Greg Fisk, Ph.D. of Geron, the lead author of the presentation.

Cardiomyocytes, Oligodendrocytes and Hematopoietic Cells

Geron and its collaborators also presented data showing that cells differentiated from hESCs engraft in animal models and are functional in vivo without signs of inappropriate growth.

In studies performed by Dr. Charles Murry at the University of Washington in collaboration with Geron scientists, hESCs were differentiated into cell populations enriched in cardiomyocytes which were injected into the left ventricular wall of rats with a normal myocardium. Using probes specific for human cells, the cardiomyocytes were observed to engraft and expand during the first four weeks after transplantation, in contrast to results previously seen with primary adult rodent cardiomyocytes. At one week and four weeks after transplant, 24% and 14.4% of the cardiomyocytes, respectively, expressed Ki67, a marker of proliferating cells. Non-cardiomyocyte cells present in the original cardiomyocyte population,such as epithelial and endodermal cells, were lost over the same 4-week time period, so that at the end of the period the graft consisted entirely of cardiomyocytes. The successful engraftment of the cells, which expressed several markers of normal cardiomyocytes, provides evidence of the feasibility of using hESC derivatives in myocardial repair. Geron is currently testing these cells for their effect on cardiac function in acute and chronic infarct animal models.
An update of data from Dr. Hans Keirstead's laboratory at the University of California at Irvine showed that oligodendroglial progenitors derived from hESCs can mediate remyelination, neural sprouting and improvements in locomotor activity in rats with acute spinal cord injuries.
Dr. Mick Bhatia of the Krembil Centre for Stem Cell Biology at Robarts Research Institute in London, Ontario showed that hematopoietic progenitor cells derived from hESCs could reconstitute the hematopoietic system of immunocompromised mice. In these studies the hematopoietic progenitor cells, which expressed the surface antigens CD45 and CD34 characteristic of hematopoietic progenitor cells, were transplanted directly into the bone marrow cavity in the mouse femur. Eight weeks after transplantation, the human cells had engrafted and formed multi-lineage components of the hematopoietic system including cells of the myeloid, erythroid and lymphoid lineages.
"These studies show again that cells differentiated from hESCs can form normal human tissues in vivo," stated Jane Lebkowski, Ph.D., Geron's senior vice president of regenerative medicine. "In none of the presented studies was there evidence of uncontrolled cell growth. The studies performed in Dr. Bhatia's laboratory also support the idea that hESC-derived hematopoietic cells can establish a chimeric state in a transplant recipient that could allow acceptance of an hESC-derived therapeutic cell graft without the need for long term immunosuppression."

Derivation of New hESC Lines

Further presentations at the meeting detailed Geron's advancements in producing hESCs and their derivatives with the high standards required for therapeutic biologic products. A presentation of studies performed in collaboration with Dr. Susan Fisher of the University of California at San Francisco described two new hESC lines which were derived without exposure to mouse cells or mouse products. These new hESC lines, derived from embryos left over following fertility treatment and donated for research, were grown on human placental fibroblast feeders that were fully qualified through extensive pathogen testing, and have the same properties as the original hESC lines. Unlike the hESC lines included in the NIH Stem Cell Registry, which will be treated as "xenografts" and for which the FDA will require testing to ensure that they are free of nonhuman pathogens, these new lines have never been exposed to cells of nonhuman origin. As a result, the chance of zoonosis of murine pathogens is essentially eliminated with these new lines.

Growth of hESCs in Defined Media

In another study presented at the meeting, Geron scientists demonstrated that hESCs could be grown using serum-free medium conditioned by placental fibroblasts or other human cell strains. With adjustment of the media supplements, current and newly derived hESC lines could be grown in unconditioned serum-free medium containing only specific growth factors on purified human extracellular matrix proteins. "This defined culture system provides a much simpler system to reproducibly and more economically grow hESCs with the high quality standards required by the FDA for biologic products," stated Ram Mandalam Ph.D., Geron's senior director of product development.

"Geron is committed to developing 'off-the-shelf' hESC-based therapeutic products," stated Thomas B. Okarma Ph.D., M.D., Geron's president and chief executive officer. "The studies presented at ISSCR show that we are making substantial progress toward that goal."

gruss meislo

Die Experten vom Börsenbrief "Global Biotech Investing" empfehlen den Titel von Geron (ISIN US3741631036/ WKN 902213) zu halten.

Das Unternehmen habe erneut positive Resultate zu seiner Prostatakrebsvakzine (Impfstoff) verkündet. Nach Meinung der Wertpapierexperten könnte Geron mit dem Impfstoff einen Volltreffer gelandet haben. So würden alle bislang durchgeführten Studien beweisen, dass das Präparat die im Blut vorhandenen Krebszellen fast vollständig vernichten könne. Nebenwirkungen würden hierbei fast komplett ausbleiben.

Sollte Geron den Impfstoff in den nächsten Jahren zur Marktreife bringen, wäre das Potenzial gigantisch. So dürften allein über 1 Mrd. USD Marktpotenzial im Bereich der Behandlung von Prostatakrebs liegen. Hinzu komme, dass der Impfstoff theoretisch auch universell gegen die unterschiedlichsten Krebsarten eingesetzt werden könnte.

Die Experten vom "Global Biotech Investing" raten den Anlegern die Geron-Aktie zu halten.

Press Release Source: Geron Corporation


Geron Corporation to Present at Needham & Company Third Annual Biotechnology Conference
Tuesday June 15, 7:30 am ET


MENLO PARK, Calif.--(BUSINESS WIRE)--June 15, 2004--Geron Corporation (Nasdaq:GERN - News) will be presenting an update of the company's product development programs on Wednesday, June 16, 2004, at the Needham & Company Third Annual Biotechnology Conference in New York, New York at 3:30 pm ET.
The update of Geron's portfolio of telomerase-based anti-cancer therapies includes GRN163 and GRN163L and the ex vivo telomerase vaccine. The presentation will also include reviews of the company's human embryonic stem cell (hESC) research in spinal cord injury, diabetes and heart disease. Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer, will be giving the presentation.

The audio and slide presentation will be available at the following website address: www.wsw.com/webcast/needham8/gern/. The webcast will be archived for 30 days.

For further information, please contact Geron Corporation at 650-473-7765, or visit Needham & Company's website at www.needhamco.com.


gruss meislo

Die Chinesen geben GAS

eigentlich sollte geron die ersten sein die rückenmarkverletzungen an menschen mit stammzellen behandeln wollten nun sind die chinesen etwas zuvor gekommen. allerdings denke ich werden diese tests die die chinesen durchführen westlichenm standard nie erreichen können. diese versuche eignen sich niemals für ein zulassungsverfahren nach westlichem standard. immerhin dürfte der politische druck dadurch weiter wachsen da amerika es sich sicherlich nicht leisten will diesen wichtigen bereich der wissenschaft den asiaten zu überlassen. nicht nur china auch südkorea und japan sind in diesem bereich sehr aktiv.

geron kann heute zulegen und man spürt irgendwie dass stammzellenforschung immer mehr freunde und investoren findet. ich glaube es zeichnet sich in diesem jahr eine trendwende ab und man sollte frühzeitg investiert sein!!!!!!!!!!!!!

vielleicht verliere ich etwas neutralität auf die ich ansonsten wert lege aber insgesamt spüre ich einen ruck und will ihn auch kundtun.

gruss meislo

Briefly, this tells that certain Chinese drs are using fetal stem cells to relieve paralysis - may be crude but apparently works for some!Partial excerpt below:

" Huang is causing a stir in medical circles. Many U.S. scientists and researchers have qualms about what he's doing. But hundreds of families of paraplegics from the United States, Japan, Singapore and elsewhere are lining up to bring loved ones to Beijing for an experimental operation that may be able to help patients sit up by themselves. Or hold a cup. Or button a shirt. Or sweat below their necks.

Huang is one of a handful of researchers around the world shattering the centuries-old idea that paralysis is irreversible.

While the Bush administration sharply limits research into embryonic stem cells and fetal tissue, citing moral and ethical considerations, nations such as China are aggressively delving into such research."

Huang, a 48-year-old with an easy smile, is taking certain kinds of fetal nerve cells, culturing them and transplanting them into patients with spinal-cord injuries or other nervous-system disorders. In little more than two years, he's done the operation nearly 450 times. More than 1,000 people are on waiting lists.

Needham & Company
Third Annual Biotechnology Conference
June 16, 2004

www.wsw.com/webcast/needham8/gern/

Welcome, everybody. Our next presenting company is Geron. Presenting today is Dr. Tom Okarma, CEO of the company. Please join me, welcome Tom.

DR. OKARMA: Thanks and thank you all for coming. Today I'll be making some forward looking statements as I describe our progress in our oncology and our regenerative medicine platforms and so I call your attention to our risk factors in our SEC filings.

So let's start first with our oncology platform. Now these are products that are all based upon telomerase which remains today the world's only validated, universal and specific cancer target. Our most advanced program here in cancer is our telomerase vaccine, most recently presented at the ASCO meetings, so I can now give you a little more detail as to why we're excited by this platform. Although we're only studying it right now in prostate cancer, it's important to note that other folks in the academic world not surprisingly have shown that a telomerase vaccine is broadly active against many cancer types because all cancers express telomerase. We have acquired exclusive commercial rights for telomerase on the Merix Bioscience platform which is the platform that we're studying in the Phase I/II program that I'll describe in a few moments.

Our second major oncology plat-program is our inhibitor drug. Like the vaccine, this drug shuts down telomerase and is effective in vitro on literally all of the major forms of human cancer and in various animal studies is active in five out of five animal models of human tumors.

I won't talk much about the oncolytic virus program today or the diagnostic program. The oncolytic virus as you know is being developed by Cell Genesys under license from Geron and the diagnostic program will first be market about 12 kits for the research use only marketplace worldwide and Roche is our clinical diagnostic partner who will be developing, who is developing a test for bladder cancer and in our preliminary clinical studies we've shown this test has a positive predictive value of 84% - that means 84 out of 100 people who have telomerase in their urine also have bladder cancer. Now all of these programs as well as the target are fully protected by an ironclad intellectual property estate on telomerase and all of these products.

So let's turn first to the vaccine. We announced a few months ago that we'd acquired a license agreement with Merix Biosciences. This gives us co-exclusive rights with Merix for all defined antigens used in cancer immunotherapy and is exclusive of course for telomerase. Now this also captures Merix IP going forward for the next three years which is important in a moment as I'll explain. There are no royalty obligations to Merix, this is a fully paid up license and not only do we have the IP coverage now to optimize the ex vivo process which I'll talk about today, but the IP portfolio also enables an embryonic stem cell based second generation approach which will be much more convenient we think to manufacture.

Let's look first at the data and share with you why we're excited about this program which actually sets a new bar in the entire field of cancer vaccination. We've studied this in a Phase I/II way program in hormone refractory metastatic prostate cancer patients and the platform we're using is RNA pulsed dendritic cells. Dendritic cells are the most potent antigen presenting cell in the body and we are dosing these cells with a large dose of the RNA that codes for the whole protein telomerase. So what we're generating in vitro–in vivo rather, are hundreds, perhaps thousands of epitopes or specific portions of the telomerase antigen that enables the patient to make such a dramatic immune response against telomerase that I'll show you. So we have two dose groups – a low dose which gets 3 weekly injections and a higher dose which gets 6 weekly injections. The endpoints are of course safety and toxicity and in a word we have absolute safety – none of the patients in either cohort have had any adverse reactions and in terms of efficacy, both in terms of immune responses, circulating tumor cells and serum PSA levels, the data are very provocative. This is a busy slide, but it shows you the first point from the low dose group, all of the patients in the green bars except one responded to the vaccine, even in the low dose group. So, analyzed patient by patient, the gray bar shows no anti telomerase T cells before vaccination; the green bars show the level of T cell responses right after vaccination. So first, 11 out of 12 patients responded in the low dose group and there are absolutely no adverse reactions. Now an interesting hint of, of importance here is when we compare in the top panels patients who got a LAMP TERT which is designed to put the antigen through a different processing pathway versus patients in the lower panel that only got telomerase without LAMP, the difference is in the CD4 response. All of the LAMP patients responded with not only CD8 cells against telomerase, but also CD4 cells whereas the patients in the lower group that only got TERT did respond with CD8s, but did not have much of a CD4 response. That's critical for the quality of the CD8 cells we in fact generated. The really exciting data comes in the high dose group where we showed dramatic levels of anti telomerase CD8 T cells in all the subjects that actually approached the level we see in vaccinations for infectious disease. Not only that, in the patients receiving LAMP, we also, in green, showed significant levels of CD4 anti telomerase T cells. Now these levels are 1 to 2 percent of the total circulating cytotoxic T cell pool in these patients' bloodstreams.

That's an extraordinarily high level of specific antigen responsive T cells, and again, like in the no dose–low dose group, absolutely no adverse reactions. In terms of efficacy, first, 9 out of 10 patients, 10 of whom had elevated levels of circulating prostate cancer cells in blood before vaccination, 9 of them either reduced or completely cleared their circulating tumor cells during the period of time that we had anti telomerase T cells present. That's shown in the two upper graphs here, for two of the subjects. Perhaps more significantly to this audience is the impact of the vaccination on PSA doubling time, an accepted clinical surrogate marker of tumor progression. We saw no impact in the low dose group, but a highly statistically significant increase in the PSA doubling time in the patients in the high dose group. These patients essentially had stable disease as long as they had anti telomerase T cells in their blood. That's important. The correlation between the time course of anti telomerase T cells and these clinical effects implies causality. So our next step is to extend the vaccination protocol by giving patients monthly boosts to increase the duration of the T cell response and hopefully thereby create a durable clinical effect.

Turning now to the telomerase inhibitor drugs. The parent molecule was called GRN163. This is a 13 mer oligonucleotide that specifically inhibits the enzyme telomerase - it is not antisense. It shuts down the enzyme specifically in the cancer cell. The chemistry that we used to build this drug was invented by a Geron employee. It increases the stability of the compound in plasma and creates an extraordinarily tight bond between the drug and the active site. We've shown in vitro evidence that this drug inhibits telomerase in every single form of major human cancer and in vivo in animal models in 5 out of 5 models of human tumors. Our IP fully protects the compound, the chemistry we use to build it, of course the telomerase target, and even clinical use. The second generation compound, the one that we will be filing our IND on at the end of this year, is called GRN163L; it's an improvement because we add a covalently bound lipid molecule to one end of the sequence. This makes an enormous difference as you'll see in the next few slides.

First, when we compare the two drugs in vitro, there's a 2 to 10 fold increased potency of 163L compared to 163 in inhibiting telomerase and shutting down tumor cells in vitro. That occurs in the test tube. When we look in vivo, less of 163, 75 milligrams per kilo per week compared to 125 mgs per kilo per week gives us much better inhibition of telomerase activity in the tumor cell and a much more dramatic shortening of telomere length. So less is better of 163L. That's also true if we measure tumor growth. So here if you compare the red and the green bars, we're looking at a high dose of 163, a 70% reduced dose of 163L, and they are equivalent in terms of reducing tumor growth, shutting down telomerase activity, stopping tumor cells from proliferating. And lastly, in terms of pharmacokinetics, again, a much reduced dose of 163L gives significant telomerase inhibition for at least 7 days after a single IV dose in the animal. So our next steps are to complete the IND enabling studies with 163L and file our IND at the end of this year for hematologic malignancies.

Turning now to our stem cell programs. We've accomplished a lot in a relatively short time since these cells have been derived. In short, we have validated the unique utility of human embryonic stem cells as a self renewing source for the scalable manufacturing of replacement cells for literally any organ in the body. We've learned how to make 8 different therapeutic cell types, differentiated cells that we can scalably produce from our human embryonic stem cell lines. All of them have normal in vitro function; 6 of them are now in animal models of disease in preclinical testing. We know how to scalably manufacture these cells and I'll come back to that point in a few moments. We have two embryonic lines fully qualified for human use – that means these therapeutic cells we make from them can go directly into human clinical trials.

Our first clinical trial will be in spinal cord injury, the glial cell, that I'll describe in a moment. And what's important about the scaleability and the manufacturing efficiency is that those facts enable a high margin, product based cell therapy business model as opposed to a service model such as in a blood bank or in bone marrow transplantation and, like telomerase, we have a controlling intellectual property estate that not only covers methods to derive the cells and produce them, but it covers the therapeutic cell types as composition of matter.

So let's first turn to the most advanced cell type, the oligodendrocyte or glial cell. These are designed first for spinal cord injury, and these data show in graphic form what these cells do to an animal model of spinal cord injury. First, in red, is the control group. The animals that get the injury - and the, you can see after more than 3 weeks they have a permanent loss of function, and I'll show you a movie in a moment that illustrates how dysfunctional these animals are. In contrast, in blue, animals that receive, right about here, about a week after the injury, a small dose of human glial cells, have a statistically significant improvement in their locomotor function. Pictures tell a thousand words, so first I'm going to show you one of the animals in the control group that's actually way out here, at about 8 or 9 weeks, and then I'll show you a quick clip of one of the animals in the treatment group so you can see for yourself the difference in their function. Will the movie work? Well, of course not, we can't do that. Okay, well, I, oh I can tell you what the movie shows. The animals in the control group have virtually complete loss of their lower legs and they drag their tail around the cage, and most of them have lost bladder function. Animals that receive cells support their weight on all four limbs and their tail is held erect. It's a dramatic response visually. But more important than the visuals or the graphics is when we ask the question well, why did this work. So we sacrifice the treated animals and look histology into the lesion to ask what happened. And here is the results. First, here is the injury. [I see the lil thief imposter is out already. Haven't seen him in awhile] It's a large hole in the spine, the spinal cord. Under high power this portion of the intact cord which is in the area of the injection of the cells, shows new rat axonal growth produced by the trophic factors the glial cells produce. Secondly, now the axons are coming out of the screen at you in cross section, what you see here is human myelin that is surrounding or insulating the rat's axons coming out to you. So what this does is show the potential of this platform generally, to do what drugs could never do, to functionally restore and recreate the normal architecture of tissue in this case permanently damaged by an injury. And in the next example, cardia–myocardial infarction, a tissue loss produced by an acute event. So let's turn to cardiomyocytes.

We've learned how to make these elegantly and they have all of the appropriate markers that prove them to be human cardiac muscle, not a proxy. Second, these drug–these cells respond normally to cardiac drugs which is important because we're going to be putting these cells into patients with heart attacks who will be taking cardiac drugs. So the new cells have to respond to cardiac drugs the same way as the patient's own cells. And these data show that they do. When we engraft them into animals we show robust engraftment of healthy human cardiomyocytes. They make myosin, they make all of the connections that enable them to integrate structurally with the animal's heart tissue. Most importantly, what about function? These are mice that are given a massive heart attack and either treated with controls, saline injections, or the human cardiomyocytes, sewn up and then measured for cardiac output a we–a month later. What you see in the controls is a 40% loss in cardiac output. This would be a severe class four human cardiac patient. In contrast, animals that get the human cardiomyocytes have cardiac output restored virtually to normal. And the histology is the same as what we saw in the spinal cord injury – clear histologic evidence of engraftment that is causing the functional recovery. Another general illustration of what this platform promises.

Thirdly, we've learned now how to make insulin producing islet cells. We've not yet learned how to scale this cell, although we are in animal studies and we're seeing animal biological activity, but still the fraction of cells that express insulin is too low for our standards. Nevertheless, these cells do secrete insulin in an appropriate dose response fashion to glucose, like your islets and like mine

We've learned how to make these elegantly and they have all of the appropriate markers that prove them to be human cardiac muscle, not a proxy. Second, these drug–these cells respond normally to cardiac drugs which is important because we're going to be putting these cells into patients with heart attacks who will be taking cardiac drugs. So the new cells have to respond to cardiac drugs the same way as the patient's own cells. And these data show that they do. When we engraft them into animals we show robust engraftment of healthy human cardiomyocytes. They make myosin, they make all of the connections that enable them to integrate structurally with the animal's heart tissue. Most importantly, what about function? These are mice that are given a massive heart attack and either treated with controls, saline injections, or the human cardiomyocytes, sewn up and then measured for cardiac output a we–a month later. What you see in the controls is a 40% loss in cardiac output. This would be a severe class four human cardiac patient. In contrast, animals that get the human cardiomyocytes have cardiac output restored virtually to normal. And the histology is the same as what we saw in the spinal cord injury – clear histologic evidence of engraftment that is causing the functional recovery. Another general illustration of what this platform promises.

Thirdly, we've learned now how to make insulin producing islet cells. We've not yet learned how to scale this cell, although we are in animal studies and we're seeing animal biological activity, but still the fraction of cells that express insulin is too low for our standards. Nevertheless, these cells do secrete insulin in an appropriate dose response fashion to glucose, like your islets and like mine.





So lastly, I'm almost out of time, I'd like to give a little bit of sense of progress and of what to look forward to as these programs mature.

So on the oncology side, the telomerase vaccine which has currently finished its Phase I/II study at Duke in prostate cancer, we expect to move into a Phase II clinical in ‘05 and the Phase II as I mentioned will extend the vaccinations to prolong the period of T cell reactivity and thereby hopefully make a durable clinical response and it will also incorporate some improvements that are currently being tested at Duke to reduce the burden of manufacturing and to increase the potency of the vaccine – improvements all of which came with our Merix license. 163L will - we hope to file our IND at the end of this year for hematological malignancies. Why those tumors? Because we have a compound that's pretty nontoxic and what we want to demonstrate in the tumor cell is loss of telomerase activity and telomere shortening and hematologic malignancies are of course available for that testing via a venipuncture. Once we demonstrate safety and activity of that compound in hematologic malignancies, we will spread to other tumor types, again, because of the ubiquity of telomerase.

The diagnostic under development by Roche should go into beta testing in ‘05, and we hope that Cell Genesys will put the oncolytic virus into an IND next year. [Guess the lil thief couldn't put the last of it together]

On the stem cell side, we are in our IND enabling studies for the first clinical trial in spinal cord injury. We have a GMP operation at the company. We're now building our GMP master cell bank for this program. So we expect an IND submission in ‘05. That's years before most people expected this platform to ever see human clinical testing.

The hepatocytes for drug screens we expect to beta test in pharma next year and the three other cell types we mentioned briefly: cardiomyocytes, islets and hematopoietic cells which are currently in animal studies should advance into product development next year as well.

So that's the product portfolio timeline. The progress that we've made in the clinic with the telomerase based products that promise to be broadly active across all forms of human cancer, and our progress on the embryonic stem cell platform which promises to go beyond the reach of pharmaceuticals by fundamentally correcting the basic cause of chronic disease, which is tissue loss.

Thank you very much. Our breakout's across the hall


gruss meislo

wer wissen will, wie bush`s chancen auf wiederwahl stehen, kann einen blick auf eine börse werfen, wo auch politische kontrakte gehandelt werden:

www.intrade.com/jsp/intrade/contractSearch/...082384&grpID=70#

bush`s chancen stehen bei ca. 58% (siehe vorletzter kontrakt am ende)



sollte bush die wahl am 2. november verlieren, werden stammzellenaktien die profiteure von dieser möglichen abwahl sein.


gruss meislo

gegen Bus


Kerry Pledges to Once Again Make America the Leader in Science; 48 Nobel Prize Winning Scientists Endorse Kerry for President

6/21/2004 9:48:00 AM


--------------------------------------------------

To: National Desk, Political Reporter

Contact: Allison Dobson of John Kerry for President, 202-464-2800, Web site: www.johnkerry.com

DENVER, June 21 /U.S. Newswire/ -- Kicking off a week focused on his plan to make the American economy stronger at home through scientific discovery, technology and innovation, Democratic Presidential candidate John Kerry today pledged to lift up families and create new jobs by once again making America the world leader in science. While the Bush administration has politicized science, Kerry will put America back on the path of scientific excellence with a commitment to scientific research based on fact -- not ideology.

Kerry was also endorsed in a letter Monday by 48 Nobel Prize winning scientists. The scientists issued a letter calling Kerry a "clear choice for America's next President" who will "restore science to its appropriate place in government and bring it back into the White House." (Text of the Letter and List of Scientists Below)

With American families struggling in an economy that has failed to lift them up, scientific discovery has the potential to make us stronger at home by lowering health care costs, developing new technologies that will create good paying jobs and curing disease. However, to realize this potential and strengthen our country, Kerry stressed today that we need a President committed to science and encouraging innovation.

"The American people deserve a President who understands that when America invests in science and technology and higher education, we can build a new and stronger economy for the 21st century," Kerry said.

For three years, the Bush administration has squandered America's leadership in the world, putting politics before science and doing nothing to create jobs while our workers fall further behind. The administration has proposed cuts for scientific research and grossly distorted and politicized science on issues from mercury pollution to stem cell research. This approach not only limits the research that our scientists are doing today, it undermines important discoveries of tomorrow and threatens America's critical edge in innovation.

Kerry's plan will reverse this course by restoring America's scientific leadership, helping find new cures, cutting health care costs and developing new technologies that will create good jobs.

The Kerry plan begins by embracing America's tradition of looking forward. It is important to keep America's edge on science and technology to assure America is economically competitive. Kerry will invest in our nation's scientific research with the aim of making new discoveries to help cure diseases and keep America's economy on the cutting edge.

"We need a president who will once again embrace our tradition of looking toward the future and new discoveries with hope based on scientific facts, not fear," Kerry said.

Second, Kerry will embrace empirical science based on facts, not ideology. He will turn to our nation's scientific leaders and make decisions based on expert advice.

As president, Kerry will also overturn the ban on federal funding of research on new stem cell lines, and he will allow doctors and scientists to explore their full potential with the appropriate ethical oversight.

"If we pursue the limitless potential of our science -- and trust that we can use it wisely -- we will save millions of lives and earn the gratitude of future generations," Kerry said. "We have the potential to do so much good while at the same time meeting some very practical challengeslowering health care costs and creating new jobs. It's about investing in the future of our country. I won't let ideology and fear stand in our way."

In the coming days, Kerry will continue to lay out his plan to make us stronger at home through science, technology and innovation, including investing in new technologies and preparing our workforce for the jobs of the future.

---

Following is the text of a letter from Nobel Prize winning scientists, endorsing John Kerry for President:

ENDORSEMENT LETTER

An Open Letter to the American People

June 21, 2004

Presidential elections present us with choices about our nation's future. We support John Kerry for President and urge you to join us.

The prosperity, health, environment, and security of Americans depend on Presidential leadership to sustain our vibrant science and technology; to encourage education at home and attract talented scientists and engineers from abroad; and to nurture a business environment that transforms new knowledge into new opportunities for creating quality jobs and reaching shared goals.

President Bush and his administration are compromising our future on each of these counts. By reducing funding for scientific research, they are undermining the foundation of America's future. By setting unwarranted restrictions on stem cell research, they are impeding medical advances. By employing inappropriate immigration practices, they are turning critical scientific talent away from our shores. And by ignoring scientific consensus on critical issues such as global warming, they are threatening the earth's future. Unlike previous administrations, Republican and Democratic alike, the Bush administration has ignored unbiased scientific advice in the policy-making that is so important to our collective welfare.

John Kerry will change all this. He will support strong investments in science and technology as he restores fiscal responsibility. He will stimulate the development and deployment of technologies to meet our economic, energy, environmental, health, and security needs. He will recreate an America that provides opportunity to all at home or abroad who can help us make progress together.

John Kerry will restore science to its appropriate place in government and bring it back into the White House. He is the clear choice for America's next President.

Signed,

Peter Agre, Chemistry, 2003

David H. Hubel, Medicine, 1981

Sidney Altman, Chemistry, 1989

Louis Ignarro, Medicine, 1998

Philip W. Anderson, Physics, 1977

Eric Kandel, Medicine, 2000

David Baltimore, Medicine, 1975

Walter Kohn, Chemistry, 1998

Baruj Benacerraf, Medicine, 1980

Arthur Kornberg, Medicine, 1959

Paul Berg, Chemistry, 1980

Leon M. Lederman, Physics, 1988

Hans A. Bethe, Physics, 1967

T. D. Lee, Physics, 1957

Gunter Blobel, Medicine, 1999

David M. Lee, Physics, 1996

N. Bloembergen, Physics, 1981

William N. Lipscomb, Chemistry, 1976

Leon N. Cooper, Physics, 1972

Roderick MacKinnon, Chemistry, 2003

James W. Cronin, Physics, 1980

Mario J. Molina, Chemistry, 1995

Johann Deisenhofer, Chemistry, 1988

Joseph E. Murray, Medicine, 1990

John B. Fenn, Chemistry, 2002

Douglas D. Osheroff, Physics, 1996

Val Fitch, Physics, 1980

George Palade, Medicine, 1974

Jerome I. Friedman, Physics, 1990

Arno Penzias, Physics, 1978

Walter Gilbert, Chemistry, 1980

Martin L. Perl, Physics, 1995

Alfred G. Gilman, Medicine, 1994

Norman F. Ramsey, Physics, 1989

Donald A. Glaser, Physics, 1960

Burton Richter, Physics, 1976

Sheldon L. Glashow, Physics, 1979

Joseph H. Taylor, Physics, 1993

Joseph Goldstein, Medicine, 1985

E. Donnall Thomas, Medicine, 1990

Roger Guillemin, Medicine, 1977

Charles H. Townes, Physics, 1964

Dudley Herschbach, Chemistry, 1986

Harold Varmus, Medicine, 1989

Roald Hoffmann, Chemistry, 1981

Eric Wieschaus, Medicine, 1995

H. Robert Horvitz, Medicine, 2002

Robert W. Wilson, Physics, 1978

The views of expressed in this letter represent those of the signers acting as individual citizens. They do not necessarily represent the views of the institutions with which they are affiliated.

---

Paid for by John Kerry for President, Inc.


www.usnewswire.com/

Am 28. April 2004 hatte die Kirin Brewery Co., Ltd., eine Klage gegen Geron beim U.S. Bezirksgericht für Nordkalifornien eingereicht. In der Klageschrift wurde behauptet, der Erwerb bestimmter Rechte von Merix Bioscience durch die Geron Corporation würde mit den Rechten von Kirin interferieren und das Geschäft der Japaner negativ beeinträchtigen. Geron hatte kurz zuvor von Merix Bioscience Rechte zur Entwicklung von Krebsimpfstoffen erworben, welche Geron nach gütlicher Einigung mit Kirin nun weiterhin nutzen darf.

Damit ist die Unsicherheit im Hinblick auf den Ausgang eines Prozesses auch von der Geron-Aktie genommen, die seit dem Bekannt werden der Klage keine deutliche Richtung mehr einnehmen konnte. Geron will nämlich nicht mehr nur Stammzellenforschung betreiben, sondern endlich auch therapeutische und diagnostische Produkte entwickeln, die sich etwas schneller als die noch umstrittene Stammzellentherapie einer Vermarktung zugänglich machen lassen. Mit dem Erwerb bestimmter Rechte von Metrix Bioscience hat es Geron auf die Erfolg versprechenden therapeutischen Vakzinen abgesehen, die dendritische Zellen von Patienten nutzen um damit maßgeschneiderte Impfstoffe herzustellen.

Bei Dendreon (NasdaqNDN; WKN:615606) hat dieser Ansatz sich bereits als erfolgreich erwiesen. Schon zwei Krebsimpfstoffe basierend auf dieser Technologie, konnte Dendreon in fortgeschrittene Stadien der klinischen Entwicklung bringen. Mit der Beilegung des Rechtsstreites hat nun auch Geron die Möglichkeit zur Entwicklung eines entsprechenden Produktes.

Geron Announces Publication of Data on GRN163, a Telomerase Inhibitor, in Animal Models of Human Brain Tumors
Thursday July 1, 7:30 am ET


MENLO PARK, Calif.--(BUSINESS WIRE)--July 1, 2004--Geron Corporation (Nasdaq:GERN - News) announced today the publication of preclinical testing of GRN163, its first-generation telomerase inhibitor drug, in models of human glioblastoma, one of the deadliest forms of brain cancer. The results indicate that GRN163 can prevent or suppress the growth of human glioblastoma tumor cells in mice and rats. In addition, the data suggest that intracranial injection of GRN163 achieves robust distribution of the compound in the brain. The paper, authored by scientists at Geron and the Brain Tumor Research Center and Department of Pathology, University of California, San Francisco, appears in the July 2004 issue of the journal Neuro-Oncology and is available online at neuro-oncology.mc.duke.edu.
In three independent studies of athymic (immune-compromised) mice, human malignant glioblastoma cells were implanted under the skin of the flank, and allowed to grow to various sizes. The resulting tumors were then treated with injections of GRN163 plus a lipid carrier. In each study, after short-term treatment (7-19 days) with GRN163, average tumor size was significantly reduced in the treated versus control mice, and the survival of treated mice was significantly increased (p less than 0.01). In some cases, tumor growth in the treated mice was essentially blocked and in one case, the tumor completely disappeared.

GRN163 was also tested in an intracranial model of human glioblastoma in athymic rats. In these studies, GRN163 was tested without the lipid carrier, as it was first established that GRN163 alone could penetrate brain cells and would widely distribute itself within the hemisphere of the brain into which it was injected. In the distribution study, GRN163 was labeled with a fluorescent tag, infused by pump into the rat brain over a period of seven days and found to persist without diminution for at least four days after infusion (the longest time-point studied).

Two types of efficacy studies were then conducted in rats. In the first study, designed to mimic a model of minimal residual disease or tumor prevention, human glioblastoma tumor cells were injected into the rat brain, and beginning 1-2 hours thereafter, GRN163 was infused into the same site over a 7- or 14-day period. Five out of seven rats treated with GRN163 showed no neurological signs of tumor progression and were found to have no evidence of brain tumors at the end of the study (day 103). They were considered cured. In contrast, all four control rats required euthanasia between days 41 and 43, and were found to have large brain tumors at the site of cell injection.

In the second intracranial (within the brain) rat model, designed to mimic a typical therapeutic efficacy study, tumors were implanted into 20 rats and allowed to become established for 14 days before GRN163 or a control oligonucleotide was infused over a 7-day period into the implantation site. The control animals had a median survival of 37.5 days (range 37-43), while the low- and high-dose GRN163 animals had median survivals of 45 and 54 days, respectively, with two of the eight animals (25%) in each of the GRN163 groups being cured -- i.e., they showed no signs of a tumor and no signs of any neurological symptoms at day 94 when they were sacrificed. The increased survival of GRN163-treated animals over the control group was statistically significant at both doses.

"These rodent studies suggest that GRN163 might prove effective for the treatment of human brain tumors, as well as the prevention of relapse following surgical removal of tumors," stated Dennis Deen, Ph.D., senior author of the paper and Professor of Neurological Surgery in the Brain Cancer Research Center at UCSF.

"We believe that GRN163 or our improved second-generation compound, GRN163L, will be useful in the treatment of brain cancer," stated Calvin Harley, Ph.D., Geron's chief scientific officer. "We are currently focused on the development of GRN163L, our lipid-conjugated analog of GRN163, for the systemic (whole body) treatment of hematologic tumors in order to establish safety and pharmacological activity. However, we are optimistic that we can move into multiple solid tumor trials, including brain cancer, after demonstrating positive clinical results with hematologic tumors."

Geron has broad proprietary rights covering GRN163, GRN163L and the platform technologies underpinning this approach to treating cancer through telomerase inhibition. For example, Geron holds issued U.S. and overseas patents to the sequence of the hTR molecule and oligonucleotides derived from hTR, including GRN163 and GRN163L, and the uses of such oligonucleotides to inhibit telomerase. Geron also owns patents and patent applications covering oligonucleotides with phosphoramidate backbone linkages and methods of synthesizing such oligonucleotides. More broadly, Geron has over 180 issued patents worldwide on various aspects of telomere biology, telomerase and telomerase inhibition and oligonucleotide chemistry, and more than 95 pending patent applications.

Geron is a biopharmaceutical company focused on developing and commercializing therapeutic and diagnostic products for cancer based on its telomerase technology, and cell-based therapeutics using its human embryonic stem cell technology



gruss meislo

Geron verkündet Publikation von Daten auf GRN163, Telomerase Hemmnis, in Tier Modelle von menschlich Gehirn Tumoren Donnerstag Juli 1, 7:30 morgens UND MENLO PARK, Calif. -- (BUSINESS WIRE) -- Juli 1, 2004 -- Geron Corporation (Nasdaq:GERN - Nachrichten) verkündete heute die Publikation der preclinical Prüfung von GRN163, seine Erste-Generationstelomerasehemmnisdroge, in den Modellen menschlichen glioblastoma, eine der tödlichsten Formen des Gehirnkrebses.  Die Resultate zeigen an, daß GRN163 das Wachstum der menschlichen glioblastomatumorzellen in den Mäusen und in den Ratten verhindern oder unterdrücken kann.  Zusätzlich schlagen die Daten vor, daß intracranial Einspritzung von GRN163 robuste Verteilung des Mittels im Gehirn erzielt.  Das Papier, geschrieben von den Wissenschaftlern an Geron und am Gehirntumorforschungszentrum und an der Abteilung der Pathologie, Universität von Kalifornien, San Francisco, sieht in der Ausgabe Julis 2004 der JournalNeuro-Onkologie und ist online an neuro-oncology.mc.duke.edu vorhanden aus.  In drei unabhängigen Studien der athymic (immun-verglichenen) Mäuse, wurden menschliche bösartige glioblastomazellen unter der Haut der Flanke eingepflanzt und gelassen sich zu verschiedene Größen entwickeln.  Die resultierenden Tumoren wurden dann mit Einspritzungen von GRN163 plus eine Lipidfördermaschine behandelt.  In jeder Studie nach kurzfristiger Behandlung (7-19 Tage) mit GRN163, wurde durchschnittliche Tumorgröße erheblich in behandelt gegen Steuermäuse verringert, und das Überleben der behandelten Mäuse wurde erheblich erhöht (p weniger als 0,01).  In einigen Fällen wurde Tumorwachstum in den behandelten Mäusen im Wesentlichen blockiert und in einem Fall, verschwand der Tumor vollständig.  GRN163 wurde auch in einem intracranial Modell des menschlichen glioblastoma in den athymic Ratten geprüft.  In diesen Studien wurde GRN163 ohne die Lipidfördermaschine geprüft, da es zuerst hergestellt wurde, daß GRN163 alleine Gehirnzellen eindringen könnte und sich weit innerhalb der Hemisphäre des Gehirns verteilen würde, in das sie eingespritzt wurde.  In der Verteilungsstudie wurde GRN163 mit einem Leuchtstoffumbau beschriftet, hineingegossen durch Pumpe in das Rattegehirn über eine Zeitdauer von sieben Tagen und gefunden, um ohne Verminderung für mindestens vier Tage nach Infusion (der längste Zeit-Punkt studiert) fortzubestehen.  Zwei Arten Wirksamkeitstudien wurden dann in Ratten geleitet.  In der ersten Studie entworfen, um ein Modell der minimalen Restkrankheit- oder Tumorverhinderung nachzuahmen, wurden menschliche glioblastomatumorzellen in das Rattegehirn eingespritzt, und danach anfangend 1-2 Stunden, wurde GRN163 in den gleichen Aufstellungsort über eine Periode 7 oder 14-day hineingegossen.  Fünf aus sieben Ratten heraus behandelten mit GRN163 zeigten keine neurologischen Zeichen der Tumorweiterentwicklung und wurden gefunden, um keinen Beweis der Gehirntumoren am Ende der Studie (Tag 103) zu haben.  Ihnen galten als kuriert.  Demgegenüber erforderten alle vier Steuerratten euthanasia zwischen Tagen 41 und 43 und wurden gefunden, um große Gehirntumoren am Aufstellungsort der Zelleneinspritzung zu haben.  Im zweiten intracranial (innerhalb des Gehirns) Rattemodell entworfen, um eine typische therapeutische Wirksamkeitstudie, Tumoren nachzuahmen wurden in 20 Ratten eingepflanzt und gelassen hergestellt für werden, 14 Tage bevor GRN163 oder ein Steueroligonucleotide über einen 7tägigen Zeitraum in den Einpflanzungaufstellungsort hineingegossen wurden.  Die Steuertiere hatten ein mittleres Überleben von 37,5 Tagen (Strecke 37-43), während die Tief und Tiere der Hochdosis GRN163 mittleres Überleben von 45 und 54 Tagen beziehungsweise mit zwei der acht Tiere (25%) in jeder der Gruppen GRN163 hatten, die kuriert wurden -- d.h., sie zeigten keine Zeichen eines Tumors und keine Zeichen aller neurologischen Symptome an Tag 94, als sie geopfert wurden.  Das erhöhte Überleben der GRN163-treatedtiere über der Steuergruppe war- statistisch an beiden Dosen bedeutend.  "diese Nagetierstudien vorschlagen, daß GRN163 wirkungsvolles für die Behandlung der menschlichen Gehirntumoren prüfen konnte, sowie die Verhinderung des Rückfalls chirurgischem Abbau der Tumoren," angegebenes Dennis Deen, Ph.D., älterer Autor des Papiers und Professor der neurologischen Chirurgie in der Gehirnkrebsforschungmitte an UCSF folgend.  "wir glauben, daß GRN163 oder unser verbessertes der zweiten Generationmittel, GRN163L, in der Behandlung des Gehirnkrebses nützlich sind," angegebenem Calvin Harley, Ph.D., Gerons wissenschaftlicher hauptsächlichoffizier.  "wir werden z.Z. auf die Entwicklung von GRN163L, von unserer Lipid-konjugierten Entsprechung von GRN163, denn von Körper Behandlung (des vollständigen Körpers) der hämatologischen Tumoren gerichtet, um Sicherheit und pharmakologische Tätigkeit herzustellen.  Jedoch sind wir optimistisch, daß wir in mehrfache feste Tumorversuche, einschließlich des Gehirnkrebses umziehen können, nachdem wir demonstriert haben positive klinische Resultate mit hämatologischen Tumoren.",  Geron hat ausgedehnte eigene Rechte, GRN163, GRN163L und die Plattformtechnologien zu umfassen, die diese Annäherung zum Behandeln des Krebses durch telomerasehemmung untermauern.  Z.B. gaben Einflüsse Geron VEREINIGTE STAATEN und Überseepatente zur Reihenfolge des hTRmoleküls und -Oligonucleotides, die vom hTR, einschließlich GRN163 und GRN163L abgeleitet wurden, und den Gebrauch solcher Oligonucleotides heraus, telomerase zu hemmen.  Geron besitzt auch die Patente und Patentanfragen, die Oligonucleotides mit phosphoramidaterückgratsgestänge und Methoden des Synthetisierens solcher Oligonucleotides bedecken.  Breit, hat Geron über 180 herausgegebenen Patenten weltweit auf verschiedenen Aspekten der telomerebiologie, des telomerase und der telomerasehemmung und des -Oligonucleotide Chemie und mehr als 95 während Patentanfragen.  Geron ist eine biopharmaceutical Firma, die auf das Entwickeln und die Kommerzialisierung der therapeutischen und Diagnoseprodukte für den Krebs gerichtet werden, der auf seiner telomerasetechnologie basiert, und auf Zellenbasistherapeutik mit seiner menschlichen embryonalen Stammzelletechnologie

Moreover, transplanted undifferentiated hESCs were found to actively inhibit certain immune responses. Injection of hESCs into mice along with endotoxin, a strong stimulator of inflammation, did not produce the inflammatory granulocyte and lymphocyte infiltration that resulted from injection of endotoxin alone or endotoxin along with another type of human cell.

These observations were supported by in vitro studies showing that the undifferentiated hESCs could actively inhibit the potent T-cell responses that normally occur when human peripheral blood cells from two individuals are co-cultured. This inhibitory effect was found to be an intrinsic property of the hESCs themselves, and was not caused by some factor secreted by the hESCs.

"This work has major implications for hESC-based transplantation therapies," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "The studies indicate that undifferentiated hESCs can locally prevent immune rejection responses, while neither undifferentiated nor partially differentiated hESCs cause typical immune rejection responses. This may mean that undifferentiated hESCs, irradiated to prevent their proliferation, can be used to protect grafts of cells differentiated from hESCs. We are conducting further studies to determine if these immune-privileged properties are retained by more fully differentiated hESC-derived cells. In either case, it may be possible that hESC-derived grafts may require reduced or no immunosuppression."

Die Aktie gehört nach langer verlustphase heute mal zu den topperformern
immerhin 11% und die markttechnik sieht auch nicht mehr ganz so wild aus.

gruss meislo

We upset a lot of people," said Dr. Gabriel Nistor, who was the first researcher to join Keirstead's lab five years ago. " No one believed us at first." Keirstead and Nistor were stars at the same gathering in October, and their research will be published next month in a scientific journal.

Kierstead is as close as anyone in the stem cell research world could be to celebrity, and reporters have beaten a well-worn path to Keirstead's lab. The fact that he's wealthy only adds to his growing luster.

Keirstead recently sold a biotech company he co-founded, unrelated to his stem cell work, in a deal that could be worth as much as $8 million.

" We all love Hans - for various reasons," said Karen Miner, whose advocacy organization helps fund Keirstead's work.

Miner and her colleagues at Research for Cure, based in Escalon in California's Central Valley, have contributed $170,000 over the last four years to the Reeve-Irvine Research Center where Keirstead works. The center is named for its founding donor, actor Christopher Reeve, who died in October of complications related to his paralysis.













SG Cowan 5th Annual Global Health Care Conference 2004
The Hilton, Geneva, Switzerland November 16-17th 2004
//www.talkpoint.com/viewer/starthere.asp?pres=108232

Okay. Good afternoon. I want to thank everyone for sticking it out toward the end of the day here. I think you'll be well rewarded with a very interesting presentation from our next company, Geron, who's front and center and certainly leading the charge in a couple of very exciting areas of science - stem cell research and telomerase inhibition and it's, in fact it's on cancer. So it's my pleasure to turn it over to the company's chief executive officer, Tom Okarma. Tom.

DR. OKARMA: Thanks Eric, and thank you for coming today. Like everyone else, I'll be making some forward looking statements so we call your attention to our risk factors in our SEC filings.[Slide 2]

[Slide 3] Let's start with who we are and sort of what the game plan is going forward. Historically it's important to understand that both therapeutics platforms evolved from our original core competence which is telomerase biology. In the case of oncology, telomerase is the pan cancer target against which our products are directed. In contrast, the normal expression of telomerase in human embryonic stem cells enables the scalable production of multiple cell therapy products from that starting material. Our strategy in terms of business development on the oncology side is to build a cancer business by developing and commercializing our inhibitor drugs and our vaccine and by licensing oncolytic virus and diagnostic rights to others. On the embryonic stem cell side, the objective is to build a cell therapy company by first demonstrating in man safety and efficacy of the spinal cord injury product and then co-developing with partners other cell therapy products for heart failure, diabetes, musculoskeletal and neurologic diseases. So today Geron is a therapeutic product development company with our first product, the telomerase vaccine, having finished a very successful Phase I/II at Duke; our second cancer product, the telomerase inhibitor drug, scheduled to enter the clinic in the first quarter of next year; and our first product on the embryonic stem cell side, glial cells for spinal cord injury, scheduled to enter the clinic in ‘06. So let's now dive down a little more deeply, first on the oncology program, and then on some of the embryonic stem cell programs.

I said that our oncology platform is based on telomerase, which remains today the only clinically validated, universal and specific cancer target. [Slide 4] All cancer cells depend upon continued expression of telomerase. [Slide 5] Telomerase enables cellular immortality by maintaining the telomeres or ends of chromosomes. Normal cells erode the chromosome end each time they divide until a critical short length is reached and then the cell goes into apoptosis. Tumor cells escape that by this mechanism I'm about to show you. So telomerase, shown here as a ribonuclear protein, binds to the telomere end and in the presence of nucleotide triphosphates they add the canonical T2AG3 repeats to the end of the single strand three prime overhang. At the end of that reaction the enzyme can either translocate and begin that process again continuously on ad infinitum or it can dissociate and find another telomere. So telomerase is the fountain of youth for cells. It operates by maintaining the length of telomeres. [Slide 6] Now the first program I'll talk about is our telomerase inhibitor drug, which as you might expect, because of the ubiquity of telomerase, is literally active against all major human cancers in vitro and it's safe and effective in xenograft models of a growing list of common human cancers. [Slide 7] The drug is based on this molecule here called GRN 163, which is a 13 mer oligonucleotide that is a specific competitive inhibitor of telomerase. This molecule has no antisense activity whatsoever. It does not activate RNA's H. It utilizes a chemistry that our people actually invented, which is critical to the affinity of the drug for the enzyme. So here is the list of tumor types for which this drug is active in vitro – literally all of the major human tumor types of man and the shorter list, but growing, of efficacy and safety in animal models of human cancer. We of course, since we were the first to clone both genes for the protein and RNA component of telomerase, have solid IP protection for the drug itself, the chemistry we use to make it, the target, and of course, the clinical use. Now the way this drug works is very simple. [Slide 8] Here is the mechanism slide I showed a moment ago. The drug fits right in here at the active site. It has a tm of 70 degrees, that means you almost have to boil it to dissociate the drug from the enzyme complex. It shuts the enzyme down and it prevents it from binding the telomere. [Slide 9] Now the clinical formulation of the compound is called 163L because we learned that by lipidating it, putting in a C16 lipid on the five prime end of the molecule, we dramatically alter it's bioavailability and pharmacokinetic characteristics. This is the drug that will enter the clinic early next year. We've received from Dow, our manufacturer, GMP material for the Phase I/II trial and we're about finished now with the in life phase of our IND enabling studies in primates.


Now the reason we are going with 163L over 163 is shown on the following few slides. [Slide 10] First, in vitro cells that express telomerase of various kinds of cancers, and in general the 163L molecule is anywhere from two to 10 fold more potent at inhibiting telomerase in tumor cells than the parent 163. That increased potency in vitro is also expressed in vivo. [Slide 11] Here we're looking at an animal model of human multiple myeloma and we're comparing a high dose of 163, 125 mgs per kilo per week, versus a lower dose of 163L, 75 mgs per kilo per week. And the data are rather striking. It shows first of all that a lower dose of 163L is much more effective at inhibiting telomerase in these cells in the animals. Moreover, that inhibition is translated into a robust loss of telomeric length. So again, less is better than more of the 163L. This is also true from the perspective of the bioavailability. [Slide 12 ] Here's a different model done in Germany of liver cancer. An aggressive tumor that untreated grows to about four sonometers in about four weeks. The point of this slide is to compare again the high dose of 163 in the squares with a much lower dose of 163L in the green triangle and the inhibition of those two curves is indistinguishable. So again a 70 percent reduced dose of 163L in the animal is as effective as a full dose of 163, whether you're measuring reduced tumor growth as shown here, decreased telomerase activity, or decreased tumor cell proliferation. [Slide 13 ] Now the pharmacokinetics of the compound are also markedly different and better. Here we're looking at the degree of telomerase inhibition after a single IV dose of this drug. So again, a high dose 163 is good inhibition initially, but then it wanes over the course of 8 days, compared to the lower dose of 163L which maintains therapeutic inhibition of telomerase after a single injection for over 8 days. [Slide 14] Now we've done a lot of pharmacokinetic modeling. These are the data from rodents, but we've gone through dogs and through monkeys and the difference between 163 and 163L is rather dramatic in terms of tissue half-life. This is a compound that we think will have a half-life in man of about 13 days in certain tissues - a very long half-life. So we've been able now to model through the monkey studies pharmacokinetics for man which clearly show that we can achieve therapeutic tissue levels of this compound with a single IV dose per week. So going forward we have presented this data at the AACR meeting a few weeks ago in San Francisco. We are extending the data in terms of efficacy by demonstrating other tumor types like lung cancer which succumb to this drug in animals as a single agent. We are also publishing combination studies where we're showing synergy between 163L and Taxol in ovarian cancer where we're actually curing animals. We show synergy between 163L and Melfolan in myeloma and melanoma and synergy with Doxirubicin in hepatocellular carcinoma -- in all of those cases, without extending the toxicity of the established compound. Of course the major upcoming news is the filing of our IND which again is scheduled for first quarter of next year.

Second program, already in the clinic, having finished the Phase I/II at Duke, is our telomerase vaccine. [Slide 15] Now our data as you'll see demonstrates that this platform has strong and we think efficacious activity in prostate cancer. Other academic centers using different platforms, but experimenting on telomerase vaccination are showing activity against renal cancer, breast, colon, lung, melanoma and hematologic cancers. So the point here is that telomerase vaccination is beginning to have a long list of tumor types against which it's active, much like the story with the telomerase inhibitor drug, which all turns on the ubiquity of telomerase in cancer. Now our platform is based on autologous dendritic cells - a platform that we in-licensed from Argos Therapeutics earlier this year and the data I'm now going to show you is a combination study in hormone refractory prostate cancer using the platform we licensed from Argos and our telomerase. [Slide 16] So we studied about 20 patients with advanced hormone refractory metastatic prostate cancer. After determining eligibility and obtaining informed consent, patients were leukapheresed once – and one blood collection provides enough cells for from 12 to 20 individual vaccinations. So it is individual, it is ex vivo, but the process is very efficient and provides enough cells for a long course of therapy. The patients were then randomized into one of two arms - either getting RNA of telomerase, plain telomerase RNA, or a LAMP construct that contains sequences that signal the telomerase RNA to be processed by the lysosome system. The objective was to try with LAMP to induce not only CD8 killer T cells, but also CD4 helper cells which you'll see in a moment.


Patients either got 3 weekly doses or 6 weekly doses depending on which dose schedule they were randomized into. [Slide 17] Let's first look at the results for the low dose group, three weekly injections. Well 11 out of 12 patients responded immunologically. We actually think all 12 did and the one who didn't was a lab failure and there were absolutely no adverse reactions. The data look like the following. Here are the 6 patients who received the TERT RNA and on the top line in yellow you see the CD8 response that is specific to telomerase and in the bottom green panel for each patient you see their CD4 counts. And the simple story is in the gray bar here which is before vaccination, the yellow bar here taken two weeks after the third vaccination, you see the enormous uptick in CD8 cells that are specifically responsive to telomerase, and you see that pretty much across the board except for this subject who didn't respond. In contrast, the CD4 levels are very very low in the TERT group. Now when we looked at the LAMP TERT patients, we also saw very good CD8 killer T cell responses, but now we're getting the CD4 helper response that we know to be critical for actually creating memory T cells in these patients which is the objective for the vaccine. So, no adverse reactions, we think virtually everybody responded, and in the LAMP group, both CD8 and CD4 telomerase specific T cells were generated. [Slide 18] Now the story got interesting when we moved to the high dose group, patients who got 6 vaccinations. Again, absolutely no adverse reactions, but now the levels of T cells that we're building up over time - these are the 6 injections here - in two subjects who got telomerase - this is a very different scale - we're now inducing between 1 and 2 percent of the total T cell pool to be telomerase reactive. No one in the oncology vaccine space has ever gotten levels of T cells that high. This is the kind of level that you see in infectious disease vaccination that results in clearance of the infectious particle. Again, when we looked at LAMP in the high dose group, we saw very good, robust CD8 levels and now robust CD4. Again, these are different scales that are in the low dose group. Most significantly, in the manuscript that's about to be published, these CD8s in the LAMP group have a memory phenotype which is what we want to do when we start moving to the boost strategy.


So what have we done that's useful for the disease? [Slide 19] Well, there are two surrogate clinical responses that we think are noteworthy. First, clearance of circulating tumor cells. This is evidence directly that these cells in the blood are active. So there were 10 patients at the beginning of the study who had elevated levels of prostate cancer cells in their blood measured by an RT PCR assay and 9 out of those 10 reduced or completely cleared circulating tumor cells in a kinetic manner that paralleled the induction and wane of the CD8 T cells against telomerase. So here are two subjects that lost a thousand fold of their circulating tumor cells coincident with the induction of CD8 T cells and as those T cells waned, if you remember the kinetics in the prior slide, the tumor cells come back. [Slide 20] So good evidence of correlation of effect. A more traditional measure of efficacy is PSA doubling time, the time it takes for the PSA to double. In the low dose group we saw no significant effect, but in the high dose group, a highly statistically significant prolongation of the PSA doubling time, from 2.9 months pre-vaccination, to over a hundred during the time the T cells were present in the group that got 6 injections. So, next steps here are, we have started a series of small pilot studies at Duke that are exploring slight modifications to the technology we licensed from Merix, now called Argos – they include the use of [onpac] to reduce T regulatory cells, a boosting strategy to maintain higher levels and longer duration of the anti telomerase T cells and we're also looking at a different tumor type that might be a little faster for approval than prostate cancer. You will also hear of the manuscript that we think will be a milestone in cancer vaccination -- it should come out over the next months -- that describes the study in great detail. We are currently now bringing in house the manufacturing process for the vaccine and are beginning to make it into a closed system. Finally, we will select a CMO who will be the manufacturer of the vaccine on contract to us when we move into our own Phase II study.


Just briefly, the two programs in cancer that are outlicensed. The oncolytic virus which is being developed by Cell Genesys under license from Geron. A paper in Cancer Gene Therapy this summer is a good index of what we expect to see here. [Slide21] First, on the left, a model of prostate cancer in a xenogenaic animal. A single IV injection of this virus which contains a telomerase protein promoter was curative of this prostate cancer model. Secondly, in a model of liver cancer, a dose of the virus is shown here, a maximally tolerated dose of doxirubicin is shown here, and the combination is again, curative. Single injection of the virus. And in both of these studies the only place we found live virus was in the tumor cell, testifying to the specificity and power of the promoter. So we do expect Cell Genesys to put one of these constructs into development over the next few months.

[Slide 22] Lastly, telomerase diagnostics. We do commercialize 12 research kits around the world and our partner for clinical diagnostics is Roche who has developed with us a bladder cancer diagnostic that in a 300 patient study in Europe, had a positive predictive value of 84 percent. That means 84 out of 100 people with telomerase in their urine in fact have bladder cancer. This we expect to be marketed under a CE mark in Europe as early as ‘06.

And of course as I mentioned, we have on the telomerase side of the house a controlling intellectual property estate because we were the creators of this field. It covers all of these programs; there are over 200 patents that are issued around the world protecting telomerase.

Let's segue to the other side of the telomerase coin, where telomerase is now the asset that enables embryonic stem cells to divide and live forever. We've surprised everyone, including ourselves, with the amount of progress that we have made. We've learned how to make 8 different therapeutic cell types, differentiated cells, from our embryonic stem cell lines – all of them have normal in vitro function. Six of them are now in preclinical animal testing. Two of our embryonic lines are fully qualified for human use and our first clinical program will be in spinal cord injury and our IND enabling studies for that IND are currently underway. That is scheduled to enter the clinic in ‘06.

[Slide 24] I can't emphasize enough that the expression of telomerase in embryonic stem cells is one of the key factors that separates this platform from all other stem cells. This enables the--expression of telomerase enables us to create scalable manufacturing banks and as you'll see at the end of this part of the talk, manufacturing differentiated cells from embryonic stem cells is much like monoclonal antibody production or biological drug production because of the scaleability of these cells. It's very different from the old world of cell therapy. Let's look at some of these cell types one by one. [Slide 25] The first one is the oligodendrocyte or glial progenitor that we make over a series of weeks from the starting material, undifferentiated embryonic stem cells.

We are working with an animal model of spinal cord injury. [Slide 26] A rat under anaesthesia is given a reproducible blow to the spine and without any treatment is permanently weakened in terms of its lower extremities. I'll show you a movie in a moment to illustrate where the control animals lie. Animals given fibroblasts are really no better than the controls, but animals that are given within a week human glial cells right into the injury have a statistically significant improvement - this is a logarithmic scale - that is stable. Let me show you now a movie of, first, the control animal about 8 weeks after the injury and then a clip of an, one of the animals in the treatment group, about at the same time after the injury. [Slide 27] So, first, here is the animal with no transplant. It's walking by pulling itself on the front paws; the left lower extremity cannot bear weight at all; the right is weak; and the tail is dragged along the bottom of the cage. You see the scar here where the injury was left. And this animal cannot stand on its hind legs. Right. That's the best the control animals get. In contrast, animals who get – sorry, this is the same film – [Slide 28] animals who get the cells support weight on all four extremities and their tail is held off the cage floor and at the very end you can see the animal can support its weight on its two hind legs – right there. That's a pretty dramatic difference, and that's stable.

So the question is why, what have we done? [Slide 29] So when we – sorry – when we sacrifice the animals and look at the lesion site we see two things. First, new neuron growth, which we can quantify to be very dramatic, right at the site of where we've injected these cells. So the glial cells are trophic, they enable new nerve growth at the site of the injury. Second, they create exuberant myelination. [Slide 30] So here are your control animals with very little myelin; here are the animals that received cells – all these little circles are human myelin surrounding the rat axons which could also quantify in both dorsal and ventral lateral column. So these cells are fundamentally re-engineering the injured site, and in a dramatic example of that, [Slide 31] shown here, first the cartoon illustrates that oligodendrocytes can myelinate multiple axons -- in humans 50, 60, 70. Here's an actual picture from one of the animals receiving the cells. Here's the glial cell and here are multiple axons, of the rat, being myelinated by the same cell. So this illustrates generally what this platform is able to do to injury or chronic disease – fundamentally restore tissue architecture and function. [Slide 32] So we're now at the point where we are in IND enabling studies. We have begun our GMP production of the master cell bank from which this product will be made for clinical testing. We're looking at a protocol in which we take patients with lesions anywhere from T2 to L1 first, who require surgical stabilization, at which time the cells will be injected right into the site of the injury. It's an escalating dose study of up to 2 times 10 the 7th cells. There'll be a control group who refuse to get cells. After we do this a few times and establish safety, we're thinking now about moving up into cervical injuries whose patients are on respirators which means a much more objective endpoint than the validated measures we use from motion, locomotor power and sensation. So this is scheduled to begin in ‘06.
The second cell type behind the glial cell is the cardiomyocyte, heart muscle cells. [Slide 33] They make all of the right proteins to show they are in fact bonafide cardiac cells. [Slide 34] They also respond to drugs which illustrates the second general point here, that not only will these cells restore function of the organ, but they will restore pharmacologic responsiveness of that organ because these new cells have drug receptors. So whether it's a calcium channel blocker, an alpha or beta agonist or a phosphodiesterase inhibitor, these cells have the right receptors and respond appropriately to those drugs. [Slide 35] They have normal electrophysiology, they are all ventricular cells and their ventricular depolarization rate–depolarization is proportional to their contractile rate. That's what a normal cardiomyocyte does. When we put them into animals, [Slide 36] you see exuberant engraftment of the human cells in, in this case the rat, which line up and integrate in terms of the sarcomeric myosin. In our first experiments at Stanford in an infarct model where the animal is given a massive infarct, the human cells are injected right into the left ventricle and a month later we come back and do an animal MRI, these are on mice, and what you see is that the cell–the animals that get the cardiomyocytes have actually a fractional shortening [Slide 37] that is normal for the animal compared to BJ fibroblasts or cells, or animals that get no cells whatsoever. So it's a similar kind of story to the spinal cord injury story. We are restoring functional activity in an injured, in this case, myocardium.


Third cell type are islets. And here, in contrast to our other programs, there is no proof of concept required, because the Edmonton Protocol has already demonstrated that cadaveric islets have some utility in treating Type 1 diabetics when those cells are put into the liver. So we have now in fact derived islet cells from embryonic stem cells. They express glucagon and insulin and C reactive peptide and they express insulin in dose response to glucose as a normal islet would. The animal studies are now in progress at Edmonton and I'm pleased to announce that our early results show dramatic prolongation of the diabetic animal's life and human C reactive peptides in the blood of the animals that received these cells.

[Slide 39] What about graft rejection? Well two, two points. First, we are using, we will use low dose immune suppression because the embryonic stem cells are immune privileged. I'll show you that in a moment. Secondly, we have a permanent way to induce immune tolerance to these cells by the use of another cell type called the hematopoetic cell. [Slide 40] This is a mixed lymphocyte reaction. If we mix two different people's blood together, one responds to the other, that's normal. In contrast, if we put undifferentiated, or even differentiated cell types from embryonic stem cells into an MLR, there's no reactivity. In fact, the undifferentiated cell, if added to an active allo MLR inhibits it. These cells contain the same sort of factors that the blastocyst has which prevents the mother from rejecting the implanting 3 day old embryo. These cell types have retained that property.

[Slide 41] The hematopoetic cells we make from embryonic stem cells at low doses actually create stable chimeras in animals. That enables us to do the following. [Slide 42] For any patient, first, they get the hematopoetic cell which makes them immunologically tolerant to any therapeutic cells made from the same embryonic stem cell line. Because all our lines are pluripotent, we can do this with all of our lines. This has been actually worked out in man at Stanford with bone marrow transplantation and renal allografts.

[Slide 43] We are working in the UK on hepatocytes, not for therapy but for drug discovery. These cells have inducible Phase I/II drug metabolizing enzymes and as such are a novel in vitro way to predict hepatic tox and to quantify hepatic metabolism of drugs. [Slide 44] The scaleability of these cells I referred to earlier. We have a culture system now that is completely defined. There is no serum, there is no conditioned medium, all of the additions are recombinant with master files and we have two qualified ES lines. To demonstrate the scaleability, most master cell banks, including ours, have about 200 vials of cells in the bank. At today's efficiency, if we converted all of them to glial cells for our spinal cord injury, we'd have enough cells for 1.3 million doses – that's 5 times the prevalence of spinal cord injury in the United States.

[Slide 45] Our IP is solid behind us. There are 20 issued patents and over 200 in progress, including composition of matter claims for the differentiated cells we make from our lines.

[Slide 46] So that's the Geron story today, a powerful proprietary product pipeline. We have $130,000,000 in cash, a debt free balance sheet. We are the recipient of I think a nice gift from Prop. 71 in California where we are located, which is a $300 million per year for 10 years program to fund California research in embryonic stem cells which we, I think we will benefit from.

So that's the story of Geron. We've moved from a company steeped in science to a company that's now manufacturing three products: the drug, the vaccine and our first cell type from embryonic stem cells.

Thanks very much.





Geron in der Presse !!!

news.google.com/news?q=geron...&tab=wn&ie=UTF-...

Company officials and industry analysts say Geron has few peers worldwide, although competitors are expected to spring up a few years after money from Proposition 71 starts to flow.

" There really isn't much of a stem cell industry," said Joe Panetta, president of BIOCOM, San Diego's biomedical trade group. " It's kind of a stem cell itself."

Human embryonic stem cells have the ability to create healthy new cells and tissues for every part of the body. Supporters say they could help provide cures for such feared ailments as cancer, heart disease and severe burns. The business possibilities are enormous, eventually reaching tens of billions of dollars.

Eighty-two companies worldwide are involved in development of stem cell technologies, according to a 2002 report by the business research firm Kalorama Information.

California firms with at least some stake in stem cells include VistaGen Therapeutics Inc. of Burlingame, StemCells Inc. of Palo Alto, MacroPore Biosurgery Inc. of San Diego and Invitrogen Corp. of Carlsbad.

Kalorama's report said 13 companies were in the best position to capitalize on the emerging technology, but singled out one front-runner: " Geron Corp. is currently the dominant organization in the field," it said.

Geron, first funded in 1992, says only a handful of companies worldwide are doing advanced research on human embryonic stem cells. Other companies mostly are looking at adult stem cells or developing research-related products.

Main Geron competitors have emerged in China, Singapore, Israel and South Korea while the U.S. government discouraged the use of human embryonic stem cells because of ethical concerns: Embryos are destroyed in the process of gathering them.

Industry insiders predict that stem cell business growth over the next five years largely will consist of companies that support Proposition 71 research - for instance, firms that aid the study of stem cells. Once scientists report breakthroughs, look for the formation of more therapeutics outfits.

Exactly how the industry unfolds will be determined partly by the oversight panel governing Proposition 71 money; the panel met for the first time Friday. Among the questions the panel will wrestle with in the coming months include how much of the money will be spent on basic research typically done at universities vs. applied research often handled by companies.

Wayne Johnson, a consultant for the Proposition 71 opposition campaign, said Geron is one of the most likely companies to profit from what he calls " the biggest heist of public funds, probably in the history of the country."

Said Johnson, " This initiative was written very carefully to funnel the money into very specific ... lines of research that are very beneficial to the people who own these patents."

Company President Okarma said before the election that Geron was staying clear of Proposition 71 fund raising. Secretary of state files don't show contributions to the Proposition 71 campaign from Geron, top company officers or its largest stockholders.

Geron's stem cell story started in 1995, when it began funding research into human embryonic stem cells at the University of Wisconsin, Madison, and later at Johns Hopkins University and the University of California, San Francisco.

While federal debates raged about the ethics of stem cell research, Geron kept working - it sponsored the development of the world's first embryonic stem cell colonies - and securing the legal rights to as many of its discoveries as possible.

The company, which also continues to develop anti-cancer drugs, has lost money every year for a total of $255.7 million at the end of 2003 - not an uncommon position in the research-intensive world of biotechnology.

Its investment has generated at least 19 patents worldwide on human embryonic stem cells with 177 pending, the company reported earlier this year. That is believed to be the most extensive intellectual property collection in the industry, covering cells for the liver, heart, bone and nerves.

Today, Okarma says his company is building an intellectual property " fortress" that he hopes will allow Geron to make money whenever and wherever stem cell-based therapies are commercialized.

But Geron's chief financial officer, David Greenwood, said the company isn't trying to stifle competition. To the contrary, he said, Geron aims to stimulate a broad stem cell industry in California.

His approach comes off much softer than Okarma's public statements about the company's " broad, dominating patent estates" and its commitment to " filing of oppositions and interferences against competitors' patents."

Greenwood said Geron is offering its technology free to California university researchers, a common way of getting scientists interested in technologies they otherwise couldn't afford.

But Greenwood also said Geron won't force researchers funded by Proposition 71 money to commercialize new Geron-based products with the company.

Geron still would expect royalties, of course, but Greenwood said researchers could take products to market however they want. " We are quite willing to take this IP (intellectual property) estate and enable others to get into the field," Greenwood said. " I don't spend a lot of time worrying about competitors. I view them as potential partners."

It's the kind of self-help philanthropy the company seems able to afford while its prospects are looking up.

The big break would be if Geron can be the first company to market a stem cell therapy. The company plans human tests of its first stem cell-based product, a treatment for spinal cord injuries, starting in 18 months.

The therapy has proved successful in treating acute spinal cord injuries in rats, which " recover significant motor function" after injection of therapeutic cells, Geron documents say.

At least some Wall Street analysts like Geron's odds. New York investment bank Rodman & Renshaw said in October that it was " pleasantly surprised" that " Geron has made significant strides."

That kind of confidence makes it easier to secure investment for the long road to market. Geron reports having $130 million in cash, but it will have to spend a big chunk of that over the next few years to prove its stem cell therapies work.


GERON CORP.
Headquarters: Menlo Park
President and CEO: Thomas Okarma
Employees: 65
Main business lines: Research-stage cancer and human embryonic stem cell therapies
First funded: 1992
Net loss (2003): $29.9 million
Nasdaq stock ticker: GERN
52-week range: $5.15 to $12.44
Source: Bee research


About the writer:
The Bee's Mike Lee can be reached at (916)321-1102 or mflee@sacbee.com.



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gruss meislo

machen! Ich hoffe Du bist noch drin. Stockst Du jetzt (auch) auf wie ich es erwaege?