Geron mit Hammernews!! (Seite 276)

[mike31]

danke

gruß,
mike31

[meislo]

Teil zwei deiner Frage würde ich Eindeutig den Vorzug geben

gruss meislo

[mike31]

@all,
ist es möglich hier mal eine Antwort auf meine Frage zu bekommen ?

Danke !

[Erbse1]

Herzlichen Glückwunsch
Erbse

[meislo]

Teil 2

Stammzellen

Let`s switch now to the second story, the more medium term or mid-term value driver for the company. And the take home message here in regen med, the embryonic stem cell story, is that we`re positioning for clinical development. You know that this is a new paradigm for therapeutics, doing what pharmaceuticals cannot do – literally re-engineer tissue damaged by chronic disease, that is not an achievable objective for pharmacology. The scaleability of embryonic stem cells allows for the first time a high margin, low cost of goods, product based business model which has never been achieved before in cell therapy.

We`ve demonstrated scalable manufacturing methods for seven different differentiated cell types, the therapeutic cells, that we make from our embyronic stem cell lines and four of those seven are now in proof of concept in animal testing. Two of our stem cell lines have been now, are now fully qualified for use in humans, having passed all of the tests FDA asked us to subject them to to demonstrate their safety for human use. We`ve made dramatic progress in one of the cell types, the oligodendrocyte to treat spinal cord injury which will be our first entry into human clinical trials, and, like the oncology platform we were first in this field; we were funding this research since 1995 and because of that we have a controlling intellectual property estate. So let`s look now at what we`ve actually achieved. You know, the promise of this technology just a few years ago was that embryonic stem cells derived from three day old discarded embryos from IVF clinics would be a self-renewing source for the scalable manufacturing of replacement cells for all tissues in the body. Now that was really a tall order. What have we done to validate that progress–promise?

Well, first, we`ve now made in vitro seven different differentiated cell types and without exception, every one of those cell types has spot-on normal human cell biology. We`ve further learned how to scale and produce them and to purify them for animal testing in major diseases with major unmet medical needs, starting for, from liver cells for drug development all the way through diabetes, Parkinson`s Disease, heart failure and so on. And I`m, now, take you through a few of these cell types to give you a feel as to where we are.

First are liver cells. Now you know that drug discovery is hampered by not having an, a source of liver cells to not only test for liver toxicity but more importantly to completely to find hepatic metabolism of drugs before patients are entered into Phase I trials. We have developed such a platform. The stem cell derived hepatocytes make all of the superficial markers that human hepatocytes from biopsy make as well as expressing the full complement of Phase I and Phase II drug metabolizing enzymes. So we`re now seeking a partner, perhaps in the UK, that will help us format these cells for medium to high throughput screening and beta test them in the pharmaceutical sector in the coming months.

We`ve derived hematopoetic cells, blood forming cells. These are in animal studies in Canada where we`re demonstrating engraftment and the production of all three blood lines. The reason for deriving these cells is our approach to avoid immune rejection of the therapeutic cell. We know from bone marrow transplant studies that if I receive a low dose of these hematopoetic cells made from stem cell line A, I will become permanently tolerant, immunologically, to any therapeutic cell made from that same stem cell line. So this is how we plan to avoid the exposure of costly and toxic immune suppressive agents to the patients who`ll be taking the therapeutic cells. In our Geron Biomed subsidiary in the UK, we`ve published this summer on making bone forming cells, osteoblasts. The bone that these cells make is spot-on normal bone of humans as assayed by x-ray defraction. These will be put in animal studies of nonunion fractions-- fractures in the coming months.

We`ve talked for some time about insulin producing islet cells to treat diabetes and I can tell you now that although the efficiency is still low, we have produced insulin secreting and glucagon secreting cells - the cells of the islets in sufficient quantity to move into animal studies and I can also tell you now that these islet cells are glucose responsive. They secret insulin in proportion to the amount of glucose in the media, which is, of course, the gold standard for real human functioning islets. Now in contrast to many of the other diseases, diabetes is one in which we already have human proof of concept, the Edmonton Protocol, in which cataveric islets are injected into the livers of diabetic patients. This will take the place of that approach.

Dopaminergic neurons for Parkinson`s Disease. We have published now on the fact that these cells are completely normal. Dopaminergic neurons, they make dopamine. They have tyrosine hydroxylase. They respond to dopamine, they make synapses. They do all the right things that dopaminergic neurons are supposed to do. We`re at, in now animal proof of concept studies at Geron where we are transplanting these cells to the deep nuclei that are the source of the problem in Parkinson`s Disease and we are getting exuberant outgrowth of human dopaminergic neurons which we hope to demonstrate in more chronic studies will actually re-engineer including to the cortex the entire dopaminergic circuit which is abnormal in Parkinson`s Disease

Cardiomyocytes. Heart muscle cells which spontaneously contract and have, again, completely normal cell biology, including dose response curves to heart drugs clinically used today. These cell types are also in animal studies where we`re showing engraftment of these human cells, and, more importantly, integration of them with the animal`s normal myocardium, electrically and mechanically. The next milestone will be the announcement of the results of these cells transplanted into mouse models of heart failure where we hope to demonstrate improvement in cardiac output, again through specific transplantation of cell types.

Our most advanced cell type is the oligodendrocyte, the cell that makes myelin, or the insulation that surrounds neurons. The objective of the exercise here is to apply these cells to spinal cord injury which we`ve now done in a validated model of human acute spinal cord injury. These animals under anesthesia are given a uniform blow to the spine which results - in red - into a permanent paresis of the animal. And I`ll show you a movie in a moment to demonstrate the best that the control animals get. In contrast - in blue - animals who get the human cells have a statistically significant improvement in their function, which I`ll also illustrate now with a movie that tells this story in a few words.

First, here are the animals that get no treatment. The left lower limb is completely paralyzed, the animal cannot lift its tail off the bottom of the cage. This is permanent. This is the best the animals get. This is at nine weeks after injury. In contrast, animals who receive the oligodendrocytes lift their tail completely off the cage, bear full weight on both lower extremities and although you can`t see this at the very end , they`re actually able to stand on their hind paws, a dramatic result. When we sacrifice the animal and ask why is this happening, we see that the lesion site is actually containing regenerating rat neurons - a very important endpoint - due to the injection of the human cells, and, at the same injury site we now see human myelin surrounding the previously unmyelinated injured animal neurons. We also have data now in a second animal model, the [shiverer] mouse which is genetically unable to make mouse myelin, and we see the same myelination pattern which obviously must come from human cells.

We now have, as I mentioned, two lines, different lines, both derived at Wisconsin, that are qualified for human use, having passed the full battery of tests that rule out human, porcine, bovine or murine viruses. We are making new lines as we speak that have never seen any animal material and as such will be [GNP] in their characteristics. The, in terms of the scaleability, let me give you one example. If we took one master cell bank of embryonic stem cells and devoted all of them at current efficiencies to the production of the glial progenitor cells that we use for spinal cord injury, one master cell bank would produce enough doses of oligodendrocytes to serve as the entire prevalence of spinal cord injury in the United States. So the take home message of this manufacturing capability is that these cells are really the monoclonal antibodies of cell therapy because of the scaleability and low cost production that`s never been possible with cells before. That enables us to segue from the traditional, individualized cell therapy production schema where there are more people per patient making the dose to an automated, closed system that gives us batch production, multi doses of cells per run.

Our patent portfolio is enormous. The numbers of course speak to themselves, but more importantly is the characteristic of the claims - they`re broad, they`re unrestricted, they`re well exemplified by the body of the patent and not only give us a dominant position today, but will give us freedom to operate and will withstand subsequent challenges as these programs move into the clinical and commercial realms




die Zsammenfassung


So, in closing, the take home message for oncology, the taproot of Geron based on telomerase is that we`ve clinically validated this target. The vaccine trial at Duke shows safety and efficacy against metastasizing cancer. The oncolytic virus has been demonstrated by our partners to be safe, efficacious, and synergistic with chemotherapy. The inhibitor drugs are a novel class of nontoxic drugs that have potential for broad clinical application because every cancer type obligatorily depends upon telomerase to progress, and these drugs shut it down.

On the regen med side, we are positioning for clinical development. We`re doing the things now that will enable us to move these products, cell type by cell type, through the regulatory pathways which, by the way, are well defined. This is not a black box of how we get cells approved. The rules have been codified in over 15 years of prior cell therapy attempts. This is going to fall right into the realm of biological drugs. So we can make seven different cell types for therapy. They all have normal cell biology, we can make them scalably and we have animal proof of concept for four of them. We have two lines fully qualified for human use. We think the spinal cord application will be first to the clinic which will be a dramatic human proof of concept for us, much like the vaccine is for the cancer vaccine. We have multi dose production lots that for the first time enable a high margin, low cost of goods, product based business model for cell therapy where the output of the production is vials of cells shipped frozen for off the shelf use in medical centers. And, of course, the intellectual property estates are controlling for both programs. We have a balance, cash, a balance sheet and a cash burn that enables us to create a sustainable environment for product development. We`ve done the hard but the right thing in reducing our burn twice, once last year in June and once this year in January, as we shift from discovery to product development. So going forward you will hear more about the vaccine trial as we finish enrolling the Phase I/II patients and can share with you the clinical results in addition to the safety and immunologic responses you`ve heard today. You`ll hear more publications and more talks about 163 and 163L as we move forward in our IND enabling studies with those compounds and hopefully you`ll hear more about Cell Genesys`s plan to develop the oncolytic virus clinically in cancer.

On the regen med side, you`ll hear more publications on animal proof of concept. We hope soon to talk about the impact of cardiomyocytes on cardiac output in animal models of heart failure. The publications for the spinal cord injury model will appear in peer reviewed journals. We hope to be able to describe new cell lines derived in the United States that are [GNP] and that are complete–are made under completely defined conditions. Again, all elements toward the goal of positioning for clinical development.

Thank you for listening to our story.



Viele Grüsse und viel Spass beim lesen

meislo

[mike31]

@all,

wird es morgen zu massiven Gewinnmitnahmen kommen oder sind wir erst am Beginn einer goßen Story ?

Gruß,
mike31

[meislo]

Praentation von gestern zum lesen

Teil 1

Oncology (Krebsbehandlung)


Okay. Good afternoon. Like to introduce our next speaker, Dr. Thomas Okarma, President and CEO of Geron.

Dr. Okarma: Thank you, David, and thank you all for coming today. I know this won`t surprise you but I too will be making forward looking statements so we call your attention to the risk factors in our 10Q.

We have two stories to summarize for you today and I`m going to start with oncology, the cancer platform, which is really our near term value driver. And the take home message for you today in cancer is that we believe we`ve now clinically validated the telomerase target. You may know that telomerase remains today the only known universal cancer target, meaning, it`s expressed in all cancer cells and very rarely in normal cells. We have three therapeutic programs that address different elements of telomerase in cancer.

The most advanced is our Phase I/II trial in prostate cancer at Duke where we`re now showing and I`ll give you the data today, that telomerase vaccine, vaccination safely induces strong anti cancer immune responses in advanced cancer patients.

We have an oncolytic virus program as well, initially licensed to GTI/Novartis, now acquired by Cell Genesys where we have now shown in multiple animal studies dramatic efficacy and synergy with chemotherapy.

And lastly, our home run, the telomerase inhibitor drugs, 163 and the newer variant 163L. Literally, these compounds are effective in vitro against all the major human cancers and in animal models have been effective in all six models that we have thus far exposed these drugs to. So let`s go a little bit deeper into this, and of course recall that telomerase is the tap root of Geron and as such we have a controlling intellectual property estate on the platform and the products you`re about to hear.


The trial at Duke we`ve described in April. It is a two phase trial with a low dose group of 12 patients and a high dose group of 12. We reported some of the preliminary results back in April which I`ll now remind you of. First, all of the patients in the low dose group - all 12 of them - responded with vigorous immune responses specific to telomerase. All of these red bars are T cells that react specifically to telomerase in all of the patients, and this is significant because these are advanced cancer patients who are by definition immune suppressed. We also demonstrated in the first low dose group that all 7 of the patients who had elevated circulating levels of metastasizing prostate cancer cells had those levels reduced to zero concomitant with the vaccination. Some of these patients lost over a thousand fold of circulating prostate cancer tumor cells – no patient did not respond to this vaccine in that way.

The new data that I can share with you today is the beginning of the results from the second phase, the so-called high dose group who received six vaccines instead of three in the low dose group. And there are several points of importance to be made here. First the absolute level of T cells that we are generating in these subjects in the high dose group is between one and two percent of their total T cell pool; that`s never been achieved in cancer vaccination. That`s the level of T cell reactivity you see with measles or mumps vaccinations. Second, the duration of the immune response appears to be very long lived, well after the sixth vaccination and in fact the stabilizing level of T cell immunity in the high dose patients - at 13 weeks - is higher than the peak level we got in the low dose group where we demonstrated the efficacy with regard to circulating tumor cells. So we`re very excited that by simply adding three more injections of the same number of cells we`ve gone from a short term low but effective immune response to one that appears to be long lived. So stay tuned later in the year when we now, when we unveil the results of the rest of the high dose group and focus on clinical responses.

We have good surrogates now for immune response which is the skin rash these patients develop at the injection site. We have actually biopsied this delayed hypersensitivity reaction and shown it to contain anti telomerase T cells. So we now have a visual measure of the immune response.

And none of the patients in the low dose group or the high dose group have experienced a single adverse reaction.


Another piece of evidence on the vaccine side came to us indirectly. In another trial not sponsored by Geron at Duke in renal cell carcinoma when the patients were immunized with total tumor RNA we knew that they had responses, responses to laminen and specific antigens in renal cell carcinoma that had been known, what we didn`t know until we did the analysis though was that the dominant antigen in the total tumor RNA in these patients is in fact telomerase - and these patients are enjoying clinical responses.

So those two lines of evidence show that when you target telomerase you get effective anti tumor immunity and no side effects.

Let`s turn quickly to the oncolytic virus. This is a genetically engineered virus in which we control the replication of the virus with the telomerase promoter, the on/off switch. So the only way the virus can replicate and kill the cell it`s replicating in is if it`s in a telomerase positive tumor cell. And we and GTI/Novartis have published on the specificity of this virus before. So what I want to show you here is work also done at GTI that shows synergy of this virus with doxyrubicin. So here we`re measuring tumor volume, the spread or growth of the tumor, of a liver cancer in an animal. The virus alone is shown here in blue with a effect that is significant over control. Here is doxyrubicin by itself. At this dose slightly more potent than the virus by itself. But in these two lines we see the combination of that dose of virus and that dose of doxyrubicin, which is literally complete control of the tumor. Very dramatic synergy. And, again, because we control the replication of the virus elegantly to telomerase, there`s no adverse events in these animals. So we look forward to the continued development of this technology with Cell Genesys



Teil 1/b GRN163/163L wobei 163L die neue Bezeichnung für 719 ist also nicht wundern wo GRN 719 geblieben ist



Now the final entry in the oncology space we think are our home run compounds, GRN 163 and its lipidated cousin GRN 163L. Now it`s now agreed upon worldwide by basic scientists and oncologists itself, themselves, that, that cancer progression is inexorably linked to telomerase activity. It is still the only universally validated cancer target. We have worked for a long time to try to generate drugs that are as specific against telomerase as telomerase is specific to cancer to leverage that value of that target. And we have done that with these two compounds which are potent, specific, and absolutely nontoxic inhibitors of telomerase. We have literally demonstrated that 163 is active in vitro against all of the major human cancers in man shown here. We`ve begun now to do animal studies with some of these tumors, and these six cancers are effectively suppressed in vivo in animal models with GRN 163: brain cancer, prostate cancer, lymphoma, myeloma, liver cancer and cervical cancer, and I`ll show you a bit of that data today to give you a feel for how dramatic this compound may be clinically.

This is a picture of 163. A space occupying molecular model. It`s a 13 mer oligonucleotide, 13 building blocks. It is not an antisense molecule. It has no antisense activity whatsoever. It is a direct competitive inhibitor at the active site of telomerase and it is the only molecule in the human body to which this compound binds. It is effective both intratumorally, and I`ll show you that data in a moment, as well as parenterally. We are doing multiple GLP toxicology studies now, we have multiple manufacturing contracts in place and have IP protection not only for the compound but for the unique chemistry that makes it so potent and specific, as well as the target and issued IP for the clinical use of this compound to treat human patients with cancer. Now we`ve shown these data before, the intratumoral application of 163 in animals bearing a very malignant form of brain cancer and the results are quite striking. All the control animals are dead by day 43, 5 of 7 of the treated animals are alive and well at the time they are sacrificed by protocol at which time they are examined histologically for any evidence of residual tumor, and 5 of the 7 animals show zero tumor in their brain. Now that wouldn`t be so surprising if 163 were a toxic compound, but those same animals show absolutely no adverse reactions whatsoever. This is truly a new paradigm in chemotherapy for cancer: specificity, efficacy and the absence of toxicity.


Some new data that I`ll share with you today from Sloan Kettering here in New York in Malcolm Moore`s lab. This is disseminated multiple myeloma done in a way that the colors indicate the spread of the tumor in the animal - so blue color going to red is the presence of the multiple myeloma in the animal`s body. So here on the control animal, as you can see, dramatic spread of the cancer throughout the animal. Here is the maximally toxic--tolerated dose of doxyrubicin, the best compound to be used in this form of cancer and it`s actually somewhat worse than PBS control. In contrast, seven days of treatment with 163 systemically produces this dramatic result, colorometrically that you can see visually , the absence of blue which when quantified shows dramatic efficacy 30 days after the onset of, after the introduction of the cancer. So another example of the systemic potency of 163 as a stand-alone agent in a remarkably malignant tumor which outperforms doxyrubicin at its maximally tolerated dose, and, of course, we enjoy a substantial survival benefit which obviously is the exercise at the end of the game. Now 163L which we used to call 719 is the lipidated version of 163. It`s the same molecule, same chemistry, but we hang covalently a lipid molecule on one end of the drug. This has enormous impact and we are now doing head-to-head studies of 163 vs. 163L in tox, in efficacy, in synergy, in PK, so that we choose the best compound to move forward into the clinic. Clearly the drug has enhanced bioavailability, which I`ll show you, and potency. It also has manufacturing advantages. It`s less expensive to make and, of course, was designed for systemic administration. So here`s the kind of data we`re getting when we compare 163 head-to-head with 163L. Blue is PBS control, the pink is 163 and the green is 163L at a lower dose than 163 done in the same model. So what you see is a low dose of 163L is much more effective than a higher dose of 163 in inhibiting telomerase in the cells in the animal, in the, in the cancer. Also, the length of telomeres, telomere shortening, which is the mechanism of action, at the lower dose of 163 is more potent than the higher dose of – I`m sorry – the lower dose of 163L is more effective at shortening telomeres than the higher dose of 163. If we now look at the whole animal data, we see the same story. The lower dose of 163L is more potent in terms of tumor inhibition in the animal than the higher dose of 163. So those are the kind of data that we`re now getting that augur well for the clinical introduction of the lipidated form of this bio-molecule.


We are now in the toxicity phase of testing 163L and we have finished a 14 day ascending toxicity dose in mice where animals have been given up to three times the therapeutic dose you saw before with absolutely no apparent toxicity at any dose in any organ. So we think in the oncology platform now we`ve achieved three product formulations that have a very exciting future: the vaccine which is demonstrating safety and activity in prostate cancer in a Phase I/II today; the oncolytic virus which will be developed by Cell Genesys up the street from Geron; and our home run, the telomerase inhibitor drugs which should enjoy broad use in combination therapy for virtually all forms of cancer.

Let`s switch now to the second story, the more medium term or mid-term value driver for the company.

[meislo]

Geron in aller Munde zur Zeit in cnbc

gruss meislo

[meislo]

UPDATE - Geron shares soar on CEO cancer vaccine comments
Tuesday September 23, 2:13 pm ET


(Updates stock price, adds details)
NEW YORK, Sept 23 (Reuters) - Shares of Geron Corp. (NasdaqNM:GERN - News) rose about 40 percent on Tuesday to their highest level in nearly two years after the biotechnology company`s chief executive reported optimistic results from early-stage testing of its experimental anti-cancer therapies.

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Chief Executive Thomas Okarma, speaking at a life sciences conference after the close of trading on Monday, said Geron believes it has "clinically validated" its approach to fighting cancer by generating an immune response to an enzyme in cancer cells called telomerase.

The Menlo Park, California-based company currently has three oncology programs in development, with the most advanced in an early stage trial of a prostate cancer vaccine.

Okarma said the vaccine safely induced strong anti-cancer immune responses in all patients in the very small-scale trial without a single adverse reaction.

Geron in April released results of its low-dose testing of 12 advanced cancer patients. Okarma on Monday discussed initial results of its 12-patient high-dose study.

"We are very excited that by simply adding three more injections of the same number of cells, we`ve gone from a short-term, low, but effective, immune response to one that appears to be long lived," Okarma told the meeting.

Complete results from the high-dose phase of the trial are expected to be released by Geron later this year.

"This was the first peek at the high-dose group but tends to suggest that the results they will report in December will be favorable, and potentially better than the low-dose group," Ren Benjamin, an analyst for Rodman & Renshaw, told Reuters.

"They seemed to be able to generate a significant immune response," he added.

Geron shares were up $3.77, or 39.5 percent, at $13.34 in afternoon trade on Nasdaq after reaching a session high of $13.49. The stock was trading for just $1.41 in March before Geron released its preliminarly low-dose trial results.

[meislo]

Im augenblick bei 13,25 Dollar

Geron Shares Rise on Positive Cancer Study Findings
Tuesday September 23, 12:22 pm ET
By Daniel Rosenberg


CHICAGO -- Shares of biotech company Geron Corp. (NasdaqNM:GERN - News) soared Tuesday after its chief executive announced positive early findings from a prostate cancer vaccine study late Monday.
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Dr. Thomas Okarma, Geron`s CEO, said Monday at the UBS Global Life Sciences Conference that Geron`s Phase I-II trial of a prostate cancer vaccine targeting telomerase, a protein highly expressed and specific for cancer cells, has met a key goal.

"We`re now showing that telomerase vaccination safely induces strong anticancer immune responses in advanced cancer patients," Dr. Okarma said at the conference.

Analyst Ren Benjamin of Rodman & Renshaw said this is good news for Geron.

"In previous results, they showed they were able to reduce levels of circulating prostate cancer cells almost to zero" with a group of patients receiving a low dosage of the vaccine, Mr. Benjamin said. The new results, which he believes come from patients receiving a higher dosage, appear to be similar, if not better.

He said the trial`s final results are expected by the end of the year.

"It`s definitely progress and it looks really good," Mr. Benjamin said. "It has potential not only in prostate cancer but as a universal cancer vaccine."

Telomerase, Dr. Okarma said at the conference, remains the only known universal cancer target. It is expressed in all cancer cells, but very rarely in normal cells.

"The take-home message for you today in cancer is, we believe we`ve now clinically validated the telomerase target," Dr. Okarma said.

Around noon on the Nasdaq Stock Market (News - Websites), shares of Geron were up $1.63, or 17%, at $11.20.

In his speech at the UBS conference, Dr. Okarma said Geron is beginning to look at the 12 patients in the high-dosage section of its prostate cancer vaccine trial, and so far there`s a lot to like.

The high-dose patients received six vaccine injections rather than the three received by the 12 low-dose patients. These high-dose patients have generated a high level of T-cells, which are a type of white blood cell. T-cells help fight cancer as well as infectious disease.

"The absolute level of T-cells we are generating in these subjects in the high-dose group is between 1% and 2% of their total T-cell pool," Dr. Okarma said. "That`s never been achieved in cancer vaccination. That`s the level of T- cell reactivity you see with measles or mumps vaccinations."

He added, "The duration of the immune response appears to be very long lived, well after the six vaccinations. We are very excited that, by simply adding three more injections of the same number of cells, we`ve gone from a short-term low but effective immune response to one that appears to be long lived. So stay tuned later in the year when we unveil the results of the rest of the high-dose group and focus on clinical responses."

In April, the company released preliminary results from the 12 low-dose patients. The data showed the vaccine able to reduce levels of circulating prostate cancer cells almost to zero. There were no adverse effects, nor have there been to date with the high-dose group.

"You`re seeing a more robust immune response" in the high-dose group, Mr. Benjamin said.

There are one million patients with prostate cancer in the U.S. and 189,000 more cases diagnosed yearly. Mr. Benjamin believes the telomerase vaccine, if commercialized, has a market potential greater than $1 billion.

Mr. Benjamin rates Geron a market outperform and doesn`t own shares. There is an investment banking relationship.

-By Daniel Rosenberg, Dow Jones Newswires; 312-750-4118 [e-mail]




gruss meislo