Drugs To Watch: Early Stage - 500 Beiträge pro Seite

[Neoe]

Als Gegenstück zum anderen "Drugs To Watch"-Thread, fände ich auch die Diskussion über sehr vielversprechende, vielleicht bislang unbeachtete Medikamente in der frühen Phase interessant (Phase I und Phase II). Neben Infos zur Therapie, wäre auch hier eine kurze Vorstellung des Unternehmens interessant.

Ich bin wirklich gespannt, wie die "Drugs To Watch"-Threads sich entwickeln. Wenn man sich hier wirklich die Mühe macht alles up-to-date zu halten, könnte sich das für uns alle auszahlen.

[BrauchGeld]

Hi Neoe

Ich finde deine Idee nicht schlecht hoffentlich machen viele mit .
So wie es aussieht mache ich wohl den anfang.

Also ich hab ein paar Biotechfirmen die ich für sehr aussichtsreich halte .

Ich fange heute mal mit der Australischen Biotechfirma Progen(pgl.ax) (Nasd:Pglaf)an.
Das Produkt PI-88 in Phase 2 hat blockbuster Potenzial.Bisher waren die Forschungsergebnisse gut.

Kurs: 2,97$ oder 4,30 a$ Mk:knapp 90 mio $

Business summary:
Progen Industries Limited is an Australian-based, globally focused biopharmaceutical company engaged in the discovery, development and commercialization of small-molecule therapeutics for the treatment of cancer and other serious diseases. The Company`s lead product candidate, PI-88, is one of a new class of multi-functional, multi-targeted cancer therapeutics inhibiting both angiogenesis or tumor promoting factors such as Vascular Endothelial Growth Factor, Fibroblast Growth Factor 1 and basic Fibroblast Growth Factor, as well as heparanase, an enzyme implicated in metastasis (tumor spread). As of the fiscal year ended June 30, 2003 (fiscal 2003), PI-88 is being studied in two clinical trials at the United States under an active investigational new drug (IND) application with the United States Food and Drug Administration (FDA).

Hier was übers Produkt PI-88:

--------------------------------------------------------------------------------
PI-88 is Progen`s most advanced compound within its oncology pipeline. Historically, PI-88 was the result of a fully funded research collaboration with Professor Chris Parish`s group at the John Curtin School of Medical Research at The Australian National University (ANU). PI-88 is a new antiangiogenic therapeutic currently in multiple international Phase II clinical trials under an Investigational New Drug (IND) Application with the U.S. Food and Drug Administration (FDA). PI-88 has shown a good safety and tolerability profile in numerous preclinical and clinical studies and promising signs of efficacy in humans are emerging from the clinical program. The current Phase II clinical program includes investigation of PI-88 for lung cancer, (NSCLC), primary liver cancer (hepatocellular carcinoma), multiple myeloma and melanoma (for which PI-88 has received Orphan Drug status from the US FDA). PI-88`s novel mode of action indicates that it may show patient benefit across many cancer types.
The PI-88 Advantage
Trials of multiple therapies have recently validated angiogenesis as a target in oncology.
The effective inhibition of angiogenesis is likely to require a multi-targeted approach.
However, inhibiting angiogenesis might promote metastasis, therefore new anti-angiogenic therapies might need to concurrently control metastasis.
A multi-target and novel antiangiogenic/antimetastatic approach, combined with a good safety and tolerability profile, is a key differentiator between PI-88 and other antiangiogenic investigational drugs based on the evidence to date. It may well provide a competitive advantage over targeted agents that rely only a single mode of action.

PI-88`s Mechanism of Action
The major issues for the treatment of cancer remain: the need to attack the growth of the primary (original) tumour, to inhibit the establishment and spread of secondary tumours (metastasis). PI-88 has been demonstrated to address both of these issues simultaneously, by utilizing the mechanism of heparan sulfate mimicry.
PI-88 retards the growth of primary tumours by inhibiting new blood vessel growth (angiogenesis) in three ways:

Heparan sulfate mimicry causes inhibition of heparanase, which prevents the release of angiogenic growth factors from the extracellular matrix (ECM).
Interaction with angiogenic growth factors VEGF (Vascular Endothelial Growth Factor), FGF-1 (Fibroblast Growth Factor -1) and FGF-2, reduces their functional activity. PI-88 binds with high (nanomolar) affinity to these growth factors.
Stimulation of the release of Tissue Factor Pathway Inhibitor (TFPI), an endogenous protein that has anti-angiogenic and anti-coagulation properties.
Inhibition of heparanase and stimulation of TFPI release are also jointly responsible for the antimetastatic activity of PI-88.

Hier der Pipeline Link:
http://www.progen.com.au/?page=pihome.html


Viele Grüsse
B.M.

[Neoe]

Hallo BrauchGeld, schön dich gleich hier zu sehen. Zum Thema Australien fällt mir spontan auch noch Australian Cancer Technology ein:

Pentrix befindet sich in Phase II und könnte mal ein Blockbuster werden:


Australian Cancer Technology Ltd

Overview

Australian Cancer Technology (“AustCancer” ASX:ACU) is a broadly based international oncology company developing a portfolio of high quality oncology-related projects that are at various stages of commercialisation. Cash generating businesses will provide the funds to exploit the potential of its leading products and to introduce promising pre-clinical and Phase I projects into the development pipeline. Its leading edge Pentrix™ anti-cancer vaccine successfully completed Phase I and Phase Ib/IIa trials at St. Vincent’s Hospital Sydney and will soon undergo a comprehensive Phase II trial with prostate cancer patients in Melbourne. AustCancer’s US subsidiary, revisys™, is launching a range of nutritional supplements designed by leading US scientists for people with special needs, including those undergoing cancer treatment. That business is expected to be cash positive in year one. The company is also broadening its cancer therapeutic development pipeline, which currently includes a new oncology drug (CHK1 Kinase Inhibitor) to optimise the efficacy of chemotherapy and radiotherapy. AustCancer plans to list on NASDAQ in the near future.

Competitive Advantages

AustCancer -

A management team and board with extensive experience in the management of public companies, biotechnology companies and in scientific research both in Australia and internationally.
Worldwide exclusive licence to commercialise the Pentrix™ vaccine (described below).
Strategic alliance with BioFocus plc, a leading UK based drug discovery and chemistry service provider listed on AIM, which gives AustCancer ongoing access to a product pipeline of potential treatments.
A flexible listed structure with the capacity to accommodate a number of commercial structures to suit potential partners.
A USA based complementary medicine business (revisys) which will generate cash and valuable US contacts
Pentrix™ Vaccine -

Has the potential to treat up to 50% of all cancers unlike most cancer therapies which are targeted at very specific cancer types.
Does not involve the use of cells as is common with current cancer vaccines. This gives Pentrix™ advantages over competing technologies due to reduced cost of production, reduced time taken for treatment and less complex regulatory issues.
Many cancer vaccines have to be individually tailored to the patient. The Pentrix™ vaccine is universal, the same vaccine being administered to all patients.
Technology


PentrixTM cancer vaccine-

Broad-spectrum cancer vaccine which targets mutations in the p53 tumour suppressor gene.
Mutations in the p53 gene are present in up to 50% of all cancers.
The PentrixTM cancer vaccine is an anti-idiotypic vaccine, which overcomes the issue of self-tolerance, which is a major barrier for most cancer vaccines.
Patent, which covers a panel of synthetic human antibodies produced by the p53 tumour suppressor gene. These are the only human p53 antibodies currently available in the world.

[greenhorn1998]

Hallo zusammen!

Echt eine richtig gute Idee, Neoe. Respekt! Nun ja, ich wollte hier an dieser Stelle einmal Geron vorstellen, wohlwissend, dass die Meinungen über das Unternehmen hinsichtlich seiner (äußerst) vielversprechenden Stammzellen-Technologie und den damit verbundenen ethisch-moralischen Diskussionen weit auseinander gehen werden. Auch ich bin mir der Problematik bewusst. Hinzu kommt, dass Geron wirklich noch weit entfernt davon ist, Geld zu verdienen - auf dem Weg dorthin kann noch einiges passieren. Allerdings ist das ja der Thread in dem "Early-Stage-Wirkstoffe" vorgestellt werden können.

Nun, es soll in diesem Zusammenhang auch gar nicht um Stammzellen gehen, denn auch hinsichtlich der Bekämpfung von Krebs ist Geron extrem (!) interessant. Wie ich finde.

Zwei sich in der Pipeline befindende Produke möchte ich an dieser Stelle vorstellen.

Cancer Programs : Telomerase Cancer Vaccine (TVAX)
The goal of therapeutic cancer vaccines is to “teach” the patient’s own immune system to attack cancer cells while sparing other cells. This is done by exposing the immune system to a substance (an antigen) that is as specific to cancer cells as possible, thus inducing an immune response to any cells that present that antigen. We believe that telomerase’s characteristics make it an ideal antigen for cancer vaccines.

We are conducting basic and clinical research to confirm the safety and efficacy of telomerase vaccine therapies. In collaboration with scientists at Duke University, we published studies in the September 2000 issue of Nature Medicine, which demonstrate that cancer patients’ immune cells can be activated with a telomerase vaccine in the laboratory to kill their own cancer cells. This technique was also effective in reducing tumors in animals. A Phase I/II study in prostate cancer patients at Duke University Medical Center is currently underway using this approach.

The Duke Phase I/II clinical trial uses an ex vivo (outside the body) process. Dendritic cells (the most efficient antigen-presenting cells) are isolated from the patient’s blood, pulsed with telomerase RNA, and then returned to the patient’s body where they instruct cytotoxic T-cells to kill tumor cells that express telomerase. This clinical trial is designed to enroll up to a total of 24 patients with metastatic prostate cancer, 12 of whom receive three weekly vaccinations (low-dose group), and 12 of whom receive six weekly vaccinations (high-dose group). As of June 1, 2004, the Duke researchers had treated and analyzed results for twenty patients.

None of the patients have shown treatment-related adverse effects to date. All of the patients in the low-dose group showed a significant cellular immune response specific to telomerase. Levels of circulating cancer cells were reduced to normal in six of the eight patients who had significantly elevated levels of cancer cells circulating in their blood before the trial; and for a period of three months after treatment, PSA levels stabilized or declined in all three of the patients who had rising levels of PSA when they entered the study.

Seven of the eight patients in the high-dose group responded to the vaccine by generating telomerase specific cytotoxic T-cells. Patients in the high-dose group responded with a dramatic telomerase-specific T-cell response that increased over the treatment course and peaked 2 to 4 weeks after the final dose. Peak levels of their telomerase-specific T-cells were remarkably high, ranging from 0.9% to 1.8% of the total circulating cytotoxic T-cell pool. Telomerase-specific T-cells were detected for at least 16 weeks after vaccination.

Although the trial is 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 in the trial who were found to have elevated levels of circulating prostate cancer cells at the onset of the study, nine exhibited substantial reduction or complete clearance of their circulating tumor cells during the period in which telomerase specific T-cells were detected in the blood.

We own the rights to the telomerase antigen and its use in therapeutic vaccines. We also have a co-exclusive license from Merix Bioscience, which holds the rights for the ex vivo dendritic cell processing technology used in the Duke clinical trial. Under that license, we can use the technology with any defined antigen, including telomerase, to treat cancer.

In addition to our own development, we have granted a non-exclusive license to Dendreon Corporation to develop an ex vivo telomerase vaccine using Dendreon’s antigen-presenting system. In addition, we are pursuing the development of in vivo telomerase cancer vaccines. Geron scientists have demonstrated that direct, in vivo vaccination in tumor-bearing mice elicits a telomerase-specific immune response and causes reduced growth of the animals’ tumors. Direct vaccination would eliminate the need for manipulation of dendritic cells in culture and potentially allow straightforward vaccination procedures to be available for all cancer patients in any oncology clinic.






GERON REPORTS PRESENTATION OF FURTHER RESULTS OF TELOMERASE CANCER VACCINE CLINICAL TRIAL AT DUKE UNIVERSITY MEDICAL CENTER
Menlo Park, CA – December 8, 2003 – Geron Corporation (Nasdaq: GERN) today announced the presentation of additional positive preliminary results from a Phase I/II clinical trial of a telomerase therapeutic vaccine for metastatic prostate cancer at Duke University Medical Center. The results were presented today at the American Society of Hematology (ASH) annual meeting in San Diego, California, by the principal investigator on the clinical trial, Johannes Vieweg, M.D., Associate Professor of Urology and Associate Professor of Immunology at Duke.

Dr. Vieweg’s presentation reported that all but one of the patients in the clinical trial evaluated so far showed strong telomerase-specific cellular immune responses, that no patients exhibited any sign of treatment-related adverse effects, and in three of three patients thus far analyzed from the high-dose group, stablization of serum PSA values during the treatment phase was observed.

The goal of therapeutic cancer vaccines is to “teach” the patient’s own immune system to attack cancer cells while sparing other cells by exposing the immune system to a substance (an antigen) that is as specific to cancer cells as possible, thus inducing an immune response to any cells that present that antigen. The telomerase vaccine being tested at Duke generates cytotoxic T-cells specific for telomerase, and those T-cells then attack cancer cells that express telomerase—while not affecting most normal cells. The Duke clinical trial uses an ex vivo (outside the body) process in which dendritic cells (the most efficient antigen-presenting cells) are isolated from the patient’s blood, pulsed with telomerase RNA, and then used to vaccinate the patient.

This clinical trial is designed to enroll a total of 24 patients with metastatic prostate cancer, 12 of whom receive three weekly vaccinations (low-dose group), and 12 of whom receive six weekly vaccinations (high-dose group). Eighteen patients (all 12 of the low-dose group and six of the high-dose group) have been enrolled and treated so far. None of the patients in either group has shown treatment-related adverse effects to date. As reported by Dr. Vieweg today, the three patients thus far analyzed in the high-dose group all showed cellular immune responses to telomerase, based on tests assessing the generation of telomerase-specific cytotoxic CD-8+ T-lymphocytes, as well as CD-4+ lymphocytes. The immune responses were strong as well as specific: five to 15-fold higher, on average, than the immune responses seen in the low-dose group. These high levels of T-cell responses are comparable to those seen after vaccinations for infectious diseases that result in clearance of the infection. Three of four patients in the high-dose group had elevated levels of cancer cells circulating in their blood before the trial, and those cancer cells were transiently cleared from their blood in two of those three. The level of prostate-specific antigen (PSA) measured in the patients’ blood remained stable in three of three patients in the high-dose group during the treatment phase and for a minimum of eight weeks follow-up.

The new data presented today supplement data that Geron reported in April from the low-dose group. All of those patients showed a significant cellular immune response specific to telomerase. Levels of circulating cancer cells were reduced to normal in six of the eight patients who had significantly elevated levels of cancer cells circulating in their blood before the trial; and for a period of three months after treatment, PSA levels stabilized or declined in all three of the patients who had rising levels of PSA when they entered the study.

“These results confirm our previous findings, ” said Dr. Vieweg. “The experience of these patients gives us confidence that the vaccine can be administered safely, and the data on telomerase-specific immune responses and changes in circulating tumor cells and PSA levels point in the direction of clinically effective anti-tumor immunity. More work needs to be done, of course, and patients need further follow-up, but I am very encouraged by the results so far.”

The ex vivo dendritic cell processing technology used in this clinical trial was developed at Duke by Drs. Eli Gilboa and Johannes Vieweg and their colleagues, and is licensed to Merix Biosciences. Geron and Merix have been collaborating for more than three years on the preclinical and clinical use of telomerase-based vaccines using the Duke technology. 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 as tested in the trial at Duke. The clinical trial is funded by a grant to Duke University from the National Institutes of Health.

“We are pleased by these data which, first of all, continue to show the safety of telomerase vaccination in cancer patients, especially in view of the strong telomerase-specific cytotoxic T-cell responses generated in the vaccinated patients, “ said Thomas B. Okarma, Ph.D., M.D., Geron’s president and chief executive officer. “Moreover, the early effects seen on PSA levels and circulating tumor cells in some of these patients suggests that we are on the right track toward developing a vaccination approach that will prove to be clinically meaningful.”



GERON REPORTS PRESENTATION OF POSITVE RESULTS OF TELOMERASE CANCER VACCINE CLINICAL TRIAL
Menlo Park, CA–June 7, 2004 – Geron Corporation (Nasdaq: GERN) today announced the presentation of new positive results from a Phase I/II clinical trial of its telomerase therapeutic vaccine in metastatic prostate cancer. The presentation was given yesterday at the American Society of Clinical Oncology (ASCO) annual meeting in New Orleans, Louisiana by the principal investigator of the trial, Johannes Vieweg, M.D., Associate Professor of Urology and Associate Professor of Immunology at Duke University Medical Center.

Vaccination Induces Vigorous Immune Responses Without Side Effects

Dr. Vieweg’s presentation summarized the laboratory and clinical findings from the 20 patients who have been enrolled in the trial. Nineteen of the twenty patients responded to the vaccine by generating telomerase specific cytotoxic T-cells. None of the patients experienced any treatment-related side effects. Patients in the high dose group (those receiving 6 weekly injections) responded with a dramatic telomerase-specific T-cell response that increased over the treatment course and peaked 2 to 4 weeks after the final dose. Peak levels of their telomerase-specific T-cells were remarkably high, ranging from 0.9% to 1.8% of the total circulating cytotoxic T-cell pool. Telomerase-specific T-cells were detected for at least 16 weeks after vaccination.

High Dose Patient Group Shows Statistically Significant Increase in PSA Doubling Time

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.


Gruß, greenhorn

[greenhorn1998]

Und hier Produkt Nummer zwei:

Cancer Programs : Telomerase Inhibition


The activation of telomerase is necessary for cancer cells to replicate indefinitely and thereby enable tumor growth and metastasis. One of our strategies for the development of anti-cancer therapies is to inhibit telomerase activity in cancer cells. Inhibiting telomerase activity should result in telomere shortening and therefore cause the aging and death of cancer cells. Recent data show that telomerase can protect tumor cells from genomic instability and cell death, suggesting that inhibiting telomerase can cause a more rapid suppression of tumor growth than predicted by telomere loss alone. Because telomerase is expressed at very low levels, if at all, in most normal cells, the telomerase inhibition therapies described below are not expected to be cytotoxic to normal cells.
We have designed and synthesized a special class of short-chain nucleic acid molecules, known as oligonucleotides, that target the template region, or active site, of telomerase. These oligonucleotides, called GRN163 and GRN163L, have demonstrated highly potent telomerase inhibitory activity at very low concentrations in biochemical assays, various cellular systems, and animal studies. We are now engaged in additional animal toxicology and efficacy studies of these drugs that, if successful, should enable us to file an Investigational New Drug (IND) application to begin human clinical trials.
Our compounds GRN163 and GRN163L are direct enzyme inhibitors, not antisense compounds. They are much smaller (lower molecular weight) than typical antisense compounds or other oligonucleotide drug candidates, and we expect them to be administered either locally or systemically. They do not inhibit other critical nucleic acid-modifying enzymes and do not appear to be toxic to normal cells at concentrations needed to inhibit telomerase in tumor cells. Both compounds use a special thiophosphoramidate chemical backbone, for which we acquired controlling patents in March 2002 from Lynx Therapeutics.
We and our collaborators have so far tested GRN163 in vitro on 13 different cancer cells and demonstrated significant inhibition of telomerase activity in all of them. Research by our collaborators has shown that these compounds inhibit the growth of malignant human glioblastoma (brain cancer) cells, prostate cancer cells, lymphoma, myeloma, hepatocellular carcinoma (liver cancer) and cervical cancer cells in animals.
Intratumoral administration of GRN163 in an animal model of human glioblastoma resulted in complete tumor eradication in five of seven treated rats without any toxicity and significantly extended their survival compared to untreated controls. Intravenous administration of GRN163 in a study of animals bearing disseminated human multiple myeloma substantially reduced tumor growth and resulted in a 50% increase in survival compared to controls. GRN163L is identical in structure to GRN163 except that it has a lipid attached to one end of the molecule, which appears to improve its pharmacokinetics and should make its manufacture more efficient and less expensive. The improved pharmacokinetic characteristics of GRN163L suggest that it should be effective in inhibiting telomerase in tumor cells when administered intermittently (one injection every few days).






GERON REPORTS POSITIVE DATA ON GRN163L, A LIPIDATED TELOMERASE INHIBITOR DRUG FOR THE TREATMENT OF CANCER
Menlo Park, CA – November 20, 2003 – Geron Corporation (Nasdaq: GERN) today reported preclinical data on its lipidated telomerase inhibitor anti-cancer drug candidate, GRN163L. The data, from both in vitro and in vivo studies of GRN163L, were presented on November 18 and 20, at the Workshop on Telomeres and Telomerase: Therapeutic Targets for Cancer and Aging in Madrid, Spain, and at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, Massachusetts. The studies indicated that GRN163L demonstrates enhanced bioavailability and potency, while maintaining high specificity to telomerase, good safety and tolerability, and appropriate stability in both liquid and freeze-dried formulations.

Geron has previously reported on GRN163, an oligonucleotide drug that binds to telomerase with high affinity and specificity, and which potently inhibits telomerase in multiple different cancer cell lines. Treatment with GRN163 induces apoptosis in cancer cells in vitro, and demonstrates substantial anti-tumor efficacy in vivo against multiple tumor types following systemic administration at doses that are very well tolerated.

GRN163L (formerly called GRN719) has the same nucleic acid sequence as GRN163, with the addition of a lipid (a fatty substance) to enhance cellular uptake. The enhancement of cellular uptake means an increase in potency of the drug, which would reduce the doses required to achieve efficacy.

In the studies presented at the meeting, Geron scientists and collaborators assessed inhibition of telomerase in vitro in 12 different tumor cell lines, and found that GRN163L demonstrated 3 to 40-fold greater potency than that of GRN163, without loss of specificity. Importantly, telomerase inhibition in this and other studies was also substantially greater in animals treated in vivo with GRN163L. In vivo pharmacodynamic assessment following intravenous or intraperatoneal administration of GRN163L and GRN163 in mice confirmed that the lipidated compound showed substantially greater suppression of telomerase activity, with sustained telomerase inhibition for at least 3 days following a single dose of GRN163L.

A 14-day multiple ascending-dose toxicity study of parenteral administration of GRN163L in mice demonstrated excellent tolerability at even the highest dose tested. Additionally, a 4-week accelerated stability study of GRN163L demonstrated good physical, chemical and biochemical stability following storage at temperatures ranging from -80 to +20 degrees celsius.

“There are obvious advantages associated with the greater potency of GRN163L, and we are making sure that the lipid modification does not adversely affect any other important parameter of the drug. We are very pleased with the results so far of our testing of GRN163L,” said Thomas B. Okarma, Ph.D., M.D., Geron’s president and chief executive officer. “We are making good progress on advancing our telomerase inhibitor compounds toward clinical development.”

The International Conference on Molecular Targets and Cancer Therapeutics was organized by the American Association for Cancer Research, the National Cancer Institute, and the European Organization for Research and Treatment of Cancer. The Workshop on Telomeres and Telomerase: Therapeutic Targets for Cancer and Aging was organized by the Instituto Juan March de Estudios e Investigationes.

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.


GERON ANNOUNCES NEW DATA ON GRN163L, A TELOMERASE INHIBITOR DRUG FOR CANCER THERAPY
Menlo Park, CA – March 30, 2004 – Geron Corporation (Nasdaq: GERN) announced the presentation of additional data from preclinical studies of GRN163L, a potent and specific telomerase inhibitor, at the American Association for Cancer Research (AACR) Annual Meeting in Orlando, Florida. The results presented confirm and extend the in vitro and in vivo efficacy of GRN163L in solid tumors, specifically liver and ovarian cancer, and report a sensitive, accurate, and reproducible assay for the detection of the drug in human blood.

“We are pleased to be presenting data from these efficacy studies and newly developed analytical methods at AACR,” said Calvin B. Harley, Ph.D., Geron’s chief scientific officer. “We have now collected efficacy data in two types of hematologic tumors (multiple myeloma and lymphoma), and five solid tumors (glioblastoma, hepatoma, and cancer of the cervix, prostate, and ovary). These studies, together with our ongoing safety assessment and drug manufacturing activities, mark our progress towards human clinical trials.”

The first study, conducted by researchers at Memorial Sloan-Kettering Cancer Center in New York in collaboration with Geron scientists, examined the efficacy of GRN163L in human ovarian tumor cell lines. In tissue culture, GRN163L inhibited telomerase in all four tumor lines, and caused telomere loss and cell death in three of the four. In addition, in a mouse model of human ovarian cancer, it was demonstrated that GRN163L inhibited growth in a dose-dependent manner when administered three times per week into the abdominal cavity.

The second set of studies, conducted by researchers at Medical School Hannover in Hannover, Germany in collaboration with Geron scientists, focused on the effect of GRN163L and Geron’s related telomerase inhibitor, GRN163, on human liver cancer (hepatoma) cells. They first reported on the potency of each compound against a panel of tumor lines representing multiple different cancer types in culture. GRN163L was on average about ten times more potent than GRN163 in inhibiting telomerase activity in cultured tumor cells. For two hepatoma lines in the panel, GRN163L was 7 and 18 times more potent.

One of the hepatoma tumor lines, Hep3B, was also studied in an in vivo mouse model of human liver cancer. In the first set of experiments, human hepatoma-bearing animals were dosed Monday-Friday via intraperitoneal (systemic) injection for 4 weeks with control vehicle, GRN163L, or GRN163. In a second set of experiments designed in part to define the minimum effective dose of the drugs, both compounds were administered at lower concentrations and 3-times per week rather than 5-times per week. GRN163L was effective at reducing tumor growth in both sets of experiments, while GRN163 was only effective in the first model system. These experiments are consistent with the earlier observations of increased potency of GRN163L over GRN163 and are supportive of pharmacokinetic data that predicted a more durable effect of GRN163L in tissue compared to GRN163.

The third presentation reported on Geron’s development of a sensitive and specific assay for the detection of GRN163L and GRN163 in human plasma and tissue samples. The assay can measure as low as 0.1 nanogram (less than 1 billionth of a gram) of the drug in a plasma sample, and is suitable for parallel (multi-well, or high-throughput) processing of material. The assay will be an important tool for Geron’s understanding of the relationship between drug levels in the body and drug safety and efficacy in both animal studies and human clinical trials.

Both GRN163L and GRN163 are oligonucleotide drugs that bind to telomerase with high affinity and specificity, and potently inhibit telomerase in cancer cells with little impact on normal cells. They have the same nucleic acid sequence, but GRN163L contains a lipid to enhance cellular uptake. The enhancement increases potency of the drug, reducing the dose requirements to achieve efficacy.


Ist ein bisschen viel zu lesen. Aber vielleicht findet es der eine oder andere ja ganz interessant.

Gruß, greenhorn

[derschweizer]

Hallo Leute,

möchte Euch auf 898572 Nymox (NYMX) aufmerksam machen.

http://www.nymox.com

Das Unternehmen hat sich auf Alzheimer / Prostata Medikamentenentwicklung spezialisiert.
Interessant finde ich die Patent-Situation, sowie die neuen Ansätze der Wirkstoffentwicklung (Alzheimer).

Der Kurs bewegt sich zu unrecht auf 52 W/Tief.
BrauchGeld wird sagen: "Typisch CA Biotech".

viel Spass beim stöbern.

grüße derschweizer

[Neoe]

Was hier sicher nicht fehlen darf:

PBT-2 von Prana:

Marktpotential 5 Milliarden Dollar, einziges Medikament das nachweislich die Fähigkeit besitzen wird, Alzheimer nicht nur für eine gewisse Zeit aufzuhalten, sondern die
Krankheit zurückdrängt (lässt sich jetzt schon sagen, durch die Erfahrungen mit PBT-1).

Beginn der PhaseI in Q1 2005. Es wird nicht lange dauern bis PBT-2 auf der Drugs To Watch-Liste von Forbes erscheint.

[Neoe]

Noch was:

GCS-100LE von Glycogenesis, momentan in PhaseI

Eine der 100 vielversprechendsten Medikamente zur Heilung von Krebs (von R&D Direction ausgezeichnet)
Das Unternehmen macht gerade eine schwierige Phase durch. Bis Anfang 2005 sollten die Weichen gestellt sein. Ist dann alles in Butter wird Glycogenesis sicher sehr interessant werden.

[derschweizer]

@all

Hallo Leute,

ich möchte euch DYAX vorstellen.

http://www.dyax.com

Das Unternehmen entwickelt zur Zeit drei Medikamente in Phase 2 und hält Schlüsselpatente für seine Antikörper, Peptide, kleine Proteine Technologie.
Die Medikamentenanwärter zielen alle auf einen lukrativen Markt ab. Für keine der Indikationen gibt es zur Zeit ein Medikament das Aussicht auf Heilung verspricht.
1.One Pump Open Heart Surgery (CABG)
Blutverlust bei einem Eingriff am offenen Herzen.
2.Hereditary Angioedema (HAE)
Enzymdefekt, der Haut, Schleimhäute und Magen-Darmtrakt befällt (Edeme mit 1-2 ltr. Flüssigkeit und starken begleideten Schmerzattacken)
3.Cystic Fibrosic (CF)
Die Krankheit befällt Lunge und Bauchspeicheldrüse und erschwert dadurch stark die Atmung und die Verdauung.
Die Lebenserwartung liegt bei 30-35 Jahren.
Für HAE und CF besitzt Dyax Orphan Drug Designation

Marketcap ca. 200 Mio.US$
Shares 31,5 Mio.
Cash 62 Mio US$

grüße derschweizer

[Neoe]

Momentan haelt das Glueck die Treue:

GlycoGenesys, Inc. Announces Victory in License Dispute With Former CEO
Thursday November 11, 6:09 pm ET
Arbitrator Affirms Company`s Exclusive Rights to Intellectual Property


BOSTON--(BUSINESS WIRE)--Nov. 11, 2004---GlycoGenesys, Inc. (NASDAQ:GLGS - News), a biotechnology company focused on carbohydrate drug development, today announced that it has received a favorable decision in final and binding arbitration proceedings. The arbitration was brought by the Company against David Platt, its former CEO, who is now CEO of Pro-Pharmaceuticals, Inc. (AMEX:PRW - News).
PUBLICIDAD


Today`s favorable ruling affirms the Company`s exclusive rights to the disputed intellectual property. This intellectual property relates to GCS-100, the Company`s lead drug candidate. The decision in favor of GlycoGenesys is final and binding and is only appealable based on strict and limited grounds. Under today`s ruling Platt, as inventor, continues to prosecute patent applications covered by the license agreement for the benefit of the Company and the Company retains exclusive rights to the technology.

Bradley J Carver, CEO and President of GlycoGenesys, Inc. stated, "The `cloud` that has overshadowed GlycoGenesys` accomplishments and intellectual property this year is now lifted. Our exclusive rights to GCS-100 have been undeniably determined. The value of past and future achievements relating to GCS-100 can now be properly recognized."

Mr. Carver continued, "We are sometimes required, as in this case, to take legal actions to defend and secure what is rightfully ours. This victory is an important milestone and good news for shareholders and employees who stayed the course with us. In accordance with today`s ruling, Platt`s prosecution of the patent applications in question will be solely for the benefit of the Company and this decision leaves no doubt to our rights under the license agreement to develop and commercialize GCS-100."

Legal synopsis of the decision

The arbitrator found that Platt had breached the license agreement by filing a patent application related to those already covered by the agreement without having informed the Company and affirmed the Company`s position that Platt`s subsequent patent application is also covered by the agreement. The arbitrator rejected Platt`s contention that the Company had breached the license agreement and refused to terminate the agreement, as Platt had requested. Instead, the arbitrator found that the Company retained its exclusive rights to the technology in question. The arbitrator allowed Platt to continue prosecuting the patent applications in which he is listed as inventor, finding that Platt had not relinquished an inventor`s right to control prosecution of his applications. Prosecution of the applications is for the benefit of the Company, which retains exclusive rights to develop and commercialize them.


GlycoGenesys, Inc. Claims Rights to Davanat in Lawsuit with Platt and Pro-Pharmaceuticals, Inc.
Thursday November 11, 6:25 pm ET
Company`s Rights to GCS-100 Not In Dispute


...........................................................

BOSTON--(BUSINESS WIRE)--Nov. 11, 2004--GlycoGenesys, Inc., (Nasdaq: GLGS - News), a biotechnology company developing carbohydrate-based drugs, announced earlier today that it was awarded a favorable ruling in the arbitration proceedings brought by the Company against David Platt, its former CEO. With this favorable decision in hand, GlycoGenesys is taking the opportunity to describe the separate litigation with Platt and Pro-Pharmaceuticals, Inc. (AMEX:PRW - News), the company Platt now heads, and its business implications. This separate litigation, regardless of outcome, does not affect our rights to pursue commercialization of GCS-100.
PUBLICIDAD


Bradley J Carver, President and CEO of GlycoGenesys, Inc., said, "With the issuance of the favorable arbitration decision, the outstanding litigation risk and uncertainty relating to GlycoGenesys` intellectual property is clearly resolved. As we move forward, we believe the focus on litigation risks and uncertainties relating to intellectual property will shift to Platt and Pro- Pharmaceuticals, because we are seeking ownership of Davanat®."

Mr. Carver continued, "As previously disclosed, Platt initiated a separate litigation against GlycoGenesys largely in connection with his termination agreement. As part of this litigation, we have filed several counterclaims against Platt and Pro-Pharmaceuticals targeting their core intellectual property including Pro-Pharmaceuticals` lead product, Davanat. We are seeking the assignment of Davanat to GlycoGenesys and to prevent Platt and Pro- Pharmaceuticals from developing and selling polysaccharides to treat cancer. Much as GlycoGenesys has done through the arbitration process, we will pursue this legal action in a manner that minimizes management`s time and is results driven."

"Platt`s claims in the litigation, in which he seeks monetary damages, in our opinion are without merit. Moreover, we believe they represent limited financial exposure to us based on the amount of severance in dispute and the price and volume of our stock following the expiration of his lock-up and his realized proceeds," concluded Mr. Carver.

Litigation

Background:

In May 2000, David Platt signed a termination agreement and agreed not to compete with GlycoGenesys.

In July 2000, Platt incorporated Pro-Pharmaceuticals, Inc., a biotech company to develop carbohydrate-based drugs and drug-delivery products in the field of oncology.

In early 2001, the Company stopped severance payments under the termination agreement because of Platt`s competitive activities with Pro-Pharmaceuticals, as well as other breaches of the termination agreement.

In the fall 2002 through summer 2003, Platt sold shares of GlycoGenesys subject to Rule 144 limitations.

In January 2004, the U.S. Patent and Trademark Office issued to GlycoGenesys U.S. Patent No. 6,680,306 "Method for Enhancing the Effectiveness of Cancer Therapies" covering the use of GCS-100® and other carbohydrates that bind to galectins prior to or in combination with chemotherapy or surgery for the treatment of cancer.

Pro-Pharmaceuticals` lead drug candidate, Davanat®, is a carbohydrate administered in combination with existing chemotherapies to potentially enhance their efficacy and reduce their toxicity. Pro-Pharmaceuticals publicly states that Davanat binds to galectins. Pro-Pharmaceuticals began developing Davanat shortly after David Platt signed a termination agreement with GlycoGenesys.

Lawsuit:

In late January 2004, Platt filed a lawsuit against the Company. In this suit, Platt seeks damages from the Company and certain of its directors for, among other claims:

alleged breach of the termination agreement between the Company and Platt for, among other things, failure to pay Platt severance (net payments of approximately $180,000);
alleged breach of fiduciary duty for failing to release transfer restrictions on his GlycoGenesys stock in an appropriate manner; and
unfair trade practices.
In response to Platt`s lawsuit, GlycoGenesys brought counterclaims against Platt and PRW asserting that:

Platt breached the non-competition provisions of his termination agreement within months of signing it by founding Pro-Pharmaceuticals and targeting carbohydrates to treat cancer;
Platt misappropriated GlycoGenesys` confidential information and used it to help develop Davanat and potentially other Pro-Pharmaceuticals technologies;
Platt and Pro-Pharmaceuticals engaged in business libel by making false statements in press releases and public statements about GlycoGenesys` intellectual property rights in GCS-100;
Platt breached the non-disparagement clause and other provisions set forth in the termination agreement; and
Platt and Pro-Pharmaceuticals both engaged in unfair trade practices.
The Company is seeking damages and permanent injunctive relief including:

an order to assign all rights in Davanat and other Pro-Pharmaceutical`s inventions to GlycoGenesys;
a permanent injunction on Platt and Pro-Pharmaceuticals from developing, selling or using polysaccharide compounds to treat cancer;
a permanent injunction on Platt and Pro-Pharmaceuticals from using proprietary and confidential information of GlycoGenesys;
an injunction preventing Platt from participating in the business of Pro- Pharmaceuticals for 2 years; and
the recovery of all payments made to Platt under the termination agreement as well as associated costs and attorneys fees
GlycoGenesys, Inc.

GlycoGenesys, Inc. is a biotechnology company that develops and licenses products based on glycobiology. The Company`s human therapeutic product GCS-100, a unique compound to treat cancer, has been evaluated in Phase II(a) human clinical trials at low dose levels for both colorectal and pancreatic cancers with stable disease and partial response documented. The Company currently is conducting a Phase I dose escalation trial to evaluate higher dose levels of GCS-100LE, a low ethanol of GCS-100, at Sharp Clinical Oncology Research in San Diego, California. Further studies are planned for the first and second quarter of 2005. Further information is available on GlycoGenesys` web site: www.glycogenesys.com.



Nachboerslich 120% plus

[greenhorn1998]

Hallo zusammen!

Hier die letzten Neuigkeiten zu Glycogenesys.

a)
GlycoGenesys, Inc. Announces Scientific Rational for Developing GCS-100LE for Potential Treatment of Multiple Myeloma at American Society of Hematology Annual Meeting

GCS-100LE overcomes drug resistance of approved therapies and is shown to have synergistic and additive effects in combination with other drugs for treatment of Multiple Myeloma in vitro
BOSTON & SAN DIEGO, Dec 6, 2004 (BUSINESS WIRE) -- GlycoGenesys, Inc., (NASDAQ: GLGS), a biotechnology company focused on carbohydrate drug development, announced today its lead drug candidate, GCS-100LE, was shown in vitro to trigger cell death in multiple myeloma, including cell lines resistant to standard treatments. The data was presented at The American Society of Hematology 46th Annual Meeting and Exposition in a poster session called New Targets and Immune Based Therapy in a presentation entitled "Mitochondria and Caspase-Independent Cell-Death Triggered By GCS-100, a Novel Carbohydrate-Based Therapeutic in Multiple Myeloma (MM) Cells." The poster was presented by Company collaborator, Dr. Dharminder Chauhan, of Dr. Kenneth Anderson`s laboratory at the Medical Oncology Department, Dana Farber Cancer Institute, Boston, Massachusetts.

Highlights of Poster Presentation
GCS-100LE was found to:

Directly target multiple myeloma cells including in their bone marrow microenvironment.

Trigger cell death in multiple myeloma cells resistant to traditional anti-cancer agents including dexamethasone, melphalan, doxorubicin, and Velcade(R), which are commonly used in treatment of multiple myeloma.

Decrease the viability of Velcade-resistant multiple myeloma patient cells.

Inhibit growth and survival of multiple myeloma cells conferred by the bone marrow microenvironment.

Overcome drug-resistance conferred by anti-apoptotic protein Bcl-2 and heat shock protein- 27.

Induces cell death in multiple myeloma without activating known cell death activating pathways, caspases 8, 9,and 3, without significant toxicity against normal peripheral mononuclear cells, suggesting a potentially novel mechanism of action and providing strong rational for combining GCS-100LE with approved agents that activate caspase-dependent cell death.

To have additive and synergistic effects when combined with caspase-activating agents dexamthasone and PK1195, respectively.
These findings lay the framework for clinical evaluation of GCS-100LE either alone or in combination with other therapies to overcome drug resistance and improve patient outcome in multiple myeloma.

Bradley J Carver, President and CEO of GlycoGenesys, noted that "We are very pleased to have this promising data presented at the ASH Annual Meeting by such distinguished clinicians and researchers. As a co-author with my colleagues on this abstract and working closely with Dr.`s Anderson and Chauhan over the last year, we are excited about our plans to enter the clinic in multiple myeloma with GCS-100LE in early 2005 at the Dana Farber Cancer Institute."

The Study
Multiple myeloma cancer cells use normal bone marrow stromal cells and the bone marrow microenvironment to prevent apoptosis (programmed cell death), which allows them to divide and grow abnormally. GCS-100LE works by directly targeting multiple myeloma cells in their bone marrow microenvironment, interfering with their ability to adhere to the bone marrow stromal cells and inhibiting their growth and proliferation, eventually leading to cell-death. GCS-100LE was shown to trigger growth arrest and apoptosis in a number of multiple myeloma cell lines including cell lines resistant to standard treatments such as dexamethasone, melphalan and doxorubicin. In tests with multiple myeloma cells from patients who have had unsuccessful treatment due to drug resistance, GCS-100LE demonstrated similar results, including in cells from patients resistant to bortezomib (Velcade(R)). GCS-100LE was effective against these patient`s cells without significant toxicity to normal peripheral mononuclear cells, which naturally help defend against infections and disease.
In this study, it was shown that GCS-100LE induced apoptosis in multiple myeloma cells through a mitochondria and caspase-independent apoptotic pathway. This provides a rationale for combining it with treatments that work through potentially complimentary apoptotic pathways, including caspase-dependent pathways. For example, in combinatonGCS-100LE, acts synergistically with PK-11195 and additively with dexamethasone.

About Multiple Myeloma
Multiple myeloma (also known as myeloma or plasma cell myeloma) is a progressive hematologic (blood) disease. It is a cancer of the plasma cell, an important part of the immune system that produces immunoglobulins (antibodies) to help fight infection and disease. Hypercalcemia, anemia, renal damage, increased susceptibility to bacterial infection, and impaired production of normal immunoglobulin are common clinical manifestations of multiple myeloma. It is often also characterized by diffuse osteoporosis, usually in the pelvis, spine, ribs, and skull.
The estimated frequency of multiple myeloma is 4-5 new cases per 100,000 persons per year. Accordingly, in the United States 15,270 new cases are expected to be diagnosed in 2004. At present there are approximately 50,000 people in the United States living with multiple myeloma.

About GCS-100LE
GCS-100LE is a novel carbohydrate compound with potential application in solid tumors and bloodborne cancers. Independent research has shown that Galectin-3, a key target of GCS-100, is implicated in several cellular activities. GCS-100 has at least three mechanisms of action: it may induce apoptosis, or programmed cell death; appears to interfere with angiogenesis, the process by which cancer cells recruit a blood supply from the body in order to proliferate; and appears to interfere with a process called cellular adhesion, which plays a key role in metastasis, or the spread of cancer beyond the primary tumor. Galectin-3 has high expression in many cancers, but not in normal cells, conferring broad potential applications for GCS-100 in solid and blood-borne cancers. GCS-100 has been evaluated at lower dose levels in Phase II(a) clinical trials for colorectal and pancreatic cancer. GCS-100LE, a low ethanol formulation, is currently in a dose escalation Phase I trial for solid tumors with Phase I and II clinical trials for multiple myeloma planned to begin in 2005.

About GlycoGenesys, Inc.
GlycoGenesys, Inc. is a biotechnology company that develops and licenses products based on glycobiology. The Company`s cancer drug candidate GCS-100LE, a unique compound to treat cancer, has been evaluated in previous human clinical trials at low dose levels in patients with colorectal, pancreatic and other types of solid tumor cancers with stable disease and partial response documented. The Company currently is conducting a Phase I dose escalation trial to evaluate higher dose levels of GCS-100LE, a low ethanol formulation of GCS-100LE, at Sharp Clinical Oncology Research in San Diego, California. Further studies are planned for the first and second quarter of 2005. Further information is available on GlycoGenesys` web site: www.glycogenesys.com.


b)
New In Vitro Study of GlycoGenesys` GCS-100LE Yields Promising Data in Chronic Lymphocytic Leukemia and other B-cell Cancers

Data Presented at American Society of Hematology Annual Meeting
BOSTON & SAN DIEGO--(BUSINESS WIRE)--Dec. 7, 2004-- GlycoGenesys, Inc., (Nasdaq: GLGS), a biotechnology company focused on carbohydrate-based drug development, announced today that an in vitro study showed for the first time that its lead drug candidate, GCS-100LE, triggered cell death in both B-cell malignant cell lines and primary cancer cells taken from patients with chronic lymphocytic leukemia (CLL). GCS-100LE, currently in a Phase I dose escalation trial for solid tumors, is a novel carbohydrate-based compound being developed for the treatment of solid tumors and multiple myeloma. Data from the new study was presented last evening by world-renowned cancer researcher and GlycoGenesys collaborator, Dr. Finbarr E. Cotter of Barts School of Medicine, London, at the American Society of Hematology (ASH) 46th Annual Meeting and Exposition in a poster session on Lymphoma Therapy - New Biologic Agents. The poster was titled "GCS-100, a Galectin 3 Antagonist, Is a Novel Caspase-9 Apoptosis Activating Agent for the Treatment of Indolent B-Cell Malignancies."

Dr. Cotter`s Poster Presentation Highlights

GCS-100LE was found to:

Induce significant apoptosis (cell death) in both malignant B-cell lines and in primary patient chronic lymphocytic leukemia cells in vitro with minimal effect against normal B-cells and stem cell cultures.

Greatly enhance the apoptotic effect of chemotherapy at low doses, even in the presence of high levels of anti-apoptotic proteins such as Bcl-2.

Induce cell death in B-cell malignancies including chronic lymphocytic leukemia via caspase-9, a known apoptotic pathway utilized by approved chemotherapy agents. Activation of caspase-9 has been shown to predict a good anti-cancer response in B-cell malignancies.
These findings lay the framework for clinical evaluation of GCS-100LE in B-cell malignancies, especially for potential treatment of chronic lymphocytic leukemia.

The Study
The study investigated the mechanism by which GCS-100LE induces apoptosis (programmed cell death) in indolent B-cell lymphomas. It found that GCS-100LE induced apoptosis in malignant cell lines as well as in primary cells from patients with chronic lymphocytic leukemia with minimal effect on normal B cells. Notably, low doses of GCS-100LE significantly enhanced the effect of chemotherapy in these cancer cells. GCS-100LE was found to induce a specific apoptotic pathway, the mitochondrial caspase-9 pathway. The apoptotic effect of GCS-100LE occurred even in the presence of the protein Bcl-2, a natural inhibitor of cell death, which confers resistance to widely used chemotherapy drugs in several cancers. GCS-100LE has been previously shown to bind to Galectin-3, a protein that generally has a higher expression in B-cell cancers. This may be the cause of GCS-100LE`s targeting of malignant B-cells.

Dr. Finbarr Cotter, GlycoGenesys` collaborator and primary author of the study abstract said, "Our recent study shows for the first time that GCS-100LE has strong activity against primary cancer cells taken from patients with chronic lymphocytic leukemia. In these primary cells and in other B-cell cancer cell lines, GCS-100LE works through a specific caspase-dependent apoptotic pathway. Moreover, other studies have shown that GCS-100LE can activate additional beneficial anti-cancer mechanisms. These attributes of GCS-100LE suggest its application in several different types of cancer and its combination with chemotherapeutic agents that work through complementary pathways for a potential synergistic or additive therapeutic effect. I am keen to commence clinical studies based on this preclinical work."

Bradley J Carver, President and CEO of GlycoGenesys, a secondary author of the study abstract, further commented, "Our poster presentations at this year`s annual meeting of the American Society of Hematology underscore the clinical rationale and versatility of GCS-100LE to be developed for potential treatment of several bloodborne cancers. We are encouraged by Dr. Cotter`s recent findings. They provide solid scientific rationale for expanding the clinical development of GCS-100LE beyond our current programs in solid tumor and multiple myeloma.

About Indolent B-cell Malignancies
In the U.S., over 320,000 people are estimated to have some form of B-cell malignancy and each year approximately 55,000 new cases and 20,000 deaths occur from these cancers. Between 80% and 85% of non-Hodgkin`s lymphomas are of B-cell origin. Indolent B-cell malignancies include chronic lymphocytic leukemia, follicular lymphoma and B-cell non-Hodgkin`s lymphoma as well as other lymphomas. They are low-grade or slow-growing lymphomas that permit long survival periods but are continuously recurring and virtually incurable in advanced stages. Current treatment options are characterized by low-cure rates due to the slow-growing nature of these lymphomas. Patients without symptoms are monitored closely for development of symptoms including tumor masses and major organ involvement. At such times, treatment is started.

About GCS-100LE
GCS-100LE is a novel carbohydrate compound with potential application in solid tumors and bloodborne cancers. Independent research has shown that Galectin-3, a key target of GCS-100LE is implicated in several cellular activities. GCS-100LE has at least three mechanisms of action: it may induce apoptosis, or programmed cell death; appears to interfere with angiogenesis, the process by which cancer cells recruit a blood supply from the body in order to proliferate; and appears to interfere with a process called cellular adhesion, which plays a key role in metastasis, or the spread of cancer beyond the primary tumor. Galectin-3 has high expression in many cancers, but not in normal cells, conferring broad potential applications for GCS-100LE in solid and bloodborne cancers. GCS-100 has been evaluated at low dose levels in previous clinical trials for patients with colorectal, pancreatic and other types of solid tumors. GCS-100LE, a low ethanol formulation, is currently in a dose escalation Phase I trial for solid tumors with Phase I and II clinical trials for multiple myeloma planned in 2005.

About GlycoGenesys, Inc.
GlycoGenesys, Inc. is a biotechnology company that develops and licenses compounds based on glycobiology. The Company`s drug candidate GCS-100, a unique compound to treat cancer, has been evaluated in previous clinical trials at low dose levels in patients with colorectal, pancreatic and other solid tumors with stable disease and partial response documented. The Company currently is conducting a Phase I dose escalation trial to evaluate higher dose levels of GCS-100LE, a low ethanol formulation of GCS-100, at Sharp Clinical Oncology Research in San Diego, California. Further studies are planned for the first and second quarter of 2005. Further information is available on GlycoGenesys` web site: www.glycogenesys.com.


Ich finde das Unternehmen sehr interessant, trotz der starken Fokussierung auf GCS-100. Was haltet ihr von Glycogenesys? Kurz- und langfristig? Würde mich über Meinungen freuen.

Gruß, greenhorn