Nigel,
Have you done any digging yourself or just making the suggestion? I'd be pleased to know anything you've got.
In addition to the hepatocyte news, Duke collaborators are presenting PI results of a vaccine at AACR. The abstract has been out for a while, of course, and it is unlikely that there is anything substantial that the investigators can add . . .
>>Vaccination of patients with hormone-refractory prostate cancer using telomerase RNA transfected DC: results from a Phase I Clinical Trial
Zhen Su, Philipp Dahm, Jens Dannull, Christian deBeck, Alfonso Crisci, Doris Coleman, Donna Yancey, John Higgins, Donna Niedzwiecki, Eli Gilboa, Johannes W. Vieweg, Duke University Medical Center, Durham, NC.
hTERT, human telomerase reverse transcriptase, is overexpressed in 90% of all solid tumors and therefore represents a prime target for cancer immunotherapy. Recently, we have shown that telomerase RNA-transfected DC represent potent stimulators of telomerase-specific T cells and anti-tumor activity in vitro and in in vivo models. Based on these observations, we conducted a phase I clinical trial evaluating this strategy in patients with hormone-refractory prostate cancer. Autologous dendritic cells were generated from monocytic precursors by cultivation in X-VIVO 15 medium supplemented with GM-CSF
(800U/ml) and IL-4 (500U/ml) for 6 days. DC were transfected via electroporation with in vitro transcribed hTERT RNA and terminally matured in the presence of TNF-?, IL-1?, IL-6, and PGE-2 for 24 hours. DC were administered by three intradermal injection of 1x107 cells in weekly intervals. In parallel, a cohort of patients received DC transfected with an RNA encoding a chimeric hTERT/LAMP protein allowing for concomitant induction of telomerase-specific CD8+and CD4+ T cell responses. Pre and post vaccination peripheral blood samples were analyzed for T-cell reactivity and patients were followed clinically. Results from 11 vaccinated patients enrolled thus far, revealed no dose-limiting or adverse effects in all patients enrolled. Furthermore, rapid induction of hTERT-specific CTL and helper T cells was observed after vaccination. DC therapy was further associated with a significant decrease (³20%) in PSA velocity after vaccination. In subjects, we observed disease stabilization according to NCI response criteria. This stabilization, however, was only observed in subjects enrolled in the hTERT/LAMP group, indicating that the induction of a concomitant CD4+ T cell response may augment the therapeutic potential of DC-based vaccination.The demonstration of vaccine safety, successful in vivo induction of hTERT-specific immunity, and impact on surrogate clinical endpoints provides a scientific rationale for further clinical investigation of telomerase RNA-transfected DC in the treatment of hormone-refractory prostate cancer.<<
It is partnered with Merix, which licensed the stem cell portion of the technique from Dr. Gilboa:
>>MENLO PARK, CA and Research Triangle Park, NC —August 29, 2000— Geron Corporation (Nasdaq: GERN) and Merix Bioscience, Inc. announced today that researchers at Duke University Medical Center have demonstrated the use of telomerase as an antigen to stimulate an immune response that inhibits tumor growth in animals and kills human tumor cells in vitro. The research, published in the September 2000 issue of Nature Medicine, shows that RNA encoding the catalytic reverse transcriptase protein component of telomerase (TERT RNA), when introduced into dendritic cells, can stimulate the immune system to recognize and destroy telomerase-positive cancer cells. Geron and Merix also announced a collaboration to develop the telomerase-based cancer immunotherapy for clinical and commercial applications.
Eli Gilboa, Ph.D. and his colleagues at Duke developed the process of modifying dendritic cells ex vivo with RNA encoding tumor antigens as an immunotherapy against cancer. Dr. Gilboa, Dr. Johannes Vieweg and colleagues have now shown that this immunization strategy can be used to stimulate the body’s immune system to kill telomerase-positive cancer cells. In this system, TERT RNA is introduced into dendritic cells ex vivo in tissue culture. Upon immunization, the TERT RNA-modified dendritic cells educate specialized killer cells known as cytotoxic T lymphocytes (CTLs) to recognize and destroy cancer cells expressing telomerase.
The research, performed by the Duke scientists in collaboration with scientists at Geron, takes advantage of the fact that telomerase is abnormally activated in most human cancers. Telomerase is detected in greater than 80% of human tumor samples tested, including those of breast, lung, colon, prostate and hematologic origin.
Study Results
In the reported studies, mouse TERT RNA-modified dendritic cells generated an in vivo immune response in mice that was effective in inhibiting the growth of breast, melanoma, and bladder cancer tumors.
The method was also tested in vitro with human cells obtained from patients with renal and prostate carcinomas. Human TERT (hTERT) RNA was introduced into dendritic cells which induced CTL responses that recognized and killed the patients’ tumor targets in culture.
“The experimental results are important,” commented Tom Okarma, Ph.D., M. D., president and chief executive officer of Geron. “Telomerase is universally present in cancer cells. Therefore, development of hTERT RNA as an antigen to elicit an immune response against a broad range of tumor types, either alone or in combination with other antigens, would represent a significant advance in cancer therapy.”
“We are very pleased with the study results,” added Dr. Gilboa. “The next steps are to conduct thorough preclinical safety studies and assess the clinical potential of this method.”
Geron and Merix Collaboration
Geron and Merix will collaborate to assess the clinical and commercial potential of hTERT RNA as an antigen for cancer immunotherapy using Merix’s delivery system. Each company brings unique proprietary assets to the collaboration. Geron has expertise and proprietary rights in the field of telomerase. Merix holds an exclusive license from Duke University for the ex vivo RNA-modified antigen-presenting cell (i.e., dendritic cell) technology developed by Dr. Gilboa. In addition, Merix, through its collaboration with Gilboa, has access to ex vivo dendritic cell processing expertise for production of the modified cells and immunological assay technologies to facilitate monitoring of a patient’s immune response to treatment. The combination of the companies’ technologies will allow Geron and Merix to jointly advance the development of this cancer immunotherapy platform.
Under the terms of the collaboration, Geron will sponsor preclinical studies at Duke to confirm the safety and efficacy of hTERT RNA-modified dendritic cells to mediate immune responses against tumors. Studies will be performed in parallel by Merix. Geron and Merix will jointly determine the clinical development plan for the combined technology platform. Financial terms of the agreement were not disclosed.
“This collaboration allows both companies to leverage technologies and resources to establish hTERT RNA as a safe and effective antigen in cancer immunotherapy,” stated David Greenwood, senior vice president of corporate development and chief financial officer of Geron. “We can then proceed directly to human clinical development.”
“Human telomerase-encoding RNA is an exciting antigen to bring together with our ex vivo RNA-modified dendritic cell technology platform,” added John Irick, executive vice president of Merix. “This collaboration enables a focused effort to accelerate the potential realization of a new cancer therapy.” <<
Geron is presenting preclinical data for GRN163, too, but IND is not until the fourth quarter of this year:
messages.yahoo.com
Yes, the good news appears to be mostly priced in. They're going to have to finance somehow, and I doubt they'll do it on PI or preclinical results. The only recent example I can think of recently is Kosan, and look what happened to that one (sheesh!). Convert and warrant holders, if they hedged, are sitting on nice profit if they sold short shortly after the deal was done, but covering in the open market will be preferable to converting now. So while the short interest is likely partly due to such hedging, the squeeze mode is still in effect until much higher prices or an amendment, whichever comes first.
As such, there two opportunities to go short GERN:
1) Right about now, with an entry determined by technicals, as fundamental good news appears to be done.
2) If and when the next amendment of convert or warrant terms shows up.
It would seem sensible to start with a half position and add when one of three conditions occurs: 1) the next resistance level stops it; 2) it breaks near term support; 3) the terms get amended.
Thoughts anyone?
Cheers, Tuck |
