I attended the stockholders meeting today. In reviewing my notes (which I didn't get around to publishing here) from last year's meeting, I was struck by how similar this meeting was to last year's. My first observation from a year ago read: <<Thomas Okarma arrived at least 15 minutes early. He schmoozed just a little with one or two people he happened to recognize. Then, for probably 10 minutes, he stood alone at the podium, waiting for the clock to strike 8:30. Alex Barkas (Chairman) and David Greenwood (Exec VP) sat at the front table. All the other officers sat over to the far left in a reserve phalanx.>> Ditto this year.
I think a few more stockholders attended this year. I counted about 35 -- that's in addition to Geron staff, officers, and Board members.
A year ago Okarma said he hoped to have hESCs in a clinical trial sometime in 2006. Today he said he hopes to have hESCs in a clinical trial sometime in 2007. sigh.
The one excellent area of progress seemed to be in the Hong Kong JV to develop a telomerase activator drug for treating HIV/AIDS. AIDS eventually wears out the immune system. The telomeres of the lymphocytes get shorter and shorter under the stress of trying to fight off the HIV infection. Okarma said he hopes to start a clinical trial of Geron's telomerase activator drug, TAT002, "soon." He is currently planning to conduct the trial in California, but he hasn't ruled out doing it in Asia -- either instead of or in addition to California.
The other new development that Okarma seemed particularly excited about was evidence that GRN163L targets the cancer stem cells.
I brought my laptop and took extensive notes of Okarma's presentation. Here they are:
· Next 10Q will be filed around August 9th.
· The real issue is to segue from R&D to product development. Well on the way to doing that. 70% of resources being devoted to that effort.
· GRN163L – Telomerase inhibitor drug. Inhibits the enzyme telomerase. GRN163L binds tightly to telomerase active site. It inhibits Telomerase activity. Prevents Telomerase binding to Telomere.
· Nearly all cancers succumb to GRN163L. What is new is that GRN163L now appears to be active against cancer stem cells, a quiescent cell responsible for clinical relapse. GRN163L targets the cancer stem cell. An article will be published in Nature shortly. The study involved Myeloma cells. This augurs well for the upcoming trials, especially the CLL trial.
· CLL trial – give drug once a week for at least 8 weekly dosing cycles. List of parameters to be measured in this trial is long. Looking at lots of data and evidence re how the body handles the drug and how it affects cancer cells.
· By the end of the CLL trial, we should understand how the drug operates as a single agent in the blood of a patient.
· There will also be an infusion duration diminution trial.
· Expect to have early presentation by year-end. Scheduled to present at ASH annual meeting.
· There is also a rationale for using GRN163L in combo drug treatment. Animal models are providing interesting hints re synergy when GRN163L combined with Velcade or Taxol. In a mouse model of ovarian cancer, combining GRN163L with Taxol yielded even better results than with GRN163L as a single agent. The slide Okarma showed us gave a dramatic visual demonstration of those results.
· GRNVAC1. Telomerase RNA-Pulsed dendritic cells. A universal therapeutic cancer vaccine. CD8 and CD4 T-cell lymphocytes are produced to kill cells expressing Telomerase (i.e., cancer cells).
· Completed Phase 1 trial of GRNVAC1 in Prostate Cancer. Significant impact on circulating tumor cells and PSA doubling times. PSA doubling time went from 2.9 to 100, which Okarma characterized as nearly “stable” disease.
· Merck collaboration designed to combine Geron’s and Merck’s vaccine technologies (ongoing in animals). Merck also licenses Telomerase-based non-dendritic cell vaccines.
· Next steps: need data on Merck’s DNA plasmid platform studies and adenovirus platform studies. Okarma said he was very pleased with the Merck collaboration and how it is going.
· Boost strategy. Subjects boosted biweekly. Merck was impressed by the magnitude of the immune response. It appears that the immune response can be maintained indefinitely with booster shots.
· GRNVAC1 closed production System. This closed system for producing GRNVAC1 will dramatically reduce the cost of production. Hope to introduce this system into the protocol next year.
· TAT002 (TAT002) Telomerase activator drug. Focus on telomere shortening and senescence. Looking for small molecule to up regulate Telomerase. Discovered and named TAT002 a lead compound pursuant to a program funded by a JV with a Hong Kong company. Target is HIV AIDS. Telomere mediated senescence is involved in aging lymphocytes. Use Telomerase to restore Lymphocyte activity against HIV AIDS virus. Revive the immune system weakened by AIDS.
· In vitro studies show that HIV virus production is inhibited when TAT002 used to revive lymphocytes.
· TAT002 is a small molecule derived from a root grown in Asia.
· Hope to file IND in HIV/AIDS in 2007. Also exploring use of TAT002 in liver disease models, stroke and myocardial infarction models.
· hESCs
· Geron has derived eight differentiated therapeutic cell types from hESCs
· Two lines of hESCs are fully qualified for human use.
· hESC therapy is the only stem cell therapy that enables a product-based business model. Other stem cells too expensive to duplicate.
· hESCs production in bulk is economic.
· GRNOPC1 for treating spinal cord injury. GRNOPC1 allows mylenation once again to occur. One glial cell will mylenate multiple axons in its vicinity.
· Will begin with Thoracic complete lesions. Ascending toxicity would not have much clinical impact upon a patient suffering a complete lesion in the Thoracic areas of the spine. By contrast, were GRNOPC1 to cause toxicity when treating a lesion in the cervical area of the spine, the consequences could be life threatening. So Thoracic lesions are the better choice for a Phase I trial, even though Thoracic lesions are become less and less common, due in part to air bags.
· Hope for IND next year.
· Other hESCs cell types under development include Cardiomyocytes for heart attack victims and islet cells for treating diabetes. Proof of concept has already been established in using islet cells to treat diabetes.
· 12-month milestones include, inter alia, presenting early clinical data from GRN163L trials, initiate large animal studies on hESC cardiomyocytes, and initiating “soon” the HIV/AIDS study. (my notes appear to be somewhat inconsistent, in that I sometimes quote Okarma as saying that he hopes to start the HIV/AIDS study in 2007 and other times I quote him as saying that he hopes to start it “soon,” but perhaps 8-9 months means “soon” in his vocabulary).
Q&A
· Still need to know the FDA’s view of preclinical package for GRNOPC1. Expect to put the product into the clinic in 2007.
· The prostate cancer trial was not designed to look at survival. The patients were in very advanced stages of the disease.
· HIV/AIDS trial is planned to be done in California. But Geron may also or instead do it in Asia.
· Tumor cells have very short telomeres, so they are very Telomerase dependent.
· Merck acquired its Adenovirus platform acquired from Vical. Merck has licensed Geron technology in connection with Merck’s development of that platform.
· CEGE is dealing with an oncolytic virus; one that contains a telomerase promoter licensed from Geron. CEGE is fast-tracking one of its cancer vaccines but is slow-tracking the oncolytic virus platform.
Marc |
