Editor

Geron Corp.'s steady news trickle this summer presages a stronger flow as the year goes on, and an "analyst day" last week got a hosted peek into what's ahead next year, leaving Geron watchers optimistic but reservedly so.

The summer so far has provided plenty to talk about.

This month, the company started a Phase I/II trial with GRNVAC1, its telomerase cancer vaccine, trying the drug in patients with completely remitted acute myelogenous leukemia. Geron makes GRNVAC1 from the patient's blood, using a process that generates dendritic cells containing RNA coding for the protein component of telomerase.

Enrollment in the GRNVAC1 AML trial probably won't finish until the second half of next year, though, and the market is not huge. The American Cancer Society said about 11,900 new cases of the disease surface annually. Only about half of those make it to remission, and the five-year survival rates for adults under 60 years of age go as high as 30 percent, but the rate plummets to 10 percent in seniors.

Geron targets telomerase because as much as 90 percent of cancer cells apparently depend on it to keep growing and spread, though skeptics note the enzyme might be a marker of cancer, rather than a cause.

"We view the project as high risk," wrote Joel Sendek of Lazard Capital Markets in a research report, since "no clear link exists" between prospective alterations of telomerase - either inhibiting the enzyme, as in the cancer programs, or stimulating it, as in the HIV program - and improved outcomes.

Also in July, Geron kicked off a Phase I/II trial of its lead candidate, the second-generation telomerase inhibitor GRN163L, in patients with advanced non-small-cell lung cancer. The main goal is to determine safety and find the maximum tolerated dose (MTD) of GRN163L when given intravenously in combination with a paclitaxel/carboplatin regimen.

The NSCLC study represents the first time in the clinic for GRN163L combined with chemo - a key step because, if it fails, other planned combo trials could be in jeopardy, along with Geron's strategy with the compound. On the other hand, if the trial succeeds and scientists come away with a reliable MTD, a Phase II study could start as early as the second half of next year.

June brought three morsels from the company. First, Geron presented research at the Federation of Clinical Immunology Societies meeting in San Diego showing that its embryonic stem cell treatment for spinal cord injuries, GRNOPC1, is tolerated by the human immune system. An investigational new drug application is expected later this year.

The next day, Geron had more word on GRN163L, saying the cancer drug has shown good pharmacokinetics and tolerability in an ongoing Phase I/II trial involving patients with chronic lymphocytic leukemia. Those results were disclosed at the Pan Pacific Lymphoma Conference in Maui, Hawaii.

Later in June, the company reported a non-clinic based development: Geron boosted its stake in a joint venture with Hong Kong-based Biotechnology Research Corp., called TA Therapeutics Ltd., from 50 percent ownership to 75 percent. TAT is working on telomerase activators, and is making preclinical progress toward filing an investigational NDA for an HIV/AIDS therapy.

Most eyes are on the cancer compound GRN163L, described as a 13-mer oligonucleotide with a thiophosphoramidate chemical backbone - so it hybridizes directly with RNA of the active site on the telomerase enzyme - and a lipid molecule attached to boost bioavailability and make possible once-weekly dosing. Geron says the drug could work as a sensitizer to chemotherapy and as maintenance therapy, and researchers are exploring it as a single agent in blood cancers and in combination with standards of care in solid tumors.

The Phase I/II CLL trial gives intravenous, escalating amounts of the drug - from 20mg/kg to 540 mg/kg - in an effort to figure out the MTD. So far, one patient in each cohort ended up with Grade 3 and Grade 4 thrombocytopenia, but one patient in the fourth cohort achieved stable disease after only two cycles of treatment. Another patient apparently came down with tumor lysis syndrome, but what caused the condition isn't clear.

Another Phase I/II trial, this one by the University of Chicago Cancer Research Center, is trying GRN163L against solid tumors, raising the once-weekly IV doses from 0.4mg/kg to 15 mg/kg in a cycle that lasts four weeks. So far, no dose-limiting toxicities have appeared.

There's yet another Phase I/II GRN163L study gearing up, and it's going after the indication which could provide the compound's best shot at approval: multiple myeloma, in which Geron disclosed encouraging preclinical data at the American Society of Hematology meeting late last year. Analysts expect the new trial, testing GRN163L as a single agent in MM, could start as early as the third quarter of this year, with data in the third quarter of next.

Also in MM, Geron is expected to kick off in early 2008 a Phase I/II study with GRN163L and chemo. If earlier data support the move, a Phase III single-agent trial could begin even before the Phase I/II study finishes - as early as the end of 2008 or the first part of 2009. But the hurdle for efficacy in MM is high. Millennium Pharmaceuticals Inc. won approval for Velcade (bortezomib) with overall response rates as high as 60 percent, in patients who had been through plenty of other therapies first.

With data flowing, Geron's likely to have a busy year in 2008. And, before the end of 2007, Merck & Co. Inc., which entered a license deal with Geron in 2005, is expected to decide whether it will partner GRNVAC1 or develop an in-house telomerase vaccine that's been in the works. Geron's stock, prone to volatility because of the political situation around stem cells, was trading in the $7.50 area late last week, with a 52-week low of just under $6, and a high of $10.