West Coast Editor

Geron Corp. teamed up with the Biotechnology Research Corp. (BRC) in Hong Kong to form a new, jointly owned overseas company, TA Therapeutics Ltd., which aims to develop telomerase activator drug candidates, with two in the preclinical stages.

"I can tell you that the principal amount of funding is coming from the Hong Kong side, and the initial capitalization is sufficient to get to the answer on these two compounds," said David Greenwood, chief financial officer of Menlo Park, Calif.-based Geron.

The company's stock (NASDAQ:GERN) closed Wednesday at $7.41, up 49 cents.

BRC - which is providing scientific leadership, a research team, capital and laboratory facilities for the effort - was established by Geron's research partner, the Hong Kong University of Science and Technology (HKUST). Geron is contributing an undisclosed amount of capital, scientific leadership, development expertise and intellectual property.

"We're not going to put a permanent team of Geron scientists in Hong Kong," Greenwood said. "We'll be frequent visitors."

Basing research on existing findings that activating telomerase can restore function in some aged or diseased tissues, TA Therapeutics aims to advance work already done by Geron with HKUST.

"It's a three-year work plan, so we don't have to go back and get more funding every six months," Greenwood told BioWorld Today. "We're going to work with these compounds in a number of animal systems."

Using telomerase gene transfer as a model, Geron has proved the biological utility of telomerase activation in more than 20 different human cell types.

Both of telomerase's two core subunits - hTR, the human telomerase RNA component, and hTERT, the human telomerase reverse transcriptase - have been cloned by Geron and its collaborators. Loss of telomere function on one or a few chromosomes triggers a response associated with damaged DNA, leading to loss of normal cell function, division capacity, and/or cell death, also known as "replicative senescence."

In its telomerase inhibition program, the company is shooting to finish preclinical work early this year on the oligonucleotide GRN163L, and a telomerase therapeutic vaccine for metastatic prostate cancer is in an investigator-sponsored Phase I/II study at Duke University Medical Center. Several smaller Phase I/II trials also are under way at Duke in the prostate cancer indication, with the company expecting to file an investigational new drug application for a Phase II study of the vaccine when the Phase I/II optimization trials finish.

"We've reported the initial data from the Phase I/II in prostate, and we're doing a second round now to tweak the system, make it more efficient," Greenwood said. More results will be reported later this year.

GRN163L and another oligonucleotide, GRN163, are direct enzyme inhibitors, not antisense compounds, with a lower molecular weight than typical antisense compounds. Both use a special thiophosphoramidate chemical backbone, for which Geron acquired key patents in March 2002 from Lynx Therapeutics Inc., of Hayward, Calif.

Early stage GRN163 has been tested in vitro on 13 different cancer cells and yielded significant inhibition of telomerase activity in all of them.

Geron's nuclear transfer technology gained the firm a headline-making deal late last year. Revivicor Inc. bought license rights that allow the transgenic pig firm to use the approach for animal cloning and making human proteins such as polyclonal antibodies for vaccines from animal blood. Revivicor's parent company was the now-defunct Edinburgh, UK-based PPL Therapeutics plc. (See BioWorld Today, Nov. 12, 2004.)