West Coast Editor

Don't draw a line through Genta Inc. just yet.

Last week, having lost its big pharma partner Aventis SA after mixed results with its lead drug, Genasense (oblimersen sodium), Genta recorded its second clear failure, this time in multiple myeloma. (See BioWorld Today, Nov. 30, 2004.)

But the Berkeley Heights, N.J.-based company is not giving up, disclosing Friday that it added to its pipeline - some would say created one - by acquiring worldwide rights from Temple University to an antisense drug called LR3001 that targets the c-myb gene, involved in the regulation of cancer cells.

Genta's stock (NASDAQ:GNTA) closed Friday at $1.38, up 9 cents, a far cry from its 52-week high of $16.65.

"The timing is good," said Bennett Weintraub, analyst with Hibernia Southcoast Capital in New Orleans. "They're saying, We're still a company, even if we don't have Genasense.' It will help them do some fund raising - if that's what they have to do - early next year."

The compound has been tested in two Phase I trials at the University of Pennsylvania in patients with drug-resistant myeloid leukemia, and a request has been submitted to the FDA granting orphan drug status to LR3001 as a therapy for chronic myelocytic leukemia.

"I would say the addressable market is at most $100 million, and the drug is at least five years away from the market," Weintraub said, with "all the caveats" that antisense brings.

C-myb is a protein that binds DNA and acts as a transcription factor. Genes up-regulated by c-myb include Bcl-2 (which Genasense targets), Bcl-XL, c-myc, cyclin A1, cyclin D1, cdc2 and COX2. The overexpression of c-myb is known to promote proliferation and decrease the rate of apoptosis.

Sites where c-myb is expressed include early blood cells and neoplastic diseases such as cancers of the breast, pancreas and colon, as well as malignant melanoma and neuroblastoma. Temple's researchers published a paper this fall on c-myb in the Proceedings of the National Academy of Sciences.

"There are a lot of antisense constructs like this being tested out there," Weintraub noted.

Genta also said it would host a conference call and webcast Tuesday to discuss corporate plans and data presented at the meeting of the American Society of Hematology, which began over the weekend in San Diego.

"The abstracts [for Genta's presentations] we've had for a while and there's nothing too outstanding," Weintraub said. A possible exception is detailed news expected with regard to Genasense in the chronic lymphocytic leukemia (CLL) trial, not in the abstract book.

"We know it hit its primary endpoint [of complete or nodular primary remission] but didn't extend survival, and there were some serious adversities," Weintraub said. "We'll get an idea of what the risk-benefit ratio of that drug is, and maybe we'll get an update on the survival data."

But tumor shrinkage in CLL is "not terribly well correlated with survival," he pointed out, and Wall Street's expectations are low. It was the CLL trial results that caused Aventis, part of Paris-based Sanofi-Aventis Group, to pull out of the Genta deal.

"I don't mean to be a wet blanket, but I don't have much hope for Genasense," Weintraub said, noting that the firm is starting over again with an early stage drug.

"What we'd really like to see them do is merge with some other companies that also have some good things in this area and make a go of it," he said. "Just because Genasense doesn't work doesn't mean Bcl-2 is a bad target."

Weintraub had no immediate candidates to name as Genta's merger partner.

"I don't know who the perfect fit would be," he said. "I suppose you just want somebody with cash and infrastructure because Genta's had to close down a lot of its own. The question is then what does Genta bring to the table? They have a bunch of lawsuits."

Shareholder litigation relates to a dark day in May when an FDA advisory panel spurned Genasense for advanced melanoma and the company withdrew its new drug application. The same month, Genta reduced its work force by half to conserve cash. (See BioWorld Today, May 4, 2004.)

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