About four months after restructuring and laying off 40 percent of its work force, Isis Pharmaceuticals Inc. has penned an agreement with Pfizer Inc. to identify second-generation antisense drugs to treat ophthalmic disease.

Carlsbad, Calif.-based Isis expects to receive a $1 million technology access fee, as well as research funding and milestone payments. It also will receive royalties on any commercialized drugs that result.

"Part of the Isis strategy is to find marketing partners for our drugs, and this is a program where we felt Pfizer was one of the world leaders in ophthalmic diseases," said Frank Bennett, Isis' vice president of antisense research. "They were a natural choice."

The parties will use Isis' second-generation antisense platform to identify drugs against targets selected by New York-based Pfizer. Pfizer will cover all worldwide clinical development and commercialization responsibilities. Isis' stock (NASDAQ:ISIS) climbed 15.3 percent Tuesday, or 45 cents, to close at $3.39.

While the companies initially will focus on ophthalmic disease, Pfizer has the right to develop the antisense drugs identified for all human health indications.

"One of the areas that we're considering working on would be drugs that could treat macular degeneration," Bennett told BioWorld Today. "You could also consider using those same drugs for treating abnormal blood vessel growth that occurs in cancer."

Isis has one antisense drug on the market, Vitravene, which was approved in 1998 to treat cytomegalovirus retinitis in AIDS patients. Isis' experience developing that product should help contribute to Pfizer's ophthalmology program. The agreement also provides Isis with the opportunity to work with an expert that can extend the technology beyond the primary therapeutic focus.

Isis refocused its resources in January as a way to advance its pipeline of second-generation antisense drug candidates. It laid off 165 employees, reducing its cash flow and freeing it from dependence on the equity market. The company said it had enough money to take it through 2007. (See BioWorld Today, Jan. 11, 2005.)

The agreement with Pfizer is part of its plan to broaden its antisense pipeline through partners.

"We are focusing more on the metabolic, cardiovascular and inflammatory diseases, as well as cancer," said Navjot Rai, Isis' senior manager of corporate communications. "So this was a perfect opportunity for us to do some work with a large pharma outside of our focus area."

The company's technology platform allows for the discovery of selective drugs to almost any gene target. Isis has 11 antisense products in development, and it is working to develop a system to genetically identify infectious organisms.

Isis has worked in the field of ophthalmic disease before, when it provided some early chemistry work for Eyetech Pharmaceuticals Inc., of New York. Eyetech gained U.S. approval of Macugen in December to treat wet age-related macular degeneration. The product is marketed by Pfizer.

Another up-and-coming therapy for the same indication is Lucentis, developed by South San Francisco-based Genentech Inc. Promising Phase III data were released Monday, showing that 95 percent of patients had improved or maintained vision compared with about 62 percent of those in a control group. Eyetech's shares fell more than 45 percent Tuesday as a result.

While drugs such as Macugen and Lucentis offer a marked benefit to patients, they by no means serve as a cure and there is room for additional therapies, Bennett said.

"Ultimately, what we'd like to do with Pfizer is identify additional therapeutic targets, not to compete, but really to augment the existing therapies," he said.

In other partnering news:

Vical Signs With AnGes For HGF Products

San Diego-based Vical licensed exclusive worldwide rights to its non-viral gene delivery technology to AnGes MG Inc., of Tokyo. AnGes will use the technology to develop and commercialize DNA-based products encoding hepatocyte growth factor (HGF) for cardiovascular applications.

Terms call for Vical to receive an initial up-front payment of $1 million, as well as potential milestone and royalty payments.

HGF is known to facilitate the growth of new blood vessels, and DNA-based delivery causes production of HGF at the site of injection. The resulting angiogenic effect should alleviate ischemic disease, in which narrowed or diseased blood vessels restrict blood flow. It might provide an alternative option when conventional drugs, balloon catheterization or surgery does not work.

Within the last two years, AnGes has initiated Phase II trials in the U.S. and Phase III trials in Japan with DNA-based HGF for peripheral arterial disease. It also started Phase I trials in the U.S. last year for ischemic heart disease. The company has partnered with Daiichi Pharmaceutical Co. Ltd., also of Tokyo, for worldwide development and commercialization of DNA-based HGF for both indications.

Vical's stock (NASDAQ:VICL) rose 12 cents on Tuesday, to close at $3.80.

Myriad Licenses IP For Salmedix's Cancer Program

Myriad Genetics Inc., of Salt Lake City, exclusively licensed its technology for using the single R-enantiomer of etodolac to Salmedix Inc., of San Diego.

Salmedix will use the technology to develop cancer therapeutics.

Myriad received a $2.5 million up-front payment and is entitled to developmental and commercialization milestone payments, as well as royalties on net sales.

Myriad's intellectual property, which is covered by several issued and pending patents in the U.S., Europe and Japan, will give Salmedix additional protection for its clinical candidate SDX-101 and other potential analogues. The product is R-etodolac, a single enantiomer of etodolac, that induces apoptosis in malignant lymphocytes and is devoid of anti-inflammatory activity. Salmedix started a Phase II trial in September in 80 patients with chronic lymphocytic leukemia, who are receiving a standard chemotherapy regimen alone or in combination with SDX-101 for multiple cycles.

Privately held Salmedix signed a definitive merger agreement earlier this month in which Frazer, Pa.-based Cephalon Inc. would acquire all of its outstanding capital stock for $160 million in cash, and up to $40 million in milestone payments. (See BioWorld Today, May 16, 2005.)

Myriad's stock (NASDAQ:MYGN) fell 2 cents on Tuesday, to close at $17.06.