Acuity Pharmaceuticals Inc. and Intradigm Corp. agreed to combine their work in the field of RNA interference to develop topical and other formulations of Acuity's Cand5, a compound aimed at treating wet age-related macular degeneration.

Philadelphia-based Acuity also exclusively licensed the use of Intradigm's ophthalmic drug discovery and delivery platforms and obtained rights to its ophthalmic target discovery engine. Financial terms of the deal were not disclosed, though it will include up-front payments, and possible milestone and royalty payments to Intradigm.

The collaboration will begin with Intradigm taking over the initial activities and "transitioning to Acuity over the next 12 months or so, as we approach the clinic," said Acuity President and CEO Dale Pfost, who described the collaboration as the "alignment of two well-established firms in the RNAi field."

While Intradigm has a broad-based RNAi platform, the Rockville, Md.-based company said its plan was to leverage its ophthalmic discovery and delivery technology while narrowing its focus to cancer therapeutics. The firm's lead product candidate, ICS-283, is an siRNA compound in late preclinical development for solid tumors.

Intradigm is "entrusting to Acuity the active and aggressive pursuit in ophthalmology," Pfost said. "And this collaboration marks the initiation of our topical program, which we think is a very promising route of administration" for Cand5.

The partnership also allows for the development of other potential formulations, such as systemic or sustained-release versions of Cand5, which now is administered in an intravitreal injection. Simpler administrations could be used in the development of preventative treatment options for patients who might be susceptible to certain eye diseases.

As the first RNAi product to be cleared for human trials, Cand5, a small-interfering RNA therapeutic, is expected to complete Phase I development in the next several weeks and begin Phase II studies later this year.

Like other products that have recently garnered attention in the wet AMD space, Cand5 is an inhibitor of VEGF (vascular endothelial growth factor), which has been shown to be the primary cause of the development of ocular neovascularization and vision loss associated with AMD. The first VEFG inhibitor to achieve approval for wet AMD, Macugen, was launched in January by New York-based firms Eyetech Inc. and Pfizer Inc., and South San Francisco-based Genentech Inc. recently released positive Phase III data for its VEGF inhibitor, Lucentis.

Those products both were in development when Acuity began working on its RNAi-based therapy, said Sam Reich, vice president of research and development and co-founder of Acuity, who developed Cand5.

"VEGF inhibitors were becoming the most exciting thing in treating wet AMD," he told BioWorld Today, "but we realized that [Macugen and Lucentis] had multiple limitations, specifically in frequency, potency and safety."

Reich said Cand5 was designed to use the cell's natural RNAi machinery to inhibit VEGF, a mechanism of action that Acuity believes will be superior to an aptamer or antibody therapeutic in efficacy and safety, as well as a potential for less-frequent dosing.

"The pharmacologic mechanism lends itself, scientifically, to aspiring for longer intervals between dosing," he said, though specific dosing levels and frequency will need to be determined during the upcoming Phase II studies.

"I think the physician community is excited by having the target validated by Genentech and Eyetech," Reich added, "and then having a company like Acuity come along with a molecule that could more adequately address the target."

Other companies working on RNAi therapeutics to treat wet AMD include Boulder, Colo.-based Sirna Therapeutics Inc., which began Phase I trials in November with Sirna-027, an siRNA therapeutic targeting VEGF, and Alnylam Pharmaceuticals Inc., of Cambridge, Mass., which expects to enter the clinic in the second half of 2005 with its RNAi therapy, also a VEGF inhibitor.

Acuity, which was founded in 2002 to address ophthalmic diseases, also plans to conduct Phase II studies of Cand5 in diabetic retinopathy, a complication of long-term diabetes that causes leaking of the retinal blood vessels and can result in blindness.

The company has raised more than $20 million, including a $15 million Series B round completed in October that coincided with the start of the Phase I Cand5 study. (See BioWorld Today, Oct. 8, 2004.)