At the same time that Acuity Pharmaceuticals Inc. finished enrolling patients in a second Phase II trial for its lead RNAi-based drug in wet age-related macular degeneration and diabetic macular edema, the company licensed an early stage anti-inflammatory siRNA from ZaBeCor Pharmaceutical Co.

Acuity entered a license option agreement with ZaBeCor for exclusive development and commercialization rights to the small interfering RNA (siRNA) product in ocular settings, in exchange for an up-front payment, milestones and royalties. Specific terms were not disclosed, but the deal is "attractive for both parties," said Dale Pfost, Acuity's chairman, president and CEO, "based on milestones and a carrying interest in the success of the product."

It is the second addition to Acuity's growing ophthalmic pipeline in recent weeks. In mid-April, the Philadelphia-based firm in-licensed exclusive worldwide rights to N-chlorotaurine, a small-molecule anti-infective, from Pathogenics Inc., of Hingham, Mass.

Since its founding in 2002, Acuity has focused most of its resources on advancing its lead candidate, Cand5, into and through clinical development in age-related macular degeneration (AMD) and diabetic macular edema. But the company has become "very serious about building our portfolio over the last six to nine months," Pfost told BioWorld Today. "In particular, we've been looking at opportunities that leverage our expertise," and the program from ZaBeCor is a "good example of that."

The compound from Philadelphia-based ZabeCor is aimed at silencing the Syk kinase, a gene associated with inflammation and believed to be "a central player in the inflammation cascade," with potential applications in ophthalmic indications, Pfost said.

ZaBeCor is developing the product in pulmonary indications under the trade name Excellair and has conducted preclinical studies that have demonstrated the drug's potential to act against inflammation with the same benefits of steroids without the side effects.

"There's a very significant and impressive body of research and development as it relates to the application in asthma," said Samuel Reich, co-founder of Acuity and vice president of research and development. "The pharmacology is very impressive and profound, and we look forward to testing it in ocular settings," such as uveitis and ocular allergies, as well as potential activity against the inflammation that contributes to vision loss caused by macular degeneration.

"We believe it will have a broad role in ocular pharmaceuticals that can be developed for both" front-of-the-eye and back-of-the-eye diseases, Reich added.

The company has not released a specific timeline for the product's development; however, Pfost said Acuity plans to file at least two investigational new drug applications by the end of 2007, with two more to follow by the end of 2008. But, at this time, it's not clear yet which programs will be advancing first, as the company expects to sign "a few more licensing deals" in the coming months, he added.

"It's quite an exciting stage for the company because we've demonstrated success in the process of nurturing our lead candidate so far," Pfost said, "and that same capability is going to be turned to a stream of additional candidates," and the next two years to four years will see "a few select candidates marching through later-stage clinical development."

In the meantime, work continues on Cand5, a siRNA that targets vascular endothelial growth factor (VEGF). In February, the company completed enrollment in a Phase II study in wet AMD, with top-line results expected around mid-year, and last week Acuity announced enrollment completion in a Phase II trial in diabetic macular edema. Results from that trial should be available in the fourth quarter.

While other drugs on the market or in development for AMD - Melville, N.Y.-based OSI Pharmaceuticals Inc.'s Macugen and South San Francisco-based Genentech Inc.'s Lucentis - are designed to inhibit VEGF, Acuity's RNAi-based approach is designed to shut down the production of VEGF at the source. Early results suggested that Cand5 also would require less frequent dosing.

"We aspire to the position of having the maintenance drug of choice for patients," Pfost said. "Having four visits to physicians every year as opposed to 10 or 12 is certainly a very attractive prospect we think Cand5 can provide."

Acuity is not alone in its RNAi work in ocular indications, such as AMD. A potential competitor against Cand5 could be Sirna Therapeutics Inc.'s Sirna-027, a chemically modified siRNA that targets VEGF receptor 1. That product, anticipated to begin Phase II this year, is part of Sirna's potential $250 million partnership with Allergan Inc., of Irvine, Calif. (See BioWorld Today, Sept. 30, 2005.)

At this time, Acuity retains all rights to the product, though it likely will initiate "strategic discussions," once it has Phase II data in hand, Pfost said. Even then, the company might consider building its own sales force for the back-of-the eye disease market.

"We're not averse to actually becoming a full-fledged ophthalmology pharmaceutical company," Pfost said.