On the cusp of its first clinical trials and its largest round of private financing, Acuity Pharmaceuticals Inc. has a clear vision of its future.
The ophthalmic drug development company has its sights set on applications of RNA interference to treat diseases of the eye - age-related macular degeneration (AMD) and diabetic retinopathy. To that end, the Philadelphia-based firm is bullish about the prospects of its lead product, Cand5, as are the investors who have committed $10 million to Acuity through a Series B round of financing that could grow to $15 million.
"We are well progressed in all the preparations for filing our [investigational new drug application] in just a few months, so we have concluded a large fraction of the formal preclinical work," Acuity President and CEO Dale Pfost told BioWorld Today. "We expect to file our IND later this year and be in patients by the end of the year."
He noted that instead of initially testing the drug in healthy volunteers, Phase I studies would evaluate it in AMD patients. Future Phase II work will be powered for efficacy. The small interfering RNA product is designed to shut down vascular endothelial growth factor (VEGF), which stimulates blood vessel overgrowth and regulates blood vessel permeability.
"VEGF is central to two aspects of AMD - the leakage at the back of the eye and the creation of neovascularization," Pfost said, noting that difficulties have arisen in delivering enough of a drug for optimal effect. "While that antagonist approach is showing promise and certainly is validating the target, you'd really like to stop the VEGF cold, before it's produced. The only way to really do that is to use RNA interference."
Published preclinical data printed three months ago in Retina showed that Cand5 significantly inhibited both the blood vessel overgrowth and vascular leakage that lead to vision loss in AMD in a primate disease model. The findings also demonstrated that a single dose reduced both neovascularization and vessel leakage in a dose-dependent manner for more than five weeks.
Pfost said Cand5 is delivered via injection to the eye, where it moves toward the back and into retinal pigment epithelial (RPE) cells, which are responsible for producing VEGF.
"We've demonstrated already that our siRNA stops VEGF in the RPE cells before it's produced," he added. "So what we have is an effect that lasts for several weeks - it's highly potent - and therefore we think that the amount of VEGF that will be present between administrations is going to be vastly lower than using an antagonist."
Pfost said such evidence of efficacy and longer-lasting effects will set Cand5 apart from other products already on or near the market.
The current standard treatment for AMD and diabetic retinopathy, Visudyne (verteporfin), is marketed by QLT Inc., of Vancouver, British Columbia, and Novartis AG, of Basel, Switzerland. A late-stage product for the same diseases, Macugen (pegaptanib sodium), is being developed by partners Eyetech Pharmaceuticals Inc. and Pfizer Inc., both of New York.
"The diseases of the back of the eye have really been underserved, most notably AMD and diabetic retinopathy," Pfost said. "We think we will make a major step forward, compared to the current standard of care, and even the emerging standard of care."
Acuity also will use Cand5 to treat diabetic retinopathy, another ocular disease to which VEGF is central. Pfost said that program is about 12 months to 18 months behind the AMD program.
The technology underlying the company's approach stems from research at the Scheie Eye Institute of the University of Pennsylvania. Acuity's founders, Michael Tolentino and Samuel Reich, merged their respective research into a singular approach and created the company in October 2002. A retinal surgeon, Tolentino had worked in the VEGF field, while Reich was operating with siRNA.
"What's notable is that they very rapidly moved into validating proof-of-principle studies of siRNA approaches to anti-VEGF," Pfost said. "This was not just in vitro, but also very rapidly into disease models. So as it relates to RNA interference as a therapeutic, Acuity really stands first in the process. And as it relates to ophthalmic and anti-angiogenesis applications, we were the first in mouse disease models and first in the primate model."
Acuity, which has exclusive licenses to intellectual property developed at Scheie, has raised about $3.7 million to date. Its initial investors include family and friends, as well as two local seed capital firms, BioAdvance and Ben Franklin Technology Partners. Both are based in Philadelphia.
Pfost said Acuity's second round of financing has generated commitments of $10 million to date, and he expects that number to grow to $15 million before the round closes in a couple of weeks. Such funding would carry the 10-employee company's lead development program through Phase II.
Much of its current work is outsourced to a contract research organization, including efforts related to manufacturing, regulatory affairs and assay development. Further down the road, Pfost said Acuity could find itself in a position to partner Cand5 at the conclusion of Phase II work, though he added that the company also could opt to maintain its product rights and directly task it to retinal surgeons.
"We actually have a patent filing that's based on a drug, not just a platform technology," Pfost said. "Despite the fact that there may be visibility and limelight in a variety of directions in the field of RNA interference, I think the field is emerging around targets, indications and intellectual property rights that describe a drug. That's what the founders of Acuity were focusing on."