BioWorld Today Contributing Writer

Using technology acquired from Pfizer Inc., San Diego-based biotech MingSight Pharmaceuticals Inc. has its eye on an oral therapy for retinal diseases.

MS-553, the lead compound licensed under the exclusive worldwide agreement, has demonstrated efficacy in preclinical models of diabetic retinopathy (DR). A second compound also has demonstrated supportive properties in both in vitro and in vivo studies.

Eventually, the company hopes to develop therapies to treat not only DR but also diabetic macular edema (DME), uveitis and dry eye.

Michael Niesman, MingSight's chief scientific officer, left academic ophthalmology research in 1998 to join the LaJolla, Calif.-based biotech start-up Agouron Pharmaceuticals Inc., which was acquired by Warner-Lambert Co. in 1999 before that firm was subsequently swallowed up by Pfizer. (See BioWorld Today, Nov. 5, 1999.)

Niesman headed Pfizer's ophthalmology research until 2009, when the program was among a slew of indications axed by the company as it reshuffled its priorities. (See BioWorld Today, Oct. 1, 2008.)

Niesman and colleagues pursued several opportunities to spin out the ophthalmology assets while they were still inside Pfizer, but their efforts were hampered by the global financial crisis. Serendipitously, a venture capitalist introduced Niesman to Kai Zhang, a physician with experience in the pharmaceutical industry who had moved to San Diego and was interested in starting a company. The two began to talk, and by the end of 2009, they had formed MingSight – a name that incorporates the Chinese word for "bright."

MS-553 is the product of the Pfizer's most advanced ophthalmology program, according to Niesman. Targeting DR, the compound involves components to treat both the leakage produced by high glucose levels in the blood as well as the inflammatory cascade that occurs when the condition becomes chronic, leading to diabetic macular edema (DME). In a diabetic mouse model, MS-553 reduced retinal leakage by 100 percent after just three days of treatment. A precedent compound obliterated 95 percent of the retinal leakage induced by vascular endothelial growth factor (VEGF) – one of the key drivers of diabetic eye disease.

Importantly, those results were produced after diabetes was well established, working "in an intervention mode, not a prevention mode," Niesman told BioWorld Today.

In addition, MS-553 has anti-inflammatory properties, down-regulating the expression of Intercellular Adhesion Molecule-1, or ICAM-1, and reducing retina leukostasis by 80 percent to 90 percent. The precedent compound also has demonstrated normalized retinal flow in diabetic animals and humans.

Oral administration – the compound would be taken once daily – provides for better ocular efficacy and lower ocular toxicity than invasive treatments such as Lucentis (ranibizumab, Roche AG and Novartis AG) and off-label Avastin (bevacizumab, Roche), Niesman said. Although clinical trials of those drugs have suggested promising prospects for treating DR and DME, "the best results require an injection about once a month, and for a young diabetic patient with diabetic macular edema, that's a daunting proposition," he observed.

Even in pill form, MS-553 crosses the blood-retina barrier to achieve high concentrations in the retina.

"Our hypothesis is that we can achieve that kind of efficacy with an oral treatment, with better compliance and no side effects from the intraocular injection," Niesman said.

As part of the licensing agreement, signed in October 2010, MingSight agreed to pay Pfizer an undisclosed up-front fee and a convertible note as well as development and sales-related milestones and royalties on future sales. The company also established a joint venture with an undisclosed pharmaceutical manufacturer in China, which is providing financial support to move the compound through chemical manufacturing and control and toxicity studies and gear up for production there.

MingSight retains the rights to MS-553 outside China and, long term, hopes to attract a global development partner.

Though officials declined to specify how much the company has raised to date, the amount is sufficient to advance the compound to commercialization in China, according to Zhang, the company's CEO and only other full-time employee. MingSight expects the funding to allow the Chinese trials to be conducted to U.S. standards through Phase II.

The compound was nearly ready to enter safety studies when Pfizer halted the ophthalmology program, "so we're picking it up from there," Niesman said. "We're about 14 months away from first in humans."

Competitors continue to emerge in the diabetic eye disease space. In addition to Lucentis and Avastin, last month Molecular Partners AG, of Schlieren, Switzerland, secured a potential $420 million deal with Irvine, Calif.-based Allergan Inc. for its lead molecule, the VEGF antagonist MP0112, in ophthalmic indications. (See BioWorld Today, May 5, 2011.)

At the Association for Research in Vision and Ophthalmology meeting in Fort Lauderdale, Fla., Molecular Partners reported positive data from two Phase I/IIa trials in patients with wet age-related macular degeneration or DME.

But the fact that MS-553 had a track record at Pfizer – and is administered orally – differentiates MingSight in the market, Niesman said.

"This was licensed out from a big pharma, so it has a very strong background," he explained. "The compound itself was formulated in a structure-based drug design program, so it's quite potent and selective. Plus, when we give this compound orally, we get good exposure levels in the eye without having to give a large dose. We'll have a combination of safety and efficacy without having to resort to invasive administration."