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Delivery development: Adherex and Scynexis work to perfect oral cadherin antagonist
May 2005
by Jeffrey Bouley  | 

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RESEARCH TRIANGLE PARK, N.C.—Although biopharmaceutical firm Adherex already has a promising N-cadherin antagonist currently in clinical trials, that drug candidate lacks a very important aspect: the ability to be administered orally. So, the company recently signed an agreement with drug discovery and development company Scynexis to find small-molecule candidates with similar activity.
 
"ADH-1, which is our first lead in the area of N-cadherin antagonists, has some very promising oncological opportunities, because if you antagonize N-cadherin on tumor cells, you can lead to tumor cell death. But you can also express it on tumor vessels to deplete the flow of nutrients into the tumor," explains Dr. Robin Norris, the president and COO of Adherex. "So, we have a very nice dual effect with this drug, and it is a cyclical peptide that is administered intravenously and is very well tolerated."
In fact, ADH-1 is progressing well through its development and is entering Phase II clinical trials, according to Dr. Brian Huber, Adherex's chief scientific officer.
 
However, Adherex sees other potential uses for such a drug, including chronic therapy to reduce the risk of metastasis, in which oral drugs may work better for patients than IV administration. Also, promising opportunities exist for N-cadherin antagonist drugs for non-oncological uses,  Norris notes, such as treatments for diabetic retinopathy and atheroma.
 
"We've done work on this already, and we have identified some good small-molecule candidates that could target very selective cadherins and lead to some good oral drugs," Norris says. "But while we have a lot of expertise, we're staffed in the mid-20s and our own chemistry capability is limited. We don't have the people or money to do everything, so we had to look at where our skills were best applied.
 
"Scynexis is expert at looking at structure design relationships for small molecules so that you can test for requisite properties, and they will be a great help in fine-tuning our own work. As we provide the biology, they provide the chemistry."
 
Scynexis has the ability to not only produce drugs a few milligrams at a time but offer a full-service capability up to early clinical supplies a least—in addition to producing the drugs at GLP standards for preclinical studies and GMP standards for clinical studies, he adds.
 
"Our expertise is to quickly identify the promising compounds and move them into candidate selection and clinical testing on a highly confidential basis," says Yves Ribeill, the president and chief executive officer of Scynexis. "We've had several triumphs in biotech and pharma already, we have excellent small-molecule understanding from early chemistry to GNP candidate selection, and we offer—in a certain sense—a one-stop shop for Adherex."
 
Good chemistry isn't enough to form a foundation for a lasting collaboration, though, which is something both companies are aiming for.
 
"The communications side of these collaborative projects we engage in is one of the most important features," stresses Mike Peel, director of medicinal chemistry for Scynexis. "We take a lot of time and effort to make sure that's in place so that there is good communication flow between Adherex scientists and Scynexis chemists. That's facilitated by our software packages that allow viewing of data simultaneously and regular face-to-face meetings. The goal is to be equal partners in the work, and our location doesn't hurt, since our companies are neighbors."
 
"Implicit in that is that we will have a dedicated project team here," adds Russ Outcalt, Scynexis' executive director of operations. "Adherex will get to know our scientists on this project well—and the same goes for us getting to know their project team—and that is critical for building the relationship and moving this effort forward."
 
Code: E050517

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