Most drugs act by interfering with signaling proteins in cells or receptors on cell surfaces. San Diego-based Zacharon Pharmaceuticals has a different idea, by trying to interrupt the complex carbohydrates known as glycans, that can alter the function of proteins.
This concept has been around the biotech industry a number of years, without a whole lot to brag about. But Zacharon was able to raise $3.5 million in venture capital for the idea a few weeks ago, while also getting a $2.2 million research grant from the National Institutes of Health. So I stopped by to hear more about it a few weeks ago from Charles Glass, the co-founder and senior vice president of research.
Zacharon thinks it has overcome some of the challenges that tripped up companies like San Diego-based Cytel and Alameda, CA-based Glycomed in the 1990s, Glass says. Instead of directly trying to target these complex structures, Zacharon has found a way to inhibit them by blocking easier-to-hit enzyme targets that make the glycans in the first place. It plans to do it through conventional small-molecule pills, discovered through highly-efficient screening methods, Glass says. These methods are common in the pharmaceutical industry, but no one has yet applied them systematically to blocking glycan targets, he says.
“There are a whole class of targets that are being ignored,” Glass says. “We think the time is right for glycans.”
Zacharon got its start in 2004, founded by Glass, a former scientist at Johnson & Johnson Pharmaceutical Research Insitute in La Jolla, CA, and Jeff Esko, a researcher at the University of California, San Diego. The company now has eight employees, led by CEO Jay Lichter, who joined last month in connection with the venture financing from San Diego-based Avalon Ventures.
The company’s first drug candidate is for mucopolysaccaridosis (MPS), a rare genetic disease in which faulty or missing enzymes cause a buildup of complex carbohydrates (glycans) in children’s bodies, leading to nerve damage, physical deformities, and slowdowns in mental development. Shire’s idursulfase (Elaprase) and another drug, BioMarin Pharmaceuticals and Genzyme’s laronidase (Aldurazyme), are enzyme-replacement therapies that are FDA approved for forms of MPS. One weakness of these large-molecule drugs is that they can’t cross the blood-brain barrier, which means complex carbohydrates still build up in the brain, harming mental development and causing behavior problems.
A small-molecule drug from Zacharon could be taken orally, and have a good chance of crossing the blood-brain barrier and mitigating those cognitive effects, Glass says.
Lots of work still needs to be done to prove this hypothesis is true in humans. The work hasn’t yet advanced into its first clinical trial. The trials should be pretty straightforward, though, because researchers will be able to see whether glycans are being blocked by the drugs and tell early on if they are working or not, Glass says.
Before heading out the door, I had to ask about the name. Glass rolled his eyes a tiny bit, since he’s heard this one before, from people who ask if it was inspired by guys named Zach and Ron.
The actual name has meaning connected to the goal of the company. It comes from the Greek root word saccharo, which means sugar. Those sugars can make glycans. If Zacharon figures out how to block these glycan targets that other pharmaceutical companies haven’t, it could be a pretty sweet little company.
