Rewriting Life

Multifunctional Drugs May Offer Better-Than-Additive Effects

A startup called Catabasis is developing drugs that hit diseases at multiple targets.

Most drugs are designed to target a disease in just one way.

Sometimes a whole is greater than the sum of its parts. The startup Catabasis Pharmaceuticals is hoping that will hold true for the multifunctional drugs it’s developing.

The company, which is based in Cambridge, Massachusetts, has developed a chemical linker technology that can bring together two different therapeutic components so they have a greater effect on their target pathways than they would if both compounds were administered separately. The company hopes their lead therapy will target the complex inflammation pathways in patients with irritable bowel syndromes such as Crohn’s disease and ulcerative colitis.

In a preliminary test of 105 patients, the potential drug, taken as a pill, safely decreased the activity of a key molecule in an inflammation pathway that plays an important role in such disorders. That effect was not seen when the two components were given to subjects simultaneously but without being linked.

“When you suppress pro-inflammatory and activate anti-inflammatory responses, you produced an effect which is typically two to three times more potent than hitting either one of those nodes individually,” says Mike Jirousek, cofounder and chief scientific officer of Catabasis.

“Many complex diseases are driven by multiple proteins or gene products working together,” says Ravi Iyengar, director of the Experimental Therapeutics Institute at the Icahn School of Medicine at Mount Sinai in New York. “It’s very hard to tweak it at one point and get an effect. In theory, it’s much easier if you tweak it at multiple points to reset the balance. The ideal would be one drug that hits multiple nodes, but maybe that’s a bit of dreaming.”

Catabasis has found a way around the challenge of identifying a single active molecule that can hit multiple pathways effectively: using a chemical linker to bring together two active molecules. The synergistic effect of the linked molecules may arise from the fact that the two compounds both “get to the right place at the right time,” says Jirousek.

The linker that brings the two components together also inactivates them until they get to the right cell and helps deliver them to the correct tissues. The company achieves these effects by taking advantage of naturally occurring enzymes that can cut up the linker, freeing the two active components. Different linkers have also been developed to carry molecular keys for cell types in different body systems, including the blood, the liver, and even the brain, says Jirousek. 

In addition to the drug for irritable bowel syndrome, the company is developing other therapeutics, some of which aim at high triglyceride levels, psoriasis, and multiple sclerosis. All bring together compounds that are proven to be safe. “We wanted to take as much risk off the table as we could, so we started with safe molecules that already have some known level of activity,” says Jill Milne, cofounder and CEO.

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