Inside the rarefied world of polymer drug manufacturing

The world is a big place. Across its wide expanse are hundreds of facilities where a drug company can have a pharmaceutical active ingredient made to order.

If the active ingredient happens to be a polymer, though, that list of places quickly narrows down, perhaps to just one: an 80-year-old industrial park on the Danube River in Linz, Austria. Within the park is a factory that must be visited by any company seeking to develop a polymer as a drug.

Gerrit Klaerner and Wilhelm Stahl know that factory well. Between them, they have visited it many times as employees of companies that specialize in developing polymers to treat life-threatening illnesses. Today, as executives of Tricida, they are counting on the factory to help bring their latest, and possibly most important, polymer drug to market. Moreover, they want to get it there fast.

Polymer drugs constitute a tiny corner of the pharmaceutical world. Most drugs, be they small molecules or biologics, bind to or otherwise inhibit the action of proteins in the body. Polymer drugs are different. Rather than interact with the body, they stay unabsorbed, capturing unwanted salts or acids in their molecular webs until they are excreted away.

One example is Daiichi Sankyo’s Welchol, a polymer that binds bile acid, which the body makes from cholesterol. Eliminating bile acid prompts the body to make more, reducing cholesterol levels in the process. Another polymer drug is Sanofi Genzyme’sRenvela, which treats chronic kidney disease by sopping up potentially deadly excess phosphates.

Klaerner is a German polymer chemist who has spent most of his career developing polymer drugs. He moved to the U.S. in 1997 for a postdoc in California. When it ended, he got a job at Symyx Technologies, a high-throughput experimentation firm founded by the renowned chemists Peter G. Schultz and Alejandro Zaffaroni.

After about five years, Klaerner started a pharmaceutical spin-off of Symyx called Ilypsa, which set out to invent a competitor to Renagel, a predecessor of Renvela. Drawing on Symyx’s technology and experience in polymer synthesis, Klaerner and his small team developed a new polymer that could bind phosphates better than Renagel. Ilypsa licensed the drug to Astellas Pharma and was later acquired by Amgen for $420 million.

The following year, Klaerner helped launch Relypsa, an Ilypsa spin-off formed to come up with a potassium-binding polymer, also for people with kidney disease. Once again Klaerner was successful. Relypsa won U.S. Food & Drug Administration approval for the drug, called Veltassa, in 2015. The Swiss firm Vifor Pharma acquired Relypsa the following year for $1.5 billion.

Klaerner had already moved on by then. In 2013, eager to try his hand at polymer drugs yet again, he left Relypsa to launch Tricida. The name refers to his third effort as well as the substance the firm seeks to bind: hydrochloric acid, which builds up in people with kidney disease in a condition called metabolic acidosis.

Although Ilypsa and Relypsa were both successful, Klaerner sees Tricida as a culmination of his pursuit of polymer chemistry for kidney disease. The first two drugs treat symptoms of the disease. “Our goal is to have a nonabsorbing polymer that is disease modifying,” he says. “We want to treat both the complications and the underlying reasons for kidney disease.”

Nephrologists have long known that people with kidney disease experience acid buildup, which can accelerate the disease and cause muscle breakdown and bone loss. They typically treat it by administering a sodium or potassium base to neutralize the acid. But the same people often have conditions like hypertension, elevated potassium, and fluid overload that are exacerbated by such bases.

Klaerner knew a polymer could do the same job without introducing unwanted metals or ions; he also knew it wouldn’t be an easy polymer to design. “It was more challenging than potassium and phosphate,” he says. “We had to design a polymer that removed the right type and the right amount of acid from the body.”

Drawing on people he knew from earlier polymer design efforts, Klaerner brought together a dozen Ph.D. chemists and analytical experts in labs in Menlo Park, Calif.In previous efforts to design polymers that bind potassium and phosphates, the scientists had older polymer products like Renagel as guides. “This time there was no template,” Klaerner says.

Yet in September 2014, a year after he assembled the team, Tricida announced the discovery of a drug candidate, called TRC101. Although he won’t disclose the structure, Klaerner calls it a cross-linked amine polymer designed to selectively bind large quantities of protons and chloride ions without binding desirable fatty acids, bile acids, and other ions.