Read the full article from the Wisconsin State Journal here. 

When one door closes, another door opens … and it could be even better than the first.

At least, that’s the case for Arrowhead Pharmaceuticals, a Pasadena, California company with most of its employees in Madison.

A year and a half after Arrowhead suffered a devastating blow to its drug development program, the company has received $10 million from Amgen, one of the world’s biggest biotechnology companies, for advancing with one of two drug prospects Amgen has licensed from Arrowhead.

It is Amgen’s first milestone payment from a 2016 agreement that gave Arrowhead $56.5 million upfront and eventually could funnel $600 million more to the company. The payment marks the start of clinical trials on AMG 890, Amgen’s drug — from Arrowhead technology — aimed at lowering levels of a liver protein tied to cardiovascular disease.

“We are thrilled that Amgen has advanced AMG 890 into a phase 1 clinical study,” Arrowhead president and CEO Chris Anzalone said. “Amgen has extensive expertise in developing and commercializing innovative cardiovascular medicines.”

It is Arrowhead’s third product in human clinical tests based on the company’s RNA interference (RNAi) technology, used to reduce production of proteins tied to specific diseases.

“We view our collaboration as further validation of the potential for Arrowhead’s proprietary targeted RNAi molecule, or TRiM, technology platform,” Chris Anzalone said.

Separate from the Amgen agreement, Arrowhead’s ARO-HBV, aimed at chronic hepatitis B, and ARO-AAT, to treat liver disease tied to alpha-1 antitrypsin deficiency, already are in clinical trials.

Early data from a safety test of ARO-AAT showed one low dose reduced levels of a mutant version of alpha-1 antitrypsin by an average of 87 percent, and remained high for eight weeks with no severe side effects.

The disease affects about 250,000 patients in the U.S. and Europe, said research analyst Y. Katherine Xu of the William Blair investment firm. Xu called the results “encouraging” in a July 23 research note and said the drug “is positioned to become the company’s first potentially approved therapy.”

Arrowhead just started testing ARO-HBV on patients in May, but Xu said animal study results were “tantalizing, showing strong trends toward clinical cures.”

Arrowhead plans to seek federal regulatory approval to start clinical trials on three more products before the end of the year. Two are cardiometabolic — referring to cardiovascular disease and diabetes — and one targets cystic fibrosis, said Vincent Anzalone, vice president of finance and investor relations. A prospective drug against kidney cancer is on the agenda for 2019 and there is “a handful of others beyond that,” he said, all built on the targeted RNAi molecule platform.

Company comeback

The developments are particularly sweet for Arrowhead because in November 2016, the U.S. Food and Drug Administration abruptly halted early patient tests of similar drugs after an undisclosed number of animals died in animal tests. The drug was administered differently and in much higher doses than in humans. In human tests, only three patients suffered “serious adverse events,” two of which were fevers, successfully treated with acetaminophen.

Shares of the publicly traded company’s stock plunged 60 percent overnight to $1.76, and 30 percent of its staff was cut.

So Arrowhead revamped the way its RNAi drugs travel to their target. “It’s a much simpler molecule” that should be easier to manufacture and improve safety margins, Vincent Anzalone said.

The new formulation is administered by a shot under the skin, rather than intravenously under the previous format. That will be more convenient for patients, as well, he said.

“We have come back full circle,” he said.

Arrowhead has about 110 employees — 20 in California and 90 in Madison, and Madison will “absolutely” stay open, Vincent Anzalone said. The company, at 502 S. Rosa Road, had been part of Mirus Bio Corp., founded in 1995 from UW-Madison research, sold to Roche in 2008 for $125 million and acquired by Arrowhead in 2011.

Arrowhead’s stock closed Wednesday at $15.14 a share, up nearly 4 percent from the day before. The stock had hit $17.50 last week, its highest level in four years, “due in part to faster-than-expected clinical progress,” analyst Xu wrote.