Arrowhead Pharmaceuticals is turning its financial tie to a promising but still experimental heart drug into $250 million in immediate cash, a move that comes days after the reporting of Phase 2 data showing the therapy successfully reduced levels of a protein associated with the risk of cardiovascular disease.

The data for the drug, olpasiran, were reported by Amgen, which licensed the RNA therapy from Arrowhead. That deal grants Pasadena, California-based Arrowhead royalties from Amgen’s sales of the drug, if it reaches the market. That market is a big one as heart disease remains a leading cause of death, positioning oplasiran as a potential blockbuster seller.

Arrowhead is tapping into olpasiran’s promise by selling the drug’s royalty rights to Royalty Pharma, a company that strikes deals to acquire royalties for development-stage and commercialized drug assets. According to financial terms announced Wednesday, the $250 million coming to Arrowhead is an upfront payment. Royalty Pharma could pay the biotech up to $160 million more contingent on the drug’s achievement of clinical, regulatory, and sales milestones.

Olpasiran is an RNA therapy that works by RNA interference (RNAi), an approach that is sometimes referred to as called gene silencing. The small interfering RNA in the drug stop a gene from producing a disease-causing protein. Olpasiran is designed to reduce levels of lipoprotein (a), a type of the “bad” form of cholesterol that increases the risk of cardiovascular problems, such as heart attack and stroke. The drug comes from Arrowhead’s technology platform called Targeted RNAi Molecule, or TRiM.

Amgen licensed the rights to olpasiran and a second RNAi drug in 2016, committing $56.5 million plus another $617 million tied to the achievement of milestones. The deal granted Arrowhead up to low double digit royalties from olpasiran sales. Amgen took over responsibility for clinical development of the drugs.

On Sunday, Amgen presented Phase 2 results for olpasiran during the American Heart Association Scientific Sessions conference in Chicago. The double-blind, placebo-controlled study enrolled 281 adults with high lipoprotein (a) levels and a history of atherosclerotic cardiovascular disease. Four doses of the subcutaneously injected drug were tested in this dose-finding study.

Amgen reported that more than 98% of participants who received the 75 mg dose (a middle dose) or higher achieved reductions in lipoprotein (a) of 95% or more compared to a placebo at week 36. The Thousand Oaks, California-based pharmaceutical company said adverse events were similar across both arms of the study, the most common one being injection site reactions. The data were also published Sunday in the New England Journal of Medicine. Based on the encouraging Phase 2 results, Amgen plans to proceed to a Phase 3 cardiovascular outcomes study expected to begin enrolling patients in December, the company said in an investor presentation on Monday.

Even though Arrowhead has signed away its rights to olpasiran royalties, it could still make money from Amgen’s progress with the drug. Arrowhead remains eligible for up to $400 million in milestone payments from its original deal with Amgen—rights not included in the Royalty Pharma deal.

“Olpasiran, which we developed and licensed to Amgen for further clinical development and commercialization, has the potential to benefit millions of patients worldwide by reducing the risk of cardiovascular disease,” Arrowhead President and CEO Chris Anzalone said in a prepared statement. “The early monetization of this potential royalty stream validates olpasiran’s significant potential and enables us to continue to invest in our TRiM platform and our diverse and growing pipeline of RNAi therapeutic candidates.”

The most advanced Arrowhead program is another cardiovascular drug candidate. ARO-APOC3 is designed to reduce levels of apolipoprotein C-III to treat hypertriglyceridemia, a disorder characterized by high blood levels of fats called triglycerides. The internal pipeline includes programs for diseases of the liver, lung, and muscles.

Beyond its Amgen partnership, Arrowhead has placed assets with other pharma companies. A 2018 deal gave Johnson & Johnson rights to an Arrowhead RNAi drug for chronic hepatitis B infection. In 2020, Arrowhead licensed to Takeda Pharmaceutical rights to an RNAi drug for a rare liver disorder. Last year, Horizon Therapeutics acquired rights to Arrowhead’s experimental gout treatment.

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