Arrowhead turns to TRiM tech to drive clinical pipeline and collaboration

By Dan Stanton

- Last updated on GMT


Related tags Pharmacology Clinical trial

Arrowhead Pharmaceuticals says it is looking to move six candidates into the clinic within the next year thanks to its newly unveiled RNAi delivery platform.

After the US Food and Drug Administration (FDA) halted a Phase II trial for its Hepatitis B candidate Arc-520 in November 2016​, Arrowhead Pharmaceuticals axed around 30% of its workforce and several pipeline products based on its Ex1 synthetic dynamic polyconjugate (DPC) drug delivery platform.

Effectively, Arrowhead “moved from a clinical stage company with two Phase II candidates and one Phase I candidate to a preclinical stage company overnight,”​ CEO Christopher Anzalone told investors during a financial call Tuesday.

But just over a year on, the firm is now banking on its new targeted RNA interference (RNAi) molecule technology platform “to go from zero clinical programs to five, or possibly six, over the next 12 months,”​ he said.

Unveiled in September, the Targeted RNAi Molecule (TRiM) platform uses ligand-mediated delivery and to enable tissue-specific targeting. It comprises of a potent RNA trigger with high affinity targeting ligands, linkers and pharmacokinetic enhancing tech optimised for each drug candidate.

According to Anzalone, the platform offers several advantages over other RNAi technologies, including: “1) Simplified manufacturing and therefore reduced costs, 2) multiple routes of administration including subcutaneous injection and inhaled administration, and 3) potential for improved safety, because smaller molecules with reduced metabolites may reduce the risk of intracellular accumulation.”

He added TRiM does not rely on DPCs like the Ex1 platform, “so we expect substantially wider safety margins than we had in previous generations.”


In September 2016, Arrowhead licensed a subcutaneous cardiovascular RNAi therapy candidate to Big Biopharma firm Amgen in a deal worth up to $617m. The candidate, known as AMG-890, is expected to enter the clinic in 2018.

AMG-890 is built on the TRiM platform and Arrowhead is looking to replicate such collaborations across a number of therapy areas.

“It makes sense to do more collaborations like we did with Amgen last year for some of our programmes,”​ Anzalone said.

“The world has seen how fast we were able to move over the past 12 months, and that the TRiM technology may be optimised to address a variety of target tissues, so we believe we are well positioned to attract high quality partners to maximize the number of products we can ultimately get to patients.”

For the full year ending September 30 2017, Arrowhead reported revenues of $31.4m compared to $158,000 in FY 2016, due to the upfront payments from Amgen. The firm reported a net loss of $34.4m, down from $81.7m year-on-year.

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