Arrowhead Pharmaceuticals (NASDAQ:ARWR) used its presentation at the JPMorgan Healthcare Conference to highlight a newly launched RNA interference (RNAi) therapy, a broad clinical-stage pipeline, and what management described as ample capital to advance multiple wholly owned programs.
Financial position and platform overview
President and CEO Chris Anzalone opened with a snapshot of the company’s financial profile, citing a stock price of $6.456 as of the prior Friday, roughly 136 million shares outstanding, and a market capitalization “around $9 billion.” Arrowhead reported about $920 million of cash and investments in its last filing, and Anzalone added several items not yet reflected in filings: $200 million from Sarepta that had been invoiced but not yet received, $200 million from Novartis that had been received but not yet reflected, and $930 million in recent offerings.
Rudemplo launch and triglyceride franchise expansion plans
Arrowhead’s first commercial product, Rudemplo (formerly plozasiran), was described as approved in the U.S., Canada, and China to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). Anzalone said the company launched the drug toward the end of November 2025 and characterized it as the first and only FDA-approved RNAi-based medicine for triglyceride reduction in adult FCS, as well as the first FDA-approved medicine using Arrowhead’s TRiM platform.
In phase 3 studies, Anzalone said Rudemplo produced about an 80% reduction in triglycerides from baseline in genetically confirmed and clinically defined FCS patients, with “something like 75%” of patients below 880 mg/dL and “something like 50%” below 500 mg/dL—thresholds he described as associated with pancreatitis risk. He also said the phase 3 program showed a reduced incidence of pancreatitis. Rudemplo is dosed once every three months via at-home subcutaneous administration, and Anzalone said the label includes no contraindications, warnings, or precautions.
Arrowhead outlined plans to expand Rudemplo’s label into severe hypertriglyceridemia (SHTG). Anzalone estimated about 6,500 FCS patients in the U.S. and a broader SHTG population of roughly 3 million people with triglycerides above 500 mg/dL, including about 1 million above 880 mg/dL. The company expects phase 3 SHTG studies to read out in the third quarter of 2026, followed by an sNDA filing in the fourth quarter of 2026, with a potential launch into the broader population in 2027.
On pricing, Anzalone said Arrowhead chose a “consistent one Rudemplo price model” and set pricing at $60,000, which he said would apply to FCS and the expected SHTG price. He said the company avoided pricing “at many hundreds of thousands of dollars” in FCS because it views SHTG as the larger opportunity and wanted payers to understand the value proposition, including the economic burden of pancreatitis. He noted the company’s estimate that a single bout of pancreatitis can cost “upwards of $60,000,” with 93% involving inpatient stays averaging 10 days.
Zodasiran for HoFH and ARO-Dimer-PA for mixed hyperlipidemia
Arrowhead also highlighted zodasiran, an ANGPTL3 silencing agent it is developing for homozygous familial hypercholesterolemia (HoFH). Anzalone estimated there are “only one to 2,000” HoFH patients in the U.S. In a phase 2 study, he said zodasiran reduced LDL-C by about 41% in HoFH patients, and by about 62% in patients on background PCSK9 inhibitors. A phase 3 HoFH study is enrolling, and management expects full enrollment in the first half of 2026. Anzalone said the intended commercial formulation would be quarterly, subcutaneous at-home dosing, which he contrasted with monthly intravenous infusions for ANGPTL3 monoclonal antibody treatments. He added that the program could leverage the existing Rudemplo commercial team and the same physician call points.
In mixed hyperlipidemia, Arrowhead is advancing ARO-Dimer-PA, a single “dimer” molecule designed to reduce both PCSK9 and ApoC3 expression. Anzalone described it as the company’s first dimer and “the world’s first dimer” to silence two genes in one molecule. He said nonclinical data in dyslipidemic monkeys showed reductions in non-HDL cholesterol, LDL cholesterol, and triglycerides, and that Arrowhead has generally seen good translation from nonclinical to clinical results.
The company is targeting what it estimates to be about 20 million U.S. patients with both elevated LDL cholesterol and elevated triglycerides. Arrowhead expects to begin dosing mixed hyperlipidemia patients in a phase 1/2 study “this month” and anticipates initial clinical data toward the end of the third quarter. Anzalone said that timeframe should provide a relatively fast read on whether the program can deliver meaningful LDL and triglyceride reductions with acceptable tolerability, and he also pointed to a potential regulatory pathway that could allow approval based solely on LDL reduction in a “fairly small” study.
Early obesity data and decision to remain unpartnered
Arrowhead presented early clinical observations for two obesity candidates, ARO-INHBE and ARO-ALK7, both aimed at disrupting the Activin E/ALK7 pathway to increase lipolysis and reduce fat storage. Anzalone emphasized that the data were an “early snapshot,” with studies still ongoing, but said the results were “interesting.”
- ARO-INHBE: Dose-dependent reductions in circulating Activin E, including a mean maximum reduction of 85% after a single 400 mg dose and a maximum observed reduction of 94%. Anzalone reported monotherapy visceral fat reductions of 9.9% at week 16 and 15.6% at week 24 after a single dose. In combination with tirzepatide in obese diabetic patients, he said weight loss at week 16 was 9.4% versus 4.8% with tirzepatide alone, along with about 23% visceral fat loss, 15% total fat loss, and a 76.7% liver fat reduction.
- ARO-ALK7: Anzalone said it is the first RNAi therapeutic he is aware of to demonstrate knockdown of an adipocyte-expressed target in humans, citing a mean 88% reduction in ALK7 mRNA expression and a maximum of 94%. He said monotherapy produced a 14% placebo-adjusted reduction in visceral fat at week eight after a single dose.
Next steps include expanding cohorts to increase statistical power, extending follow-up to evaluate durability out to a year, initiating monotherapy cohorts in obese diabetic patients, and adding combination cohorts with GLP therapies beyond tirzepatide. Anzalone also said Arrowhead plans withdrawal-style “maintenance” studies to evaluate whether INHBE or ALK7 therapy could help maintain weight loss after GLP treatment is removed.
During Q&A, Anzalone said Arrowhead is “not looking to partner” the obesity programs at this time, arguing the company can execute the next phase of development and create more value by keeping the assets wholly owned.
CNS platform and 2026 milestones
Arrowhead also discussed its CNS-targeting TRiM platform designed to enable brain delivery via subcutaneous injection using a transferrin targeting ligand linked to an siRNA molecule. Anzalone said animal studies have shown deep and durable knockdown across brain regions with a favorable safety profile and what he described as a roughly 10x safety margin versus the expected efficacious human dose in non-human primates and rodent studies.
The company’s first wholly owned CNS candidate is ARO-MAPT, designed to silence MAPT (tau). Arrowhead is currently conducting a phase 1/2A study and plans to monitor tau reduction through cerebrospinal fluid sampling. Anzalone said early readouts are expected toward the end of the third quarter of 2026, which he framed as a proof-of-concept milestone both for ARO-MAPT and for systemic CNS delivery more broadly. In discussing competitive approaches, Anzalone contrasted subcutaneous systemic delivery with intrathecal administration used by others and suggested that successful subcutaneous delivery could be disruptive.
Looking ahead, Arrowhead outlined 2026 milestones including its first full year of Rudemplo sales in FCS, SHTG phase 3 readouts and a planned sNDA, initial clinical data for ARO-Dimer-PA in the second half of 2026 (likely toward the end of Q3), additional obesity program updates throughout 2026, and early ARO-MAPT data in the second half of 2026.
On cash management, Anzalone said the company has not yet provided guidance on when it expects to reach breakeven, adding that he expects Arrowhead may do so sometime in 2026. He emphasized that current and expected cash sources provide “plenty of cash” to advance and, in several cases, potentially launch key programs independently in the U.S.
About Arrowhead Pharmaceuticals (NASDAQ:ARWR)
Arrowhead Pharmaceuticals, Inc is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics. Since its founding in 2008, Arrowhead has leveraged its proprietary delivery platform—known internally as the Advanced RNAi Compound (ARC) technology—to silence disease-causing genes in patients suffering from genetically defined diseases. The company’s approach aims to offer durable, targeted treatments across a range of therapeutic areas.
The company’s pipeline includes multiple candidates in various stages of development.
