Announcement • May 29
Arrowhead Pharmaceuticals Presents New Clinical Data on RNAi-based Obesity and MASH Candidate ARO-INHBE at EASL 2026 Arrowhead Pharmaceuticals, Inc. presented interim results from a Phase 1/2a clinical trial of ARO-INHBE, the company’s investigational RNA interference (RNAi) therapeutic being developed as a potential treatment for obesity and metabolic dysfunction-associated steatohepatitis (MASH). The data presented at the European Association for the Study of the Liver Congress (EASL 2026) demonstrate that ARO-INHBE treatment led to clinically meaningful reductions in liver fat as a monotherapy and in combination with low-dose tirzepatide, a GLP-1/GIP receptor co-agonist, in adults with obesity. Arrowhead is currently engaging with regulatory authorities on additional designs and endpoints for potential Phase 2 studies in MASH and obesity. The EASL 2026 poster may be accessed on the Events and Presentations page on the Investors section of the Arrowhead website. In participants with obesity, dose-dependent reductions in Activin E were observed following a single administration of ARO-INHBE, with a mean maximum reduction of 85.3% achieved with ARO-INHBE 400 mg and persistent effect beyond 3 months. Similar Activin E reductions were observed in participants with obesity and T2DM receiving two doses of ARO-INHBE (200 mg or 400 mg) in combination with tirzepatide 5 mg, demonstrating persistent effect through Week 24 with the potential for infrequent twice per year dose administration. Participants with obesity and baseline liver fat content (LFC) greater than 8% receiving 200mg or greater of ARO-INHBE monotherapy (n=10; baseline LFC 14.5±5.1%) had a placebo-adjusted post-dose LFC reduction of 44% (t-test: p < 0.01). ARO-INHBE in combination with low-dose tirzepatide (5 mg) resulted in enhanced reductions in visceral adipose tissue and LFC compared to tirzepatide alone in participants with obesity with or without T2DM. Longer exposure to ARO-INHBE resulted in continued improvements in visceral fat and LFC from Week 12 to Week 24. ARO-INHBE has been generally well tolerated to date as a monotherapy and in combination with tirzepatide in participants with obesity with and without type 2 diabetes. Most treatment emergent adverse events (TEAE) were mild in severity. No TEAEs led to study or study drug discontinuation. Injection site reactions were generally mild and self-limited. ARO-INHBE is designed to reduce the hepatic expression of the INHBE gene and its secreted gene product, Activin E. INHBE is a promising genetically validated target in which loss-of-function INHBE variants in humans are associated with improved fat distribution and lower risk of metabolic diseases, such as type 2 diabetes. Activin E acts as a ligand in a pathway that regulates energy homeostasis in adipose tissue. Inhibiting this pathway with investigational ARO-INHBE treatment has the potential to increase lipolysis, and reduce adipose hypertrophy and dysfunction, visceral adiposity, and insulin resistance. AROINHBE-1001 (NCT06700538) is a Phase 1/2a dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-INHBE in up to 78 adult volunteers with obesity. Part 1 of the study is designed to assess single and multiple doses of ARO-INHBE monotherapy, and Part 2 of the study is designed to assess ARO-INHBE in combination with tirzepatide, a subcutaneously administered GLP-1/GIP receptor co-agonist that has been approved in the United States and the European Union for management of type 2 diabetes mellitus since 2022 and weight management since 2023/2024 respectively. ARWR
Live News • May 28
Arrowhead Pharmaceuticals Advances RNAi Drug for Obesity and MASH With Promising Early Clinical Data Arrowhead Pharmaceuticals reported interim Phase 1/2a data for ARO-INHBE, its RNAi candidate for obesity and MASH, at the EASL 2026 congress.
The data showed clinically meaningful reductions in liver fat with ARO-INHBE used alone and in combination with low-dose tirzepatide.
The company is now in discussions with regulators regarding potential Phase 2 trial designs and endpoints in both MASH and obesity.
The key takeaway is that ARO-INHBE has moved from early safety and mechanism testing into a stage where regulators are being engaged on how to structure the next wave of trials, which can be an important step in a drug’s development path.
Investors may want to pay close attention to how those Phase 2 plans are shaped, including selected endpoints and combination strategies, as these choices can influence future timelines, costs and the range of potential patients targeted. Announcement • May 27
Arrowhead Pharmaceuticals Presents New Positive Clinical Data for Plozasiran at the 94th European Atherosclerosis Society Congress Arrowhead Pharmaceuticals, Inc. presented new positive clinical data for plozasiran supporting its use in patients with moderate-to-severe renal impairment or moderate hepatic impairment without the need for dose adjustment, and a case report suggesting that preconception exposure to plozasiran may be associated with sustained lowering of fasting triglyceride (TG) levels through the term of a pregnancy. The data were presented in two oral presentations at the 94th European Atherosclerosis Society (EAS) Congress, taking place in Athens, Greece from May 24-27. Plozasiran is a small interfering RNA (siRNA) medicine designed to reduce hepatic production of apolipoprotein C-III (APOC3) through targeted RNA interference. It received regulatory approval in the United States, China, Australia, and Canada as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS) and is currently being investigated in patients with severe hypertriglyceridemia (sHTG). Patients with FCS and sHTG often present with hepatic steatosis or renal impairment. Because the safety and tolerability of plozasiran in the setting of hepatic and/or renal impairment remains unknown, this study assessed the impact of hepatic or renal impairment on the pharmacokinetics, pharmacodynamics, and safety of a single 25 mg dose of plozasiran. Despite modest increases in plozasiran exposure, PD responses (APOC3 and TG reduction) were similar between control cohorts and those with moderate-to-severe renal or moderate hepatic impairment. In addition, plozasiran was generally safe and well-tolerated, with no new safety signals identified. Together, these data support the use of 25 mg plozasiran in patients with moderate-to-severe renal impairment or moderate hepatic impairment without dose adjustment. Future trials are needed to help further evaluate plozasiran safety in patients with advanced liver or renal disease. In an additional oral presentation, the company highlighted a patient case report that suggests that preconception exposure to plozasiran may be associated with sustained lowering of fasting TG levels throughout the term of a pregnancy, representing the second case report published on FCS patients in the PALISADE study who discontinued use of plozasiran prior to conception and achieved successful pregnancies. While additional data are needed to define the safety and efficacy of APOC3–targeted therapies during pregnancy, these findings are consistent with the prolonged pharmacodynamic effects of APOC3 inhibition reported in previous PALISADE studies. REDEMPLO (plozasiran) is the first and only siRNA treatment approved in these countries that has been studied in both genetically confirmed and clinically diagnosed patients living with FCS. REDEMPLO is a first-in-class siRNA therapeutic designed to suppress the production of apoC-III, a protein produced in the liver that raises triglyceride levels by slowing their breakdown and clearance. By targeting apoC-III with sustained silencing, REDEMPLO delivers significant reductions in triglyceride levels. REDEMPLO is self-administered via subcutaneous injection once every three months. The EMA CHMP has adopted a positive opinion recommending the European Marketing Authorization of REDEMPLO (plozasiran), which is already approved by the U.S. Food and Drug Administration, Health Canada, the Australian Therapeutic Goods Administration, and China’s National Medical Products Administration as an adjunct to diet to reduce triglycerides for adults with Familial Chylomicronemia Syndrome (FCS). Plozasiran is also being investigated in the SHASTA-3 (NCT06347003), SHASTA-4 (NCT06347016), and SHASTA-5 (NCT06880770) Phase 3 studies in adults with severe hypertriglyceridemia and the MUIR-3 (NCT06347133) Phase 3 study in adults with hypertriglyceridemia. In December 2025, plozasiran was granted Breakthrough Therapy designation by the U.S. FDA in severe hypertriglyceridemia.