Arrowhead Pharmaceuticals Announces New Phase 2 Data of Plozasiran Published in JAMA Cardiology and Presented at American College of Cardiology 73rd Annual Scientific Session & Expo - Seite 2

Safety and Tolerability

Plozasiran demonstrated a favorable safety profile in the SHASTA-2 study. The adverse event and serious adverse event profile were similar across treatment groups. Observed adverse events generally reflected the comorbidities and underlying conditions of the study population. All serious treatment emergent adverse events were deemed not related to plozasiran. The most common events occurring in 5 or more patients were COVID-19 infection, worsening glycemic control, diarrhea, urinary tract infection, and headache.

Details about the ACC.24 presentation are listed below.

American College of Cardiology 73rd Annual Scientific Session & Expo – April 6-8, 2024

Title: Plozasiran (ARO-APOC3), An Investigational RNAi Therapeutic, Demonstrates Profound and Durable Reductions in APOC3 and Triglycerides (TG) in Patients With Severe Hypertriglyceridemia (SHTG), SHASTA-2 Final Results
Date/Time: April 7, 2024, 9:00 a.m. EDT
Presenter: Daniel Gaudet MD, PhD
Session: Late-Breaking Clinical Trials II

Slides from the late-breaking oral presentation at ACC.24 may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website after the oral presentation concludes.

About SHASTA-2

SHASTA-2 (AROAPOC3-2001) is a double-blind, placebo-controlled Phase 2b study in adults with SHTG. Three dose levels of plozasiran (10 mg, 25 mg and 50 mg) were evaluated against placebo in 229 participants who had mean fasting triglycerides of greater than or equal to 500 mg/dL (5.65 mmol/L) at screening. Participants were randomly assigned in a 3:1 ratio to receive plozasiran or placebo. Each participant received subcutaneous injections on day 1 and week 12. The duration of the study was approximately 54 weeks from screening to the week 48 end-of-study examination. The primary objective of the study was to evaluate the safety and efficacy of plozasiran in adults with SHTG and to select a dosing regimen for later stage clinical studies in this patient population.

About Severe Hypertriglyceridemia

Severe hypertriglyceridemia (SHTG) is characterized by triglyceride (TG) levels greater than 500 mg/dL^1-3. Very severe forms (TG greater 880 mg/dl) include familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS)^4-6. SHTG significantly increases the risk of atherosclerotic cardiovascular disease (ASCVD) and acute pancreatitis (AP), often with recurrent attacks requiring repeat hospital admissions and worsening outcomes^1-3,6. AP risk is proportional to number, characteristics, and concentration of triglyceride rich lipoproteins (TRLs), particularly chylomicrons, and increases as TGs rise⁷. Limited treatment options exist to sustainably reduce TGs below the pancreatitis risk threshold^1-3.