Benzinga | Aug 31, 2020 05:43AM EDT

Arrowhead Presenting Positive New Phase 1/2 Clinical Data Monday on Cardiometabolic Candidates ARO-APOC3 and ARO-ANG3 at European Society of Cardiology Congress 2020

Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR) today announced the presentation of positive new Phase 1/2 clinical data on two RNAi-based cardiometabolic candidates, ARO-APOC3 targeting apolipoprotein C-III (APOC3) being developed as a treatment for patients with hypertriglyceridemia, and ARO-ANG3 targeting angiopoietin like protein 3 (ANGPTL3) being developed as a treatment for mixed dyslipidemias. The data were presented in back-to-back oral presentations at the European Society of Cardiology (ESC) Congress 2020.

Javier San Martin, M.D., chief medical officer at Arrowhead, said: "These positive results from the healthy volunteer, repeat-dose portion of the Phase 1/2 clinical studies of our cardiometabolic candidates, ARO-APOC3 and ARO-ANG3, strongly support our plans to rapidly advance both drug candidates into later stage development. Both RNAi-based investigational therapies demonstrated three important characteristics: First, they had favorable safety and tolerability profiles, consistent with our other TRiM(tm)-enabled candidates; second, they achieved high levels of pharmacologic activity against their respective targets, with a long duration of effect that may enable an attractive and convenient dosing interval of once every 4 or 6 months; and third, inhibition of the targets led to favorable improvements in multiple lipid parameters. These are precisely the traits we were looking for and further support our belief that RNAi is the optimal mechanism to inhibit APOC3 and ANGPTL3. We are excited about the promise of ARO-APOC3 and ARO-ANG3 as potential new treatment options for large populations of currently underserved patients with cardiovascular disease risk from hypertriglyceridemia and mixed dyslipidemias. We also look forward to presenting additional data from studies in various patient populations at the National Lipid Association and American Heart Association meetings later this year."

ARO-APOC3 Presentation Details:

Title: RNA Interference Targeting Apolipoprotein C-3 with ARO-APOC3 in Healthy Volunteers Mimics Lipid and Lipoprotein Findings Seen in Subjects with Inherited Apolipoprotein C-3 DeficiencyAuthors: Christian Schwabe, et al.Presenter: Christie M. BallantyneType: Oral PresentationDate and Time: August 31, 2020, at 10:50 CESTKey points presented include the following:

In normal volunteers, repeat doses of ARO-APOC3, an investigational RNAi therapeutic that silences APOC3 mRNA, resulted in:Reduction in APOC3Maximal mean fasting lipid, lipoprotein, and apolipoprotein changes of:-75% for triglycerides (TG)-25% for low-density lipoprotein cholesterol (LDL-C)-33% for apolipoprotein B (ApoB)+75% for high-density lipoprotein cholesterol (HDL-C)ARO-APOC3 had a favorable safety and tolerability profileAPOC3 inhibition produced expected favorable lipid changes, with reduced TG and LDL-C and increased HDL-CARO-ANG3 Presentation Details:

Title: RNAi Inhibition of Angiopoietin-like Protein 3 (ANGPTL3) with ARO-ANG3 Mimics the Lipid and Lipoprotein Profile of Familial Combined HypolipidemiaAuthors: Gerald F. Watts, et al.Presenter: Gerald F. WattsType: Oral PresentationDate and Time: August 31, 2020, at 11:00 CESTKey points presented include the following:

In normal volunteers, repeat doses of ARO-ANG3, an investigational RNAi therapeutic that silences ANGPTL3 mRNA, demonstrated:Dose-dependent reduction in fasting ANGPTL3Maximal mean reductions in fasting lipid, lipoprotein, and apolipoprotein concentrations of:-71% in TG-50% in LDL-C-42% in ApoB-34% in non-HDL-C-47% in HDL-CLipid, lipoprotein, and apolipoprotein reductions sustained to week 16ARO-ANG3 had a favorable safety and tolerability profileANGPTL3 inhibition has the potential to treat mixed dyslipidemia and decrease residual risk in patients with cardiovascular disease on guideline-recommended standard of care