Arrowhead Pharmaceuticals, Inc. · NASDAQ:ARWR

Arrowhead Pharmaceuticals — American Heart Association Scientific Sessions 2023

14 slides from Arrowhead Pharmaceuticals's conference presentation, 2023

1. Slide 1: ARO-APOC3 Silences APOC3 and Reduces TG in Patients With SHTG: SHASTA-2 Results

   #AHA23 ARO-APOC3, an Investigational RNAi Therapeutic, Silences APOC3 and Reduces TG to Near Normal Levels in Patients With SHTG: SHASTA-2 Study Results Daniel Gaudet, MD, PhD ECOGENE-21 and Dept of Medicine, Université de Montréal on behalf of the SHASTA-2 Study Team

2. Slide 2: Financial Disclosures

   Financial Disclosures Presenter D Gaudet reports grants and/or honoraria from Alnylam, Amgen, Arrowhead, AstraZeneca, Boehringer- Ingelheim, CRISPR Therapeutics, Dalcor Pharma, Eli Lilly, Esperion, Ionis, Kowa, Novartis, Pfizer, Regeneron, Sanofi, Ultragenyx and Verve Therapeutics. Co-Authors D Pall

3. Slide 3: Goal Of SHTG Therapy Is To Reduce TGs Below Pancreatitis Risk

   Goal Of SHTG Therapy Is To Reduce TGs Below Pancreatitis Risk ▪ Severe hypertriglyceridemia (SHTG) is characterized by circulating triglycerides (TG) > 500 mg/dL1-3 ▪ In the United States (US), there are ~2-4 million adults with SHTG4-5 ▪ The etiology of SHTG is multi-factorial4-6 • Risk factors can

4. Slide 4: Key Features Of Using RNAi As A Therapeutic Modality

   Key Features Of Using RNAi As A Therapeutic Modality RNAi is a natural process that uses short fragments of RNA molecules to interfere with mRNA translation into associated proteins. High Specificity: Allowing to suppress the expression of a specific gene Potent Activity: Deep and consistent silenci

5. Slide 5: Plozasiran Is An Investigational RNAi Therapeutic Targeting ApoC3

   Plozasiran (ARO-APOC3) Is An Investigational RNAi Therapeutic Targeting ApoC3, A Key Mediator Of TG And Atherogenic Lipoproteins APOC31 Plozasiran APOC3 Inhibits TRL Catabolism and Hepatic Silencing of APOC3 Enables TRL Catabolism and Clearance Leading to Increased TGs Hepatic Clearance Leading to R

6. Slide 6: SHASTA-2: Double-blind, Phase 2b Placebo-Controlled, Dose Ranging Study

   SHASTA-2: A Double-blind, Phase 2b Placebo-Controlled, Dose Ranging Study Of Plozasiran In Subjects With SHTG Study Objectives: To evaluate safety and efficacy for lowering TG and atherogenic lipoproteins and severity/occurrences of AP in subjects with SHTG, and to explore optimal dosing Study Popul

7. Slide 7: Baseline Characteristics

   Baseline Characteristics Plozasiran Pooled Placebo 10 mg 25 mg 50 mg (N=60) (N=54) (N=55) (N=57) Mean (SD) age, years 56.2 (11.0) 53.0 (9.6) 56.0 (10.6) 54.3 (11.0) Female, n (%) 14 (23.3) 8 (14.8) 12 (21.8) 16 (28.1) White, n (%) 55 (91.7) 47 (87.0) 48 (87.3) 53 (93.0) Mean (SD) BMI, kg/m2 30.6 (3.

8. Slide 8: Substantial And Durable Decreases In Serum APOC3 Restoring TG Homeostasis

   Plozasiran Demonstrates Substantial And Durable Decreases In Serum APOC3 Restoring TG Homeostasis 40 APOC3a 1200 Triglycerides Placebo APOC3 mg/dL Mean (±SEM) 1000 Triglycerides mg/dL 10 mg Plozasiran 30 Median (Q1,Q3) 800 25 mg Plozasiran 50 mg Plozasiran 20 600 400 10 200 0 0 0 4 8 12 16 20 24 0 4

9. Slide 9: Most Subjects Achieved Triglyceride Levels < 500 mg/dL

   Most Subjects Treated With Plozasiran Achieved Triglyceride Levels < 500 mg/dL, Below the Risk Threshold For Acute Pancreatitis 400* Placebo 100 10 mg Plozasiran % Change from Baseline in Fasting 80 25 mg Plozasiran TG (mg/dL) at Week 24 60 50 mg Plozasiran 40 20 0 -20 -40 -60 -80 -100 Placebo Ploza

10. Slide 10: Decreases Remnant Cholesterol And Increases HDL-C

    Plozasiran Decreases Remnant Cholesterol And Increases HDL-C Remnant Cholesterola HDL-C Placebo 160 60 10 mg Plozasiran Remnant Cholesterol mg/dL HDL-C mg/dL Mean (± SE) 140 25 mg Plozasiran 120 50 50 mg Plozasiran Mean (± SE) 100 80 40 60 30 40 20 20 0 4 8 12 16 20 24 0 4 8 12 16 20 24 Study Week S

11. Slide 11: Impact On Additional Lipid Parameters

    Plozasiran Impact On Additional Lipid Parameters Non-HDL-C LDL-C LDL-C, UC mg/dL Median (Q1, Q3) 160 Total ApoB Non- HDL-C mg/dL Mean (± SE) 130 Total ApoB mg/dL Mean (±SE) 240 140 220 120 200 120 110 180 100 160 100 80 140 60 90 120 100 40 80 0 4 8 12 16 20 24 0 4 8 12 16 20 24 0 4 8 12 16 20 24 St

12. Slide 12: Summary Of Adverse Events

    Summary Of Adverse Events Plozasiran TEAEs reported to date Pooled reflect the comorbidities Placebo 10 mg 25 mg 50 mg and underlying conditions (N=60) (N=54) (N=55) (N=57) of the study population TEAEs 42 (70.0) 41 (75.9) 35 (63.6) 48 (84.2) Serious TEAEs were not TEAEs occurring in ≥ 5 subjects​ r

13. Slide 13: Plozasiran Reduces Triglycerides And Triglyceride Rich Lipoproteins in SHTG

    Plozasiran Reduces Triglycerides And Triglyceride Rich Lipoproteins in Subjects With SHTG ▪ Plozasiran durably decreases serum APOC3, TGs, and remnant cholesterol while increasing HDL-C at 24 weeks for all dose levels: • APOC3 reductions to -79% • Remnant cholesterol reductions to -63% • TG reductio

14. Slide 14: Thank You

    THANK YOU WE WOULD LIKE TO THANK THE PATIENTS AND CAREGIVERS WHO PARTICIPATED IN THIS STUDY #AHA23

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