Ionis Pharmaceuticals, Inc. · NASDAQ:IONS
Ionis Pharmaceuticals — Technical Presentation (June 2026)
15 slides from Ionis Pharmaceuticals's technical presentation, Jun 6, 2026
Slide 1: Olezarsen Markedly Reduces Triglycerides & Risk of Pancreatitis in sHTG Patients with Diabetes
ApoC3 Inhibitor Olezarsen Markedly Reduces Triglycerides & Risk of Pancreatitis in Severe Hypertriglyceridemia Patients with Diabetes Mellitus: Insights from CORE-TIMI 72a and CORE2-TIMI 72b Yu Mi Kang, Nicholas A. Marston, Veronica J. Alexander, Thomas A. Prohaska, Xinhui Ran, Sabina A. Murphy, Eri
Slide 2: Background: sHTG, APOC3, & olezarsen
Background sHTG, APOC3, & olezarsen • Severe hypertriglyceridemia (sHTG), defined as triglycerides (TGs) ≥500 mg/dL (5.65 mmol/L) carries an increased risk of acute pancreatitis • Apolipoprotein C-III (APOC3) inhibits: • lipoprotein lipase (LPL), a key enzyme in TG metabolism • hepatic uptake of TG-
Slide 3: CORE–TIMI 72a & CORE2–TIMI 72b Study design
CORE–TIMI 72a & CORE2–TIMI 72b Study design (identical) Primary endpoint: placebo-adjusted % change in triglycerides at 6 months Secondary endpoints include % change in other lipid parameters and acute pancreatitis 3 Marston NA, Bergmark BA et al. N Engl J Med 2026;394:429–441
Slide 4: Primary endpoint: placebo-adjusted % change in TG at 6 months
CORE–TIMI 72a & CORE2–TIMI 72b Primary endpoint: placebo-adjusted % change in TG at 6 months from baseline CORE-TIMI 72a CORE2-TIMI 72b Olezarsen lowered plasma TG levels by ~49-72%, compared to placebo 4 Marston NA, Bergmark BA et al. N Engl J Med 2026;394:429–441
Slide 5: Secondary endpoint: Acute pancreatitis over 12 months
CORE–TIMI 72a & CORE2–TIMI 72b Secondary endpoint: Acute pancreatitis over 12 months (pooled analysis) Abbreviations: ARR, absolute risk reduction; NNT, number needed to treat; RR, rate ratio Olezarsen reduced the rate of acute pancreatitis by 85%, compared to placebo 5 Marston NA, Bergmark BA et al
Slide 6: Background & Objectives: sHTG & DM
Background & Objectives sHTG & DM • Insulin resistance, a hallmark of type 2 diabetes mellitus (DM), is a common non-genetic driver of TG dysregulation • Both sHTG & DM are independently associated with high risk for acute pancreatitis (AP), a potentially life-threatening complication • Therefore, p
Slide 7: Methods
Methods • Modified intention-to-treat population (≥1 dose study medication) • Baseline DM was defined as at least one of: • Investigator-reported history of DM (dedicated eCRF field) • HbA1c ≥6.5% • Use of glucose-lowering medications in the absence of a non-DM indication • Changes in fasting lipid
Slide 8: Baseline Characteristics: DM vs No DM
Baseline Characteristics DM vs No DM DM No DM DM Characteristic Characteristic (N=689) (N=372) (N=689) Age (years) 56 50 Glucose-lowering medications Female 27.6% 16.1% Insulin 36.0% Body mass index (kg/m2) 31.6 30.3 Basal insulin 32.7% History of ASCVD 30.3% 16.9% Rapid-acting insulin 22.1% History
Slide 9: TG-Lowering Efficacy of Olezarsen by Baseline DM
TG-Lowering Efficacy of Olezarsen by Baseline DM At 6 months Error bars indicate 95% confidence intervals; P<0.0001 for all comparisons vs. placebo; P-interaction=0.93 9
Slide 10: Efficacy of Olezarsen in Acute Pancreatitis Prevention
Efficacy of Olezarsen in Acute Pancreatitis Prevention Total event analysis over 12 months, pooled olezarsen DM No DM ARR = 6.6% (NNT = 16) ARR = 3.0% (NNT = 33) Rate ratio = 0.19 (0.07-0.56), P<0.001 Rate ratio = N/A Abbreviations: ARR, absolute rate reduction; CI, confidence interval; NNT, number
Slide 11: Glycemic Impact of Olezarsen by DM Status: HbA1c
Glycemic Impact of Olezarsen by DM Status HbA1c, pooled olezarsen Placebo (PBO) Olezarsen DM PBO-adjusted LSM 𝚫: 0.26% (95% CI 0.10-0.43)* No DM PBO-adjusted LSM 𝚫: 0.13% (95% CI 0.07-0.19)* Estimates at each time point are presented as medians, with error bars indicating 95% confidence…
Slide 12: Glycemic Impact of Olezarsen by DM Status: Fasting Glucose
Glycemic Impact of Olezarsen by DM Status Fasting plasma glucose, pooled olezarsen Placebo (PBO) Olezarsen PBO-adjusted LSM 𝚫: 12.1 mg/dL (95% CI 2.9-21.3)* DM No DM PBO-adjusted LSM 𝚫 : 2.2 mg/dL (95% CI -1.1-5.6); P=NS Estimates at each time point are presented as medians, with error bars…
Slide 13: Glycemic Impact of Olezarsen by DM Status: HOMA-IR
Glycemic Impact of Olezarsen by DM Status HOMA-IR, pooled olezarsen Placebo (PBO) Olezarsen PBO-adjusted LSM 𝚫: 1.5 (95% CI -0.6-3.6); P=NS DM No DM PBO-adjusted LSM 𝚫: -0.8 (95% CI -2.3-0.8); P=NS Estimates at each time point are presented as medians, with error bars indicating 95% confidence…
Slide 14: Limitations
Limitations • Changes in diabetes medications were not assessed in this study • Assessment of glycemic profile may not fully capture the extent of dysglycemia • Not designed to elucidate the mechanistic pathways underlying the glycemic change, but appears to be a class effect • Assessment of glycemi
Slide 15: Summary & Conclusions
Summary & Conclusions • In this high-risk population with severe HTG & DM, olezarsen; • Reduced TG levels by 58–65% on top of currently available lipid lowering therapies • Reduced acute pancreatitis events by 81%, with an absolute rate reduction of 6.6% ‒ Yielded a number needed to treat of 16 to p
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