NewAmsterdam Pharma Company (NAMS) Study Update summary

Study design and objectives

• Phase 3, randomized, double-blind, four-arm, placebo-controlled TANDEM trial evaluated a fixed-dose combination of obicetrapib 10 mg and ezetimibe 10 mg in 407 patients with ASCVD, HeFH, or multiple ASCVD risk factors whose LDL-C was not adequately controlled despite maximally tolerated lipid-lowering therapy.

• Patients were randomized 1:1:1:1 to receive the fixed-dose combination, obicetrapib monotherapy, ezetimibe monotherapy, or placebo for 84 days.

• The study had four co-primary endpoints comparing the combination to placebo, ezetimibe alone, obicetrapib alone, and obicetrapib alone to placebo, with percent change in LDL-C from baseline at day 84 as the primary endpoint.

• Baseline demographics: mean age ~67 years, 44% female, 83% White, mean BMI ~32 kg/m², 71–74% on high-intensity statin, mean baseline LDL-C 97 mg/dL.

Key efficacy results

• The fixed-dose combination achieved all co-primary endpoints, with a statistically significant LS mean LDL-C reduction of 48.6% versus placebo at day 84 (p<0.0001), and over 70% of patients reaching LDL-C <55 mg/dL.

• The combination showed an 18.5% greater LDL-C reduction than expected from monotherapies, supporting a synergistic effect.

• Over 60% of patients on the combination achieved >50% LDL-C reduction, and 80% achieved LDL-C <70 mg/dL.

• Significant Lp(a) reductions: fixed-dose combination -62.9% to -63% versus placebo; obicetrapib monotherapy -56% to -56.2%.

• Efficacy was consistent across phase I, II, and III studies, with mean LDL-C reductions aligning closely.

Lipoprotein(a) and other lipid parameters

• Lp(a) lowering was consistent with prior studies and is considered a key differentiator from other LDL-lowering drugs.

• No synergy was observed for Lp(a) lowering between the combination and monotherapy; reductions appeared independent.

• ApoB and non-HDL reductions were similar to previous trials and will be reported at future conferences.