NewAmsterdam Pharma Company (NAMS) Investor update summary

Clinical development and trial progress

• PREVAIL trial for obicetrapib marked two years since last patient enrollment, with blinded data showing encouraging trends and lower than anticipated MACE rates from year one to year two, compared to historical LDL-C outcome studies.

• Interim analysis is scheduled for Q4 2026, aligning with a minimum 2.5-year follow-up and expected results in Q1 2027; if not stopped for efficacy, trial completion is anticipated by end of 2027.

• Expansion of the primary endpoint to total coronary events and a longer median follow-up increases statistical power for the primary 4-point MACE endpoint.

• Event rates and trends in PREVAIL closely mirror those observed in the BROADWAY trial, with similar baseline characteristics and risk profiles, supporting the validity of the ongoing study.

• PREVAIL is a larger, longer trial (N=9541, 54 months) focused on measuring MACE benefit, while BROADWAY (N=2532, 13 months) focused on LDL-C endpoints.

Interim analysis rationale and statistical considerations

• Interim analysis is justified by encouraging blinded data and is expected to be sufficiently powered to detect a benefit, with minimal statistical penalty for conducting the interim.

• Stopping rules for the interim are based on p-values, not hazard ratios, and the DSMB has discretion to stop or continue the trial.

• If the interim does not stop the trial, only the continuation will be disclosed; no further data will be shared until final analysis.

• The interim could allow for earlier market entry by about one year if efficacy is demonstrated, with ongoing discussions with the FDA regarding regulatory strategy.

• Management highlights uncertainties in clinical development, including whether observed trends in BROADWAY will predict PREVAIL outcomes.

Comparative insights and mechanistic considerations

• PREVAIL is designed as a higher-risk trial with higher baseline LDL, more diabetics, and more post-MI patients, making it comparable to the upper tertile of REVEAL and other major trials.

• Lower event rates in PREVAIL are attributed to a likely treatment effect, supported by consistent trends across all MACE components and favorable comparisons to placebo arms in other CETP and lipid-lowering trials.

• Intensive LDL lowering and CETP inhibition are hypothesized to reduce small, atherogenic LDL particles, which may contribute to the observed benefits.

• PREVAIL’s design and event accrual ensure robust power for both primary and secondary endpoints, with FDA labeling now harmonized to allow inclusion of composite endpoints even if individual components are not statistically significant.

• BROADWAY showed a 21% observed reduction in MACE-4, with potential contributions from LDL-C, LDL-P, and Lp(a) reductions.