NewAmsterdam Pharma Company N.V. (NAMS) Earnings

Management highlights

- Corporate Mission & Value Proposition - New mission to set a new standard of care for cardiometabolic disease, built on translating biologic insights to patient impact. - Obacetrapib is differentiated from other LDL-lowering therapies via multiple cardiovascular risk reduction effects beyond LDL lowering: Lp(a) reduction, HDL elevation, small dense LDL elimination, and reduced new-onset diabetes risk. - Company has raised 678 million in financing, sufficient to support launch preparations and trial completion, and has expanded to over 100 employees with new offices opened. - CMC team won the Green Chemistry Challenge Award and built a robust supply chain for future launch. - Regulatory & Market Context - Received a positive CHMP recommendation from the EMA for Obacetrapib, the first CETP inhibitor to gain major regulatory approval, with full approval expected in early Q4 and launch in the UK/Germany by end of 2024 via partner Menarini. - The global lipid-lowering market is growing rapidly: 37% global growth for PCSK9 inhibitor Repatha in the last year, with non-statin market growing ~20% year-over-year and branded lipid therapy growing over 30% annually. Updated guidelines have lowered target LDL to 55 mg/dL for high-risk patients, expanding the eligible patient population. - There are ~60 million underserved patients in the U.S. and EU who are either untreated or not at LDL goal on statin therapy, representing a large addressable market. - Clinical Pipeline Updates - **Prevail (cardiovascular outcomes trial for Obacetrapib):** The design was modified to add 20% more events by changing from urgent revascularization to total revascularization, refined endpoints to focus on LDL-driven outcomes (ischemic stroke only, coronary heart disease death instead of broad cardiovascular death), and re-powered to detect a 15% relative risk reduction (down from an original 20% target) to maximize trial success. Blinded event rates after the first year track closely to the Broadway Phase 3 trial, which showed a 21% relative risk reduction in four-point MACE, and management is encouraged that the trial will meet stopping rules at the December 2024 interim analysis, with data readout in Q1 2025. If the interim does not stop the trial, full follow-up through the end of 2027 will deliver sufficient power for a positive result. - **Rembrandt (fixed-dose combination plaque regression trial):** Fully enrolled with 323 patients across 50 sites in 7 countries. The trial evaluates non-calcified plaque burden change after 18 months of treatment, using newly FDA-approved CCTA imaging technology. Topline data expected at the end of 2027. - **Rubens (trial in type 2 diabetes/metabolic syndrome):** Nearing completion, database lock and data readout expected by the end of 2024. The trial evaluates Obacetrapib's effects on LDL, small dense LDL, and Lp(a) in this high-risk population, with potential to support label expansion. - **Spinoza (Alzheimer's prevention trial in APOE4 carriers):** Initiation planned for 2025, following encouraging Phase 2 data showing a 20% reduction in pTau217 (a key Alzheimer's biomarker) in APOE4 homozygotes treated with Obacetrapib. The trial targets prevention of cognitive decline in at-risk patients with abnormal biomarker levels. - Commercial Preparation - U.S. launch preparations are underway across three pillars: market preparation, product preparation, and organizational buildout. A senior experienced commercial leadership team has been assembled. Medical affairs has published 26 peer-reviewed papers, is active at major cardiology conferences with 40 presentations planned in 2024, and has engaged KOLs and payers. Two-thirds of primary care and cardiology clinicians report high intent to prescribe Obacetrapib, driven by its broader efficacy profile, favorable safety, and oral once-daily dosing.

Guidance

- Milestones: Rubens data readout by end of 2024; Prevail interim analysis data readout in Q1 2025; Rembrandt data expected at end of 2027; Spinoza trial initiation in 2025; EMA approval of Obacetrapib expected in early Q4 2024, with Menarini launch in UK/Germany in late Q4 2024. - Management maintained that Prevail is sufficiently powered to detect a 15% relative risk reduction after design modifications, and is encouraged by blinded event tracking that meets or exceeds expectations for meeting interim stopping rules. - Management maintained that the company has sufficient cash (678 million) to complete all planned trials and support commercial launch preparation. - No significant change to overall regulatory or launch timelines was announced; the company plans to file for U.S. approval as early as possible after Prevail outcomes data is available.

Segment performance

No specific financial performance data for product segments was provided in this investor day transcript. The call focused on clinical pipeline updates, trial design, and commercial launch preparation, not historical or current segment financial results.

Risks & headwinds

- If the Prevail interim analysis does not meet pre-specified stopping rules, the trial will continue to full follow-up through the end of 2027, delaying commercial launch by approximately one year and exposing the company to additional execution risk. - The CETP inhibitor field has a history of prior failed clinical trials, and Prevail may fail to meet its primary endpoint even with modified design and additional power. - Horizon (the Novartis Lp(a) lowering outcomes trial) readout could create market uncertainty if it fails to show a benefit, even though management notes Prevail's benefit is driven primarily by LDL/non-HDL lowering independent of Lp(a). - Growing use of GLP-1s could potentially reduce overall event rates in the Prevail trial, though management notes GLP-1 drop-in rates are very low (~1% per year) in the trial, especially in non-U.S. sites, so the impact is expected to be negligible. - Newer oral PCSK9 inhibitors will launch before Obacetrapib, creating additional competitive pressure in the oral LDL-lowering market. - Pricing in Europe and the U.S. may be lower than historical injectable PCSK9 inhibitors, following the discounting seen for the newly launched oral PCSK9 from Merck.

Analyst Q&A

• Q: What explains the lower blinded event rates in year two of Prevail, and what is the powering cushion for the interim analysis? /

  A: Blinded first-year event rates match the identically designed Broadway trial, which had the same patient population, sites, adjudication, and DSMB. Imputing the Broadway placebo event rate into blinded Prevail data shows a Broadway-like relative risk reduction for both three-point and four-point MACE. There is powering cushion: the trial does not need to hit a 20% RRR to meet interim stopping rules, and can stop with a result closer to the 15% RRR seen with PCSK9 inhibitors. The decision to allow full follow-up to end of 2027 if needed was intentional to maximize the chance of a positive result, with no meaningful alpha penalty for the interim analysis.

• Q: What is the impact of a positive or negative Horizon (Lp(a)) readout on Prevail? /

  A: Prevail's success does not depend on Lp(a) lowering; the trial's expected benefit is already driven by the 40%+ LDL/non-HDL reduction seen in prior studies, which alone supports a 17-23% RRR consistent with Broadway. All that is needed from Horizon is biological confirmation that lowering Lp(a) reduces cardiovascular risk, which would be a positive for New Amsterdam regardless of whether Horizon meets its statistical endpoint. If Horizon fails to meet its endpoint or only shows a weak benefit, Obacetrapib would become the leading Lp(a)-lowering therapy available on the market.

• Q: How do you address recent failed CVOTs like Zeus, and what does Rubens data mean for labeling if positive? /

  A: The failed Zeus (inflammation inhibitor) trial has no connection to CETP inhibition, as the biological rationale and genetic evidence for CETP inhibition (multiple Mendelian randomization studies showing low CETP reduces heart attack risk) is robust. For Rubens, a positive trial would differentiate Obacetrapib in diabetic patients, where statins are known to increase diabetes risk by ~25%. Rubens data could support label expansion to highlight Obacetrapib's benefit in this large, high-risk population, supporting broader promotion to clinicians.

• Q: What can you tell us about the Rembrandt plaque trial after enrollment completion? /

  A: Rembrandt uses a newly FDA-approved CCTA imaging technology from Caristo, and enrolling patients with high baseline non-calcified plaque to maximize the chance of detecting a treatment effect. Preclinical data in humanized mouse models showed the Obacetrapib/ezetimibe combination reduced severe aortic plaque area by 98%, and the trial is expected to show large effect sizes in patients after 18 months of treatment. Positive plaque regression data would be a strong commercial differentiator, similar to how plaque imaging results drove PCSK9 uptake, and can support labeling and promotion.