Core Insights - Novartis announced positive results from the V-DIFFERENCE Phase IV study, demonstrating the efficacy of Leqvio (inclisiran) in lowering LDL-C levels in patients with high cholesterol who did not meet guideline-recommended targets [1][2][4] Group 1: Study Results - After 90 days of treatment, 85% of patients on Leqvio achieved their LDL-C targets compared to 31% on placebo, with statistical significance (p<0.0001) [2][3] - Significant benefits were observed as early as 30 days, with 81% of patients achieving LDL-C targets [2] - Leqvio reduced LDL-C levels by an average of 59% after 360 days, outperforming placebo by 35% (p<0.0001) [3][9] Group 2: Patient Outcomes - The study showed that patients receiving Leqvio were 43% less likely to experience muscle-related adverse events compared to those on placebo (p<0.0001) [3][7] - Improvements in pain-related quality-of-life scores were also reported among patients treated with Leqvio [3] Group 3: Clinical Significance - V-DIFFERENCE is the largest LDL-C lowering study with Leqvio to date, focusing on patient-centered outcomes [3][10] - The study included 1,770 individuals, randomized to receive either Leqvio plus LLT or placebo plus LLT [8][9] Group 4: Broader Context - Leqvio is the first and only small interfering RNA therapy approved in over 100 countries, including the US, EU, Japan, and China [5][6] - The VictORION clinical program, which includes V-DIFFERENCE, encompasses over 60,000 patients across more than 30 trials, aiming to expand evidence for LDL-C reduction [10]

Summary of New Amsterdam Pharma Company (NAMS) Conference Call - July 30, 2025 Company Overview - **Company**: New Amsterdam Pharma Company (NAMS) - **Focus**: Development of obacetropib for Alzheimer's disease and its potential as a disease-modifying therapy Key Industry Insights - **Alzheimer's Disease**: The conference highlighted the significance of obacetropib in potentially slowing or preventing Alzheimer's disease progression, particularly in APOE4 carriers, a high-risk genetic group for both Alzheimer's and cardiovascular diseases [6][7][9] - **Biomarkers**: The presentation emphasized the importance of pTau217 as a biomarker for Alzheimer's disease progression, showing that obacetropib significantly reduced pTau217 levels compared to placebo [12][13][14][18] Core Findings and Data - **Clinical Trial Results**: - In the Broadway trial, obacetropib resulted in a statistically significant reduction in pTau217 progression over 12 months, with a 1.99% increase in the treatment group versus nearly 5% in the placebo group (p=0.019) [12] - In APOE4 carriers, the increase was 1.45% with obacetropib compared to 7.19% with placebo (p=0.022) [12] - In APOE4 homozygotes, a 20.5% absolute difference in pTau217 progression was observed (p=0.01) [13] - **Comprehensive Biomarker Improvement**: The trial showed favorable trends across multiple Alzheimer's biomarkers, including GFAP and neurofilament light (NfL), indicating a potential for disease modification [15][22][24] Potential Market Impact - **Differentiation from Existing Therapies**: Obacetropib is positioned as a first-in-class oral therapy that not only lowers LDL cholesterol but also addresses Alzheimer's pathology, which is not achieved by current anti-amyloid therapies [22][25] - **Target Population**: Approximately 25% of the general population are APOE4 carriers, representing a significant market opportunity for obacetropib as a preventive treatment [23][36] Regulatory and Development Considerations - **Future Studies**: The company plans to engage with the FDA regarding the potential for obacetropib to be used in primary prevention of Alzheimer's disease, with ongoing trials like PREVAIL involving 9,500 patients [54][59] - **Biomarker as Endpoint**: There is ongoing discussion about the potential for pTau217 to be accepted as a registrational endpoint, although current FDA stance may require cognitive outcome data [63][70] Expert Panel Insights - **Panelists' Perspectives**: Experts highlighted the significance of the findings, particularly the safety profile of obacetropib and its potential for early intervention in high-risk populations [26][31][41] - **Preventive Neurology**: The need for a precision medicine approach in Alzheimer's treatment was emphasized, advocating for the use of biomarkers to personalize care [34][38] Conclusion - **Strategic Positioning**: New Amsterdam Pharma is positioned to lead in the development of innovative therapies for Alzheimer's disease, with obacetropib showing promise as a unique oral treatment that addresses both cardiovascular and neurodegenerative risks [22][25][54]