Wave Life Sciences (WVE) Update / Briefing Transcript

Summary of Wave Life Sciences (WVE) Update / Briefing September 03, 2025 Company Overview - Company: Wave Life Sciences (WVE) - Focus: Development of therapies for Alpha-1 Antitrypsin Deficiency (AATD) and RNA editing technologies Key Industry Insights - AATD Overview: AATD is caused by the aggregation of mutant ZAAT protein in the liver and a lack of functional AAT in the lungs, leading to severe lung and liver diseases, particularly in homozygous PIZZ individuals [1][2] - Current Treatments: Existing treatments are limited to weekly IV augmentation therapy, which does not adequately address the acute phase response during exacerbations [1][2] Core Points and Arguments - WVE-006 Development: WVE-006 aims to correct the Z mutation, increasing circulating levels of wild type MAAT protein and reducing mutant ZAAT protein aggregation in the liver [4][5] - Clinical Trials: The Restoration 2 clinical trial is evaluating the safety, tolerability, and pharmacokinetics of WVE-006 in individuals with AATD [6][8] - Safety Profile: WVE-006 has shown a favorable safety profile with no serious adverse events reported across all doses tested [9][10] - Biomarker Results: In the single and multiple dose cohorts, mean max total AAT levels reached 12.9 and 11.9 micromolar, respectively, with MAAT protein levels increasing significantly [10][11] - Dynamic Response: WVE-006 demonstrated the ability to restore dynamic physiological AAT production during acute phase responses, a first for AATD therapies [15][17] Additional Important Insights - RNA Editing Technology: The proprietary RNA editing technology used in WVE-006 allows for efficient and durable editing, which is crucial for achieving therapeutic effects [19][20] - Partnership with GSK: GSK's involvement is expected to enhance the development and commercialization of WVE-006, leveraging their expertise in respiratory medicine [18][19] - Future Programs: Wave Life Sciences is advancing additional RNA editing programs, including PNPLA3 for liver disease, with a CTA filing expected in 2026 [19][20] - Long-term Studies: There are plans for long-term extension cohorts to gather additional data on repeat dosing and acute phase responses [87][88] Conclusion - Transformative Potential: WVE-006 has the potential to transform the treatment landscape for AATD by enabling patients to produce protective AAT protein when needed, addressing both lung and liver manifestations of the disease [17][18] - Next Steps: The company anticipates sharing further data from ongoing trials in early 2026, which will provide more insights into the efficacy and safety of WVE-006 [22]