Wave Life Sciences (NasdaqGM:WVE) FY Conference Transcript

Summary of Wave Life Sciences FY Conference Call Company Overview - Company: Wave Life Sciences (NasdaqGM: WVE) - Industry: RNA therapeutics, focusing on oligonucleotides and genomic medicine [2][3] Core Points and Arguments INHIBIN-E Obesity Program - Program Type: siRNA, GALAX siRNA program targeting obesity [4] - Mechanism: INHIBIN-E is a liver-expressed dimer that regulates lipolysis by binding to ALK7 on fat cells, acting as a brake on fat breakdown [5] - Clinical Evidence: Carriers of loss-of-function variants show healthier cardiometabolic profiles, including lower abdominal obesity and triglycerides [4] - Differentiation: Unlike GLP-1 agonists that focus on appetite regulation, INHIBIN-E directly targets fat cells, potentially leading to fat loss without affecting muscle [6][17] - Preclinical Data: Comparable weight loss to semaglutide, with a focus on fat loss, particularly visceral fat [6][8] - Dosing: Potential for once or twice a year dosing based on preclinical data [6] - Current Status: Phase one trial focusing on safety, tolerability, and target engagement, with upcoming data releases for different dosing cohorts [12][14] Alpha-1 Antitrypsin Deficiency (AATD) Program - Disease Overview: A rare disease affecting lung and liver, with current treatments limited to protein replacement and liver transplantation [27] - Mechanism: RNA editing approach to correct mutations at the RNA level, producing healthy M protein [28] - Clinical Data: Achieved significant conversion from C to M protein, with a 65% decrease in C protein levels and increases in M protein [30] - Unique Finding: Observed endogenous regulation of AAT levels, demonstrating the potential for better patient response during inflammatory events [31][33] DMD (Duchenne Muscular Dystrophy) Program - Program Type: Exon-skipping therapy for exon 53, targeting about 10% of DMD patients [58] - Clinical Data: High and consistent levels of dystrophin observed, with significant improvements in muscle pathology and clinical measures [59][61] - Differentiation: Unique stereochemistry and PN chemistry allow for better drug delivery and efficacy compared to competitors [62][63] Huntington's Disease Program - Program Type: Allele-selective ASO targeting the mutant Huntington allele while sparing the wild-type protein [70] - Clinical Data: Achieved a 46% knockdown of mutant Huntington with no effect on wild-type, correlating with slowing of caudate atrophy [74] - Regulatory Discussions: Engaging with regulators for potential accelerated approval based on observed endpoints [74] Emerging Pipeline and Future Directions - PLMP3 Program: Targeting liver disease with a large patient population, aiming for clinical trials in 2026 [54][55] - Broader Applications: Exploring RNA editing for extrahepatic diseases, with promising preclinical data [56] Important but Overlooked Content - Competitive Landscape: Comparison with competitors in the siRNA space, highlighting differences in dosing frequency and weight loss efficacy [24] - Regulatory Pathway: Plans to engage with regulators for AATD and other programs, indicating a proactive approach to market entry [50][51] - Market Potential: Emphasis on the large unmet need in obesity and liver diseases, positioning Wave Life Sciences for significant market opportunities [10][54] Upcoming Milestones - Near-term Catalysts: Data readouts for INHIBIN-E and AATD programs expected in Q4 and Q1, respectively [75]