Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — ObesityWeek 2025
21 slides from Wave Life Sciences's conference presentation, Oct 31, 2025
Slide 1: ObesityWeek, November 4-7, 2025
ObesityWeek, November 4-7, 2025 Wave Life Sciences RNA interference INHBE biology and obesity INLIGHT clinical program Veeva code: GBL-INHBE-2500002 | Date of preparation: October 31 2025
Slide 2: Company overview
Wave Life Sciences Company overview 2
Slide 3: We are an RNA medicines company
We are an RNA medicines company focused Wave Life Sciences on delivering transformational therapies for people with serious and life-altering diseases 3
Slide 4: Wave has driven foundational advances in nucleic acid chemistry
Wave has driven foundational advances in nucleic acid chemistry to expand platform technologies and develop the next generation of RNA therapeutics Further information can be found in recent platform publications Silencing (RNase H and Ago2) Splicing Editing 4 Selected Wave publications shown above
Slide 5: Wave's best-in-class multimodal platform
Wave’s best-in-class multimodal platform Silencing Splicing Editing Degradation of RNA transcripts to Restoration of RNA transcripts to Efficient editing of RNA bases to restore turn off protein production1,2 turn on protein production3 or modulate protein production4,5 Antisense siRNA RISC Spliceos
Slide 6: PRISM platform enables rational drug design
PRISM® platform enables rational drug design O 5′ B B B Base O - 3′ 2′ XX O R R R 2′-Ribose P O O 5′ B Stereochemistry and O X backbone modification 3′ 2′ O R R Phosphoryl guanidine PO: Phosphodiester PS: Phosphorothioate PN: Phosphoryl guanidine 6
Slide 7: Properties of chimeric PS/PN/PO oligonucleotide backbones compared with PO
Properties of chimeric PS/PN/PO oligonucleotide backbones compared with PO Chemical impact • Reduced number of charges Biological impact • Hydrophobic • Differential enzyme recognition • Chiral center • Enhanced potency, durability, and tissue • Chimeric backbone exposure in mice compared with contr
Slide 8: Robust, diversified RNA medicines pipeline including first-in-class RNA editing and RNAi programs
Robust, diversified RNA medicines pipeline including first-in-class RNA editing and RNAi programs IND / CTA Enabling Patient population Program Discovery Clinical Rights Studies (US & Europe) RNA EDITING WVE-006 (GalNAc) GSK exclusive 200K SERPINA1 (AATD) global license WVE-008 (GalNAc) 100% global
Slide 9: RNA interference
RNA interference WAVE LIFE SCIENCES
Slide 10: Oligonucleotide-directed gene silencing by RNA interference
Oligonucleotide-directed gene silencing by RNA interference RISC mRNA decay cascade siRNA mRNA Endogenous Decreased AGO2 protein production 10 AGO2: argonaute 2; RISC: RNA-induced silencing complex
Slide 11: WVE-007 is an investigational GalNAc-siRNA that targets INHBE mRNA
WVE-007 is an investigational GalNAc-siRNA that targets INHBE mRNA GalNAc-mediated delivery to hepatocytes Endosomal release enables siRNA-mediated mRNA degradation and receptor recycling GalNAc-siRNA RISC GalNAc binds to ASGR siRNA antisense strand mRNA ASGR Endosomal Endocytosis release Receptor s
Slide 12: INHBE biology and obesity
INHBE biology and obesity WAVE LIFE SCIENCES 12
Slide 13: Human INHBE loss-of-function variant carriers have a healthy metabolic profile
Human INHBE loss-of-function (LoF) variant carriers have a healthy metabolic profile Display favorable metabolic traits Lower risk of T2D and CHD Waist-to-hip ratio T2D adjusted for BMI CHD Serum 0.50 0.75 1.00 1.25 1.50 triglycerides Odds ratio HDL-c Lower risk Higher risk (vs. noncarriers) (vs. no
Slide 14: Activin E is a lipolysis suppressor upregulated in obesity
Activin E, the protein product of INHBE, is a lipolysis suppressor that is upregulated in obesity Healthy weight Obesity Overnutrition Albumin-bound fatty acids Albumin-bound fatty acids Liver TG Liver TG INHBE mRNA INHBE mRNA Lipolysis Lipolysis Activin E Activin E Normal Activin E keeps fat burnin
Slide 15: How INHBE GalNAc-siRNA might address obesity-associated metabolic disease
How INHBE GalNAc-siRNA might address obesity-associated metabolic disease Release of dimerized Activin E binds to and INHBE subunits creates the activates ACVR1C (ALK7) Adipose lipolysis hepatokine Activin E receptor in adipose tissue is blocked Activin E Activin E Increased abdominal adiposity lead
Slide 16: Advancing WVE-007 as a novel, long-acting, muscle-sparing approach for obesity
Advancing WVE-007 as a novel, long-acting, muscle-sparing approach for obesity WVE-007 is an investigational GalNAc-siRNA that is designed to target INHBE to treat overweight and obesity Adults with obesity have a higher risk for Data from human genetics2-4 and many serious health conditions1 precli
Slide 17: INLIGHT clinical program
INLIGHT clinical program WAVE LIFE SCIENCES 17
Slide 18: INLIGHT: Phase 1 trial of WVE-007 in adults with overweight or obesity
Menu Back Next INLIGHT: Phase 1 trial of WVE-007 in adults living with overweight or obesity who are otherwise healthy Randomized, double-blind, placebo-controlled (3:1) study of ascending doses of WVE-007 Trial design SAD Cohort 5 MAD Cohort 3 • Objective: Assess dose safety, tolerability, PK, and
Slide 19: Multiple near-term anticipated data updates for WVE-007
Menu Back Next Multiple near-term clinical anticipated data updates for WVE-007, including body weight and body composition 4Q 2025 1Q 2026 2Q 2026 600 mg 3 month follow-up (n=32) 400 mg 3 month follow-up (n=32) 6 month follow-up (n=32) 240 mg 3 month follow-up (n=32) 6 month follow-up (n=32) 9 mont
Slide 20: Preclinical data support WVE-007 across multiple treatment settings
Menu Back Next Preclinical data support the use of WVE-007 across multiple treatment settings, with potential for 1-2x per year dosing Monotherapy Add-on to GLP-1 RA Maintenance WVE-007 in addition to WVE-007 for patients who stop WVE-007 as a single agent GLP-1 RA therapy treatment with GLP-1 RA th
Slide 21: Wave Life Sciences: Reimagine possible.
WAVE LIFE SCIENCES Reimagine possible.