Wave Life Sciences Ltd. · NASDAQ:WVE
Wave Life Sciences — 32nd European Congress on Obesity, ECO2025 (May 2025)
16 slides from Wave Life Sciences's conference presentation, May 13, 2025
Slide 1: siRNA-INHBE Silencing in Mice Confirms Human Genetic Data and Supports Next Generation Anti-Obesity Treatment
siRNA-INHBE Silencing in Mice Confirms Human Genetic Data and Supports the Vision for Next Generation Anti-Obesity Treatment Hsiu-Chiung (Ginnie) Yang, PhD SVP, Translational Medicine May 13, 2025 Presented at 32nd European Congress on Obesity, ECO2025
Slide 2: Forward-looking statements
Forward-looking statements This document contains forward-looking statements. All statements other than statements of historical facts contained in this document, including statements regarding possible or assumed future results of operations, preclinical and clinical studies, business strategies, r
Slide 3: Disclosures
Disclosures • Hsiu-Chiung (Ginnie) Yang, Wei Liu, Keith Bowman, Michael Byrne, Cynthia Caracta, Jigar Desai, Naoki Iwamoto, Pachamuthu Kandasamy, Tomomi Kawamoto, Anthony Lamattina, Fangjun Liu, Ken Longo, Khoa Luu, Subramanian Marappan, Lola Owen, Qianli Pan, Priyanka Prakasha, Himali Shah, Kuldeep
Slide 4: Wave's PRISM platform capitalizes on new genetic insights to modulate RNA expression
Wave’s PRISM® platform capitalizes on new genetic insights and harnesses the biological machinery in our cells to modulate RNA expression Silencing Splicing RNA Base Editing • Degradation of RNA transcripts to • Restore RNA transcripts and turn • Efficient editing of RNA bases to turn off protein pr
Slide 5: Human genetic data show heterozygous INHBE LoF carriers have a healthy metabolic profile
Human genetic data demonstrate that heterozygous INHBE LoF carriers have a healthy metabolic profile Heterozygous INHBE LoF carriers have lower risk of Type 2 Heterozygous INHBE LoF carriers have favorable traits: diabetes and CHD lower abdominal obesity, lower triglycerides, higher HDL-c Waist to h
Slide 6: Activin E is a lipolysis suppressor that is upregulated in obesity
Activin E is a lipolysis suppressor that is upregulated in obesity Healthy weight Obesity Overnutrition Albumin-bound fatty acids Liver TG Albumin-bound fatty acids Lipolysis Liver TG INHBE mRNA Lipolysis INHBE mRNA Activin E Activin E Normal Activin E keeps fat burning low during Increased Activin
Slide 7: How INHBE GalNAc-siRNA might address obesity-associated metabolic disease
How INHBE GalNAc-siRNA might address obesity-associated metabolic disease Release of dimerized INHBE Binds to and activates subunits creates hepatokine ACVR1C (ALK7) receptor in Block adipose Activin E adipose tissue lipolysis Activin E Activin E Increased abdominal adiposity leads to obesity, II II
Slide 8: INHBE GalNAc-siRNAs durably suppress weight gain in mice
INHBE GalNAc-siRNAs durably suppress weight gain in mice 0 1 2 3 4 5 Body Weight Body Weight 84 Days Weeks HFD Relative weight change ( % ) 30 25 PBS 0 14 28 84 HFD or siRNA Sac 20 INHBE-00002: Days CHOW (10 mg/kg, 15 Wave’s new siRNA (3 or 10 Sac SC) 10 design siRNA 5 * * DIO mg/kg, SC) Sac 0 * * S
Slide 9: A single dose of INHBE GalNAc-siRNA leads to weight loss driven by fat loss
A single dose of INHBE GalNAc-siRNA leads to weight loss driven by fat loss without loss of muscle mass Body Weight Tissue Weight 0 14 28 0 28 Days Days siRNA siRNA (3 or 10 Sac (3 or 10 DIO DIO Sac mg/kg, SC) Sac mg/kg, SC) 3 mg/kg INHBE-00003 Epididymal white adipose Quadriceps PBS 5 10 mg/kg INHB
Slide 10: INHBE GalNAc-siRNA decreases adipocyte size in MesWAT of DIO mice
INHBE GalNAc-siRNA decreases adipocyte size in MesWAT of DIO mice DIO Lean PBS INHBE-00003 0 28 Days Lean or siRNA Sac DIO (10 mg/kg, SC) Mean Adipocyte Diameter 10 At 23 weeks old (D0), DIO C57Bl6 received a single SC injection of 10mg/kg INHBE-00003 or PBS. Lean mice were sacrificed on D0; INHBE-0
Slide 11: INHBE GalNAc-siRNA augments semaglutide-induced weight loss in DIO mice
INHBE GalNAc-siRNA augments semaglutide-induced weight loss in DIO mice ✓ ~2x greater overall weight loss when added to GLP-1 ✓ Curtails weight regain after the cessation of GLP-1 5 (% of PBS, same time point) 5 % Body weight change Difference in body weight Semaglutide PBS (D0) 0 PBS (daily D0-28)
Slide 12: Preclinical data support potential semi-annual or annual dosing across multiple treatment settings
Preclinical data support potential semi-annual or annual dosing of an INHBE GalNAc-siRNA across multiple treatment settings Monotherapy: provide healthy weight loss with potent loss of fat mass and preservation of muscle mass Add-on to GLP-1s: increase weight loss with GLP-1 therapy or reduce dose
Slide 13: INLIGHT: Phase 1 trial of WVE-007 in adults with overweight or obesity
INLIGHT: Phase 1 trial of WVE-007 in adults living with overweight or obesity, otherwise healthy Randomized, double-blind, placebo-controlled study of ascending doses of investigational WVE-007, a GalNAc-siRNA targeting INHBE mRNA Trial Design SAD Cohort 5 • Objective: Assess dose safety, MAD Cohort
Slide 14: Summary
Summary • Preclinical data show that in DIO mice, Inhbe GalNAc-siRNAs: - lower expression of Inhbe mRNA - reduce body weight - positively impact body composition - double weight loss, when added on to semaglutide - curtail weight regain upon cessation of semaglutide • Preclinical data support potent
Slide 15: Acknowledgements
Acknowledgements • Thanks to all colleagues and contributors from Wave Life Sciences and our collaborators. • Nicole Neuman, Wave Life Sciences, assisted in preparing this presentation. Silencing (RNase H and Ago2) Splicing Editing 15 Selected Wave publications: PMC10201370, PMC9092894, PMID 3525681
Slide 16: Wave Life Sciences - Reimagine possible
LIFE SCIENCES Reimagine possible.
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