Wave Life Sciences Announces Submission of First Clinical Trial Application for WVE-007 (siRNA Targeting INHBE) in Obesity

Wave Life Sciences Ltd. recently announced the submission of its first clinical trial application (CTA) for WVE-007 in obesity. WVE-007 is an investigational GalNAc-conjugated small interfering RNA (siRNA) designed to silence Inhibin βE (INHBE) gene expression, which would induce fat burning (lipolysis) to decrease body weight without impacting muscle mass. Wave expects CTA approval and initiation of the first-in-human study of WVE-007 in the first quarter of 2025.

“Our WVE-007 program, which uses Wave’s best-in-class GalNAc-siRNA capabilities with proprietary chemistry, has potential to be dosed once or twice annually and may ultimately be used across the obesity treatment continuum for sustainable weight loss and cardiometabolic risk reduction,” said Paul Bolno, MD, MBA, President and Chief Executive Officer at Wave Life Sciences. “With a growing understanding of human genetics and opportunities to directly impact adipose tissue, INHBE has emerged as an exciting, novel therapeutic target to address obesity, without the challenges of current standard-of-care therapeutics.”

Human genetics provide strong evidence for INHBE as a therapeutic target. Individuals who have a protective loss-of-function mutation in the INHBE gene have a healthier cardiometabolic profile, including less abdominal fat, lower triglycerides, and lower risk of type 2 diabetes and cardiovascular disease. WVE-007 is designed to induce this healthy phenotype through INHBE gene silencing, leading to fat burning and improvements in metabolic health. In preclinical studies using a mouse model of diet induced obesity (DIO), a single dose of Wave’s INHBE siRNA led to weight loss on par with semaglutide, with no muscle loss. When administered as an add-on to semaglutide, a single dose doubled the amount of weight loss. In another study, Wave’s INHBE siRNA also prevented weight regain when semaglutide treatment was discontinued.

Wave’s first-in-human study of WVE-007 is a Phase 1 clinical trial in adults living with overweight or obesity. The trial is designed to assess safety, tolerability, pharmacokinetics, and biomarkers for target engagement, as well as body composition and metabolic health.

Wave Life Sciences (Nasdaq: WVE) is a biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health. Wave’s RNA medicines platform, PRISM, combines multiple modalities, chemistry innovation and deep insights in human genetics to deliver scientific breakthroughs that treat both rare and prevalent disorders. Its toolkit of RNA-targeting modalities includes editing, splicing, RNA interference and antisense silencing, providing Wave with unmatched capabilities for designing and sustainably delivering candidates that optimally address disease biology. Wave’s diversified pipeline includes clinical programs in Duchenne muscular dystrophy, Alpha-1 antitrypsin deficiency and Huntington’s disease, as well as a preclinical program in obesity. Driven by the calling to “Reimagine Possible”, Wave is leading the charge toward a world in which human potential is no longer hindered by the burden of disease. Wave is headquartered in Cambridge, MA. For more information on Wave’s science, pipeline and people, please visit www.wavelifesciences.com and follow Wave on X (formerly Twitter) and LinkedIn.