Full Press Release Details
Wave Life Sciences Provides Positive Update on Proof-of-Concept Study for WVE-N531 in Duchenne Muscular Dystrophy
53% mean exon skipping and <1% (BLQ) mean dystrophin expression six weeks after initiating biweekly multidosing
PN chemistry improved pharmacology of WVE-N531 compared with Wave s first-generation DMD
program demonstrated high muscle concentrations with a mean of 42 micrograms/gram
WVE-N531 appeared safe and well tolerated
Third Wave clinical trial evaluating a PN chemistry-containing compound to achieve target engagement in 2022
Wave to host investor conference call and webcast at 8:30 a.m. ET today
CAMBRIDGE, Mass., December 19, 2022 Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage genetic medicines company
committed to delivering life-changing treatments for people battling devastating diseases, announced today a positive update from the initial cohort of the Phase 1b/2a
proof-of-concept study of WVE-N531 in three boys with Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping. High muscle
concentrations of WVE-N531 and exon skipping were observed six weeks after initiating biweekly multidosing at 10 mg/kg, achieving
proof-of-concept in the study. WVE-N531 also appeared safe and well-tolerated.
These data provide early evidence that WVE-N531 is working as intended, leading to substantial exon skipping
after just three consecutive doses. This is the earliest timepoint at which exon skipping has been reported in a clinical trial of boys with DMD, said Anne-Marie Li-Kwai-Cheung, Chief Development Officer of Wave Life Sciences. While
dystrophin was below the lower limit of detection, it is expected that dystrophin protein production would lag splicing of the RNA transcript. We are encouraged by these early results and are evaluating next steps for the program, including the
continuation of this initial cohort. We would like to express our sincerest gratitude to the boys, their families, and the investigators who participated in the study.
There remains a significant unmet need in DMD for new treatment options. It is exciting to see this level of exon skipping in a short period of time,
especially since skipping would be expected to increase over a longer dosing interval, said Laurent Servais, MD, PhD, professor of pediatric neuromuscular diseases at the MDUK Oxford Neuromuscular Center and primary investigator in the WVE-N531 study. Based on the data, it appears Wave s next-generation chemistry has led to significantly improved pharmacology. Expression of dystrophin after longer exposure will, of course, be key to
confirm the promise of these early data. I look forward to the continued progression of clinical research for WVE-N531.
Three ambulatory boys participated in this open-label, intra-patient dose escalation clinical trial (NCT04906460). The boys received single escalating
doses of 1, 3, 6 and 10 mg/kg; and in the multidose portion of the study, the same boys received three doses of 10 mg/kg every other week. A muscle biopsy was taken two weeks after the third and final dose (six weeks after the first dose).
These data indicate PN chemistry can improve potency, distribution and durability of splicing oligonucleotides without needing peptide or antibody
conjugates, clearly demonstrating the increasing potential of Wave s PRISM platform, said Paul Bolno, MD, MBA, President and Chief Executive Officer of Wave Life Sciences. This is Wave s third clinical trial in 2022 to
demonstrate the impact of PN chemistry, as well as our third clinical trial to demonstrate translation of preclinical data in humans. In 2023, we are looking forward to determining next steps for WVE-N531,
advancing our silencing clinical programs, and bringing a whole new modality into the clinic with our RNA editing and upregulation capability.
Investor Conference Call and Webcast
will host an investor conference call today at 8:30 a.m. ET to discuss results from this WVE-N531 proof-of-concept study. The
webcast of the conference call and corresponding slide presentation may be accessed by visiting Events on the investor relations section of the Wave Life Sciences corporate website: ir.wavelifesciences.com/events-and-presentations.
Analysts planning to participate during the Q&A
portion of the live call can join the conference call at the audio conferencing link available here. Once registered, participants will receive the dial-in information. Following the live event, an
archived version of the webcast will be available on the Wave Life Sciences website.
About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic neuromuscular disorder caused predominantly by out-of-frame deletions in the dystrophin gene, resulting in absent or defective dystrophin protein. Dystrophin protein is needed for normal muscle maintenance and operation.
Because of the genetic mutations in DMD, the body cannot produce functional dystrophin, which results in progressive and irreversible loss of muscle function, including the heart and lungs. Worldwide, DMD affects approximately one in 5,000 newborn
boys. Approximately 8%-10% of boys with DMD have mutations amenable to treatment with an exon 53 skipping therapy. Exon skipping aims to address the underlying cause of DMD by promoting the production of
dystrophin protein to stabilize or slow disease progression.
PRISM is Wave Life Sciences proprietary discovery and drug development platform that enables genetically defined diseases to be targeted with stereopure
oligonucleotides across multiple therapeutic modalities, including silencing, splicing and editing. PRISM combines the company s unique ability to construct stereopure oligonucleotides with a deep understanding of how the interplay among
oligonucleotide sequence, chemistry and backbone stereochemistry impacts key pharmacological properties. By exploring these interactions through iterative analysis of in vitro and in vivo outcomes and machine learning-driven predictive
modeling, the company continues to define design principles that are deployed across programs to rapidly develop and manufacture clinical candidates that meet pre-defined product profiles.
About Wave Life Sciences
Wave Life Sciences (Nasdaq: WVE) is a clinical-stage genetic medicines company committed to delivering life-changing treatments for people battling devastating
diseases. Wave aspires to develop best-in-class medicines across multiple therapeutic modalities using PRISM, the company s proprietary discovery and drug
development platform that enables the precise design, optimization, and production of stereopure oligonucleotides. Driven by a resolute sense of urgency, the Wave team is targeting a broad range of genetically defined diseases so that patients and
families may realize a brighter future. To find out more, please visit www.wavelifesciences.com and follow Wave on Twitter @WaveLifeSci.
Forward-Looking Statements
This press release contains
forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, our understanding of the anticipated therapeutic benefit of
WVE-N531 as a therapy for DMD; our understanding of the cause of DMD and the potential addressable patients amenable to treatment with an exon 53 skipping therapy; our expectations that the level of exon
skipping would be expected to increase over a longer dosing interval; our expectation that dystrophin protein production would lag splicing of the RNA transcript; our beliefs regarding the learnings gained from our first-generation DMD program; our
expectation regarding the continued progression of clinical research for WVE-N531; and the potential benefits of PRISM, including our novel PN backbone chemistry modifications, and our stereopure
oligonucleotides compared with stereorandom oligonucleotides. The words may, will, could, would, should, expect, plan, anticipate, intend,
believe, estimate, predict, project, potential, continue, target and similar expressions are intended to identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management s current expectations and beliefs and are subject to a number of risks, uncertainties and important
factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release and actual results may differ materially from those indicated by these
forward-looking statements as a result of these risks, uncertainties and important factors, including, without limitation, the risks and uncertainties described in the section entitled Risk Factors in Wave s most recent Annual
Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as amended, and in other filings Wave makes with the SEC from time to time. Wave undertakes no obligation to update the information
contained in this press release to reflect subsequently occurring events or circumstances.