Reimagining RNA medicine

First clinical trial of WVE-210201, an exon 51 skipping investigational therapy, in ambulatory and non-ambulatory boys 5 to 18 years old

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov. 6, 2017-- Wave Life Sciences Ltd. (NASDAQ: WVE), a biotechnology company focused on delivering transformational therapies for patients with serious, genetically-defined diseases, today announced the initiation of a global Phase 1 clinical trial for WVE-210201 in Duchenne muscular dystrophy (DMD) patients amenable to exon 51 skipping. This clinical trial marks the next stage in the company’s ongoing commitment to address the significant unmet needs of patients diagnosed with this devastating disease and it is the company’s third clinical trial initiated in 2017.

“The initiation of WVE-210201’s clinical program is an important milestone in potentially delivering meaningful therapies for DMD patients,” said Michael Panzara, MD, MPH, Neurology Franchise Lead of Wave Life Sciences. “We are grateful to the DMD scientific and patient communities with whom we collaborated in designing our clinical program and will continue our close engagement with these key stakeholders as we advance candidates targeting other exons and explore additional innovative approaches to potentially treat DMD.”

The Phase 1 study is a multicenter, double-blind, placebo-controlled clinical trial designed to evaluate the safety, tolerability and plasma concentrations of single ascending doses of WVE-210201 administered intravenously in DMD patients with gene mutations amenable to exon 51 skipping. Data from the Phase 1 trial for WVE-210201 are expected in Q3 2018 and will facilitate the rapid transition to a double-blind, placebo-controlled, multi-dose efficacy study where dystrophin expression and clinical outcomes will be assessed. The clinical program is designed to allow patient participants in the Phase 1 trial to enroll in an open-label extension study in which dosing with WVE-210201 will continue. The open-label extension study and the planned efficacy study are each intended to follow the Phase 1 trial and expected to include an interim efficacy readout of dystrophin expression from muscle biopsies in 2H 2019.

“Wave’s stereopure chemistry platform has enabled the development of WVE-210201 which has shown substantially greater exon 51 skipping efficiency and dystrophin protein restoration in preclinical studies as compared with stereorandom oligonucleotides, including morpholino oligonucleotides,” said Matthew Wood, MD, PhD, Professor of Neuroscience at the University of Oxford and Director of the Oxford Centre for Neuromuscular Disease, Oxford, UK. “These experimental results suggest the potential for meaningful benefits for DMD patients.”

Wave’s first global clinical trial in DMD is expected to enroll up to 40 patients between the ages of 5 and 18 years. The Phase 1 inclusion criteria allow for participation of both ambulatory and non-ambulatory patients, including those previously treated with eteplirsen following an appropriate washout period. The trial has been initiated in the United States, with Europe and other regions to follow. Intravenous doses tested in the Phase 1 trial will escalate through a range expected to be clinically relevant. In the U.S., Wave is required to provide data from ongoing preclinical studies to the FDA in order to progress to the highest dose cohorts and planned multi-dose studies.

“Parent Project Muscular Dystrophy is excited by the progress Wave Life Sciences has made in exon skipping. While advances have been made, there is more to explore within this technology and we appreciate the passion, partnership and understanding the Wave team has shown our Duchenne community. We look forward to continued updates as Wave heads into its Phase 1 clinical trial,” said Pat Furlong, founding President and CEO of Parent Project Muscular Dystrophy.

In addition to its exon 51 program, Wave is leveraging its stereopure chemistry platform to advance investigational therapies targeting additional DMD-related exons. In September 2017, Wave announced that its next DMD development program will target exon 53 and is expected to initiate clinical trials in Q1 2019. In addition, the company is exploring both intravenous and subcutaneous administration for the WVE-210201 and exon 53 programs.

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. Globally, DMD affects approximately one in 3,500 newborn boys.

About WVE-210201

WVE-210201 is an investigational stereopure antisense oligonucleotide that has been shown to induce skipping of exon 51 of dystrophin pre-mRNA in nonclinical studies and is intended for the treatment of Duchenne muscular dystrophy (DMD). Approximately 13% of DMD patients have genetic mutations that are amenable to treatment with exon 51 skipping therapy. Exon-skipping technology has the potential to induce cellular machinery to ‘skip over’ a targeted exon and restore the reading frame, resulting in the production of internally truncated, but functional, dystrophin protein. Wave pre-clinical in vitro experiments using gymnotic delivery (free uptake) of WVE-210201 in DMD patient-derived myoblasts demonstrated efficient exon 51 skipping and dystrophin protein restoration. Preclinical Western blot studies of WVE-210201 demonstrated 52% dystrophin protein restoration as compared with normal skeletal muscle tissue lysates, versus approximately 1% when testing other exon-skipping compounds.

About Wave Life Sciences

Wave Life Sciences is a biotechnology company focused on delivering transformational therapies for patients with serious, genetically-defined diseases. Our chemistry platform enables the creation of highly specific, well characterized oligonucleotides designed to deliver superior efficacy and safety across multiple therapeutic modalities. Our pipeline is initially focused on neurological disorders and extends across several other therapeutic areas.

Forward Looking Information

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the initiation of Wave’s first clinical trial for WVE-210201 for Duchenne muscular dystrophy patients with gene mutations amenable to exon 51 skipping, including Wave’s ability to screen and enroll patients; Wave’s ability to implement its global clinical development plan for WVE-210201; the potential benefits of Wave’s exon-skipping approach; the potential benefits of the global clinical development plan and design of the Phase 1 trial; Wave’s expectations regarding dose escalation; and Wave’s strategy and business plans. 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 Wave 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, including, without limitation, uncertainties inherent in research and drug development, interactions with global regulatory authorities, future clinical data and analysis, the decisions of global regulatory authorities as to whether and when to approve any application that may be filed for any of our candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, our ability to benefit from external growth opportunities and/or obtain regulatory clearances, risks associated with intellectual property, volatile economic conditions, healthcare reform, as well as those discussed or identified in Wave’s public filings with the SEC. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Wave’s Annual Report on Form 10-K for the year ended December 31, 2016, as filed with the Securities and Exchange Commission (SEC) on March 16, 2017, and in other filings that Wave makes with the SEC from time to time. Any forward-looking statements contained in this press release represent Wave’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Wave explicitly disclaims any obligation to update any forward-looking statements.

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Source: Wave Life Sciences Ltd.

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