Wave Life Sciences Reports First Quarter 2022 Financial Results and Provides Business Update Delivered first clinical data demonstrating target engagement and translation of PN chemistry s impact in clinic; Adapting ongo

Wave Life Sciences Reports First Quarter 2022 Financial Results and Provides Business Update

Delivered first clinical data demonstrating target engagement and translation of PN chemistry s impact in clinic;

Adapting ongoing Phase 1b/2a FOCUS-C9 clinical trial to optimize dose level and frequency, with

additional single and

multidose data expected throughout 2022

Clinical data also expected in 2022 from Huntington s disease (WVE-003) and Duchenne muscular

dystrophy (WVE-N531)

Robust preclinical datasets for first-in-class AATD program

demonstrate restoration of levels of AAT relevant for

potential lung protection and reduction of liver-damaging aggregates with

GalNAc AIMers; IND enabling toxicology

studies for lead AATD candidate on-track to initiate

Wave to host investor conference call and webcast at 8:30 a.m. ET today

CAMBRIDGE, Mass., May 12, 2022 Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage genetic medicines company committed to

delivering life-changing treatments for people battling devastating diseases, today announced financial results for the first quarter ended March 31, 2022 and provided a business update.

Thus far in 2022, Wave has achieved several important milestones, with the highlight being our first clinical data demonstrating successful target

engagement with WVE-004 in the ongoing FOCUS-C9 clinical trial for C9-ALS and C9-FTD. We

observed potent and durable reductions of the poly(GP) biomarker with low single doses of WVE-004, demonstrating that our preclinical data for PN-containing

oligonucleotides are beginning to translate in the clinic, said Paul Bolno, MD, MBA, President and Chief Executive Officer of Wave Life Sciences. These initial results are compelling and reinforce the potential of our unique

oligonucleotide platform and our expectation to see the advantages of PN chemistry manifest in our other pipeline programs. We also continue to rapidly advance our WVE-003 program for HD and WVE-N531 program for DMD towards initial data updates later this year. We are also pleased with the recognition we are receiving with our endogenous RNA editing modality, which is being highlighted through

scientific presentations and our recent Nature Biotechnology publication. Alpha-1 antitrypsin deficiency (AATD) is uniquely suited for an RNA editing therapeutic, and our AATD program is rapidly advancing

towards clinical development with IND enabling studies on track to initiate in the third quarter of this year.

Recent Pipeline and Business

Announced first clinical data from ongoing FOCUS-C9 trial of

WVE-004 for C9-ALS and C9-FTD demonstrating potent and durable target engagement with low, single doses

Continued to advance clinical trials evaluating

WVE-003 targeting SNP3 for Huntington s disease (HD) and WVE-N531 for Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping

Presented preclinical AIMer data for AATD program supporting the potential for a novel,

first-in-class, subcutaneous therapeutic to address both lung and liver manifestations of disease

Scientific publications highlight breadth and potential of Wave s therapeutic oligonucleotide platform, including novel

PN-chemistry and RNA editing modality

Key Anticipated 2022 Milestones

WVE-004 for C9-ALS and C9-FTD:

GalNAc-conjugated program for AATD:

First Quarter 2022 Financial

Results and Financial Guidance

Wave reported a net loss of $37.8 million in the first quarter of 2022, as compared

to $42.5 million in the same period in 2021.

Wave recorded revenue of $1.8 million for the first quarter of 2022, primarily under the

Takeda Collaboration. Wave did not record any revenue under the Takeda Collaboration in the first quarter of 2021.

Research and development expenses

were $27.5 million in the first quarter of 2022 as compared to $33.4 million in the same period in 2021. The decrease in research and development expenses in the first quarter was primarily due to decreased external expenses

related to our previously disclosed discontinued PRECISION-HD programs, partially offset by increased internal and external expenses related to PRISM, including ADAR editing, and other ongoing programs.

General and administrative expenses were $12.4 million in the first quarter of 2022 as compared to $10.1 million in the same period in

2021. The increase in general and administrative expenses in the first quarter of 2022 was primarily due to increases in compensation-related expenses, as well as increases in professional services expenses and other general and administrative

As of March 31, 2022, Wave had $111.7 million in cash, cash equivalents and short-term investments. As of

December 31, 2021, Wave had $150.6 million in cash and cash equivalents. This decrease was mainly due to Wave s year-to-date net loss of

Wave expects that its existing cash, cash equivalents and short-term investments will enable the company to fund its operating and

capital expenditure requirements into the second quarter of 2023.

Investor Conference Call and Webcast

Wave management will host an investor conference call today at 8:30 a.m. ET to discuss the company s first quarter 2022 financial results and provide a

business update. The conference call may be accessed by dialing (866) 220-8068 (domestic) or (470) 495-9153 (international) and entering conference ID: 092347. The live

webcast may be accessed from the Investor Relations section of the Wave Life Sciences corporate website at ir.wavelifesciences.com. Following the webcast, a replay will be available on the website.

About the FOCUS-C9 Clinical Trial

The FOCUS-C9 trial is an ongoing, global, multicenter, randomized, double-blind, placebo-controlled Phase 1b/2a

clinical trial to assess the safety and tolerability of single- and multiple-ascending intrathecal doses of WVE-004 for people with C9-ALS and/or C9-FTD. Additional objectives include measurement of poly(GP) DPR proteins in the cerebrospinal fluid (CSF), plasma and CSF pharmacokinetics (PK), and exploratory biomarkers and clinical outcomes. The FOCUS-C9 trial is designed to be adaptive, with dose escalation and dosing frequency being guided by an independent committee.

In an initial data analysis, reductions in poly(GP) were observed across all active treatment groups (10 mg,

n=2 patients; 30 mg, n=4 patients; 60 mg, n=3 patients), reaching statistical significance versus placebo (n=3 patients) after single 30 mg doses, with a 34% reduction in poly(GP) at day 85 (p=0.011). At the time of analysis, none of the patients

dosed with 60 mg had reached day 85. As the poly(GP) reduction in the 30 mg single dose cohort does not appear to have plateaued, Wave will extend the observation period from approximately three months (85 days) to approximately six months to

identify the maximum reduction of poly(GP) and duration of effect of low single doses. Based on the durability and potency observed in the 30 mg cohort, FOCUS-C9 has been adapted to include additional patients

receiving 20 mg and 30 mg single doses of WVE-004. Adverse events (AEs) were balanced across treatment groups, including placebo, and were mostly mild to moderate in intensity. Four patients (including one on

placebo) experienced severe and/or serious adverse events; three were reported by the investigators to be related to ALS or administration, and one was reported by the investigator to be related to study drug. There were no treatment-associated

elevations in CSF white blood cell counts or protein and no other notable laboratory abnormalities were observed.

Support for FOCUS-C9 is provided by the Alzheimer s Drug Discovery Foundation.

About Amyotrophic Lateral Sclerosis and

Frontotemporal Dementia

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which the progressive degeneration of motor

neurons in the brain and spinal cord leads to the inability to initiate or control muscle movement. People with ALS may lose the ability to speak, eat, move and breathe. ALS affects as many as 20,000 people in the United States.

Frontotemporal dementia (FTD) is a fatal neurodegenerative disease in which progressive nerve cell loss in the brain s frontal lobes and temporal lobes

leads to personality and behavioral changes, as well as the gradual impairment of language skills. It is the second most common form of early-onset dementia after Alzheimer s disease in people under the age of 65. FTD affects as many as 70,000

people in the United States.

A hexanucleotide repeat expansion (G4C2) is the most common known genetic cause of the sporadic and inherited forms of ALS

and FTD. The expansion leads to production of modified sense and antisense transcripts that can form nuclear RNA foci and encode dipeptide protein repeats (DPRs), which are believed to drive disease pathology. Additionally, the G4C2 expansion can

decrease expression of C9orf72 protein, affecting regulation of neuronal function and the immune system.

In the United States, mutations of the C9orf72

gene are present in approximately 40% of familial ALS cases and ~8-10% of sporadic ALS cases. In FTD, the mutations appear in 38% of familial cases and 6% of sporadic cases.

About Huntington s Disease

disease (HD) is a debilitating and ultimately fatal autosomal dominant neurological disorder, characterized by cognitive decline, psychiatric illness, and chorea. HD causes nerve cells in the brain to deteriorate over time, affecting thinking

ability, emotions, and movement. HD is caused by an expanded cytosine-adenine-guanine (CAG) triplet repeat in the huntingtin (HTT) gene that results in production of mutant HTT (mHTT) protein. Accumulation of mHTT causes progressive loss of neurons

in the brain. Wild-type, or healthy, HTT (wtHTT) protein is critical for neuronal function and suppression may have detrimental long-term consequences. Approximately 30,000 people in the United States have symptomatic HD and more than 200,000 others

are at risk for developing the disease. There are currently no approved disease-modifying therapies available.

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 DMD patients 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

About Wave Life Sciences

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 concerning our goals, beliefs, expectations, strategies, objectives and plans, and other statements that

are not necessarily based on historical facts, including statements regarding the following, among others: the anticipated initiation, site activation, patient recruitment, patient enrollment, dosing, generation of data and completion of our

adaptive clinical trials, and the announcement of such events; the protocol, design and endpoints of our ongoing and planned clinical trials; the future performance and results of our programs in clinical trials; future preclinical activities and

programs; regulatory submissions; the progress and potential benefits of our collaborations with partners; the potential of our preclinical data to predict the behavior of our compounds in humans; our identification and expected timing of future