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 fourth quarter and full year ended December 31,
2020 and provided a business update.
“Wave is entering 2021 with depth and diversity throughout our
pipeline and platform, the result of focused and deliberate
execution, and a steadfast commitment to leading a new era of RNA
therapeutics. Despite headwinds from the COVID-19 pandemic, we
advanced our pipeline, significantly evolved our platform,
announced our first ADAR editing program and added considerable
talent to our innovative and driven team,” said Paul Bolno, MD,
MBA, President and Chief Executive Officer of Wave Life Sciences.
“We are poised to bring five clinical programs forward in 2021,
including three programs in Huntington’s disease, a fourth program
for ALS and FTD and a fifth program for exon 53 skipping in DMD. We
remain on track to announce data from the Phase 1b/2a PRECISION-HD1
and PRECISION-HD2 trials at the end of the first quarter of 2021
and are excited about adding our next set of clinical programs
incorporating novel PN backbone chemistry modifications, which
preclinically have been shown to increase potency, exposure and
durability in our growing portfolio of investigational stereopure
oligonucleotides. Finally, we strengthened our balance sheet in
September 2020 to support our pipeline and discovery work,
extending our cash runway into the second quarter of 2023 and
ensuring Wave is well-positioned to unlock potential and growth
well beyond 2021.”
2020 Full Year and Recent Business Highlights and
Upcoming Milestones
Three programs with novel PN backbone chemistry
modifications expected to enter clinic in 2021:
- In August 2020, Wave introduced novel PN backbone chemistry
modifications, an advancement from its PRISM™ discovery and
drug development platform. In preclinical studies, these
modifications have been shown to increase potency, exposure and
durability across silencing, splicing and RNA editing
modalities.
- Wave expects to initiate dosing in three clinical trials in
2021, which will assess target engagement, impact on key disease
biomarkers, and initial safety of WVE-003 (targeting SNP3), WVE-004
(targeting C9orf72) and WVE-N531 (targeting exon 53).
- All three compounds were designed with PN backbone chemistry
modifications, and insight from pharmacokinetic (PK) and
pharmacodynamic (PD) studies using in vivo models, as well as
learnings from Wave’s first-generation programs.
Programs for Huntington’s disease (HD): Wave is
developing a unique portfolio of investigational stereopure
oligonucleotides designed to selectively target the mutant allele
of the huntingtin (mHTT) gene, while leaving the wild-type (wtHTT)
protein relatively intact. Wave’s approach to HD is guided by the
recognition that, in addition to a gain of function of the mHTT
protein, people with this disease have lost one copy of the wtHTT
allele, leaving them with a smaller protective reservoir of healthy
protein than unaffected individuals. A growing body of scientific
evidence suggests that preserving as much of this essential protein
as possible is important for favorable health outcomes. Wave’s
allele-selective approach may also enable treatment in the
premanifest setting, before onset of clinical disease.
PRECISION-HD and OLE clinical trials in HD (WVE-120101 and
WVE-120102):
- The PRECISION-HD1 and PRECISION-HD2 Phase 1b/2a trials
evaluating investigational WVE-120101 (SNP1) and WVE-120102 (SNP2),
respectively, in patients with HD are ongoing. WVE-120101 and
WVE-120102 are designed to selectively target the mHTT mRNA
transcript that contains specific single nucleotide polymorphisms
(SNPs).
- Open-label extension (OLE) clinical trials for patients outside
of the U.S. who participated in the Phase 1b/2a PRECISION-HD trials
are also ongoing.
- Wave expects to report biomarker and safety data from all
cohorts of the PRECISION-HD2 trial, along with data from all
completed cohorts up to and including the 16 mg cohort from the
PRECISION-HD1 trial at the end of the first quarter of 2021. Wave
also expects to report data from patients who have received
multiple doses of 8 or 16 mg of WVE-120101 or WVE-120102 in the OLE
trials at the end of the first quarter of 2021.
WVE-003 (SNP3) for HD:
- WVE-003 is Wave’s first allele-selective HD candidate that uses
PN backbone chemistry modifications and was developed using
preclinical in vivo models to enable target engagement assessment
of a specific single nucleotide polymorphism (SNP3). In preclinical
studies, WVE-003 showed selective reduction of mHTT mRNA in vitro,
and potent and durable knockdown of mHTT mRNA in vivo.
- In December 2020, Wave initiated clinical development of
WVE-003 with the submission of a clinical trial application
(CTA).
- Wave expects to initiate dosing in a Phase 1b/2a clinical trial
of WVE-003 for patients with HD in 2021.
Publications:
- In December 2020, in Molecular Therapy Methods & Clinical
Development, Wave published its haplotype phasing method using
single-molecule real-time sequencing and a custom algorithm to
determine bases at SNPs on mutant alleles. Accurate haplotype
phasing of SNPs and the expanded CAG repeat of the huntingtin gene
enables identification of patients with Huntington’s disease
eligible for allele-selective clinical studies.
- In May 2020, Wave’s prospective observational study of the
frequency of SNP1 and SNP2 in patients with HD was published in
Neurology Genetics. The study confirms the feasibility of rapidly
and prospectively identifying SNP1 and/or SNP2 in association with
the mHTT allele in patients with HD, to enable allele-selective,
personalized treatment approaches in eligible patients.
WVE-004 (C9orf72) for amyotrophic lateral sclerosis
(ALS) and frontotemporal dementia (FTD):
- In February 2021, Wave published in Nature Communications
results of initial work to identify and validate its targeting
strategy to achieve variant-selective knockdown of
expansion-containing C9orf72 transcripts with stereopure
oligonucleotides for the treatment of ALS and FTD. The results in
the publication represent the foundational work that led to the
development of Wave’s clinical candidate, WVE-004, which uses PN
backbone chemistry modifications.
- In December 2020, Wave initiated clinical development of
WVE-004 with the submission of a CTA.
- In August 2020, Wave presented preclinical in vivo data for
WVE-004, which demonstrated potent and durable knockdown of more
than 90% of poly GP dipeptide repeat (DPR) protein in the spinal
cord and at least 80% in the cortex, an effect that persisted for
at least six months. Healthy C9orf72 protein was relatively
unchanged over the same time period.
- Wave expects to initiate dosing in a Phase 1b/2a clinical trial
of WVE-004 for both patients with C9-ALS and patients with C9-FTD
in 2021.
WVE-N531 for Duchenne muscular dystrophy (DMD) amenable
to exon 53 skipping:
- WVE-N531 is Wave’s first splicing candidate to incorporate PN
backbone chemistry modifications.
- In a recently completed in vivo study of double knock-out mice
(a model lacking dystrophin and utrophin protein with a severe
phenotype), an oligonucleotide designed with PN backbone chemistry
modifications appeared to significantly increase dystrophin
production and substantially improve survival.
- In a planned clinical trial, Wave will assess dystrophin
production and initial safety in patients with DMD amenable to exon
53 skipping.
- Wave expects to submit a CTA for WVE-N531 by the end of the
first quarter of 2021.
Central nervous system (CNS) programs in collaboration
with Takeda:
- Wave is utilizing PN backbone chemistry modifications to design
stereopure oligonucleotides for CNS indications, including
Alzheimer’s disease, Parkinson’s disease and others, as part of its
ongoing collaboration with Takeda. Wave continues to produce
compelling in vivo data and progress multiple discovery programs
towards portfolio entry and candidate nomination.
- In the fourth quarter of 2020, Wave achieved the first
demonstration of widespread target engagement in the CNS of
non-human primates (NHPs) for the most advanced therapeutic program
in the collaboration. Approximately 90% knockdown of the target
mRNA was observed one month after a single 12 mg intrathecal dose,
and the therapeutic candidate distributed widely across relevant
CNS tissues.
Alpha-1 antitrypsin deficiency (AATD) program with ADAR
editing:
- Wave’s AATD program, its first ADAR editing program, will
target the G-to-A disease-causing mutation in mRNA coded by the
SERPINA1 Z allele. By correcting the single RNA base mutation, ADAR
editing may provide an ideal approach for increasing circulating
levels of wild-type alpha-1 antitrypsin (AAT) protein and reducing
aggregation in the liver, thus simultaneously addressing both the
lung and liver manifestations of the disease.
- In November 2020, Wave presented in vitro data in a primary
hepatocyte SERPINA1 Z allele cell model, which demonstrated that
editing the Z transcript back to wild-type prevents protein
misfolding and increases secretion of edited AAT protein from
hepatocytes.
- Wave expects to deliver in vivo data supporting the continued
development of its AATD program in the first half of 2021.
ADAR editing platform modality:
- Wave’s novel RNA editing modality incorporates PN backbone
chemistry modifications and uses endogenous ADAR (adenosine
deaminases acting on RNA) enzymes via free uptake (non-viral, no
nanoparticles) of A-to-I (G) RNA editing oligonucleotides. ADAR
editing has the potential to unlock many new therapeutic
applications, including restoration, modification or upregulation
of proteins.
Fourth Quarter and Full Year 2020 Financial Results and
Financial GuidanceWave reported a net loss of
$28.8 million in the fourth quarter of 2020 as compared to
$56.8 million in the same period in 2019. The company reported
a net loss of $149.9 million for the year ended December 31,
2020 as compared to $193.6 million for the year ended
December 31, 2019.
Research and development expenses were $30.0 million in the
fourth quarter of 2020 as compared to $49.1 million in the same
period in 2019. Research and development expenses were $130.9
million in 2020, as compared to $175.4 million in 2019. The
decrease in research and development expenses in the fourth quarter
and full year was primarily due to the decrease in external
expenses related to Wave’s decision to discontinue its suvodirsen
program in December 2019, as well as decreases in
compensation-related expenses and other external expenses driven by
Wave's February 2020 cost reduction plan, partially offset by the
increases in external expenses related to Wave’s clinical and
preclinical activities related to its HD programs and its C9orf72
program for ALS and FTD.
General and administrative expenses were $9.7 million in the
fourth quarter of 2020, as compared to $13.8 million in the same
period in 2019. General and administrative expenses were $42.5
million in 2020, as compared to $48.9 million in 2019. The decrease
in general and administrative expenses in the fourth quarter and
full year was primarily driven by the February 2020 cost
reduction plan, which led to decreases in compensation-related
expenses and other external expenses.
Wave ended 2020 with $184.5 million in cash and cash equivalents
as compared to $147.2 million as of December 31, 2019. During 2020,
Wave substantially extended its cash runway, largely by raising
$93.7 million in net proceeds from its September 2020 public
offering and $59.9 million in net proceeds from its at-the-market
equity program.
Wave expects that its existing cash and cash equivalents,
together with expected and committed cash from its existing
collaboration, will enable the company to fund its operating and
capital expenditure requirements into the second quarter of
2023.
Investor Conference Call and WebcastWave
management will host an investor conference call today at 8:00 a.m.
ET to discuss the company’s fourth quarter and full year 2020
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: 6269069. 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 PRISM™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 SciencesWave 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 StatementsThis 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 commencement, patient enrollment, data readouts and
completion of our 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
in vitro and in vivo preclinical data to predict the behavior of
our compounds in humans; our identification of future product
candidates and their therapeutic potential; the anticipated
therapeutic benefits of our potential therapies compared to others;
our ability to design compounds using multiple modalities and the
anticipated benefits of that model; the anticipated benefits of our
proprietary manufacturing processes and our internal manufacturing
capabilities; the potential benefits of PRISM, including our novel
PN backbone chemistry modifications, and our stereopure
oligonucleotides compared with stereorandom oligonucleotides; the
potential benefits of our novel ADAR-mediated RNA editing platform
capabilities compared to others; the benefit of nucleic acid
therapeutics generally; the strength of our intellectual property;
the anticipated duration of our cash runway; and our expectations
regarding the impact of the COVID-19 pandemic on our business.
Actual results may differ materially from those indicated by these
forward-looking statements as a result of various important
factors, including the following: our ability to finance our drug
discovery and development efforts and to raise additional capital
when needed; the ability of our preclinical programs to produce
data sufficient to support our clinical trial applications and the
timing thereof; our ability to maintain the company infrastructure
and personnel needed to achieve our goals; the clinical results of
our programs, which may not support further development of product
candidates; actions of regulatory agencies, which may affect the
initiation, timing and progress of clinical trials; our
effectiveness in managing future clinical trials and regulatory
interactions; the effectiveness of PRISM, including our novel PN
backbone chemistry modifications; the effectiveness of our novel
ADAR-mediated RNA editing platform capability; the continued
development and acceptance of oligonucleotides as a class of
medicines; our ability to demonstrate the therapeutic benefits of
our candidates in clinical trials, including our ability to develop
candidates across multiple therapeutic modalities; our dependence
on third parties, including contract research organizations,
contract manufacturing organizations, collaborators and partners;
our ability to manufacture or contract with third parties to
manufacture drug material to support our programs and growth; our
ability to obtain, maintain and protect our intellectual property;
our ability to enforce our patents against infringers and defend
our patent portfolio against challenges from third parties;
competition from others developing therapies for similar
indications; the severity and duration of the COVID-19 pandemic and
its negative impact on the conduct of, and the timing of
enrollment, completion and reporting with respect to, our clinical
trials; and any other impacts on our business as a result of or
related to the COVID-19 pandemic, as well as the information under
the caption “Risk Factors” contained in our most recent Annual
Report on Form 10-K filed with the Securities and Exchange
Commission (SEC) and in other filings we make with the SEC from
time to time. We undertake no obligation to update the information
contained in this press release to reflect subsequently occurring
events or circumstances.
WAVE LIFE SCIENCES
LTD.UNAUDITED CONSOLIDATED BALANCE
SHEETS(In thousands, except share amounts)
|
|
December 31, 2020 |
|
|
December 31, 2019 |
|
Assets |
|
|
|
|
|
|
|
|
Current assets: |
|
|
|
|
|
|
|
|
Cash and cash equivalents |
|
$ |
184,497 |
|
|
$ |
147,161 |
|
Current portion of accounts receivable |
|
|
30,000 |
|
|
|
20,000 |
|
Prepaid expenses |
|
|
10,434 |
|
|
|
9,626 |
|
Other current assets |
|
|
5,111 |
|
|
|
8,689 |
|
Total current assets |
|
|
230,042 |
|
|
|
185,476 |
|
Long-term assets: |
|
|
|
|
|
|
|
|
Accounts receivable, net of current portion |
|
|
— |
|
|
|
30,000 |
|
Property and equipment, net |
|
|
29,198 |
|
|
|
36,368 |
|
Operating lease right-of-use assets |
|
|
16,232 |
|
|
|
18,101 |
|
Restricted cash |
|
|
3,651 |
|
|
|
3,647 |
|
Other assets |
|
|
115 |
|
|
|
10,658 |
|
Total long-term assets |
|
|
49,196 |
|
|
|
98,774 |
|
Total assets |
|
$ |
279,238 |
|
|
$ |
284,250 |
|
Liabilities, Series A
preferred shares and shareholders’ equity |
|
|
|
|
|
|
|
|
Current liabilities: |
|
|
|
|
|
|
|
|
Accounts payable |
|
$ |
13,795 |
|
|
$ |
9,073 |
|
Accrued expenses and other current liabilities |
|
|
11,971 |
|
|
|
16,185 |
|
Current portion of deferred revenue |
|
|
91,560 |
|
|
|
89,652 |
|
Current portion of operating lease liability |
|
|
3,714 |
|
|
|
3,243 |
|
Total current liabilities |
|
|
121,040 |
|
|
|
118,153 |
|
Long-term liabilities: |
|
|
|
|
|
|
|
|
Deferred revenue, net of current portion |
|
|
41,481 |
|
|
|
63,466 |
|
Operating lease liability, net of current portion |
|
|
25,591 |
|
|
|
29,304 |
|
Other liabilities |
|
|
474 |
|
|
|
1,721 |
|
Total long-term liabilities |
|
|
67,546 |
|
|
|
94,491 |
|
Total liabilities |
|
$ |
188,586 |
|
|
$ |
212,644 |
|
Series A preferred shares, no par
value; 3,901,348 shares issued and outstanding at December 31, 2020
and 2019 |
|
$ |
7,874 |
|
|
$ |
7,874 |
|
Shareholders’ equity: |
|
|
|
|
|
|
|
|
Ordinary shares, no par value; 48,778,678 and 34,340,690 shares
issued and outstanding at December 31, 2020 and 2019,
respectively |
|
|
694,085 |
|
|
|
539,547 |
|
Additional paid-in capital |
|
|
71,573 |
|
|
|
57,277 |
|
Accumulated other comprehensive income |
|
|
389 |
|
|
|
267 |
|
Accumulated deficit |
|
|
(683,269 |
) |
|
|
(533,359 |
) |
Total shareholders’ equity |
|
|
82,778 |
|
|
|
63,732 |
|
Total liabilities, Series A
preferred shares and shareholders’ equity |
|
$ |
279,238 |
|
|
$ |
284,250 |
|
WAVE LIFE SCIENCES
LTD.UNAUDITED CONSOLIDATED STATEMENTS OF
OPERATIONS AND COMPREHENSIVE LOSS(In thousands, except
share and per share amounts)
|
|
Three Months Ended December 31, |
|
|
Twelve Months Ended December 31, |
|
|
|
2020 |
|
|
2019 |
|
|
2020 |
|
|
2019 |
|
Revenue |
|
$ |
9,439 |
|
|
$ |
2,400 |
|
|
$ |
20,077 |
|
|
$ |
15,983 |
|
Operating expenses: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and development |
|
|
30,033 |
|
|
|
49,128 |
|
|
|
130,944 |
|
|
|
175,431 |
|
General and administrative |
|
|
9,719 |
|
|
|
13,805 |
|
|
|
42,510 |
|
|
|
48,869 |
|
Total operating expenses |
|
|
39,752 |
|
|
|
62,933 |
|
|
|
173,454 |
|
|
|
224,300 |
|
Loss from operations |
|
|
(30,313 |
) |
|
|
(60,533 |
) |
|
|
(153,377 |
) |
|
|
(208,317 |
) |
Other income, net: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Dividend income |
|
|
24 |
|
|
|
736 |
|
|
|
584 |
|
|
|
4,912 |
|
Interest income (expense), net |
|
|
— |
|
|
|
4 |
|
|
|
(16 |
) |
|
|
29 |
|
Other income, net |
|
|
659 |
|
|
|
3,023 |
|
|
|
2,058 |
|
|
|
9,738 |
|
Total other income, net |
|
|
683 |
|
|
|
3,763 |
|
|
|
2,626 |
|
|
|
14,679 |
|
Loss before income taxes |
|
|
(29,630 |
) |
|
|
(56,770 |
) |
|
|
(150,751 |
) |
|
|
(193,638 |
) |
Income tax benefit (provision),
net |
|
|
841 |
|
|
|
— |
|
|
|
841 |
|
|
|
— |
|
Net loss |
|
$ |
(28,789 |
) |
|
$ |
(56,770 |
) |
|
$ |
(149,910 |
) |
|
$ |
(193,638 |
) |
Net loss per share attributable
to ordinary shareholders—basic and diluted |
|
$ |
(0.59 |
) |
|
$ |
(1.65 |
) |
|
$ |
(3.82 |
) |
|
$ |
(5.72 |
) |
Weighted-average ordinary shares
used in computing net loss per share attributable to ordinary
shareholders—basic and diluted |
|
|
48,777,001 |
|
|
|
34,303,975 |
|
|
|
39,227,618 |
|
|
|
33,866,487 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Other comprehensive income
(loss): |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net loss |
|
$ |
(28,789 |
) |
|
$ |
(56,770 |
) |
|
$ |
(149,910 |
) |
|
$ |
(193,638 |
) |
Foreign currency translation |
|
|
88 |
|
|
|
(15 |
) |
|
|
122 |
|
|
|
114 |
|
Comprehensive loss |
|
$ |
(28,701 |
) |
|
$ |
(56,785 |
) |
|
$ |
(149,788 |
) |
|
$ |
(193,524 |
) |
Investor Contact:Kate
Rausch617-949-4827krausch@wavelifesci.com
Media Contact:Alicia
Suter617-949-4817asuter@wavelifesci.com
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