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 second quarter ended June 30, 2021 and provided a
business update.
“Since the start of the second quarter, Wave has achieved two
significant milestones: the intrathecal dosing of patients with an
oligonucleotide containing PN chemistry and preclinical
proof-of-concept protein restoration in vivo with ADAR editing for
our alpha-1 antitrypsin deficiency program. Both accomplishments
reflect the significant evolution of our PRISM platform since
Wave’s founding,” said Paul Bolno, MD, MBA, President and Chief
Executive Officer of Wave Life Sciences. “Amyotrophic lateral
sclerosis and frontotemporal dementia are both areas of high unmet
need; therefore we are excited to advance WVE-004 in the FOCUS-C9
clinical trial, which is open to both patient populations as they
have the same genetic cause of disease. Additionally, we continue
to progress our clinical trials for Huntington’s disease and
Duchenne muscular dystrophy. Our novel PN chemistry, stereochemical
control and years of platform learnings have enabled us to lead the
field on RNA editing and develop a best-in-class modality using
endogenous ADAR enzymes, which further expands our genetic
medicines toolkit. In June we delivered our first preclinical
proof-of-concept data for our AATD program, and we believe RNA
editing is the ideal approach to address this disease. Our upcoming
Analyst and Investor Research Day in September will feature new
data on our ADAR editing capability, AATD program, and updates on
applications of ADAR editing beyond liver, including in the
CNS.”
Highlights and upcoming milestones for clinical
silencing and exon skipping programs:
WVE-004 for C9orf72-associated amyotrophic lateral
sclerosis (ALS) and frontotemporal dementia (FTD):
- WVE-004 is an investigational stereopure antisense
oligonucleotide designed to selectively target transcript variants
containing a hexanucleotide repeat expansion (G4C2) associated with
the C9orf72 gene, which is one of the most common genetic causes of
the sporadic and inherited forms of ALS and FTD. WVE-004 uses
Wave’s novel PN backbone chemistry modifications (PN
chemistry).
Clinical trial update:
- In July 2021, Wave announced the initiation of dosing in the
Phase 1b/2a FOCUS-C9 clinical trial of WVE-004 in
C9orf72-associated ALS and FTD.
- The FOCUS-C9 trial is adaptive, with dose escalation and dosing
frequency being guided by an independent committee.
- Wave expects to generate clinical data through 2022 to provide
insight into the clinical effects of PN chemistry and enable
decision making for WVE-004.
Presentations and preclinical data:
- In the second quarter, Wave highlighted preclinical in vivo
data for WVE-004 at multiple scientific meetings:
- American Academy of Neurology (AAN) 2021 Virtual Annual Meeting
in April 2021
- European Network to Cure ALS (ENCALS) in May 2021
- Keystone eSymposia: Neurodegenerative Diseases: Genes,
Mechanisms and Therapeutics in June 2021
- The preclinical in vivo data for WVE-004 demonstrated potent
knockdown of more than 90% of polyGP dipeptide repeat (DPR)
proteins in the spinal cord and at least 80% in the cortex of a
transgenic mouse model, which was durable out to at least six
months. C9orf72 protein was relatively unchanged over the same time
period.
- At Keystone eSymposia, Wave also shared preclinical data
demonstrating the impact of applying PN chemistry to WVE-004, which
resulted in improved activity and durability in vivo in both spinal
cord and cortex compared with a control molecule of the same
sequence designed without PN chemistry.
WVE-003 targeting SNP3 for Huntington’s disease
(HD):
- WVE-003 is Wave’s next-generation stereopure HD candidate and
first HD candidate to use PN chemistry and leverage transgenic
models to assess target engagement in vivo.
- WVE-003 is designed to selectively target the mutant allele of
the huntingtin (mHTT) gene, while leaving the wild-type (healthy)
HTT (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 less wtHTT
protein, leaving them with a smaller protective reservoir of
healthy protein compared to unaffected individuals. A growing body
of scientific evidence suggests that preserving as much of this
essential protein as possible, when in the setting of stress from
toxic mHTT protein, may be important for favorable clinical
outcomes.
- Preclinical data for WVE-003 demonstrated selective reduction
of mHTT mRNA in vitro and potent and durable knockdown of mHTT mRNA
in vivo.
- Sites are activated and recruitment is underway in the
SELECT-HD Phase 1b/2a clinical trial of WVE-003 in patients with
early manifest HD, and Wave expects to initiate dosing in 2021.
SELECT-HD is adaptive, with dose escalation and dosing frequency to
be guided by an independent committee.
WVE-N531 for Duchenne muscular dystrophy (DMD) amenable
to exon 53 skipping:
- WVE-N531 is Wave’s first stereopure splicing candidate to
incorporate PN chemistry, which Wave advanced following results of
an in vivo study in double knock-out mice (dKO) that showed an
oligonucleotide designed with PN chemistry appeared to
significantly increase dystrophin production and substantially
improve survival, compared to oligonucleotides designed with Wave’s
first-generation chemistry.
- Sites are activated and recruitment is underway in a clinical
trial of WVE-N531 in patients with DMD amenable to exon 53
skipping. Wave expects to initiate dosing in 2021.
ADAR editing preclinical program progress and upcoming
milestones:
ADAR editing (RNA editing using endogenous ADAR enzymes)
capability:
- Wave’s leading RNA editing capability leverages widely
expressed endogenous ADAR enzymes to achieve highly specific A-to-I
(G) RNA editing in vivo using stereopure oligonucleotides, without
the need for lipid nanoparticles (LNPs) or AAV vectors and without
altering DNA.
- In May 2021, at the 24th Annual Meeting of the American Society
of Gene and Cell Therapy (ASGCT), Wave presented its novel ADAR
editing capability, which leverages PN chemistry. This presentation
highlighted proof-of-concept data demonstrating potent and durable
editing of ACTB in vivo in the liver of non-human primates (NHPs)
of up to 50% using GalNAc-conjugated oligonucleotides, as well as
potent editing of ACTB in vivo in multiple tissues of NHPs using
non-conjugated oligonucleotides. The presentation also included
data demonstrating potent editing in vivo in the CNS with Wave’s
proprietary humanized ADAR transgenic mouse model.
- Wave continues to evaluate ADAR editing oligonucleotides for
different disease targets, including neurology targets, leveraging
its proprietary mouse model.
- Wave expects to present additional ADAR editing data at its
upcoming Analyst and Investor Research Day on September 28, 2021,
and at scientific congresses in 2021.
Alpha-1 antitrypsin deficiency (AATD) program with ADAR
editing:
- Wave’s AATD program, its first therapeutic ADAR editing
program, uses stereopure oligonucleotides to correct the single
base mutation in mRNA coded by the SERPINA1 Z allele. ADAR editing
may provide an ideal approach to addressing AATD by increasing
circulating levels of healthy alpha-1 antitrypsin (M-AAT) protein
and reducing aggregation in the liver, thus simultaneously
addressing both the lung and liver manifestations of the
disease.
- In June 2021, Wave presented proof-of-concept preclinical in
vivo data that demonstrated up to 40% editing of human SERPINA1 Z
allele mRNA in the liver at an initial timepoint, which resulted in
a therapeutically meaningful increase in circulating, functional
wild-type AAT protein. This initial in vivo study utilized Wave’s
proprietary transgenic mouse model, which has both the human
SERPINA1 Z-allele as well as human ADAR that is expressed
comparably to human cells. These data have been accepted for an
oral presentation at the 17th Annual Meeting of the Oligonucleotide
Therapeutics Society (OTS) being held September 26 – 29, 2021.
- Wave’s preclinical studies for its AATD program are ongoing and
additional data on durability and dose response are expected in the
second half of 2021.
Preclinical CNS programs in collaboration with
Takeda:
Multiple programs (including WVE-005) for central
nervous system (CNS) indications:
- Wave is utilizing PN chemistry 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, including target engagement in the CNS of non-human
primates, and progress multiple discovery programs towards
portfolio entry and candidate nomination.
Upcoming events:
Analyst and Investor Research Day to be held September
28, 2021:
- Wave announced today it will hold an Analyst and Investor
Research Day on Tuesday, September 28th, at 10:00 a.m. ET to
discuss its PRISMTM platform, share new preclinical data from its
neurology programs and proof-of-concept data for its ADAR editing
capability, and provide an update on its first ADAR editing program
for AATD.
Second Quarter 2021 Financial Results and Financial
Guidance
Wave reported a net loss of $38.8 million in the second
quarter of 2021 as compared to $40.5 million in the same
period in 2020.
Research and development expenses were $31.6 million in the
second quarter of 2021 as compared to $31.5 million in the
same period in 2020. While the total research and development
expenses remained relatively consistent year-over-year, there were
changes in how the expenses were distributed between programs.
There were increased external expenses related to Wave’s C9orf72
program and other discovery and development programs, including
PRISM, and Wave’s reimbursed research and preclinical expenses
related to its Takeda collaboration. These increases were almost
entirely offset by decreased external expenses related to Wave’s
discontinued clinical programs.
General and administrative expenses were $11.0 million in
the second quarter of 2020 as compared to $10.2 million in the
same period in 2020. The increase in general and administrative
expenses in the second quarter of 2021 was mainly driven by
increased external general and administrative expenses, as well as
increased compensation-related expenses.
As of June 30, 2021, Wave had $143.8 million in cash
and cash equivalents as compared to $184.5 million as of
December 31, 2020. The decrease in cash and cash equivalents
was mainly due to Wave’s year-to-date net loss of
$81.2 million, partially offset by the receipt of
$30.0 million in research support funding from Takeda under
the company’s collaboration in the second quarter and
$13.1 million in year-to-date net proceeds under
Wave’s 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 8:30 a.m.
ET to discuss the company’s second quarter and 2021 financial
results and provide a business update. The conference call may be
accessed by dialing (800) 708-4540 (domestic) or (847) 619-6397
(international) and entering conference ID: 50197439. 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 initiation, site activation, patient recruitment,
patient enrollment, dosing, data readouts 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 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, including their
receptiveness to our adaptive trial designs; 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)
|
|
June 30, 2021 |
|
|
December 31, 2020 |
|
Assets |
|
|
|
|
|
|
|
|
Current assets: |
|
|
|
|
|
|
|
|
Cash and cash equivalents |
|
$ |
143,840 |
|
|
$ |
184,497 |
|
Current portion of accounts receivable |
|
|
— |
|
|
|
30,000 |
|
Prepaid expenses |
|
|
9,188 |
|
|
|
10,434 |
|
Other current assets |
|
|
6,403 |
|
|
|
5,111 |
|
Total current assets |
|
|
159,431 |
|
|
|
230,042 |
|
Long-term assets: |
|
|
|
|
|
|
|
|
Property and equipment, net |
|
|
25,842 |
|
|
|
29,198 |
|
Operating lease right-of-use assets |
|
|
15,189 |
|
|
|
16,232 |
|
Restricted cash |
|
|
3,651 |
|
|
|
3,651 |
|
Other assets |
|
|
2,298 |
|
|
|
115 |
|
Total long-term assets |
|
|
46,980 |
|
|
|
49,196 |
|
Total assets |
|
$ |
206,411 |
|
|
$ |
279,238 |
|
Liabilities, Series A
preferred shares and shareholders’ equity |
|
|
|
|
|
|
|
|
Current liabilities: |
|
|
|
|
|
|
|
|
Accounts payable |
|
$ |
8,655 |
|
|
$ |
13,795 |
|
Accrued expenses and other current liabilities |
|
|
9,923 |
|
|
|
11,971 |
|
Current portion of deferred revenue |
|
|
24,177 |
|
|
|
91,560 |
|
Current portion of operating lease liability |
|
|
3,966 |
|
|
|
3,714 |
|
Total current liabilities |
|
|
46,721 |
|
|
|
121,040 |
|
Long-term liabilities: |
|
|
|
|
|
|
|
|
Deferred revenue, net of current portion |
|
|
106,088 |
|
|
|
41,481 |
|
Operating lease liability, net of current portion |
|
|
23,547 |
|
|
|
25,591 |
|
Other liabilities |
|
|
339 |
|
|
|
474 |
|
Total long-term liabilities |
|
$ |
129,974 |
|
|
$ |
67,546 |
|
Total liabilities |
|
$ |
176,695 |
|
|
$ |
188,586 |
|
Series A preferred shares, no par
value; 3,901,348 shares issued and outstanding at June 30, 2021 and
December 31, 2020 |
|
$ |
7,874 |
|
|
$ |
7,874 |
|
Shareholders’ equity: |
|
|
|
|
|
|
|
|
Ordinary shares, no par value; 50,576,466 and 48,778,678 shares
issued and outstanding at June 30, 2021 and December 31, 2020,
respectively |
|
$ |
707,714 |
|
|
$ |
694,085 |
|
Additional paid-in capital |
|
|
78,358 |
|
|
|
71,573 |
|
Accumulated other comprehensive income |
|
|
269 |
|
|
|
389 |
|
Accumulated deficit |
|
|
(764,499 |
) |
|
|
(683,269 |
) |
Total shareholders’ equity |
|
$ |
21,842 |
|
|
$ |
82,778 |
|
Total liabilities, Series A
preferred shares and shareholders’ equity |
|
$ |
206,411 |
|
|
$ |
279,238 |
|
WAVE LIFE SCIENCES
LTD.UNAUDITED CONSOLIDATED STATEMENTS OF
OPERATIONS AND COMPREHENSIVE LOSS
(In thousands, except share and per share
amounts)
|
|
Three Months Ended June 30, |
|
|
Six Months Ended June 30, |
|
|
|
2021 |
|
|
2020 |
|
|
2021 |
|
|
2020 |
|
Revenue |
|
$ |
2,776 |
|
|
$ |
3,027 |
|
|
$ |
2,776 |
|
|
$ |
7,188 |
|
Operating expenses: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and development |
|
|
31,635 |
|
|
|
31,478 |
|
|
|
65,028 |
|
|
|
72,636 |
|
General and administrative |
|
|
10,969 |
|
|
|
10,205 |
|
|
|
21,047 |
|
|
|
23,201 |
|
Total operating expenses |
|
|
42,604 |
|
|
|
41,683 |
|
|
|
86,075 |
|
|
|
95,837 |
|
Loss from operations |
|
|
(39,828 |
) |
|
|
(38,656 |
) |
|
|
(83,299 |
) |
|
|
(88,649 |
) |
Other income (expense), net: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Dividend income and interest income, net |
|
|
8 |
|
|
|
133 |
|
|
|
19 |
|
|
|
521 |
|
Other income (expense), net |
|
|
1,054 |
|
|
|
(2,005 |
) |
|
|
2,050 |
|
|
|
107 |
|
Total other income (expense),
net |
|
|
1,062 |
|
|
|
(1,872 |
) |
|
|
2,069 |
|
|
|
628 |
|
Loss before income taxes |
|
|
(38,766 |
) |
|
|
(40,528 |
) |
|
|
(81,230 |
) |
|
|
(88,021 |
) |
Income tax provision |
|
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
— |
|
Net loss |
|
$ |
(38,766 |
) |
|
$ |
(40,528 |
) |
|
$ |
(81,230 |
) |
|
$ |
(88,021 |
) |
Net loss per share attributable
to ordinary shareholders—basic and diluted |
|
$ |
(0.78 |
) |
|
$ |
(1.15 |
) |
|
$ |
(1.65 |
) |
|
$ |
(2.53 |
) |
Weighted-average ordinary shares
used in computing net loss per share attributable to ordinary
shareholders—basic and diluted |
|
|
49,973,185 |
|
|
|
35,212,291 |
|
|
|
49,220,140 |
|
|
|
34,836,898 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Other comprehensive income
(loss): |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net loss |
|
$ |
(38,766 |
) |
|
$ |
(40,528 |
) |
|
$ |
(81,230 |
) |
|
$ |
(88,021 |
) |
Foreign currency translation |
|
|
— |
|
|
|
5 |
|
|
|
(120 |
) |
|
|
11 |
|
Comprehensive loss |
|
$ |
(38,766 |
) |
|
$ |
(40,523 |
) |
|
$ |
(81,350 |
) |
|
$ |
(88,010 |
) |
Investor Contact:Kate
Rausch617-949-4827krausch@wavelifesci.com
Media Contact:Alicia
Suter617-949-4817asuter@wavelifesci.com
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