Phase 2/3 Expansion Study to Include
No-Sham Control Arm in Alignment with FDA Draft Guidance on
Development of Gene Therapy Products for Retinal
Disorders
Nightstar Therapeutics plc (NASDAQ: NITE), a clinical-stage gene
therapy company developing treatments for rare inherited retinal
diseases, today provided an update on recent achievements and
upcoming clinical milestones and reported financial results for the
quarter ended September 30, 2018.
“We are pleased with the upcoming initiation of the Phase 2/3
expansion study in line with our previous guidance after being the
first sponsor to establish proof-of-concept in X-linked retinitis
pigmentosa,” said Dave Fellows, Chief Executive Officer. “The
modified Phase 2/3 expansion study is designed to be consistent
with recommendations in FDA’s draft guidance on the development of
gene therapy products for retinal disorders, which we believe will
allow us to expedite the development of NSR-RPGR.”
XIRIUS is a clinical trial consisting of an open-label, dose
escalation study followed by an expansion study. Enrollment of the
Phase 1 dose escalation study in the XIRIUS trial was completed in
August 2018, consisting of six cohorts of three patients each for a
total of 18 adult patients. On September 22, 2018, Nightstar
announced positive preliminary safety and efficacy data from the
XIRIUS trial for the first five cohorts (combined n=15) of the dose
escalation study at the EURETINA medical meeting. Six-month
follow-up data on all 18 patients in the dose escalation study is
expected to be available in the second quarter of 2019, with
one-year follow-up data expected to be available in the fourth
quarter of 2019.
The Phase 2/3 expansion study is designed to evaluate the safety
and efficacy of NSR-RPGR in patients with a diagnosis of XLRP due
to RPGR mutations, as confirmed by genetic testing. The primary
efficacy endpoint will evaluate changes in retinal sensitivity
following treatment with NSR-RPGR. Secondary endpoints include both
anatomical and functional endpoints of efficacy and safety similar
to those evaluated in the dose escalation study as well as
exploratory efficacy endpoints such as mobility maze
assessments. Approximately 45 patients across six
surgical centers in both the United States and the United Kingdom
will be enrolled. The eligibility criteria for the expansion study
will include patients with functional impairment as measured by
microperimetry and the presence of viable photoreceptors as
indicated by ellipsoid zone measurements on optical coherence
tomography. Patients will be randomized on a masked basis into one
of three study arms: approximately 15 patients receiving a
high-dose of NSR-RPGR in one-eye (2.5x10^11 genome particles, or
gp); approximately 15 patients receiving a low-dose of NSR-RPGR in
one-eye (5x10^10 gp); and approximately 15 patients receiving no
treatment (no-sham, parallel control arm). The two treatment groups
correspond to doses used in cohorts 5 and 3 of the dose escalation
study, respectively. A standardized eight-week steroid regimen will
be included to maximize any potential treatment benefit. The Phase
2/3 expansion study is expected to begin by the end of 2018.
Preliminary efficacy data is expected to be available in mid-2019,
which would serve as the basis for discussions with regulatory
agencies on potential Phase 3 requirements. One-year follow-up data
from the expansion study is expected to be available in
2020.
Business Highlights Include
- Appointment of Strategic Biotechnology Executive Paula
Cobb to Board of Directors in September 2018. Ms. Cobb
currently serves as the executive vice president of corporate
development at Decibel Therapeutics, Inc. and brings strategic,
worldwide commercialization experience in rare diseases, having led
teams to three new drug approvals and played key roles on four
product launches, which will be invaluable as Nightstar evolves
into a commercial-stage company.
- Positive Proof-of-Concept Data from Dose Escalation
Study in XIRIUS Trial for NSR-RPGR in XLRP in September
2018. NSR-RPGR data presented at the EURETINA 2018
Congress demonstrated proof-of-concept with durable dose-related
improvements seen as early as month 1 across multiple
microperimetry analyses. Preliminary efficacy responses were
observed in 5 out of 9 patients (56%) in cohorts 3, 4 and 5,
including durable improvements in overall macula sensitivity,
central 16 macula sensitivity and number of improved macula loci.
NSR-RPGR was well-tolerated with no dose limiting toxicities or
serious treatment-related adverse events.
- Inaugural R&D Day in September 2018. The
R&D day featured presentations on XLRP endpoints, positive
proof-of-concept data on NSR-RPGR from the XIRIUS dose escalation
study, program updates on NSR-REP1 for the treatment of
choroideremia and NSR-ABCA4 for the treatment of Stargardt disease,
as well as an overview of Nightstar’s hybrid manufacturing model
for gene therapy.
- Received Orphan Drug Designation for NSR-RPGR in
September 2018. NSR-RPGR was granted orphan drug
designation for the treatment of inherited retinal dystrophies due
to defects in the RPGR gene from the U.S. Food and Drug
Administration, or FDA, in the United States.
- Completion of Public Offering of 4,600,000 American
Depository Shares, or ADSs, in October 2018. The primary
offering of 4,600,000 ADSs, including the full exercise by the
underwriters of their overallotment option, at $18.00 per ADS,
resulted in estimated net proceeds to Nightstar of approximately
$77.1 million.
Anticipated Milestones for 2019 and 2020
- NSR-RPGR for X-Linked Retinitis
Pigmentosaº 2Q 2019: Six-Month
Follow-up Data from Dose Escalation
Studyº Mid-2019: Preliminary Efficacy
Data from Phase 2/3 Expansion Studyº 4Q
2019: One-Year Follow-up Data from Dose Escalation
Studyº 2020: One-Year Follow-up Data
from Phase 2/3 Expansion Study
- NSR-REP1 for
Choroideremiaº 1H
2019: Completion of Enrollment for Phase 3 STAR
Registrational Trial for
Choroideremiaº 2020: One-year Follow-up
Data from Phase 3 STAR Trial
Third Quarter 2018 Financial Results
Three Months Ended September 30, 2018 and 2017
Research and development expenses were $7.8 million for the
three months ended September 30, 2018, compared to $4.0 million for
the three months ended September 30, 2017. The increase of $3.8
million resulted primarily from increases in program-related
expenses of $1.1 million for NSR-REP1 and $1.7 million for
NSR-RPGR, as well as a $1.0 million increase in personnel-related
costs and a $1.0 million increase in indirect research and
development expenses. The increased expenses were partially offset
by an increase of $1.0 million of research and development tax
credits from Her Majesty’s Revenue & Customs, or HMRC. Research
and development personnel-related costs increased due to an
increase in headcount to support our growth and to assist in the
further development of our product candidates and pipeline. The
increase in research and development personnel-related costs
includes $0.2 million of additional non-cash share-based
compensation compared to the same period in 2017.
General and administrative expenses were $3.0 million for
the three months ended September 30, 2018, compared to $2.0 million
for the three months ended September 30, 2017. The increase of $1.0
million is mainly due to an increase in personnel-related costs.
General and administrative personnel-related costs increased due to
an increase in headcount to support our increased research and
development activities, growth of our company and our status as a
public company. The increase in general and administrative
personnel-related costs includes $0.3 million of additional
non-cash share-based compensation compared to the same period in
2017.
Net loss for the three-month period ended September 30, 2018 was
$7.6 million, or $0.27 basic and diluted net loss per ordinary
share, as compared to $8.2 million, or $0.38 basic and diluted net
loss per ordinary share, for the three-month period ended September
30, 2017.
Nine Months Ended September 30, 2018 and 2017
Research and development expenses were $22.0 million for the
nine months ended September 30, 2018, compared to $10.3 million for
the nine months ended September 30, 2017. The increase of $11.7
million resulted primarily from increases in program-related
expenses of $4.5 million for NSR-REP1 and $4.2 million for
NSR-RPGR, as well as a $3.7 million increase in personnel-related
costs and a $1.9 million increase in indirect research and
development expenses. The increased expenses were partially offset
by an increase of $2.6 million of research and development tax
credits from HMRC. Research and development personnel-related costs
increased due to an increase in headcount to support our growth and
to assist in the further development of our product candidates and
pipeline. The increase in research and development
personnel-related costs includes $1.0 million of additional
non-cash share-based compensation compared to the same period in
2017.
General and administrative expenses were $9.1 million for
the nine months ended September 30, 2018, compared to $3.4 million
for the nine months ended September 30, 2017. The increase of $5.7
million is mainly due to a $4.4 million increase in
personnel-related costs and a $1.3 million increase in consulting
and professional fees, including increased legal, accounting and
audit fees and insurance costs. General and administrative
personnel-related costs increased due to an increase in headcount
to support our increased research and development activities,
growth of our company and our status as a public company. The
increase in general and administrative personnel-related costs
includes $1.4 million of additional non-cash share-based
compensation compared to the same period in 2017.
Net loss for the nine-month period ended September 30, 2018 was
$30.0 million, or $1.07 basic and diluted net loss per ordinary
share, as compared to $15.9 million, or $0.84 basic and diluted net
loss per ordinary share, for the nine-month period ended September
30, 2017.
As of September 30, 2018, our cash, cash equivalents and
marketable securities totaled $100.8 million, compared to $129.4
million at December 31, 2017. As of September 30, 2018, there were
approximately 28.9 million ordinary shares outstanding. On October
2, 2018, Nightstar completed an underwritten public offering of
4,600,000 ADSs (representing the same number of ordinary shares),
including the full exercise by the underwriters of their option to
purchase additional ADSs, at a public offering price of $18.00 per
ADS, resulting in estimated net proceeds to Nightstar of
approximately $77.1 million, after deducting underwriting discounts
and commissions and estimated offering expenses.
About Nightstar
Nightstar is a leading clinical-stage gene
therapy company focused on developing and commercializing novel
one-time treatments for patients suffering from rare inherited
retinal diseases that would otherwise progress to blindness.
Nightstar’s lead product candidate, NSR-REP1, is currently in Phase
3 development for the treatment of patients with choroideremia, a
rare, degenerative, genetic retinal disorder that has no treatments
currently available and affects approximately one in every 50,000
people. Positive results from a Phase 1/2 trial of NSR-REP1 were
published in Nature Medicine in 2018, in The New
England Journal of Medicine in 2016, and in The
Lancet in 2014. Nightstar’s second product candidate,
NSR-RPGR, is currently being evaluated in a clinical trial known as
the XIRIUS trial for the treatment of patients with X-linked
retinitis pigmentosa, an inherited X-linked recessive retinal
disease that affects approximately one in every 40,000 people. In
September 2018, Nightstar announced positive preliminary safety and
efficacy data from the XIRIUS trial for the first five cohorts
(combined n=15) of the dose escalation study at the EURETINA
medical meeting.
For more information about Nightstar or its clinical trials,
please visit www.nightstartx.com.
About X-Linked Retinitis Pigmentosa (XLRP)
XLRP, a form of retinitis pigmentosa, is a rare inherited
X-linked recessive genetic retinal disorder primarily affecting
males. Approximately 70% of XLRP cases are due to variants in the
genes responsible for the production of RPGR. RPGR is involved in
the transport of proteins necessary for the maintenance of
photoreceptor cells. Loss of RPGR function in the retinal cells
causes the progressive loss of rod and cone photoreceptors, leading
to the loss of vision experienced by patients. The estimated
worldwide prevalence of XLRP due to RPGR variants is approximately
one in 40,000 people, which translates to approximately 17,000
patients in the United States and the five major European markets.
There are no treatments currently available for XLRP.
Nightstar is conducting a prospective, natural history
observational study, referred to as the XOLARIS study, to better
understand the progression of untreated XLRP in up to approximately
100 patients enrolled from approximately 23 centers in North
America and Europe.
Cautionary Language Concerning Forward-Looking
Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of
1995. The words “believe,” “anticipate,” “could,” “intend,”
“estimate,” “will,” “would,” “may,” “should,” “project,” “target,”
“track,” “expect” or other similar expressions are intended to
identify forward-looking statements, although not all
forward-looking statements contain these identifying words. All
statements contained in this press release other than statements of
historical facts are forward-looking statements, including, without
limitation: statements about our cash position and sufficiency of
capital resources to fund our operating requirements, trends and
other factors that may affect our financial results; our planned
and ongoing clinical trials for NSR-REP1 and NSR-RPGR, including
our Phase 3 STAR trial in choroideremia and our XIRIUS trial in
X-linked retinitis pigmentosa; potential results and timelines
relating to the dose escalation study and the Phase 2/3 expansion
study in the XIRIUS trial; the continued clinical development of
our pipeline; the timelines associated with our research and
development programs including the timing of patient enrollment and
the release of data from ongoing clinical trials and studies;
timelines, pathway and prerequisite activities, including
additional trials or studies, to filing for and receiving marketing
authorization for any of our product candidates from any regulatory
agency; the prevalence of patient populations for our targeted
indications; and the utility of the endpoints, including any
exploratory endpoints, in our clinical trials and the prior
preclinical and clinical data in determining future clinical
results. These forward-looking statements are based on management's
current expectations of future events as of the date of this
release and are subject to a number of substantial known and
unknown risks, uncertainties and other factors that may cause our
actual results, levels of activity, performance or achievements to
be materially different from the information expressed or implied
by these forward-looking statements, including those related to the
timing and costs involved in commercializing any product candidate
that receives regulatory approval; the initiation, timing and
conduct of clinical trials; the availability of data from clinical
trials and expectations for regulatory submissions and approvals;
whether interim results of a clinical trial will be predictive of
the final results of the trial; whether results of small or early
stage clinical trials will be predictive of the results of
later-stage trials; our scientific approach and general
development progress; the availability or commercial potential of
the our product candidates; the sufficiency of our cash resources;
and other risks and uncertainties set forth in our Report of
Foreign Private Issuer on Form 6-K furnished to the U.S.
Securities and Exchange Commission on September 25,
2018 and subsequent reports that we file with the U.S.
Securities and Exchange Commission. We may not actually achieve the
plans, intentions, estimates or expectations disclosed in our
forward-looking statements, and you should not place undue reliance
on our forward-looking statements. Actual results or events could
differ materially from the plans, intentions, estimates and
expectations disclosed in the forward-looking statements we make.
We anticipate that subsequent events and developments will cause
our views to change. We are under no duty to update any of these
forward-looking statements after the date of this press release to
conform these statements to actual results or revised expectations,
except as required by law. You should, therefore, not rely on these
forward-looking statements as representing our views as of any date
subsequent to the date of this press release. Any reference to our
website address in this press release is intended to be an inactive
textual reference only and not an active hyperlink.
Investors:Senthil Sundaram, Chief Financial
OfficerBrian Luque, Sr. Manager, Investor
Relationsinvestors@nightstartx.com
NIGHTSTAR THERAPEUTICS
PLC |
|
|
|
|
|
|
|
|
|
|
|
Consolidated Statements of Operations and
Comprehensive Loss |
|
(In thousands, except per share amounts) |
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months
Ended September
30, |
|
Nine Months
Ended September
30, |
|
|
|
2018 |
|
2017 |
|
2018 |
|
2017 |
|
Operating expenses: |
|
|
|
|
|
|
|
|
|
Research
and development |
|
$ |
7,845 |
|
|
$ |
3,983 |
|
|
$ |
21,961 |
|
|
$ |
10,275 |
|
|
General
and administrative |
|
|
3,019 |
|
|
|
2,025 |
|
|
|
9,119 |
|
|
|
3,432 |
|
|
Total
operating expenses |
|
|
10,864 |
|
|
|
6,008 |
|
|
|
31,080 |
|
|
|
13,707 |
|
|
Other
income (expense): |
|
|
|
|
|
|
|
|
|
Interest
and other income |
|
|
798 |
|
|
|
55 |
|
|
|
1,887 |
|
|
|
61 |
|
|
Other
Income (expense), net |
|
|
2,564 |
|
|
|
(2,258 |
) |
|
|
(1,097 |
) |
|
|
(2,258 |
) |
|
Total
other income (expense), net |
|
|
3,362 |
|
|
|
(2,203 |
) |
|
|
790 |
|
|
|
(2,197 |
) |
|
Loss
before benefit for income taxes |
|
|
(7,502 |
) |
|
|
(8,211 |
) |
|
|
(30,290 |
) |
|
|
(15,904 |
) |
|
Provision
for (benefit from) income taxes |
|
|
83 |
|
|
|
— |
|
|
|
(251 |
) |
|
|
— |
|
|
Net
loss |
|
|
(7,585 |
) |
|
|
(8,211 |
) |
|
|
(30,039 |
) |
|
|
(15,904 |
) |
|
|
|
|
|
|
|
|
|
|
|
Other
comprehensive income (loss) |
|
|
(2,733 |
) |
|
|
1,848 |
|
|
|
932 |
|
|
|
3,570 |
|
|
Total
comprehensive loss |
|
$ |
(10,318 |
) |
|
$ |
(6,363 |
) |
|
$ |
(29,107 |
) |
|
$ |
(12,334 |
) |
|
Basic
and diluted net loss per ordinary share |
|
$ |
(0.27 |
) |
|
$ |
(0.38 |
) |
|
$ |
(1.07 |
) |
|
$ |
(0.84 |
) |
|
Weighted
average basic and diluted ordinary shares |
|
|
28,139 |
|
|
|
21,514 |
|
|
|
27,975 |
|
|
|
18,858 |
|
|
|
|
|
|
|
|
|
|
|
|
NIGHTSTAR THERAPEUTICS
PLC |
|
|
|
|
|
|
|
Consolidated Balance Sheets |
|
(In thousands) |
|
|
|
|
|
|
|
|
|
September 30, |
|
December 31, |
|
|
|
2018 |
|
2017 |
|
Assets |
|
|
|
|
|
Current
assets: |
|
|
|
|
|
Cash and cash
equivalents |
|
$ |
45,974 |
|
$ |
129,404 |
|
Marketable securities |
|
|
54,800 |
|
|
— |
|
Prepaid
expenses and other assets |
|
|
12,531 |
|
|
5,438 |
|
Total
current assets |
|
|
113,305 |
|
|
134,842 |
|
Property
and equipment, net |
|
|
534 |
|
|
355 |
|
Other
assets |
|
|
632 |
|
|
— |
|
Total
assets |
|
$ |
114,471 |
|
$ |
135,197 |
|
|
|
|
|
|
|
Liabilities and shareholders’ equity |
|
|
|
|
|
Current
liabilities: |
|
|
|
|
|
Accounts
payable |
|
$ |
4,423 |
|
$ |
3,196 |
|
Accrued
expenses and other liabilities |
|
|
10,340 |
|
|
6,189 |
|
Total
current liabilities |
|
|
14,763 |
|
|
9,385 |
|
Total
liabilities |
|
|
14,763 |
|
|
9,385 |
|
|
|
|
|
|
|
Total
shareholders’ equity |
|
|
99,708 |
|
|
125,812 |
|
Total
liabilities and shareholders’ equity |
|
$ |
114,471 |
|
$ |
135,197 |
|
|
|
|
|
|
|
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