Clinical Data on EBI-005 Demonstrated Improvements in Signs and
Symptoms in Patients with Dry Eye Disease through IL-1 Inhibition
Preclinical Data on EBI-029 Demonstrated Inhibition of IL-6 as a
Validated Target for Treating Diabetic Macular Edema
CAMBRIDGE, Mass.--(BUSINESS WIRE)--
Eleven Biotherapeutics (NASDAQ: EBIO), a clinical-stage
biopharmaceutical company discovering and developing protein
therapeutics to treat diseases of the eye, today announced the
presentation of data for two of its novel, protein therapeutics
demonstrating the key role of cytokine biology to target both front and
back of eye diseases at the Association for Research in Vision and
Ophthalmology (ARVO) 2014 Annual Meeting in Orlando, FL. Clinical data
on Eleven's lead drug candidate, EBI-005, the first IL-1 (Interleukin-1)
signaling inhibitor designed for topical ocular administration,
demonstrated improvements in signs and symptoms of dry eye disease
(DED), including reduction in ocular pain and artificial tear use. In
addition, preclinical data on EBI-029, an IL-6 (Interleukin-6) inhibitor
optimized for localized ocular administration in diabetic macular edema
(DME), has demonstrated that EBI-029 potently inhibits IL-6 signaling in
vitro. IL-6 is a cytokine that has previously been shown to be
upregulated in DME, contributing to the angiogenic and inflammatory
components of the disease and correlating with disease severity. By
inhibiting IL-6, EBI-029 could offer an alternative to current standard
of care, including anti-VEGF therapies.
"Proteins designed specifically as ophthalmic therapies represents an
innovative approach to treating diseases of the eye with high unmet
need," said Abbie Celniker, PhD, Chief Executive Officer of Eleven
Biotherapeutics. "These data demonstrate Eleven's ability to target both
front and back of eye disease by leveraging our extensive cytokine
Dr. Celniker continued, "The data we are presenting on our lead product
candidate, EBI-005, underscores its potential utility in treating dry
eye disease by inhibiting the cytokine IL-1, a key mediator of
inflammation in the eye. Likewise, a correlation has been previously
observed between increased IL-6 levels and disease severity in diabetic
macular edema, including scenarios where VEGF inhibition treatment has
been suboptimal. These data suggest the potential of IL-6 blockade with
EBI-029 in treating diabetic macular edema and support further
development of EBI-029 either as a stand-alone drug or in combination
with VEGF blockade."
EBI-005, a topical IL-1 receptor antagonist for the treatment of ocular
surface disease, is currently being evaluated in a pivotal Phase
3 clinical study in subjects with DED and a Phase 2 clinical study in
subjects with allergic conjunctivitis. EBI-029, an IL-6 receptor
antagonist for localized intravitreal treatment of back of eye disease,
is currently in preclinical development for the treatment of DME.
In a poster presentation entitled "Optimized IL-6 Blockade for the
Treatment of Diabetic Macular Edema," Eleven Biotherapeutics researchers
presented preclinical data which demonstrated that local IL-6 inhibition
potently inhibits IL-6 signaling.
Local IL-6 inhibition with a surrogate anti-IL-6 antibody
significantly reduced abnormal neovascularization in a rat model of
choroidal neovascularization (CNV), supporting the role of IL-6 in
pathologic ocular angiogenesis.
Intravitreal (IVT) administered anti-IL-6 antibody significantly
reduced lesion size compared to the vehicle control (p = 0.0054 on
Day 15 and p = 0.0005 on Day 22).
There was no significant difference between the IL-6 inhibition
and anti-VEGF positive control.
EBI-029, a novel antibody against human IL-6, potently inhibits IL-6
signaling and has novel biophysical properties, including improved
stability and solubility and minimized systemic exposure, for
high-concentration IVT administration.
The humanized antibody EBI-029 binds human IL-6 with 200 pM
affinity and potently blocks IL-6 signaling in cellular assays.
EBI-029 is thermally stable (Tm ~ 80 °C) and has no measurable
aggregation at 20 mg/mL.
Full-length variants of EBI-029 have been engineered to further
extend vitreal residence and reduce systemic exposure.
In a poster presentation entitled "Topical Interleukin-1 (IL-1) Receptor
Inhibition Reduces Ocular Pain" Eleven Biotherapeutics researchers
presented clinical data which demonstrated that inhibition of IL-1
reduced frequency of painful or sore eyes suggesting that inhibiting
IL-1 signaling in the eye with EBI-005 may directly affect ocular pain
associated with DED.
A Phase 1a/Phase 2b clinical study of 74 subjects with moderate to
severe DED treated topically with EBI-005 resulted in a clinically
meaningful improvement in Ocular Surface Disease Index
(OSDI)-Pain/Sore eye score at six weeks compared to baseline scores.
In this Phase 1a/2b study, treatment with EBI-005 for six weeks
resulted in a clinically relevant reduction in the frequency of
painful or sore eye compared to vehicle treatment.
Treatment with EBI-005 was safe and well-tolerated and
importantly, did not decrease corneal sensation.
The effect was seen as early as two weeks post initiation of
therapy with no plateau of effect at 6 weeks
The effect was greater over time compared to the vehicle control.
The EBI-005 Phase 3 co-primary endpoint in Dry Eye is the painful or
sore eyes question of the OSDI.
In a poster presentation entitled "Reduced Rescue Artificial Tear Use in
Subjects Using a Topical Interleukin-1 (IL-1) Receptor-1 (R1) Blocker
for Ocular Treatment of Dry Eye Disease (DED)" Eleven Biotherapeutics
researchers presented data from a Phase 1/2b study which demonstrated
that EBI-005 treated subjects used fewer rescue artificial tears than
vehicle-control treated subjects.
Subjects treated with EBI-005 used fewer rescue artificial tears than
vehicle control treated subjects over the six week study period.
Mean rescue artificial tear use over the six week study period was
11.1 vials for subjects receiving EBI-005 and 31 vials for
subjects receiving vehicle control (p value=.005).
Median rescue artificial tear use over the six week period was 1
vial for subjects receiving EBI-005 and 10.5 vials for subjects
receiving vehicle control.
There was a lower percentage of users of large amounts of rescue
artificial tears (defined as user of more than 50 vials during the
six week study period) among subjects receiving EBI-005 (5% or 2
of 39) compared with vehicle control (35% or 9 of 26) (p value=
Of the 10 heaviest artificial tear users, eight (80%) were
subjects receiving vehicle.
Vehicle control treated subjects used more rescue artificial tears
than those who received EBI-005 at all time points, with the
largest difference seen at four weeks.
Rescue artificial tear use was similar between EBI-005 treated and
those treated with vehicle control at two weeks for subjects with
baseline OSDI scores of less than 50 (EE50 population). At four
and six weeks, however, subjects receiving vehicle control used
more rescue artificial tears than those who received EBI-005.
Eleven Biotherapeutics' most advanced product candidate is EBI-005,
which was designed, engineered and generated using the Company's AMP-Rx
platform and is being developed as a topical treatment for dry eye
disease and allergic conjunctivitis. In 2013, Eleven Biotherapeutics
completed a Phase 1b/2a clinical trial of EBI-005 in patients with
moderate to severe dry eye disease. The EBI-005 program is based on the
role that elevated levels of the inflammatory cytokine interleukin-1, or
IL-1, play in the initiation and maintenance of the inflammation and
pain associated with dry eye disease and the redness and itching
associated with allergic conjunctivitis. EBI-005 is currently being
evaluated in a pivotal Phase 3 clinical study in subjects with dry eye
disease and a Phase 2 clinical study in subjects with allergic
About Eleven Biotherapeutics
Eleven Biotherapeutics, Inc. is a clinical-stage biopharmaceutical
company with a proprietary protein engineering platform, called AMP-Rx,
that it applies to the discovery and development of protein therapeutics
to treat diseases of the eye. The Company's therapeutic approach is
based on the role of cytokines in diseases of the eye, the Company's
understanding of the structural biology of cytokines and the Company's
ability to rationally design and engineer proteins to modulate the
effects of cytokines. Cytokines are cell signaling molecules found in
the body that can have important inflammatory effects.
Cautionary Note on Forward-Looking Statements
Any statements in this press release about future expectations, plans
and prospects for the Company, including statements about the Company's
strategy, future operations, clinical development of the Company's
therapeutic candidates, including expectations regarding timing of
initiation of clinical trials, patient enrollment and availability of
results, regulatory requirements for initiation of clinical trials and
registration of product candidates, and other statements containing the
words "anticipate," "believe," "estimate," "expect," "intend," "may,"
"plan," "predict," "project," "target," "potential," "will," "would,"
"could," "should," "continue," and similar expressions, constitute
forward-looking statements within the meaning of The Private Securities
Litigation Reform Act of 1995. Actual results may differ materially from
those indicated by such forward-looking statements as a result of
various important factors, including: the uncertainties inherent in the
initiation and conduct of clinical trials, availability and timing of
data from ongoing clinical trials, whether results of early clinical
trials will be indicative of the results of future trials, uncertainties
associated with regulatory review of clinical trials and applications
for marketing approvals and other factors discussed in the "Risk
Factors" section of the Company's prospectus filed with the Securities
and Exchange Commission pursuant to Rule 424(b)(4) on February 6, 2014.
In addition, the forward-looking statements included in this press
release represent the Company's views as of the date hereof. The Company
anticipates that subsequent events and developments will cause the
Company's views to change. However, while the Company may elect to
update these forward-looking statements at some point in the future, the
Company specifically disclaims any obligation to do so. These
forward-looking statements should not be relied upon as representing the
Company's views as of any date subsequent to the date hereof.
Cameron Wheeler, PhD, 617-858-0927
Gina Nugent, 617-460-3579
Source: Eleven Biotherapeutics
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