Clearside Biomedical, Inc. (NASDAQ:CLSD), a biopharmaceutical
company dedicated to developing and delivering treatments that
restore and preserve vision for people with serious back of the eye
diseases, announced today that multiple presentations were given at
the American Society of Retina Specialists (ASRS) Annual Meeting
and at the OIS Retina Summit at ASRS, which took place October 7 -
12, 2021 in San Antonio, TX.
“The data presented at both ASRS and last week’s
Retina Society meetings continue to demonstrate that our
proprietary in-office suprachoroidal space (SCS®) injection
treatment approach offers unprecedented targeted access to the back
of the eye to treat a variety of serious retinal diseases,” said
Thomas A. Ciulla, M.D., MBA, Chief Medical Officer and Chief
Development Officer. “Together with our partners, positive data has
been presented utilizing our SCS Microinjector® to deliver small
molecules, gene therapy, and virus-like drug conjugates in multiple
diseases, including uveitic macular edema, wet-AMD, diabetic
retinopathy, and choroidal melanoma. We remain encouraged by these
promising results as we continue to advance our own suprachoroidal
clinical development programs and broaden our reach in other
indications.”
Dr. Ciulla continued, “At ASRS, REGENXBIO
presented positive initial data from their ongoing Phase II
ALTITUDE™ trial of RGX-314 for the treatment of diabetic
retinopathy using our SCS Microinjector® for
in-office suprachoroidal delivery of their gene therapy. RGX-314
was well tolerated in 15 patients in Cohort 1 with no drug-related
serious adverse events and no intraocular inflammation observed. It
was also encouraging to see that there was a treatment effect after
only three months. In addition, our partner Aura Biosciences
presented their first data set on suprachoroidal delivery of
AU-011, their novel virus-like drug conjugate for the treatment of
primary choroidal melanoma, the most common intraocular tumor in
adults. In their Phase 2 trial, there have been no
treatment-related serious adverse events, dose limiting toxicities,
or grade 3 adverse events observed thus far. This favorable safety
profile to date may improve the therapeutic index, optimize
treatment parameters and potentially lead to improved visual
outcomes compared to intravitreal administration. These promising
results presented by our partners further support our belief in the
usefulness of our suprachoroidal injection platform and the SCS
Microinjector with a wide variety of drug candidates.”
Preceding the ASRS meeting, Dr. Ciulla presented
a corporate overview during the OIS Retina Summit highlighting the
potential of suprachoroidal delivery, as well CLS-AX (axitinib
injectable suspension), a proprietary suspension of axitinib, a
potent pan-VEGF inhibitor, which is currently being evaluated in a
Phase 1/2a clinical trial, entitled OASIS, for the treatment of
age-related macular degeneration (wet AMD).
ASRS presentations were as follows:
Title: Suprachoroidal
Administration of Small Molecule Suspensions:
Pre-Clinical Results Correlate to Clinical Trial
OutcomesLead Author: James C Major, Jr.,
MD, PhD, FASRSConclusions: Multiple small molecule
suspensions were evaluated in this study, including the
corticosteroid triamcinolone acetonide, the tyrosine kinase
inhibitor (TKI) axitinib, a complement inhibitor, and a plasma
kallikrein inhibitor. Suprachoroidal delivery of these agents was
investigated based on their potential for targeted delivery to
affected tissues for efficacy, compartmentalization away from
unaffected tissues for safety, and durability to address treatment
burden. Optical coherence tomography (OCT) images demonstrated a
definitive expansion of the suprachoroidal space both anteriorly
and posteriorly to the optic nerve head just minutes after
suprachoroidal injection. Suprachoroidal injection of small
molecule concentrations were similar in both the retina and
RPE/Choroid/sclera tissues. Favorable results from preclinical
studies of a triamcinolone acetonide suspension (CLS-TA) translated
to favorable clinical trial results for macular edema associated
with non-infectious uveitis. There is potential for similar
read-through of preclinical studies in the four current clinical
trials enrolling patients utilizing suprachoroidal injection with
the SCS Microinjector®: CLS-AX (axitinib injectable suspension) for
wet AMD; viral vector RGX-314 for wet AMD and diabetic retinopathy;
and viral-like drug conjugate AU-011 for choroidal melanoma.
Title: Safety of the
Suprachoroidal Injection Procedure Via Microinjector across Three
Retinal DisordersLead Author: Allen Hu,
MDConclusions: In this analysis, safety data from
the day of the procedure was compiled from 621 patients (1,274
suprachoroidal injections) in eight clinical trials utilizing
CLS-TA. The suprachoroidal injections were performed across three
disease states: noninfectious uveitis, diabetic macular edema, and
retinal vein occlusion. There were no serious adverse events (SAEs)
involving lens injury, suprachoroidal hemorrhage, endophthalmitis,
or retinal tears in any patient receiving one or more
suprachoroidal injections. Three SAEs of interest in both the study
and control arms were all deemed “not treatment related” by a
masked investigator. Overall, the safety profile of the
suprachoroidal injection procedure with a microinjector is not
clinically meaningfully different than the intravitreal injection
as reported in registration trials involving intravitreal anti-VEGF
injections alone.
Title: Comparison of
Suprachoroidal and Intravitreal Injection Flow Mechanics Analyzed
via Multimodal ImagingLead Author: Shree
Kurup, MD, FACPConclusions: This presentation
compared suprachoroidal and intravitreal injections using several
multimodal imaging diagnostics to demonstrate the injection flow
differences between the two procedures. During an intravitreal
injection, a bolus of dye was seen in the porcine vitreous cavity.
In contrast, during a suprachoroidal injection, spreading of the
dye was observed circumferentially and posteriorly towards the back
of the eye, between the sclera and choroid. In the study, an
endoscope was also placed within the vitreous cavity to film, in
real time, both intravitreal and suprachoroidal injections.
Suprachoroidal injection showed localized tissue depression, then
expansion with no needle penetration through the choroid and
retina. Imaging of suprachoroidal injections demonstrate acute
opening of the suprachoroidal space, circumferential, posterior
spread of injectate, and compartmentalization of injectate to
posterior tissues. In summary, these multimodal imaging
methodologies support the potential of suprachoroidal injections to
target affected tissue layers in chorioretinal disorders.
Title: OCT Anatomic
& Temporal Biomarkers in Uveitic Macular
EdemaLead Author: Dilraj S. Grewal,
MDConclusions: In clinical
practice, physicians often base treatment
decisions on best corrected visual acuity
(BCVA) and/or OCT assessment. There is limited information
on longitudinal structure-function correlations in uveitic
macular edema (UME). This study assessed these relationships,
focusing on baseline anatomic features with potential prognostic
value for visual response. This post hoc analysis of 198 eyes
evaluated two Phase 3, 24 week UME clinical trials with CLS-TA
(PEACHTREE and AZALEA). The study evaluated clinically relevant and
prognostic relationships between BCVA and OCT-assessed features of
macular edema including ellipsoid zone integrity, the presence and
location of cystoid spaces, and the presence and location of
subretinal fluid. Importantly, this analysis showed that eyes with
early anatomic response demonstrated better BCVA response at 24
weeks, and that anatomic response may precede visual response in
UME by one month or more among patients treated with CLS-TA. A
manuscript describing these results has received favorable review
in the American Journal of Ophthalmology, a prestigious
peer-reviewed Medline-indexed journal.
Title: Post Hoc
Analysis of Suprachoroidal CLS-TA versus Real World Rescue
Therapies for Uveitic Macular Edema: Safety and Visual
FunctionLead Author: Steven Yeh, M.D.
Conclusions: In this post hoc analysis of the
PEACHTREE trial, visual function and safety outcomes of unrescued
CLS-TA subjects were compared to rescued subjects in the control
group. Unrescued CLS-TA subjects experienced statistically
significant greater reduction in central subfield thickness and
trended towards greater improvement in BCVA compared with control
subjects rescued with therapies reflecting current clinical
treatment. Suprachoroidally administered CLS-TA also appeared to be
associated with a lower incidence of intraocular pressure-related
safety findings. This post hoc analysis provides a comparison of
CLS-TA to a “real world” mix of rescue treatments and corroborates
the pre-specified endpoints of the Phase 3 PEACHTREE study. A
manuscript describing these results is in press at Clinical and
Experimental Ophthalmology, a peer-reviewed Medline-indexed
journal.
Additional details on Clearside’s presentations
can be accessed on the Company’s website here.
About Clearside’s Suprachoroidal Space
(SCS®) Injection Platform and SCS
Microinjector®
Clearside’s patented, proprietary suprachoroidal
space (SCS®) injection treatment approach offers unprecedented
access to the back of the eye where sight-threatening disease often
occurs. The company’s unique platform is inherently flexible and
intended to work with established and new formulations of
medications. Clearside’s proprietary SCS Microinjector® can be used
to inject a wide variety of drug candidates that are specifically
formulated to be delivered via suprachoroidal injection. The SCS
Microinjector provides targeted delivery to potentially improve
efficacy and compartmentalization of medication to reduce or
eliminate toxic effects on non-diseased cells. The SCS
Microinjector is composed of a syringe and two 30-gauge hollow
microneedles of varying lengths, each less than 1.2 millimeters,
within a custom-designed hub that optimizes insertion and
suprachoroidal administration of drugs.
About XIPERE™ (triamcinolone acetonide
suprachoroidal injectable suspension)
XIPERETM (triamcinolone acetonide suprachoroidal
injectable suspension), formerly known as CLS-TA, is a proprietary
suspension of the corticosteroid triamcinolone acetonide formulated
for administration to the suprachoroidal space for the treatment of
macular edema associated with uveitis. Clearside’s patented
technology is designed to deliver drug to the suprachoroidal space
located between the choroid and the outer protective layer of the
eye, known as the sclera. Suprachoroidal injection enables the
rapid dispersion of medicine to the back of the eye, offering the
potential for the medicine to act longer and minimize harm to the
surrounding healthy parts of the eye. Bausch + Lomb, a leading
global eye health business of Bausch Health Companies Inc.
(NYSE/TSX: BHC), has the exclusive license for the
commercialization and development of XIPERE in the United States
and Canada. Arctic Vision, a specialty ophthalmology company based
in China, has the exclusive license for the commercialization and
development of XIPERE in Greater China, South Korea, Australia, New
Zealand, India and the ASEAN Countries. XIPERE is not yet approved
in any jurisdiction.
About Uveitis and Macular
Edema
Uveitis is a set of ocular inflammatory
conditions and is one of the leading causes of vision loss,
affecting approximately 350,000 patients in the United
States and more than one million worldwide. Approximately
one-third of these patients develop uveitic macular edema, a
build-up of fluid in the macula, the area of the retina responsible
for sharp, straight-ahead vision. Macular edema is the leading
cause of vision loss and blindness in uveitis patients and can
occur from uveitis affecting any anatomic location - anterior,
intermediate, posterior or pan. The uveitis market is expected to
grow by 2024 to nearly $550 million in the United
States and over $1 billion globally.
About CLS-AX (axitinib injectable
suspension)
CLS-AX (axitinib injectable suspension) is a
proprietary suspension of axitinib for suprachoroidal injection.
Axitinib is a tyrosine kinase inhibitor (TKI) currently approved to
treat renal cell cancer that achieves pan-VEGF blockade, directly
inhibiting VEGF receptors-1, -2, and -3 with high potency and
specificity. Clearside believes this broad VEGF blockade may have
efficacy advantages over existing retinal therapies by acting at a
different level of the angiogenesis cascade, and may benefit
patients who sub-optimally respond to current, more narrowly
focused anti-VEGF therapies. Suprachoroidal injection of this
proprietary suspension of axitinib has demonstrated meaningful
potential in preclinical studies in multiple species. Preclinical
results from Clearside and independent investigators have shown
pharmacodynamic effects with reduced growth of experimental
neovascularization and decreased fluorescein leakage. With
suprachoroidal administration of axitinib, there is the potential
to achieve prolonged duration and targeted delivery to affected
tissue layers. Clearside is developing CLS-AX as a long-acting
therapy for the treatment of wet AMD. CLS-AX is currently being
investigated in an ongoing US-based, multi-center, open-label,
dose-escalation, Phase 1/2a, safety and tolerability study,
entitled OASIS, in wet AMD patients, and additional information can
be found on https://clinicaltrials.gov (NCT04626128).
About the OASIS Phase 1/2a Clinical
Trial
OASIS is an open-label, dose-escalation Phase
1/2a trial in wet AMD patients to assess the safety and
tolerability of a single dose of CLS-AX administered by
suprachoroidal injection via Clearside’s SCS Microinjector®.
Eligible patients are those who demonstrate stable visual
acuity following two or more previous injections with an
intravitreal anti-VEGF agent. All enrolled patients undergo
diagnostic imaging on screening, followed by masked reading center
confirmation of persistent active disease.
Enrolled patients initially receive aflibercept
at the first visit followed by a single dose of CLS-AX at the
second visit one month later. The primary endpoint for the trial
will assess the safety and tolerability of CLS-AX for the three
months following the administration of CLS-AX, and secondary
endpoints will evaluate the pharmacokinetics, visual function,
ocular anatomy, and the need for additional treatment with
intravitreal aflibercept during the three-month period.
The study design is planned with 3 cohorts of
approximately 5 patients each (n=15). Cohort 2 participants
received a dose of 0.1 mg of axitinib delivered via suprachoroidal
injection. Dose escalation will proceed following review of the
Cohort 2 safety data by the Safety Monitoring Committee and their
recommendation to advance to the next higher dose cohort.
Additional information on the Phase 1/2a trial can be found
on https://clinicaltrials.gov (NCT04626128).
About Neovascular Age-Related Macular
Degeneration (wet AMD)
Age-related macular degeneration causes a
progressive loss of central vision and is the most common cause of
legal blindness in individuals over age 55. Wet AMD is generally
caused by abnormal blood vessels that leak fluid or blood into the
macula, the part of the retina responsible for central vision, and
accounts for the majority of vision loss in patients with this
disorder. In the U.S., approximately 11 million patients are living
with AMD, and about 20% have the wet form. Current treatments
require life-long, frequent injections to maintain efficacy. This
treatment regimen tends to cause a treatment burden for patients
resulting in reduced compliance and under-treatment leading to
potentially limited outcomes.
About Clearside Biomedical
Clearside Biomedical, Inc. is a
biopharmaceutical company dedicated to developing and delivering
treatments that restore and preserve vision for people with serious
back of the eye diseases. Clearside’s proprietary SCS
Microinjector® targets the suprachoroidal space (SCS®) and offers
unique access to the macula, retina and choroid where
sight-threatening disease often occurs. The Company’s SCS injection
platform is an inherently flexible, in-office, non-surgical
procedure, intended to provide targeted delivery to the site of
disease and to work with both established and new formulations of
medications. For more information, please visit
www.clearsidebio.com.
Cautionary Note Regarding
Forward-Looking Statements
Any statements contained in this press release
that do not describe historical facts may constitute
forward-looking statements as that term is defined in the Private
Securities Litigation Reform Act of 1995. These statements may be
identified by words such as “believe”, “expect”, “may”, “plan”,
“potential”, “will”, and similar expressions, and are based on
Clearside’s current beliefs and expectations. These forward-looking
statements include statements regarding the clinical development
and the potential benefits of XIPERE (formerly known as CLS-TA),
CLS-AX and other therapies using Clearside’s SCS Microinjector®, as
well as the potential to read-through results of preclinical
studies of CLS-TA to the four current clinical trials enrolling
patients utilizing suprachoroidal injection with the SCS
Microinjector®. These statements involve risks and uncertainties
that could cause actual results to differ materially from those
reflected in such statements. Risks and uncertainties that may
cause actual results to differ materially include uncertainties
inherent in the conduct of clinical trials, Clearside’s reliance on
third parties over which it may not always have full control,
uncertainties regarding the COVID-19 pandemic and other risks and
uncertainties that are described in Clearside’s Annual Report on
Form 10-K for the year ended December 31, 2020, filed with the U.S.
Securities and Exchange Commission (SEC) on March 15, 2021, and
Clearside’s other Periodic Reports filed with the SEC. Any
forward-looking statements speak only as of the date of this press
release and are based on information available to Clearside as of
the date of this release, and Clearside assumes no obligation to,
and does not intend to, update any forward-looking statements,
whether as a result of new information, future events or
otherwise.
Investor and Media Contacts:
Jenny Kobin Remy Bernarda ir@clearsidebio.com(678) 430-8206
Source: Clearside Biomedical, Inc.
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