Akari Therapeutics, Plc (Nasdaq: AKTX), a biopharmaceutical company
focused on innovative therapeutics to treat orphan autoimmune and
inflammatory diseases where the complement and/or leukotriene
systems are implicated, announced encouraging new data in both the
surface and the back of the eye.
“This positive initial data from our ophthalmology program
supports the potential efficacy of LTB4 and C5 inhibition in eye
surface and back-of-the-eye diseases. Nomacopan as a dual action
inhibitor of LTB4 and C5 has the potential to be a novel eye
therapy in multiple ophthalmic indications,” said Clive Richardson,
Interim Chief Executive Officer of Akari Therapeutics. “Akari
intends to continue development of nomacopan and long acting
nomacopan variants using both topical and intravitreal
administration.”
Poster Presentation at ARVO 2019Title:
Targeting the leukotriene B4 pathway and/or complement C5 via
dual-functional recombinant coversin (nomacopan) in Experimental
Autoimmune Uveitis (EAU)
In a poster to be presented at the Association for Research in
Vision and Ophthalmology (ARVO) annual meeting in Vancouver on
April 28, 2019, Dr Virginia Calder of the UCL Institute of
Ophthalmology, London, and Akari Therapeutics, will announce the
results of nomacopan and nomacopan variants in a preclinical model
of (EAU).
Uveitis is an inflammation of the uvea, the pigmented part of
the eye, which is caused by infection, autoimmunity, trauma, and
certain drugs or is secondary to other diseases. The prevalence of
uveitis is between 17 and 61 per 100,000 of the population and
autoimmune uveitis accounts for approximately 60% of all cases. It
is considered to be the major cause of preventable blindness in the
world.
In this experimental (EAU) model, long-acting variants of
nomacopan administered intravitreally demonstrated significant
improvement in clinical scoring versus control. This improvement
persisted until the end of the experiment (four days after the last
intravitreal injection) and was approximately equivalent to that of
intravitreally injected dexamethasone, a potent corticosteroid. The
long acting variants of nomacopan are PASylated (using a technology
licensed from XL-protein) and have the potential to have longer
residence time in the back of the eye to provide the extended
treatment time required for intravitreal injection.
Using confocal microscopy, C5a as well as LTB4 (BLT1) receptors
were reported in mouse retinal inflammatory cells for the first
time. In some cases these were co-located on the same cell
types. Long-acting intravitreal nomacopan, which inhibits both LTB4
and C5, demonstrated significant downregulation of T-helper 17
cells and IL-17A. T-helper 17 is an important inflammatory cell
associated with the release of inflammatory cytokines, in
particular IL-17, and is related to the progression of uveitis and
other back of the eye diseases.
Importantly, topical administration of nomacopan also
demonstrated mitigation of retinal disease as determined by
clinical scoring, and this initial signal will be investigated
further given the potential patient benefits.
These preclinical results highlight an opportunity to develop
nomacopan variants for intravitreal and topical use in uveitis and
other posterior inflammatory eye diseases such as AMD and diabetic
retinopathy. The novel dual inhibitory mechanism of action may
provide an alternative to corticosteroids, the current standard of
care for uveitis and avoid the adverse side effects that limit
their usefulness. Akari is now planning to evaluate the role of
topical and injected nomacopan in proliferative retinal
diseases.
A copy of the poster will be made available on the Company’s
website at www.akaritx.com following the presentation.
Phase I/II Clinical Trial in Patients with Atopic
Keratoconjunctivitis (AKC)
(AKC) is a serious orphan inflammatory disease of the eye
surface which, if inadequately treated, may lead to scarring of the
cornea and loss of vision. In at least 70% of cases it is
associated with severe dry eye disease (DED) which may lead to
further corneal damage and chronic discomfort. Current treatment,
if associated with DED, includes topical immunosuppressants
including cyclosporin A or lifitegrast, but in many cases systemic
immunosuppression becomes necessary. Furthermore, 15% to 30% of
patients experience post-instillation stinging and burning which
may lead to poor compliance.*
The ongoing open label Phase I/II clinical trial of nomacopan in
patients with moderate to severe AKC is enrolling patients at
Moorfields Eye Hospital in London. All patients must have received
cyclosporin A (standard of care) at maximal dose for at least three
months prior to entering, and continue to receive this dose for the
duration of the trial along with topical nomacopan twice daily for
56 days. The trial is divided into Part A and Part B. In Part A, as
this is the first time that nomacopan has been administered to the
eye, three patients will receive the drug in open label fashion to
assess safety and tolerability. After an independent data review,
an additional 16 patients will enter Part B, which is randomized,
placebo controlled and double-masked. Recruitment will be enhanced
by two additional sites: Bristol Eye Hospital and the Royal
Liverpool University Hospital, both in the UK. Akari anticipates
moving into Part B of the study by mid-year and completing by the
end of the year.
Encouraging interim data from the first two patients in Part A
showed no serious drug related adverse events and the patients also
reported that eye drops were well tolerated post installation,
which may reflect the iso-osmolarity and neutral pH of the
formulation.
The two patients demonstrated improvements in the primary
efficacy endpoint, a composite of 11 symptoms and signs with a
>35% improvement in composite efficacy score at day 14 of
treatment compared to baseline treatment on maximal cyclosporin. In
the first patient, who continues in the study, a change of the
primary efficacy endpoint toward baseline values was observed at
day 42 and is being assessed.
In both patients, there was a marked therapeutic improvement in
symptom discomfort from a mean of 2.5 at baseline on cyclosporin to
0.25 by Day 14 (where 0 is no discomfort and 3 is intolerable
discomfort).
Sajjad Ahmad, consultant ophthalmic surgeon at Moorfields Eye
Hospital, said: “We are pleased to be leading this first clinical
trial for atopic kerato-conjunctivitis at our NIHR funded
biomedical research centre. Early results are encouraging and
we’re looking forward to trying to identify a new treatment which
we hope will help prevent this debilitating disease.”
Ex-vivo study in allergic conjunctivitis
patients
Severe allergic conjunctivitis and severe AKC are both
associated with dry eye. Preclinical and ex-vivo studies
commissioned by Akari at the UCL Institute of Ophthalmology,
London, UK and at the School of Optometry and Vision Sciences,
University of New South Wales, Sydney, Australia have suggested
roles for complement C5 and LTB4 in the aetiology of eye surface
inflammatory disease. In particular, analysis of tear fluid from
allergic conjunctivitis patients showed 50-fold elevation of LTB4
levels compared to normal subjects.
*Refs: Holland E J et al. Ocul Surf. 2019 Mar 4.
pii: S1542-0124(18)30313-6; Trattler W et al. Clin Therapeutics
2006. (28, 11): 1849 – 1855.
About Akari Therapeutics
Akari is a biopharmaceutical company focused on developing
inhibitors of acute and chronic inflammation, specifically for the
treatment of rare and orphan diseases, in particular those where
the complement (C5) or leukotriene (LTB4) systems, or both
complement and leukotrienes together, play a primary role in
disease progression. Akari's lead drug candidate, nomacopan
(Coversin), is a C5 complement inhibitor that also independently
and specifically inhibits leukotriene B4 (LTB4) activity. Nomacopan
(Coversin) is currently being clinically evaluated in four
indications: bullous pemphigoid (BP), atopic keratoconjunctivitis
(AKC), thrombotic microangiopathy (TMA), and paroxysmal nocturnal
hemoglobinuria (PNH). Akari believes that the dual action of
nomacopan (Coversin) on both C5 and LTB4 may be beneficial in AKC
and BP. Akari is also developing other tick derived proteins,
including longer acting versions.
Cautionary Note Regarding Forward-Looking
Statements
Certain statements in this press release constitute
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995. These forward-looking
statements reflect our current views about our plans, intentions,
expectations, strategies and prospects, which are based on the
information currently available to us and on assumptions we have
made. Although we believe that our plans, intentions, expectations,
strategies and prospects as reflected in or suggested by those
forward-looking statements are reasonable, we can give no assurance
that the plans, intentions, expectations or strategies will be
attained or achieved. Furthermore, actual results may differ
materially from those described in the forward-looking statements
and will be affected by a variety of risks and factors that are
beyond our control. Such risks and uncertainties for our company
include, but are not limited to: needs for additional capital to
fund our operations, our ability to continue as a going concern;
uncertainties of cash flows and inability to meet working capital
needs; an inability or delay in obtaining required regulatory
approvals for nomacopan (Coversin) and any other product
candidates, which may result in unexpected cost expenditures; our
ability to obtain orphan drug designation in additional
indications; risks inherent in drug development in general;
uncertainties in obtaining successful clinical results for
nomacopan (Coversin) and any other product candidates and
unexpected costs that may result therefrom; difficulties enrolling
patients in our clinical trials; failure to realize any value of
nomacopan (Coversin) and any other product candidates developed and
being developed in light of inherent risks and difficulties
involved in successfully bringing product candidates to market;
inability to develop new product candidates and support existing
product candidates; the approval by the FDA and EMA and any other
similar foreign regulatory authorities of other competing or
superior products brought to market; risks resulting from
unforeseen side effects; risk that the market for
nomacopan (Coversin) may not be as large as expected; risks
associated with the departure of our former Chief Executive
Officers and other executive officers; risks associated with the
SEC investigation; inability to obtain, maintain and enforce
patents and other intellectual property rights or the unexpected
costs associated with such enforcement or litigation; inability to
obtain and maintain commercial manufacturing arrangements with
third party manufacturers or establish commercial scale
manufacturing capabilities; the inability to timely source adequate
supply of our active pharmaceutical ingredients from third party
manufacturers on whom the company depends; unexpected cost
increases and pricing pressures and risks and other risk factors
detailed in our public filings with the U.S. Securities and
Exchange Commission, including our most recently filed Annual
Report on Form 20-F filed with the SEC. Except as otherwise noted,
these forward-looking statements speak only as of the date of this
press release and we undertake no obligation to update or revise
any of these statements to reflect events or circumstances
occurring after this press release. We caution investors not to
place considerable reliance on the forward-looking statements
contained in this press release.
For more informationInvestor Contact:
Peter VozzoWestwicke Partners(443)
213-0505peter.vozzo@westwicke.com
Media Contact:
Sukaina Virji / Nicholas Brown / Lizzie SeeleyConsilium
Strategic Communications+44 (0)20 3709
5700Akari@consilium-comms.com
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