-Interim Phase 2 PNH data demonstrate
positive response with Coversin™-Phase 3 PNH
program expected to commence in 4Q2017-Data from
preclinical aHUS model demonstrates positive
results-New preclinical data demonstrates positive
response of Coversin’s combined C5 and LTB4 therapy in skin and eye
models -Phase 2 programs in Mucous Membrane
Pemphigoid (eye) and Bullous Pemphigoid (Skin) expected to commence
in 1Q2018
Akari Therapeutics (NASDAQ:AKTX), an emerging growth,
clinical-stage biopharmaceutical company, announced that it will
present data from an interim analysis of its ongoing Phase 2 trial
of Coversin in paroxysmal nocturnal hemoglobinuria (PNH), as well
as preclinical data for additional indications and other
opportunities, at today’s Research and Development Day.
Positive Interim Phase 2 data in
PNH
In this 90 day, open label Phase 2 trial
conducted at five centers in the EU, five patients with PNH who had
not received prior anti-complement therapy were enrolled and
treated with Coversin self-administered subcutaneous injections
twice a day for approximately the first month and then switched to
once daily injections. The primary endpoint in this trial is
reduction in serum LDH to ≤1.8 X ULN or 500 I U/L whichever is the
lower from day 1 (pre-dose) to day 28. Secondary endpoints are LDH
at days 60 and 90, hemoglobin, CH50, quality of life, and
transfusion independence. The objectives of our Phase 2 study are
to validate the safety and efficacy of Coversin, confirm
convenience of our dosing regimen, and study dose ranging to
identify the correct treatment dose in advance of Phase 3.
The 4 patients who remain on Coversin are
characterized, to date, by:
- Symptom free
- LDH reductions 1.3, 1.4, 1.5 and 1.8X ULN
- No transfusions (2 of the 4 patients received transfusions in
the 3 months prior to the study)
- CH50 below level of quantification (from day 1)
- Once daily subcutaneous self-administration
- No neutralizing antibodies
- No serious adverse events (SAEs)
In this dose ranging Phase 2 study, the protocol
allowed for patients to be updosed from the 30mg starting dose. Of
the 4 patients continuing on Coversin: the first patient’s
LDH went from 2.4X ULN at baseline to 2.1X ULN on the
starting dose, was updosed to 45 mg and achieved a reduction to
1.3X ULN on day 28 and remains on 45mg once daily injections; the
second patient with an LDH of 7.5X ULN at baseline, achieved a
reduction to 1.4X ULN on day 28 with the starting dose, and remains
on 30mg once daily injections; the third patient’s LDH went from
3.3X ULN at baseline to 2.4X ULN on the starting dose, was updosed
to 45 mg and achieved a reduction to 1.5X ULN on day 60 and
remains on 45mg once daily injections; and the fourth patient who
just reached the 6 week mark for this interim analysis achieved an
LDH reduction from 5.6 X ULN at baseline to 1.8X ULN on day 40 on
the starting dose, and was updosed to 45mg on day 48 and continues
on once daily injections. All 4 patients achieved on day 1 and
throughout the trial a CH50 below the lower limit of quantification
(“<LLQ”).
A fifth patient with an LDH of 3.7 X ULN at
baseline achieved the primary endpoint at day 14, but was withdrawn
from the trial at day 43 due to a suspected co-morbidity
unrelated to treatment, which would have excluded the patient
from the trial protocol. While on Coversin, the patient met
the primary endpoint (day 14), and achieved and maintained a CH50
<LLQ (day 1) but clinical response fluctuated and did not
stabilize. After withdrawal, the patient switched to
eculizumab. On eculizumab, LDH decreased to below 1.5X ULN and the
patient experienced other clinical complications.
As reported previously, an eculizumab-resistant PNH patient had
been under treatment with subcutaneous Coversin for over 14 months
under an approved clinical protocol. The patient continues to
self-administer Coversin and continues to demonstrate complete
complement inhibition without any change in dose. The
patient’s most recent reported LDH was below 1.3 X ULN. Further,
there have been no signs of neutralizing antibodies.
All patients are comfortable with self-dosing
and by the end of May, we plan to have the four continuing patients
from this Phase 2 and the one patient from the eculizumab resistant
protocol on long term treatment in our long term open label safety
trial. Akari is planning to initiate its Phase 3 program in PNH in
the fourth quarter of 2017 and anticipates initial Phase 3 data
1Q2019.
aHUS
Recent studies with Coversin have demonstrated
positive results in a preclinical model of atypical hemolytic
uremic syndrome (aHUS) conducted by Prof. Giuseppe Remuzzi and
colleagues Marina Noris and Miriam Galbusera at the Mario Negri
Institute for Pharmacological Research in Bergamo, Italy, and the
Clinical Research Center for Rare Diseases "Aldo e Cele Dacco" of
the same institute, a European center for the study of aHUS. In a
well-established ex vivo model testing sera of patients with aHUS,
Coversin demonstrated a statistically significant (p<0.001)
reduction in membrane attack complex (MAC) deposition on
endothelial cells when activated by sera of patients with active
aHUS, at least as well as eculizumab. Akari expects to initiate its
Phase 2 trial in aHUS in 2Q2017, and anticipates Phase 2 aHUS data
2Q2018.
New data demonstrating Coversin C5 and
LTB4 dual activity in eye and skin models
Akari will present new data on its clinical
development plan for Coversin based on its dual C5/LTB4 inhibition,
focusing on new clinical indications in the eye and skin.
Results in a rodent model of Experimental Immune
Conjunctivitis (EIC), undertaken at the world leading Moorfields
Hospital Institute of Ophthalmology, showed that Coversin
demonstrated significant anti-inflammatory activity with both C5
and LTB4 inhibition believed to play a role. In this preclinical
model of severe eye surface inflammation, Coversin, applied
topically, resulted in a statistically significant reduction (64%,
p<0.001) in late phase inflammation versus placebo.
In a pre-clinical mouse model of bullous
pemphigoid (a blistering disease of the skin), where both LTB4 and
C5 are thought to be dysregulated, Coversin demonstrated a
statistically significant reduction (~60%, p=0.002) in affected
area with Coversin compared to placebo and steroids.
Based on these results, Akari, while continuing
to develop Coversin in PNH and aHUS, also intends to focus on new
indications for Coversin in diseases where both C5 and LTB4 are
believed to be involved. Akari expects to commence in 1Q2018
randomized, double blind Phase 2 trials in patients with bullous
pemphigoid who are refractory to oral steroids as well in mucous
membrane pemphigoid (eye) and anticipates Phase 2 data from
these trials in 4Q2018.
Pipeline
Akari will present an update on its pipeline of
new molecules including:
- new data in an ex vivo model testing activity in the
alternative pathway of Complement of its long acting version of
Coversin, PAS Coversin, which is designed for weekly dosing,
demonstrated that PAS Coversin could potentially be more potent
than Coversin and eculizumab . This data will be presented by
Professor Arne Skerra, Professor of Biological Chemistry at the
University of Munich and Chairman of XL-protein GmbH. Akari
anticipates a Phase 1 trial for PAS Coversin to commence in
3Q2018.
- positive data in a range of ex vivo lung models using a new
Akari molecule that binds only to LTB4. This opens up a range of
new inflammatory target conditions for Akari where LTB4
dysregulation is potentially the primary pathophysiology of
disease. This data will be presented by Dr Robert Snelgrove,
National Heart and Lung Institute, Imperial College London whose
particular expertise lies in LTB4 and lung inflammation.
Akari
anticipates further preclinical pipeline data in 3Q2017.
WebcastThe R&D Day
presentation, scheduled to begin at 8:00am EDT today, April 24,
2017, will be webcast live and can be accessed by following the
link on the homepage of our website (www.akaritx.com) as well as
through the “Link to Simulcast for April 24th R&D Day” which
appears on the left side of the “Investor Relations” section of
Akari’s website.
About Akari Therapeutics Plc
Akari is a clinical-stage biopharmaceutical
company focused on the development and commercialization of
life-transforming treatments for a range of rare and orphan
autoimmune and inflammatory diseases caused by dysregulation of
complement C5 and Leukotriene B4 (LTB4), including paroxysmal
nocturnal hemoglobinuria (“PNH”), atypical Hemolytic Uremic
Syndrome (“aHUS”), and Guillain Barré syndrome (“GBS”). Akari’s
lead product candidate, Coversin™ complement inhibitor, a
second-generation complement inhibitor, acts on complement
component-C5, preventing the release of C5a and the formation of
C5b–9 (also known as the membrane attack complex or MAC), and
independently also inhibits LTB4 activity. C5 inhibition is growing
in importance in a range of rare autoimmune diseases related to
dysregulation of the complement component of the immune system,
including PNH, aHUS, and GBS. Exploiting the power of nature, Akari
is also developing other tick derived proteins and expects to bring
additional compounds to clinical trials over the next several
years. The pipeline is focused on developing bioengineered versions
of native tick salivary proteins that act as anti-inflammatory
compounds allowing the tick to remain on its host. These compounds
include PGP sparing LTB4 inhibitors, classical and alternative
complement inhibitors, anti-histamines, and serotonin inhibitors as
examples. Akari is also developing engineered forms that allow for
potential oral absorption, as, for example, a potential orally
absorbed C5 inhibitor, and tissue specific proteins, as, for
example, Coversin™ that acts specifically at the neuromuscular
junction for diseases like myasthenia gravis.
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, an inability
or delay in obtaining required regulatory approvals for Coversin
and any other product candidates, which may result in unexpected
cost expenditures; risks inherent in drug development in general;
uncertainties in obtaining successful clinical results for Coversin
and any other product candidates and unexpected costs that may
result therefrom; failure to realize any value of 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 Coversin may not be as large as expected; 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; our inability to obtain additional
capital on acceptable terms, or at all; unexpected cost increases
and pricing pressures; uncertainties of cash flows and inability to
meet working capital needs; and risks and other risk factors
detailed in our public filings with the U.S. Securities and
Exchange Commission, including our Annual Report on Form 20-F filed
on March 31, 2017. 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.
Contact:
Investor Contact:
The Trout Group
Lee Stern
lstern@troutgroup.com
646–378–2922
Media Contact:
Susan Forman / Laura Radocaj
Dian Griesel Int'l.
(212) 825-3210
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