Akari Therapeutics, Plc (Nasdaq: AKTX), a Phase III
biopharmaceutical company focused on innovative therapeutics to
treat orphan autoimmune and inflammatory diseases where the
complement and/or leukotriene systems are implicated, announces its
intention to develop nomacopan as a potential treatment for
COVID-19 pneumonia through integrated clinical trial programs in
U.S., U.K. and Brazil.
Clive Richardson, Chief Executive Officer of Akari Therapeutics,
said, “There remains an overwhelming need for more effective
treatment of hospitalized COVID-19 pneumonia patients. I am pleased
nomacopan has been selected by the U.K.’s AGILE clinical program. I
can also report that we are now treating patients in Brazil and the
U.S. in initial proof of principle studies, with the objective of
progressing into randomized clinical studies in the fourth quarter
of 2020. We believe nomacopan has the potential to inhibit the key
proinflammatory and prothrombotic pathways driving this disease,
and hence meaningfully reduce morbidity and mortality in this
COVID-19 patient group.”
Scientific rationale for potential use of nomacopan in
COVID-19 pneumonia
Nomacopan’s dual complement (C5) and leukotriene (LTB4)
inhibition blocks several key inflammatory pathways that drive
COVID-19 pneumonia.
Terminal complement activation by formation of C5a and the
membrane attack complex (C5b9) is associated with direct vascular
damage, microthrombi and long-term damage to the lung and other
organs in COVID-19 patients1. A causative role for complement
activation has been shown in other inflammatory diseases with
shared pathophysiological components, such as hematopoietic stem
cell transplant-related thrombotic microangiopathy (TMA-HSCT)2 in
which Akari has an open Phase III Investigational New Drug (IND)
application.
Neutrophil accumulation in the lungs is another key feature of
COVID-19 pneumonia, resulting in ‘cytokine storm syndrome’ and
associated epithelial damage in lung and other organs.
Leukotriene (LTB4) is one of the most potent known chemo
attractants of neutrophils and other neutrophil chemo-attractants
appear to rely on LTB4 synthesis for recruitment of neutrophils
from distal sites. Leukotriene inhibitors are approved for
treatment of asthma and are being tested in COVID-19 pneumonia3 due
to their ability to block multiple cytokines. Cytokines and
chemokines inhibited by nomacopan4 include GM-CSF, IL1 alpha,
IL1beta, IL2, IL-6, IL17, TNF, RANTES, MCP1, MIP1alpha andMIP1beta
all of which have been reported to be elevated in COVID-19
pneumonia patients5.
The potential additive benefits of both C5 and LTB4 inhibition
by nomacopan have previously been demonstrated in preclinical
models of viral induced acute respiratory distress syndrome (ARDS)
with reduced inflammation and mortality6. Moreover, the combined
inhibition of both C5 and LTB4 demonstrated by nomacopan was
superior to inhibition by either C5 or LTB4 alone in a mouse model
of acute lung inflammation, highlighting the additive effect of
inhibiting both these innate immune pathways7.
Akari believes that this inhibition of multiple inflammatory
pathways distinguishes nomacopan from other potential therapies
focused on a single mechanism of action. In addition to nomacopan’s
fast onset of action, the rapid normalization of complement and
LTB4 levels at the end of treatment has the potential to avoid the
risks of longer-term immunosuppression typical of monoclonal
antibodies.
Staged clinical development plan with nomacopan for the
treatment of COVID-19 pneumonia
Akari’s strategy for advancing clinical development of nomacopan
as a potential COVID-19 pneumonia treatment includes: (1)
identifying biomarkers to optimize patient selection; (2)
completing initial proof of principle studies in hospitalised
COVID-19 patients; (3) conducting integrated randomized clinical
trials in the U.S., Brazil and the U.K, and (4) seeking regulatory
approval if the results of the randomized clinical trials
satisfactorily demonstrate the safety and efficacy of nomacopan as
a treatment of COVID-19 pneumonia.
An observational study relating to biomarkers that may identify
COVID-19 patients who are particularly suitable for nomacopan
treatment is ongoing in the U.K. Data has been collected on
approximately 50 patients with COVID-19 pneumonia and analysis of
the samples is in process with data expected early in the fourth
quarter of 2020. The second part of the program, a longitudinal
study taking repeat samples from COVID-19 patients with worsening
disease is ongoing.
Initial POP treatment in patients with COVID-19 pneumonia via
expanded access programs (EAPs) are ongoing in the US. In Brazil,
recruitment to a similar POP treatment study has been completed and
the data will be reviewed for safety by the Data and Safety
Monitoring Board (DSMB). If the DSMB concludes that the drug is
safe, the program in Brazil will progress to a randomized study in
the fourth quarter of 2020.
These COVID-19 programs build on the existing Akari clinical
experience in the use of nomacopan, underpinned by 35 cumulative
patient-years of nomacopan safety data with no reported drug
related SAEs, and clinical response across a range of inflammatory
conditions in Phase II and Phase III development.
Planned randomized clinical studies
Akari intends to conduct multiple randomized controlled studies
in the U.S., U.K. and Brazil based on the same clinical study
design.
In the U.S., Akari is collaborating on a proposed
investigator-led multi-center randomized study the commencement of
which is subject to U.S. Food and Drug Administration (FDA)
approval of a related IND. In Brazil, the POP study is expected to
progress into a similar randomized trial, pending successful
outcome of the DSMB review.
In the U.K., nomacopan has been selected by the AGILE platform
as a new potential treatment for patients with COVID-19 pneumonia.
AGILE is a dedicated therapeutic development platform supported by
the Wellcome Trust and UNITAID to identify, support and develop
promising treatments for COVID-19. The AGILE program is sponsored
by the Royal Liverpool Hospital, U.K. With AGILE’s support,
Akari is also exploring extending the nomacopan COVID-19 clinical
program into multiple countries in Africa, with potential patient
recruitment starting in the fourth quarter of 2020.
Subject to additional comments from regulators, the trial
protocols for the planned randomized clinical trials would provide
for patients to be randomized 2:1 nomacopan plus standard of care
(SoC) or SoC alone, with an initial target of around 60 patients in
each of the individual study settings. Patients would be on
supportive oxygen (not intubated) and be recruited following
admission to hospital. The primary endpoint is time to
normalization of oxygen, while the secondary endpoint will include
need for intubation and mortality. Patients will receive a daily
subcutaneous dose of nomacopan for up to 14 days, with study
monitoring and completion after two months. The SoC arm for the
trials incorporates the latest treatments where available,
including dexamethasone and remdesivir, both of which have a
different mode of action to nomacopan and as such, nomacopan has
the potential to add additional efficacy to either or both of these
treatments. In examining the efficacy of nomacopan Akari expects to
consider the totality of the data across these studies using the
same endpoints.
Professor Tim Higenbottam, President Faculty of the
Pharmaceutical Medicine of the Royal Colleges of Physicians U.K.,
said, “It is increasingly clear that the complexity in treating
COVID-19 pneumonia relates to its impact on multiple
pro-inflammatory pathways. For an effective treatment, we need a
broad acting anti-inflammatory and the fact that nomacopan has been
shown in clinical trials to inhibit the pathways that underpin this
severe devastating disease creates a promising platform for its
current clinical investigation.”
- Ramlall, et al., Immune complement and coagulation dysfunction
in adverse outcomes of SARS-CoV-2 infection, 2020
- Merrill, et al., Emerging evidence of a COVID-19 thrombotic
syndrome has treatment implications, 2020
- Funk, et al., A Novel Strategy to Mitigate the
Hyperinflammatory Response to COVID-19 by Targeting Leukotrienes,
2020
- Huber-Lang, et al., Double Blockade of CD14 and Complement C5
Abolishes the Cytokine Storm and Improves Morbidity and Survival in
Polymicrobial Sepsis in Mice, 2014
- Mehta P, et al., COVID-19: consider cytokine storm syndromes
and immunosuppression, 2020
- Garcia, et al., Complement C5 Activation during Influenza A
Infection in Mice Contributes to Neutrophil Recruitment and Lung
Injury, 2013
- Roversi, et al., Bifunctional Lipocalin Ameliorates Murine
Immune complex-induced Acute Lung Injury, 2013
Conference call and webcast
Akari will host a conference call and webcast today, August 31,
2020, at 8:30 a.m. EDT (1:30 p.m. BST). The conference call may be
accessed by dialing (844) 461-9933 (Toll-Free) or (636) 812-6633
(international) using the conference ID 2469894. The webcast can be
accessed live via the Investor Relations section of the Akari
website at http://investor.akaritx.com/news-and-events/events.
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 (formerly known as Coversin), is a C5
complement inhibitor that also independently and specifically
inhibits leukotriene B4 (LTB4) activity.
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. You should not
place undue reliance upon the Company’s forward looking statements.
Except as required by law, the Company undertakes no obligation to
revise or update any forward-looking statements in order to reflect
any event or circumstance that may arise after the date of this
press release. 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 U.S. 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 and
any other product candidates, which may result in unexpected cost
expenditures; our ability to successfully develop nomacopan as a
treatment for COVID-19 related pneumonia and to successfully
commercialize any product in that indication; our ability to obtain
orphan drug designation in additional indications; risks inherent
in drug development in general and risks specific to the
development of potential treatments for COVID-19 related illnesses;
uncertainties in obtaining successful clinical results for
nomacopan and any other product candidates and unexpected costs
that may result therefrom; difficulties enrolling patients in our
clinical trials; our ability to enter into collaborative,
licensing, and other commercial relationships and on terms
commercially reasonable to U.S.; failure to realize any value of
nomacopan 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 may not be as large as
expected; risks associated with the impact of the outbreak of
coronavirus; 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 US 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.
Investor Contact:
Peter Vozzo Westwicke +1 (443) 213-0505
peter.vozzo@westwicke.com
Media Contact:
Sukaina Virji / Lizzie Seeley Consilium Strategic
Communications +44 (0)20 3709 5700 Akari@consilium-comms.com
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